{"entity": "publications", "timestamp": "2026-06-07T10:42:58.127Z", "year": "2020", "links": {"self": {"href": "https://publications.scilifelab.se/publications/2020.json"}, "display": {"href": "https://publications.scilifelab.se/publications/2020"}}, "publications_count": 640, "full": true, "publications": [{"entity": "publication", "iuid": "ccdbb2999539431788b8756ce0867a5e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ccdbb2999539431788b8756ce0867a5e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ccdbb2999539431788b8756ce0867a5e"}}, "title": "Whole-genome sequencing of recurrent neuroblastoma reveals somatic mutations that affect key players in cancer progression and telomere maintenance.", "authors": [{"family": "Fransson", "given": "Susanne", "initials": "S"}, {"family": "Martinez-Monleon", "given": "Angela", "initials": "A"}, {"family": "Johansson", "given": "Mathias", "initials": "M"}, {"family": "Sj\u00f6berg", "given": "Rose-Marie", "initials": "RM"}, {"family": "Bj\u00f6rklund", "given": "Caroline", "initials": "C"}, {"family": "Ljungman", "given": "Gustaf", "initials": "G"}, {"family": "Ek", "given": "Torben", "initials": "T"}, {"family": "Kogner", "given": "Per", "initials": "P"}, {"family": "Martinsson", "given": "Tommy", "initials": "T"}], "type": "journal article", "published": "2020-12-31", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "22432", "issn-l": "2045-2322"}, "abstract": "Neuroblastoma is the most common and deadly childhood tumor. Relapsed or refractory neuroblastoma has a very poor prognosis despite recent treatment advances. To investigate genomic alterations associated with relapse and therapy resistance, whole-genome sequencing was performed on diagnostic and relapsed lesions together with constitutional DNA from seven children. Sequencing of relapsed tumors indicates somatic alterations in diverse genes, including those involved in RAS-MAPK signaling, promoting cell cycle progression or function in telomere maintenance and immortalization. Among recurrent alterations, CCND1-gain, TERT-rearrangements, and point mutations in POLR2A, CDK5RAP, and MUC16 were shown in \u2265 2 individuals. Our cohort contained examples of converging genomic alterations in primary-relapse tumor pairs, indicating dependencies related to specific genetic lesions. We also detected rare genetic germline variants in DNA repair genes (e.g., BARD1, BRCA2, CHEK2, and WRN) that might cooperate with somatically acquired variants in these patients with highly aggressive recurrent neuroblastoma. Our data indicate the importance of monitoring recurrent neuroblastoma through sequential genomic characterization and that new therapeutic approaches combining the targeting of MAPK signaling, cell cycle progression, and telomere activity are required for this challenging patient group.", "doi": "10.1038/s41598-020-78370-7", "pmid": "33384420", "labels": {"Clinical Genomics Gothenburg": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-78370-7"}, {"db": "pmc", "key": "PMC7775426"}], "notes": [], "created": "2022-03-29T13:38:03.020Z", "modified": "2022-03-29T13:38:03.033Z"}, {"entity": "publication", "iuid": "2ccf73357b4b4ad5b3707f15305d5f7a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2ccf73357b4b4ad5b3707f15305d5f7a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2ccf73357b4b4ad5b3707f15305d5f7a"}}, "title": "Lysophospholipids as Predictive Markers of ST-Elevation Myocardial Infarction (STEMI) and Non-ST-Elevation Myocardial Infarction (NSTEMI).", "authors": [{"family": "Chorell", "given": "Elin", "initials": "E", "orcid": "0000-0003-2523-1940", "researcher": {"href": "https://publications.scilifelab.se/researcher/ada783ae0a824621a3b8e1024aae13a4.json"}}, {"family": "Olsson", "given": "Tommy", "initials": "T", "orcid": "0000-0001-7768-1076", "researcher": {"href": "https://publications.scilifelab.se/researcher/9405d6c9f3964f0d8e19cf1c60c2650b.json"}}, {"family": "Jansson", "given": "Jan-H\u00e5kan", "initials": "JH"}, {"family": "Wennberg", "given": "Patrik", "initials": "P"}], "type": "journal article", "published": "2020-12-31", "journal": {"title": "Metabolites", "issn": "2218-1989", "volume": "11", "issue": "1", "pages": "25", "issn-l": null}, "abstract": "The present study explored patterns of circulating metabolites and proteins that can predict future risk for ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI). We conducted a prospective nested case-control study in northern Sweden in individuals who developed STEMI (N = 50) and NSTEMI (N = 50) within 5 years and individually matched controls (N = 100). Fasted plasma samples were subjected to multiplatform mass spectrometry-based metabolomics and multiplex protein analyses. Multivariate analyses were used to elucidate infarction-specific metabolite and protein risk profiles associated with future incident STEMI and NSTEMI. We found that altered lysophosphatidylcholine (LPC) to lysophosphatidylethanolamine (LPE) ratio predicted STEMI and NSTEMI events in different ways. In STEMI, lysophospholipids (mainly LPEs) were lower, whereas in NSTEMI, lysophospholipids (mainly LPEs) were higher. We found a similar response for all detected lysophospholipids but significant alterations only for those containing linoleic acid (C18:2, p < 0.05). Patients with STEMI had higher secretoglobin family 3A member 2 and tartrate-resistant acid phosphate type 5 and lower platelet-derived growth factor subunit A, which are proteins associated with atherosclerosis severity and plaque development mediated via altered phospholipid metabolism. In contrast, patients with NSTEMI had higher levels of proteins associated with inflammation and macrophage activation, including interleukin 6, C-reactive protein, chemerin, and cathepsin X and D. The STEMI risk marker profile includes factors closely related to the development of unstable plaque, including a higher LPC:LPE ratio, whereas NSTEMI is characterized by a lower LPC:LPE ratio and increased inflammation.", "doi": "10.3390/metabo11010025", "pmid": "33396480", "labels": {"Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pii", "key": "metabo11010025"}, {"db": "pmc", "key": "PMC7823877"}], "notes": [], "created": "2021-01-12T12:46:47.111Z", "modified": "2025-10-17T13:03:16.444Z"}, {"entity": "publication", "iuid": "68b97a92c535461cb6c041f6d14df2d1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/68b97a92c535461cb6c041f6d14df2d1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/68b97a92c535461cb6c041f6d14df2d1"}}, "title": "Defining eligible patients for allele-selective chemotherapies targeting NAT2 in colorectal cancer.", "authors": [{"family": "Rendo", "given": "Veronica", "initials": "V"}, {"family": "Kundu", "given": "Snehangshu", "initials": "S"}, {"family": "Rameika", "given": "Natallia", "initials": "N"}, {"family": "Ljungstr\u00f6m", "given": "Viktor", "initials": "V"}, {"family": "Svensson", "given": "Richard", "initials": "R"}, {"family": "Palin", "given": "Kimmo", "initials": "K"}, {"family": "Aaltonen", "given": "Lauri", "initials": "L"}, {"family": "Stoimenov", "given": "Ivaylo", "initials": "I"}, {"family": "Sj\u00f6blom", "given": "Tobias", "initials": "T"}], "type": "journal article", "published": "2020-12-31", "journal": {"title": "Sci Rep", "issn": "2045-2322", "issn-l": "2045-2322", "volume": "10", "issue": "1", "pages": "22436"}, "abstract": "Therapies targeting somatic bystander genetic events represent a new avenue for cancer treatment. We recently identified a subset of colorectal cancer (CRC) patients who are heterozygous for a wild-type and a low activity allele (NAT2*6) but lack the wild-type allele in their tumors due to loss of heterozygosity (LOH) at 8p22. These tumors were sensitive to treatment with a cytotoxic substrate of NAT2 (6-(4-aminophenyl)-N-(3,4,5-trimethoxyphenyl)pyrazin-2-amine, APA), and pointed to NAT2 loss being a therapeutically exploitable vulnerability of CRC tumors. To better estimate the total number of treatable CRC patients, we here determined whether tumor cells retaining also other NAT2 low activity variants after LOH respond to APA treatment. The prevalent low activity alleles NAT2*5 and NAT2*14, but not NAT2*7, were found to be low metabolizers with high sensitivity to APA. By analysis of two different CRC patient cohorts, we detected heterozygosity for NAT2 alleles targetable by APA, along with allelic imbalances pointing to LOH, in ~ 24% of tumors. Finally, to haplotype the NAT2 locus in tumor and patient-matched normal samples in a clinical setting, we develop and demonstrate a long-read sequencing based assay. In total, > 79.000 CRC patients per year fulfil genetic criteria for high sensitivity to a NAT2 LOH therapy and their eligibility can be assessed by clinical sequencing.", "doi": "10.1038/s41598-020-80288-z", "pmid": "33384440", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-80288-z"}, {"db": "pmc", "key": "PMC7775439"}], "notes": [], "created": "2021-01-08T12:11:29.314Z", "modified": "2024-01-16T13:48:41.098Z"}, {"entity": "publication", "iuid": "6878fad3e80b4b2d84ef0cf49160ba6b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6878fad3e80b4b2d84ef0cf49160ba6b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6878fad3e80b4b2d84ef0cf49160ba6b"}}, "title": "Mechanistic Insights into Regulation of the ALC1 Remodeler by the Nucleosome Acidic Patch.", "authors": [{"family": "Lehmann", "given": "Laura C", "initials": "LC", "orcid": "0000-0003-2518-5606", "researcher": {"href": "https://publications.scilifelab.se/researcher/e73ae6d30ebe4c68971f3b0908d061c6.json"}}, {"family": "Bacic", "given": "Luka", "initials": "L", "orcid": "0000-0001-6896-3506", "researcher": {"href": "https://publications.scilifelab.se/researcher/0bcd56cafd294116870c894ba344cf12.json"}}, {"family": "Hewitt", "given": "Graeme", "initials": "G"}, {"family": "Brackmann", "given": "Klaus", "initials": "K"}, {"family": "Sabantsev", "given": "Anton", "initials": "A", "orcid": "0000-0002-8559-8894", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae73150df15e4730be688fc5137a1389.json"}}, {"family": "Gaullier", "given": "Guillaume", "initials": "G", "orcid": "0000-0003-3405-6021", "researcher": {"href": "https://publications.scilifelab.se/researcher/26bde2020c164cff8216338fb2d6d652.json"}}, {"family": "Pytharopoulou", "given": "Sofia", "initials": "S"}, {"family": "Degliesposti", "given": "Gianluca", "initials": "G"}, {"family": "Okkenhaug", "given": "Hanneke", "initials": "H"}, {"family": "Tan", "given": "Song", "initials": "S"}, {"family": "Costa", "given": "Alessandro", "initials": "A"}, {"family": "Skehel", "given": "J Mark", "initials": "JM"}, {"family": "Boulton", "given": "Simon J", "initials": "SJ", "orcid": "0000-0001-6936-6834", "researcher": {"href": "https://publications.scilifelab.se/researcher/8be210bb12b54a19b4020803fa0c3357.json"}}, {"family": "Deindl", "given": "Sebastian", "initials": "S", "orcid": "0000-0001-6807-8654", "researcher": {"href": "https://publications.scilifelab.se/researcher/2e45e8288a3445e2b346f29b73141738.json"}}], "type": "journal article", "published": "2020-12-22", "journal": {"title": "Cell Rep", "issn": "2211-1247", "issn-l": null, "volume": "33", "issue": "12", "pages": "108529"}, "abstract": "Upon DNA damage, the ALC1/CHD1L nucleosome remodeling enzyme (remodeler) is activated by binding to poly(ADP-ribose). How activated ALC1 recognizes the nucleosome, as well as how this recognition is coupled to remodeling, is unknown. Here, we show that remodeling by ALC1 requires a wild-type acidic patch on the entry side of the nucleosome. The cryo-electron microscopy structure of a nucleosome-ALC1 linker complex reveals a regulatory linker segment that binds to the acidic patch. Mutations within this interface alter the dynamics of ALC1 recruitment to DNA damage and impede the ATPase and remodeling activities of ALC1. Full activation requires acidic patch-linker segment interactions that tether the remodeler to the nucleosome and couple ATP hydrolysis to nucleosome mobilization. Upon DNA damage, such a requirement may be used to modulate ALC1 activity via changes in the nucleosome acidic patches.", "doi": "10.1016/j.celrep.2020.108529", "pmid": "33357431", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pii", "key": "S2211-1247(20)31518-7"}, {"db": "pmc", "key": "PMC7116876"}, {"db": "mid", "key": "EMS117809"}], "notes": [], "created": "2021-03-16T07:24:16.174Z", "modified": "2023-12-04T10:15:55.187Z"}, {"entity": "publication", "iuid": "08437ea506ac46a5ac92c90dc3eb5eb7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/08437ea506ac46a5ac92c90dc3eb5eb7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/08437ea506ac46a5ac92c90dc3eb5eb7"}}, "title": "Genomic Adaptations and Evolutionary History of the Extinct Scimitar-Toothed Cat, Homotherium latidens.", "authors": [{"family": "Barnett", "given": "Ross", "initials": "R"}, {"family": "Westbury", "given": "Michael V", "initials": "MV"}, {"family": "Sandoval-Velasco", "given": "Marcela", "initials": "M"}, {"family": "Vieira", "given": "Filipe Garrett", "initials": "FG"}, {"family": "Jeon", "given": "Sungwon", "initials": "S"}, {"family": "Zazula", "given": "Grant", "initials": "G"}, {"family": "Martin", "given": "Michael D", "initials": "MD"}, {"family": "Ho", "given": "Simon Y W", "initials": "SYW"}, {"family": "Mather", "given": "Niklas", "initials": "N"}, {"family": "Gopalakrishnan", "given": "Shyam", "initials": "S"}, {"family": "Ramos-Madrigal", "given": "Jazm\u00edn", "initials": "J"}, {"family": "de Manuel", "given": "Marc", "initials": "M"}, {"family": "Zepeda-Mendoza", "given": "M Lisandra", "initials": "ML"}, {"family": "Antunes", "given": "Agostinho", "initials": "A"}, {"family": "Baez", "given": "Aldo Carmona", "initials": "AC"}, {"family": "De Cahsan", "given": "Binia", "initials": "B"}, {"family": "Larson", "given": "Greger", "initials": "G"}, {"family": "O'Brien", "given": "Stephen J", "initials": "SJ"}, {"family": "Eizirik", "given": "Eduardo", "initials": "E"}, {"family": "Johnson", "given": "Warren E", "initials": "WE"}, {"family": "Koepfli", "given": "Klaus-Peter", "initials": "KP", "orcid": "0000-0001-7281-0676", "researcher": {"href": "https://publications.scilifelab.se/researcher/178cb44eedd74528a956ad645fe3aa16.json"}}, {"family": "Wilting", "given": "Andreas", "initials": "A"}, {"family": "Fickel", "given": "J\u00f6rns", "initials": "J"}, {"family": "Dal\u00e9n", "given": "Love", "initials": "L", "orcid": "0000-0001-8270-7613", "researcher": {"href": "https://publications.scilifelab.se/researcher/48ecf726779249ac9d12f4f7a1cc62bf.json"}}, {"family": "Lorenzen", "given": "Eline D", "initials": "ED"}, {"family": "Marques-Bonet", "given": "Tomas", "initials": "T"}, {"family": "Hansen", "given": "Anders J", "initials": "AJ"}, {"family": "Zhang", "given": "Guojie", "initials": "G"}, {"family": "Bhak", "given": "Jong", "initials": "J"}, {"family": "Yamaguchi", "given": "Nobuyuki", "initials": "N"}, {"family": "Gilbert", "given": "M Thomas P", "initials": "MTP"}], "type": "journal article", "published": "2020-12-21", "journal": {"title": "Curr. Biol.", "issn": "1879-0445", "volume": "30", "issue": "24", "pages": "5018-5025.e5", "issn-l": "0960-9822"}, "abstract": "Homotherium was a genus of large-bodied scimitar-toothed cats, morphologically distinct from any extant felid species, that went extinct at the end of the Pleistocene [1-4]. They possessed large, saber-form serrated canine teeth, powerful forelimbs, a sloping back, and an enlarged optic bulb, all of which were key characteristics for predation on Pleistocene megafauna [5]. Previous mitochondrial DNA phylogenies suggested that it was a highly divergent sister lineage to all extant cat species [6-8]. However, mitochondrial phylogenies can be misled by hybridization [9], incomplete lineage sorting (ILS), or sex-biased dispersal patterns [10], which might be especially relevant for Homotherium since widespread mito-nuclear discrepancies have been uncovered in modern cats [10]. To examine the evolutionary history of Homotherium, we generated a \u223c7x nuclear genome and a \u223c38x exome from H. latidens using shotgun and target-capture sequencing approaches. Phylogenetic analyses reveal Homotherium as highly divergent (\u223c22.5 Ma) from living cat species, with no detectable signs of gene flow. Comparative genomic analyses found signatures of positive selection in several genes, including those involved in vision, cognitive function, and energy consumption, putatively consistent with diurnal activity, well-developed social behavior, and cursorial hunting [5]. Finally, we uncover relatively high levels of genetic diversity, suggesting that Homotherium may have been more abundant than the limited fossil record suggests [3, 4, 11-14]. Our findings complement and extend previous inferences from both the fossil record and initial molecular studies, enhancing our understanding of the evolution and ecology of this remarkable lineage.", "doi": "10.1016/j.cub.2020.09.051", "pmid": "33065008", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service"}, "xrefs": [{"db": "pii", "key": "S0960-9822(20)31421-4"}, {"db": "pmc", "key": "PMC7762822"}], "notes": [], "created": "2020-12-07T16:36:46.792Z", "modified": "2023-06-19T11:45:34.625Z"}, {"entity": "publication", "iuid": "f046cb0689f843a8833a93b6acea2080", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f046cb0689f843a8833a93b6acea2080.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f046cb0689f843a8833a93b6acea2080"}}, "title": "You Had Me at \u201cMAGIC\u201d!: Four Barley MAGIC Populations Reveal Novel Resistance QTL for Powdery Mildew", "authors": [{"family": "Novakazi", "given": "Flutur\u00eb", "initials": "F", "orcid": "0000-0001-7151-6811", "researcher": {"href": "https://publications.scilifelab.se/researcher/5812b915262d44e4972483c8314675c3.json"}}, {"family": "Krusell", "given": "Lene", "initials": "L"}, {"family": "Jensen", "given": "Jens", "initials": "J"}, {"family": "Orabi", "given": "Jihad", "initials": "J", "orcid": "0000-0001-9641-6657", "researcher": {"href": "https://publications.scilifelab.se/researcher/ec5965b7edd0413791c990a978f17045.json"}}, {"family": "Jahoor", "given": "Ahmed", "initials": "A"}, {"family": "Bengtsson", "given": "Ther\u00e9se", "initials": "T", "orcid": "0000-0003-4784-1723", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ec4d4a00bcf4fd59113eb264283b92a.json"}}, {"family": null, "given": "", "initials": ""}], "type": "journal-article", "published": "2020-12-18", "journal": {"title": "Genes", "issn": "2073-4425", "issn-l": "2073-4425", "volume": "11", "issue": "12", "pages": "1512"}, "abstract": "Blumeria graminis f. sp. hordei (Bgh), the causal agent of barley powdery mildew (PM), is one of the most important barley leaf diseases and is prevalent in most barley growing regions. Infection decreases grain quality and yields on average by 30%. Multi-parent advanced generation inter-cross (MAGIC) populations combine the advantages of bi-parental and association panels and offer the opportunity to incorporate exotic alleles into adapted material. Here, four barley MAGIC populations consisting of six to eight founders were tested for PM resistance in field trials in Denmark. Principle component and STRUCTURE analysis showed the populations were unstructured and genome-wide linkage disequilibrium (LD) decay varied between 14 and 38 Mbp. Genome-wide association studies (GWAS) identified 11 regions associated with PM resistance located on chromosomes 1H, 2H, 3H, 4H, 5H and 7H, of which three regions are putatively novel resistance quantitative trait locus/loci (QTL). For all regions high-confidence candidate genes were identified that are predicted to be involved in pathogen defense. Haplotype analysis of the significant SNPs revealed new allele combinations not present in the founders and associated with high resistance levels.", "doi": "10.3390/genes11121512", "pmid": "33352820", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7766815"}, {"db": "pii", "key": "genes11121512"}], "notes": [], "created": "2020-12-28T17:52:37.985Z", "modified": "2023-06-19T11:38:46.230Z"}, {"entity": "publication", "iuid": "976e52a6a98747bfa09f48511cc06e09", "links": {"self": {"href": "https://publications.scilifelab.se/publication/976e52a6a98747bfa09f48511cc06e09.json"}, "display": {"href": "https://publications.scilifelab.se/publication/976e52a6a98747bfa09f48511cc06e09"}}, "title": "Depletion of protein kinase STK25 ameliorates renal lipotoxicity and protects against diabetic kidney disease.", "authors": [{"family": "Cansby", "given": "Emmelie", "initials": "E"}, {"family": "Caputo", "given": "Mara", "initials": "M"}, {"family": "Gao", "given": "Lei", "initials": "L"}, {"family": "Kulkarni", "given": "Nagaraj M", "initials": "NM"}, {"family": "Nerstedt", "given": "Annika", "initials": "A"}, {"family": "St\u00e5hlman", "given": "Marcus", "initials": "M"}, {"family": "Bor\u00e9n", "given": "Jan", "initials": "J"}, {"family": "Porosk", "given": "Rando", "initials": "R"}, {"family": "Soomets", "given": "Ursel", "initials": "U"}, {"family": "Pedrelli", "given": "Matteo", "initials": "M"}, {"family": "Parini", "given": "Paolo", "initials": "P"}, {"family": "Marschall", "given": "Hanns-Ulrich", "initials": "HU"}, {"family": "Nystr\u00f6m", "given": "Jenny", "initials": "J"}, {"family": "Howell", "given": "Brian W", "initials": "BW"}, {"family": "Mahlapuu", "given": "Margit", "initials": "M"}], "type": "journal article", "published": "2020-12-17", "journal": {"title": "JCI Insight", "issn": "2379-3708", "volume": "5", "issue": "24", "issn-l": "2379-3708"}, "abstract": "Diabetic kidney disease (DKD) is the most common cause of severe renal disease worldwide and the single strongest predictor of mortality in diabetes patients. Kidney steatosis has emerged as a critical trigger in the pathogenesis of DKD; however, the molecular mechanism of renal lipotoxicity remains largely unknown. Our recent studies in genetic mouse models, human cell lines, and well-characterized patient cohorts have identified serine/threonine protein kinase 25 (STK25) as a critical regulator of ectopic lipid storage in several metabolic organs prone to diabetic damage. Here, we demonstrate that overexpression of STK25 aggravates renal lipid accumulation and exacerbates structural and functional kidney injury in a mouse model of DKD. Reciprocally, inhibiting STK25 signaling in mice ameliorates diet-induced renal steatosis and alleviates the development of DKD-associated pathologies. Furthermore, we find that STK25 silencing in human kidney cells protects against lipid deposition, as well as oxidative and endoplasmic reticulum stress. Together, our results suggest that STK25 regulates a critical node governing susceptibility to renal lipotoxicity and that STK25 antagonism could mitigate DKD progression.", "doi": "10.1172/jci.insight.140483", "pmid": "33170807", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7819747"}, {"db": "pii", "key": "140483"}], "notes": [], "created": "2023-02-16T08:05:50.037Z", "modified": "2023-02-16T08:05:50.051Z"}, {"entity": "publication", "iuid": "95f1d478c59c4366bc3dbf6010d97d4d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/95f1d478c59c4366bc3dbf6010d97d4d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/95f1d478c59c4366bc3dbf6010d97d4d"}}, "title": "A biomimetic engineered bone platform for advanced testing of prosthetic implants.", "authors": [{"family": "Sladkova-Faure", "given": "Martina", "initials": "M"}, {"family": "Pujari-Palmer", "given": "Michael", "initials": "M"}, {"family": "\u00d6hman-M\u00e4gi", "given": "Caroline", "initials": "C"}, {"family": "L\u00f3pez", "given": "Alejandro", "initials": "A"}, {"family": "Wang", "given": "Hanbin", "initials": "H"}, {"family": "Engqvist", "given": "H\u00e5kan", "initials": "H"}, {"family": "de Peppo", "given": "Giuseppe Maria", "initials": "GM"}], "type": "journal article", "published": "2020-12-17", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "22154", "issn-l": "2045-2322"}, "abstract": "Existing methods for testing prosthetic implants suffer from critical limitations, creating an urgent need for new strategies that facilitate research and development of implants with enhanced osseointegration potential. Herein, we describe a novel, biomimetic, human bone platform for advanced testing of implants in vitro, and demonstrate the scientific validity and predictive value of this approach using an assortment of complementary evaluation methods. We anchored titanium (Ti) and stainless steel (SS) implants into biomimetic scaffolds, seeded with human induced mesenchymal stem cells, to recapitulate the osseointegration process in vitro. We show distinct patterns of gene expression, matrix deposition, and mineralization in response to the two materials, with Ti implants ultimately resulting in stronger integration strength, as seen in other preclinical and clinical studies. Interestingly, RNAseq analysis reveals that the TGF-beta and the FGF2 pathways are overexpressed in response to Ti implants, while the Wnt, BMP, and IGF pathways are overexpressed in response to SS implants. High-resolution imaging shows significantly increased tissue mineralization and calcium deposition at the tissue-implant interface in response to Ti implants, contributing to a twofold increase in pullout strength compared to SS implants. Our technology creates unprecedented research opportunities towards the design of implants and biomaterials that can be personalized, and exhibit enhanced osseointegration potential, with reduced need for animal testing.", "doi": "10.1038/s41598-020-78416-w", "pmid": "33335113", "labels": {"Bioinformatics Support, Infrastructure and Training": "Service", "Bioinformatics Support and Infrastructure": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7747643"}, {"db": "pii", "key": "10.1038/s41598-020-78416-w"}], "notes": [], "created": "2022-11-25T08:01:42.131Z", "modified": "2022-11-25T08:01:42.135Z"}, {"entity": "publication", "iuid": "939dd69f5a994bca89eeedabd916b7dd", "links": {"self": {"href": "https://publications.scilifelab.se/publication/939dd69f5a994bca89eeedabd916b7dd.json"}, "display": {"href": "https://publications.scilifelab.se/publication/939dd69f5a994bca89eeedabd916b7dd"}}, "title": "The Bactericidal Fatty Acid Mimetic 2CCA-1 Selectively Targets Pneumococcal Extracellular Polyunsaturated Fatty Acid Metabolism.", "authors": [{"family": "Reithuber", "given": "Elisabeth", "initials": "E"}, {"family": "Nannapaneni", "given": "Priyanka", "initials": "P"}, {"family": "Rzhepishevska", "given": "Olena", "initials": "O"}, {"family": "Lindgren", "given": "Anders E G", "initials": "AEG"}, {"family": "Ilchenko", "given": "Oleksandr", "initials": "O"}, {"family": "Normark", "given": "Staffan", "initials": "S"}, {"family": "Almqvist", "given": "Fredrik", "initials": "F"}, {"family": "Henriques-Normark", "given": "Birgitta", "initials": "B"}, {"family": "Mellroth", "given": "Peter", "initials": "P"}], "type": "journal article", "published": "2020-12-15", "journal": {"title": "MBio", "issn": "2150-7511", "volume": "11", "issue": "6", "pages": "e03027-20", "issn-l": null}, "abstract": "Streptococcus pneumoniae, a major cause of pneumonia, sepsis, and meningitis worldwide, has the nasopharynges of small children as its main ecological niche. Depletion of pneumococci from this niche would reduce the disease burden and could be achieved using small molecules with narrow-spectrum antibacterial activity. We identified the alkylated dicyclohexyl carboxylic acid 2CCA-1 as a potent inducer of autolysin-mediated lysis of S. pneumoniae, while having low activity against Staphylococcus aureus 2CCA-1-resistant strains were found to have inactivating mutations in fakB3, known to be required for uptake of host polyunsaturated fatty acids, as well as through inactivation of the transcriptional regulator gene fabT, vital for endogenous, de novo fatty acid synthesis regulation. Structure activity relationship exploration revealed that, besides the central dicyclohexyl group, the fatty acid-like structural features of 2CCA-1 were essential for its activity. The lysis-inducing activity of 2CCA-1 was considerably more potent than that of free fatty acids and required growing bacteria, suggesting that 2CCA-1 needs to be metabolized to exert its antimicrobial activity. Total lipid analysis of 2CCA-1 treated bacteria identified unique masses that were modeled to 2CCA-1 containing lysophosphatidic and phosphatidic acid in wild-type but not in fakB3 mutant bacteria. This suggests that 2CCA-1 is metabolized as a fatty acid via FakB3 and utilized as a phospholipid building block, leading to accumulation of toxic phospholipid species. Analysis of FabT-mediated fakB3 expression elucidates how the pneumococcus could ensure membrane homeostasis and concurrent economic use of host-derived fatty acids.IMPORTANCE Fatty acid biosynthesis is an attractive antibiotic target, as it affects the supply of membrane phospholipid building blocks. In Streptococcus pneumoniae, it is not sufficient to target only the endogenous fatty acid synthesis machinery, as uptake of host fatty acids may bypass this inhibition. Here, we describe a small-molecule compound, 2CCA-1, with potent bactericidal activity that upon interactions with the fatty acid binding protein FakB3, which is present in a limited number of Gram-positive species, becomes metabolized and incorporated as a toxic phospholipid species. Resistance to 2CCA-1 developed specifically in fakB3 and the regulatory gene fabT These mutants reveal a regulatory connection between the extracellular polyunsaturated fatty acid metabolism and endogenous fatty acid synthesis in S. pneumoniae, which could ensure balance between efficient scavenging of host polyunsaturated fatty acids and membrane homeostasis. The data might be useful in the identification of narrow-spectrum treatment strategies to selectively target members of the Lactobacillales such as S. pneumoniae.", "doi": "10.1128/mBio.03027-20", "pmid": "33323510", "labels": {"Bioinformatics Support for Computational Resources": "Service", "Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pii", "key": "mBio.03027-20"}, {"db": "pmc", "key": "PMC7773995"}], "notes": [], "created": "2021-01-12T12:46:51.617Z", "modified": "2025-10-17T13:03:16.455Z"}, {"entity": "publication", "iuid": "295b747fc040459084e737814f8a3f09", "links": {"self": {"href": "https://publications.scilifelab.se/publication/295b747fc040459084e737814f8a3f09.json"}, "display": {"href": "https://publications.scilifelab.se/publication/295b747fc040459084e737814f8a3f09"}}, "title": "Structure and elevator mechanism of the mammalian sodium/proton exchanger NHE9.", "authors": [{"family": "Winklemann", "given": "Iven", "initials": "I"}, {"family": "Matsuoka", "given": "Rei", "initials": "R"}, {"family": "Meier", "given": "Pascal F", "initials": "PF"}, {"family": "Shutin", "given": "Denis", "initials": "D"}, {"family": "Zhang", "given": "Chenou", "initials": "C"}, {"family": "Orellana", "given": "Laura", "initials": "L"}, {"family": "Sexton", "given": "Ricky", "initials": "R"}, {"family": "Landreh", "given": "Michael", "initials": "M", "orcid": "0000-0002-7958-4074", "researcher": {"href": "https://publications.scilifelab.se/researcher/87494f4204c04be9bce5e9ddcdc92d8a.json"}}, {"family": "Robinson", "given": "Carol V", "initials": "CV"}, {"family": "Beckstein", "given": "Oliver", "initials": "O"}, {"family": "Drew", "given": "David", "initials": "D", "orcid": "0000-0001-8866-6349", "researcher": {"href": "https://publications.scilifelab.se/researcher/cc19844f8147480fb0af2e437744131b.json"}}], "type": "journal article", "published": "2020-12-15", "journal": {"title": "EMBO J.", "issn": "1460-2075", "volume": "39", "issue": "24", "pages": "e105908", "issn-l": "0261-4189"}, "abstract": "Na+ /H+ exchangers (NHEs) are ancient membrane-bound nanomachines that work to regulate intracellular pH, sodium levels and cell volume. NHE activities contribute to the control of the cell cycle, cell proliferation, cell migration and vesicle trafficking. NHE dysfunction has been linked to many diseases, and they are targets of pharmaceutical drugs. Despite their fundamental importance to cell homeostasis and human physiology, structural information for the mammalian NHE was lacking. Here, we report the cryogenic electron microscopy structure of NHE isoform 9 (SLC9A9) from Equus caballus at 3.2 \u00c5 resolution, an endosomal isoform highly expressed in the brain and associated with autism spectrum (ASD) and attention deficit hyperactivity (ADHD) disorders. Despite low sequence identity, the NHE9 architecture and ion-binding site are remarkably similar to distantly related bacterial Na+ /H+ antiporters with 13 transmembrane segments. Collectively, we reveal the conserved architecture of the NHE ion-binding site, their elevator-like structural transitions, the functional implications of autism disease mutations and the role of phosphoinositide lipids to promote homodimerization that, together, have important physiological ramifications.", "doi": "10.15252/embj.2020105908", "pmid": "33118634", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7737618"}, {"db": "PDB", "key": "6Z3Z"}, {"db": "PDB", "key": "6Z3Y"}], "notes": [], "created": "2020-10-29T17:09:30.112Z", "modified": "2021-11-10T12:44:05.204Z"}, {"entity": "publication", "iuid": "ea97044dbd2c4ef6bda8a7fba723e33c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ea97044dbd2c4ef6bda8a7fba723e33c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ea97044dbd2c4ef6bda8a7fba723e33c"}}, "title": "Screening of Multiple Biomarkers Associated With Ischemic Stroke in Atrial Fibrillation.", "authors": [{"family": "Hijazi", "given": "Ziad", "initials": "Z"}, {"family": "Wallentin", "given": "Lars", "initials": "L"}, {"family": "Lindb\u00e4ck", "given": "Johan", "initials": "J"}, {"family": "Alexander", "given": "John H", "initials": "JH"}, {"family": "Connolly", "given": "Stuart J", "initials": "SJ"}, {"family": "Eikelboom", "given": "John W", "initials": "JW"}, {"family": "Ezekowitz", "given": "Michael D", "initials": "MD"}, {"family": "Granger", "given": "Christopher B", "initials": "CB"}, {"family": "Lopes", "given": "Renato D", "initials": "RD"}, {"family": "Pol", "given": "Tymon", "initials": "T"}, {"family": "Yusuf", "given": "Salim", "initials": "S"}, {"family": "Oldgren", "given": "Jonas", "initials": "J"}, {"family": "Siegbahn", "given": "Agneta", "initials": "A"}], "type": "clinical trial", "published": "2020-12-15", "journal": {"title": "J Am Heart Assoc", "issn": "2047-9980", "volume": "9", "issue": "24", "pages": "e018984", "issn-l": "2047-9980"}, "abstract": "Background To explore the pathophysiological features of ischemic stroke in patients with atrial fibrillation (AF), we evaluated the association between 268 plasma proteins and subsequent ischemic stroke in 2 large AF cohorts receiving oral anticoagulation. Methods and Results A case-cohort sample of patients with AF from the ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) trial, including 282 cases with ischemic stroke or systemic embolism and a random sample of 4124 without these events, during 1.9 years of follow-up was used for identification. Validation was provided by a similar case-cohort sample of patients with AF from the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) trial, including 149 cases with ischemic stroke/systemic embolism and a random sample of 1062 without these events. In plasma obtained before randomization, 268 unique biomarkers were measured with OLINK proximity extension assay panels (CVD II, CVD III, and Inflammation) and conventional immunoassays. The association between biomarkers and outcomes was evaluated by random survival forest and adjusted Cox regression. According to random survival forest or Cox regression analyses, the biomarkers most strongly and consistently associated with ischemic stroke/systemic embolism were matrix metalloproteinase-9, NT-proBNP (N-terminal pro-B-type natriuretic peptide), osteopontin, sortilin, soluble suppression of tumorigenesis 2, and trefoil factor-3. The corresponding hazard ratios (95% CIs) for an interquartile difference were as follows: 1.18 (1.00-1.38), 1.55 (1.28-1.88), 1.28 (1.07-1.53), 1.19 (1.02-1.39), 1.23 (1.05-1.45), and 1.19 (0.97-1.45), respectively. Conclusions In patients with AF, of 268 unique biomarkers, the 6 biomarkers most strongly associated with subsequent ischemic stroke/systemic embolism represent fibrosis/remodeling (matrix metalloproteinase-9 and soluble suppression of tumorigenesis 2), cardiac dysfunction (NT-proBNP), vascular calcification (osteopontin), metabolism (sortilin), and mucosal integrity/ischemia (trefoil factor-3). Registration URL: https://www.clinicaltrials.gov. Unique Identifiers: NCT00412984 and NCT00262600.", "doi": "10.1161/JAHA.120.018984", "pmid": "33292046", "labels": {"Affinity Proteomics Uppsala": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7955358"}, {"db": "ClinicalTrials.gov", "key": "NCT00412984"}, {"db": "ClinicalTrials.gov", "key": "NCT00262600"}], "notes": [], "created": "2021-12-10T09:28:08.114Z", "modified": "2021-12-10T09:28:08.127Z"}, {"entity": "publication", "iuid": "833bd35c6f9343eca70e9d216f2dac9a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/833bd35c6f9343eca70e9d216f2dac9a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/833bd35c6f9343eca70e9d216f2dac9a"}}, "title": "Rational Design of Azastatin as a Potential ADC Payload with Reduced Bystander Killing.", "authors": [{"family": "Hartmann", "given": "Rafael W", "initials": "RW", "orcid": "0000-0002-5520-0179", "researcher": {"href": "https://publications.scilifelab.se/researcher/7c8d3d38aa874be68232147db4b1dde0.json"}}, {"family": "Fahrner", "given": "Raphael", "initials": "R", "orcid": "0000-0002-6737-0917", "researcher": {"href": "https://publications.scilifelab.se/researcher/4bff9aa2f39b428599d006065f0400d9.json"}}, {"family": "Shevshenko", "given": "Denys", "initials": "D", "orcid": "0000-0001-8779-0153", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe6b3911262c4355af202746e3be90b7.json"}}, {"family": "Fyrkn\u00e4s", "given": "M\u00e5rten", "initials": "M"}, {"family": "Larsson", "given": "Rolf", "initials": "R"}, {"family": "Lehmann", "given": "Fredrik", "initials": "F", "orcid": "0000-0001-7385-3870", "researcher": {"href": "https://publications.scilifelab.se/researcher/822d2043ec8c4d3bb5341a1dfd007d4e.json"}}, {"family": "Odell", "given": "Luke R", "initials": "LR", "orcid": "0000-0001-7658-5103", "researcher": {"href": "https://publications.scilifelab.se/researcher/7653ba79ce9d4e4a80be4b42f516680b.json"}}], "type": "journal article", "published": "2020-12-15", "journal": {"title": "ChemMedChem", "issn": "1860-7187", "volume": "15", "issue": "24", "pages": "2500-2512", "issn-l": "1860-7179"}, "abstract": "Auristatins are a class of ultrapotent microtubule inhibitors, whose growing clinical popularity in oncology is based upon their use as payloads in antibody-drug conjugates (ADCs). The most widely utilized auristatin, MMAE, has however been shown to cause apoptosis in non-pathological cells proximal to the tumour (\"bystander killing\"). Herein, we introduce azastatins, a new class of auristatin derivatives encompassing a side chain amine for antibody conjugation. The synthesis of Cbz-azastatin methyl ester, which included the C2-elongation and diastereoselective reduction of two proteinogenic amino acids as key transformations, was accomplished in 22 steps and 0.76 % overall yield. While Cbz-protected azastatin methyl ester (0.13-3.0 nM) inhibited proliferation more potently than MMAE (0.47-6.5 nM), removal of the Cbz-group yielded dramatically increased IC50 -values (9.8-170 nM). We attribute the reduced apparent cytotoxicity of the deprotected azastatin methyl esters to a lack of membrane permeability. These results clearly establish the azastatins as a novel class of cytotoxic payloads ideally suited for use in next-generation ADC development.", "doi": "10.1002/cmdc.202000497", "pmid": "33063934", "labels": {"Drug Discovery and Development": null}, "xrefs": [{"db": "pmc", "key": "PMC7756782"}], "notes": [], "created": "2021-12-08T12:26:21.225Z", "modified": "2025-10-17T13:05:07.940Z"}, {"entity": "publication", "iuid": "796d298838e14da89a5adb267514aac4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/796d298838e14da89a5adb267514aac4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/796d298838e14da89a5adb267514aac4"}}, "title": "HY5 and phytochrome activity modulate shoot-to-root coordination during thermomorphogenesis in Arabidopsis.", "authors": [{"family": "Gaillochet", "given": "Christophe", "initials": "C"}, {"family": "Burko", "given": "Yogev", "initials": "Y"}, {"family": "Platre", "given": "Matthieu Pierre", "initials": "MP", "orcid": "0000-0002-4934-3050", "researcher": {"href": "https://publications.scilifelab.se/researcher/7fb4dfd55aae43db8a082ca3b2e4d0e0.json"}}, {"family": "Zhang", "given": "Ling", "initials": "L"}, {"family": "Simura", "given": "Jan", "initials": "J"}, {"family": "Willige", "given": "Bj\u00f6rn C", "initials": "BC", "orcid": "0000-0003-4275-5826", "researcher": {"href": "https://publications.scilifelab.se/researcher/92cf9ec5b382449c9c4474b2e5b9e915.json"}}, {"family": "Kumar", "given": "S Vinod", "initials": "SV"}, {"family": "Ljung", "given": "Karin", "initials": "K"}, {"family": "Chory", "given": "Joanne", "initials": "J"}, {"family": "Busch", "given": "Wolfgang", "initials": "W", "orcid": "0000-0003-2042-7290", "researcher": {"href": "https://publications.scilifelab.se/researcher/690f19002a5e49aea937eb9025827fae.json"}}], "type": "journal article", "published": "2020-12-15", "journal": {"title": "Development", "issn": "1477-9129", "volume": "147", "issue": "24", "issn-l": "0950-1991"}, "abstract": "Temperature is one of the most impactful environmental factors to which plants adjust their growth and development. Although the regulation of temperature signaling has been extensively investigated for the aerial part of plants, much less is known and understood about how roots sense and modulate their growth in response to fluctuating temperatures. Here, we found that shoot and root growth responses to high ambient temperature are coordinated during early seedling development in Arabidopsis A shoot signaling module that includes HY5, the phytochromes and the PIFs exerts a central function in coupling these growth responses and maintaining auxin levels in the root. In addition to the HY5/PIF-dependent shoot module, a regulatory axis composed of auxin biosynthesis and auxin perception factors controls root responses to high ambient temperature. Taken together, our findings show that shoot and root developmental responses to temperature are tightly coupled during thermomorphogenesis and suggest that roots integrate energy signals with local hormonal inputs.", "doi": "10.1242/dev.192625", "pmid": "33144393", "labels": {"Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7758624"}, {"db": "pii", "key": "226051"}], "notes": [], "created": "2023-04-12T14:19:44.787Z", "modified": "2025-10-17T13:03:16.496Z"}, {"entity": "publication", "iuid": "2a6a88ecb8924b3cb97256b268e8c722", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2a6a88ecb8924b3cb97256b268e8c722.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2a6a88ecb8924b3cb97256b268e8c722"}}, "title": "Direct energy transfer from photosystem II to photosystem I confers winter sustainability in Scots Pine.", "authors": [{"family": "Bag", "given": "Pushan", "initials": "P", "orcid": "0000-0003-3858-4606", "researcher": {"href": "https://publications.scilifelab.se/researcher/033b97dc712047a294d3e801ba750787.json"}}, {"family": "Chukhutsina", "given": "Volha", "initials": "V"}, {"family": "Zhang", "given": "Zishan", "initials": "Z"}, {"family": "Paul", "given": "Suman", "initials": "S"}, {"family": "Ivanov", "given": "Alexander G", "initials": "AG", "orcid": "0000-0001-7910-5494", "researcher": {"href": "https://publications.scilifelab.se/researcher/1cc5e19a40374d67a3ae74182c5dae6f.json"}}, {"family": "Shutova", "given": "Tatyana", "initials": "T", "orcid": "0000-0002-4095-9609", "researcher": {"href": "https://publications.scilifelab.se/researcher/ec5a10e3ad274526b819f24961ab015e.json"}}, {"family": "Croce", "given": "Roberta", "initials": "R", "orcid": "0000-0003-3469-834X", "researcher": {"href": "https://publications.scilifelab.se/researcher/119277ddfe3b4e9ab4e9afc972f5e763.json"}}, {"family": "Holzwarth", "given": "Alfred R", "initials": "AR", "orcid": "0000-0002-9562-4873", "researcher": {"href": "https://publications.scilifelab.se/researcher/40ce08a698124e0f888d3db0a0644162.json"}}, {"family": "Jansson", "given": "Stefan", "initials": "S", "orcid": "0000-0002-7906-6891", "researcher": {"href": "https://publications.scilifelab.se/researcher/fb9d3c17f4514903b3731d15c622a53d.json"}}], "type": "journal article", "published": "2020-12-15", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "11", "issue": "1", "pages": "6388"}, "abstract": "Evergreen conifers in boreal forests can survive extremely cold (freezing) temperatures during long dark winter and fully recover during summer. A phenomenon called \"sustained quenching\" putatively provides photoprotection and enables their survival, but its precise molecular and physiological mechanisms are not understood. To unveil them, here we have analyzed seasonal adjustment of the photosynthetic machinery of Scots pine (Pinus sylvestris) trees by monitoring multi-year changes in weather, chlorophyll fluorescence, chloroplast ultrastructure, and changes in pigment-protein composition. Analysis of Photosystem II and Photosystem I performance parameters indicate that highly dynamic structural and functional seasonal rearrangements of the photosynthetic apparatus occur. Although several mechanisms might contribute to 'sustained quenching' of winter/early spring pine needles, time-resolved fluorescence analysis shows that extreme down-regulation of photosystem II activity along with direct energy transfer from photosystem II to photosystem I play a major role. This mechanism is enabled by extensive thylakoid destacking allowing for the mixing of PSII with PSI complexes. These two linked phenomena play crucial roles in winter acclimation and protection.", "doi": "10.1038/s41467-020-20137-9", "pmid": "33319777", "labels": {"Integrated Microscopy Technologies Ume\u00e5": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7738668"}, {"db": "pii", "key": "10.1038/s41467-020-20137-9"}], "notes": [], "created": "2022-04-01T15:00:18.942Z", "modified": "2023-06-19T12:41:41.017Z"}, {"entity": "publication", "iuid": "f44fcf7d5d8c4115b4eba8d5c8fbd3f1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f44fcf7d5d8c4115b4eba8d5c8fbd3f1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f44fcf7d5d8c4115b4eba8d5c8fbd3f1"}}, "title": "Cryo-EM structure of native human uromodulin, a zona pellucida module polymer.", "authors": [{"family": "Stsiapanava", "given": "Alena", "initials": "A", "orcid": "0000-0001-6560-011X", "researcher": {"href": "https://publications.scilifelab.se/researcher/7dd9089728fe4d41ab4b6db272e3ed76.json"}}, {"family": "Xu", "given": "Chenrui", "initials": "C", "orcid": "0000-0002-5605-728X", "researcher": {"href": "https://publications.scilifelab.se/researcher/619340ff51bb4d2f8025398a3e3c8135.json"}}, {"family": "Brunati", "given": "Martina", "initials": "M", "orcid": "0000-0002-1010-0836", "researcher": {"href": "https://publications.scilifelab.se/researcher/da793018cb7b4d89915361d08944fe10.json"}}, {"family": "Zamora-Caballero", "given": "Sara", "initials": "S", "orcid": "0000-0003-4717-8845", "researcher": {"href": "https://publications.scilifelab.se/researcher/c561b8843e9f41de9c409f7a681c8663.json"}}, {"family": "Schaeffer", "given": "C\u00e9line", "initials": "C", "orcid": "0000-0001-5883-3951", "researcher": {"href": "https://publications.scilifelab.se/researcher/42307cb5448843d6ab2c6f449da28c57.json"}}, {"family": "Bokhove", "given": "Marcel", "initials": "M", "orcid": "0000-0001-7241-5967", "researcher": {"href": "https://publications.scilifelab.se/researcher/f695b97f38d24caabea3d3c3d59f0890.json"}}, {"family": "Han", "given": "Ling", "initials": "L", "orcid": "0000-0001-9310-4789", "researcher": {"href": "https://publications.scilifelab.se/researcher/1f38b9eaca93474280189bb93b118817.json"}}, {"family": "Hebert", "given": "Hans", "initials": "H", "orcid": "0000-0002-3220-9402", "researcher": {"href": "https://publications.scilifelab.se/researcher/6868ee027bb14470b2d10c762d9b751b.json"}}, {"family": "Carroni", "given": "Marta", "initials": "M", "orcid": "0000-0002-7697-6427", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7f1bc1767024368abcb11a83184994a.json"}}, {"family": "Yasumasu", "given": "Shigeki", "initials": "S", "orcid": "0000-0003-4295-477X", "researcher": {"href": "https://publications.scilifelab.se/researcher/b1a2c2d36d89419da0e3242bf2c85327.json"}}, {"family": "Rampoldi", "given": "Luca", "initials": "L", "orcid": "0000-0002-0544-7042", "researcher": {"href": "https://publications.scilifelab.se/researcher/e09ff90439784c1f81cf41b93e9fcede.json"}}, {"family": "Wu", "given": "Bin", "initials": "B", "orcid": "0000-0002-0883-8006", "researcher": {"href": "https://publications.scilifelab.se/researcher/76dd84c8134245d48bf28f63511fa1ba.json"}}, {"family": "Jovine", "given": "Luca", "initials": "L", "orcid": "0000-0002-2679-6946", "researcher": {"href": "https://publications.scilifelab.se/researcher/8507a7657f6b434ebc572453aa172b1e.json"}}], "type": "journal article", "published": "2020-12-15", "journal": {"title": "EMBO J.", "issn": "1460-2075", "volume": "39", "issue": "24", "pages": "e106807", "issn-l": "0261-4189"}, "abstract": "Assembly of extracellular filaments and matrices mediating fundamental biological processes such as morphogenesis, hearing, fertilization, and antibacterial defense is driven by a ubiquitous polymerization module known as zona pellucida (ZP) \"domain\". Despite the conservation of this element from hydra to humans, no detailed information is available on the filamentous conformation of any ZP module protein. Here, we report a cryo-electron microscopy study of uromodulin (UMOD)/Tamm-Horsfall protein, the most abundant protein in human urine and an archetypal ZP module-containing molecule, in its mature homopolymeric state. UMOD forms a one-start helix with an unprecedented 180-degree twist between subunits enfolded by interdomain linkers that have completely reorganized as a result of propeptide dissociation. Lateral interaction between filaments in the urine generates sheets exposing a checkerboard of binding sites to capture uropathogenic bacteria, and UMOD-based models of heteromeric vertebrate egg coat filaments identify a common sperm-binding region at the interface between subunits.", "doi": "10.15252/embj.2020106807", "pmid": "33196145", "labels": {"Cryo-EM": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC7737619"}, {"db": "PDB", "key": "6TQK"}, {"db": "PDB", "key": "6TQL"}], "notes": [], "created": "2020-11-17T10:27:09.459Z", "modified": "2021-11-10T12:45:16.114Z"}, {"entity": "publication", "iuid": "2d359ec6a7b244e8b37bcc38e6b84edc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2d359ec6a7b244e8b37bcc38e6b84edc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2d359ec6a7b244e8b37bcc38e6b84edc"}}, "title": "Innate lymphoid cell composition associates with COVID-19 disease severity.", "authors": [{"family": "Garc\u00eda", "given": "Marina", "initials": "M", "orcid": "0000-0002-9130-3933", "researcher": {"href": "https://publications.scilifelab.se/researcher/20fa6d5f40764b32a70f792f29d97e60.json"}}, {"family": "Kokkinou", "given": "Efthymia", "initials": "E", "orcid": "0000-0001-9248-4740", "researcher": {"href": "https://publications.scilifelab.se/researcher/d6b45f75457547bfa5326c42ce73e371.json"}}, {"family": "Carrasco Garc\u00eda", "given": "Anna", "initials": "A"}, {"family": "Parrot", "given": "Tiphaine", "initials": "T"}, {"family": "Palma Medina", "given": "Laura M", "initials": "LM"}, {"family": "Maleki", "given": "Kimia T", "initials": "KT"}, {"family": "Christ", "given": "Wanda", "initials": "W"}, {"family": "Varnait\u0117", "given": "Renata", "initials": "R"}, {"family": "Filipovic", "given": "Iva", "initials": "I"}, {"family": "Ljunggren", "given": "Hans-Gustaf", "initials": "HG"}, {"family": "Bj\u00f6rkstr\u00f6m", "given": "Niklas K", "initials": "NK"}, {"family": "Folkesson", "given": "Elin", "initials": "E"}, {"family": "Rooyackers", "given": "Olav", "initials": "O"}, {"family": "Eriksson", "given": "Lars I", "initials": "LI"}, {"family": "S\u00f6nnerborg", "given": "Anders", "initials": "A"}, {"family": "Aleman", "given": "Soo", "initials": "S"}, {"family": "Str\u00e5lin", "given": "Kristoffer", "initials": "K"}, {"family": "Gredmark-Russ", "given": "Sara", "initials": "S"}, {"family": "Klingstr\u00f6m", "given": "Jonas", "initials": "J", "orcid": "0000-0001-9076-1441", "researcher": {"href": "https://publications.scilifelab.se/researcher/95c1b345ae434fb383b7fe6a1d053c80.json"}}, {"family": "Mj\u00f6sberg", "given": "Jenny", "initials": "J", "orcid": "0000-0002-1119-0976", "researcher": {"href": "https://publications.scilifelab.se/researcher/fcca878a7f314944bf1a4290cfd5d71d.json"}}, {"family": "Karolinska KI/K COVID\u201019 Study Group", "given": "", "initials": ""}], "type": "journal article", "published": "2020-12-14", "journal": {"title": "Clin Transl Immunology", "issn": "2050-0068", "volume": "9", "issue": "12", "pages": "e1224", "issn-l": null}, "abstract": "The role of innate lymphoid cells (ILCs) in coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is unknown. Understanding the immune response in COVID-19 could contribute to unravel the pathogenesis and identification of treatment targets. Here, we describe the phenotypic landscape of circulating ILCs in COVID-19 patients and identified ILC phenotypes correlated to serum biomarkers, clinical markers and laboratory parameters relevant in COVID-19.\n\nBlood samples collected from moderately (n = 11) and severely ill (n = 12) COVID-19 patients, as well as healthy control donors (n = 16), were analysed with 18-parameter flow cytometry. Using supervised and unsupervised approaches, we examined the ILC activation status and homing profile. Clinical and laboratory parameters were obtained from all COVID-19 patients, and serum biomarkers were analysed with multiplex immunoassays.\n\nInnate lymphoid cells were largely depleted from the circulation of COVID-19 patients compared with healthy controls. Remaining circulating ILCs revealed decreased frequencies of ILC2 in severe COVID-19, with a concomitant decrease of ILC precursors (ILCp) in all patients, compared with controls. ILC2 and ILCp showed an activated phenotype with increased CD69 expression, whereas expression levels of the chemokine receptors CXCR3 and CCR4 were significantly altered in ILC2 and ILCp, and ILC1, respectively. The activated ILC profile of COVID-19 patients was associated with soluble inflammatory markers, while frequencies of ILC subsets were correlated with laboratory parameters that reflect the disease severity.\n\nThis study provides insights into the potential role of ILCs in immune responses against SARS-CoV-2, particularly linked to the severity of COVID-19.", "doi": "10.1002/cti2.1224", "pmid": "33343897", "labels": {"Affinity Proteomics Stockholm": "Service"}, "xrefs": [{"db": "pii", "key": "CTI21224"}, {"db": "pmc", "key": "PMC7734472"}], "notes": [], "created": "2021-10-06T11:02:11.414Z", "modified": "2022-11-17T18:24:00.884Z"}, {"entity": "publication", "iuid": "da3db1a72f4e4da0b4f59eb56f60145a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/da3db1a72f4e4da0b4f59eb56f60145a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/da3db1a72f4e4da0b4f59eb56f60145a"}}, "title": "Novel Broad-Spectrum Antiviral Inhibitors Targeting Host Factors Essential for Replication of Pathogenic RNA Viruses.", "authors": [{"family": "Tampere", "given": "Marianna", "initials": "M", "orcid": "0000-0001-5744-3206", "researcher": {"href": "https://publications.scilifelab.se/researcher/0c6c86cb20394d17abebb40db23407c8.json"}}, {"family": "Pettke", "given": "Aleksandra", "initials": "A", "orcid": "0000-0001-9375-7755", "researcher": {"href": "https://publications.scilifelab.se/researcher/350bf45edaf64ce1a54b5bb9c27883b5.json"}}, {"family": "Salata", "given": "Cristiano", "initials": "C", "orcid": "0000-0002-5136-7406", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f9a987cf801433ea29960dc97e7fc4d.json"}}, {"family": "Wallner", "given": "Olov", "initials": "O", "orcid": "0000-0002-6481-237X", "researcher": {"href": "https://publications.scilifelab.se/researcher/83eb2f7ee2f34f2cbacaae2dadcd90e9.json"}}, {"family": "Koolmeister", "given": "Tobias", "initials": "T"}, {"family": "Cazares-K\u00f6rner", "given": "Armando", "initials": "A"}, {"family": "Visnes", "given": "Torkild", "initials": "T"}, {"family": "Hesselman", "given": "Maria Carmen", "initials": "MC", "orcid": "0000-0003-4858-6920", "researcher": {"href": "https://publications.scilifelab.se/researcher/c71bbdf11342400ca9031f17a8adca47.json"}}, {"family": "Kunold", "given": "Elena", "initials": "E"}, {"family": "Wiita", "given": "Elisee", "initials": "E"}, {"family": "Kalder\u00e9n", "given": "Christina", "initials": "C"}, {"family": "Lightowler", "given": "Molly", "initials": "M"}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Rosenquist", "given": "\u00c5sa", "initials": "\u00c5"}, {"family": "Warpman-Berglund", "given": "Ulrika", "initials": "U"}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}, {"family": "Mirazimi", "given": "Ali", "initials": "A"}, {"family": "Jafari", "given": "Rozbeh", "initials": "R", "orcid": "0000-0002-3396-4709", "researcher": {"href": "https://publications.scilifelab.se/researcher/481b2a2329634f9086cf52fb808edea5.json"}}, {"family": "Puumalainen", "given": "Marjo-Riitta", "initials": "MR", "orcid": "0000-0002-9936-9734", "researcher": {"href": "https://publications.scilifelab.se/researcher/ffeffbd97cbb4feb9f85e26b368d9f05.json"}}], "type": "journal article", "published": "2020-12-10", "journal": {"title": "Viruses", "issn": "1999-4915", "volume": "12", "issue": "12", "pages": "1423", "issn-l": "1999-4915"}, "abstract": "Recent RNA virus outbreaks such as Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Ebola virus (EBOV) have caused worldwide health emergencies highlighting the urgent need for new antiviral strategies. Targeting host cell pathways supporting viral replication is an attractive approach for development of antiviral compounds, especially with new, unexplored viruses where knowledge of virus biology is limited. Here, we present a strategy to identify host-targeted small molecule inhibitors using an image-based phenotypic antiviral screening assay followed by extensive target identification efforts revealing altered cellular pathways upon antiviral compound treatment. The newly discovered antiviral compounds showed broad-range antiviral activity against pathogenic RNA viruses such as SARS-CoV-2, EBOV and Crimean-Congo hemorrhagic fever virus (CCHFV). Target identification of the antiviral compounds by thermal protein profiling revealed major effects on proteostasis pathways and disturbance in interactions between cellular HSP70 complex and viral proteins, illustrating the supportive role of HSP70 on many RNA viruses across virus families. Collectively, this strategy identifies new small molecule inhibitors with broad antiviral activity against pathogenic RNA viruses, but also uncovers novel virus biology urgently needed for design of new antiviral therapies.", "doi": "10.3390/v12121423", "pmid": "33322045", "labels": {"Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pii", "key": "v12121423"}, {"db": "pmc", "key": "PMC7762994"}], "notes": [], "created": "2021-01-12T18:16:58.814Z", "modified": "2022-03-29T11:28:16.687Z"}, {"entity": "publication", "iuid": "e8bf0479495541e6894495b69ec290b8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e8bf0479495541e6894495b69ec290b8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e8bf0479495541e6894495b69ec290b8"}}, "title": "Hodgkin Lymphoma Monozygotic Triplets Reveal Divergences in DNA Methylation Signatures.", "authors": [{"family": "Xia", "given": "Chuanyou", "initials": "C"}, {"family": "Olsen", "given": "Thale Kristin", "initials": "TK"}, {"family": "Zirakzadeh", "given": "A Ali", "initials": "AA"}, {"family": "Almamoun", "given": "Radwa", "initials": "R"}, {"family": "Sj\u00f6holm", "given": "Louise K", "initials": "LK"}, {"family": "Dahlstr\u00f6m", "given": "Jenny", "initials": "J"}, {"family": "Sj\u00f6berg", "given": "Jan", "initials": "J"}, {"family": "Claesson", "given": "Hans-Erik", "initials": "H"}, {"family": "Johnsen", "given": "John Inge", "initials": "JI"}, {"family": "Winqvist", "given": "Ola", "initials": "O"}, {"family": "Xu", "given": "Dawei", "initials": "D"}, {"family": "Ekstr\u00f6m", "given": "Tomas J", "initials": "TJ"}, {"family": "Bj\u00f6rkholm", "given": "Magnus", "initials": "M"}, {"family": "Str\u00e5\u00e5t", "given": "Klas", "initials": "K"}], "type": "journal article", "published": "2020-12-09", "journal": {"title": "Front Oncol", "issn": "2234-943X", "issn-l": "2234-943X", "volume": "10", "issue": null, "pages": "598872"}, "abstract": "We studied DNA methylation profiles in four different cell populations from a unique constellation of monozygotic triplets in whom two had developed Hodgkin Lymphoma (HL). We detected shared differences in DNA methylation signatures when comparing the two HL-affected triplets with the non-affected triplet. The differences were observed in na\u00efve B-cells and marginal zone-like B-cells. DNA methylation differences were also detected when comparing each of the HL-affected triplets against each other. Even though we cannot determine whether treatment and/or disease triggered the observed differences, we believe our data are important on behalf of forthcoming studies, and that it might provide important clues for a better understanding of HL pathogenesis.", "doi": "10.3389/fonc.2020.598872", "pmid": "33363029", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7756121"}], "notes": [], "created": "2021-01-07T17:01:53.849Z", "modified": "2024-01-16T13:48:41.153Z"}, {"entity": "publication", "iuid": "2d03d3eccf51447f8598cb76587b9f98", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2d03d3eccf51447f8598cb76587b9f98.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2d03d3eccf51447f8598cb76587b9f98"}}, "title": "Capillary leakage provides nutrients and antioxidants for rapid pneumococcal proliferation in influenza-infected lower airways.", "authors": [{"family": "Sender", "given": "Vicky", "initials": "V", "orcid": "0000-0003-2174-946X", "researcher": {"href": "https://publications.scilifelab.se/researcher/806e259d26014318a915ebe132bafb5d.json"}}, {"family": "Hentrich", "given": "Karina", "initials": "K", "orcid": "0000-0001-6660-7233", "researcher": {"href": "https://publications.scilifelab.se/researcher/8dfc3f0078864e68baf26086869ab2d5.json"}}, {"family": "Pathak", "given": "Anuj", "initials": "A"}, {"family": "Tan Qian Ler", "given": "Alicia", "initials": "A", "orcid": "0000-0001-9298-4008", "researcher": {"href": "https://publications.scilifelab.se/researcher/ba872b0c12754f6bb57015ede1d10755.json"}}, {"family": "Embaie", "given": "Bethel Tesfai", "initials": "BT", "orcid": "0000-0002-7081-5032", "researcher": {"href": "https://publications.scilifelab.se/researcher/bc274efbd34147e3972c85858d252a37.json"}}, {"family": "Lundstr\u00f6m", "given": "Susanna L", "initials": "SL"}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "Bergstrand", "given": "Jan", "initials": "J"}, {"family": "Nakamoto", "given": "Rei", "initials": "R", "orcid": "0000-0001-7807-6548", "researcher": {"href": "https://publications.scilifelab.se/researcher/07fdc7bfbb58498d986542fd1ea2cdce.json"}}, {"family": "Sham", "given": "Lok-To", "initials": "L"}, {"family": "Widengren", "given": "Jerker", "initials": "J"}, {"family": "Normark", "given": "Staffan", "initials": "S", "orcid": "0000-0001-7917-3921", "researcher": {"href": "https://publications.scilifelab.se/researcher/72caf78541474b5bbbc2049facb70954.json"}}, {"family": "Henriques-Normark", "given": "Birgitta", "initials": "B"}], "type": "journal article", "published": "2020-12-08", "journal": {"title": "Proc. Natl. Acad. Sci. U.S.A.", "issn": "1091-6490", "issn-l": "0027-8424", "volume": "117", "issue": "49", "pages": "31386-31397"}, "abstract": "Influenza A virus (IAV)-related mortality is often due to secondary bacterial infections, primarily by pneumococci. Here, we study how IAV-modulated changes in the lungs affect bacterial replication in the lower respiratory tract (LRT). Bronchoalveolar lavages (BALs) from coinfected mice showed rapid bacterial proliferation 4 to 6 h after pneumococcal challenge. Metabolomic and quantitative proteomic analyses demonstrated capillary leakage with efflux of nutrients and antioxidants into the alveolar space. Pneumococcal adaptation to IAV-induced inflammation and redox imbalance increased the expression of the pneumococcal chaperone/protease HtrA. Presence of HtrA resulted in bacterial growth advantage in the IAV-infected LRT and protection from complement-mediated opsonophagocytosis due to capsular production. Absence of HtrA led to growth arrest in vitro that was partially restored by antioxidants. Pneumococcal ability to grow in the IAV-infected LRT depends on the nutrient-rich milieu with increased levels of antioxidants such as ascorbic acid and its ability to adapt to and cope with oxidative damage and immune clearance.", "doi": "10.1073/pnas.2012265117", "pmid": "33229573", "labels": {"Chemical Proteomics": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "2012265117"}, {"db": "pmc", "key": "PMC7733805"}], "notes": [], "created": "2020-11-30T11:01:05.695Z", "modified": "2024-01-18T23:34:47.832Z"}, {"entity": "publication", "iuid": "252b7f8a80bd4a9bbd65b8df674d1aed", "links": {"self": {"href": "https://publications.scilifelab.se/publication/252b7f8a80bd4a9bbd65b8df674d1aed.json"}, "display": {"href": "https://publications.scilifelab.se/publication/252b7f8a80bd4a9bbd65b8df674d1aed"}}, "title": "Reaction Wood Anatomical Traits and Hormonal Profiles in Poplar Bent Stem and Root.", "authors": [{"family": "De Zio", "given": "Elena", "initials": "E"}, {"family": "Montagnoli", "given": "Antonio", "initials": "A"}, {"family": "Karady", "given": "Michal", "initials": "M"}, {"family": "Terzaghi", "given": "Mattia", "initials": "M"}, {"family": "Sferra", "given": "Gabriella", "initials": "G"}, {"family": "Antoniadi", "given": "Ioanna", "initials": "I"}, {"family": "Scippa", "given": "Gabriella S", "initials": "GS"}, {"family": "Ljung", "given": "Karin", "initials": "K"}, {"family": "Chiatante", "given": "Donato", "initials": "D"}, {"family": "Trupiano", "given": "Dalila", "initials": "D"}], "type": "journal article", "published": "2020-12-07", "journal": {"title": "Front Plant Sci", "issn": "1664-462X", "volume": "11", "issue": null, "pages": "590985", "issn-l": "1664-462X"}, "abstract": "Reaction wood (RW) formation is an innate physiological response of woody plants to counteract mechanical constraints in nature, reinforce structure and redirect growth toward the vertical direction. Differences and/or similarities between stem and root response to mechanical constraints remain almost unknown especially in relation to phytohormones distribution and RW characteristics. Thus, Populus nigra stem and root subjected to static non-destructive mid-term bending treatment were analyzed. The distribution of tension and compression forces was firstly modeled along the main bent stem and root axis; then, anatomical features, chemical composition, and a complete auxin and cytokinin metabolite profiles of the stretched convex and compressed concave side of three different bent stem and root sectors were analyzed. The results showed that in bent stems RW was produced on the upper stretched convex side whereas in bent roots it was produced on the lower compressed concave side. Anatomical features and chemical analysis showed that bent stem RW was characterized by a low number of vessel, poor lignification, and high carbohydrate, and thus gelatinous layer in fiber cell wall. Conversely, in bent root, RW was characterized by high vessel number and area, without any significant variation in carbohydrate and lignin content. An antagonistic interaction of auxins and different cytokinin forms/conjugates seems to regulate critical aspects of RW formation/development in stem and root to facilitate upward/downward organ bending. The observed differences between the response stem and root to bending highlight how hormonal signaling is highly organ-dependent.", "doi": "10.3389/fpls.2020.590985", "pmid": "33363556", "labels": {"Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7754185"}], "notes": [], "created": "2021-01-12T12:46:48.308Z", "modified": "2025-10-17T13:03:16.508Z"}, {"entity": "publication", "iuid": "a5d51dc3032f481e9020d1483b809ab8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a5d51dc3032f481e9020d1483b809ab8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a5d51dc3032f481e9020d1483b809ab8"}}, "title": "BMP signaling is a therapeutic target in ovarian cancer.", "authors": [{"family": "Fukuda", "given": "Tomohiko", "initials": "T"}, {"family": "Fukuda", "given": "Risa", "initials": "R"}, {"family": "Tanabe", "given": "Ryo", "initials": "R"}, {"family": "Koinuma", "given": "Daizo", "initials": "D"}, {"family": "Koyama", "given": "Hiroo", "initials": "H"}, {"family": "Hashizume", "given": "Yoshinobu", "initials": "Y"}, {"family": "Moustakas", "given": "Aristidis", "initials": "A", "orcid": "0000-0001-9131-3827", "researcher": {"href": "https://publications.scilifelab.se/researcher/6c1626d991f3485e81232db174537e6d.json"}}, {"family": "Miyazono", "given": "Kohei", "initials": "K"}, {"family": "Heldin", "given": "Carl-Henrik", "initials": "CH", "orcid": "0000-0002-9508-896X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f705f7c509904a1db721ace2267ca48f.json"}}], "type": "journal article", "published": "2020-12-05", "journal": {"title": "Cell Death Discov", "issn": "2058-7716", "issn-l": "2058-7716", "volume": "6", "issue": "1", "pages": "139"}, "abstract": "BMP signaling has been found to have tumor-promoting as well as tumor-suppressing effects in different types of tumors. In this study, we investigated the effects of BMP signaling and of BMP inhibitors on ovarian cancer (OC) cells in vitro and in vivo. High expression of BMP receptor 2 (BMPR2) correlated with poor overall survival of OC patients in the TCGA dataset. Both BMP2 and BMPR2 enhanced OC cell proliferation, whereas BMP receptor kinase inhibitors inhibited OC cell growth in cell culture as well as in a mouse model. BMP2 also augmented sphere formation, migration, and invasion of OC cells, and induced EMT. High BMP2 expression was observed after chemotherapy of OC patients in the GSE109934 dataset. In accordance, carboplatin, used for the treatment of OC patients, increased BMP2 secretion from OC cells, and induced EMT partially via activation of BMP signaling. Our data suggest that BMP signaling has tumor-promoting effects in OC, and that BMP inhibitors might be useful therapeutic agents for OC patients. Considering that carboplatin treatment augmented BMP2 secretion, the possibility to use a combination of BMP inhibitors and carboplatin in the treatment of OC patients, would be worth exploring.", "doi": "10.1038/s41420-020-00377-w", "pmid": "33298901", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41420-020-00377-w"}, {"db": "pmc", "key": "PMC7719168"}], "notes": [], "created": "2021-01-11T06:31:10.635Z", "modified": "2021-11-10T12:44:15.555Z"}, {"entity": "publication", "iuid": "ed9dfb96ce7b4525960909d2a2186e16", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ed9dfb96ce7b4525960909d2a2186e16.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ed9dfb96ce7b4525960909d2a2186e16"}}, "title": "Resolution enhancement in NMR spectra by deconvolution with compressed sensing reconstruction.", "authors": [{"family": "Kazimierczuk", "given": "Krzysztof", "initials": "K", "orcid": "0000-0001-9585-1737", "researcher": {"href": "https://publications.scilifelab.se/researcher/ad35e5f050384e6c94bc2d06066a1cf6.json"}}, {"family": "Kasprzak", "given": "Pawe\u0142", "initials": "P", "orcid": "0000-0001-7387-4284", "researcher": {"href": "https://publications.scilifelab.se/researcher/aa6e68d3b1d442efb5418ee75f8f54d0.json"}}, {"family": "Georgoulia", "given": "Panagiota S", "initials": "PS", "orcid": "0000-0003-4573-8052", "researcher": {"href": "https://publications.scilifelab.se/researcher/419e2b2c66404881b3e7a51dbd47fcdb.json"}}, {"family": "Mate\u010dko-Burmann", "given": "Irena", "initials": "I", "orcid": "0000-0001-8873-8381", "researcher": {"href": "https://publications.scilifelab.se/researcher/b8f4fca92f6143aea4378e5e081339ca.json"}}, {"family": "Burmann", "given": "Bj\u00f6rn M", "initials": "BM", "orcid": "0000-0002-3135-7964", "researcher": {"href": "https://publications.scilifelab.se/researcher/b7a6d61fc1a64677874973c3247b1eb4.json"}}, {"family": "Isaksson", "given": "Linn\u00e9a", "initials": "L"}, {"family": "Gustavsson", "given": "Emil", "initials": "E", "orcid": "0000-0003-0166-1786", "researcher": {"href": "https://publications.scilifelab.se/researcher/474b967a7726414288142c12b7b9dc3f.json"}}, {"family": "Westenhoff", "given": "Sebastian", "initials": "S", "orcid": "0000-0002-6961-8015", "researcher": {"href": "https://publications.scilifelab.se/researcher/3f1519bb234b43c6a13833b04e6720b8.json"}}, {"family": "Orekhov", "given": "Vladislav Yu", "initials": "VY", "orcid": "0000-0002-7892-6896", "researcher": {"href": "https://publications.scilifelab.se/researcher/77382c412de04fa08ff7c3bc7087b77e.json"}}], "type": "journal article", "published": "2020-12-04", "journal": {"title": "Chem. Commun. (Camb.)", "issn": "1364-548X", "volume": "56", "issue": "93", "pages": "14585-14588", "issn-l": "1359-7345"}, "abstract": "NMR spectroscopy is one of the basic tools for molecular structure elucidation. Unfortunately, the resolution of the spectra is often limited by inter-nuclear couplings. The existing workarounds often alleviate the problem by trading it for another deficiency, such as spectral artefacts or difficult sample preparation and, thus, are rarely used. We suggest an approach using the coupling deconvolution in the framework of compressed sensing (CS) spectra processing that leads to a major increase in resolution, sensitivity, and overall quality of NUS reconstruction. A new mathematical description of the decoupling by deconvolution explains the effects of thermal noise and reveals a relation with the underlying assumption of the CS. The gain in resolution and sensitivity for challenging molecular systems is demonstrated for the key HNCA experiment used for protein backbone assignment applied to two large proteins: intrinsically disordered 441-residue Tau and a 509-residue globular bacteriophytochrome fragment. The approach will be valuable in a multitude of chemistry applications, where NMR experiments are compromised by the homonuclear scalar coupling.", "doi": "10.1039/d0cc06188c", "pmid": "33146166", "labels": {"Swedish NMR Centre": "Collaborative"}, "xrefs": [], "notes": [], "created": "2020-12-11T09:16:11.124Z", "modified": "2025-10-17T13:03:56.405Z"}, {"entity": "publication", "iuid": "0e0f91643ac84e9e82be060080efcbe8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0e0f91643ac84e9e82be060080efcbe8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0e0f91643ac84e9e82be060080efcbe8"}}, "title": "Structure and Characterization of Phosphoglucomutase 5 from Atlantic and Baltic Herring-An Inactive Enzyme with Intact Substrate Binding.", "authors": [{"family": "Gustafsson", "given": "Robert", "initials": "R", "orcid": "0000-0002-4854-5531", "researcher": {"href": "https://publications.scilifelab.se/researcher/16dd7e73adad4f85972d1d546bfa6d2a.json"}}, {"family": "Eckhard", "given": "Ulrich", "initials": "U", "orcid": "0000-0001-5863-4514", "researcher": {"href": "https://publications.scilifelab.se/researcher/78dae054a57d43c89852aac77a2ad6da.json"}}, {"family": "Ye", "given": "Weihua", "initials": "W"}, {"family": "Enbody", "given": "Erik D", "initials": "ED", "orcid": "0000-0003-1349-628X", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a4df51b279746539cae2fa83c37456d.json"}}, {"family": "Pettersson", "given": "Mats", "initials": "M"}, {"family": "Jemth", "given": "Per", "initials": "P"}, {"family": "Andersson", "given": "Leif", "initials": "L", "orcid": "0000-0002-4085-6968", "researcher": {"href": "https://publications.scilifelab.se/researcher/bd3343c12f994b1fabcae23027d3a76d.json"}}, {"family": "Selmer", "given": "Maria", "initials": "M"}], "type": "journal article", "published": "2020-12-03", "journal": {"title": "Biomolecules", "issn": "2218-273X", "volume": "10", "issue": "12", "issn-l": null}, "abstract": "Phosphoglucomutase 5 (PGM5) in humans is known as a structural muscle protein without enzymatic activity, but detailed understanding of its function is lacking. PGM5 belongs to the alpha-D-phosphohexomutase family and is closely related to the enzymatically active metabolic enzyme PGM1. In the Atlantic herring, Clupea harengus, PGM5 is one of the genes strongly associated with ecological adaptation to the brackish Baltic Sea. We here present the first crystal structures of PGM5, from the Atlantic and Baltic herring, differing by a single substitution Ala330Val. The structure of PGM5 is overall highly similar to structures of PGM1. The structure of the Baltic herring PGM5 in complex with the substrate glucose-1-phosphate shows conserved substrate binding and active site compared to human PGM1, but both PGM5 variants lack phosphoglucomutase activity under the tested conditions. Structure comparison and sequence analysis of PGM5 and PGM1 from fish and mammals suggest that the lacking enzymatic activity of PGM5 is related to differences in active-site loops that are important for flipping of the reaction intermediate. The Ala330Val substitution does not alter structure or biophysical properties of PGM5 but, due to its surface-exposed location, could affect interactions with protein-binding partners.", "doi": "10.3390/biom10121631", "pmid": "33287293", "labels": {"Protein Science Facility (PSF)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7761743"}, {"db": "pii", "key": "biom10121631"}], "notes": [], "created": "2024-04-03T14:12:52.445Z", "modified": "2024-04-03T14:12:52.932Z"}, {"entity": "publication", "iuid": "c6ac69c76dae4296b4cfe9afc374fcaf", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c6ac69c76dae4296b4cfe9afc374fcaf.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c6ac69c76dae4296b4cfe9afc374fcaf"}}, "title": "A Model of Germinal Matrix Hemorrhage in Preterm Rat Pups.", "authors": [{"family": "Jinnai", "given": "Masako", "initials": "M"}, {"family": "Koning", "given": "Gabriella", "initials": "G"}, {"family": "Singh-Mallah", "given": "Gagandeep", "initials": "G"}, {"family": "Jonsdotter", "given": "Andrea", "initials": "A"}, {"family": "Leverin", "given": "Anna-Lena", "initials": "AL"}, {"family": "Svedin", "given": "Pernilla", "initials": "P"}, {"family": "Nair", "given": "Syam", "initials": "S"}, {"family": "Takeda", "given": "Satoru", "initials": "S"}, {"family": "Wang", "given": "Xiaoyang", "initials": "X"}, {"family": "Mallard", "given": "Carina", "initials": "C"}, {"family": "Ek", "given": "Carl Joakim", "initials": "CJ"}, {"family": "Rocha-Ferreira", "given": "Eridan", "initials": "E"}, {"family": "Hagberg", "given": "Henrik", "initials": "H"}], "type": "journal article", "published": "2020-12-03", "journal": {"title": "Front Cell Neurosci", "issn": "1662-5102", "volume": "14", "pages": "535320", "issn-l": "1662-5102"}, "abstract": "Germinal matrix hemorrhage (GMH) is a serious complication in extremely preterm infants associated with neurological deficits and mortality. The purpose of the present study was to develop and characterize a grade III and IV GMH model in postnatal day 5 (P5) rats, the equivalent of preterm human brain maturation. P5 Wistar rats were exposed to unilateral GMH through intracranial injection into the striatum close to the germinal matrix with 0.1, 0.2, or 0.3 U of collagenase VII. During 10 days following GMH induction, motor functions and body weight were assessed and brain tissue collected at P16. Animals were tested for anxiety, motor coordination and motor asymmetry on P22-26 and P36-40. Using immunohistochemical staining and neuropathological scoring we found that a collagenase dose of 0.3 U induced GMH. Neuropathological assessment revealed that the brain injury in the collagenase group was characterized by dilation of the ipsilateral ventricle combined with mild to severe cellular necrosis as well as mild to moderate atrophy at the levels of striatum and subcortical white matter, and to a lesser extent, hippocampus and cortex. Within 0.5 h post-collagenase injection there was clear bleeding at the site of injury, with progressive increase in iron and infiltration of neutrophils in the first 24 h, together with focal microglia activation. By P16, blood was no longer observed, although significant gray and white matter brain infarction persisted. Astrogliosis was also detected at this time-point. Animals exposed to GMH performed worse than controls in the negative geotaxis test and also opened their eyes with latency compared to control animals. At P40, GMH rats spent more time in the center of open field box and moved at higher speed compared to the controls, and continued to show ipsilateral injury in striatum and subcortical white matter. We have established a P5 rat model of collagenase-induced GMH for the study of preterm brain injury. Our results show that P5 rat pups exposed to GMH develop moderate brain injury affecting both gray and white matter associated with delayed eye opening and abnormal motor functions. These animals develop hyperactivity and show reduced anxiety in the juvenile stage.", "doi": "10.3389/fncel.2020.535320", "pmid": "33343300", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7744792"}], "notes": [], "created": "2023-02-16T08:07:43.072Z", "modified": "2023-02-16T08:07:43.092Z"}, {"entity": "publication", "iuid": "7c65da05f8c44cc08507b044f77cc22e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7c65da05f8c44cc08507b044f77cc22e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7c65da05f8c44cc08507b044f77cc22e"}}, "title": "Moose genomes reveal past glacial demography and the origin of modern lineages.", "authors": [{"family": "Dussex", "given": "Nicolas", "initials": "N", "orcid": "0000-0002-9179-8593", "researcher": {"href": "https://publications.scilifelab.se/researcher/a8ce91163131424a99f8815c2cb96953.json"}}, {"family": "Alberti", "given": "Federica", "initials": "F"}, {"family": "Heino", "given": "Matti T", "initials": "MT"}, {"family": "Olsen", "given": "Remi-Andre", "initials": "R"}, {"family": "van der Valk", "given": "Tom", "initials": "T"}, {"family": "Ryman", "given": "Nils", "initials": "N"}, {"family": "Laikre", "given": "Linda", "initials": "L"}, {"family": "Ahlgren", "given": "Hans", "initials": "H"}, {"family": "Askeyev", "given": "Igor V", "initials": "IV"}, {"family": "Askeyev", "given": "Oleg V", "initials": "OV"}, {"family": "Shaymuratova", "given": "Dilyara N", "initials": "DN"}, {"family": "Askeyev", "given": "Arthur O", "initials": "AO"}, {"family": "D\u00f6ppes", "given": "Doris", "initials": "D"}, {"family": "Friedrich", "given": "Ronny", "initials": "R"}, {"family": "Lindauer", "given": "Susanne", "initials": "S"}, {"family": "Rosendahl", "given": "Wilfried", "initials": "W"}, {"family": "Aspi", "given": "Jouni", "initials": "J"}, {"family": "Hofreiter", "given": "Michael", "initials": "M"}, {"family": "Lid\u00e9n", "given": "Kerstin", "initials": "K"}, {"family": "Dal\u00e9n", "given": "Love", "initials": "L", "orcid": "0000-0001-8270-7613", "researcher": {"href": "https://publications.scilifelab.se/researcher/48ecf726779249ac9d12f4f7a1cc62bf.json"}}, {"family": "D\u00edez-Del-Molino", "given": "David", "initials": "D"}], "type": "journal article", "published": "2020-12-02", "journal": {"title": "BMC Genomics", "issn": "1471-2164", "issn-l": "1471-2164", "volume": "21", "issue": "1", "pages": "854"}, "abstract": "Numerous megafauna species from northern latitudes went extinct during the Pleistocene/Holocene transition as a result of climate-induced habitat changes. However, several ungulate species managed to successfully track their habitats during this period to eventually flourish and recolonise the holarctic regions. So far, the genomic impacts of these climate fluctuations on ungulates from high latitudes have been little explored. Here, we assemble a de-novo genome for the European moose (Alces alces) and analyse it together with re-sequenced nuclear genomes and ancient and modern mitogenomes from across the moose range in Eurasia and North America.\r\n\r\nWe found that moose demographic history was greatly influenced by glacial cycles, with demographic responses to the Pleistocene/Holocene transition similar to other temperate ungulates. Our results further support that modern moose lineages trace their origin back to populations that inhabited distinct glacial refugia during the Last Glacial Maximum (LGM). Finally, we found that present day moose in Europe and North America show low to moderate inbreeding levels resulting from post-glacial bottlenecks and founder effects, but no evidence for recent inbreeding resulting from human-induced population declines.\r\n\r\nTaken together, our results highlight the dynamic recent evolutionary history of the moose and provide an important resource for further genomic studies.", "doi": "10.1186/s12864-020-07208-3", "pmid": "33267779", "labels": {"NGI Stockholm (Genomics Production)": "Collaborative", "National Genomics Infrastructure": "Collaborative", "NGI Stockholm (Genomics Applications)": "Collaborative", "Bioinformatics Long-term Support WABI": "Service", "Bioinformatics Support, Infrastructure and Training": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12864-020-07208-3"}, {"db": "pmc", "key": "PMC7709250"}], "notes": [], "created": "2020-12-07T16:36:41.615Z", "modified": "2023-09-07T14:58:17.282Z"}, {"entity": "publication", "iuid": "57ca428a48ab4083bac74819a26c8f5f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/57ca428a48ab4083bac74819a26c8f5f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/57ca428a48ab4083bac74819a26c8f5f"}}, "title": "Bromopyrylium Derivatization Facilitates Identification by Mass Spectrometry Imaging of Monoamine Neurotransmitters and Small Molecule Neuroactive Compounds.", "authors": [{"family": "Shariatgorji", "given": "Reza", "initials": "R", "orcid": "0000-0001-9484-0921", "researcher": {"href": "https://publications.scilifelab.se/researcher/7762e9f6779c4780a4077c557eb7a3b6.json"}}, {"family": "Nilsson", "given": "Anna", "initials": "A"}, {"family": "Strittmatter", "given": "Nicole", "initials": "N"}, {"family": "Vallianatou", "given": "Theodosia", "initials": "T"}, {"family": "Zhang", "given": "Xiaoqun", "initials": "X"}, {"family": "Svenningsson", "given": "Per", "initials": "P"}, {"family": "Goodwin", "given": "Richard J A", "initials": "RJA"}, {"family": "Andr\u00e9n", "given": "Per E", "initials": "PE", "orcid": "0000-0002-4062-7743", "researcher": {"href": "https://publications.scilifelab.se/researcher/64f6381de42949db8d30b56b526f3e26.json"}}], "type": "journal article", "published": "2020-12-02", "journal": {"title": "J. Am. Soc. Mass Spectrom.", "issn": "1879-1123", "volume": "31", "issue": "12", "pages": "2553-2557", "issn-l": "1044-0305"}, "abstract": "Mass spectrometry imaging using matrix-assisted laser desorption/ionization and desorption electrospray ionization has recently been employed to investigate the distribution of neurotransmitters, including biogenic amines and amino acids, directly in brain tissue sections. Ionization is facilitated by charge-tagging through pyrylium derivatization of primary amine containing neurotransmitters directly in tissue sections, significantly improving the limit of detection. Since the derivatization adds carbon and hydrogen to the target compounds, the resulting isotopic patterns of the products are not distinctive from those of the nonderivatized species. Here, we describe an approach for chemically modifying the reactive pyrylium ion to introduce the distinct isotopic signature of bromine in mass spectra of chemically derivatized substances in tissue sections. The method enables monoamine compounds to be distinguished directly in tissue sections, facilitating their identification.", "doi": "10.1021/jasms.0c00166", "pmid": "32633532", "labels": {"Spatial Mass Spectrometry": "Technology development"}, "xrefs": [], "notes": [], "created": "2021-03-26T12:44:24.210Z", "modified": "2021-12-03T11:51:42.177Z"}, {"entity": "publication", "iuid": "b35ea53385974fc2b330d4aa37a35fbc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b35ea53385974fc2b330d4aa37a35fbc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b35ea53385974fc2b330d4aa37a35fbc"}}, "title": "A shotgun metagenomic investigation of the microbiota of udder cleft dermatitis in comparison to healthy skin in dairy cows.", "authors": [{"family": "Ekman", "given": "Lisa", "initials": "L", "orcid": "0000-0002-6556-1111", "researcher": {"href": "https://publications.scilifelab.se/researcher/caf7be02284c489a937dd91b1ff7e743.json"}}, {"family": "Bagge", "given": "Elisabeth", "initials": "E"}, {"family": "Nyman", "given": "Ann", "initials": "A", "orcid": "0000-0002-6643-0404", "researcher": {"href": "https://publications.scilifelab.se/researcher/1affe77f7a6a432a8ed538cb0acc1001.json"}}, {"family": "Persson Waller", "given": "Karin", "initials": "K"}, {"family": "Pringle", "given": "M\u00e4rit", "initials": "M"}, {"family": "Segerman", "given": "Bo", "initials": "B"}], "type": "journal article", "published": "2020-12-02", "journal": {"title": "PLoS ONE", "issn": "1932-6203", "volume": "15", "issue": "12", "pages": "e0242880", "issn-l": "1932-6203"}, "abstract": "Udder cleft dermatitis (UCD) is a skin condition affecting the fore udder attachment of dairy cows. UCD may be defined as mild (eczematous skin changes) or severe (open wounds, large skin changes). Our aims were to compare the microbiota of mild and severe UCD lesions with the microbiota of healthy skin from the fore udder attachment of control cows, and to investigate whether mastitis-causing pathogens are present in UCD lesions. Samples were obtained from cows in six dairy herds. In total, 36 UCD samples categorized as mild (n = 17) or severe (n = 19) and 13 control samples were sequenced using a shotgun metagenomic approach and the reads were taxonomically classified based on their k-mer content. The Wilcoxon rank sum test was used to compare the abundance of different taxa between different sample types, as well as to compare the bacterial diversity between samples. A high proportion of bacteria was seen in all samples. Control samples had a higher proportion of archaeal reads, whereas most samples had low proportions of fungi, protozoa and viruses. The bacterial microbiota differed between controls and mild and severe UCD samples in both composition and diversity. Subgroups of UCD samples were visible, characterized by increased proportion of one or a few bacterial genera or species, e.g. Corynebacterium, Staphylococcus, Brevibacterium luteolum, Trueperella pyogenes and Fusobacterium necrophorum. Bifidobacterium spp. were more common in controls compared to UCD samples. The bacterial diversity was higher in controls compared to UCD samples. Bacteria commonly associated with mastitis were uncommon. In conclusion, a dysbiosis of the microbiota of mild and severe UCD samples was seen, characterized by decreased diversity and an increased proportion of certain bacteria. There was no evidence of a specific pathogen causing UCD or that UCD lesions are important reservoirs for mastitis-causing bacteria.", "doi": "10.1371/journal.pone.0242880", "pmid": "33264351", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "PONE-D-20-18567"}, {"db": "pmc", "key": "PMC7710049"}], "notes": [], "created": "2020-12-08T23:31:10.074Z", "modified": "2024-01-16T13:48:41.169Z"}, {"entity": "publication", "iuid": "4508bd9d4cb6483f9bb4e4f390fdd0ef", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4508bd9d4cb6483f9bb4e4f390fdd0ef.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4508bd9d4cb6483f9bb4e4f390fdd0ef"}}, "title": "Whole blood co-expression modules associate with metabolic traits and type 2 diabetes: an IMI-DIRECT study.", "authors": [{"family": "Gudmundsdottir", "given": "Valborg", "initials": "V"}, {"family": "Pedersen", "given": "Helle Krogh", "initials": "HK"}, {"family": "Mazzoni", "given": "Gianluca", "initials": "G"}, {"family": "Allin", "given": "Kristine H", "initials": "KH"}, {"family": "Artati", "given": "Anna", "initials": "A"}, {"family": "Beulens", "given": "Joline W", "initials": "JW"}, {"family": "Banasik", "given": "Karina", "initials": "K"}, {"family": "Brorsson", "given": "Caroline", "initials": "C"}, {"family": "Cederberg", "given": "Henna", "initials": "H"}, {"family": "Chabanova", "given": "Elizaveta", "initials": "E"}, {"family": "De Masi", "given": "Federico", "initials": "F"}, {"family": "Elders", "given": "Petra J", "initials": "PJ"}, {"family": "Forgie", "given": "Ian", "initials": "I"}, {"family": "Giordano", "given": "Giuseppe N", "initials": "GN"}, {"family": "Grallert", "given": "Harald", "initials": "H"}, {"family": "Gupta", "given": "Ramneek", "initials": "R"}, {"family": "Haid", "given": "Mark", "initials": "M"}, {"family": "Hansen", "given": "Torben", "initials": "T"}, {"family": "Hansen", "given": "Tue H", "initials": "TH"}, {"family": "Hattersley", "given": "Andrew T", "initials": "AT"}, {"family": "Heggie", "given": "Alison", "initials": "A"}, {"family": "Hong", "given": "Mun-Gwan", "initials": "MG"}, {"family": "Jones", "given": "Angus G", "initials": "AG"}, {"family": "Koivula", "given": "Robert", "initials": "R"}, {"family": "Kokkola", "given": "Tarja", "initials": "T"}, {"family": "Laakso", "given": "Markku", "initials": "M"}, {"family": "L\u00f8ngreen", "given": "Peter", "initials": "P"}, {"family": "Mahajan", "given": "Anubha", "initials": "A"}, {"family": "Mari", "given": "Andrea", "initials": "A"}, {"family": "McDonald", "given": "Timothy J", "initials": "TJ"}, {"family": "McEvoy", "given": "Donna", "initials": "D"}, {"family": "Musholt", "given": "Petra B", "initials": "PB"}, {"family": "Pavo", "given": "Imre", "initials": "I"}, {"family": "Prehn", "given": "Cornelia", "initials": "C"}, {"family": "Ruetten", "given": "Hartmut", "initials": "H"}, {"family": "Ridderstr\u00e5le", "given": "Martin", "initials": "M"}, {"family": "Rutters", "given": "Femke", "initials": "F"}, {"family": "Sharma", "given": "Sapna", "initials": "S"}, {"family": "Slieker", "given": "Roderick C", "initials": "RC"}, {"family": "Syed", "given": "Ali", "initials": "A"}, {"family": "Tajes", "given": "Juan Fernandez", "initials": "JF"}, {"family": "Thomas", "given": "Cecilia Engel", "initials": "CE"}, {"family": "Thomsen", "given": "Henrik S", "initials": "HS"}, {"family": "Vangipurapu", "given": "Jagadish", "initials": "J"}, {"family": "Vestergaard", "given": "Henrik", "initials": "H"}, {"family": "Vi\u00f1uela", "given": "Ana", "initials": "A"}, {"family": "Wesolowska-Andersen", "given": "Agata", "initials": "A"}, {"family": "Walker", "given": "Mark", "initials": "M"}, {"family": "Adamski", "given": "Jerzy", "initials": "J"}, {"family": "Schwenk", "given": "Jochen M", "initials": "JM", "orcid": "0000-0001-8141-8449", "researcher": {"href": "https://publications.scilifelab.se/researcher/aba5822711b246b397fffacb7ae403b3.json"}}, {"family": "McCarthy", "given": "Mark I", "initials": "MI"}, {"family": "Pearson", "given": "Ewan", "initials": "E"}, {"family": "Dermitzakis", "given": "Emmanouil", "initials": "E"}, {"family": "Franks", "given": "Paul W", "initials": "PW"}, {"family": "Pedersen", "given": "Oluf", "initials": "O"}, {"family": "Brunak", "given": "S\u00f8ren", "initials": "S", "orcid": "0000-0003-0316-5866", "researcher": {"href": "https://publications.scilifelab.se/researcher/76fd1f30268c450092b654e25a5db4ee.json"}}], "type": "journal article", "published": "2020-12-01", "journal": {"title": "Genome Med", "issn": "1756-994X", "issn-l": "1756-994X", "volume": "12", "issue": "1", "pages": "109"}, "abstract": "The rising prevalence of type 2 diabetes (T2D) poses a major global challenge. It remains unresolved to what extent transcriptomic signatures of metabolic dysregulation and T2D can be observed in easily accessible tissues such as blood. Additionally, large-scale human studies are required to further our understanding of the putative inflammatory component of insulin resistance and T2D. Here we used transcriptomics data from individuals with (n = 789) and without (n = 2127) T2D from the IMI-DIRECT cohorts to describe the co-expression structure of whole blood that mainly reflects processes and cell types of the immune system, and how it relates to metabolically relevant clinical traits and T2D.\n\nClusters of co-expressed genes were identified in the non-diabetic IMI-DIRECT cohort and evaluated with regard to stability, as well as preservation and rewiring in the cohort of individuals with T2D. We performed functional and immune cell signature enrichment analyses, and a genome-wide association study to describe the genetic regulation of the modules. Phenotypic and trans-omics associations of the transcriptomic modules were investigated across both IMI-DIRECT cohorts.\n\nWe identified 55 whole blood co-expression modules, some of which clustered in larger super-modules. We identified a large number of associations between these transcriptomic modules and measures of insulin action and glucose tolerance. Some of the metabolically linked modules reflect neutrophil-lymphocyte ratio in blood while others are independent of white blood cell estimates, including a module of genes encoding neutrophil granule proteins with antibacterial properties for which the strongest associations with clinical traits and T2D status were observed. Through the integration of genetic and multi-omics data, we provide a holistic view of the regulation and molecular context of whole blood transcriptomic modules. We furthermore identified an overlap between genetic signals for T2D and co-expression modules involved in type II interferon signaling.\n\nOur results offer a large-scale map of whole blood transcriptomic modules in the context of metabolic disease and point to novel biological candidates for future studies related to T2D.", "doi": "10.1186/s13073-020-00806-6", "pmid": "33261667", "labels": {"Affinity Proteomics Stockholm": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1186/s13073-020-00806-6"}, {"db": "pmc", "key": "PMC7708171"}], "notes": [], "created": "2020-12-10T19:03:50.791Z", "modified": "2021-11-10T12:44:28.124Z"}, {"entity": "publication", "iuid": "c1ad66f306e5476dab917903696bc964", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c1ad66f306e5476dab917903696bc964.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c1ad66f306e5476dab917903696bc964"}}, "title": "Solid-state NMR methods for studying membrane systems", "authors": [{"family": "Gr\u00f6bner", "given": "Gerhard", "initials": "G", "orcid": "0000-0001-7380-8797", "researcher": {"href": "https://publications.scilifelab.se/researcher/85bd86ebc85d4653bc880bc9be25bc80.json"}}, {"family": "Williamson", "given": "Philip", "initials": "P", "orcid": "0000-0002-0231-8640", "researcher": {"href": "https://publications.scilifelab.se/researcher/034a75ccf4884c4ba4b2f9962734d693.json"}}], "type": "book-chapter", "published": "2020-12-01", "journal": {"title": "ISBN: 978-0-7503-2530-1", "issn": "ISBN: 978-0-7503-2530-1", "issn-l": null, "volume": null, "issue": null, "pages": "1-1-1-30"}, "abstract": null, "doi": "10.1088/978-0-7503-2532-5ch1", "pmid": null, "labels": {"Swedish NMR Centre": "Collaborative"}, "xrefs": [], "notes": [], "created": "2020-12-09T15:43:56.786Z", "modified": "2025-12-18T20:05:56.380Z"}, {"entity": "publication", "iuid": "5660b7d3ef2044dca8d30c36ddc899a1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5660b7d3ef2044dca8d30c36ddc899a1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5660b7d3ef2044dca8d30c36ddc899a1"}}, "title": "Amplification-free long-read sequencing reveals unforeseen CRISPR-Cas9 off-target activity.", "authors": [{"family": "H\u00f6ijer", "given": "Ida", "initials": "I", "orcid": "0000-0002-3915-3384", "researcher": {"href": "https://publications.scilifelab.se/researcher/4ba4ce20b1b447ada4fdc8256211436e.json"}}, {"family": "Johansson", "given": "Josefin", "initials": "J"}, {"family": "Gudmundsson", "given": "Sanna", "initials": "S"}, {"family": "Chin", "given": "Chen-Shan", "initials": "CS"}, {"family": "Bunikis", "given": "Ignas", "initials": "I"}, {"family": "H\u00e4ggqvist", "given": "Susana", "initials": "S"}, {"family": "Emmanouilidou", "given": "Anastasia", "initials": "A"}, {"family": "Wilbe", "given": "Maria", "initials": "M"}, {"family": "den Hoed", "given": "Marcel", "initials": "M"}, {"family": "Bondeson", "given": "Marie-Louise", "initials": "ML"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Gyllensten", "given": "Ulf", "initials": "U"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}], "type": "journal article", "published": "2020-12-01", "journal": {"title": "Genome Biol.", "issn": "1474-760X", "volume": "21", "issue": "1", "pages": "290", "issn-l": "1474-7596"}, "abstract": "One ongoing concern about CRISPR-Cas9 genome editing is that unspecific guide RNA (gRNA) binding may induce off-target mutations. However, accurate prediction of CRISPR-Cas9 off-target activity is challenging. Here, we present SMRT-OTS and Nano-OTS, two novel, amplification-free, long-read sequencing protocols for detection of gRNA-driven digestion of genomic DNA by Cas9 in vitro.\n\nThe methods are assessed using the human cell line HEK293, re-sequenced at 18x coverage using highly accurate HiFi SMRT reads. SMRT-OTS and Nano-OTS are first applied to three different gRNAs targeting HEK293 genomic DNA, resulting in a set of 55 high-confidence gRNA cleavage sites identified by both methods. Twenty-five of these sites are not reported by off-target prediction software, either because they contain four or more single nucleotide mismatches or insertion/deletion mismatches, as compared with the human reference. Additional experiments reveal that 85% of Cas9 cleavage sites are also found by other in vitro-based methods and that on- and off-target sites are detectable in gene bodies where short-reads fail to uniquely align. Even though SMRT-OTS and Nano-OTS identify several sites with previously validated off-target editing activity in cells, our own CRISPR-Cas9 editing experiments in human fibroblasts do not give rise to detectable off-target mutations at the in vitro-predicted sites. However, indel and structural variation events are enriched at the on-target sites.\n\nAmplification-free long-read sequencing reveals Cas9 cleavage sites in vitro that would have been difficult to predict using computational tools, including in dark genomic regions inaccessible by short-read sequencing.", "doi": "10.1186/s13059-020-02206-w", "pmid": "33261648", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Technology development", "National Genomics Infrastructure": "Technology development", "Clinical Genomics Uppsala": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1186/s13059-020-02206-w"}, {"db": "pmc", "key": "PMC7706270"}], "notes": [], "created": "2020-12-03T21:44:41.975Z", "modified": "2024-01-16T13:48:41.187Z"}, {"entity": "publication", "iuid": "144f11f34c2647769832d1490ea233c6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/144f11f34c2647769832d1490ea233c6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/144f11f34c2647769832d1490ea233c6"}}, "title": "Tissue-specific patterns of regulatory changes underlying gene expression differences among Ficedula flycatchers and their naturally occurring F1 hybrids.", "authors": [{"family": "Mugal", "given": "Carina F", "initials": "CF", "orcid": "0000-0003-4220-4928", "researcher": {"href": "https://publications.scilifelab.se/researcher/8b82f77594994c37b37c72b653e20c28.json"}}, {"family": "Wang", "given": "Mi", "initials": "M"}, {"family": "Backstr\u00f6m", "given": "Niclas", "initials": "N"}, {"family": "Wheatcroft", "given": "David", "initials": "D"}, {"family": "\u00c5lund", "given": "Murielle", "initials": "M"}, {"family": "S\u00e9mon", "given": "Marie", "initials": "M"}, {"family": "McFarlane", "given": "S Eryn", "initials": "SE"}, {"family": "Dutoit", "given": "Ludovic", "initials": "L"}, {"family": "Qvarnstr\u00f6m", "given": "Anna", "initials": "A"}, {"family": "Ellegren", "given": "Hans", "initials": "H", "orcid": "0000-0002-5035-1736", "researcher": {"href": "https://publications.scilifelab.se/researcher/819e68cc7125446baec6165aabd2d19c.json"}}], "type": "journal article", "published": "2020-12-00", "journal": {"title": "Genome Res.", "issn": "1549-5469", "volume": "30", "issue": "12", "pages": "1727-1739", "issn-l": "1088-9051"}, "abstract": "Changes in interacting cis- and trans-regulatory elements are important candidates for Dobzhansky-Muller hybrid incompatibilities and may contribute to hybrid dysfunction by giving rise to misexpression in hybrids. To gain insight into the molecular mechanisms and determinants of gene expression evolution in natural populations, we analyzed the transcriptome from multiple tissues of two recently diverged Ficedula flycatcher species and their naturally occurring F1 hybrids. Differential gene expression analysis revealed that the extent of differentiation between species and the set of differentially expressed genes varied across tissues. Common to all tissues, a higher proportion of Z-linked genes than autosomal genes showed differential expression, providing evidence for a fast-Z effect. We further found clear signatures of hybrid misexpression in brain, heart, kidney, and liver. However, while testis showed the highest divergence of gene expression among tissues, it showed no clear signature of misexpression in F1 hybrids, even though these hybrids were found to be sterile. It is therefore unlikely that incompatibilities between cis-trans regulatory changes explain the observed sterility. Instead, we found evidence that cis-regulatory changes play a significant role in the evolution of gene expression in testis, which illustrates the tissue-specific nature of cis-regulatory evolution bypassing constraints associated with pleiotropic effects of genes.", "doi": "10.1101/gr.254508.119", "pmid": "33144405", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "gr.254508.119"}, {"db": "pmc", "key": "PMC7706733"}], "notes": [], "created": "2020-12-08T23:45:03.587Z", "modified": "2024-01-16T13:48:41.199Z"}, {"entity": "publication", "iuid": "d787ebed6379499b968ca423e460aa66", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d787ebed6379499b968ca423e460aa66.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d787ebed6379499b968ca423e460aa66"}}, "title": "The methylation landscape and its role in domestication and gene regulation in the chicken.", "authors": [{"family": "H\u00f6glund", "given": "Andrey", "initials": "A"}, {"family": "Henriksen", "given": "Rie", "initials": "R"}, {"family": "Fogelholm", "given": "Jesper", "initials": "J"}, {"family": "Churcher", "given": "Allison M", "initials": "AM", "orcid": "0000-0003-1902-3002", "researcher": {"href": "https://publications.scilifelab.se/researcher/d97e6fb500a043f08d4f882e802cd91b.json"}}, {"family": "Guerrero-Bosagna", "given": "Carlos M", "initials": "CM", "orcid": "0000-0003-1935-5875", "researcher": {"href": "https://publications.scilifelab.se/researcher/0175a0da7ca147d4a0430b085ed23669.json"}}, {"family": "Martinez-Barrio", "given": "Alvaro", "initials": "A", "orcid": "0000-0001-5064-2093", "researcher": {"href": "https://publications.scilifelab.se/researcher/d6ff319fe64340f2bb2350121848ecff.json"}}, {"family": "Johnsson", "given": "Martin", "initials": "M"}, {"family": "Jensen", "given": "Per", "initials": "P"}, {"family": "Wright", "given": "Dominic", "initials": "D", "orcid": "0000-0003-2329-2635", "researcher": {"href": "https://publications.scilifelab.se/researcher/6447b896ea3b453ab10136b5f44ae241.json"}}], "type": "journal article", "published": "2020-12-00", "journal": {"title": "Nat Ecol Evol", "issn": "2397-334X", "volume": "4", "issue": "12", "pages": "1713-1724", "issn-l": "2397-334X"}, "abstract": "Domestication is one of the strongest examples of artificial selection and has produced some of the most extreme within-species phenotypic variation known. In the case of the chicken, it has been hypothesized that DNA methylation may play a mechanistic role in the domestication response. By inter-crossing wild-derived red junglefowl with domestic chickens, we mapped quantitative trait loci for hypothalamic methylation (methQTL), gene expression (eQTL) and behaviour. We find large, stable methylation differences, with 6,179 cis and 2,973 trans methQTL identified. Over 46% of the trans effects were genotypically controlled by five loci, mainly associated with increased methylation in the junglefowl genotype. In a third of eQTL, we find that there is a correlation between gene expression and methylation, while statistical causality analysis reveals multiple instances where methylation is driving gene expression, as well as the reverse. We also show that methylation is correlated with some aspects of behavioural variation in the inter-cross. In conclusion, our data suggest a role for methylation in the regulation of gene expression underlying the domesticated phenotype of the chicken.", "doi": "10.1038/s41559-020-01310-1", "pmid": "32958860", "labels": {"Bioinformatics Long-term Support WABI": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41559-020-01310-1"}, {"db": "figshare", "key": "10.6084/m9.figshare.12803873"}, {"db": "figshare", "key": "10.6084/m9.figshare.12803876"}, {"db": "figshare", "key": "10.6084/m9.figshare.12803870"}], "notes": [], "created": "2020-09-25T11:36:26.073Z", "modified": "2024-01-16T13:48:41.219Z"}, {"entity": "publication", "iuid": "bba8d3b0e39d4c35b16e5b9a701a5718", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bba8d3b0e39d4c35b16e5b9a701a5718.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bba8d3b0e39d4c35b16e5b9a701a5718"}}, "title": "Surface analysis of bacterial systems using cryo\u2010X\u2010ray photoelectron spectroscopy", "authors": [{"family": "Hagberg", "given": "Aleksandra", "initials": "A"}, {"family": "Rzhepishevska", "given": "Olena", "initials": "O", "orcid": "0000-0002-7912-7447", "researcher": {"href": "https://publications.scilifelab.se/researcher/53216ecce7934eb3a4beedb82f318fc5.json"}}, {"family": "Semenets", "given": "Anastasiia", "initials": "A", "orcid": "0000-0002-6223-9506", "researcher": {"href": "https://publications.scilifelab.se/researcher/2dfc8da363494ad683ce39942f8f4303.json"}}, {"family": "Cisneros", "given": "David A", "initials": "DA", "orcid": "0000-0001-9919-0075", "researcher": {"href": "https://publications.scilifelab.se/researcher/19f7a4aba7af436899b5d63f95f0dcda.json"}}, {"family": "Ramstedt", "given": "Madeleine", "initials": "M", "orcid": "0000-0003-2646-8501", "researcher": {"href": "https://publications.scilifelab.se/researcher/f0fb139ad40341fd85e4ba6fe39eb7fe.json"}}], "type": "journal-article", "published": "2020-12-00", "journal": {"title": "Surf Interface Anal", "issn": "0142-2421", "issn-l": null, "volume": "52", "issue": "12", "pages": "792-801"}, "abstract": null, "doi": "10.1002/sia.6854", "pmid": null, "labels": {"Integrated Microscopy Technologies Ume\u00e5": "Service"}, "xrefs": [], "notes": [], "created": "2022-04-01T14:41:47.140Z", "modified": "2022-11-21T15:37:28.363Z"}, {"entity": "publication", "iuid": "a69d55207dec49ddac152536cf0a38fe", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a69d55207dec49ddac152536cf0a38fe.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a69d55207dec49ddac152536cf0a38fe"}}, "title": "Mutation-independent Proteomic Signatures of Pathological Progression in Murine Models of Duchenne Muscular Dystrophy.", "authors": [{"family": "van Westering", "given": "Tirsa L E", "initials": "TLE"}, {"family": "Johansson", "given": "Henrik J", "initials": "HJ"}, {"family": "Hanson", "given": "Britt", "initials": "B"}, {"family": "Coenen-Stass", "given": "Anna M L", "initials": "AML"}, {"family": "Lomonosova", "given": "Yulia", "initials": "Y"}, {"family": "Tanihata", "given": "Jun", "initials": "J"}, {"family": "Motohashi", "given": "Norio", "initials": "N"}, {"family": "Yokota", "given": "Toshifumi", "initials": "T"}, {"family": "Takeda", "given": "Shin'ichi", "initials": "S"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J"}, {"family": "Wood", "given": "Matthew J A", "initials": "MJA"}, {"family": "El Andaloussi", "given": "Samir", "initials": "S"}, {"family": "Aoki", "given": "Yoshitsugu", "initials": "Y"}, {"family": "Roberts", "given": "Thomas C", "initials": "TC"}], "type": "journal article", "published": "2020-12-00", "journal": {"title": "Mol. Cell Proteomics", "issn": "1535-9484", "volume": "19", "issue": "12", "pages": "2047-2068", "issn-l": "1535-9476"}, "abstract": "The absence of the dystrophin protein in Duchenne muscular dystrophy (DMD) results in myofiber fragility and a plethora of downstream secondary pathologies. Although a variety of experimental therapies are in development, achieving effective treatments for DMD remains exceptionally challenging, not least because the pathological consequences of dystrophin loss are incompletely understood. Here we have performed proteome profiling in tibialis anterior muscles from two murine DMD models (mdx and mdx52) at three ages (8, 16, and 80 weeks of age), all n = 3. High-resolution isoelectric focusing liquid chromatography-tandem MS (HiRIEF-LC-MS/MS) was used to quantify the expression of 4974 proteins across all 27 samples. The two dystrophic models were found to be highly similar, whereas multiple proteins were differentially expressed relative to WT (C57BL/6) controls at each age. Furthermore, 1795 proteins were differentially expressed when samples were pooled across ages and dystrophic strains. These included numerous proteins associated with the extracellular matrix and muscle function that have not been reported previously. Pathway analysis revealed multiple perturbed pathways and predicted upstream regulators, which together are indicative of cross-talk between inflammatory, metabolic, and muscle growth pathways (e.g. TNF, INF\u03b3, NF-\u03baB, SIRT1, AMPK, PGC-1\u03b1, PPARs, ILK, and AKT/PI3K). Upregulation of CAV3, MVP and PAK1 protein expression was validated in dystrophic muscle by Western blot. Furthermore, MVP was upregulated during, but not required for, the differentiation of C2C12 myoblasts suggesting that this protein may affect muscle regeneration. This study provides novel insights into mutation-independent proteomic signatures characteristic of the dystrophic phenotype and its progression with aging.", "doi": "10.1074/mcp.RA120.002345", "pmid": "32994316", "labels": {"Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pii", "key": "S1535-9476(20)60011-1"}, {"db": "pmc", "key": "PMC7710136"}], "notes": [], "created": "2021-12-10T07:00:35.742Z", "modified": "2022-03-29T12:17:23.023Z"}, {"entity": "publication", "iuid": "b60e781bbbf44adb903c7051344daab6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b60e781bbbf44adb903c7051344daab6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b60e781bbbf44adb903c7051344daab6"}}, "title": "Morphological characters and SNP markers suggest hybridization and introgression in sympatric populations of the pleurocarpous mosses Homalothecium lutescens and H. sericeum", "authors": [{"family": "Sawangproh", "given": "Weerachon", "initials": "W"}, {"family": "Lang", "given": "Annick S", "initials": "AS"}, {"family": "Heden\u00e4s", "given": "Lars", "initials": "L"}, {"family": "Cronberg", "given": "Nils", "initials": "N", "orcid": "0000-0002-3369-8420", "researcher": {"href": "https://publications.scilifelab.se/researcher/bb83910f16b84861934f459105f0bc93.json"}}], "type": "journal-article", "published": "2020-12-00", "journal": {"title": "Org Divers Evol", "issn": "1439-6092", "issn-l": null, "volume": "20", "issue": "4", "pages": "619-637"}, "abstract": null, "doi": "10.1007/s13127-020-00456-x", "pmid": null, "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [], "notes": [], "created": "2020-12-10T09:53:40.082Z", "modified": "2021-12-07T13:47:06.801Z"}, {"entity": "publication", "iuid": "1c5fe44325644332be4fc9a626613969", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1c5fe44325644332be4fc9a626613969.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1c5fe44325644332be4fc9a626613969"}}, "title": "Molecular characteristics of eae-positive clinical Shiga toxin-producing Escherichia coli in Sweden.", "authors": [{"family": "Hua", "given": "Ying", "initials": "Y"}, {"family": "Bai", "given": "Xiangning", "initials": "X"}, {"family": "Zhang", "given": "Ji", "initials": "J"}, {"family": "Jernberg", "given": "Cecilia", "initials": "C", "orcid": "0000-0002-1112-5306", "researcher": {"href": "https://publications.scilifelab.se/researcher/dcd7b83a9c0f4e2ab211c26758e86681.json"}}, {"family": "Chromek", "given": "Milan", "initials": "M"}, {"family": "Hansson", "given": "Sverker", "initials": "S"}, {"family": "Frykman", "given": "Anne", "initials": "A"}, {"family": "Yang", "given": "Xi", "initials": "X"}, {"family": "Xiong", "given": "Yanwen", "initials": "Y"}, {"family": "Wan", "given": "Chengsong", "initials": "C"}, {"family": "Matussek", "given": "Andreas", "initials": "A"}], "type": "journal article", "published": "2020-12-00", "journal": {"title": "Emerg Microbes Infect", "issn": "2222-1751", "volume": "9", "issue": "1", "pages": "2562-2570", "issn-l": "2222-1751"}, "abstract": "Shiga toxin (Stx)-producing Escherichia coli (STEC) can cause a wide range of symptoms from asymptomatic carriage, mild diarrhea to bloody diarrhea (BD) and hemolytic uremic syndrome (HUS). Intimin, encoded by the eae gene, also plays a critical role in STEC pathogenesis. Herein, we investigated the prevalence and genetic diversity of eae among clinical STEC isolates from patients with diarrhea, BD, HUS as well as from asymptomatic STEC-positive individuals in Sweden with whole-genome sequencing. We found that 173 out of 239 (72.4%) of clinical STEC strains were eae positive. Six eae subtypes (\u03f51, \u03b31, \u03b23, \u03b8, \u03b6 and \u03c1) were identified eae and its subtype \u03b31 were significantly overrepresented in O157:H7 strains isolated from BD and HUS patients. \u03f51 was associated with O121:H19 and O103:H2 strains, and \u03b23 to O26:H11 strains. The combination of eae subtype \u03b31 and stx subtype (stx 2 or stx 1+stx 2) is more likely to cause severe disease, suggesting the possibility of using eae genotypes in risk assessment of STEC infection. In summary, this study demonstrated a high prevalence of eae in clinical STEC strains and considerable genetic diversity of eae in STEC strains in Sweden from 1994 through 2018, and revealed association between eae subtypes and disease severity.", "doi": "10.1080/22221751.2020.1850182", "pmid": "33179570", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7733975"}], "notes": [], "created": "2021-01-03T10:18:41.946Z", "modified": "2021-11-10T12:44:32.771Z"}, {"entity": "publication", "iuid": "c1bbcbfaa4c642ffbe6f8923aab6bd2a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c1bbcbfaa4c642ffbe6f8923aab6bd2a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c1bbcbfaa4c642ffbe6f8923aab6bd2a"}}, "title": "Methods for isolation and transcriptional profiling of individual cells from the human heart.", "authors": [{"family": "Pimpalwar", "given": "Neha", "initials": "N"}, {"family": "Czuba", "given": "Tomasz", "initials": "T"}, {"family": "Smith", "given": "Maya Landenhed", "initials": "ML"}, {"family": "Nilsson", "given": "Johan", "initials": "J", "orcid": "0000-0001-6860-6090", "researcher": {"href": "https://publications.scilifelab.se/researcher/c07e3381e15b4806b77d1b575e4ddca2.json"}}, {"family": "Gidl\u00f6f", "given": "Olof", "initials": "O"}, {"family": "Smith", "given": "J Gustav", "initials": "JG", "orcid": "0000-0001-6285-9935", "researcher": {"href": "https://publications.scilifelab.se/researcher/26e50df6bb7f4194a52546dbd5652e84.json"}}], "type": "journal article", "published": "2020-12-00", "journal": {"title": "Heliyon", "issn": "2405-8440", "volume": "6", "issue": "12", "pages": "e05810", "issn-l": "2405-8440"}, "abstract": "Global transcriptional profiling of individual cells represents a powerful approach to systematically survey contributions from cell-specific molecular phenotypes to human disease states but requires tissue-specific protocols. Here we sought to comprehensively evaluate protocols for single cell isolation and transcriptional profiling from heart tissue, focusing particularly on frozen tissue which is necessary for study of human hearts at scale.\n\nUsing flow cytometry and high-content screening, we found that enzymatic dissociation of fresh murine heart tissue resulted in a sufficient yield of intact cells while for frozen murine or human heart resulted in low-quality cell suspensions across a range of protocols. These findings were consistent across enzymatic digestion protocols and whether samples were snap-frozen or treated with RNA-stabilizing agents before freezing. In contrast, we show that isolation of cardiac nuclei from frozen hearts results in a high yield of intact nuclei, and leverage expression arrays to show that nuclear transcriptomes reliably represent the cytoplasmic and whole-cell transcriptomes of the major cardiac cell types. Furthermore, coupling of nuclear isolation to PCM1-gated flow cytometry facilitated specific cardiomyocyte depletion, expanding resolution of the cardiac transcriptome beyond bulk tissue transcriptomes which were most strongly correlated with PCM1+ transcriptomes (r = 0.8). We applied these methods to generate a transcriptional catalogue of human cardiac cells by droplet-based RNA-sequencing of 8,460 nuclei from which cellular identities were inferred. Reproducibility of identified clusters was confirmed in an independent biopsy (4,760 additional PCM1- nuclei) from the same human heart.\n\nOur results confirm the validity of single-nucleus but not single-cell isolation for transcriptional profiling of individual cells from frozen heart tissue, and establishes PCM1-gating as an efficient tool for cardiomyocyte depletion. In addition, our results provide a perspective of cell types inferred from single-nucleus transcriptomes that are present in an adult human heart.", "doi": "10.1016/j.heliyon.2020.e05810", "pmid": "33426328", "labels": {"Eukaryotic Single Cell Genomics (ESCG)": "Service"}, "xrefs": [{"db": "pii", "key": "S2405-8440(20)32653-0"}, {"db": "pmc", "key": "PMC7779736"}], "notes": [], "created": "2021-12-02T13:52:27.911Z", "modified": "2022-01-03T09:58:40.529Z"}, {"entity": "publication", "iuid": "3a8b58501bd641d4864a5fcdfb493d87", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3a8b58501bd641d4864a5fcdfb493d87.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3a8b58501bd641d4864a5fcdfb493d87"}}, "title": "Methane potentials and organic matter characterization of wood fibres from pulp and paper mills: The influence of raw material, pulping process and bleaching technique", "authors": [{"family": "Ekstrand", "given": "E M", "initials": "EM", "orcid": "0000-0001-5260-1826", "researcher": {"href": "https://publications.scilifelab.se/researcher/ef4387c4ab354adfa02edecbe3c6147c.json"}}, {"family": "Hedenstr\u00f6m", "given": "M", "initials": "M"}, {"family": "Svensson", "given": "B H", "initials": "BH"}, {"family": "Shakeri Yekta", "given": "S", "initials": "S"}, {"family": "Bj\u00f6rn", "given": "A", "initials": "A"}], "type": "journal-article", "published": "2020-12-00", "journal": {"title": "Biomass and Bioenergy", "issn": "0961-9534", "volume": "143", "issue": null, "pages": "105824", "issn-l": null}, "abstract": null, "doi": "10.1016/j.biombioe.2020.105824", "pmid": null, "labels": {"Swedish NMR Centre": "Collaborative"}, "xrefs": [], "notes": [], "created": "2020-11-24T20:26:41.107Z", "modified": "2025-10-17T13:03:56.460Z"}, {"entity": "publication", "iuid": "c04a689a952745a7b20584f2293eece0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c04a689a952745a7b20584f2293eece0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c04a689a952745a7b20584f2293eece0"}}, "title": "Metagenome assembled-genomes reveal similar functional profiles of CPR/Patescibacteria phyla in soils.", "authors": [{"family": "Nascimento Lemos", "given": "Leandro", "initials": "L", "orcid": "0000-0002-0898-568X", "researcher": {"href": "https://publications.scilifelab.se/researcher/2d27ac7aa5124a0e891272bb955adde4.json"}}, {"family": "Manoharan", "given": "Lokeshwaran", "initials": "L", "orcid": "0000-0001-9751-5745", "researcher": {"href": "https://publications.scilifelab.se/researcher/000321fd81b9457db66140246bbd9066.json"}}, {"family": "William Mendes", "given": "Lucas", "initials": "L", "orcid": "0000-0003-0980-7006", "researcher": {"href": "https://publications.scilifelab.se/researcher/205efe9eca574e0fad7434a25b3bc028.json"}}, {"family": "Monteiro Venturini", "given": "Andressa", "initials": "A"}, {"family": "Satler Pylro", "given": "Victor", "initials": "V", "orcid": "0000-0003-2154-9150", "researcher": {"href": "https://publications.scilifelab.se/researcher/384c2ceb3ffb4e39a44a221f9830df60.json"}}, {"family": "Tsai", "given": "Siu Mui", "initials": "SM", "orcid": "0000-0002-3733-6312", "researcher": {"href": "https://publications.scilifelab.se/researcher/1a40fb3d3e4d4b15b5a34c3d797ace3a.json"}}], "type": "journal article", "published": "2020-12-00", "journal": {"volume": "12", "issn": "1758-2229", "issue": "6", "title": "Environ Microbiol Rep", "pages": "651-655", "issn-l": "1758-2229"}, "abstract": "Soil microbiome is one of the most heterogeneous biological systems. State-of-the-art molecular approaches such as those based on single-amplified genomes (SAGs) and metagenome assembled-genomes (MAGs) are now improving our capacity for disentailing soil microbial-mediated processes. Here, we analysed publicly available datasets of soil microbial genomes and MAG's reconstructed from the Amazon's tropical soil (primary forest and pasture) and active layer of permafrost, aiming to evaluate their genome size. Our results suggest that the Candidate Phyla Radiation (CPR)/Patescibacteria phyla have genomes with an average size fourfold smaller than the mean identified in the RefSoil database, which lacks any representative of this phylum. Also, by analysing the potential metabolism of 888 soil microbial genomes, we show that CPR/Patescibacteria representatives share similar functional profiles, but different from other microbial phyla and are frequently neglected in the soil microbial surveys. Finally, we argue that the use of MAGs may be a better choice over SAGs to expand the soil microbial databases, like RefSoil.", "doi": "10.1111/1758-2229.12880", "pmid": "32815317", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [], "notes": [], "created": "2020-09-10T13:39:31.755Z", "modified": "2024-01-16T13:48:41.226Z"}, {"entity": "publication", "iuid": "7314485325a6426d9d9a4add5c54715a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7314485325a6426d9d9a4add5c54715a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7314485325a6426d9d9a4add5c54715a"}}, "title": "Heterozygous variants in DCC: Beyond congenital mirror movements.", "authors": [{"family": "Thams", "given": "Sebastian", "initials": "S"}, {"family": "Islam", "given": "Mominul", "initials": "M"}, {"family": "Lindefeldt", "given": "Marie", "initials": "M"}, {"family": "Nordgren", "given": "Ann", "initials": "A"}, {"family": "Granberg", "given": "Tobias", "initials": "T"}, {"family": "Tesi", "given": "Bianca", "initials": "B"}, {"family": "Barbany", "given": "Gisela", "initials": "G"}, {"family": "Nilsson", "given": "Daniel", "initials": "D"}, {"family": "Paucar", "given": "Martin", "initials": "M", "orcid": "0000-0003-3735-1480", "researcher": {"href": "https://publications.scilifelab.se/researcher/bbc592904eb5402ea48a624471d4b939.json"}}], "type": "journal article", "published": "2020-12-00", "journal": {"title": "Neurol Genet", "issn": "2376-7839", "volume": "6", "issue": "6", "pages": "e526", "issn-l": "2376-7839"}, "abstract": "To perform a comprehensive characterization of a cohort of patients with congenital mirror movements (CMMs) in Sweden.\n\nClinical examination with the Woods and Teuber scale for mirror movements (MMs), neuroimaging, navigated transcranial magnetic stimulation (nTMS), and massive parallel sequencing (MPS) were applied.\n\nThe cohort is ethnically diverse and includes a total of 7 patients distributed in 2 families and 2 sporadic cases. The degree of MMs was variable in this cohort. MPS revealed 2 novel heterozygous frameshift variants in DCC netrin 1 receptor (DCC). Two siblings harboring the pathogenic variant in c.1466_1476del display a complex syndrome featuring MMs and in 1 case receptive-expressive language disorder, chorea, epilepsy, and agenesis of the corpus callosum. The second DCC variant, c.1729delG, was associated with a typical benign CMM phenotype. No variants in DCC, NTN1, RAD51, or DNAL4 were found for the 2 sporadic CMM cases. However, one of these sporadic cases had concomitant high-risk myelodysplastic syndrome and a homozygous variant in ERCC excision repair like 2 (ERCC6L2). Reorganized corticospinal projection patterns to upper extremities were demonstrated with nTMS.\n\nThe presence of chorea expands the clinical spectrum of syndromes associated with variants in DCC. Biallelic pathogenic variants in ERCC6L2 cause bone marrow failure, but a potential association with CMM remains to be studied in larger cohorts.", "doi": "10.1212/NXG.0000000000000526", "pmid": "33209984", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "NG2020013177"}, {"db": "pmc", "key": "PMC7670573"}], "notes": [], "created": "2021-11-20T12:19:31.452Z", "modified": "2021-11-20T12:19:31.511Z"}, {"entity": "publication", "iuid": "794a7c23da0549009ddf423b8184e00c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/794a7c23da0549009ddf423b8184e00c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/794a7c23da0549009ddf423b8184e00c"}}, "title": "Glycocholic acid and butyrate synergistically increase vitamin D-induced calcium uptake in Caco-2 intestinal epithelial cell monolayers.", "authors": [{"family": "Casselbrant", "given": "Anna", "initials": "A"}, {"family": "F\u00e4ndriks", "given": "Lars", "initials": "L"}, {"family": "Wallenius", "given": "Ville", "initials": "V"}], "type": "journal article", "published": "2020-12-00", "journal": {"title": "Bone Rep", "issn": "2352-1872", "volume": "13", "pages": "100294", "issn-l": null}, "abstract": "Roux-en-Y gastric bypass (RYGB) substantially decreases intestinal calcium absorption and may eventually lead to bone resorption. This is likely a consequence of bile diversion from the alimentary limb, as the presence of bile seems necessary for vitamin D-mediated calcium uptake. We recently suggested that the mediating mechanism may be a down-regulation of the vitamin D co-activator heat-shock protein (Hsp)90\u03b2. Recent evidence suggests that vitamin D may have effects on both active and passive calcium absorption.\n\nTo identify mechanisms in vitro that may be responsible for the decreased calcium absorption after RYGB. We hypothesized that bile, alone or in concert with nutritional compounds, could be of importance.\n\nCaco-2 cells were grown confluent on semi-permeable membranes in a double-chamber setup to mimic small intestinal mucosa. The effect of bile acids chenodeoxycholic, lithocholic, glycocholic and taurocholic acid, with and without the addition of the fatty-acid butyrate, were tested for their effects on Hsp90\u03b2 expression and active and passive calcium-flux monitored using radioactive 45Ca.\n\nWe initially found that whole human bile, but only together with the fatty acid butyrate, potently induced Hsp90\u03b2 expression. In line with this, a single bile acid, e.g. glycocholic acid (GCA), in combination with butyrate, increased Hsp90\u03b2 expression (40 \u00b1 13% vs. GCA, butyrate or vehicle alone; p < 0,001; n = 14-25). Further, this combination together with vitamin D increased the passive gradient-driven flux of calcium, compared to stimulation with vitamin D alone or in combination with either GCA or butyrate (880 \u00b1 217% vs. vitamin D and GCA or butyrate, or vitamin D only; p = 0,01-0.006; n = 5-11). Surprisingly, this combination had no effect on active calcium transport in the absence of calcium gradient.\n\nThe combination of GCA and butyrate increased gradient-driven calcium uptake up to 9-fold in Caco-2 intestinal epithelial cells, but had no effect on active calcium absorption. This effect was mediated via the vitamin D receptor co-activator Hsp90\u03b2.", "doi": "10.1016/j.bonr.2020.100294", "pmid": "32715032", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7371747"}, {"db": "pii", "key": "S2352-1872(20)30054-1"}], "notes": [], "created": "2023-02-16T08:05:39.517Z", "modified": "2023-02-16T08:05:39.519Z"}, {"entity": "publication", "iuid": "0a90b284f37043df85ba89a51ee5cc2a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0a90b284f37043df85ba89a51ee5cc2a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0a90b284f37043df85ba89a51ee5cc2a"}}, "title": "Genome-wide association study of angioedema induced by angiotensin-converting enzyme inhibitor and angiotensin receptor blocker treatment.", "authors": [{"family": "Rasmussen", "given": "Eva Rye", "initials": "ER"}, {"family": "Hallberg", "given": "P\u00e4r", "initials": "P"}, {"family": "Baranova", "given": "Ekaterina V", "initials": "EV"}, {"family": "Eriksson", "given": "Niclas", "initials": "N"}, {"family": "Karawajczyk", "given": "Malgorzata", "initials": "M"}, {"family": "Johansson", "given": "Caroline", "initials": "C"}, {"family": "Cavalli", "given": "Marco", "initials": "M"}, {"family": "Maroteau", "given": "Cyrielle", "initials": "C"}, {"family": "Veluchamy", "given": "Abirami", "initials": "A"}, {"family": "Islander", "given": "Gunilla", "initials": "G"}, {"family": "Hugosson", "given": "Svante", "initials": "S"}, {"family": "Terreehorst", "given": "Ingrid", "initials": "I"}, {"family": "Asselbergs", "given": "Folkert W", "initials": "FW", "orcid": "0000-0002-1692-8669", "researcher": {"href": "https://publications.scilifelab.se/researcher/7037429ef1304bdaabd837d242b1e6f5.json"}}, {"family": "Norling", "given": "Pia", "initials": "P"}, {"family": "Johansson", "given": "Hans-Erik", "initials": "HE"}, {"family": "Kohnke", "given": "Hugo", "initials": "H"}, {"family": "Syv\u00e4nen", "given": "Ann-Christine", "initials": "AC", "orcid": "0000-0002-9681-9146", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7012e35025543379380cb90efd71243.json"}}, {"family": "Siddiqui", "given": "Moneeza K", "initials": "MK"}, {"family": "Lang", "given": "Chim C", "initials": "CC"}, {"family": "Magnusson", "given": "Patrik K E", "initials": "PKE", "orcid": "0000-0002-7315-7899", "researcher": {"href": "https://publications.scilifelab.se/researcher/b277b6387de142bbab91fad82d9eff09.json"}}, {"family": "Yue", "given": "Qun-Ying", "initials": "QY"}, {"family": "Wadelius", "given": "Claes", "initials": "C"}, {"family": "von Buchwald", "given": "Christian", "initials": "C"}, {"family": "Bygum", "given": "Anette", "initials": "A"}, {"family": "Alfirevic", "given": "Ana", "initials": "A"}, {"family": "Maitland-van der Zee", "given": "Anke H", "initials": "AH"}, {"family": "Palmer", "given": "Colin N A", "initials": "CNA", "orcid": "0000-0002-6415-6560", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a0f019dcb7a453a84480953a5514dd5.json"}}, {"family": "Wadelius", "given": "Mia", "initials": "M", "orcid": "0000-0002-6368-2622", "researcher": {"href": "https://publications.scilifelab.se/researcher/ec07b9869a1f4b77b734c5dc567dc630.json"}}], "type": "journal article", "published": "2020-12-00", "journal": {"title": "Pharmacogenomics J.", "issn": "1473-1150", "volume": "20", "issue": "6", "pages": "770-783", "issn-l": "1470-269X"}, "abstract": "Angioedema in the mouth or upper airways is a feared adverse reaction to angiotensin-converting enzyme inhibitor (ACEi) and angiotensin receptor blocker (ARB) treatment, which is used for hypertension, heart failure and diabetes complications. This candidate gene and genome-wide association study aimed to identify genetic variants predisposing to angioedema induced by these drugs. The discovery cohort consisted of 173 cases and 4890 controls recruited in Sweden. In the candidate gene analysis, ETV6, BDKRB2, MME, and PRKCQ were nominally associated with angioedema (p < 0.05), but did not pass Bonferroni correction for multiple testing (p < 2.89 \u00d7 10-5). In the genome-wide analysis, intronic variants in the calcium-activated potassium channel subunit alpha-1 (KCNMA1) gene on chromosome 10 were significantly associated with angioedema (p < 5 \u00d7 10-8). Whilst the top KCNMA1 hit was not significant in the replication cohort (413 cases and 599 ACEi-exposed controls from the US and Northern Europe), a meta-analysis of the replication and discovery cohorts (in total 586 cases and 1944 ACEi-exposed controls) revealed that each variant allele increased the odds of experiencing angioedema 1.62 times (95% confidence interval 1.05-2.50, p = 0.030). Associated KCNMA1 variants are not known to be functional, but are in linkage disequilibrium with variants in transcription factor binding sites active in relevant tissues. In summary, our data suggest that common variation in KCNMA1 is associated with risk of angioedema induced by ACEi or ARB treatment. Future whole exome or genome sequencing studies will show whether rare variants in KCNMA1 or other genes contribute to the risk of ACEi- and ARB-induced angioedema.", "doi": "10.1038/s41397-020-0165-2", "pmid": "32080354", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41397-020-0165-2"}, {"db": "pmc", "key": "PMC7674154"}], "notes": [], "created": "2020-02-27T09:21:01.759Z", "modified": "2024-01-16T13:48:41.233Z"}, {"entity": "publication", "iuid": "92d63630ecd7441b85eecaa4c4b48a08", "links": {"self": {"href": "https://publications.scilifelab.se/publication/92d63630ecd7441b85eecaa4c4b48a08.json"}, "display": {"href": "https://publications.scilifelab.se/publication/92d63630ecd7441b85eecaa4c4b48a08"}}, "title": "Genetic Studies of Leptin Concentrations Implicate Leptin in the Regulation of Early Adiposity.", "authors": [{"family": "Yaghootkar", "given": "Hanieh", "initials": "H", "orcid": "0000-0001-9672-9477", "researcher": {"href": "https://publications.scilifelab.se/researcher/2202b216df584f7cb4a4cf3f38ba2cec.json"}}, {"family": "Zhang", "given": "Yiying", "initials": "Y"}, {"family": "Spracklen", "given": "Cassandra N", "initials": "CN"}, {"family": "Karaderi", "given": "Tugce", "initials": "T"}, {"family": "Huang", "given": "Lam Opal", "initials": "LO"}, {"family": "Bradfield", "given": "Jonathan", "initials": "J"}, {"family": "Schurmann", "given": "Claudia", "initials": "C"}, {"family": "Fine", "given": "Rebecca S", "initials": "RS"}, {"family": "Preuss", "given": "Michael H", "initials": "MH"}, {"family": "Kutalik", "given": "Zoltan", "initials": "Z"}, {"family": "Wittemans", "given": "Laura B L", "initials": "LBL"}, {"family": "Lu", "given": "Yingchang", "initials": "Y"}, {"family": "Metz", "given": "Sophia", "initials": "S"}, {"family": "Willems", "given": "Sara M", "initials": "SM"}, {"family": "Li-Gao", "given": "Ruifang", "initials": "R"}, {"family": "Grarup", "given": "Niels", "initials": "N"}, {"family": "Wang", "given": "Shuai", "initials": "S"}, {"family": "Molnos", "given": "Sophie", "initials": "S"}, {"family": "Sandoval-Z\u00e1rate", "given": "Am\u00e9rica A", "initials": "AA"}, {"family": "Nalls", "given": "Mike A", "initials": "MA"}, {"family": "Lange", "given": "Leslie A", "initials": "LA"}, {"family": "Haesser", "given": "Jeffrey", "initials": "J"}, {"family": "Guo", "given": "Xiuqing", "initials": "X"}, {"family": "Lyytik\u00e4inen", "given": "Leo-Pekka", "initials": "LP"}, {"family": "Feitosa", "given": "Mary F", "initials": "MF"}, {"family": "Sitlani", "given": "Colleen M", "initials": "CM"}, {"family": "Venturini", "given": "Cristina", "initials": "C"}, {"family": "Mahajan", "given": "Anubha", "initials": "A"}, {"family": "Kacprowski", "given": "Tim", "initials": "T"}, {"family": "Wang", "given": "Carol A", "initials": "CA"}, {"family": "Chasman", "given": "Daniel I", "initials": "DI"}, {"family": "Amin", "given": "Najaf", "initials": "N"}, {"family": "Broer", "given": "Linda", "initials": "L"}, {"family": "Robertson", "given": "Neil", "initials": "N"}, {"family": "Young", "given": "Kristin L", "initials": "KL"}, {"family": "Allison", "given": "Matthew", "initials": "M"}, {"family": "Auer", "given": "Paul L", "initials": "PL"}, {"family": "Bl\u00fcher", "given": "Matthias", "initials": "M"}, {"family": "Borja", "given": "Judith B", "initials": "JB"}, {"family": "Bork-Jensen", "given": "Jette", "initials": "J"}, {"family": "Carrasquilla", "given": "Germ\u00e1n D", "initials": "GD"}, {"family": "Christofidou", "given": "Paraskevi", "initials": "P"}, {"family": "Demirkan", "given": "Ayse", "initials": "A"}, {"family": "Doege", "given": "Claudia A", "initials": "CA"}, {"family": "Garcia", "given": "Melissa E", "initials": "ME"}, {"family": "Graff", "given": "Mariaelisa", "initials": "M"}, {"family": "Guo", "given": "Kaiying", "initials": "K"}, {"family": "Hakonarson", "given": "Hakon", "initials": "H"}, {"family": "Hong", "given": "Jaeyoung", "initials": "J"}, {"family": "Ida Chen", "given": "Yii-Der", "initials": "YD"}, {"family": "Jackson", "given": "Rebecca", "initials": "R"}, {"family": "Jakupovi\u0107", "given": "Hermina", "initials": "H"}, {"family": "Jousilahti", "given": "Pekka", "initials": "P"}, {"family": "Justice", "given": "Anne E", "initials": "AE"}, {"family": "K\u00e4h\u00f6nen", "given": "Mika", "initials": "M"}, {"family": "Kizer", "given": "Jorge R", "initials": "JR"}, {"family": "Kriebel", "given": "Jennifer", "initials": "J"}, {"family": "LeDuc", "given": "Charles A", "initials": "CA"}, {"family": "Li", "given": "Jin", "initials": "J"}, {"family": "Lind", "given": "Lars", "initials": "L"}, {"family": "Luan", "given": "Jian'an", "initials": "J"}, {"family": "Mackey", "given": "David A", "initials": "DA"}, {"family": "Mangino", "given": "Massimo", "initials": "M"}, {"family": "M\u00e4nnist\u00f6", "given": "Satu", "initials": "S"}, {"family": "Martin Carli", "given": "Jayne F", "initials": "JF"}, {"family": "Medina-Gomez", "given": "Carolina", "initials": "C"}, {"family": "Mook-Kanamori", "given": "Dennis O", "initials": "DO"}, {"family": "Morris", "given": "Andrew P", "initials": "AP"}, {"family": "de Mutsert", "given": "Ren\u00e9e", "initials": "R"}, {"family": "Nauck", "given": "Matthias", "initials": "M"}, {"family": "Prokic", "given": "Ivana", "initials": "I"}, {"family": "Pennell", "given": "Craig E", "initials": "CE"}, {"family": "Pradhan", "given": "Arund D", "initials": "AD"}, {"family": "Psaty", "given": "Bruce M", "initials": "BM"}, {"family": "Raitakari", "given": "Olli T", "initials": "OT"}, {"family": "Scott", "given": "Robert A", "initials": "RA"}, {"family": "Skaaby", "given": "Tea", "initials": "T"}, {"family": "Strauch", "given": "Konstantin", "initials": "K"}, {"family": "Taylor", "given": "Kent D", "initials": "KD"}, {"family": "Teumer", "given": "Alexander", "initials": "A"}, {"family": "Uitterlinden", "given": "Andre G", "initials": "AG"}, {"family": "Wu", "given": "Ying", "initials": "Y"}, {"family": "Yao", "given": "Jie", "initials": "J"}, {"family": "Walker", "given": "Mark", "initials": "M"}, {"family": "North", "given": "Kari E", "initials": "KE"}, {"family": "Kovacs", "given": "Peter", "initials": "P"}, {"family": "Ikram", "given": "M Arfan", "initials": "MA"}, {"family": "van Duijn", "given": "Cornelia M", "initials": "CM"}, {"family": "Ridker", "given": "Paul M", "initials": "PM"}, {"family": "Lye", "given": "Stephen", "initials": "S"}, {"family": "Homuth", "given": "Georg", "initials": "G"}, {"family": "Ingelsson", "given": "Erik", "initials": "E"}, {"family": "Spector", "given": "Tim D", "initials": "TD"}, {"family": "McKnight", "given": "Barbara", "initials": "B"}, {"family": "Province", "given": "Michael A", "initials": "MA"}, {"family": "Lehtim\u00e4ki", "given": "Terho", "initials": "T"}, {"family": "Adair", "given": "Linda S", "initials": "LS"}, {"family": "Rotter", "given": "Jerome I", "initials": "JI"}, {"family": "Reiner", "given": "Alexander P", "initials": "AP"}, {"family": "Wilson", "given": "James G", "initials": "JG"}, {"family": "Harris", "given": "Tamara B", "initials": "TB"}, {"family": "Ripatti", "given": "Samuli", "initials": "S"}, {"family": "Grallert", "given": "Harald", "initials": "H"}, {"family": "Meigs", "given": "James B", "initials": "JB"}, {"family": "Salomaa", "given": "Veikko", "initials": "V"}, {"family": "Hansen", "given": "Torben", "initials": "T"}, {"family": "Willems van Dijk", "given": "Ko", "initials": "K"}, {"family": "Wareham", "given": "Nicholas J", "initials": "NJ"}, {"family": "Grant", "given": "Struan F A", "initials": "SFA"}, {"family": "Langenberg", "given": "Claudia", "initials": "C"}, {"family": "Frayling", "given": "Timothy M", "initials": "TM"}, {"family": "Lindgren", "given": "Cecilia M", "initials": "CM"}, {"family": "Mohlke", "given": "Karen L", "initials": "KL"}, {"family": "Leibel", "given": "Rudolph L", "initials": "RL"}, {"family": "Loos", "given": "Ruth J F", "initials": "RJF"}, {"family": "Kilpel\u00e4inen", "given": "Tuomas O", "initials": "TO", "orcid": "0000-0002-8349-3028", "researcher": {"href": "https://publications.scilifelab.se/researcher/d805d86c7bf64a7491bef35e45a14485.json"}}], "type": "journal article", "published": "2020-12-00", "journal": {"title": "Diabetes", "issn": "1939-327X", "volume": "69", "issue": "12", "pages": "2806-2818", "issn-l": "0012-1797"}, "abstract": "Leptin influences food intake by informing the brain about the status of body fat stores. Rare LEP mutations associated with congenital leptin deficiency cause severe early-onset obesity that can be mitigated by administering leptin. However, the role of genetic regulation of leptin in polygenic obesity remains poorly understood. We performed an exome-based analysis in up to 57,232 individuals of diverse ancestries to identify genetic variants that influence adiposity-adjusted leptin concentrations. We identify five novel variants, including four missense variants, in LEP, ZNF800, KLHL31, and ACTL9, and one intergenic variant near KLF14. The missense variant Val94Met (rs17151919) in LEP was common in individuals of African ancestry only, and its association with lower leptin concentrations was specific to this ancestry (P = 2 \u00d7 10-16, n = 3,901). Using in vitro analyses, we show that the Met94 allele decreases leptin secretion. We also show that the Met94 allele is associated with higher BMI in young African-ancestry children but not in adults, suggesting that leptin regulates early adiposity.", "doi": "10.2337/db20-0070", "pmid": "32917775", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pii", "key": "db20-0070"}, {"db": "pmc", "key": "PMC7679778"}, {"db": "figshare", "key": "10.2337/figshare.12933737"}], "notes": [], "created": "2020-10-20T06:59:22.330Z", "modified": "2021-11-10T12:44:35.165Z"}, {"entity": "publication", "iuid": "06bdda0e02974b29a11b5fc22fa91b3b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/06bdda0e02974b29a11b5fc22fa91b3b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/06bdda0e02974b29a11b5fc22fa91b3b"}}, "title": "Genetic Predisposition to Coronary Artery Disease in Type 2 Diabetes Mellitus.", "authors": [{"family": "van Zuydam", "given": "Natalie R", "initials": "NR", "orcid": "0000-0002-9809-1398", "researcher": {"href": "https://publications.scilifelab.se/researcher/defa68cc40734fcdaffd7ba0aaad72b8.json"}}, {"family": "Ladenvall", "given": "Claes", "initials": "C", "orcid": "0000-0002-7501-6598", "researcher": {"href": "https://publications.scilifelab.se/researcher/4c5c362dc308476195eb55d2e588ba60.json"}}, {"family": "Voight", "given": "Benjamin F", "initials": "BF", "orcid": "0000-0002-6205-9994", "researcher": {"href": "https://publications.scilifelab.se/researcher/d3d9e9de96ee4983ba97efc14eb3d79b.json"}}, {"family": "Strawbridge", "given": "Rona J", "initials": "RJ", "orcid": "0000-0001-8506-3585", "researcher": {"href": "https://publications.scilifelab.se/researcher/8ac5060a3b37466dae002d4ad8f4d0ac.json"}}, {"family": "Fernandez-Tajes", "given": "Juan", "initials": "J", "orcid": "0000-0003-1515-2421", "researcher": {"href": "https://publications.scilifelab.se/researcher/dad51251fc8d42f793e4c991c4102667.json"}}, {"family": "Rayner", "given": "N William", "initials": "NW", "orcid": "0000-0003-0510-4792", "researcher": {"href": "https://publications.scilifelab.se/researcher/0e3c7e5bd20348629ba3fe232fc2bcd2.json"}}, {"family": "Robertson", "given": "Neil R", "initials": "NR"}, {"family": "Mahajan", "given": "Anubha", "initials": "A"}, {"family": "Vlachopoulou", "given": "Efthymia", "initials": "E"}, {"family": "Goel", "given": "Anuj", "initials": "A", "orcid": "0000-0003-2307-4021", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f16d9d2e2164938a12b027326c21316.json"}}, {"family": "Kleber", "given": "Marcus E", "initials": "ME"}, {"family": "Nelson", "given": "Christopher P", "initials": "CP"}, {"family": "Kwee", "given": "Lydia Coulter", "initials": "LC", "orcid": "0000-0002-6997-8571", "researcher": {"href": "https://publications.scilifelab.se/researcher/aa16042af5d84f11927203fc564e8fcb.json"}}, {"family": "Esko", "given": "T\u00f5nu", "initials": "T", "orcid": "0000-0003-1982-6569", "researcher": {"href": "https://publications.scilifelab.se/researcher/d72619c1e29d44e8b8454902d2af8d9e.json"}}, {"family": "Mihailov", "given": "Evelin", "initials": "E"}, {"family": "M\u00e4gi", "given": "Reedik", "initials": "R", "orcid": "0000-0002-2964-6011", "researcher": {"href": "https://publications.scilifelab.se/researcher/61f337c26b414b8fa30bf0fdb77368a1.json"}}, {"family": "Milani", "given": "Lili", "initials": "L", "orcid": "0000-0002-5323-3102", "researcher": {"href": "https://publications.scilifelab.se/researcher/dec8d00c4b9d43458c5c895b164695d5.json"}}, {"family": "Fischer", "given": "Krista", "initials": "K", "orcid": "0000-0002-3521-0599", "researcher": {"href": "https://publications.scilifelab.se/researcher/bcd45c97a9c2450c9c88adbd83d36b24.json"}}, {"family": "Kanoni", "given": "Stavroula", "initials": "S", "orcid": "0000-0002-1691-9615", "researcher": {"href": "https://publications.scilifelab.se/researcher/95f9c5fce1fe44719ef772eda9a4f5e4.json"}}, {"family": "Kumar", "given": "Jitender", "initials": "J"}, {"family": "Song", "given": "Ci", "initials": "C"}, {"family": "Hartiala", "given": "Jaana A", "initials": "JA", "orcid": "0000-0003-4883-9318", "researcher": {"href": "https://publications.scilifelab.se/researcher/f39400df71774cf8ae408eccbe34d981.json"}}, {"family": "Pedersen", "given": "Nancy L", "initials": "NL", "orcid": "0000-0001-8057-3543", "researcher": {"href": "https://publications.scilifelab.se/researcher/cbee4e5f6d10460cac50f00ee92d5bdf.json"}}, {"family": "Perola", "given": "Markus", "initials": "M", "orcid": "0000-0003-4842-1667", "researcher": {"href": "https://publications.scilifelab.se/researcher/ef3cdf94ecb543f1a449a7704f8be7b2.json"}}, {"family": "Gieger", "given": "Christian", "initials": "C"}, {"family": "Peters", "given": "Annette", "initials": "A", "orcid": "0000-0001-6645-0985", "researcher": {"href": "https://publications.scilifelab.se/researcher/05465e52a0f6412e81752d2249af30de.json"}}, {"family": "Qu", "given": "Liming", "initials": "L"}, {"family": "Willems", "given": "Sara M", "initials": "SM", "orcid": "0000-0002-6803-3007", "researcher": {"href": "https://publications.scilifelab.se/researcher/307c8a9b3ab54ab586c7b000c110e76b.json"}}, {"family": "Doney", "given": "Alex S F", "initials": "ASF"}, {"family": "Morris", "given": "Andrew D", "initials": "AD"}, {"family": "Zheng", "given": "Yan", "initials": "Y", "orcid": "0000-0003-1129-3147", "researcher": {"href": "https://publications.scilifelab.se/researcher/c0baf9bc398345709fcfe2f635c6d443.json"}}, {"family": "Sesti", "given": "Giorgio", "initials": "G", "orcid": "0000-0002-1618-7688", "researcher": {"href": "https://publications.scilifelab.se/researcher/3c564dce3a584837a595ad7c9630092d.json"}}, {"family": "Hu", "given": "Frank B", "initials": "FB", "orcid": "0000-0002-8233-6274", "researcher": {"href": "https://publications.scilifelab.se/researcher/8cdf552612da400a9b3d72aaed260aa9.json"}}, {"family": "Qi", "given": "Lu", "initials": "L", "orcid": "0000-0002-8041-7791", "researcher": {"href": "https://publications.scilifelab.se/researcher/14b5a04081604f12859bb18b5e7c0f38.json"}}, {"family": "Laakso", "given": "Markku", "initials": "M", "orcid": "0000-0002-3394-7749", "researcher": {"href": "https://publications.scilifelab.se/researcher/13d8518be25141a296d7f2df5cccb4ee.json"}}, {"family": "Thorsteinsdottir", "given": "Unnur", "initials": "U"}, {"family": "Grallert", "given": "Harald", "initials": "H"}, {"family": "van Duijn", "given": "Cornelia", "initials": "C", "orcid": "0000-0002-2374-9204", "researcher": {"href": "https://publications.scilifelab.se/researcher/354ccf94e95f40da96e61c89a0a60adb.json"}}, {"family": "Reilly", "given": "Muredach P", "initials": "MP", "orcid": "0000-0002-3035-9386", "researcher": {"href": "https://publications.scilifelab.se/researcher/de249cb6c3774f04985a39ca9828b97e.json"}}, {"family": "Ingelsson", "given": "Erik", "initials": "E"}, {"family": "Deloukas", "given": "Panos", "initials": "P", "orcid": "0000-0001-9251-070X", "researcher": {"href": "https://publications.scilifelab.se/researcher/eb59dbd2f2204d41b801c41188611a9e.json"}}, {"family": "Kathiresan", "given": "Sek", "initials": "S", "orcid": "0000-0002-3711-7101", "researcher": {"href": "https://publications.scilifelab.se/researcher/58fd968293e94da49c506c743a74222e.json"}}, {"family": "Metspalu", "given": "Andres", "initials": "A", "orcid": "0000-0002-3718-796X", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd553a77a5a54258b4a4701f0e70a3f8.json"}}, {"family": "Shah", "given": "Svati H", "initials": "SH"}, {"family": "Sinisalo", "given": "Juha", "initials": "J", "orcid": "0000-0002-0169-5137", "researcher": {"href": "https://publications.scilifelab.se/researcher/6fde24cdfda24aed83d888da0d9b6811.json"}}, {"family": "Salomaa", "given": "Veikko", "initials": "V", "orcid": "0000-0001-7563-5324", "researcher": {"href": "https://publications.scilifelab.se/researcher/f2396c578c254e39b66538c3033c9ce9.json"}}, {"family": "Hamsten", "given": "Anders", "initials": "A"}, {"family": "Samani", "given": "Nilesh J", "initials": "NJ", "orcid": "0000-0002-3286-8133", "researcher": {"href": "https://publications.scilifelab.se/researcher/2227aaf274e8424f8408318f336f3bf1.json"}}, {"family": "M\u00e4rz", "given": "Winfried", "initials": "W"}, {"family": "Hazen", "given": "Stanley L", "initials": "SL", "orcid": "0000-0001-7124-6639", "researcher": {"href": "https://publications.scilifelab.se/researcher/abce9cd916c94667a73bc348ede57a01.json"}}, {"family": "Watkins", "given": "Hugh", "initials": "H", "orcid": "0000-0002-5287-9016", "researcher": {"href": "https://publications.scilifelab.se/researcher/7ea10989397546f9a027f88bd491bb8b.json"}}, {"family": "Saleheen", "given": "Danish", "initials": "D"}, {"family": "Morris", "given": "Andrew P", "initials": "AP"}, {"family": "Colhoun", "given": "Helen M", "initials": "HM", "orcid": "0000-0002-8345-3288", "researcher": {"href": "https://publications.scilifelab.se/researcher/e79cb60e3d734232b7cfad20c4f1c13e.json"}}, {"family": "Groop", "given": "Leif", "initials": "L"}, {"family": "McCarthy", "given": "Mark I", "initials": "MI", "orcid": "0000-0002-4393-0510", "researcher": {"href": "https://publications.scilifelab.se/researcher/5e44f4b1ca3a49cb8f83450ef9482e91.json"}}, {"family": "Palmer", "given": "Colin N A", "initials": "CNA", "orcid": "0000-0002-6415-6560", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a0f019dcb7a453a84480953a5514dd5.json"}}, {"family": "SUMMIT Steering Committee; CARDIOGRAMplusC4D Steering Committee*", "given": "", "initials": ""}], "type": "journal article", "published": "2020-12-00", "journal": {"title": "Circ Genom Precis Med", "issn": "2574-8300", "issn-l": "2574-8300", "volume": "13", "issue": "6", "pages": "e002769"}, "abstract": "Coronary artery disease (CAD) is accelerated in subjects with type 2 diabetes mellitus (T2D).\r\n\r\nTo test whether this reflects differential genetic influences on CAD risk in subjects with T2D, we performed a systematic assessment of genetic overlap between CAD and T2D in 66 643 subjects (27 708 with CAD and 24 259 with T2D). Variants showing apparent association with CAD in stratified analyses or evidence of interaction were evaluated in a further 117 787 subjects (16 694 with CAD and 11 537 with T2D).\r\n\r\nNone of the previously characterized CAD loci was found to have specific effects on CAD in T2D individuals, and a genome-wide interaction analysis found no new variants for CAD that could be considered T2D specific. When we considered the overall genetic correlations between CAD and its risk factors, we found no substantial differences in these relationships by T2D background.\r\n\r\nThis study found no evidence that the genetic architecture of CAD differs in those with T2D compared with those without T2D.", "doi": "10.1161/CIRCGEN.119.002769", "pmid": "33321069", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7748049"}], "notes": [], "created": "2021-01-07T17:01:51.462Z", "modified": "2021-12-07T13:47:48.005Z"}, {"entity": "publication", "iuid": "1ad131dd022d484f84ca9b9dcb288a09", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1ad131dd022d484f84ca9b9dcb288a09.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1ad131dd022d484f84ca9b9dcb288a09"}}, "title": "Features of increased malignancy in eosinophilic clear cell renal cell carcinoma.", "authors": [{"family": "Nilsson", "given": "Hel\u00e9n", "initials": "H"}, {"family": "Lindgren", "given": "David", "initials": "D"}, {"family": "Axelson", "given": "H\u00e5kan", "initials": "H"}, {"family": "Brueffer", "given": "Christian", "initials": "C", "orcid": "0000-0002-3826-0989", "researcher": {"href": "https://publications.scilifelab.se/researcher/6bf6758bd7a54626bdf3b82888431296.json"}}, {"family": "Saal", "given": "Lao H", "initials": "LH"}, {"family": "Lundgren", "given": "Jaana", "initials": "J"}, {"family": "Johansson", "given": "Martin E", "initials": "ME", "orcid": "0000-0001-8510-3102", "researcher": {"href": "https://publications.scilifelab.se/researcher/b85588d272854ff2a9d6c4e364529971.json"}}], "type": "journal article", "published": "2020-12-00", "journal": {"title": "J. Pathol.", "issn": "1096-9896", "issn-l": "0022-3417", "volume": "252", "issue": "4", "pages": "384-397"}, "abstract": "Clear cell renal cell carcinoma (ccRCC) is the most common form of renal cancer. Due to inactivation of the von Hippel-Lindau tumour suppressor, the hypoxia-inducible transcription factors (HIFs) are constitutively activated in these tumours, resulting in a pseudo-hypoxic phenotype. The HIFs induce the expression of genes involved in angiogenesis and cell survival, but they also reset the cellular metabolism to protect cells from oxygen and nutrient deprivation. ccRCC tumours are highly vascularized and the cytoplasm of the cancer cells is filled with lipid droplets and glycogen, resulting in the histologically distinctive pale (clear) cytoplasm. Intratumoural heterogeneity may occur, and in some tumours, areas with granular, eosinophilic cytoplasm are found. Little is known regarding these traits and how they relate to the coexistent clear cell component, yet eosinophilic ccRCC is associated with higher grade and clinically more aggressive tumours. In this study, we have for the first time performed RNA sequencing comparing histologically verified clear cell and eosinophilic areas from ccRCC tissue, aiming to analyse the characteristics of these cell types. Findings from RNA sequencing were confirmed by immunohistochemical staining of biphasic ccRCC. We found that the eosinophilic phenotype displayed a higher proliferative drive and lower differentiation, and we confirmed a correlation to tumours of higher stage. We further identified mutations of the tumour suppressor p53 (TP53) exclusively in the eosinophilic ccRCC component, where mTORC1 activity was also elevated. Also, eosinophilic areas were less vascularized, yet harboured more abundant infiltrating immune cells. The cytoplasm of clear cell ccRCC cells was filled with lipids but had very low mitochondrial content, while the reverse was found in eosinophilic tissue. We herein suggest possible transcriptional mechanisms behind these phenomena. \u00a9 2020 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.", "doi": "10.1002/path.5532", "pmid": "32815150", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7756750"}], "notes": [], "created": "2020-12-07T16:32:32.781Z", "modified": "2024-01-16T13:48:41.254Z"}, {"entity": "publication", "iuid": "d52fe9ba559d4dbcb12811ce80a182df", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d52fe9ba559d4dbcb12811ce80a182df.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d52fe9ba559d4dbcb12811ce80a182df"}}, "title": "Exome Sequencing Reveals Common and Rare Variants in F5 Associated With ACE Inhibitor and Angiotensin Receptor Blocker-Induced Angioedema.", "authors": [{"family": "Maroteau", "given": "Cyrielle", "initials": "C", "orcid": "0000-0001-7816-5508", "researcher": {"href": "https://publications.scilifelab.se/researcher/ebfc9425cb394843ac30847955e53ebe.json"}}, {"family": "Siddiqui", "given": "Moneeza Kalhan", "initials": "MK"}, {"family": "Veluchamy", "given": "Abirami", "initials": "A"}, {"family": "Carr", "given": "Fiona", "initials": "F"}, {"family": "White", "given": "Myra", "initials": "M"}, {"family": "Cassidy", "given": "Andrew J", "initials": "AJ"}, {"family": "Baranova", "given": "Ekaterina V", "initials": "EV"}, {"family": "Rasmussen", "given": "Eva R", "initials": "ER"}, {"family": "Eriksson", "given": "Niclas", "initials": "N", "orcid": "0000-0002-2152-4343", "researcher": {"href": "https://publications.scilifelab.se/researcher/64611a83caba46d597f45371b77de26b.json"}}, {"family": "Bloch", "given": "Katarzyna M", "initials": "KM"}, {"family": "Brown", "given": "Nancy J", "initials": "NJ"}, {"family": "Bygum", "given": "Anette", "initials": "A"}, {"family": "Hallberg", "given": "Par", "initials": "P", "orcid": "0000-0003-3465-3280", "researcher": {"href": "https://publications.scilifelab.se/researcher/968cb3fe072d4ed09739e8be6668d168.json"}}, {"family": "Karawajczyk", "given": "Malgorzata", "initials": "M"}, {"family": "Magnusson", "given": "Patrik K E", "initials": "PKE"}, {"family": "Yue", "given": "Qun-Ying", "initials": "QY"}, {"family": "Syv\u00e4nen", "given": "Ann-Christine", "initials": "AC"}, {"family": "von Buchwald", "given": "Christian", "initials": "C"}, {"family": "Alfirevic", "given": "Ana", "initials": "A"}, {"family": "Maitland-van der Zee", "given": "Anke H", "initials": "AH"}, {"family": "Wadelius", "given": "Mia", "initials": "M", "orcid": "0000-0002-6368-2622", "researcher": {"href": "https://publications.scilifelab.se/researcher/ec07b9869a1f4b77b734c5dc567dc630.json"}}, {"family": "Palmer", "given": "Colin N A", "initials": "CNA"}, {"family": "PREDICTION-ADR", "given": "", "initials": ""}], "type": "journal article", "published": "2020-12-00", "journal": {"title": "Clin. Pharmacol. Ther.", "issn": "1532-6535", "volume": "108", "issue": "6", "pages": "1195-1202", "issn-l": "0009-9236"}, "abstract": "Angioedema occurring in the head and neck region is a rare and sometimes life-threatening adverse reaction to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs). Few studies have investigated the association of common variants with this extreme reaction, but none have explored the combined influence of rare variants yet. Adjudicated cases of ACEI-induced angioedema (ACEI-AE) or ARB-induced angioedema (ARB-AE) and controls were recruited at five different centers. Sequencing of 1,066 samples (408 ACEI-AE, ARB-AE, and 658 controls) was performed using exome-enriched sequence data. A common variant of the F5 gene that causes an increase in blood clotting (rs6025, p.Arg506Gln, also called factor V Leiden), was significantly associated with both ACEI-AE and ARB-AE (odds ratio: 2.85, 95% confidence interval (CI), 1.89-4.25). A burden test analysis of five rare missense variants in F5 was also found to be associated with ACEI-AE or ARB-AE, P = 2.09 \u00d7 10-3 . A combined gene risk score of these variants, and the common variants rs6025 and rs6020, showed that individuals carrying at least one variant had 2.21 (95% CI, 1.49-3.27, P = 6.30 \u00d7 10-9 ) times the odds of having ACEI-AE or ARB-AE. The increased risk due to the common Leiden allele was confirmed in a genome-wide association study from the United States. A high risk of angioedema was also observed for the rs6020 variant that is the main coagulation defect-causing variant in black African and Asian populations. We found that deleterious missense variants in F5 are associated with an increased risk of ACEI-AE or ARB-AE.", "doi": "10.1002/cpt.1927", "pmid": "32496628", "labels": {"National Genomics Infrastructure": "Collaborative", "NGI Uppsala (SNP&SEQ Technology Platform)": "Collaborative"}, "xrefs": [], "notes": [], "created": "2020-11-16T09:14:47.719Z", "modified": "2021-11-10T12:44:38.679Z"}, {"entity": "publication", "iuid": "654029ff29274b27bc5f4a687bf8d376", "links": {"self": {"href": "https://publications.scilifelab.se/publication/654029ff29274b27bc5f4a687bf8d376.json"}, "display": {"href": "https://publications.scilifelab.se/publication/654029ff29274b27bc5f4a687bf8d376"}}, "title": "Esomeprazole reduces sperm motility index by targeting the spermic cholinergic machinery: A mechanistic study for the association between use of proton pump inhibitors and reduced sperm motility index.", "authors": [{"family": "Kumar", "given": "Amit", "initials": "A"}, {"family": "Kumar", "given": "Rajnish", "initials": "R"}, {"family": "Flanagan", "given": "John", "initials": "J"}, {"family": "L\u00e5ngstr\u00f6m", "given": "Bengt", "initials": "B"}, {"family": "Bj\u00f6rndahl", "given": "Lars", "initials": "L"}, {"family": "Darreh-Shori", "given": "Taher", "initials": "T"}], "type": "journal article", "published": "2020-12-00", "journal": {"title": "Biochem. Pharmacol.", "issn": "1873-2968", "volume": "182", "pages": "114212", "issn-l": "0006-2952"}, "abstract": "Recent studies have linked prolonged use of the most commonly prescribed proton pump inhibitors (PPIs) with declined human sperm function and infertility. Here, we report for the first time the most plausible underlying mechanism for this unwarranted secondary mode of action. We followed up on a recent serendipitous discovery in our laboratory regarding PPIs' off-target action and performed detailed pharmacodynamic analyses by combining in silico and in vitro studies to determine the off-target effect of one of the most commonly used PPI, esomeprazole, on the key human acetylcholine biosynthesizing enzyme, choline acetyltransferase (ChAT; EC 2.3.1.6). A pivotal enzyme in the spermic cholinergic system that governs the sperm motility, concentration and quality. Our results were conclusive and showed that both the racemic form, omeprazole and its pure S-enantiomer, esomeprazole, acted as potent mixed-competitive inhibitor of human ChAT with a global inhibition constant (Ki) of 88 nM (95%CI: 10-167 nM) for esomeprazole and 178 nM (95%CI: 140-230 nM) for the racemic drug omeprazole. Most importantly, esomeprazole substantially reduces both total number of motile sperm (by 36%, p < 0.001; and 21% p < 0.0001, at 10 and 100 nM, respectively) as well as the total number of sperm with progressive motility (by 42% p < 0.0016 and by 26% p < 0.0001, respectively) after 60 min relative to 20 min incubation in our ex vivo functional assay performed on ejaculated human sperm. In conclusion, this study presents a completely new perspective regarding PPIs secondary mode of action/unwarranted side effects and calls for further mechanistic and larger clinical studies to elucidate the role of PPIs in infertility.", "doi": "10.1016/j.bcp.2020.114212", "pmid": "32866455", "labels": {"Protein Science Facility (PSF)": "Service"}, "xrefs": [{"db": "pii", "key": "S0006-2952(20)30448-2"}], "notes": [], "created": "2024-04-03T14:17:50.894Z", "modified": "2024-04-03T14:17:50.899Z"}, {"entity": "publication", "iuid": "3c2e6b91baaf43ae9efca4b999d27a81", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3c2e6b91baaf43ae9efca4b999d27a81.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3c2e6b91baaf43ae9efca4b999d27a81"}}, "title": "Effect of RNA silencing suppression activity of chrysanthemum virus B p12 protein on small RNA species.", "authors": [{"family": "Vetukuri", "given": "Ramesh R", "initials": "RR"}, {"family": "Kalyandurg", "given": "Pruthvi B", "initials": "PB"}, {"family": "Saripella", "given": "Ganapathi Varma", "initials": "GV"}, {"family": "Sen", "given": "Diya", "initials": "D"}, {"family": "Gil", "given": "Jose Fernando", "initials": "JF"}, {"family": "Lukhovitskaya", "given": "Nina I", "initials": "NI"}, {"family": "Grenville-Briggs", "given": "Laura J", "initials": "LJ"}, {"family": "Savenkov", "given": "Eugene I", "initials": "EI", "orcid": "0000-0002-5802-5089", "researcher": {"href": "https://publications.scilifelab.se/researcher/5e4c252bb7ec444c935c0aae5387df53.json"}}], "type": "journal article", "published": "2020-12-00", "journal": {"title": "Arch Virol", "issn": "1432-8798", "volume": "165", "issue": "12", "pages": "2953-2959", "issn-l": null}, "abstract": "Chrysanthemum virus B encodes a multifunctional p12 protein that acts as a transcriptional activator in the nucleus and as a suppressor of RNA silencing in the cytoplasm. Here, we investigated the impact of p12 on accumulation of major classes of small RNAs (sRNAs). The results show dramatic changes in the sRNA profiles characterised by an overall reduction in sRNA accumulation, changes in the pattern of size distribution of canonical siRNAs and in the ratio between sense and antisense strands, lower abundance of siRNAs with a U residue at the 5'-terminus, and changes in the expression of certain miRNAs, most of which were downregulated.", "doi": "10.1007/s00705-020-04832-y", "pmid": "33040310", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1007/s00705-020-04832-y"}, {"db": "pmc", "key": "PMC7588395"}], "notes": [], "created": "2020-12-07T16:32:30.292Z", "modified": "2021-11-10T12:44:41.396Z"}, {"entity": "publication", "iuid": "7aff62d808ef404a8b5a402908f43327", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7aff62d808ef404a8b5a402908f43327.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7aff62d808ef404a8b5a402908f43327"}}, "title": "Dysregulation in Akt/mTOR/HIF-1 signaling identified by proteo-transcriptomics of SARS-CoV-2 infected cells.", "authors": [{"family": "Appelberg", "given": "Sofia", "initials": "S"}, {"family": "Gupta", "given": "Soham", "initials": "S"}, {"family": "Svensson Akusj\u00e4rvi", "given": "Sara", "initials": "S"}, {"family": "Ambikan", "given": "Anoop T", "initials": "AT"}, {"family": "Mikaeloff", "given": "Flora", "initials": "F"}, {"family": "Saccon", "given": "Elisa", "initials": "E"}, {"family": "V\u00e9gv\u00e1ri", "given": "\u00c1kos", "initials": "\u00c1"}, {"family": "Benfeitas", "given": "Rui", "initials": "R"}, {"family": "Sperk", "given": "Maike", "initials": "M"}, {"family": "St\u00e5hlberg", "given": "Marie", "initials": "M"}, {"family": "Krishnan", "given": "Shuba", "initials": "S"}, {"family": "Singh", "given": "Kamal", "initials": "K"}, {"family": "Penninger", "given": "Josef M", "initials": "JM"}, {"family": "Mirazimi", "given": "Ali", "initials": "A"}, {"family": "Neogi", "given": "Ujjwal", "initials": "U", "orcid": "0000-0002-0844-3338", "researcher": {"href": "https://publications.scilifelab.se/researcher/2f8094017c2a4d0a94d72813cab526f7.json"}}], "type": "journal article", "published": "2020-12-00", "journal": {"title": "Emerg Microbes Infect", "issn": "2222-1751", "volume": "9", "issue": "1", "pages": "1748-1760", "issn-l": "2222-1751"}, "abstract": "How severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections engage cellular host pathways and innate immunity in infected cells remains largely elusive. We performed an integrative proteo-transcriptomics analysis in SARS-CoV-2 infected Huh7 cells to map the cellular response to the invading virus over time. We identified four pathways, ErbB, HIF-1, mTOR and TNF signaling, among others that were markedly modulated during the course of the SARS-CoV-2 infection in vitro. Western blot validation of the downstream effector molecules of these pathways revealed a dose-dependent activation of Akt, mTOR, S6K1 and 4E-BP1 at 24 hours post infection (hpi). However, we found a significant inhibition of HIF-1\u03b1 through 24hpi and 48hpi of the infection, suggesting a crosstalk between the SARS-CoV-2 and the Akt/mTOR/HIF-1 signaling pathways. Inhibition of the mTOR signaling pathway using Akt inhibitor MK-2206 showed a significant reduction in virus production. Further investigations are required to better understand the molecular sequelae in order to guide potential therapy in the management of severe coronavirus disease 2019 (COVID-19) patients.", "doi": "10.1080/22221751.2020.1799723", "pmid": "32691695", "labels": {"Bioinformatics Support and Infrastructure": "Service", "Bioinformatics Support, Infrastructure and Training": "Service", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7473213"}], "notes": [], "created": "2020-09-24T09:28:47.205Z", "modified": "2024-01-16T13:48:41.261Z"}, {"entity": "publication", "iuid": "ee2e40bee1cc4d14944c57aac8d0f1c9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ee2e40bee1cc4d14944c57aac8d0f1c9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ee2e40bee1cc4d14944c57aac8d0f1c9"}}, "title": "Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals.", "authors": [{"family": "Surendran", "given": "Praveen", "initials": "P"}, {"family": "Feofanova", "given": "Elena V", "initials": "EV", "orcid": "0000-0003-1428-7199", "researcher": {"href": "https://publications.scilifelab.se/researcher/1045cc4a1b224b40bc61748fb55836c9.json"}}, {"family": "Lahrouchi", "given": "Najim", "initials": "N"}, {"family": "Ntalla", "given": "Ioanna", "initials": "I"}, {"family": "Karthikeyan", "given": "Savita", "initials": "S"}, {"family": "Cook", "given": "James", "initials": "J"}, {"family": "Chen", "given": "Lingyan", "initials": "L"}, {"family": "Mifsud", "given": "Borbala", "initials": "B"}, {"family": "Yao", "given": "Chen", "initials": "C"}, {"family": "Kraja", "given": "Aldi T", "initials": "AT"}, {"family": "Cartwright", "given": "James H", "initials": "JH"}, {"family": "Hellwege", "given": "Jacklyn N", "initials": "JN"}, {"family": "Giri", "given": "Ayush", "initials": "A"}, {"family": "Tragante", "given": "Vinicius", "initials": "V"}, {"family": "Thorleifsson", "given": "Gudmar", "initials": "G"}, {"family": "Liu", "given": "Dajiang J", "initials": "DJ"}, {"family": "Prins", "given": "Bram P", "initials": "BP"}, {"family": "Stewart", "given": "Isobel D", "initials": "ID"}, {"family": "Cabrera", "given": "Claudia P", "initials": "CP"}, {"family": "Eales", "given": "James M", "initials": "JM"}, {"family": "Akbarov", "given": "Artur", "initials": "A"}, {"family": "Auer", "given": "Paul L", "initials": "PL"}, {"family": "Bielak", "given": "Lawrence F", "initials": "LF"}, {"family": "Bis", "given": "Joshua C", "initials": "JC"}, {"family": "Braithwaite", "given": "Vickie S", "initials": "VS"}, {"family": "Brody", "given": "Jennifer A", "initials": "JA"}, {"family": "Daw", "given": "E Warwick", "initials": "EW"}, {"family": "Warren", "given": "Helen R", "initials": "HR"}, {"family": "Drenos", "given": "Fotios", "initials": "F"}, {"family": "Nielsen", "given": "Sune Fallgaard", "initials": "SF"}, {"family": "Faul", "given": "Jessica D", "initials": "JD"}, {"family": "Fauman", "given": "Eric B", "initials": "EB"}, {"family": "Fava", "given": "Cristiano", "initials": "C"}, {"family": "Ferreira", "given": "Teresa", "initials": "T"}, {"family": "Foley", "given": "Christopher N", "initials": "CN"}, {"family": "Franceschini", "given": "Nora", "initials": "N"}, {"family": "Gao", "given": "He", "initials": "H"}, {"family": "Giannakopoulou", "given": "Olga", "initials": "O"}, {"family": "Giulianini", "given": "Franco", "initials": "F"}, {"family": "Gudbjartsson", "given": "Daniel F", "initials": "DF"}, {"family": "Guo", "given": "Xiuqing", "initials": "X"}, {"family": "Harris", "given": "Sarah E", "initials": "SE"}, {"family": "Havulinna", "given": "Aki S", "initials": "AS"}, {"family": "Helgadottir", "given": "Anna", "initials": "A"}, {"family": "Huffman", "given": "Jennifer E", "initials": "JE"}, {"family": "Hwang", "given": "Shih-Jen", "initials": "S"}, {"family": "Kanoni", "given": "Stavroula", "initials": "S"}, {"family": "Kontto", "given": "Jukka", "initials": "J"}, {"family": "Larson", "given": "Martin G", "initials": "MG"}, {"family": "Li-Gao", "given": "Ruifang", "initials": "R"}, {"family": "Lindstr\u00f6m", "given": "Jaana", "initials": "J"}, {"family": "Lotta", "given": "Luca A", "initials": "LA"}, {"family": "Lu", "given": "Yingchang", "initials": "Y"}, {"family": "Luan", "given": "Jian'an", "initials": "J"}, {"family": "Mahajan", "given": "Anubha", "initials": "A"}, {"family": "Malerba", "given": "Giovanni", "initials": "G"}, {"family": "Masca", "given": "Nicholas G D", "initials": "NGD"}, {"family": "Mei", "given": "Hao", "initials": "H"}, {"family": "Menni", "given": "Cristina", "initials": "C"}, {"family": "Mook-Kanamori", "given": "Dennis O", "initials": "DO"}, {"family": "Mosen-Ansorena", "given": "David", "initials": "D"}, {"family": "M\u00fcller-Nurasyid", "given": "Martina", "initials": "M"}, {"family": "Par\u00e9", "given": "Guillaume", "initials": "G"}, {"family": "Paul", "given": "Dirk S", "initials": "DS"}, {"family": "Perola", "given": "Markus", "initials": "M"}, {"family": "Poveda", "given": "Alaitz", "initials": "A"}, {"family": "Rauramaa", "given": "Rainer", "initials": "R"}, {"family": "Richard", "given": "Melissa", "initials": "M"}, {"family": "Richardson", "given": "Tom G", "initials": "TG"}, {"family": "Sep\u00falveda", "given": "Nuno", "initials": "N"}, {"family": "Sim", "given": "Xueling", "initials": "X"}, {"family": "Smith", "given": "Albert V", "initials": "AV"}, {"family": "Smith", "given": "Jennifer A", "initials": "JA"}, {"family": "Staley", "given": "James R", "initials": "JR"}, {"family": "Stan\u00e1kov\u00e1", "given": "Alena", "initials": "A"}, {"family": "Sulem", "given": "Patrick", "initials": "P"}, {"family": "Th\u00e9riault", "given": "S\u00e9bastien", "initials": "S"}, {"family": "Thorsteinsdottir", "given": "Unnur", "initials": "U"}, {"family": "Trompet", "given": "Stella", "initials": "S"}, {"family": "Varga", "given": "Tibor V", "initials": "TV"}, {"family": "Velez Edwards", "given": "Digna R", "initials": "DR"}, {"family": "Veronesi", "given": "Giovanni", "initials": "G"}, {"family": "Weiss", "given": "Stefan", "initials": "S"}, {"family": "Willems", "given": "Sara M", "initials": "SM"}, {"family": "Yao", "given": "Jie", "initials": "J"}, {"family": "Young", "given": "Robin", "initials": "R"}, {"family": "Yu", "given": "Bing", "initials": "B"}, {"family": "Zhang", "given": "Weihua", "initials": "W"}, {"family": "Zhao", "given": "Jing-Hua", "initials": "J"}, {"family": "Zhao", "given": "Wei", "initials": "W"}, {"family": "Evangelou", "given": "Evangelos", "initials": "E"}, {"family": "Aeschbacher", "given": "Stefanie", "initials": "S"}, {"family": "Asllanaj", "given": "Eralda", "initials": "E"}, {"family": "Blankenberg", "given": "Stefan", "initials": "S"}, {"family": "Bonnycastle", "given": "Lori L", "initials": "LL"}, {"family": "Bork-Jensen", "given": "Jette", "initials": "J"}, {"family": "Brandslund", "given": "Ivan", "initials": "I"}, {"family": "Braund", "given": "Peter S", "initials": "PS"}, {"family": "Burgess", "given": "Stephen", "initials": "S"}, {"family": "Cho", "given": "Kelly", "initials": "K"}, {"family": "Christensen", "given": "Cramer", "initials": "C"}, {"family": "Connell", "given": "John", "initials": "J"}, {"family": "Mutsert", "given": "Ren\u00e9e de", "initials": "Rd"}, {"family": "Dominiczak", "given": "Anna F", "initials": "AF"}, {"family": "D\u00f6rr", "given": "Marcus", "initials": "M"}, {"family": "Eiriksdottir", "given": "Gudny", "initials": "G"}, {"family": "Farmaki", "given": "Aliki-Eleni", "initials": "A"}, {"family": "Gaziano", "given": "J Michael", "initials": "JM"}, {"family": "Grarup", "given": "Niels", "initials": "N"}, {"family": "Grove", "given": "Megan L", "initials": "ML"}, {"family": "Hallmans", "given": "G\u00f6ran", "initials": "G"}, {"family": "Hansen", "given": "Torben", "initials": "T"}, {"family": "Have", "given": "Christian T", "initials": "CT"}, {"family": "Heiss", "given": "Gerardo", "initials": "G"}, {"family": "J\u00f8rgensen", "given": "Marit E", "initials": "ME"}, {"family": "Jousilahti", "given": "Pekka", "initials": "P"}, {"family": "Kajantie", "given": "Eero", "initials": "E"}, {"family": "Kamat", "given": "Mihir", "initials": "M"}, {"family": "K\u00e4r\u00e4j\u00e4m\u00e4ki", "given": "AnneMari", "initials": "A"}, {"family": "Karpe", "given": "Fredrik", "initials": "F"}, {"family": "Koistinen", "given": "Heikki A", "initials": "HA"}, {"family": "Kovesdy", "given": "Csaba P", "initials": "CP"}, {"family": "Kuulasmaa", "given": "Kari", "initials": "K"}, {"family": "Laatikainen", "given": "Tiina", "initials": "T"}, {"family": "Lannfelt", "given": "Lars", "initials": "L"}, {"family": "Lee", "given": "I-Te", "initials": "I"}, {"family": "Lee", "given": "Wen-Jane", "initials": "W"}, {"family": "LifeLines Cohort Study", "given": "", "initials": ""}, {"family": "Linneberg", "given": "Allan", "initials": "A"}, {"family": "Martin", "given": "Lisa W", "initials": "LW"}, {"family": "Moitry", "given": "Marie", "initials": "M"}, {"family": "Nadkarni", "given": "Girish", "initials": "G"}, {"family": "Neville", "given": "Matt J", "initials": "MJ"}, {"family": "Palmer", "given": "Colin N A", "initials": "CNA"}, {"family": "Papanicolaou", "given": "George J", "initials": "GJ"}, {"family": "Pedersen", "given": "Oluf", "initials": "O"}, {"family": "Peters", "given": "James", "initials": "J"}, {"family": "Poulter", "given": "Neil", "initials": "N"}, {"family": "Rasheed", "given": "Asif", "initials": "A"}, {"family": "Rasmussen", "given": "Katrine L", "initials": "KL"}, {"family": "Rayner", "given": "N William", "initials": "NW"}, {"family": "M\u00e4gi", "given": "Reedik", "initials": "R"}, {"family": "Renstr\u00f6m", "given": "Frida", "initials": "F"}, {"family": "Rettig", "given": "Rainer", "initials": "R"}, {"family": "Rossouw", "given": "Jacques", "initials": "J"}, {"family": "Schreiner", "given": "Pamela J", "initials": "PJ"}, {"family": "Sever", "given": "Peter S", "initials": "PS"}, {"family": "Sigurdsson", "given": "Emil L", "initials": "EL"}, {"family": "Skaaby", "given": "Tea", "initials": "T"}, {"family": "Sun", "given": "Yan V", "initials": "YV"}, {"family": "Sundstrom", "given": "Johan", "initials": "J"}, {"family": "Thorgeirsson", "given": "Gudmundur", "initials": "G"}, {"family": "Esko", "given": "T\u00f5nu", "initials": "T"}, {"family": "Trabetti", "given": "Elisabetta", "initials": "E"}, {"family": "Tsao", "given": "Philip S", "initials": "PS"}, {"family": "Tuomi", "given": "Tiinamaija", "initials": "T"}, {"family": "Turner", "given": "Stephen T", "initials": "ST"}, {"family": "Tzoulaki", "given": "Ioanna", "initials": "I"}, {"family": "Vaartjes", "given": "Ilonca", "initials": "I"}, {"family": "Vergnaud", "given": "Anne-Claire", "initials": "A"}, {"family": "Willer", "given": "Cristen J", "initials": "CJ"}, {"family": "Wilson", "given": "Peter W F", "initials": "PWF"}, {"family": "Witte", "given": "Daniel R", "initials": "DR"}, {"family": "Yonova-Doing", "given": "Ekaterina", "initials": "E"}, {"family": "Zhang", "given": "He", "initials": "H"}, {"family": "Aliya", "given": "Naheed", "initials": "N"}, {"family": "Almgren", "given": "Peter", "initials": "P"}, {"family": "Amouyel", "given": "Philippe", "initials": "P"}, {"family": "Asselbergs", "given": "Folkert W", "initials": "FW"}, {"family": "Barnes", "given": "Michael R", "initials": "MR"}, {"family": "Blakemore", "given": "Alexandra I", "initials": "AI"}, {"family": "Boehnke", "given": "Michael", "initials": "M"}, {"family": "Bots", "given": "Michiel L", "initials": "ML"}, {"family": "Bottinger", "given": "Erwin P", "initials": "EP"}, {"family": "Buring", "given": "Julie E", "initials": "JE"}, {"family": "Chambers", "given": "John C", "initials": "JC"}, {"family": "Chen", "given": "Yii-Der Ida", "initials": "YI"}, {"family": "Chowdhury", "given": "Rajiv", "initials": "R"}, {"family": "Conen", "given": "David", "initials": "D"}, {"family": "Correa", "given": "Adolfo", "initials": "A"}, {"family": "Davey Smith", "given": "George", "initials": "G"}, {"family": "Boer", "given": "Rudolf A de", "initials": "RAd"}, {"family": "Deary", "given": "Ian J", "initials": "IJ"}, {"family": "Dedoussis", "given": "George", "initials": "G"}, {"family": "Deloukas", "given": "Panos", "initials": "P"}, {"family": "Di Angelantonio", "given": "Emanuele", "initials": "E"}, {"family": "Elliott", "given": "Paul", "initials": "P"}, {"family": "EPIC-CVD", "given": "", "initials": ""}, {"family": "EPIC-InterAct", "given": "", "initials": ""}, {"family": "Felix", "given": "Stephan B", "initials": "SB"}, {"family": "Ferri\u00e8res", "given": "Jean", "initials": "J"}, {"family": "Ford", "given": "Ian", "initials": "I"}, {"family": "Fornage", "given": "Myriam", "initials": "M"}, {"family": "Franks", "given": "Paul W", "initials": "PW"}, {"family": "Franks", "given": "Stephen", "initials": "S"}, {"family": "Frossard", "given": "Philippe", "initials": "P"}, {"family": "Gambaro", "given": "Giovanni", "initials": "G"}, {"family": "Gaunt", "given": "Tom R", "initials": "TR"}, {"family": "Groop", "given": "Leif", "initials": "L"}, {"family": "Gudnason", "given": "Vilmundur", "initials": "V"}, {"family": "Harris", "given": "Tamara B", "initials": "TB"}, {"family": "Hayward", "given": "Caroline", "initials": "C"}, {"family": "Hennig", "given": "Branwen J", "initials": "BJ"}, {"family": "Herzig", "given": "Karl-Heinz", "initials": "K"}, {"family": "Ingelsson", "given": "Erik", "initials": "E"}, {"family": "Tuomilehto", "given": "Jaakko", "initials": "J"}, {"family": "J\u00e4rvelin", "given": "Marjo-Riitta", "initials": "M"}, {"family": "Jukema", "given": "J Wouter", "initials": "JW"}, {"family": "Kardia", "given": "Sharon L R", "initials": "SLR"}, {"family": "Kee", "given": "Frank", "initials": "F"}, {"family": "Kooner", "given": "Jaspal S", "initials": "JS"}, {"family": "Kooperberg", "given": "Charles", "initials": "C"}, {"family": "Launer", "given": "Lenore J", "initials": "LJ"}, {"family": "Lind", "given": "Lars", "initials": "L"}, {"family": "Loos", "given": "Ruth J F", "initials": "RJF"}, {"family": "Majumder", "given": "Abdulla Al Shafi", "initials": "AAS"}, {"family": "Laakso", "given": "Markku", "initials": "M"}, {"family": "McCarthy", "given": "Mark I", "initials": "MI"}, {"family": "Melander", "given": "Olle", "initials": "O"}, {"family": "Mohlke", "given": "Karen L", "initials": "KL"}, {"family": "Murray", "given": "Alison D", "initials": "AD"}, {"family": "Nordestgaard", "given": "B\u00f8rge Gr\u00f8nne", "initials": "BG"}, {"family": "Orho-Melander", "given": "Marju", "initials": "M"}, {"family": "Packard", "given": "Chris J", "initials": "CJ"}, {"family": "Padmanabhan", "given": "Sandosh", "initials": "S"}, {"family": "Palmas", "given": "Walter", "initials": "W"}, {"family": "Polasek", "given": "Ozren", "initials": "O"}, {"family": "Porteous", "given": "David J", "initials": "DJ"}, {"family": "Prentice", "given": "Andrew M", "initials": "AM"}, {"family": "Province", "given": "Michael A", "initials": "MA"}, {"family": "Relton", "given": "Caroline L", "initials": "CL"}, {"family": "Rice", "given": "Kenneth", "initials": "K"}, {"family": "Ridker", "given": "Paul M", "initials": "PM"}, {"family": "Rolandsson", "given": "Olov", "initials": "O"}, {"family": "Rosendaal", "given": "Frits R", "initials": "FR"}, {"family": "Rotter", "given": "Jerome I", "initials": "JI"}, {"family": "Rudan", "given": "Igor", "initials": "I"}, {"family": "Salomaa", "given": "Veikko", "initials": "V"}, {"family": "Samani", "given": "Nilesh J", "initials": "NJ"}, {"family": "Sattar", "given": "Naveed", "initials": "N"}, {"family": "Sheu", "given": "Wayne H-H", "initials": "WH"}, {"family": "Smith", "given": "Blair H", "initials": "BH"}, {"family": "Soranzo", "given": "Nicole", "initials": "N"}, {"family": "Spector", "given": "Timothy D", "initials": "TD"}, {"family": "Starr", "given": "John M", "initials": "JM"}, {"family": "Sebert", "given": "Sylvain", "initials": "S"}, {"family": "Taylor", "given": "Kent D", "initials": "KD"}, {"family": "Lakka", "given": "Timo A", "initials": "TA"}, {"family": "Timpson", "given": "Nicholas J", "initials": "NJ"}, {"family": "Tobin", "given": "Martin D", "initials": "MD"}, {"family": "Understanding Society Scientific Group", "given": "", "initials": ""}, {"family": "van der Harst", "given": "Pim", "initials": "P"}, {"family": "van der Meer", "given": "Peter", "initials": "P"}, {"family": "Ramachandran", "given": "Vasan S", "initials": "VS"}, {"family": "Verweij", "given": "Niek", "initials": "N"}, {"family": "Virtamo", "given": "Jarmo", "initials": "J"}, {"family": "V\u00f6lker", "given": "Uwe", "initials": "U"}, {"family": "Weir", "given": "David R", "initials": "DR"}, {"family": "Zeggini", "given": "Eleftheria", "initials": "E"}, {"family": "Charchar", "given": "Fadi J", "initials": "FJ"}, {"family": "Million Veteran Program", "given": "", "initials": ""}, {"family": "Wareham", "given": "Nicholas J", "initials": "NJ"}, {"family": "Langenberg", "given": "Claudia", "initials": "C"}, {"family": "Tomaszewski", "given": "Maciej", "initials": "M"}, {"family": "Butterworth", "given": "Adam S", "initials": "AS"}, {"family": "Caulfield", "given": "Mark J", "initials": "MJ"}, {"family": "Danesh", "given": "John", "initials": "J"}, {"family": "Edwards", "given": "Todd L", "initials": "TL"}, {"family": "Holm", "given": "Hilma", "initials": "H"}, {"family": "Hung", "given": "Adriana M", "initials": "AM"}, {"family": "Lindgren", "given": "Cecilia M", "initials": "CM"}, {"family": "Liu", "given": "Chunyu", "initials": "C"}, {"family": "Manning", "given": "Alisa K", "initials": "AK"}, {"family": "Morris", "given": "Andrew P", "initials": "AP"}, {"family": "Morrison", "given": "Alanna C", "initials": "AC"}, {"family": "O'Donnell", "given": "Christopher J", "initials": "CJ"}, {"family": "Psaty", "given": "Bruce M", "initials": "BM"}, {"family": "Saleheen", "given": "Danish", "initials": "D"}, {"family": "Stefansson", "given": "Kari", "initials": "K"}, {"family": "Boerwinkle", "given": "Eric", "initials": "E"}, {"family": "Chasman", "given": "Daniel I", "initials": "DI", "orcid": "0000-0003-3357-0862", "researcher": {"href": "https://publications.scilifelab.se/researcher/1c06690291064fe58836958edbcaafbc.json"}}, {"family": "Levy", "given": "Daniel", "initials": "D"}, {"family": "Newton-Cheh", "given": "Christopher", "initials": "C"}, {"family": "Munroe", "given": "Patricia B", "initials": "PB", "orcid": "0000-0002-4176-2947", "researcher": {"href": "https://publications.scilifelab.se/researcher/657544a7f921459f926aae5cd0e2065c.json"}}, {"family": "Howson", "given": "Joanna M M", "initials": "JMM", "orcid": "0000-0001-7618-0050", "researcher": {"href": "https://publications.scilifelab.se/researcher/d427fc29d217410fa1d84c0f9e2bf015.json"}}], "type": "journal article", "published": "2020-12-00", "journal": {"title": "Nat. Genet.", "issn": "1546-1718", "issn-l": "1061-4036", "volume": "52", "issue": "12", "pages": "1314-1332"}, "abstract": "Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.3 million participants, we discovered 106 new BP-associated genomic regions and 87 rare (minor allele frequency \u2264 0.01) variant BP associations (P < 5 \u00d7 10-8), of which 32 were in new BP-associated loci and 55 were independent BP-associated single-nucleotide variants within known BP-associated regions. Average effects of rare variants (44% coding) were ~8 times larger than common variant effects and indicate potential candidate causal genes at new and known loci (for example, GATA5 and PLCB3). BP-associated variants (including rare and common) were enriched in regions of active chromatin in fetal tissues, potentially linking fetal development with BP regulation in later life. Multivariable Mendelian randomization suggested possible inverse effects of elevated systolic and diastolic BP on large artery stroke. Our study demonstrates the utility of rare-variant analyses for identifying candidate genes and the results highlight potential therapeutic targets.", "doi": "10.1038/s41588-020-00713-x", "pmid": "33230300", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41588-020-00713-x"}, {"db": "pmc", "key": "PMC7610439"}, {"db": "mid", "key": "EMS118016"}], "notes": [], "created": "2021-01-07T17:01:50.081Z", "modified": "2021-12-07T13:35:55.172Z"}, {"entity": "publication", "iuid": "1c0901dfe7fb4a8cbf9f328f0845f6b2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1c0901dfe7fb4a8cbf9f328f0845f6b2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1c0901dfe7fb4a8cbf9f328f0845f6b2"}}, "title": "Differentiation of two Maytenus species and their hybrid via untargeted metabolomics", "authors": [{"family": "Antunes", "given": "Elisa Ribeiro Miranda", "initials": "ERM"}, {"family": "Duarte", "given": "Rodolfo Santos", "initials": "RS"}, {"family": "Moritz", "given": "Thomas", "initials": "T", "orcid": "0000-0002-4258-3190", "researcher": {"href": "https://publications.scilifelab.se/researcher/95ad5b7fe48f42eda1328f54a385e097.json"}}, {"family": "Sawaya", "given": "Alexandra Christine Helena Frankland", "initials": "ACHF"}], "type": "journal-article", "published": "2020-12-00", "journal": {"title": "Industrial Crops and Products", "issn": "0926-6690", "volume": "158", "issue": null, "pages": "113014", "issn-l": null}, "abstract": null, "doi": "10.1016/j.indcrop.2020.113014", "pmid": null, "labels": {"Swedish Metabolomics Centre": "Service"}, "xrefs": [], "notes": [], "created": "2020-12-11T12:03:37.873Z", "modified": "2025-10-17T13:03:16.530Z"}, {"entity": "publication", "iuid": "673a6b733f014264bc7e01ea2db87556", "links": {"self": {"href": "https://publications.scilifelab.se/publication/673a6b733f014264bc7e01ea2db87556.json"}, "display": {"href": "https://publications.scilifelab.se/publication/673a6b733f014264bc7e01ea2db87556"}}, "title": "Deep sequencing detects human papillomavirus (HPV) in cervical cancers negative for HPV by PCR.", "authors": [{"family": "Arroyo M\u00fchr", "given": "Laila Sara", "initials": "LS", "orcid": "0000-0003-2498-5206", "researcher": {"href": "https://publications.scilifelab.se/researcher/f0df178b81f149f48f3533bae976c511.json"}}, {"family": "Lagheden", "given": "Camilla", "initials": "C"}, {"family": "Lei", "given": "Jiayao", "initials": "J", "orcid": "0000-0002-4718-1414", "researcher": {"href": "https://publications.scilifelab.se/researcher/ea2b0586a048449880a0843ef29a04c0.json"}}, {"family": "Eklund", "given": "Carina", "initials": "C"}, {"family": "Nordqvist Kleppe", "given": "Sara", "initials": "S"}, {"family": "Spar\u00e9n", "given": "P\u00e4r", "initials": "P", "orcid": "0000-0002-5184-8971", "researcher": {"href": "https://publications.scilifelab.se/researcher/48e73c79f3a24128b82c5a71616e3659.json"}}, {"family": "Sundstr\u00f6m", "given": "Karin", "initials": "K", "orcid": "0000-0002-6865-0224", "researcher": {"href": "https://publications.scilifelab.se/researcher/d037c005ee2c431fae353340f5589e20.json"}}, {"family": "Dillner", "given": "Joakim", "initials": "J", "orcid": "0000-0001-8588-6506", "researcher": {"href": "https://publications.scilifelab.se/researcher/2b5c258635ad412f9e79994dcee4e323.json"}}], "type": "journal article", "published": "2020-12-00", "journal": {"title": "Br. J. Cancer", "issn": "1532-1827", "volume": "123", "issue": "12", "pages": "1790-1795", "issn-l": "0007-0920"}, "abstract": "Human papillomavirus (HPV) is a necessary cause of cervical cancer, although some invasive cervical cancers may test negative by HPV PCR. We previously requested all invasive cervical cancers in Sweden during 10 years and subjected them to PCR. We also optimised methods for deep sequencing of formalin-fixed paraffin-embedded samples.\n\nUsing Novaseq 6000, we simultaneously sequenced total DNA and cDNA from 392 HPV PCR-negative cervical cancers. Non-human reads were queried against all known HPVs. The complete database now contains PCR and/or deep sequencing data on 2850 invasive cervical cancers.\n\nHPV sequences were detected in 169/392 of HPV PCR-negative cervical cancers. Overall, 30 different HPV types were detected, but only 5 types were present in proportions above 3% of cancers. More than 92% of tumours were HPV-positive in PCR and/or sequencing (95% confidence interval: 91.1-93.1%). Exploring possible reasons for failure to previously detect HPV suggest that more sensitive type-specific PCRs for HPV 31, 33, 45 and 73 targeting retained regions of HPV would have detected most of these (117/392).\n\nUnbiased deep sequencing provides comprehensive data on HPV types in cervical cancers and appears to be an important tool for quality assurance of HPV screening.", "doi": "10.1038/s41416-020-01111-0", "pmid": "33020595", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41416-020-01111-0"}, {"db": "pmc", "key": "PMC7722749"}], "notes": [], "created": "2020-12-07T16:29:00.388Z", "modified": "2021-11-10T12:46:34.772Z"}, {"entity": "publication", "iuid": "9ff6ebcf5ec64cb5b5105569a6cd39e6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9ff6ebcf5ec64cb5b5105569a6cd39e6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9ff6ebcf5ec64cb5b5105569a6cd39e6"}}, "title": "Changes in lipid and carotenoid metabolism in Chlamydomonas reinhardtii during induction of CO2-concentrating mechanism: Cellular response to low CO2 stress", "authors": [{"family": "Abreu", "given": "Ilka N", "initials": "IN"}, {"family": "Aksmann", "given": "Anna", "initials": "A"}, {"family": "Bajhaiya", "given": "Amit K", "initials": "AK"}, {"family": "Benlloch", "given": "Reyes", "initials": "R"}, {"family": "Giordano", "given": "Mario", "initials": "M"}, {"family": "Pokora", "given": "Wojciech", "initials": "W"}, {"family": "Selstam", "given": "Eva", "initials": "E"}, {"family": "Moritz", "given": "Thomas", "initials": "T", "orcid": "0000-0002-4258-3190", "researcher": {"href": "https://publications.scilifelab.se/researcher/95ad5b7fe48f42eda1328f54a385e097.json"}}], "type": "journal-article", "published": "2020-12-00", "journal": {"title": "Algal Research", "issn": "2211-9264", "volume": "52", "issue": null, "pages": "102099", "issn-l": "2211-9264"}, "abstract": null, "doi": "10.1016/j.algal.2020.102099", "pmid": null, "labels": {"Swedish Metabolomics Centre": null}, "xrefs": [], "notes": [], "created": "2020-12-11T11:56:04.289Z", "modified": "2025-10-17T13:03:16.563Z"}, {"entity": "publication", "iuid": "e140ecab745546bc8925e35f5214d86e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e140ecab745546bc8925e35f5214d86e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e140ecab745546bc8925e35f5214d86e"}}, "title": "CRISPR and Long-Read Sequencing: A Perfect Match.", "authors": [{"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}], "type": "journal article", "published": "2020-12-00", "journal": {"title": "CRISPR J", "issn": "2573-1602", "volume": "3", "issue": "6", "pages": "425-427", "issn-l": null}, "abstract": null, "doi": "10.1089/crispr.2020.29110.aam", "pmid": "33252245", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Technology development", "National Genomics Infrastructure": "Technology development"}, "xrefs": [], "notes": [], "created": "2020-12-03T21:44:11.296Z", "modified": "2021-11-10T12:44:45.221Z"}, {"entity": "publication", "iuid": "ebfa912439df4a8d8ca9659fde4a8517", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ebfa912439df4a8d8ca9659fde4a8517.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ebfa912439df4a8d8ca9659fde4a8517"}}, "title": "Associations between serum concentrations of perfluoroalkyl substances and DNA methylation in women exposed through drinking water: A pilot study in Ronneby, Sweden.", "authors": [{"family": "Xu", "given": "Yiyi", "initials": "Y"}, {"family": "Jurkovic-Mlakar", "given": "Simona", "initials": "S"}, {"family": "Lindh", "given": "Christian H", "initials": "CH"}, {"family": "Scott", "given": "Kristin", "initials": "K"}, {"family": "Fletcher", "given": "Tony", "initials": "T"}, {"family": "Jakobsson", "given": "Kristina", "initials": "K"}, {"family": "Engstr\u00f6m", "given": "Karin", "initials": "K"}], "type": "journal article", "published": "2020-12-00", "journal": {"title": "Environ Int", "issn": "1873-6750", "volume": "145", "pages": "106148", "issn-l": "0160-4120"}, "abstract": "Perfluoroalkyl substances (PFAS) are widespread synthetic substances with various adverse health effects. A potential mechanism of toxicity for PFAS is via epigenetic changes, such as DNA methylation. However, few studies have evaluated associations between PFAS exposure and DNA methylation among adults, and data is especially scarce for women. Furthermore, exposure to environmental pollutants has been associated with epigenetic age acceleration, but no studies have yet evaluated whether PFAS is associated with epigenetic age acceleration.\n\nTo investigate whether exposure to PFAS is associated with alteration of DNA methylation and epigenetic age acceleration among women.\n\nIn this observational pilot study, 59 women (aged 20-47 years at enrollment in 2014) from Ronneby, Sweden, an area with historically high PFAS exposure due to local drinking water contamination, were divided into three PFAS exposure groups (low, medium, and high). Genome-wide methylation of whole-blood DNA was analyzed using the Infinium MethylationEPIC BeadChip. Ingenuity Pathway Analysis was used for in silico functional assessment. Epigenetic age acceleration was derived from the DNA methylation data using Horvath's epigenetic skin and blood clock.\n\n117 differentially methylated positions (q < 0.017) and one near-significantly differentially methylated region (S100A13, FWER = 0.020) were identified. In silico functional analyses suggested that genes with altered DNA methylation (q < 0.05) were annotated to cancer, endocrine system disorders, reproductive system disease, as well as pathways such as estrogen receptor signaling, cardiac hypertrophy signaling, PPAR\u03b1/RXR\u03b1 activation and telomerase signaling. No differences in epigenetic age acceleration between PFAS exposure groups were noted (p = 0.43).\n\nThe data suggests that PFAS exposure alters DNA methylation in women highly exposed to PFAS from drinking water. The observed associations should be verified in larger cohorts, and it should also be further investigated whether these changes in methylation also underlie potential phenotypic changes and/or adverse health effects of PFAS.", "doi": "10.1016/j.envint.2020.106148", "pmid": "33007577", "labels": {"Clinical Genomics Lund": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "S0160-4120(20)32103-6"}], "notes": [], "created": "2021-11-23T13:54:56.836Z", "modified": "2021-11-23T13:54:56.842Z"}, {"entity": "publication", "iuid": "f7aa6c1e8f454320b6257a67e8196a08", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f7aa6c1e8f454320b6257a67e8196a08.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f7aa6c1e8f454320b6257a67e8196a08"}}, "title": "A metabolite roadmap of the wood-forming tissue in Populus tremula.", "authors": [{"family": "Abreu", "given": "Ilka N", "initials": "IN", "orcid": "0000-0003-4728-0161", "researcher": {"href": "https://publications.scilifelab.se/researcher/1cb725d57dfe40588d386dafe2c58479.json"}}, {"family": "Johansson", "given": "Annika I", "initials": "AI", "orcid": "0000-0001-5000-1288", "researcher": {"href": "https://publications.scilifelab.se/researcher/0b0835b94db946929c1cb0c8f9319068.json"}}, {"family": "Soko\u0142owska", "given": "Katarzyna", "initials": "K", "orcid": "0000-0002-5874-207X", "researcher": {"href": "https://publications.scilifelab.se/researcher/13bfc250ddff4dc3a38073d0717f2a45.json"}}, {"family": "Niittyl\u00e4", "given": "Totte", "initials": "T", "orcid": "0000-0001-8029-1503", "researcher": {"href": "https://publications.scilifelab.se/researcher/f2b8823dc6cf44eaa309fcf157b1f28a.json"}}, {"family": "Sundberg", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Hvidsten", "given": "Torgeir R", "initials": "TR", "orcid": "0000-0001-6097-2539", "researcher": {"href": "https://publications.scilifelab.se/researcher/987fbb5763c74f6895bee64630528d8d.json"}}, {"family": "Street", "given": "Nathaniel R", "initials": "NR", "orcid": "0000-0001-6031-005X", "researcher": {"href": "https://publications.scilifelab.se/researcher/cb9ceb237a724046a1454179a32de1b0.json"}}, {"family": "Moritz", "given": "Thomas", "initials": "T", "orcid": "0000-0002-4258-3190", "researcher": {"href": "https://publications.scilifelab.se/researcher/95ad5b7fe48f42eda1328f54a385e097.json"}}], "type": "journal article", "published": "2020-12-00", "journal": {"title": "New Phytol.", "issn": "1469-8137", "volume": "228", "issue": "5", "pages": "1559-1572", "issn-l": "0028-646X"}, "abstract": "Wood, or secondary xylem, is the product of xylogenesis, a developmental process that begins with the proliferation of cambial derivatives and ends with mature xylem fibers and vessels with lignified secondary cell walls. Fully mature xylem has undergone a series of cellular processes, including cell division, cell expansion, secondary wall formation, lignification and programmed cell death. A complex network of interactions between transcriptional regulators and signal transduction pathways controls wood formation. However, the role of metabolites during this developmental process has not been comprehensively characterized. To evaluate the role of metabolites during wood formation, we performed a high spatial resolution metabolomics study of the wood-forming zone of Populus tremula, including laser dissected aspen ray and fiber cells. We show that metabolites show specific patterns within the wood-forming zone, following the differentiation process from cell division to cell death. The data from profiled laser dissected aspen ray and fiber cells suggests that these two cell types host distinctly different metabolic processes. Furthermore, by integrating previously published transcriptomic and proteomic profiles generated from the same trees, we provide an integrative picture of molecular processes, for example, deamination of phenylalanine during lignification is of critical importance for nitrogen metabolism during wood formation.", "doi": "10.1111/nph.16799", "pmid": "32648607", "labels": {"Bioinformatics Support for Computational Resources": "Service", "Swedish Metabolomics Centre": "Collaborative"}, "xrefs": [], "notes": [], "created": "2020-12-11T11:56:03.232Z", "modified": "2025-10-17T13:03:16.572Z"}, {"entity": "publication", "iuid": "8fbdb10cceb14b808433587b60f51045", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8fbdb10cceb14b808433587b60f51045.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8fbdb10cceb14b808433587b60f51045"}}, "title": "A genome-wide association study revealed five SNPs affecting 8-month weight in sheep.", "authors": [{"family": "Pasandideh", "given": "M", "initials": "M", "orcid": "0000-0001-5340-7072", "researcher": {"href": "https://publications.scilifelab.se/researcher/431b9c421917406c8d4f3769bfde17ed.json"}}, {"family": "Gholizadeh", "given": "M", "initials": "M"}, {"family": "Rahimi-Mianji", "given": "G", "initials": "G"}], "type": "journal article", "published": "2020-12-00", "journal": {"title": "Anim Genet", "issn": "1365-2052", "volume": "51", "issue": "6", "pages": "973-976", "issn-l": "0268-9146"}, "abstract": "Lamb weight at 8 months of age is an important trait in the sheep industry in terms of the onset of puberty around this age; however, knowledge of its effective genetic factors is limited. Therefore, a GWAS using the 50K SNP-Chip was performed on 96 Baluchi sheep to identify the genomic regions associated with 8-month weight. The results of the present study revealed five SNPs on chromosomes 4, 14 and 16 at 5% chromosome-wide significance level, jointly accounting for 0.95% of total genetic variance. Four genes - MTPN, HYDIN, LRGUK and ZFP90 - were found in 50 kb intervals around the significant SNPs, of which MTPN is involved in regulation of skeletal muscle growth. Our results may provide a new vision to identify the genomic regions affecting growth traits in sheep.", "doi": "10.1111/age.12996", "pmid": "32910467", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [], "notes": [], "created": "2020-10-20T06:59:17.372Z", "modified": "2021-11-10T12:44:54.023Z"}, {"entity": "publication", "iuid": "fab53bcfddc94028843f584f4820ef3c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/fab53bcfddc94028843f584f4820ef3c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/fab53bcfddc94028843f584f4820ef3c"}}, "title": "TrackMate: My favorite image analysis tool, by Neubias members", "authors": [{"family": "Klemm", "given": "Anna", "initials": "A", "orcid": "0000-0002-3466-1320", "researcher": {"href": "https://publications.scilifelab.se/researcher/4ae78afb2a424b0ab70d49871f361d13.json"}}], "type": null, "published": "2020-11-30", "journal": {"title": "Wiley Analytical Science", "issn": null, "issn-l": null, "volume": "https://analyticalscience.wiley.com/do/10.1002/was.000400044", "issue": null, "pages": null}, "abstract": "Time-lapse imaging allows researchers to follow various processes over time. Applications in life sciences can be as varied as evaluating the role of cell division and migration in developing embryos to the measurement of the moving pattern of living mice. In both of these example cases the process can be quantified using single particle tracking.\r\n\r\nA very powerful but still easy to use tool for single particle tracking is TrackMate \u2013 which comes as a plugin within Fiji [1,2]. This article gives an overview of the functionalities of TrackMate.", "doi": "10.1002/was.000400044", "pmid": null, "labels": {"BioImage Informatics": "Technology development", "Bioinformatics (NBIS)": "Technology development"}, "xrefs": [], "notes": [], "created": "2020-11-30T10:49:04.452Z", "modified": "2022-03-29T11:52:12.843Z"}, {"entity": "publication", "iuid": "cacdffc5e9214e87a523552b26690a9b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cacdffc5e9214e87a523552b26690a9b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cacdffc5e9214e87a523552b26690a9b"}}, "title": "Evaluation of Single-Molecule Sequencing Technologies for Structural Variant Detection in Two Swedish Human Genomes.", "authors": [{"family": "Fatima", "given": "Nazeefa", "initials": "N", "orcid": "0000-0001-7791-4984", "researcher": {"href": "https://publications.scilifelab.se/researcher/4b6d2aa00c99444da15a97a9a0478568.json"}}, {"family": "Petri", "given": "Anna", "initials": "A"}, {"family": "Gyllensten", "given": "Ulf", "initials": "U"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}], "type": "journal article", "published": "2020-11-30", "journal": {"title": "Genes", "issn": "2073-4425", "volume": "11", "issue": "12", "pages": "1444", "issn-l": "2073-4425"}, "abstract": "Long-read single molecule sequencing is increasingly used in human genomics research, as it allows to accurately detect large-scale DNA rearrangements such as structural variations (SVs) at high resolution. However, few studies have evaluated the performance of different single molecule sequencing platforms for SV detection in human samples. Here we performed Oxford Nanopore Technologies (ONT) whole-genome sequencing of two Swedish human samples (average 32\u00d7 coverage) and compared the results to previously generated Pacific Biosciences (PacBio) data for the same individuals (average 66\u00d7 coverage). Our analysis inferred an average of 17k and 23k SVs from the ONT and PacBio data, respectively, with a majority of them overlapping with an available multi-platform SV dataset. When comparing the SV calls in the two Swedish individuals, we find a higher concordance between ONT and PacBio SVs detected in the same individual as compared to SVs detected by the same technology in different individuals. Downsampling of PacBio reads, performed to obtain similar coverage levels for all datasets, resulted in 17k SVs per individual and improved overlap with the ONT SVs. Our results suggest that ONT and PacBio have a similar performance for SV detection in human whole genome sequencing data, and that both technologies are feasible for population-scale studies.", "doi": "10.3390/genes11121444", "pmid": "33266238", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Technology development", "National Genomics Infrastructure": "Technology development", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "genes11121444"}, {"db": "pmc", "key": "PMC7760597"}], "notes": [], "created": "2020-12-03T21:45:04.193Z", "modified": "2024-01-16T13:48:41.275Z"}, {"entity": "publication", "iuid": "3e21cc6163c14d55a5a03727b870e2d1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3e21cc6163c14d55a5a03727b870e2d1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3e21cc6163c14d55a5a03727b870e2d1"}}, "title": "Competitive mapping allows for the identification and exclusion of human DNA contamination in ancient faunal genomic datasets.", "authors": [{"family": "Feuerborn", "given": "Tatiana R", "initials": "TR"}, {"family": "Palkopoulou", "given": "Eleftheria", "initials": "E"}, {"family": "van der Valk", "given": "Tom", "initials": "T"}, {"family": "von Seth", "given": "Johanna", "initials": "J"}, {"family": "Munters", "given": "Arielle R", "initials": "AR"}, {"family": "Pe\u010dnerov\u00e1", "given": "Patr\u00edcia", "initials": "P"}, {"family": "Dehasque", "given": "Marianne", "initials": "M"}, {"family": "Ure\u00f1a", "given": "Irene", "initials": "I"}, {"family": "Ersmark", "given": "Erik", "initials": "E"}, {"family": "Lagerholm", "given": "Vendela Kempe", "initials": "VK"}, {"family": "Krzewi\u0144ska", "given": "Maja", "initials": "M"}, {"family": "Rodr\u00edguez-Varela", "given": "Ricardo", "initials": "R"}, {"family": "G\u00f6therstr\u00f6m", "given": "Anders", "initials": "A", "orcid": "0000-0001-6307-8188", "researcher": {"href": "https://publications.scilifelab.se/researcher/2a1a0a680ab8456cbf5a941e9718fd5a.json"}}, {"family": "Dal\u00e9n", "given": "Love", "initials": "L", "orcid": "0000-0001-8270-7613", "researcher": {"href": "https://publications.scilifelab.se/researcher/48ecf726779249ac9d12f4f7a1cc62bf.json"}}, {"family": "D\u00edez-Del-Molino", "given": "David", "initials": "D", "orcid": "0000-0002-9701-5940", "researcher": {"href": "https://publications.scilifelab.se/researcher/abb3bf815a954e039100104597097b68.json"}}], "type": "journal article", "published": "2020-11-30", "journal": {"title": "BMC Genomics", "issn": "1471-2164", "volume": "21", "issue": "1", "pages": "844", "issn-l": "1471-2164"}, "abstract": "After over a decade of developments in field collection, laboratory methods and advances in high-throughput sequencing, contamination remains a key issue in ancient DNA research. Currently, human and microbial contaminant DNA still impose challenges on cost-effective sequencing and accurate interpretation of ancient DNA data.\n\nHere we investigate whether human contaminating DNA can be found in ancient faunal sequencing datasets. We identify variable levels of human contamination, which persists even after the sequence reads have been mapped to the faunal reference genomes. This contamination has the potential to affect a range of downstream analyses.\n\nWe propose a fast and simple method, based on competitive mapping, which allows identifying and removing human contamination from ancient faunal DNA datasets with limited losses of true ancient data. This method could represent an important tool for the ancient DNA field.", "doi": "10.1186/s12864-020-07229-y", "pmid": "33256612", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12864-020-07229-y"}, {"db": "pmc", "key": "PMC7708127"}], "notes": [], "created": "2020-12-07T16:36:42.754Z", "modified": "2024-01-16T13:48:41.282Z"}, {"entity": "publication", "iuid": "5aff66d54e10400292b4d4b1e1ee4a7d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5aff66d54e10400292b4d4b1e1ee4a7d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5aff66d54e10400292b4d4b1e1ee4a7d"}}, "title": "A workflow for high-throughput screening, data analysis, processing, and hit identification", "authors": [{"family": "Hansel", "given": "Catherine S", "initials": "CS"}, {"family": "Yousefian", "given": "Schayan", "initials": "S"}, {"family": "Klemm", "given": "Anna H", "initials": "AH", "orcid": "0000-0002-3466-1320", "researcher": {"href": "https://publications.scilifelab.se/researcher/4ae78afb2a424b0ab70d49871f361d13.json"}}, {"family": "Carreras-Puigvert", "given": "Jordi", "initials": "J"}], "type": null, "published": "2020-11-30", "journal": {"title": "KNIME blog", "issn": null, "issn-l": null, "volume": "https://www.knime.com/blog/a-workflow-for-high-throughput-screening-data-analysis-processing-and-hit-identification", "issue": null, "pages": null}, "abstract": "High-throughput biochemical and phenotypic screening (HTS) is a gold standard technique for drug discovery. Using automation, the effects of thousands of compounds can be evaluated on cultured cells, or using biochemical in vitro assays. By doing so, \u201chit\u201d compounds can be identified that modulate the readout(s) favourably. Since HTS is typically conducted with large compound libraries under several conditions, the raw data generated is often very large and split over a number of spreadsheets/table-like sheets containing data. Therefore, we have created a KNIME workflow to help process and assess large sets of raw data generated from HTS. This workflow automatically imports HTS data and processes it to identify hits with tunable criteria. This means that the user is able to choose different thresholds to identify a compound considered as a hit. Additionally, three commonly used quality control measures, the Z-Prime, signal/background (S/B) and CV, are calculated in the workflow and are visualized in a comprehensive manner.", "doi": null, "pmid": null, "labels": {"BioImage Informatics": "Technology development", "Bioinformatics (NBIS)": "Technology development"}, "xrefs": [], "notes": [], "created": "2020-11-30T10:41:57.095Z", "modified": "2022-03-29T11:53:50.401Z"}, {"entity": "publication", "iuid": "fead16a7ade749c8a101ff49f4a772b3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/fead16a7ade749c8a101ff49f4a772b3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/fead16a7ade749c8a101ff49f4a772b3"}}, "title": "New Insights into the Microbial Profiles of Infected Root Canals in Traumatized Teeth.", "authors": [{"family": "Manoharan", "given": "Lokeshwaran", "initials": "L", "orcid": "0000-0001-9751-5745", "researcher": {"href": "https://publications.scilifelab.se/researcher/000321fd81b9457db66140246bbd9066.json"}}, {"family": "Brundin", "given": "Malin", "initials": "M"}, {"family": "Rakhimova", "given": "Olena", "initials": "O"}, {"family": "Ch\u00e1vez de Paz", "given": "Luis", "initials": "L"}, {"family": "Romani Vestman", "given": "Nelly", "initials": "N", "orcid": "0000-0002-5674-8179", "researcher": {"href": "https://publications.scilifelab.se/researcher/3273e2c1a9cc4af699a0c61d2b52077a.json"}}], "type": "journal article", "published": "2020-11-28", "journal": {"title": "J Clin Med", "issn": "2077-0383", "volume": "9", "issue": "12", "pages": "3877", "issn-l": "2077-0383"}, "abstract": "Traumatic dental injuries in young individuals are often exposed to the invasion of oral microorganisms that leads to pulp necrosis. Infective necrosis in permanent teeth not-fully-developed causes aberrant root formation. Regeneration endodontic treatments (RETs) have shown promising results by promoting continued root development by stem cells. Critical to the success of RET is the thorough disinfection of the pulpal space. To establish effective antimicrobial protocols for root canal disinfection, the invading microorganisms need to be identified. In the present study, we use a combination of culture-based and high-throughput molecular sequencing techniques to investigate the microbial profiles from traumatized teeth (30 cases) and controls, i.e., teeth with pulp infections not caused by trauma (32 cases). Overall, a high microbial diversity in traumatized necrotic teeth was observed. Eubacterium yurii subsps. yurii and margaretiae, as well as key 'bridging oral species' F. nucleatum sp., Polymorphum and Corynebacterium matruchotti, were highly associated with traumatized teeth. The microbial compositions of traumatized teeth differed considerably from those of infected teeth not caused by trauma. Age and tooth position also influence microbial compositions. In conclusion, we show that the root canal microflora of traumatized teeth is highly diverse, and it differs from root canal infections not caused by trauma.", "doi": "10.3390/jcm9123877", "pmid": "33260621", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "jcm9123877"}, {"db": "pmc", "key": "PMC7760719"}], "notes": [], "created": "2020-11-30T10:28:42.776Z", "modified": "2024-01-16T13:48:41.302Z"}, {"entity": "publication", "iuid": "d505916802d745ffaee823c537c2cad6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d505916802d745ffaee823c537c2cad6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d505916802d745ffaee823c537c2cad6"}}, "title": "The Human Adenovirus Type 2 Transcriptome: An Amazing Complexity of Alternatively Spliced mRNAs.", "authors": [{"family": "Westergren Jakobsson", "given": "Amanda", "initials": "A"}, {"family": "Segerman", "given": "Bo", "initials": "B"}, {"family": "Wallerman", "given": "Ola", "initials": "O"}, {"family": "Lind", "given": "Sara Bergstr\u00f6m", "initials": "SB"}, {"family": "Zhao", "given": "Hongxing", "initials": "H"}, {"family": "Rubin", "given": "Carl-Johan", "initials": "CJ"}, {"family": "Pettersson", "given": "Ulf", "initials": "U"}, {"family": "Akusj\u00e4rvi", "given": "G\u00f6ran", "initials": "G", "orcid": "0000-0003-2961-5060", "researcher": {"href": "https://publications.scilifelab.se/researcher/e61349b53aba497288dd44f3e643fdf8.json"}}], "type": "journal article", "published": "2020-11-25", "journal": {"title": "J. Virol.", "issn": "1098-5514", "issn-l": "0022-538X"}, "abstract": "We have used the Nanopore long-read sequencing platform to demonstrate how amazingly complex the human adenovirus type 2 (Ad2) transcriptome is with a flexible splicing machinery producing a range of novel mRNAs both from the early and late transcription units. In total we report more than 900 alternatively spliced mRNAs produced from the Ad2 transcriptome whereof more than 850 are novel mRNAs. A surprising finding was that more than 50% of all E1A transcripts extended upstream of the previously defined transcriptional start site. The novel start sites mapped close to the inverted terminal repeat (ITR) and within the E1A enhancer region. We speculate that novel promoters or enhancer driven transcription, so-called eRNA transcription, is responsible for producing these novel mRNAs. Their existence was verified by a peptide in the Ad2 proteome that was unique for the E1A ITR mRNA. Although we show a high complexity of alternative splicing from most early and late regions, the E3 region was by far the most complex when expressed at late times of infection. More than 400 alternatively spliced mRNAs were observed in this region alone. These mRNAs included extended L4 mRNAs containing E3 and L5 sequences and readthrough mRNAs combining E3 and L5 sequences. Our findings demonstrate that the virus has a remarkable capacity to produce novel exon combinations, which will offer the virus an evolutionary advantage to change the gene expression repertoire and protein production in an evolving environment.IMPORTANCE Work in the adenovirus system led to the groundbreaking discovery of RNA splicing and alternative RNA splicing in 1977. These mechanisms are essential in mammalian evolution by increasing the coding capacity of a genome. Here, we have used a long-read sequencing technology to characterize the complexity of human adenovirus pre-mRNA splicing in detail. It is mindboggling that the viral genome, which only houses around 36,000 bp, not being much larger than a single cellular gene, generates more than 900 alternatively spliced mRNAs. Recently, adenoviruses have been used as the backbone in several promising SARS-CoV-2 vaccines. Further improvement of adenovirus-based vaccines demands that the virus can be tamed into an innocent carrier of foreign genes. This requires a full understanding of the components that govern adenovirus replication and gene expression.", "doi": "10.1128/JVI.01869-20", "pmid": "33239457", "labels": {"Bioinformatics Support, Infrastructure and Training": "Service", "Bioinformatics Support and Infrastructure": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pii", "key": "JVI.01869-20"}, {"db": "pmc", "key": "PMC7851563"}], "notes": [], "created": "2021-12-02T14:21:44.993Z", "modified": "2021-12-02T14:21:45.035Z"}, {"entity": "publication", "iuid": "0524f50dac7c4bf185787279724e5644", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0524f50dac7c4bf185787279724e5644.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0524f50dac7c4bf185787279724e5644"}}, "title": "Immobilization of sulfate and thiosulfate-reducing biomass on sand under haloalkaline conditions.", "authors": [{"family": "Sousa", "given": "Jo\u00e3o A B", "initials": "JAB"}, {"family": "Bolg\u00e1r", "given": "Andrea", "initials": "A"}, {"family": "Christel", "given": "Stephan", "initials": "S"}, {"family": "Dopson", "given": "Mark", "initials": "M", "orcid": "0000-0002-9622-3318", "researcher": {"href": "https://publications.scilifelab.se/researcher/1dc9cc6dadf6483e88d855dc78709a59.json"}}, {"family": "Bijmans", "given": "Martijn F M", "initials": "MFM"}, {"family": "Stams", "given": "Alfons J M", "initials": "AJM"}, {"family": "Plugge", "given": "Caroline M", "initials": "CM", "orcid": "0000-0002-3391-7742", "researcher": {"href": "https://publications.scilifelab.se/researcher/ec1ba6106ef140598f83f1c73ec2b285.json"}}], "type": "journal article", "published": "2020-11-25", "journal": {"title": "Sci. Total Environ.", "issn": "1879-1026", "volume": "745", "issue": null, "pages": "141017", "issn-l": "0048-9697"}, "abstract": "Biological sulfate and thiosulfate reduction under haloalkaline conditions can be applied to treat waste streams from biodesulfurization systems. However, the lack of microbial aggregation under haloalkaline conditions limits the volumetric rates of sulfate and thiosulfate reducing bioreactors. As biomass retention in haloalkaline bioreactors has not been studied before, sand was chosen as a biomass carrier material to increase cell retention and consequently raise the volumetric rates. The results showed that ~10 fold higher biomass concentrations could be achieved with sand, compared to previous studies without carrier addition. The volumetric rates of sulfate/thiosulfate reduction increased approximately 4.5 times. Biomass attachment to the sand was restricted to cavities within the sand particles. Acetate produced by acetogenic bacteria from H2 and CO2 was used as carbon source for biomass growth, while formate that was also produced from H2 and CO2 enhanced sulfate reduction. The microbial community composition was analyzed by 16S rRNA gene amplicon sequencing, and Tindallia related bacteria were probably responsible for formate formation from hydrogen. The community attached to the sand particles was similar to the suspended fraction, but the relative abundance of sequences most closely related to Desulfohalobiaceae was much higher in the attached fraction compared to the suspended fraction (30% and 13%, respectively). The results indicated that even though the biomass attachment to sand was poor, it still increased the biomass concentration and consequently the sulfate and thiosulfate reduction volumetric rates.", "doi": "10.1016/j.scitotenv.2020.141017", "pmid": "32736107", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service"}, "xrefs": [{"db": "pii", "key": "S0048-9697(20)34546-0"}], "notes": [], "created": "2020-12-07T16:29:56.594Z", "modified": "2021-11-10T12:45:01.994Z"}, {"entity": "publication", "iuid": "aac256774d0444cdbb512faa4cd1b346", "links": {"self": {"href": "https://publications.scilifelab.se/publication/aac256774d0444cdbb512faa4cd1b346.json"}, "display": {"href": "https://publications.scilifelab.se/publication/aac256774d0444cdbb512faa4cd1b346"}}, "title": "Genome-wide identification of Argonautes in Solanaceae with emphasis on potato.", "authors": [{"family": "Liao", "given": "Zhen", "initials": "Z"}, {"family": "Hod\u00e9n", "given": "Kristian Persson", "initials": "KP"}, {"family": "Singh", "given": "Ravi Kumar", "initials": "RK"}, {"family": "Dixelius", "given": "Christina", "initials": "C"}], "type": "journal article", "published": "2020-11-25", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "20577", "issn-l": "2045-2322"}, "abstract": "Regulatory small RNAs (sRNAs) play important roles in many fundamental processes in plant biology such as development, fertilization and stress responses. The AGO protein family has here a central importance in gene regulation based on their capacity to associate with sRNAs followed by mRNA targeting in a sequence-complementary manner. The present study explored Argonautes (AGOs) in the Solanaceae family, with emphasis on potato, Solanum tuberosum (St). A genome-wide monitoring was performed to provide a deeper insight into gene families, genomic localization, gene structure and expression profile against the potato late blight pathogen Phytophthora infestans. Among 15 species in the Solanaceae family we found a variation from ten AGOs in Nicotiana obtusifolia to 17 in N. tabacum. Comprehensive analyses of AGO phylogeny revealed duplication of AGO1, AGO10 and AGO4 paralogs during early radiation of Solanaceae. Fourteen AGOs were identified in potato. Orthologs of AGO8 and AGO9 were missing in the potato genome. However, AGO15 earlier annotated in tomato was identified. StAGO15 differs from the other paralogs having residues of different physico-chemical properties at functionally important amino acid positions. Upon pathogen challenge StAGO15 was significantly activated and hence may play a prominent role in sRNA-based regulation of potato defense.", "doi": "10.1038/s41598-020-77593-y", "pmid": "33239724", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-77593-y"}, {"db": "pmc", "key": "PMC7689493"}], "notes": [], "created": "2020-12-07T16:36:39.190Z", "modified": "2021-11-10T12:45:03.177Z"}, {"entity": "publication", "iuid": "f5382fa2acda4d9c8e8301fb63479538", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f5382fa2acda4d9c8e8301fb63479538.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f5382fa2acda4d9c8e8301fb63479538"}}, "title": "\u03b1-Synuclein promotes IAPP fibril formation in vitro and \u03b2-cell amyloid formation in vivo in mice.", "authors": [{"family": "Mucibabic", "given": "Marija", "initials": "M"}, {"family": "Steneberg", "given": "P\u00e4r", "initials": "P"}, {"family": "Lidh", "given": "Emmelie", "initials": "E"}, {"family": "Straseviciene", "given": "Jurate", "initials": "J"}, {"family": "Ziolkowska", "given": "Agnieszka", "initials": "A", "orcid": "0000-0002-4262-7106", "researcher": {"href": "https://publications.scilifelab.se/researcher/1355ff26d9cf4626bad7b3b93bf0a90d.json"}}, {"family": "Dahl", "given": "Ulf", "initials": "U"}, {"family": "Lindahl", "given": "Emma", "initials": "E", "orcid": "0000-0003-1333-5398", "researcher": {"href": "https://publications.scilifelab.se/researcher/51600cedcf044bdda0f677deaeaf9fad.json"}}, {"family": "Edlund", "given": "Helena", "initials": "H"}], "type": "journal article", "published": "2020-11-24", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "20438", "issn-l": "2045-2322"}, "abstract": "Type 2 diabetes (T2D), alike Parkinson's disease (PD), belongs to the group of protein misfolding diseases (PMDs), which share aggregation of misfolded proteins as a hallmark. Although the major aggregating peptide in \u03b2-cells of T2D patients is Islet Amyloid Polypeptide (IAPP), alpha-synuclein (\u03b1Syn), the aggregating peptide in substantia nigra neurons of PD patients, is expressed also in \u03b2-cells. Here we show that \u03b1Syn, encoded by Snca, is a component of amyloid extracted from pancreas of transgenic mice overexpressing human IAPP (denoted hIAPPtg mice) and from islets of T2D individuals. Notably, \u03b1Syn dose-dependently promoted IAPP fibril formation in vitro and tail-vein injection of \u03b1Syn in hIAPPtg mice enhanced \u03b2-cell amyloid formation in vivo whereas \u03b2-cell amyloid formation was reduced in hIAPPtg mice on a Snca -/- background. Taken together, our findings provide evidence that \u03b1Syn and IAPP co-aggregate both in vitro and in vivo, suggesting a role for \u03b1Syn in \u03b2-cell amyloid formation.", "doi": "10.1038/s41598-020-77409-z", "pmid": "33235246", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-77409-z"}, {"db": "pmc", "key": "PMC7686322"}], "notes": [], "created": "2020-12-10T11:07:23.272Z", "modified": "2023-12-04T10:15:38.252Z"}, {"entity": "publication", "iuid": "6d14e16e79174f66ab22f273f4b61098", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6d14e16e79174f66ab22f273f4b61098.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6d14e16e79174f66ab22f273f4b61098"}}, "title": "Variations among Viruses in Influent Water and Effluent Water at a Wastewater Plant over One Year as Assessed by Quantitative PCR and Metagenomics.", "authors": [{"family": "Wang", "given": "Hao", "initials": "H"}, {"family": "Neyvaldt", "given": "Julianna", "initials": "J"}, {"family": "Enache", "given": "Lucica", "initials": "L"}, {"family": "Sikora", "given": "Per", "initials": "P"}, {"family": "Mattsson", "given": "Ann", "initials": "A"}, {"family": "Johansson", "given": "Anette", "initials": "A"}, {"family": "Lindh", "given": "Magnus", "initials": "M"}, {"family": "Bergstedt", "given": "Olof", "initials": "O"}, {"family": "Norder", "given": "Helene", "initials": "H", "orcid": "0000-0002-7528-3872", "researcher": {"href": "https://publications.scilifelab.se/researcher/96f9ac68626f4796840da78e72940193.json"}}], "type": "journal article", "published": "2020-11-24", "journal": {"title": "Appl. Environ. Microbiol.", "issn": "1098-5336", "volume": "86", "issue": "24", "issn-l": "0099-2240"}, "abstract": "Influent wastewater and effluent wastewater at the Rya treatment plant in Gothenburg, Sweden, were continuously monitored for enteric viruses by quantitative PCR (qPCR) during 1 year. Viruses in effluent wastewater were also identified by next-generation sequencing (NGS) in samples collected during spring, early summer, and winter. Samples of incoming wastewater were collected every second week. Seasonal variations in viral concentrations in incoming wastewater were found for noroviruses GII, sapovirus, rotavirus, parechovirus, and astrovirus. Norovirus GI and GIV and Aichi virus were present in various amounts during most weeks throughout the year, while hepatitis A virus, enterovirus, and adenovirus were identified less frequently. Fluctuations in viral concentrations in incoming wastewater were related to the number of diagnosed patients. The viruses were also detected in treated wastewater, however, with a 3- to 6-log10 reduction in concentration. Seven different hepatitis E virus (HEV) strains were identified in the effluents. Five of these strains belonged to genotype 3 and have been isolated in Sweden from swine, wild boars, and humans and in drinking water. The other two strains were divergent and had not been identified previously. They were similar to strains infecting rats and humans. Surveillance of enteric viruses in wastewater is a tool for early detection and follow-up of gastroenteritis outbreaks in society and for the identification of new viruses that can cause infection in humans.IMPORTANCE Both influent wastewater and treated wastewater at a wastewater treatment plant (WWTP) contain a high variety of human viral pathogens with seasonal variability when followed for 1 year. The peak of the amount of 11 different viruses in the inlet wastewater preceded the peak of the number of diagnosed patients by 2 to 4 weeks. The treatment of wastewater reduced viral concentrations by 3 to 6 log10 Despite the treatment of wastewater, up to 5 log10 virus particles per liter were released from into the surrounding river. Hepatitis E virus (HEV) strains previously identified in drinking water and two new strains, similar to those infecting rats and humans, were identified in the treated wastewater released from the WWTP.", "doi": "10.1128/AEM.02073-20", "pmid": "33036988", "labels": {"Clinical Genomics Gothenburg": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "AEM.02073-20"}, {"db": "pmc", "key": "PMC7688244"}], "notes": [], "created": "2022-03-29T13:36:04.916Z", "modified": "2022-03-29T13:37:56.509Z"}, {"entity": "publication", "iuid": "fff3f8ee4ff74f7c80d36a32e38892fe", "links": {"self": {"href": "https://publications.scilifelab.se/publication/fff3f8ee4ff74f7c80d36a32e38892fe.json"}, "display": {"href": "https://publications.scilifelab.se/publication/fff3f8ee4ff74f7c80d36a32e38892fe"}}, "title": "Structure dynamics of ApoA-I amyloidogenic variants in small HDL increase their ability to mediate cholesterol efflux.", "authors": [{"family": "Nilsson", "given": "Oktawia", "initials": "O"}, {"family": "Lindvall", "given": "Mikaela", "initials": "M"}, {"family": "Obici", "given": "Laura", "initials": "L"}, {"family": "Ekstr\u00f6m", "given": "Simon", "initials": "S"}, {"family": "Lagerstedt", "given": "Jens O", "initials": "JO"}, {"family": "Del Giudice", "given": "Rita", "initials": "R"}], "type": "journal article", "published": "2020-11-24", "journal": {"title": "J. Lipid Res.", "issn": "1539-7262", "volume": "62", "pages": "100004", "issn-l": "0022-2275"}, "abstract": "Apolipoprotein A-I (ApoA-I) of high density lipoproteins (HDLs) is essential for the transportation of cholesterol between peripheral tissues and the liver. However, specific mutations in ApoA-I of HDLs are responsible for a late-onset systemic amyloidosis, the pathological accumulation of protein fibrils in tissues and organs. Carriers of these mutations do not exhibit increased cardiovascular disease risk despite displaying reduced levels of ApoA-I/HDL cholesterol. To explain this paradox, we show that the HDL particle profiles of patients carrying either L75P or L174S ApoA-I amyloidogenic variants show a higher relative abundance of the 8.4-nm versus 9.6-nm particles and that serum from patients, as well as reconstituted 8.4- and 9.6-nm HDL particles (rHDL), possess increased capacity to catalyze cholesterol efflux from macrophages. Synchrotron radiation circular dichroism and hydrogen-deuterium exchange revealed that the variants in 8.4-nm rHDL have altered secondary structure composition and display a more flexible binding to lipids than their native counterpart. The reduced HDL cholesterol levels of patients carrying ApoA-I amyloidogenic variants are thus balanced by higher proportion of small, dense HDL particles, and better cholesterol efflux due to altered, region-specific protein structure dynamics.", "doi": "10.1194/jlr.RA120000920", "pmid": "33410751", "labels": {"Structural Proteomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0022-2275(20)43706-X"}, {"db": "pmc", "key": "PMC7890215"}], "notes": [], "created": "2021-12-03T09:37:31.362Z", "modified": "2021-12-03T09:37:31.367Z"}, {"entity": "publication", "iuid": "4fb5d06e3be24800b8c60fd0a947e6b9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4fb5d06e3be24800b8c60fd0a947e6b9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4fb5d06e3be24800b8c60fd0a947e6b9"}}, "title": "High CD45 expression of CD8+ and CD4+ T cells correlates with the size of HIV-1 reservoir in blood.", "authors": [{"family": "Petkov", "given": "Stefan", "initials": "S"}, {"family": "Bekele", "given": "Yonas", "initials": "Y"}, {"family": "Lakshmikanth", "given": "Tadepally", "initials": "T", "orcid": "0000-0001-7256-5770", "researcher": {"href": "https://publications.scilifelab.se/researcher/92e81aa6b0cf4ff0a18b14098bf0fcc1.json"}}, {"family": "Hejdeman", "given": "Bo", "initials": "B"}, {"family": "Zazzi", "given": "Maurizio", "initials": "M"}, {"family": "Brodin", "given": "Petter", "initials": "P", "orcid": "0000-0002-8103-0046", "researcher": {"href": "https://publications.scilifelab.se/researcher/40097353cdb24e52bf2330eb687042bf.json"}}, {"family": "Chiodi", "given": "Francesca", "initials": "F"}], "type": "journal article", "published": "2020-11-24", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "20425", "issn-l": "2045-2322"}, "abstract": "Using mass cytometry, we investigated the expression of 28 markers on CD8+ and CD4+ T cells from HIV-1 infected patients with a variable size of HIV-1 reservoir defined as high (HR) and low (LR) reservoir; we aimed at identifying phenotypic associations of T cells with size of HIV-1 reservoir. We showed that the frequency of CD45+ CD8+ and CD4+ T cells was directly proportional to the size of HIV-1 reservoir; HR patients had a significantly larger frequency of blood CD45high T cells and higher CD45 expression on both CD8+ and CD4+ T cells. CD45 is a receptor-type protein tyrosine phosphatase essential in TCR signaling. Functional and phenotypical analysis of CD45high cells revealed that they express activation and proliferation markers (CD38 + HLA-DR + and Ki-67) and produce cytokines upon in vitro activation. CD45high T cells also expressed high levels of immune check-point PD-1. Our results link CD45 expression on T cells to HIV-1 reservoir; PD-1 expression on CD45high T cells may contribute to their exhaustion.", "doi": "10.1038/s41598-020-77433-z", "pmid": "33235273", "labels": {"Cellular Immunomonitoring": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-77433-z"}, {"db": "pmc", "key": "PMC7686502"}], "notes": [], "created": "2020-11-30T08:25:42.449Z", "modified": "2024-01-16T13:48:41.309Z"}, {"entity": "publication", "iuid": "29d8a642e60f4a8ca18b324c9ff46682", "links": {"self": {"href": "https://publications.scilifelab.se/publication/29d8a642e60f4a8ca18b324c9ff46682.json"}, "display": {"href": "https://publications.scilifelab.se/publication/29d8a642e60f4a8ca18b324c9ff46682"}}, "title": "Inactivation of mediator complex protein 22 in podocytes results in intracellular vacuole formation, podocyte loss and premature death.", "authors": [{"family": "Rodriguez", "given": "Patricia Q", "initials": "PQ"}, {"family": "Unnersj\u00f6-Jess", "given": "David", "initials": "D"}, {"family": "Zambrano", "given": "Sonia S", "initials": "SS"}, {"family": "Guo", "given": "Jing", "initials": "J"}, {"family": "M\u00f6ller-Hackbarth", "given": "Katja", "initials": "K"}, {"family": "Blom", "given": "Hans", "initials": "H", "orcid": "0000-0002-5584-9170", "researcher": {"href": "https://publications.scilifelab.se/researcher/3ce356a74dc84e0ea6af85397f11d869.json"}}, {"family": "Jahnukainen", "given": "Timo", "initials": "T"}, {"family": "Ebarasi", "given": "Lwaki", "initials": "L"}, {"family": "Patrakka", "given": "Jaakko", "initials": "J"}], "type": "journal article", "published": "2020-11-18", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "20037", "issn-l": "2045-2322"}, "abstract": "Podocytes are critical for the maintenance of kidney ultrafiltration barrier and play a key role in the progression of glomerular diseases. Although mediator complex proteins have been shown to be important for many physiological and pathological processes, their role in kidney tissue has not been studied. In this study, we identified a mediator complex protein 22 (Med22) as a renal podocyte cell-enriched molecule. Podocyte-specific Med22 knockout mouse showed that Med22 was not needed for normal podocyte maturation. However, it was critical for the maintenance of podocyte health as the mice developed progressive glomerular disease and died due to renal failure. Detailed morphological analyses showed that Med22-deficiency in podocytes resulted in intracellular vacuole formation followed by podocyte loss. Moreover, Med22-deficiency in younger mice promoted the progression of glomerular disease, suggesting Med22-mediated processes may have a role in the development of glomerulopathies. This study shows for the first time that mediator complex has a critical role in kidney physiology.", "doi": "10.1038/s41598-020-76870-0", "pmid": "33208756", "labels": {"Integrated Microscopy Technologies Stockholm": "Technology development"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-76870-0"}, {"db": "pmc", "key": "PMC7676236"}], "notes": [], "created": "2020-11-18T16:01:37.186Z", "modified": "2021-11-10T12:45:08.719Z"}, {"entity": "publication", "iuid": "c54fad9a92ff45be90b06c461c2854cb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c54fad9a92ff45be90b06c461c2854cb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c54fad9a92ff45be90b06c461c2854cb"}}, "title": "Exploring autoantibody signatures in brain tissue from patients with severe mental illness.", "authors": [{"family": "Just", "given": "David", "initials": "D", "orcid": "0000-0001-6126-2256", "researcher": {"href": "https://publications.scilifelab.se/researcher/46f687d3a9cf4400932c75510807c764.json"}}, {"family": "M\u00e5nberg", "given": "Anna", "initials": "A", "orcid": "0000-0002-0056-1313", "researcher": {"href": "https://publications.scilifelab.se/researcher/6d155273b5b54e61b773f263e4f2ce9b.json"}}, {"family": "Mitsios", "given": "Nicholas", "initials": "N", "orcid": "0000-0001-6243-4953", "researcher": {"href": "https://publications.scilifelab.se/researcher/38efa44f5ed64192b432d6384584f00d.json"}}, {"family": "Stockmeier", "given": "Craig A", "initials": "CA", "orcid": "0000-0003-1861-1013", "researcher": {"href": "https://publications.scilifelab.se/researcher/89ebb5b73b9a42498192d35aea2d92c5.json"}}, {"family": "Rajkowska", "given": "Grazyna", "initials": "G", "orcid": "0000-0002-4348-4688", "researcher": {"href": "https://publications.scilifelab.se/researcher/4122635fead74359983624753ee365ff.json"}}, {"family": "Uhl\u00e9n", "given": "Mathias", "initials": "M", "orcid": "0000-0002-4858-8056", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff81da3cb0cf4262873b993a1b06798c.json"}}, {"family": "Mulder", "given": "Jan", "initials": "J", "orcid": "0000-0003-3717-5018", "researcher": {"href": "https://publications.scilifelab.se/researcher/a8443b271929476bb2b569e39bae732c.json"}}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Cunningham", "given": "Janet L", "initials": "JL", "orcid": "0000-0001-7876-7779", "researcher": {"href": "https://publications.scilifelab.se/researcher/3ab30dd6c6874bc7a227a8699c4a7085.json"}}, {"family": "Nilsson", "given": "Peter", "initials": "P", "orcid": "0000-0002-4657-8532", "researcher": {"href": "https://publications.scilifelab.se/researcher/799bcf1cf8cf451296f4535dd4ca9dc0.json"}}, {"family": "Carlstr\u00f6m", "given": "Eva Lindholm", "initials": "EL", "orcid": "0000-0001-8055-7826", "researcher": {"href": "https://publications.scilifelab.se/researcher/c433744d926b450097e71784b8bcc27c.json"}}], "type": "journal article", "published": "2020-11-18", "journal": {"title": "Transl Psychiatry", "issn": "2158-3188", "volume": "10", "issue": "1", "pages": "401", "issn-l": "2158-3188"}, "abstract": "In recent years, studies have shown higher prevalence of autoantibodies in patients with schizophrenia compared to healthy individuals. This study applies an untargeted and a targeted affinity proteomics approach to explore and characterize the autoantibody repertoire in brain tissues from 73 subjects diagnosed with schizophrenia and 52 control subjects with no psychiatric or neurological disorders. Selected brain tissue lysates were first explored for IgG reactivity on planar microarrays composed of 11,520 protein fragments representing 10,820 unique proteins. Based on these results of ours and other previous studies of autoantibodies related to psychosis, we selected 226 fragments with an average length of 80 amino acids, representing 127 unique proteins. Tissue-based analysis of IgG reactivities using antigen suspension bead arrays was performed in a multiplex and parallel fashion for all 125 subjects. Among the detected autoantigens, higher IgG reactivity in subjects with schizophrenia, as compared to psychiatrically healthy subjects, was found against the glutamate ionotropic receptor NMDA type subunit 2D (anti-GluN2D). In a separate cohort with serum samples from 395 young adults with a wider spectrum of psychiatric disorders, higher levels of serum autoantibodies targeting GluN2D were found when compared to 102 control individuals. By further validating GluN2D and additional potential autoantigens, we will seek insights into how these are associated with severe mental illnesses.", "doi": "10.1038/s41398-020-01079-8", "pmid": "33208725", "labels": {"Autoimmunity and Serology Profiling": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41398-020-01079-8"}, {"db": "pmc", "key": "PMC7676257"}], "notes": [], "created": "2020-11-19T10:26:29.658Z", "modified": "2021-11-10T12:45:09.790Z"}, {"entity": "publication", "iuid": "d9786edd8d5e4150b3faa03d68d049c6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d9786edd8d5e4150b3faa03d68d049c6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d9786edd8d5e4150b3faa03d68d049c6"}}, "title": "A complex DICER1 syndrome phenotype associated with a germline pathogenic variant affecting the RNase IIIa domain of DICER1.", "authors": [{"family": "Pont\u00e9n", "given": "Emeli", "initials": "E", "orcid": "0000-0002-9174-9804", "researcher": {"href": "https://publications.scilifelab.se/researcher/44288e8f9187470d9def77dada73694a.json"}}, {"family": "Frisk", "given": "Sofia", "initials": "S"}, {"family": "Taylan", "given": "Fulya", "initials": "F", "orcid": "0000-0002-2907-0235", "researcher": {"href": "https://publications.scilifelab.se/researcher/c250909cc40f42ff9d6e2f640d12451b.json"}}, {"family": "Vaz", "given": "Raquel", "initials": "R"}, {"family": "Wessman", "given": "Sandra", "initials": "S"}, {"family": "de Kock", "given": "Leanne", "initials": "L", "orcid": "0000-0001-7314-1371", "researcher": {"href": "https://publications.scilifelab.se/researcher/60d4da1ea1ab4784bb227d5702e7584a.json"}}, {"family": "Pal", "given": "Niklas", "initials": "N"}, {"family": "Foulkes", "given": "William D", "initials": "WD", "orcid": "0000-0001-7427-4651", "researcher": {"href": "https://publications.scilifelab.se/researcher/2554bd69c2b44a3482ab0ce1df6e4eda.json"}}, {"family": "Lagerstedt-Robinson", "given": "Kristina", "initials": "K", "orcid": "0000-0001-9848-0468", "researcher": {"href": "https://publications.scilifelab.se/researcher/63d275105d9b4253944abaa311c986ee.json"}}, {"family": "Nordgren", "given": "Ann", "initials": "A", "orcid": "0000-0003-3285-4281", "researcher": {"href": "https://publications.scilifelab.se/researcher/08e74c6ddc27493696beca0883027cdd.json"}}], "type": "journal article", "published": "2020-11-18", "journal": {"title": "J. Med. Genet.", "issn": "1468-6244", "volume": null, "issue": null, "pages": "jmedgenet-2020-107385", "issn-l": "0022-2593"}, "abstract": "Germline pathogenic variants in DICER1 cause DICER1 syndrome, an autosomal dominant, pleiotropic tumour predisposition syndrome with variable expressivity and reduced penetrance for specific dysplastic and neoplastic lesions. Recently, a syndrome with the acronym GLOW (Global developmental delay, Lung cysts, Overgrowth, Wilms tumour) was described in two children with mosaic missense mutations in hotspot residues of the DICER1 RNase IIIb domain.\n\nWhole genome sequencing, exome sequencing, Sanger sequencing, digital PCR and a review of Wilms tumours with DICER1 RNase III domain mutations were performed.\n\nA de novo heterozygous c.4031C>T (p.S1344L) variant in the sequence encoding the RNase IIIa domain of DICER1 was detected. Clinical investigations revealed a phenotype that resembles the GLOW subphenotype of DICER1 syndrome.\n\nThe phenotypic overlap between patients with p.S1344L mutation and GLOW syndrome provide clinical support for recent discoveries that RNase IIIa-Ser1344 site mutations impede miRNA-5p biogenesis analogous to DICER1 hotspot mutations in the RNase IIIb domain. We show that an individual with a heterozygous germline p.S1344L mutation has a severe form of DICER1 syndrome ('DICER1 syndrome plus'), with notable features of intellectual disability, macrocephaly, physical abnormalities, Wilms tumour and a well-differentiated fetal adenocarcinoma of the lung.", "doi": "10.1136/jmedgenet-2020-107385", "pmid": "33208384", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "jmedgenet-2020-107385"}], "notes": [], "created": "2020-11-23T08:05:52.969Z", "modified": "2021-11-20T12:18:57.716Z"}, {"entity": "publication", "iuid": "5c901b5af4f94bdf82bd969d255f0767", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5c901b5af4f94bdf82bd969d255f0767.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5c901b5af4f94bdf82bd969d255f0767"}}, "title": "Distinct oligodendrocyte populations have spatial preference and different responses to spinal cord injury", "authors": [{"family": "Floriddia", "given": "Elisa M", "initials": "EM", "orcid": "0000-0003-2304-8114", "researcher": {"href": "https://publications.scilifelab.se/researcher/6ea55e5ce2b74a799fbcce59b53e62ac.json"}}, {"family": "Louren\u00e7o", "given": "T\u00e2nia", "initials": "T"}, {"family": "Zhang", "given": "Shupei", "initials": "S"}, {"family": "van Bruggen", "given": "David", "initials": "D", "orcid": "0000-0001-6794-7731", "researcher": {"href": "https://publications.scilifelab.se/researcher/d613135b6ba740c59062e3e7e4fd8174.json"}}, {"family": "Hilscher", "given": "Markus M", "initials": "MM", "orcid": "0000-0001-7782-0830", "researcher": {"href": "https://publications.scilifelab.se/researcher/1de5317c53f34bc89dabfddb0be44983.json"}}, {"family": "Kukanja", "given": "Petra", "initials": "P", "orcid": "0000-0003-1228-5923", "researcher": {"href": "https://publications.scilifelab.se/researcher/082ef6e681214c14b8ca36cd0188722b.json"}}, {"family": "Gon\u00e7alves dos Santos", "given": "Jo\u00e3o P", "initials": "JP"}, {"family": "Alt\u0131nk\u00f6k", "given": "M\u00fcge", "initials": "M"}, {"family": "Yokota", "given": "Chika", "initials": "C"}, {"family": "Llorens-Bobadilla", "given": "Enric", "initials": "E", "orcid": "0000-0002-7891-1272", "researcher": {"href": "https://publications.scilifelab.se/researcher/3144601c466246cfa70acbe8c7ee00ee.json"}}, {"family": "Mulinyawe", "given": "Sara B", "initials": "SB"}, {"family": "Gr\u00e3os", "given": "M\u00e1rio", "initials": "M", "orcid": "0000-0002-2707-1488", "researcher": {"href": "https://publications.scilifelab.se/researcher/86454440d6754732b4d8f813d399a9ed.json"}}, {"family": "Sun", "given": "Lu O", "initials": "LO", "orcid": "0000-0002-9293-7241", "researcher": {"href": "https://publications.scilifelab.se/researcher/7bfd19d5fc054ae1a0e6c0c6f286daca.json"}}, {"family": "Fris\u00e9n", "given": "Jonas", "initials": "J"}, {"family": "Nilsson", "given": "Mats", "initials": "M", "orcid": "0000-0001-9985-0387", "researcher": {"href": "https://publications.scilifelab.se/researcher/197cf8ba83ba430f9712b2f4d94dc3e5.json"}}, {"family": "Castelo-Branco", "given": "Gon\u00e7alo", "initials": "G", "orcid": "0000-0003-2247-9393", "researcher": {"href": "https://publications.scilifelab.se/researcher/10b1a8fb48114340b8e390ca1f9e3321.json"}}], "type": "journal-article", "published": "2020-11-17", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "11", "issue": "1", "pages": "5860"}, "abstract": "Mature oligodendrocytes (MOLs) show transcriptional heterogeneity, the functional consequences of which are unclear. MOL heterogeneity might correlate with the local environment or their interactions with different neuron types. Here, we show that distinct MOL populations have spatial preference in the mammalian central nervous system (CNS). We found that MOL type 2 (MOL2) is enriched in the spinal cord when compared to the brain, while MOL types 5 and 6 (MOL5/6) increase their contribution to the OL lineage with age in all analyzed regions. MOL2 and MOL5/6 also have distinct spatial preference in the spinal cord regions where motor and sensory tracts run. OL progenitor cells (OPCs) are not specified into distinct MOL populations during development, excluding a major contribution of OPC intrinsic mechanisms determining MOL heterogeneity. In disease, MOL2 and MOL5/6 present different susceptibility during the chronic phase following traumatic spinal cord injury. Our results demonstrate that the distinct MOL populations have different spatial preference and different responses to disease.", "doi": "10.1038/s41467-020-19453-x", "pmid": "33203872", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Eukaryotic Single Cell Genomics (ESCG)": "Service", "Bioinformatics Support for Computational Resources": "Service", "In Situ Sequencing": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7673029"}, {"db": "pii", "key": "10.1038/s41467-020-19453-x"}], "notes": [], "created": "2020-12-07T16:36:40.432Z", "modified": "2025-10-17T13:02:18.056Z"}, {"entity": "publication", "iuid": "5f2e4baa8bb24a13a4e27bafb78c7f35", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5f2e4baa8bb24a13a4e27bafb78c7f35.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5f2e4baa8bb24a13a4e27bafb78c7f35"}}, "title": "Association between Aquatic Micropollutant Dissipation and River Sediment Bacterial Communities.", "authors": [{"family": "Coll", "given": "Claudia", "initials": "C", "orcid": "0000-0003-1100-1263", "researcher": {"href": "https://publications.scilifelab.se/researcher/d5bdee5b986a4dfda04324367a6a8c4f.json"}}, {"family": "Bier", "given": "Raven", "initials": "R"}, {"family": "Li", "given": "Zhe", "initials": "Z", "orcid": "0000-0002-2379-0768", "researcher": {"href": "https://publications.scilifelab.se/researcher/45eed765d4944b9ebe33a7f4536ce36f.json"}}, {"family": "Langenheder", "given": "Silke", "initials": "S"}, {"family": "Gorokhova", "given": "Elena", "initials": "E"}, {"family": "Sobek", "given": "Anna", "initials": "A", "orcid": "0000-0002-1549-7449", "researcher": {"href": "https://publications.scilifelab.se/researcher/4d5f089d428b4c1b9b0805dcbf4c6fbc.json"}}], "type": "journal article", "published": "2020-11-17", "journal": {"title": "Environ. Sci. Technol.", "issn": "1520-5851", "volume": "54", "issue": "22", "pages": "14380-14392", "issn-l": "0013-936X"}, "abstract": "Assessment of micropollutant biodegradation is essential to determine the persistence of potentially hazardous chemicals in aquatic ecosystems. We studied the dissipation half-lives of 10 micropollutants in sediment-water incubations (based on the OECD 308 standard) with sediment from two European rivers sampled upstream and downstream of wastewater treatment plant (WWTP) discharge. Dissipation half-lives (DT50s) were highly variable between the tested compounds, ranging from 1.5 to 772 days. Sediment from one river sampled downstream from the WWTP showed the fastest dissipation of all micropollutants after sediment RNA normalization. By characterizing sediment bacteria using 16S rRNA sequences, bacterial community composition of a sediment was associated with its capacity for dissipating micropollutants. Bacterial amplicon sequence variants of the genera Ralstonia, Pseudomonas, Hyphomicrobium, and Novosphingobium, which are known degraders of contaminants, were significantly more abundant in the sediment incubations where fast dissipation was observed. Our study illuminates the limitations of the OECD 308 standard to account for variation of dissipation rates of micropollutants due to differences in bacterial community composition. This limitation is problematic particularly for those compounds with DT50s close to regulatory persistence criteria. Thus, it is essential to consider bacterial community composition as a source of variability in regulatory biodegradation and persistence assessments.", "doi": "10.1021/acs.est.0c04393", "pmid": "33104348", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7676288"}], "notes": [], "created": "2020-12-08T23:52:07.112Z", "modified": "2021-11-10T12:45:14.866Z"}, {"entity": "publication", "iuid": "4eaba3d139bf427eb332f2f93f77bf0a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4eaba3d139bf427eb332f2f93f77bf0a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4eaba3d139bf427eb332f2f93f77bf0a"}}, "title": "Evaluation of the efficiency of genomic versus pedigree predictions for growth and wood quality traits in Scots pine.", "authors": [{"family": "Calleja-Rodriguez", "given": "Ainhoa", "initials": "A"}, {"family": "Pan", "given": "Jin", "initials": "J"}, {"family": "Funda", "given": "Tomas", "initials": "T"}, {"family": "Chen", "given": "Zhiqiang", "initials": "Z"}, {"family": "Baison", "given": "John", "initials": "J"}, {"family": "Isik", "given": "Fikret", "initials": "F"}, {"family": "Abrahamsson", "given": "Sara", "initials": "S"}, {"family": "Wu", "given": "Harry X", "initials": "HX"}], "type": "journal article", "published": "2020-11-16", "journal": {"title": "BMC Genomics", "issn": "1471-2164", "volume": "21", "issue": "1", "pages": "796", "issn-l": "1471-2164"}, "abstract": "Genomic selection (GS) or genomic prediction is a promising approach for tree breeding to obtain higher genetic gains by shortening time of progeny testing in breeding programs. As proof-of-concept for Scots pine (Pinus sylvestris L.), a genomic prediction study was conducted with 694 individuals representing 183 full-sib families that were genotyped with genotyping-by-sequencing (GBS) and phenotyped for growth and wood quality traits. 8719 SNPs were used to compare different genomic with pedigree prediction models. Additionally, four prediction efficiency methods were used to evaluate the impact of genomic breeding value estimations by assigning diverse ratios of training and validation sets, as well as several subsets of SNP markers.\n\nGenomic Best Linear Unbiased Prediction (GBLUP) and Bayesian Ridge Regression (BRR) combined with expectation maximization (EM) imputation algorithm showed slightly higher prediction efficiencies than Pedigree Best Linear Unbiased Prediction (PBLUP) and Bayesian LASSO, with some exceptions. A subset of approximately 6000 SNP markers, was enough to provide similar prediction efficiencies as the full set of 8719 markers. Additionally, prediction efficiencies of genomic models were enough to achieve a higher selection response, that varied between 50-143% higher than the traditional pedigree-based selection.\n\nAlthough prediction efficiencies were similar for genomic and pedigree models, the relative selection response was doubled for genomic models by assuming that earlier selections can be done at the seedling stage, reducing the progeny testing time, thus shortening the breeding cycle length roughly by 50%.", "doi": "10.1186/s12864-020-07188-4", "pmid": "33198692", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12864-020-07188-4"}, {"db": "pmc", "key": "PMC7667760"}], "notes": [], "created": "2020-12-08T23:32:05.662Z", "modified": "2024-01-16T13:48:41.324Z"}, {"entity": "publication", "iuid": "42d4c81543004808bb8e0671da16b03f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/42d4c81543004808bb8e0671da16b03f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/42d4c81543004808bb8e0671da16b03f"}}, "title": "One-Pot, Metal-Free Synthesis of Dimethyl Carbonate from CO2 at Room Temperature", "authors": [{"family": "Khokarale", "given": "Santosh Govind", "initials": "SG"}, {"family": "Bui", "given": "Thai Q", "initials": "TQ"}, {"family": "Mikkola", "given": "Jyri Pekka", "initials": "JP"}], "type": "journal-article", "published": "2020-11-13", "journal": {"title": "Sustainable Chemistry", "issn": "2673-4079", "volume": "1", "issue": "3", "pages": "298-314", "issn-l": "2673-4079"}, "abstract": null, "doi": "10.3390/suschem1030020", "pmid": null, "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [], "notes": [], "created": "2020-11-24T20:27:49.757Z", "modified": "2025-10-17T13:03:56.468Z"}, {"entity": "publication", "iuid": "846d39f0d96e40b9b583e4a5b0420bef", "links": {"self": {"href": "https://publications.scilifelab.se/publication/846d39f0d96e40b9b583e4a5b0420bef.json"}, "display": {"href": "https://publications.scilifelab.se/publication/846d39f0d96e40b9b583e4a5b0420bef"}}, "title": "Obesity-associated microbiota contributes to mucus layer defects in genetically obese mice.", "authors": [{"family": "Schroeder", "given": "Bjoern O", "initials": "BO"}, {"family": "Birchenough", "given": "George M H", "initials": "GMH"}, {"family": "Pradhan", "given": "Meenakshi", "initials": "M"}, {"family": "Nystr\u00f6m", "given": "Elisabeth E L", "initials": "EEL"}, {"family": "Henricsson", "given": "Marcus", "initials": "M"}, {"family": "Hansson", "given": "Gunnar C", "initials": "GC"}, {"family": "B\u00e4ckhed", "given": "Fredrik", "initials": "F"}], "type": "journal article", "published": "2020-11-13", "journal": {"title": "J. Biol. Chem.", "issn": "1083-351X", "volume": "295", "issue": "46", "pages": "15712-15726", "issn-l": "0021-9258"}, "abstract": "The intestinal mucus layer is a physical barrier separating the tremendous number of gut bacteria from the host epithelium. Defects in the mucus layer have been linked to metabolic diseases, but previous studies predominantly investigated mucus function during high-caloric/low-fiber dietary interventions, thus making it difficult to separate effects mediated directly through diet quality from potential obesity-dependent effects. As such, we decided to examine mucus function in mouse models with metabolic disease to distinguish these factors. Here we show that, in contrast to their lean littermates, genetically obese (ob/ob) mice have a defective inner colonic mucus layer that is characterized by increased penetrability and a reduced mucus growth rate. Exploiting the coprophagic behavior of mice, we next co-housed ob/ob and lean mice to investigate if the gut microbiota contributed to these phenotypes. Co-housing rescued the defect of the mucus growth rate, whereas mucus penetrability displayed an intermediate phenotype in both mouse groups. Of note, non-obese diabetic mice with high blood glucose levels displayed a healthy colonic mucus barrier, indicating that the mucus defect is obesity- rather than glucose-mediated. Thus, our data suggest that the gut microbiota community of obesity-prone mice may regulate obesity-associated defects in the colonic mucosal barrier, even in the presence of dietary fiber.", "doi": "10.1074/jbc.RA120.015771", "pmid": "32900852", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7667970"}, {"db": "pii", "key": "S0021-9258(17)50399-3"}], "notes": [], "created": "2023-02-16T08:09:48.007Z", "modified": "2023-02-16T08:09:48.009Z"}, {"entity": "publication", "iuid": "d3262da1a3d84a52a3326fa53a0aa094", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d3262da1a3d84a52a3326fa53a0aa094.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d3262da1a3d84a52a3326fa53a0aa094"}}, "title": "A ribonucleotide reductase from Clostridium botulinum reveals distinct evolutionary pathways to regulation via the overall activity site.", "authors": [{"family": "Mart\u00ednez-Carranza", "given": "Markel", "initials": "M"}, {"family": "Jonna", "given": "Venkateswara Rao", "initials": "VR"}, {"family": "Lundin", "given": "Daniel", "initials": "D"}, {"family": "Sahlin", "given": "Margareta", "initials": "M"}, {"family": "Carlson", "given": "Lars-Anders", "initials": "LA"}, {"family": "Jemal", "given": "Newal", "initials": "N"}, {"family": "H\u00f6gbom", "given": "Martin", "initials": "M"}, {"family": "Sj\u00f6berg", "given": "Britt-Marie", "initials": "BM", "orcid": "0000-0001-5953-3360", "researcher": {"href": "https://publications.scilifelab.se/researcher/fab276f213364c2eaa6fe3dc5c9b01ff.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications.scilifelab.se/researcher/d97eba9f5edf4d76a5259c4baa8366c5.json"}}, {"family": "Hofer", "given": "Anders", "initials": "A"}], "type": "journal article", "published": "2020-11-13", "journal": {"title": "J. Biol. Chem.", "issn": "1083-351X", "volume": "295", "issue": "46", "pages": "15576-15587", "issn-l": "0021-9258"}, "abstract": "Ribonucleotide reductase (RNR) is a central enzyme for the synthesis of DNA building blocks. Most aerobic organisms, including nearly all eukaryotes, have class I RNRs consisting of R1 and R2 subunits. The catalytic R1 subunit contains an overall activity site that can allosterically turn the enzyme on or off by the binding of ATP or dATP, respectively. The mechanism behind the ability to turn the enzyme off via the R1 subunit involves the formation of different types of R1 oligomers in most studied species and R1-R2 octamers in Escherichia coli To better understand the distribution of different oligomerization mechanisms, we characterized the enzyme from Clostridium botulinum, which belongs to a subclass of class I RNRs not studied before. The recombinantly expressed enzyme was analyzed by size-exclusion chromatography, gas-phase electrophoretic mobility macromolecular analysis, EM, X-ray crystallography, and enzyme assays. Interestingly, it shares the ability of the E. coli RNR to form inhibited R1-R2 octamers in the presence of dATP but, unlike the E. coli enzyme, cannot be turned off by combinations of ATP and dGTP/dTTP. A phylogenetic analysis of class I RNRs suggests that activity regulation is not ancestral but was gained after the first subclasses diverged and that RNR subclasses with inhibition mechanisms involving R1 oligomerization belong to a clade separated from the two subclasses forming R1-R2 octamers. These results give further insight into activity regulation in class I RNRs as an evolutionarily dynamic process.", "doi": "10.1074/jbc.RA120.014895", "pmid": "32883811", "labels": {"Protein Science Facility (PSF)": "Service", "Cryo-EM": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S0021-9258(17)50390-7"}, {"db": "pmc", "key": "PMC7667963"}, {"db": "PDB", "key": "2RCC"}, {"db": "PDB", "key": "6W4X"}, {"db": "PDB", "key": "5CNS"}], "notes": [], "created": "2020-10-03T13:43:28.482Z", "modified": "2024-01-16T13:48:41.347Z"}, {"entity": "publication", "iuid": "7b76865fb2364e6fa8946090ea425154", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7b76865fb2364e6fa8946090ea425154.