{"entity": "label", "iuid": "87c265e8e290413785ad0575b18cf44a", "timestamp": "2026-08-10T16:56:34.524Z", "links": {"self": {"href": "https://publications.scilifelab.se/label/Clinical%20Genomics%20Link%C3%B6ping.json"}, "display": {"href": "https://publications.scilifelab.se/label/Clinical%20Genomics%20Link%C3%B6ping"}}, "value": "Clinical Genomics Link\u00f6ping", "started": "2019", "ended": "", "created": "2020-01-20T13:36:19.877Z", "modified": "2021-03-15T14:16:35.812Z", "accounts": [{"entity": "account", "iuid": "32a436398938412b93e7ddcef018c708", "timestamp": "2026-08-10T16:56:34.524Z", "links": {"self": {"href": "https://publications.scilifelab.se/account/christopher.erdmann%40scilifelab.uu.se.json"}, "display": {"href": "https://publications.scilifelab.se/account/christopher.erdmann%40scilifelab.uu.se"}}, "email": "christopher.erdmann@scilifelab.uu.se", "name": "Christopher Erdmann", "orcid": "", "role": "curator", "status": "enabled", "login": "2024-08-16T11:56:57.787Z", "created": "2024-08-16T10:01:32.844Z", "modified": "2025-10-17T13:05:06.782Z"}, {"entity": "account", "iuid": "5c73643633ed468288a652e84816df26", "timestamp": "2026-08-10T16:56:34.524Z", "links": {"self": {"href": "https://publications.scilifelab.se/account/malgorzata.lysiak%40liu.se.json"}, "display": {"href": "https://publications.scilifelab.se/account/malgorzata.lysiak%40liu.se"}}, "email": "malgorzata.lysiak@liu.se", "name": "Malgorzata Lysiak", "orcid": "", "role": "curator", "status": "enabled", "login": "2025-11-28T11:32:05.684Z", "created": "2023-12-01T15:41:35.636Z", "modified": "2025-11-28T11:32:05.684Z"}, {"entity": "account", "iuid": "6a38350bd21f4fb6aeeb1530037a99ae", "timestamp": "2026-08-10T16:56:34.524Z", "links": {"self": {"href": "https://publications.scilifelab.se/account/sune.joubert%40scilifelab.uu.se.json"}, "display": {"href": "https://publications.scilifelab.se/account/sune.joubert%40scilifelab.uu.se"}}, "email": "sune.joubert@scilifelab.uu.se", "name": "Sun\u00e9 Joubert", "orcid": "", "role": "curator", "status": "enabled", "login": "2025-10-31T11:15:37.113Z", "created": "2024-08-16T10:01:02.800Z", "modified": "2025-10-31T11:15:37.113Z"}, {"entity": "account", "iuid": "6bbcd0b326144a56a03bafed3c192c6b", "timestamp": "2026-08-10T16:56:34.524Z", "links": {"self": {"href": "https://publications.scilifelab.se/account/tobias.strid%40liu.se.json"}, "display": {"href": "https://publications.scilifelab.se/account/tobias.strid%40liu.se"}}, "email": "tobias.strid@liu.se", "name": "Tobias Strid", "orcid": "", "role": "curator", "status": "enabled", "login": "2022-12-01T14:01:27.163Z", "created": "2020-11-05T12:18:47.690Z", "modified": "2025-03-07T13:49:04.932Z"}, {"entity": "account", "iuid": "bc7b23448fec49d6a7f913b7ad0e82b6", "timestamp": "2026-08-10T16:56:34.524Z", "links": {"self": {"href": "https://publications.scilifelab.se/account/colum.walsh%40liu.se.json"}, "display": {"href": 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"https://publications.scilifelab.se/publication/7f1ea59b281c4f869a2b8e7a6dc5d6dd.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7f1ea59b281c4f869a2b8e7a6dc5d6dd"}}, "title": "Decoding murine corneal epithelial specification and homeostasis by single-cell spatial transcriptomics with scRNA-seq enrichment", "authors": [{"family": "Javidjam", "given": "Dina", "initials": "D", "orcid": "0000-0003-4436-5928", "researcher": {"href": "https://publications.scilifelab.se/researcher/69cc19a0f07b4e16a33bb9ff5114eced.json"}}, {"family": "Vattulainen", "given": "Meri", "initials": "M", "orcid": "0000-0003-1343-1232", "researcher": {"href": "https://publications.scilifelab.se/researcher/5c70e5d8ac9b418bbfd25c851492716e.json"}}, {"family": "Lagali", "given": "Neil", "initials": "N", "orcid": "0000-0003-1079-4361", "researcher": {"href": "https://publications.scilifelab.se/researcher/a6d3fe5278714b4784551cdcc8166aa1.json"}}, {"family": "Moustardas", "given": "Petros", "initials": "P", "orcid": "0000-0003-3192-3708", "researcher": {"href": "https://publications.scilifelab.se/researcher/eddb470abb044abebf415daa656c77df.json"}}], "type": "posted-content", "published": "2026-05-12", "journal": {"issn-l": null}, "abstract": null, "doi": "10.64898/2026.05.08.723186", "pmid": null, "labels": {"Clinical Genomics": "Service", "Clinical Genomics Link\u00f6ping": "Service"}, "xrefs": [], "notes": [], "created": "2026-05-19T07:32:34.862Z", "modified": "2026-07-10T08:26:49.186Z"}, {"entity": "publication", "iuid": "67eb0d7fc75a45f8a47f45fc5243daa7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/67eb0d7fc75a45f8a47f45fc5243daa7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/67eb0d7fc75a45f8a47f45fc5243daa7"}}, "title": "Differential negative dominance by KCNA2 variants associated with global developmental delay suggests KCNA2 haploinsufficiency in humans.", "authors": [{"family": "Boon", "given": "Pei Xin", "initials": "PX", "orcid": "0009-0001-4366-4507", "researcher": {"href": "https://publications.scilifelab.se/researcher/d037eb59a4144be1a05c7b830a8c0929.json"}}, {"family": "Jauregi-Miguel", "given": "Amaia", "initials": "A", "orcid": "0000-0003-0938-7734", "researcher": {"href": "https://publications.scilifelab.se/researcher/bd678c2b74f74975a83ca102fa473752.json"}}, {"family": "Yasarbas", "given": "S Suheda", "initials": "SS", "orcid": "0009-0002-8528-2539", "researcher": {"href": "https://publications.scilifelab.se/researcher/2b15e89897e04bedaf5b070a03959a9f.json"}}, {"family": "Pozzi", "given": "Serena", "initials": "S", "orcid": "0009-0009-2688-1575", "researcher": {"href": "https://publications.scilifelab.se/researcher/ab10411118ea486d9fa1fc348cb306cd.json"}}, {"family": "Karlsson", "given": "Urban", "initials": "U", "orcid": "0000-0002-9228-1625", "researcher": {"href": "https://publications.scilifelab.se/researcher/eb7fa0354374416ca2f928c56f4ffe81.json"}}, {"family": "Husami", "given": "Ammar", "initials": "A", "orcid": "0000-0002-4287-2857", "researcher": {"href": "https://publications.scilifelab.se/researcher/6ec9d6ec3af24a5bb2a163b323835d74.json"}}, {"family": "Ko", "given": "Charmaine", "initials": "C", "orcid": "0009-0003-1026-8836", "researcher": {"href": "https://publications.scilifelab.se/researcher/002ecdac5e4a4ca59b39b21ed2d10d54.json"}}, {"family": "Shillington", "given": "Amelle", "initials": "A", "orcid": "0000-0002-7447-8117", "researcher": {"href": "https://publications.scilifelab.se/researcher/bd9ab021d089429baf50a212a59ca1a8.json"}}, {"family": "Pantazis", "given": "Antonios", "initials": "A", "orcid": "0000-0002-6467-1327", "researcher": {"href": "https://publications.scilifelab.se/researcher/810aaa85bf734f03a9e25e0651b45c19.json"}}], "type": "journal article", "published": "2026-04-00", "journal": {"title": "J Physiol", "issn": "1469-7793", "volume": "604", "issue": "8", "pages": "3413-3430", "issn-l": null}, "abstract": "KCNA2 encodes the pore-forming subunits of the voltage-gated, potassium-selective channel KV1.2, which controls the excitability of both central and peripheral neurons. Either gain- or loss-of-function KCNA2 variants can cause severe neurological disease, assigned developmental epileptic encephalopathy (DEE) type 32. Here, we report and characterize two apparently similar variants, p.H310D and p.G318D, both discovered in patients with global developmental delay and involving aspartate substitutions at positions highly conserved in the KV-channel superfamily. We found that both are loss-of-function variants, completely abolishing channel current and subunit trafficking. Channel constructs of KV1.2-variant subunits in tandem with KV1.4 had a conductance with inhibited voltage-dependence, with shifted half-activation potentials by 27 and 19 mV for p.H310D and p.G318D, respectively. p.H310D was strongly negative-dominant: heterozygous cells exhibited only 7% conductance relative to homozygous wild-type, while only half of wild-type subunits could traffic to the surface. In contrast, p.G318D exhibited weaker negative dominance, with 32% conductance in heterozygous cells and 86% wild-type-subunit trafficking. Taken together with the p.G318D-patient's neurological symptoms, the latter suggests that KCNA2 is a haploinsufficient gene in humans. KEY POINTS: KCNA2 encodes the pore-forming subunits of the KV1.2 voltage-activated, K+-selective ion channel, which regulates electrical signalling in neurons. We characterized two KCNA2 variants from patients with global developmental delay. Both variants are aspartate substitutions of proximal, highly conserved positions in KV-channels: p.H310D and p.G318D. In frog oocytes and in primate cells, both variants cause loss of KCNA2 function, abolishing currents and surface trafficking, and inhibiting channel voltage-dependent opening. p.H310D is strongly negative-dominant, potently suppressing wild-type subunit functional expression. In contrast, p.G318D is weakly negative-dominant, leaving wild-type subunits largely unaffected. This suggests that KCNA2 is a haploinsufficient gene in humans.", "doi": "10.1113/JP290728", "pmid": "41914769", "labels": {"Clinical Genomics": "Service", "Clinical Genomics Link\u00f6ping": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC13082188"}], "notes": [], "created": "2026-05-19T07:50:00.374Z", "modified": "2026-05-19T07:50:43.828Z"}, {"entity": "publication", "iuid": "7113a2d0392946c48648bba31fb03588", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7113a2d0392946c48648bba31fb03588.