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7b76865fb2364e6fa8946090ea425154"}}, "title": "The Immunology of Multisystem Inflammatory Syndrome in Children with COVID-19.", "authors": [{"family": "Consiglio", "given": "Camila Rosat", "initials": "CR", "orcid": "0000-0002-8901-2328", "researcher": {"href": "https://publications.scilifelab.se/researcher/7df7044aa718438ca370ed90cdd9c282.json"}}, {"family": "Cotugno", "given": "Nicola", "initials": "N", "orcid": "0000-0002-7748-1581", "researcher": {"href": "https://publications.scilifelab.se/researcher/56dc2dd7b83d4fbd9d20a008f89604da.json"}}, {"family": "Sardh", "given": "Fabian", "initials": "F"}, {"family": "Pou", "given": "Christian", "initials": "C"}, {"family": "Amodio", "given": "Donato", "initials": "D", "orcid": "0000-0003-4550-3018", "researcher": {"href": "https://publications.scilifelab.se/researcher/c1c02699a9564c09bff0a28036089857.json"}}, {"family": "Rodriguez", "given": "Lucie", "initials": "L", "orcid": "0000-0002-3692-9060", "researcher": {"href": "https://publications.scilifelab.se/researcher/1f9c2cfec48e4c4d8e9bc528a02d489b.json"}}, {"family": "Tan", "given": "Ziyang", "initials": "Z"}, {"family": "Zicari", "given": "Sonia", "initials": "S", "orcid": "0000-0003-1240-8057", "researcher": {"href": "https://publications.scilifelab.se/researcher/6721817c6fa143d69be06d7bcc960579.json"}}, {"family": "Ruggiero", "given": "Alessandra", "initials": "A", "orcid": "0000-0002-1041-7489", "researcher": {"href": "https://publications.scilifelab.se/researcher/7f80953fcc4f42fabfc21a70d6a39aba.json"}}, {"family": "Pascucci", "given": "Giuseppe Rubens", "initials": "GR", "orcid": "0000-0002-5978-1193", "researcher": {"href": "https://publications.scilifelab.se/researcher/27e5b15541cb4305aacfbcdc76e8070c.json"}}, {"family": "Santilli", "given": "Veronica", "initials": "V"}, {"family": "Campbell", "given": "Tessa", "initials": "T"}, {"family": "Bryceson", "given": "Yenan", "initials": "Y"}, {"family": "Eriksson", "given": "Daniel", "initials": "D"}, {"family": "Wang", "given": "Jun", "initials": "J"}, {"family": "Marchesi", "given": "Alessandra", "initials": "A"}, {"family": "Lakshmikanth", "given": "Tadepally", "initials": "T", "orcid": "0000-0001-7256-5770", "researcher": {"href": "https://publications.scilifelab.se/researcher/92e81aa6b0cf4ff0a18b14098bf0fcc1.json"}}, {"family": "Campana", "given": "Andrea", "initials": "A"}, {"family": "Villani", "given": "Alberto", "initials": "A", "orcid": "0000-0002-9120-0424", "researcher": {"href": "https://publications.scilifelab.se/researcher/4d74ddfe5709426783a3b9c753cacad3.json"}}, {"family": "Rossi", "given": "Paolo", "initials": "P"}, {"family": "CACTUS Study Team", "given": "", "initials": ""}, {"family": "Landegren", "given": "Nils", "initials": "N"}, {"family": "Palma", "given": "Paolo", "initials": "P", "orcid": "0000-0002-3066-4719", "researcher": {"href": "https://publications.scilifelab.se/researcher/275341cd978547cfa2aaf179cbd74011.json"}}, {"family": "Brodin", "given": "Petter", "initials": "P", "orcid": "0000-0002-8103-0046", "researcher": {"href": "https://publications.scilifelab.se/researcher/40097353cdb24e52bf2330eb687042bf.json"}}], "type": "journal article", "published": "2020-11-12", "journal": {"title": "Cell", "issn": "1097-4172", "issn-l": "0092-8674", "volume": "183", "issue": "4", "pages": "968-981.e7"}, "abstract": "Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is typically very mild and often asymptomatic in children. A complication is the rare multisystem inflammatory syndrome in children (MIS-C) associated with COVID-19, presenting 4-6 weeks after infection as high fever, organ dysfunction, and strongly elevated markers of inflammation. The pathogenesis is unclear but has overlapping features with Kawasaki disease suggestive of vasculitis and a likely autoimmune etiology. We apply systems-level analyses of blood immune cells, cytokines, and autoantibodies in healthy children, children with Kawasaki disease enrolled prior to COVID-19, children infected with SARS-CoV-2, and children presenting with MIS-C. We find that the inflammatory response in MIS-C differs from the cytokine storm of severe acute COVID-19, shares several features with Kawasaki disease, but also differs from this condition with respect to T cell subsets, interleukin (IL)-17A, and biomarkers associated with arterial damage. Finally, autoantibody profiling suggests multiple autoantibodies that could be involved in the pathogenesis of MIS-C.", "doi": "10.1016/j.cell.2020.09.016", "pmid": "32966765", "labels": {"Autoimmunity and Serology Profiling": "Service", "Affinity Proteomics Stockholm": "Service", "Cellular Immunomonitoring": "Technology development", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S0092-8674(20)31157-0"}, {"db": "pmc", "key": "PMC7474869"}], "notes": [], "created": "2020-09-07T21:59:50.131Z", "modified": "2024-01-16T13:48:41.355Z"}, {"entity": "publication", "iuid": "a6c74c26d13a4608b4806234c6d580d5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a6c74c26d13a4608b4806234c6d580d5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a6c74c26d13a4608b4806234c6d580d5"}}, "title": "Identification of Pre-Diagnostic Metabolic Patterns for Glioma Using Subset Analysis of Matched Repeated Time Points.", "authors": [{"family": "Jonsson", "given": "P\u00e4r", "initials": "P", "orcid": "0000-0001-8357-5018", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd630ff903db4a61af5bf65a46c9c098.json"}}, {"family": "Antti", "given": "Henrik", "initials": "H"}, {"family": "Sp\u00e4th", "given": "Florentin", "initials": "F"}, {"family": "Melin", "given": "Beatrice", "initials": "B"}, {"family": "Bj\u00f6rkblom", "given": "Benny", "initials": "B", "orcid": "0000-0001-9347-5790", "researcher": {"href": "https://publications.scilifelab.se/researcher/acf29b039dfc496fb33c0cf7cb1d587c.json"}}], "type": "journal article", "published": "2020-11-12", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "12", "issue": "11", "pages": "3349", "issn-l": "2072-6694"}, "abstract": "Here, we present a strategy for early molecular marker pattern detection-Subset analysis of Matched Repeated Time points (SMART)-used in a mass-spectrometry-based metabolomics study of repeated blood samples from future glioma patients and their matched controls. The outcome from SMART is a predictive time span when disease-related changes are detectable, defined by time to diagnosis and time between longitudinal sampling, and visualization of molecular marker patterns related to future disease. For glioma, we detect significant changes in metabolite levels as early as eight years before diagnosis, with longitudinal follow up within seven years. Elevated blood plasma levels of myo-inositol, cysteine, N-acetylglucosamine, creatinine, glycine, proline, erythronic-, 4-hydroxyphenylacetic-, uric-, and aceturic acid were particularly evident in glioma cases. We use data simulation to ensure non-random events and a separate data set for biomarker validation. The latent biomarker, consisting of 15 interlinked and significantly altered metabolites, shows a strong correlation to oxidative metabolism, glutathione biosynthesis and monosaccharide metabolism, linked to known early events in tumor development. This study highlights the benefits of progression pattern analysis and provide a tool for the discovery of early markers of disease.", "doi": "10.3390/cancers12113349", "pmid": "33198241", "labels": {"Bioinformatics Support for Computational Resources": "Service", "Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pii", "key": "cancers12113349"}, {"db": "pmc", "key": "PMC7696703"}], "notes": [], "created": "2020-12-11T12:04:50.936Z", "modified": "2025-10-17T13:03:16.601Z"}, {"entity": "publication", "iuid": "c9c5393783944aba9b33fbb25b673f2f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c9c5393783944aba9b33fbb25b673f2f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c9c5393783944aba9b33fbb25b673f2f"}}, "title": "Development and evaluation of a deep learning based artificial intelligence for automatic identification of gold fiducial markers in an MRI-only prostate radiotherapy workflow.", "authors": [{"family": "Gustafsson", "given": "Christian Jamtheim", "initials": "CJ", "orcid": "0000-0003-2931-5615", "researcher": {"href": "https://publications.scilifelab.se/researcher/f36744c1705a40b48bd3d65bb7653fd4.json"}}, {"family": "Sw\u00e4rd", "given": "Johan", "initials": "J"}, {"family": "Adalbj\u00f6rnsson", "given": "Stefan Ingi", "initials": "SI"}, {"family": "Jakobsson", "given": "Andreas", "initials": "A"}, {"family": "Olsson", "given": "Lars E", "initials": "LE"}], "type": "evaluation study", "published": "2020-11-12", "journal": {"title": "Phys Med Biol", "issn": "1361-6560", "issn-l": null, "volume": "65", "issue": "22", "pages": "225011"}, "abstract": "Identification of prostate gold fiducial markers in magnetic resonance imaging (MRI) images is challenging when CT images are not available, due to misclassifications from intra-prostatic calcifications. It is also a time consuming task and automated identification methods have been suggested as an improvement for both objectives. Multi-echo gradient echo (MEGRE) images have been utilized for manual fiducial identification with 100% detection accuracy. The aim is therefore to develop an automatic deep learning based method for fiducial identification in MRI images intended for MRI-only prostate radiotherapy. MEGRE images from 326 prostate cancer patients with fiducials were acquired on a 3T MRI, post-processed with N4 bias correction, and the fiducial center of mass (CoM) was identified. A 9 mm radius sphere was created around the CoM as ground truth. A deep learning HighRes3DNet model for semantic segmentation was trained using image augmentation. The model was applied to 39 MRI-only patients and 3D probability maps for fiducial location and segmentation were produced and spatially smoothed. In each of the three largest probability peaks, a 9 mm radius sphere was defined. Detection sensitivity and geometric accuracy was assessed. To raise awareness of potential false findings a 'BeAware' score was developed, calculated from the total number and quality of the probability peaks. All datasets, annotations and source code used were made publicly available. The detection sensitivity for all fiducials were 97.4%. Thirty-six out of thirty-nine patients had all fiducial markers correctly identified. All three failed patients generated a user notification using the BeAware score. The mean absolute difference between the detected fiducial and ground truth CoM was 0.7 \u00b1 0.9 [0 3.1] mm. A deep learning method for automatic fiducial identification in MRI images was developed and evaluated with state-of-the-art results. The BeAware score has the potential to notify the user regarding patients where the proposed method is uncertain.", "doi": "10.1088/1361-6560/abb0f9", "pmid": "33179610", "labels": {"AIDA Data Hub": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [], "notes": [], "created": "2021-11-10T16:59:47.048Z", "modified": "2023-05-25T15:53:04.029Z"}, {"entity": "publication", "iuid": "ba07627b1e2248a8a43555deaf34e3ba", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ba07627b1e2248a8a43555deaf34e3ba.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ba07627b1e2248a8a43555deaf34e3ba"}}, "title": "Association of aberrant ASNS imprinting with asparaginase sensitivity and chromosomal abnormality in childhood BCP-ALL.", "authors": [{"family": "Watanabe", "given": "Atsushi", "initials": "A", "orcid": "0000-0002-4181-8111", "researcher": {"href": "https://publications.scilifelab.se/researcher/665105919804451f904064e4a5d9b09f.json"}}, {"family": "Miyake", "given": "Kunio", "initials": "K", "orcid": "0000-0001-9196-2229", "researcher": {"href": "https://publications.scilifelab.se/researcher/a0c7fbd039fb4cb3bfac5060038111fb.json"}}, {"family": "Nordlund", "given": "Jessica", "initials": "J", "orcid": "0000-0001-8699-9959", "researcher": {"href": "https://publications.scilifelab.se/researcher/ddf48c9262134821bcc6ce1180049753.json"}}, {"family": "Syv\u00e4nen", "given": "Ann-Christine", "initials": "AC", "orcid": "0000-0002-9681-9146", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7012e35025543379380cb90efd71243.json"}}, {"family": "van der Weyden", "given": "Louise", "initials": "L", "orcid": "0000-0002-0645-1879", "researcher": {"href": "https://publications.scilifelab.se/researcher/ad8d71311de74b26bf7b706854478854.json"}}, {"family": "Honda", "given": "Hiroaki", "initials": "H"}, {"family": "Yamasaki", "given": "Norimasa", "initials": "N"}, {"family": "Nagamachi", "given": "Akiko", "initials": "A"}, {"family": "Inaba", "given": "Toshiya", "initials": "T", "orcid": "0000-0002-3455-6010", "researcher": {"href": "https://publications.scilifelab.se/researcher/9592ee7afe1d4969be71f057bfc9fb66.json"}}, {"family": "Ikawa", "given": "Tomokatsu", "initials": "T", "orcid": "0000-0001-9615-8889", "researcher": {"href": "https://publications.scilifelab.se/researcher/4c7ce37a92cb48fdbb2563ea23c64972.json"}}, {"family": "Urayama", "given": "Kevin Y", "initials": "KY"}, {"family": "Kiyokawa", "given": "Nobutaka", "initials": "N"}, {"family": "Ohara", "given": "Akira", "initials": "A"}, {"family": "Kimura", "given": "Shunsuke", "initials": "S", "orcid": "0000-0002-2158-467X", "researcher": {"href": "https://publications.scilifelab.se/researcher/04a614b852f740db90c696c0274dc814.json"}}, {"family": "Kubota", "given": "Yasuo", "initials": "Y", "orcid": "0000-0002-7909-5422", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d8c368135b047868a9cedf7142fbd8f.json"}}, {"family": "Takita", "given": "Junko", "initials": "J", "orcid": "0000-0002-2452-6520", "researcher": {"href": "https://publications.scilifelab.se/researcher/379d0df3460e400486fd6e4657bd8bf9.json"}}, {"family": "Goto", "given": "Hiroaki", "initials": "H"}, {"family": "Sakaguchi", "given": "Kimiyoshi", "initials": "K", "orcid": "0000-0002-3665-401X", "researcher": {"href": "https://publications.scilifelab.se/researcher/325662e23fc442c49edfe8bfb79f3aa5.json"}}, {"family": "Minegishi", "given": "Masayoshi", "initials": "M"}, {"family": "Iwamoto", "given": "Shotaro", "initials": "S"}, {"family": "Shinohara", "given": "Tamao", "initials": "T", "orcid": "0000-0003-0714-1239", "researcher": {"href": "https://publications.scilifelab.se/researcher/11d525e15d2940ad8eec61f3d9a88afe.json"}}, {"family": "Kagami", "given": "Keiko", "initials": "K"}, {"family": "Abe", "given": "Masako", "initials": "M"}, {"family": "Akahane", "given": "Koshi", "initials": "K", "orcid": "0000-0001-8591-1281", "researcher": {"href": "https://publications.scilifelab.se/researcher/d89f4af20f634416906fdc8d1554c91e.json"}}, {"family": "Goi", "given": "Kumiko", "initials": "K"}, {"family": "Sugita", "given": "Kanji", "initials": "K"}, {"family": "Inukai", "given": "Takeshi", "initials": "T"}], "type": "journal article", "published": "2020-11-12", "journal": {"title": "Blood", "issn": "1528-0020", "volume": "136", "issue": "20", "pages": "2319-2333", "issn-l": "0006-4971"}, "abstract": "Karyotype is an important prognostic factor in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL), but the underlying pharmacogenomics remain unknown. Asparaginase is an integral component in current chemotherapy for childhood BCP-ALL. Asparaginase therapy depletes serum asparagine. Normal hematopoietic cells can produce asparagine by asparagine synthetase (ASNS) activity, but ALL cells are unable to synthesize adequate amounts of asparagine. The ASNS gene has a typical CpG island in its promoter. Thus, methylation of the ASNS CpG island could be one of the epigenetic mechanisms for ASNS gene silencing in BCP-ALL. To gain deep insights into the pharmacogenomics of asparaginase therapy, we investigated the association of ASNS methylation status with asparaginase sensitivity. The ASNS CpG island is largely unmethylated in normal hematopoietic cells, but it is allele-specifically methylated in BCP-ALL cells. The ASNS gene is located at 7q21, an evolutionally conserved imprinted gene cluster. ASNS methylation in childhood BCP-ALL is associated with an aberrant methylation of the imprinted gene cluster at 7q21. Aberrant methylation of mouse Asns and a syntenic imprinted gene cluster is also confirmed in leukemic spleen samples from ETV6-RUNX1 knockin mice. In 3 childhood BCP-ALL cohorts, ASNS is highly methylated in BCP-ALL patients with favorable karyotypes but is mostly unmethylated in BCP-ALL patients with poor prognostic karyotypes. Higher ASNS methylation is associated with higher L-asparaginase sensitivity in BCP-ALL through lower ASNS gene and protein expression levels. These observations demonstrate that silencing of the ASNS gene as a result of aberrant imprinting is a pharmacogenetic mechanism for the leukemia-specific activity of asparaginase therapy in BCP-ALL.", "doi": "10.1182/blood.2019004090", "pmid": "32573712", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S0006-4971(20)79932-5"}, {"db": "pmc", "key": "PMC7702480"}], "notes": [], "created": "2020-11-05T12:22:54.859Z", "modified": "2024-01-16T13:48:41.370Z"}, {"entity": "publication", "iuid": "ecde5defaf5b4cf9bfcd95fb462ff3b8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ecde5defaf5b4cf9bfcd95fb462ff3b8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ecde5defaf5b4cf9bfcd95fb462ff3b8"}}, "title": "Recurring urothelial carcinomas show genomic rearrangements incompatible with a direct relationship.", "authors": [{"family": "Marzouka", "given": "Nour-Al-Dain", "initials": "NA"}, {"family": "Lindgren", "given": "David", "initials": "D"}, {"family": "Eriksson", "given": "Pontus", "initials": "P"}, {"family": "Sj\u00f6dahl", "given": "Gottfrid", "initials": "G"}, {"family": "Bernardo", "given": "Carina", "initials": "C"}, {"family": "Liedberg", "given": "Fredrik", "initials": "F"}, {"family": "Axelson", "given": "H\u00e5kan", "initials": "H"}, {"family": "H\u00f6glund", "given": "Mattias", "initials": "M"}], "type": "journal article", "published": "2020-11-11", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "19539", "issn-l": "2045-2322"}, "abstract": "We used the fact that patients with non-muscle invasive bladder tumors show local recurrences and multiple tumors to study re-initiation of tumor growth from the same urothelium. By extensive genomic analyses we show that tumors from the same patient are clonal. We show that gross genomic chromosomal aberrations may be detected in one tumor, only to be undetected in a recurrent tumor. By analyses of incompatible changes i.e., genomic alterations that cannot be reversed, we show that almost all tumors from a single patient may show such changes, thus the tumors cannot have originated from each other. As recurring tumors share both genomic alterations and driver gene mutations, these must have been present in the urothelium in periods with no tumor growth. We present a model that includes a growing and evolving field of urothelial cells that occasionally, and locally, produce bursts of cellular growth leading to overt tumors.", "doi": "10.1038/s41598-020-75854-4", "pmid": "33177554", "labels": {"Clinical Genomics Lund": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-75854-4"}, {"db": "pmc", "key": "PMC7658206"}], "notes": [], "created": "2021-11-25T09:35:36.155Z", "modified": "2021-11-25T09:35:36.161Z"}, {"entity": "publication", "iuid": "2e4d96d8328443b0b3a16151c314efa5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2e4d96d8328443b0b3a16151c314efa5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2e4d96d8328443b0b3a16151c314efa5"}}, "title": "Metabolomics of Interstitial Fluid, Plasma and Urine in Patients with Arterial Hypertension: New Insights into the Underlying Mechanisms.", "authors": [{"family": "Chachaj", "given": "Angelika", "initials": "A", "orcid": "0000-0001-8087-8005", "researcher": {"href": "https://publications.scilifelab.se/researcher/9e8abfb66d2e45578144baa9cbfee9fc.json"}}, {"family": "Matkowski", "given": "Rafa\u0142", "initials": "R", "orcid": "0000-0002-1705-5097", "researcher": {"href": "https://publications.scilifelab.se/researcher/e86797f5093f4eda8753b17c034108e6.json"}}, {"family": "Gr\u00f6bner", "given": "Gerhard", "initials": "G", "orcid": "0000-0001-7380-8797", "researcher": {"href": "https://publications.scilifelab.se/researcher/85bd86ebc85d4653bc880bc9be25bc80.json"}}, {"family": "Szuba", "given": "Andrzej", "initials": "A", "orcid": "0000-0002-7555-6201", "researcher": {"href": "https://publications.scilifelab.se/researcher/f45f54a728204a209d6e622f8560e470.json"}}, {"family": "Dudka", "given": "Ilona", "initials": "I", "orcid": "0000-0002-0153-7278", "researcher": {"href": "https://publications.scilifelab.se/researcher/6a9e0f8a4a624a259c75718ad90a5626.json"}}], "type": "journal article", "published": "2020-11-11", "journal": {"title": "Diagnostics", "issn": "2075-4418", "volume": "10", "issue": "11", "pages": "936", "issn-l": "2075-4418"}, "abstract": "There is growing evidence that lymphatic system plays a pivotal role in the pathogenesis of hypertension. Here, for the first time, the metabolome of interstitial fluid is analyzed in patients with arterial hypertension. Due to ethical issues to obtain human interstitial fluid samples, this study included only oncological patients after axillary lymph node dissection (ALND). These patients were matched into hypertensive (n = 29) and normotensive (n = 35) groups with similar oncological status. Simultaneous evaluation of interstitial fluid, plasma, and urine was obtained by combining high-resolution proton nuclear magnetic resonance (1H NMR) spectroscopy with chemometric analysis. Orthogonal partial least squares discriminant analysis (OPLS-DA) provided a clear differentiation between the hypertension and normotensive group, with the discrimination visible in each biofluid. In interstitial fluid nine potential metabolomic biomarkers for hypertension could be identified (creatinine, proline, pyroglutamine, glycine, alanine, 1-methylhistidine, the lysyl group of albumin, threonine, lipids), seven distinct markers in plasma (creatinine, mannose, isobutyrate, glycine, alanine, lactate, acetate, ornithine), and seven respectively in urine (methylmalonate, citrulline, phenylacetylglycine, fumarate, citrate, 1-methylnicotinamide, trans-aconitate). Biomarkers in plasma and urine allowed for the identification of specific biochemical pathways involved in hypertension, as previously suggested. Analysis of the interstitial fluid metabolome provided additional biomarkers compared to plasma or urine. Those biomarkers reflected primarily alterations in the metabolism of lipids and amino acids, and indicated increased levels of oxidative stress/inflammation in patients with hypertension.", "doi": "10.3390/diagnostics10110936", "pmid": "33187152", "labels": {"Swedish NMR Centre": "Collaborative"}, "xrefs": [{"db": "pii", "key": "diagnostics10110936"}, {"db": "pmc", "key": "PMC7698256"}], "notes": [], "created": "2020-11-24T20:28:46.271Z", "modified": "2025-10-17T13:03:56.476Z"}, {"entity": "publication", "iuid": "38f9cf370fca43aea73e0146f2e1a8e6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/38f9cf370fca43aea73e0146f2e1a8e6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/38f9cf370fca43aea73e0146f2e1a8e6"}}, "title": "Genome-Scale Mapping Reveals Complex Regulatory Activities of RpoN in Yersinia pseudotuberculosis.", "authors": [{"family": "Mahmud", "given": "A K M Firoj", "initials": "AKMF"}, {"family": "Nilsson", "given": "Kristina", "initials": "K"}, {"family": "Fahlgren", "given": "Anna", "initials": "A"}, {"family": "Navais", "given": "Roberto", "initials": "R"}, {"family": "Choudhury", "given": "Rajdeep", "initials": "R"}, {"family": "Avican", "given": "Kemal", "initials": "K"}, {"family": "F\u00e4llman", "given": "Maria", "initials": "M", "orcid": "0000-0001-6874-6384", "researcher": {"href": "https://publications.scilifelab.se/researcher/cadcd4e3e63742e7b9cbbb74907bf9fc.json"}}], "type": "journal article", "published": "2020-11-10", "journal": {"title": "mSystems", "issn": "2379-5077", "volume": "5", "issue": "6", "pages": null, "issn-l": "2379-5077"}, "abstract": "RpoN, an alternative sigma factor commonly known as \u03c354, is implicated in persistent stages of Yersinia pseudotuberculosis infections in which genes associated with this regulator are upregulated. We here combined phenotypic and genomic assays to provide insight into its role and function in this pathogen. RpoN was found essential for Y. pseudotuberculosis virulence in mice, and in vitro functional assays showed that it controls biofilm formation and motility. Mapping genome-wide associations of Y. pseudotuberculosis RpoN using chromatin immunoprecipitation coupled with next-generation sequencing identified an RpoN binding motif located at 103 inter- and intragenic sites on both sense and antisense strands. Deletion of rpoN had a large impact on gene expression, including downregulation of genes encoding proteins involved in flagellar assembly, chemotaxis, and quorum sensing. There were also clear indications of cross talk with other sigma factors, together with indirect effects due to altered expression of other regulators. Matching differential gene expression with locations of the binding sites implicated around 130 genes or operons potentially activated or repressed by RpoN. Mutagenesis of selected intergenic binding sites confirmed both positive and negative regulatory effects of RpoN binding. Corresponding mutations of intragenic sense sites had less impact on associated gene expression. Surprisingly, mutating intragenic sites on the antisense strand commonly reduced expression of genes carried by the corresponding sense strand.IMPORTANCE The alternative sigma factor RpoN (\u03c354), which is widely distributed in eubacteria, has been implicated in controlling gene expression of importance for numerous functions including virulence. Proper responses to host environments are crucial for bacteria to establish infection, and regulatory mechanisms involved are therefore of high interest for development of future therapeutics. Little is known about the function of RpoN in the intestinal pathogen Y. pseudotuberculosis, and we therefore investigated its regulatory role in this pathogen. This regulator was indeed found to be critical for establishment of infection in mice, likely involving its requirement for motility and biofilm formation. The RpoN regulon involved both activating and suppressive effects on gene expression which could be confirmed with mutagenesis of identified binding sites. This is the first study of its kind of RpoN in Y. pseudotuberculosis, revealing complex regulation of gene expression involving both productive and silent effects of its binding to DNA, providing important information about RpoN regulation in enterobacteria.", "doi": "10.1128/mSystems.01006-20", "pmid": "33172972", "labels": {"Bioinformatics Long-term Support WABI": "Service", "Bioinformatics Support, Infrastructure and Training": "Service", "NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pii", "key": "5/6/e01006-20"}, {"db": "pmc", "key": "PMC7657599"}], "notes": [], "created": "2020-11-21T09:21:23.391Z", "modified": "2024-01-16T13:48:41.377Z"}, {"entity": "publication", "iuid": "a8fd622b15c7467f997c96de28f1a14e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a8fd622b15c7467f997c96de28f1a14e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a8fd622b15c7467f997c96de28f1a14e"}}, "title": "Targeted sequencing reveals the somatic mutation landscape in a Swedish breast cancer cohort.", "authors": [{"family": "Mathioudaki", "given": "Argyri", "initials": "A"}, {"family": "Ljungstr\u00f6m", "given": "Viktor", "initials": "V"}, {"family": "Melin", "given": "Malin", "initials": "M", "orcid": "0000-0002-6589-2375", "researcher": {"href": "https://publications.scilifelab.se/researcher/190c3991975c43ec952a81df72292c9a.json"}}, {"family": "Arendt", "given": "Maja Louise", "initials": "ML"}, {"family": "Nordin", "given": "Jessika", "initials": "J", "orcid": "0000-0002-8414-2190", "researcher": {"href": "https://publications.scilifelab.se/researcher/2603df7f3ff84e6980605b9e8eef4c2f.json"}}, {"family": "Karlsson", "given": "\u00c5sa", "initials": "\u00c5"}, {"family": "Mur\u00e9n", "given": "Eva", "initials": "E"}, {"family": "Saksena", "given": "Pushpa", "initials": "P"}, {"family": "Meadows", "given": "Jennifer R S", "initials": "JRS"}, {"family": "Marinescu", "given": "Voichita D", "initials": "VD"}, {"family": "Sj\u00f6blom", "given": "Tobias", "initials": "T", "orcid": "0000-0001-6668-4140", "researcher": {"href": "https://publications.scilifelab.se/researcher/909f00a5bf6e465f9ff560b12bcd863a.json"}}, {"family": "Lindblad-Toh", "given": "Kerstin", "initials": "K", "orcid": "0000-0001-8338-0253", "researcher": {"href": "https://publications.scilifelab.se/researcher/e0063145f7d6476f80ab42f94833f4cf.json"}}], "type": "journal article", "published": "2020-11-09", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "19304", "issn-l": "2045-2322"}, "abstract": "Breast cancer (BC) is a genetically heterogeneous disease with high prevalence in Northern Europe. However, there has been no detailed investigation into the Scandinavian somatic landscape. Here, in a homogeneous Swedish cohort, we describe the somatic events underlying BC, leveraging a targeted next-generation sequencing approach. We designed a 20.5 Mb array targeting coding and regulatory regions of genes with a known role in BC (n = 765). The selected genes were either from human BC studies (n = 294) or from within canine mammary tumor associated regions (n = 471). A set of predominantly estrogen receptor positive tumors (ER + 85%) and their normal tissue counterparts (n = 61) were sequenced to ~ 140 \u00d7 and 85 \u00d7 mean target coverage, respectively. MuTect2 and VarScan2 were employed to detect single nucleotide variants (SNVs) and copy number aberrations (CNAs), while MutSigCV (SNVs) and GISTIC (CNAs) algorithms estimated the significance of recurrent somatic events. The significantly mutated genes (q \u2264 0.01) were PIK3CA (28% of patients), TP53 (21%) and CDH1 (11%). However, histone modifying genes contained the largest number of variants (KMT2C and ARID1A, together 28%). Mutations in KMT2C were mutually exclusive with PI3KCA mutations (p \u2264 0. 001) and half of these affect the formation of a functional PHD domain. The tumor suppressor CDK10 was deleted in 80% of the cohort while the oncogene MDM4 was amplified. Mutational signature analyses pointed towards APOBEC deaminase activity (COSMIC signature 2) and DNA mismatch repair (COSMIC signature 6). We noticed two significantly distinct patterns related to patient age; TP53 being more mutated in the younger group (29% vs 9% of patients) and CDH23 mutations were absent from the older group. The increased somatic mutation prevalence in the histone modifying genes KMT2C and ARID1A distinguishes the Swedish cohort from previous studies. KMT2C regulates enhancer activation and assists tumor proliferation in a hormone-rich environment, possibly pointing to a role in ER + BC, especially in older cases. Finally, age of onset appears to affect the mutational landscape suggesting that a larger age-diverse population incorporating more molecular subtypes should be studied to elucidate the underlying mechanisms.", "doi": "10.1038/s41598-020-74580-1", "pmid": "33168853", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-74580-1"}, {"db": "pmc", "key": "PMC7653953"}], "notes": [], "created": "2020-12-08T23:29:22.318Z", "modified": "2024-01-16T13:48:41.384Z"}, {"entity": "publication", "iuid": "8278837d4b3745bab6470962fe1dc162", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8278837d4b3745bab6470962fe1dc162.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8278837d4b3745bab6470962fe1dc162"}}, "title": "Identification of candidate genetic variants and altered protein expression in neural stem and mature neural cells support altered microtubule function to be an essential component in bipolar disorder.", "authors": [{"family": "Truv\u00e9", "given": "Katarina", "initials": "K", "orcid": "0000-0002-2449-8283", "researcher": {"href": "https://publications.scilifelab.se/researcher/0c36d2ff5111435aa23416cdfc359b2d.json"}}, {"family": "Parris", "given": "Toshima Z", "initials": "TZ", "orcid": "0000-0003-0834-5540", "researcher": {"href": "https://publications.scilifelab.se/researcher/0d528a2bce6c40829c1a6fed69c9f9ef.json"}}, {"family": "Vizlin-Hodzic", "given": "Dzeneta", "initials": "D", "orcid": "0000-0002-9696-7982", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a86a4c8b32a4af8a90240d44504b32b.json"}}, {"family": "Salmela", "given": "Susanne", "initials": "S"}, {"family": "Berger", "given": "Evelin", "initials": "E"}, {"family": "\u00c5gren", "given": "Hans", "initials": "H", "orcid": "0000-0003-0847-6700", "researcher": {"href": "https://publications.scilifelab.se/researcher/51b06f6b0b8d48fcabe31e6eaf1a08ce.json"}}, {"family": "Funa", "given": "Keiko", "initials": "K"}], "type": "journal article", "published": "2020-11-09", "journal": {"title": "Transl Psychiatry", "issn": "2158-3188", "issn-l": "2158-3188", "volume": "10", "issue": "1", "pages": "390"}, "abstract": "Identification of causative genetic variants leading to the development of bipolar disorder (BD) could result in genetic tests that would facilitate diagnosis. A better understanding of affected genes and pathways is also necessary for targeting of genes that may improve treatment strategies. To date several susceptibility genes have been reported from genome-wide association studies (GWAS), but little is known about specific variants that affect disease development. Here, we performed quantitative proteomics and whole-genome sequencing (WGS). Quantitative proteomics revealed NLRP2 as the most significantly up-regulated protein in neural stem cells and mature neural cells obtained from BD-patient cell samples. These results are in concordance with our previously published transcriptome analysis. Furthermore, the levels of FEZ2 and CADM2 proteins were also significantly differentially expressed in BD compared to control derived cells. The levels of FEZ2 were significantly downregulated in neural stem cells (NSC) while CADM2 was significantly up-regulated in mature neuronal cell culture. Promising novel candidate mutations were identified in the ANK3, NEK3, NEK7, TUBB, ANKRD1, and BRD2 genes. A literature search of candidate variants and deregulated proteins revealed that there are several connections to microtubule function for the molecules putatively involved. Microtubule function in neurons is critical for axon structure and axonal transport. A functional dynamic microtubule is also needed for an advocate response to cellular and environmental stress. If microtubule dynamics is compromised by mutations, it could be followed by deregulated expression forming a possible explanation for the inherited vulnerability to stressful life events that have been proposed to trigger mood episodes in BD patients.", "doi": "10.1038/s41398-020-01056-1", "pmid": "33168801", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41398-020-01056-1"}, {"db": "pmc", "key": "PMC7652854"}], "notes": [], "created": "2020-12-07T16:38:26.771Z", "modified": "2024-01-16T13:48:41.392Z"}, {"entity": "publication", "iuid": "7d82542687dd4fccb7affffc780d00ec", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7d82542687dd4fccb7affffc780d00ec.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7d82542687dd4fccb7affffc780d00ec"}}, "title": "Lysine-specific demethylase 1A restricts ex vivo propagation of human HSCs and is a target of UM171.", "authors": [{"family": "Subramaniam", "given": "Agatheeswaran", "initials": "A", "orcid": "0000-0003-3966-3875", "researcher": {"href": "https://publications.scilifelab.se/researcher/5ccb1e6798b84f128c3143c8da8bd35a.json"}}, {"family": "\u017demaitis", "given": "Kristijonas", "initials": "K", "orcid": "0000-0002-4098-0184", "researcher": {"href": "https://publications.scilifelab.se/researcher/d122126ea9094e1ab3c83a2265175042.json"}}, {"family": "Talkhoncheh", "given": "Mehrnaz Safaee", "initials": "MS"}, {"family": "Yudovich", "given": "David", "initials": "D", "orcid": "0000-0002-6580-0637", "researcher": {"href": "https://publications.scilifelab.se/researcher/e88d5ea329514c1881c5be9d9ab14412.json"}}, {"family": "B\u00e4ckstr\u00f6m", "given": "Alexandra", "initials": "A", "orcid": "0000-0003-2926-4221", "researcher": {"href": "https://publications.scilifelab.se/researcher/8032ff5c71544155978bfc1c73b34848.json"}}, {"family": "Debnath", "given": "Shubhranshu", "initials": "S"}, {"family": "Chen", "given": "Jun", "initials": "J", "orcid": "0000-0001-8516-0975", "researcher": {"href": "https://publications.scilifelab.se/researcher/93cf6eaa8a61475789a772d30f29d2e5.json"}}, {"family": "Jain", "given": "Mayur Vilas", "initials": "MV"}, {"family": "Galeev", "given": "Roman", "initials": "R"}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}, {"family": "Larsson", "given": "Jonas", "initials": "J"}], "type": "journal article", "published": "2020-11-05", "journal": {"title": "Blood", "issn": "1528-0020", "issn-l": "0006-4971", "volume": "136", "issue": "19", "pages": "2151-2161"}, "abstract": "Culture conditions in which hematopoietic stem cells (HSCs) can be expanded for clinical benefit are highly sought after. Here, we report that inhibition of the epigenetic regulator lysine-specific histone demethylase 1A (LSD1) induces a rapid expansion of human cord blood-derived CD34+ cells and promotes in vitro propagation of long-term repopulating HSCs by preventing differentiation. The phenotype and molecular characteristics of cells treated with LSD1 inhibitors were highly similar to cells treated with UM171, an agent promoting expansion of HSCs through undefined mechanisms and currently being tested in clinical trials. Strikingly, we found that LSD1, as well as other members of the LSD1-containing chromatin remodeling complex CoREST, is rapidly polyubiquitinated and degraded upon UM171 treatment. CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 depletion of the CoREST core member, RCOR1, resulted in expansion of CD34+ cells similar to LSD1 inhibition and UM171. Taken together, LSD1 and CoREST restrict HSC expansion and are principal targets of UM171, forming a mechanistic basis for the HSC-promoting activity of UM171.", "doi": "10.1182/blood.2020005827", "pmid": "32582923", "labels": {"Chemical Proteomics": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S0006-4971(21)00492-4"}, {"db": "pmc", "key": "PMC7645986"}], "notes": [], "created": "2020-07-01T11:45:41.535Z", "modified": "2024-01-18T23:37:23.868Z"}, {"entity": "publication", "iuid": "e572bce7ac984e7ea1ff903fed9a1293", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e572bce7ac984e7ea1ff903fed9a1293.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e572bce7ac984e7ea1ff903fed9a1293"}}, "title": "Draft Genome Assembly of the Freshwater Apex Predator Wels Catfish (Silurus glanis) Using Linked-Read Sequencing.", "authors": [{"family": "Ozerov", "given": "Mikhail Yu", "initials": "MY", "orcid": "0000-0002-1817-7707", "researcher": {"href": "https://publications.scilifelab.se/researcher/952f3c17dea44942be07ff8d52cf59c0.json"}}, {"family": "Flaj\u0161hans", "given": "Martin", "initials": "M", "orcid": "0000-0002-0357-5788", "researcher": {"href": "https://publications.scilifelab.se/researcher/d53be81465624a1cb6d3f47d3b1b9b40.json"}}, {"family": "Noreikiene", "given": "Kristina", "initials": "K", "orcid": "0000-0001-7529-4902", "researcher": {"href": "https://publications.scilifelab.se/researcher/2ac9138a3a55468e99283202735f7489.json"}}, {"family": "Vasem\u00e4gi", "given": "Anti", "initials": "A", "orcid": "0000-0002-2184-5534", "researcher": {"href": "https://publications.scilifelab.se/researcher/ad9186f5720d493980b92869fb504cb8.json"}}, {"family": "Gross", "given": "Riho", "initials": "R", "orcid": "0000-0003-0311-3003", "researcher": {"href": "https://publications.scilifelab.se/researcher/6d4530137e284124a79fd721f567703f.json"}}], "type": "journal article", "published": "2020-11-05", "journal": {"title": "G3 (Bethesda)", "issn": "2160-1836", "volume": "10", "issue": "11", "pages": "3897-3906", "issn-l": "2160-1836"}, "abstract": "The wels catfish (Silurus glanis) is one of the largest freshwater fish species in the world. This top predator plays a key role in ecosystem stability, and represents an iconic trophy-fish for recreational fishermen. S. glanis is also a highly valued species for its high-quality boneless flesh, and has been cultivated for over 100 years in Eastern and Central Europe. The interest in rearing S. glanis continues to grow; the aquaculture production of this species has almost doubled during the last decade. However, despite its high ecological, cultural and economic importance, the available genomic resources for S. glanis are very limited. To fulfill this gap we report a de novo assembly and annotation of the whole genome sequence of a female S. glanis The linked-read based technology with 10X Genomics Chromium chemistry and Supernova assembler produced a highly continuous draft genome of S. glanis: \u223c0.8Gb assembly (scaffold N 50 = 3.2 Mb; longest individual scaffold = 13.9 Mb; BUSCO completeness = 84.2%), which included 313.3 Mb of putative repeated sequences. In total, 21,316 protein-coding genes were predicted, of which 96% were annotated functionally from either sequence homology or protein signature searches. The highly continuous genome assembly will be an invaluable resource for aquaculture genomics, genetics, conservation, and breeding research of S. glanis.", "doi": "10.1534/g3.120.401711", "pmid": "32917720", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "g3.120.401711"}, {"db": "pmc", "key": "PMC7642921"}], "notes": [], "created": "2020-11-16T09:14:08.125Z", "modified": "2024-01-16T13:48:41.407Z"}, {"entity": "publication", "iuid": "c17b9b7db31141acabb6533bf3d03b4f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c17b9b7db31141acabb6533bf3d03b4f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c17b9b7db31141acabb6533bf3d03b4f"}}, "title": "DNA-Based Methods for Measurable Residual Disease Detection in NPM1-Mutated Acute Myeloid Leukemia; Establishment of Cut-Offs for qPCR, Digital Droplet PCR and Targeted Deep Sequencing", "authors": [{"family": "Pettersson", "given": "Louise", "initials": "L"}, {"family": "Johansson Alm", "given": "Sofie", "initials": "S"}, {"family": "Almstedt", "given": "Alvar", "initials": "A"}, {"family": "Lazarevic", "given": "Vladimir", "initials": "V"}, {"family": "Orrsj\u00f6", "given": "Gustav", "initials": "G"}, {"family": "Shah-Barkhordar", "given": "Giti", "initials": "G"}, {"family": "Fogelstrand", "given": "Linda", "initials": "L"}, {"family": "Ehinger", "given": "Mats", "initials": "M"}], "type": "journal-article", "published": "2020-11-05", "journal": {"title": "Blood", "issn": "0006-4971", "issn-l": null, "volume": "136", "issue": "Supplement 1", "pages": "6-6"}, "abstract": null, "doi": "10.1182/blood-2020-138675", "pmid": null, "labels": {"Clinical Genomics Gothenburg": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [], "notes": [], "created": "2022-03-29T13:38:00.810Z", "modified": "2022-11-21T15:37:05.661Z"}, {"entity": "publication", "iuid": "5c4e7cd6c6ad47f5bd1054cafd7408a0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5c4e7cd6c6ad47f5bd1054cafd7408a0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5c4e7cd6c6ad47f5bd1054cafd7408a0"}}, "title": "Point-of-Care Approaches for Meningitis Diagnosis in a Low-Resource Setting (Southwestern Uganda): Observational Cohort Study Protocol of the \"PI-POC\" Trial.", "authors": [{"family": "Gaudenzi", "given": "Giulia", "initials": "G", "orcid": "0000-0003-4923-6965", "researcher": {"href": "https://publications.scilifelab.se/researcher/ba29165719cb46eba1a62c4c3e9cb232.json"}}, {"family": "Kumbakumba", "given": "Elias", "initials": "E", "orcid": "0000-0001-7206-0609", "researcher": {"href": "https://publications.scilifelab.se/researcher/8395ba3e303747e4ba9cb03c2ce8ef2c.json"}}, {"family": "Rasti", "given": "Reza", "initials": "R", "orcid": "0000-0001-7816-8338", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e28ed799ee044f89513d9bd672e64d9.json"}}, {"family": "Nanjebe", "given": "Deborah", "initials": "D", "orcid": "0000-0002-5440-7100", "researcher": {"href": "https://publications.scilifelab.se/researcher/e436dca4c9844756b2b13205a106296b.json"}}, {"family": "R\u00e9u", "given": "Pedro", "initials": "P", "orcid": "0000-0001-7454-7189", "researcher": {"href": "https://publications.scilifelab.se/researcher/8c6e427a91df4b13b68be281692efc68.json"}}, {"family": "Nyehangane", "given": "Dan", "initials": "D", "orcid": "0000-0002-1898-4162", "researcher": {"href": "https://publications.scilifelab.se/researcher/91b877a3dd1a42828a6133484ef66865.json"}}, {"family": "M\u00e5rtensson", "given": "Andreas", "initials": "A", "orcid": "0000-0001-7504-8365", "researcher": {"href": "https://publications.scilifelab.se/researcher/3a064d85bb8d4da6a4e036fb887da577.json"}}, {"family": "Nassejje", "given": "Milly", "initials": "M", "orcid": "0000-0002-9964-1814", "researcher": {"href": "https://publications.scilifelab.se/researcher/c30c51e8624b45169c006d6617345a21.json"}}, {"family": "Karlsson", "given": "Jens", "initials": "J", "orcid": "0000-0002-8005-9197", "researcher": {"href": "https://publications.scilifelab.se/researcher/a35fef42c1e04345a6a60557f3b770c6.json"}}, {"family": "Mzee", "given": "John", "initials": "J", "orcid": "0000-0002-9932-6953", "researcher": {"href": "https://publications.scilifelab.se/researcher/e4bbfae70cab440da6a098fed5b6b388.json"}}, {"family": "Nilsson", "given": "Peter", "initials": "P", "orcid": "0000-0002-4657-8532", "researcher": {"href": "https://publications.scilifelab.se/researcher/799bcf1cf8cf451296f4535dd4ca9dc0.json"}}, {"family": "Businge", "given": "Stephen", "initials": "S", "orcid": "0000-0002-7094-1178", "researcher": {"href": "https://publications.scilifelab.se/researcher/949fae87c1124e9a8cfbf67f91397b05.json"}}, {"family": "Loh", "given": "Edmund", "initials": "E", "orcid": "0000-0001-7050-566X", "researcher": {"href": "https://publications.scilifelab.se/researcher/89e1fa0e881641c3999c556090a66a90.json"}}, {"family": "Boum Ii", "given": "Yap", "initials": "Y", "orcid": "0000-0002-6823-8539", "researcher": {"href": "https://publications.scilifelab.se/researcher/76ff1244bc9e4a7fb99b821c3598473e.json"}}, {"family": "Andersson-Svahn", "given": "Helene", "initials": "H", "orcid": "0000-0003-3409-276X", "researcher": {"href": "https://publications.scilifelab.se/researcher/608c083d9f924fdd9f3f4948d498f64e.json"}}, {"family": "Gantelius", "given": "Jesper", "initials": "J", "orcid": "0000-0002-2581-1542", "researcher": {"href": "https://publications.scilifelab.se/researcher/bbb1b41e117142d18c0730183dc6eb28.json"}}, {"family": "Mwanga-Amumpaire", "given": "Juliet", "initials": "J", "orcid": "0000-0002-6738-477X", "researcher": {"href": "https://publications.scilifelab.se/researcher/c024f8147ab94837b2344ce9aae0d92b.json"}}, {"family": "Alfv\u00e9n", "given": "Tobias", "initials": "T", "orcid": "0000-0002-2328-3512", "researcher": {"href": "https://publications.scilifelab.se/researcher/d808542ea67e466bbc93802c57574b8c.json"}}], "type": "journal article", "published": "2020-11-04", "journal": {"title": "JMIR Res Protoc", "issn": "1929-0748", "volume": "9", "issue": "11", "pages": "e21430", "issn-l": null}, "abstract": "A timely differential diagnostic is essential to identify the etiology of central nervous system (CNS) infections in children, in order to facilitate targeted treatment, manage patients, and improve clinical outcome.\n\nThe Pediatric Infection-Point-of-Care (PI-POC) trial is investigating novel methods to improve and strengthen the differential diagnostics of suspected childhood CNS infections in low-income health systems such as those in Southwestern Uganda. This will be achieved by evaluating (1) a novel DNA-based diagnostic assay for CNS infections, (2) a commercially available multiplex PCR-based meningitis/encephalitis (ME) panel for clinical use in a facility-limited laboratory setting, (3) proteomics profiling of blood from children with severe CNS infection as compared to outpatient controls with fever yet not severely ill, and (4) Myxovirus resistance protein A (MxA) as a biomarker in blood for viral CNS infection. Further changes in the etiology of childhood CNS infections after the introduction of the pneumococcal conjugate vaccine against Streptococcus pneumoniae will be investigated. In addition, the carriage and invasive rate of Neisseria meningitidis will be recorded and serotyped, and the expression of its major virulence factor (polysaccharide capsule) will be investigated.\n\nThe PI-POC trial is a prospective observational study of children including newborns up to 12 years of age with clinical features of CNS infection, and age-/sex-matched outpatient controls with fever yet not severely ill. Participants are recruited at 2 Pediatric clinics in Mbarara, Uganda. Cerebrospinal fluid (for cases only), blood, and nasopharyngeal (NP) swabs (for both cases and controls) sampled at both clinics are analyzed at the Epicentre Research Laboratory through gold-standard methods for CNS infection diagnosis (microscopy, biochemistry, and culture) and a commercially available ME panel for multiplex PCR analyses of the cerebrospinal fluid. An additional blood sample from cases is collected on day 3 after admission. After initial clinical analyses in Mbarara, samples will be transported to Stockholm, Sweden for (1) validation analyses of a novel nucleic acid-based POC test, (2) biomarker research, and (3) serotyping and molecular characterization of S. pneumoniae and N. meningitidis.\n\nA pilot study was performed from January to April 2019. The PI-POC trial enrollment of patients begun in April 2019 and will continue until September 2020, to include up to 300 cases and controls. Preliminary results from the PI-POC study are expected by the end of 2020.\n\nThe findings from the PI-POC study can potentially facilitate rapid etiological diagnosis of CNS infections in low-resource settings and allow for novel methods for determination of the severity of CNS infection in such environment.\n\nClinicalTrials.gov NCT03900091; https://clinicaltrials.gov/ct2/show/NCT03900091.\n\nDERR1-10.2196/21430.", "doi": "10.2196/21430", "pmid": "33146628", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service"}, "xrefs": [{"db": "pii", "key": "v9i11e21430"}, {"db": "pmc", "key": "PMC7690656"}, {"db": "ClinicalTrials.gov", "key": "NCT03900091"}], "notes": [], "created": "2020-12-07T16:38:28.050Z", "modified": "2021-11-10T12:45:31.567Z"}, {"entity": "publication", "iuid": "4f514cb335654c83b21a09ae787311a1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4f514cb335654c83b21a09ae787311a1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4f514cb335654c83b21a09ae787311a1"}}, "title": "MYC as a driver of stochastic chromatin networks: implications for the fitness of cancer cells.", "authors": [{"family": "Sumida", "given": "Noriyuki", "initials": "N", "orcid": "0000-0001-6121-4553", "researcher": {"href": "https://publications.scilifelab.se/researcher/82465febc13c4629b1ea5aa7e0b509c8.json"}}, {"family": "Sifakis", "given": "Emmanouil G", "initials": "EG", "orcid": "0000-0001-9919-4471", "researcher": {"href": "https://publications.scilifelab.se/researcher/c8506000a14a4a5286aa557ab67ef690.json"}}, {"family": "Kiani", "given": "Narsis A", "initials": "NA"}, {"family": "Ronnegren", "given": "Anna Lewandowska", "initials": "AL"}, {"family": "Scholz", "given": "Barbara A", "initials": "BA"}, {"family": "Vestlund", "given": "Johanna", "initials": "J"}, {"family": "Gomez-Cabrero", "given": "David", "initials": "D"}, {"family": "Tegner", "given": "Jesper", "initials": "J"}, {"family": "G\u00f6nd\u00f6r", "given": "Anita", "initials": "A"}, {"family": "Ohlsson", "given": "Rolf", "initials": "R", "orcid": "0000-0001-7308-3300", "researcher": {"href": "https://publications.scilifelab.se/researcher/e5f1c0948c164764938b9c4bee768e35.json"}}], "type": "journal article", "published": "2020-11-04", "journal": {"title": "Nucleic Acids Res.", "issn": "1362-4962", "volume": "48", "issue": "19", "pages": "10867-10876", "issn-l": "0305-1048"}, "abstract": "The relationship between stochastic transcriptional bursts and dynamic 3D chromatin states is not well understood. Using an innovated, ultra-sensitive technique, we address here enigmatic features underlying the communications between MYC and its enhancers in relation to the transcriptional process. MYC thus interacts with its flanking enhancers in a mutually exclusive manner documenting that enhancer hubs impinging on MYC detected in large cell populations likely do not exist in single cells. Dynamic encounters with pathologically activated enhancers responsive to a range of environmental cues, involved <10% of active MYC alleles at any given time in colon cancer cells. Being the most central node of the chromatin network, MYC itself likely drives its communications with flanking enhancers, rather than vice versa. We submit that these features underlie an acquired ability of MYC to become dynamically activated in response to a diverse range of environmental cues encountered by the cell during the neoplastic process.", "doi": "10.1093/nar/gkaa817", "pmid": "33051686", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "5922798"}, {"db": "pmc", "key": "PMC7641766"}], "notes": [], "created": "2020-12-07T16:34:41.435Z", "modified": "2024-01-16T13:48:41.415Z"}, {"entity": "publication", "iuid": "207936006e674630a3c278932612d8b8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/207936006e674630a3c278932612d8b8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/207936006e674630a3c278932612d8b8"}}, "title": "Hybridization-based in situ sequencing (HybISS) for spatially resolved transcriptomics in human and mouse brain tissue.", "authors": [{"family": "Gyllborg", "given": "Daniel", "initials": "D", "orcid": "0000-0002-1429-6426", "researcher": {"href": "https://publications.scilifelab.se/researcher/a5c0db7c1c9b474b8726fbd44d530330.json"}}, {"family": "Langseth", "given": "Christoffer Mattsson", "initials": "CM"}, {"family": "Qian", "given": "Xiaoyan", "initials": "X"}, {"family": "Choi", "given": "Eunkyoung", "initials": "E"}, {"family": "Salas", "given": "Sergio Marco", "initials": "SM"}, {"family": "Hilscher", "given": "Markus M", "initials": "MM"}, {"family": "Lein", "given": "Ed S", "initials": "ES"}, {"family": "Nilsson", "given": "Mats", "initials": "M", "orcid": "0000-0001-9985-0387", "researcher": {"href": "https://publications.scilifelab.se/researcher/197cf8ba83ba430f9712b2f4d94dc3e5.json"}}], "type": "journal article", "published": "2020-11-04", "journal": {"title": "Nucleic Acids Res.", "issn": "1362-4962", "issn-l": "0305-1048", "volume": "48", "issue": "19", "pages": "e112"}, "abstract": "Visualization of the transcriptome in situ has proven to be a valuable tool in exploring single-cell RNA-sequencing data, providing an additional spatial dimension to investigate multiplexed gene expression, cell types, disease architecture or even data driven discoveries. In situ sequencing (ISS) method based on padlock probes and rolling circle amplification has been used to spatially resolve gene transcripts in tissue sections of various origins. Here, we describe the next iteration of ISS, HybISS, hybridization-based in situ sequencing. Modifications in probe design allows for a new barcoding system via sequence-by-hybridization chemistry for improved spatial detection of RNA transcripts. Due to the amplification of probes, amplicons can be visualized with standard epifluorescence microscopes for high-throughput efficiency and the new sequencing chemistry removes limitations bound by sequence-by-ligation chemistry of ISS. HybISS design allows for increased flexibility and multiplexing, increased signal-to-noise, all without compromising throughput efficiency of imaging large fields of view. Moreover, the current protocol is demonstrated to work on human brain tissue samples, a source that has proven to be difficult to work with image-based spatial analysis techniques. Overall, HybISS technology works as a targeted amplification detection method for improved spatial transcriptomic visualization, and importantly, with an ease of implementation.", "doi": "10.1093/nar/gkaa792", "pmid": "32990747", "labels": {"Bioinformatics Support for Computational Resources": "Service", "In Situ Sequencing": "Technology development"}, "xrefs": [{"db": "pii", "key": "5912821"}, {"db": "pmc", "key": "PMC7641728"}], "notes": [], "created": "2020-12-11T18:51:33.812Z", "modified": "2025-10-17T13:02:18.129Z"}, {"entity": "publication", "iuid": "50a7dfe154a54741bad9e00e32d6c6c5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/50a7dfe154a54741bad9e00e32d6c6c5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/50a7dfe154a54741bad9e00e32d6c6c5"}}, "title": "Evolution from adherent to suspension: systems biology of HEK293 cell line development.", "authors": [{"family": "Malm", "given": "Magdalena", "initials": "M"}, {"family": "Saghaleyni", "given": "Rasool", "initials": "R"}, {"family": "Lundqvist", "given": "Magnus", "initials": "M"}, {"family": "Giudici", "given": "Marco", "initials": "M"}, {"family": "Chotteau", "given": "Veronique", "initials": "V"}, {"family": "Field", "given": "Ray", "initials": "R"}, {"family": "Varley", "given": "Paul G", "initials": "PG"}, {"family": "Hatton", "given": "Diane", "initials": "D"}, {"family": "Grassi", "given": "Luigi", "initials": "L"}, {"family": "Svensson", "given": "Thomas", "initials": "T", "orcid": "0000-0002-9190-2979", "researcher": {"href": "https://publications.scilifelab.se/researcher/dc636683ece84dc4ac3e4d10df0c7a49.json"}}, {"family": "Nielsen", "given": "Jens", "initials": "J", "orcid": "0000-0002-9955-6003", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a596e289be4438a8a2653b1f25fea8b.json"}}, {"family": "Rockberg", "given": "Johan", "initials": "J"}], "type": "comparative study", "published": "2020-11-04", "journal": {"title": "Sci Rep", "issn": "2045-2322", "issn-l": "2045-2322", "volume": "10", "issue": "1", "pages": "18996"}, "abstract": "The need for new safe and efficacious therapies has led to an increased focus on biologics produced in mammalian cells. The human cell line HEK293 has bio-synthetic potential for human-like production attributes and is currently used for manufacturing of several therapeutic proteins and viral vectors. Despite the increased popularity of this strain we still have limited knowledge on the genetic composition of its derivatives. Here we present a genomic, transcriptomic and metabolic gene analysis of six of the most widely used HEK293 cell lines. Changes in gene copy and expression between industrial progeny cell lines and the original HEK293 were associated with cellular component organization, cell motility and cell adhesion. Changes in gene expression between adherent and suspension derivatives highlighted switching in cholesterol biosynthesis and expression of five key genes (RARG, ID1, ZIC1, LOX and DHRS3), a pattern validated in 63 human adherent or suspension cell lines of other origin.", "doi": "10.1038/s41598-020-76137-8", "pmid": "33149219", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Systems Biology": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-76137-8"}, {"db": "pmc", "key": "PMC7642379"}], "notes": [], "created": "2020-12-07T16:34:45.132Z", "modified": "2022-02-14T12:16:01.662Z"}, {"entity": "publication", "iuid": "a2b1311ee277443ca4d6f14652b535cb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a2b1311ee277443ca4d6f14652b535cb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a2b1311ee277443ca4d6f14652b535cb"}}, "title": "Naming the untouchable - environmental sequences and niche partitioning as taxonomical evidence in fungi.", "authors": [{"family": "Kalsoom Khan", "given": "Faheema", "initials": "F"}, {"family": "Kluting", "given": "Kerri", "initials": "K"}, {"family": "T\u00e5ngrot", "given": "Jeanette", "initials": "J"}, {"family": "Urbina", "given": "Hector", "initials": "H"}, {"family": "Ammunet", "given": "Tea", "initials": "T"}, {"family": "Eshghi Sahraei", "given": "Shadi", "initials": "S"}, {"family": "Ryd\u00e9n", "given": "Martin", "initials": "M"}, {"family": "Ryberg", "given": "Martin", "initials": "M"}, {"family": "Rosling", "given": "Anna", "initials": "A", "orcid": "0000-0002-7003-5941", "researcher": {"href": "https://publications.scilifelab.se/researcher/c4c4bbb9e6c343808e8fa9345b7c05b2.json"}}], "type": "journal article", "published": "2020-11-03", "journal": {"title": "IMA Fungus", "issn": "2210-6340", "volume": "11", "issue": "1", "pages": "23", "issn-l": null}, "abstract": "Due to their submerged and cryptic lifestyle, the vast majority of fungal species are difficult to observe and describe morphologically, and many remain known to science only from sequences detected in environmental samples. The lack of practices to delimit and name most fungal species is a staggering limitation to communication and interpretation of ecology and evolution in kingdom Fungi. Here, we use environmental sequence data as taxonomical evidence and combine phylogenetic and ecological data to generate and test species hypotheses in the class Archaeorhizomycetes (Taphrinomycotina, Ascomycota). Based on environmental amplicon sequencing from a well-studied Swedish pine forest podzol soil, we generate 68 distinct species hypotheses of Archaeorhizomycetes, of which two correspond to the only described species in the class. Nine of the species hypotheses represent 78% of the sequenced Archaeorhizomycetes community, and are supported by long read data that form the backbone for delimiting species hypothesis based on phylogenetic branch lengths.Soil fungal communities are shaped by environmental filtering and competitive exclusion so that closely related species are less likely to co-occur in a niche if adaptive traits are evolutionarily conserved. In soil profiles, distinct vertical horizons represent a testable niche dimension, and we found significantly differential distribution across samples for a well-supported pair of sister species hypotheses. Based on the combination of phylogenetic and ecological evidence, we identify two novel species for which we provide molecular diagnostics and propose names. While environmental sequences cannot be automatically translated to species, they can be used to generate phylogenetically distinct species hypotheses that can be further tested using sequences as ecological evidence. We conclude that in the case of abundantly and frequently observed species, environmental sequences can support species recognition in the absences of physical specimens, while rare taxa remain uncaptured at our sampling and sequencing intensity.", "doi": "10.1186/s43008-020-00045-9", "pmid": "33292867", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1186/s43008-020-00045-9"}, {"db": "pmc", "key": "PMC7607712"}], "notes": [], "created": "2020-11-11T15:11:33.579Z", "modified": "2024-01-16T13:48:41.430Z"}, {"entity": "publication", "iuid": "da5d0305f08e461393fa1eb8676813d0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/da5d0305f08e461393fa1eb8676813d0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/da5d0305f08e461393fa1eb8676813d0"}}, "title": "From Inquilines to Gall Inducers: Genomic Signature of a Life-Style Transition in Synergus Gall Wasps.", "authors": [{"family": "Gobbo", "given": "Erik", "initials": "E", "orcid": "0000-0001-9897-8610", "researcher": {"href": "https://publications.scilifelab.se/researcher/107736ba83dc4131b9b1f2033ce85d18.json"}}, {"family": "Lartillot", "given": "Nicolas", "initials": "N"}, {"family": "Hearn", "given": "Jack", "initials": "J", "orcid": "0000-0003-3358-4949", "researcher": {"href": "https://publications.scilifelab.se/researcher/6fac223647864b76a5a7783ed7c19138.json"}}, {"family": "Stone", "given": "Graham N", "initials": "GN"}, {"family": "Abe", "given": "Yoshihisa", "initials": "Y"}, {"family": "Wheat", "given": "Christopher W", "initials": "CW"}, {"family": "Ide", "given": "Tatsuya", "initials": "T"}, {"family": "Ronquist", "given": "Fredrik", "initials": "F"}], "type": "comparative study", "published": "2020-11-03", "journal": {"title": "Genome Biol Evol", "issn": "1759-6653", "volume": "12", "issue": "11", "pages": "2060-2073", "issn-l": "1759-6653"}, "abstract": "Gall wasps (Hymenoptera: Cynipidae) induce complex galls on oaks, roses, and other plants, but the mechanism of gall induction is still unknown. Here, we take a comparative genomic approach to revealing the genetic basis of gall induction. We focus on Synergus itoensis, a species that induces galls inside oak acorns. Previous studies suggested that this species evolved the ability to initiate gall formation recently, as it is deeply nested within the genus Synergus, whose members are mostly inquilines that develop inside the galls of other species. We compared the genome of S. itoensis with that of three related Synergus inquilines to identify genomic changes associated with the origin of gall induction. We used a novel Bayesian selection analysis, which accounts for branch-specific and gene-specific selection effects, to search for signatures of selection in 7,600 single-copy orthologous genes shared by the four Synergus species. We found that the terminal branch leading to S. itoensis had more genes with a significantly elevated dN/dS ratio (positive signature genes) than the other terminal branches in the tree; the S. itoensis branch also had more genes with a significantly decreased dN/dS ratio. Gene set enrichment analysis showed that the positive signature gene set of S. itoensis, unlike those of the inquiline species, is enriched in several biological process Gene Ontology terms, the most prominent of which is \"Ovarian Follicle Cell Development.\" Our results indicate that the origin of gall induction is associated with distinct genomic changes, and provide a good starting point for further characterization of the genes involved.", "doi": "10.1093/gbe/evaa204", "pmid": "32986797", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "5912529"}, {"db": "pmc", "key": "PMC7674688"}], "notes": [], "created": "2020-12-07T16:28:56.741Z", "modified": "2024-01-16T13:48:41.438Z"}, {"entity": "publication", "iuid": "be8683efc0a64acdb85f7cc62d3c2801", "links": {"self": {"href": "https://publications.scilifelab.se/publication/be8683efc0a64acdb85f7cc62d3c2801.json"}, "display": {"href": "https://publications.scilifelab.se/publication/be8683efc0a64acdb85f7cc62d3c2801"}}, "title": "Cross-validated Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry Imaging Quantitation Protocol for a Pharmaceutical Drug and Its Drug-Target Effects in the Brain Using Time-of-Flight and Fourier Transform Ion Cyclotron Resonance Analyzers.", "authors": [{"family": "K\u00e4llback", "given": "Patrik", "initials": "P"}, {"family": "Vallianatou", "given": "Theodosia", "initials": "T"}, {"family": "Nilsson", "given": "Anna", "initials": "A"}, {"family": "Shariatgorji", "given": "Reza", "initials": "R", "orcid": "0000-0001-9484-0921", "researcher": {"href": "https://publications.scilifelab.se/researcher/7762e9f6779c4780a4077c557eb7a3b6.json"}}, {"family": "Schintu", "given": "Nicoletta", "initials": "N"}, {"family": "Pereira", "given": "Marcela", "initials": "M"}, {"family": "Barr\u00e9", "given": "Florian", "initials": "F"}, {"family": "Wadensten", "given": "Henrik", "initials": "H"}, {"family": "Svenningsson", "given": "Per", "initials": "P"}, {"family": "Andr\u00e9n", "given": "Per E", "initials": "PE", "orcid": "0000-0002-4062-7743", "researcher": {"href": "https://publications.scilifelab.se/researcher/64f6381de42949db8d30b56b526f3e26.json"}}], "type": "journal article", "published": "2020-11-03", "journal": {"title": "Anal. Chem.", "issn": "1520-6882", "volume": "92", "issue": "21", "pages": "14676-14684", "issn-l": "0003-2700"}, "abstract": "Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is an established tool in drug development, which enables visualization of drugs and drug metabolites at spatial localizations in tissue sections from different organs. However, robust and accurate quantitation by MALDI-MSI still remains a challenge. We present a quantitative MALDI-MSI method using two instruments with different types of mass analyzers, i.e., time-of-flight (TOF) and Fourier transform ion cyclotron resonance (FTICR) MS, for mapping levels of the in vivo-administered drug citalopram, a selective serotonin reuptake inhibitor, in mouse brain tissue sections. Six different methods for applying calibration standards and an internal standard were evaluated. The optimized method was validated according to authorities' guidelines and requirements, including selectivity, accuracy, precision, recovery, calibration curve, sensitivity, reproducibility, and stability parameters. We showed that applying a dilution series of calibration standards followed by a homogeneously applied, stable, isotopically labeled standard for normalization and a matrix on top of the tissue section yielded similar results to those from the reference method using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The validation results were within specified limits and the brain concentrations for TOF MS (51.1 \u00b1 4.4 pmol/mg) and FTICR MS (56.9 \u00b1 6.0 pmol/mg) did not significantly differ from those of the cross-validated LC-MS/MS method (55.0 \u00b1 4.9 pmol/mg). The effect of in vivo citalopram administration on the serotonin neurotransmitter system was studied in the hippocampus, a brain region that is the principal target of the serotonergic afferents along with the limbic system, and it was shown that serotonin was significantly increased (2-fold), but its metabolite 5-hydroxyindoleacetic acid was not. This study makes a substantial step toward establishing MALDI-MSI as a fully quantitative validated method.", "doi": "10.1021/acs.analchem.0c03203", "pmid": "33086792", "labels": {"Spatial Mass Spectrometry": "Technology development"}, "xrefs": [{"db": "pmc", "key": "PMC7660593"}], "notes": [], "created": "2021-03-26T12:46:21.810Z", "modified": "2021-12-03T11:50:47.352Z"}, {"entity": "publication", "iuid": "0356d54a7a4c443ca3b5ba481e0ea20b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0356d54a7a4c443ca3b5ba481e0ea20b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0356d54a7a4c443ca3b5ba481e0ea20b"}}, "title": "Putative Epigenetic Biomarkers of Stress in Red Blood Cells of Chickens Reared Across Different Biomes.", "authors": [{"family": "P\u00e9rtille", "given": "F\u00e1bio", "initials": "F"}, {"family": "Ibelli", "given": "Adriana Mercia Guaratini", "initials": "AMG"}, {"family": "Sharif", "given": "Maj El", "initials": "ME"}, {"family": "Poleti", "given": "Mirele Daiana", "initials": "MD"}, {"family": "Fr\u00f6hlich", "given": "Anna Sophie", "initials": "AS"}, {"family": "Rezaei", "given": "Shiva", "initials": "S"}, {"family": "Ledur", "given": "M\u00f4nica Corr\u00eaa", "initials": "MC"}, {"family": "Jensen", "given": "Per", "initials": "P"}, {"family": "Guerrero-Bosagna", "given": "Carlos", "initials": "C"}, {"family": "Coutinho", "given": "Luiz Lehmann", "initials": "LL"}], "type": "journal article", "published": "2020-11-02", "journal": {"title": "Front Genet", "issn": "1664-8021", "issn-l": "1664-8021", "volume": "11", "issue": null, "pages": "508809"}, "abstract": "Production animals are constantly subjected to early adverse environmental conditions that influence the adult phenotype and produce epigenetic effects. CpG dinucleotide methylation in red blood cells (RBC) could be a useful epigenetic biomarker to identify animals subjected to chronic stress in the production environment. Here we compared a reduced fraction of the RBC methylome of chickens exposed to social isolation to non-exposed. These experiments were performed in two different locations: Brazil and Sweden. The aim was to identify stress-associated DNA methylation profiles in RBC across these populations, in spite of the variable conditions to which birds are exposed in each facility and their different lineages. Birds were increasingly exposed to a social isolation treatment, combined with food and water deprivation, at random periods of the day from weeks 1-4 after hatching. We then collected the RBC DNA from individuals and compared a reduced fraction of their methylome between the experimental groups using two bioinformatic approaches to identify differentially methylated regions (DMRs): one using fixed-size windows and another that preselected differential peaks with MACS2. Three levels of significance were used (P \u2264 0.05, P \u2264 0.005, and P \u2264 0.0005) to identify DMRs between experimental groups, which were then used for different analyses. With both of the approaches more DMRs reached the defined significance thresholds in BR individuals compared to SW. However, more DMRs had higher fold change values in SW compared to BR individuals. Interestingly, ChrZ was enriched above expectancy for the presence of DMRs. Additionally, when analyzing the locations of these DMRs in relation to the transcription starting site (TSS), we found three peaks with high DMR presence: 10 kb upstream, the TSS itself, and 20-40 kb downstream. Interestingly, these peaks had DMRs with a high presence (>50%) of specific transcription factor binding sites. Three overlapping DMRs were found between the BR and SW population using the most relaxed p-value (P \u2264 0.05). With the most stringent p-value (P \u2264 0.0005), we found 7 and 4 DMRs between treatments in the BR and SW populations, respectively. This study is the first approximation to identify epigenetic biomarkers of long-term exposure to stress in different lineages of production animals.", "doi": "10.3389/fgene.2020.508809", "pmid": "33240310", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7667380"}], "notes": [], "created": "2020-12-07T16:38:30.735Z", "modified": "2021-11-10T12:45:39.955Z"}, {"entity": "publication", "iuid": "a0dda33b98ee48789e7ac7a800a80bb5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a0dda33b98ee48789e7ac7a800a80bb5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a0dda33b98ee48789e7ac7a800a80bb5"}}, "title": "Pericyte dysfunction due to Shb gene deficiency increases B16F10 melanoma lung metastasis.", "authors": [{"family": "He", "given": "Qi", "initials": "Q"}, {"family": "Li", "given": "Xiujuan", "initials": "X"}, {"family": "He", "given": "Liqun", "initials": "L"}, {"family": "Li", "given": "Yousheng", "initials": "Y"}, {"family": "Betsholtz", "given": "Christer", "initials": "C"}, {"family": "Welsh", "given": "Michael", "initials": "M", "orcid": "0000-0002-5467-9755", "researcher": {"href": "https://publications.scilifelab.se/researcher/c01673aeb9be429c80da30d5407b2725.json"}}], "type": "journal article", "published": "2020-11-01", "journal": {"title": "Int. J. Cancer", "issn": "1097-0215", "volume": "147", "issue": "9", "pages": "2634-2644", "issn-l": "0020-7136"}, "abstract": "Intravasation, vascular dissemination and metastasis of malignant tumor cells require their passage through the vascular wall which is commonly composed of pericytes and endothelial cells. We currently decided to investigate the relative contribution of these cell types to B16F10 melanoma metastasis in mice using an experimental model of host Shb gene (Src homology 2 domain-containing protein B) inactivation. Conditional inactivation of Shb in endothelial cells using Cdh5-CreERt2 resulted in decreased tumor growth, reduced vascular leakage, increased hypoxia and no effect on pericyte coverage and lung metastasis. RNAseq of tumor endothelial cells from these mice revealed changes in cellular components such as adherens junctions and focal adhesions by gene ontology analysis that were in line with the observed effects on leakage and junction morphology. Conditional inactivation of Shb in pericytes using Pdgfrb-CreERt2 resulted in decreased pericyte coverage of small tumor vessels with lumen, increased leakage, aberrant platelet-derived growth factor receptor B (PDGFRB) signaling and a higher frequency of lung metastasis without concomitant effects on tumor growth or oxygenation. Flow cytometry failed to reveal immune cell alterations that could explain the metastatic phenotype in this genetic model of Shb deficiency. It is concluded that proper pericyte function plays a significant role in suppressing B16F10 lung metastasis.", "doi": "10.1002/ijc.33110", "pmid": "32441314", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [], "notes": [], "created": "2020-12-08T23:56:20.495Z", "modified": "2024-01-16T13:48:41.445Z"}, {"entity": "publication", "iuid": "2aa9ff1359ee40c7a2ddf6c07a828ecf", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2aa9ff1359ee40c7a2ddf6c07a828ecf.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2aa9ff1359ee40c7a2ddf6c07a828ecf"}}, "title": "Interspecific Gene Flow and the Evolution of Specialization in Black and White Rhinoceros.", "authors": [{"family": "Moodley", "given": "Yoshan", "initials": "Y", "orcid": "0000-0003-4216-2924", "researcher": {"href": "https://publications.scilifelab.se/researcher/1de66994605d4a809f28b04c8dcf91c6.json"}}, {"family": "Westbury", "given": "Michael V", "initials": "MV", "orcid": "0000-0003-0478-3930", "researcher": {"href": "https://publications.scilifelab.se/researcher/0c4a764072a0474abe4ca97c7b220676.json"}}, {"family": "Russo", "given": "Isa-Rita M", "initials": "IM"}, {"family": "Gopalakrishnan", "given": "Shyam", "initials": "S"}, {"family": "Rakotoarivelo", "given": "Andrinajoro", "initials": "A"}, {"family": "Olsen", "given": "Remi-Andre", "initials": "RA"}, {"family": "Prost", "given": "Stefan", "initials": "S", "orcid": "0000-0002-6229-3596", "researcher": {"href": "https://publications.scilifelab.se/researcher/809ba200bb864ec9abf0d0cad09c5a42.json"}}, {"family": "Tunstall", "given": "Tate", "initials": "T"}, {"family": "Ryder", "given": "Oliver A", "initials": "OA"}, {"family": "Dal\u00e9n", "given": "Love", "initials": "L", "orcid": "0000-0001-8270-7613", "researcher": {"href": "https://publications.scilifelab.se/researcher/48ecf726779249ac9d12f4f7a1cc62bf.json"}}, {"family": "Bruford", "given": "Michael W", "initials": "MW"}], "type": "journal article", "published": "2020-11-01", "journal": {"volume": "37", "issn": "1537-1719", "issue": "11", "pages": "3105-3117", "title": "Mol. Biol. Evol.", "issn-l": "0737-4038"}, "abstract": "Africa's black (Diceros bicornis) and white (Ceratotherium simum) rhinoceros are closely related sister-taxa that evolved highly divergent obligate browsing and grazing feeding strategies. Although their precursor species Diceros praecox and Ceratotherium mauritanicum appear in the fossil record \u223c5.2 Ma, by 4 Ma both were still mixed feeders, and were even spatiotemporally sympatric at several Pliocene sites in what is today Africa's Rift Valley. Here, we ask whether or not D. praecox and C. mauritanicum were reproductively isolated when they came into Pliocene secondary contact. We sequenced and de novo assembled the first annotated black rhinoceros reference genome and compared it with available genomes of other black and white rhinoceros. We show that ancestral gene flow between D. praecox and C. mauritanicum ceased sometime between 3.3 and 4.1 Ma, despite conventional methods for the detection of gene flow from whole genome data returning false positive signatures of recent interspecific migration due to incomplete lineage sorting. We propose that ongoing Pliocene genetic exchange, for up to 2 My after initial divergence, could have potentially hindered the development of obligate feeding strategies until both species were fully reproductively isolated, but that the more severe and shifting paleoclimate of the early Pleistocene was likely the ultimate driver of ecological specialization in African rhinoceros.", "doi": "10.1093/molbev/msaa148", "pmid": "32585004", "labels": {"National Genomics Infrastructure": "Collaborative", "NGI Stockholm (Genomics Applications)": "Collaborative", "NGI Stockholm (Genomics Production)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "5862640"}], "notes": [], "created": "2020-07-08T13:04:56.178Z", "modified": "2021-11-10T12:45:42.221Z"}, {"entity": "publication", "iuid": "b3a44e9303844b0e8fdb8f107fe28a22", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b3a44e9303844b0e8fdb8f107fe28a22.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b3a44e9303844b0e8fdb8f107fe28a22"}}, "title": "Genomic epidemiology of Neisseria gonorrhoeae elucidating the gonococcal antimicrobial resistance and lineages/sublineages across Brazil, 2015-16.", "authors": [{"family": "Golparian", "given": "Daniel", "initials": "D"}, {"family": "Bazzo", "given": "Maria Luiza", "initials": "ML"}, {"family": "Golfetto", "given": "Lisl\u00e9ia", "initials": "L"}, {"family": "Gaspar", "given": "Pamela Cristina", "initials": "PC"}, {"family": "Sch\u00f6rner", "given": "Marcos Andr\u00e9", "initials": "MA"}, {"family": "Schwartz Benzaken", "given": "Adele", "initials": "A"}, {"family": "Ramos", "given": "Mauro Cunha", "initials": "MC"}, {"family": "Ferreira", "given": "William Antunes", "initials": "WA"}, {"family": "Alonso Neto", "given": "Jos\u00e9 Boullosa", "initials": "JB"}, {"family": "Mendes Pereira", "given": "Gerson Fernando", "initials": "GF"}, {"family": "Unemo", "given": "Magnus", "initials": "M", "orcid": "0000-0003-1710-2081", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f1494bae3b140a3a8761092e420a5de.json"}}, {"family": "Brazilian-GASP Network", "given": "", "initials": ""}], "type": "journal article", "published": "2020-11-01", "journal": {"title": "J. Antimicrob. Chemother.", "issn": "1460-2091", "issn-l": "0305-7453", "volume": "75", "issue": "11", "pages": "3163-3172"}, "abstract": "Neisseria gonorrhoeae antimicrobial resistance (AMR) surveillance is imperative internationally, but only eight (22.9%) countries in the WHO Region of the Americas reported complete AMR data to the WHO Global Gonococcal Antimicrobial Surveillance Program (WHO GASP) in 2016. Genomic studies are ideal for enhanced understanding of gonococcal populations, including the spread of AMR strains. To elucidate the circulating gonococcal lineages/sublineages, including their AMR determinants, and the baseline genomic diversity among gonococcal strains in Brazil, we conducted WGS on 548 isolates obtained in 2015-16 across all five macroregions in Brazil.\r\n\r\nA total of 548 gonococcal isolates cultured across Brazil in 2015-16 were genome sequenced. AMR was determined using agar dilution and/or Etest. Genome sequences of isolates from Argentina (n = 158) and the 2016 WHO reference strains (n = 14) were included in the analysis.\r\n\r\nWe found 302, 68 and 214 different NG-MAST, MLST and NG-STAR STs, respectively. The phylogenomic analysis identified one main antimicrobial-susceptible lineage and one AMR lineage, which was divided into two sublineages with different AMR profiles. Determination of NG-STAR networks of clonal complexes was shown as a new and valuable molecular epidemiological analysis. Several novel mosaic mtrD (and mtrR and mtrE) variants associated with azithromycin resistance were identified.\r\n\r\nWe describe the first genomic baseline data to support the Brazilian GASP. The high prevalence of resistance to ciprofloxacin, tetracycline and benzylpenicillin, and the high number of isolates with mosaic penA and azithromycin resistance mutations, should prompt continued and strengthened AMR surveillance, including WGS, of N. gonorrhoeae in Brazil.", "doi": "10.1093/jac/dkaa318", "pmid": "32785692", "labels": {"Clinical Genomics \u00d6rebro": "Technology development", "Clinical Genomics": "Technology development"}, "xrefs": [{"db": "pii", "key": "5891806"}], "notes": [], "created": "2020-11-27T14:02:26.079Z", "modified": "2021-12-08T12:30:15.933Z"}, {"entity": "publication", "iuid": "2fcbe860666e49c1a3a45f5de295f491", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2fcbe860666e49c1a3a45f5de295f491.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2fcbe860666e49c1a3a45f5de295f491"}}, "title": "Angiotensin-converting enzyme 2 (ACE2) levels in relation to risk factors for COVID-19 in two large cohorts of patients with atrial fibrillation.", "authors": [{"family": "Wallentin", "given": "Lars", "initials": "L", "orcid": "0000-0003-0378-6531", "researcher": {"href": "https://publications.scilifelab.se/researcher/388a76db2e4d423882d1cf2bf6b7d985.json"}}, {"family": "Lindb\u00e4ck", "given": "Johan", "initials": "J", "orcid": "0000-0002-6473-8798", "researcher": {"href": "https://publications.scilifelab.se/researcher/3cea1044231d40b5a3bf186485d97cd4.json"}}, {"family": "Eriksson", "given": "Niclas", "initials": "N", "orcid": "0000-0002-2152-4343", "researcher": {"href": "https://publications.scilifelab.se/researcher/64611a83caba46d597f45371b77de26b.json"}}, {"family": "Hijazi", "given": "Ziad", "initials": "Z"}, {"family": "Eikelboom", "given": "John W", "initials": "JW"}, {"family": "Ezekowitz", "given": "Michael D", "initials": "MD", "orcid": "0000-0003-3623-2252", "researcher": {"href": "https://publications.scilifelab.se/researcher/43f3a6f18de74bb6a632b1b16d1b778c.json"}}, {"family": "Granger", "given": "Christopher B", "initials": "CB"}, {"family": "Lopes", "given": "Renato D", "initials": "RD"}, {"family": "Yusuf", "given": "Salim", "initials": "S"}, {"family": "Oldgren", "given": "Jonas", "initials": "J", "orcid": "0000-0002-9969-3921", "researcher": {"href": "https://publications.scilifelab.se/researcher/14e1774fd1674edeaaa64a3f86d051d7.json"}}, {"family": "Siegbahn", "given": "Agneta", "initials": "A"}], "type": "journal article", "published": "2020-11-01", "journal": {"title": "Eur. Heart J.", "issn": "1522-9645", "volume": "41", "issue": "41", "pages": "4037-4046", "issn-l": "0195-668X"}, "abstract": "The global COVID-19 pandemic is caused by the SARS-CoV-2 virus entering human cells using angiotensin-converting enzyme 2 (ACE2) as a cell surface receptor. ACE2 is shed to the circulation, and a higher plasma level of soluble ACE2 (sACE2) might reflect a higher cellular expression of ACE2. The present study explored the associations between sACE2 and clinical factors, cardiovascular biomarkers, and genetic variability.\n\nPlasma and DNA samples were obtained from two international cohorts of elderly patients with atrial fibrillation (n = 3999 and n = 1088). The sACE2 protein level was measured by the Olink Proteomics\u00ae Multiplex CVD II96 \u00d7 96 panel. Levels of the biomarkers high-sensitive cardiac troponin T (hs-cTnT), N-terminal probrain natriuretic peptide (NT-proBNP), growth differentiation factor 15 (GDF-15), C-reactive protein, interleukin-6, D-dimer, and cystatin-C were determined by immunoassays. Genome-wide association studies were performed by Illumina chips. Higher levels of sACE2 were statistically significantly associated with male sex, cardiovascular disease, diabetes, and older age. The sACE2 level was most strongly associated with the levels of GDF-15, NT-proBNP, and hs-cTnT. When adjusting for these biomarkers, only male sex remained associated with sACE2. We found no statistically significant genetic regulation of the sACE2 level.\n\nMale sex and clinical or biomarker indicators of biological ageing, cardiovascular disease, and diabetes are associated with higher sACE2 levels. The levels of GDF-15 and NT-proBNP, which are associated both with the sACE2 level and a higher risk for mortality and cardiovascular disease, might contribute to better identification of risk for severe COVID-19 infection.", "doi": "10.1093/eurheartj/ehaa697", "pmid": "32984892", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "Affinity Proteomics Uppsala": "Service"}, "xrefs": [{"db": "pii", "key": "5912214"}, {"db": "pmc", "key": "PMC7543499"}, {"db": "ClinicalTrials.gov", "key": "NCT00262600"}, {"db": "ClinicalTrials.gov", "key": "NCT00412984"}], "notes": [], "created": "2020-10-20T06:59:27.289Z", "modified": "2021-12-10T09:29:55.907Z"}, {"entity": "publication", "iuid": "f4c47f02826749cbafe16bedd0a59d3b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f4c47f02826749cbafe16bedd0a59d3b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f4c47f02826749cbafe16bedd0a59d3b"}}, "title": "The proliferative history shapes the DNA methylome of B-cell tumors and predicts clinical outcome.", "authors": [{"family": "Duran-Ferrer", "given": "Mart\u00ed", "initials": "M", "orcid": "0000-0003-1666-5819", "researcher": {"href": "https://publications.scilifelab.se/researcher/00de5a3a802143d184c21e397fc9b3e3.json"}}, {"family": "Clot", "given": "Guillem", "initials": "G"}, {"family": "Nadeu", "given": "Ferran", "initials": "F", "orcid": "0000-0003-2910-9440", "researcher": {"href": "https://publications.scilifelab.se/researcher/d4654f6b3cd74ddfb4d859edff5fbc95.json"}}, {"family": "Beekman", "given": "Ren\u00e9e", "initials": "R"}, {"family": "Baumann", "given": "Tycho", "initials": "T"}, {"family": "Nordlund", "given": "Jessica", "initials": "J"}, {"family": "Marincevic-Zuniga", "given": "Yanara", "initials": "Y"}, {"family": "L\u00f6nnerholm", "given": "Gudmar", "initials": "G"}, {"family": "Rivas-Delgado", "given": "Alfredo", "initials": "A", "orcid": "0000-0003-0385-3415", "researcher": {"href": "https://publications.scilifelab.se/researcher/7fad7e4db089481582fbc48fe312b7c2.json"}}, {"family": "Mart\u00edn", "given": "Silvia", "initials": "S"}, {"family": "Ordo\u00f1ez", "given": "Raquel", "initials": "R"}, {"family": "Castellano", "given": "Giancarlo", "initials": "G"}, {"family": "Kulis", "given": "Marta", "initials": "M"}, {"family": "Queir\u00f3s", "given": "Ana C", "initials": "AC"}, {"family": "Lee", "given": "Seung-Tae", "initials": "S"}, {"family": "Wiemels", "given": "Joseph", "initials": "J"}, {"family": "Royo", "given": "Romina", "initials": "R"}, {"family": "Puiggr\u00f3s", "given": "Montserrat", "initials": "M", "orcid": "0000-0001-5034-7924", "researcher": {"href": "https://publications.scilifelab.se/researcher/c92c686a51b44dae85d15e867dc8a9b3.json"}}, {"family": "Lu", "given": "Junyan", "initials": "J"}, {"family": "Gin\u00e9", "given": "Eva", "initials": "E"}, {"family": "Be\u00e0", "given": "S\u00edlvia", "initials": "S"}, {"family": "Jares", "given": "Pedro", "initials": "P", "orcid": "0000-0002-8401-579X", "researcher": {"href": "https://publications.scilifelab.se/researcher/763b4efd77664b8aa47a70bb9a577b0f.json"}}, {"family": "Agirre", "given": "Xabier", "initials": "X", "orcid": "0000-0002-6558-9560", "researcher": {"href": "https://publications.scilifelab.se/researcher/4226533ab5484c698a0aa6471dabf848.json"}}, {"family": "Prosper", "given": "Felipe", "initials": "F"}, {"family": "L\u00f3pez-Ot\u00edn", "given": "Carlos", "initials": "C", "orcid": "0000-0001-6964-1904", "researcher": {"href": "https://publications.scilifelab.se/researcher/accdad365e904fd9a8b3c64dcaabbaf5.json"}}, {"family": "Puente", "given": "Xos\u00e9 S", "initials": "XS", "orcid": "0000-0001-9525-1483", "researcher": {"href": "https://publications.scilifelab.se/researcher/3c757bd329184ea2a2aa9183802fefb1.json"}}, {"family": "Oakes", "given": "Christopher C", "initials": "CC"}, {"family": "Zenz", "given": "Thorsten", "initials": "T", "orcid": "0000-0001-7890-9845", "researcher": {"href": "https://publications.scilifelab.se/researcher/8f6b107b1ec94de7bbc260f92f2dcc9f.json"}}, {"family": "Delgado", "given": "Julio", "initials": "J"}, {"family": "L\u00f3pez-Guillermo", "given": "Armando", "initials": "A"}, {"family": "Campo", "given": "El\u00edas", "initials": "E", "orcid": "0000-0001-9850-9793", "researcher": {"href": "https://publications.scilifelab.se/researcher/5642afaa4ed648dfabe66194e42bc01b.json"}}, {"family": "Mart\u00edn-Subero", "given": "Jos\u00e9 Ignacio", "initials": "JI", "orcid": "0000-0001-8809-5195", "researcher": {"href": "https://publications.scilifelab.se/researcher/06ccbd6b7051490fb2764ce9da7a418e.json"}}], "type": "journal article", "published": "2020-11-00", "journal": {"title": "Nat Cancer", "issn": "2662-1347", "issn-l": null, "volume": "1", "issue": "11", "pages": "1066-1081"}, "abstract": "We report a systematic analysis of the DNA methylation variability in 1,595 samples of normal cell subpopulations and 14 tumor subtypes spanning the entire human B-cell lineage. Differential methylation among tumor entities relates to differences in cellular origin and to de novo epigenetic alterations, which allowed us to build an accurate machine learning-based diagnostic algorithm. We identify extensive patient-specific methylation variability in silenced chromatin associated with the proliferative history of normal and neoplastic B cells. Mitotic activity generally leaves both hyper- and hypomethylation imprints, but some B-cell neoplasms preferentially gain or lose DNA methylation. Subsequently, we construct a DNA methylation-based mitotic clock called epiCMIT, whose lapse magnitude represents a strong independent prognostic variable in B-cell tumors and is associated with particular driver genetic alterations. Our findings reveal DNA methylation as a holistic tracer of B-cell tumor developmental history, with implications in the differential diagnosis and prediction of clinical outcome.", "doi": "10.1038/s43018-020-00131-2", "pmid": "34079956", "labels": {"NGI SNP genotyping": "Collaborative", "National Genomics Infrastructure": "Collaborative", "NGI Uppsala (SNP&SEQ Technology Platform)": "Collaborative"}, "xrefs": [{"db": "mid", "key": "NIHMS1700108"}, {"db": "pmc", "key": "PMC8168619"}, {"db": "pii", "key": "10.1038/s43018-020-00131-2"}], "notes": [], "created": "2023-01-03T14:47:04.559Z", "modified": "2023-01-03T14:53:28.577Z"}, {"entity": "publication", "iuid": "b8dd2d1744ce4b89a006f7ffdedaaf6d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b8dd2d1744ce4b89a006f7ffdedaaf6d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b8dd2d1744ce4b89a006f7ffdedaaf6d"}}, "title": "Sahelian pastoralism from the perspective of variants associated with lactase persistence.", "authors": [{"family": "Priehodov\u00e1", "given": "Edita", "initials": "E"}, {"family": "Austerlitz", "given": "Fr\u00e9d\u00e9ric", "initials": "F"}, {"family": "\u010c\u00ed\u017ekov\u00e1", "given": "Martina", "initials": "M"}, {"family": "Nov\u00e1\u010dkov\u00e1", "given": "Jana", "initials": "J"}, {"family": "Ricaut", "given": "Fran\u00e7ois-Xavier", "initials": "FX"}, {"family": "Hofmanov\u00e1", "given": "Zuzana", "initials": "Z"}, {"family": "Schlebusch", "given": "Carina M", "initials": "CM"}, {"family": "\u010cern\u00fd", "given": "Viktor", "initials": "V", "orcid": "0000-0003-1197-6634", "researcher": {"href": "https://publications.scilifelab.se/researcher/4eb871a8b08b461b9d308db875f4f8b9.json"}}], "type": "journal article", "published": "2020-11-00", "journal": {"title": "Am. J. Phys. Anthropol.", "issn": "1096-8644", "volume": "173", "issue": "3", "pages": "423-436", "issn-l": "0002-9483"}, "abstract": "Archeological evidence shows that first nomadic pastoralists came to the African Sahel from northeastern Sahara, where milking is reported by ~7.5 ka. A second wave of pastoralists arrived with the expansion of Arabic tribes in 7th-14th century CE. All Sahelian pastoralists depend on milk production but genetic diversity underlying their lactase persistence (LP) is poorly understood.\n\nWe investigated SNP variants associated with LP in 1,241 individuals from 29 mostly pastoralist populations in the Sahel. Then, we analyzed six SNPs in the neighboring fragment (419 kb) in the Fulani and Tuareg with the -13910*T mutation, reconstructed haplotypes, and calculated expansion age and growth rate of this variant.\n\nOur results reveal a geographic localization of two different LP variants in the Sahel: -13910*T west of Lake Chad (Fulani and Tuareg pastoralists) and -13915*G east of there (mostly Arabic-speaking pastoralists). We show that -13910*T has a more diversified haplotype background among the Fulani than among the Tuareg and that the age estimate for expansion of this variant among the Fulani (~8.5 ka) corresponds to introduction of cattle to the area.\n\nThis is the first study showing that the \"Eurasian\" LP allele -13910*T is widespread both in northern Europe and in the Sahel; however, it is limited to pastoralists in the Sahel. Since the Fulani haplotype with -13910*T is shared with contemporary Eurasians, its origin could be in a region encompassing the Near East and northeastern Africa in a population ancestral to both Saharan pastoralists and European farmers.", "doi": "10.1002/ajpa.24116", "pmid": "32812238", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [], "notes": [], "created": "2020-10-20T06:59:12.759Z", "modified": "2024-01-16T13:48:41.456Z"}, {"entity": "publication", "iuid": "1fcb59bfe89a4aa2bc5101cd706fe80f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1fcb59bfe89a4aa2bc5101cd706fe80f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1fcb59bfe89a4aa2bc5101cd706fe80f"}}, "title": "Optimized metabarcoding with Pacific biosciences enables semi-quantitative analysis of fungal communities.", "authors": [{"family": "Casta\u00f1o", "given": "Carles", "initials": "C", "orcid": "0000-0002-2403-7006", "researcher": {"href": "https://publications.scilifelab.se/researcher/b7bfa857714f425886c4484c15eb59a5.json"}}, {"family": "Berlin", "given": "Anna", "initials": "A", "orcid": "0000-0002-9518-5719", "researcher": {"href": "https://publications.scilifelab.se/researcher/023743c670cc408bb4ed767cb8ee558a.json"}}, {"family": "Brandstr\u00f6m Durling", "given": "Mikael", "initials": "M", "orcid": "0000-0001-6485-197X", "researcher": {"href": "https://publications.scilifelab.se/researcher/7be72d0dcc48489495509b23c7ad3d38.json"}}, {"family": "Ihrmark", "given": "Katharina", "initials": "K"}, {"family": "Lindahl", "given": "Bj\u00f6rn D", "initials": "BD", "orcid": "0000-0002-3384-4547", "researcher": {"href": "https://publications.scilifelab.se/researcher/b7a40688d33545a19c3c666940bda255.json"}}, {"family": "Stenlid", "given": "Jan", "initials": "J", "orcid": "0000-0002-5344-2094", "researcher": {"href": "https://publications.scilifelab.se/researcher/eac6fc31e38c4552a986310015fcb1b4.json"}}, {"family": "Clemmensen", "given": "Karina E", "initials": "KE", "orcid": "0000-0002-9627-6428", "researcher": {"href": "https://publications.scilifelab.se/researcher/73a4e19bdfc1431c9dd1c3f1cd58c766.json"}}, {"family": "Olson", "given": "\u00c5ke", "initials": "\u00c5", "orcid": "0000-0001-8998-6096", "researcher": {"href": "https://publications.scilifelab.se/researcher/83a79139c2b94d9f97cf038e1cab8c03.json"}}], "type": "journal article", "published": "2020-11-00", "journal": {"title": "New Phytol.", "issn": "1469-8137", "issn-l": "0028-646X", "volume": "228", "issue": "3", "pages": null}, "abstract": "Recent studies have questioned the use of high-throughput sequencing of the nuclear ribosomal internal transcribed spacer (ITS) region to derive a semi-quantitative representation of fungal community composition. However, comprehensive studies that quantify biases occurring during PCR and sequencing of ITS amplicons are still lacking. We used artificially assembled communities consisting of 10 ITS-like fragments of varying lengths and guanine-cytosine (GC) contents to evaluate and quantify biases during PCR and sequencing with Illumina MiSeq, PacBio RS II and PacBio Sequel I technologies. Fragment length variation was the main source of bias in observed community composition relative to the template, with longer fragments generally being under-represented for all sequencing platforms. This bias was three times higher for Illumina MiSeq than for PacBio RS II and Sequel I. All 10 fragments in the artificial community were recovered when sequenced with PacBio technologies, whereas the three longest fragments (> 447 bases) were lost when sequenced with Illumina MiSeq. Fragment length bias also increased linearly with increasing number of PCR cycles but could be mitigated by optimization of the PCR setup. No significant biases related to GC content were observed. Despite lower sequencing output, PacBio sequencing was better able to reflect the community composition of the template than Illumina MiSeq sequencing.", "doi": "10.1111/nph.16731", "pmid": "32531109", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [], "notes": [], "created": "2020-08-19T09:21:07.482Z", "modified": "2021-11-10T12:45:47.178Z"}, {"entity": "publication", "iuid": "2cb43ab5664d469db94c06796aaa296d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2cb43ab5664d469db94c06796aaa296d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2cb43ab5664d469db94c06796aaa296d"}}, "title": "Leaf shape in Populus tremula is a complex, omnigenic trait.", "authors": [{"family": "M\u00e4hler", "given": "Niklas", "initials": "N", "orcid": "0000-0003-2673-9113", "researcher": {"href": "https://publications.scilifelab.se/researcher/581734b34e9948438243f0c105e1094f.json"}}, {"family": "Schiffthaler", "given": "Bastian", "initials": "B", "orcid": "0000-0002-9771-467X", "researcher": {"href": "https://publications.scilifelab.se/researcher/12527c57f62e4a46b758e061ba3f80b1.json"}}, {"family": "Robinson", "given": "Kathryn M", "initials": "KM", "orcid": "0000-0002-5249-604X", "researcher": {"href": "https://publications.scilifelab.se/researcher/56d40626e73d49799c175a2ea14f5626.json"}}, {"family": "Terebieniec", "given": "Barbara K", "initials": "BK"}, {"family": "Vu\u010dak", "given": "Matej", "initials": "M", "orcid": "0000-0002-3181-2808", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e64ed41987741f392a5c352ec92480a.json"}}, {"family": "Mannapperuma", "given": "Chanaka", "initials": "C"}, {"family": "Bailey", "given": "Mark E S", "initials": "MES", "orcid": "0000-0002-9788-2278", "researcher": {"href": "https://publications.scilifelab.se/researcher/3919edd84f254870a5644770152360b6.json"}}, {"family": "Jansson", "given": "Stefan", "initials": "S", "orcid": "0000-0002-7906-6891", "researcher": {"href": "https://publications.scilifelab.se/researcher/fb9d3c17f4514903b3731d15c622a53d.json"}}, {"family": "Hvidsten", "given": "Torgeir R", "initials": "TR", "orcid": "0000-0001-6097-2539", "researcher": {"href": "https://publications.scilifelab.se/researcher/987fbb5763c74f6895bee64630528d8d.json"}}, {"family": "Street", "given": "Nathaniel R", "initials": "NR", "orcid": "0000-0001-6031-005X", "researcher": {"href": "https://publications.scilifelab.se/researcher/cb9ceb237a724046a1454179a32de1b0.json"}}], "type": "journal article", "published": "2020-11-00", "journal": {"title": "Ecol Evol", "issn": "2045-7758", "volume": "10", "issue": "21", "pages": "11922-11940", "issn-l": "2045-7758"}, "abstract": "Leaf shape is a defining feature of how we recognize and classify plant species. Although there is extensive variation in leaf shape within many species, few studies have disentangled the underlying genetic architecture. We characterized the genetic architecture of leaf shape variation in Eurasian aspen (Populus tremula L.) by performing genome-wide association study (GWAS) for physiognomy traits. To ascertain the roles of identified GWAS candidate genes within the leaf development transcriptional program, we generated RNA-Seq data that we used to perform gene co-expression network analyses from a developmental series, which is publicly available within the PlantGenIE resource. We additionally used existing gene expression measurements across the population to analyze GWAS candidate genes in the context of a population-wide co-expression network and to identify genes that were differentially expressed between groups of individuals with contrasting leaf shapes. These data were integrated with expression GWAS (eQTL) results to define a set of candidate genes associated with leaf shape variation. Our results identified no clear adaptive link to leaf shape variation and indicate that leaf shape traits are genetically complex, likely determined by numerous small-effect variations in gene expression. Genes associated with shape variation were peripheral within the population-wide co-expression network, were not highly connected within the leaf development co-expression network, and exhibited signatures of relaxed selection. As such, our results are consistent with the omnigenic model.", "doi": "10.1002/ece3.6691", "pmid": "33209260", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "ECE36691"}, {"db": "pmc", "key": "PMC7663049"}, {"db": "Dryad", "key": "10.5061/dryad.3n5tb2rdt"}], "notes": [], "created": "2020-12-07T16:34:40.237Z", "modified": "2024-01-16T13:48:41.464Z"}, {"entity": "publication", "iuid": "11f33634ab3146e69138a533798e7438", "links": {"self": {"href": "https://publications.scilifelab.se/publication/11f33634ab3146e69138a533798e7438.json"}, "display": {"href": "https://publications.scilifelab.se/publication/11f33634ab3146e69138a533798e7438"}}, "title": "Identification and rescue of a tRNA wobble inosine deficiency causing intellectual disability disorder.", "authors": [{"family": "Ramos", "given": "Jillian", "initials": "J", "orcid": "0000-0001-8139-5793", "researcher": {"href": "https://publications.scilifelab.se/researcher/d56276e8c1ca41c7afe82887f174caf4.json"}}, {"family": "Proven", "given": "Melissa", "initials": "M"}, {"family": "Halvardson", "given": "Jonatan", "initials": "J"}, {"family": "Hagelskamp", "given": "Felix", "initials": "F"}, {"family": "Kuchinskaya", "given": "Ekaterina", "initials": "E"}, {"family": "Phelan", "given": "Benjamin", "initials": "B"}, {"family": "Bell", "given": "Ryan", "initials": "R"}, {"family": "Kellner", "given": "Stefanie M", "initials": "SM"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Thuresson", "given": "Ann-Charlotte", "initials": "AC"}, {"family": "Fu", "given": "Dragony", "initials": "D", "orcid": "0000-0002-8725-8658", "researcher": {"href": "https://publications.scilifelab.se/researcher/77103dd473a54326a9af7151af9d2ef7.json"}}], "type": "journal article", "published": "2020-11-00", "journal": {"title": "RNA", "issn": "1469-9001", "issn-l": "1355-8382", "volume": "26", "issue": "11", "pages": "1654-1666"}, "abstract": "The deamination of adenosine to inosine at the wobble position of tRNA is an essential post-transcriptional RNA modification required for wobble decoding in bacteria and eukaryotes. In humans, the wobble inosine modification is catalyzed by the heterodimeric ADAT2/3 complex. Here, we describe novel pathogenic ADAT3 variants impairing adenosine deaminase activity through a distinct mechanism that can be corrected through expression of the heterodimeric ADAT2 subunit. The variants were identified in a family in which all three siblings exhibit intellectual disability linked to biallelic variants in the ADAT3 locus. The biallelic ADAT3 variants result in a missense variant converting alanine to valine at a conserved residue or the introduction of a premature stop codon in the deaminase domain. Fibroblast cells derived from two ID-affected individuals exhibit a reduction in tRNA wobble inosine levels and severely diminished adenosine tRNA deaminase activity. Notably, the ADAT3 variants exhibit impaired interaction with the ADAT2 subunit and alterations in ADAT2-dependent nuclear localization. Based upon these findings, we find that tRNA adenosine deaminase activity and wobble inosine modification can be rescued in patient cells by overexpression of the ADAT2 catalytic subunit. These results uncover a key role for the inactive ADAT3 deaminase domain in proper assembly with ADAT2 and demonstrate that ADAT2/3 nuclear import is required for maintaining proper levels of the wobble inosine modification in tRNA.", "doi": "10.1261/rna.076380.120", "pmid": "32763916", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Service", "National Genomics Infrastructure": "Service", "Clinical Genomics Uppsala": "Collaborative", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "rna.076380.120"}, {"db": "pmc", "key": "PMC7566568"}], "notes": [], "created": "2020-09-15T07:06:13.955Z", "modified": "2024-01-16T13:48:41.471Z"}, {"entity": "publication", "iuid": "f3ea7ecc69e24f00b6d9979e061dd885", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f3ea7ecc69e24f00b6d9979e061dd885.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f3ea7ecc69e24f00b6d9979e061dd885"}}, "title": "Human G-MDSCs are neutrophils at distinct maturation stages promoting tumor growth in breast cancer", "authors": [{"family": "Mehmeti-Ajradini", "given": "Meliha", "initials": "M"}, {"family": "Bergenfelz", "given": "Caroline", "initials": "C"}, {"family": "Larsson", "given": "Anna Maria", "initials": "AM"}, {"family": "Carlsson", "given": "Robert", "initials": "R"}, {"family": "Riesbeck", "given": "Kristian", "initials": "K", "orcid": "0000-0001-6274-6965", "researcher": {"href": "https://publications.scilifelab.se/researcher/d757ccad30b043748c8fe48a7308210c.json"}}, {"family": "Ahl", "given": "Jonas", "initials": "J"}, {"family": "Janols", "given": "Helena", "initials": "H"}, {"family": "Wullt", "given": "Marlene", "initials": "M"}, {"family": "Bredberg", "given": "Anders", "initials": "A"}, {"family": "K\u00e4llberg", "given": "Eva", "initials": "E"}, {"family": "Bj\u00f6rk Gunnarsdottir", "given": "Frida", "initials": "F"}, {"family": "Rydberg Millrud", "given": "Camilla", "initials": "C"}, {"family": "Ryd\u00e9n", "given": "Lisa", "initials": "L", "orcid": "0000-0001-7515-3130", "researcher": {"href": "https://publications.scilifelab.se/researcher/424bace557344431a47ffe5cdccbeb56.json"}}, {"family": "Paul", "given": "Gesine", "initials": "G"}, {"family": "Loman", "given": "Niklas", "initials": "N"}, {"family": "Adolfsson", "given": "J\u00f6rgen", "initials": "J"}, {"family": "Carneiro", "given": "Ana", "initials": "A", "orcid": "0000-0002-1818-7008", "researcher": {"href": "https://publications.scilifelab.se/researcher/12ef95bff08743398bf3a374195e043e.json"}}, {"family": "Jirstr\u00f6m", "given": "Karin", "initials": "K"}, {"family": "Killander", "given": "Fredrika", "initials": "F"}, {"family": "Bexell", "given": "Daniel", "initials": "D"}, {"family": "Leandersson", "given": "Karin", "initials": "K", "orcid": "0000-0001-8254-3137", "researcher": {"href": "https://publications.scilifelab.se/researcher/4736923f382845c2990efb251340bfb4.json"}}], "type": "journal-article", "published": "2020-11-00", "journal": {"title": "Life Sci. Alliance", "issn": "2575-1077", "issn-l": "2575-1077", "volume": "3", "issue": "11", "pages": "e202000893"}, "abstract": "Myeloid-derived suppressor cells (MDSCs) are known to contribute to immune evasion in cancer. However, the function of the human granulocytic (G)-MDSC subset during tumor progression is largely unknown, and there are no established markers for their identification in human tumor specimens. Using gene expression profiling, mass cytometry, and tumor microarrays, we here demonstrate that human G-MDSCs occur as neutrophils at distinct maturation stages, with a disease-specific profile. G-MDSCs derived from patients with metastatic breast cancer and malignant melanoma display a unique immature neutrophil profile, that is more similar to healthy donor neutrophils than to G-MDSCs from sepsis patients. Finally, we show that primary G-MDSCs from metastatic breast cancer patients co-transplanted with breast cancer cells, promote tumor growth, and affect vessel formation, leading to myeloid immune cell exclusion. Our findings reveal a role for human G-MDSC in tumor progression and have clinical implications also for targeted immunotherapy.", "doi": "10.26508/lsa.202000893", "pmid": "32958605", "labels": {"Cellular Immunomonitoring": "Service", "Bioinformatics Support, Infrastructure and Training": "Service", "Bioinformatics Support and Infrastructure": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7536824"}, {"db": "pii", "key": "3/11/e202000893"}], "notes": [], "created": "2020-09-24T15:35:44.836Z", "modified": "2024-11-15T09:54:18.581Z"}, {"entity": "publication", "iuid": "da7a890736f04a11bf851615d6ddf028", "links": {"self": {"href": "https://publications.scilifelab.se/publication/da7a890736f04a11bf851615d6ddf028.json"}, "display": {"href": "https://publications.scilifelab.se/publication/da7a890736f04a11bf851615d6ddf028"}}, "title": "Epilepsy syndromes, etiologies, and the use of next-generation sequencing in epilepsy presenting in the first 2 years of life: A population-based study.", "authors": [{"family": "St\u00f6dberg", "given": "Tommy", "initials": "T", "orcid": "0000-0003-1242-5260", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae8c80e14d814232a164040f24fc6acd.json"}}, {"family": "Tomson", "given": "Torbj\u00f6rn", "initials": "T", "orcid": "0000-0003-0554-5352", "researcher": {"href": "https://publications.scilifelab.se/researcher/f001d5b4949547e2bb390af5463b50f5.json"}}, {"family": "Barbaro", "given": "Michela", "initials": "M"}, {"family": "Stranneheim", "given": "Henrik", "initials": "H"}, {"family": "Anderlid", "given": "Britt-Marie", "initials": "BM"}, {"family": "Carlsson", "given": "Sofia", "initials": "S"}, {"family": "\u00c5mark", "given": "Per", "initials": "P"}, {"family": "Wedell", "given": "Anna", "initials": "A", "orcid": "0000-0002-2612-6301", "researcher": {"href": "https://publications.scilifelab.se/researcher/15f660ec95994b6a83d540e48c9b7610.json"}}], "type": "journal article", "published": "2020-11-00", "journal": {"title": "Epilepsia", "issn": "1528-1167", "volume": "61", "issue": "11", "pages": "2486-2499", "issn-l": "0013-9580"}, "abstract": "Population-based data on epilepsy syndromes and etiologies in early onset epilepsy are scarce. The use of next-generation sequencing (NGS) has hitherto not been reported in this context. The aim of this study is to describe children with epilepsy onset before 2 years of age, and to explore to what degree whole exome and whole genome sequencing (WES/WGS) can help reveal a molecular genetic diagnosis.\n\nChildren presenting with a first unprovoked epileptic seizure before age 2 years and registered in the Stockholm Incidence Registry of Epilepsy (SIRE) between September 1, 2001 and December 31, 2006, were retrieved and their medical records up to age 7 years reviewed. Children who met the epilepsy criteria were included in the study cohort. WES/WGS was offered in cases of suspected genetic etiology regardless of whether a structural or metabolic diagnosis had been established.\n\nOne hundred sixteen children were included, of which 88 had seizure onset during the first year of life and 28 during the second, corresponding to incidences of 139 and 42/100 000 person-years, respectively. An epilepsy syndrome could be diagnosed in 54% of cases, corresponding to a birth prevalence of 1/1100. Structural etiology was revealed in 34% of cases, a genetic cause in 20%, and altogether etiology was known in 65% of children. The highest diagnostic yield was seen in magnetic resonance imaging (MRI) with 65% revealing an etiology. WES/WGS was performed in 26/116 cases (22%), with a diagnostic yield of 58%.\n\nEpilepsy syndromes can be diagnosed and etiologies revealed in a majority of early onset cases. NGS can identify a molecular diagnosis in a substantial number of children, and should be included in the work-up, especially in cases of epileptic encephalopathy, cerebral malformation, or metabolic disease without molecular diagnosis. A genetic diagnosis is essential to genetic counselling, prenatal diagnostics, and precision therapy.", "doi": "10.1111/epi.16701", "pmid": "32964447", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7756847"}], "notes": [], "created": "2020-11-22T16:13:01.434Z", "modified": "2021-11-10T12:47:06.774Z"}, {"entity": "publication", "iuid": "6cf27411c92e4ca09122a8fdb288c1fa", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6cf27411c92e4ca09122a8fdb288c1fa.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6cf27411c92e4ca09122a8fdb288c1fa"}}, "title": "Divergent above- and below-ground responses of fungal functional groups to forest thinning", "authors": [{"family": "Collado", "given": "Eduardo", "initials": "E"}, {"family": "Casta\u00f1o", "given": "Carles", "initials": "C"}, {"family": "Bonet", "given": "Jos\u00e9 Antonio", "initials": "JA"}, {"family": "Hagenbo", "given": "Andreas", "initials": "A"}, {"family": "Mart\u00ednez de Arag\u00f3n", "given": "Juan", "initials": "J"}, {"family": "de-Miguel", "given": "Sergio", "initials": "S"}], "type": "journal-article", "published": "2020-11-00", "journal": {"title": "Soil Biology and Biochemistry", "issn": "0038-0717", "volume": "150", "issue": null, "pages": "108010", "issn-l": null}, "abstract": null, "doi": "10.1016/j.soilbio.2020.108010", "pmid": null, "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service"}, "xrefs": [], "notes": [], "created": "2020-09-25T05:15:27.002Z", "modified": "2021-11-10T12:34:24.915Z"}, {"entity": "publication", "iuid": "0cd1833de8764e41812f14260f5961b5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0cd1833de8764e41812f14260f5961b5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0cd1833de8764e41812f14260f5961b5"}}, "title": "Dense sampling of bird diversity increases power of comparative genomics.", "authors": [{"family": "Feng", "given": "Shaohong", "initials": "S", "orcid": "0000-0002-2462-7348", "researcher": {"href": "https://publications.scilifelab.se/researcher/92ad360b09004877aee9cfde491c76a3.json"}}, {"family": "Stiller", "given": "Josefin", "initials": "J", "orcid": "0000-0001-6009-9581", "researcher": {"href": "https://publications.scilifelab.se/researcher/9e54e7b719bb422aa18ccd99d6c2edf6.json"}}, {"family": "Deng", "given": "Yuan", "initials": "Y"}, {"family": "Armstrong", "given": "Joel", "initials": "J", "orcid": "0000-0003-2077-4671", "researcher": {"href": "https://publications.scilifelab.se/researcher/63cfeea6ae9942b8a48e6e13ecf4bf0d.json"}}, {"family": "Fang", "given": "Qi", "initials": "Q", "orcid": "0000-0002-9181-8689", "researcher": {"href": "https://publications.scilifelab.se/researcher/b9ff76a9a8bb42c8973d968c7e39a216.json"}}, {"family": "Reeve", "given": "Andrew Hart", "initials": "AH", "orcid": "0000-0001-5233-6030", "researcher": {"href": "https://publications.scilifelab.se/researcher/c9c0cc8c4ff44848960ec2d43dce41d7.json"}}, {"family": "Xie", "given": "Duo", "initials": "D", "orcid": "0000-0001-7010-3601", "researcher": {"href": "https://publications.scilifelab.se/researcher/9258a952a3c54596add7d930e1432ebe.json"}}, {"family": "Chen", "given": "Guangji", "initials": "G", "orcid": "0000-0002-9441-1155", "researcher": {"href": "https://publications.scilifelab.se/researcher/19514f67b1504dc6b4b7d393e97f8cc0.json"}}, {"family": "Guo", "given": "Chunxue", "initials": "C"}, {"family": "Faircloth", "given": "Brant C", "initials": "BC", "orcid": "0000-0002-1943-0217", "researcher": {"href": "https://publications.scilifelab.se/researcher/6df01b37d97a44ffb6f4d069085d7b64.json"}}, {"family": "Petersen", "given": "Bent", "initials": "B", "orcid": "0000-0002-2472-8317", "researcher": {"href": "https://publications.scilifelab.se/researcher/62045d9b6dc443be936d3346daa4e1b1.json"}}, {"family": "Wang", "given": "Zongji", "initials": "Z", "orcid": "0000-0002-5107-6246", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a18bde0ee684560ae3217db4b30a920.json"}}, {"family": "Zhou", "given": "Qi", "initials": "Q", "orcid": "0000-0002-7419-2047", "researcher": {"href": "https://publications.scilifelab.se/researcher/a69266aa587d4126a23aa91c5bedfff8.json"}}, {"family": "Diekhans", "given": "Mark", "initials": "M", "orcid": "0000-0002-0430-0989", "researcher": {"href": "https://publications.scilifelab.se/researcher/da3441938f7b437b81cc92068bea158c.json"}}, {"family": "Chen", "given": "Wanjun", "initials": "W", "orcid": "0000-0002-4418-7650", "researcher": {"href": "https://publications.scilifelab.se/researcher/992e7029a2704d039ce578df2806f57f.json"}}, {"family": "Andreu-S\u00e1nchez", "given": "Sergio", "initials": "S"}, {"family": "Margaryan", "given": "Ashot", "initials": "A", "orcid": "0000-0002-2576-2429", "researcher": {"href": "https://publications.scilifelab.se/researcher/487f29e4a666414a8437f964e2052be7.json"}}, {"family": "Howard", "given": "Jason Travis", "initials": "JT"}, {"family": "Parent", "given": "Carole", "initials": "C"}, {"family": "Pacheco", "given": "George", "initials": "G", "orcid": "0000-0002-9367-6813", "researcher": {"href": "https://publications.scilifelab.se/researcher/449f532c61df4157b9bd1dc15deab965.json"}}, {"family": "Sinding", "given": "Mikkel-Holger S", "initials": "MS", "orcid": "0000-0003-1371-219X", "researcher": {"href": "https://publications.scilifelab.se/researcher/c37b07e1cb9643279b8801c45dde9dbe.json"}}, {"family": "Puetz", "given": "Lara", "initials": "L", "orcid": "0000-0002-0323-799X", "researcher": {"href": "https://publications.scilifelab.se/researcher/986da811e11341379e73f5382b0f69ad.json"}}, {"family": "Cavill", "given": "Emily", "initials": "E", "orcid": "0000-0003-2198-8102", "researcher": {"href": "https://publications.scilifelab.se/researcher/eacd61b411f046d88c1e8942eb46cfff.json"}}, {"family": "Ribeiro", "given": "\u00c2ngela M", "initials": "\u00c2M"}, {"family": "Eckhart", "given": "Leopold", "initials": "L", "orcid": "0000-0002-5645-2036", "researcher": {"href": "https://publications.scilifelab.se/researcher/76a24adae52741698457e9a733f36f6c.json"}}, {"family": "Fjelds\u00e5", "given": "Jon", "initials": "J", "orcid": "0000-0003-0790-3600", "researcher": {"href": "https://publications.scilifelab.se/researcher/f280ada51dfb41b2a3d035676a27ffb6.json"}}, {"family": "Hosner", "given": "Peter A", "initials": "PA", "orcid": "0000-0001-7499-6224", "researcher": {"href": "https://publications.scilifelab.se/researcher/87a4c8cd6229436d9a39761aa77eeec2.json"}}, {"family": "Brumfield", "given": "Robb T", "initials": "RT", "orcid": "0000-0003-2307-0688", "researcher": {"href": "https://publications.scilifelab.se/researcher/71a3a36f83154d3dbe14e1a5290f425f.json"}}, {"family": "Christidis", "given": "Les", "initials": "L", "orcid": "0000-0002-3345-6034", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd916cfab85848b683744b92f994bd74.json"}}, {"family": "Bertelsen", "given": "Mads F", "initials": "MF"}, {"family": "Sicheritz-Ponten", "given": "Thomas", "initials": "T", "orcid": "0000-0001-6615-1141", "researcher": {"href": "https://publications.scilifelab.se/researcher/0da5029f417945a790fbb57b5120dceb.json"}}, {"family": "Tietze", "given": "Dieter Thomas", "initials": "DT", "orcid": "0000-0001-6868-227X", "researcher": {"href": "https://publications.scilifelab.se/researcher/820c40b8230d46fca4c8f6d6af483f71.json"}}, {"family": "Robertson", "given": "Bruce C", "initials": "BC", "orcid": "0000-0002-5348-2731", "researcher": {"href": "https://publications.scilifelab.se/researcher/765ee347a5f04b29b28a17f14f707231.json"}}, {"family": "Song", "given": "Gang", "initials": "G", "orcid": "0000-0002-0190-8315", "researcher": {"href": "https://publications.scilifelab.se/researcher/f133bb6165494dfaba8173b0e8191765.json"}}, {"family": "Borgia", "given": "Gerald", "initials": "G"}, {"family": "Claramunt", "given": "Santiago", "initials": "S", "orcid": "0000-0002-8926-5974", "researcher": {"href": "https://publications.scilifelab.se/researcher/24bba44e15a14f3fa2798de2f0f86f55.json"}}, {"family": "Lovette", "given": "Irby J", "initials": "IJ", "orcid": "0000-0003-0268-4875", "researcher": {"href": "https://publications.scilifelab.se/researcher/7f3e74e4c49e4a7f8ce6109e255cbb1c.json"}}, {"family": "Cowen", "given": "Saul J", "initials": "SJ", "orcid": "0000-0002-1045-5637", "researcher": {"href": "https://publications.scilifelab.se/researcher/e9565f0452e343c89113e611942e3285.json"}}, {"family": "Njoroge", "given": "Peter", "initials": "P", "orcid": "0000-0003-1165-3579", "researcher": {"href": "https://publications.scilifelab.se/researcher/99cda46acb47431eb59b7a4a25b103f0.json"}}, {"family": "Dumbacher", "given": "John Philip", "initials": "JP", "orcid": "0000-0001-8942-1554", "researcher": {"href": "https://publications.scilifelab.se/researcher/6221be035944462989353d66f126a5c5.json"}}, {"family": "Ryder", "given": "Oliver A", "initials": "OA", "orcid": "0000-0003-2427-763X", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a55f8ea442f4168a8426ae4a2c43a46.json"}}, {"family": "Fuchs", "given": "J\u00e9r\u00f4me", "initials": "J", "orcid": "0000-0003-1972-0078", "researcher": {"href": "https://publications.scilifelab.se/researcher/2976574cfb9b423cb487dcf840619c94.json"}}, {"family": "Bunce", "given": "Michael", "initials": "M", "orcid": "0000-0002-0302-4206", "researcher": {"href": "https://publications.scilifelab.se/researcher/6a6cb7d93e7c4785a0334adaf12aca6b.json"}}, {"family": "Burt", "given": "David W", "initials": "DW", "orcid": "0000-0002-9991-1028", "researcher": {"href": "https://publications.scilifelab.se/researcher/eb2c7a18d5b64136b08fa00cf65624e5.json"}}, {"family": "Cracraft", "given": "Joel", "initials": "J", "orcid": "0000-0001-7587-8342", "researcher": {"href": "https://publications.scilifelab.se/researcher/99c4c500419d491c96654e37210dee27.json"}}, {"family": "Meng", "given": "Guanliang", "initials": "G", "orcid": "0000-0002-6488-1527", "researcher": {"href": "https://publications.scilifelab.se/researcher/7191d467d9b3497f80212ff402c8f9cd.json"}}, {"family": "Hackett", "given": "Shannon J", "initials": "SJ", "orcid": "0000-0002-1404-0332", "researcher": {"href": "https://publications.scilifelab.se/researcher/ac60e949323442e39e2e53b03610f99f.json"}}, {"family": "Ryan", "given": "Peter G", "initials": "PG"}, {"family": "J\u00f8nsson", "given": "Knud Andreas", "initials": "KA", "orcid": "0000-0002-1875-9504", "researcher": {"href": "https://publications.scilifelab.se/researcher/ca007307f40c49d2baa3420c3fc61d02.json"}}, {"family": "Jamieson", "given": "Ian G", "initials": "IG"}, {"family": "da Fonseca", "given": "Rute R", "initials": "RR", "orcid": 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"initials": "B"}, {"family": "Taylor", "given": "Scott A", "initials": "SA", "orcid": "0000-0001-9580-9125", "researcher": {"href": "https://publications.scilifelab.se/researcher/36c6baa1b23242e0bfd586d7e42c0cb9.json"}}, {"family": "Del-Rio", "given": "Glaucia", "initials": "G"}, {"family": "Aleixo", "given": "Alexandre", "initials": "A", "orcid": "0000-0002-7816-9725", "researcher": {"href": "https://publications.scilifelab.se/researcher/b397ed6da07246caa50a438c233820ab.json"}}, {"family": "Vasconcelos", "given": "Ana Tereza Ribeiro", "initials": "ATR", "orcid": "0000-0002-4632-2086", "researcher": {"href": "https://publications.scilifelab.se/researcher/69b1022e72a84534850b8d650ba2c1be.json"}}, {"family": "Mello", "given": "Claudio V", "initials": "CV", "orcid": "0000-0002-9826-8421", "researcher": {"href": "https://publications.scilifelab.se/researcher/e9715cacaf7d45bda2337a32ea0ec526.json"}}, {"family": "Weir", "given": "Jason T", "initials": "JT", "orcid": "0000-0001-8372-9937", "researcher": {"href": "https://publications.scilifelab.se/researcher/8c77b745d8b044d4aed9478d056be226.json"}}, {"family": "Haussler", "given": "David", "initials": "D", "orcid": "0000-0003-1533-4575", "researcher": {"href": "https://publications.scilifelab.se/researcher/de140026a4f24291be768e713e4881bb.json"}}, {"family": "Li", "given": "Qiye", "initials": "Q", "orcid": "0000-0002-5993-0312", "researcher": {"href": "https://publications.scilifelab.se/researcher/d807a3a13669425c9b00e4a2b7db672a.json"}}, {"family": "Yang", "given": "Huanming", "initials": "H"}, {"family": "Wang", "given": "Jian", "initials": "J"}, {"family": "Lei", "given": "Fumin", "initials": "F"}, {"family": "Rahbek", "given": "Carsten", "initials": "C"}, {"family": "Gilbert", "given": "M Thomas P", "initials": "MTP", "orcid": "0000-0002-5805-7195", "researcher": {"href": "https://publications.scilifelab.se/researcher/873e2383b99a43d7848bf387264cf0e8.json"}}, {"family": "Graves", "given": "Gary R", "initials": "GR", "orcid": "0000-0003-1406-5246", "researcher": {"href": "https://publications.scilifelab.se/researcher/bc3b9edee185456d971f5b596c3086fe.json"}}, {"family": "Jarvis", "given": "Erich D", "initials": "ED", "orcid": "0000-0001-8931-5049", "researcher": {"href": "https://publications.scilifelab.se/researcher/d565d5e1788e484d9d2da61af12f2120.json"}}, {"family": "Paten", "given": "Benedict", "initials": "B", "orcid": "0000-0001-8863-3539", "researcher": {"href": "https://publications.scilifelab.se/researcher/956ebe9c0b6e43d7ac2a568519f43431.json"}}, {"family": "Zhang", "given": "Guojie", "initials": "G", "orcid": "0000-0001-6860-1521", "researcher": {"href": "https://publications.scilifelab.se/researcher/62f3c7981a1c43909817e72519232ff8.json"}}], "type": "journal article", "published": "2020-11-00", "journal": {"title": "Nature", "issn": "1476-4687", "volume": "587", "issue": "7833", "pages": "252-257", "issn-l": "0028-0836"}, "abstract": "Whole-genome sequencing projects are increasingly populating the tree of life and characterizing biodiversity1-4. Sparse taxon sampling has previously been proposed to confound phylogenetic inference5, and captures only a fraction of the genomic diversity. Here we report a substantial step towards the dense representation of avian phylogenetic and molecular diversity, by analysing 363 genomes from 92.4% of bird families-including 267 newly sequenced genomes produced for phase II of the Bird 10,000 Genomes (B10K) Project. We use this comparative genome dataset in combination with a pipeline that leverages a reference-free whole-genome alignment to identify orthologous regions in greater numbers than has previously been possible and to recognize genomic novelties in particular bird lineages. The densely sampled alignment provides a single-base-pair map of selection, has more than doubled the fraction of bases that are confidently predicted to be under conservation and reveals extensive patterns of weak selection in predominantly non-coding DNA. Our results demonstrate that increasing the diversity of genomes used in comparative studies can reveal more shared and lineage-specific variation, and improve the investigation of genomic characteristics. We anticipate that this genomic resource will offer new perspectives on evolutionary processes in cross-species comparative analyses and assist in efforts to conserve species.", "doi": "10.1038/s41586-020-2873-9", "pmid": "33177665", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41586-020-2873-9"}, {"db": "pmc", "key": "PMC7759463"}], "notes": [], "created": "2020-12-07T16:36:44.079Z", "modified": "2021-11-10T12:45:51.851Z"}, {"entity": "publication", "iuid": "9003c13437864efc9e4e530ff7595ac6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9003c13437864efc9e4e530ff7595ac6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9003c13437864efc9e4e530ff7595ac6"}}, "title": "Cytogenetically visible inversions are formed by multiple molecular mechanisms.", "authors": [{"family": "Pettersson", "given": "Maria", "initials": "M", "orcid": "0000-0003-3120-1625", "researcher": {"href": "https://publications.scilifelab.se/researcher/bfdfac2208ce4d1a877fa4957e2f4ea4.json"}}, {"family": "Grochowski", "given": "Christopher M", "initials": "CM", "orcid": "0000-0002-3884-7720", "researcher": {"href": "https://publications.scilifelab.se/researcher/c94bd6d4a43e41f2990ae8b9426c0312.json"}}, {"family": "Wincent", "given": "Josephine", "initials": "J"}, {"family": "Eisfeldt", "given": "Jesper", "initials": "J", "orcid": "0000-0003-3716-4917", "researcher": {"href": "https://publications.scilifelab.se/researcher/32a701ee07674785b48b047665e18ee6.json"}}, {"family": "Breman", "given": "Amy M", "initials": "AM"}, {"family": "Cheung", "given": "Sau W", "initials": "SW"}, {"family": "Krepischi", "given": "Ana C V", "initials": "ACV"}, {"family": "Rosenberg", "given": "Carla", "initials": "C"}, {"family": "Lupski", "given": "James R", "initials": "JR", "orcid": "0000-0001-9907-9246", "researcher": {"href": "https://publications.scilifelab.se/researcher/88dd1dee9767489aaf25865670feb7b7.json"}}, {"family": "Ottosson", "given": "Jesper", "initials": "J"}, {"family": "Lovmar", "given": "Lovisa", "initials": "L"}, {"family": "Gacic", "given": "Jelena", "initials": "J"}, {"family": "Lundberg", "given": "Elisabeth S", "initials": "ES"}, {"family": "Nilsson", "given": "Daniel", "initials": "D"}, {"family": "Carvalho", "given": "Claudia M B", "initials": "CMB", "orcid": "0000-0002-2090-298X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3a1a6b6936aa442384c5aef0eff0715a.json"}}, {"family": "Lindstrand", "given": "Anna", "initials": "A", "orcid": "0000-0003-0806-5602", "researcher": {"href": "https://publications.scilifelab.se/researcher/07f3e6152da043d38c7a81974fcf8c23.json"}}], "type": "journal article", "published": "2020-11-00", "journal": {"title": "Hum. Mutat.", "issn": "1098-1004", "volume": "41", "issue": "11", "pages": "1979-1998", "issn-l": "1059-7794"}, "abstract": "Cytogenetically detected inversions are generally assumed to be copy number and phenotypically neutral events. While nonallelic homologous recombination is thought to play a major role, recent data suggest the involvement of other molecular mechanisms in inversion formation. Using a combination of short-read whole-genome sequencing (WGS), 10X Genomics Chromium WGS, droplet digital polymerase chain reaction and array comparative genomic hybridization we investigated the genomic structure of 18 large unique cytogenetically detected chromosomal inversions and achieved nucleotide resolution of at least one chromosomal inversion junction for 13/18 (72%). Surprisingly, we observed that seemingly copy number neutral inversions can be accompanied by a copy-number gain of up to 350 kb and local genomic complexities (3/18, 17%). In the resolved inversions, the mutational signatures are consistent with nonhomologous end-joining (8/13, 62%) or microhomology-mediated break-induced replication (5/13, 38%). Our study indicates that short-read 30x coverage WGS can detect a substantial fraction of chromosomal inversions. Moreover, replication-based mechanisms are responsible for approximately 38% of those events leading to a significant proportion of inversions that are actually accompanied by additional copy-number variation potentially contributing to the overall phenotypic presentation of those patients.", "doi": "10.1002/humu.24106", "pmid": "32906200", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7702065"}], "notes": [], "created": "2020-12-07T16:28:51.266Z", "modified": "2024-01-16T13:48:41.478Z"}, {"entity": "publication", "iuid": "3648126ca4f64fc7a30a03f8065b00fd", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3648126ca4f64fc7a30a03f8065b00fd.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3648126ca4f64fc7a30a03f8065b00fd"}}, "title": "A family-based genome-wide association study of recurrent aphthous stomatitis.", "authors": [{"family": "Bankvall", "given": "Maria", "initials": "M", "orcid": "0000-0003-3949-6739", "researcher": {"href": "https://publications.scilifelab.se/researcher/aa1610a7b02e4460a6da70cd0ee8ae80.json"}}, {"family": "\u00d6stman", "given": "Sofia", "initials": "S"}, {"family": "Jontell", "given": "Mats", "initials": "M"}, {"family": "Torinsson Naluai", "given": "\u00c5sa", "initials": "\u00c5"}], "type": "journal article", "published": "2020-11-00", "journal": {"title": "Oral Dis", "issn": "1601-0825", "volume": "26", "issue": "8", "pages": "1696-1705", "issn-l": "1354-523X"}, "abstract": "The aetiology of recurrent aphthous stomatitis (RAS) remains unknown. Individuals may share features of genetic susceptibility, and there may also be a hereditary component. The aim was to identify patterns of association and segregation for genetic variants and to identify the genes and signalling pathways that determine the risk of developing RAS, through a family-based genome-wide association study (GWAS).\n\nDNA was extracted from buccal swabs of 91 individuals in 16 families and analysed in an Illumina core exome single nucleotide polymorphism (SNP) array. A family-based association test (dFAM) was used to derive SNP association values across all chromosomes.\n\nNone of the final 288,452 SNPs reached the genome-wide significant threshold of 5 \u00d7 10-8 . The most significant pathways were the Ras and PI3K-Akt signalling pathways, pathways in cancer, circadian entrainment and the Rap 1 signalling pathway.\n\nThis confirms that RAS is not monogenic but results as a consequence of interactions between multiple host genes and possibly also environmental factors. The present approach provides novel insights into the mechanisms underlying RAS and raises the possibility of identifying individuals at risk of acquiring this condition.", "doi": "10.1111/odi.13490", "pmid": "32558109", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [], "notes": [], "created": "2020-06-23T11:11:11.532Z", "modified": "2021-11-10T12:45:55.331Z"}, {"entity": "publication", "iuid": "a4c3fac414964931b8a6301041dbf23d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a4c3fac414964931b8a6301041dbf23d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a4c3fac414964931b8a6301041dbf23d"}}, "title": "A comparative genomics multitool for scientific discovery and conservation.", "authors": [{"family": "Zoonomia Consortium", "given": "", "initials": ""}], "type": "journal article", "published": "2020-11-00", "journal": {"title": "Nature", "issn": "1476-4687", "volume": "587", "issue": "7833", "pages": "240-245", "issn-l": "0028-0836"}, "abstract": "The Zoonomia Project is investigating the genomics of shared and specialized traits in eutherian mammals. Here we provide genome assemblies for 131 species, of which all but 9 are previously uncharacterized, and describe a whole-genome alignment of 240 species of considerable phylogenetic diversity, comprising representatives from more than 80% of mammalian families. We find that regions of reduced genetic diversity are more abundant in species at a high risk of extinction, discern signals of evolutionary selection at high resolution and provide insights from individual reference genomes. By prioritizing phylogenetic diversity and making data available quickly and without restriction, the Zoonomia Project aims to support biological discovery, medical research and the conservation of biodiversity.", "doi": "10.1038/s41586-020-2876-6", "pmid": "33177664", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41586-020-2876-6"}, {"db": "pmc", "key": "PMC7759459"}], "notes": [], "created": "2021-06-01T20:49:28.688Z", "modified": "2021-11-10T12:45:56.515Z"}, {"entity": "publication", "iuid": "ffa17d5833774c64ae24d57daf592ed5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ffa17d5833774c64ae24d57daf592ed5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ffa17d5833774c64ae24d57daf592ed5"}}, "title": "Origins and genetic legacy of prehistoric dogs.", "authors": [{"family": "Bergstr\u00f6m", "given": "Anders", "initials": "A", "orcid": "0000-0002-4096-9268", "researcher": {"href": "https://publications.scilifelab.se/researcher/77429e0da9574e9ab3d1a14ae5dbb803.json"}}, {"family": "Frantz", "given": "Laurent", "initials": "L", "orcid": "0000-0001-8030-3885", "researcher": {"href": "https://publications.scilifelab.se/researcher/76b1179f8ee34ebbbdd466fb977f3ce7.json"}}, {"family": "Schmidt", "given": "Ryan", "initials": "R"}, {"family": "Ersmark", "given": "Erik", "initials": "E", "orcid": "0000-0003-4186-7498", "researcher": {"href": "https://publications.scilifelab.se/researcher/7061c3d9591b40488954083d06ed2e17.json"}}, {"family": "Lebrasseur", "given": "Ophelie", "initials": "O", "orcid": "0000-0003-0687-8538", "researcher": {"href": "https://publications.scilifelab.se/researcher/10f100bd635446739f54bcabbf1840bc.json"}}, {"family": "Girdland-Flink", "given": "Linus", "initials": "L"}, {"family": "Lin", "given": "Audrey T", "initials": "AT", "orcid": "0000-0003-2505-1480", "researcher": {"href": "https://publications.scilifelab.se/researcher/4f1f6e691ce04fd396757c4918535cc2.json"}}, {"family": "Stor\u00e5", "given": "Jan", "initials": "J", "orcid": "0000-0001-6319-7857", "researcher": {"href": "https://publications.scilifelab.se/researcher/57e9174cbd2a4c39be948b88b9ab2d3a.json"}}, {"family": "Sj\u00f6gren", "given": "Karl-G\u00f6ran", "initials": "KG", "orcid": "0000-0003-1791-3175", "researcher": {"href": "https://publications.scilifelab.se/researcher/1fe55ca79f7a438dbbda3e97e3780223.json"}}, {"family": "Anthony", "given": "David", "initials": "D", "orcid": "0000-0001-9122-0313", "researcher": {"href": "https://publications.scilifelab.se/researcher/dfe0401df8e44a82a3c69a7a0478007d.json"}}, {"family": "Antipina", "given": "Ekaterina", "initials": "E", "orcid": "0000-0002-3003-942X", "researcher": {"href": "https://publications.scilifelab.se/researcher/52c0ad9634824dabbef732e81a68ec60.json"}}, {"family": "Amiri", "given": "Sarieh", "initials": "S", "orcid": "0000-0002-6835-373X", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae40113ed34f4ed1a173637c864e1c38.json"}}, {"family": "Bar-Oz", "given": "Guy", "initials": "G"}, {"family": "Bazaliiskii", "given": "Vladimir I", "initials": "VI"}, {"family": "Bulatovi\u0107", "given": "Jelena", "initials": "J", "orcid": "0000-0002-0672-067X", "researcher": {"href": "https://publications.scilifelab.se/researcher/977f7acdf2e94256bc664d52f8b99922.json"}}, {"family": "Brown", "given": "Dorcas", "initials": "D"}, {"family": "Carmagnini", "given": "Alberto", "initials": "A"}, {"family": "Davy", "given": "Tom", "initials": "T", "orcid": "0000-0002-9466-5497", "researcher": {"href": "https://publications.scilifelab.se/researcher/2c9e9bebf8ad41d2a53d4c475f719b88.json"}}, {"family": "Fedorov", "given": "Sergey", "initials": "S", "orcid": "0000-0001-8179-740X", "researcher": {"href": "https://publications.scilifelab.se/researcher/856215bb926b471c9d74e7408715f8e6.json"}}, {"family": "Fiore", "given": "Ivana", "initials": "I", "orcid": "0000-0001-5721-0760", "researcher": {"href": "https://publications.scilifelab.se/researcher/48a313be55974f488d3804f980eb0dd0.json"}}, {"family": "Fulton", "given": "Deirdre", "initials": "D"}, {"family": "Germonpr\u00e9", "given": "Mietje", "initials": "M", "orcid": "0000-0001-8865-0937", "researcher": {"href": "https://publications.scilifelab.se/researcher/79253311b1c64b599c8987b947459391.json"}}, {"family": "Haile", "given": "James", "initials": "J", "orcid": "0000-0002-8521-8337", "researcher": {"href": "https://publications.scilifelab.se/researcher/253913f4bc03438fb7e5c075014d2f6e.json"}}, {"family": "Irving-Pease", "given": "Evan K", "initials": "EK", "orcid": "0000-0003-1940-2192", "researcher": {"href": "https://publications.scilifelab.se/researcher/02e144af5864412baa97c9fa5defbfd5.json"}}, {"family": "Jamieson", "given": "Alexandra", "initials": "A", "orcid": "0000-0003-0979-5762", "researcher": {"href": "https://publications.scilifelab.se/researcher/b70ced169df04e52af5047b555159daf.json"}}, {"family": "Janssens", "given": "Luc", "initials": "L"}, {"family": "Kirillova", "given": "Irina", "initials": "I"}, {"family": "Horwitz", "given": "Liora Kolska", "initials": "LK"}, {"family": "Kuzmanovic-Cvetkovi\u0107", "given": "Julka", "initials": "J"}, {"family": "Kuzmin", "given": "Yaroslav", "initials": "Y", "orcid": "0000-0002-4512-2269", "researcher": {"href": "https://publications.scilifelab.se/researcher/1326bb181c944b00a73d940f87ddf298.json"}}, {"family": "Losey", "given": "Robert J", "initials": "RJ", "orcid": "0000-0003-3615-8160", "researcher": {"href": "https://publications.scilifelab.se/researcher/4fae0ee7f4f24212ba68d26087deaf88.json"}}, {"family": "Dizdar", "given": "Daria Lo\u017enjak", "initials": "DL", "orcid": "0000-0002-5769-2269", "researcher": {"href": "https://publications.scilifelab.se/researcher/bb0100bc6c5d459aa8f9b05b2e236ba5.json"}}, {"family": "Mashkour", "given": "Marjan", "initials": "M", "orcid": "0000-0003-3630-9459", "researcher": {"href": "https://publications.scilifelab.se/researcher/2d45bd37c43f4f7fba2c62c9a26e18c7.json"}}, {"family": "Novak", "given": "Mario", "initials": "M", "orcid": "0000-0002-4567-8742", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae952c508a1d444c9e3ee6cdb0c5a2ae.json"}}, {"family": "Onar", "given": "Vedat", "initials": "V", "orcid": "0000-0002-8359-243X", "researcher": {"href": "https://publications.scilifelab.se/researcher/d129588489cb4684b204c29aba54b1fc.json"}}, {"family": "Orton", "given": "David", "initials": "D", "orcid": "0000-0003-4069-8004", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b0e6ccfd34e49a1878181fa931114de.json"}}, {"family": "Pasari\u0107", "given": "Maja", "initials": "M"}, {"family": "Radivojevi\u0107", "given": "Miljana", "initials": "M", "orcid": "0000-0001-7329-305X", "researcher": {"href": "https://publications.scilifelab.se/researcher/19d71e76741c4d7eacc555b9328291c7.json"}}, {"family": "Rajkovi\u0107", "given": "Dragana", "initials": "D"}, {"family": "Roberts", "given": "Benjamin", "initials": "B"}, {"family": "Ryan", "given": "Hannah", "initials": "H", "orcid": "0000-0002-4320-4594", "researcher": {"href": "https://publications.scilifelab.se/researcher/1a07befb801c478692e3508b663d1a97.json"}}, {"family": "Sablin", "given": "Mikhail", "initials": "M", "orcid": "0000-0002-2773-7454", "researcher": {"href": "https://publications.scilifelab.se/researcher/3355f7b5b291492b8ff2119fd74adbaf.json"}}, {"family": "Shidlovskiy", "given": "Fedor", "initials": "F"}, {"family": "Stojanovi\u0107", "given": "Ivana", "initials": "I", "orcid": "0000-0001-5271-680X", "researcher": {"href": "https://publications.scilifelab.se/researcher/d603204ff3c04194a7246468a9f1754e.json"}}, {"family": "Tagliacozzo", "given": "Antonio", "initials": "A"}, {"family": "Trantalidou", "given": "Katerina", "initials": "K"}, {"family": "Ull\u00e9n", "given": "Inga", "initials": "I"}, {"family": "Villaluenga", "given": "Aritza", "initials": "A"}, {"family": "Wapnish", "given": "Paula", "initials": "P"}, {"family": "Dobney", "given": "Keith", "initials": "K", "orcid": "0000-0001-9036-4681", "researcher": {"href": "https://publications.scilifelab.se/researcher/29ea25869ffa4984a013051452969efb.json"}}, {"family": "G\u00f6therstr\u00f6m", "given": "Anders", "initials": "A", "orcid": "0000-0001-6307-8188", "researcher": {"href": "https://publications.scilifelab.se/researcher/2a1a0a680ab8456cbf5a941e9718fd5a.json"}}, {"family": "Linderholm", "given": "Anna", "initials": "A", "orcid": "0000-0002-1613-9926", "researcher": {"href": "https://publications.scilifelab.se/researcher/27c319330d1e4827858b5612dc203c69.json"}}, {"family": "Dal\u00e9n", "given": "Love", "initials": "L", "orcid": "0000-0001-8270-7613", "researcher": {"href": "https://publications.scilifelab.se/researcher/48ecf726779249ac9d12f4f7a1cc62bf.json"}}, {"family": "Pinhasi", "given": "Ron", "initials": "R", "orcid": "0000-0003-1629-8131", "researcher": {"href": "https://publications.scilifelab.se/researcher/dd8eedf480ae494d9e6249ec58dd1867.json"}}, {"family": "Larson", "given": "Greger", "initials": "G", "orcid": "0000-0002-4092-0392", "researcher": {"href": "https://publications.scilifelab.se/researcher/8313c5d2d5a148349ad14e51deca8ab5.json"}}, {"family": "Skoglund", "given": "Pontus", "initials": "P", "orcid": "0000-0002-3021-5913", "researcher": {"href": "https://publications.scilifelab.se/researcher/338a5f8f37fb48b3887230dfd81786d3.json"}}], "type": "journal article", "published": "2020-10-30", "journal": {"title": "Science", "issn": "1095-9203", "volume": "370", "issue": "6516", "pages": "557-564", "issn-l": "0036-8075"}, "abstract": "Dogs were the first domestic animal, but little is known about their population history and to what extent it was linked to humans. We sequenced 27 ancient dog genomes and found that all dogs share a common ancestry distinct from present-day wolves, with limited gene flow from wolves since domestication but substantial dog-to-wolf gene flow. By 11,000 years ago, at least five major ancestry lineages had diversified, demonstrating a deep genetic history of dogs during the Paleolithic. Coanalysis with human genomes reveals aspects of dog population history that mirror humans, including Levant-related ancestry in Africa and early agricultural Europe. Other aspects differ, including the impacts of steppe pastoralist expansions in West and East Eurasia and a near-complete turnover of Neolithic European dog ancestry.", "doi": "10.1126/science.aba9572", "pmid": "33122379", "labels": {"NGI Stockholm (Genomics Applications)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service"}, "xrefs": [{"db": "pii", "key": "370/6516/557"}, {"db": "pmc", "key": "PMC7116352"}, {"db": "mid", "key": "EMS103415"}], "notes": [], "created": "2021-01-08T16:29:50.956Z", "modified": "2021-11-10T12:45:57.753Z"}, {"entity": "publication", "iuid": "fdff2262424e46cc949c4ce71f7b8f59", "links": {"self": {"href": "https://publications.scilifelab.se/publication/fdff2262424e46cc949c4ce71f7b8f59.json"}, "display": {"href": "https://publications.scilifelab.se/publication/fdff2262424e46cc949c4ce71f7b8f59"}}, "title": "Intra-Individual Behavioural Variability: A Trait under Genetic Control.", "authors": [{"family": "Henriksen", "given": "Rie", "initials": "R"}, {"family": "H\u00f6glund", "given": "Andrey", "initials": "A", "orcid": "0000-0002-1130-374X", "researcher": {"href": "https://publications.scilifelab.se/researcher/70a484451caf40f2a1a196b36bb9c423.json"}}, {"family": "Fogelholm", "given": "Jesper", "initials": "J", "orcid": "0000-0002-0868-8722", "researcher": {"href": "https://publications.scilifelab.se/researcher/5dc8c561c04f437991504aca4c86593d.json"}}, {"family": "Abbey-Lee", "given": "Robin", "initials": "R"}, {"family": "Johnsson", "given": "Martin", "initials": "M"}, {"family": "Dingemanse", "given": "Niels J", "initials": "NJ", "orcid": "0000-0003-3320-0861", "researcher": {"href": "https://publications.scilifelab.se/researcher/364e2f2173244470bc7f9c1feff13bc9.json"}}, {"family": "Wright", "given": "Dominic", "initials": "D", "orcid": "0000-0003-2329-2635", "researcher": {"href": "https://publications.scilifelab.se/researcher/6447b896ea3b453ab10136b5f44ae241.json"}}], "type": "journal article", "published": "2020-10-29", "journal": {"title": "Int J Mol Sci", "issn": "1422-0067", "issn-l": null, "volume": "21", "issue": "21", "pages": "8069"}, "abstract": "When individuals are measured more than once in the same context they do not behave in exactly the same way each time. The degree of predictability differs between individuals, with some individuals showing low levels of variation around their behavioural mean while others show high levels of variation. This intra-individual variability in behaviour has received much less attention than between-individual variability in behaviour, and very little is known about the underlying mechanisms that affect this potentially large but understudied component of behavioural variation. In this study, we combine standardized behavioural tests in a chicken intercross to estimate intra-individual behavioural variability with a large-scale genomics analysis to identify genes affecting intra-individual behavioural variability in an avian population. We used a variety of different anxiety-related behavioural phenotypes for this purpose. Our study shows that intra-individual variability in behaviour has a direct genetic basis that is largely unique compared to the genetic architecture for the standard behavioural measures they are based on (at least in the detected quantitative trait locus). We identify six suggestive candidate genes that may underpin differences in intra-individual behavioural variability, with several of these candidates having previously been linked to behaviour and mental health. These findings demonstrate that intra-individual variability in behaviour appears to be a heritable trait in and of itself on which evolution can act.", "doi": "10.3390/ijms21218069", "pmid": "33138119", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "ijms21218069"}, {"db": "pmc", "key": "PMC7663371"}], "notes": [], "created": "2021-01-12T13:47:04.128Z", "modified": "2024-01-16T13:48:41.496Z"}, {"entity": "publication", "iuid": "16bb63c3f796465f82d6e2b051fffa87", "links": {"self": {"href": "https://publications.scilifelab.se/publication/16bb63c3f796465f82d6e2b051fffa87.json"}, "display": {"href": "https://publications.scilifelab.se/publication/16bb63c3f796465f82d6e2b051fffa87"}}, "title": "Impacts of thermal fluctuations on heat tolerance and its metabolomic basis in Arabidopsis thaliana, Drosophila melanogaster, and Orchesella cincta.", "authors": [{"family": "Noer", "given": "Natasja Krog", "initials": "NK", "orcid": "0000-0002-4430-0342", "researcher": {"href": "https://publications.scilifelab.se/researcher/94c4e99bfcd84fd1a8d17685faacc6f3.json"}}, {"family": "Pagter", "given": "Majken", "initials": "M"}, {"family": "Bahrndorff", "given": "Simon", "initials": "S"}, {"family": "Malmendal", "given": "Anders", "initials": "A"}, {"family": "Kristensen", "given": "Torsten Nygaard", "initials": "TN"}], "type": "journal article", "published": "2020-10-29", "journal": {"title": "PLoS ONE", "issn": "1932-6203", "volume": "15", "issue": "10", "pages": "e0237201", "issn-l": "1932-6203"}, "abstract": "Temperature varies on a daily and seasonal scale and thermal fluctuations are predicted to become even more pronounced under future climate changes. Studies suggest that plastic responses are crucial for species' ability to cope with thermal stress including variability in temperature, but most often laboratory studies on thermal adaptation in plant and ectotherm organisms are performed at constant temperatures and few species included. Recent studies using fluctuating thermal regimes find that thermal performance is affected by both temperature mean and fluctuations, and that plastic responses likely will differ between species according to life strategy and selective past. Here we investigate how acclimation to fluctuating or constant temperature regimes, but with the same mean temperature, impact on heat stress tolerance across a plant (Arabidopsis thaliana) and two arthropod species (Orchesella cincta and Drosophila melanogaster) inhabiting widely different thermal microhabitats and with varying capability for behavioral stress avoidance. Moreover, we investigate the underlying metabolic responses of acclimation using NMR metabolomics. We find increased heat tolerance for D. melanogaster and A. thaliana exposed to fluctuating acclimation temperatures, but not for O. cincta. The response was most pronounced for A. thaliana, which also showed a stronger metabolome response to thermal fluctuations than both arthropods. Generally, sugars were more abundant across A. thaliana and D. melanogaster when exposed to fluctuating compared to constant temperature, whereas amino acids were less abundant. This pattern was not evident for O. cincta, and generally we do not find much evidence for similar metabolomics responses to fluctuating temperature acclimation across species. Differences between the investigated species' ecology and different ability to behaviorally thermoregulate may have shaped their physiological responses to thermal fluctuations.", "doi": "10.1371/journal.pone.0237201", "pmid": "33119606", "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7595314"}, {"db": "pii", "key": "PONE-D-20-22152"}], "notes": [], "created": "2023-05-31T16:22:58.072Z", "modified": "2025-10-17T13:03:56.485Z"}, {"entity": "publication", "iuid": "41bc355c40704d2c82ce195de926f8b9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/41bc355c40704d2c82ce195de926f8b9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/41bc355c40704d2c82ce195de926f8b9"}}, "title": "Horizontal Gene Transfer and Tandem Duplication Shape the Unique CAZyme Complement of the Mycoparasitic Oomycetes Pythium oligandrum and Pythium periplocum.", "authors": [{"family": "Liang", "given": "Dong", "initials": "D"}, {"family": "Andersen", "given": "Christian Benjamin", "initials": "CB"}, {"family": "Vetukuri", "given": "Ramesh R", "initials": "RR"}, {"family": "Dou", "given": "Daolong", "initials": "D"}, {"family": "Grenville-Briggs", "given": "Laura J", "initials": "LJ"}], "type": "journal article", "published": "2020-10-29", "journal": {"title": "Front Microbiol", "issn": "1664-302X", "volume": "11", "issue": null, "pages": "581698", "issn-l": "1664-302X"}, "abstract": "Crop protection strategies that are effective but that reduce our reliance on chemical pesticides are urgently needed to meet the UN sustainable development goals for global food security. Mycoparasitic oomycetes such as Pythium oligandrum and Pythium periplocum, have potential for the biological control of plant diseases that threaten crops and have attracted much attention due to their abilities to antagonize plant pathogens and modulate plant immunity. Studies of the molecular and genetic determinants of mycoparasitism in these species have been less well developed than those of their fungal counterparts. Carbohydrate-active enzymes (CAZymes) from P. oligandrum and P. periplocum are predicted to be important components of mycoparasitism, being involved in the degradation of the cell wall of their oomycete and fungal prey species. To explore the evolution of CAZymes of these species we performed an in silico identification and comparison of the full CAZyme complement (CAZyome) of the two mycoparasitic Pythium species (P. oligandrum and P. periplocum), with seven other Pythium species, and four Phytophthora species. Twenty CAZy gene families involved in the degradation of cellulose, hemicellulose, glucan, and chitin were expanded in, or unique to, mycoparasitic Pythium species and several of these genes were expressed during mycoparasitic interactions with either oomycete or fungal prey, as revealed by RNA sequencing and quantitative qRT-PCR. Genes from three of the cellulose and chitin degrading CAZy families (namely AA9, GH5_14, and GH19) were expanded via tandem duplication and predominantly located in gene sparse regions of the genome, suggesting these enzymes are putative pathogenicity factors able to undergo rapid evolution. In addition, five of the CAZy gene families were likely to have been obtained from other microbes by horizontal gene transfer events. The mycoparasitic species are able to utilize complex carbohydrates present in fungal cell walls, namely chitin and N-acetylglucosamine for growth, in contrast to their phytopathogenic counterparts. Nonetheless, a preference for the utilization of simple sugars for growth appears to be a common trait within the oomycete lineage.", "doi": "10.3389/fmicb.2020.581698", "pmid": "33329445", "labels": {"NGI Stockholm (Genomics Applications)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7720654"}], "notes": [], "created": "2021-01-08T16:30:27.463Z", "modified": "2021-11-10T12:46:01.223Z"}, {"entity": "publication", "iuid": "9e62b2cc7c8f49ee82a29100eaf8594f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9e62b2cc7c8f49ee82a29100eaf8594f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9e62b2cc7c8f49ee82a29100eaf8594f"}}, "title": "DNA methylation in canine brains is related to domestication and dog-breed formation.", "authors": [{"family": "Sundman", "given": "Ann-Sofie", "initials": "AS"}, {"family": "P\u00e9rtille", "given": "F\u00e1bio", "initials": "F", "orcid": "0000-0002-7214-9184", "researcher": {"href": "https://publications.scilifelab.se/researcher/2279c5ebf16f419bab7c3af87bac81d3.json"}}, {"family": "Lehmann Coutinho", "given": "Luiz", "initials": "L"}, {"family": "Jazin", "given": "Elena", "initials": "E"}, {"family": "Guerrero-Bosagna", "given": "Carlos", "initials": "C"}, {"family": "Jensen", "given": "Per", "initials": "P", "orcid": "0000-0001-5491-0649", "researcher": {"href": "https://publications.scilifelab.se/researcher/b83892cd7d6a46898629107a11205254.json"}}], "type": "journal article", "published": "2020-10-29", "journal": {"title": "PLoS ONE", "issn": "1932-6203", "volume": "15", "issue": "10", "pages": "e0240787", "issn-l": "1932-6203"}, "abstract": "Epigenetic factors such as DNA methylation act as mediators in the interaction between genome and environment. Variation in the epigenome can both affect phenotype and be inherited, and epigenetics has been suggested to be an important factor in the evolutionary process. During domestication, dogs have evolved an unprecedented between-breed variation in morphology and behavior in an evolutionary short period. In the present study, we explore DNA methylation differences in brain, the most relevant tissue with respect to behavior, between wolf and dog breeds. We optimized a combined method of genotype-by-sequencing (GBS) and methylated DNA immunoprecipitation (MeDIP) for its application in canines. Genomic DNA from the frontal cortex of 38 dogs of 8 breeds and three wolves was used. GBS and GBS-MeDIP libraries were prepared and sequenced on Illuma HiSeq2500 platform. The reduced sample represented 1.18 \u00b1 0.4% of the total dog genome (2,4 billion BP), while the GBS-MeDIP covered 11,250,788 \u00b1 4,042,106 unique base pairs. We find substantial DNA methylation differences between wolf and dog and between the dog breeds. The methylation profiles of the different groups imply that epigenetic factors may have been important in the speciation from dog to wolf, but also in the divergence of different dog breeds. Specifically, we highlight methylation differences in genes related to behavior and morphology. We hypothesize that these differences are involved in the phenotypic variation found among dogs, whereas future studies will have to find the specific mechanisms. Our results not only add an intriguing new dimension to dog breeding but are also useful to further understanding of epigenetic involvement.", "doi": "10.1371/journal.pone.0240787", "pmid": "33119634", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "PONE-D-20-11468"}, {"db": "pmc", "key": "PMC7595415"}], "notes": [], "created": "2020-11-04T06:05:40.841Z", "modified": "2021-11-10T12:46:05.356Z"}, {"entity": "publication", "iuid": "4c05b1f667444154b6753f7416a7b59a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4c05b1f667444154b6753f7416a7b59a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4c05b1f667444154b6753f7416a7b59a"}}, "title": "Activation of RAS Signalling is Associated with Altered Cell Adhesion in Phaeochromocytoma.", "authors": [{"family": "Rossitti", "given": "Hugo M", "initials": "HM", "orcid": "0000-0002-3766-6258", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae2372259d634006ba294b132d83149e.json"}}, {"family": "Dutta", "given": "Ravi Kumar", "initials": "RK"}, {"family": "Larsson", "given": "Catharina", "initials": "C"}, {"family": "Ghayee", "given": "Hans K", "initials": "HK"}, {"family": "S\u00f6derkvist", "given": "Peter", "initials": "P", "orcid": "0000-0001-9867-8706", "researcher": {"href": "https://publications.scilifelab.se/researcher/c1fc163b9a08421180f7f235af3897f4.json"}}, {"family": "Gimm", "given": "Oliver", "initials": "O", "orcid": "0000-0002-0054-664X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9879641fb40042ae90ff034f4912a16d.json"}}], "type": "journal article", "published": "2020-10-29", "journal": {"title": "Int J Mol Sci", "issn": "1422-0067", "issn-l": null, "volume": "21", "issue": "21", "pages": "8072"}, "abstract": "Phaeochromocytomas and paragangliomas (PPGLs) are neuroendocrine catecholamine-producing tumours that may progress into inoperable metastatic disease. Treatment options for metastatic disease are limited, indicating a need for functional studies to identify pharmacologically targetable pathophysiological mechanisms, which require biologically relevant experimental models. Recently, a human progenitor phaeochromocytoma cell line named \"hPheo1\" was established, but its genotype has not been characterised. Performing exome sequencing analysis, we identified a KIF1B T827I mutation, and the oncogenic NRAS Q61K mutation. While KIF1B mutations are recurring somatic events in PPGLs, NRAS mutations have hitherto not been detected in PPGLs. Therefore, we aimed to assess its implications for the hPheo1 cell line, and possible relevance for the pathophysiology of PPGLs. We found that transient downregulation of NRAS in hPheo1 led to elevated expression of genes associated with cell adhesion, and enhanced adhesion to hPheo1 cells' extracellular matrix. Analyses of previously published mRNA data from two independent PPGL patient cohorts (212 tissue samples) revealed a subcluster of PPGLs featuring hyperactivated RAS pathway-signalling and under-expression of cell adhesion-related gene expression programs. Thus, we conclude that NRAS activity in hPheo1 decreases adhesion to their own extracellular matrix and mirrors a transcriptomic RAS-signalling-related phenomenon in PPGLs.", "doi": "10.3390/ijms21218072", "pmid": "33138083", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "ijms21218072"}, {"db": "pmc", "key": "PMC7663737"}], "notes": [], "created": "2020-12-11T13:37:09.376Z", "modified": "2024-01-16T13:48:41.504Z"}, {"entity": "publication", "iuid": "7799f6442abe4a21905074224e018909", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7799f6442abe4a21905074224e018909.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7799f6442abe4a21905074224e018909"}}, "title": "Nuclear gene proximity and protein interactions shape transcript covariations in mammalian single cells.", "authors": [{"family": "Tarbier", "given": "Marcel", "initials": "M", "orcid": "0000-0003-0556-2531", "researcher": {"href": "https://publications.scilifelab.se/researcher/662e96c24ee6442898ec2caab1eec25d.json"}}, {"family": "Mackowiak", "given": "Sebastian D", "initials": "SD"}, {"family": "Frade", "given": "Jo\u00e3o", "initials": "J", "orcid": "0000-0003-3961-7641", "researcher": {"href": "https://publications.scilifelab.se/researcher/92f0e07be91a4e858100b84a287e133a.json"}}, {"family": "Catuara-Solarz", "given": "Silvina", "initials": "S"}, {"family": "Biryukova", "given": "Inna", "initials": "I", "orcid": "0000-0003-0701-2808", "researcher": {"href": "https://publications.scilifelab.se/researcher/47d787e9d8e14b8fa598d8c3e82e4058.json"}}, {"family": "Gelali", "given": "Eleni", "initials": "E", "orcid": "0000-0003-0067-5473", "researcher": {"href": "https://publications.scilifelab.se/researcher/b1a4d90932dd45509d71a672ec5a12af.json"}}, {"family": "Men\u00e9ndez", "given": "Diego B\u00e1rcena", "initials": "DB"}, {"family": "Zapata", "given": "Luis", "initials": "L", "orcid": "0000-0002-1386-2019", "researcher": {"href": "https://publications.scilifelab.se/researcher/c1e6b01d1d074ce78a9cf40a9560e7fc.json"}}, {"family": "Ossowski", "given": "Stephan", "initials": "S"}, {"family": "Bienko", "given": "Magda", "initials": "M", "orcid": "0000-0002-6499-9082", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a983bc4595448be8b0f7487f17afa7d.json"}}, {"family": "Gallant", "given": "Caroline J", "initials": "CJ"}, {"family": "Friedl\u00e4nder", "given": "Marc R", "initials": "MR", "orcid": "0000-0001-6577-4363", "researcher": {"href": "https://publications.scilifelab.se/researcher/744f7c6d0a884d9daa2e7303ed1779b8.json"}}], "type": "journal article", "published": "2020-10-28", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "11", "issue": "1", "pages": "5445"}, "abstract": "Single-cell RNA sequencing studies on gene co-expression patterns could yield important regulatory and functional insights, but have so far been limited by the confounding effects of differentiation and cell cycle. We apply a tailored experimental design that eliminates these confounders, and report thousands of intrinsically covarying gene pairs in mouse embryonic stem cells. These covariations form a network with biological properties, outlining known and novel gene interactions. We provide the first evidence that miRNAs naturally induce transcriptome-wide covariations and compare the relative importance of nuclear organization, transcriptional and post-transcriptional regulation in defining covariations. We find that nuclear organization has the greatest impact, and that genes encoding for physically interacting proteins specifically tend to covary, suggesting importance for protein complex formation. Our results lend support to the concept of post-transcriptional RNA operons, but we further present evidence that nuclear proximity of genes may provide substantial functional regulation in mammalian single cells.", "doi": "10.1038/s41467-020-19011-5", "pmid": "33116115", "labels": {"Eukaryotic Single Cell Genomics (ESCG)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-19011-5"}, {"db": "pmc", "key": "PMC7595044"}], "notes": [], "created": "2021-01-11T11:38:53.729Z", "modified": "2024-01-16T13:48:41.524Z"}, {"entity": "publication", "iuid": "889f5ed4ead54d3c9a1615ea937c77fb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/889f5ed4ead54d3c9a1615ea937c77fb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/889f5ed4ead54d3c9a1615ea937c77fb"}}, "title": "Microbiomes in a manganese oxide producing ecosystem in the Ytterby mine, Sweden: impact on metal mobility.", "authors": [{"family": "Sj\u00f6berg", "given": "Susanne", "initials": "S"}, {"family": "Stairs", "given": "Courtney W", "initials": "CW"}, {"family": "Allard", "given": "Bert", "initials": "B"}, {"family": "Homa", "given": "Felix", "initials": "F"}, {"family": "Martin", "given": "Tom", "initials": "T"}, {"family": "Sj\u00f6berg", "given": "Viktor", "initials": "V"}, {"family": "Ettema", "given": "Thijs J G", "initials": "TJG"}, {"family": "Dupraz", "given": "Christophe", "initials": "C"}], "type": "journal article", "published": "2020-10-28", "journal": {"title": "FEMS Microbiol. Ecol.", "issn": "1574-6941", "issn-l": "0168-6496", "volume": "96", "issue": "11", "pages": null}, "abstract": "Microbe-mediated precipitation of Mn-oxides enriched in rare earth elements (REE) and other trace elements was discovered in tunnels leading to the main shaft of the Ytterby mine, Sweden. Defining the spatial distribution of microorganisms and elements in this ecosystem provide a better understanding of specific niches and parameters driving the emergence of these communities and associated mineral precipitates. Along with elemental analyses, high-throughput sequencing of the following four subsystems were conducted: (i) water seeping from a rock fracture into the tunnel, (ii) Mn-oxides and associated biofilm; referred to as the Ytterby Black Substance (YBS) biofilm (iii) biofilm forming bubbles on the Mn-oxides; referred to as the bubble biofilm and (iv) fracture water that has passed through the biofilms. Each subsystem hosts a specific collection of microorganisms. Differentially abundant bacteria in the YBS biofilm were identified within the Rhizobiales (e.g. Pedomicrobium), PLTA13 Gammaproteobacteria, Pirellulaceae, Hyphomonadaceae, Blastocatellia and Nitrospira. These taxa, likely driving the Mn-oxide production, were not detected in the fracture water. This biofilm binds Mn, REE and other trace elements in an efficient, dynamic process, as indicated by substantial depletion of these metals from the fracture water as it passes through the Mn deposit zone. Microbe-mediated oxidation of Mn(II) and formation of Mn(III/IV)-oxides can thus have considerable local environmental impact by removing metals from aquatic environments.", "doi": "10.1093/femsec/fiaa169", "pmid": "32815988", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "5894917"}, {"db": "pmc", "key": "PMC7593233"}], "notes": [], "created": "2020-12-08T23:17:35.910Z", "modified": "2021-11-10T12:46:08.740Z"}, {"entity": "publication", "iuid": "61faf99df7d143678abba24c31bdb534", "links": {"self": {"href": "https://publications.scilifelab.se/publication/61faf99df7d143678abba24c31bdb534.json"}, "display": {"href": "https://publications.scilifelab.se/publication/61faf99df7d143678abba24c31bdb534"}}, "title": "Population genomics reveals lack of greater white-fronted introgression into the Swedish lesser white-fronted goose.", "authors": [{"family": "D\u00edez-Del-Molino", "given": "David", "initials": "D"}, {"family": "von Seth", "given": "Johanna", "initials": "J"}, {"family": "Gyllenstrand", "given": "Niclas", "initials": "N"}, {"family": "Widemo", "given": "Fredrik", "initials": "F"}, {"family": "Liljeb\u00e4ck", "given": "Niklas", "initials": "N"}, {"family": "Svensson", "given": "Mikael", "initials": "M"}, {"family": "Sj\u00f6gren-Gulve", "given": "Per", "initials": "P"}, {"family": "Dal\u00e9n", "given": "Love", "initials": "L", "orcid": "0000-0001-8270-7613", "researcher": {"href": "https://publications.scilifelab.se/researcher/48ecf726779249ac9d12f4f7a1cc62bf.json"}}], "type": "journal article", "published": "2020-10-27", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "18347", "issn-l": "2045-2322"}, "abstract": "Interspecific introgression is considered a potential threat to endangered taxa. One example where this has had a major impact on conservation policy is the lesser white-fronted goose (LWfG). After a dramatic decline in Sweden, captive breeding birds were released between 1981-1999 with the aim to reinforce the population. However, the detection of greater white-fronted goose (GWfG) mitochondrial DNA in the LWfG breeding stock led to the release program being dismantled, even though the presence of GWfG introgression in the actual wild Swedish LWfG population was never documented. To examine this, we sequenced the complete genomes of 21 LWfG birds from the Swedish, Russian and Norwegian populations, and compared these with genomes from other goose species, including the GWfG. We found no evidence of interspecific introgression into the wild Swedish LWfG population in either nuclear genomic or mitochondrial data. Moreover, Swedish LWfG birds are genetically distinct from the Russian and Norwegian populations and display comparatively low genomic diversity and high levels of inbreeding. Our findings highlight the utility of genomic approaches in providing scientific evidence that can help improve conservation management as well as policies for breeding and reinforcement programmes.", "doi": "10.1038/s41598-020-75315-y", "pmid": "33110153", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-75315-y"}, {"db": "pmc", "key": "PMC7591532"}], "notes": [], "created": "2020-12-07T16:34:43.881Z", "modified": "2024-01-16T13:48:41.531Z"}, {"entity": "publication", "iuid": "7996780e07c04e949fd225c2a80edf09", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7996780e07c04e949fd225c2a80edf09.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7996780e07c04e949fd225c2a80edf09"}}, "title": "ENPL-1, the Caenorhabditis elegans homolog of GRP94, promotes insulin secretion via regulation of proinsulin processing and maturation.", "authors": [{"family": "Podraza-Farhanieh", "given": "Agnieszka", "initials": "A", "orcid": "0000-0002-1120-8216", "researcher": {"href": "https://publications.scilifelab.se/researcher/8244c5dad7974bc0a2a4ec38cc3e58ce.json"}}, {"family": "Natarajan", "given": "Balasubramanian", "initials": "B", "orcid": "0000-0003-2371-0550", "researcher": {"href": "https://publications.scilifelab.se/researcher/3ca28d7e37654cd0a4b497d7a0d72b4e.json"}}, {"family": "Raj", "given": "Dorota", "initials": "D", "orcid": "0000-0002-7357-2902", "researcher": {"href": "https://publications.scilifelab.se/researcher/23ff7c388c2b43e3a9d3a3514fe5e049.json"}}, {"family": "Kao", "given": "Gautam", "initials": "G", "orcid": "0000-0003-1313-3024", "researcher": {"href": "https://publications.scilifelab.se/researcher/4575b678a90740428136c9f5e1bdd53b.json"}}, {"family": "Naredi", "given": "Peter", "initials": "P", "orcid": "0000-0002-5652-0422", "researcher": {"href": "https://publications.scilifelab.se/researcher/a41ccd84008a4a94a29410451bc012c9.json"}}], "type": "journal article", "published": "2020-10-27", "journal": {"title": "Development", "issn": "1477-9129", "volume": "147", "issue": "20", "issn-l": "0950-1991"}, "abstract": "Insulin/IGF signaling in Caenorhabditis elegans is crucial for proper development of the dauer larva and growth control. Mutants disturbing insulin processing, secretion and downstream signaling perturb this process and have helped identify genes that affect progression of type 2 diabetes. Insulin maturation is required for its proper secretion by pancreatic \u03b2 cells. The role of the endoplasmic reticulum (ER) chaperones in insulin processing and secretion needs further study. We show that the C. elegans ER chaperone ENPL-1/GRP94 (HSP90B1), acts in dauer development by promoting insulin secretion and signaling. Processing of a proinsulin likely involves binding between the two proteins via a specific domain. We show that, in enpl-1 mutants, an unprocessed insulin exits the ER lumen and is found in dense core vesicles, but is not secreted. The high ER stress in enpl-1 mutants does not cause the secretion defect. Importantly, increased ENPL-1 levels result in increased secretion. Taken together, our work indicates that ENPL-1 operates at the level of insulin availability and is an essential modulator of insulin processing and secretion.", "doi": "10.1242/dev.190082", "pmid": "33037039", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "dev.190082"}], "notes": [], "created": "2023-02-16T08:08:41.919Z", "modified": "2023-02-16T08:08:42.245Z"}, {"entity": "publication", "iuid": "c872c51986274d1290e3f3a1a5f68ddc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c872c51986274d1290e3f3a1a5f68ddc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c872c51986274d1290e3f3a1a5f68ddc"}}, "title": "Developmental and MAPK-responsive transcription factors drive distinct malignant subtypes and genetic dependencies in pancreatic cancer", "authors": [{"family": "Laise", "given": "Pasquale", "initials": "P", "orcid": "0000-0003-1469-4704", "researcher": {"href": "https://publications.scilifelab.se/researcher/0592a382bfcf4f2d83e5d79f89bb425a.json"}}, {"family": "Turunen", "given": "Mikko", "initials": "M", "orcid": "0000-0001-5134-1559", "researcher": {"href": "https://publications.scilifelab.se/researcher/c6f360468c4f4329b59de43f4d8eff27.json"}}, {"family": "Garcia", "given": "Alvaro Curiel", "initials": "AC"}, {"family": "Tomassoni", "given": "Lorenzo", "initials": "L"}, {"family": "Maurer", "given": "H Carlo", "initials": "HC", "orcid": "0000-0002-2193-6014", "researcher": {"href": "https://publications.scilifelab.se/researcher/48cde5fef80c4b0e917707ba825b8143.json"}}, {"family": "Elyada", "given": "Ela", "initials": "E"}, {"family": "Schmierer", "given": "Bernhard", "initials": "B", "orcid": "0000-0002-9082-7022", "researcher": {"href": "https://publications.scilifelab.se/researcher/d3ee96f9eb454850be6db3318b28479f.json"}}, {"family": "Worley", "given": "Jeremy", "initials": "J", "orcid": "0000-0003-4517-7080", "researcher": {"href": "https://publications.scilifelab.se/researcher/ba8e8bccdd304afe8ac772f533c75e09.json"}}, {"family": "Kesner", "given": "Jordan", "initials": "J"}, {"family": "Tan", "given": "Xiangtian", "initials": "X"}, {"family": "Fernandez", "given": "Ester Calvo", "initials": "EC"}, {"family": "Wong", "given": "Kelly", "initials": "K"}, {"family": "Wasko", "given": "Urszula N", "initials": "UN"}, {"family": "Tagore", "given": "Somnath", "initials": "S", "orcid": "0000-0003-4742-3679", "researcher": {"href": "https://publications.scilifelab.se/researcher/4aeec80fda63405eaab09827e3f9b704.json"}}, {"family": "Wang", "given": "Alexander L E", "initials": "ALE"}, {"family": "Ge", "given": "Sabrina", "initials": "S"}, {"family": "Iuga", "given": "Alina C", "initials": "AC"}, {"family": "Griffin", "given": "Aaron", "initials": "A"}, {"family": "Wong", "given": "Winston", "initials": "W"}, {"family": "Manji", "given": "Gulam A", "initials": "GA"}, {"family": "Alvarez", "given": "Mariano J", "initials": "MJ", "orcid": "0000-0002-7503-2491", "researcher": {"href": "https://publications.scilifelab.se/researcher/87c7e5b525ad44f4859b434c85ebe066.json"}}, {"family": "Notta", "given": "Faiyaz", "initials": "F", "orcid": "0000-0002-5748-3985", "researcher": {"href": "https://publications.scilifelab.se/researcher/82840ed4e5294488bc9732dcd4fdc36c.json"}}, {"family": "Tuveson", "given": "David A", "initials": "DA"}, {"family": "Olive", "given": "Kenneth P", "initials": "KP", "orcid": "0000-0002-3392-8994", "researcher": {"href": "https://publications.scilifelab.se/researcher/23f056db63144804b1df283e9f5335d3.json"}}, {"family": "Califano", "given": "Andrea", "initials": "A", "orcid": "0000-0003-4742-3679", "researcher": {"href": "https://publications.scilifelab.se/researcher/4aeec80fda63405eaab09827e3f9b704.json"}}], "type": "posted-content", "published": "2020-10-27", "journal": {"title": "biorxiv", "issn": null, "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": null, "doi": "10.1101/2020.10.27.357269", "pmid": null, "labels": {"CRISPR Functional Genomics": "Service"}, "xrefs": [], "notes": [], "created": "2022-11-20T14:20:28.407Z", "modified": "2025-12-18T20:06:18.861Z"}, {"entity": "publication", "iuid": "8ac16f66ce7945b797c3690519c8e15e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8ac16f66ce7945b797c3690519c8e15e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8ac16f66ce7945b797c3690519c8e15e"}}, "title": "Coupling stabilizers open KV1-type potassium channels.", "authors": [{"family": "Silver\u00e5 Ejneby", "given": "Malin", "initials": "M"}, {"family": "Wallner", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Elinder", "given": "Fredrik", "initials": "F"}], "type": "journal article", "published": "2020-10-27", "journal": {"title": "Proc. Natl. Acad. Sci. U.S.A.", "issn": "1091-6490", "volume": "117", "issue": "43", "pages": "27016-27021", "issn-l": "0027-8424"}, "abstract": "The opening and closing of voltage-gated ion channels are regulated by voltage sensors coupled to a gate that controls the ion flux across the cellular membrane. Modulation of any part of gating constitutes an entry point for pharmacologically regulating channel function. Here, we report on the discovery of a large family of warfarin-like compounds that open the two voltage-gated type 1 potassium (KV1) channels KV1.5 and Shaker, but not the related KV2-, KV4-, or KV7-type channels. These negatively charged compounds bind in the open state to positively charged arginines and lysines between the intracellular ends of the voltage-sensor domains and the pore domain. This mechanism of action resembles that of endogenous channel-opening lipids and opens up an avenue for the development of ion-channel modulators.", "doi": "10.1073/pnas.2007965117", "pmid": "33051293", "labels": {"Chemical Biology Consortium Sweden": "Service"}, "xrefs": [{"db": "pii", "key": "2007965117"}, {"db": "pmc", "key": "PMC7604479"}], "notes": [], "created": "2020-11-08T14:40:45.864Z", "modified": "2025-10-17T13:04:28.239Z"}, {"entity": "publication", "iuid": "c46844a0633944c99b1408c2c833442e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c46844a0633944c99b1408c2c833442e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c46844a0633944c99b1408c2c833442e"}}, "title": "UvrD helicase-RNA polymerase interactions are governed by UvrD's carboxy-terminal Tudor domain.", "authors": [{"family": "Kawale", "given": "Ashish A", "initials": "AA", "orcid": "0000-0002-5074-680X", "researcher": {"href": "https://publications.scilifelab.se/researcher/b286129785b441c793dc1ba8f1d09dd2.json"}}, {"family": "Burmann", "given": "Bj\u00f6rn M", "initials": "BM", "orcid": "0000-0002-3135-7964", "researcher": {"href": "https://publications.scilifelab.se/researcher/b7a6d61fc1a64677874973c3247b1eb4.json"}}], "type": "journal article", "published": "2020-10-23", "journal": {"title": "Commun Biol", "issn": "2399-3642", "volume": "3", "issue": "1", "pages": "607", "issn-l": "2399-3642"}, "abstract": "All living organisms have to cope with the constant threat of genome damage by UV light and other toxic reagents. To maintain the integrity of their genomes, organisms developed a variety of DNA repair pathways. One of these, the Transcription Coupled DNA-Repair (TCR) pathway, is triggered by stalled RNA Polymerase (RNAP) complexes at DNA damage sites on actively transcribed genes. A recently elucidated bacterial TCR pathway employs the UvrD helicase pulling back stalled RNAP complexes from the damage, stimulating recruitment of the DNA-repair machinery. However, structural and functional aspects of UvrD's interaction with RNA Polymerase remain elusive. Here we used advanced solution NMR spectroscopy to investigate UvrD's role within the TCR, identifying that the carboxy-terminal region of the UvrD helicase facilitates RNAP interactions by adopting a Tudor-domain like fold. Subsequently, we functionally analyzed this domain, identifying it as a crucial component for the UvrD-RNAP interaction besides having nucleic-acid affinity.", "doi": "10.1038/s42003-020-01332-2", "pmid": "33097771", "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s42003-020-01332-2"}, {"db": "pmc", "key": "PMC7585439"}], "notes": [], "created": "2020-12-11T09:10:27.274Z", "modified": "2025-10-17T13:03:56.528Z"}, {"entity": "publication", "iuid": "13b50e6dabb34ef58cf5cc56f7fc51d3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/13b50e6dabb34ef58cf5cc56f7fc51d3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/13b50e6dabb34ef58cf5cc56f7fc51d3"}}, "title": "Type III ATP synthase is a symmetry-deviated dimer that induces membrane curvature through tetramerization.", "authors": [{"family": "Flygaard", "given": "Rasmus Kock", "initials": "RK", "orcid": "0000-0002-4918-6438", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a5982a29fb44d6b96d84834275b5bd0.json"}}, {"family": "M\u00fchleip", "given": "Alexander", "initials": "A", "orcid": "0000-0002-1877-2282", "researcher": {"href": "https://publications.scilifelab.se/researcher/921b5acb5b7c402fa06c8c148cbd5340.json"}}, {"family": "Tobiasson", "given": "Victor", "initials": "V", "orcid": "0000-0001-8920-017X", "researcher": {"href": "https://publications.scilifelab.se/researcher/5208789057a94d0d9575476bf9c88d5a.json"}}, {"family": "Amunts", "given": "Alexey", "initials": "A", "orcid": "0000-0002-5302-1740", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7d0bf36ad1a47f5b5b88f78d1e15395.json"}}], "type": "journal article", "published": "2020-10-22", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "11", "issue": "1", "pages": "5342", "issn-l": "2041-1723"}, "abstract": "Mitochondrial ATP synthases form functional homodimers to induce cristae curvature that is a universal property of mitochondria. To expand on the understanding of this fundamental phenomenon, we characterized the unique type III mitochondrial ATP synthase in its dimeric and tetrameric form. The cryo-EM structure of a ciliate ATP synthase dimer reveals an unusual U-shaped assembly of 81 proteins, including a substoichiometrically bound ATPTT2, 40 lipids, and co-factors NAD and CoQ. A single copy of subunit ATPTT2 functions as a membrane anchor for the dimeric inhibitor IF1. Type III specific linker proteins stably tie the ATP synthase monomers in parallel to each other. The intricate dimer architecture is scaffolded by an extended subunit-a that provides a template for both intra- and inter-dimer interactions. The latter results in the formation of tetramer assemblies, the membrane part of which we determined to 3.1 \u00c5 resolution. The structure of the type III ATP synthase tetramer and its associated lipids suggests that it is the intact unit propagating the membrane curvature.", "doi": "10.1038/s41467-020-18993-6", "pmid": "33093501", "labels": {"Cryo-EM": "Service", "Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-18993-6"}, {"db": "pmc", "key": "PMC7583250"}], "notes": [], "created": "2020-10-26T14:40:56.262Z", "modified": "2023-12-04T10:09:34.900Z"}, {"entity": "publication", "iuid": "3d6084989c4c436bb04585ec88b5f5f5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3d6084989c4c436bb04585ec88b5f5f5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3d6084989c4c436bb04585ec88b5f5f5"}}, "title": "Polycomb Repressive Complex 2-mediated histone modification H3K27me3 is associated with embryogenic potential in Norway spruce.", "authors": [{"family": "Nakamura", "given": "Miyuki", "initials": "M", "orcid": "0000-0002-8153-7293", "researcher": {"href": "https://publications.scilifelab.se/researcher/fa9f227109b54fa9a1457a1f7af197af.json"}}, {"family": "Batista", "given": "Rita A", "initials": "RA"}, {"family": "K\u00f6hler", "given": "Claudia", "initials": "C", "orcid": "0000-0002-2619-4857", "researcher": {"href": "https://publications.scilifelab.se/researcher/accd3f9307614c8ab67154dd5e50cdac.json"}}, {"family": "Hennig", "given": "Lars", "initials": "L", "orcid": "0000-0002-6645-1862", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b350e5d9ba74c27bf1709ff0457e605.json"}}], "type": "journal article", "published": "2020-10-22", "journal": {"title": "J. Exp. Bot.", "issn": "1460-2431", "volume": "71", "issue": "20", "pages": "6366-6378", "issn-l": "0022-0957"}, "abstract": "Epigenetic reprogramming during germ cell formation is essential to gain pluripotency and thus embryogenic potential. The histone modification H3K27me3, which is catalysed by the Polycomb repressive complex 2 (PRC2), regulates important developmental processes in both plants and animals, and defects in PRC2 components cause pleiotropic developmental abnormalities. Nevertheless, the role of H3K27me3 in determining embryogenic potential in gymnosperms is still elusive. To address this, we generated H3K27me3 profiles of Norway spruce (Picea abies) embryonic callus and non-embryogenic callus using CUT&RUN, which is a powerful method for chromatin profiling. Here, we show that H3K27me3 mainly accumulated in genic regions in the Norway spruce genome, similarly to what is observed in other plant species. Interestingly, H3K27me3 levels in embryonic callus were much lower than those in the other examined tissues, but markedly increased upon embryo induction. These results show that H3K27me3 levels are associated with the embryogenic potential of a given tissue, and that the early phase of somatic embryogenesis is accompanied by changes in H3K27me3 levels. Thus, our study provides novel insights into the role of this epigenetic mark in spruce embryogenesis and reinforces the importance of PRC2 as a key regulator of cell fate determination across different plant species.", "doi": "10.1093/jxb/eraa365", "pmid": "32894759", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "5902563"}, {"db": "pmc", "key": "PMC7586741"}], "notes": [], "created": "2020-11-16T09:34:27.793Z", "modified": "2021-11-10T12:46:16.725Z"}, {"entity": "publication", "iuid": "98c56bf4a6f549c0895f3cef98a9f04d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/98c56bf4a6f549c0895f3cef98a9f04d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/98c56bf4a6f549c0895f3cef98a9f04d"}}, "title": "Genetic Variants Associated with Non-Alcoholic Fatty Liver Disease Do Not Associate with Measures of Sub-Clinical Atherosclerosis: Results from the IMPROVE Study.", "authors": [{"family": "Castaldo", "given": "Luigi", "initials": "L", "orcid": "0000-0001-6883-9396", "researcher": {"href": "https://publications.scilifelab.se/researcher/2e444841bc62402e82952cc4d24be1b9.json"}}, {"family": "Laguzzi", "given": "Federica", "initials": "F"}, {"family": "Strawbridge", "given": "Rona J", "initials": "RJ", "orcid": "0000-0001-8506-3585", "researcher": {"href": "https://publications.scilifelab.se/researcher/8ac5060a3b37466dae002d4ad8f4d0ac.json"}}, {"family": "Baldassarre", "given": "Damiano", "initials": "D"}, {"family": "Veglia", "given": "Fabrizio", "initials": "F", "orcid": "0000-0002-9378-8874", "researcher": {"href": "https://publications.scilifelab.se/researcher/46cd876aad8b495d982cf2a3ac7bb6aa.json"}}, {"family": "Vigo", "given": "Lorenzo", "initials": "L"}, {"family": "Tremoli", "given": "Elena", "initials": "E"}, {"family": "de Faire", "given": "Ulf", "initials": "U"}, {"family": "Eriksson", "given": "Per", "initials": "P"}, {"family": "Smit", "given": "Andries J", "initials": "AJ"}, {"family": "Aubrecht", "given": "Jiri", "initials": "J"}, {"family": "Leander", "given": "Karin", "initials": "K"}, {"family": "Pirro", "given": "Matteo", "initials": "M"}, {"family": "Giral", "given": "Philippe", "initials": "P"}, {"family": "Ritieni", "given": "Alberto", "initials": "A", "orcid": "0000-0003-0314-8839", "researcher": {"href": "https://publications.scilifelab.se/researcher/920e6797a9ac4ea088cd481b11e85a7f.json"}}, {"family": "Di Minno", "given": "Giovanni", "initials": "G"}, {"family": "M\u00e4larstig", "given": "Anders", "initials": "A", "orcid": "0000-0003-2608-1358", "researcher": {"href": "https://publications.scilifelab.se/researcher/e70c845d32264b448e0b4631b826be6d.json"}}, {"family": "Gigante", "given": "Bruna", "initials": "B"}], "type": "journal article", "published": "2020-10-22", "journal": {"title": "Genes", "issn": "2073-4425", "volume": "11", "issue": "11", "pages": "1243", "issn-l": "2073-4425"}, "abstract": "Non-alcoholic fatty liver disease (NAFLD) and atherosclerosis-related cardiovascular diseases (CVD) share common metabolic pathways. We explored the association between three NAFLD-associated single nucleotide polymorphisms (SNPs) rs738409, rs10401969, and rs1260326 with sub-clinical atherosclerosis estimated by the carotid intima-media thickness (c-IMT) and the inter-adventitia common carotid artery diameter (ICCAD) in patients free from clinically overt NAFLD and CVD. The study population is the IMPROVE, a multicenter European study (n = 3711). C-IMT measures and ICCAD were recorded using a standardized protocol. Linear regression with an additive genetic model was used to test for association of the three SNPs with c-IMT and ICCAD. In secondary analyses, the association of the three SNPs with c-IMT and ICCAD was tested after stratification by alanine aminotransferase levels (ALT). No associations were found between rs738409, rs1260326, rs10401969, and c-IMT or ICCAD. Rs738409-G and rs10401969-C were associated with ALT levels (p < 0.001). In patients with ALT levels above 28 U/L (highest quartile), we observed an association between rs10401969-C and c-IMT measures of c-IMTmax and c-IMTmean-max (p = 0.018 and 0.021, respectively). In conclusion, NAFLD-associated SNPs do not associate with sub-clinical atherosclerosis measures. However, our results suggest a possible mediating function of impaired liver function on atherosclerosis development.", "doi": "10.3390/genes11111243", "pmid": "33105679", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "genes11111243"}, {"db": "pmc", "key": "PMC7690395"}], "notes": [], "created": "2020-11-05T14:07:51.289Z", "modified": "2021-11-10T12:46:17.904Z"}, {"entity": "publication", "iuid": "81637524a179454eacfeca141c6eac13", "links": {"self": {"href": "https://publications.scilifelab.se/publication/81637524a179454eacfeca141c6eac13.json"}, "display": {"href": "https://publications.scilifelab.se/publication/81637524a179454eacfeca141c6eac13"}}, "title": "Epigenetic alterations in skin homing CD4+CLA+ T cells of atopic dermatitis patients.", "authors": [{"family": "Acevedo", "given": "Nathalie", "initials": "N"}, {"family": "Benfeitas", "given": "Rui", "initials": "R"}, {"family": "Katayama", "given": "Shintaro", "initials": "S"}, {"family": "Bruhn", "given": "S\u00f6ren", "initials": "S"}, {"family": "Andersson", "given": "Anna", "initials": "A"}, {"family": "Wikberg", "given": "Gustav", "initials": "G"}, {"family": "Lundeberg", "given": "Lena", "initials": "L"}, {"family": "Lindvall", "given": "Jessica M", "initials": "JM", "orcid": "0000-0002-5042-8481", "researcher": {"href": "https://publications.scilifelab.se/researcher/78debae1bc714b11a97ecf9e9656f1eb.json"}}, {"family": "Greco", "given": "Dario", "initials": "D"}, {"family": "Kere", "given": "Juha", "initials": "J"}, {"family": "S\u00f6derh\u00e4ll", "given": "Cilla", "initials": "C"}, {"family": "Scheynius", "given": "Annika", "initials": "A"}], "type": "journal article", "published": "2020-10-22", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "18020", "issn-l": "2045-2322"}, "abstract": "T cells expressing the cutaneous lymphocyte antigen (CLA) mediate pathogenic inflammation in atopic dermatitis (AD). The molecular alterations contributing to their dysregulation remain unclear. With the aim to elucidate putative altered pathways in AD we profiled DNA methylation levels and miRNA expression in sorted T cell populations (CD4+, CD4+CD45RA+ na\u00efve, CD4+CLA+, and CD8+) from adult AD patients and healthy controls (HC). Skin homing CD4+CLA+ T cells from AD patients showed significant differences in DNA methylation in 40 genes compared to HC (p < 0.05). Reduced DNA methylation levels in the upstream region of the interleukin-13 gene (IL13) in CD4+CLA+ T cells from AD patients correlated with increased IL13 mRNA expression in these cells. Sixteen miRNAs showed differential expression in CD4+CLA+ T cells from AD patients targeting genes in 202 biological processes (p < 0.05). An integrated network analysis of miRNAs and CpG sites identified two communities of strongly interconnected regulatory elements with strong antagonistic behaviours that recapitulated the differences between AD patients and HC. Functional analysis of the genes linked to these communities revealed their association with key cytokine signaling pathways, MAP kinase signaling and protein ubiquitination. Our findings support that epigenetic mechanisms play a role in the pathogenesis of AD by affecting inflammatory signaling molecules in skin homing CD4+CLA+ T cells and uncover putative molecules participating in AD pathways.", "doi": "10.1038/s41598-020-74798-z", "pmid": "33093567", "labels": {"Bioinformatics Support, Infrastructure and Training": null, "Bioinformatics Support and Infrastructure": null, "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": null}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-74798-z"}, {"db": "pmc", "key": "PMC7582180"}], "notes": [], "created": "2020-10-26T09:04:32.192Z", "modified": "2024-01-16T13:48:41.543Z"}, {"entity": "publication", "iuid": "68d1db6a6f0c49bb8b5b9b66b2987c50", "links": {"self": {"href": "https://publications.scilifelab.se/publication/68d1db6a6f0c49bb8b5b9b66b2987c50.json"}, "display": {"href": "https://publications.scilifelab.se/publication/68d1db6a6f0c49bb8b5b9b66b2987c50"}}, "title": "Clarithromycin Exerts an Antibiofilm Effect against Salmonella enterica Serovar Typhimurium rdar Biofilm Formation and Transforms the Physiology towards an Apparent Oxygen-Depleted Energy and Carbon Metabolism.", "authors": [{"family": "Zafar", "given": "Munirah", "initials": "M"}, {"family": "Jahan", "given": "Humera", "initials": "H", "orcid": "0000-0003-1219-2970", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d5ffbdc06ad481384145eb57baa263c.json"}}, {"family": "Shafeeq", "given": "Sulman", "initials": "S", "orcid": "0000-0003-1152-526X", "researcher": {"href": "https://publications.scilifelab.se/researcher/e86a079677ae47dc9a6bc423dba02515.json"}}, {"family": "Nimtz", "given": "Manfred", "initials": "M", "orcid": "0000-0002-5798-3592", "researcher": {"href": "https://publications.scilifelab.se/researcher/9be53dd805bd4300b25025d63a396635.json"}}, {"family": "J\u00e4nsch", "given": "Lothar", "initials": "L", "orcid": "0000-0002-5655-1181", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ffcd0acafff4e09aff19ae0c1b801e1.json"}}, {"family": "R\u00f6mling", "given": "Ute", "initials": "U", "orcid": "0000-0003-3812-6621", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a59ac735d61485aa43ee7a2ae3a526d.json"}}, {"family": "Choudhary", "given": "M Iqbal", "initials": "MI", "orcid": "0000-0001-5356-3585", "researcher": {"href": "https://publications.scilifelab.se/researcher/21d3b7d783f548d792692fb24abe60d5.json"}}], "type": "journal article", "published": "2020-10-19", "journal": {"title": "Infect. Immun.", "issn": "1098-5522", "volume": "88", "issue": "11", "issn-l": "0019-9567"}, "abstract": "Upon biofilm formation, production of extracellular matrix components and alteration in physiology and metabolism allows bacteria to build up multicellular communities which can facilitate nutrient acquisition during unfavorable conditions and provide protection toward various forms of environmental stresses to individual cells. Thus, bacterial cells within biofilms become tolerant against antimicrobials and the immune system. In the present study, we evaluated the antibiofilm activity of the macrolides clarithromycin and azithromycin. Clarithromycin showed antibiofilm activity against rdar (red, dry, and rough) biofilm formation of the gastrointestinal pathogen Salmonella enterica serovar Typhimurium ATCC 14028 (Nalr) at a 1.56 \u03bcM subinhibitory concentration in standing culture and dissolved cell aggregates at 15 \u03bcM in a microaerophilic environment, suggesting that the oxygen level affects the activity of the drug. Treatment with clarithromycin significantly decreased transcription and production of the rdar biofilm activator CsgD, with biofilm genes such as csgB and adrA to be concomitantly downregulated. Although fliA and other flagellar regulon genes were upregulated, apparent motility was downregulated. RNA sequencing showed a holistic cell response upon clarithromycin exposure, whereby not only genes involved in the biofilm-related regulatory pathways but also genes that likely contribute to intrinsic antimicrobial resistance, and the heat shock stress response were differentially regulated. Most significantly, clarithromycin exposure shifted the cells toward an apparent oxygen- and energy-depleted status, whereby the metabolism that channels into oxidative phosphorylation was downregulated, and energy gain by degradation of propane 1,2-diol, ethanolamine and l-arginine catabolism, potentially also to prevent cytosolic acidification, was upregulated. This analysis will allow the subsequent identification of novel intrinsic antimicrobial resistance determinants.", "doi": "10.1128/IAI.00510-20", "pmid": "32839186", "labels": {"Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pii", "key": "IAI.00510-20"}, {"db": "pmc", "key": "PMC7573439"}], "notes": [], "created": "2022-03-29T12:54:01.486Z", "modified": "2022-03-29T12:54:01.693Z"}, {"entity": "publication", "iuid": "eb542f0c8e904bd687fcec6c03eed0d5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/eb542f0c8e904bd687fcec6c03eed0d5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/eb542f0c8e904bd687fcec6c03eed0d5"}}, "title": "Automated identification of the mouse brain's spatial compartments from in situ sequencing data.", "authors": [{"family": "Partel", "given": "Gabriele", "initials": "G", "orcid": "0000-0002-4482-3119", "researcher": {"href": "https://publications.scilifelab.se/researcher/cca1e7c3e70a4d45aacc3a46d14b9cbe.json"}}, {"family": "Hilscher", "given": "Markus M", "initials": "MM"}, {"family": "Milli", "given": "Giorgia", "initials": "G"}, {"family": "Solorzano", "given": "Leslie", "initials": "L"}, {"family": "Klemm", "given": "Anna H", "initials": "AH", "orcid": "0000-0002-3466-1320", "researcher": {"href": "https://publications.scilifelab.se/researcher/4ae78afb2a424b0ab70d49871f361d13.json"}}, {"family": "Nilsson", "given": "Mats", "initials": "M", "orcid": "0000-0001-9985-0387", "researcher": {"href": "https://publications.scilifelab.se/researcher/197cf8ba83ba430f9712b2f4d94dc3e5.json"}}, {"family": "W\u00e4hlby", "given": "Carolina", "initials": "C", "orcid": "0000-0002-4139-7003", "researcher": {"href": "https://publications.scilifelab.se/researcher/c50194fbc8524d95b7152663ccf17f29.json"}}], "type": "journal article", "published": "2020-10-19", "journal": {"title": "BMC Biol.", "issn": "1741-7007", "issn-l": "1741-7007", "volume": "18", "issue": "1", "pages": "144"}, "abstract": "Neuroanatomical compartments of the mouse brain are identified and outlined mainly based on manual annotations of samples using features related to tissue and cellular morphology, taking advantage of publicly available reference atlases. However, this task is challenging since sliced tissue sections are rarely perfectly parallel or angled with respect to sections in the reference atlas and organs from different individuals may vary in size and shape and requires manual annotation. With the advent of in situ sequencing technologies and automated approaches, it is now possible to profile the gene expression of targeted genes inside preserved tissue samples and thus spatially map biological processes across anatomical compartments.\r\n\r\nHere, we show how in situ sequencing data combined with dimensionality reduction and clustering can be used to identify spatial compartments that correspond to known anatomical compartments of the brain. We also visualize gradients in gene expression and sharp as well as smooth transitions between different compartments. We apply our method on mouse brain sections and show that a fully unsupervised approach can computationally define anatomical compartments, which are highly reproducible across individuals, using as few as 18 gene markers. We also show that morphological variation does not always follow gene expression, and different spatial compartments can be defined by various cell types with common morphological features but distinct gene expression profiles.\r\n\r\nWe show that spatial gene expression data can be used for unsupervised and unbiased annotations of mouse brain spatial compartments based only on molecular markers, without the need of subjective manual annotations based on tissue and cell morphology or matching reference atlases.", "doi": "10.1186/s12915-020-00874-5", "pmid": "33076915", "labels": {"BioImage Informatics": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1186/s12915-020-00874-5"}, {"db": "pmc", "key": "PMC7574211"}], "notes": [], "created": "2020-11-30T10:24:03.397Z", "modified": "2024-01-16T13:48:41.550Z"}, {"entity": "publication", "iuid": "3b8d1f21730c444f9488bdde02b7966a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3b8d1f21730c444f9488bdde02b7966a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3b8d1f21730c444f9488bdde02b7966a"}}, "title": "A high-stringency blueprint of the human proteome.", "authors": [{"family": "Adhikari", "given": "Subash", "initials": "S"}, {"family": "Nice", "given": "Edouard C", "initials": "EC"}, {"family": "Deutsch", "given": "Eric W", "initials": "EW"}, {"family": "Lane", "given": "Lydie", "initials": "L", "orcid": "0000-0002-9818-3030", "researcher": {"href": "https://publications.scilifelab.se/researcher/c0992244993b4f0799f58c63f39a5c5e.json"}}, {"family": "Omenn", "given": "Gilbert S", "initials": "GS", "orcid": "0000-0002-8976-6074", "researcher": {"href": "https://publications.scilifelab.se/researcher/c434ae7226ff49e8b00a33c37a46dd60.json"}}, {"family": "Pennington", "given": "Stephen R", "initials": "SR"}, {"family": "Paik", "given": "Young-Ki", "initials": "YK"}, {"family": "Overall", "given": "Christopher M", "initials": "CM", "orcid": "0000-0001-5844-2731", "researcher": {"href": "https://publications.scilifelab.se/researcher/1f770b082f2447fd96e1daab1b1bc4f1.json"}}, {"family": "Corrales", "given": "Fernando J", "initials": "FJ"}, {"family": "Cristea", "given": "Ileana M", "initials": "IM"}, {"family": "Van Eyk", "given": "Jennifer E", "initials": "JE", "orcid": "0000-0001-9050-148X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9e860403a0224d588958a9c588688ff6.json"}}, {"family": "Uhl\u00e9n", "given": "Mathias", "initials": "M", "orcid": "0000-0002-4858-8056", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff81da3cb0cf4262873b993a1b06798c.json"}}, {"family": "Lindskog", "given": "Cecilia", "initials": "C", "orcid": "0000-0001-5611-1015", "researcher": {"href": "https://publications.scilifelab.se/researcher/36b6a0f049274929b64dcb5061ca0588.json"}}, {"family": "Chan", "given": "Daniel W", "initials": "DW"}, {"family": "Bairoch", "given": "Amos", "initials": "A"}, {"family": "Waddington", "given": "James C", "initials": "JC"}, {"family": "Justice", "given": "Joshua L", "initials": "JL"}, {"family": "LaBaer", "given": "Joshua", "initials": "J"}, {"family": "Rodriguez", "given": "Henry", "initials": "H"}, {"family": "He", "given": "Fuchu", "initials": "F"}, {"family": "Kostrzewa", "given": "Markus", "initials": "M"}, {"family": "Ping", "given": "Peipei", "initials": "P"}, {"family": "Gundry", "given": "Rebekah L", "initials": "RL", "orcid": "0000-0002-9263-833X", "researcher": {"href": "https://publications.scilifelab.se/researcher/60163f86086644e9a74a7793d886dd3e.json"}}, {"family": "Stewart", "given": "Peter", "initials": "P"}, {"family": "Srivastava", "given": "Sanjeeva", "initials": "S"}, {"family": "Srivastava", "given": "Sudhir", "initials": "S"}, {"family": "Nogueira", "given": "Fabio C S", "initials": "FCS"}, {"family": "Domont", "given": "Gilberto B", "initials": "GB"}, {"family": "Vandenbrouck", "given": "Yves", "initials": "Y", "orcid": "0000-0002-1292-373X", "researcher": {"href": "https://publications.scilifelab.se/researcher/16eb301087cd46c5b12bdb276fdf561b.json"}}, {"family": "Lam", "given": "Maggie P Y", "initials": "MPY"}, {"family": "Wennersten", "given": "Sara", "initials": "S"}, {"family": "Vizcaino", "given": "Juan Antonio", "initials": "JA", "orcid": "0000-0002-3905-4335", "researcher": {"href": "https://publications.scilifelab.se/researcher/9df36c9559504428a42edba7ba33ec08.json"}}, {"family": "Wilkins", "given": "Marc", "initials": "M", "orcid": "0000-0002-5700-5684", "researcher": {"href": "https://publications.scilifelab.se/researcher/98c5bc0757d145d692312da866ebf51a.json"}}, {"family": "Schwenk", "given": "Jochen M", "initials": "JM", "orcid": "0000-0001-8141-8449", "researcher": {"href": "https://publications.scilifelab.se/researcher/aba5822711b246b397fffacb7ae403b3.json"}}, {"family": "Lundberg", "given": "Emma", "initials": "E", "orcid": "0000-0001-7034-0850", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ffe6259ceb540f385861b5ae52b3055.json"}}, {"family": "Bandeira", "given": "Nuno", "initials": "N", "orcid": "0000-0001-8385-3655", "researcher": {"href": "https://publications.scilifelab.se/researcher/d6377e04591748fc9450eaff4d41acff.json"}}, {"family": "Marko-Varga", "given": "Gyorgy", "initials": "G"}, {"family": "Weintraub", "given": "Susan T", "initials": "ST"}, {"family": "Pineau", "given": "Charles", "initials": "C"}, {"family": "Kusebauch", "given": "Ulrike", "initials": "U", "orcid": "0000-0001-6162-7577", "researcher": {"href": "https://publications.scilifelab.se/researcher/a0b4bcdb047c4b1fa84e513ea0eddd5e.json"}}, {"family": "Moritz", "given": "Robert L", "initials": "RL", "orcid": "0000-0002-3216-9447", "researcher": {"href": "https://publications.scilifelab.se/researcher/2aaa7d54f7de41cf915b47e8037c15cf.json"}}, {"family": "Ahn", "given": "Seong Beom", "initials": "SB"}, {"family": "Palmblad", "given": "Magnus", "initials": "M"}, {"family": "Snyder", "given": "Michael P", "initials": "MP", "orcid": "0000-0003-0784-7987", "researcher": {"href": "https://publications.scilifelab.se/researcher/a2594af48f3d45e68983030873c06cf5.json"}}, {"family": "Aebersold", "given": "Ruedi", "initials": "R", "orcid": "0000-0002-9576-3267", "researcher": {"href": "https://publications.scilifelab.se/researcher/9222eeba13464c618695f91ea8764abb.json"}}, {"family": "Baker", "given": "Mark S", "initials": "MS", "orcid": "0000-0001-5858-4035", "researcher": {"href": "https://publications.scilifelab.se/researcher/c4620f71cdce4e6e91264f96b74c6d84.json"}}], "type": "journal article", "published": "2020-10-16", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "11", "issue": "1", "pages": "5301", "issn-l": "2041-1723"}, "abstract": "The Human Proteome Organization (HUPO) launched the Human Proteome Project (HPP) in 2010, creating an international framework for global collaboration, data sharing, quality assurance and enhancing accurate annotation of the genome-encoded proteome. During the subsequent decade, the HPP established collaborations, developed guidelines and metrics, and undertook reanalysis of previously deposited community data, continuously increasing the coverage of the human proteome. On the occasion of the HPP's tenth anniversary, we here report a 90.4% complete high-stringency human proteome blueprint. This knowledge is essential for discerning molecular processes in health and disease, as we demonstrate by highlighting potential roles the human proteome plays in our understanding, diagnosis and treatment of cancers, cardiovascular and infectious diseases.", "doi": "10.1038/s41467-020-19045-9", "pmid": "33067450", "labels": {"Affinity Proteomics Stockholm": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-19045-9"}, {"db": "pmc", "key": "PMC7568584"}], "notes": [], "created": "2020-12-10T19:07:09.284Z", "modified": "2021-11-10T12:46:20.338Z"}, {"entity": "publication", "iuid": "3c85b2fe425e40f7816b5c4810c0231e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3c85b2fe425e40f7816b5c4810c0231e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3c85b2fe425e40f7816b5c4810c0231e"}}, "title": "Fulvestrant-Mediated Attenuation of the Innate Immune Response Decreases ER+ Breast Cancer Growth In Vivo More Effectively than Tamoxifen.", "authors": [{"family": "Abrahamsson", "given": "Annelie", "initials": "A", "orcid": "0000-0002-6791-7951", "researcher": {"href": "https://publications.scilifelab.se/researcher/b3a5b588a24b495fabdc337c10f69f59.json"}}, {"family": "Rodriguez", "given": "Gabriela Vazquez", "initials": "GV", "orcid": "0000-0001-9310-2433", "researcher": {"href": "https://publications.scilifelab.se/researcher/3af0ed418b6e4b0ab26565a4b1e7a033.json"}}, {"family": "Dabrosin", "given": "Charlotta", "initials": "C", "orcid": "0000-0001-7191-0018", "researcher": {"href": "https://publications.scilifelab.se/researcher/66c887621cb84be4a4bc1c4cfb4c86de.json"}}], "type": "journal article", "published": "2020-10-15", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "volume": "80", "issue": "20", "pages": "4487-4499", "issn-l": "0008-5472"}, "abstract": "Although blocking estrogen-dependent signaling is a cornerstone of adjuvant treatment for breast cancer, 25% of patients experience recurrent disease. Stroma events including innate immune responses are key in cancer progression. How different estrogen receptor (ER)-targeting therapies, including the partial agonist tamoxifen and the pure antagonist fulvestrant, affect the tumor stroma has not yet been elucidated. Fulvestrant is used in only postmenopausal patients, and its effects in the presence of estradiol remain undetermined. Here we observe that fulvestrant decreases ER+ breast cancer growth compared with tamoxifen in the presence of physiologic levels of estradiol in human breast cancer in nude mice and in murine breast cancer in immune-competent mice. Fulvestrant significantly inhibited macrophage and neutrophil infiltration in both models. These effects were corroborated in a zebrafish model where fulvestrant inhibited neutrophil- and macrophage-dependent cancer cell dissemination more effectively than tamoxifen. A comprehensive analysis of 234 human proteins released into the cancer microenvironment by the cancer cells sampled via microdialysis in vivo revealed that 38 proteins were altered following both treatments; 25 of these proteins were associated with immune response and were altered by fulvestrant only. Compared with tamoxifen, fulvestrant significantly affected inflammatory proteins released by murine stroma cells. Importantly, in vivo microdialysis of human ER+ breast cancer revealed that the majority of affected proteins in murine models were upregulated in patients. Together, these results suggest that fulvestrant targets ER+ breast cancer more effectively than tamoxifen even in the presence of estradiol, mainly by attenuation of the innate immune response. SIGNIFICANCE: These findings demonstrate novel effects of the pure antiestrogen fulvestrant in ER+ breast cancer and evaluate its effects under physiologic levels of estradiol, representative of premenopausal patients.", "doi": "10.1158/0008-5472.CAN-20-1705", "pmid": "32855207", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pii", "key": "0008-5472.CAN-20-1705"}], "notes": [], "created": "2020-09-15T07:21:32.922Z", "modified": "2021-11-10T12:47:55.756Z"}, {"entity": "publication", "iuid": "f870d06d8746421ebbb308e2a749cf8e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f870d06d8746421ebbb308e2a749cf8e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f870d06d8746421ebbb308e2a749cf8e"}}, "title": "Engineering Af1521 improves ADP-ribose binding and identification of ADP-ribosylated proteins.", "authors": [{"family": "Nowak", "given": "Kathrin", "initials": "K"}, {"family": "Rosenthal", "given": "Florian", "initials": "F"}, {"family": "Karlberg", "given": "Tobias", "initials": "T"}, {"family": "B\u00fctepage", "given": "Mareike", "initials": "M"}, {"family": "Thorsell", "given": "Ann-Gerd", "initials": "AG"}, {"family": "Dreier", "given": "Birgit", "initials": "B"}, {"family": "Grossmann", "given": "Jonas", "initials": "J"}, {"family": "Sobek", "given": "Jens", "initials": "J"}, {"family": "Imhof", "given": "Ralph", "initials": "R"}, {"family": "L\u00fcscher", "given": "Bernhard", "initials": "B", "orcid": "0000-0002-9622-8709", "researcher": {"href": "https://publications.scilifelab.se/researcher/b777138c7e7740c5926a5385997dec9c.json"}}, {"family": "Sch\u00fcler", "given": "Herwig", "initials": "H", "orcid": "0000-0003-4059-3501", "researcher": {"href": "https://publications.scilifelab.se/researcher/f49b25ddfc934f3ca41020c3f38c6bfc.json"}}, {"family": "Pl\u00fcckthun", "given": "Andreas", "initials": "A", "orcid": "0000-0003-4191-5306", "researcher": {"href": "https://publications.scilifelab.se/researcher/3f67a65bf469443a89665bd244bfd0f7.json"}}, {"family": "Leslie Pedrioli", "given": "Deena M", "initials": "DM", "orcid": "0000-0003-2342-8010", "researcher": {"href": "https://publications.scilifelab.se/researcher/6d2182b2344f4758abdf6fb8a05a39eb.json"}}, {"family": "Hottiger", "given": "Michael O", "initials": "MO", "orcid": "0000-0002-7323-2270", "researcher": {"href": "https://publications.scilifelab.se/researcher/8cc0bd6ccac3417fb8c04e02a5833efd.json"}}], "type": "journal article", "published": "2020-10-15", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "11", "issue": "1", "pages": "5199", "issn-l": "2041-1723"}, "abstract": "Protein ADP-ribosylation is a reversible post-translational modification that regulates important cellular functions. The identification of modified proteins has proven challenging and has mainly been achieved via enrichment methodologies. Random mutagenesis was used here to develop an engineered Af1521 ADP-ribose binding macro domain protein with 1000-fold increased affinity towards ADP-ribose. The crystal structure reveals that two point mutations K35E and Y145R form a salt bridge within the ADP-ribose binding domain. This forces the proximal ribose to rotate within the binding pocket and, as a consequence, improves engineered Af1521 ADPr-binding affinity. Its use in our proteomic ADP-ribosylome workflow increases the ADP-ribosylated protein identification rates and yields greater ADP-ribosylome coverage. Furthermore, generation of an engineered Af1521 Fc fusion protein confirms the improved detection of cellular ADP-ribosylation by immunoblot and immunofluorescence. Thus, this engineered isoform of Af1521 can also serve as a valuable tool for the analysis of cellular ADP-ribosylation under in vivo conditions.", "doi": "10.1038/s41467-020-18981-w", "pmid": "33060572", "labels": {"Protein Science Facility (PSF)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7566600"}, {"db": "pii", "key": "10.1038/s41467-020-18981-w"}], "notes": [], "created": "2024-04-03T14:24:02.267Z", "modified": "2024-04-03T14:24:02.738Z"}, {"entity": "publication", "iuid": "e202d7f45983406db8e9f04f3f572696", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e202d7f45983406db8e9f04f3f572696.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e202d7f45983406db8e9f04f3f572696"}}, "title": "Discovery of USP7 small-molecule allosteric inhibitors.", "authors": [{"family": "Engstr\u00f6m", "given": "Olof", "initials": "O"}, {"family": "Belda", "given": "Oscar", "initials": "O"}, {"family": "Kullman-Magnusson", "given": "Mari", "initials": "M"}, {"family": "Rapp", "given": "Mikaela", "initials": "M"}, {"family": "B\u00f6hm", "given": "Kerstin", "initials": "K"}, {"family": "Paul", "given": "Ralf", "initials": "R"}, {"family": "Henderson", "given": "Ian", "initials": "I"}, {"family": "Derbyshire", "given": "Dean", "initials": "D"}, {"family": "Karlstr\u00f6m", "given": "Sofia", "initials": "S"}, {"family": "Parkes", "given": "Kevin E B", "initials": "KEB"}, {"family": "Zhao", "given": "Hongtao", "initials": "H", "orcid": "0000-0002-9318-1052", "researcher": {"href": "https://publications.scilifelab.se/researcher/84eabf78ece645598d2317049bfa38a4.json"}}], "type": "journal article", "published": "2020-10-15", "journal": {"title": "Bioorg. Med. Chem. Lett.", "issn": "1464-3405", "volume": "30", "issue": "20", "pages": "127471", "issn-l": "0960-894X"}, "abstract": "Ubiquitin specific protease-7 (USP7) is considered an attractive target for cancer therapy by promoting degradation of the tumor suppressor p53 and negatively affecting the immune response to tumors. However, the development of selective non-covalent USP7 inhibitors has proven challenging. In this work we report the NMR characterization of a weak binder from SPR screening of an in-house fragment library which reveals that it binds to the allosteric palm site of the catalytic domain. Molecular modeling combined with 1HNMR saturation transfer difference and NOESY experiments enabled structure-based design of additional compounds showing IC50 values in the low-micromolar range with good selectivity over the closest homolog USP47. The most potent analogue represents a promising starting point for the development of novel, selective USP7 inhibitors.", "doi": "10.1016/j.bmcl.2020.127471", "pmid": "32781219", "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [{"db": "pii", "key": "S0960-894X(20)30582-5"}], "notes": [], "created": "2020-12-11T09:13:08.944Z", "modified": "2025-10-17T13:03:56.617Z"}, {"entity": "publication", "iuid": "0abd0bd865b04efcac3554e8f65e07c5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0abd0bd865b04efcac3554e8f65e07c5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0abd0bd865b04efcac3554e8f65e07c5"}}, "title": "The Structure of Riparian Vegetation in Agricultural Landscapes Influences Spider Communities and Aquatic-Terrestrial Linkages", "authors": [{"family": "Ramberg", "given": "Ellinor", "initials": "E"}, {"family": "Burdon", "given": "Francis J", "initials": "FJ", "orcid": "0000-0002-5398-4993", "researcher": {"href": "https://publications.scilifelab.se/researcher/853e9aa4ce714858a8ea19175bf20b35.json"}}, {"family": "Sargac", "given": "Jasmina", "initials": "J"}, {"family": "Kupilas", "given": "Benjamin", "initials": "B", "orcid": "0000-0002-4211-1679", "researcher": {"href": "https://publications.scilifelab.se/researcher/d0446ef756c84d138dbcdfdc94e9d85e.json"}}, {"family": "R\u00ee\u015fnoveanu", "given": "Geta", "initials": "G", "orcid": "0000-0002-5194-5448", "researcher": {"href": "https://publications.scilifelab.se/researcher/166324e3c75746de97c931838c3eba0f.json"}}, {"family": "Lau", "given": "Danny C P", "initials": "DCP", "orcid": "0000-0002-3246-7508", "researcher": {"href": "https://publications.scilifelab.se/researcher/28aa8ed05fc64662b9a72cf4bde0e59b.json"}}, {"family": "Johnson", "given": "Richard K", "initials": "RK"}, {"family": "McKie", "given": "Brendan G", "initials": "BG", "orcid": "0000-0002-1796-9497", "researcher": {"href": "https://publications.scilifelab.se/researcher/c30b998fd8384632ba0216c4ecfabc3d.json"}}], "type": "journal-article", "published": "2020-10-14", "journal": {"title": "Water", "issn": "2073-4441", "volume": "12", "issue": "10", "pages": "2855", "issn-l": null}, "abstract": null, "doi": "10.3390/w12102855", "pmid": null, "labels": {"Swedish Metabolomics Centre": "Service"}, "xrefs": [], "notes": [], "created": "2020-12-11T12:04:54.111Z", "modified": "2025-10-17T13:03:16.611Z"}, {"entity": "publication", "iuid": "c66db214519348c0863eeb3e089bbccc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c66db214519348c0863eeb3e089bbccc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c66db214519348c0863eeb3e089bbccc"}}, "title": "Analysis of translating mitoribosome reveals functional characteristics of translation in mitochondria of fungi.", "authors": [{"family": "Itoh", "given": "Yuzuru", "initials": "Y", "orcid": "0000-0001-7802-5572", "researcher": {"href": "https://publications.scilifelab.se/researcher/12516bf2aeb44f9ba7e380b7be1bf582.json"}}, {"family": "Naschberger", "given": "Andreas", "initials": "A"}, {"family": "Mortezaei", "given": "Narges", "initials": "N"}, {"family": "Herrmann", "given": "Johannes M", "initials": "JM", "orcid": "0000-0003-2081-4506", "researcher": {"href": "https://publications.scilifelab.se/researcher/8d45f53a0781428291e45ebb9ac8a372.json"}}, {"family": "Amunts", "given": "Alexey", "initials": "A", "orcid": "0000-0002-5302-1740", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7d0bf36ad1a47f5b5b88f78d1e15395.json"}}], "type": "journal article", "published": "2020-10-14", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "11", "issue": "1", "pages": "5187", "issn-l": "2041-1723"}, "abstract": "Mitoribosomes are specialized protein synthesis machineries in mitochondria. However, how mRNA binds to its dedicated channel, and tRNA moves as the mitoribosomal subunit rotate with respect to each other is not understood. We report models of the translating fungal mitoribosome with mRNA, tRNA and nascent polypeptide, as well as an assembly intermediate. Nicotinamide adenine dinucleotide (NAD) is found in the central protuberance of the large subunit, and the ATPase inhibitory factor 1 (IF1) in the small subunit. The models of the active mitoribosome explain how mRNA binds through a dedicated protein platform on the small subunit, tRNA is translocated with the help of the protein mL108, bridging it with L1 stalk on the large subunit, and nascent polypeptide paths through a newly shaped exit tunnel involving a series of structural rearrangements. An assembly intermediate is modeled with the maturation factor Atp25, providing insight into the biogenesis of the mitoribosomal large subunit and translation regulation.", "doi": "10.1038/s41467-020-18830-w", "pmid": "33056988", "labels": {"Cryo-EM": "Service", "Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-18830-w"}, {"db": "pmc", "key": "PMC7560712"}], "notes": [], "created": "2020-10-14T14:19:09.292Z", "modified": "2021-11-10T12:44:48.768Z"}, {"entity": "publication", "iuid": "25837b6d08ab4c55b52b7bcc80655783", "links": {"self": {"href": "https://publications.scilifelab.se/publication/25837b6d08ab4c55b52b7bcc80655783.json"}, "display": {"href": "https://publications.scilifelab.se/publication/25837b6d08ab4c55b52b7bcc80655783"}}, "title": "Novel pathogenic genomic variants leading to autosomal dominant and recessive Robinow syndrome.", "authors": [{"family": "Zhang", "given": "Chaofan", "initials": "C", "orcid": "0000-0003-0504-5999", "researcher": {"href": "https://publications.scilifelab.se/researcher/76aee864d3c0444d8c7eabe94b0df996.json"}}, {"family": "Mazzeu", "given": "Juliana F", "initials": "JF", "orcid": "0000-0002-6161-0510", "researcher": {"href": "https://publications.scilifelab.se/researcher/08c358e857ad458298fbd0cbb7621a2b.json"}}, {"family": "Eisfeldt", "given": "Jesper", "initials": "J"}, {"family": "Grochowski", "given": "Christopher M", "initials": "CM", "orcid": "0000-0002-3884-7720", "researcher": {"href": "https://publications.scilifelab.se/researcher/c94bd6d4a43e41f2990ae8b9426c0312.json"}}, {"family": "White", "given": "Janson", "initials": "J"}, {"family": "Akdemir", "given": "Zeynep C", "initials": "ZC"}, {"family": "Jhangiani", "given": "Shalini N", "initials": "SN"}, {"family": "Muzny", "given": "Donna M", "initials": "DM"}, {"family": "Gibbs", "given": "Richard A", "initials": "RA", "orcid": "0000-0002-1356-5698", "researcher": {"href": "https://publications.scilifelab.se/researcher/b82176147e434163a72c946839708743.json"}}, {"family": "Lindstrand", "given": "Anna", "initials": "A"}, {"family": "Lupski", "given": "James R", "initials": "JR", "orcid": "0000-0001-9907-9246", "researcher": {"href": "https://publications.scilifelab.se/researcher/88dd1dee9767489aaf25865670feb7b7.json"}}, {"family": "Sutton", "given": "V Reid", "initials": "VR"}, {"family": "Carvalho", "given": "Claudia M B", "initials": "CMB", "orcid": "0000-0002-2090-298X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3a1a6b6936aa442384c5aef0eff0715a.json"}}], "type": "journal article", "published": "2020-10-13", "journal": {"title": "Am. J. Med. Genet. A", "issn": "1552-4833", "volume": null, "issue": null, "issn-l": "1552-4825"}, "abstract": "Robinow syndrome (RS) is a genetically heterogeneous disorder characterized by skeletal dysplasia and a distinctive facial appearance. Previous studies have revealed locus heterogeneity with rare variants in DVL1, DVL3, FZD2, NXN, ROR2, and WNT5A underlying the etiology of RS. The aforementioned \"Robinow-associated genes\" and their gene products all play a role in the WNT/planar cell polarity signaling pathway. We performed gene-targeted Sanger sequencing, exome sequencing, genome sequencing, and array comparative genomic hybridization on four subjects with a clinical diagnosis of RS who had not had prior DNA testing. Individuals in our cohort were found to carry pathogenic or likely pathogenic variants in three RS related genes: DVL1, ROR2, and NXN. One subject was found to have a nonsense variant (c.817C > T [p.Gln273*]) in NXN in trans with an ~1 Mb telomeric deletion on chromosome 17p containing NXN, which supports our contention that biallelic NXN variant alleles are responsible for a novel autosomal recessive RS locus. These findings provide increased understanding of the role of WNT signaling in skeletal development and maintenance. These data further support the hypothesis that dysregulation of the noncanonical WNT pathway in humans gives rise to RS.", "doi": "10.1002/ajmg.a.61908", "pmid": "33048444", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8445516"}, {"db": "mid", "key": "NIHMS1735294"}], "notes": [], "created": "2020-12-07T16:32:22.731Z", "modified": "2021-11-10T12:46:23.684Z"}, {"entity": "publication", "iuid": "b24db4ffd64042678ddedf6969ba98f9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b24db4ffd64042678ddedf6969ba98f9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b24db4ffd64042678ddedf6969ba98f9"}}, "title": "The influence of common polygenic risk and gene sets on social skills group training response in autism spectrum disorder.", "authors": [{"family": "Li", "given": "Danyang", "initials": "D"}, {"family": "Choque-Olsson", "given": "Nora", "initials": "N"}, {"family": "Jiao", "given": "Hong", "initials": "H"}, {"family": "Norgren", "given": "Nina", "initials": "N"}, {"family": "Jonsson", "given": "Ulf", "initials": "U"}, {"family": "B\u00f6lte", "given": "Sven", "initials": "S"}, {"family": "Tammimies", "given": "Kristiina", "initials": "K", "orcid": "0000-0002-8324-4697", "researcher": {"href": "https://publications.scilifelab.se/researcher/ba19ec07147743c6942ea10c9a92482a.json"}}], "type": "journal article", "published": "2020-10-12", "journal": {"title": "npj Genom. Med.", "issn": "2056-7944", "volume": "5", "issue": "1", "pages": "45", "issn-l": "2056-7944"}, "abstract": "Social skills group training (SSGT) is a frequently used behavioral intervention in autism spectrum disorder (ASD), but the effects are moderate and heterogeneous. Here, we analyzed the effect of polygenic risk score (PRS) and common variants in gene sets on the intervention outcome. Participants from the largest randomized clinical trial of SSGT in ASD to date were selected (N = 188, 99 from SSGT, 89 from standard care) to calculate association between the outcomes in the SSGT trial and PRSs for ASD, attention-deficit hyperactivity disorder (ADHD), and educational attainment. In addition, specific gene sets were selected to evaluate their role on intervention outcomes. Among all participants in the trial, higher PRS for ADHD was associated with significant improvement in the outcome measure, the parental-rated Social Responsiveness Scale. The significant association was due to better outcomes in the standard care group for individuals with higher PRS for ADHD (post-intervention: \u03b2 = -4.747, P = 0.0129; follow-up: \u03b2 = -5.309, P = 0.0083). However, when contrasting the SSGT and standard care group, an inferior outcome in the SSGT group was associated with higher ADHD PRS at follow-up (\u03b2 = 6.67, P = 0.016). Five gene sets within the synaptic category showed a nominal association with reduced response to interventions. We provide preliminary evidence that genetic liability calculated from common variants could influence the intervention outcomes. In the future, larger cohorts should be used to investigate how genetic contribution affects individual response to ASD interventions.", "doi": "10.1038/s41525-020-00152-x", "pmid": "33083014", "labels": {"Bioinformatics Long-term Support WABI": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "152"}, {"db": "pmc", "key": "PMC7550579"}], "notes": [], "created": "2020-11-04T07:41:31.187Z", "modified": "2024-01-16T13:48:41.558Z"}, {"entity": "publication", "iuid": "1f47acaed3054c5cb53f17d2bf96f5b0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1f47acaed3054c5cb53f17d2bf96f5b0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1f47acaed3054c5cb53f17d2bf96f5b0"}}, "title": "TIF-Seq2 disentangles overlapping isoforms in complex human transcriptomes.", "authors": [{"family": "Wang", "given": "Jingwen", "initials": "J"}, {"family": "Li", "given": "Bingnan", "initials": "B"}, {"family": "Marques", "given": "Sueli", "initials": "S"}, {"family": "Steinmetz", "given": "Lars M", "initials": "LM"}, {"family": "Wei", "given": "Wu", "initials": "W"}, {"family": "Pelechano", "given": "Vicent", "initials": "V"}], "type": "journal article", "published": "2020-10-09", "journal": {"title": "Nucleic Acids Res.", "issn": "1362-4962", "volume": "48", "issue": "18", "pages": "e104", "issn-l": "0305-1048"}, "abstract": "Eukaryotic transcriptomes are complex, involving thousands of overlapping transcripts. The interleaved nature of the transcriptomes limits our ability to identify regulatory regions, and in some cases can lead to misinterpretation of gene expression. To improve the understanding of the overlapping transcriptomes, we have developed an optimized method, TIF-Seq2, able to sequence simultaneously the 5' and 3' ends of individual RNA molecules at single-nucleotide resolution. We investigated the transcriptome of a well characterized human cell line (K562) and identified thousands of unannotated transcript isoforms. By focusing on transcripts which are challenging to be investigated with RNA-Seq, we accurately defined boundaries of lowly expressed unannotated and read-through transcripts putatively encoding fusion genes. We validated our results by targeted long-read sequencing and standard RNA-Seq for chronic myeloid leukaemia patient samples. Taking the advantage of TIF-Seq2, we explored transcription regulation among overlapping units and investigated their crosstalk. We show that most overlapping upstream transcripts use poly(A) sites within the first 2 kb of the downstream transcription units. Our work shows that, by paring the 5' and 3' end of each RNA, TIF-Seq2 can improve the annotation of complex genomes, facilitate accurate assignment of promoters to genes and easily identify transcriptionally fused genes.", "doi": "10.1093/nar/gkaa691", "pmid": "32816037", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7544212"}, {"db": "pii", "key": "5894951"}], "notes": [], "created": "2023-11-27T21:53:34.866Z", "modified": "2024-01-16T13:48:41.565Z"}, {"entity": "publication", "iuid": "1ee4818dc4184bc6b75488e144483a8b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1ee4818dc4184bc6b75488e144483a8b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1ee4818dc4184bc6b75488e144483a8b"}}, "title": "Optotracing for selective fluorescence-based detection, visualization and quantification of live S. aureus in real-time.", "authors": [{"family": "Butina", "given": "Karen", "initials": "K"}, {"family": "Tomac", "given": "Ana", "initials": "A"}, {"family": "Choong", "given": "Ferdinand X", "initials": "FX"}, {"family": "Shirani", "given": "Hamid", "initials": "H"}, {"family": "Nilsson", "given": "K Peter R", "initials": "KPR"}, {"family": "L\u00f6ffler", "given": "Susanne", "initials": "S"}, {"family": "Richter-Dahlfors", "given": "Agneta", "initials": "A", "orcid": "0000-0002-5479-7591", "researcher": {"href": "https://publications.scilifelab.se/researcher/880ab0b32e5d4a38ae5500b7f693b67f.json"}}], "type": "journal article", "published": "2020-10-09", "journal": {"title": "NPJ Biofilms Microbiomes", "issn": "2055-5008", "volume": "6", "issue": "1", "pages": "35", "issn-l": "2055-5008"}, "abstract": "Methods for bacterial detection are needed to advance the infection research and diagnostics. Based on conformation-sensitive fluorescent tracer molecules, optotracing was recently established for dynamic detection and visualization of structural amyloids and polysaccharides in the biofilm matrix of gram-negative bacteria. Here, we extend the use of optotracing for detection of gram-positive bacteria, focussing on the clinically relevant opportunistic human pathogen Staphylococcus aureus. We identify a donor-acceptor-donor-type optotracer, whose binding-induced fluorescence enables real-time detection, quantification, and visualization of S. aureus in monoculture and when mixed with gram-negative Salmonella Enteritidis. An algorithm-based automated high-throughput screen of 1920 S. aureus transposon mutants recognized the cell envelope as the binding target, which was corroborated by super-resolution microscopy of bacterial cells and spectroscopic analysis of purified cell wall components. The binding event was essentially governed by hydrophobic interactions, which permitted custom-designed tuning of the binding selectivity towards S. aureus versus Enterococcus faecalis by appropriate selection of buffer conditions. Collectively this work demonstrates optotracing as an enabling technology relevant for any field of basic and applied research, where visualization and detection of S. aureus is needed.", "doi": "10.1038/s41522-020-00150-y", "pmid": "33037198", "labels": {"Integrated Microscopy Technologies Stockholm": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41522-020-00150-y"}, {"db": "pmc", "key": "PMC7547713"}], "notes": [], "created": "2020-10-20T15:13:26.665Z", "modified": "2021-11-10T12:46:27.471Z"}, {"entity": "publication", "iuid": "e173e02b94644b7b8a5040986accb4a0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e173e02b94644b7b8a5040986accb4a0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e173e02b94644b7b8a5040986accb4a0"}}, "title": "Generation and validation of recombinant antibodies to study human aminoacyl-tRNA synthetases.", "authors": [{"family": "Preger", "given": "Charlotta", "initials": "C"}, {"family": "Wigren", "given": "Edvard", "initials": "E", "orcid": "0000-0002-7933-0939", "researcher": {"href": "https://publications.scilifelab.se/researcher/c844b8d4d0554443b369f6c0f128ea7e.json"}}, {"family": "Ossipova", "given": "Elena", "initials": "E"}, {"family": "Marks", "given": "Carolyn", "initials": "C"}, {"family": "Lengqvist", "given": "Johan", "initials": "J"}, {"family": "Hofstr\u00f6m", "given": "Camilla", "initials": "C"}, {"family": "Andersson", "given": "Oskar", "initials": "O"}, {"family": "Jakobsson", "given": "Per-Johan", "initials": "PJ", "orcid": "0000-0001-7665-9715", "researcher": {"href": "https://publications.scilifelab.se/researcher/8fb148e2233b4541bc7c8b340f0cf12c.json"}}, {"family": "Gr\u00e4slund", "given": "Susanne", "initials": "S"}, {"family": "Persson", "given": "Helena", "initials": "H", "orcid": "0000-0002-2965-0395", "researcher": {"href": "https://publications.scilifelab.se/researcher/971d18bca1874c9cb8630c15c530c11d.json"}}], "type": "journal article", "published": "2020-10-09", "journal": {"title": "J. Biol. Chem.", "issn": "1083-351X", "issn-l": "0021-9258", "volume": "295", "issue": "41", "pages": "13981-13993"}, "abstract": "Aminoacyl-tRNA synthetases (aaRSs) have long been viewed as mere housekeeping proteins and have therefore often been overlooked in drug discovery. However, recent findings have revealed that many aaRSs have noncanonical functions, and several of the aaRSs have been linked to autoimmune diseases, cancer, and neurological disorders. Deciphering these roles has been challenging because of a lack of tools to enable their study. To help solve this problem, we have generated recombinant high-affinity antibodies for a collection of thirteen cytoplasmic and one mitochondrial aaRSs. Selected domains of these proteins were produced recombinantly in Escherichia coli and used as antigens in phage display selections using a synthetic human single-chain fragment variable library. All targets yielded large sets of antibody candidates that were validated through a panel of binding assays against the purified antigen. Furthermore, the top-performing binders were tested in immunoprecipitation followed by MS for their ability to capture the endogenous protein from mammalian cell lysates. For antibodies targeting individual members of the multi-tRNA synthetase complex, we were able to detect all members of the complex, co-immunoprecipitating with the target, in several cell types. The functionality of a subset of binders for each target was also confirmed using immunofluorescence. The sequences of these proteins have been deposited in publicly available databases and repositories. We anticipate that this open source resource, in the form of high-quality recombinant proteins and antibodies, will accelerate and empower future research of the role of aaRSs in health and disease.", "doi": "10.1074/jbc.RA120.012893", "pmid": "32817337", "labels": {"Autoimmunity and Serology Profiling": "Service", "Drug Discovery and Development": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0021-9258(17)49797-3"}, {"db": "pmc", "key": "PMC7549041"}], "notes": [], "created": "2020-12-02T15:16:20.268Z", "modified": "2025-10-17T13:05:07.951Z"}, {"entity": "publication", "iuid": "e980f00b87dd45d3ab9ceb6c3c4cca0c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e980f00b87dd45d3ab9ceb6c3c4cca0c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e980f00b87dd45d3ab9ceb6c3c4cca0c"}}, "title": "An embryonic stem cell-specific heterochromatin state promotes core histone exchange in the absence of DNA accessibility.", "authors": [{"family": "Navarro", "given": "Carmen", "initials": "C", "orcid": "0000-0001-5438-9654", "researcher": {"href": "https://publications.scilifelab.se/researcher/85a9184774364d2592961587bdce8c85.json"}}, {"family": "Lyu", "given": "Jing", "initials": "J", "orcid": "0000-0001-9529-6972", "researcher": {"href": "https://publications.scilifelab.se/researcher/cbe28157081c49debba23f0b9ebd9c74.json"}}, {"family": "Katsori", "given": "Anna-Maria", "initials": "AM", "orcid": "0000-0002-5975-2931", "researcher": {"href": "https://publications.scilifelab.se/researcher/1a338e7f888b4e7fa663fdd87d667713.json"}}, {"family": "Caridha", "given": "Rozina", "initials": "R"}, {"family": "Els\u00e4sser", "given": "Simon J", "initials": "SJ", "orcid": "0000-0001-8724-4849", "researcher": {"href": "https://publications.scilifelab.se/researcher/fcf26e35e037499aa1441a7738ba61af.json"}}], "type": "journal article", "published": "2020-10-09", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "11", "issue": "1", "pages": "5095", "issn-l": "2041-1723"}, "abstract": "Nucleosome turnover concomitant with incorporation of the replication-independent histone variant H3.3 is a hallmark of regulatory regions in the animal genome. Nucleosome turnover is known to be universally linked to DNA accessibility and histone acetylation. In mouse embryonic stem cells, H3.3 is also highly enriched at interstitial heterochromatin, most prominently at intracisternal A-particle endogenous retroviral elements. Interstitial heterochromatin is established over confined domains by the TRIM28-KAP1/SETDB1 corepressor complex and has stereotypical features of repressive chromatin, such as H3K9me3 and recruitment of all HP1 isoforms. Here, we demonstrate that fast histone turnover and H3.3 incorporation is compatible with these hallmarks of heterochromatin. Further, we find that Smarcad1 chromatin remodeler evicts nucleosomes generating accessible DNA. Free DNA is repackaged via DAXX-mediated nucleosome assembly with histone variant H3.3 in this dynamic heterochromatin state. Loss of H3.3 in mouse embryonic stem cells elicits a highly specific opening of interstitial heterochromatin with minimal effects on other silent or active regions of the genome.", "doi": "10.1038/s41467-020-18863-1", "pmid": "33037201", "labels": {"Protein Science Facility (PSF)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7547087"}, {"db": "pii", "key": "10.1038/s41467-020-18863-1"}], "notes": [], "created": "2024-04-03T14:21:34.373Z", "modified": "2024-04-03T14:22:37.597Z"}, {"entity": "publication", "iuid": "db71f369517e425cac0b1c66d3c937e0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/db71f369517e425cac0b1c66d3c937e0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/db71f369517e425cac0b1c66d3c937e0"}}, "title": "SARS-CoV-2 exposure, symptoms and seroprevalence in healthcare workers in Sweden.", "authors": [{"family": "Rudberg", "given": "Ann-Sofie", "initials": "AS", "orcid": "0000-0003-3616-9943", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e81215bbec8467388ec0592d4110169.json"}}, {"family": "Havervall", "given": "Sebastian", "initials": "S"}, {"family": "M\u00e5nberg", "given": "Anna", "initials": "A", "orcid": "0000-0002-0056-1313", "researcher": {"href": "https://publications.scilifelab.se/researcher/6d155273b5b54e61b773f263e4f2ce9b.json"}}, {"family": "Jernbom Falk", "given": "August", "initials": "A", "orcid": "0000-0002-7773-1851", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe6400bde68b46899515cef5bea05fca.json"}}, {"family": "Aguilera", "given": "Katherina", "initials": "K"}, {"family": "Ng", "given": "Henry", "initials": "H", "orcid": "0000-0003-2873-9088", "researcher": {"href": "https://publications.scilifelab.se/researcher/5fcb12c664a64724b5cd42a1267a5bea.json"}}, {"family": "Gabrielsson", "given": "Lena", "initials": "L"}, {"family": "Salomonsson", "given": "Ann-Christin", "initials": "AC"}, {"family": "Hanke", "given": "Leo", "initials": "L", "orcid": "0000-0001-5514-2418", "researcher": {"href": "https://publications.scilifelab.se/researcher/ece050a286f946f6807170cffc9320e7.json"}}, {"family": "Murrell", "given": "Ben", "initials": "B"}, {"family": "McInerney", "given": "Gerald", "initials": "G", "orcid": "0000-0003-2257-7241", "researcher": {"href": "https://publications.scilifelab.se/researcher/5ac2f68095fe4426b97ec070865e5091.json"}}, {"family": "Olofsson", "given": "Jennie", "initials": "J"}, {"family": "Andersson", "given": "Eni", "initials": "E", "orcid": "0000-0002-5115-0637", "researcher": {"href": "https://publications.scilifelab.se/researcher/ef94cf857c3746088cd01cee49242f24.json"}}, {"family": "Hellstr\u00f6m", "given": "Cecilia", "initials": "C", "orcid": "0000-0003-0880-5375", "researcher": {"href": "https://publications.scilifelab.se/researcher/dbf3f75938f0442a9b1ae5c98565f44a.json"}}, {"family": "Bayati", "given": "Shaghayegh", "initials": "S"}, {"family": "Bergstr\u00f6m", "given": "Sofia", "initials": "S"}, {"family": "Pin", "given": "Elisa", "initials": "E"}, {"family": "Sj\u00f6berg", "given": "Ronald", "initials": "R", "orcid": "0000-0003-1363-5796", "researcher": {"href": "https://publications.scilifelab.se/researcher/d08326da26da422ab445a26563843e79.json"}}, {"family": "Tegel", "given": "Hanna", "initials": "H"}, {"family": "Hedhammar", "given": "My", "initials": "M"}, {"family": "Phillipson", "given": "Mia", "initials": "M"}, {"family": "Nilsson", "given": "Peter", "initials": "P", "orcid": "0000-0002-4657-8532", "researcher": {"href": "https://publications.scilifelab.se/researcher/799bcf1cf8cf451296f4535dd4ca9dc0.json"}}, {"family": "Hober", "given": "Sophia", "initials": "S", "orcid": "0000-0003-0605-8417", "researcher": {"href": "https://publications.scilifelab.se/researcher/f8dd8ee4264d4e4b912dacad3106f40a.json"}}, {"family": "Th\u00e5lin", "given": "Charlotte", "initials": "C", "orcid": "0000-0002-1345-6491", "researcher": {"href": "https://publications.scilifelab.se/researcher/130fb6ef6b774613a767e98f9f9b2eb4.json"}}], "type": "journal article", "published": "2020-10-08", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "11", "issue": "1", "pages": "5064", "issn-l": "2041-1723"}, "abstract": "SARS-CoV-2 may pose an occupational health risk to healthcare workers. Here, we report the seroprevalence of SARS-CoV-2 antibodies, self-reported symptoms and occupational exposure to SARS-CoV-2 among healthcare workers at a large acute care hospital in Sweden. The seroprevalence of IgG antibodies against SARS-CoV-2 was 19.1% among the 2149 healthcare workers recruited between April 14th and May 8th 2020, which was higher than the reported regional seroprevalence during the same time period. Symptoms associated with seroprevalence were anosmia (odds ratio (OR) 28.4, 95% CI 20.6-39.5) and ageusia (OR 19.2, 95% CI 14.3-26.1). Seroprevalence was also associated with patient contact (OR 2.9, 95% CI 1.9-4.5) and covid-19 patient contact (OR 3.3, 95% CI 2.2-5.3). These findings imply an occupational risk for SARS-CoV-2 infection among healthcare workers. Continued measures are warranted to assure healthcare workers safety and reduce transmission from healthcare workers to patients and to the community.", "doi": "10.1038/s41467-020-18848-0", "pmid": "33033249", "labels": {"Autoimmunity and Serology Profiling": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-18848-0"}, {"db": "pmc", "key": "PMC7544689"}], "notes": [], "created": "2020-10-10T20:52:35.390Z", "modified": "2021-11-10T12:46:29.669Z"}, {"entity": "publication", "iuid": "c4770d32279c41e2b19898b2333d7374", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c4770d32279c41e2b19898b2333d7374.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c4770d32279c41e2b19898b2333d7374"}}, "title": "Temporal changes in the vaginal microbiota in self-samples and its association with persistent HPV16 infection and CIN2.", "authors": [{"family": "Berggrund", "given": "Malin", "initials": "M"}, {"family": "Gustavsson", "given": "Inger", "initials": "I"}, {"family": "Aarnio", "given": "Riina", "initials": "R"}, {"family": "Lindberg", "given": "Julia Hedlund", "initials": "JH"}, {"family": "Sanner", "given": "Karin", "initials": "K"}, {"family": "Wikstr\u00f6m", "given": "Ingrid", "initials": "I"}, {"family": "Enroth", "given": "Stefan", "initials": "S"}, {"family": "Bunikis", "given": "Ignas", "initials": "I"}, {"family": "Olovsson", "given": "Matts", "initials": "M"}, {"family": "Gyllensten", "given": "Ulf", "initials": "U", "orcid": "0000-0002-6316-3355", "researcher": {"href": "https://publications.scilifelab.se/researcher/e8739f0f42c44019ab88a49db350a4f2.json"}}], "type": "journal article", "published": "2020-10-07", "journal": {"title": "Virol J", "issn": "1743-422X", "volume": "17", "issue": "1", "pages": "147", "issn-l": "1743-422X"}, "abstract": "The vaginal microbiota has been reported to be associated with HPV infection and cervical cancer. This study was performed to compare the vaginal microbiota at two timepoints in women performing self-sampling and had a persistent or transient HPV16 infection. The women were tested for 12 high-risk HPV (hrHPV) types but only women with single type (HPV16) were included to reduce confounding variables.\n\nIn total 96 women were included in this study. Of these, 26 were single positive for HPV16 in the baseline test and HPV negative in the follow-up test and 38 were single positive for HPV16 in both tests and diagnosed with CIN2+ in histology. In addition, 32 women that were negative for all 12 HPV tested were included. The samples of vaginal fluid were analyzed with the Ion 16S\u2122 Metagenomics Kit and Ion 16S\u2122 metagenomics module within the Ion Reporter\u2122 software.\n\nK-means clustering resulted in two Lactobacillus-dominated groups, one with Lactobacillus sp. and the other specifically with Lactobacillus iners. The two remaining clusters were dominated by a mixed non-Lactobacillus microbiota. HPV negative women had lower prevalence (28%) of the non-Lactobacill dominant cluster in the baseline test, as compared to women with HPV16 infection (42%) (p value = 0.0173). Transition between clusters were more frequent in women with persistent HPV16 infection (34%) as compared in women who cleared the HPV16 infection (19%) (p value = 0.036).\n\nThe vaginal microbiota showed a higher rate of transitioning between bacterial profiles in women with persistent HPV16 infection as compared to women with transient infection. This indicate an instability in the microenvironment in women with persistent HPV infection and development of CIN2+.", "doi": "10.1186/s12985-020-01420-z", "pmid": "33028395", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12985-020-01420-z"}, {"db": "pmc", "key": "PMC7541248"}], "notes": [], "created": "2020-11-11T15:22:20.552Z", "modified": "2024-01-16T13:48:41.572Z"}, {"entity": "publication", "iuid": "d4fc956d9ba04d4e90ea6dae2139f961", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d4fc956d9ba04d4e90ea6dae2139f961.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d4fc956d9ba04d4e90ea6dae2139f961"}}, "title": "GeneSetCluster: a tool for summarizing and integrating gene-set analysis results.", "authors": [{"family": "Ewing", "given": "Ewoud", "initials": "E", "orcid": "0000-0001-8644-366X", "researcher": {"href": "https://publications.scilifelab.se/researcher/aea9350a4f864d8e8781ab111b4f9273.json"}}, {"family": "Planell-Picola", "given": "Nuria", "initials": "N"}, {"family": "Jagodic", "given": "Maja", "initials": "M"}, {"family": "Gomez-Cabrero", "given": "David", "initials": "D"}], "type": "journal article", "published": "2020-10-07", "journal": {"title": "BMC Bioinformatics", "issn": "1471-2105", "volume": "21", "issue": "1", "pages": "443", "issn-l": "1471-2105"}, "abstract": "Gene-set analysis tools, which make use of curated sets of molecules grouped based on their shared functions, aim to identify which gene-sets are over-represented in the set of features that have been associated with a given trait of interest. Such tools are frequently used in gene-centric approaches derived from RNA-sequencing or microarrays such as Ingenuity or GSEA, but they have also been adapted for interval-based analysis derived from DNA methylation or ChIP/ATAC-sequencing. Gene-set analysis tools return, as a result, a list of significant gene-sets. However, while these results are useful for the researcher in the identification of major biological insights, they may be complex to interpret because many gene-sets have largely overlapping gene contents. Additionally, in many cases the result of gene-set analysis consists of a large number of gene-sets making it complicated to identify the major biological insights.\n\nWe present GeneSetCluster, a novel approach which allows clustering of identified gene-sets, from one or multiple experiments and/or tools, based on shared genes. GeneSetCluster calculates a distance score based on overlapping gene content, which is then used to cluster them together and as a result, GeneSetCluster identifies groups of gene-sets with similar gene-set definitions (i.e. gene content). These groups of gene-sets can aid the researcher to focus on such groups for biological interpretations.\n\nGeneSetCluster is a novel approach for grouping together post gene-set analysis results based on overlapping gene content. GeneSetCluster is implemented as a package in R. The package and the vignette can be downloaded at https://github.com/TranslationalBioinformaticsUnit.", "doi": "10.1186/s12859-020-03784-z", "pmid": "33028195", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12859-020-03784-z"}, {"db": "pmc", "key": "PMC7542881"}], "notes": [], "created": "2020-12-07T16:28:58.011Z", "modified": "2024-01-16T13:48:41.580Z"}, {"entity": "publication", "iuid": "79b99a6601fc4ed1b69ef32e4b793129", "links": {"self": {"href": "https://publications.scilifelab.se/publication/79b99a6601fc4ed1b69ef32e4b793129.json"}, "display": {"href": "https://publications.scilifelab.se/publication/79b99a6601fc4ed1b69ef32e4b793129"}}, "title": "Transcriptional responses in developing lesions of European common ash (Fraxinus excelsior) reveal genes responding to infection by Hymenoscyphus fraxineus.", "authors": [{"family": "Sahraei", "given": "Shadi Eshghi", "initials": "SE"}, {"family": "Cleary", "given": "Michelle", "initials": "M"}, {"family": "Stenlid", "given": "Jan", "initials": "J"}, {"family": "Brandstr\u00f6m Durling", "given": "Mikael", "initials": "M"}, {"family": "Elfstrand", "given": "Malin", "initials": "M", "orcid": "0000-0002-0214-5284", "researcher": {"href": "https://publications.scilifelab.se/researcher/2957dac173f4495a9245f0d8a9750606.json"}}], "type": "journal article", "published": "2020-10-06", "journal": {"title": "BMC Plant Biol.", "issn": "1471-2229", "volume": "20", "issue": "1", "pages": "455", "issn-l": "1471-2229"}, "abstract": "With the expanding ash dieback epidemic that has spread across the European continent, an improved functional understanding of the disease development in afflicted hosts is needed. The study investigated whether differences in necrosis extension between common ash (Fraxinus excelsior) trees with different levels of susceptibility to the fungus Hymenoscyphus fraxineus are associated with, and can be explained by, the differences in gene expression patterns. We inoculated seemingly healthy branches of each of two resistant and susceptible ash genotypes with H. fraxineus grown in a common garden.\n\nTen months after the inoculation, the length of necrosis on the resistant genotypes were shorter than on the susceptible genotypes. RNA sequencing of bark samples collected at the border of necrotic lesions and from healthy tissues distal to the lesion revealed relatively limited differences in gene expression patterns between susceptible and resistant genotypes. At the necrosis front, only 138 transcripts were differentially expressed between the genotype categories while 1082 were differentially expressed in distal, non-symptomatic tissues. Among these differentially expressed genes, several genes in the mevalonate (MVA) and iridoid pathways were found to be co-regulated, possibly indicating increased fluxes through these pathways in response to H. fraxineus. Comparison of transcriptional responses of symptomatic and non-symptomatic ash in a controlled greenhouse experiment revealed a relatively small set of genes that were differentially and concordantly expressed in both studies. This gene-set included the rate-limiting enzyme in the MVA pathway and a number of transcription factors. Furthermore, several of the concordantly expressed candidate genes show significant similarity to genes encoding players in the abscisic acid- or Jasmonate-signalling pathways.