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7113a2d0392946c48648bba31fb03588"}}, "title": "Integrative Epigenomic and Transcriptomic Profiling Define Malignancy- and Cluster-Specific Signatures in Pheochromocytomas and Paragangliomas", "authors": [{"family": "Tabebi", "given": "Mouna", "initials": "M", "orcid": "0000-0002-2873-161X", "researcher": {"href": "https://publications.scilifelab.se/researcher/285705c043f34b55826e7f33ab36a875.json"}}, {"family": "\u0141ysiak", "given": "Ma\u0142gorzata", "initials": "M", "orcid": "0000-0002-0244-759X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a7f5d37e79764c31a5a0a421c34ed1a8.json"}}, {"family": "Gimm", "given": "Oliver", "initials": "O", "orcid": "0000-0002-0054-664X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9879641fb40042ae90ff034f4912a16d.json"}}, {"family": "S\u00f6derkvist", "given": "Peter", "initials": "P"}], "type": "journal-article", "published": "2026-01-20", "journal": {"title": "Cells", "issn": "2073-4409", "volume": "15", "issue": "2", "pages": "198", "issn-l": "2073-4409"}, "abstract": null, "doi": "10.3390/cells15020198", "pmid": null, "labels": {"Clinical Genomics": "Service", "Clinical Genomics Link\u00f6ping": "Collaborative"}, "xrefs": [], "notes": [], "created": "2026-01-26T09:31:12.459Z", "modified": "2026-01-26T09:32:30.489Z"}, {"entity": "publication", "iuid": "996018f364704a1abe996db7068a45d8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/996018f364704a1abe996db7068a45d8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/996018f364704a1abe996db7068a45d8"}}, "title": "Phylum-wide propionate degradation and its potential connection to poly-gamma-glutamate biosynthesis in Candidatus Cloacimonadota phylum.", "authors": [{"family": "Calusinska", "given": "Magdalena", "initials": "M", "orcid": "0000-0003-2270-2217", "researcher": {"href": "https://publications.scilifelab.se/researcher/f184fc41010f4815b8ba4a2203bdab1b.json"}}, {"family": "Herold", "given": "Malte", "initials": "M", "orcid": "0000-0003-2627-0159", "researcher": {"href": "https://publications.scilifelab.se/researcher/70759c28794141fbb123901947534ec4.json"}}, {"family": "Klimek", "given": "Dominika", "initials": "D", "orcid": "0000-0002-6713-8333", "researcher": {"href": "https://publications.scilifelab.se/researcher/39f020f1807c426c988f2ba6a8d6ac2e.json"}}, {"family": "Bertucci", "given": "Marie", "initials": "M", "orcid": "0009-0003-5131-0746", "researcher": {"href": "https://publications.scilifelab.se/researcher/139ca2da31b34ebe9104aa4f370a937b.json"}}, {"family": "Lemaigre", "given": "S\u00e9bastien", "initials": "S", "orcid": "0000-0002-3204-293X", "researcher": {"href": "https://publications.scilifelab.se/researcher/dfe56744791c4ef1a59a7eb187ded69f.json"}}, {"family": "Cambier", "given": "S\u00e9bastien", "initials": "S"}, {"family": "Zorzan", "given": "Simone", "initials": "S"}, {"family": "Leclercq", "given": "C\u00e9line", "initials": "C", "orcid": "0000-0003-0565-4591", "researcher": {"href": "https://publications.scilifelab.se/researcher/13f9babdf8e24b7098ab25c45af2c06a.json"}}, {"family": "Dolfing", "given": "Jan", "initials": "J", "orcid": "0000-0002-7220-530X", "researcher": {"href": "https://publications.scilifelab.se/researcher/13c979337df149d78d462df170b54296.json"}}, {"family": "Westerholm", "given": "Maria", "initials": "M", "orcid": "0000-0003-2150-8762", "researcher": {"href": "https://publications.scilifelab.se/researcher/773b448833474db9aef273531d590892.json"}}, {"family": "M\u00fcller", "given": "Bettina", "initials": "B", "orcid": "0000-0002-0030-7710", "researcher": {"href": "https://publications.scilifelab.se/researcher/4c1cb5bfdb1a4ceaa551d5908b54e062.json"}}, {"family": "Nasirzadeh", "given": "Leila", "initials": "L", "orcid": "0000-0003-0282-1227", "researcher": {"href": "https://publications.scilifelab.se/researcher/d9465e8d872740a083579657d96bb431.json"}}, {"family": "Schn\u00fcrer", "given": "Anna", "initials": "A", "orcid": "0000-0003-0038-553X", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f81992bc8ed48318f8197fc8caabb4f.json"}}, {"family": "Wilmes", "given": "Paul", "initials": "P", "orcid": "0000-0002-6478-2924", "researcher": {"href": "https://publications.scilifelab.se/researcher/a0fa4b91d7384fda991fcda7c3df41be.json"}}, {"family": "Delfosse", "given": "Philippe", "initials": "P", "orcid": "0009-0003-9371-209X", "researcher": {"href": "https://publications.scilifelab.se/researcher/85d6d628631f4012941393e3b7f03a64.json"}}, {"family": "Goux", "given": "Xavier", "initials": "X", "orcid": "0000-0002-0815-2194", "researcher": {"href": "https://publications.scilifelab.se/researcher/2ee58ca55da3480b864a0a26f15649ae.json"}}], "type": "journal article", "published": "2026-01-14", "journal": {"title": "ISME J", "issn": "1751-7370", "volume": "20", "issue": "1", "issn-l": "1751-7362"}, "abstract": "The candidate phylum Cloacimonadota is frequently detected in anoxic environments such as anaerobic digestion (AD) reactors, hydrothermal vents, and deep-sea sediments, yet its metabolism remains poorly understood. Metagenomic evidence suggests capacities for amino acid fermentation, carbohydrate degradation, as well as a potential role in syntrophic propionate oxidation (SPO), a key bottleneck in AD. However, a complete methylmalonyl-CoA (mmc) pathway, central to SPO, has not been previously identified in Cloacimonadota genomes. Here, we report results from an acidified lab-scale anaerobic baffled reactor fed with sugar beet pulp, where an increase in the relative abundance of Cloacimonadota correlated with recovery of methanogenesis, resulting in increased methane content in the produced biogas. Metagenomic and metatranscriptomic analyses enabled metabolic reconstruction of the dominant Cloacimonadota operational taxonomic unit (OTU). Furthermore, using a curated database of 204 genome-resolved Cloacimonadota species, we characterized the phylum-level metabolic potential. Comparative genomics revealed alternative proteins, including 2-oxoglutarate:ferredoxin oxidoreductase and aspartate aminotransferase, likely to substitute for missing enzymes in the classical mmc pathway. These proteins were widely distributed and highly conserved across the analyzed Cloacimonadota genomes, suggesting that this variant of the SPO pathway could represent a phylum-specific trait. Moreover, we hypothesize that these alternative pathway steps may link propionate metabolism to protein degradation and poly-\u03b3-glutamate biosynthesis. Network analysis identified the methanogenic archaeon Methanothrix as a potential syntrophic partner, an interaction further supported by propionate-fed enrichment cultures showing co-occurrence of Cloacimonadota and Methanothrix species. Our study sheds light on the Cloacimonadota metabolism, advancing our understanding of their ecological roles and potential for biotechnological applications.", "doi": "10.1093/ismejo/wrag055", "pmid": "41848058", "labels": {"Clinical Genomics": "Collaborative", "Clinical Genomics Link\u00f6ping": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC13082233"}, {"db": "pii", "key": "8527530"}], "notes": [], "created": "2026-06-09T06:06:08.699Z", "modified": "2026-06-09T06:06:09.571Z"}, {"entity": "publication", "iuid": "83a77d8160924330b81be0f9c36ddd00", "links": {"self": {"href": "https://publications.scilifelab.se/publication/83a77d8160924330b81be0f9c36ddd00.json"}, "display": {"href": "https://publications.scilifelab.se/publication/83a77d8160924330b81be0f9c36ddd00"}}, "title": "Altered DNA Methylation Pattern Contributes to Differential Epigenetic Immune Signaling in the Upper Respiratory Airway of Unvaccinated COVID-19 Patients", "authors": [{"family": "Govender", "given": "Melissa", "initials": "M", "orcid": "0000-0001-8327-5517", "researcher": {"href": "https://publications.scilifelab.se/researcher/0283324530c24dc59a856cc26f202884.json"}}, {"family": "Das", "given": "Jyotirmoy", "initials": "J", "orcid": "0000-0002-5649-4658", "researcher": {"href": "https://publications.scilifelab.se/researcher/ebcbc4237c1c48aeb6bdd446fd8d2c8a.json"}}, {"family": "Hopkins", "given": "Francis R", "initials": "FR"}, {"family": "Svanberg", "given": "Cecilia", "initials": "C"}, {"family": "Nordgren", "given": "Johan", "initials": "J", "orcid": "0000-0002-5349-2569", "researcher": {"href": "https://publications.scilifelab.se/researcher/81437aaae3b44d148e838a184c455f2b.json"}}, {"family": "Hagbom", "given": "Marie", "initials": "M", "orcid": "0000-0002-9770-4623", "researcher": {"href": "https://publications.scilifelab.se/researcher/0555f8ab1b2d42fc9bead5f4c0240ec9.json"}}, {"family": "Klingstr\u00f6m", "given": "Jonas", "initials": "J"}, {"family": "Nilsdotter-Augustinsson", "given": "\u00c5sa", "initials": "\u00c5", "orcid": "0000-0001-5719-5601", "researcher": {"href": "https://publications.scilifelab.se/researcher/129ff8d1d877437fbf37f4180ea19fb4.json"}}, {"family": "Yong", "given": "Yean K", "initials": "YK"}, {"family": "Velu", "given": "Vijayakumar", "initials": "V", "orcid": "0000-0003-4238-1924", "researcher": {"href": "https://publications.scilifelab.se/researcher/61fbbd07ba5341f087bfcc958246792a.json"}}, {"family": "Raju", "given": "Sivadoss", "initials": "S"}, {"family": "Sj\u00f6wall", "given": "Johanna", "initials": "J", "orcid": "0000-0001-5622-866X", "researcher": {"href": "https://publications.scilifelab.se/researcher/6442643a54484b3e9a6bfd586f2c27dc.json"}}, {"family": "Shankar", "given": "Esaki M", "initials": "EM", "orcid": "0000-0002-7866-9818", "researcher": {"href": "https://publications.scilifelab.se/researcher/1edec2d2bca84f3499109c5135436309.json"}}, {"family": "Nystr\u00f6m", "given": "Sofia", "initials": "S", "orcid": "0000-0002-0145-4966", "researcher": {"href": "https://publications.scilifelab.se/researcher/93a23955db724558abca4e7ed1265067.json"}}, {"family": "Larsson", "given": "Marie", "initials": "M", "orcid": "0000-0002-4524-0177", "researcher": {"href": "https://publications.scilifelab.se/researcher/46874786a8de48668401faba73165750.json"}}], "type": "journal-article", "published": "2025-10-27", "journal": {"title": "Cells", "issn": "2073-4409", "issn-l": "2073-4409", "volume": "14", "issue": "21", "pages": "1673"}, "abstract": null, "doi": "10.3390/cells14211673", "pmid": null, "labels": {"Clinical Genomics": "Service", "Clinical Genomics Link\u00f6ping": "Collaborative"}, "xrefs": [], "notes": [], "created": "2025-10-30T12:39:09.525Z", "modified": "2025-10-30T12:40:16.743Z"}, {"entity": "publication", "iuid": "cd69deb28cb34a7ba0f06bcbdcde1b23", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cd69deb28cb34a7ba0f06bcbdcde1b23.