\n\nA set of candidate genes, concordantly expressed between field and greenhouse experiments, was identified. The candidates are associated with hormone signalling and specialized metabolite biosynthesis pathways indicating the involvement of these pathways in the response of the host to infection by H. fraxineus.", "doi": "10.1186/s12870-020-02656-1", "pmid": "33023496", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12870-020-02656-1"}, {"db": "pmc", "key": "PMC7541206"}], "notes": [], "created": "2020-12-07T16:28:55.489Z", "modified": "2024-01-16T13:48:41.587Z"}, {"entity": "publication", "iuid": "fb4bbf803de54b088cfb068d05fc005b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/fb4bbf803de54b088cfb068d05fc005b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/fb4bbf803de54b088cfb068d05fc005b"}}, "title": "Key insights in the AIDA community policy on sharing of clinical imaging data for research in Sweden.", "authors": [{"family": "Hedlund", "given": "Joel", "initials": "J", "orcid": "0000-0001-6443-3604", "researcher": {"href": "https://publications.scilifelab.se/researcher/241552a1caee487298f4eef04daa3023.json"}}, {"family": "Eklund", "given": "Anders", "initials": "A", "orcid": "0000-0001-7061-7995", "researcher": {"href": "https://publications.scilifelab.se/researcher/1dd215e5257a41e4866e3cfb15dce4db.json"}}, {"family": "Lundstr\u00f6m", "given": "Claes", "initials": "C", "orcid": "0000-0002-9368-0177", "researcher": {"href": "https://publications.scilifelab.se/researcher/0dbd78a0aa02482c9587af4c9e6331a5.json"}}], "type": "journal article", "published": "2020-10-06", "journal": {"title": "Sci Data", "issn": "2052-4463", "issn-l": "2052-4463", "volume": "7", "issue": "1", "pages": "331"}, "abstract": "Development of world-class artificial intelligence (AI) for medical imaging requires access to massive amounts of training data from clinical sources, but effective data sharing is often hindered by uncertainty regarding data protection. We describe an initiative to reduce this uncertainty through a policy describing a national community consensus on sound data sharing practices.", "doi": "10.1038/s41597-020-00674-0", "pmid": "33024103", "labels": {"AIDA Data Hub": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7538928"}, {"db": "pii", "key": "10.1038/s41597-020-00674-0"}], "notes": [], "created": "2021-11-10T16:53:56.042Z", "modified": "2023-05-25T16:01:47.054Z"}, {"entity": "publication", "iuid": "d65d460e50e0405eaa0e81048974930c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d65d460e50e0405eaa0e81048974930c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d65d460e50e0405eaa0e81048974930c"}}, "title": "Pre-extinction Demographic Stability and Genomic Signatures of Adaptation in the Woolly Rhinoceros.", "authors": [{"family": "Lord", "given": "Edana", "initials": "E", "orcid": "0000-0002-4717-1988", "researcher": {"href": "https://publications.scilifelab.se/researcher/05d936191b3c4ff3acbe71db566da595.json"}}, {"family": "Dussex", "given": "Nicolas", "initials": "N", "orcid": "0000-0002-9179-8593", "researcher": {"href": "https://publications.scilifelab.se/researcher/a8ce91163131424a99f8815c2cb96953.json"}}, {"family": "Kierczak", "given": "Marcin", "initials": "M", "orcid": "0000-0003-2629-5655", "researcher": {"href": "https://publications.scilifelab.se/researcher/6c13f96fb81f4ae2bfff5e91ac45388e.json"}}, {"family": "D\u00edez-Del-Molino", "given": "David", "initials": "D"}, {"family": "Ryder", "given": "Oliver A", "initials": "OA"}, {"family": "Stanton", "given": "David W G", "initials": "DWG", "orcid": "0000-0002-9753-3166", "researcher": {"href": "https://publications.scilifelab.se/researcher/2732b89a34b54967bcb87811cdc3fb1c.json"}}, {"family": "Gilbert", "given": "M Thomas P", "initials": "MTP"}, {"family": "S\u00e1nchez-Barreiro", "given": "F\u00e1tima", "initials": "F"}, {"family": "Zhang", "given": "Guojie", "initials": "G"}, {"family": "Sinding", "given": "Mikkel-Holger S", "initials": "MS"}, {"family": "Lorenzen", "given": "Eline D", "initials": "ED"}, {"family": "Willerslev", "given": "Eske", "initials": "E", "orcid": "0000-0002-7081-6748", "researcher": {"href": "https://publications.scilifelab.se/researcher/da0055841300427e85d9af38b1863ef1.json"}}, {"family": "Protopopov", "given": "Albert", "initials": "A"}, {"family": "Shidlovskiy", "given": "Fedor", "initials": "F"}, {"family": "Fedorov", "given": "Sergey", "initials": "S"}, {"family": "Bocherens", "given": "Herv\u00e9", "initials": "H"}, {"family": "Nathan", "given": "Senthilvel K S S", "initials": "SKSS"}, {"family": "Goossens", "given": "Benoit", "initials": "B"}, {"family": "van der Plicht", "given": "Johannes", "initials": "J", "orcid": "0000-0003-4298-7037", "researcher": {"href": "https://publications.scilifelab.se/researcher/c115c95efd014b748c698a802f25f2d5.json"}}, {"family": "Chan", "given": "Yvonne L", "initials": "YL", "orcid": "0000-0002-8073-4025", "researcher": {"href": "https://publications.scilifelab.se/researcher/2fdb2d9af4bc439eb1572abe7000190d.json"}}, {"family": "Prost", "given": "Stefan", "initials": "S", "orcid": "0000-0002-6229-3596", "researcher": {"href": "https://publications.scilifelab.se/researcher/809ba200bb864ec9abf0d0cad09c5a42.json"}}, {"family": "Potapova", "given": "Olga", "initials": "O", "orcid": "0000-0002-3589-2489", "researcher": {"href": "https://publications.scilifelab.se/researcher/6a8a3f7d32434226be4d637673845820.json"}}, {"family": "Kirillova", "given": "Irina", "initials": "I"}, {"family": "Lister", "given": "Adrian M", "initials": "AM"}, {"family": "Heintzman", "given": "Peter D", "initials": "PD", "orcid": "0000-0002-6449-0219", "researcher": {"href": "https://publications.scilifelab.se/researcher/dd81ccff05904164be2bcceaa65422f7.json"}}, {"family": "Kapp", "given": "Joshua D", "initials": "JD"}, {"family": "Shapiro", "given": "Beth", "initials": "B"}, {"family": "Vartanyan", "given": "Sergey", "initials": "S"}, {"family": "G\u00f6therstr\u00f6m", "given": "Anders", "initials": "A", "orcid": "0000-0001-6307-8188", "researcher": {"href": "https://publications.scilifelab.se/researcher/2a1a0a680ab8456cbf5a941e9718fd5a.json"}}, {"family": "Dal\u00e9n", "given": "Love", "initials": "L", "orcid": "0000-0001-8270-7613", "researcher": {"href": "https://publications.scilifelab.se/researcher/48ecf726779249ac9d12f4f7a1cc62bf.json"}}], "type": "journal article", "published": "2020-10-05", "journal": {"title": "Curr. Biol.", "issn": "1879-0445", "volume": "30", "issue": "19", "pages": "3871-3879.e7", "issn-l": "0960-9822"}, "abstract": "Ancient DNA has significantly improved our understanding of the evolution and population history of extinct megafauna. However, few studies have used complete ancient genomes to examine species responses to climate change prior to extinction. The woolly rhinoceros (Coelodonta antiquitatis) was a cold-adapted megaherbivore widely distributed across northern Eurasia during the Late Pleistocene and became extinct approximately 14 thousand years before present (ka BP). While humans and climate change have been proposed as potential causes of extinction [1-3], knowledge is limited on how the woolly rhinoceros was impacted by human arrival and climatic fluctuations [2]. Here, we use one complete nuclear genome and 14 mitogenomes to investigate the demographic history of woolly rhinoceros leading up to its extinction. Unlike other northern megafauna, the effective population size of woolly rhinoceros likely increased at 29.7 ka BP and subsequently remained stable until close to the species' extinction. Analysis of the nuclear genome from a \u223c18.5-ka-old specimen did not indicate any increased inbreeding or reduced genetic diversity, suggesting that the population size remained steady for more than 13 ka following the arrival of humans [4]. The population contraction leading to extinction of the woolly rhinoceros may have thus been sudden and mostly driven by rapid warming in the B\u00f8lling-Aller\u00f8d interstadial. Furthermore, we identify woolly rhinoceros-specific adaptations to arctic climate, similar to those of the woolly mammoth. This study highlights how species respond differently to climatic fluctuations and further illustrates the potential of palaeogenomics to study the evolutionary history of extinct species.", "doi": "10.1016/j.cub.2020.07.046", "pmid": "32795436", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0960-9822(20)31071-X"}], "notes": [], "created": "2020-08-24T09:00:42.045Z", "modified": "2024-01-16T13:48:41.594Z"}, {"entity": "publication", "iuid": "e75a328b0c454c5db0f2f80fb863a92f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e75a328b0c454c5db0f2f80fb863a92f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e75a328b0c454c5db0f2f80fb863a92f"}}, "title": "HEARTBREAK Controls Post-translational Modification of INDEHISCENT to Regulate Fruit Morphology in Capsella.", "authors": [{"family": "Dong", "given": "Yang", "initials": "Y", "orcid": "0000-0003-2117-538X", "researcher": {"href": "https://publications.scilifelab.se/researcher/2aec5d6e4f0046dfa7e101dc45bee6d7.json"}}, {"family": "Majda", "given": "Mateusz", "initials": "M", "orcid": "0000-0003-3405-2901", "researcher": {"href": "https://publications.scilifelab.se/researcher/582d7b364d4d4442a7f470e52ed031bc.json"}}, {"family": "\u0160imura", "given": "Jan", "initials": "J"}, {"family": "Horvath", "given": "Robert", "initials": "R"}, {"family": "Srivastava", "given": "Anjil K", "initials": "AK", "orcid": "0000-0001-9871-5781", "researcher": {"href": "https://publications.scilifelab.se/researcher/7f1e429f187d483e86336b2733592b2a.json"}}, {"family": "\u0141angowski", "given": "\u0141ukasz", "initials": "\u0141"}, {"family": "Eldridge", "given": "Tilly", "initials": "T", "orcid": "0000-0003-1408-5001", "researcher": {"href": "https://publications.scilifelab.se/researcher/7feb9cd320e344e297bddc29826ccfd7.json"}}, {"family": "Stacey", "given": "Nicola", "initials": "N"}, {"family": "Slotte", "given": "Tanja", "initials": "T", "orcid": "0000-0001-6020-5102", "researcher": {"href": "https://publications.scilifelab.se/researcher/67c69ee78bae41478465a7e5fa63b946.json"}}, {"family": "Sadanandom", "given": "Ari", "initials": "A"}, {"family": "Ljung", "given": "Karin", "initials": "K"}, {"family": "Smith", "given": "Richard S", "initials": "RS"}, {"family": "\u00d8stergaard", "given": "Lars", "initials": "L"}], "type": "journal article", "published": "2020-10-05", "journal": {"title": "Curr. Biol.", "issn": "1879-0445", "volume": "30", "issue": "19", "pages": "3880-3888.e5", "issn-l": "0960-9822"}, "abstract": "Morphological variation is the basis of natural diversity and adaptation. For example, angiosperms (flowering plants) evolved during the Cretaceous period more than 100 mya and quickly colonized terrestrial habitats [1]. A major reason for their astonishing success was the formation of fruits, which exist in a myriad of different shapes and sizes [2]. Evolution of organ shape is fueled by variation in expression patterns of regulatory genes causing changes in anisotropic cell expansion and division patterns [3-5]. However, the molecular mechanisms that alter the polarity of growth to generate novel shapes are largely unknown. The heart-shaped fruits produced by members of the Capsella genus comprise an anatomical novelty, making it particularly well suited for studies on morphological diversification [6-8]. Here, we show that post-translational modification of regulatory proteins provides a critical step in organ-shape formation. Our data reveal that the SUMO protease, HEARTBREAK (HTB), from Capsella rubella controls the activity of the key regulator of fruit development, INDEHISCENT (CrIND in C. rubella), via de-SUMOylation. This post-translational modification initiates a transduction pathway required to ensure precisely localized auxin biosynthesis, thereby facilitating anisotropic cell expansion to ultimately form the heart-shaped Capsella fruit. Therefore, although variation in the expression of key regulatory genes is known to be a primary driver in morphological evolution, our work demonstrates how other processes-such as post-translational modification of one such regulator-affects organ morphology.", "doi": "10.1016/j.cub.2020.07.055", "pmid": "32795439", "labels": {"Swedish Metabolomics Centre": null}, "xrefs": [{"db": "pii", "key": "S0960-9822(20)31080-0"}, {"db": "pmc", "key": "PMC7544509"}], "notes": [], "created": "2020-12-11T11:56:12.239Z", "modified": "2025-10-17T13:03:16.627Z"}, {"entity": "publication", "iuid": "dbf4b623cec545a3bbfbdfe959dc2337", "links": {"self": {"href": "https://publications.scilifelab.se/publication/dbf4b623cec545a3bbfbdfe959dc2337.json"}, "display": {"href": "https://publications.scilifelab.se/publication/dbf4b623cec545a3bbfbdfe959dc2337"}}, "title": "A latent lineage potential in resident neural stem cells enables spinal cord repair.", "authors": [{"family": "Llorens-Bobadilla", "given": "Enric", "initials": "E", "orcid": "0000-0002-7891-1272", "researcher": {"href": "https://publications.scilifelab.se/researcher/3144601c466246cfa70acbe8c7ee00ee.json"}}, {"family": "Chell", "given": "James M", "initials": "JM", "orcid": "0000-0003-3019-4750", "researcher": {"href": "https://publications.scilifelab.se/researcher/5f42dee5363240b7ad5db1ec421d9932.json"}}, {"family": "Le Merre", "given": "Pierre", "initials": "P", "orcid": "0000-0003-4205-7411", "researcher": {"href": "https://publications.scilifelab.se/researcher/ba592e9aa93b433cb85ff11a786b0a71.json"}}, {"family": "Wu", "given": "Yicheng", "initials": "Y"}, {"family": "Zamboni", "given": "Margherita", "initials": "M", "orcid": "0000-0003-0664-4707", "researcher": {"href": "https://publications.scilifelab.se/researcher/1f196173b40b4819a5fcd11bf76a4e6e.json"}}, {"family": "Bergenstr\u00e5hle", "given": "Joseph", "initials": "J"}, {"family": "Stenudd", "given": "Moa", "initials": "M"}, {"family": "Sopova", "given": "Elena", "initials": "E", "orcid": "0000-0001-7561-331X", "researcher": {"href": "https://publications.scilifelab.se/researcher/49eae62ecbbf45848dc5d2808d363010.json"}}, {"family": "Lundeberg", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4313-1601", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a4e6ca0f29b4ead8569e2729481c3e0.json"}}, {"family": "Shupliakov", "given": "Oleg", "initials": "O", "orcid": "0000-0001-5352-6848", "researcher": {"href": "https://publications.scilifelab.se/researcher/136d6cd739f04017accb6198a9626a38.json"}}, {"family": "Carl\u00e9n", "given": "Marie", "initials": "M", "orcid": "0000-0003-1658-1631", "researcher": {"href": "https://publications.scilifelab.se/researcher/88931dd9e39c48e2820b89080c3945ad.json"}}, {"family": "Fris\u00e9n", "given": "Jonas", "initials": "J", "orcid": "0000-0001-5819-458X", "researcher": {"href": "https://publications.scilifelab.se/researcher/23064ee2ac9b4c2fb1eb94e61f92148e.json"}}], "type": "journal article", "published": "2020-10-02", "journal": {"title": "Science", "issn": "1095-9203", "issn-l": "0036-8075", "volume": "370", "issue": "6512", "pages": "eabb8795"}, "abstract": "Injuries to the central nervous system (CNS) are inefficiently repaired. Resident neural stem cells manifest a limited contribution to cell replacement. We have uncovered a latent potential in neural stem cells to replace large numbers of lost oligodendrocytes in the injured mouse spinal cord. Integrating multimodal single-cell analysis, we found that neural stem cells are in a permissive chromatin state that enables the unfolding of a normally latent gene expression program for oligodendrogenesis after injury. Ectopic expression of the transcription factor OLIG2 unveiled abundant stem cell-derived oligodendrogenesis, which followed the natural progression of oligodendrocyte differentiation, contributed to axon remyelination, and stimulated functional recovery of axon conduction. Recruitment of resident stem cells may thus serve as an alternative to cell transplantation after CNS injury.", "doi": "10.1126/science.abb8795", "pmid": "33004487", "labels": {"Eukaryotic Single Cell Genomics (ESCG)": "Service", "Integrated Microscopy Technologies Stockholm": "Service"}, "xrefs": [{"db": "pii", "key": "370/6512/eabb8795"}], "notes": [], "created": "2020-10-05T10:44:49.529Z", "modified": "2021-11-10T12:46:38.225Z"}, {"entity": "publication", "iuid": "8c2a6093b4864656bdafe542e02de9f8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8c2a6093b4864656bdafe542e02de9f8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8c2a6093b4864656bdafe542e02de9f8"}}, "title": "Notch activation in the mouse mammary luminal lineage leads to ductal hyperplasia and altered partitioning of luminal cell subtypes.", "authors": [{"family": "Phoon", "given": "Yee Peng", "initials": "YP"}, {"family": "Chivukula", "given": "Indira V", "initials": "IV"}, {"family": "Tsoi", "given": "Yat Long", "initials": "YL"}, {"family": "Kanatani", "given": "Shigeaki", "initials": "S"}, {"family": "Uhl\u00e9n", "given": "Per", "initials": "P"}, {"family": "Kuiper", "given": "Raoul", "initials": "R"}, {"family": "Lendahl", "given": "Urban", "initials": "U"}], "type": "journal article", "published": "2020-10-01", "journal": {"title": "Exp. Cell Res.", "issn": "1090-2422", "volume": "395", "issue": "1", "pages": "112156", "issn-l": "0014-4827"}, "abstract": "Hyperactivated Notch signalling has been implicated in breast cancer, but how elevated levels of Notch signalling contribute to mammary dysplasia and tumorigenesis is not fully understood. In this study, we express an activated form of Notch1 in the mouse mammary luminal lineage and analyse the consequences for tumour formation and the transcriptomic landscape in the luminal lineage. Simultaneous conditional activation of a Notch1 intracellular domain (Notch1 ICD) and EGFP in the luminal lineage was achieved by removal of a stop cassette by CRE-recombinase expression from the whey acidic protein (WAP) promoter. Mice in which Notch1 ICD was activated in the luminal lineage (WAP-CRE;R26-N1ICD mice) exhibit ductal hyperplasia after lactation with an increase in branching frequency and in the number of side-branch ends in the ductal tree. A subset of the mice developed mammary tumours and the majority of the tumour cells expressed EGFP (as a proxy for Notch1 ICD), indicating that the tumours originate from the Notch1 ICD-expressing cells. Single-cell transcriptome analysis of the EGFP-positive mammary cells identified six subtypes of luminal cells. The same six subtypes were found in control mice (WAP-CRE;R26-tdTomato mice expressing the tdTomato reporter from WAP-CRE-mediated activation), but the proportion of cells in the various subtypes differed between the WAP-CRE;R26-N1ICD and control WAP-CRE;R26-tdTomato mice. In conclusion, we show that Notch1 ICD expression in the luminal lineage produces a ductal hyperplasia and branching phenotype accompanied by altered luminal cell subtype partitioning.", "doi": "10.1016/j.yexcr.2020.112156", "pmid": "32707133", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S0014-4827(20)30403-1"}], "notes": [], "created": "2020-12-07T16:34:36.716Z", "modified": "2024-01-16T13:48:41.602Z"}, {"entity": "publication", "iuid": "c4ca7ddb792e49aab70137c27e6970f3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c4ca7ddb792e49aab70137c27e6970f3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c4ca7ddb792e49aab70137c27e6970f3"}}, "title": "Large-scale targeted sequencing identifies risk genes for neurodevelopmental disorders.", "authors": [{"family": "Wang", "given": "Tianyun", "initials": "T", "orcid": "0000-0002-5179-087X", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f8343adbdf84296a4bf04c6890d49d2.json"}}, {"family": "Hoekzema", "given": "Kendra", "initials": "K"}, {"family": "Vecchio", "given": "Davide", "initials": "D", "orcid": "0000-0003-2907-3206", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7d64eefa6a041caad3a8c860e76d84e.json"}}, {"family": "Wu", "given": "Huidan", "initials": "H"}, {"family": "Sulovari", "given": "Arvis", "initials": "A", "orcid": "0000-0003-4354-9020", "researcher": {"href": "https://publications.scilifelab.se/researcher/85f6043d9c7c4ca49ced9ed1c0f97340.json"}}, {"family": "Coe", "given": "Bradley P", "initials": "BP"}, {"family": "Gillentine", "given": "Madelyn A", "initials": "MA", "orcid": "0000-0002-8989-2214", "researcher": {"href": "https://publications.scilifelab.se/researcher/9e5086e94ffb4bc7a8367b15d17b876e.json"}}, {"family": "Wilfert", "given": "Amy B", "initials": "AB"}, {"family": "Perez-Jurado", "given": "Luis A", "initials": "LA"}, {"family": "Kvarnung", "given": "Malin", "initials": "M"}, {"family": "Sleyp", "given": "Yoeri", "initials": "Y"}, {"family": "Earl", "given": "Rachel K", "initials": "RK"}, {"family": "Rosenfeld", "given": "Jill A", "initials": "JA", "orcid": "0000-0001-5664-7987", "researcher": {"href": "https://publications.scilifelab.se/researcher/1826b4a473304149a22a9646d6f76a3e.json"}}, {"family": "Geisheker", "given": "Madeleine R", "initials": "MR", "orcid": "0000-0002-4166-3236", "researcher": {"href": "https://publications.scilifelab.se/researcher/e3494f8f657c4d0fbbd886ac89ac9cfa.json"}}, {"family": "Han", "given": "Lin", "initials": "L"}, {"family": "Du", "given": "Bing", "initials": "B"}, {"family": "Barnett", "given": "Chris", "initials": "C"}, {"family": "Thompson", "given": "Elizabeth", "initials": "E"}, {"family": "Shaw", "given": "Marie", "initials": "M"}, {"family": "Carroll", "given": "Renee", "initials": "R"}, {"family": "Friend", "given": "Kathryn", "initials": "K"}, {"family": "Catford", "given": "Rachael", "initials": "R"}, {"family": "Palmer", "given": "Elizabeth E", "initials": "EE"}, {"family": "Zou", "given": "Xiaobing", "initials": "X"}, {"family": "Ou", "given": "Jianjun", "initials": "J"}, {"family": "Li", "given": "Honghui", "initials": "H"}, {"family": "Guo", "given": "Hui", "initials": "H", "orcid": "0000-0002-1570-2545", "researcher": {"href": "https://publications.scilifelab.se/researcher/2b7e6c55e24449fd9b53f6ed08003742.json"}}, {"family": "Gerdts", "given": "Jennifer", "initials": "J"}, {"family": "Avola", "given": "Emanuela", "initials": "E"}, {"family": "Calabrese", "given": "Giuseppe", "initials": "G"}, {"family": "Elia", "given": "Maurizio", "initials": "M"}, {"family": "Greco", "given": "Donatella", "initials": "D"}, {"family": "Lindstrand", "given": "Anna", "initials": "A", "orcid": "0000-0003-0806-5602", "researcher": {"href": "https://publications.scilifelab.se/researcher/07f3e6152da043d38c7a81974fcf8c23.json"}}, {"family": "Nordgren", "given": "Ann", "initials": "A", "orcid": "0000-0003-3285-4281", "researcher": {"href": "https://publications.scilifelab.se/researcher/08e74c6ddc27493696beca0883027cdd.json"}}, {"family": "Anderlid", "given": "Britt-Marie", "initials": "BM"}, {"family": "Vandeweyer", "given": "Geert", "initials": "G"}, {"family": "Van Dijck", "given": "Anke", "initials": "A", "orcid": "0000-0002-6713-2943", "researcher": {"href": "https://publications.scilifelab.se/researcher/b190da43c29e4245b71b37ab7cdb81db.json"}}, {"family": "Van der Aa", "given": "Nathalie", "initials": "N"}, {"family": "McKenna", "given": "Brooke", "initials": "B"}, {"family": "Hancarova", "given": "Miroslava", "initials": "M"}, {"family": "Bendova", "given": "Sarka", "initials": "S"}, {"family": "Havlovicova", "given": "Marketa", "initials": "M"}, {"family": "Malerba", "given": "Giovanni", "initials": "G"}, {"family": "Bernardina", "given": "Bernardo Dalla", "initials": "BD"}, {"family": "Muglia", "given": "Pierandrea", "initials": "P"}, {"family": "van Haeringen", "given": "Arie", "initials": "A"}, {"family": "Hoffer", "given": "Mariette J V", "initials": "MJV", "orcid": "0000-0002-1812-7670", "researcher": {"href": "https://publications.scilifelab.se/researcher/04747e9661474d43a1f4a7ed51eb7207.json"}}, {"family": "Franke", "given": "Barbara", "initials": "B", "orcid": "0000-0003-4375-6572", "researcher": {"href": "https://publications.scilifelab.se/researcher/105f0131cfc34a668ed840e622e4f902.json"}}, {"family": "Cappuccio", "given": "Gerarda", "initials": "G"}, {"family": "Delatycki", "given": "Martin", "initials": "M"}, {"family": "Lockhart", "given": "Paul J", "initials": "PJ", "orcid": "0000-0003-2531-8413", "researcher": {"href": "https://publications.scilifelab.se/researcher/af606d21d6524fbdbd65f044fddbd00b.json"}}, {"family": "Manning", "given": "Melanie A", "initials": "MA"}, {"family": "Liu", "given": "Pengfei", "initials": "P", "orcid": "0000-0002-4177-709X", "researcher": {"href": "https://publications.scilifelab.se/researcher/8bda9fff7cc042eaa054b5257799c1f4.json"}}, {"family": "Scheffer", "given": "Ingrid E", "initials": "IE"}, {"family": "Brunetti-Pierri", "given": "Nicola", "initials": "N", "orcid": "0000-0002-6895-8819", "researcher": {"href": "https://publications.scilifelab.se/researcher/c9785f9985d645259283e808cdcd77a9.json"}}, {"family": "Rommelse", "given": "Nanda", "initials": "N"}, {"family": "Amaral", "given": "David G", "initials": "DG"}, {"family": "Santen", "given": "Gijs W E", "initials": "GWE"}, {"family": "Trabetti", "given": "Elisabetta", "initials": "E"}, {"family": "Sedl\u00e1\u010dek", "given": "Zden\u011bk", "initials": "Z"}, {"family": "Michaelson", "given": "Jacob J", "initials": "JJ", "orcid": "0000-0001-9713-0992", "researcher": {"href": "https://publications.scilifelab.se/researcher/13cd0bf6a3c3437485c0c8c6a32839dc.json"}}, {"family": "Pierce", "given": "Karen", "initials": "K"}, {"family": "Courchesne", "given": "Eric", "initials": "E", "orcid": "0000-0002-3772-5799", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae6305c8ed044e1ca6b637f982d181c4.json"}}, {"family": "Kooy", "given": "R Frank", "initials": "RF", "orcid": "0000-0003-2024-0485", "researcher": {"href": "https://publications.scilifelab.se/researcher/d0e9d246a6ac47029258886b9537a0e5.json"}}, {"family": "SPARK Consortium", "given": "", "initials": ""}, {"family": "Nordenskj\u00f6ld", "given": "Magnus", "initials": "M"}, {"family": "Romano", "given": "Corrado", "initials": "C", "orcid": "0000-0003-1049-0683", "researcher": {"href": "https://publications.scilifelab.se/researcher/634b98b512e84042af68e05eff055978.json"}}, {"family": "Peeters", "given": "Hilde", "initials": "H"}, {"family": "Bernier", "given": "Raphael A", "initials": "RA"}, {"family": "Gecz", "given": "Jozef", "initials": "J", "orcid": "0000-0002-7884-6861", "researcher": {"href": "https://publications.scilifelab.se/researcher/dfa0d2adb36840858e1f9f8e407269b0.json"}}, {"family": "Xia", "given": "Kun", "initials": "K", "orcid": "0000-0001-8090-6002", "researcher": {"href": "https://publications.scilifelab.se/researcher/bbfe349e05c740a7894d1bab511a3768.json"}}, {"family": "Eichler", "given": "Evan E", "initials": "EE", "orcid": "0000-0002-8246-4014", "researcher": {"href": "https://publications.scilifelab.se/researcher/43901cc9fc3b4f5c9a18260e36558eb9.json"}}], "type": "journal article", "published": "2020-10-01", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "11", "issue": "1", "pages": "4932", "issn-l": "2041-1723"}, "abstract": "Most genes associated with neurodevelopmental disorders (NDDs) were identified with an excess of de novo mutations (DNMs) but the significance in case-control mutation burden analysis is unestablished. Here, we sequence 63 genes in 16,294 NDD cases and an additional 62 genes in 6,211 NDD cases. By combining these with published data, we assess a total of 125 genes in over 16,000 NDD cases and compare the mutation burden to nonpsychiatric controls from ExAC. We identify 48 genes (25 newly reported) showing significant burden of ultra-rare (MAF < 0.01%) gene-disruptive mutations (FDR 5%), six of which reach family-wise error rate (FWER) significance (p < 1.25E-06). Among these 125 targeted genes, we also reevaluate DNM excess in 17,426 NDD trios with 6,499 new autism trios. We identify 90 genes enriched for DNMs (FDR 5%; e.g., GABRG2 and UIMC1); of which, 61 reach FWER significance (p < 3.64E-07; e.g., CASZ1). In addition to doubling the number of patients for many NDD risk genes, we present phenotype-genotype correlations for seven risk genes (CTCF, HNRNPU, KCNQ3, ZBTB18, TCF12, SPEN, and LEO1) based on this large-scale targeted sequencing effort.", "doi": "10.1038/s41467-020-18723-y", "pmid": "33004838", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-18723-y"}, {"db": "pmc", "key": "PMC7530681"}], "notes": [], "created": "2021-11-20T12:18:30.540Z", "modified": "2021-11-20T12:18:31.111Z"}, {"entity": "publication", "iuid": "26891b7047fe4d50971760420593e083", "links": {"self": {"href": "https://publications.scilifelab.se/publication/26891b7047fe4d50971760420593e083.json"}, "display": {"href": "https://publications.scilifelab.se/publication/26891b7047fe4d50971760420593e083"}}, "title": "Khoe-San Genomes Reveal Unique Variation and Confirm the Deepest Population Divergence in Homo sapiens.", "authors": [{"family": "Schlebusch", "given": "Carina M", "initials": "CM", "orcid": "0000-0002-8160-9621", "researcher": {"href": "https://publications.scilifelab.se/researcher/682f10853c1145649b8c76680605dd9b.json"}}, {"family": "Sj\u00f6din", "given": "Per", "initials": "P"}, {"family": "Breton", "given": "Gwenna", "initials": "G", "orcid": "0000-0002-4100-9963", "researcher": {"href": "https://publications.scilifelab.se/researcher/757353d5314b4c20ac2ef4833dd207d9.json"}}, {"family": "G\u00fcnther", "given": "Torsten", "initials": "T"}, {"family": "Naidoo", "given": "Thijessen", "initials": "T"}, {"family": "Hollfelder", "given": "Nina", "initials": "N"}, {"family": "Sj\u00f6strand", "given": "Agnes E", "initials": "AE"}, {"family": "Xu", "given": "Jingzi", "initials": "J"}, {"family": "Gattepaille", "given": "Lucie M", "initials": "LM"}, {"family": "Vicente", "given": "M\u00e1rio", "initials": "M"}, {"family": "Scofield", "given": "Douglas G", "initials": "DG", "orcid": "0000-0001-5235-6461", "researcher": {"href": "https://publications.scilifelab.se/researcher/62a8063a48a446a7947d55f9900894a6.json"}}, {"family": "Malmstr\u00f6m", "given": "Helena", "initials": "H"}, {"family": "de Jongh", "given": "Michael", "initials": "M"}, {"family": "Lombard", "given": "Marlize", "initials": "M", "orcid": "0000-0002-0675-0414", "researcher": {"href": "https://publications.scilifelab.se/researcher/e04e97bbc9914f358864988174b9b58d.json"}}, {"family": "Soodyall", "given": "Himla", "initials": "H"}, {"family": "Jakobsson", "given": "Mattias", "initials": "M", "orcid": "0000-0001-7840-7853", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a4abe0fcb20492d9ec849c9fbf58a71.json"}}], "type": "journal article", "published": "2020-10-01", "journal": {"title": "Mol. Biol. Evol.", "issn": "1537-1719", "issn-l": "0737-4038", "volume": "37", "issue": "10", "pages": "2944-2954"}, "abstract": "The southern African indigenous Khoe-San populations harbor the most divergent lineages of all living peoples. Exploring their genomes is key to understanding deep human history. We sequenced 25 full genomes from five Khoe-San populations, revealing many novel variants, that 25% of variants are unique to the Khoe-San, and that the Khoe-San group harbors the greatest level of diversity across the globe. In line with previous studies, we found several gene regions with extreme values in genome-wide scans for selection, potentially caused by natural selection in the lineage leading to Homo sapiens and more recent in time. These gene regions included immunity-, sperm-, brain-, diet-, and muscle-related genes. When accounting for recent admixture, all Khoe-San groups display genetic diversity approaching the levels in other African groups and a reduction in effective population size starting around 100,000 years ago. Hence, all human groups show a reduction in effective population size commencing around the time of the Out-of-Africa migrations, which coincides with changes in the paleoclimate records, changes that potentially impacted all humans at the time.", "doi": "10.1093/molbev/msaa140", "pmid": "32697301", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "5874945"}, {"db": "pmc", "key": "PMC7530619"}], "notes": [], "created": "2020-12-08T23:26:14.491Z", "modified": "2024-01-16T13:48:41.609Z"}, {"entity": "publication", "iuid": "154532dd2cc14c359aedcbc68f77a29c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/154532dd2cc14c359aedcbc68f77a29c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/154532dd2cc14c359aedcbc68f77a29c"}}, "title": "Brain Transcriptomics of Wild and Domestic Rabbits Suggests That Changes in Dopamine Signaling and Ciliary Function Contributed to Evolution of Tameness.", "authors": [{"family": "Sato", "given": "Daiki X", "initials": "DX", "orcid": "0000-0002-9527-8253", "researcher": {"href": "https://publications.scilifelab.se/researcher/7ad2eafb0bce4d2ba7c4f9cf7ed05eac.json"}}, {"family": "Rafati", "given": "Nima", "initials": "N", "orcid": "0000-0002-3687-9745", "researcher": {"href": "https://publications.scilifelab.se/researcher/8b5c32bab72f430a80485c0312ca0e21.json"}}, {"family": "Ring", "given": "Henrik", "initials": "H"}, {"family": "Younis", "given": "Shady", "initials": "S"}, {"family": "Feng", "given": "Chungang", "initials": "C"}, {"family": "Blanco-Aguiar", "given": "Jos\u00e9 A", "initials": "JA"}, {"family": "Rubin", "given": "Carl-Johan", "initials": "CJ"}, {"family": "Villafuerte", "given": "Rafael", "initials": "R"}, {"family": "Hallb\u00f6\u00f6k", "given": "Finn", "initials": "F", "orcid": "0000-0001-7552-187X", "researcher": {"href": "https://publications.scilifelab.se/researcher/6fd6bad55b67431c82e2e54e5b007917.json"}}, {"family": "Carneiro", "given": "Miguel", "initials": "M"}, {"family": "Andersson", "given": "Leif", "initials": "L", "orcid": "0000-0002-4085-6968", "researcher": {"href": "https://publications.scilifelab.se/researcher/bd3343c12f994b1fabcae23027d3a76d.json"}}], "type": "comparative study", "published": "2020-10-01", "journal": {"title": "Genome Biol Evol", "issn": "1759-6653", "volume": "12", "issue": "10", "pages": "1918-1928", "issn-l": "1759-6653"}, "abstract": "Domestication has resulted in immense phenotypic changes in animals despite their relatively short evolutionary history. The European rabbit is one of the most recently domesticated animals, but exhibits distinct morphological, physiological, and behavioral differences from their wild conspecifics. A previous study revealed that sequence variants with striking allele frequency differences between wild and domestic rabbits were enriched in conserved noncoding regions, in the vicinity of genes involved in nervous system development. This suggests that a large proportion of the genetic changes targeted by selection during domestication might affect gene regulation. Here, we generated RNA-sequencing data for four brain regions (amygdala, hypothalamus, hippocampus, and parietal/temporal cortex) sampled at birth and revealed hundreds of differentially expressed genes (DEGs) between wild and domestic rabbits. DEGs in amygdala were significantly enriched for genes associated with dopaminergic function and all 12 DEGs in this category showed higher expression in domestic rabbits. DEGs in hippocampus were enriched for genes associated with ciliary function, all 21 genes in this category showed lower expression in domestic rabbits. These results indicate an important role of dopamine signaling and ciliary function in the evolution of tameness during rabbit domestication. Our study shows that gene expression in specific pathways has been profoundly altered during domestication, but that the majority of genes showing differential expression in this study have not been the direct targets of selection.", "doi": "10.1093/gbe/evaa158", "pmid": "32835359", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Service", "National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "5896528"}, {"db": "pmc", "key": "PMC7594241"}], "notes": [], "created": "2020-09-15T07:00:59.512Z", "modified": "2024-01-16T13:48:41.617Z"}, {"entity": "publication", "iuid": "146c61589294400ca507989d19c6b16a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/146c61589294400ca507989d19c6b16a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/146c61589294400ca507989d19c6b16a"}}, "title": "A Repertory of Rearrangements and the Loss of an Inverted Repeat Region in Passiflora Chloroplast Genomes.", "authors": [{"family": "Cauz-Santos", "given": "Luiz Augusto", "initials": "LA"}, {"family": "da Costa", "given": "Zirlane Portugal", "initials": "ZP"}, {"family": "Callot", "given": "Caroline", "initials": "C"}, {"family": "Cauet", "given": "St\u00e9phane", "initials": "S"}, {"family": "Zucchi", "given": "Maria Imaculada", "initials": "MI"}, {"family": "Berg\u00e8s", "given": "H\u00e9l\u00e8ne", "initials": "H"}, {"family": "van den Berg", "given": "C\u00e1ssio", "initials": "C"}, {"family": "Vieira", "given": "Maria Lucia Carneiro", "initials": "MLC", "orcid": "0000-0003-0341-5714", "researcher": {"href": "https://publications.scilifelab.se/researcher/8eb37815cd9e4577b677fd053bf6e15c.json"}}], "type": "comparative study", "published": "2020-10-01", "journal": {"title": "Genome Biol Evol", "issn": "1759-6653", "volume": "12", "issue": "10", "pages": "1841-1857", "issn-l": "1759-6653"}, "abstract": "Chloroplast genomes (cpDNA) in angiosperms are usually highly conserved. Although rearrangements have been observed in some lineages, such as Passiflora, the mechanisms that lead to rearrangements are still poorly elucidated. In the present study, we obtained 20 new chloroplast genomes (18 species from the genus Passiflora, and Dilkea retusa and Mitostemma brevifilis from the family Passifloraceae) in order to investigate cpDNA evolutionary history in this group. Passiflora cpDNAs vary in size considerably, with \u223c50 kb between shortest and longest. Large inverted repeat (IR) expansions were identified, and at the extreme opposite, the loss of an IR was detected for the first time in Passiflora, a rare event in angiosperms. The loss of an IR region was detected in Passiflora capsularis and Passiflora costaricensis, a species in which occasional biparental chloroplast inheritance has previously been reported. A repertory of rearrangements such as inversions and gene losses were detected, making Passiflora one of the few groups with complex chloroplast genome evolution. We also performed a phylogenomic study based on all the available cp genomes and our analysis implies that there is a need to reconsider the taxonomic classifications of some species in the group.", "doi": "10.1093/gbe/evaa155", "pmid": "32722748", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service"}, "xrefs": [{"db": "pii", "key": "5877432"}, {"db": "pmc", "key": "PMC7586853"}], "notes": [], "created": "2020-08-25T13:00:50.882Z", "modified": "2021-11-10T12:46:41.641Z"}, {"entity": "publication", "iuid": "4fe1c1c64da447edb1c83d2c5f3923ec", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4fe1c1c64da447edb1c83d2c5f3923ec.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4fe1c1c64da447edb1c83d2c5f3923ec"}}, "title": "Unraveling the Immune Response in Severe COVID-19.", "authors": [{"family": "Rodriguez", "given": "Lucie", "initials": "L"}, {"family": "Brodin", "given": "Petter", "initials": "P", "orcid": "0000-0002-8103-0046", "researcher": {"href": "https://publications.scilifelab.se/researcher/40097353cdb24e52bf2330eb687042bf.json"}}], "type": "editorial", "published": "2020-10-00", "journal": {"title": "J Clin Immunol", "issn": "1573-2592", "issn-l": "0271-9142", "volume": "40", "issue": "7", "pages": "958-959"}, "abstract": null, "doi": "10.1007/s10875-020-00849-9", "pmid": "32827284", "labels": {"Cellular Immunomonitoring": "Technology development", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1007/s10875-020-00849-9"}, {"db": "pmc", "key": "PMC7442888"}], "notes": [], "created": "2020-08-23T20:17:38.694Z", "modified": "2024-01-16T13:48:41.638Z"}, {"entity": "publication", "iuid": "bb0b805b5429464ab0bddbb9a6f7787e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bb0b805b5429464ab0bddbb9a6f7787e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bb0b805b5429464ab0bddbb9a6f7787e"}}, "title": "Profiles of histidine-rich glycoprotein associate with age and risk of all-cause mortality.", "authors": [{"family": "Hong", "given": "Mun-Gwan", "initials": "MG", "orcid": "0000-0001-8603-8293", "researcher": {"href": "https://publications.scilifelab.se/researcher/5d66c199ece143a6ab15222d8b55e3ea.json"}}, {"family": "Dodig-Crnkovi\u0107", "given": "Tea", "initials": "T", "orcid": "0000-0002-2875-896X", "researcher": {"href": "https://publications.scilifelab.se/researcher/cf18af5b676b449693945249fc1767e4.json"}}, {"family": "Chen", "given": "Xu", "initials": "X"}, {"family": "Drobin", "given": "Kimi", "initials": "K"}, {"family": "Lee", "given": "Woojoo", "initials": "W"}, {"family": "Wang", "given": "Yunzhang", "initials": "Y"}, {"family": "Edfors", "given": "Fredrik", "initials": "F"}, {"family": "Kotol", "given": "David", "initials": "D", "orcid": "0000-0002-5388-3826", "researcher": {"href": "https://publications.scilifelab.se/researcher/085cca6e87fb4639b720b0e5c8c1da2a.json"}}, {"family": "Thomas", "given": "Cecilia Engel", "initials": "CE", "orcid": "0000-0001-6201-6380", "researcher": {"href": "https://publications.scilifelab.se/researcher/3a1156f987764218af202efbd76c31fd.json"}}, {"family": "Sj\u00f6berg", "given": "Ronald", "initials": "R", "orcid": "0000-0003-1363-5796", "researcher": {"href": "https://publications.scilifelab.se/researcher/d08326da26da422ab445a26563843e79.json"}}, {"family": "Odeberg", "given": "Jacob", "initials": "J", "orcid": "0000-0003-0996-1644", "researcher": {"href": "https://publications.scilifelab.se/researcher/d1f04395fea84d898a8fe2a9875e79c4.json"}}, {"family": "Hamsten", "given": "Anders", "initials": "A"}, {"family": "Silveira", "given": "Angela", "initials": "A", "orcid": "0000-0003-2063-4935", "researcher": {"href": "https://publications.scilifelab.se/researcher/6fd1197769804dd48b9de86f11340ef2.json"}}, {"family": "Hall", "given": "Per", "initials": "P", "orcid": "0000-0002-5640-9126", "researcher": {"href": "https://publications.scilifelab.se/researcher/5e177f5d95f34b148064662f34ef6660.json"}}, {"family": "Nilsson", "given": "Peter", "initials": "P", "orcid": "0000-0002-4657-8532", "researcher": {"href": "https://publications.scilifelab.se/researcher/799bcf1cf8cf451296f4535dd4ca9dc0.json"}}, {"family": "Pawitan", "given": "Yudi", "initials": "Y"}, {"family": "Uhl\u00e9n", "given": "Mathias", "initials": "M", "orcid": "0000-0002-4858-8056", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff81da3cb0cf4262873b993a1b06798c.json"}}, {"family": "Pedersen", "given": "Nancy L", "initials": "NL"}, {"family": "H\u00e4gg", "given": "Sara", "initials": "S"}, {"family": "Magnusson", "given": "Patrik Ke", "initials": "PK"}, {"family": "Schwenk", "given": "Jochen M", "initials": "JM", "orcid": "0000-0001-8141-8449", "researcher": {"href": "https://publications.scilifelab.se/researcher/aba5822711b246b397fffacb7ae403b3.json"}}], "type": "journal article", "published": "2020-10-00", "journal": {"title": "Life Sci. Alliance", "issn": "2575-1077", "issn-l": "2575-1077", "volume": "3", "issue": "10", "pages": "e202000817"}, "abstract": "Despite recognizing aging as a common risk factor of many human diseases, little is known about its molecular traits. To identify age-associated proteins circulating in human blood, we screened 156 individuals aged 50-92 using exploratory and multiplexed affinity proteomics assays. Profiling eight additional study sets (N = 3,987), performing antibody validation, and conducting a meta-analysis revealed a consistent age association (P = 6.61 \u00d7 10-6) for circulating histidine-rich glycoprotein (HRG). Sequence variants of HRG influenced how the protein was recognized in the immunoassays. Indeed, only the HRG profiles affected by rs9898 were associated with age and predicted the risk of mortality (HR = 1.25 per SD; 95% CI = 1.12-1.39; P = 6.45 \u00d7 10-5) during a follow-up period of 8.5 yr after blood sampling (IQR = 7.7-9.3 yr). Our affinity proteomics analysis found associations between the particular molecular traits of circulating HRG with age and all-cause mortality. The distinct profiles of this multipurpose protein could serve as an accessible and informative indicator of the physiological processes related to biological aging.", "doi": "10.26508/lsa.202000817", "pmid": "32737166", "labels": {"Autoimmunity and Serology Profiling": "Service", "Affinity Proteomics Stockholm": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "3/10/e202000817"}, {"db": "pmc", "key": "PMC7409555"}], "notes": [], "created": "2020-08-21T08:30:48.217Z", "modified": "2024-01-16T13:48:41.646Z"}, {"entity": "publication", "iuid": "b18e9f266ef54cc9a8acdfa3763884a1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b18e9f266ef54cc9a8acdfa3763884a1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b18e9f266ef54cc9a8acdfa3763884a1"}}, "title": "Ouabain Modulates the Functional Interaction Between Na,K-ATPase and NMDA Receptor.", "authors": [{"family": "Akkuratov", "given": "Evgeny E", "initials": "EE"}, {"family": "Westin", "given": "Linda", "initials": "L"}, {"family": "Vazquez-Juarez", "given": "Erika", "initials": "E"}, {"family": "de Marothy", "given": "Minttu", "initials": "M"}, {"family": "Melnikova", "given": "Aleksandra K", "initials": "AK"}, {"family": "Blom", "given": "Hans", "initials": "H", "orcid": "0000-0002-5584-9170", "researcher": {"href": "https://publications.scilifelab.se/researcher/3ce356a74dc84e0ea6af85397f11d869.json"}}, {"family": "Lindskog", "given": "Maria", "initials": "M"}, {"family": "Brismar", "given": "Hjalmar", "initials": "H", "orcid": "0000-0003-0578-4003", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ec23336e2ef4e298f340876f1136dce.json"}}, {"family": "Aperia", "given": "Anita", "initials": "A"}], "type": "journal article", "published": "2020-10-00", "journal": {"title": "Mol Neurobiol", "issn": "1559-1182", "volume": "57", "issue": "10", "pages": "4018-4030", "issn-l": "0893-7648"}, "abstract": "The N-methyl-D-aspartate (NMDA) receptor plays an essential role in glutamatergic transmission and synaptic plasticity and researchers are seeking for different modulators of NMDA receptor function. One possible mechanism for its regulation could be through adjacent membrane proteins. NMDA receptors coprecipitate with Na,K-ATPase, indicating a potential interaction of these two proteins. Ouabain, a mammalian cardiotonic steroid that specifically binds to Na,K-ATPase and affects its conformation, can protect from some toxic effects of NMDA receptor activation. Here we have examined whether NMDA receptor activity and downstream effects can be modulated by physiological ouabain concentrations. The spatial colocalization between NMDA receptors and the Na,K-ATPase catalytic subunits on dendrites of cultured rat hippocampal neurons was analyzed with super-resolution dSTORM microscopy. The functional interaction was analyzed with calcium imaging of single hippocampal neurons exposed to 10 \u03bcM NMDA in presence and absence of ouabain and by determination of the ouabain effect on NMDA receptor-dependent long-term potentiation. We show that NMDA receptors and the Na,K-ATPase catalytic subunits alpha1 and alpha3 exist in same protein complex and that ouabain in nanomolar concentration consistently reduces the calcium response to NMDA. Downregulation of the NMDA response is not associated with internalization of the receptor or with alterations in its state of Src phosphorylation. Ouabain in nanomolar concentration elicits a long-term potentiation response. Our findings suggest that ouabain binding to a fraction of Na,K-ATPase molecules that cluster with the NMDA receptors will, via a conformational effect on the NMDA receptors, cause moderate but consistent reduction of NMDA receptor response at synaptic activation.", "doi": "10.1007/s12035-020-01984-5", "pmid": "32651756", "labels": {"Integrated Microscopy Technologies Stockholm": "Technology development"}, "xrefs": [{"db": "pii", "key": "10.1007/s12035-020-01984-5"}, {"db": "pmc", "key": "PMC7467916"}], "notes": [], "created": "2020-07-28T09:26:36.444Z", "modified": "2021-11-10T12:46:45.269Z"}, {"entity": "publication", "iuid": "55650e8e623a4729a2bed5738fe75020", "links": {"self": {"href": "https://publications.scilifelab.se/publication/55650e8e623a4729a2bed5738fe75020.json"}, "display": {"href": "https://publications.scilifelab.se/publication/55650e8e623a4729a2bed5738fe75020"}}, "title": "Multi-Reader-Multi-Split Annotation of Emphysema in Computed Tomography.", "authors": [{"family": "Lid\u00e9n", "given": "Mats", "initials": "M", "orcid": "0000-0002-1346-1450", "researcher": {"href": "https://publications.scilifelab.se/researcher/d34571b90c6b4611991944963b3e3dc8.json"}}, {"family": "Hjelmgren", "given": "Ola", "initials": "O"}, {"family": "Vikgren", "given": "Jenny", "initials": "J"}, {"family": "Thunberg", "given": "Per", "initials": "P"}], "type": "journal article", "published": "2020-10-00", "journal": {"title": "J Digit Imaging", "issn": "1618-727X", "volume": "33", "issue": "5", "pages": "1185-1193", "issn-l": null}, "abstract": "Emphysema is visible on computed tomography (CT) as low-density lesions representing the destruction of the pulmonary alveoli. To train a machine learning model on the emphysema extent in CT images, labeled image data is needed. The provision of these labels requires trained readers, who are a limited resource. The purpose of the study was to test the reading time, inter-observer reliability and validity of the multi-reader-multi-split method for acquiring CT image labels from radiologists. The approximately 500 slices of each stack of lung CT images were split into 1-cm chunks, with 17 thin axial slices per chunk. The chunks were randomly distributed to 26 readers, radiologists and radiology residents. Each chunk was given a quick score concerning emphysema type and severity in the left and right lung separately. A cohort of 102 subjects, with varying degrees of visible emphysema in the lung CT images, was selected from the SCAPIS pilot, performed in 2012 in Gothenburg, Sweden. In total, the readers created 9050 labels for 2881 chunks. Image labels were compared with regional annotations already provided at the SCAPIS pilot inclusion. The median reading time per chunk was 15 s. The inter-observer Krippendorff's alpha was 0.40 and 0.53 for emphysema type and score, respectively, and higher in the apical part than in the basal part of the lungs. The multi-split emphysema scores were generally consistent with regional annotations. In conclusion, the multi-reader-multi-split method provided reasonably valid image labels, with an estimation of the inter-observer reliability.", "doi": "10.1007/s10278-020-00378-2", "pmid": "32779016", "labels": {"AIDA Data Hub": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7572947"}, {"db": "pii", "key": "10.1007/s10278-020-00378-2"}], "notes": [], "created": "2023-05-25T15:52:51.149Z", "modified": "2023-05-25T15:52:51.188Z"}, {"entity": "publication", "iuid": "72147ced3fdc4fc880cf503299e1da36", "links": {"self": {"href": "https://publications.scilifelab.se/publication/72147ced3fdc4fc880cf503299e1da36.json"}, "display": {"href": "https://publications.scilifelab.se/publication/72147ced3fdc4fc880cf503299e1da36"}}, "title": "Mitigation of the replication of SARS-CoV-2 by nitric oxide in vitro.", "authors": [{"family": "Akaberi", "given": "Dario", "initials": "D"}, {"family": "Krambrich", "given": "Janina", "initials": "J", "orcid": "0000-0002-5061-7143", "researcher": {"href": "https://publications.scilifelab.se/researcher/b518bebea7364c1ba1806a1952596ec0.json"}}, {"family": "Ling", "given": "Jiaxin", "initials": "J"}, {"family": "Luni", "given": "Chen", "initials": "C"}, {"family": "Hedenstierna", "given": "G\u00f6ran", "initials": "G"}, {"family": "J\u00e4rhult", "given": "Josef D", "initials": "JD"}, {"family": "Lennerstrand", "given": "Johan", "initials": "J"}, {"family": "Lundkvist", "given": "\u00c5ke", "initials": "\u00c5"}], "type": "journal article", "published": "2020-10-00", "journal": {"title": "Redox Biol", "issn": "2213-2317", "issn-l": null, "volume": "37", "issue": null, "pages": "101734"}, "abstract": "The ongoing SARS-CoV-2 pandemic is a global public health emergency posing a high burden on nations' health care systems and economies. Despite the great effort put in the development of vaccines and specific treatments, no prophylaxis or effective therapeutics are currently available. Nitric oxide (NO) is a broad-spectrum antimicrobial and a potent vasodilator that has proved to be effective in reducing SARS-CoV replication and hypoxia in patients with severe acute respiratory syndrome. Given the potential of NO as treatment for SARS-CoV-2 infection, we have evaluated the in vitro antiviral effect of NO on SARS-CoV-2 replication. The NO-donor S-nitroso-N-acetylpenicillamine (SNAP) had a dose dependent inhibitory effect on SARS-CoV-2 replication, while the non S-nitrosated NAP was not active, as expected. Although the viral replication was not completely abolished (at 200 \u03bcM and 400 \u03bcM), SNAP delayed or completely prevented the development of viral cytopathic effect in treated cells, and the observed protective effect correlated with the level of inhibition of the viral replication. The capacity of the NO released from SNAP to covalently bind and inhibit SARS-CoV-2 3CL recombinant protease in vitro was also tested. The observed reduction in SARS-CoV-2 protease activity was consistent with S-nitrosation of the enzyme active site cysteine.", "doi": "10.1016/j.redox.2020.101734", "pmid": "33007504", "labels": {"Bioinformatics Support for Computational Resources": "Service", "Protein Science Facility (PSF)": "Service", "Chemical Biology Consortium Sweden": "Service", "Drug Discovery and Development": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7505071"}, {"db": "pii", "key": "S2213-2317(20)30939-3"}], "notes": [], "created": "2020-12-02T12:51:42.352Z", "modified": "2025-10-17T13:05:07.961Z"}, {"entity": "publication", "iuid": "7e253e53b3da4be5b143bc54040ae024", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7e253e53b3da4be5b143bc54040ae024.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7e253e53b3da4be5b143bc54040ae024"}}, "title": "Metagenomic analysis of bacteria in stallion semen.", "authors": [{"family": "Al-Kass", "given": "Z", "initials": "Z"}, {"family": "Guo", "given": "Y", "initials": "Y"}, {"family": "Vinnere Pettersson", "given": "O", "initials": "O", "orcid": "0000-0002-5597-1870", "researcher": {"href": "https://publications.scilifelab.se/researcher/31689f508a984d0680d285c294669615.json"}}, {"family": "Niazi", "given": "A", "initials": "A"}, {"family": "Morrell", "given": "J M", "initials": "JM", "orcid": "0000-0002-5245-7331", "researcher": {"href": "https://publications.scilifelab.se/researcher/9a9003557371478cbc972b236684ead7.json"}}], "type": "journal article", "published": "2020-10-00", "journal": {"title": "Animal Reproduction Science", "issn": "1873-2232", "volume": "221", "issue": null, "pages": "106568", "issn-l": "0378-4320"}, "abstract": "Bacteria colonize stallion semen during collection and processing which may cause disease in inseminated females or negatively affect sperm quality during storage prior to insemination. Antibiotics are added to semen extenders to control the growth of these bacteria but may induce antimicrobial resistance. Research into alternatives to antibiotics for this purpose requires knowledge of which bacteria are present in semen. Not all bacteria in semen, however, can be identified by conventional microbiological techniques. The objectives of the study were to: i) determine which bacteria are present in stallion semen using metagenomics; and ii) investigate individual differences in bacterial content in semen from all stallions on one premises. Bacterial DNA was extracted from ejaculates from seven stallions (one ejaculate per stallion) and bacteria were identified using 16S sequencing. In total, 83 bacterial genera were identified, varying from 25 to 52 among different individuals. There was a negative correlation (r = -0.81212; P < 0.05) between the presence of Treponema spp. and Advenella spp. In conclusion, most of the bacteria present in stallion semen could be identified to genus level by 16S sequencing even when present at a low frequency. This method of identification may help to clarify individual variation in bacterial content and its potential effects on fertility.", "doi": "10.1016/j.anireprosci.2020.106568", "pmid": "32861118", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S0378-4320(20)30440-1"}], "notes": [], "created": "2020-08-25T13:12:00.053Z", "modified": "2024-01-16T13:48:41.660Z"}, {"entity": "publication", "iuid": "2c61a438d2924bd587d6cc6f0e3dcefe", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2c61a438d2924bd587d6cc6f0e3dcefe.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2c61a438d2924bd587d6cc6f0e3dcefe"}}, "title": "Implications of TP53 allelic state for genome stability, clinical presentation and outcomes in myelodysplastic syndromes.", "authors": [{"family": "Bernard", "given": "Elsa", "initials": "E", "orcid": "0000-0002-2057-7187", "researcher": {"href": "https://publications.scilifelab.se/researcher/9a8cab2a7d6b4f17893dddaee1638fb4.json"}}, {"family": "Nannya", "given": "Yasuhito", "initials": "Y"}, {"family": "Hasserjian", "given": "Robert P", "initials": "RP"}, {"family": "Devlin", "given": "Sean M", "initials": "SM"}, {"family": "Tuechler", "given": "Heinz", "initials": "H", "orcid": "0000-0002-1568-3436", "researcher": {"href": "https://publications.scilifelab.se/researcher/8aeeedfebec14b7c9af34915b5320432.json"}}, {"family": "Medina-Martinez", "given": "Juan S", "initials": "JS"}, {"family": "Yoshizato", "given": "Tetsuichi", "initials": "T", "orcid": "0000-0003-4283-2983", "researcher": {"href": "https://publications.scilifelab.se/researcher/d6f499e339d2444b817a81ab2712b9e5.json"}}, {"family": "Shiozawa", "given": "Yusuke", "initials": "Y"}, {"family": "Saiki", "given": "Ryunosuke", "initials": "R"}, {"family": "Malcovati", "given": "Luca", "initials": "L"}, {"family": "Levine", "given": "Max F", "initials": "MF", "orcid": "0000-0001-5156-9086", "researcher": {"href": "https://publications.scilifelab.se/researcher/3a65c2d5e4ea4c7fa4823821a995b0ec.json"}}, {"family": "Arango", "given": "Juan E", "initials": "JE"}, {"family": "Zhou", "given": "Yangyu", "initials": "Y"}, {"family": "Sol\u00e9", "given": "Francesc", "initials": "F"}, {"family": "Cargo", "given": "Catherine A", "initials": "CA"}, {"family": "Haase", "given": "Detlef", "initials": "D"}, {"family": "Creignou", "given": "Maria", "initials": "M"}, {"family": "Germing", "given": "Ulrich", "initials": "U"}, {"family": "Zhang", "given": "Yanming", "initials": "Y"}, {"family": "Gundem", "given": "Gunes", "initials": "G"}, {"family": "Sarian", "given": "Araxe", "initials": "A"}, {"family": "van de Loosdrecht", "given": "Arjan A", "initials": "AA"}, {"family": "J\u00e4dersten", "given": "Martin", "initials": "M"}, {"family": "Tobiasson", "given": "Magnus", "initials": "M"}, {"family": "Kosmider", "given": "Olivier", "initials": "O"}, {"family": "Follo", "given": "Matilde Y", "initials": "MY", "orcid": "0000-0001-6126-0859", "researcher": {"href": "https://publications.scilifelab.se/researcher/3cbe3a0c22f7454b87bcfa2737a9a2cc.json"}}, {"family": "Thol", "given": "Felicitas", "initials": "F"}, {"family": "Pinheiro", "given": "Ronald F", "initials": "RF"}, {"family": "Santini", "given": "Valeria", "initials": "V"}, {"family": "Kotsianidis", "given": "Ioannis", "initials": "I"}, {"family": "Boultwood", "given": "Jacqueline", "initials": "J", "orcid": "0000-0002-4330-2928", "researcher": {"href": "https://publications.scilifelab.se/researcher/389b184fad7048daaa8bd0466b298374.json"}}, {"family": "Santos", "given": "Fabio P S", "initials": "FPS"}, {"family": "Schanz", "given": "Julie", "initials": "J"}, {"family": "Kasahara", "given": "Senji", "initials": "S"}, {"family": "Ishikawa", "given": "Takayuki", "initials": "T"}, {"family": "Tsurumi", "given": "Hisashi", "initials": "H"}, {"family": "Takaori-Kondo", "given": "Akifumi", "initials": "A", "orcid": "0000-0001-7678-4284", "researcher": {"href": "https://publications.scilifelab.se/researcher/580e4d306fca4abeb09cea24b9fb381e.json"}}, {"family": "Kiguchi", "given": "Toru", "initials": "T"}, {"family": "Polprasert", "given": "Chantana", "initials": "C"}, {"family": "Bennett", "given": "John M", "initials": "JM"}, {"family": "Klimek", "given": "Virginia M", "initials": "VM"}, {"family": "Savona", "given": "Michael R", "initials": "MR", "orcid": "0000-0003-3763-5504", "researcher": {"href": "https://publications.scilifelab.se/researcher/50a3df7d0cee4ad484ba249dc87de866.json"}}, {"family": "Belickova", "given": "Monika", "initials": "M", "orcid": "0000-0002-9158-881X", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ff36ac18c71412b94d17252c44e70bd.json"}}, {"family": "Ganster", "given": "Christina", "initials": "C", "orcid": "0000-0002-7566-5985", "researcher": {"href": "https://publications.scilifelab.se/researcher/572629d9ced648fab310107d492fec38.json"}}, {"family": "Palomo", "given": "Laura", "initials": "L"}, {"family": "Sanz", "given": "Guillermo", "initials": "G", "orcid": "0000-0002-2767-8191", "researcher": {"href": "https://publications.scilifelab.se/researcher/df83862e8b6d43d7ae2707e28420218f.json"}}, {"family": "Ades", "given": "Lionel", "initials": "L"}, {"family": "Della Porta", "given": "Matteo Giovanni", "initials": "MG"}, {"family": "Elias", "given": "Harold K", "initials": "HK"}, {"family": "Smith", "given": "Alexandra G", "initials": "AG"}, {"family": "Werner", "given": "Yesenia", "initials": "Y"}, {"family": "Patel", "given": "Minal", "initials": "M"}, {"family": "Viale", "given": "Agn\u00e8s", "initials": "A"}, {"family": "Vanness", "given": "Katelynd", "initials": "K"}, {"family": "Neuberg", "given": "Donna S", "initials": "DS", "orcid": "0000-0003-2566-3145", "researcher": {"href": "https://publications.scilifelab.se/researcher/e2f9cbb622f040bebdfcb68657035be1.json"}}, {"family": "Stevenson", "given": "Kristen E", "initials": "KE"}, {"family": "Menghrajani", "given": "Kamal", "initials": "K"}, {"family": "Bolton", "given": "Kelly L", "initials": "KL"}, {"family": "Fenaux", "given": "Pierre", "initials": "P"}, {"family": "Pellagatti", "given": "Andrea", "initials": "A"}, {"family": "Platzbecker", "given": "Uwe", "initials": "U"}, {"family": "Heuser", "given": "Michael", "initials": "M", "orcid": "0000-0001-5318-9044", "researcher": {"href": "https://publications.scilifelab.se/researcher/fb00432d76f74293a5acdbc17a3f2305.json"}}, {"family": "Valent", "given": "Peter", "initials": "P"}, {"family": "Chiba", "given": "Shigeru", "initials": "S"}, {"family": "Miyazaki", "given": "Yasushi", "initials": "Y"}, {"family": "Finelli", "given": "Carlo", "initials": "C"}, {"family": "Voso", "given": "Maria Teresa", "initials": "MT", "orcid": "0000-0002-6164-4761", "researcher": {"href": "https://publications.scilifelab.se/researcher/54c19342a17e44249d7b4e4ae05d3e7a.json"}}, {"family": "Shih", "given": "Lee-Yung", "initials": "LY"}, {"family": "Fontenay", "given": "Michaela", "initials": "M", "orcid": "0000-0002-5492-6349", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a304a24a07e4f66b50eb9b3204d7eb4.json"}}, {"family": "Jansen", "given": "Joop H", "initials": "JH"}, {"family": "Cervera", "given": "Jos\u00e9", "initials": "J"}, {"family": "Atsuta", "given": "Yoshiko", "initials": "Y"}, {"family": "Gattermann", "given": "Norbert", "initials": "N"}, {"family": "Ebert", "given": "Benjamin L", "initials": "BL", "orcid": "0000-0003-0197-5451", "researcher": {"href": "https://publications.scilifelab.se/researcher/eeb0be1eb2be4bb48ec7f9dc17bd696f.json"}}, {"family": "Bejar", "given": "Rafael", "initials": "R", "orcid": "0000-0002-5603-4598", "researcher": {"href": "https://publications.scilifelab.se/researcher/33fcd878bc6e48e98950a35a0cebdbbb.json"}}, {"family": "Greenberg", "given": "Peter L", "initials": "PL"}, {"family": "Cazzola", "given": "Mario", "initials": "M", "orcid": "0000-0001-6984-8817", "researcher": {"href": "https://publications.scilifelab.se/researcher/e85ab5f89c604aad824a42107184f196.json"}}, {"family": "Hellstr\u00f6m-Lindberg", "given": "Eva", "initials": "E"}, {"family": "Ogawa", "given": "Seishi", "initials": "S", "orcid": "0000-0002-7778-5374", "researcher": {"href": "https://publications.scilifelab.se/researcher/fbcc3b1b5f3045a7acd123222445449d.json"}}, {"family": "Papaemmanuil", "given": "Elli", "initials": "E", "orcid": "0000-0003-1709-8983", "researcher": {"href": "https://publications.scilifelab.se/researcher/2f67e7f1297e472c8f31639c02d28905.json"}}], "type": "journal article", "published": "2020-10-00", "journal": {"title": "Nat. Med.", "issn": "1546-170X", "volume": "26", "issue": "10", "pages": "1549-1556", "issn-l": "1078-8956"}, "abstract": "Tumor protein p53 (TP53) is the most frequently mutated gene in cancer1,2. In patients with myelodysplastic syndromes (MDS), TP53 mutations are associated with high-risk disease3,4, rapid transformation to acute myeloid leukemia (AML)5, resistance to conventional therapies6-8 and dismal outcomes9. Consistent with the tumor-suppressive role of TP53, patients harbor both mono- and biallelic mutations10. However, the biological and clinical implications of TP53 allelic state have not been fully investigated in MDS or any other cancer type. We analyzed 3,324 patients with MDS for TP53 mutations and allelic imbalances and delineated two subsets of patients with distinct phenotypes and outcomes. One-third of TP53-mutated patients had monoallelic mutations whereas two-thirds had multiple hits (multi-hit) consistent with biallelic targeting. Established associations with complex karyotype, few co-occurring mutations, high-risk presentation and poor outcomes were specific to multi-hit patients only. TP53 multi-hit state predicted risk of death and leukemic transformation independently of the Revised International Prognostic Scoring System (IPSS-R)11. Surprisingly, monoallelic patients did not differ from TP53 wild-type patients in outcomes and response to therapy. This study shows that consideration of TP53 allelic state is critical for diagnostic and prognostic precision in MDS as well as in future correlative studies of treatment response.", "doi": "10.1038/s41591-020-1008-z", "pmid": "32747829", "labels": {"Clinical Genomics Uppsala": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41591-020-1008-z"}, {"db": "pmc", "key": "PMC8381722"}, {"db": "mid", "key": "NIHMS1715889"}], "notes": [], "created": "2020-12-10T14:46:50.666Z", "modified": "2021-11-10T12:46:47.582Z"}, {"entity": "publication", "iuid": "b8a2612630214776a9f44ac10c70474a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b8a2612630214776a9f44ac10c70474a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b8a2612630214776a9f44ac10c70474a"}}, "title": "Geographically widespread invasive meningococcal disease caused by a ciprofloxacin resistant non-groupable strain of the ST-175 clonal complex.", "authors": [{"family": "Willerton", "given": "Laura", "initials": "L"}, {"family": "Lucidarme", "given": "Jay", "initials": "J"}, {"family": "Campbell", "given": "Helen", "initials": "H"}, {"family": "Caugant", "given": "Dominique A", "initials": "DA"}, {"family": "Claus", "given": "Heike", "initials": "H"}, {"family": "Jacobsson", "given": "Susanne", "initials": "S"}, {"family": "Ladhani", "given": "Shamez N", "initials": "SN"}, {"family": "M\u00f6lling", "given": "Paula", "initials": "P"}, {"family": "Neri", "given": "Arianna", "initials": "A"}, {"family": "Stefanelli", "given": "Paola", "initials": "P"}, {"family": "Taha", "given": "Muhamed-Kheir", "initials": "M"}, {"family": "Vogel", "given": "Ulrich", "initials": "U"}, {"family": "Borrow", "given": "Ray", "initials": "R"}], "type": "journal article", "published": "2020-10-00", "journal": {"title": "J Infect", "issn": "1532-2742", "issn-l": null, "volume": "81", "issue": "4", "pages": "575-584"}, "abstract": "Invasive meningococcal disease (IMD) caused by non-serogroupable (NG) strains mainly affects immunocompromised individuals. Reduced susceptibility to penicillin in meningococci is increasing in Europe but ciprofloxacin resistance remains rare. In 2019, three travel-related meningococcal disease cases caused by a ciprofloxacin-resistant NG strain were identified in England, leading Germany to report four additional IMD cases (2016 to 2019). We describe these and newly identified cases and characterise the strain responsible.\r\n\r\nCases were identified as part of national surveillance and by analysing available genomes using PubMLST tools.\r\n\r\nOf the cases identified in England in 2019, two geographically distinct cases developed conjunctivitis after returning from Mecca (Kingdom of Saudi Arabia) and a third linked case presented with IMD. Of the four cases from Germany, three occurred in asylum seekers - two familial and a further geographically distinct case. Further IMD cases were identified in Italy (n = 2; 2017-2018), Sweden (n = 1; 2016) and England (n = 1; 2015). A single ST-175 clonal complex (cc175) strain with genosubtype P1.22-11,15-25 was responsible. Decreased susceptibility to penicillin was widespread with three ciprofloxacin resistant subclusters. Constituent isolates were potentially covered by subcapsular vaccines.\r\n\r\nThis disease associated NG cc175 strain exhibits resistance to antibiotics commonly used to prevent IMD but is potentially covered by subcapsular (meningococcal B) vaccines.", "doi": "10.1016/j.jinf.2020.08.030", "pmid": "32858070", "labels": {"Clinical Genomics \u00d6rebro": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0163-4453(20)30570-3"}], "notes": [], "created": "2020-11-27T13:58:06.441Z", "modified": "2021-12-08T12:30:28.063Z"}, {"entity": "publication", "iuid": "cbca211bcfb64e4f9988962d8cef7fdb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cbca211bcfb64e4f9988962d8cef7fdb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cbca211bcfb64e4f9988962d8cef7fdb"}}, "title": "Genomic and drug target evaluation of 90 cardiovascular proteins in 30,931 individuals.", "authors": [{"family": "Folkersen", "given": "Lasse", "initials": "L", "orcid": "0000-0003-0708-9530", "researcher": {"href": "https://publications.scilifelab.se/researcher/7202a83ff6484d5c9d77f448f93c6520.json"}}, {"family": "Gustafsson", "given": "Stefan", "initials": "S"}, {"family": "Wang", "given": "Qin", "initials": "Q"}, {"family": "Hansen", "given": "Daniel Hvidberg", "initials": "DH", "orcid": "0000-0003-3285-605X", "researcher": {"href": "https://publications.scilifelab.se/researcher/c74393b778ad4c989c6f6f2290eb5f94.json"}}, {"family": "Hedman", "given": "\u00c5sa K", "initials": "\u00c5K"}, {"family": "Schork", "given": "Andrew", "initials": "A"}, {"family": "Page", "given": "Karen", "initials": "K"}, {"family": "Zhernakova", "given": "Daria V", "initials": "DV"}, {"family": "Wu", "given": "Yang", "initials": "Y", "orcid": "0000-0002-0128-7280", "researcher": {"href": "https://publications.scilifelab.se/researcher/5c005cb8ac0a40c38b07b26fc3184354.json"}}, {"family": "Peters", "given": "James", "initials": "J"}, {"family": "Eriksson", "given": "Niclas", "initials": "N", "orcid": "0000-0002-2152-4343", "researcher": {"href": "https://publications.scilifelab.se/researcher/64611a83caba46d597f45371b77de26b.json"}}, {"family": "Bergen", "given": "Sarah E", "initials": "SE"}, {"family": "Boutin", "given": "Thibaud S", "initials": "TS"}, {"family": "Bretherick", "given": "Andrew D", "initials": "AD", "orcid": "0000-0001-9258-3140", "researcher": {"href": "https://publications.scilifelab.se/researcher/177c5c98460c44a79ff1f07c5df05b55.json"}}, {"family": "Enroth", "given": "Stefan", "initials": "S", "orcid": "0000-0002-5056-9137", "researcher": {"href": "https://publications.scilifelab.se/researcher/16bb97ef16ee49f3ae0c7ea0495fd971.json"}}, {"family": "Kalnapenkis", "given": "Anette", "initials": "A"}, {"family": "G\u00e5din", "given": "Jesper R", "initials": "JR"}, {"family": "Suur", "given": "Bianca E", "initials": "BE"}, {"family": "Chen", "given": "Yan", "initials": "Y"}, {"family": "Matic", "given": "Ljubica", "initials": "L"}, {"family": "Gale", "given": "Jeremy D", "initials": "JD"}, {"family": "Lee", "given": "Julie", "initials": "J", "orcid": "0000-0001-6090-6718", "researcher": {"href": "https://publications.scilifelab.se/researcher/724fc189ac8d4764a924f07fe7806058.json"}}, {"family": "Zhang", "given": "Weidong", "initials": "W"}, {"family": "Quazi", "given": "Amira", "initials": "A"}, {"family": "Ala-Korpela", "given": "Mika", "initials": "M", "orcid": "0000-0001-5905-1206", "researcher": {"href": "https://publications.scilifelab.se/researcher/9a1d51911c554533b4f458993efd95e7.json"}}, {"family": "Choi", "given": "Seung Hoan", "initials": "SH"}, {"family": "Claringbould", "given": "Annique", "initials": "A", "orcid": "0000-0002-9201-6557", "researcher": {"href": "https://publications.scilifelab.se/researcher/f273594a78dd47b88de6322bfae64900.json"}}, {"family": "Danesh", "given": "John", "initials": "J"}, {"family": "Davey Smith", "given": "George", "initials": "G", "orcid": "0000-0002-1407-8314", "researcher": {"href": "https://publications.scilifelab.se/researcher/0790d5850377432087ad3900af0044e0.json"}}, {"family": "de Masi", "given": "Federico", "initials": "F"}, {"family": "Elmst\u00e5hl", "given": "S\u00f6lve", "initials": "S"}, {"family": "Engstr\u00f6m", "given": "Gunnar", "initials": "G"}, {"family": "Fauman", "given": "Eric", "initials": "E", "orcid": "0000-0002-9739-0249", "researcher": {"href": "https://publications.scilifelab.se/researcher/33640d6d585f4715ad0754af256954fd.json"}}, {"family": "Fernandez", "given": "Celine", "initials": "C", "orcid": "0000-0003-1290-4982", "researcher": {"href": "https://publications.scilifelab.se/researcher/0403fdacd924464a913261e53f6e6083.json"}}, {"family": "Franke", "given": "Lude", "initials": "L", "orcid": "0000-0002-5159-8802", "researcher": {"href": "https://publications.scilifelab.se/researcher/ee63161f78274a53b615c05555b81a10.json"}}, {"family": "Franks", "given": "Paul W", "initials": "PW", "orcid": "0000-0002-0520-7604", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ebbf40c0f7e49dd8c75a2b6cbf27276.json"}}, {"family": "Giedraitis", "given": "Vilmantas", "initials": "V", "orcid": "0000-0003-3423-2021", "researcher": {"href": "https://publications.scilifelab.se/researcher/7c95879213664e00b66aeee2e8ece975.json"}}, {"family": "Haley", "given": "Chris", "initials": "C", "orcid": "0000-0002-9811-0210", "researcher": {"href": "https://publications.scilifelab.se/researcher/c4fee769cfe84186abbc285881e0529c.json"}}, {"family": "Hamsten", "given": "Anders", "initials": "A"}, {"family": "Ingason", "given": "Andres", "initials": "A"}, {"family": "Johansson", "given": "\u00c5sa", "initials": "\u00c5", "orcid": "0000-0002-2915-4498", "researcher": {"href": "https://publications.scilifelab.se/researcher/76265c54961046e99bdb0439f9ae1d34.json"}}, {"family": "Joshi", "given": "Peter K", "initials": "PK"}, {"family": "Lind", "given": "Lars", "initials": "L"}, {"family": "Lindgren", "given": "Cecilia M", "initials": "CM"}, {"family": "Lubitz", "given": "Steven", "initials": "S", "orcid": "0000-0002-9599-4866", "researcher": {"href": "https://publications.scilifelab.se/researcher/25bb007311104c92983dbcce80f72260.json"}}, {"family": "Palmer", "given": "Tom", "initials": "T", "orcid": "0000-0003-4655-4511", "researcher": {"href": "https://publications.scilifelab.se/researcher/7f71dc0736834c72a59b9b14f1ae471a.json"}}, {"family": "Macdonald-Dunlop", "given": "Erin", "initials": "E", "orcid": "0000-0001-6569-6086", "researcher": {"href": "https://publications.scilifelab.se/researcher/af015c7cf68b470cbca81fe7fa1b58c4.json"}}, {"family": "Magnusson", "given": "Martin", "initials": "M", "orcid": "0000-0003-1710-5936", "researcher": {"href": "https://publications.scilifelab.se/researcher/6126a96481bb4c398a6e8ab6fa596b28.json"}}, {"family": "Melander", "given": "Olle", "initials": "O"}, {"family": "Michaelsson", "given": "Karl", "initials": "K", "orcid": "0000-0003-2815-1217", "researcher": {"href": "https://publications.scilifelab.se/researcher/eff63868e95240f695d47e871e31947f.json"}}, {"family": "Morris", "given": "Andrew P", "initials": "AP"}, {"family": "M\u00e4gi", "given": "Reedik", "initials": "R"}, {"family": "Nagle", "given": "Michael W", "initials": "MW", "orcid": "0000-0002-4677-7582", "researcher": {"href": "https://publications.scilifelab.se/researcher/5da07a509b1740648199997ee5ea73a3.json"}}, {"family": "Nilsson", "given": "Peter M", "initials": "PM", "orcid": "0000-0002-5652-8459", "researcher": {"href": "https://publications.scilifelab.se/researcher/f23c2a10ac2a4d73a8f62b94855635f1.json"}}, {"family": "Nilsson", "given": "Jan", "initials": "J", "orcid": "0000-0002-9752-7479", "researcher": {"href": "https://publications.scilifelab.se/researcher/8777140448bc47f0a7984db3c15c0e23.json"}}, {"family": "Orho-Melander", "given": "Marju", "initials": "M"}, {"family": "Polasek", "given": "Ozren", "initials": "O"}, {"family": "Prins", "given": "Bram", "initials": "B", "orcid": "0000-0001-5774-034X", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd911c5f0da149afb2b4184892ed4b71.json"}}, {"family": "P\u00e5lsson", "given": "Erik", "initials": "E"}, {"family": "Qi", "given": "Ting", "initials": "T"}, {"family": "Sj\u00f6gren", "given": "Marketa", "initials": "M"}, {"family": "Sundstr\u00f6m", "given": "Johan", "initials": "J", "orcid": "0000-0003-2247-8454", "researcher": {"href": "https://publications.scilifelab.se/researcher/91a40d3c138d43f2b0d38f66be4b71c7.json"}}, {"family": "Surendran", "given": "Praveen", "initials": "P"}, {"family": "V\u00f5sa", "given": "Urmo", "initials": "U"}, {"family": "Werge", "given": "Thomas", "initials": "T", "orcid": "0000-0003-1829-0766", "researcher": {"href": "https://publications.scilifelab.se/researcher/89e727c9b54c4e23b9104fbc10b7b4e3.json"}}, {"family": "Wernersson", "given": "Rasmus", "initials": "R"}, {"family": "Westra", "given": "Harm-Jan", "initials": "H"}, {"family": "Yang", "given": "Jian", "initials": "J"}, {"family": "Zhernakova", "given": "Alexandra", "initials": "A"}, {"family": "\u00c4rnl\u00f6v", "given": "Johan", "initials": "J"}, {"family": "Fu", "given": "Jingyuan", "initials": "J", "orcid": "0000-0001-5578-1236", "researcher": {"href": "https://publications.scilifelab.se/researcher/e55de478e461486087cec6a8d073666f.json"}}, {"family": "Smith", "given": "J Gustav", "initials": "JG"}, {"family": "Esko", "given": "T\u00f5nu", "initials": "T", "orcid": "0000-0003-1982-6569", "researcher": {"href": "https://publications.scilifelab.se/researcher/d72619c1e29d44e8b8454902d2af8d9e.json"}}, {"family": "Hayward", "given": "Caroline", "initials": "C", "orcid": "0000-0002-9405-9550", "researcher": {"href": "https://publications.scilifelab.se/researcher/cd49e9ad5a024c7ca2f1aa97d9e58eba.json"}}, {"family": "Gyllensten", "given": "Ulf", "initials": "U"}, {"family": "Landen", "given": "Mikael", "initials": "M", "orcid": "0000-0002-4496-6451", "researcher": {"href": "https://publications.scilifelab.se/researcher/792e2b8b8da94572a4d2815703d29749.json"}}, {"family": "Siegbahn", "given": "Agneta", "initials": "A"}, {"family": "Wilson", "given": "James F", "initials": "JF"}, {"family": "Wallentin", "given": "Lars", "initials": "L"}, {"family": "Butterworth", "given": "Adam S", "initials": "AS", "orcid": "0000-0002-6915-9015", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b8c140c80d942c4b1b684876e4d6180.json"}}, {"family": "Holmes", "given": "Michael V", "initials": "MV", "orcid": "0000-0001-6617-0879", "researcher": {"href": "https://publications.scilifelab.se/researcher/2fc91d91672d47fa9759a2af3e3f1f3a.json"}}, {"family": "Ingelsson", "given": "Erik", "initials": "E", "orcid": "0000-0003-2256-6972", "researcher": {"href": "https://publications.scilifelab.se/researcher/689bc741ea6547d18de7080c84d0193e.json"}}, {"family": "M\u00e4larstig", "given": "Anders", "initials": "A", "orcid": "0000-0003-2608-1358", "researcher": {"href": "https://publications.scilifelab.se/researcher/e70c845d32264b448e0b4631b826be6d.json"}}], "type": "journal article", "published": "2020-10-00", "journal": {"title": "Nat Metab", "issn": "2522-5812", "issn-l": "2522-5812", "volume": "2", "issue": "10", "pages": "1135-1148"}, "abstract": "Circulating proteins are vital in human health and disease and are frequently used as biomarkers for clinical decision-making or as targets for pharmacological intervention. Here, we map and replicate protein quantitative trait loci (pQTL) for 90 cardiovascular proteins in over 30,000 individuals, resulting in 451 pQTLs for 85 proteins. For each protein, we further perform pathway mapping to obtain trans-pQTL gene and regulatory designations. We substantiate these regulatory findings with orthogonal evidence for trans-pQTLs using mouse knockdown experiments (ABCA1 and TRIB1) and clinical trial results (chemokine receptors CCR2 and CCR5), with consistent regulation. Finally, we evaluate known drug targets, and suggest new target candidates or repositioning opportunities using Mendelian randomization. This identifies 11 proteins with causal evidence of involvement in human disease that have not previously been targeted, including EGF, IL-16, PAPPA, SPON1, F3, ADM, CASP-8, CHI3L1, CXCL16, GDF15 and MMP-12. Taken together, these findings demonstrate the utility of large-scale mapping of the genetics of the proteome and provide a resource for future precision studies of circulating proteins in human health.", "doi": "10.1038/s42255-020-00287-2", "pmid": "33067605", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "Affinity Proteomics Uppsala": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s42255-020-00287-2"}, {"db": "pmc", "key": "PMC7611474"}, {"db": "mid", "key": "EMS131454"}], "notes": [], "created": "2020-10-20T06:59:28.770Z", "modified": "2024-11-27T16:17:54.447Z"}, {"entity": "publication", "iuid": "d71873c329c7421db086762eddcf7cb7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d71873c329c7421db086762eddcf7cb7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d71873c329c7421db086762eddcf7cb7"}}, "title": "GPSeq reveals the radial organization of chromatin in the cell nucleus.", "authors": [{"family": "Girelli", "given": "Gabriele", "initials": "G", "orcid": "0000-0003-4264-6494", "researcher": {"href": "https://publications.scilifelab.se/researcher/a607510e88954d0980e1d4505ab27ee7.json"}}, {"family": "Custodio", "given": "Joaquin", "initials": "J"}, {"family": "Kallas", "given": "Tomasz", "initials": "T"}, {"family": "Agostini", "given": "Federico", "initials": "F", "orcid": "0000-0002-5453-2737", "researcher": {"href": "https://publications.scilifelab.se/researcher/a21ea8b7e9a5427eb0e48a822c840b8b.json"}}, {"family": "Wernersson", "given": "Erik", "initials": "E", "orcid": "0000-0003-4778-1660", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae0de6d4af244cec84bbe8c1240d89ae.json"}}, {"family": "Spanjaard", "given": "Bastiaan", "initials": "B"}, {"family": "Mota", "given": "Ana", "initials": "A"}, {"family": "Kolbeinsdottir", "given": "Solrun", "initials": "S"}, {"family": "Gelali", "given": "Eleni", "initials": "E", "orcid": "0000-0003-0067-5473", "researcher": {"href": "https://publications.scilifelab.se/researcher/b1a4d90932dd45509d71a672ec5a12af.json"}}, {"family": "Crosetto", "given": "Nicola", "initials": "N", "orcid": "0000-0002-3019-6978", "researcher": {"href": "https://publications.scilifelab.se/researcher/bb66f0013e954d99a2be4df7309b7ae3.json"}}, {"family": "Bienko", "given": "Magda", "initials": "M", "orcid": "0000-0002-6499-9082", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a983bc4595448be8b0f7487f17afa7d.json"}}], "type": "journal article", "published": "2020-10-00", "journal": {"title": "Nat. Biotechnol.", "issn": "1546-1696", "volume": "38", "issue": "10", "pages": "1184-1193", "issn-l": "1087-0156"}, "abstract": "With the exception of lamina-associated domains, the radial organization of chromatin in mammalian cells remains largely unexplored. Here we describe genomic loci positioning by sequencing (GPSeq), a genome-wide method for inferring distances to the nuclear lamina all along the nuclear radius. GPSeq relies on gradual restriction digestion of chromatin from the nuclear lamina toward the nucleus center, followed by sequencing of the generated cut sites. Using GPSeq, we mapped the radial organization of the human genome at 100-kb resolution, which revealed radial patterns of genomic and epigenomic features and gene expression, as well as A and B subcompartments. By combining radial information with chromosome contact frequencies measured by Hi-C, we substantially improved the accuracy of whole-genome structure modeling. Finally, we charted the radial topography of DNA double-strand breaks, germline variants and cancer mutations and found that they have distinctive radial arrangements in A and B subcompartments. We conclude that GPSeq can reveal fundamental aspects of genome architecture.", "doi": "10.1038/s41587-020-0519-y", "pmid": "32451505", "labels": {"Integrated Microscopy Technologies Stockholm": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41587-020-0519-y"}, {"db": "pmc", "key": "PMC7610410"}, {"db": "mid", "key": "EMS118404"}], "notes": [], "created": "2020-05-26T07:12:39.312Z", "modified": "2021-11-10T12:46:51.496Z"}, {"entity": "publication", "iuid": "7a14c5167e074030981441eb5dcefaad", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7a14c5167e074030981441eb5dcefaad.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7a14c5167e074030981441eb5dcefaad"}}, "title": "Function of multiple sclerosis-protective HLA class I alleles revealed by genome-wide protein-quantitative trait loci mapping of interferon signalling.", "authors": [{"family": "Lundtoft", "given": "Christian", "initials": "C", "orcid": "0000-0001-5872-4253", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a05532d3aad4e2dbe00a4724e8dddd8.json"}}, {"family": "Pucholt", "given": "Pascal", "initials": "P", "orcid": "0000-0003-3342-1373", "researcher": {"href": "https://publications.scilifelab.se/researcher/61a214ff2d494b568cb6da944e858acf.json"}}, {"family": "Imgenberg-Kreuz", "given": "Juliana", "initials": "J", "orcid": "0000-0002-7230-8990", "researcher": {"href": "https://publications.scilifelab.se/researcher/5d4c2f630d484ee780c2c12aaabdb939.json"}}, {"family": "Carlsson-Alml\u00f6f", "given": "Jonas", "initials": "J", "orcid": "0000-0002-1211-9821", "researcher": {"href": "https://publications.scilifelab.se/researcher/046904cd12eb4764bd2dcadc876f65d7.json"}}, {"family": "Eloranta", "given": "Maija-Leena", "initials": "ML", "orcid": "0000-0002-8454-1351", "researcher": {"href": "https://publications.scilifelab.se/researcher/d162e060954d420e825884f254886dcd.json"}}, {"family": "Syv\u00e4nen", "given": "Ann-Christine", "initials": "AC", "orcid": "0000-0002-9681-9146", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7012e35025543379380cb90efd71243.json"}}, {"family": "Nordmark", "given": "Gunnel", "initials": "G", "orcid": "0000-0002-3829-7431", "researcher": {"href": "https://publications.scilifelab.se/researcher/188fda53498740dbb007441cc94bb1ad.json"}}, {"family": "Sandling", "given": "Johanna K", "initials": "JK", "orcid": "0000-0003-1382-2321", "researcher": {"href": "https://publications.scilifelab.se/researcher/9c7bae5a05ac47eeac96547ca7336767.json"}}, {"family": "Kockum", "given": "Ingrid", "initials": "I", "orcid": "0000-0002-0867-4726", "researcher": {"href": "https://publications.scilifelab.se/researcher/03ebcc6a01ef4d0db4e4673aff8de5d8.json"}}, {"family": "Olsson", "given": "Tomas", "initials": "T", "orcid": "0000-0002-2938-1877", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd9a20a941214f97a22f010df37cd8e1.json"}}, {"family": "R\u00f6nnblom", "given": "Lars", "initials": "L", "orcid": "0000-0001-9403-6503", "researcher": {"href": "https://publications.scilifelab.se/researcher/053ed3b657124a1bab3a78dc685556e6.json"}}, {"family": "Hagberg", "given": "Niklas", "initials": "N", "orcid": "0000-0003-2064-2716", "researcher": {"href": "https://publications.scilifelab.se/researcher/0d0998bb419c424083b0978ebdbe8629.json"}}], "type": "journal article", "published": "2020-10-00", "journal": {"title": "PLoS Genet.", "issn": "1553-7404", "volume": "16", "issue": "10", "pages": "e1009199", "issn-l": "1553-7390"}, "abstract": "Interferons (IFNs) are cytokines that are central to the host defence against viruses and other microorganisms. If not properly regulated, IFNs may contribute to the pathogenesis of inflammatory autoimmune, or infectious diseases. To identify genetic polymorphisms regulating the IFN system we performed an unbiased genome-wide protein-quantitative trait loci (pQTL) mapping of cell-type specific type I and type II IFN receptor levels and their responses in immune cells from 303 healthy individuals. Seven genome-wide significant (p < 5.0E-8) pQTLs were identified. Two independent SNPs that tagged the multiple sclerosis (MS)-protective HLA class I alleles A*02/A*68 and B*44, respectively, were associated with increased levels of IFNAR2 in B and T cells, with the most prominent effect in IgD-CD27+ memory B cells. The increased IFNAR2 levels in B cells were replicated in cells from an independent set of healthy individuals and in MS patients. Despite increased IFNAR2 levels, B and T cells carrying the MS-protective alleles displayed a reduced response to type I IFN stimulation. Expression and methylation-QTL analysis demonstrated increased mRNA expression of the pseudogene HLA-J in B cells carrying the MS-protective class I alleles, possibly driven via methylation-dependent transcriptional regulation. Together these data suggest that the MS-protective effects of HLA class I alleles are unrelated to their antigen-presenting function, and propose a previously unappreciated function of type I IFN signalling in B and T cells in MS immune-pathogenesis.", "doi": "10.1371/journal.pgen.1009199", "pmid": "33104735", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "PGENETICS-D-20-01001"}, {"db": "pmc", "key": "PMC7644105"}], "notes": [], "created": "2020-11-05T14:07:48.822Z", "modified": "2024-01-16T13:48:41.667Z"}, {"entity": "publication", "iuid": "f14cba2314b74cebb473dab317adef9d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f14cba2314b74cebb473dab317adef9d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f14cba2314b74cebb473dab317adef9d"}}, "title": "Exploring the bacterial nano-universe.", "authors": [{"family": "S\u00f6derholm", "given": "Niklas", "initials": "N", "orcid": "0000-0003-3964-3751", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff74d1308e044d7f81ddbe1eb73cfd9c.json"}}, {"family": "Singh", "given": "Birendra", "initials": "B", "orcid": "0000-0002-7246-1442", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a37eae28b0b45678502b7be34dbae99.json"}}, {"family": "Uhlin", "given": "Bernt Eric", "initials": "BE", "orcid": "0000-0002-2991-8072", "researcher": {"href": "https://publications.scilifelab.se/researcher/9faa19d33fd84728bb6df987ba16475f.json"}}, {"family": "Sandblad", "given": "Linda", "initials": "L", "orcid": "0000-0003-3492-3287", "researcher": {"href": "https://publications.scilifelab.se/researcher/070825e0190a4e9a932e79663d2bc89f.json"}}], "type": "journal article", "published": "2020-10-00", "journal": {"title": "Curr. Opin. Struct. Biol.", "issn": "1879-033X", "volume": "64", "issue": null, "pages": "166-173", "issn-l": "0959-440X"}, "abstract": "Since the days of the first acknowledged microscopist, Antonie van Leeuwenhoek, the 'animalcules', that is, bacteria and other microbes have been subject to increasingly detailed visualization. With the currently most sophisticated molecular imaging method; cryo electron tomography (Cryo-ET), we are reaching the milestone of being able to image an entire organism in a single dataset at nanometer resolution. Cryo-ET will enable the next revolution in our understanding of bacterial cells, their ultra-structure and intricate molecular nanomachines. Here, we highlight recent research discoveries based on constantly progressing technology developments. We discuss advantages and challenges of using Cryo-ET to visualize spatial structure of microorganisms and macromolecular complexes in their native environment.", "doi": "10.1016/j.sbi.2020.07.002", "pmid": "32846309", "labels": {"Cryo-EM": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0959-440X(20)30125-1"}], "notes": [], "created": "2020-12-10T11:09:02.691Z", "modified": "2021-11-10T12:46:53.752Z"}, {"entity": "publication", "iuid": "623e835b9c244de089f8d19ef8441b5b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/623e835b9c244de089f8d19ef8441b5b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/623e835b9c244de089f8d19ef8441b5b"}}, "title": "Differences in structure and hibernation mechanism highlight diversification of the microsporidian ribosome.", "authors": [{"family": "Ehrenbolger", "given": "Kai", "initials": "K", "orcid": "0000-0003-1312-5825", "researcher": {"href": "https://publications.scilifelab.se/researcher/3acfe2f8d3914170a9eb6515a0c7976c.json"}}, {"family": "Jespersen", "given": "Nathan", "initials": "N", "orcid": "0000-0001-6931-1526", "researcher": {"href": "https://publications.scilifelab.se/researcher/8be9dc8984bb4fec9f6406bd20477258.json"}}, {"family": "Sharma", "given": "Himanshu", "initials": "H"}, {"family": "Sokolova", "given": "Yuliya Y", "initials": "YY", "orcid": "0000-0003-0448-7226", "researcher": {"href": "https://publications.scilifelab.se/researcher/19c096a5c1324f86a7860964f8db3672.json"}}, {"family": "Tokarev", "given": "Yuri S", "initials": "YS", "orcid": "0000-0003-0524-0778", "researcher": {"href": "https://publications.scilifelab.se/researcher/5b692a92842345e497b30efabd876731.json"}}, {"family": "Vossbrinck", "given": "Charles R", "initials": "CR"}, {"family": "Barandun", "given": "Jonas", "initials": "J", "orcid": "0000-0003-2971-8190", "researcher": {"href": "https://publications.scilifelab.se/researcher/2456fbe0b6bf406889842ab9f0267c22.json"}}], "type": "journal article", "published": "2020-10-00", "journal": {"title": "PLoS Biol.", "issn": "1545-7885", "volume": "18", "issue": "10", "pages": "e3000958", "issn-l": "1544-9173"}, "abstract": "Assembling and powering ribosomes are energy-intensive processes requiring fine-tuned cellular control mechanisms. In organisms operating under strict nutrient limitations, such as pathogenic microsporidia, conservation of energy via ribosomal hibernation and recycling is critical. The mechanisms by which hibernation is achieved in microsporidia, however, remain poorly understood. Here, we present the cryo-electron microscopy structure of the ribosome from Paranosema locustae spores, bound by the conserved eukaryotic hibernation and recycling factor Lso2. The microsporidian Lso2 homolog adopts a V-shaped conformation to bridge the mRNA decoding site and the large subunit tRNA binding sites, providing a reversible ribosome inactivation mechanism. Although microsporidian ribosomes are highly compacted, the P. locustae ribosome retains several rRNA segments absent in other microsporidia, and represents an intermediate state of rRNA reduction. In one case, the near complete reduction of an expansion segment has resulted in a single bound nucleotide, which may act as an architectural co-factor to stabilize a protein-protein interface. The presented structure highlights the reductive evolution in these emerging pathogens and sheds light on a conserved mechanism for eukaryotic ribosome hibernation.", "doi": "10.1371/journal.pbio.3000958", "pmid": "33125369", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pii", "key": "PBIOLOGY-D-20-02271"}, {"db": "pmc", "key": "PMC7644102"}], "notes": [], "created": "2020-12-10T11:20:47.792Z", "modified": "2021-11-10T12:46:54.921Z"}, {"entity": "publication", "iuid": "08a45a5b61b8441ea51d9b53a518fc25", "links": {"self": {"href": "https://publications.scilifelab.se/publication/08a45a5b61b8441ea51d9b53a518fc25.json"}, "display": {"href": "https://publications.scilifelab.se/publication/08a45a5b61b8441ea51d9b53a518fc25"}}, "title": "Development of a chemical probe against NUDT15.", "authors": [{"family": "Zhang", "given": "Si Min", "initials": "SM", "orcid": "0000-0001-7763-603X", "researcher": {"href": "https://publications.scilifelab.se/researcher/1eac01c3a53d4940ade49b24f13dd214.json"}}, {"family": "Desroses", "given": "Matthieu", "initials": "M", "orcid": "0000-0003-4152-3855", "researcher": {"href": "https://publications.scilifelab.se/researcher/b232b70751004e9ea6b547533f901376.json"}}, {"family": "Hagenkort", "given": "Anna", "initials": "A"}, {"family": "Valerie", "given": "Nicholas C K", "initials": "NCK"}, {"family": "Rehling", "given": "Daniel", "initials": "D", "orcid": "0000-0002-8627-3469", "researcher": {"href": "https://publications.scilifelab.se/researcher/a4d521579d594e44b783a8d2e9fb98bb.json"}}, {"family": "Carter", "given": "Megan", "initials": "M"}, {"family": "Wallner", "given": "Olov", "initials": "O"}, {"family": "Koolmeister", "given": "Tobias", "initials": "T"}, {"family": "Throup", "given": "Adam", "initials": "A"}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS"}, {"family": "Alml\u00f6f", "given": "Ingrid", "initials": "I"}, {"family": "Loseva", "given": "Olga", "initials": "O"}, {"family": "Lundb\u00e4ck", "given": "Thomas", "initials": "T", "orcid": "0000-0002-8145-7808", "researcher": {"href": "https://publications.scilifelab.se/researcher/e13df787cb884549bcf333aba4e6f010.json"}}, {"family": "Axelsson", "given": "Hanna", "initials": "H", "orcid": "0000-0003-2365-1749", "researcher": {"href": "https://publications.scilifelab.se/researcher/63b88c4d11c443f39121c6d93fcff1f0.json"}}, {"family": "Regmi", "given": "Shruti", "initials": "S"}, {"family": "Sarno", "given": "Antonio", "initials": "A"}, {"family": "Kr\u00e4mer", "given": "Andreas", "initials": "A"}, {"family": "Pudelko", "given": "Linda", "initials": "L"}, {"family": "Br\u00e4utigam", "given": "Lars", "initials": "L"}, {"family": "Rasti", "given": "Azita", "initials": "A"}, {"family": "G\u00f6ttmann", "given": "Mona", "initials": "M"}, {"family": "Wiita", "given": "Elis\u00e9e", "initials": "E"}, {"family": "Kutzner", "given": "Juliane", "initials": "J"}, {"family": "Schaller", "given": "Torsten", "initials": "T", "orcid": "0000-0001-9597-4112", "researcher": {"href": "https://publications.scilifelab.se/researcher/c74944db1b4f4fe4a09079f417f8eec6.json"}}, {"family": "Kalder\u00e9n", "given": "Christina", "initials": "C"}, {"family": "C\u00e1zares-K\u00f6rner", "given": "Armando", "initials": "A"}, {"family": "Page", "given": "Brent D G", "initials": "BDG"}, {"family": "Krimpenfort", "given": "Rosa", "initials": "R"}, {"family": "Eshtad", "given": "Saeed", "initials": "S", "orcid": "0000-0001-6763-4700", "researcher": {"href": "https://publications.scilifelab.se/researcher/edf4a705cae045feb64d1d9c7f8d9646.json"}}, {"family": "Altun", "given": "Mikael", "initials": "M", "orcid": "0000-0002-6937-6124", "researcher": {"href": "https://publications.scilifelab.se/researcher/4317b773615e476694840e907b7b1a0c.json"}}, {"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications.scilifelab.se/researcher/cf1e23d9748e4868a4b5e966e423b1a9.json"}}, {"family": "Knapp", "given": "Stefan", "initials": "S", "orcid": "0000-0001-5995-6494", "researcher": {"href": "https://publications.scilifelab.se/researcher/c4d84c40612d48f280d4ead25558d835.json"}}, {"family": "Scobie", "given": "Martin", "initials": "M"}, {"family": "Homan", "given": "Evert J", "initials": "EJ"}, {"family": "Berglund", "given": "Ulrika Warpman", "initials": "UW", "orcid": "0000-0002-6372-1396", "researcher": {"href": "https://publications.scilifelab.se/researcher/a74c79d4b11346a4918f536b5a678e12.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications.scilifelab.se/researcher/d97eba9f5edf4d76a5259c4baa8366c5.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}], "type": "journal article", "published": "2020-10-00", "journal": {"title": "Nat. Chem. Biol.", "issn": "1552-4469", "volume": "16", "issue": "10", "pages": "1120-1128", "issn-l": "1552-4450"}, "abstract": "The NUDIX hydrolase NUDT15 was originally implicated in sanitizing oxidized nucleotides, but was later shown to hydrolyze the active thiopurine metabolites, 6-thio-(d)GTP, thereby dictating the clinical response of this standard-of-care treatment for leukemia and inflammatory diseases. Nonetheless, its physiological roles remain elusive. Here, we sought to develop small-molecule NUDT15 inhibitors to elucidate its biological functions and potentially to improve NUDT15-dependent chemotherapeutics. Lead compound TH1760 demonstrated low-nanomolar biochemical potency through direct and specific binding into the NUDT15 catalytic pocket and engaged cellular NUDT15 in the low-micromolar range. We also employed thiopurine potentiation as a proxy functional readout and demonstrated that TH1760 sensitized cells to 6-thioguanine through enhanced accumulation of 6-thio-(d)GTP in nucleic acids. A biochemically validated, inactive structural analog, TH7285, confirmed that increased thiopurine toxicity takes place via direct NUDT15 inhibition. In conclusion, TH1760 represents the first chemical probe for interrogating NUDT15 biology and potential therapeutic avenues.", "doi": "10.1038/s41589-020-0592-z", "pmid": "32690945", "labels": {"Protein Science Facility (PSF)": "Service", "Chemical Biology Consortium Sweden": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41589-020-0592-z"}, {"db": "pmc", "key": "PMC7610571"}, {"db": "mid", "key": "EMS118347"}], "notes": [], "created": "2020-09-25T11:44:11.217Z", "modified": "2025-10-17T13:04:28.262Z"}, {"entity": "publication", "iuid": "213dcd6a98684a7ea8372fe50ab19850", "links": {"self": {"href": "https://publications.scilifelab.se/publication/213dcd6a98684a7ea8372fe50ab19850.json"}, "display": {"href": "https://publications.scilifelab.se/publication/213dcd6a98684a7ea8372fe50ab19850"}}, "title": "Association of serum anti-centromere protein F antibodies with clinical response to infliximab in patients with rheumatoid arthritis: A prospective study.", "authors": [{"family": "Lourido", "given": "Luc\u00eda", "initials": "L"}, {"family": "Ruiz-Romero", "given": "Cristina", "initials": "C"}, {"family": "Picchi", "given": "Flor", "initials": "F"}, {"family": "Diz-Rosales", "given": "Naomi", "initials": "N"}, {"family": "Vilaboa-Gal\u00e1n", "given": "Sergio", "initials": "S"}, {"family": "Fern\u00e1ndez-L\u00f3pez", "given": "Carlos", "initials": "C"}, {"family": "Tasende", "given": "Jos\u00e9 Antonio Pinto", "initials": "JAP"}, {"family": "P\u00e9rez-Pamp\u00edn", "given": "Eva", "initials": "E"}, {"family": "Regueiro", "given": "Cristina", "initials": "C"}, {"family": "Mera-Varela", "given": "Antonio", "initials": "A"}, {"family": "Gonzalez", "given": "Antonio", "initials": "A"}, {"family": "Hambardzumyan", "given": "Karen", "initials": "K"}, {"family": "Saevarsdottir", "given": "Saedis", "initials": "S"}, {"family": "Nilsson", "given": "Peter", "initials": "P", "orcid": "0000-0002-4657-8532", "researcher": {"href": "https://publications.scilifelab.se/researcher/799bcf1cf8cf451296f4535dd4ca9dc0.json"}}, {"family": "Blanco", "given": "Francisco J", "initials": "FJ"}], "type": "journal article", "published": "2020-10-00", "journal": {"title": "Semin. Arthritis Rheum.", "issn": "1532-866X", "volume": "50", "issue": "5", "pages": "1101-1108", "issn-l": "0049-0172"}, "abstract": "One-third of rheumatoid arthritis (RA) patients demonstrate no clinical improvement after receiving tumor necrosis factor inhibitors (TNFi). The presence of serum autoantibodies is a hallmark in RA and may provide information on future response to treatment. The aim of this prospective study was to search for novel serum autoantibodies useful to predict clinical response to TNFi.\n\nThe autoantibody repertoire was profiled on RA patients treated with TNFi as a first line of biologic therapy (N = 185), who were recruited in three independent cohorts. The presence and levels of autoantibodies in serum at baseline were analysed in association with the clinical response after 24 weeks follow-up. A multiplex bead array built using antigens selected from an initial untargeted screening was employed to identify the autoantibodies on a discovery cohort (N = 50) and to verify and validate the results on verification (N = 61) and validation (N = 74) cohorts. Non-parametric tests, meta-analysis and Receiver Operating Curves (ROC) were performed in order to assess the clinical relevance of the observed findings.\n\nNovel autoantibodies were associated with the clinical response to TNFi, showing different reactivity profiles among the different TNFi. The baseline levels of IgG antibodies against Centromere protein F (CENPF), a protein related to cell proliferation, were significantly (p<0.05) increased in responders (N = 111) to infliximab (IFX) compared to non-responders (N = 44). The addition of anti-CENPF antibodies to demographic and clinical variables (age, sex, DAS28-ESR) resulted in the best model to discriminate responders, showing an area under the curve (AUC) of 0.756 (95% CI [0.639-0.874], p = 0.001). A further meta-analysis demonstrated the significant association of anti-CENPF levels with the patient's subsequent response to IFX, showing a standardized mean difference (SMD) of -0.65 (95% CI [-1.02;-0. 27], p = 0.018).\n\nOur study reveals for the first time the potential of circulating anti-CENPF antibodies to predict the clinical response to IFX before starting the treatment. This finding could be potentially useful to guide therapeutic decisions and may lead to further studies focusing on the role of CENPF on RA pathology.", "doi": "10.1016/j.semarthrit.2020.06.010", "pmid": "32920323", "labels": {"Autoimmunity and Serology Profiling": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0049-0172(20)30190-6"}], "notes": [], "created": "2020-09-15T12:16:35.815Z", "modified": "2021-11-10T12:50:02.160Z"}, {"entity": "publication", "iuid": "73ca2e71397248f8a37be2560bd5c0e7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/73ca2e71397248f8a37be2560bd5c0e7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/73ca2e71397248f8a37be2560bd5c0e7"}}, "title": "High-fat diet and estrogen impacts the colon and its transcriptome in a sex-dependent manner.", "authors": [{"family": "Hases", "given": "L", "initials": "L"}, {"family": "Archer", "given": "A", "initials": "A"}, {"family": "Indukuri", "given": "R", "initials": "R"}, {"family": "Birgersson", "given": "M", "initials": "M"}, {"family": "Savva", "given": "C", "initials": "C"}, {"family": "Korach-Andr\u00e9", "given": "M", "initials": "M"}, {"family": "Williams", "given": "C", "initials": "C"}], "type": "journal article", "published": "2020-09-30", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "16160", "issn-l": "2045-2322"}, "abstract": "There is a strong association between obesity and colorectal cancer (CRC), especially in men, whereas estrogen protects against both the metabolic syndrome and CRC. Colon is the first organ to respond to high-fat diet (HFD), and estrogen receptor beta (ER\u03b2) can attenuate CRC development. How estrogen impacts the colon under HFD and related sex differences has, however, not been investigated. To dissect this, mice were fed control diet or HFD for 13 weeks and administered receptor-selective estrogenic ligands for the last three weeks. We recorded impact on metabolism, colon crypt proliferation, macrophage infiltration, and the colon transcriptome. We found clear sex differences in the colon transcriptome and in the impact by HFD and estrogens, including on clock genes. ER\u03b1-selective activation reduced body weight and generated systemic effects, whereas ER\u03b2-selective activation had local effects in the colon, attenuating HFD-induced macrophage infiltration and epithelial cell proliferation. We here demonstrate how HFD and estrogens modulate the colon microenvironment in a sex- and ER-specific manner.", "doi": "10.1038/s41598-020-73166-1", "pmid": "32999402", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-73166-1"}, {"db": "pmc", "key": "PMC7527340"}], "notes": [], "created": "2020-12-07T16:32:31.546Z", "modified": "2024-01-16T13:48:41.674Z"}, {"entity": "publication", "iuid": "6c604e82b0474bec8f83ce513a50bfc1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6c604e82b0474bec8f83ce513a50bfc1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6c604e82b0474bec8f83ce513a50bfc1"}}, "title": "Toll-like receptors revisited; a possible role for TLR1 in lupus nephritis.", "authors": [{"family": "Yavuz", "given": "Sule", "initials": "S", "orcid": "0000-0001-5053-6426", "researcher": {"href": "https://publications.scilifelab.se/researcher/21855da83e524b939d9e7aec390e49fc.json"}}, {"family": "Bianchi", "given": "Matteo", "initials": "M"}, {"family": "Kozyrev", "given": "Sergey", "initials": "S"}, {"family": "Bolin", "given": "Karin", "initials": "K"}, {"family": "Leonard", "given": "Dag", "initials": "D"}, {"family": "Pucholt", "given": "Pascal", "initials": "P"}, {"family": "Sandling", "given": "Johanna K", "initials": "JK", "orcid": "0000-0003-1382-2321", "researcher": {"href": "https://publications.scilifelab.se/researcher/9c7bae5a05ac47eeac96547ca7336767.json"}}, {"family": "Bengtsson", "given": "Anders", "initials": "A"}, {"family": "J\u00f6nsen", "given": "Andreas", "initials": "A"}, {"family": "Rantap\u00e4\u00e4-Dahlqvist", "given": "Solbritt", "initials": "S"}, {"family": "Sj\u00f6wall", "given": "Christopher", "initials": "C", "orcid": "0000-0003-0900-2048", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe4dd47b8ca1436e8a26fdea33f5e7f6.json"}}, {"family": "Svenungsson", "given": "Elisabet", "initials": "E", "orcid": "0000-0003-3396-3244", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ab5989c3c604a96bf42b1b6f90434a0.json"}}, {"family": "Gunnarsson", "given": "Iva", "initials": "I"}, {"family": "Lindblad-Toh", "given": "Kerstin", "initials": "K", "orcid": "0000-0001-8338-0253", "researcher": {"href": "https://publications.scilifelab.se/researcher/e0063145f7d6476f80ab42f94833f4cf.json"}}, {"family": "R\u00f6nnblom", "given": "Lars", "initials": "L"}], "type": "letter", "published": "2020-09-29", "journal": {"title": "Ann. Rheum. Dis.", "issn": "1468-2060", "volume": "80", "issue": "3", "pages": "404-406", "issn-l": "0003-4967"}, "abstract": null, "doi": "10.1136/annrheumdis-2020-218373", "pmid": "32994161", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "annrheumdis-2020-218373"}, {"db": "pmc", "key": "PMC7892377"}], "notes": [], "created": "2020-12-08T23:29:04.091Z", "modified": "2021-11-10T12:46:58.369Z"}, {"entity": "publication", "iuid": "81e7c7a8721c401db24730496b0fb38d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/81e7c7a8721c401db24730496b0fb38d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/81e7c7a8721c401db24730496b0fb38d"}}, "title": "Structural Basis for GTP versus ATP Selectivity in the NMP Kinase AK3.", "authors": [{"family": "Rogne", "given": "Per", "initials": "P"}, {"family": "Dulko-Smith", "given": "Beata", "initials": "B"}, {"family": "Goodman", "given": "Jack", "initials": "J"}, {"family": "Rosselin", "given": "Marie", "initials": "M"}, {"family": "Grundstr\u00f6m", "given": "Christin", "initials": "C"}, {"family": "Hedberg", "given": "Christian", "initials": "C"}, {"family": "Nam", "given": "Kwangho", "initials": "K", "orcid": "0000-0003-0723-7839", "researcher": {"href": "https://publications.scilifelab.se/researcher/29b33d801f244b6aac48a9d626962770.json"}}, {"family": "Sauer-Eriksson", "given": "A Elisabeth", "initials": "AE", "orcid": "0000-0003-0124-0199", "researcher": {"href": "https://publications.scilifelab.se/researcher/9435049fbe2745b59e04558cc5201f95.json"}}, {"family": "Wolf-Watz", "given": "Magnus", "initials": "M", "orcid": "0000-0002-9098-7974", "researcher": {"href": "https://publications.scilifelab.se/researcher/8c6ea8f5c456428db21b1085ad541538.json"}}], "type": "journal article", "published": "2020-09-29", "journal": {"title": "Biochemistry", "issn": "1520-4995", "volume": "59", "issue": "38", "pages": "3570-3581", "issn-l": "0006-2960"}, "abstract": "ATP and GTP are exceptionally important molecules in biology with multiple, and often discrete, functions. Therefore, enzymes that bind to either of them must develop robust mechanisms to selectively utilize one or the other. Here, this specific problem is addressed by molecular studies of the human NMP kinase AK3, which uses GTP to phosphorylate AMP. AK3 plays an important role in the citric acid cycle, where it is responsible for GTP/GDP recycling. By combining a structural biology approach with functional experiments, we present a comprehensive structural and mechanistic understanding of the enzyme. We discovered that AK3 functions by recruitment of GTP to the active site, while ATP is rejected and nonproductively bound to the AMP binding site. Consequently, ATP acts as an inhibitor with respect to GTP and AMP. The overall features with specific recognition of the correct substrate and nonproductive binding by the incorrect substrate bear a strong similarity to previous findings for the ATP specific NMP kinase adenylate kinase. Taken together, we are now able to provide the fundamental principles for GTP and ATP selectivity in the large NMP kinase family. As a side-result originating from nonlinearity of chemical shifts in GTP and ATP titrations, we find that protein surfaces offer a general and weak binding affinity for both GTP and ATP. These nonspecific interactions likely act to lower the available intracellular GTP and ATP concentrations and may have driven evolution of the Michaelis constants of NMP kinases accordingly.", "doi": "10.1021/acs.biochem.0c00549", "pmid": "32822537", "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8325564"}, {"db": "mid", "key": "NIHMS1725248"}], "notes": [], "created": "2020-11-24T20:29:24.742Z", "modified": "2025-10-17T13:03:56.627Z"}, {"entity": "publication", "iuid": "69582af9423d4a7eb71db69bd379e100", "links": {"self": {"href": "https://publications.scilifelab.se/publication/69582af9423d4a7eb71db69bd379e100.json"}, "display": {"href": "https://publications.scilifelab.se/publication/69582af9423d4a7eb71db69bd379e100"}}, "title": "Streamlined and Abundant Bacterioplankton Thrive in Functional Cohorts.", "authors": [{"family": "Mondav", "given": "Rhiannon", "initials": "R", "orcid": "0000-0002-5574-5531", "researcher": {"href": "https://publications.scilifelab.se/researcher/0c421592deaa4c1a80abe628c621c901.json"}}, {"family": "Bertilsson", "given": "Stefan", "initials": "S", "orcid": "0000-0002-4265-1835", "researcher": {"href": "https://publications.scilifelab.se/researcher/2c17765c2a9f4383b5383138d11ae93f.json"}}, {"family": "Buck", "given": "Moritz", "initials": "M"}, {"family": "Langenheder", "given": "Silke", "initials": "S", "orcid": "0000-0002-5245-9935", "researcher": {"href": "https://publications.scilifelab.se/researcher/efa9e8f2174a4c7cb903b0f9b895a183.json"}}, {"family": "Lindstr\u00f6m", "given": "Eva S", "initials": "ES", "orcid": "0000-0001-8920-3071", "researcher": {"href": "https://publications.scilifelab.se/researcher/9290d334ce5a4488b8afd2af511e02ad.json"}}, {"family": "Garcia", "given": "Sarahi L", "initials": "SL", "orcid": "0000-0002-8622-0308", "researcher": {"href": "https://publications.scilifelab.se/researcher/8aabc8c17d5b4ad7872c7380301d4562.json"}}], "type": "journal article", "published": "2020-09-29", "journal": {"title": "mSystems", "issn": "2379-5077", "volume": "5", "issue": "5", "pages": null, "issn-l": "2379-5077"}, "abstract": "While fastidious microbes can be abundant and ubiquitous in their natural communities, many fail to grow axenically in laboratories due to auxotrophies or other dependencies. To overcome auxotrophies, these microbes rely on their surrounding cohort. A cohort may consist of kin (ecotypes) or more distantly related organisms (community) with the cooperation being reciprocal or nonreciprocal and expensive (Black Queen hypothesis) or costless (by-product). These metabolic partnerships (whether at single species population or community level) enable dominance by and coexistence of these lineages in nature. Here we examine the relevance of these cooperation models to explain the abundance and ubiquity of the dominant fastidious bacterioplankton of a dimictic mesotrophic freshwater lake. Using both culture-dependent (dilution mixed cultures) and culture-independent (small subunit [SSU] rRNA gene time series and environmental metagenomics) methods, we independently identified the primary cohorts of actinobacterial genera \"Candidatus Planktophila\" (acI-A) and \"Candidatus Nanopelagicus\" (acI-B) and the proteobacterial genus \"Candidatus Fonsibacter\" (LD12). While \"Ca Planktophila\" and \"Ca. Fonsibacter\" had no correlation in their natural habitat, they have the potential to be complementary in laboratory settings. We also investigated the bifunctional catalase-peroxidase enzyme KatG (a common good which \"Ca Planktophila\" is dependent upon) and its most likely providers in the lake. Further, we found that while ecotype and community cooperation combined may explain \"Ca Planktophila\" population abundance, the success of \"Ca. Nanopelagicus\" and \"Ca. Fonsibacter\" is better explained as a community by-product. Ecotype differentiation of \"Ca. Fonsibacter\" as a means of escaping predation was supported but not for overcoming auxotrophies.IMPORTANCE This study examines evolutionary and ecological relationships of three of the most ubiquitous and abundant freshwater bacterial genera: \"Ca Planktophila\" (acI-A), \"Ca. Nanopelagicus\" (acI-B), and \"Ca. Fonsibacter\" (LD12). Due to high abundance, these genera might have a significant influence on nutrient cycling in freshwaters worldwide, and this study adds a layer of understanding to how seemingly competing clades of bacteria can coexist by having different cooperation strategies. Our synthesis ties together network and ecological theory with empirical evidence and lays out a framework for how the functioning of populations within complex microbial communities can be studied.", "doi": "10.1128/mSystems.00316-20", "pmid": "32994284", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "5/5/e00316-20"}, {"db": "pmc", "key": "PMC7527133"}], "notes": [], "created": "2020-12-08T23:35:11.349Z", "modified": "2024-01-16T13:48:41.686Z"}, {"entity": "publication", "iuid": "35f57851b81546e785433040d1f08581", "links": {"self": {"href": "https://publications.scilifelab.se/publication/35f57851b81546e785433040d1f08581.json"}, "display": {"href": "https://publications.scilifelab.se/publication/35f57851b81546e785433040d1f08581"}}, "title": "Reconstruction of the birth of a male sex chromosome present in Atlantic herring.", "authors": [{"family": "Rafati", "given": "Nima", "initials": "N"}, {"family": "Chen", "given": "Junfeng", "initials": "J"}, {"family": "Herpin", "given": "Amaury", "initials": "A"}, {"family": "Pettersson", "given": "Mats E", "initials": "ME"}, {"family": "Han", "given": "Fan", "initials": "F"}, {"family": "Feng", "given": "Chungang", "initials": "C"}, {"family": "Wallerman", "given": "Ola", "initials": "O"}, {"family": "Rubin", "given": "Carl-Johan", "initials": "CJ"}, {"family": "P\u00e9ron", "given": "Sandrine", "initials": "S"}, {"family": "Cocco", "given": "Arianna", "initials": "A"}, {"family": "Larsson", "given": "M\u00e5rten", "initials": "M"}, {"family": "Tr\u00f6tschel", "given": "Christian", "initials": "C"}, {"family": "Poetsch", "given": "Ansgar", "initials": "A", "orcid": "0000-0002-7540-3475", "researcher": {"href": "https://publications.scilifelab.se/researcher/24924a964a1e4e9abd93d50ca404a680.json"}}, {"family": "Korsching", "given": "Kai", "initials": "K"}, {"family": "B\u00f6nigk", "given": "Wolfgang", "initials": "W"}, {"family": "K\u00f6rschen", "given": "Heinz G", "initials": "HG"}, {"family": "Berg", "given": "Florian", "initials": "F", "orcid": "0000-0003-1543-8112", "researcher": {"href": "https://publications.scilifelab.se/researcher/902b6c39c4f5463ea25888c17732fc3e.json"}}, {"family": "Folkvord", "given": "Arild", "initials": "A", "orcid": "0000-0002-4763-0590", "researcher": {"href": "https://publications.scilifelab.se/researcher/18e48870c7654bf0898cb9ff2a064b99.json"}}, {"family": "Kaupp", "given": "U Benjamin", "initials": "UB", "orcid": "0000-0002-0696-6397", "researcher": {"href": "https://publications.scilifelab.se/researcher/e94d12b7c4624985b0f6f7c8b798c969.json"}}, {"family": "Schartl", "given": "Manfred", "initials": "M", "orcid": "0000-0001-9882-5948", "researcher": {"href": "https://publications.scilifelab.se/researcher/5f97783b5013409ebc1a6bd2df5ca92c.json"}}, {"family": "Andersson", "given": "Leif", "initials": "L", "orcid": "0000-0002-4085-6968", "researcher": {"href": "https://publications.scilifelab.se/researcher/bd3343c12f994b1fabcae23027d3a76d.json"}}], "type": "journal article", "published": "2020-09-29", "journal": {"title": "Proc. Natl. Acad. Sci. U.S.A.", "issn": "1091-6490", "volume": "117", "issue": "39", "pages": "24359-24368", "issn-l": "0027-8424"}, "abstract": "The mechanisms underlying sex determination are astonishingly plastic. Particularly the triggers for the molecular machinery, which recalls either the male or female developmental program, are highly variable and have evolved independently and repeatedly. Fish show a huge variety of sex determination systems, including both genetic and environmental triggers. The advent of sex chromosomes is assumed to stabilize genetic sex determination. However, because sex chromosomes are notoriously cluttered with repetitive DNA and pseudogenes, the study of their evolution is hampered. Here we reconstruct the birth of a Y chromosome present in the Atlantic herring. The region is tiny (230 kb) and contains only three intact genes. The candidate male-determining gene BMPR1BBY encodes a truncated form of a BMP1B receptor, which originated by gene duplication and translocation and underwent rapid protein evolution. BMPR1BBY phosphorylates SMADs in the absence of ligand and thus has the potential to induce testis formation. The Y region also contains two genes encoding subunits of the sperm-specific Ca2+ channel CatSper required for male fertility. The herring Y chromosome conforms with a characteristic feature of many sex chromosomes, namely, suppressed recombination between a sex-determining factor and genes that are beneficial for the given sex. However, the herring Y differs from other sex chromosomes in that suppression of recombination is restricted to an \u223c500-kb region harboring the male-specific and sex-associated regions. As a consequence, any degeneration on the herring Y chromosome is restricted to those genes located in the small region affected by suppressed recombination.", "doi": "10.1073/pnas.2009925117", "pmid": "32938798", "labels": {"Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "2009925117"}, {"db": "pmc", "key": "PMC7533707"}], "notes": [], "created": "2020-09-24T13:52:16.130Z", "modified": "2024-01-16T13:48:41.694Z"}, {"entity": "publication", "iuid": "6e2a1fc431c64a6086d711f8beca0048", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6e2a1fc431c64a6086d711f8beca0048.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6e2a1fc431c64a6086d711f8beca0048"}}, "title": "MAIT cell activation and dynamics associated with COVID-19 disease severity.", "authors": [{"family": "Parrot", "given": "Tiphaine", "initials": "T", "orcid": "0000-0001-9625-6825", "researcher": {"href": "https://publications.scilifelab.se/researcher/6ae2982949a644f59bcfc88d0e3bf9c4.json"}}, {"family": "Gorin", "given": "Jean-Baptiste", "initials": "JB", "orcid": "0000-0003-4605-1375", "researcher": {"href": "https://publications.scilifelab.se/researcher/a623ffbc0a19427aabd47ad6f047e49d.json"}}, {"family": "Ponzetta", "given": "Andrea", "initials": "A", "orcid": "0000-0003-3224-802X", "researcher": {"href": "https://publications.scilifelab.se/researcher/8b06c3ab1bae404dba4ec9a1eee4f78b.json"}}, {"family": "Maleki", "given": "Kimia T", "initials": "KT", "orcid": "0000-0001-5382-5477", "researcher": {"href": "https://publications.scilifelab.se/researcher/b691252c7d7446788d0a10f0648ef47f.json"}}, {"family": "Kammann", "given": "Tobias", "initials": "T", "orcid": "0000-0002-8433-036X", "researcher": {"href": "https://publications.scilifelab.se/researcher/ead9a21a35e34fd092774ae13a211255.json"}}, {"family": "Emg\u00e5rd", "given": "Johanna", "initials": "J"}, {"family": "Perez-Potti", "given": "Andr\u00e9", "initials": "A", "orcid": "0000-0002-5998-5700", "researcher": {"href": "https://publications.scilifelab.se/researcher/fbfe371f142840bc9470b37777ac1f2f.json"}}, {"family": "Sekine", "given": "Takuya", "initials": "T", "orcid": "0000-0001-7649-0593", "researcher": {"href": "https://publications.scilifelab.se/researcher/42434c4f0f504dcd82e5830a727d5a04.json"}}, {"family": "Rivera-Ballesteros", "given": "Olga", "initials": "O", "orcid": "0000-0001-6949-4270", "researcher": {"href": "https://publications.scilifelab.se/researcher/8b48f38b946d4fbc9d687da130f2e661.json"}}, {"family": "Karolinska COVID-19 Study Group", "given": "", "initials": ""}, {"family": "Gredmark-Russ", "given": "Sara", "initials": "S", "orcid": "0000-0002-2446-4323", "researcher": {"href": "https://publications.scilifelab.se/researcher/3f7958a9ee7748cf8806253a7aeef673.json"}}, {"family": "Rooyackers", "given": "Olav", "initials": "O", "orcid": "0000-0002-3391-5448", "researcher": {"href": "https://publications.scilifelab.se/researcher/52f4fd2e5e204e598aa5087ff3f13680.json"}}, {"family": "Folkesson", "given": "Elin", "initials": "E", "orcid": "0000-0002-6585-6235", "researcher": {"href": "https://publications.scilifelab.se/researcher/82777b8f48324c58bcad72799d71fd4a.json"}}, {"family": "Eriksson", "given": "Lars I", "initials": "LI"}, {"family": "Norrby-Teglund", "given": "Anna", "initials": "A", "orcid": "0000-0001-9372-1795", "researcher": {"href": "https://publications.scilifelab.se/researcher/25c11b43fc984bbca28fcc5bbf211d58.json"}}, {"family": "Ljunggren", "given": "Hans-Gustaf", "initials": "HG"}, {"family": "Bj\u00f6rkstr\u00f6m", "given": "Niklas K", "initials": "NK", "orcid": "0000-0002-0967-076X", "researcher": {"href": "https://publications.scilifelab.se/researcher/bf38521350ae490099f01bda1d10be4c.json"}}, {"family": "Aleman", "given": "Soo", "initials": "S"}, {"family": "Buggert", "given": "Marcus", "initials": "M", "orcid": "0000-0003-0633-1719", "researcher": {"href": "https://publications.scilifelab.se/researcher/9a54e4b5136642eeafa77ac5118a0c81.json"}}, {"family": "Klingstr\u00f6m", "given": "Jonas", "initials": "J", "orcid": "0000-0001-9076-1441", "researcher": {"href": "https://publications.scilifelab.se/researcher/95c1b345ae434fb383b7fe6a1d053c80.json"}}, {"family": "Str\u00e5lin", "given": "Kristoffer", "initials": "K", "orcid": "0000-0002-8801-3169", "researcher": {"href": "https://publications.scilifelab.se/researcher/a6ffa1185f4142b7ab7c372c0c139df6.json"}}, {"family": "Sandberg", "given": "Johan K", "initials": "JK", "orcid": "0000-0002-6275-0750", "researcher": {"href": "https://publications.scilifelab.se/researcher/7468c415a46645a3a4c3d28badcff954.json"}}], "type": "journal article", "published": "2020-09-28", "journal": {"title": "Sci Immunol", "issn": "2470-9468", "volume": "5", "issue": "51", "issn-l": null}, "abstract": "Severe COVID-19 is characterized by excessive inflammation of the lower airways. The balance of protective versus pathological immune responses in COVID-19 is incompletely understood. Mucosa-associated invariant T (MAIT) cells are antimicrobial T cells that recognize bacterial metabolites, and can also function as innate-like sensors and mediators of antiviral responses. Here, we investigated the MAIT cell compartment in COVID-19 patients with moderate and severe disease, as well as in convalescence. We show profound and preferential decline in MAIT cells in the circulation of patients with active disease paired with strong activation. Furthermore, transcriptomic analyses indicated significant MAIT cell enrichment and pro-inflammatory IL-17A bias in the airways. Unsupervised analysis identified MAIT cell CD69high and CXCR3low immunotypes associated with poor clinical outcome. MAIT cell levels normalized in the convalescent phase, consistent with dynamic recruitment to the tissues and later release back into the circulation when disease is resolved. These findings indicate that MAIT cells are engaged in the immune response against SARS-CoV-2 and suggest their possible involvement in COVID-19 immunopathogenesis.", "doi": "10.1126/sciimmunol.abe1670", "pmid": "32989174", "labels": {"Affinity Proteomics Stockholm": "Service"}, "xrefs": [{"db": "pii", "key": "5/51/eabe1670"}, {"db": "pmc", "key": "PMC7857393"}], "notes": [], "created": "2020-12-10T16:30:01.335Z", "modified": "2021-11-10T12:47:01.812Z"}, {"entity": "publication", "iuid": "aa03133a8f9c405f99b8e8738efe11b9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/aa03133a8f9c405f99b8e8738efe11b9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/aa03133a8f9c405f99b8e8738efe11b9"}}, "title": "Inducible Deletion of YAP and TAZ in Adult Mouse Smooth Muscle Causes Rapid and Lethal Colonic Pseudo-Obstruction.", "authors": [{"family": "Daoud", "given": "Fatima", "initials": "F"}, {"family": "Holmberg", "given": "Johan", "initials": "J"}, {"family": "Alajbegovic", "given": "Azra", "initials": "A"}, {"family": "Grossi", "given": "Mario", "initials": "M"}, {"family": "Rippe", "given": "Catarina", "initials": "C"}, {"family": "Sw\u00e4rd", "given": "Karl", "initials": "K"}, {"family": "Albinsson", "given": "Sebastian", "initials": "S"}], "type": "journal article", "published": "2020-09-28", "journal": {"title": "Cellular and Molecular Gastroenterology and Hepatology", "issn": "2352-345X", "volume": "11", "issue": "2", "pages": "623-637", "issn-l": "2352-345X"}, "abstract": "YAP (Yap1) and TAZ (Wwtr1) are transcriptional co-activators and downstream effectors of the Hippo pathway, which play crucial roles in organ size control and cancer pathogenesis. Genetic deletion of YAP/TAZ has shown their critical importance for embryonic development of the heart, vasculature, and gastrointestinal mesenchyme. The aim of this study was to determine the functional role of YAP/TAZ in adult smooth muscle cells in vivo.\n\nBecause YAP and TAZ are mutually redundant, we used YAP/TAZ double-floxed mice crossed with mice that express tamoxifen-inducible CreERT2 recombinase driven by the smooth muscle-specific myosin heavy chain promoter.\n\nDouble-knockout of YAP/TAZ in adult smooth muscle causes lethality within 2 weeks, mainly owing to colonic pseudo-obstruction, characterized by severe distension and fecal impaction. RNA sequencing in colon and urinary bladder showed that smooth muscle markers and muscarinic receptors were down-regulated in the YAP/TAZ knockout. The same transcripts also correlated with YAP/TAZ in the human colon. Myograph experiments showed reduced contractility to depolarization by potassium chloride and a nearly abolished muscarinic contraction and spontaneous activity in colon rings of YAP/TAZ knockout.\n\nYAP and TAZ in smooth muscle are guardians of colonic contractility and control expression of contractile proteins and muscarinic receptors. The knockout model has features of human chronic intestinal pseudo-obstruction and may be useful for studying this disease.", "doi": "10.1016/j.jcmgh.2020.09.014", "pmid": "32992050", "labels": {"Clinical Genomics Lund": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "S2352-345X(20)30157-0"}, {"db": "pmc", "key": "PMC7806867"}], "notes": [], "created": "2021-11-23T13:28:09.182Z", "modified": "2021-11-23T13:28:09.193Z"}, {"entity": "publication", "iuid": "cde158ede680439a93d1a55b6b0aef96", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cde158ede680439a93d1a55b6b0aef96.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cde158ede680439a93d1a55b6b0aef96"}}, "title": "Labile Dissolved Organic Matter Compound Characteristics Select for Divergence in Marine Bacterial Activity and Transcription.", "authors": [{"family": "Pontiller", "given": "Benjamin", "initials": "B"}, {"family": "Mart\u00ednez-Garc\u00eda", "given": "Sandra", "initials": "S"}, {"family": "Lundin", "given": "Daniel", "initials": "D"}, {"family": "Pinhassi", "given": "Jarone", "initials": "J"}], "type": "journal article", "published": "2020-09-25", "journal": {"title": "Front Microbiol", "issn": "1664-302X", "volume": "11", "issue": null, "pages": "588778", "issn-l": "1664-302X"}, "abstract": "Bacteria play a key role in the planetary carbon cycle partly because they rapidly assimilate labile dissolved organic matter (DOM) in the ocean. However, knowledge of the molecular mechanisms at work when bacterioplankton metabolize distinct components of the DOM pool is still limited. We, therefore, conducted seawater culture enrichment experiments with ecologically relevant DOM, combining both polymer and monomer model compounds for distinct compound classes. This included carbohydrates (polysaccharides vs. monosaccharides), proteins (polypeptides vs. amino acids), and nucleic acids (DNA vs. nucleotides). We noted pronounced changes in bacterial growth, activity, and transcription related to DOM characteristics. Transcriptional responses differed between compound classes, with distinct gene sets (\"core genes\") distinguishing carbohydrates, proteins, and nucleic acids. Moreover, we found a strong divergence in functional transcription at the level of particular monomers and polymers (i.e., the condensation state), primarily in the carbohydrates and protein compound classes. These specific responses included a variety of cellular and metabolic processes that were mediated by distinct bacterial taxa, suggesting pronounced functional partitioning of organic matter. Collectively, our findings show that two important facets of DOM, compound class and condensation state, shape bacterial gene expression, and ultimately select for distinct bacterial (functional) groups. This emphasizes the interdependency of marine bacteria and labile carbon compounds for regulating the transformation of DOM in surface waters.", "doi": "10.3389/fmicb.2020.588778", "pmid": "33101262", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7546218"}], "notes": [], "created": "2020-12-07T16:36:37.841Z", "modified": "2024-01-16T13:48:41.701Z"}, {"entity": "publication", "iuid": "e7e7ddd7c2234dac93697ac7e3483c70", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e7e7ddd7c2234dac93697ac7e3483c70.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e7e7ddd7c2234dac93697ac7e3483c70"}}, "title": "Increased antibiotic efficacy and noninvasive monitoring of Staphylococcus epidermidis biofilms using per-cysteamine-substituted \u03b3-cyclodextrin - A delivery effect validated by fluorescence microscopy.", "authors": [{"family": "Thomsen", "given": "Hanna", "initials": "H"}, {"family": "Agnes", "given": "Marco", "initials": "M"}, {"family": "Uwangue", "given": "Owens", "initials": "O"}, {"family": "Persson", "given": "Linn\u00e9a", "initials": "L"}, {"family": "Mattsson", "given": "Matilda", "initials": "M"}, {"family": "Graf", "given": "Fabrice E", "initials": "FE"}, {"family": "Kasimati", "given": "Eleni-Marina", "initials": "EM"}, {"family": "Yannakopoulou", "given": "Konstantina", "initials": "K"}, {"family": "Ericson", "given": "Marica B", "initials": "MB"}, {"family": "Farewell", "given": "Anne", "initials": "A"}], "type": "journal article", "published": "2020-09-25", "journal": {"title": "Int J Pharm", "issn": "1873-3476", "volume": "587", "pages": "119646", "issn-l": "0378-5173"}, "abstract": "Limited and poor delivery of antibiotics is cited as one reason for the difficulty in treating antibiotic-resistant biofilms associated with chronic infections. We investigate the effectiveness of a positively charged, single isomer cyclodextrin derivative, octakis[6-(2-aminoethylthio)-6-deoxy]-\u03b3-CD (\u03b3Cys) to improve the delivery of antibiotics to biofilms. Using multiphoton laser scanning microscopy complemented with super-resolution fluorescence microscopy, we showed that \u03b3Cys tagged with fluorescein (FITC) is uniformly distributed throughout live S. epidermidis biofilm cultures in vitro and results suggest it is localized extracellularly in the biofilm matrix. NMR spectroscopic data in aqueous solution confirm that \u03b3Cys forms inclusion complexes with both the antibiotics oxacillin and rifampicin. Efficacy of \u03b3Cys/antibiotic (oxacillin and rifampicin) was measured in the biofilms. While treatment with \u03b3Cys/oxacillin had little improvement over oxacillin alone, \u03b3Cys/rifampicin reduced the biofilm viability to background levels demonstrating a remarkable improvement over rifampicin alone. The strong synergistic effect for \u03b3Cys/rifampicin is at this stage not clearly understood, but plausible explanations are related to increased solubility of rifampicin upon complexation and/or synergistic interference with components of the biofilm. The results demonstrate that designed cyclodextrin nanocarriers, like \u03b3Cys, efficiently deliver suitable antibiotics to biofilms and that fluorescence microscopy offers a novel approach for mechanistic investigations.", "doi": "10.1016/j.ijpharm.2020.119646", "pmid": "32679261", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S0378-5173(20)30630-X"}], "notes": [], "created": "2023-02-16T08:10:09.500Z", "modified": "2023-02-16T08:10:09.503Z"}, {"entity": "publication", "iuid": "f360a76b9b594b51a16269f0f9d37e3c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f360a76b9b594b51a16269f0f9d37e3c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f360a76b9b594b51a16269f0f9d37e3c"}}, "title": "High-Resolution Imaging of Tumor Spheroids and Organoids Enabled by Expansion Microscopy.", "authors": [{"family": "Edwards", "given": "Steven J", "initials": "SJ"}, {"family": "Carannante", "given": "Valentina", "initials": "V"}, {"family": "Kuhnigk", "given": "Kyra", "initials": "K"}, {"family": "Ring", "given": "Henrik", "initials": "H"}, {"family": "Tararuk", "given": "Tatsiana", "initials": "T"}, {"family": "Hallb\u00f6\u00f6k", "given": "Finn", "initials": "F"}, {"family": "Blom", "given": "Hans", "initials": "H", "orcid": "0000-0002-5584-9170", "researcher": {"href": "https://publications.scilifelab.se/researcher/3ce356a74dc84e0ea6af85397f11d869.json"}}, {"family": "\u00d6nfelt", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Brismar", "given": "Hjalmar", "initials": "H", "orcid": "0000-0003-0578-4003", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ec23336e2ef4e298f340876f1136dce.json"}}], "type": "journal article", "published": "2020-09-24", "journal": {"title": "Front Mol Biosci", "issn": "2296-889X", "issn-l": "2296-889X", "volume": "7", "issue": null, "pages": "208"}, "abstract": "Three-dimensional cell cultures are able to better mimic the physiology and cellular environments found in tissues in vivo compared to cells grown in two dimensions. In order to study the structure and function of cells in 3-D cultures, light microscopy is frequently used. The preparation of 3-D cell cultures for light microscopy is often destructive, including physical sectioning of the samples, which can result in the loss of 3-D information. In order to probe the structure of 3-D cell cultures at high resolution, we have explored the use of expansion microscopy and compared it to a simple immersion clearing protocol. We provide a practical method for the study of spheroids, organoids and tumor-infiltrating immune cells at high resolution without the loss of spatial organization. Expanded samples are highly transparent, enabling high-resolution imaging over extended volumes by significantly reducing light scatter and absorption. In addition, the hydrogel-like nature of expanded samples enables homogenous antibody labeling of dense epitopes throughout the sample volume. The improved labeling and image quality achieved in expanded samples revealed details in the center of the organoid which were previously only observable following serial sectioning. In comparison to chemically cleared spheroids, the improved signal-to-background ratio of expanded samples greatly improved subsequent methods for image segmentation and analysis.", "doi": "10.3389/fmolb.2020.00208", "pmid": "33195398", "labels": {"Integrated Microscopy Technologies Stockholm": "Technology development"}, "xrefs": [{"db": "pmc", "key": "PMC7543521"}], "notes": "https://www.frontiersin.org/articles/10.3389/fmolb.2020.00208/full", "created": "2020-09-16T09:11:47.747Z", "modified": "2021-11-10T12:47:05.706Z"}, {"entity": "publication", "iuid": "93a54b75e2294c589b968a9de83166e9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/93a54b75e2294c589b968a9de83166e9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/93a54b75e2294c589b968a9de83166e9"}}, "title": "Therapeutic targeting of KSP in preclinical models of high-risk neuroblastoma.", "authors": [{"family": "Hansson", "given": "Karin", "initials": "K", "orcid": "0000-0002-6993-7673", "researcher": {"href": "https://publications.scilifelab.se/researcher/1c0c991068644f61b10c986deff8fb7f.json"}}, {"family": "Radke", "given": "Katarzyna", "initials": "K", "orcid": "0000-0002-4460-0812", "researcher": {"href": "https://publications.scilifelab.se/researcher/ad483c946ce244fa898cadb6238e970d.json"}}, {"family": "Aaltonen", "given": "Kristina", "initials": "K", "orcid": "0000-0001-5104-735X", "researcher": {"href": "https://publications.scilifelab.se/researcher/68a63e2719d246a99fc51e8e3ed05cee.json"}}, {"family": "Saarela", "given": "Jani", "initials": "J", "orcid": "0000-0001-7306-7175", "researcher": {"href": "https://publications.scilifelab.se/researcher/c5febb7d8bc04ecb9664e3be19f4bb37.json"}}, {"family": "Ma\u00f1as", "given": "Adriana", "initials": "A", "orcid": "0000-0002-6955-1754", "researcher": {"href": "https://publications.scilifelab.se/researcher/7220571c605044f980abf2933374aa1a.json"}}, {"family": "Sj\u00f6lund", "given": "Jonas", "initials": "J", "orcid": "0000-0002-6992-3415", "researcher": {"href": "https://publications.scilifelab.se/researcher/eccac6b320244409879d5bac740f5202.json"}}, {"family": "Smith", "given": "Emma M", "initials": "EM", "orcid": "0000-0003-0609-4864", "researcher": {"href": "https://publications.scilifelab.se/researcher/4b453bd8533f4359b50e71c5aafa3d2a.json"}}, {"family": "Pietras", "given": "Kristian", "initials": "K", "orcid": "0000-0001-6738-4705", "researcher": {"href": "https://publications.scilifelab.se/researcher/5be0a3ec07654822a91df964eab1d6e4.json"}}, {"family": "P\u00e5hlman", "given": "Sven", "initials": "S"}, {"family": "Wennerberg", "given": "Krister", "initials": "K", "orcid": "0000-0002-1352-4220", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a447e220e144c63a907f9c824ccc9da.json"}}, {"family": "Gisselsson", "given": "David", "initials": "D"}, {"family": "Bexell", "given": "Daniel", "initials": "D", "orcid": "0000-0001-9426-9550", "researcher": {"href": "https://publications.scilifelab.se/researcher/dda650768a264d93a80f40da6cb8d7e1.json"}}], "type": "journal article", "published": "2020-09-23", "journal": {"title": "Sci Transl Med", "issn": "1946-6242", "volume": "12", "issue": "562", "issn-l": "1946-6234"}, "abstract": "Neuroblastoma is a childhood malignancy with often dismal prognosis; relapse is common despite intense treatment. Here, we used human tumor organoids representing multiple MYCN-amplified high-risk neuroblastomas to perform a high-throughput drug screen with approved or emerging oncology drugs. Tumor-selective effects were calculated using drug sensitivity scores. Several drugs with previously unreported anti-neuroblastoma effects were identified by stringent selection criteria. ARRY-520, an inhibitor of kinesin spindle protein (KSP), was among those causing reduced viability. High expression of the KSP-encoding gene KIF11 was associated with poor outcome in neuroblastoma. Genome-scale loss-of-function screens in hundreds of human cancer cell lines across 22 tumor types revealed that KIF11 is particularly important for neuroblastoma cell viability. KSP inhibition in neuroblastoma patient-derived xenograft (PDX) cells resulted in the formation of abnormal monoastral spindles, mitotic arrest, up-regulation of mitosis-associated genes, and apoptosis. In vivo, KSP inhibition caused regression of MYCN-amplified neuroblastoma PDX tumors. Furthermore, treatment of mice harboring orthotopic neuroblastoma PDX tumors resulted in increased survival. Our results suggested that KSP inhibition could be a promising treatment strategy in children with high-risk neuroblastoma.", "doi": "10.1126/scitranslmed.aba4434", "pmid": "32967973", "labels": {"Clinical Genomics Lund": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "12/562/eaba4434"}], "notes": [], "created": "2021-11-24T07:56:38.972Z", "modified": "2021-11-24T07:56:39.291Z"}, {"entity": "publication", "iuid": "a3077264f8cc4b788b7506ddb9b5546f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a3077264f8cc4b788b7506ddb9b5546f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a3077264f8cc4b788b7506ddb9b5546f"}}, "title": "Dental cell type atlas reveals stem and differentiated cell types in mouse and human teeth.", "authors": [{"family": "Krivanek", "given": "Jan", "initials": "J", "orcid": "0000-0002-7590-187X", "researcher": {"href": "https://publications.scilifelab.se/researcher/e716ca0e1b464dd9850687d8f5aa6758.json"}}, {"family": "Soldatov", "given": "Ruslan A", "initials": "RA"}, {"family": "Kastriti", "given": "Maria Eleni", "initials": "ME"}, {"family": "Chontorotzea", "given": "Tatiana", "initials": "T"}, {"family": "Herdina", "given": "Anna Nele", "initials": "AN"}, {"family": "Petersen", "given": "Julian", "initials": "J", "orcid": "0000-0002-7444-0610", "researcher": {"href": "https://publications.scilifelab.se/researcher/74d20bbfd5a540a58aac82ada8d80b0d.json"}}, {"family": "Szarowska", "given": "Bara", "initials": "B"}, {"family": "Landova", "given": "Marie", "initials": "M"}, {"family": "Matejova", "given": "Veronika Kovar", "initials": "VK"}, {"family": "Holla", "given": "Lydie Izakovicova", "initials": "LI", "orcid": "0000-0002-7610-8929", "researcher": {"href": "https://publications.scilifelab.se/researcher/2c239a2405d04c14ad3d1a08759d1457.json"}}, {"family": "Kuchler", "given": "Ulrike", "initials": "U"}, {"family": "Zdrilic", "given": "Ivana Vidovic", "initials": "IV"}, {"family": "Vijaykumar", "given": "Anushree", "initials": "A", "orcid": "0000-0002-9311-8715", "researcher": {"href": "https://publications.scilifelab.se/researcher/2e151e4b5e2d49ab925969f0b425ed58.json"}}, {"family": "Balic", "given": "Anamaria", "initials": "A", "orcid": "0000-0001-6796-1197", "researcher": {"href": "https://publications.scilifelab.se/researcher/53dc6465cd6b44c38e2e29aeb3f077a7.json"}}, {"family": "Marangoni", "given": "Pauline", "initials": "P"}, {"family": "Klein", "given": "Ophir D", "initials": "OD", "orcid": "0000-0002-6254-7082", "researcher": {"href": "https://publications.scilifelab.se/researcher/aab94ed0b4f549ef941147b2ffbe27c9.json"}}, {"family": "Neves", "given": "Vitor C M", "initials": "VCM"}, {"family": "Yianni", "given": "Val", "initials": "V", "orcid": "0000-0001-9857-7577", "researcher": {"href": "https://publications.scilifelab.se/researcher/aa7601d7378f41319dfb7cc9210ccfea.json"}}, {"family": "Sharpe", "given": "Paul T", "initials": "PT", "orcid": "0000-0003-2116-9561", "researcher": {"href": "https://publications.scilifelab.se/researcher/d32e7381201b4d9e932b44da8f37e3b1.json"}}, {"family": "Harkany", "given": "Tibor", "initials": "T"}, {"family": "Metscher", "given": "Brian D", "initials": "BD", "orcid": "0000-0002-6514-4406", "researcher": {"href": "https://publications.scilifelab.se/researcher/5ab0055dc0374b4bb88f9bfbb2e0313a.json"}}, {"family": "Baj\u00e9noff", "given": "Marc", "initials": "M"}, {"family": "Mina", "given": "Mina", "initials": "M"}, {"family": "Fried", "given": "Kaj", "initials": "K"}, {"family": "Kharchenko", "given": "Peter V", "initials": "PV", "orcid": "0000-0002-6036-5875", "researcher": {"href": "https://publications.scilifelab.se/researcher/a67002dec1264bf2865da0017405ee9b.json"}}, {"family": "Adameyko", "given": "Igor", "initials": "I", "orcid": "0000-0001-5471-0356", "researcher": {"href": "https://publications.scilifelab.se/researcher/346f484a56cb4ad5b866b194ccd44e4f.json"}}], "type": "journal article", "published": "2020-09-23", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "11", "issue": "1", "pages": "4816", "issn-l": "2041-1723"}, "abstract": "Understanding cell types and mechanisms of dental growth is essential for reconstruction and engineering of teeth. Therefore, we investigated cellular composition of growing and non-growing mouse and human teeth. As a result, we report an unappreciated cellular complexity of the continuously-growing mouse incisor, which suggests a coherent model of cell dynamics enabling unarrested growth. This model relies on spatially-restricted stem, progenitor and differentiated populations in the epithelial and mesenchymal compartments underlying the coordinated expansion of two major branches of pulpal cells and diverse epithelial subtypes. Further comparisons of human and mouse teeth yield both parallelisms and differences in tissue heterogeneity and highlight the specifics behind growing and non-growing modes. Despite being similar at a coarse level, mouse and human teeth reveal molecular differences and species-specific cell subtypes suggesting possible evolutionary divergence. Overall, here we provide an atlas of human and mouse teeth with a focus on growth and differentiation.", "doi": "10.1038/s41467-020-18512-7", "pmid": "32968047", "labels": {"Eukaryotic Single Cell Genomics (ESCG)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-18512-7"}, {"db": "pmc", "key": "PMC7511944"}], "notes": [], "created": "2021-12-10T20:15:06.566Z", "modified": "2022-01-03T10:04:22.911Z"}, {"entity": "publication", "iuid": "6cafceb7951749a2ad866112832a56e3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6cafceb7951749a2ad866112832a56e3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6cafceb7951749a2ad866112832a56e3"}}, "title": "Sources of variation in cell-type RNA-Seq profiles.", "authors": [{"family": "Gustafsson", "given": "Johan", "initials": "J", "orcid": "0000-0001-5072-2659", "researcher": {"href": "https://publications.scilifelab.se/researcher/bd5fda1ac79e49c185ba6f4dfcdff5fc.json"}}, {"family": "Held", "given": "Felix", "initials": "F"}, {"family": "Robinson", "given": "Jonathan L", "initials": "JL"}, {"family": "Bj\u00f6rnson", "given": "Elias", "initials": "E"}, {"family": "J\u00f6rnsten", "given": "Rebecka", "initials": "R"}, {"family": "Nielsen", "given": "Jens", "initials": "J", "orcid": "0000-0002-9955-6003", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a596e289be4438a8a2653b1f25fea8b.json"}}], "type": "comparative study", "published": "2020-09-21", "journal": {"title": "PLoS ONE", "issn": "1932-6203", "volume": "15", "issue": "9", "pages": "e0239495", "issn-l": "1932-6203"}, "abstract": "Cell-type specific gene expression profiles are needed for many computational methods operating on bulk RNA-Seq samples, such as deconvolution of cell-type fractions and digital cytometry. However, the gene expression profile of a cell type can vary substantially due to both technical factors and biological differences in cell state and surroundings, reducing the efficacy of such methods. Here, we investigated which factors contribute most to this variation. We evaluated different normalization methods, quantified the variance explained by different factors, evaluated the effect on deconvolution of cell type fractions, and examined the differences between UMI-based single-cell RNA-Seq and bulk RNA-Seq. We investigated a collection of publicly available bulk and single-cell RNA-Seq datasets containing B and T cells, and found that the technical variation across laboratories is substantial, even for genes specifically selected for deconvolution, and this variation has a confounding effect on deconvolution. Tissue of origin is also a substantial factor, highlighting the challenge of using cell type profiles derived from blood with mixtures from other tissues. We also show that much of the differences between UMI-based single-cell and bulk RNA-Seq methods can be explained by the number of read duplicates per mRNA molecule in the single-cell sample. Our work shows the importance of either matching or correcting for technical factors when creating cell-type specific gene expression profiles that are to be used together with bulk samples.", "doi": "10.1371/journal.pone.0239495", "pmid": "32956417", "labels": {"Systems Biology": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "PONE-D-20-18758"}, {"db": "pmc", "key": "PMC7505444"}], "notes": [], "created": "2020-12-10T11:09:36.486Z", "modified": "2021-11-10T12:47:07.845Z"}, {"entity": "publication", "iuid": "32d06cd19e9b474391c7e5f6ed354f57", "links": {"self": {"href": "https://publications.scilifelab.se/publication/32d06cd19e9b474391c7e5f6ed354f57.json"}, "display": {"href": "https://publications.scilifelab.se/publication/32d06cd19e9b474391c7e5f6ed354f57"}}, "title": "Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples.", "authors": [{"family": "Bailey", "given": "Matthew H", "initials": "MH", "orcid": "0000-0003-4526-9727", "researcher": {"href": "https://publications.scilifelab.se/researcher/b2acdd4c993a403b825e0509aaae6a46.json"}}, {"family": "Meyerson", "given": "William U", "initials": "WU"}, {"family": "Dursi", "given": "Lewis Jonathan", "initials": "LJ", "orcid": "0000-0002-4697-798X", "researcher": {"href": "https://publications.scilifelab.se/researcher/263b14bd385c42649b4f31a1fee009ce.json"}}, {"family": "Wang", "given": "Liang-Bo", "initials": "LB", "orcid": "0000-0001-6977-9348", "researcher": {"href": "https://publications.scilifelab.se/researcher/8c831d5f02f04d31a89688ba02316aa4.json"}}, {"family": "Dong", "given": "Guanlan", "initials": "G", "orcid": "0000-0002-4747-6036", "researcher": {"href": "https://publications.scilifelab.se/researcher/ad63b4954fc7483bb4eadc4ce7d5938c.json"}}, {"family": "Liang", "given": "Wen-Wei", "initials": "WW"}, {"family": "Weerasinghe", "given": "Amila", "initials": "A", "orcid": "0000-0003-3568-5823", "researcher": {"href": "https://publications.scilifelab.se/researcher/4cb7a3b0bd5641688178c1d84200f9e7.json"}}, {"family": "Li", "given": "Shantao", "initials": "S", "orcid": "0000-0002-5440-2780", "researcher": {"href": "https://publications.scilifelab.se/researcher/9204d1cf2cef4a068c4f0b8bffd4a371.json"}}, {"family": "Li", "given": "Yize", "initials": "Y"}, {"family": "Kelso", "given": "Sean", "initials": "S"}, {"family": "MC3 Working Group", "given": "", "initials": ""}, {"family": "PCAWG novel somatic mutation calling methods working group", "given": "", "initials": ""}, {"family": "Saksena", "given": "Gordon", "initials": "G", "orcid": "0000-0001-6630-7935", "researcher": {"href": "https://publications.scilifelab.se/researcher/9acc7eddfc5047cfb0972de9134e2ad8.json"}}, {"family": "Ellrott", "given": "Kyle", "initials": "K", "orcid": "0000-0002-6573-5900", "researcher": {"href": "https://publications.scilifelab.se/researcher/35d682f015af4da3bff3b13cfd6f3f91.json"}}, {"family": "Wendl", "given": "Michael C", "initials": "MC"}, {"family": "Wheeler", "given": "David A", "initials": "DA", "orcid": "0000-0002-9056-6299", "researcher": {"href": "https://publications.scilifelab.se/researcher/13d586dd710f4452a76af607baeb219f.json"}}, {"family": "Getz", "given": "Gad", "initials": "G", "orcid": "0000-0002-0936-0753", "researcher": {"href": "https://publications.scilifelab.se/researcher/974b292190aa40c4a3b0c1d7ab735376.json"}}, {"family": "Simpson", "given": "Jared T", "initials": "JT"}, {"family": "Gerstein", "given": "Mark B", "initials": "MB", "orcid": "0000-0002-9746-3719", "researcher": {"href": "https://publications.scilifelab.se/researcher/345c9cc52dae493595c1d9ce10c0891d.json"}}, {"family": "Ding", "given": "Li", "initials": "L"}, {"family": "PCAWG Consortium", "given": "", "initials": ""}], "type": "comparative study", "published": "2020-09-21", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "11", "issue": "1", "pages": "4748", "issn-l": "2041-1723"}, "abstract": "The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts.", "doi": "10.1038/s41467-020-18151-y", "pmid": "32958763", "labels": {"Clinical Genomics Uppsala": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-18151-y"}, {"db": "pmc", "key": "PMC7505971"}], "notes": [], "created": "2020-12-10T14:46:47.966Z", "modified": "2021-11-10T12:47:09.115Z"}, {"entity": "publication", "iuid": "5efb2fa83f7f42c18ee609f625619eeb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5efb2fa83f7f42c18ee609f625619eeb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5efb2fa83f7f42c18ee609f625619eeb"}}, "title": "Generation of Sequencing Libraries for Structural Analysis of Bacterial 5' UTRs.", "authors": [{"family": "Ignatov", "given": "Dmitriy", "initials": "D"}, {"family": "Vaitkevicius", "given": "Karolis", "initials": "K"}, {"family": "Johansson", "given": "J\u00f6rgen", "initials": "J"}], "type": "journal article", "published": "2020-09-18", "journal": {"title": "STAR Protoc", "issn": "2666-1667", "volume": "1", "issue": "2", "pages": "100046", "issn-l": null}, "abstract": "The structure of 5' untranslated regions (5' UTRs) of bacterial mRNAs often determines the fate of the transcripts. Using a dimethyl sulfate mutational profiling with sequencing (DMS-MaPseq) approach, we developed a protocol to generate sequence libraries to determine the base-pairing status of adenines and cytosines in the 5' UTRs of bacterial mRNAs. Our method increases the sequencing depth of the 5' UTRs and allows detection of changes in their structures by sequencing libraries of moderate sizes. For complete details on the use and execution of this protocol, please refer to Ignatov et al. (2020).", "doi": "10.1016/j.xpro.2020.100046", "pmid": "33111092", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S2666-1667(20)30033-2"}, {"db": "pmc", "key": "PMC7580233"}], "notes": [], "created": "2020-12-07T16:38:29.482Z", "modified": "2024-01-16T13:48:41.708Z"}, {"entity": "publication", "iuid": "c61c5e3bfa1f45f0b6deccba8623d717", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c61c5e3bfa1f45f0b6deccba8623d717.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c61c5e3bfa1f45f0b6deccba8623d717"}}, "title": "Parvimonas micra as a putative non-invasive faecal biomarker for colorectal cancer.", "authors": [{"family": "L\u00f6wenmark", "given": "Thyra", "initials": "T"}, {"family": "L\u00f6fgren-Burstr\u00f6m", "given": "Anna", "initials": "A"}, {"family": "Zingmark", "given": "Carl", "initials": "C"}, {"family": "Ekl\u00f6f", "given": "Vincy", "initials": "V"}, {"family": "Dahlberg", "given": "Michael", "initials": "M"}, {"family": "Wai", "given": "Sun Nyunt", "initials": "SN"}, {"family": "Larsson", "given": "P\u00e4r", "initials": "P", "orcid": "0000-0001-9054-5191", "researcher": {"href": "https://publications.scilifelab.se/researcher/573c6350305a49cba2ac0798dea21ae0.json"}}, {"family": "Ljuslinder", "given": "Ingrid", "initials": "I"}, {"family": "Edin", "given": "Sofia", "initials": "S"}, {"family": "Palmqvist", "given": "Richard", "initials": "R", "orcid": "0000-0002-9933-2843", "researcher": {"href": "https://publications.scilifelab.se/researcher/40ae823e5364458b8f957a65a82c741f.json"}}], "type": "journal article", "published": "2020-09-17", "journal": {"title": "Sci Rep", "issn": "2045-2322", "issn-l": "2045-2322", "volume": "10", "issue": "1", "pages": "15250"}, "abstract": "The use of faecal microbial markers as non-invasive biomarkers for colorectal cancer (CRC) has been suggested, but not fully elucidated. Here, we have evaluated the importance of Parvimonas micra as a potential non-invasive faecal biomarker in CRC and its relation to other microbial biomarkers. The levels of P. micra, F. nucleatum and clbA + bacteria were quantified using qPCR in faecal samples from a population-based cohort of patients undergoing colonoscopy due to symptoms from the large bowel. The study included 38 CRC patients, 128 patients with dysplasia and 63 controls. The results were validated in a second consecutive CRC cohort including faecal samples from 238 CRC patients and 94 controls. We found significantly higher levels of P. micra in faecal samples from CRC patients compared to controls. A test for P. micra could detect CRC with a specificity of 87.3% and a sensitivity of 60.5%. In addition, we found that combining P. micra with other microbial markers, could further enhance test sensitivity. Our findings support the potential use of P. micra as a non-invasive biomarker for CRC. Together with other microbial faecal markers, P. micra may identify patients with \"high risk\" microbial patterns, indicating increased risk and incidence of cancer.", "doi": "10.1038/s41598-020-72132-1", "pmid": "32943695", "labels": {"Clinical Genomics Ume\u00e5": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-72132-1"}, {"db": "pmc", "key": "PMC7499209"}], "notes": [], "created": "2021-06-18T12:03:49.145Z", "modified": "2021-12-08T14:18:07.401Z"}, {"entity": "publication", "iuid": "83bfe5d1d31a4dd282c21d70ba3a05f7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/83bfe5d1d31a4dd282c21d70ba3a05f7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/83bfe5d1d31a4dd282c21d70ba3a05f7"}}, "title": "Macrocyclization of bis-indole quinolines for selective stabilization of G-quadruplex DNA structures.", "authors": [{"family": "Das", "given": "Rabindra Nath", "initials": "RN", "orcid": "0000-0001-6347-2169", "researcher": {"href": "https://publications.scilifelab.se/researcher/fec8d8bcbe8648258cfbab86693c77c6.json"}}, {"family": "Andr\u00e9asson", "given": "M\u00e5ns", "initials": "M", "orcid": "0000-0001-8089-2333", "researcher": {"href": "https://publications.scilifelab.se/researcher/7345c9c952d84801ad8334e3742ab7ec.json"}}, {"family": "Kumar", "given": "Rajendra", "initials": "R", "orcid": "0000-0002-7268-9519", "researcher": {"href": "https://publications.scilifelab.se/researcher/4ba57d44c650444aa51a030541d3bba7.json"}}, {"family": "Chorell", "given": "Erik", "initials": "E", "orcid": "0000-0003-2523-1940", "researcher": {"href": "https://publications.scilifelab.se/researcher/ada783ae0a824621a3b8e1024aae13a4.json"}}], "type": "journal article", "published": "2020-09-16", "journal": {"title": "Chem. Sci.", "issn": "2041-6520", "volume": "11", "issue": "38", "pages": "10529-10537", "issn-l": null}, "abstract": "The recognition of G-quadruplex (G4) DNA structures as important regulatory elements in biological mechanisms, and the connection between G4s and the evolvement of different diseases, has sparked interest in developing small organic molecules targeting G4s. However, such compounds often lack drug-like properties and selectivity. Here, we describe the design and synthesis of a novel class of macrocyclic bis-indole quinolines based on their non-macrocyclic lead compounds. The effects of the macrocyclization on the ability to interact with G4 DNA structures were investigated using biophysical assays and molecular dynamic simulations. Overall, this revealed compounds with potent abilities to interact with and stabilize G4 structures and a clear selectivity for both G4 DNA over dsDNA and for parallel/hybrid G4 topologies, which could be attributed to the macrocyclic structure. Moreover, we obtained knowledge about the structure-activity relationship of importance for the macrocyclic design and how structural modifications could be made to construct improved macrocyclic compounds. Thus, the macrocyclization of G4 ligands can serve as a basis for the optimization of research tools to study G4 biology and potential therapeutics targeting G4-related diseases.", "doi": "10.1039/d0sc03519j", "pmid": "34094311", "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [{"db": "pii", "key": "d0sc03519j"}, {"db": "pmc", "key": "PMC8162405"}], "notes": [], "created": "2020-11-24T20:27:43.691Z", "modified": "2025-10-17T13:03:56.637Z"}, {"entity": "publication", "iuid": "b0d422e67e22439cba7da9453032ef86", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b0d422e67e22439cba7da9453032ef86.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b0d422e67e22439cba7da9453032ef86"}}, "title": "Presynaptic dysfunction in CASK-related neurodevelopmental disorders.", "authors": [{"family": "Becker", "given": "Martin", "initials": "M", "orcid": "0000-0001-8442-4246", "researcher": {"href": "https://publications.scilifelab.se/researcher/85eaa4173364473d83506125206a7193.json"}}, {"family": "Mastropasqua", "given": "Francesca", "initials": "F"}, {"family": "Reising", "given": "Jan Philipp", "initials": "JP"}, {"family": "Maier", "given": "Simon", "initials": "S"}, {"family": "Ho", "given": "Mai-Lan", "initials": "ML"}, {"family": "Rabkina", "given": "Ielyzaveta", "initials": "I"}, {"family": "Li", "given": "Danyang", "initials": "D"}, {"family": "Neufeld", "given": "Janina", "initials": "J", "orcid": "0000-0002-7743-526X", "researcher": {"href": "https://publications.scilifelab.se/researcher/c82ade7791b24c46818bbef76984a383.json"}}, {"family": "Ballenberger", "given": "Lea", "initials": "L"}, {"family": "Myers", "given": "Lynnea", "initials": "L"}, {"family": "Moritz", "given": "Viveka", "initials": "V"}, {"family": "Kele", "given": "Malin", "initials": "M"}, {"family": "Wincent", "given": "Josephine", "initials": "J"}, {"family": "Willfors", "given": "Charlotte", "initials": "C"}, {"family": "Sitnikov", "given": "Rouslan", "initials": "R"}, {"family": "Herlenius", "given": "Eric", "initials": "E", "orcid": "0000-0002-6859-0620", "researcher": {"href": "https://publications.scilifelab.se/researcher/9d634beec270431a8805e609554ce1c9.json"}}, {"family": "Anderlid", "given": "Britt-Marie", "initials": "BM"}, {"family": "Falk", "given": "Anna", "initials": "A", "orcid": "0000-0003-1634-8610", "researcher": {"href": "https://publications.scilifelab.se/researcher/8b708dfb7f0548589bdee53d6e6b536e.json"}}, {"family": "B\u00f6lte", "given": "Sven", "initials": "S", "orcid": "0000-0002-4579-4970", "researcher": {"href": "https://publications.scilifelab.se/researcher/bead50319cae447f90bcf7658d9edf56.json"}}, {"family": "Tammimies", "given": "Kristiina", "initials": "K", "orcid": "0000-0002-8324-4697", "researcher": {"href": "https://publications.scilifelab.se/researcher/ba19ec07147743c6942ea10c9a92482a.json"}}], "type": "journal article", "published": "2020-09-14", "journal": {"title": "Transl Psychiatry", "issn": "2158-3188", "issn-l": "2158-3188", "volume": "10", "issue": "1", "pages": "312"}, "abstract": "CASK-related disorders are genetically defined neurodevelopmental syndromes. There is limited information about the effects of CASK mutations in human neurons. Therefore, we sought to delineate CASK-mutation consequences and neuronal effects using induced pluripotent stem cell-derived neurons from two mutation carriers. One male case with autism spectrum disorder carried a novel splice-site mutation and a female case with intellectual disability carried an intragenic tandem duplication. We show reduction of CASK protein in maturing neurons from the mutation carriers, which leads to significant downregulation of genes involved in presynaptic development and of CASK protein interactors. Furthermore, CASK-deficient neurons showed decreased inhibitory presynapse size as indicated by VGAT staining, which may alter the excitatory-inhibitory (E/I) balance in developing neural circuitries. Using in vivo magnetic resonance spectroscopy quantification of GABA in the male mutation carrier, we further highlight the possibility to validate in vitro cellular data in the brain. Our data show that future pharmacological and clinical studies on targeting presynapses and E/I imbalance could lead to specific treatments for CASK-related disorders.", "doi": "10.1038/s41398-020-00994-0", "pmid": "32929080", "labels": {"Eukaryotic Single Cell Genomics (ESCG)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41398-020-00994-0"}, {"db": "pmc", "key": "PMC7490425"}], "notes": [], "created": "2021-01-11T13:13:34.637Z", "modified": "2024-01-16T13:48:41.715Z"}, {"entity": "publication", "iuid": "3cdb55a424e240c89126260f60182ab5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3cdb55a424e240c89126260f60182ab5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3cdb55a424e240c89126260f60182ab5"}}, "title": "Diversity and Abundance of Microbial Communities in UASB Reactors during Methane Production from Hydrolyzed Wheat Straw and Lucerne.", "authors": [{"family": "Liu", "given": "Tong", "initials": "T", "orcid": "0000-0002-6456-4767", "researcher": {"href": "https://publications.scilifelab.se/researcher/1deea3cff23c4ae98c971c82f013ef45.json"}}, {"family": "Schn\u00fcrer", "given": "Anna", "initials": "A", "orcid": "0000-0003-0038-553X", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f81992bc8ed48318f8197fc8caabb4f.json"}}, {"family": "Bj\u00f6rkmalm", "given": "Johanna", "initials": "J"}, {"family": "Willquist", "given": "Karin", "initials": "K"}, {"family": "Kreuger", "given": "Emma", "initials": "E", "orcid": "0000-0002-7797-8854", "researcher": {"href": "https://publications.scilifelab.se/researcher/d7467affb7384af2b78e9a74efbd9c86.json"}}], "type": "journal article", "published": "2020-09-11", "journal": {"title": "Microorganisms", "issn": "2076-2607", "volume": "8", "issue": "9", "pages": "1394", "issn-l": "2076-2607"}, "abstract": "The use of straw for biofuel production is encouraged by the European Union. A previous study showed the feasibility of producing biomethane in upflow anaerobic sludge blanket (UASB) reactors using hydrolyzed, steam-pretreated wheat straw, before and after dark fermentation with Caldicellulosiruptor saccharolyticus, and lucerne. This study provides information on overall microbial community development in those UASB processes and changes related to acidification. The bacterial and archaeal community in granular samples was analyzed using high-throughput amplicon sequencing. Anaerobic digestion model no. 1 (ADM1) was used to predict the abundance of microbial functional groups. The sequencing results showed decreased richness and diversity in the microbial community, and decreased relative abundance of bacteria in relation to archaea, after process acidification. Canonical correspondence analysis showed significant negative correlations between the concentration of organic acids and three phyla, and positive correlations with seven phyla. Organic loading rate and total COD fed also showed significant correlations with microbial community structure, which changed over time. ADM1 predicted a decrease in acetate degraders after a decrease to pH \u2264 6.5. Acidification had a sustained effect on the microbial community and process performance.", "doi": "10.3390/microorganisms8091394", "pmid": "32932830", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "microorganisms8091394"}, {"db": "pmc", "key": "PMC7565072"}], "notes": [], "created": "2020-12-08T23:46:54.290Z", "modified": "2024-01-16T13:48:41.725Z"}, {"entity": "publication", "iuid": "0a4b469382934005bf79f0c29264def6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0a4b469382934005bf79f0c29264def6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0a4b469382934005bf79f0c29264def6"}}, "title": "Compositional and functional differences of the mucosal microbiota along the intestine of healthy individuals.", "authors": [{"family": "Vaga", "given": "Stefania", "initials": "S"}, {"family": "Lee", "given": "Sunjae", "initials": "S"}, {"family": "Ji", "given": "Boyang", "initials": "B"}, {"family": "Andreasson", "given": "Anna", "initials": "A"}, {"family": "Talley", "given": "Nicholas J", "initials": "NJ"}, {"family": "Agr\u00e9us", "given": "Lars", "initials": "L"}, {"family": "Bidkhori", "given": "Gholamreza", "initials": "G"}, {"family": "Kovatcheva-Datchary", "given": "Petia", "initials": "P"}, {"family": "Park", "given": "Junseok", "initials": "J"}, {"family": "Lee", "given": "Doheon", "initials": "D"}, {"family": "Proctor", "given": "Gordon", "initials": "G"}, {"family": "Ehrlich", "given": "Stanislav Dusko", "initials": "SD"}, {"family": "Nielsen", "given": "Jens", "initials": "J", "orcid": "0000-0002-9955-6003", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a596e289be4438a8a2653b1f25fea8b.json"}}, {"family": "Engstrand", "given": "Lars", "initials": "L"}, {"family": "Shoaie", "given": "Saeed", "initials": "S"}], "type": "clinical trial", "published": "2020-09-11", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "14977", "issn-l": "2045-2322"}, "abstract": "Gut mucosal microbes evolved closest to the host, developing specialized local communities. There is, however, insufficient knowledge of these communities as most studies have employed sequencing technologies to investigate faecal microbiota only. This work used shotgun metagenomics of mucosal biopsies to explore the microbial communities' compositions of terminal ileum and large intestine in 5 healthy individuals. Functional annotations and genome-scale metabolic modelling of selected species were then employed to identify local functional enrichments. While faecal metagenomics provided a good approximation of the average gut mucosal microbiome composition, mucosal biopsies allowed detecting the subtle variations of local microbial communities. Given their significant enrichment in the mucosal microbiota, we highlight the roles of Bacteroides species and describe the antimicrobial resistance biogeography along the intestine. We also detail which species, at which locations, are involved with the tryptophan/indole pathway, whose malfunctioning has been linked to pathologies including inflammatory bowel disease. Our study thus provides invaluable resources for investigating mechanisms connecting gut microbiota and host pathophysiology.", "doi": "10.1038/s41598-020-71939-2", "pmid": "32917913", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-71939-2"}, {"db": "pmc", "key": "PMC7486370"}], "notes": [], "created": "2020-12-07T16:28:54.238Z", "modified": "2024-01-16T13:48:41.733Z"}, {"entity": "publication", "iuid": "946798060ff74dd29d4437469e57b3d1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/946798060ff74dd29d4437469e57b3d1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/946798060ff74dd29d4437469e57b3d1"}}, "title": "A whole-genome sequenced control population in northern Sweden reveals subregional genetic differences.", "authors": [{"family": "Svensson", "given": "Daniel", "initials": "D", "orcid": "0000-0002-4476-9255", "researcher": {"href": "https://publications.scilifelab.se/researcher/75bc51f60237478abec1fb2969abc873.json"}}, {"family": "Rentoft", "given": "Matilda", "initials": "M"}, {"family": "Dahlin", "given": "Anna M", "initials": "AM"}, {"family": "Lundholm", "given": "Emma", "initials": "E"}, {"family": "Olason", "given": "Pall I", "initials": "PI"}, {"family": "Sj\u00f6din", "given": "Andreas", "initials": "A", "orcid": "0000-0001-5350-4219", "researcher": {"href": "https://publications.scilifelab.se/researcher/6398d7c06a414ea6bcaf2579a8587452.json"}}, {"family": "Nylander", "given": "Carin", "initials": "C"}, {"family": "Melin", "given": "Beatrice S", "initials": "BS"}, {"family": "Trygg", "given": "Johan", "initials": "J", "orcid": "0000-0003-3799-6094", "researcher": {"href": "https://publications.scilifelab.se/researcher/7df02186ac1a4a60952737b1690363b7.json"}}, {"family": "Johansson", "given": "Erik", "initials": "E", "orcid": "0000-0002-8526-6224", "researcher": {"href": "https://publications.scilifelab.se/researcher/3503f87335764d4185fade92739855e9.json"}}], "type": "journal article", "published": "2020-09-11", "journal": {"title": "PLoS ONE", "issn": "1932-6203", "volume": "15", "issue": "9", "pages": "e0237721", "issn-l": "1932-6203"}, "abstract": "The number of national reference populations that are whole-genome sequenced are rapidly increasing. Partly driving this development is the fact that genetic disease studies benefit from knowing the genetic variation typical for the geographical area of interest. A whole-genome sequenced Swedish national reference population (n = 1000) has been recently published but with few samples from northern Sweden. In the present study we have whole-genome sequenced a control population (n = 300) (ACpop) from V\u00e4sterbotten County, a sparsely populated region in northern Sweden previously shown to be genetically different from southern Sweden. The aggregated variant frequencies within ACpop are publicly available (DOI 10.17044/NBIS/G000005) to function as a basic resource in clinical genetics and for genetic studies. Our analysis of ACpop, representing approximately 0.11% of the population in V\u00e4sterbotten, indicates the presence of a genetic substructure within the county. Furthermore, a demographic analysis showed that the population from which samples were drawn was to a large extent geographically stationary, a finding that was corroborated in the genetic analysis down to the level of municipalities. Including ACpop in the reference population when imputing unknown variants in a V\u00e4sterbotten cohort resulted in a strong increase in the number of high-confidence imputed variants (up to 81% for variants with minor allele frequency < 5%). ACpop was initially designed for cancer disease studies, but the genetic structure within the cohort will be of general interest for all genetic disease studies in northern Sweden.", "doi": "10.1371/journal.pone.0237721", "pmid": "32915809", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "PONE-D-20-06062"}, {"db": "pmc", "key": "PMC7485808"}], "notes": [], "created": "2020-12-08T23:48:26.250Z", "modified": "2024-01-16T13:48:41.742Z"}, {"entity": "publication", "iuid": "48a454b337234b679147081013a4d06c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/48a454b337234b679147081013a4d06c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/48a454b337234b679147081013a4d06c"}}, "title": "Complete Genome Sequence of Francisella halioticida Type Strain DSM 23729 (FSC1005).", "authors": [{"family": "Uneklint", "given": "Ingrid", "initials": "I"}, {"family": "\u00d6hrman", "given": "Caroline", "initials": "C", "orcid": "0000-0001-8489-757X", "researcher": {"href": "https://publications.scilifelab.se/researcher/804b654aa0be4d7a9ecdf113487fe443.json"}}, {"family": "Karlsson", "given": "Linda", "initials": "L"}, {"family": "Bystr\u00f6m", "given": "Mona", "initials": "M"}, {"family": "H\u00e4gglund", "given": "Emil", "initials": "E"}, {"family": "Forsman", "given": "Mats", "initials": "M"}, {"family": "Sj\u00f6din", "given": "Andreas", "initials": "A", "orcid": "0000-0001-5350-4219", "researcher": {"href": "https://publications.scilifelab.se/researcher/6398d7c06a414ea6bcaf2579a8587452.json"}}], "type": "journal article", "published": "2020-09-10", "journal": {"title": "Microbiol Resour Announc", "issn": "2576-098X", "volume": "9", "issue": "37", "pages": null, "issn-l": "2576-098X"}, "abstract": "Here, we announce the complete genome sequence of the Francisella halioticida type strain DSM 23729 (FSC1005), isolated from a diseased cultured giant abalone in Japan in 2005. The genome is composed of a 2,197,430-bp-long circular chromosome, with a G+C content of 31.2%.", "doi": "10.1128/MRA.00541-20", "pmid": "32912905", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pii", "key": "9/37/e00541-20"}, {"db": "pmc", "key": "PMC7484064"}], "notes": [], "created": "2020-09-15T06:07:36.536Z", "modified": "2021-11-10T12:47:21.455Z"}, {"entity": "publication", "iuid": "043ab27fa61944e99a7e279442373b57", "links": {"self": {"href": "https://publications.scilifelab.se/publication/043ab27fa61944e99a7e279442373b57.json"}, "display": {"href": "https://publications.scilifelab.se/publication/043ab27fa61944e99a7e279442373b57"}}, "title": "Integration of molecular profiles in a longitudinal wellness profiling cohort.", "authors": [{"family": "Tebani", "given": "Abdellah", "initials": "A"}, {"family": "Gummesson", "given": "Anders", "initials": "A", "orcid": "0000-0003-0024-960X", "researcher": {"href": "https://publications.scilifelab.se/researcher/cb164de27f2846328bb675876922a5fe.json"}}, {"family": "Zhong", "given": "Wen", "initials": "W", "orcid": "0000-0002-7422-6104", "researcher": {"href": "https://publications.scilifelab.se/researcher/a82c3b7da3b8472392d39ca5f6d5bedb.json"}}, {"family": "Koistinen", "given": "Ina Schuppe", "initials": "IS"}, {"family": "Lakshmikanth", "given": "Tadepally", "initials": "T", "orcid": "0000-0001-7256-5770", "researcher": {"href": "https://publications.scilifelab.se/researcher/92e81aa6b0cf4ff0a18b14098bf0fcc1.json"}}, {"family": "Olsson", "given": "Lisa M", "initials": "LM", "orcid": "0000-0001-9730-1915", "researcher": {"href": "https://publications.scilifelab.se/researcher/2460963d77ee4eee9409fbd8c257d910.json"}}, {"family": "Boulund", "given": "Fredrik", "initials": "F", "orcid": "0000-0002-3806-323X", "researcher": {"href": "https://publications.scilifelab.se/researcher/514fbe8cab5e4f25afa33fcd3e0523b5.json"}}, {"family": "Neiman", "given": "Maja", "initials": "M"}, {"family": "Stenlund", "given": "Hans", "initials": "H"}, {"family": "Hellstr\u00f6m", "given": "Cecilia", "initials": "C", "orcid": "0000-0003-0880-5375", "researcher": {"href": "https://publications.scilifelab.se/researcher/dbf3f75938f0442a9b1ae5c98565f44a.json"}}, {"family": "Karlsson", "given": "Max J", "initials": "MJ", "orcid": "0000-0002-7000-4416", "researcher": {"href": "https://publications.scilifelab.se/researcher/6e1bd9a99e5648c3998c6e0106a07fbc.json"}}, {"family": "Arif", "given": "Muhammad", "initials": "M", "orcid": "0000-0003-2261-0881", "researcher": {"href": "https://publications.scilifelab.se/researcher/fbe369c4e07c44c09dcf64a3c18d833e.json"}}, {"family": "Dodig-Crnkovi\u0107", "given": "Tea", "initials": "T", "orcid": "0000-0002-2875-896X", "researcher": {"href": "https://publications.scilifelab.se/researcher/cf18af5b676b449693945249fc1767e4.json"}}, {"family": "Mardinoglu", "given": "Adil", "initials": "A", "orcid": "0000-0002-4254-6090", "researcher": {"href": "https://publications.scilifelab.se/researcher/da756265658c4ed2a8911644583e07a3.json"}}, {"family": "Lee", "given": "Sunjae", "initials": "S"}, {"family": "Zhang", "given": "Cheng", "initials": "C", "orcid": "0000-0002-3721-8586", "researcher": {"href": "https://publications.scilifelab.se/researcher/d1b9559ac41749fa91c4025108947e13.json"}}, {"family": "Chen", "given": "Yang", "initials": "Y"}, {"family": "Olin", "given": "Axel", "initials": "A", "orcid": "0000-0002-1161-4476", "researcher": {"href": "https://publications.scilifelab.se/researcher/8dfb8efde80a4a508c93714729259aba.json"}}, {"family": "Mikes", "given": "Jaromir", "initials": "J", "orcid": "0000-0002-9941-7855", "researcher": {"href": "https://publications.scilifelab.se/researcher/21c127bffa7c4a01af7fad8ba6bac90b.json"}}, {"family": "Danielsson", "given": "Hanna", "initials": "H", "orcid": "0000-0001-6959-7704", "researcher": {"href": "https://publications.scilifelab.se/researcher/32e346ce0d514179baea3c97b615e665.json"}}, {"family": "von Feilitzen", "given": "Kalle", "initials": "K"}, {"family": "Jansson", "given": "Per-Anders", "initials": "PA"}, {"family": "Anger\u00e5s", "given": "Oskar", "initials": "O"}, {"family": "Huss", "given": "Mikael", "initials": "M"}, {"family": "Kjellqvist", "given": "Sanela", "initials": "S"}, {"family": "Odeberg", "given": "Jacob", "initials": "J", "orcid": "0000-0003-0996-1644", "researcher": {"href": "https://publications.scilifelab.se/researcher/d1f04395fea84d898a8fe2a9875e79c4.json"}}, {"family": "Edfors", "given": "Fredrik", "initials": "F", "orcid": "0000-0002-0017-7987", "researcher": {"href": "https://publications.scilifelab.se/researcher/3f0e8af0b9144bcd9fd566d316008a62.json"}}, {"family": "Tremaroli", "given": "Valentina", "initials": "V"}, {"family": "Forsstr\u00f6m", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Schwenk", "given": "Jochen M", "initials": "JM", "orcid": "0000-0001-8141-8449", "researcher": {"href": "https://publications.scilifelab.se/researcher/aba5822711b246b397fffacb7ae403b3.json"}}, {"family": "Nilsson", "given": "Peter", "initials": "P", "orcid": "0000-0002-4657-8532", "researcher": {"href": "https://publications.scilifelab.se/researcher/799bcf1cf8cf451296f4535dd4ca9dc0.json"}}, {"family": "Moritz", "given": "Thomas", "initials": "T", "orcid": "0000-0002-4258-3190", "researcher": {"href": "https://publications.scilifelab.se/researcher/95ad5b7fe48f42eda1328f54a385e097.json"}}, {"family": "B\u00e4ckhed", "given": "Fredrik", "initials": "F", "orcid": "0000-0002-4871-8818", "researcher": {"href": "https://publications.scilifelab.se/researcher/1689878e0c5542d08d3e2d5043a6ce5c.json"}}, {"family": "Engstrand", "given": "Lars", "initials": "L"}, {"family": "Brodin", "given": "Petter", "initials": "P", "orcid": "0000-0002-8103-0046", "researcher": {"href": "https://publications.scilifelab.se/researcher/40097353cdb24e52bf2330eb687042bf.json"}}, {"family": "Bergstr\u00f6m", "given": "G\u00f6ran", "initials": "G", "orcid": "0000-0003-4289-5722", "researcher": {"href": "https://publications.scilifelab.se/researcher/fbc3ade3079e4265ad42ed1be485bc24.json"}}, {"family": "Uhlen", "given": "Mathias", "initials": "M", "orcid": "0000-0002-4858-8056", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff81da3cb0cf4262873b993a1b06798c.json"}}, {"family": "Fagerberg", "given": "Linn", "initials": "L", "orcid": "0000-0003-0198-7137", "researcher": {"href": "https://publications.scilifelab.se/researcher/e8db0663a10a4d9e9241457609d5952e.json"}}], "type": "journal article", "published": "2020-09-08", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "11", "issue": "1", "pages": "4487"}, "abstract": "An important aspect of precision medicine is to probe the stability in molecular profiles among healthy individuals over time. Here, we sample a longitudinal wellness cohort with 100 healthy individuals and analyze blood molecular profiles including proteomics, transcriptomics, lipidomics, metabolomics, autoantibodies and immune cell profiling, complemented with gut microbiota composition and routine clinical chemistry. Overall, our results show high variation between individuals across different molecular readouts, while the intra-individual baseline variation is low. The analyses show that each individual has a unique and stable plasma protein profile throughout the study period and that many individuals also show distinct profiles with regards to the other omics datasets, with strong underlying connections between the blood proteome and the clinical chemistry parameters. In conclusion, the results support an individual-based definition of health and show that comprehensive omics profiling in a longitudinal manner is a path forward for precision medicine.", "doi": "10.1038/s41467-020-18148-7", "pmid": "32900998", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "Autoimmunity and Serology Profiling": "Collaborative", "Affinity Proteomics Stockholm": "Collaborative", "Cellular Immunomonitoring": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative", "Swedish Metabolomics Centre": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-18148-7"}, {"db": "pmc", "key": "PMC7479148"}], "notes": [], "created": "2020-09-10T05:17:29.818Z", "modified": "2025-10-17T13:03:16.662Z"}, {"entity": "publication", "iuid": "6aea5c20a9e349c5b122a112cf62160d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6aea5c20a9e349c5b122a112cf62160d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6aea5c20a9e349c5b122a112cf62160d"}}, "title": "Profiling of Inflammatory Proteins in Plasma of HIV-1-Infected Children Receiving Antiretroviral Therapy.", "authors": [{"family": "Lemma", "given": "Mahlet", "initials": "M"}, {"family": "Petkov", "given": "Stefan", "initials": "S", "orcid": "0000-0002-8052-9646", "researcher": {"href": "https://publications.scilifelab.se/researcher/1c9fba3bf1ab4f60beac9bc5581f12f6.json"}}, {"family": "Bekele", "given": "Yonas", "initials": "Y"}, {"family": "Petros", "given": "Beyene", "initials": "B"}, {"family": "Howe", "given": "Rawleigh", "initials": "R"}, {"family": "Chiodi", "given": "Francesca", "initials": "F"}], "type": "journal article", "published": "2020-09-07", "journal": {"title": "Proteomes", "issn": "2227-7382", "volume": "8", "issue": "3", "pages": "24", "issn-l": "2227-7382"}, "abstract": "Treatment of HIV-1-infected patients results in improved clinical and immunological conditions, but severe non-AIDS-related conditions still persist. Novel proteomic platforms have identified inflammatory proteins where abundance is dysregulated in adult treated patients, whereas limited data are available in treated HIV-1 infection of children. Using a proteomic plasma profiling approach comprising 92 inflammation-related molecules, we analyzed specimens from 43 vertically HIV-1-infected children receiving antiretroviral treatment (ART) and matched controls in Ethiopia. The infected children were analyzed as a group and separately, according to age of treatment initiation. Proteins displaying a significantly different abundance between groups were hierarchically clustered and presented in heat maps. Random forest analysis was performed to pin-point proteins discriminating between groups; five proteins (STAMBP, CD5, TFG-\u03b1, TRANCE, AXIN1) were the strongest prediction factors for treated HIV-1 infection. TRANCE was previously linked to reduced bone mass levels in HIV-1-infected children. CCL4 chemokine, ligand to HIV-1 co-receptor CCR5, was the most critical protein for successful classification between children who initiated ART at different time points. Our data provide evidence that a dysregulated expression of proteins linked to immunological abnormalities and bone metabolism can be found in HIV-1-infected children with prolonged exposure to ART.", "doi": "10.3390/proteomes8030024", "pmid": "32906648", "labels": {"Affinity Proteomics Stockholm": "Service"}, "xrefs": [{"db": "pii", "key": "proteomes8030024"}, {"db": "pmc", "key": "PMC7563605"}], "notes": [], "created": "2020-12-10T16:30:02.494Z", "modified": "2021-11-10T12:47:23.760Z"}, {"entity": "publication", "iuid": "f0dc43b7323e459ca55148bf15d20642", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f0dc43b7323e459ca55148bf15d20642.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f0dc43b7323e459ca55148bf15d20642"}}, "title": "Genome sequence of segmented filamentous bacteria present in the human intestine.", "authors": [{"family": "Jonsson", "given": "Hans", "initials": "H"}, {"family": "Hugerth", "given": "Luisa W", "initials": "LW", "orcid": "0000-0001-5432-1764", "researcher": {"href": "https://publications.scilifelab.se/researcher/5dfdcf0109a942228d35d8dbfdede585.json"}}, {"family": "Sundh", "given": "John", "initials": "J"}, {"family": "Lundin", "given": "Eva", "initials": "E"}, {"family": "Andersson", "given": "Anders F", "initials": "AF", "orcid": "0000-0002-3627-6899", "researcher": {"href": "https://publications.scilifelab.se/researcher/caa76ee4438d4b4aad386ba8a90448c2.json"}}], "type": "journal article", "published": "2020-09-04", "journal": {"title": "Commun Biol", "issn": "2399-3642", "volume": "3", "issue": "1", "pages": "485", "issn-l": "2399-3642"}, "abstract": "Segmented filamentous bacteria (SFB) are unique immune modulatory bacteria colonizing the small intestine of a variety of animals in a host-specific manner. SFB exhibit filamentous growth and attach to the host's intestinal epithelium, offering a physical route of interaction. SFB affect functions of the host immune system, among them IgA production and T-cell maturation. Until now, no human-specific SFB genome has been reported. Here, we report the metagenomic reconstruction of an SFB genome from a human ileostomy sample. Phylogenomic analysis clusters the genome with SFB genomes from mouse, rat and turkey, but the genome is genetically distinct, displaying 65-71% average amino acid identity to the others. By screening human faecal metagenomic datasets, we identified individuals carrying sequences identical to the new SFB genome. We thus conclude that a unique SFB variant exists in humans and foresee a renewed interest in the elucidation of SFB functionality in this environment.", "doi": "10.1038/s42003-020-01214-7", "pmid": "32887924", "labels": {"Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s42003-020-01214-7"}, {"db": "pmc", "key": "PMC7474095"}], "notes": [], "created": "2020-11-16T08:52:13.095Z", "modified": "2024-01-16T13:48:41.758Z"}, {"entity": "publication", "iuid": "df0ebcff7ad2473fb0152621838de472", "links": {"self": {"href": "https://publications.scilifelab.se/publication/df0ebcff7ad2473fb0152621838de472.json"}, "display": {"href": "https://publications.scilifelab.se/publication/df0ebcff7ad2473fb0152621838de472"}}, "title": "An alpaca nanobody neutralizes SARS-CoV-2 by blocking receptor interaction.", "authors": [{"family": "Hanke", "given": "Leo", "initials": "L", "orcid": "0000-0001-5514-2418", "researcher": {"href": "https://publications.scilifelab.se/researcher/ece050a286f946f6807170cffc9320e7.json"}}, {"family": "Vidakovics Perez", "given": "Laura", "initials": "L", "orcid": "0000-0003-4283-812X", "researcher": {"href": "https://publications.scilifelab.se/researcher/8f8d317c1bf74fd5bfb3e63936f5ab5e.json"}}, {"family": "Sheward", "given": "Daniel J", "initials": "DJ"}, {"family": "Das", "given": "Hrishikesh", "initials": "H"}, {"family": "Schulte", "given": "Tim", "initials": "T"}, {"family": "Moliner-Morro", "given": "Ainhoa", "initials": "A"}, {"family": "Corcoran", "given": "Martin", "initials": "M"}, {"family": "Achour", "given": "Adnane", "initials": "A"}, {"family": "Karlsson Hedestam", "given": "Gunilla B", "initials": "GB"}, {"family": "H\u00e4llberg", "given": "B Martin", "initials": "BM", "orcid": "0000-0002-6781-0345", "researcher": {"href": "https://publications.scilifelab.se/researcher/2b7e4327d0ac48288afd6061f149156d.json"}}, {"family": "Murrell", "given": "Ben", "initials": "B", "orcid": "0000-0002-0393-4445", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a899203048943489bf7b6310a32b19f.json"}}, {"family": "McInerney", "given": "Gerald M", "initials": "GM", "orcid": "0000-0003-2257-7241", "researcher": {"href": "https://publications.scilifelab.se/researcher/5ac2f68095fe4426b97ec070865e5091.json"}}], "type": "journal article", "published": "2020-09-04", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "11", "issue": "1", "pages": "4420", "issn-l": "2041-1723"}, "abstract": "SARS-CoV-2 enters host cells through an interaction between the spike glycoprotein and the angiotensin converting enzyme 2 (ACE2) receptor. Directly preventing this interaction presents an attractive possibility for suppressing SARS-CoV-2 replication. Here, we report the isolation and characterization of an alpaca-derived single domain antibody fragment, Ty1, that specifically targets the receptor binding domain (RBD) of the SARS-CoV-2 spike, directly preventing ACE2 engagement. Ty1 binds the RBD with high affinity, occluding ACE2. A cryo-electron microscopy structure of the bound complex at 2.9 \u00c5 resolution reveals that Ty1 binds to an epitope on the RBD accessible in both the 'up' and 'down' conformations, sterically hindering RBD-ACE2 binding. While fusion to an Fc domain renders Ty1 extremely potent, Ty1 neutralizes SARS-CoV-2 spike pseudovirus as a 12.8 kDa nanobody, which can be expressed in high quantities in bacteria, presenting opportunities for manufacturing at scale. Ty1 is therefore an excellent candidate as an intervention against COVID-19.", "doi": "10.1038/s41467-020-18174-5", "pmid": "32887876", "labels": {"Protein Science Facility (PSF)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-18174-5"}, {"db": "pmc", "key": "PMC7473855"}], "notes": [], "created": "2020-09-08T08:44:04.841Z", "modified": "2024-01-16T13:48:41.765Z"}, {"entity": "publication", "iuid": "7402e0cb8efb4d9bbc6e8de14d1c1285", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7402e0cb8efb4d9bbc6e8de14d1c1285.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7402e0cb8efb4d9bbc6e8de14d1c1285"}}, "title": "Bilayer-Coated Nanoparticles Reveal How Influenza Viral Entry Depends on Membrane Deformability but Not Curvature.", "authors": [{"family": "Villamil Giraldo", "given": "Ana M", "initials": "AM"}, {"family": "Kasson", "given": "Peter M", "initials": "PM", "orcid": "0000-0002-3111-8103", "researcher": {"href": "https://publications.scilifelab.se/researcher/092334ac432b465a8401370e46eba935.json"}}], "type": "journal article", "published": "2020-09-03", "journal": {"title": "J Phys Chem Lett", "issn": "1948-7185", "volume": "11", "issue": "17", "pages": "7190-7196", "issn-l": "1948-7185"}, "abstract": "Enveloped viruses infect cells via fusion between the viral envelope and a cellular membrane. This membrane fusion process is driven by viral proteins, but slow stochastic protein activation dominates the fusion kinetics, making it challenging to probe the role of membrane mechanics in viral entry directly. Furthermore, many changes to the interacting membranes alter the curvature, deformability, and spatial organization of membranes simultaneously. We have used bilayer-coated silica nanoparticles to restrict the deformability of lipid membranes in a controllable manner. The single-event kinetics for fusion of influenza virus to coated nanoparticles permits independent testing of how the membrane curvature and deformability control the free energy barriers to fusion. Varying the free energy of membrane deformation, but not membrane curvature, causes a corresponding response in the fusion kinetics and fusion protein stoichiometry. Thus, the main free energy barrier to lipid mixing by influenza virus is controlled by membrane deformability and not the initial membrane curvature.", "doi": "10.1021/acs.jpclett.0c01778", "pmid": "32808796", "labels": {"Cryo-EM": "Service"}, "xrefs": [], "notes": [], "created": "2021-05-04T13:25:24.793Z", "modified": "2021-11-10T12:47:27.655Z"}, {"entity": "publication", "iuid": "f5196895ac8a4cebb5143f36ce3b1737", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f5196895ac8a4cebb5143f36ce3b1737.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f5196895ac8a4cebb5143f36ce3b1737"}}, "title": "Toward Two-Photon Absorbing Dyes with Unusually Potentiated Nonlinear Fluorescence Response.", "authors": [{"family": "Benitez-Martin", "given": "Carlos", "initials": "C", "orcid": "0000-0003-1821-9388", "researcher": {"href": "https://publications.scilifelab.se/researcher/d1fcdd6e053b462998fe7f463be60d96.json"}}, {"family": "Li", "given": "Shiming", "initials": "S"}, {"family": "Dominguez-Alfaro", "given": "Antonio", "initials": "A"}, {"family": "Najera", "given": "Francisco", "initials": "F", "orcid": "0000-0002-1635-5514", "researcher": {"href": "https://publications.scilifelab.se/researcher/59a60d855d794d45a9fff4746867037f.json"}}, {"family": "P\u00e9rez-Inestrosa", "given": "Ezequiel", "initials": "E", "orcid": "0000-0001-7546-5273", "researcher": {"href": "https://publications.scilifelab.se/researcher/5ecc62575cbc43d9bfb86efd8299499c.json"}}, {"family": "Pischel", "given": "Uwe", "initials": "U", "orcid": "0000-0001-8893-9829", "researcher": {"href": "https://publications.scilifelab.se/researcher/f834b537191b46659d27846e05238ef3.json"}}, {"family": "Andr\u00e9asson", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4695-7943", "researcher": {"href": "https://publications.scilifelab.se/researcher/28eb5affb5664c54be9171dfce6bea15.json"}}], "type": "journal article", "published": "2020-09-02", "journal": {"title": "J. Am. Chem. Soc.", "issn": "1520-5126", "volume": "142", "issue": "35", "pages": "14854-14858", "issn-l": "0002-7863"}, "abstract": "The combination of two two-photon-induced processes in a F\u00f6rster resonance energy transfer (FRET)-operated photochromic fluorene-dithienylethene dyad lays the foundation for the observation of a quartic dependence of the fluorescence signal on the excitation light intensity. While this photophysical behavior is predicted for a four-photon absorbing dye, the herein proposed approach opens the way to use two-photon absorbing dyes, reaching the same performance. Hence, the spatial resolution limit, being a critical parameter for applications in fluorescence imaging or data storage with common two-photon absorbing dyes, is dramatically improved.", "doi": "10.1021/jacs.0c07377", "pmid": "32799520", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7498150"}], "notes": [], "created": "2023-02-16T08:04:03.866Z", "modified": "2023-02-16T08:04:04.030Z"}, {"entity": "publication", "iuid": "f944b02e41bf428d8dfb2d7c6a8a8221", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f944b02e41bf428d8dfb2d7c6a8a8221.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f944b02e41bf428d8dfb2d7c6a8a8221"}}, "title": "River biofilms adapted to anthropogenic disturbances are more resistant to WWTP inputs.", "authors": [{"family": "Freixa", "given": "Anna", "initials": "A", "orcid": "0000-0003-1149-6526", "researcher": {"href": "https://publications.scilifelab.se/researcher/69bacfaa677d4e53afdcac4c46070093.json"}}, {"family": "Perujo", "given": "N\u00faria", "initials": "N"}, {"family": "Langenheder", "given": "Silke", "initials": "S"}, {"family": "Roman\u00ed", "given": "Anna M", "initials": "AM"}], "type": "journal article", "published": "2020-09-01", "journal": {"title": "FEMS Microbiol. Ecol.", "issn": "1574-6941", "issn-l": "0168-6496", "volume": "96", "issue": "9", "pages": null}, "abstract": "The sensitivity and spatial recovery of river sediment biofilms along 1 km after the input of two wastewater treatment plants (WWTPs) located in two river reaches with different degrees of anthropogenic influence were investigated. First, at the upper reach, we observed an inhibition of some microbial functions (microbial respiration and extracellular enzyme activities) and strong shifts in bacterial community composition (16S rRNA gene), whereas an increase in microbial biomass and activity and less pronounced effect on microbial diversity and community composition were seen at the lower reach. Second, at the lower reach we observed a quick spatial recovery (around 200 m downstream of the effluent) as most of the functions and community composition were similar to those from reference sites. On the other hand, bacterial community composition and water quality at the upper reach was still altered 1 km from the WWTP effluent. Our results indicate that biofilms in the upstream sites were more sensitive to the effect of WWTPs due to a lower degree of tolerance after a disturbance than communities located in more anthropogenically impacted sites.", "doi": "10.1093/femsec/fiaa152", "pmid": "32766791", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "5884858"}], "notes": [], "created": "2020-12-08T23:18:43.974Z", "modified": "2024-01-16T13:48:41.772Z"}, {"entity": "publication", "iuid": "89662d49b5714d43b2d4ee811777dd15", "links": {"self": {"href": "https://publications.scilifelab.se/publication/89662d49b5714d43b2d4ee811777dd15.json"}, "display": {"href": "https://publications.scilifelab.se/publication/89662d49b5714d43b2d4ee811777dd15"}}, "title": "Parallel Evolution of Bower-Building Behavior in Two Groups of Bowerbirds Suggested by Phylogenomics.", "authors": [{"family": "Ericson", "given": "Per G P", "initials": "PGP"}, {"family": "Irestedt", "given": "Martin", "initials": "M"}, {"family": "Nylander", "given": "Johan A A", "initials": "JAA"}, {"family": "Christidis", "given": "Les", "initials": "L"}, {"family": "Joseph", "given": "Leo", "initials": "L"}, {"family": "Qu", "given": "Yanhua", "initials": "Y"}], "type": "journal article", "published": "2020-09-01", "journal": {"title": "Syst. Biol.", "issn": "1076-836X", "volume": "69", "issue": "5", "pages": "820-829", "issn-l": "1063-5157"}, "abstract": "The bowerbirds in New Guinea and Australia include species that build the largest and perhaps most elaborately decorated constructions outside of humans. The males use these courtship bowers, along with their displays, to attract females. In these species, the mating system is polygynous and the females alone incubate and feed the nestlings. The bowerbirds also include 10 species of the socially monogamous catbirds in which the male participates in most aspects of raising the young. How the bower-building behavior evolved has remained poorly understood, as no comprehensive phylogeny exists for the family. It has been assumed that the monogamous catbird clade is sister to all polygynous species. We here test this hypothesis using a newly developed pipeline for obtaining homologous alignments of thousands of exonic and intronic regions from genomic data to build a phylogeny. Our well-supported species tree shows that the polygynous, bower-building species are not monophyletic. The result suggests either that bower-building behavior is an ancestral condition in the family that was secondarily lost in the catbirds, or that it has arisen in parallel in two lineages of bowerbirds. We favor the latter hypothesis based on an ancestral character reconstruction showing that polygyny but not bower-building is ancestral in bowerbirds, and on the observation that Scenopoeetes dentirostris, the sister species to one of the bower-building clades, does not build a proper bower but constructs a court for male display. This species is also sexually monomorphic in plumage despite having a polygynous mating system. We argue that the relatively stable tropical and subtropical forest environment in combination with low predator pressure and rich food access (mostly fruit) facilitated the evolution of these unique life-history traits. [Adaptive radiation; bowerbirds; mating system, sexual selection; whole genome sequencing.].", "doi": "10.1093/sysbio/syaa040", "pmid": "32415976", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "5838197"}, {"db": "pmc", "key": "PMC7440736"}], "notes": [], "created": "2020-07-08T13:05:12.870Z", "modified": "2024-01-16T13:48:41.780Z"}, {"entity": "publication", "iuid": "e47728c38b5d4015ac7f2d627f109b35", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e47728c38b5d4015ac7f2d627f109b35.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e47728c38b5d4015ac7f2d627f109b35"}}, "title": "Mutations Upstream of the TBX5 and PITX1 Transcription Factor Genes Are Associated with Feathered Legs in the Domestic Chicken.", "authors": [{"family": "Li", "given": "Jingyi", "initials": "J"}, {"family": "Lee", "given": "MiOk", "initials": "M"}, {"family": "Davis", "given": "Brian W", "initials": "BW"}, {"family": "Lamichhaney", "given": "Sangeet", "initials": "S"}, {"family": "Dorshorst", "given": "Ben J", "initials": "BJ"}, {"family": "Siegel", "given": "Paul B", "initials": "PB"}, {"family": "Andersson", "given": "Leif", "initials": "L"}], "type": "journal article", "published": "2020-09-01", "journal": {"title": "Mol. Biol. Evol.", "issn": "1537-1719", "volume": "37", "issue": "9", "pages": "2477-2486", "issn-l": "0737-4038"}, "abstract": "Feathered leg is a trait in domestic chickens that has undergone intense selection by fancy breeders. Previous studies have shown that two major loci controlling feathered leg are located on chromosomes 13 and 15. Here, we present genetic evidence for the identification of candidate causal mutations at these loci. This was accomplished by combining classical linkage mapping using an experimental cross segregating for feathered leg and high-resolution identical-by-descent mapping using whole-genome sequence data from 167 samples of chicken with or without feathered legs. The first predicted causal mutation is a single-base change located 25 kb upstream of the gene for the forelimb-specific transcription factor TBX5 on chromosome 15. The second is a 17.7-kb deletion located \u223c200 kb upstream of the gene for the hindlimb-specific transcription factor PITX1 on chromosome 13. These mutations are predicted to activate TBX5 and repress PITX1 expression, respectively. The study reveals a remarkable convergence in the evolution of the feathered-leg phenotype in domestic chickens and domestic pigeons, as this phenotype is caused by noncoding mutations upstream of the same two genes. Furthermore, the PITX1 causal variants are large overlapping deletions, 17.7 kb in chicken and 44 kb in pigeons. The results of the present study are consistent with the previously proposed model for pigeon that feathered leg is caused by reduced PITX1 expression and ectopic expression of TBX5 in hindlimb buds resulting in a shift of limb identity from hindlimb to more forelimb-like identity.", "doi": "10.1093/molbev/msaa093", "pmid": "32344431", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7475036"}, {"db": "pii", "key": "5818883"}], "notes": [], "created": "2020-09-15T07:09:20.506Z", "modified": "2023-06-19T11:50:20.480Z"}, {"entity": "publication", "iuid": "554b086169b84ddfbfcf49c9d41e38a1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/554b086169b84ddfbfcf49c9d41e38a1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/554b086169b84ddfbfcf49c9d41e38a1"}}, "title": "Evolutionary Remodeling of the Cell Envelope in Bacteria of the Planctomycetes Phylum.", "authors": [{"family": "Mahajan", "given": "Mayank", "initials": "M"}, {"family": "Seeger", "given": "Christian", "initials": "C"}, {"family": "Yee", "given": "Benjamin", "initials": "B"}, {"family": "Andersson", "given": "Siv G E", "initials": "SGE", "orcid": "0000-0003-0864-0259", "researcher": {"href": "https://publications.scilifelab.se/researcher/7884a5058383428ea3cbe7fc4505f36a.json"}}], "type": "journal article", "published": "2020-09-01", "journal": {"title": "Genome Biol Evol", "issn": "1759-6653", "issn-l": "1759-6653", "volume": "12", "issue": "9", "pages": "1528-1548"}, "abstract": "Bacteria of the Planctomycetes phylum have many unique cellular features, such as extensive membrane invaginations and the ability to import macromolecules. These features raise intriguing questions about the composition of their cell envelopes. In this study, we have used microscopy, phylogenomics, and proteomics to examine the composition and evolution of cell envelope proteins in Tuwongella immobilis and other members of the Planctomycetes. Cryo-electron tomography data indicated a distance of 45 nm between the inner and outer membranes in T. immobilis. Consistent with the wide periplasmic space, our bioinformatics studies showed that the periplasmic segments of outer-membrane proteins in type II secretion systems are extended in bacteria of the order Planctomycetales. Homologs of two highly abundant cysteine-rich cell wall proteins in T. immobilis were identified in all members of the Planctomycetales, whereas genes for peptidoglycan biosynthesis and cell elongation have been lost in many members of this bacterial group. The cell wall proteins contain multiple copies of the YTV motif, which is the only domain that is conserved and unique to the Planctomycetales. Earlier diverging taxa in the Planctomycetes phylum contain genes for peptidoglycan biosynthesis but no homologs to the YTV cell wall proteins. The major remodeling of the cell envelope in the ancestor of the Planctomycetales coincided with the emergence of budding and other unique cellular phenotypes. The results have implications for hypotheses about the process whereby complex cellular features evolve in bacteria.", "doi": "10.1093/gbe/evaa159", "pmid": "32761170", "labels": {"Cryo-EM": "Service", "Integrated Microscopy Technologies Ume\u00e5": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "5882020"}, {"db": "pmc", "key": "PMC7533069"}], "notes": [], "created": "2020-12-10T11:22:52.445Z", "modified": "2024-01-16T13:48:41.787Z"}, {"entity": "publication", "iuid": "16f46fa1ca9d460ab515224b1fdf7084", "links": {"self": {"href": "https://publications.scilifelab.se/publication/16f46fa1ca9d460ab515224b1fdf7084.json"}, "display": {"href": "https://publications.scilifelab.se/publication/16f46fa1ca9d460ab515224b1fdf7084"}}, "title": "Xdrop: Targeted sequencing of long DNA molecules from low input samples using droplet sorting.", "authors": [{"family": "Madsen", "given": "Esben B", "initials": "EB", "orcid": "0000-0001-8042-4337", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ba99884e9e84c67b08a6dd0febd0304.json"}}, {"family": "H\u00f6ijer", "given": "Ida", "initials": "I", "orcid": "0000-0002-3915-3384", "researcher": {"href": "https://publications.scilifelab.se/researcher/4ba4ce20b1b447ada4fdc8256211436e.json"}}, {"family": "Kvist", "given": "Thomas", "initials": "T"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Mikkelsen", "given": "Marie J", "initials": "MJ"}], "type": "journal article", "published": "2020-09-00", "journal": {"title": "Hum. Mutat.", "issn": "1098-1004", "volume": "41", "issue": "9", "pages": "1671-1679", "issn-l": "1059-7794"}, "abstract": "Long-read sequencing can resolve regions of the genome that are inaccessible to short reads, and therefore are ideal for genome-gap closure, solving structural rearrangements and sequencing through repetitive elements. Here we introduce the Xdrop technology: a novel microfluidic-based system that allows for targeted enrichment of long DNA molecules starting from only a few nanograms of DNA. Xdrop is based on the isolation of long DNA fragments in millions of droplets, where the droplets containing a target sequence of interest are fluorescently labeled and sorted using flow cytometry. The final product from the Xdrop procedure is an enriched population of long DNA molecules that can be investigated by sequencing. To demonstrate the capability of Xdrop, we performed enrichment of the human papilloma virus 18 integrated into the genome of human HeLa cells. Analysis of the sequencing reads resolved three HPV18-chr8 integrations at base-pair resolution, and the captured fragments extended up to 30 kb into the human genome at the integration sites. Further, we enriched the complete TP53 locus in a leukemia cell line and could successfully phase coexisting mutations using PacBio sequencing. In summary, our results show that Xdrop is an efficient enrichment technology for studying complex genomic regions.", "doi": "10.1002/humu.24063", "pmid": "32516842", "labels": {"National Genomics Infrastructure": "Technology development", "NGI Uppsala (Uppsala Genome Center)": "Technology development", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7496172"}], "notes": [], "created": "2020-06-16T05:00:02.423Z", "modified": "2024-01-16T13:48:41.796Z"}, {"entity": "publication", "iuid": "d1a66cc65c1c4d90bc501a532dbb1cc7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d1a66cc65c1c4d90bc501a532dbb1cc7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d1a66cc65c1c4d90bc501a532dbb1cc7"}}, "title": "The impact of damage-associated molecular patterns on the neurotransmitter release and gene expression in the ex vivo rat carotid body.", "authors": [{"family": "Mkrtchian", "given": "Souren", "initials": "S", "orcid": "0000-0001-9801-2736", "researcher": {"href": "https://publications.scilifelab.se/researcher/e8d9ca2998c8420eaccaec545f606b64.json"}}, {"family": "K\u00e5hlin", "given": "Jessica", "initials": "J"}, {"family": "G\u00f3mez-Gal\u00e1n", "given": "Marta", "initials": "M"}, {"family": "Ebberyd", "given": "Anette", "initials": "A"}, {"family": "Yoshitake", "given": "Takashi", "initials": "T"}, {"family": "Schmidt", "given": "Staffan", "initials": "S"}, {"family": "Kehr", "given": "Jan", "initials": "J"}, {"family": "Hildenborg", "given": "Malin", "initials": "M"}, {"family": "Jonsson Fagerlund", "given": "Malin", "initials": "M"}, {"family": "Erlandsson Harris", "given": "Helena", "initials": "H"}, {"family": "Eriksson", "given": "Lars I", "initials": "LI"}], "type": "journal article", "published": "2020-09-00", "journal": {"title": "Exp. Physiol.", "issn": "1469-445X", "volume": "105", "issue": "9", "pages": "1634-1647", "issn-l": "0958-0670"}, "abstract": "What is the central question of this study? Are carotid bodies (CBs) modulated by the damage-associated molecular patterns (DAMPs) and humoral factors of aseptic tissue injury? What are the main findings and their importance? DAMPs (HMGB1, S100 A8/A9) and blood plasma from rats subjected to tibia surgery, a model of aseptic injury, stimulate the release of neurotransmitters (ATP, dopamine) and TNF-\u03b1 from ex vivo rat CBs. All-thiol HMGB1 mediates upregulation of immune-related biological pathways. These data suggest regulation of CB function by endogenous mediators of innate immunity.\n\nThe glomus cells of carotid bodies (CBs) are the primary sensors of arterial partial O2 and CO2 tensions and moreover serve as multimodal receptors responding also to other stimuli, such as pathogen-associated molecular patterns (PAMPs) produced by acute infection. Modulation of CB function by excessive amounts of these immunomodulators is suggested to be associated with a detrimental hyperinflammatory state. We have hypothesized that yet another class of immunomodulators, endogenous danger-associated molecular patterns (DAMPs), released upon aseptic tissue injury and recognized by the same pathogen recognition receptors as PAMPs, might modulate the CB activity in a fashion similar to PAMPs. We have tested this hypothesis by exposing rat CBs to various DAMPs, such as HMGB1 (all-thiol and disulfide forms) and S100 A8/A9 in a series of ex vivo experiments that demonstrated the release of dopamine and ATP, neurotransmitters known to mediate CB homeostatic responses. We observed a similar response after incubating CBs with conditioned blood plasma obtained from the rats subjected to tibia surgery, a model of aseptic injury. In addition, we have investigated global gene expression in the rat CB using an RNA sequencing approach. Differential gene expression analysis showed all-thiol HMGB1-driven upregulation of a number of prominent pro-inflammatory markers including Il1\u03b1 and Il1\u03b2. Interestingly, conditioned plasma had a more profound effect on the CB transcriptome resulting in inhibition rather than activation of the immune-related pathways. These data are the first to suggest potential modulation of CB function by endogenous mediators of innate immunity.", "doi": "10.1113/EP088705", "pmid": "32652583", "labels": {"NGI Stockholm (Genomics Applications)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service"}, "xrefs": [], "notes": [], "created": "2021-01-08T16:29:48.218Z", "modified": "2021-11-10T12:47:37.875Z"}, {"entity": "publication", "iuid": "ac7ab01a344b4cbb87bc8b19e372caab", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ac7ab01a344b4cbb87bc8b19e372caab.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ac7ab01a344b4cbb87bc8b19e372caab"}}, "title": "Reconstructing marine plankton food web interactions using DNA metabarcoding.", "authors": [{"family": "Zamora-Terol", "given": "Sara", "initials": "S", "orcid": "0000-0002-7822-3197", "researcher": {"href": "https://publications.scilifelab.se/researcher/25e1b401fc9a49c5b6f89eaa18f89a57.json"}}, {"family": "Novotny", "given": "Andreas", "initials": "A"}, {"family": "Winder", "given": "Monika", "initials": "M"}], "type": "journal article", "published": "2020-09-00", "journal": {"title": "Mol. Ecol.", "issn": "1365-294X", "volume": "29", "issue": "17", "pages": "3380-3395", "issn-l": "0962-1083"}, "abstract": "Knowledge of zooplankton in situ diet is critical for accurate assessment of marine ecosystem function and structure, but due to methodological constraints, there is still a limited understanding of ecological networks in marine ecosystems. Here, we used DNA-metabarcoding to study trophic interactions, with the aim to unveil the natural diet of zooplankton species under temporal variation of food resources. Several target consumers, including copepods and cladocerans, were investigated by sequencing 16S rRNA and 18S rRNA genes to identify prokaryote and eukaryote potential prey present in their guts. During the spring phytoplankton bloom, we found a dominance of diatom and dinoflagellate trophic links to copepods. During the summer period, zooplankton including cladocerans showed a more diverse diet dominated by cyanobacteria and heterotrophic prey. Our study suggests that copepods present trophic plasticity, changing their natural diet over seasons, and adapting their feeding strategies to the available prey spectrum, with some species being more selective. We did not find a large overlap of prey consumed by copepods and cladocerans, based on prey diversity found in their guts, suggesting that they occupy different roles in the trophic web. This study represents the first molecular approach to investigate several zooplankton-prey associations under seasonal variation, and highlights how, unlike other techniques, the diversity coverage is high when using DNA, allowing the possibility to detect a wide range of trophic interactions in plankton communities.", "doi": "10.1111/mec.15555", "pmid": "32681684", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [], "notes": [], "created": "2020-12-07T16:34:37.952Z", "modified": "2024-01-16T13:48:41.803Z"}, {"entity": "publication", "iuid": "217d4684484246f2aec3ad0c479d36a0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/217d4684484246f2aec3ad0c479d36a0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/217d4684484246f2aec3ad0c479d36a0"}}, "title": "Linked-read sequencing enables haplotype-resolved resequencing at population scale.", "authors": [{"family": "Lutgen", "given": "Dave", "initials": "D", "orcid": "0000-0003-0793-3930", "researcher": {"href": "https://publications.scilifelab.se/researcher/68173a10b32e4dca953933b92e0cec4e.json"}}, {"family": "Ritter", "given": "Raphael", "initials": "R"}, {"family": "Olsen", "given": "Remi-Andr\u00e9", "initials": "RA"}, {"family": "Schielzeth", "given": "Holger", "initials": "H", "orcid": "0000-0002-9124-2261", "researcher": {"href": "https://publications.scilifelab.se/researcher/56d7e24b36a24560bafa92f08848ac46.json"}}, {"family": "Gruselius", "given": "Joel", "initials": "J"}, {"family": "Ewels", "given": "Philip", "initials": "P", "orcid": "0000-0003-4101-2502", "researcher": {"href": "https://publications.scilifelab.se/researcher/9d0fd82fe18b41539a761c55075f31d6.json"}}, {"family": "Garc\u00eda", "given": "Jes\u00fas T", "initials": "JT", "orcid": "0000-0003-4126-9658", "researcher": {"href": "https://publications.scilifelab.se/researcher/699bf85902454a43aeef0a075ed38a39.json"}}, {"family": "Shirihai", "given": "Hadoram", "initials": "H"}, {"family": "Schweizer", "given": "Manuel", "initials": "M"}, {"family": "Suh", "given": "Alexander", "initials": "A", "orcid": "0000-0002-8979-9992", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e39e1313d894596a6c4ed949e43e019.json"}}, {"family": "Burri", "given": "Reto", "initials": "R", "orcid": "0000-0002-1813-0079", "researcher": {"href": "https://publications.scilifelab.se/researcher/68f21e70e2864b42ab9fc532c14c069c.json"}}], "type": "journal article", "published": "2020-09-00", "journal": {"volume": "20", "issn": "1755-0998", "issue": "5", "pages": "1311-1322", "title": "Mol Ecol Resour", "issn-l": "1755-098X"}, "abstract": "The feasibility to sequence entire genomes of virtually any organism provides unprecedented insights into the evolutionary history of populations and species. Nevertheless, many population genomic inferences - including the quantification and dating of admixture, introgression and demographic events, and inference of selective sweeps - are still limited by the lack of high-quality haplotype information. The newest generation of sequencing technology now promises significant progress. To establish the feasibility of haplotype-resolved genome resequencing at population scale, we investigated properties of linked-read sequencing data of songbirds of the genus Oenanthe across a range of sequencing depths. Our results based on the comparison of downsampled (25\u00d7, 20\u00d7, 15\u00d7, 10\u00d7, 7\u00d7, and 5\u00d7) with high-coverage data (46-68\u00d7) of seven bird genomes mapped to a reference suggest that phasing contiguities and accuracies adequate for most population genomic analyses can be reached already with moderate sequencing effort. At 15\u00d7 coverage, phased haplotypes span about 90% of the genome assembly, with 50% and 90% of phased sequences located in phase blocks longer than 1.25-4.6 Mb (N50) and 0.27-0.72 Mb (N90). Phasing accuracy reaches beyond 99% starting from 15\u00d7 coverage. Higher coverages yielded higher contiguities (up to about 7 Mb/1 Mb [N50/N90] at 25\u00d7 coverage), but only marginally improved phasing accuracy. Phase block contiguity improved with input DNA molecule length; thus, higher-quality DNA may help keeping sequencing costs at bay. In conclusion, even for organisms with gigabase-sized genomes like birds, linked-read sequencing at moderate depth opens an affordable avenue towards haplotype-resolved genome resequencing at population scale.", "doi": "10.1111/1755-0998.13192", "pmid": "32419391", "labels": {"National Genomics Infrastructure": "Collaborative", "NGI Stockholm (Genomics Applications)": "Collaborative", "NGI Stockholm (Genomics Production)": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [], "notes": [], "created": "2020-06-01T16:55:32.608Z", "modified": "2024-01-16T13:48:41.811Z"}, {"entity": "publication", "iuid": "b4d0b1c447554140a71deee30c1f4e81", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b4d0b1c447554140a71deee30c1f4e81.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b4d0b1c447554140a71deee30c1f4e81"}}, "title": "Index hopping on the Illumina HiseqX platform and its consequences for ancient DNA studies.", "authors": [{"family": "van der Valk", "given": "Tom", "initials": "T", "orcid": "0000-0001-6582-3452", "researcher": {"href": "https://publications.scilifelab.se/researcher/f56ca19cfa4f4909be996b2c99ec24f1.json"}}, {"family": "Vezzi", "given": "Francesco", "initials": "F"}, {"family": "Ormestad", "given": "Mattias", "initials": "M"}, {"family": "Dal\u00e9n", "given": "Love", "initials": "L", "orcid": "0000-0001-8270-7613", "researcher": {"href": "https://publications.scilifelab.se/researcher/48ecf726779249ac9d12f4f7a1cc62bf.json"}}, {"family": "Guschanski", "given": "Katerina", "initials": "K", "orcid": "0000-0002-8493-5457", "researcher": {"href": "https://publications.scilifelab.se/researcher/84b8b0757f02429b9bd419acb42ab6a3.json"}}], "type": "journal article", "published": "2020-09-00", "journal": {"volume": "20", "issn": "1755-0998", "issue": "5", "title": "Mol Ecol Resour", "pages": "1171-1181", "issn-l": "1755-098X"}, "abstract": "The high-throughput capacities of the Illumina sequencing platforms and the possibility to label samples individually have encouraged wide use of sample multiplexing. However, this practice results in read misassignment (usually <1%) across samples sequenced on the same lane. Alarmingly high rates of read misassignment of up to 10% were reported for lllumina sequencing machines with exclusion amplification chemistry. This may make use of these platforms prohibitive, particularly in studies that rely on low-quantity and low-quality samples, such as historical and archaeological specimens. Here, we use barcodes, short sequences that are ligated to both ends of the DNA insert, to directly quantify the rate of index hopping in 100-year old museum-preserved gorilla (Gorilla beringei) samples. Correcting for multiple sources of noise, we identify on average 0.470% of reads containing a hopped index. We show that sample-specific quantity of misassigned reads depends on the number of reads that any given sample contributes to the total sequencing pool, so that samples with few sequenced reads receive the greatest proportion of misassigned reads. This particularly affects ancient DNA samples, as these frequently differ in their DNA quantity and endogenous content. Through simulations we show that even low rates of index hopping, as reported here, can lead to biases in ancient DNA studies when multiplexing samples with vastly different quantities of endogenous material.", "doi": "10.1111/1755-0998.13009", "pmid": "30848092", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [], "notes": [], "created": "2019-12-02T17:19:31.114Z", "modified": "2024-01-16T13:48:41.825Z"}, {"entity": "publication", "iuid": "82661edac9d74b09b7e33a0ef24eaae1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/82661edac9d74b09b7e33a0ef24eaae1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/82661edac9d74b09b7e33a0ef24eaae1"}}, "title": "Hyperandrogenism and insulin resistance modulate gravid uterine and placental ferroptosis in PCOS-like rats.", "authors": [{"family": "Zhang", "given": "Yuehui", "initials": "Y"}, {"family": "Hu", "given": "Min", "initials": "M"}, {"family": "Jia", "given": "Wenyan", "initials": "W"}, {"family": "Liu", "given": "Guoqi", "initials": "G"}, {"family": "Zhang", "given": "Jiao", "initials": "J"}, {"family": "Wang", "given": "Bing", "initials": "B"}, {"family": "Li", "given": "Juan", "initials": "J"}, {"family": "Cui", "given": "Peng", "initials": "P"}, {"family": "Li", "given": "Xin", "initials": "X"}, {"family": "Lager", "given": "Susanne", "initials": "S"}, {"family": "Sferruzzi-Perri", "given": "Amanda Nancy", "initials": "AN"}, {"family": "Han", "given": "Yanhua", "initials": "Y"}, {"family": "Liu", "given": "Songjiang", "initials": "S"}, {"family": "Wu", "given": "Xiaoke", "initials": "X"}, {"family": "Br\u00e4nnstr\u00f6m", "given": "Mats", "initials": "M"}, {"family": "Shao", "given": "Linus R", "initials": "LR"}, {"family": "Billig", "given": "H\u00e5kan", "initials": "H"}], "type": "journal article", "published": "2020-09-00", "journal": {"title": "J Endocrinol", "issn": "1479-6805", "volume": "246", "issue": "3", "pages": "247-263", "issn-l": null}, "abstract": "Women with polycystic ovary syndrome (PCOS) have hyperandrogenism and insulin resistance and a high risk of miscarriage during pregnancy. Similarly, in rats, maternal exposure to 5\u03b1-dihydrotestosterone (DHT) and insulin from gestational day 7.5 to 13.5 leads to hyperandrogenism and insulin resistance and subsequently increased fetal loss. A variety of hormonal and metabolic stimuli are able to trigger different types of regulated cell death under physiological and pathological conditions. These include ferroptosis, apoptosis and necroptosis. We hypothesized that, in rats, maternal hyperandrogenism and insulin-resistance-induced fetal loss is mediated, at least in part, by changes in the ferroptosis, apoptosis and necroptosis pathways in the gravid uterus and placenta. Compared with controls, we found that co-exposure to DHT and insulin led to decreased levels of glutathione peroxidase 4 (GPX4) and glutathione, increased glutathione + glutathione disulfide and malondialdehyde, aberrant expression of ferroptosis-associated genes (Acsl4, Tfrc, Slc7a11, and Gclc), increased iron deposition and activated ERK/p38/JNK phosphorylation in the gravid uterus. In addition, we observed shrunken mitochondria with electron-dense cristae, which are key features of ferroptosis-related mitochondrial morphology, as well as increased expression of Dpp4, a mitochondria-encoded gene responsible for ferroptosis induction in the uteri of rats co-exposed to DHT and insulin. However, in the placenta, DHT and insulin exposure only partially altered the expression of ferroptosis-related markers (e.g. region-dependent GPX4, glutathione + glutathione disulfide, malondialdehyde, Gls2 and Slc7a11 mRNAs, and phosphorylated p38 levels). Moreover, we found decreased expression of Dpp4 mRNA and increased expression of Cisd1 mRNA in placentas of rats co-exposed to DHT and insulin. Further, DHT + insulin-exposed pregnant rats exhibited decreased apoptosis in the uterus and increased necroptosis in the placenta. Our findings suggest that maternal hyperandrogenism and insulin resistance causes the activation of ferroptosis in the gravid uterus and placenta, although this is mediated via different mechanisms operating at the molecular and cellular levels. Our data also suggest that apoptosis and necroptosis may play a role in coordinating or compensating for hyperandrogenism and insulin-resistance-induced ferroptosis when the gravid uterus and placenta are dysfunctional.", "doi": "10.1530/JOE-20-0155", "pmid": "32590339", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "JOE-20-0155"}], "notes": [], "created": "2023-02-16T08:10:35.403Z", "modified": "2023-02-16T08:13:23.023Z"}, {"entity": "publication", "iuid": "5fd797c1379649c595a3fe25052f4e25", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5fd797c1379649c595a3fe25052f4e25.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5fd797c1379649c595a3fe25052f4e25"}}, "title": "Hemolytic uremic syndrome caused by Shiga toxin-producing Escherichia coli in children: incidence, risk factors, and clinical outcome.", "authors": [{"family": "Ylinen", "given": "Elisa", "initials": "E", "orcid": "0000-0002-3540-7033", "researcher": {"href": "https://publications.scilifelab.se/researcher/3b40a9932eec404d811a54aef1a5ca26.json"}}, {"family": "Salmenlinna", "given": "Saara", "initials": "S"}, {"family": "Halkilahti", "given": "Jani", "initials": "J"}, {"family": "Jahnukainen", "given": "Timo", "initials": "T"}, {"family": "Korhonen", "given": "Linda", "initials": "L"}, {"family": "Virkkala", "given": "Tiia", "initials": "T"}, {"family": "Rimhanen-Finne", "given": "Ruska", "initials": "R"}, {"family": "Nuutinen", "given": "Matti", "initials": "M"}, {"family": "Kataja", "given": "Janne", "initials": "J"}, {"family": "Arikoski", "given": "Pekka", "initials": "P"}, {"family": "Linkosalo", "given": "Laura", "initials": "L"}, {"family": "Bai", "given": "Xiangning", "initials": "X"}, {"family": "Matussek", "given": "Andreas", "initials": "A"}, {"family": "Jalanko", "given": "Hannu", "initials": "H"}, {"family": "Sax\u00e9n", "given": "Harri", "initials": "H"}], "type": "journal article", "published": "2020-09-00", "journal": {"title": "Pediatr Nephrol", "issn": "1432-198X", "issn-l": null, "volume": "35", "issue": "9", "pages": "1749-1759"}, "abstract": "Hemolytic uremic syndrome (HUS) is a multisystemic disease. In a nationwide study, we characterized the incidence, clinical course, and prognosis of HUS caused by Shiga toxin (Stx)-producing Escherichia coli (STEC) strains with emphasis on risk factors, disease severity, and long-term outcome.\n\nThe data on pediatric HUS patients from 2000 to 2016 were collected from the medical records. STEC isolates from fecal cultures of HUS and non-HUS patients were collected from the same time period and characterized by whole genome sequencing analysis.\n\nFifty-eight out of 262 culture-positive cases developed verified (n = 58, 22%) STEC-HUS. Another 29 cases had probable STEC-HUS, the annual incidence of STEC-HUS being 0.5 per 100,000 children. Eleven different serogroups were detected, O157 being the most common (n = 37, 66%). Age under 3 years (OR 2.4), stx2 (OR 9.7), and stx2a (OR 16.6) were found to be risk factors for HUS. Fifty-five patients (63%) needed dialysis. Twenty-nine patients (33%) developed major neurological symptoms. Complete renal recovery was observed in 57 patients after a median 4.0 years of follow-up. Age under 3 years, leukocyte count over 20 \u00d7 109/L, and need for dialysis were predictive factors for poor renal outcome.\n\nAge under 3 years, stx2, and stx2a were risk factors for HUS in STEC-positive children. However, serogroup or stx types did not predict the renal outcome or major CNS symptoms.", "doi": "10.1007/s00467-020-04560-0", "pmid": "32323005", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1007/s00467-020-04560-0"}, {"db": "pmc", "key": "PMC7385025"}], "notes": [], "created": "2021-01-03T10:17:09.942Z", "modified": "2021-11-10T12:47:42.297Z"}, {"entity": "publication", "iuid": "adf88ccfb5234e1a956955924cb042b7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/adf88ccfb5234e1a956955924cb042b7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/adf88ccfb5234e1a956955924cb042b7"}}, "title": "Genetic comorbidity between major depression and cardio-metabolic traits, stratified by age at onset of major depression.", "authors": [{"family": "Hagenaars", "given": "Saskia P", "initials": "SP", "orcid": "0000-0001-9697-8596", "researcher": {"href": "https://publications.scilifelab.se/researcher/2648f5c01c0d497c96f18f3836117aac.json"}}, {"family": "Coleman", "given": "Jonathan R I", "initials": "JRI", "orcid": "0000-0002-6759-0944", "researcher": {"href": "https://publications.scilifelab.se/researcher/91f9f96c887447918926b36de9cfc820.json"}}, {"family": "Choi", "given": "Shing Wan", "initials": "SW"}, {"family": "Gaspar", "given": "H\u00e9l\u00e9na", "initials": "H"}, {"family": "Adams", "given": "Mark J", "initials": "MJ"}, {"family": "Howard", "given": "David M", "initials": "DM"}, {"family": "Hodgson", "given": "Karen", "initials": "K"}, {"family": "Traylor", "given": "Matthew", "initials": "M"}, {"family": "Air", "given": "Tracy M", "initials": "TM"}, {"family": "Andlauer", "given": "Till F M", "initials": "TFM", "orcid": "0000-0002-2917-5889", "researcher": {"href": "https://publications.scilifelab.se/researcher/66b66e6c499e459ba61db4cbae3e22a9.json"}}, {"family": "Arolt", "given": "Volker", "initials": "V"}, {"family": "Baune", "given": "Bernhard T", "initials": "BT"}, {"family": "Binder", "given": "Elisabeth B", "initials": "EB"}, {"family": "Blackwood", "given": "Douglas H R", "initials": "DHR"}, {"family": "Boomsma", "given": "Dorret I", "initials": "DI"}, {"family": "Campbell", "given": "Archie", "initials": "A"}, {"family": "Cearns", "given": "Micah", "initials": "M"}, {"family": "Czamara", "given": "Darina", "initials": "D", "orcid": "0000-0001-7381-904X", "researcher": {"href": "https://publications.scilifelab.se/researcher/0e9a8a7d605d4f63a311fc8a211422a6.json"}}, {"family": "Dannlowski", "given": "Udo", "initials": "U"}, {"family": "Domschke", "given": "Katharina", "initials": "K"}, {"family": "de Geus", "given": "Eco J C", "initials": "EJC"}, {"family": "Hamilton", "given": "Steven P", "initials": "SP"}, {"family": "Hayward", "given": "Caroline", "initials": "C"}, {"family": "Hickie", "given": "Ian B", "initials": "IB"}, {"family": "Hottenga", "given": "Jouke Jan", "initials": "JJ"}, {"family": "Ising", "given": "Marcus", "initials": "M"}, {"family": "Jones", "given": "Ian", "initials": "I"}, {"family": "Jones", "given": "Lisa", "initials": "L"}, {"family": "Kutalik", "given": "Zoltan", "initials": "Z"}, {"family": "Lucae", "given": "Susanne", "initials": "S"}, {"family": "Martin", "given": "Nicholas G", "initials": "NG", "orcid": "0000-0003-4069-8020", "researcher": {"href": "https://publications.scilifelab.se/researcher/1b445e5935f74fd6a71b2e92a9dac176.json"}}, {"family": "Milaneschi", "given": "Yuri", "initials": "Y"}, {"family": "Mueller-Myhsok", "given": "Bertram", "initials": "B"}, {"family": "Owen", "given": "Michael J", "initials": "MJ"}, {"family": "Padmanabhan", "given": "Sandosh", "initials": "S"}, {"family": "Penninx", "given": "Brenda W J H", "initials": "BWJH"}, {"family": "Pistis", "given": "Giorgio", "initials": "G"}, {"family": "Porteous", "given": "David J", "initials": "DJ"}, {"family": "Preisig", "given": "Martin", "initials": "M"}, {"family": "Ripke", "given": "Stephan", "initials": "S"}, {"family": "Shyn", "given": "Stanley I", "initials": "SI"}, {"family": "Sullivan", "given": "Patrick F", "initials": "PF"}, {"family": "Whitfield", "given": "John B", "initials": "JB"}, {"family": "Wray", "given": "Naomi R", "initials": "NR", "orcid": "0000-0001-7421-3357", "researcher": {"href": "https://publications.scilifelab.se/researcher/15a175036d9f44f9b4090d7d431f78d7.json"}}, {"family": "McIntosh", "given": "Andrew M", "initials": "AM"}, {"family": "Deary", "given": "Ian J", "initials": "IJ"}, {"family": "Breen", "given": "Gerome", "initials": "G"}, {"family": "Lewis", "given": "Cathryn M", "initials": "CM"}], "type": "journal article", "published": "2020-09-00", "journal": {"title": "Am. J. Med. Genet. B Neuropsychiatr. Genet.", "issn": "1552-485X", "volume": "183", "issue": "6", "pages": "309-330", "issn-l": "1552-4841"}, "abstract": "It is imperative to understand the specific and shared etiologies of major depression and cardio-metabolic disease, as both traits are frequently comorbid and each represents a major burden to society. This study examined whether there is a genetic association between major depression and cardio-metabolic traits and if this association is stratified by age at onset for major depression. Polygenic risk scores analysis and linkage disequilibrium score regression was performed to examine whether differences in shared genetic etiology exist between depression case control status (N cases = 40,940, N controls = 67,532), earlier (N = 15,844), and later onset depression (N = 15,800) with body mass index, coronary artery disease, stroke, and type 2 diabetes in 11 data sets from the Psychiatric Genomics Consortium, Generation Scotland, and UK Biobank. All cardio-metabolic polygenic risk scores were associated with depression status. Significant genetic correlations were found between depression and body mass index, coronary artery disease, and type 2 diabetes. Higher polygenic risk for body mass index, coronary artery disease, and type 2 diabetes was associated with both early and later onset depression, while higher polygenic risk for stroke was associated with later onset depression only. Significant genetic correlations were found between body mass index and later onset depression, and between coronary artery disease and both early and late onset depression. The phenotypic associations between major depression and cardio-metabolic traits may partly reflect their overlapping genetic etiology irrespective of the age depression first presents.", "doi": "10.1002/ajmg.b.32807", "pmid": "32681593", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7991693"}, {"db": "mid", "key": "NIHMS1669188"}], "notes": [], "created": "2020-08-04T14:50:09.256Z", "modified": "2021-11-10T12:49:11.517Z"}, {"entity": "publication", "iuid": "28b02c11dee94c2dac39ef643d0f95e9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/28b02c11dee94c2dac39ef643d0f95e9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/28b02c11dee94c2dac39ef643d0f95e9"}}, "title": "Genetic association of gemcitabine/carboplatin-induced leukopenia and neutropenia in non-small cell lung cancer patients using whole-exome sequencing.", "authors": [{"family": "Svedberg", "given": "Anna", "initials": "A"}, {"family": "Bj\u00f6rn", "given": "Niclas", "initials": "N"}, {"family": "Sigurgeirsson", "given": "Benjam\u00edn", "initials": "B"}, {"family": "Pradhananga", "given": "Sailendra", "initials": "S"}, {"family": "Brand\u00e9n", "given": "Eva", "initials": "E"}, {"family": "Koyi", "given": "Hirsh", "initials": "H"}, {"family": "Lewensohn", "given": "Rolf", "initials": "R"}, {"family": "De Petris", "given": "Luigi", "initials": "L"}, {"family": "Apell\u00e1niz-Ruiz", "given": "Mar\u00eda", "initials": "M"}, {"family": "Rodr\u00edguez-Antona", "given": "Cristina", "initials": "C"}, {"family": "Lundeberg", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4313-1601", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a4e6ca0f29b4ead8569e2729481c3e0.json"}}, {"family": "Gr\u00e9en", "given": "Henrik", "initials": "H"}], "type": "journal article", "published": "2020-09-00", "journal": {"title": "Lung Cancer", "issn": "1872-8332", "volume": "147", "issue": null, "pages": "106-114", "issn-l": "0169-5002"}, "abstract": "Gemcitabine/carboplatin treatment is known to cause severe adverse drug reactions which can lead to the need for reduction or cessation of chemotherapy. It would be beneficial to identify patients at risk of severe hematological toxicity in advance before treatment start. This study aims to identify genetic markers for gemcitabine/carboplatin-induced leukopenia and neutropenia in non-small cell lung cancer patients.\n\nWhole-exome sequencing was performed on 215 patients. Association analysis was performed on single-nucleotide variants (SNVs) and genes, and the validation was based on an independent genome-wide association study (GWAS). Based on the association and validation analyses the genetic variants were then selected for and used in weighted genetic risk score (wGRS) prediction models for leukopenia and neutropenia.\n\nAssociation analysis identified 50 and 111 SNVs, and 12 and 20 genes, for leukopenia and neutropenia, respectively. Of these SNVS 20 and 19 were partially validated for leukopenia and neutropenia, respectively. The genes SVIL (p = 2.48E-06) and EFCAB2 (p = 4.63E-06) were significantly associated with leukopenia contain the partially validated SNVs rs3740003, rs10160013, rs1547169, rs10927386 and rs10927387. The wGRS prediction models showed significantly different risk scores for high and low toxicity patients.\n\nWe have identified and partially validated genetic biomarkers in SNVs and genes correlated to gemcitabine/carboplatin-induced leukopenia and neutropenia and created wGRS models for predicting the risk of chemotherapy-induced hematological toxicity. These results provide a strong foundation for further studies of chemotherapy-induced toxicity.", "doi": "10.1016/j.lungcan.2020.07.005", "pmid": "32683206", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service"}, "xrefs": [{"db": "pii", "key": "S0169-5002(20)30516-X"}], "notes": [], "created": "2020-12-07T16:27:05.896Z", "modified": "2021-11-10T12:47:43.408Z"}, {"entity": "publication", "iuid": "f8cca6c2565442529e2d305f9df9d713", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f8cca6c2565442529e2d305f9df9d713.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f8cca6c2565442529e2d305f9df9d713"}}, "title": "Defining the proteolytic landscape during enterovirus infection.", "authors": [{"family": "Saeed", "given": "Mohsan", "initials": "M", "orcid": "0000-0001-8505-7054", "researcher": {"href": "https://publications.scilifelab.se/researcher/b2b550e450e648b88973f7806e69d9e0.json"}}, {"family": "Kapell", "given": "Sebastian", "initials": "S", "orcid": "0000-0001-9304-558X", "researcher": {"href": "https://publications.scilifelab.se/researcher/cffd944f88e54ed6a910183ba49ef656.json"}}, {"family": "Hertz", "given": "Nicholas T", "initials": "NT", "orcid": "0000-0002-6527-6898", "researcher": {"href": "https://publications.scilifelab.se/researcher/3718edc733f9468b8bc3986691d78d11.json"}}, {"family": "Wu", "given": "Xianfang", "initials": "X"}, {"family": "Bell", "given": "Kierstin", "initials": "K"}, {"family": "Ashbrook", "given": "Alison W", "initials": "AW", "orcid": "0000-0003-1114-1426", "researcher": {"href": "https://publications.scilifelab.se/researcher/4c44306c97f44ea9af73e91263c7fca0.json"}}, {"family": "Mark", "given": "Milica Tesic", "initials": "MT"}, {"family": "Zebroski", "given": "Henry A", "initials": "HA", "orcid": "0000-0003-3012-2335", "researcher": {"href": "https://publications.scilifelab.se/researcher/5d1648b613134dcb940eed28dd8ada81.json"}}, {"family": "Neal", "given": "Maxwell L", "initials": "ML", "orcid": "0000-0002-2390-6572", "researcher": {"href": "https://publications.scilifelab.se/researcher/c26ff0117fa24bc1b0eb24c0eeb99065.json"}}, {"family": "Flodstr\u00f6m-Tullberg", "given": "Malin", "initials": "M", "orcid": "0000-0003-2685-2052", "researcher": {"href": "https://publications.scilifelab.se/researcher/bb6d04afbe8141c2b9297854de64dab8.json"}}, {"family": "MacDonald", "given": "Margaret R", "initials": "MR", "orcid": "0000-0001-5177-2068", "researcher": {"href": "https://publications.scilifelab.se/researcher/dfa709cba63140a381f532f9d5379d7a.json"}}, {"family": "Aitchison", "given": "John D", "initials": "JD"}, {"family": "Molina", "given": "Henrik", "initials": "H"}, {"family": "Rice", "given": "Charles M", "initials": "CM", "orcid": "0000-0003-3087-8079", "researcher": {"href": "https://publications.scilifelab.se/researcher/34f03294e8e748779a10ecfcb1bf66b2.json"}}], "type": "journal article", "published": "2020-09-00", "journal": {"title": "PLoS Pathog.", "issn": "1553-7374", "volume": "16", "issue": "9", "pages": "e1008927", "issn-l": "1553-7366"}, "abstract": "Viruses cleave cellular proteins to remodel the host proteome. The study of these cleavages has revealed mechanisms of immune evasion, resource exploitation, and pathogenesis. However, the full extent of virus-induced proteolysis in infected cells is unknown, mainly because until recently the technology for a global view of proteolysis within cells was lacking. Here, we report the first comprehensive catalog of proteins cleaved upon enterovirus infection and identify the sites within proteins where the cleavages occur. We employed multiple strategies to confirm protein cleavages and assigned them to one of the two enteroviral proteases. Detailed characterization of one substrate, LSM14A, a p body protein with a role in antiviral immunity, showed that cleavage of this protein disrupts its antiviral function. This study yields a new depth of information about the host interface with a group of viruses that are both important biological tools and significant agents of disease.", "doi": "10.1371/journal.ppat.1008927", "pmid": "32997711", "labels": {"Protein Science Facility (PSF)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7549765"}, {"db": "pii", "key": "PPATHOGENS-D-20-01061"}], "notes": [], "created": "2024-04-03T14:18:40.135Z", "modified": "2024-04-03T14:18:41.736Z"}, {"entity": "publication", "iuid": "8005879a074c4abf932ec97a4b9e74b4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8005879a074c4abf932ec97a4b9e74b4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8005879a074c4abf932ec97a4b9e74b4"}}, "title": "DNA methylation variation in the brain of laying hens in relation to differential behavioral patterns.", "authors": [{"family": "Guerrero-Bosagna", "given": "Carlos", "initials": "C"}, {"family": "P\u00e9rtille", "given": "F\u00e1bio", "initials": "F"}, {"family": "Gomez", "given": "Yamenah", "initials": "Y"}, {"family": "Rezaei", "given": "Shiva", "initials": "S"}, {"family": "Gebhardt-Henrich", "given": "Sabine G", "initials": "SG"}, {"family": "V\u00f6geli", "given": "Sabine", "initials": "S"}, {"family": "Stratmann", "given": "Ariane", "initials": "A"}, {"family": "Voelkl", "given": "Bernhard", "initials": "B"}, {"family": "Toscano", "given": "Michael J", "initials": "MJ"}], "type": "journal article", "published": "2020-09-00", "journal": {"title": "Comp Biochem Physiol Part D Genomics Proteomics", "issn": "1878-0407", "volume": "35", "issue": null, "pages": "100700", "issn-l": null}, "abstract": "Domesticated animals are unique to investigate the contribution of genetic and non-genetic factors to specific phenotypes. Among non-genetic factors involved in phenotype formation are epigenetic mechanisms. Here we aimed to identify whether relative DNA methylation differences in the nidopallium between groups of individuals are among the non-genetic factors involved in the emergence of differential behavioral patterns in hens. The nidopallium was selected due to its important role in complex cognitive function (i.e., decision making) in birds. Behavioral patterns that spontaneously emerge in hens living in a highly controlled environment were identified with a unique tracking system that recorded their transitions between pen zones. Behavioral activity patterns were characterized through three classification schemes: (i) daily specific features of behavioral routines (Entropy), (ii) daily spatio-temporal activity patterns (Dynamic Time Warping), and (iii) social leading behavior (Leading Index). Unique differentially methylated regions (DMRs) were identified between behavioral patterns emerging within classification schemes, with entropy having the higher number. Functionally, DTW had double the proportion of affected promoters and half of the distal intergenic regions. Pathway enrichment analysis of DMR-associated genes revealed that Entropy relates mainly to cell cycle checkpoints, Leading Index to mitochondrial function, and DTW to gene expression regulation. Our study suggests that different biological functions within neurons (particularly in the nidopallium) could be responsible for the emergence of distinct behavior patterns and that epigenetic variation within brain tissues would be an important factor to explain behavioral variation.", "doi": "10.1016/j.cbd.2020.100700", "pmid": "32702621", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service"}, "xrefs": [{"db": "pii", "key": "S1744-117X(20)30047-2"}], "notes": [], "created": "2020-12-07T16:34:39.070Z", "modified": "2021-11-10T12:47:44.502Z"}, {"entity": "publication", "iuid": "befd645e5e764eac97f5d53eb795294d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/befd645e5e764eac97f5d53eb795294d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/befd645e5e764eac97f5d53eb795294d"}}, "title": "Comparative analysis of genome-wide DNA methylation in Neurospora.", "authors": [{"family": "Hosseini", "given": "Sara", "initials": "S"}, {"family": "Meunier", "given": "C\u00e9cile", "initials": "C"}, {"family": "Nguyen", "given": "Diem", "initials": "D"}, {"family": "Reimeg\u00e5rd", "given": "Johan", "initials": "J"}, {"family": "Johannesson", "given": "Hanna", "initials": "H", "orcid": "0000-0001-6359-9856", "researcher": {"href": "https://publications.scilifelab.se/researcher/36e8fe278e01470e8cddaaccc5dad596.json"}}], "type": "journal article", "published": "2020-09-00", "journal": {"title": "Epigenetics", "issn": "1559-2308", "volume": "15", "issue": "9", "pages": "972-987", "issn-l": "1559-2294"}, "abstract": "DNA methylation is an epigenetic mark that plays an important role in genetic regulation in eukaryotes. Major progress has been made in dissecting the molecular pathways that regulate DNA methylation. Yet, little is known about DNA methylation variation over evolutionary time. Here we present an investigation of the variation of DNA methylation and transposable element (TE) content in species of the filamentous ascomycetes Neurospora. We generated genome-wide DNA methylation data at single-base resolution, together with genomic TE content and gene expression data, of 10 individuals representing five closely related Neurospora species. We found that the methylation levels were low (ranging from 1.3% to 2.5%) and varied among the genomes in a species-specific way. Furthermore, we found that the TEs over 400 bp long were targeted by DNA methylation, and in all genomes, high methylation correlated with low GC, confirming a conserved link between DNA methylation and Repeat Induced Point (RIP) mutations in this group of fungi. Both TE content and DNA methylation pattern showed phylogenetic signal, and the species with the highest TE load (N. crassa) also exhibited the highest methylation level per TE. Our results suggest that DNA methylation is an evolvable trait and indicate that the genomes of Neurospora are shaped by an evolutionary arms race between TEs and host defence.", "doi": "10.1080/15592294.2020.1741758", "pmid": "32228351", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "NGI Uppsala (Uppsala Genome Center)": "Service", "National Genomics Infrastructure": "Service", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC7518705"}], "notes": [], "created": "2020-04-23T08:47:49.215Z", "modified": "2024-01-16T13:48:41.837Z"}, {"entity": "publication", "iuid": "6fd422b0c1ca473b9416000453b1735b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6fd422b0c1ca473b9416000453b1735b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6fd422b0c1ca473b9416000453b1735b"}}, "title": "A dynamic mutational landscape associated with an inter-regionally diverse immune response in malignant rhabdoid tumour.", "authors": [{"family": "Yasui", "given": "Hiroaki", "initials": "H", "orcid": "0000-0002-2607-5233", "researcher": {"href": "https://publications.scilifelab.se/researcher/4c02c6fd2bea494d9f58b1e10f6b8f2f.json"}}, {"family": "Valind", "given": "Anders", "initials": "A"}, {"family": "Karlsson", "given": "Jenny", "initials": "J"}, {"family": "Pietras", "given": "Christina", "initials": "C"}, {"family": "Jansson", "given": "Caroline", "initials": "C"}, {"family": "Wille", "given": "Joakim", "initials": "J"}, {"family": "Romerius", "given": "Patrik", "initials": "P"}, {"family": "Backman", "given": "Torbj\u00f6rn", "initials": "T"}, {"family": "Gisselsson", "given": "David", "initials": "D"}], "type": "journal article", "published": "2020-09-00", "journal": {"title": "J. Pathol.", "issn": "1096-9896", "volume": "252", "issue": "1", "pages": "22-28", "issn-l": "0022-3417"}, "abstract": "Malignant rhabdoid tumour (MRT) is a childhood neoplasm of high malignancy characterised by biallelic mutation and/or loss of the epigenetic master regulator SMARCB1, accompanied by no or few other oncogenic drivers. In spite of their generally low mutational burden, an intratumoural T-cell response has been reported in a subset of MRTs, indicating that immune checkpoint inhibition may be considered a viable therapy option for some patients. We assess here the evolution over time and space of predicted neoantigens and indicators of immune checkpoint status in two MRT patients who progressed under treatment. Both patients showed an accumulation of novel clonal and subclonal mutations, including predicted neoantigens, in metastases compared to their inferred ancestral clones in the primary tumours. The first patient had peritoneal metastases from an MRT of the liver. Clonal deconvolution revealed polyclonal seeding from the primary tumour to a single metastatic site, followed by a local subclonal burst of mutations. The second patient had a renal MRT with multiple pulmonary metastases, each of which could be traced back to a single genetically unique founder cell, with formation of novel subclones in two metastases. Both patients showed a regionally heterogeneous landscape of predicted neoantigens and of tumour-infiltrating lymphocytes expressing CD8 and PD1. In both patients, some tumour regions fulfilled established criteria for PD-L1 positivity (> 1% of tumour cells), while others did not. This suggests that even in a tumour type like MRT, with a single driver mutation, there can be heterogeneity in neoantigen repertoire, immune response, and biomarkers for checkpoint blockade among sampled locations. This must be taken into account when assessing progressed MRT patients for checkpoint inhibition therapy. \u00a9 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.", "doi": "10.1002/path.5490", "pmid": "32542645", "labels": {"Clinical Genomics Lund": null, "Clinical Genomics": null}, "xrefs": [], "notes": [], "created": "2020-12-01T18:25:53.806Z", "modified": "2021-11-10T12:47:49.926Z"}, {"entity": "publication", "iuid": "2a387a31c3c54f2f9d3abce4e7efdfe2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2a387a31c3c54f2f9d3abce4e7efdfe2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2a387a31c3c54f2f9d3abce4e7efdfe2"}}, "title": "A Shh/Gli-driven three-node timer motif controls temporal identity and fate of neural stem cells.", "authors": [{"family": "Dias", "given": "Jos\u00e9 M", "initials": "JM", "orcid": "0000-0002-1402-0323", "researcher": {"href": "https://publications.scilifelab.se/researcher/82499805c5c24c46b8c2ec6427345c89.json"}}, {"family": "Alekseenko", "given": "Zhanna", "initials": "Z", "orcid": "0000-0002-6560-9699", "researcher": {"href": "https://publications.scilifelab.se/researcher/d78aae6139714fa3ae8221f3fb380b5a.json"}}, {"family": "Jeggari", "given": "Ashwini", "initials": "A", "orcid": "0000-0002-7155-9050", "researcher": {"href": "https://publications.scilifelab.se/researcher/083131be9eab46df9c789fb018316dff.json"}}, {"family": "Boareto", "given": "Marcelo", "initials": "M", "orcid": "0000-0002-9915-6376", "researcher": {"href": "https://publications.scilifelab.se/researcher/992734ee2f564e51b65c3d24770cc337.json"}}, {"family": "Vollmer", "given": "Jannik", "initials": "J", "orcid": "0000-0001-8341-7730", "researcher": {"href": "https://publications.scilifelab.se/researcher/793924a7af814c28a4ad66ff2fabf136.json"}}, {"family": "Kozhevnikova", "given": "Mariya", "initials": "M", "orcid": "0000-0001-9177-6303", "researcher": {"href": "https://publications.scilifelab.se/researcher/a7a4bfdfbcc54403b818b31b24934151.json"}}, {"family": "Wang", "given": "Hui", "initials": "H", "orcid": "0000-0002-5444-1579", "researcher": {"href": "https://publications.scilifelab.se/researcher/38fc15d279b34209a72be7bd71a9338c.json"}}, {"family": "Matise", "given": "Michael P", "initials": "MP", "orcid": "0000-0003-2998-9927", "researcher": {"href": "https://publications.scilifelab.se/researcher/f861ea74deb9478fa475c5036333dfd9.json"}}, {"family": "Alexeyenko", "given": "Andrey", "initials": "A", "orcid": "0000-0001-8812-6481", "researcher": {"href": "https://publications.scilifelab.se/researcher/54b6c0ff12c148dd803f7f72c8af0d14.json"}}, {"family": "Iber", "given": "Dagmar", "initials": "D", "orcid": "0000-0001-8051-1035", "researcher": {"href": "https://publications.scilifelab.se/researcher/26137676787f477fb374d629819d898b.json"}}, {"family": "Ericson", "given": "Johan", "initials": "J", "orcid": "0000-0002-8019-7127", "researcher": {"href": "https://publications.scilifelab.se/researcher/5a093b1609b74f74a8a8546f02946782.json"}}], "type": "journal article", "published": "2020-09-00", "journal": {"title": "Sci Adv", "issn": "2375-2548", "issn-l": "2375-2548", "volume": "6", "issue": "38", "pages": null}, "abstract": "How time is measured by neural stem cells during temporal neurogenesis has remained unresolved. By combining experiments and computational modeling, we define a Shh/Gli-driven three-node timer underlying the sequential generation of motor neurons (MNs) and serotonergic neurons in the brainstem. The timer is founded on temporal decline of Gli-activator and Gli-repressor activities established through down-regulation of Gli transcription. The circuitry conforms an incoherent feed-forward loop, whereby Gli proteins not only promote expression of Phox2b and thereby MN-fate but also account for a delayed activation of a self-promoting transforming growth factor-\u03b2 (Tgf\u03b2) node triggering a fate switch by repressing Phox2b. Hysteresis and spatial averaging by diffusion of Tgf\u03b2 counteract noise and increase temporal accuracy at the population level, providing a functional rationale for the intrinsically programmed activation of extrinsic switch signals in temporal patterning. Our study defines how time is reliably encoded during the sequential specification of neurons.", "doi": "10.1126/sciadv.aba8196", "pmid": "32938678", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "6/38/eaba8196"}, {"db": "pmc", "key": "PMC7494341"}], "notes": [], "created": "2020-12-07T16:28:52.509Z", "modified": "2024-01-16T13:48:41.848Z"}, {"entity": "publication", "iuid": "bd1a87d416a44b78b1e5b21dd61f2b66", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bd1a87d416a44b78b1e5b21dd61f2b66.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bd1a87d416a44b78b1e5b21dd61f2b66"}}, "title": "Sex differences in oncogenic mutational processes.", "authors": [{"family": "Li", "given": "Constance H", "initials": "CH", "orcid": "0000-0002-5487-7225", "researcher": {"href": "https://publications.scilifelab.se/researcher/c1b145ea074a457288ef97554becf7df.json"}}, {"family": "Prokopec", "given": "Stephenie D", "initials": "SD", "orcid": "0000-0001-7936-8577", "researcher": {"href": "https://publications.scilifelab.se/researcher/be46453f056f42fe8a35c0a72201d7e4.json"}}, {"family": "Sun", "given": "Ren X", "initials": "RX"}, {"family": "Yousif", "given": "Fouad", "initials": "F"}, {"family": "Schmitz", "given": "Nathaniel", "initials": "N"}, {"family": "PCAWG Tumour Subtypes and Clinical Translation", "given": "", "initials": ""}, {"family": "Boutros", "given": "Paul C", "initials": "PC", "orcid": "0000-0003-0553-7520", "researcher": {"href": "https://publications.scilifelab.se/researcher/9f627e3789d04a28aa270a5873c5f20b.json"}}, {"family": "PCAWG Consortium", "given": "", "initials": ""}], "type": "journal article", "published": "2020-08-28", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "11", "issue": "1", "pages": "4330", "issn-l": "2041-1723"}, "abstract": "Sex differences have been observed in multiple facets of cancer epidemiology, treatment and biology, and in most cancers outside the sex organs. Efforts to link these clinical differences to specific molecular features have focused on somatic mutations within the coding regions of the genome. Here we report a pan-cancer analysis of sex differences in whole genomes of 1983 tumours of 28 subtypes as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium. We both confirm the results of exome studies, and also uncover previously undescribed sex differences. These include sex-biases in coding and non-coding cancer drivers, mutation prevalence and strikingly, in mutational signatures related to underlying mutational processes. These results underline the pervasiveness of molecular sex differences and strengthen the call for increased consideration of sex in molecular cancer research.", "doi": "10.1038/s41467-020-17359-2", "pmid": "32859912", "labels": {"Clinical Genomics Uppsala": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-17359-2"}, {"db": "pmc", "key": "PMC7455744"}], "notes": [], "created": "2020-12-10T14:46:49.399Z", "modified": "2021-11-10T12:47:52.388Z"}, {"entity": "publication", "iuid": "025e768a51504535a00b3757d24df6d1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/025e768a51504535a00b3757d24df6d1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/025e768a51504535a00b3757d24df6d1"}}, "title": "Prenylated Flavonoids from the Roots of Tephrosia rhodesica.", "authors": [{"family": "Atilaw", "given": "Yoseph", "initials": "Y"}, {"family": "Muiva-Mutisya", "given": "Lois", "initials": "L"}, {"family": "Bogaerts", "given": "Jonathan", "initials": "J"}, {"family": "Duffy", "given": "Sandra", "initials": "S"}, {"family": "Valkonen", "given": "Arto", "initials": "A", "orcid": "0000-0003-2806-3807", "researcher": {"href": "https://publications.scilifelab.se/researcher/ab27a4a2b3da4f85a4068024ae0bd4ca.json"}}, {"family": "Heydenreich", "given": "Matthias", "initials": "M"}, {"family": "Avery", "given": "Vicky M", "initials": "VM"}, {"family": "Rissanen", "given": "Kari", "initials": "K", "orcid": "0000-0002-7282-8419", "researcher": {"href": "https://publications.scilifelab.se/researcher/0fbf32c0cbe34b069a07be5e23a3e638.json"}}, {"family": "Erd\u00e9lyi", "given": "M\u00e1t\u00e9", "initials": "M", "orcid": "0000-0003-0359-5970", "researcher": {"href": "https://publications.scilifelab.se/researcher/f772b571449e417ca6fda2eee361a0c3.json"}}, {"family": "Yenesew", "given": "Abiy", "initials": "A"}], "type": "journal article", "published": "2020-08-28", "journal": {"title": "J. Nat. Prod.", "issn": "1520-6025", "volume": "83", "issue": "8", "pages": "2390-2398", "issn-l": "0163-3864"}, "abstract": "Five new compounds-rhodimer (1), rhodiflavan A (2), rhodiflavan B (3), rhodiflavan C (4), and rhodacarpin (5)-along with 16 known secondary metabolites, were isolated from the CH2Cl2-CH3OH (1:1) extract of the roots of Tephrosia rhodesica. They were identified by NMR spectroscopic, mass spectrometric, X-ray crystallographic, and ECD spectroscopic analyses. The crude extract and the isolated compounds 2-5, 9, 15, and 21 showed activity (100% at 10 \u03bcg and IC50 = 5-15 \u03bcM) against the chloroquine-sensitive (3D7) strain of Plasmodium falciparum.", "doi": "10.1021/acs.jnatprod.0c00245", "pmid": "32790306", "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7460544"}], "notes": [], "created": "2023-05-31T16:25:54.732Z", "modified": "2025-10-17T13:03:56.647Z"}, {"entity": "publication", "iuid": "a4b22326ad624507868b05ce1ce81449", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a4b22326ad624507868b05ce1ce81449.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a4b22326ad624507868b05ce1ce81449"}}, "title": "Bulk-Processed Pd Nanocube\u2013Poly(methyl methacrylate) Nanocomposites as Plasmonic Plastics for Hydrogen Sensing", "authors": [{"family": "Darmadi", "given": "Iwan", "initials": "I", "orcid": "0000-0002-5921-9336", "researcher": {"href": "https://publications.scilifelab.se/researcher/d24542fa29854812a58bc1906bdeaf8a.json"}}, {"family": "Stola\u015b", "given": "Alicja", "initials": "A", "orcid": "0000-0002-6736-9553", "researcher": {"href": "https://publications.scilifelab.se/researcher/f882b7702b204bc88c1e7a81b9554194.json"}}, {"family": "\u00d6stergren", "given": "Ida", "initials": "I"}, {"family": "Berke", "given": "Barbara", "initials": "B", "orcid": "0000-0002-3105-2036", "researcher": {"href": "https://publications.scilifelab.se/researcher/b7e866bd004143959951261606413e8f.json"}}, {"family": "Nugroho", "given": "Ferry Anggoro Ardy", "initials": "FAA", "orcid": "0000-0001-5571-0454", "researcher": {"href": "https://publications.scilifelab.se/researcher/199aa547e4154722a89bd54cb072b3d4.json"}}, {"family": "Minelli", "given": "Matteo", "initials": "M", "orcid": "0000-0003-4662-1526", "researcher": {"href": "https://publications.scilifelab.se/researcher/44301a57b0704c90b546a7ef985dd73e.json"}}, {"family": "Lerch", "given": "Sarah", "initials": "S", "orcid": "0000-0001-5968-8178", "researcher": {"href": "https://publications.scilifelab.se/researcher/e192f96f7cb74b96985567fa2c099bf1.json"}}, {"family": "Tanyeli", "given": "Irem", "initials": "I", "orcid": "0000-0002-5433-2524", "researcher": {"href": "https://publications.scilifelab.se/researcher/ef5582c8609543d3a79f54d0948f3829.json"}}, {"family": "Lund", "given": "Anja", "initials": "A"}, {"family": "Andersson", "given": "Olof", "initials": "O"}, {"family": "Zhdanov", "given": "Vladimir P", "initials": "VP"}, {"family": "Liebi", "given": "Marianne", "initials": "M", "orcid": "0000-0002-5403-0593", "researcher": {"href": "https://publications.scilifelab.se/researcher/a404e64ffe7c47e0ac15819102c38279.json"}}, {"family": "Moth-Poulsen", "given": "Kasper", "initials": "K", "orcid": "0000-0003-4018-4927", "researcher": {"href": "https://publications.scilifelab.se/researcher/5807cc241ba24cf4a7841086d72dc3b9.json"}}, {"family": "M\u00fcller", "given": "Christian", "initials": "C", "orcid": "0000-0001-7859-7909", "researcher": {"href": "https://publications.scilifelab.se/researcher/7fc06198eb0c4a3eb17d052d8ef124ae.json"}}, {"family": "Langhammer", "given": "Christoph", "initials": "C", "orcid": "0000-0003-2180-1379", "researcher": {"href": "https://publications.scilifelab.se/researcher/17178716c3964e53933ddacffe70cc9a.json"}}], "type": "journal-article", "published": "2020-08-28", "journal": {"title": "ACS Appl. Nano Mater.", "issn": "2574-0970", "volume": "3", "issue": "8", "pages": "8438-8445", "issn-l": null}, "abstract": null, "doi": "10.1021/acsanm.0c01907", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2023-02-16T08:06:16.750Z", "modified": "2023-06-19T13:38:29.309Z"}, {"entity": "publication", "iuid": "d90eae148c4e4df49076698b912705f4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d90eae148c4e4df49076698b912705f4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d90eae148c4e4df49076698b912705f4"}}, "title": "High-Throughput Sequencing and Unsupervised Analysis of Formyltetrahydrofolate Synthetase (FTHFS) Gene Amplicons to Estimate Acetogenic Community Structure.", "authors": [{"family": "Singh", "given": "Abhijeet", "initials": "A"}, {"family": "Nylander", "given": "Johan A A", "initials": "JAA"}, {"family": "Schn\u00fcrer", "given": "Anna", "initials": "A"}, {"family": "Bongcam-Rudloff", "given": "Erik", "initials": "E"}, {"family": "M\u00fcller", "given": "Bettina", "initials": "B"}], "type": "journal article", "published": "2020-08-27", "journal": {"title": "Front Microbiol", "issn": "1664-302X", "volume": "11", "issue": null, "pages": "2066", "issn-l": "1664-302X"}, "abstract": "The formyltetrahydrofolate synthetase (FTHFS) gene is a molecular marker of choice to study the diversity of acetogenic communities. However, current analyses are limited due to lack of a high-throughput sequencing approach for FTHFS gene amplicons and a dedicated bioinformatics pipeline for data analysis, including taxonomic annotation and visualization of the sequence data. In the present study, we combined the barcode approach for multiplexed sequencing with unsupervised data analysis to visualize acetogenic community structure. We used samples from a biogas digester to develop proof-of-principle for our combined approach. We successfully generated high-throughput sequence data for the partial FTHFS gene and performed unsupervised data analysis using the novel bioinformatics pipeline \"AcetoScan\" presented in this study, which resulted in taxonomically annotated OTUs, phylogenetic tree, abundance plots and diversity indices. The results demonstrated that high-throughput sequencing can be used to sequence the FTHFS amplicons from a pool of samples, while the analysis pipeline AcetoScan can be reliably used to process the raw sequence data and visualize acetogenic community structure. The method and analysis pipeline described in this paper can assist in the identification and quantification of known or potentially new acetogens. The AcetoScan pipeline is freely available at https://github.com/abhijeetsingh1704/AcetoScan.", "doi": "10.3389/fmicb.2020.02066", "pmid": "32983047", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC7481360"}], "notes": [], "created": "2020-09-10T10:20:24.309Z", "modified": "2024-01-16T13:48:41.857Z"}, {"entity": "publication", "iuid": "e86d241e17894bde94ff435f5c2ff8fa", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e86d241e17894bde94ff435f5c2ff8fa.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e86d241e17894bde94ff435f5c2ff8fa"}}, "title": "Four SARS-CoV-2 Genome Sequences from Late April in Stockholm, Sweden, Reveal a Rare Mutation in the Spike Protein.", "authors": [{"family": "Soratto", "given": "Tatiany Aparecida Teixeira", "initials": "TAT", "orcid": "0000-0001-6263-6432", "researcher": {"href": "https://publications.scilifelab.se/researcher/2de2acb9e872401384dfb70eaadfb88c.json"}}, {"family": "Darban", "given": "Hamid", "initials": "H"}, {"family": "Bjerkner", "given": "Annelie", "initials": "A"}, {"family": "Coorens", "given": "Maarten", "initials": "M"}, {"family": "Albert", "given": "Jan", "initials": "J"}, {"family": "Allander", "given": "Tobias", "initials": "T"}, {"family": "Andersson", "given": "Bj\u00f6rn", "initials": "B"}], "type": "journal article", "published": "2020-08-27", "journal": {"title": "Microbiol Resour Announc", "issn": "2576-098X", "volume": "9", "issue": "35", "issn-l": "2576-098X"}, "abstract": "Here, we report four coding-complete severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome sequences from Stockholm, Sweden, sampled in late April 2020. A rare variant at bp 23463 of the SARS-CoV-2 genome was found, which corresponds to the S1 subunit of the spike protein, changing an arginine (R) residue to histidine (H).", "doi": "10.1128/MRA.00934-20", "pmid": "32855259", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "9/35/e00934-20"}, {"db": "pmc", "key": "PMC7453295"}], "notes": [], "created": "2020-12-07T16:27:03.521Z", "modified": "2024-01-16T13:48:41.868Z"}, {"entity": "publication", "iuid": "acb48c2531964cb4b5a8c73639e2f114", "links": {"self": {"href": "https://publications.scilifelab.se/publication/acb48c2531964cb4b5a8c73639e2f114.json"}, "display": {"href": "https://publications.scilifelab.se/publication/acb48c2531964cb4b5a8c73639e2f114"}}, "title": "Cell-surface receptors enable perception of extracellular cytokinins.", "authors": [{"family": "Antoniadi", "given": "Ioanna", "initials": "I", "orcid": "0000-0001-9053-2788", "researcher": {"href": "https://publications.scilifelab.se/researcher/60bcbb474ded4df08079520c92de49bf.json"}}, {"family": "Nov\u00e1k", "given": "Ond\u0159ej", "initials": "O", "orcid": "0000-0003-3452-0154", "researcher": {"href": "https://publications.scilifelab.se/researcher/8c19165acb9a4ff79dd96af7fccdc5f8.json"}}, {"family": "Gelov\u00e1", "given": "Zuzana", "initials": "Z", "orcid": "0000-0003-4783-1752", "researcher": {"href": "https://publications.scilifelab.se/researcher/afc862721b52467aa092f0ecf9fc7bed.json"}}, {"family": "Johnson", "given": "Alexander", "initials": "A", "orcid": "0000-0002-2739-8843", "researcher": {"href": "https://publications.scilifelab.se/researcher/c9414092144944429b428466733e6567.json"}}, {"family": "Pl\u00edhal", "given": "Ond\u0159ej", "initials": "O", "orcid": "0000-0003-0645-2019", "researcher": {"href": "https://publications.scilifelab.se/researcher/f42115be2a6b4268a3bf6f9200479f93.json"}}, {"family": "Simersk\u00fd", "given": "Radim", "initials": "R", "orcid": "0000-0002-4481-6680", "researcher": {"href": "https://publications.scilifelab.se/researcher/218c11787cf2467a98ab7d0c826de187.json"}}, {"family": "Mik", "given": "V\u00e1clav", "initials": "V", "orcid": "0000-0002-8515-3035", "researcher": {"href": "https://publications.scilifelab.se/researcher/51f69a95dba24bd793e708f0cdcc2ded.json"}}, {"family": "Vain", "given": "Thomas", "initials": "T"}, {"family": "Mateo-Bonmat\u00ed", "given": "Eduardo", "initials": "E", "orcid": "0000-0002-2364-5173", "researcher": {"href": "https://publications.scilifelab.se/researcher/f1e96edf1a914d2f8ea8eb46c3ebacc4.json"}}, {"family": "Karady", "given": "Michal", "initials": "M"}, {"family": "Pernisov\u00e1", "given": "Mark\u00e9ta", "initials": "M", "orcid": "0000-0002-5803-2879", "researcher": {"href": "https://publications.scilifelab.se/researcher/acc243598b74495999230f9b1b0da0be.json"}}, {"family": "Pla\u010dkov\u00e1", "given": "Lenka", "initials": "L"}, {"family": "Opassathian", "given": "Korawit", "initials": "K"}, {"family": "Hej\u00e1tko", "given": "Jan", "initials": "J"}, {"family": "Robert", "given": "St\u00e9phanie", "initials": "S", "orcid": "0000-0002-0013-3239", "researcher": {"href": "https://publications.scilifelab.se/researcher/74a96c43520f4c9c91e44be8a7d39e6c.json"}}, {"family": "Friml", "given": "Ji\u0159\u00ed", "initials": "J", "orcid": "0000-0002-8302-7596", "researcher": {"href": "https://publications.scilifelab.se/researcher/6e525fe6afc5490a86223e38be195cee.json"}}, {"family": "Dole\u017eal", "given": "Karel", "initials": "K", "orcid": "0000-0003-4938-0350", "researcher": {"href": "https://publications.scilifelab.se/researcher/f209cf1d8e5d4945b81bd9f01c2b2665.json"}}, {"family": "Ljung", "given": "Karin", "initials": "K", "orcid": "0000-0003-2901-189X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f91b1e1f90c24559b915ebcd265804a4.json"}}, {"family": "Turnbull", "given": "Colin", "initials": "C", "orcid": "0000-0001-6635-1418", "researcher": {"href": "https://publications.scilifelab.se/researcher/abd75adef49f4c789b69206cdb7e8cf0.json"}}], "type": "journal article", "published": "2020-08-27", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "11", "issue": "1", "pages": "4284", "issn-l": "2041-1723"}, "abstract": "Cytokinins are mobile multifunctional plant hormones with roles in development and stress resilience. Although their Histidine Kinase receptors are substantially localised to the endoplasmic reticulum, cellular sites of cytokinin perception and importance of spatially heterogeneous cytokinin distribution continue to be debated. Here we show that cytokinin perception by plasma membrane receptors is an effective additional path for cytokinin response. Readout from a Two Component Signalling cytokinin-specific reporter (TCSn::GFP) closely matches intracellular cytokinin content in roots, yet we also find cytokinins in extracellular fluid, potentially enabling action at the cell surface. Cytokinins covalently linked to beads that could not pass the plasma membrane increased expression of both TCSn::GFP and Cytokinin Response Factors. Super-resolution microscopy of GFP-labelled receptors and diminished TCSn::GFP response to immobilised cytokinins in cytokinin receptor mutants, further indicate that receptors can function at the cell surface. We argue that dual intracellular and surface locations may augment flexibility of cytokinin responses.", "doi": "10.1038/s41467-020-17700-9", "pmid": "32855409", "labels": {"Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-17700-9"}, {"db": "pmc", "key": "PMC7453015"}], "notes": [], "created": "2020-12-11T11:56:05.497Z", "modified": "2025-10-17T13:03:16.685Z"}, {"entity": "publication", "iuid": "94f294cb977c40bfa353d86973dd9eb8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/94f294cb977c40bfa353d86973dd9eb8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/94f294cb977c40bfa353d86973dd9eb8"}}, "title": "\u00b5 Opioid Receptor Agonism for L-DOPA-Induced Dyskinesia in Parkinson's Disease.", "authors": [{"family": "Bezard", "given": "Erwan", "initials": "E", "orcid": "0000-0002-0410-4638", "researcher": {"href": "https://publications.scilifelab.se/researcher/c33e3029113549ea96e60c7952e5a19a.json"}}, {"family": "Li", "given": "Qin", "initials": "Q"}, {"family": "Hulme", "given": "Heather", "initials": "H"}, {"family": "Fridjonsdottir", "given": "Elva", "initials": "E"}, {"family": "Nilsson", "given": "Anna", "initials": "A"}, {"family": "Pioli", "given": "Elsa", "initials": "E"}, {"family": "Andren", "given": "Per E", "initials": "PE"}, {"family": "Crossman", "given": "Alan R", "initials": "AR"}], "type": "journal article", "published": "2020-08-26", "journal": {"title": "J. Neurosci.", "issn": "1529-2401", "volume": "40", "issue": "35", "pages": "6812-6819", "issn-l": "0270-6474"}, "abstract": "Parkinson's disease (PD) is characterized by severe locomotor deficits and is commonly treated with the dopamine precursor L-DOPA, but its prolonged usage causes dyskinesias referred to as L-DOPA-induced dyskinesia (LID). Several studies in animal models of PD have suggested that dyskinesias are associated with a heightened opioid cotransmitter tone, observations that have led to the notion of a LID-related hyperactive opioid transmission that should be corrected by \u00b5 opioid receptor antagonists. Reports that both antagonists and agonists of the \u00b5 opioid receptor may alleviate LID severity in primate models of PD and LID, together with the failure of nonspecific antagonist to improve LID in pilot clinical trials in patients, raises doubt about the reliability of the available data on the opioid system in PD and LID. After in vitro characterization of the functional activity at the \u00b5 opioid receptor, we selected prototypical agonists, antagonists, and partial agonists at the \u00b5 opioid receptor. We then showed that both oral and discrete intracerebral administration of a \u00b5 receptor agonist, but not of an antagonist as long thought, ameliorated LIDs in the gold-standard bilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned female macaque model of PD and LID. The results call for a reappraisal of opioid pharmacology in the basal ganglia as well as for the development of brain nucleus-targeted \u00b5 opioid receptor agonists.SIGNIFICANCE STATEMENT \u00b5 opioid receptors have long been considered as a viable target for alleviating the severity of L-DOPA-induced hyperkinetic side effects, induced by the chronic treatment of Parkinson's disease motor symptoms with L-DOPA. Conflicting results between experimental parkinsonism and Parkinson's disease patients, however, dampened the enthusiasm for the target. Here we reappraise the pharmacology and then demonstrate that both oral and discrete intracerebral administration of a \u00b5 receptor agonist, but not of an antagonist as long thought, ameliorates LIDs in the gold-standard bilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned macaque model of Parkinson's disease, calling for a reappraisal of the opioid pharmacology as well as for the development of brain nucleus-targeted \u00b5 receptor agonists.", "doi": "10.1523/JNEUROSCI.0610-20.2020", "pmid": "32690616", "labels": {"Spatial Mass Spectrometry": "Collaborative"}, "xrefs": [{"db": "pii", "key": "JNEUROSCI.0610-20.2020"}, {"db": "pmc", "key": "PMC7455220"}], "notes": [], "created": "2021-03-26T12:45:05.245Z", "modified": "2021-12-03T11:51:13.509Z"}, {"entity": "publication", "iuid": "aad98531594443b3bdf72d5748622b1e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/aad98531594443b3bdf72d5748622b1e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/aad98531594443b3bdf72d5748622b1e"}}, "title": "Combined transcriptome and proteome profiling of the pancreatic \u03b2-cell response to palmitate unveils key pathways of \u03b2-cell lipotoxicity.", "authors": [{"family": "Lytrivi", "given": "Maria", "initials": "M"}, {"family": "Ghaddar", "given": "Kassem", "initials": "K"}, {"family": "Lopes", "given": "Miguel", "initials": "M"}, {"family": "Rosengren", "given": "Victoria", "initials": "V"}, {"family": "Piron", "given": "Anthony", "initials": "A"}, {"family": "Yi", "given": "Xiaoyan", "initials": "X"}, {"family": "Johansson", "given": "Henrik", "initials": "H"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Igoillo-Esteve", "given": "Mariana", "initials": "M"}, {"family": "Cunha", "given": "Daniel A", "initials": "DA"}, {"family": "Marselli", "given": "Lorella", "initials": "L"}, {"family": "Marchetti", "given": "Piero", "initials": "P"}, {"family": "Orts\u00e4ter", "given": "Henrik", "initials": "H"}, {"family": "Eizirik", "given": "Decio L", "initials": "DL"}, {"family": "Cnop", "given": "Miriam", "initials": "M", "orcid": "0000-0002-5112-1692", "researcher": {"href": "https://publications.scilifelab.se/researcher/b0d855a049344a42bbb571e7c8e688b0.json"}}], "type": "journal article", "published": "2020-08-26", "journal": {"title": "BMC Genomics", "issn": "1471-2164", "volume": "21", "issue": "1", "pages": "590", "issn-l": "1471-2164"}, "abstract": "Prolonged exposure to elevated free fatty acids induces \u03b2-cell failure (lipotoxicity) and contributes to the pathogenesis of type 2 diabetes. In vitro exposure of \u03b2-cells to the saturated free fatty acid palmitate is a valuable model of lipotoxicity, reproducing features of \u03b2-cell failure observed in type 2 diabetes. In order to map the \u03b2-cell response to lipotoxicity, we combined RNA-sequencing of palmitate-treated human islets with iTRAQ proteomics of insulin-secreting INS-1E cells following a time course exposure to palmitate.\n\nCrossing transcriptome and proteome of palmitate-treated \u03b2-cells revealed 85 upregulated and 122 downregulated genes at both transcript and protein level. Pathway analysis identified lipid metabolism, oxidative stress, amino-acid metabolism and cell cycle pathways among the most enriched palmitate-modified pathways. Palmitate induced gene expression changes compatible with increased free fatty acid mitochondrial import and \u03b2-oxidation, decreased lipogenesis and modified cholesterol transport. Palmitate modified genes regulating endoplasmic reticulum (ER) function, ER-to-Golgi transport and ER stress pathways. Furthermore, palmitate modulated cAMP/protein kinase A (PKA) signaling, inhibiting expression of PKA anchoring proteins and downregulating the GLP-1 receptor. SLC7 family amino-acid transporters were upregulated in response to palmitate but this induction did not contribute to \u03b2-cell demise. To unravel critical mediators of lipotoxicity upstream of the palmitate-modified genes, we identified overrepresented transcription factor binding sites and performed network inference analysis. These identified LXR, PPAR\u03b1, FOXO1 and BACH1 as key transcription factors orchestrating the metabolic and oxidative stress responses to palmitate.\n\nThis is the first study to combine transcriptomic and sensitive time course proteomic profiling of palmitate-exposed \u03b2-cells. Our results provide comprehensive insight into gene and protein expression changes, corroborating and expanding beyond previous findings. The identification of critical drivers and pathways of the \u03b2-cell lipotoxic response points to novel therapeutic targets for type 2 diabetes.", "doi": "10.1186/s12864-020-07003-0", "pmid": "32847508", "labels": {"Global Proteomics and Proteogenomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1186/s12864-020-07003-0"}, {"db": "pmc", "key": "PMC7448506"}], "notes": [], "created": "2021-01-12T18:17:43.722Z", "modified": "2021-11-10T12:48:00.690Z"}, {"entity": "publication", "iuid": "9ca42c9a52d44cd99374572d2643ad5a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9ca42c9a52d44cd99374572d2643ad5a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9ca42c9a52d44cd99374572d2643ad5a"}}, "title": "Systems-Level Immunomonitoring from Acute to Recovery Phase of Severe COVID-19.", "authors": [{"family": "Rodriguez", "given": "Lucie", "initials": "L"}, {"family": "Pekkarinen", "given": "Pirkka T", "initials": "PT"}, {"family": "Lakshmikanth", "given": "Tadepally", "initials": "T", "orcid": "0000-0001-7256-5770", "researcher": {"href": "https://publications.scilifelab.se/researcher/92e81aa6b0cf4ff0a18b14098bf0fcc1.json"}}, {"family": "Tan", "given": "Ziyang", "initials": "Z"}, {"family": "Consiglio", "given": "Camila Rosat", "initials": "CR"}, {"family": "Pou", "given": "Christian", "initials": "C"}, {"family": "Chen", "given": "Yang", "initials": "Y"}, {"family": "Mugabo", "given": "Constantin Habimana", "initials": "CH"}, {"family": "Nguyen", "given": "Ngoc Anh", "initials": "NA", "orcid": "0000-0003-3367-8048", "researcher": {"href": "https://publications.scilifelab.se/researcher/ba8cb2f13825449f9892570cc2793964.json"}}, {"family": "Nowlan", "given": "Kirsten", "initials": "K"}, {"family": "Strandin", "given": "Tomas", "initials": "T"}, {"family": "Levanov", "given": "Lev", "initials": "L"}, {"family": "Mikes", "given": "Jaromir", "initials": "J", "orcid": "0000-0002-9941-7855", "researcher": {"href": "https://publications.scilifelab.se/researcher/21c127bffa7c4a01af7fad8ba6bac90b.json"}}, {"family": "Wang", "given": "Jun", "initials": "J"}, {"family": "Kantele", "given": "Anu", "initials": "A"}, {"family": "Hepojoki", "given": "Jussi", "initials": "J", "orcid": "0000-0001-5699-214X", "researcher": {"href": "https://publications.scilifelab.se/researcher/90f4bea163f34c08ade5950650ef9566.json"}}, {"family": "Vapalahti", "given": "Olli", "initials": "O", "orcid": "0000-0003-2270-6824", "researcher": {"href": "https://publications.scilifelab.se/researcher/ddd242b27ab54495aa9e135590938eaf.json"}}, {"family": "Heinonen", "given": "Santtu", "initials": "S"}, {"family": "Kek\u00e4l\u00e4inen", "given": "Eliisa", "initials": "E"}, {"family": "Brodin", "given": "Petter", "initials": "P", "orcid": "0000-0002-8103-0046", "researcher": {"href": "https://publications.scilifelab.se/researcher/40097353cdb24e52bf2330eb687042bf.json"}}], "type": "journal article", "published": "2020-08-25", "journal": {"title": "Cell Reports Medicine", "issn": "2666-3791", "issn-l": "2666-3791", "volume": "1", "issue": "5", "pages": "100078"}, "abstract": "Severe disease of SARS-CoV-2 is characterized by vigorous inflammatory responses in the lung, often with a sudden onset after 5-7 days of stable disease. Efforts to modulate this hyperinflammation and the associated acute respiratory distress syndrome rely on the unraveling of the immune cell interactions and cytokines that drive such responses. Given that every patient is captured at different stages of infection, longitudinal monitoring of the immune response is critical and systems-level analyses are required to capture cellular interactions. Here, we report on a systems-level blood immunomonitoring study of 37 adult patients diagnosed with COVID-19 and followed with up to 14 blood samples from acute to recovery phases of the disease. We describe an IFN\u03b3-eosinophil axis activated before lung hyperinflammation and changes in cell-cell co-regulation during different stages of the disease. We also map an immune trajectory during recovery that is shared among patients with severe COVID-19.", "doi": "10.1016/j.xcrm.2020.100078", "pmid": "32838342", "labels": {"Affinity Proteomics Stockholm": "Service", "Cellular Immunomonitoring": "Technology development", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S2666-3791(20)30099-9"}, {"db": "pii", "key": "100078"}, {"db": "pmc", "key": "PMC7405891"}], "notes": [], "created": "2020-08-10T15:24:35.789Z", "modified": "2024-01-16T13:48:41.879Z"}, {"entity": "publication", "iuid": "be6dfc07d42b41648f42432ddcda8787", "links": {"self": {"href": "https://publications.scilifelab.se/publication/be6dfc07d42b41648f42432ddcda8787.json"}, "display": {"href": "https://publications.scilifelab.se/publication/be6dfc07d42b41648f42432ddcda8787"}}, "title": "Whole-genome sequencing and gene network modules predict gemcitabine/carboplatin-induced myelosuppression in non-small cell lung cancer patients.", "authors": [{"family": "Bj\u00f6rn", "given": "Niclas", "initials": "N", "orcid": "0000-0001-6806-4527", "researcher": {"href": "https://publications.scilifelab.se/researcher/a39cecc1714f4331b08a47f1f1bbe7ac.json"}}, {"family": "Badam", "given": "Tejaswi Venkata Satya", "initials": "TVS", "orcid": "0000-0002-6719-4861", "researcher": {"href": "https://publications.scilifelab.se/researcher/9e4b28972942434fba0d715354352267.json"}}, {"family": "Spalinskas", "given": "Rapolas", "initials": "R", "orcid": "0000-0002-1648-6426", "researcher": {"href": "https://publications.scilifelab.se/researcher/18ca0b7337b849a49861aedf2971067e.json"}}, {"family": "Brand\u00e9n", "given": "Eva", "initials": "E"}, {"family": "Koyi", "given": "Hirsh", "initials": "H", "orcid": "0000-0001-5797-7873", "researcher": {"href": "https://publications.scilifelab.se/researcher/020d1b7e7693495484dc85c4ba6f2adc.json"}}, {"family": "Lewensohn", "given": "Rolf", "initials": "R"}, {"family": "De Petris", "given": "Luigi", "initials": "L"}, {"family": "Lubovac-Pilav", "given": "Zelmina", "initials": "Z", "orcid": "0000-0001-6427-0315", "researcher": {"href": "https://publications.scilifelab.se/researcher/af98c65fa2964875bd6d46f9c2488e6b.json"}}, {"family": "Sahl\u00e9n", "given": "Pelin", "initials": "P"}, {"family": "Lundeberg", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4313-1601", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a4e6ca0f29b4ead8569e2729481c3e0.json"}}, {"family": "Gustafsson", "given": "Mika", "initials": "M", "orcid": "0000-0002-0048-4063", "researcher": {"href": "https://publications.scilifelab.se/researcher/466661ecb9274ecc8f1a832b95ef19b2.json"}}, {"family": "Gr\u00e9en", "given": "Henrik", "initials": "H"}], "type": "journal article", "published": "2020-08-24", "journal": {"title": "npj Syst Biol Appl", "issn": "2056-7189", "volume": "6", "issue": "1", "pages": "25", "issn-l": "2056-7189"}, "abstract": "Gemcitabine/carboplatin chemotherapy commonly induces myelosuppression, including neutropenia, leukopenia, and thrombocytopenia. Predicting patients at risk of these adverse drug reactions (ADRs) and adjusting treatments accordingly is a long-term goal of personalized medicine. This study used whole-genome sequencing (WGS) of blood samples from 96 gemcitabine/carboplatin-treated non-small cell lung cancer (NSCLC) patients and gene network modules for predicting myelosuppression. Association of genetic variants in PLINK found 4594, 5019, and 5066 autosomal SNVs/INDELs with p \u2264 1 \u00d7 10-3 for neutropenia, leukopenia, and thrombocytopenia, respectively. Based on the SNVs/INDELs we identified the toxicity module, consisting of 215 unique overlapping genes inferred from MCODE-generated gene network modules of 350, 345, and 313 genes, respectively. These module genes showed enrichment for differentially expressed genes in rat bone marrow, human bone marrow, and human cell lines exposed to carboplatin and gemcitabine (p < 0.05). Then using 80% of the patients as training data, random LASSO reduced the number of SNVs/INDELs in the toxicity module into a feasible prediction model consisting of 62 SNVs/INDELs that accurately predict both the training and the test (remaining 20%) data with high (CTCAE 3-4) and low (CTCAE 0-1) maximal myelosuppressive toxicity completely, with the receiver-operating characteristic (ROC) area under the curve (AUC) of 100%. The present study shows how WGS, gene network modules, and random LASSO can be used to develop a feasible and tested model for predicting myelosuppressive toxicity. Although the proposed model predicts myelosuppression in this study, further evaluation in other studies is required to determine its reproducibility, usability, and clinical effect.", "doi": "10.1038/s41540-020-00146-6", "pmid": "32839457", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41540-020-00146-6"}, {"db": "pmc", "key": "PMC7445166"}], "notes": [], "created": "2020-12-07T16:27:04.771Z", "modified": "2024-01-16T13:48:41.889Z"}, {"entity": "publication", "iuid": "6f59a84f1afe4e30bd4fb89e91d3311d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6f59a84f1afe4e30bd4fb89e91d3311d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6f59a84f1afe4e30bd4fb89e91d3311d"}}, "title": "Single cell RNA sequencing identifies early diversity of sensory neurons forming via bi-potential intermediates.", "authors": [{"family": "Faure", "given": "Louis", "initials": "L", "orcid": "0000-0003-4621-586X", "researcher": {"href": "https://publications.scilifelab.se/researcher/bbf218e53c854d69a1b474a61480c33f.json"}}, {"family": "Wang", "given": "Yiqiao", "initials": "Y"}, {"family": "Kastriti", "given": "Maria Eleni", "initials": "ME", "orcid": "0000-0002-0563-7399", "researcher": {"href": "https://publications.scilifelab.se/researcher/9e0722d8c5484a13bb37c3a3b084ff8c.json"}}, {"family": "Fontanet", "given": "Paula", "initials": "P", "orcid": "0000-0002-5324-6077", "researcher": {"href": "https://publications.scilifelab.se/researcher/dfe102480cb7458a941fc70fe7f5cb9b.json"}}, {"family": "Cheung", "given": "Kylie K Y", "initials": "KKY"}, {"family": "Petitpr\u00e9", "given": "Charles", "initials": "C"}, {"family": "Wu", "given": "Haohao", "initials": "H"}, {"family": "Sun", "given": "Lynn Linyu", "initials": "LL"}, {"family": "Runge", "given": "Karen", "initials": "K"}, {"family": "Croci", "given": "Laura", "initials": "L", "orcid": "0000-0002-7826-428X", "researcher": {"href": "https://publications.scilifelab.se/researcher/5e08f8646894441297506e2a3eb5fb57.json"}}, {"family": "Landy", "given": "Mark A", "initials": "MA", "orcid": "0000-0002-2789-0774", "researcher": {"href": "https://publications.scilifelab.se/researcher/5334230675f543fc8b870741f103854d.json"}}, {"family": "Lai", "given": "Helen C", "initials": "HC", "orcid": "0000-0003-4334-0243", "researcher": {"href": "https://publications.scilifelab.se/researcher/de71bea36e954743b1e576c7e681f9eb.json"}}, {"family": "Consalez", "given": "Gian Giacomo", "initials": "GG"}, {"family": "de Chevigny", "given": "Antoine", "initials": "A", "orcid": "0000-0002-7413-0591", "researcher": {"href": "https://publications.scilifelab.se/researcher/0a2d23fc97564742905b48e36f4bc585.json"}}, {"family": "Lallemend", "given": "Fran\u00e7ois", "initials": "F"}, {"family": "Adameyko", "given": "Igor", "initials": "I", "orcid": "0000-0001-5471-0356", "researcher": {"href": "https://publications.scilifelab.se/researcher/346f484a56cb4ad5b866b194ccd44e4f.json"}}, {"family": "Hadjab", "given": "Saida", "initials": "S", "orcid": "0000-0001-7953-8396", "researcher": {"href": "https://publications.scilifelab.se/researcher/ed79ab77088f43859e11b75dcae33d73.json"}}], "type": "journal article", "published": "2020-08-21", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "11", "issue": "1", "pages": "4175", "issn-l": "2041-1723"}, "abstract": "Somatic sensation is defined by the existence of a diversity of primary sensory neurons with unique biological features and response profiles to external and internal stimuli. However, there is no coherent picture about how this diversity of cell states is transcriptionally generated. Here, we use deep single cell analysis to resolve fate splits and molecular biasing processes during sensory neurogenesis in mice. Our results identify a complex series of successive and specific transcriptional changes in post-mitotic neurons that delineate hierarchical regulatory states leading to the generation of the main sensory neuron classes. In addition, our analysis identifies previously undetected early gene modules expressed long before fate determination although being clearly associated with defined sensory subtypes. Overall, the early diversity of sensory neurons is generated through successive bi-potential intermediates in which synchronization of relevant gene modules and concurrent repression of competing fate programs precede cell fate stabilization and final commitment.", "doi": "10.1038/s41467-020-17929-4", "pmid": "32826903", "labels": {"Eukaryotic Single Cell Genomics (ESCG)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-17929-4"}, {"db": "pmc", "key": "PMC7442800"}], "notes": [], "created": "2020-10-06T11:10:56.370Z", "modified": "2024-01-16T13:48:41.901Z"}, {"entity": "publication", "iuid": "8b20bf8ea1c64b27b9926d89b98d064b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8b20bf8ea1c64b27b9926d89b98d064b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8b20bf8ea1c64b27b9926d89b98d064b"}}, "title": "Natural killer cell immunotypes related to COVID-19 disease severity.", "authors": [{"family": "Maucourant", "given": "Christopher", "initials": "C", "orcid": "0000-0003-1033-2992", "researcher": {"href": "https://publications.scilifelab.se/researcher/8221b644c8a841fca76d35e19b7e61e8.json"}}, {"family": "Filipovic", "given": "Iva", "initials": "I", "orcid": "0000-0002-8166-5500", "researcher": {"href": "https://publications.scilifelab.se/researcher/cfe34a0a54954684bd1e405afd479ab3.json"}}, {"family": "Ponzetta", "given": "Andrea", "initials": "A", "orcid": "0000-0003-3224-802X", "researcher": {"href": "https://publications.scilifelab.se/researcher/8b06c3ab1bae404dba4ec9a1eee4f78b.json"}}, {"family": "Aleman", "given": "Soo", "initials": "S"}, {"family": "Cornillet", "given": "Martin", "initials": "M", "orcid": "0000-0001-7981-0927", "researcher": {"href": "https://publications.scilifelab.se/researcher/aad5c88284e54bd0af1e3ce4004dd24c.json"}}, {"family": "Hertwig", "given": "Laura", "initials": "L", "orcid": "0000-0002-1170-0948", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b64addfb67f4e8b898bbb1ced5f5e77.json"}}, {"family": "Strunz", "given": "Benedikt", "initials": "B"}, {"family": "Lentini", "given": "Antonio", "initials": "A", "orcid": "0000-0003-1239-5495", "researcher": {"href": "https://publications.scilifelab.se/researcher/e282901d24c64b16a540eff0d57776f4.json"}}, {"family": "Reinius", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Brownlie", "given": "Demi", "initials": "D", "orcid": "0000-0001-5932-6425", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e879a6ef8ff45bea049986707480e99.json"}}, {"family": "Cuapio", "given": "Angelica", "initials": "A"}, {"family": "Ask", "given": "Eivind Heggernes", "initials": "EH", "orcid": "0000-0001-8655-1433", "researcher": {"href": "https://publications.scilifelab.se/researcher/f4a3a0f566a342db89c54b87a50d5e5b.json"}}, {"family": "Hull", "given": "Ryan M", "initials": "RM", "orcid": "0000-0001-7153-4198", "researcher": {"href": "https://publications.scilifelab.se/researcher/26f05788ac904e9597ca68f3b3fb5486.json"}}, {"family": "Haroun-Izquierdo", "given": "Alvaro", "initials": "A", "orcid": "0000-0003-4557-3606", "researcher": {"href": "https://publications.scilifelab.se/researcher/ca1f59e2b148496ba53a05d1ee4eb8b2.json"}}, {"family": "Schaffer", "given": "Marie", "initials": "M"}, {"family": "Klingstr\u00f6m", "given": "Jonas", "initials": "J", "orcid": "0000-0001-9076-1441", "researcher": {"href": "https://publications.scilifelab.se/researcher/95c1b345ae434fb383b7fe6a1d053c80.json"}}, {"family": "Folkesson", "given": "Elin", "initials": "E", "orcid": "0000-0002-6585-6235", "researcher": {"href": "https://publications.scilifelab.se/researcher/82777b8f48324c58bcad72799d71fd4a.json"}}, {"family": "Buggert", "given": "Marcus", "initials": "M", "orcid": "0000-0003-0633-1719", "researcher": {"href": "https://publications.scilifelab.se/researcher/9a54e4b5136642eeafa77ac5118a0c81.json"}}, {"family": "Sandberg", "given": "Johan K", "initials": "JK", "orcid": "0000-0002-6275-0750", "researcher": {"href": "https://publications.scilifelab.se/researcher/7468c415a46645a3a4c3d28badcff954.json"}}, {"family": "Eriksson", "given": "Lars I", "initials": "LI"}, {"family": "Rooyackers", "given": "Olav", "initials": "O", "orcid": "0000-0002-3391-5448", "researcher": {"href": "https://publications.scilifelab.se/researcher/52f4fd2e5e204e598aa5087ff3f13680.json"}}, {"family": "Ljunggren", "given": "Hans-Gustaf", "initials": "HG"}, {"family": "Malmberg", "given": "Karl-Johan", "initials": "KJ"}, {"family": "Micha\u00eblsson", "given": "Jakob", "initials": "J"}, {"family": "Marquardt", "given": "Nicole", "initials": "N", "orcid": "0000-0003-3186-4752", "researcher": {"href": "https://publications.scilifelab.se/researcher/b87ccad53d354bdd80af490dc8a0c019.json"}}, {"family": "Hammer", "given": "Quirin", "initials": "Q", "orcid": "0000-0003-2968-6061", "researcher": {"href": "https://publications.scilifelab.se/researcher/3b6b2e5256c8401f83c3f89b5c5bb92f.json"}}, {"family": "Str\u00e5lin", "given": "Kristoffer", "initials": "K", "orcid": "0000-0002-8801-3169", "researcher": {"href": "https://publications.scilifelab.se/researcher/a6ffa1185f4142b7ab7c372c0c139df6.json"}}, {"family": "Bj\u00f6rkstr\u00f6m", "given": "Niklas K", "initials": "NK", "orcid": "0000-0002-0967-076X", "researcher": {"href": "https://publications.scilifelab.se/researcher/bf38521350ae490099f01bda1d10be4c.json"}}, {"family": "Karolinska COVID-19 Study Group", "given": "", "initials": ""}], "type": "journal article", "published": "2020-08-21", "journal": {"title": "Sci Immunol", "issn": "2470-9468", "volume": "5", "issue": "50", "pages": "eabd6832", "issn-l": null}, "abstract": "Understanding innate immune responses in COVID-19 is important to decipher mechanisms of host responses and interpret disease pathogenesis. Natural killer (NK) cells are innate effector lymphocytes that respond to acute viral infections but might also contribute to immunopathology. Using 28-color flow cytometry, we here reveal strong NK cell activation across distinct subsets in peripheral blood of COVID-19 patients. This pattern was mirrored in scRNA-seq signatures of NK cells in bronchoalveolar lavage from COVID-19 patients. Unsupervised high-dimensional analysis of peripheral blood NK cells furthermore identified distinct NK cell immunotypes that were linked to disease severity. Hallmarks of these immunotypes were high expression of perforin, NKG2C, and Ksp37, reflecting increased presence of adaptive NK cells in circulation of patients with severe disease. Finally, arming of CD56bright NK cells was observed across COVID-19 disease states, driven by a defined protein-protein interaction network of inflammatory soluble factors. This study provides a detailed map of the NK cell activation landscape in COVID-19 disease.", "doi": "10.1126/sciimmunol.abd6832", "pmid": "32826343", "labels": {"Affinity Proteomics Stockholm": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "5/50/eabd6832"}, {"db": "pmc", "key": "PMC7665314"}], "notes": [], "created": "2020-12-10T16:30:00.149Z", "modified": "2024-01-16T13:48:41.915Z"}, {"entity": "publication", "iuid": "a39c8226c5cc4a6ca115a111b216aa21", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a39c8226c5cc4a6ca115a111b216aa21.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a39c8226c5cc4a6ca115a111b216aa21"}}, "title": "13q12.2 deletions in acute lymphoblastic leukemia lead to upregulation of FLT3 through enhancer hijacking.", "authors": [{"family": "Yang", "given": "Minjun", "initials": "M", "orcid": "0000-0002-3324-1498", "researcher": {"href": "https://publications.scilifelab.se/researcher/62822d0b9c6c4a01a53829b9b05443ba.json"}}, {"family": "Safavi", "given": "Setareh", "initials": "S"}, {"family": "Woodward", "given": "Eleanor L", "initials": "EL"}, {"family": "Duployez", "given": "Nicolas", "initials": "N", "orcid": "0000-0002-3927-1022", "researcher": {"href": "https://publications.scilifelab.se/researcher/9df1046b96274d8e98efc5c4ba11c4d0.json"}}, {"family": "Olsson-Arvidsson", "given": "Linda", "initials": "L"}, {"family": "Ungerb\u00e4ck", "given": "Jonas", "initials": "J", "orcid": "0000-0002-2190-3896", "researcher": {"href": "https://publications.scilifelab.se/researcher/d8f5ebabd9b541e388d170eb9ecf10fc.json"}}, {"family": "Sigvardsson", "given": "Mikael", "initials": "M"}, {"family": "Zaliova", "given": "Marketa", "initials": "M"}, {"family": "Zuna", "given": "Jan", "initials": "J"}, {"family": "Fioretos", "given": "Thoas", "initials": "T", "orcid": "0000-0002-3235-6154", "researcher": {"href": "https://publications.scilifelab.se/researcher/35a5c1b6023345c6b1317c590bf80680.json"}}, {"family": "Johansson", "given": "Bertil", "initials": "B"}, {"family": "Nord", "given": "Karolin H", "initials": "KH", "orcid": "0000-0002-2397-2254", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a3367cdd2a44c23aad89d176be5b74c.json"}}, {"family": "Paulsson", "given": "Kajsa", "initials": "K", "orcid": "0000-0001-7950-222X", "researcher": {"href": "https://publications.scilifelab.se/researcher/2033b23811f1432c90ad860dd993e7a8.json"}}], "type": "journal article", "published": "2020-08-20", "journal": {"title": "Blood", "issn": "1528-0020", "volume": "136", "issue": "8", "pages": "946-956", "issn-l": "0006-4971"}, "abstract": "Mutations in the FMS-like tyrosine kinase 3 (FLT3) gene in 13q12.2 are among the most common driver events in acute leukemia, leading to increased cell proliferation and survival through activation of the phosphatidylinositol 3-kinase/AKT-, RAS/MAPK-, and STAT5-signaling pathways. In this study, we examine the pathogenetic impact of somatic hemizygous 13q12.2 microdeletions in B-cell precursor (BCP) acute lymphoblastic leukemia (ALL) using 5 different patient cohorts (in total including 1418 cases). The 13q12.2 deletions occur immediately 5' of FLT3 and involve the PAN3 locus. By detailed analysis of the 13q12.2 segment, we show that the deletions lead to loss of a topologically associating domain border and an enhancer of FLT3. This results in increased cis interactions between the FLT3 promoter and another enhancer located distally to the deletion breakpoints, with subsequent allele-specific upregulation of FLT3 expression, expected to lead to ligand-independent activation of the receptor and downstream signaling. The 13q12.2 deletions are highly enriched in the high-hyperdiploid BCP ALL subtype (frequency 3.9% vs 0.5% in other BCP ALL) and in cases that subsequently relapsed. Taken together, our study describes a novel mechanism of FLT3 involvement in leukemogenesis by upregulation via chromatin remodeling and enhancer hijacking. These data further emphasize the role of FLT3 as a driver gene in BCP ALL.", "doi": "10.1182/blood.2019004684", "pmid": "32384149", "labels": {"Clinical Genomics Lund": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7498303"}, {"db": "pii", "key": "S0006-4971(20)61778-5"}], "notes": [], "created": "2020-12-01T18:30:47.513Z", "modified": "2022-11-24T08:39:20.015Z"}, {"entity": "publication", "iuid": "62278042bce741a7830004b9bee7a21c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/62278042bce741a7830004b9bee7a21c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/62278042bce741a7830004b9bee7a21c"}}, "title": "Structural basis of mitochondrial translation", "authors": [{"family": "Aibara", "given": "Shintaro", "initials": "S", "orcid": "0000-0003-2221-482X", "researcher": {"href": "https://publications.scilifelab.se/researcher/d66746c4bec5414da78b2a325a13328f.json"}}, {"family": "Singh", "given": "Vivek", "initials": "V", "orcid": "0000-0003-4656-3362", "researcher": {"href": "https://publications.scilifelab.se/researcher/0576b8ffc93d42f6b47d9d0d7d01bbd0.json"}}, {"family": "Modelska", "given": "Angelika", "initials": "A"}, {"family": "Amunts", "given": "Alexey", "initials": "A", "orcid": "0000-0002-5302-1740", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7d0bf36ad1a47f5b5b88f78d1e15395.json"}}], "type": "journal-article", "published": "2020-08-19", "journal": {"volume": "9", "issn": "2050-084X", "issue": null, "pages": "1-17", "title": "Elife", "issn-l": "2050-084X"}, "abstract": "Translation of mitochondrial messenger RNA (mt-mRNA) is performed by distinct mitoribosomes comprising at least 36 mitochondria-specific proteins. How these mitoribosomal proteins assist in the binding of mt-mRNA and to what extent they are involved in the translocation of transfer RNA (mt-tRNA) is unclear. To visualize the process of translation in human mitochondria, we report ~3.0 \u00c5 resolution structure of the human mitoribosome, including the L7/L12 stalk, and eight structures of its functional complexes with mt-mRNA, mt-tRNAs, recycling factor and additional trans factors. The study reveals a transacting protein module LRPPRC-SLIRP that delivers mt-mRNA to the mitoribosomal small subunit through a dedicated platform formed by the mitochondria-specific protein mS39. Mitoribosomal proteins of the large subunit mL40, mL48, and mL64 coordinate translocation of mt-tRNA. The comparison between those structures shows dynamic interactions between the mitoribosome and its ligands, suggesting a sequential mechanism of conformational changes.", "doi": "10.7554/elife.58362", "pmid": "32812867", "labels": {"Cryo-EM": "Service", "Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7438116"}, {"db": "pii", "key": "58362"}], "notes": [], "created": "2020-08-19T17:38:17.731Z", "modified": "2023-06-19T08:55:09.334Z"}, {"entity": "publication", "iuid": "8b85fb5237c649c98d5e35c07b496e3c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8b85fb5237c649c98d5e35c07b496e3c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8b85fb5237c649c98d5e35c07b496e3c"}}, "title": "Rapid size change associated with intra-island evolutionary radiation in extinct Caribbean \"island-shrews\".", "authors": [{"family": "Woods", "given": "Roseina", "initials": "R"}, {"family": "Turvey", "given": "Samuel T", "initials": "ST", "orcid": "0000-0002-3717-4800", "researcher": {"href": "https://publications.scilifelab.se/researcher/98f9849b335e4e74b810b08cabe6759a.json"}}, {"family": "Brace", "given": "Selina", "initials": "S"}, {"family": "McCabe", "given": "Christopher V", "initials": "CV"}, {"family": "Dal\u00e9n", "given": "Love", "initials": "L", "orcid": "0000-0001-8270-7613", "researcher": {"href": "https://publications.scilifelab.se/researcher/48ecf726779249ac9d12f4f7a1cc62bf.json"}}, {"family": "Rayfield", "given": "Emily J", "initials": "EJ"}, {"family": "Brown", "given": "Mark J F", "initials": "MJF"}, {"family": "Barnes", "given": "Ian", "initials": "I"}], "type": "journal article", "published": "2020-08-18", "journal": {"title": "BMC Evol. Biol.", "issn": "1471-2148", "volume": "20", "issue": "1", "pages": "106", "issn-l": "1471-2148"}, "abstract": "The Caribbean offers a unique opportunity to study evolutionary dynamics in insular mammals. However, the recent extinction of most Caribbean non-volant mammals has obstructed evolutionary studies, and poor DNA preservation associated with tropical environments means that very few ancient DNA sequences are available for extinct vertebrates known from the region's Holocene subfossil record. The endemic Caribbean eulipotyphlan family Nesophontidae (\"island-shrews\") became extinct ~ 500 years ago, and the taxonomic validity of many Nesophontes species and their wider evolutionary dynamics remain unclear. Here we use both morphometric and palaeogenomic methods to clarify the status and evolutionary history of Nesophontes species from Hispaniola, the second-largest Caribbean island.\n\nPrincipal component analysis of 65 Nesophontes mandibles from late Quaternary fossil sites across Hispaniola identified three non-overlapping morphometric clusters, providing statistical support for the existence of three size-differentiated Hispaniolan Nesophontes species. We were also able to extract and sequence ancient DNA from a ~ 750-year-old specimen of Nesophontes zamicrus, the smallest non-volant Caribbean mammal, including a whole-mitochondrial genome and partial nuclear genes. Nesophontes paramicrus (39-47 g) and N. zamicrus (~ 10 g) diverged recently during the Middle Pleistocene (mean estimated divergence = 0.699 Ma), comparable to the youngest species splits in Eulipotyphla and other mammal groups. Pairwise genetic distance values for N. paramicrus and N. zamicrus based on mitochondrial and nuclear genes are low, but fall within the range of comparative pairwise data for extant eulipotyphlan species-pairs.\n\nOur combined morphometric and palaeogenomic analyses provide evidence for multiple co-occurring species and rapid body size evolution in Hispaniolan Nesophontes, in contrast to patterns of genetic and morphometric differentiation seen in Hispaniola's extant non-volant land mammals. Different components of Hispaniola's mammal fauna have therefore exhibited drastically different rates of morphological evolution. Morphological evolution in Nesophontes is also rapid compared to patterns across the Eulipotyphla, and our study provides an important new example of rapid body size change in a small-bodied insular vertebrate lineage. The Caribbean was a hotspot for evolutionary diversification as well as preserving ancient biodiversity, and studying the surviving representatives of its mammal fauna is insufficient to reveal the evolutionary patterns and processes that generated regional diversity.", "doi": "10.1186/s12862-020-01668-7", "pmid": "32811443", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12862-020-01668-7"}, {"db": "pmc", "key": "PMC7437022"}], "notes": [], "created": "2020-12-07T16:29:53.095Z", "modified": "2021-11-10T12:48:12.533Z"}, {"entity": "publication", "iuid": "c5bf06f322094e4e9cd44ec502fe6de1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c5bf06f322094e4e9cd44ec502fe6de1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c5bf06f322094e4e9cd44ec502fe6de1"}}, "title": "High Cysteine Membrane Proteins (HCMPs) Are Up-Regulated During Giardia-Host Cell Interactions.", "authors": [{"family": "Peirasmaki", "given": "Dimitra", "initials": "D"}, {"family": "Ma'ayeh", "given": "Showgy Y", "initials": "SY"}, {"family": "Xu", "given": "Feifei", "initials": "F"}, {"family": "Ferella", "given": "Marcela", "initials": "M"}, {"family": "Campos", "given": "Sara", "initials": "S"}, {"family": "Liu", "given": "Jingyi", "initials": "J"}, {"family": "Sv\u00e4rd", "given": "Staffan G", "initials": "SG"}], "type": "journal article", "published": "2020-08-18", "journal": {"title": "Front Genet", "issn": "1664-8021", "volume": "11", "issue": null, "pages": "913", "issn-l": "1664-8021"}, "abstract": "Giardia intestinalis colonizes the upper small intestine of humans and animals, causing the diarrheal disease giardiasis. This unicellular eukaryotic parasite is not invasive but it attaches to the surface of small intestinal epithelial cells (IECs), disrupting the epithelial barrier. Here, we used an in vitro model of the parasite's interaction with host IECs (differentiated Caco-2 cells) and RNA sequencing (RNAseq) to identify differentially expressed genes (DEGs) in Giardia, which might relate to the establishment of infection and disease induction. Giardia trophozoites interacted with differentiated Caco-2 cells for 1.5, 3, and 4.5 h and at each time point, 61, 89, and 148 parasite genes were up-regulated more than twofold, whereas 209, 265, and 313 parasite genes were down-regulated more than twofold. The most abundant DEGs encode hypothetical proteins and members of the High Cysteine Membrane Protein (HCMP) family. Among the up-regulated genes we also observed proteins associated with proteolysis, cellular redox balance, as well as lipid and nucleic acid metabolic pathways. In contrast, genes encoding kinases, regulators of the cell cycle and arginine metabolism and cytoskeletal proteins were down-regulated. Immunofluorescence imaging of selected, up-regulated HCMPs, using C-terminal HA-tagging, showed localization to the plasma membrane and peripheral vesicles (PVs). The expression of the HCMPs was affected by histone acetylation and free iron-levels. In fact, the latter was shown to regulate the expression of many putative giardial virulence factors in subsequent RNAseq experiments. We suggest that the plasma membrane localized and differentially expressed HCMPs play important roles during Giardia-host cell interactions.", "doi": "10.3389/fgene.2020.00913", "pmid": "33014015", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7461913"}], "notes": [], "created": "2020-10-06T11:59:57.373Z", "modified": "2021-11-10T12:48:13.692Z"}, {"entity": "publication", "iuid": "ca23b1230056405c893bae33407679c4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ca23b1230056405c893bae33407679c4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ca23b1230056405c893bae33407679c4"}}, "title": "Designing custom CRISPR libraries for hypothesis-driven drug target discovery.", "authors": [{"family": "Iyer", "given": "Vaishnavi Srinivasan", "initials": "VS"}, {"family": "Jiang", "given": "Long", "initials": "L", "orcid": "0000-0002-8720-8992", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d46414099a14d3ba156b86e18ff9a97.json"}}, {"family": "Shen", "given": "Yunbing", "initials": "Y"}, {"family": "Boddul", "given": "Sanjaykumar V", "initials": "SV"}, {"family": "Panda", "given": "Sudeepta Kumar", "initials": "SK"}, {"family": "Kasza", "given": "Zsolt", "initials": "Z"}, {"family": "Schmierer", "given": "Bernhard", "initials": "B", "orcid": "0000-0002-9082-7022", "researcher": {"href": "https://publications.scilifelab.se/researcher/d3ee96f9eb454850be6db3318b28479f.json"}}, {"family": "Wermeling", "given": "Fredrik", "initials": "F", "orcid": "0000-0001-9633-677X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a34df8186ba24df3b14fe9743cf546b4.json"}}], "type": "journal article", "published": "2020-08-18", "journal": {"title": "Computational and Structural Biotechnology Journal", "issn": "2001-0370", "volume": "18", "issue": null, "pages": "2237-2246", "issn-l": "2001-0370"}, "abstract": "Over the last decade Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) has been developed into a potent molecular biology tool used to rapidly modify genes or their expression in a multitude of ways. In parallel, CRISPR-based screening approaches have been developed as powerful discovery platforms for dissecting the genetic basis of cellular behavior, as well as for drug target discovery. CRISPR screens can be designed in numerous ways. Here, we give a brief background to CRISPR screens and discuss the pros and cons of different design approaches, including unbiased genome-wide screens that target all known genes, as well as hypothesis-driven custom screens in which selected subsets of genes are targeted (Fig. 1). We provide several suggestions for how a custom screen can be designed, which could broadly serve as inspiration for any experiment that includes candidate gene selection. Finally, we discuss how results from CRISPR screens could be translated into drug development, as well as future trends we foresee in the rapidly evolving CRISPR screen field.", "doi": "10.1016/j.csbj.2020.08.009", "pmid": "32952937", "labels": {"CRISPR Functional Genomics": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S2001-0370(20)30362-7"}, {"db": "pmc", "key": "PMC7479249"}], "notes": [], "created": "2020-11-10T16:34:04.296Z", "modified": "2024-01-16T13:48:41.924Z"}, {"entity": "publication", "iuid": "e761b3a5d96f4efbba18f980378013bf", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e761b3a5d96f4efbba18f980378013bf.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e761b3a5d96f4efbba18f980378013bf"}}, "title": "Association of Established Blood Pressure Loci With 10-Year Change in Blood Pressure and Their Ability to Predict Incident Hypertension.", "authors": [{"family": "Poveda", "given": "Alaitz", "initials": "A", "orcid": "0000-0001-6349-3955", "researcher": {"href": "https://publications.scilifelab.se/researcher/791a243b5c494d1688d757a7096895ea.json"}}, {"family": "Atabaki-Pasdar", "given": "Naeimeh", "initials": "N"}, {"family": "Ahmad", "given": "Shafqat", "initials": "S"}, {"family": "Hallmans", "given": "G\u00f6ran", "initials": "G"}, {"family": "Renstr\u00f6m", "given": "Frida", "initials": "F"}, {"family": "Franks", "given": "Paul W", "initials": "PW"}], "type": "journal article", "published": "2020-08-18", "journal": {"title": "J Am Heart Assoc", "issn": "2047-9980", "volume": "9", "issue": "16", "pages": "e014513", "issn-l": "2047-9980"}, "abstract": "Background Genome-wide association studies have identified >1000 genetic variants cross-sectionally associated with blood pressure variation and prevalent hypertension. These discoveries might aid the early identification of subpopulations at risk of developing hypertension or provide targets for drug development, amongst other applications. The aim of the present study was to analyze the association of blood pressure-associated variants with long-term changes (10 years) in blood pressure and also to assess their ability to predict hypertension incidence compared with traditional risk variables in a Swedish population. Methods and Results We constructed 6 genetic risk scores (GRSs) by summing the dosage of the effect allele at each locus of genetic variants previously associated with blood pressure traits (systolic blood pressure GRS (GRSSBP): 554 variants; diastolic blood pressure GRS (GRSDBP): 481 variants; mean arterial pressure GRS (GRSMAP): 20 variants; pulse pressure GRS (GRSPP): 478 variants; hypertension GRS (GRSHTN): 22 variants; combined GRS (GRScomb): 1152 variants). Each GRS was longitudinally associated with its corresponding blood pressure trait, with estimated effects per GRS SD unit of 0.50 to 1.21 mm Hg for quantitative traits and odds ratios (ORs) of 1.10 to 1.35 for hypertension incidence traits. The GRScomb was also significantly associated with hypertension incidence defined according to European guidelines (OR, 1.22 per SD; 95% CI, 1.10\u20121.35) but not US guidelines (OR, 1.11 per SD; 95% CI, 0.99\u20121.25) while controlling for traditional risk factors. The addition of GRScomb to a model containing traditional risk factors only marginally improved discrimination (\u0394area under the ROC curve = 0.001-0.002). Conclusions GRSs based on discovered blood pressure-associated variants are associated with long-term changes in blood pressure traits and hypertension incidence, but the inclusion of genetic factors in a model composed of conventional hypertension risk factors did not yield a material increase in predictive ability.", "doi": "10.1161/JAHA.119.014513", "pmid": "32805198", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7660819"}], "notes": [], "created": "2020-08-19T11:12:18.535Z", "modified": "2021-11-10T12:48:16.010Z"}, {"entity": "publication", "iuid": "80af4f01148941ee84d283dbe27a5578", "links": {"self": {"href": "https://publications.scilifelab.se/publication/80af4f01148941ee84d283dbe27a5578.json"}, "display": {"href": "https://publications.scilifelab.se/publication/80af4f01148941ee84d283dbe27a5578"}}, "title": "Platelet-Specific PDGFB Ablation Impairs Tumor Vessel Integrity and Promotes Metastasis.", "authors": [{"family": "Zhang", "given": "Yanyu", "initials": "Y"}, {"family": "Cedervall", "given": "Jessica", "initials": "J"}, {"family": "Hamidi", "given": "Anahita", "initials": "A", "orcid": "0000-0002-5445-2446", "researcher": {"href": "https://publications.scilifelab.se/researcher/fb5b0682d0bc4c2aae58ee0b20329da8.json"}}, {"family": "Herre", "given": "Melanie", "initials": "M"}, {"family": "Viitaniemi", "given": "Kati", "initials": "K"}, {"family": "D'Amico", "given": "Gabriela", "initials": "G"}, {"family": "Miao", "given": "Zuoxiu", "initials": "Z"}, {"family": "Unnithan", "given": "Ragaseema Valsala Madhavan", "initials": "RVM", "orcid": "0000-0002-5915-1685", "researcher": {"href": "https://publications.scilifelab.se/researcher/64fc9f8e946e4e50bb181c5048e7f364.json"}}, {"family": "Vaccaro", "given": "Alessandra", "initials": "A"}, {"family": "van Hooren", "given": "Luuk", "initials": "L"}, {"family": "Georganaki", "given": "Maria", "initials": "M"}, {"family": "Thulin", "given": "\u00c5sa", "initials": "\u00c5"}, {"family": "Qiao", "given": "Qi", "initials": "Q"}, {"family": "Andrae", "given": "Johanna", "initials": "J"}, {"family": "Siegbahn", "given": "Agneta", "initials": "A"}, {"family": "Heldin", "given": "Carl-Henrik", "initials": "CH"}, {"family": "Alitalo", "given": "Kari", "initials": "K"}, {"family": "Betsholtz", "given": "Christer", "initials": "C"}, {"family": "Dimberg", "given": "Anna", "initials": "A"}, {"family": "Olsson", "given": "Anna-Karin", "initials": "AK"}], "type": "journal article", "published": "2020-08-15", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "volume": "80", "issue": "16", "pages": "3345-3358", "issn-l": "0008-5472"}, "abstract": "Platelet-derived growth factor B (PDGFB) plays a crucial role in recruitment of PDGF receptor \u03b2-positive pericytes to blood vessels. The endothelium is an essential source of PDGFB in this process. Platelets constitute a major reservoir of PDGFB and are continuously activated in the tumor microenvironment, exposing tumors to the plethora of growth factors contained in platelet granules. Here, we show that tumor vascular function, as well as pericyte coverage is significantly impaired in mice with conditional knockout of PDGFB in platelets. A lack of PDGFB in platelets led to enhanced hypoxia and epithelial-to-mesenchymal transition in the primary tumors, elevated levels of circulating tumor cells, and increased spontaneous metastasis to the liver or lungs in two mouse models. These findings establish a previously unknown role for platelet-derived PDGFB, whereby it promotes and maintains vascular integrity in the tumor microenvironment by contributing to the recruitment of pericytes. SIGNIFICANCE: Conditional knockout of PDGFB in platelets demonstrates its previously unknown role in the maintenance of tumor vascular integrity and host protection against metastasis.", "doi": "10.1158/0008-5472.CAN-19-3533", "pmid": "32586981", "labels": {"PLA and Single Cell Proteomics": "Service", "Affinity Proteomics Uppsala": "Service"}, "xrefs": [{"db": "pii", "key": "0008-5472.CAN-19-3533"}], "notes": [], "created": "2020-08-26T14:42:44.583Z", "modified": "2023-04-14T13:55:52.207Z"}, {"entity": "publication", "iuid": "911de50d46654337a749860d7a8635b1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/911de50d46654337a749860d7a8635b1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/911de50d46654337a749860d7a8635b1"}}, "title": "Crystal structures of human PAICS reveal substrate and product binding of an emerging cancer target.", "authors": [{"family": "\u0160kerlov\u00e1", "given": "Jana", "initials": "J", "orcid": "0000-0002-9579-4047", "researcher": {"href": "https://publications.scilifelab.se/researcher/cde5c1c6ccb94ca3be0b092771e67524.json"}}, {"family": "Unterlass", "given": "Judith", "initials": "J"}, {"family": "G\u00f6ttmann", "given": "Mona", "initials": "M"}, {"family": "Marttila", "given": "Petra", "initials": "P", "orcid": "0000-0002-0115-8067", "researcher": {"href": "https://publications.scilifelab.se/researcher/2e3e92bdf843456784f98d3b521d2ccd.json"}}, {"family": "Homan", "given": "Evert", "initials": "E"}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS", "orcid": "0000-0002-7550-1833", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd07c6c543544af1a904e039f73ba857.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications.scilifelab.se/researcher/d97eba9f5edf4d76a5259c4baa8366c5.json"}}], "type": "journal article", "published": "2020-08-14", "journal": {"title": "J. Biol. Chem.", "issn": "1083-351X", "volume": "295", "issue": "33", "pages": "11656-11668", "issn-l": "0021-9258"}, "abstract": "The bifunctional human enzyme phosphoribosylaminoimidazole carboxylase and phosphoribosylaminoimidazolesuccinocarboxamide synthetase (PAICS) catalyzes two essential steps in the de novo purine biosynthesis pathway. PAICS is overexpressed in many cancers and could be a promising target for the development of cancer therapeutics. Here, using gene knockdowns and clonogenic survival and cell viability assays, we demonstrate that PAICS is required for growth and survival of prostate cancer cells. PAICS catalyzes the carboxylation of aminoimidazole ribonucleotide (AIR) and the subsequent conversion of carboxyaminoimidazole ribonucleotide (CAIR) and l-aspartate to N-succinylcarboxamide-5-aminoimidazole ribonucleotide (SAICAR). Of note, we present the first structures of human octameric PAICS in complexes with native ligands. In particular, we report the structure of PAICS with CAIR bound in the active sites of both domains and SAICAR bound in one of the SAICAR synthetase domains. Moreover, we report the PAICS structure with SAICAR and an ATP analog occupying the SAICAR synthetase active site. These structures provide insight into substrate and product binding and the architecture of the active sites, disclosing important structural information for rational design of PAICS inhibitors as potential anticancer drugs.", "doi": "10.1074/jbc.RA120.013695", "pmid": "32571877", "labels": {"Protein Science Facility (PSF)": "Service"}, "xrefs": [{"db": "pii", "key": "S0021-9258(17)48465-1"}, {"db": "pmc", "key": "PMC7450103"}, {"db": "PDB", "key": "5clj"}, {"db": "PDB", "key": "2h31"}, {"db": "PDB", "key": "4ja0"}, {"db": "PDB", "key": "3rgg"}, {"db": "PDB", "key": "2nsl"}, {"db": "PDB", "key": "2gqs"}, {"db": "PDB", "key": "4fe2"}, {"db": "PDB", "key": "4o7w"}, {"db": "PDB", "key": "2z02"}, {"db": "PDB", "key": "2cnv"}, {"db": "PDB", "key": "2cnu"}, {"db": "PDB", "key": "1obd"}], "notes": [], "created": "2020-10-03T09:58:37.898Z", "modified": "2021-11-10T12:48:19.342Z"}, {"entity": "publication", "iuid": "ec6422dbc5dc4b039f6c638f56ddcca9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ec6422dbc5dc4b039f6c638f56ddcca9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ec6422dbc5dc4b039f6c638f56ddcca9"}}, "title": "Gsta4 controls apoptosis of differentiating adult oligodendrocytes during homeostasis and remyelination via the mitochondria-associated Fas-Casp8-Bid-axis.", "authors": [{"family": "Carlstr\u00f6m", "given": "Karl E", "initials": "KE"}, {"family": "Zhu", "given": "Keying", "initials": "K", "orcid": "0000-0001-7500-1532", "researcher": {"href": "https://publications.scilifelab.se/researcher/2b85d1ae8136464788be19d62a8863d7.json"}}, {"family": "Ewing", "given": "Ewoud", "initials": "E", "orcid": "0000-0001-8644-366X", "researcher": {"href": "https://publications.scilifelab.se/researcher/aea9350a4f864d8e8781ab111b4f9273.json"}}, {"family": "Krabbendam", "given": "Inge E", "initials": "IE"}, {"family": "Harris", "given": "Robert A", "initials": "RA", "orcid": "0000-0003-4990-509X", "researcher": {"href": "https://publications.scilifelab.se/researcher/1b0733d3c25145139f42cad897d6726b.json"}}, {"family": "Falc\u00e3o", "given": "Ana Mendanha", "initials": "AM"}, {"family": "Jagodic", "given": "Maja", "initials": "M"}, {"family": "Castelo-Branco", "given": "Gon\u00e7alo", "initials": "G", "orcid": "0000-0003-2247-9393", "researcher": {"href": "https://publications.scilifelab.se/researcher/10b1a8fb48114340b8e390ca1f9e3321.json"}}, {"family": "Piehl", "given": "Fredrik", "initials": "F", "orcid": "0000-0001-8329-5219", "researcher": {"href": "https://publications.scilifelab.se/researcher/ee04062fbee34836a4fa3f4d2e8076cd.json"}}], "type": "journal article", "published": "2020-08-13", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "11", "issue": "1", "pages": "4071", "issn-l": "2041-1723"}, "abstract": "Arrest of oligodendrocyte (OL) differentiation and remyelination following myelin damage in multiple sclerosis (MS) is associated with neurodegeneration and clinical worsening. We show that Glutathione S-transferase 4\u03b1 (Gsta4) is highly expressed during adult OL differentiation and that Gsta4 loss impairs differentiation into myelinating OLs in vitro. In addition, we identify Gsta4 as a target of both dimethyl fumarate, an existing MS therapy, and clemastine fumarate, a candidate remyelinating agent in MS. Overexpression of Gsta4 reduces expression of Fas and activity of the mitochondria-associated Casp8-Bid-axis in adult oligodendrocyte precursor cells, leading to improved OL survival during differentiation. The Gsta4 effect on apoptosis during adult OL differentiation was corroborated in vivo in both lysolecithin-induced demyelination and experimental autoimmune encephalomyelitis models, where Casp8 activity was reduced in Gsta4-overexpressing OLs. Our results identify Gsta4 as an intrinsic regulator of OL differentiation, survival and remyelination, as well as a potential target for future reparative MS therapies.", "doi": "10.1038/s41467-020-17871-5", "pmid": "32792491", "labels": {"NGI Stockholm (Genomics Applications)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-17871-5"}, {"db": "pmc", "key": "PMC7426940"}], "notes": [], "created": "2021-01-08T16:29:42.593Z", "modified": "2024-01-16T13:48:41.933Z"}, {"entity": "publication", "iuid": "60bb471961234831b238c518363d3d74", "links": {"self": {"href": "https://publications.scilifelab.se/publication/60bb471961234831b238c518363d3d74.json"}, "display": {"href": "https://publications.scilifelab.se/publication/60bb471961234831b238c518363d3d74"}}, "title": "Variations in Plasma Membrane Topography Can Explain Heterogenous Diffusion Coefficients Obtained by Fluorescence Correlation Spectroscopy.", "authors": [{"family": "Gesper", "given": "Astrid", "initials": "A"}, {"family": "Wennmalm", "given": "Stefan", "initials": "S"}, {"family": "Hagemann", "given": "Philipp", "initials": "P"}, {"family": "Eriksson", "given": "Sven-G\u00f6ran", "initials": "SG"}, {"family": "Happel", "given": "Patrick", "initials": "P"}, {"family": "Parmryd", "given": "Ingela", "initials": "I"}], "type": "journal article", "published": "2020-08-11", "journal": {"title": "Front Cell Dev Biol", "issn": "2296-634X", "issn-l": null, "volume": "8", "issue": null, "pages": "767"}, "abstract": "Fluorescence correlation spectroscopy (FCS) is frequently used to study diffusion in cell membranes, primarily the plasma membrane. The diffusion coefficients reported in the plasma membrane of the same cell type and even within single cells typically display a large spread. We have investigated whether this spread can be explained by variations in membrane topography throughout the cell surface, that changes the amount of membrane in the FCS focal volume at different locations. Using FCS, we found that diffusion of the membrane dye DiI in the apical plasma membrane was consistently faster above the nucleus than above the cytoplasm. Using live cell scanning ion conductance microscopy (SICM) to obtain a topography map of the cell surface, we demonstrate that cell surface roughness is unevenly distributed with the plasma membrane above the nucleus being the smoothest, suggesting that the difference in diffusion observed in FCS is related to membrane topography. FCS modeled on simulated diffusion in cell surfaces obtained by SICM was consistent with the FCS data from live cells and demonstrated that topography variations can cause the appearance of anomalous diffusion in FCS measurements. Furthermore, we found that variations in the amount of the membrane marker DiD, a proxy for the membrane, but not the transmembrane protein TCR\u03b6 or the lipid-anchored protein Lck, in the FCS focal volume were related to variations in diffusion times at different positions in the plasma membrane. This relationship was seen at different positions both at the apical cell and basal cell sides. We conclude that it is crucial to consider variations in topography in the interpretation of FCS results from membranes.", "doi": "10.3389/fcell.2020.00767", "pmid": "32903922", "labels": {"Integrated Microscopy Technologies Stockholm": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC7443568"}], "notes": "https://www.frontiersin.org/articles/10.3389/fcell.2020.00767/full", "created": "2020-09-16T08:57:25.007Z", "modified": "2021-11-10T12:48:21.716Z"}, {"entity": "publication", "iuid": "be2d410b6d474dcdb78678c145767abe", "links": {"self": {"href": "https://publications.scilifelab.se/publication/be2d410b6d474dcdb78678c145767abe.json"}, "display": {"href": "https://publications.scilifelab.se/publication/be2d410b6d474dcdb78678c145767abe"}}, "title": "Transcriptional mutagenesis dramatically alters genome-wide p53 transactivation landscape.", "authors": [{"family": "Liang", "given": "Shuo", "initials": "S"}, {"family": "Ezerskyte", "given": "Monika", "initials": "M"}, {"family": "Wang", "given": "Jingwen", "initials": "J"}, {"family": "Pelechano", "given": "Vicent", "initials": "V"}, {"family": "Dreij", "given": "Kristian", "initials": "K"}], "type": "journal article", "published": "2020-08-11", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "13513", "issn-l": "2045-2322"}, "abstract": "The transcriptional error rate can be significantly increased by the presence of DNA lesions that instruct mis-insertion during transcription; a process referred to as transcriptional mutagenesis (TM) that can result in altered protein function. Herein, we determined the effect of O6-methylguanine (O6-meG) on transcription and subsequent transactivation activity of p53 in human lung H1299 cells. Levels of TM and effects on transactivation were determined genome wide by RNA-seq. Results showed that 47% of all p53 transcripts contained an uridine misincorporation opposite the lesion at 6 h post transfection, which was decreased to 18% at 24 h. TM at these levels reduced DNA binding activity of p53 to 21% and 80% compared to wild type p53, respectively. Gene expression data were analysed to identify differentially expressed genes due to TM of p53. We show a temporal repression of transactivation of > 100 high confidence p53 target genes including regulators of the cell cycle, DNA damage response and apoptosis. In addition, TM repressed the transcriptional downregulation by p53 of several negative regulators of proliferation and differentiation. Our work demonstrates that TM, even when restricting its effect to an individual transcription factor, has the potential to alter gene expression programs and diversify cellular phenotypes.", "doi": "10.1038/s41598-020-70412-4", "pmid": "32782319", "labels": {"NGI Stockholm (Genomics Applications)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-70412-4"}, {"db": "pmc", "key": "PMC7419513"}], "notes": [], "created": "2021-01-08T16:29:43.891Z", "modified": "2021-11-10T12:48:22.899Z"}, {"entity": "publication", "iuid": "c1968e5cd89444e58da6e554cce5605f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c1968e5cd89444e58da6e554cce5605f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c1968e5cd89444e58da6e554cce5605f"}}, "title": "Regular use of depot medroxyprogesterone acetate causes thinning of the superficial lining and apical distribution of HIV target cells in the human ectocervix.", "authors": [{"family": "Edfeldt", "given": "Gabriella", "initials": "G"}, {"family": "Lajoie", "given": "Julie", "initials": "J"}, {"family": "R\u00f6hl", "given": "Maria", "initials": "M"}, {"family": "Oyugi", "given": "Julius", "initials": "J"}, {"family": "\u00c5hlberg", "given": "Alexandra", "initials": "A"}, {"family": "Khalilzadeh-Binicy", "given": "Behnaz", "initials": "B"}, {"family": "Bradley", "given": "Frideborg", "initials": "F"}, {"family": "Mack", "given": "Mathias", "initials": "M"}, {"family": "Kimani", "given": "Joshua", "initials": "J"}, {"family": "Omollo", "given": "Kenneth", "initials": "K"}, {"family": "W\u00e4hlby", "given": "Carolina", "initials": "C", "orcid": "0000-0002-4139-7003", "researcher": {"href": "https://publications.scilifelab.se/researcher/c50194fbc8524d95b7152663ccf17f29.json"}}, {"family": "Fowke", "given": "Keith R", "initials": "KR"}, {"family": "Broliden", "given": "Kristina", "initials": "K"}, {"family": "Tjernlund", "given": "Annelie", "initials": "A"}], "type": "journal article", "published": "2020-08-11", "journal": {"title": "J. Infect. Dis.", "issn": "1537-6613", "issn-l": "0022-1899", "volume": null, "issue": null, "pages": null}, "abstract": "The hormonal contraceptive depot medroxyprogesterone acetate (DMPA) may be associated with an increased risk of acquiring human immunodeficiency virus (HIV). We hypothesize that DMPA use influences the ectocervical tissue architecture and HIV target cell localization.\r\n\r\nQuantitative image analysis workflows were developed to assess ectocervical tissue samples collected from DMPA users and control subjects not using hormonal contraception.\r\n\r\nCompared to controls, the DMPA group exhibited a significantly thinner apical ectocervical epithelial layer and a higher proportion of CD4+CCR5+ cells with a more superficial location. This localization corresponded to an area with a non-intact E-cadherin net structure. CD4+Langerin+ cells were also more superficially located in the DMPA group, while fewer in number compared to the controls. Natural plasma progesterone levels did not correlate with any of these parameters, whereas estradiol levels were positively correlated with E-cadherin expression and a more basal location for HIV target cells of the control group.\r\n\r\nDMPA users have a less robust epithelial layer and a more apical distribution of HIV target cells in the human ectocervix, which could confer a higher risk of HIV infection. Our results highlight the importance of assessing intact genital tissue samples to gain insights into HIV susceptibility factors.", "doi": "10.1093/infdis/jiaa514", "pmid": "32780807", "labels": {"BioImage Informatics": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pii", "key": "5891260"}], "notes": [], "created": "2020-11-30T10:24:22.436Z", "modified": "2022-03-29T11:54:23.722Z"}, {"entity": "publication", "iuid": "d04f44cd62564eadad0ce47ce505ff71", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d04f44cd62564eadad0ce47ce505ff71.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d04f44cd62564eadad0ce47ce505ff71"}}, "title": "Association of Factor V Leiden With Subsequent Atherothrombotic Events: A GENIUS-CHD Study of Individual Participant Data.", "authors": [{"family": "Mahmoodi", "given": "Bakhtawar K", "initials": "BK"}, {"family": "Tragante", "given": "Vinicius", "initials": "V"}, {"family": "Kleber", "given": "Marcus E", "initials": "ME"}, {"family": "Holmes", "given": "Michael V", "initials": "MV"}, {"family": "Schmidt", "given": "Amand F", "initials": "AF"}, {"family": "McCubrey", "given": "Raymond O", "initials": "RO"}, {"family": "Howe", "given": "Laurence J", "initials": "LJ"}, {"family": "Direk", "given": "Kenan", "initials": "K"}, {"family": "Allayee", "given": "Hooman", "initials": "H"}, {"family": "Baranova", "given": "Ekaterina V", "initials": "EV"}, {"family": "Braund", "given": "Peter S", "initials": "PS"}, {"family": "Delgado", "given": "Graciela E", "initials": "GE"}, {"family": "Eriksson", "given": "Niclas", "initials": "N"}, {"family": "Gijsberts", "given": "Crystel M", "initials": "CM"}, {"family": "Gong", "given": "Yan", "initials": "Y"}, {"family": "Hartiala", "given": "Jaana", "initials": "J", "orcid": "0000-0003-4883-9318", "researcher": {"href": "https://publications.scilifelab.se/researcher/f39400df71774cf8ae408eccbe34d981.json"}}, {"family": "Heydarpour", "given": "Mahyar", "initials": "M"}, {"family": "Pasterkamp", "given": "Gerard", "initials": "G"}, {"family": "Kotti", "given": "Salma", "initials": "S"}, {"family": "Kuukasj\u00e4rvi", "given": "Pekka", "initials": "P"}, {"family": "Lenzini", "given": "Petra A", "initials": "PA"}, {"family": "Levin", "given": "Daniel", "initials": "D"}, {"family": "Lyytik\u00e4inen", "given": "Leo-Pekka", "initials": "LP"}, {"family": "Muehlschlegel", "given": "Jochen D", "initials": "JD", "orcid": "0000-0002-6209-7253", "researcher": {"href": "https://publications.scilifelab.se/researcher/3211e8bb09c64d748cb153c358831d82.json"}}, {"family": "Nelson", "given": "Christopher P", "initials": "CP"}, {"family": "Nikus", "given": "Kjell", "initials": "K", "orcid": "0000-0002-9345-9851", "researcher": {"href": "https://publications.scilifelab.se/researcher/99b4b0a2893c42efbc24bed6370451ba.json"}}, {"family": "Pilbrow", "given": "Anna P", "initials": "AP", "orcid": "0000-0003-1949-9449", "researcher": {"href": "https://publications.scilifelab.se/researcher/b86a1225a68e403e806a07b42e96c991.json"}}, {"family": "Wilson Tang", "given": "W H", "initials": "WH", "orcid": "0000-0002-8335-735X", "researcher": {"href": "https://publications.scilifelab.se/researcher/5aab6a5657004a79aeda81c22a077268.json"}}, {"family": "van der Laan", "given": "Sander W", "initials": "SW", "orcid": "0000-0001-6888-1404", "researcher": {"href": "https://publications.scilifelab.se/researcher/9bd54ab413974b9096ff3d924f8b8eb6.json"}}, {"family": "van Setten", "given": "Jessica", "initials": "J"}, {"family": "Vilmundarson", "given": "Ragnar O", "initials": "RO"}, {"family": "Deanfield", "given": "John", "initials": "J"}, {"family": "Deloukas", "given": "Panos", "initials": "P", "orcid": "0000-0001-9251-070X", "researcher": {"href": "https://publications.scilifelab.se/researcher/eb59dbd2f2204d41b801c41188611a9e.json"}}, {"family": "Dudbridge", "given": "Frank", "initials": "F"}, {"family": "James", "given": "Stefan", "initials": "S"}, {"family": "Mordi", "given": "Ify R", "initials": "IR", "orcid": "0000-0002-2686-729X", "researcher": {"href": "https://publications.scilifelab.se/researcher/1081c6ce996d4f7e944be05db1a3e7c0.json"}}, {"family": "Teren", "given": "Andrej", "initials": "A"}, {"family": "Bergmeijer", "given": "Thomas O", "initials": "TO"}, {"family": "Body", "given": "Simon C", "initials": "SC"}, {"family": "Bots", "given": "Michiel", "initials": "M"}, {"family": "Burkhardt", "given": "Ralph", "initials": "R"}, {"family": "Cooper-DeHoff", "given": "Rhonda M", "initials": "RM"}, {"family": "Cresci", "given": "Sharon", "initials": "S"}, {"family": "Danchin", "given": "Nicolas", "initials": "N", "orcid": "0000-0001-9263-5051", "researcher": {"href": "https://publications.scilifelab.se/researcher/4c86ecd847894f7cb79f1f625881d60b.json"}}, {"family": "Doughty", "given": "Robert N", "initials": "RN"}, {"family": "Grobbee", "given": "Diederick E", "initials": "DE"}, {"family": "Hagstr\u00f6m", "given": "Emil", "initials": "E"}, {"family": "Hazen", "given": "Stanley L", "initials": "SL", "orcid": "0000-0001-7124-6639", "researcher": {"href": "https://publications.scilifelab.se/researcher/abce9cd916c94667a73bc348ede57a01.json"}}, {"family": "Held", "given": "Claes", "initials": "C"}, {"family": "Hoefer", "given": "Imo E", "initials": "IE"}, {"family": "Hovingh", "given": "G Kees", "initials": "GK"}, {"family": "Johnson", "given": "Julie A", "initials": "JA"}, {"family": "Kaczor", "given": "Marcin P", "initials": "MP"}, {"family": "K\u00e4h\u00f6nen", "given": "Mika", "initials": "M"}, {"family": "Klungel", "given": "Olaf H", "initials": "OH"}, {"family": "Laurikka", "given": "Jari O", "initials": "JO"}, {"family": "Lehtim\u00e4ki", "given": "Terho", "initials": "T"}, {"family": "Maitland-van der Zee", "given": "Anke H", "initials": "AH"}, {"family": "McPherson", "given": "Ruth", "initials": "R", "orcid": "0000-0002-9087-6107", "researcher": {"href": "https://publications.scilifelab.se/researcher/a563e055adb14878a8af46f235944082.json"}}, {"family": "Palmer", "given": "Colin N", "initials": "CN", "orcid": "0000-0002-6415-6560", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a0f019dcb7a453a84480953a5514dd5.json"}}, {"family": "Kraaijeveld", "given": "Adriaan O", "initials": "AO"}, {"family": "Pepine", "given": "Carl J", "initials": "CJ", "orcid": "0000-0002-6011-681X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a3b76ccaa8a749bd83a0bc35a2d97557.json"}}, {"family": "Sanak", "given": "Marek", "initials": "M"}, {"family": "Sattar", "given": "Naveed", "initials": "N", "orcid": "0000-0002-1604-2593", "researcher": {"href": "https://publications.scilifelab.se/researcher/80fbc7cdcfc444acb066449f80f87181.json"}}, {"family": "Scholz", "given": "Markus", "initials": "M"}, {"family": "Simon", "given": "Tabassome", "initials": "T"}, {"family": "Spertus", "given": "John A", "initials": "JA"}, {"family": "Stewart", "given": "Alexandre F R", "initials": "AFR", "orcid": "0000-0003-2673-9164", "researcher": {"href": "https://publications.scilifelab.se/researcher/f6cd21cc0681418d845ab97d09f953c1.json"}}, {"family": "Szczeklik", "given": "Wojciech", "initials": "W"}, {"family": "Thiery", "given": "Joachim", "initials": "J"}, {"family": "Visseren", "given": "Frank L J", "initials": "FLJ"}, {"family": "Waltenberger", "given": "Johannes", "initials": "J", "orcid": "0000-0002-2417-9880", "researcher": {"href": "https://publications.scilifelab.se/researcher/a541817a1b1c49d79273fe61df23886e.json"}}, {"family": "Richards", "given": "A Mark", "initials": "AM"}, {"family": "Lang", "given": "Chim C", "initials": "CC"}, {"family": "Cameron", "given": "Vicky A", "initials": "VA"}, {"family": "\u00c5kerblom", "given": "Axel", "initials": "A"}, {"family": "Pare", "given": "Guillaume", "initials": "G", "orcid": "0000-0002-6795-4760", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e23d12d8f5340a79e86a293593c9598.json"}}, {"family": "M\u00e4rz", "given": "Winfried", "initials": "W"}, {"family": "Samani", "given": "Nilesh J", "initials": "NJ", "orcid": "0000-0002-3286-8133", "researcher": {"href": "https://publications.scilifelab.se/researcher/2227aaf274e8424f8408318f336f3bf1.json"}}, {"family": "Hingorani", "given": "Aroon D", "initials": "AD"}, {"family": "Ten Berg", "given": "Jurri\u00ebn M", "initials": "JM"}, {"family": "Wallentin", "given": "Lars", "initials": "L"}, {"family": "Asselbergs", "given": "Folkert W", "initials": "FW", "orcid": "0000-0002-1692-8669", "researcher": {"href": "https://publications.scilifelab.se/researcher/7037429ef1304bdaabd837d242b1e6f5.json"}}, {"family": "Patel", "given": "Riyaz S", "initials": "RS"}], "type": "journal article", "published": "2020-08-11", "journal": {"title": "Circulation", "issn": "1524-4539", "volume": "142", "issue": "6", "pages": "546-555", "issn-l": "0009-7322"}, "abstract": "Studies examining the role of factor V Leiden among patients at higher risk of atherothrombotic events, such as those with established coronary heart disease (CHD), are lacking. Given that coagulation is involved in the thrombus formation stage on atherosclerotic plaque rupture, we hypothesized that factor V Leiden may be a stronger risk factor for atherothrombotic events in patients with established CHD.\n\nWe performed an individual-level meta-analysis including 25 prospective studies (18 cohorts, 3 case-cohorts, 4 randomized trials) from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) consortium involving patients with established CHD at baseline. Participating studies genotyped factor V Leiden status and shared risk estimates for the outcomes of interest using a centrally developed statistical code with harmonized definitions across studies. Cox proportional hazards regression models were used to obtain age- and sex-adjusted estimates. The obtained estimates were pooled using fixed-effect meta-analysis. The primary outcome was composite of myocardial infarction and CHD death. Secondary outcomes included any stroke, ischemic stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality.\n\nThe studies included 69 681 individuals of whom 3190 (4.6%) were either heterozygous or homozygous (n=47) carriers of factor V Leiden. Median follow-up per study ranged from 1.0 to 10.6 years. A total of 20 studies with 61 147 participants and 6849 events contributed to analyses of the primary outcome. Factor V Leiden was not associated with the combined outcome of myocardial infarction and CHD death (hazard ratio, 1.03 [95% CI, 0.92-1.16]; I=28%; 2P-heterogeneity=0.12). Subgroup analysis according to baseline characteristics or strata of traditional cardiovascular risk factors did not show relevant differences. Similarly, risk estimates for the secondary outcomes including stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality were also close to identity.\n\nFactor V Leiden was not associated with increased risk of subsequent atherothrombotic events and mortality in high-risk participants with established and treated CHD. Routine assessment of factor V Leiden status is unlikely to improve atherothrombotic events risk stratification in this population.", "doi": "10.1161/CIRCULATIONAHA.119.045526", "pmid": "32654539", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7493828"}, {"db": "mid", "key": "NIHMS1610813"}], "notes": [], "created": "2020-08-04T14:50:04.900Z", "modified": "2021-11-10T12:49:19.053Z"}, {"entity": "publication", "iuid": "334ff8346e7c4ab08d762177f2e68739", "links": {"self": {"href": "https://publications.scilifelab.se/publication/334ff8346e7c4ab08d762177f2e68739.json"}, "display": {"href": "https://publications.scilifelab.se/publication/334ff8346e7c4ab08d762177f2e68739"}}, "title": "Mebendazole is unique among tubulin-active drugs in activating the MEK-ERK pathway.", "authors": [{"family": "Andersson", "given": "Claes R", "initials": "CR"}, {"family": "Selvin", "given": "Tove", "initials": "T"}, {"family": "Blom", "given": "Kristin", "initials": "K"}, {"family": "Rubin", "given": "Jenny", "initials": "J"}, {"family": "Berglund", "given": "Malin", "initials": "M"}, {"family": "Jarvius", "given": "Malin", "initials": "M"}, {"family": "Lenhammar", "given": "Lena", "initials": "L"}, {"family": "Parrow", "given": "Vendela", "initials": "V"}, {"family": "Loskog", "given": "Angelica", "initials": "A"}, {"family": "Frykn\u00e4s", "given": "M\u00e5rten", "initials": "M"}, {"family": "Nygren", "given": "Peter", "initials": "P"}, {"family": "Larsson", "given": "Rolf", "initials": "R"}], "type": "journal article", "published": "2020-08-04", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "13124", "issn-l": "2045-2322"}, "abstract": "We recently showed that the anti-helminthic compound mebendazole (MBZ) has immunomodulating activity in monocyte/macrophage models and induces ERK signalling. In the present study we investigated whether MBZ induced ERK activation is shared by other tubulin binding agents (TBAs) and if it is observable also in other human cell types. Curated gene signatures for a panel of TBAs in the LINCS Connectivity Map (CMap) database showed a unique strong negative correlation of MBZ with MEK/ERK inhibitors indicating ERK activation also in non-haematological cell lines. L1000 gene expression signatures for MBZ treated THP-1 monocytes also connected negatively to MEK inhibitors. MEK/ERK phosphoprotein activity testing of a number of TBAs showed that only MBZ increased the activity in both THP-1 monocytes and PMA differentiated macrophages. Distal effects on ERK phosphorylation of the substrate P90RSK and release of IL1B followed the same pattern. The effect of MBZ on MEK/ERK phosphorylation was inhibited by RAF/MEK/ERK inhibitors in THP-1 models, CD3/IL2 stimulated PBMCs and a MAPK reporter HEK-293 cell line. MBZ was also shown to increase ERK activity in CD4+ T-cells from lupus patients with known defective ERK signalling. Given these mechanistic features MBZ is suggested suitable for treatment of diseases characterized by defective ERK signalling, notably difficult to treat autoimmune diseases.", "doi": "10.1038/s41598-020-68986-0", "pmid": "32753665", "labels": {"Drug Discovery and Development": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-68986-0"}, {"db": "pmc", "key": "PMC7403428"}], "notes": [], "created": "2020-12-10T12:22:36.140Z", "modified": "2025-10-17T13:05:07.972Z"}, {"entity": "publication", "iuid": "3b44ed8187d241faaa178f175341b55a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3b44ed8187d241faaa178f175341b55a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3b44ed8187d241faaa178f175341b55a"}}, "title": "Lysophosphatidic Acid-Mediated GPR35 Signaling in CX3CR1+ Macrophages Regulates Intestinal Homeostasis.", "authors": [{"family": "Kaya", "given": "Berna", "initials": "B"}, {"family": "Do\u00f1as", "given": "Cristian", "initials": "C"}, {"family": "Wuggenig", "given": "Philipp", "initials": "P"}, {"family": "Diaz", "given": "Oscar E", "initials": "OE"}, {"family": "Morales", "given": "Rodrigo A", "initials": "RA"}, {"family": "Melhem", "given": "Hassan", "initials": "H"}, {"family": "Swiss IBD. Cohort Investigators", "given": "", "initials": ""}, {"family": "Hern\u00e1ndez", "given": "Pedro P", "initials": "PP"}, {"family": "Kaymak", "given": "Tanay", "initials": "T"}, {"family": "Das", "given": "Srustidhar", "initials": "S"}, {"family": "Hruz", "given": "Petr", "initials": "P"}, {"family": "Franc", "given": "Yannick", "initials": "Y"}, {"family": "Geier", "given": "Florian", "initials": "F"}, {"family": "Ayata", "given": "C Korcan", "initials": "CK"}, {"family": "Villablanca", "given": "Eduardo J", "initials": "EJ", "orcid": "0000-0001-9522-9729", "researcher": {"href": "https://publications.scilifelab.se/researcher/6c6a2dde2d8f40ef82dfba0cf1b52c0d.json"}}, {"family": "Niess", "given": "Jan Hendrik", "initials": "JH"}], "type": "journal article", "published": "2020-08-04", "journal": {"title": "Cell Rep", "issn": "2211-1247", "issn-l": null, "volume": "32", "issue": "5", "pages": "107979"}, "abstract": "Single-nucleotide polymorphisms in the gene encoding G protein-coupled receptor 35 (GPR35) are associated with increased risk of inflammatory bowel disease. However, the mechanisms by which GPR35 modulates intestinal immune homeostasis remain undefined. Here, integrating zebrafish and mouse experimental models, we demonstrate that intestinal Gpr35 expression is microbiota dependent and enhanced upon inflammation. Moreover, murine GPR35+ colonic macrophages are characterized by enhanced production of pro-inflammatory cytokines. We identify lysophosphatidic acid (LPA) as a potential endogenous ligand produced during intestinal inflammation, acting through GPR35 to induce tumor necrosis factor (Tnf) expression in macrophages. Mice lacking Gpr35 in CX3CR1+ macrophages aggravate colitis when exposed to dextran sodium sulfate, which is associated with decreased transcript levels of the corticosterone-generating gene Cyp11b1 and macrophage-derived Tnf. Administration of TNF in these mice restores Cyp11b1 expression and intestinal corticosterone production and ameliorates DSS-induced colitis. Our findings indicate that LPA signals through GPR35 in CX3CR1+ macrophages to maintain TNF-mediated intestinal homeostasis.", "doi": "10.1016/j.celrep.2020.107979", "pmid": "32755573", "labels": {"Genome Engineering Zebrafish": "Service"}, "xrefs": [{"db": "pii", "key": "S2211-1247(20)30964-5"}], "notes": [], "created": "2020-09-01T13:35:28.011Z", "modified": "2021-12-09T14:05:29.136Z"}, {"entity": "publication", "iuid": "abd99c9cbeb84108a4223a35edffd333", "links": {"self": {"href": "https://publications.scilifelab.se/publication/abd99c9cbeb84108a4223a35edffd333.json"}, "display": {"href": "https://publications.scilifelab.se/publication/abd99c9cbeb84108a4223a35edffd333"}}, "title": "Heterogeneous somatostatin-expressing neuron population in mouse ventral tegmental area.", "authors": [{"family": "Nagaeva", "given": "Elina", "initials": "E", "orcid": "0000-0003-2828-6234", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ace1b6f3c0b4330b06d0569990d2a1d.json"}}, {"family": "Zubarev", "given": "Ivan", "initials": "I", "orcid": "0000-0002-1620-8485", "researcher": {"href": "https://publications.scilifelab.se/researcher/c6f06f3181cf4942849e1066bb2d237e.json"}}, {"family": "Bengtsson Gonzales", "given": "Carolina", "initials": "C"}, {"family": "Forss", "given": "Mikko", "initials": "M"}, {"family": "Nikouei", "given": "Kasra", "initials": "K"}, {"family": "de Miguel", "given": "Elena", "initials": "E"}, {"family": "Elsil\u00e4", "given": "Lauri", "initials": "L", "orcid": "0000-0002-9744-4753", "researcher": {"href": "https://publications.scilifelab.se/researcher/6bc11f9ea8954725ae917ff90f17d581.json"}}, {"family": "Linden", "given": "Anni-Maija", "initials": "AM"}, {"family": "Hjerling-Leffler", "given": "Jens", "initials": "J"}, {"family": "Augustine", "given": "George J", "initials": "GJ", "orcid": "0000-0001-7408-7485", "researcher": {"href": "https://publications.scilifelab.se/researcher/a17c43aa8c2d43cd997256f56d479b36.json"}}, {"family": "Korpi", "given": "Esa R", "initials": "ER", "orcid": "0000-0003-0683-4009", "researcher": {"href": "https://publications.scilifelab.se/researcher/f84d676eeceb4b08853a3017458dc46c.json"}}], "type": "journal article", "published": "2020-08-04", "journal": {"title": "Elife", "issn": "2050-084X", "issn-l": "2050-084X", "volume": "9", "issue": null, "pages": null}, "abstract": "The cellular architecture of the ventral tegmental area (VTA), the main hub of the brain reward system, remains only partially characterized. To extend the characterization to inhibitory neurons, we have identified three distinct subtypes of somatostatin (Sst)-expressing neurons in the mouse VTA. These neurons differ in their electrophysiological and morphological properties, anatomical localization, as well as mRNA expression profiles. Importantly, similar to cortical Sst-containing interneurons, most VTA Sst neurons express GABAergic inhibitory markers, but some of them also express glutamatergic excitatory markers and a subpopulation even express dopaminergic markers. Furthermore, only some of the proposed marker genes for cortical Sst neurons were expressed in the VTA Sst neurons. Physiologically, one of the VTA Sst neuron subtypes locally inhibited neighboring dopamine neurons. Overall, our results demonstrate the remarkable complexity and heterogeneity of VTA Sst neurons and suggest that these cells are multifunctional players in the midbrain reward circuitry.", "doi": "10.7554/eLife.59328", "pmid": "32749220", "labels": {"Eukaryotic Single Cell Genomics (ESCG)": "Service"}, "xrefs": [{"db": "pii", "key": "59328"}, {"db": "pmc", "key": "PMC7440918"}, {"db": "GEO", "key": "10.1038/s41586-018-0654-5"}], "notes": [], "created": "2020-12-11T12:52:57.236Z", "modified": "2021-11-10T12:48:28.129Z"}, {"entity": "publication", "iuid": "81f8017172254c37a519f7c4ef21984f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/81f8017172254c37a519f7c4ef21984f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/81f8017172254c37a519f7c4ef21984f"}}, "title": "The Relation Between Position and Chemical Composition of Bis-Indole Substituents Determines Their Interactions with G-Quadruplex DNA.", "authors": [{"family": "Prasad", "given": "Bagineni", "initials": "B", "orcid": "0000-0002-8498-1250", "researcher": {"href": "https://publications.scilifelab.se/researcher/6eaf800ddfd04f5aaa7b29802fe433d2.json"}}, {"family": "Das", "given": "Rabindra Nath", "initials": "RN", "orcid": "0000-0001-6347-2169", "researcher": {"href": "https://publications.scilifelab.se/researcher/fec8d8bcbe8648258cfbab86693c77c6.json"}}, {"family": "Jamroskovic", "given": "Jan", "initials": "J", "orcid": "0000-0001-6871-7663", "researcher": {"href": "https://publications.scilifelab.se/researcher/154847e2f84f4336a07e219fac6db2f9.json"}}, {"family": "Kumar", "given": "Rajendra", "initials": "R", "orcid": "0000-0002-7268-9519", "researcher": {"href": "https://publications.scilifelab.se/researcher/4ba57d44c650444aa51a030541d3bba7.json"}}, {"family": "Hedenstr\u00f6m", "given": "Mattias", "initials": "M"}, {"family": "Sabouri", "given": "Nasim", "initials": "N", "orcid": "0000-0002-4541-7702", "researcher": {"href": "https://publications.scilifelab.se/researcher/4bdc688dc85a4932acfdfffad8bfc443.json"}}, {"family": "Chorell", "given": "Erik", "initials": "E", "orcid": "0000-0003-2523-1940", "researcher": {"href": "https://publications.scilifelab.se/researcher/ada783ae0a824621a3b8e1024aae13a4.json"}}], "type": "journal article", "published": "2020-08-03", "journal": {"title": "Chemistry", "issn": "1521-3765", "volume": "26", "issue": "43", "pages": "9561-9572", "issn-l": "0947-6539"}, "abstract": "G-quadruplex (G4) DNA structures are linked to fundamental biological processes and human diseases, which has triggered the development of compounds that affect these DNA structures. However, more knowledge is needed about how small molecules interact with G4 DNA structures. This study describes the development of a new class of bis-indoles (3,3-diindolyl-methyl derivatives) and detailed studies of how they interact with G4 DNA using orthogonal assays, biophysical techniques, and computational studies. This revealed compounds that strongly bind and stabilize G4 DNA structures, and detailed binding interactions which for example, show that charge variance can play a key role in G4 DNA binding. Furthermore, the structure-activity relationships generated opened the possibilities to replace or introduce new substituents on the core structure, which is of key importance to optimize compound properties or introduce probes to further expand the possibilities of these compounds as tailored research tools to study G4 biology.", "doi": "10.1002/chem.202000579", "pmid": "32187406", "labels": {"Swedish NMR Centre": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC7497243"}], "notes": [], "created": "2020-03-30T11:43:49.969Z", "modified": "2025-10-17T13:03:56.658Z"}, {"entity": "publication", "iuid": "4aa4c4111c7b4d808a3b8c8a091d78a1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4aa4c4111c7b4d808a3b8c8a091d78a1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4aa4c4111c7b4d808a3b8c8a091d78a1"}}, "title": "zOPT: an open source optical projection tomography system and methods for rapid 3D zebrafish imaging.", "authors": [{"family": "Zhang", "given": "Hanqing", "initials": "H"}, {"family": "Waldmann", "given": "Laura", "initials": "L"}, {"family": "Manuel", "given": "Remy", "initials": "R"}, {"family": "Boije", "given": "Henrik", "initials": "H"}, {"family": "Haitina", "given": "Tatjana", "initials": "T"}, {"family": "Allalou", "given": "Amin", "initials": "A", "orcid": "0000-0003-4028-8443", "researcher": {"href": "https://publications.scilifelab.se/researcher/98fffa8e99254fb597bf07dea61d8e37.json"}}], "type": "journal article", "published": "2020-08-01", "journal": {"title": "Biomed. Opt. Express", "issn": "2156-7085", "issn-l": "2156-7085", "volume": "11", "issue": "8", "pages": "4290-4305"}, "abstract": "Optical projection tomography (OPT) is a 3D imaging alternative to conventional microscopy which allows imaging of millimeter-sized object with isotropic micrometer resolution. The zebrafish is an established model organism and an important tool used in genetic and chemical screening. The size and optical transparency of the embryo and larva makes them well suited for imaging using OPT. Here, we present an open-source implementation of an OPT platform, built around a customized sample stage, 3D-printed parts and open source algorithms optimized for the system. We developed a versatile automated workflow including a two-step image processing approach for correcting the center of rotation and generating accurate 3D reconstructions. Our results demonstrate high-quality 3D reconstruction using synthetic data as well as real data of live and fixed zebrafish. The presented 3D-printable OPT platform represents a fully open design, low-cost and rapid loading and unloading of samples. Our system offers the opportunity for researchers with different backgrounds to setup and run OPT for large scale experiments, particularly in studies using zebrafish larvae as their key model organism.", "doi": "10.1364/BOE.393519", "pmid": "32923043", "labels": {"BioImage Informatics": "Technology development", "Genome Engineering Zebrafish": "Service", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Technology development"}, "xrefs": [{"db": "pii", "key": "393519"}, {"db": "pmc", "key": "PMC7449731"}], "notes": [], "created": "2020-11-30T10:20:38.973Z", "modified": "2024-01-16T13:48:41.943Z"}, {"entity": "publication", "iuid": "d95b080355954cdda0d7e730b122d9e2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d95b080355954cdda0d7e730b122d9e2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d95b080355954cdda0d7e730b122d9e2"}}, "title": "Optical coherence tomography for thyroid pathology: 3D analysis of tissue microstructure.", "authors": [{"family": "Emil Tampu", "given": "Iulian", "initials": "I", "orcid": "0000-0002-7582-1706", "researcher": {"href": "https://publications.scilifelab.se/researcher/3f3497ed6c634acca2acca14a37d098c.json"}}, {"family": "Maintz", "given": "Michaela", "initials": "M"}, {"family": "Koller", "given": "Daniela", "initials": "D"}, {"family": "Johansson", "given": "Kenth", "initials": "K"}, {"family": "Gimm", "given": "Oliver", "initials": "O"}, {"family": "Capitanio", "given": "Arrigo", "initials": "A"}, {"family": "Eklund", "given": "Anders", "initials": "A"}, {"family": "Haj-Hosseini", "given": "Neda", "initials": "N", "orcid": "0000-0002-0555-8877", "researcher": {"href": "https://publications.scilifelab.se/researcher/7c00390b63594e7ea150a3ec742a812c.json"}}], "type": "journal article", "published": "2020-08-01", "journal": {"title": "Biomed. Opt. Express", "issn": "2156-7085", "volume": "11", "issue": "8", "pages": "4130-4149", "issn-l": "2156-7085"}, "abstract": "To investigate the potential of optical coherence tomography (OCT) to distinguish between normal and pathologic thyroid tissue, 3D OCT images were acquired on ex vivo thyroid samples from adult subjects (n=22) diagnosed with a variety of pathologies. The follicular structure was analyzed in terms of count, size, density and sphericity. Results showed that OCT images highly agreed with the corresponding histopatology and the calculated parameters were representative of the follicular structure variation. The analysis of OCT volumes provides quantitative information that could make automatic classification possible. Thus, OCT can be beneficial for intraoperative surgical guidance or in the pathology assessment routine.", "doi": "10.1364/BOE.394296", "pmid": "32923033", "labels": {"AIDA Data Hub": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7449746"}, {"db": "pii", "key": "394296"}], "notes": [], "created": "2023-05-25T16:03:42.844Z", "modified": "2023-05-25T16:03:42.872Z"}, {"entity": "publication", "iuid": "1c72116bf22e498797792df3c564ce88", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1c72116bf22e498797792df3c564ce88.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1c72116bf22e498797792df3c564ce88"}}, "title": "Uncovering the hidden diversity of litter-decomposition mechanisms in mushroom-forming fungi.", "authors": [{"family": "Floudas", "given": "Dimitrios", "initials": "D", "orcid": "0000-0002-6119-2590", "researcher": {"href": "https://publications.scilifelab.se/researcher/d083c79383704b0f813c53f862e31ca2.json"}}, {"family": "Bentzer", "given": "Johan", "initials": "J"}, {"family": "Ahr\u00e9n", "given": "Dag", "initials": "D"}, {"family": "Johansson", "given": "Tomas", "initials": "T"}, {"family": "Persson", "given": "Per", "initials": "P", "orcid": "0000-0001-9172-3068", "researcher": {"href": "https://publications.scilifelab.se/researcher/edffc6f9df60444a9480380c68e7d202.json"}}, {"family": "Tunlid", "given": "Anders", "initials": "A"}], "type": "journal article", "published": "2020-08-00", "journal": {"volume": "14", "issn": "1751-7370", "issue": "8", "title": "ISME J", "pages": "2046-2059", "issn-l": "1751-7362"}, "abstract": "Litter decomposing Agaricales play key role in terrestrial carbon cycling, but little is known about their decomposition mechanisms. We assembled datasets of 42 gene families involved in plant-cell-wall decomposition from seven newly sequenced litter decomposers and 35 other Agaricomycotina members, mostly white-rot and brown-rot species. Using sequence similarity and phylogenetics, we split the families into phylogroups and compared their gene composition across nutritional strategies. Subsequently, we used Raman spectroscopy to examine the ability of litter decomposers, white-rot fungi, and brown-rot fungi to decompose crystalline cellulose. Both litter decomposers and white-rot fungi share the enzymatic cellulose decomposition, whereas brown-rot fungi possess a distinct mechanism that disrupts cellulose crystallinity. However, litter decomposers and white-rot fungi differ with respect to hemicellulose and lignin degradation phylogroups, suggesting adaptation of the former group to the litter environment. Litter decomposers show high phylogroup diversity, which is indicative of high functional versatility within the group, whereas a set of white-rot species shows adaptation to bulk-wood decomposition. In both groups, we detected species that have unique characteristics associated with hitherto unknown adaptations to diverse wood and litter substrates. Our results suggest that the terms white-rot fungi and litter decomposers mask a much larger functional diversity.", "doi": "10.1038/s41396-020-0667-6", "pmid": "32382073", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41396-020-0667-6"}, {"db": "pmc", "key": "PMC7368018"}, {"db": "Dryad", "key": "10.5061/dryad.pk0p2ngk1"}], "notes": [], "created": "2020-05-15T08:57:38.045Z", "modified": "2021-12-10T10:02:12.162Z"}, {"entity": "publication", "iuid": "de7a823b3408405686545e6e19ec27f0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/de7a823b3408405686545e6e19ec27f0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/de7a823b3408405686545e6e19ec27f0"}}, "title": "The influence of forest surroundings on the soil fungal community of black truffle (Tuber melanosporum) plantations", "authors": [{"family": "Oliach", "given": "Daniel", "initials": "D"}, {"family": "Colinas", "given": "Carlos", "initials": "C"}, {"family": "Casta\u00f1o", "given": "Carles", "initials": "C"}, {"family": "Fischer", "given": "Christine R", "initials": "CR"}, {"family": "Bola\u00f1o", "given": "Francesc", "initials": "F"}, {"family": "Bonet", "given": "Jos\u00e9 Antonio", "initials": "JA"}, {"family": "Oliva", "given": "Jon\u00e0s", "initials": "J"}], "type": "journal-article", "published": "2020-08-00", "journal": {"title": "Forest Ecology and Management", "issn": "0378-1127", "volume": "469", "issue": null, "pages": "118199", "issn-l": null}, "abstract": null, "doi": "10.1016/j.foreco.2020.118199", "pmid": null, "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service"}, "xrefs": [], "notes": [], "created": "2020-05-26T18:03:39.205Z", "modified": "2021-11-10T12:36:49.991Z"}, {"entity": "publication", "iuid": "e73200548370435db06387414d40b7e2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e73200548370435db06387414d40b7e2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e73200548370435db06387414d40b7e2"}}, "title": "The importance of the ZBED6-IGF2 axis for metabolic regulation in mouse myoblast cells.", "authors": [{"family": "Younis", "given": "Shady", "initials": "S"}, {"family": "Naboulsi", "given": "Rakan", "initials": "R"}, {"family": "Wang", "given": "Xuan", "initials": "X"}, {"family": "Cao", "given": "Xiaofang", "initials": "X"}, {"family": "Larsson", "given": "M\u00e5rten", "initials": "M"}, {"family": "Sargsyan", "given": "Ernest", "initials": "E"}, {"family": "Bergsten", "given": "Peter", "initials": "P"}, {"family": "Welsh", "given": "Nils", "initials": "N"}, {"family": "Andersson", "given": "Leif", "initials": "L"}], "type": "journal article", "published": "2020-08-00", "journal": {"title": "FASEB J.", "issn": "1530-6860", "issn-l": "0892-6638", "volume": "34", "issue": "8", "pages": "10250-10266"}, "abstract": "The transcription factor ZBED6 acts as a repressor of Igf2 and affects directly or indirectly the transcriptional regulation of thousands of genes. Here, we use gene editing in mouse C2C12 myoblasts and show that ZBED6 regulates Igf2 exclusively through its binding site 5'-GGCTCG-3' in intron 1 of Igf2. Deletion of this motif (Igf2\u0394GGCT ) or complete ablation of Zbed6 leads to ~20-fold upregulation of the IGF2 protein. Quantitative proteomics revealed an activation of Ras signaling pathway in both Zbed6-/- and Igf2\u0394GGCT myoblasts, and a significant enrichment of mitochondrial membrane proteins among proteins showing altered expression in Zbed6-/- myoblasts. Both Zbed6-/- and Igf2\u0394GGCT myoblasts showed a faster growth rate and developed myotube hypertrophy. These cells exhibited an increased O2 consumption rate, due to IGF2 upregulation. Transcriptome analysis revealed ~30% overlap between differentially expressed genes in Zbed6-/- and Igf2\u0394GGCT myotubes, with an enrichment of upregulated genes involved in muscle development. In contrast, ZBED6-overexpression in myoblasts led to cell apoptosis, cell cycle arrest, reduced mitochondrial activities, and ceased myoblast differentiation. The similarities in growth and differentiation phenotypes observed in Zbed6-/- and Igf2\u0394GGCT myoblasts demonstrates that ZBED6 affects mitochondrial activity and myogenesis largely through its regulation of IGF2 expression. This study adds new insights how the ZBED6-Igf2 axis affects muscle metabolism.", "doi": "10.1096/fj.201901321R", "pmid": "32557799", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [], "notes": [], "created": "2020-12-08T23:27:45.177Z", "modified": "2024-01-16T13:48:41.959Z"}, {"entity": "publication", "iuid": "ba8e61b15fdf4091b7ee12bca3608e26", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ba8e61b15fdf4091b7ee12bca3608e26.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ba8e61b15fdf4091b7ee12bca3608e26"}}, "title": "The compact genome of Giardia muris reveals important steps in the evolution of intestinal protozoan parasites.", "authors": [{"family": "Xu", "given": "Feifei", "initials": "F", "orcid": "0000-0003-1946-1520", "researcher": {"href": "https://publications.scilifelab.se/researcher/84c51ec60768479f851e29ebc804f547.json"}}, {"family": "Jim\u00e9nez-Gonz\u00e1lez", "given": "Alejandro", "initials": "A", "orcid": "0000-0003-3493-4154", "researcher": {"href": "https://publications.scilifelab.se/researcher/f9c6b93b731741018637733969c308a6.json"}}, {"family": "Einarsson", "given": "Elin", "initials": "E", "orcid": "0000-0002-1242-5263", "researcher": {"href": "https://publications.scilifelab.se/researcher/be89fa4c7f9d484c858a0bf385f06c61.json"}}, {"family": "\u00c1stvaldsson", "given": "\u00c1sgeir", "initials": "\u00c1", "orcid": "0000-0002-0320-6974", "researcher": {"href": "https://publications.scilifelab.se/researcher/2a3d973dc6d246b48426d2063eef8934.json"}}, {"family": "Peirasmaki", "given": "Dimitra", "initials": "D", "orcid": "0000-0001-5376-626X", "researcher": {"href": "https://publications.scilifelab.se/researcher/94231cbd0cab4644b42c3fab58cea9aa.json"}}, {"family": "Eckmann", "given": "Lars", "initials": "L"}, {"family": "Andersson", "given": "Jan O", "initials": "JO", "orcid": "0000-0002-3075-4896", "researcher": {"href": "https://publications.scilifelab.se/researcher/489ed7f61a7b49a3a7ebd9ee3c391f5b.json"}}, {"family": "Sv\u00e4rd", "given": "Staffan G", "initials": "SG", "orcid": "0000-0002-7392-1746", "researcher": {"href": "https://publications.scilifelab.se/researcher/b01942d70ef84a1db3aaccab65af9c57.json"}}, {"family": "Jerlstr\u00f6m-Hultqvist", "given": "Jon", "initials": "J", "orcid": "0000-0002-7992-7970", "researcher": {"href": "https://publications.scilifelab.se/researcher/622d380bca244d738f5551cbed742b3e.json"}}], "type": "journal article", "published": "2020-08-00", "journal": {"title": "Microb Genom", "issn": "2057-5858", "volume": "6", "issue": "8", "issn-l": null}, "abstract": "Diplomonad parasites of the genus Giardia have adapted to colonizing different hosts, most notably the intestinal tract of mammals. The human-pathogenic Giardia species, Giardia intestinalis, has been extensively studied at the genome and gene expression level, but no such information is available for other Giardia species. Comparative data would be particularly valuable for Giardia muris, which colonizes mice and is commonly used as a prototypic in vivo model for investigating host responses to intestinal parasitic infection. Here we report the draft-genome of G. muris. We discovered a highly streamlined genome, amongst the most densely encoded ever described for a nuclear eukaryotic genome. G. muris and G. intestinalis share many known or predicted virulence factors, including cysteine proteases and a large repertoire of cysteine-rich surface proteins involved in antigenic variation. Different to G. intestinalis, G. muris maintains tandem arrays of pseudogenized surface antigens at the telomeres, whereas intact surface antigens are present centrally in the chromosomes. The two classes of surface antigens engage in genetic exchange. Reconstruction of metabolic pathways from the G. muris genome suggest significant metabolic differences to G. intestinalis. Additionally, G. muris encodes proteins that might be used to modulate the prokaryotic microbiota. The responsible genes have been introduced in the Giardia genus via lateral gene transfer from prokaryotic sources. Our findings point to important evolutionary steps in the Giardia genus as it adapted to different hosts and it provides a powerful foundation for mechanistic exploration of host-pathogen interaction in the G. muris-mouse pathosystem.", "doi": "10.1099/mgen.0.000402", "pmid": "32618561", "labels": {"NGI Stockholm (Genomics Applications)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7641422"}], "notes": [], "created": "2021-01-08T16:29:45.383Z", "modified": "2021-11-10T12:48:32.906Z"}, {"entity": "publication", "iuid": "56bd5b3292d745ebbee0c2a369c5a13c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/56bd5b3292d745ebbee0c2a369c5a13c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/56bd5b3292d745ebbee0c2a369c5a13c"}}, "title": "The Neolithic Pitted Ware culture foragers were culturally but not genetically influenced by the Battle Axe culture herders.", "authors": [{"family": "Coutinho", "given": "Alexandra", "initials": "A"}, {"family": "G\u00fcnther", "given": "Torsten", "initials": "T"}, {"family": "Munters", "given": "Arielle R", "initials": "AR"}, {"family": "Svensson", "given": "Emma M", "initials": "EM"}, {"family": "G\u00f6therstr\u00f6m", "given": "Anders", "initials": "A", "orcid": "0000-0001-6307-8188", "researcher": {"href": "https://publications.scilifelab.se/researcher/2a1a0a680ab8456cbf5a941e9718fd5a.json"}}, {"family": "Stor\u00e5", "given": "Jan", "initials": "J"}, {"family": "Malmstr\u00f6m", "given": "Helena", "initials": "H"}, {"family": "Jakobsson", "given": "Mattias", "initials": "M", "orcid": "0000-0001-7840-7853", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a4abe0fcb20492d9ec849c9fbf58a71.json"}}], "type": "historical article", "published": "2020-08-00", "journal": {"title": "Am. J. Phys. Anthropol.", "issn": "1096-8644", "volume": "172", "issue": "4", "pages": "638-649", "issn-l": "0002-9483"}, "abstract": "In order to understand contacts between cultural spheres in the third millennium BC, we investigated the impact of a new herder culture, the Battle Axe culture, arriving to Scandinavia on the people of the sub-Neolithic hunter-gatherer Pitted Ware culture. By investigating the genetic make-up of Pitted Ware culture people from two types of burials (typical Pitted Ware culture burials and Battle Axe culture-influenced burials), we could determine the impact of migration and the impact of cultural influences.\n\nWe sequenced and analyzed the genomes of 25 individuals from typical Pitted Ware culture burials and from Pitted Ware culture burials with Battle Axe culture influences in order to determine if the different burial types were associated with different gene-pools.\n\nThe genomic data show that all individuals belonged to one genetic population-a population associated with the Pitted Ware culture-irrespective of the burial style.\n\nWe conclude that the Pitted Ware culture communities were not impacted by gene-flow, that is, via migration or exchange of mates. These different cultural expressions in the Pitted Ware culture burials are instead a consequence of cultural exchange.", "doi": "10.1002/ajpa.24079", "pmid": "32497286", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [], "notes": [], "created": "2020-12-08T23:25:31.764Z", "modified": "2024-01-16T13:48:41.973Z"}, {"entity": "publication", "iuid": "f633a18574f5419eb4f2597a6da53b23", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f633a18574f5419eb4f2597a6da53b23.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f633a18574f5419eb4f2597a6da53b23"}}, "title": "Technologies for assessing vaccine responses in the very young.", "authors": [{"family": "Brodin", "given": "Petter", "initials": "P", "orcid": "0000-0002-8103-0046", "researcher": {"href": "https://publications.scilifelab.se/researcher/40097353cdb24e52bf2330eb687042bf.json"}}], "type": "journal article", "published": "2020-08-00", "journal": {"title": "Current Opinion in Immunology", "issn": "1879-0372", "volume": "65", "issue": null, "pages": "28-31", "issn-l": "0952-7915"}, "abstract": "Many vaccines are administered to young children in order to prevent infectious diseases early in life. At the same time, most of these vaccines are not developed specifically with the immune system of young children in mind and our understanding of how newborn immune systems differ from adult counterparts is incomplete. The main reason for this lack of understanding stems from the ethical and logistical difficulties in obtaining samples from young children as well as the challenges associated with the small volume samples available. Here I review some recent developments made in this field and discuss their implications for studying vaccine responses in young children and developing better vaccines, tailored to this important population of susceptible individuals in the future.", "doi": "10.1016/j.coi.2020.03.011", "pmid": "32339894", "labels": {"Cellular Immunomonitoring": "Technology development"}, "xrefs": [{"db": "pii", "key": "S0952-7915(20)30034-0"}], "notes": [], "created": "2020-04-25T09:30:22.101Z", "modified": "2021-11-10T12:48:35.165Z"}, {"entity": "publication", "iuid": "f0b41ac9f87d4487a698a8e955193a8f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f0b41ac9f87d4487a698a8e955193a8f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f0b41ac9f87d4487a698a8e955193a8f"}}, "title": "SWEDEGENE-a Swedish nation-wide DNA sample collection for pharmacogenomic studies of serious adverse drug reactions.", "authors": [{"family": "Hallberg", "given": "P\u00e4r", "initials": "P"}, {"family": "Yue", "given": "Qun-Ying", "initials": "QY"}, {"family": "Eliasson", "given": "Erik", "initials": "E"}, {"family": "Melhus", "given": "H\u00e5kan", "initials": "H"}, {"family": "\u00c5s", "given": "Joel", "initials": "J"}, {"family": "Wadelius", "given": "Mia", "initials": "M", "orcid": "0000-0002-6368-2622", "researcher": {"href": "https://publications.scilifelab.se/researcher/ec07b9869a1f4b77b734c5dc567dc630.json"}}], "type": "journal article", "published": "2020-08-00", "journal": {"volume": "20", "issn": "1473-1150", "issue": "4", "title": "Pharmacogenomics J.", "pages": "579-585", "issn-l": "1470-269X"}, "abstract": "SWEDEGENE is a Swedish nation-wide sample collection established to facilitate studies of clinical and genetic risk factors for adverse drug reactions (ADRs). Most cases are recruited among patients reported to the ADR registry at the Swedish Medical Products Agency by health-care professionals. Clinical data are collected both from medical and laboratory records and through interviews using standardized questionnaires. Genome-wide scans and whole-genome sequencing are done, and association studies are conducted using mainly controls from the Swedish TwinGene biobank with data on diagnoses and prescribed drugs. SWEDEGENE was established in 2008 and currently contains DNA and information from about 2550 adults who have experienced specific ADRs, and from 580 drug exposed controls. Results from genome-wide association studies have now been published, and data from whole-genome sequencing are being analyzed. SWEDEGENE has the potential to offer a new means of developing individualized and safe drug therapy through patient pre-treatment screening.", "doi": "10.1038/s41397-020-0148-3", "pmid": "31949290", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41397-020-0148-3"}, {"db": "pmc", "key": "PMC7375949"}], "notes": [], "created": "2020-01-22T08:25:49.135Z", "modified": "2024-01-16T13:48:41.982Z"}, {"entity": "publication", "iuid": "9eef175ae5b148708247024fc8f8d2d9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9eef175ae5b148708247024fc8f8d2d9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9eef175ae5b148708247024fc8f8d2d9"}}, "title": "SLC12A2 mutations cause NKCC1 deficiency with encephalopathy and impaired secretory epithelia.", "authors": [{"family": "St\u00f6dberg", "given": "Tommy", "initials": "T"}, {"family": "Magnusson", "given": "M\u00e5ns", "initials": "M"}, {"family": "Lesko", "given": "Nicole", "initials": "N"}, {"family": "Wredenberg", "given": "Anna", "initials": "A"}, {"family": "Martin Munoz", "given": "Daniel", "initials": "D"}, {"family": "Stranneheim", "given": "Henrik", "initials": "H"}, {"family": "Wedell", "given": "Anna", "initials": "A"}], "type": "journal article", "published": "2020-08-00", "journal": {"title": "Neurol Genet", "issn": "2376-7839", "volume": "6", "issue": "4", "pages": "e478", "issn-l": "2376-7839"}, "abstract": "To describe the phenotype in 2 sisters with a rare constellation of neurologic symptoms and secretory impairments and to identify the etiology by the use of whole-genome sequencing (WGS).\n\nAfter an extensive workup failed to reveal the cause of disease, in a girl with a previously not reported phenotype, WGS of the proband, her diseased older sister, an older healthy brother, and their parents was performed, and potentially pathogenic variants were analyzed.\n\nThe proband and her older sister both presented with neonatal Staphylococcus aureus parotitis, apneas, disappearance of the Moro reflex, and hypotonia. The proband survived. Her brain MRI showed white matter and basal ganglia abnormalities, and CSF damage biomarkers were increased. At age 8 years, she exhibits a constellation of symptoms including severe neurodevelopmental disorder, hearing impairment, gastrointestinal problems, and a striking lack of tear fluid, saliva, and sweat. Her respiratory mucosa is dry with potentially life-threatening mucus plugging. Through WGS, 2 loss-of-function variants in SLC12A2 were identified that follow an autosomal recessive inheritance pattern.\n\nTaken together with a single previously reported case and the close resemblance to the phenotypes of corresponding mouse models, our study firmly establishes biallelic variants in SLC12A2 as causing human disease and adds data regarding the neurologic phenotype.", "doi": "10.1212/NXG.0000000000000478", "pmid": "32754646", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "NG2020013649"}, {"db": "pmc", "key": "PMC7357422"}], "notes": [], "created": "2020-08-17T09:40:26.375Z", "modified": "2021-11-10T12:48:36.347Z"}, {"entity": "publication", "iuid": "efc537477cec47219f48e554a101fc12", "links": {"self": {"href": "https://publications.scilifelab.se/publication/efc537477cec47219f48e554a101fc12.json"}, "display": {"href": "https://publications.scilifelab.se/publication/efc537477cec47219f48e554a101fc12"}}, "title": "Recent introgression between Taiga Bean Goose and Tundra Bean Goose results in a largely homogeneous landscape of genetic differentiation.", "authors": [{"family": "Ottenburghs", "given": "Jente", "initials": "J", "orcid": "0000-0002-0335-9655", "researcher": {"href": "https://publications.scilifelab.se/researcher/ba165a24313c45a2bb601a47bf851eef.json"}}, {"family": "Honka", "given": "Johanna", "initials": "J"}, {"family": "M\u00fcskens", "given": "Gerard J D M", "initials": "GJDM"}, {"family": "Ellegren", "given": "Hans", "initials": "H", "orcid": "0000-0002-5035-1736", "researcher": {"href": "https://publications.scilifelab.se/researcher/819e68cc7125446baec6165aabd2d19c.json"}}], "type": "journal article", "published": "2020-08-00", "journal": {"title": "Heredity (Edinb)", "issn": "1365-2540", "volume": "125", "issue": "1-2", "pages": "73-84", "issn-l": "0018-067X"}, "abstract": "Several studies have uncovered a highly heterogeneous landscape of genetic differentiation across the genomes of closely related species. Specifically, genetic differentiation is often concentrated in particular genomic regions (\"islands of differentiation\") that might contain barrier loci contributing to reproductive isolation, whereas the rest of the genome is homogenized by introgression. Alternatively, linked selection can produce differentiation islands in allopatry without introgression. We explored the influence of introgression on the landscape of genetic differentiation in two hybridizing goose taxa: the Taiga Bean Goose (Anser fabalis) and the Tundra Bean Goose (A. serrirostris). We re-sequenced the whole genomes of 18 individuals (9 of each taxon) and, using a combination of population genomic summary statistics and demographic modeling, we reconstructed the evolutionary history of these birds. Next, we quantified the impact of introgression on the build-up and maintenance of genetic differentiation. We found evidence for a scenario of allopatric divergence (about 2.5 million years ago) followed by recent secondary contact (about 60,000 years ago). Subsequent introgression events led to high levels of gene flow, mainly from the Tundra Bean Goose into the Taiga Bean Goose. This scenario resulted in a largely undifferentiated genomic landscape (genome-wide FST = 0.033) with a few notable differentiation peaks that were scattered across chromosomes. The summary statistics indicated that some peaks might contain barrier loci while others arose in allopatry through linked selection. Finally, based on the low genetic differentiation, considerable morphological variation and incomplete reproductive isolation, we argue that the Taiga and the Tundra Bean Goose should be treated as subspecies.", "doi": "10.1038/s41437-020-0322-z", "pmid": "32451423", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41437-020-0322-z"}, {"db": "pmc", "key": "PMC7413267"}], "notes": [], "created": "2020-11-16T10:27:10.732Z", "modified": "2024-01-16T13:48:41.989Z"}, {"entity": "publication", "iuid": "43ac5630ef6c48389d5164ecaf4a37f9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/43ac5630ef6c48389d5164ecaf4a37f9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/43ac5630ef6c48389d5164ecaf4a37f9"}}, "title": "Preclinical safety studies of human embryonic stem cell-derived retinal pigment epithelial cells for the treatment of age-related macular degeneration.", "authors": [{"family": "Petrus-Reurer", "given": "Sandra", "initials": "S", "orcid": "0000-0002-7051-1741", "researcher": {"href": "https://publications.scilifelab.se/researcher/716f74c81a3240e5b612dab55e997267.json"}}, {"family": "Kumar", "given": "Pankaj", "initials": "P", "orcid": "0000-0002-8411-1634", "researcher": {"href": "https://publications.scilifelab.se/researcher/5e9109710e2e45009c332e257c3c498a.json"}}, {"family": "Padrell S\u00e1nchez", "given": "Sara", "initials": "S"}, {"family": "Aronsson", "given": "Monica", "initials": "M"}, {"family": "Andr\u00e9", "given": "Helder", "initials": "H"}, {"family": "Bartuma", "given": "Hammurabi", "initials": "H"}, {"family": "Plaza Reyes", "given": "Alvaro", "initials": "A"}, {"family": "Nandrot", "given": "Emeline F", "initials": "EF"}, {"family": "Kvanta", "given": "Anders", "initials": "A"}, {"family": "Lanner", "given": "Fredrik", "initials": "F", "orcid": "0000-0002-2771-7445", "researcher": {"href": "https://publications.scilifelab.se/researcher/ba53ce48a35d413eb86cd104488ce669.json"}}], "type": "journal article", "published": "2020-08-00", "journal": {"title": "Stem Cells Transl Med", "issn": "2157-6580", "issn-l": "2157-6564", "volume": "9", "issue": "8", "pages": "936-953"}, "abstract": "As pluripotent stem cell (PSC)-based reparative cell therapies are reaching the bedside, there is a growing need for the standardization of studies concerning safety of the derived products. Clinical trials using these promising strategies are in development, and treatment for age-related macular degeneration is one of the first that has reached patients. We have previously established a xeno-free and defined differentiation protocol to generate functional human embryonic stem cells (hESCs)-derived retinal pigment epithelial (RPE) cells. In this study, we perform preclinical safety studies including karyotype and whole-genome sequencing (WGS) to assess genome stability, single-cell RNA sequencing to ensure cell purity, and biodistribution and tumorigenicity analysis to rule out potential migratory or tumorigenic properties of these cells. WGS analysis illustrates that existing germline variants load is higher than the introduced variants acquired through in vitro culture or differentiation, and enforces the importance to examine the genome integrity at a deeper level than just karyotype. Altogether, we provide a strategy for preclinical evaluation of PSC-based therapies and the data support safety of the hESC-RPE cells generated through our in vitro differentiation methodology.", "doi": "10.1002/sctm.19-0396", "pmid": "32319201", "labels": {"Eukaryotic Single Cell Genomics (ESCG)": "Service", "NGI Stockholm (Genomics Production)": "Service", "NGI Stockholm (Genomics Applications)": "Service", "National Genomics Infrastructure": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7381808"}], "notes": [], "created": "2020-10-06T11:06:47.295Z", "modified": "2024-01-16T13:48:42.005Z"}, {"entity": "publication", "iuid": "bfb15759c8644cef8d58bca5a0c0e8c7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bfb15759c8644cef8d58bca5a0c0e8c7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bfb15759c8644cef8d58bca5a0c0e8c7"}}, "title": "MrpH, a new class of metal-binding adhesin, requires zinc to mediate biofilm formation.", "authors": [{"family": "Jiang", "given": "Wangshu", "initials": "W", "orcid": "0000-0003-1570-1208", "researcher": {"href": "https://publications.scilifelab.se/researcher/9908e45f950149e2963961d88783dabb.json"}}, {"family": "Ubhayasekera", "given": "Wimal", "initials": "W", "orcid": "0000-0001-5223-2434", "researcher": {"href": "https://publications.scilifelab.se/researcher/a01d8f6c38d3494a972b80f588f51f51.json"}}, {"family": "Breed", "given": "Michael C", "initials": "MC"}, {"family": "Norsworthy", "given": "Allison N", "initials": "AN"}, {"family": "Serr", "given": "Nina", "initials": "N", "orcid": "0000-0003-1335-0790", "researcher": {"href": "https://publications.scilifelab.se/researcher/5468ea52baea4e33a0c64ce395093c2d.json"}}, {"family": "Mobley", "given": "Harry L T", "initials": "HLT", "orcid": "0000-0001-9195-7665", "researcher": {"href": "https://publications.scilifelab.se/researcher/4db7193117fd4f5aaa3e2685372f01e2.json"}}, {"family": "Pearson", "given": "Melanie M", "initials": "MM", "orcid": "0000-0003-4553-3276", "researcher": {"href": "https://publications.scilifelab.se/researcher/2c675562ba474fdb81810f9fec308fe6.json"}}, {"family": "Knight", "given": "Stefan D", "initials": "SD", "orcid": "0000-0002-7180-8758", "researcher": {"href": "https://publications.scilifelab.se/researcher/9e9971d1ebb542a8b54601675c3869f5.json"}}], "type": "journal article", "published": "2020-08-00", "journal": {"title": "PLoS Pathog.", "issn": "1553-7374", "volume": "16", "issue": "8", "pages": "e1008707", "issn-l": "1553-7366"}, "abstract": "Proteus mirabilis, a Gram-negative uropathogen, is a major causative agent in catheter-associated urinary tract infections (CAUTI). Mannose-resistant Proteus-like fimbriae (MR/P) are crucially important for P. mirabilis infectivity and are required for biofilm formation and auto-aggregation, as well as for bladder and kidney colonization. Here, the X-ray crystal structure of the MR/P tip adhesin, MrpH, is reported. The structure has a fold not previously described and contains a transition metal center with Zn2+ coordinated by three conserved histidine residues and a ligand. Using biofilm assays, chelation, metal complementation, and site-directed mutagenesis of the three histidines, we show that an intact metal binding site occupied by zinc is essential for MR/P fimbria-mediated biofilm formation, and furthermore, that P. mirabilis biofilm formation is reversible in a zinc-dependent manner. Zinc is also required for MR/P-dependent agglutination of erythrocytes, and mutation of the metal binding site renders P. mirabilis unfit in a mouse model of UTI. The studies presented here provide important clues as to the mechanism of MR/P-mediated biofilm formation and serve as a starting point for identifying the physiological MR/P fimbrial receptor.", "doi": "10.1371/journal.ppat.1008707", "pmid": "32780778", "labels": {"Protein Science Facility (PSF)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7444556"}, {"db": "pii", "key": "PPATHOGENS-D-20-00342"}], "notes": [], "created": "2024-04-03T13:40:54.913Z", "modified": "2024-04-03T13:40:56.097Z"}, {"entity": "publication", "iuid": "27367ef1b782401c9275a385c207b933", "links": {"self": {"href": "https://publications.scilifelab.se/publication/27367ef1b782401c9275a385c207b933.json"}, "display": {"href": "https://publications.scilifelab.se/publication/27367ef1b782401c9275a385c207b933"}}, "title": "Management of an outbreak of postpartum Streptococcus pyogenes emm75 infections.", "authors": [{"family": "Trell", "given": "K", "initials": "K"}, {"family": "J\u00f6rgensen", "given": "J", "initials": "J"}, {"family": "Rasmussen", "given": "M", "initials": "M"}, {"family": "Senneby", "given": "E", "initials": "E"}], "type": "journal article", "published": "2020-08-00", "journal": {"title": "J. Hosp. Infect.", "issn": "1532-2939", "volume": "105", "issue": "4", "pages": "752-756", "issn-l": "0195-6701"}, "abstract": "Streptococcus pyogenes is a well-known cause of postpartum infections and is causing significant morbidity and mortality.\n\nTo describe measures taken to control an outbreak of postpartum infections caused by S. pyogenes emm75 on a maternity ward.\n\nPatients presenting postpartum with signs and symptoms of infection were cultured for \u03b2-haemolytic streptococci with cervical swabs and blood cultures, and bacterial isolates were species-determined with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and emm-typed. Pharyngeal swabs were taken from healthcare workers (HCWs) at the ward. Bacterial isolates were subjected to whole-genome sequencing (WGS). The multi-locus sequence type and the number of single nucleotide polymorphisms (SNPs) compared to an index genome were determined.\n\nDuring a three-month period, six cases of postpartum infection with S. pyogenes emm75 were identified on the maternity ward. By comparing delivery dates with duty rotas, one HCW was identified as a possible source of infection in five cases. After repeated pharyngeal swabs from this individual, an S. pyogenes emm75 was isolated. The five isolates from patients epidemiologically linked to the HCW and the two isolates of the family members had an identical sequence type (ST49) and 0-2 SNPs difference compared to the HCW isolate, whereas the sixth patient had an unrelated isolate. Eradication antibiotic therapy with clindamycin and rifampicin was given to the carrier. All patients received intravenous antibiotic treatment and recovered.\n\nA three-month outbreak was stopped when a carrier was identified and treated. Source identification and WGS proved vital for outbreak control.", "doi": "10.1016/j.jhin.2020.05.040", "pmid": "32497649", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Service", "National Genomics Infrastructure": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S0195-6701(20)30280-2"}], "notes": [], "created": "2020-09-15T07:51:34.984Z", "modified": "2024-01-16T13:48:42.020Z"}, {"entity": "publication", "iuid": "0762dde157384547b4115c069024cfd4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0762dde157384547b4115c069024cfd4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0762dde157384547b4115c069024cfd4"}}, "title": "Leveraging a gain-of-function allele of Caenorhabditis elegans paqr-1 to elucidate membrane homeostasis by PAQR proteins.", "authors": [{"family": "Busayavalasa", "given": "Kiran", "initials": "K"}, {"family": "Ruiz", "given": "Mario", "initials": "M", "orcid": "0000-0002-7149-6600", "researcher": {"href": "https://publications.scilifelab.se/researcher/35ea5372ccf64bad864d90e4b3698a24.json"}}, {"family": "Devkota", "given": "Ranjan", "initials": "R"}, {"family": "St\u00e5hlman", "given": "Marcus", "initials": "M", "orcid": "0000-0002-4202-0339", "researcher": {"href": "https://publications.scilifelab.se/researcher/01a323cbf0a24269bd32bfc34539e021.json"}}, {"family": "Bodhicharla", "given": "Rakesh", "initials": "R", "orcid": "0000-0002-2344-6318", "researcher": {"href": "https://publications.scilifelab.se/researcher/576a63da68ef49b1a6ff2052398029c3.json"}}, {"family": "Svensk", "given": "Emma", "initials": "E"}, {"family": "Hermansson", "given": "Nils-Olov", "initials": "NO", "orcid": "0000-0003-0170-6649", "researcher": {"href": "https://publications.scilifelab.se/researcher/55f9c6644b354a4891f528786cf81628.json"}}, {"family": "Bor\u00e9n", "given": "Jan", "initials": "J", "orcid": "0000-0003-0786-8091", "researcher": {"href": "https://publications.scilifelab.se/researcher/1e85f6d287ce4c60a7b35b287efb4f79.json"}}, {"family": "Pilon", "given": "Marc", "initials": "M", "orcid": "0000-0003-3919-2882", "researcher": {"href": "https://publications.scilifelab.se/researcher/d45c4ecf9afe463c971af2de53a770a8.json"}}], "type": "journal article", "published": "2020-08-00", "journal": {"title": "PLoS Genet.", "issn": "1553-7404", "volume": "16", "issue": "8", "pages": "e1008975", "issn-l": "1553-7390"}, "abstract": "The C. elegans proteins PAQR-2 (a homolog of the human seven-transmembrane domain AdipoR1 and AdipoR2 proteins) and IGLR-2 (a homolog of the mammalian LRIG proteins characterized by a single transmembrane domain and the presence of immunoglobulin domains and leucine-rich repeats in their extracellular portion) form a complex that protects against plasma membrane rigidification by promoting the expression of fatty acid desaturases and the incorporation of polyunsaturated fatty acids into phospholipids, hence increasing membrane fluidity. In the present study, we leveraged a novel gain-of-function allele of PAQR-1, a PAQR-2 paralog, to carry out structure-function studies. We found that the transmembrane domains of PAQR-2 are responsible for its functional requirement for IGLR-2, that PAQR-1 does not require IGLR-2 but acts via the same pathway as PAQR-2, and that the divergent N-terminal cytoplasmic domains of the PAQR-1 and PAQR-2 proteins serve a regulatory function and may regulate access to the catalytic site of these proteins. We also show that overexpression of human AdipoR1 or AdipoR2 alone is sufficient to confer increased palmitic acid resistance in HEK293 cells, and thus act in a manner analogous to the PAQR-1 gain-of-function allele.", "doi": "10.1371/journal.pgen.1008975", "pmid": "32750056", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7428288"}, {"db": "pii", "key": "PGENETICS-D-20-00388"}], "notes": [], "created": "2023-02-16T08:05:11.834Z", "modified": "2023-02-16T08:05:11.984Z"}, {"entity": "publication", "iuid": "aaf4daf85306445fb1289969ce10aa94", "links": {"self": {"href": "https://publications.scilifelab.se/publication/aaf4daf85306445fb1289969ce10aa94.json"}, "display": {"href": "https://publications.scilifelab.se/publication/aaf4daf85306445fb1289969ce10aa94"}}, "title": "Label\u2010free laser scanning microscopy targeting sentinel lymph node diagnostics: A feasibility study ex vivo", "authors": [{"family": "Kantere", "given": "Despoina", "initials": "D", "orcid": "0000-0001-9133-8581", "researcher": {"href": "https://publications.scilifelab.se/researcher/caafe30bd22040cf8a7043f692366fe3.json"}}, {"family": "Siarov", "given": "Jan", "initials": "J"}, {"family": "De Lara", "given": "Shahin", "initials": "S"}, {"family": "Parhizkar", "given": "Samad", "initials": "S"}, {"family": "Olofsson Bagge", "given": "Roger", "initials": "R"}, {"family": "Wennberg Lark\u00f6", "given": "Ann\u2010Marie", "initials": "A"}, {"family": "Ericson", "given": "Marica B", "initials": "MB"}], "type": "journal-article", "published": "2020-08-00", "journal": {"title": "Translational Biophotonics", "issn": "2627-1850", "volume": "2", "issue": "3", "issn-l": null}, "abstract": null, "doi": "10.1002/tbio.202000002", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2023-02-16T08:07:51.640Z", "modified": "2023-06-19T13:38:39.647Z"}, {"entity": "publication", "iuid": "3eb0ebe5e75646b48dd8e63889251ad4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3eb0ebe5e75646b48dd8e63889251ad4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3eb0ebe5e75646b48dd8e63889251ad4"}}, "title": "Joint impact of common risk factors on incident dementia: A cohort study of the Swedish Twin Registry.", "authors": [{"family": "Tomata", "given": "Y", "initials": "Y", "orcid": "0000-0003-4189-5245", "researcher": {"href": "https://publications.scilifelab.se/researcher/4f84f8bceff94af780a4a3bd8a4f09db.json"}}, {"family": "Li", "given": "X", "initials": "X", "orcid": "0000-0003-1922-7152", "researcher": {"href": "https://publications.scilifelab.se/researcher/862fd8b41938458f9105c5bb73c35294.json"}}, {"family": "Karlsson", "given": "I K", "initials": "IK"}, {"family": "Mosing", "given": "M A", "initials": "MA"}, {"family": "Pedersen", "given": "N L", "initials": "NL"}, {"family": "H\u00e4gg", "given": "S", "initials": "S"}], "type": "journal article", "published": "2020-08-00", "journal": {"volume": "288", "issn": "1365-2796", "issue": "2", "title": "J. Intern. Med.", "pages": "234-247", "issn-l": "0954-6820"}, "abstract": "As common risk factors of dementia, nine factors (low education, hearing loss, obesity, hypertension, smoking, depression, physical inactivity, diabetes and social isolation) were proposed. However, the joint impact of these factors on incident dementia is still uncertain; hence, we aimed to examine this impact.\n\nWe conducted a cohort study of 9017 cognitively intact individuals aged \u2265 65 years in the Swedish Twin Registry. The main exposure was the total number of reported risk factors (ranging from 0 to 9). Data on dementia diagnoses were based on clinical workup and national health registers. After estimating the adjusted hazard ratios of incident dementia, the population attributable fraction (PAF) was calculated. We then conducted additional analyses, including APOE \u03b54 status in a genotyped subsample (n = 2810) to check the relative impact of the main exposure and discordant twin pair (n = 1158) analysis to consider confounding by familial effects (shared genetic or familial environmental factors).\n\nThe number of dementia cases was 1950 (21.6%). A dose-response relationship between the number of risk factors and incident dementia was observed; hazard ratio (95% confidence interval) per one-unit increment in number of risk factors was 1.07 (1.03 to 1.11). The PAF for the combination of the nine risk factors was 10.4%. The PAF of all nine risk factors was smaller than that of APOE \u03b54 genotype (20.8%) in the subsample. Discordant pair analysis suggested that the observed association was not likely explained by familial effects.\n\nThe nine risk factors may have considerable impact as modifiable factors on incident dementia.", "doi": "10.1111/joim.13071", "pmid": "32363599", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [], "notes": [], "created": "2020-05-06T12:23:57.088Z", "modified": "2024-01-16T13:48:42.033Z"}, {"entity": "publication", "iuid": "77767504e98e44099323eb90a6f4d2c0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/77767504e98e44099323eb90a6f4d2c0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/77767504e98e44099323eb90a6f4d2c0"}}, "title": "Higher host plant specialization of root-associated endophytes than mycorrhizal fungi along an arctic elevational gradient.", "authors": [{"family": "Abrego", "given": "Nerea", "initials": "N", "orcid": "0000-0001-6347-6127", "researcher": {"href": "https://publications.scilifelab.se/researcher/547484556cdb43088e953f78e97f416e.json"}}, {"family": "Huotari", "given": "Tea", "initials": "T"}, {"family": "Tack", "given": "Ayco J M", "initials": "AJM", "orcid": "0000-0002-3550-1070", "researcher": {"href": "https://publications.scilifelab.se/researcher/7f9cf8fde705481281edab32bc9156e5.json"}}, {"family": "Lindahl", "given": "Bj\u00f6rn D", "initials": "BD", "orcid": "0000-0002-3384-4547", "researcher": {"href": "https://publications.scilifelab.se/researcher/b7a40688d33545a19c3c666940bda255.json"}}, {"family": "Tikhonov", "given": "Gleb", "initials": "G", "orcid": "0000-0003-3040-0307", "researcher": {"href": "https://publications.scilifelab.se/researcher/83ce2dc9d0304b0bb08de20ab8354446.json"}}, {"family": "Somervuo", "given": "Panu", "initials": "P", "orcid": "0000-0003-3121-4047", "researcher": {"href": "https://publications.scilifelab.se/researcher/bc4e5cf7203b4a2084034b7569dcd02c.json"}}, {"family": "Martin Schmidt", "given": "Niels", "initials": "N", "orcid": "0000-0002-4166-6218", "researcher": {"href": "https://publications.scilifelab.se/researcher/0248915d131f49869c9c34312664b57a.json"}}, {"family": "Ovaskainen", "given": "Otso", "initials": "O", "orcid": "0000-0001-9750-4421", "researcher": {"href": "https://publications.scilifelab.se/researcher/c754e5e5dc4244908a350074724a0418.json"}}, {"family": "Roslin", "given": "Tomas", "initials": "T", "orcid": "0000-0002-2957-4791", "researcher": {"href": "https://publications.scilifelab.se/researcher/04d92328b67e47ab82257567c07cf12f.json"}}], "type": "journal article", "published": "2020-08-00", "journal": {"title": "Ecol Evol", "issn": "2045-7758", "volume": "10", "issue": "16", "pages": "8989-9002", "issn-l": "2045-7758"}, "abstract": "How community-level specialization differs among groups of organisms, and changes along environmental gradients, is fundamental to understanding the mechanisms influencing ecological communities. In this paper, we investigate the specialization of root-associated fungi for plant species, asking whether the level of specialization varies with elevation. For this, we applied DNA barcoding based on the ITS region to root samples of five plant species equivalently sampled along an elevational gradient at a high arctic site. To assess whether the level of specialization changed with elevation and whether the observed patterns varied between mycorrhizal and endophytic fungi, we applied a joint species distribution modeling approach. Our results show that host plant specialization is not environmentally constrained in arctic root-associated fungal communities, since there was no evidence for changing specialization with elevation, even if the composition of root-associated fungal communities changed substantially. However, the level of specialization for particular plant species differed among fungal groups, root-associated endophytic fungal communities being highly specialized on particular host species, and mycorrhizal fungi showing almost no signs of specialization. Our results suggest that plant identity affects associated mycorrhizal and endophytic fungi differently, highlighting the need of considering both endophytic and mycorrhizal fungi when studying specialization in root-associated fungal communities.", "doi": "10.1002/ece3.6604", "pmid": "32884673", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Service", "National Genomics Infrastructure": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "ECE36604"}, {"db": "pmc", "key": "PMC7452766"}, {"db": "Dryad", "key": "10.5061/dryad.9dr6j0c"}], "notes": [], "created": "2020-09-15T06:17:19.364Z", "modified": "2024-01-16T13:48:42.043Z"}, {"entity": "publication", "iuid": "d01b44f867874897b9608bdee29225d5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d01b44f867874897b9608bdee29225d5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d01b44f867874897b9608bdee29225d5"}}, "title": "Evolutionary genetics of canine respiratory coronavirus and recent introduction into Swedish dogs.", "authors": [{"family": "Wille", "given": "Michelle", "initials": "M", "orcid": "0000-0002-5629-0196", "researcher": {"href": "https://publications.scilifelab.se/researcher/7be5504aedf3486295432bdc41ee654f.json"}}, {"family": "Wensman", "given": "Jonas Johansson", "initials": "JJ"}, {"family": "Larsson", "given": "Simon", "initials": "S"}, {"family": "van Damme", "given": "Renaud", "initials": "R"}, {"family": "Theelke", "given": "Anna-Karin", "initials": "AK"}, {"family": "Hayer", "given": "Juliette", "initials": "J"}, {"family": "Malmberg", "given": "Maja", "initials": "M", "orcid": "0000-0002-4506-0408", "researcher": {"href": "https://publications.scilifelab.se/researcher/e3d76ad702314dc5aa6dc3bf9a1918f8.json"}}], "type": "journal article", "published": "2020-08-00", "journal": {"title": "Infection, Genetics and Evolution", "issn": "1567-7257", "volume": "82", "issue": null, "pages": "104290", "issn-l": "1567-1348"}, "abstract": "Canine respiratory coronavirus (CRCoV) has been identified as a causative agent of canine infectious respiratory disease, an upper respiratory infection affecting dogs. The epidemiology is currently opaque, with an unclear understanding of global prevalence, pathology, and genetic characteristics. In this study, Swedish privately-owned dogs with characteristic signs of canine infectious respiratory disease (n = 88) were screened for CRCoV and 13 positive samples (14.7%, 8.4-23.7% [95% confidence interval (CI)]) were further sequenced. Sequenced Swedish CRCoV isolates were highly similar despite being detected in dogs living in geographically distant locations and sampled across 3 years (2013-2015). This is due to a single introduction into Swedish dogs in approximately 2010, as inferred by time structured phylogeny. Unlike other CRCoVs, there was no evidence of recombination in Swedish CRCoV viruses, further supporting a single introduction. Finally, there were low levels of polymorphisms, in the spike genes. Overall, we demonstrate that there is little diversity of CRCoV which is endemic in Swedish dogs.", "doi": "10.1016/j.meegid.2020.104290", "pmid": "32205264", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S1567-1348(20)30121-0"}, {"db": "pmc", "key": "PMC7102562"}], "notes": [], "created": "2020-03-24T07:55:16.030Z", "modified": "2024-01-16T13:48:42.051Z"}, {"entity": "publication", "iuid": "2ec4096268f347c79eedea7bb77234a9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2ec4096268f347c79eedea7bb77234a9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2ec4096268f347c79eedea7bb77234a9"}}, "title": "Determinants of genetic variation across eco-evolutionary scales in pinnipeds.", "authors": [{"family": "Peart", "given": "Claire R", "initials": "CR", "orcid": "0000-0002-0433-0299", "researcher": {"href": "https://publications.scilifelab.se/researcher/39ca9ce827fb435195a0d5bee245ba6a.json"}}, {"family": "Tusso", "given": "Sergio", "initials": "S", "orcid": "0000-0002-0612-9230", "researcher": {"href": "https://publications.scilifelab.se/researcher/027fc05d9bd843afaa82aeecce0747e8.json"}}, {"family": "Pophaly", "given": "Saurabh D", "initials": "SD"}, {"family": "Botero-Castro", "given": "Fidel", "initials": "F", "orcid": "0000-0002-5062-8272", "researcher": {"href": "https://publications.scilifelab.se/researcher/7ef9abb38c5d4c259d64e6f59ee7440c.json"}}, {"family": "Wu", "given": "Chi-Chih", "initials": "CC"}, {"family": "Aurioles-Gamboa", "given": "David", "initials": "D"}, {"family": "Baird", "given": "Amy B", "initials": "AB"}, {"family": "Bickham", "given": "John W", "initials": "JW", "orcid": "0000-0001-9624-7806", "researcher": {"href": "https://publications.scilifelab.se/researcher/5b8ef9c3991c4da38ad3010bb30977be.json"}}, {"family": "Forcada", "given": "Jaume", "initials": "J", "orcid": "0000-0002-2115-0150", "researcher": {"href": "https://publications.scilifelab.se/researcher/c9fddd47f5b64f779913b9fd631edb2e.json"}}, {"family": "Galimberti", "given": "Filippo", "initials": "F", "orcid": "0000-0001-5537-6409", "researcher": {"href": "https://publications.scilifelab.se/researcher/9d82a8f8835145619fbac351091bfbec.json"}}, {"family": "Gemmell", "given": "Neil J", "initials": "NJ", "orcid": "0000-0003-0671-3637", "researcher": {"href": "https://publications.scilifelab.se/researcher/9ca2b0a676d84b878b3f9faa8748e148.json"}}, {"family": "Hoffman", "given": "Joseph I", "initials": "JI", "orcid": "0000-0001-5895-8949", "researcher": {"href": "https://publications.scilifelab.se/researcher/5455275134754093b050bee85b8f88c5.json"}}, {"family": "Kovacs", "given": "Kit M", "initials": "KM"}, {"family": "Kunnasranta", "given": "Mervi", "initials": "M"}, {"family": "Lydersen", "given": "Christian", "initials": "C"}, {"family": "Nyman", "given": "Tommi", "initials": "T"}, {"family": "de Oliveira", "given": "Larissa Rosa", "initials": "LR"}, {"family": "Orr", "given": "Anthony J", "initials": "AJ"}, {"family": "Sanvito", "given": "Simona", "initials": "S", "orcid": "0000-0003-1427-6414", "researcher": {"href": "https://publications.scilifelab.se/researcher/1f65216b298b4575adb46bfeea38d8d3.json"}}, {"family": "Valtonen", "given": "Mia", "initials": "M", "orcid": "0000-0003-2034-2019", "researcher": {"href": "https://publications.scilifelab.se/researcher/601fe0084ca1460486e607e509f46c3a.json"}}, {"family": "Shafer", "given": "Aaron B A", "initials": "ABA", "orcid": "0000-0001-7652-225X", "researcher": {"href": "https://publications.scilifelab.se/researcher/65325cc227b74704ab85e14385a1673e.json"}}, {"family": "Wolf", "given": "Jochen B W", "initials": "JBW", "orcid": "0000-0002-2958-5183", "researcher": {"href": "https://publications.scilifelab.se/researcher/6c4445d760a64905a9ea6d8664f6a32d.json"}}], "type": "journal article", "published": "2020-08-00", "journal": {"title": "Nat Ecol Evol", "issn": "2397-334X", "volume": "4", "issue": "8", "pages": "1095-1104", "issn-l": "2397-334X"}, "abstract": "The effective size of a population (Ne), which determines its level of neutral variability, is a key evolutionary parameter. Ne can substantially depart from census sizes of present-day breeding populations (NC) as a result of past demographic changes, variation in life-history traits and selection at linked sites. Using genome-wide data we estimated the long-term coalescent Ne for 17 pinniped species represented by 36 population samples (total n = 458 individuals). Ne estimates ranged from 8,936 to 91,178, were highly consistent within (sub)species and showed a strong positive correlation with NC ([Formula: see text] = 0.59; P = 0.0002). Ne/NC ratios were low (mean, 0.31; median, 0.13) and co-varied strongly with demographic history and, to a lesser degree, with species' ecological and life-history variables such as breeding habitat. Residual variation in Ne/NC, after controlling for past demographic fluctuations, contained information about recent population size changes during the Anthropocene. Specifically, species of conservation concern typically had positive residuals indicative of a smaller contemporary NC than would be expected from their long-term Ne. This study highlights the value of comparative population genomic analyses for gauging the evolutionary processes governing genetic variation in natural populations, and provides a framework for identifying populations deserving closer conservation attention.", "doi": "10.1038/s41559-020-1215-5", "pmid": "32514167", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41559-020-1215-5"}], "notes": [], "created": "2020-12-08T23:33:13.775Z", "modified": "2024-01-16T13:48:42.060Z"}, {"entity": "publication", "iuid": "2422b4d991cf4626b7717113f4f2ecc4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2422b4d991cf4626b7717113f4f2ecc4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2422b4d991cf4626b7717113f4f2ecc4"}}, "title": "CELLULOSE SYNTHASE INTERACTING 1 is required for wood mechanics and leaf morphology in aspen.", "authors": [{"family": "B\u00fcnder", "given": "Anne", "initials": "A"}, {"family": "Sundman", "given": "Ola", "initials": "O"}, {"family": "Mahboubi", "given": "Amir", "initials": "A"}, {"family": "Persson", "given": "Staffan", "initials": "S"}, {"family": "Mansfield", "given": "Shawn D", "initials": "SD", "orcid": "0000-0002-0175-554X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a6b6ce31a62344e297c43e4a0f647fdd.json"}}, {"family": "R\u00fcggeberg", "given": "Markus", "initials": "M"}, {"family": "Niittyl\u00e4", "given": "Totte", "initials": "T", "orcid": "0000-0001-8029-1503", "researcher": {"href": "https://publications.scilifelab.se/researcher/f2b8823dc6cf44eaa309fcf157b1f28a.json"}}], "type": "journal article", "published": "2020-08-00", "journal": {"title": "Plant J.", "issn": "1365-313X", "issn-l": "0960-7412", "volume": "103", "issue": "5", "pages": "1858-1868"}, "abstract": "Cellulose microfibrils synthesized by CELLULOSE SYNTHASE COMPLEXES (CSCs) are the main load-bearing polymers in wood. CELLULOSE SYNTHASE INTERACTING1 (CSI1) connects CSCs with cortical microtubules, which align with cellulose microfibrils. Mechanical properties of wood are dependent on cellulose microfibril alignment and structure in the cell walls, but the molecular mechanism(s) defining these features is unknown. Herein, we investigated the role of CSI1 in hybrid aspen (Populus tremula \u00d7 Populus tremuloides) by characterizing transgenic lines with significantly reduced CSI1 transcript abundance. Reduction in leaves (50-80%) caused leaf twisting and misshaped pavement cells, while reduction (70-90%) in developing xylem led to impaired mechanical wood properties evident as a decrease in the elastic modulus and rupture. X-ray diffraction measurements indicate that microfibril angle was not impacted by the altered CSI1 abundance in developing wood fibres. Instead, the augmented wood phenotype of the transgenic trees was associated with a reduced cellulose degree of polymerization. These findings establish a function for CSI1 in wood mechanics and in defining leaf cell shape. Furthermore, the results imply that the microfibril angle in wood is defined by CSI1 independent mechanism(s).", "doi": "10.1111/tpj.14873", "pmid": "32526794", "labels": {"Integrated Microscopy Technologies Ume\u00e5": "Service"}, "xrefs": [], "notes": [], "created": "2022-04-01T15:03:35.012Z", "modified": "2022-04-01T15:03:48.167Z"}, {"entity": "publication", "iuid": "02aba4f1fdd44b4d9243ecec013e23e8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/02aba4f1fdd44b4d9243ecec013e23e8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/02aba4f1fdd44b4d9243ecec013e23e8"}}, "title": "Association between proteomics and obstructive sleep apnea phenotypes in a community-based cohort of women.", "authors": [{"family": "Ljunggren", "given": "Mirjam", "initials": "M", "orcid": "0000-0002-8486-6746", "researcher": {"href": "https://publications.scilifelab.se/researcher/de5ea7d89bed4fe2b28e9c2b6cf9e72a.json"}}, {"family": "Theorell-Hagl\u00f6w", "given": "Jenny", "initials": "J"}, {"family": "Freyhult", "given": "Eva", "initials": "E"}, {"family": "Sahlin", "given": "Carin", "initials": "C"}, {"family": "Franklin", "given": "Karl A", "initials": "KA"}, {"family": "Malinovschi", "given": "Andrei", "initials": "A"}, {"family": "Janson", "given": "Christer", "initials": "C"}, {"family": "Lindberg", "given": "Eva", "initials": "E"}], "type": "journal article", "published": "2020-08-00", "journal": {"title": "J Sleep Res", "issn": "1365-2869", "volume": "29", "issue": "4", "pages": "e13041", "issn-l": null}, "abstract": "Proteomic-based technologies offer new opportunities to identify proteins that might reflect the cardiometabolic stress caused by different aspects of sleep-disordered breathing. We aimed to investigate whether severe obstructive sleep apnea and severe obstructive sleep apnea during rapid eye movement sleep are associated with changed levels of inflammatory and cardiac disease-related proteins in a population-based cohort of women. In the community-based \"Sleep and Health in Women\" (SHE) cohort study, 400 women underwent polysomnography, anthropometric measurements and blood sampling. Two proteomic assays (Olink Proseek\u00ae Inflammation panel and Olink Proseek\u00ae Cardiovascular II panel), each measuring 92 proteins, were analysed in a subsample of 253 women. p-Values were adjusted for multiple testing, with false discovery rate set at 10%. In unadjusted models, 57 proteins were associated with apnea-hypopnea index, 56 proteins with oxygen desaturation index and 64 proteins with rapid eye movement-apnea-hypopnea index. After adjustment for age, body mass index and plate, there were no significant associations between apnea-hypopnea index or oxygen desaturation index and any of the proteins. Severe obstructive sleep apnea during rapid eye movement sleep (rapid eye movement-apnea-hypopnea index \u2265 30) was associated with decreased levels of two anti-inflammatory proteins; Sirt2 (q-value .016) and LAP-TGF-\u03b21 (q-value .016). There was also a negative association between rapid eye movement-apnea-hypopnea index of \u2265 30 and Axin1 (q-value .095), a protein thought to facilitate TGF-\u03b2-signalling. We conclude that severe obstructive sleep apnea during rapid eye movement sleep is associated with low levels of Sirt2, LAP-TGF-\u03b21 and Axin1, anti-inflammatory proteins involved in metabolic regulation and in the atherosclerotic process. For obstructive sleep apnea based on a whole night, the associations with cardiac and inflammatory proteins are weaker, and explained to a large extent by age and body mass index.", "doi": "10.1111/jsr.13041", "pmid": "32267595", "labels": {"Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [], "notes": [], "created": "2020-12-15T14:17:59.859Z", "modified": "2024-01-16T13:48:42.068Z"}, {"entity": "publication", "iuid": "22914a13727a400bbc7bf78b4c9dfd22", "links": {"self": {"href": "https://publications.scilifelab.se/publication/22914a13727a400bbc7bf78b4c9dfd22.json"}, "display": {"href": "https://publications.scilifelab.se/publication/22914a13727a400bbc7bf78b4c9dfd22"}}, "title": "Archaea in boreal Swedish lakes are diverse, dominated by Woesearchaeota and follow deterministic community assembly.", "authors": [{"family": "Juottonen", "given": "Heli", "initials": "H", "orcid": "0000-0003-3769-239X", "researcher": {"href": "https://publications.scilifelab.se/researcher/1af9df805f914a21be382248c50b9d03.json"}}, {"family": "Fontaine", "given": "Laurent", "initials": "L"}, {"family": "Wurzbacher", "given": "Christian", "initials": "C"}, {"family": "Drakare", "given": "Stina", "initials": "S"}, {"family": "Peura", "given": "Sari", "initials": "S", "orcid": "0000-0003-3892-8157", "researcher": {"href": "https://publications.scilifelab.se/researcher/c430ad5c3bd14387b768c588a9b12ce0.json"}}, {"family": "Eiler", "given": "Alexander", "initials": "A", "orcid": "0000-0001-9916-9567", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7286785c9334dcba90273b69f81c018.json"}}], "type": "journal article", "published": "2020-08-00", "journal": {"title": "Environ. Microbiol.", "issn": "1462-2920", "volume": "22", "issue": "8", "pages": "3158-3171", "issn-l": "1462-2912"}, "abstract": "Despite their key role in biogeochemical processes, particularly the methane cycle, archaea are widely underrepresented in molecular surveys because of their lower abundance compared with bacteria and eukaryotes. Here, we use parallel high-resolution small subunit rRNA gene sequencing to explore archaeal diversity in 109 Swedish lakes and correlate archaeal community assembly mechanisms to large-scale latitudinal, climatic (nemoral to arctic) and nutrient (oligotrophic to eutrophic) gradients. Sequencing with universal primers showed the contribution of archaea was on average 0.8% but increased up to 1.5% of the three domains in forest lakes. Archaea-specific sequencing revealed that freshwater archaeal diversity could be partly explained by lake variables associated with nutrient status. Combined with deterministic co-occurrence patterns this finding suggests that ecological drift is overridden by environmental sorting, as well as other deterministic processes such as biogeographic and evolutionary history, leading to lake-specific archaeal biodiversity. Acetoclastic, hydrogenotrophic and methylotrophic methanogens as well as ammonia-oxidizing archaea were frequently detected across the lakes. Archaea-specific sequencing also revealed representatives of Woesearchaeota and other phyla of the DPANN superphylum. This study adds to our understanding of the ecological range of key archaea in freshwaters and links these taxa to hypotheses about processes governing biogeochemical cycles in lakes.", "doi": "10.1111/1462-2920.15058", "pmid": "32372550", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [], "notes": [], "created": "2020-12-08T23:57:02.276Z", "modified": "2024-01-16T13:48:42.081Z"}, {"entity": "publication", "iuid": "f94a8094a9b840e3934058d5f1cfff67", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f94a8094a9b840e3934058d5f1cfff67.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f94a8094a9b840e3934058d5f1cfff67"}}, "title": "Apparent stiffness of vimentin intermediate filaments in living cells and its relation with other cytoskeletal polymers", "authors": [{"family": "Smoler", "given": "Mariano", "initials": "M"}, {"family": "Coceano", "given": "Giovanna", "initials": "G", "orcid": "0000-0001-9391-1476", "researcher": {"href": "https://publications.scilifelab.se/researcher/80a080afe1ee495f9f75f8e6be3ddc10.json"}}, {"family": "Testa", "given": "Ilaria", "initials": "I"}, {"family": "Bruno", "given": "Luciana", "initials": "L"}, {"family": "Levi", "given": "Valeria", "initials": "V"}], "type": "journal-article", "published": "2020-08-00", "journal": {"title": "Biochimica et Biophysica Acta (BBA) - Molecular Cell Research", "issn": "0167-4889", "volume": "1867", "issue": "8", "pages": "118726", "issn-l": null}, "abstract": "The cytoskeleton is a complex network of interconnected biopolymers intimately involved in the generation and transmission of forces. Several mechanical properties of microtubules and actin filaments have been extensively explored in cells. In contrast, intermediate filaments (IFs) received comparatively less attention despite their central role in defining cell shape, motility and adhesion during physiological processes as well as in tumor progression. Here, we explored relevant biophysical properties of vimentin IFs in living cells combining confocal microscopy and a filament tracking routine that allows localizing filaments with ~20 nm precision. A Fourier-based analysis showed that IFs curvatures followed a thermal-like behavior characterized by an apparent persistence length (lp*) similar to that measured in aqueous solution. Additionally, we determined that certain perturbations of the cytoskeleton affect lp* and the lateral mobility of IFs as assessed in cells in which either the microtubule dynamic instability was reduced or actin filaments were partially depolymerized. Our results provide relevant clues on how vimentin IFs mechanically couple with microtubules and actin filaments in cells and support a role of this network in the response to mechanical stress.", "doi": "10.1016/j.bbamcr.2020.118726", "pmid": "32320724", "labels": {"Integrated Microscopy Technologies Stockholm": "Service"}, "xrefs": [{"db": "pii", "key": "S0167-4889(20)30084-7"}], "notes": [], "created": "2021-09-03T11:08:40.963Z", "modified": "2023-06-19T11:06:42.416Z"}, {"entity": "publication", "iuid": "648b4af06fe24d8a9f646def6e1e9115", "links": {"self": {"href": "https://publications.scilifelab.se/publication/648b4af06fe24d8a9f646def6e1e9115.json"}, "display": {"href": "https://publications.scilifelab.se/publication/648b4af06fe24d8a9f646def6e1e9115"}}, "title": "A robust and versatile method for production and purification of large-scale RNA samples for structural biology.", "authors": [{"family": "Karlsson", "given": "Hampus", "initials": "H"}, {"family": "Baronti", "given": "Lorenzo", "initials": "L"}, {"family": "Petzold", "given": "Katja", "initials": "K"}], "type": "journal article", "published": "2020-08-00", "journal": {"title": "RNA", "issn": "1469-9001", "volume": "26", "issue": "8", "pages": "1023-1037", "issn-l": "1355-8382"}, "abstract": "Recent findings in genome-wide transcriptomics revealed that RNAs are involved in almost every biological process, across all domains of life. The characterization of native RNAs of unknown function and structure is particularly challenging due to their typical low abundance in the cell and the inherent sensitivity toward ubiquitous RNA degrading enzymes. Therefore, robust in vitro synthesis and extensive work-up methods are often needed to obtain samples amenable for biochemical, biophysical, and structural studies. Here, we present a protocol that combines the most recent advances in T7 in vitro transcription methodology with reverse phase ion pairing and ion exchange HPLC purification of RNAs for the production of yield-optimized large-scale samples. The method is easy to follow, robust and suitable for users with little or no experience within the field of biochemistry or chromatography. The complete execution of this method, for example, for production of isotopically labeled NMR samples, can be performed in less than a week.", "doi": "10.1261/rna.075697.120", "pmid": "32354720", "labels": {"Protein Science Facility (PSF)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7373988"}, {"db": "pii", "key": "rna.075697.120"}, {"db": "medline", "key": "9509184"}], "notes": [], "created": "2024-04-03T14:25:24.689Z", "modified": "2024-04-03T14:25:24.694Z"}, {"entity": "publication", "iuid": "c8306d328e0642fb94ee6dfdde1c5505", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c8306d328e0642fb94ee6dfdde1c5505.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c8306d328e0642fb94ee6dfdde1c5505"}}, "title": "A novel recombinant expression and purification approach for the full-length anti-apoptotic membrane protein Bcl-2.", "authors": [{"family": "\u00c5d\u00e9n", "given": "J\u00f6rgen", "initials": "J"}, {"family": "Mushtaq", "given": "Ameeq Ul", "initials": "AU"}, {"family": "Dingeldein", "given": "Artur", "initials": "A"}, {"family": "Wallgren", "given": "Marcus", "initials": "M"}, {"family": "Gr\u00f6bner", "given": "Gerhard", "initials": "G", "orcid": "0000-0001-7380-8797", "researcher": {"href": "https://publications.scilifelab.se/researcher/85bd86ebc85d4653bc880bc9be25bc80.json"}}], "type": "journal article", "published": "2020-08-00", "journal": {"title": "Protein Expression and Purification", "issn": "1096-0279", "volume": "172", "issue": null, "pages": "105628", "issn-l": "1046-5928"}, "abstract": "Programmed cell death (apoptosis) is an essential mechanism in life that tightly regulates embryogenesis and removal of harmful cells. Besides an extrinsic pathway, an intrinsic (mitochondrial) apoptotic pathway exists where mitochondria are actively involved in cellular clearance in response to internal stress signals. Pro-apoptotic (death) and anti-apoptotic (survival) members of the B cell CLL/lymphoma-2 (Bcl-2) protein family meet at the mitochondrion's surface where they accurately regulate apoptosis. Overexpression of the anti-apoptotic Bcl-2 protein is a hallmark for many types of cancers and in particular for many treatment resistant tumors. Bcl-2 is a membrane protein residing in the mitochondrial outer membrane. Due to its typical membrane protein features including very limited solubility, it is difficult to express and to purify. Therefore, most biophysical and structural studies have used truncated, soluble versions. However, to understand its membrane-coupled function and structure, access to sufficient amount of full-length human Bcl-2 protein is a necessity. Here, we present a novel, E. coli based approach for expression and purification of preparative amounts of the full-length human isoform 2 of Bcl-2 (Bcl-2(2)), solubilized in detergent micelles, which allows for easy exchange of the detergent.", "doi": "10.1016/j.pep.2020.105628", "pmid": "32209420", "labels": {"Swedish NMR Centre": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S1046-5928(20)30128-5"}], "notes": [], "created": "2020-03-30T11:34:44.377Z", "modified": "2025-10-17T13:03:56.671Z"}, {"entity": "publication", "iuid": "4a9b528a26aa47e38f232b961ded646c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4a9b528a26aa47e38f232b961ded646c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4a9b528a26aa47e38f232b961ded646c"}}, "title": "A decade of epigenetic change in aging twins: Genetic and environmental contributions to longitudinal DNA methylation.", "authors": [{"family": "Reynolds", "given": "Chandra A", "initials": "CA", "orcid": "0000-0001-6502-7173", "researcher": {"href": "https://publications.scilifelab.se/researcher/6b7cd2b82d81463c8dd3f13c4d75ab6f.json"}}, {"family": "Tan", "given": "Qihua", "initials": "Q"}, {"family": "Munoz", "given": "Elizabeth", "initials": "E"}, {"family": "Jylh\u00e4v\u00e4", "given": "Juulia", "initials": "J"}, {"family": "Hjelmborg", "given": "Jacob", "initials": "J"}, {"family": "Christiansen", "given": "Lene", "initials": "L"}, {"family": "H\u00e4gg", "given": "Sara", "initials": "S", "orcid": "0000-0002-2452-1500", "researcher": {"href": "https://publications.scilifelab.se/researcher/e1d010dfe5d84a33b6a6c7ec815ca3dc.json"}}, {"family": "Pedersen", "given": "Nancy L", "initials": "NL"}], "type": "journal article", "published": "2020-08-00", "journal": {"title": "Aging Cell", "issn": "1474-9726", "volume": "19", "issue": "8", "pages": "e13197", "issn-l": "1474-9718"}, "abstract": "Epigenetic changes may result from the interplay of environmental exposures and genetic influences and contribute to differences in age-related disease, disability, and mortality risk. However, the etiologies contributing to stability and change in DNA methylation have rarely been examined longitudinally.\n\nWe considered DNA methylation in whole blood leukocyte DNA across a 10-year span in two samples of same-sex aging twins: (a) Swedish Adoption Twin Study of Aging (SATSA; N = 53 pairs, 53% female; 62.9 and 72.5 years, SD = 7.2 years); (b) Longitudinal Study of Aging Danish Twins (LSADT; N = 43 pairs, 72% female, 76.2 and 86.1 years, SD=1.8 years). Joint biometrical analyses were conducted on 358,836 methylation probes in common. Bivariate twin models were fitted, adjusting for age, sex, and country.\n\nOverall, results suggest genetic contributions to DNA methylation across 358,836 sites tended to be small and lessen across 10 years (broad heritability M = 23.8% and 18.0%) but contributed to stability across time while person-specific factors explained emergent influences across the decade. Aging-specific sites identified from prior EWAS and methylation age clocks were more heritable than background sites. The 5037 sites that showed the greatest heritable/familial-environmental influences (p < 1E-07) were enriched for immune and inflammation pathways while 2020 low stability sites showed enrichment in stress-related pathways.\n\nAcross time, stability in methylation is primarily due to genetic contributions, while novel experiences and exposures contribute to methylation differences. Elevated genetic contributions at age-related methylation sites suggest that adaptions to aging and senescence may be differentially impacted by genetic background.", "doi": "10.1111/acel.13197", "pmid": "32710526", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7431820"}], "notes": [], "created": "2020-08-04T14:50:02.748Z", "modified": "2024-01-16T13:48:42.094Z"}, {"entity": "publication", "iuid": "5446fda678b44232a03fb58e253bbb2f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5446fda678b44232a03fb58e253bbb2f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5446fda678b44232a03fb58e253bbb2f"}}, "title": "A 3D Cell Culture Model Identifies Wnt/\u03b2-Catenin Mediated Inhibition of p53 as a Critical Step during Human Hepatocyte Regeneration.", "authors": [{"family": "Oliva-Vilarnau", "given": "Nuria", "initials": "N", "orcid": "0000-0002-3083-6701", "researcher": {"href": "https://publications.scilifelab.se/researcher/29e93281648540e9ae407c2cefbc542e.json"}}, {"family": "Vorrink", "given": "Sabine U", "initials": "SU"}, {"family": "Ingelman-Sundberg", "given": "Magnus", "initials": "M"}, {"family": "Lauschke", "given": "Volker M", "initials": "VM", "orcid": "0000-0002-1140-6204", "researcher": {"href": "https://publications.scilifelab.se/researcher/29c123916fbf4948a911560c1a259496.json"}}], "type": "journal article", "published": "2020-08-00", "journal": {"title": "Adv Sci (Weinh)", "issn": "2198-3844", "volume": "7", "issue": "15", "pages": "2000248", "issn-l": null}, "abstract": "The liver is a highly regenerative organ. While mature hepatocytes under homeostatic conditions are largely quiescent, upon injury, they rapidly enter the cell cycle to recover the damaged tissue. In rodents, a variety of injury models have provided important insights into the molecular underpinnings that govern the proliferative activation of quiescent hepatocytes. However, little is known about the molecular mechanisms of human hepatocyte regeneration and experimental methods to expand primary human hepatocytes (PHH). Here, a 3D spheroid model of PHH is established to study hepatocyte regeneration and integrative time-lapse multi-omics analyses show that upon isolation from the native liver PHH acquire a regenerative phenotype, as seen in vivo upon partial hepatectomy. However, proliferation is limited. By analyzing global promoter motif activities, it is predicted that activation of Wnt/\u03b2-catenin and inhibition of p53 signaling are critical factors required for human hepatocyte proliferation. Functional validations reveal that activation of Wnt signaling through external cues alone is sufficient to inhibit p53 and its proliferative senescence-inducing target PAI1 (SERPINE1) and drive proliferation of >50% of all PHH. A scalable 3D culture model is established to study the molecular and cellular biology of human hepatocyte regeneration. By using this model, an essential role of Wnt/\u03b2-catenin signaling during human hepatocyte regeneration is identified.", "doi": "10.1002/advs.202000248", "pmid": "32775153", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pii", "key": "ADVS1906"}, {"db": "pmc", "key": "PMC7404138"}], "notes": [], "created": "2020-12-07T16:34:35.595Z", "modified": "2022-03-29T13:44:10.380Z"}, {"entity": "publication", "iuid": "d191a7af04da4afea9d0e9e07fe20a75", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d191a7af04da4afea9d0e9e07fe20a75.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d191a7af04da4afea9d0e9e07fe20a75"}}, "title": "The genetic regulation of size variation in the transcriptome of the cerebrum in the chicken and its role in domestication and brain size evolution.", "authors": [{"family": "H\u00f6glund", "given": "Andrey", "initials": "A"}, {"family": "Strempfl", "given": "Katharina", "initials": "K"}, {"family": "Fogelholm", "given": "Jesper", "initials": "J"}, {"family": "Wright", "given": "Dominic", "initials": "D"}, {"family": "Henriksen", "given": "Rie", "initials": "R", "orcid": "0000-0002-7290-6376", "researcher": {"href": "https://publications.scilifelab.se/researcher/ca679685607b4187bffa818ee1168c81.json"}}], "type": "journal article", "published": "2020-07-29", "journal": {"title": "BMC Genomics", "issn": "1471-2164", "volume": "21", "issue": "1", "pages": "518", "issn-l": "1471-2164"}, "abstract": "Large difference in cerebrum size exist between avian species and populations of the same species and is believed to reflect differences in processing power, i.e. in the speed and efficiency of processing information in this brain region. During domestication chickens developed a larger cerebrum compared to their wild progenitor, the Red jungle fowl. The underlying mechanisms that control cerebrum size and the extent to which genetic regulation is similar across brain regions is not well understood. In this study, we combine measurement of cerebrum size with genome-wide genetical genomics analysis to identify the genetic architecture of the cerebrum, as well as compare the regulation of gene expression in this brain region with gene expression in other regions of the brain (the hypothalamus) and somatic tissue (liver).\n\nWe identify one candidate gene that putatively regulates cerebrum size (MTF2) as well as a large number of eQTL that regulate the transcriptome in cerebrum tissue, with the majority of these eQTL being trans-acting. The overall regulation of gene expression variation in the cerebrum was markedly different to the hypothalamus, with relatively few eQTL in common. In comparison, the cerebrum tissue shared more eQTL with a distant tissue (liver) than with a neighboring tissue (hypothalamus).\n\nThe candidate gene for cerebrum size (MTF2) has previously been linked to brain development making it a good candidate for further investigation as a regulator of inter-population variation in cerebrum size. The lack of shared eQTL between the two brain regions implies that genetic regulation of gene expression appears to be relatively independent between the two brain regions and suggest that coevolution between these two brain regions might be more functionally driven than developmental. These findings have relevance for current brain size evolution theories.", "doi": "10.1186/s12864-020-06908-0", "pmid": "32727510", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12864-020-06908-0"}, {"db": "pmc", "key": "PMC7392834"}], "notes": [], "created": "2020-08-04T14:50:06.953Z", "modified": "2024-01-16T13:48:42.102Z"}, {"entity": "publication", "iuid": "80d309ad52724e478307f7267291dec2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/80d309ad52724e478307f7267291dec2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/80d309ad52724e478307f7267291dec2"}}, "title": "First evidence of microbial wood degradation in the coastal waters of the Antarctic.", "authors": [{"family": "Bj\u00f6rdal", "given": "Charlotte G", "initials": "CG"}, {"family": "Dayton", "given": "Paul K", "initials": "PK"}], "type": "journal article", "published": "2020-07-29", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "12774", "issn-l": "2045-2322"}, "abstract": "Wood submerged in saline and oxygenated marine waters worldwide is efficiently degraded by crustaceans and molluscs. Nevertheless, in the cold coastal waters of the Antarctic, these degraders seem to be absent and no evidence of other wood-degrading organisms has been reported so far. Here we examine long-term exposed anthropogenic wood material (Douglas Fir) collected at the seafloor close to McMurdo station, Antarctica. We used light and scanning electron microscopy and demonstrate that two types of specialized lignocellulolytic microbes-soft rot fungi and tunnelling bacteria-are active and degrade wood in this extreme environment. Fungal decay dominates and hyphae penetrate the outer 2-4 mm of the wood surface. Decay rates observed are about two orders of magnitude lower than normal. The fungi and bacteria, as well as their respective cavities and tunnels, are slightly smaller than normal, which might represent an adaptation to the extreme cold environment. Our results establish that there is ongoing wood degradation also in the Antarctic, albeit at a vastly reduced rate compared to warmer environments. Historical shipwrecks resting on the seafloor are most likely still in good condition, although surface details such as wood carvings, tool marks, and paint slowly disintegrate due to microbial decay.", "doi": "10.1038/s41598-020-68613-y", "pmid": "32728072", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7391713"}, {"db": "pii", "key": "10.1038/s41598-020-68613-y"}], "notes": [], "created": "2023-02-16T08:04:18.196Z", "modified": "2023-02-16T08:04:18.198Z"}, {"entity": "publication", "iuid": "4b7619de4223442c97116b35b0c7402c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4b7619de4223442c97116b35b0c7402c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4b7619de4223442c97116b35b0c7402c"}}, "title": "Extracellular vesicles from human mesenchymal stem cells expedite chondrogenesis in 3D human degenerative disc cell cultures.", "authors": [{"family": "Hingert", "given": "Daphne", "initials": "D", "orcid": "0000-0002-8917-4458", "researcher": {"href": "https://publications.scilifelab.se/researcher/39bff3945f184267b4360bb086322e3c.json"}}, {"family": "Ekstr\u00f6m", "given": "Karin", "initials": "K"}, {"family": "Aldridge", "given": "Jonathan", "initials": "J"}, {"family": "Crescitelli", "given": "Rosella", "initials": "R"}, {"family": "Brisby", "given": "Helena", "initials": "H"}], "type": "journal article", "published": "2020-07-29", "journal": {"title": "Stem Cell Res Ther", "issn": "1757-6512", "volume": "11", "issue": "1", "pages": "323", "issn-l": "1757-6512"}, "abstract": "Extracellular vesicles (EVs) from human mesenchymal stem cells (hMSCs) are known to be mediators of intercellular communication and have been suggested as possible therapeutic agents in many diseases. Their potential use in intervertebral disc (IVD) degeneration associated with low back pain (LBP) is yet to be explored. Since LBP affects more than 85% of the western population resulting in high socioeconomic consequences, there is a demand for exploring new and possibly mini-invasive treatment alternatives. In this study, the effect of hMSC-derived small EVs (sEVs) on degenerated disc cells (DCs) isolated from patients with degenerative discs and chronic LBP was investigated in a 3D in vitro model.\n\nhMSCs were isolated from bone marrow aspirate, and EVs were isolated from conditioned media of the hMSCs by differential centrifugation and filtration. 3D pellet cultures of DCs were stimulated with the sEVs at 5 \u00d7 1010 vesicles/ml concentration for 28 days and compared to control. The pellets were harvested at days 7, 14, and 28 and evaluated for cell proliferation, viability, ECM production, apoptotic activity, chondrogenesis, and cytokine secretions.\n\nThe findings demonstrated that treatment with sEVs from hMSCs resulted in more than 50% increase in cell proliferation and decrease in cellular apoptosis in degenerated DCs from this patient group. ECM production was also observed as early as in day 7 and was more than three times higher in the sEV-treated DC pellets compared to control cultures. Further, sEV treatment suppressed secretion of MMP-1 in the DCs.\n\nhMSC-derived sEVs improved cell viability and expedited chondrogenesis in DCs from degenerated IVDs. These findings open up for new tissue regeneration treatment strategies to be developed for degenerative disorders of the spine.", "doi": "10.1186/s13287-020-01832-2", "pmid": "32727623", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7391655"}, {"db": "pii", "key": "10.1186/s13287-020-01832-2"}], "notes": [], "created": "2023-02-16T08:07:16.860Z", "modified": "2023-02-16T08:07:17.111Z"}, {"entity": "publication", "iuid": "d0290e65d9f045e798c9c885b9c72cbd", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d0290e65d9f045e798c9c885b9c72cbd.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d0290e65d9f045e798c9c885b9c72cbd"}}, "title": "Detection of leukemia gene fusions by targeted RNA-sequencing in routine diagnostics.", "authors": [{"family": "Engvall", "given": "Marie", "initials": "M", "orcid": "0000-0002-7394-9191", "researcher": {"href": "https://publications.scilifelab.se/researcher/0be7a9a5a518448ba7afb6f7a2cb3ca1.json"}}, {"family": "Cahill", "given": "Nicola", "initials": "N"}, {"family": "Jonsson", "given": "Britt-Inger", "initials": "BI"}, {"family": "H\u00f6glund", "given": "Martin", "initials": "M"}, {"family": "Hallb\u00f6\u00f6k", "given": "Helene", "initials": "H"}, {"family": "Cavelier", "given": "Lucia", "initials": "L", "orcid": "0009-0003-8195-370X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f01226edb140436da0c9d166c1f5fe51.json"}}], "type": "journal article", "published": "2020-07-29", "journal": {"title": "BMC Med Genomics", "issn": "1755-8794", "volume": "13", "issue": "1", "pages": "106", "issn-l": "1755-8794"}, "abstract": "We have evaluated an NGS-based method to detect recurrent gene fusions of diagnostic and prognostic importance in hematological malignancies. Our goal was to achieve a highly specific assay with a simple workflow, short turnaround time and low cost.\n\nThe assay uses a commercially available anchored multiplex PCR panel for target enrichment and library preparation, followed by sequencing using a MiSeq instrument. The panel includes all recurrent gene fusions in AML and ALL and is designed to detect gene-specific fusions without prior knowledge of the partner sequence or specific break points. Diagnostic RNA samples from 27 cases with hematological malignancies encompassing 23 different transcript variants were analyzed. In addition, 12 cases from a validation cohort were assessed.\n\nAll known fusion transcripts were identified with a high degree of confidence, with a large number of reads covering the breakpoints. Importantly, we could identify gene fusions where conventional methods had failed due to cryptic rearrangements or rare fusion partners. The newly-identified fusion partners were verified by RT-PCR and transcript-specific qPCR was designed for patient-specific follow-up. In addition, 12 cases were correctly assessed in a blind test, without prior knowledge of molecular cytogenetics or diagnosis.\n\nIn summary, our results demonstrate that targeted RNA sequencing using anchored multiplex PCR can be implemented in a clinical laboratory for the detection of recurrent and rare gene fusions in hematological diagnostic samples.", "doi": "10.1186/s12920-020-00739-4", "pmid": "32727569", "labels": {"Clinical Genomics Uppsala": "Technology development", "Clinical Genomics": "Technology development"}, "xrefs": [{"db": "pii", "key": "10.1186/s12920-020-00739-4"}, {"db": "pmc", "key": "PMC7388219"}], "notes": [], "created": "2020-11-06T13:03:04.566Z", "modified": "2021-11-10T12:48:54.750Z"}, {"entity": "publication", "iuid": "800346346d7a4a988909546711807aeb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/800346346d7a4a988909546711807aeb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/800346346d7a4a988909546711807aeb"}}, "title": "Combining transcriptomics and genetic linkage based information to identify candidate genes associated with Heterobasidion-resistance in Norway spruce.", "authors": [{"family": "Chaudhary", "given": "Rajiv", "initials": "R"}, {"family": "Lund\u00e9n", "given": "Karl", "initials": "K"}, {"family": "Dalman", "given": "Kerstin", "initials": "K"}, {"family": "Dubey", "given": "Mukesh", "initials": "M"}, {"family": "Nemesio-Gorriz", "given": "Miguel", "initials": "M"}, {"family": "Karlsson", "given": "Bo", "initials": "B"}, {"family": "Stenlid", "given": "Jan", "initials": "J"}, {"family": "Elfstrand", "given": "Malin", "initials": "M"}], "type": "journal article", "published": "2020-07-29", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "12711", "issn-l": "2045-2322"}, "abstract": "The Heterobasidion annosum s.l species complex comprises the most damaging forest pathogens to Norway spruce. We revisited previously identified Quantitative Trait Loci (QTLs) related to Heterobasidion-resistance in Norway spruce to identify candidate genes associated with these QTLs. We identified 329 candidate genes associated with the resistance QTLs using a gene-based composite map for Pinaceae. To evaluate the transcriptional responses of these candidate genes to H. parviporum, we inoculated Norway spruce plants and sequenced the transcriptome of the interaction at 3 and 7 days post inoculation. Out of 298 expressed candidate genes 124 were differentially expressed between inoculation and wounding control treatment. Interestingly, PaNAC04 and two of its paralogs in the subgroup III-3 of the NAC family transcription factors were found to be associated with one of the QTLs and was also highly induced in response to H. parviporum. These genes are possibly involved in the regulation of biosynthesis of flavonoid compounds. Furthermore, several of the differentially expressed candidate genes were associated with the phenylpropanoid pathway including a phenylalanine ammonia-lyase, a cinnamoyl-CoA reductase, a caffeoyl-CoA O-methyltransferase and a PgMYB11-like transcription factor gene. Combining transcriptome and genetic linkage analyses can help identifying candidate genes for functional studies and molecular breeding in non-model species.", "doi": "10.1038/s41598-020-69386-0", "pmid": "32728135", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-69386-0"}, {"db": "pmc", "key": "PMC7391732"}], "notes": [], "created": "2020-12-08T23:27:29.107Z", "modified": "2024-01-16T13:48:42.109Z"}, {"entity": "publication", "iuid": "37bb53f5ef1a4d17aa606c91b42c475a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/37bb53f5ef1a4d17aa606c91b42c475a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/37bb53f5ef1a4d17aa606c91b42c475a"}}, "title": "Prototypical pacemaker neurons interact with the resident microbiota.", "authors": [{"family": "Klimovich", "given": "Alexander", "initials": "A", "orcid": "0000-0003-1764-0613", "researcher": {"href": "https://publications.scilifelab.se/researcher/9bdf3caf5f06422787d87e2d1cc94765.json"}}, {"family": "Giacomello", "given": "Stefania", "initials": "S", "orcid": "0000-0003-0738-1574", "researcher": {"href": "https://publications.scilifelab.se/researcher/8499e792cc394c42b4240ef5fb3fd06c.json"}}, {"family": "Bj\u00f6rklund", "given": "\u00c5sa", "initials": "\u00c5"}, {"family": "Faure", "given": "Louis", "initials": "L", "orcid": "0000-0003-4621-586X", "researcher": {"href": "https://publications.scilifelab.se/researcher/bbf218e53c854d69a1b474a61480c33f.json"}}, {"family": "Kaucka", "given": "Marketa", "initials": "M"}, {"family": "Giez", "given": "Christoph", "initials": "C", "orcid": "0000-0002-8101-6498", "researcher": {"href": "https://publications.scilifelab.se/researcher/0e5dd22b6abd4b1293298bd4a99c9b39.json"}}, {"family": "Murillo-Rincon", "given": "Andrea P", "initials": "AP"}, {"family": "Matt", "given": "Ann-Sophie", "initials": "AS"}, {"family": "Willoweit-Ohl", "given": "Doris", "initials": "D", "orcid": "0000-0003-1693-5057", "researcher": {"href": "https://publications.scilifelab.se/researcher/45dbbd5db8324f2eab620af47eaea7d8.json"}}, {"family": "Crupi", "given": "Gabriele", "initials": "G"}, {"family": "de Anda", "given": "Jaime", "initials": "J", "orcid": "0000-0003-2129-0775", "researcher": {"href": "https://publications.scilifelab.se/researcher/f887c2a5655643779c36f5e7e0a332b8.json"}}, {"family": "Wong", "given": "Gerard C L", "initials": "GCL", "orcid": "0000-0003-0893-6383", "researcher": {"href": "https://publications.scilifelab.se/researcher/a4e82c656a3b41388b30db8bcf45ad61.json"}}, {"family": "D'Amato", "given": "Mauro", "initials": "M", "orcid": "0000-0003-2743-5197", "researcher": {"href": "https://publications.scilifelab.se/researcher/538f828b3e61418fad903e0184c545cd.json"}}, {"family": "Adameyko", "given": "Igor", "initials": "I", "orcid": "0000-0001-5471-0356", "researcher": {"href": "https://publications.scilifelab.se/researcher/346f484a56cb4ad5b866b194ccd44e4f.json"}}, {"family": "Bosch", "given": "Thomas C G", "initials": "TCG", "orcid": "0000-0002-9488-5545", "researcher": {"href": "https://publications.scilifelab.se/researcher/4605ee2352c74a58807a7c847379a5aa.json"}}], "type": "journal article", "published": "2020-07-28", "journal": {"title": "Proc. Natl. Acad. Sci. U.S.A.", "issn": "1091-6490", "volume": "117", "issue": "30", "pages": "17854-17863", "issn-l": "0027-8424"}, "abstract": "Pacemaker neurons exert control over neuronal circuit function by their intrinsic ability to generate rhythmic bursts of action potential. Recent work has identified rhythmic gut contractions in human, mice, and hydra to be dependent on both neurons and the resident microbiota. However, little is known about the evolutionary origin of these neurons and their interaction with microbes. In this study, we identified and functionally characterized prototypical ANO/SCN/TRPM ion channel-expressing pacemaker cells in the basal metazoan Hydra by using a combination of single-cell transcriptomics, immunochemistry, and functional experiments. Unexpectedly, these prototypical pacemaker neurons express a rich set of immune-related genes mediating their interaction with the microbial environment. Furthermore, functional experiments gave a strong support to a model of the evolutionary emergence of pacemaker cells as neurons using components of innate immunity to interact with the microbial environment and ion channels to generate rhythmic contractions.", "doi": "10.1073/pnas.1920469117", "pmid": "32647059", "labels": {"Bioinformatics Long-term Support WABI": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "1920469117"}, {"db": "pmc", "key": "PMC7395494"}], "notes": [], "created": "2020-09-28T07:52:51.511Z", "modified": "2024-01-16T13:48:42.117Z"}, {"entity": "publication", "iuid": "8e7a9d42330c43e1965e9b1e2bc5fb5a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8e7a9d42330c43e1965e9b1e2bc5fb5a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8e7a9d42330c43e1965e9b1e2bc5fb5a"}}, "title": "Early Pleistocene origin and extensive intra-species diversity of the extinct cave lion.", "authors": [{"family": "Stanton", "given": "David W G", "initials": "DWG"}, {"family": "Alberti", "given": "Federica", "initials": "F"}, {"family": "Plotnikov", "given": "Valery", "initials": "V"}, {"family": "Androsov", "given": "Semyon", "initials": "S"}, {"family": "Grigoriev", "given": "Semyon", "initials": "S"}, {"family": "Fedorov", "given": "Sergey", "initials": "S"}, {"family": "Kosintsev", "given": "Pavel", "initials": "P"}, {"family": "Nagel", "given": "Doris", "initials": "D"}, {"family": "Vartanyan", "given": "Sergey", "initials": "S"}, {"family": "Barnes", "given": "Ian", "initials": "I"}, {"family": "Barnett", "given": "Ross", "initials": "R"}, {"family": "Ersmark", "given": "Erik", "initials": "E"}, {"family": "D\u00f6ppes", "given": "Doris", "initials": "D"}, {"family": "Germonpr\u00e9", "given": "Mietje", "initials": "M"}, {"family": "Hofreiter", "given": "Michael", "initials": "M"}, {"family": "Rosendahl", "given": "Wilfried", "initials": "W"}, {"family": "Skoglund", "given": "Pontus", "initials": "P"}, {"family": "Dal\u00e9n", "given": "Love", "initials": "L", "orcid": "0000-0001-8270-7613", "researcher": {"href": "https://publications.scilifelab.se/researcher/48ecf726779249ac9d12f4f7a1cc62bf.json"}}], "type": "journal article", "published": "2020-07-28", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "12621", "issn-l": "2045-2322"}, "abstract": "The cave lion is an extinct felid that was widespread across the Holarctic throughout the Late Pleistocene. Its closest extant relative is the lion (Panthera leo), but the timing of the divergence between these two taxa, as well as their taxonomic ranking are contentious. In this study we analyse 31 mitochondrial genome sequences from cave lion individuals that, through a combination of 14C and genetic tip dating, are estimated to be from dates extending well into the mid-Pleistocene. We identified two deeply diverged and well-supported reciprocally monophyletic mitogenome clades in the cave lion, and an additional third distinct lineage represented by a single individual. One of these clades was restricted to Beringia while the other was prevalent across western Eurasia. These observed clade distributions are in line with previous observations that Beringian and European cave lions were morphologically distinct. The divergence dates for these lineages are estimated to be far older than those between extant lions subspecies. By combining our radiocarbon tip-dates with a split time prior that takes into account the most up-to-date fossil stem calibrations, we estimated the mitochondrial DNA divergence between cave lions and lions to be 1.85 Million ya (95% 0.52- 2.91 Mya). Taken together, these results support previous hypotheses that cave lions existed as at least two subspecies during the Pleistocene, and that lions and cave lions were distinct species.", "doi": "10.1038/s41598-020-69474-1", "pmid": "32724178", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-69474-1"}, {"db": "pmc", "key": "PMC7387438"}], "notes": [], "created": "2020-12-07T16:29:55.459Z", "modified": "2021-11-10T12:48:58.284Z"}, {"entity": "publication", "iuid": "992af96f40714b66ac12fbe6718cbcfa", "links": {"self": {"href": "https://publications.scilifelab.se/publication/992af96f40714b66ac12fbe6718cbcfa.json"}, "display": {"href": "https://publications.scilifelab.se/publication/992af96f40714b66ac12fbe6718cbcfa"}}, "title": "A Transmembrane Crenarchaeal Mannosyltransferase Is Involved in N-Glycan Biosynthesis and Displays an Unexpected Minimal Cellulose-Synthase-like Fold.", "authors": [{"family": "Gandini", "given": "Rosaria", "initials": "R"}, {"family": "Reichenbach", "given": "Tom", "initials": "T"}, {"family": "Spadiut", "given": "Oliver", "initials": "O"}, {"family": "Tan", "given": "Tien-Chye", "initials": "TC"}, {"family": "Kalyani", "given": "Dayanand C", "initials": "DC"}, {"family": "Divne", "given": "Christina", "initials": "C"}], "type": "journal article", "published": "2020-07-24", "journal": {"title": "J. Mol. Biol.", "issn": "1089-8638", "volume": "432", "issue": "16", "pages": "4658-4672", "issn-l": "0022-2836"}, "abstract": "Protein glycosylation constitutes a critical post-translational modification that supports a vast number of biological functions in living organisms across all domains of life. A seemingly boundless number of enzymes, glycosyltransferases, are involved in the biosynthesis of these protein-linked glycans. Few glycan-biosynthetic glycosyltransferases have been characterized in vitro, mainly due to the majority being integral membrane proteins and the paucity of relevant acceptor substrates. The crenarchaeote Pyrobaculum calidifontis belongs to the TACK superphylum of archaea (Thaumarchaeota, Aigarchaeota, Crenarchaeota, Korarchaeota) that has been proposed as an eukaryotic ancestor. In archaea, N-glycans are mainly found on cell envelope surface-layer proteins, archaeal flagellins and pili. Archaeal N-glycans are distinct from those of eukaryotes, but one noteworthy exception is the high-mannose N-glycan produced by P. calidifontis, which is similar in sugar composition to the eukaryotic counterpart. Here, we present the characterization and crystal structure of the first member of a crenarchaeal membrane glycosyltransferase, PcManGT. We show that the enzyme is a GDP-, dolichylphosphate-, and manganese-dependent mannosyltransferase. The membrane domain of PcManGT includes three transmembrane helices that topologically coincide with \"half\" of the six-transmembrane helix cellulose-binding tunnel in Rhodobacter spheroides cellulose synthase BcsA. Conceivably, this \"half tunnel\" would be suitable for binding the dolichylphosphate-linked acceptor substrate. The PcManGT gene (Pcal_0472) is located in a large gene cluster comprising 14 genes of which 6 genes code for glycosyltransferases, and we hypothesize that this cluster may constitute a crenarchaeal N-glycosylation (PNG) gene cluster.", "doi": "10.1016/j.jmb.2020.06.016", "pmid": "32569746", "labels": {"Protein Science Facility (PSF)": "Service"}, "xrefs": [{"db": "pii", "key": "S0022-2836(20)30412-5"}], "notes": [], "created": "2020-10-03T15:18:58.327Z", "modified": "2021-11-10T12:49:01.639Z"}, {"entity": "publication", "iuid": "8d1eb5eb8a724e6eb65c2e12e279b329", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8d1eb5eb8a724e6eb65c2e12e279b329.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8d1eb5eb8a724e6eb65c2e12e279b329"}}, "title": "Recording In-Cell NMR-Spectra in Living Mammalian Cells.", "authors": [{"family": "Mate\u010dko-Burmann", "given": "Irena", "initials": "I"}, {"family": "Burmann", "given": "Bj\u00f6rn M", "initials": "BM"}], "type": "journal article", "published": "2020-07-23", "journal": {"title": "Methods Mol. Biol.", "issn": "1940-6029", "volume": "2141", "issue": null, "pages": "857-871", "issn-l": "1064-3745"}, "abstract": "At the foundation of many cellular processes as well as a large number of diseases is the (mis)folding of important intrinsically disordered proteins (IDPs). Despite tremendous scientific efforts, the factors driving their structural changes within the cellular context remain poorly understood. In-cell NMR spectroscopy enables investigation of IDPs directly in the living eukaryotic cell enabling investigation of its intermolecular interactions and ensuing modifications at an unprecedented atomic resolution. In the following protocol, we describe how to prepare in-cell NMR samples of IDPs within eukaryotic cells and how to measure these in-cell NMR samples of an IDP in its natural environment, the living mammalian cell. Furthermore, we outline a procedure to assess the intracellular recombinant protein concentration of the studied IDP based on in-cell NMR methods. We use \u03b1-synuclein as a model protein, but the presented approach is highly modular and therefore should be easily adapted and altered to the desired needs for the studies of different IDPs.", "doi": "10.1007/978-1-0716-0524-0_44", "pmid": "32696393", "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [], "notes": [], "created": "2020-12-11T09:08:06.143Z", "modified": "2025-10-17T13:03:56.691Z"}, {"entity": "publication", "iuid": "ecc643eb325e459ba96278ec8f94c919", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ecc643eb325e459ba96278ec8f94c919.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ecc643eb325e459ba96278ec8f94c919"}}, "title": "Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma.", "authors": [{"family": "Ji", "given": "Andrew L", "initials": "AL"}, {"family": "Rubin", "given": "Adam J", "initials": "AJ"}, {"family": "Thrane", "given": "Kim", "initials": "K"}, {"family": "Jiang", "given": "Sizun", "initials": "S"}, {"family": "Reynolds", "given": "David L", "initials": "DL"}, {"family": "Meyers", "given": "Robin M", "initials": "RM"}, {"family": "Guo", "given": "Margaret G", "initials": "MG"}, {"family": "George", "given": "Benson M", "initials": "BM"}, {"family": "Mollbrink", "given": "Annelie", "initials": "A"}, {"family": "Bergenstr\u00e5hle", "given": "Joseph", "initials": "J"}, {"family": "Larsson", "given": "Ludvig", "initials": "L"}, {"family": "Bai", "given": "Yunhao", "initials": "Y"}, {"family": "Zhu", "given": "Bokai", "initials": "B"}, {"family": "Bhaduri", "given": "Aparna", "initials": "A"}, {"family": "Meyers", "given": "Jordan M", "initials": "JM"}, {"family": "Rovira-Clav\u00e9", "given": "Xavier", "initials": "X"}, {"family": "Hollmig", "given": "S Tyler", "initials": "ST"}, {"family": "Aasi", "given": "Sumaira Z", "initials": "SZ"}, {"family": "Nolan", "given": "Garry P", "initials": "GP"}, {"family": "Lundeberg", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4313-1601", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a4e6ca0f29b4ead8569e2729481c3e0.json"}}, {"family": "Khavari", "given": "Paul A", "initials": "PA"}], "type": "journal article", "published": "2020-07-23", "journal": {"title": "Cell", "issn": "1097-4172", "volume": "182", "issue": "2", "pages": "497-514.e22", "issn-l": "0092-8674"}, "abstract": "To define the cellular composition and architecture of cutaneous squamous cell carcinoma (cSCC), we combined single-cell RNA sequencing with spatial transcriptomics and multiplexed ion beam imaging from a series of human cSCCs and matched normal skin. cSCC exhibited four tumor subpopulations, three recapitulating normal epidermal states, and a tumor-specific keratinocyte (TSK) population unique to cancer, which localized to a fibrovascular niche. Integration of single-cell and spatial data mapped ligand-receptor networks to specific cell types, revealing TSK cells as a hub for intercellular communication. Multiple features of potential immunosuppression were observed, including T regulatory cell (Treg) co-localization with CD8 T cells in compartmentalized tumor stroma. Finally, single-cell characterization of human tumor xenografts and in vivo CRISPR screens identified essential roles for specific tumor subpopulation-enriched gene networks in tumorigenesis. These data define cSCC tumor and stromal cell subpopulations, the spatial niches where they interact, and the communicating gene networks that they engage in cancer.", "doi": "10.1016/j.cell.2020.05.039", "pmid": "32579974", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service"}, "xrefs": [{"db": "pii", "key": "S0092-8674(20)30672-3"}, {"db": "pmc", "key": "PMC7391009"}], "notes": [], "created": "2020-07-08T13:03:43.753Z", "modified": "2021-11-10T12:49:04.897Z"}, {"entity": "publication", "iuid": "2630e0f636f441ac9c35de34528196eb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2630e0f636f441ac9c35de34528196eb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2630e0f636f441ac9c35de34528196eb"}}, "title": "Decellularization and recellularization of the ovary for bioengineering applications; studies in the mouse.", "authors": [{"family": "Alshaikh", "given": "Ahmed Baker", "initials": "AB"}, {"family": "Padma", "given": "Arvind Manikantan", "initials": "AM"}, {"family": "Dehlin", "given": "Matilda", "initials": "M"}, {"family": "Akouri", "given": "Randa", "initials": "R"}, {"family": "Song", "given": "Min Jong", "initials": "MJ"}, {"family": "Br\u00e4nnstr\u00f6m", "given": "Mats", "initials": "M"}, {"family": "Hellstr\u00f6m", "given": "Mats", "initials": "M", "orcid": "0000-0003-3323-5618", "researcher": {"href": "https://publications.scilifelab.se/researcher/b41c54e9336c444d9de92c43a3330c9e.json"}}], "type": "journal article", "published": "2020-07-23", "journal": {"title": "Reprod Biol Endocrinol", "issn": "1477-7827", "volume": "18", "issue": "1", "pages": "75", "issn-l": null}, "abstract": "Fertility preservation is particularly challenging in young women diagnosed with hematopoietic cancers, as transplantation of cryopreserved ovarian cortex in these women carries the risk for re-introducing cancer cells. Therefore, the construction of a bioengineered ovary that can accommodate isolated small follicles was proposed as an alternative to minimize the risk of malignancy transmission. Various options for viable bioengineered scaffolds have been reported in the literature. Previously, we reported three protocols for producing mouse ovarian scaffolds with the decellularization technique. The present study examined these scaffolds further, specifically with regards to their extracellular composition, biocompatibility and ability to support recellularization with mesenchymal stem cells.\n\nThree decellularization protocols based on 0.5% sodium dodecyl sulfate (Protocol 1; P1), or 2% sodium deoxycholate (P2), or a combination of the two detergents (P3) were applied to produce three types of scaffolds. The levels of collagen, elastin and sulfated glycosaminoglycans (sGAGs) were quantified in the remaining extracellular matrix. Detailed immunofluorescence and scanning electron microscopy imaging were conducted to assess the morphology and recellularization efficiency of the constructs after 14 days in vitro utilizing red fluorescent protein-labelled mesenchymal stem cells.\n\nAll protocols efficiently removed the DNA while the elastin content was not significantly reduced during the procedures. The SDS-protocol (P1) reduced the sGAG and the collagen content more than the SDC-protocol (P2). All scaffolds were biocompatible and recellularization was successful, particularly in several P2-derived scaffolds. The cells were extensively distributed throughout the constructs, with a denser distribution observed towards the ovarian cortex. The cell density was not significantly different (400 to 550 cells/mm2) between scaffold types. However, there was a tendency towards a higher cell density in the SDC-derived constructs. Scanning electron microscope images showed fibrous scaffolds with a dense repopulated surface structure.\n\nWhile there were differences in the key structural macromolecules between protocols, all scaffolds were biocompatible and showed effective recellularization. The results indicate that our SDC-protocol might be better than our SDS-protocol. However, additional studies are necessary to determine their suitability for attachment of small follicles and folliculogenesis.", "doi": "10.1186/s12958-020-00630-y", "pmid": "32703228", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7376865"}, {"db": "pii", "key": "10.1186/s12958-020-00630-y"}], "notes": [], "created": "2023-02-16T08:02:26.716Z", "modified": "2023-02-16T08:02:26.784Z"}, {"entity": "publication", "iuid": "e86e6226ab92413298667c47d9f2e5f1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e86e6226ab92413298667c47d9f2e5f1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e86e6226ab92413298667c47d9f2e5f1"}}, "title": "Cell-Free Protein Synthesis of Small Intrinsically Disordered Proteins for NMR Spectroscopy.", "authors": [{"family": "Isaksson", "given": "Linn\u00e9a", "initials": "L"}, {"family": "Pedersen", "given": "Anders", "initials": "A"}], "type": "journal article", "published": "2020-07-23", "journal": {"title": "Methods Mol. Biol.", "issn": "1940-6029", "volume": "2141", "issue": null, "pages": "233-245", "issn-l": "1064-3745"}, "abstract": "Cell-free protein synthesis (CFPS) is an established method to produce recombinant proteins and has been used in a wide variety of applications. The use of CFPS has almost from the onset been favorably linked to the production of isotopically labelled proteins for NMR spectroscopy as the resulting labelling of the produced protein is defined by the chosen amino acids during reaction setup. Here we describe how to set up production and isotopic labelling of small intrinsically disordered proteins (IDPs) for NMR spectroscopy applications using an E. coli-based CFPS system in batch mode.", "doi": "10.1007/978-1-0716-0524-0_11", "pmid": "32696360", "labels": {"Swedish NMR Centre": "Collaborative"}, "xrefs": [], "notes": [], "created": "2020-12-11T09:16:35.546Z", "modified": "2025-10-17T13:03:56.727Z"}, {"entity": "publication", "iuid": "de0ae51b949548c0832c9967b8f4a1a6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/de0ae51b949548c0832c9967b8f4a1a6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/de0ae51b949548c0832c9967b8f4a1a6"}}, "title": "Extended-Spectrum-\u03b2-Lactamase- and Plasmid AmpC-Producing Escherichia coli Causing Community-Onset Bloodstream Infection: Association of Bacterial Clones and Virulence Genes with Septic Shock, Source of Infection, and Recurrence.", "authors": [{"family": "Fr\u00f6ding", "given": "Inga", "initials": "I"}, {"family": "Hasan", "given": "Badrul", "initials": "B"}, {"family": "Sylvin", "given": "Isak", "initials": "I"}, {"family": "Coorens", "given": "Maarten", "initials": "M"}, {"family": "Naucl\u00e9r", "given": "Pontus", "initials": "P"}, {"family": "Giske", "given": "Christian G", "initials": "CG"}], "type": "journal article", "published": "2020-07-22", "journal": {"title": "Antimicrob. Agents Chemother.", "issn": "1098-6596", "volume": "64", "issue": "8", "issn-l": "0066-4804"}, "abstract": "Invasive infections due to extended-spectrum-\u03b2-lactamase- and pAmpC-producing Escherichia coli (ESBL/pAmpC-EC) are an important cause of morbidity, often caused by the high-risk clone sequence type (ST131) and isolates classified as extraintestinal pathogenic E. coli (ExPEC). The relative influence of host immunocompetence versus microbiological virulence factors in the acquisition and outcome of bloodstream infections (BSI) is poorly understood. Herein, we used whole-genome sequencing on 278 blood culture isolates of ESBL/pAmpC-EC from 260 patients with community-onset BSI collected from 2012 to 2015 in Stockholm to study the association of virulence genes, sequence types, and antimicrobial resistance with severity of disease, infection source, ESBL/pAmpC-EC BSI low-risk patients, and patients with repeated episodes. ST131 subclade C2 comprised 29% of all patients. Factors associated with septic shock in multivariable analysis were patient host factors (hematologic cancer or transplantation and reduced daily living activity), presence of the E. coli virulence factor iss (increased serum survival), absence of phenotypic multidrug resistance, and absence of the genes pap and hsp Adhesins, particularly pap, were associated with urinary tract infection (UTI) source, while isolates from post-prostate biopsy sepsis had a low overall number of virulence operons, including adhesins, and commonly belonged to ST131 clades A, B, and subclade C1, ST1193, and ST648. ST131 was associated with recurrent episodes. In conclusion, the most interesting finding is the association of iss with septic shock. Adhesins are important for UTI pathogenesis, while otherwise low-pathogenic isolates from the microbiota can cause post-prostate biopsy sepsis.", "doi": "10.1128/AAC.02351-19", "pmid": "32423949", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "AAC.02351-19"}, {"db": "pmc", "key": "PMC7526827"}], "notes": [], "created": "2020-06-01T09:13:35.267Z", "modified": "2021-11-10T12:50:56.968Z"}, {"entity": "publication", "iuid": "8cf987b082774293badf953bb6306328", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8cf987b082774293badf953bb6306328.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8cf987b082774293badf953bb6306328"}}, "title": "Human Immune System Variation during 1 Year.", "authors": [{"family": "Lakshmikanth", "given": "Tadepally", "initials": "T", "orcid": "0000-0001-7256-5770", "researcher": {"href": "https://publications.scilifelab.se/researcher/92e81aa6b0cf4ff0a18b14098bf0fcc1.json"}}, {"family": "Muhammad", "given": "Sayyed Auwn", "initials": "SA", "orcid": "0000-0002-6664-1607", "researcher": {"href": "https://publications.scilifelab.se/researcher/b78cfcefd650480dabe7b6473caf66f3.json"}}, {"family": "Olin", "given": "Axel", "initials": "A"}, {"family": "Chen", "given": "Yang", "initials": "Y"}, {"family": "Mikes", "given": "Jaromir", "initials": "J", "orcid": "0000-0002-9941-7855", "researcher": {"href": "https://publications.scilifelab.se/researcher/21c127bffa7c4a01af7fad8ba6bac90b.json"}}, {"family": "Fagerberg", "given": "Linn", "initials": "L", "orcid": "0000-0003-0198-7137", "researcher": {"href": "https://publications.scilifelab.se/researcher/e8db0663a10a4d9e9241457609d5952e.json"}}, {"family": "Gummesson", "given": "Anders", "initials": "A"}, {"family": "Bergstr\u00f6m", "given": "G\u00f6ran", "initials": "G"}, {"family": "Uhlen", "given": "Mathias", "initials": "M", "orcid": "0000-0002-4858-8056", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff81da3cb0cf4262873b993a1b06798c.json"}}, {"family": "Brodin", "given": "Petter", "initials": "P", "orcid": "0000-0002-8103-0046", "researcher": {"href": "https://publications.scilifelab.se/researcher/40097353cdb24e52bf2330eb687042bf.json"}}], "type": "journal article", "published": "2020-07-21", "journal": {"title": "Cell Rep", "issn": "2211-1247", "issn-l": null, "volume": "32", "issue": "3", "pages": "107923"}, "abstract": "The human immune system varies extensively between individuals, but variation within individuals over time has not been well characterized. Systems-level analyses allow for simultaneous quantification of many interacting immune system components and the inference of global regulatory principles. Here, we present a longitudinal, systems-level analysis in 99 healthy adults 50 to 65 years of age and sampled every third month for 1 year. We describe the structure of interindividual variation and characterize extreme phenotypes along a principal curve. From coordinated measurement fluctuations, we infer relationships between 115 immune cell populations and 750 plasma proteins constituting the blood immune system. While most individuals have stable immune systems, the degree of longitudinal variability is an individual feature. The most variable individuals, in the absence of overt infections, exhibited differences in markers of metabolic health suggestive of a possible link between metabolic and immunologic homeostatic regulation.", "doi": "10.1016/j.celrep.2020.107923", "pmid": "32697987", "labels": {"Affinity Proteomics Stockholm": "Service", "Cellular Immunomonitoring": "Technology development", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S2211-1247(20)30904-9"}], "notes": [], "created": "2020-07-21T20:58:52.991Z", "modified": "2024-01-16T13:48:42.124Z"}, {"entity": "publication", "iuid": "207133b880274c69ae8dd92e22f58bbe", "links": {"self": {"href": "https://publications.scilifelab.se/publication/207133b880274c69ae8dd92e22f58bbe.json"}, "display": {"href": "https://publications.scilifelab.se/publication/207133b880274c69ae8dd92e22f58bbe"}}, "title": "Descriptive Proteome Analysis to Investigate Context-Dependent Treatment Responses to OXPHOS Inhibition in Colon Carcinoma Cells Grown as Monolayer and Multicellular Tumor Spheroids.", "authors": [{"family": "Steinmetz", "given": "Julia", "initials": "J", "orcid": "0000-0001-6041-6401", "researcher": {"href": "https://publications.scilifelab.se/researcher/8beac37f4d7e4ffcb456f78e5b379c26.json"}}, {"family": "Senkowski", "given": "Wojciech", "initials": "W"}, {"family": "Lengqvist", "given": "Johan", "initials": "J"}, {"family": "Rubin", "given": "Jenny", "initials": "J"}, {"family": "Ossipova", "given": "Elena", "initials": "E"}, {"family": "Herman", "given": "Stephanie", "initials": "S"}, {"family": "Larsson", "given": "Rolf", "initials": "R"}, {"family": "Jakobsson", "given": "Per-Johan", "initials": "PJ"}, {"family": "Frykn\u00e4s", "given": "M\u00e5rten", "initials": "M"}, {"family": "Kultima", "given": "Kim", "initials": "K"}], "type": "journal article", "published": "2020-07-21", "journal": {"title": "ACS Omega", "issn": "2470-1343", "volume": "5", "issue": "28", "pages": "17242-17254", "issn-l": "2470-1343"}, "abstract": "We have previously identified selective upregulation of the mevalonate pathway genes upon inhibition of oxidative phosphorylation (OXPHOS) in quiescent cancer cells. Using mass spectrometry-based proteomics, we here investigated whether these responses are corroborated on the protein level and whether proteomics could yield unique insights into context-dependent biology. HCT116 colon carcinoma cells were cultured as monolayer cultures, proliferative multicellular tumor spheroids (P-MCTS), or quiescent (Q-MCTS) multicellular tumor spheroids and exposed to OXPHOS inhibitors: nitazoxanide, FCCP, oligomycin, and salinomycin or the HMG-CoA-reductase inhibitor simvastatin at two different doses for 6 and 24 h. Samples were processed using an in-depth bottom-up proteomics workflow resulting in a total of 9286 identified protein groups. Gene set enrichment analysis showed profound differences between the three cell systems and confirmed differential enrichment of hypoxia, OXPHOS, and cell cycle progression-related protein responses in P-MCTS and Q-MCTS. Treatment experiments showed that the observed drug-induced alterations in gene expression of metabolically challenged cells are not translated directly to the protein level, but the results reaffirmed OXPHOS as a selective vulnerability of quiescent cancer cells. This work provides rationale for the use of deep proteome profiling to identify context-dependent treatment responses and encourages further studies investigating metabolic processes that could be co-targeted together with OXPHOS to eradicate quiescent cancer cells.", "doi": "10.1021/acsomega.0c01419", "pmid": "32715210", "labels": {"Bioinformatics Support for Computational Resources": "Service", "Drug Discovery and Development": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7376893"}], "notes": [], "created": "2020-12-10T12:22:34.991Z", "modified": "2025-10-17T13:05:07.982Z"}, {"entity": "publication", "iuid": "fea1a7e762af45b685aa05c3f27307df", "links": {"self": {"href": "https://publications.scilifelab.se/publication/fea1a7e762af45b685aa05c3f27307df.json"}, "display": {"href": "https://publications.scilifelab.se/publication/fea1a7e762af45b685aa05c3f27307df"}}, "title": "Probing the retention mechanism of small hydrophilic molecules in hydrophilic interaction chromatography using saturation transfer difference nuclear magnetic resonance spectroscopy.", "authors": [{"family": "Shamshir", "given": "Adel", "initials": "A", "orcid": "0000-0002-4321-1639", "researcher": {"href": "https://publications.scilifelab.se/researcher/9593344e98f24fc48bd7efb2710e4b9f.json"}}, {"family": "Dinh", "given": "Ngoc Phuoc", "initials": "NP"}, {"family": "Jonsson", "given": "Tobias", "initials": "T"}, {"family": "Sparrman", "given": "Tobias", "initials": "T", "orcid": "0000-0002-4442-6367", "researcher": {"href": "https://publications.scilifelab.se/researcher/f0d27dbd2f014795b1f7aa164d34bada.json"}}, {"family": "Irgum", "given": "Knut", "initials": "K", "orcid": "0000-0003-3457-7564", "researcher": {"href": "https://publications.scilifelab.se/researcher/a53af6b9ed8a45748869319a088b15bf.json"}}], "type": "journal article", "published": "2020-07-19", "journal": {"title": "Journal of Chromatography A", "issn": "1873-3778", "volume": "1623", "issue": null, "pages": "461130", "issn-l": "0021-9673"}, "abstract": "The interactions and dynamic behavior of a select set of polar probe solutes have been investigated on three hydrophilic and polar commercial stationary phases using saturation transfer difference 1H nuclear magnetic resonance (STD-NMR) spectroscopy under magic angle spinning conditions. The stationary phases were equilibrated with a select set of polar solutes expected to show different interaction patterns in mixtures of deuterated acetonitrile and deuterium oxide, with ammonium acetate added to a total concentration that mimics typical eluent conditions for hydrophilic interaction chromatography (HILIC). The methylene groups of the stationary phases were selectively irradiated to saturate the ligand protons, at frequencies that minimized the overlaps with reporting protons in the test probes. During and after this radiation, the saturation rapidly spreads to all protons in the stationary phase by spin diffusion, and from those to probe protons in contact with the stationary phase. Probe protons that have been in close contact with the stationary phase and subsequently been released to the solution phase will have been more saturated due to a more efficient transfer of spin polarization by the nuclear Overhauser effect. They will therefore show a higher signal after processing of the data. Saturation transfers to protons in neutral and charged solutes could in some instances show clear orientation patterns of these solutes towards the stationary phases. The saturation profile of formamide and its N-methylated counterparts showed patterns that could be interpreted as oriented hydrogen bond interaction. From these studies, it is evident that the functional groups on the phase surface have a strong contribution to the selectivity in HILIC, and that the retention mechanism has a significant contribution from oriented interactions.", "doi": "10.1016/j.chroma.2020.461130", "pmid": "32505268", "labels": {"Swedish NMR Centre": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0021-9673(20)30359-9"}], "notes": [], "created": "2020-11-24T09:51:04.653Z", "modified": "2025-10-17T13:03:56.768Z"}, {"entity": "publication", "iuid": "27f3b4d7ee294f0a881692c618690584", "links": {"self": {"href": "https://publications.scilifelab.se/publication/27f3b4d7ee294f0a881692c618690584.json"}, "display": {"href": "https://publications.scilifelab.se/publication/27f3b4d7ee294f0a881692c618690584"}}, "title": "Validating Signal Transducer and Activator of Transcription (STAT) Protein-Inhibitor Interactions Using Biochemical and Cellular Thermal Shift Assays.", "authors": [{"family": "Attarha", "given": "Sanaz", "initials": "S"}, {"family": "Reithmeier", "given": "Anja", "initials": "A"}, {"family": "Busker", "given": "Sander", "initials": "S", "orcid": "0000-0002-7069-3864", "researcher": {"href": "https://publications.scilifelab.se/researcher/78029e78072548688bf306c577738232.json"}}, {"family": "Desroses", "given": "Matthieu", "initials": "M", "orcid": "0000-0003-4152-3855", "researcher": {"href": "https://publications.scilifelab.se/researcher/b232b70751004e9ea6b547533f901376.json"}}, {"family": "Page", "given": "Brent D G", "initials": "BDG", "orcid": "0000-0002-2101-1329", "researcher": {"href": "https://publications.scilifelab.se/researcher/87dde8251a714d26b3b7cc045b47061f.json"}}], "type": "journal article", "published": "2020-07-17", "journal": {"volume": "15", "issn": "1554-8937", "issue": "7", "pages": "1842-1851", "title": "ACS Chem. Biol.", "issn-l": "1554-8929"}, "abstract": "Signal transducer and activator of transcription (STAT) proteins have important biological functions; however, deregulation of STAT signaling is a driving force behind the onset and progression of inflammatory diseases and cancer. While their biological roles suggest that STAT proteins would be valuable targets for developing therapeutic agents, STAT proteins are notoriously difficult to inhibit using small drug-like molecules, as they do not have a distinct inhibitor binding site. Despite this, a multitude of small-molecule STAT inhibitors have been proposed, primarily focusing on inhibiting STAT3 protein to generate novel cancer therapies. Demonstrating that inhibitors bind to their targets in cells has historically been a very challenging task. With the advent of modern target engagement techniques, such as the cellular thermal shift assay (CETSA), interactions between experimental compounds and their biological targets can be detected with relative ease. To investigate interactions between STAT proteins and inhibitors, we herein developed STAT CETSAs and evaluated known STAT3 inhibitors for their ability to engage STAT proteins in biological settings. While potent binding was detected between STAT proteins and peptidic STAT inhibitors, small-molecule inhibitors elicited variable responses, most of which failed to stabilize STAT3 proteins in cells and cell lysates. The described STAT thermal stability assays represent valuable tools for evaluating proposed STAT inhibitors.", "doi": "10.1021/acschembio.0c00046", "pmid": "32412740", "labels": {"Chemical Biology Consortium Sweden": "Collaborative"}, "xrefs": [], "notes": [], "created": "2020-06-02T11:24:45.376Z", "modified": "2025-10-17T13:04:28.276Z"}, {"entity": "publication", "iuid": "8e937f3dda6749c9b966dfb4fc501d72", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8e937f3dda6749c9b966dfb4fc501d72.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8e937f3dda6749c9b966dfb4fc501d72"}}, "title": "Unveiling the activation dynamics of a fold-switch bacterial glycosyltransferase by 19F NMR.", "authors": [{"family": "Liebau", "given": "Jobst", "initials": "J", "orcid": "0000-0003-4057-6699", "researcher": {"href": "https://publications.scilifelab.se/researcher/65f4fc23bfb94c66a696b10c9469dc56.json"}}, {"family": "Tersa", "given": "Montse", "initials": "M", "orcid": "0000-0002-2370-7776", "researcher": {"href": "https://publications.scilifelab.se/researcher/cd95e469b377450980c3e9db0ce63335.json"}}, {"family": "Trastoy", "given": "Beatriz", "initials": "B"}, {"family": "Patrick", "given": "Joan", "initials": "J"}, {"family": "Rodrigo-Unzueta", "given": "Ane", "initials": "A"}, {"family": "Corzana", "given": "Francisco", "initials": "F", "orcid": "0000-0001-5597-8127", "researcher": {"href": "https://publications.scilifelab.se/researcher/ab6fbae0b56747c08573c37ef5620244.json"}}, {"family": "Sparrman", "given": "Tobias", "initials": "T", "orcid": "0000-0002-4442-6367", "researcher": {"href": "https://publications.scilifelab.se/researcher/f0d27dbd2f014795b1f7aa164d34bada.json"}}, {"family": "Guerin", "given": "Marcelo E", "initials": "ME"}, {"family": "M\u00e4ler", "given": "Lena", "initials": "L", "orcid": "0000-0002-9464-4311", "researcher": {"href": "https://publications.scilifelab.se/researcher/7bfca98ce500442788b18afe2c656c53.json"}}], "type": "journal article", "published": "2020-07-17", "journal": {"title": "J. Biol. Chem.", "issn": "1083-351X", "volume": "295", "issue": "29", "pages": "9868-9878", "issn-l": "0021-9258"}, "abstract": "Fold-switch pathways remodel the secondary structure topology of proteins in response to the cellular environment. It is a major challenge to understand the dynamics of these folding processes. Here, we conducted an in-depth analysis of the \u03b1-helix-to-\u03b2-strand and \u03b2-strand-to-\u03b1-helix transitions and domain motions displayed by the essential mannosyltransferase PimA from mycobacteria. Using 19F NMR, we identified four functionally relevant states of PimA that coexist in dynamic equilibria on millisecond-to-second timescales in solution. We discovered that fold-switching is a slow process, on the order of seconds, whereas domain motions occur simultaneously but are substantially faster, on the order of milliseconds. Strikingly, the addition of substrate accelerated the fold-switching dynamics of PimA. We propose a model in which the fold-switching dynamics constitute a mechanism for PimA activation.", "doi": "10.1074/jbc.RA120.014162", "pmid": "32434931", "labels": {"Swedish NMR Centre": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0021-9258(17)48929-0"}, {"db": "pmc", "key": "PMC7380196"}, {"db": "PDB", "key": "4NC9"}, {"db": "PDB", "key": "2GEJ"}], "notes": [], "created": "2020-11-24T20:27:10.865Z", "modified": "2025-10-17T13:03:56.779Z"}, {"entity": "publication", "iuid": "87e07ded7de44a53ae4395ae27dfc8d4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/87e07ded7de44a53ae4395ae27dfc8d4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/87e07ded7de44a53ae4395ae27dfc8d4"}}, "title": "Translating GWAS-identified loci for cardiac rhythm and rate using an in vivo image- and CRISPR/Cas9-based approach", "authors": [{"family": "von der Heyde", "given": "Benedikt", "initials": "B", "orcid": "0000-0002-9889-4027", "researcher": {"href": "https://publications.scilifelab.se/researcher/803c0e0639174a50b59ae597802e824f.json"}}, {"family": "Emmanouilidou", "given": "Anastasia", "initials": "A"}, {"family": "Mazzaferro", "given": "Eugenia", "initials": "E"}, {"family": "Vicenzi", "given": "Silvia", "initials": "S"}, {"family": "H\u00f6ijer", "given": "Ida", "initials": "I"}, {"family": "Klingstr\u00f6m", "given": "Tiffany", "initials": "T"}, {"family": "Jumaa", "given": "Sitaf", "initials": "S"}, {"family": "Dethlefsen", "given": "Olga", "initials": "O"}, {"family": "Snieder", "given": "Harold", "initials": "H", "orcid": "0000-0003-1949-2298", "researcher": {"href": "https://publications.scilifelab.se/researcher/e9276827839a4f3cb50dcaa2ad4708a5.json"}}, {"family": "de Geus", "given": "Eco", "initials": "E", "orcid": "0000-0001-6022-2666", "researcher": {"href": "https://publications.scilifelab.se/researcher/9abb01a905f347df8214d469d6c5ac45.json"}}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Ingelsson", "given": "Erik", "initials": "E", "orcid": "0000-0003-2256-6972", "researcher": {"href": "https://publications.scilifelab.se/researcher/689bc741ea6547d18de7080c84d0193e.json"}}, {"family": "Allalou", "given": "Amin", "initials": "A"}, {"family": "Brooke", "given": "Hannah L", "initials": "HL"}, {"family": "den Hoed", "given": "Marcel", "initials": "M", "orcid": "0000-0001-8081-428X", "researcher": {"href": "https://publications.scilifelab.se/researcher/d712cc087d344b15ab9a7971640acebe.json"}}], "type": "journal-article", "published": "2020-07-16", "journal": {"title": "Sci Rep", "issn": "2045-2322", "issn-l": "2045-2322", "volume": "10", "issue": "1", "pages": "11831"}, "abstract": "A meta-analysis of genome-wide association studies (GWAS) identified eight loci that are associated with heart rate variability (HRV), but candidate genes in these loci remain uncharacterized. We developed an image- and CRISPR/Cas9-based pipeline to systematically characterize candidate genes for HRV in live zebrafish embryos. Nine zebrafish orthologues of six human candidate genes were targeted simultaneously in eggs from fish that transgenically express GFP on smooth muscle cells (Tg[acta2:GFP]), to visualize the beating heart. An automated analysis of repeated 30 s recordings of beating atria in 381 live, intact zebrafish embryos at 2 and 5 days post-fertilization highlighted genes that influence HRV (hcn4 and si:dkey-65j6.2 [KIAA1755]); heart rate (rgs6 and hcn4); and the risk of sinoatrial pauses and arrests (hcn4). Exposure to 10 or 25 \u00b5M ivabradine-an open channel blocker of HCNs-for 24 h resulted in a dose-dependent higher HRV and lower heart rate at 5 days post-fertilization. Hence, our screen confirmed the role of established genes for heart rate and rhythm (RGS6 and HCN4); showed that ivabradine reduces heart rate and increases HRV in zebrafish embryos, as it does in humans; and highlighted a novel gene that plays a role in HRV (KIAA1755).", "doi": "10.1038/s41598-020-68567-1", "pmid": "32678143", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Collaborative", "BioImage Informatics": "Collaborative", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Genome Engineering Zebrafish": "Service", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC7367351"}, {"db": "pii", "key": "10.1038/s41598-020-68567-1"}], "notes": [], "created": "2020-08-19T09:27:04.550Z", "modified": "2024-01-16T13:48:42.137Z"}, {"entity": "publication", "iuid": "f261ffa0cc8d46698138b03d99cdd77a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f261ffa0cc8d46698138b03d99cdd77a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f261ffa0cc8d46698138b03d99cdd77a"}}, "title": "AML displays increased CTCF occupancy associated with aberrant gene expression and transcription factor binding.", "authors": [{"family": "Mujahed", "given": "Huthayfa", "initials": "H"}, {"family": "Miliara", "given": "Sophia", "initials": "S"}, {"family": "Neddermeyer", "given": "Anne", "initials": "A"}, {"family": "Bengtz\u00e9n", "given": "Sofia", "initials": "S"}, {"family": "Nilsson", "given": "Christer", "initials": "C"}, {"family": "Deneberg", "given": "Stefan", "initials": "S"}, {"family": "Cordeddu", "given": "Lina", "initials": "L"}, {"family": "Ekwall", "given": "Karl", "initials": "K"}, {"family": "Lennartsson", "given": "Andreas", "initials": "A"}, {"family": "Lehmann", "given": "S\u00f6ren", "initials": "S"}], "type": "journal article", "published": "2020-07-16", "journal": {"title": "Blood", "issn": "1528-0020", "volume": "136", "issue": "3", "pages": "339-352", "issn-l": "0006-4971"}, "abstract": "CCTC-binding factor (CTCF) is a key regulator of gene expression through organization of the chromatin structure. Still, it is unclear how CTCF binding is perturbed in leukemia or in cancer in general. We studied CTCF binding by chromatin immunoprecipitation sequencing in cells from patients with acute myeloid leukemia (AML) and in normal bone marrow (NBM) in the context of gene expression, DNA methylation, and azacitidine exposure. CTCF binding was increased in AML compared with NBM. Aberrant CTCF binding was enriched for motifs for key myeloid transcription factors such as CEBPA, PU.1, and RUNX1. AML with TET2 mutations was characterized by a particularly strong gain of CTCF binding, highly enriched for gain in promoter regions, while AML in general was enriched for changes at enhancers. There was a strong anticorrelation between CTCF binding and DNA methylation. Gain of CTCF occupancy was associated with increased gene expression; however, the genomic location (promoter vs distal regions) and enrichment of motifs (for repressing vs activating cofactors) were decisive for the gene expression pattern. Knockdown of CTCF in K562 cells caused loss of CTCF binding and transcriptional repression of genes with changed CTCF binding in AML, as well as loss of RUNX1 binding at RUNX1/CTCF-binding sites. In addition, CTCF knockdown caused increased differentiation. Azacitidine exposure caused major changes in CTCF occupancy in AML patient cells, partly by restoring a CTCF-binding pattern similar to NBM. We conclude that AML displays an aberrant increase in CTCF occupancy that targets key genes for AML development and impacts gene expression.", "doi": "10.1182/blood.2019002326", "pmid": "32232485", "labels": {"Bioinformatics Support, Infrastructure and Training": "Service", "Bioinformatics Support and Infrastructure": "Service", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pii", "key": "S0006-4971(20)61884-5"}], "notes": [], "created": "2021-12-02T14:26:23.756Z", "modified": "2024-01-16T13:48:42.145Z"}, {"entity": "publication", "iuid": "534eb4c366e845d48354b57133fa83a4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/534eb4c366e845d48354b57133fa83a4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/534eb4c366e845d48354b57133fa83a4"}}, "title": "RNA Splicing Alterations Induce a Cellular Stress Response Associated with Poor Prognosis in Acute Myeloid Leukemia.", "authors": [{"family": "Anande", "given": "Govardhan", "initials": "G"}, {"family": "Deshpande", "given": "Nandan P", "initials": "NP", "orcid": "0000-0002-0324-8728", "researcher": {"href": "https://publications.scilifelab.se/researcher/45367987826a4cf99bf94634b16ce616.json"}}, {"family": "Mareschal", "given": "Sylvain", "initials": "S"}, {"family": "Batcha", "given": "Aarif M N", "initials": "AMN", "orcid": "0000-0002-7972-7506", "researcher": {"href": "https://publications.scilifelab.se/researcher/a3a4ce781d524ba1a6d94fb80365b6b0.json"}}, {"family": "Hampton", "given": "Henry R", "initials": "HR"}, {"family": "Herold", "given": "Tobias", "initials": "T"}, {"family": "Lehmann", "given": "Soren", "initials": "S"}, {"family": "Wilkins", "given": "Marc R", "initials": "MR"}, {"family": "Wong", "given": "Jason W H", "initials": "JWH"}, {"family": "Unnikrishnan", "given": "Ashwin", "initials": "A", "orcid": "0000-0001-5168-8755", "researcher": {"href": "https://publications.scilifelab.se/researcher/936d5f9523d041eaadaffee5d115ce6c.json"}}, {"family": "Pimanda", "given": "John E", "initials": "JE"}], "type": "journal article", "published": "2020-07-15", "journal": {"title": "Clin. Cancer Res.", "issn": "1557-3265", "volume": "26", "issue": "14", "pages": "3597-3607", "issn-l": "1078-0432"}, "abstract": "RNA splicing is a fundamental biological process that generates protein diversity from a finite set of genes. Recurrent somatic mutations of splicing factor genes are common in some hematologic cancers but are relatively uncommon in acute myeloid leukemia (AML, < 20% of patients). We examined whether RNA splicing differences exist in AML, even in the absence of splicing factor mutations.\n\nWe developed a bioinformatics pipeline to study alternative RNA splicing in RNA-sequencing data from large cohorts of patients with AML.\n\nWe have identified recurrent differential alternative splicing between patients with poor and good prognosis. These splicing events occurred even in patients without any discernible splicing factor mutations. Alternative splicing recurrently occurred in genes with specific molecular functions, primarily related to protein translation. Developing tools to predict the functional impact of alternative splicing on the translated protein, we discovered that approximately 45% of the splicing events directly affected highly conserved protein domains. Several splicing factors were themselves misspliced and the splicing of their target transcripts were altered. Studying differential gene expression in the same patients, we identified that alternative splicing of protein translation genes in ELNAdv patients resulted in the induction of an integrated stress response and upregulation of inflammation-related genes. Finally, using machine learning techniques, we identified a splicing signature of four genes which refine the accuracy of existing risk prognosis schemes and validated it in a completely independent cohort.\n\nOur discoveries therefore identify aberrant alternative splicing as a molecular feature of adverse AML with clinical relevance.See related commentary by Bowman, p. 3503.", "doi": "10.1158/1078-0432.CCR-20-0184", "pmid": "32122925", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "1078-0432.CCR-20-0184"}], "notes": [], "created": "2023-11-27T21:58:09.939Z", "modified": "2024-01-16T13:48:42.152Z"}, {"entity": "publication", "iuid": "c554de47da4243b885a24853a0008c09", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c554de47da4243b885a24853a0008c09.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c554de47da4243b885a24853a0008c09"}}, "title": "Adding seemingly uninformative labels helps in low data regimes", "authors": [{"family": "Matsoukas", "given": "Christos", "initials": "C"}, {"family": "Hernandez", "given": "Albert", "initials": "A"}, {"family": "Liu", "given": "Yue", "initials": "Y"}, {"family": "Dembrower", "given": "Karin", "initials": "K"}, {"family": "Miranda", "given": "Gisele", "initials": "G"}, {"family": "Konuk", "given": "Emir", "initials": "E"}, {"family": "Haslum", "given": "Johan Fredin", "initials": "JF"}, {"family": "Athanasios", "given": "Nasos", "initials": "N"}, {"family": "Lindholm", "given": "Peter", "initials": "P"}, {"family": "Strand", "given": "Fredrik", "initials": "F"}, {"family": "Smith", "given": "Kevin", "initials": "K"}], "type": null, "published": "2020-07-15", "journal": {"title": "International Conference on Machine Learning (ICML)", "issn": null, "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": "Evidence suggests that networks trained on large datasets generalize well not solely because of the numerous training examples, but also class diversity which encourages learning of enriched features. This raises the question of whether this remains true when data is scarce - is there an advantage to learning with additional labels in low-data regimes? In this work, we consider a task that requires difficult-to-obtain expert annotations: tumor segmentation in mammography images. We show that, in low-data settings, performance can be improved by complementing the expert annotations with seemingly uninformative labels from non-expert annotators, turning the task into a multi-class problem. We reveal that these gains increase when less expert data is available, and uncover several interesting properties through further studies. We demonstrate our findings on CSAW-S, a new dataset that we introduce here, and confirm them on two public datasets.", "doi": "10.48550/arXiv.2008.00807", "pmid": null, "labels": {"BioImage Informatics": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [], "notes": [], "created": "2020-11-30T22:25:00.826Z", "modified": "2023-06-19T08:44:43.546Z"}, {"entity": "publication", "iuid": "15981a63f8c94a17ab3bf14f021ef2bc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/15981a63f8c94a17ab3bf14f021ef2bc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/15981a63f8c94a17ab3bf14f021ef2bc"}}, "title": "Seamless integration of image and molecular analysis for spatial transcriptomics workflows.", "authors": [{"family": "Bergenstr\u00e5hle", "given": "Joseph", "initials": "J"}, {"family": "Larsson", "given": "Ludvig", "initials": "L"}, {"family": "Lundeberg", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4313-1601", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a4e6ca0f29b4ead8569e2729481c3e0.json"}}], "type": "journal article", "published": "2020-07-14", "journal": {"title": "BMC Genomics", "issn": "1471-2164", "volume": "21", "issue": "1", "pages": "482", "issn-l": "1471-2164"}, "abstract": "Recent advancements in in situ gene expression technologies constitute a new and rapidly evolving field of transcriptomics. With the recent launch of the 10x Genomics Visium platform, such methods have started to become widely adopted. The experimental protocol is conducted on individual tissue sections collected from a larger tissue sample. The two-dimensional nature of this data requires multiple consecutive sections to be collected from the sample in order to construct a comprehensive three-dimensional map of the tissue. However, there is currently no software available that lets the user process the images, align stacked experiments, and finally visualize them together in 3D to create a holistic view of the tissue.\n\nWe have developed an R package named STUtility that takes 10x Genomics Visium data as input and provides features to perform standardized data transformations, alignment of multiple tissue sections, regional annotation, and visualizations of the combined data in a 3D model framework.\n\nSTUtility lets the user process, analyze and visualize multiple samples of spatially resolved RNA sequencing and image data from the 10x Genomics Visium platform. The package builds on the Seurat framework and uses familiar APIs and well-proven analysis methods. An introduction to the software package is available at https://ludvigla.github.io/STUtility_web_site/ .", "doi": "10.1186/s12864-020-06832-3", "pmid": "32664861", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12864-020-06832-3"}, {"db": "pmc", "key": "PMC7386244"}], "notes": [], "created": "2020-12-07T16:28:50.026Z", "modified": "2024-01-16T13:48:42.159Z"}, {"entity": "publication", "iuid": "e738969ae3c04340ac2b8599b3065498", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e738969ae3c04340ac2b8599b3065498.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e738969ae3c04340ac2b8599b3065498"}}, "title": "A Patient-Derived Cell Atlas Informs Precision Targeting of Glioblastoma.", "authors": [{"family": "Johansson", "given": "Patrik", "initials": "P"}, {"family": "Krona", "given": "Cecilia", "initials": "C"}, {"family": "Kundu", "given": "Soumi", "initials": "S"}, {"family": "Doroszko", "given": "Milena", "initials": "M"}, {"family": "Baskaran", "given": "Sathishkumar", "initials": "S"}, {"family": "Schmidt", "given": "Linn\u00e9a", "initials": "L"}, {"family": "Vinel", "given": "Claire", "initials": "C"}, {"family": "Almstedt", "given": "Elin", "initials": "E"}, {"family": "Elgendy", "given": "Ramy", "initials": "R"}, {"family": "Elfineh", "given": "Ludmila", "initials": "L"}, {"family": "Gallant", "given": "Caroline", "initials": "C"}, {"family": "Lundsten", "given": "Sara", "initials": "S"}, {"family": "Ferrer Gago", "given": "Fernando J", "initials": "FJ"}, {"family": "Hakkarainen", "given": "Aleksi", "initials": "A", "orcid": "0000-0002-7434-3431", "researcher": {"href": "https://publications.scilifelab.se/researcher/40ffa54d23d7486b86e2f7c2da49a013.json"}}, {"family": "Sipil\u00e4", "given": "Petra", "initials": "P"}, {"family": "H\u00e4ggblad", "given": "Maria", "initials": "M"}, {"family": "Martens", "given": "Ulf", "initials": "U"}, {"family": "Lundgren", "given": "Bo", "initials": "B"}, {"family": "Frigault", "given": "Melanie M", "initials": "MM"}, {"family": "Lane", "given": "David P", "initials": "DP"}, {"family": "Swartling", "given": "Fredrik J", "initials": "FJ", "orcid": "0000-0002-8460-4367", "researcher": {"href": "https://publications.scilifelab.se/researcher/69679cebbc90496f9c5b32f56d966654.json"}}, {"family": "Uhrbom", "given": "Lene", "initials": "L", "orcid": "0000-0001-8595-5698", "researcher": {"href": "https://publications.scilifelab.se/researcher/67bb8672ad514a9bb5f86c8d6b494269.json"}}, {"family": "Nestor", "given": "Marika", "initials": "M"}, {"family": "Marino", "given": "Silvia", "initials": "S"}, {"family": "Nelander", "given": "Sven", "initials": "S", "orcid": "0000-0003-1758-1262", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d684fc3b26d4741b850790ba0571c96.json"}}], "type": "journal article", "published": "2020-07-14", "journal": {"title": "Cell Rep", "issn": "2211-1247", "volume": "32", "issue": "2", "pages": "107897", "issn-l": null}, "abstract": "Glioblastoma (GBM) is a malignant brain tumor with few therapeutic options. The disease presents with a complex spectrum of genomic aberrations, but the pharmacological consequences of these aberrations are partly unknown. Here, we report an integrated pharmacogenomic analysis of 100 patient-derived GBM cell cultures from the human glioma cell culture (HGCC) cohort. Exploring 1,544 drugs, we find that GBM has two main pharmacological subgroups, marked by differential response to proteasome inhibitors and mutually exclusive aberrations in TP53 and CDKN2A/B. We confirm this trend in cell and in xenotransplantation models, and identify both Bcl-2 family inhibitors and p53 activators as potentiators of proteasome inhibitors in GBM cells. We can further predict the responses of individual cell cultures to several existing drug classes, presenting opportunities for drug repurposing and design of stratified trials. Our functionally profiled biobank provides a valuable resource for the discovery of new treatments for GBM.", "doi": "10.1016/j.celrep.2020.107897", "pmid": "32668248", "labels": {"Bioinformatics Support for Computational Resources": "Service", "Drug Discovery and Development": "Service"}, "xrefs": [{"db": "pii", "key": "S2211-1247(20)30878-0"}], "notes": [], "created": "2020-12-04T14:16:49.871Z", "modified": "2025-10-17T13:05:07.993Z"}, {"entity": "publication", "iuid": "271fb0f504db4a9a98b93b62f60dff23", "links": {"self": {"href": "https://publications.scilifelab.se/publication/271fb0f504db4a9a98b93b62f60dff23.json"}, "display": {"href": "https://publications.scilifelab.se/publication/271fb0f504db4a9a98b93b62f60dff23"}}, "title": "Mapping the Interactome of the Nuclear Heparan Sulfate Proteoglycan Syndecan-1 in Mesothelioma Cells.", "authors": [{"family": "Kumar-Singh", "given": "Ashish", "initials": "A", "orcid": "0000-0003-4403-9102", "researcher": {"href": "https://publications.scilifelab.se/researcher/825ed3faa8504b4da5261ea08c8deaa3.json"}}, {"family": "Shrinet", "given": "Jatin", "initials": "J", "orcid": "0000-0002-4274-613X", "researcher": {"href": "https://publications.scilifelab.se/researcher/63a752a87c414b78addd5bc95a2ccc42.json"}}, {"family": "Parniewska", "given": "Malgorzata Maria", "initials": "MM"}, {"family": "Fuxe", "given": "Jonas", "initials": "J"}, {"family": "Dobra", "given": "Katalin", "initials": "K"}, {"family": "Hjerpe", "given": "Anders", "initials": "A"}], "type": "journal article", "published": "2020-07-11", "journal": {"title": "Biomolecules", "issn": "2218-273X", "volume": "10", "issue": "7", "issn-l": null}, "abstract": "Syndecan-1 (SDC1) is a cell surface heparan sulfate proteoglycan (HSPG), which regulates various signaling pathways controlling the proliferation and migration of malignant mesothelioma and other types of cancer. We have previously shown that SDC1 can translocate to the nucleus in mesothelioma cells through a tubulin-dependent transport mechanism. However, the role of nuclear SDC1 is largely unknown. Here, we performed co-immunoprecipitation (Co-IP) of SDC1 in a mesothelioma cell line to identify SDC1 interacting proteins. The precipitates contained a large number of proteins, indicating the recovery of protein networks. Proteomic analysis with a focus on nuclear proteins revealed an association with pathways related to cell proliferation and RNA synthesis, splicing and transport. In support of this, the top RNA splicing candidates were verified to interact with SDC1 by Co-IP and subsequent Western blot analysis. Further loss- and gain-of-function experiments showed that SDC1 influences RNA levels in mesothelioma cells. The results identify a proteomic map of SDC1 nuclear interactors in a mesothelioma cell line and suggest a previously unknown role for SDC1 in RNA biogenesis. The results should serve as a fundament for further studies to discover the role of nuclear SDC1 in normal and cancer cells of different origin.", "doi": "10.3390/biom10071034", "pmid": "32664515", "labels": {"Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pii", "key": "biom10071034"}, {"db": "pmc", "key": "PMC7408266"}], "notes": [], "created": "2022-03-29T11:59:16.891Z", "modified": "2022-03-29T11:59:17.029Z"}, {"entity": "publication", "iuid": "eb85d8ec7f9746d88a03ac6981ab0223", "links": {"self": {"href": "https://publications.scilifelab.se/publication/eb85d8ec7f9746d88a03ac6981ab0223.json"}, "display": {"href": "https://publications.scilifelab.se/publication/eb85d8ec7f9746d88a03ac6981ab0223"}}, "title": "Transcriptional responses in Parascaris univalens after in vitro exposure to ivermectin, pyrantel citrate and thiabendazole.", "authors": [{"family": "Martin", "given": "Frida", "initials": "F", "orcid": "0000-0002-3149-3835", "researcher": {"href": "https://publications.scilifelab.se/researcher/eacd9c056fb1451994bf6ab3289bbeb1.json"}}, {"family": "Dube", "given": "Faruk", "initials": "F"}, {"family": "Karlsson Lindsj\u00f6", "given": "Oskar", "initials": "O"}, {"family": "Eydal", "given": "Matth\u00edas", "initials": "M"}, {"family": "H\u00f6glund", "given": "Johan", "initials": "J"}, {"family": "Bergstr\u00f6m", "given": "Tomas F", "initials": "TF"}, {"family": "Tyd\u00e9n", "given": "Eva", "initials": "E"}], "type": "journal article", "published": "2020-07-09", "journal": {"title": "Parasit Vectors", "issn": "1756-3305", "volume": "13", "issue": "1", "pages": "342", "issn-l": "1756-3305"}, "abstract": "Parascaris univalens is a pathogenic parasite of foals and yearlings worldwide. In recent years, Parascaris spp. worms have developed resistance to several of the commonly used anthelmintics, though currently the mechanisms behind this development are unknown. The aim of this study was to investigate the transcriptional responses in adult P. univalens worms after in vitro exposure to different concentrations of three anthelmintic drugs, focusing on drug targets and drug metabolising pathways.\n\nAdult worms were collected from the intestines of two foals at slaughter. The foals were naturally infected and had never been treated with anthelmintics. Worms were incubated in cell culture media containing different concentrations of either ivermectin (10-9 M, 10-11 M, 10-13 M), pyrantel citrate (10-6 M, 10-8 M, 10-10 M), thiabendazole (10-5 M, 10-7 M, 10-9 M) or without anthelmintics (control) at 37 \u00b0C for 24 h. After incubation, the viability of the worms was assessed and RNA extracted from the anterior region of 36 worms and sequenced on an Illumina NovaSeq 6000 system.\n\nAll worms were alive at the end of the incubation but showed varying degrees of viability depending on the drug and concentration used. Differential expression (Padj < 0.05 and log2 fold change \u2265 1 or \u2264 - 1) analysis showed similarities and differences in the transcriptional response after exposure to the different drug classes. Candidate genes upregulated or downregulated in drug exposed worms include members of the phase I metabolic pathway short-chain dehydrogenase/reductase superfamily (SDR), flavin containing monooxygenase superfamily (FMO) and cytochrome P450-family (CYP), as well as members of the membrane transporters major facilitator superfamily (MFS) and solute carrier superfamily (SLC). Generally, different targets of the anthelmintics used were found to be upregulated and downregulated in an unspecific pattern after drug exposure, apart from the GABA receptor subunit lgc-37, which was upregulated only in worms exposed to 10-9 M of ivermectin.\n\nTo our knowledge, this is the first time the expression of lgc-37 and members of the FMO, SDR, MFS and SLC superfamilies have been described in P. univalens and future work should be focused on characterising these candidate genes to further explore their potential involvement in drug metabolism and anthelmintic resistance.", "doi": "10.1186/s13071-020-04212-0", "pmid": "32646465", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s13071-020-04212-0"}, {"db": "pmc", "key": "PMC7346371"}], "notes": [], "created": "2020-12-08T23:34:23.929Z", "modified": "2024-01-16T13:48:42.174Z"}, {"entity": "publication", "iuid": "d7e8b72bb7424ac1a101bd09cdf9cc30", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d7e8b72bb7424ac1a101bd09cdf9cc30.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d7e8b72bb7424ac1a101bd09cdf9cc30"}}, "title": "SF3B1-mutant MDS as a distinct disease subtype: a proposal from the International Working Group for the Prognosis of MDS.", "authors": [{"family": "Malcovati", "given": "Luca", "initials": "L"}, {"family": "Stevenson", "given": "Kristen", "initials": "K"}, {"family": "Papaemmanuil", "given": "Elli", "initials": "E"}, {"family": "Neuberg", "given": "Donna", "initials": "D"}, {"family": "Bejar", "given": "Rafael", "initials": "R", "orcid": "0000-0002-5603-4598", "researcher": {"href": "https://publications.scilifelab.se/researcher/33fcd878bc6e48e98950a35a0cebdbbb.json"}}, {"family": "Boultwood", "given": "Jacqueline", "initials": "J", "orcid": "0000-0002-4330-2928", "researcher": {"href": "https://publications.scilifelab.se/researcher/389b184fad7048daaa8bd0466b298374.json"}}, {"family": "Bowen", "given": "David T", "initials": "DT"}, {"family": "Campbell", "given": "Peter J", "initials": "PJ"}, {"family": "Ebert", "given": "Benjamin L", "initials": "BL"}, {"family": "Fenaux", "given": "Pierre", "initials": "P"}, {"family": "Haferlach", "given": "Torsten", "initials": "T"}, {"family": "Heuser", "given": "Michael", "initials": "M"}, {"family": "Jansen", "given": "Joop H", "initials": "JH"}, {"family": "Komrokji", "given": "Rami S", "initials": "RS"}, {"family": "Maciejewski", "given": "Jaroslaw P", "initials": "JP"}, {"family": "Walter", "given": "Matthew J", "initials": "MJ"}, {"family": "Fontenay", "given": "Michaela", "initials": "M"}, {"family": "Garcia-Manero", "given": "Guillermo", "initials": "G"}, {"family": "Graubert", "given": "Timothy A", "initials": "TA"}, {"family": "Karsan", "given": "Aly", "initials": "A"}, {"family": "Meggendorfer", "given": "Manja", "initials": "M"}, {"family": "Pellagatti", "given": "Andrea", "initials": "A"}, {"family": "Sallman", "given": "David A", "initials": "DA"}, {"family": "Savona", "given": "Michael R", "initials": "MR", "orcid": "0000-0003-3763-5504", "researcher": {"href": "https://publications.scilifelab.se/researcher/50a3df7d0cee4ad484ba249dc87de866.json"}}, {"family": "Sekeres", "given": "Mikkael A", "initials": "MA"}, {"family": "Steensma", "given": "David P", "initials": "DP", "orcid": "0000-0001-5130-9284", "researcher": {"href": "https://publications.scilifelab.se/researcher/5dbccbde21fc4819b45583d5ecefc3e6.json"}}, {"family": "Tauro", "given": "Sudhir", "initials": "S", "orcid": "0000-0002-7236-970X", "researcher": {"href": "https://publications.scilifelab.se/researcher/311f863e8ab747468fafc068f4d1d297.json"}}, {"family": "Thol", "given": "Felicitas", "initials": "F"}, {"family": "Vyas", "given": "Paresh", "initials": "P", "orcid": "0000-0003-3931-0914", "researcher": {"href": "https://publications.scilifelab.se/researcher/dbe356d5bf3e4965a2e82c4c0bb32ed8.json"}}, {"family": "Van de Loosdrecht", "given": "Arjan A", "initials": "AA"}, {"family": "Haase", "given": "Detlef", "initials": "D"}, {"family": "T\u00fcchler", "given": "Heinz", "initials": "H"}, {"family": "Greenberg", "given": "Peter L", "initials": "PL"}, {"family": "Ogawa", "given": "Seishi", "initials": "S", "orcid": "0000-0002-7778-5374", "researcher": {"href": "https://publications.scilifelab.se/researcher/fbcc3b1b5f3045a7acd123222445449d.json"}}, {"family": "Hellstrom-Lindberg", "given": "Eva", "initials": "E"}, {"family": "Cazzola", "given": "Mario", "initials": "M"}], "type": "journal article", "published": "2020-07-09", "journal": {"title": "Blood", "issn": "1528-0020", "volume": "136", "issue": "2", "pages": "157-170", "issn-l": "0006-4971"}, "abstract": "The 2016 revision of the World Health Organization classification of tumors of hematopoietic and lymphoid tissues is characterized by a closer integration of morphology and molecular genetics. Notwithstanding, the myelodysplastic syndrome (MDS) with isolated del(5q) remains so far the only MDS subtype defined by a genetic abnormality. Approximately half of MDS patients carry somatic mutations in spliceosome genes, with SF3B1 being the most commonly mutated one. SF3B1 mutation identifies a condition characterized by ring sideroblasts (RS), ineffective erythropoiesis, and indolent clinical course. A large body of evidence supports recognition of SF3B1-mutant MDS as a distinct nosologic entity. To further validate this notion, we interrogated the data set of the International Working Group for the Prognosis of MDS (IWG-PM). Based on the findings of our analyses, we propose the following diagnostic criteria for SF3B1-mutant MDS: (1) cytopenia as defined by standard hematologic values, (2) somatic SF3B1 mutation, (3) morphologic dysplasia (with or without RS), and (4) bone marrow blasts <5% and peripheral blood blasts <1%. Selected concomitant genetic lesions represent exclusion criteria for the proposed entity. In patients with clonal cytopenia of undetermined significance, SF3B1 mutation is almost invariably associated with subsequent development of overt MDS with RS, suggesting that this genetic lesion might provide presumptive evidence of MDS in the setting of persistent unexplained cytopenia. Diagnosis of SF3B1-mutant MDS has considerable clinical implications in terms of risk stratification and therapeutic decision making. In fact, this condition has a relatively good prognosis and may respond to luspatercept with abolishment of the transfusion requirement.", "doi": "10.1182/blood.2020004850", "pmid": "32347921", "labels": {"Clinical Genomics Uppsala": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "S0006-4971(20)61895-X"}, {"db": "pmc", "key": "PMC7362582"}], "notes": [], "created": "2020-12-10T14:46:51.952Z", "modified": "2021-11-10T12:49:21.516Z"}, {"entity": "publication", "iuid": "9415049166944ab6990231e492323800", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9415049166944ab6990231e492323800.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9415049166944ab6990231e492323800"}}, "title": "Disturbance history can increase functional stability in the face of both repeated disturbances of the same type and novel disturbances.", "authors": [{"family": "Renes", "given": "Sophia Elise", "initials": "SE"}, {"family": "Sj\u00f6stedt", "given": "Johanna", "initials": "J"}, {"family": "Fetzer", "given": "Ingo", "initials": "I"}, {"family": "Langenheder", "given": "Silke", "initials": "S"}], "type": "journal article", "published": "2020-07-09", "journal": {"title": "Sci Rep", "issn": "2045-2322", "issn-l": "2045-2322", "volume": "10", "issue": "1", "pages": "11333"}, "abstract": "Climate change is expected to increase the incidences of extremes in environmental conditions. To investigate how repeated disturbances affect microbial ecosystem resistance, natural lake bacterioplankton communities were subjected to repeated temperature disturbances of two intensities (25 \u00b0C and 35 \u00b0C), and subsequently to an acidification event. We measured functional parameters (bacterial production, abundance, extracellular enzyme activities) and community composition parameters (richness, evenness, niche width) and found that, compared to undisturbed control communities, the 35 \u00b0C treatment was strongly affected in all parameters, while the 25 \u00b0C treatment did not significantly differ from the control. Interestingly, exposure to multiple temperature disturbances caused gradually increasing stability in the 35 \u00b0C treatment in some parameters, while others parameters showed the opposite, indicating that the choice of parameters can strongly affect the outcome of a study. The acidification event did not lead to stronger changes in community structure, but functional resistance of bacterial production towards acidification in the 35 \u00b0C treatments increased. This indicates that functional resistance in response to a novel disturbance can be increased by previous exposure to another disturbance, suggesting similarity in stress tolerance mechanisms for both disturbances. These results highlight the need for understanding function- and disturbance-specific responses, since general responses are likely to be unpredictable.", "doi": "10.1038/s41598-020-68104-0", "pmid": "32647292", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-68104-0"}, {"db": "pmc", "key": "PMC7347917"}], "notes": [], "created": "2020-12-08T23:18:02.286Z", "modified": "2024-01-16T13:48:42.181Z"}, {"entity": "publication", "iuid": "e76e376e1c7c41c0a688e1d45b66a687", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e76e376e1c7c41c0a688e1d45b66a687.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e76e376e1c7c41c0a688e1d45b66a687"}}, "title": "Arachidonic acid promotes the binding of 5-lipoxygenase on nanodiscs containing 5-lipoxygenase activating protein in the absence of calcium-ions.", "authors": [{"family": "Kumar", "given": "Ramakrishnan B", "initials": "RB"}, {"family": "Purhonen", "given": "Pasi", "initials": "P"}, {"family": "Hebert", "given": "Hans", "initials": "H"}, {"family": "Jegersch\u00f6ld", "given": "Caroline", "initials": "C", "orcid": "0000-0003-2419-6354", "researcher": {"href": "https://publications.scilifelab.se/researcher/8347d1cd23e34296959985176a689b42.json"}}], "type": "journal article", "published": "2020-07-09", "journal": {"title": "PLoS ONE", "issn": "1932-6203", "volume": "15", "issue": "7", "pages": "e0228607", "issn-l": "1932-6203"}, "abstract": "Among the first steps in inflammation is the conversion of arachidonic acid (AA) stored in the cell membranes into leukotrienes. This occurs mainly in leukocytes and depends on the interaction of two proteins: 5-lipoxygenase (5LO), stored away from the nuclear membranes until use and 5-lipoxygenase activating protein (FLAP), a transmembrane, homotrimeric protein, constitutively present in nuclear membrane. We could earlier visualize the binding of 5LO to nanodiscs in the presence of Ca2+-ions by the use of transmission electron microscopy (TEM) on samples negatively stained by sodium phosphotungstate. In the absence of Ca2+-ions 5LO did not bind to the membrane. In the present communication, FLAP reconstituted in the nanodiscs which could be purified if the His-tag was located on the FLAP C-terminus but not the N-terminus. Our aim was to find out if 1) 5LO would bind in a Ca2+-dependent manner also when FLAP is present? 2) Would the substrate (AA) have effects on 5LO binding to FLAP-nanodiscs? TEM was used to assess the complex formation between 5LO and FLAP-nanodiscs along with, sucrose gradient purification, gel-electrophoresis and mass spectrometry. It was found that presence of AA by itself induces complex formation in the absence of added calcium. This finding corroborates that AA is necessary for the complex formation and that a Ca2+-flush is mainly needed for the recruitment of 5LO to the membrane. Our results also showed that the addition of Ca2+-ions promoted binding of 5LO on the FLAP-nanodiscs as was also the case for nanodiscs without FLAP incorporated. In the absence of added substances no 5LO-FLAP complex was formed. Another finding is that the formation of a 5LO-FLAP complex appears to induce fragmentation of 5LO in vitro.", "doi": "10.1371/journal.pone.0228607", "pmid": "32645009", "labels": {"Protein Science Facility (PSF)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7347166"}, {"db": "pii", "key": "PONE-D-20-01617"}], "notes": [], "created": "2024-04-03T14:20:58.416Z", "modified": "2024-04-03T14:20:58.550Z"}, {"entity": "publication", "iuid": "92f8202f59a04becbbbcac6a1abbc60d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/92f8202f59a04becbbbcac6a1abbc60d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/92f8202f59a04becbbbcac6a1abbc60d"}}, "title": "Systems biology of acidophile biofilms for efficient metal extraction.", "authors": [{"family": "Buetti-Dinh", "given": "Antoine", "initials": "A"}, {"family": "Herold", "given": "Malte", "initials": "M"}, {"family": "Christel", "given": "Stephan", "initials": "S"}, {"family": "Hajjami", "given": "Mohamed El", "initials": "ME"}, {"family": "Bellenberg", "given": "S\u00f6ren", "initials": "S"}, {"family": "Ilie", "given": "Olga", "initials": "O"}, {"family": "Wilmes", "given": "Paul", "initials": "P"}, {"family": "Poetsch", "given": "Ansgar", "initials": "A"}, {"family": "Sand", "given": "Wolfgang", "initials": "W"}, {"family": "Vera", "given": "Mario", "initials": "M"}, {"family": "Pivkin", "given": "Igor V", "initials": "IV"}, {"family": "Dopson", "given": "Mark", "initials": "M", "orcid": "0000-0002-9622-3318", "researcher": {"href": "https://publications.scilifelab.se/researcher/1dc9cc6dadf6483e88d855dc78709a59.json"}}], "type": "dataset", "published": "2020-07-07", "journal": {"title": "Sci Data", "issn": "2052-4463", "volume": "7", "issue": "1", "pages": "215", "issn-l": "2052-4463"}, "abstract": "Society's demand for metals is ever increasing while stocks of high-grade minerals are being depleted. Biomining, for example of chalcopyrite for copper recovery, is a more sustainable biotechnological process that exploits the capacity of acidophilic microbes to catalyze solid metal sulfide dissolution to soluble metal sulfates. A key early stage in biomining is cell attachment and biofilm formation on the mineral surface that results in elevated mineral oxidation rates. Industrial biomining of chalcopyrite is typically carried out in large scale heaps that suffer from the downsides of slow and poor metal recoveries. In an effort to mitigate these drawbacks, this study investigated planktonic and biofilm cells of acidophilic (optimal growth pH < 3) biomining bacteria. RNA and proteins were extracted, and high throughput \"omics\" performed from a total of 80 biomining experiments. In addition, micrographs of biofilm formation on the chalcopyrite mineral surface over time were generated from eight separate experiments. The dataset generated in this project will be of great use to microbiologists, biotechnologists, and industrial researchers.", "doi": "10.1038/s41597-020-0519-2", "pmid": "32636389", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41597-020-0519-2"}, {"db": "pmc", "key": "PMC7340779"}], "notes": [], "created": "2020-12-07T16:29:57.828Z", "modified": "2024-01-16T13:48:42.188Z"}, {"entity": "publication", "iuid": "110fc8367dec489db814cf5a89464741", "links": {"self": {"href": "https://publications.scilifelab.se/publication/110fc8367dec489db814cf5a89464741.json"}, "display": {"href": "https://publications.scilifelab.se/publication/110fc8367dec489db814cf5a89464741"}}, "title": "Low Abundance of Methanotrophs in Sediments of Shallow Boreal Coastal Zones With High Water Methane Concentrations.", "authors": [{"family": "Broman", "given": "Elias", "initials": "E"}, {"family": "Sun", "given": "Xiaole", "initials": "X"}, {"family": "Stranne", "given": "Christian", "initials": "C"}, {"family": "Salgado", "given": "Marco G", "initials": "MG"}, {"family": "Bonaglia", "given": "Stefano", "initials": "S"}, {"family": "Geibel", "given": "Marc", "initials": "M"}, {"family": "Jakobsson", "given": "Martin", "initials": "M"}, {"family": "Norkko", "given": "Alf", "initials": "A"}, {"family": "Humborg", "given": "Christoph", "initials": "C"}, {"family": "Nascimento", "given": "Francisco J A", "initials": "FJA"}], "type": "journal article", "published": "2020-07-07", "journal": {"title": "Front Microbiol", "issn": "1664-302X", "volume": "11", "issue": null, "pages": "1536", "issn-l": "1664-302X"}, "abstract": "Coastal zones are transitional areas between land and sea where large amounts of organic and inorganic carbon compounds are recycled by microbes. Especially shallow zones near land have been shown to be the main source for oceanic methane (CH4) emissions. Water depth has been predicted as the best explanatory variable, which is related to CH4 ebullition, but exactly how sediment methanotrophs mediates these emissions along water depth is unknown. Here, we investigated the relative abundance and RNA transcripts attributed to methane oxidation proteins of aerobic methanotrophs in the sediment of shallow coastal zones with high CH4 concentrations within a depth gradient from 10-45 m. Field sampling consisted of collecting sediment (top 0-2 cm layer) from eight stations along this depth gradient in the coastal Baltic Sea. The relative abundance and RNA transcripts attributed to the CH4 oxidizing protein (pMMO; particulate methane monooxygenase) of the dominant methanotroph Methylococcales was significantly higher in deeper costal offshore areas (36-45 m water depth) compared to adjacent shallow zones (10-28 m). This was in accordance with the shallow zones having higher CH4 concentrations in the surface water, as well as more CH4 seeps from the sediment. Furthermore, our findings indicate that the low prevalence of Methylococcales and RNA transcripts attributed to pMMO was restrained to the euphotic zone (indicated by Photosynthetically active radiation (PAR) data, photosynthesis proteins, and 18S rRNA data of benthic diatoms). This was also indicated by a positive relationship between water depth and the relative abundance of Methylococcales and pMMO. How these processes are affected by light availability requires further studies. CH4 ebullition potentially bypasses aerobic methanotrophs in shallow coastal areas, reducing CH4 availability and limiting their growth. Such mechanism could help explain their reduced relative abundance and related RNA transcripts for pMMO. These findings can partly explain the difference in CH4 concentrations between shallow and deep coastal areas, and the relationship between CH4 concentrations and water depth.", "doi": "10.3389/fmicb.2020.01536", "pmid": "32733420", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7362727"}], "notes": [], "created": "2020-12-07T16:32:26.232Z", "modified": "2024-01-16T13:48:42.195Z"}, {"entity": "publication", "iuid": "c7e200350fda45a291ec77006ecc5bbb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c7e200350fda45a291ec77006ecc5bbb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c7e200350fda45a291ec77006ecc5bbb"}}, "title": "Discovery and population genomics of structural variation in a songbird genus.", "authors": [{"family": "Weissensteiner", "given": "Matthias H", "initials": "MH", "orcid": "0000-0001-9302-798X", "researcher": {"href": "https://publications.scilifelab.se/researcher/5550a93e906d4e25985cd7641f8be554.json"}}, {"family": "Bunikis", "given": "Ignas", "initials": "I"}, {"family": "Catal\u00e1n", "given": "Ana", "initials": "A"}, {"family": "Francoijs", "given": "Kees-Jan", "initials": "KJ"}, {"family": "Knief", "given": "Ulrich", "initials": "U", "orcid": "0000-0001-6959-3033", "researcher": {"href": "https://publications.scilifelab.se/researcher/5d8858c7c7b44a008a172bc637957ce1.json"}}, {"family": "Heim", "given": "Wieland", "initials": "W", "orcid": "0000-0002-3262-2491", "researcher": {"href": "https://publications.scilifelab.se/researcher/a88dd35e7b8a46b49c9e2ccc6d712b45.json"}}, {"family": "Peona", "given": "Valentina", "initials": "V", "orcid": "0000-0001-5119-1837", "researcher": {"href": "https://publications.scilifelab.se/researcher/d4903a935025452f88e4f1c02483829b.json"}}, {"family": "Pophaly", "given": "Saurabh D", "initials": "SD"}, {"family": "Sedlazeck", "given": "Fritz J", "initials": "FJ"}, {"family": "Suh", "given": "Alexander", "initials": "A", "orcid": "0000-0002-8979-9992", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e39e1313d894596a6c4ed949e43e019.json"}}, {"family": "Warmuth", "given": "Vera M", "initials": "VM"}, {"family": "Wolf", "given": "Jochen B W", "initials": "JBW"}], "type": "journal article", "published": "2020-07-07", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "11", "issue": "1", "pages": "3403"}, "abstract": "Structural variation (SV) constitutes an important type of genetic mutations providing the raw material for evolution. Here, we uncover the genome-wide spectrum of intra- and interspecific SV segregating in natural populations of seven songbird species in the genus Corvus. Combining short-read (N = 127) and long-read re-sequencing (N = 31), as well as optical mapping (N = 16), we apply both assembly- and read mapping approaches to detect SV and characterize a total of 220,452 insertions, deletions and inversions. We exploit sampling across wide phylogenetic timescales to validate SV genotypes and assess the contribution of SV to evolutionary processes in an avian model of incipient speciation. We reveal an evolutionary young (~530,000 years) cis-acting 2.25-kb LTR retrotransposon insertion reducing expression of the NDP gene with consequences for premating isolation. Our results attest to the wealth and evolutionary significance of SV segregating in natural populations and highlight the need for reliable SV genotyping.", "doi": "10.1038/s41467-020-17195-4", "pmid": "32636372", "labels": {"National Genomics Infrastructure": "Collaborative", "NGI Uppsala (Uppsala Genome Center)": "Collaborative", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-17195-4"}, {"db": "pmc", "key": "PMC7341801"}, {"db": "Dryad", "key": "10.5061/dryad.ns1rn8ppj"}], "notes": [], "created": "2020-08-25T12:55:18.199Z", "modified": "2024-01-16T13:48:42.202Z"}, {"entity": "publication", "iuid": "90da40e1f7324fa4a32dc842a59eb5aa", "links": {"self": {"href": "https://publications.scilifelab.se/publication/90da40e1f7324fa4a32dc842a59eb5aa.json"}, "display": {"href": "https://publications.scilifelab.se/publication/90da40e1f7324fa4a32dc842a59eb5aa"}}, "title": "Clonal hematopoiesis in patients with high-grade B-cell lymphoma is associated with inferior outcome.", "authors": [{"family": "Amini", "given": "Rose-Marie", "initials": "RM", "orcid": "0000-0003-0901-5252", "researcher": {"href": "https://publications.scilifelab.se/researcher/c157abcd61fa4900b5ad502b408d6d95.json"}}, {"family": "Ljungstr\u00f6m", "given": "Viktor", "initials": "V"}, {"family": "Abdulla", "given": "Maysaa", "initials": "M", "orcid": "0000-0002-0766-0656", "researcher": {"href": "https://publications.scilifelab.se/researcher/7aa1427f158d44448862d0f1f28723b2.json"}}, {"family": "Cavelier", "given": "Lucia", "initials": "L", "orcid": "0009-0003-8195-370X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f01226edb140436da0c9d166c1f5fe51.json"}}, {"family": "Pandzic", "given": "Tatjana", "initials": "T"}, {"family": "Hollander", "given": "Peter", "initials": "P", "orcid": "0000-0002-0226-5681", "researcher": {"href": "https://publications.scilifelab.se/researcher/b1c6693d3ede463eb78e6da010db601f.json"}}, {"family": "Enblad", "given": "Gunilla", "initials": "G"}, {"family": "Baliakas", "given": "Panagiotis", "initials": "P", "orcid": "0000-0002-5634-7156", "researcher": {"href": "https://publications.scilifelab.se/researcher/17370bd509dc4b1081af5aed9e5117c7.json"}}], "type": "letter", "published": "2020-07-06", "journal": {"title": "Am. J. Hematol.", "issn": "1096-8652", "volume": "95", "issue": "10", "pages": null, "issn-l": "0361-8609"}, "abstract": null, "doi": "10.1002/ajh.25927", "pmid": "32628289", "labels": {"Clinical Genomics Uppsala": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [], "notes": [], "created": "2020-11-06T13:03:32.457Z", "modified": "2021-11-10T12:49:27.847Z"}, {"entity": "publication", "iuid": "14f75a9338b14c19b1465b9d5f897d0b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/14f75a9338b14c19b1465b9d5f897d0b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/14f75a9338b14c19b1465b9d5f897d0b"}}, "title": "VEGF-B signaling impairs endothelial glucose transcytosis by decreasing membrane cholesterol content.", "authors": [{"family": "Moessinger", "given": "Christine", "initials": "C"}, {"family": "Nilsson", "given": "Ingrid", "initials": "I"}, {"family": "Muhl", "given": "Lars", "initials": "L"}, {"family": "Zeitelhofer", "given": "Manuel", "initials": "M"}, {"family": "Heller Sahlgren", "given": "Benjamin", "initials": "B"}, {"family": "Skogsberg", "given": "Josefin", "initials": "J"}, {"family": "Eriksson", "given": "Ulf", "initials": "U", "orcid": "0000-0002-4439-3980", "researcher": {"href": "https://publications.scilifelab.se/researcher/635596fee21941a6b444926375d19cd0.json"}}], "type": "journal article", "published": "2020-07-03", "journal": {"title": "EMBO Rep.", "issn": "1469-3178", "volume": "21", "issue": "7", "pages": "e49343", "issn-l": "1469-221X"}, "abstract": "Regulation of endothelial nutrient transport is poorly understood. Vascular endothelial growth factor B (VEGF-B) signaling in endothelial cells promotes uptake and transcytosis of fatty acids from the bloodstream to the underlying tissue, advancing pathological lipid accumulation and lipotoxicity in diabetic complications. Here, we demonstrate that VEGF-B limits endothelial glucose transport independent of fatty acid uptake. Specifically, VEGF-B signaling impairs recycling of low-density lipoprotein receptor (LDLR) to the plasma membrane, leading to reduced cholesterol uptake and membrane cholesterol loading. Reduced cholesterol levels in the membrane leads to a decrease in glucose transporter 1 (GLUT1)-dependent endothelial glucose uptake. Inhibiting VEGF-B in vivo reconstitutes membrane cholesterol levels and restores glucose uptake, which is of particular relevance for conditions involving insulin resistance and diabetic complications. In summary, our study reveals a mechanism whereby VEGF-B regulates endothelial nutrient uptake and highlights the impact of membrane cholesterol for regulation of endothelial glucose transport.", "doi": "10.15252/embr.201949343", "pmid": "32449307", "labels": {"Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7332976"}, {"db": "GEO", "key": "GSE146109"}], "notes": [], "created": "2020-12-11T12:04:53.020Z", "modified": "2025-10-17T13:03:16.721Z"}, {"entity": "publication", "iuid": "5d10760287d3464a96f10a51a55e9a7c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5d10760287d3464a96f10a51a55e9a7c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5d10760287d3464a96f10a51a55e9a7c"}}, "title": "Spatio-molecular domains identified in the mouse subthalamic nucleus and neighboring glutamatergic and GABAergic brain structures.", "authors": [{"family": "Wall\u00e9n-Mackenzie", "given": "\u00c5sa", "initials": "\u00c5", "orcid": "0000-0002-8713-070X", "researcher": {"href": "https://publications.scilifelab.se/researcher/eeda951c090846008ee77d1aa28e5fe1.json"}}, {"family": "Dumas", "given": "Sylvie", "initials": "S", "orcid": "0000-0002-4415-9924", "researcher": {"href": "https://publications.scilifelab.se/researcher/0393bec924d24ecfaa75cd77062b7231.json"}}, {"family": "Papathanou", "given": "Maria", "initials": "M", "orcid": "0000-0002-0845-9831", "researcher": {"href": "https://publications.scilifelab.se/researcher/281c8a847ca64d50988627c9d92f5b8a.json"}}, {"family": "Martis Thiele", "given": "Mihaela M", "initials": "MM"}, {"family": "Vlcek", "given": "Bianca", "initials": "B", "orcid": "0000-0001-5442-2303", "researcher": {"href": "https://publications.scilifelab.se/researcher/7afc70325f904d95b16a5e0fc9179e4b.json"}}, {"family": "K\u00f6nig", "given": "Niclas", "initials": "N", "orcid": "0000-0003-0899-046X", "researcher": {"href": "https://publications.scilifelab.se/researcher/7def2d96c45b462fa50a6579ad1dad97.json"}}, {"family": "Bj\u00f6rklund", "given": "\u00c5sa K", "initials": "\u00c5K", "orcid": "0000-0003-2224-7090", "researcher": {"href": "https://publications.scilifelab.se/researcher/8eb8c1fc5f704cbfb87471226485ae1f.json"}}], "type": "journal article", "published": "2020-07-03", "journal": {"title": "Commun Biol", "issn": "2399-3642", "issn-l": "2399-3642", "volume": "3", "issue": "1", "pages": "338"}, "abstract": "The subthalamic nucleus (STN) is crucial for normal motor, limbic and associative function. STN dysregulation is correlated with several brain disorders, including Parkinson's disease and obsessive compulsive disorder (OCD), for which high-frequency stimulation of the STN is increasing as therapy. However, clinical progress is hampered by poor knowledge of the anatomical-functional organization of the STN. Today, experimental mouse genetics provides outstanding capacity for functional decoding, provided selective promoters are available. Here, we implemented single-nuclei RNA sequencing (snRNASeq) of the mouse STN followed through with histological analysis of 16 candidate genes of interest. Our results demonstrate that the mouse STN is composed of at least four spatio-molecularly defined domains, each distinguished by defined sets of promoter activities. Further, molecular profiles dissociate the STN from the adjoining para-STN (PSTN) and neighboring structures of the hypothalamus, mammillary nuclei and zona incerta. Enhanced knowledge of STN\u00b4s internal organization should prove useful towards genetics-based functional decoding of this clinically relevant brain structure.", "doi": "10.1038/s42003-020-1028-8", "pmid": "32620779", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Eukaryotic Single Cell Genomics (ESCG)": "Service", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s42003-020-1028-8"}, {"db": "pmc", "key": "PMC7334224"}], "notes": [], "created": "2020-08-10T12:44:57.714Z", "modified": "2024-01-16T13:48:42.209Z"}, {"entity": "publication", "iuid": "011596f9427341e9be5a619b81b0b796", "links": {"self": {"href": "https://publications.scilifelab.se/publication/011596f9427341e9be5a619b81b0b796.json"}, "display": {"href": "https://publications.scilifelab.se/publication/011596f9427341e9be5a619b81b0b796"}}, "title": "Multiplex profiling of serum proteins in solution using barcoded antibody fragments and next generation sequencing.", "authors": [{"family": "Brofelth", "given": "Mattias", "initials": "M", "orcid": "0000-0003-1187-4005", "researcher": {"href": "https://publications.scilifelab.se/researcher/d07ff976b577400788e60a42a1a7bb5c.json"}}, {"family": "Ekstrand", "given": "Anna Isinger", "initials": "AI"}, {"family": "Gour", "given": "Shashank", "initials": "S"}, {"family": "Jansson", "given": "Ronnie", "initials": "R"}, {"family": "Hedhammar", "given": "My", "initials": "M"}, {"family": "Elleby", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Kvist", "given": "Anders", "initials": "A", "orcid": "0000-0002-1358-0695", "researcher": {"href": "https://publications.scilifelab.se/researcher/3e6b39bdc00c442f94caed782772a278.json"}}, {"family": "Wingren", "given": "Christer", "initials": "C"}, {"family": "Axelsson", "given": "Ulrika", "initials": "U", "orcid": "0000-0002-3712-4897", "researcher": {"href": "https://publications.scilifelab.se/researcher/9c96993814854e10b98890f952ba1151.json"}}, {"family": "Borrebaeck", "given": "Carl A K", "initials": "CAK", "orcid": "0000-0003-2461-2354", "researcher": {"href": "https://publications.scilifelab.se/researcher/6fabeaf17da24138990ee896281fc4d5.json"}}], "type": "journal article", "published": "2020-07-03", "journal": {"title": "Commun Biol", "issn": "2399-3642", "volume": "3", "issue": "1", "pages": "339", "issn-l": "2399-3642"}, "abstract": "The composition of serum proteins is reflecting the current health status and can, with the right tools, be used to detect early signs of disease, such as an emerging cancer. An earlier diagnosis of cancer would greatly increase the chance of an improved outcome for the patients. However, there is still an unmet need for proficient tools to decipher the information in the blood proteome, which calls for further technological development. Here, we present a proof-of-concept study that demonstrates an alternative approach for multiplexed protein profiling of serum samples in solution, using DNA barcoded scFv antibody fragments and next generation sequencing. The outcome shows high accuracy when discriminating samples derived from pancreatic cancer patients and healthy controls and represents a scalable alternative for serum analysis.", "doi": "10.1038/s42003-020-1068-0", "pmid": "32620783", "labels": {"Clinical Genomics Lund": null, "Clinical Genomics": null}, "xrefs": [{"db": "pii", "key": "10.1038/s42003-020-1068-0"}, {"db": "pmc", "key": "PMC7334203"}, {"db": "figshare", "key": "10.6084/m9.figshare.12370106"}], "notes": [], "created": "2020-12-01T18:13:15.627Z", "modified": "2021-11-10T12:49:31.330Z"}, {"entity": "publication", "iuid": "91408d68992c46ec9a960d86551d53a4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/91408d68992c46ec9a960d86551d53a4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/91408d68992c46ec9a960d86551d53a4"}}, "title": "Diamond Blackfan anemia is mediated by hyperactive Nemo-like kinase.", "authors": [{"family": "Wilkes", "given": "M C", "initials": "MC", "orcid": "0000-0002-9600-6831", "researcher": {"href": "https://publications.scilifelab.se/researcher/ca84b03e6bf54c65a2b76fb3e64e0fbf.json"}}, {"family": "Siva", "given": "K", "initials": "K", "orcid": "0000-0001-9480-4496", "researcher": {"href": "https://publications.scilifelab.se/researcher/e1a374557b76413cb2e620349d1de2b0.json"}}, {"family": "Chen", "given": "J", "initials": "J", "orcid": "0000-0001-8516-0975", "researcher": {"href": "https://publications.scilifelab.se/researcher/93cf6eaa8a61475789a772d30f29d2e5.json"}}, {"family": "Varetti", "given": "G", "initials": "G"}, {"family": "Youn", "given": "M Y", "initials": "MY", "orcid": "0000-0002-8112-2346", "researcher": {"href": "https://publications.scilifelab.se/researcher/b0d57655fc0140e98bff8d5a38591a08.json"}}, {"family": "Chae", "given": "H", "initials": "H"}, {"family": "Ek", "given": "F", "initials": "F", "orcid": "0000-0002-5651-8445", "researcher": {"href": "https://publications.scilifelab.se/researcher/ad7f4358932945309129f9a6c16bedf3.json"}}, {"family": "Olsson", "given": "R", "initials": "R", "orcid": "0000-0002-7107-3472", "researcher": {"href": "https://publications.scilifelab.se/researcher/f3e5a72515bf44e98f43d4690c6e577e.json"}}, {"family": "Lundb\u00e4ck", "given": "T", "initials": "T"}, {"family": "Dever", "given": "D P", "initials": "DP", "orcid": "0000-0001-5966-4803", "researcher": {"href": "https://publications.scilifelab.se/researcher/26948c8bb03f49e38ac7a3a902e78818.json"}}, {"family": "Nishimura", "given": "T", "initials": "T", "orcid": "0000-0002-5425-1708", "researcher": {"href": "https://publications.scilifelab.se/researcher/2262afd615c94810b338de701266a1e8.json"}}, {"family": "Narla", "given": "A", "initials": "A"}, {"family": "Glader", "given": "B", "initials": "B", "orcid": "0000-0003-2092-6276", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d18e9cf455741ada3a80c925e1bd462.json"}}, {"family": "Nakauchi", "given": "H", "initials": "H", "orcid": "0000-0002-9841-6973", "researcher": {"href": "https://publications.scilifelab.se/researcher/05684f8f727b43109f4d79d5bfec7c33.json"}}, {"family": "Porteus", "given": "M H", "initials": "MH", "orcid": "0000-0002-3850-4648", "researcher": {"href": "https://publications.scilifelab.se/researcher/5b4f9245987d4111b06d16f2afc9bb12.json"}}, {"family": "Repellin", "given": "C E", "initials": "CE", "orcid": "0000-0002-6552-3318", "researcher": {"href": "https://publications.scilifelab.se/researcher/6e36d8ec30b64efba4c0a91752598cd4.json"}}, {"family": "Gazda", "given": "H T", "initials": "HT"}, {"family": "Lin", "given": "S", "initials": "S"}, {"family": "Serrano", "given": "M", "initials": "M", "orcid": "0000-0001-7177-9312", "researcher": {"href": "https://publications.scilifelab.se/researcher/68e6f5d0278d4a7da30286ac0a59b5e0.json"}}, {"family": "Flygare", "given": "J", "initials": "J", "orcid": "0000-0002-1962-5276", "researcher": {"href": "https://publications.scilifelab.se/researcher/0814225ca796418c82b446b1c8c91961.json"}}, {"family": "Sakamoto", "given": "K M", "initials": "KM"}], "type": "journal article", "published": "2020-07-03", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "11", "issue": "1", "pages": "3344"}, "abstract": "Diamond Blackfan Anemia (DBA) is a congenital bone marrow failure syndrome associated with ribosomal gene mutations that lead to ribosomal insufficiency. DBA is characterized by anemia, congenital anomalies, and cancer predisposition. Treatment for DBA is associated with significant morbidity. Here, we report the identification of Nemo-like kinase (NLK) as a potential target for DBA therapy. To identify new DBA targets, we screen for small molecules that increase erythroid expansion in mouse models of DBA. This screen identified a compound that inhibits NLK. Chemical and genetic inhibition of NLK increases erythroid expansion in mouse and human progenitors, including bone marrow cells from DBA patients. In DBA models and patient samples, aberrant NLK activation is initiated at the Megakaryocyte/Erythroid Progenitor (MEP) stage of differentiation and is not observed in non-erythroid hematopoietic lineages or healthy erythroblasts. We propose that NLK mediates aberrant erythropoiesis in DBA and is a potential target for therapy.", "doi": "10.1038/s41467-020-17100-z", "pmid": "32620751", "labels": {"Chemical Biology Consortium Sweden": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-17100-z"}, {"db": "pmc", "key": "PMC7334220"}], "notes": [], "created": "2022-03-24T08:52:06.800Z", "modified": "2025-10-17T13:04:28.288Z"}, {"entity": "publication", "iuid": "a1d31987288449ba8a738404fa44921b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a1d31987288449ba8a738404fa44921b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a1d31987288449ba8a738404fa44921b"}}, "title": "meQTL and ncRNA functional analyses of 102 GWAS-SNPs associated with depression implicate HACE1 and SHANK2 genes.", "authors": [{"family": "Ciuculete", "given": "Diana M", "initials": "DM", "orcid": "0000-0001-6377-0270", "researcher": {"href": "https://publications.scilifelab.se/researcher/1facf036e83a4fd1934204cc1dc7ee4d.json"}}, {"family": "Voisin", "given": "Sarah", "initials": "S"}, {"family": "Kular", "given": "Lara", "initials": "L"}, {"family": "Jonsson", "given": "J\u00f6rgen", "initials": "J"}, {"family": "Rask-Andersen", "given": "Mathias", "initials": "M"}, {"family": "Mwinyi", "given": "Jessica", "initials": "J"}, {"family": "Schi\u00f6th", "given": "Helgi B", "initials": "HB"}], "type": "journal article", "published": "2020-07-02", "journal": {"title": "Clin Epigenetics", "issn": "1868-7083", "volume": "12", "issue": "1", "pages": "99", "issn-l": "1868-7075"}, "abstract": "Little is known about how genetics and epigenetics interplay in depression. Evidence suggests that genetic variants may change vulnerability to depression by modulating DNA methylation (DNAm) and non-coding RNA (ncRNA) levels. Therefore, the aim of the study was to investigate the effect of the genetic variation, previously identified in the largest genome-wide association study for depression, on proximal DNAm and ncRNA levels.