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cd69deb28cb34a7ba0f06bcbdcde1b23"}}, "title": "Role of GDH and PARP inhibitors as novel treatments for SDHB-deficient PPGLs.", "authors": [{"family": "Tabebi", "given": "Mouna", "initials": "M", "orcid": "0000-0002-2873-161X", "researcher": {"href": "https://publications.scilifelab.se/researcher/285705c043f34b55826e7f33ab36a875.json"}}, {"family": "Abdallah", "given": "Sallam", "initials": "S"}, {"family": "El-Serafi", "given": "Ahmed", "initials": "A"}, {"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": "2025-10-01", "journal": {"title": "Endocr. Relat. Cancer", "issn": "1479-6821", "issn-l": "1351-0088", "volume": "32", "issue": "10", "pages": null}, "abstract": "SDHB, one of the four genes encoding the subunits of the Krebs cycle enzyme succinate dehydrogenase (SDH), acts as a tumor suppressor in several human cancers, including pheochromocytomas/paragangliomas. Mutations in SDHB lead to a reduction or complete loss of enzymatic activity, linking SDHB to paraganglioma malignancy. Given the difficulty in curing metastatic paragangliomas and the limited value of surgery, new treatments are needed. Glutamine dehydrogenase 1 (GDH1), a key regulator of glutathione metabolism, and poly (ADP-ribose) polymerase (PARP), essential for repairing single- or double-stranded DNA breaks, are crucial in cancer initiation and progression. We treated the human pheochromocytoma cell line (hPheo1) with knocked-down SDHB using radiation, the GDH inhibitor 'R162', and the PARP inhibitor 'olaparib'. Combining R162 with radiation enhances anticancer effectiveness, reduces cell proliferation, and causes G2/M phase arrest in the wild-type and KD-SDHB hPheo1 cell line. KD-SDHB hPheo1 cells treated with olaparib alone were more resistant than wild-type cells but were more sensitive in combination with radiation, activated repair mechanisms, and halted cell cycle progression at the G2/M phase. These results suggest that enhancing radiation-induced DNA damage could be a potential treatment strategy for metastatic pheochromocytomas/paragangliomas. Inhibiting GDH1 and PARP activities, with radiation, may represent promising strategies for the treatment of SDHB-deficient pheochromocytoma/paraganglioma; however, their effects do not appear to be specific to SDHB-deficient cells and require further validation.", "doi": "10.1530/ERC-25-0173", "pmid": "40990469", "labels": {"Clinical Genomics": "Collaborative", "Clinical Genomics Link\u00f6ping": "Collaborative"}, "xrefs": [{"db": "pii", "key": "ERC-25-0173"}], "notes": [], "created": "2025-10-09T06:57:26.582Z", "modified": "2025-11-04T09:44:51.833Z"}, {"entity": "publication", "iuid": "90b8a5b9723c42228207d46e91919ff8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/90b8a5b9723c42228207d46e91919ff8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/90b8a5b9723c42228207d46e91919ff8"}}, "title": "Topical MTH1 Inhibition Suppresses SKP2-WNT5a-Driven Psoriatic Hyperproliferation", "authors": [{"family": "Bivik Eding", "given": "Cecilia", "initials": "C", "orcid": "0000-0003-2769-0016", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe41fe488cc34311a78037b2c7cee09b.json"}}, {"family": "K\u00f6hler", "given": "Ines", "initials": "I", "orcid": "0000-0002-9260-8528", "researcher": {"href": "https://publications.scilifelab.se/researcher/38cf202fae2a4a9fb1a892023899a497.json"}}, {"family": "Moparthi", "given": "Lavanya", "initials": "L", "orcid": "0000-0002-6030-3084", "researcher": {"href": "https://publications.scilifelab.se/researcher/c2207da5d7d34dd2a8def5239eaf351d.json"}}, {"family": "Sj\u00f6gren", "given": "Florence", "initials": "F"}, {"family": "Andersson", "given": "Blanka", "initials": "B", "orcid": "0000-0002-9562-0872", "researcher": {"href": "https://publications.scilifelab.se/researcher/df74d95228ec4e4583fd0a7f9dfd0317.json"}}, {"family": "Das", "given": "Debojyoti", "initials": "D", "orcid": "0000-0001-6811-3333", "researcher": {"href": "https://publications.scilifelab.se/researcher/4c763bab024a492d8e534a1e541c21dc.json"}}, {"family": "Verma", "given": "Deepti", "initials": "D"}, {"family": "Scobie", "given": "Martin", "initials": "M"}, {"family": "Warpman Berglund", "given": "Ulrika", "initials": "U"}, {"family": "Enerb\u00e4ck", "given": "Charlotta", "initials": "C", "orcid": "0000-0003-1769-3790", "researcher": {"href": "https://publications.scilifelab.se/researcher/492c35e3b7b44e23933cb0f91c721af3.json"}}], "type": "journal-article", "published": "2025-07-25", "journal": {"title": "Int J Mol Sci", "issn": "1422-0067", "volume": "26", "issue": "15", "pages": "7174", "issn-l": null}, "abstract": null, "doi": "10.3390/ijms26157174", "pmid": null, "labels": {"Clinical Genomics Link\u00f6ping": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [], "notes": [], "created": "2025-08-06T13:43:31.717Z", "modified": "2025-08-06T13:44:10.161Z"}, {"entity": "publication", "iuid": "ea0141d3c2e3447facf702d344e4d0f3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ea0141d3c2e3447facf702d344e4d0f3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ea0141d3c2e3447facf702d344e4d0f3"}}, "title": "Small RNA in sperm-Paternal contributions to human embryo development.", "authors": [{"family": "Isacson", "given": "Signe", "initials": "S", "orcid": "0000-0002-7590-8326", "researcher": {"href": "https://publications.scilifelab.se/researcher/c0cb5b0f3f694a10abf049f9e9c298e3.json"}}, {"family": "Karlsson", "given": "Kajsa", "initials": "K", "orcid": "0009-0002-7481-6291", "researcher": {"href": "https://publications.scilifelab.se/researcher/5f9727c26319451fab05d0646447c9c3.json"}}, {"family": "Zalavary", "given": "Stefan", "initials": "S", "orcid": "0000-0001-5209-6655", "researcher": {"href": "https://publications.scilifelab.se/researcher/5ccbf5fd93a3471d828865b7da39571e.json"}}, {"family": "Asratian", "given": "Anna", "initials": "A", "orcid": "0000-0001-7696-0508", "researcher": {"href": "https://publications.scilifelab.se/researcher/420e14758e1f45e9bf5f8a37f0115eae.json"}}, {"family": "Kugelberg", "given": "Unn", "initials": "U"}, {"family": "Liffner", "given": "Susanne", "initials": "S"}, {"family": "\u00d6st", "given": "Anita", "initials": "A", "orcid": "0000-0003-0547-1904", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7a222183b264e4b828a38c322a4090f.json"}}], "type": "journal article", "published": "2025-07-17", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "16", "issue": "1", "pages": "6571", "issn-l": "2041-1723"}, "abstract": "Sperm not only delivers the paternal genome to the oocyte but also regulatory small RNA (sRNA). However, the role of sRNA in fertilisation and human embryo development remains poorly understood. Here, couples undergoing IVF are recruited, and sperm sRNA analysed to investigate their role in IVF treatment. Differential expression of mitochondrial sRNA and Y-RNA are observed in relation to sperm concentration. For fertilisation rate, sRNA from a single locus are significantly changed. Expression of microRNA (miRNA) and ribosomal sRNA correlates positively and negatively, respectively, to high-quality embryos. Notably, the top miRNA have an area under ROC of >0.8. Predicted targets of these miRNA are relevant for development, suggesting a role for sperm-borne miRNA in embryo development. In conclusion, sperm-borne sRNA are biomarkers for sperm concentration and embryo quality in IVF. These findings may contribute to clinical strategies improving embryo quality, lowering costs and reducing the need for additional treatment cycles.", "doi": "10.1038/s41467-025-62015-2", "pmid": "40670377", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12267487"}, {"db": "pii", "key": "10.1038/s41467-025-62015-2"}], "notes": [], "created": "2025-08-11T10:09:40.254Z", "modified": "2025-08-11T10:09:40.970Z"}, {"entity": "publication", "iuid": "b5b7416273ac451f87d00bf6e94d1d70", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b5b7416273ac451f87d00bf6e94d1d70.