\n\nWe performed DNAm quantitative trait locus (meQTL) analysis in two independent cohorts (total n = 435 healthy individuals), testing associations between 102 single-nucleotide polymorphisms (SNPs) and DNAm levels in whole blood. We identified and replicated 64 SNP-CpG pairs (padj. < 0.05) with meQTL effect. Lower DNAm at cg02098413 located in the HACE1 promoter conferred by the risk allele (C allele) at rs1933802 was associated with higher risk for depression (praw = 0.014, DNAm = 2.3%). In 1202 CD14+ cells sorted from blood, DNAm at cg02088412 positively correlated with HACE1 mRNA expression. Investigation in postmortem brain tissue of adults diagnosed with major depressive disorder (MDD) indicated 1% higher DNAm at cg02098413 in neurons and lower HACE1 mRNA expression in CA1 hippocampus of MDD patients compared with healthy controls (p = 0.008 and 0.012, respectively). Expression QTL analysis in blood of 74 adolescent revealed that hsa-miR-3664-5p was associated with rs7117514 (SHANK2) (padj. = 0.015, mRNA difference = 5.2%). Gene ontology analysis of the miRNA target genes highlighted implication in neuronal processes.\n\nCollectively, our findings from a multi-tissue (blood and brain) and multi-layered (genetic, epigenetic, transcriptomic) approach suggest that genetic factors may influence depression by modulating DNAm and miRNA levels. Alterations at HACE1 and SHANK2 loci imply potential mechanisms, such as oxidative stress in the brain, underlying depression. Our results deepened the knowledge of molecular mechanisms in depression and suggest new epigenetic targets that should be further evaluated.", "doi": "10.1186/s13148-020-00884-8", "pmid": "32616021", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s13148-020-00884-8"}, {"db": "pmc", "key": "PMC7333393"}], "notes": [], "created": "2020-08-04T14:50:04.126Z", "modified": "2024-01-16T13:48:42.216Z"}, {"entity": "publication", "iuid": "55dcf41e17e8459fb3c49cd79e48f71c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/55dcf41e17e8459fb3c49cd79e48f71c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/55dcf41e17e8459fb3c49cd79e48f71c"}}, "title": "Y-Chromosome Variation in Southern African Khoe-San Populations Based on Whole-Genome Sequences.", "authors": [{"family": "Naidoo", "given": "Thijessen", "initials": "T"}, {"family": "Xu", "given": "Jingzi", "initials": "J"}, {"family": "Vicente", "given": "M\u00e1rio", "initials": "M"}, {"family": "Malmstr\u00f6m", "given": "Helena", "initials": "H"}, {"family": "Soodyall", "given": "Himla", "initials": "H"}, {"family": "Jakobsson", "given": "Mattias", "initials": "M", "orcid": "0000-0001-7840-7853", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a4abe0fcb20492d9ec849c9fbf58a71.json"}}, {"family": "Schlebusch", "given": "Carina M", "initials": "CM", "orcid": "0000-0002-8160-9621", "researcher": {"href": "https://publications.scilifelab.se/researcher/682f10853c1145649b8c76680605dd9b.json"}}], "type": "comparative study", "published": "2020-07-01", "journal": {"title": "Genome Biol Evol", "issn": "1759-6653", "issn-l": "1759-6653", "volume": "12", "issue": "7", "pages": "1031-1039"}, "abstract": "Although the human Y chromosome has effectively shown utility in uncovering facets of human evolution and population histories, the ascertainment bias present in early Y-chromosome variant data sets limited the accuracy of diversity and TMRCA estimates obtained from them. The advent of next-generation sequencing, however, has removed this bias and allowed for the discovery of thousands of new variants for use in improving the Y-chromosome phylogeny and computing estimates that are more accurate. Here, we describe the high-coverage sequencing of the whole Y chromosome in a data set of 19 male Khoe-San individuals in comparison with existing whole Y-chromosome sequence data. Due to the increased resolution, we potentially resolve the source of haplogroup B-P70 in the Khoe-San, and reconcile recently published haplogroup A-M51 data with the most recent version of the ISOGG Y-chromosome phylogeny. Our results also improve the positioning of tentatively placed new branches of the ISOGG Y-chromosome phylogeny. The distribution of major Y-chromosome haplogroups in the Khoe-San and other African groups coincide with the emerging picture of African demographic history; with E-M2 linked to the agriculturalist Bantu expansion, E-M35 linked to pastoralist eastern African migrations, B-M112 linked to earlier east-south gene flow, A-M14 linked to shared ancestry with central African rainforest hunter-gatherers, and A-M51 potentially unique to the Khoe-San.", "doi": "10.1093/gbe/evaa098", "pmid": "32697300", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "5874966"}, {"db": "pmc", "key": "PMC7375190"}], "notes": [], "created": "2020-12-08T23:25:49.670Z", "modified": "2024-01-16T13:48:42.238Z"}, {"entity": "publication", "iuid": "7e73ccd6a0d54e61b8c4b59fbcb9150b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7e73ccd6a0d54e61b8c4b59fbcb9150b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7e73ccd6a0d54e61b8c4b59fbcb9150b"}}, "title": "Viral antigens elicit augmented immune responses in primary Sj\u00f6gren's syndrome.", "authors": [{"family": "Bj\u00f6rk", "given": "Albin", "initials": "A"}, {"family": "Thorlacius", "given": "Gudny Ella", "initials": "GE"}, {"family": "Mofors", "given": "Johannes", "initials": "J"}, {"family": "Richardsdotter Andersson", "given": "Elina", "initials": "E"}, {"family": "Ivanchenko", "given": "Margarita", "initials": "M"}, {"family": "Tingstr\u00f6m", "given": "Joanna", "initials": "J"}, {"family": "James", "given": "Tojo", "initials": "T"}, {"family": "Brokstad", "given": "Karl A", "initials": "KA"}, {"family": "Cox", "given": "Rebecca J", "initials": "RJ"}, {"family": "Jonsson", "given": "Roland", "initials": "R"}, {"family": "Kvarnstr\u00f6m", "given": "Marika", "initials": "M"}, {"family": "Wahren-Herlenius", "given": "Marie", "initials": "M", "orcid": "0000-0002-0915-7245", "researcher": {"href": "https://publications.scilifelab.se/researcher/a8451e7f5e6e4e4da0bace3dfafaeb38.json"}}], "type": "journal article", "published": "2020-07-01", "journal": {"title": "Rheumatology (Oxford)", "issn": "1462-0332", "issn-l": "1462-0324", "volume": "59", "issue": "7", "pages": "1651-1661"}, "abstract": "Infections have been suggested in the pathogenesis of primary SS (pSS). Systematic studies of immune responses to microbial antigens in vivo may be performed during vaccination. In the present study, we therefore longitudinally followed patients with pSS and controls during split-virion influenza vaccination to identify pSS-specific cellular, transcriptomic and serological responses.\n\nPatients without treatment (pSSUntr, n = 17), on hydroxychloroquine-treatment (pSSHCQ, n = 8), and healthy controls (n = 16) were included. Antibody titres were determined by ELISA. Plasma proteins were measured by proximity extension assay. Monocyte gene expression was assessed by Nanostring. Routine laboratory tests were performed and clinical disease symptoms were registered by questionnaires.\n\npSSUntr developed higher vaccine-specific IgG titres compared with controls. Notably, anti-Ro52 autoantibody titres increased in pSSUntr but remained unchanged in pSSHCQ. No changes in disease symptoms including EULAR Sj\u00f6gren's Syndrome Patient Reported Index score were registered. Twenty-four hours after vaccination, the leucocyte count in pSSUntr decreased, with a concomitant increase of CCL7 in plasma. Transcriptomic analysis in monocytes revealed differential vaccination-related expression of the NEMO/IKBKG gene, and its higher induced expression in pSSUntr associated with higher serological vaccine responses. Moreover, titres of vaccine-specific antibodies were associated with higher vaccination-induced NF-\u03baB signalling and higher steady-state IFN signatures in monocytes, and with the levels of several plasma proteins with soluble PD-1 displaying the strongest association.\n\nWe observed augmented innate and adaptive immune responses in pSS following viral antigen exposure suggesting an underlying hyper-responsiveness to immune challenges, supporting a role for infections driving the immunopathology and acting as environmental risk factor for pSS.", "doi": "10.1093/rheumatology/kez509", "pmid": "31665501", "labels": {"Clinical Biomarkers": "Service", "PLA and Single Cell Proteomics": "Service", "Affinity Proteomics Uppsala": "Service"}, "xrefs": [{"db": "pii", "key": "5610170"}], "notes": [], "created": "2020-01-23T16:04:34.697Z", "modified": "2023-04-14T13:55:52.372Z"}, {"entity": "publication", "iuid": "e3e2cdbba9384a1e8a930eb416eaeab3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e3e2cdbba9384a1e8a930eb416eaeab3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e3e2cdbba9384a1e8a930eb416eaeab3"}}, "title": "Loqusdb: added value of an observations database of local genomic variation.", "authors": [{"family": "Magnusson", "given": "M\u00e5ns", "initials": "M", "orcid": "0000-0002-0001-1047", "researcher": {"href": "https://publications.scilifelab.se/researcher/8e75a676a1bf4bfb80cf5ea579b44df0.json"}}, {"family": "Eisfeldt", "given": "Jesper", "initials": "J"}, {"family": "Nilsson", "given": "Daniel", "initials": "D"}, {"family": "Rosenbaum", "given": "Adam", "initials": "A"}, {"family": "Wirta", "given": "Valtteri", "initials": "V", "orcid": "0000-0003-3811-5439", "researcher": {"href": "https://publications.scilifelab.se/researcher/cba024b2e3c347f6b981922d984ad2d6.json"}}, {"family": "Lindstrand", "given": "Anna", "initials": "A"}, {"family": "Wedell", "given": "Anna", "initials": "A"}, {"family": "Stranneheim", "given": "Henrik", "initials": "H"}], "type": "journal article", "published": "2020-07-01", "journal": {"title": "BMC Bioinformatics", "issn": "1471-2105", "volume": "21", "issue": "1", "pages": "273", "issn-l": "1471-2105"}, "abstract": "Exome and genome sequencing is becoming the method of choice for rare disease diagnostics. One of the key challenges remaining is distinguishing the disease causing variants from the benign background variation. After analysis and annotation of the sequencing data there are typically thousands of candidate variants requiring further investigation. One of the most effective and least biased ways to reduce this number is to assess the rarity of a variant in any population. Currently, there are a number of reliable sources of information for major population frequencies when considering single nucleotide variants (SNVs) and small insertion and deletions (INDELs), with gnomAD as the most prominent public resource available. However, local variation or frequencies in sub-populations may be underrepresented in these public resources. In contrast, for structural variation (SV), the background frequency in the general population is more or less unknown mostly due to challenges in calling SVs in a consistent way. Keeping track of local variation is one way to overcome these problems and significantly reduce the number of potential disease causing variants retained for manual inspection, both for SNVs and SVs.\n\nHere, we present loqusdb, a tool to solve the challenge of keeping track of any type of variant observations from genome sequencing data. Loqusdb was designed to handle a large flow of samples and unlike other solutions, samples can be added continuously to the database without rebuilding it, facilitating improvements and additions. We assessed the added value of a local observations database using 98 samples annotated with information from a background of 888 unrelated individuals.\n\nWe show both how powerful SV analysis can be when filtering for population frequencies and how the number of apparently rare SNVs/INDELs can be reduced by adding local population information even after annotating the data with other large frequency databases, such as gnomAD. In conclusion, we show that a local frequency database is an attractive, and a necessary addition to the publicly available databases that facilitate the analysis of exome and genome data in a clinical setting.", "doi": "10.1186/s12859-020-03609-z", "pmid": "32611382", "labels": {"Clinical Genomics Stockholm": "Technology development", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Technology development"}, "xrefs": [{"db": "pii", "key": "10.1186/s12859-020-03609-z"}, {"db": "pmc", "key": "PMC7329469"}], "notes": [], "created": "2020-08-17T08:24:23.393Z", "modified": "2024-01-16T13:48:42.246Z"}, {"entity": "publication", "iuid": "b71fefd3189648368056856a895f0346", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b71fefd3189648368056856a895f0346.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b71fefd3189648368056856a895f0346"}}, "title": "Genetic Associations Between Childhood Psychopathology and Adult Depression and Associated Traits in 42 998 Individuals: A Meta-analysis.", "authors": [{"family": "Akingbuwa", "given": "Wonuola A", "initials": "WA"}, {"family": "Hammerschlag", "given": "Anke R", "initials": "AR"}, {"family": "Jami", "given": "Eshim S", "initials": "ES"}, {"family": "Allegrini", "given": "Andrea G", "initials": "AG"}, {"family": "Karhunen", "given": "Ville", "initials": "V"}, {"family": "Sallis", "given": "Hannah", "initials": "H"}, {"family": "Ask", "given": "Helga", "initials": "H"}, {"family": "Askeland", "given": "Ragna B", "initials": "RB"}, {"family": "Baselmans", "given": "Bart", "initials": "B"}, {"family": "Diemer", "given": "Elizabeth", "initials": "E"}, {"family": "Hagenbeek", "given": "Fiona A", "initials": "FA"}, {"family": "Havdahl", "given": "Alexandra", "initials": "A"}, {"family": "Hottenga", "given": "Jouke-Jan", "initials": "JJ"}, {"family": "Mbarek", "given": "Hamdi", "initials": "H"}, {"family": "Rivadeneira", "given": "Fernando", "initials": "F"}, {"family": "Tesli", "given": "Martin", "initials": "M"}, {"family": "van Beijsterveldt", "given": "Catharina", "initials": "C"}, {"family": "Breen", "given": "Gerome", "initials": "G"}, {"family": "Lewis", "given": "Cathryn M", "initials": "CM"}, {"family": "Thapar", "given": "Anita", "initials": "A"}, {"family": "Boomsma", "given": "Dorret I", "initials": "DI"}, {"family": "Kuja-Halkola", "given": "Ralf", "initials": "R"}, {"family": "Reichborn-Kjennerud", "given": "Ted", "initials": "T"}, {"family": "Magnus", "given": "Per", "initials": "P"}, {"family": "Rimfeld", "given": "Kaili", "initials": "K"}, {"family": "Ystrom", "given": "Eivind", "initials": "E"}, {"family": "Jarvelin", "given": "Marjo-Riitta", "initials": "MR"}, {"family": "Lichtenstein", "given": "Paul", "initials": "P"}, {"family": "Lundstrom", "given": "Sebastian", "initials": "S"}, {"family": "Munaf\u00f2", "given": "Marcus R", "initials": "MR"}, {"family": "Plomin", "given": "Robert", "initials": "R"}, {"family": "Tiemeier", "given": "Henning", "initials": "H"}, {"family": "Nivard", "given": "Michel G", "initials": "MG"}, {"family": "Bartels", "given": "Meike", "initials": "M"}, {"family": "Middeldorp", "given": "Christel M", "initials": "CM"}, {"family": "Bipolar Disorder and Major Depressive Disorder Working Groups of the Psychiatric Genomics Consortium", "given": "", "initials": ""}], "type": "journal article", "published": "2020-07-01", "journal": {"title": "JAMA Psychiatry", "issn": "2168-6238", "volume": "77", "issue": "7", "pages": "715-728", "issn-l": "2168-622X"}, "abstract": "Adult mood disorders are often preceded by behavioral and emotional problems in childhood. It is yet unclear what explains the associations between childhood psychopathology and adult traits.\n\nTo investigate whether genetic risk for adult mood disorders and associated traits is associated with childhood disorders.\n\nThis meta-analysis examined data from 7 ongoing longitudinal birth and childhood cohorts from the UK, the Netherlands, Sweden, Norway, and Finland. Starting points of data collection ranged from July 1985 to April 2002. Participants were repeatedly assessed for childhood psychopathology from ages 6 to 17 years. Data analysis occurred from September 2017 to May 2019.\n\nIndividual polygenic scores (PGS) were constructed in children based on genome-wide association studies of adult major depression, bipolar disorder, subjective well-being, neuroticism, insomnia, educational attainment, and body mass index (BMI).\n\nRegression meta-analyses were used to test associations between PGS and attention-deficit/hyperactivity disorder (ADHD) symptoms and internalizing and social problems measured repeatedly across childhood and adolescence and whether these associations depended on childhood phenotype, age, and rater.\n\nThe sample included 42 998 participants aged 6 to 17 years. Male participants varied from 43.0% (1040 of 2417 participants) to 53.1% (2434 of 4583 participants) by age and across all cohorts. The PGS of adult major depression, neuroticism, BMI, and insomnia were positively associated with childhood psychopathology (\u03b2 estimate range, 0.023-0.042 [95% CI, 0.017-0.049]), while associations with PGS of subjective well-being and educational attainment were negative (\u03b2, -0.026 to -0.046 [95% CI, -0.020 to -0.057]). There was no moderation of age, type of childhood phenotype, or rater with the associations. The exceptions were stronger associations between educational attainment PGS and ADHD compared with internalizing problems (\u0394\u03b2, 0.0561 [\u039495% CI, 0.0318-0.0804]; \u0394SE, 0.0124) and social problems (\u0394\u03b2, 0.0528 [\u039495% CI, 0.0282-0.0775]; \u0394SE, 0.0126), and between BMI PGS and ADHD and social problems (\u0394\u03b2, -0.0001 [\u039495% CI, -0.0102 to 0.0100]; \u0394SE, 0.0052), compared with internalizing problems (\u0394\u03b2, -0.0310 [\u039495% CI, -0.0456 to -0.0164]; \u0394SE, 0.0074). Furthermore, the association between educational attainment PGS and ADHD increased with age (\u0394\u03b2, -0.0032 [\u0394 95% CI, -0.0048 to -0.0017]; \u0394SE, 0.0008).\n\nResults from this study suggest the existence of a set of genetic factors influencing a range of traits across the life span with stable associations present throughout childhood. Knowledge of underlying mechanisms may affect treatment and long-term outcomes of individuals with psychopathology.", "doi": "10.1001/jamapsychiatry.2020.0527", "pmid": "32293669", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "2763801"}, {"db": "pmc", "key": "PMC7160753"}], "notes": [], "created": "2020-05-06T12:23:53.890Z", "modified": "2021-11-10T12:52:04.518Z"}, {"entity": "publication", "iuid": "ce6d56617d5243ee9bf1a8d1257c006e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ce6d56617d5243ee9bf1a8d1257c006e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ce6d56617d5243ee9bf1a8d1257c006e"}}, "title": "Transcriptomes from German shepherd dogs reveal differences in immune activity between atopic dermatitis affected and control skin.", "authors": [{"family": "Tengvall", "given": "K", "initials": "K", "orcid": "0000-0003-0424-3571", "researcher": {"href": "https://publications.scilifelab.se/researcher/59b02aaaf03b4cd39150c3034888c81d.json"}}, {"family": "Bergvall", "given": "K", "initials": "K"}, {"family": "Olsson", "given": "M", "initials": "M", "orcid": "0000-0002-7228-2575", "researcher": {"href": "https://publications.scilifelab.se/researcher/a544f6e122da4b1ebf7a2ad70fd5bceb.json"}}, {"family": "Ardesj\u00f6-Lundgren", "given": "B", "initials": "B"}, {"family": "Farias", "given": "F H G", "initials": "FHG", "orcid": "0000-0002-5215-7304", "researcher": {"href": "https://publications.scilifelab.se/researcher/1b8a07dda61d4fc3a3f837cdb5dbcd5a.json"}}, {"family": "Kierczak", "given": "M", "initials": "M", "orcid": "0000-0003-2629-5655", "researcher": {"href": "https://publications.scilifelab.se/researcher/6c13f96fb81f4ae2bfff5e91ac45388e.json"}}, {"family": "Hedhammar", "given": "\u00c5", "initials": "\u00c5", "orcid": "0000-0001-7048-3851", "researcher": {"href": "https://publications.scilifelab.se/researcher/fa01be589a4b4939a01c06ad57bfc356.json"}}, {"family": "Lindblad-Toh", "given": "K", "initials": "K", "orcid": "0000-0001-8338-0253", "researcher": {"href": "https://publications.scilifelab.se/researcher/e0063145f7d6476f80ab42f94833f4cf.json"}}, {"family": "Andersson", "given": "G", "initials": "G", "orcid": "0000-0001-5131-3144", "researcher": {"href": "https://publications.scilifelab.se/researcher/39ce81c314db47c8ad63c3ed38dffcb3.json"}}], "type": "journal article", "published": "2020-07-00", "journal": {"title": "Immunogenetics", "issn": "1432-1211", "volume": "72", "issue": "5", "pages": "315-323", "issn-l": "0093-7711"}, "abstract": "Canine atopic dermatitis (CAD) is an inflammatory and pruritic allergic skin disease with both genetic and environmental risk factors described. We performed mRNA sequencing of non-lesional axillary skin biopsies from nine German shepherd dogs. Obtained RNA sequences were mapped to the dog genome (CanFam3.1) and a high-quality skin transcriptome was generated with 23,510 expressed gene transcripts. Differentially expressed genes (DEGs) were defined by comparing three controls to five treated CAD cases. Using a leave-one-out analysis, we identified seven DEGs: five known to encode proteins with functions related to an activated immune system (CD209, CLEC4G, LOC102156842 (lipopolysaccharide-binding protein-like), LOC480601 (regakine-1-like), LOC479668 (haptoglobin-like)), one (OBP) encoding an odorant-binding protein potentially connected to rhinitis, and the last (LOC607095) encoding a novel long non-coding RNA. Furthermore, high mRNA expression of inflammatory genes was found in axillary skin from an untreated mild CAD case compared with healthy skin. In conclusion, we define genes with different expression patterns in CAD case skin helping us understand post-treatment atopic skin. Further studies in larger sample sets are warranted to confirm and to transfer these results into clinical practice.", "doi": "10.1007/s00251-020-01169-3", "pmid": "32556497", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1007/s00251-020-01169-3"}, {"db": "pmc", "key": "PMC7320941"}], "notes": [], "created": "2020-07-03T05:20:56.396Z", "modified": "2024-01-16T13:48:42.253Z"}, {"entity": "publication", "iuid": "820bcd5dc8a449449c0077bf2fa60e7a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/820bcd5dc8a449449c0077bf2fa60e7a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/820bcd5dc8a449449c0077bf2fa60e7a"}}, "title": "Tissue-specific isolation of Arabidopsis/plant mitochondria - IMTACT (isolation of mitochondria tagged in specific cell types).", "authors": [{"family": "Boussardon", "given": "Cl\u00e9ment", "initials": "C", "orcid": "0000-0001-8313-3535", "researcher": {"href": "https://publications.scilifelab.se/researcher/63dace73d3684bf3b48c13b58c5f777f.json"}}, {"family": "Przybyla-Toscano", "given": "Jonathan", "initials": "J", "orcid": "0000-0002-8053-6037", "researcher": {"href": "https://publications.scilifelab.se/researcher/813a60c6feae4c5da4396dc063650e1a.json"}}, {"family": "Carrie", "given": "Chris", "initials": "C", "orcid": "0000-0002-4240-4674", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a9f440fc0e94cbe956b35046cc13287.json"}}, {"family": "Keech", "given": "Olivier", "initials": "O", "orcid": "0000-0002-0546-7721", "researcher": {"href": "https://publications.scilifelab.se/researcher/cbfa829eb0b74b67aed7865dda0e15d3.json"}}], "type": "journal article", "published": "2020-07-00", "journal": {"title": "Plant J.", "issn": "1365-313X", "issn-l": "0960-7412", "volume": "103", "issue": "1", "pages": "459-473"}, "abstract": "Plant cells contain numerous subcompartments with clearly delineated metabolic functions. Mitochondria represent a very small fraction of the total cell volume and yet are the site of respiration and thus crucial for cells throughout all developmental stages of a plant's life. As such, their isolation from the rest of the cellular components is a basic requirement for numerous biochemical and physiological experiments. Although procedures exist to isolate plant mitochondria from different organs (i.e. leaves, roots, tubers, etc.), they are often tedious and do not provide resolution at the tissue level (i.e. phloem, mesophyll or pollen). Here, we present a novel method called IMTACT (isolation of mitochondria tagged in specific cell types), developed in Arabidopsis thaliana (Arabidopsis) that involves biotinylation of mitochondria in a tissue-specific manner using transgenic lines expressing a synthetic version of the OM64 (Outer Membrane 64) gene combined with BLRP and the BirA biotin ligase gene. Tissue specificity is achieved with cell-specific promoters (e.g. CAB3 and SUC2). Labeled mitochondria from crude extracts are retained by magnetic beads, allowing the simple and rapid isolation of highly pure and intact organelles from organs or specific tissues. For example, we could show that the mitochondrial population from mesophyll cells was significantly larger in size than the mitochondrial population isolated from leaf companion cells. To facilitate the applicability of this method in both wild-type and mutant Arabidopsis plants we generated a set of OM64-BLRP one-shot constructs with different selection markers and tissue-specific promoters.", "doi": "10.1111/tpj.14723", "pmid": "32057155", "labels": {"Integrated Microscopy Technologies Ume\u00e5": "Service"}, "xrefs": [], "notes": [], "created": "2020-12-10T11:23:19.952Z", "modified": "2022-04-01T14:38:12.313Z"}, {"entity": "publication", "iuid": "d75ee3f3f06b4002a4b80630b7b4d38b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d75ee3f3f06b4002a4b80630b7b4d38b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d75ee3f3f06b4002a4b80630b7b4d38b"}}, "title": "Support systems to guide clinical decision-making in precision oncology: The Cancer Core Europe Molecular Tumor Board Portal.", "authors": [{"family": "Tamborero", "given": "David", "initials": "D"}, {"family": "Dienstmann", "given": "Rodrigo", "initials": "R"}, {"family": "Rachid", "given": "Maan Haj", "initials": "MH", "orcid": "0000-0002-6380-209X", "researcher": {"href": "https://publications.scilifelab.se/researcher/6930cd01f3aa4e3e9233d98108f27c7d.json"}}, {"family": "Boekel", "given": "Jorrit", "initials": "J"}, {"family": "Baird", "given": "Richard", "initials": "R", "orcid": "0000-0001-7071-6483", "researcher": {"href": "https://publications.scilifelab.se/researcher/11aa354bf2f74c4d8c31f3e0faf650db.json"}}, {"family": "Bra\u00f1a", "given": "Irene", "initials": "I"}, {"family": "De Petris", "given": "Luigi", "initials": "L"}, {"family": "Yachnin", "given": "Jeffrey", "initials": "J"}, {"family": "Massard", "given": "Christophe", "initials": "C"}, {"family": "Opdam", "given": "Frans L", "initials": "FL"}, {"family": "Schlenk", "given": "Richard", "initials": "R"}, {"family": "Vernieri", "given": "Claudio", "initials": "C"}, {"family": "Garralda", "given": "Elena", "initials": "E"}, {"family": "Masucci", "given": "Michele", "initials": "M"}, {"family": "Villalobos", "given": "Xenia", "initials": "X"}, {"family": "Chavarria", "given": "Elena", "initials": "E"}, {"family": "Cancer Core Europe consortium", "given": "", "initials": ""}, {"family": "Calvo", "given": "Fabien", "initials": "F"}, {"family": "Fr\u00f6hling", "given": "Stefan", "initials": "S", "orcid": "0000-0001-7907-4595", "researcher": {"href": "https://publications.scilifelab.se/researcher/cd46d3f4c2084ce7922ceb0220b09277.json"}}, {"family": "Eggermont", "given": "Alexander", "initials": "A"}, {"family": "Apolone", "given": "Giovanni", "initials": "G"}, {"family": "Voest", "given": "Emile E", "initials": "EE", "orcid": "0000-0001-8249-9586", "researcher": {"href": "https://publications.scilifelab.se/researcher/e5a8340e3b0445bea291f971e1c2c75e.json"}}, {"family": "Caldas", "given": "Carlos", "initials": "C", "orcid": "0000-0003-3547-1489", "researcher": {"href": "https://publications.scilifelab.se/researcher/0cc09ee06f6c4391ba062ac65e85cb55.json"}}, {"family": "Tabernero", "given": "Josep", "initials": "J", "orcid": "0000-0002-2495-8139", "researcher": {"href": "https://publications.scilifelab.se/researcher/c9be0e16fc3f415e92754a6135bfc164.json"}}, {"family": "Ernberg", "given": "Ingemar", "initials": "I"}, {"family": "Rodon", "given": "Jordi", "initials": "J"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}], "type": "letter", "published": "2020-07-00", "journal": {"title": "Nat. Med.", "issn": "1546-170X", "issn-l": "1078-8956", "volume": "26", "issue": "7", "pages": "992-994"}, "abstract": null, "doi": "10.1038/s41591-020-0969-2", "pmid": "32632195", "labels": {"Clinical Genomics Stockholm": "Collaborative", "Global Proteomics and Proteogenomics": "Technology development", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41591-020-0969-2"}], "notes": [], "created": "2020-08-17T08:24:21.940Z", "modified": "2024-01-16T13:48:42.261Z"}, {"entity": "publication", "iuid": "06ddf1a806ae49bf8bdbf838910792de", "links": {"self": {"href": "https://publications.scilifelab.se/publication/06ddf1a806ae49bf8bdbf838910792de.json"}, "display": {"href": "https://publications.scilifelab.se/publication/06ddf1a806ae49bf8bdbf838910792de"}}, "title": "Serum Metabolites in Hand-Arm Vibration Exposed Workers.", "authors": [{"family": "Vihlborg", "given": "Per", "initials": "P"}, {"family": "Graff", "given": "P\u00e5l", "initials": "P"}, {"family": "Hagenbj\u00f6rk", "given": "Annika", "initials": "A"}, {"family": "Hadr\u00e9vi", "given": "Jenny", "initials": "J"}, {"family": "Bryngelsson", "given": "Ing-Liss", "initials": "IL"}, {"family": "Eriksson", "given": "K\u00e5re", "initials": "K"}], "type": "journal article", "published": "2020-07-00", "journal": {"title": "J Occup Environ Med", "issn": "1536-5948", "volume": "62", "issue": "7", "pages": "460-465", "issn-l": null}, "abstract": "To investigate whether low molecular organic biomarkers could be identified in blood samples from vibration exposed workers using a metabolomics.\n\nThe study population consisted of 38 metalworkers. All participants underwent a standardized medical examination. Blood samples were collected before and after work shift and analyzed with gas chromatography time-of-flight mass spectrometry. Multivariate modeling (orthogonal partial least-squares analysis with discriminant analysis [OPLS-DA]) were used to verify differences in metabolic profiles.\n\nTwenty-two study participants reported vascular symptoms judged as vibration-related. The metabolic profile from participants with vibration-induced white fingers (VWF) was distinctly separated from participants without VWF, both before and after vibration exposure.\n\nMetabolites that differed between the groups were identified both before and after exposure. Some of these metabolites might be indicators of health effects from exposure to vibrations. This is the first time that a metabolomic approach has been used in workers exposed to vibrations.", "doi": "10.1097/JOM.0000000000001864", "pmid": "32730020", "labels": {"Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pii", "key": "00043764-202007000-00002"}, {"db": "pmc", "key": "PMC7337105"}], "notes": [], "created": "2020-12-11T12:05:22.953Z", "modified": "2025-10-17T13:03:16.766Z"}, {"entity": "publication", "iuid": "e560b4e282614a85a6050f7d34ab5a36", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e560b4e282614a85a6050f7d34ab5a36.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e560b4e282614a85a6050f7d34ab5a36"}}, "title": "Proton pump inhibitors act with unprecedented potencies as inhibitors of the acetylcholine biosynthesizing enzyme-A plausible missing link for their association with incidence of dementia.", "authors": [{"family": "Kumar", "given": "Rajnish", "initials": "R"}, {"family": "Kumar", "given": "Amit", "initials": "A"}, {"family": "Nordberg", "given": "Agneta", "initials": "A"}, {"family": "L\u00e5ngstr\u00f6m", "given": "Bengt", "initials": "B"}, {"family": "Darreh-Shori", "given": "Taher", "initials": "T", "orcid": "0000-0003-1176-6258", "researcher": {"href": "https://publications.scilifelab.se/researcher/605963a6ce6e4517b0a153b89002b151.json"}}], "type": "journal article", "published": "2020-07-00", "journal": {"title": "Alzheimers Dement", "issn": "1552-5279", "volume": "16", "issue": "7", "pages": "1031-1042", "issn-l": null}, "abstract": "Several pharmacoepidemiological studies indicate that proton pump inhibitors (PPIs) significantly increase the risk of dementia. Yet, the underlying mechanism is not known. Here, we report the discovery of an unprecedented mode of action of PPIs that explains how PPIs may increase the risk of dementia.\n\nAdvanced in silico docking analyses and detailed enzymological assessments were performed on PPIs against the core-cholinergic enzyme, choline-acetyltransferase (ChAT), responsible for biosynthesis of acetylcholine (ACh).\n\nThis report shows compelling evidence that PPIs act as inhibitors of ChAT, with high selectivity and unprecedented potencies that lie far below their in vivo plasma and brain concentrations.\n\nGiven that accumulating evidence points at cholinergic dysfunction as a driving force of major dementia disorders, our findings mechanistically explain how prolonged use of PPIs may increase incidence of dementia. This call for restrictions for prolonged use of PPIs in elderly, and in patients with dementia or amyotrophic lateral sclerosis.", "doi": "10.1002/alz.12113", "pmid": "32383816", "labels": {"Protein Science Facility (PSF)": "Service"}, "xrefs": [], "notes": [], "created": "2024-04-03T14:17:01.245Z", "modified": "2024-04-03T14:17:01.288Z"}, {"entity": "publication", "iuid": "f47165e073754170af219aa11ee5f6b8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f47165e073754170af219aa11ee5f6b8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f47165e073754170af219aa11ee5f6b8"}}, "title": "Proteomic analysis of follicular fluid during human ovulation.", "authors": [{"family": "Zakerkish", "given": "Farnosh", "initials": "F"}, {"family": "Br\u00e4nnstr\u00f6m", "given": "Mats", "initials": "M", "orcid": "0000-0002-6081-9101", "researcher": {"href": "https://publications.scilifelab.se/researcher/3349b0acffde45d3807643f8d6a61e06.json"}}, {"family": "Carlsohn", "given": "Elisabet", "initials": "E"}, {"family": "Sihlbom", "given": "Carina", "initials": "C"}, {"family": "van der Post", "given": "Sjoerd", "initials": "S"}, {"family": "Thoroddsen", "given": "Asgeir", "initials": "A"}], "type": "journal article", "published": "2020-07-00", "journal": {"volume": "99", "issn": "1600-0412", "issue": "7", "title": "Acta Obstet Gynecol Scand", "pages": "917-924", "issn-l": "0001-6349"}, "abstract": "Human ovulation is a biologically complex process that involves several biochemical factors, promoting follicular rupture and release of a fertilizable oocyte. Proteins which are present in follicular fluid at high concentrations during ovulation are likely to be active participants in the biochemical pathways of ovulation. The aim of the study was to identify, by use of a modern proteomic technique, proteins of human follicular fluid which are differentially regulated during ovulation of the natural menstrual cycle.\n\nThis prospective experimental study over 3 years included women planned for laparoscopic sterilization. During surgery, retrieval of the dominant follicle was performed either at the preovulatory stage or during ovulation. Four women of preovulatory phase and four women of ovulatory phase met the predetermined criteria of hormone levels for respective phases, and samples of these were finally included out of the 15 women operated. Follicular fluid was aspirated from the excised follicle and subjected to mass spectrometry with the isobaric tags for relative and absolute quantification (iTRAQ) technology for isobaric tagging of peptides. This enables simultaneous identification and quantification of proteins. The protein profiles of the follicular fluid of the preovulatory phase and the ovulatory phase were analyzed, and proteins that were present were identified.\n\nA total of 502 proteins were identified, several of which previously have not been identified in human follicular fluid. Of the 115 proteins that were found in all samples, 20 proteins were at higher levels during ovulation. These were inflammatory-related proteins, coagulation factors, proteins in lipid metabolism, complement factors and antioxidants. Five proteins were present in lower levels during ovulation, with three being enzymes and the other two proteins of lipid metabolism and iron transport.\n\nTwenty-five follicular fluid proteins, with differential regulation during ovulation, were identified in human follicular fluid of the natural menstrual cycle. These proteins may have essential roles in the ovulatory cascade.", "doi": "10.1111/aogs.13805", "pmid": "31945183", "labels": {"Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [], "notes": [], "created": "2020-01-27T22:40:51.450Z", "modified": "2024-01-16T13:46:30.943Z"}, {"entity": "publication", "iuid": "f005a36d6a6944bc939d90904088154d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f005a36d6a6944bc939d90904088154d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f005a36d6a6944bc939d90904088154d"}}, "title": "Pre- and postnatal Lactobacillus reuteri treatment alters DNA methylation of infant T helper cells.", "authors": [{"family": "Forsberg", "given": "Anna", "initials": "A"}, {"family": "Huoman", "given": "Johanna", "initials": "J", "orcid": "0000-0003-2509-2418", "researcher": {"href": "https://publications.scilifelab.se/researcher/471444d05e834a9b86a5a6d187da2c04.json"}}, {"family": "S\u00f6derholm", "given": "Simon", "initials": "S", "orcid": "0000-0001-5350-7102", "researcher": {"href": "https://publications.scilifelab.se/researcher/75f4744864904171b6a708e7a8d2b471.json"}}, {"family": "Bhai Mehta", "given": "Ratnesh", "initials": "R"}, {"family": "Nilsson", "given": "Lennart", "initials": "L", "orcid": "0000-0002-5680-6367", "researcher": {"href": "https://publications.scilifelab.se/researcher/19f74feeb54c4d588b879ea9e8843662.json"}}, {"family": "Abrahamsson", "given": "Thomas R", "initials": "TR"}, {"family": "Ernerudh", "given": "Jan", "initials": "J"}, {"family": "Gustafsson", "given": "Mika", "initials": "M"}, {"family": "Jenmalm", "given": "Maria C", "initials": "MC", "orcid": "0000-0002-2117-5366", "researcher": {"href": "https://publications.scilifelab.se/researcher/bf1f485192744e0c95ccecdb5471b577.json"}}], "type": "journal article", "published": "2020-07-00", "journal": {"title": "Pediatr Allergy Immunol", "issn": "1399-3038", "volume": "31", "issue": "5", "pages": "544-553", "issn-l": "0905-6157"}, "abstract": "Perinatal childhood exposures, including probiotic supplementation, may affect epigenetic modifications and impact on immune maturation and allergy development. The aim of this study was to assess the effects of pre- and postnatal Lactobacillus reuteri supplementation on DNA methylation in relation to immune maturation and allergy development.\n\nDNA methylation patterns were investigated for allergy-related T helper subsets using a locus-specific method and at a genome-wide scale using the Illumina 450K array. From a randomised, double-blind, placebo-controlled allergy prevention trial with pre- and postnatal probiotic supplementation, CD4+ T helper cells were obtained at birth (from cord blood), and 12 and 24 months of age (total (placebo/probiotics); locus-specific method: CB = 32 (17/15), 12 months = 24 (9/15), 24 months = 35 (15/20); Illumina: CB = 19 (10/9), 12 months = 10 (6/4), 24 months = 19(11/8)).\n\nComparing probiotics to placebo, the greatest genome-wide differential DNA methylation was observed at birth, where the majority of sites were hypomethylated, indicating transcriptional accessibility in the probiotic group. Bioinformatic analyses, including network analyses, revealed a module containing 91 genes, enriched for immune-related pathways such as chemotaxis, PI3K-Akt, MAPK and TGF-\u03b2 signalling. A majority of the module genes were associated with atopic manifestations (OR = 1.43, P = 2.4 \u00d7 10-6 ), and a classifier built on this model could predict allergy development (AUC = 0.78, P = 3.0 \u00d7 10e-3 ). Pathways such as IFN-\u03b3 signalling and T-cell activation were more hypermethylated at birth compared with later in life in both intervention groups over time, in line with DNA methylation patterns in the IFNG locus obtained by the locus-specific methodology.\n\nMaternal L. reuteri supplementation during pregnancy alters DNA methylation patterns in CD4+ T cells towards enhanced immune activation at birth, which may affect immune maturation and allergy development.", "doi": "10.1111/pai.13240", "pmid": "32150651", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [], "notes": [], "created": "2020-03-12T15:01:36.562Z", "modified": "2024-01-16T13:48:42.269Z"}, {"entity": "publication", "iuid": "3151402e81174e78aa46f7b04a581c27", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3151402e81174e78aa46f7b04a581c27.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3151402e81174e78aa46f7b04a581c27"}}, "title": "PHF1 fusions cause distinct gene expression and chromatin accessibility profiles in ossifying fibromyxoid tumors and mesenchymal cells.", "authors": [{"family": "Hofvander", "given": "Jakob", "initials": "J", "orcid": "0000-0002-8787-1866", "researcher": {"href": "https://publications.scilifelab.se/researcher/04bbf18317ad44d6b348996c8fdda63a.json"}}, {"family": "Jo", "given": "Vickie Y", "initials": "VY"}, {"family": "Fletcher", "given": "Christopher D M", "initials": "CDM"}, {"family": "Puls", "given": "Florian", "initials": "F"}, {"family": "Flucke", "given": "Uta", "initials": "U"}, {"family": "Nilsson", "given": "Jenny", "initials": "J"}, {"family": "Magnusson", "given": "Linda", "initials": "L"}, {"family": "Mertens", "given": "Fredrik", "initials": "F", "orcid": "0000-0002-6278-5232", "researcher": {"href": "https://publications.scilifelab.se/researcher/909230c16f7840a49798794167232e76.json"}}], "type": "journal article", "published": "2020-07-00", "journal": {"title": "Mod. Pathol.", "issn": "1530-0285", "volume": "33", "issue": "7", "pages": "1331-1340", "issn-l": "0893-3952"}, "abstract": "Ossifying fibromyxoid tumor (OFMT) is a soft tissue tumor frequently displaying gene fusions, most of which affect the PHF1 gene. PHF1 encodes plant homeodomain finger protein 1, which is involved in various processes regulating gene transcription, including those orchestrated by the polycomb repressor complex 2. Here, a series of 37 OFMTs, including 18 typical, 9 atypical, and 10 malignant variants, was analyzed with regard to transcriptomic features, gene fusion and copy number status, and/or single-nucleotide variants. The effects on gene expression and chromatin accessibility of three detected fusions (EP400-PHF1, MEAF6-PHF1, and PHF1-TFE3) were further evaluated in fibroblasts. Genomic imbalances showed a progression-related pattern, with more extensive copy number changes among atypical/malignant lesions than among typical OFMTs; loss of the RB1 gene was restricted to atypical/malignant OFMTs, occurring in one-third of the cases. RNA sequencing identified fusion transcripts in >80% of the cases analyzed, including a novel CSMD1-MEAF6. The gene-expression profile of OFMT was distinct from that of other soft tissue tumors, with extensive transcriptional upregulation of genes in OFMT. These findings were largely recapitulated in gene fusion-expressing fibroblast lines, suggesting that genes involved in, e.g., Wnt signaling and/or being regulated through trimethylation of lysine 27 in histone 3 (H3K27me3) are pivotal for OFMT development. The genes showing differentially higher expression in fusion-expressing cells paralleled increased chromatin accessibility, as revealed by ATAC sequencing. Thus, the present study suggests that OFMT develops through gene fusions that have extensive epigenetic consequences.", "doi": "10.1038/s41379-020-0457-8", "pmid": "31932680", "labels": {"Clinical Genomics Lund": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41379-020-0457-8"}], "notes": [], "created": "2021-11-23T13:06:59.306Z", "modified": "2021-11-23T13:06:59.338Z"}, {"entity": "publication", "iuid": "5d3afacdca744fef83a8b327dedfaf5c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5d3afacdca744fef83a8b327dedfaf5c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5d3afacdca744fef83a8b327dedfaf5c"}}, "title": "Odorant receptor phylogeny confirms conserved channels for sex pheromone and host plant signals in tortricid moths.", "authors": [{"family": "Gonzalez", "given": "Francisco", "initials": "F"}, {"family": "Borrero-Echeverry", "given": "Felipe", "initials": "F"}, {"family": "J\u00f3svai", "given": "J\u00falia K", "initials": "JK"}, {"family": "Strandh", "given": "Maria", "initials": "M"}, {"family": "Unelius", "given": "C Rikard", "initials": "CR"}, {"family": "T\u00f3th", "given": "Mikl\u00f3s", "initials": "M"}, {"family": "Witzgall", "given": "Peter", "initials": "P", "orcid": "0000-0002-4697-3380", "researcher": {"href": "https://publications.scilifelab.se/researcher/548d4ff93a3f488e8133e5f7b1f79097.json"}}, {"family": "Bengtsson", "given": "Marie", "initials": "M"}, {"family": "Walker", "given": "William B", "initials": "WB"}], "type": "journal article", "published": "2020-07-00", "journal": {"title": "Ecol Evol", "issn": "2045-7758", "volume": "10", "issue": "14", "pages": "7334-7348", "issn-l": "2045-7758"}, "abstract": "The search for mates and food is mediated by volatile chemicals. Insects sense food odorants and sex pheromones through odorant receptors (ORs) and pheromone receptors (PRs), which are expressed in olfactory sensory neurons. Molecular phylogenetics of ORs, informed by behavioral and functional data, generates sound hypotheses for the identification of semiochemicals driving olfactory behavior. Studying orthologous receptors and their ligands across taxa affords insights into the role of chemical communication in reproductive isolation and phylogenetic divergence. The female sex pheromone of green budworm moth Hedya nubiferana (Lepidoptera, Totricidae) is a blend of two unsaturated acetates, only a blend of both elicits male attraction. Females produce in addition codlemone, which is the sex pheromone of another tortricid, codling moth Cydia pomonella. Codlemone also attracts green budworm moth males. Concomitantly, green budworm and codling moth males are attracted to the host plant volatile pear ester. A congruent behavioral response to the same pheromone and plant volatile in two tortricid species suggests co-occurrence of dedicated olfactory channels. In codling moth, one PR is tuned to both compounds, the sex pheromone codlemone and the plant volatile pear ester. Our phylogenetic analysis finds that green budworm moth expresses an orthologous PR gene. Shared ancestry, and high levels of amino acid identity and sequence similarity, in codling and green budworm moth PRs offer an explanation for parallel attraction of both species to the same compounds. A conserved olfactory channel for a sex pheromone and a host plant volatile substantiates the alliance of social and habitat signals in insect chemical communication. Field attraction assays confirm that in silico investigations of ORs afford powerful predictions for an efficient identification of behavior-modifying semiochemicals, for an improved understanding of the mechanisms of host plant attraction in insect herbivores and for the further development of sustainable insect control.", "doi": "10.1002/ece3.6458", "pmid": "32760532", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "ECE36458"}, {"db": "pmc", "key": "PMC7391548"}], "notes": [], "created": "2020-12-07T16:29:50.620Z", "modified": "2024-01-16T13:48:42.276Z"}, {"entity": "publication", "iuid": "dfba8e4537274d90abb9a4c98eec18ae", "links": {"self": {"href": "https://publications.scilifelab.se/publication/dfba8e4537274d90abb9a4c98eec18ae.json"}, "display": {"href": "https://publications.scilifelab.se/publication/dfba8e4537274d90abb9a4c98eec18ae"}}, "title": "Meiofauna improve oxygenation and accelerate sulfide removal in the seasonally hypoxic seabed.", "authors": [{"family": "Bonaglia", "given": "Stefano", "initials": "S", "orcid": "0000-0003-4366-0677", "researcher": {"href": "https://publications.scilifelab.se/researcher/c02dd99f9fd14dd89d5c231260806720.json"}}, {"family": "Hedberg", "given": "Johanna", "initials": "J"}, {"family": "Marzocchi", "given": "Ugo", "initials": "U", "orcid": "0000-0002-4746-9944", "researcher": {"href": "https://publications.scilifelab.se/researcher/85d1ad4b2b3e48db9cc591f4574cb848.json"}}, {"family": "Iburg", "given": "Sven", "initials": "S"}, {"family": "Glud", "given": "Ronnie N", "initials": "RN", "orcid": "0000-0002-7069-893X", "researcher": {"href": "https://publications.scilifelab.se/researcher/c9598036867244f2a67d4041f179859c.json"}}, {"family": "Nascimento", "given": "Francisco J A", "initials": "FJA", "orcid": "0000-0003-3722-1360", "researcher": {"href": "https://publications.scilifelab.se/researcher/5c2cfb0d7a614432b9dfdfcfa3fc4644.json"}}], "type": "journal article", "published": "2020-07-00", "journal": {"title": "Mar Environ Res", "issn": "1879-0291", "volume": "159", "issue": null, "pages": "104968", "issn-l": null}, "abstract": "Oxygen depleted areas are widespread in the marine realm. Unlike macrofauna, meiofauna are abundant in hypoxic sediments. We studied to what extent meiofauna affect oxygen availability, sulfide removal and microbial communities. Meiofauna were extracted alive and added to intact sediments simulating abundance gradients previously reported in the area. A total of 324 porewater microprofiles were recorded over a 3-week incubation period and microbial community structure and cable bacteria densities were determined at the end of the experiment. At high abundances meiofauna activity deepened oxygen penetration by 85%, 59%, and 62% after 5, 14, and 22 days, respectively, compared to control sediment with scarce meiofauna. After 6 days, meiofauna increased the volume of oxidized, sulfide-free sediment by 68% and reduced sulfide fluxes from 8.8 to 0.4 mmol m-2 d-1. After 15 days, the difference with the control attenuated due to the presence of a cable bacteria population, which facilitated sulfides oxidation in all treatments. 16S rRNA gene analysis revealed that meiofauna affected microbial community structure (beta diversity). Thus, meiofauna bioturbation plays an important role in deepening oxygen penetration, counteracting euxinia and in structuring microbial diversity of hypoxic sediments. Co-existence with cable bacteria demonstrates neutralism interaction between these two ecosystem engineers.", "doi": "10.1016/j.marenvres.2020.104968", "pmid": "32662428", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S0141-1136(19)30836-0"}, {"db": "pmc", "key": "PMC7369627"}], "notes": [], "created": "2020-12-07T16:32:28.789Z", "modified": "2024-01-16T13:48:42.283Z"}, {"entity": "publication", "iuid": "7c5837e061f644338f1e4dfb79e6f034", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7c5837e061f644338f1e4dfb79e6f034.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7c5837e061f644338f1e4dfb79e6f034"}}, "title": "Inflammatory markers in women with postpartum depressive symptoms.", "authors": [{"family": "Br\u00e4nn", "given": "Emma", "initials": "E", "orcid": "0000-0001-9664-7973", "researcher": {"href": "https://publications.scilifelab.se/researcher/9a86e0c38c604461a4adfbf42d6e0fa3.json"}}, {"family": "Fransson", "given": "Emma", "initials": "E", "orcid": "0000-0001-9010-8522", "researcher": {"href": "https://publications.scilifelab.se/researcher/40848617174047c89e9e957a4c424410.json"}}, {"family": "White", "given": "Richard A", "initials": "RA"}, {"family": "Papadopoulos", "given": "Fotios C", "initials": "FC"}, {"family": "Edvinsson", "given": "\u00c5sa", "initials": "\u00c5"}, {"family": "Kamali-Moghaddam", "given": "Masood", "initials": "M"}, {"family": "Cunningham", "given": "Janet L", "initials": "JL"}, {"family": "Sundstr\u00f6m-Poromaa", "given": "Inger", "initials": "I"}, {"family": "Skalkidou", "given": "Alkistis", "initials": "A"}], "type": "journal article", "published": "2020-07-00", "journal": {"volume": "98", "issn": "1097-4547", "issue": "7", "pages": "1309-1321", "title": "J Neuro Res", "issn-l": "0360-4012"}, "abstract": "Postpartum depression (PPD) is a devastating disorder affecting not only more than 10% of all women giving birth, but also the baby, the family, and the society. Compiling evidence suggests the involvement of the immune system in the pathophysiology of major depression; yet, the immune response in perinatal depression is not as well studied. The aim of this study was to investigate the alterations in peripheral levels of inflammatory biomarkers in 169 Swedish women with and without depressive symptoms according to the Edinburgh postnatal depression scale or the M.I.N.I neuropsychiatric interview at eight weeks postpartum. Among the 70 markers analyzed with multiplex proximity extension assay, five were significantly elevated in women with postpartum depressive symptoms in the adjusted LASSO logistic regression analysis: Tumor necrosis factor ligand superfamily member (TRANCE) (OR-per 1 SD increase = 1.20), Hepatocyte growth factor (HGF) (OR = 1.17) Interleukin (IL)-18 (OR = 1.06), Fibroblast growth factor 23 (FGF-23) (OR = 1.25), and C-X-C motif chemokine 1 (CXCL1) (OR 1.11). These results indicate that women with PPD have elevated levels of some inflammatory biomarkers. It is, therefore, plausible that PPD is associated with a compromised adaptability of the immune system.", "doi": "10.1002/jnr.24312", "pmid": "30252150", "labels": {"Clinical Biomarkers": "Service", "PLA and Single Cell Proteomics": "Service", "Affinity Proteomics Uppsala": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [], "notes": [], "created": "2018-10-30T08:18:15.680Z", "modified": "2024-01-16T13:48:42.290Z"}, {"entity": "publication", "iuid": "314a90056bf7402a86bdc286439af0e5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/314a90056bf7402a86bdc286439af0e5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/314a90056bf7402a86bdc286439af0e5"}}, "title": "Identifying the \u2018unidentified\u2019 fungi: a global-scale long-read third-generation sequencing approach", "authors": [{"family": "Tedersoo", "given": "Leho", "initials": "L"}, {"family": "Anslan", "given": "Sten", "initials": "S"}, {"family": "Bahram", "given": "Mohammad", "initials": "M"}, {"family": "K\u00f5ljalg", "given": "Urmas", "initials": "U"}, {"family": "Abarenkov", "given": "Kessy", "initials": "K"}], "type": "journal-article", "published": "2020-07-00", "journal": {"title": "Fungal Diversity", "issn": "1560-2745", "issn-l": null, "volume": "103", "issue": "1", "pages": "273-293"}, "abstract": "Molecular identification methods, in particular high-throughput sequencing tools, have greatly improved our knowledge about fungal diversity and biogeography, but many of the recovered taxa from natural environments cannot be identified to species or even higher taxonomic levels. This study addresses the phylogenetic placement of previously unrecognized fungal groups by using two complementary approaches: (i) third-generation amplicon sequencing analysis of DNA from global soil samples, screening out ITS reads of\u2009<\u200990% similarity to other available Sanger sequences, and (ii) analysis of common fungal taxa that were previously indicated to be enigmatic in terms of taxonomic placement based on the ITS sequences alone (so-called top50 sequences). For the global soil samples, we chose to amplify the full rRNA gene operon using four partly overlapping amplicons and multiple newly developed primers or primer combinations that cover nearly all fungi and a vast majority of non-fungal eukaryotes. We extracted the rRNA 18S (SSU) and 28S (LSU) genes and performed phylogenetic analyses against carefully selected reference material. Both SSU and LSU analyses placed most soil sequences and top50 sequences to known orders and classes, but tens of monophyletic groups and single sequences remained outside described taxa. Furthermore, the LSU analyses recovered a few small groups of sequences that may potentially represent novel phyla. We conclude that rRNA genes-based phylogenetic analyses are efficient tools for determining phylogenetic relationships of fungal taxa that cannot be placed to any order or class using ITS sequences alone. However, in many instances, longer rRNA gene sequences and availability of both SSU and LSU reads are needed to improve taxonomic resolution. By leveraging third-generation sequencing from global soil samples, we successfully provided phylogenetic placement for many previously unidentified sequences and broadened our view on the fungal tree of life, with 10\u201320% new order-level taxa. In addition, the PacBio sequence data greatly extends fungal class-level information in reference databases.", "doi": "10.1007/s13225-020-00456-4", "pmid": null, "labels": {"NGI Uppsala (Uppsala Genome Center)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [], "notes": [], "created": "2020-09-15T06:24:22.672Z", "modified": "2021-11-10T12:38:00.128Z"}, {"entity": "publication", "iuid": "5cb7cdbae68246d59af83a96584bf906", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5cb7cdbae68246d59af83a96584bf906.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5cb7cdbae68246d59af83a96584bf906"}}, "title": "Growth-Inhibitory Activity of Bone Morphogenetic Protein 4 in Human Glioblastoma Cell Lines Is Heterogeneous and Dependent on Reduced SOX2 Expression.", "authors": [{"family": "Dalmo", "given": "Erika", "initials": "E", "orcid": "0000-0003-0272-9893", "researcher": {"href": "https://publications.scilifelab.se/researcher/fc28d8e2dc16417eafd87d3bd1a1229f.json"}}, {"family": "Johansson", "given": "Patrik", "initials": "P"}, {"family": "Niklasson", "given": "Mia", "initials": "M"}, {"family": "Gustavsson", "given": "Ida", "initials": "I"}, {"family": "Nelander", "given": "Sven", "initials": "S"}, {"family": "Westermark", "given": "Bengt", "initials": "B", "orcid": "0000-0001-7153-5545", "researcher": {"href": "https://publications.scilifelab.se/researcher/dbaf3a1cdd7d48e5ba9e147bfb5055b6.json"}}], "type": "journal article", "published": "2020-07-00", "journal": {"title": "Mol Cancer Res", "issn": "1541-7786", "volume": "18", "issue": "7", "pages": "981-991", "issn-l": null}, "abstract": "Glioblastoma multiforme continues to have a dismal prognosis. Even though detailed information on the genetic aberrations in cell signaling and cell-cycle checkpoint control is available, no effective targeted treatment has been developed. Despite the advanced molecular defects, glioblastoma cells may have remnants of normal growth-inhibitory pathways, such as the bone morphogenetic protein (BMP) signaling pathway. We have evaluated the growth-inhibitory effect of BMP4 across a broad spectrum of patient samples, using a panel of 40 human glioblastoma initiating cell (GIC) cultures. A wide range of responsiveness was observed. BMP4 sensitivity was positively correlated with a proneural mRNA expression profile, high SOX2 activity, and BMP4-dependent upregulation of genes associated with inhibition of the MAPK pathway, as demonstrated by gene set enrichment analysis. BMP4 response in sensitive cells was mediated by the canonical BMP receptor pathway involving SMAD1/5/9 phosphorylation and SMAD4 expression. SOX2 was consistently downregulated in BMP4-treated cells. Forced expression of SOX2 attenuated the BMP4 sensitivity including a reduced upregulation of MAPK-inhibitory genes, implying a functional relationship between SOX2 downregulation and sensitivity. The results show an extensive heterogeneity in BMP4 responsiveness among GICs and identify a BMP4-sensitive subgroup, in which SOX2 is a mediator of the response. IMPLICATIONS: Development of agonists targeting the BMP signaling pathway in glioblastoma is an attractive avenue toward a better treatment. Our study may help find biomarkers that predict the outcome of such treatment and enable stratification of patients.", "doi": "10.1158/1541-7786.MCR-19-0638", "pmid": "32234828", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "1541-7786.MCR-19-0638"}], "notes": [], "created": "2020-12-08T23:44:27.982Z", "modified": "2024-01-16T13:48:42.299Z"}, {"entity": "publication", "iuid": "f1ad03c52d0f4de4a17266b615dc643c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f1ad03c52d0f4de4a17266b615dc643c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f1ad03c52d0f4de4a17266b615dc643c"}}, "title": "Genomic epidemiology and antimicrobial resistance determinants of Neisseria gonorrhoeae isolates from Ukraine, 2013-2018.", "authors": [{"family": "Boiko", "given": "Iryna", "initials": "I"}, {"family": "Golparian", "given": "Daniel", "initials": "D"}, {"family": "Jacobsson", "given": "Susanne", "initials": "S"}, {"family": "Krynytska", "given": "Inna", "initials": "I"}, {"family": "Frankenberg", "given": "Arkadii", "initials": "A"}, {"family": "Shevchenko", "given": "Tetiana", "initials": "T"}, {"family": "Unemo", "given": "Magnus", "initials": "M"}], "type": "journal article", "published": "2020-07-00", "journal": {"title": "APMIS", "issn": "1600-0463", "issn-l": "0903-4641", "volume": "128", "issue": "7", "pages": "465-475"}, "abstract": "Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is a major health threat compromising the gonorrhoea treatment globally. AMR surveillance including whole genome sequencing (WGS)-based epidemiology provides ideal resolution to identify and describe AMR gonococcal clones, AMR determinants and populations, which can inform management guidelines and antimicrobial stewardship policies. Our aims were to, for the first time, elucidate the WGS-based epidemiology and characterize AMR determinants of gonococcal strains spreading in Ukraine, 2013-2018. Gonococcal isolates (n = 150) from Ternopil and Dnipro, Ukraine (2013-2018), were subjected to AMR testing (Etest) for eight antimicrobials and WGS. Overall, 11.3% of isolates were resistant to ciprofloxacin, 6.0% to tetracycline, and 0.7% to benzylpenicillin. No isolates were resistant to azithromycin, spectinomycin, ceftriaxone, or cefixime, but one isolate was bordering resistance to both cephalosporins. Twenty-five MLST STs, 50 NG-MAST STs, and 34 NG-STAR types were identified. The phylogenomic analysis revealed six main clusters, mostly associated with the internationally described multidrug-susceptible gonococcal lineage. Resistance to ciprofloxacin was associated with GyrA S91F and ParC S87R mutations; tetracyclines with rpsJ V57M and tetM; penicillins with mosaic penA-34.001 and \u03b2-lactamase; mtrR; PorB1b G101D, and PBP1 L421P mutations. One isolate of the multidrug-resistant NG-MAST ST1407, MLST ST1901 was found, which was bordering resistance to ceftriaxone and cefixime. The antimicrobial susceptibility of gonococcal strains spreading in Ternopil and Dnipro, Ukraine, in 2013-2018 was surprisingly high. Continued and expanded gonococcal AMR surveillance, ideally including WGS, in Ukraine is essential. This could inform action plans and public health policies to control the spread of AMR gonococcal strains in Ukraine.", "doi": "10.1111/apm.13060", "pmid": "32441045", "labels": {"Clinical Genomics \u00d6rebro": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [], "notes": [], "created": "2020-11-27T14:03:21.732Z", "modified": "2021-12-08T12:30:39.145Z"}, {"entity": "publication", "iuid": "8526e68a3e854ed392784e2c39f600aa", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8526e68a3e854ed392784e2c39f600aa.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8526e68a3e854ed392784e2c39f600aa"}}, "title": "Gastric Microbiota in a Low-Helicobacter pylori Prevalence General Population and Their Associations With Gastric Lesions.", "authors": [{"family": "Ndegwa", "given": "Nelson", "initials": "N"}, {"family": "Ploner", "given": "Alexander", "initials": "A"}, {"family": "Andersson", "given": "Anders F", "initials": "AF"}, {"family": "Zagai", "given": "Ulrika", "initials": "U"}, {"family": "Andreasson", "given": "Anna", "initials": "A"}, {"family": "Vieth", "given": "Michael", "initials": "M"}, {"family": "Talley", "given": "Nicholas J", "initials": "NJ"}, {"family": "Agreus", "given": "Lars", "initials": "L"}, {"family": "Ye", "given": "Weimin", "initials": "W"}], "type": "journal article", "published": "2020-07-00", "journal": {"title": "Clin Transl Gastroenterol", "issn": "2155-384X", "volume": "11", "issue": "7", "pages": "e00191", "issn-l": "2155-384X"}, "abstract": "Non-Helicobacter pylori microbiota might account for some cases with unexplained chronic gastritis that may in a minority eventually progress to gastric cancer through the Correa cascade. We characterized gastric microbiota by describing the normal stomach, compared it with early precancerous lesions and other disease states, and assessed whether H. pylori status affects bacterial diversity.\n\nIn a population-based study of those with and without gastrointestinal symptoms, cytology brush samples were collected during endoscopy from 316 individuals. Mucosal status was classified as normal mucosa (171), nonatrophic H. pylori gastritis (33), atrophic gastritis (12), or antral chemical gastritis (61). The 16S rRNA gene sequencing and analysis were performed to characterize the microbiota.\n\nMicrobiota in atrophic gastritis and nonatrophic H. pylori gastritis stomachs were dysbiotic and differed from those in the normal stomach (P = 0.001). The normal stomach had the highest microbial diversity, followed by antral chemical gastritis. The atrophic gastritis and chronic H. pylori gastritis groups had the lowest diversity, a difference that was statistically significant (P = 0.01). Besides H. pylori, non-H. pylori bacteria accounted for group differences. Microbial network analysis showed that the normal group network was most highly connected, whereas the H. pylori gastritis group had the lowest connection. We found an increasing positive co-occurrence of oral bacteria in the stomach because samples deviated from the normal network, some of which were pathogens. The H. pylori-negative group had the highest microbial diversity (Shannon index) compared with the H. pylori-positive group (P = 0.001).\n\nIn this low-H. pylori prevalence general population, the gastric mucosal microbiota of the normal stomach differed significantly from those with nonatrophic or atrophic gastritis. There was an increasing abundance of pathogenic bacteria from the normal state to early precancerous states.", "doi": "10.14309/ctg.0000000000000191", "pmid": "32764211", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "01720094-202007000-00013"}, {"db": "pmc", "key": "PMC7431247"}], "notes": [], "created": "2020-09-17T15:25:36.522Z", "modified": "2024-01-16T13:48:42.307Z"}, {"entity": "publication", "iuid": "9d7fcd3fe5d84966ab5d1e2cf5d5137b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9d7fcd3fe5d84966ab5d1e2cf5d5137b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9d7fcd3fe5d84966ab5d1e2cf5d5137b"}}, "title": "Female-biased gene flow between two species of Darwin's finches.", "authors": [{"family": "Lamichhaney", "given": "Sangeet", "initials": "S", "orcid": "0000-0003-4826-0349", "researcher": {"href": "https://publications.scilifelab.se/researcher/602a2f371eae45e4b9d8f9748f285ef4.json"}}, {"family": "Han", "given": "Fan", "initials": "F"}, {"family": "Webster", "given": "Matthew T", "initials": "MT", "orcid": "0000-0003-1141-2863", "researcher": {"href": "https://publications.scilifelab.se/researcher/579df0da95b94e5087512b76d7f1c058.json"}}, {"family": "Grant", "given": "B Rosemary", "initials": "BR"}, {"family": "Grant", "given": "Peter R", "initials": "PR"}, {"family": "Andersson", "given": "Leif", "initials": "L", "orcid": "0000-0002-4085-6968", "researcher": {"href": "https://publications.scilifelab.se/researcher/bd3343c12f994b1fabcae23027d3a76d.json"}}], "type": "journal article", "published": "2020-07-00", "journal": {"title": "Nat Ecol Evol", "issn": "2397-334X", "volume": "4", "issue": "7", "pages": "979-986", "issn-l": "2397-334X"}, "abstract": "The mosaic nature of hybrid genomes is well recognized, but little is known of how they are shaped initially by patterns of breeding, selection, recombination and differential incompatibilities. On the small Gal\u00e1pagos island of Daphne Major, two species of Darwin's finches, Geospiza fortis and G. scandens, hybridize rarely and back-cross bidirectionally with little or no loss of fitness under conditions of plentiful food. We used whole-genome sequences to compare genomes from periods before and after successful interbreeding followed by back-crossing. We inferred extensive introgression from G. fortis to G. scandens on autosomes and mitochondria but not on the Z chromosome. The unique combination of long-term field observations and genomic data shows that the reduction of gene flow for Z-linked loci primarily reflects female-biased gene flow, arising from a hybrid-male disadvantage in competition for high-quality territories and mates, rather than from genetic incompatibilities at Z-linked loci.", "doi": "10.1038/s41559-020-1183-9", "pmid": "32367030", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41559-020-1183-9"}], "notes": [], "created": "2020-07-03T05:28:11.615Z", "modified": "2024-01-16T13:48:42.318Z"}, {"entity": "publication", "iuid": "13e1498d084a4f158e6801550ebd42a1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/13e1498d084a4f158e6801550ebd42a1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/13e1498d084a4f158e6801550ebd42a1"}}, "title": "Facets of individual-specific health signatures determined from longitudinal plasma proteome profiling.", "authors": [{"family": "Dodig-Crnkovi\u0107", "given": "Tea", "initials": "T", "orcid": "0000-0002-2875-896X", "researcher": {"href": "https://publications.scilifelab.se/researcher/cf18af5b676b449693945249fc1767e4.json"}}, {"family": "Hong", "given": "Mun-Gwan", "initials": "MG", "orcid": "0000-0001-8603-8293", "researcher": {"href": "https://publications.scilifelab.se/researcher/5d66c199ece143a6ab15222d8b55e3ea.json"}}, {"family": "Thomas", "given": "Cecilia Engel", "initials": "CE"}, {"family": "H\u00e4ussler", "given": "Ragna S", "initials": "RS", "orcid": "0000-0003-1664-8875", "researcher": {"href": "https://publications.scilifelab.se/researcher/ca04d9b9132747efb7db0efb6e34756a.json"}}, {"family": "Bendes", "given": "Annika", "initials": "A"}, {"family": "Dale", "given": "Matilda", "initials": "M", "orcid": "0000-0002-5788-7744", "researcher": {"href": "https://publications.scilifelab.se/researcher/59306e7e902048829efb30599ee3d2b1.json"}}, {"family": "Edfors", "given": "Fredrik", "initials": "F"}, {"family": "Forsstr\u00f6m", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Magnusson", "given": "Patrik K E", "initials": "PKE"}, {"family": "Schuppe-Koistinen", "given": "Ina", "initials": "I"}, {"family": "Odeberg", "given": "Jacob", "initials": "J"}, {"family": "Fagerberg", "given": "Linn", "initials": "L"}, {"family": "Gummesson", "given": "Anders", "initials": "A"}, {"family": "Bergstr\u00f6m", "given": "G\u00f6ran", "initials": "G"}, {"family": "Uhl\u00e9n", "given": "Mathias", "initials": "M", "orcid": "0000-0002-4858-8056", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff81da3cb0cf4262873b993a1b06798c.json"}}, {"family": "Schwenk", "given": "Jochen M", "initials": "JM", "orcid": "0000-0001-8141-8449", "researcher": {"href": "https://publications.scilifelab.se/researcher/aba5822711b246b397fffacb7ae403b3.json"}}], "type": "journal article", "published": "2020-07-00", "journal": {"title": "EBioMedicine", "issn": "2352-3964", "issn-l": "2352-3964", "volume": "57", "issue": null, "pages": "102854"}, "abstract": "Precision medicine approaches aim to tackle diseases on an individual level through molecular profiling. Despite the growing knowledge about diseases and the reported diversity of molecular phenotypes, the descriptions of human health on an individual level have been far less elaborate.\n\nTo provide insights into the longitudinal protein signatures of well-being, we profiled blood plasma collected over one year from 101 clinically healthy individuals using multiplexed antibody assays. After applying an antibody validation scheme, we utilized > 700 protein profiles for in-depth analyses of the individuals' short-term health trajectories.\n\nWe found signatures of circulating proteomes to be highly individual-specific. Considering technical and longitudinal variability, we observed that 49% of the protein profiles were stable over one year. We also identified eight networks of proteins in which 11-242 proteins covaried over time. For each participant, there were unique protein profiles of which some could be explained by associations to genetic variants.\n\nThis observational and non-interventional study identifyed noticeable diversity among clinically healthy subjects, and facets of individual-specific signatures emerged by monitoring the variability of the circulating proteomes over time. To enable more personal hence precise assessments of health states, longitudinal profiling of circulating proteomes can provide a valuable component for precision medicine approaches.\n\nThis work was supported by the Erling Persson Foundation, the Swedish Heart and Lung Foundation, the Knut and Alice Wallenberg Foundation, Science for Life Laboratory, and the Swedish Research Council.", "doi": "10.1016/j.ebiom.2020.102854", "pmid": "32629387", "labels": {"Affinity Proteomics Stockholm": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S2352-3964(20)30229-2"}, {"db": "pmc", "key": "PMC7334812"}], "notes": [], "created": "2020-12-10T19:03:42.215Z", "modified": "2021-11-10T12:49:49.689Z"}, {"entity": "publication", "iuid": "ca335345d4104805803d58f9c0c2c4cd", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ca335345d4104805803d58f9c0c2c4cd.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ca335345d4104805803d58f9c0c2c4cd"}}, "title": "Dynamic allosteric communication pathway directing differential activation of the glucocorticoid receptor.", "authors": [{"family": "K\u00f6hler", "given": "C", "initials": "C", "orcid": "0000-0002-4347-3110", "researcher": {"href": "https://publications.scilifelab.se/researcher/1af8128ea267472e980d78545001c86c.json"}}, {"family": "Carlstr\u00f6m", "given": "G", "initials": "G", "orcid": "0000-0003-4981-2440", "researcher": {"href": "https://publications.scilifelab.se/researcher/866dc5a8666e4814ab4ae0f346d9d5d5.json"}}, {"family": "Gunnarsson", "given": "A", "initials": "A"}, {"family": "Weininger", "given": "U", "initials": "U", "orcid": "0000-0003-0841-8332", "researcher": {"href": "https://publications.scilifelab.se/researcher/24384408cc7b4c72bd496b452237d1a5.json"}}, {"family": "T\u00e5ngefjord", "given": "S", "initials": "S", "orcid": "0000-0002-3846-6637", "researcher": {"href": "https://publications.scilifelab.se/researcher/60570e5550a74340af123c498b33609d.json"}}, {"family": "Ullah", "given": "V", "initials": "V"}, {"family": "Lepist\u00f6", "given": "M", "initials": "M"}, {"family": "Karlsson", "given": "U", "initials": "U"}, {"family": "Papavoine", "given": "T", "initials": "T", "orcid": "0000-0002-2359-7159", "researcher": {"href": "https://publications.scilifelab.se/researcher/137909632b77412497f482eb806e342a.json"}}, {"family": "Edman", "given": "K", "initials": "K", "orcid": "0000-0002-2560-2388", "researcher": {"href": "https://publications.scilifelab.se/researcher/a06dff3734a943ca92bc47e3defe55b5.json"}}, {"family": "Akke", "given": "M", "initials": "M", "orcid": "0000-0002-2395-825X", "researcher": {"href": "https://publications.scilifelab.se/researcher/e36b418e03154b90a8722670bed9e81a.json"}}], "type": "journal article", "published": "2020-07-00", "journal": {"title": "Sci Adv", "issn": "2375-2548", "volume": "6", "issue": "29", "pages": "eabb5277", "issn-l": "2375-2548"}, "abstract": "Allosteric communication within proteins is a hallmark of biochemical signaling, but the dynamic transmission pathways remain poorly characterized. We combined NMR spectroscopy and surface plasmon resonance to reveal these pathways and quantify their energetics in the glucocorticoid receptor, a transcriptional regulator controlling development, metabolism, and immune response. Our results delineate a dynamic communication network of residues linking the ligand-binding pocket to the activation function-2 interface, where helix 12, a switch for transcriptional activation, exhibits ligand- and coregulator-dependent dynamics coupled to graded activation. The allosteric free energy responds to variations in ligand structure: subtle changes gradually tune allostery while preserving the transmission pathway, whereas substitution of the entire pharmacophore leads to divergent allosteric control by apparently rewiring the communication network. Our results provide key insights that should aid in the design of mechanistically differentiated ligands.", "doi": "10.1126/sciadv.abb5277", "pmid": "32832645", "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [{"db": "pii", "key": "abb5277"}, {"db": "pmc", "key": "PMC7439413"}], "notes": [], "created": "2020-12-11T09:09:31.901Z", "modified": "2025-10-17T13:03:56.813Z"}, {"entity": "publication", "iuid": "b66fd12de48f4f21864e07d215e2c52d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b66fd12de48f4f21864e07d215e2c52d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b66fd12de48f4f21864e07d215e2c52d"}}, "title": "Deactivation mechanism of Cu active sites in Cu/SSZ-13 \u2014 Phosphorus poisoning and the effect of hydrothermal aging", "authors": [{"family": "Wang", "given": "Aiyong", "initials": "A", "orcid": "0000-0002-4213-9735", "researcher": {"href": "https://publications.scilifelab.se/researcher/8ff55e8bbf7c488db2a27d4d482a92ed.json"}}, {"family": "Xie", "given": "Kunpeng", "initials": "K", "orcid": "0000-0001-7927-4167", "researcher": {"href": "https://publications.scilifelab.se/researcher/98c1026d4c1f487f8c4103d76195aa71.json"}}, {"family": "Bernin", "given": "Diana", "initials": "D", "orcid": "0000-0002-9611-2263", "researcher": {"href": "https://publications.scilifelab.se/researcher/7ad134b1d8ab41b8a8a3318801d92e10.json"}}, {"family": "Kumar", "given": "Ashok", "initials": "A"}, {"family": "Kamasamudram", "given": "Krishna", "initials": "K"}, {"family": "Olsson", "given": "Louise", "initials": "L", "orcid": "0000-0002-8308-0784", "researcher": {"href": "https://publications.scilifelab.se/researcher/0480749dd49d45919dae353a203fe6ef.json"}}], "type": "journal-article", "published": "2020-07-00", "journal": {"title": "Applied Catalysis B: Environmental", "issn": "0926-3373", "volume": "269", "issue": null, "pages": "118781", "issn-l": null}, "abstract": null, "doi": "10.1016/j.apcatb.2020.118781", "pmid": null, "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [], "notes": [], "created": "2020-12-11T09:04:16.545Z", "modified": "2025-10-17T13:03:56.825Z"}, {"entity": "publication", "iuid": "285f9366b9634a208fe7e42df7d762eb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/285f9366b9634a208fe7e42df7d762eb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/285f9366b9634a208fe7e42df7d762eb"}}, "title": "DNA demethylation regulates gene expression in IgE-activated mouse mast cells.", "authors": [{"family": "Paivandy", "given": "Aida", "initials": "A"}, {"family": "Grujic", "given": "Mirjana", "initials": "M"}, {"family": "Rafati", "given": "Nima", "initials": "N"}, {"family": "Pejler", "given": "Gunnar", "initials": "G", "orcid": "0000-0002-6779-391X", "researcher": {"href": "https://publications.scilifelab.se/researcher/97b2d5f8dec04bc3b7631370d77a2236.json"}}], "type": "letter", "published": "2020-07-00", "journal": {"title": "Allergy", "issn": "1398-9995", "volume": "75", "issue": "7", "pages": "1776-1780", "issn-l": "0105-4538"}, "abstract": null, "doi": "10.1111/all.14205", "pmid": "31995647", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [], "notes": [], "created": "2020-09-15T07:17:42.232Z", "modified": "2021-11-10T12:49:52.120Z"}, {"entity": "publication", "iuid": "8cb53a7450cc4a7e80432a058a5d263d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8cb53a7450cc4a7e80432a058a5d263d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8cb53a7450cc4a7e80432a058a5d263d"}}, "title": "Comparison of spleen transcriptomes of two wild rodent species reveals differences in the immune response against Borrelia afzelii.", "authors": [{"family": "Zhong", "given": "Xiuqin", "initials": "X", "orcid": "0000-0002-4772-4255", "researcher": {"href": "https://publications.scilifelab.se/researcher/a1847f16fd2a4d1cac925c7b89b70684.json"}}, {"family": "Lundberg", "given": "Max", "initials": "M", "orcid": "0000-0002-1895-3622", "researcher": {"href": "https://publications.scilifelab.se/researcher/5b6a6dafa8fe4371ab26ed02ca5a550c.json"}}, {"family": "R\u00e5berg", "given": "Lars", "initials": "L", "orcid": "0000-0001-5219-7448", "researcher": {"href": "https://publications.scilifelab.se/researcher/a732076e5acc4ede94cc864cd90c99f3.json"}}], "type": "journal article", "published": "2020-07-00", "journal": {"title": "Ecol Evol", "issn": "2045-7758", "volume": "10", "issue": "13", "pages": "6421-6434", "issn-l": "2045-7758"}, "abstract": "Different host species often differ considerably in susceptibility to a given pathogen, but the causes of such differences are rarely known. The natural hosts of the tick-transmitted bacterium Borrelia afzelii, which is one of causative agents of Lyme borreliosis in humans, include a variety of small mammals like voles and mice. Previous studies have shown that B. afzelii-infected bank voles (Myodes glareolus) have about ten times higher bacterial load than infected yellow-necked mice (Apodemus flavicollis), indicating that these two species differ in resistance. In this study, we compared the immune response to B. afzelii infection in these host species by using RNA sequencing to quantify gene expression in spleen. Gene set enrichment analysis (GSEA) showed that several immune pathways were down-regulated in infected animals in both bank voles and yellow-necked mice. Moreover, IFN\u03b1 response was up-regulated in B. afzelii-infected yellow-necked mice, while IL6 signaling and the complement pathway were down-regulated in infected bank voles; differences in regulation of these three pathways between bank voles and yellow-necked mice could thus contribute to the difference in resistance to B. afzelii between the species. This study provides knowledge of gene expression induced by a zoonotic pathogen in its natural host, and possible species-specific regulation of immune responses associated with resistance.", "doi": "10.1002/ece3.6377", "pmid": "32724523", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "ECE36377"}, {"db": "pmc", "key": "PMC7381583"}, {"db": "Dryad", "key": "10.5061/dryad.t1g1jwt02"}], "notes": [], "created": "2020-12-07T16:29:59.033Z", "modified": "2024-01-16T13:48:42.326Z"}, {"entity": "publication", "iuid": "2370c21b8e884c9c888bbf50eae7c900", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2370c21b8e884c9c888bbf50eae7c900.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2370c21b8e884c9c888bbf50eae7c900"}}, "title": "Base-pair conformational switch modulates miR-34a targeting of Sirt1 mRNA.", "authors": [{"family": "Baronti", "given": "Lorenzo", "initials": "L", "orcid": "0000-0001-5393-3822", "researcher": {"href": "https://publications.scilifelab.se/researcher/c20ff7084a744df5873160b73f547160.json"}}, {"family": "Guzzetti", "given": "Ileana", "initials": "I"}, {"family": "Ebrahimi", "given": "Parisa", "initials": "P", "orcid": "0000-0002-1809-2316", "researcher": {"href": "https://publications.scilifelab.se/researcher/477b1bbbb0894858a774ecc52ff11c63.json"}}, {"family": "Friebe Sandoz", "given": "Sarah", "initials": "S"}, {"family": "Steiner", "given": "Emilie", "initials": "E"}, {"family": "Schlagnitweit", "given": "Judith", "initials": "J"}, {"family": "Fromm", "given": "Bastian", "initials": "B"}, {"family": "Silva", "given": "Luis", "initials": "L", "orcid": "0000-0003-1684-9271", "researcher": {"href": "https://publications.scilifelab.se/researcher/efe5f2c1f17046c393abe0bc0839b837.json"}}, {"family": "Fontana", "given": "Carolina", "initials": "C", "orcid": "0000-0002-7362-2180", "researcher": {"href": "https://publications.scilifelab.se/researcher/4edb65adc22249c9a3cbea35b2713cdd.json"}}, {"family": "Chen", "given": "Alan A", "initials": "AA", "orcid": "0000-0001-8246-2935", "researcher": {"href": "https://publications.scilifelab.se/researcher/879c0a3b32254050a7052e3a9e96e5f5.json"}}, {"family": "Petzold", "given": "Katja", "initials": "K", "orcid": "0000-0001-9470-0347", "researcher": {"href": "https://publications.scilifelab.se/researcher/946f0162cdb0411493968f363c943ad5.json"}}], "type": "journal article", "published": "2020-07-00", "journal": {"title": "Nature", "issn": "1476-4687", "volume": "583", "issue": "7814", "pages": "139-144", "issn-l": "0028-0836"}, "abstract": "MicroRNAs (miRNAs) regulate the levels of translation of messenger RNAs (mRNAs). At present, the major parameter that can explain the selection of the target mRNA and the efficiency of translation repression is the base pairing between the 'seed' region of the miRNA and its counterpart mRNA1. Here we use R1\u03c1 relaxation-dispersion nuclear magnetic resonance2 and molecular simulations3 to reveal a dynamic switch-based on the rearrangement of a single base pair in the miRNA-mRNA duplex-that elongates a weak five-base-pair seed to a complete seven-base-pair seed. This switch also causes coaxial stacking of the seed and supplementary helix fitting into human Argonaute 2 protein (Ago2), reminiscent of an active state in prokaryotic Ago4,5. Stabilizing this transient state leads to enhanced repression of the target mRNA in cells, revealing the importance of this miRNA-mRNA structure. Our observations tie together previous findings regarding the stepwise miRNA targeting process from an initial 'screening' state to an 'active' state, and unveil the role of the RNA duplex beyond the seed in Ago2.", "doi": "10.1038/s41586-020-2336-3", "pmid": "32461691", "labels": {"Protein Science Facility (PSF)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41586-020-2336-3"}], "notes": [], "created": "2020-09-08T08:54:44.502Z", "modified": "2021-11-10T12:49:54.697Z"}, {"entity": "publication", "iuid": "e6d4a1a9c58c4dc9b7fa3e8355f3f587", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e6d4a1a9c58c4dc9b7fa3e8355f3f587.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e6d4a1a9c58c4dc9b7fa3e8355f3f587"}}, "title": "Accounting for environmental variation in co-occurrence modelling reveals the importance of positive interactions in root-associated fungal communities.", "authors": [{"family": "Abrego", "given": "Nerea", "initials": "N", "orcid": "0000-0001-6347-6127", "researcher": {"href": "https://publications.scilifelab.se/researcher/547484556cdb43088e953f78e97f416e.json"}}, {"family": "Roslin", "given": "Tomas", "initials": "T", "orcid": "0000-0002-2957-4791", "researcher": {"href": "https://publications.scilifelab.se/researcher/04d92328b67e47ab82257567c07cf12f.json"}}, {"family": "Huotari", "given": "Tea", "initials": "T"}, {"family": "Tack", "given": "Ayco J M", "initials": "AJM", "orcid": "0000-0002-3550-1070", "researcher": {"href": "https://publications.scilifelab.se/researcher/7f9cf8fde705481281edab32bc9156e5.json"}}, {"family": "Lindahl", "given": "Bj\u00f6rn D", "initials": "BD", "orcid": "0000-0002-3384-4547", "researcher": {"href": "https://publications.scilifelab.se/researcher/b7a40688d33545a19c3c666940bda255.json"}}, {"family": "Tikhonov", "given": "Gleb", "initials": "G", "orcid": "0000-0003-3040-0307", "researcher": {"href": "https://publications.scilifelab.se/researcher/83ce2dc9d0304b0bb08de20ab8354446.json"}}, {"family": "Somervuo", "given": "Panu", "initials": "P", "orcid": "0000-0003-3121-4047", "researcher": {"href": "https://publications.scilifelab.se/researcher/bc4e5cf7203b4a2084034b7569dcd02c.json"}}, {"family": "Schmidt", "given": "Niels Martin", "initials": "NM", "orcid": "0000-0002-4166-6218", "researcher": {"href": "https://publications.scilifelab.se/researcher/0248915d131f49869c9c34312664b57a.json"}}, {"family": "Ovaskainen", "given": "Otso", "initials": "O", "orcid": "0000-0001-9750-4421", "researcher": {"href": "https://publications.scilifelab.se/researcher/c754e5e5dc4244908a350074724a0418.json"}}], "type": "journal article", "published": "2020-07-00", "journal": {"title": "Mol. Ecol.", "issn": "1365-294X", "volume": "29", "issue": "14", "pages": "2736-2746", "issn-l": "0962-1083"}, "abstract": "Understanding the role of interspecific interactions in shaping ecological communities is one of the central goals in community ecology. In fungal communities, measuring interspecific interactions directly is challenging because these communities are composed of large numbers of species, many of which are unculturable. An indirect way of assessing the role of interspecific interactions in determining community structure is to identify the species co-occurrences that are not constrained by environmental conditions. In this study, we investigated co-occurrences among root-associated fungi, asking whether fungi co-occur more or less strongly than expected based on the environmental conditions and the host plant species examined. We generated molecular data on root-associated fungi of five plant species evenly sampled along an elevational gradient at a high arctic site. We analysed the data using a joint species distribution modelling approach that allowed us to identify those co-occurrences that could be explained by the environmental conditions and the host plant species, as well as those co-occurrences that remained unexplained and thus more probably reflect interactive associations. Our results indicate that not only negative but also positive interactions play an important role in shaping microbial communities in arctic plant roots. In particular, we found that mycorrhizal fungi are especially prone to positively co-occur with other fungal species. Our results bring new understanding to the structure of arctic interaction networks by suggesting that interactions among root-associated fungi are predominantly positive.", "doi": "10.1111/mec.15516", "pmid": "32562300", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "Dryad", "key": "10.5061/dryad.9kd51c5dp"}], "notes": [], "created": "2020-09-15T06:18:10.682Z", "modified": "2021-11-10T12:49:55.875Z"}, {"entity": "publication", "iuid": "a5a1963fd516402bbc91e16b77379601", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a5a1963fd516402bbc91e16b77379601.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a5a1963fd516402bbc91e16b77379601"}}, "title": "A framework to assess the quality and impact of bioinformatics training across ELIXIR.", "authors": [{"family": "Gurwitz", "given": "Kim T", "initials": "KT", "orcid": "0000-0003-1992-5073", "researcher": {"href": "https://publications.scilifelab.se/researcher/3a5bf8910c22409fa3c8121755388d0f.json"}}, {"family": "Singh Gaur", "given": "Prakash", "initials": "P", "orcid": "0000-0003-3272-628X", "researcher": {"href": "https://publications.scilifelab.se/researcher/6e1090dcab7e4216960cf7798523179f.json"}}, {"family": "Bellis", "given": "Louisa J", "initials": "LJ", "orcid": "0000-0001-9581-870X", "researcher": {"href": "https://publications.scilifelab.se/researcher/865db60afe8b400aaf33d1c9c8648634.json"}}, {"family": "Larcombe", "given": "Lee", "initials": "L", "orcid": "0000-0003-3150-6445", "researcher": {"href": "https://publications.scilifelab.se/researcher/79426101140d4588bb672e154e5590e2.json"}}, {"family": "Alloza", "given": "Eva", "initials": "E", "orcid": "0000-0001-8385-9336", "researcher": {"href": "https://publications.scilifelab.se/researcher/a3c0c2cdf63e4276a9d843565613e40a.json"}}, {"family": "Balint", "given": "Balint Laszlo", "initials": "BL"}, {"family": "Botzki", "given": "Alexander", "initials": "A", "orcid": "0000-0001-6691-4233", "researcher": {"href": "https://publications.scilifelab.se/researcher/79448fc432054ea6af1a0c559b28567d.json"}}, {"family": "Dimec", "given": "Jure", "initials": "J", "orcid": "0000-0002-9525-9028", "researcher": {"href": "https://publications.scilifelab.se/researcher/aec05bd8a2734f6aa26fb489fce9c630.json"}}, {"family": "Dominguez Del Angel", "given": "Victoria", "initials": "V", "orcid": "0000-0002-5514-6651", "researcher": {"href": "https://publications.scilifelab.se/researcher/9a708fa6e9a44453b97cfc2089e06bec.json"}}, {"family": "Fernandes", "given": "Pedro L", "initials": "PL", "orcid": "0000-0003-2124-0241", "researcher": {"href": "https://publications.scilifelab.se/researcher/e3ca6e16ecb5403f8e344f1df671fa4a.json"}}, {"family": "Korpelainen", "given": "Eija", "initials": "E"}, {"family": "Krause", "given": "Roland", "initials": "R", "orcid": "0000-0001-9938-7126", "researcher": {"href": "https://publications.scilifelab.se/researcher/86196693e4fd402ab0493246d07d5ccb.json"}}, {"family": "Kuzak", "given": "Mateusz", "initials": "M", "orcid": "0000-0003-0087-6021", "researcher": {"href": "https://publications.scilifelab.se/researcher/821ca0fb14794a349ac838ab4a7abc1c.json"}}, {"family": "Le Pera", "given": "Loredana", "initials": "L", "orcid": "0000-0002-0076-9878", "researcher": {"href": "https://publications.scilifelab.se/researcher/0371f0fbbbbe4c0d8491e17d8aa8424a.json"}}, {"family": "Lesko\u0161ek", "given": "Brane", "initials": "B", "orcid": "0000-0001-5202-2349", "researcher": {"href": "https://publications.scilifelab.se/researcher/4d638a63af2043d2b7f8495efbd6b078.json"}}, {"family": "Lindvall", "given": "Jessica M", "initials": "JM", "orcid": "0000-0002-5042-8481", "researcher": {"href": "https://publications.scilifelab.se/researcher/78debae1bc714b11a97ecf9e9656f1eb.json"}}, {"family": "Marek", "given": "Diana", "initials": "D", "orcid": "0000-0002-9812-6351", "researcher": {"href": "https://publications.scilifelab.se/researcher/f1717147a0594eb6868f3f58a4b849e5.json"}}, {"family": "Martinez", "given": "Paula A", "initials": "PA", "orcid": "0000-0002-8990-1985", "researcher": {"href": "https://publications.scilifelab.se/researcher/25c618ae300f484bb3f589fd55eea782.json"}}, {"family": "Muyldermans", "given": "Tuur", "initials": "T", "orcid": "0000-0002-3926-7293", "researcher": {"href": "https://publications.scilifelab.se/researcher/be84fdc9e5d5439484f038bd28e0b97a.json"}}, {"family": "Nyg\u00e5rd", "given": "St\u00e5le", "initials": "S"}, {"family": "Palagi", "given": "Patricia M", "initials": "PM", "orcid": "0000-0001-9062-6303", "researcher": {"href": "https://publications.scilifelab.se/researcher/855d6f5c9a994ae49495522dfaf36281.json"}}, {"family": "Peterson", "given": "Hedi", "initials": "H", "orcid": "0000-0001-9951-5116", "researcher": {"href": "https://publications.scilifelab.se/researcher/be512162189d47059f1bd0755d6c16f8.json"}}, {"family": "Psomopoulos", "given": "Fotis", "initials": "F", "orcid": "0000-0002-0222-4273", "researcher": {"href": "https://publications.scilifelab.se/researcher/b4fd426018ab421c99e9044b31066cf9.json"}}, {"family": "Spiwok", "given": "Vojtech", "initials": "V", "orcid": "0000-0001-8108-2033", "researcher": {"href": "https://publications.scilifelab.se/researcher/1e89722bc45a4656906c79ba958cbc03.json"}}, {"family": "van Gelder", "given": "Celia W G", "initials": "CWG", "orcid": "0000-0002-0223-2329", "researcher": {"href": "https://publications.scilifelab.se/researcher/2533ac3cd3274486b5609ac643dc436b.json"}}, {"family": "Via", "given": "Allegra", "initials": "A"}, {"family": "Vidak", "given": "Marko", "initials": "M", "orcid": "0000-0001-7901-3936", "researcher": {"href": "https://publications.scilifelab.se/researcher/be1d0da74ff64f4a8ec7393577f9ba81.json"}}, {"family": "Wibberg", "given": "Daniel", "initials": "D", "orcid": "0000-0002-1331-4311", "researcher": {"href": "https://publications.scilifelab.se/researcher/771c66b20cb448e481140f476c6244ca.json"}}, {"family": "Morgan", "given": "Sarah L", "initials": "SL", "orcid": "0000-0001-9528-8323", "researcher": {"href": "https://publications.scilifelab.se/researcher/062588ade1a843ae846c4e2b96904849.json"}}, {"family": "Rustici", "given": "Gabriella", "initials": "G", "orcid": "0000-0003-3085-1271", "researcher": {"href": "https://publications.scilifelab.se/researcher/82710a270ab04a09af1550709db32b1c.json"}}], "type": "journal article", "published": "2020-07-00", "journal": {"title": "PLoS Comput. Biol.", "issn": "1553-7358", "volume": "16", "issue": "7", "pages": "e1007976", "issn-l": "1553-734X"}, "abstract": "ELIXIR is a pan-European intergovernmental organisation for life science that aims to coordinate bioinformatics resources in a single infrastructure across Europe; bioinformatics training is central to its strategy, which aims to develop a training community that spans all ELIXIR member states. In an evidence-based approach for strengthening bioinformatics training programmes across Europe, the ELIXIR Training Platform, led by the ELIXIR EXCELERATE Quality and Impact Assessment Subtask in collaboration with the ELIXIR Training Coordinators Group, has implemented an assessment strategy to measure quality and impact of its entire training portfolio. Here, we present ELIXIR's framework for assessing training quality and impact, which includes the following: specifying assessment aims, determining what data to collect in order to address these aims, and our strategy for centralised data collection to allow for ELIXIR-wide analyses. In addition, we present an overview of the ELIXIR training data collected over the past 4 years. We highlight the importance of a coordinated and consistent data collection approach and the relevance of defining specific metrics and answer scales for consortium-wide analyses as well as for comparison of data across iterations of the same course.", "doi": "10.1371/journal.pcbi.1007976", "pmid": "32702016", "labels": {"Bioinformatics Support and Infrastructure": null, "Bioinformatics Support, Infrastructure and Training": null, "Bioinformatics (NBIS)": null}, "xrefs": [{"db": "pii", "key": "PCOMPBIOL-D-19-01778"}, {"db": "pmc", "key": "PMC7377377"}], "notes": [], "created": "2020-12-15T09:16:34.028Z", "modified": "2021-11-10T12:49:57.221Z"}, {"entity": "publication", "iuid": "10d32e326ad143b48c7352913a9537b3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/10d32e326ad143b48c7352913a9537b3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/10d32e326ad143b48c7352913a9537b3"}}, "title": "A Sample Preparation Protocol for High Throughput Immunofluorescence of Suspension Cells on an Adherent Surface.", "authors": [{"family": "B\u00e4ckstr\u00f6m", "given": "Anna", "initials": "A"}, {"family": "Kugel", "given": "Laura", "initials": "L"}, {"family": "Gnann", "given": "Christian", "initials": "C"}, {"family": "Xu", "given": "Hao", "initials": "H"}, {"family": "Aslan", "given": "Joseph E", "initials": "JE"}, {"family": "Lundberg", "given": "Emma", "initials": "E", "orcid": "0000-0001-7034-0850", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ffe6259ceb540f385861b5ae52b3055.json"}}, {"family": "Stadler", "given": "Charlotte", "initials": "C", "orcid": "0000-0002-6781-1938", "researcher": {"href": "https://publications.scilifelab.se/researcher/2db3b27c7d7143cbacc8c1dd8ac90a31.json"}}], "type": "journal article", "published": "2020-07-00", "journal": {"title": "J. Histochem. Cytochem.", "issn": "1551-5044", "issn-l": "0022-1554", "volume": "68", "issue": "7", "pages": "473-489"}, "abstract": "Imaging is a powerful approach for studying protein expression and has the advantage over other methodologies in providing spatial information in situ at single cell level. Using immunofluorescence and confocal microscopy, detailed information of subcellular distribution of proteins can be obtained. While adherent cells of different tissue origin are relatively easy to prepare for imaging applications, non-adherent cells from hematopoietic origin, present a challenge due to their poor attachment to surfaces and subsequent loss of a substantial fraction of the cells. Still, these cell types represent an important part of the human proteome and express genes that are not expressed in adherent cell types. In the era of cell mapping efforts, overcoming the challenge with suspension cells for imaging applications would enable systematic profiling of hematopoietic cells. In this work, we successfully established an immunofluorescence protocol for preparation of suspension cell lines, peripheral blood mononucleated cells (PBMC) and human platelets on an adherent surface. The protocol is based on a multi-well plate format with automated sample preparation, allowing for robust high throughput imaging applications. In combination with confocal microscopy, the protocol enables systematic exploration of protein localization to all major subcellular structures.", "doi": "10.1369/0022155420935403", "pmid": "32564662", "labels": {"Spatial Proteomics": "Technology development"}, "xrefs": [{"db": "pmc", "key": "PMC7350080"}], "notes": [], "created": "2020-01-07T15:30:10.784Z", "modified": "2021-12-09T13:58:56.335Z"}, {"entity": "publication", "iuid": "aa4c5877e251458ea28d7fc3e7c01791", "links": {"self": {"href": "https://publications.scilifelab.se/publication/aa4c5877e251458ea28d7fc3e7c01791.json"}, "display": {"href": "https://publications.scilifelab.se/publication/aa4c5877e251458ea28d7fc3e7c01791"}}, "title": "High content drug screening for Fanconi anemia therapeutics.", "authors": [{"family": "Montanuy", "given": "Helena", "initials": "H"}, {"family": "Camps-Fajol", "given": "Cristina", "initials": "C"}, {"family": "Carreras-Puigvert", "given": "Jordi", "initials": "J"}, {"family": "H\u00e4ggblad", "given": "Maria", "initials": "M"}, {"family": "Lundgren", "given": "Bo", "initials": "B"}, {"family": "Aza-Carmona", "given": "Miriam", "initials": "M"}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}, {"family": "Minguill\u00f3n", "given": "Jordi", "initials": "J"}, {"family": "Surrall\u00e9s", "given": "Jordi", "initials": "J"}], "type": "journal article", "published": "2020-06-30", "journal": {"title": "Orphanet J Rare Dis", "issn": "1750-1172", "volume": "15", "issue": "1", "pages": "170", "issn-l": "1750-1172"}, "abstract": "Fanconi anemia is a rare disease clinically characterized by malformations, bone marrow failure and an increased risk of solid tumors and hematologic malignancies. The only therapies available are hematopoietic stem cell transplantation for bone marrow failure or leukemia, and surgical resection for solid tumors. Therefore, there is still an urgent need for new therapeutic options. With this aim, we developed a novel high-content cell-based screening assay to identify drugs with therapeutic potential in FA.\n\nA TALEN-mediated FANCA-deficient U2OS cell line was stably transfected with YFP-FANCD2 fusion protein. These cells were unable to form fluorescent foci or to monoubiquitinate endogenous or exogenous FANCD2 upon DNA damage and were more sensitive to mitomycin C when compared to the parental wild type counterpart. FANCA correction by retroviral infection restored the cell line's ability to form FANCD2 foci and ubiquitinate FANCD2. The feasibility of this cell-based system was interrogated in a high content screening of 3802 compounds, including a Prestwick library of 1200 FDA-approved drugs. The potential hits identified were then individually tested for their ability to rescue FANCD2 foci and monoubiquitination, and chromosomal stability in the absence of FANCA.\n\nWhile, unfortunately, none of the compounds tested were able to restore cellular FANCA-deficiency, our study shows the potential capacity to screen large compound libraries in the context of Fanconi anemia therapeutics in an optimized and cost-effective platform.", "doi": "10.1186/s13023-020-01437-1", "pmid": "32605631", "labels": {"Drug Discovery and Development": null}, "xrefs": [{"db": "pii", "key": "10.1186/s13023-020-01437-1"}, {"db": "pmc", "key": "PMC7325660"}], "notes": [], "created": "2020-12-04T14:15:05.562Z", "modified": "2025-10-17T13:05:08.012Z"}, {"entity": "publication", "iuid": "c1da6115eb61449fbd3f03367a285fc9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c1da6115eb61449fbd3f03367a285fc9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c1da6115eb61449fbd3f03367a285fc9"}}, "title": "Genome assembly of the basket willow, Salix viminalis, reveals earliest stages of sex chromosome expansion.", "authors": [{"family": "Almeida", "given": "Pedro", "initials": "P", "orcid": "0000-0001-6790-8687", "researcher": {"href": "https://publications.scilifelab.se/researcher/bb2e2881fe7449659d89e9beb407e0a4.json"}}, {"family": "Proux-Wera", "given": "Estelle", "initials": "E"}, {"family": "Churcher", "given": "Allison", "initials": "A"}, {"family": "Soler", "given": "Lucile", "initials": "L"}, {"family": "Dainat", "given": "Jacques", "initials": "J"}, {"family": "Pucholt", "given": "Pascal", "initials": "P"}, {"family": "Nordlund", "given": "Jessica", "initials": "J", "orcid": "0000-0001-8699-9959", "researcher": {"href": "https://publications.scilifelab.se/researcher/ddf48c9262134821bcc6ce1180049753.json"}}, {"family": "Martin", "given": "Tom", "initials": "T"}, {"family": "R\u00f6nnberg-W\u00e4stljung", "given": "Ann-Christin", "initials": "AC"}, {"family": "Nystedt", "given": "Bj\u00f6rn", "initials": "B", "orcid": "0000-0001-7809-7664", "researcher": {"href": "https://publications.scilifelab.se/researcher/f0af5a168baa4b00a6fab8d3447ebfb4.json"}}, {"family": "Berlin", "given": "Sofia", "initials": "S"}, {"family": "Mank", "given": "Judith E", "initials": "JE"}], "type": "journal article", "published": "2020-06-30", "journal": {"title": "BMC Biol.", "issn": "1741-7007", "issn-l": "1741-7007", "volume": "18", "issue": "1", "pages": "78"}, "abstract": "Sex chromosomes have evolved independently multiple times in eukaryotes and are therefore considered a prime example of convergent genome evolution. Sex chromosomes are known to emerge after recombination is halted between a homologous pair of chromosomes, and this leads to a range of non-adaptive modifications causing gradual degeneration and gene loss on the sex-limited chromosome. However, the proximal causes of recombination suppression and the pace at which degeneration subsequently occurs remain unclear.\n\nHere, we use long- and short-read single-molecule sequencing approaches to assemble and annotate a draft genome of the basket willow, Salix viminalis, a species with a female heterogametic system at the earliest stages of sex chromosome emergence. Our single-molecule approach allowed us to phase the emerging Z and W haplotypes in a female, and we detected very low levels of Z/W single-nucleotide divergence in the non-recombining region. Linked-read sequencing of the same female and an additional male (ZZ) revealed the presence of two evolutionary strata supported by both divergence between the Z and W haplotypes and by haplotype phylogenetic trees. Gene order is still largely conserved between the Z and W homologs, although the W-linked region contains genes involved in cytokinin signaling regulation that are not syntenic with the Z homolog. Furthermore, we find no support across multiple lines of evidence for inversions, which have long been assumed to halt recombination between the sex chromosomes.\n\nOur data suggest that selection against recombination is a more gradual process at the earliest stages of sex chromosome formation than would be expected from an inversion and may result instead from the accumulation of transposable elements. Our results present a cohesive understanding of the earliest genomic consequences of recombination suppression as well as valuable insights into the initial stages of sex chromosome formation and regulation of sex differentiation.", "doi": "10.1186/s12915-020-00808-1", "pmid": "32605573", "labels": {"National Genomics Infrastructure": "Collaborative", "NGI Uppsala (SNP&SEQ Technology Platform)": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1186/s12915-020-00808-1"}, {"db": "pmc", "key": "PMC7329446"}], "notes": [], "created": "2020-07-03T05:25:52.141Z", "modified": "2021-11-10T12:50:00.669Z"}, {"entity": "publication", "iuid": "194d913bd2654246bcdf9732ca06b6e2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/194d913bd2654246bcdf9732ca06b6e2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/194d913bd2654246bcdf9732ca06b6e2"}}, "title": "An efficient single-cell transcriptomics workflow for microbial eukaryotes benchmarked on Giardia intestinalis cells.", "authors": [{"family": "Onsbring", "given": "Henning", "initials": "H"}, {"family": "Tice", "given": "Alexander K", "initials": "AK"}, {"family": "Barton", "given": "Brandon T", "initials": "BT"}, {"family": "Brown", "given": "Matthew W", "initials": "MW"}, {"family": "Ettema", "given": "Thijs J G", "initials": "TJG", "orcid": "0000-0002-6898-6377", "researcher": {"href": "https://publications.scilifelab.se/researcher/42fc4acc111f4c488b23fa41341705e2.json"}}], "type": "journal article", "published": "2020-06-29", "journal": {"title": "BMC Genomics", "issn": "1471-2164", "volume": "21", "issue": "1", "pages": "448", "issn-l": "1471-2164"}, "abstract": "Most diversity in the eukaryotic tree of life is represented by microbial eukaryotes, which is a polyphyletic group also referred to as protists. Among the protists, currently sequenced genomes and transcriptomes give a biased view of the actual diversity. This biased view is partly caused by the scientific community, which has prioritized certain microbes of biomedical and agricultural importance. Additionally, some protists remain difficult to maintain in cultures, which further influences what has been studied. It is now possible to bypass the time-consuming process of cultivation and directly analyze the gene content of single protist cells. Single-cell genomics was used in the first experiments where individual protists cells were genomically explored. Unfortunately, single-cell genomics for protists is often associated with low genome recovery and the assembly process can be complicated because of repetitive intergenic regions. Sequencing repetitive sequences can be avoided if single-cell transcriptomics is used, which only targets the part of the genome that is transcribed.\n\nIn this study we test different modifications of Smart-seq2, a single-cell RNA sequencing protocol originally developed for mammalian cells, to establish a robust and more cost-efficient workflow for protists. The diplomonad Giardia intestinalis was used in all experiments and the available genome for this species allowed us to benchmark our results. We could observe increased transcript recovery when freeze-thaw cycles were added as an extra step to the Smart-seq2 protocol. Further we reduced the reaction volume and purified the amplified cDNA with alternative beads to test different cost-reducing changes of Smart-seq2. Neither improved the procedure, and reducing the volumes by half led to significantly fewer genes detected. We also added a 5' biotin modification to our primers and reduced the concentration of oligo-dT, to potentially reduce generation of artifacts. Except adding freeze-thaw cycles and reducing the volume, no other modifications lead to a significant change in gene detection. Therefore, we suggest adding freeze-thaw cycles to Smart-seq2 when working with protists and further consider our other modification described to improve cost and time-efficiency.\n\nThe presented single-cell RNA sequencing workflow represents an efficient method to explore the diversity and cell biology of individual protist cells.", "doi": "10.1186/s12864-020-06858-7", "pmid": "32600266", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Microbial Single Cell Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12864-020-06858-7"}, {"db": "pmc", "key": "PMC7325058"}], "notes": [], "created": "2020-07-03T05:25:51.570Z", "modified": "2021-11-10T12:44:49.955Z"}, {"entity": "publication", "iuid": "3f9436baa42849ed95e219bbf949416e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3f9436baa42849ed95e219bbf949416e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3f9436baa42849ed95e219bbf949416e"}}, "title": "Whole genome sequencing of familial isolated oesophagus atresia uncover shared structural variants.", "authors": [{"family": "Klar", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4185-7409", "researcher": {"href": "https://publications.scilifelab.se/researcher/3310cb2ab70f43d78cc7cd7e36ac8f83.json"}}, {"family": "Engstrand-Lilja", "given": "Helene", "initials": "H"}, {"family": "Maqbool", "given": "Khurram", "initials": "K"}, {"family": "Mattisson", "given": "Jonas", "initials": "J"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}, {"family": "Dahl", "given": "Niklas", "initials": "N"}], "type": "journal article", "published": "2020-06-26", "journal": {"title": "BMC Med Genomics", "issn": "1755-8794", "volume": "13", "issue": "1", "pages": "85", "issn-l": "1755-8794"}, "abstract": "Oesophageal atresia (OA) is a life-threatening developmental defect characterized by a lost continuity between the upper and lower oesophagus. The most common form is a distal connection between the trachea and the oesophagus, i.e. a tracheoesophageal fistula (TEF). The condition may be part of a syndrome or occurs as an isolated feature. The recurrence risk in affected families is increased compared to the population-based incidence suggesting contributing genetic factors.\n\nTo gain insight into gene variants and genes associated with isolated OA we conducted whole genome sequencing on samples from three families with recurrent cases affected by congenital and isolated TEF.\n\nWe identified a combination of single nucleotide variants (SNVs), splice site variants (SSV) and structural variants (SV) annotated to altogether 100 coding genes in the six affected individuals.\n\nThis study highlights rare SVs among candidate gene variants in our individuals with OA and provides a gene framework for further investigations of genetic factors behind this malformation.", "doi": "10.1186/s12920-020-00737-6", "pmid": "32586322", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12920-020-00737-6"}, {"db": "pmc", "key": "PMC7318369"}], "notes": [], "created": "2020-07-03T05:25:29.915Z", "modified": "2024-01-16T13:48:42.333Z"}, {"entity": "publication", "iuid": "0b15b32dffe24e6c9ddd62c29e602101", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0b15b32dffe24e6c9ddd62c29e602101.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0b15b32dffe24e6c9ddd62c29e602101"}}, "title": "Evolutionary History of the Marchantia polymorpha Complex.", "authors": [{"family": "Linde", "given": "Anna-Malin", "initials": "AM"}, {"family": "Sawangproh", "given": "Weerachon", "initials": "W"}, {"family": "Cronberg", "given": "Nils", "initials": "N"}, {"family": "Sz\u00f6v\u00e9nyi", "given": "P\u00e9ter", "initials": "P"}, {"family": "Lagercrantz", "given": "Ulf", "initials": "U"}], "type": "journal article", "published": "2020-06-26", "journal": {"title": "Front Plant Sci", "issn": "1664-462X", "volume": "11", "issue": null, "pages": "829", "issn-l": "1664-462X"}, "abstract": "The potential role of introgression in evolution has gained increased interest in recent years. Although some fascinating examples have been reported, more information is needed to generalize the importance of hybridization and introgression for adaptive divergence. As limited data exist on haploid dominant species, we analyzed genomes of three subspecies of the liverwort Marchantia polymorpha. We used available genomic data for subsp. ruderalis and carried out whole-genome (PacBio) sequencing for one individual each of subsp. montivagans and subsp. polymorpha as well as Illumina resequencing of additional genomes for all three subspecies. The three subspecies were compared against M. paleacea as outgroup. Our analyses revealed separation of the three taxa, but all three possible topologies were richly represented across the genomes, and the underlying divergence order less obvious. This uncertainty could be the result of the divergence of the three subspecies close in time, or that introgression has been frequent since divergence. In particular, we found that pseudo-chromosome 2 in subsp. montivagans was much more diverged than other parts of the genomes. This could either be explained by specific capture of chromosome 2 from an unknown related species through hybridization or by conservation of chromosome 2 despite intermittent or ongoing introgression affecting more permeable parts of the genomes. A higher degree of chromosomal rearrangements on pseudo-chromosome 2 support the second hypothesis. Species tree analyses recovered an overall topology where subsp. montivagans diverged first and subsp. ruderalis and subsp. polymorpha appeared as sister lineages. Each subspecies was associated with its own chloroplast and mitochondrial haplotype group. Our data suggest introgression but refute a previous hypothesis that subsp. ruderalis is a new stabilized hybrid between the other two subspecies.", "doi": "10.3389/fpls.2020.00829", "pmid": "32670318", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7332582"}], "notes": [], "created": "2020-08-25T13:05:18.846Z", "modified": "2024-01-16T13:48:42.341Z"}, {"entity": "publication", "iuid": "d44fd9d44752484f996cf097d055c88b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d44fd9d44752484f996cf097d055c88b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d44fd9d44752484f996cf097d055c88b"}}, "title": "CAM-Delam: an in vivo approach to visualize and quantify the delamination and invasion capacity of human cancer cells.", "authors": [{"family": "Palaniappan", "given": "Tamilarasan K", "initials": "TK"}, {"family": "\u0160lekien\u0117", "given": "Lina", "initials": "L"}, {"family": "Jonasson", "given": "Anna-Karin", "initials": "AK"}, {"family": "Gilthorpe", "given": "Jonathan", "initials": "J"}, {"family": "Gunhaga", "given": "Lena", "initials": "L"}], "type": "journal article", "published": "2020-06-26", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "10472", "issn-l": "2045-2322"}, "abstract": "The development of metastases is the major cause of cancer related death. To develop a standardized method that define the ability of human cancer cells to degrade the basement membrane, e.g. the delamination capacity, is of importance to assess metastatic aggressiveness. We now present the in vivo CAM-Delam assay to visualize and quantify the ability of human cancer cells to delaminate and invade. The method includes seeding cancer cells on the chick chorioallantoic membrane (CAM), followed by the evaluation of cancer-induced delamination and potential invasion within hours to a few days. By testing a range of human cancer cell lines in the CAM-Delam assay, our results show that the delamination capacity can be divided into four categories and used to quantify metastatic aggressiveness. Our results emphasize the usefulness of this assay for quantifying delamination capacity as a measurement of metastatic aggressiveness, and in unraveling the molecular mechanisms that regulate delamination, invasion, formation of micro-metastases and modulations of the tumor microenvironment. This method will be useful in both the preclinical and clinical characterization of tumor biopsies, and in the validation of compounds that may improve survival in metastatic cancer.", "doi": "10.1038/s41598-020-67492-7", "pmid": "32591581", "labels": {"NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-67492-7"}, {"db": "pmc", "key": "PMC7320147"}], "notes": [], "created": "2021-12-06T13:45:24.619Z", "modified": "2021-12-06T13:45:24.635Z"}, {"entity": "publication", "iuid": "ad6c085540e747d5ac95fbe1622c8b7d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ad6c085540e747d5ac95fbe1622c8b7d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ad6c085540e747d5ac95fbe1622c8b7d"}}, "title": "RNA-seq reveals altered gene expression levels in proximal tubular cell cultures compared to renal cortex but not during early glucotoxicity.", "authors": [{"family": "Nilsson", "given": "Linn\u00e9a M", "initials": "LM"}, {"family": "Castresana-Aguirre", "given": "Miguel", "initials": "M", "orcid": "0000-0002-4665-6537", "researcher": {"href": "https://publications.scilifelab.se/researcher/df8394cb200743c4b13ee549bfe8492b.json"}}, {"family": "Scott", "given": "Lena", "initials": "L"}, {"family": "Brismar", "given": "Hjalmar", "initials": "H", "orcid": "0000-0003-0578-4003", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ec23336e2ef4e298f340876f1136dce.json"}}], "type": "journal article", "published": "2020-06-25", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "10390", "issn-l": "2045-2322"}, "abstract": "Cell cultures are often used to study physiological processes in health and disease. It is well-known that cells change their gene expression in vitro compared to in vivo, but it is rarely experimentally addressed. High glucose is a known trigger of apoptosis in proximal tubular cells (PTC). Here we used RNA-seq to detect differentially expressed genes in cultures of primary rat PTC, 3 days old, compared to cells retrieved directly from rat outer renal cortex and between PTC exposed to 15 mM glucose and control for 8 h. The expression of 6,174 genes was significantly up- or downregulated in the cultures of PTC compared to the cells in the outer renal cortex. Most altered were mitochondrial and metabolism related genes. Gene expression of proapoptotic proteins were upregulated and gene expression of antiapoptotic proteins were downregulated in PTC. Expression of transporter related genes were generally downregulated. After 8 h, high glucose had not altered the gene expression in PTC. The current study provides evidence that cells alter their gene expression in vitro compared to in vivo and suggests that short-term high glucose exposure can trigger apoptosis in PTC without changing the gene expression levels of apoptotic proteins.", "doi": "10.1038/s41598-020-67361-3", "pmid": "32587318", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-67361-3"}, {"db": "pmc", "key": "PMC7316724"}], "notes": [], "created": "2020-12-07T16:27:02.399Z", "modified": "2021-11-10T12:50:06.705Z"}, {"entity": "publication", "iuid": "1472dc974e934876920eaee93787c313", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1472dc974e934876920eaee93787c313.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1472dc974e934876920eaee93787c313"}}, "title": "A site-specific self-assembled light-up rotor probe for selective recognition and stabilization of c-MYC G-quadruplex DNA.", "authors": [{"family": "Deiana", "given": "Marco", "initials": "M", "orcid": "0000-0002-7815-4494", "researcher": {"href": "https://publications.scilifelab.se/researcher/f9efbe74ca3940029d782d3ba645fa34.json"}}, {"family": "Chand", "given": "Karam", "initials": "K", "orcid": "0000-0001-7691-4392", "researcher": {"href": "https://publications.scilifelab.se/researcher/a20b7a82f4444b92b3ac1897e2fdb790.json"}}, {"family": "Jamroskovic", "given": "Jan", "initials": "J", "orcid": "0000-0001-6871-7663", "researcher": {"href": "https://publications.scilifelab.se/researcher/154847e2f84f4336a07e219fac6db2f9.json"}}, {"family": "Das", "given": "Rabindra Nath", "initials": "RN", "orcid": "0000-0001-6347-2169", "researcher": {"href": "https://publications.scilifelab.se/researcher/fec8d8bcbe8648258cfbab86693c77c6.json"}}, {"family": "Obi", "given": "Ikenna", "initials": "I", "orcid": "0000-0003-0364-8964", "researcher": {"href": "https://publications.scilifelab.se/researcher/e46c65e7b0e540b0a7c225d54c1502d7.json"}}, {"family": "Chorell", "given": "Erik", "initials": "E", "orcid": "0000-0003-2523-1940", "researcher": {"href": "https://publications.scilifelab.se/researcher/ada783ae0a824621a3b8e1024aae13a4.json"}}, {"family": "Sabouri", "given": "Nasim", "initials": "N", "orcid": "0000-0002-4541-7702", "researcher": {"href": "https://publications.scilifelab.se/researcher/4bdc688dc85a4932acfdfffad8bfc443.json"}}], "type": "journal article", "published": "2020-06-25", "journal": {"title": "Nanoscale", "issn": "2040-3372", "volume": "12", "issue": "24", "pages": "12950-12957", "issn-l": "2040-3364"}, "abstract": "Direct and unambiguous evidence of the formation of G-quadruplexes (G4s) in human cells have shown their implication in several key biological events and has emphasized their role as important targets for small-molecule cancer therapeutics. Here, we report on the first example of a self-assembled molecular-rotor G4-binder able to discriminate between an extensive panel of G4 and non-G4 structures and to selectively light-up (up to 64-fold), bind (nanomolar range), and stabilize the c-MYC promoter G4 DNA. In particular, association with the c-MYC G4 triggers the disassembly of its supramolecular state (disaggregation-induced emission, DIE) and induces geometrical restrictions (motion-induced change in emission, MICE) leading to a significant enhancement of its emission yield. Moreover, this optical reporter is able to selectively stabilize the c-MYC G4 and inhibit DNA synthesis. Finally, by using confocal laser-scanning microscopy (CLSM) we show the ability of this compound to localize primarily in the subnuclear G4-rich compartments of cancer cells. This work provides a benchmark for the future design and development of a new generation of smart sequence-selective supramolecular G4-binders that combine outstanding sensing and stability properties, to be utilized in anti-cancer therapy.", "doi": "10.1039/d0nr03404e", "pmid": "32525170", "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [], "notes": [], "created": "2020-11-24T20:27:45.025Z", "modified": "2025-10-17T13:03:56.850Z"}, {"entity": "publication", "iuid": "870f001b1e924bc3b362c4ae5d683273", "links": {"self": {"href": "https://publications.scilifelab.se/publication/870f001b1e924bc3b362c4ae5d683273.json"}, "display": {"href": "https://publications.scilifelab.se/publication/870f001b1e924bc3b362c4ae5d683273"}}, "title": "Whole-genome sequence association analysis of blood proteins in a longitudinal wellness cohort.", "authors": [{"family": "Zhong", "given": "Wen", "initials": "W"}, {"family": "Gummesson", "given": "Anders", "initials": "A"}, {"family": "Tebani", "given": "Abdellah", "initials": "A"}, {"family": "Karlsson", "given": "Max J", "initials": "MJ"}, {"family": "Hong", "given": "Mun-Gwan", "initials": "MG"}, {"family": "Schwenk", "given": "Jochen M", "initials": "JM", "orcid": "0000-0001-8141-8449", "researcher": {"href": "https://publications.scilifelab.se/researcher/aba5822711b246b397fffacb7ae403b3.json"}}, {"family": "Edfors", "given": "Fredrik", "initials": "F"}, {"family": "Bergstr\u00f6m", "given": "G\u00f6ran", "initials": "G"}, {"family": "Fagerberg", "given": "Linn", "initials": "L"}, {"family": "Uhl\u00e9n", "given": "Mathias", "initials": "M", "orcid": "0000-0002-4858-8056", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff81da3cb0cf4262873b993a1b06798c.json"}}], "type": "journal article", "published": "2020-06-23", "journal": {"title": "Genome Med", "issn": "1756-994X", "issn-l": "1756-994X", "volume": "12", "issue": "1", "pages": "53"}, "abstract": "The human plasma proteome is important for many biological processes and targets for diagnostics and therapy. It is therefore of great interest to understand the interplay of genetic and environmental factors to determine the specific protein levels in individuals and to gain a deeper insight of the importance of genetic architecture related to the individual variability of plasma levels of proteins during adult life.\n\nWe have combined whole-genome sequencing, multiplex plasma protein profiling, and extensive clinical phenotyping in a longitudinal 2-year wellness study of 101 healthy individuals with repeated sampling. Analyses of genetic and non-genetic associations related to the variability of blood levels of proteins in these individuals were performed.\n\nThe analyses showed that each individual has a unique protein profile, and we report on the intra-individual as well as inter-individual variation for 794 plasma proteins. A genome-wide association study (GWAS) using 7.3 million genetic variants identified by whole-genome sequencing revealed 144 independent variants across 107 proteins that showed strong association (P < 6 \u00d7 10-11) between genetics and the inter-individual variability on protein levels. Many proteins not reported before were identified (67 out of 107) with individual plasma level affected by genetics. Our longitudinal analysis further demonstrates that these levels are stable during the 2-year study period. The variability of protein profiles as a consequence of environmental factors was also analyzed with focus on the effects of weight loss and infections.\n\nWe show that the adult blood levels of many proteins are determined at birth by genetics, which is important for efforts aimed to understand the relationship between plasma proteome profiles and human biology and disease.", "doi": "10.1186/s13073-020-00755-0", "pmid": "32576278", "labels": {"Affinity Proteomics Stockholm": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s13073-020-00755-0"}, {"db": "pmc", "key": "PMC7310558"}], "notes": [], "created": "2020-12-10T19:03:45.805Z", "modified": "2024-01-16T13:48:42.348Z"}, {"entity": "publication", "iuid": "8b45074cc63c44b38845bd3e64899cdb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8b45074cc63c44b38845bd3e64899cdb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8b45074cc63c44b38845bd3e64899cdb"}}, "title": "Skeletal Muscle Transcriptomic Comparison between Long-Term Trained and Untrained Men and Women.", "authors": [{"family": "Chapman", "given": "Mark A", "initials": "MA", "orcid": "0000-0001-9905-4022", "researcher": {"href": "https://publications.scilifelab.se/researcher/1fe649290e7b44079be880b52ea8fe98.json"}}, {"family": "Arif", "given": "Muhammad", "initials": "M"}, {"family": "Emanuelsson", "given": "Eric B", "initials": "EB"}, {"family": "Reitzner", "given": "Stefan M", "initials": "SM"}, {"family": "Lindholm", "given": "Mal\u00e9ne E", "initials": "ME"}, {"family": "Mardinoglu", "given": "Adil", "initials": "A"}, {"family": "Sundberg", "given": "Carl Johan", "initials": "CJ"}], "type": "comparative study", "published": "2020-06-23", "journal": {"title": "Cell Rep", "issn": "2211-1247", "volume": "31", "issue": "12", "pages": "107808", "issn-l": null}, "abstract": "To better understand the health benefits of lifelong exercise in humans, we conduct global skeletal muscle transcriptomic analyses of long-term endurance- (9 men, 9 women) and strength-trained (7 men) humans compared with age-matched untrained controls (7 men, 8 women). Transcriptomic analysis, Gene Ontology, and genome-scale metabolic modeling demonstrate changes in pathways related to the prevention of metabolic diseases, particularly with endurance training. Our data also show prominent sex differences between controls and that these differences are reduced with endurance training. Additionally, we compare our data with studies examining muscle gene expression before and after a months-long training period in individuals with metabolic diseases. This analysis reveals that training shifts gene expression in individuals with impaired metabolism to become more similar to our endurance-trained group. Overall, our data provide an extensive examination of the accumulated transcriptional changes that occur with decades-long training and identify important \"exercise-responsive\" genes that could attenuate metabolic disease.", "doi": "10.1016/j.celrep.2020.107808", "pmid": "32579934", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S2211-1247(20)30789-0"}], "notes": [], "created": "2020-07-08T13:04:34.799Z", "modified": "2024-01-16T13:48:42.357Z"}, {"entity": "publication", "iuid": "ee18a396f79f4e90a668a1318fc73ed8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ee18a396f79f4e90a668a1318fc73ed8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ee18a396f79f4e90a668a1318fc73ed8"}}, "title": "Amyloid precursor protein-b facilitates cell adhesion during early development in zebrafish.", "authors": [{"family": "Banote", "given": "Rakesh Kumar", "initials": "RK"}, {"family": "Chebli", "given": "Jasmine", "initials": "J"}, {"family": "\u015eat\u0131r", "given": "Tu\u011f\u00e7e Munise", "initials": "TM"}, {"family": "Varshney", "given": "Gaurav K", "initials": "GK", "orcid": "0000-0002-0429-1904", "researcher": {"href": "https://publications.scilifelab.se/researcher/a5b107029a9844de8b103873831b54f2.json"}}, {"family": "Camacho", "given": "Rafael", "initials": "R", "orcid": "0000-0003-2325-6407", "researcher": {"href": "https://publications.scilifelab.se/researcher/6a7a8cfe28634821984b078ce3246343.json"}}, {"family": "Ledin", "given": "Johan", "initials": "J", "orcid": "0000-0002-7319-7735", "researcher": {"href": "https://publications.scilifelab.se/researcher/92e482abc18c49d881d3bf0132b3fbcd.json"}}, {"family": "Burgess", "given": "Shawn M", "initials": "SM", "orcid": "0000-0003-1147-0596", "researcher": {"href": "https://publications.scilifelab.se/researcher/bf85532f49bc4208b7e456d4ee2e8f76.json"}}, {"family": "Abramsson", "given": "Alexandra", "initials": "A", "orcid": "0000-0002-4715-9225", "researcher": {"href": "https://publications.scilifelab.se/researcher/7abde12dab2e4d338bc6e55933f07531.json"}}, {"family": "Zetterberg", "given": "Henrik", "initials": "H"}], "type": "journal article", "published": "2020-06-23", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "10127", "issn-l": "2045-2322"}, "abstract": "Understanding the biological function of amyloid beta (A\u03b2) precursor protein (APP) beyond its role in Alzheimer's disease is emerging. Yet, its function during embryonic development is poorly understood. The zebrafish APP orthologue, Appb, is strongly expressed during early development but thus far has only been studied via morpholino-mediated knockdown. Zebrafish enables analysis of cellular processes in an ontogenic context, which is limited in many other vertebrates. We characterized zebrafish carrying a homozygous mutation that introduces a premature stop in exon 2 of the appb gene. We report that appb mutants are significantly smaller until 2 dpf and display perturbed enveloping layer (EVL) integrity and cell protrusions at the blastula stage. Moreover, appb mutants surviving beyond 48 hpf exhibited no behavioral defects at 6 dpf and developed into healthy and fertile adults. The expression of the app family member, appa, was also found to be altered in appb mutants. Taken together, we show that appb is involved in the initial development of zebrafish by supporting the integrity of the EVL, likely by mediating cell adhesion properties. The loss of Appb might then be compensated for by other app family members to maintain normal development.", "doi": "10.1038/s41598-020-66584-8", "pmid": "32576936", "labels": {"Genome Engineering Zebrafish": "Collaborative", "Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7311384"}, {"db": "pii", "key": "10.1038/s41598-020-66584-8"}], "notes": [], "created": "2020-06-24T09:03:55.674Z", "modified": "2023-02-16T08:03:52.996Z"}, {"entity": "publication", "iuid": "d64c9f1bb86044c88061329283767e2e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d64c9f1bb86044c88061329283767e2e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d64c9f1bb86044c88061329283767e2e"}}, "title": "Altered levels of CSF proteins in patients with FTD, presymptomatic mutation carriers and non-carriers.", "authors": [{"family": "Remnest\u00e5l", "given": "Julia", "initials": "J", "orcid": "0000-0002-3908-6476", "researcher": {"href": "https://publications.scilifelab.se/researcher/00a88350afba45fb8200786904bf51ca.json"}}, {"family": "\u00d6ijerstedt", "given": "Linn", "initials": "L"}, {"family": "Ullgren", "given": "Abbe", "initials": "A"}, {"family": "Olofsson", "given": "Jennie", "initials": "J"}, {"family": "Bergstr\u00f6m", "given": "Sofia", "initials": "S"}, {"family": "Kultima", "given": "Kim", "initials": "K"}, {"family": "Ingelsson", "given": "Martin", "initials": "M"}, {"family": "Kilander", "given": "Lena", "initials": "L"}, {"family": "Uhl\u00e9n", "given": "Mathias", "initials": "M", "orcid": "0000-0002-4858-8056", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff81da3cb0cf4262873b993a1b06798c.json"}}, {"family": "M\u00e5nberg", "given": "Anna", "initials": "A"}, {"family": "Graff", "given": "Caroline", "initials": "C"}, {"family": "Nilsson", "given": "Peter", "initials": "P", "orcid": "0000-0002-4657-8532", "researcher": {"href": "https://publications.scilifelab.se/researcher/799bcf1cf8cf451296f4535dd4ca9dc0.json"}}], "type": "journal article", "published": "2020-06-23", "journal": {"title": "Transl Neurodegener", "issn": "2047-9158", "volume": "9", "issue": "1", "pages": "27", "issn-l": null}, "abstract": "The clinical presentations of frontotemporal dementia (FTD) are diverse and overlap with other neurological disorders. There are, as of today, no biomarkers in clinical practice for diagnosing the disorders. Here, we aimed to find protein markers in cerebrospinal fluid (CSF) from patients with FTD, presymptomatic mutation carriers and non-carriers.\n\nAntibody suspension bead arrays were used to analyse 328 proteins in CSF from patients with behavioural variant FTD (bvFTD, n = 16) and progressive primary aphasia (PPA, n = 13), as well as presymptomatic mutation carriers (PMC, n = 16) and non-carriers (NC, n = 8). A total of 492 antibodies were used to measure protein levels by direct labelling of the CSF samples. The findings were further examined in an independent cohort including 13 FTD patients, 79 patients with Alzheimer's disease and 18 healthy controls.\n\nWe found significantly altered protein levels in CSF from FTD patients compared to unaffected individuals (PMC and NC) for 26 proteins. The analysis show patterns of separation between unaffected individuals and FTD patients, especially for those with a clinical diagnosis of bvFTD. The most statistically significant differences in protein levels were found for VGF, TN-R, NPTXR, TMEM132D, PDYN and NF-M. Patients with FTD were found to have higher levels of TN-R and NF-M, and lower levels of VGF, NPTXR, TMEM132D and PDYN, compared to unaffected individuals. The main findings were reproduced in the independent cohort.\n\nIn this pilot study, we show a separation of FTD patients from unaffected individuals based on protein levels in CSF. Further investigation is required to explore the CSF profiles in larger cohorts, but the results presented here has the potential to enable future clinical utilization of these potential biomarkers within FTD.", "doi": "10.1186/s40035-020-00198-y", "pmid": "32576262", "labels": {"NGI Stockholm (Genomics Applications)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s40035-020-00198-y"}, {"db": "pmc", "key": "PMC7310563"}], "notes": [], "created": "2021-01-08T16:29:12.262Z", "modified": "2024-01-16T13:48:42.365Z"}, {"entity": "publication", "iuid": "6c8aeba1616344878cd935afa0266f3d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6c8aeba1616344878cd935afa0266f3d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6c8aeba1616344878cd935afa0266f3d"}}, "title": "Decreased detection of ESBL- or pAmpC-producing Escherichia coli in broiler breeders imported into Sweden.", "authors": [{"family": "Nilsson", "given": "Oskar", "initials": "O"}, {"family": "B\u00f6rjesson", "given": "Stefan", "initials": "S", "orcid": "0000-0003-2219-2659", "researcher": {"href": "https://publications.scilifelab.se/researcher/e98c1d640f9a4eeaba4563eeec9e7dff.json"}}, {"family": "Land\u00e9n", "given": "Annica", "initials": "A"}, {"family": "Greko", "given": "Christina", "initials": "C"}, {"family": "Bengtsson", "given": "Bj\u00f6rn", "initials": "B"}], "type": "journal article", "published": "2020-06-22", "journal": {"title": "Acta Vet. Scand.", "issn": "1751-0147", "volume": "62", "issue": "1", "pages": "33", "issn-l": "0044-605X"}, "abstract": "In the spring of 2010, it was discovered that a large proportion of broilers in Sweden were colonized with Escherichia coli producing extended-spectrum beta-lactamases (ESBL) or plasmid mediated AmpC (pAmpC). It was hypothesized that the high prevalence was due to transfer from an upper level in the production pyramid and sampling upwards in the production pyramid was initiated. From 2010 to 2019, all shipments (n = 122) of broiler breeders were screened on arrival to Sweden for the occurrence of ESBL- or pAmpC-producing E. coli using selective methods. Samples of paper linings from shipments of breeders were cultured on MacConkey agar supplemented with cefotaxime (1 mg/L) after pre-enrichment in either MacConkey broth with cefotaxime (1 mg/L), or from late June 2015 in buffered peptone water without antibiotics. ESBL- or pAmpC-producing E. coli was isolated from 43 (35%) of these. Over the years, the proportion of positive imports have decreased and during 2018 and 2019 all imports were negative. In conclusion, the occurrence of ESBL- or pAmpC-producing E. coli in broiler breeders on arrival to Sweden has decreased. Such bacteria have not been detected in any shipments since 2017.", "doi": "10.1186/s13028-020-00532-4", "pmid": "32571370", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s13028-020-00532-4"}, {"db": "pmc", "key": "PMC7310155"}], "notes": [], "created": "2021-12-10T15:40:02.136Z", "modified": "2021-12-10T15:40:34.724Z"}, {"entity": "publication", "iuid": "13c41a768f9148d9956c1d62ccfeba4c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/13c41a768f9148d9956c1d62ccfeba4c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/13c41a768f9148d9956c1d62ccfeba4c"}}, "title": "Accelerated Nuclear Magnetic Resonance Spectroscopy with Deep Learning.", "authors": [{"family": "Qu", "given": "Xiaobo", "initials": "X", "orcid": "0000-0002-8675-5820", "researcher": {"href": "https://publications.scilifelab.se/researcher/cd0bbb61a58d4218ac29f5ec08ed3520.json"}}, {"family": "Huang", "given": "Yihui", "initials": "Y"}, {"family": "Lu", "given": "Hengfa", "initials": "H"}, {"family": "Qiu", "given": "Tianyu", "initials": "T"}, {"family": "Guo", "given": "Di", "initials": "D"}, {"family": "Agback", "given": "Tatiana", "initials": "T"}, {"family": "Orekhov", "given": "Vladislav", "initials": "V"}, {"family": "Chen", "given": "Zhong", "initials": "Z"}], "type": "journal article", "published": "2020-06-22", "journal": {"title": "Angew. Chem. Int. Ed. Engl.", "issn": "1521-3773", "volume": "59", "issue": "26", "pages": "10297-10300", "issn-l": "1433-7851"}, "abstract": "Nuclear magnetic resonance (NMR) spectroscopy serves as an indispensable tool in chemistry and biology but often suffers from long experimental times. We present a proof-of-concept of the application of deep learning and neural networks for high-quality, reliable, and very fast NMR spectra reconstruction from limited experimental data. We show that the neural network training can be achieved using solely synthetic NMR signals, which lifts the prohibiting demand for a large volume of realistic training data usually required for a deep learning approach.", "doi": "10.1002/anie.201908162", "pmid": "31490596", "labels": {"Swedish NMR Centre": "Collaborative"}, "xrefs": [], "notes": [], "created": "2023-05-31T16:46:28.376Z", "modified": "2025-10-17T13:03:56.883Z"}, {"entity": "publication", "iuid": "0006dd06fdae4e958b22569ce4577e4e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0006dd06fdae4e958b22569ce4577e4e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0006dd06fdae4e958b22569ce4577e4e"}}, "title": "T2 and T17 cytokines alter the cargo and function of airway epithelium-derived extracellular vesicles.", "authors": [{"family": "Ax", "given": "Elisabeth", "initials": "E", "orcid": "0000-0001-7553-5059", "researcher": {"href": "https://publications.scilifelab.se/researcher/3c2961415fa942a2b18c7272da4d91e4.json"}}, {"family": "Jevnikar", "given": "Zala", "initials": "Z"}, {"family": "Cvjetkovic", "given": "Aleksander", "initials": "A", "orcid": "0000-0002-9131-9791", "researcher": {"href": "https://publications.scilifelab.se/researcher/166451e5c8e54c0da297f6238c42c334.json"}}, {"family": "Malmh\u00e4ll", "given": "Carina", "initials": "C", "orcid": "0000-0001-6696-7570", "researcher": {"href": "https://publications.scilifelab.se/researcher/11c1a836d6d64df78e044403f9cc01db.json"}}, {"family": "Olsson", "given": "Henric", "initials": "H"}, {"family": "R\u00e5dinger", "given": "Madeleine", "initials": "M", "orcid": "0000-0002-0652-7378", "researcher": {"href": "https://publications.scilifelab.se/researcher/f8e9972bdb3b4d99a77a8c1fed528e21.json"}}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C", "orcid": "0000-0003-1279-1746", "researcher": {"href": "https://publications.scilifelab.se/researcher/e14e17d2cdb24a9f93991d83811c78b9.json"}}], "type": "journal article", "published": "2020-06-19", "journal": {"title": "Respir. Res.", "issn": "1465-993X", "volume": "21", "issue": "1", "pages": "155", "issn-l": "1465-9921"}, "abstract": "Asthma is a common and heterogeneous disease that includes subgroups characterized by type 2 (T2) or type 17 (T17) immune responses for which there is a need to identify the underlying mechanisms and biomarkers in order to develop specific therapies. These subgroups can be defined by airway epithelium gene signatures and the airway epithelium has also been implicated to play a significant role in asthma pathology. Extracellular vesicles (EVs) carry functional biomolecules and participate in cell-to-cell communication in both health and disease, properties that are likely to be involved in airway diseases such as asthma. The aim of this study was to identify stimulus-specific proteins and functionality of bronchial epithelium-derived EVs following stimulation with T2 or T17 cytokines.\n\nEVs from cytokine-stimulated (T2: IL-4 + IL-13 or T17: IL-17A + TNF\u03b1) human bronchial epithelial cells cultured at air-liquid interface (HBEC-ALI) were isolated by density cushion centrifugation and size exclusion chromatography and characterized with Western blotting and electron microscopy. Transcriptomic (cells) and proteomic (EVs) profiling was also performed.\n\nOur data shows that EVs are secreted and can be isolated from the apical side of HBEC-ALI and that cytokine stimulation increases EV release. Genes upregulated in cells stimulated with T2 or T17 cytokines were increased also on protein level in the EVs. Proteins found in T17-derived EVs were suggested to be involved in pathways related to neutrophil movement which was supported by assessing neutrophil chemotaxis ex vivo.\n\nTogether, the results suggest that epithelial EVs are involved in airway inflammation and that the EV proteome may be used for discovery of disease-specific mechanisms and signatures which may enable a precision medicine approach to the treatment of asthma.", "doi": "10.1186/s12931-020-01402-3", "pmid": "32560723", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7304225"}, {"db": "pii", "key": "10.1186/s12931-020-01402-3"}], "notes": [], "created": "2023-02-16T08:02:58.189Z", "modified": "2023-02-16T08:02:58.445Z"}, {"entity": "publication", "iuid": "e7a89f61f370498397e2d9bcb024aff8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e7a89f61f370498397e2d9bcb024aff8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e7a89f61f370498397e2d9bcb024aff8"}}, "title": "Ciliate mitoribosome illuminates evolutionary steps of mitochondrial translation.", "authors": [{"family": "Tobiasson", "given": "Victor", "initials": "V", "orcid": "0000-0001-8920-017X", "researcher": {"href": "https://publications.scilifelab.se/researcher/5208789057a94d0d9575476bf9c88d5a.json"}}, {"family": "Amunts", "given": "Alexey", "initials": "A", "orcid": "0000-0002-5302-1740", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7d0bf36ad1a47f5b5b88f78d1e15395.json"}}], "type": "journal article", "published": "2020-06-18", "journal": {"volume": "9", "issn": "2050-084X", "issue": null, "pages": "1-15", "title": "Elife", "issn-l": "2050-084X"}, "abstract": "To understand the steps involved in the evolution of translation, we used Tetrahymena thermophila, a ciliate with high coding capacity of the mitochondrial genome, as the model organism and characterized its mitochondrial ribosome (mitoribosome) using cryo-EM. The structure of the mitoribosome reveals an assembly of 94-ribosomal proteins and four-rRNAs with an additional protein mass of ~700 kDa on the small subunit, while the large subunit lacks 5S rRNA. The structure also shows that the small subunit head is constrained, tRNA binding sites are formed by mitochondria-specific protein elements, conserved protein bS1 is excluded, and bacterial RNA polymerase binding site is blocked. We provide evidence for anintrinsic protein targeting system through visualization of mitochondria-specific mL105 by the exit tunnel that would facilitate the recruitment of a nascent polypeptide. Functional protein uS3m is encoded by three complementary genes from the nucleus and mitochondrion, establishing a link between genetic drift and mitochondrial translation. Finally, we reannotated nine open reading frames in the mitochondrial genome that code for mitoribosomal proteins.", "doi": "10.7554/eLife.59264", "pmid": "32553108", "labels": {"Cryo-EM": "Service", "Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pii", "key": "59264"}, {"db": "pmc", "key": "PMC7326499"}], "notes": [], "created": "2020-06-20T05:52:44.314Z", "modified": "2021-11-10T12:50:13.521Z"}, {"entity": "publication", "iuid": "f5a7e37bfcd94531a0f810b49efccd16", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f5a7e37bfcd94531a0f810b49efccd16.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f5a7e37bfcd94531a0f810b49efccd16"}}, "title": "Removal of H2Aub1 by ubiquitin-specific proteases 12 and 13 is required for stable Polycomb-mediated gene repression in Arabidopsis.", "authors": [{"family": "Kralemann", "given": "Lejon E M", "initials": "LEM"}, {"family": "Liu", "given": "Shujing", "initials": "S"}, {"family": "Trejo-Arellano", "given": "Minerva S", "initials": "MS"}, {"family": "Mu\u00f1oz-Viana", "given": "Rafael", "initials": "R"}, {"family": "K\u00f6hler", "given": "Claudia", "initials": "C", "orcid": "0000-0002-2619-4857", "researcher": {"href": "https://publications.scilifelab.se/researcher/accd3f9307614c8ab67154dd5e50cdac.json"}}, {"family": "Hennig", "given": "Lars", "initials": "L"}], "type": "journal article", "published": "2020-06-16", "journal": {"title": "Genome Biol.", "issn": "1474-760X", "volume": "21", "issue": "1", "pages": "144", "issn-l": "1474-7596"}, "abstract": "Stable gene repression is essential for normal growth and development. Polycomb repressive complexes 1 and 2 (PRC1&2) are involved in this process by establishing monoubiquitination of histone 2A (H2Aub1) and subsequent trimethylation of lysine 27 of histone 3 (H3K27me3). Previous work proposed that H2Aub1 removal by the ubiquitin-specific proteases 12 and 13 (UBP12 and UBP13) is part of the repressive PRC1&2 system, but its functional role remains elusive.\n\nWe show that UBP12 and UBP13 work together with PRC1, PRC2, and EMF1 to repress genes involved in stimulus response. We find that PRC1-mediated H2Aub1 is associated with gene responsiveness, and its repressive function requires PRC2 recruitment. We further show that the requirement of PRC1 for PRC2 recruitment depends on the initial expression status of genes. Lastly, we demonstrate that removal of H2Aub1 by UBP12/13 prevents loss of H3K27me3, consistent with our finding that the H3K27me3 demethylase REF6 is positively associated with H2Aub1.\n\nOur data allow us to propose a model in which deposition of H2Aub1 permits genes to switch between repression and activation by H3K27me3 deposition and removal. Removal of H2Aub1 by UBP12/13 is required to achieve stable PRC2-mediated repression.", "doi": "10.1186/s13059-020-02062-8", "pmid": "32546254", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s13059-020-02062-8"}, {"db": "pmc", "key": "PMC7296913"}], "notes": [], "created": "2020-11-16T09:39:43.051Z", "modified": "2021-11-10T12:50:14.951Z"}, {"entity": "publication", "iuid": "2c7a1f9990c442bd9f733bc52293c119", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2c7a1f9990c442bd9f733bc52293c119.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2c7a1f9990c442bd9f733bc52293c119"}}, "title": "Chanjo: Clincal grade sequence coverage analysis", "authors": [{"family": "Andeer", "given": "Robin", "initials": "R"}, {"family": "Magnusson", "given": "M\u00e5ns", "initials": "M", "orcid": "0000-0002-0001-1047", "researcher": {"href": "https://publications.scilifelab.se/researcher/8e75a676a1bf4bfb80cf5ea579b44df0.json"}}, {"family": "Wedell", "given": "Anna", "initials": "A"}, {"family": "Stranneheim", "given": "Henrik", "initials": "H"}], "type": "journal-article", "published": "2020-06-16", "journal": {"title": "F1000Res", "issn": "2046-1402", "volume": "9", "issue": null, "pages": "615", "issn-l": "2046-1402"}, "abstract": null, "doi": "10.12688/f1000research.23605.1", "pmid": null, "labels": {"Clinical Genomics Stockholm": "Technology development", "Clinical Genomics": "Technology development"}, "xrefs": [], "notes": [], "created": "2020-11-22T16:12:00.707Z", "modified": "2021-11-10T12:38:31.323Z"}, {"entity": "publication", "iuid": "bc5dea45b8d148c38c3f0096804469f7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bc5dea45b8d148c38c3f0096804469f7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bc5dea45b8d148c38c3f0096804469f7"}}, "title": "A\u03b2(1-42) tetramer and octamer structures reveal edge conductivity pores as a mechanism for membrane damage.", "authors": [{"family": "Ciudad", "given": "Sonia", "initials": "S", "orcid": "0000-0002-9030-175X", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a5cf9b106604a72a8f873df97dab76e.json"}}, {"family": "Puig", "given": "Eduard", "initials": "E"}, {"family": "Botzanowski", "given": "Thomas", "initials": "T"}, {"family": "Meigooni", "given": "Moeen", "initials": "M"}, {"family": "Arango", "given": "Andres S", "initials": "AS"}, {"family": "Do", "given": "Jimmy", "initials": "J"}, {"family": "Mayzel", "given": "Maxim", "initials": "M", "orcid": "0000-0002-7413-0444", "researcher": {"href": "https://publications.scilifelab.se/researcher/467c29017024478692460a363ed9a945.json"}}, {"family": "Bayoumi", "given": "Mariam", "initials": "M"}, {"family": "Chaignepain", "given": "St\u00e9phane", "initials": "S"}, {"family": "Maglia", "given": "Giovanni", "initials": "G", "orcid": "0000-0003-2784-0811", "researcher": {"href": "https://publications.scilifelab.se/researcher/98d18f36cb0644029036fde5c55dff28.json"}}, {"family": "Cianferani", "given": "Sarah", "initials": "S"}, {"family": "Orekhov", "given": "Vladislav", "initials": "V"}, {"family": "Tajkhorshid", "given": "Emad", "initials": "E", "orcid": "0000-0001-8434-1010", "researcher": {"href": "https://publications.scilifelab.se/researcher/8ca6a74c70b14ccbaaa39b96415114b5.json"}}, {"family": "Bardiaux", "given": "Benjamin", "initials": "B", "orcid": "0000-0003-4014-9195", "researcher": {"href": "https://publications.scilifelab.se/researcher/f23e6431b8254c01bddb4279617d78f3.json"}}, {"family": "Carulla", "given": "Nat\u00e0lia", "initials": "N", "orcid": "0000-0002-3787-978X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a8e44e07561344299d0d29b03011a2ef.json"}}], "type": "journal article", "published": "2020-06-15", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "11", "issue": "1", "pages": "3014", "issn-l": "2041-1723"}, "abstract": "Formation of amyloid-beta (A\u03b2) oligomer pores in the membrane of neurons has been proposed to explain neurotoxicity in Alzheimer's disease (AD). Here, we present the three-dimensional structure of an A\u03b2 oligomer formed in a membrane mimicking environment, namely an A\u03b2(1-42) tetramer, which comprises a six stranded \u03b2-sheet core. The two faces of the \u03b2-sheet core are hydrophobic and surrounded by the membrane-mimicking environment while the edges are hydrophilic and solvent-exposed. By increasing the concentration of A\u03b2(1-42) in the sample, A\u03b2(1-42) octamers are also formed, made by two A\u03b2(1-42) tetramers facing each other forming a \u03b2-sandwich structure. Notably, A\u03b2(1-42) tetramers and octamers inserted into lipid bilayers as well-defined pores. To establish oligomer structure-membrane activity relationships, molecular dynamics simulations were carried out. These studies revealed a mechanism of membrane disruption in which water permeation occurred through lipid-stabilized pores mediated by the hydrophilic residues located on the core \u03b2-sheets edges of the oligomers.", "doi": "10.1038/s41467-020-16566-1", "pmid": "32541820", "labels": {"Swedish NMR Centre": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-16566-1"}, {"db": "pmc", "key": "PMC7296003"}], "notes": [], "created": "2020-12-11T09:17:34.243Z", "modified": "2025-10-17T13:03:56.893Z"}, {"entity": "publication", "iuid": "018fdd6411f84bdd84b41881ac4dfee7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/018fdd6411f84bdd84b41881ac4dfee7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/018fdd6411f84bdd84b41881ac4dfee7"}}, "title": "Integrated transcriptomic and genomic analysis improves prediction of complete remission and survival in elderly patients with acute myeloid leukemia.", "authors": [{"family": "\u00d6sterroos", "given": "Albin", "initials": "A", "orcid": "0000-0001-8749-7299", "researcher": {"href": "https://publications.scilifelab.se/researcher/47a3ea9e722b4c72a7f00a61b5c9fe0a.json"}}, {"family": "Bj\u00f6rklund", "given": "My", "initials": "M", "orcid": "0000-0002-2325-6012", "researcher": {"href": "https://publications.scilifelab.se/researcher/3cc743cdb2604ffdbc78303d70985c48.json"}}, {"family": "Eriksson", "given": "Anna", "initials": "A"}, {"family": "Lindberg", "given": "Johan", "initials": "J"}, {"family": "Nilsson", "given": "Christer", "initials": "C", "orcid": "0000-0003-0695-0050", "researcher": {"href": "https://publications.scilifelab.se/researcher/7f78180b33fa48cd86474d5c3cdaa852.json"}}, {"family": "Mareschal", "given": "Sylvain", "initials": "S"}, {"family": "Rantalainen", "given": "Mattias", "initials": "M"}, {"family": "Gr\u00f6nberg", "given": "Henrik", "initials": "H"}, {"family": "Lehmann", "given": "S\u00f6ren", "initials": "S"}], "type": "journal article", "published": "2020-06-11", "journal": {"title": "Blood Cancer J", "issn": "2044-5385", "volume": "10", "issue": "6", "pages": "67", "issn-l": "2044-5385"}, "abstract": "Relevant molecular tools for treatment stratification of patients \u226565 years with acute myeloid leukemia (AML) are lacking. We combined clinical data with targeted DNA- and full RNA-sequencing of 182 intensively and palliatively treated patients to predict complete remission (CR) and survival in AML patients \u226565 years. Intensively treated patients with NPM1 and IDH2R172 mutations had longer overall survival (OS), whereas mutated TP53 conferred lower CR rates and shorter OS. FLT3-ITD and TP53 mutations predicted worse OS in palliatively treated patients. Gene expression levels most predictive of CR were combined with somatic mutations for an integrated risk stratification that we externally validated using the beatAML cohort. We defined a high-risk group with a CR rate of 20% in patients with mutated TP53, compared to 97% CR in low-risk patients defined by high expression of ZBTB7A and EEPD1 without TP53 mutations. Patients without these criteria had a CR rate of 54% (intermediate risk). The difference in CR rates translated into significant OS differences that outperformed ELN stratification for OS prediction. The results suggest that an integrated molecular risk stratification can improve prediction of CR and OS and could be used to guide treatment in elderly AML patients.", "doi": "10.1038/s41408-020-0332-3", "pmid": "32527994", "labels": {"Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7289793"}, {"db": "pii", "key": "10.1038/s41408-020-0332-3"}], "notes": [], "created": "2023-11-27T21:46:41.988Z", "modified": "2024-01-16T13:48:42.374Z"}, {"entity": "publication", "iuid": "8d78208f9c61424e8b5e04dceec58d6b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8d78208f9c61424e8b5e04dceec58d6b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8d78208f9c61424e8b5e04dceec58d6b"}}, "title": "Illuminating Genetic Mysteries of the Dead Sea Scrolls.", "authors": [{"family": "Anava", "given": "Sarit", "initials": "S"}, {"family": "Neuhof", "given": "Moran", "initials": "M"}, {"family": "Gingold", "given": "Hila", "initials": "H"}, {"family": "Sagy", "given": "Or", "initials": "O"}, {"family": "Munters", "given": "Arielle", "initials": "A"}, {"family": "Svensson", "given": "Emma M", "initials": "EM"}, {"family": "Afshinnekoo", "given": "Ebrahim", "initials": "E"}, {"family": "Danko", "given": "David", "initials": "D"}, {"family": "Foox", "given": "Jonathan", "initials": "J"}, {"family": "Shor", "given": "Pnina", "initials": "P"}, {"family": "Riestra", "given": "Beatriz", "initials": "B"}, {"family": "Huchon", "given": "Doroth\u00e9e", "initials": "D"}, {"family": "Mason", "given": "Christopher E", "initials": "CE"}, {"family": "Mizrahi", "given": "Noam", "initials": "N"}, {"family": "Jakobsson", "given": "Mattias", "initials": "M"}, {"family": "Rechavi", "given": "Oded", "initials": "O"}], "type": "historical article", "published": "2020-06-11", "journal": {"title": "Cell", "issn": "1097-4172", "volume": "181", "issue": "6", "pages": "1218-1231.e27", "issn-l": "0092-8674"}, "abstract": "The discovery of the 2,000-year-old Dead Sea Scrolls had an incomparable impact on the historical understanding of Judaism and Christianity. \"Piecing together\" scroll fragments is like solving jigsaw puzzles with an unknown number of missing parts. We used the fact that most scrolls are made from animal skins to \"fingerprint\" pieces based on DNA sequences. Genetic sorting of the scrolls illuminates their textual relationship and historical significance. Disambiguating the contested relationship between Jeremiah fragments supplies evidence that some scrolls were brought to the Qumran caves from elsewhere; significantly, they demonstrate that divergent versions of Jeremiah circulated in parallel throughout Israel (ancient Judea). Similarly, patterns discovered in non-biblical scrolls, particularly the Songs of the Sabbath Sacrifice, suggest that the Qumran scrolls represent the broader cultural milieu of the period. Finally, genetic analysis divorces debated fragments from the Qumran scrolls. Our study demonstrates that interdisciplinary approaches enrich the scholar's toolkit.", "doi": "10.1016/j.cell.2020.04.046", "pmid": "32492404", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S0092-8674(20)30552-3"}], "notes": [], "created": "2020-06-03T09:42:05.526Z", "modified": "2024-01-16T13:48:42.381Z"}, {"entity": "publication", "iuid": "8e84f5a3ca5548628b22e3d122c5eed6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8e84f5a3ca5548628b22e3d122c5eed6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8e84f5a3ca5548628b22e3d122c5eed6"}}, "title": "Distinct pre-initiation steps in human mitochondrial translation.", "authors": [{"family": "Khawaja", "given": "Anas", "initials": "A"}, {"family": "Itoh", "given": "Yuzuru", "initials": "Y", "orcid": "0000-0001-7802-5572", "researcher": {"href": "https://publications.scilifelab.se/researcher/12516bf2aeb44f9ba7e380b7be1bf582.json"}}, {"family": "Remes", "given": "Cristina", "initials": "C"}, {"family": "Sp\u00e5hr", "given": "Henrik", "initials": "H"}, {"family": "Yukhnovets", "given": "Olessya", "initials": "O"}, {"family": "H\u00f6fig", "given": "Henning", "initials": "H", "orcid": "0000-0003-0506-783X", "researcher": {"href": "https://publications.scilifelab.se/researcher/b5d914f8854e4010949124154dfa1539.json"}}, {"family": "Amunts", "given": "Alexey", "initials": "A", "orcid": "0000-0002-5302-1740", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7d0bf36ad1a47f5b5b88f78d1e15395.json"}}, {"family": "Rorbach", "given": "Joanna", "initials": "J", "orcid": "0000-0002-2891-2840", "researcher": {"href": "https://publications.scilifelab.se/researcher/a069374613a7403b818ce7ca400f3627.json"}}], "type": "journal article", "published": "2020-06-10", "journal": {"volume": "11", "issn": "2041-1723", "issue": "1", "pages": "2932", "title": "Nat Commun", "issn-l": "2041-1723"}, "abstract": "Translation initiation in human mitochondria relies upon specialized mitoribosomes and initiation factors, mtIF2 and mtIF3, which have diverged from their bacterial counterparts. Here we report two distinct mitochondrial pre-initiation assembly steps involving those factors. Single-particle cryo-EM revealed that in the first step, interactions between mitochondria-specific protein mS37 and mtIF3 keep the small mitoribosomal subunit in a conformation favorable for a subsequent accommodation of mtIF2 in the second step. Combination with fluorescence cross-correlation spectroscopy analyses suggests that mtIF3 promotes complex assembly without mRNA or initiator tRNA binding, where exclusion is achieved by the N-terminal and C-terminal domains of mtIF3. Finally, the association of large mitoribosomal subunit is required for initiator tRNA and leaderless mRNA recruitment to form a stable initiation complex. These data reveal fundamental aspects of mammalian protein synthesis that are specific to mitochondria.", "doi": "10.1038/s41467-020-16503-2", "pmid": "32522994", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-16503-2"}, {"db": "pmc", "key": "PMC7287080"}], "notes": [], "created": "2020-06-20T05:51:40.998Z", "modified": "2021-11-10T12:50:19.697Z"}, {"entity": "publication", "iuid": "e913056a4e7f4aad822efbc06d4f28d5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e913056a4e7f4aad822efbc06d4f28d5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e913056a4e7f4aad822efbc06d4f28d5"}}, "title": "Whole-genome sequencing of glioblastoma reveals enrichment of non-coding constraint mutations in known and novel genes.", "authors": [{"family": "Sakthikumar", "given": "Sharadha", "initials": "S"}, {"family": "Roy", "given": "Ananya", "initials": "A"}, {"family": "Haseeb", "given": "Lulu", "initials": "L"}, {"family": "Pettersson", "given": "Mats E", "initials": "ME"}, {"family": "Sundstr\u00f6m", "given": "Elisabeth", "initials": "E"}, {"family": "Marinescu", "given": "Voichita D", "initials": "VD"}, {"family": "Lindblad-Toh", "given": "Kerstin", "initials": "K", "orcid": "0000-0001-8338-0253", "researcher": {"href": "https://publications.scilifelab.se/researcher/e0063145f7d6476f80ab42f94833f4cf.json"}}, {"family": "Forsberg-Nilsson", "given": "Karin", "initials": "K", "orcid": "0000-0003-0692-6245", "researcher": {"href": "https://publications.scilifelab.se/researcher/5da04859250141a0a7271a69c7da9176.json"}}], "type": "journal article", "published": "2020-06-09", "journal": {"title": "Genome Biol.", "issn": "1474-760X", "volume": "21", "issue": "1", "pages": "127", "issn-l": "1474-7596"}, "abstract": "Glioblastoma (GBM) has one of the worst 5-year survival rates of all cancers. While genomic studies of the disease have been performed, alterations in the non-coding regulatory regions of GBM have largely remained unexplored. We apply whole-genome sequencing (WGS) to identify non-coding mutations, with regulatory potential in GBM, under the hypothesis that regions of evolutionary constraint are likely to be functional, and somatic mutations are likely more damaging than in unconstrained regions.\n\nWe validate our GBM cohort, finding similar copy number aberrations and mutated genes based on coding mutations as previous studies. Performing analysis on non-coding constraint mutations and their position relative to nearby genes, we find a significant enrichment of non-coding constraint mutations in the neighborhood of 78 genes that have previously been implicated in GBM. Among them, SEMA3C and DYNC1I1 show the highest frequencies of alterations, with multiple mutations overlapping transcription factor binding sites. We find that a non-coding constraint mutation in the SEMA3C promoter reduces the DNA binding capacity of the region. We also identify 1776 other genes enriched for non-coding constraint mutations with likely regulatory potential, providing additional candidate GBM genes. The mutations in the top four genes, DLX5, DLX6, FOXA1, and ISL1, are distributed over promoters, UTRs, and multiple transcription factor binding sites.\n\nThese results suggest that non-coding constraint mutations could play an essential role in GBM, underscoring the need to connect non-coding genomic variation to biological function and disease pathology.", "doi": "10.1186/s13059-020-02035-x", "pmid": "32513296", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support, Infrastructure and Training": "Service", "Bioinformatics Long-term Support WABI": "Service", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s13059-020-02035-x"}, {"db": "pmc", "key": "PMC7281935"}], "notes": [], "created": "2020-06-10T22:06:24.696Z", "modified": "2024-01-16T13:48:42.389Z"}, {"entity": "publication", "iuid": "904c71ceedcb4cc6b762f9aaab8e6888", "links": {"self": {"href": "https://publications.scilifelab.se/publication/904c71ceedcb4cc6b762f9aaab8e6888.json"}, "display": {"href": "https://publications.scilifelab.se/publication/904c71ceedcb4cc6b762f9aaab8e6888"}}, "title": "Sales of antibiotics and occurrence of resistance in Sweden", "authors": [], "type": null, "published": "2020-06-09", "journal": {"title": "Swedres-Svarm", "issn": "1650-6332", "volume": "19088", "issue": null, "pages": "1-128", "issn-l": null}, "abstract": "Swedres-Svarm 2019 shows statistics on antibiotic sales and antibiotic resistance in bacteria from both humans and animals. The report is a co-production between the Public Health Agency of Sweden the National Veterinary Institute (SVA).\r\n\r\nThis report is mainly aimed at professionals within:\r\n\r\nSTRAMA\r\nClinical microbiological laboratories\r\nAntimicrobial stewardship\r\nInfection prevention and control\r\nCommunicable disease control", "doi": null, "pmid": null, "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [], "notes": [], "created": "2020-11-22T14:25:40.247Z", "modified": "2020-11-22T14:25:40.248Z"}, {"entity": "publication", "iuid": "9818497461264e91949fb2485a056d4b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9818497461264e91949fb2485a056d4b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9818497461264e91949fb2485a056d4b"}}, "title": "High genomic-based predicted strain coverage among invasive meningococcal isolates when combining Bexsero and Trumenba vaccines.", "authors": [{"family": "S\u00e4ll", "given": "Olof", "initials": "O"}, {"family": "Olofsson", "given": "Emma", "initials": "E"}, {"family": "Jacobsson", "given": "Susanne", "initials": "S"}], "type": "journal article", "published": "2020-06-09", "journal": {"title": "Vaccine", "issn": "1873-2518", "volume": "38", "issue": "28", "pages": "4374-4378", "issn-l": null}, "abstract": "Two protein-based vaccines (Bexsero\u00ae and Trumenba\u00ae) are licensed for invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup B (MenB). The aim of this study was to evaluate the possible protection of these vaccines, based on the genomic profiles of IMD isolates. All invasive meningococcal isolates in Sweden during 2014-2018 (n = 242) were analyzed with the vaccine coverage scheme available at the PubMLST database. The overall estimated genomic strain coverage among the Swedish invasive meningococcal isolates was 55% for Bexsero and 57% for Trumenba (p = 0.714). The estimated serogroup-specific coverage for Bexsero respectively Trumenba was: MenB; 67% and 90% (p < 0.05), MenW; 93% and 4% (p < 0.05), MenC; 87% and 30% (p < 0.05) and MenY; 1% and 96% (p < 0.05). With the combination of the two vaccines, the potential genomic-based strain coverage was 95%, indicating a possible additive effect of combining Bexsero and Trumenba, which, however, needs to be confirmed by analysis of phenotypic antigen expression.", "doi": "10.1016/j.vaccine.2020.04.074", "pmid": "32414653", "labels": {"Clinical Genomics \u00d6rebro": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0264-410X(20)30591-0"}], "notes": [], "created": "2020-11-27T14:08:27.564Z", "modified": "2021-12-08T12:30:48.656Z"}, {"entity": "publication", "iuid": "2b160d0829af493f9894f3148bb0ad8f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2b160d0829af493f9894f3148bb0ad8f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2b160d0829af493f9894f3148bb0ad8f"}}, "title": "CYCLIN-B1/2 and -D1 act in opposition to coordinate cortical progenitor self-renewal and lineage commitment.", "authors": [{"family": "Hagey", "given": "Daniel W", "initials": "DW", "orcid": "0000-0001-9246-6235", "researcher": {"href": "https://publications.scilifelab.se/researcher/e9b5df8185a54da58f080ea7a7b956ef.json"}}, {"family": "Topcic", "given": "Danijal", "initials": "D"}, {"family": "Kee", "given": "Nigel", "initials": "N"}, {"family": "Reynaud", "given": "Florie", "initials": "F"}, {"family": "Bergsland", "given": "Maria", "initials": "M"}, {"family": "Perlmann", "given": "Thomas", "initials": "T"}, {"family": "Muhr", "given": "Jonas", "initials": "J", "orcid": "0000-0003-0704-0788", "researcher": {"href": "https://publications.scilifelab.se/researcher/b6a665f02acc432e9d80feb5c61f4572.json"}}], "type": "journal article", "published": "2020-06-09", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "11", "issue": "1", "pages": "2898", "issn-l": "2041-1723"}, "abstract": "The sequential generation of layer-specific cortical neurons requires radial glia cells (RGCs) to precisely balance self-renewal and lineage commitment. While specific cell-cycle phases have been associated with these decisions, the mechanisms linking the cell-cycle machinery to cell-fate commitment remain obscure. Using single-cell RNA-sequencing, we find that the strongest transcriptional signature defining multipotent RGCs is that of G2/M-phase, and particularly CYCLIN-B1/2, while lineage-committed progenitors are enriched in G1/S-phase genes, including CYCLIN-D1. These data also reveal cell-surface markers that allow us to isolate RGCs and lineage-committed progenitors, and functionally confirm the relationship between cell-cycle phase enrichment and cell fate competence. Finally, we use cortical electroporation to demonstrate that CYCLIN-B1/2 cooperate with CDK1 to maintain uncommitted RGCs by activating the NOTCH pathway, and that CYCLIN-D1 promotes differentiation. Thus, this work establishes that cell-cycle phase-specific regulators act in opposition to coordinate the self-renewal and lineage commitment of RGCs via core stem cell regulatory pathways.", "doi": "10.1038/s41467-020-16597-8", "pmid": "32518258", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-16597-8"}, {"db": "pmc", "key": "PMC7283355"}], "notes": [], "created": "2020-12-07T16:26:58.923Z", "modified": "2024-01-16T13:48:42.396Z"}, {"entity": "publication", "iuid": "2dadaa51e19d416ba463c2fc9ac561b3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2dadaa51e19d416ba463c2fc9ac561b3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2dadaa51e19d416ba463c2fc9ac561b3"}}, "title": "The regulation and pharmacological modulation of immune complex induced type III IFN production by plasmacytoid dendritic cells.", "authors": [{"family": "Hjorton", "given": "Karin", "initials": "K"}, {"family": "Hagberg", "given": "Niklas", "initials": "N"}, {"family": "Pucholt", "given": "Pascal", "initials": "P"}, {"family": "Eloranta", "given": "Maija-Leena", "initials": "ML"}, {"family": "R\u00f6nnblom", "given": "Lars", "initials": "L"}], "type": "journal article", "published": "2020-06-05", "journal": {"title": "Arthritis Res. Ther.", "issn": "1478-6362", "issn-l": "1478-6354", "volume": "22", "issue": "1", "pages": "130"}, "abstract": "Patients with systemic lupus erythematosus (SLE) have an ongoing interferon (IFN) production due to an activation of plasmacytoid dendritic cells (pDCs), which can be triggered to type I IFN synthesis by RNA containing immune complexes (RNA-IC). Considering emerging data suggesting a role of type III IFN in the SLE disease process, we asked if RNA-IC can induce type III IFN production in pDC and how this production can be regulated.\n\nPeripheral blood mononuclear cells (PBMCs) or immune cell subsets were isolated from healthy blood donors or SLE patients and stimulated with IC containing U1 snRNP and SLE-IgG (RNA-IC). Hydroxychloroquine (HCQ) and an interleukin receptor 1-associated kinase 4 inhibitor (IRAK4i) were added to cell cultures. Cytokine mRNA levels were determined with a microarray and protein levels with immunoassays. Single-cell RNA sequencing of pDCs using ddSEQ technology was performed.\n\nType III IFN mRNA and protein was induced in RNA-IC-stimulated pDC-NK and pDC-B cell co-cultures. A subset of activated pDCs (3%) expressed both type III and type I IFN mRNA. IFN-\u03bb2, IFN-\u03b12b, interleukin (IL)-3, IL-6, or granulocyte-macrophage colony-stimulating factor (GM-CSF) enhanced IFN-\u03bb1/3 production 2-5-fold. HCQ and an IRAK4i blocked the RNA-IC-triggered IFN-\u03bb1/3 production (p < 0.01). IFN-\u03b12b and GM-CSF increased the proportion of SLE patients producing IFN-\u03bb1/3 in response to RNA-IC from 11 to 33%.\n\nType III IFN production is triggered by RNA-IC in pDCs in a TLR-MyD88-dependent manner, enhanced by NK and B cells as well as several pro-inflammatory cytokines. These results support a contributing role for both type I and type III IFNs in SLE, which needs to be considered when targeting the IFN system in this disease.", "doi": "10.1186/s13075-020-02186-z", "pmid": "32503683", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s13075-020-02186-z"}, {"db": "pmc", "key": "PMC7275601"}], "notes": [], "created": "2020-06-08T05:31:54.214Z", "modified": "2024-01-16T13:48:42.402Z"}, {"entity": "publication", "iuid": "65338b6f4c55448b9e4454def5c0cc0d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/65338b6f4c55448b9e4454def5c0cc0d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/65338b6f4c55448b9e4454def5c0cc0d"}}, "title": "LPS-treatment of bovine endometrial epithelial cells causes differential DNA methylation of genes associated with inflammation and endometrial function.", "authors": [{"family": "Jhamat", "given": "Naveed", "initials": "N"}, {"family": "Niazi", "given": "Adnan", "initials": "A", "orcid": "0000-0003-0311-5279", "researcher": {"href": "https://publications.scilifelab.se/researcher/c9e07c9891804a60980eb07956a7cd0d.json"}}, {"family": "Guo", "given": "Yongzhi", "initials": "Y"}, {"family": "Chanrot", "given": "Metasu", "initials": "M"}, {"family": "Ivanova", "given": "Elena", "initials": "E"}, {"family": "Kelsey", "given": "Gavin", "initials": "G"}, {"family": "Bongcam-Rudloff", "given": "Erik", "initials": "E"}, {"family": "Andersson", "given": "G\u00f6ran", "initials": "G"}, {"family": "Humblot", "given": "Patrice", "initials": "P"}], "type": "journal article", "published": "2020-06-03", "journal": {"title": "BMC Genomics", "issn": "1471-2164", "volume": "21", "issue": "1", "pages": "385", "issn-l": "1471-2164"}, "abstract": "Lipopolysaccharide (LPS) endotoxin stimulates pro-inflammatory pathways and is a key player in the pathological mechanisms involved in the development of endometritis. This study aimed to investigate LPS-induced DNA methylation changes in bovine endometrial epithelial cells (bEECs), which may affect endometrial function. Following in vitro culture, bEECs from three cows were either untreated (0) or exposed to 2 and 8 \u03bcg/mL LPS for 24 h.\n\nDNA samples extracted at 0 h and 24 h were sequenced using reduced representation bisulfite sequencing (RRBS). When comparing DNA methylation results at 24 h to time 0 h, a larger proportion of hypomethylated regions were identified in the LPS-treated groups, whereas the trend was opposite in controls. When comparing LPS groups to controls at 24 h, a total of 1291 differentially methylated regions (DMRs) were identified (55% hypomethylated and 45% hypermethylated). Integration of DNA methylation data obtained here with our previously published gene expression data obtained from the same samples showed a negative correlation (r = - 0.41 for gene promoter, r = - 0.22 for gene body regions, p < 0.05). Differential methylation analysis revealed that effects of LPS treatment were associated with methylation changes for genes involved in regulation of immune and inflammatory responses, cell adhesion, and external stimuli. Gene ontology and pathway analyses showed that most of the differentially methylated genes (DMGs) were associated with cell proliferation and apoptotic processes; and pathways such as calcium-, oxytocin- and MAPK-signaling pathways with recognized roles in innate immunity. Several DMGs were related to systemic inflammation and tissue re-modelling including HDAC4, IRAK1, AKT1, MAP3K6, Wnt7A and ADAMTS17.\n\nThe present results show that LPS altered the DNA methylation patterns of bovine endometrial epithelial cells. This information, combined with our previously reported changes in gene expression related to endometrial function, confirm that LPS activates pro-inflammatory mechanisms leading to perturbed immune balance and cell adhesion processes in the endometrium.", "doi": "10.1186/s12864-020-06777-7", "pmid": "32493210", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12864-020-06777-7"}, {"db": "pmc", "key": "PMC7268755"}], "notes": [], "created": "2020-06-09T14:54:11.383Z", "modified": "2024-01-16T13:48:42.410Z"}, {"entity": "publication", "iuid": "44020fff10634a05bc74ad21850e4a0a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/44020fff10634a05bc74ad21850e4a0a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/44020fff10634a05bc74ad21850e4a0a"}}, "title": "Radiation Triggers a Dynamic Sequence of Transient Microglial Alterations in Juvenile Brain.", "authors": [{"family": "Osman", "given": "Ahmed M", "initials": "AM"}, {"family": "Sun", "given": "Ying", "initials": "Y"}, {"family": "Burns", "given": "Terry C", "initials": "TC"}, {"family": "He", "given": "Liqun", "initials": "L"}, {"family": "Kee", "given": "Nigel", "initials": "N"}, {"family": "Oliva-Vilarnau", "given": "Nuria", "initials": "N"}, {"family": "Alevyzaki", "given": "Androniki", "initials": "A"}, {"family": "Zhou", "given": "Kai", "initials": "K"}, {"family": "Louhivuori", "given": "Lauri", "initials": "L"}, {"family": "Uhl\u00e9n", "given": "Per", "initials": "P"}, {"family": "Hedlund", "given": "Eva", "initials": "E"}, {"family": "Betsholtz", "given": "Christer", "initials": "C"}, {"family": "Lauschke", "given": "Volker M", "initials": "VM"}, {"family": "Kele", "given": "Julianna", "initials": "J"}, {"family": "Blomgren", "given": "Klas", "initials": "K"}], "type": "journal article", "published": "2020-06-02", "journal": {"title": "Cell Rep", "issn": "2211-1247", "volume": "31", "issue": "9", "pages": "107699", "issn-l": null}, "abstract": "Cranial irradiation (IR), an effective tool to treat malignant brain tumors, triggers a chronic pro-inflammatory microglial response, at least in the adult brain. Using single-cell and bulk RNA sequencing, combined with histology, we show that the microglial response in the juvenile mouse hippocampus is rapid but returns toward normal within 1 week. The response is characterized by a series of temporally distinct homeostasis-, sensome-, and inflammation-related molecular signatures. We find that a single microglial cell simultaneously upregulates transcripts associated with pro- and anti-inflammatory microglial phenotypes. Finally, we show that juvenile and adult irradiated microglia are already transcriptionally distinct in the early phase after IR. Our results indicate that microglia are involved in the initial stages but may not be responsible for driving long-term inflammation in the juvenile brain.", "doi": "10.1016/j.celrep.2020.107699", "pmid": "32492415", "labels": {"Eukaryotic Single Cell Genomics (ESCG)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S2211-1247(20)30669-0"}], "notes": [], "created": "2020-10-06T11:04:52.403Z", "modified": "2024-01-16T13:48:42.418Z"}, {"entity": "publication", "iuid": "b069a230bccd448eb4a10bd0165f8c5d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b069a230bccd448eb4a10bd0165f8c5d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b069a230bccd448eb4a10bd0165f8c5d"}}, "title": "Vegetation type determines spore deposition within a forest-agricultural mosaic landscape.", "authors": [{"family": "Redondo", "given": "Miguel A", "initials": "MA", "orcid": "0000-0002-6383-5457", "researcher": {"href": "https://publications.scilifelab.se/researcher/24e77c460a3e4bc18efed51d74c53742.json"}}, {"family": "Berlin", "given": "Anna", "initials": "A", "orcid": "0000-0002-9518-5719", "researcher": {"href": "https://publications.scilifelab.se/researcher/023743c670cc408bb4ed767cb8ee558a.json"}}, {"family": "Boberg", "given": "Johanna", "initials": "J", "orcid": "0000-0002-1300-8883", "researcher": {"href": "https://publications.scilifelab.se/researcher/e913853413c740d88f6d1b3b630dfccd.json"}}, {"family": "Oliva", "given": "Jon\u00e0s", "initials": "J", "orcid": "0000-0003-2418-2542", "researcher": {"href": "https://publications.scilifelab.se/researcher/ea605d40772449298a04cbf0b4b01de5.json"}}], "type": "journal article", "published": "2020-06-01", "journal": {"title": "FEMS Microbiol. Ecol.", "issn": "1574-6941", "volume": "96", "issue": "6", "pages": null, "issn-l": "0168-6496"}, "abstract": "Predicting fungal community assembly is partly limited by our understanding of the factors driving the composition of deposited spores. We studied the relative contribution of vegetation, geographical distance, seasonality and weather to fungal spore deposition across three vegetation types. Active and passive spore traps were established in agricultural fields, deciduous forests and coniferous forests across a geographic gradient of \u223c600 km. Active traps captured the spore community suspended in air, reflecting the potential deposition, whereas passive traps reflected realized deposition. Fungal species were identified by metabarcoding of the ITS2 region. The composition of spore communities captured by passive traps differed more between vegetation types than across regions separated by >100 km, indicating that vegetation type was the strongest driver of composition of deposited spores. By contrast, vegetation contributed less to potential deposition, which followed a seasonal pattern. Within the same site, the spore communities captured by active traps differed from those captured by passive traps. Realized deposition tended to be dominated by spores of species related to vegetation. Temperature was negatively correlated with the fungal species richness of both potential and realized deposition. Our results indicate that vegetation may be able to maintain similar fungal communities across distances, and likely be the driving factor of fungal spore deposition at landscape level.", "doi": "10.1093/femsec/fiaa082", "pmid": "32356889", "labels": {"NGI Uppsala (Uppsala Genome Center)": null, "National Genomics Infrastructure": null}, "xrefs": [{"db": "pii", "key": "5827636"}, {"db": "pmc", "key": "PMC7239601"}, {"db": "figshare", "key": "10.6084/m9.figshare.10012058.v5"}], "notes": [], "created": "2020-09-15T06:20:53.690Z", "modified": "2021-11-10T12:50:28.016Z"}, {"entity": "publication", "iuid": "60cb5c21673847068a71fc34addf5983", "links": {"self": {"href": "https://publications.scilifelab.se/publication/60cb5c21673847068a71fc34addf5983.json"}, "display": {"href": "https://publications.scilifelab.se/publication/60cb5c21673847068a71fc34addf5983"}}, "title": "Normal murine respiratory tract has its mucus concentrated in clouds based on the Muc5b mucin.", "authors": [{"family": "Fakih", "given": "Dalia", "initials": "D"}, {"family": "Rodriguez-Pi\u00f1eiro", "given": "Ana M", "initials": "AM"}, {"family": "Trillo-Muyo", "given": "Sergio", "initials": "S"}, {"family": "Evans", "given": "Christopher M", "initials": "CM"}, {"family": "Ermund", "given": "Anna", "initials": "A"}, {"family": "Hansson", "given": "Gunnar C", "initials": "GC"}], "type": "journal article", "published": "2020-06-01", "journal": {"title": "Am J Physiol Lung Cell Mol Physiol", "issn": "1522-1504", "volume": "318", "issue": "6", "pages": "L1270-L1279", "issn-l": null}, "abstract": "The organization of the normal airway mucus system differs in small experimental animals from that in humans and large mammals. To address normal murine airway mucociliary clearance, Alcian blue-stained mucus transport was measured ex vivo on tracheal tissues of na\u00efve C57BL/6, Muc5b-/-, Muc5ac-/-, and EGFP-tagged Muc5b reporter mice. Close to the larynx with a few submucosal glands, the mucus appeared as thick bundles. More distally in the trachea and in large bronchi, Alcian blue-stained mucus was organized in cloud-like formations based on the Muc5b mucin. On tilted tissue, the mucus clouds moved upward toward the larynx with an average velocity of 12 \u00b5m/s compared with 20 \u00b5m/s for beads not associated with clouds. In Muc5ac-/- mice, Muc5b formed mucus strands attached to the tissue surface, while in Muc5b-/- mice, Muc5ac had a more variable appearance. The normal mouse lung mucus thus appears as discontinuous clouds, clearly different from the stagnant mucus layer in diseased lungs.", "doi": "10.1152/ajplung.00485.2019", "pmid": "32348677", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7347266"}], "notes": [], "created": "2023-02-16T08:06:59.330Z", "modified": "2023-02-16T08:06:59.332Z"}, {"entity": "publication", "iuid": "431359fd167a4268bb3b12e8f46948c2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/431359fd167a4268bb3b12e8f46948c2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/431359fd167a4268bb3b12e8f46948c2"}}, "title": "In-plate toxicometabolomics of single zebrafish embryos.", "authors": [{"family": "Ribbenstedt", "given": "Anton", "initials": "A", "orcid": "0000-0002-9985-5644", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a407ce29c19408cb4d2bd281e299154.json"}}, {"family": "Posselt", "given": "Malte", "initials": "M", "orcid": "0000-0001-8979-8044", "researcher": {"href": "https://publications.scilifelab.se/researcher/e1b4854ced5246e8a3b79d6ab03cdde1.json"}}, {"family": "Brunius", "given": "Carl", "initials": "C", "orcid": "0000-0003-3957-870X", "researcher": {"href": "https://publications.scilifelab.se/researcher/560a5d14ee83421680058b00df2ac9e2.json"}}, {"family": "Benskin", "given": "Jonathan P", "initials": "JP", "orcid": "0000-0001-5940-637X", "researcher": {"href": "https://publications.scilifelab.se/researcher/c1403a2509a34819adf12e71b8e53982.json"}}], "type": "journal article", "published": "2020-06-01", "journal": {"title": "Mol Omics", "issn": "2515-4184", "volume": "16", "issue": "3", "pages": "185-194", "issn-l": "2515-4184"}, "abstract": "Toxicometabolomic studies involving zebrafish embryos have become increasingly popular for linking apical endpoints to biochemical perturbations as part of adverse outcome pathway determination. These experiments involve pooling embryos to generate sufficient biomass for metabolomic measurement, which adds both time and cost. To address this limitation, we developed a high-throughput toxicometabolomic assay involving single zebrafish embryos. Incubation, microscopy, embryo extraction, and instrumental metabolomic analysis were all performed in the same 96-well plate, following acquisition of conventional toxicological endpoints. The total time for the assay (including testing of 6 doses/n = 12 embryos per dose plus positive and negative controls, assessing conventional endpoints, instrumental analysis, data processing and multivariate statistics) is <14 days. Metabolomic perturbations at low dose were linked statistically to those observed at high dose and in the presence of an adverse effect, thereby contextualizing omic data amongst apical endpoints. Overall, this assay enables collection of high resolution metabolomic data in a high throughput manner, suitable for mode of action hypothesis generation in the context of pharmaceutical or toxicological screening.", "doi": "10.1039/d0mo00007h", "pmid": "32191256", "labels": {"Genome Engineering Zebrafish": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "Dryad", "key": "10.5061/dryad.7m0cfxppz"}], "notes": [], "created": "2020-03-17T08:24:22.807Z", "modified": "2024-01-16T13:48:42.430Z"}, {"entity": "publication", "iuid": "d5a875da3329432092ef2545fdf51dfd", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d5a875da3329432092ef2545fdf51dfd.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d5a875da3329432092ef2545fdf51dfd"}}, "title": "Genomic analysis and antimicrobial resistance of Neisseria gonorrhoeae isolates from Vietnam in 2011 and 2015-16.", "authors": [{"family": "Lan", "given": "Pham Thi", "initials": "PT"}, {"family": "Golparian", "given": "Daniel", "initials": "D"}, {"family": "Ringlander", "given": "Johan", "initials": "J"}, {"family": "Van Hung", "given": "Le", "initials": "L"}, {"family": "Van Thuong", "given": "Nguyen", "initials": "N"}, {"family": "Unemo", "given": "Magnus", "initials": "M", "orcid": "0000-0003-1710-2081", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f1494bae3b140a3a8761092e420a5de.json"}}], "type": "journal article", "published": "2020-06-01", "journal": {"title": "J. Antimicrob. Chemother.", "issn": "1460-2091", "issn-l": "0305-7453", "volume": "75", "issue": "6", "pages": "1432-1438"}, "abstract": "Antimicrobial resistance (AMR) in Neisseria gonorrhoeae, compromising gonorrhoea treatment, is a threat to reproductive health globally. South-East and East Asia have been major sources of emergence and subsequent international spread of AMR gonococcal strains during recent decades. We investigated gonococcal isolates from 2011 and 2015-16 in Vietnam using AMR testing, WGS and detection of AMR determinants.\r\n\r\nTwo hundred and twenty-nine gonococcal isolates cultured in 2015-16 (n = 121) and 2011 (n = 108) in Vietnam were examined. AMR testing was performed using Etest and WGS with Illumina MiSeq.\r\n\r\nResistance among the 2015-16 isolates was as follows: ciprofloxacin, 100%; tetracycline, 79%; benzylpenicillin, 50%; cefixime, 15%; ceftriaxone, 1%; spectinomycin, 0%; and 5% were non-WT to azithromycin. Eighteen (15%) isolates were MDR. The MIC range for gentamicin was 2-8 mg/L. Among the 2015-16 isolates, 27% (n = 33) contained a mosaic penA allele, while no isolates had a mosaic penA allele in 2011. Phylogenomic analysis revealed introduction after 2011 of two mosaic penA-containing clones (penA-10.001 and penA-34.001), which were related to cefixime-resistant strains spreading in Japan and Europe, and a minor clade (eight isolates) relatively similar to the XDR strain WHO Q.\r\n\r\nFrom 2011 to 2015-16, resistance in gonococci from Vietnam increased to all currently and previously used antimicrobials except ceftriaxone, spectinomycin and tetracycline. Two mosaic penA-containing clones were introduced after 2011, explaining the increased cefixime resistance. Significantly increased AMR surveillance, antimicrobial stewardship and use of WGS for molecular epidemiology and AMR prediction for gonococcal isolates in Vietnam and other Asian countries are crucial.", "doi": "10.1093/jac/dkaa040", "pmid": "32068837", "labels": {"Clinical Genomics \u00d6rebro": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "5740025"}, {"db": "pmc", "key": "PMC7382555"}], "notes": [], "created": "2020-11-27T14:03:55.802Z", "modified": "2021-12-08T12:31:02.326Z"}, {"entity": "publication", "iuid": "70b66fc8c9d14a6bbdea4ed197d9f280", "links": {"self": {"href": "https://publications.scilifelab.se/publication/70b66fc8c9d14a6bbdea4ed197d9f280.json"}, "display": {"href": "https://publications.scilifelab.se/publication/70b66fc8c9d14a6bbdea4ed197d9f280"}}, "title": "Evolutionary Analysis of the Bacillus subtilis Genome Reveals New Genes Involved in Sporulation.", "authors": [{"family": "Shi", "given": "Lei", "initials": "L"}, {"family": "Derouiche", "given": "Abderahmane", "initials": "A"}, {"family": "Pandit", "given": "Santosh", "initials": "S"}, {"family": "Rahimi", "given": "Shadi", "initials": "S"}, {"family": "Kalantari", "given": "Aida", "initials": "A"}, {"family": "Futo", "given": "Momir", "initials": "M"}, {"family": "Ravikumar", "given": "Vaishnavi", "initials": "V"}, {"family": "Jers", "given": "Carsten", "initials": "C"}, {"family": "Mokkapati", "given": "Venkata R S S", "initials": "VRSS"}, {"family": "Vlahovi\u010dek", "given": "Kristian", "initials": "K"}, {"family": "Mijakovic", "given": "Ivan", "initials": "I"}], "type": "journal article", "published": "2020-06-01", "journal": {"title": "Mol. Biol. Evol.", "issn": "1537-1719", "volume": "37", "issue": "6", "pages": "1667-1678", "issn-l": "0737-4038"}, "abstract": "Bacilli can form dormant, highly resistant, and metabolically inactive spores to cope with extreme environmental challenges. In this study, we examined the evolutionary age of Bacillus subtilis sporulation genes using the approach known as genomic phylostratigraphy. We found that B. subtilis sporulation genes cluster in several groups that emerged at distant evolutionary time-points, suggesting that the sporulation process underwent several stages of expansion. Next, we asked whether such evolutionary stratification of the genome could be used to predict involvement in sporulation of presently uncharacterized genes (y-genes). We individually inactivated a representative sample of uncharacterized genes that arose during the same evolutionary periods as the known sporulation genes and tested the resulting strains for sporulation phenotypes. Sporulation was significantly affected in 16 out of 37 (43%) tested strains. In addition to expanding the knowledge base on B. subtilis sporulation, our findings suggest that evolutionary age could be used to help with genome mining.", "doi": "10.1093/molbev/msaa035", "pmid": "32061128", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7426031"}, {"db": "pii", "key": "5736554"}], "notes": [], "created": "2023-02-16T08:08:51.363Z", "modified": "2023-02-16T08:08:51.365Z"}, {"entity": "publication", "iuid": "bdbfd05e82214b168929055fc8da1ee8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bdbfd05e82214b168929055fc8da1ee8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bdbfd05e82214b168929055fc8da1ee8"}}, "title": "The mating type system of the rare polypore Hapalopilus croceus", "authors": [{"family": "Redr", "given": "Deanne", "initials": "D"}, {"family": "Dahlberg", "given": "Anders", "initials": "A"}, {"family": "Stenlid", "given": "Jan", "initials": "J"}, {"family": "Sunhede", "given": "Stellan", "initials": "S"}, {"family": "Vasaitis", "given": "Rimvydas", "initials": "R"}, {"family": "Menkis", "given": "Audrius", "initials": "A"}], "type": "journal-article", "published": "2020-06-00", "journal": {"title": "Fungal Ecology", "issn": "1754-5048", "volume": "45", "issue": null, "pages": "100941", "issn-l": "1878-0083"}, "abstract": null, "doi": "10.1016/j.funeco.2020.100941", "pmid": null, "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service"}, "xrefs": [], "notes": [], "created": "2020-05-26T17:56:58.242Z", "modified": "2021-11-10T12:38:47.892Z"}, {"entity": "publication", "iuid": "205793144c484b22a38e28d4a971f932", "links": {"self": {"href": "https://publications.scilifelab.se/publication/205793144c484b22a38e28d4a971f932.json"}, "display": {"href": "https://publications.scilifelab.se/publication/205793144c484b22a38e28d4a971f932"}}, "title": "Size-Dependent Pulmonary Impact of Thin Graphene Oxide Sheets in Mice: Toward Safe-by-Design.", "authors": [{"family": "Rodrigues", "given": "Artur Filipe", "initials": "AF"}, {"family": "Newman", "given": "Leon", "initials": "L"}, {"family": "Jasim", "given": "Dhifaf", "initials": "D"}, {"family": "Mukherjee", "given": "Sourav P", "initials": "SP"}, {"family": "Wang", "given": "Jun", "initials": "J"}, {"family": "Vacchi", "given": "Isabella A", "initials": "IA"}, {"family": "M\u00e9nard-Moyon", "given": "C\u00e9cilia", "initials": "C"}, {"family": "Bianco", "given": "Alberto", "initials": "A"}, {"family": "Fadeel", "given": "Bengt", "initials": "B"}, {"family": "Kostarelos", "given": "Kostas", "initials": "K"}, {"family": "Bussy", "given": "Cyrill", "initials": "C", "orcid": "0000-0001-8870-443X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4b7fc372c1ae437891bd4b8e3000e281.json"}}], "type": "journal article", "published": "2020-06-00", "journal": {"title": "Adv Sci (Weinh)", "issn": "2198-3844", "volume": "7", "issue": "12", "pages": "1903200", "issn-l": null}, "abstract": "Safety assessment of graphene-based materials (GBMs) including graphene oxide (GO) is essential for their safe use across many sectors of society. In particular, the link between specific material properties and biological effects needs to be further elucidated. Here, the effects of lateral dimensions of GO sheets in acute and chronic pulmonary responses after single intranasal instillation in mice are compared. Micrometer-sized GO induces stronger pulmonary inflammation than nanometer-sized GO, despite reduced translocation to the lungs. Genome-wide RNA sequencing also reveals distinct size-dependent effects of GO, in agreement with the histopathological results. Although large GO, but not the smallest GO, triggers the formation of granulomas that persists for up to 90 days, no pulmonary fibrosis is observed. These latter results can be partly explained by Raman imaging, which evidences the progressive biotransformation of GO into less graphitic structures. The findings demonstrate that lateral dimensions play a fundamental role in the pulmonary response to GO, and suggest that airborne exposure to micrometer-sized GO should be avoided in the production plant or applications, where aerosolized dispersions are likely to occur. These results are important toward the implementation of a safer-by-design approach for GBM products and applications, for the benefit of workers and end-users.", "doi": "10.1002/advs.201903200", "pmid": "32596109", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service"}, "xrefs": [{"db": "pii", "key": "ADVS1753"}, {"db": "pmc", "key": "PMC7312279"}], "notes": [], "created": "2020-12-07T16:28:59.251Z", "modified": "2021-11-10T12:50:32.651Z"}, {"entity": "publication", "iuid": "efddda9d626548608fed72f21c6fc1dc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/efddda9d626548608fed72f21c6fc1dc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/efddda9d626548608fed72f21c6fc1dc"}}, "title": "Single-cell RNA counting at allele and isoform resolution using Smart-seq3.", "authors": [{"family": "Hagemann-Jensen", "given": "Michael", "initials": "M", "orcid": "0000-0002-6423-8216", "researcher": {"href": "https://publications.scilifelab.se/researcher/26cb45960bd042c498f4914a342312a0.json"}}, {"family": "Ziegenhain", "given": "Christoph", "initials": "C", "orcid": "0000-0003-2208-4877", "researcher": {"href": "https://publications.scilifelab.se/researcher/3297f21f1a174cd388ac586eda2b5177.json"}}, {"family": "Chen", "given": "Ping", "initials": "P"}, {"family": "Ramsk\u00f6ld", "given": "Daniel", "initials": "D", "orcid": "0000-0003-2892-673X", "researcher": {"href": "https://publications.scilifelab.se/researcher/cc367f2adb7c4379b7dc441be34e7ded.json"}}, {"family": "Hendriks", "given": "Gert-Jan", "initials": "GJ"}, {"family": "Larsson", "given": "Anton J M", "initials": "AJM"}, {"family": "Faridani", "given": "Omid R", "initials": "OR"}, {"family": "Sandberg", "given": "Rickard", "initials": "R", "orcid": "0000-0001-6473-1740", "researcher": {"href": "https://publications.scilifelab.se/researcher/048c7c9b9edb4366bac7873daad461cd.json"}}], "type": "journal article", "published": "2020-06-00", "journal": {"volume": "38", "issn": "1546-1696", "issue": "6", "pages": "708-714", "title": "Nat. Biotechnol.", "issn-l": "1087-0156"}, "abstract": "Large-scale sequencing of RNA from individual cells can reveal patterns of gene, isoform and allelic expression across cell types and states1. However, current short-read single-cell RNA-sequencing methods have limited ability to count RNAs at allele and isoform resolution, and long-read sequencing techniques lack the depth required for large-scale applications across cells2,3. Here we introduce Smart-seq3, which combines full-length transcriptome coverage with a 5' unique molecular identifier RNA counting strategy that enables in silico reconstruction of thousands of RNA molecules per cell. Of the counted and reconstructed molecules, 60% could be directly assigned to allelic origin and 30-50% to specific isoforms, and we identified substantial differences in isoform usage in different mouse strains and human cell types. Smart-seq3 greatly increased sensitivity compared to Smart-seq2, typically detecting thousands more transcripts per cell. We expect that Smart-seq3 will enable large-scale characterization of cell types and states across tissues and organisms.", "doi": "10.1038/s41587-020-0497-0", "pmid": "32518404", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41587-020-0497-0"}], "notes": [], "created": "2020-05-26T09:06:10.857Z", "modified": "2021-11-10T12:50:33.905Z"}, {"entity": "publication", "iuid": "e81411b4717b4690acc189ae0314d13d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e81411b4717b4690acc189ae0314d13d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e81411b4717b4690acc189ae0314d13d"}}, "title": "Predicting and elucidating the etiology of fatty liver disease: A machine learning modeling and validation study in the IMI DIRECT cohorts.", "authors": [{"family": "Atabaki-Pasdar", "given": "Naeimeh", "initials": "N", "orcid": "0000-0001-7229-1888", "researcher": {"href": "https://publications.scilifelab.se/researcher/42005ff304fd4e5d855a248db59f9256.json"}}, {"family": "Ohlsson", "given": "Mattias", "initials": "M", "orcid": "0000-0003-1145-4297", "researcher": {"href": "https://publications.scilifelab.se/researcher/6550861766f14999b5059457fed37baa.json"}}, {"family": "Vi\u00f1uela", "given": "Ana", "initials": "A", "orcid": "0000-0003-3771-8537", "researcher": {"href": "https://publications.scilifelab.se/researcher/e6551fc3132f4fa597378c565247a315.json"}}, {"family": "Frau", "given": "Francesca", "initials": "F"}, {"family": "Pomares-Millan", "given": "Hugo", "initials": "H", "orcid": "0000-0001-9245-4576", "researcher": {"href": "https://publications.scilifelab.se/researcher/3a53517766c64538876c42890911aed7.json"}}, {"family": "Haid", "given": "Mark", "initials": "M", "orcid": "0000-0001-6118-1333", "researcher": {"href": "https://publications.scilifelab.se/researcher/a51bbc9e2ca34b75ba75e6b3be85da87.json"}}, {"family": "Jones", "given": "Angus G", "initials": "AG", "orcid": "0000-0002-0883-7599", "researcher": {"href": "https://publications.scilifelab.se/researcher/e61710036445440ea18c4cc05bbd8a0b.json"}}, {"family": "Thomas", "given": "E Louise", "initials": "EL", "orcid": "0000-0003-4235-4694", "researcher": {"href": "https://publications.scilifelab.se/researcher/186f6dee4a8a4e199e519199a62d4918.json"}}, {"family": "Koivula", "given": "Robert W", "initials": "RW", "orcid": "0000-0002-1646-4163", "researcher": {"href": "https://publications.scilifelab.se/researcher/29fa233507ea4e6190e70953cbb743a8.json"}}, {"family": "Kurbasic", "given": "Azra", "initials": "A", "orcid": "0000-0002-1910-2619", "researcher": {"href": "https://publications.scilifelab.se/researcher/64a6b0e38fdc43f59725c6013e9ffd75.json"}}, {"family": "Mutie", "given": "Pascal M", "initials": "PM"}, {"family": "Fitipaldi", "given": "Hugo", "initials": "H", "orcid": "0000-0001-5352-2134", "researcher": {"href": "https://publications.scilifelab.se/researcher/ca2f9fb4ba1a42c59104097626568a97.json"}}, {"family": "Fernandez", "given": "Juan", "initials": "J"}, {"family": "Dawed", "given": "Adem Y", "initials": "AY", "orcid": "0000-0003-0224-2428", "researcher": {"href": "https://publications.scilifelab.se/researcher/a1b08d70569c4ee98f6b174425a443a7.json"}}, {"family": "Giordano", "given": "Giuseppe N", "initials": "GN"}, {"family": "Forgie", "given": "Ian M", "initials": "IM", "orcid": "0000-0002-8800-6145", "researcher": {"href": "https://publications.scilifelab.se/researcher/bcf5280c81274cb3b983c00b20fbd0a7.json"}}, {"family": "McDonald", "given": "Timothy J", "initials": "TJ"}, {"family": "Rutters", "given": "Femke", "initials": "F"}, {"family": "Cederberg", "given": "Henna", "initials": "H", "orcid": "0000-0003-2901-9373", "researcher": {"href": "https://publications.scilifelab.se/researcher/64ab64bd196c4dc88904a53826dda0e1.json"}}, {"family": "Chabanova", "given": "Elizaveta", "initials": "E"}, {"family": "Dale", "given": "Matilda", "initials": "M", "orcid": "0000-0002-5788-7744", "researcher": {"href": "https://publications.scilifelab.se/researcher/59306e7e902048829efb30599ee3d2b1.json"}}, {"family": "Masi", "given": "Federico De", "initials": "F", "orcid": "0000-0003-4859-4170", "researcher": {"href": "https://publications.scilifelab.se/researcher/fb3d84bde37b4deb8838eb7b95762832.json"}}, {"family": "Thomas", "given": "Cecilia Engel", "initials": "CE", "orcid": "0000-0001-6201-6380", "researcher": {"href": "https://publications.scilifelab.se/researcher/3a1156f987764218af202efbd76c31fd.json"}}, {"family": "Allin", "given": "Kristine H", "initials": "KH", "orcid": "0000-0002-6880-5759", "researcher": {"href": "https://publications.scilifelab.se/researcher/3b7436fd7201456d9555235679ad0aa3.json"}}, {"family": "Hansen", "given": "Tue H", "initials": "TH", "orcid": "0000-0001-5948-8993", "researcher": {"href": "https://publications.scilifelab.se/researcher/c43c49838ac04c30ac2d92153e51f555.json"}}, {"family": "Heggie", "given": "Alison", "initials": "A"}, {"family": "Hong", "given": "Mun-Gwan", "initials": "MG"}, {"family": "Elders", "given": "Petra J M", "initials": "PJM", "orcid": "0000-0002-5907-7219", "researcher": {"href": "https://publications.scilifelab.se/researcher/4cf5e762102f4cc6a669b6d0989ab3a1.json"}}, {"family": "Kennedy", "given": "Gwen", "initials": "G", "orcid": "0000-0002-9856-3236", "researcher": {"href": "https://publications.scilifelab.se/researcher/28563ecc468548a4a75f127ffd3ab61b.json"}}, {"family": "Kokkola", "given": "Tarja", "initials": "T", "orcid": "0000-0002-3303-3912", "researcher": {"href": "https://publications.scilifelab.se/researcher/fa456d442a7342238959b8ee46310319.json"}}, {"family": "Pedersen", "given": "Helle Krogh", "initials": "HK", "orcid": "0000-0001-9609-7377", "researcher": {"href": "https://publications.scilifelab.se/researcher/ad86129a6eec49f1b0fe4ce09643c8a1.json"}}, {"family": "Mahajan", "given": "Anubha", "initials": "A", "orcid": "0000-0001-5585-3420", "researcher": {"href": "https://publications.scilifelab.se/researcher/194be8a851164e2ea4d004dd2febc9be.json"}}, {"family": "McEvoy", "given": "Donna", "initials": "D", "orcid": "0000-0003-1546-5567", "researcher": {"href": "https://publications.scilifelab.se/researcher/c4455f5ace534325ba30494630686066.json"}}, {"family": "Pattou", "given": "Francois", "initials": "F"}, {"family": "Raverdy", "given": "Violeta", "initials": "V"}, {"family": "H\u00e4ussler", "given": "Ragna S", "initials": "RS", "orcid": "0000-0003-1664-8875", "researcher": {"href": "https://publications.scilifelab.se/researcher/ca04d9b9132747efb7db0efb6e34756a.json"}}, {"family": "Sharma", "given": "Sapna", "initials": "S"}, {"family": "Thomsen", "given": "Henrik S", "initials": "HS"}, {"family": "Vangipurapu", "given": "Jagadish", "initials": "J", "orcid": "0000-0001-6657-2659", "researcher": {"href": "https://publications.scilifelab.se/researcher/cc3c64aafa4841729040479765aae6f2.json"}}, {"family": "Vestergaard", "given": "Henrik", "initials": "H", "orcid": "0000-0003-3090-269X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a79ddd7842e480f85b0a303125fdc9a.json"}}, {"family": "'t Hart", "given": "Leen M", "initials": "LM", "orcid": "0000-0003-4401-2938", "researcher": {"href": "https://publications.scilifelab.se/researcher/3cb1193c2ad3419899ec86d9d95bf25d.json"}}, {"family": "Adamski", "given": "Jerzy", "initials": "J"}, {"family": "Musholt", "given": "Petra B", "initials": "PB"}, {"family": "Brage", "given": "Soren", "initials": "S", "orcid": "0000-0002-1265-7355", "researcher": {"href": "https://publications.scilifelab.se/researcher/2edeab82aa9f4513baa3dc724c0a4a88.json"}}, {"family": "Brunak", "given": "S\u00f8ren", "initials": "S"}, {"family": "Dermitzakis", "given": "Emmanouil", "initials": "E"}, {"family": "Frost", "given": "Gary", "initials": "G", "orcid": "0000-0003-0529-6325", "researcher": {"href": "https://publications.scilifelab.se/researcher/b9312f44496b4bdb86ad9c5096aeb94c.json"}}, {"family": "Hansen", "given": "Torben", "initials": "T", "orcid": "0000-0001-8748-3831", "researcher": {"href": "https://publications.scilifelab.se/researcher/da403496660346079fc41975cae418d9.json"}}, {"family": "Laakso", "given": "Markku", "initials": "M"}, {"family": "Pedersen", "given": "Oluf", "initials": "O"}, {"family": "Ridderstr\u00e5le", "given": "Martin", "initials": "M"}, {"family": "Ruetten", "given": "Hartmut", "initials": "H"}, {"family": "Hattersley", "given": "Andrew T", "initials": "AT", "orcid": "0000-0001-5620-473X", "researcher": {"href": "https://publications.scilifelab.se/researcher/25dad832cfe041a79e35170e789e66c7.json"}}, {"family": "Walker", "given": "Mark", "initials": "M"}, {"family": "Beulens", "given": "Joline W J", "initials": "JWJ"}, {"family": "Mari", "given": "Andrea", "initials": "A", "orcid": "0000-0002-1436-5591", "researcher": {"href": "https://publications.scilifelab.se/researcher/c8b959c8980a4d108b602d82cd345ba6.json"}}, {"family": "Schwenk", "given": "Jochen M", "initials": "JM", "orcid": "0000-0001-8141-8449", "researcher": {"href": "https://publications.scilifelab.se/researcher/aba5822711b246b397fffacb7ae403b3.json"}}, {"family": "Gupta", "given": "Ramneek", "initials": "R", "orcid": "0000-0001-6841-6676", "researcher": {"href": "https://publications.scilifelab.se/researcher/445ec9fcd4a740a385550d10d19e8317.json"}}, {"family": "McCarthy", "given": "Mark I", "initials": "MI", "orcid": "0000-0002-4393-0510", "researcher": {"href": "https://publications.scilifelab.se/researcher/5e44f4b1ca3a49cb8f83450ef9482e91.json"}}, {"family": "Pearson", "given": "Ewan R", "initials": "ER", "orcid": "0000-0001-9237-8585", "researcher": {"href": "https://publications.scilifelab.se/researcher/320eb6ae20014620ad8f69c3f7b216b3.json"}}, {"family": "Bell", "given": "Jimmy D", "initials": "JD", "orcid": "0000-0003-3804-1281", "researcher": {"href": "https://publications.scilifelab.se/researcher/74a9ddf1d40e4b4fb1614a89a220e143.json"}}, {"family": "Pavo", "given": "Imre", "initials": "I"}, {"family": "Franks", "given": "Paul W", "initials": "PW", "orcid": "0000-0002-0520-7604", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ebbf40c0f7e49dd8c75a2b6cbf27276.json"}}], "type": "journal article", "published": "2020-06-00", "journal": {"title": "PLoS Med.", "issn": "1549-1676", "issn-l": "1549-1277", "volume": "17", "issue": "6", "pages": "e1003149"}, "abstract": "Non-alcoholic fatty liver disease (NAFLD) is highly prevalent and causes serious health complications in individuals with and without type 2 diabetes (T2D). Early diagnosis of NAFLD is important, as this can help prevent irreversible damage to the liver and, ultimately, hepatocellular carcinomas. We sought to expand etiological understanding and develop a diagnostic tool for NAFLD using machine learning.\n\nWe utilized the baseline data from IMI DIRECT, a multicenter prospective cohort study of 3,029 European-ancestry adults recently diagnosed with T2D (n = 795) or at high risk of developing the disease (n = 2,234). Multi-omics (genetic, transcriptomic, proteomic, and metabolomic) and clinical (liver enzymes and other serological biomarkers, anthropometry, measures of beta-cell function, insulin sensitivity, and lifestyle) data comprised the key input variables. The models were trained on MRI-image-derived liver fat content (<5% or \u22655%) available for 1,514 participants. We applied LASSO (least absolute shrinkage and selection operator) to select features from the different layers of omics data and random forest analysis to develop the models. The prediction models included clinical and omics variables separately or in combination. A model including all omics and clinical variables yielded a cross-validated receiver operating characteristic area under the curve (ROCAUC) of 0.84 (95% CI 0.82, 0.86; p < 0.001), which compared with a ROCAUC of 0.82 (95% CI 0.81, 0.83; p < 0.001) for a model including 9 clinically accessible variables. The IMI DIRECT prediction models outperformed existing noninvasive NAFLD prediction tools. One limitation is that these analyses were performed in adults of European ancestry residing in northern Europe, and it is unknown how well these findings will translate to people of other ancestries and exposed to environmental risk factors that differ from those of the present cohort. Another key limitation of this study is that the prediction was done on a binary outcome of liver fat quantity (<5% or \u22655%) rather than a continuous one.\n\nIn this study, we developed several models with different combinations of clinical and omics data and identified biological features that appear to be associated with liver fat accumulation. In general, the clinical variables showed better prediction ability than the complex omics variables. However, the combination of omics and clinical variables yielded the highest accuracy. We have incorporated the developed clinical models into a web interface (see: https://www.predictliverfat.org/) and made it available to the community.\n\nClinicalTrials.gov NCT03814915.", "doi": "10.1371/journal.pmed.1003149", "pmid": "32559194", "labels": {"Affinity Proteomics Stockholm": "Collaborative"}, "xrefs": [{"db": "pii", "key": "PMEDICINE-D-20-00136"}, {"db": "pmc", "key": "PMC7304567"}, {"db": "ClinicalTrials.gov", "key": "NCT03814915"}], "notes": [], "created": "2020-12-10T19:03:48.331Z", "modified": "2021-11-10T12:50:35.188Z"}, {"entity": "publication", "iuid": "1e8306e370e24ba5acf2c1cba73120c4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1e8306e370e24ba5acf2c1cba73120c4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1e8306e370e24ba5acf2c1cba73120c4"}}, "title": "Normal Testosterone but Higher Luteinizing Hormone Plasma Levels in Men With Hypersexual Disorder.", "authors": [{"family": "Chatzittofis", "given": "Andreas", "initials": "A"}, {"family": "Bostr\u00f6m", "given": "Adrian E", "initials": "AE"}, {"family": "\u00d6berg", "given": "Katarina G\u00f6rts", "initials": "KG"}, {"family": "Flanagan", "given": "John N", "initials": "JN"}, {"family": "Schi\u00f6th", "given": "Helgi B", "initials": "HB"}, {"family": "Arver", "given": "Stefan", "initials": "S"}, {"family": "Jokinen", "given": "Jussi", "initials": "J"}], "type": "journal article", "published": "2020-06-00", "journal": {"volume": "8", "issn": "2050-1161", "issue": "2", "pages": "243-250", "title": "Sex Med", "issn-l": "2050-1161"}, "abstract": "Hypersexual disorder as suggested to be included in the Diagnostic and Statistical Manual of Mental Disorders-5 integrates aspects of sexual desire deregulation, impulsivity, and compulsivity. However, it is unknown how it affects gonadal activity and the function of the hypothalamus-pituitary-gonadal (HPG) axis.\n\nThe aim of this study was to investigate testosterone and luteinizing hormone (LH) levels in hypersexual men compared with healthy controls. Furthermore, we investigated associations between epigenetic markers and hormone levels.\n\nBasal morning plasma levels of testosterone, LH, and sex hormone-binding globulin (SHBG) were assessed in 67 hypersexual men (mean age: 39.2 years) compared with 39 age-matched healthy controls (mean age: 37.5 years). The Sexual Compulsivity Scale and the Hypersexual Disorder: Current Assessment Scale were used for assessing hypersexual behavior, the Montgomery-\u00c5sberg Depression Scale-self rating was used for depression severity, and the Childhood Trauma Questionnaire (CTQ) was used for assessing history of childhood adversity. The genome-wide methylation pattern of more than 850 K CpG sites was measured in whole blood using the Illumina Infinium Methylation EPIC BeadChip. CpG sites located within 2,000 bp of the transcriptional start site of hypothalamus pituitary adrenal (HPA) and HPG axis-coupled genes were included.\n\nTestosterone and LH plasma levels in association with clinical rating and a secondary outcome was the epigenetic profile of HPA and HPG axis-coupled CpG sites with testosterone and LH levels.\n\nLH plasma levels were significantly higher in patients with hypersexual disorder than in healthy volunteers. No significant differences in plasma testosterone, follicle stimulating hormone, prolactin, and SHBG levels were found between the groups. There were no significant associations between DNA methylation of HPA and HPG axis-coupled genes and plasma testosterone or LH levels after multiple testing corrections.\n\nSubtle dysregulation of the HPG axis, with increased LH plasma levels but no difference in testosterone levels may be present in hypersexual men. Chatzittofis A, Bostr\u00f6m AE, \u00d6berg KG, et al. Normal Testosterone but Higher Luteinizing Hormone Plasma Levels in Men With Hypersexual Disorder. Sex Med 2020;8:243-250.", "doi": "10.1016/j.esxm.2020.02.005", "pmid": "32173350", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "S2050-1161(20)30028-3"}, {"db": "pmc", "key": "PMC7261685"}], "notes": [], "created": "2020-06-09T14:54:10.628Z", "modified": "2021-11-10T12:50:36.262Z"}, {"entity": "publication", "iuid": "b3a7f3df17924aff80c6d32b2f8dad0e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b3a7f3df17924aff80c6d32b2f8dad0e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b3a7f3df17924aff80c6d32b2f8dad0e"}}, "title": "New approaches to the study of immune responses in humans.", "authors": [{"family": "Brodin", "given": "Petter", "initials": "P", "orcid": "0000-0002-8103-0046", "researcher": {"href": "https://publications.scilifelab.se/researcher/40097353cdb24e52bf2330eb687042bf.json"}}], "type": "journal article", "published": "2020-06-00", "journal": {"volume": "139", "issn": "1432-1203", "issue": "6-7", "pages": "795-799", "title": "Hum. Genet.", "issn-l": "0340-6717"}, "abstract": "The human immune system consists of multiple, layered mechanisms of sensing and responding to cellular stress, infection and tissue damage to ensure defense from pathogens, maintenance of tissue homeostasis, and the integrity of the holobiont. Every single cell in the body has a role to play, but a few dozen, specialized white blood cells are particularly important in this respect. Understanding the overall state of this multifaceted system in a single individual is challenging, and we are only beginning to do this across populations of individuals, to understand the vast range of inter-individual variation, and the influences of genes and environmental factors that collectively shape the immune system in a given individual. We are also only beginning to understand the changes occurring within this system over time, and how this relates to health and disease susceptibility. Several technological breakthroughs in recent years have enabled these developments and the emergence of a new, complementary approach to studying human immune systems, namely systems immunology. In this paradigm, the focus is shifted from the understanding of individual immune system components and their mechanisms of action, towards analyses of cell-cell interactions, and mechanisms of coordination and regulation within the human immune system.", "doi": "10.1007/s00439-020-02129-3", "pmid": "32040614", "labels": {"Cellular Immunomonitoring": "Technology development"}, "xrefs": [{"db": "pii", "key": "10.1007/s00439-020-02129-3"}, {"db": "pmc", "key": "PMC7272481"}], "notes": [], "created": "2020-02-11T12:26:35.626Z", "modified": "2021-11-10T12:50:37.339Z"}, {"entity": "publication", "iuid": "47c327c6229e475bad4889ad53a15767", "links": {"self": {"href": "https://publications.scilifelab.se/publication/47c327c6229e475bad4889ad53a15767.json"}, "display": {"href": "https://publications.scilifelab.se/publication/47c327c6229e475bad4889ad53a15767"}}, "title": "Mitochondrial genomes from Bronze Age Poland reveal genetic continuity from the Late Neolithic and additional genetic affinities with the steppe populations.", "authors": [{"family": "Juras", "given": "Anna", "initials": "A", "orcid": "0000-0002-2585-127X", "researcher": {"href": "https://publications.scilifelab.se/researcher/21890fe291bb4e8e913c5eb5963bcdce.json"}}, {"family": "Makarowicz", "given": "Przemys\u0142aw", "initials": "P"}, {"family": "Chyle\u0144ski", "given": "Maciej", "initials": "M"}, {"family": "Ehler", "given": "Edvard", "initials": "E", "orcid": "0000-0003-1774-0091", "researcher": {"href": "https://publications.scilifelab.se/researcher/6d5e30a4e46e47d8b800d5242e23d7de.json"}}, {"family": "Malmstr\u00f6m", "given": "Helena", "initials": "H"}, {"family": "Krzewi\u0144ska", "given": "Maja", "initials": "M"}, {"family": "Pospieszny", "given": "\u0141ukasz", "initials": "\u0141"}, {"family": "G\u00f3rski", "given": "Jacek", "initials": "J"}, {"family": "Taras", "given": "Halina", "initials": "H"}, {"family": "Szczepanek", "given": "Anita", "initials": "A"}, {"family": "Pola\u0144ska", "given": "Marta", "initials": "M"}, {"family": "W\u0142odarczak", "given": "Piotr", "initials": "P"}, {"family": "Szyca", "given": "Agnieszka", "initials": "A"}, {"family": "Lasota-Ku\u015b", "given": "Anna", "initials": "A"}, {"family": "W\u00f3jcik", "given": "Irena", "initials": "I"}, {"family": "Jakobsson", "given": "Mattias", "initials": "M", "orcid": "0000-0001-7840-7853", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a4abe0fcb20492d9ec849c9fbf58a71.json"}}, {"family": "Dabert", "given": "Miroslawa", "initials": "M"}], "type": "historical article", "published": "2020-06-00", "journal": {"title": "Am. J. Phys. Anthropol.", "issn": "1096-8644", "volume": "172", "issue": "2", "pages": "176-188", "issn-l": "0002-9483"}, "abstract": "In this work we aim to investigate the origins and genetic affinities of Bronze Age populations (2,400-1,100 BC) from the region of southern Poland and to trace maternal kinship patterns present in the burials of those populations by the use of complete mitochondrial genomes.\n\nWe performed ancient DNA analyses for Bronze Age individuals from present-day Poland associated with the Strzy\u017cow culture, the Mierzanowice culture, and the Trzciniec Cultural circle. To obtain complete mitochondrial genomes, we sequenced genomic libraries using Illumina platform. Additionally, hybridization capture was used to enrich some of the samples for mitochondrial DNA. AMS 14 C-dating was conducted for 51 individuals to verify chronological and cultural attribution of the analyzed samples.\n\nComplete ancient mitochondrial genomes were generated for 80 of the Bronze Age individuals from present-day Poland. The results of the population genetic analyses indicate close maternal genetic affinity between Mierzanowice, Trzciniec, and Corded Ware culture-associated populations. This is in contrast to the genetically more distant Strzy\u017c\u00f3w people that displayed closer maternal genetic relation to steppe populations associated with the preceding Yamnaya culture and Catacomb culture, and with later Scythians. Potential maternal kinship relations were identified in burials of Mierzanowice and Trzciniec populations analyzed in this study.\n\nResults revealed genetic continuity from the Late Neolithic Corded Ware groups to Bronze Age Mierzanowice and Trzciniec-associated populations, and possible additional genetic contribution from the steppe to the formation of the Strzy\u017c\u00f3w-associated group at the end of 3rd millennium BC. Mitochondrial patterns indicated several pairs of potentially maternally related individuals mostly in Trzciniec-associated group.", "doi": "10.1002/ajpa.24057", "pmid": "32297323", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [], "notes": [], "created": "2020-12-08T23:25:04.935Z", "modified": "2024-01-16T13:48:42.437Z"}, {"entity": "publication", "iuid": "4ecd17a8696c4be1ae504f4babcfed98", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4ecd17a8696c4be1ae504f4babcfed98.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4ecd17a8696c4be1ae504f4babcfed98"}}, "title": "MYO5B mutations in pheochromocytoma/paraganglioma promote cancer progression.", "authors": [{"family": "Tomi\u0107", "given": "Tajana Te\u0161an", "initials": "TT"}, {"family": "Olausson", "given": "Josefin", "initials": "J", "orcid": "0000-0003-0171-2619", "researcher": {"href": "https://publications.scilifelab.se/researcher/2a145d6088d640c8a58075cc23b365d5.json"}}, {"family": "Rehammar", "given": "Anna", "initials": "A", "orcid": "0000-0002-8597-9160", "researcher": {"href": "https://publications.scilifelab.se/researcher/c40450e7a674468799df4d6664fb8c2e.json"}}, {"family": "Deland", "given": "Lily", "initials": "L"}, {"family": "Muth", "given": "Andreas", "initials": "A", "orcid": "0000-0003-0857-1521", "researcher": {"href": "https://publications.scilifelab.se/researcher/025b271eff4c4c5d922664934912cd8c.json"}}, {"family": "Ejesk\u00e4r", "given": "Katarina", "initials": "K", "orcid": "0000-0001-8962-0860", "researcher": {"href": "https://publications.scilifelab.se/researcher/9c79e724c1954cf39f5511f7a6021513.json"}}, {"family": "Nilsson", "given": "Staffan", "initials": "S"}, {"family": "Kristiansson", "given": "Erik", "initials": "E"}, {"family": "Wass\u00e9n", "given": "Ola Nilsson", "initials": "ON"}, {"family": "Abel", "given": "Frida", "initials": "F", "orcid": "0000-0001-6958-4487", "researcher": {"href": "https://publications.scilifelab.se/researcher/957445dd84024bac8cc6b1cca2f07473.json"}}], "type": "journal article", "published": "2020-06-00", "journal": {"title": "PLoS Genet.", "issn": "1553-7404", "volume": "16", "issue": "6", "pages": "e1008803", "issn-l": "1553-7390"}, "abstract": "Identification of additional cancer-associated genes and secondary mutations driving the metastatic progression in pheochromocytoma and paraganglioma (PPGL) is important for subtyping, and may provide optimization of therapeutic regimens. We recently reported novel recurrent nonsynonymous mutations in the MYO5B gene in metastatic PPGL. Here, we explored the functional impact of these MYO5B mutations, and analyzed MYO5B expression in primary PPGL tumor cases in relation to mutation status. Immunohistochemistry and mRNA expression analysis in 30 PPGL tumors revealed an increased MYO5B expression in metastatic compared to non-metastatic cases. In addition, subcellular localization of MYO5B protein was altered from cytoplasmic to membranous in some metastatic tumors, and the strongest and most abnormal expression pattern was observed in a paraganglioma harboring a somatic MYO5B:p.G1611S mutation. In addition to five previously discovered MYO5B mutations, the present study of 30 PPGL (8 previous and 22 new samples) also revealed two, and hence recurrent, mutations in the gene paralog MYO5A. The three MYO5B missense mutations with the highest prediction scores (p.L587P, p.G1611S and p.R1641C) were selected and functionally validated using site directed mutagenesis and stable transfection into human neuroblastoma cells (SK-N-AS) and embryonic kidney cells (HEK293). In vitro analysis showed a significant increased proliferation rate in all three MYO5B mutated clones. The two somatically derived mutations, p.L587P and p.G1611S, were also found to increase the migration rate. Expression analysis of MYO5B mutants compared to wild type clones, demonstrated a significant enrichment of genes involved in migration, proliferation, cell adhesion, glucose metabolism, and cellular homeostasis. Our study validates the functional role of novel MYO5B mutations in proliferation and migration, and suggest the MYO5-pathway to be involved in the malignant progression in some PPGL tumors.", "doi": "10.1371/journal.pgen.1008803", "pmid": "32511227", "labels": {"Clinical Genomics Gothenburg": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "PGENETICS-D-19-01340"}, {"db": "pmc", "key": "PMC7329139"}], "notes": [], "created": "2022-03-29T13:40:03.999Z", "modified": "2022-03-29T13:40:04.183Z"}, {"entity": "publication", "iuid": "b77ba73fb7c241d09a2734a4ef5e2832", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b77ba73fb7c241d09a2734a4ef5e2832.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b77ba73fb7c241d09a2734a4ef5e2832"}}, "title": "Genome-wide CRISPR screen identifies ZIC2 as an essential gene that controls the cell fate of early mesodermal precursors to human heart progenitors.", "authors": [{"family": "Xu", "given": "Jiejia", "initials": "J", "orcid": "0000-0003-3885-3546", "researcher": {"href": "https://publications.scilifelab.se/researcher/144d8f8036b34c4f964c67255449c7a5.json"}}, {"family": "Zhou", "given": "Chikai", "initials": "C"}, {"family": "Foo", "given": "Kylie S", "initials": "KS"}, {"family": "Yang", "given": "Ran", "initials": "R"}, {"family": "Xiao", "given": "Yao", "initials": "Y"}, {"family": "Bylund", "given": "Kristine", "initials": "K"}, {"family": "Sahara", "given": "Makoto", "initials": "M"}, {"family": "Chien", "given": "Kenneth R", "initials": "KR"}], "type": "journal article", "published": "2020-06-00", "journal": {"title": "Stem Cells", "issn": "1549-4918", "volume": "38", "issue": "6", "pages": "741-755", "issn-l": "1066-5099"}, "abstract": "Cardiac progenitor formation is one of the earliest committed steps of human cardiogenesis and requires the cooperation of multiple gene sets governed by developmental signaling cascades. To determine the key regulators for cardiac progenitor formation, we have developed a two-stage genome-wide CRISPR-knockout screen. We mimicked the progenitor formation process by differentiating human pluripotent stem cells (hPSCs) into cardiomyocytes, monitored by two distinct stage markers of early cardiac mesodermal formation and commitment to a multipotent heart progenitor cell fate: MESP1 and ISL1, respectively. From the screen output, we compiled a list of 15 candidate genes. After validating seven of them, we identified ZIC2 as an essential gene for cardiac progenitor formation. ZIC2 is known as a master regulator of neurogenesis. hPSCs with ZIC2 mutated still express pluripotency markers. However, their ability to differentiate into cardiomyocytes was greatly attenuated. RNA-Seq profiling of the ZIC2-mutant cells revealed that the mutants switched their cell fate alternatively to the noncardiac cell lineage. Further, single cell RNA-seq analysis showed the ZIC2 mutants affected the apelin receptor-related signaling pathway during mesoderm formation. Our results provide a new link between ZIC2 and human cardiogenesis and document the potential power of a genome-wide unbiased CRISPR-knockout screen to identify the key steps in human mesoderm precursor cell- and heart progenitor cell-fate determination during in vitro hPSC cardiogenesis.", "doi": "10.1002/stem.3168", "pmid": "32129551", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7891398"}], "notes": [], "created": "2020-07-08T13:05:12.225Z", "modified": "2024-01-16T13:48:42.444Z"}, {"entity": "publication", "iuid": "03e3bbe957834896bd6e68663e072109", "links": {"self": {"href": "https://publications.scilifelab.se/publication/03e3bbe957834896bd6e68663e072109.json"}, "display": {"href": "https://publications.scilifelab.se/publication/03e3bbe957834896bd6e68663e072109"}}, "title": "DEqMS: A Method for Accurate Variance Estimation in Differential Protein Expression Analysis.", "authors": [{"family": "Zhu", "given": "Yafeng", "initials": "Y"}, {"family": "Orre", "given": "Lukas M", "initials": "LM", "orcid": "0000-0002-0384-1003", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b4e49a93b0143db88059c4d1e9fdc59.json"}}, {"family": "Zhou Tran", "given": "Yan", "initials": "Y"}, {"family": "Mermelekas", "given": "Georgios", "initials": "G"}, {"family": "Johansson", "given": "Henrik J", "initials": "HJ"}, {"family": "Malyutina", "given": "Alina", "initials": "A"}, {"family": "Anders", "given": "Simon", "initials": "S", "orcid": "0000-0003-4868-1805", "researcher": {"href": "https://publications.scilifelab.se/researcher/c11e0cc8bbb846ac821dcd782024c0cc.json"}}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}], "type": "journal article", "published": "2020-06-00", "journal": {"title": "Mol. Cell Proteomics", "issn": "1535-9484", "volume": "19", "issue": "6", "pages": "1047-1057", "issn-l": "1535-9476"}, "abstract": "Quantitative proteomics by mass spectrometry is widely used in biomarker research and basic biology research for investigation of phenotype level cellular events. Despite the wide application, the methodology for statistical analysis of differentially expressed proteins has not been unified. Various methods such as t test, linear model and mixed effect models are used to define changes in proteomics experiments. However, none of these methods consider the specific structure of MS-data. Choices between methods, often originally developed for other types of data, are based on compromises between features such as statistical power, general applicability and user friendliness. Furthermore, whether to include proteins identified with one peptide in statistical analysis of differential protein expression varies between studies. Here we present DEqMS, a robust statistical method developed specifically for differential protein expression analysis in mass spectrometry data. In all data sets investigated there is a clear dependence of variance on the number of PSMs or peptides used for protein quantification. DEqMS takes this feature into account when assessing differential protein expression. This allows for a more accurate data-dependent estimation of protein variance and inclusion of single peptide identifications without increasing false discoveries. The method was tested in several data sets including E. coli proteome spike-in data, using both label-free and TMT-labeled quantification. Compared with previous statistical methods used in quantitative proteomics, DEqMS showed consistently better accuracy in detecting altered protein levels compared with other statistical methods in both label-free and labeled quantitative proteomics data. DEqMS is available as an R package in Bioconductor.", "doi": "10.1074/mcp.TIR119.001646", "pmid": "32205417", "labels": {"Global Proteomics and Proteogenomics": "Technology development"}, "xrefs": [{"db": "pii", "key": "S1535-9476(20)34997-5"}, {"db": "pmc", "key": "PMC7261819"}], "notes": [], "created": "2021-01-12T18:14:40.770Z", "modified": "2021-11-10T12:50:41.761Z"}, {"entity": "publication", "iuid": "ed70a147175843f5a31852a576f105bc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ed70a147175843f5a31852a576f105bc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ed70a147175843f5a31852a576f105bc"}}, "title": "Benchmarking single-cell RNA-sequencing protocols for cell atlas projects.", "authors": [{"family": "Mereu", "given": "Elisabetta", "initials": "E"}, {"family": "Lafzi", "given": "Atefeh", "initials": "A"}, {"family": "Moutinho", "given": "Catia", "initials": "C"}, {"family": "Ziegenhain", "given": "Christoph", "initials": "C", "orcid": "0000-0003-2208-4877", "researcher": {"href": "https://publications.scilifelab.se/researcher/3297f21f1a174cd388ac586eda2b5177.json"}}, {"family": "McCarthy", "given": "Davis J", "initials": "DJ"}, {"family": "\u00c1lvarez-Varela", "given": "Adri\u00e1n", "initials": "A"}, {"family": "Batlle", "given": "Eduard", "initials": "E"}, {"family": "Gr\u00fcn", "given": "Dominic", "initials": "D", "orcid": "0000-0002-3364-5898", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ee67aea7fd94e56a66d33a92c32863b.json"}}, {"family": "Lau", "given": "Julia K", "initials": "JK"}, {"family": "Boutet", "given": "St\u00e9phane C", "initials": "SC"}, {"family": "Sanada", "given": "Chad", "initials": "C"}, {"family": "Ooi", "given": "Aik", "initials": "A"}, {"family": "Jones", "given": "Robert C", "initials": "RC", "orcid": "0000-0001-7235-9854", "researcher": {"href": "https://publications.scilifelab.se/researcher/4fc0262d6f154970914dce5fa42fa83f.json"}}, {"family": "Kaihara", "given": "Kelly", "initials": "K"}, {"family": "Brampton", "given": "Chris", "initials": "C"}, {"family": "Talaga", "given": "Yasha", "initials": "Y"}, {"family": "Sasagawa", "given": "Yohei", "initials": "Y"}, {"family": "Tanaka", "given": "Kaori", "initials": "K"}, {"family": "Hayashi", "given": "Tetsutaro", "initials": "T"}, {"family": "Braeuning", "given": "Caroline", "initials": "C"}, {"family": "Fischer", "given": "Cornelius", "initials": "C", "orcid": "0000-0003-0329-2435", "researcher": {"href": "https://publications.scilifelab.se/researcher/7dcb9bf2b11a45a9a95219a0e456388e.json"}}, {"family": "Sauer", "given": "Sascha", "initials": "S"}, {"family": "Trefzer", "given": "Timo", "initials": "T"}, {"family": "Conrad", "given": "Christian", "initials": "C"}, {"family": "Adiconis", "given": "Xian", "initials": "X"}, {"family": "Nguyen", "given": "Lan T", "initials": "LT"}, {"family": "Regev", "given": "Aviv", "initials": "A", "orcid": "0000-0003-3293-3158", "researcher": {"href": "https://publications.scilifelab.se/researcher/36ee05b2a25d42769587c29b909ba9db.json"}}, {"family": "Levin", "given": "Joshua Z", "initials": "JZ", "orcid": "0000-0002-0170-3598", "researcher": {"href": "https://publications.scilifelab.se/researcher/6aab17c0401f44df98fa2df56e8ddcae.json"}}, {"family": "Parekh", "given": "Swati", "initials": "S", "orcid": "0000-0002-4826-1651", "researcher": {"href": "https://publications.scilifelab.se/researcher/aeed2ef091514d25aa845563f9c41687.json"}}, {"family": "Janjic", "given": "Aleksandar", "initials": "A", "orcid": "0000-0001-7180-5381", "researcher": {"href": "https://publications.scilifelab.se/researcher/38aaef51d88e4c6795f38fb6e8cee5d5.json"}}, {"family": "Wange", "given": "Lucas E", "initials": "LE", "orcid": "0000-0002-3275-9156", "researcher": {"href": "https://publications.scilifelab.se/researcher/9d25e9c8662444ecaad76339843df61e.json"}}, {"family": "Bagnoli", "given": "Johannes W", "initials": "JW"}, {"family": "Enard", "given": "Wolfgang", "initials": "W", "orcid": "0000-0002-4056-0550", "researcher": {"href": "https://publications.scilifelab.se/researcher/5bc85b7ab2ce48408c3d9e00895a7cbf.json"}}, {"family": "Gut", "given": "Marta", "initials": "M"}, {"family": "Sandberg", "given": "Rickard", "initials": "R", "orcid": "0000-0001-6473-1740", "researcher": {"href": "https://publications.scilifelab.se/researcher/048c7c9b9edb4366bac7873daad461cd.json"}}, {"family": "Nikaido", "given": "Itoshi", "initials": "I", "orcid": "0000-0002-7261-2570", "researcher": {"href": "https://publications.scilifelab.se/researcher/c5c5e9ef375146618fb7fbe1c95c2104.json"}}, {"family": "Gut", "given": "Ivo", "initials": "I", "orcid": "0000-0001-7219-632X", "researcher": {"href": "https://publications.scilifelab.se/researcher/c14600c4e0d54a7aae393c728d9af088.json"}}, {"family": "Stegle", "given": "Oliver", "initials": "O"}, {"family": "Heyn", "given": "Holger", "initials": "H", "orcid": "0000-0002-3276-1889", "researcher": {"href": "https://publications.scilifelab.se/researcher/b7f8103bc9af4fb5a3bd1d544648e588.json"}}], "type": "journal article", "published": "2020-06-00", "journal": {"title": "Nat. Biotechnol.", "issn": "1546-1696", "volume": "38", "issue": "6", "pages": "747-755", "issn-l": "1087-0156"}, "abstract": "Single-cell RNA sequencing (scRNA-seq) is the leading technique for characterizing the transcriptomes of individual cells in a sample. The latest protocols are scalable to thousands of cells and are being used to compile cell atlases of tissues, organs and organisms. However, the protocols differ substantially with respect to their RNA capture efficiency, bias, scale and costs, and their relative advantages for different applications are unclear. In the present study, we generated benchmark datasets to systematically evaluate protocols in terms of their power to comprehensively describe cell types and states. We performed a multicenter study comparing 13 commonly used scRNA-seq and single-nucleus RNA-seq protocols applied to a heterogeneous reference sample resource. Comparative analysis revealed marked differences in protocol performance. The protocols differed in library complexity and their ability to detect cell-type markers, impacting their predictive value and suitability for integration into reference cell atlases. These results provide guidance both for individual researchers and for consortium projects such as the Human Cell Atlas.", "doi": "10.1038/s41587-020-0469-4", "pmid": "32518403", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41587-020-0469-4"}], "notes": [], "created": "2020-07-08T13:04:12.225Z", "modified": "2021-11-10T12:50:42.946Z"}, {"entity": "publication", "iuid": "3de081fdf4d54781aae6830f27ddb7e7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3de081fdf4d54781aae6830f27ddb7e7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3de081fdf4d54781aae6830f27ddb7e7"}}, "title": "Balancing selection in Pattern Recognition Receptor signalling pathways is associated with gene function and pleiotropy in a wild rodent.", "authors": [{"family": "Lundberg", "given": "Max", "initials": "M", "orcid": "0000-0002-1895-3622", "researcher": {"href": "https://publications.scilifelab.se/researcher/5b6a6dafa8fe4371ab26ed02ca5a550c.json"}}, {"family": "Zhong", "given": "Xiuqin", "initials": "X", "orcid": "0000-0002-4772-4255", "researcher": {"href": "https://publications.scilifelab.se/researcher/a1847f16fd2a4d1cac925c7b89b70684.json"}}, {"family": "Konrad", "given": "Anna", "initials": "A"}, {"family": "Olsen", "given": "Remi-Andr\u00e9", "initials": "RA"}, {"family": "R\u00e5berg", "given": "Lars", "initials": "L", "orcid": "0000-0001-5219-7448", "researcher": {"href": "https://publications.scilifelab.se/researcher/a732076e5acc4ede94cc864cd90c99f3.json"}}], "type": "journal article", "published": "2020-06-00", "journal": {"volume": "29", "issn": "1365-294X", "issue": "11", "pages": "1990-2003", "title": "Mol. Ecol.", "issn-l": "0962-1083"}, "abstract": "Pathogen-mediated balancing selection is commonly considered to play an important role in the maintenance of genetic diversity, in particular in immune genes. However, the factors that may influence which immune genes are the targets of such selection are largely unknown. To address this, here we focus on Pattern Recognition Receptor (PRR) signalling pathways, which play a key role in innate immunity. We used whole-genome resequencing data from a population of bank voles (Myodes glareolus) to test for associations between balancing selection, pleiotropy and gene function in a set of 123 PRR signalling pathway genes. To investigate the effect of gene function, we compared genes encoding (a) receptors for microbial ligands versus downstream signalling proteins, and (b) receptors recognizing components of microbial cell walls, flagella and capsids versus receptors recognizing features of microbial nucleic acids. Analyses based on the nucleotide diversity of full coding sequences showed that balancing selection primarily targeted receptor genes with a low degree of pleiotropy. Moreover, genes encoding receptors recognizing components of microbial cell walls etc. were more important targets of balancing selection than receptors recognizing nucleic acids. Tests for localized signatures of balancing selection in coding and noncoding sequences showed that such signatures were mostly located in introns, and more evenly distributed among different functional categories of PRR pathway genes. The finding that signatures of balancing selection in full coding sequences primarily occur in receptor genes, in particular those encoding receptors for components of microbial cell walls etc., is consistent with the idea that coevolution between hosts and pathogens is an important cause of balancing selection on immune genes.", "doi": "10.1111/mec.15459", "pmid": "32374503", "labels": {"National Genomics Infrastructure": "Collaborative", "NGI Stockholm (Genomics Applications)": "Collaborative", "NGI Stockholm (Genomics Production)": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "Dryad", "key": "10.5061/dryad.2bvq83bms"}], "notes": [], "created": "2020-07-08T13:04:58.447Z", "modified": "2024-01-16T13:48:42.452Z"}, {"entity": "publication", "iuid": "ee7cd1df9c4e48c086c61222e6510c86", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ee7cd1df9c4e48c086c61222e6510c86.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ee7cd1df9c4e48c086c61222e6510c86"}}, "title": "An immune gene expression signature distinguishes central nervous system metastases from primary tumours in non-small-cell lung cancer.", "authors": [{"family": "Tsakonas", "given": "Georgios", "initials": "G"}, {"family": "Lewensohn", "given": "Rolf", "initials": "R"}, {"family": "Botling", "given": "Johan", "initials": "J"}, {"family": "Ortiz-Villalon", "given": "Cristian", "initials": "C"}, {"family": "Micke", "given": "Patrick", "initials": "P"}, {"family": "Friesland", "given": "Signe", "initials": "S"}, {"family": "Nord", "given": "Helena", "initials": "H"}, {"family": "Lindskog", "given": "Magnus", "initials": "M"}, {"family": "Sandelin", "given": "Martin", "initials": "M"}, {"family": "Hydbring", "given": "Per", "initials": "P"}, {"family": "Ekman", "given": "Simon", "initials": "S", "orcid": "0000-0002-8343-6226", "researcher": {"href": "https://publications.scilifelab.se/researcher/0fcb2b2956a84f43a7b485573f445ff2.json"}}], "type": "journal article", "published": "2020-06-00", "journal": {"title": "Eur. J. Cancer", "issn": "1879-0852", "volume": "132", "issue": null, "pages": "24-34", "issn-l": "0959-8049"}, "abstract": "Dissemination of non-small-cell lung cancer (NSCLC) in the central nervous system is a frequent and challenging clinical problem. Systemic or local therapies rarely prolong survival and have modest activity regarding local control. Alterations in gene expression in brain metastasis versus primary tumour may increase aggressiveness and impair therapeutic efforts.\n\nWe identified 25 patients with surgically removed NSCLC brain metastases in two different patient cohorts. For 13 of these patients, primary tumour samples were available. Gene expression analysis using the nCounter\u00ae PanCancer Immune Profiling gene expression panel (nanoString technologies Inc.) was performed in brain metastases and primary tumour samples. Identification of differentially expressed genes was conducted on normalized data using the nSolver analysis software.\n\nWe compared gene expression patterns in brain metastases with primary tumours. Brain metastasis samples displayed a distinct clustering pattern compared to primary tumour samples with a statistically significant downregulation of genes related to immune response and immune cell activation. Results from KEGG term analysis on differentially expressed genes revealed a concomitant enrichment of multiple KEGG terms associated with the immune system. We identified a 12-gene immune signature that clearly separated brain metastases from primary tumours.\n\nWe identified a unique gene downregulation pattern in brain metastases compared with primary tumours. This finding may explain the lower intracranial efficacy of systemic therapy, especially immunotherapy, in brain metastasis of patients with NSCLC.", "doi": "10.1016/j.ejca.2020.03.014", "pmid": "32325417", "labels": {"Clinical Genomics Uppsala": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0959-8049(20)30155-6"}], "notes": [], "created": "2020-12-08T15:43:55.833Z", "modified": "2024-01-16T13:48:42.459Z"}, {"entity": "publication", "iuid": "a701a9709be141609a88a6452a664266", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a701a9709be141609a88a6452a664266.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a701a9709be141609a88a6452a664266"}}, "title": "Age-of-onset information helps identify 76 genetic variants associated with allergic disease.", "authors": [{"family": "Ferreira", "given": "Manuel A R", "initials": "MAR", "orcid": "0000-0001-9059-1825", "researcher": {"href": "https://publications.scilifelab.se/researcher/d27aef5015494b018b22352125c0225d.json"}}, {"family": "Vonk", "given": "Judith M", "initials": "JM", "orcid": "0000-0001-7531-4547", "researcher": {"href": "https://publications.scilifelab.se/researcher/e57100a0e5bc48c59590c043897a8bbd.json"}}, {"family": "Baurecht", "given": "Hansj\u00f6rg", "initials": "H", "orcid": "0000-0002-9265-5594", "researcher": {"href": "https://publications.scilifelab.se/researcher/65098dade92d4b87a691906582cc4fa9.json"}}, {"family": "Marenholz", "given": "Ingo", "initials": "I"}, {"family": "Tian", "given": "Chao", "initials": "C", "orcid": "0000-0001-7605-7175", "researcher": {"href": "https://publications.scilifelab.se/researcher/7dedf8f815b44a198f28485af5e69846.json"}}, {"family": "Hoffman", "given": "Joshua D", "initials": "JD", "orcid": "0000-0003-2823-1866", "researcher": {"href": "https://publications.scilifelab.se/researcher/a9f5e78834914d7699717e488827d616.json"}}, {"family": "Helmer", "given": "Quinta", "initials": "Q"}, {"family": "Tillander", "given": "Annika", "initials": "A", "orcid": "0000-0002-9239-9471", "researcher": {"href": "https://publications.scilifelab.se/researcher/b495409505824c8794717fd9b507a1f7.json"}}, {"family": "Ullemar", "given": "Vilhelmina", "initials": "V", "orcid": "0000-0002-8759-765X", "researcher": {"href": "https://publications.scilifelab.se/researcher/bf34fc1ddb7644edbabe552010e8754f.json"}}, {"family": "Lu", "given": "Yi", "initials": "Y", "orcid": "0000-0001-9933-3654", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a73eafe0b0e4221a77b96800883413d.json"}}, {"family": "Grosche", "given": "Sarah", "initials": "S"}, {"family": "R\u00fcschendorf", "given": "Franz", "initials": "F"}, {"family": "Granell", "given": "Raquel", "initials": "R", "orcid": "0000-0002-4890-4012", "researcher": {"href": "https://publications.scilifelab.se/researcher/44c4fdcdcf6149ba8b48366f9ba707d9.json"}}, {"family": "Brumpton", "given": "Ben M", "initials": "BM", "orcid": "0000-0002-3058-1059", "researcher": {"href": "https://publications.scilifelab.se/researcher/da9d23aaf1dc4d18a0a13e4847ea9955.json"}}, {"family": "Fritsche", "given": "Lars G", "initials": "LG", "orcid": "0000-0002-2110-1690", "researcher": {"href": "https://publications.scilifelab.se/researcher/00bea312a34a4b8f8436d00fcf799ac3.json"}}, {"family": "Bhatta", "given": "Laxmi", "initials": "L", "orcid": "0000-0002-8166-1470", "researcher": {"href": "https://publications.scilifelab.se/researcher/7833d21a70224f6da9d1b10982bb567f.json"}}, {"family": "Gabrielsen", "given": "Maiken E", "initials": "ME"}, {"family": "Nielsen", "given": "Jonas B", "initials": "JB"}, {"family": "Zhou", "given": "Wei", "initials": "W", "orcid": "0000-0001-7719-0859", "researcher": {"href": "https://publications.scilifelab.se/researcher/78c70f5da0ef414680693f1c41dcf99a.json"}}, {"family": "Hveem", "given": "Kristian", "initials": "K"}, {"family": "Langhammer", "given": "Arnulf", "initials": "A", "orcid": "0000-0001-5296-6673", "researcher": {"href": "https://publications.scilifelab.se/researcher/755b4b39d8054f2ea3e28476a7b0ae39.json"}}, {"family": "Holmen", "given": "Oddgeir L", "initials": "OL"}, {"family": "L\u00f8set", "given": "Mari", "initials": "M"}, {"family": "Abecasis", "given": "Gon\u00e7alo R", "initials": "GR"}, {"family": "Willer", "given": "Cristen J", "initials": "CJ"}, {"family": "Emami", "given": "Nima C", "initials": "NC", "orcid": "0000-0002-4296-7805", "researcher": {"href": "https://publications.scilifelab.se/researcher/4fc068c6fb6a4ca7a8e7434cb2a4b4f2.json"}}, {"family": "Cavazos", "given": "Taylor B", "initials": "TB", "orcid": "0000-0003-3537-2608", "researcher": {"href": "https://publications.scilifelab.se/researcher/9c03835393864b859639733cb2e64e09.json"}}, {"family": "Witte", "given": "John S", "initials": "JS"}, {"family": "Szwajda", "given": "Agnieszka", "initials": "A", "orcid": "0000-0003-2073-6018", "researcher": {"href": "https://publications.scilifelab.se/researcher/72343d922a0648598d53a02da82a68c8.json"}}, {"family": "23andMe Research Team", "given": "", "initials": ""}, {"family": "collaborators of the SHARE study", "given": "", "initials": ""}, {"family": "Hinds", "given": "David A", "initials": "DA", "orcid": "0000-0002-4911-803X", "researcher": {"href": "https://publications.scilifelab.se/researcher/ba56969917d14df0bd923a54ce9f911d.json"}}, {"family": "H\u00fcbner", "given": "Norbert", "initials": "N"}, {"family": "Weidinger", "given": "Stephan", "initials": "S"}, {"family": "Magnusson", "given": "Patrik Ke", "initials": "PK", "orcid": "0000-0002-7315-7899", "researcher": {"href": "https://publications.scilifelab.se/researcher/b277b6387de142bbab91fad82d9eff09.json"}}, {"family": "Jorgenson", "given": "Eric", "initials": "E", "orcid": "0000-0002-5829-8191", "researcher": {"href": "https://publications.scilifelab.se/researcher/38ef095c3de94bbc884d80c8949d16f5.json"}}, {"family": "Karlsson", "given": "Robert", "initials": "R", "orcid": "0000-0002-8949-2587", "researcher": {"href": "https://publications.scilifelab.se/researcher/9df14bf33f3342408d624caa70d45b7c.json"}}, {"family": "Paternoster", "given": "Lavinia", "initials": "L", "orcid": "0000-0003-2514-0889", "researcher": {"href": "https://publications.scilifelab.se/researcher/826f9852c56d4922ab255ab83d26faa8.json"}}, {"family": "Boomsma", "given": "Dorret I", "initials": "DI", "orcid": "0000-0002-7099-7972", "researcher": {"href": "https://publications.scilifelab.se/researcher/4b66ab2525fd4a468e7a4ad14c955cb4.json"}}, {"family": "Almqvist", "given": "Catarina", "initials": "C", "orcid": "0000-0002-1045-1898", "researcher": {"href": "https://publications.scilifelab.se/researcher/c7b0899897f046499272a916fd0c6ba5.json"}}, {"family": "Lee", "given": "Young-Ae", "initials": "Y"}, {"family": "Koppelman", "given": "Gerard H", "initials": "GH", "orcid": "0000-0001-8567-3252", "researcher": {"href": "https://publications.scilifelab.se/researcher/cd7e0158050a4ab3860e288c4eb9ae87.json"}}], "type": "journal article", "published": "2020-06-00", "journal": {"title": "PLoS Genet.", "issn": "1553-7404", "issn-l": "1553-7390", "volume": "16", "issue": "6", "pages": "e1008725"}, "abstract": "Risk factors that contribute to inter-individual differences in the age-of-onset of allergic diseases are poorly understood. The aim of this study was to identify genetic risk variants associated with the age at which symptoms of allergic disease first develop, considering information from asthma, hay fever and eczema. Self-reported age-of-onset information was available for 117,130 genotyped individuals of European ancestry from the UK Biobank study. For each individual, we identified the earliest age at which asthma, hay fever and/or eczema was first diagnosed and performed a genome-wide association study (GWAS) of this combined age-of-onset phenotype. We identified 50 variants with a significant independent association (P<3x10-8) with age-of-onset. Forty-five variants had comparable effects on the onset of the three individual diseases and 38 were also associated with allergic disease case-control status in an independent study (n = 222,484). We observed a strong negative genetic correlation between age-of-onset and case-control status of allergic disease (rg = -0.63, P = 4.5x10-61), indicating that cases with early disease onset have a greater burden of allergy risk alleles than those with late disease onset. Subsequently, a multivariate GWAS of age-of-onset and case-control status identified a further 26 associations that were missed by the univariate analyses of age-of-onset or case-control status only. Collectively, of the 76 variants identified, 18 represent novel associations for allergic disease. We identified 81 likely target genes of the 76 associated variants based on information from expression quantitative trait loci (eQTL) and non-synonymous variants, of which we highlight ADAM15, FOSL2, TRIM8, BMPR2, CD200R1, PRKCQ, NOD2, SMAD4, ABCA7 and UBE2L3. Our results support the notion that early and late onset allergic disease have partly distinct genetic architectures, potentially explaining known differences in pathophysiology between individuals.", "doi": "10.1371/journal.pgen.1008725", "pmid": "32603359", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pii", "key": "PGENETICS-D-18-02006"}, {"db": "pmc", "key": "PMC7367489"}], "notes": [], "created": "2021-01-07T17:01:52.734Z", "modified": "2021-12-07T13:51:25.031Z"}, {"entity": "publication", "iuid": "e78f5c80e0f7468e9c635acda6db895d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e78f5c80e0f7468e9c635acda6db895d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e78f5c80e0f7468e9c635acda6db895d"}}, "title": "Activated carbon stimulates microbial diversity and PAH biodegradation under anaerobic conditions in oil-polluted sediments.", "authors": [{"family": "Bonaglia", "given": "Stefano", "initials": "S", "orcid": "0000-0003-4366-0677", "researcher": {"href": "https://publications.scilifelab.se/researcher/c02dd99f9fd14dd89d5c231260806720.json"}}, {"family": "Broman", "given": "Elias", "initials": "E", "orcid": "0000-0001-9005-5168", "researcher": {"href": "https://publications.scilifelab.se/researcher/63826da04a1f4f80bc3229df12bac9b7.json"}}, {"family": "Brindefalk", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Hedlund", "given": "Erika", "initials": "E"}, {"family": "Hjorth", "given": "Tomas", "initials": "T"}, {"family": "Rolff", "given": "Carl", "initials": "C"}, {"family": "Nascimento", "given": "Francisco J A", "initials": "FJA"}, {"family": "Udekwu", "given": "Klas", "initials": "K"}, {"family": "Gunnarsson", "given": "Jonas S", "initials": "JS"}], "type": "journal article", "published": "2020-06-00", "journal": {"title": "Chemosphere", "issn": "1879-1298", "volume": "248", "issue": null, "pages": "126023", "issn-l": "0045-6535"}, "abstract": "Biodegradation by microorganisms is a useful tool that helps alleviating hydrocarbon pollution in nature. Microbes are more efficient in degradation under aerobic than anaerobic conditions, but the majority of sediment by volume is generally anoxic. Incubation experiments were conducted to study the biodegradation potential of naphthalene-a common polycyclic aromatic hydrocarbon (PAH)-and the diversity of microbial communities in presence/absence of activated carbon (AC) under aerobic/anaerobic conditions. Radio-respirometry experiments with endogenous microorganisms indicated that degradation of naphthalene was strongly stimulated (96%) by the AC addition under anaerobic conditions. In aerobic conditions, however, AC had no effects on naphthalene biodegradation. Bioaugmentation tests with cultured microbial populations grown on naphthalene showed that AC further stimulated (92%) naphthalene degradation in anoxia. Analysis of the 16S rRNA gene sequences implied that sediment amendment with AC increased microbial community diversity and changed community structure. Moreover, the relative abundance of Geobacter, Thiobacillus, Sulfuricurvum, and methanogenic archaea increased sharply after amendment with AC under anaerobic conditions. These results may be explained by the fact that AC particles promoted direct interspecies electron transfer (DIET) between microorganisms involved in PAH degradation pathways. We suggest that important ecosystem functions mediated by microbes-such as hydrocarbon degradation-can be induced and that AC enrichment strategies can be exploited for facilitating bioremediation of anoxic oil-contaminated sediments and soils.", "doi": "10.1016/j.chemosphere.2020.126023", "pmid": "32007777", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S0045-6535(20)30216-2"}], "notes": [], "created": "2020-07-08T13:03:41.428Z", "modified": "2024-01-16T13:48:42.467Z"}, {"entity": "publication", "iuid": "7c8b4a4859ad48729c578fc278db0e40", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7c8b4a4859ad48729c578fc278db0e40.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7c8b4a4859ad48729c578fc278db0e40"}}, "title": "Restoration of KMT2C/MLL3 in human colorectal cancer cells reinforces genome-wide H3K4me1 profiles and influences cell growth and gene expression.", "authors": [{"family": "Larsson", "given": "Chatarina", "initials": "C"}, {"family": "Cordeddu", "given": "Lina", "initials": "L"}, {"family": "Siggens", "given": "Lee", "initials": "L"}, {"family": "Pandzic", "given": "Tatjana", "initials": "T"}, {"family": "Kundu", "given": "Snehangshu", "initials": "S"}, {"family": "He", "given": "Liqun", "initials": "L"}, {"family": "Ali", "given": "Muhammad Akhtar", "initials": "MA"}, {"family": "Pristov\u0161ek", "given": "Nu\u0161a", "initials": "N"}, {"family": "Hartman", "given": "Karin", "initials": "K"}, {"family": "Ekwall", "given": "Karl", "initials": "K"}, {"family": "Sj\u00f6blom", "given": "Tobias", "initials": "T", "orcid": "0000-0001-6668-4140", "researcher": {"href": "https://publications.scilifelab.se/researcher/909f00a5bf6e465f9ff560b12bcd863a.json"}}], "type": "journal article", "published": "2020-05-29", "journal": {"title": "Clin Epigenetics", "issn": "1868-7083", "volume": "12", "issue": "1", "pages": "74", "issn-l": "1868-7075"}, "abstract": "The histone 3 lysine 4 (H3K4) monomethylase KMT2C is mutated across several cancer types; however, the effects of mutations on epigenome organization, gene expression, and cell growth are not clear. A frequently recurring mutation in colorectal cancer (CRC) with microsatellite instability is a single nucleotide deletion within the exon 38 poly-A(9) repeat (c.8390delA) which results in frameshift preceding the functional carboxy-terminal SET domain. To study effects of KMT2C expression in CRC cells, we restored one allele to wild type KMT2C in the two CRC cell lines RKO and HCT116, which both are homozygous c.8390delA mutant.\n\nGene editing resulted in increased KMT2C expression, increased H3K4me1 levels, altered gene expression profiles, and subtle negative effects on cell growth, where higher dependence and stronger effects of KMT2C expression were observed in RKO compared to HCT116 cells. Surprisingly, we found that the two RKO and HCT116 CRC cell lines have distinct baseline H3K4me1 epigenomic profiles. In RKO cells, a flatter genome-wide H3K4me1 profile was associated with more increased H3K4me1 deposition at enhancers, reduced cell growth, and more differential gene expression relative to HCT116 cells when KMT2C was restored. Profiling of H3K4me1 did not indicate a highly specific regulation of gene expression as KMT2C-induced H3K4me1 deposition was found globally and not at a specific enhancer sub-set in the engineered cells. Although we observed variation in differentially regulated gene sets between cell lines and individual clones, differentially expressed genes in both cell lines included genes linked to known cancer signaling pathways, estrogen response, hypoxia response, and aspects of immune system regulation.\n\nHere, KMT2C restoration reduced CRC cell growth and reinforced genome-wide H3K4me1 deposition at enhancers; however, the effects varied depending upon the H3K4me1 status of KMT2C deficient cells. Results indicate that KMT2C inactivation may promote colorectal cancer development through transcriptional dysregulation in several pathways with known cancer relevance.", "doi": "10.1186/s13148-020-00863-z", "pmid": "32471474", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s13148-020-00863-z"}, {"db": "pmc", "key": "PMC7257146"}], "notes": [], "created": "2020-08-25T13:15:07.034Z", "modified": "2024-01-16T13:48:42.473Z"}, {"entity": "publication", "iuid": "412601f6ba354736b3238fd089ebe0cf", "links": {"self": {"href": "https://publications.scilifelab.se/publication/412601f6ba354736b3238fd089ebe0cf.json"}, "display": {"href": "https://publications.scilifelab.se/publication/412601f6ba354736b3238fd089ebe0cf"}}, "title": "In silico Druggability Assessment of the NUDIX Hydrolase Protein Family as a Workflow for Target Prioritization.", "authors": [{"family": "Michel", "given": "Maurice", "initials": "M"}, {"family": "Homan", "given": "Evert J", "initials": "EJ"}, {"family": "Wiita", "given": "Elis\u00e9e", "initials": "E"}, {"family": "Pedersen", "given": "Kia", "initials": "K"}, {"family": "Alml\u00f6f", "given": "Ingrid", "initials": "I"}, {"family": "Gustavsson", "given": "Anna-Lena", "initials": "AL", "orcid": "0000-0003-4332-2336", "researcher": {"href": "https://publications.scilifelab.se/researcher/6b014ef7ea0d461b8e2ddb87506b1252.json"}}, {"family": "Lundb\u00e4ck", "given": "Thomas", "initials": "T"}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}, {"family": "Warpman Berglund", "given": "Ulrika", "initials": "U"}], "type": "journal article", "published": "2020-05-29", "journal": {"volume": "8", "issn": "2296-2646", "issue": null, "pages": "443", "title": "Front. Chem.", "issn-l": "2296-2646"}, "abstract": "Computational chemistry has now been widely accepted as a useful tool for shortening lead times in early drug discovery. When selecting new potential drug targets, it is important to assess the likelihood of finding suitable starting points for lead generation before pursuing costly high-throughput screening campaigns. By exploiting available high-resolution crystal structures, an in silico druggability assessment can facilitate the decision of whether, and in cases where several protein family members exist, which of these to pursue experimentally. Many of the algorithms and software suites commonly applied for in silico druggability assessment are complex, technically challenging and not always user-friendly. Here we applied the intuitive open access servers of DoGSite, FTMap and CryptoSite to comprehensively predict ligand binding pockets, druggability scores and conformationally active regions of the NUDIX protein family. In parallel we analyzed potential ligand binding sites, their druggability and pocket parameter using Schr\u00f6dinger's SiteMap. Then an in silico docking cascade of a subset of the ZINC FragNow library using the Glide docking program was performed to assess identified pockets for large-scale small-molecule binding. Subsequently, this initial dual ranking of druggable sites within the NUDIX protein family was benchmarked against experimental hit rates obtained both in-house and by others from traditional biochemical and fragment screening campaigns. The observed correlation suggests that the presented user-friendly workflow of a dual parallel in silico druggability assessment is applicable as a standalone method for decision on target prioritization and exclusion in future screening campaigns.", "doi": "10.3389/fchem.2020.00443", "pmid": "32548091", "labels": {"Protein Science Facility (PSF)": "Service", "Chemical Biology Consortium Sweden": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC7274155"}], "notes": [], "created": "2020-06-02T11:23:46.275Z", "modified": "2025-10-17T13:04:28.304Z"}, {"entity": "publication", "iuid": "24c1864eab62411f9d39198e02fc37de", "links": {"self": {"href": "https://publications.scilifelab.se/publication/24c1864eab62411f9d39198e02fc37de.json"}, "display": {"href": "https://publications.scilifelab.se/publication/24c1864eab62411f9d39198e02fc37de"}}, "title": "Transitions in wheat endosperm metabolism upon transcriptional induction of oil accumulation by oat endosperm WRINKLED1.", "authors": [{"family": "Grimberg", "given": "\u00c5sa", "initials": "\u00c5", "orcid": "0000-0002-3083-7448", "researcher": {"href": "https://publications.scilifelab.se/researcher/e237918aef734c6b89ffa5f551d6e3a6.json"}}, {"family": "Wilkinson", "given": "Mark", "initials": "M"}, {"family": "Snell", "given": "Per", "initials": "P"}, {"family": "De Vos", "given": "Rebecca P", "initials": "RP"}, {"family": "Gonz\u00e1lez-Thuillier", "given": "Irene", "initials": "I"}, {"family": "Tawfike", "given": "Ahmed", "initials": "A"}, {"family": "Ward", "given": "Jane L", "initials": "JL"}, {"family": "Carlsson", "given": "Anders S", "initials": "AS"}, {"family": "Shewry", "given": "Peter", "initials": "P"}, {"family": "Hofvander", "given": "Per", "initials": "P"}], "type": "journal article", "published": "2020-05-25", "journal": {"title": "BMC Plant Biol.", "issn": "1471-2229", "volume": "20", "issue": "1", "pages": "235", "issn-l": "1471-2229"}, "abstract": "Cereal grains, including wheat (Triticum aestivum L.), are major sources of food and feed, with wheat being dominant in temperate zones. These end uses exploit the storage reserves in the starchy endosperm of the grain, with starch being the major storage component in most cereal species. However, oats (Avena sativa L.) differs in that the starchy endosperm stores significant amounts of oil. Understanding the control of carbon allocation between groups of storage compounds, such as starch and oil, is therefore important for understanding the composition and hence end use quality of cereals. WRINKLED1 is a transcription factor known to induce triacylglycerol (TAG; oil) accumulation in several plant storage tissues.\n\nAn oat endosperm homolog of WRI1 (AsWRI1) expressed from the endosperm-specific HMW1Dx5 promoter resulted in drastic changes in carbon allocation in wheat grains, with reduced seed weight and a wrinkled seed phenotype. The starch content of mature grain endosperms of AsWRI1-wheat was reduced compared to controls (from 62 to 22% by dry weight (dw)), TAG was increased by up to nine-fold (from 0.7 to 6.4% oil by dw) and sucrose from 1.5 to 10% by dw. Expression of AsWRI1 in wheat grains also resulted in multiple layers of elongated peripheral aleurone cells. RNA-sequencing, lipid analyses, and pulse-chase experiments using 14C-sucrose indicated that futile cycling of fatty acids could be a limitation for oil accumulation.\n\nOur data show that expression of oat endosperm WRI1 in the wheat endosperm results in changes in metabolism which could underpin the application of biotechnology to manipulate grain composition. In particular, the striking effect on starch synthesis in the wheat endosperm indicates that an important indirect role of WRI1 is to divert carbon allocation away from starch biosynthesis in plant storage tissues that accumulate oil.", "doi": "10.1186/s12870-020-02438-9", "pmid": "32450804", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12870-020-02438-9"}, {"db": "pmc", "key": "PMC7249431"}], "notes": [], "created": "2020-07-03T05:28:46.118Z", "modified": "2021-11-10T12:50:50.964Z"}, {"entity": "publication", "iuid": "9f90d87b1407413a83ea24c025ed5e80", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9f90d87b1407413a83ea24c025ed5e80.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9f90d87b1407413a83ea24c025ed5e80"}}, "title": "Staphylococcus argenteus as an etiological agent of prosthetic hip joint infection: a case presentation.", "authors": [{"family": "S\u00f6derquist", "given": "Bo", "initials": "B"}, {"family": "Wildeman", "given": "Peter", "initials": "P"}, {"family": "Stenmark", "given": "Bianca", "initials": "B", "orcid": "0000-0003-4637-8626", "researcher": {"href": "https://publications.scilifelab.se/researcher/726c71c7aca148c981b48bde574a2e1c.json"}}, {"family": "Stegger", "given": "Marc", "initials": "M"}], "type": "journal article", "published": "2020-05-25", "journal": {"title": "J Bone Jt Infect", "issn": "2206-3552", "issn-l": null, "volume": "5", "issue": "4", "pages": "172-175"}, "abstract": "This report presents a case of prosthetic hip infection caused by Staphylococcus argenteus, a potentially overlooked etiology of prosthetic joint infections (PJIs). Whole-genome sequencing showed that the S. argenteus isolate was an ST2250 and clustered within other CC2250 isolates, the largest clonal group of S. argenteus. This sequence type is prevalent and may be associated with invasive infections. The present isolate was phenotypically fully susceptible to all tested antimicrobial agents and genome analysis did not detect any resistance genes, nor were any staphylococcal cassette chromosome residues detected. Despite initial appropriate management with debridement and biofilm-active antibiotics, the outcome was unfavorable with recurrence and a persistent infection treated with suppressive antibiotics. Regarding the repertoire of genomic traits for virulence in S. argenteus, PJIs caused by this bacterium should be treated accordingly as Staphylococcus aureus PJIs.", "doi": "10.7150/jbji.44848", "pmid": "32670770", "labels": {"Clinical Genomics \u00d6rebro": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "jbjiv05p0172"}, {"db": "pmc", "key": "PMC7358968"}], "notes": [], "created": "2020-11-27T13:57:12.857Z", "modified": "2021-12-08T12:31:15.365Z"}, {"entity": "publication", "iuid": "c2cb0bab4db649efac151742b39cf0bb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c2cb0bab4db649efac151742b39cf0bb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c2cb0bab4db649efac151742b39cf0bb"}}, "title": "Auxin export from proximal fruits drives arrest in temporally competent inflorescences", "authors": [{"family": "Ware", "given": "Alexander", "initials": "A"}, {"family": "Walker", "given": "Catriona H", "initials": "CH", "orcid": "0000-0001-7854-4348", "researcher": {"href": "https://publications.scilifelab.se/researcher/37ada8225d8e4931b1d093af5a71306e.json"}}, {"family": "\u0160imura", "given": "Jan", "initials": "J"}, {"family": "Gonz\u00e1lez-Su\u00e1rez", "given": "Pablo", "initials": "P", "orcid": "0000-0002-2122-5984", "researcher": {"href": "https://publications.scilifelab.se/researcher/770ac95b3e6c44e28967de3fb8fbe149.json"}}, {"family": "Ljung", "given": "Karin", "initials": "K", "orcid": "0000-0003-2901-189X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f91b1e1f90c24559b915ebcd265804a4.json"}}, {"family": "Bishopp", "given": "Anthony", "initials": "A"}, {"family": "Wilson", "given": "Zoe A", "initials": "ZA", "orcid": "0000-0003-0948-8770", "researcher": {"href": "https://publications.scilifelab.se/researcher/76cb7bfa2b1c4961ad52a2080f7c9822.json"}}, {"family": "Bennett", "given": "Tom", "initials": "T", "orcid": "0000-0003-1612-4019", "researcher": {"href": "https://publications.scilifelab.se/researcher/f39f318b0f094229aa34d1c137575d6b.json"}}], "type": "journal-article", "published": "2020-05-25", "journal": {"title": "NPLANTS", "issn": "2055-0278", "issn-l": "2055-0278", "volume": "6", "issue": "6", "pages": "699-707"}, "abstract": "A well-defined set of regulatory pathways control entry into the reproductive phase in flowering plants, but little is known about the mechanistic control of the end-of-flowering despite this being a critical process for optimization of fruit and seed production. Complete fruit removal, or lack of fertile fruit-set, prevents timely inflorescence arrest in Arabidopsis, leading to a previous proposal that a cumulative fruit/seed-derived signal causes simultaneous 'global proliferative arrest'. Recent studies have suggested that inflorescence arrest involves gene expression changes in the inflorescence meristem that are, at least in part, controlled by the FRUITFULL-APETALA2 pathway; however, there is limited understanding of how this process is coordinated at the whole-plant level. Here, we provide a framework for the communication previously inferred in the global proliferative arrest model. We show that the end-of-flowering in Arabidopsis is not 'global' and does not occur synchronously between branches, but rather that the arrest of each inflorescence is a local process, driven by auxin export from fruit proximal to the inflorescence apex. Furthermore, we show that inflorescences are competent for arrest only once they reach a certain developmental age. Understanding the regulation of inflorescence arrest will be of major importance to extending and maximizing crop yields.", "doi": "10.1038/s41477-020-0661-z", "pmid": "32451444", "labels": {"Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41477-020-0661-z"}], "notes": [], "created": "2020-01-21T10:14:13.466Z", "modified": "2025-10-17T13:03:16.780Z"}, {"entity": "publication", "iuid": "d98c58bf1e6e4de9b468b52b6592fa41", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d98c58bf1e6e4de9b468b52b6592fa41.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d98c58bf1e6e4de9b468b52b6592fa41"}}, "title": "Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction.", "authors": [{"family": "Ntalla", "given": "Ioanna", "initials": "I"}, {"family": "Weng", "given": "Lu-Chen", "initials": "LC", "orcid": "0000-0003-1475-4930", "researcher": {"href": 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"given": "Michele", "initials": "M", "orcid": "0000-0001-5773-0344", "researcher": {"href": "https://publications.scilifelab.se/researcher/ad2b6285769e43d59eaa61068cd9307d.json"}}, {"family": "Ramirez", "given": "Julia", "initials": "J", "orcid": "0000-0003-4130-5866", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff795d161ab5418ebbb32c64fc9628cf.json"}}, {"family": "Van Duijvenboden", "given": "Stefan", "initials": "S", "orcid": "0000-0001-8897-558X", "researcher": {"href": "https://publications.scilifelab.se/researcher/bedcb22e237147019c8a97c32e164456.json"}}, {"family": "Arnar", "given": "David O", "initials": "DO"}, {"family": "Gudbjartsson", "given": "Daniel F", "initials": "DF", "orcid": "0000-0002-5222-9857", "researcher": {"href": "https://publications.scilifelab.se/researcher/e41ffdc303534408aade6e4a071e4801.json"}}, {"family": "Holm", "given": "Hilma", "initials": "H"}, {"family": "Sulem", "given": "Patrick", "initials": "P", "orcid": "0000-0001-7123-6123", "researcher": {"href": "https://publications.scilifelab.se/researcher/a228963aa2c148ee82e526d07e298364.json"}}, {"family": "Thorleifsson", "given": "Gudmar", "initials": "G"}, {"family": "Thorolfsdottir", "given": "Rosa B", "initials": "RB", "orcid": "0000-0001-7475-0398", "researcher": {"href": "https://publications.scilifelab.se/researcher/e803af5742504636a2d16ae252f94af4.json"}}, {"family": "Thorsteinsdottir", "given": "Unnur", "initials": "U"}, {"family": "Benjamin", "given": "Emelia J", "initials": "EJ", "orcid": "0000-0003-4076-2336", "researcher": {"href": "https://publications.scilifelab.se/researcher/31c69bdf118d4b36ad65a6c4f780bab2.json"}}, {"family": "Tinker", "given": "Andrew", "initials": "A"}, {"family": "Stefansson", "given": "Kari", "initials": "K", "orcid": "0000-0003-1676-864X", "researcher": {"href": "https://publications.scilifelab.se/researcher/679465193fba4887a68e2aec34ccfd8e.json"}}, {"family": "Ellinor", "given": "Patrick T", "initials": "PT", "orcid": "0000-0002-2067-0533", "researcher": {"href": "https://publications.scilifelab.se/researcher/dd513dc49e0945bc8298f72d1244648d.json"}}, {"family": "Jamshidi", "given": "Yalda", "initials": "Y", "orcid": "0000-0003-0151-6482", "researcher": {"href": "https://publications.scilifelab.se/researcher/66a90ee88cbf4e9b9e782548fe4991c0.json"}}, {"family": "Lubitz", "given": "Steven A", "initials": "SA", "orcid": "0000-0002-9599-4866", "researcher": {"href": "https://publications.scilifelab.se/researcher/25bb007311104c92983dbcce80f72260.json"}}, {"family": "Munroe", "given": "Patricia B", "initials": "PB", "orcid": "0000-0002-4176-2947", "researcher": {"href": "https://publications.scilifelab.se/researcher/657544a7f921459f926aae5cd0e2065c.json"}}], "type": "journal article", "published": "2020-05-21", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "11", "issue": "1", "pages": "2542", "issn-l": "2041-1723"}, "abstract": "The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N = 293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease.", "doi": "10.1038/s41467-020-15706-x", "pmid": "32439900", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-15706-x"}, {"db": "pmc", "key": "PMC7242331"}], "notes": [], "created": "2020-05-27T13:29:26.954Z", "modified": "2021-11-10T12:50:53.503Z"}, {"entity": "publication", "iuid": "c0f9c1e3aaba4bf78198e30390d7a5cb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c0f9c1e3aaba4bf78198e30390d7a5cb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c0f9c1e3aaba4bf78198e30390d7a5cb"}}, "title": "Integration of whole-body [18F]FDG PET/MRI with non-targeted metabolomics can provide new insights on tissue-specific insulin resistance in type 2 diabetes.", "authors": [{"family": "Diamanti", "given": "Klev", "initials": "K"}, {"family": "Visvanathar", "given": "Robin", "initials": "R"}, {"family": "Pereira", "given": "Maria J", "initials": "MJ"}, {"family": "Cavalli", "given": "Marco", "initials": "M"}, {"family": "Pan", "given": "Gang", "initials": "G"}, {"family": "Kumar", "given": "Chanchal", "initials": "C"}, {"family": "Skrtic", "given": "Stanko", "initials": "S"}, {"family": "Ris\u00e9rus", "given": "Ulf", "initials": "U"}, {"family": "Eriksson", "given": "Jan W", "initials": "JW"}, {"family": "Kullberg", "given": "Joel", "initials": "J"}, {"family": "Komorowski", "given": "Jan", "initials": "J"}, {"family": "Wadelius", "given": "Claes", "initials": "C"}, {"family": "Ahlstr\u00f6m", "given": "H\u00e5kan", "initials": "H"}], "type": "journal article", "published": "2020-05-20", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "8343", "issn-l": "2045-2322"}, "abstract": "Alteration of various metabolites has been linked to type 2 diabetes (T2D) and insulin resistance. However, identifying significant associations between metabolites and tissue-specific phenotypes requires a multi-omics approach. In a cohort of 42 subjects with different levels of glucose tolerance (normal, prediabetes and T2D) matched for age and body mass index, we calculated associations between parameters of whole-body positron emission tomography (PET)/magnetic resonance imaging (MRI) during hyperinsulinemic euglycemic clamp and non-targeted metabolomics profiling for subcutaneous adipose tissue (SAT) and plasma. Plasma metabolomics profiling revealed that hepatic fat content was positively associated with tyrosine, and negatively associated with lysoPC(P-16:0). Visceral adipose tissue (VAT) and SAT insulin sensitivity (Ki), were positively associated with several lysophospholipids, while the opposite applied to branched-chain amino acids. The adipose tissue metabolomics revealed a positive association between non-esterified fatty acids and, VAT and liver Ki. Bile acids and carnitines in adipose tissue were inversely associated with VAT Ki. Furthermore, we detected several metabolites that were significantly higher in T2D than normal/prediabetes. In this study we present novel associations between several metabolites from SAT and plasma with the fat fraction, volume and insulin sensitivity of various tissues throughout the body, demonstrating the benefit of an integrative multi-omics approach.", "doi": "10.1038/s41598-020-64524-0", "pmid": "32433479", "labels": {"Bioinformatics Support for Computational Resources": "Service", "Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-64524-0"}, {"db": "pmc", "key": "PMC7239946"}], "notes": [], "created": "2020-12-11T11:56:10.100Z", "modified": "2025-10-17T13:03:16.813Z"}, {"entity": "publication", "iuid": "1931acc06b2149ed84e7bb277ac30b26", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1931acc06b2149ed84e7bb277ac30b26.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1931acc06b2149ed84e7bb277ac30b26"}}, "title": "Comprehensive metabolomics analysis of prostate cancer tissue in relation to tumor aggressiveness and TMPRSS2-ERG fusion status.", "authors": [{"family": "Dudka", "given": "Ilona", "initials": "I"}, {"family": "Thysell", "given": "Elin", "initials": "E"}, {"family": "Lundquist", "given": "Kristina", "initials": "K"}, {"family": "Antti", "given": "Henrik", "initials": "H"}, {"family": "Iglesias-Gato", "given": "Diego", "initials": "D"}, {"family": "Flores-Morales", "given": "Amilcar", "initials": "A"}, {"family": "Bergh", "given": "Anders", "initials": "A"}, {"family": "Wikstr\u00f6m", "given": "Pernilla", "initials": "P"}, {"family": "Gr\u00f6bner", "given": "Gerhard", "initials": "G", "orcid": "0000-0001-7380-8797", "researcher": {"href": "https://publications.scilifelab.se/researcher/85bd86ebc85d4653bc880bc9be25bc80.json"}}], "type": "journal article", "published": "2020-05-18", "journal": {"title": "BMC Cancer", "issn": "1471-2407", "volume": "20", "issue": "1", "pages": "437", "issn-l": "1471-2407"}, "abstract": "Prostate cancer (PC) can display very heterogeneous phenotypes ranging from indolent asymptomatic to aggressive lethal forms. Understanding how these PC subtypes vary in their striving for energy and anabolic molecules is of fundamental importance for developing more effective therapies and diagnostics. Here, we carried out an extensive analysis of prostate tissue samples to reveal metabolic alterations during PC development and disease progression and furthermore between TMPRSS2-ERG rearrangement-positive and -negative PC subclasses.\n\nComprehensive metabolomics analysis of prostate tissue samples was performed by non-destructive high-resolution magic angle spinning nuclear magnetic resonance (1H HR MAS NMR). Subsequently, samples underwent moderate extraction, leaving tissue morphology intact for histopathological characterization. Metabolites in tissue extracts were identified by 1H/31P NMR and liquid chromatography-mass spectrometry (LC-MS). These metabolomics profiles were analyzed by chemometric tools and the outcome was further validated using proteomic data from a separate sample cohort.\n\nThe obtained metabolite patterns significantly differed between PC and benign tissue and between samples with high and low Gleason score (GS). Five key metabolites (phosphocholine, glutamate, hypoxanthine, arginine and \u03b1-glucose) were identified, who were sufficient to differentiate between cancer and benign tissue and between high to low GS. In ERG-positive PC, the analysis revealed several acylcarnitines among the increased metabolites together with decreased levels of proteins involved in \u03b2-oxidation; indicating decreased acyl-CoAs oxidation in ERG-positive tumors. The ERG-positive group also showed increased levels of metabolites and proteins involved in purine catabolism; a potential sign of increased DNA damage and oxidative stress.\n\nOur comprehensive metabolomic analysis strongly indicates that ERG-positive PC and ERG-negative PC should be considered as different subtypes of PC; a fact requiring different, sub-type specific treatment strategies for affected patients.", "doi": "10.1186/s12885-020-06908-z", "pmid": "32423389", "labels": {"Swedish Metabolomics Centre": "Service", "Swedish NMR Centre": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1186/s12885-020-06908-z"}, {"db": "pmc", "key": "PMC7236196"}], "notes": [], "created": "2020-11-24T20:28:48.037Z", "modified": "2025-10-17T13:03:56.902Z"}, {"entity": "publication", "iuid": "d3e578769e7c46bd9ce5916ae0107107", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d3e578769e7c46bd9ce5916ae0107107.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d3e578769e7c46bd9ce5916ae0107107"}}, "title": "Behavioral Characterization of dmrt3a Mutant Zebrafish Reveals Crucial Aspects of Vertebrate Locomotion through Phenotypes Related to Acceleration.", "authors": [{"family": "Del Pozo", "given": "Ana", "initials": "A"}, {"family": "Manuel", "given": "Remy", "initials": "R"}, {"family": "Iglesias Gonzalez", "given": "Ana Belen", "initials": "AB"}, {"family": "Koning", "given": "Harmen Kornelis", "initials": "HK"}, {"family": "Habicher", "given": "Judith", "initials": "J"}, {"family": "Zhang", "given": "Hanqing", "initials": "H"}, {"family": "Allalou", "given": "Amin", "initials": "A"}, {"family": "Kullander", "given": "Klas", "initials": "K", "orcid": "0000-0001-6418-5460", "researcher": {"href": "https://publications.scilifelab.se/researcher/4d7f21b563e84264b0962dffd25953c3.json"}}, {"family": "Boije", "given": "Henrik", "initials": "H"}], "type": "journal article", "published": "2020-05-18", "journal": {"title": "eNeuro", "issn": "2373-2822", "issn-l": "2373-2822", "volume": "7", "issue": "3", "pages": "ENEURO.0047-20.2020"}, "abstract": "Vertebrate locomotion is orchestrated by spinal interneurons making up a central pattern generator. Proper coordination of activity, both within and between segments, is required to generate the desired locomotor output. This coordination is altered during acceleration to ensure the correct recruitment of muscles for the chosen speed. The transcription factor Dmrt3 has been proposed to shape the patterned output at different gaits in horses and mice. Here, we characterized dmrt3a mutant zebrafish, which showed a strong, transient, locomotor phenotype in developing larvae. During beat-and-glide swimming, mutant larvae showed fewer and shorter movements with decreased velocity and acceleration. Developmental compensation likely occurs as the analyzed behaviors did not differ from wild-type at older larval stages. However, analysis of maximum swim speed in juveniles suggests that some defects persist within the mature locomotor network of dmrt3a mutants. Our results reveal the pivotal role Dmrt3 neurons play in shaping the patterned output during acceleration in vertebrates.", "doi": "10.1523/ENEURO.0047-20.2020", "pmid": "32357958", "labels": {"Genome Engineering Zebrafish": "Service", "BioImage Informatics": "Service", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pii", "key": "ENEURO.0047-20.2020"}, {"db": "pmc", "key": "PMC7235372"}], "notes": [], "created": "2020-05-06T13:57:33.072Z", "modified": "2024-01-16T13:48:42.487Z"}, {"entity": "publication", "iuid": "943e2024538744c492d89c63c743f034", "links": {"self": {"href": "https://publications.scilifelab.se/publication/943e2024538744c492d89c63c743f034.json"}, "display": {"href": "https://publications.scilifelab.se/publication/943e2024538744c492d89c63c743f034"}}, "title": "Single cell transcriptomics identifies stem cell-derived graft composition in a model of Parkinson's disease.", "authors": [{"family": "Tiklov\u00e1", "given": "Katar\u00edna", "initials": "K"}, {"family": "Nolbrant", "given": "Sara", "initials": "S", "orcid": "0000-0003-2184-1741", "researcher": {"href": "https://publications.scilifelab.se/researcher/91ab50f5e5874992a0703470230a8462.json"}}, {"family": "Fiorenzano", "given": "Alessandro", "initials": "A"}, {"family": "Bj\u00f6rklund", "given": "\u00c5sa K", "initials": "\u00c5K", "orcid": "0000-0003-2224-7090", "researcher": {"href": "https://publications.scilifelab.se/researcher/8eb8c1fc5f704cbfb87471226485ae1f.json"}}, {"family": "Sharma", "given": "Yogita", "initials": "Y"}, {"family": "Heuer", "given": "Andreas", "initials": "A", "orcid": "0000-0003-0300-7606", "researcher": {"href": "https://publications.scilifelab.se/researcher/fc2bac2f0e63487792fd5525ee1c2b1e.json"}}, {"family": "Gillberg", "given": "Linda", "initials": "L"}, {"family": "Hoban", "given": "Deirdre B", "initials": "DB"}, {"family": "Cardoso", "given": "Tiago", "initials": "T", "orcid": "0000-0003-2686-458X", "researcher": {"href": "https://publications.scilifelab.se/researcher/08d76d0b77f14d39a6c097386e158174.json"}}, {"family": "Adler", "given": "Andrew F", "initials": "AF"}, {"family": "Birtele", "given": "Marcella", "initials": "M"}, {"family": "Lund\u00e9n-Miguel", "given": "Hilda", "initials": "H"}, {"family": "Volakakis", "given": "Nikolaos", "initials": "N"}, {"family": "Kirkeby", "given": "Agnete", "initials": "A"}, {"family": "Perlmann", "given": "Thomas", "initials": "T"}, {"family": "Parmar", "given": "Malin", "initials": "M", "orcid": "0000-0001-5002-4199", "researcher": {"href": "https://publications.scilifelab.se/researcher/c48b5aaff3bc4832a96fda4f2cf127cb.json"}}], "type": "journal article", "published": "2020-05-15", "journal": {"volume": "11", "issn": "2041-1723", "issue": "1", "pages": "2434", "title": "Nat Commun", "issn-l": "2041-1723"}, "abstract": "Cell replacement is a long-standing and realistic goal for the treatment of Parkinson's disease (PD). Cells for transplantation can be obtained from fetal brain tissue or from stem cells. However, after transplantation, dopamine (DA) neurons are seen to be a minor component of grafts, and it has remained difficult to determine the identity of other cell types. Here, we report analysis by single-cell RNA sequencing (scRNA-seq) combined with comprehensive histological analyses to characterize intracerebral grafts from human embryonic stem cells (hESCs) and fetal tissue after functional maturation in a pre-clinical rat PD model. We show that neurons and astrocytes are major components in both fetal and stem cell-derived grafts. Additionally, we identify a cell type closely resembling a class of recently identified perivascular-like cells in stem cell-derived grafts. Thus, this study uncovers previously unknown cellular diversity in a clinically relevant cell replacement PD model.", "doi": "10.1038/s41467-020-16225-5", "pmid": "32415072", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-16225-5"}, {"db": "pmc", "key": "PMC7229159"}], "notes": [], "created": "2020-06-02T07:25:59.289Z", "modified": "2024-01-16T13:48:42.494Z"}, {"entity": "publication", "iuid": "00954388bf944b23a0de53ff10845a71", "links": {"self": {"href": "https://publications.scilifelab.se/publication/00954388bf944b23a0de53ff10845a71.json"}, "display": {"href": "https://publications.scilifelab.se/publication/00954388bf944b23a0de53ff10845a71"}}, "title": "Myocardial micro-biopsy procedure for molecular characterization with increased precision and reduced trauma.", "authors": [{"family": "Grankvist", "given": "Rikard", "initials": "R"}, {"family": "Chireh", "given": "Arvin", "initials": "A"}, {"family": "Sandell", "given": "Mikael", "initials": "M"}, {"family": "Mukarram", "given": "Abdul Kadir", "initials": "AK"}, {"family": "Jaff", "given": "Nasren", "initials": "N"}, {"family": "Berggren", "given": "Ingrid", "initials": "I"}, {"family": "Persson", "given": "Hans", "initials": "H"}, {"family": "Linde", "given": "Cecilia", "initials": "C"}, {"family": "Arnberg", "given": "Fabian", "initials": "F"}, {"family": "Lundberg", "given": "Johan", "initials": "J"}, {"family": "Ugander", "given": "Martin", "initials": "M"}, {"family": "La Manno", "given": "Gioele", "initials": "G"}, {"family": "Jonsson", "given": "Stefan", "initials": "S"}, {"family": "Daub", "given": "Carsten O", "initials": "CO", "orcid": "0000-0002-3295-8729", "researcher": {"href": "https://publications.scilifelab.se/researcher/eda6a90f9d9046ada163d9843d169393.json"}}, {"family": "Holmin", "given": "Staffan", "initials": "S"}], "type": "journal article", "published": "2020-05-15", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "8029", "issn-l": "2045-2322"}, "abstract": "Endomyocardial biopsy is a valuable tool in cardiac diagnostics but is limited by low diagnostic yield and significant complication risks. Meanwhile, recent developments in transcriptomic and proteomic technologies promise a wealth of biological data from minimal tissue samples. To take advantage of the minimal tissue amount needed for molecular analyses, we have developed a sub-millimeter endovascular biopsy device, considerably smaller than current clinical equipment, and devised a low-input RNA-sequencing protocol for analyzing small tissue samples. In in vivo evaluation in swine, 81% of biopsy attempts (n = 157) were successful. High quality RNA-sequencing data was generated from 91% of the sequenced cardiac micro-biopsy samples (n = 32). Gene expression signatures of samples taken with the novel device were comparable with a conventional device. No major complications were detected either during procedures or during 7 days' follow-up, despite acquiring a relatively large number of biopsies (median 30) in each animal. In conclusion, the novel device coupled with RNA-sequencing provides a feasible method to obtain molecular data from the myocardium. The method is less traumatic and has a higher flexibility compared to conventional methods, enabling safer and more targeted sampling from different parts of the myocardium.", "doi": "10.1038/s41598-020-64900-w", "pmid": "32415191", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-64900-w"}, {"db": "pmc", "key": "PMC7229024"}], "notes": [], "created": "2020-07-08T13:04:40.159Z", "modified": "2024-01-16T13:48:42.501Z"}, {"entity": "publication", "iuid": "72e9b85908ed435d8265e945883e4b04", "links": {"self": {"href": "https://publications.scilifelab.se/publication/72e9b85908ed435d8265e945883e4b04.json"}, "display": {"href": "https://publications.scilifelab.se/publication/72e9b85908ed435d8265e945883e4b04"}}, "title": "Alterations of endometrial epithelial-mesenchymal transition and MAPK signalling components in women with PCOS are partially modulated by metformin in vitro.", "authors": [{"family": "Hu", "given": "Min", "initials": "M"}, {"family": "Zhang", "given": "Yuehui", "initials": "Y"}, {"family": "Li", "given": "Xin", "initials": "X"}, {"family": "Cui", "given": "Peng", "initials": "P"}, {"family": "Li", "given": "Juan", "initials": "J"}, {"family": "Br\u00e4nnstr\u00f6m", "given": "Mats", "initials": "M"}, {"family": "Shao", "given": "Linus R", "initials": "LR"}, {"family": "Billig", "given": "H\u00e5kan", "initials": "H"}], "type": "journal article", "published": "2020-05-15", "journal": {"title": "Mol. Hum. Reprod.", "issn": "1460-2407", "volume": "26", "issue": "5", "pages": "312-326", "issn-l": "1360-9947"}, "abstract": "Growing evidence suggests that epithelial-mesenchymal transition (EMT) and its regulator mitogen-activated protein kinase (MAPK) contribute to endometria-related reproductive disorders. However, the regulation of EMT and MAPK signalling components in the endometrium from polycystic ovary syndrome (PCOS) patients has not been systematically investigated and remains elusive. In humans, how metformin induces molecular alterations in the endometrial tissues under PCOS conditions is not completely clear. Here, we recruited 7 non-PCOS patients during the proliferative phase (nPCOS), 7 non-PCOS patients with endometrial hyperplasia (nPCOSEH), 14 PCOS patients during the proliferative phase (PCOS) and 3 PCOS patients with endometrial hyperplasia (PCOSEH). Our studies demonstrated that compared with nPCOS, PCOS patients showed decreased Claudin 1 and increased Vimentin and Slug proteins. Similar to increased Slug protein, nPCOSEH and PCOSEH patients showed increased N-cadherin protein. Western blot and immunostaining revealed increased epithelial phosphorylated Cytokeratin 8 (p-CK 8) expression and an increased p-CK 8:CK 8 ratio in PCOS, nPCOSEH and PCOSEH patients compared to nPCOS patients. Although nPCOSEH and PCOSEH patients showed increased p-ERK1/2 and/or p38 protein levels, the significant increase in p-ERK1/2 expression and p-ERK1/2:ERK1/2 ratio was only found in PCOS patients compared to nPCOS patients. A significant induction of the membrane ER\u03b2 immunostaining was observed in the epithelial cells of PCOS and PCOSEH patients compared to nPCOS and nPCOSEH patients. While in vitro treatment with metformin alone increased Snail and decreased Claudin 1, N-cadherin and \u03b1-SMA proteins, concomitant treatment with metformin and E2 increased the expression of CK 8 and Snail proteins and decreased the expression of Claudin 1, ZO-1, Slug and \u03b1-SMA proteins. Our findings suggest that the EMT contributes to the switch from a healthy state to a PCOS state in the endometrium, which might subsequently drive endometrial injury and dysfunction. We also provide evidence that metformin differentially modulates EMT protein expression in PCOS patients depending on oestrogenic stimulation.", "doi": "10.1093/molehr/gaaa023", "pmid": "32202622", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "5810989"}], "notes": [], "created": "2023-02-16T08:07:26.139Z", "modified": "2023-02-16T08:07:26.154Z"}, {"entity": "publication", "iuid": "5740889604b145baac1f446821f3da8d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5740889604b145baac1f446821f3da8d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5740889604b145baac1f446821f3da8d"}}, "title": "Integrative genomics approach identifies molecular features associated with early-stage ovarian carcinoma histotypes.", "authors": [{"family": "Engqvist", "given": "Hanna", "initials": "H"}, {"family": "Parris", "given": "Toshima Z", "initials": "TZ"}, {"family": "Biermann", "given": "Jana", "initials": "J"}, {"family": "R\u00f6nnerman", "given": "Elisabeth Werner", "initials": "EW"}, {"family": "Larsson", "given": "Peter", "initials": "P"}, {"family": "Sundfeldt", "given": "Karin", "initials": "K"}, {"family": "Kov\u00e1cs", "given": "Anik\u00f3", "initials": "A"}, {"family": "Karlsson", "given": "Per", "initials": "P"}, {"family": "Helou", "given": "Khalil", "initials": "K"}], "type": "journal article", "published": "2020-05-14", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "7946", "issn-l": "2045-2322"}, "abstract": "Ovarian cancer comprises multiple subtypes (clear-cell (CCC), endometrioid (EC), high-grade serous (HGSC), low-grade serous (LGSC), and mucinous carcinomas (MC)) with differing molecular and clinical behavior. However, robust histotype-specific biomarkers for clinical use have yet to be identified. Here, we utilized a multi-omics approach to identify novel histotype-specific genetic markers associated with ovarian carcinoma histotypes (CCC, EC, HGSC, and MC) using DNA methylation, DNA copy number alteration and RNA sequencing data for 96 primary invasive early-stage (stage I and II) ovarian carcinomas. More specifically, the DNA methylation analysis revealed hypermethylation for CCC in comparison with the other histotypes. Moreover, copy number imbalances and novel chromothripsis-like rearrangements (n = 64) were identified in ovarian carcinoma, with the highest number of chromothripsis-like patterns in HGSC. For the 1000 most variable transcripts, underexpression was most prominent for all histotypes in comparison with normal ovarian samples. Overall, the integrative approach identified 46 putative oncogenes (overexpressed, hypomethylated and DNA gain) and three putative tumor suppressor genes (underexpressed, hypermethylated and DNA loss) when comparing the different histotypes. In conclusion, the current study provides novel insights into molecular features associated with early-stage ovarian carcinoma that may improve patient stratification and subclassification of the histotypes.", "doi": "10.1038/s41598-020-64794-8", "pmid": "32409713", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-64794-8"}, {"db": "pmc", "key": "PMC7224294"}], "notes": [], "created": "2020-05-27T13:29:27.972Z", "modified": "2024-01-16T13:48:42.508Z"}, {"entity": "publication", "iuid": "a67f74b1dcdf445da4ec370ee216c8d6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a67f74b1dcdf445da4ec370ee216c8d6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a67f74b1dcdf445da4ec370ee216c8d6"}}, "title": "Genetic and environmental influences on human height from infancy through adulthood at different levels of parental education.", "authors": [{"family": "Jelenkovic", "given": "Aline", "initials": "A"}, {"family": "Sund", "given": "Reijo", "initials": "R", "orcid": "0000-0002-6268-8117", "researcher": {"href": "https://publications.scilifelab.se/researcher/27f81bab545a4b158866a08fe5263e08.json"}}, {"family": "Yokoyama", "given": "Yoshie", "initials": "Y"}, {"family": "Latvala", "given": "Antti", "initials": "A", "orcid": "0000-0001-5695-117X", "researcher": {"href": "https://publications.scilifelab.se/researcher/e675261bb7354ca782cc267262fbdaba.json"}}, {"family": "Sugawara", "given": "Masumi", "initials": "M"}, {"family": "Tanaka", "given": "Mami", "initials": "M"}, {"family": "Matsumoto", "given": "Satoko", "initials": "S"}, {"family": "Freitas", "given": "Duarte L", "initials": "DL"}, {"family": "Maia", "given": "Jos\u00e9 Antonio", "initials": "JA"}, {"family": "Knafo-Noam", "given": "Ariel", "initials": "A"}, {"family": "Mankuta", "given": "David", "initials": "D"}, {"family": "Abramson", "given": "Lior", "initials": "L"}, {"family": "Ji", "given": "Fuling", "initials": "F"}, {"family": "Ning", "given": "Feng", "initials": "F"}, {"family": "Pang", "given": "Zengchang", "initials": "Z"}, {"family": "Rebato", "given": "Esther", "initials": "E"}, {"family": "Saudino", "given": "Kimberly J", "initials": "KJ"}, {"family": "Cutler", "given": "Tessa L", "initials": "TL"}, {"family": "Hopper", "given": "John L", "initials": "JL"}, {"family": "Ullemar", "given": "Vilhelmina", "initials": "V"}, {"family": "Almqvist", "given": "Catarina", "initials": "C"}, {"family": "Magnusson", "given": "Patrik K E", "initials": "PKE", "orcid": "0000-0002-7315-7899", "researcher": {"href": "https://publications.scilifelab.se/researcher/b277b6387de142bbab91fad82d9eff09.json"}}, {"family": "Cozen", "given": "Wendy", "initials": "W"}, {"family": "Hwang", "given": "Amie E", "initials": "AE"}, {"family": "Mack", "given": "Thomas M", "initials": "TM"}, {"family": "Nelson", "given": "Tracy L", "initials": "TL"}, {"family": "Whitfield", "given": "Keith E", "initials": "KE"}, {"family": "Sung", "given": "Joohon", "initials": "J"}, {"family": "Kim", "given": "Jina", "initials": "J", "orcid": "0000-0003-1684-4219", "researcher": {"href": "https://publications.scilifelab.se/researcher/869e611833bc4f6aab2f47f540f89581.json"}}, {"family": "Lee", "given": "Jooyeon", "initials": "J", "orcid": "0000-0001-5220-0950", "researcher": {"href": "https://publications.scilifelab.se/researcher/b5e4b2f4f3b34e41a3901c90f6dc0ec2.json"}}, {"family": "Lee", "given": "Sooji", "initials": "S"}, {"family": "Llewellyn", "given": "Clare H", "initials": "CH", "orcid": "0000-0002-0066-2827", "researcher": {"href": "https://publications.scilifelab.se/researcher/97213af3e4704e13b608af74637dbb2e.json"}}, {"family": "Fisher", "given": "Abigail", "initials": "A"}, {"family": "Medda", "given": "Emanuela", "initials": "E"}, {"family": "Nistic\u00f2", "given": "Lorenza", "initials": "L", "orcid": "0000-0003-1805-6240", "researcher": {"href": "https://publications.scilifelab.se/researcher/c6a2e9c1a6a34419b4661afce3e01d3e.json"}}, {"family": "Toccaceli", "given": "Virgilia", "initials": "V"}, {"family": "Baker", "given": "Laura A", "initials": "LA"}, {"family": "Tuvblad", "given": "Catherine", "initials": "C"}, {"family": "Corley", "given": "Robin P", "initials": "RP"}, {"family": "Huibregtse", "given": "Brooke M", "initials": "BM", "orcid": "0000-0003-0977-7249", "researcher": {"href": "https://publications.scilifelab.se/researcher/e9df70acb87f443eb6da650b151a679c.json"}}, {"family": "Derom", "given": "Catherine A", "initials": "CA"}, {"family": "Vlietinck", "given": "Robert F", "initials": "RF"}, {"family": "Loos", "given": "Ruth J F", "initials": "RJF", "orcid": "0000-0002-8532-5087", "researcher": {"href": "https://publications.scilifelab.se/researcher/e5b6c24c302d42828806076ded81afe1.json"}}, {"family": "Burt", "given": "S Alexandra", "initials": "SA"}, {"family": "Klump", "given": "Kelly L", "initials": "KL"}, {"family": "Silberg", "given": "Judy L", "initials": "JL"}, {"family": "Maes", "given": "Hermine H", "initials": "HH"}, {"family": "Krueger", "given": "Robert F", "initials": "RF"}, {"family": "McGue", "given": "Matt", "initials": "M"}, {"family": "Pahlen", "given": "Shandell", "initials": "S"}, {"family": "Gatz", "given": "Margaret", "initials": "M"}, {"family": "Butler", "given": "David A", "initials": "DA"}, {"family": "Harris", "given": "Jennifer R", "initials": "JR"}, {"family": "Brandt", "given": "Ingunn", "initials": "I"}, {"family": "Nilsen", "given": "Thomas S", "initials": "TS"}, {"family": "Harden", "given": "K Paige", "initials": "KP"}, {"family": "Tucker-Drob", "given": "Elliot M", "initials": "EM"}, {"family": "Franz", "given": "Carol E", "initials": "CE", "orcid": "0000-0002-8987-1755", "researcher": {"href": "https://publications.scilifelab.se/researcher/4f24c335b7f544328bca9e9e73b8560e.json"}}, {"family": "Kremen", "given": "William S", "initials": "WS"}, {"family": "Lyons", "given": "Michael J", "initials": "MJ"}, {"family": "Lichtenstein", "given": "Paul", "initials": "P", "orcid": "0000-0003-3037-5287", "researcher": {"href": "https://publications.scilifelab.se/researcher/4db67c51837b4cdfa18cacbc3fca1173.json"}}, {"family": "Bartels", "given": "Meike", "initials": "M", "orcid": "0000-0002-9667-7555", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a91c095e993411b99e81e21f40d8597.json"}}, {"family": "Beijsterveldt", "given": "Catharina E M van", "initials": "CEMV", "orcid": "0000-0002-6617-4201", "researcher": {"href": "https://publications.scilifelab.se/researcher/6c3073fc4d1e4454bfc4bc7aad11b357.json"}}, {"family": "Willemsen", "given": "Gonneke", "initials": "G"}, {"family": "\u00d6ncel", "given": "Sevgi Y", "initials": "SY"}, {"family": "Aliev", "given": "Fazil", "initials": "F", "orcid": "0000-0001-8357-4699", "researcher": {"href": "https://publications.scilifelab.se/researcher/85556629452a4054bf7228b5f7049811.json"}}, {"family": "Jeong", "given": "Hoe-Uk", "initials": "HU"}, {"family": "Hur", "given": "Yoon-Mi", "initials": "YM"}, {"family": "Turkheimer", "given": "Eric", "initials": "E"}, {"family": "Boomsma", "given": "Dorret I", "initials": "DI", "orcid": "0000-0002-7099-7972", "researcher": {"href": "https://publications.scilifelab.se/researcher/4b66ab2525fd4a468e7a4ad14c955cb4.json"}}, {"family": "S\u00f8rensen", "given": "Thorkild I A", "initials": "TIA", "orcid": "0000-0003-4821-430X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3495a648342a491d9105817cc30d5d56.json"}}, {"family": "Kaprio", "given": "Jaakko", "initials": "J", "orcid": "0000-0002-3716-2455", "researcher": {"href": "https://publications.scilifelab.se/researcher/814d362333844b72a70cba9ebcf61e6f.json"}}, {"family": "Silventoinen", "given": "Karri", "initials": "K"}], "type": "journal article", "published": "2020-05-14", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "7974", "issn-l": "2045-2322"}, "abstract": "Genetic factors explain a major proportion of human height variation, but differences in mean stature have also been found between socio-economic categories suggesting a possible effect of environment. By utilizing a classical twin design which allows decomposing the variation of height into genetic and environmental components, we tested the hypothesis that environmental variation in height is greater in offspring of lower educated parents. Twin data from 29 cohorts including 65,978 complete twin pairs with information on height at ages 1 to 69 years and on parental education were pooled allowing the analyses at different ages and in three geographic-cultural regions (Europe, North America and Australia, and East Asia). Parental education mostly showed a positive association with offspring height, with significant associations in mid-childhood and from adolescence onwards. In variance decomposition modeling, the genetic and environmental variance components of height did not show a consistent relation to parental education. A random-effects meta-regression analysis of the aggregate-level data showed a trend towards greater shared environmental variation of height in low parental education families. In conclusion, in our very large dataset from twin cohorts around the globe, these results provide only weak evidence for the study hypothesis.", "doi": "10.1038/s41598-020-64883-8", "pmid": "32409744", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-64883-8"}, {"db": "pmc", "key": "PMC7224277"}], "notes": [], "created": "2020-05-27T13:29:27.487Z", "modified": "2021-11-10T12:51:04.364Z"}, {"entity": "publication", "iuid": "a8d5da0c1a824033afd877d589b71e66", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a8d5da0c1a824033afd877d589b71e66.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a8d5da0c1a824033afd877d589b71e66"}}, "title": "Interphase Design of Cellulose Nanocrystals/Poly(hydroxybutyrate-ran-valerate) Bionanocomposites for Mechanical and Thermal Properties Tuning.", "authors": [{"family": "Magnani", "given": "Chiara", "initials": "C", "orcid": "0000-0003-0858-6264", "researcher": {"href": "https://publications.scilifelab.se/researcher/68990aaef32342f0a6f1982dc7d8c281.json"}}, {"family": "Idstr\u00f6m", "given": "Alexander", "initials": "A", "orcid": "0000-0003-4765-8224", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e9c71cee50545969b1d2167c8d03f43.json"}}, {"family": "Nordstierna", "given": "Lars", "initials": "L", "orcid": "0000-0002-6580-0610", "researcher": {"href": "https://publications.scilifelab.se/researcher/9d5546ed87b0480aae72d8574db96911.json"}}, {"family": "M\u00fcller", "given": "Alejandro J", "initials": "AJ", "orcid": "0000-0001-7009-7715", "researcher": {"href": "https://publications.scilifelab.se/researcher/d847bee63302496eab7e36b9b8e3ae4f.json"}}, {"family": "Dubois", "given": "Philippe", "initials": "P", "orcid": "0000-0003-1534-1564", "researcher": {"href": "https://publications.scilifelab.se/researcher/a050299d8d9c4ae089858b172b0a9e26.json"}}, {"family": "Raquez", "given": "Jean-Marie", "initials": "JM", "orcid": "0000-0003-1940-7129", "researcher": {"href": "https://publications.scilifelab.se/researcher/410c469cfcc5478b96eda30c3b765b8f.json"}}, {"family": "Lo Re", "given": "Giada", "initials": "G", "orcid": "0000-0001-8840-1172", "researcher": {"href": "https://publications.scilifelab.se/researcher/ec9d6813b34747399c8cef90a63a8c4e.json"}}], "type": "journal article", "published": "2020-05-11", "journal": {"title": "Biomacromolecules", "issn": "1526-4602", "volume": "21", "issue": "5", "pages": "1892-1901", "issn-l": "1525-7797"}, "abstract": "Poly[(3-hydroxybutyrate)-ran-(3-hydroxyvalerate)] (PHBV) is a bacterial polyester with a strong potential as a substitute for oil-based thermoplastics due to its biodegradability and renewability. However, its inherent slow crystallization rate limits its thermomechanical properties and therefore its applications. In this work, surface-modified cellulose nanocrystals (CNCs) have been investigated as green and biosourced nucleating and reinforcing agent for PHBV matrix. Different ester moieties from the CNCs were thereby produced through a green one-pot hydrolysis/Fisher esterification. Beyond the improved dispersion, the CNCs surface esterification affected the thermal and thermomechanical properties of PHBV. The results demonstrate that butyrate-modified CNCs, mimicking the PHBV chemical structure, brought a considerable improvement toward the CNCs/matrix interface, leading to an enhancement of the PHBV thermomechanical properties via a more efficient stress transfer, especially above its glass transition.", "doi": "10.1021/acs.biomac.9b01760", "pmid": "32078304", "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [], "notes": [], "created": "2020-12-11T09:08:38.511Z", "modified": "2025-10-17T13:03:56.913Z"}, {"entity": "publication", "iuid": "0c07a28bbb914669b744e2bd22a9d0c8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0c07a28bbb914669b744e2bd22a9d0c8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0c07a28bbb914669b744e2bd22a9d0c8"}}, "title": "Altered Thermal and Mechanical Properties of Spruce Galactoglucomannan Films Modified with an Etherification Reaction.", "authors": [{"family": "H\u00e4rdelin", "given": "Linda", "initials": "L", "orcid": "0000-0003-0463-6834", "researcher": {"href": "https://publications.scilifelab.se/researcher/38cba73a60554c02be7a1237e8249910.json"}}, {"family": "Bernin", "given": "Diana", "initials": "D", "orcid": "0000-0002-9611-2263", "researcher": {"href": "https://publications.scilifelab.se/researcher/7ad134b1d8ab41b8a8a3318801d92e10.json"}}, {"family": "B\u00f6rjesson", "given": "Mikaela", "initials": "M"}, {"family": "Str\u00f6m", "given": "Anna", "initials": "A", "orcid": "0000-0002-9743-1514", "researcher": {"href": "https://publications.scilifelab.se/researcher/c7513a32dfe349049ce59af16ceb5be6.json"}}, {"family": "Larsson", "given": "Anette", "initials": "A", "orcid": "0000-0002-6119-8423", "researcher": {"href": "https://publications.scilifelab.se/researcher/23144308775945c0b4aa3d6a4a39c353.json"}}], "type": "journal article", "published": "2020-05-11", "journal": {"title": "Biomacromolecules", "issn": "1526-4602", "volume": "21", "issue": "5", "pages": "1832-1840", "issn-l": "1525-7797"}, "abstract": "Native hemicellulose lacks many of the properties that make fossil fuel-based polymers excellent for use in today's industrial products and processes. The mechanical and thermal properties of the hemicellulose can, however, be modified, and its processability increased. We functionalized galactoglucomannan to lower its glass transition temperature (Tg) and thereby increase its processability. The functionalization was achieved through an etherification reaction with butyl glycidyl ether used at three molar ratios. Films were produced, and their mechanical and thermal properties were evaluated. Thermogravimetric analysis showed that increased substitution increased the degradation temperature and decreased the water content in the sample, implying increased hydrophobicity upon modification. Dynamic mechanical analysis indicated that butyl glycidyl ether functionalization alters the thermal properties of the modified films both in the absolute values of Tg and in the strength of the films. The etherification reaction resulted in a more ductile material than the unmodified galactoglucomannan (GGM).", "doi": "10.1021/acs.biomac.9b01730", "pmid": "32068390", "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [], "notes": [], "created": "2020-12-11T09:11:22.886Z", "modified": "2025-10-17T13:03:56.928Z"}, {"entity": "publication", "iuid": "a8185c111fd34c76a142beed9b5d494a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a8185c111fd34c76a142beed9b5d494a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a8185c111fd34c76a142beed9b5d494a"}}, "title": "Srebf1 Controls Midbrain Dopaminergic Neurogenesis.", "authors": [{"family": "Toledo", "given": "Enrique M", "initials": "EM"}, {"family": "Yang", "given": "Shanzheng", "initials": "S"}, {"family": "Gyllborg", "given": "Daniel", "initials": "D"}, {"family": "van Wijk", "given": "Kim E", "initials": "KE"}, {"family": "Sinha", "given": "Indranil", "initials": "I"}, {"family": "Varas-Godoy", "given": "Manuel", "initials": "M"}, {"family": "Grigsby", "given": "Christopher L", "initials": "CL"}, {"family": "L\u00f6nnerberg", "given": "Peter", "initials": "P"}, {"family": "Islam", "given": "Saiful", "initials": "S"}, {"family": "Steffensen", "given": "Knut R", "initials": "KR"}, {"family": "Linnarsson", "given": "Sten", "initials": "S"}, {"family": "Arenas", "given": "Ernest", "initials": "E"}], "type": "journal article", "published": "2020-05-05", "journal": {"title": "Cell Rep", "issn": "2211-1247", "volume": "31", "issue": "5", "pages": "107601", "issn-l": null}, "abstract": "Liver X receptors (LXRs) and their ligands are potent regulators of midbrain dopaminergic (mDA) neurogenesis and differentiation. However, the molecular mechanisms by which LXRs control these functions remain to be elucidated. Here, we perform a combined transcriptome and chromatin immunoprecipitation sequencing (ChIP-seq) analysis of midbrain cells after LXR activation, followed by bioinformatic analysis to elucidate the transcriptional networks controlling mDA neurogenesis. Our results identify the basic helix-loop-helix transcription factor sterol regulatory element binding protein 1 (SREBP1) as part of a cluster of proneural transcription factors in radial glia and as a regulator of transcription factors controlling mDA neurogenesis, such as Foxa2. Moreover, loss- and gain-of-function experiments in vitro and in vivo demonstrate that Srebf1 is both required and sufficient for mDA neurogenesis. Our data, thus, identify Srebf1 as a central player in mDA neurogenesis.", "doi": "10.1016/j.celrep.2020.107601", "pmid": "32375051", "labels": {"NGI Stockholm (Genomics Applications)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S2211-1247(20)30550-7"}], "notes": [], "created": "2021-01-08T16:29:13.408Z", "modified": "2024-01-16T13:48:42.515Z"}, {"entity": "publication", "iuid": "b4fea37d05cc4e49aed01a6e67fdc74d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b4fea37d05cc4e49aed01a6e67fdc74d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b4fea37d05cc4e49aed01a6e67fdc74d"}}, "title": "High-Resolution In Situ NMR Spectroscopy of Bacterial Envelope Proteins in Outer Membrane Vesicles.", "authors": [{"family": "Thoma", "given": "Johannes", "initials": "J"}, {"family": "Burmann", "given": "Bj\u00f6rn M", "initials": "BM", "orcid": "0000-0002-3135-7964", "researcher": {"href": "https://publications.scilifelab.se/researcher/b7a6d61fc1a64677874973c3247b1eb4.json"}}], "type": "journal article", "published": "2020-05-05", "journal": {"title": "Biochemistry", "issn": "1520-4995", "volume": "59", "issue": "17", "pages": "1656-1660", "issn-l": "0006-2960"}, "abstract": "The cell envelope of Gram-negative bacteria is an elaborate cellular environment, consisting of two lipid membranes separated by the aqueous periplasm. So far, efforts to mimic this environment under laboratory conditions have been limited by the complexity of the asymmetric bacterial outer membrane. To evade this impasse, we recently established a method to modify the protein composition of bacterial outer membrane vesicles (OMVs) released from Escherichia coli as a platform for biophysical studies of outer membrane proteins in their native membrane environment. Here, we apply protein-enriched OMVs to characterize the structure of three envelope proteins from E. coli using nuclear magnetic resonance (NMR) spectroscopy and expand the methodology to soluble periplasmic proteins. We obtain high-resolution in situ NMR spectra of the transmembrane protein OmpA as well as the periplasmic proteins CpxP and MalE. We find that our approach facilitates structural investigations of membrane-attached protein domains and is especially suited for soluble proteins within their native periplasmic environment. Thereby, the use of OMVs in solution NMR methods allows in situ analysis of the structure and dynamics of proteins twice the size compared to the current in-cell NMR methodology. We therefore expect our work to pave the way for more complex NMR studies of bacterial envelope proteins in the native environment of OMVs in the future.", "doi": "10.1021/acs.biochem.9b01123", "pmid": "32233422", "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7310948"}], "notes": [], "created": "2020-12-11T09:04:33.985Z", "modified": "2025-10-17T13:03:56.944Z"}, {"entity": "publication", "iuid": "f4427096b88f41f3962469e06754180d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f4427096b88f41f3962469e06754180d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f4427096b88f41f3962469e06754180d"}}, "title": "A progressive and complex clinical course in two family members with ERF-related craniosynostosis: a case report.", "authors": [{"family": "K\u00f6rberg", "given": "Izabella", "initials": "I"}, {"family": "Nowinski", "given": "Daniel", "initials": "D"}, {"family": "Bondeson", "given": "Marie-Louise", "initials": "ML"}, {"family": "Melin", "given": "Malin", "initials": "M", "orcid": "0000-0002-6589-2375", "researcher": {"href": "https://publications.scilifelab.se/researcher/190c3991975c43ec952a81df72292c9a.json"}}, {"family": "K\u00f6lby", "given": "Lars", "initials": "L"}, {"family": "Stattin", "given": "Eva-Lena", "initials": "EL"}], "type": "case reports", "published": "2020-05-05", "journal": {"title": "BMC Med. Genet.", "issn": "1471-2350", "volume": "21", "issue": "1", "pages": "90", "issn-l": "1471-2350"}, "abstract": "ERF-related craniosynostosis are a rare, complex, premature trisutural fusion associated with a broad spectrum of clinical features and heterogeneous aetiology. Here we describe two cases with the same pathogenic variant and a detailed description of their clinical course.\n\nTwo subjects; a boy with a BLSS requiring repeated skull expansions and his mother who had been operated once for sagittal synostosis. Both developed intracranial hypertension at some point during the course, which was for both verified by formal invasive intracranial pressure monitoring. Exome sequencing revealed a pathogenic truncating frame shift variant in the ERF gene.\n\nHere we describe a boy and his mother with different craniosynostosis patterns, but both with verified intracranial hypertension and heterozygosity for a truncating variant of ERF c.1201_1202delAA (p.Lys401Glufs*10). Our work provides supplementary evidence in support of previous phenotypic descriptions of ERF-related craniosynostosis, particularly late presentation, an evolving synostotic pattern and variable expressivity even among affected family members.", "doi": "10.1186/s12881-020-01015-z", "pmid": "32370745", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Clinical Genomics Uppsala": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1186/s12881-020-01015-z"}, {"db": "pmc", "key": "PMC7201657"}], "notes": [], "created": "2020-05-11T22:07:48.851Z", "modified": "2021-12-06T08:29:24.182Z"}, {"entity": "publication", "iuid": "112965c0f79145bb91da7dfa37d0dd1f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/112965c0f79145bb91da7dfa37d0dd1f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/112965c0f79145bb91da7dfa37d0dd1f"}}, "title": "Lipid accumulation controls the balance between surface connection and scission of caveolae.", "authors": [{"family": "Hubert", "given": "Madlen", "initials": "M"}, {"family": "Larsson", "given": "Elin", "initials": "E"}, {"family": "Vegesna", "given": "Naga Venkata Gayathri", "initials": "NVG"}, {"family": "Ahnlund", "given": "Maria", "initials": "M"}, {"family": "Johansson", "given": "Annika I", "initials": "AI", "orcid": "0000-0001-5000-1288", "researcher": {"href": "https://publications.scilifelab.se/researcher/0b0835b94db946929c1cb0c8f9319068.json"}}, {"family": "Moodie", "given": "Lindon Wk", "initials": "LW"}, {"family": "Lundmark", "given": "Richard", "initials": "R", "orcid": "0000-0001-9104-724X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3e1b756caa79468dab0f960e43cd61d3.json"}}], "type": "comparative study", "published": "2020-05-04", "journal": {"title": "Elife", "issn": "2050-084X", "issn-l": "2050-084X", "volume": "9", "issue": null, "pages": null}, "abstract": "Caveolae are bulb-shaped invaginations of the plasma membrane (PM) that undergo scission and fusion at the cell surface and are enriched in specific lipids. However, the influence of lipid composition on caveolae surface stability is not well described or understood. Accordingly, we inserted specific lipids into the cell PM via membrane fusion and studied their acute effects on caveolae dynamics. We demonstrate that sphingomyelin stabilizes caveolae to the cell surface, whereas cholesterol and glycosphingolipids drive caveolae scission from the PM. Although all three lipids accumulated specifically in caveolae, cholesterol and sphingomyelin were actively sequestered, whereas glycosphingolipids diffused freely. The ATPase EHD2 restricts lipid diffusion and counteracts lipid-induced scission. We propose that specific lipid accumulation in caveolae generates an intrinsically unstable domain prone to scission if not restrained by EHD2 at the caveolae neck. This work provides a mechanistic link between caveolae and their ability to sense the PM lipid composition.", "doi": "10.7554/eLife.55038", "pmid": "32364496", "labels": {"Integrated Microscopy Technologies Ume\u00e5": "Collaborative", "Swedish Metabolomics Centre": "Collaborative"}, "xrefs": [{"db": "pii", "key": "55038"}, {"db": "pmc", "key": "PMC7239661"}], "notes": [], "created": "2020-12-11T12:02:15.906Z", "modified": "2025-10-17T13:03:16.859Z"}, {"entity": "publication", "iuid": "7eec3c7141e540bfbf96f05692cc6378", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7eec3c7141e540bfbf96f05692cc6378.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7eec3c7141e540bfbf96f05692cc6378"}}, "title": "Rare variants in dynein heavy chain genes in two individuals with situs inversus and developmental dyslexia: a case report.", "authors": [{"family": "Bieder", "given": "Andrea", "initials": "A"}, {"family": "Einarsdottir", "given": "Elisabet", "initials": "E"}, {"family": "Matsson", "given": "Hans", "initials": "H"}, {"family": "Nilsson", "given": "Harriet E", "initials": "HE"}, {"family": "Eisfeldt", "given": "Jesper", "initials": "J"}, {"family": "Dragomir", "given": "Anca", "initials": "A"}, {"family": "Paucar", "given": "Martin", "initials": "M"}, {"family": "Granberg", "given": "Tobias", "initials": "T"}, {"family": "Li", "given": "Tie-Qiang", "initials": "TQ"}, {"family": "Lindstrand", "given": "Anna", "initials": "A"}, {"family": "Kere", "given": "Juha", "initials": "J"}, {"family": "Tapia-P\u00e1ez", "given": "Isabel", "initials": "I"}], "type": "case reports", "published": "2020-05-01", "journal": {"title": "BMC Med. Genet.", "issn": "1471-2350", "volume": "21", "issue": "1", "pages": "87", "issn-l": "1471-2350"}, "abstract": "Developmental dyslexia (DD) is a neurodevelopmental learning disorder with high heritability. A number of candidate susceptibility genes have been identified, some of which are linked to the function of the cilium, an organelle regulating left-right asymmetry development in the embryo. Furthermore, it has been suggested that disrupted left-right asymmetry of the brain may play a role in neurodevelopmental disorders such as DD. However, it is unknown whether there is a common genetic cause to DD and laterality defects or ciliopathies.\n\nHere, we studied two individuals with co-occurring situs inversus (SI) and DD using whole genome sequencing to identify genetic variants of importance for DD and SI. Individual 1 had primary ciliary dyskinesia (PCD), a rare, autosomal recessive disorder with oto-sino-pulmonary phenotype and SI. We identified two rare nonsynonymous variants in the dynein axonemal heavy chain 5 gene (DNAH5): a previously reported variant c.7502G > C; p.(R2501P), and a novel variant c.12043 T > G; p.(Y4015D). Both variants are predicted to be damaging. Ultrastructural analysis of the cilia revealed a lack of outer dynein arms and normal inner dynein arms. MRI of the brain revealed no significant abnormalities. Individual 2 had non-syndromic SI and DD. In individual 2, one rare variant (c.9110A > G;p.(H3037R)) in the dynein axonemal heavy chain 11 gene (DNAH11), coding for another component of the outer dynein arm, was identified.\n\nWe identified the likely genetic cause of SI and PCD in one individual, and a possibly significant heterozygosity in the other, both involving dynein genes. Given the present evidence, it is unclear if the identified variants also predispose to DD and further studies into the association between laterality, ciliopathies and DD are needed.", "doi": "10.1186/s12881-020-01020-2", "pmid": "32357925", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12881-020-01020-2"}, {"db": "pmc", "key": "PMC7193346"}], "notes": [], "created": "2020-07-08T13:04:09.826Z", "modified": "2021-11-10T12:51:23.871Z"}, {"entity": "publication", "iuid": "4b7ea1ee885748268299dace9908513e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4b7ea1ee885748268299dace9908513e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4b7ea1ee885748268299dace9908513e"}}, "title": "Molecular changes during progression from nonmuscle invasive to advanced urothelial carcinoma.", "authors": [{"family": "Sj\u00f6dahl", "given": "Gottfrid", "initials": "G", "orcid": "0000-0002-7869-0473", "researcher": {"href": "https://publications.scilifelab.se/researcher/8997407392384ebd9eaa2ee8ee4f1435.json"}}, {"family": "Eriksson", "given": "Pontus", "initials": "P"}, {"family": "Patschan", "given": "Oliver", "initials": "O"}, {"family": "Marzouka", "given": "Nour-Al-Dain", "initials": "NA"}, {"family": "Jakobsson", "given": "Lovisa", "initials": "L"}, {"family": "Bernardo", "given": "Carina", "initials": "C"}, {"family": "L\u00f6vgren", "given": "Kristina", "initials": "K"}, {"family": "Chebil", "given": "Gunilla", "initials": "G"}, {"family": "Zwarthoff", "given": "Ellen", "initials": "E"}, {"family": "Liedberg", "given": "Fredrik", "initials": "F"}, {"family": "H\u00f6glund", "given": "Mattias", "initials": "M"}], "type": "journal article", "published": "2020-05-01", "journal": {"title": "Int. J. Cancer", "issn": "1097-0215", "volume": "146", "issue": "9", "pages": "2636-2647", "issn-l": "0020-7136"}, "abstract": "Molecular changes occurring during invasion and clinical progression of cancer are difficult to study longitudinally in patient-derived material. A unique feature of urothelial bladder cancer (UBC) is that patients frequently develop multiple nonmuscle invasive tumors, some of which may eventually progress to invade the muscle of the bladder wall. Here, we use a cohort of 73 patients that experienced a total of 357 UBC diagnoses to study the stability or change in detected molecular alterations during cancer progression. The tumors were subtyped by gene expression profiling and analyzed for hotspot mutations in FGFR3, PIK3CA and TERT, the most frequent early driver mutations in this tumor type. TP53 alterations, frequent in advanced UBC, were inferred from p53 staining pattern, and potential genomic alterations were inferred by gene expression patterns at regions harboring frequent copy number alterations. We show that early driver mutations were largely preserved in UBC recurrences. Changes in FGFR3, PIK3CA or TERT mutation status were not linked to changes in molecular subtype and aggressive behavior. Instead, changes into a more aggressive molecular subtype seem to be associated with p53 alterations. We analyze changes in gene expression from primary tumors, to recurrences and progression tumors, and identify two modes of progression: Patients for whom progression is preceded by or coincides with a radical subtype shift, and patients who progress without any systematic molecular changes. For the latter group of patients, progression may be either stochastic or depending on factors already present at primary tumor initiation.", "doi": "10.1002/ijc.32737", "pmid": "31609466", "labels": {"Clinical Genomics Lund": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7079000"}], "notes": [], "created": "2021-11-25T09:36:06.632Z", "modified": "2021-11-25T09:36:06.692Z"}, {"entity": "publication", "iuid": "833e03625bc74a739758ff27bcb82ea2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/833e03625bc74a739758ff27bcb82ea2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/833e03625bc74a739758ff27bcb82ea2"}}, "title": "Isolation and characterization of microvesicles from mesenchymal stem cells.", "authors": [{"family": "Mohammadi", "given": "M Rezaa", "initials": "MR"}, {"family": "Riazifar", "given": "Milad", "initials": "M"}, {"family": "Pone", "given": "Egest J", "initials": "EJ"}, {"family": "Yeri", "given": "Ashish", "initials": "A"}, {"family": "Van Keuren-Jensen", "given": "Kendall", "initials": "K"}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C"}, {"family": "Lotvall", "given": "Jan", "initials": "J"}, {"family": "Zhao", "given": "Weian", "initials": "W"}], "type": "journal article", "published": "2020-05-01", "journal": {"title": "Methods", "issn": "1095-9130", "volume": "177", "issue": null, "pages": "50-57", "issn-l": "1046-2023"}, "abstract": "Mesenchymal stem or stromal cells are currently under clinical investigation for multiple diseases. While their mechanism of action is still not fully elucidated, vesicles secreted by MSCs are believed to recapitulate their therapeutic potentials to some extent. Microvesicles (MVs), also called as microparticles or ectosome, are among secreted vesicles that could transfer cytoplasmic cargo, including RNA and proteins, from emitting (source) cells to recipient cells. Given the importance of MVs, we here attempted to establish a method to isolate and characterize MVs secreted from unmodified human bone marrow derived MSCs (referred to as native MSCs, and their microvesicles as Native-MVs) and IFN\u03b3 stimulated MSCs (referred to as IFN\u03b3-MSCs, and their microvesicles as IFN\u03b3-MVs). We first describe an ultracentrifugation technique to isolate MVs from the conditioned cell culture media of MSCs. Next, we describe characterization and quality control steps to analyze the protein and RNA content of MVs. Finally, we examined the potential of MVs to exert immunomodulatory effects through induction of regulatory T cells (Tregs). Secretory vesicles from MSCs are promising alternatives for cell therapy with applications in drug delivery, regenerative medicine, and immunotherapy.", "doi": "10.1016/j.ymeth.2019.10.010", "pmid": "31669353", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "mid", "key": "NIHMS1542355"}, {"db": "pmc", "key": "PMC7182501"}, {"db": "pii", "key": "S1046-2023(19)30226-9"}], "notes": [], "created": "2020-01-23T16:11:25.279Z", "modified": "2023-02-16T08:08:22.362Z"}, {"entity": "publication", "iuid": "c0a96e98a034428a81aa4c4d641f4022", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c0a96e98a034428a81aa4c4d641f4022.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c0a96e98a034428a81aa4c4d641f4022"}}, "title": "Extracellular vesicles from mast cells induce mesenchymal transition in airway epithelial cells.", "authors": [{"family": "Yin", "given": "Yanan", "initials": "Y"}, {"family": "Shelke", "given": "Ganesh Vilas", "initials": "GV"}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C"}, {"family": "Brismar", "given": "Hjalmar", "initials": "H", "orcid": "0000-0003-0578-4003", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ec23336e2ef4e298f340876f1136dce.json"}}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J"}], "type": "journal article", "published": "2020-05-01", "journal": {"volume": "21", "issn": "1465-993X", "issue": "1", "pages": "101", "title": "Respir. Res.", "issn-l": "1465-9921"}, "abstract": "In the airways, mast cells are present in close vicinity to epithelial cells, and they can interact with each other via multiple factors, including extracellular vesicles (EVs). Mast cell-derived EVs have a large repertoire of cargos, including proteins and RNA, as well as surface DNA. In this study, we hypothesized that these EVs can induce epithelial to mesenchymal transition (EMT) in airway epithelial cells.\n\nIn this in-vitro study we systematically determined the effects of mast cell-derived EVs on epithelial A549 cells. We determined the changes that are induced by EVs on A549 cells at both the RNA and protein levels. Moreover, we also analyzed the rapid changes in phosphorylation events in EV-recipient A549 cells using a phosphorylated protein microarray. Some of the phosphorylation-associated events associated with EMT were validated using immunoblotting.\n\nMorphological and transcript analysis of epithelial A549 cells indicated that an EMT-like phenotype was induced by the EVs. Transcript analysis indicated the upregulation of genes involved in EMT, including TWIST1, MMP9, TGFB1, and BMP-7. This was accompanied by downregulation of proteins such as E-cadherin and upregulation of Slug-Snail and matrix metalloproteinases. Additionally, our phosphorylated-protein microarray analysis revealed proteins associated with the EMT cascade that were upregulated after EV treatment. We also found that transforming growth factor beta-1, a well-known EMT inducer, is associated with EVs and mediates the EMT cascade induced in the A549 cells.\n\nMast cell-derived EVs mediate the induction of EMT in epithelial cells, and our evidence suggests that this is triggered through the induction of protein phosphorylation cascades.", "doi": "10.1186/s12931-020-01346-8", "pmid": "32357878", "labels": {"Integrated Microscopy Technologies Stockholm": "Service", "Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7193353"}, {"db": "pii", "key": "10.1186/s12931-020-01346-8"}], "notes": [], "created": "2020-05-28T09:37:08.201Z", "modified": "2023-02-16T08:10:14.450Z"}, {"entity": "publication", "iuid": "daf757c012d548dd8bcf520909fc90d5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/daf757c012d548dd8bcf520909fc90d5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/daf757c012d548dd8bcf520909fc90d5"}}, "title": "Evolution of a New Function by Fusion between Phage DNA and a Bacterial Gene.", "authors": [{"family": "Warsi", "given": "Omar", "initials": "O"}, {"family": "Knopp", "given": "Michael", "initials": "M", "orcid": "0000-0002-8218-3263", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e2620cb646745b892428f758597f78e.json"}}, {"family": "Surkov", "given": "Serhiy", "initials": "S"}, {"family": "Jerlstr\u00f6m Hultqvist", "given": "Jon", "initials": "J"}, {"family": "Andersson", "given": "Dan I", "initials": "DI"}], "type": "journal article", "published": "2020-05-01", "journal": {"title": "Mol. Biol. Evol.", "issn": "1537-1719", "volume": "37", "issue": "5", "pages": "1329-1341", "issn-l": "0737-4038"}, "abstract": "Mobile genetic elements, such as plasmids, phages, and transposons, are important sources for evolution of novel functions. In this study, we performed a large-scale screening of metagenomic phage libraries for their ability to suppress temperature-sensitivity in Salmonella enterica serovar Typhimurium strain LT2 mutants to examine how phage DNA could confer evolutionary novelty to bacteria. We identified an insert encoding 23 amino acids from a phage that when fused with a bacterial DNA-binding repressor protein (LacI) resulted in the formation of a chimeric protein that localized to the outer membrane. This relocalization of the chimeric protein resulted in increased membrane vesicle formation and an associated suppression of the temperature sensitivity of the bacterium. Both the host LacI protein and the extracellular 23-amino acid stretch are necessary for the generation of the novel phenotype. Furthermore, mutational analysis of the chimeric protein showed that although the native repressor function of the LacI protein is maintained in this chimeric structure, it is not necessary for the new function. Thus, our study demonstrates how a gene fusion between foreign DNA and bacterial DNA can generate novelty without compromising the native function of a given gene.", "doi": "10.1093/molbev/msaa007", "pmid": "31977019", "labels": {"Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [{"db": "pii", "key": "5707441"}, {"db": "pmc", "key": "PMC7182210"}], "notes": [], "created": "2020-01-30T15:58:41.118Z", "modified": "2024-01-16T13:46:30.952Z"}, {"entity": "publication", "iuid": "342bc12c089c4c7fa2ac81719202f980", "links": {"self": {"href": "https://publications.scilifelab.se/publication/342bc12c089c4c7fa2ac81719202f980.json"}, "display": {"href": "https://publications.scilifelab.se/publication/342bc12c089c4c7fa2ac81719202f980"}}, "title": "Differential Expression of Immune Genes between Two Closely Related Beetle Species with Different Immunocompetence following Attack by Asecodes parviclava.", "authors": [{"family": "Yang", "given": "Xuyue", "initials": "X", "orcid": "0000-0003-2084-1651", "researcher": {"href": "https://publications.scilifelab.se/researcher/f0959fee187345d497cec63bce88d136.json"}}, {"family": "Fors", "given": "Lisa", "initials": "L"}, {"family": "Slotte", "given": "Tanja", "initials": "T", "orcid": "0000-0001-6020-5102", "researcher": {"href": "https://publications.scilifelab.se/researcher/67c69ee78bae41478465a7e5fa63b946.json"}}, {"family": "Theopold", "given": "Ulrich", "initials": "U"}, {"family": "Binzer-Panchal", "given": "Mahesh", "initials": "M"}, {"family": "Wheat", "given": "Christopher W", "initials": "CW"}, {"family": "Hamb\u00e4ck", "given": "Peter A", "initials": "PA"}], "type": "journal article", "published": "2020-05-01", "journal": {"title": "Genome Biol Evol", "issn": "1759-6653", "volume": "12", "issue": "5", "pages": "522-534", "issn-l": "1759-6653"}, "abstract": "Endoparasitoid wasps are important natural enemies of many insect species and are major selective forces on the host immune system. Despite increased interest in insect antiparasitoid immunity, there is sparse information on the evolutionary dynamics of biological pathways and gene regulation involved in host immune defense outside Drosophila species. We de novo assembled transcriptomes from two beetle species and used time-course differential expression analysis to investigate gene expression differences in closely related species Galerucella pusilla and G. calmariensis that are, respectively, resistant and susceptible against parasitoid infection by Asecodes parviclava parasitoids. Approximately 271 million and 224 million paired-ended reads were assembled and filtered to form 52,563 and 59,781 transcripts for G. pusilla and G. calmariensis, respectively. In the whole-transcriptome level, an enrichment of functional categories related to energy production, biosynthetic process, and metabolic process was exhibited in both species. The main difference between species appears to be immune response and wound healing process mounted by G. pusilla larvae. Using reciprocal BLAST against the Drosophila melanogaster proteome, 120 and 121 immune-related genes were identified in G. pusilla and G. calmariensis, respectively. More immune genes were differentially expressed in G. pusilla than in G. calmariensis, in particular genes involved in signaling, hematopoiesis, and melanization. In contrast, only one gene was differentially expressed in G. calmariensis. Our study characterizes important genes and pathways involved in different immune functions after parasitoid infection and supports the role of signaling and hematopoiesis genes as key players in host immunity in Galerucella against parasitoid wasps.", "doi": "10.1093/gbe/evaa075", "pmid": "32282901", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "5819554"}, {"db": "pmc", "key": "PMC7211424"}], "notes": [], "created": "2020-07-08T13:04:36.500Z", "modified": "2024-01-16T13:48:42.522Z"}, {"entity": "publication", "iuid": "342a9eea98eb46f1a43d7af5f008e709", "links": {"self": {"href": "https://publications.scilifelab.se/publication/342a9eea98eb46f1a43d7af5f008e709.json"}, "display": {"href": "https://publications.scilifelab.se/publication/342a9eea98eb46f1a43d7af5f008e709"}}, "title": "Whole-genome sequencing reveals complex chromosome rearrangement disrupting NIPBL in infant with Cornelia de Lange syndrome.", "authors": [{"family": "Plesser Duvdevani", "given": "Morasha", "initials": "M"}, {"family": "Pettersson", "given": "Maria", "initials": "M", "orcid": "0000-0003-3120-1625", "researcher": {"href": "https://publications.scilifelab.se/researcher/bfdfac2208ce4d1a877fa4957e2f4ea4.json"}}, {"family": "Eisfeldt", "given": "Jesper", "initials": "J"}, {"family": "Avraham", "given": "Ortal", "initials": "O"}, {"family": "Dagan", "given": "Judith", "initials": "J"}, {"family": "Frumkin", "given": "Ayala", "initials": "A", "orcid": "0000-0001-9103-9717", "researcher": {"href": "https://publications.scilifelab.se/researcher/5dd5f9cab2744569bd4d1c1ebc62945f.json"}}, {"family": "Lupski", "given": "James R", "initials": "JR", "orcid": "0000-0001-9907-9246", "researcher": {"href": "https://publications.scilifelab.se/researcher/88dd1dee9767489aaf25865670feb7b7.json"}}, {"family": "Lindstrand", "given": "Anna", "initials": "A"}, {"family": "Harel", "given": "Tamar", "initials": "T", "orcid": "0000-0003-3595-7075", "researcher": {"href": "https://publications.scilifelab.se/researcher/1f4e6a558c934ddd955531283e416a42.json"}}], "type": "case reports", "published": "2020-05-00", "journal": {"title": "Am. J. Med. Genet. A", "issn": "1552-4833", "volume": "182", "issue": "5", "pages": "1143-1151", "issn-l": "1552-4825"}, "abstract": "Clinical laboratory diagnostic evaluation of the genomes of children with suspected genetic disorders, including chromosomal microarray and exome sequencing, cannot detect copy number neutral genomic rearrangements such as inversions, balanced translocations, and complex chromosomal rearrangements (CCRs). We describe an infant with a clinical diagnosis of Cornelia de Lange syndrome (CdLS) in whom chromosome analysis revealed a de novo complex balanced translocation, 46,XY,t(5;7;6)(q11.2;q32;q13)dn. Subsequent molecular characterization by whole-genome sequencing (WGS) identified 23 breakpoints, delineating segments derived from four chromosomes (5;6;7;21) in ancestral or inverted orientation. One of the breakpoints disrupted a known CdLS gene, NIPBL. Further investigation revealed paternal origin of the CCR allele, clustering of the breakpoint junctions, and molecular repair signatures suggestive of a single catastrophic event. Notably, very short DNA segments (25 and 41 bp) were included in the reassembled chromosomes, lending additional support that the DNA repair machinery can detect and repair such segments. Interestingly, there was an independent paternally derived miniscule complex rearrangement, possibly predisposing to subsequent genomic instability. In conclusion, we report a CCR causing a monogenic Mendelian disorder, urging WGS analysis of similar unsolved cases with suspected Mendelian disorders. Breakpoint analysis allowed for identification of the underlying molecular diagnosis and implicated chromoanagenesis in CCR formation.", "doi": "10.1002/ajmg.a.61539", "pmid": "32125084", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7502196"}, {"db": "mid", "key": "NIHMS1625907"}], "notes": [], "created": "2020-07-08T13:05:13.646Z", "modified": "2024-01-16T13:48:42.530Z"}, {"entity": "publication", "iuid": "d70da1b632d44551ac3963b1a71b3694", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d70da1b632d44551ac3963b1a71b3694.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d70da1b632d44551ac3963b1a71b3694"}}, "title": "Whole-genome sequencing of human remains to enable genealogy DNA database searches - A case report.", "authors": [{"family": "Tillmar", "given": "Andreas", "initials": "A"}, {"family": "Sj\u00f6lund", "given": "Peter", "initials": "P"}, {"family": "Lundqvist", "given": "Bo", "initials": "B"}, {"family": "Klippmark", "given": "Therese", "initials": "T"}, {"family": "\u00c4lgen\u00e4s", "given": "Cajsa", "initials": "C"}, {"family": "Green", "given": "Henrik", "initials": "H"}], "type": "case reports", "published": "2020-05-00", "journal": {"title": "Forensic Sci Int Genet", "issn": "1878-0326", "volume": "46", "issue": null, "pages": "102233", "issn-l": "1872-4973"}, "abstract": "Recently a number of high profile crime cases (e.g. the \"Golden State Killer\") have successfully been solved or given new leads with the use of genome wide DNA data in combination with pairwise matching from individuals present in genealogy DNA databases. Such databases will primarily involve distant relatives which in turn require a large amount of genetic information, in the range of several hundred thousand to millions of SNPs, to be genotyped. While it nowadays is fairly straightforward to obtain such as data from high quality and high quantity DNA, it is still a challenge for degraded DNA of low quantity such in the case of forensic samples. Here we present a successful effort in obtaining genome-wide genotype data from human remains. The goal was to get investigative leads in order to identify the remains of an unknown male (\"the Ekeby man\") that was found murdered in the south of Sweden in 2003. Whole-genome sequencing was performed on DNA originating from a bone sample. Three replicates of libraries were prepared using ThruPLEX DNA-seq Kit (Takara) which were sequenced on a HiSeq X instrument (Illumina). A mean coverage of 30X was obtained when the sequencing reads were mapped to a human reference genome. Following further bioinformatic processing, allele calling, quality checks and filtering to match the genealogy DNA database SNPs, genotypes for approximately one million SNPs were established. The resulting SNP genotypes were then used to search for relatives in the genealogy DNA database GEDmatch (www.gedmatch.com). A candidate list of relatives was obtained which was further processed using traditional genealogy methods in order to get leads about the identity of the unknown. In summary, this report shows how whole-genome sequencing successfully can be applied on forensic samples to create the SNP genotypes required for searches in genealogy DNA databases for the purpose of generating leads to identify missing or unknown persons, including perpetrators and victims.", "doi": "10.1016/j.fsigen.2020.102233", "pmid": "31981902", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S1872-4973(20)30004-1"}], "notes": [], "created": "2020-12-08T23:48:02.849Z", "modified": "2024-01-16T13:48:42.537Z"}, {"entity": "publication", "iuid": "1db10b1c89f44f58a9844ca95744ecf0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1db10b1c89f44f58a9844ca95744ecf0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1db10b1c89f44f58a9844ca95744ecf0"}}, "title": "Transcriptome profiling of Ewing sarcomas - treatment resistance pathways and IGF-dependency.", "authors": [{"family": "Chen", "given": "Yi", "initials": "Y", "orcid": "0000-0002-4891-8289", "researcher": {"href": "https://publications.scilifelab.se/researcher/3ae866ca9a3244aba9678dc66a1e69e1.json"}}, {"family": "Hesla", "given": "Asle C", "initials": "AC"}, {"family": "Lin", "given": "Yingbo", "initials": "Y"}, {"family": "Ghaderi", "given": "Mehran", "initials": "M"}, {"family": "Liu", "given": "Mingzhi", "initials": "M"}, {"family": "Yang", "given": "Chen", "initials": "C"}, {"family": "Zhang", "given": "Yifan", "initials": "Y"}, {"family": "Tsagkozis", "given": "Panagiotis", "initials": "P"}, {"family": "Larsson", "given": "Olle", "initials": "O"}, {"family": "Haglund", "given": "Felix", "initials": "F", "orcid": "0000-0002-7015-3841", "researcher": {"href": "https://publications.scilifelab.se/researcher/891cbee146fa4e27bc8d26111283b854.json"}}], "type": "journal article", "published": "2020-05-00", "journal": {"title": "Mol Oncol", "issn": "1878-0261", "volume": "14", "issue": "5", "pages": "1101-1117", "issn-l": "1574-7891"}, "abstract": "Ewing sarcomas (ESs) are aggressive sarcomas driven by EWS fusion genes. We sought to investigate whether whole-transcriptome sequencing (RNA-seq) could be used to detect patterns associated with chemotherapy response or tumor progression after first-line treatment. Transcriptome sequencing (RNA-seq) of 13 ES cases was performed. Among the differentially expressed pathways, we identified IGF2 expression as a potential driver of chemotherapy response and progression. We investigated the effect of IGF2 on proliferation, radioresistance, apoptosis, and the transcriptome pattern in four ES cell lines and the effect of IGF2 expression in a validation series of 14 patients. Transcriptome analysis identified differentially expressed genes (adj. P < 0.005) and pathways associated with chemotherapy response (285 genes), short overall survival (662 genes), and progression after treatment (447 genes). Imprinting independent promoter P3-mediated IGF2 expression was identified in a subset of cases with aggressive clinical course. In ES cell lines, IGF2 induced proliferation, but promoted radioresistance only in CADO cells. High IGF2 expression was also significantly associated with shorter overall survival in patients with ES. Transcriptome analysis of the clinical samples and the cell lines revealed an IGF-dependent signature, potentially related to a stem cell-like phenotype. Transcriptome analysis is a potentially powerful complementary tool to predict the clinical behavior of ES and may be utilized for clinical trial stratification strategies and personalized oncology. Certain gene signatures, for example, IGF-related pathways, are coupled to biological functions that could be of clinical importance. Finally, our results indicate that IGF inhibition may be successful as a first-line therapy in conjunction with conventional radiochemotherapy for a subset of patients.", "doi": "10.1002/1878-0261.12655", "pmid": "32115849", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7191197"}], "notes": [], "created": "2020-07-08T13:04:54.124Z", "modified": "2024-01-16T13:48:42.546Z"}, {"entity": "publication", "iuid": "5ea3fa61d27c411cb95d6ae10c2cd99d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5ea3fa61d27c411cb95d6ae10c2cd99d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5ea3fa61d27c411cb95d6ae10c2cd99d"}}, "title": "SweHLA: the high confidence HLA typing bio-resource drawn from 1000 Swedish genomes.", "authors": [{"family": "Nordin", "given": "Jessika", "initials": "J", "orcid": "0000-0002-8414-2190", "researcher": {"href": "https://publications.scilifelab.se/researcher/2603df7f3ff84e6980605b9e8eef4c2f.json"}}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Lindblad-Toh", "given": "Kerstin", "initials": "K", "orcid": "0000-0001-8338-0253", "researcher": {"href": "https://publications.scilifelab.se/researcher/e0063145f7d6476f80ab42f94833f4cf.json"}}, {"family": "Gyllensten", "given": "Ulf", "initials": "U"}, {"family": "Meadows", "given": "Jennifer R S", "initials": "JRS"}], "type": "journal article", "published": "2020-05-00", "journal": {"title": "Eur. J. Hum. Genet.", "issn": "1476-5438", "issn-l": "1018-4813", "volume": "28", "issue": "5", "pages": "627-635"}, "abstract": "There is a need to accurately call human leukocyte antigen (HLA) genes from existing short-read sequencing data, however there is no single solution that matches the gold standard of Sanger sequenced lab typing. Here we aimed to combine results from available software programs, minimizing the biases of applied algorithm and HLA reference. The result is a robust HLA population resource for the published 1000 Swedish genomes, and a framework for future HLA interrogation. HLA 2nd-field alleles were called using four imputation and inference methods for the classical eight genes (class I: HLA-A, HLA-B, HLA-C; class II: HLA-DPA1, HLA-DPB1, HLA-DQA1, HLA-DQB1, HLA-DRB1). A high confidence population set (SweHLA) was determined using an n-1 concordance rule for class I (four software) and class II (three software) alleles. Results were compared across populations and individual programs benchmarked to SweHLA. Per gene, 875 to 988 of the 1000 samples were genotyped in SweHLA; 920 samples had at least seven loci called. While a small fraction of reference alleles were common to all software (class I = 1.9% and class II = 4.1%), this did not affect the overall call rate. Gene-level concordance was high compared to European populations (>0.83%), with COX and PGF the dominant SweHLA haplotypes. We noted that 15/18 discordant alleles (delta allele frequency >2) were previously reported as disease-associated. These differences could in part explain across-study genetic replication failures, reinforcing the need to use multiple software solutions. SweHLA demonstrates a way to use existing NGS data to generate a population resource agnostic to individual HLA software biases.", "doi": "10.1038/s41431-019-0559-2", "pmid": "31844174", "labels": {"National Genomics Infrastructure": "Collaborative", "NGI Uppsala (Uppsala Genome Center)": "Collaborative", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41431-019-0559-2"}, {"db": "pmc", "key": "PMC7170882"}], "notes": [], "created": "2020-02-11T10:04:25.991Z", "modified": "2021-11-10T12:51:33.748Z"}, {"entity": "publication", "iuid": "6c9f38d63146496e92771cf3dbfbd9e1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6c9f38d63146496e92771cf3dbfbd9e1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6c9f38d63146496e92771cf3dbfbd9e1"}}, "title": "Recurrent Fusions Between YAP1 and KMT2A in Morphologically Distinct Neoplasms Within the Spectrum of Low-grade Fibromyxoid Sarcoma and Sclerosing Epithelioid Fibrosarcoma.", "authors": [{"family": "Puls", "given": "Florian", "initials": "F"}, {"family": "Agaimy", "given": "Abbas", "initials": "A"}, {"family": "Flucke", "given": "Uta", "initials": "U"}, {"family": "Mentzel", "given": "Thomas", "initials": "T"}, {"family": "Sumathi", "given": "Vaiyapuri P", "initials": "VP"}, {"family": "Ploegmakers", "given": "Marieke", "initials": "M"}, {"family": "Stoehr", "given": "Robert", "initials": "R"}, {"family": "Kindblom", "given": "Lars-Gunnar", "initials": "LG"}, {"family": "Hansson", "given": "Magnus", "initials": "M"}, {"family": "Sydow", "given": "Saskia", "initials": "S"}, {"family": "Arbajian", "given": "Elsa", "initials": "E"}, {"family": "Mertens", "given": "Fredrik", "initials": "F"}], "type": "journal article", "published": "2020-05-00", "journal": {"title": "Am. J. Surg. Pathol.", "issn": "1532-0979", "volume": "44", "issue": "5", "pages": "594-606", "issn-l": "0147-5185"}, "abstract": "Sclerosing epithelioid fibrosarcoma (SEF) is an aggressive soft tissue sarcoma. In the majority of cases, there is overexpression of MUC4, and most cases show EWSR1-CREB3L1 gene fusions. A subset of SEF displays composite histologic features of SEF and low-grade fibromyxoid sarcoma (LGFMS). These \"hybrid\" tumors are more likely to harbor the FUS-CREB3L2 fusion, which is also seen in most LGFMS. We, here, characterize a series of 8 soft tissue neoplasms with morphologic features highly overlapping with LGFMS and SEF but lacking MUC4 expression and EWSR1/FUS-CREB3L gene fusions. Seven tumors showed fusions of the YAP1 and KMT2A genes, and 1 had a fusion of PRRX1 and KMT2D; all but 1 case displayed reciprocal gene fusions. At gene expression profiling, YAP1 and KMT2A/PRRX1 and KMT2D tumors were distinct from LGFMS/SEF. The patients were 4 female individuals and 4 male individuals aged 11 to 91 years. Tumors with known locations were in the lower extremity (5), trunk (2), and upper extremity (1); 3 originated in acral locations. Tumor size ranged from 2.5 to 13 cm. Proportions of SEF-like and LGFMS-like areas varied considerably among tumors. All tumors that showed infiltrative growth and mitotic figures per 10 HPFs ranged from 0 to 18. Tumor necrosis was present in 1 case. Follow-up was available for 5 patients (11 to 321 mo), 2 of whom developed local recurrences, and 1 died of metastatic disease. The clinical behavior of these soft tissue sarcomas remains to be further delineated in larger series with extended follow-up; however, our limited clinical data indicate that they are potentially aggressive.", "doi": "10.1097/PAS.0000000000001423", "pmid": "31913156", "labels": {"Clinical Genomics Lund": "Service", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "00000478-202005000-00003"}], "notes": [], "created": "2020-12-02T03:53:53.417Z", "modified": "2024-01-16T13:48:42.553Z"}, {"entity": "publication", "iuid": "c37642986c1a4793b4f19cc918c4a9df", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c37642986c1a4793b4f19cc918c4a9df.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c37642986c1a4793b4f19cc918c4a9df"}}, "title": "Parentage and relatedness reconstruction in Pinus sylvestris using genotyping-by-sequencing.", "authors": [{"family": "Hall", "given": "David", "initials": "D"}, {"family": "Zhao", "given": "Wei", "initials": "W", "orcid": "0000-0001-9437-3198", "researcher": {"href": "https://publications.scilifelab.se/researcher/896aadb8e0dd4a82b93506003604209c.json"}}, {"family": "Wennstr\u00f6m", "given": "Ulfstand", "initials": "U"}, {"family": "Andersson Gull", "given": "Bengt", "initials": "B"}, {"family": "Wang", "given": "Xiao-Ru", "initials": "XR"}], "type": "journal article", "published": "2020-05-00", "journal": {"title": "Heredity (Edinb)", "issn": "1365-2540", "volume": "124", "issue": "5", "pages": "633-646", "issn-l": "0018-067X"}, "abstract": "Estimating kinship is fundamental for studies of evolution, conservation, and breeding. Genotyping-by-sequencing (GBS) and other restriction based genotyping methods have become widely applied in these applications in non-model organisms. However, sequencing errors, depth, and reproducibility between library preps could potentially hinder accurate genetic inferences. In this study, we tested different sets of parameters in data filtering, different reference populations and eight estimation methods to obtain a robust procedure for relatedness estimation in Scots pine (Pinus sylvestris L.). We used a seed orchard as our study system, where candidate parents are known and pedigree reconstruction can be compared with theoretical expectations. We found that relatedness estimates were lower than expected for all categories of kinship estimated if the proportion of shared SNPs was low. However, estimates reached expected values if loci showing an excess of heterozygotes were removed and genotyping error rates were considered. The genetic variance-covariance matrix (G-matrix) estimation, however, performed poorly in kinship estimation. The reduced relatedness estimates are likely due to false heterozygosity calls. We analyzed the mating structure in the seed orchard and identified a selfing rate of 3% (including crosses between clone mates) and external pollen contamination of 33.6%. Little genetic structure was observed in the sampled Scots pine natural populations, and the degree of inbreeding in the orchard seed crop is comparable to natural stands. We illustrate that under our optimized data processing procedure, relatedness, and genetic composition, including level of pollen contamination within a seed orchard crop, can be established consistently by different estimators.", "doi": "10.1038/s41437-020-0302-3", "pmid": "32123330", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41437-020-0302-3"}, {"db": "pmc", "key": "PMC7171117"}, {"db": "Dryad", "key": "10.5061/dryad.h44j0zpg5"}], "notes": [], "created": "2021-12-08T13:46:13.578Z", "modified": "2021-12-08T13:46:13.626Z"}, {"entity": "publication", "iuid": "bb997306e41d4015a6818367c73c9090", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bb997306e41d4015a6818367c73c9090.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bb997306e41d4015a6818367c73c9090"}}, "title": "Next-Generation Sequencing Reveals Differential Responses to Acute versus Long-Term Exposures to Graphene Oxide in Human Lung Cells.", "authors": [{"family": "Mukherjee", "given": "Sourav P", "initials": "SP"}, {"family": "Gupta", "given": "Govind", "initials": "G"}, {"family": "Kl\u00f6ditz", "given": "Katharina", "initials": "K"}, {"family": "Wang", "given": "Jun", "initials": "J"}, {"family": "Rodrigues", "given": "Artur Filipe", "initials": "AF"}, {"family": "Kostarelos", "given": "Kostas", "initials": "K"}, {"family": "Fadeel", "given": "Bengt", "initials": "B", "orcid": "0000-0001-5559-8482", "researcher": {"href": "https://publications.scilifelab.se/researcher/959b4accdbfe49158353b8cb12260d1b.json"}}], "type": "journal article", "published": "2020-05-00", "journal": {"title": "Small", "issn": "1613-6829", "volume": "16", "issue": "21", "pages": "e1907686", "issn-l": "1613-6810"}, "abstract": "Numerous studies have addressed the biological impact of graphene-based materials including graphene oxide (GO), yet few have focused on long-term effects. Here, RNA sequencing is utilized to unearth responses of human lung cells to GO. To this end, the BEAS-2B cell line derived from normal human bronchial epithelium is subjected to repeated, low-dose exposures of GO (1 or 5 \u00b5g mL-1 ) for 28 days or to the equivalent, cumulative amount of GO for 48 h. Then, samples are analyzed by using the NovaSeq 6000 sequencing system followed by pathway analysis and gene ontology enrichment analysis of the differentially expressed genes. Significant differences are seen between the low-dose, long-term exposures and the high-dose, short-term exposures. Hence, exposure to GO for 48 h results in mitochondrial dysfunction. In contrast, exposure to GO for 28 days is characterized by engagement of apoptosis pathways with downregulation of genes belonging to the inhibitor of apoptosis protein (IAP) family. Validation experiments confirm that long-term exposure to GO affects the apoptosis threshold in lung cells, accompanied by a loss of IAPs. These studies reveal the sensitivity of RNA-sequencing approaches and show that acute exposure to GO is not a good predictor of the long-term effects of GO.", "doi": "10.1002/smll.201907686", "pmid": "32227449", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service"}, "xrefs": [], "notes": [], "created": "2020-07-08T13:04:38.790Z", "modified": "2021-11-10T12:51:36.115Z"}, {"entity": "publication", "iuid": "0ea80926bb3240349dae2e9cb5fb3448", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0ea80926bb3240349dae2e9cb5fb3448.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0ea80926bb3240349dae2e9cb5fb3448"}}, "title": "Monitoring calcium-induced epidermal differentiation in vitro using multiphoton microscopy.", "authors": [{"family": "Malak", "given": "Monika", "initials": "M"}, {"family": "Grantham", "given": "Julie", "initials": "J"}, {"family": "Ericson", "given": "Marica B", "initials": "MB"}], "type": "journal article", "published": "2020-05-00", "journal": {"title": "J Biomed Opt", "issn": "1560-2281", "volume": "25", "issue": "7", "pages": "1-11", "issn-l": null}, "abstract": "Research in tissue engineering and in vitro organ formation has recently intensified. To assess tissue morphology, the method of choice today is restricted primarily to histology. Thus novel tools are required to enable noninvasive, and preferably label-free, three-dimensional imaging that is more compatible with futuristic organ-on-a-chip models.\n\nWe investigate the potential for using multiphoton microscopy (MPM) as a label-free in vitro approach to monitor calcium-induced epidermal differentiation.\n\nIn vitro epidermis was cultured at the air-liquid interface in varying calcium concentrations. Morphology and tissue architecture were investigated using MPM based on visualizing cellular autofluorescence.\n\nDistinct morphologies corresponding to epidermal differentiation were observed. In addition, Ca2 + -induced effects could be distinguished based on the architectural differences in stratification in the tissue cultures.\n\nOur study shows that MPM based on cellular autofluorescence enables visualization of Ca2 + -induced differentiation in epidermal skin models in vitro. The technique has potential to be further adapted as a noninvasive, label-free, and real-time tool to monitor tissue regeneration and organ formation in vitro.", "doi": "10.1117/1.JBO.25.7.071205", "pmid": "32388932", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7210787"}, {"db": "pii", "key": "JBO-190345SSRR"}], "notes": [], "created": "2023-02-16T08:08:00.526Z", "modified": "2023-02-16T08:08:00.558Z"}, {"entity": "publication", "iuid": "e9a65d41693e4874b05f362bedb21539", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e9a65d41693e4874b05f362bedb21539.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e9a65d41693e4874b05f362bedb21539"}}, "title": "In-depth plasma proteomics reveals increase in circulating PD-1 during anti-PD-1 immunotherapy in patients with metastatic cutaneous melanoma.", "authors": [{"family": "Baba\u010di\u0107", "given": "Haris", "initials": "H", "orcid": "0000-0003-0813-0005", "researcher": {"href": "https://publications.scilifelab.se/researcher/45a1c5d3d2d34a9e96d112877632784c.json"}}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J"}, {"family": "Pico de Coa\u00f1a", "given": "Yago", "initials": "Y"}, {"family": "Pernemalm", "given": "Maria", "initials": "M"}, {"family": "Eriksson", "given": "Hanna", "initials": "H"}], "type": "journal article", "published": "2020-05-00", "journal": {"title": "J Immunother Cancer", "issn": "2051-1426", "volume": "8", "issue": "1", "pages": "e000204", "issn-l": null}, "abstract": "Immune checkpoint inhibitors (ICIs) have significantly improved the outcome in metastatic cutaneous melanoma (CM). However, therapy response is limited to subgroups of patients and clinically useful predictive biomarkers are lacking.\n\nTo discover treatment-related systemic changes in plasma and potential biomarkers associated with treatment outcome, we analyzed serial plasma samples from 24 patients with metastatic CM, collected before and during ICI treatment, with mass-spectrometry-based global proteomics (high-resolution isoelectric focusing liquid chromatography-mass spectrometry (HiRIEF LC-MS/MS)) and targeted proteomics with proximity extension assays (PEAs). In addition, we analyzed plasma proteomes of 24 patients with metastatic CM treated with mitogen-activated protein kinase inhibitors (MAPKis), to pinpoint changes in protein plasma levels specific to the ICI treatment. To detect plasma proteins associated with treatment response, we performed stratified analyses in anti-programmed cell death protein 1 (anti-PD-1) responders and non-responders. In addition, we analyzed the association between protein plasma levels and progression-free survival (PFS) by Cox proportional hazards models.\n\nUnbiased HiRIEF LC-MS/MS-based proteomics showed plasma levels' alterations related to anti-PD-1 treatment in 80 out of 1160 quantified proteins. Circulating PD-1 had the highest increase during anti-PD-1 treatment (log2-FC=2.03, p=0.0008) and in anti-PD-1 responders (log2-FC=2.09, p=0.005), but did not change in the MAPKis cohort. Targeted, antibody-based proteomics by PEA confirmed this observation. Anti-PD-1 responders had an increase in plasma proteins involved in T-cell response, neutrophil degranulation, inflammation, cell adhesion, and immune suppression. Furthermore, we discovered new associations between plasma proteins (eg, interleukin 6, interleukin 10, proline-rich acidic protein 1, desmocollin 3, C-C motif chemokine ligands 2, 3 and 4, vascular endothelial growth factor A) and PFS, which may serve as predictive biomarkers.\n\nWe detected an increase in circulating PD-1 during anti-PD-1 treatment, as well as diverse immune plasma proteomic signatures in anti-PD-1 responders. This study demonstrates the potential of plasma proteomics as a liquid biopsy method and in discovery of putative predictive biomarkers for anti-PD-1 treatment in metastatic CM.", "doi": "10.1136/jitc-2019-000204", "pmid": "32457125", "labels": {"Bioinformatics Support, Infrastructure and Training": "Service", "Bioinformatics Support and Infrastructure": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pii", "key": "jitc-2019-000204"}, {"db": "pmc", "key": "PMC7253007"}], "notes": [], "created": "2021-08-13T11:12:42.966Z", "modified": "2021-11-10T12:51:37.325Z"}, {"entity": "publication", "iuid": "bab887d8bdcd4298b21a1edc1dca962e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bab887d8bdcd4298b21a1edc1dca962e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bab887d8bdcd4298b21a1edc1dca962e"}}, "title": "Genetic identification of cell types underlying brain complex traits yields insights into the etiology of Parkinson's disease.", "authors": [{"family": "Bryois", "given": "Julien", "initials": "J"}, {"family": "Skene", "given": "Nathan G", "initials": "NG"}, {"family": "Hansen", "given": "Thomas Folkmann", "initials": "TF", "orcid": "0000-0001-6703-7762", "researcher": {"href": "https://publications.scilifelab.se/researcher/56994131a2ef4278b802dc55c838d88a.json"}}, {"family": "Kogelman", "given": "Lisette J A", "initials": "LJA"}, {"family": "Watson", "given": "Hunna J", "initials": "HJ", "orcid": "0000-0001-8405-381X", "researcher": {"href": "https://publications.scilifelab.se/researcher/8fd919535931490ba39b80b794349c49.json"}}, {"family": "Liu", "given": "Zijing", "initials": "Z"}, {"family": "Eating Disorders Working Group of the Psychiatric Genomics Consortium", "given": "", "initials": ""}, {"family": "International Headache Genetics Consortium", "given": "", "initials": ""}, {"family": "23andMe Research Team", "given": "", "initials": ""}, {"family": "Brueggeman", "given": "Leo", "initials": "L"}, {"family": "Breen", "given": "Gerome", "initials": "G", "orcid": "0000-0003-2053-1792", "researcher": {"href": "https://publications.scilifelab.se/researcher/e25b495fde8d4e1d9f26779c2af6a541.json"}}, {"family": "Bulik", "given": "Cynthia M", "initials": "CM"}, {"family": "Arenas", "given": "Ernest", "initials": "E", "orcid": "0000-0003-0197-6577", "researcher": {"href": "https://publications.scilifelab.se/researcher/a3bb18ad1c4b4dae99b60ab0ae13e36a.json"}}, {"family": "Hjerling-Leffler", "given": "Jens", "initials": "J", "orcid": "0000-0002-4539-1776", "researcher": {"href": "https://publications.scilifelab.se/researcher/51675f0ff9aa47d89d6b2eb84a14820a.json"}}, {"family": "Sullivan", "given": "Patrick F", "initials": "PF", "orcid": "0000-0002-6619-873X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4d95de0b5ab14586980a6a13c8299346.json"}}], "type": "journal article", "published": "2020-05-00", "journal": {"title": "Nat. Genet.", "issn": "1546-1718", "issn-l": "1061-4036", "volume": "52", "issue": "5", "pages": "482-493"}, "abstract": "Genome-wide association studies have discovered hundreds of loci associated with complex brain disorders, but it remains unclear in which cell types these loci are active. Here we integrate genome-wide association study results with single-cell transcriptomic data from the entire mouse nervous system to systematically identify cell types underlying brain complex traits. We show that psychiatric disorders are predominantly associated with projecting excitatory and inhibitory neurons. Neurological diseases were associated with different cell types, which is consistent with other lines of evidence. Notably, Parkinson's disease was genetically associated not only with cholinergic and monoaminergic neurons (which include dopaminergic neurons) but also with enteric neurons and oligodendrocytes. Using post-mortem brain transcriptomic data, we confirmed alterations in these cells, even at the earliest stages of disease progression. Our study provides an important framework for understanding the cellular basis of complex brain maladies, and reveals an unexpected role of oligodendrocytes in Parkinson's disease.", "doi": "10.1038/s41588-020-0610-9", "pmid": "32341526", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41588-020-0610-9"}, {"db": "pmc", "key": "PMC7930801"}, {"db": "mid", "key": "NIHMS1672179"}], "notes": [], "created": "2020-05-06T12:23:56.414Z", "modified": "2024-01-16T13:48:42.561Z"}, {"entity": "publication", "iuid": "610723ef8cdd41789643686e1766ccc8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/610723ef8cdd41789643686e1766ccc8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/610723ef8cdd41789643686e1766ccc8"}}, "title": "Early growth response 1 regulates hematopoietic support and proliferation in human primary bone marrow stromal cells.", "authors": [{"family": "Li", "given": "Hongzhe", "initials": "H"}, {"family": "Lim", "given": "Hooi-Ching", "initials": "HC"}, {"family": "Zacharaki", "given": "Dimitra", "initials": "D"}, {"family": "Xian", "given": "Xiaojie", "initials": "X"}, {"family": "Kenswil", "given": "Keane J G", "initials": "KJG"}, {"family": "Br\u00e4unig", "given": "Sandro", "initials": "S"}, {"family": "Raaijmakers", "given": "Marc H G P", "initials": "MHGP"}, {"family": "Woods", "given": "Niels-Bjarne", "initials": "NB"}, {"family": "Hansson", "given": "Jenny", "initials": "J"}, {"family": "Scheding", "given": "Stefan", "initials": "S"}], "type": "journal article", "published": "2020-05-00", "journal": {"title": "Haematologica", "issn": "1592-8721", "volume": "105", "issue": "5", "pages": "1206-1215", "issn-l": "0390-6078"}, "abstract": "Human bone marrow stromal cells (BMSC) are key elements of the hematopoietic environment and they play a central role in bone and bone marrow physiology. However, how key stromal cell functions are regulated is largely unknown. We analyzed the role of the immediate early response transcription factor EGR1 as key stromal cell regulator and found that EGR1 was highly expressed in prospectively-isolated primary BMSC, down-regulated upon culture, and low in non-colony-forming CD45neg stromal cells. Furthermore, EGR1 expression was lower in proliferative regenerating adult and fetal primary cells compared to adult steady-state BMSC. Overexpression of EGR1 in stromal cells induced potent hematopoietic stroma support as indicated by an increased production of transplantable CD34+CD90+ hematopoietic stem cells in expansion co-cultures. The improvement in bone marrow stroma support function was mediated by increased expression of hematopoietic supporting genes, such as VCAM1 and CCL28 Furthermore, EGR1 overexpression markedly decreased stromal cell proliferation whereas EGR1 knockdown caused the opposite effects. These findings thus show that EGR1 is a key stromal transcription factor with a dual role in regulating proliferation and hematopoietic stroma support function that is controlling a genetic program to co-ordinate the specific functions of BMSC in their different biological contexts.", "doi": "10.3324/haematol.2019.216648", "pmid": "31371413", "labels": {"Clinical Genomics Lund": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "haematol.2019.216648"}, {"db": "pmc", "key": "PMC7193482"}], "notes": [], "created": "2019-12-13T15:10:31.698Z", "modified": "2021-11-10T12:51:38.450Z"}, {"entity": "publication", "iuid": "6ca2f2e474b740f98e9763440327cb37", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6ca2f2e474b740f98e9763440327cb37.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6ca2f2e474b740f98e9763440327cb37"}}, "title": "Deep sequencing of myxoinflammatory fibroblastic sarcoma.", "authors": [{"family": "Arbajian", "given": "Elsa", "initials": "E"}, {"family": "Hofvander", "given": "Jakob", "initials": "J"}, {"family": "Magnusson", "given": "Linda", "initials": "L"}, {"family": "Mertens", "given": "Fredrik", "initials": "F", "orcid": "0000-0002-6278-5232", "researcher": {"href": "https://publications.scilifelab.se/researcher/909230c16f7840a49798794167232e76.json"}}], "type": "journal article", "published": "2020-05-00", "journal": {"title": "Genes Chromosomes Cancer", "issn": "1098-2264", "volume": "59", "issue": "5", "pages": "309-317", "issn-l": "1045-2257"}, "abstract": "Myxoinflammatory fibroblastic sarcoma (MIFS) has recurrent genetic features in the form of a translocation t(1;10)(p22-31;q24-25), BRAF gene fusions, and/or an amplicon in 3p11-12 including the VGLL3 gene. The breakpoints on chromosomes 1 and 10 in the t(1;10) cluster in or near the TGFBR3 and OGA genes, respectively. We here used a combination of deep sequencing of the genome (WGS), captured sequences (Cap-seq), and transcriptome (RNA-seq) and genomic arrays to investigate the molecular outcome of the t(1;10) and the VGLL3 amplicon, as well as to assess the spectrum of other recurrent genomic features in MIFS. Apart from a ROBO1-BRAF chimera in a t(1;10)-negative MIFS-like tumor, no fusion gene was found at RNA-seq. This was in line with WGS and Cap-seq results, revealing variable breakpoints in chromosomes 1 and 10 and genomic breakpoints that should not yield functional fusion transcripts. The most common genomic rearrangements were breakpoints in or around the OGA, NPM3, and FGF8 genes in chromosome band 10q24, and loss of 1p11-p21 and 10q26-qter (all simultaneously present in 6/7 MIFS); a breakpoint in or near TGFBR3 in chromosome 1 was found in four of these tumors. Amplification and overexpression of VGLL3 was a consistent feature in MIFS and MIFS-like tumors with amplicons in 3p11-12. The significant molecular genetic outcome of the recurrent t(1;10) could be loss of genetic material from 1p and 10q. Other recurrent genomic imbalances in MIFS, such as homozygous loss of CDKN2A and 3p- and 13q-deletions, are shared with other sarcomas, suggesting overlapping pathogenetic pathways.", "doi": "10.1002/gcc.22832", "pmid": "31898851", "labels": {"Clinical Genomics Lund": "Service", "Clinical Genomics": "Service"}, "xrefs": [], "notes": [], "created": "2021-11-23T13:01:46.185Z", "modified": "2021-11-23T13:03:23.655Z"}, {"entity": "publication", "iuid": "142cd7c968884f7cb68eacee4c77c4b8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/142cd7c968884f7cb68eacee4c77c4b8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/142cd7c968884f7cb68eacee4c77c4b8"}}, "title": "Comprehensive chemical proteomics for target deconvolution of the redox active drug auranofin.", "authors": [{"family": "Saei", "given": "Amir Ata", "initials": "AA"}, {"family": "Gullberg", "given": "Hjalmar", "initials": "H"}, {"family": "Sabatier", "given": "Pierre", "initials": "P"}, {"family": "Beusch", "given": "Christian M", "initials": "CM"}, {"family": "Johansson", "given": "Katarina", "initials": "K"}, {"family": "Lundgren", "given": "Bo", "initials": "B"}, {"family": "Arvidsson", "given": "Per I", "initials": "PI", "orcid": "0000-0002-9453-6812", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae064b90b750457e80e974947f2dfc7a.json"}}, {"family": "Arn\u00e9r", "given": "Elias S J", "initials": "ESJ"}, {"family": "Zubarev", "given": "Roman A", "initials": "RA", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}], "type": "journal article", "published": "2020-05-00", "journal": {"title": "Redox Biol", "issn": "2213-2317", "volume": "32", "issue": null, "pages": "101491", "issn-l": null}, "abstract": "Chemical proteomics encompasses novel drug target deconvolution methods in which compound modification is not required. Herein we use Thermal Proteome Profiling, Functional Identification of Target by Expression Proteomics and multiplexed redox proteomics for deconvolution of auranofin targets to aid elucidation of its mechanisms of action. Auranofin (Ridaura\u00ae) was approved for treatment of rheumatoid arthritis in 1985. Because several clinical trials are currently ongoing to repurpose auranofin for cancer therapy, comprehensive characterization of its targets and effects in cancer cells is important. Together, our chemical proteomics tools confirmed thioredoxin reductase 1 (TXNRD1, EC:1.8.1.9) as a main auranofin target, with perturbation of oxidoreductase pathways as the top mechanism of drug action. Additional indirect targets included NFKB2 and CHORDC1. Our comprehensive data can be used as a proteomic signature resource for further analyses of the effects of auranofin. Here we also assessed the orthogonality and complementarity of different chemical proteomics methods that can furnish invaluable mechanistic information and thus the approach can facilitate drug discovery efforts in general.", "doi": "10.1016/j.redox.2020.101491", "pmid": "32199331", "labels": {"Drug Discovery and Development": null}, "xrefs": [{"db": "pii", "key": "S2213-2317(20)30243-3"}, {"db": "pmc", "key": "PMC7082630"}], "notes": [], "created": "2020-12-04T14:18:10.861Z", "modified": "2025-10-17T13:05:08.024Z"}, {"entity": "publication", "iuid": "3512e2bf962741998ecc07bef378e14b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3512e2bf962741998ecc07bef378e14b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3512e2bf962741998ecc07bef378e14b"}}, "title": "Analysis of DNA methylation patterns in the tumor immune microenvironment of metastatic melanoma.", "authors": [{"family": "Mitra", "given": "Shamik", "initials": "S", "orcid": "0000-0001-6995-0600", "researcher": {"href": "https://publications.scilifelab.se/researcher/b3b10a7bd10941d58ee17b74795931fd.json"}}, {"family": "Lauss", "given": "Martin", "initials": "M"}, {"family": "Cabrita", "given": "Rita", "initials": "R"}, {"family": "Choi", "given": "Jiyeon", "initials": "J"}, {"family": "Zhang", "given": "Tongwu", "initials": "T"}, {"family": "Isaksson", "given": "Karolin", "initials": "K"}, {"family": "Olsson", "given": "H\u00e5kan", "initials": "H"}, {"family": "Ingvar", "given": "Christian", "initials": "C"}, {"family": "Carneiro", "given": "Ana", "initials": "A"}, {"family": "Staaf", "given": "Johan", "initials": "J"}, {"family": "Ringn\u00e9r", "given": "Markus", "initials": "M"}, {"family": "Nielsen", "given": "Kari", "initials": "K"}, {"family": "Brown", "given": "Kevin M", "initials": "KM"}, {"family": "J\u00f6nsson", "given": "G\u00f6ran", "initials": "G", "orcid": "0000-0001-6865-0147", "researcher": {"href": "https://publications.scilifelab.se/researcher/0099af8e34f64a37a35392d32a0d357e.json"}}], "type": "journal article", "published": "2020-05-00", "journal": {"title": "Mol Oncol", "issn": "1878-0261", "volume": "14", "issue": "5", "pages": "933-950", "issn-l": "1574-7891"}, "abstract": "The presence of immune cells in the tumor microenvironment has been associated with response to immunotherapies across several cancer types, including melanoma. Despite its therapeutic relevance, characterization of the melanoma immune microenvironments remains insufficiently explored. To distinguish the immune microenvironment in a cohort of 180 metastatic melanoma clinical specimens, we developed a method using promoter CpG methylation of immune cell type-specific genes extracted from genome-wide methylation arrays. Unsupervised clustering identified three immune methylation clusters with varying levels of immune CpG methylation that are related to patient survival. Matching protein and gene expression data further corroborated the identified epigenetic characterization. Exploration of the possible immune exclusion mechanisms at play revealed likely dependency on MITF protein level and PTEN loss-of-function events for melanomas unresponsive to immunotherapies (immune-low). To understand whether melanoma tumors resemble other solid tumors in terms of immune methylation characteristics, we explored 15 different solid tumor cohorts from TCGA. Low-dimensional projection based on immune cell type-specific methylation revealed grouping of the solid tumors in line with melanoma immune methylation clusters rather than tumor types. Association of survival outcome with immune cell type-specific methylation differed across tumor and cell types. However, in melanomas immune cell type-specific methylation was associated with inferior patient survival. Exploration of the immune methylation patterns in a pan-cancer context suggested that specific immune microenvironments might occur across the cancer spectrum. Together, our findings underscore the existence of diverse immune microenvironments, which may be informative for future immunotherapeutic applications.", "doi": "10.1002/1878-0261.12663", "pmid": "32147909", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC7191190"}], "notes": [], "created": "2020-05-07T10:58:12.836Z", "modified": "2024-01-16T13:48:42.568Z"}, {"entity": "publication", "iuid": "ccaa6b6173b94902bf80b8a831521a1a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ccaa6b6173b94902bf80b8a831521a1a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ccaa6b6173b94902bf80b8a831521a1a"}}, "title": "A molecular mechanism explaining albuminuria in kidney disease.", "authors": [{"family": "Butt", "given": "Linus", "initials": "L"}, {"family": "Unnersj\u00f6-Jess", "given": "David", "initials": "D", "orcid": "0000-0002-4162-0973", "researcher": {"href": "https://publications.scilifelab.se/researcher/9d475fc7a52a46e4abe984191c5b5b5f.json"}}, {"family": "H\u00f6hne", "given": "Martin", "initials": "M", "orcid": "0000-0001-8698-5389", "researcher": {"href": "https://publications.scilifelab.se/researcher/4d3ddd0be3164d0d9f483d9c0755c499.json"}}, {"family": "Edwards", "given": "Aurelie", "initials": "A"}, {"family": "Binz-Lotter", "given": "Julia", "initials": "J", "orcid": "0000-0003-4678-0703", "researcher": {"href": "https://publications.scilifelab.se/researcher/1a5b26232abe4fd6b4df6c1cadc56f1f.json"}}, {"family": "Reilly", "given": "Dervla", "initials": "D"}, {"family": "Hahnfeldt", "given": "Robert", "initials": "R", "orcid": "0000-0001-7997-3216", "researcher": {"href": "https://publications.scilifelab.se/researcher/e54b718629e742cf966ea885a9120ef5.json"}}, {"family": "Ziegler", "given": "Vera", "initials": "V"}, {"family": "Fremter", "given": "Katharina", "initials": "K"}, {"family": "Rinschen", "given": "Markus M", "initials": "MM", "orcid": "0000-0002-9252-1342", "researcher": {"href": "https://publications.scilifelab.se/researcher/8b6fcd4a72d346cf865aed8b10f49a2d.json"}}, {"family": "Helmst\u00e4dter", "given": "Martin", "initials": "M"}, {"family": "Ebert", "given": "Lena K", "initials": "LK"}, {"family": "Castrop", "given": "Hayo", "initials": "H"}, {"family": "Hackl", "given": "Matthias J", "initials": "MJ"}, {"family": "Walz", "given": "Gerd", "initials": "G", "orcid": "0000-0002-4950-9946", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd9545e1cff9413e9c2b76920aa53b3e.json"}}, {"family": "Brinkkoetter", "given": "Paul T", "initials": "PT"}, {"family": "Liebau", "given": "Max C", "initials": "MC", "orcid": "0000-0003-0494-9080", "researcher": {"href": "https://publications.scilifelab.se/researcher/678310bc460e4921bb67c6c6670f24d0.json"}}, {"family": "Tory", "given": "K\u00e1lm\u00e1n", "initials": "K", "orcid": "0000-0002-0316-6212", "researcher": {"href": "https://publications.scilifelab.se/researcher/774101da128248578efdccb22b38475b.json"}}, {"family": "Hoyer", "given": "Peter F", "initials": "PF", "orcid": "0000-0002-9132-0282", "researcher": {"href": "https://publications.scilifelab.se/researcher/b12d4092ef9347c1ba1e982e535b9819.json"}}, {"family": "Beck", "given": "Bodo B", "initials": "BB"}, {"family": "Brismar", "given": "Hjalmar", "initials": "H", "orcid": "0000-0003-0578-4003", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ec23336e2ef4e298f340876f1136dce.json"}}, {"family": "Blom", "given": "Hans", "initials": "H", "orcid": "0000-0002-5584-9170", "researcher": {"href": "https://publications.scilifelab.se/researcher/3ce356a74dc84e0ea6af85397f11d869.json"}}, {"family": "Schermer", "given": "Bernhard", "initials": "B", "orcid": "0000-0002-5194-9000", "researcher": {"href": "https://publications.scilifelab.se/researcher/e6ccc28a64e9402fa608fb657d874080.json"}}, {"family": "Benzing", "given": "Thomas", "initials": "T", "orcid": "0000-0003-0512-1066", "researcher": {"href": "https://publications.scilifelab.se/researcher/9c18d7e8857e426b9e6f38b06cca6992.json"}}], "type": "journal article", "published": "2020-05-00", "journal": {"title": "Nat Metab", "issn": "2522-5812", "volume": "2", "issue": "5", "pages": "461-474", "issn-l": "2522-5812"}, "abstract": "Mammalian kidneys constantly filter large amounts of liquid, with almost complete retention of albumin and other macromolecules in the plasma. Breakdown of the three-layered renal filtration barrier results in loss of albumin into urine (albuminuria) across the wall of small renal capillaries, and is a leading cause of chronic kidney disease. However, exactly how the renal filter works and why its permeability is altered in kidney diseases is poorly understood. Here we show that the permeability of the renal filter is modulated through compression of the capillary wall. We collect morphometric data prior to and after onset of albuminuria in a mouse model equivalent to a human genetic disease affecting the renal filtration barrier. Combining quantitative analyses with mathematical modelling, we demonstrate that morphological alterations of the glomerular filtration barrier lead to reduced compressive forces that counteract filtration pressure, thereby resulting in capillary dilatation, and ultimately albuminuria. Our results reveal distinct functions of the different layers of the filtration barrier and expand the molecular understanding of defective renal filtration in chronic kidney disease.", "doi": "10.1038/s42255-020-0204-y", "pmid": "32694662", "labels": {"Integrated Microscopy Technologies Stockholm": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s42255-020-0204-y"}], "notes": [], "created": "2020-05-26T07:14:25.600Z", "modified": "2021-11-10T12:51:42.052Z"}, {"entity": "publication", "iuid": "9f5f8533edb94e54a14be784d8fa0566", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9f5f8533edb94e54a14be784d8fa0566.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9f5f8533edb94e54a14be784d8fa0566"}}, "title": "Interactive proteogenomic exploration of response to Fusarium head blight in oat varieties with different resistance.", "authors": [{"family": "Willforss", "given": "J", "initials": "J"}, {"family": "Leonova", "given": "S", "initials": "S"}, {"family": "Tillander", "given": "J", "initials": "J"}, {"family": "Andreasson", "given": "E", "initials": "E"}, {"family": "Marttila", "given": "S", "initials": "S"}, {"family": "Olsson", "given": "O", "initials": "O"}, {"family": "Chawade", "given": "A", "initials": "A"}, {"family": "Levander", "given": "F", "initials": "F"}], "type": "journal article", "published": "2020-04-30", "journal": {"title": "J Proteomics", "issn": "1876-7737", "volume": "218", "pages": "103688", "issn-l": "1874-3919"}, "abstract": "Fusarium species are cereal pathogens that cause the Fusarium Head Blight (FHB) disease. FHB can reduce yield, cause mycotoxin accumulation in the grain and reduce germination efficiency of the harvested seeds. Understanding the biochemical interactions between the host plants and the pathogen is crucial for controlling the disease and for the development of cultivars with improved tolerance to FHB. Here, we studied morphological and proteomic differences between the susceptible oat variety Belinda and the more resistant variety Argamak using variety-specific transcriptome assemblies as references. Measurements of deoxynivalenol toxin levels confirmed the partial resistance in Argamak and the susceptibility in Belinda. To jointly investigate the proteomics- and sequence data, we developed an RShiny-based interface for interactive exploration of the dataset using univariate and multivariate statistics. When applying this interface to the dataset, quantitative protein differences between Belinda and Argamak were detected, and eighteen peptides were found uniquely in Argamak during infection, among them several lipoxygenases. Such proteins can be developed as markers for Fusarium resistance breeding. In conclusion, this study provides the first proteogenomic insight on molecular Fusarium-oat interactions at both morphological and molecular levels and the data are openly available through an interactive interface for further inspection. SIGNIFICANCE: Fusarium head blight causes widespread damage to crops, and chronic and acute toxicity to human and livestock due to the accumulation of toxins during infection. In the present study, two oat varieties with differing resistance were challenged with Fusarium to understand the disease better, and studied both at morphological and molecular levels, identifying proteins which could play a role in the defense mechanism. Furthermore, a proteogenomics approach allows joint profiling of expression and sequence level differences to identify potentially functionally differing mutations. Here such analysis is made openly available through an interactive interface which allows other scientists to draw further findings from the data. This study may both serve as a basis for understanding oat disease response and developing breeding markers for Fusarium resistant oat and future proteogenomic studies using the interactive approach described.", "doi": "10.1016/j.jprot.2020.103688", "pmid": "32061841", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S1874-3919(20)30056-7"}], "notes": [], "created": "2021-12-02T14:04:07.686Z", "modified": "2021-12-02T14:04:07.699Z"}, {"entity": "publication", "iuid": "916daac68b0c42c4ae5cdac53d6c2682", "links": {"self": {"href": "https://publications.scilifelab.se/publication/916daac68b0c42c4ae5cdac53d6c2682.json"}, "display": {"href": "https://publications.scilifelab.se/publication/916daac68b0c42c4ae5cdac53d6c2682"}}, "title": "Interactions of the Lysosomotropic Detergent O-Methyl-Serine Dodecylamide Hydrochloride (MSDH) with Lipid Bilayer Membranes-Implications for Cell Toxicity.", "authors": [{"family": "Villamil Giraldo", "given": "Ana-Maria", "initials": "AM"}, {"family": "Eriksson", "given": "Ida", "initials": "I"}, {"family": "Wennmalm", "given": "Stefan", "initials": "S"}, {"family": "Fyrner", "given": "Timmy", "initials": "T", "orcid": "0000-0003-2119-9883", "researcher": {"href": "https://publications.scilifelab.se/researcher/9e979061c9c141cdb8d03ff13144ce71.json"}}, {"family": "Ederth", "given": "Thomas", "initials": "T", "orcid": "0000-0002-1639-5735", "researcher": {"href": "https://publications.scilifelab.se/researcher/4d18d4a955f941b89b2880b9203a01b6.json"}}, {"family": "\u00d6llinger", "given": "Karin", "initials": "K"}], "type": "journal article", "published": "2020-04-29", "journal": {"title": "Int J Mol Sci", "issn": "1422-0067", "volume": "21", "issue": "9", "pages": "3136", "issn-l": null}, "abstract": "O-methyl-serine dodecylamine hydrochloride (MSDH) is a detergent that accumulates selectively in lysosomes, a so-called lysosomotropic detergent, with unexpected chemical properties. At physiological pH, it spontaneously forms vesicles, which disassemble into small aggregates (probably micelles) below pH 6.4. In this study, we characterize the interaction between MSDH and liposomes at different pH and correlate the findings to toxicity in human fibroblasts. We find that the effect of MSDH on lipid membranes is highly pH-dependent. At neutral pH, the partitioning of MSDH into the liposome membrane is immediate and causes the leakage of small fluorophores, unless the ratio between MSDH and lipids is kept low. At pH 5, the partitioning of MSDH into the membrane is kinetically impeded since MSDH is charged and a high ratio between MSDH and the lipids is required to permeabilize the membrane. When transferred to cell culture conditions, the ratio between MSDH and plasma membrane lipids must therefore be low, at physiological pH, to maintain plasma membrane integrity. Transmission electron microscopy suggests that MSDH vesicles are taken up by endocytosis. As the pH of the endosomal compartment progressively drops, MSDH vesicles disassemble, leading to a high concentration of increasingly charged MSDH in small aggregates inside the lysosomes. At sufficiently high MSDH concentrations, the lysosome is permeabilized, the proteolytic content released to the cytosol and apoptotic cell death is induced.", "doi": "10.3390/ijms21093136", "pmid": "32365555", "labels": {"Integrated Microscopy Technologies Stockholm": "Collaborative"}, "xrefs": [{"db": "pii", "key": "ijms21093136"}, {"db": "pmc", "key": "PMC7247706"}], "notes": [], "created": "2020-06-29T15:48:48.517Z", "modified": "2021-11-10T12:51:43.179Z"}, {"entity": "publication", "iuid": "cb4e4c3ac9fc472eaf821f490243290d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cb4e4c3ac9fc472eaf821f490243290d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cb4e4c3ac9fc472eaf821f490243290d"}}, "title": "Fungal Diversity in the Phyllosphere of Pinus heldreichii H. Christ\u2014An Endemic and High-Altitude Pine of the Mediterranean Region", "authors": [{"family": "Lazarevi\u0107", "given": "Jelena", "initials": "J"}, {"family": "Menkis", "given": "Audrius", "initials": "A", "orcid": "0000-0002-6545-8907", "researcher": {"href": "https://publications.scilifelab.se/researcher/7d4d16d281344b9f9cf2c3c27fb40f06.json"}}], "type": "journal-article", "published": "2020-04-28", "journal": {"title": "Diversity", "issn": "1424-2818", "volume": "12", "issue": "5", "pages": "172", "issn-l": "1424-2818"}, "abstract": null, "doi": "10.3390/d12050172", "pmid": null, "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service"}, "xrefs": [], "notes": [], "created": "2020-05-26T18:02:09.045Z", "modified": "2021-11-10T12:39:49.198Z"}, {"entity": "publication", "iuid": "363b739d24b643d29fe3d400f87f1af9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/363b739d24b643d29fe3d400f87f1af9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/363b739d24b643d29fe3d400f87f1af9"}}, "title": "DNA methylation and copy number variation profiling of T-cell lymphoblastic leukemia and lymphoma.", "authors": [{"family": "Haider", "given": "Zahra", "initials": "Z", "orcid": "0000-0002-0759-3932", "researcher": {"href": "https://publications.scilifelab.se/researcher/4084e066170543e699dd116c8e7c05df.json"}}, {"family": "Landfors", "given": "Mattias", "initials": "M"}, {"family": "Golovleva", "given": "Irina", "initials": "I", "orcid": "0000-0001-8741-0616", "researcher": {"href": "https://publications.scilifelab.se/researcher/b12b365ee27e430c9d17c5c07c762e28.json"}}, {"family": "Erlanson", "given": "Martin", "initials": "M"}, {"family": "Schmiegelow", "given": "Kjeld", "initials": "K"}, {"family": "Fl\u00e6gstad", "given": "Trond", "initials": "T"}, {"family": "Kanerva", "given": "Jukka", "initials": "J"}, {"family": "Nor\u00e9n-Nystr\u00f6m", "given": "Ulrika", "initials": "U"}, {"family": "Hultdin", "given": "Magnus", "initials": "M"}, {"family": "Degerman", "given": "Sofie", "initials": "S", "orcid": "0000-0002-2783-0712", "researcher": {"href": "https://publications.scilifelab.se/researcher/8611162e883645f59195c4221199967f.json"}}], "type": "journal article", "published": "2020-04-28", "journal": {"title": "Blood Cancer J", "issn": "2044-5385", "issn-l": "2044-5385", "volume": "10", "issue": "4", "pages": "45"}, "abstract": "Despite having common overlapping immunophenotypic and morphological features, T-cell lymphoblastic leukemia (T-ALL) and lymphoma (T-LBL) have distinct clinical manifestations, which may represent separate diseases. We investigated and compared the epigenetic and genetic landscape of adult and pediatric T-ALL (n = 77) and T-LBL (n = 15) patient samples by high-resolution genome-wide DNA methylation and Copy Number Variation (CNV) BeadChip arrays. DNA methylation profiling identified the presence of CpG island methylator phenotype (CIMP) subgroups within both pediatric and adult T-LBL and T-ALL. An epigenetic signature of 128 differentially methylated CpG sites was identified, that clustered T-LBL and T-ALL separately. The most significant differentially methylated gene loci included the SGCE/PEG10 shared promoter region, previously implicated in lymphoid malignancies. CNV analysis confirmed overlapping recurrent aberrations between T-ALL and T-LBL, including 9p21.3 (CDKN2A/CDKN2B) deletions. A significantly higher frequency of chromosome 13q14.2 deletions was identified in T-LBL samples (36% in T-LBL vs. 0% in T-ALL). This deletion, encompassing the RB1, MIR15A and MIR16-1 gene loci, has been reported as a recurrent deletion in B-cell malignancies. Our study reveals epigenetic and genetic markers that can distinguish between T-LBL and T-ALL, and deepen the understanding of the biology underlying the diverse disease localization.", "doi": "10.1038/s41408-020-0310-9", "pmid": "32345961", "labels": {"Clinical Genomics Ume\u00e5": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41408-020-0310-9"}, {"db": "pmc", "key": "PMC7188684"}], "notes": [], "created": "2021-06-18T12:10:04.144Z", "modified": "2021-12-08T14:16:53.085Z"}, {"entity": "publication", "iuid": "f724f6c819fe4b4fb8005fa9c3dc68f7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f724f6c819fe4b4fb8005fa9c3dc68f7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f724f6c819fe4b4fb8005fa9c3dc68f7"}}, "title": "Biodiversity between sand grains: Meiofauna composition across southern and western Sweden assessed by metabarcoding.", "authors": [{"family": "Atherton", "given": "Sarah", "initials": "S", "orcid": "0000-0003-2847-2192", "researcher": {"href": "https://publications.scilifelab.se/researcher/6582e2e560474080a7d89240a3d43edd.json"}}, {"family": "Jondelius", "given": "Ulf", "initials": "U", "orcid": "0000-0003-2847-2192", "researcher": {"href": "https://publications.scilifelab.se/researcher/6582e2e560474080a7d89240a3d43edd.json"}}], "type": "journal article", "published": "2020-04-27", "journal": {"title": "Biodivers Data J", "issn": "1314-2828", "volume": "8", "issue": null, "pages": "e51813", "issn-l": null}, "abstract": "The meiofauna is an important part of the marine ecosystem, but its composition and distribution patterns are relatively unexplored. Here we assessed the biodiversity and community structure of meiofauna from five locations on the Swedish western and southern coasts using a high-throughput DNA sequencing (metabarcoding) approach. The mitochondrial cytochrome oxidase 1 (COI) mini-barcode and nuclear 18S small ribosomal subunit (18S) V1-V2 region were amplified and sequenced using Illumina MiSeq technology. Our analyses revealed a higher number of species than previously found in other areas: thirteen samples comprising 6.5 dm3 sediment revealed 708 COI and 1,639 18S metazoan OTUs. Across all sites, the majority of the metazoan biodiversity was assigned to Arthropoda, Nematoda and Platyhelminthes. Alpha and beta diversity measurements showed that community composition differed significantly amongst sites. OTUs initially assigned to Acoela, Gastrotricha and the two Platyhelminthes sub-groups Macrostomorpha and Rhabdocoela were further investigated and assigned to species using a phylogeny-based taxonomy approach. Our results demonstrate that there is great potential for discovery of new meiofauna species even in some of the most extensively studied locations.", "doi": "10.3897/BDJ.8.e51813", "pmid": "32390756", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "51813"}, {"db": "pmc", "key": "PMC7198628"}], "notes": [], "created": "2020-07-08T13:04:39.455Z", "modified": "2024-01-16T13:48:42.575Z"}, {"entity": "publication", "iuid": "918f7d4f8dfe45a1b19ca927caac47c8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/918f7d4f8dfe45a1b19ca927caac47c8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/918f7d4f8dfe45a1b19ca927caac47c8"}}, "title": "Mending Fences: Na,K-ATPase signaling via Ca2+ in the maintenance of epithelium integrity.", "authors": [{"family": "Aperia", "given": "Anita", "initials": "A"}, {"family": "Brismar", "given": "Hjalmar", "initials": "H", "orcid": "0000-0003-0578-4003", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ec23336e2ef4e298f340876f1136dce.json"}}, {"family": "Uhl\u00e9n", "given": "Per", "initials": "P"}], "type": "journal article", "published": "2020-04-26", "journal": {"title": "Cell Calcium", "issn": "0143-4160", "volume": "88", "issue": null, "pages": "102210", "issn-l": null}, "abstract": "Na,K-ATPase is a ubiquitous multifunctional protein that acts both as an ion pump and as a signal transducer. The signaling function is activated by ouabain in non-toxic concentrations. In epithelial cells the ouabain-bound Na,K-ATPase connects with the inositol 1,4,5-trisphosphate receptor via a short linear motif to activate low frequency Ca2+ oscillations. Within a couple of minutes this ouabain mediated signal has resulted in phosphorylation or dephosphorylation of 2580 phospho-sites. Proteins that control cell proliferation and cell adhesion and calmodulin regulated proteins are enriched among the ouabain phosphor-regulated proteins. The inositol 1,4,5-trisphosphate receptor and the stromal interaction molecule, which are both essential for the initiation of Ca2+ oscillations, belong to the ouabain phosphor-regulated proteins. Downstream effects of the ouabain-evoked Ca2+ signal in epithelial cells include interference with the intrinsic mitochondrial apoptotic process and stimulation of embryonic growth processes. The dual function of Na,K-ATPase as an ion pump and a signal transducer is now well established and evaluation of the physiological and pathophysiological consequences of this universal signal emerges as an urgent topic for future studies.", "doi": "10.1016/j.ceca.2020.102210", "pmid": "32380435", "labels": {"Integrated Microscopy Technologies Stockholm": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0143-4160(20)30052-X"}], "notes": [], "created": "2020-12-10T21:27:56.923Z", "modified": "2021-11-10T12:51:47.830Z"}, {"entity": "publication", "iuid": "863700044a8a4486b41dff7546900424", "links": {"self": {"href": "https://publications.scilifelab.se/publication/863700044a8a4486b41dff7546900424.json"}, "display": {"href": "https://publications.scilifelab.se/publication/863700044a8a4486b41dff7546900424"}}, "title": "Low occurrence of extended-spectrum cephalosporinase producing Enterobacteriaceae and no detection of methicillin-resistant coagulase-positive staphylococci in healthy dogs in Sweden.", "authors": [{"family": "B\u00f6rjesson", "given": "Stefan", "initials": "S"}, {"family": "Gunnarsson", "given": "Lotta", "initials": "L"}, {"family": "Land\u00e9n", "given": "Annica", "initials": "A"}, {"family": "Gr\u00f6nlund", "given": "Ulrika", "initials": "U"}], "type": "journal article", "published": "2020-04-25", "journal": {"title": "Acta Vet. Scand.", "issn": "1751-0147", "volume": "62", "issue": "1", "pages": "18", "issn-l": "0044-605X"}, "abstract": "Sweden has a long tradition of monitoring occurrence of antibiotic resistant bacteria in both animals and humans, but there currently is no organised and harmonized monitoring on carriage of Enterobacteriaceae producing extended-spectrum beta-lactamase (ESBL), plasmid-mediated AmpC beta-lactamase (pAmpC), or methicillin-resistant coagulase positive staphylococci e.g. methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus pseudintermedius (MRSP) in dogs. The aim of the current study was therefore to determine the prevalence of ESBL/pAmpC producing Enterobacteriaceae and methicillin-resistant coagulase positive staphylococci in healthy dogs in Sweden, and to phenotypically and genotypically characterize any identified isolates. It was shown that 0.9% (95% confident interval 0.3-2.7%) of the dogs (n = 325) carried multi-resistant ESBL-producing Escherichia coli, but that no methicillin-resistant coagulase positive staphylococci could be detected. In conclusion, the occurrence of multi-drug resistant bacteria remains rare among healthy dogs in Sweden. In addition, the ESBL-producing E. coli identified showed genetic characteristics related to those reported from humans.", "doi": "10.1186/s13028-020-00516-4", "pmid": "32334616", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s13028-020-00516-4"}, {"db": "pmc", "key": "PMC7183698"}], "notes": [], "created": "2020-11-22T14:29:46.977Z", "modified": "2021-11-10T12:51:48.975Z"}, {"entity": "publication", "iuid": "1ae27c3fa358492db50c421a6b3861b2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1ae27c3fa358492db50c421a6b3861b2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1ae27c3fa358492db50c421a6b3861b2"}}, "title": "Optimization of Tetrahydroindazoles as Inhibitors of Human Dihydroorotate Dehydrogenase and Evaluation of Their Activity and In Vitro Metabolic Stability.", "authors": [{"family": "Popova", "given": "Gergana", "initials": "G", "orcid": "0000-0001-9804-4041", "researcher": {"href": "https://publications.scilifelab.se/researcher/8c02b2503754423eb0af5cf07e6c64b5.json"}}, {"family": "Ladds", "given": "Marcus J G W", "initials": "MJGW"}, {"family": "Johansson", "given": "Lars", "initials": "L"}, {"family": "Saleh", "given": "Aljona", "initials": "A"}, {"family": "Larsson", "given": "Johanna", "initials": "J"}, {"family": "Sandberg", "given": "Lars", "initials": "L"}, {"family": "Sahlberg", "given": "Sara H\u00e4ggblad", "initials": "SH"}, {"family": "Qian", "given": "Weixing", "initials": "W"}, {"family": "Gullberg", "given": "Hjalmar", "initials": "H"}, {"family": "Garg", "given": "Neeraj", "initials": "N"}, {"family": "Gustavsson", "given": "Anna-Lena", "initials": "A"}, {"family": "Haraldsson", "given": "Martin", "initials": "M"}, {"family": "Lane", "given": "David", "initials": "D"}, {"family": "Yngve", "given": "Ulrika", "initials": "U"}, {"family": "Lain", "given": "Sonia", "initials": "S"}], "type": "journal article", "published": "2020-04-23", "journal": {"title": "J. Med. Chem.", "issn": "1520-4804", "issn-l": "0022-2623", "volume": "63", "issue": "8", "pages": "3915-3934"}, "abstract": "Human dihydroorotate dehydrogenase (DHODH), an enzyme in the de novo pyrimidine synthesis pathway, is a target for the treatment of rheumatoid arthritis and multiple sclerosis and is re-emerging as an attractive target for cancer therapy. Here we describe the optimization of recently identified tetrahydroindazoles (HZ) as DHODH inhibitors. Several of the HZ analogues synthesized in this study are highly potent inhibitors of DHODH in an enzymatic assay, while also inhibiting cancer cell growth and viability and activating p53-dependent transcription factor activity in a reporter cell assay. Furthermore, we demonstrate the specificity of the compounds toward the de novo pyrimidine synthesis pathway through supplementation with an excess of uridine. We also show that induction of the DNA damage marker \u03b3-H2AX after DHODH inhibition is preventable by cotreatment with the pan-caspase inhibitor Z-VAD-FMK. Additional solubility and in vitro metabolic stability profiling revealed compound 51 as a favorable candidate for preclinical efficacy studies.", "doi": "10.1021/acs.jmedchem.9b01658", "pmid": "32212728", "labels": {"Chemical Biology Consortium Sweden": "Collaborative", "Drug Discovery and Development": "Service"}, "xrefs": [], "notes": [], "created": "2020-04-20T10:13:37.088Z", "modified": "2025-10-17T13:05:08.036Z"}, {"entity": "publication", "iuid": "c5e1b42d52a0441e9779b05de930430f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c5e1b42d52a0441e9779b05de930430f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c5e1b42d52a0441e9779b05de930430f"}}, "title": "Trade-off between somatic and germline repair in a vertebrate supports the expensive germ line hypothesis.", "authors": [{"family": "Chen", "given": "Hwei-Yen", "initials": "HY"}, {"family": "Jolly", "given": "Cecile", "initials": "C"}, {"family": "Bublys", "given": "Kasparas", "initials": "K"}, {"family": "Marcu", "given": "Daniel", "initials": "D", "orcid": "0000-0002-2151-5850", "researcher": {"href": "https://publications.scilifelab.se/researcher/38a0bc0f57fc405bb806bcd8a19b9bea.json"}}, {"family": "Immler", "given": "Simone", "initials": "S"}], "type": "journal article", "published": "2020-04-21", "journal": {"title": "Proc. Natl. Acad. Sci. U.S.A.", "issn": "1091-6490", "volume": "117", "issue": "16", "pages": "8973-8979", "issn-l": "0027-8424"}, "abstract": "The disposable soma theory is a central tenet of the biology of aging where germline immortality comes at the cost of an aging soma [T. B. L. Kirkwood, Nature 270, 301-304 (1977); T. B. L. Kirkwood, Proc. R. Soc. Lond. B Biol. Sci. 205, 531-546 (1979); T. B. L. Kirkwood, S. N. Austad, Nature 408, 233-238 (2000)]. Limited resources and a possible trade-off between the repair and maintenance of the germ cells and growth and maintenance of the soma may explain the deterioration of the soma over time. Here we show that germline removal allows accelerated somatic healing under stress. We tested \"the expensive germ line\" hypothesis by generating germline-free zebrafish Danio rerio and testing the effect of the presence and absence of the germ line on somatic repair under benign and stressful conditions. We exposed male fish to sublethal low-dose ionizing radiation, a genotoxic stress affecting the soma and the germ line, and tested how fast the soma recovered following partial fin ablation. We found that somatic recovery from ablation occurred substantially faster in irradiated germline-free fish than in the control germline-carrying fish where somatic recovery was stunned. The germ line did show signs of postirradiation recovery in germline-carrying fish in several traits related to offspring number and fitness. These results support the theoretical conjecture that germline maintenance is costly and directly trades off with somatic maintenance.", "doi": "10.1073/pnas.1918205117", "pmid": "32245815", "labels": {"Genome Engineering Zebrafish": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "1918205117"}, {"db": "pmc", "key": "PMC7183174"}, {"db": "Dryad", "key": "10.5061/dryad.mkkwh70w8"}], "notes": [], "created": "2020-05-22T07:49:04.262Z", "modified": "2024-01-16T13:48:42.582Z"}, {"entity": "publication", "iuid": "1e994159b3374183b4c8d606199303e3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1e994159b3374183b4c8d606199303e3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1e994159b3374183b4c8d606199303e3"}}, "title": "Studies of Emission Processes of Polymer Additives into Water Using Quartz Crystal Microbalance-A Case Study on Organophosphate Esters.", "authors": [{"family": "Xiao", "given": "Linhong", "initials": "L", "orcid": "0000-0002-1780-705X", "researcher": {"href": "https://publications.scilifelab.se/researcher/5d935960d1cc4028b1eacad9dcb0483d.json"}}, {"family": "Zheng", "given": "Ziye", "initials": "Z", "orcid": "0000-0002-7898-341X", "researcher": {"href": "https://publications.scilifelab.se/researcher/66f7c8ba6f1d4e138fdf84618b25f30f.json"}}, {"family": "Irgum", "given": "Knut", "initials": "K"}, {"family": "Andersson", "given": "Patrik L", "initials": "PL", "orcid": "0000-0002-2088-6756", "researcher": {"href": "https://publications.scilifelab.se/researcher/a8828c70fd7a4ce583bb9e53bfb677ea.json"}}], "type": "journal article", "published": "2020-04-21", "journal": {"title": "Environ. Sci. Technol.", "issn": "1520-5851", "volume": "54", "issue": "8", "pages": "4876-4885", "issn-l": "0013-936X"}, "abstract": "Plastic materials contain various additives, which can be released during the entire lifespan of plastics and pose a threat to the environment and human health. Despite our knowledge on leakage of additives from products, accurate and rapid approaches to study emission kinetics are largely lacking, in particular, methodologies that can provide in-depth understanding of polymer/additive interactions. Here, we report on a novel approach using quartz crystal microbalance (QCM) to measure emissions of additives to water from polymer films spin-coated on quartz crystals. The methodology, being accurate and reproducible with a standard error of \u00b12.4%, was applied to a range of organophosphate esters (OPEs) and polymers with varying physicochemical properties. The release of most OPEs reached an apparent steady-state within 10 h. The release curves for the studied OPEs could be fitted using a Weibull model, which shows that the release is a two-phase process with an initial fast phase driven by partitioning of OPEs readily available at or close to the polymer film surface, and a slower phase dominated by diffusion in the polymer. The kinetics of the first emission phase was mainly correlated with the hydrophobicity of the OPEs, whereas the diffusion phase was weakly correlated with molecular size. The developed QCM-based method for assessing and studying release of organic chemicals from a polymeric matrix is well suited for rapid screening of additives in efforts to identify more sustainable replacement polymer additives with lower emission potential.", "doi": "10.1021/acs.est.9b07607", "pmid": "32186175", "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7884016"}], "notes": [], "created": "2020-11-24T20:27:47.355Z", "modified": "2025-10-17T13:03:56.977Z"}, {"entity": "publication", "iuid": "183a39b655614a3faef837da3a14521b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/183a39b655614a3faef837da3a14521b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/183a39b655614a3faef837da3a14521b"}}, "title": "Solution Conformations Explain the Chameleonic Behaviour of Macrocyclic Drugs.", "authors": [{"family": "Danelius", "given": "Emma", "initials": "E", "orcid": "0000-0002-7322-9661", "researcher": {"href": "https://publications.scilifelab.se/researcher/738da5a280d04d3b9b1ced257b9ddb7f.json"}}, {"family": "Poongavanam", "given": "Vasanthanathan", "initials": "V", "orcid": "0000-0002-8880-9247", "researcher": {"href": "https://publications.scilifelab.se/researcher/d037f230665c490dada0a50ecc8c106f.json"}}, {"family": "Peintner", "given": "Stefan", "initials": "S", "orcid": "0000-0001-9882-2018", "researcher": {"href": "https://publications.scilifelab.se/researcher/0583434982c84bd69f313f713744f5ed.json"}}, {"family": "Wieske", "given": "Lianne H E", "initials": "LHE", "orcid": "0000-0003-4617-7605", "researcher": {"href": "https://publications.scilifelab.se/researcher/9ee9a8547a194235a4d32170996b53e9.json"}}, {"family": "Erd\u00e9lyi", "given": "M\u00e1t\u00e9", "initials": "M", "orcid": "0000-0003-0359-5970", "researcher": {"href": "https://publications.scilifelab.se/researcher/f772b571449e417ca6fda2eee361a0c3.json"}}, {"family": "Kihlberg", "given": "Jan", "initials": "J", "orcid": "0000-0002-4205-6040", "researcher": {"href": "https://publications.scilifelab.se/researcher/f9805d4f39cc48f79a6e6ba076917021.json"}}], "type": "journal article", "published": "2020-04-21", "journal": {"title": "Chemistry", "issn": "1521-3765", "volume": "26", "issue": "23", "pages": "5231-5244", "issn-l": "0947-6539"}, "abstract": "It has been hypothesised that drugs in the chemical space \"beyond the rule of 5\" (bRo5) must behave as molecular chameleons to combine otherwise conflicting properties, including aqueous solubility, cell permeability and target binding. Evidence for this has, however, been limited to the cyclic peptide cyclosporine A. Herein, we show that the non-peptidic and macrocyclic drugs roxithromycin, telithromycin and spiramycin behave as molecular chameleons, with rifampicin showing a less pronounced behaviour. In particular roxithromycin, telithromycin and spiramycin display a marked, yet limited flexibility and populate significantly less polar and more compact conformational ensembles in an apolar than in a polar environment. In addition to balancing of membrane permeability and aqueous solubility, this flexibility also allows binding to targets that vary in structure between species. The drugs' passive cell permeability correlates to their 3D polar surface area and corroborate two theoretical models for permeability, developed for cyclic peptides. We conclude that molecular chameleonicity should be incorporated in the design of orally administered drugs in the bRo5 space.", "doi": "10.1002/chem.201905599", "pmid": "32027758", "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [], "notes": [], "created": "2020-12-11T09:13:45.140Z", "modified": "2025-10-17T13:03:56.989Z"}, {"entity": "publication", "iuid": "4317205fc07d449db7735d0732d85a4c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4317205fc07d449db7735d0732d85a4c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4317205fc07d449db7735d0732d85a4c"}}, "title": "Molecular profiling of driver events in metastatic uveal melanoma.", "authors": [{"family": "Karlsson", "given": "Joakim", "initials": "J", "orcid": "0000-0001-6332-4043", "researcher": {"href": "https://publications.scilifelab.se/researcher/6190c1a8a7d54cd6807f120e8748cfcd.json"}}, {"family": "Nilsson", "given": "Lisa M", "initials": "LM"}, {"family": "Mitra", "given": "Suman", "initials": "S"}, {"family": "Als\u00e9n", "given": "Samuel", "initials": "S"}, {"family": "Shelke", "given": "Ganesh Vilas", "initials": "GV", "orcid": "0000-0001-5883-8082", "researcher": {"href": "https://publications.scilifelab.se/researcher/beeaee610fe341d79fa92f2f4f9a9683.json"}}, {"family": "Sah", "given": "Vasu R", "initials": "VR"}, {"family": "Forsberg", "given": "Elin M V", "initials": "EMV", "orcid": "0000-0002-4196-3060", "researcher": {"href": "https://publications.scilifelab.se/researcher/5e6342bc14ba426bbf61704b4873377a.json"}}, {"family": "Stierner", "given": "Ulrika", "initials": "U"}, {"family": "All-Eriksson", "given": "Charlotta", "initials": "C"}, {"family": "Einarsdottir", "given": "Berglind", "initials": "B"}, {"family": "Jespersen", "given": "Henrik", "initials": "H", "orcid": "0000-0002-6543-5369", "researcher": {"href": "https://publications.scilifelab.se/researcher/d220a3bcbfea44228722a123b25ec1b2.json"}}, {"family": "Ny", "given": "Lars", "initials": "L"}, {"family": "Lindn\u00e9r", "given": "Per", "initials": "P"}, {"family": "Larsson", "given": "Erik", "initials": "E"}, {"family": "Olofsson Bagge", "given": "Roger", "initials": "R", "orcid": "0000-0001-5795-0355", "researcher": {"href": "https://publications.scilifelab.se/researcher/e1f8016d5e64418ca71f230e64e415ba.json"}}, {"family": "Nilsson", "given": "Jonas A", "initials": "JA", "orcid": "0000-0003-0346-6837", "researcher": {"href": "https://publications.scilifelab.se/researcher/27f0581f25124e98b0bd0eef8c3f3331.json"}}], "type": "journal article", "published": "2020-04-20", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "11", "issue": "1", "pages": "1894", "issn-l": "2041-1723"}, "abstract": "Metastatic uveal melanoma is less well understood than its primary counterpart, has a distinct biology compared to skin melanoma, and lacks effective treatments. Here we genomically profile metastatic tumors and infiltrating lymphocytes. BAP1 alterations are overrepresented and found in 29/32 of cases. Reintroducing a functional BAP1 allele into a deficient patient-derived cell line, reveals a broad shift towards a transcriptomic subtype previously associated with better prognosis of the primary disease. One outlier tumor has a high mutational burden associated with UV-damage. CDKN2A deletions also occur, which are rarely present in primaries. A focused knockdown screen is used to investigate overexpressed genes associated withcopy number gains. Tumor-infiltrating lymphocytes are in several cases found tumor-reactive, but expression of the immune checkpoint receptors TIM-3, TIGIT and LAG3 is also abundant. This study represents the largest whole-genome analysis of uveal melanoma to date, and presents an updated view of the metastatic disease.", "doi": "10.1038/s41467-020-15606-0", "pmid": "32313009", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-15606-0"}, {"db": "pmc", "key": "PMC7171146"}], "notes": [], "created": "2020-07-08T13:04:38.039Z", "modified": "2024-01-16T13:48:42.590Z"}, {"entity": "publication", "iuid": "b1e92191e1894e02ae64098f4f082a33", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b1e92191e1894e02ae64098f4f082a33.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b1e92191e1894e02ae64098f4f082a33"}}, "title": "Long-term stability of partial nitritation-anammox for treatment of municipal wastewater in a moving bed biofilm reactor pilot system.", "authors": [{"family": "Gustavsson", "given": "David J I", "initials": "DJI"}, {"family": "Suarez", "given": "Carolina", "initials": "C"}, {"family": "Wil\u00e9n", "given": "Britt-Marie", "initials": "BM"}, {"family": "Hermansson", "given": "Malte", "initials": "M"}, {"family": "Persson", "given": "Frank", "initials": "F"}], "type": "journal article", "published": "2020-04-20", "journal": {"title": "Sci. Total Environ.", "issn": "1879-1026", "volume": "714", "pages": "136342", "issn-l": "0048-9697"}, "abstract": "Nitrogen removal from the mainstream of municipal wastewater with partial nitritation-anammox (PNA) would be highly beneficial with regard to the uses of energy and organic carbon. However, the challenges of process instability, low nitrogen removal rates (NRR) and unwanted aerobic nitrite oxidation need to be solved to reach large-scale implementation. Here, we have operated pilot-scale moving bed biofilm reactors (MBBRs) for mainstream treatment, together with sidestream treatment of sludge liquor from anaerobic digestors, for over 900 days to investigate process stability, reactor performance and microbial community structure at realistic conditions. The MBBR biofilm contained stable and high relative abundances of anammox bacteria (10-32%) consisting of two major Brocadia sp. populations, and several populations of aerobic ammonia-oxidising bacteria (AOB) within Nitrosomonas sp. (0.2-3.1%), as assessed by 16S rDNA amplicon sequencing. In addition, nitrite-oxidising bacteria (NOB) consisting of Nitrospira sp. (0.4-0.8%) and Nitrotoga sp. (up to 0.4%) were present. Nitrogen was removed at a peak rate of 0.66 g N m-2 d-1 (0.13 kg N m-3 d-1) with a nitrate production over ammonium consumption of 15% by the NOB, at operation with continuous aeration at 15 \u00b0C. However, during most periods with continuous aeration, the NRR was lower (\u2248 0.45 g N m-2 d-1), with larger relative nitrate production (\u224840%), presumably due to problems to maintain stable residual ammonium concentrations during wet-weather mainstream flows. Changing reactor operation to intermittent aeration decreased the NRR but did not help in suppressing the NOB. The study shows that with MBBRs, stable mainstream PNA can be attained at realistic NRR, but with need for post-treatment of nitrate, since effective NOB suppression was hard to achieve.", "doi": "10.1016/j.scitotenv.2019.136342", "pmid": "31982771", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S0048-9697(19)36338-7"}], "notes": [], "created": "2023-02-16T08:07:06.862Z", "modified": "2023-02-16T08:07:06.874Z"}, {"entity": "publication", "iuid": "e62dab54473a4923903e72399e97dbdd", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e62dab54473a4923903e72399e97dbdd.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e62dab54473a4923903e72399e97dbdd"}}, "title": "Effect of Cobalt, Nickel, and Selenium/Tungsten Deficiency on Mesophilic Anaerobic Digestion of Chemically Defined Soluble Organic Compounds.", "authors": [{"family": "\u0160afari\u010d", "given": "Luka", "initials": "L", "orcid": "0000-0003-3274-0372", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a6e23745266454996cd0a93d9ffedac.json"}}, {"family": "Yekta", "given": "Sepehr Shakeri", "initials": "SS"}, {"family": "Svensson", "given": "Bo H", "initials": "BH"}, {"family": "Schn\u00fcrer", "given": "Anna", "initials": "A", "orcid": "0000-0003-0038-553X", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f81992bc8ed48318f8197fc8caabb4f.json"}}, {"family": "Bastviken", "given": "David", "initials": "D"}, {"family": "Bj\u00f6rn", "given": "Annika", "initials": "A"}], "type": "journal article", "published": "2020-04-20", "journal": {"title": "Microorganisms", "issn": "2076-2607", "volume": "8", "issue": "4", "pages": "598", "issn-l": "2076-2607"}, "abstract": "Trace elements (TEs) are vital for anaerobic digestion (AD), due to their role as cofactors in many key enzymes. The aim of this study was to evaluate the effects of specific TE deficiencies on mixed microbial communities during AD of soluble polymer-free substrates, thus focusing on AD after hydrolysis. Three mesophilic (37 \u00b0C) continuous stirred-tank biogas reactors were depleted either of Co, Ni, or a combination of Se and W, respectively, by discontinuing their supplementation. Ni and Se/W depletion led to changes in methane kinetics, linked to progressive volatile fatty acid (VFA) accumulation, eventually resulting in process failure. No significant changes occurred in the Co-depleted reactor, indicating that the amount of Co present in the substrate in absence of supplementation was sufficient to maintain process stability. Archaeal communities remained fairly stable independent of TE concentrations, while bacterial communities gradually changed with VFA accumulation in Ni- and Se-/W-depleted reactors. Despite this, the communities remained relatively similar between these two reactors, suggesting that the major shifts in composition likely occurred due to the accumulating VFAs. Overall, the results indicate that Ni and Se/W depletion primarily lead to slower metabolic activities of methanogenic archaea and their syntrophic partners, which then has a ripple effect throughout the microbial community due to a gradual accumulation of intermediate fermentation products.", "doi": "10.3390/microorganisms8040598", "pmid": "32326100", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "microorganisms8040598"}, {"db": "pmc", "key": "PMC7232481"}], "notes": [], "created": "2020-12-08T23:46:05.594Z", "modified": "2021-11-10T12:51:56.324Z"}, {"entity": "publication", "iuid": "ac4a845becd2473db2a0a012a4b9ebf2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ac4a845becd2473db2a0a012a4b9ebf2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ac4a845becd2473db2a0a012a4b9ebf2"}}, "title": "Fungi and Oomycetes in the Irrigation Water of Forest Nurseries", "authors": [{"family": "Mar\u010diulynas", "given": "Adas", "initials": "A"}, {"family": "Mar\u010diulynien\u0117", "given": "Diana", "initials": "D"}, {"family": "Lynikien\u0117", "given": "J\u016brat\u0117", "initials": "J"}, {"family": "Gedminas", "given": "Art\u016bras", "initials": "A"}, {"family": "Vai\u010diukyn\u0117", "given": "Migl\u0117", "initials": "M"}, {"family": "Menkis", "given": "Audrius", "initials": "A", "orcid": "0000-0002-6545-8907", "researcher": {"href": "https://publications.scilifelab.se/researcher/7d4d16d281344b9f9cf2c3c27fb40f06.json"}}], "type": "journal-article", "published": "2020-04-18", "journal": {"title": "Forests", "issn": "1999-4907", "volume": "11", "issue": "4", "pages": "459", "issn-l": "1999-4907"}, "abstract": null, "doi": "10.3390/f11040459", "pmid": null, "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service"}, "xrefs": [], "notes": [], "created": "2020-05-26T18:00:04.078Z", "modified": "2021-11-10T12:40:02.562Z"}, {"entity": "publication", "iuid": "3f9f66ea1370489190a392a79ce14ec8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3f9f66ea1370489190a392a79ce14ec8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3f9f66ea1370489190a392a79ce14ec8"}}, "title": "Rapid Biophysical Characterization and NMR Spectroscopy Structural Analysis of Small Proteins from Bacteria and Archaea.", "authors": [{"family": "Kubatova", "given": "Nina", "initials": "N"}, {"family": "Pyper", "given": "Dennis J", "initials": "DJ"}, {"family": "Jonker", "given": "Hendrik R A", "initials": "HRA"}, {"family": "Saxena", "given": "Krishna", "initials": "K"}, {"family": "Remmel", "given": "Laura", "initials": "L"}, {"family": "Richter", "given": "Christian", "initials": "C"}, {"family": "Brantl", "given": "Sabine", "initials": "S"}, {"family": "Evguenieva-Hackenberg", "given": "Elena", "initials": "E"}, {"family": "Hess", "given": "Wolfgang R", "initials": "WR"}, {"family": "Klug", "given": "Gabriele", "initials": "G"}, {"family": "Marchfelder", "given": "Anita", "initials": "A"}, {"family": "Soppa", "given": "J\u00f6rg", "initials": "J"}, {"family": "Streit", "given": "Wolfgang", "initials": "W"}, {"family": "Mayzel", "given": "Maxim", "initials": "M"}, {"family": "Orekhov", "given": "Vladislav Y", "initials": "VY"}, {"family": "Fuxreiter", "given": "Monika", "initials": "M"}, {"family": "Schmitz", "given": "Ruth A", "initials": "RA"}, {"family": "Schwalbe", "given": "Harald", "initials": "H", "orcid": "0000-0001-5693-7909", "researcher": {"href": "https://publications.scilifelab.se/researcher/56f923d2276148398bc85652f2b2a401.json"}}], "type": "journal article", "published": "2020-04-17", "journal": {"title": "ChemBioChem", "issn": "1439-7633", "volume": "21", "issue": "8", "pages": "1178-1187", "issn-l": "1439-4227"}, "abstract": "Proteins encoded by small open reading frames (sORFs) have a widespread occurrence in diverse microorganisms and can be of high functional importance. However, due to annotation biases and their technically challenging direct detection, these small proteins have been overlooked for a long time and were only recently rediscovered. The currently rapidly growing number of such proteins requires efficient methods to investigate their structure-function relationship. Herein, a method is presented for fast determination of the conformational properties of small proteins. Their small size makes them perfectly amenable for solution-state NMR spectroscopy. NMR spectroscopy can provide detailed information about their conformational states (folded, partially folded, and unstructured). In the context of the priority program on small proteins funded by the German research foundation (SPP2002), 27 small proteins from 9 different bacterial and archaeal organisms have been investigated. It is found that most of these small proteins are unstructured or partially folded. Bioinformatics tools predict that some of these unstructured proteins can potentially fold upon complex formation. A protocol for fast NMR spectroscopy structure elucidation is described for the small proteins that adopt a persistently folded structure by implementation of new NMR technologies, including automated resonance assignment and nonuniform sampling in combination with targeted acquisition.", "doi": "10.1002/cbic.201900677", "pmid": "31705614", "labels": {"Swedish NMR Centre": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC7217052"}], "notes": [], "created": "2020-01-07T11:43:11.424Z", "modified": "2025-10-17T13:03:57.000Z"}, {"entity": "publication", "iuid": "b44914598864495388f1d615d5e95c2b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b44914598864495388f1d615d5e95c2b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b44914598864495388f1d615d5e95c2b"}}, "title": "Genome-Scale Metabolic Modeling of Glioblastoma Reveals Promising Targets for Drug Development.", "authors": [{"family": "Larsson", "given": "Ida", "initials": "I"}, {"family": "Uhl\u00e9n", "given": "Mathias", "initials": "M", "orcid": "0000-0002-4858-8056", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff81da3cb0cf4262873b993a1b06798c.json"}}, {"family": "Zhang", "given": "Cheng", "initials": "C"}, {"family": "Mardinoglu", "given": "Adil", "initials": "A"}], "type": "journal article", "published": "2020-04-17", "journal": {"title": "Front Genet", "issn": "1664-8021", "volume": "11", "issue": null, "pages": "381", "issn-l": "1664-8021"}, "abstract": "Glioblastoma (GBM) is an aggressive type of brain cancer with a poor prognosis for affected patients. The current line of treatment only gives the patients a survival time of on average 15 months. In this work, we use genome-scale metabolic models (GEMs) together with other systems biology tools to examine the global transcriptomics-data of GBM-patients obtained from The Cancer Genome Atlas (TCGA). We reveal the molecular mechanisms underlying GBM and identify potential therapeutic targets for effective treatment of patients. The work presented consists of two main parts. The first part stratifies the patients into two groups, high and low survival, and compares their gene expression. The second part uses GBM and healthy brain tissue GEMs to simulate gene knockout in a GBM cell model to find potential therapeutic targets and predict their side effect in healthy brain tissue. We (1) find that genes upregulated in the patients with low survival are linked to various stages of the glioma invasion process, and (2) identify five essential genes for GBM, whose inhibition is non-toxic to healthy brain tissue, therefore promising to investigate further as therapeutic targets.", "doi": "10.3389/fgene.2020.00381", "pmid": "32362913", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7181968"}], "notes": [], "created": "2020-07-08T13:04:35.735Z", "modified": "2024-01-16T13:48:42.598Z"}, {"entity": "publication", "iuid": "cd9171508710494ba8bad2c1d95b8651", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cd9171508710494ba8bad2c1d95b8651.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cd9171508710494ba8bad2c1d95b8651"}}, "title": "Whole-genome genotyping and resequencing reveal the association of a deletion in the complex interferon alpha gene cluster with hypothyroidism in dogs.", "authors": [{"family": "Bianchi", "given": "Matteo", "initials": "M", "orcid": "0000-0003-3394-6495", "researcher": {"href": "https://publications.scilifelab.se/researcher/d645ef0e04a245f0ac9e7d7498b2bd69.json"}}, {"family": "Rafati", "given": "Nima", "initials": "N"}, {"family": "Karlsson", "given": "\u00c5sa", "initials": "\u00c5"}, {"family": "Mur\u00e9n", "given": "Eva", "initials": "E"}, {"family": "Rubin", "given": "Carl-Johan", "initials": "CJ"}, {"family": "Sundberg", "given": "Katarina", "initials": "K"}, {"family": "Andersson", "given": "G\u00f6ran", "initials": "G"}, {"family": "K\u00e4mpe", "given": "Olle", "initials": "O"}, {"family": "Hedhammar", "given": "\u00c5ke", "initials": "\u00c5"}, {"family": "Lindblad-Toh", "given": "Kerstin", "initials": "K", "orcid": "0000-0001-8338-0253", "researcher": {"href": "https://publications.scilifelab.se/researcher/e0063145f7d6476f80ab42f94833f4cf.json"}}, {"family": "Rosengren Pielberg", "given": "Gerli", "initials": "G"}], "type": "journal article", "published": "2020-04-16", "journal": {"title": "BMC Genomics", "issn": "1471-2164", "volume": "21", "issue": "1", "pages": "307", "issn-l": "1471-2164"}, "abstract": "Hypothyroidism is a common complex endocrinopathy that typically has an autoimmune etiology, and it affects both humans and dogs. Genetic and environmental factors are both known to play important roles in the disease development. In this study, we sought to identify the genetic risk factors potentially involved in the susceptibility to the disease in the high-risk Giant Schnauzer dog breed.\n\nBy employing genome-wide association followed by fine-mapping (top variant p-value = 5.7 \u00d7 10- 6), integrated with whole-genome resequencing and copy number variation analysis, we detected a ~ 8.9 kbp deletion strongly associated (p-value = 0.0001) with protection against development of hypothyroidism. The deletion is located between two predicted Interferon alpha (IFNA) genes and it may eliminate functional elements potentially involved in the transcriptional regulation of these genes. Remarkably, type I IFNs have been extensively associated to human autoimmune hypothyroidism and general autoimmunity. Nonetheless, the extreme genomic complexity of the associated region on CFA11 warrants further long-read sequencing and annotation efforts in order to ascribe functions to the identified deletion and to characterize the canine IFNA gene cluster in more detail.\n\nOur results expand the current knowledge on genetic determinants of canine hypothyroidism by revealing a significant link with the human counterpart disease, potentially translating into better diagnostic tools across species, and may contribute to improved canine breeding strategies.", "doi": "10.1186/s12864-020-6700-3", "pmid": "32299354", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12864-020-6700-3"}, {"db": "pmc", "key": "PMC7160888"}], "notes": [], "created": "2020-07-08T13:04:54.893Z", "modified": "2024-01-16T13:48:42.606Z"}, {"entity": "publication", "iuid": "b330828d9ccb481c88ca0ae89faaa9b1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b330828d9ccb481c88ca0ae89faaa9b1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b330828d9ccb481c88ca0ae89faaa9b1"}}, "title": "Capsid Structure of a Marine Algal Virus of the Order Picornavirales.", "authors": [{"family": "Munke", "given": "Anna", "initials": "A", "orcid": "0000-0002-5510-2245", "researcher": {"href": "https://publications.scilifelab.se/researcher/6fd6d8030171420190aa65f3eb1ac4bd.json"}}, {"family": "Kimura", "given": "Kei", "initials": "K"}, {"family": "Tomaru", "given": "Yuji", "initials": "Y", "orcid": "0000-0002-8164-6991", "researcher": {"href": "https://publications.scilifelab.se/researcher/85835893ee10481aafee34223ece859e.json"}}, {"family": "Okamoto", "given": "Kenta", "initials": "K", "orcid": "0000-0002-4858-1196", "researcher": {"href": "https://publications.scilifelab.se/researcher/9302e76f16a04afdbb72f00c805bffa4.json"}}], "type": "journal article", "published": "2020-04-16", "journal": {"title": "J. Virol.", "issn": "1098-5514", "volume": "94", "issue": "9", "pages": null, "issn-l": "0022-538X"}, "abstract": "The order Picornavirales includes viruses that infect different kinds of eukaryotes and that share similar properties. The capsid proteins (CPs) of viruses in the order that infect unicellular organisms, such as algae, presumably possess certain characteristics that have changed little over the course of evolution, and thus these viruses may resemble the Picornavirales ancestor in some respects. Herein, we present the capsid structure of Chaetoceros tenuissimus RNA virus type II (CtenRNAV-II) determined using cryo-electron microscopy at a resolution of 3.1 \u00c5, the first alga virus belonging to the family Marnaviridae of the order Picornavirales A structural comparison to related invertebrate and vertebrate viruses revealed a unique surface loop of the major CP VP1 that had not been observed previously, and further, revealed that another VP1 loop obscures the so-called canyon, which is a host-receptor binding site for many of the mammalian Picornavirales viruses. VP2 has an N-terminal tail, which has previously been reported as a primordial feature of Picornavirales viruses. The above-mentioned and other critical structural features provide new insights on three long-standing theories about Picornavirales: (i) the canyon hypothesis, (ii) the primordial VP2 domain swap, and (iii) the hypothesis that alga Picornavirales viruses could share characteristics with the Picornavirales ancestor.IMPORTANCE Identifying the acquired structural traits in virus capsids is important for elucidating what functions are essential among viruses that infect different hosts. The Picornavirales viruses infect a broad spectrum of hosts, ranging from unicellular algae to insects and mammals and include many human pathogens. Those viruses that infect unicellular protists, such as algae, are likely to have undergone fewer structural changes during the course of evolution compared to those viruses that infect multicellular eukaryotes and thus still share some characteristics with the Picornavirales ancestor. This article describes the first atomic capsid structure of an alga Marnavirus, CtenRNAV-II. A comparison to capsid structures of the related invertebrate and vertebrate viruses identified a number of structural traits that have been functionally acquired or lost during the course of evolution. These observations provide new insights on past theories on the viability and evolution of Picornavirales viruses.", "doi": "10.1128/JVI.01855-19", "pmid": "32024776", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pii", "key": "JVI.01855-19"}, {"db": "pmc", "key": "PMC7163153"}], "notes": [], "created": "2020-05-07T09:32:06.291Z", "modified": "2023-12-04T10:14:40.858Z"}, {"entity": "publication", "iuid": "65eed8901d6d42af899e7c58758820da", "links": {"self": {"href": "https://publications.scilifelab.se/publication/65eed8901d6d42af899e7c58758820da.json"}, "display": {"href": "https://publications.scilifelab.se/publication/65eed8901d6d42af899e7c58758820da"}}, "title": "The ELIXIR Core Data Resources: fundamental infrastructure for the life sciences.", "authors": [{"family": "Drysdale", "given": "Rachel", "initials": "R", "orcid": "0000-0003-3037-0216", "researcher": {"href": "https://publications.scilifelab.se/researcher/33a39d1bd31a47fa8b97d18159cc8011.json"}}, {"family": "Cook", "given": "Charles E", "initials": "CE", "orcid": "0000-0002-4145-8048", "researcher": {"href": "https://publications.scilifelab.se/researcher/ecc9ef8d51fc4157a3ec05a1b867b299.json"}}, {"family": "Petryszak", "given": "Robert", "initials": "R", "orcid": "0000-0001-6333-2182", "researcher": {"href": "https://publications.scilifelab.se/researcher/e28a71d259a848139d6f78b8d3d084bc.json"}}, {"family": "Baillie-Gerritsen", "given": "Vivienne", "initials": "V", "orcid": "0000-0003-3759-9494", "researcher": {"href": "https://publications.scilifelab.se/researcher/8741677b9d3345f98bcccb55f7a9113b.json"}}, {"family": "Barlow", "given": "Mary", "initials": "M", "orcid": "0000-0003-3072-6972", "researcher": {"href": "https://publications.scilifelab.se/researcher/80530fb41f3d4e918cee1d2d4bc9cb22.json"}}, {"family": "Gasteiger", "given": "Elisabeth", "initials": "E", "orcid": "0000-0003-1829-162X", "researcher": {"href": "https://publications.scilifelab.se/researcher/1868e360a5d64ef28128abb2bb505fe0.json"}}, {"family": "Gruhl", "given": "Franziska", "initials": "F", "orcid": "0000-0002-2613-7211", "researcher": {"href": "https://publications.scilifelab.se/researcher/d962777efcff4e71a54715350e7e6b32.json"}}, {"family": "Haas", "given": "J\u00fcrgen", "initials": "J", "orcid": "0000-0002-3255-7773", "researcher": {"href": "https://publications.scilifelab.se/researcher/2df0a1f228cc4f75948d69e2071c6d53.json"}}, {"family": "Lanfear", "given": "Jerry", "initials": "J", "orcid": "0000-0002-8007-5568", "researcher": {"href": "https://publications.scilifelab.se/researcher/9fbbf24c85954f5c9a30c462324b5879.json"}}, {"family": "Lopez", "given": "Rodrigo", "initials": "R", "orcid": "0000-0003-1256-7306", "researcher": {"href": "https://publications.scilifelab.se/researcher/812bdcf43316497fa12c464c9144bf21.json"}}, {"family": "Redaschi", "given": "Nicole", "initials": "N", "orcid": "0000-0001-8890-2268", "researcher": {"href": "https://publications.scilifelab.se/researcher/1014fb1d54b74e83ad65bab619cd472c.json"}}, {"family": "Stockinger", "given": "Heinz", "initials": "H", "orcid": "0000-0003-4666-7719", "researcher": {"href": "https://publications.scilifelab.se/researcher/92e85405298241c09fc5c4ea2d4858c0.json"}}, {"family": "Teixeira", "given": "Daniel", "initials": "D", "orcid": "0000-0003-2110-4725", "researcher": {"href": "https://publications.scilifelab.se/researcher/2af9d42eb6894cda9078f239f062ebd6.json"}}, {"family": "Venkatesan", "given": "Aravind", "initials": "A", "orcid": "0000-0003-4019-1940", "researcher": {"href": "https://publications.scilifelab.se/researcher/fb91f1527afa492c99fbbe75e9579a8a.json"}}, {"family": "Elixir Core Data Resource Forum", "given": "", "initials": ""}, {"family": "Blomberg", "given": "Niklas", "initials": "N", "orcid": "0000-0003-4155-5910", "researcher": {"href": "https://publications.scilifelab.se/researcher/d559b48215aa4a198d9613b0128e8eb4.json"}}, {"family": "Durinx", "given": "Christine", "initials": "C", "orcid": "0000-0003-4237-8899", "researcher": {"href": "https://publications.scilifelab.se/researcher/9691f63a3ac94222914f6e4df747c591.json"}}, {"family": "McEntyre", "given": "Johanna", "initials": "J", "orcid": "0000-0002-1611-6935", "researcher": {"href": "https://publications.scilifelab.se/researcher/3ccdaedf5c884aea8d4b8d99a9caf67f.json"}}], "type": "journal article", "published": "2020-04-15", "journal": {"title": "Bioinformatics", "issn": "1367-4811", "issn-l": "1367-4803", "volume": "36", "issue": "8", "pages": "2636-2642"}, "abstract": "Supplementary data are available at Bioinformatics online.", "doi": "10.1093/bioinformatics/btz959", "pmid": "31950984", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "5709034"}, {"db": "pmc", "key": "PMC7446027"}], "notes": [], "created": "2020-01-09T14:47:16.425Z", "modified": "2021-11-10T12:52:02.149Z"}, {"entity": "publication", "iuid": "0501e4e6d44c4a8c947ef756d0262288", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0501e4e6d44c4a8c947ef756d0262288.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0501e4e6d44c4a8c947ef756d0262288"}}, "title": "Increased burden of ultra-rare structural variants localizing to boundaries of topologically associated domains in schizophrenia.", "authors": [{"family": "Halvorsen", "given": "Matthew", "initials": "M"}, {"family": "Huh", "given": "Ruth", "initials": "R"}, {"family": "Oskolkov", "given": "Nikolay", "initials": "N", "orcid": "0000-0001-5326-8893", "researcher": {"href": "https://publications.scilifelab.se/researcher/1a556bc2e89c457fb1e45cfcd7b567e9.json"}}, {"family": "Wen", "given": "Jia", "initials": "J", "orcid": "0000-0003-3273-7704", "researcher": {"href": "https://publications.scilifelab.se/researcher/872570fb0f94464d988fd5b2d3a8b7e7.json"}}, {"family": "Netotea", "given": "Sergiu", "initials": "S"}, {"family": "Giusti-Rodriguez", "given": "Paola", "initials": "P", "orcid": "0000-0002-1921-1305", "researcher": {"href": "https://publications.scilifelab.se/researcher/e6594f03c6c344d69b08234fd751ab23.json"}}, {"family": "Karlsson", "given": "Robert", "initials": "R", "orcid": "0000-0002-8949-2587", "researcher": {"href": "https://publications.scilifelab.se/researcher/9df14bf33f3342408d624caa70d45b7c.json"}}, {"family": "Bryois", "given": "Julien", "initials": "J"}, {"family": "Nystedt", "given": "Bj\u00f6rn", "initials": "B", "orcid": "0000-0001-7809-7664", "researcher": {"href": "https://publications.scilifelab.se/researcher/f0af5a168baa4b00a6fab8d3447ebfb4.json"}}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "K\u00e4hler", "given": "Anna K", "initials": "AK"}, {"family": "Ancalade", "given": "NaEshia", "initials": "N"}, {"family": "Farrell", "given": "Martilias", "initials": "M", "orcid": "0000-0002-9520-6209", "researcher": {"href": "https://publications.scilifelab.se/researcher/20be04f56c474537ad8fa07cb17241cf.json"}}, {"family": "Crowley", "given": "James J", "initials": "JJ"}, {"family": "Li", "given": "Yun", "initials": "Y"}, {"family": "Magnusson", "given": "Patrik K E", "initials": "PKE", "orcid": "0000-0002-7315-7899", "researcher": {"href": "https://publications.scilifelab.se/researcher/b277b6387de142bbab91fad82d9eff09.json"}}, {"family": "Gyllensten", "given": "Ulf", "initials": "U"}, {"family": "Hultman", "given": "Christina M", "initials": "CM"}, {"family": "Sullivan", "given": "Patrick F", "initials": "PF"}, {"family": "Szatkiewicz", "given": "Jin P", "initials": "JP", "orcid": "0000-0002-4898-7401", "researcher": {"href": "https://publications.scilifelab.se/researcher/eb39edd3c6c14938a47f1e22ecfea080.json"}}], "type": "journal article", "published": "2020-04-15", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "11", "issue": "1", "pages": "1842"}, "abstract": "Despite considerable progress in schizophrenia genetics, most findings have been for large rare structural variants and common variants in well-imputed regions with few genes implicated from exome sequencing. Whole genome sequencing (WGS) can potentially provide a more complete enumeration of etiological genetic variation apart from the exome and regions of high linkage disequilibrium. We analyze high-coverage WGS data from 1162 Swedish schizophrenia cases and 936 ancestry-matched population controls. Our main objective is to evaluate the contribution to schizophrenia etiology from a variety of genetic variants accessible to WGS but not by previous technologies. Our results suggest that ultra-rare structural variants that affect the boundaries of topologically associated domains (TADs) increase risk for schizophrenia. Alterations in TAD boundaries may lead to dysregulation of gene expression. Future mechanistic studies will be needed to determine the precise functional effects of these variants on biology.", "doi": "10.1038/s41467-020-15707-w", "pmid": "32296054", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "NGI Uppsala (Uppsala Genome Center)": "Collaborative", "Systems Biology": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-15707-w"}, {"db": "pmc", "key": "PMC7160146"}], "notes": [], "created": "2020-04-20T06:46:04.706Z", "modified": "2024-01-16T13:48:42.613Z"}, {"entity": "publication", "iuid": "a750ac0e1638402895c1d97a8ac2528b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a750ac0e1638402895c1d97a8ac2528b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a750ac0e1638402895c1d97a8ac2528b"}}, "title": "Effect of sample preparation techniques upon single cell chemical imaging: A practical comparison between synchrotron radiation based X-ray fluorescence (SR-XRF) and Nanoscopic Secondary Ion Mass Spectrometry (nano-SIMS).", "authors": [{"family": "De Samber", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "De Rycke", "given": "Riet", "initials": "R"}, {"family": "De Bruyne", "given": "Michiel", "initials": "M"}, {"family": "Kienhuis", "given": "Michiel", "initials": "M"}, {"family": "Sandblad", "given": "Linda", "initials": "L", "orcid": "0000-0003-3492-3287", "researcher": {"href": "https://publications.scilifelab.se/researcher/070825e0190a4e9a932e79663d2bc89f.json"}}, {"family": "Bohic", "given": "Sylvain", "initials": "S"}, {"family": "Cloetens", "given": "Peter", "initials": "P"}, {"family": "Urban", "given": "Constantin", "initials": "C"}, {"family": "Polerecky", "given": "Lubos", "initials": "L"}, {"family": "Vincze", "given": "Laszlo", "initials": "L"}], "type": "comparative study", "published": "2020-04-15", "journal": {"volume": "1106", "issn": "1873-4324", "issue": null, "pages": "22-32", "title": "Anal. Chim. Acta", "issn-l": "0003-2670"}, "abstract": "Analytical capabilities of Nanoscopic Secondary Ion Mass Spectrometry (nano-SIMS) and Synchrotron Radiation based X-ray Fluorescence (SR nano-XRF) techniques were compared for nanochemical imaging of polymorphonuclear human neutrophils (PMNs). PMNs were high pressure frozen (HPF), cryo-substituted, embedded in Spurr's resin and cut in thin sections (500 nm and 2 \u03bcm for both techniques resp.) Nano-SIMS enabled nanoscale mapping of isotopes of C, N, O, P and S, while SR based nano-XRF enabled trace level imaging of metals like Ca, Mn, Fe, Ni, Cu and Zn at a resolution of approx. 50 nm. The obtained elemental distributions were compared with those of whole, cryofrozen PMNs measured at the newly developed ID16A nano-imaging beamline at the European Synchrotron Radiation Facility (ESRF) in Grenoble, France. Similarities were observed for elements more tightly bound to the cell structure such as phosphorus and sulphur, while differences for mobile ions such as chlorine and potassium were more pronounced. Due to the observed elemental redistribution of mobile ions such as potassium and chlorine, elemental analysis of high pressure frozen (HPF), cryo-substituted and imbedded cells should be interpreted critically. Although decreasing analytical sensitivity occurs due to the presence of ice, analysis of cryofrozen cells - close to their native state - remains the golden standard. In general, we found nanoscale secondary ion mass spectrometry (nano-SIMS) and synchrotron radiation based nanoscopic X-ray fluorescence (SR nano-XRF) to be two supplementary alternatives for nanochemical imaging of single cells at the nanoscale.", "doi": "10.1016/j.aca.2020.01.054", "pmid": "32145852", "labels": {"Cryo-EM": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0003-2670(20)30107-0"}], "notes": [], "created": "2020-02-14T09:44:33.634Z", "modified": "2022-04-01T14:58:51.821Z"}, {"entity": "publication", "iuid": "641969a706f64f77a960eb7a359de6c4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/641969a706f64f77a960eb7a359de6c4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/641969a706f64f77a960eb7a359de6c4"}}, "title": "Difference in virulence between Neisseria meningitidis serogroups W and Y in transgenic mice.", "authors": [{"family": "Eriksson", "given": "Lorraine", "initials": "L"}, {"family": "Stenmark", "given": "Bianca", "initials": "B", "orcid": "0000-0003-4637-8626", "researcher": {"href": "https://publications.scilifelab.se/researcher/726c71c7aca148c981b48bde574a2e1c.json"}}, {"family": "Deghmane", "given": "Ala-Eddine", "initials": "A"}, {"family": "Thulin Hedberg", "given": "Sara", "initials": "S"}, {"family": "S\u00e4ll", "given": "Olof", "initials": "O"}, {"family": "Fredlund", "given": "Hans", "initials": "H"}, {"family": "M\u00f6lling", "given": "Paula", "initials": "P"}, {"family": "Taha", "given": "Muhamed-Kheir", "initials": "M"}], "type": "comparative study", "published": "2020-04-15", "journal": {"title": "BMC Microbiol.", "issn": "1471-2180", "issn-l": "1471-2180", "volume": "20", "issue": "1", "pages": "92"}, "abstract": "Neisseria meningitidis serogroups W and Y are the most common serogroups causing invasive meningococcal disease in Sweden. The majority of cases are caused by the serogroup W UK 2013 strain of clonal complex (cc) 11, and subtype 1 of the serogroup Y, YI strain of cc23. In this study, virulence factors of several lineages within cc11 and cc23 were investigated in transgenic BALB/c mice expressing human transferrin. Transgenic mice were infected intraperitoneally with serogroup W and Y isolates. Levels of bacteria and the proinflammatory cytokine CXCL1 were determined in blood collected 3 h and 24 h post-infection. Apoptosis was investigated in immune cells from peritoneal washes of infected mice. Adhesion and induction of apoptosis in human epithelial cells were also scored.\r\n\r\nThe levels of bacteraemia, CXCL1, and apoptosis were higher in serogroup W infected mice than in serogroup Y infected mice. Serogroup W isolates also induced higher levels of apoptosis and adhesion in human epithelial cells. No significant differences were observed between different lineages within cc11 and cc23.\r\n\r\nN. meningitidis Serogroup W displayed a higher virulence in vivo in transgenic mice, compared to serogroup Y. This was reflected by higher bacteremia, proinflammatory activity, and ability to induce apoptosis in mouse immune cells and human epithelial cells.", "doi": "10.1186/s12866-020-01760-4", "pmid": "32295520", "labels": {"Clinical Genomics \u00d6rebro": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1186/s12866-020-01760-4"}, {"db": "pmc", "key": "PMC7160935"}], "notes": [], "created": "2020-11-27T13:57:27.487Z", "modified": "2021-12-08T12:31:42.333Z"}, {"entity": "publication", "iuid": "4914e822a6ff4ce4ad8cafdded9ef574", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4914e822a6ff4ce4ad8cafdded9ef574.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4914e822a6ff4ce4ad8cafdded9ef574"}}, "title": "Automation of Spatial Transcriptomics library preparation to enable rapid and robust insights into spatial organization of tissues.", "authors": [{"family": "Berglund", "given": "Emelie", "initials": "E"}, {"family": "Saarenp\u00e4\u00e4", "given": "Sami", "initials": "S"}, {"family": "Jemt", "given": "Anders", "initials": "A"}, {"family": "Gruselius", "given": "Joel", "initials": "J"}, {"family": "Larsson", "given": "Ludvig", "initials": "L"}, {"family": "Bergenstr\u00e5hle", "given": "Ludvig", "initials": "L"}, {"family": "Lundeberg", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4313-1601", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a4e6ca0f29b4ead8569e2729481c3e0.json"}}, {"family": "Giacomello", "given": "Stefania", "initials": "S", "orcid": "0000-0003-0738-1574", "researcher": {"href": "https://publications.scilifelab.se/researcher/8499e792cc394c42b4240ef5fb3fd06c.json"}}], "type": "journal article", "published": "2020-04-15", "journal": {"title": "BMC Genomics", "issn": "1471-2164", "volume": "21", "issue": "1", "pages": "298", "issn-l": "1471-2164"}, "abstract": "Interest in studying the spatial distribution of gene expression in tissues is rapidly increasing. Spatial Transcriptomics is a novel sequencing-based technology that generates high-throughput information on the distribution, heterogeneity and co-expression of cells in tissues. Unfortunately, manual preparation of high-quality sequencing libraries is time-consuming and subject to technical variability due to human error during manual pipetting, which results in sample swapping and the accidental introduction of batch effects. All these factors complicate the production and interpretation of biological datasets.\n\nWe have integrated an Agilent Bravo Automated Liquid Handling Platform into the Spatial Transcriptomics workflow. Compared to the previously reported Magnatrix 8000+ automated protocol, this approach increases the number of samples processed per run, reduces sample preparation time by 35%, and minimizes batch effects between samples. The new approach is also shown to be highly accurate and almost completely free from technical variability between prepared samples.\n\nThe new automated Spatial Transcriptomics protocol using the Agilent Bravo Automated Liquid Handling Platform rapidly generates high-quality Spatial Transcriptomics libraries. Given the wide use of the Agilent Bravo Automated Liquid Handling Platform in research laboratories and facilities, this will allow many researchers to quickly create robust Spatial Transcriptomics libraries.", "doi": "10.1186/s12864-020-6631-z", "pmid": "32293264", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12864-020-6631-z"}, {"db": "pmc", "key": "PMC7158132"}], "notes": [], "created": "2020-07-08T13:03:44.517Z", "modified": "2024-01-16T13:48:42.620Z"}, {"entity": "publication", "iuid": "6733f592fb4a45bf9135c7dcc59e9c3d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6733f592fb4a45bf9135c7dcc59e9c3d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6733f592fb4a45bf9135c7dcc59e9c3d"}}, "title": "Generation of Retinal Pigment Epithelial Cells Derived from Human Embryonic Stem Cells Lacking Human Leukocyte Antigen Class I and II.", "authors": [{"family": "Petrus-Reurer", "given": "Sandra", "initials": "S"}, {"family": "Winblad", "given": "Nerges", "initials": "N"}, {"family": "Kumar", "given": "Pankaj", "initials": "P"}, {"family": "Gorchs", "given": "Laia", "initials": "L"}, {"family": "Chrobok", "given": "Michael", "initials": "M"}, {"family": "Wagner", "given": "Arnika Kathleen", "initials": "AK"}, {"family": "Bartuma", "given": "Hammurabi", "initials": "H"}, {"family": "Lardner", "given": "Emma", "initials": "E"}, {"family": "Aronsson", "given": "Monica", "initials": "M"}, {"family": "Plaza Reyes", "given": "\u00c1lvaro", "initials": "\u00c1"}, {"family": "Andr\u00e9", "given": "Helder", "initials": "H"}, {"family": "Alici", "given": "Evren", "initials": "E"}, {"family": "Kaipe", "given": "Helen", "initials": "H"}, {"family": "Kvanta", "given": "Anders", "initials": "A"}, {"family": "Lanner", "given": "Fredrik", "initials": "F"}], "type": "journal article", "published": "2020-04-14", "journal": {"title": "Stem Cell Reports", "issn": "2213-6711", "volume": "14", "issue": "4", "pages": "648-662", "issn-l": "2213-6711"}, "abstract": "Human embryonic stem cell-derived retinal pigment epithelial (hESC-RPE) cells could serve as a replacement therapy in advanced stages of age-related macular degeneration. However, allogenic hESC-RPE transplants trigger immune rejection, supporting a strategy to evade their immune recognition. We established single-knockout beta-2 microglobulin (SKO-B2M), class II major histocompatibility complex transactivator (SKO-CIITA) and double-knockout (DKO) hESC lines that were further differentiated into corresponding hESC-RPE lines lacking either surface human leukocyte antigen class I (HLA-I) or HLA-II, or both. Activation of CD4+ and CD8+ T-cells was markedly lower by hESC-RPE DKO cells, while natural killer cell cytotoxic response was not increased. After transplantation of SKO-B2M, SKO-CIITA, or DKO hESC-RPEs in a preclinical rabbit model, donor cell rejection was reduced and delayed. In conclusion, we have developed cell lines that lack both HLA-I and -II antigens, which evoke reduced T-cell responses in vitro together with reduced rejection in a large-eyed animal model.", "doi": "10.1016/j.stemcr.2020.02.006", "pmid": "32197113", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S2213-6711(20)30062-X"}, {"db": "pmc", "key": "PMC7160308"}], "notes": [], "created": "2020-07-08T13:05:34.265Z", "modified": "2024-01-16T13:48:42.627Z"}, {"entity": "publication", "iuid": "ca0a1a89785f44708ab634c2b1b2b13c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ca0a1a89785f44708ab634c2b1b2b13c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ca0a1a89785f44708ab634c2b1b2b13c"}}, "title": "MutT homologue 1 (MTH1) removes N6-methyl-dATP from the dNTP pool.", "authors": [{"family": "Scaletti", "given": "Emma Rose", "initials": "ER"}, {"family": "Vallin", "given": "Karl S", "initials": "KS"}, {"family": "Br\u00e4utigam", "given": "Lars", "initials": "L"}, {"family": "Sarno", "given": "Antonio", "initials": "A", "orcid": "0000-0002-9308-8018", "researcher": {"href": "https://publications.scilifelab.se/researcher/f47cb410dce04c30bf70b85c6633d72f.json"}}, {"family": "Warpman Berglund", "given": "Ulrika", "initials": "U"}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications.scilifelab.se/researcher/d97eba9f5edf4d76a5259c4baa8366c5.json"}}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS", "orcid": "0000-0002-7550-1833", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd07c6c543544af1a904e039f73ba857.json"}}], "type": "journal article", "published": "2020-04-10", "journal": {"title": "J. Biol. Chem.", "issn": "1083-351X", "volume": "295", "issue": "15", "pages": "4761-4772", "issn-l": "0021-9258"}, "abstract": "MutT homologue 1 (MTH1) removes oxidized nucleotides from the nucleotide pool and thereby prevents their incorporation into the genome and thereby reduces genotoxicity. We previously reported that MTH1 is an efficient catalyst of O6-methyl-dGTP hydrolysis suggesting that MTH1 may also sanitize the nucleotide pool from other methylated nucleotides. We here show that MTH1 efficiently catalyzes the hydrolysis of N6-methyl-dATP to N6-methyl-dAMP and further report that N6-methylation of dATP drastically increases the MTH1 activity. We also observed MTH1 activity with N6-methyl-ATP, albeit at a lower level. We show that N6-methyl-dATP is incorporated into DNA in vivo, as indicated by increased N6-methyl-dA DNA levels in embryos developed from MTH1 knock-out zebrafish eggs microinjected with N6-methyl-dATP compared with noninjected embryos. N6-methyl-dATP activity is present in MTH1 homologues from distantly related vertebrates, suggesting evolutionary conservation and indicating that this activity is important. Of note, N6-methyl-dATP activity is unique to MTH1 among related NUDIX hydrolases. Moreover, we present the structure of N6-methyl-dAMP-bound human MTH1, revealing that the N6-methyl group is accommodated within a hydrophobic active-site subpocket explaining why N6-methyl-dATP is a good MTH1 substrate. N6-methylation of DNA and RNA has been reported to have epigenetic roles and to affect mRNA metabolism. We propose that MTH1 acts in concert with adenosine deaminase-like protein isoform 1 (ADAL1) to prevent incorporation of N6-methyl-(d)ATP into DNA and RNA. This would hinder potential dysregulation of epigenetic control and RNA metabolism via conversion of N6-methyl-(d)ATP to N6-methyl-(d)AMP, followed by ADAL1-catalyzed deamination producing (d)IMP that can enter the nucleotide salvage pathway.", "doi": "10.1074/jbc.RA120.012636", "pmid": "32144205", "labels": {"Protein Science Facility (PSF)": "Service"}, "xrefs": [{"db": "pii", "key": "S0021-9258(17)48573-5"}, {"db": "pmc", "key": "PMC7152754"}, {"db": "PDB", "key": "3ZR1"}, {"db": "PDB", "key": "3ZR0"}, {"db": "PDB", "key": "5OTM"}, {"db": "PDB", "key": "6QVO"}, {"db": "PDB", "key": "5OTN"}, {"db": "PDB", "key": "6FL4"}, {"db": "PDB", "key": "3A6T"}], "notes": [], "created": "2020-03-12T14:06:48.859Z", "modified": "2021-11-10T12:52:10.141Z"}, {"entity": "publication", "iuid": "d35dda9e1c1e4f48ae002543b503d001", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d35dda9e1c1e4f48ae002543b503d001.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d35dda9e1c1e4f48ae002543b503d001"}}, "title": "Ex Vivo Organoid Cultures Reveal the Importance of the Tumor Microenvironment for Maintenance of Colorectal Cancer Stem Cells.", "authors": [{"family": "Li", "given": "Xingru", "initials": "X"}, {"family": "Larsson", "given": "P\u00e4r", "initials": "P", "orcid": "0000-0001-9054-5191", "researcher": {"href": "https://publications.scilifelab.se/researcher/573c6350305a49cba2ac0798dea21ae0.json"}}, {"family": "Ljuslinder", "given": "Ingrid", "initials": "I"}, {"family": "\u00d6hlund", "given": "Daniel", "initials": "D", "orcid": "0000-0002-5847-2778", "researcher": {"href": "https://publications.scilifelab.se/researcher/42e9e473f68c460098a37e22d0a41369.json"}}, {"family": "Myte", "given": "Robin", "initials": "R"}, {"family": "L\u00f6fgren-Burstr\u00f6m", "given": "Anna", "initials": "A"}, {"family": "Zingmark", "given": "Carl", "initials": "C"}, {"family": "Ling", "given": "Agnes", "initials": "A"}, {"family": "Edin", "given": "Sofia", "initials": "S"}, {"family": "Palmqvist", "given": "Richard", "initials": "R", "orcid": "0000-0002-9933-2843", "researcher": {"href": "https://publications.scilifelab.se/researcher/40ae823e5364458b8f957a65a82c741f.json"}}], "type": "journal article", "published": "2020-04-10", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "issn-l": "2072-6694", "volume": "12", "issue": "4", "pages": "923"}, "abstract": "Colorectal cancer (CRC) is a heterogeneous disease, with varying clinical presentations and patient prognosis. Different molecular subgroups of CRC should be treated differently and therefore, must be better characterized. Organoid culture has recently been suggested as a good model to reflect the heterogeneous nature of CRC. However, organoid cultures cannot be established from all CRC tumors. The study examines which CRC tumors are more likely to generate organoids and thus benefit from ex vivo organoid drug testing. Long-term organoid cultures from 22 out of 40 CRC tumor specimens were established. It was found that organoid cultures were more difficult to establish from tumors characterized as microsatellite instable (MSI), BRAF-mutated, poorly differentiated and/or of a mucinous type. This suggests that patients with such tumors are less likely to benefit from ex vivo organoid drug testing, but it may also suggest biological difference in tumor growth. RNA sequencing analysis of tumor sections revealed that the in vivo maintenance of these non-organoid-forming tumors depends on factors related to inflammation and pathogen exposure. Furthermore, using TCGA data we could show a trend towards a worse prognosis for patients with organoid-forming tumors, suggesting also clinical differences. Results suggest that organoids are more difficult to establish from tumors characterized as MSI, BRAF-mutated, poorly differentiated and/or of a mucinous type. We further suggest that the maintenance of cell growth of these tumors in vivo may be promoted by immune-related factors and other stromal components within the tumor microenvironment.", "doi": "10.3390/cancers12040923", "pmid": "32290033", "labels": {"Clinical Genomics Ume\u00e5": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "cancers12040923"}, {"db": "pmc", "key": "PMC7226030"}], "notes": [], "created": "2021-06-18T11:54:38.900Z", "modified": "2021-12-08T14:16:21.865Z"}, {"entity": "publication", "iuid": "348be40f9f6a4ce29625b02c375ccea8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/348be40f9f6a4ce29625b02c375ccea8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/348be40f9f6a4ce29625b02c375ccea8"}}, "title": "Hybrid Aspen Expressing a Carbohydrate Esterase Family 5 Acetyl Xylan Esterase Under Control of a Wood-Specific Promoter Shows Improved Saccharification.", "authors": [{"family": "Wang", "given": "Zhao", "initials": "Z"}, {"family": "Pawar", "given": "Prashant Mohan-Anupama", "initials": "PM"}, {"family": "Derba-Maceluch", "given": "Marta", "initials": "M"}, {"family": "Hedenstr\u00f6m", "given": "Mattias", "initials": "M"}, {"family": "Chong", "given": "Sun-Li", "initials": "SL"}, {"family": "Tenkanen", "given": "Maija", "initials": "M"}, {"family": "J\u00f6nsson", "given": "Leif J", "initials": "LJ"}, {"family": "Mellerowicz", "given": "Ewa J", "initials": "EJ"}], "type": "journal article", "published": "2020-04-08", "journal": {"title": "Front Plant Sci", "issn": "1664-462X", "volume": "11", "issue": null, "pages": "380", "issn-l": "1664-462X"}, "abstract": "Fast-growing broad-leaf tree species can serve as feedstocks for production of bio-based chemicals and fuels through biochemical conversion of wood to monosaccharides. This conversion is hampered by the xylan acetylation pattern. To reduce xylan acetylation in the wood, the Hypocrea jecorina acetyl xylan esterase (HjAXE) from carbohydrate esterase (CE) family 5 was expressed in hybrid aspen under the control of the wood-specific PtGT43B promoter and targeted to the secretory pathway. The enzyme was predicted to deacetylate polymeric xylan in the vicinity of cellulose due to the presence of a cellulose-binding module. Cell-wall-bound protein fractions from developing wood of transgenic plants were capable of releasing acetyl from finely ground wood powder, indicative of active AXE present in cell walls of these plants, whereas no such activity was detected in wild-type plants. The transgenic lines grew in height and diameter as well as wild-type trees, whereas their internodes were slightly shorter, indicating higher leaf production. The average acetyl content in the wood of these lines was reduced by 13%, mainly due to reductions in di-acetylated xylose units, and in C-2 and C-3 mono-acetylated xylose units. Analysis of soluble cell wall polysaccharides revealed a 4% reduction in the fraction of xylose units and an 18% increase in the fraction of glucose units, whereas the contents of cellulose and lignin were not affected. Enzymatic saccharification of wood from transgenic plants resulted in 27% higher glucose yield than for wild-type plants. Brunauer-Emmett-Teller (BET) analysis and Simons' staining pointed toward larger surface area and improved cellulose accessibility for wood from transgenic plants compared to wood from wild-type plants, which could be achieved by HjAXE deacetylating xylan bound to cellulose. The results show that CE5 family can serve as a source of enzymes for in planta reduction of recalcitrance to saccharification.", "doi": "10.3389/fpls.2020.00380", "pmid": "32322259", "labels": {"Swedish NMR Centre": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC7156598"}], "notes": [], "created": "2020-11-24T20:26:42.680Z", "modified": "2025-10-17T13:03:57.020Z"}, {"entity": "publication", "iuid": "e6f9553d26ec4221bb4d1f05a3b730ae", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e6f9553d26ec4221bb4d1f05a3b730ae.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e6f9553d26ec4221bb4d1f05a3b730ae"}}, "title": "Building blocks are synthesized on demand during the yeast cell cycle.", "authors": [{"family": "Campbell", "given": "Kate", "initials": "K", "orcid": "0000-0002-4173-5260", "researcher": {"href": "https://publications.scilifelab.se/researcher/53ae98fe046c4351bf11ab1c23f5bc1e.json"}}, {"family": "Westholm", "given": "Jakub", "initials": "J", "orcid": "0000-0002-6849-6220", "researcher": {"href": "https://publications.scilifelab.se/researcher/161d8b5fb6734b33ad5f5590edbc0cff.json"}}, {"family": "Kasvandik", "given": "Sergo", "initials": "S", "orcid": "0000-0003-0218-2410", "researcher": {"href": "https://publications.scilifelab.se/researcher/51fff3733988455ca143eea61518ee49.json"}}, {"family": "Di Bartolomeo", "given": "Francesca", "initials": "F", "orcid": "0000-0002-4302-0701", "researcher": {"href": "https://publications.scilifelab.se/researcher/b4c0751743614b88b7034e04a81f3ee9.json"}}, {"family": "Mormino", "given": "Maurizio", "initials": "M", "orcid": "0000-0003-2055-5081", "researcher": {"href": "https://publications.scilifelab.se/researcher/6bfdb794959c4feeb11d6e12d68efc06.json"}}, {"family": "Nielsen", "given": "Jens", "initials": "J", "orcid": "0000-0002-9955-6003", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a596e289be4438a8a2653b1f25fea8b.json"}}], "type": "journal article", "published": "2020-04-07", "journal": {"title": "Proc. Natl. Acad. Sci. U.S.A.", "issn": "1091-6490", "issn-l": "0027-8424", "volume": "117", "issue": "14", "pages": "7575-7583"}, "abstract": "For cells to replicate, a sufficient supply of biosynthetic precursors is needed, necessitating the concerted action of metabolism and protein synthesis during progressive phases of cell division. A global understanding of which biosynthetic processes are involved and how they are temporally regulated during replication is, however, currently lacking. Here, quantitative multiomics analysis is used to generate a holistic view of the eukaryal cell cycle, using the budding yeast Saccharomyces cerevisiae Protein synthesis and central carbon pathways such as glycolysis and amino acid metabolism are shown to synchronize their respective abundance profiles with division, with pathway-specific changes in metabolite abundance also being reflected by a relative increase in mitochondrial volume, as shown by quantitative fluorescence microscopy. These results show biosynthetic precursor production to be temporally regulated to meet phase-specific demands of eukaryal cell division.", "doi": "10.1073/pnas.1919535117", "pmid": "32213592", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "Systems Biology": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "1919535117"}, {"db": "pmc", "key": "PMC7149230"}], "notes": [], "created": "2020-04-23T08:46:36.785Z", "modified": "2021-11-10T12:52:17.737Z"}, {"entity": "publication", "iuid": "f5c4593d66bd47b7b8c4b6ec46b98e11", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f5c4593d66bd47b7b8c4b6ec46b98e11.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f5c4593d66bd47b7b8c4b6ec46b98e11"}}, "title": "The honeybee (Apis mellifera) developmental state shapes the genetic composition of the deformed wing virus-A quasispecies during serial transmission.", "authors": [{"family": "Ya\u00f1ez", "given": "Orlando", "initials": "O", "orcid": "0000-0001-8493-2726", "researcher": {"href": "https://publications.scilifelab.se/researcher/e202e4f4253b4e6f91d6f3bfcf8247cb.json"}}, {"family": "Ch\u00e1vez-Galarza", "given": "Julio", "initials": "J"}, {"family": "Tellgren-Roth", "given": "Christian", "initials": "C", "orcid": "0000-0003-0502-3693", "researcher": {"href": "https://publications.scilifelab.se/researcher/982873aade554b38b26b877298db5115.json"}}, {"family": "Pinto", "given": "M Alice", "initials": "MA", "orcid": "0000-0001-9663-8399", "researcher": {"href": "https://publications.scilifelab.se/researcher/62c4785cb6714a09be0ec688ed4fce92.json"}}, {"family": "Neumann", "given": "Peter", "initials": "P"}, {"family": "de Miranda", "given": "Joachim R", "initials": "JR", "orcid": "0000-0002-0335-0386", "researcher": {"href": "https://publications.scilifelab.se/researcher/d0bd25adff9b48e694c30279d0db901b.json"}}], "type": "journal article", "published": "2020-04-06", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "5956", "issn-l": "2045-2322"}, "abstract": "The main biological threat to the western honeybee (Apis mellifera) is the parasitic mite Varroa destructor, largely because it vectors lethal epidemics of honeybee viruses that, in the absence of this mite, are relatively innocuous. The severe pathology is a direct consequence of excessive virus titres caused by this novel transmission route. However, little is known about how the virus adapts genetically during transmission and whether this influences the pathology. Here, we show that upon injection into honeybee pupae, the deformed wing virus type-A (DWV-A) quasispecies undergoes a rapid, extensive expansion of its sequence space, followed by strong negative selection towards a uniform, common shape by the time the pupae have completed their development, with no difference between symptomatic and asymptomatic adults in either DWV titre or genetic composition. This suggests that the physiological and molecular environment during pupal development has a strong, conservative influence on shaping the DWV-A quasispecies in emerging adults. There was furthermore no evidence of any progressive adaptation of the DWV-A quasispecies to serial intra-abdominal injection, simulating mite transmission, despite the generation of ample variation immediately following each transmission, suggesting that the virus either had already adapted to transmission by injection, or was unaffected by it.", "doi": "10.1038/s41598-020-62673-w", "pmid": "32249797", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Collaborative", "National Genomics Infrastructure": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-62673-w"}, {"db": "pmc", "key": "PMC7136270"}], "notes": [], "created": "2020-09-15T07:19:57.145Z", "modified": "2024-01-16T13:48:42.634Z"}, {"entity": "publication", "iuid": "db1ed54638e64638ab235cfb62758387", "links": {"self": {"href": "https://publications.scilifelab.se/publication/db1ed54638e64638ab235cfb62758387.json"}, "display": {"href": "https://publications.scilifelab.se/publication/db1ed54638e64638ab235cfb62758387"}}, "title": "Draft Genome Sequence of the Urinary Catheter Isolate Enterobacter ludwigii CEB04 with High Biofilm Forming Capacity.", "authors": [{"family": "Shafeeq", "given": "Sulman", "initials": "S"}, {"family": "Wang", "given": "Xiaoda", "initials": "X", "orcid": "0000-0003-0175-435X", "researcher": {"href": "https://publications.scilifelab.se/researcher/6a7de54a021a47f09821f26fb4ee2f4e.json"}}, {"family": "L\u00fcnsdorf", "given": "Heinrich", "initials": "H"}, {"family": "Brauner", "given": "Annelie", "initials": "A"}, {"family": "R\u00f6mling", "given": "Ute", "initials": "U", "orcid": "0000-0003-3812-6621", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a59ac735d61485aa43ee7a2ae3a526d.json"}}], "type": "journal article", "published": "2020-04-05", "journal": {"volume": "8", "issn": "2076-2607", "issue": "4", "title": "Microorganisms", "pages": "522", "issn-l": "2076-2607"}, "abstract": ": Enterobacter ludwigii is a fermentative Gram-negative environmental species and accidental human pathogen that belongs to the Enterobacter cloacae complex with the general characteristics of the genus Enterobacter. The clinical isolate E. ludwigii CEB04 was derived from a urinary tract catheter of an individual not suffering from catheter-associated urinary tract infection. The draft genome sequence of the high biofilm forming E. ludwigii CEB04 was determined by PacBio sequencing. The chromosome of E. ludwigii CEB04 is comprised of one contig of 4,892,375 bps containing 4596 predicted protein-coding genes and 120 noncoding RNAs. E. ludwigii CEB04 harbors several antimicrobial resistance markers and has an extended cyclic-di-GMP signaling network compared to Escherichia coli K-12.", "doi": "10.3390/microorganisms8040522", "pmid": "32260576", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service", "Bioinformatics Support, Infrastructure and Training": "Service", "Bioinformatics Support and Infrastructure": "Service", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7232144"}, {"db": "pii", "key": "microorganisms8040522"}], "notes": [], "created": "2020-05-04T14:34:04.659Z", "modified": "2024-01-16T13:48:42.641Z"}, {"entity": "publication", "iuid": "b8409eb1124c41258c01b678e729e7e6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b8409eb1124c41258c01b678e729e7e6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b8409eb1124c41258c01b678e729e7e6"}}, "title": "The conifer root rot pathogens Heterobasidion irregulare and Heterobasidion occidentale employ different strategies to infect Norway spruce.", "authors": [{"family": "Hu", "given": "Yang", "initials": "Y"}, {"family": "Elfstrand", "given": "Malin", "initials": "M"}, {"family": "Stenlid", "given": "Jan", "initials": "J"}, {"family": "Durling", "given": "Mikael Brandstr\u00f6m", "initials": "MB", "orcid": "0000-0001-6485-197X", "researcher": {"href": "https://publications.scilifelab.se/researcher/7be72d0dcc48489495509b23c7ad3d38.json"}}, {"family": "Olson", "given": "\u00c5ke", "initials": "\u00c5", "orcid": "0000-0001-8998-6096", "researcher": {"href": "https://publications.scilifelab.se/researcher/83a79139c2b94d9f97cf038e1cab8c03.json"}}], "type": "journal article", "published": "2020-04-03", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "5884", "issn-l": "2045-2322"}, "abstract": "Heterobasidion irregulare and H. occidentale are two closely related conifer root rot pathogens in the H. annosum sensu lato (s.l.) species complex. The two species H. irregulare and H. occidentale have different host preference with pine and non-pine tree species favored, respectively. The comparison of transcriptomes of H. irregulare and H. occidentale growing in Norway spruce bark, a susceptible host non-native to North America, showed large differences in gene expression. Heterobasidion irregulare induced more genes involved in detoxification of host compounds and in production of secondary metabolites, while the transcriptome induced in H. occidentale was more oriented towards carbohydrate degradation. Along with their separated evolutionary history, the difference might be driven by their host preferences as indicated by the differentially expressed genes enriched in particular Gene Ontology terms.", "doi": "10.1038/s41598-020-62521-x", "pmid": "32246017", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-62521-x"}, {"db": "pmc", "key": "PMC7125170"}], "notes": [], "created": "2020-07-03T05:24:05.280Z", "modified": "2024-01-16T13:48:42.649Z"}, {"entity": "publication", "iuid": "411b0e8ddd4f4cf98234230c57fb780c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/411b0e8ddd4f4cf98234230c57fb780c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/411b0e8ddd4f4cf98234230c57fb780c"}}, "title": "Plant resistance does not compromise parasitoid-based biocontrol of a strawberry pest.", "authors": [{"family": "Weber", "given": "Daniela", "initials": "D"}, {"family": "Egan", "given": "Paul A", "initials": "PA"}, {"family": "Muola", "given": "Anne", "initials": "A"}, {"family": "Ericson", "given": "Lars E", "initials": "LE"}, {"family": "Stenberg", "given": "Johan A", "initials": "JA"}], "type": "journal article", "published": "2020-04-03", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "5899", "issn-l": "2045-2322"}, "abstract": "Plant nutritional quality can influence interactions between herbivores and their parasitoids. While most previous work has focused on a limited set of secondary plant metabolites, the tri-trophic effects of overall phenotypic resistance have been understudied. Furthermore, the joint effects of secondary and primary metabolites on parasitoids are almost unexplored. In this study, we compared the performance and survival of the parasitoid species Asecodes parviclava Thompson on wild woodland strawberry (Fragaria vesca L.) genotypes showing variation in resistance against the parasitoid's host, the strawberry leaf beetle (Galerucella tenella L.). Additionally, we related the metabolic profiles of these plant genotypes to the tritrophic outcomes in order to identify primary and secondary metabolites involved in regulating plant potential to facilitate parasitism. We found that parasitoid performance was strongly affected by plant genotype, but those differences in plant resistance to the herbivore were not reflected in parasitoid survival. These findings could be explained in particular by a significant link between parasitoid survival and foliar carbohydrate levels, which appeared to be the most important compounds for parasitism success. The fact that plant quality strongly affects parasitism should be further explored and utilized in plant breeding programs for a synergistic application in sustainable pest management.", "doi": "10.1038/s41598-020-62698-1", "pmid": "32246069", "labels": {"Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-62698-1"}, {"db": "pmc", "key": "PMC7125231"}], "notes": [], "created": "2020-12-11T12:05:25.341Z", "modified": "2025-10-17T13:03:16.868Z"}, {"entity": "publication", "iuid": "3be06852b34541608682142085a5994e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3be06852b34541608682142085a5994e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3be06852b34541608682142085a5994e"}}, "title": "Guidelines for curriculum and course development in higher education and training", "authors": [{"family": "Tractenberg", "given": "Rochelle E", "initials": "RE", "orcid": "0000-0002-1121-2119", "researcher": {"href": "https://publications.scilifelab.se/researcher/d3f723902e7a4dda832e618662b86c4a.json"}}, {"family": "Lindvall", "given": "Jessica M", "initials": "JM", "orcid": "0000-0002-5042-8481", "researcher": {"href": "https://publications.scilifelab.se/researcher/78debae1bc714b11a97ecf9e9656f1eb.json"}}, {"family": "Attwood", "given": "Teresa", "initials": "T", "orcid": "0000-0003-2409-4235", "researcher": {"href": "https://publications.scilifelab.se/researcher/25b583b3e23e42418781542fb1e1ce63.json"}}, {"family": "Via", "given": "Allegra", "initials": "A"}], "type": "posted-content", "published": "2020-04-03", "journal": {"title": "OSF", "issn": null, "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": null, "doi": "10.31235/osf.io/7qeht", "pmid": null, "labels": {"Bioinformatics Support and Infrastructure": null, "Bioinformatics Support, Infrastructure and Training": null, "Bioinformatics (NBIS)": null}, "xrefs": [], "notes": [], "created": "2020-12-15T09:14:26.722Z", "modified": "2025-12-18T20:06:37.352Z"}, {"entity": "publication", "iuid": "f96a5077385748b2a9baf3c7ce7dc352", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f96a5077385748b2a9baf3c7ce7dc352.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f96a5077385748b2a9baf3c7ce7dc352"}}, "title": "Genomic characterization and outcome of prosthetic joint infections caused by Staphylococcus aureus.", "authors": [{"family": "Wildeman", "given": "Peter", "initials": "P"}, {"family": "Tevell", "given": "Staffan", "initials": "S"}, {"family": "Eriksson", "given": "Carl", "initials": "C"}, {"family": "Lagos", "given": "Amaya Campillay", "initials": "AC"}, {"family": "S\u00f6derquist", "given": "Bo", "initials": "B"}, {"family": "Stenmark", "given": "Bianca", "initials": "B", "orcid": "0000-0003-4637-8626", "researcher": {"href": "https://publications.scilifelab.se/researcher/726c71c7aca148c981b48bde574a2e1c.json"}}], "type": "journal article", "published": "2020-04-03", "journal": {"title": "Sci Rep", "issn": "2045-2322", "issn-l": "2045-2322", "volume": "10", "issue": "1", "pages": "5938"}, "abstract": "Staphylococcus aureus is a commensal colonizing the skin and mucous membranes. It can also act as a pathogen, and is the most common microorganism isolated from prosthetic joint infections (PJIs). The aim of this study was to explore the genomic relatedness between commensal and PJI S. aureus strains as well as microbial traits and host-related risk factors for treatment failure. Whole-genome sequencing (WGS) was performed on S. aureus isolates obtained from PJIs (n = 100) and control isolates from nares (n = 101). Corresponding clinical data for the PJI patients were extracted from medical records. No PJI-specific clusters were found in the WGS phylogeny, and the distribution of the various clonal complexes and prevalence of virulence genes among isolates from PJIs and nares was almost equal. Isolates from patients with treatment success and failure were genetically very similar, while the presence of an antibiotic-resistant phenotype and the use of non-biofilm-active antimicrobial treatment were both associated with failure.In conclusion, commensal and PJI isolates of S. aureus in arthroplasty patients were genetically indistinguishable, suggesting that commensal S. aureus clones are capable of causing PJIs. Furthermore, no association between genetic traits and outcome could be demonstrated, stressing the importance of patient-related factors in the treatment of S. aureus PJIs.", "doi": "10.1038/s41598-020-62751-z", "pmid": "32246045", "labels": {"Clinical Genomics \u00d6rebro": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-62751-z"}, {"db": "pmc", "key": "PMC7125104"}], "notes": [], "created": "2020-11-27T13:56:08.647Z", "modified": "2021-12-08T12:31:56.319Z"}, {"entity": "publication", "iuid": "3d52c9ab12914a419feae20a6e446826", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3d52c9ab12914a419feae20a6e446826.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3d52c9ab12914a419feae20a6e446826"}}, "title": "Thermal Proteome Profiling Identifies Oxidative-Dependent Inhibition of the Transcription of Major Oncogenes as a New Therapeutic Mechanism for Select Anticancer Compounds.", "authors": [{"family": "Peuget", "given": "Sylvain", "initials": "S"}, {"family": "Zhu", "given": "Jiawei", "initials": "J"}, {"family": "Sanz", "given": "Gema", "initials": "G", "orcid": "0000-0002-6227-0431", "researcher": {"href": "https://publications.scilifelab.se/researcher/3353dc98689341b4824217786d1e3956.json"}}, {"family": "Singh", "given": "Madhurendra", "initials": "M"}, {"family": "Gaetani", "given": "Massimiliano", "initials": "M", "orcid": "0000-0001-5610-0797", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b58e5cef5224fdcbdcd626fb798b169.json"}}, {"family": "Chen", "given": "Xinsong", "initials": "X"}, {"family": "Shi", "given": "Yao", "initials": "Y"}, {"family": "Saei", "given": "Amir Ata", "initials": "AA", "orcid": "0000-0002-2639-6328", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f1694ffdcd94a55b6c172a854706e0f.json"}}, {"family": "Visnes", "given": "Torkild", "initials": "T", "orcid": "0000-0003-1047-988X", "researcher": {"href": "https://publications.scilifelab.se/researcher/599a0da924424d098adc248b67fabf05.json"}}, {"family": "Lindstr\u00f6m", "given": "Mikael S", "initials": "MS", "orcid": "0000-0003-1148-8497", "researcher": {"href": "https://publications.scilifelab.se/researcher/5aa942fbfbee4257a129b3e7888f5b6d.json"}}, {"family": "Rihani", "given": "Ali", "initials": "A", "orcid": "0000-0002-6176-0519", "researcher": {"href": "https://publications.scilifelab.se/researcher/5dc94d95e8204181bf3e75354ec1678b.json"}}, {"family": "Moyano-Galceran", "given": "Lidia", "initials": "L", "orcid": "0000-0001-9219-6394", "researcher": {"href": "https://publications.scilifelab.se/researcher/085eed2a15bc4be08acbe21a18cb4e6c.json"}}, {"family": "Carlson", "given": "Joseph W", "initials": "JW", "orcid": "0000-0002-3006-4107", "researcher": {"href": "https://publications.scilifelab.se/researcher/cb81cad4b24d4692bc21bda7305f21f1.json"}}, {"family": "Hjerpe", "given": "Elisabet", "initials": "E"}, {"family": "Joneborg", "given": "Ulrika", "initials": "U"}, {"family": "Lehti", "given": "Kaisa", "initials": "K", "orcid": "0000-0001-9110-8719", "researcher": {"href": "https://publications.scilifelab.se/researcher/480c0e2b92df4dccbae3940721525345.json"}}, {"family": "Hartman", "given": "Johan", "initials": "J", "orcid": "0000-0002-6500-8527", "researcher": {"href": "https://publications.scilifelab.se/researcher/da7cefda6e00463d8ba95fc63eeb8f0a.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}, {"family": "Zubarev", "given": "Roman", "initials": "R", "orcid": "0000-0001-9839-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/e971b9cdec2b4411934f9c5d535da8b4.json"}}, {"family": "Selivanova", "given": "Galina", "initials": "G"}], "type": "journal article", "published": "2020-04-01", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "issn-l": "0008-5472", "volume": "80", "issue": "7", "pages": "1538-1550"}, "abstract": "Identification of the molecular mechanism of action (MoA) of bioactive compounds is a crucial step for drug development but remains a challenging task despite recent advances in technology. In this study, we applied multidimensional proteomics, sensitivity correlation analysis, and transcriptomics to identify a common MoA for the anticancer compounds RITA, aminoflavone (AF), and oncrasin-1 (Onc-1). Global thermal proteome profiling revealed that the three compounds target mRNA processing and transcription, thereby attacking a cancer vulnerability, transcriptional addiction. This led to the preferential loss of expression of oncogenes involved in PDGF, EGFR, VEGF, insulin/IGF/MAPKK, FGF, Hedgehog, TGF\u03b2, and PI3K signaling pathways. Increased reactive oxygen species level in cancer cells was a prerequisite for targeting the mRNA transcription machinery, thus conferring cancer selectivity to these compounds. Furthermore, DNA repair factors involved in homologous recombination were among the most prominently repressed proteins. In cancer patient samples, RITA, AF, and Onc-1 sensitized to poly(ADP-ribose) polymerase inhibitors both in vitro and ex vivo These findings might pave a way for new synthetic lethal combination therapies.Significance: These findings highlight agents that target transcriptional addiction in cancer cells and suggest combination treatments that target RNA processing and DNA repair pathways simultaneously as effective cancer therapies.", "doi": "10.1158/0008-5472.CAN-19-2069", "pmid": "32019870", "labels": {"Chemical Proteomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "0008-5472.CAN-19-2069"}], "notes": [], "created": "2020-02-07T22:52:26.989Z", "modified": "2024-01-18T23:48:25.871Z"}, {"entity": "publication", "iuid": "91e71a389adf4191a4bf1dfe8c6241b5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/91e71a389adf4191a4bf1dfe8c6241b5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/91e71a389adf4191a4bf1dfe8c6241b5"}}, "title": "Paralogization and New Protein Architectures in Planctomycetes Bacteria with Complex Cell Structures.", "authors": [{"family": "Mahajan", "given": "Mayank", "initials": "M"}, {"family": "Yee", "given": "Benjamin", "initials": "B"}, {"family": "H\u00e4gglund", "given": "Emil", "initials": "E"}, {"family": "Guy", "given": "Lionel", "initials": "L"}, {"family": "Fuerst", "given": "John A", "initials": "JA"}, {"family": "Andersson", "given": "Siv G E", "initials": "SGE"}], "type": "journal article", "published": "2020-04-01", "journal": {"title": "Mol. Biol. Evol.", "issn": "1537-1719", "volume": "37", "issue": "4", "pages": "1020-1040", "issn-l": "0737-4038"}, "abstract": "Bacteria of the phylum Planctomycetes have a unique cell plan with an elaborate intracellular membrane system, thereby resembling eukaryotic cells. The origin and evolution of these remarkable features is debated. To study the evolutionary genomics of bacteria with complex cell architectures, we have resequenced the 9.2-Mb genome of the model organism Gemmata obscuriglobus and sequenced the 10-Mb genome of G. massiliana Soil9, the 7.9-Mb genome of CJuql4, and the 6.7-Mb genome of Tuwongella immobilis, all of which belong to the family Gemmataceae. A gene flux analysis of the Planctomycetes revealed a massive emergence of novel protein families at multiple nodes within the Gemmataceae. The expanded protein families have unique multidomain architectures composed of domains that are characteristic of prokaryotes, such as the sigma factor domain of extracytoplasmic sigma factors, and domains that have proliferated in eukaryotes, such as the WD40, leucine-rich repeat, tetratricopeptide repeat and Ser/Thr kinase domains. Proteins with identifiable domains in the Gemmataceae have longer lengths and linkers than proteins in most other bacteria, and the analyses suggest that these traits were ancestrally present in the Planctomycetales. A broad comparison of protein length distribution profiles revealed an overlap between the longest proteins in prokaryotes and the shortest proteins in eukaryotes. We conclude that the many similarities between proteins in the Planctomycetales and the eukaryotes are due to convergent evolution and that there is no strict boundary between prokaryotes and eukaryotes with regard to features such as gene paralogy, protein length, and protein domain composition patterns.", "doi": "10.1093/molbev/msz287", "pmid": "31808939", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "5663460"}], "notes": [], "created": "2020-05-04T14:38:47.416Z", "modified": "2024-01-16T13:48:42.658Z"}, {"entity": "publication", "iuid": "c5b83f92647842f6b1ba31e14c3b1a39", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c5b83f92647842f6b1ba31e14c3b1a39.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c5b83f92647842f6b1ba31e14c3b1a39"}}, "title": "Lung developmental arrest caused by PDGF-A deletion: consequences for the adult mouse lung.", "authors": [{"family": "Gouveia", "given": "Leonor", "initials": "L", "orcid": "0000-0002-3825-8571", "researcher": {"href": "https://publications.scilifelab.se/researcher/883414ef5edf49fdab0a1476eb26e62d.json"}}, {"family": "Kraut", "given": "Simone", "initials": "S"}, {"family": "Hadzic", "given": "Stefan", "initials": "S", "orcid": "0000-0001-8459-2776", "researcher": {"href": "https://publications.scilifelab.se/researcher/b590035525b645b2bc39840c20ae1046.json"}}, {"family": "Vazqu\u00e9z-Li\u00e9banas", "given": "Elisa", "initials": "E"}, {"family": "Kojonazarov", "given": "Baktybek", "initials": "B"}, {"family": "Wu", "given": "Cheng-Yu", "initials": "CY", "orcid": "0000-0002-2788-8586", "researcher": {"href": "https://publications.scilifelab.se/researcher/2c92dcbb1a954fa289532f7ba63e6604.json"}}, {"family": "Veith", "given": "Christine", "initials": "C"}, {"family": "He", "given": "Liqun", "initials": "L"}, {"family": "Mermelekas", "given": "Georgios", "initials": "G"}, {"family": "Schermuly", "given": "Ralph Theo", "initials": "RT"}, {"family": "Weissmann", "given": "Norbert", "initials": "N", "orcid": "0000-0003-2675-3871", "researcher": {"href": "https://publications.scilifelab.se/researcher/56802e4ac4104944abd3953fb94d6f19.json"}}, {"family": "Betsholtz", "given": "Christer", "initials": "C", "orcid": "0000-0002-8494-971X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a00cfe9d521047f280978d84d7dcf1b3.json"}}, {"family": "Andrae", "given": "Johanna", "initials": "J", "orcid": "0000-0003-0700-4381", "researcher": {"href": "https://publications.scilifelab.se/researcher/99efed4c5e864d30a789d4a3f46c817d.json"}}], "type": "journal article", "published": "2020-04-01", "journal": {"title": "Am J Physiol Lung Cell Mol Physiol", "issn": "1522-1504", "volume": "318", "issue": "4", "pages": "L831-L843", "issn-l": null}, "abstract": "PDGF-A is a key contributor to lung development in mice. Its expression is needed for secondary septation of the alveoli and deletion of the gene leads to abnormally enlarged alveolar air spaces in mice. In humans, the same phenotype is the hallmark of bronchopulmonary dysplasia (BPD), a disease that affects premature babies and may have long lasting consequences in adulthood. So far, the knowledge regarding adult effects of developmental arrest in the lung is limited. This is attributable to few follow-up studies of BPD survivors and lack of good experimental models that could help predict the outcomes of this early age disease for the adult individual. In this study, we used the constitutive lung-specific Pdgfa deletion mouse model to analyze the consequences of developmental lung defects in adult mice. We assessed lung morphology, physiology, cellular content, ECM composition and proteomics data in mature mice, that perinatally exhibited lungs with a BPD-like morphology. Histological and physiological analyses both revealed that enlarged alveolar air spaces remained until adulthood, resulting in higher lung compliance and higher respiratory volume in knockout mice. Still, no or only small differences were seen in cellular, ECM and protein content when comparing knockout and control mice. Taken together, our results indicate that Pdgfa deletion-induced lung developmental arrest has consequences for the adult lung at the morphological and functional level. In addition, these mice can reach adulthood with a BPD-like phenotype, which makes them a robust model to further investigate the pathophysiological progression of the disease and test putative regenerative therapies.", "doi": "10.1152/ajplung.00295.2019", "pmid": "32186397", "labels": {"Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7191480"}], "notes": [], "created": "2022-03-29T13:35:47.408Z", "modified": "2022-03-29T13:35:47.650Z"}, {"entity": "publication", "iuid": "c415e1ad145e4e3980e7a96e3c492895", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c415e1ad145e4e3980e7a96e3c492895.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c415e1ad145e4e3980e7a96e3c492895"}}, "title": "Extensive Clonal Branching Shapes the Evolutionary History of High-Risk Pediatric Cancers.", "authors": [{"family": "Andersson", "given": "Natalie", "initials": "N"}, {"family": "Bakker", "given": "Bjorn", "initials": "B", "orcid": "0000-0003-3095-7287", "researcher": {"href": "https://publications.scilifelab.se/researcher/b2f6637d70ea487bbd752150140416dc.json"}}, {"family": "Karlsson", "given": "Jenny", "initials": "J"}, {"family": "Valind", "given": "Anders", "initials": "A"}, {"family": "Holmquist Mengelbier", "given": "Linda", "initials": "L", "orcid": "0000-0002-3632-2760", "researcher": {"href": "https://publications.scilifelab.se/researcher/d6729b3f10e84432839564c382473607.json"}}, {"family": "Spierings", "given": "Diana C J", "initials": "DCJ", "orcid": "0000-0001-8403-474X", "researcher": {"href": "https://publications.scilifelab.se/researcher/62825465dc084c7ebd10b71e274d5eb2.json"}}, {"family": "Foijer", "given": "Floris", "initials": "F"}, {"family": "Gisselsson", "given": "David", "initials": "D"}], "type": "journal article", "published": "2020-04-01", "journal": {"title": "Cancer Res.", "issn": "1538-7445", "volume": "80", "issue": "7", "pages": "1512-1523", "issn-l": "0008-5472"}, "abstract": "Darwinian evolution of tumor cells remains underexplored in childhood cancer. We here reconstruct the evolutionary histories of 56 pediatric primary tumors, including 24 neuroblastomas, 24 Wilms tumors, and 8 rhabdomyosarcomas. Whole-genome copy-number and whole-exome mutational profiling of multiple regions per tumor were performed, followed by clonal deconvolution to reconstruct a phylogenetic tree for each tumor. Overall, 88% of the tumors exhibited genetic variation among primary tumor regions. This variability typically emerged through collateral phylogenetic branching, leading to spatial variability in the distribution of more than 50% (96/173) of detected diagnostically informative genetic aberrations. Single-cell sequencing of 547 individual cancer cells from eight solid pediatric tumors confirmed branching evolution to be a fundamental underlying principle of genetic variation in all cases. Strikingly, cell-to-cell genetic diversity was almost twice as high in aggressive compared with clinically favorable tumors (median Simpson index of diversity 0.45 vs. 0.88; P = 0.029). Similarly, a comparison of multiregional sampling data from a total of 274 tumor regions showed that new phylogenetic branches emerge at a higher frequency per sample and carry a higher mutational load in high-risk than in low-risk tumors. Timelines based on spatial genetic variation showed that the mutations most influencing relapse risk occur at initiation of clonal expansion in neuroblastoma and rhabdomyosarcoma, whereas in Wilms tumor, they are late events. Thus, from an evolutionary standpoint, some high-risk childhood cancers are born bad, whereas others grow worse over time. SIGNIFICANCE: Different pediatric cancers with a high risk of relapse share a common generic pattern of extensively branching evolution of somatic mutations. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/7/1512/F1.large.jpg.", "doi": "10.1158/0008-5472.CAN-19-3468", "pmid": "32041836", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service"}, "xrefs": [{"db": "pii", "key": "0008-5472.CAN-19-3468"}], "notes": [], "created": "2020-07-08T13:05:37.152Z", "modified": "2021-11-10T12:52:26.783Z"}, {"entity": "publication", "iuid": "4e3cb3704b79480991034259edc854ea", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4e3cb3704b79480991034259edc854ea.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4e3cb3704b79480991034259edc854ea"}}, "title": "Effects of whole-grain wheat, rye, and lignan supplementation on cardiometabolic risk factors in men with metabolic syndrome: a randomized crossover trial.", "authors": [{"family": "Eriksen", "given": "Anne K", "initials": "AK", "orcid": "0000-0002-4535-3788", "researcher": {"href": "https://publications.scilifelab.se/researcher/dc9f2263b20b42cf96dc666317b5818e.json"}}, {"family": "Brunius", "given": "Carl", "initials": "C"}, {"family": "Mazidi", "given": "Mohsen", "initials": "M"}, {"family": "Hellstr\u00f6m", "given": "Per M", "initials": "PM"}, {"family": "Ris\u00e9rus", "given": "Ulf", "initials": "U"}, {"family": "Iversen", "given": "Kia N", "initials": "KN"}, {"family": "Fristedt", "given": "Rikard", "initials": "R"}, {"family": "Sun", "given": "Li", "initials": "L"}, {"family": "Huang", "given": "Yi", "initials": "Y"}, {"family": "N\u00f8rskov", "given": "Natalja P", "initials": "NP"}, {"family": "Knudsen", "given": "Knud Erik B", "initials": "KEB"}, {"family": "Kyr\u00f8", "given": "Cecilie", "initials": "C"}, {"family": "Olsen", "given": "Anja", "initials": "A", "orcid": "0000-0003-4788-503X", "researcher": {"href": "https://publications.scilifelab.se/researcher/1236514511b54a5b9e633248151957a4.json"}}, {"family": "Tj\u00f8nneland", "given": "Anne", "initials": "A", "orcid": "0000-0003-4385-2097", "researcher": {"href": "https://publications.scilifelab.se/researcher/de22a0e2f07d43e19f370599a051f239.json"}}, {"family": "Dicksved", "given": "Johan", "initials": "J"}, {"family": "Landberg", "given": "Rikard", "initials": "R"}], "type": "journal article", "published": "2020-04-01", "journal": {"title": "Am. J. Clin. Nutr.", "issn": "1938-3207", "volume": "111", "issue": "4", "pages": "864-876", "issn-l": "0002-9165"}, "abstract": "A whole-grain (WG)-rich diet has shown to have potential for both prevention and treatment of the metabolic syndrome (MetS), which is a cluster of risk factors that increase the risk of type 2 diabetes and cardiovascular disease. Different WGs may have different health effects. WG rye, in particular, may improve glucose homeostasis and blood lipids, possibly mediated through fermentable dietary fiber and lignans. Recent studies have also suggested a crucial role of the gut microbiota in response to WG.\n\nThe aim was to investigate WG rye, alone and with lignan supplements [secoisolariciresinol diglucoside (SDG)], and WG wheat diets on glucose tolerance [oral-glucose-tolerance test (OGTT)], other cardiometabolic outcomes, enterolignans, and microbiota composition. Moreover, we exploratively evaluated the role of gut microbiota enterotypes in response to intervention diets.\n\nForty men with MetS risk profile were randomly assigned to WG diets in an 8-wk crossover study. The rye diet was supplemented with 280 mg SDG at weeks 4-8. Effects of treatment were evaluated by mixed-effects modeling, and effects on microbiota composition and the role of gut microbiota as a predictor of response to treatment were analyzed by random forest plots.\n\nThe WG rye diet (\u00b1 SDG supplements) did not affect the OGTT compared with WG wheat. Total and LDL cholesterol were lowered (-0.06 and -0.09 mmol/L, respectively; P < 0.05) after WG rye compared with WG wheat after 4 wk but not after 8 wk. WG rye resulted in higher abundance of Bifidobacterium [fold-change (FC) = 2.58, P < 0.001] compared with baseline and lower abundance of Clostridium genus compared with WG wheat (FC = 0.54, P = 0.02). The explorative analyses suggest that baseline enterotype is associated with total and LDL-cholesterol response to diet.\n\nWG rye, alone or with SDG supplementation, compared with WG wheat did not affect glucose metabolism but caused transient LDL-cholesterol reduction. The effect of WG diets appeared to differ according to enterotype. This trial was registered at www.clinicaltrials.gov as NCT02987595.", "doi": "10.1093/ajcn/nqaa026", "pmid": "32097450", "labels": {"NGI Stockholm (Genomics Applications)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "5758012"}, {"db": "ClinicalTrials.gov", "key": "NCT02987595"}], "notes": [], "created": "2021-01-08T16:29:15.845Z", "modified": "2024-01-16T13:48:42.669Z"}, {"entity": "publication", "iuid": "f0d8698f1e574a76ae40262eb1688cc2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f0d8698f1e574a76ae40262eb1688cc2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f0d8698f1e574a76ae40262eb1688cc2"}}, "title": "Development of basic building blocks for cryo-EM: the emcore and emvis software libraries.", "authors": [{"family": "de la Rosa-Trev\u00edn", "given": "Jos\u00e9 Miguel", "initials": "JM", "orcid": "0000-0002-3320-1269", "researcher": {"href": "https://publications.scilifelab.se/researcher/b9c797d9907249f0bb608c1340ac6f5c.json"}}, {"family": "Hern\u00e1ndez Viga", "given": "Pedro Alberto", "initials": "PA"}, {"family": "Ot\u00f3n", "given": "Joaqu\u00edn", "initials": "J", "orcid": "0000-0002-2195-4730", "researcher": {"href": "https://publications.scilifelab.se/researcher/6e00da8089474e7d86c26014cab70f9d.json"}}, {"family": "Lindahl", "given": "Erik", "initials": "E", "orcid": "0000-0003-1333-5398", "researcher": {"href": "https://publications.scilifelab.se/researcher/51600cedcf044bdda0f677deaeaf9fad.json"}}], "type": "journal article", "published": "2020-04-01", "journal": {"title": "Acta Crystallogr D Struct Biol", "issn": "2059-7983", "issn-l": "2059-7983", "volume": "76", "issue": "Pt 4", "pages": "350-356"}, "abstract": "Image-processing software has always been an integral part of structure determination by cryogenic electron microscopy (cryo-EM). Recent advances in hardware and software are recognized as one of the key factors in the so-called cryo-EM resolution revolution. Increasing computational power has opened many possibilities to consider more demanding algorithms, which in turn allow more complex biological problems to be tackled. Moreover, data processing has become more accessible to many experimental groups, with computations that used to last for many days at supercomputing facilities now being performed in hours on personal workstations. All of these advances, together with the rapid expansion of the community, continue to pose challenges and new demands on the software-development side. In this article, the development of emcore and emvis, two basic software libraries for image manipulation and data visualization in cryo-EM, is presented. The main goal is to provide basic functionality organized in modular components that other developers can reuse to implement new algorithms or build graphical applications. An additional aim is to showcase the importance of following established practices in software engineering, with the hope that this could be a first step towards a more standardized way of developing and distributing software in the field.", "doi": "10.1107/S2059798320003769", "pmid": "32254059", "labels": {"Cryo-EM": "Technology development"}, "xrefs": [{"db": "pii", "key": "S2059798320003769"}, {"db": "pmc", "key": "PMC7137102"}], "notes": [], "created": "2020-09-17T13:00:31.770Z", "modified": "2023-12-04T10:07:08.601Z"}, {"entity": "publication", "iuid": "f4135a8deebe4537aedfb6f14b11712e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f4135a8deebe4537aedfb6f14b11712e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f4135a8deebe4537aedfb6f14b11712e"}}, "title": "The acute effect of metabolic cofactor supplementation: a potential therapeutic strategy against non-alcoholic fatty liver disease.", "authors": [{"family": "Zhang", "given": "Cheng", "initials": "C", "orcid": "0000-0002-3721-8586", "researcher": {"href": "https://publications.scilifelab.se/researcher/d1b9559ac41749fa91c4025108947e13.json"}}, {"family": "Bjornson", "given": "Elias", "initials": "E"}, {"family": "Arif", "given": "Muhammad", "initials": "M"}, {"family": "Tebani", "given": "Abdellah", "initials": "A", "orcid": "0000-0002-8901-2678", "researcher": {"href": "https://publications.scilifelab.se/researcher/cf47745ed3454f3c819cf6414f140ff0.json"}}, {"family": "Lovric", "given": "Alen", "initials": "A"}, {"family": "Benfeitas", "given": "Rui", "initials": "R", "orcid": "0000-0001-7972-0083", "researcher": {"href": "https://publications.scilifelab.se/researcher/9ca09f57bdc44e7fa33a472f04859a4d.json"}}, {"family": "Ozcan", "given": "Mehmet", "initials": "M", "orcid": "0000-0002-1222-2802", "researcher": {"href": "https://publications.scilifelab.se/researcher/480be47a6ccd4f9ebc66d718997a3462.json"}}, {"family": "Juszczak", "given": "Kajetan", "initials": "K"}, {"family": "Kim", "given": "Woonghee", "initials": "W"}, {"family": "Kim", "given": "Jung Tae", "initials": "JT"}, {"family": "Bidkhori", "given": "Gholamreza", "initials": "G"}, {"family": "St\u00e5hlman", "given": "Marcus", "initials": "M"}, {"family": "Bergh", "given": "Per-Olof", "initials": "PO", "orcid": "0000-0001-9993-6965", "researcher": {"href": "https://publications.scilifelab.se/researcher/28c1f37dc6cc4ed98c8e8eb1a621fa2c.json"}}, {"family": "Adiels", "given": "Martin", "initials": "M"}, {"family": "Turkez", "given": "Hasan", "initials": "H"}, {"family": "Taskinen", "given": "Marja-Riitta", "initials": "MR"}, {"family": "Bosley", "given": "Jim", "initials": "J"}, {"family": "Marschall", "given": "Hanns-Ulrich", "initials": "HU"}, {"family": "Nielsen", "given": "Jens", "initials": "J", "orcid": "0000-0002-9955-6003", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a596e289be4438a8a2653b1f25fea8b.json"}}, {"family": "Uhl\u00e9n", "given": "Mathias", "initials": "M", "orcid": "0000-0002-4858-8056", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff81da3cb0cf4262873b993a1b06798c.json"}}, {"family": "Bor\u00e9n", "given": "Jan", "initials": "J", "orcid": "0000-0003-0786-8091", "researcher": {"href": "https://publications.scilifelab.se/researcher/1e85f6d287ce4c60a7b35b287efb4f79.json"}}, {"family": "Mardinoglu", "given": "Adil", "initials": "A", "orcid": "0000-0002-4254-6090", "researcher": {"href": "https://publications.scilifelab.se/researcher/da756265658c4ed2a8911644583e07a3.json"}}], "type": "journal article", "published": "2020-04-00", "journal": {"title": "Mol. Syst. Biol.", "issn": "1744-4292", "volume": "16", "issue": "4", "pages": "e9495", "issn-l": "1744-4292"}, "abstract": "The prevalence of non-alcoholic fatty liver disease (NAFLD) continues to increase dramatically, and there is no approved medication for its treatment. Recently, we predicted the underlying molecular mechanisms involved in the progression of NAFLD using network analysis and identified metabolic cofactors that might be beneficial as supplements to decrease human liver fat. Here, we first assessed the tolerability of the combined metabolic cofactors including l-serine, N-acetyl-l-cysteine (NAC), nicotinamide riboside (NR), and l-carnitine by performing a 7-day rat toxicology study. Second, we performed a human calibration study by supplementing combined metabolic cofactors and a control study to study the kinetics of these metabolites in the plasma of healthy subjects with and without supplementation. We measured clinical parameters and observed no immediate side effects. Next, we generated plasma metabolomics and inflammatory protein markers data to reveal the acute changes associated with the supplementation of the metabolic cofactors. We also integrated metabolomics data using personalized genome-scale metabolic modeling and observed that such supplementation significantly affects the global human lipid, amino acid, and antioxidant metabolism. Finally, we predicted blood concentrations of these compounds during daily long-term supplementation by generating an ordinary differential equation model and liver concentrations of serine by generating a pharmacokinetic model and finally adjusted the doses of individual metabolic cofactors for future human clinical trials.", "doi": "10.15252/msb.209495", "pmid": "32337855", "labels": {"Affinity Proteomics Stockholm": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7184219"}], "notes": [], "created": "2020-12-10T16:30:05.091Z", "modified": "2024-01-16T13:48:42.677Z"}, {"entity": "publication", "iuid": "d300bb8cee014355a843f9e69d6dc248", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d300bb8cee014355a843f9e69d6dc248.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d300bb8cee014355a843f9e69d6dc248"}}, "title": "Substantial intrinsic variability in chemoradiosensitivity of newly established anaplastic thyroid cancer cell-lines.", "authors": [{"family": "Gretarsson", "given": "Sigurdur", "initials": "S"}, {"family": "Nygren", "given": "Alexander", "initials": "A"}, {"family": "Rosendahl", "given": "Ann H", "initials": "AH"}, {"family": "Mylona", "given": "Nektaria", "initials": "N"}, {"family": "Kjell\u00e9n", "given": "Elisabeth", "initials": "E"}, {"family": "Jin", "given": "Yuesheng", "initials": "Y"}, {"family": "Paulsson", "given": "Kajsa", "initials": "K", "orcid": "0000-0001-7950-222X", "researcher": {"href": "https://publications.scilifelab.se/researcher/2033b23811f1432c90ad860dd993e7a8.json"}}, {"family": "Borg", "given": "\u00c5ke", "initials": "\u00c5", "orcid": "0000-0002-5793-132X", "researcher": {"href": "https://publications.scilifelab.se/researcher/127501d4e0854d14a4120acee9042bb7.json"}}, {"family": "Brun", "given": "Eva", "initials": "E"}, {"family": "Tennvall", "given": "Jan", "initials": "J"}, {"family": "Bergenfelz", "given": "Anders", "initials": "A", "orcid": "0000-0002-8355-6025", "researcher": {"href": "https://publications.scilifelab.se/researcher/6b9e952341cc4341a034638a5a57edf4.json"}}, {"family": "Greiff", "given": "Lennart", "initials": "L"}, {"family": "Wennerberg", "given": "Johan", "initials": "J"}, {"family": "Ekblad", "given": "Lars", "initials": "L"}], "type": "journal article", "published": "2020-04-00", "journal": {"title": "Acta Otolaryngol.", "issn": "1651-2251", "volume": "140", "issue": "4", "pages": "337-343", "issn-l": "0001-6489"}, "abstract": "Background: Well characterized human cell lines are needed for preclinical treatment studies of anaplastic thyroid cancer (ATC).Aims/Objectives: The aim was to establish, verify and characterize a panel of ATC cell lines.Material and methods: Cell lines were established from ATC fine-needle aspiration biopsies and characterized genetically and functionally regarding treatment sensitivities.Results: Eight cell lines were established in vitro and the anaplastic thyroid origin was verified. Seven of the cell lines were also grown as xenografts. The cell lines harboured complex karyotypes with modal numbers in hyperdiploid to near-pentaploid range. Five were TP53 mutated and three carried the BRAFV600E mutation. None had rearrangements of RET. For doxorubicin, IC50 ranged from 0.42 to 46 nmol/L and for paclitaxel from 1.6 to 196 nmol/L. Radiation sensitivity varied between 2.6 and 6.3 Gy. Two of the BRAF mutated cell lines displayed high sensitivity to vemurafenib, while the third was similar to the wild-type ones.Conclusions and significance: We describe a series of new ATC cell lines demonstrating large heterogeneity in the response to cytostatic drugs and the BRAF inhibitor vemurafenib. The observations are relevant to future attempts to optimize treatment combinations for ATC.", "doi": "10.1080/00016489.2019.1704055", "pmid": "31922436", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [], "notes": [], "created": "2020-09-15T07:46:41.011Z", "modified": "2021-11-10T12:52:32.575Z"}, {"entity": "publication", "iuid": "7a1f534e1da2463ea333f1d2835a0499", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7a1f534e1da2463ea333f1d2835a0499.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7a1f534e1da2463ea333f1d2835a0499"}}, "title": "Simultaneous mass spectrometry imaging of multiple neuropeptides in the brain and alterations induced by experimental parkinsonism and L-DOPA therapy.", "authors": [{"family": "Hulme", "given": "Heather", "initials": "H", "orcid": "0000-0002-2987-7397", "researcher": {"href": "https://publications.scilifelab.se/researcher/232094e6f2fc49209ba0ad11b65a1421.json"}}, {"family": "Fridjonsdottir", "given": "Elva", "initials": "E"}, {"family": "Gunnarsdottir", "given": "Halla", "initials": "H"}, {"family": "Vallianatou", "given": "Theodosia", "initials": "T"}, {"family": "Zhang", "given": "Xiaoqun", "initials": "X"}, {"family": "Wadensten", "given": "Henrik", "initials": "H"}, {"family": "Shariatgorji", "given": "Reza", "initials": "R"}, {"family": "Nilsson", "given": "Anna", "initials": "A"}, {"family": "Bezard", "given": "Erwan", "initials": "E"}, {"family": "Svenningsson", "given": "Per", "initials": "P"}, {"family": "Andr\u00e9n", "given": "Per E", "initials": "PE", "orcid": "0000-0002-4062-7743", "researcher": {"href": "https://publications.scilifelab.se/researcher/64f6381de42949db8d30b56b526f3e26.json"}}], "type": "journal article", "published": "2020-04-00", "journal": {"title": "Neurobiol. Dis.", "issn": "1095-953X", "volume": "137", "issue": null, "pages": "104738", "issn-l": "0969-9961"}, "abstract": "Neuropeptides are important signalling molecules in the brain and alterations in their expression levels have been linked to neurological disorders such as Parkinson's disease. It is challenging to map neuropeptide changes across and within brain regions because of their low in vivo concentrations and complex post-translational processing. Consequently, the role of neuropeptides in Parkinson's disease is not well understood. Thus, we have developed and evaluated a method to image multiple neuropeptides simultaneously in both rat and primate brain tissue sections by matrix-assisted laser desorption/ionisation mass spectrometry imaging at high lateral resolution. Using a unilateral 6-hydroxydopamine rat model of Parkinson's disease, we imaged changes in enkephalins, dynorphins, tachykinins and neurotensin associated with the dopaminergic denervation and L-DOPA treatment in multiple brain regions. L-DOPA administration significantly affected neuropeptides in the globus pallidus, while neuropeptides in the caudate-putamen were mostly affected by dopamine depletion. Using high lateral resolution imaging, we observed an increase of neurotensin in the dorsal sub-region of the globus pallidus after dopamine depletion. This study highlights the capacity of mass spectrometry imaging to elucidate the dynamics of neuropeptide signalling during Parkinson's disease and its treatment.", "doi": "10.1016/j.nbd.2020.104738", "pmid": "31927144", "labels": {"Spatial Mass Spectrometry": "Technology development"}, "xrefs": [{"db": "pii", "key": "S0969-9961(20)30013-9"}], "notes": [], "created": "2020-01-24T09:26:04.976Z", "modified": "2021-12-03T11:53:06.743Z"}, {"entity": "publication", "iuid": "84851b50878d4f5b85ea8fb5174a680f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/84851b50878d4f5b85ea8fb5174a680f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/84851b50878d4f5b85ea8fb5174a680f"}}, "title": "Screening for autoantibody targets in post-vaccination narcolepsy using proteome arrays.", "authors": [{"family": "Lind", "given": "Alexander", "initials": "A", "orcid": "0000-0002-1473-5468", "researcher": {"href": "https://publications.scilifelab.se/researcher/e6124e404ef349dc8d687838cb8eaf92.json"}}, {"family": "Eriksson", "given": "Daniel", "initials": "D"}, {"family": "Akel", "given": "Omar", "initials": "O"}, {"family": "Ramelius", "given": "Anita", "initials": "A"}, {"family": "Palm", "given": "Lars", "initials": "L"}, {"family": "Lernmark", "given": "\u00c5ke", "initials": "\u00c5"}, {"family": "K\u00e4mpe", "given": "Olle", "initials": "O"}, {"family": "Elding Larsson", "given": "Helena", "initials": "H"}, {"family": "Landegren", "given": "Nils", "initials": "N"}], "type": "journal article", "published": "2020-04-00", "journal": {"volume": "91", "issn": "1365-3083", "issue": "4", "pages": "e12864", "title": "Scand. J. Immunol.", "issn-l": "0300-9475"}, "abstract": "Narcolepsy type 1 (NT1) is a chronic sleep disorder caused by a specific loss of hypocretin-producing neurons. The incidence of NT1 increased in Sweden, Finland and Norway following Pandemrix\u00ae-vaccination, initiated to prevent the 2009 influenza pandemic. The pathogenesis of NT1 is poorly understood, and causal links to vaccination are yet to be clarified. The strong association with Human leukocyte antigen (HLA) DQB1*06:02 suggests an autoimmune pathogenesis, but proposed autoantigens remain controversial. We used a two-step approach to identify autoantigens in patients that acquired NT1 after Pandemrix\u00ae-vaccination. Using arrays of more than 9000 full-length human proteins, we screened the sera of 10 patients and 24 healthy subjects for autoantibodies. Identified candidate antigens were expressed in vitro to enable validation studies with radiobinding assays (RBA). The validation cohort included NT1 patients (n = 39), their first-degree relatives (FDR) (n = 66), population controls (n = 188), and disease controls representing multiple sclerosis (n = 100) and FDR to type 1 diabetes patients (n = 41). Reactivity towards previously suggested NT1 autoantigen candidates including Tribbles homolog 2, Prostaglandin D2 receptor, Hypocretin receptor 2 and \u03b1-MSH/proopiomelanocortin was not replicated in the protein array screen. By comparing case to control signals, three novel candidate autoantigens were identified in the protein array screen; LOC401464, PARP3 and FAM63B. However, the RBA did not confirm elevated reactivity towards either of these proteins. In summary, three putative autoantigens in NT1 were identified by protein array screening. Autoantibodies against these candidates could not be verified with independent methods. Further studies are warranted to identify hypothetical autoantigens related to the pathogenesis of Pandemrix\u00ae-induced NT1.", "doi": "10.1111/sji.12864", "pmid": "32056243", "labels": {"Autoimmunity and Serology Profiling": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [], "notes": [], "created": "2020-02-21T15:13:34.020Z", "modified": "2024-01-16T13:48:42.689Z"}, {"entity": "publication", "iuid": "2b6302172b5c4073976116e40f945d60", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2b6302172b5c4073976116e40f945d60.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2b6302172b5c4073976116e40f945d60"}}, "title": "Polymerase IV Plays a Crucial Role in Pollen Development in Capsella.", "authors": [{"family": "Wang", "given": "Zhenxing", "initials": "Z", "orcid": "0000-0001-5102-7121", "researcher": {"href": "https://publications.scilifelab.se/researcher/4b6c9f88c65d4fbc94da6d7598102335.json"}}, {"family": "Butel", "given": "Nicolas", "initials": "N", "orcid": "0000-0003-2484-4980", "researcher": {"href": "https://publications.scilifelab.se/researcher/f05a8316c3504f84abcc8cc66e770879.json"}}, {"family": "Santos-Gonz\u00e1lez", "given": "Juan", "initials": "J", "orcid": "0000-0002-8712-9776", "researcher": {"href": "https://publications.scilifelab.se/researcher/d26cc8b837e64875aa2226cb9a8b8da3.json"}}, {"family": "Borges", "given": "Filipe", "initials": "F", "orcid": "0000-0002-7388-2118", "researcher": {"href": "https://publications.scilifelab.se/researcher/08f47b282fc04126bb3359ec05ba9d02.json"}}, {"family": "Yi", "given": "Jun", "initials": "J", "orcid": "0000-0001-5539-0016", "researcher": {"href": "https://publications.scilifelab.se/researcher/c3fd9fa6dfce4a76996f52f7a8611b87.json"}}, {"family": "Martienssen", "given": "Robert A", "initials": "RA", "orcid": "0000-0003-1285-9608", "researcher": {"href": "https://publications.scilifelab.se/researcher/d40eed1e991b4eb08d5756886f50da55.json"}}, {"family": "Martinez", "given": "German", "initials": "G", "orcid": "0000-0002-5215-0866", "researcher": {"href": "https://publications.scilifelab.se/researcher/591f629ea8ed44c2bd9cd417dcebd8bc.json"}}, {"family": "K\u00f6hler", "given": "Claudia", "initials": "C", "orcid": "0000-0002-2619-4857", "researcher": {"href": "https://publications.scilifelab.se/researcher/accd3f9307614c8ab67154dd5e50cdac.json"}}], "type": "journal article", "published": "2020-04-00", "journal": {"title": "Plant Cell", "issn": "1532-298X", "issn-l": "1040-4651", "volume": "32", "issue": "4", "pages": "950-966"}, "abstract": "In Arabidopsis (Arabidopsis thaliana), DNA-dependent RNA polymerase IV (Pol IV) is required for the formation of transposable element (TE)-derived small RNA transcripts. These transcripts are processed by DICER-LIKE3 into 24-nucleotide small interfering RNAs (siRNAs) that guide RNA-directed DNA methylation. In the pollen grain, Pol IV is also required for the accumulation of 21/22-nucleotide epigenetically activated siRNAs, which likely silence TEs via post-transcriptional mechanisms. Despite this proposed role of Pol IV, its loss of function in Arabidopsis does not cause a discernible pollen defect. Here, we show that the knockout of NRPD1, encoding the largest subunit of Pol IV, in the Brassicaceae species Capsella (Capsella rubella), caused postmeiotic arrest of pollen development at the microspore stage. As in Arabidopsis, all TE-derived siRNAs were depleted in Capsella nrpd1 microspores. In the wild-type background, the same TEs produced 21/22-nucleotide and 24-nucleotide siRNAs; these processes required Pol IV activity. Arrest of Capsella nrpd1 microspores was accompanied by the deregulation of genes targeted by Pol IV-dependent siRNAs. TEs were much closer to genes in Capsella compared with Arabidopsis, perhaps explaining the essential role of Pol IV in pollen development in Capsella. Our discovery that Pol IV is functionally required in Capsella microspores emphasizes the relevance of investigating different plant models.", "doi": "10.1105/tpc.19.00938", "pmid": "31988265", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "tpc.19.00938"}, {"db": "pmc", "key": "PMC7145478"}], "notes": [], "created": "2020-12-08T23:35:28.348Z", "modified": "2021-11-10T12:52:33.683Z"}, {"entity": "publication", "iuid": "f2317acce3bc4c839fb919d77f6e0a01", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f2317acce3bc4c839fb919d77f6e0a01.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f2317acce3bc4c839fb919d77f6e0a01"}}, "title": "Molecular characterization of a large unselected cohort of metastatic colorectal cancers in relation to primary tumor location, rare metastatic sites and prognosis.", "authors": [{"family": "Nunes", "given": "Lu\u00eds", "initials": "L", "orcid": "0000-0002-3391-1607", "researcher": {"href": "https://publications.scilifelab.se/researcher/9be3293494cd4efe9bab07504cc1fcd0.json"}}, {"family": "Aaseb\u00f8", "given": "Kristine", "initials": "K", "orcid": "0000-0003-3575-5588", "researcher": {"href": "https://publications.scilifelab.se/researcher/d615e45a5b3340a79d3bd16c921c2ce2.json"}}, {"family": "Mathot", "given": "Lucy", "initials": "L", "orcid": "0000-0002-2990-2038", "researcher": {"href": "https://publications.scilifelab.se/researcher/c9f3bfe35ddf41e5beb4312d3408a7ea.json"}}, {"family": "Ljungstr\u00f6m", "given": "Viktor", "initials": "V"}, {"family": "Edqvist", "given": "Per-Henrik", "initials": "PH"}, {"family": "Sundstr\u00f6m", "given": "Magnus", "initials": "M"}, {"family": "Dragomir", "given": "Anca", "initials": "A", "orcid": "0000-0003-2777-8114", "researcher": {"href": "https://publications.scilifelab.se/researcher/da4c734efcc240d589dc5c99a433d904.json"}}, {"family": "Pfeiffer", "given": "Per", "initials": "P"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Ponten", "given": "Fredrik", "initials": "F", "orcid": "0000-0003-0703-3940", "researcher": {"href": "https://publications.scilifelab.se/researcher/a8b56979a6c74891aa277fb28848b6ce.json"}}, {"family": "Mezheyeuski", "given": "Artur", "initials": "A", "orcid": "0000-0002-4394-2634", "researcher": {"href": "https://publications.scilifelab.se/researcher/dd907ed1df0441b99789d3e045c4d890.json"}}, {"family": "Sorbye", "given": "Halfdan", "initials": "H"}, {"family": "Sj\u00f6blom", "given": "Tobias", "initials": "T", "orcid": "0000-0001-6668-4140", "researcher": {"href": "https://publications.scilifelab.se/researcher/909f00a5bf6e465f9ff560b12bcd863a.json"}}, {"family": "Glimelius", "given": "Bengt", "initials": "B", "orcid": "0000-0002-5440-791X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e79e661083f49bf90cbbfc19670f404.json"}}], "type": "journal article", "published": "2020-04-00", "journal": {"title": "Acta Oncol", "issn": "1651-226X", "volume": "59", "issue": "4", "pages": "417-426", "issn-l": "0284-186X"}, "abstract": "Background: We have reported that BRAF V600E mutations and microsatellite instability-high (MSI-H) are more prevalent in a population-based cohort of metastatic colorectal cancer (mCRC) patients than has been reported from clinical trials or hospital-based patient groups. The aim was to explore if other mutations in mCRC differ in prevalence between these cohorts in relation to mismatch repair status and primary tumor location and if presence of bone or brain metastases is associated with any mutations.Material and methods: A population-based cohort of 798 mCRC patients from three regions in Scandinavia was used. Forty-four cancer related genes were investigated in a custom designed Ampliseq hotspot panel. Differences in survival were analyzed using the Kaplan-Meier estimator and the Cox regression analysis.Results: Determination of mutations was possible in 449/501 patients for 40/44 genes. Besides BRAF V600E, seen in 19% of the tumors, none of the other mutations appeared more prevalent than in trial cohorts. BRAF V600E and MSI-H, seen in 8%, were associated with poor prognosis as was right-sided primary tumor location (39%) when compared to left-sided and rectum together; however, in a multivariable regression, only the BRAF mutation retained its statistical significance. No other mutations were associated with poor prognosis. ERBB2 alterations were more common if bone metastases were present at diagnosis (17% vs. 4%, p = .011). No association was found for brain metastases. Fifty-two percent had an alteration that is treatable with an FDA-approved targeted therapy, chiefly by EGFR-inhibitor for RAS wild-type and a check-point inhibitor for MSI-H tumors.Conclusions: Right-sided tumor location, BRAF V600E mutations, but no other investigated mutation, and MSI-H are more commonly seen in an unselected cohort than is reported from clinical patient cohorts, likely because they indicate poor prognosis. Half of the patients have a tumor that is treatable with an already FDA-approved targeted drug for mCRC.", "doi": "10.1080/0284186X.2019.1711169", "pmid": "31924107", "labels": {"National Genomics Infrastructure": "Collaborative", "NGI Uppsala (Uppsala Genome Center)": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [], "notes": [], "created": "2020-02-11T10:07:57.408Z", "modified": "2024-01-16T13:48:42.696Z"}, {"entity": "publication", "iuid": "5706e39b31514be89be947515ceebdee", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5706e39b31514be89be947515ceebdee.