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b5b7416273ac451f87d00bf6e94d1d70"}}, "title": "Rescue of loss-of-function long QT syndrome-associated mutations in KV7.1/KCNE1 by the endocannabinoid N-arachidonoyl-L-serine (ARA-S).", "authors": [{"family": "Hiniesto-I\u00f1igo", "given": "Irene", "initials": "I"}, {"family": "Sridhar", "given": "Akshay", "initials": "A"}, {"family": "Louradour", "given": "Julien", "initials": "J", "orcid": "0000-0002-0649-4975", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f26502cc6a74826b18e6b0b44ce711b.json"}}, {"family": "De la Cruz", "given": "Alicia", "initials": "A"}, {"family": "Lundholm", "given": "Siri", "initials": "S"}, {"family": "Jauregi-Miguel", "given": "Amaia", "initials": "A"}, {"family": "Giannetti", "given": "Federica", "initials": "F", "orcid": "0000-0002-1785-5529", "researcher": {"href": "https://publications.scilifelab.se/researcher/090b646375e94881b957c9ded9320cb2.json"}}, {"family": "Sala", "given": "Luca", "initials": "L", "orcid": "0000-0002-4129-6632", "researcher": {"href": "https://publications.scilifelab.se/researcher/6bdf4fd6470c46f1be65535eae085f44.json"}}, {"family": "Odening", "given": "Katja E", "initials": "KE", "orcid": "0000-0001-6999-841X", "researcher": {"href": "https://publications.scilifelab.se/researcher/5aa57ed2bc334eebada9236568f3ce81.json"}}, {"family": "Larsson", "given": "H Peter", "initials": "HP", "orcid": "0000-0002-1688-2525", "researcher": {"href": "https://publications.scilifelab.se/researcher/56340cab3dcd434ab18c86a949206e16.json"}}, {"family": "Ottosson", "given": "Nina E", "initials": "NE", "orcid": "0000-0003-2159-6731", "researcher": {"href": "https://publications.scilifelab.se/researcher/5e54acedff4e45bbaa661096b33f8f7c.json"}}, {"family": "Liin", "given": "Sara I", "initials": "SI", "orcid": "0000-0001-8493-0114", "researcher": {"href": "https://publications.scilifelab.se/researcher/e82a591108f24dcabf50779d88fc8844.json"}}], "type": "journal article", "published": "2025-07-00", "journal": {"title": "British Journal of Pharmacology", "issn": "1476-5381", "issn-l": "0007-1188", "volume": "182", "issue": "13", "pages": "2861-2877"}, "abstract": "Congenital long QT syndrome (LQTS) involves genetic mutations affecting ion channels, leading to a prolonged QT interval and increased risk of potentially lethal ventricular arrhythmias. Mutations in the genes encoding KV7.1/KCNE1 are the most frequent, with channel loss-of-function contributing to LQTS. The endocannabinoid N-arachidonoyl-L-serine (ARA-S) has been shown to facilitate activation of wild type KV7.1/KCNE1 channels and to counteract a prolonged QT interval in isolated guinea pig hearts. In this study, we examine the ability of ARA-S to facilitate activation of LQTS-associated mutations, in various regions of the channel, and hence to counteract loss-of-function.\n\nThe two-electrode voltage clamp technique on Xenopus oocytes expressing human KV7.1/KCNE1 channels was used to investigate the effects of ARA-S in 20 LQTS type 1-associated mutations distributed across the channel. Thereafter, different electrophysiology was used to assess ARA-S effects in mammalian cells.\n\nARA-S enhanced the function of all mutated channels by shifting V50 and increasing current amplitude. However, the magnitude of effect varied, related to whether mutations were in one of the two putative ARA-S binding sites on the channel as suggested by molecular dynamics simulations. ARA-S displayed translational potential by facilitating channel opening in mammalian cells and shortening the action potential duration in cardiomyocytes.\n\nThis study demonstrates the rescuing capability of ARA-S on a diverse set of LQTS mutants. These insights may aid in developing drug compounds using ARA-S sites and mechanisms and guide interpretation of which LQTS mutants respond well to such compounds.", "doi": "10.1111/bph.70008", "pmid": "40083204", "labels": {"Chemical Biology Consortium Sweden": "Collaborative", "Clinical Genomics": "Service", "Clinical Genomics Link\u00f6ping": "Service"}, "xrefs": [], "notes": [], "created": "2025-11-18T09:19:04.181Z", "modified": "2025-11-28T11:33:53.532Z"}, {"entity": "publication", "iuid": "aeb9fc21fabb4b8f8b5a91ef25b0c7a8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/aeb9fc21fabb4b8f8b5a91ef25b0c7a8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/aeb9fc21fabb4b8f8b5a91ef25b0c7a8"}}, "title": "Antimicrobial resistance and serotype distribution of Salmonella spp. isolated from fresh foods in Cambodia.", "authors": [{"family": "Huoy", "given": "Laingshun", "initials": "L", "orcid": "0000-0002-0194-4754", "researcher": {"href": "https://publications.scilifelab.se/researcher/6683581dbb2448008f33711ca1ada131.json"}}, {"family": "Nasirzadeh", "given": "Leila", "initials": "L", "orcid": "0000-0003-0282-1227", "researcher": {"href": "https://publications.scilifelab.se/researcher/d9465e8d872740a083579657d96bb431.json"}}, {"family": "Phan", "given": "Kongkea", "initials": "K", "orcid": "0000-0003-2965-8415", "researcher": {"href": "https://publications.scilifelab.se/researcher/0826a7f731ac490b84b1e6823b9cedb5.json"}}, {"family": "Tieng", "given": "Siteng", "initials": "S", "orcid": "0000-0002-9037-6671", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd94295461f642cca1a44b46e4b923a2.json"}}, {"family": "Sternberg-Lewerin", "given": "Susanna", "initials": "S", "orcid": "0000-0001-7907-8377", "researcher": {"href": "https://publications.scilifelab.se/researcher/41bff7b199434422b316875f399f5ebe.json"}}, {"family": "Bongcam-Rudloff", "given": "Erik", "initials": "E", "orcid": "0000-0002-1947-8288", "researcher": {"href": "https://publications.scilifelab.se/researcher/6970ca57259d498588ecf9e1ad28a9b0.json"}}, {"family": "Boqvist", "given": "Sofia", "initials": "S", "orcid": "0000-0002-8072-7132", "researcher": {"href": "https://publications.scilifelab.se/researcher/04e91c7a79164ce88c1a2aeaed836ca7.json"}}], "type": "journal article", "published": "2025-06-02", "journal": {"title": "J Appl Microbiol", "issn": "1365-2672", "volume": "136", "issue": "6", "issn-l": "1364-5072"}, "abstract": "To determine the Salmonella serotype distribution, antimicrobial resistance profiles, and antimicrobial resistance genes (ARGs) in food samples obtained from local markets in a low-income urban setting and nearby farms in Cambodia.\n\nOne hundred and thirty-nine Salmonella isolates from various food sources were tested for antibiotic susceptibility using a panel of 12 antibiotics, and 81 selected Salmonella isolates were further sequenced for serotype distribution and ARG identification. The results showed that 71% (99/139) of the isolates exhibited resistance to at least one antibiotic, with 39% (39/99) classified as multidrug-resistant (MDR). The highest resistance was observed against azithromycin (37%), followed by oxytetracycline (35%). A total of 32 serotypes were identified, with the six most common being S. Corvallis (7%), S. Haifa (6%), S. Weltevreden (6%), S. Agona (5%), S. Kentucky (5%), and S. Livingstone (5%). A broad range of ARGs was observed across multiple antibiotic classes, including macrolides, aminoglycosides, tetracyclines, phenicols, fluoroquinolones, sulfonamide-trimethoprim, beta-lactams, and MDR genes.\n\nThe results highlight the potential role of fresh food products in the widespread dissemination of Salmonella strains resistant to multiple antibiotics.", "doi": "10.1093/jambio/lxaf137", "pmid": "40459912", "labels": {"Clinical Genomics Link\u00f6ping": "Collaborative", "Clinical Genomics": "Collaborative", "NGI Short read": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pii", "key": "8155881"}], "notes": [], "created": "2025-06-04T12:59:02.555Z", "modified": "2025-09-08T06:59:27.016Z"}, {"entity": "publication", "iuid": "e9951e493ce143e8977c1f7de3cc015c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e9951e493ce143e8977c1f7de3cc015c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e9951e493ce143e8977c1f7de3cc015c"}}, "title": "Basal and exercise-induced expression of NLRP3 inflammasome-related components is increased in patients with chronic coronary syndrome.", "authors": [{"family": "Mahmood", "given": "Zeid", "initials": "Z"}, {"family": "B\u00e4ck", "given": "Maria", "initials": "M"}, {"family": "Leanderson", "given": "Per", "initials": "P"}, {"family": "Thune", "given": "Rebecka", "initials": "R"}, {"family": "Skoglund", "given": "Camilla", "initials": "C"}, {"family": "Jonasson", "given": "Lena", "initials": "L"}], "type": "journal article", "published": "2025-06-00", "journal": {"title": "Atherosclerosis", "issn": "1879-1484", "volume": "405", "pages": "119227", "issn-l": "0021-9150"}, "abstract": "NLRP3 inflammasome is considered a critical actor in the inflammatory process of coronary artery disease. Increased expression of NLRP3 inflammasome components has been reported in patients with acute coronary syndrome, but whether this persists beyond the acute phase is less known. We performed a prospective study to investigate whether basal and/or exercise-induced NLRP3 inflammasome components were elevated in patients with chronic coronary syndrome (CCS).\n\nPatients (n = 81) underwent exercise stress tests twice: 3-4 weeks and 3-6 months after a major coronary event, whereas controls (n = 30) performed it once. Concentrations of interleukin(IL)-18, IL-1Ra and IL-6 were measured before and 30 min after exercise. Genes related to NLRP3 inflammasome and NF\u03baB signaling pathways were measured in blood mononuclear cells before and after exercise. On the first visit, patients were prescribed an exercise-based cardiac rehabilitation program. Physical activity levels were reported on both visits.\n\nPatients were clinically stable and exhibited increased exercise capacity as well as increased self-reported physical activity between visits. Basal plasma levels of IL-18, as well as exercise-induced levels of IL-18 and IL-1Ra, were higher in patients compared with controls on both visits. Also, basal gene expression of NLRP3 was higher in patients, as were several NF\u03baB-related genes. After exercise, gene expression related to NLRP3 inflammasome activation, in particular P2RX7, was higher in patients on both visits.