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5706e39b31514be89be947515ceebdee"}}, "title": "Long-term application of Swedish sewage sludge on farmland does not cause clear changes in the soil bacterial resistome.", "authors": [{"family": "Rutgersson", "given": "Carolin", "initials": "C"}, {"family": "Ebmeyer", "given": "Stefan", "initials": "S"}, {"family": "Lassen", "given": "Simon Bo", "initials": "SB"}, {"family": "Karkman", "given": "Antti", "initials": "A"}, {"family": "Fick", "given": "Jerker", "initials": "J"}, {"family": "Kristiansson", "given": "Erik", "initials": "E"}, {"family": "Brandt", "given": "Kristian K", "initials": "KK"}, {"family": "Flach", "given": "Carl-Fredrik", "initials": "CF"}, {"family": "Larsson", "given": "D G Joakim", "initials": "DGJ"}], "type": "journal article", "published": "2020-04-00", "journal": {"title": "Environ Int", "issn": "1873-6750", "volume": "137", "issue": null, "pages": "105339", "issn-l": "0160-4120"}, "abstract": "The widespread practice of applying sewage sludge to arable land makes use of nutrients indispensable for crops and reduces the need for inorganic fertilizer, however this application also provides a potential route for human exposure to chemical contaminants and microbial pathogens in the sludge. A recent concern is that such practice could promote environmental selection and dissemination of antibiotic resistant bacteria or resistance genes. Understanding the risks of sludge amendment in relation to antibiotic resistance development is important for sustainable agriculture, waste treatment and infectious disease management. To assess such risks, we took advantage of an agricultural field trial in southern Sweden, where land used for growing different crops has been amended with sludge every four years since 1981. We sampled raw, semi-digested and digested and stored sludge together with soils from the experimental plots before and two weeks after the most recent amendment in 2017. Levels of selected antimicrobials and bioavailable metals were determined and microbial effects were evaluated using both culture-independent metagenome sequencing and conventional culturing. Antimicrobials or bioavailable metals (Cu and Zn) did not accumulate to levels of concern for environmental selection of antibiotic resistance, and no coherent signs, neither on short or long time scales, of enrichment of antibiotic-resistant bacteria or resistance genes were found in soils amended with digested and stored sewage sludge in doses up to 12 metric tons per hectare. Likewise, only very few and slight differences in microbial community composition were observed after sludge amendment. Taken together, the current study does not indicate risks of sludge amendment related to antibiotic resistance development under the given conditions. Extrapolations should however be done with care as sludge quality and application practices vary between regions. Hence, the antibiotic concentrations and resistance load of the sludge are likely to be higher in regions with larger antibiotic consumption and resistance burden than Sweden.", "doi": "10.1016/j.envint.2019.105339", "pmid": "32036119", "labels": {"NGI Stockholm (Genomics Applications)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service"}, "xrefs": [{"db": "pii", "key": "S0160-4120(19)31788-X"}], "notes": [], "created": "2021-01-08T16:29:11.107Z", "modified": "2021-11-10T12:52:35.828Z"}, {"entity": "publication", "iuid": "c83707e3be244e97b835f054f03476c1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c83707e3be244e97b835f054f03476c1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c83707e3be244e97b835f054f03476c1"}}, "title": "Genes and variants in hematopoiesis-related pathways are associated with gemcitabine/carboplatin-induced thrombocytopenia.", "authors": [{"family": "Bj\u00f6rn", "given": "Niclas", "initials": "N", "orcid": "0000-0001-6806-4527", "researcher": {"href": "https://publications.scilifelab.se/researcher/a39cecc1714f4331b08a47f1f1bbe7ac.json"}}, {"family": "Sigurgeirsson", "given": "Benjam\u00edn", "initials": "B"}, {"family": "Svedberg", "given": "Anna", "initials": "A"}, {"family": "Pradhananga", "given": "Sailendra", "initials": "S", "orcid": "0000-0002-0834-3169", "researcher": {"href": "https://publications.scilifelab.se/researcher/c1917cb059924a779ac38e3023778461.json"}}, {"family": "Brand\u00e9n", "given": "Eva", "initials": "E"}, {"family": "Koyi", "given": "Hirsh", "initials": "H", "orcid": "0000-0001-5797-7873", "researcher": {"href": "https://publications.scilifelab.se/researcher/020d1b7e7693495484dc85c4ba6f2adc.json"}}, {"family": "Lewensohn", "given": "Rolf", "initials": "R"}, {"family": "de Petris", "given": "Luigi", "initials": "L"}, {"family": "Apell\u00e1niz-Ruiz", "given": "Maria", "initials": "M"}, {"family": "Rodr\u00edguez-Antona", "given": "Cristina", "initials": "C"}, {"family": "Lundeberg", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4313-1601", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a4e6ca0f29b4ead8569e2729481c3e0.json"}}, {"family": "Gr\u00e9en", "given": "Henrik", "initials": "H"}], "type": "journal article", "published": "2020-04-00", "journal": {"volume": "20", "issn": "1473-1150", "issue": "2", "title": "Pharmacogenomics J.", "pages": "179-191", "issn-l": "1470-269X"}, "abstract": "Chemotherapy-induced myelosuppression, including thrombocytopenia, is a recurrent problem during cancer treatments that may require dose alterations or cessations that could affect the antitumor effect of the treatment. To identify genetic markers associated with treatment-induced thrombocytopenia, we whole-exome sequenced 215 non-small cell lung cancer patients homogeneously treated with gemcitabine/carboplatin. The decrease in platelets (defined as nadir/baseline) was used to assess treatment-induced thrombocytopenia. Association between germline genetic variants and thrombocytopenia was analyzed at single-nucleotide variant (SNV) (based on the optimal false discovery rate, the severity of predicted consequence, and effect), gene, and pathway levels. These analyses identified 130 SNVs/INDELs and 25 genes associated with thrombocytopenia (P-value < 0.002). Twenty-three SNVs were validated in an independent genome-wide association study (GWAS). The top associations include rs34491125 in JMJD1C (P-value = 9.07 \u00d7 10-5), the validated variants rs10491684 in DOCK8 (P-value = 1.95 \u00d7 10-4), rs6118 in SERPINA5 (P-value = 5.83 \u00d7 10-4), and rs5877 in SERPINC1 (P-value = 1.07 \u00d7 10-3), and the genes CAPZA2 (P-value = 4.03 \u00d7 10-4) and SERPINC1 (P-value = 1.55 \u00d7 10-3). The SNVs in the top-scoring pathway \"Factors involved in megakaryocyte development and platelet production\" (P-value = 3.34 \u00d7 10-4) were used to construct weighted genetic risk score (wGRS) and logistic regression models that predict thrombocytopenia. The wGRS predict which patients are at high or low toxicity risk levels, for CTCAE (odds ratio (OR) = 22.35, P-value = 1.55 \u00d7 10-8), and decrease (OR = 66.82, P-value = 5.92 \u00d7 10-9). The logistic regression models predict CTCAE grades 3-4 (receiver operator characteristics (ROC) area under the curve (AUC) = 0.79), and large decrease (ROC AUC = 0.86). We identified and validated genetic variations within hematopoiesis-related pathways that provide a solid foundation for future studies using genetic markers for predicting chemotherapy-induced thrombocytopenia and personalizing treatments.", "doi": "10.1038/s41397-019-0099-8", "pmid": "31616045", "labels": {"National Genomics Infrastructure": "Service", "Bioinformatics Support, Infrastructure and Training": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support and Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41397-019-0099-8"}], "notes": [], "created": "2019-12-02T16:50:30.268Z", "modified": "2021-11-10T12:52:36.985Z"}, {"entity": "publication", "iuid": "0da0ae4f148b4c269b2e050772b012bc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0da0ae4f148b4c269b2e050772b012bc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0da0ae4f148b4c269b2e050772b012bc"}}, "title": "Establishing Trypanosoma cruzi farnesyl pyrophosphate synthase as a viable target for biosensor driven fragment-based lead discovery.", "authors": [{"family": "Opassi", "given": "Giulia", "initials": "G"}, {"family": "Nordstr\u00f6m", "given": "Helena", "initials": "H"}, {"family": "Lundin", "given": "Arne", "initials": "A"}, {"family": "Napolitano", "given": "Valeria", "initials": "V"}, {"family": "Magari", "given": "Francesca", "initials": "F"}, {"family": "Dzus", "given": "Tom", "initials": "T"}, {"family": "Klebe", "given": "Gerhard", "initials": "G", "orcid": "0000-0003-0177-537X", "researcher": {"href": "https://publications.scilifelab.se/researcher/6afa0eddded142f2a16043d896012024.json"}}, {"family": "Danielson", "given": "U Helena", "initials": "UH", "orcid": "0000-0003-2728-0340", "researcher": {"href": "https://publications.scilifelab.se/researcher/b2bf7dffedf44237807c23718c72efa6.json"}}], "type": "journal article", "published": "2020-04-00", "journal": {"title": "Protein Sci.", "issn": "1469-896X", "volume": "29", "issue": "4", "pages": "991-1003", "issn-l": "0961-8368"}, "abstract": "Procedures for producing and exploring Trypanosoma cruzi farnesyl pyrophosphate synthase (tcFPPS) for surface plasmon resonance (SPR) biosensor-driven fragment-based discovery have been established. The method requires functional sensor surfaces with high sensitivity for extended times and appropriate controls. Initial problems with protein stability and lack of useful reference compounds motivated optimization of experimental procedures and conditions. The improved methods enabled the production of pure, folded and dimeric protein, and identified procedures for storage and handling. A new coupled enzymatic assay, using luciferase for detection of pyrophosphate, was developed and used to confirm that the purified enzyme was active after purification and storage. It also confirmed that sensor surfaces prepared with structurally intact protein was active. An SPR-biosensor assay for fragment library screening and hit confirmation was developed. A thermal shift assay was used in parallel. A library of 90 fragments was efficiently screened by both assays at a single concentration in the presence and absence of the catalytic cofactor Mg2+ . Hits were selected on the basis of response levels or \u0394T m > 1\u00b0C and selectivity for tcFPPS in the presence of Mg2+ . Characterization of hits by SPR showed that all had low affinities and the relationships between steady-state responses and concentrations were not sufficiently hyperbolic for determination of KD -values. Instead, ranking could be performed from the slope of the linear relationship at low concentrations. This pilot screen confirms that the procedures developed herein enables SPR-biosensor driven fragment-based discovery of leads targeting tcFPPS, despite the lack of a reference compound. SIGNIFICANCE STATEMENT: To enable the discovery of drugs, it is essential to have access to relevant forms of the target protein and valid biochemical methods for studying the protein and effects of compounds that may be evolved into drugs. We have established methods for the discovery of drugs for treatment of American Trypanosomiasis (Chagas disease), using farnesyl pyrophosphate synthase from Trypanosoma cruzi as a target.", "doi": "10.1002/pro.3834", "pmid": "31994261", "labels": {"Drug Discovery and Development": null}, "xrefs": [{"db": "pmc", "key": "PMC7096706"}], "notes": [], "created": "2020-12-04T23:38:48.809Z", "modified": "2025-10-17T13:05:08.047Z"}, {"entity": "publication", "iuid": "cde1f74c4f7c4f958deb3b63f5280f49", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cde1f74c4f7c4f958deb3b63f5280f49.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cde1f74c4f7c4f958deb3b63f5280f49"}}, "title": "Cell Cycle Profiling Reveals Protein Oscillation, Phosphorylation, and Localization Dynamics.", "authors": [{"family": "Herr", "given": "Patrick", "initials": "P", "orcid": "0000-0003-2945-966X", "researcher": {"href": "https://publications.scilifelab.se/researcher/ab7a8452d9464b48a74737f6615df015.json"}}, {"family": "Bostr\u00f6m", "given": "Johan", "initials": "J", "orcid": "0000-0001-5252-4023", "researcher": {"href": "https://publications.scilifelab.se/researcher/2af59464d2c74c27af7a43fb5d1a670e.json"}}, {"family": "Rullman", "given": "Eric", "initials": "E"}, {"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications.scilifelab.se/researcher/cf1e23d9748e4868a4b5e966e423b1a9.json"}}, {"family": "Vesterlund", "given": "Mattias", "initials": "M", "orcid": "0000-0001-9471-6592", "researcher": {"href": "https://publications.scilifelab.se/researcher/0942e438993b494db2a3db914852c808.json"}}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}, {"family": "Maddalo", "given": "Gianluca", "initials": "G"}, {"family": "Altun", "given": "Mikael", "initials": "M", "orcid": "0000-0002-6937-6124", "researcher": {"href": "https://publications.scilifelab.se/researcher/4317b773615e476694840e907b7b1a0c.json"}}], "type": "journal article", "published": "2020-04-00", "journal": {"title": "Mol. Cell Proteomics", "issn": "1535-9484", "volume": "19", "issue": "4", "pages": "608-623", "issn-l": "1535-9476"}, "abstract": "The cell cycle is a highly conserved process involving the coordinated separation of a single cell into two daughter cells. To relate transcriptional regulation across the cell cycle with oscillatory changes in protein abundance and activity, we carried out a proteome- and phospho-proteome-wide mass spectrometry profiling. We compared protein dynamics with gene transcription, revealing many transcriptionally regulated G2 mRNAs that only produce a protein shift after mitosis. Integration of CRISPR/Cas9 survivability studies further highlighted proteins essential for cell viability. Analyzing the dynamics of phosphorylation events and protein solubility dynamics over the cell cycle, we characterize predicted phospho-peptide motif distributions and predict cell cycle-dependent translocating proteins, as exemplified by the S-adenosylmethionine synthase MAT2A. Our study implicates this enzyme in translocating to the nucleus after the G1/S-checkpoint, which enables epigenetic histone methylation maintenance during DNA replication. Taken together, this data set provides a unique integrated resource with novel insights on cell cycle dynamics.", "doi": "10.1074/mcp.RA120.001938", "pmid": "32051232", "labels": {"Global Proteomics and Proteogenomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S1535-9476(20)35020-9"}, {"db": "pmc", "key": "PMC7124475"}], "notes": [], "created": "2021-01-12T18:12:04.346Z", "modified": "2021-11-10T12:52:39.295Z"}, {"entity": "publication", "iuid": "c6e37a25c32f49e39274af08facd008d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c6e37a25c32f49e39274af08facd008d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c6e37a25c32f49e39274af08facd008d"}}, "title": "ABCB1 single-nucleotide variants and survival in patients with glioblastoma treated with radiotherapy concomitant with temozolomide.", "authors": [{"family": "Malmstr\u00f6m", "given": "Annika", "initials": "A", "orcid": "0000-0001-8410-4939", "researcher": {"href": "https://publications.scilifelab.se/researcher/34a15d92ca7442dcaec76288815f724c.json"}}, {"family": "\u0141ysiak", "given": "Malgorzata", "initials": "M", "orcid": "0000-0002-0244-759X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a7f5d37e79764c31a5a0a421c34ed1a8.json"}}, {"family": "\u00c5kesson", "given": "Lisa", "initials": "L"}, {"family": "Jakobsen", "given": "Ingrid", "initials": "I"}, {"family": "Mudaisi", "given": "Munila", "initials": "M"}, {"family": "Milos", "given": "Peter", "initials": "P"}, {"family": "Hallbeck", "given": "Martin", "initials": "M", "orcid": "0000-0001-6716-0314", "researcher": {"href": "https://publications.scilifelab.se/researcher/17f7b361871045a1b1e3cdfec9ebe5ec.json"}}, {"family": "Fomichov", "given": "Victoria", "initials": "V"}, {"family": "Broholm", "given": "Helle", "initials": "H"}, {"family": "Grunnet", "given": "Kirsten", "initials": "K"}, {"family": "Poulsen", "given": "Hans Skovgaard", "initials": "HS"}, {"family": "Bratth\u00e4ll", "given": "Charlotte", "initials": "C"}, {"family": "Strandeus", "given": "Michael", "initials": "M"}, {"family": "Papagiannopoulou", "given": "Angeliki", "initials": "A"}, {"family": "Stenmark-Askmalm", "given": "Marie", "initials": "M"}, {"family": "Green", "given": "Henrik", "initials": "H"}, {"family": "S\u00f6derkvist", "given": "Peter", "initials": "P", "orcid": "0000-0001-9867-8706", "researcher": {"href": "https://publications.scilifelab.se/researcher/c1fc163b9a08421180f7f235af3897f4.json"}}], "type": "journal article", "published": "2020-04-00", "journal": {"title": "Pharmacogenomics J.", "issn": "1473-1150", "issn-l": "1470-269X", "volume": "20", "issue": "2", "pages": "213-219"}, "abstract": "Standard treatment for glioblastoma (GBM) patients is surgery and radiochemotherapy (RCT) with temozolomide (TMZ). TMZ is a substrate for ABCB1, a transmembrane drug transporter. It has been suggested that survival for GBM patients receiving TMZ is influenced by different single-nucleotide variants (SNV) of ABCB1. We therefore examined SNV:s of ABCB1, namely 1199G>A, 1236C>T, 2677G>T/A, and 3435C>T and correlated to survival for GBM patients receiving RCT. In a pilot cohort (97 patients) a significant correlation to survival was found for SNV 1199G>A, with median OS for variant G/G patients being 18.2 months versus 11.5 months for A/G (p = 0.012). We found no correlation to survival for the other SNV:s. We then expanded the cohort to 179 patients (expanded cohort) and also included a confirmatory cohort (49 patients) focusing on SNV 1199G>A. Median OS for G/G versus A/G plus A/A was 15.7 and 11.5 months, respectively (p = 0.085) for the expanded cohort and 13.8 versus 16.8 months (p = 0.19) for the confirmatory. In conclusion, in patients with GBM receiving RCT with TMZ, no correlation with survival was found for the SNV:s 1236C>T, 2677G>T/A, and 3435C>T of ABCB1. Although the SNV 1199G>A might have some impact, a clinically significant role could not be confirmed.", "doi": "10.1038/s41397-019-0107-z", "pmid": "31624332", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41397-019-0107-z"}], "notes": [], "created": "2020-12-11T13:38:43.422Z", "modified": "2024-01-16T13:48:42.714Z"}, {"entity": "publication", "iuid": "524e673c4b9048aea0126ac55a98c663", "links": {"self": {"href": "https://publications.scilifelab.se/publication/524e673c4b9048aea0126ac55a98c663.json"}, "display": {"href": "https://publications.scilifelab.se/publication/524e673c4b9048aea0126ac55a98c663"}}, "title": "A Multi-Omics Approach to Liver Diseases: Integration of Single Nuclei Transcriptomics with Proteomics and HiCap Bulk Data in Human Liver.", "authors": [{"family": "Cavalli", "given": "Marco", "initials": "M"}, {"family": "Diamanti", "given": "Klev", "initials": "K"}, {"family": "Pan", "given": "Gang", "initials": "G"}, {"family": "Spalinskas", "given": "Rapolas", "initials": "R"}, {"family": "Kumar", "given": "Chanchal", "initials": "C"}, {"family": "Deshmukh", "given": "Atul Shahaji", "initials": "AS"}, {"family": "Mann", "given": "Matthias", "initials": "M"}, {"family": "Sahl\u00e9n", "given": "Pelin", "initials": "P"}, {"family": "Komorowski", "given": "Jan", "initials": "J"}, {"family": "Wadelius", "given": "Claes", "initials": "C"}], "type": "journal article", "published": "2020-04-00", "journal": {"title": "OMICS", "issn": "1557-8100", "volume": "24", "issue": "4", "pages": "180-194", "issn-l": "1536-2310"}, "abstract": "The liver is the largest solid organ and a primary metabolic hub. In recent years, intact cell nuclei were used to perform single-nuclei RNA-seq (snRNA-seq) for tissues difficult to dissociate and for flash-frozen archived tissue samples to discover unknown and rare cell subpopulations. In this study, we performed snRNA-seq of a liver sample to identify subpopulations of cells based on nuclear transcriptomics. In 4282 single nuclei, we detected, on average, 1377 active genes and we identified seven major cell types. We integrated data from 94,286 distal interactions (p < 0.05) for 7682 promoters from a targeted chromosome conformation capture technique (HiCap) and mass spectrometry proteomics for the same liver sample. We observed a reasonable correlation between proteomics and in silico bulk snRNA-seq (r = 0.47) using tissue-independent gene-specific protein abundancy estimation factors. We specifically looked at genes of medical importance. The DPYD gene is involved in the pharmacogenetics of fluoropyrimidine toxicity and some of its variants are analyzed for clinical purposes. We identified a new putative polymorphic regulatory element, which may contribute to variation in toxicity. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and we investigated all known risk genes. We identified a complex regulatory landscape for the SLC2A2 gene with 16 candidate enhancers. Three of them harbor somatic motif breaking and other mutations in HCC in the Pan Cancer Analysis of Whole Genomes dataset and are candidates to contribute to malignancy. Our results highlight the potential of a multi-omics approach in the study of human diseases.", "doi": "10.1089/omi.2019.0215", "pmid": "32181701", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7185313"}], "notes": [], "created": "2020-11-16T09:10:16.494Z", "modified": "2024-01-16T13:48:42.722Z"}, {"entity": "publication", "iuid": "a34d9cdcb8744d77a97282ebb665da1a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a34d9cdcb8744d77a97282ebb665da1a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a34d9cdcb8744d77a97282ebb665da1a"}}, "title": "Transcriptome Profiling and Toxicity Following Long-Term, Low Dose Exposure of Human Lung Cells to Ni and NiO Nanoparticles-Comparison with NiCl2.", "authors": [{"family": "Gliga", "given": "Anda R", "initials": "AR"}, {"family": "Di Bucchianico", "given": "Sebastiano", "initials": "S", "orcid": "0000-0002-6396-892X", "researcher": {"href": "https://publications.scilifelab.se/researcher/22ab671e103c40038515391da27d859c.json"}}, {"family": "\u00c5kerlund", "given": "Emma", "initials": "E"}, {"family": "Karlsson", "given": "Hanna L", "initials": "HL"}], "type": "journal article", "published": "2020-03-31", "journal": {"title": "Nanomaterials (Basel)", "issn": "2079-4991", "volume": "10", "issue": "4", "pages": "649", "issn-l": "2079-4991"}, "abstract": "Production of nickel (Ni) and nickel oxide (NiO) nanoparticles (NPs) leads to a risk of exposure and subsequent health effects. Understanding the toxicological effects and underlying mechanisms using relevant in vitro methods is, therefore, needed. The aim of this study is to explore changes in gene expression using RNA sequencing following long term (six weeks) low dose (0.5 \u00b5g Ni/mL) exposure of human lung cells (BEAS-2B) to Ni and NiO NPs as well as soluble NiCl2. Genotoxicity and cell transformation as well as cellular dose of Ni are also analyzed. Exposure to NiCl2 resulted in the largest number of differentially expressed genes (197), despite limited uptake, suggesting a major role of extracellular receptors and downstream signaling. Gene expression changes for all Ni exposures included genes coding for calcium-binding proteins (S100A14 and S100A2) as well as TIMP3, CCND2, EPCAM, IL4R and DDIT4. Several top enriched pathways for NiCl2 were defined by upregulation of, e.g., interleukin-1A and -1B, as well as Vascular Endothelial Growth Factor A (VEGFA). All Ni exposures caused DNA strand breaks (comet assay), whereas no induction of micronuclei was observed. Taken together, this study provides an insight into Ni-induced toxicity and mechanisms occurring at lower and more realistic exposure levels.", "doi": "10.3390/nano10040649", "pmid": "32244462", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service"}, "xrefs": [{"db": "pii", "key": "nano10040649"}, {"db": "pmc", "key": "PMC7221965"}], "notes": [], "created": "2020-07-08T13:04:59.092Z", "modified": "2021-11-10T12:52:42.707Z"}, {"entity": "publication", "iuid": "ed38171ac9fb4267b06326f783d43541", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ed38171ac9fb4267b06326f783d43541.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ed38171ac9fb4267b06326f783d43541"}}, "title": "Mutations in COL1A1/A2 and CREB3L1 are associated with oligodontia in osteogenesis imperfecta.", "authors": [{"family": "Andersson", "given": "Kristofer", "initials": "K"}, {"family": "Malmgren", "given": "Barbro", "initials": "B"}, {"family": "\u00c5str\u00f6m", "given": "Eva", "initials": "E"}, {"family": "Nordgren", "given": "Ann", "initials": "A"}, {"family": "Taylan", "given": "Fulya", "initials": "F"}, {"family": "Dahll\u00f6f", "given": "G\u00f6ran", "initials": "G"}], "type": "journal article", "published": "2020-03-31", "journal": {"title": "Orphanet J Rare Dis", "issn": "1750-1172", "volume": "15", "issue": "1", "pages": "80", "issn-l": "1750-1172"}, "abstract": "Osteogenesis imperfecta (OI) is a heterogeneous connective tissue disorder characterized by an increased tendency for fractures throughout life. Autosomal dominant (AD) mutations in COL1A1 and COL1A2 are causative in approximately 85% of cases. In recent years, recessive variants in genes involved in collagen processing have been found. Hypodontia (< 6 missing permanent teeth) and oligodontia (\u2265 6 missing permanent teeth) have previously been reported in individuals with OI. The aim of the present cross-sectional study was to investigate whether children and adolescents with OI and oligodontia and hypodontia also present with variants in other genes with potential effects on tooth development. The cohort comprised 10 individuals (7.7-19.9 years of age) with known COL1A1/A2 variants who we clinically and radiographically examined and further genetically evaluated by whole-genome sequencing. All study participants were treated at the Astrid Lindgren Children's Hospital at Karolinska University Hospital, Stockholm (Sweden's national multidisciplinary pediatric OI team). We evaluated a panel of genes that were associated with nonsyndromic and syndromic hypodontia or oligodontia as well as that had been found to be involved in tooth development in animal models.\n\nWe detected a homozygous nonsense variant in CREB3L1, p.Tyr428*, c.1284C > A in one boy previously diagnosed with OI type III. COL1A1 and COL1A2 were the only two genes among 9 individuals which carried a pathogenic mutation. We found rare variants with unknown significance in several other genes related to tooth development.\n\nOur findings suggest that mutations in COL1A1, COL1A2, and CREB3L1 may cause hypodontia and oligodontia in OI. The findings cannot exclude additive effects from other modifying or interacting genes that may contribute to the severity of the expressed phenotype. Larger cohorts and further functional studies are needed.", "doi": "10.1186/s13023-020-01361-4", "pmid": "32234057", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s13023-020-01361-4"}, {"db": "pmc", "key": "PMC7110904"}], "notes": [], "created": "2020-07-08T13:04:37.345Z", "modified": "2021-11-10T12:52:44.175Z"}, {"entity": "publication", "iuid": "35ceb41b656a47a982d5b274b2ccd969", "links": {"self": {"href": "https://publications.scilifelab.se/publication/35ceb41b656a47a982d5b274b2ccd969.json"}, "display": {"href": "https://publications.scilifelab.se/publication/35ceb41b656a47a982d5b274b2ccd969"}}, "title": "Identification of cell surface markers and establishment of monolayer differentiation to retinal pigment epithelial cells.", "authors": [{"family": "Plaza Reyes", "given": "Alvaro", "initials": "A", "orcid": "0000-0003-1167-6316", "researcher": {"href": "https://publications.scilifelab.se/researcher/36f7ddaf16ac45bfad26c96f292f2072.json"}}, {"family": "Petrus-Reurer", "given": "Sandra", "initials": "S", "orcid": "0000-0002-7051-1741", "researcher": {"href": "https://publications.scilifelab.se/researcher/716f74c81a3240e5b612dab55e997267.json"}}, {"family": "Padrell S\u00e1nchez", "given": "Sara", "initials": "S"}, {"family": "Kumar", "given": "Pankaj", "initials": "P", "orcid": "0000-0002-8411-1634", "researcher": {"href": "https://publications.scilifelab.se/researcher/5e9109710e2e45009c332e257c3c498a.json"}}, {"family": "Douagi", "given": "Iyadh", "initials": "I", "orcid": "0000-0002-3221-8667", "researcher": {"href": "https://publications.scilifelab.se/researcher/5a19504ddb2544bca5aeab9abf885b13.json"}}, {"family": "Bartuma", "given": "Hammurabi", "initials": "H"}, {"family": "Aronsson", "given": "Monica", "initials": "M"}, {"family": "Westman", "given": "Sofie", "initials": "S"}, {"family": "Lardner", "given": "Emma", "initials": "E"}, {"family": "Andr\u00e9", "given": "Helder", "initials": "H", "orcid": "0000-0002-2926-2376", "researcher": {"href": "https://publications.scilifelab.se/researcher/5e7098d1d25b4f31a2a45d41ab11da2f.json"}}, {"family": "Falk", "given": "Anna", "initials": "A"}, {"family": "Nandrot", "given": "Emeline F", "initials": "EF", "orcid": "0000-0003-3087-078X", "researcher": {"href": "https://publications.scilifelab.se/researcher/ed12259fa5b24f04853b930077e50077.json"}}, {"family": "Kvanta", "given": "Anders", "initials": "A"}, {"family": "Lanner", "given": "Fredrik", "initials": "F", "orcid": "0000-0002-2771-7445", "researcher": {"href": "https://publications.scilifelab.se/researcher/ba53ce48a35d413eb86cd104488ce669.json"}}], "type": "journal article", "published": "2020-03-30", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "11", "issue": "1", "pages": "1609", "issn-l": "2041-1723"}, "abstract": "In vitro differentiation of human pluripotent stem cells into functional retinal pigment epithelial (RPE) cells provides a potentially unlimited source for cell based reparative therapy of age-related macular degeneration. Although the inherent pigmentation of the RPE cells have been useful to grossly evaluate differentiation efficiency and allowed manual isolation of pigmented structures, accurate quantification and automated isolation has been challenging. To address this issue, here we perform a comprehensive antibody screening and identify cell surface markers for RPE cells. We show that these markers can be used to isolate RPE cells during in vitro differentiation and to track, quantify and improve differentiation efficiency. Finally, these surface markers aided to develop a robust, direct and scalable monolayer differentiation protocol on human recombinant laminin-111 and -521 without the need for manual isolation.", "doi": "10.1038/s41467-020-15326-5", "pmid": "32231223", "labels": {"Eukaryotic Single Cell Genomics (ESCG)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-15326-5"}, {"db": "pmc", "key": "PMC7105463"}], "notes": [], "created": "2020-10-06T11:08:22.218Z", "modified": "2024-01-16T13:48:42.729Z"}, {"entity": "publication", "iuid": "3d27ad2c075348029d3f5ac0be8dd349", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3d27ad2c075348029d3f5ac0be8dd349.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3d27ad2c075348029d3f5ac0be8dd349"}}, "title": "Antimicrobial peptide and sequence variation along a latitudinal gradient in two anurans.", "authors": [{"family": "Cort\u00e1zar-Chinarro", "given": "Maria", "initials": "M"}, {"family": "Meyer-Lucht", "given": "Yvonne", "initials": "Y"}, {"family": "Van der Valk", "given": "Tom", "initials": "T"}, {"family": "Richter-Boix", "given": "Alex", "initials": "A"}, {"family": "Laurila", "given": "Anssi", "initials": "A"}, {"family": "H\u00f6glund", "given": "Jacob", "initials": "J"}], "type": "journal article", "published": "2020-03-30", "journal": {"title": "BMC Genet.", "issn": "1471-2156", "volume": "21", "issue": "1", "pages": "38", "issn-l": "1471-2156"}, "abstract": "While there is evidence of both purifying and balancing selection in immune defense genes, large-scale genetic diversity in antimicrobial peptides (AMPs), an important part of the innate immune system released from dermal glands in the skin, has remained uninvestigated. Here we describe genetic diversity at three AMP loci (Temporin, Brevinin and Palustrin) in two ranid frogs (Rana arvalis and R. temporaria) along a 2000 km latitudinal gradient. We amplified and sequenced part of the Acidic Propiece domain and the hypervariable Mature Peptide domain (~ 150-200 bp) in the three genes using Illumina Miseq and expected to find decreased AMP genetic variation towards the northern distribution limit of the species similarly to studies on MHC genetic patterns.\n\nWe found multiple loci for each AMP and relatively high gene diversity, but no clear pattern of geographic genetic structure along the latitudinal gradient. We found evidence of trans-specific polymorphism in the two species, indicating a common evolutionary origin of the alleles. Temporin and Brevinin did not form monophyletic clades suggesting that they belong to the same gene family. By implementing codon evolution models we found evidence of strong positive selection acting on the Mature Peptide. We also found evidence of diversifying selection as indicated by divergent allele frequencies among populations and high Theta k values.\n\nOur results suggest that AMPs are an important source of adaptive diversity, minimizing the chance of microorganisms developing resistance to individual peptides.", "doi": "10.1186/s12863-020-00839-1", "pmid": "32228443", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12863-020-00839-1"}, {"db": "pmc", "key": "PMC7106915"}], "notes": [], "created": "2020-07-03T05:23:05.872Z", "modified": "2024-01-16T13:48:42.737Z"}, {"entity": "publication", "iuid": "f4b79cf485ae4ae2b999a8ce542884b9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f4b79cf485ae4ae2b999a8ce542884b9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f4b79cf485ae4ae2b999a8ce542884b9"}}, "title": "Structural basis for the increased processivity of D-family DNA polymerases in complex with PCNA.", "authors": [{"family": "Madru", "given": "Cl\u00e9ment", "initials": "C"}, {"family": "Henneke", "given": "Ghislaine", "initials": "G"}, {"family": "Raia", "given": "Pierre", "initials": "P", "orcid": "0000-0003-3469-1922", "researcher": {"href": "https://publications.scilifelab.se/researcher/bdf3d3b11b384d52ba1bc00e7173b44b.json"}}, {"family": "Hugonneau-Beaufet", "given": "In\u00e8s", "initials": "I"}, {"family": "Pehau-Arnaudet", "given": "G\u00e9rard", "initials": "G"}, {"family": "England", "given": "Patrick", "initials": "P"}, {"family": "Lindahl", "given": "Erik", "initials": "E"}, {"family": "Delarue", "given": "Marc", "initials": "M"}, {"family": "Carroni", "given": "Marta", "initials": "M", "orcid": "0000-0002-7697-6427", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7f1bc1767024368abcb11a83184994a.json"}}, {"family": "Sauguet", "given": "Ludovic", "initials": "L"}], "type": "journal article", "published": "2020-03-27", "journal": {"volume": "11", "issn": "2041-1723", "issue": "1", "pages": "1591", "title": "Nat Commun", "issn-l": "2041-1723"}, "abstract": "Replicative DNA polymerases (DNAPs) have evolved the ability to copy the genome with high processivity and fidelity. In Eukarya and Archaea, the processivity of replicative DNAPs is greatly enhanced by its binding to the proliferative cell nuclear antigen (PCNA) that encircles the DNA. We determined the cryo-EM structure of the DNA-bound PolD-PCNA complex from Pyrococcus abyssi at 3.77 \u00c5. Using an integrative structural biology approach - combining cryo-EM, X-ray crystallography, protein-protein interaction measurements, and activity assays - we describe the molecular basis for the interaction and cooperativity between a replicative DNAP and PCNA. PolD recruits PCNA via a complex mechanism, which requires two different PIP-boxes. We infer that the second PIP-box, which is shared with the eukaryotic Pol\u03b1 replicative DNAP, plays a dual role in binding either PCNA or primase, and could be a master switch between an initiation and a processive phase during replication.", "doi": "10.1038/s41467-020-15392-9", "pmid": "32221299", "labels": {"Cryo-EM": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-15392-9"}, {"db": "pmc", "key": "PMC7101311"}], "notes": [], "created": "2020-04-16T10:31:32.697Z", "modified": "2021-11-10T12:52:47.618Z"}, {"entity": "publication", "iuid": "f514beaaa6a94ecaa2fe0b9657f4e58e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f514beaaa6a94ecaa2fe0b9657f4e58e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f514beaaa6a94ecaa2fe0b9657f4e58e"}}, "title": "Image-Based Morphological Profiling Identifies a Lysosomotropic, Iron-Sequestering Autophagy Inhibitor.", "authors": [{"family": "Laraia", "given": "Luca", "initials": "L", "orcid": "0000-0001-6692-3412", "researcher": {"href": "https://publications.scilifelab.se/researcher/83300aeac8834bd4aaf9061a85aaeb28.json"}}, {"family": "Garivet", "given": "Guillaume", "initials": "G"}, {"family": "Foley", "given": "Daniel J", "initials": "DJ"}, {"family": "Kaiser", "given": "Nadine", "initials": "N"}, {"family": "M\u00fcller", "given": "Sebastian", "initials": "S"}, {"family": "Zinken", "given": "Sarah", "initials": "S"}, {"family": "Pinkert", "given": "Thomas", "initials": "T"}, {"family": "Wilke", "given": "Julian", "initials": "J"}, {"family": "Corkery", "given": "Dale", "initials": "D"}, {"family": "Pahl", "given": "Axel", "initials": "A"}, {"family": "Sievers", "given": "Sonja", "initials": "S"}, {"family": "Janning", "given": "Petra", "initials": "P"}, {"family": "Arenz", "given": "Christoph", "initials": "C"}, {"family": "Wu", "given": "Yaowen", "initials": "Y"}, {"family": "Rodriguez", "given": "Rapha\u00ebl", "initials": "R"}, {"family": "Waldmann", "given": "Herbert", "initials": "H", "orcid": "0000-0002-9606-7247", "researcher": {"href": "https://publications.scilifelab.se/researcher/54124c0b6aaa4711ab41a2492264fd9a.json"}}], "type": "journal article", "published": "2020-03-27", "journal": {"volume": "59", "issn": "1521-3773", "issue": "14", "pages": "5721-5729", "title": "Angew. Chem. Int. Ed. Engl.", "issn-l": "1433-7851"}, "abstract": "Chemical proteomics is widely applied in small-molecule target identification. However, in general it does not identify non-protein small-molecule targets, and thus, alternative methods for target identification are in high demand. We report the discovery of the autophagy inhibitor autoquin and the identification of its molecular mode of action using image-based morphological profiling in the cell painting assay. A compound-induced fingerprint representing changes in 579 cellular parameters revealed that autoquin accumulates in lysosomes and inhibits their fusion with autophagosomes. In addition, autoquin sequesters Fe2+ in lysosomes, resulting in an increase of lysosomal reactive oxygen species and ultimately cell death. Such a mechanism of action would have been challenging to unravel by current methods. This work demonstrates the potential of the cell painting assay to deconvolute modes of action of small molecules, warranting wider application in chemical biology.", "doi": "10.1002/anie.201913712", "pmid": "31769920", "labels": {"Integrated Microscopy Technologies Ume\u00e5": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7154763"}], "notes": [], "created": "2020-02-12T14:10:14.267Z", "modified": "2021-11-10T12:52:48.688Z"}, {"entity": "publication", "iuid": "4637ca66aaac4fd0aab625b8c6355aad", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4637ca66aaac4fd0aab625b8c6355aad.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4637ca66aaac4fd0aab625b8c6355aad"}}, "title": "Deficits in Motor Performance, Neurotransmitters and Synaptic Plasticity in Elderly and Experimental Parkinsonian Mice Lacking GPR37.", "authors": [{"family": "Zhang", "given": "Xiaoqun", "initials": "X"}, {"family": "Mantas", "given": "Ioannis", "initials": "I"}, {"family": "Fridjonsdottir", "given": "Elva", "initials": "E"}, {"family": "Andr\u00e9n", "given": "Per E", "initials": "PE"}, {"family": "Chergui", "given": "Karima", "initials": "K"}, {"family": "Svenningsson", "given": "Per", "initials": "P"}], "type": "journal article", "published": "2020-03-27", "journal": {"title": "Front Aging Neurosci", "issn": "1663-4365", "volume": "12", "issue": null, "pages": "84", "issn-l": null}, "abstract": "Parkinson's disease (PD) etiology is attributed to aging and the progressive neurodegeneration of dopamine (DA) neurons of substantia nigra pars compacta (SNc). GPR37 is an orphan G-protein Coupled Receptor (GPCR) that is linked to the juvenile form of PD. In addition, misfolded GPR37 has been found in Lewy bodies. However, properly folded GPR37 found at the cell membrane appears to exert neuroprotection. In the present study we investigated the role of GPR37 in motor deficits due to aging or toxin-induced experimental parkinsonism. Elderly GPR37 knock out (KO) mice displayed hypolocomotion and worse fine movement performance compared to their WT counterparts. Striatal slice electrophysiology reveiled that GPR37 KO mice show profound decrease in long term potentiation (LTP) formation which is accompanied by an alteration in glutamate receptor subunit content. GPR37 KO animals exposed to intrastriatal 6-hydroxydopamine (6-OHDA) show poorer score in the behavioral cylinder test and more loss of the DA transporter (DAT) in striatum. The GPR37 KO striata exhibit a significant increase in GABA which is aggravated after DA depletion. Our data indicate that GPR37 KO mice have DA neuron deficit, enhanced striatal GABA levels and deficient corticostriatal LTP. They also respond stronger to 6-OHDA-induced neurotoxicity. Taken together, the data indicate that properly functional GPR37 may counteract aging processes and parkinsonism.", "doi": "10.3389/fnagi.2020.00084", "pmid": "32292338", "labels": {"Spatial Mass Spectrometry": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC7120535"}], "notes": [], "created": "2021-03-26T12:43:12.149Z", "modified": "2021-12-03T11:52:42.300Z"}, {"entity": "publication", "iuid": "e21fd1cb40c740a098c9804b828e3a5c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e21fd1cb40c740a098c9804b828e3a5c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e21fd1cb40c740a098c9804b828e3a5c"}}, "title": "Towards uterus tissue engineering: a comparative study of sheep uterus decellularisation.", "authors": [{"family": "Tiemann", "given": "T T", "initials": "TT"}, {"family": "Padma", "given": "A M", "initials": "AM"}, {"family": "Sehic", "given": "E", "initials": "E"}, {"family": "B\u00e4ckdahl", "given": "H", "initials": "H"}, {"family": "Oltean", "given": "M", "initials": "M"}, {"family": "Song", "given": "M J", "initials": "MJ"}, {"family": "Br\u00e4nnstr\u00f6m", "given": "M", "initials": "M"}, {"family": "Hellstr\u00f6m", "given": "M", "initials": "M"}], "type": "comparative study", "published": "2020-03-26", "journal": {"title": "Mol. Hum. Reprod.", "issn": "1460-2407", "volume": "26", "issue": "3", "pages": "167-178", "issn-l": "1360-9947"}, "abstract": "Uterus tissue engineering may dismantle limitations in current uterus transplantation protocols. A uterine biomaterial populated with patient-derived cells could potentially serve as a graft to circumvent complicated surgery of live donors, immunosuppressive medication and rejection episodes. Repeated uterine bioengineering studies on rodents have shown promising results using decellularised scaffolds to restore fertility in a partially impaired uterus and now mandate experiments on larger and more human-like animal models. The aim of the presented studies was therefore to establish adequate protocols for scaffold generation and prepare for future in vivo sheep uterus bioengineering experiments. Three decellularisation protocols were developed using vascular perfusion through the uterine artery of whole sheep uteri obtained from slaughterhouse material. Decellularisation solutions used were based on 0.5% sodium dodecyl sulphate (Protocol 1) or 2% sodium deoxycholate (Protocol 2) or with a sequential perfusion of 2% sodium deoxycholate and 1% Triton X-100 (Protocol 3). The scaffolds were examined by histology, extracellular matrix quantification, evaluation of mechanical properties and the ability to support foetal sheep stem cells after recellularisation. We showed that a sheep uterus can successfully be decellularised while maintaining a high integrity of the extracellular components. Uteri perfused with sodium deoxycholate (Protocol 2) were the most favourable treatment in our study based on quantifications. However, all scaffolds supported stem cells for 2 weeks in vitro and showed no cytotoxicity signs. Cells continued to express markers for proliferation and maintained their undifferentiated phenotype. Hence, this study reports three valuable decellularisation protocols for future in vivo sheep uterus bioengineering experiments.", "doi": "10.1093/molehr/gaaa009", "pmid": "31980817", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7103571"}, {"db": "pii", "key": "5715759"}], "notes": [], "created": "2023-02-16T08:09:57.817Z", "modified": "2023-02-16T08:09:57.820Z"}, {"entity": "publication", "iuid": "fa45dc8f027c484fab11c81fa878996a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/fa45dc8f027c484fab11c81fa878996a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/fa45dc8f027c484fab11c81fa878996a"}}, "title": "An mRNA-mRNA Interaction Couples Expression of a Virulence Factor and Its Chaperone in Listeria monocytogenes.", "authors": [{"family": "Ignatov", "given": "Dmitriy", "initials": "D"}, {"family": "Vaitkevicius", "given": "Karolis", "initials": "K"}, {"family": "Durand", "given": "Sylvain", "initials": "S"}, {"family": "Cahoon", "given": "Laty", "initials": "L"}, {"family": "Sandberg", "given": "Stefanie S", "initials": "SS"}, {"family": "Liu", "given": "Xijia", "initials": "X"}, {"family": "Kallipolitis", "given": "Birgitte H", "initials": "BH"}, {"family": "Ryd\u00e9n", "given": "Patrik", "initials": "P"}, {"family": "Freitag", "given": "Nancy", "initials": "N"}, {"family": "Condon", "given": "Ciar\u00e1n", "initials": "C"}, {"family": "Johansson", "given": "J\u00f6rgen", "initials": "J"}], "type": "journal article", "published": "2020-03-24", "journal": {"title": "Cell Rep", "issn": "2211-1247", "volume": "30", "issue": "12", "pages": "4027-4040.e7", "issn-l": null}, "abstract": "Bacterial pathogens often employ RNA regulatory elements located in the 5' untranslated regions (UTRs) to control gene expression. Using a comparative structural analysis, we examine the structure of 5' UTRs at a global scale in the pathogenic bacterium Listeria monocytogenes under different conditions. In addition to discovering an RNA thermoswitch and detecting simultaneous interaction of ribosomes and small RNAs with mRNA, we identify structural changes in the 5' UTR of an mRNA encoding the post-translocation chaperone PrsA2 during infection conditions. We demonstrate that the 5' UTR of the prsA2 mRNA base pairs with the 3' UTR of the full-length hly mRNA encoding listeriolysin O, thus preventing RNase J1-mediated degradation of the prsA2 transcript. Mutants lacking the hly-prsA2 interaction exhibit reduced virulence properties. This work highlights an additional level of RNA regulation, where the mRNA encoding a chaperone is stabilized by the mRNA encoding its substrate.", "doi": "10.1016/j.celrep.2020.03.006", "pmid": "32209466", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S2211-1247(20)30304-1"}], "notes": [], "created": "2020-12-07T16:27:00.041Z", "modified": "2024-01-16T13:48:42.745Z"}, {"entity": "publication", "iuid": "36235e9dc3c244d7a5646615de05fe18", "links": {"self": {"href": "https://publications.scilifelab.se/publication/36235e9dc3c244d7a5646615de05fe18.json"}, "display": {"href": "https://publications.scilifelab.se/publication/36235e9dc3c244d7a5646615de05fe18"}}, "title": "An atlas of human metabolism.", "authors": [{"family": "Robinson", "given": "Jonathan L", "initials": "JL", "orcid": "0000-0001-8567-5960", "researcher": {"href": "https://publications.scilifelab.se/researcher/b70b6d9b64fd45e882c4108aded013d4.json"}}, {"family": "Kocaba\u015f", "given": "P\u0131nar", "initials": "P", "orcid": "0000-0001-9788-2019", "researcher": {"href": "https://publications.scilifelab.se/researcher/c89eb03e619945a2a2058179b0d0e310.json"}}, {"family": "Wang", "given": "Hao", "initials": "H", "orcid": "0000-0001-7475-0136", "researcher": {"href": "https://publications.scilifelab.se/researcher/836b4fbf7ebd4f80abc84465c8f29a2e.json"}}, {"family": "Cholley", "given": "Pierre-Etienne", "initials": "PE"}, {"family": "Cook", "given": "Daniel", "initials": "D", "orcid": "0000-0001-5534-8600", "researcher": {"href": "https://publications.scilifelab.se/researcher/ad0b42774a1e4e0580dde05e95fcb1fc.json"}}, {"family": "Nilsson", "given": "Avlant", "initials": "A", "orcid": "0000-0002-9476-4516", "researcher": {"href": "https://publications.scilifelab.se/researcher/44da161dba604c9e803a4af303277083.json"}}, {"family": "Anton", "given": "Mihail", "initials": "M", "orcid": "0000-0002-7753-9042", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a28ecc2261e436ea5884ada5e512aed.json"}}, {"family": "Ferreira", "given": "Raphael", "initials": "R", "orcid": "0000-0001-9881-6232", "researcher": {"href": "https://publications.scilifelab.se/researcher/5e97f22759cd4e008d9b6473f52865e5.json"}}, {"family": "Domenzain", "given": "Iv\u00e1n", "initials": "I", "orcid": "0000-0002-5322-2040", "researcher": {"href": "https://publications.scilifelab.se/researcher/3793e87625584ee2a31301297263a12a.json"}}, {"family": "Billa", "given": "Virinchi", "initials": "V"}, {"family": "Limeta", "given": "Angelo", "initials": "A"}, {"family": "Hedin", "given": "Alex", "initials": "A", "orcid": "0000-0002-0829-2496", "researcher": {"href": "https://publications.scilifelab.se/researcher/88756d4d3b894ab288141af7b9c9b052.json"}}, {"family": "Gustafsson", "given": "Johan", "initials": "J", "orcid": "0000-0001-5072-2659", "researcher": {"href": "https://publications.scilifelab.se/researcher/bd5fda1ac79e49c185ba6f4dfcdff5fc.json"}}, {"family": "Kerkhoven", "given": "Eduard J", "initials": "EJ", "orcid": "0000-0002-3593-5792", "researcher": {"href": "https://publications.scilifelab.se/researcher/0df361f8014144e79479631fcbffad53.json"}}, {"family": "Svensson", "given": "L Thomas", "initials": "LT", "orcid": "0000-0002-9190-2979", "researcher": {"href": "https://publications.scilifelab.se/researcher/dc636683ece84dc4ac3e4d10df0c7a49.json"}}, {"family": "Palsson", "given": "Bernhard O", "initials": "BO", "orcid": "0000-0003-2357-6785", "researcher": {"href": "https://publications.scilifelab.se/researcher/b72eed29485a433cb85e260ee38dc894.json"}}, {"family": "Mardinoglu", "given": "Adil", "initials": "A", "orcid": "0000-0002-4254-6090", "researcher": {"href": "https://publications.scilifelab.se/researcher/da756265658c4ed2a8911644583e07a3.json"}}, {"family": "Hansson", "given": "Lena", "initials": "L"}, {"family": "Uhl\u00e9n", "given": "Mathias", "initials": "M", "orcid": "0000-0002-4858-8056", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff81da3cb0cf4262873b993a1b06798c.json"}}, {"family": "Nielsen", "given": "Jens", "initials": "J", "orcid": "0000-0002-9955-6003", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a596e289be4438a8a2653b1f25fea8b.json"}}], "type": "journal article", "published": "2020-03-24", "journal": {"title": "Sci Signal", "issn": "1937-9145", "issn-l": "1945-0877", "volume": "13", "issue": "624", "pages": null}, "abstract": "Genome-scale metabolic models (GEMs) are valuable tools to study metabolism and provide a scaffold for the integrative analysis of omics data. Researchers have developed increasingly comprehensive human GEMs, but the disconnect among different model sources and versions impedes further progress. We therefore integrated and extensively curated the most recent human metabolic models to construct a consensus GEM, Human1. We demonstrated the versatility of Human1 through the generation and analysis of cell- and tissue-specific models using transcriptomic, proteomic, and kinetic data. We also present an accompanying web portal, Metabolic Atlas (https://www.metabolicatlas.org/), which facilitates further exploration and visualization of Human1 content. Human1 was created using a version-controlled, open-source model development framework to enable community-driven curation and refinement. This framework allows Human1 to be an evolving shared resource for future studies of human health and disease.", "doi": "10.1126/scisignal.aaz1482", "pmid": "32209698", "labels": {"Systems Biology": "Technology development", "Bioinformatics Support, Infrastructure and Training": "Technology development", "Bioinformatics (NBIS)": "Technology development"}, "xrefs": [{"db": "pii", "key": "13/624/eaaz1482"}, {"db": "pmc", "key": "PMC7331181"}, {"db": "mid", "key": "NIHMS1590510"}], "notes": [], "created": "2020-12-10T11:11:44.807Z", "modified": "2021-11-10T12:52:52.282Z"}, {"entity": "publication", "iuid": "7964577bf0bb4f2f8925eb1bb6111278", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7964577bf0bb4f2f8925eb1bb6111278.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7964577bf0bb4f2f8925eb1bb6111278"}}, "title": "Marine Sediments Illuminate Chlamydiae Diversity and Evolution.", "authors": [{"family": "Dharamshi", "given": "Jennah E", "initials": "JE"}, {"family": "Tamarit", "given": "Daniel", "initials": "D"}, {"family": "Eme", "given": "Laura", "initials": "L"}, {"family": "Stairs", "given": "Courtney W", "initials": "CW"}, {"family": "Martijn", "given": "Joran", "initials": "J"}, {"family": "Homa", "given": "Felix", "initials": "F"}, {"family": "J\u00f8rgensen", "given": "Steffen L", "initials": "SL"}, {"family": "Spang", "given": "Anja", "initials": "A"}, {"family": "Ettema", "given": "Thijs J G", "initials": "TJG"}], "type": "journal article", "published": "2020-03-23", "journal": {"title": "Curr. Biol.", "issn": "1879-0445", "issn-l": "0960-9822", "volume": "30", "issue": "6", "pages": "1032-1048.e7"}, "abstract": "The bacterial phylum Chlamydiae is so far composed of obligate symbionts of eukaryotic hosts. Well known for Chlamydiaceae, pathogens of humans and other animals, Chlamydiae also include so-called environmental lineages that primarily infect microbial eukaryotes. Environmental surveys indicate that Chlamydiae are found in a wider range of environments than anticipated previously. However, the vast majority of this chlamydial diversity has been underexplored, biasing our current understanding of their biology, ecological importance, and evolution. Here, we report that previously undetected and active chlamydial lineages dominate microbial communities in deep anoxic marine sediments taken from the Arctic Mid-Ocean Ridge. Reaching relative abundances of up to 43% of the bacterial community, and a maximum diversity of 163 different species-level taxonomic units, these Chlamydiae represent important community members. Using genome-resolved metagenomics, we reconstructed 24 draft chlamydial genomes, expanding by over a third the known genomic diversity in this phylum. Phylogenomic analyses revealed several novel clades across the phylum, including a previously unknown sister lineage of the Chlamydiaceae, providing new insights into the origin of pathogenicity in this family. We were unable to identify putative eukaryotic hosts for these marine sediment chlamydiae, despite identifying genomic features that may be indicative of host-association. The high abundance and genomic diversity of Chlamydiae in these anoxic marine sediments indicate that some members could play an important, and thus far overlooked, ecological role in such environments and may indicate alternate lifestyle strategies.", "doi": "10.1016/j.cub.2020.02.016", "pmid": "32142706", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S0960-9822(20)30189-5"}, {"db": "figshare", "key": "10.6084/m9.figshare.11413008"}], "notes": [], "created": "2020-12-08T23:17:14.367Z", "modified": "2024-01-16T13:48:42.752Z"}, {"entity": "publication", "iuid": "a074964a79c24ad1b92ce498859976e4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a074964a79c24ad1b92ce498859976e4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a074964a79c24ad1b92ce498859976e4"}}, "title": "Molecular Profiling for Predictors of Radiosensitivity in Patients with Breast or Head-and-Neck Cancer.", "authors": [{"family": "Drobin", "given": "Kimi", "initials": "K"}, {"family": "Marczyk", "given": "Michal", "initials": "M", "orcid": "0000-0003-2508-5736", "researcher": {"href": "https://publications.scilifelab.se/researcher/f41817907c56448991e2c9e94f15da42.json"}}, {"family": "Halle", "given": "Martin", "initials": "M"}, {"family": "Danielsson", "given": "Daniel", "initials": "D", "orcid": "0000-0001-9407-2774", "researcher": {"href": "https://publications.scilifelab.se/researcher/45064e20ddfc4eadb626612584d8f95a.json"}}, {"family": "Papiez", "given": "Anna", "initials": "A", "orcid": "0000-0003-0179-1302", "researcher": {"href": "https://publications.scilifelab.se/researcher/f12e4932eb264f0096db641d0915e3b6.json"}}, {"family": "Sangsuwan", "given": "Traimate", "initials": "T", "orcid": "0000-0003-4051-8376", "researcher": {"href": "https://publications.scilifelab.se/researcher/7521353e59bd45f68393e2f85b2a978f.json"}}, {"family": "Bendes", "given": "Annika", "initials": "A", "orcid": "0000-0001-9329-2353", "researcher": {"href": "https://publications.scilifelab.se/researcher/50dffce4f4444dd8b5ff8f9294146a0b.json"}}, {"family": "Hong", "given": "Mun-Gwan", "initials": "MG", "orcid": "0000-0001-8603-8293", "researcher": {"href": "https://publications.scilifelab.se/researcher/5d66c199ece143a6ab15222d8b55e3ea.json"}}, {"family": "Qundos", "given": "Ulrika", "initials": "U"}, {"family": "Harms-Ringdahl", "given": "Mats", "initials": "M"}, {"family": "Wers\u00e4ll", "given": "Peter", "initials": "P"}, {"family": "Polanska", "given": "Joanna", "initials": "J", "orcid": "0000-0001-8004-9864", "researcher": {"href": "https://publications.scilifelab.se/researcher/329d4bcbf1e64ecca6bc2b3505cc8901.json"}}, {"family": "Schwenk", "given": "Jochen M", "initials": "JM", "orcid": "0000-0001-8141-8449", "researcher": {"href": "https://publications.scilifelab.se/researcher/aba5822711b246b397fffacb7ae403b3.json"}}, {"family": "Haghdoost", "given": "Siamak", "initials": "S", "orcid": "0000-0002-2867-4774", "researcher": {"href": "https://publications.scilifelab.se/researcher/e53acb351cb34d49924b840e1b2d2dc1.json"}}], "type": "journal article", "published": "2020-03-22", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "issn-l": "2072-6694", "volume": "12", "issue": "3", "pages": "753"}, "abstract": "Nearly half of all cancers are treated with radiotherapy alone or in combination with other treatments, where damage to normal tissues is a limiting factor for the treatment. Radiotherapy-induced adverse health effects, mostly of importance for cancer patients with long-term survival, may appear during or long time after finishing radiotherapy and depend on the patient's radiosensitivity. Currently, there is no assay available that can reliably predict the individual's response to radiotherapy. We profiled two study sets from breast (n = 29) and head-and-neck cancer patients (n = 74) that included radiosensitive patients and matched radioresistant controls.. We studied 55 single nucleotide polymorphisms (SNPs) in 33 genes by DNA genotyping and 130 circulating proteins by affinity-based plasma proteomics. In both study sets, we discovered several plasma proteins with the predictive power to find radiosensitive patients (adjusted p < 0.05) and validated the two most predictive proteins (THPO and STIM1) by sandwich immunoassays. By integrating genotypic and proteomic data into an analysis model, it was found that the proteins CHIT1, PDGFB, PNKD, RP2, SERPINC1, SLC4A, STIM1, and THPO, as well as the VEGFA gene variant rs69947, predicted radiosensitivity of our breast cancer (AUC = 0.76) and head-and-neck cancer (AUC = 0.89) patients. In conclusion, circulating proteins and a SNP variant of VEGFA suggest that processes such as vascular growth capacity, immune response, DNA repair and oxidative stress/hypoxia may be involved in an individual's risk of experiencing radiation-induced toxicity.", "doi": "10.3390/cancers12030753", "pmid": "32235817", "labels": {"Affinity Proteomics Stockholm": "Collaborative"}, "xrefs": [{"db": "pii", "key": "cancers12030753"}, {"db": "pmc", "key": "PMC7140105"}], "notes": [], "created": "2020-12-10T19:03:40.959Z", "modified": "2021-11-10T12:52:54.485Z"}, {"entity": "publication", "iuid": "5a7c87be5f77435b92107eb7304ec3e3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5a7c87be5f77435b92107eb7304ec3e3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5a7c87be5f77435b92107eb7304ec3e3"}}, "title": "Non-dopaminergic Alterations in Depression-Like FSL Rats in Experimental Parkinsonism and L-DOPA Responses.", "authors": [{"family": "Schintu", "given": "Nicoletta", "initials": "N"}, {"family": "Zhang", "given": "Xiaoqun", "initials": "X"}, {"family": "Stroth", "given": "Nikolas", "initials": "N"}, {"family": "Math\u00e9", "given": "Aleksander A", "initials": "AA"}, {"family": "Andr\u00e9n", "given": "Per E", "initials": "PE"}, {"family": "Svenningsson", "given": "Per", "initials": "P"}], "type": "journal article", "published": "2020-03-20", "journal": {"title": "Front Pharmacol", "issn": "1663-9812", "volume": "11", "issue": null, "pages": "304", "issn-l": "1663-9812"}, "abstract": "Depression is a common comorbid condition in Parkinson's disease (PD). Patients with depression have a two-fold increased risk to develop PD. Further, depression symptoms often precede motor symptoms in PD and are frequent at all stages of the disease. However, the influence of a depressive state on the responses to antiparkinson treatments is largely unknown. In this study, the genetically inbred depression-like flinders sensitive line (FSL) rats and control flinders resistant line (FRL) rats were studied in models of experimental parkinsonism. FSL rats showed a potentiated tremorgenic response to tacrine, a cholinesterase inhibitor used experimentally to induce 6 Hz resting tremor reminiscent of parkinsonian tremor. We also studied rats lesioned with 6-OHDA to induce hemiparkinsonism. No baseline differences in dopaminergic response to acute apomorphine or L-DOPA was found. However, following chronic treatment with L-DOPA, FRL rats developed sensitization of turning and abnormal involuntary movements (AIMs); these effects were counteracted by the anti-dyskinetic 5-HT1 A agonist/D2 partial agonist sarizotan. In contrast, FSL rats did not develop sensitization of turning and only minor AIMs in response to L-DOPA treatment. The roles of several non-dopamine systems underlying this discrepancy were studied. Unexpectedly, no differences of opioid neuropeptides or serotonin markers were found between FRL and FSL rats. The marked behavioral difference between the FRL and FSL rats was paralleled with the striatal expression of the established marker, c-fos, but also the GABAergic transporter (vGAT), and a hitherto unknown marker, tamalin, that is known to regulate mGluR5 receptor function and postsynaptic organization. This study demonstrates that behavioral and transcriptional responses of non-dopaminergic systems to experimental parkinsonism and L-DOPA are modified in a genetic rat model of depression.", "doi": "10.3389/fphar.2020.00304", "pmid": "32265703", "labels": {"Spatial Mass Spectrometry": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC7099513"}], "notes": [], "created": "2021-03-26T12:43:50.408Z", "modified": "2021-12-03T11:51:59.211Z"}, {"entity": "publication", "iuid": "406ca37ce27b4a10ac02f2696067f818", "links": {"self": {"href": "https://publications.scilifelab.se/publication/406ca37ce27b4a10ac02f2696067f818.json"}, "display": {"href": "https://publications.scilifelab.se/publication/406ca37ce27b4a10ac02f2696067f818"}}, "title": "Discovery of a novel integron-borne aminoglycoside resistance gene present in clinical pathogens by screening environmental bacterial communities.", "authors": [{"family": "B\u00f6hm", "given": "Maria-Elisabeth", "initials": "ME"}, {"family": "Razavi", "given": "Mohammad", "initials": "M"}, {"family": "Marathe", "given": "Nachiket P", "initials": "NP"}, {"family": "Flach", "given": "Carl-Fredrik", "initials": "CF"}, {"family": "Larsson", "given": "D G Joakim", "initials": "DGJ"}], "type": "journal article", "published": "2020-03-20", "journal": {"title": "Microbiome", "issn": "2049-2618", "volume": "8", "issue": "1", "pages": "41", "issn-l": "2049-2618"}, "abstract": "New antibiotic resistance determinants are generally discovered too late, long after they have irreversibly emerged in pathogens and spread widely. Early discovery of resistance genes, before or soon after their transfer to pathogens could allow more effective measures to monitor and reduce spread, and facilitate genetics-based diagnostics.\n\nWe modified a functional metagenomics approach followed by in silico filtering of known resistance genes to discover novel, mobilised resistance genes in class 1 integrons in wastewater-impacted environments. We identified an integron-borne gene cassette encoding a protein that conveys high-level resistance against aminoglycosides with a garosamine moiety when expressed in E. coli. The gene is named gar (garosamine-specific aminoglycoside resistance) after its specificity. It contains none of the functional domains of known aminoglycoside modifying enzymes, but bears characteristics of a kinase. By searching public databases, we found that the gene occurs in three sequenced, multi-resistant clinical isolates (two Pseudomonas aeruginosa and one Luteimonas sp.) from Italy and China, respectively, as well as in two food-borne Salmonella enterica isolates from the USA. In all cases, gar has escaped discovery until now.\n\nTo the best of our knowledge, this is the first time a novel resistance gene, present in clinical isolates, has been discovered by exploring the environmental microbiome. The gar gene has spread horizontally to different species on at least three continents, further limiting treatment options for bacterial infections. Its specificity to garosamine-containing aminoglycosides may reduce the usefulness of the newest semisynthetic aminoglycoside plazomicin, which is designed to avoid common aminoglycoside resistance mechanisms. Since the gene appears to be not yet common in the clinics, the data presented here enables early surveillance and maybe even mitigation of its spread.", "doi": "10.1186/s40168-020-00814-z", "pmid": "32197644", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s40168-020-00814-z"}, {"db": "pmc", "key": "PMC7085159"}], "notes": [], "created": "2020-03-24T07:52:19.291Z", "modified": "2021-11-10T12:52:56.851Z"}, {"entity": "publication", "iuid": "64b8dd1c84934112a999fca1e18e8ac2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/64b8dd1c84934112a999fca1e18e8ac2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/64b8dd1c84934112a999fca1e18e8ac2"}}, "title": "Specific functions for Mediator complex subunits from different modules in the transcriptional response of Arabidopsis thaliana to abiotic stress.", "authors": [{"family": "Crawford", "given": "Tim", "initials": "T"}, {"family": "Karamat", "given": "Fazeelat", "initials": "F"}, {"family": "Lehotai", "given": "N\u00f3ra", "initials": "N"}, {"family": "Rentoft", "given": "Matilda", "initials": "M"}, {"family": "Blomberg", "given": "Jeanette", "initials": "J"}, {"family": "Strand", "given": "\u00c5sa", "initials": "\u00c5"}, {"family": "Bj\u00f6rklund", "given": "Stefan", "initials": "S"}], "type": "journal article", "published": "2020-03-19", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "5073", "issn-l": "2045-2322"}, "abstract": "Adverse environmental conditions are detrimental to plant growth and development. Acclimation to abiotic stress conditions involves activation of signaling pathways which often results in changes in gene expression via networks of transcription factors (TFs). Mediator is a highly conserved co-regulator complex and an essential component of the transcriptional machinery in eukaryotes. Some Mediator subunits have been implicated in stress-responsive signaling pathways; however, much remains unknown regarding the role of plant Mediator in abiotic stress responses. Here, we use RNA-seq to analyze the transcriptional response of Arabidopsis thaliana to heat, cold and salt stress conditions. We identify a set of common abiotic stress regulons and describe the sequential and combinatorial nature of TFs involved in their transcriptional regulation. Furthermore, we identify stress-specific roles for the Mediator subunits MED9, MED16, MED18 and CDK8, and putative TFs connecting them to different stress signaling pathways. Our data also indicate different modes of action for subunits or modules of Mediator at the same gene loci, including a co-repressor function for MED16 prior to stress. These results illuminate a poorly understood but important player in the transcriptional response of plants to abiotic stress and identify target genes and mechanisms as a prelude to further biochemical characterization.", "doi": "10.1038/s41598-020-61758-w", "pmid": "32193425", "labels": {"Bioinformatics Support and Infrastructure": "Service", "Bioinformatics Support, Infrastructure and Training": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-61758-w"}, {"db": "pmc", "key": "PMC7081235"}], "notes": [], "created": "2021-07-02T06:44:54.540Z", "modified": "2021-11-10T12:52:58.039Z"}, {"entity": "publication", "iuid": "56f5b1c38609492dbef6474ced631d7c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/56f5b1c38609492dbef6474ced631d7c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/56f5b1c38609492dbef6474ced631d7c"}}, "title": "Analysis of the behaviour of confined molecules using 2H T1 nuclear magnetic relaxation dispersion", "authors": [{"family": "Shamshir", "given": "Adel", "initials": "A"}, {"family": "Sparrman", "given": "Tobias", "initials": "T", "orcid": "0000-0002-4442-6367", "researcher": {"href": "https://publications.scilifelab.se/researcher/f0d27dbd2f014795b1f7aa164d34bada.json"}}, {"family": "Westlund", "given": "Per Olof", "initials": "PO", "orcid": "0000-0002-9277-4534", "researcher": {"href": "https://publications.scilifelab.se/researcher/18985f1db0b64da48e7805cf918c58b3.json"}}], "type": "journal-article", "published": "2020-03-18", "journal": {"volume": "118", "issn": "0026-8976", "issue": "6", "pages": "e1645367", "title": "Molecular Physics", "issn-l": null}, "abstract": null, "doi": "10.1080/00268976.2019.1645367", "pmid": null, "labels": {"Swedish NMR Centre": "Collaborative"}, "xrefs": [], "notes": [], "created": "2019-11-22T14:24:58.271Z", "modified": "2025-10-17T13:03:57.035Z"}, {"entity": "publication", "iuid": "8e603d87758a42abbfab399d8aae90a8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8e603d87758a42abbfab399d8aae90a8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8e603d87758a42abbfab399d8aae90a8"}}, "title": "Newborn Screening for Presymptomatic Diagnosis of Complement and Phagocyte Deficiencies.", "authors": [{"family": "Dezfouli", "given": "Mahya", "initials": "M"}, {"family": "Bergstr\u00f6m", "given": "Sofia", "initials": "S"}, {"family": "Skattum", "given": "Lillemor", "initials": "L"}, {"family": "Abolhassani", "given": "Hassan", "initials": "H"}, {"family": "Neiman", "given": "Maja", "initials": "M"}, {"family": "Torabi-Rahvar", "given": "Monireh", "initials": "M"}, {"family": "Franco Jarava", "given": "Clara", "initials": "C"}, {"family": "Martin-Nalda", "given": "Andrea", "initials": "A"}, {"family": "Ferrer Balaguer", "given": "Juana M", "initials": "JM"}, {"family": "Slade", "given": "Charlotte A", "initials": "CA"}, {"family": "Roos", "given": "Anja", "initials": "A"}, {"family": "Fernandez Pereira", "given": "Luis M", "initials": "LM"}, {"family": "L\u00f3pez-Trascasa", "given": "Margarita", "initials": "M"}, {"family": "Gonzalez-Granado", "given": "Luis I", "initials": "LI"}, {"family": "Allende-Martinez", "given": "Luis M", "initials": "LM"}, {"family": "Mizuno", "given": "Yumi", "initials": "Y"}, {"family": "Yoshida", "given": "Yusuke", "initials": "Y"}, {"family": "Friman", "given": "Vanda", "initials": "V"}, {"family": "Lundgren", "given": "\u00c5sa", "initials": "\u00c5"}, {"family": "Aghamohammadi", "given": "Asghar", "initials": "A"}, {"family": "Rezaei", "given": "Nima", "initials": "N"}, {"family": "Hern\u00e1ndez-Gonzalez", "given": "Manuel", "initials": "M"}, {"family": "von D\u00f6beln", "given": "Ulrika", "initials": "U"}, {"family": "Truedsson", "given": "Lennart", "initials": "L"}, {"family": "Hara", "given": "Toshiro", "initials": "T"}, {"family": "Nonoyama", "given": "Shigeaki", "initials": "S"}, {"family": "Schwenk", "given": "Jochen M", "initials": "JM", "orcid": "0000-0001-8141-8449", "researcher": {"href": "https://publications.scilifelab.se/researcher/aba5822711b246b397fffacb7ae403b3.json"}}, {"family": "Nilsson", "given": "Peter", "initials": "P", "orcid": "0000-0002-4657-8532", "researcher": {"href": "https://publications.scilifelab.se/researcher/799bcf1cf8cf451296f4535dd4ca9dc0.json"}}, {"family": "Hammarstr\u00f6m", "given": "Lennart", "initials": "L"}], "type": "journal article", "published": "2020-03-17", "journal": {"title": "Front Immunol", "issn": "1664-3224", "issn-l": "1664-3224", "volume": "11", "issue": null, "pages": "455"}, "abstract": "The clinical outcomes of primary immunodeficiencies (PIDs) are greatly improved by accurate diagnosis early in life. However, it is not common to consider PIDs before the manifestation of severe clinical symptoms. Including PIDs in the nation-wide newborn screening programs will potentially improve survival and provide better disease management and preventive care in PID patients. This calls for the detection of disease biomarkers in blood and the use of dried blood spot samples, which is a part of routine newborn screening programs worldwide. Here, we developed a newborn screening method based on multiplex protein profiling for parallel diagnosis of 22 innate immunodeficiencies affecting the complement system and respiratory burst function in phagocytosis. The proposed method uses a small fraction of eluted blood from dried blood spots and is applicable for population-scale performance. The diagnosis method is validated through a retrospective screening of immunodeficient patient samples. This diagnostic approach can pave the way for an earlier, more comprehensive and accurate diagnosis of complement and phagocytic disorders, which ultimately lead to a healthy and active life for the PID patients.", "doi": "10.3389/fimmu.2020.00455", "pmid": "32256498", "labels": {"Affinity Proteomics Stockholm": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC7090021"}], "notes": [], "created": "2020-12-10T19:03:49.605Z", "modified": "2021-11-10T12:52:59.137Z"}, {"entity": "publication", "iuid": "2b5977da5b3448489e1540bbccf6f890", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2b5977da5b3448489e1540bbccf6f890.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2b5977da5b3448489e1540bbccf6f890"}}, "title": "Immune Profiling of Human Gut-Associated Lymphoid Tissue Identifies a Role for Isolated Lymphoid Follicles in Priming of Region-Specific Immunity.", "authors": [{"family": "Fenton", "given": "Thomas M", "initials": "TM"}, {"family": "J\u00f8rgensen", "given": "Peter B", "initials": "PB"}, {"family": "Niss", "given": "Kristoffer", "initials": "K"}, {"family": "Rubin", "given": "Samuel J S", "initials": "SJS"}, {"family": "M\u00f6rbe", "given": "Urs M", "initials": "UM"}, {"family": "Riis", "given": "Lene B", "initials": "LB"}, {"family": "Da Silva", "given": "Cl\u00e9ment", "initials": "C"}, {"family": "Plumb", "given": "Adam", "initials": "A"}, {"family": "Vandamme", "given": "Julien", "initials": "J"}, {"family": "Jakobsen", "given": "Henrik L", "initials": "HL"}, {"family": "Brunak", "given": "S\u00f8ren", "initials": "S"}, {"family": "Habtezion", "given": "Aida", "initials": "A"}, {"family": "Nielsen", "given": "Ole H", "initials": "OH"}, {"family": "Johansson-Lindbom", "given": "Bengt", "initials": "B"}, {"family": "Agace", "given": "William W", "initials": "WW"}], "type": "journal article", "published": "2020-03-17", "journal": {"title": "Immunity", "issn": "1097-4180", "volume": "52", "issue": "3", "pages": "557-570.e6", "issn-l": "1074-7613"}, "abstract": "The intestine contains some of the most diverse and complex immune compartments in the body. Here we describe a method for isolating human gut-associated lymphoid tissues (GALTs) that allows unprecedented profiling of the adaptive immune system in submucosal and mucosal isolated lymphoid follicles (SM-ILFs and M-ILFs, respectively) as well as in GALT-free intestinal lamina propria (LP). SM-ILF and M-ILF showed distinct patterns of distribution along the length of the intestine, were linked to the systemic circulation through MAdCAM-1+ high endothelial venules and efferent lymphatics, and had immune profiles consistent with immune-inductive sites. IgA sequencing analysis indicated that human ILFs are sites where intestinal adaptive immune responses are initiated in an anatomically restricted manner. Our findings position ILFs as key inductive hubs for regional immunity in the human intestine, and the methods presented will allow future assessment of these compartments in health and disease.", "doi": "10.1016/j.immuni.2020.02.001", "pmid": "32160523", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "S1074-7613(20)30072-8"}, {"db": "pmc", "key": "PMC7155934"}, {"db": "mid", "key": "NIHMS1568648"}], "notes": [], "created": "2020-07-03T05:24:52.368Z", "modified": "2021-11-10T12:53:00.374Z"}, {"entity": "publication", "iuid": "9467415b5d16477fbd0e52bb300c393b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9467415b5d16477fbd0e52bb300c393b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9467415b5d16477fbd0e52bb300c393b"}}, "title": "Effects of acute sleep loss on diurnal plasma dynamics of CNS health biomarkers in young men.", "authors": [{"family": "Benedict", "given": "Christian", "initials": "C", "orcid": "0000-0002-8911-4068", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe597b41566a4042a73152771650a0cc.json"}}, {"family": "Blennow", "given": "Kaj", "initials": "K"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H"}, {"family": "Cedernaes", "given": "Jonathan", "initials": "J", "orcid": "0000-0002-9052-8372", "researcher": {"href": "https://publications.scilifelab.se/researcher/46549a2cffc84c0b97e388ab09b977bc.json"}}], "type": "journal article", "published": "2020-03-17", "journal": {"title": "Neurology", "issn": "1526-632X", "issn-l": "0028-3878", "volume": "94", "issue": "11", "pages": "e1181-e1189"}, "abstract": "Disrupted sleep increases CSF levels of tau and \u03b2-amyloid (A\u03b2) and is associated with an increased risk of Alzheimer disease (AD). Our aim was to determine whether acute sleep loss alters diurnal profiles of plasma-based AD-associated biomarkers.\r\n\r\nIn a 2-condition crossover study, 15 healthy young men participated in 2 standardized sedentary in-laboratory conditions in randomized order: normal sleep vs overnight sleep loss. Plasma levels of total tau (t-tau), A\u03b240, A\u03b242, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were assessed using ultrasensitive single molecule array assays or ELISAs, in the fasted state in the evening prior to, and in the morning after, each intervention.\r\n\r\nIn response to sleep loss (+17.2%), compared with normal sleep (+1.8%), the evening to morning ratio was increased for t-tau (p = 0.035). No changes between the sleep conditions were seen for levels of A\u03b240, A\u03b242, NfL, or GFAP (all p > 0.10). The AD risk genotype rs4420638 did not significantly interact with sleep loss-related diurnal changes in plasma levels of A\u03b240 or A\u03b242 (p > 0.10). Plasma levels of A\u03b242 (-17.1%) and GFAP (-12.1%) exhibited an evening to morning decrease across conditions (p < 0.05).\r\n\r\nOur exploratory study suggests that acute sleep loss results in increased blood levels of t-tau. These changes provide further evidence that sleep loss may have detrimental effects on brain health even in younger individuals. Larger cohorts are warranted to delineate sleep vs circadian mechanisms, implications for long-term recurrent conditions (e.g., in shift workers), as well as interactions with other lifestyle and genetic factors.", "doi": "10.1212/WNL.0000000000008866", "pmid": "31915189", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "WNL.0000000000008866"}, {"db": "pmc", "key": "PMC7220231"}], "notes": [], "created": "2021-01-07T17:01:48.786Z", "modified": "2024-01-16T13:48:42.759Z"}, {"entity": "publication", "iuid": "927b0d312e3f4f6891a1798291eebe3e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/927b0d312e3f4f6891a1798291eebe3e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/927b0d312e3f4f6891a1798291eebe3e"}}, "title": "The application of differential scanning fluorimetry in exploring bisubstrate binding to protein arginine N-methyltransferase 1.", "authors": [{"family": "Brown", "given": "Jennifer I", "initials": "JI"}, {"family": "Page", "given": "Brent D G", "initials": "BDG"}, {"family": "Frankel", "given": "Adam", "initials": "A"}], "type": "journal article", "published": "2020-03-15", "journal": {"title": "Methods", "issn": "1095-9130", "volume": "175", "pages": "10-23", "issn-l": "1046-2023"}, "abstract": "Protein arginine N-methyltransferases (PRMTs) are a family of 9 enzymes that catalyze mono- or di-methylation of arginine residues using S-adenosyl-l-methionine (SAM). Arginine methylation is an important post-translational modification that can regulate the activity and structure of target proteins. Altered PRMT activity can lead to a variety of health issues including neurodevelopmental disease, autoimmune disorders, cancer, and cardiovascular disease. Thus, developing a robust mechanistic understanding of PRMT function may provide insight into these various disease states and enable the development of potential therapeutic agents. Although PRMTs have been studied for nearly two decades, a consensus regarding the mechanism of action for this class of enzymes has remained noticeably elusive. To address this shortcoming, differential scanning fluorimetry (DSF) was used to gain mechanistic insight into the order of PRMT substrate and cofactor binding. This methodology confirms that PRMT cofactor binding precedes target substrate binding and supports the use of DSF to study bisubstrate enzymatic reaction mechanisms.", "doi": "10.1016/j.ymeth.2019.11.004", "pmid": "31726226", "labels": {"Protein Science Facility (PSF)": "Service"}, "xrefs": [{"db": "pii", "key": "S1046-2023(19)30127-6"}], "notes": [], "created": "2024-04-03T14:14:14.851Z", "modified": "2024-04-03T14:14:14.856Z"}, {"entity": "publication", "iuid": "bbd542002470460c855f69cf5746f481", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bbd542002470460c855f69cf5746f481.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bbd542002470460c855f69cf5746f481"}}, "title": "Inherited DNA Repair Gene Mutations in Men with Lethal Prostate Cancer.", "authors": [{"family": "Rantapero", "given": "Tommi", "initials": "T"}, {"family": "Wahlfors", "given": "Tiina", "initials": "T"}, {"family": "K\u00e4hler", "given": "Anna", "initials": "A"}, {"family": "Hultman", "given": "Christina", "initials": "C"}, {"family": "Lindberg", "given": "Johan", "initials": "J"}, {"family": "Tammela", "given": "Teuvo Lj", "initials": "TL"}, {"family": "Nykter", "given": "Matti", "initials": "M"}, {"family": "Schleutker", "given": "Johanna", "initials": "J"}, {"family": "Wiklund", "given": "Fredrik", "initials": "F", "orcid": "0000-0002-4623-0544", "researcher": {"href": "https://publications.scilifelab.se/researcher/0650e45c937b4cf3bb36b60ae369c67e.json"}}], "type": "journal article", "published": "2020-03-14", "journal": {"title": "Genes", "issn": "2073-4425", "volume": "11", "issue": "3", "pages": "314", "issn-l": "2073-4425"}, "abstract": "Germline variants in DNA repair genes are associated with aggressive prostate cancer (PrCa). The aim of this study was to characterize germline variants in DNA repair genes associated with lethal PrCa in Finnish and Swedish populations. Whole-exome sequencing was performed for 122 lethal and 60 unselected PrCa cases. Among the lethal cases, a total of 16 potentially damaging protein-truncating variants in DNA repair genes were identified in 15 men (12.3%). Mutations were found in six genes with CHEK2 (4.1%) and ATM (3.3%) being most frequently mutated. Overall, the carrier rate of truncating variants in DNA repair genes among men with lethal PrCa significantly exceeded the carrier rate of 0% in 60 unselected PrCa cases (p = 0.030), and the prevalence of 1.6% (p < 0.001) and 5.4% (p = 0.040) in Swedish and Finnish population controls from the Exome Aggregation Consortium. No significant difference in carrier rate of potentially damaging nonsynonymous single nucleotide variants between lethal and unselected PrCa cases was observed (p = 0.123). We confirm that DNA repair genes are strongly associated with lethal PrCa in Sweden and Finland and highlight the importance of population-specific assessment of variants contributing to PrCa aggressiveness.", "doi": "10.3390/genes11030314", "pmid": "32183364", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "genes11030314"}, {"db": "pmc", "key": "PMC7140841"}], "notes": [], "created": "2020-07-08T13:04:09.131Z", "modified": "2024-01-16T13:48:42.766Z"}, {"entity": "publication", "iuid": "b666d402dd5343929e0fbb695aca0efe", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b666d402dd5343929e0fbb695aca0efe.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b666d402dd5343929e0fbb695aca0efe"}}, "title": "Ecosystem-wide metagenomic binning enables prediction of ecological niches from genomes.", "authors": [{"family": "Alneberg", "given": "Johannes", "initials": "J", "orcid": "0000-0002-2467-008X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a4d517d4f20046c08405f8aeecf4ad2a.json"}}, {"family": "Bennke", "given": "Christin", "initials": "C"}, {"family": "Beier", "given": "Sara", "initials": "S", "orcid": "0000-0003-3707-4487", "researcher": {"href": "https://publications.scilifelab.se/researcher/5358a1e162474073a69b08c32e7c5420.json"}}, {"family": "Bunse", "given": "Carina", "initials": "C"}, {"family": "Quince", "given": "Christopher", "initials": "C"}, {"family": "Ininbergs", "given": "Karolina", "initials": "K"}, {"family": "Riemann", "given": "Lasse", "initials": "L", "orcid": "0000-0001-9207-2543", "researcher": {"href": "https://publications.scilifelab.se/researcher/9fc561d1d5694c4c9fbc9a05dd741e17.json"}}, {"family": "Ekman", "given": "Martin", "initials": "M"}, {"family": "J\u00fcrgens", "given": "Klaus", "initials": "K"}, {"family": "Labrenz", "given": "Matthias", "initials": "M"}, {"family": "Pinhassi", "given": "Jarone", "initials": "J"}, {"family": "Andersson", "given": "Anders F", "initials": "AF", "orcid": "0000-0002-3627-6899", "researcher": {"href": "https://publications.scilifelab.se/researcher/caa76ee4438d4b4aad386ba8a90448c2.json"}}], "type": "journal article", "published": "2020-03-13", "journal": {"title": "Commun Biol", "issn": "2399-3642", "volume": "3", "issue": "1", "pages": "119", "issn-l": "2399-3642"}, "abstract": "The genome encodes the metabolic and functional capabilities of an organism and should be a major determinant of its ecological niche. Yet, it is unknown if the niche can be predicted directly from the genome. Here, we conduct metagenomic binning on 123 water samples spanning major environmental gradients of the Baltic Sea. The resulting 1961 metagenome-assembled genomes represent 352 species-level clusters that correspond to 1/3 of the metagenome sequences of the prokaryotic size-fraction. By using machine-learning, the placement of a genome cluster along various niche gradients (salinity level, depth, size-fraction) could be predicted based solely on its functional genes. The same approach predicted the genomes' placement in a virtual niche-space that captures the highest variation in distribution patterns. The predictions generally outperformed those inferred from phylogenetic information. Our study demonstrates a strong link between genome and ecological niche and provides a conceptual framework for predictive ecology based on genomic data.", "doi": "10.1038/s42003-020-0856-x", "pmid": "32170201", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s42003-020-0856-x"}, {"db": "pmc", "key": "PMC7070063"}], "notes": [], "created": "2020-07-08T13:04:08.349Z", "modified": "2024-01-16T13:48:42.773Z"}, {"entity": "publication", "iuid": "8afecd15e6b94e65880a25e3aa12d789", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8afecd15e6b94e65880a25e3aa12d789.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8afecd15e6b94e65880a25e3aa12d789"}}, "title": "Comparing the Performance of Microsatellites and RADseq in Population Genetic Studies: Analysis of Data for Pike (Esox lucius) and a Synthesis of Previous Studies.", "authors": [{"family": "Sunde", "given": "Johanna", "initials": "J"}, {"family": "Y\u0131ld\u0131r\u0131m", "given": "Ye\u015ferin", "initials": "Y"}, {"family": "Tibblin", "given": "Petter", "initials": "P"}, {"family": "Forsman", "given": "Anders", "initials": "A"}], "type": "journal article", "published": "2020-03-13", "journal": {"title": "Front Genet", "issn": "1664-8021", "volume": "11", "issue": null, "pages": "218", "issn-l": "1664-8021"}, "abstract": "Population genetic studies reveal biodiversity patterns and inform about drivers of evolutionary differentiation and adaptation, including gene flow, drift and selection. This can advance our understanding and aid decision making regarding management and conservation efforts. Microsatellites have long been used in population genetic studies. Thanks to the development of newer techniques, sequencing approaches such as restriction site associated DNA sequencing (RADseq) are on their way to replace microsatellites for some applications. However, the performance of these two marker types in population genetics have rarely been systematically compared. We utilized three neutrally and adaptively differentiated populations of anadromous pike (Esox lucius) to assess the relative performance of microsatellites and RADseq with respect to resolution and conclusiveness of estimates of population differentiation and genetic structure. To this end, the same set of individuals (N = 64) were genotyped with both RADseq and microsatellite markers. To assess effects of sample size, the same subset of 10 randomly chosen individuals from each population (N = 30 in total) were also genotyped with both methods. Comparisons of estimated genetic diversity and structure showed that both markers were able to uncover genetic structuring. The full RADseq dataset provided the clearest detection of the finer scaled genetic structuring, and the other three datasets (full and subset microsatellite, and subset RADseq) provided comparable results. A search for outlier loci performed on the full SNP dataset pointed to signs of selection potentially associated with salinity and temperature, exemplifying the utility of RADseq to inform about the importance of different environmental factors. To evaluate whether performance differences between the markers are general or context specific, the results of previous studies that have investigated population structure using both marker types were synthesized. The synthesis revealed that RADseq performed as well as, or better than microsatellites in detecting genetic structuring in the included studies. The differences in the ability to detect population structure, both in the present and the previous studies, are likely explained by the higher number of loci typically utilized in RADseq compared to microsatellite analysis, as increasing the number of markers will (regardless of the marker type) increase power and allow for clearer detection and higher resolution of genetic structure.", "doi": "10.3389/fgene.2020.00218", "pmid": "32231687", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7082332"}], "notes": [], "created": "2020-07-08T13:05:36.511Z", "modified": "2024-01-16T13:48:42.781Z"}, {"entity": "publication", "iuid": "d18a2001ca2a484ea1267aaed4906d19", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d18a2001ca2a484ea1267aaed4906d19.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d18a2001ca2a484ea1267aaed4906d19"}}, "title": "Exploiting loss of heterozygosity for allele-selective colorectal cancer chemotherapy.", "authors": [{"family": "Rendo", "given": "Veronica", "initials": "V", "orcid": "0000-0002-2983-4020", "researcher": {"href": "https://publications.scilifelab.se/researcher/7f3fe17dd4464af585b16916a88c34b7.json"}}, {"family": "Stoimenov", "given": "Ivaylo", "initials": "I"}, {"family": "Mateus", "given": "Andr\u00e9", "initials": "A", "orcid": "0000-0001-6870-0677", "researcher": {"href": "https://publications.scilifelab.se/researcher/d79942eca68f4b2d8c2e72cf258f1213.json"}}, {"family": "Sj\u00f6berg", "given": "Elin", "initials": "E"}, {"family": "Svensson", "given": "Richard", "initials": "R"}, {"family": "Gustavsson", "given": "Anna-Lena", "initials": "AL", "orcid": "0000-0003-4332-2336", "researcher": {"href": "https://publications.scilifelab.se/researcher/6b014ef7ea0d461b8e2ddb87506b1252.json"}}, {"family": "Johansson", "given": "Lars", "initials": "L"}, {"family": "Ng", "given": "Adrian", "initials": "A"}, {"family": "O\u02bcBrien", "given": "Casey", "initials": "C", "orcid": "0000-0002-6572-4881", "researcher": {"href": "https://publications.scilifelab.se/researcher/5782c9d8ce674fe8ad55eba0d514da54.json"}}, {"family": "Giannakis", "given": "Marios", "initials": "M"}, {"family": "Artursson", "given": "Per", "initials": "P", "orcid": "0000-0002-3708-7395", "researcher": {"href": "https://publications.scilifelab.se/researcher/31575936c2714e1eb2f35c12df9a65a8.json"}}, {"family": "Nygren", "given": "Peter", "initials": "P"}, {"family": "Cheong", "given": "Ian", "initials": "I"}, {"family": "Sj\u00f6blom", "given": "Tobias", "initials": "T", "orcid": "0000-0001-6668-4140", "researcher": {"href": "https://publications.scilifelab.se/researcher/909f00a5bf6e465f9ff560b12bcd863a.json"}}], "type": "journal article", "published": "2020-03-11", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "11", "issue": "1", "pages": "1308"}, "abstract": "Cancer chemotherapy targeting frequent loss of heterozygosity events is an attractive concept, since tumor cells may lack enzymatic activities present in normal constitutional cells. To find exploitable targets, we map prevalent genetic polymorphisms to protein structures and identify 45 nsSNVs (non-synonymous small nucleotide variations) near the catalytic sites of 17 enzymes frequently lost in cancer. For proof of concept, we select the gastrointestinal drug metabolic enzyme NAT2 at 8p22, which is frequently lost in colorectal cancers and has a common variant with 10-fold reduced activity. Small molecule screening results in a cytotoxic kinase inhibitor that impairs growth of cells with slow NAT2 and decreases the growth of tumors with slow NAT2 by half as compared to those with wild-type NAT2. Most of the patient-derived CRC cells expressing slow NAT2 also show sensitivity to 6-(4-aminophenyl)-N-(3,4,5-trimethoxyphenyl)pyrazin-2-amine (APA) treatment. These findings indicate that the therapeutic index of anti-cancer drugs can be altered by bystander mutations affecting drug metabolic genes.", "doi": "10.1038/s41467-020-15111-4", "pmid": "32161261", "labels": {"Bioinformatics Support for Computational Resources": "Service", "Chemical Biology Consortium Sweden": "Collaborative", "Drug Discovery and Development": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-15111-4"}, {"db": "pmc", "key": "PMC7066191"}], "notes": [], "created": "2020-03-17T11:11:47.766Z", "modified": "2025-10-17T13:05:08.058Z"}, {"entity": "publication", "iuid": "f89fbf236c224156aa48e89c92a6a48f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f89fbf236c224156aa48e89c92a6a48f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f89fbf236c224156aa48e89c92a6a48f"}}, "title": "Footprints of natural selection at the mannose-6-phosphate isomerase locus in barnacles.", "authors": [{"family": "Nunez", "given": "Joaquin C B", "initials": "JCB", "orcid": "0000-0002-3171-8918", "researcher": {"href": "https://publications.scilifelab.se/researcher/17eb1fe919d7471ebd0892307c72bea4.json"}}, {"family": "Flight", "given": "Patrick A", "initials": "PA"}, {"family": "Neil", "given": "Kimberly B", "initials": "KB"}, {"family": "Rong", "given": "Stephen", "initials": "S", "orcid": "0000-0002-6584-1391", "researcher": {"href": "https://publications.scilifelab.se/researcher/3944f25fb7a04a9b970260754505a28f.json"}}, {"family": "Eriksson", "given": "Leif A", "initials": "LA", "orcid": "0000-0001-5654-3109", "researcher": {"href": "https://publications.scilifelab.se/researcher/53b168b3ab17495783f874c427edd0c3.json"}}, {"family": "Ferranti", "given": "David A", "initials": "DA"}, {"family": "Rosenblad", "given": "Magnus Alm", "initials": "MA"}, {"family": "Blomberg", "given": "Anders", "initials": "A"}, {"family": "Rand", "given": "David M", "initials": "DM", "orcid": "0000-0001-6817-3459", "researcher": {"href": "https://publications.scilifelab.se/researcher/668b164c47974d5d8f733551d4d2dc2f.json"}}], "type": "journal article", "published": "2020-03-10", "journal": {"title": "Proc. Natl. Acad. Sci. U.S.A.", "issn": "1091-6490", "volume": "117", "issue": "10", "pages": "5376-5385", "issn-l": "0027-8424"}, "abstract": "The mannose-6-phosphate isomerase (Mpi) locus in Semibalanus balanoides has been studied as a candidate gene for balancing selection for more than two decades. Previous work has shown that Mpi allozyme genotypes (fast and slow) have different frequencies across Atlantic intertidal zones due to selection on postsettlement survival (i.e., allele zonation). We present the complete gene sequence of the Mpi locus and quantify nucleotide polymorphism in S. balanoides, as well as divergence to its sister taxon Semibalanus cariosus We show that the slow allozyme contains a derived charge-altering amino acid polymorphism, and both allozyme classes correspond to two haplogroups with multiple internal haplotypes. The locus shows several footprints of balancing selection around the fast/slow site: an enrichment of positive Tajima's D for nonsynonymous mutations, an excess of polymorphism, and a spike in the levels of silent polymorphism relative to silent divergence, as well as a site frequency spectrum enriched for midfrequency mutations. We observe other departures from neutrality across the locus in both coding and noncoding regions. These include a nonsynonymous trans-species polymorphism and a recent mutation under selection within the fast haplogroup. The latter suggests ongoing allelic replacement of functionally relevant amino acid variants. Moreover, predicted models of Mpi protein structure provide insight into the functional significance of the putatively selected amino acid polymorphisms. While footprints of selection are widespread across the range of S. balanoides, our data show that intertidal zonation patterns are variable across both spatial and temporal scales. These data provide further evidence for heterogeneous selection on Mpi.", "doi": "10.1073/pnas.1918232117", "pmid": "32098846", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "1918232117"}, {"db": "pmc", "key": "PMC7071928"}, {"db": "GENBANK", "key": "MK955540"}, {"db": "GENBANK", "key": "MK955547"}, {"db": "GENBANK", "key": "MK955548"}, {"db": "GENBANK", "key": "MK955609"}, {"db": "GENBANK", "key": "MK955610"}, {"db": "GENBANK", "key": "MK955671"}, {"db": "GENBANK", "key": "MK953001"}, {"db": "GENBANK", "key": "MK953005"}], "notes": [], "created": "2020-02-27T12:43:12.731Z", "modified": "2024-01-16T13:48:42.795Z"}, {"entity": "publication", "iuid": "6ef6a5481f8043e3a6bd28a7ef84d080", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6ef6a5481f8043e3a6bd28a7ef84d080.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6ef6a5481f8043e3a6bd28a7ef84d080"}}, "title": "Uncovering diversity and metabolic spectrum of animals in dead zone sediments.", "authors": [{"family": "Broman", "given": "Elias", "initials": "E", "orcid": "0000-0001-9005-5168", "researcher": {"href": "https://publications.scilifelab.se/researcher/63826da04a1f4f80bc3229df12bac9b7.json"}}, {"family": "Bonaglia", "given": "Stefano", "initials": "S", "orcid": "0000-0003-4366-0677", "researcher": {"href": "https://publications.scilifelab.se/researcher/c02dd99f9fd14dd89d5c231260806720.json"}}, {"family": "Holovachov", "given": "Oleksandr", "initials": "O", "orcid": "0000-0002-4285-0754", "researcher": {"href": "https://publications.scilifelab.se/researcher/7887fd76b35c47aaa67ac8ab7a1d07d5.json"}}, {"family": "Marzocchi", "given": "Ugo", "initials": "U", "orcid": "0000-0002-4746-9944", "researcher": {"href": "https://publications.scilifelab.se/researcher/85d1ad4b2b3e48db9cc591f4574cb848.json"}}, {"family": "Hall", "given": "Per O J", "initials": "POJ"}, {"family": "Nascimento", "given": "Francisco J A", "initials": "FJA", "orcid": "0000-0003-3722-1360", "researcher": {"href": "https://publications.scilifelab.se/researcher/5c2cfb0d7a614432b9dfdfcfa3fc4644.json"}}], "type": "journal article", "published": "2020-03-06", "journal": {"title": "Commun Biol", "issn": "2399-3642", "volume": "3", "issue": "1", "pages": "106", "issn-l": "2399-3642"}, "abstract": "Ocean deoxygenation driven by global warming and eutrophication is a primary concern for marine life. Resistant animals may be present in dead zone sediments, however there is lack of information on their diversity and metabolism. Here we combined geochemistry, microscopy, and RNA-seq for estimating taxonomy and functionality of micrometazoans along an oxygen gradient in the largest dead zone in the world. Nematodes are metabolically active at oxygen concentrations below 1.8 \u00b5mol L-1, and their diversity and community structure are different between low oxygen areas. This is likely due to toxic hydrogen sulfide and its potential to be oxidized by oxygen or nitrate. Zooplankton resting stages dominate the metazoan community, and these populations possibly use cytochrome c oxidase as an oxygen sensor to exit dormancy. Our study sheds light on mechanisms of animal adaptation to extreme environments. These biological resources can be essential for recolonization of dead zones when oxygen conditions improve.", "doi": "10.1038/s42003-020-0822-7", "pmid": "32144383", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s42003-020-0822-7"}, {"db": "pmc", "key": "PMC7060179"}], "notes": [], "created": "2020-07-08T13:05:16.537Z", "modified": "2024-01-16T13:48:42.803Z"}, {"entity": "publication", "iuid": "2f4e1e715e8a4083a08bb02c679a5334", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2f4e1e715e8a4083a08bb02c679a5334.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2f4e1e715e8a4083a08bb02c679a5334"}}, "title": "Ribonucleotide reductase inhibitors suppress SAMHD1 ara-CTPase activity enhancing cytarabine efficacy.", "authors": [{"family": "Rudd", "given": "Sean G", "initials": "SG", "orcid": "0000-0002-4368-3855", "researcher": {"href": "https://publications.scilifelab.se/researcher/cf1e23d9748e4868a4b5e966e423b1a9.json"}}, {"family": "Tsesmetzis", "given": "Nikolaos", "initials": "N"}, {"family": "Sanjiv", "given": "Kumar", "initials": "K"}, {"family": "Paulin", "given": "Cynthia Bj", "initials": "CB"}, {"family": "Sandhow", "given": "Lakshmi", "initials": "L"}, {"family": "Kutzner", "given": "Juliane", "initials": "J"}, {"family": "Hed Myrberg", "given": "Ida", "initials": "I", "orcid": "0000-0002-8297-2238", "researcher": {"href": "https://publications.scilifelab.se/researcher/276d5d941a3e423cb82b8242eb375cc3.json"}}, {"family": "Bunten", "given": "Sarah S", "initials": "SS"}, {"family": "Axelsson", "given": "Hanna", "initials": "H", "orcid": "0000-0003-2365-1749", "researcher": {"href": "https://publications.scilifelab.se/researcher/63b88c4d11c443f39121c6d93fcff1f0.json"}}, {"family": "Zhang", "given": "Si Min", "initials": "SM"}, {"family": "Rasti", "given": "Azita", "initials": "A"}, {"family": "M\u00e4kel\u00e4", "given": "Petri", "initials": "P"}, {"family": "Coggins", "given": "Si'Ana A", "initials": "SA"}, {"family": "Tao", "given": "Sijia", "initials": "S"}, {"family": "Suman", "given": "Sharda", "initials": "S"}, {"family": "Branca", "given": "Rui M", "initials": "RM"}, {"family": "Mermelekas", "given": "Georgios", "initials": "G"}, {"family": "Wiita", "given": "Elis\u00e9e", "initials": "E"}, {"family": "Lee", "given": "Sun", "initials": "S"}, {"family": "Walfridsson", "given": "Julian", "initials": "J"}, {"family": "Schinazi", "given": "Raymond F", "initials": "RF"}, {"family": "Kim", "given": "Baek", "initials": "B"}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Rassidakis", "given": "Georgios Z", "initials": "GZ"}, {"family": "Pokrovskaja Tamm", "given": "Katja", "initials": "K"}, {"family": "Warpman-Berglund", "given": "Ulrika", "initials": "U"}, {"family": "Heyman", "given": "Mats", "initials": "M"}, {"family": "Grand\u00e9r", "given": "Dan", "initials": "D"}, {"family": "Lehmann", "given": "S\u00f6ren", "initials": "S"}, {"family": "Lundb\u00e4ck", "given": "Thomas", "initials": "T"}, {"family": "Qian", "given": "Hong", "initials": "H"}, {"family": "Henter", "given": "Jan-Inge", "initials": "JI", "orcid": "0000-0002-0629-2126", "researcher": {"href": "https://publications.scilifelab.se/researcher/c1a0d663491c4665a32a612e423dff1b.json"}}, {"family": "Schaller", "given": "Torsten", "initials": "T", "orcid": "0000-0001-9597-4112", "researcher": {"href": "https://publications.scilifelab.se/researcher/c74944db1b4f4fe4a09079f417f8eec6.json"}}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}, {"family": "Herold", "given": "Nikolas", "initials": "N", "orcid": "0000-0001-9468-4543", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a2af6f17f76457680908c36693f2de5.json"}}], "type": "journal article", "published": "2020-03-06", "journal": {"title": "EMBO Mol Med", "issn": "1757-4684", "volume": "12", "issue": "3", "pages": "e10419", "issn-l": "1757-4676"}, "abstract": "The deoxycytidine analogue cytarabine (ara-C) remains the backbone treatment of acute myeloid leukaemia (AML) as well as other haematological and lymphoid malignancies, but must be combined with other chemotherapeutics to achieve cure. Yet, the underlying mechanism dictating synergistic efficacy of combination chemotherapy remains largely unknown. The dNTPase SAMHD1, which regulates dNTP homoeostasis antagonistically to ribonucleotide reductase (RNR), limits ara-C efficacy by hydrolysing the active triphosphate metabolite ara-CTP. Here, we report that clinically used inhibitors of RNR, such as gemcitabine and hydroxyurea, overcome the SAMHD1-mediated barrier to ara-C efficacy in primary blasts and mouse models of AML, displaying SAMHD1-dependent synergy with ara-C. We present evidence that this is mediated by dNTP pool imbalances leading to allosteric reduction of SAMHD1 ara-CTPase activity. Thus, SAMHD1 constitutes a novel biomarker for combination therapies of ara-C and RNR inhibitors with immediate consequences for clinical practice to improve treatment of AML.", "doi": "10.15252/emmm.201910419", "pmid": "31950591", "labels": {"Chemical Biology Consortium Sweden": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC7059017"}], "notes": [], "created": "2020-11-08T14:42:08.378Z", "modified": "2025-10-17T13:04:28.335Z"}, {"entity": "publication", "iuid": "bb89d24bf5de4738810b72a84a0ad0b6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bb89d24bf5de4738810b72a84a0ad0b6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bb89d24bf5de4738810b72a84a0ad0b6"}}, "title": "An atlas of the protein-coding genes in the human, pig, and mouse brain.", "authors": [{"family": "Sj\u00f6stedt", "given": "Evelina", "initials": "E", "orcid": "0000-0002-0327-7377", "researcher": {"href": "https://publications.scilifelab.se/researcher/fdcf6ac54d8343838878c1afbafa32b3.json"}}, {"family": "Zhong", "given": "Wen", "initials": "W", "orcid": "0000-0002-7422-6104", "researcher": {"href": "https://publications.scilifelab.se/researcher/a82c3b7da3b8472392d39ca5f6d5bedb.json"}}, {"family": "Fagerberg", "given": "Linn", "initials": "L", "orcid": "0000-0003-0198-7137", "researcher": {"href": "https://publications.scilifelab.se/researcher/e8db0663a10a4d9e9241457609d5952e.json"}}, {"family": "Karlsson", "given": "Max", "initials": "M", "orcid": "0000-0002-7000-4416", "researcher": {"href": "https://publications.scilifelab.se/researcher/6e1bd9a99e5648c3998c6e0106a07fbc.json"}}, {"family": "Mitsios", "given": "Nicholas", "initials": "N", "orcid": "0000-0001-6243-4953", "researcher": {"href": "https://publications.scilifelab.se/researcher/38efa44f5ed64192b432d6384584f00d.json"}}, {"family": "Adori", "given": "Csaba", "initials": "C"}, {"family": "Oksvold", "given": "Per", "initials": "P", "orcid": "0000-0003-3014-5502", "researcher": {"href": "https://publications.scilifelab.se/researcher/6cdb69ec1f0f428898a2aadceb01062c.json"}}, {"family": "Edfors", "given": "Fredrik", "initials": "F", "orcid": "0000-0002-0017-7987", "researcher": {"href": "https://publications.scilifelab.se/researcher/3f0e8af0b9144bcd9fd566d316008a62.json"}}, {"family": "Limiszewska", "given": "Agnieszka", "initials": "A", "orcid": "0000-0003-1601-8195", "researcher": {"href": "https://publications.scilifelab.se/researcher/a2e7b9e0e376422491d8bd1d76d6f774.json"}}, {"family": "Hikmet", "given": "Feria", "initials": "F", "orcid": "0000-0002-3750-9308", "researcher": {"href": "https://publications.scilifelab.se/researcher/5e8c8f511fef466dafd7d704e17d2e30.json"}}, {"family": "Huang", "given": "Jinrong", "initials": "J", "orcid": "0000-0001-8085-9939", "researcher": {"href": "https://publications.scilifelab.se/researcher/00a7eea9544b457b8b058c98e0f4ee94.json"}}, {"family": "Du", "given": "Yutao", "initials": "Y"}, {"family": "Lin", "given": "Lin", "initials": "L", "orcid": "0000-0002-7546-4948", "researcher": {"href": "https://publications.scilifelab.se/researcher/e6436e2b14cd4a629aeebed48b3ae0a9.json"}}, {"family": "Dong", "given": "Zhanying", "initials": "Z"}, {"family": "Yang", "given": "Ling", "initials": "L", "orcid": "0000-0002-5425-8256", "researcher": {"href": "https://publications.scilifelab.se/researcher/8e150be60a3740b89511174e0fd8fa6e.json"}}, {"family": "Liu", "given": "Xin", "initials": "X", "orcid": "0000-0003-3256-2940", "researcher": {"href": "https://publications.scilifelab.se/researcher/b130e21a82a94eb7acd0333f3e62b6ba.json"}}, {"family": "Jiang", "given": "Hui", "initials": "H"}, {"family": "Xu", "given": "Xun", "initials": "X", "orcid": "0000-0002-5338-5173", "researcher": {"href": "https://publications.scilifelab.se/researcher/c96e82115f8d493ea665e5dfe2a374e9.json"}}, {"family": "Wang", "given": "Jian", "initials": "J"}, {"family": "Yang", "given": "Huanming", "initials": "H", "orcid": "0000-0003-1703-3012", "researcher": {"href": "https://publications.scilifelab.se/researcher/6575b8191e414162b52d26df8d9af26a.json"}}, {"family": "Bolund", "given": "Lars", "initials": "L"}, {"family": "Mardinoglu", "given": "Adil", "initials": "A", "orcid": "0000-0002-4254-6090", "researcher": {"href": "https://publications.scilifelab.se/researcher/da756265658c4ed2a8911644583e07a3.json"}}, {"family": "Zhang", "given": "Cheng", "initials": "C", "orcid": "0000-0002-3721-8586", "researcher": {"href": "https://publications.scilifelab.se/researcher/d1b9559ac41749fa91c4025108947e13.json"}}, {"family": "von Feilitzen", "given": "Kalle", "initials": "K", "orcid": "0000-0002-0257-7554", "researcher": {"href": "https://publications.scilifelab.se/researcher/9f1e309f8d9247458c59e2ecfbd0c079.json"}}, {"family": "Lindskog", "given": "Cecilia", "initials": "C", "orcid": "0000-0001-5611-1015", "researcher": {"href": "https://publications.scilifelab.se/researcher/36b6a0f049274929b64dcb5061ca0588.json"}}, {"family": "Pont\u00e9n", "given": "Fredrik", "initials": "F", "orcid": "0000-0003-0703-3940", "researcher": {"href": "https://publications.scilifelab.se/researcher/a8b56979a6c74891aa277fb28848b6ce.json"}}, {"family": "Luo", "given": "Yonglun", "initials": "Y", "orcid": "0000-0002-0007-7759", "researcher": {"href": "https://publications.scilifelab.se/researcher/0aad9ec706674ed6ab358a445ba1989d.json"}}, {"family": "H\u00f6kfelt", "given": "Tomas", "initials": "T"}, {"family": "Uhl\u00e9n", "given": "Mathias", "initials": "M", "orcid": "0000-0002-4858-8056", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff81da3cb0cf4262873b993a1b06798c.json"}}, {"family": "Mulder", "given": "Jan", "initials": "J", "orcid": "0000-0003-3717-5018", "researcher": {"href": "https://publications.scilifelab.se/researcher/a8443b271929476bb2b569e39bae732c.json"}}], "type": "comparative study", "published": "2020-03-06", "journal": {"title": "Science", "issn": "1095-9203", "volume": "367", "issue": "6482", "pages": "eaay5947", "issn-l": "0036-8075"}, "abstract": "The brain, with its diverse physiology and intricate cellular organization, is the most complex organ of the mammalian body. To expand our basic understanding of the neurobiology of the brain and its diseases, we performed a comprehensive molecular dissection of 10 major brain regions and multiple subregions using a variety of transcriptomics methods and antibody-based mapping. This analysis was carried out in the human, pig, and mouse brain to allow the identification of regional expression profiles, as well as to study similarities and differences in expression levels between the three species. The resulting data have been made available in an open-access Brain Atlas resource, part of the Human Protein Atlas, to allow exploration and comparison of the expression of individual protein-coding genes in various parts of the mammalian brain.", "doi": "10.1126/science.aay5947", "pmid": "32139519", "labels": {"NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "367/6482/eaay5947"}], "notes": [], "created": "2020-12-07T16:26:57.513Z", "modified": "2024-01-16T13:48:42.811Z"}, {"entity": "publication", "iuid": "e7b62282c0ab4fa298b3a15c0daefd80", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e7b62282c0ab4fa298b3a15c0daefd80.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e7b62282c0ab4fa298b3a15c0daefd80"}}, "title": "The Molecular Anatomy of Mouse Skin during Hair Growth and Rest.", "authors": [{"family": "Joost", "given": "Simon", "initials": "S"}, {"family": "Annusver", "given": "Karl", "initials": "K"}, {"family": "Jacob", "given": "Tina", "initials": "T"}, {"family": "Sun", "given": "Xiaoyan", "initials": "X"}, {"family": "Dalessandri", "given": "Tim", "initials": "T"}, {"family": "Sivan", "given": "Unnikrishnan", "initials": "U"}, {"family": "Sequeira", "given": "In\u00eas", "initials": "I"}, {"family": "Sandberg", "given": "Rickard", "initials": "R", "orcid": "0000-0001-6473-1740", "researcher": {"href": "https://publications.scilifelab.se/researcher/048c7c9b9edb4366bac7873daad461cd.json"}}, {"family": "Kasper", "given": "Maria", "initials": "M"}], "type": "journal article", "published": "2020-03-05", "journal": {"volume": "26", "issn": "1875-9777", "issue": "3", "pages": "441-457.e7", "title": "Cell Stem Cell", "issn-l": null}, "abstract": "Skin homeostasis is orchestrated by dozens of cell types that together direct stem cell renewal, lineage commitment, and differentiation. Here, we use single-cell RNA sequencing and single-molecule RNA FISH to provide a systematic molecular atlas of full-thickness skin, determining gene expression profiles and spatial locations that define 56 cell types and states during hair growth and rest. These findings reveal how the outer root sheath (ORS) and inner hair follicle layers coordinate hair production. We found that the ORS is composed of two intermingling but transcriptionally distinct cell types with differing capacities for interactions with stromal cell types. Inner layer cells branch from transcriptionally uncommitted progenitors, and each lineage differentiation passes through an intermediate state. We also provide an online tool to explore this comprehensive skin cell atlas, including epithelial and stromal cells such as fibroblasts, vascular, and immune cells, to spur further discoveries in skin biology.", "doi": "10.1016/j.stem.2020.01.012", "pmid": "32109378", "labels": {"National Genomics Infrastructure": "Service", "Eukaryotic Single Cell Genomics (ESCG)": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S1934-5909(20)30012-6"}], "notes": [], "created": "2020-03-02T10:57:50.903Z", "modified": "2024-01-16T13:48:42.819Z"}, {"entity": "publication", "iuid": "7c491e2498b7430bb6f5ca139240861d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7c491e2498b7430bb6f5ca139240861d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7c491e2498b7430bb6f5ca139240861d"}}, "title": "Stressful Beginnings with Long-Term Consequences.", "authors": [{"family": "Consiglio", "given": "Camila Rosat", "initials": "CR"}, {"family": "Brodin", "given": "Petter", "initials": "P", "orcid": "0000-0002-8103-0046", "researcher": {"href": "https://publications.scilifelab.se/researcher/40097353cdb24e52bf2330eb687042bf.json"}}], "type": "journal article", "published": "2020-03-05", "journal": {"title": "Cell", "issn": "1097-4172", "issn-l": "0092-8674", "volume": "180", "issue": "5", "pages": "820-821"}, "abstract": "Early-life stress can have long-term health consequences, but the mechanisms of this are unknown. In this issue of Cell, Hong et al. demonstrate one such mechanism linking perinatal corticosteroid exposure to reduced CD8+ T cell function later in life and impaired anti-cancer and anti-bacterial immune responses.", "doi": "10.1016/j.cell.2020.02.021", "pmid": "32142672", "labels": {"Cellular Immunomonitoring": "Technology development", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S0092-8674(20)30165-3"}], "notes": [], "created": "2020-04-25T09:24:57.097Z", "modified": "2024-01-16T13:48:42.827Z"}, {"entity": "publication", "iuid": "42a7226b5fea4ab08d62a64a9b5fd25f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/42a7226b5fea4ab08d62a64a9b5fd25f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/42a7226b5fea4ab08d62a64a9b5fd25f"}}, "title": "Short-Range Order and Transport Properties in Mixtures of the Protic Ionic Liquid [C2HIm][TFSI] with Water or Imidazole.", "authors": [{"family": "Hasani", "given": "Mohammad", "initials": "M"}, {"family": "Varela", "given": "Luis Miguel", "initials": "LM", "orcid": "0000-0002-0569-0042", "researcher": {"href": "https://publications.scilifelab.se/researcher/20d34c70032b42e58b69bc37fbda9d2f.json"}}, {"family": "Martinelli", "given": "Anna", "initials": "A", "orcid": "0000-0001-9885-5901", "researcher": {"href": "https://publications.scilifelab.se/researcher/a4adbd00ead04caaaa107e57fbe67c7b.json"}}], "type": "journal article", "published": "2020-03-05", "journal": {"title": "J. Phys. Chem. B", "issn": "1520-5207", "volume": "124", "issue": "9", "pages": "1767-1777", "issn-l": null}, "abstract": "We investigate the effect of adding different molecular cosolvents, water or imidazole, to the protic ionic liquid 1-ethylimidazolium bis(trifluoromethanesulfonyl)imide, i.e., [C2HIm][TFSI]. We explore how the added cosolvent distributes within the ionic liquid by means of molecular dynamics simulations and X-ray scattering. We also analyze the degree of short-range heterogeneity in the resulting mixtures, finding that while imidazole easily mixes with the protic ionic liquid, water tends to form small clusters in its own water-rich domains. These differences are rationalized by invoking the nature of intermolecular interactions. In aqueous mixtures water-water hydrogen bonds are more likely to form than water-ion hydrogen bonds (water-TFSI bonds being particularly weak), while imidazole can interact with both cations and anions. Hence, the cation-anion association is negligibly influenced by the presence of water, whereas the addition of imidazole creates solvent-separated ion pairs and is thus able to also increase the ionicity. As a consequence of these structural and interactional features, transport properties like self-diffusion and ionic conductivity also show different composition dependencies. While the mobility of both ions and solvent is increased considerably by the addition of water, upon adding imidazole this property changes significantly only for molar fractions of imidazole above 0.6. At these molar fractions, which correspond to a base-excess composition, the imidazole/[C2HIm][TFSI] mixture behaves as a glass-forming liquid with suppressed phase transitions, while homomixtures such as imidazole/[HIm][TFSI] can display a eutectic point.", "doi": "10.1021/acs.jpcb.9b10454", "pmid": "31999926", "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [], "notes": [], "created": "2020-12-11T09:12:10.898Z", "modified": "2025-10-17T13:03:57.049Z"}, {"entity": "publication", "iuid": "a5ffc222ff2f4848955dbd9ffdb38a85", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a5ffc222ff2f4848955dbd9ffdb38a85.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a5ffc222ff2f4848955dbd9ffdb38a85"}}, "title": "Genome-wide Association Analysis in Humans Links Nucleotide Metabolism to Leukocyte Telomere Length.", "authors": [{"family": "Li", "given": "Chen", "initials": "C"}, {"family": "Stoma", "given": "Svetlana", "initials": "S"}, {"family": "Lotta", "given": "Luca A", "initials": "LA"}, {"family": "Warner", "given": "Sophie", "initials": "S"}, {"family": "Albrecht", "given": "Eva", "initials": "E"}, {"family": "Allione", "given": "Alessandra", "initials": "A"}, {"family": "Arp", "given": "Pascal P", "initials": "PP"}, {"family": "Broer", "given": "Linda", "initials": "L"}, {"family": "Buxton", "given": "Jessica L", "initials": "JL"}, {"family": "Da Silva Couto Alves", "given": "Alexessander", "initials": "A"}, {"family": "Deelen", "given": "Joris", "initials": "J"}, {"family": "Fedko", "given": "Iryna O", "initials": "IO"}, {"family": "Gordon", "given": "Scott D", "initials": "SD"}, {"family": "Jiang", "given": "Tao", "initials": "T"}, {"family": "Karlsson", "given": "Robert", "initials": "R"}, {"family": "Kerrison", "given": "Nicola", "initials": "N"}, {"family": "Loe", "given": "Taylor K", "initials": "TK"}, {"family": "Mangino", "given": "Massimo", "initials": "M"}, {"family": "Milaneschi", "given": "Yuri", "initials": "Y"}, {"family": "Miraglio", "given": "Benjamin", "initials": "B"}, {"family": "Pervjakova", "given": "Natalia", "initials": "N"}, {"family": "Russo", "given": "Alessia", "initials": "A"}, {"family": "Surakka", "given": "Ida", "initials": "I"}, {"family": "van der Spek", "given": "Ashley", "initials": "A"}, {"family": "Verhoeven", "given": "Josine E", "initials": "JE"}, {"family": "Amin", "given": "Najaf", "initials": "N"}, {"family": "Beekman", "given": "Marian", "initials": "M"}, {"family": "Blakemore", "given": "Alexandra I", "initials": "AI"}, {"family": "Canzian", "given": "Federico", "initials": "F"}, {"family": "Hamby", "given": "Stephen E", "initials": "SE"}, {"family": "Hottenga", "given": "Jouke-Jan", "initials": "JJ"}, {"family": "Jones", "given": "Peter D", "initials": "PD"}, {"family": "Jousilahti", "given": "Pekka", "initials": "P"}, {"family": "M\u00e4gi", "given": "Reedik", "initials": "R"}, {"family": "Medland", "given": "Sarah E", "initials": "SE"}, {"family": "Montgomery", "given": "Grant W", "initials": "GW"}, {"family": "Nyholt", "given": "Dale R", "initials": "DR"}, {"family": "Perola", "given": "Markus", "initials": "M"}, {"family": "Pietil\u00e4inen", "given": "Kirsi H", "initials": "KH"}, {"family": "Salomaa", "given": "Veikko", "initials": "V"}, {"family": "Sillanp\u00e4\u00e4", "given": "Elina", "initials": "E"}, {"family": "Suchiman", "given": "H Eka", "initials": "HE"}, {"family": "van Heemst", "given": "Diana", "initials": "D"}, {"family": "Willemsen", "given": "Gonneke", "initials": "G"}, {"family": "Agudo", "given": "Antonio", "initials": "A"}, {"family": "Boeing", "given": "Heiner", "initials": "H"}, {"family": "Boomsma", "given": "Dorret I", "initials": "DI"}, {"family": "Chirlaque", "given": "Maria-Dolores", "initials": "MD"}, {"family": "Fagherazzi", "given": "Guy", "initials": "G"}, {"family": "Ferrari", "given": "Pietro", "initials": "P"}, {"family": "Franks", "given": "Paul", "initials": "P"}, {"family": "Gieger", "given": "Christian", "initials": "C"}, {"family": "Eriksson", "given": "Johan Gunnar", "initials": "JG"}, {"family": "Gunter", "given": "Marc", "initials": "M"}, {"family": "H\u00e4gg", "given": "Sara", "initials": "S"}, {"family": "Hovatta", "given": "Iiris", "initials": "I"}, {"family": "Imaz", "given": "Liher", "initials": "L"}, {"family": "Kaprio", "given": "Jaakko", "initials": "J"}, {"family": "Kaaks", "given": "Rudolf", "initials": "R"}, {"family": "Key", "given": "Timothy", "initials": "T"}, {"family": "Krogh", "given": "Vittorio", "initials": "V"}, {"family": "Martin", "given": "Nicholas G", "initials": "NG"}, {"family": "Melander", "given": "Olle", "initials": "O"}, {"family": "Metspalu", "given": "Andres", "initials": "A"}, {"family": "Moreno", "given": "Concha", "initials": "C"}, {"family": "Onland-Moret", "given": "N Charlotte", "initials": "NC"}, {"family": "Nilsson", "given": "Peter", "initials": "P", "orcid": "0000-0002-4657-8532", "researcher": {"href": "https://publications.scilifelab.se/researcher/799bcf1cf8cf451296f4535dd4ca9dc0.json"}}, {"family": "Ong", "given": "Ken K", "initials": "KK"}, {"family": "Overvad", "given": "Kim", "initials": "K"}, {"family": "Palli", "given": "Domenico", "initials": "D"}, {"family": "Panico", "given": "Salvatore", "initials": "S"}, {"family": "Pedersen", "given": "Nancy L", "initials": "NL"}, {"family": "Penninx", "given": "Brenda W J H", "initials": "BWJH"}, {"family": "Quir\u00f3s", "given": "J Ram\u00f3n", "initials": "JR"}, {"family": "Jarvelin", "given": "Marjo Riitta", "initials": "MR"}, {"family": "Rodr\u00edguez-Barranco", "given": "Miguel", "initials": "M"}, {"family": "Scott", "given": "Robert A", "initials": "RA"}, {"family": "Severi", "given": "Gianluca", "initials": "G"}, {"family": "Slagboom", "given": "P Eline", "initials": "PE"}, {"family": "Spector", "given": "Tim D", "initials": "TD"}, {"family": "Tjonneland", "given": "Anne", "initials": "A"}, {"family": "Trichopoulou", "given": "Antonia", "initials": "A"}, {"family": "Tumino", "given": "Rosario", "initials": "R"}, {"family": "Uitterlinden", "given": "Andr\u00e9 G", "initials": "AG"}, {"family": "van der Schouw", "given": "Yvonne T", "initials": "YT"}, {"family": "van Duijn", "given": "Cornelia M", "initials": "CM"}, {"family": "Weiderpass", "given": "Elisabete", "initials": "E"}, {"family": "Denchi", "given": "Eros Lazzerini", "initials": "EL"}, {"family": "Matullo", "given": "Giuseppe", "initials": "G"}, {"family": "Butterworth", "given": "Adam S", "initials": "AS"}, {"family": "Danesh", "given": "John", "initials": "J"}, {"family": "Samani", "given": "Nilesh J", "initials": "NJ"}, {"family": "Wareham", "given": "Nicholas J", "initials": "NJ"}, {"family": "Nelson", "given": "Christopher P", "initials": "CP"}, {"family": "Langenberg", "given": "Claudia", "initials": "C"}, {"family": "Codd", "given": "Veryan", "initials": "V"}], "type": "journal article", "published": "2020-03-05", "journal": {"title": "Am. J. Hum. Genet.", "issn": "1537-6605", "volume": "106", "issue": "3", "pages": "389-404", "issn-l": "0002-9297"}, "abstract": "Leukocyte telomere length (LTL) is a heritable biomarker of genomic aging. In this study, we perform a genome-wide meta-analysis of LTL by pooling densely genotyped and imputed association results across large-scale European-descent studies including up to 78,592 individuals. We identify 49 genomic regions at a false dicovery rate (FDR) < 0.05 threshold and prioritize genes at 31, with five highlighting nucleotide metabolism as an important regulator of LTL. We report six genome-wide significant loci in or near SENP7, MOB1B, CARMIL1, PRRC2A, TERF2, and RFWD3, and our results support recently identified PARP1, POT1, ATM, and MPHOSPH6 loci. Phenome-wide analyses in >350,000 UK Biobank participants suggest that genetically shorter telomere length increases the risk of hypothyroidism and decreases the risk of thyroid cancer, lymphoma, and a range of proliferative conditions. Our results replicate previously reported associations with increased risk of coronary artery disease and lower risk for multiple cancer types. Our findings substantially expand current knowledge on genes that regulate LTL and their impact on human health and disease.", "doi": "10.1016/j.ajhg.2020.02.006", "pmid": "32109421", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "S0002-9297(20)30048-3"}, {"db": "pmc", "key": "PMC7058826"}], "notes": [], "created": "2020-03-03T12:57:27.050Z", "modified": "2021-11-10T12:53:17.953Z"}, {"entity": "publication", "iuid": "02683ab21f254d36849d8855f6b21614", "links": {"self": {"href": "https://publications.scilifelab.se/publication/02683ab21f254d36849d8855f6b21614.json"}, "display": {"href": "https://publications.scilifelab.se/publication/02683ab21f254d36849d8855f6b21614"}}, "title": "Epiphyseal Cartilage Formation Involves Differential Dynamics of Various Cellular Populations During Embryogenesis.", "authors": [{"family": "Zhang", "given": "Yi", "initials": "Y"}, {"family": "Annusver", "given": "Karl", "initials": "K"}, {"family": "Sunadome", "given": "Kazunori", "initials": "K"}, {"family": "Kameneva", "given": "Polina", "initials": "P"}, {"family": "Edwards", "given": "Steven", "initials": "S"}, {"family": "Lei", "given": "Guanghua", "initials": "G"}, {"family": "Kasper", "given": "Maria", "initials": "M"}, {"family": "Chagin", "given": "Andrei S", "initials": "AS"}, {"family": "Adameyko", "given": "Igor", "initials": "I"}, {"family": "Xie", "given": "Meng", "initials": "M"}], "type": "journal article", "published": "2020-03-05", "journal": {"title": "Front Cell Dev Biol", "issn": "2296-634X", "volume": "8", "pages": "122", "issn-l": null}, "abstract": "A joint connects two or more bones together to form a functional unit that allows different types of bending and movement. Little is known about how the opposing ends of the connected bones are developed. Here, applying various lineage tracing strategies we demonstrate that progenies of Gdf5-, Col2-, Prrx1-, and Gli1-positive cells contribute to the growing epiphyseal cartilage in a spatially asymmetrical manner. In addition, we reveal that cells in the cartilaginous anlagen are likely to be the major sources for epiphyseal cartilage. Moreover, Gli1-positive cells are found to proliferate along the skeletal edges toward the periarticular region of epiphyseal surface. Finally, a switch in the mechanism of growth from cell division to cell influx likely occurs in the epiphyseal cartilage when joint cavitation has completed. Altogether, our findings reveal an asymmetrical mechanism of growth that drives the formation of epiphyseal cartilage ends, which might implicate on how the articular surface of these skeletal elements acquires their unique and sophisticated shape during embryonic development.", "doi": "10.3389/fcell.2020.00122", "pmid": "32211405", "labels": {"Integrated Microscopy Technologies Stockholm": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7066500"}], "notes": [], "created": "2023-06-07T12:06:39.430Z", "modified": "2023-06-07T12:06:39.434Z"}, {"entity": "publication", "iuid": "969d734e66764ff9b82ae2cfe1712a9a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/969d734e66764ff9b82ae2cfe1712a9a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/969d734e66764ff9b82ae2cfe1712a9a"}}, "title": "One-Pot Production of RNA in High Yield and Purity Through Cleaving Tandem Transcripts.", "authors": [{"family": "Feyrer", "given": "Hannes", "initials": "H"}, {"family": "Munteanu", "given": "Raluca", "initials": "R"}, {"family": "Baronti", "given": "Lorenzo", "initials": "L"}, {"family": "Petzold", "given": "Katja", "initials": "K", "orcid": "0000-0001-9470-0347", "researcher": {"href": "https://publications.scilifelab.se/researcher/946f0162cdb0411493968f363c943ad5.json"}}], "type": "journal article", "published": "2020-03-04", "journal": {"title": "Molecules", "issn": "1420-3049", "volume": "25", "issue": "5", "issn-l": "1420-3049"}, "abstract": "There is an increasing demand for efficient and robust production of short RNA molecules in both pharmaceutics and research. A standard method is in vitro transcription by T7 RNA polymerase. This method is sequence-dependent on efficiency and is limited to products longer than ~12 nucleotides. Additionally, the native initiation sequence is required to achieve high yields, putting a strain on sequence variability. Deviations from this sequence can lead to side products, requiring laborious purification, further decreasing yield. We here present transcribing tandem repeats of the target RNA sequence followed by site-specific cleavage to obtain RNA in high purity and yield. This approach makes use of a plasmid DNA template and RNase H-directed cleavage of the transcript. The method is simpler and faster than previous protocols, as it can be performed as one pot synthesis and provides at the same time higher yields of RNA.", "doi": "10.3390/molecules25051142", "pmid": "32143353", "labels": {"Protein Science Facility (PSF)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7179201"}, {"db": "pii", "key": "molecules25051142"}], "notes": [], "created": "2024-04-03T14:24:36.719Z", "modified": "2024-04-03T14:24:36.773Z"}, {"entity": "publication", "iuid": "67b440a208864ecea283f09dd7ca7f80", "links": {"self": {"href": "https://publications.scilifelab.se/publication/67b440a208864ecea283f09dd7ca7f80.json"}, "display": {"href": "https://publications.scilifelab.se/publication/67b440a208864ecea283f09dd7ca7f80"}}, "title": "Transcriptomic resources for evolutionary studies in flat periwinkles and related species.", "authors": [{"family": "Marques", "given": "Jo\u00e3o P", "initials": "JP", "orcid": "0000-0001-9834-1361", "researcher": {"href": "https://publications.scilifelab.se/researcher/7bb0a67732e44e108fe1f58f86ce4ef2.json"}}, {"family": "Sotelo", "given": "Graciela", "initials": "G"}, {"family": "Galindo", "given": "Juan", "initials": "J"}, {"family": "Chaube", "given": "Pragya", "initials": "P"}, {"family": "Costa", "given": "Diana", "initials": "D"}, {"family": "Afonso", "given": "Sandra", "initials": "S"}, {"family": "Panova", "given": "Marina", "initials": "M"}, {"family": "Nowick", "given": "Katja", "initials": "K"}, {"family": "Butlin", "given": "Roger", "initials": "R", "orcid": "0000-0003-4736-0954", "researcher": {"href": "https://publications.scilifelab.se/researcher/e510a963ebeb4e8c8af68b10a001a326.json"}}, {"family": "Hollander", "given": "Johan", "initials": "J"}, {"family": "Faria", "given": "Rui", "initials": "R"}], "type": "dataset", "published": "2020-03-03", "journal": {"title": "Sci Data", "issn": "2052-4463", "volume": "7", "issue": "1", "pages": "73", "issn-l": "2052-4463"}, "abstract": "The flat periwinkles, Littorina fabalis and L. obtusata, comprise two sister gastropod species that have an enormous potential to elucidate the mechanisms involved in ecological speciation in the marine realm. However, the molecular resources currently available for these species are still scarce. In order to circumvent this limitation, we used RNA-seq data to characterize the transcriptome of four individuals from each species sampled in different locations across the Iberian Peninsula. Four de novo transcriptome assemblies were generated, as well as a pseudo-reference using the L. saxatilis reference transcriptome as backbone. After transcripts' annotation, variant calling resulted in the identification of 19,072 to 45,340 putatively species-diagnostic SNPs. The discriminatory power of a subset of these SNPs was validated by implementing an independent genotyping assay to characterize reference populations, resulting in an accurate classification of individuals into each species and in the identification of hybrids between the two. These data comprise valuable genomic resources for a wide range of evolutionary and conservation studies in flat periwinkles and related taxa.", "doi": "10.1038/s41597-020-0408-8", "pmid": "32127542", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41597-020-0408-8"}, {"db": "pmc", "key": "PMC7054417"}], "notes": [], "created": "2020-03-16T09:47:51.783Z", "modified": "2021-11-10T12:53:19.043Z"}, {"entity": "publication", "iuid": "fc7a25ffb3114b019ba788d35be80ecc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/fc7a25ffb3114b019ba788d35be80ecc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/fc7a25ffb3114b019ba788d35be80ecc"}}, "title": "Oral Microbiota Profile Associates with Sugar Intake and Taste Preference Genes.", "authors": [{"family": "Esberg", "given": "Anders", "initials": "A", "orcid": "0000-0002-4430-8125", "researcher": {"href": "https://publications.scilifelab.se/researcher/a6610f154ad749a49a8f5d89382c6b1b.json"}}, {"family": "Haworth", "given": "Simon", "initials": "S", "orcid": "0000-0001-7793-7326", "researcher": {"href": "https://publications.scilifelab.se/researcher/43fa9fb331c849b58d4ac4b14f04fbda.json"}}, {"family": "Hassl\u00f6f", "given": "Pamela", "initials": "P"}, {"family": "Lif Holgerson", "given": "Pernilla", "initials": "P", "orcid": "0000-0002-2779-5865", "researcher": {"href": "https://publications.scilifelab.se/researcher/90cb42e842044260888df6e0a10afdd1.json"}}, {"family": "Johansson", "given": "Ingegerd", "initials": "I", "orcid": "0000-0002-9227-8434", "researcher": {"href": "https://publications.scilifelab.se/researcher/ee3e20587b664a42a880870f1648160a.json"}}], "type": "clinical trial", "published": "2020-03-03", "journal": {"title": "Nutrients", "issn": "2072-6643", "volume": "12", "issue": "3", "pages": "681", "issn-l": "2072-6643"}, "abstract": "Oral microbiota ecology is influenced by environmental and host conditions, but few studies have evaluated associations between untargeted measures of the entire oral microbiome and potentially relevant environmental and host factors. This study aimed to identify salivary microbiota cluster groups using hierarchical cluster analyses (Wards method) based on 16S rRNA gene amplicon sequencing, and identify lifestyle and host factors which were associated with these groups. Group members (n = 175) were distinctly separated by microbiota profiles and differed in reported sucrose intake and allelic variation in the taste-preference-associated genes TAS1R1 (rs731024) and GNAT3 (rs2074673). Groups with higher sucrose intake were either characterized by a wide panel of species or phylotypes with fewer aciduric species, or by a narrower profile that included documented aciduric- and caries-associated species. The inferred functional profiles of the latter type were dominated by metabolic pathways associated with the carbohydrate metabolism with enrichment of glycosidase functions. In conclusion, this study supported in vivo associations between sugar intake and oral microbiota ecology, but it also found evidence for a variable microbiota response to sugar, highlighting the importance of modifying host factors and microbes beyond the commonly targeted acidogenic and acid-tolerant species. The results should be confirmed under controlled settings with comprehensive phenotypic and genotypic data.", "doi": "10.3390/nu12030681", "pmid": "32138214", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "nu12030681"}, {"db": "pmc", "key": "PMC7146170"}], "notes": [], "created": "2020-03-16T09:47:51.000Z", "modified": "2021-11-10T12:53:20.230Z"}, {"entity": "publication", "iuid": "a223b2180f754d79971096d57b714ee6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a223b2180f754d79971096d57b714ee6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a223b2180f754d79971096d57b714ee6"}}, "title": "Single-cell analysis of human ovarian cortex identifies distinct cell populations but no oogonial stem cells.", "authors": [{"family": "Wagner", "given": "Magdalena", "initials": "M", "orcid": "0000-0002-6266-1248", "researcher": {"href": "https://publications.scilifelab.se/researcher/124ac27397f845a68732369680da7c5a.json"}}, {"family": "Yoshihara", "given": "Masahito", "initials": "M", "orcid": "0000-0002-8915-9282", "researcher": {"href": "https://publications.scilifelab.se/researcher/4303ab7a18254bb59f8e2386a7f7fb0a.json"}}, {"family": "Douagi", "given": "Iyadh", "initials": "I", "orcid": "0000-0002-3221-8667", "researcher": {"href": "https://publications.scilifelab.se/researcher/5a19504ddb2544bca5aeab9abf885b13.json"}}, {"family": "Damdimopoulos", "given": "Anastasios", "initials": "A"}, {"family": "Panula", "given": "Sarita", "initials": "S"}, {"family": "Petropoulos", "given": "Sophie", "initials": "S"}, {"family": "Lu", "given": "Haojiang", "initials": "H"}, {"family": "Pettersson", "given": "Karin", "initials": "K"}, {"family": "Palm", "given": "Kerstin", "initials": "K"}, {"family": "Katayama", "given": "Shintaro", "initials": "S"}, {"family": "Hovatta", "given": "Outi", "initials": "O", "orcid": "0000-0001-5395-3807", "researcher": {"href": "https://publications.scilifelab.se/researcher/f822ca12dfe0462b99c06e57cace4ce0.json"}}, {"family": "Kere", "given": "Juha", "initials": "J", "orcid": "0000-0003-1974-0271", "researcher": {"href": "https://publications.scilifelab.se/researcher/102085fb1c3147ceaf8dcb7651df1303.json"}}, {"family": "Lanner", "given": "Fredrik", "initials": "F", "orcid": "0000-0002-2771-7445", "researcher": {"href": "https://publications.scilifelab.se/researcher/ba53ce48a35d413eb86cd104488ce669.json"}}, {"family": "Damdimopoulou", "given": "Pauliina", "initials": "P", "orcid": "0000-0001-8458-0855", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d258c0f0d9b417ea4608769fc3ebaaf.json"}}], "type": "journal article", "published": "2020-03-02", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "11", "issue": "1", "pages": "1147", "issn-l": "2041-1723"}, "abstract": "The human ovary orchestrates sex hormone production and undergoes monthly structural changes to release mature oocytes. The outer lining of the ovary (cortex) has a key role in defining fertility in women as it harbors the ovarian reserve. It has been postulated that putative oogonial stem cells exist in the ovarian cortex and that these can be captured by DDX4 antibody isolation. Here, we report single-cell transcriptomes and cell surface antigen profiles of over 24,000 cells from high quality ovarian cortex samples from 21 patients. Our data identify transcriptional profiles of six main cell types; oocytes, granulosa cells, immune cells, endothelial cells, perivascular cells, and stromal cells. Cells captured by DDX4 antibody are perivascular cells, not oogonial stem cells. Our data do not support the existence of germline stem cells in adult human ovaries, thereby reinforcing the dogma of a limited ovarian reserve.", "doi": "10.1038/s41467-020-14936-3", "pmid": "32123174", "labels": {"Eukaryotic Single Cell Genomics (ESCG)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-14936-3"}, {"db": "pmc", "key": "PMC7052271"}], "notes": [], "created": "2020-03-03T10:20:08.878Z", "modified": "2024-01-16T13:48:42.834Z"}, {"entity": "publication", "iuid": "94cee12374ed48199a86e42298ad1b40", "links": {"self": {"href": "https://publications.scilifelab.se/publication/94cee12374ed48199a86e42298ad1b40.json"}, "display": {"href": "https://publications.scilifelab.se/publication/94cee12374ed48199a86e42298ad1b40"}}, "title": "Metabolomics analyses in non-diabetic middle-aged individuals reveal metabolites impacting early glucose disturbances and insulin sensitivity.", "authors": [{"family": "Bos", "given": "Maxime M", "initials": "MM", "orcid": "0000-0001-5028-4820", "researcher": {"href": "https://publications.scilifelab.se/researcher/c153ddd8f237477bbb07287046880f6c.json"}}, {"family": "Noordam", "given": "Raymond", "initials": "R"}, {"family": "Bennett", "given": "Kate", "initials": "K"}, {"family": "Beekman", "given": "Marian", "initials": "M"}, {"family": "Mook-Kanamori", "given": "Dennis O", "initials": "DO"}, {"family": "Willems van Dijk", "given": "Ko", "initials": "K"}, {"family": "Slagboom", "given": "P Eline", "initials": "PE"}, {"family": "Lundstedt", "given": "Torbj\u00f6rn", "initials": "T"}, {"family": "Surowiec", "given": "Izabella", "initials": "I"}, {"family": "van Heemst", "given": "Diana", "initials": "D"}], "type": "journal article", "published": "2020-03-02", "journal": {"title": "Metabolomics", "issn": "1573-3890", "volume": "16", "issue": "3", "pages": "35", "issn-l": "1573-3882"}, "abstract": "Several plasma metabolites have been associated with insulin resistance and type 2 diabetes mellitus.\n\nWe aimed to identify plasma metabolites associated with different indices of early disturbances in glucose metabolism and insulin sensitivity.\n\nThis cross-sectional study was conducted in a subsample of the Leiden Longevity Study comprising individuals without a history of diabetes mellitus (n = 233) with a mean age of 63.3 \u00b1 6.7 years of which 48.1% were men. We tested for associations of fasting glucose, fasting insulin, HOMA-IR, Matsuda Index, Insulinogenic Index and glycated hemoglobin with metabolites (Swedish Metabolomics Platform) using linear regression analysis adjusted for age, sex and BMI. Results were validated internally using an independent metabolomics platform (Biocrates platform) and replicated externally in the independent Netherlands Epidemiology of Obesity (NEO) study (Metabolon platform) (n = 545, mean age of 55.8 \u00b1 6.0 years of which 48.6% were men). Moreover, in the NEO study, we replicated our analyses in individuals with diabetes mellitus (cases: n = 36; controls = 561).\n\nOut of the 34 metabolites, a total of 12 plasma metabolites were associated with different indices of disturbances in glucose metabolism and insulin sensitivity in individuals without diabetes mellitus. These findings were validated using a different metabolomics platform as well as in an independent cohort of non-diabetics. Moreover, tyrosine, alanine, valine, tryptophan and alpha-ketoglutaric acid levels were higher in individuals with diabetes mellitus.\n\nWe found several plasma metabolites that are associated with early disturbances in glucose metabolism and insulin sensitivity of which five were also higher in individuals with diabetes mellitus.", "doi": "10.1007/s11306-020-01653-7", "pmid": "32124065", "labels": {"Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pii", "key": "10.1007/s11306-020-01653-7"}, {"db": "pmc", "key": "PMC7051926"}], "notes": [], "created": "2020-12-11T11:56:08.922Z", "modified": "2025-10-17T13:03:16.894Z"}, {"entity": "publication", "iuid": "8b53a25058b940edaec9d79de8be4fff", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8b53a25058b940edaec9d79de8be4fff.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8b53a25058b940edaec9d79de8be4fff"}}, "title": "Tumor localized agonistic anti-CD40 therapy and beyond.", "authors": [{"family": "Eltahir", "given": "Mohamed", "initials": "M"}, {"family": "Persson", "given": "Helena", "initials": "H"}, {"family": "Mangsbo", "given": "Sara", "initials": "S"}], "type": "editorial", "published": "2020-03-00", "journal": {"title": "Expert Opin Biol Ther", "issn": "1744-7682", "issn-l": null, "volume": "20", "issue": "3", "pages": "215-217"}, "abstract": null, "doi": "10.1080/14712598.2020.1713084", "pmid": "31920122", "labels": {"Drug Discovery and Development": "Collaborative"}, "xrefs": [], "notes": [], "created": "2020-12-02T15:21:42.786Z", "modified": "2025-10-17T13:05:08.069Z"}, {"entity": "publication", "iuid": "202e5326e1f74688bebee61065aa45e6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/202e5326e1f74688bebee61065aa45e6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/202e5326e1f74688bebee61065aa45e6"}}, "title": "The nf-core framework for community-curated bioinformatics pipelines.", "authors": [{"family": "Ewels", "given": "Philip A", "initials": "PA", "orcid": "0000-0003-4101-2502", "researcher": {"href": "https://publications.scilifelab.se/researcher/9d0fd82fe18b41539a761c55075f31d6.json"}}, {"family": "Peltzer", "given": "Alexander", "initials": "A", "orcid": "0000-0002-6503-2180", "researcher": {"href": "https://publications.scilifelab.se/researcher/2bc79fd3ce6b40d989966e0dbe88487c.json"}}, {"family": "Fillinger", "given": "Sven", "initials": "S", "orcid": "0000-0001-8835-2219", "researcher": {"href": "https://publications.scilifelab.se/researcher/3e2007321e9641c2bcc17ead2e037a5b.json"}}, {"family": "Patel", "given": "Harshil", "initials": "H", "orcid": "0000-0003-2707-7940", "researcher": {"href": "https://publications.scilifelab.se/researcher/fcb1a5f414814b5096deac0f1a61cbaa.json"}}, {"family": "Alneberg", "given": "Johannes", "initials": "J"}, {"family": "Wilm", "given": "Andreas", "initials": "A"}, {"family": "Garcia", "given": "Maxime Ulysse", "initials": "MU", "orcid": "0000-0003-2827-9261", "researcher": {"href": "https://publications.scilifelab.se/researcher/8cf9b1b223f04296adcb6bd091c548de.json"}}, {"family": "Di Tommaso", "given": "Paolo", "initials": "P"}, {"family": "Nahnsen", "given": "Sven", "initials": "S", "orcid": "0000-0002-4375-0691", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b0b5e235dcc49bcb07248a1053cb610.json"}}], "type": "letter", "published": "2020-03-00", "journal": {"volume": "38", "issn": "1546-1696", "issue": "3", "pages": "276-278", "title": "Nat. Biotechnol.", "issn-l": "1087-0156"}, "abstract": "The standardization, portability and reproducibility of analysis pipelines are key issues within the bioinformatics community. Most bioinformatics pipelines are designed for use on-premises; as a result, the associated software dependencies and execution logic are likely to be tightly coupled with proprietary computing environments. This can make it difficult or even impossible for others to reproduce the ensuing results, which is a fundamental requirement for the validation of scientific findings. Here, we introduce the nf-core framework as a means for the development of collaborative, peer-reviewed, best-practice analysis pipelines (Fig. 1). All nf-core pipelines are written in Nextflow and so inherit the ability to be executed on most computational infrastructures, as well as having native support for container technologies such as Docker and Singularity. The nf-core community (Supplementary Fig. 1) has developed a suite of tools that automate pipeline creation, testing, deployment and synchronization. Our goal is to provide a framework for high-quality bioinformatics pipelines that can be used across all institutions and research facilities.", "doi": "10.1038/s41587-020-0439-x", "pmid": "32055031", "labels": {"National Genomics Infrastructure": "Technology development", "NGI Stockholm (Genomics Applications)": "Technology development", "NGI Stockholm (Genomics Production)": "Technology development"}, "xrefs": [{"db": "pii", "key": "10.1038/s41587-020-0439-x"}], "notes": [], "created": "2020-06-01T16:52:53.192Z", "modified": "2021-11-10T12:53:28.620Z"}, {"entity": "publication", "iuid": "1dc0cba1f4bc4a469774e55e3d8fe100", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1dc0cba1f4bc4a469774e55e3d8fe100.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1dc0cba1f4bc4a469774e55e3d8fe100"}}, "title": "Synthesis, Evaluation and Proposed Binding Pose of Substituted Spiro-Oxindole Dihydroquinazolinones as IRAP Inhibitors.", "authors": [{"family": "Engen", "given": "Karin", "initials": "K"}, {"family": "Vanga", "given": "Sudarsana Reddy", "initials": "SR"}, {"family": "Lundb\u00e4ck", "given": "Thomas", "initials": "T", "orcid": "0000-0002-8145-7808", "researcher": {"href": "https://publications.scilifelab.se/researcher/e13df787cb884549bcf333aba4e6f010.json"}}, {"family": "Agalo", "given": "Faith", "initials": "F"}, {"family": "Konda", "given": "Vivek", "initials": "V"}, {"family": "Jensen", "given": "Annika Jenmalm", "initials": "AJ"}, {"family": "\u00c5qvist", "given": "Johan", "initials": "J", "orcid": "0000-0003-2091-0610", "researcher": {"href": "https://publications.scilifelab.se/researcher/9777a1c6e1bd4181bc46dce4be3c2146.json"}}, {"family": "Guti\u00e9rrez-de-Ter\u00e1n", "given": "Hugo", "initials": "H"}, {"family": "Hallberg", "given": "Mathias", "initials": "M"}, {"family": "Larhed", "given": "Mats", "initials": "M", "orcid": "0000-0001-6258-0635", "researcher": {"href": "https://publications.scilifelab.se/researcher/011ee4a03a534099a5d71b0fdd6dbe81.json"}}, {"family": "Rosenstr\u00f6m", "given": "Ulrika", "initials": "U", "orcid": "0000-0002-0817-8140", "researcher": {"href": "https://publications.scilifelab.se/researcher/6cd5910fdd8c4f1b87d18223b11e3821.json"}}], "type": "journal article", "published": "2020-03-00", "journal": {"volume": "9", "issn": "2191-1363", "issue": "3", "pages": "325-337", "title": "ChemistryOpen", "issn-l": "2191-1363"}, "abstract": "Insulin-regulated aminopeptidase (IRAP) is a new potential macromolecular target for drugs aimed for treatment of cognitive disorders. Inhibition of IRAP by angiotensin IV (Ang IV) improves the memory and learning in rats. The majority of the known IRAP inhibitors are peptidic in character and suffer from poor pharmacokinetic properties. Herein, we present a series of small non-peptide IRAP inhibitors derived from a spiro-oxindole dihydroquinazolinone screening hit (pIC50 5.8). The compounds were synthesized either by a simple microwave (MW)-promoted three-component reaction, or by a two-step one-pot procedure. For decoration of the oxindole ring system, rapid MW-assisted Suzuki-Miyaura cross-couplings (1 min) were performed. A small improvement of potency (pIC50 6.6 for the most potent compound) and an increased solubility could be achieved. As deduced from computational modelling and MD simulations it is proposed that the S-configuration of the spiro-oxindole dihydroquinazolinones accounts for the inhibition of IRAP.", "doi": "10.1002/open.201900344", "pmid": "32154052", "labels": {"Chemical Biology Consortium Sweden": "Collaborative"}, "xrefs": [{"db": "pii", "key": "OPEN201900344"}, {"db": "pmc", "key": "PMC7050655"}], "notes": [], "created": "2020-03-04T13:11:28.870Z", "modified": "2025-10-17T13:04:28.346Z"}, {"entity": "publication", "iuid": "cc640c9f07fa4f81aa6ecd3aa9fdf7df", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cc640c9f07fa4f81aa6ecd3aa9fdf7df.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cc640c9f07fa4f81aa6ecd3aa9fdf7df"}}, "title": "Structure of a minimal photosystem I from the green alga Dunaliella salina.", "authors": [{"family": "Perez-Boerema", "given": "Annemarie", "initials": "A", "orcid": "0000-0002-1180-5838", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a711071c6844bdcb4c151971774435f.json"}}, {"family": "Klaiman", "given": "Daniel", "initials": "D", "orcid": "0000-0002-3807-6591", "researcher": {"href": "https://publications.scilifelab.se/researcher/37d495f21e6f4d9f8ef482f80ba11442.json"}}, {"family": "Caspy", "given": "Ido", "initials": "I", "orcid": "0000-0003-1981-1017", "researcher": {"href": "https://publications.scilifelab.se/researcher/a61b089ee32c4d9088ce16e1603ebcce.json"}}, {"family": "Netzer-El", "given": "Sigal Y", "initials": "SY"}, {"family": "Amunts", "given": "Alexey", "initials": "A", "orcid": "0000-0002-5302-1740", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7d0bf36ad1a47f5b5b88f78d1e15395.json"}}, {"family": "Nelson", "given": "Nathan", "initials": "N", "orcid": "0000-0003-3588-7265", "researcher": {"href": "https://publications.scilifelab.se/researcher/fbfaea6e08764d5ba01172f6f2b01030.json"}}], "type": "journal article", "published": "2020-03-00", "journal": {"volume": "6", "issn": "2055-0278", "issue": "3", "pages": "321-327", "title": "NPLANTS", "issn-l": "2055-0278"}, "abstract": "Solar energy harnessed by oxygenic photosynthesis supports most of the life forms on Earth. In eukaryotes, photosynthesis occurs in chloroplasts and is achieved by membrane-embedded macromolecular complexes that contain core and peripheral antennae with multiple pigments. The structure of photosystem I (PSI) comprises the core and light-harvesting (LHCI) complexes, which together form PSI-LHCI. Here we determined the structure of PSI-LHCI from the salt-tolerant green alga Dunaliella salina using X-ray crystallography and electron cryo-microscopy. Our results reveal a previously undescribed configuration of the PSI core. It is composed of only 7 subunits, compared with 14-16 subunits in plants and the alga Chlamydomonas reinhardtii, and forms the smallest known PSI. The LHCI is poorly conserved at the sequence level and binds to pigments that form new energy pathways, and the interactions between the individual Lhca1-4 proteins are weakened. Overall, the data indicate the PSI of D. salina represents a different type of the molecular organization that provides important information for reconstructing the plasticity and evolution of PSI.", "doi": "10.1038/s41477-020-0611-9", "pmid": "32123351", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41477-020-0611-9"}], "notes": [], "created": "2020-03-10T11:57:34.902Z", "modified": "2021-11-10T12:53:30.915Z"}, {"entity": "publication", "iuid": "ab5a9cefcf044daba4246362a58f1356", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ab5a9cefcf044daba4246362a58f1356.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ab5a9cefcf044daba4246362a58f1356"}}, "title": "PIRIN2 suppresses S-type lignin accumulation in a noncell-autonomous manner in Arabidopsis xylem elements.", "authors": [{"family": "Zhang", "given": "Bo", "initials": "B"}, {"family": "Sztojka", "given": "Bernadette", "initials": "B"}, {"family": "Escamez", "given": "Sacha", "initials": "S"}, {"family": "Vanholme", "given": "Ruben", "initials": "R"}, {"family": "Hedenstr\u00f6m", "given": "Mattias", "initials": "M"}, {"family": "Wang", "given": "Yin", "initials": "Y"}, {"family": "Turumtay", "given": "Halbay", "initials": "H"}, {"family": "Gorzs\u00e1s", "given": "Andr\u00e1s", "initials": "A", "orcid": "0000-0002-2298-8844", "researcher": {"href": "https://publications.scilifelab.se/researcher/8070792ccead4c809c89943d84cf0e03.json"}}, {"family": "Boerjan", "given": "Wout", "initials": "W", "orcid": "0000-0003-1495-510X", "researcher": {"href": "https://publications.scilifelab.se/researcher/c8215f848a3047669e8896145e8db4b5.json"}}, {"family": "Tuominen", "given": "Hannele", "initials": "H", "orcid": "0000-0002-4949-3702", "researcher": {"href": "https://publications.scilifelab.se/researcher/0fe575e1cb054ab08b57e05d3a1ee28d.json"}}], "type": "journal article", "published": "2020-03-00", "journal": {"title": "New Phytol.", "issn": "1469-8137", "volume": "225", "issue": "5", "pages": "1923-1935", "issn-l": "0028-646X"}, "abstract": "PIRIN (PRN) genes encode cupin domain-containing proteins that function as transcriptional co-regulators in humans but that are poorly described in plants. A previous study in xylogenic cell cultures of Zinnia elegans suggested a role for a PRN protein in lignification. This study aimed to identify the function of Arabidopsis (Arabidopsis thaliana) PRN proteins in lignification of xylem tissues. Chemical composition of the secondary cell walls was analysed in Arabidopsis stems and/or hypocotyls by pyrolysis-gas chromatography/mass spectrometry, 2D-nuclear magnetic resonance and phenolic profiling. Secondary cell walls of individual xylem elements were chemotyped by Fourier transform infrared and Raman microspectroscopy. Arabidopsis PRN2 suppressed accumulation of S-type lignin in Arabidopsis stems and hypocotyls. PRN2 promoter activity and PRN2:GFP fusion protein were localised specifically in cells next to the vessel elements, suggesting a role for PRN2 in noncell-autonomous lignification of xylem vessels. Accordingly, PRN2 modulated lignin chemistry in the secondary cell walls of the neighbouring vessel elements. These results indicate that PRN2 suppresses S-type lignin accumulation in the neighbourhood of xylem vessels to bestow G-type enriched lignin composition on the secondary cell walls of the vessel elements. Gene expression analyses suggested that PRN2 function is mediated by regulation of the expression of the lignin-biosynthetic genes.", "doi": "10.1111/nph.16271", "pmid": "31625609", "labels": {"Swedish NMR Centre": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC7027918"}, {"db": "GENBANK", "key": "At3g59220"}, {"db": "GENBANK", "key": "At2g43120"}, {"db": "GENBANK", "key": "At3g59260"}, {"db": "GENBANK", "key": "At1g50590"}, {"db": "GENBANK", "key": "At2g37040"}, {"db": "GENBANK", "key": "At2g30490"}, {"db": "GENBANK", "key": "At1g51680"}, {"db": "GENBANK", "key": "At2g40890"}, {"db": "GENBANK", "key": "At5g48930"}, {"db": "GENBANK", "key": "At4g34050"}, {"db": "GENBANK", "key": "At1g15950"}, {"db": "GENBANK", "key": "At4g36220"}, {"db": "GENBANK", "key": "At5g54160"}, {"db": "GENBANK", "key": "At4g34230"}, {"db": "GENBANK", "key": "At5g62380"}, {"db": "GENBANK", "key": "At1g71930"}, {"db": "GENBANK", "key": "At2g46770"}, {"db": "GENBANK", "key": "At3g61910"}, {"db": "GENBANK", "key": "At1g32770"}, {"db": "GENBANK", "key": "At5g12870"}, {"db": "GENBANK", "key": "At3g08500"}, {"db": "GENBANK", "key": "At1g16490"}, {"db": "GENBANK", "key": "At1g79180"}, {"db": "GENBANK", "key": "At4g22680"}, {"db": "GENBANK", "key": "At1g09540"}, {"db": "GENBANK", "key": "At1g63910"}], "notes": [], "created": "2019-11-22T14:28:02.623Z", "modified": "2025-10-17T13:03:57.081Z"}, {"entity": "publication", "iuid": "804fe367d4ba45b59d3d3ed95177e766", "links": {"self": {"href": "https://publications.scilifelab.se/publication/804fe367d4ba45b59d3d3ed95177e766.json"}, "display": {"href": "https://publications.scilifelab.se/publication/804fe367d4ba45b59d3d3ed95177e766"}}, "title": "Overexpression of chromatin remodeling and tyrosine kinase genes in iAMP21-positive acute lymphoblastic leukemia.", "authors": [{"family": "Ivanov \u00d6fverholm", "given": "Ingegerd", "initials": "I", "orcid": "0000-0002-6907-8004", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ba94eeea4d24e9c8c354fe1256fd0ce.json"}}, {"family": "Zachariadis", "given": "Vasilios", "initials": "V", "orcid": "0000-0001-9360-9859", "researcher": {"href": "https://publications.scilifelab.se/researcher/0607f2b65c12492cb30fb7a445d37937.json"}}, {"family": "Taylan", "given": "Fulya", "initials": "F", "orcid": "0000-0002-2907-0235", "researcher": {"href": "https://publications.scilifelab.se/researcher/c250909cc40f42ff9d6e2f640d12451b.json"}}, {"family": "Marincevic-Zuniga", "given": "Yanara", "initials": "Y", "orcid": "0000-0001-5576-2115", "researcher": {"href": "https://publications.scilifelab.se/researcher/eb045b70f16140b6b6e69476d701012c.json"}}, {"family": "Tran", "given": "Anh Nhi", "initials": "AN"}, {"family": "Saft", "given": "Leonie", "initials": "L"}, {"family": "Nilsson", "given": "Daniel", "initials": "D", "orcid": "0000-0001-5831-385X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b3f854e51704270831e155518265ea6.json"}}, {"family": "Syv\u00e4nen", "given": "Ann-Christine", "initials": "AC", "orcid": "0000-0002-9681-9146", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7012e35025543379380cb90efd71243.json"}}, {"family": "L\u00f6nnerholm", "given": "Gudmar", "initials": "G"}, {"family": "Harila-Saari", "given": "Arja", "initials": "A"}, {"family": "Nordenskj\u00f6ld", "given": "Magnus", "initials": "M", "orcid": "0000-0002-4974-425X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9f9dec008f1b42868dd133e9a396c968.json"}}, {"family": "Heyman", "given": "Mats", "initials": "M"}, {"family": "Nordgren", "given": "Ann", "initials": "A", "orcid": "0000-0003-3285-4281", "researcher": {"href": "https://publications.scilifelab.se/researcher/08e74c6ddc27493696beca0883027cdd.json"}}, {"family": "Nordlund", "given": "Jessica", "initials": "J", "orcid": "0000-0001-8699-9959", "researcher": {"href": "https://publications.scilifelab.se/researcher/ddf48c9262134821bcc6ce1180049753.json"}}, {"family": "Barbany", "given": "Gisela", "initials": "G"}], "type": "journal article", "published": "2020-03-00", "journal": {"title": "Leuk. Lymphoma", "issn": "1029-2403", "issn-l": "1026-8022", "volume": "61", "issue": "3", "pages": "604-613"}, "abstract": "Intrachromosomal amplification of chromosome 21 (iAMP21) is a cytogenetic subtype associated with relapse and poor prognosis in pediatric B-cell precursor acute lymphoblastic leukemia (BCP ALL). The biology behind the high relapse risk is unknown and the aim of this study was to further characterize the genomic and transcriptional landscape of iAMP21. Using DNA arrays and sequencing, we could identify rearrangements and aberrations characteristic for iAMP21. RNA sequencing revealed that only half of the genes in the minimal region of amplification (20/45) were differentially expressed in iAMP21. Among them were the top overexpressed genes (p < 0.001) in iAMP21 vs. BCP ALL without iAMP21 and three candidate genes could be identified, the tyrosine kinase gene DYRK1A and chromatin remodeling genes CHAF1B and SON. While overexpression of DYRK1A and CHAF1B is associated with poor prognosis in malignant diseases including myeloid leukemia, this is the first study to show significant correlation with iAMP21-positive ALL.", "doi": "10.1080/10428194.2019.1678153", "pmid": "31640433", "labels": {"National Genomics Infrastructure": "Collaborative", "NGI Uppsala (SNP&SEQ Technology Platform)": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [], "notes": [], "created": "2019-12-03T10:45:21.445Z", "modified": "2024-01-16T13:48:42.841Z"}, {"entity": "publication", "iuid": "b5443abd00b749b6ae6e72151a971b87", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b5443abd00b749b6ae6e72151a971b87.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b5443abd00b749b6ae6e72151a971b87"}}, "title": "Longitudinal changes in the frequency of mosaic chromosome Y loss in peripheral blood cells of aging men varies profoundly between individuals.", "authors": [{"family": "Danielsson", "given": "Marcus", "initials": "M", "orcid": "0000-0003-4418-0165", "researcher": {"href": "https://publications.scilifelab.se/researcher/d6b237ce613e4ef8a6d7ab2654c2c41e.json"}}, {"family": "Halvardson", "given": "Jonatan", "initials": "J"}, {"family": "Davies", "given": "Hanna", "initials": "H"}, {"family": "Torabi Moghadam", "given": "Behrooz", "initials": "B"}, {"family": "Mattisson", "given": "Jonas", "initials": "J", "orcid": "0000-0002-4456-9667", "researcher": {"href": "https://publications.scilifelab.se/researcher/2672b9fa599b44a395d1a2f8f59a5949.json"}}, {"family": "Rychlicka-Buniowska", "given": "Edyta", "initials": "E"}, {"family": "Jaszczy\u0144ski", "given": "Janusz", "initials": "J"}, {"family": "Heintz", "given": "Julia", "initials": "J"}, {"family": "Lannfelt", "given": "Lars", "initials": "L"}, {"family": "Giedraitis", "given": "Vilmantas", "initials": "V"}, {"family": "Ingelsson", "given": "Martin", "initials": "M"}, {"family": "Dumanski", "given": "Jan P", "initials": "JP"}, {"family": "Forsberg", "given": "Lars A", "initials": "LA", "orcid": "0000-0002-1701-755X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9ac2d8e983764a82982118b6db84029e.json"}}], "type": "journal article", "published": "2020-03-00", "journal": {"title": "Eur. J. Hum. Genet.", "issn": "1476-5438", "issn-l": "1018-4813", "volume": "28", "issue": "3", "pages": "349-357"}, "abstract": "Mosaic loss of chromosome Y (LOY) is the most common somatic genetic aberration and is associated with increased risk for all-cause mortality, various forms of cancer and Alzheimer's disease, as well as other common human diseases. By tracking LOY frequencies in subjects from which blood samples have been serially collected up to five times during up to 22 years, we observed a pronounced intra-individual variation of changes in the frequency of LOY within individual men over time. We observed that in some individuals the frequency of LOY in blood clearly progressed over time and that in other men, the frequency was constant or showed other types of longitudinal development. The predominant method used for estimating LOY is calculation of the median Log R Ratio of probes located in the male specific part of chromosome Y (mLRRY) from intensity data generated by SNP-arrays, which is difficult to interpret due to its logarithmic and inversed scale. We present here a formula to transform mLRRY-values to percentage of LOY that is a more comprehensible unit. The formula was derived using measurements of LOY from matched samples analysed using SNP-array, whole genome sequencing and a new AMELX/AMELY-based assay for droplet digital PCR. The methods described could be applied for analyses of the vast amount of SNP-array data already generated in the scientific community, allowing further discoveries of LOY associated diseases and outcomes.", "doi": "10.1038/s41431-019-0533-z", "pmid": "31654039", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41431-019-0533-z"}, {"db": "pmc", "key": "PMC7028735"}], "notes": [], "created": "2019-10-30T13:13:11.626Z", "modified": "2024-01-16T13:48:42.853Z"}, {"entity": "publication", "iuid": "5f926bdd219e419880e434267d225d2d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5f926bdd219e419880e434267d225d2d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5f926bdd219e419880e434267d225d2d"}}, "title": "Irreversible TrxR1 inhibitors block STAT3 activity and induce cancer cell death.", "authors": [{"family": "Busker", "given": "S", "initials": "S", "orcid": "0000-0002-7069-3864", "researcher": {"href": "https://publications.scilifelab.se/researcher/78029e78072548688bf306c577738232.json"}}, {"family": "Qian", "given": "W", "initials": "W"}, {"family": "Haraldsson", "given": "M", "initials": "M"}, {"family": "Espinosa", "given": "B", "initials": "B"}, {"family": "Johansson", "given": "L", "initials": "L"}, {"family": "Attarha", "given": "S", "initials": "S", "orcid": "0000-0003-4085-9680", "researcher": {"href": "https://publications.scilifelab.se/researcher/0095bacd15234e8488ecc6056ce0883e.json"}}, {"family": "Kolosenko", "given": "I", "initials": "I"}, {"family": "Liu", "given": "J", "initials": "J"}, {"family": "Dagnell", "given": "M", "initials": "M", "orcid": "0000-0002-5925-6794", "researcher": {"href": "https://publications.scilifelab.se/researcher/c36a6602bc714b878fd34f1f32f65672.json"}}, {"family": "Grand\u00e9r", "given": "D", "initials": "D"}, {"family": "Arn\u00e9r", "given": "E S J", "initials": "ESJ", "orcid": "0000-0002-4807-6114", "researcher": {"href": "https://publications.scilifelab.se/researcher/70a545effced47da8a5192a7472ceb8f.json"}}, {"family": "Tamm", "given": "K Pokrovskaja", "initials": "KP", "orcid": "0000-0001-6359-1256", "researcher": {"href": "https://publications.scilifelab.se/researcher/09ec3ee706764024bd748c7a77443845.json"}}, {"family": "Page", "given": "B D G", "initials": "BDG", "orcid": "0000-0002-2101-1329", "researcher": {"href": "https://publications.scilifelab.se/researcher/87dde8251a714d26b3b7cc045b47061f.json"}}], "type": "journal article", "published": "2020-03-00", "journal": {"title": "Sci Adv", "issn": "2375-2548", "volume": "6", "issue": "12", "pages": "eaax7945", "issn-l": "2375-2548"}, "abstract": "Because of its key role in cancer development and progression, STAT3 has become an attractive target for developing new cancer therapeutics. While several STAT3 inhibitors have progressed to advanced stages of development, their underlying biology and mechanisms of action are often more complex than would be expected from specific binding to STAT3. Here, we have identified and optimized a series of compounds that block STAT3-dependent luciferase expression with nanomolar potency. Unexpectedly, our lead compounds did not bind to cellular STAT3 but to another prominent anticancer drug target, TrxR1. We further identified that TrxR1 inhibition induced Prx2 and STAT3 oxidation, which subsequently blocked STAT3-dependent transcription. Moreover, previously identified inhibitors of STAT3 were also found to inhibit TrxR1, and likewise, established TrxR1 inhibitors block STAT3-dependent transcriptional activity. These results provide new insights into the complexities of STAT3 redox regulation while highlighting a novel mechanism to block aberrant STAT3 signaling in cancer cells.", "doi": "10.1126/sciadv.aax7945", "pmid": "32219156", "labels": {"Protein Science Facility (PSF)": "Service", "Chemical Biology Consortium Sweden": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC7083616"}, {"db": "pii", "key": "aax7945"}], "notes": [], "created": "2020-09-25T11:19:23.210Z", "modified": "2025-10-17T13:04:28.359Z"}, {"entity": "publication", "iuid": "845b1779f6ea403fa9951ec2d234f8e1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/845b1779f6ea403fa9951ec2d234f8e1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/845b1779f6ea403fa9951ec2d234f8e1"}}, "title": "In Situ Encapsulation of Nile Red or Doxorubicin during RAFT\u2010Mediated Emulsion Polymerization via Polymerization\u2010Induced Self\u2010Assembly for Biomedical Applications", "authors": [{"family": "Engstr\u00f6m", "given": "Joakim", "initials": "J"}, {"family": "Asem", "given": "Heba", "initials": "H", "orcid": "0000-0001-8887-9141", "researcher": {"href": "https://publications.scilifelab.se/researcher/f778f5b9721649ca9ae8207c7adb6ceb.json"}}, {"family": "Brismar", "given": "Hjalmar", "initials": "H", "orcid": "0000-0003-0578-4003", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ec23336e2ef4e298f340876f1136dce.json"}}, {"family": "Zhang", "given": "Yuning", "initials": "Y"}, {"family": "Malkoch", "given": "Michael", "initials": "M"}, {"family": "Malmstr\u00f6m", "given": "Eva", "initials": "E", "orcid": "0000-0002-8348-2273", "researcher": {"href": "https://publications.scilifelab.se/researcher/9fb8e9a4e33d4fc7897b9dec2045a35b.json"}}], "type": "journal-article", "published": "2020-03-00", "journal": {"title": "Macromol. Chem. Phys.", "issn": "1022-1352", "volume": "221", "issue": "5", "pages": "1900443", "issn-l": null}, "abstract": null, "doi": "10.1002/macp.201900443", "pmid": null, "labels": {"Integrated Microscopy Technologies Stockholm": "Service"}, "xrefs": [], "notes": [], "created": "2020-12-10T21:31:20.763Z", "modified": "2021-11-10T12:41:34.446Z"}, {"entity": "publication", "iuid": "4c85c4f3e9624ded9b910cee95bfc2b8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4c85c4f3e9624ded9b910cee95bfc2b8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4c85c4f3e9624ded9b910cee95bfc2b8"}}, "title": "Hyena paleogenomes reveal a complex evolutionary history of cross-continental gene flow between spotted and cave hyena.", "authors": [{"family": "Westbury", "given": "Michael V", "initials": "MV", "orcid": "0000-0003-0478-3930", "researcher": {"href": "https://publications.scilifelab.se/researcher/0c4a764072a0474abe4ca97c7b220676.json"}}, {"family": "Hartmann", "given": "Stefanie", "initials": "S"}, {"family": "Barlow", "given": "Axel", "initials": "A"}, {"family": "Preick", "given": "Michaela", "initials": "M"}, {"family": "Ridush", "given": "Bogdan", "initials": "B", "orcid": "0000-0002-5896-6073", "researcher": {"href": "https://publications.scilifelab.se/researcher/4615423b4a504bdcbfc76429f38b48ea.json"}}, {"family": "Nagel", "given": "Doris", "initials": "D"}, {"family": "Rathgeber", "given": "Thomas", "initials": "T", "orcid": "0000-0001-6549-6543", "researcher": {"href": "https://publications.scilifelab.se/researcher/39c4006697bf419ba19fa020e80de5c4.json"}}, {"family": "Ziegler", "given": "Reinhard", "initials": "R"}, {"family": "Baryshnikov", "given": "Gennady", "initials": "G"}, {"family": "Sheng", "given": "Guilian", "initials": "G", "orcid": "0000-0003-2314-1650", "researcher": {"href": "https://publications.scilifelab.se/researcher/e96cf70da0364db0926d5312a9076a97.json"}}, {"family": "Ludwig", "given": "Arne", "initials": "A", "orcid": "0000-0001-7249-9953", "researcher": {"href": "https://publications.scilifelab.se/researcher/d5bba6af461445c7bd4a2b6ee97bbd2e.json"}}, {"family": "Wiesel", "given": "Ingrid", "initials": "I"}, {"family": "Dalen", "given": "Love", "initials": "L", "orcid": "0000-0001-8270-7613", "researcher": {"href": "https://publications.scilifelab.se/researcher/48ecf726779249ac9d12f4f7a1cc62bf.json"}}, {"family": "Bibi", "given": "Faysal", "initials": "F", "orcid": "0000-0002-9414-5547", "researcher": {"href": "https://publications.scilifelab.se/researcher/ac6a6d03a0c440328ca1a58fd70cf0f3.json"}}, {"family": "Werdelin", "given": "Lars", "initials": "L"}, {"family": "Heller", "given": "Rasmus", "initials": "R", "orcid": "0000-0001-6583-6923", "researcher": {"href": "https://publications.scilifelab.se/researcher/0289add03723441ab92592b4e3702a2c.json"}}, {"family": "Hofreiter", "given": "Michael", "initials": "M"}], "type": "journal article", "published": "2020-03-00", "journal": {"title": "Sci Adv", "issn": "2375-2548", "volume": "6", "issue": "11", "pages": "eaay0456", "issn-l": "2375-2548"}, "abstract": "The genus Crocuta (African spotted and Eurasian cave hyenas) includes several closely related extinct and extant lineages. The relationships among these lineages, however, are contentious. Through the generation of population-level paleogenomes from late Pleistocene Eurasian cave hyena and genomes from modern African spotted hyena, we reveal the cross-continental evolutionary relationships between these enigmatic hyena lineages. We find a deep divergence (~2.5 Ma) between African and Eurasian Crocuta populations, suggesting that ancestral Crocuta left Africa around the same time as early Homo. Moreover, we find discordance between nuclear and mitochondrial phylogenies and evidence for bidirectional gene flow between African and Eurasian Crocuta after the lineages split, which may have complicated prior taxonomic classifications. Last, we find a number of introgressed loci that attained high frequencies within the recipient lineage, suggesting some level of adaptive advantage from admixture.", "doi": "10.1126/sciadv.aay0456", "pmid": "32201717", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service"}, "xrefs": [{"db": "pii", "key": "aay0456"}, {"db": "pmc", "key": "PMC7069707"}], "notes": [], "created": "2020-07-08T13:04:56.878Z", "modified": "2021-11-10T12:53:35.972Z"}, {"entity": "publication", "iuid": "a5dc2e45a1f5491ca43a9380cf38b99a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a5dc2e45a1f5491ca43a9380cf38b99a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a5dc2e45a1f5491ca43a9380cf38b99a"}}, "title": "High genetic risk score is associated with early disease onset, damage accrual and decreased survival in systemic lupus erythematosus.", "authors": [{"family": "Reid", "given": "Sarah", "initials": "S", "orcid": "0000-0003-4065-6875", "researcher": {"href": "https://publications.scilifelab.se/researcher/689ab046bc19433483d502284d2c51c4.json"}}, {"family": "Alexsson", "given": "Andrei", "initials": "A"}, {"family": "Frodlund", "given": "Martina", "initials": "M"}, {"family": "Morris", "given": "David", "initials": "D"}, {"family": "Sandling", "given": "Johanna K", "initials": "JK"}, {"family": "Bolin", "given": "Karin", "initials": "K"}, {"family": "Svenungsson", "given": "Elisabet", "initials": "E", "orcid": "0000-0003-3396-3244", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ab5989c3c604a96bf42b1b6f90434a0.json"}}, {"family": "J\u00f6nsen", "given": "Andreas", "initials": "A"}, {"family": "Bengtsson", "given": "Christine", "initials": "C"}, {"family": "Gunnarsson", "given": "Iva", "initials": "I"}, {"family": "Illescas Rodriguez", "given": "Vera", "initials": "V"}, {"family": "Bengtsson", "given": "Anders", "initials": "A"}, {"family": "Arve", "given": "Sabine", "initials": "S", "orcid": "0000-0002-3347-5550", "researcher": {"href": "https://publications.scilifelab.se/researcher/b64a9ba6c7d344d0a47ef99532a347ab.json"}}, {"family": "Rantap\u00e4\u00e4-Dahlqvist", "given": "Solbritt", "initials": "S", "orcid": "0000-0001-8259-3863", "researcher": {"href": "https://publications.scilifelab.se/researcher/dfca4bfdcf3946fda64397d3b7debc59.json"}}, {"family": "Eloranta", "given": "Maija-Leena", "initials": "ML"}, {"family": "Syv\u00e4nen", "given": "Ann-Christine", "initials": "AC", "orcid": "0000-0002-9681-9146", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7012e35025543379380cb90efd71243.json"}}, {"family": "Sj\u00f6wall", "given": "Christopher", "initials": "C", "orcid": "0000-0003-0900-2048", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe4dd47b8ca1436e8a26fdea33f5e7f6.json"}}, {"family": "Vyse", "given": "Timothy James", "initials": "TJ"}, {"family": "R\u00f6nnblom", "given": "Lars", "initials": "L", "orcid": "0000-0001-9403-6503", "researcher": {"href": "https://publications.scilifelab.se/researcher/053ed3b657124a1bab3a78dc685556e6.json"}}, {"family": "Leonard", "given": "Dag", "initials": "D", "orcid": "0000-0002-6275-7282", "researcher": {"href": "https://publications.scilifelab.se/researcher/42ed25c2f495484db4757f4fef51abae.json"}}], "type": "journal article", "published": "2020-03-00", "journal": {"title": "Ann. Rheum. Dis.", "issn": "1468-2060", "issn-l": "0003-4967", "volume": "79", "issue": "3", "pages": "363-369"}, "abstract": "To investigate associations between a high genetic disease risk and disease severity in patients with systemic lupus erythematosus (SLE).\n\nPatients with SLE (n=1001, discovery cohort and n=5524, replication cohort) and healthy controls (n=2802 and n=9859) were genotyped using a 200K Immunochip single nucleotide polymorphism array. A genetic risk score (GRS) was assigned to each individual based on 57 SLE risk loci.\n\nSLE was more prevalent in the high, compared with the low, GRS-quartile (OR 12.32 (9.53 to 15.71), p=7.9\u00d710-86 and OR 7.48 (6.73 to 8.32), p=2.2\u00d710-304 for the discovery and the replication cohorts, respectively). In the discovery cohort, patients in the high GRS-quartile had a 6-year earlier mean disease onset (HR 1.47 (1.22 to 1.75), p=4.3\u00d710-5), displayed higher prevalence of damage accrual (OR 1.47 (1.06 to 2.04), p=2.0\u00d710-2), renal disorder (OR 2.22 (1.50 to 3.27), p=5.9\u00d710-5), anti-dsDNA (OR 1.83 (1.19 to 2.81), p=6.1\u00d710-3), end-stage renal disease (ESRD) (OR 5.58 (1.50 to 20.79), p=1.0\u00d710-2), proliferative nephritis (OR 2.42 (1.30 to 4.49), p=5.1\u00d710-3), anti-cardiolipin-IgG (OR 1.89 (1.13 to 3.18), p=1.6\u00d710-2), anti-\u03b22-glycoprotein-I-IgG (OR 2.29 (1.29 to 4.06), p=4.8\u00d710-3) and positive lupus anticoagulant test (OR 2.12 (1.16 to 3.89), p=1.5\u00d710-2) compared with patients in the low GRS-quartile. Survival analysis showed earlier onset of the first organ damage (HR 1.51 (1.04 to 2.25), p=3.7\u00d710-2), first cardiovascular event (HR 1.65 (1.03 to 2.64), p=2.6\u00d710-2), nephritis (HR 2.53 (1.72 to 3.71), p=9.6\u00d710-7), ESRD (HR 6.78 (1.78 to 26.86), p=6.5\u00d710-3) and decreased overall survival (HR 1.83 (1.02 to 3.30), p=4.3\u00d710-2) in high to low quartile comparison.\n\nA high GRS is associated with increased risk of organ damage, renal dysfunction and all-cause mortality. Our results indicate that genetic profiling may be useful for predicting outcomes in patients with SLE.", "doi": "10.1136/annrheumdis-2019-216227", "pmid": "31826855", "labels": {"National Genomics Infrastructure": "Collaborative", "NGI Uppsala (SNP&SEQ Technology Platform)": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "annrheumdis-2019-216227"}, {"db": "pmc", "key": "PMC7034364"}], "notes": [], "created": "2019-12-18T16:32:05.276Z", "modified": "2024-01-16T13:48:42.863Z"}, {"entity": "publication", "iuid": "66acb228c0fe4207af5b7c2a2b3ad412", "links": {"self": {"href": "https://publications.scilifelab.se/publication/66acb228c0fe4207af5b7c2a2b3ad412.json"}, "display": {"href": "https://publications.scilifelab.se/publication/66acb228c0fe4207af5b7c2a2b3ad412"}}, "title": "Heritability of Caries Scores, Trajectories, and Disease Subtypes.", "authors": [{"family": "Haworth", "given": "S", "initials": "S", "orcid": "0000-0001-7793-7326", "researcher": {"href": "https://publications.scilifelab.se/researcher/43fa9fb331c849b58d4ac4b14f04fbda.json"}}, {"family": "Esberg", "given": "A", "initials": "A", "orcid": "0000-0002-4430-8125", "researcher": {"href": "https://publications.scilifelab.se/researcher/a6610f154ad749a49a8f5d89382c6b1b.json"}}, {"family": "Lif Holgerson", "given": "P", "initials": "P"}, {"family": "Kuja-Halkola", "given": "R", "initials": "R"}, {"family": "Timpson", "given": "N J", "initials": "NJ"}, {"family": "Magnusson", "given": "P K E", "initials": "PKE"}, {"family": "Franks", "given": "P W", "initials": "PW"}, {"family": "Johansson", "given": "I", "initials": "I"}], "type": "journal article", "published": "2020-03-00", "journal": {"title": "J Dent Res", "issn": "0022-0345", "volume": "99", "issue": "3", "pages": "264-270", "issn-l": null}, "abstract": "Previous studies report that dental caries is partially heritable, but there is uncertainty in the magnitude of genetic effects and little understanding of how genetic factors might influence caries progression or caries subtypes. This study aimed to estimate the relative importance of genetic and environmental factors in the etiology of different caries outcomes using a twin-based design. Analysis included up to 41,678 twins in the Swedish Twin Register aged 7 to 97 y, and dental data were obtained from preexisting dental records. The outcome measures were 1) summary indices of caries experience, 2) parameters representing trajectory in caries progression derived from longitudinal modeling, and 3) caries scores in groups of biologically similar tooth surfaces derived from hierarchical clustering of tooth surfaces (termed caries clusters). Additive genetic factors explained between 49.1% and 62.7% of variation in caries scores and between 50.0% and 60.5% of variation in caries trajectories. Seven caries clusters were identified, which had estimates of heritability lying between 41.9% and 54.3%. Shared environmental factors were important for only some of these clusters and explained 16% of variation in fissure caries in molar teeth but little variation in other clusters of caries presentation. The genetic factors influencing these clusters were only partially overlapping, suggesting that different biological processes are important in different groups of tooth surfaces and that innate liability to some patterns of caries presentation may partially explain why groups of tooth surfaces form clusters within the mouth. These results provide 1) improved quantification of genetic factors in the etiology of caries and 2) new data about the role of genetics in terms of longitudinal changes in caries status and specific patterns of disease presentation, and they may help lay the foundations for personalized interventions in the future.", "doi": "10.1177/0022034519897910", "pmid": "31905308", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7036480"}], "notes": [], "created": "2021-01-07T17:01:45.040Z", "modified": "2021-12-07T13:55:12.669Z"}, {"entity": "publication", "iuid": "30a54de97a514ce29242a464f143a6f9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/30a54de97a514ce29242a464f143a6f9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/30a54de97a514ce29242a464f143a6f9"}}, "title": "Functionally distinct subgroups of oligodendrocyte precursor cells integrate neural activity and execute myelin formation.", "authors": [{"family": "Marisca", "given": "Roberta", "initials": "R"}, {"family": "Hoche", "given": "Tobias", "initials": "T"}, {"family": "Agirre", "given": "Eneritz", "initials": "E", "orcid": "0000-0002-5012-0305", "researcher": {"href": "https://publications.scilifelab.se/researcher/a507b19745c64c3bb8ef5dce800c8687.json"}}, {"family": "Hoodless", "given": "Laura Jane", "initials": "LJ"}, {"family": "Barkey", "given": "Wenke", "initials": "W"}, {"family": "Auer", "given": "Franziska", "initials": "F"}, {"family": "Castelo-Branco", "given": "Gon\u00e7alo", "initials": "G", "orcid": "0000-0003-2247-9393", "researcher": {"href": "https://publications.scilifelab.se/researcher/10b1a8fb48114340b8e390ca1f9e3321.json"}}, {"family": "Czopka", "given": "Tim", "initials": "T", "orcid": "0000-0002-6824-8112", "researcher": {"href": "https://publications.scilifelab.se/researcher/9a9b1bd37a6a4ec2ac6b236795531d81.json"}}], "type": "journal article", "published": "2020-03-00", "journal": {"title": "Nat. Neurosci.", "issn": "1546-1726", "volume": "23", "issue": "3", "pages": "363-374", "issn-l": "1097-6256"}, "abstract": "Recent reports have revealed that oligodendrocyte precursor cells (OPCs) are heterogeneous. It remains unclear whether such heterogeneity reflects different subtypes of cells with distinct functions or instead reflects transiently acquired states of cells with the same function. By integrating lineage formation of individual OPC clones, single-cell transcriptomics, calcium imaging and neural activity manipulation, we show that OPCs in the zebrafish spinal cord can be divided into two functionally distinct groups. One subgroup forms elaborate networks of processes and exhibits a high degree of calcium signaling, but infrequently differentiates despite contact with permissive axons. Instead, these OPCs divide in an activity- and calcium-dependent manner to produce another subgroup, with higher process motility and less calcium signaling and that readily differentiates. Our data show that OPC subgroups are functionally diverse in their response to neurons and that activity regulates the proliferation of a subset of OPCs that is distinct from the cells that generate differentiated oligodendrocytes.", "doi": "10.1038/s41593-019-0581-2", "pmid": "32066987", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41593-019-0581-2"}, {"db": "pmc", "key": "PMC7292734"}, {"db": "mid", "key": "EMS85307"}], "notes": [], "created": "2020-07-08T13:05:15.850Z", "modified": "2024-01-16T13:48:42.870Z"}, {"entity": "publication", "iuid": "c9b0fa4d11e0486c8d7898eeebfe293a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c9b0fa4d11e0486c8d7898eeebfe293a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c9b0fa4d11e0486c8d7898eeebfe293a"}}, "title": "Evidence for widespread selection in shaping the genomic landscape during speciation of Populus.", "authors": [{"family": "Wang", "given": "Jing", "initials": "J", "orcid": "0000-0002-3793-3264", "researcher": {"href": "https://publications.scilifelab.se/researcher/98818d7f0b9c48088fdb7109ba037f54.json"}}, {"family": "Street", "given": "Nathaniel R", "initials": "NR"}, {"family": "Park", "given": "Eung-Jun", "initials": "EJ"}, {"family": "Liu", "given": "Jianquan", "initials": "J"}, {"family": "Ingvarsson", "given": "P\u00e4r K", "initials": "PK", "orcid": "0000-0001-9225-7521", "researcher": {"href": "https://publications.scilifelab.se/researcher/52a2c210ff754465a69f839b40fe8312.json"}}], "type": "journal article", "published": "2020-03-00", "journal": {"title": "Mol. Ecol.", "issn": "1365-294X", "volume": "29", "issue": "6", "pages": "1120-1136", "issn-l": "0962-1083"}, "abstract": "Increasing our understanding of how evolutionary processes drive the genomic landscape of variation is fundamental to a better understanding of the genomic consequences of speciation. However, genome-wide patterns of within- and between- species variation have not been fully investigated in most forest tree species despite their global ecological and economic importance. Here, we use whole-genome resequencing data from four Populus species spanning the speciation continuum to reconstruct their demographic histories and investigate patterns of diversity and divergence within and between species. Using Populus trichocarpa as an outgroup species, we further infer the genealogical relationships and estimate the extent of ancient introgression among the three aspen species (Populus tremula, Populus davidiana and Populus tremuloides) throughout the genome. Our results show substantial variation in these patterns along the genomes with this variation being strongly predicted by local recombination rates and the density of functional elements. This implies that the interaction between recurrent selection and intrinsic genomic features has dramatically sculpted the genomic landscape over long periods of time. In addition, our findings provide evidence that, apart from background selection, recent positive selection and long-term balancing selection have also been crucial components in shaping patterns of genome-wide variation during the speciation process.", "doi": "10.1111/mec.15388", "pmid": "32068935", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "GENBANK", "key": "PRJNA576115"}], "notes": [], "created": "2020-07-08T13:03:45.321Z", "modified": "2024-01-16T13:48:42.878Z"}, {"entity": "publication", "iuid": "b7650f46ca4f4c56a430894a420c5bb3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b7650f46ca4f4c56a430894a420c5bb3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b7650f46ca4f4c56a430894a420c5bb3"}}, "title": "Distinct structural modulation of photosystem I and lipid environment stabilizes its tetrameric assembly.", "authors": [{"family": "Chen", "given": "Ming", "initials": "M"}, {"family": "Perez-Boerema", "given": "Annemarie", "initials": "A", "orcid": "0000-0002-1180-5838", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a711071c6844bdcb4c151971774435f.json"}}, {"family": "Zhang", "given": "Laixing", "initials": "L", "orcid": "0000-0001-9552-3848", "researcher": {"href": "https://publications.scilifelab.se/researcher/e60e16efc7454a6ebdf8697e9f51a03b.json"}}, {"family": "Li", "given": "Yanxue", "initials": "Y"}, {"family": "Yang", "given": "Maojun", "initials": "M", "orcid": "0000-0002-6798-3094", "researcher": {"href": "https://publications.scilifelab.se/researcher/e2e4673b1b6f484990b2818076942f61.json"}}, {"family": "Li", "given": "Shizhong", "initials": "S", "orcid": "0000-0001-9605-1109", "researcher": {"href": "https://publications.scilifelab.se/researcher/df1330d71677410887cc6dcb0186355f.json"}}, {"family": "Amunts", "given": "Alexey", "initials": "A", "orcid": "0000-0002-5302-1740", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7d0bf36ad1a47f5b5b88f78d1e15395.json"}}], "type": "journal article", "published": "2020-03-00", "journal": {"volume": "6", "issn": "2055-0278", "issue": "3", "pages": "314-320", "title": "NPLANTS", "issn-l": "2055-0278"}, "abstract": "Photosystem I (PSI) is able to form different oligomeric states across various species. To reveal the structural basis for PSI dimerization and tetramerization, we structurally investigated PSI from the cyanobacterium Anabaena. This revealed a disrupted trimerization domain due to lack of the terminal residues of PsaL in the lumen, which resulted in PSI dimers with loose connections between monomers and weaker energy-coupled chlorophylls than in the trimer. At the dimer surface, specific phospholipids, cofactors and interactions in combination facilitated recruitment of another dimer to form a tetramer. Taken together, the relaxed luminal connections and lipid specificity at the dimer interface account for membrane curvature. PSI tetramer assembly appears to increase the surface area of the thylakoid membrane, which would contribute to PSI crowding.", "doi": "10.1038/s41477-020-0610-x", "pmid": "32170279", "labels": {"Cryo-EM": "Service", "Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41477-020-0610-x"}], "notes": [], "created": "2020-03-10T11:55:25.538Z", "modified": "2021-11-10T12:53:09.684Z"}, {"entity": "publication", "iuid": "f603d9d298dc4c11ab66784e73e88159", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f603d9d298dc4c11ab66784e73e88159.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f603d9d298dc4c11ab66784e73e88159"}}, "title": "Discovery of Species-unique Peptide Biomarkers of Bacterial Pathogens by Tandem Mass Spectrometry-based Proteotyping.", "authors": [{"family": "Karlsson", "given": "Roger", "initials": "R", "orcid": "0000-0002-5919-2639", "researcher": {"href": "https://publications.scilifelab.se/researcher/bd9b10fd0fa34dd9a3de96f3c4860e32.json"}}, {"family": "Thorsell", "given": "Annika", "initials": "A"}, {"family": "Gomila", "given": "Margarita", "initials": "M"}, {"family": "Salv\u00e0-Serra", "given": "Francisco", "initials": "F"}, {"family": "Jakobsson", "given": "Hedvig E", "initials": "HE"}, {"family": "Gonzales-Siles", "given": "Lucia", "initials": "L"}, {"family": "Ja\u00e9n-Luchoro", "given": "Daniel", "initials": "D"}, {"family": "Skovbjerg", "given": "Susann", "initials": "S"}, {"family": "Fuchs", "given": "Johannes", "initials": "J", "orcid": "0000-0001-9317-6969", "researcher": {"href": "https://publications.scilifelab.se/researcher/65bf045dd14e45a4b61b4eb36e979bc0.json"}}, {"family": "Karlsson", "given": "Anders", "initials": "A"}, {"family": "Boulund", "given": "Fredrik", "initials": "F"}, {"family": "Johnning", "given": "Anna", "initials": "A"}, {"family": "Kristiansson", "given": "Erik", "initials": "E"}, {"family": "Moore", "given": "Edward R B", "initials": "ERB"}], "type": "journal article", "published": "2020-03-00", "journal": {"title": "Mol. Cell Proteomics", "issn": "1535-9484", "volume": "19", "issue": "3", "pages": "518-528", "issn-l": "1535-9476"}, "abstract": "Mass spectrometry (MS) and proteomics offer comprehensive characterization and identification of microorganisms and discovery of protein biomarkers that are applicable for diagnostics of infectious diseases. The use of biomarkers for diagnostics is widely applied in the clinic and the use of peptide biomarkers is increasingly being investigated for applications in the clinical laboratory. Respiratory-tract infections are a predominant cause for medical treatment, although, clinical assessments and standard clinical laboratory protocols are time-consuming and often inadequate for reliable diagnoses. Novel methods, preferably applied directly to clinical samples, excluding cultivation steps, are needed to improve diagnostics of infectious diseases, provide adequate treatment and reduce the use of antibiotics and associated development of antibiotic resistance. This study applied nano-liquid chromatography (LC) coupled with tandem MS, with a bioinformatics pipeline and an in-house database of curated high-quality reference genome sequences to identify species-unique peptides as potential biomarkers for four bacterial pathogens commonly found in respiratory tract infections (RTIs): Staphylococcus aureus; Moraxella catarrhalis; Haemophilus influenzae and Streptococcus pneumoniae The species-unique peptides were initially identified in pure cultures of bacterial reference strains, reflecting the genomic variation in the four species and, furthermore, in clinical respiratory tract samples, without prior cultivation, elucidating proteins expressed in clinical conditions of infection. For each of the four bacterial pathogens, the peptide biomarker candidates most predominantly found in clinical samples, are presented. Data are available via ProteomeXchange with identifier PXD014522. As proof-of-principle, the most promising species-unique peptides were applied in targeted tandem MS-analyses of clinical samples and their relevance for identifications of the pathogens, i.e. proteotyping, was validated, thus demonstrating their potential as peptide biomarker candidates for diagnostics of infectious diseases.", "doi": "10.1074/mcp.RA119.001667", "pmid": "31941798", "labels": {"Glycoproteomics and MS Proteomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S1535-9476(20)35038-6"}, {"db": "pmc", "key": "PMC7050107"}], "notes": [], "created": "2020-01-30T15:57:23.467Z", "modified": "2024-01-16T13:46:30.972Z"}, {"entity": "publication", "iuid": "36a139ec84d74001845f829037276801", "links": {"self": {"href": "https://publications.scilifelab.se/publication/36a139ec84d74001845f829037276801.json"}, "display": {"href": "https://publications.scilifelab.se/publication/36a139ec84d74001845f829037276801"}}, "title": "Chemical imaging of evolving amyloid plaque pathology and associated A\u03b2 peptide aggregation in a transgenic mouse model of Alzheimer's disease.", "authors": [{"family": "Michno", "given": "Wojciech", "initials": "W", "orcid": "0000-0002-3096-3604", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b4307eb6e45426e8176337e88c9c344.json"}}, {"family": "Wehrli", "given": "Patrick", "initials": "P"}, {"family": "Meier", "given": "Silvio R", "initials": "SR"}, {"family": "Sehlin", "given": "Dag", "initials": "D"}, {"family": "Syv\u00e4nen", "given": "Stina", "initials": "S"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H", "orcid": "0000-0003-3930-4354", "researcher": {"href": "https://publications.scilifelab.se/researcher/85efee74eb4a4b38b63cf2823d204529.json"}}, {"family": "Blennow", "given": "Kaj", "initials": "K"}, {"family": "Hanrieder", "given": "J\u00f6rg", "initials": "J", "orcid": "0000-0001-6059-198X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e65454100674f98bf8f2575093f2441.json"}}], "type": "journal article", "published": "2020-03-00", "journal": {"title": "J. Neurochem.", "issn": "1471-4159", "volume": "152", "issue": "5", "pages": "602-616", "issn-l": "0022-3042"}, "abstract": "One of the major hallmarks of Alzheimer's disease (AD) pathology is the formation of extracellular amyloid \u03b2 (A\u03b2) plaques. While A\u03b2 has been suggested to be critical in inducing and, potentially, driving the disease, the molecular basis of AD pathogenesis is still under debate. Extracellular A\u03b2 plaque pathology manifests itself upon aggregation of distinct A\u03b2 peptides, resulting in morphologically different plaque morphotypes, including mainly diffuse and cored senile plaques. As plaque pathology precipitates long before any clinical symptoms occur, targeting the A\u03b2 aggregation processes provides a promising target for early interventions. However, the chain of events of when, where and what A\u03b2 species aggregate and form plaques remains unclear. The aim of this study was to investigate the potential of matrix-assisted laser desorption/ionization imaging mass spectrometry as a tool to study the evolving pathology in transgenic mouse models for AD. To that end, we used an emerging, chemical imaging modality - matrix-assisted laser desorption/ionization imaging mass spectrometry - that allows for delineating A\u03b2 aggregation with specificity at the single plaque level. We identified that plaque formation occurs first in cortical regions and that these younger plaques contain higher levels of 42 amino acid-long A\u03b2 (A\u03b21-42). Plaque maturation was found to be characterized by a relative increase in deposition of A\u03b21-40, which was associated with the appearance of a cored morphology for those plaques. Finally, other C-terminally truncated A\u03b2 species (A\u03b21-38 and A\u03b21-39) exhibited a similar aggregation pattern as A\u03b21-40, suggesting that these species have similar aggregation characteristics. These results suggest that initial plaque formation is seeded by A\u03b21-42; a process that is followed by plaque maturation upon deposition of A\u03b21-40 as well as deposition of other C-terminally modified A\u03b2 species.", "doi": "10.1111/jnc.14888", "pmid": "31605538", "labels": {"Integrated Microscopy Technologies Gothenburg": "Collaborative"}, "xrefs": [], "notes": [], "created": "2023-02-16T08:08:09.467Z", "modified": "2023-02-16T08:12:11.343Z"}, {"entity": "publication", "iuid": "c54172d1718541a189d45d3515061a7f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c54172d1718541a189d45d3515061a7f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c54172d1718541a189d45d3515061a7f"}}, "title": "Apolipoprotein E impairs amyloid-\u03b2 fibril elongation and maturation.", "authors": [{"family": "Islam", "given": "Tohidul", "initials": "T"}, {"family": "Gharibyan", "given": "Anna L", "initials": "AL"}, {"family": "Golchin", "given": "Solmaz A", "initials": "SA"}, {"family": "Pettersson", "given": "Nina", "initials": "N"}, {"family": "Br\u00e4nnstr\u00f6m", "given": "Kristoffer", "initials": "K"}, {"family": "Hedberg", "given": "Isabell", "initials": "I"}, {"family": "Virta", "given": "Merit-Miriam", "initials": "MM"}, {"family": "Olofsson", "given": "Linnea", "initials": "L"}, {"family": "Olofsson", "given": "Anders", "initials": "A", "orcid": "0000-0002-8743-8720", "researcher": {"href": "https://publications.scilifelab.se/researcher/c4d7fc22bf3e4a39bd375ee0e31bca29.json"}}], "type": "journal article", "published": "2020-03-00", "journal": {"title": "FEBS J.", "issn": "1742-4658", "volume": "287", "issue": "6", "pages": "1208-1219", "issn-l": "1742-464X"}, "abstract": "Alzheimer's disease (AD) is strongly linked to amyloid depositions of the A\u03b2 peptide (A\u03b2). The lipid-binding protein apolipoprotein E (ApoE) has been found to interfere with A\u03b2 amyloid formation and to exert a strong clinical impact to the pathology of AD. The APOE gene exists in three allelic isoforms represented by APOE \u03b52, APOE \u03b53, and APOE \u03b54. Carriers of the APOE \u03b54 variant display a gene dose-dependent increased risk of developing the disease. A\u03b2 amyloids are formed via a nucleation-dependent mechanism where free monomers are added onto a nucleus in a template-dependent manner. Using a combination of surface plasmon resonance and thioflavin-T assays, we here show that ApoE can target the process of fibril elongation and that its interference effectively prevents amyloid maturation. We expose a complex equilibrium where the concentration of ApoE, A\u03b2 monomers, and the amount of already formed A\u03b2 fibrils will affect the relative proportion and formation rate of mature amyloids versus alternative assemblies. The result illustrates a mechanism which may affect both the clearance rate of A\u03b2 assemblies in vivo and the population of cytotoxic A\u03b2 assemblies.", "doi": "10.1111/febs.15075", "pmid": "31571352", "labels": {"Cryo-EM": "Service"}, "xrefs": [], "notes": [], "created": "2020-01-08T09:14:47.064Z", "modified": "2021-11-10T12:53:41.902Z"}, {"entity": "publication", "iuid": "1d494d4aae3148d6adc0f0e34b6fea33", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1d494d4aae3148d6adc0f0e34b6fea33.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1d494d4aae3148d6adc0f0e34b6fea33"}}, "title": "A link between the newly described colistin resistance gene mcr-9 and clinical Enterobacteriaceae isolates carrying blaSHV-12 from horses in Sweden.", "authors": [{"family": "B\u00f6rjesson", "given": "Stefan", "initials": "S", "orcid": "0000-0003-2219-2659", "researcher": {"href": "https://publications.scilifelab.se/researcher/e98c1d640f9a4eeaba4563eeec9e7dff.json"}}, {"family": "Greko", "given": "Christina", "initials": "C"}, {"family": "Myren\u00e5s", "given": "Mattias", "initials": "M"}, {"family": "Land\u00e9n", "given": "Annica", "initials": "A"}, {"family": "Nilsson", "given": "Oskar", "initials": "O"}, {"family": "Pedersen", "given": "Karl", "initials": "K"}], "type": "journal article", "published": "2020-03-00", "journal": {"title": "J Glob Antimicrob Resist", "issn": "2213-7173", "volume": "20", "issue": null, "pages": "285-289", "issn-l": "2213-7165"}, "abstract": "The aim of this study was to investigate the occurrence of the newly described transferable colistin resistance gene mcr-9 in extended-spectrum \u03b2-lactamase (ESBL)-producing clinical Enterobacteriaceae isolates from horses in Sweden.\n\nA total of 56 whole-genome sequenced ESBL-producing Enterobacteriaceae isolates from horses were subjected to in silico detection of antimicrobial resistance genes and identification of plasmid replicons types. The colistin minimum inhibitory concentration (MIC) for mcr-positive isolates was determined by broth microdilution. Relatedness between Enterobacteriaceae carrying mcr genes was determined by multilocus sequence typing (MLST) and core genome MLST.\n\nThirty ESBL-producing Enterobacteriaceae isolates from horses were positive for the colistin resistance gene mcr-9. These isolates included Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca and Citrobacter freundii and belonged to diverse MLST sequence types within each species. Two of the mcr-9-containing isolates originated from the same horse. All mcr-9-positive isolates had colistin MICs below or equal to the EUCAST epidemiological cut-off value of 2 mg/L and were negative for the two potential regulatory genes qseB-like and qseC-like for mcr-9. Except for one isolate carrying only blaTEM-1B, all of the isolates carried blaSHV-12 and blaTEM-1B, and were all considered multidrug-resistant as they harboured genes encoding resistance to aminoglycosides, chloramphenicol, fosfomycin, macrolides, quinolones, sulfonamides, trimethoprim and tetracyclines. Plasmid replicon types IncHI2 and IncHI2A were detected in all mcr-9-positive isolates.\n\nThe occurrence of mcr-9 was common among clinical ESBL-producing Enterobacteriaceae isolates from horses in Sweden and was linked to the ESBL-encoding gene blaSHV-12 and plasmid replicon types IncHI2 and IncHI2A.", "doi": "10.1016/j.jgar.2019.08.007", "pmid": "31494305", "labels": {"Clinical Genomics Stockholm": "Service", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "S2213-7165(19)30205-X"}], "notes": [], "created": "2020-11-22T14:28:37.132Z", "modified": "2024-01-16T13:48:42.885Z"}, {"entity": "publication", "iuid": "801a1c8a83fa4b0183e5729b84f7a003", "links": {"self": {"href": "https://publications.scilifelab.se/publication/801a1c8a83fa4b0183e5729b84f7a003.json"}, "display": {"href": "https://publications.scilifelab.se/publication/801a1c8a83fa4b0183e5729b84f7a003"}}, "title": "PCSK6 Is a Key Protease in the Control of Smooth Muscle Cell Function in Vascular Remodeling.", "authors": [{"family": "Rykaczewska", "given": "Urszula", "initials": "U"}, {"family": "Suur", "given": "Bianca E", "initials": "BE"}, {"family": "R\u00f6hl", "given": "Samuel", "initials": "S"}, {"family": "Razuvaev", "given": "Anton", "initials": "A"}, {"family": "Lengquist", "given": "Mariette", "initials": "M"}, {"family": "Sabater-Lleal", "given": "Maria", "initials": "M"}, {"family": "van der Laan", "given": "Sander W", "initials": "SW"}, {"family": "Miller", "given": "Clint L", "initials": "CL"}, {"family": "Wirka", "given": "Robert C", "initials": "RC"}, {"family": "Kronqvist", "given": "Malin", "initials": "M"}, {"family": "Gonzalez Diez", "given": "Maria", "initials": "M"}, {"family": "Vesterlund", "given": "Mattias", "initials": "M"}, {"family": "Gillgren", "given": "Peter", "initials": "P"}, {"family": "Odeberg", "given": "Jacob", "initials": "J"}, {"family": "Lindeman", "given": "Jan H", "initials": "JH"}, {"family": "Veglia", "given": "Fabrizio", "initials": "F"}, {"family": "Humphries", "given": "Steve E", "initials": "SE"}, {"family": "de Faire", "given": "Ulf", "initials": "U"}, {"family": "Baldassarre", "given": "Damiano", "initials": "D"}, {"family": "Tremoli", "given": "Elena", "initials": "E"}, {"family": "IMPROVE study group", "given": "", "initials": ""}, {"family": "Lehti\u00f6", "given": "Janne", "initials": "J", "orcid": "0000-0002-8100-9562", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406a97bac744a59b1bc951978994581.json"}}, {"family": "Hansson", "given": "G\u00f6ran K", "initials": "GK"}, {"family": "Paulsson-Berne", "given": "Gabrielle", "initials": "G"}, {"family": "Pasterkamp", "given": "Gerard", "initials": "G"}, {"family": "Quertermous", "given": "Thomas", "initials": "T"}, {"family": "Hamsten", "given": "Anders", "initials": "A"}, {"family": "Eriksson", "given": "Per", "initials": "P"}, {"family": "Hedin", "given": "Ulf", "initials": "U"}, {"family": "Matic", "given": "Ljubica", "initials": "L"}], "type": "journal article", "published": "2020-02-28", "journal": {"volume": "126", "issn": "1524-4571", "issue": "5", "title": "Circ. Res.", "pages": "571-585", "issn-l": "0009-7330"}, "abstract": "PCSKs (Proprotein convertase subtilisins/kexins) are a protease family with unknown functions in vasculature. Previously, we demonstrated PCSK6 upregulation in human atherosclerotic plaques associated with smooth muscle cells (SMCs), inflammation, extracellular matrix remodeling, and mitogens.\n\nHere, we applied a systems biology approach to gain deeper insights into the PCSK6 role in normal and diseased vessel wall.\n\nGenetic analyses revealed association of intronic PCSK6 variant rs1531817 with maximum internal carotid intima-media thickness progression in high-cardiovascular risk subjects. This variant was linked with PCSK6 mRNA expression in healthy aortas and plaques but also with overall plaque SMA+ cell content and pericyte fraction. Increased PCSK6 expression was found in several independent human cohorts comparing atherosclerotic lesions versus healthy arteries, using transcriptomic and proteomic datasets. By immunohistochemistry, PCSK6 was localized to fibrous cap SMA+ cells and neovessels in plaques. In human, rat, and mouse intimal hyperplasia, PCSK6 was expressed by proliferating SMA+ cells and upregulated after 5 days in rat carotid balloon injury model, with positive correlation to PDGFB (platelet-derived growth factor subunit B) and MMP (matrix metalloprotease) 2/MMP14. Here, PCSK6 was shown to colocalize and cointeract with MMP2/MMP14 by in situ proximity ligation assay. Microarrays of carotid arteries from Pcsk6-/- versus control mice revealed suppression of contractile SMC markers, extracellular matrix remodeling enzymes, and cytokines/receptors. Pcsk6-/- mice showed reduced intimal hyperplasia response upon carotid ligation in vivo, accompanied by decreased MMP14 activation and impaired SMC outgrowth from aortic rings ex vivo. PCSK6 silencing in human SMCs in vitro leads to downregulation of contractile markers and increase in MMP2 expression. Conversely, PCSK6 overexpression increased PDGFBB (platelet-derived growth factor BB)-induced cell proliferation and particularly migration.\n\nPCSK6 is a novel protease that induces SMC migration in response to PDGFB, mechanistically via modulation of contractile markers and MMP14 activation. This study establishes PCSK6 as a key regulator of SMC function in vascular remodeling. Visual Overview: An online visual overview is available for this article.", "doi": "10.1161/CIRCRESAHA.119.316063", "pmid": "31893970", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Global Proteomics and Proteogenomics": "Collaborative"}, "xrefs": [], "notes": [], "created": "2020-01-14T10:04:55.756Z", "modified": "2021-11-10T12:53:44.074Z"}, {"entity": "publication", "iuid": "6cb7046ed9eb44dfbf9eb8ac97264bef", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6cb7046ed9eb44dfbf9eb8ac97264bef.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6cb7046ed9eb44dfbf9eb8ac97264bef"}}, "title": "Complete genome and methylome analysis of Neisseria meningitidis associated with increased serogroup Y disease.", "authors": [{"family": "Stenmark", "given": "Bianca", "initials": "B", "orcid": "0000-0003-4637-8626", "researcher": {"href": "https://publications.scilifelab.se/researcher/726c71c7aca148c981b48bde574a2e1c.json"}}, {"family": "Harrison", "given": "Odile B", "initials": "OB"}, {"family": "Eriksson", "given": "Lorraine", "initials": "L"}, {"family": "Anton", "given": "Brian P", "initials": "BP"}, {"family": "Fomenkov", "given": "Alexey", "initials": "A"}, {"family": "Roberts", "given": "Richard J", "initials": "RJ"}, {"family": "Tooming-Klunderud", "given": "Ave", "initials": "A"}, {"family": "Bratcher", "given": "Holly B", "initials": "HB"}, {"family": "Bray", "given": "James E", "initials": "JE"}, {"family": "Thulin-Hedberg", "given": "Sara", "initials": "S"}, {"family": "Maiden", "given": "Martin C J", "initials": "MCJ"}, {"family": "M\u00f6lling", "given": "Paula", "initials": "P"}], "type": "journal article", "published": "2020-02-27", "journal": {"title": "Sci Rep", "issn": "2045-2322", "issn-l": "2045-2322", "volume": "10", "issue": "1", "pages": "3644"}, "abstract": "Invasive meningococcal disease (IMD) due to serogroup Y Neisseria meningitidis emerged in Europe during the 2000s. Draft genomes of serogroup Y isolates in Sweden revealed that although the population structure of these isolates was similar to other serogroup Y isolates internationally, a distinct strain (YI) and more specifically a sublineage (1) of this strain was responsible for the increase of serogroup Y IMD in Sweden. We performed single molecule real-time (SMRT) sequencing on eight serogroup Y isolates from different sublineages to unravel the genetic and epigenetic factors delineating them, in order to understand the serogroup Y emergence. Extensive comparisons between the serogroup Y sublineages of all coding sequences, complex genomic regions, intergenic regions, and methylation motifs revealed small point mutations in genes mainly encoding hypothetical and metabolic proteins, and non-synonymous variants in genes involved in adhesion, iron acquisition, and endotoxin production. The methylation motif CACNNNNNTAC was only found in isolates of sublineage 2. Only seven genes were putatively differentially expressed, and another two genes encoding hypothetical proteins were only present in sublineage 2. These data suggest that the serogroup Y IMD increase in Sweden was most probably due to small changes in genes important for colonization and transmission.", "doi": "10.1038/s41598-020-59509-y", "pmid": "32108139", "labels": {"Clinical Genomics \u00d6rebro": "Technology development", "Clinical Genomics": "Technology development"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-59509-y"}, {"db": "pmc", "key": "PMC7046676"}], "notes": [], "created": "2020-11-27T13:55:39.557Z", "modified": "2021-12-08T12:32:12.168Z"}, {"entity": "publication", "iuid": "f9c089828e5f4a3dac5e5eb778b7f3c2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f9c089828e5f4a3dac5e5eb778b7f3c2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f9c089828e5f4a3dac5e5eb778b7f3c2"}}, "title": "The Relationship Between Polygenic Risk Scores and Cognition in Schizophrenia.", "authors": [{"family": "Richards", "given": "Alexander L", "initials": "AL", "orcid": "0000-0003-3218-7247", "researcher": {"href": "https://publications.scilifelab.se/researcher/d6a0551c61bc4754a742df8b26ef40db.json"}}, {"family": "Pardi\u00f1as", "given": "Antonio F", "initials": "AF"}, {"family": "Frizzati", "given": "Aura", "initials": "A"}, {"family": "Tansey", "given": "Katherine E", "initials": "KE"}, {"family": "Lynham", "given": "Amy J", "initials": "AJ", "orcid": "0000-0002-3189-6888", "researcher": {"href": "https://publications.scilifelab.se/researcher/2c789b2e9aa24bd6ad212dc0a1ddbb96.json"}}, {"family": "Holmans", "given": "Peter", "initials": "P"}, {"family": "Legge", "given": "Sophie E", "initials": "SE"}, {"family": "Savage", "given": "Jeanne E", "initials": "JE"}, {"family": "Agartz", "given": "Ingrid", "initials": "I"}, {"family": "Andreassen", "given": "Ole A", "initials": "OA"}, {"family": "Blokland", "given": "Gabriella A M", "initials": "GAM"}, {"family": "Corvin", "given": "Aiden", "initials": "A"}, {"family": "Cosgrove", "given": "Donna", "initials": "D"}, {"family": "Degenhardt", "given": "Franziska", "initials": "F"}, {"family": "Djurovic", "given": "Srdjan", "initials": "S"}, {"family": "Espeseth", "given": "Thomas", "initials": "T"}, {"family": "Ferraro", "given": "Laura", "initials": "L"}, {"family": "Gayer-Anderson", "given": "Charlotte", "initials": "C"}, {"family": "Giegling", "given": "Ina", "initials": "I"}, {"family": "van Haren", "given": "Neeltje E", "initials": "NE"}, {"family": "Hartmann", "given": "Annette M", "initials": "AM"}, {"family": "Hubert", "given": "John J", "initials": "JJ"}, {"family": "J\u00f6nsson", "given": "Erik G", "initials": "EG"}, {"family": "Konte", "given": "Bettina", "initials": "B"}, {"family": "Lennertz", "given": "Leonhard", "initials": "L"}, {"family": "Olde Loohuis", "given": "Loes M", "initials": "LM"}, {"family": "Melle", "given": "Ingrid", "initials": "I"}, {"family": "Morgan", "given": "Craig", "initials": "C"}, {"family": "Morris", "given": "Derek W", "initials": "DW"}, {"family": "Murray", "given": "Robin M", "initials": "RM"}, {"family": "Nyman", "given": "H\u00e5kan", "initials": "H"}, {"family": "Ophoff", "given": "Roel A", "initials": "RA"}, {"family": "GROUP Investigators", "given": "", "initials": ""}, {"family": "van Os", "given": "Jim", "initials": "J"}, {"family": "EUGEI WP2 Group", "given": "", "initials": ""}, {"family": "Schizophrenia Working Group of the Psychiatric Genomics Consortium", "given": "", "initials": ""}, {"family": "Petryshen", "given": "Tracey L", "initials": "TL"}, {"family": "Quattrone", "given": "Diego", "initials": "D"}, {"family": "Rietschel", "given": "Marcella", "initials": "M"}, {"family": "Rujescu", "given": "Dan", "initials": "D"}, {"family": "Rutten", "given": "Bart P F", "initials": "BPF"}, {"family": "Streit", "given": "Fabian", "initials": "F"}, {"family": "Strohmaier", "given": "Jana", "initials": "J"}, {"family": "Sullivan", "given": "Patrick F", "initials": "PF"}, {"family": "Sundet", "given": "Kjetil", "initials": "K"}, {"family": "Wagner", "given": "Michael", "initials": "M"}, {"family": "Escott-Price", "given": "Valentina", "initials": "V"}, {"family": "Owen", "given": "Michael J", "initials": "MJ"}, {"family": "Donohoe", "given": "Gary", "initials": "G"}, {"family": "O'Donovan", "given": "Michael C", "initials": "MC"}, {"family": "Walters", "given": "James T R", "initials": "JTR"}], "type": "journal article", "published": "2020-02-26", "journal": {"title": "Schizophr Bull", "issn": "1745-1701", "volume": "46", "issue": "2", "pages": "336-344", "issn-l": "0586-7614"}, "abstract": "Cognitive impairment is a clinically important feature of schizophrenia. Polygenic risk score (PRS) methods have demonstrated genetic overlap between schizophrenia, bipolar disorder (BD), major depressive disorder (MDD), educational attainment (EA), and IQ, but very few studies have examined associations between these PRS and cognitive phenotypes within schizophrenia cases.\n\nWe combined genetic and cognitive data in 3034 schizophrenia cases from 11 samples using the general intelligence factor g as the primary measure of cognition. We used linear regression to examine the association between cognition and PRS for EA, IQ, schizophrenia, BD, and MDD. The results were then meta-analyzed across all samples. A genome-wide association studies (GWAS) of cognition was conducted in schizophrenia cases.\n\nPRS for both population IQ (P = 4.39 \u00d7 10-28) and EA (P = 1.27 \u00d7 10-26) were positively correlated with cognition in those with schizophrenia. In contrast, there was no association between cognition in schizophrenia cases and PRS for schizophrenia (P = .39), BD (P = .51), or MDD (P = .49). No individual variant approached genome-wide significance in the GWAS.\n\nCognition in schizophrenia cases is more strongly associated with PRS that index cognitive traits in the general population than PRS for neuropsychiatric disorders. This suggests the mechanisms of cognitive variation within schizophrenia are at least partly independent from those that predispose to schizophrenia diagnosis itself. Our findings indicate that this cognitive variation arises at least in part due to genetic factors shared with cognitive performance in populations and is not solely due to illness or treatment-related factors, although our findings are consistent with important contributions from these factors.", "doi": "10.1093/schbul/sbz061", "pmid": "31206164", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "5519548"}, {"db": "pmc", "key": "PMC7442352"}], "notes": [], "created": "2020-02-27T09:21:00.659Z", "modified": "2021-11-10T12:53:46.726Z"}, {"entity": "publication", "iuid": "e411a47644c249b1baa88bbcf29a2aa2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e411a47644c249b1baa88bbcf29a2aa2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e411a47644c249b1baa88bbcf29a2aa2"}}, "title": "Streptococcus pneumoniae Nasopharyngeal Carriage among PCV-10-Vaccinated HIV-1-Infected Children with Maintained Serological Memory in Ethiopia.", "authors": [{"family": "Lemma", "given": "Mahlet", "initials": "M"}, {"family": "Bekele", "given": "Yonas", "initials": "Y"}, {"family": "Petkov", "given": "Stefan", "initials": "S"}, {"family": "H\u00e4gglund", "given": "Moa", "initials": "M"}, {"family": "Petros", "given": "Beyene", "initials": "B"}, {"family": "Aseffa", "given": "Abraham", "initials": "A", "orcid": "0000-0002-8028-1150", "researcher": {"href": "https://publications.scilifelab.se/researcher/5e29e98d0dc043b38f4d43bafa92d580.json"}}, {"family": "Howe", "given": "Rawleigh", "initials": "R"}, {"family": "Chiodi", "given": "Francesca", "initials": "F"}], "type": "journal article", "published": "2020-02-25", "journal": {"title": "Pathogens", "issn": "2076-0817", "issn-l": null, "volume": "9", "issue": "3", "pages": "159"}, "abstract": "Streptococcus pneumoniae (S. pneumoniae) vaccines have substantially reduced the burden of invasive pneumococcal diseases (IPDs) worldwide. Despite high coverage with S. pneumoniae vaccination, upper-respiratory-tract colonization by S. pneumoniae is still common. We assessed maintenance of serological responses to S. pneumoniae serotypes included in PCV-10 by ELISA in HIV-1-infected children (n = 50) and age-matched controls (n = 50) in Ethiopia. We isolated S. pneumoniae in nasopharyngeal swabs and determined S. pneumoniae serotype by whole genome sequencing (WGS). Comparable levels of S. pneumoniae serotype-specific IgG concentrations were detected in plasma of HIV-1-infected children and matched controls, with geometric mean concentrations (GMCs) consistently higher than the protective threshold for PCV-10 serotypes of 0.35 \u03bcg/mL. We isolated S. pneumoniae from 38 (out of 97) nasopharyngeal swabs, 25 from HIV-1-infected children and 13 from controls. WGS based serotyping revealed 22 known S. pneumoniae serotypes and 2 nontypeable (NT) isolates. Non-PCV-10 serotypes represented >90% of isolates. We showed that HIV-1-infected children and matched controls in Ethiopia carry a level of maintained serological memory to PCV-10 considered protective for IPDs. We identified a higher proportion of nasopharyngeal carriage with highly pathogenic S. pneumoniae non-PCV strains among HIV-1-infected children compared to controls.", "doi": "10.3390/pathogens9030159", "pmid": "32106620", "labels": {"Clinical Genomics Stockholm": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "pathogens9030159"}, {"db": "pmc", "key": "PMC7157605"}], "notes": [], "created": "2020-12-03T09:15:57.782Z", "modified": "2023-05-22T11:24:04.348Z"}, {"entity": "publication", "iuid": "22a173ef02f045c28253c98404dcdc0a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/22a173ef02f045c28253c98404dcdc0a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/22a173ef02f045c28253c98404dcdc0a"}}, "title": "Patterns of African and Asian admixture in the Afrikaner population of South Africa.", "authors": [{"family": "Hollfelder", "given": "N", "initials": "N"}, {"family": "Erasmus", "given": "J C", "initials": "JC"}, {"family": "Hammaren", "given": "R", "initials": "R"}, {"family": "Vicente", "given": "M", "initials": "M"}, {"family": "Jakobsson", "given": "M", "initials": "M", "orcid": "0000-0001-7840-7853", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a4abe0fcb20492d9ec849c9fbf58a71.json"}}, {"family": "Greeff", "given": "J M", "initials": "JM"}, {"family": "Schlebusch", "given": "C M", "initials": "CM", "orcid": "0000-0002-8160-9621", "researcher": {"href": "https://publications.scilifelab.se/researcher/682f10853c1145649b8c76680605dd9b.json"}}], "type": "journal article", "published": "2020-02-24", "journal": {"title": "BMC Biol.", "issn": "1741-7007", "volume": "18", "issue": "1", "pages": "16", "issn-l": "1741-7007"}, "abstract": "The Afrikaner population of South Africa is the descendants of European colonists who started to colonize the Cape of Good Hope in the 1600s. In the early days of the colony, mixed unions between European males and non-European females gave rise to admixed children who later became incorporated into either the Afrikaner or the Coloured populations of South Africa. Differences in ancestry, social class, culture, sex ratio and geographic structure led to distinct and characteristic admixture patterns in the Afrikaner and Coloured populations. The Afrikaner population has a predominant European composition, whereas the Coloured population has more diverse ancestries. Genealogical records previously estimated the contribution of non-Europeans into the Afrikaners to be between 5.5 and 7.2%.\n\nTo investigate the genetic ancestry of the Afrikaner population today (11-13 generations after initial colonization), we genotyped approximately five million genome-wide markers in 77 Afrikaner individuals and compared their genotypes to populations across the world to determine parental source populations and admixture proportions. We found that the majority of Afrikaner ancestry (average 95.3%) came from European populations (specifically northwestern European populations), but that almost all Afrikaners had admixture from non-Europeans. The non-European admixture originated mostly from people who were brought to South Africa as slaves and, to a lesser extent, from local Khoe-San groups. Furthermore, despite a potentially small founding population, there is no sign of a recent bottleneck in the Afrikaner compared to other European populations. Admixture amongst diverse groups from Europe and elsewhere during early colonial times might have counterbalanced the effects of a small founding population.\n\nWhile Afrikaners have an ancestry predominantly from northwestern Europe, non-European admixture signals are ubiquitous in the Afrikaner population. Interesting patterns and similarities could be observed between genealogical predictions and our genetic inferences. Afrikaners today have comparable inbreeding levels to current-day European populations.", "doi": "10.1186/s12915-020-0746-1", "pmid": "32089133", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12915-020-0746-1"}, {"db": "pmc", "key": "PMC7038537"}], "notes": [], "created": "2020-02-28T12:44:13.878Z", "modified": "2024-01-16T13:48:42.894Z"}, {"entity": "publication", "iuid": "334f24d1e0724ca99b3736c82f798484", "links": {"self": {"href": "https://publications.scilifelab.se/publication/334f24d1e0724ca99b3736c82f798484.json"}, "display": {"href": "https://publications.scilifelab.se/publication/334f24d1e0724ca99b3736c82f798484"}}, "title": "rs953413 Regulates Polyunsaturated Fatty Acid Metabolism by Modulating ELOVL2 Expression.", "authors": [{"family": "Pan", "given": "Gang", "initials": "G"}, {"family": "Cavalli", "given": "Marco", "initials": "M"}, {"family": "Carlsson", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Skrtic", "given": "Stanko", "initials": "S"}, {"family": "Kumar", "given": "Chanchal", "initials": "C"}, {"family": "Wadelius", "given": "Claes", "initials": "C", "orcid": "0000-0002-2033-7829", "researcher": {"href": "https://publications.scilifelab.se/researcher/2ec5ca1122024da4893b61e329a5ece5.json"}}], "type": "journal article", "published": "2020-02-21", "journal": {"title": "iScience", "issn": "2589-0042", "volume": "23", "issue": "2", "pages": "100808", "issn-l": "2589-0042"}, "abstract": "Long-chain polyunsaturated fatty acids (LC-PUFAs) influence human health in several areas, including cardiovascular disease, diabetes, fatty liver disease, and cancer. ELOVL2 encodes one of the key enzymes in the in vivo synthesis of LC-PUFAs from their precursors. Variants near ELOVL2 have repeatedly been associated with levels of LC-PUFA-derived metabolites in genome-wide association studies (GWAS), but the mechanisms behind these observations remain poorly defined. In this study, we found that rs953413, located in the first intron of ELOVL2, lies within a functional FOXA and HNF4\u03b1 cooperative binding site. The G allele of rs953413 increases binding of FOXA1/FOXA2 and HNF4\u03b1 to an evolutionarily conserved enhancer element, conferring allele-specific upregulation of the rs953413-associated gene ELOVL2. The expression of ELOVL2 was significantly downregulated by both FOXA1 and HNF4\u03b1 knockdown and CRISPR/Cas9-mediated direct mutation to the enhancer element. Our results suggest that rs953413 regulates LC-PUFAs metabolism by altering ELOVL2 expression through FOXA1/FOXA2 and HNF4\u03b1 cooperation.", "doi": "10.1016/j.isci.2019.100808", "pmid": "31928966", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S2589-0042(19)30554-1"}, {"db": "pmc", "key": "PMC7033636"}], "notes": [], "created": "2020-11-16T09:09:06.978Z", "modified": "2024-01-16T13:48:42.901Z"}, {"entity": "publication", "iuid": "9f85daf2c35c4935a50ff9ddf7732c78", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9f85daf2c35c4935a50ff9ddf7732c78.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9f85daf2c35c4935a50ff9ddf7732c78"}}, "title": "In Vitro Regeneration of Decellularized Pig Esophagus Using Human Amniotic Stem Cells.", "authors": [{"family": "Nayakawde", "given": "Nikhil B", "initials": "NB"}, {"family": "Methe", "given": "Ketaki", "initials": "K"}, {"family": "Banerjee", "given": "Debashish", "initials": "D"}, {"family": "Berg", "given": "Malin", "initials": "M"}, {"family": "Premaratne", "given": "Goditha U", "initials": "GU"}, {"family": "Olausson", "given": "Michael", "initials": "M"}], "type": "journal article", "published": "2020-02-21", "journal": {"title": "Biores Open Access", "issn": "2164-7844", "volume": "9", "issue": "1", "pages": "22-36", "issn-l": null}, "abstract": "Decellularization of esophagus was studied using three different protocols. The sodium deoxycholate/DNase-I (SDC/DNase-I) method was the most successful as evidenced by histology and DNA quantification of the acellular scaffolds. Acellular scaffolds were further analyzed and compared with native tissue by histology, quantitative analysis of DNA, and extracellular matrix (ECM) proteins. Histologically, the SDC/DNase-I protocol effectively produced scaffold with preserved structural architecture similar to native tissue architecture devoid of any cell nucleus. ECM proteins, such as collagen, elastin, and glycosaminoglycans were present even after detergent-enzymatic decellularization. Immunohistochemical analysis of acellular scaffold showed weak expression of Gal 1, 3 Gal epitope compared with native tissue. For performing recellularization, human amnion-derived mesenchymal stem cells (MSCs) and epithelial cells were seeded onto acellular esophagus in a perfusion-rotation bioreactor. In recellularized esophagus, immunohistochemistry showed infiltration of MSCs from adventitia into the muscularis externa and differentiation of MSCs into the smooth muscle actin and few endothelial cells (CD31). Our study demonstrates successful preparation and characterization of a decellularized esophagus with reduced load of Gal 1, 3 Gal epitope with preserved architecture and ECM proteins similar to native tissue. Upon subsequent recellularization, xenogeneic acellular esophagus also supported stem cell growth and partial differentiation of stem cells. Hence, the current study offers the hope for preparing a tissue-engineered esophagus in vitro which can be transplanted further into pigs for further in vivo evaluation.", "doi": "10.1089/biores.2019.0054", "pmid": "32117597", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7047253"}, {"db": "pii", "key": "10.1089/biores.2019.0054"}], "notes": [], "created": "2023-02-16T08:08:30.830Z", "modified": "2023-02-16T08:08:30.859Z"}, {"entity": "publication", "iuid": "5d45e246a4a448159af62be64061ffaa", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5d45e246a4a448159af62be64061ffaa.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5d45e246a4a448159af62be64061ffaa"}}, "title": "Dominance of Mating Type A1 and Indication of Epigenetic Effects During Early Stages of Mating in Phytophthora infestans.", "authors": [{"family": "Tzelepis", "given": "Georgios", "initials": "G"}, {"family": "Hod\u00e9n", "given": "Kristian Persson", "initials": "KP"}, {"family": "Fogelqvist", "given": "Johan", "initials": "J"}, {"family": "\u00c5sman", "given": "Anna K M", "initials": "AKM"}, {"family": "Vetukuri", "given": "Ramesh R", "initials": "RR"}, {"family": "Dixelius", "given": "Christina", "initials": "C"}], "type": "journal article", "published": "2020-02-21", "journal": {"title": "Front Microbiol", "issn": "1664-302X", "volume": "11", "issue": null, "pages": "252", "issn-l": "1664-302X"}, "abstract": "The potato late blight pathogen Phytophthora infestans has both an asexual and a sexual mode of reproduction. In Scandinavia, the pathogen is reproducing sexually on a regular basis, whereas clonal lineages dominate in other geographical regions. This study aimed at elucidating events or key genes underlying this difference in sexual behavior. First, the transcriptomes of eight strains, known as either clonal or sexual, were compared during early stages of mating. Principal component analysis (PCA) divided the samples in two clusters A and B and a clear grouping of the mating samples together with the A1 mating type parents was observed. Induction of genes encoding DNA adenine N6-methylation (6mA) methyl-transferases clearly showed a bias toward the cluster A. In contrast, the Avrblb2 effector gene family was highly induced in most of the mating samples and was associated with cluster B in the PCA, similarly to genes coding for acetyl-transferases, which play an important role in RXLR modification prior to secretion. Avrblb2 knock-down strains displayed a reduction in virulence and oospore formation, suggesting a role during the mating process. In conclusion, a number of gene candidates important for the reproductive processes were revealed. The results suggest a possible epigenetic influence and involvement of specific RXLR effectors in mating-related processes.", "doi": "10.3389/fmicb.2020.00252", "pmid": "32153537", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7046690"}], "notes": [], "created": "2020-07-08T13:04:13.663Z", "modified": "2021-11-10T12:53:51.325Z"}, {"entity": "publication", "iuid": "35806cca1dd04fef9c3505fa53346c1e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/35806cca1dd04fef9c3505fa53346c1e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/35806cca1dd04fef9c3505fa53346c1e"}}, "title": "Biomolecular analyses reveal the age, sex and species identity of a near-intact Pleistocene bird carcass.", "authors": [{"family": "Dussex", "given": "Nicolas", "initials": "N", "orcid": "0000-0002-9179-8593", "researcher": {"href": "https://publications.scilifelab.se/researcher/a8ce91163131424a99f8815c2cb96953.json"}}, {"family": "Stanton", "given": "David W G", "initials": "DWG"}, {"family": "Sigeman", "given": "Hanna", "initials": "H", "orcid": "0000-0002-1457-4174", "researcher": {"href": "https://publications.scilifelab.se/researcher/f75fea472d1d495a92228c50bd63891e.json"}}, {"family": "Ericson", "given": "Per G P", "initials": "PGP"}, {"family": "Gill", "given": "Jacquelyn", "initials": "J"}, {"family": "Fisher", "given": "Daniel C", "initials": "DC"}, {"family": "Protopopov", "given": "Albert V", "initials": "AV"}, {"family": "Herridge", "given": "Victoria L", "initials": "VL"}, {"family": "Plotnikov", "given": "Valery", "initials": "V", "orcid": "0000-0002-4870-3499", "researcher": {"href": "https://publications.scilifelab.se/researcher/378b10136be74923bff019375f5d6c91.json"}}, {"family": "Hansson", "given": "Bengt", "initials": "B", "orcid": "0000-0001-6694-8169", "researcher": {"href": "https://publications.scilifelab.se/researcher/01f0144e207c41dcbc4d5aec68690e4b.json"}}, {"family": "Dal\u00e9n", "given": "Love", "initials": "L", "orcid": "0000-0001-8270-7613", "researcher": {"href": "https://publications.scilifelab.se/researcher/48ecf726779249ac9d12f4f7a1cc62bf.json"}}], "type": "historical article", "published": "2020-02-21", "journal": {"title": "Commun Biol", "issn": "2399-3642", "volume": "3", "issue": "1", "pages": "84", "issn-l": "2399-3642"}, "abstract": "Ancient remains found in permafrost represent a rare opportunity to study past ecosystems. Here, we present an exceptionally well-preserved ancient bird carcass found in the Siberian permafrost, along with a radiocarbon date and a reconstruction of its complete mitochondrial genome. The carcass was radiocarbon dated to approximately 44-49 ka BP, and was genetically identified as a female horned lark. This is a species that usually inhabits open habitat, such as the steppe environment that existed in Siberia at the time. This near-intact carcass highlights the potential of permafrost remains for evolutionary studies that combine both morphology and ancient nucleic acids.", "doi": "10.1038/s42003-020-0806-7", "pmid": "32081985", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s42003-020-0806-7"}, {"db": "pmc", "key": "PMC7035339"}], "notes": [], "created": "2020-07-08T13:04:57.570Z", "modified": "2024-01-16T13:48:42.909Z"}, {"entity": "publication", "iuid": "20058bace075434c983d36591e52eab6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/20058bace075434c983d36591e52eab6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/20058bace075434c983d36591e52eab6"}}, "title": "Backbone Cyclization and Dimerization of LL-37-Derived Peptides Enhance Antimicrobial Activity and Proteolytic Stability.", "authors": [{"family": "Gunasekera", "given": "Sunithi", "initials": "S"}, {"family": "Muhammad", "given": "Taj", "initials": "T"}, {"family": "Str\u00f6mstedt", "given": "Adam A", "initials": "AA"}, {"family": "Rosengren", "given": "K Johan", "initials": "KJ"}, {"family": "G\u00f6ransson", "given": "Ulf", "initials": "U"}], "type": "journal article", "published": "2020-02-21", "journal": {"title": "Front Microbiol", "issn": "1664-302X", "volume": "11", "issue": null, "pages": "168", "issn-l": "1664-302X"}, "abstract": "Can antimicrobial activity and peptide stability of alpha-helical peptides be increased by making them into dimers and macrocycles? Here, we explore that concept by using KR-12 as the starting point for peptide engineering. KR-12 has previously been determined as the minimalized antimicrobial fragment of the human host defense peptide LL-37. Backbone-cyclized KR-12 dimers, tethered by linkers of two to four amino acid residues, were synthesized and their antimicrobial activity, proteolytic stability and structures characterized. A modified KR-12 sequence, with substitutions at previously identified key residues, were also included in the screening panel. The backbone cyclized KR-12 dimers showed improved antimicrobial activity and increased stability compared to monomeric KR-12. The most active cyclic dimer displayed 16-fold higher antibacterial activity compared to KR-12 against Pseudomonas aeruginosa and Staphylococcus aureus, and 8-fold increased fungicidal activity against Candida albicans. It also showed increased hemolytic and cytotoxic activity. Enhanced antimicrobial activity coincided with increased membrane permeabilization of liposomes with one distinct discrepancy: monomeric KR-12 was much less disruptive of liposomes with bacterial lipid composition compared to liposomes from fungal lipid extract. Circular dichroism showed that the four-residue linked most active cyclic dimer had 65% helical content when bound to lyso-phosphatidylglycerol micelles, indicating that the helical propensity of the parent peptide is maintained in the new macrocyclic form. In conclusion, the current work on KR-12 suggests that dimerization together with backbone cyclization is an effective strategy for improving both potency and stability of linear antimicrobial peptides.", "doi": "10.3389/fmicb.2020.00168", "pmid": "32153522", "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7046553"}], "notes": [], "created": "2020-12-11T09:12:47.582Z", "modified": "2025-10-17T13:03:57.093Z"}, {"entity": "publication", "iuid": "bf7795e36d7a4d05a6a8da88797ee3ff", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bf7795e36d7a4d05a6a8da88797ee3ff.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bf7795e36d7a4d05a6a8da88797ee3ff"}}, "title": "Subtle structural alterations in G-quadruplex DNA regulate site specificity of fluorescence light-up probes.", "authors": [{"family": "Kumar", "given": "Rajendra", "initials": "R", "orcid": "0000-0002-7268-9519", "researcher": {"href": "https://publications.scilifelab.se/researcher/4ba57d44c650444aa51a030541d3bba7.json"}}, {"family": "Chand", "given": "Karam", "initials": "K"}, {"family": "Bhowmik", "given": "Sudipta", "initials": "S"}, {"family": "Das", "given": "Rabindra Nath", "initials": "RN"}, {"family": "Bhattacharjee", "given": "Snehasish", "initials": "S"}, {"family": "Hedenstr\u00f6m", "given": "Mattias", "initials": "M"}, {"family": "Chorell", "given": "Erik", "initials": "E", "orcid": "0000-0003-2523-1940", "researcher": {"href": "https://publications.scilifelab.se/researcher/ada783ae0a824621a3b8e1024aae13a4.json"}}], "type": "journal article", "published": "2020-02-20", "journal": {"title": "Nucleic Acids Res.", "issn": "1362-4962", "volume": "48", "issue": "3", "pages": "1108-1119", "issn-l": "0305-1048"}, "abstract": "G-quadruplex (G4) DNA structures are linked to key biological processes and human diseases. Small molecules that target specific G4 DNA structures and signal their presence would therefore be of great value as chemical research tools with potential to further advance towards diagnostic and therapeutic developments. However, the development of these types of specific compounds remain as a great challenge. In here, we have developed a compound with ability to specifically signal a certain c-MYC G4 DNA structure through a fluorescence light-up mechanism. Despite the compound's two binding sites on the G4 DNA structure, only one of them result in the fluorescence light-up effect. This G-tetrad selectivity proved to originate from a difference in flexibility that affected the binding affinity and tilt the compound out of the planar conformation required for the fluorescence light-up mechanism. The intertwined relation between the presented factors is likely the reason for the lack of examples using rational design to develop compounds with turn-on emission that specifically target certain G4 DNA structures. However, this study shows that it is indeed possible to develop such compounds and present insights into the molecular details of specific G4 DNA recognition and signaling to advance future studies of G4 biology.", "doi": "10.1093/nar/gkz1205", "pmid": "31912160", "labels": {"Swedish NMR Centre": "Collaborative"}, "xrefs": [{"db": "pii", "key": "5698139"}, {"db": "pmc", "key": "PMC7026600"}], "notes": [], "created": "2020-03-30T11:32:27.521Z", "modified": "2025-10-17T13:03:57.104Z"}, {"entity": "publication", "iuid": "9909cb432f9745cbafcae0c1b08b44fd", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9909cb432f9745cbafcae0c1b08b44fd.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9909cb432f9745cbafcae0c1b08b44fd"}}, "title": "Primary cell wall inspired micro containers as a step towards a synthetic plant cell.", "authors": [{"family": "Paulraj", "given": "T", "initials": "T", "orcid": "0000-0001-5098-3525", "researcher": {"href": "https://publications.scilifelab.se/researcher/9be07d632ea8443fa8bfa2aaee6c93af.json"}}, {"family": "Wennmalm", "given": "S", "initials": "S"}, {"family": "Wieland", "given": "D C F", "initials": "DCF"}, {"family": "Riazanova", "given": "A V", "initials": "AV"}, {"family": "D\u0117dinait\u0117", "given": "A", "initials": "A"}, {"family": "G\u00fcnther Pomorski", "given": "T", "initials": "T"}, {"family": "C\u00e1rdenas", "given": "M", "initials": "M"}, {"family": "Svagan", "given": "A J", "initials": "AJ"}], "type": "journal article", "published": "2020-02-19", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "11", "issue": "1", "pages": "958", "issn-l": "2041-1723"}, "abstract": "The structural integrity of living plant cells heavily relies on the plant cell wall containing a nanofibrous cellulose skeleton. Hence, if synthetic plant cells consist of such a cell wall, they would allow for manipulation into more complex synthetic plant structures. Herein, we have overcome the fundamental difficulties associated with assembling lipid vesicles with cellulosic nanofibers (CNFs). We prepare plantosomes with an outer shell of CNF and pectin, and beneath this, a thin layer of lipids (oleic acid and phospholipids) that surrounds a water core. By exploiting the phase behavior of the lipids, regulated by pH and Mg2+ ions, we form vesicle-crowded interiors that change the outer dimension of the plantosomes, mimicking the expansion in real plant cells during, e.g., growth. The internal pressure enables growth of lipid tubules through the plantosome cell wall, which paves the way to the development of hierarchical plant structures and advanced synthetic plant cell mimics.", "doi": "10.1038/s41467-020-14718-x", "pmid": "32075974", "labels": {"Integrated Microscopy Technologies Stockholm": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-020-14718-x"}, {"db": "pmc", "key": "PMC7031234"}], "notes": [], "created": "2020-06-29T15:46:04.008Z", "modified": "2021-11-10T12:53:55.840Z"}, {"entity": "publication", "iuid": "51f1cee219854f9f9ec98b890e43ad35", "links": {"self": {"href": "https://publications.scilifelab.se/publication/51f1cee219854f9f9ec98b890e43ad35.json"}, "display": {"href": "https://publications.scilifelab.se/publication/51f1cee219854f9f9ec98b890e43ad35"}}, "title": "Validation of Novel Prognostic Biomarkers for Early-Stage Clear-Cell, Endometrioid and Mucinous Ovarian Carcinomas Using Immunohistochemistry.", "authors": [{"family": "Engqvist", "given": "Hanna", "initials": "H"}, {"family": "Parris", "given": "Toshima Z", "initials": "TZ"}, {"family": "Kov\u00e1cs", "given": "Anik\u00f3", "initials": "A"}, {"family": "R\u00f6nnerman", "given": "Elisabeth Werner", "initials": "EW"}, {"family": "Sundfeldt", "given": "Karin", "initials": "K"}, {"family": "Karlsson", "given": "Per", "initials": "P"}, {"family": "Helou", "given": "Khalil", "initials": "K"}], "type": "journal article", "published": "2020-02-18", "journal": {"title": "Front Oncol", "issn": "2234-943X", "volume": "10", "issue": null, "pages": "162", "issn-l": "2234-943X"}, "abstract": "Early-stage (I and II) ovarian carcinoma patients generally have good prognosis. Yet, some patients die earlier than expected. Thus, it is important to stratify early-stage patients into risk groups to identify those in need of more aggressive treatment regimens. The prognostic value of 29 histotype-specific biomarkers identified using RNA sequencing was evaluated for early-stage clear-cell (CCC), endometrioid (EC) and mucinous (MC) ovarian carcinomas (n = 112) using immunohistochemistry on tissue microarrays. Biomarkers with prognostic significance were further evaluated in an external ovarian carcinoma data set using the web-based Kaplan-Meier plotter tool. Here, we provide evidence of aberrant protein expression patterns and prognostic significance of 17 novel histotype-specific prognostic biomarkers [10 for CCC (ARPC2, CCT5, GNB1, KCTD10, NUP155, RPL13A, RPL37, SETD3, SMYD2, TRIO), three for EC (CECR1, KIF26B, PIK3CA), and four for MC (CHEK1, FOXM1, KIF23, PARPBP)], suggesting biological heterogeneity within the histotypes. Combined predictive models comprising the protein expression status of the validated CCC, EC and MC biomarkers together with established clinical markers (age, stage, CA125, ploidy) improved the predictive power in comparison with models containing established clinical markers alone, further strengthening the importance of the biomarkers in ovarian carcinoma. Further, even improved predictive powers were demonstrated when combining these models with our previously identified prognostic biomarkers PITHD1 (CCC) and GPR158 (MC). Moreover, the proteins demonstrated improved risk prediction of CCC-, EC-, and MC-associated ovarian carcinoma survival. The novel histotype-specific prognostic biomarkers may not only improve prognostication and patient stratification of early-stage ovarian carcinomas, but may also guide future clinical therapy decisions.", "doi": "10.3389/fonc.2020.00162", "pmid": "32133296", "labels": {"NGI Stockholm (Genomics Applications)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7040170"}], "notes": [], "created": "2021-01-08T16:29:14.665Z", "modified": "2024-01-16T13:48:42.923Z"}, {"entity": "publication", "iuid": "0c127496a7284fb2bb6e56ab56e88382", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0c127496a7284fb2bb6e56ab56e88382.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0c127496a7284fb2bb6e56ab56e88382"}}, "title": "Managed and Unmanaged Pinus sylvestris Forest Stands Harbour Similar Diversity and Composition of the Phyllosphere and Soil Fungi.", "authors": [{"family": "Lynikien\u0117", "given": "J\u016brat\u0117", "initials": "J"}, {"family": "Mar\u010diulynien\u0117", "given": "Diana", "initials": "D", "orcid": "0000-0002-0501-6680", "researcher": {"href": "https://publications.scilifelab.se/researcher/c8b0d5aa3ca542d2a170f4becba05f43.json"}}, {"family": "Mar\u010diulynas", "given": "Adas", "initials": "A"}, {"family": "Gedminas", "given": "Art\u016bras", "initials": "A"}, {"family": "Vai\u010diukyn\u0117", "given": "Migl\u0117", "initials": "M"}, {"family": "Menkis", "given": "Audrius", "initials": "A", "orcid": "0000-0002-6545-8907", "researcher": {"href": "https://publications.scilifelab.se/researcher/7d4d16d281344b9f9cf2c3c27fb40f06.json"}}], "type": "journal article", "published": "2020-02-15", "journal": {"title": "Microorganisms", "issn": "2076-2607", "volume": "8", "issue": "2", "pages": "259", "issn-l": "2076-2607"}, "abstract": "The aim was to assess fungal communities associated with living needles and soil of Pinus sylvestris in managed and unmanaged forest stands to get a better understanding of whether and how different intensities of forest management affects fungal diversity and community composition under the north temperate forest zone conditions. The study was carried out in three national parks in Lithuania. Each included five study sites in managed stands and five in unmanaged stands. At each site, three random soil cores and five random last-year needle samples were collected. Following DNA isolation, a DNA fragment of the ITS2 rRNA gene region of each sample was individually amplified and subjected to high-throughput sequencing. Analysis of 195,808 high-quality reads showed the presence of 1909 fungal taxa. Richness and composition of fungal taxa were similar in each substrate (needles and soil) in managed vs. unmanaged sites. The most common fungi in needles were Coleosporium campanulae (12.4% of all fungal sequences), Unidentified sp. 3980_1 (12.4%), Unidentified sp. 3980_4 (4.1%) and Sydowia polyspora (3.1%). In soil: Unidentified sp. 3980_21 (8.6%), Umbelopsis nana (8.2%), Archaeorhizomyces sp. 3980_5 (8.1%) and Penicillium spinulosum (6.3%). The results demonstrated that managed and unmanaged P. sylvestris stands support similar diversity and composition of fungal communities associated with living needles and soil.", "doi": "10.3390/microorganisms8020259", "pmid": "32075257", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service"}, "xrefs": [{"db": "pii", "key": "microorganisms8020259"}, {"db": "pmc", "key": "PMC7074758"}], "notes": [], "created": "2020-03-19T09:25:02.693Z", "modified": "2021-11-10T12:53:59.477Z"}, {"entity": "publication", "iuid": "26d44760a5c0418f99720459af86f069", "links": {"self": {"href": "https://publications.scilifelab.se/publication/26d44760a5c0418f99720459af86f069.json"}, "display": {"href": "https://publications.scilifelab.se/publication/26d44760a5c0418f99720459af86f069"}}, "title": "The First Structure of an Active Mammalian dCTPase and its Complexes With Substrate Analogs and Products.", "authors": [{"family": "Scaletti", "given": "Emma", "initials": "E"}, {"family": "Claesson", "given": "Magnus", "initials": "M"}, {"family": "Helleday", "given": "Thomas", "initials": "T", "orcid": "0000-0002-7384-092X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d7256c271ea4adea404d4ff355f804e.json"}}, {"family": "Jemth", "given": "Ann-Sofie", "initials": "AS"}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P"}], "type": "journal article", "published": "2020-02-14", "journal": {"title": "J. Mol. Biol.", "issn": "1089-8638", "volume": "432", "issue": "4", "pages": "1126-1142", "issn-l": "0022-2836"}, "abstract": "Precise regulation of dNTPs within the cellular nucleotide pool is essential for high accuracy of DNA replication and is critical for retaining the genomic integrity. Recently, human dCTPase (deoxycytidine triphosphatase), also known as DCTPP1 (human all-alpha dCTP pyrophosphatase 1), has been revealed to be a key player in the balance of pyrimidine nucleotide concentrations within cells, with DCTPP1 deficiency causing DNA damage and genetic instability in both chromosomal and mitochondrial DNA. DCTPP1 also exhibits an additional \"house cleaning\" function as it has been shown to be highly active against modified cytidine triphosphates, such as 5-methyl-dCTP, which, if incorrectly incorporated into DNA can introduce undesirable epigenetic marking. To date, structural studies of mammalian dCTPase have been limited to inactive constructs, which do not provide information regarding the catalytic mechanism of this important enzyme. We present here the first structures of an active mammalian dCTPase from M. musculus in complex with the nonhydrolyzable substrate analog dCMPNPP and the products 5-Me-dCMP and dCMP. These structures provide clear insights into substrate binding and catalysis and clearly elucidate why previous structures of mammalian dCTPase were catalytically inactive. The overall structure of M. musculus dCTPase is highly similar to enzymes from the all-alpha NTP phosphohydrolase superfamily. Comparison of M. musculus dCTPase with homologs from a diverse range of mammals, including humans, shows that the residues, which contribute to substrate recognition, are entirely conserved, further supporting the importance of this enzyme in the protection of genomic integrity in mammalian cells.", "doi": "10.1016/j.jmb.2020.01.005", "pmid": "31954130", "labels": {"Protein Science Facility (PSF)": "Service"}, "xrefs": [{"db": "pii", "key": "S0022-2836(20)30024-3"}], "notes": [], "created": "2020-03-22T10:15:17.482Z", "modified": "2021-11-10T12:54:00.548Z"}, {"entity": "publication", "iuid": "c1de8d695c1944ae8db24b9a04b4ab8a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c1de8d695c1944ae8db24b9a04b4ab8a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c1de8d695c1944ae8db24b9a04b4ab8a"}}, "title": "Refined detection and phasing of structural aberrations in pediatric acute lymphoblastic leukemia by linked-read whole-genome sequencing.", "authors": [{"family": "Nordlund", "given": "Jessica", "initials": "J", "orcid": "0000-0001-8699-9959", "researcher": {"href": "https://publications.scilifelab.se/researcher/ddf48c9262134821bcc6ce1180049753.json"}}, {"family": "Marincevic-Zuniga", "given": "Yanara", "initials": "Y"}, {"family": "Cavelier", "given": "Lucia", "initials": "L", "orcid": "0009-0003-8195-370X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f01226edb140436da0c9d166c1f5fe51.json"}}, {"family": "Raine", "given": "Amanda", "initials": "A"}, {"family": "Martin", "given": "Tom", "initials": "T"}, {"family": "Lundmark", "given": "Anders", "initials": "A"}, {"family": "Abrahamsson", "given": "Jonas", "initials": "J"}, {"family": "Nor\u00e9n-Nystr\u00f6m", "given": "Ulrika", "initials": "U"}, {"family": "L\u00f6nnerholm", "given": "Gudmar", "initials": "G"}, {"family": "Syv\u00e4nen", "given": "Ann-Christine", "initials": "AC", "orcid": "0000-0002-9681-9146", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7012e35025543379380cb90efd71243.json"}}], "type": "journal article", "published": "2020-02-13", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "2512", "issn-l": "2045-2322"}, "abstract": "Structural chromosomal rearrangements that can lead to in-frame gene-fusions are a leading source of information for diagnosis, risk stratification, and prognosis in pediatric acute lymphoblastic leukemia (ALL). Traditional methods such as karyotyping and FISH struggle to accurately identify and phase such large-scale chromosomal aberrations in ALL genomes. We therefore evaluated linked-read WGS for detecting chromosomal rearrangements in primary samples of from 12 patients diagnosed with ALL. We assessed the effect of input DNA quality on phased haplotype block size and the detectability of copy number aberrations and structural variants in the ALL genomes. We found that biobanked DNA isolated by standard column-based extraction methods was sufficient to detect chromosomal rearrangements even at low 10x sequencing coverage. Linked-read WGS enabled precise, allele-specific, digital karyotyping at a base-pair resolution for a wide range of structural variants including complex rearrangements and aneuploidy assessment. With use of haplotype information from the linked-reads, we also identified previously unknown structural variants, such as a compound heterozygous deletion of ERG in a patient with the DUX4-IGH fusion gene. We conclude that linked-read WGS allows detection of important pathogenic variants in ALL genomes at a resolution beyond that of traditional karyotyping and FISH.", "doi": "10.1038/s41598-020-59214-w", "pmid": "32054878", "labels": {"National Genomics Infrastructure": "Collaborative", "NGI Uppsala (SNP&SEQ Technology Platform)": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-59214-w"}, {"db": "pmc", "key": "PMC7018692"}], "notes": [], "created": "2020-11-05T12:22:11.615Z", "modified": "2024-01-16T13:48:42.944Z"}, {"entity": "publication", "iuid": "e5f1bff2a04840b1a4bde038251fa843", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e5f1bff2a04840b1a4bde038251fa843.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e5f1bff2a04840b1a4bde038251fa843"}}, "title": "Using null models to compare bacterial and microeukaryotic metacommunity assembly under shifting environmental conditions.", "authors": [{"family": "Vass", "given": "M\u00e1t\u00e9", "initials": "M", "orcid": "0000-0003-0718-7659", "researcher": {"href": "https://publications.scilifelab.se/researcher/6fed30af96e540269edcb565cb34bc39.json"}}, {"family": "Sz\u00e9kely", "given": "Anna J", "initials": "AJ", "orcid": "0000-0001-8063-7156", "researcher": {"href": "https://publications.scilifelab.se/researcher/c9b2d69cfd6a4f41a978b38ddf66c8d5.json"}}, {"family": "Lindstr\u00f6m", "given": "Eva S", "initials": "ES", "orcid": "0000-0001-8920-3071", "researcher": {"href": "https://publications.scilifelab.se/researcher/9290d334ce5a4488b8afd2af511e02ad.json"}}, {"family": "Langenheder", "given": "Silke", "initials": "S", "orcid": "0000-0002-5245-9935", "researcher": {"href": "https://publications.scilifelab.se/researcher/efa9e8f2174a4c7cb903b0f9b895a183.json"}}], "type": "journal article", "published": "2020-02-12", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "2455", "issn-l": "2045-2322"}, "abstract": "Temporal variations in microbial metacommunity structure and assembly processes in response to shifts in environmental conditions are poorly understood. Hence, we conducted a temporal field study by sampling rock pools in four-day intervals during a 5-week period that included strong changes in environmental conditions due to intensive rain. We characterized bacterial and microeukaryote communities by 16S and 18S rRNA gene sequencing, respectively. Using a suite of null model approaches (elements of metacommunity structure, Raup-Crick beta-diversity and quantitative process estimates) to assess dynamics in community assembly, we found that strong changes in environmental conditions induced small but significant temporal changes in assembly processes and triggered different responses in bacterial and microeukaryotic metacommunities, promoting distinct selection processes. Incidence-based approaches showed that the assemblies of both communities were mainly governed by stochastic processes. In contrast, abundance-based methods indicated the dominance of historical contingency and unmeasured factors in the case of bacteria and microeukaryotes, respectively. We distinguished these processes from dispersal-related processes using additional tests. Regardless of the applied null model, our study highlights that community assembly processes are not static, and the relative importance of different assembly processes can vary under different conditions and between different microbial groups.", "doi": "10.1038/s41598-020-59182-1", "pmid": "32051469", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-59182-1"}, {"db": "pmc", "key": "PMC7016149"}], "notes": [], "created": "2020-12-08T23:47:42.006Z", "modified": "2024-01-16T13:48:42.952Z"}, {"entity": "publication", "iuid": "4f91e593c9d848349f62c13e8004a3d6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4f91e593c9d848349f62c13e8004a3d6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4f91e593c9d848349f62c13e8004a3d6"}}, "title": "Quinazoline Ligands Induce Cancer Cell Death through Selective STAT3 Inhibition and G-Quadruplex Stabilization.", "authors": [{"family": "Jamroskovic", "given": "Jan", "initials": "J", "orcid": "0000-0001-6871-7663", "researcher": {"href": "https://publications.scilifelab.se/researcher/154847e2f84f4336a07e219fac6db2f9.json"}}, {"family": "Doimo", "given": "Mara", "initials": "M"}, {"family": "Chand", "given": "Karam", "initials": "K"}, {"family": "Obi", "given": "Ikenna", "initials": "I"}, {"family": "Kumar", "given": "Rajendra", "initials": "R", "orcid": "0000-0002-7268-9519", "researcher": {"href": "https://publications.scilifelab.se/researcher/4ba57d44c650444aa51a030541d3bba7.json"}}, {"family": "Br\u00e4nnstr\u00f6m", "given": "Kristoffer", "initials": "K"}, {"family": "Hedenstr\u00f6m", "given": "Mattias", "initials": "M"}, {"family": "Nath Das", "given": "Rabindra", "initials": "R", "orcid": "0000-0001-6347-2169", "researcher": {"href": "https://publications.scilifelab.se/researcher/fec8d8bcbe8648258cfbab86693c77c6.json"}}, {"family": "Akhunzianov", "given": "Almaz", "initials": "A"}, {"family": "Deiana", "given": "Marco", "initials": "M", "orcid": "0000-0002-7815-4494", "researcher": {"href": "https://publications.scilifelab.se/researcher/f9efbe74ca3940029d782d3ba645fa34.json"}}, {"family": "Kasho", "given": "Kazutoshi", "initials": "K"}, {"family": "Sulis Sato", "given": "Sebastian", "initials": "S"}, {"family": "Pourbozorgi", "given": "Parham L", "initials": "PL"}, {"family": "Mason", "given": "James E", "initials": "JE"}, {"family": "Medini", "given": "Paolo", "initials": "P"}, {"family": "\u00d6hlund", "given": "Daniel", "initials": "D"}, {"family": "Wanrooij", "given": "Sjoerd", "initials": "S"}, {"family": "Chorell", "given": "Erik", "initials": "E", "orcid": "0000-0003-2523-1940", "researcher": {"href": "https://publications.scilifelab.se/researcher/ada783ae0a824621a3b8e1024aae13a4.json"}}, {"family": "Sabouri", "given": "Nasim", "initials": "N", "orcid": "0000-0002-4541-7702", "researcher": {"href": "https://publications.scilifelab.se/researcher/4bdc688dc85a4932acfdfffad8bfc443.json"}}], "type": "journal article", "published": "2020-02-12", "journal": {"volume": "142", "issn": "1520-5126", "issue": "6", "pages": "2876-2888", "title": "J. Am. Chem. Soc.", "issn-l": "0002-7863"}, "abstract": "The signal transducer and activator of transcription 3 (STAT3) protein is a master regulator of most key hallmarks and enablers of cancer, including cell proliferation and the response to DNA damage. G-Quadruplex (G4) structures are four-stranded noncanonical DNA structures enriched at telomeres and oncogenes' promoters. In cancer cells, stabilization of G4 DNAs leads to replication stress and DNA damage accumulation and is therefore considered a promising target for oncotherapy. Here, we designed and synthesized novel quinazoline-based compounds that simultaneously and selectively affect these two well-recognized cancer targets, G4 DNA structures and the STAT3 protein. Using a combination of in vitro assays, NMR, and molecular dynamics simulations, we show that these small, uncharged compounds not only bind to the STAT3 protein but also stabilize G4 structures. In human cultured cells, the compounds inhibit phosphorylation-dependent activation of STAT3 without affecting the antiapoptotic factor STAT1 and cause increased formation of G4 structures, as revealed by the use of a G4 DNA-specific antibody. As a result, treated cells show slower DNA replication, DNA damage checkpoint activation, and an increased apoptotic rate. Importantly, cancer cells are more sensitive to these molecules compared to noncancerous cell lines. This is the first report of a promising class of compounds that not only targets the DNA damage cancer response machinery but also simultaneously inhibits the STAT3-induced cancer cell proliferation, demonstrating a novel approach in cancer therapy.", "doi": "10.1021/jacs.9b11232", "pmid": "31990532", "labels": {"Swedish NMR Centre": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC7307907"}], "notes": [], "created": "2020-01-31T14:38:39.014Z", "modified": "2025-10-17T13:03:57.141Z"}, {"entity": "publication", "iuid": "45731fef896f4c55814ee2668776f539", "links": {"self": {"href": "https://publications.scilifelab.se/publication/45731fef896f4c55814ee2668776f539.json"}, "display": {"href": "https://publications.scilifelab.se/publication/45731fef896f4c55814ee2668776f539"}}, "title": "Subpopulations of extracellular vesicles from human metastatic melanoma tissue identified by quantitative proteomics after optimized isolation.", "authors": [{"family": "Crescitelli", "given": "Rossella", "initials": "R", "orcid": "0000-0002-1714-3169", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d4b955f26ca4a679deb090e30d0ccf1.json"}}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C", "orcid": "0000-0003-1279-1746", "researcher": {"href": "https://publications.scilifelab.se/researcher/e14e17d2cdb24a9f93991d83811c78b9.json"}}, {"family": "Jang", "given": "Su Chul", "initials": "SC", "orcid": "0000-0003-3326-1007", "researcher": {"href": "https://publications.scilifelab.se/researcher/d7866f9f05f74587af9a4d5beec0a1b5.json"}}, {"family": "Cvjetkovic", "given": "Aleksander", "initials": "A", "orcid": "0000-0002-9131-9791", "researcher": {"href": "https://publications.scilifelab.se/researcher/166451e5c8e54c0da297f6238c42c334.json"}}, {"family": "Malmh\u00e4ll", "given": "Carina", "initials": "C"}, {"family": "Karimi", "given": "Nasibeh", "initials": "N"}, {"family": "H\u00f6\u00f6g", "given": "Johanna L", "initials": "JL", "orcid": "0000-0003-2162-3816", "researcher": {"href": "https://publications.scilifelab.se/researcher/f1eaedff964f4060ae6e69f59cad4521.json"}}, {"family": "Johansson", "given": "Iva", "initials": "I", "orcid": "0000-0003-2162-3816", "researcher": {"href": "https://publications.scilifelab.se/researcher/f1eaedff964f4060ae6e69f59cad4521.json"}}, {"family": "Fuchs", "given": "Johannes", "initials": "J"}, {"family": "Thorsell", "given": "Annika", "initials": "A"}, {"family": "Gho", "given": "Yong Song", "initials": "YS"}, {"family": "Olofsson Bagge", "given": "R", "initials": "R", "orcid": "0000-0001-5795-0355", "researcher": {"href": "https://publications.scilifelab.se/researcher/e1f8016d5e64418ca71f230e64e415ba.json"}}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J", "orcid": "0000-0001-9195-9249", "researcher": {"href": "https://publications.scilifelab.se/researcher/0cbcaf6b5698411c92e0de9e8fcf390f.json"}}], "type": "journal article", "published": "2020-02-11", "journal": {"title": "J Extracell Vesicles", "issn": "2001-3078", "volume": "9", "issue": "1", "pages": "1722433", "issn-l": "2001-3078"}, "abstract": "The majority of extracellular vesicle (EV) studies conducted to date have been performed on cell lines with little knowledge on how well these represent the characteristics of EVs in vivo. The aim of this study was to establish a method to isolate and categorize subpopulations of EVs isolated directly from tumour tissue. First we established an isolation protocol for subpopulations of EVs from metastatic melanoma tissue, which included enzymatic treatment (collagenase D and DNase). Small and large EVs were isolated with differential ultracentrifugation, and these were further separated into high and low-density (HD and LD) fractions. All EV subpopulations were then analysed in depth using electron microscopy, Bioanalyzer\u00ae, nanoparticle tracking analysis, and quantitative mass spectrometry analysis. Subpopulations of EVs with distinct size, morphology, and RNA and protein cargo could be isolated from the metastatic melanoma tissue. LD EVs showed an RNA profile with the presence of 18S and 28S ribosomal subunits. In contrast, HD EVs had RNA profiles with small or no peaks for ribosomal RNA subunits. Quantitative proteomics showed that several proteins such as flotillin-1 were enriched in both large and small LD EVs, while ADAM10 were exclusively enriched in small LD EVs. In contrast, mitofilin was enriched only in the large EVs. We conclude that enzymatic treatments improve EV isolation from dense fibrotic tissue without any apparent effect on molecular or morphological characteristics. By providing a detailed categorization of several subpopulations of EVs isolated directly from tumour tissues, we might better understand the function of EVs in tumour biology and their possible use in biomarker discovery.", "doi": "10.1080/20013078.2020.1722433", "pmid": "32128073", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service", "Glycoproteomics and MS Proteomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC7034452"}, {"db": "pii", "key": "1722433"}], "notes": [], "created": "2023-02-16T08:05:59.349Z", "modified": "2024-01-16T13:46:30.980Z"}, {"entity": "publication", "iuid": "7d10557c49554f21b70aaf8ab173723b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7d10557c49554f21b70aaf8ab173723b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7d10557c49554f21b70aaf8ab173723b"}}, "title": "Longitudinal trajectories, correlations and mortality associations of nine biological ages across 20-years follow-up.", "authors": [{"family": "Li", "given": "Xia", "initials": "X", "orcid": "0000-0003-1922-7152", "researcher": {"href": "https://publications.scilifelab.se/researcher/862fd8b41938458f9105c5bb73c35294.json"}}, {"family": "Ploner", "given": "Alexander", "initials": "A", "orcid": "0000-0002-5042-8326", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f1b8cb5cffa4b69b057e2f94ac08d3b.json"}}, {"family": "Wang", "given": "Yunzhang", "initials": "Y"}, {"family": "Magnusson", "given": "Patrik Ke", "initials": "PK"}, {"family": "Reynolds", "given": "Chandra", "initials": "C"}, {"family": "Finkel", "given": "Deborah", "initials": "D"}, {"family": "Pedersen", "given": "Nancy L", "initials": "NL"}, {"family": "Jylh\u00e4v\u00e4", "given": "Juulia", "initials": "J"}, {"family": "H\u00e4gg", "given": "Sara", "initials": "S", "orcid": "0000-0002-2452-1500", "researcher": {"href": "https://publications.scilifelab.se/researcher/e1d010dfe5d84a33b6a6c7ec815ca3dc.json"}}], "type": "journal article", "published": "2020-02-11", "journal": {"title": "Elife", "issn": "2050-084X", "volume": "9", "issue": null, "issn-l": "2050-084X"}, "abstract": "Biological age measurements (BAs) assess aging-related physiological change and predict health risks among individuals of the same chronological age (CA). Multiple BAs have been proposed and are well studied individually but not jointly. We included 845 individuals and 3973 repeated measurements from a Swedish population-based cohort and examined longitudinal trajectories, correlations, and mortality associations of nine BAs across 20 years follow-up. We found the longitudinal growth of functional BAs accelerated around age 70; average levels of BA curves differed by sex across the age span (50-90 years). All BAs were correlated to varying degrees; correlations were mostly explained by CA. Individually, all BAs except for telomere length were associated with mortality risk independently of CA. The largest effects were seen for methylation age estimators (GrimAge) and the frailty index (FI). In joint models, two methylation age estimators (Horvath and GrimAge) and FI remained predictive, suggesting they are complementary in predicting mortality.", "doi": "10.7554/eLife.51507", "pmid": "32041686", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "51507"}, {"db": "pmc", "key": "PMC7012595"}], "notes": [], "created": "2020-02-27T09:21:02.553Z", "modified": "2024-01-16T13:48:42.960Z"}, {"entity": "publication", "iuid": "0d1dc5ac35e34b5593a24d2634f4dbbe", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0d1dc5ac35e34b5593a24d2634f4dbbe.