\n\nUp to 6 months after a coronary event, patients exhibited an increase in NLRP3 inflammasome-related components that was even more pronounced after acute exercise, compared with controls. The results indicate that a primed NLRP3 inflammasome system is maintained despite clinical stability and best available therapy, highlighting the need to further combat inflammation in patients with CCS.", "doi": "10.1016/j.atherosclerosis.2025.119227", "pmid": "40339359", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "S0021-9150(25)00125-X"}], "notes": [], "created": "2025-08-11T10:12:24.434Z", "modified": "2025-08-11T10:12:24.438Z"}, {"entity": "publication", "iuid": "dc00b746f211426db5e81bd6815bf3c5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/dc00b746f211426db5e81bd6815bf3c5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/dc00b746f211426db5e81bd6815bf3c5"}}, "title": "Rab7 inhibitor enhances stem cell differentiation into keratinocyte-like cells with anti-inflammatory properties.", "authors": [{"family": "Alghazali", "given": "Raghad", "initials": "R"}, {"family": "Tabebi", "given": "Mouna", "initials": "M"}, {"family": "Elmasry", "given": "Moustafa", "initials": "M"}, {"family": "El-Serafi", "given": "Ahmed", "initials": "A"}], "type": "journal article", "published": "2025-05-26", "journal": {"title": "Front Immunol", "issn": "1664-3224", "volume": "16", "pages": "1503007", "issn-l": "1664-3224"}, "abstract": "Management of difficult-to-heal skin wounds presents a significant clinical challenge, particularly when associated with inflammatory skin disorders. The differentiation of stem cells into keratinocyte-like cells has been explored as a potential regenerative therapy. Ras-related protein (Rab) 7, a key regulator of membrane trafficking, influences the activity of several growth factors. In this study, the competitive Rab7 inhibitor, CID-1067700, was investigated for the differentiation of adipose-derived stem cell into keratinocyte-like cells. This treatment upregulated several epidermal markers, including P63, cytokeratin 5 and 14 and filaggrin, while downregulated the stem cell marker, vimentin. Microarray data showed upregulation of the anti-inflammatory gene HMOX-1, coupled with the downregulation of various inflammation-related pathways, such as TNF, chemokine, AGE-RAGE and IL-17 signalling cascades, as well as cytokine-cytokine receptor interaction pathways. Gene set enrichment analysis predicted Ehmt2, an epigenetic regulator, to be the top activated upstream regulator, enhancing the transcriptional activity. Protein array analysis showed reduced secretion of several inflammatory cytokines, including IL-1\u03b1, IL-8, IL-17A, and IL-32, while enhancing the secretion of the epidermal growth factor. Our findings provide preliminary evidence that CID-1067700, as an additive to the differentiation media, not only enhances stem cell differentiation into keratinocyte-like cells, but also improves their anti-inflammatory properties. These combined regenerative and anti-inflammatory properties may offer significant therapeutic potential for patients with chronic skin wounds, particularly those with underlying inflammatory conditions.", "doi": "10.3389/fimmu.2025.1503007", "pmid": "40491919", "labels": {"Clinical Genomics Link\u00f6ping": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC12146274"}], "notes": [], "created": "2025-08-11T10:15:53.850Z", "modified": "2025-08-11T10:15:53.853Z"}, {"entity": "publication", "iuid": "12fa1b73f76d40158b12fc385a35aa1f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/12fa1b73f76d40158b12fc385a35aa1f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/12fa1b73f76d40158b12fc385a35aa1f"}}, "title": "Methodological aspects of investigating the resistome in pig farm environments.", "authors": [{"family": "Ladyhina", "given": "Valeriia", "initials": "V"}, {"family": "Rajala", "given": "Elisabeth", "initials": "E"}, {"family": "Sternberg-Lewerin", "given": "Susanna", "initials": "S"}, {"family": "Nasirzadeh", "given": "Leila", "initials": "L"}, {"family": "Bongcam-Rudloff", "given": "Erik", "initials": "E", "orcid": "0000-0002-1947-8288", "researcher": {"href": "https://publications.scilifelab.se/researcher/6970ca57259d498588ecf9e1ad28a9b0.json"}}, {"family": "Dicksved", "given": "Johan", "initials": "J"}], "type": "journal article", "published": "2025-02-13", "journal": {"title": "J Microbiol Methods", "issn": "1872-8359", "issn-l": null, "volume": "230-231", "issue": null, "pages": "107103"}, "abstract": "A typical One Health issue, antimicrobial resistance (AMR) development and its spread among people, animals, and the environment attracts significant research attention. The animal sector is one of the major contributors to the development and dissemination of AMR and accounts for more than 50 % of global antibiotics usage. The use of antibiotics exerts a selective pressure for resistant bacteria in the exposed microbiome, but many questions about the epidemiology of AMR in farm environments remain unanswered. This is connected to several methodological challenges and limitations, such as inconsistent sampling methods, complexity of farm environment samples and the lack of standardized protocols for sample collection, processing and bioinformatical analysis. In this project, we combined metagenomics and bioinformatics to optimise the methodology for reproducible research on the resistome in complex samples from the indoor farm environment. The work included optimizing sample collection, transportation, and storage, as well as DNA extraction, sequencing, and bioinformatic analysis, such as metagenome assembly and antibiotic resistance gene (ARG) detection. Our studies suggest that the current most optimal and cost-effective pipeline for ARG search should be based on Illumina sequencing of sock sample material at high depth (at least 25 M 250 bp PE for AMR gene families and 43 M for gene variants). We present a computational analysis utilizing MEGAHIT assembly to balance the identification of bacteria carrying ARGs with the potential loss of diversity and abundance of resistance genes. Our findings indicate that searching against multiple ARG databases is essential for detecting the highest diversity of ARGs.", "doi": "10.1016/j.mimet.2025.107103", "pmid": "39954816", "labels": {"Clinical Genomics Link\u00f6ping": "Collaborative", "Clinical Genomics": "Collaborative", "NGI Short read": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pii", "key": "S0167-7012(25)00019-3"}], "notes": [], "created": "2025-03-18T07:11:00.806Z", "modified": "2025-09-08T07:13:09.538Z"}, {"entity": "publication", "iuid": "fdd85dd6bc6544c9abccb2e0a6b9a4fa", "links": {"self": {"href": "https://publications.scilifelab.se/publication/fdd85dd6bc6544c9abccb2e0a6b9a4fa.json"}, "display": {"href": "https://publications.scilifelab.se/publication/fdd85dd6bc6544c9abccb2e0a6b9a4fa"}}, "title": "Modulation of biological activities in adipose derived stem cells by histone deacetylation.", "authors": [{"family": "Abdallah", "given": "Sallam", "initials": "S"}, {"family": "Tabebi", "given": "Mouna", "initials": "M", "orcid": "0000-0002-2873-161X", "researcher": {"href": "https://publications.scilifelab.se/researcher/285705c043f34b55826e7f33ab36a875.json"}}, {"family": "Qanadilo", "given": "Sawsan", "initials": "S"}, {"family": "Ali", "given": "Neserin", "initials": "N"}, {"family": "Wang", "given": "Jing", "initials": "J"}, {"family": "D'Arcy", "given": "P\u00e1draig", "initials": "P"}, {"family": "Zhong", "given": "Wen", "initials": "W", "orcid": "0000-0002-7422-6104", "researcher": {"href": "https://publications.scilifelab.se/researcher/a82c3b7da3b8472392d39ca5f6d5bedb.json"}}, {"family": "Sjoberg", "given": "Folke", "initials": "F"}, {"family": "Elmasry", "given": "Moustafa", "initials": "M"}, {"family": "El-Serafi", "given": "Ahmed", "initials": "A"}], "type": "journal article", "published": "2025-01-29", "journal": {"title": "Sci Rep", "issn": "2045-2322", "issn-l": "2045-2322", "volume": "15", "issue": "1", "pages": "3629"}, "abstract": "Difficult-to-heal wounds management accounts for about 4% of healthcare costs, highlighting the need for innovative solutions. Extracellular signals drive cell proliferation during tissue regeneration, while epigenetic mechanisms regulate stem cell homeostasis, differentiation, and skin repair. Exploring epigenetic regulation in adipose-derived stem cells (ADSCs) holds promise for improving skin injury treatments. We investigated the effects of histone deacetylase inhibitor (SAHA) on ADSCs to better understand its cellular and molecular impacts. ADSCs were treated with SAHA for 72 h, showing no change in cell viability at the studied concentrations. However, the expression of histone deacetylase decreased at 1000 nM, while the cell proliferation marker Ki-67 increased after SAHA treatment, as confirmed by immunofluorescence. CCND1 gene expression increased, whereas protein expression of the proliferating cell nuclear antigen (PCNA) decreased. Cell cycle analysis showed an increase in G2 phase in SAHA-treated cells. Microarray analysis revealed 74 upregulated and 40 downregulated differentially expressed genes, including upregulation of P53 targets, CDKN1A and MDM2. Proteomic analysis identified 631 upregulated and 823 downregulated proteins compared to the vehicle. Pathway enrichment analysis showed cell cycle, ATP-dependent chromatin remodeling and DNA processes were among the affected pathways. This study suggests SAHA modulates ADSCs' biological processes, highlighting its potential for skin regeneration.", "doi": "10.1038/s41598-024-84652-1", "pmid": "39880862", "labels": {"Clinical Genomics Link\u00f6ping": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-024-84652-1"}, {"db": "pmc", "key": "PMC11779964"}], "notes": [], "created": "2025-01-31T10:37:54.632Z", "modified": "2025-03-24T08:23:01.425Z"}, {"entity": "publication", "iuid": "7efe68cb12144989aaa7d3311aa2b137", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7efe68cb12144989aaa7d3311aa2b137.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7efe68cb12144989aaa7d3311aa2b137"}}, "title": "A landscape of X-inactivation during human T cell development.", "authors": [{"family": "Gylemo", "given": "Bj\u00f6rn", "initials": "B", "orcid": "0000-0001-5253-6737", "researcher": {"href": "https://publications.scilifelab.se/researcher/1e62e3eed2144dd0a2584a3cfbe7800a.json"}}, {"family": "Bensberg", "given": "Maike", "initials": "M", "orcid": "0000-0003-2395-6083", "researcher": {"href": "https://publications.scilifelab.se/researcher/afa6aec5136e46fd97981fa37b8c8295.json"}}, {"family": "Hennings", "given": "Viktoria", "initials": "V"}, {"family": "Lundqvist", "given": "Christina", "initials": "C", "orcid": "0000-0002-2256-4072", "researcher": {"href": "https://publications.scilifelab.se/researcher/10b339e6cc1f48f3a5f736201038ee59.json"}}, {"family": "Camponeschi", "given": "Alessandro", "initials": "A", "orcid": "0000-0002-6472-2438", "researcher": {"href": "https://publications.scilifelab.se/researcher/ccbaffafd6a24f4abed1e402219fa472.json"}}, {"family": "Goldmann", "given": "D\u00f3ra", "initials": "D"}, {"family": "Zhang", "given": "Huan", "initials": "H"}, {"family": "Selimovi\u0107-Pa\u0161i\u0107", "given": "Aida", "initials": "A"}, {"family": "Lentini", "given": "Antonio", "initials": "A", "orcid": "0000-0003-1239-5495", "researcher": {"href": "https://publications.scilifelab.se/researcher/e282901d24c64b16a540eff0d57776f4.json"}}, {"family": "Ekwall", "given": "Olov", "initials": "O", "orcid": "0000-0002-4506-9955", "researcher": {"href": "https://publications.scilifelab.se/researcher/2d7af11d7d30410d8fe5f3b5fbd0ba1d.json"}}, {"family": "Nestor", "given": "Colm E", "initials": "CE", "orcid": "0000-0001-5853-1769", "researcher": {"href": "https://publications.scilifelab.se/researcher/ca9fb12cf5754f36baf12f96f563ddb4.json"}}], "type": "journal article", "published": "2024-12-04", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "15", "issue": "1", "pages": "10527", "issn-l": "2041-1723"}, "abstract": "Females exhibit a more robust immune response to both self-antigens and non-self-antigens than males, resulting in a higher prevalence of autoimmune diseases but more effective responses against infection. Increased expression of X-linked immune genes in female T cells is thought to underlie this enhanced response. Here we isolate thymocytes from pediatric thymi of healthy males (46, XY), females (46, XX), a female with completely skewed X-chromosome inactivation (46, XX, cXCI) and a female with Turner syndrome (45, X0). Using whole exome sequencing, RNA sequencing and DNA methylation data, we present a sex-aware expression profile of T cell development and generate a high-resolution map of escape from X-chromosome inactivation (XCI). Unexpectedly, XCI is transcriptionally and epigenetically stable throughout T cell development, and is independent of expression of XIST, the lncRNA responsible for XCI initiation during early embryonic development. In thymocytes, several genes known to escape XCI are expressed from only one X-chromosome. Additionally, we further reveal that a second X-chromosome is dispensable for T cell development. Our study thus provides a high-resolution map of XCI during human development and suggests a re-evaluation of XCI in sex differences in T cell function.", "doi": "10.1038/s41467-024-54110-7", "pmid": "39632794", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11618795"}, {"db": "pii", "key": "10.1038/s41467-024-54110-7"}], "notes": [], "created": "2024-12-10T08:39:23.208Z", "modified": "2024-12-10T08:39:23.536Z"}, {"entity": "publication", "iuid": "763fcf7e521f425faf12b00bb5ef673b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/763fcf7e521f425faf12b00bb5ef673b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/763fcf7e521f425faf12b00bb5ef673b"}}, "title": "Duloxetine enhances PAX6 expression and suppresses innate immune responses in murine LPS-induced corneal inflammation.", "authors": [{"family": "Moustardas", "given": "Petros", "initials": "P"}, {"family": "Abbasi", "given": "Mojdeh", "initials": "M"}, {"family": "Javidjam", "given": "Dina", "initials": "D"}, {"family": "Asamoah", "given": "Cindy Saah", "initials": "CS"}, {"family": "Schweitzer-Chaput", "given": "Arnaud", "initials": "A"}, {"family": "Cisternino", "given": "Salvatore", "initials": "S"}, {"family": "Bremond-Gignac", "given": "Dominique", "initials": "D"}, {"family": "Aberdam", "given": "Daniel", "initials": "D"}, {"family": "Lagali", "given": "Neil", "initials": "N"}], "type": "journal article", "published": "2024-10-00", "journal": {"title": "Ocul Surf", "issn": "1937-5913", "volume": "34", "pages": "225-234", "issn-l": null}, "abstract": "PAX6 is a key regulator of eye development and epithelial homeostasis in the cornea. When deficient, chronic corneal inflammation, neovascularization and limbal stem cell deficiency can occur. Here we investigated the potential of duloxetine, a generic serotonin reuptake inhibitor that can upregulate PAX6 in vitro, for its in vivo activity in the context of corneal inflammation.\n\nDuloxetine tolerance was tested in a human limbal stem cell line and isogenic CRISPR-knockout PAX6+/- cells. C57BL/6-Wildtype mice were administered duloxetine eye drops at concentrations of 1 \u03bcM - 2 mM and tested for toxicity and corneal PAX6 expression. In LPS-induced corneal inflammation in mice, duloxetine's effect on PAX6 expression, corneal opacification and inflammatory responses were evaluated by in vivo corneal imaging, immunostaining, and whole-transcriptome microarray analysis.\n\nNo toxicity was observed in vitro for duloxetine concentrations up to 10\u03bc\u039c. In vivo, duloxetine drops were well-tolerated up to 50 \u03bcM. Duloxetine drops at 10\u03bc\u039c significantly upregulated PAX6 protein levels in the cornea by 30 % within 2 days. In the LPS model, duloxetine resulted in a sustained 33 % PAX6 protein upregulation in the cornea at 7 days, and in reduced opacity within 2 days, accompanied by a significant dampening of IL-17A signaling, neutrophil degranulation, microglial activation, macrophage markers, and MMP expression, despite non-significant changes in total inflammatory cell infiltration.\n\nShort-term administration of a repurposed generic drug, duloxetine, upregulates PAX6 protein levels in the cornea of mice and exerts an anti-inflammatory activity by dampening innate immune responses.", "doi": "10.1016/j.jtos.2024.08.008", "pmid": "39127390", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "S1542-0124(24)00086-7"}], "notes": [], "created": "2024-12-10T09:22:32.371Z", "modified": "2024-12-10T09:22:32.411Z"}, {"entity": "publication", "iuid": "e676be73f46b4ce4a645ce3228e182c0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e676be73f46b4ce4a645ce3228e182c0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e676be73f46b4ce4a645ce3228e182c0"}}, "title": "Multi-parametric atlas of the pre-metastatic liver for prediction of metastatic outcome in early-stage pancreatic cancer.", "authors": [{"family": "Bojmar", "given": "Linda", "initials": "L", "orcid": "0000-0002-2684-5824", "researcher": {"href": "https://publications.scilifelab.se/researcher/feea27777acd4f5eaad489ab7a7e2564.json"}}, {"family": "Zambirinis", "given": "Constantinos P", "initials": "CP", "orcid": "0000-0003-2740-3259", "researcher": {"href": "https://publications.scilifelab.se/researcher/ab745cf33a47430fb32228c645140e87.json"}}, {"family": "Hernandez", "given": "Jonathan M", "initials": "JM"}, {"family": "Chakraborty", "given": "Jayasree", "initials": "J"}, {"family": "Shaashua", "given": "Lee", "initials": "L"}, {"family": "Kim", "given": "Junbum", "initials": "J", "orcid": "0000-0001-7344-1593", "researcher": {"href": "https://publications.scilifelab.se/researcher/799d381beb2c485cb1e0d69ca66445e0.json"}}, {"family": "Johnson", "given": "Kofi Ennu", "initials": "KE"}, {"family": "Hanna", "given": "Samer", "initials": "S"}, {"family": "Askan", "given": "Gokce", "initials": "G"}, {"family": "Burman", "given": "Jonas", "initials": "J", "orcid": "0000-0002-0325-2321", "researcher": {"href": "https://publications.scilifelab.se/researcher/f5bb98855eae427999840ae66048132d.json"}}, {"family": "Ravichandran", "given": "Hiranmayi", "initials": "H"}, {"family": "Zheng", "given": "Jian", "initials": "J"}, {"family": "Jolissaint", "given": "Joshua S", "initials": "JS"}, {"family": "Srouji", "given": "Rami", "initials": "R"}, {"family": "Song", "given": "Yi", "initials": "Y"}, {"family": "Choubey", "given": "Ankur", "initials": "A", "orcid": "0000-0001-9930-0609", "researcher": {"href": "https://publications.scilifelab.se/researcher/bd4d30a4301442f5b21a7476ac1f133c.json"}}, {"family": "Kim", "given": "Han Sang", "initials": "HS"}, {"family": "Cioffi", "given": "Michele", "initials": "M"}, {"family": "van Beek", "given": "Elke", "initials": "E"}, {"family": "Sigel", "given": "Carlie", "initials": "C"}, {"family": "Jessurun", "given": "Jose", "initials": "J", "orcid": "0000-0002-1692-9880", "researcher": {"href": "https://publications.scilifelab.se/researcher/67a361a2ba714e22980ce23f1598f1ac.json"}}, {"family": "Velasco Riestra", "given": "Paulina", "initials": "P", "orcid": "0000-0001-7145-2619", "researcher": {"href": "https://publications.scilifelab.se/researcher/def1d743813f4288b6fdc3d39f1b7b71.json"}}, {"family": "Blomstrand", "given": "Hakon", "initials": "H", "orcid": "0000-0002-9845-1410", "researcher": {"href": "https://publications.scilifelab.se/researcher/4bdc03d870a641dba1d196f18cd6213b.json"}}, {"family": "J\u00f6nsson", "given": "Carolin", "initials": "C"}, {"family": "J\u00f6nsson", "given": "Anette", "initials": "A"}, {"family": "Lauritzen", "given": "Pernille", "initials": "P"}, {"family": "Buehring", "given": "Weston", "initials": "W"}, {"family": "Ararso", "given": "Yonathan", "initials": "Y"}, {"family": "Hernandez", "given": "Dylanne", "initials": "D"}, {"family": "Vinagolu-Baur", "given": "Jessica