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0d1dc5ac35e34b5593a24d2634f4dbbe"}}, "title": "Whole genome sequencing unveils genetic heterogeneity in optic nerve hypoplasia.", "authors": [{"family": "Dahl", "given": "Sara", "initials": "S", "orcid": "0000-0002-2120-2176", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ef8760a81624f4ca7619d077dab48e6.json"}}, {"family": "Pettersson", "given": "Maria", "initials": "M", "orcid": "0000-0003-3120-1625", "researcher": {"href": "https://publications.scilifelab.se/researcher/bfdfac2208ce4d1a877fa4957e2f4ea4.json"}}, {"family": "Eisfeldt", "given": "Jesper", "initials": "J"}, {"family": "Schr\u00f6der", "given": "Anna Katharina", "initials": "AK"}, {"family": "Wickstr\u00f6m", "given": "Ronny", "initials": "R"}, {"family": "Te\u00e4r Fahnehjelm", "given": "Kristina", "initials": "K"}, {"family": "Anderlid", "given": "Britt-Marie", "initials": "BM"}, {"family": "Lindstrand", "given": "Anna", "initials": "A", "orcid": "0000-0003-0806-5602", "researcher": {"href": "https://publications.scilifelab.se/researcher/07f3e6152da043d38c7a81974fcf8c23.json"}}], "type": "journal article", "published": "2020-02-10", "journal": {"title": "PLoS ONE", "issn": "1932-6203", "volume": "15", "issue": "2", "pages": "e0228622", "issn-l": "1932-6203"}, "abstract": "Optic nerve hypoplasia (ONH) is a congenital malformation with a reduced number of retinal ganglion cell axons in a thin optic nerve. It is a common cause of visual impairment in children and ONH is associated with neurodevelopmental disorders, pituitary hormone deficiencies, and brain malformations. In most cases, the aetiology is unknown, but both environmental factors and genetic causes have been described. This study aimed to identify genetic variants underlying ONH in a well-characterised cohort of individuals with ONH. We performed array comparative genomic hybridization and whole genome sequencing in 29 individuals with ONH. Rare variants were verified by Sanger sequencing and inheritance was assessed in parental samples. We identified 11 rare single nucleotide variants (SNVs) in ten individuals, including a homozygous variant in KIF7 (previously associated with Joubert syndrome), a heterozygous de novo variant in COL4A1 (previously described in an individual with porencephaly), and a homozygous variant in COL4A2. In addition, one individual harboured a heterozygous variant in OPA1 and a heterozygous variant in COL4A1, both were inherited and assessed as variants of unknown clinical significance. Finally, a heterozygous deletion of 341 kb involving exons 7-18 of SOX5 (associated with Lamb-Schaffer syndrome) was identified in one individual. The overall diagnostic yield of pathogenic or likely pathogenic variants in individuals with ONH using whole genome sequencing was 4/29 (14%). Our results show that there is a genetic heterogeneity in ONH and indicate that genetic causes of ONH are not rare. We conclude that genetic testing is valuable in a substantial proportion of the individuals with ONH, especially in cases with non-isolated ONH.", "doi": "10.1371/journal.pone.0228622", "pmid": "32040484", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "PONE-D-19-12114"}, {"db": "pmc", "key": "PMC7010252"}], "notes": [], "created": "2020-07-08T13:05:14.299Z", "modified": "2024-01-16T13:48:42.967Z"}, {"entity": "publication", "iuid": "d8127531635c4d6a9fc5b751ed677f3c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d8127531635c4d6a9fc5b751ed677f3c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d8127531635c4d6a9fc5b751ed677f3c"}}, "title": "Low concentrations of the benzodiazepine drug oxazepam induce anxiolytic effects in wild-caught but not in laboratory zebrafish.", "authors": [{"family": "Vossen", "given": "Laura E", "initials": "LE"}, {"family": "\u010cerven\u00fd", "given": "Daniel", "initials": "D"}, {"family": "Sen Sarma", "given": "Oly", "initials": "O"}, {"family": "Th\u00f6rnqvist", "given": "Per-Ove", "initials": "PO"}, {"family": "Jutfelt", "given": "Fredrik", "initials": "F"}, {"family": "Fick", "given": "Jerker", "initials": "J", "orcid": "0000-0002-3949-7371", "researcher": {"href": "https://publications.scilifelab.se/researcher/523abf923c274066b8bf1439c75ae258.json"}}, {"family": "Brodin", "given": "Tomas", "initials": "T"}, {"family": "Winberg", "given": "Svante", "initials": "S"}], "type": "journal article", "published": "2020-02-10", "journal": {"title": "Sci. Total Environ.", "issn": "1879-1026", "volume": "703", "issue": null, "pages": "134701", "issn-l": "0048-9697"}, "abstract": "Pollution by psychoactive pharmaceuticals has been found to disrupt anti-predator behaviors of wild fish. The challenge is now to identify which of the many psychoactive drugs pose the greatest threat. One strategy is to screen for behavioral effects of selected pharmaceuticals using a single, widely available fish species such as zebrafish. Here, we show that although such high-throughput behavioral screening might facilitate comparisons between pharmaceuticals, the choice of strain is essential. While wild-caught zebrafish exposed to concentrations of the anxiolytic drug oxazepam as low as 0.57 \u03bcg L-1 showed a reduction in the response to conspecific alarm pheromone, laboratory strain AB did not respond to the alarm cue, and consequently, the anxiolytic effect of oxazepam could not be measured. Adaptation to the laboratory environment may have rendered laboratory strains unfit for use in some ecotoxicological and pharmacological studies, since the results might not translate to wild fish populations.", "doi": "10.1016/j.scitotenv.2019.134701", "pmid": "31734507", "labels": {"Genome Engineering Zebrafish": "Service"}, "xrefs": [{"db": "pii", "key": "S0048-9697(19)34692-3"}], "notes": [], "created": "2020-12-10T11:54:13.178Z", "modified": "2021-11-10T12:54:07.360Z"}, {"entity": "publication", "iuid": "bb7a04bc18cd4f11adcb9f73addb3cc5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bb7a04bc18cd4f11adcb9f73addb3cc5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bb7a04bc18cd4f11adcb9f73addb3cc5"}}, "title": "Clinicopathological features and prognostic value of SOX11 in childhood acute lymphoblastic leukemia.", "authors": [{"family": "Gr\u00f6nroos", "given": "Toni", "initials": "T"}, {"family": "M\u00e4kinen", "given": "Artturi", "initials": "A"}, {"family": "Laukkanen", "given": "Saara", "initials": "S"}, {"family": "Mehtonen", "given": "Juha", "initials": "J", "orcid": "0000-0003-0554-4667", "researcher": {"href": "https://publications.scilifelab.se/researcher/d7a49312223a458dbb35c809f20372af.json"}}, {"family": "Nikkil\u00e4", "given": "Atte", "initials": "A"}, {"family": "Oksa", "given": "Laura", "initials": "L"}, {"family": "Rounioja", "given": "Samuli", "initials": "S"}, {"family": "Marincevic-Zuniga", "given": "Yanara", "initials": "Y"}, {"family": "Nordlund", "given": "Jessica", "initials": "J", "orcid": "0000-0001-8699-9959", "researcher": {"href": "https://publications.scilifelab.se/researcher/ddf48c9262134821bcc6ce1180049753.json"}}, {"family": "Pohjolainen", "given": "Virva", "initials": "V"}, {"family": "Paavonen", "given": "Timo", "initials": "T"}, {"family": "Hein\u00e4niemi", "given": "Merja", "initials": "M"}, {"family": "Lohi", "given": "Olli", "initials": "O"}], "type": "journal article", "published": "2020-02-06", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "2043", "issn-l": "2045-2322"}, "abstract": "Acute lymphoblastic leukemia is marked by aberrant transcriptional features that alter cell differentiation, self-renewal, and proliferative features. We sought to identify the transcription factors exhibiting altered and subtype-specific expression patterns in B-ALL and report here that SOX11, a developmental and neuronal transcription factor, is aberrantly expressed in the ETV6-RUNX1 and TCF3-PBX1 subtypes of acute B-cell leukemias. We show that a high expression of SOX11 leads to alterations of gene expression that are typically associated with cell adhesion, migration, and differentiation. A high expression is associated with DNA hypomethylation at the SOX11 locus and a favorable outcome. The results indicate that SOX11 expression marks a group of patients with good outcomes and thereby prompts further study of its use as a biomarker.", "doi": "10.1038/s41598-020-58970-z", "pmid": "32029838", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-58970-z"}, {"db": "pmc", "key": "PMC7005266"}], "notes": [], "created": "2020-02-20T11:30:30.655Z", "modified": "2021-11-10T12:54:08.673Z"}, {"entity": "publication", "iuid": "7e69f131beb747948a82b285b2993442", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7e69f131beb747948a82b285b2993442.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7e69f131beb747948a82b285b2993442"}}, "title": "Clonal competition within complex evolutionary hierarchies shapes AML over time.", "authors": [{"family": "Sand\u00e9n", "given": "Carl", "initials": "C", "orcid": "0000-0002-8931-9565", "researcher": {"href": "https://publications.scilifelab.se/researcher/29207805704e4660b20eebc87efe5282.json"}}, {"family": "Lilljebj\u00f6rn", "given": "Henrik", "initials": "H", "orcid": "0000-0001-8703-1173", "researcher": {"href": "https://publications.scilifelab.se/researcher/b3a75300e8c346858ce8dd8f64ecae85.json"}}, {"family": "Orsmark Pietras", "given": "Christina", "initials": "C"}, {"family": "Henningsson", "given": "Rasmus", "initials": "R"}, {"family": "Saba", "given": "Karim H", "initials": "KH", "orcid": "0000-0003-4946-6488", "researcher": {"href": "https://publications.scilifelab.se/researcher/42cc0dd26f394abb9117550f4e5a034c.json"}}, {"family": "Landberg", "given": "Niklas", "initials": "N", "orcid": "0000-0001-6752-6507", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ad422be3ea44e419662d514ca40cbbe.json"}}, {"family": "Thorsson", "given": "Hanna", "initials": "H"}, {"family": "von Palffy", "given": "Sofia", "initials": "S", "orcid": "0000-0001-5640-4037", "researcher": {"href": "https://publications.scilifelab.se/researcher/594eb39f228241efb0f055799f5eaa88.json"}}, {"family": "Pe\u00f1a-Martinez", "given": "Pablo", "initials": "P", "orcid": "0000-0002-0789-6431", "researcher": {"href": "https://publications.scilifelab.se/researcher/6d675e892dfc4334bb12051e004a7711.json"}}, {"family": "H\u00f6gberg", "given": "Carl", "initials": "C"}, {"family": "Rissler", "given": "Marianne", "initials": "M"}, {"family": "Gisselsson", "given": "David", "initials": "D", "orcid": "0000-0002-0301-426X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3653582762b14f9a9ad2fe6aba511115.json"}}, {"family": "Lazarevic", "given": "Vladimir", "initials": "V", "orcid": "0000-0002-1782-4423", "researcher": {"href": "https://publications.scilifelab.se/researcher/7113f0d0569247d4ac94b73ddc6ca74e.json"}}, {"family": "Juliusson", "given": "Gunnar", "initials": "G"}, {"family": "\u00c5gerstam", "given": "Helena", "initials": "H"}, {"family": "Fioretos", "given": "Thoas", "initials": "T", "orcid": "0000-0002-3235-6154", "researcher": {"href": "https://publications.scilifelab.se/researcher/35a5c1b6023345c6b1317c590bf80680.json"}}], "type": "journal article", "published": "2020-02-05", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "11", "issue": "1", "pages": "579", "issn-l": "2041-1723"}, "abstract": "Clonal heterogeneity and evolution has major implications for disease progression and relapse in acute myeloid leukemia (AML). To model clonal dynamics in vivo, we serially transplanted 23 AML cases to immunodeficient mice and followed clonal composition for up to 15 months by whole-exome sequencing of 84 xenografts across two generations. We demonstrate vast changes in clonality that both progress and reverse over time, and define five patterns of clonal dynamics: Monoclonal, Stable, Loss, Expansion and Burst. We also show that subclonal expansion in vivo correlates with a more adverse prognosis. Furthermore, clonal expansion enabled detection of very rare clones with AML driver mutations that were undetectable by sequencing at diagnosis, demonstrating that the vast majority of AML cases harbor multiple clones already at diagnosis. Finally, the rise and fall of related clones enabled deconstruction of the complex evolutionary hierarchies of the clones that compete to shape AML over time.", "doi": "10.1038/s41467-019-14106-0", "pmid": "32024830", "labels": {"Clinical Genomics Lund": null, "Clinical Genomics": null}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-019-14106-0"}, {"db": "pmc", "key": "PMC7002407"}], "notes": [], "created": "2020-02-24T10:54:40.951Z", "modified": "2021-11-10T12:54:09.856Z"}, {"entity": "publication", "iuid": "53fc32e0ae72487f9138a071ec3fdaba", "links": {"self": {"href": "https://publications.scilifelab.se/publication/53fc32e0ae72487f9138a071ec3fdaba.json"}, "display": {"href": "https://publications.scilifelab.se/publication/53fc32e0ae72487f9138a071ec3fdaba"}}, "title": "A chromosome-scale reference genome for Giardia intestinalis WB.", "authors": [{"family": "Xu", "given": "Feifei", "initials": "F", "orcid": "0000-0003-1946-1520", "researcher": {"href": "https://publications.scilifelab.se/researcher/84c51ec60768479f851e29ebc804f547.json"}}, {"family": "Jex", "given": "Aaron", "initials": "A"}, {"family": "Sv\u00e4rd", "given": "Staffan G", "initials": "SG"}], "type": "dataset", "published": "2020-02-04", "journal": {"title": "Sci Data", "issn": "2052-4463", "volume": "7", "issue": "1", "pages": "38", "issn-l": "2052-4463"}, "abstract": "Giardia intestinalis is a protist causing diarrhea in humans. The first G. intestinalis genome, from the WB isolate, was published more than ten years ago, and has been widely used as the reference genome for Giardia research. However, the genome is fragmented, thus hindering research at the chromosomal level. We re-sequenced the Giardia genome with Pacbio long-read sequencing technology and obtained a new reference genome, which was assembled into near-complete chromosomes with only four internal gaps at long repeats. This new genome is not only more complete but also better annotated at both structural and functional levels, providing more details about gene families, gene organizations and chromosomal structure. This near-complete reference genome will be a valuable resource for the Giardia community and protist research. It also showcases how a fragmented genome can be improved with long-read sequencing technology completed with optical maps.", "doi": "10.1038/s41597-020-0377-y", "pmid": "32019935", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41597-020-0377-y"}, {"db": "pmc", "key": "PMC7000408"}], "notes": [], "created": "2020-02-11T18:48:52.944Z", "modified": "2021-11-10T12:54:10.933Z"}, {"entity": "publication", "iuid": "2f5b1a01cfc945bcbe4a0dad8b6f87a2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2f5b1a01cfc945bcbe4a0dad8b6f87a2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2f5b1a01cfc945bcbe4a0dad8b6f87a2"}}, "title": "Extensive dissemination and intraclonal maturation of HIV Env vaccine-induced B cell responses.", "authors": [{"family": "Phad", "given": "Ganesh E", "initials": "GE", "orcid": "0000-0002-0047-6899", "researcher": {"href": "https://publications.scilifelab.se/researcher/a231cb66fab941df968de8f204c39782.json"}}, {"family": "Pushparaj", "given": "Pradeepa", "initials": "P"}, {"family": "Tran", "given": "Karen", "initials": "K"}, {"family": "Dubrovskaya", "given": "Viktoriya", "initials": "V", "orcid": "0000-0002-6563-0017", "researcher": {"href": "https://publications.scilifelab.se/researcher/58a673f27e224aed933a62c62bc16737.json"}}, {"family": "\u00c0dori", "given": "Monika", "initials": "M"}, {"family": "Martinez-Murillo", "given": "Paola", "initials": "P", "orcid": "0000-0003-0888-3867", "researcher": {"href": "https://publications.scilifelab.se/researcher/63aec47c762643f5b343ada040f1bcaa.json"}}, {"family": "V\u00e1zquez Bernat", "given": "N\u00e9stor", "initials": "N"}, {"family": "Singh", "given": "Suruchi", "initials": "S", "orcid": "0000-0002-4306-9345", "researcher": {"href": "https://publications.scilifelab.se/researcher/fa3266660bdc40e09750af4f22d2ecd5.json"}}, {"family": "Dionne", "given": "Gilman", "initials": "G"}, {"family": "O'Dell", "given": "Sijy", "initials": "S"}, {"family": "Bhullar", "given": "Komal", "initials": "K"}, {"family": "Narang", "given": "Sanjana", "initials": "S"}, {"family": "Sorini", "given": "Chiara", "initials": "C", "orcid": "0000-0002-6803-8377", "researcher": {"href": "https://publications.scilifelab.se/researcher/975173f37f144f06b236817e224de7f0.json"}}, {"family": "Villablanca", "given": "Eduardo J", "initials": "EJ", "orcid": "0000-0001-9522-9729", "researcher": {"href": "https://publications.scilifelab.se/researcher/6c6a2dde2d8f40ef82dfba0cf1b52c0d.json"}}, {"family": "Sundling", "given": "Christopher", "initials": "C", "orcid": "0000-0002-6138-690X", "researcher": {"href": "https://publications.scilifelab.se/researcher/89c1e689a46b4b14adb0dc99e1c0a58c.json"}}, {"family": "Murrell", "given": "Benjamin", "initials": "B"}, {"family": "Mascola", "given": "John R", "initials": "JR"}, {"family": "Shapiro", "given": "Lawrence", "initials": "L"}, {"family": "Pancera", "given": "Marie", "initials": "M"}, {"family": "Martin", "given": "Marcel", "initials": "M"}, {"family": "Corcoran", "given": "Martin", "initials": "M"}, {"family": "Wyatt", "given": "Richard T", "initials": "RT"}, {"family": "Karlsson Hedestam", "given": "Gunilla B", "initials": "GB", "orcid": "0000-0001-7255-9047", "researcher": {"href": "https://publications.scilifelab.se/researcher/ad611ac9c76e44989e585edc4d7ff713.json"}}], "type": "journal article", "published": "2020-02-03", "journal": {"title": "J. Exp. Med.", "issn": "1540-9538", "volume": "217", "issue": "2", "pages": null, "issn-l": "0022-1007"}, "abstract": "Well-ordered HIV-1 envelope glycoprotein (Env) trimers are prioritized for clinical evaluation, and there is a need for an improved understanding about how elicited B cell responses evolve following immunization. To accomplish this, we prime-boosted rhesus macaques with clade C NFL trimers and identified 180 unique Ab lineages from \u223c1,000 single-sorted Env-specific memory B cells. We traced all lineages in high-throughput heavy chain (HC) repertoire (Rep-seq) data generated from multiple immune compartments and time points and expressed several as monoclonal Abs (mAbs). Our results revealed broad dissemination and high levels of somatic hypermutation (SHM) of most lineages, including tier 2 virus neutralizing lineages, following boosting. SHM was highest in the Ab complementarity determining regions (CDRs) but also surprisingly high in the framework regions (FRs), especially FR3. Our results demonstrate the capacity of the immune system to affinity-mature large numbers of Env-specific B cell lineages simultaneously, supporting the use of regimens consisting of repeated boosts to improve each Ab, even those belonging to less expanded lineages.", "doi": "10.1084/jem.20191155", "pmid": "31704807", "labels": {"Bioinformatics Long-term Support WABI": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "jem.20191155"}, {"db": "pmc", "key": "PMC7041718"}], "notes": [], "created": "2021-04-06T10:57:24.634Z", "modified": "2021-11-10T12:54:12.139Z"}, {"entity": "publication", "iuid": "76cc3a61a0034fd98d4b51bbf2930a27", "links": {"self": {"href": "https://publications.scilifelab.se/publication/76cc3a61a0034fd98d4b51bbf2930a27.json"}, "display": {"href": "https://publications.scilifelab.se/publication/76cc3a61a0034fd98d4b51bbf2930a27"}}, "title": "Plasma kidney injury molecule-1 (p-KIM-1) levels and deterioration of kidney function over 16 years.", "authors": [{"family": "Schulz", "given": "Christina-Alexandra", "initials": "CA"}, {"family": "Engstr\u00f6m", "given": "Gunnar", "initials": "G"}, {"family": "Nilsson", "given": "Jan", "initials": "J"}, {"family": "Almgren", "given": "Peter", "initials": "P"}, {"family": "Petkovic", "given": "Marinka", "initials": "M"}, {"family": "Christensson", "given": "Anders", "initials": "A"}, {"family": "Nilsson", "given": "Peter M", "initials": "PM", "orcid": "0000-0002-5652-8459", "researcher": {"href": "https://publications.scilifelab.se/researcher/f23c2a10ac2a4d73a8f62b94855635f1.json"}}, {"family": "Melander", "given": "Olle", "initials": "O"}, {"family": "Orho-Melander", "given": "Marju", "initials": "M"}], "type": "journal article", "published": "2020-02-01", "journal": {"title": "Nephrol Dial Transplant", "issn": "1460-2385", "issn-l": null, "volume": "35", "issue": "2", "pages": "265-273"}, "abstract": "The kidney injury molecule-1 (KIM-1) has previously been associated with kidney function in rodents and humans. Yet its role as a predictive marker for future decline in kidney function has remained less clear.\n\nAt baseline (1991-1994), fasting plasma KIM-1 (p-KIM-1) was measured in 4739 participants of the population-based Malm\u00f6 Diet and Cancer Study. Creatinine and cystatin C were used to calculate estimated glomerular filtration rate (eGFR) according to Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Collaboration 2012 creatinine-cystatin C equation at baseline and follow-up examination (2007-2012). Incident CKD was defined as an eGFR <60 mL/min/1.73 m2 at follow-up.\n\nDuring a mean follow-up time of 16.6 years, high p-KIM-1 levels were associated with a greater decline in eGFR (quartile 1 -1.36 versus quartile 4 -1.54 mL/min/1.73 m2; P < 0.001). In multivariate analyses, the risk for incident CKD at the follow-up examination was higher among participants with baseline p-KIM-1 levels in the highest quartile {odds ratio [OR] 1.45 [95% confidence interval (CI) 1.10-1.92]} compared with those within the lowest quartile. The relative impact of baseline p-KIM-1 on incidence of CKD [OR 1.20 (95% CI 1.08-1.33) per 1 standard deviation (SD) increase in p-KIM-1] was comparable to those of age and systolic blood pressure (SBP) [OR 1.55 (95% CI 1.38-1.74) and OR 1.21 (95% CI 1.09-1.35) per 1 SD increase, respectively]. Adding p-KIM-1 to a conventional risk model resulted in significantly improved C-statistics (P = 0.04) and reclassified 9% of the individuals into the correct risk direction (continuous net reclassification improvement P = 0.02). Furthermore, the risk for hospitalization due to impaired renal function increased with increasing baseline p-KIM-1 [hazard ratio per 1 SD 1.43; (95% CI 1.18-1.74)] during a mean follow-up time of 19.2 years.\n\nOur results show that p-KIM-1 predicts the future decline of eGFR and risk of CKD in healthy middle-aged participants. Whether p-KIM-1 can be used to prioritize preventive action that needs to be further investigated.", "doi": "10.1093/ndt/gfy382", "pmid": "30629206", "labels": {"Clinical Biomarkers": "Service", "PLA and Single Cell Proteomics": "Service", "Affinity Proteomics Uppsala": "Service"}, "xrefs": [{"db": "pii", "key": "5284694"}, {"db": "pmc", "key": "PMC7049260"}], "notes": [], "created": "2020-01-23T16:05:01.488Z", "modified": "2023-04-14T13:55:52.809Z"}, {"entity": "publication", "iuid": "3553724077584c49885e0ab9f66ec2a2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3553724077584c49885e0ab9f66ec2a2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3553724077584c49885e0ab9f66ec2a2"}}, "title": "Glycogenin is Dispensable for Glycogen Synthesis in Human Muscle, and Glycogenin Deficiency Causes Polyglucosan Storage.", "authors": [{"family": "Visuttijai", "given": "Kittichate", "initials": "K", "orcid": "0000-0002-4800-8533", "researcher": {"href": "https://publications.scilifelab.se/researcher/f41f59ad2b0a4e1c95b0cc9cf109f6fa.json"}}, {"family": "Hedberg-Oldfors", "given": "Carola", "initials": "C", "orcid": "0000-0002-7141-4185", "researcher": {"href": "https://publications.scilifelab.se/researcher/dc67028bf0c04f1b9a73bac5e72f9897.json"}}, {"family": "Thomsen", "given": "Christer", "initials": "C"}, {"family": "Glamuzina", "given": "Emma", "initials": "E"}, {"family": "Kornblum", "given": "Cornelia", "initials": "C"}, {"family": "Tasca", "given": "Giorgio", "initials": "G", "orcid": "0000-0003-0849-9144", "researcher": {"href": "https://publications.scilifelab.se/researcher/17e4a6c07f204fb7953350d6b56f3a03.json"}}, {"family": "Hernandez-Lain", "given": "Aurelio", "initials": "A", "orcid": "0000-0002-1933-2238", "researcher": {"href": "https://publications.scilifelab.se/researcher/4b0d26958db04abf8f9240d48a89ec0a.json"}}, {"family": "Sandstedt", "given": "Joakim", "initials": "J", "orcid": "0000-0002-6458-9550", "researcher": {"href": "https://publications.scilifelab.se/researcher/070e186990424c4b83225eb93efc2a66.json"}}, {"family": "Dellgren", "given": "G\u00f6ran", "initials": "G"}, {"family": "Roach", "given": "Peter", "initials": "P"}, {"family": "Oldfors", "given": "Anders", "initials": "A", "orcid": "0000-0003-2523-1414", "researcher": {"href": "https://publications.scilifelab.se/researcher/864bc00c4e234e2aa204e697a9b1d434.json"}}], "type": "journal article", "published": "2020-02-01", "journal": {"title": "J. Clin. Endocrinol. Metab.", "issn": "1945-7197", "volume": "105", "issue": "2", "pages": "557-566", "issn-l": "0021-972X"}, "abstract": "Glycogenin is considered to be an essential primer for glycogen biosynthesis. Nevertheless, patients with glycogenin-1 deficiency due to biallelic GYG1 (NM_004130.3) mutations can store glycogen in muscle. Glycogenin-2 has been suggested as an alternative primer for glycogen synthesis in patients with glycogenin-1 deficiency.\n\nThe objective of this article is to investigate the importance of glycogenin-1 and glycogenin-2 for glycogen synthesis in skeletal and cardiac muscle.\n\nGlycogenin-1 and glycogenin-2 expression was analyzed by Western blot, mass spectrometry, and immunohistochemistry in liver, heart, and skeletal muscle from controls and in skeletal and cardiac muscle from patients with glycogenin-1 deficiency.\n\nGlycogenin-1 and glycogenin-2 both were found to be expressed in the liver, but only glycogenin-1 was identified in heart and skeletal muscle from controls. In patients with truncating GYG1 mutations, neither glycogenin-1 nor glycogenin-2 was expressed in skeletal muscle. However, nonfunctional glycogenin-1 but not glycogenin-2 was identified in cardiac muscle from patients with cardiomyopathy due to GYG1 missense mutations. By immunohistochemistry, the mutated glycogenin-1 colocalized with the storage of glycogen and polyglucosan in cardiomyocytes.\n\nGlycogen can be synthesized in the absence of glycogenin, and glycogenin-1 deficiency is not compensated for by upregulation of functional glycogenin-2. Absence of glycogenin-1 leads to the focal accumulation of glycogen and polyglucosan in skeletal muscle fibers. Expression of mutated glycogenin-1 in the heart is deleterious, and it leads to storage of abnormal glycogen and cardiomyopathy.", "doi": "10.1210/clinem/dgz075", "pmid": "31628455", "labels": {"Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [{"db": "pii", "key": "5599738"}, {"db": "pmc", "key": "PMC7046021"}], "notes": [], "created": "2020-01-30T15:58:42.481Z", "modified": "2024-01-16T13:46:30.988Z"}, {"entity": "publication", "iuid": "2f662c22fce1474b9d17ade9e0181ceb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2f662c22fce1474b9d17ade9e0181ceb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2f662c22fce1474b9d17ade9e0181ceb"}}, "title": "Demography and Natural Selection Have Shaped Genetic Variation in the Widely Distributed Conifer Norway Spruce (Picea abies).", "authors": [{"family": "Wang", "given": "Xi", "initials": "X"}, {"family": "Bernhardsson", "given": "Carolina", "initials": "C"}, {"family": "Ingvarsson", "given": "P\u00e4r K", "initials": "PK", "orcid": "0000-0001-9225-7521", "researcher": {"href": "https://publications.scilifelab.se/researcher/52a2c210ff754465a69f839b40fe8312.json"}}], "type": "journal article", "published": "2020-02-01", "journal": {"title": "Genome Biol Evol", "issn": "1759-6653", "volume": "12", "issue": "2", "pages": "3803-3817", "issn-l": "1759-6653"}, "abstract": "Under the neutral theory, species with larger effective population size are expected to harbor higher genetic diversity. However, across a wide variety of organisms, the range of genetic diversity is orders of magnitude more narrow than the range of effective population size. This observation has become known as Lewontin's paradox and although aspects of this phenomenon have been extensively studied, the underlying causes for the paradox remain unclear. Norway spruce (Picea abies) is a widely distributed conifer species across the northern hemisphere, and it consequently plays a major role in European forestry. Here, we use whole-genome resequencing data from 35 individuals to perform population genomic analyses in P. abies in an effort to understand what drives genome-wide patterns of variation in this species. Despite having a very wide geographic distribution and an corresponding enormous current population size, our analyses find that genetic diversity of P. abies is low across a number of populations (\u03c0 = 0.0049 in Central-Europe, \u03c0 = 0.0063 in Sweden-Norway, \u03c0 = 0.0063 in Finland). To assess the reasons for the low levels of genetic diversity, we infer the demographic history of the species and find that it is characterized by several reoccurring bottlenecks with concomitant decreases in effective population size can, at least partly, provide an explanation for low polymorphism we observe in P. abies. Further analyses suggest that recurrent natural selection, both purifying and positive selection, can also contribute to the loss of genetic diversity in Norway spruce by reducing genetic diversity at linked sites. Finally, the overall low mutation rates seen in conifers can also help explain the low genetic diversity maintained in Norway spruce.", "doi": "10.1093/gbe/evaa005", "pmid": "31958121", "labels": {"NGI Stockholm (Genomics Applications)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "5709816"}, {"db": "pmc", "key": "PMC7046165"}], "notes": [], "created": "2021-01-08T16:29:08.731Z", "modified": "2024-01-16T13:48:42.975Z"}, {"entity": "publication", "iuid": "ae00dd95619c4b038d34abdb141a1384", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ae00dd95619c4b038d34abdb141a1384.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ae00dd95619c4b038d34abdb141a1384"}}, "title": "Convergent Evolution of Hydrogenosomes from Mitochondria by Gene Transfer and Loss.", "authors": [{"family": "Lewis", "given": "William H", "initials": "WH"}, {"family": "Lind", "given": "Anders E", "initials": "AE"}, {"family": "Sendra", "given": "Kacper M", "initials": "KM"}, {"family": "Onsbring", "given": "Henning", "initials": "H"}, {"family": "Williams", "given": "Tom A", "initials": "TA"}, {"family": "Esteban", "given": "Genoveva F", "initials": "GF"}, {"family": "Hirt", "given": "Robert P", "initials": "RP"}, {"family": "Ettema", "given": "Thijs J G", "initials": "TJG"}, {"family": "Embley", "given": "T Martin", "initials": "TM"}], "type": "journal article", "published": "2020-02-01", "journal": {"title": "Mol. Biol. Evol.", "issn": "1537-1719", "issn-l": "0737-4038", "volume": "37", "issue": "2", "pages": "524-539"}, "abstract": "Hydrogenosomes are H2-producing mitochondrial homologs found in some anaerobic microbial eukaryotes that provide a rare intracellular niche for H2-utilizing endosymbiotic archaea. Among ciliates, anaerobic and aerobic lineages are interspersed, demonstrating that the switch to an anaerobic lifestyle with hydrogenosomes has occurred repeatedly and independently. To investigate the molecular details of this transition, we generated genomic and transcriptomic data sets from anaerobic ciliates representing three distinct lineages. Our data demonstrate that hydrogenosomes have evolved from ancestral mitochondria in each case and reveal different degrees of independent mitochondrial genome and proteome reductive evolution, including the first example of complete mitochondrial genome loss in ciliates. Intriguingly, the FeFe-hydrogenase used for generating H2 has a unique domain structure among eukaryotes and appears to have been present, potentially through a single lateral gene transfer from an unknown donor, in the common aerobic ancestor of all three lineages. The early acquisition and retention of FeFe-hydrogenase helps to explain the facility whereby mitochondrial function can be so radically modified within this diverse and ecologically important group of microbial eukaryotes.", "doi": "10.1093/molbev/msz239", "pmid": "31647561", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "5606724"}, {"db": "pmc", "key": "PMC6993867"}], "notes": [], "created": "2020-12-08T23:16:45.895Z", "modified": "2021-11-10T12:54:16.742Z"}, {"entity": "publication", "iuid": "2629beeaf3fe4217aa50a38e5732a8f6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2629beeaf3fe4217aa50a38e5732a8f6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2629beeaf3fe4217aa50a38e5732a8f6"}}, "title": "The antimalarial drug amodiaquine stabilizes p53 through ribosome biogenesis stress, independently of its autophagy-inhibitory activity.", "authors": [{"family": "Espinoza", "given": "Jaime A", "initials": "JA", "orcid": "0000-0002-0731-2715", "researcher": {"href": "https://publications.scilifelab.se/researcher/3cdf2cd80f5b4f87adf6d936b6390ee8.json"}}, {"family": "Zisi", "given": "Asimina", "initials": "A", "orcid": "0000-0002-4253-0275", "researcher": {"href": "https://publications.scilifelab.se/researcher/5cf82380ca6e4cd1985bc9dd23789539.json"}}, {"family": "Kanellis", "given": "Dimitris C", "initials": "DC", "orcid": "0000-0001-8690-2010", "researcher": {"href": "https://publications.scilifelab.se/researcher/0921ab7566514fb0a3cd0daf2baabe6e.json"}}, {"family": "Carreras-Puigvert", "given": "Jordi", "initials": "J"}, {"family": "Henriksson", "given": "Martin", "initials": "M"}, {"family": "H\u00fchn", "given": "Daniela", "initials": "D"}, {"family": "Watanabe", "given": "Kenji", "initials": "K"}, {"family": "Helleday", "given": "Thomas", "initials": "T"}, {"family": "Lindstr\u00f6m", "given": "Mikael S", "initials": "MS", "orcid": "0000-0003-1148-8497", "researcher": {"href": "https://publications.scilifelab.se/researcher/5aa942fbfbee4257a129b3e7888f5b6d.json"}}, {"family": "Bartek", "given": "Jiri", "initials": "J"}], "type": "journal article", "published": "2020-02-00", "journal": {"volume": "27", "issn": "1476-5403", "issue": "2", "pages": "773-789", "title": "Cell Death Differ.", "issn-l": "1350-9047"}, "abstract": "Pharmacological inhibition of ribosome biogenesis is a promising avenue for cancer therapy. Herein, we report a novel activity of the FDA-approved antimalarial drug amodiaquine which inhibits rRNA transcription, a rate-limiting step for ribosome biogenesis, in a dose-dependent manner. Amodiaquine triggers degradation of the catalytic subunit of RNA polymerase I (Pol I), with ensuing RPL5/RPL11-dependent stabilization of p53. Pol I shutdown occurs in the absence of DNA damage and without the subsequent ATM-dependent inhibition of rRNA transcription. RNAseq analysis revealed mechanistic similarities of amodiaquine with BMH-21, the first-in-class Pol I inhibitor, and with chloroquine, the antimalarial analog of amodiaquine, with well-established autophagy-inhibitory activity. Interestingly, autophagy inhibition caused by amodiaquine is not involved in the inhibition of rRNA transcription, suggesting two independent anticancer mechanisms. In vitro, amodiaquine is more efficient than chloroquine in restraining the proliferation of human cell lines derived from colorectal carcinomas, a cancer type with predicted susceptibility to ribosome biogenesis stress. Taken together, our data reveal an unsuspected activity of a drug approved and used in the clinics for over 30 years, and provide rationale for repurposing amodiaquine in cancer therapy.", "doi": "10.1038/s41418-019-0387-5", "pmid": "31285544", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Chemical Biology Consortium Sweden": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41418-019-0387-5"}, {"db": "pmc", "key": "PMC7205879"}], "notes": [], "created": "2019-11-28T13:50:15.354Z", "modified": "2025-10-17T13:04:28.370Z"}, {"entity": "publication", "iuid": "02ca200553534d59a596e532b6a2dddb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/02ca200553534d59a596e532b6a2dddb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/02ca200553534d59a596e532b6a2dddb"}}, "title": "Revealing the Regional Localization and Differential Lung Retention of Inhaled Compounds by Mass Spectrometry Imaging.", "authors": [{"family": "Hamm", "given": "Gregory R", "initials": "GR"}, {"family": "B\u00e4ckstr\u00f6m", "given": "Erica", "initials": "E"}, {"family": "Br\u00fclls", "given": "Mikael", "initials": "M"}, {"family": "Nilsson", "given": "Anna", "initials": "A"}, {"family": "Strittmatter", "given": "Nicole", "initials": "N"}, {"family": "Andr\u00e9n", "given": "Per E", "initials": "PE"}, {"family": "Grime", "given": "Ken", "initials": "K"}, {"family": "Frid\u00e9n", "given": "Markus", "initials": "M"}, {"family": "Goodwin", "given": "Richard J A", "initials": "RJA"}], "type": "comparative study", "published": "2020-02-00", "journal": {"title": "J Aerosol Med Pulm Drug Deliv", "issn": "1941-2703", "volume": "33", "issue": "1", "pages": "43-53", "issn-l": "1941-2711"}, "abstract": "For the treatment of respiratory disease, inhaled drug delivery aims to provide direct access to pharmacological target sites while minimizing systemic exposure. Despite this long-held tenet of inhaled therapeutic advantage, there are limited data of regional drug localization in the lungs after inhalation. The aim of this study was to investigate the distribution and retention of different chemotypes typifying available inhaled drugs [slowly dissolving neutral fluticasone propionate (FP) and soluble bases salmeterol and salbutamol] using mass spectrometry imaging (MSI). Background: Salmeterol, salbutamol, and FP were simultaneously delivered by inhaled nebulization to rats. In the same animals, salmeterol-Methods:d, salbutamol-3d, and FP-3d were delivered by intravenous (IV) injection. Samples of lung tissue were obtained at 2- and 30-minute postdosing, and high-resolution MSI was used to study drug distribution and retention. 3 IV delivery resulted in homogeneous lung distribution for all molecules. In comparison, while inhalation also gave rise to drug presence in the entire lung, there were regional chemotype-dependent areas of higher abundance. At the 30-minute time point, inhaled salmeterol and salbutamol were preferentially retained in bronchiolar tissue, whereas FP was retained in all regions of the lungs. Results: This study clearly demonstrates that inhaled small molecule chemotypes are differentially distributed in lung tissue after inhalation, and that high-resolution MSI can be applied to study these retention patterns.Conclusion:", "doi": "10.1089/jamp.2019.1536", "pmid": "31364961", "labels": {"Spatial Mass Spectrometry": "Collaborative"}, "xrefs": [], "notes": [], "created": "2020-01-24T09:22:48.755Z", "modified": "2021-12-03T11:54:25.057Z"}, {"entity": "publication", "iuid": "0ef79e1b42534802b5fd66e846d4e6da", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0ef79e1b42534802b5fd66e846d4e6da.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0ef79e1b42534802b5fd66e846d4e6da"}}, "title": "Plasma Lipidome and Prediction of Type 2 Diabetes in the Population-Based Malm\u00f6 Diet and Cancer Cohort.", "authors": [{"family": "Fernandez", "given": "C\u00e9line", "initials": "C", "orcid": "0000-0003-1290-4982", "researcher": {"href": "https://publications.scilifelab.se/researcher/0403fdacd924464a913261e53f6e6083.json"}}, {"family": "Surma", "given": "Michal A", "initials": "MA"}, {"family": "Klose", "given": "Christian", "initials": "C"}, {"family": "Gerl", "given": "Mathias J", "initials": "MJ"}, {"family": "Ottosson", "given": "Filip", "initials": "F", "orcid": "0000-0002-8312-3545", "researcher": {"href": "https://publications.scilifelab.se/researcher/14c6874eea0d4fd59677b024c2ca58bf.json"}}, {"family": "Ericson", "given": "Ulrika", "initials": "U"}, {"family": "Oskolkov", "given": "Nikolay", "initials": "N"}, {"family": "Ohro-Melander", "given": "Marju", "initials": "M"}, {"family": "Simons", "given": "Kai", "initials": "K"}, {"family": "Melander", "given": "Olle", "initials": "O"}], "type": "journal article", "published": "2020-02-00", "journal": {"volume": "43", "issn": "1935-5548", "issue": "2", "pages": "366-373", "title": "Diabetes Care", "issn-l": "0149-5992"}, "abstract": "Type 2 diabetes mellitus (T2DM) is associated with dyslipidemia, but the detailed alterations in lipid species preceding the disease are largely unknown. We aimed to identify plasma lipids associated with development of T2DM and investigate their associations with lifestyle.\n\nAt baseline, 178 lipids were measured by mass spectrometry in 3,668 participants without diabetes from the Malm\u00f6 Diet and Cancer Study. The population was randomly split into discovery (n = 1,868, including 257 incident cases) and replication (n = 1,800, including 249 incident cases) sets. We used orthogonal projections to latent structures discriminant analyses, extracted a predictive component for T2DM incidence (lipid-PCDM), and assessed its association with T2DM incidence using Cox regression and lifestyle factors using general linear models.\n\nA T2DM-predictive lipid-PCDM derived from the discovery set was independently associated with T2DM incidence in the replication set, with hazard ratio (HR) among subjects in the fifth versus first quintile of lipid-PCDM of 3.7 (95% CI 2.2-6.5). In comparison, the HR of T2DM among obese versus normal weight subjects was 1.8 (95% CI 1.2-2.6). Clinical lipids did not improve T2DM risk prediction, but adding the lipid-PCDM to all conventional T2DM risk factors increased the area under the receiver operating characteristics curve by 3%. The lipid-PCDM was also associated with a dietary risk score for T2DM incidence and lower level of physical activity.\n\nA lifestyle-related lipidomic profile strongly predicts T2DM development beyond current risk factors. Further studies are warranted to test if lifestyle interventions modifying this lipidomic profile can prevent T2DM.", "doi": "10.2337/dc19-1199", "pmid": "31818810", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "dc19-1199"}], "notes": [], "created": "2020-01-07T22:12:39.038Z", "modified": "2024-01-16T13:48:42.982Z"}, {"entity": "publication", "iuid": "93040a08682f4965ad6b27fe955b74d1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/93040a08682f4965ad6b27fe955b74d1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/93040a08682f4965ad6b27fe955b74d1"}}, "title": "Perspective on CETSA Literature: Toward More Quantitative Data Interpretation.", "authors": [{"family": "Seashore-Ludlow", "given": "Brinton", "initials": "B", "orcid": "0000-0001-8658-5967", "researcher": {"href": "https://publications.scilifelab.se/researcher/4645bc97a8024c548111802101b83571.json"}}, {"family": "Axelsson", "given": "Hanna", "initials": "H"}, {"family": "Lundb\u00e4ck", "given": "Thomas", "initials": "T", "orcid": "0000-0002-8145-7808", "researcher": {"href": "https://publications.scilifelab.se/researcher/e13df787cb884549bcf333aba4e6f010.json"}}], "type": "journal article", "published": "2020-02-00", "journal": {"volume": "25", "issn": "2472-5560", "issue": "2", "pages": "118-126", "title": "SLAS DISCOVERY: Advancing Life Sciences R&D", "issn-l": "2472-5552"}, "abstract": "The cellular thermal shift assay (CETSA) was introduced in 2013 to investigate drug-target engagement inside live cells and tissues. As with all thermal shift assays, the response measured by CETSA is not simply governed by ligand affinity to the investigated target protein, but the thermodynamics and kinetics of ligand binding and protein unfolding also contribute to the observed protein stabilization. This limitation is commonly neglected in current applications of the method to validate the target of small-molecule probes. Instead, there is an eagerness to make direct comparisons of CETSA measurements with functional and phenotypic readouts from cells at 37 \u00b0C. Here, we present a perspective of the early CETSA literature and put the accumulated data into a quantitative context. The analysis includes annotation of ~270 peer-reviewed papers, the majority of which do not consider the underlying biophysical basis of CETSA. We also detail what future technology developments are needed to enable CETSA-based optimization of structure-activity relationships and more appropriate comparisons of these data with functional or phenotypic responses. Finally, we describe ongoing developments in assay formats that allow for CETSA measurements at single-cell resolution, with the aspiration to allow differentiation in cellular target engagement between cells in co-cultures and more complex models, such as organoids and potentially even tissue.", "doi": "10.1177/2472555219884524", "pmid": "31665966", "labels": {"Chemical Biology Consortium Sweden": "Technology development"}, "xrefs": [], "notes": [], "created": "2019-11-07T18:36:29.528Z", "modified": "2025-10-17T13:04:28.381Z"}, {"entity": "publication", "iuid": "8aeb03e392624ccd8794e0fcc8e0eaf3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8aeb03e392624ccd8794e0fcc8e0eaf3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8aeb03e392624ccd8794e0fcc8e0eaf3"}}, "title": "Genomic and transcriptomic features of dermatofibrosarcoma protuberans: Unusual chromosomal origin of the COL1A1-PDGFB fusion gene and synergistic effects of amplified regions in tumor development.", "authors": [{"family": "K\u00f6ster", "given": "Jan", "initials": "J"}, {"family": "Arbajian", "given": "Elsa", "initials": "E"}, {"family": "Viklund", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Isaksson", "given": "Anders", "initials": "A"}, {"family": "Hofvander", "given": "Jakob", "initials": "J"}, {"family": "Haglund", "given": "Felix", "initials": "F"}, {"family": "Bauer", "given": "Henrik", "initials": "H"}, {"family": "Magnusson", "given": "Linda", "initials": "L"}, {"family": "Mandahl", "given": "Nils", "initials": "N"}, {"family": "Mertens", "given": "Fredrik", "initials": "F"}], "type": "journal article", "published": "2020-02-00", "journal": {"title": "Cancer Genet", "issn": "2210-7762", "volume": "241", "issue": null, "pages": "34-41", "issn-l": null}, "abstract": "The dermatofibrosarcoma protuberans family of tumors (DPFT) comprises cutaneous soft tissue neoplasms associated with aberrant PDGFBR signaling, typically through a COL1A1-PDGFB fusion. The aim of the present study was to obtain a better understanding of the chromosomal origin of this fusion and to assess the spectrum of secondary mutations at the chromosome and nucleotide levels. We thus investigated 42 tumor samples from 35 patients using chromosome banding, fluorescence in situ hybridization, single nucleotide polymorphism arrays, and/or massively parallel sequencing (gene panel, whole exome and transcriptome sequencing) methods. We confirmed the age-associated differences in the origin of the COL1A1-PDGFB fusion and could show that it in most cases must arise after DNA synthesis, i.e., in the S or G2 phase of the cell cycle. Whereas there was a non-random pattern of secondary chromosomal rearrangements, single nucleotide variants seem to have little impact on tumor progression. No clear genomic differences between low-grade and high-grade DPFT were found, but the number of chromosomes and chromosomal imbalances as well as the frequency of 9p deletions all tended to be greater among the latter. Gene expression profiling of tumors with COL1A1-PDGFB fusions associated with unbalanced translocations or ring chromosomes identified several transcriptionally up-regulated genes in the amplified regions of chromosomes 17 and 22, including TBX2, PRKCA, MSI2, SOX9, SOX10, and PRAME.", "doi": "10.1016/j.cancergen.2019.12.001", "pmid": "31870844", "labels": {"Clinical Genomics Lund": null, "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": null}, "xrefs": [{"db": "pii", "key": "S2210-7762(19)30319-9"}], "notes": [], "created": "2020-12-02T03:51:59.521Z", "modified": "2024-01-16T13:48:42.988Z"}, {"entity": "publication", "iuid": "d84f7247cb044f92938887130565bd64", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d84f7247cb044f92938887130565bd64.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d84f7247cb044f92938887130565bd64"}}, "title": "Fast time-resolved NMR with non-uniform sampling.", "authors": [{"family": "Go\u0142owicz", "given": "Dariusz", "initials": "D"}, {"family": "Kasprzak", "given": "Pawe\u0142", "initials": "P"}, {"family": "Orekhov", "given": "Vladislav", "initials": "V"}, {"family": "Kazimierczuk", "given": "Krzysztof", "initials": "K"}], "type": "journal article", "published": "2020-02-00", "journal": {"title": "Progress in Nuclear Magnetic Resonance Spectroscopy", "issn": "1873-3301", "volume": "116", "pages": "40-55", "issn-l": "0079-6565"}, "abstract": "NMR spectroscopy is a versatile tool for studying time-dependent processes: chemical reactions, phase transitions or macromolecular structure changes. However, time-resolved NMR is usually based on the simplest among available techniques - one-dimensional spectra serving as \"snapshots\" of the studied process. One of the reasons is that multidimensional experiments are very time-expensive due to costly sampling of evolution time space. In this review we summarize efforts to alleviate the problem of limited applicability of multidimensional NMR in time-resolved studies. We focus on techniques based on sparse or non-uniform sampling (NUS), which lead to experimental time reduction by omitting a significant part of the data during measurement and reconstructing it mathematically, adopting certain assumptions about the spectrum. NUS spectra are faster to acquire than conventional ones and thus better suited to the role of \"snapshots\", but still suffer from non-stationarity of the signal i.e. amplitude and frequency variations within a dataset. We discuss in detail how these instabilities affect the spectra, and what are the optimal ways of sampling the non-stationary FID signal. Finally, we discuss related areas of NMR where serial experiments are exploited and how they can benefit from the same NUS-based approaches.", "doi": "10.1016/j.pnmrs.2019.09.003", "pmid": "32130958", "labels": {"Swedish NMR Centre": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0079-6565(19)30046-9"}], "notes": [], "created": "2023-05-31T16:48:49.125Z", "modified": "2025-10-17T13:03:57.154Z"}, {"entity": "publication", "iuid": "ee2faba8752246c29b1bd90de2630ed5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ee2faba8752246c29b1bd90de2630ed5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ee2faba8752246c29b1bd90de2630ed5"}}, "title": "Exosomes influence the behavior of human mesenchymal stem cells on titanium surfaces.", "authors": [{"family": "Wang", "given": "Xiaoqin", "initials": "X"}, {"family": "Shah", "given": "Furqan A", "initials": "FA"}, {"family": "Vazirisani", "given": "Forugh", "initials": "F"}, {"family": "Johansson", "given": "Anna", "initials": "A"}, {"family": "Palmquist", "given": "Anders", "initials": "A"}, {"family": "Omar", "given": "Omar", "initials": "O"}, {"family": "Ekstr\u00f6m", "given": "Karin", "initials": "K"}, {"family": "Thomsen", "given": "Peter", "initials": "P"}], "type": "journal article", "published": "2020-02-00", "journal": {"title": "Biomaterials", "issn": "1878-5905", "volume": "230", "issue": null, "pages": "119571", "issn-l": "0142-9612"}, "abstract": "Mesenchymal stem cells (MSCs) have important roles during osseointegration. This study determined (i) if MSC-derived extracellular vesicles (EVs)/exosomes can be immobilized on titanium (Ti) surfaces and influence the behavior of MSCs, (ii) if the response is differentially affected by EVs from expanded vs differentiated MSCs and (iii) if the EV protein cargos predict the functional features of the exosomes. EVs secreted by human adipose-derived MSCs were isolated by ultracentrifugation and analyzed using nanoparticle tracking analysis, Western blotting and relative quantitative mass spectrometry. Fluorescence microscopy, scanning electron microscopy, cell counting assay and quantitative polymerase chain reaction were used to analyze MSC adhesion, proliferation and differentiation. Exosome immobilization on Ti promoted MSC adhesion and spreading after 24 h and proliferation after 3 and 6 days, irrespective of whether the exosomes were obtained from expansion or differentiation conditions. Immobilized exosomes upregulated stromal cell-derived factor (SDF-1\u03b1) gene expression. Cell adhesion molecules and signaling molecules were abundant in the exosomal proteome. The predicted functions of the equally-abundant proteins in both exosome types were in line with the observed biological effects mediated by the exosomes. Thus, exosomes derived from MSCs and immobilized on Ti surfaces interact with MSCs and rapidly promote MSC adhesion and proliferation. These findings provide a novel route for modification of titanium implant surfaces.", "doi": "10.1016/j.biomaterials.2019.119571", "pmid": "31753474", "labels": {"Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [{"db": "pii", "key": "S0142-9612(19)30670-2"}], "notes": [], "created": "2020-01-30T15:58:43.390Z", "modified": "2024-01-16T13:46:30.997Z"}, {"entity": "publication", "iuid": "9d8c8b87548b47d385525da2c499b617", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9d8c8b87548b47d385525da2c499b617.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9d8c8b87548b47d385525da2c499b617"}}, "title": "Engineering yeast phospholipid metabolism for de novo oleoylethanolamide production.", "authors": [{"family": "Liu", "given": "Yi", "initials": "Y"}, {"family": "Liu", "given": "Quanli", "initials": "Q"}, {"family": "Krivoruchko", "given": "Anastasia", "initials": "A"}, {"family": "Khoomrung", "given": "Sakda", "initials": "S"}, {"family": "Nielsen", "given": "Jens", "initials": "J", "orcid": "0000-0002-9955-6003", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a596e289be4438a8a2653b1f25fea8b.json"}}], "type": "journal article", "published": "2020-02-00", "journal": {"title": "Nat. Chem. Biol.", "issn": "1552-4469", "volume": "16", "issue": "2", "pages": "197-205", "issn-l": "1552-4450"}, "abstract": "Phospholipids, the most abundant membrane lipid components, are crucial in maintaining membrane structures and homeostasis for biofunctions. As a structurally diverse and tightly regulated system involved in multiple organelles, phospholipid metabolism is complicated to manipulate. Thus, repurposing phospholipids for lipid-derived chemical production remains unexplored. Herein, we develop a Saccharomyces cerevisiae platform for de novo production of oleoylethanolamide, a phospholipid derivative with promising pharmacological applications in ameliorating lipid dysfunction and neurobehavioral symptoms. Through deregulation of phospholipid metabolism, screening of biosynthetic enzymes, engineering of subcellular trafficking and process optimization, we could produce oleoylethanolamide at a titer of 8,115.7 \u00b5g l-1 and a yield on glucose of 405.8 \u00b5g g-1. Our work provides a proof-of-concept study for systemically repurposing phospholipid metabolism for conversion towards value-added biological chemicals, and this multi-faceted framework may shed light on tailoring phospholipid metabolism in other microbial hosts.", "doi": "10.1038/s41589-019-0431-2", "pmid": "31844304", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41589-019-0431-2"}], "notes": [], "created": "2020-01-23T16:07:21.153Z", "modified": "2021-11-10T12:54:25.998Z"}, {"entity": "publication", "iuid": "bcb394512c2e411aa9ce831cde4aa7d9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bcb394512c2e411aa9ce831cde4aa7d9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bcb394512c2e411aa9ce831cde4aa7d9"}}, "title": "Dynamic architecture and regulatory implications of the miRNA network underlying the response to stress in melon.", "authors": [{"family": "Sanz-Carbonell", "given": "Alejandro", "initials": "A", "orcid": "0000-0002-1969-5557", "researcher": {"href": "https://publications.scilifelab.se/researcher/2132a132afcd44ba909dbbb86df6b23a.json"}}, {"family": "Marques", "given": "Maria Carmen", "initials": "MC", "orcid": "0000-0001-8392-453X", "researcher": {"href": "https://publications.scilifelab.se/researcher/e5022479d8564ebb8f59739d5073deb7.json"}}, {"family": "Martinez", "given": "German", "initials": "G", "orcid": "0000-0002-5215-0866", "researcher": {"href": "https://publications.scilifelab.se/researcher/591f629ea8ed44c2bd9cd417dcebd8bc.json"}}, {"family": "Gomez", "given": "Gustavo", "initials": "G", "orcid": "0000-0003-3715-7792", "researcher": {"href": "https://publications.scilifelab.se/researcher/157cf3e864e5415886f9cb9d7f9544c1.json"}}], "type": "journal article", "published": "2020-02-00", "journal": {"title": "RNA Biol", "issn": "1555-8584", "volume": "17", "issue": "2", "pages": "292-308", "issn-l": "1547-6286"}, "abstract": "miRNAs are small RNAs that regulate mRNAs at both transcriptional and posttranscriptional level. In plants, miRNAs are involved in the regulation of different processes including development and stress-response. Elucidating how stress-responsive miRNAs are regulated is key to understand the global response to stress but also to develop efficient biotechnological tools that could help to cope with stress. Here, we describe a computational approach based on sRNA sequencing, transcript quantification and degradome data to analyse the accumulation, function and structural organization of melon miRNAs reactivated under seven biotic and abiotic stress conditions at two and four days post-treatment. Our pipeline allowed us to identify fourteen stress-responsive miRNAs (including evolutionary conserved such as miR156, miR166, miR172, miR319, miR398, miR399, miR894 and miR408) at both analysed times. According to our analysis miRNAs were categorized in three groups showing a broad-, intermediate- or narrow- response range. miRNAs reactive to a broad range of environmental cues appear as central components in the stress-response network. The strictly coordinated response of miR398 and miR408 (broad response-range) to the seven stress treatments during the period analysed here reinforces this notion. Although both, the amplitude and diversity of the miRNA-related response to stress changes during the exposition time, the architecture of the miRNA-network is conserved. This organization of miRNA response to stress is also conserved in rice and soybean supporting the conservation of miRNA-network organization in other crops. Overall, our work sheds light into how miRNA networks in plants organize and function during stress.", "doi": "10.1080/15476286.2019.1697487", "pmid": "31766933", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC6973316"}], "notes": [], "created": "2020-12-08T23:34:40.772Z", "modified": "2021-11-10T12:54:27.181Z"}, {"entity": "publication", "iuid": "1f9840d28baf476e84d9965ddc96549a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1f9840d28baf476e84d9965ddc96549a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1f9840d28baf476e84d9965ddc96549a"}}, "title": "Associations Between Apolipoprotein A1, High-Density Lipoprotein Cholesterol, and Urinary Cytokine Levels in Elderly Males and Females.", "authors": [{"family": "Fellstr\u00f6m", "given": "Bengt", "initials": "B"}, {"family": "Helmersson-Karlqvist", "given": "Johanna", "initials": "J"}, {"family": "Lind", "given": "Lars", "initials": "L"}, {"family": "Soveri", "given": "Inga", "initials": "I"}, {"family": "Wu", "given": "Ping-Hsun", "initials": "PH"}, {"family": "Thulin", "given": "M\u00e5ns", "initials": "M"}, {"family": "\u00c4rnl\u00f6v", "given": "Johan", "initials": "J"}, {"family": "Larsson", "given": "Anders", "initials": "A"}], "type": "journal article", "published": "2020-02-00", "journal": {"title": "Journal of Interferon & Cytokine Research", "issn": "1557-7465", "issn-l": "1079-9907", "volume": "40", "issue": "2", "pages": "71-74"}, "abstract": "There exists a close relationship between cardiovascular diseases and chronic kidney disease. Apolipoprotein A1 and high-density lipoprotein (HDL) cholesterol are widely used as cardiovascular risk markers but they also have anti-inflammatory properties. The aim of this study was to investigate any associations between HDL levels and cytokine levels in urine. We randomly selected 90 urine samples from the Prospective Investigation of the Vasculature in Uppsala Seniors Study (41 males and 49 females). The samples were analyzed with 2 multiplex assays, Multiplex Inflammation I and Cardiovascular II kits (Olink Bioscience, Uppsala, Sweden). We analyzed the correlations between 158 cytokines in urine with apolipoprotein A1, HDL cholesterol, apolipoprotein B, and low-density lipoprotein cholesterol. There were strong correlations for apolipoprotein A1 and HDL cholesterol with individual cytokines. After adjustment for multiplicity testing, there were 33 significant correlations between apolipoprotein A1 and cytokine levels and 14 of these were also significantly correlated with HDL cholesterol. The strongest associations were observed for IL-1\u03b1, SPON2, RAGE, PAR-1, TRAIL-R2, IL-4RA, TNFRSF11A, and SCF. A total of 28 out of 33 correlations were negative, indicating a negative relationship between apolipoprotein A1 and urinary cytokines. The study shows a negative correlation between apolipoprotein A1 and HDL cholesterol and urinary cytokine levels. The finding is in agreement with the anti-inflammatory properties of HDL.", "doi": "10.1089/jir.2019.0074", "pmid": "31599692", "labels": {"Clinical Biomarkers": "Service", "PLA and Single Cell Proteomics": "Service", "Affinity Proteomics Uppsala": "Service"}, "xrefs": [], "notes": [], "created": "2020-01-23T16:04:35.349Z", "modified": "2023-04-14T13:55:53.077Z"}, {"entity": "publication", "iuid": "b22189adeaf145e4a32c95b246088b7b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b22189adeaf145e4a32c95b246088b7b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b22189adeaf145e4a32c95b246088b7b"}}, "title": "Artificial intelligence for diagnosis and grading of prostate cancer in biopsies: a population-based, diagnostic study.", "authors": [{"family": "Str\u00f6m", "given": "Peter", "initials": "P"}, {"family": "Kartasalo", "given": "Kimmo", "initials": "K"}, {"family": "Olsson", "given": "Henrik", "initials": "H"}, {"family": "Solorzano", "given": "Leslie", "initials": "L"}, {"family": "Delahunt", "given": "Brett", "initials": "B"}, {"family": "Berney", "given": "Daniel M", "initials": "DM"}, {"family": "Bostwick", "given": "David G", "initials": "DG"}, {"family": "Evans", "given": "Andrew J", "initials": "AJ"}, {"family": "Grignon", "given": "David J", "initials": "DJ"}, {"family": "Humphrey", "given": "Peter A", "initials": "PA"}, {"family": "Iczkowski", "given": "Kenneth A", "initials": "KA"}, {"family": "Kench", "given": "James G", "initials": "JG"}, {"family": "Kristiansen", "given": "Glen", "initials": "G"}, {"family": "van der Kwast", "given": "Theodorus H", "initials": "TH"}, {"family": "Leite", "given": "Katia R M", "initials": "KRM"}, {"family": "McKenney", "given": "Jesse K", "initials": "JK"}, {"family": "Oxley", "given": "Jon", "initials": "J"}, {"family": "Pan", "given": "Chin-Chen", "initials": "C"}, {"family": "Samaratunga", "given": "Hemamali", "initials": "H"}, {"family": "Srigley", "given": "John R", "initials": "JR"}, {"family": "Takahashi", "given": "Hiroyuki", "initials": "H"}, {"family": "Tsuzuki", "given": "Toyonori", "initials": "T"}, {"family": "Varma", "given": "Murali", "initials": "M"}, {"family": "Zhou", "given": "Ming", "initials": "M"}, {"family": "Lindberg", "given": "Johan", "initials": "J"}, {"family": "Lindskog", "given": "Cecilia", "initials": "C"}, {"family": "Ruusuvuori", "given": "Pekka", "initials": "P"}, {"family": "W\u00e4hlby", "given": "Carolina", "initials": "C", "orcid": "0000-0002-4139-7003", "researcher": {"href": "https://publications.scilifelab.se/researcher/c50194fbc8524d95b7152663ccf17f29.json"}}, {"family": "Gr\u00f6nberg", "given": "Henrik", "initials": "H"}, {"family": "Rantalainen", "given": "Mattias", "initials": "M"}, {"family": "Egevad", "given": "Lars", "initials": "L"}, {"family": "Eklund", "given": "Martin", "initials": "M"}], "type": "journal article", "published": "2020-02-00", "journal": {"title": "Lancet Oncol", "issn": "1474-5488", "issn-l": null, "volume": "21", "issue": "2", "pages": "222-232"}, "abstract": "An increasing volume of prostate biopsies and a worldwide shortage of urological pathologists puts a strain on pathology departments. Additionally, the high intra-observer and inter-observer variability in grading can result in overtreatment and undertreatment of prostate cancer. To alleviate these problems, we aimed to develop an artificial intelligence (AI) system with clinically acceptable accuracy for prostate cancer detection, localisation, and Gleason grading.\r\n\r\nWe digitised 6682 slides from needle core biopsies from 976 randomly selected participants aged 50-69 in the Swedish prospective and population-based STHLM3 diagnostic study done between May 28, 2012, and Dec 30, 2014 (ISRCTN84445406), and another 271 from 93 men from outside the study. The resulting images were used to train deep neural networks for assessment of prostate biopsies. The networks were evaluated by predicting the presence, extent, and Gleason grade of malignant tissue for an independent test dataset comprising 1631 biopsies from 246 men from STHLM3 and an external validation dataset of 330 biopsies from 73 men. We also evaluated grading performance on 87 biopsies individually graded by 23 experienced urological pathologists from the International Society of Urological Pathology. We assessed discriminatory performance by receiver operating characteristics and tumour extent predictions by correlating predicted cancer length against measurements by the reporting pathologist. We quantified the concordance between grades assigned by the AI system and the expert urological pathologists using Cohen's kappa.\r\n\r\nThe AI achieved an area under the receiver operating characteristics curve of 0\u00b7997 (95% CI 0\u00b7994-0\u00b7999) for distinguishing between benign (n=910) and malignant (n=721) biopsy cores on the independent test dataset and 0\u00b7986 (0\u00b7972-0\u00b7996) on the external validation dataset (benign n=108, malignant n=222). The correlation between cancer length predicted by the AI and assigned by the reporting pathologist was 0\u00b796 (95% CI 0\u00b795-0\u00b797) for the independent test dataset and 0\u00b787 (0\u00b784-0\u00b790) for the external validation dataset. For assigning Gleason grades, the AI achieved a mean pairwise kappa of 0\u00b762, which was within the range of the corresponding values for the expert pathologists (0\u00b760-0\u00b773).\r\n\r\nAn AI system can be trained to detect and grade cancer in prostate needle biopsy samples at a ranking comparable to that of international experts in prostate pathology. Clinical application could reduce pathology workload by reducing the assessment of benign biopsies and by automating the task of measuring cancer length in positive biopsy cores. An AI system with expert-level grading performance might contribute a second opinion, aid in standardising grading, and provide pathology expertise in parts of the world where it does not exist.\r\n\r\nSwedish Research Council, Swedish Cancer Society, Swedish eScience Research Center, EIT Health.", "doi": "10.1016/S1470-2045(19)30738-7", "pmid": "31926806", "labels": {"BioImage Informatics": "Service", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pii", "key": "S1470-2045(19)30738-7"}], "notes": [], "created": "2020-11-30T10:32:29.345Z", "modified": "2024-01-16T13:48:42.995Z"}, {"entity": "publication", "iuid": "2a0ff5d5278f4f43a312d4a527ebc89f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2a0ff5d5278f4f43a312d4a527ebc89f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2a0ff5d5278f4f43a312d4a527ebc89f"}}, "title": "Analysis of the genetic variants associated with circulating levels of sgp130. Results from the IMPROVE study.", "authors": [{"family": "Bonomi", "given": "Alice", "initials": "A"}, {"family": "Veglia", "given": "Fabrizio", "initials": "F"}, {"family": "Baldassarre", "given": "Damiano", "initials": "D"}, {"family": "Strawbridge", "given": "Rona J", "initials": "RJ", "orcid": "0000-0001-8506-3585", "researcher": {"href": "https://publications.scilifelab.se/researcher/8ac5060a3b37466dae002d4ad8f4d0ac.json"}}, {"family": "Golabkesh", "given": "Zahra", "initials": "Z"}, {"family": "Sennblad", "given": "Bengt", "initials": "B", "orcid": "0000-0002-4360-8003", "researcher": {"href": "https://publications.scilifelab.se/researcher/1c991150beec46ba8886379193d6037b.json"}}, {"family": "Leander", "given": "Karin", "initials": "K"}, {"family": "Smit", "given": "Andries J", "initials": "AJ"}, {"family": "Giral", "given": "Philippe", "initials": "P"}, {"family": "Humphries", "given": "Steve E", "initials": "SE"}, {"family": "Tremoli", "given": "Elena", "initials": "E"}, {"family": "Hamsten", "given": "Anders", "initials": "A"}, {"family": "de Faire", "given": "Ulf", "initials": "U"}, {"family": "Gigante", "given": "Bruna", "initials": "B", "orcid": "0000-0003-4508-7990", "researcher": {"href": "https://publications.scilifelab.se/researcher/3ac1bdc52e3241ea9eb5645f603229a3.json"}}, {"family": " on behalf of the IMPROVE study group", "given": "", "initials": ""}], "type": "journal article", "published": "2020-02-00", "journal": {"volume": "21", "issn": "1476-5470", "issue": "2", "title": "Genes Immun.", "pages": "100-108", "issn-l": "1466-4879"}, "abstract": "The genes regulating circulating levels of soluble gp130 (sgp130), the antagonist of the inflammatory response in atherosclerosis driven by interleukin 6, are largely unknown. Aims of the present study were to identify genetic loci associated with circulating sgp130 and to explore the potential association between variants associated with sgp130 and markers of subclinical atherosclerosis. The study is based on IMPROVE (n = 3703), a cardiovascular multicentre study designed to investigate the determinants of carotid intima media thickness, a measure of subclinical atherosclerosis. Genomic DNA was genotyped by the CardioMetaboChip and ImmunoChip. About 360,842 SNPs were tested for association with log-transformed sgp130, using linear regression adjusted for age, gender, and population stratification using PLINK v1.07. A p value of 1 \u00d7 10-5 was chosen as threshold for significance value. In an exploratory analysis, SNPs associated with sgp130 were tested for association with c-IMT measures. We identified two SNPs significantly associated with sgp130 levels and 24 showing suggestive association with sgp130 levels. One SNP (rs17688225) on chromosome 14 was positively associated with sgp130 serum levels (\u03b2 = 0.03 SE = 0.007, p = 4.77 \u00d7 10-5) and inversely associated with c-IMT (c-IMTmean-max \u03b2 = -0.001 SE = 0.005, p = 0.0342). Our data indicate that multiple loci regulate sgp130 levels and suggest a possible common pathway between sgp130 and c-IMT measures.", "doi": "10.1038/s41435-019-0090-z", "pmid": "31932740", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41435-019-0090-z"}, {"db": "pmc", "key": "PMC7182533"}], "notes": [], "created": "2020-01-17T08:12:24.951Z", "modified": "2021-11-10T12:54:53.393Z"}, {"entity": "publication", "iuid": "ee719b0f99754255b9e919a7e976953e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ee719b0f99754255b9e919a7e976953e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ee719b0f99754255b9e919a7e976953e"}}, "title": "Painting of Fourth and the X-Linked 1.688 Satellite in D. melanogaster is Involved in Chromosome-Wide Gene Regulation.", "authors": [{"family": "Ekhteraei-Tousi", "given": "Samaneh", "initials": "S"}, {"family": "Lewerentz", "given": "Jacob", "initials": "J"}, {"family": "Larsson", "given": "Jan", "initials": "J"}], "type": "journal article", "published": "2020-01-30", "journal": {"title": "Cells", "issn": "2073-4409", "volume": "9", "issue": "2", "pages": "323", "issn-l": "2073-4409"}, "abstract": "Chromosome-specific regulatory mechanisms provide a model to understand the coordinated regulation of genes on entire chromosomes or on larger genomic regions. In fruit flies, two chromosome-wide systems have been characterized: The male-specific lethal (MSL) complex, which mediates dosage compensation and primarily acts on the male X-chromosome, and Painting of fourth (POF), which governs chromosome-specific regulation of genes located on the 4th chromosome. How targeting of one specific chromosome evolves is still not understood; but repeated sequences, in forms of satellites and transposable elements, are thought to facilitate the evolution of chromosome-specific targeting. The highly repetitive 1.688 satellite has been functionally connected to both these systems. Considering the rapid evolution and the necessarily constant adaptation of regulatory mechanisms, such as dosage compensation, we hypothesised that POF and/or 1.688 may still show traces of dosage-compensation functions. Here, we test this hypothesis by transcriptome analysis. We show that loss of Pof decreases not only chromosome 4 expression but also reduces the X-chromosome expression in males. The 1.688 repeat deletion, Zhr1 (Zygotic hybrid rescue), does not affect male dosage compensation detectably; however, Zhr1 in females causes a stimulatory effect on X-linked genes with a strong binding affinity to the MSL complex (genes close to high-affinity sites). Lack of pericentromeric 1.688 also affected 1.688 expression in trans and was linked to the differential expression of genes involved in eggshell formation. We discuss our results with reference to the connections between POF, the 1.688 satellite and dosage compensation, and the role of the 1.688 satellite in hybrid lethality.", "doi": "10.3390/cells9020323", "pmid": "32019091", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "cells9020323"}, {"db": "pmc", "key": "PMC7072490"}], "notes": [], "created": "2020-07-08T13:05:15.076Z", "modified": "2024-01-16T13:48:43.003Z"}, {"entity": "publication", "iuid": "18df90c9313348749d18bfcfc7334742", "links": {"self": {"href": "https://publications.scilifelab.se/publication/18df90c9313348749d18bfcfc7334742.json"}, "display": {"href": "https://publications.scilifelab.se/publication/18df90c9313348749d18bfcfc7334742"}}, "title": "Diversity and Host Interactions Among Virulent and Temperate Baltic Sea Flavobacterium Phages.", "authors": [{"family": "Nilsson", "given": "Emelie", "initials": "E"}, {"family": "Bayfield", "given": "Oliver W", "initials": "OW", "orcid": "0000-0003-1421-7780", "researcher": {"href": "https://publications.scilifelab.se/researcher/bb071bf951644667b670a0c00f869e46.json"}}, {"family": "Lundin", "given": "Daniel", "initials": "D", "orcid": "0000-0002-8779-6464", "researcher": {"href": "https://publications.scilifelab.se/researcher/227cc90e084348a193fee05eb23a6bf3.json"}}, {"family": "Antson", "given": "Alfred A", "initials": "AA", "orcid": "0000-0002-4533-3816", "researcher": {"href": "https://publications.scilifelab.se/researcher/42b5a7cd8d044d3298e8e93eb9af1a76.json"}}, {"family": "Holmfeldt", "given": "Karin", "initials": "K"}], "type": "journal article", "published": "2020-01-30", "journal": {"title": "Viruses", "issn": "1999-4915", "volume": "12", "issue": "2", "pages": "158", "issn-l": "1999-4915"}, "abstract": "Viruses in aquatic environments play a key role in microbial population dynamics and nutrient cycling. In particular, bacteria of the phylum Bacteriodetes are known to participate in recycling algal blooms. Studies of phage-host interactions involving this phylum are hence important to understand the processes shaping bacterial and viral communities in the ocean as well as nutrient cycling. In this study, we isolated and sequenced three strains of flavobacteria-LMO6, LMO9, LMO8-and 38 virulent phages infecting them. These phages represent 15 species, occupying three novel genera. Additionally, one temperate phage was induced from LMO6 and was found to be competent at infecting LMO9. Functions could be predicted for a limited number of phage genes, mainly representing roles in DNA replication and virus particle formation. No metabolic genes were detected. While the phages isolated on LMO8 could infect all three bacterial strains, the LMO6 and LMO9 phages could not infect LMO8. Of the phages isolated on LMO9, several showed a host-derived reduced efficiency of plating on LMO6, potentially due to differences in DNA methyltransferase genes. Overall, these phage-host systems contribute novel genetic information to our sequence databases and present valuable tools for the study of both virulent and temperate phages.", "doi": "10.3390/v12020158", "pmid": "32019073", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "v12020158"}, {"db": "pmc", "key": "PMC7077304"}], "notes": [], "created": "2020-07-08T13:05:17.299Z", "modified": "2024-01-16T13:48:43.010Z"}, {"entity": "publication", "iuid": "2327daa01a69409ebeaa040fe7f5fbd3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2327daa01a69409ebeaa040fe7f5fbd3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2327daa01a69409ebeaa040fe7f5fbd3"}}, "title": "Sarek: A portable workflow for whole-genome sequencing analysis of germline and somatic variants.", "authors": [{"family": "Garcia", "given": "Maxime", "initials": "M", "orcid": "0000-0003-2827-9261", "researcher": {"href": "https://publications.scilifelab.se/researcher/8cf9b1b223f04296adcb6bd091c548de.json"}}, {"family": "Juhos", "given": "Szilveszter", "initials": "S"}, {"family": "Larsson", "given": "Malin", "initials": "M"}, {"family": "Olason", "given": "Pall I", "initials": "PI"}, {"family": "Martin", "given": "Marcel", "initials": "M", "orcid": "0000-0002-0680-200X", "researcher": {"href": "https://publications.scilifelab.se/researcher/132afd4fea2e4e86bdf43708c8f49907.json"}}, {"family": "Eisfeldt", "given": "Jesper", "initials": "J", "orcid": "0000-0003-3716-4917", "researcher": {"href": "https://publications.scilifelab.se/researcher/32a701ee07674785b48b047665e18ee6.json"}}, {"family": "DiLorenzo", "given": "Sebastian", "initials": "S"}, {"family": "Sandgren", "given": "Johanna", "initials": "J"}, {"family": "D\u00edaz De St\u00e5hl", "given": "Teresita", "initials": "T"}, {"family": "Ewels", "given": "Philip", "initials": "P", "orcid": "0000-0003-4101-2502", "researcher": {"href": "https://publications.scilifelab.se/researcher/9d0fd82fe18b41539a761c55075f31d6.json"}}, {"family": "Wirta", "given": "Valtteri", "initials": "V", "orcid": "0000-0003-3811-5439", "researcher": {"href": "https://publications.scilifelab.se/researcher/cba024b2e3c347f6b981922d984ad2d6.json"}}, {"family": "Nist\u00e9r", "given": "Monica", "initials": "M", "orcid": "0000-0002-1261-3790", "researcher": {"href": "https://publications.scilifelab.se/researcher/e1dc80e61f574293a190f2f3ef464988.json"}}, {"family": "K\u00e4ller", "given": "Max", "initials": "M", "orcid": "0000-0001-6813-3051", "researcher": {"href": "https://publications.scilifelab.se/researcher/536ad902a272482aba853c078557e240.json"}}, {"family": "Nystedt", "given": "Bj\u00f6rn", "initials": "B", "orcid": "0000-0001-7809-7664", "researcher": {"href": "https://publications.scilifelab.se/researcher/f0af5a168baa4b00a6fab8d3447ebfb4.json"}}], "type": "journal article", "published": "2020-01-29", "journal": {"volume": "9", "issn": "2046-1402", "issue": null, "pages": "63", "title": "F1000Res", "issn-l": "2046-1402"}, "abstract": "Whole-genome sequencing (WGS) is a fundamental technology for research to advance precision medicine, but the limited availability of portable and user-friendly workflows for WGS analyses poses a major challenge for many research groups and hampers scientific progress. Here we present Sarek, an open-source workflow to detect germline variants and somatic mutations based on sequencing data from WGS, whole-exome sequencing (WES), or gene panels. Sarek features (i) easy installation, (ii) robust portability across different computer environments, (iii) comprehensive documentation, (iv) transparent and easy-to-read code, and (v) extensive quality metrics reporting. Sarek is implemented in the Nextflow workflow language and supports both Docker and Singularity containers as well as Conda environments, making it ideal for easy deployment on any POSIX-compatible computers and cloud compute environments. Sarek follows the GATK best-practice recommendations for read alignment and pre-processing, and includes a wide range of software for the identification and annotation of germline and somatic single-nucleotide variants, insertion and deletion variants, structural variants, tumour sample purity, and variations in ploidy and copy number. Sarek offers easy, efficient, and reproducible WGS analyses, and can readily be used both as a production workflow at sequencing facilities and as a powerful stand-alone tool for individual research groups. The Sarek source code, documentation and installation instructions are freely available at https://github.com/nf-core/sarek and at https://nf-co.re/sarek/.", "doi": "10.12688/f1000research.16665.2", "pmid": "32269765", "labels": {"Bioinformatics Support, Infrastructure and Training": "Technology development", "Bioinformatics Long-term Support WABI": "Technology development", "NGI Stockholm (Genomics Production)": "Service", "National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Clinical Genomics Stockholm": "Collaborative", "Bioinformatics Support and Infrastructure": "Technology development", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Technology development", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC7111497"}], "notes": [], "created": "2020-04-23T08:58:58.026Z", "modified": "2024-01-16T13:48:43.022Z"}, {"entity": "publication", "iuid": "760bf7172ce74b69be827d62680c875a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/760bf7172ce74b69be827d62680c875a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/760bf7172ce74b69be827d62680c875a"}}, "title": "The round goby genome provides insights into mechanisms that may facilitate biological invasions.", "authors": [{"family": "Adrian-Kalchhauser", "given": "Irene", "initials": "I", "orcid": "0000-0002-7563-2577", "researcher": {"href": "https://publications.scilifelab.se/researcher/a81e38f709b54ce48c1381c9bf94c360.json"}}, {"family": "Blomberg", "given": "Anders", "initials": "A"}, {"family": "Larsson", "given": "Tomas", "initials": "T"}, {"family": "Musilova", "given": "Zuzana", "initials": "Z"}, {"family": "Peart", "given": "Claire R", "initials": "CR"}, {"family": "Pippel", "given": "Martin", "initials": "M"}, {"family": "Solbakken", "given": "Monica Hongroe", "initials": "MH"}, {"family": "Suurv\u00e4li", "given": "Jaanus", "initials": "J"}, {"family": "Walser", "given": "Jean-Claude", "initials": "J"}, {"family": "Wilson", "given": "Joanna Yvonne", "initials": "JY"}, {"family": "Alm Rosenblad", "given": "Magnus", "initials": "M"}, {"family": "Burguera", "given": "Demian", "initials": "D"}, {"family": "Gutnik", "given": "Silvia", "initials": "S"}, {"family": "Michiels", "given": "Nico", "initials": "N"}, {"family": "T\u00f6pel", "given": "Mats", "initials": "M"}, {"family": "Pankov", "given": "Kirill", "initials": "K"}, {"family": "Schloissnig", "given": "Siegfried", "initials": "S"}, {"family": "Winkler", "given": "Sylke", "initials": "S"}], "type": "journal article", "published": "2020-01-28", "journal": {"title": "BMC Biol.", "issn": "1741-7007", "issn-l": "1741-7007", "volume": "18", "issue": "1", "pages": "11"}, "abstract": "The invasive benthic round goby (Neogobius melanostomus) is the most successful temperate invasive fish and has spread in aquatic ecosystems on both sides of the Atlantic. Invasive species constitute powerful in situ experimental systems to study fast adaptation and directional selection on short ecological timescales and present promising case studies to understand factors involved the impressive ability of some species to colonize novel environments. We seize the unique opportunity presented by the round goby invasion to study genomic substrates potentially involved in colonization success.\r\n\r\nWe report a highly contiguous long-read-based genome and analyze gene families that we hypothesize to relate to the ability of these fish to deal with novel environments. The analyses provide novel insights from the large evolutionary scale to the small species-specific scale. We describe expansions in specific cytochrome P450 enzymes, a remarkably diverse innate immune system, an ancient duplication in red light vision accompanied by red skin fluorescence, evolutionary patterns of epigenetic regulators, and the presence of osmoregulatory genes that may have contributed to the round goby's capacity to invade cold and salty waters. A recurring theme across all analyzed gene families is gene expansions.\r\n\r\nThe expanded innate immune system of round goby may potentially contribute to its ability to colonize novel areas. Since other gene families also feature copy number expansions in the round goby, and since other Gobiidae also feature fascinating environmental adaptations and are excellent colonizers, further long-read genome approaches across the goby family may reveal whether gene copy number expansions are more generally related to the ability to conquer new habitats in Gobiidae or in fish.", "doi": "10.1186/s12915-019-0731-8", "pmid": "31992286", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1186/s12915-019-0731-8"}, {"db": "pmc", "key": "PMC6988351"}], "notes": [], "created": "2021-12-14T13:57:05.426Z", "modified": "2024-01-16T13:48:43.029Z"}, {"entity": "publication", "iuid": "796149f9eb4f4e3980d73a2969461850", "links": {"self": {"href": "https://publications.scilifelab.se/publication/796149f9eb4f4e3980d73a2969461850.json"}, "display": {"href": "https://publications.scilifelab.se/publication/796149f9eb4f4e3980d73a2969461850"}}, "title": "Building de novo reference genome assemblies of complex eukaryotic microorganisms from single nuclei.", "authors": [{"family": "Montoliu-Nerin", "given": "Merce", "initials": "M", "orcid": "0000-0002-5200-0411", "researcher": {"href": "https://publications.scilifelab.se/researcher/7f89e94a04c6429db7e706b4d8d6626a.json"}}, {"family": "S\u00e1nchez-Garc\u00eda", "given": "Marisol", "initials": "M", "orcid": "0000-0002-0635-6281", "researcher": {"href": "https://publications.scilifelab.se/researcher/5ccb3584fa144e178750ff2fc4666cfe.json"}}, {"family": "Bergin", "given": "Claudia", "initials": "C"}, {"family": "Grabherr", "given": "Manfred", "initials": "M"}, {"family": "Ellis", "given": "Barbara", "initials": "B"}, {"family": "Kutschera", "given": "Verena Esther", "initials": "VE", "orcid": "0000-0002-8930-534X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4f80fb4d234c4f2fa2179ad1e7c6a6db.json"}}, {"family": "Kierczak", "given": "Marcin", "initials": "M"}, {"family": "Johannesson", "given": "Hanna", "initials": "H"}, {"family": "Rosling", "given": "Anna", "initials": "A", "orcid": "0000-0002-7003-5941", "researcher": {"href": "https://publications.scilifelab.se/researcher/c4c4bbb9e6c343808e8fa9345b7c05b2.json"}}], "type": "journal article", "published": "2020-01-28", "journal": {"title": "Sci Rep", "issn": "2045-2322", "issn-l": "2045-2322", "volume": "10", "issue": "1", "pages": "1303"}, "abstract": "The advent of novel sequencing techniques has unraveled a tremendous diversity on Earth. Genomic data allow us to understand ecology and function of organisms that we would not otherwise know existed. However, major methodological challenges remain, in particular for multicellular organisms with large genomes. Arbuscular mycorrhizal (AM) fungi are important plant symbionts with cryptic and complex multicellular life cycles, thus representing a suitable model system for method development. Here, we report a novel method for large scale, unbiased nuclear sorting, sequencing, and de novo assembling of AM fungal genomes. After comparative analyses of three assembly workflows we discuss how sequence data from single nuclei can best be used for different downstream analyses such as phylogenomics and comparative genomics of single nuclei. Based on analysis of completeness, we conclude that comprehensive de novo genome assemblies can be produced from six to seven nuclei. The method is highly applicable for a broad range of taxa, and will greatly improve our ability to study multicellular eukaryotes with complex life cycles.", "doi": "10.1038/s41598-020-58025-3", "pmid": "31992756", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Microbial Single Cell Genomics": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Support and Infrastructure": "Service", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-58025-3"}, {"db": "pmc", "key": "PMC6987183"}], "notes": [], "created": "2020-02-03T10:35:42.153Z", "modified": "2024-01-16T13:48:43.036Z"}, {"entity": "publication", "iuid": "bea2a6c152d74b7a8b9703f4e41bfb79", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bea2a6c152d74b7a8b9703f4e41bfb79.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bea2a6c152d74b7a8b9703f4e41bfb79"}}, "title": "Population Pharmacokinetics and Pharmacogenetics of Ethambutol in Adult Patients Coinfected with Tuberculosis and HIV.", "authors": [{"family": "Sundell", "given": "Jesper", "initials": "J", "orcid": "0000-0002-5395-9819", "researcher": {"href": "https://publications.scilifelab.se/researcher/8dba5ed8dd254a5b9f09cb89f3dda721.json"}}, {"family": "Bienvenu", "given": "Emile", "initials": "E"}, {"family": "Birgersson", "given": "Sofia", "initials": "S"}, {"family": "\u00c4bel\u00f6", "given": "Angela", "initials": "A"}, {"family": "Ashton", "given": "Michael", "initials": "M"}], "type": "journal article", "published": "2020-01-27", "journal": {"title": "Antimicrob. Agents Chemother.", "issn": "1098-6596", "issn-l": "0066-4804", "volume": "64", "issue": "2", "pages": null}, "abstract": "This study aimed to characterize the population pharmacokinetics and pharmacogenetics of ethambutol in tuberculosis-HIV-coinfected adult patients. Ethambutol plasma concentrations, determined by liquid chromatography-tandem mass spectrometry, in 63 patients receiving ethambutol as part of rifampin-based fixed-dose combination therapy for tuberculosis were analyzed using nonlinear mixed-effects modeling. A one-compartment disposition model with first-order elimination and four transit compartments prior to first-order absorption was found to adequately describe the concentration-time profiles of ethambutol in plasma. Body weight was implemented as an allometric function on the clearance and volume parameters. Estimates of oral clearance and volume of distribution were 77.4 liters/h and 76.2 liters, respectively. A G/A mutation with regard to CYP1A2 2159 G>A was associated with a 50% reduction in relative bioavailability. Simulations revealed that doses of 30 mg/kg of body weight and 50 mg/kg for G/G and G/A carriers, respectively, would result in clinically adequate exposure. The results presented here suggest that CYP1A2 polymorphism affects ethambutol exposure in this population and that current treatment guidelines may result in underexposure in patients coinfected with tuberculosis and HIV. Based on simulations, a dose increase from15 to 20 mg/kg to 30 mg/kg is suggested. However, the 50-mg/kg dose required to reach therapeutic exposure in G/A carriers may be inappropriate due to the dose-dependent toxicity of ethambutol. Additional studies are required to further investigate CYP450 polymorphism effects on ethambutol pharmacokinetics.", "doi": "10.1128/AAC.01583-19", "pmid": "31712201", "labels": {"NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pii", "key": "AAC.01583-19"}, {"db": "pmc", "key": "PMC6985744"}], "notes": [], "created": "2021-01-14T11:59:21.203Z", "modified": "2021-12-07T13:56:13.923Z"}, {"entity": "publication", "iuid": "2fbb3c01bdfc42fcb76d81c03118c91a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2fbb3c01bdfc42fcb76d81c03118c91a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2fbb3c01bdfc42fcb76d81c03118c91a"}}, "title": "Transcriptomic profiling of skeletal muscle adaptations to exercise and inactivity.", "authors": [{"family": "Pillon", "given": "Nicolas J", "initials": "NJ", "orcid": "0000-0003-1107-9490", "researcher": {"href": "https://publications.scilifelab.se/researcher/4b917d3e521149ec9d695c62ac2d1b85.json"}}, {"family": "Gabriel", "given": "Brendan M", "initials": "BM", "orcid": "0000-0001-6878-8779", "researcher": {"href": "https://publications.scilifelab.se/researcher/1fa7198e43f648b5ab2da4d43f71962d.json"}}, {"family": "Dollet", "given": "Lucile", "initials": "L"}, {"family": "Smith", "given": "Jonathon A B", "initials": "JAB", "orcid": "0000-0003-2452-1655", "researcher": {"href": "https://publications.scilifelab.se/researcher/bffd42f562b3485fb50090c02aceeaef.json"}}, {"family": "Sard\u00f3n Puig", "given": "Laura", "initials": "L", "orcid": "0000-0002-0481-4023", "researcher": {"href": "https://publications.scilifelab.se/researcher/73c9841603dc43edae07c7e606776225.json"}}, {"family": "Botella", "given": "Javier", "initials": "J", "orcid": "0000-0001-9722-8519", "researcher": {"href": "https://publications.scilifelab.se/researcher/199f6b058cb342b391566273dc4faf78.json"}}, {"family": "Bishop", "given": "David J", "initials": "DJ", "orcid": "0000-0002-6956-9188", "researcher": {"href": "https://publications.scilifelab.se/researcher/ecaa5fe4ab9649c8a90ae1fed84a222e.json"}}, {"family": "Krook", "given": "Anna", "initials": "A", "orcid": "0000-0002-0891-0258", "researcher": {"href": "https://publications.scilifelab.se/researcher/f43339bcd571486b845a3b10e241bcc4.json"}}, {"family": "Zierath", "given": "Juleen R", "initials": "JR", "orcid": "0000-0001-6891-7497", "researcher": {"href": "https://publications.scilifelab.se/researcher/f4ef2b94ba2d44dd9b41192567a7af53.json"}}], "type": "journal article", "published": "2020-01-24", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "11", "issue": "1", "pages": "470"}, "abstract": "The molecular mechanisms underlying the response to exercise and inactivity are not fully understood. We propose an innovative approach to profile the skeletal muscle transcriptome to exercise and inactivity using 66 published datasets. Data collected from human studies of aerobic and resistance exercise, including acute and chronic exercise training, were integrated using meta-analysis methods (www.metamex.eu). Here we use gene ontology and pathway analyses to reveal selective pathways activated by inactivity, aerobic versus resistance and acute versus chronic exercise training. We identify NR4A3 as one of the most exercise- and inactivity-responsive genes, and establish a role for this nuclear receptor in mediating the metabolic responses to exercise-like stimuli in vitro. The meta-analysis (MetaMEx) also highlights the differential response to exercise in individuals with metabolic impairments. MetaMEx provides the most extensive dataset of skeletal muscle transcriptional responses to different modes of exercise and an online interface to readily interrogate the database.", "doi": "10.1038/s41467-019-13869-w", "pmid": "31980607", "labels": {"Bioinformatics Support, Infrastructure and Training": "Service", "Bioinformatics Support and Infrastructure": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-019-13869-w"}, {"db": "pmc", "key": "PMC6981202"}], "notes": [], "created": "2020-01-07T15:03:10.909Z", "modified": "2021-11-10T12:54:37.387Z"}, {"entity": "publication", "iuid": "16e7c5665cf14e328840eea4893d4af6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/16e7c5665cf14e328840eea4893d4af6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/16e7c5665cf14e328840eea4893d4af6"}}, "title": "Extracellular Vesicles Released From the Skin Commensal Yeast Malassezia sympodialis Activate Human Primary Keratinocytes.", "authors": [{"family": "Vallhov", "given": "Helen", "initials": "H"}, {"family": "Johansson", "given": "Catharina", "initials": "C"}, {"family": "Veerman", "given": "Rosanne E", "initials": "RE"}, {"family": "Scheynius", "given": "Annika", "initials": "A"}], "type": "journal article", "published": "2020-01-24", "journal": {"title": "Front. Cell. Infect. Microbiol.", "issn": "2235-2988", "volume": "10", "issue": null, "pages": "6", "issn-l": "2235-2988"}, "abstract": "Extracellular vesicles (EVs) released from fungi have been shown to participate in inter-organismal communication and in cross-kingdom modulation of host defense. Malassezia species are the dominant commensal fungal members of the human skin microbiota. We have previously found that Malassezia sympodialis releases EVs. These EVs, designated MalaEx, carry M. sympodialis allergens and induce a different inflammatory cytokine response in peripheral blood mononuclear cells (PBMC) from patients with atopic dermatitis compared to healthy controls. In this study, we explored the host-microbe interaction between MalaEx and human keratinocytes with the hypothesis that MalaEx might be able to activate human keratinocytes to express the intercellular adhesion molecule-1 (ICAM-1, CD54). MalaEx were prepared from M. sympodialis (ATCC 42132) culture supernatants by a combination of centrifugation, filtration and serial ultracentrifugation. The MalaEx showed a size range of 70-580 nm with a mean of 154 nm using nanoparticle tracking analysis. MalaEx were found to induce a significant up-regulation of ICAM-1 expression on primary human keratinocytes isolated from human ex vivo skin (p = 0.026, n = 3), compared to the unstimulated keratinocytes. ICAM-1 is a counter ligand for the leukocyte integrins lymphocyte function-associated antigen-1 (LFA-1) and macrophage-1 antigen (Mac-1), of which induced expression on epithelial cells leads to the attraction of immune competent cells. Thus, the capacity of MalaEx to activate keratinocytes with an enhanced ICAM-1 expression indicates an important step in the cutaneous defense against M. sympodialis. How this modulation of host cells by a fungus is balanced between the commensal, pathogenic, or beneficial states on the skin in the interplay with the host needs to be further elucidated.", "doi": "10.3389/fcimb.2020.00006", "pmid": "32039038", "labels": {"Integrated Microscopy Technologies Stockholm": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC6993562"}], "notes": [], "created": "2020-12-08T20:43:44.583Z", "modified": "2024-01-16T13:48:43.043Z"}, {"entity": "publication", "iuid": "7aa9a011dfae4264bb5ed7dbf3b4c135", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7aa9a011dfae4264bb5ed7dbf3b4c135.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7aa9a011dfae4264bb5ed7dbf3b4c135"}}, "title": "Estimating Detection Limits of Potentiometric DNA Sensors Using Surface Plasmon Resonance Analyses.", "authors": [{"family": "Xu", "given": "Xingxing", "initials": "X", "orcid": "0000-0002-1769-4382", "researcher": {"href": "https://publications.scilifelab.se/researcher/c0585b665e994ac5990b4911b0cc5cfa.json"}}, {"family": "Makaraviciute", "given": "Asta", "initials": "A"}, {"family": "Abdurakhmanov", "given": "Eldar", "initials": "E"}, {"family": "Wermeling", "given": "Fredrik", "initials": "F"}, {"family": "Li", "given": "Shiyu", "initials": "S", "orcid": "0000-0003-4948-8353", "researcher": {"href": "https://publications.scilifelab.se/researcher/eaafe0529dbc46fb904b20cb943dad09.json"}}, {"family": "Danielson", "given": "U Helena", "initials": "UH", "orcid": "0000-0003-2728-0340", "researcher": {"href": "https://publications.scilifelab.se/researcher/b2bf7dffedf44237807c23718c72efa6.json"}}, {"family": "Nyholm", "given": "Leif", "initials": "L", "orcid": "0000-0001-9292-016X", "researcher": {"href": "https://publications.scilifelab.se/researcher/b7be3793cb034f04a7303a3ba8d0d4bf.json"}}, {"family": "Zhang", "given": "Zhen", "initials": "Z", "orcid": "0000-0003-4317-9701", "researcher": {"href": "https://publications.scilifelab.se/researcher/b84c807f13484a2abf4ab92ab77e37ec.json"}}], "type": "journal article", "published": "2020-01-24", "journal": {"title": "ACS Sens.", "issn": "2379-3694", "issn-l": "2379-3694", "volume": "5", "issue": "1", "pages": "217-224"}, "abstract": "As the signals of potentiometric-based DNA ion-selective field effect transistor (ISFET) sensors differ largely from report to report, a systematic revisit to this method is needed. Herein, the hybridization of the target and the probe DNA on the sensor surface and its dependence on the surface probe DNA coverage and the ionic strength were systematically investigated by surface plasmon resonance (SPR). The maximum potentiometric DNA hybridization signal that could be registered by an ISFET sensor was estimated based on the SPR measurements, without considering buffering effects from any side interaction on the sensing electrode. We found that under physiological solutions (200 to 300 mM ionic strength), the ISFET sensor could not register the DNA hybridization events on the sensor surface due to Debye screening. Lowering the salt concentration to enlarge the Debye length would at the same time reduce the surface hybridization efficiency, thus suppressing the signal. This adverse effect of low salt concentration on the hybridization efficiency was also found to be more significant on the surface with higher probe coverage due to steric hindrance. With the method of diluting buffer, the maximum potentiometric signal generated by the DNA hybridization was estimated to be only around 120 mV with the lowest detection limit of 30 nM, occurring on a surface with optimized probe coverage and in the tris buffer with 10 mM NaCl. An alternative method would be to achieve high-efficiency hybridization in the buffer with high salt concentration (1 M NaCl) and then to perform potentiometric measurements in the buffer with low salt concentration (1 mM NaCl). Based on the characterization of the stability of the hybridized DNA duplexes on the sensor surface in low salt concentration buffer solutions, the estimated maximum potentiometric signal could be significantly higher using the alternative method. The lowest detection limit for this alternative method was estimated to be around 0.6 nM. This work can serve as an important quantitative reference for potentiometric DNA sensors.", "doi": "10.1021/acssensors.9b02086", "pmid": "31833355", "labels": {"Drug Discovery and Development": "Technology development"}, "xrefs": [], "notes": [], "created": "2020-01-07T13:59:48.906Z", "modified": "2025-10-17T13:05:08.079Z"}, {"entity": "publication", "iuid": "ab3cc4d0906f402b8e0f5a5fecb6f0a0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ab3cc4d0906f402b8e0f5a5fecb6f0a0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ab3cc4d0906f402b8e0f5a5fecb6f0a0"}}, "title": "CREBBP and WDR 24 Identified as Candidate Genes for Quantitative Variation in Red-Brown Plumage Colouration in the Chicken.", "authors": [{"family": "Fogelholm", "given": "J", "initials": "J"}, {"family": "Henriksen", "given": "R", "initials": "R"}, {"family": "H\u00f6glund", "given": "A", "initials": "A"}, {"family": "Huq", "given": "N", "initials": "N"}, {"family": "Johnsson", "given": "M", "initials": "M"}, {"family": "Lenz", "given": "R", "initials": "R"}, {"family": "Jensen", "given": "P", "initials": "P"}, {"family": "Wright", "given": "D", "initials": "D"}], "type": "journal article", "published": "2020-01-24", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "1161", "issn-l": "2045-2322"}, "abstract": "Plumage colouration in birds is important for a plethora of reasons, ranging from camouflage, sexual signalling, and species recognition. The genes underlying colour variation have been vital in understanding how genes can affect a phenotype. Multiple genes have been identified that affect plumage variation, but research has principally focused on major-effect genes (such as those causing albinism, barring, and the like), rather than the smaller effect modifier loci that more subtly influence colour. By utilising a domestic \u00d7 wild advanced intercross with a combination of classical QTL mapping of red colouration as a quantitative trait and a targeted genetical genomics approach, we have identified five separate candidate genes (CREBBP, WDR24, ARL8A, PHLDA3, LAD1) that putatively influence quantitative variation in red-brown colouration in chickens. By treating colour as a quantitative rather than qualitative trait, we have identified both QTL and genes of small effect. Such small effect loci are potentially far more prevalent in wild populations, and can therefore potentially be highly relevant to colour evolution.", "doi": "10.1038/s41598-020-57710-7", "pmid": "31980681", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-57710-7"}, {"db": "pmc", "key": "PMC6981141"}], "notes": [], "created": "2020-02-04T11:55:41.471Z", "modified": "2024-01-16T13:48:43.050Z"}, {"entity": "publication", "iuid": "be7a47db1e114288bbb480454a47fab5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/be7a47db1e114288bbb480454a47fab5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/be7a47db1e114288bbb480454a47fab5"}}, "title": "The Medical Genome Reference Bank contains whole genome and phenotype data of 2570 healthy elderly.", "authors": [{"family": "Pinese", "given": "Mark", "initials": "M"}, {"family": "Lacaze", "given": "Paul", "initials": "P", "orcid": "0000-0002-0902-6798", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe2ef319274d47af81a415d276772fd2.json"}}, {"family": "Rath", "given": "Emma M", "initials": "EM", "orcid": "0000-0002-8430-5236", "researcher": {"href": "https://publications.scilifelab.se/researcher/cbb64814760845e898ad26b3f5bd3631.json"}}, {"family": "Stone", "given": "Andrew", "initials": "A"}, {"family": "Brion", "given": "Marie-Jo", "initials": "MJ"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Nagpal", "given": "Sini", "initials": "S"}, {"family": "Puttick", "given": "Clare", "initials": "C"}, {"family": "Husson", "given": "Shane", "initials": "S"}, {"family": "Degrave", "given": "Dmitry", "initials": "D"}, {"family": "Cristina", "given": "Tina Navin", "initials": "TN"}, {"family": "Kahl", "given": "Vivian F S", "initials": "VFS"}, {"family": "Statham", "given": "Aaron L", "initials": "AL"}, {"family": "Woods", "given": "Robyn L", "initials": "RL"}, {"family": "McNeil", "given": "John J", "initials": "JJ", "orcid": "0000-0002-1049-5129", "researcher": {"href": "https://publications.scilifelab.se/researcher/2f523d0ed8654c6cad196a4a30273dc1.json"}}, {"family": "Riaz", "given": "Moeen", "initials": "M"}, {"family": "Barr", "given": "Margo", "initials": "M"}, {"family": "Nelson", "given": "Mark R", "initials": "MR"}, {"family": "Reid", "given": "Christopher M", "initials": "CM"}, {"family": "Murray", "given": "Anne M", "initials": "AM"}, {"family": "Shah", "given": "Raj C", "initials": "RC"}, {"family": "Wolfe", "given": "Rory", "initials": "R"}, {"family": "Atkins", "given": "Joshua R", "initials": "JR", "orcid": "0000-0003-0821-1112", "researcher": {"href": "https://publications.scilifelab.se/researcher/d5c3c3b5566f4189893fc6f9b59bd639.json"}}, {"family": "Fitzsimmons", "given": "Chantel", "initials": "C"}, {"family": "Cairns", "given": "Heath M", "initials": "HM"}, {"family": "Green", "given": "Melissa J", "initials": "MJ"}, {"family": "Carr", "given": "Vaughan J", "initials": "VJ"}, {"family": "Cowley", "given": "Mark J", "initials": "MJ"}, {"family": "Pickett", "given": "Hilda A", "initials": "HA"}, {"family": "James", "given": "Paul A", "initials": "PA", "orcid": "0000-0002-4361-4657", "researcher": {"href": "https://publications.scilifelab.se/researcher/441138eb23d04342bca5e835815f5a79.json"}}, {"family": "Powell", "given": "Joseph E", "initials": "JE"}, {"family": "Kaplan", "given": "Warren", "initials": "W"}, {"family": "Gibson", "given": "Greg", "initials": "G", "orcid": "0000-0002-5352-5877", "researcher": {"href": "https://publications.scilifelab.se/researcher/4a4cf08629614ba3986edd2971a28848.json"}}, {"family": "Gyllensten", "given": "Ulf", "initials": "U"}, {"family": "Cairns", "given": "Murray J", "initials": "MJ", "orcid": "0000-0003-2490-2538", "researcher": {"href": "https://publications.scilifelab.se/researcher/45db703eb69a49c390ce333c778617fa.json"}}, {"family": "McNamara", "given": "Martin", "initials": "M"}, {"family": "Dinger", "given": "Marcel E", "initials": "ME", "orcid": "0000-0003-4423-934X", "researcher": {"href": "https://publications.scilifelab.se/researcher/5451fbf330bf4a5e9cfe17b9a66d5bd7.json"}}, {"family": "Thomas", "given": "David M", "initials": "DM", "orcid": "0000-0002-2527-5428", "researcher": {"href": "https://publications.scilifelab.se/researcher/a5d3768414324650b161ccbb0de36a00.json"}}], "type": "journal article", "published": "2020-01-23", "journal": {"volume": "11", "issn": "2041-1723", "issue": "1", "pages": "435", "title": "Nat Commun", "issn-l": "2041-1723"}, "abstract": "Population health research is increasingly focused on the genetic determinants of healthy ageing, but there is no public resource of whole genome sequences and phenotype data from healthy elderly individuals. Here we describe the first release of the Medical Genome Reference Bank (MGRB), comprising whole genome sequence and phenotype of 2570 elderly Australians depleted for cancer, cardiovascular disease, and dementia. We analyse the MGRB for single-nucleotide, indel and structural variation in the nuclear and mitochondrial genomes. MGRB individuals have fewer disease-associated common and rare germline variants, relative to both cancer cases and the gnomAD and UK Biobank cohorts, consistent with risk depletion. Age-related somatic changes are correlated with grip strength in men, suggesting blood-derived whole genomes may also provide a biologic measure of age-related functional deterioration. The MGRB provides a broadly applicable reference cohort for clinical genetics and genomic association studies, and for understanding the genetics of healthy ageing.", "doi": "10.1038/s41467-019-14079-0", "pmid": "31974348", "labels": {"National Genomics Infrastructure": "Collaborative", "NGI Uppsala (Uppsala Genome Center)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-019-14079-0"}, {"db": "pmc", "key": "PMC6978518"}], "notes": [], "created": "2020-02-11T10:08:40.950Z", "modified": "2021-11-10T12:54:41.902Z"}, {"entity": "publication", "iuid": "a0852875f0e24bf78b3c291325fc9de9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a0852875f0e24bf78b3c291325fc9de9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a0852875f0e24bf78b3c291325fc9de9"}}, "title": "Reverse engineering directed gene regulatory networks from transcriptomics and proteomics data of biomining bacterial communities with approximate Bayesian computation and steady-state signalling simulations.", "authors": [{"family": "Buetti-Dinh", "given": "Antoine", "initials": "A", "orcid": "0000-0002-6469-0296", "researcher": {"href": "https://publications.scilifelab.se/researcher/071a99356d6f4650a6707dc84777a66c.json"}}, {"family": "Herold", "given": "Malte", "initials": "M", "orcid": "0000-0003-2627-0159", "researcher": {"href": "https://publications.scilifelab.se/researcher/70759c28794141fbb123901947534ec4.json"}}, {"family": "Christel", "given": "Stephan", "initials": "S", "orcid": "0000-0003-0021-2452", "researcher": {"href": "https://publications.scilifelab.se/researcher/9db0f79d5ee144308ccb724e51959bc8.json"}}, {"family": "El Hajjami", "given": "Mohamed", "initials": "M"}, {"family": "Delogu", "given": "Francesco", "initials": "F"}, {"family": "Ilie", "given": "Olga", "initials": "O"}, {"family": "Bellenberg", "given": "S\u00f6ren", "initials": "S"}, {"family": "Wilmes", "given": "Paul", "initials": "P", "orcid": "0000-0002-6478-2924", "researcher": {"href": "https://publications.scilifelab.se/researcher/a0fa4b91d7384fda991fcda7c3df41be.json"}}, {"family": "Poetsch", "given": "Ansgar", "initials": "A"}, {"family": "Sand", "given": "Wolfgang", "initials": "W"}, {"family": "Vera", "given": "Mario", "initials": "M", "orcid": "0000-0002-1762-4421", "researcher": {"href": "https://publications.scilifelab.se/researcher/2a9ade6aac4e45399d1e1207a8b58398.json"}}, {"family": "Pivkin", "given": "Igor V", "initials": "IV"}, {"family": "Friedman", "given": "Ran", "initials": "R", "orcid": "0000-0001-8696-3104", "researcher": {"href": "https://publications.scilifelab.se/researcher/aff68ae331c349e189a6ecf511823fc3.json"}}, {"family": "Dopson", "given": "Mark", "initials": "M", "orcid": "0000-0002-9622-3318", "researcher": {"href": "https://publications.scilifelab.se/researcher/1dc9cc6dadf6483e88d855dc78709a59.json"}}], "type": "journal article", "published": "2020-01-21", "journal": {"title": "BMC Bioinformatics", "issn": "1471-2105", "volume": "21", "issue": "1", "pages": "23", "issn-l": "1471-2105"}, "abstract": "Network inference is an important aim of systems biology. It enables the transformation of OMICs datasets into biological knowledge. It consists of reverse engineering gene regulatory networks from OMICs data, such as RNAseq or mass spectrometry-based proteomics data, through computational methods. This approach allows to identify signalling pathways involved in specific biological functions. The ability to infer causality in gene regulatory networks, in addition to correlation, is crucial for several modelling approaches and allows targeted control in biotechnology applications.\n\nWe performed simulations according to the approximate Bayesian computation method, where the core model consisted of a steady-state simulation algorithm used to study gene regulatory networks in systems for which a limited level of details is available. The simulations outcome was compared to experimentally measured transcriptomics and proteomics data through approximate Bayesian computation.\n\nThe structure of small gene regulatory networks responsible for the regulation of biological functions involved in biomining were inferred from multi OMICs data of mixed bacterial cultures. Several causal inter- and intraspecies interactions were inferred between genes coding for proteins involved in the biomining process, such as heavy metal transport, DNA damage, replication and repair, and membrane biogenesis. The method also provided indications for the role of several uncharacterized proteins by the inferred connection in their network context.\n\nThe combination of fast algorithms with high-performance computing allowed the simulation of a multitude of gene regulatory networks and their comparison to experimentally measured OMICs data through approximate Bayesian computation, enabling the probabilistic inference of causality in gene regulatory networks of a multispecies bacterial system involved in biomining without need of single-cell or multiple perturbation experiments. This information can be used to influence biological functions and control specific processes in biotechnology applications.", "doi": "10.1186/s12859-019-3337-9", "pmid": "31964336", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12859-019-3337-9"}, {"db": "pmc", "key": "PMC6975020"}], "notes": [], "created": "2020-07-08T13:03:37.375Z", "modified": "2024-01-16T13:48:43.057Z"}, {"entity": "publication", "iuid": "c99b57cb90664ceca649183724112a64", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c99b57cb90664ceca649183724112a64.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c99b57cb90664ceca649183724112a64"}}, "title": "Modulation of Structural Heterogeneity Controls Phytochrome Photoswitching.", "authors": [{"family": "Gustavsson", "given": "Emil", "initials": "E", "orcid": "0000-0003-0166-1786", "researcher": {"href": "https://publications.scilifelab.se/researcher/474b967a7726414288142c12b7b9dc3f.json"}}, {"family": "Isaksson", "given": "Linn\u00e9a", "initials": "L"}, {"family": "Persson", "given": "Cecilia", "initials": "C", "orcid": "0000-0001-6663-6536", "researcher": {"href": "https://publications.scilifelab.se/researcher/5fb6fe3555374aec90b2a8b9dfd8016b.json"}}, {"family": "Mayzel", "given": "Maxim", "initials": "M"}, {"family": "Brath", "given": "Ulrika", "initials": "U"}, {"family": "Vrhovac", "given": "Lidija", "initials": "L"}, {"family": "Ihalainen", "given": "Janne A", "initials": "JA"}, {"family": "Karlsson", "given": "B G\u00f6ran", "initials": "BG"}, {"family": "Orekhov", "given": "Vladislav", "initials": "V"}, {"family": "Westenhoff", "given": "Sebastian", "initials": "S"}], "type": "journal article", "published": "2020-01-21", "journal": {"title": "Biophysical Journal", "issn": "1542-0086", "volume": "118", "issue": "2", "pages": "415-421", "issn-l": "0006-3495"}, "abstract": "Phytochromes sense red/far-red light and control many biological processes in plants, fungi, and bacteria. Although the crystal structures of dark- and light-adapted states have been determined, the molecular mechanisms underlying photoactivation remain elusive. Here, we demonstrate that the conserved tongue region of the PHY domain of a 57-kDa photosensory module of Deinococcus radiodurans phytochrome changes from a structurally heterogeneous dark state to an ordered, light-activated state. The results were obtained in solution by utilizing a laser-triggered activation approach detected on the atomic level with high-resolution protein NMR spectroscopy. The data suggest that photosignaling of phytochromes relies on careful modulation of structural heterogeneity of the PHY tongue.", "doi": "10.1016/j.bpj.2019.11.025", "pmid": "31839260", "labels": {"Swedish NMR Centre": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0006-3495(19)30948-8"}, {"db": "pmc", "key": "PMC6976809"}], "notes": [], "created": "2020-01-07T11:42:31.260Z", "modified": "2025-10-17T13:03:57.202Z"}, {"entity": "publication", "iuid": "8e7d434d65094896b5c0c4f4328ae62e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8e7d434d65094896b5c0c4f4328ae62e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8e7d434d65094896b5c0c4f4328ae62e"}}, "title": "Transcriptome analysis of fibroblasts from schizophrenia patients reveals differential expression of schizophrenia-related genes.", "authors": [{"family": "Etemadikhah", "given": "Mitra", "initials": "M", "orcid": "0000-0001-5795-9085", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e68ca63254a4b5697188bb87087852f.json"}}, {"family": "Niazi", "given": "Adnan", "initials": "A", "orcid": "0000-0003-0311-5279", "researcher": {"href": "https://publications.scilifelab.se/researcher/c9e07c9891804a60980eb07956a7cd0d.json"}}, {"family": "Wetterberg", "given": "Lennart", "initials": "L"}, {"family": "Feuk", "given": "Lars", "initials": "L", "orcid": "0000-0003-2355-2919", "researcher": {"href": "https://publications.scilifelab.se/researcher/3eb2f826b3554d4b9971bf0766b275c4.json"}}], "type": "journal article", "published": "2020-01-20", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "630", "issn-l": "2045-2322"}, "abstract": "Schizophrenia is a complex neurodevelopmental disorder with high rate of morbidity and mortality. While the heritability rate is high, the precise etiology is still unknown. Although schizophrenia is a central nervous system disorder, studies using peripheral tissues have also been established to search for patient specific biomarkers and to increase understanding of schizophrenia etiology. Among all peripheral tissues, fibroblasts stand out as they are easy to obtain and culture. Furthermore, they keep genetic stability for long period and exhibit molecular similarities to cells from nervous system. Using a unique set of fibroblast samples from a genetically isolated population in northern Sweden, we performed whole transcriptome sequencing to compare differentially expressed genes in seven controls and nine patients. We found differential fibroblast expression between cases and controls for 48 genes, including eight genes previously implicated in schizophrenia or schizophrenia related pathways; HGF, PRRT2, EGR1, EGR3, C11orf87, TLR3, PLEKHH2 and PIK3CD. Weighted gene correlation network analysis identified three differentially co-expressed networks of genes significantly-associated with schizophrenia. All three modules were significantly suppressed in patients compared to control, with one module highly enriched in genes involved in synaptic plasticity, behavior and synaptic transmission. In conclusion, our results support the use of fibroblasts for identification of differentially expressed genes in schizophrenia and highlight dysregulation of synaptic networks as an important mechanism in schizophrenia.", "doi": "10.1038/s41598-020-57467-z", "pmid": "31959813", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-020-57467-z"}, {"db": "pmc", "key": "PMC6971273"}], "notes": [], "created": "2020-07-03T05:23:47.172Z", "modified": "2024-01-16T13:48:43.065Z"}, {"entity": "publication", "iuid": "0e32c4bba4b54a9d966c5a19ca859cac", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0e32c4bba4b54a9d966c5a19ca859cac.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0e32c4bba4b54a9d966c5a19ca859cac"}}, "title": "Loss of centromere function drives karyotype evolution in closely related Malassezia species.", "authors": [{"family": "Sankaranarayanan", "given": "Sundar Ram", "initials": "SR"}, {"family": "Ianiri", "given": "Giuseppe", "initials": "G", "orcid": "0000-0002-3278-8678", "researcher": {"href": "https://publications.scilifelab.se/researcher/c5b13626c7d0458f92a3319cfc9a3c33.json"}}, {"family": "Coelho", "given": "Marco A", "initials": "MA"}, {"family": "Reza", "given": "Md Hashim", "initials": "MH"}, {"family": "Thimmappa", "given": "Bhagya C", "initials": "BC"}, {"family": "Ganguly", "given": "Promit", "initials": "P"}, {"family": "Vadnala", "given": "Rakesh Netha", "initials": "RN"}, {"family": "Sun", "given": "Sheng", "initials": "S"}, {"family": "Siddharthan", "given": "Rahul", "initials": "R", "orcid": "0000-0002-2233-0954", "researcher": {"href": "https://publications.scilifelab.se/researcher/cbf80a9f0f79447e991ca439c69e0b96.json"}}, {"family": "Tellgren-Roth", "given": "Christian", "initials": "C"}, {"family": "Dawson", "given": "Thomas L", "initials": "TL"}, {"family": "Heitman", "given": "Joseph", "initials": "J"}, {"family": "Sanyal", "given": "Kaustuv", "initials": "K", "orcid": "0000-0002-6611-4073", "researcher": {"href": "https://publications.scilifelab.se/researcher/d8ef4495196c4f489391e25206b20931.json"}}], "type": "journal article", "published": "2020-01-20", "journal": {"title": "Elife", "issn": "2050-084X", "volume": "9", "issue": null, "issn-l": "2050-084X"}, "abstract": "Genomic rearrangements associated with speciation often result in variation in chromosome number among closely related species. Malassezia species show variable karyotypes ranging between six and nine chromosomes. Here, we experimentally identified all eight centromeres in M. sympodialis as 3-5-kb long kinetochore-bound regions that span an AT-rich core and are depleted of the canonical histone H3. Centromeres of similar sequence features were identified as CENP-A-rich regions in Malassezia furfur, which has seven chromosomes, and histone H3 depleted regions in Malassezia slooffiae and Malassezia globosa with nine chromosomes each. Analysis of synteny conservation across centromeres with newly generated chromosome-level genome assemblies suggests two distinct mechanisms of chromosome number reduction from an inferred nine-chromosome ancestral state: (a) chromosome breakage followed by loss of centromere DNA and (b) centromere inactivation accompanied by changes in DNA sequence following chromosome-chromosome fusion. We propose that AT-rich centromeres drive karyotype diversity in the Malassezia species complex through breakage and inactivation.", "doi": "10.7554/eLife.53944", "pmid": "31958060", "labels": {"National Genomics Infrastructure": "Collaborative", "NGI Uppsala (Uppsala Genome Center)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "53944"}, {"db": "pmc", "key": "PMC7025860"}], "notes": [], "created": "2020-02-11T18:53:04.725Z", "modified": "2021-11-10T12:54:46.684Z"}, {"entity": "publication", "iuid": "3d7ec0e48ab24238af7a2a594034049a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3d7ec0e48ab24238af7a2a594034049a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3d7ec0e48ab24238af7a2a594034049a"}}, "title": "Genome-Based Comparison of All Species of the Genus Moorella, and Status of the Species Moorella thermoacetica and Moorella thermoautotrophica.", "authors": [{"family": "Redl", "given": "Stephanie", "initials": "S"}, {"family": "Poehlein", "given": "Anja", "initials": "A"}, {"family": "Esser", "given": "Carola", "initials": "C"}, {"family": "Bengelsdorf", "given": "Frank R", "initials": "FR"}, {"family": "Jensen", "given": "Torbj\u00f8rn \u00d8", "initials": "T\u00d8"}, {"family": "Jendresen", "given": "Christian B", "initials": "CB"}, {"family": "Tindall", "given": "Brian J", "initials": "BJ"}, {"family": "Daniel", "given": "Rolf", "initials": "R"}, {"family": "D\u00fcrre", "given": "Peter", "initials": "P"}, {"family": "Nielsen", "given": "Alex T", "initials": "AT"}], "type": "journal article", "published": "2020-01-17", "journal": {"title": "Front Microbiol", "issn": "1664-302X", "volume": "10", "issue": null, "pages": "3070", "issn-l": "1664-302X"}, "abstract": "Fermentation of gases provides a promising opportunity for the production of biochemicals from renewable resources, which has resulted in a growing interest in acetogenic bacteria. Thermophilic organisms provide potential advantages for the fermentation of, e.g., syngas into for example volatile compounds, and the thermophiles Moorella thermoacetica and Moorella thermoautotrophica have become model organisms of acetogenic metabolism. The justification for the recognition of the closely related species M. thermoautotrophica has, however, recently been disputed. In order to expand knowledge on the genus, we have here genome sequenced a total of 12 different M. thermoacetica and M. thermoautotrophica strains. From the sequencing results, it became clear that M. thermoautotrophica DSM 1974T consists of at least two different strains. Two different strains were isolated in Lyngby and Ulm from a DSM 1974T culture obtained from the DSMZ (Leibniz-Institut DSMZ-Deutsche Sammlung von Mikroorganismen und Zellkulturen GmbH, Brunswick, Germany). Phylogenetic analysis revealed a close relationship between all the sequenced genomes, suggesting that the two strains detected in the type strain of the species M. thermoautotrophica could not be distinguished at the species level from M. thermoacetica. Despite genetic similarities, differences in genomic features were observed between the strains. Differences in compounds that can serve as carbon and energy sources for selected strains were also identified. On the contrary, strain DSM 21394, currently still named M. thermoacetica, obviously represents a new Moorella species. In addition, based on genome analysis and comparison M. glycerini NMP, M. stamsii DSM 26217T, and M. perchloratireducens An10 cannot be distinguished at the species level. Thus, this comprehensive analysis provides a significantly increased knowledge of the genetic diversity of Moorella strains.", "doi": "10.3389/fmicb.2019.03070", "pmid": "32010113", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC6978639"}], "notes": [], "created": "2020-03-24T07:53:18.355Z", "modified": "2021-11-10T12:54:48.926Z"}, {"entity": "publication", "iuid": "798d0c199a87482abd2a408a2148a1ac", "links": {"self": {"href": "https://publications.scilifelab.se/publication/798d0c199a87482abd2a408a2148a1ac.json"}, "display": {"href": "https://publications.scilifelab.se/publication/798d0c199a87482abd2a408a2148a1ac"}}, "title": "A spontaneous mitonuclear epistasis converging on Rieske Fe-S protein exacerbates complex III deficiency in mice.", "authors": [{"family": "Purhonen", "given": "Janne", "initials": "J"}, {"family": "Grigorjev", "given": "Vladislav", "initials": "V"}, {"family": "Ekiert", "given": "Robert", "initials": "R", "orcid": "0000-0002-8879-0646", "researcher": {"href": "https://publications.scilifelab.se/researcher/18f5478e3272434f8e04014a4da545b5.json"}}, {"family": "Aho", "given": "Noora", "initials": "N"}, {"family": "Rajendran", "given": "Jayasimman", "initials": "J", "orcid": "0000-0003-3487-8260", "researcher": {"href": "https://publications.scilifelab.se/researcher/92dfb99f063c475086ad84783ab34716.json"}}, {"family": "Pietras", "given": "Rafa\u0142", "initials": "R", "orcid": "0000-0001-8424-6590", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f9c7e05c9284550ad49f0cc9237ad45.json"}}, {"family": "Truv\u00e9", "given": "Katarina", "initials": "K", "orcid": "0000-0002-2449-8283", "researcher": {"href": "https://publications.scilifelab.se/researcher/0c36d2ff5111435aa23416cdfc359b2d.json"}}, {"family": "Wikstr\u00f6m", "given": "M\u00e5rten", "initials": "M", "orcid": "0000-0002-7527-4415", "researcher": {"href": "https://publications.scilifelab.se/researcher/66d471fc1c914756ac37da41bb759da4.json"}}, {"family": "Sharma", "given": "Vivek", "initials": "V"}, {"family": "Osyczka", "given": "Artur", "initials": "A"}, {"family": "Fellman", "given": "Vineta", "initials": "V", "orcid": "0000-0002-1355-5633", "researcher": {"href": "https://publications.scilifelab.se/researcher/3c2179b7025441f688426ab24abd390e.json"}}, {"family": "Kallij\u00e4rvi", "given": "Jukka", "initials": "J", "orcid": "0000-0003-3773-7025", "researcher": {"href": "https://publications.scilifelab.se/researcher/c592c2565d4f42efb54b3e6016968ddf.json"}}], "type": "journal article", "published": "2020-01-16", "journal": {"volume": "11", "issn": "2041-1723", "issue": "1", "pages": "322", "title": "Nat Commun", "issn-l": "2041-1723"}, "abstract": "We previously observed an unexpected fivefold (35 vs. 200 days) difference in the survival of respiratory chain complex III (CIII) deficient Bcs1lp.S78G mice between two congenic backgrounds. Here, we identify a spontaneous homoplasmic mtDNA variant (m.G14904A, mt-Cybp.D254N), affecting the CIII subunit cytochrome b (MT-CYB), in the background with short survival. We utilize maternal inheritance of mtDNA to confirm this as the causative variant and show that it further decreases the low CIII activity in Bcs1lp.S78G tissues to below survival threshold by 35 days of age. Molecular dynamics simulations predict D254N to restrict the flexibility of MT-CYB ef loop, potentially affecting RISP dynamics. In Rhodobacter cytochrome bc1 complex the equivalent substitution causes a kinetics defect with longer occupancy of RISP head domain towards the quinol oxidation site. These findings represent a unique case of spontaneous mitonuclear epistasis and highlight the role of mtDNA variation as modifier of mitochondrial disease phenotypes.", "doi": "10.1038/s41467-019-14201-2", "pmid": "31949167", "labels": {"National Genomics Infrastructure": "Service", "Bioinformatics Support, Infrastructure and Training": "Service", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support and Infrastructure": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-019-14201-2"}, {"db": "pmc", "key": "PMC6965120"}], "notes": [], "created": "2020-02-03T09:00:33.293Z", "modified": "2021-11-10T12:44:51.374Z"}, {"entity": "publication", "iuid": "c982efa83ad042baaaa633f71d3b3cb9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c982efa83ad042baaaa633f71d3b3cb9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c982efa83ad042baaaa633f71d3b3cb9"}}, "title": "Gene regulatory response to hyposalinity in the brown seaweed Fucus vesiculosus.", "authors": [{"family": "Rugiu", "given": "Luca", "initials": "L", "orcid": "0000-0002-9675-7168", "researcher": {"href": "https://publications.scilifelab.se/researcher/8d411b99abcc4474aff904e43247fb7a.json"}}, {"family": "Panova", "given": "Marina", "initials": "M"}, {"family": "Pereyra", "given": "Ricardo Tom\u00e1s", "initials": "RT"}, {"family": "Jormalainen", "given": "Veijo", "initials": "V"}], "type": "journal article", "published": "2020-01-13", "journal": {"title": "BMC Genomics", "issn": "1471-2164", "volume": "21", "issue": "1", "pages": "42", "issn-l": "1471-2164"}, "abstract": "Rockweeds are among the most important foundation species of temperate rocky littoral shores. In the Baltic Sea, the rockweed Fucus vesiculosus is distributed along a decreasing salinity gradient from the North Atlantic entrance to the low-salinity regions in the north-eastern margins, thus, demonstrating a remarkable tolerance to hyposalinity. The underlying mechanisms for this tolerance are still poorly understood. Here, we exposed F. vesiculosus from two range-margin populations to the hyposaline (2.5 PSU - practical salinity unit) conditions that are projected to occur in the region by the end of this century as a result of climate change. We used transcriptome analysis (RNA-seq) to determine the gene expression patterns associated with hyposalinity acclimation, and examined the variation in these patterns between the sampled populations.\n\nHyposalinity induced different responses in the two populations: in one, only 26 genes were differentially expressed between salinity treatments, while the other population demonstrated up- or downregulation in 3072 genes. In the latter population, the projected future hyposalinity induced an acute response in terms of antioxidant production. Genes associated with membrane composition and structure were also heavily involved, with the upregulation of fatty acid and actin production, and the downregulation of ion channels and alginate pathways. Changes in gene expression patterns clearly indicated an inhibition of the photosynthetic machinery, with a consequent downregulation of carbohydrate production. Simultaneously, energy consumption increased, as revealed by the upregulation of genes associated with respiration and ATP synthesis. Overall, the genes that demonstrated the largest increase in expression were ribosomal proteins involved in translation pathways. The fixation rate of SNP:s was higher within genes responding to hyposalinity than elsewhere in the transcriptome.\n\nThe high fixation rate in the genes coding for salinity acclimation mechanisms implies strong selection for them. The among-population differentiation that we observed in the transcriptomic response to hyposalinity stress suggests that populations of F. vesiculosus may differ in their tolerance to future desalination, possibly as a result of local adaptation to salinity conditions within the Baltic Sea. These results emphasise the importance of considering interspecific genetic variation when evaluating the consequences of environmental change.", "doi": "10.1186/s12864-020-6470-y", "pmid": "31931708", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12864-020-6470-y"}, {"db": "pmc", "key": "PMC6958763"}], "notes": [], "created": "2020-07-08T13:03:42.198Z", "modified": "2024-01-16T13:48:43.072Z"}, {"entity": "publication", "iuid": "cae2c19d93fe471eac4b766e6643b20a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cae2c19d93fe471eac4b766e6643b20a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cae2c19d93fe471eac4b766e6643b20a"}}, "title": "Development and characterization of an EMS-mutagenized wheat population and identification of salt-tolerant wheat lines.", "authors": [{"family": "Lethin", "given": "Johanna", "initials": "J"}, {"family": "Shakil", "given": "Shahriar S M", "initials": "SSM"}, {"family": "Hassan", "given": "Sameer", "initials": "S"}, {"family": "Sirijovski", "given": "Nick", "initials": "N"}, {"family": "T\u00f6pel", "given": "Mats", "initials": "M"}, {"family": "Olsson", "given": "Olof", "initials": "O"}, {"family": "Aronsson", "given": "Henrik", "initials": "H", "orcid": "0000-0003-4424-8481", "researcher": {"href": "https://publications.scilifelab.se/researcher/0227592dd1174af4a8a8dc39183b0f19.json"}}], "type": "journal article", "published": "2020-01-13", "journal": {"title": "BMC Plant Biol.", "issn": "1471-2229", "volume": "20", "issue": "1", "pages": "18", "issn-l": "1471-2229"}, "abstract": "Triticum aestivum (wheat) is one of the world's oldest crops and has been used for >8000 years as a food crop in North Africa, West Asia and Europe. Today, wheat is one of the most important sources of grain for humans, and is cultivated on greater areas of land than any other crop. As the human population increases and soil salinity becomes more prevalent, there is increased pressure on wheat breeders to develop salt-tolerant varieties in order to meet growing demands for yield and grain quality. Here we developed a mutant wheat population using the moderately salt-tolerant Bangladeshi variety BARI Gom-25, with the primary goal of further increasing salt tolerance.\n\nAfter titrating the optimal ethyl methanesulfonate (EMS) concentration, ca 30,000 seeds were treated with 1% EMS, and 1676 lines, all originating from single seeds, survived through the first four generations. Most mutagenized lines showed a similar phenotype to BARI Gom-25, although visual differences such as dwarfing, giant plants, early and late flowering and altered leaf morphology were seen in some lines. By developing an assay for salt tolerance, and by screening the mutagenized population, we identified 70 lines exhibiting increased salt tolerance. The selected lines typically showed a 70% germination rate on filter paper soaked in 200 mM NaCl, compared to 0-30% for BARI Gom-25. From two of the salt-tolerant OlsAro lines (OA42 and OA70), genomic DNA was sequenced to 15x times coverage. A comparative analysis against the BARI Gom-25 genomic sequence identified a total of 683,201 (OA42), and 768,954 (OA70) SNPs distributed throughout the three sub-genomes (A, B and D). The mutation frequency was determined to be approximately one per 20,000 bp. All the 70 selected salt-tolerant lines were tested for root growth in the laboratory, and under saline field conditions in Bangladesh. The results showed that all the lines selected for tolerance showed a better salt tolerance phenotype than both BARI Gom-25 and other local wheat varieties tested.\n\nThe mutant wheat population developed here will be a valuable resource in the development of novel salt-tolerant varieties for the benefit of saline farming.", "doi": "10.1186/s12870-019-2137-8", "pmid": "31931695", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12870-019-2137-8"}, {"db": "pmc", "key": "PMC6958588"}], "notes": [], "created": "2020-07-08T13:03:36.627Z", "modified": "2024-01-16T13:48:43.079Z"}, {"entity": "publication", "iuid": "2d6fcf51b59f4fb5899c7939ea779473", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2d6fcf51b59f4fb5899c7939ea779473.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2d6fcf51b59f4fb5899c7939ea779473"}}, "title": "Screening for bioactive secondary metabolites in Sri Lankan medicinal plants by microfractionation and targeted isolation of antimicrobial flavonoids from Derris scandens.", "authors": [{"family": "Mohotti", "given": "Supun", "initials": "S"}, {"family": "Rajendran", "given": "Sanjeevan", "initials": "S"}, {"family": "Muhammad", "given": "Taj", "initials": "T"}, {"family": "Str\u00f6mstedt", "given": "Adam A", "initials": "AA"}, {"family": "Adhikari", "given": "Achyut", "initials": "A"}, {"family": "Burman", "given": "Robert", "initials": "R"}, {"family": "de Silva", "given": "E D", "initials": "ED"}, {"family": "G\u00f6ransson", "given": "Ulf", "initials": "U"}, {"family": "Hettiarachchi", "given": "C M", "initials": "CM"}, {"family": "Gunasekera", "given": "Sunithi", "initials": "S"}], "type": "journal article", "published": "2020-01-10", "journal": {"title": "Journal of Ethnopharmacology", "issn": "1872-7573", "volume": "246", "issue": null, "pages": "112158", "issn-l": "0378-8741"}, "abstract": "Sri Lanka is known to have very diverse flora. Many of these species are used for plant-based remedies, which form the integral part of two Sri Lankan systems of traditional medicine, Ayurveda and Deshiya Chikitsa. Despite their widespread use, only a limited number of studies have probed into the scientific evidence for bioactivity of these medicinal plants. Such studies rarely progress to the identification of bioactive natural products.\n\nThe primary aim was to develop a bioactivity screening method and apply it to 50 Sri Lankan medicinal plants where antimicrobial properties could be relevant for its traditional use. The subsequent aim was the progression into defining and characterising potent isolates within targeted compound classes from such plants, i.e. Derris scandens and its antimicrobial flavonoids.\n\nThe plant collection comprised 24 species of Fabaceae, 15 Rubiaceae, 7 Solanaceae and 4 Cucurbitaceae plants. These 50 species were collected based on their ethnopharmacological importance and use in Sri Lankan traditional medicine. Crude extracts from each species were initially subjected to radial disc diffusion and microdilution assays. Subsequently, aqueous extracts of all plants were microfractionated in deep well plates using reversed-phase HPLC. Fractions were tested for antibacterial and cytotoxic activities and masses of target bioactive compounds were identified using mass spectrometry. Bioactive compounds with the masses identified through microfractions were isolated from Derris scandens using reversed-phase HPLC. The isolated pure compounds were characterised using LC-MS and NMR.\n\nCrude aqueous extracts from 19 species showed activity against Gram-positive bacteria (Staphylococcus aureus and Bacillus cereus) in the radial disc diffusion assay. Crude aqueous extracts from 34 plant species and organic extracts from 46 plant species were active against S. aureus (\u22644 mg mL-1) in the microdilution assay. Microfractionation demonstrated antibacterial activity for 19 plants and cytotoxicity for 6 plants. Furthermore, target bioactive compounds and their molecular ions were identified during microfractionation. Dalpanitin and vicenin-3, two of the flavonoids isolated from Derris scandens gave MICs of 23 \u03bcg mL-1 against S. aureus. Dalpanitin also exhibited relevant MICs on Gram-negative bacteria (94 \u03bcg mL-1 against Escherichia coli and Pseudomonas aeruginosa).\n\nThe microfractionation protocol developed in this study enabled time-efficient screening of many plants species, using a small quantity of sample material. In addition, microfractionation served as a guiding tool for identifying individual antimicrobial compounds. Through this process, flavonoids were isolated from Derris scandens, out of which dalpanitin and vicenin-3 showed activity in the low micromolar range. The high hit rate for in vitro antibacterial properties from this ethnopharmacologically guided sample collection gives credence to Sri Lankan traditional herbal medicine as a source for drug discovery.", "doi": "10.1016/j.jep.2019.112158", "pmid": "31421182", "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [{"db": "pii", "key": "S0378-8741(19)31623-X"}], "notes": [], "created": "2020-01-09T13:22:08.766Z", "modified": "2025-10-17T13:03:57.230Z"}, {"entity": "publication", "iuid": "be5bf1b1f6ab471bbecf5c58227c4a16", "links": {"self": {"href": "https://publications.scilifelab.se/publication/be5bf1b1f6ab471bbecf5c58227c4a16.json"}, "display": {"href": "https://publications.scilifelab.se/publication/be5bf1b1f6ab471bbecf5c58227c4a16"}}, "title": "A regulatory role for CHD2 in myelopoiesis.", "authors": [{"family": "Shahin Varnoosfaderani", "given": "Farzaneh", "initials": "F"}, {"family": "Palau", "given": "Anna", "initials": "A"}, {"family": "Dong", "given": "Wenbo", "initials": "W", "orcid": "0000-0002-5209-4884", "researcher": {"href": "https://publications.scilifelab.se/researcher/81bd1bba109e48ab9e3c19d3c947bf82.json"}}, {"family": "Persson", "given": "Jenna", "initials": "J"}, {"family": "Durand-Dubief", "given": "Micka\u00ebl", "initials": "M", "orcid": "0000-0002-8556-4459", "researcher": {"href": "https://publications.scilifelab.se/researcher/85c11d5d8d94488aad3e77a84b89ff8d.json"}}, {"family": "Svensson", "given": "J Peter", "initials": "JP", "orcid": "0000-0002-5863-6250", "researcher": {"href": "https://publications.scilifelab.se/researcher/8c226ba652024fdabbbf9203e1edb5d1.json"}}, {"family": "Lennartsson", "given": "Andreas", "initials": "A"}], "type": "journal article", "published": "2020-01-10", "journal": {"title": "Epigenetics", "issn": "1559-2308", "volume": "15", "issue": "6-7", "pages": "702-714", "issn-l": "1559-2294"}, "abstract": "The transcriptional program that dictates haematopoietic cell fate and differentiation requires an epigenetic regulatory and memory function, provided by a network of epigenetic factors that regulate DNA methylation, post-translational histone modifications and chromatin structure. Disturbed epigenetic regulation causes perturbations in the blood cell differentiation program that results in various types of haematopoietic disorders. Thus, accurate epigenetic regulation is essential for functional haematopoiesis. In this study, we used a CRISPR-Cas9 screening approach to identify new epigenetic regulators in myeloid differentiation. We designed a Chromatin-UMI CRISPR guide library targeting 1092 epigenetic regulators. Phorbol 12-myristate 13-acetate (PMA) treatment of the chronic myeloid leukaemia cell line K-562 was used as a megakaryocytic myeloid differentiation model. Both previously described developmental epigenetic regulators and novel factors were identified in our screen. In this study, we validated and characterized a role for the chromatin remodeller CHD2 in myeloid proliferation and megakaryocytic differentiation.", "doi": "10.1080/15592294.2019.1710913", "pmid": "31900031", "labels": {"NGI Stockholm (Genomics Production)": "Service", "NGI Stockholm (Genomics Applications)": "Service", "National Genomics Infrastructure": "Service", "CRISPR Functional Genomics": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7574388"}], "notes": [], "created": "2020-01-20T10:22:28.949Z", "modified": "2024-01-16T13:48:43.086Z"}, {"entity": "publication", "iuid": "7ece5c90f5a84512a7eef65aed76aed2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7ece5c90f5a84512a7eef65aed76aed2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7ece5c90f5a84512a7eef65aed76aed2"}}, "title": "Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure.", "authors": [{"family": "Shah", "given": "Sonia", "initials": "S", "orcid": "0000-0001-5860-4526", "researcher": {"href": "https://publications.scilifelab.se/researcher/c6a8568b3cae476199b27818eeb19e4d.json"}}, {"family": "Henry", "given": "Albert", "initials": "A", "orcid": "0000-0001-7422-2288", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b1557b87fc542eb8e4d7b733e5b79dc.json"}}, {"family": "Roselli", "given": "Carolina", "initials": "C", "orcid": "0000-0001-5267-6756", "researcher": {"href": "https://publications.scilifelab.se/researcher/1dd28aad250f42719d505c21ed76013b.json"}}, {"family": "Lin", "given": "Honghuang", "initials": "H", "orcid": "0000-0003-3043-3942", "researcher": {"href": "https://publications.scilifelab.se/researcher/9bc2f1e6bb1140dfa054376eac685d5e.json"}}, {"family": "Sveinbj\u00f6rnsson", "given": "Gar\u00f0ar", "initials": "G"}, {"family": "Fatemifar", "given": "Ghazaleh", "initials": "G"}, {"family": "Hedman", "given": "\u00c5sa K", "initials": "\u00c5K"}, {"family": "Wilk", "given": "Jemma B", "initials": "JB"}, {"family": "Morley", "given": "Michael P", "initials": "MP"}, {"family": "Chaffin", "given": "Mark D", "initials": "MD", "orcid": "0000-0002-1234-5562", "researcher": {"href": "https://publications.scilifelab.se/researcher/c73477de5ca0468ab051fd6eab7bad81.json"}}, {"family": "Helgadottir", "given": "Anna", "initials": "A", "orcid": "0000-0002-1806-2467", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b5de2b760674dbfba05df40af0eb38f.json"}}, {"family": "Verweij", "given": "Niek", "initials": "N", "orcid": "0000-0002-4303-7685", "researcher": {"href": "https://publications.scilifelab.se/researcher/7306319d42a640a483b937de588a17a4.json"}}, {"family": "Dehghan", "given": "Abbas", "initials": "A"}, {"family": "Almgren", "given": "Peter", "initials": "P", "orcid": "0000-0002-0473-0241", "researcher": {"href": "https://publications.scilifelab.se/researcher/8c1a61189c4846eaa1de74d1fd79c8bb.json"}}, {"family": "Andersson", "given": "Charlotte", "initials": "C"}, {"family": "Aragam", "given": "Krishna G", "initials": "KG"}, {"family": "\u00c4rnl\u00f6v", "given": "Johan", "initials": "J"}, {"family": "Backman", "given": "Joshua D", "initials": "JD"}, {"family": "Biggs", "given": "Mary L", "initials": "ML"}, {"family": "Bloom", "given": "Heather L", "initials": "HL"}, {"family": "Brandimarto", "given": "Jeffrey", "initials": "J"}, {"family": "Brown", "given": "Michael R", "initials": "MR"}, {"family": "Buckbinder", "given": "Leonard", "initials": "L"}, {"family": "Carey", "given": "David J", "initials": "DJ"}, {"family": "Chasman", "given": "Daniel I", "initials": "DI"}, {"family": "Chen", "given": "Xing", "initials": "X", "orcid": "0000-0002-7299-3238", "researcher": {"href": "https://publications.scilifelab.se/researcher/9d354d5ca83c4059b8151c8e67b99405.json"}}, {"family": "Chen", "given": "Xu", "initials": "X", "orcid": "0000-0002-7299-3238", "researcher": {"href": "https://publications.scilifelab.se/researcher/9d354d5ca83c4059b8151c8e67b99405.json"}}, {"family": "Chung", "given": "Jonathan", "initials": "J"}, {"family": "Chutkow", "given": "William", "initials": "W"}, {"family": "Cook", "given": "James P", "initials": "JP"}, {"family": "Delgado", "given": "Graciela E", "initials": "GE"}, {"family": "Denaxas", "given": "Spiros", "initials": "S"}, {"family": "Doney", "given": "Alexander S", "initials": "AS"}, {"family": "D\u00f6rr", "given": "Marcus", "initials": "M"}, {"family": "Dudley", "given": "Samuel C", "initials": "SC"}, {"family": "Dunn", "given": "Michael E", "initials": "ME"}, {"family": "Engstr\u00f6m", "given": "Gunnar", "initials": "G"}, {"family": "Esko", "given": "T\u00f5nu", "initials": "T"}, {"family": "Felix", "given": "Stephan B", "initials": "SB"}, {"family": "Finan", "given": "Chris", "initials": "C"}, {"family": "Ford", "given": "Ian", "initials": "I"}, {"family": "Ghanbari", "given": "Mohsen", "initials": "M", "orcid": "0000-0002-9476-7143", "researcher": {"href": "https://publications.scilifelab.se/researcher/52ef9606de1144c994e0e854c5a85569.json"}}, {"family": "Ghasemi", "given": "Sahar", "initials": "S"}, {"family": "Giedraitis", "given": "Vilmantas", "initials": "V", "orcid": "0000-0003-3423-2021", "researcher": {"href": "https://publications.scilifelab.se/researcher/7c95879213664e00b66aeee2e8ece975.json"}}, {"family": "Giulianini", "given": "Franco", "initials": "F"}, {"family": "Gottdiener", "given": "John S", "initials": "JS"}, {"family": "Gross", "given": "Stefan", "initials": "S", "orcid": "0000-0003-4121-7161", "researcher": {"href": "https://publications.scilifelab.se/researcher/fde6335a99264403a7f4d01ae7195ebe.json"}}, {"family": "Gu\u00f0bjartsson", "given": "Dan\u00edel F", "initials": "DF", "orcid": "0000-0002-5222-9857", "researcher": {"href": 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{"family": "Smith", "given": "Nicholas L", "initials": "NL"}, {"family": "Stender", "given": "Steen", "initials": "S"}, {"family": "Stott", "given": "David J", "initials": "DJ"}, {"family": "Svensson", "given": "Per", "initials": "P", "orcid": "0000-0003-0372-6272", "researcher": {"href": "https://publications.scilifelab.se/researcher/199e569cd05e456488ead34240b91c5b.json"}}, {"family": "Tammesoo", "given": "Mari-Liis", "initials": "ML"}, {"family": "Taylor", "given": "Kent D", "initials": "KD", "orcid": "0000-0002-2756-4370", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f5450c63d194100ab6cda3b83250fc7.json"}}, {"family": "Teder-Laving", "given": "Maris", "initials": "M", "orcid": "0000-0002-5872-1850", "researcher": {"href": "https://publications.scilifelab.se/researcher/f27feb6c2c23492bb1e442116d0ba49e.json"}}, {"family": "Teumer", "given": "Alexander", "initials": "A", "orcid": "0000-0002-8309-094X", "researcher": {"href": "https://publications.scilifelab.se/researcher/dc9c2667a55b47a6a08aea764fab0946.json"}}, {"family": "Thorgeirsson", "given": "Gu\u00f0mundur", "initials": "G"}, {"family": "Thorsteinsdottir", "given": "Unnur", "initials": "U"}, {"family": "Torp-Pedersen", "given": "Christian", "initials": "C"}, {"family": "Trompet", "given": "Stella", "initials": "S"}, {"family": "Tyl", "given": "Benoit", "initials": "B", "orcid": "0000-0001-5297-8412", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e192aa671144e20916948eaadc4b738.json"}}, {"family": "Uitterlinden", "given": "Andre G", "initials": "AG", "orcid": "0000-0002-7276-3387", "researcher": {"href": "https://publications.scilifelab.se/researcher/273577b238854023a9dffe34dabc3551.json"}}, {"family": "Veluchamy", "given": "Abirami", "initials": "A"}, {"family": "V\u00f6lker", "given": "Uwe", "initials": "U", "orcid": "0000-0002-5689-3448", "researcher": {"href": "https://publications.scilifelab.se/researcher/e529a40052644d83bdef588a3e4f4e99.json"}}, {"family": "Voors", "given": "Adriaan A", "initials": "AA"}, {"family": "Wang", "given": "Xiaosong", "initials": "X"}, {"family": "Wareham", "given": "Nicholas J", "initials": "NJ"}, {"family": "Waterworth", "given": "Dawn", "initials": "D"}, {"family": "Weeke", "given": "Peter E", "initials": "PE"}, {"family": "Weiss", "given": "Raul", "initials": "R"}, {"family": "Wiggins", "given": "Kerri L", "initials": "KL", "orcid": "0000-0003-2749-1279", "researcher": {"href": "https://publications.scilifelab.se/researcher/a9d1f9cb10ef4038abb10fb6ee289504.json"}}, {"family": "Xing", "given": "Heming", "initials": "H"}, {"family": "Yerges-Armstrong", "given": "Laura M", "initials": "LM"}, {"family": "Yu", "given": "Bing", "initials": "B"}, {"family": "Zannad", "given": "Faiez", "initials": "F"}, {"family": "Zhao", "given": "Jing Hua", "initials": "JH"}, {"family": "Hemingway", "given": "Harry", "initials": "H", "orcid": "0000-0003-2279-0624", "researcher": {"href": "https://publications.scilifelab.se/researcher/0bc6b343a8ab4b4c9ff6380d8d4aa626.json"}}, {"family": "Samani", "given": "Nilesh J", "initials": "NJ"}, {"family": "McMurray", "given": "John J V", "initials": "JJV"}, {"family": "Yang", "given": "Jian", "initials": "J", "orcid": "0000-0003-2001-2474", "researcher": {"href": "https://publications.scilifelab.se/researcher/99b6239b59ad42248e8f18583b40777a.json"}}, {"family": "Visscher", "given": "Peter M", "initials": "PM", "orcid": "0000-0002-2143-8760", "researcher": {"href": "https://publications.scilifelab.se/researcher/dcdb41d4720b436494304f74e33206ae.json"}}, {"family": "Newton-Cheh", "given": "Christopher", "initials": "C"}, {"family": "Malarstig", "given": "Anders", "initials": "A"}, {"family": "Holm", "given": "Hilma", "initials": "H"}, {"family": "Lubitz", "given": "Steven A", "initials": "SA", "orcid": "0000-0002-9599-4866", "researcher": {"href": "https://publications.scilifelab.se/researcher/25bb007311104c92983dbcce80f72260.json"}}, {"family": "Sattar", "given": "Naveed", "initials": "N", "orcid": "0000-0002-1604-2593", "researcher": {"href": "https://publications.scilifelab.se/researcher/80fbc7cdcfc444acb066449f80f87181.json"}}, {"family": "Holmes", "given": "Michael V", "initials": "MV"}, {"family": "Cappola", "given": "Thomas P", "initials": "TP", "orcid": "0000-0002-9630-7204", "researcher": {"href": "https://publications.scilifelab.se/researcher/6cc50d241ad14477b91f83e012918181.json"}}, {"family": "Asselbergs", "given": "Folkert W", "initials": "FW", "orcid": "0000-0002-1692-8669", "researcher": {"href": "https://publications.scilifelab.se/researcher/7037429ef1304bdaabd837d242b1e6f5.json"}}, {"family": "Hingorani", "given": "Aroon D", "initials": "AD"}, {"family": "Kuchenbaecker", "given": "Karoline", "initials": "K", "orcid": "0000-0001-9726-603X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e142157c79648ce96b258ea78019829.json"}}, {"family": "Ellinor", "given": "Patrick T", "initials": "PT", "orcid": "0000-0002-2067-0533", "researcher": {"href": "https://publications.scilifelab.se/researcher/dd513dc49e0945bc8298f72d1244648d.json"}}, {"family": "Lang", "given": "Chim C", "initials": "CC"}, {"family": "Stefansson", "given": "Kari", "initials": "K"}, {"family": "Smith", "given": "J Gustav", "initials": "JG"}, {"family": "Vasan", "given": "Ramachandran S", "initials": "RS", "orcid": "0000-0001-7357-5970", "researcher": {"href": "https://publications.scilifelab.se/researcher/50ceef6f00ea4251a5e1e83cd379a506.json"}}, {"family": "Swerdlow", "given": "Daniel I", "initials": "DI"}, {"family": "Lumbers", "given": "R Thomas", "initials": "RT", "orcid": "0000-0002-9077-4741", "researcher": {"href": "https://publications.scilifelab.se/researcher/a53e4d6591db481f881ec6046d54535b.json"}}], "type": "journal article", "published": "2020-01-09", "journal": {"volume": "11", "issn": "2041-1723", "issue": "1", "pages": "163", "title": "Nat Commun", "issn-l": "2041-1723"}, "abstract": "Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies.", "doi": "10.1038/s41467-019-13690-5", "pmid": "31919418", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC6952380"}, {"db": "pii", "key": "10.1038/s41467-019-13690-5"}], "notes": [], "created": "2020-01-14T10:04:57.921Z", "modified": "2023-06-19T13:01:57.741Z"}, {"entity": "publication", "iuid": "61cb2c382f5b4954ae79250a61c45daa", "links": {"self": {"href": "https://publications.scilifelab.se/publication/61cb2c382f5b4954ae79250a61c45daa.json"}, "display": {"href": "https://publications.scilifelab.se/publication/61cb2c382f5b4954ae79250a61c45daa"}}, "title": "DNA methylation changes in Down syndrome derived neural iPSCs uncover co-dysregulation of ZNF and HOX3 families of transcription factors.", "authors": [{"family": "Laan", "given": "Loora", "initials": "L"}, {"family": "Klar", "given": "Joakim", "initials": "J"}, {"family": "Sobol", "given": "Maria", "initials": "M"}, {"family": "Hoeber", "given": "Jan", "initials": "J"}, {"family": "Shahsavani", "given": "Mansoureh", "initials": "M"}, {"family": "Kele", "given": "Malin", "initials": "M"}, {"family": "Fatima", "given": "Ambrin", "initials": "A"}, {"family": "Zakaria", "given": "Muhammad", "initials": "M"}, {"family": "Anner\u00e9n", "given": "G\u00f6ran", "initials": "G"}, {"family": "Falk", "given": "Anna", "initials": "A"}, {"family": "Schuster", "given": "Jens", "initials": "J"}, {"family": "Dahl", "given": "Niklas", "initials": "N", "orcid": "0000-0002-8122-0800", "researcher": {"href": "https://publications.scilifelab.se/researcher/689e06ddc001490a8cb891050ba5a732.json"}}], "type": "comparative study", "published": "2020-01-08", "journal": {"volume": "12", "issn": "1868-7083", "issue": "1", "pages": "9", "title": "Clin Epigenetics", "issn-l": "1868-7075"}, "abstract": "Down syndrome (DS) is characterized by neurodevelopmental abnormalities caused by partial or complete trisomy of human chromosome 21 (T21). Analysis of Down syndrome brain specimens has shown global epigenetic and transcriptional changes but their interplay during early neurogenesis remains largely unknown. We differentiated induced pluripotent stem cells (iPSCs) established from two DS patients with complete T21 and matched euploid donors into two distinct neural stages corresponding to early- and mid-gestational ages.\n\nUsing the Illumina Infinium 450K array, we assessed the DNA methylation pattern of known CpG regions and promoters across the genome in trisomic neural iPSC derivatives, and we identified a total of 500 stably and differentially methylated CpGs that were annotated to CpG islands of 151 genes. The genes were enriched within the DNA binding category, uncovering 37 factors of importance for transcriptional regulation and chromatin structure. In particular, we observed regional epigenetic changes of the transcription factor genes ZNF69, ZNF700 and ZNF763 as well as the HOXA3, HOXB3 and HOXD3 genes. A similar clustering of differential methylation was found in the CpG islands of the HIST1 genes suggesting effects on chromatin remodeling.\n\nThe study shows that early established differential methylation in neural iPSC derivatives with T21 are associated with a set of genes relevant for DS brain development, providing a novel framework for further studies on epigenetic changes and transcriptional dysregulation during T21 neurogenesis.", "doi": "10.1186/s13148-019-0803-1", "pmid": "31915063", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support, Infrastructure and Training": "Service", "Bioinformatics Long-term Support WABI": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s13148-019-0803-1"}, {"db": "pmc", "key": "PMC6950999"}], "notes": [], "created": "2020-01-14T10:04:59.643Z", "modified": "2021-11-10T12:55:02.672Z"}, {"entity": "publication", "iuid": "b4b16d84e520437f8a5e4a67009681c7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b4b16d84e520437f8a5e4a67009681c7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b4b16d84e520437f8a5e4a67009681c7"}}, "title": "A Light-up Logic Platform for Selective Recognition of Parallel G-Quadruplex Structures via Disaggregation-Induced Emission.", "authors": [{"family": "Deiana", "given": "Marco", "initials": "M", "orcid": "0000-0002-7815-4494", "researcher": {"href": "https://publications.scilifelab.se/researcher/f9efbe74ca3940029d782d3ba645fa34.json"}}, {"family": "Chand", "given": "Karam", "initials": "K", "orcid": "0000-0001-7691-4392", "researcher": {"href": "https://publications.scilifelab.se/researcher/a20b7a82f4444b92b3ac1897e2fdb790.json"}}, {"family": "Jamroskovic", "given": "Jan", "initials": "J", "orcid": "0000-0001-6871-7663", "researcher": {"href": "https://publications.scilifelab.se/researcher/154847e2f84f4336a07e219fac6db2f9.json"}}, {"family": "Obi", "given": "Ikenna", "initials": "I", "orcid": "0000-0003-0364-8964", "researcher": {"href": "https://publications.scilifelab.se/researcher/e46c65e7b0e540b0a7c225d54c1502d7.json"}}, {"family": "Chorell", "given": "Erik", "initials": "E", "orcid": "0000-0003-2523-1940", "researcher": {"href": "https://publications.scilifelab.se/researcher/ada783ae0a824621a3b8e1024aae13a4.json"}}, {"family": "Sabouri", "given": "Nasim", "initials": "N", "orcid": "0000-0002-4541-7702", "researcher": {"href": "https://publications.scilifelab.se/researcher/4bdc688dc85a4932acfdfffad8bfc443.json"}}], "type": "journal article", "published": "2020-01-07", "journal": {"volume": "59", "issn": "1521-3773", "issue": "2", "pages": "896-902", "title": "Angew. Chem. Int. Ed. Engl.", "issn-l": "1433-7851"}, "abstract": "The design of turn-on dyes with optical signals sensitive to the formation of supramolecular structures provides fascinating and underexplored opportunities for G-quadruplex (G4) DNA detection and characterization. Here, we show a new switching mechanism that relies on the recognition-driven disaggregation (on-signal) of an ultrabright coumarin-quinazoline conjugate. The synthesized probe selectively lights-up parallel G4 DNA structures via the disassembly of its supramolecular state, demonstrating outputs that are easily integrable into a label-free molecular logic system. Finally, our molecule preferentially stains the G4-rich nucleoli of cancer cells.", "doi": "10.1002/anie.201912027", "pmid": "31644837", "labels": {"Integrated Microscopy Technologies Ume\u00e5": "Service"}, "xrefs": [], "notes": [], "created": "2020-02-12T11:06:01.547Z", "modified": "2021-11-10T12:55:03.771Z"}, {"entity": "publication", "iuid": "24e0c101ab3f49ac830c669e75aa8dfa", "links": {"self": {"href": "https://publications.scilifelab.se/publication/24e0c101ab3f49ac830c669e75aa8dfa.json"}, "display": {"href": "https://publications.scilifelab.se/publication/24e0c101ab3f49ac830c669e75aa8dfa"}}, "title": "Evolutionary History, Genomic Adaptation to Toxic Diet, and Extinction of the Carolina Parakeet.", "authors": [{"family": "Gelabert", "given": "Pere", "initials": "P"}, {"family": "Sandoval-Velasco", "given": "Marcela", "initials": "M"}, {"family": "Serres", "given": "Aitor", "initials": "A"}, {"family": "de Manuel", "given": "Marc", "initials": "M"}, {"family": "Renom", "given": "Pere", "initials": "P"}, {"family": "Margaryan", "given": "Ashot", "initials": "A"}, {"family": "Stiller", "given": "Josefin", "initials": "J"}, {"family": "de-Dios", "given": "Toni", "initials": "T"}, {"family": "Fang", "given": "Qi", "initials": "Q"}, {"family": "Feng", "given": "Shaohong", "initials": "S"}, {"family": "Ma\u00f1osa", "given": "Santi", "initials": "S"}, {"family": "Pacheco", "given": "George", "initials": "G"}, {"family": "Ferrando-Bernal", "given": "Manuel", "initials": "M"}, {"family": "Shi", "given": "Guolin", "initials": "G"}, {"family": "Hao", "given": "Fei", "initials": "F"}, {"family": "Chen", "given": "Xianqing", "initials": "X"}, {"family": "Petersen", "given": "Bent", "initials": "B"}, {"family": "Olsen", "given": "Remi-Andr\u00e9", "initials": "RA"}, {"family": "Navarro", "given": "Arcadi", "initials": "A"}, {"family": "Deng", "given": "Yuan", "initials": "Y"}, {"family": "Dal\u00e9n", "given": "Love", "initials": "L", "orcid": "0000-0001-8270-7613", "researcher": {"href": "https://publications.scilifelab.se/researcher/48ecf726779249ac9d12f4f7a1cc62bf.json"}}, {"family": "Marqu\u00e8s-Bonet", "given": "Tom\u00e0s", "initials": "T"}, {"family": "Zhang", "given": "Guojie", "initials": "G"}, {"family": "Antunes", "given": "Agostinho", "initials": "A"}, {"family": "Gilbert", "given": "M Thomas P", "initials": "MTP"}, {"family": "Lalueza-Fox", "given": "Carles", "initials": "C"}], "type": "journal article", "published": "2020-01-06", "journal": {"volume": "30", "issn": "1879-0445", "issue": "1", "pages": "108-114.e5", "title": "Curr. Biol.", "issn-l": "0960-9822"}, "abstract": "As the only endemic neotropical parrot to have recently lived in the northern hemisphere, the Carolina parakeet (Conuropsis carolinensis) was an iconic North American bird. The last surviving specimen died in the Cincinnati Zoo in 1918 [1]. The cause of its extinction remains contentious: besides excessive mortality associated to habitat destruction and active hunting, their survival could have been negatively affected by its range having become increasingly patchy [2] or by the exposure to poultry pathogens [3, 4]. In addition, the Carolina parakeet showed a predilection for cockleburs, an herbaceous plant that contains a powerful toxin, carboxyatractyloside, or CAT [5], which did not seem to affect them but made the birds notoriously toxic to most predators [3]. To explore the demographic history of this bird, we generated the complete genomic sequence of a preserved specimen held in a private collection in Espinelves (Girona, Spain), as well as of a close extant relative, Aratinga solstitialis. We identified two non-synonymous genetic changes in two highly conserved proteins known to interact with CAT that could underlie a specific dietary adaptation to this toxin. Our genomic analyses did not reveal evidence of a dramatic past demographic decline in the Carolina parakeet; also, its genome did not exhibit the long runs of homozygosity that are signals of recent inbreeding and are typically found in endangered species. As such, our results suggest its extinction was an abrupt process and thus likely solely attributable to human causes.", "doi": "10.1016/j.cub.2019.10.066", "pmid": "31839456", "labels": {"National Genomics Infrastructure": "Collaborative", "NGI Stockholm (Genomics Applications)": "Collaborative", "NGI Stockholm (Genomics Production)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0960-9822(19)31438-1"}], "notes": [], "created": "2020-01-08T16:49:21.462Z", "modified": "2021-11-10T12:55:04.959Z"}, {"entity": "publication", "iuid": "b96de159533f4323af11797464cfbc81", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b96de159533f4323af11797464cfbc81.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b96de159533f4323af11797464cfbc81"}}, "title": "Metabolic Profiling and Compound-Class Identification Reveal Alterations in Serum Triglyceride Levels in Mice Immunized with Human Vaccine Adjuvant Alum.", "authors": [{"family": "Khoomrung", "given": "Sakda", "initials": "S", "orcid": "0000-0001-9461-8597", "researcher": {"href": "https://publications.scilifelab.se/researcher/edd185d1e13f44ee9b3ea0a1925cabe1.json"}}, {"family": "Nookaew", "given": "Intawat", "initials": "I"}, {"family": "Sen", "given": "Partho", "initials": "P"}, {"family": "Olafsdottir", "given": "Thorunn A", "initials": "TA"}, {"family": "Persson", "given": "Josefine", "initials": "J"}, {"family": "Moritz", "given": "Thomas", "initials": "T", "orcid": "0000-0002-4258-3190", "researcher": {"href": "https://publications.scilifelab.se/researcher/95ad5b7fe48f42eda1328f54a385e097.json"}}, {"family": "Andersen", "given": "Peter", "initials": "P"}, {"family": "Harandi", "given": "Ali M", "initials": "AM"}, {"family": "Nielsen", "given": "Jens", "initials": "J", "orcid": "0000-0002-9955-6003", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a596e289be4438a8a2653b1f25fea8b.json"}}], "type": "journal article", "published": "2020-01-03", "journal": {"title": "J. Proteome Res.", "issn": "1535-3907", "volume": "19", "issue": "1", "pages": "269-278", "issn-l": "1535-3893"}, "abstract": "Alum has been widely used as an adjuvant for human vaccines; however, the impact of Alum on host metabolism remains largely unknown. Herein, we applied mass spectrometry (MS) (liquid chromatography-MS)-based metabolic and lipid profiling to monitor the effects of the Alum adjuvant on mouse serum at 6, 24, 72, and 168 h post-vaccination. We propose a new strategy termed subclass identification and annotation for metabolomics for class-wise identification of untargeted metabolomics data generated from high-resolution MS. Using this approach, we identified and validated the levels of several lipids in mouse serum that were significantly altered following Alum administration. These lipids showed a biphasic response even 168 h after vaccination. The majority of the lipids were triglycerides (TAGs), where TAGs with long-chain unsaturated fatty acids (FAs) decreased at 24 h and TAGs with short-chain FAs decreased at 168 h. To our knowledge, this is the first report on the impact of human vaccine adjuvant Alum on the host metabolome, which may provide new insights into the mechanism of action of Alum.", "doi": "10.1021/acs.jproteome.9b00517", "pmid": "31625748", "labels": {"Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7735194"}, {"db": "mid", "key": "NIHMS1647517"}], "notes": [], "created": "2020-01-21T10:14:14.275Z", "modified": "2025-10-17T13:03:16.936Z"}, {"entity": "publication", "iuid": "9b592e44470a4ba18b57b727b2011b71", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9b592e44470a4ba18b57b727b2011b71.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9b592e44470a4ba18b57b727b2011b71"}}, "title": "Integrative discovery of treatments for high-risk neuroblastoma.", "authors": [{"family": "Almstedt", "given": "Elin", "initials": "E", "orcid": "0000-0002-1946-9138", "researcher": {"href": "https://publications.scilifelab.se/researcher/c4414ac7f9284bf9bf0b52530ec19ee3.json"}}, {"family": "Elgendy", "given": "Ramy", "initials": "R", "orcid": "0000-0002-2592-3448", "researcher": {"href": "https://publications.scilifelab.se/researcher/0a5ce4db4317446bb1ef113f7c6e8eb5.json"}}, {"family": "Hekmati", "given": "Neda", "initials": "N"}, {"family": "Ros\u00e9n", "given": "Emil", "initials": "E", "orcid": "0000-0002-1664-2257", "researcher": {"href": "https://publications.scilifelab.se/researcher/db0751a3a95e488bb849059c09c4fc7d.json"}}, {"family": "W\u00e4rn", "given": "Caroline", "initials": "C"}, {"family": "Olsen", "given": "Thale Kristin", "initials": "TK"}, {"family": "Dyberg", "given": "Cecilia", "initials": "C"}, {"family": "Doroszko", "given": "Milena", "initials": "M"}, {"family": "Larsson", "given": "Ida", "initials": "I", "orcid": "0000-0001-5422-4243", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ac604ca793048e9b6ddaa3459b4e97a.json"}}, {"family": "Sundstr\u00f6m", "given": "Anders", "initials": "A"}, {"family": "Arsenian Henriksson", "given": "Marie", "initials": "M"}, {"family": "P\u00e5hlman", "given": "Sven", "initials": "S"}, {"family": "Bexell", "given": "Daniel", "initials": "D", "orcid": "0000-0001-9426-9550", "researcher": {"href": "https://publications.scilifelab.se/researcher/dda650768a264d93a80f40da6cb8d7e1.json"}}, {"family": "Vanlandewijck", "given": "Michael", "initials": "M", "orcid": "0000-0002-0709-7808", "researcher": {"href": "https://publications.scilifelab.se/researcher/aa2148fbafb44d59bd110e36bd77769c.json"}}, {"family": "Kogner", "given": "Per", "initials": "P", "orcid": "0000-0002-2202-9694", "researcher": {"href": "https://publications.scilifelab.se/researcher/e963274b921a4a2c8263f509334d4e22.json"}}, {"family": "J\u00f6rnsten", "given": "Rebecka", "initials": "R"}, {"family": "Krona", "given": "Cecilia", "initials": "C"}, {"family": "Nelander", "given": "Sven", "initials": "S"}], "type": "journal article", "published": "2020-01-03", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "11", "issue": "1", "pages": "71"}, "abstract": "Despite advances in the molecular exploration of paediatric cancers, approximately 50% of children with high-risk neuroblastoma lack effective treatment. To identify therapeutic options for this group of high-risk patients, we combine predictive data mining with experimental evaluation in patient-derived xenograft cells. Our proposed algorithm, TargetTranslator, integrates data from tumour biobanks, pharmacological databases, and cellular networks to predict how targeted interventions affect mRNA signatures associated with high patient risk or disease processes. We find more than 80 targets to be associated with neuroblastoma risk and differentiation signatures. Selected targets are evaluated in cell lines derived from high-risk patients to demonstrate reversal of risk signatures and malignant phenotypes. Using neuroblastoma xenograft models, we establish CNR2 and MAPK8 as promising candidates for the treatment of high-risk neuroblastoma. We expect that our method, available as a public tool (targettranslator.org), will enhance and expedite the discovery of risk-associated targets for paediatric and adult cancers.", "doi": "10.1038/s41467-019-13817-8", "pmid": "31900415", "labels": {"Genome Engineering Zebrafish": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41467-019-13817-8"}, {"db": "pmc", "key": "PMC6941971"}], "notes": [], "created": "2020-01-08T11:24:16.666Z", "modified": "2021-12-09T14:05:49.139Z"}, {"entity": "publication", "iuid": "a6bc07a0f8a546cfa3841bdb3032ec2e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a6bc07a0f8a546cfa3841bdb3032ec2e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a6bc07a0f8a546cfa3841bdb3032ec2e"}}, "title": "The Mitogenome of Norway Spruce and a Reappraisal of Mitochondrial Recombination in Plants.", "authors": [{"family": "Sullivan", "given": "Alexis R", "initials": "AR", "orcid": "0000-0003-2182-911X", "researcher": {"href": "https://publications.scilifelab.se/researcher/82ef3b1f7aec4a99864cd60cad55507e.json"}}, {"family": "Eldfjell", "given": "Yrin", "initials": "Y"}, {"family": "Schiffthaler", "given": "Bastian", "initials": "B", "orcid": "0000-0002-9771-467X", "researcher": {"href": "https://publications.scilifelab.se/researcher/12527c57f62e4a46b758e061ba3f80b1.json"}}, {"family": "Delhomme", "given": "Nicolas", "initials": "N", "orcid": "0000-0002-3053-0796", "researcher": {"href": "https://publications.scilifelab.se/researcher/107fbbd40f1444fb838ad4c0365738fa.json"}}, {"family": "Asp", "given": "Torben", "initials": "T", "orcid": "0000-0002-6470-2410", "researcher": {"href": "https://publications.scilifelab.se/researcher/fcb35e5ec7f644848c5bfabc5ed79bc3.json"}}, {"family": "Hebelstrup", "given": "Kim H", "initials": "KH", "orcid": "0000-0002-3984-3633", "researcher": {"href": "https://publications.scilifelab.se/researcher/cfc2c2091d4d4ab0998f76118ae2bbf6.json"}}, {"family": "Keech", "given": "Olivier", "initials": "O", "orcid": "0000-0002-0546-7721", "researcher": {"href": "https://publications.scilifelab.se/researcher/cbfa829eb0b74b67aed7865dda0e15d3.json"}}, {"family": "\u00d6berg", "given": "Lisa", "initials": "L"}, {"family": "M\u00f8ller", "given": "Ian Max", "initials": "IM", "orcid": "0000-0002-7919-7787", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae0f45488d984c95b7c37b57d9b559cb.json"}}, {"family": "Arvestad", "given": "Lars", "initials": "L", "orcid": "0000-0001-5341-1733", "researcher": {"href": "https://publications.scilifelab.se/researcher/27184c3c97f2457893e5232544efee24.json"}}, {"family": "Street", "given": "Nathaniel R", "initials": "NR", "orcid": "0000-0001-6031-005X", "researcher": {"href": "https://publications.scilifelab.se/researcher/cb9ceb237a724046a1454179a32de1b0.json"}}, {"family": "Wang", "given": "Xiao-Ru", "initials": "XR", "orcid": "0000-0002-6150-7046", "researcher": {"href": "https://publications.scilifelab.se/researcher/186f7b1871404673a12544f5bbf7409f.json"}}], "type": "journal article", "published": "2020-01-01", "journal": {"title": "Genome Biol Evol", "issn": "1759-6653", "volume": "12", "issue": "1", "pages": "3586-3598", "issn-l": "1759-6653"}, "abstract": "Plant mitogenomes can be difficult to assemble because they are structurally dynamic and prone to intergenomic DNA transfers, leading to the unusual situation where an organelle genome is far outnumbered by its nuclear counterparts. As a result, comparative mitogenome studies are in their infancy and some key aspects of genome evolution are still known mainly from pregenomic, qualitative methods. To help address these limitations, we combined machine learning and in silico enrichment of mitochondrial-like long reads to assemble the bacterial-sized mitogenome of Norway spruce (Pinaceae: Picea abies). We conducted comparative analyses of repeat abundance, intergenomic transfers, substitution and rearrangement rates, and estimated repeat-by-repeat homologous recombination rates. Prompted by our discovery of highly recombinogenic small repeats in P. abies, we assessed the genomic support for the prevailing hypothesis that intramolecular recombination is predominantly driven by repeat length, with larger repeats facilitating DNA exchange more readily. Overall, we found mixed support for this view: Recombination dynamics were heterogeneous across vascular plants and highly active small repeats (ca. 200 bp) were present in about one-third of studied mitogenomes. As in previous studies, we did not observe any robust relationships among commonly studied genome attributes, but we identify variation in recombination rates as a underinvestigated source of plant mitogenome diversity.", "doi": "10.1093/gbe/evz263", "pmid": "31774499", "labels": {"NGI Uppsala (Uppsala Genome Center)": "Service", "National Genomics Infrastructure": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "5644343"}, {"db": "pmc", "key": "PMC6944214"}], "notes": [], "created": "2020-09-15T06:47:15.995Z", "modified": "2024-01-16T13:48:43.093Z"}, {"entity": "publication", "iuid": "f591fb00201c499e85e74b11ee304e39", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f591fb00201c499e85e74b11ee304e39.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f591fb00201c499e85e74b11ee304e39"}}, "title": "The Genome of the Endangered Dryas Monkey Provides New Insights into the Evolutionary History of the Vervets.", "authors": [{"family": "van der Valk", "given": "Tom", "initials": "T", "orcid": "0000-0001-6582-3452", "researcher": {"href": "https://publications.scilifelab.se/researcher/f56ca19cfa4f4909be996b2c99ec24f1.json"}}, {"family": "Gonda", "given": "Catalina M", "initials": "CM"}, {"family": "Silegowa", "given": "Henri", "initials": "H"}, {"family": "Almanza", "given": "Sandra", "initials": "S"}, {"family": "Sifuentes-Romero", "given": "Itzel", "initials": "I"}, {"family": "Hart", "given": "Terese B", "initials": "TB"}, {"family": "Hart", "given": "John A", "initials": "JA"}, {"family": "Detwiler", "given": "Kate M", "initials": "KM"}, {"family": "Guschanski", "given": "Katerina", "initials": "K"}], "type": "journal article", "published": "2020-01-01", "journal": {"title": "Mol. Biol. Evol.", "issn": "1537-1719", "volume": "37", "issue": "1", "pages": "183-194", "issn-l": "0737-4038"}, "abstract": "Genomic data can be a powerful tool for inferring ecology, behavior, and conservation needs of highly elusive species, particularly, when other sources of information are hard to come by. Here, we focus on the Dryas monkey (Cercopithecus dryas), an endangered primate endemic to the Congo Basin with cryptic behavior and possibly <250 remaining adult individuals. Using whole-genome sequencing data, we show that the Dryas monkey represents a sister lineage to the vervets (Chlorocebus sp.) and has diverged from them \u223c1.4 Ma with additional bidirectional gene flow \u223c750,000-\u223c500,000 years ago that has likely involved the crossing of the Congo River. Together with evidence of gene flow across the Congo River in bonobos and okapis, our results suggest that the fluvial topology of the Congo River might have been more dynamic than previously recognized. Despite the presence of several homozygous loss-of-function mutations in genes associated with sperm mobility and immunity, we find high genetic diversity and low levels of inbreeding and genetic load in the studied Dryas monkey individual. This suggests that the current population carries sufficient genetic variability for long-term survival and might be larger than currently recognized. We thus provide an example of how genomic data can directly improve our understanding of highly elusive species.", "doi": "10.1093/molbev/msz213", "pmid": "31529046", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "5570178"}, {"db": "pmc", "key": "PMC6984364"}], "notes": [], "created": "2020-02-12T07:40:44.973Z", "modified": "2024-01-16T13:48:43.100Z"}, {"entity": "publication", "iuid": "0e4e002f20e24243b41ee6a1353b21a5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0e4e002f20e24243b41ee6a1353b21a5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0e4e002f20e24243b41ee6a1353b21a5"}}, "title": "Hepatitis E virus genotype 3 strains and a plethora of other viruses detected in raw and still in tap water.", "authors": [{"family": "Wang", "given": "Hao", "initials": "H", "orcid": "0000-0001-9425-4666", "researcher": {"href": "https://publications.scilifelab.se/researcher/e38bb81715854f71977b1c4629cc5031.json"}}, {"family": "Kjellberg", "given": "Inger", "initials": "I"}, {"family": "Sikora", "given": "Per", "initials": "P", "orcid": "0000-0002-0049-1562", "researcher": {"href": "https://publications.scilifelab.se/researcher/beeaccd4a7ab4105be077ee778cf0507.json"}}, {"family": "Rydberg", "given": "Henrik", "initials": "H"}, {"family": "Lindh", "given": "Magnus", "initials": "M"}, {"family": "Bergstedt", "given": "Olof", "initials": "O"}, {"family": "Norder", "given": "Hel\u00e9ne", "initials": "H", "orcid": "0000-0002-7528-3872", "researcher": {"href": "https://publications.scilifelab.se/researcher/96f9ac68626f4796840da78e72940193.json"}}], "type": "journal article", "published": "2020-01-01", "journal": {"volume": "168", "issn": "1879-2448", "issue": null, "pages": "115141", "title": "Water Res.", "issn-l": "0043-1354"}, "abstract": "In this study, next generation sequencing was used to explore the virome in 20L up to 10,000L water from different purification steps at two Swedish drinking water treatment plants (DWTPs), and in tap water. One DWTP used ultrafiltration (UF) with 20 nm pores, the other UV light treatment after conventional treatment of the water. Viruses belonging to 26 different families were detected in raw water, in which 6-9 times more sequence reads were found for phages than for known environmental, plant or vertebrate viruses. The total number of viral reads was reduced more than 4-log10 after UF and 3-log10 over UV treatment. However, for some viruses the reduction was 3.5-log10 after UF, as for hepatitis E virus (HEV), which was also detected in tap water, with sequences similar to those in raw water and after treatment. This indicates that HEV had passed through the treatment and entered into the supply network. However, the viability of the viruses is unknown. In tap water 10-130 International Units of HEV RNA/mL were identified, which is a comparable low amount of virus. The risk of getting infected through consumption of tap water is probably negligible, but needs to be investigated. The HEV strains in the waters belonged to subtypes HEV3a and HEV3c/i, which is associated with unknown source of infection in humans infected in Sweden. None of these subtypes are common among pigs or wild boar, the major reservoirs for HEV, indicating that water may play a role in transmitting this virus. The results indicate that monitoring small fecal/oral transmitted viruses in DWTPs may be considered, especially during community outbreaks, to prevent potential transmission by tap water.", "doi": "10.1016/j.watres.2019.115141", "pmid": "31590036", "labels": {"Clinical Genomics Gothenburg": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0043-1354(19)30915-7"}], "notes": [], "created": "2020-02-11T11:03:28.877Z", "modified": "2022-03-29T13:37:58.675Z"}, {"entity": "publication", "iuid": "b113002942174b6b8c2f67907d1d2182", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b113002942174b6b8c2f67907d1d2182.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b113002942174b6b8c2f67907d1d2182"}}, "title": "Discovery of Novel Sequences in 1,000 Swedish Genomes.", "authors": [{"family": "Eisfeldt", "given": "Jesper", "initials": "J", "orcid": "0000-0003-3716-4917", "researcher": {"href": "https://publications.scilifelab.se/researcher/32a701ee07674785b48b047665e18ee6.json"}}, {"family": "M\u00e5rtensson", "given": "Gustaf", "initials": "G"}, {"family": "Ameur", "given": "Adam", "initials": "A", "orcid": "0000-0001-6085-6749", "researcher": {"href": "https://publications.scilifelab.se/researcher/e960811513664a78b2804a00ee70f7c3.json"}}, {"family": "Nilsson", "given": "Daniel", "initials": "D", "orcid": "0000-0001-5831-385X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b3f854e51704270831e155518265ea6.json"}}, {"family": "Lindstrand", "given": "Anna", "initials": "A", "orcid": "0000-0003-0806-5602", "researcher": {"href": "https://publications.scilifelab.se/researcher/07f3e6152da043d38c7a81974fcf8c23.json"}}], "type": "journal article", "published": "2020-01-01", "journal": {"volume": "37", "issn": "1537-1719", "issue": "1", "pages": "18-30", "title": "Mol. Biol. Evol.", "issn-l": "0737-4038"}, "abstract": "Novel sequences (NSs), not present in the human reference genome, are abundant and remain largely unexplored. Here, we utilize de novo assembly to study NS in 1,000 Swedish individuals first sequenced as part of the SweGen project revealing a total of 46 Mb in 61,044 distinct contigs of sequences not present in GRCh38. The contigs were aligned to recently published catalogs of Icelandic and Pan-African NSs, as well as the chimpanzee genome, revealing a great diversity of shared sequences. Analyzing the positioning of NS across the chimpanzee genome, we find that 2,807 NS align confidently within 143 chimpanzee orthologs of human genes. Aligning the whole genome sequencing data to the chimpanzee genome, we discover ancestral NS common throughout the Swedish population. The NSs were searched for repeats and repeat elements: revealing a majority of repetitive sequence (56%), and enrichment of simple repeats (28%) and satellites (15%). Lastly, we align the unmappable reads of a subset of the thousand genomes data to our collection of NS, as well as the previously published Pan-African NS: revealing that both the Swedish and Pan-African NS are widespread, and that the Swedish NSs are largely a subset of the Pan-African NS. Overall, these results highlight the importance of creating a more diverse reference genome and illustrate that significant amounts of the NS may be of ancestral origin.", "doi": "10.1093/molbev/msz176", "pmid": "31560401", "labels": {"NGI Stockholm (Genomics Production)": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "NGI Uppsala (Uppsala Genome Center)": "Collaborative", "National Genomics Infrastructure": "Collaborative", "NGI Stockholm (Genomics Applications)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "5555682"}, {"db": "pmc", "key": "PMC6984370"}], "notes": [], "created": "2019-10-30T08:45:30.942Z", "modified": "2024-01-16T13:48:43.107Z"}, {"entity": "publication", "iuid": "a848d7abba564fcea3890c5331d71787", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a848d7abba564fcea3890c5331d71787.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a848d7abba564fcea3890c5331d71787"}}, "title": "A dual-action peptide-containing hydrogel targets wound infection and inflammation.", "authors": [{"family": "Puthia", "given": "Manoj", "initials": "M", "orcid": "0000-0001-6048-7234", "researcher": {"href": "https://publications.scilifelab.se/researcher/f794b8d0d66a4bab964e915ff71a7023.json"}}, {"family": "Butrym", "given": "Marta", "initials": "M"}, {"family": "Petrlova", "given": "Jitka", "initials": "J"}, {"family": "Str\u00f6mdahl", "given": "Ann-Charlotte", "initials": "AC"}, {"family": "Andersson", "given": "Madelene \u00c5", "initials": "M\u00c5"}, {"family": "Kjellstr\u00f6m", "given": "Sven", "initials": "S"}, {"family": "Schmidtchen", "given": "Artur", "initials": "A", "orcid": "0000-0001-9209-3141", "researcher": {"href": "https://publications.scilifelab.se/researcher/406510dc3844487e9c45f713ea173b8e.json"}}], "type": "journal article", "published": "2020-01-01", "journal": {"volume": "12", "issn": "1946-6242", "issue": "524", "pages": "eaax6601", "title": "Sci Transl Med", "issn-l": "1946-6234"}, "abstract": "There is a clinical need for improved wound treatments that prevent both infection and excessive inflammation. TCP-25, a thrombin-derived peptide, is antibacterial and scavenges pathogen-associated molecular patterns (PAMPs), such as lipopolysaccharide, thereby preventing CD14 interaction and Toll-like receptor dimerization, leading to reduced downstream immune activation. Here, we describe the development of a hydrogel formulation that was functionalized with TCP-25 to target bacteria and associated PAMP-induced inflammation. In vitro studies determined the polymer prerequisites for such TCP-25-mediated dual action, favoring the use of noncharged hydrophilic hydrogels, which enabled peptide conformational changes and LPS binding. The TCP-25-functionalized hydrogels killed Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa bacteria in vitro, as well as in experimental mouse models of subcutaneous infection. The TCP-25 hydrogel also mediated reduction of LPS-induced local inflammatory responses, as demonstrated by analysis of local cytokine production and in vivo bioimaging using nuclear factor \u03baB (NF-\u03baB) reporter mice. In porcine partial thickness wound models, TCP-25 prevented infection with S. aureus and reduced concentrations of proinflammatory cytokines. Proteolytic fragmentation of TCP-25 in vitro yielded a series of bioactive TCP fragments that were identical or similar to those present in wounds in vivo. Together, the results demonstrate the therapeutic potential of TCP-25 hydrogel, a wound treatment based on the body's peptide defense, for prevention of both bacterial infection and the accompanying inflammation.", "doi": "10.1126/scitranslmed.aax6601", "pmid": "31894104", "labels": {"Structural Proteomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "12/524/eaax6601"}], "notes": [], "created": "2020-01-27T10:00:04.983Z", "modified": "2021-11-10T12:55:13.158Z"}, {"entity": "publication", "iuid": "72a503969cf644bfb111a0651557793a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/72a503969cf644bfb111a0651557793a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/72a503969cf644bfb111a0651557793a"}}, "title": "Whole genome sequencing of apparently mutation-negative MEN1 patients.", "authors": [{"family": "Backman", "given": "Samuel", "initials": "S"}, {"family": "Bajic", "given": "Duska", "initials": "D"}, {"family": "Crona", "given": "Joakim", "initials": "J"}, {"family": "Hellman", "given": "Per", "initials": "P"}, {"family": "Skogseid", "given": "Britt", "initials": "B"}, {"family": "St\u00e5lberg", "given": "Peter", "initials": "P"}], "type": "journal article", "published": "2020-01-00", "journal": {"title": "Eur. J. Endocrinol.", "issn": "1479-683X", "issn-l": "0804-4643", "volume": "182", "issue": "1", "pages": "35-45"}, "abstract": "Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant syndrome usually caused by loss-of-function mutations in the MEN1 gene. However, a minority of patients who fulfill the criteria for MEN1 are not found to harbor MEN1 mutations. Besides, some of these individuals, present with a subtly different phenotype suggestive of sporadic disease. The aim of the present study was to investigate the genetic architecture of mutation-negative MEN1.\n\nFourteen patients with a clinical diagnosis (n = 13) or suspicion (n = 1) of MEN1 who had negative genetic screening of the MEN1 gene were included.\n\nConstitutional DNA from the included patients, as well as tumor DNA from six of the patients, was subjected to whole genome sequencing. Constitutional variants were filtered against population databases and somatic variants were studied under a tumor-suppressor model.\n\nThree patients carried pathogenic variants (two splice-site variants, one missense variant) in MEN1 that had not been detected during routine clinical sequencing, one patient carried a pathogenic variant in CASR and one patient carried a gross deletion on chromosome 1q which included the CDC73 gene. Analysis of matched tumor DNA from six patients without mutations did not detect any recurrent genes fulfilling Knudson's two-hit model.\n\nThese results highlight the possibility of germline mutations being missed in routine screening, the importance of considering phenocopies in atypical or mutation-negative cases. The absence of apparent disease-causing mutations suggests that a fraction of MEN1 mutation-negative MEN1 cases may be due to the chance occurrence of several endocrine tumors in one patient.", "doi": "10.1530/EJE-19-0522", "pmid": "31658439", "labels": {"Bioinformatics Support, Infrastructure and Training": "Service", "Bioinformatics Support and Infrastructure": "Service", "National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Service"}, "xrefs": [{"db": "pii", "key": "EJE-19-0522"}], "notes": [], "created": "2020-01-08T14:27:31.627Z", "modified": "2024-01-16T13:48:43.114Z"}, {"entity": "publication", "iuid": "6096e926f8b84db291d25f029ecd581c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6096e926f8b84db291d25f029ecd581c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6096e926f8b84db291d25f029ecd581c"}}, "title": "Variable neurodevelopmental and morphological phenotypes of carriers with 12q12 duplications.", "authors": [{"family": "Myers", "given": "Lynnea", "initials": "L"}, {"family": "Blyth", "given": "Moira", "initials": "M"}, {"family": "Moradkhani", "given": "Kamran", "initials": "K"}, {"family": "Hranilovi\u0107", "given": "Dubravka", "initials": "D"}, {"family": "Polesie", "given": "Sam", "initials": "S"}, {"family": "Isaksson", "given": "Johan", "initials": "J"}, {"family": "Nordgren", "given": "Ann", "initials": "A"}, {"family": "Bucan", "given": "Maja", "initials": "M"}, {"family": "Vincent", "given": "Marie", "initials": "M"}, {"family": "B\u00f6lte", "given": "Sven", "initials": "S"}, {"family": "Anderlid", "given": "Britt-Marie", "initials": "BM"}, {"family": "Tammimies", "given": "Kristiina", "initials": "K", "orcid": "0000-0002-8324-4697", "researcher": {"href": "https://publications.scilifelab.se/researcher/ba19ec07147743c6942ea10c9a92482a.json"}}], "type": "case reports", "published": "2020-01-00", "journal": {"title": "Mol Genet Genomic Med", "issn": "2324-9269", "volume": "8", "issue": "1", "pages": "e1013", "issn-l": "2324-9269"}, "abstract": "Variable size deletions affecting 12q12 have been found in individuals with neurodevelopmental disorders (NDDs) and distinct facial and physical features. For many genetic loci affected by deletions in individuals with NDDs, reciprocal duplications have been described. However, for the 12q12 region, there are no detailed descriptions of duplication cases in the literature.\n\nWe report a phenotypic description of a family with monozygotic twins diagnosed with NDDs, carrying a 9 Mb duplication at 12q12, and five other individuals with overlapping duplications ranging from 4.54 Mb up to 15.16 Mb.\n\nThe duplication carriers had language delays, cognitive delays, and were diagnosed with autism spectrum disorder. Additionally, distinct facial features (e.g., high foreheads, deeply set eyes, short palpebral fissures, small ears, high nasal bridges, abnormalities of the nose tip, thin lips), large feet, and abnormalities in the digits were noted. We also describe incomplete penetrance of the NDD phenotypes among the individuals with 12q12 duplication.\n\nThis case series expands our knowledge on this rare genetic aberration and suggests that large 12q12 duplications may increase the risk for developing NDDs.", "doi": "10.1002/mgg3.1013", "pmid": "31730283", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC6978403"}], "notes": [], "created": "2020-03-03T12:57:26.226Z", "modified": "2024-01-16T13:48:43.121Z"}, {"entity": "publication", "iuid": "55f4ed329d83487cb94e14dbd80050fc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/55f4ed329d83487cb94e14dbd80050fc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/55f4ed329d83487cb94e14dbd80050fc"}}, "title": "The Proteome of the Dentate Terminal Zone of the Perforant Path Indicates Presynaptic Impairment in Alzheimer Disease.", "authors": [{"family": "Haytural", "given": "Hazal", "initials": "H", "orcid": "0000-0002-6805-6989", "researcher": {"href": "https://publications.scilifelab.se/researcher/863ccd2db6794dff8e36a313075e4ea2.json"}}, {"family": "Mermelekas", "given": "Georgios", "initials": "G"}, {"family": "Emre", "given": "Ceren", "initials": "C"}, {"family": "Nigam", "given": "Saket Milind", "initials": "SM"}, {"family": "Carroll", "given": "Steven L", "initials": "SL"}, {"family": "Winblad", "given": "Bengt", "initials": "B"}, {"family": "Bogdanovic", "given": "Nenad", "initials": "N"}, {"family": "Barthet", "given": "Ga\u00ebl", "initials": "G", "orcid": "0000-0003-4025-1616", "researcher": {"href": "https://publications.scilifelab.se/researcher/405b338627c64906b897ff3b394ce531.json"}}, {"family": "Granholm", "given": "Ann-Charlotte", "initials": "AC"}, {"family": "Orre", "given": "Lukas M", "initials": "LM", "orcid": "0000-0002-0384-1003", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b4e49a93b0143db88059c4d1e9fdc59.json"}}, {"family": "Tjernberg", "given": "Lars O", "initials": "LO"}, {"family": "Frykman", "given": "Susanne", "initials": "S"}], "type": "journal article", "published": "2020-01-00", "journal": {"volume": "19", "issn": "1535-9484", "issue": "1", "pages": "128-141", "title": "Mol. Cell Proteomics", "issn-l": "1535-9476"}, "abstract": "Synaptic dysfunction is an early pathogenic event in Alzheimer disease (AD) that contributes to network disturbances and cognitive decline. Some synapses are more vulnerable than others, including the synapses of the perforant path, which provides the main excitatory input to the hippocampus. To elucidate the molecular mechanisms underlying the dysfunction of these synapses, we performed an explorative proteomic study of the dentate terminal zone of the perforant path. The outer two-thirds of the molecular layer of the dentate gyrus, where the perforant path synapses are located, was microdissected from five subjects with AD and five controls. The microdissected tissues were dissolved and digested by trypsin. Peptides from each sample were labeled with different isobaric tags, pooled together and pre-fractionated into 72 fractions by high-resolution isoelectric focusing. Each fraction was then analyzed by liquid chromatography-mass spectrometry. We quantified the relative expression levels of 7322 proteins, whereof 724 showed significantly altered levels in AD. Our comprehensive data analysis using enrichment and pathway analyses strongly indicated that presynaptic signaling, such as exocytosis and synaptic vesicle cycle processes, is severely disturbed in this area in AD, whereas postsynaptic proteins remained unchanged. Among the significantly altered proteins, we selected three of the most downregulated synaptic proteins; complexin-1, complexin-2 and synaptogyrin-1, for further validation, using a new cohort consisting of six AD and eight control cases. Semi-quantitative analysis of immunohistochemical staining confirmed decreased levels of complexin-1, complexin-2 and synaptogyrin-1 in the outer two-thirds of the molecular layer of the dentate gyrus in AD. Our in-depth proteomic analysis provides extensive knowledge on the potential molecular mechanism underlying synaptic dysfunction related to AD and supports that presynaptic alterations are more important than postsynaptic changes in early stages of the disease. The specific synaptic proteins identified could potentially be targeted to halt synaptic dysfunction in AD.", "doi": "10.1074/mcp.RA119.001737", "pmid": "31699905", "labels": {"Global Proteomics and Proteogenomics": "Collaborative", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S1535-9476(20)30010-4"}, {"db": "pmc", "key": "PMC6944231"}], "notes": [], "created": "2020-01-07T09:41:41.259Z", "modified": "2024-01-16T13:48:43.135Z"}, {"entity": "publication", "iuid": "ce0177b7c42141d582b314bf3611f72a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ce0177b7c42141d582b314bf3611f72a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ce0177b7c42141d582b314bf3611f72a"}}, "title": "Regulation of \u03b1-synuclein by chaperones in mammalian cells.", "authors": [{"family": "Burmann", "given": "Bj\u00f6rn M", "initials": "BM"}, {"family": "Gerez", "given": "Juan A", "initials": "JA"}, {"family": "Mate\u010dko-Burmann", "given": "Irena", "initials": "I"}, {"family": "Campioni", "given": "Silvia", "initials": "S"}, {"family": "Kumari", "given": "Pratibha", "initials": "P"}, {"family": "Ghosh", "given": "Dhiman", "initials": "D"}, {"family": "Mazur", "given": "Adam", "initials": "A"}, {"family": "Aspholm", "given": "Emelie E", "initials": "EE"}, {"family": "\u0160ulskis", "given": "Darius", "initials": "D"}, {"family": "Wawrzyniuk", "given": "Magdalena", "initials": "M"}, {"family": "Bock", "given": "Thomas", "initials": "T"}, {"family": "Schmidt", "given": "Alexander", "initials": "A"}, {"family": "R\u00fcdiger", "given": "Stefan G D", "initials": "SGD"}, {"family": "Riek", "given": "Roland", "initials": "R"}, {"family": "Hiller", "given": "Sebastian", "initials": "S"}], "type": "journal article", "published": "2020-01-00", "journal": {"title": "Nature", "issn": "1476-4687", "volume": "577", "issue": "7788", "pages": "127-132", "issn-l": "0028-0836"}, "abstract": "Neurodegeneration in patients with Parkinson's disease is correlated with the occurrence of Lewy bodies-intracellular inclusions that contain aggregates of the intrinsically disordered protein \u03b1-synuclein1. The aggregation propensity of \u03b1-synuclein in cells is modulated by specific factors that include post-translational modifications2,3, Abelson-kinase-mediated phosphorylation4,5 and interactions with intracellular machineries such as molecular chaperones, although the underlying mechanisms are unclear6-8. Here we systematically characterize the interaction of molecular chaperones with \u03b1-synuclein in vitro as well as in cells at the atomic level. We find that six highly divergent molecular chaperones commonly recognize a canonical motif in \u03b1-synuclein, consisting of the N terminus and a segment around Tyr39, and hinder the aggregation of \u03b1-synuclein. NMR experiments9 in cells show that the same transient interaction pattern is preserved inside living mammalian cells. Specific inhibition of the interactions between \u03b1-synuclein and the chaperone HSC70 and members of the HSP90 family, including HSP90\u03b2, results in transient membrane binding and triggers a remarkable re-localization of \u03b1-synuclein to the mitochondria and concomitant formation of aggregates. Phosphorylation of \u03b1-synuclein at Tyr39 directly impairs the interaction of \u03b1-synuclein with chaperones, thus providing a functional explanation for the role of Abelson kinase in Parkinson's disease. Our results establish a master regulatory mechanism of \u03b1-synuclein function and aggregation in mammalian cells, extending the functional repertoire of molecular chaperones and highlighting new perspectives for therapeutic interventions for Parkinson's disease.", "doi": "10.1038/s41586-019-1808-9", "pmid": "31802003", "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41586-019-1808-9"}, {"db": "pmc", "key": "PMC6930850"}, {"db": "mid", "key": "EMS84680"}], "notes": [], "created": "2020-01-07T11:00:49.664Z", "modified": "2025-10-17T13:03:57.242Z"}, {"entity": "publication", "iuid": "5eb47205592b4eb78cfff50bb2fde093", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5eb47205592b4eb78cfff50bb2fde093.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5eb47205592b4eb78cfff50bb2fde093"}}, "title": "Protein and DNA methylation-based scores as surrogate markers for interferon system activation in patients with primary Sj\u00f6gren's syndrome.", "authors": [{"family": "Bj\u00f6rk", "given": "Albin", "initials": "A"}, {"family": "Richardsdotter Andersson", "given": "Elina", "initials": "E"}, {"family": "Imgenberg-Kreuz", "given": "Juliana", "initials": "J"}, {"family": "Thorlacius", "given": "Gudny Ella", "initials": "GE"}, {"family": "Mofors", "given": "Johannes", "initials": "J"}, {"family": "Syv\u00e4nen", "given": "Ann-Christine", "initials": "AC", "orcid": "0000-0002-9681-9146", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7012e35025543379380cb90efd71243.json"}}, {"family": "Kvarnstr\u00f6m", "given": "Marika", "initials": "M"}, {"family": "Nordmark", "given": "Gunnel", "initials": "G", "orcid": "0000-0002-3829-7431", "researcher": {"href": "https://publications.scilifelab.se/researcher/188fda53498740dbb007441cc94bb1ad.json"}}, {"family": "Wahren-Herlenius", "given": "Marie", "initials": "M", "orcid": "0000-0002-0915-7245", "researcher": {"href": "https://publications.scilifelab.se/researcher/a8451e7f5e6e4e4da0bace3dfafaeb38.json"}}], "type": "journal article", "published": "2020-01-00", "journal": {"title": "RMD Open", "issn": "2056-5933", "issn-l": "2056-5933", "volume": "6", "issue": "1", "pages": "e000995"}, "abstract": "Standard assessment of interferon (IFN) system activity in systemic rheumatic diseases depends on the availability of RNA samples. In this study, we describe and evaluate alternative methods using plasma, serum and DNA samples, exemplified in the IFN-driven disease primary Sj\u00f6gren's syndrome (pSS).\n\nPatients with pSS seropositive or negative for anti-SSA/SSB and controls were included. Protein-based IFN (pIFN) scores were calculated from levels of PD-1, CXCL9 and CXCL10. DNA methylation-based (DNAm) IFN scores were calculated from DNAm levels at RSAD2, IFIT1 and IFI44L . Scores were compared with mRNA-based IFN scores measured by quantitative PCR (qPCR), Nanostring or RNA sequencing (RNAseq).\n\nmRNA-based IFN scores displayed strong correlations between B cells and monocytes (r=0.93 and 0.95, p<0.0001) and between qPCR and Nanostring measurements (r=0.92 and 0.92, p<0.0001). The pIFN score in plasma and serum was higher in patients compared with controls (p<0.0001) and correlated well with mRNA-based IFN scores (r=0.62-0.79, p<0.0001), as well as with each other (r=0.94, p<0.0001). Concordance of classification as 'high' or 'low' IFN signature between the pIFN score and mRNA-based IFN scores ranged from 79.5% to 88.6%, and the pIFN score was effective at classifying patients and controls (area under the curve, AUC=0.89-0.93, p<0.0001). The DNAm IFN score showed strong correlation to the RNAseq IFN score (r=0.84, p<0.0001) and performed well in classifying patients and controls (AUC=0.96, p<0.0001).\n\nWe describe novel methods of assessing IFN system activity in plasma, serum or DNA samples, which may prove particularly valuable in studies where RNA samples are not available.", "doi": "10.1136/rmdopen-2019-000995", "pmid": "31958277", "labels": {"National Genomics Infrastructure": "Service", "Clinical Biomarkers": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "PLA and Single Cell Proteomics": "Service", "Affinity Proteomics Uppsala": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "rmdopen-2019-000995"}, {"db": "pmc", "key": "PMC7046975"}], "notes": [], "created": "2020-01-23T16:05:43.255Z", "modified": "2024-01-16T13:48:43.143Z"}, {"entity": "publication", "iuid": "e183de5687764f018052867552a12eef", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e183de5687764f018052867552a12eef.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e183de5687764f018052867552a12eef"}}, "title": "Probabilistic cell typing enables fine mapping of closely related cell types in situ.", "authors": [{"family": "Qian", "given": "Xiaoyan", "initials": "X", "orcid": "0000-0001-7509-8071", "researcher": {"href": "https://publications.scilifelab.se/researcher/835743f43787492498e3c610184cf9a3.json"}}, {"family": "Harris", "given": "Kenneth D", "initials": "KD", "orcid": "0000-0002-5930-6456", "researcher": {"href": "https://publications.scilifelab.se/researcher/8d82ff0750e140a2820eb51c19eb9437.json"}}, {"family": "Hauling", "given": "Thomas", "initials": "T"}, {"family": "Nicoloutsopoulos", "given": "Dimitris", "initials": "D"}, {"family": "Mu\u00f1oz-Manchado", "given": "Ana B", "initials": "AB"}, {"family": "Skene", "given": "Nathan", "initials": "N", "orcid": "0000-0002-6807-3180", "researcher": {"href": "https://publications.scilifelab.se/researcher/0b4340cc0fa948eda26ce5618ebc0693.json"}}, {"family": "Hjerling-Leffler", "given": "Jens", "initials": "J", "orcid": "0000-0002-4539-1776", "researcher": {"href": "https://publications.scilifelab.se/researcher/51675f0ff9aa47d89d6b2eb84a14820a.json"}}, {"family": "Nilsson", "given": "Mats", "initials": "M", "orcid": "0000-0001-9985-0387", "researcher": {"href": "https://publications.scilifelab.se/researcher/197cf8ba83ba430f9712b2f4d94dc3e5.json"}}], "type": "journal article", "published": "2020-01-00", "journal": {"title": "Nat. Methods", "issn": "1548-7105", "issn-l": "1548-7091", "volume": "17", "issue": "1", "pages": "101-106"}, "abstract": "Understanding the function of a tissue requires knowing the spatial organization of its constituent cell types. In the cerebral cortex, single-cell RNA sequencing (scRNA-seq) has revealed the genome-wide expression patterns that define its many, closely related neuronal types, but cannot reveal their spatial arrangement. Here we introduce probabilistic cell typing by in situ sequencing (pciSeq), an approach that leverages previous scRNA-seq classification to identify cell types using multiplexed in situ RNA detection. We applied this method by mapping the inhibitory neurons of mouse hippocampal area CA1, for which ground truth is available from extensive previous work identifying their laminar organization. Our method identified these neuronal classes in a spatial arrangement matching ground truth, and further identified multiple classes of isocortical pyramidal cell in a pattern matching their known organization. This method will allow identifying the spatial organization of closely related cell types across the brain and other tissues.", "doi": "10.1038/s41592-019-0631-4", "pmid": "31740815", "labels": {"Bioinformatics Support for Computational Resources": "Service", "In Situ Sequencing": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41592-019-0631-4"}, {"db": "pmc", "key": "PMC6949128"}, {"db": "mid", "key": "EMS84576"}], "notes": [], "created": "2020-01-10T04:54:58.127Z", "modified": "2025-10-17T13:02:18.185Z"}, {"entity": "publication", "iuid": "c6df05498a44432f99bdc64a2038a4ab", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c6df05498a44432f99bdc64a2038a4ab.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c6df05498a44432f99bdc64a2038a4ab"}}, "title": "NMR Spectroscopic Analysis to Evaluate the Quality of Insulin: Concentration, Variability, and Excipient Content.", "authors": [{"family": "Malmodin", "given": "Daniel", "initials": "D"}, {"family": "Pedersen", "given": "Anders", "initials": "A", "orcid": "0000-0001-8704-5129", "researcher": {"href": "https://publications.scilifelab.se/researcher/c01eb312c2a0478da73e5f12d84658da.json"}}, {"family": "Karlsson", "given": "B G\u00f6ran", "initials": "BG"}, {"family": "Forsander", "given": "Gun", "initials": "G"}], "type": "journal article", "published": "2020-01-00", "journal": {"title": "J Diabetes Sci Technol", "issn": "1932-2968", "volume": "14", "issue": "1", "pages": "180-184", "issn-l": null}, "abstract": "Known and consistent bioactivity between samples of insulin is essential to correctly estimate the dose. Insulin concentration is not the same thing as bioactivity, however, and methods to correctly determine both are required. Here we show that one dimensional nuclear magnetic resonance (1D NMR), in contrast to, for example, reverse phase high pressure liquid chromatography, can be used to determine both insulin concentration as well as confirm the structural integrity required for activity. In response to the report by Carter and Heinemann, we decided to investigate insulin intended for public use. Insulin from several manufacturers was investigated. Correct insulin concentrations were found in all tested samples although the general sample variability, which possibly could influence the bioactivity, varied depending on insulin type and manufacturer.", "doi": "10.1177/1932296819831995", "pmid": "30782004", "labels": {"Swedish NMR Centre": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC7189154"}], "notes": [], "created": "2020-01-07T11:43:48.593Z", "modified": "2025-10-17T13:03:57.252Z"}, {"entity": "publication", "iuid": "7cb0012083b14d21a8283ff379002b6d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7cb0012083b14d21a8283ff379002b6d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7cb0012083b14d21a8283ff379002b6d"}}, "title": "NIST Interlaboratory Study on Glycosylation Analysis of Monoclonal Antibodies: Comparison of Results from Diverse Analytical Methods.", "authors": [{"family": "De Leoz", "given": "Maria Lorna A", "initials": "MLA"}, {"family": "Duewer", "given": "David L", "initials": "DL", "orcid": "0000-0002-3924-3064", "researcher": {"href": "https://publications.scilifelab.se/researcher/99b4df16309e4d2dbaa8d9bf3df820f2.json"}}, {"family": "Fung", "given": "Adam", "initials": "A"}, {"family": "Liu", "given": "Lily", "initials": "L"}, {"family": "Yau", "given": "Hoi Kei", "initials": "HK"}, {"family": "Potter", "given": "Oscar", "initials": "O"}, {"family": "Staples", "given": "Gregory O", "initials": "GO"}, {"family": "Furuki", "given": "Kenichiro", "initials": "K"}, {"family": "Frenkel", "given": "Ruth", "initials": "R"}, {"family": "Hu", "given": "Yunli", "initials": "Y"}, {"family": "Sosic", "given": "Zoran", "initials": "Z"}, {"family": "Zhang", "given": "Peiqing", "initials": "P"}, {"family": "Altmann", "given": "Friedrich", "initials": "F", "orcid": "0000-0002-0112-7877", "researcher": {"href": "https://publications.scilifelab.se/researcher/16d364b528014f9596c4dfd5c67ff083.json"}}, {"family": "Grunwald-Grube", "given": "Clemens", "initials": "C"}, {"family": "Shao", "given": "Chun", "initials": "C"}, {"family": "Zaia", "given": "Joseph", "initials": "J", "orcid": "0000-0001-9497-8701", "researcher": {"href": "https://publications.scilifelab.se/researcher/cbd37a96b72b413db6f6bc489fb1acfe.json"}}, {"family": "Evers", "given": "Waltraud", "initials": "W"}, {"family": "Pengelley", "given": "Stuart", "initials": "S"}, {"family": "Suckau", "given": "Detlev", "initials": "D"}, {"family": "Wiechmann", "given": "Anja", "initials": "A"}, {"family": "Resemann", "given": "Anja", "initials": "A"}, {"family": "Jabs", "given": "Wolfgang", "initials": "W"}, {"family": "Beck", "given": "Alain", "initials": "A"}, {"family": "Froehlich", "given": "John W", "initials": "JW", "orcid": "0000-0002-5354-5632", "researcher": {"href": "https://publications.scilifelab.se/researcher/15d7f38e173d46a79f079808ebd8ac34.json"}}, {"family": "Huang", "given": "Chuncui", "initials": "C"}, {"family": "Li", "given": "Yan", "initials": "Y"}, {"family": "Liu", "given": "Yaming", "initials": "Y"}, {"family": "Sun", "given": "Shiwei", "initials": "S"}, {"family": "Wang", "given": "Yaojun", "initials": "Y"}, {"family": "Seo", "given": "Youngsuk", "initials": "Y"}, {"family": "An", "given": "Hyun Joo", "initials": "HJ"}, {"family": "Reichardt", "given": "Niels-Christian", "initials": "NC"}, {"family": "Ruiz", "given": "Juan Echevarria", "initials": "JE"}, {"family": "Archer-Hartmann", "given": "Stephanie", "initials": "S"}, {"family": "Azadi", "given": "Parastoo", "initials": "P"}, {"family": "Bell", "given": "Len", "initials": "L"}, {"family": "Lakos", "given": "Zsuzsanna", "initials": "Z"}, {"family": "An", "given": "Yanming", "initials": "Y"}, {"family": "Cipollo", "given": "John F", "initials": "JF"}, {"family": "Pucic-Bakovic", "given": "Maja", "initials": "M"}, {"family": "\u0160tambuk", "given": "Jerko", "initials": "J"}, {"family": "Lauc", "given": "Gordan", "initials": "G", "orcid": "0000-0003-1840-9560", "researcher": {"href": "https://publications.scilifelab.se/researcher/940da6ba446a40259bb53df8f7b08e3b.json"}}, {"family": "Li", "given": "Xu", "initials": "X"}, {"family": "Wang", "given": "Peng George", "initials": "PG", "orcid": "0000-0003-3335-6794", "researcher": {"href": "https://publications.scilifelab.se/researcher/091d7f6c62af4a329646b88e2a679d6a.json"}}, {"family": "Bock", "given": "Andreas", "initials": "A"}, {"family": "Hennig", "given": "Ren\u00e9", "initials": "R"}, {"family": "Rapp", "given": "Erdmann", "initials": "E"}, {"family": "Creskey", "given": "Marybeth", "initials": "M"}, {"family": "Cyr", "given": "Terry D", "initials": "TD"}, {"family": "Nakano", "given": "Miyako", "initials": "M"}, {"family": "Sugiyama", "given": "Taiki", "initials": "T"}, {"family": "Leung", "given": "Pui-King Amy", "initials": "PA"}, {"family": "Link-Lenczowski", "given": "Pawe\u0142", "initials": "P"}, {"family": "Jaworek", "given": "Jolanta", "initials": "J"}, {"family": "Yang", "given": "Shuang", "initials": "S"}, {"family": "Zhang", "given": "Hui", "initials": "H"}, {"family": "Kelly", "given": "Tim", "initials": "T"}, {"family": "Klapoetke", "given": "Song", "initials": "S"}, {"family": "Cao", "given": "Rui", "initials": "R"}, {"family": "Kim", "given": "Jin Young", "initials": "JY"}, {"family": "Lee", "given": "Hyun Kyoung", "initials": "HK"}, {"family": "Lee", "given": "Ju Yeon", "initials": "JY"}, {"family": "Yoo", "given": "Jong Shin", "initials": "JS"}, {"family": "Kim", "given": "Sa-Rang", "initials": "SR"}, {"family": "Suh", "given": "Soo-Kyung", "initials": "SK"}, {"family": "de Haan", "given": "Noortje", "initials": "N"}, {"family": "Falck", "given": "David", "initials": "D"}, {"family": "Lageveen-Kammeijer", "given": "Guinevere S M", "initials": "GSM"}, {"family": "Wuhrer", "given": "Manfred", "initials": "M", "orcid": "0000-0002-0814-4995", "researcher": {"href": "https://publications.scilifelab.se/researcher/5ab19881184f4b56b6be4fa51b8f2815.json"}}, {"family": "Emery", "given": "Robert J", "initials": "RJ"}, {"family": "Kozak", "given": "Radoslaw P", "initials": "RP"}, {"family": "Liew", "given": "Li Phing", "initials": "LP"}, {"family": "Royle", "given": "Louise", "initials": "L"}, {"family": "Urbanowicz", "given": "Paulina A", "initials": "PA"}, {"family": "Packer", "given": "Nicolle H", "initials": "NH", "orcid": "0000-0002-7532-4021", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d335a114587477bbb7456c0c5c71a32.json"}}, {"family": "Song", "given": "Xiaomin", "initials": "X"}, {"family": "Everest-Dass", "given": "Arun", "initials": "A"}, {"family": "Lattov\u00e1", "given": "Erika", "initials": "E"}, {"family": "Cajic", "given": "Samanta", "initials": "S"}, {"family": "Alagesan", "given": "Kathirvel", "initials": "K"}, {"family": "Kolarich", "given": "Daniel", "initials": "D", "orcid": "0000-0002-8452-1350", "researcher": {"href": "https://publications.scilifelab.se/researcher/5917c5d7845642d4a20ea05e52f70706.json"}}, {"family": "Kasali", "given": "Toyin", "initials": "T"}, {"family": "Lindo", "given": "Viv", "initials": "V"}, {"family": "Chen", "given": "Yuetian", "initials": "Y"}, {"family": "Goswami", "given": "Kudrat", "initials": "K"}, {"family": "Gau", "given": "Brian", "initials": "B"}, {"family": "Amunugama", "given": "Ravi", "initials": "R"}, {"family": "Jones", "given": "Richard", "initials": "R"}, {"family": "Stroop", "given": "Corn\u00e9 J M", "initials": "CJM"}, {"family": "Kato", "given": "Koichi", "initials": "K"}, {"family": "Yagi", "given": "Hirokazu", "initials": "H", "orcid": "0000-0001-9296-0225", "researcher": {"href": "https://publications.scilifelab.se/researcher/dcb01dff390e4a9fb2a37f86da8d1052.json"}}, {"family": "Kondo", "given": "Sachiko", "initials": "S"}, {"family": "Yuen", "given": "C T", "initials": "CT"}, {"family": "Harazono", "given": "Akira", "initials": "A"}, {"family": "Shi", "given": "Xiaofeng", "initials": "X"}, {"family": "Magnelli", "given": "Paula E", "initials": "PE"}, {"family": "Kasper", "given": "Brian T", "initials": "BT"}, {"family": "Mahal", "given": "Lara", "initials": "L", "orcid": "0000-0003-4791-8524", "researcher": {"href": "https://publications.scilifelab.se/researcher/ad774c07489a4ccf9ca7aa608a3ac7d1.json"}}, {"family": "Harvey", "given": "David J", "initials": "DJ"}, {"family": "O'Flaherty", "given": "Roisin", "initials": "R", "orcid": "0000-0003-1941-4775", "researcher": {"href": "https://publications.scilifelab.se/researcher/72faaf761a604987bfb1b3e9538885aa.json"}}, {"family": "Rudd", "given": "Pauline M", "initials": "PM"}, {"family": "Saldova", "given": "Radka", "initials": "R", "orcid": "0000-0001-5085-5080", "researcher": {"href": "https://publications.scilifelab.se/researcher/878da0e7f823400a9e6fd54668e1c863.json"}}, {"family": "Hecht", "given": "Elizabeth S", "initials": "ES"}, {"family": "Muddiman", "given": "David C", "initials": "DC"}, {"family": "Kang", "given": "Jichao", "initials": "J"}, {"family": "Bhoskar", "given": "Prachi", "initials": "P"}, {"family": "Menard", "given": "Daniele", "initials": "D"}, {"family": "Saati", "given": "Andrew", "initials": "A"}, {"family": "Merle", "given": "Christine", "initials": "C"}, {"family": "Mast", "given": "Steven", "initials": "S"}, {"family": "Tep", "given": "Sam", "initials": "S"}, {"family": "Truong", "given": "Jennie", "initials": "J"}, {"family": "Nishikaze", "given": "Takashi", "initials": "T"}, {"family": "Sekiya", "given": "Sadanori", "initials": "S"}, {"family": "Shafer", "given": "Aaron", "initials": "A"}, {"family": "Funaoka", "given": "Sohei", "initials": "S"}, {"family": "Toyoda", "given": "Masaaki", "initials": "M"}, {"family": "de Vreugd", "given": "Peter", "initials": "P"}, {"family": "Caron", "given": "Cassie", "initials": "C"}, {"family": "Pradhan", "given": "Pralima", "initials": "P"}, {"family": "Tan", "given": "Niclas Chiang", "initials": "NC"}, {"family": "Mechref", "given": "Yehia", "initials": "Y", "orcid": "0000-0002-6661-6073", "researcher": {"href": "https://publications.scilifelab.se/researcher/3c69b68a57044d318b148ac177e90c95.json"}}, {"family": "Patil", "given": "Sachin", "initials": "S"}, {"family": "Rohrer", "given": "Jeffrey S", "initials": "JS"}, {"family": "Chakrabarti", "given": "Ranjan", "initials": "R"}, {"family": "Dadke", "given": "Disha", "initials": "D"}, {"family": "Lahori", "given": "Mohammedazam", "initials": "M"}, {"family": "Zou", "given": "Chunxia", "initials": "C"}, {"family": "Cairo", "given": "Christopher", "initials": "C", "orcid": "0000-0003-3363-8708", "researcher": {"href": "https://publications.scilifelab.se/researcher/431e10a4460f4bf28986b07c7d33e1c3.json"}}, {"family": "Reiz", "given": "B\u00e9la", "initials": "B"}, {"family": "Whittal", "given": "Randy M", "initials": "RM"}, {"family": "Lebrilla", "given": "Carlito B", "initials": "CB", "orcid": "0000-0001-7190-5323", "researcher": {"href": "https://publications.scilifelab.se/researcher/f946685a56074613a29172f91a067860.json"}}, {"family": "Wu", "given": "Lauren", "initials": "L"}, {"family": "Guttman", "given": "Andras", "initials": "A"}, {"family": "Szigeti", "given": "Marton", "initials": "M"}, {"family": "Kremkow", "given": "Benjamin G", "initials": "BG"}, {"family": "Lee", "given": "Kelvin H", "initials": "KH"}, {"family": "Sihlbom", "given": "Carina", "initials": "C"}, {"family": "Adamczyk", "given": "Barbara", "initials": "B"}, {"family": "Jin", "given": "Chunsheng", "initials": "C", "orcid": "0000-0002-0229-102X", "researcher": {"href": "https://publications.scilifelab.se/researcher/458804f3f7274b8a9efe7a90469d0e56.json"}}, {"family": "Karlsson", "given": "Niclas G", "initials": "NG", "orcid": "0000-0002-3045-2628", "researcher": {"href": "https://publications.scilifelab.se/researcher/62e0b7440ff1447c9611d938d185fbc7.json"}}, {"family": "\u00d6rnros", "given": "Jessica", "initials": "J"}, {"family": "Larson", "given": "G\u00f6ran", "initials": "G", "orcid": "0000-0002-2616-0366", "researcher": {"href": "https://publications.scilifelab.se/researcher/62a940eae9164c56a1d2f9b8ef8242cd.json"}}, {"family": "Nilsson", "given": "Jonas", "initials": "J"}, {"family": "Meyer", "given": "Bernd", "initials": "B"}, {"family": "Wiegandt", "given": "Alena", "initials": "A"}, {"family": "Komatsu", "given": "Emy", "initials": "E"}, {"family": "Perreault", "given": "Helene", "initials": "H"}, {"family": "Bodnar", "given": "Edward D", "initials": "ED"}, {"family": "Said", "given": "Nassur", "initials": "N"}, {"family": "Francois", "given": "Yannis-Nicolas", "initials": "YN"}, {"family": "Leize-Wagner", "given": "Emmanuelle", "initials": "E"}, {"family": "Maier", "given": "Sandra", "initials": "S"}, {"family": "Zeck", "given": "Anne", "initials": "A"}, {"family": "Heck", "given": "Albert J R", "initials": "AJR", "orcid": "0000-0002-2405-4404", "researcher": {"href": "https://publications.scilifelab.se/researcher/ecb05632b366409da1c6a8395e2f5050.json"}}, {"family": "Yang", "given": "Yang", "initials": "Y"}, {"family": "Haselberg", "given": "Rob", "initials": "R"}, {"family": "Yu", "given": "Ying Qing", "initials": "YQ"}, {"family": "Alley", "given": "William", "initials": "W"}, {"family": "Leone", "given": "Joseph W", "initials": "JW"}, {"family": "Yuan", "given": "Hua", "initials": "H"}, {"family": "Stein", "given": "Stephen E", "initials": "SE"}], "type": "journal article", "published": "2020-01-00", "journal": {"volume": "19", "issn": "1535-9484", "issue": "1", "pages": "11-30", "title": "Mol. Cell Proteomics", "issn-l": "1535-9476"}, "abstract": "Glycosylation is a topic of intense current interest in the development of biopharmaceuticals because it is related to drug safety and efficacy. This work describes results of an interlaboratory study on the glycosylation of the Primary Sample (PS) of NISTmAb, a monoclonal antibody reference material. Seventy-six laboratories from industry, university, research, government, and hospital sectors in Europe, North America, Asia, and Australia submitted a total of 103 reports on glycan distributions. The principal objective of this study was to report and compare results for the full range of analytical methods presently used in the glycosylation analysis of mAbs. Therefore, participation was unrestricted, with laboratories choosing their own measurement techniques. Protein glycosylation was determined in various ways, including at the level of intact mAb, protein fragments, glycopeptides, or released glycans, using a wide variety of methods for derivatization, separation, identification, and quantification. Consequently, the diversity of results was enormous, with the number of glycan compositions identified by each laboratory ranging from 4 to 48. In total, one hundred sixteen glycan compositions were reported, of which 57 compositions could be assigned consensus abundance values. These consensus medians provide community-derived values for NISTmAb PS. Agreement with the consensus medians did not depend on the specific method or laboratory type. The study provides a view of the current state-of-the-art for biologic glycosylation measurement and suggests a clear need for harmonization of glycosylation analysis methods.", "doi": "10.1074/mcp.RA119.001677", "pmid": "31591262", "labels": {"Glycoproteomics and MS Proteomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC6944243"}, {"db": "pii", "key": "S1535-9476(20)30003-7"}], "notes": [], "created": "2020-01-27T21:30:45.065Z", "modified": "2024-01-16T13:46:31.008Z"}, {"entity": "publication", "iuid": "8d9a5bdc18694364a23ff3b134f7e069", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8d9a5bdc18694364a23ff3b134f7e069.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8d9a5bdc18694364a23ff3b134f7e069"}}, "title": "Molecular mechanisms of collateral sensitivity to the antibiotic nitrofurantoin.", "authors": [{"family": "Roemhild", "given": "Roderich", "initials": "R", "orcid": "0000-0001-9480-5261", "researcher": {"href": "https://publications.scilifelab.se/researcher/817ce0f8274f4a8d88867af5b4dad172.json"}}, {"family": "Linkevicius", "given": "Marius", "initials": "M", "orcid": "0000-0001-5760-2721", "researcher": {"href": "https://publications.scilifelab.se/researcher/a3ef4e2dd7fa44bb91db1d4a5b855d72.json"}}, {"family": "Andersson", "given": "Dan I", "initials": "DI", "orcid": "0000-0001-6640-2174", "researcher": {"href": "https://publications.scilifelab.se/researcher/fb042b3dfa21450e862a29951ea0c1eb.json"}}], "type": "journal article", "published": "2020-01-00", "journal": {"title": "PLoS Biol.", "issn": "1545-7885", "volume": "18", "issue": "1", "pages": "e3000612", "issn-l": "1544-9173"}, "abstract": "Antibiotic resistance increasingly limits the success of antibiotic treatments, and physicians require new ways to achieve efficient treatment despite resistance. Resistance mechanisms against a specific antibiotic class frequently confer increased susceptibility to other antibiotic classes, a phenomenon designated collateral sensitivity (CS). An informed switch of antibiotic may thus enable the efficient treatment of resistant strains. CS occurs in many pathogens, but the mechanisms that generate hypersusceptibility are largely unknown. We identified several molecular mechanisms of CS against the antibiotic nitrofurantoin (NIT). Mutants that are resistant against tigecycline (tetracycline), mecillinam (\u03b2-lactam), and protamine (antimicrobial peptide) all show CS against NIT. Their hypersusceptibility is explained by the overexpression of nitroreductase enzymes combined with increased drug uptake rates, or increased drug toxicity. Increased toxicity occurs through interference of the native drug-response system for NIT, the SOS response, with growth. A mechanistic understanding of CS will help to develop drug switches that combat resistance.", "doi": "10.1371/journal.pbio.3000612", "pmid": "31986134", "labels": {"Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [{"db": "pii", "key": "PBIOLOGY-D-19-02723"}, {"db": "pmc", "key": "PMC7004380"}], "notes": [], "created": "2020-01-30T15:58:40.458Z", "modified": "2024-01-16T13:46:31.019Z"}, {"entity": "publication", "iuid": "d239168bc91848948c62f51ca1b24557", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d239168bc91848948c62f51ca1b24557.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d239168bc91848948c62f51ca1b24557"}}, "title": "Metabolic response patterns in brain microdialysis fluids and serum during interstitial cisplatin treatment of high-grade glioma.", "authors": [{"family": "Bj\u00f6rkblom", "given": "Benny", "initials": "B", "orcid": "0000-0001-9347-5790", "researcher": {"href": "https://publications.scilifelab.se/researcher/acf29b039dfc496fb33c0cf7cb1d587c.json"}}, {"family": "Jonsson", "given": "P\u00e4r", "initials": "P"}, {"family": "Tabatabaei", "given": "Pedram", "initials": "P"}, {"family": "Bergstr\u00f6m", "given": "Per", "initials": "P"}, {"family": "Johansson", "given": "Mikael", "initials": "M"}, {"family": "Asklund", "given": "Thomas", "initials": "T"}, {"family": "Bergenheim", "given": "A Tommy", "initials": "AT"}, {"family": "Antti", "given": "Henrik", "initials": "H"}], "type": "journal article", "published": "2020-01-00", "journal": {"title": "Br. J. Cancer", "issn": "1532-1827", "volume": "122", "issue": "2", "pages": "221-232", "issn-l": "0007-0920"}, "abstract": "High-grade gliomas are associated with poor prognosis. Tumour heterogeneity and invasiveness create challenges for effective treatment and use of systemically administrated drugs. Furthermore, lack of functional predictive response-assays based on drug efficacy complicates evaluation of early treatment responses.\n\nWe used microdialysis to deliver cisplatin into the tumour and to monitor levels of metabolic compounds present in the tumour and non-malignant brain tissue adjacent to tumour, before and during treatment. In parallel, we collected serum samples and used multivariate statistics to analyse the metabolic effects.\n\nWe found distinct metabolic patterns in the extracellular fluids from tumour compared to non-malignant brain tissue, including high concentrations of a wide range of amino acids, amino acid derivatives and reduced levels of monosaccharides and purine nucleosides. We found that locoregional cisplatin delivery had a strong metabolic effect at the tumour site, resulting in substantial release of glutamic acid, phosphate, and spermidine and a reduction of cysteine levels. In addition, patients with long-time survival displayed different treatment response patterns in both tumour and serum. Longer survival was associated with low tumour levels of lactic acid, glyceric acid, ketoses, creatinine and cysteine. Patients with longer survival displayed lower serum levels of ketohexoses, fatty acid methyl esters, glycerol-3-phosphate and alpha-tocopherol, while elevated phosphate levels were seen in both tumour and serum during treatment.\n\nWe highlight distinct metabolic patterns associated with high-grade tumour metabolism, and responses to cytotoxic cisplatin treatment.", "doi": "10.1038/s41416-019-0652-x", "pmid": "31819184", "labels": {"Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41416-019-0652-x"}, {"db": "pmc", "key": "PMC7052137"}], "notes": [], "created": "2020-01-21T10:14:13.920Z", "modified": "2025-10-17T13:03:16.960Z"}, {"entity": "publication", "iuid": "3ecaeb2551904ec7aeb3bf79e8763ad5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3ecaeb2551904ec7aeb3bf79e8763ad5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3ecaeb2551904ec7aeb3bf79e8763ad5"}}, "title": "Identification of novel diagnostic and prognostic biomarkers for abdominal aortic aneurysm.", "authors": [{"family": "Memon", "given": "Ashfaque A", "initials": "AA"}, {"family": "Zarrouk", "given": "Moncef", "initials": "M"}, {"family": "\u00c5gren-Witteschus", "given": "Sophia", "initials": "S"}, {"family": "Sundquist", "given": "Jan", "initials": "J"}, {"family": "Gotts\u00e4ter", "given": "Anders", "initials": "A"}, {"family": "Sundquist", "given": "Kristina", "initials": "K"}], "type": "journal article", "published": "2020-01-00", "journal": {"title": "Eur J Prev Cardiol", "issn": "2047-4881", "issn-l": "2047-4873", "volume": "27", "issue": "2", "pages": "132-142"}, "abstract": "Abdominal aortic aneurysm is a life-threatening condition due to the risk of aneurysm growth and rupture. There are no approved diagnostic or prognostic biomarkers for abdominal aortic aneurysm. We aimed to identify diagnostic and prognostic biomarkers for abdominal aortic aneurysm and to investigate their relationship with abdominal aortic aneurysm diameter and growth.\n\nIn this case-control study, patients were included from an abdominal aortic aneurysm screening study on men aged \u226565 years. Of 24,589 examined men, 415 had abdominal aortic aneurysm, out of whom 134 consented to participate in the present study. One hundred and thirty-six screened men with aortic diameter <30 mm, matched for comorbidities and time of sampling were included as non-abdominal aortic aneurysm patients. Ninety-one cardiovascular specific proteins in plasma samples were measured by the Proseek Multiplex CVD III96x96 panel.\n\nAfter Bonferroni correction, plasma levels of 21 proteins associated with proteolysis, oxidative-stress, lipid metabolism, and inflammation were significantly increased, whereas levels of paraoxonase 3, associated with high-density lipoprotein metabolism, were decreased in abdominal aortic aneurysm patients. Combination of growth/differentiation factor 15 and cystatin B had the best ability to discriminate abdominal aortic aneurysm from non-abdominal aortic aneurysm (area under the curve, 0.76; sensitivity, 80% and specificity, 52%). Myeloperoxidase showed the best prognostic value (area under the curve, 0.71; sensitivity, 80% and specificity, 59%) and higher baseline levels of myeloperoxidase were significantly associated with faster abdominal aortic aneurysm growth compared with lower levels, independent of baseline diameter.\n\nWe have identified multiple proteins associated with abdominal aortic aneurysm diameter and growth with a potential to become novel diagnostic and prognostic biomarkers for abdominal aortic aneurysm.", "doi": "10.1177/2047487319873062", "pmid": "31466471", "labels": {"Clinical Biomarkers": "Service", "PLA and Single Cell Proteomics": "Service", "Affinity Proteomics Uppsala": "Service"}, "xrefs": [], "notes": [], "created": "2020-01-23T16:04:36.167Z", "modified": "2023-04-14T13:55:53.594Z"}, {"entity": "publication", "iuid": "35ee67ba38754d2e8cf529e8a42afa25", "links": {"self": {"href": "https://publications.scilifelab.se/publication/35ee67ba38754d2e8cf529e8a42afa25.json"}, "display": {"href": "https://publications.scilifelab.se/publication/35ee67ba38754d2e8cf529e8a42afa25"}}, "title": "IDDomainSpotter: Compositional bias reveals domains in long disordered protein regions-Insights from transcription factors.", "authors": [{"family": "Millard", "given": "Peter S", "initials": "PS", "orcid": "0000-0003-1975-952X", "researcher": {"href": "https://publications.scilifelab.se/researcher/2727f453eb524fea9fcdc0c8c3d1fe2b.json"}}, {"family": "Bugge", "given": "Katrine", "initials": "K", "orcid": "0000-0002-6286-6243", "researcher": {"href": "https://publications.scilifelab.se/researcher/abb2ffb2565b43a9b2d4a891575eb611.json"}}, {"family": "Marabini", "given": "Riccardo", "initials": "R", "orcid": "0000-0003-3929-0490", "researcher": {"href": "https://publications.scilifelab.se/researcher/ff6849b36a26415ea6b135100d349fc8.json"}}, {"family": "Boomsma", "given": "Wouter", "initials": "W", "orcid": "0000-0002-8257-3827", "researcher": {"href": "https://publications.scilifelab.se/researcher/3c4fffa2a63147d49079213a8c68e7ed.json"}}, {"family": "Burow", "given": "Meike", "initials": "M", "orcid": "0000-0002-2350-985X", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ac8209b3add4a779776052508bc1896.json"}}, {"family": "Kragelund", "given": "Birthe B", "initials": "BB", "orcid": "0000-0002-7454-1761", "researcher": {"href": "https://publications.scilifelab.se/researcher/03962568e1a945968c337cfe46e6c545.json"}}], "type": "journal article", "published": "2020-01-00", "journal": {"title": "Protein Sci.", "issn": "1469-896X", "volume": "29", "issue": "1", "pages": "169-183", "issn-l": "0961-8368"}, "abstract": "Protein domains constitute regions of distinct structural properties and molecular functions that are retained when removed from the rest of the protein. However, due to the lack of tertiary structure, the identification of domains has been largely neglected for long (>50 residues) intrinsically disordered regions. Here we present a sequence-based approach to assess and visualize domain organization in long intrinsically disordered regions based on compositional sequence biases. An online tool to find putative intrinsically disordered domains (IDDomainSpotter) in any protein sequence or sequence alignment using any particular sequence trait is available at http://www.bio.ku.dk/sbinlab/IDDomainSpotter. Using this tool, we have identified a putative domain enriched in hydrophilic and disorder-promoting residues (Pro, Ser, and Thr) and depleted in positive charges (Arg and Lys) bordering the folded DNA-binding domains of several transcription factors (p53, GCR, NAC46, MYB28, and MYB29). This domain, from two different MYB transcription factors, was characterized biophysically to determine its properties. Our analyses show the domain to be extended, dynamic and highly disordered. It connects the DNA-binding domain to other disordered domains and is present and conserved in several transcription factors from different families and domains of life. This example illustrates the potential of IDDomainSpotter to predict, from sequence alone, putative domains of functional interest in otherwise uncharacterized disordered proteins.", "doi": "10.1002/pro.3754", "pmid": "31642121", "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC6933863"}], "notes": [], "created": "2020-01-07T11:04:11.544Z", "modified": "2025-10-17T13:03:57.280Z"}, {"entity": "publication", "iuid": "015da46dd29a41c3a60f8fbeee7d70a0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/015da46dd29a41c3a60f8fbeee7d70a0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/015da46dd29a41c3a60f8fbeee7d70a0"}}, "title": "Genotypic variation in Norway spruce correlates to fungal communities in vegetative buds.", "authors": [{"family": "Elfstrand", "given": "Malin", "initials": "M", "orcid": "0000-0002-0214-5284", "researcher": {"href": "https://publications.scilifelab.se/researcher/2957dac173f4495a9245f0d8a9750606.json"}}, {"family": "Zhou", "given": "Linghua", "initials": "L"}, {"family": "Baison", "given": "John", "initials": "J", "orcid": "0000-0001-9919-907X", "researcher": {"href": "https://publications.scilifelab.se/researcher/800c157b25de42ddb0e334b9f9a88ff4.json"}}, {"family": "Olson", "given": "\u00c5ke", "initials": "\u00c5", "orcid": "0000-0001-8998-6096", "researcher": {"href": "https://publications.scilifelab.se/researcher/83a79139c2b94d9f97cf038e1cab8c03.json"}}, {"family": "Lund\u00e9n", "given": "Karl", "initials": "K", "orcid": "0000-0002-0817-2419", "researcher": {"href": "https://publications.scilifelab.se/researcher/538224bb2e2c4d98931015ada57bfaea.json"}}, {"family": "Karlsson", "given": "Bo", "initials": "B"}, {"family": "Wu", "given": "Harry X", "initials": "HX"}, {"family": "Stenlid", "given": "Jan", "initials": "J", "orcid": "0000-0002-5344-2094", "researcher": {"href": "https://publications.scilifelab.se/researcher/eac6fc31e38c4552a986310015fcb1b4.json"}}, {"family": "Garc\u00eda-Gil", "given": "M Rosario", "initials": "MR", "orcid": "0000-0002-6834-6708", "researcher": {"href": "https://publications.scilifelab.se/researcher/774898d2b46f44cb8475be89ecd8b79d.json"}}], "type": "journal article", "published": "2020-01-00", "journal": {"title": "Mol. Ecol.", "issn": "1365-294X", "volume": "29", "issue": "1", "pages": "199-213", "issn-l": "0962-1083"}, "abstract": "The taxonomically diverse phyllosphere fungi inhabit leaves of plants. Thus, apart from the fungi's dispersal capacities and environmental factors, the assembly of the phyllosphere community associated with a given host plant depends on factors encoded by the host's genome. The host genetic factors and their influence on the assembly of phyllosphere communities under natural conditions are poorly understood, especially in trees. Recent work indicates that Norway spruce (Picea abies) vegetative buds harbour active fungal communities, but these are hitherto largely uncharacterized. This study combines internal transcribed spacer sequencing of the fungal communities associated with dormant vegetative buds with a genome-wide association study (GWAS) in 478 unrelated Norway spruce trees. The aim was to detect host loci associated with variation in the fungal communities across the population, and to identify loci correlating with the presence of specific, latent, pathogens. The fungal communities were dominated by known Norway spruce phyllosphere endophytes and pathogens. We identified six quantitative trait loci (QTLs) associated with the relative abundance of the dominating taxa (i.e., top 1% most abundant taxa). Three additional QTLs associated with colonization by the spruce needle cast pathogen Lirula macrospora or the cherry spruce rust (Thekopsora areolata) in asymptomatic tissues were detected. The identification of the nine QTLs shows that the genetic variation in Norway spruce influences the fungal community in dormant buds and that mechanisms underlying the assembly of the communities and the colonization of latent pathogens in trees may be uncovered by combining molecular identification of fungi with GWAS.", "doi": "10.1111/mec.15314", "pmid": "31755612", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7003977"}], "notes": [], "created": "2020-02-11T18:51:03.676Z", "modified": "2021-11-10T12:55:31.521Z"}, {"entity": "publication", "iuid": "1fad0065d94b468984935c5caf4d75ee", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1fad0065d94b468984935c5caf4d75ee.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1fad0065d94b468984935c5caf4d75ee"}}, "title": "Genome-wide signatures of environmental adaptation in European aspen (Populus tremula) under current and future climate conditions.", "authors": [{"family": "Ingvarsson", "given": "P\u00e4r K", "initials": "PK", "orcid": "0000-0001-9225-7521", "researcher": {"href": "https://publications.scilifelab.se/researcher/52a2c210ff754465a69f839b40fe8312.json"}}, {"family": "Bernhardsson", "given": "Carolina", "initials": "C", "orcid": "0000-0002-3258-275X", "researcher": {"href": "https://publications.scilifelab.se/researcher/b8fce67de4e14fa68c0edadfec0de085.json"}}], "type": "journal article", "published": "2020-01-00", "journal": {"volume": "13", "issn": "1752-4571", "issue": "1", "pages": "132-142", "title": "Evol Appl", "issn-l": "1752-4571"}, "abstract": "Future climate change has been predicted to disrupt local adaptation in many perennial plants, such as forest trees, but the magnitude and location of these effects are thus far poorly understood. Here, we assess local adaptation to current climate in European aspen (Populus tremula) by using environmental association analyses to identify genetic variants associated with two representative climate variables describing current day variation in temperature and precipitation. We also analysed patterns of genetic differentiation between southern and northern populations and observe that regions of high genetic differentiation are enriched for SNPs that are significantly associated with climate. Using variants associated with climate, we examined patterns of isolation by distance and environment and used spatial modelling to predict the geographic distribution of genomic variation in response to two scenarios of future climate change. We show that climate conditions at a northern reference site will correspond to climate conditions experienced by current day populations located 4-8 latitude degrees further south. By assessing the relationship between phenotypic traits and vegetative fitness, we also demonstrate that southern populations harbour genetic variation that likely would be adaptive further north under both climate change scenarios. Current day populations at the lagging edge of the distribution in Sweden can therefore serve as sources for introducing adaptive alleles onto northern populations, but the likelihood of this largely depends on naturally occurring levels of gene flow.", "doi": "10.1111/eva.12792", "pmid": "31892948", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "EVA12792"}, {"db": "pmc", "key": "PMC6935590"}], "notes": [], "created": "2020-01-08T16:49:47.812Z", "modified": "2024-01-16T13:48:43.171Z"}, {"entity": "publication", "iuid": "cfb5f589e05e43198c7a7400c391ca16", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cfb5f589e05e43198c7a7400c391ca16.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cfb5f589e05e43198c7a7400c391ca16"}}, "title": "Do we really know who has an MGMT methylated glioma? Results of an international survey regarding use of MGMT analyses for glioma.", "authors": [{"family": "Malmstr\u00f6m", "given": "Annika", "initials": "A"}, {"family": "\u0141ysiak", "given": "Ma\u0142gorzata", "initials": "M"}, {"family": "Kristensen", "given": "Bjarne Winther", "initials": "BW"}, {"family": "Hovey", "given": "Elizabeth", "initials": "E"}, {"family": "Henriksson", "given": "Roger", "initials": "R"}, {"family": "S\u00f6derkvist", "given": "Peter", "initials": "P", "orcid": "0000-0001-9867-8706", "researcher": {"href": "https://publications.scilifelab.se/researcher/c1fc163b9a08421180f7f235af3897f4.json"}}], "type": "journal article", "published": "2020-01-00", "journal": {"title": "Neurooncol Pract", "issn": "2054-2577", "issn-l": null, "volume": "7", "issue": "1", "pages": "68-76"}, "abstract": "Glioma O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status informs clinical decision making. Worldwide different methods and cutoff levels are used, which can lead to discordant methylation results.\r\n\r\nWe conducted an international survey to clarify which methods are regularly used and why. We also explored opinions regarding international consensus on methods and cutoff.\r\n\r\nThe survey had 152 respondents from 25 countries. MGMT methylation status is determined for all glioblastomas in 37% of laboratories. The most common methods are methylation-specific polymerase chain reaction (msPCR) (37%) and pyrosequencing (34%). A method is selected for simplicity (56%), cost-effectiveness (50%), and reproducibility of results (52%). For sequencing, the number of CpG sites analyzed varies from 1-3 up to more than 16. For 50% of laboratories, the company producing the kit determines which CpG sites are examined, whereas 33% select the sites themselves. Selection of cutoff is equally distributed among a cutoff defined in the literature, by the local laboratory, or by the outside laboratory performing the analysis. This cutoff varies, reported from 1% to 30%, and in 1 laboratory tumor is determined as methylated in case of 1 methylated CpG site of 17 analyzed. Some report tumors as unmethylated or weakly vs highly methylated. An international consensus on MGMT methylation method and cutoff is warranted by 66% and 76% of respondents, respectively. The method preferred would be msPCR (45%) or pyrosequencing (42%), whereas 18% suggest next-generation sequencing.\r\n\r\nAlthough analysis of MGMT methylation status is routine, there is controversy regarding laboratory methods and cutoff level. Most respondents favor development of international consensus guidelines.", "doi": "10.1093/nop/npz039", "pmid": "32025325", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "npz039"}, {"db": "pmc", "key": "PMC6993038"}], "notes": [], "created": "2020-12-11T13:38:02.200Z", "modified": "2021-12-09T12:05:56.843Z"}, {"entity": "publication", "iuid": "4a530cc078974c2fa521cfd52618150b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4a530cc078974c2fa521cfd52618150b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4a530cc078974c2fa521cfd52618150b"}}, "title": "Developmental exposure to a human relevant mixture of endocrine disruptors alters metabolism and adipogenesis in zebrafish (Danio rerio).", "authors": [{"family": "Mentor", "given": "Anna", "initials": "A", "orcid": "0000-0002-7389-8849", "researcher": {"href": "https://publications.scilifelab.se/researcher/a9f81325ea6d49afb632bfbbeb3cdfa4.json"}}, {"family": "Brunstr\u00f6m", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Mattsson", "given": "Anna", "initials": "A", "orcid": "0000-0002-5328-6255", "researcher": {"href": "https://publications.scilifelab.se/researcher/e317be04e29a4448a0275e38dd7b0d52.json"}}, {"family": "J\u00f6nsson", "given": "Maria", "initials": "M"}], "type": "journal article", "published": "2020-01-00", "journal": {"title": "Chemosphere", "issn": "1879-1298", "volume": "238", "issue": null, "pages": "124584", "issn-l": "0045-6535"}, "abstract": "Exposure to endocrine disrupting chemicals has been suggested to contribute to the ongoing globally increasing obesity trend. The complex chemical mixtures that humans and wildlife are exposed to include a number of compounds that may have obesogenic properties. In this study we examined a mixture consisting of phthalate-monoesters, triclosan, and perfluorinated compounds. The mixture was designed within the EDC-MixRisk project based on serum levels of the compounds in pregnant women of a Swedish mother-child cohort. The compounds were negatively associated with birth weight of the children. We assessed whether developmental exposure to this mixture in combination with a calorie-rich diet affected metabolic rate, blood lipids, adipogenesis and lipid storage, and the whole-body level of neutral lipids in zebrafish (Danio rerio). Wildtype zebrafish were exposed to the mixture from 3 h post fertilization to 5, 14 or 17 days post fertilization (dpf) at water concentrations corresponding to 1, 10, 20, or 100 times the geometrical mean of the serum concentration (hsc) in the women. Exposure to the mixture at 20 times hsc lowered metabolic rate at 2-5 dpf, and increased the number of adipocytes and the amount of visceral adipose tissue at 14 and 17 dpf respectively. Also, mRNA expression of fatty acid binding protein 11a was increased at 17 dpf by 10 and 20 times hsc of the mixture. This study shows that a human-relevant mixture of environmental pollutants affects metabolic rate, adipogenesis and lipid storage in young zebrafish fed a calorie-rich diet, thus demonstrating its potential to disrupt metabolism.", "doi": "10.1016/j.chemosphere.2019.124584", "pmid": "31470313", "labels": {"Genome Engineering Zebrafish": "Service"}, "xrefs": [{"db": "pii", "key": "S0045-6535(19)31808-9"}], "notes": [], "created": "2019-12-02T13:30:04.858Z", "modified": "2021-11-10T12:55:34.802Z"}, {"entity": "publication", "iuid": "341c3e13ff774a1ca148e1a9012aa4c9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/341c3e13ff774a1ca148e1a9012aa4c9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/341c3e13ff774a1ca148e1a9012aa4c9"}}, "title": "Circadian regulation of phosphodiesterase 6 genes in zebrafish differs between cones and rods: Implications for photopic and scotopic vision.", "authors": [{"family": "Abalo", "given": "Xes\u00fas M", "initials": "XM", "orcid": "0000-0002-1643-0705", "researcher": {"href": "https://publications.scilifelab.se/researcher/944b78e930df40ee8cd5d590638cd4d9.json"}}, {"family": "Lagman", "given": "David", "initials": "D"}, {"family": "Heras", "given": "Gabriel", "initials": "G"}, {"family": "Del Pozo", "given": "Ana", "initials": "A"}, {"family": "Eggert", "given": "Joel", "initials": "J"}, {"family": "Larhammar", "given": "Dan", "initials": "D", "orcid": "0000-0002-6736-0663", "researcher": {"href": "https://publications.scilifelab.se/researcher/9e0adfcdb2cb4323a15eeaaa86541415.json"}}], "type": "journal article", "published": "2020-01-00", "journal": {"title": "Vision Res.", "issn": "1878-5646", "volume": "166", "issue": null, "pages": "43-51", "issn-l": "0042-6989"}, "abstract": "A correlation is known to exist between visual sensitivity and oscillations in red opsinand rhodopsin gene expression in zebrafish, both regulated by the clock gene. This indicates that an endogenous circadian clock regulates behavioural visual sensitivity, apart from the regulation exerted by the pineal organ. However, the specific mechanisms for cones (photopic vision) and rods (scotopic vision) are poorly understood. In this work, we performed gene expression, cosinor and immunohistochemical analyses to investigate other key genes involved in light perception, encoding the different subunits of phosphodiesterase pde6 and transducin G\u03b1T, in constant lighting conditions and compared to normal light-dark conditions. We found that cones display prominent circadian oscillations in mRNA levels for the inhibitory subunit gene pde6ha that could contribute to the regulation of photopic sensitivity by preventing overstimulation in photopic conditions. In rods, the mRNA levels of the inhibitory subunit gene pde6ga oscillate under normal conditions and dampen down in constant light but continue oscillating in constant darkness. There is an increase in total relative expression for pde6gb in constant conditions. These observations, together with previous data, suggest a complex regulation of the scotopic sensitivity involving endogenous and non-endogenous components, possibly present also in other teleost species. The G\u03b1T genes do not display mRNA oscillations and therefore may not be essential for the circadian regulation of photosensitivity. In summary, our results support different regulation for the zebrafish photopic and scotopic sensitivities and suggest circadian regulation of pde6ha as a key factor regulating photopic sensitivity, while the regulatory mechanisms in rods appear to be more complex.", "doi": "10.1016/j.visres.2019.11.001", "pmid": "31855667", "labels": {"Genome Engineering Zebrafish": "Service"}, "xrefs": [{"db": "pii", "key": "S0042-6989(19)30195-6"}], "notes": [], "created": "2020-02-07T17:12:00.207Z", "modified": "2021-11-10T12:55:35.871Z"}, {"entity": "publication", "iuid": "9a523e4820c644a7959df8ad9317e94c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9a523e4820c644a7959df8ad9317e94c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9a523e4820c644a7959df8ad9317e94c"}}, "title": "Cell-of-origin determined by both gene expression profiling and immunohistochemistry is the strongest predictor of survival in patients with diffuse large B-cell lymphoma.", "authors": [{"family": "Abdulla", "given": "Maysaa", "initials": "M"}, {"family": "Hollander", "given": "Peter", "initials": "P", "orcid": "0000-0002-0226-5681", "researcher": {"href": "https://publications.scilifelab.se/researcher/b1c6693d3ede463eb78e6da010db601f.json"}}, {"family": "Pandzic", "given": "Tatjana", "initials": "T"}, {"family": "Mansouri", "given": "Larry", "initials": "L"}, {"family": "Ednersson", "given": "Susanne Bram", "initials": "SB"}, {"family": "Andersson", "given": "Per-Ola", "initials": "PO"}, {"family": "Hultdin", "given": "Magnus", "initials": "M"}, {"family": "Fors", "given": "Maja", "initials": "M"}, {"family": "Erlanson", "given": "Martin", "initials": "M"}, {"family": "Degerman", "given": "Sofie", "initials": "S", "orcid": "0000-0002-2783-0712", "researcher": {"href": "https://publications.scilifelab.se/researcher/8611162e883645f59195c4221199967f.json"}}, {"family": "Petersen", "given": "Helga Munch", "initials": "HM"}, {"family": "Asmar", "given": "Fazila", "initials": "F"}, {"family": "Gr\u00f8nbaek", "given": "Kirsten", "initials": "K"}, {"family": "Enblad", "given": "Gunilla", "initials": "G"}, {"family": "Cavelier", "given": "Lucia", "initials": "L", "orcid": "0009-0003-8195-370X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f01226edb140436da0c9d166c1f5fe51.json"}}, {"family": "Rosenquist", "given": "Richard", "initials": "R", "orcid": "0000-0002-0211-8788", "researcher": {"href": "https://publications.scilifelab.se/researcher/b570128e641140fb964ae3241414f510.json"}}, {"family": "Amini", "given": "Rose-Marie", "initials": "RM", "orcid": "0000-0003-0901-5252", "researcher": {"href": "https://publications.scilifelab.se/researcher/c157abcd61fa4900b5ad502b408d6d95.json"}}], "type": "journal article", "published": "2020-01-00", "journal": {"volume": "95", "issn": "1096-8652", "issue": "1", "pages": "57-67", "title": "Am. J. Hematol.", "issn-l": "0361-8609"}, "abstract": "The tumor cells in diffuse large B-cell lymphomas (DLBCL) are considered to originate from germinal center derived B-cells (GCB) or activated B-cells (ABC). Gene expression profiling (GEP) is preferably used to determine the cell of origin (COO). However, GEP is not widely applied in clinical practice and consequently, several algorithms based on immunohistochemistry (IHC) have been developed. Our aim was to evaluate the concordance of COO assignment between the Lymph2Cx GEP assay and the IHC-based Hans algorithm, to decide which model is the best survival predictor. Both GEP and IHC were performed in 359 homogenously treated Swedish and Danish DLBCL patients, in a retrospective multicenter cohort. The overall concordance between GEP and IHC algorithm was 72%; GEP classified 85% of cases assigned as GCB by IHC, as GCB, while 58% classified as non-GCB by IHC, were categorized as ABC by GEP. There were significant survival differences (overall survival and progression-free survival) if cases were classified by GEP, whereas if cases were categorized by IHC only progression-free survival differed significantly. Importantly, patients assigned as non-GCB/ABC both by IHC and GEP had the worst prognosis, which was also significant in multivariate analyses. Double expression of MYC and BCL2 was more common in ABC cases and was associated with a dismal outcome. In conclusion, to determine COO both by IHC and GEP is the strongest outcome predictor to identify DLBCL patients with the worst outcome.", "doi": "10.1002/ajh.25666", "pmid": "31659781", "labels": {"Clinical Genomics Uppsala": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC6916573"}], "notes": [], "created": "2019-11-29T13:25:33.461Z", "modified": "2024-01-16T13:48:43.178Z"}, {"entity": "publication", "iuid": "65e4b1d80b394c3cac3245642f6292c9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/65e4b1d80b394c3cac3245642f6292c9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/65e4b1d80b394c3cac3245642f6292c9"}}, "title": "Association of genetic variants related to plasma fatty acids with type 2 diabetes mellitus and glycaemic traits: a Mendelian randomisation study.", "authors": [{"family": "Yuan", "given": "Shuai", "initials": "S"}, {"family": "Larsson", "given": "Susanna C", "initials": "SC"}], "type": "journal article", "published": "2020-01-00", "journal": {"volume": "63", "issn": "1432-0428", "issue": "1", "pages": "116-123", "title": "Diabetologia", "issn-l": "0012-186X"}, "abstract": "Epidemiological data on the associations of circulating fatty acid levels with type 2 diabetes are inconsistent. We conducted a two-sample Mendelian randomisation study to explore the causal associations of plasma levels of ten fatty acids with type 2 diabetes and glycaemic traits.\n\nThirteen SNPs associated with circulating levels of ten individual fatty acids at the genome-wide significance level (p < 5 \u00d7 10-8) were selected as instrumental variables for the exposures. For the outcomes, summary-level data were obtained from the DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) consortium for type 2 diabetes (898,130 individuals) and from the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) for the glycaemic traits (up to 46,186 non-diabetic individuals). The inverse-variance weighted method was used for analyses.\n\nGenetic predisposition to higher plasma levels of eight of the ten fatty acids were statistically significantly associated with lower or higher odds of type 2 diabetes. The OR per one SD increment of each fatty acid was 0.93 (95% CI 0.90, 0.96; p = 2.21 \u00d7 10-5) for \u03b1-linolenic acid, 0.96 (95% CI 0.94, 0.98; p = 1.85 \u00d7 10-4) for linoleic acid, 0.86 (95% CI 0.81, 0.91; p = 6.68 \u00d7 10-7) for palmitoleic acid, 0.87 (95% CI 0.81, 0.93; p = 2.21 \u00d7 10-5) for oleic acid, 1.08 (95% CI 1.03, 1.12; p = 0.002) for eicosapentaenoic acid, 1.04 (95% CI 1.02, 1.07; p = 0.001) for docosapentaenoic acid, 1.03 (95% CI 1.02, 1.05; p = 2.51 \u00d7 10-5) for arachidonic acid and 1.09 (95% CI 1.03, 1.15; p = 0.003) for stearic acid. The same eight fatty acids were also associated with fasting glucose levels and HOMA-B. The associations, except that for palmitoleic acid, were driven by variants in FADS1/2.\n\nGenetic predisposition to higher circulating levels of eight out of ten fatty acids was associated with type 2 diabetes, fasting glucose and islet beta cell function. However, the associations, except that for palmitoleic acid, were driven by variants in FADS1/2, which encode enzymes with a key role in fatty acid metabolism.", "doi": "10.1007/s00125-019-05019-0", "pmid": "31690987", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "10.1007/s00125-019-05019-0"}, {"db": "pmc", "key": "PMC6890658"}], "notes": [], "created": "2020-01-14T10:04:58.804Z", "modified": "2024-01-16T13:48:43.229Z"}, {"entity": "publication", "iuid": "1054ba48e4d1461ab2bbd43b0fedfb1f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1054ba48e4d1461ab2bbd43b0fedfb1f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1054ba48e4d1461ab2bbd43b0fedfb1f"}}, "title": "Regeneration of water-deactivated Cu/SAPO-34(MO) with acids", "authors": [{"family": "Woo", "given": "Jungwon", "initials": "J"}, {"family": "Bernin", "given": "Diana", "initials": "D"}, {"family": "Ahari", "given": "Homayoun", "initials": "H"}, {"family": "Shost", "given": "Mark", "initials": "M"}, {"family": "Zammit", "given": "Michael", "initials": "M"}, {"family": "Olsson", "given": "Louise", "initials": "L", "orcid": "0000-0002-8308-0784", "researcher": {"href": "https://publications.scilifelab.se/researcher/0480749dd49d45919dae353a203fe6ef.json"}}], "type": "journal-article", "published": "2020-00-00", "journal": {"title": "Catal. Sci. Technol.", "issn": "2044-4753", "volume": "10", "issue": "5", "pages": "1539-1550", "issn-l": null}, "abstract": null, "doi": "10.1039/c9cy02031d", "pmid": null, "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [], "notes": [], "created": "2023-05-31T16:19:56.620Z", "modified": "2025-10-17T13:03:57.293Z"}, {"entity": "publication", "iuid": "2e9d703d4303487d9fd51f2e81e7f751", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2e9d703d4303487d9fd51f2e81e7f751.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2e9d703d4303487d9fd51f2e81e7f751"}}, "title": "In Situ Sequencing: A High-Throughput, Multi-Targeted Gene Expression Profiling Technique for Cell Typing in Tissue Sections", "authors": [{"family": "Hilscher", "given": "Markus M", "initials": "MM", "orcid": "0000-0001-7782-0830", "researcher": {"href": "https://publications.scilifelab.se/researcher/1de5317c53f34bc89dabfddb0be44983.json"}}, {"family": "Gyllborg", "given": "Daniel", "initials": "D"}, {"family": "Yokota", "given": "Chika", "initials": "C"}, {"family": "Nilsson", "given": "Mats", "initials": "M", "orcid": "0000-0001-9985-0387", "researcher": {"href": "https://publications.scilifelab.se/researcher/197cf8ba83ba430f9712b2f4d94dc3e5.json"}}], "type": "book-chapter", "published": "2020-00-00", "journal": {"title": "Methods Mol. Biol.", "issn": "1064-3745", "issn-l": null, "volume": "2148", "issue": null, "pages": "313-329"}, "abstract": "Recent advances of image-based in situ mRNA quantification methods allow to visualize where in a tissue section a set of genes is expressed. It enables to map large numbers of genes in parallel and by capturing cellular boundaries allows to assign genes to cells. Here, we present a high-throughput, multi-targeted gene expression profiling technique called in situ sequencing that is capable of localizing hundreds of genes simultaneously and supports cell type classifications that follow transcriptome-based taxonomy. In situ sequencing is a targeted, amplified, and barcoded approach using padlock probes (PLPs) and rolling circle amplification (RCA). The current protocol relies on mRNA fixation, mRNA reverse transcription, residual mRNA degradation, and PLP hybridization. PLPs are amplified by RCA and labeled with fluorophore-conjugated probes, allowing their detection under conventional fluorescence microscopes.", "doi": "10.1007/978-1-0716-0623-0_20", "pmid": "32394391", "labels": {"Bioinformatics Support for Computational Resources": "Service", "In Situ Sequencing": "Collaborative"}, "xrefs": [], "notes": [], "created": "2020-12-11T18:54:19.422Z", "modified": "2025-10-17T13:02:18.194Z"}, {"entity": "publication", "iuid": "1d79165edbf8478ca69c94264d108374", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1d79165edbf8478ca69c94264d108374.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1d79165edbf8478ca69c94264d108374"}}, "title": "An integrative toolbox to unlock the structure and dynamics of protein\u2013surfactant complexes", "authors": [{"family": "Sanchez-Fernandez", "given": "Adrian", "initials": "A", "orcid": "0000-0002-0241-1191", "researcher": {"href": "https://publications.scilifelab.se/researcher/a6d7f1d4ccd743e88aa10b4bae4c3b00.json"}}, {"family": "Diehl", "given": "Carl", "initials": "C"}, {"family": "Houston", "given": "Judith E", "initials": "JE", "orcid": "0000-0001-5205-3620", "researcher": {"href": "https://publications.scilifelab.se/researcher/f8ea55d08da74e2eabf3d0041bb5d728.json"}}, {"family": "Leung", "given": "Anna E", "initials": "AE"}, {"family": "Tellam", "given": "James P", "initials": "JP", "orcid": "0000-0001-9243-1323", "researcher": {"href": "https://publications.scilifelab.se/researcher/68f8568f66564cfaa2d8c6e070d67090.json"}}, {"family": "Rogers", "given": "Sarah E", "initials": "SE", "orcid": "0000-0003-2418-6965", "researcher": {"href": "https://publications.scilifelab.se/researcher/1bb1b0da7d334241824611b5d407a0a6.json"}}, {"family": "Prevost", "given": "Sylvain", "initials": "S", "orcid": "0000-0002-6008-1987", "researcher": {"href": "https://publications.scilifelab.se/researcher/3b2527a87de2432f86f7fab91c3ce41f.json"}}, {"family": "Ulvenlund", "given": "Stefan", "initials": "S", "orcid": "0000-0002-3686-6792", "researcher": {"href": "https://publications.scilifelab.se/researcher/4bcc9fd7086d4203b414ed02fb02d7c2.json"}}, {"family": "Sj\u00f6gren", "given": "Helen", "initials": "H", "orcid": "0000-0003-2592-1239", "researcher": {"href": "https://publications.scilifelab.se/researcher/3cb19c7d5b8c4611ae0ba909897603ca.json"}}, {"family": "Wahlgren", "given": "Marie", "initials": "M", "orcid": "0000-0002-1705-3964", "researcher": {"href": "https://publications.scilifelab.se/researcher/e2bb0f5208294feb8930acbe9cf7920b.json"}}], "type": "journal-article", "published": "2020-00-00", "journal": {"title": "Nanoscale Adv.", "issn": "2516-0230", "volume": "2", "issue": "9", "pages": "4011-4023", "issn-l": null}, "abstract": null, "doi": "10.1039/d0na00194e", "pmid": null, "labels": {"Swedish NMR Centre": "Service"}, "xrefs": [], "notes": [], "created": "2020-12-11T09:06:34.918Z", "modified": "2025-10-17T13:03:57.308Z"}, {"entity": "publication", "iuid": "32f0534e94db43eea801094c1f952714", "links": {"self": {"href": "https://publications.scilifelab.se/publication/32f0534e94db43eea801094c1f952714.json"}, "display": {"href": "https://publications.scilifelab.se/publication/32f0534e94db43eea801094c1f952714"}}, "title": "A Chemical Screen Identifies a Link between Lipid Metabolism and mRNA Translation", "authors": [{"family": "Corman", "given": "Alba", "initials": "A"}, {"family": "Kanellis", "given": "Dimitris C", "initials": "DC"}, {"family": "H\u00e4ggblad", "given": "Maria", "initials": "M"}, {"family": "Lafarga", "given": "Vanesa", "initials": "V"}, {"family": "Bartek", "given": "Jiri", "initials": "J"}, {"family": "Carreras-Puigvert", "given": "Jordi", "initials": "J"}, {"family": "Fernandez-Capetillo", "given": "Oscar", "initials": "O"}], "type": "journal-article", "published": "2020-00-00", "journal": {"title": "SSRN Journal", "issn": "1556-5068", "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": null, "doi": "10.2139/ssrn.3624440", "pmid": null, "labels": {"Chemical Biology Consortium Sweden": "Service"}, "xrefs": [], "notes": [], "created": "2020-09-25T11:21:09.506Z", "modified": "2025-10-17T13:04:28.417Z"}]}