P", "initials": "JP"}, {"family": "Friedman", "given": "Madison", "initials": "M"}, {"family": "Glidden", "given": "Caroline", "initials": "C"}, {"family": "Firmenich", "given": "Laetitia", "initials": "L"}, {"family": "Lieberman", "given": "Grace", "initials": "G"}, {"family": "Mejia", "given": "Dianna L", "initials": "DL"}, {"family": "Nasar", "given": "Naaz", "initials": "N", "orcid": "0009-0004-2232-1590", "researcher": {"href": "https://publications.scilifelab.se/researcher/5bab35652b0e49238bef22e553ca88bb.json"}}, {"family": "Mutvei", "given": "Anders P", "initials": "AP"}, {"family": "Paul", "given": "Doru M", "initials": "DM"}, {"family": "Bram", "given": "Yaron", "initials": "Y"}, {"family": "Costa-Silva", "given": "Bruno", "initials": "B"}, {"family": "Basturk", "given": "Olca", "initials": "O", "orcid": "0000-0003-2747-1366", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7a077b4ce78438a8b5d2aec48e2928a.json"}}, {"family": "Boudreau", "given": "Nancy", "initials": "N"}, {"family": "Zhang", "given": "Haiying", "initials": "H"}, {"family": "Matei", "given": "Irina R", "initials": "IR", "orcid": "0000-0002-5712-8430", "researcher": {"href": "https://publications.scilifelab.se/researcher/c58b938e93a04c319f9802d51fe2f799.json"}}, {"family": "Hoshino", "given": "Ayuko", "initials": "A"}, {"family": "Kelsen", "given": "David", "initials": "D"}, {"family": "Sagi", "given": "Irit", "initials": "I"}, {"family": "Scherz", "given": "Avigdor", "initials": "A", "orcid": "0000-0002-8583-2169", "researcher": {"href": "https://publications.scilifelab.se/researcher/3005c7f7bd5e409ca6a1711018593b01.json"}}, {"family": "Scherz-Shouval", "given": "Ruth", "initials": "R", "orcid": "0000-0002-4570-121X", "researcher": {"href": "https://publications.scilifelab.se/researcher/338cbf96c5854c13bbcdecf6b1780527.json"}}, {"family": "Yarden", "given": "Yosef", "initials": "Y", "orcid": "0000-0003-4168-7884", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ef85228b8e6491c93c6f59e9167e399.json"}}, {"family": "Oren", "given": "Moshe", "initials": "M", "orcid": "0000-0003-4311-7172", "researcher": {"href": "https://publications.scilifelab.se/researcher/2c5a18704b294b68807208be700446b2.json"}}, {"family": "Egeblad", "given": "Mikala", "initials": "M"}, {"family": "Lewis", "given": "Jason S", "initials": "JS", "orcid": "0000-0001-7065-4534", "researcher": {"href": "https://publications.scilifelab.se/researcher/80e7e1eb00ac441eba915cfd5e10b2f2.json"}}, {"family": "Keshari", "given": "Kayvan", "initials": "K"}, {"family": "Grandgenett", "given": "Paul M", "initials": "PM"}, {"family": "Hollingsworth", "given": "Michael A", "initials": "MA", "orcid": "0000-0002-5255-8888", "researcher": {"href": "https://publications.scilifelab.se/researcher/098ff7ff95b04ef78d3b182d29fbb03b.json"}}, {"family": "Rajasekhar", "given": "Vinagolu K", "initials": "VK"}, {"family": "Healey", "given": "John H", "initials": "JH", "orcid": "0000-0002-0802-1186", "researcher": {"href": "https://publications.scilifelab.se/researcher/757777e590664028908d19152a79a8f2.json"}}, {"family": "Bj\u00f6rnsson", "given": "Bergthor", "initials": "B", "orcid": "0000-0001-9704-1260", "researcher": {"href": "https://publications.scilifelab.se/researcher/7f7e35d52e904a43b5405d4687c3871f.json"}}, {"family": "Simeone", "given": "Diane M", "initials": "DM", "orcid": "0000-0001-5142-3087", "researcher": {"href": "https://publications.scilifelab.se/researcher/d7a4fb23b1784cbba18e1bf5fb9bcbc7.json"}}, {"family": "Tuveson", "given": "David A", "initials": "DA"}, {"family": "Iacobuzio-Donahue", "given": "Christine A", "initials": "CA", "orcid": "0000-0002-4672-3023", "researcher": {"href": "https://publications.scilifelab.se/researcher/5983447412214f9fa76dd29b3b8ab89e.json"}}, {"family": "Bromberg", "given": "Jaqueline", "initials": "J", "orcid": "0000-0002-7957-9339", "researcher": {"href": "https://publications.scilifelab.se/researcher/c62643b6def54429a4fb2c5aad165307.json"}}, {"family": "Vincent", "given": "C Theresa", "initials": "CT"}, {"family": "O'Reilly", "given": "Eileen M", "initials": "EM", "orcid": "0000-0002-8076-9199", "researcher": {"href": "https://publications.scilifelab.se/researcher/80c72de771e14270adc275e2087f33fa.json"}}, {"family": "DeMatteo", "given": "Ronald P", "initials": "RP"}, {"family": "Balachandran", "given": "Vinod P", "initials": "VP", "orcid": "0000-0002-2956-223X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f7f8942d0a754765a8ddb21e7e1c9434.json"}}, {"family": "D'Angelica", "given": "Michael I", "initials": "MI"}, {"family": "Kingham", "given": "T Peter", "initials": "TP"}, {"family": "Allen", "given": "Peter J", "initials": "PJ"}, {"family": "Simpson", "given": "Amber L", "initials": "AL", "orcid": "0000-0002-4387-8417", "researcher": {"href": "https://publications.scilifelab.se/researcher/c03739a0c481451d911ed552dee75458.json"}}, {"family": "Elemento", "given": "Olivier", "initials": "O", "orcid": "0000-0002-8061-9617", "researcher": {"href": "https://publications.scilifelab.se/researcher/e30c36505e204e2f82c37ad44ac16bfe.json"}}, {"family": "Sandstr\u00f6m", "given": "Per", "initials": "P"}, {"family": "Schwartz", "given": "Robert E", "initials": "RE", "orcid": "0000-0002-5417-5995", "researcher": {"href": "https://publications.scilifelab.se/researcher/ea36e5f940ea4912a731165e477015a0.json"}}, {"family": "Jarnagin", "given": "William R", "initials": "WR"}, {"family": "Lyden", "given": "David", "initials": "D", "orcid": "0000-0003-0193-4131", "researcher": {"href": "https://publications.scilifelab.se/researcher/e8dd0eec61c047109d6923702915b91f.json"}}], "type": "journal article", "published": "2024-08-00", "journal": {"title": "Nat. Med.", "issn": "1546-170X", "volume": "30", "issue": "8", "pages": "2170-2180", "issn-l": "1078-8956"}, "abstract": "Metastasis occurs frequently after resection of pancreatic cancer (PaC). In this study, we hypothesized that multi-parametric analysis of pre-metastatic liver biopsies would classify patients according to their metastatic risk, timing and organ site. Liver biopsies obtained during pancreatectomy from 49 patients with localized PaC and 19 control patients with non-cancerous pancreatic lesions were analyzed, combining metabolomic, tissue and single-cell transcriptomics and multiplex imaging approaches. Patients were followed prospectively (median 3 years) and classified into four recurrence groups; early (<6 months after resection) or late (>6 months after resection) liver metastasis (LiM); extrahepatic metastasis (EHM); and disease-free survivors (no evidence of disease (NED)). Overall, PaC livers exhibited signs of augmented inflammation compared to controls. Enrichment of neutrophil extracellular traps (NETs), Ki-67 upregulation and decreased liver creatine significantly distinguished those with future metastasis from NED. Patients with future LiM were characterized by scant T cell lobular infiltration, less steatosis and higher levels of citrullinated H3 compared to patients who developed EHM, who had overexpression of interferon target genes (MX1 and NR1D1) and an increase of CD11B+ natural killer (NK) cells. Upregulation of sortilin-1 and prominent NETs, together with the lack of T cells and a reduction in CD11B+ NK cells, differentiated patients with early-onset LiM from those with late-onset LiM. Liver profiles of NED closely resembled those of controls. Using the above parameters, a machine-learning-based model was developed that successfully predicted the metastatic outcome at the time of surgery with 78% accuracy. Therefore, multi-parametric profiling of liver biopsies at the time of PaC diagnosis may determine metastatic risk and organotropism and guide clinical stratification for optimal treatment selection.", "doi": "10.1038/s41591-024-03075-7", "pmid": "38942992", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "mid", "key": "NIHMS2006571"}, {"db": "pmc", "key": "PMC11416063"}, {"db": "pii", "key": "10.1038/s41591-024-03075-7"}], "notes": [], "created": "2024-12-10T11:08:55.376Z", "modified": "2024-12-10T11:08:57.990Z"}, {"entity": "publication", "iuid": "efdb9aef03a14375a75ca6c15e600ae6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/efdb9aef03a14375a75ca6c15e600ae6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/efdb9aef03a14375a75ca6c15e600ae6"}}, "title": "A DNA Methylation Signature from Buccal Swabs to Identify Tuberculosis Infection.", "authors": [{"family": "Karlsson", "given": "Lovisa", "initials": "L", "orcid": "0000-0003-2704-1788", "researcher": {"href": "https://publications.scilifelab.se/researcher/9942f9d57c094401a1bb9b965f300092.json"}}, {"family": "\u00d6hrnberg", "given": "Isabelle", "initials": "I"}, {"family": "Sayyab", "given": "Shumaila", "initials": "S", "orcid": "0000-0002-6048-775X", "researcher": {"href": "https://publications.scilifelab.se/researcher/ab2cfb69351443089b25d19342879052.json"}}, {"family": "Mart\u00ednez-Enguita", "given": "David", "initials": "D", "orcid": "0000-0002-6363-6298", "researcher": {"href": "https://publications.scilifelab.se/researcher/7c31e0b73f7d414ea843d4b25b7547ec.json"}}, {"family": "Gustafsson", "given": "Mika", "initials": "M"}, {"family": "Espinoza", "given": "Patricia", "initials": "P"}, {"family": "M\u00e9ndez-Aranda", "given": "Melissa", "initials": "M"}, {"family": "Ugarte-Gil", "given": "Cesar", "initials": "C"}, {"family": "Diero", "given": "Lameck", "initials": "L"}, {"family": "Tonui", "given": "Ronald", "initials": "R"}, {"family": "Paues", "given": "Jakob", "initials": "J"}, {"family": "Lerm", "given": "Maria", "initials": "M", "orcid": "0000-0002-5092-9892", "researcher": {"href": "https://publications.scilifelab.se/researcher/6645c25a513f4bb8a24d11fd80c1b23d.json"}}], "type": "journal article", "published": "2024-07-04", "journal": {"title": "J. Infect. Dis.", "issn": "1537-6613", "issn-l": "0022-1899"}, "abstract": "Tuberculosis (TB) is amongst the largest infectious causes of death worldwide and there is a need for a time- and resource-effective diagnostic method. In this novel and exploratory study, we show the potential of using buccal swabs to collect human DNA and investigate the DNA methylation (DNAm) signatures as a diagnostic tool for TB.\n\nBuccal swabs were collected from pulmonary TB patients (n= 7), TB exposed (n= 7), and controls (n= 9) in Sweden. Using Illumina MethylationEPIC array the DNAm status was determined.\n\nWe identified 5644 significant differentially methylated CpG sites between the patients and controls. Performing the analysis on a validation cohort of samples collected in Kenya and Peru (patients, n=26; exposed, n=9; control, n=10) confirmed the DNAm signature. We identified a TB consensus disease module, significantly enriched in TB-associated genes. Lastly, we used machine learning to identify a panel of seven CpG sites discriminative for TB and developed a TB classifier. In the validation cohort the classifier performed with an AUC of 0.94, sensitivity of 0.92, and specificity of 1.\n\nIn summary, the result from this study shows clinical implications of using DNAm signatures from buccal swabs to explore new diagnostic strategies for TB.", "doi": "10.1093/infdis/jiae333", "pmid": "38962817", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "7705862"}], "notes": [], "created": "2024-12-10T08:21:23.003Z", "modified": "2024-12-10T08:27:56.963Z"}, {"entity": "publication", "iuid": "f9daa02387a8450ea37dc9ae719a92b7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f9daa02387a8450ea37dc9ae719a92b7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f9daa02387a8450ea37dc9ae719a92b7"}}, "title": "NOS2-derived low levels of NO drive psoriasis pathogenesis.", "authors": [{"family": "K\u00f6hler", "given": "Ines", "initials": "I"}, {"family": "Bivik Eding", "given": "Cecilia", "initials": "C"}, {"family": "Kasic", "given": "Nada-Katarina", "initials": "NK"}, {"family": "Verma", "given": "Deepti", "initials": "D"}, {"family": "Enerb\u00e4ck", "given": "Charlotta", "initials": "C", "orcid": "0000-0003-1769-3790", "researcher": {"href": "https://publications.scilifelab.se/researcher/492c35e3b7b44e23933cb0f91c721af3.json"}}], "type": "journal article", "published": "2024-06-26", "journal": {"title": "Cell Death Dis", "issn": "2041-4889", "volume": "15", "issue": "6", "pages": "449", "issn-l": "2041-4889"}, "abstract": "Psoriasis is an IL-23/Th17-mediated skin disorder with a strong genetic predisposition. The impact of its susceptibility gene nitric oxide synthase 2 (NOS2) remains unknown. Here, we demonstrate strong NOS2 mRNA expression in psoriatic epidermis, an effect that is IL-17 dependent. However, its complete translation to protein is prevented by the IL-17-induced miR-31 implying marginally upregulated NO levels in psoriatic skin. We demonstrate that lower levels of NO, as opposed to higher levels, increase keratinocyte proliferation and mediate IL-17 downstream effects. We hypothesized that the psoriatic phenotype may be alleviated by either eliminating or increasing cellular NO levels. In fact, using the imiquimod psoriasis mouse model, we found a profound impact on the psoriatic inflammation in both IMQ-treated NOS2 KO mice and wild-type mice treated with IMQ and the NO-releasing berdazimer gel. In conclusion, we demonstrate that IL-17 induces NOS2 and fine-tunes its translation towards a window of proinflammatory and hyperproliferative effects and identify NO donor therapy as a new treatment modality for psoriasis.", "doi": "10.1038/s41419-024-06842-z", "pmid": "38926337", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11208585"}, {"db": "pii", "key": "10.1038/s41419-024-06842-z"}], "notes": [], "created": "2024-12-10T09:26:46.550Z", "modified": "2024-12-10T09:26:46.618Z"}, {"entity": "publication", "iuid": "de6c277cbe7742e8a340e8361ab0ed75", "links": {"self": {"href": "https://publications.scilifelab.se/publication/de6c277cbe7742e8a340e8361ab0ed75.json"}, "display": {"href": "https://publications.scilifelab.se/publication/de6c277cbe7742e8a340e8361ab0ed75"}}, "title": "Tumor-matched and unmatched cancer associated fibroblasts exhibit differential effect on proliferation and FMOD and MMP9 gene expression in head and neck squamous cell carcinoma cells when cocultured in spheroids.", "authors": [{"family": "Rademaekers", "given": "Max", "initials": "M"}, {"family": "Johansson", "given": "Emil Oliver", "initials": "EO"}, {"family": "Johansson", "given": "Ellen", "initials": "E"}, {"family": "Roberg", "given": "Karin", "initials": "K", "orcid": "0000-0003-1208-9746", "researcher": {"href": "https://publications.scilifelab.se/researcher/7eb5c561930f4168ac912953147970b7.json"}}, {"family": "Wiechec", "given": "Emilia", "initials": "E", "orcid": "0000-0003-0270-9374", "researcher": {"href": "https://publications.scilifelab.se/researcher/03512a03bb1449d1a8b26e4c39054e4c.json"}}], "type": "journal article", "published": "2024-05-31", "journal": {"title": "Cancer Cell Int", "issn": "1475-2867", "volume": "24", "issue": "1", "pages": "190", "issn-l": "1475-2867"}, "abstract": "Cancer-associated fibroblasts (CAFs) are the major cellular component of the tumor microenvironment and are known to affect tumor growth and response to various treatments. This study was undertaken to investigate the crosstalk between tumor-matched or unmatched CAFs and head and neck squamous cell carcinoma (HNSCC) cells regarding tumor growth and treatment response.\n\nThree HNSCC cell lines (LK0412, LK0902 and LK0923), were cocultured in 2D or in 3D with their tumor-matched CAFs, site matched CAFs from other tumors or normal oral fibroblasts (NOFs). Cell proliferation was assessed as the amount of Ki67 positive cells/ spheroid area in formalin-fixed- paraffin-embedded 3D spheroids stained with Ki67 antibody. Viability after seven days of cisplatin treatment was measured with CellTiter-Glo 3D Viability Assay. The mRNA expression of CAF-associated markers (ACTA2, COL1A2, FAP, PDGFR\u03b1, PDGFR\u03b2, PDPN, POSTN and S100A4) in CAFs before and after coculture with tumor cells as well as mRNA expression of CAF-induced genes (MMP1, MMP9 and FMOD) in tumor cells separated from CAFs after co-culture was measured with RT-qPCR. The expression of selected protein biomarkers was validated with immunohistochemistry based on previous mRNA expression results.\n\nThe proliferation of the LK0412 and LK0902 tumor spheroids varied significantly when cocultured with different CAFs and NOFs as shown by Ki-67 positive cells. RT\u2012qPCR analysis revealed different molecular profile of the analyzed HNSCC-derived CAFs concerning the expression of CAF-associated markers. The interaction between CAFs and HNSCC cells was more pronounced after coculture with unmatched CAFs as shown by changes in mRNA expression pattern of CAF-specific markers. Additionally, the unmatched CAFs significantly upregulated the mRNA expression of MMP1, MMP9 and FMOD in tumor cells compared to tumor-matched CAFs.\n\nOur results indicate that tumor-matched CAFs are unique for each tumor and affect the proliferation and the gene/protein expression of tumor cells in a distinct manner. The interaction between tumor unmatched CAFs and HNSCC cells in the tumor spheroids is associated with significant changes in the mRNA expression of CAF-specific markers and significant increases in FMOD and MMP9 in tumor cells compared to when cocultured with tumor-matched CAFs. Taken together, our results show how important the selection of CAFs is to get a reliable in vitro model that mimics the patients' tumor.", "doi": "10.1186/s12935-024-03388-0", "pmid": "38822309", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11143562"}, {"db": "pii", "key": "10.1186/s12935-024-03388-0"}], "notes": [], "created": "2024-12-10T08:33:32.474Z", "modified": "2024-12-10T08:33:32.694Z"}, {"entity": "publication", "iuid": "8d5556642a834f52ac6644b809e230e1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8d5556642a834f52ac6644b809e230e1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8d5556642a834f52ac6644b809e230e1"}}, "title": "Exhaustive identification of genome-wide binding events of transcriptional regulators.", "authors": [{"family": "Nordin", "given": "Anna", "initials": "A", "orcid": "0000-0002-5868-4797", "researcher": {"href": "https://publications.scilifelab.se/researcher/f2e576298b274e1b8eba78f3f6df759f.json"}}, {"family": "Pagella", "given": "Pierfrancesco", "initials": "P", "orcid": "0000-0001-6912-0957", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e4bd6708be24fd9a4370a91e8101a96.json"}}, {"family": "Zambanini", "given": "Gianluca", "initials": "G", "orcid": "0000-0003-1275-6027", "researcher": {"href": "https://publications.scilifelab.se/researcher/37637bc1358a4928b87eff29af644efe.json"}}, {"family": "Cant\u00f9", "given": "Claudio", "initials": "C", "orcid": "0000-0003-1547-5415", "researcher": {"href": "https://publications.scilifelab.se/researcher/c005c54c7c5845c39c413cd2d8062aaa.json"}}], "type": "journal article", "published": "2024-04-24", "journal": {"title": "Nucleic Acids Res.", "issn": "1362-4962", "volume": "52", "issue": "7", "pages": "e40", "issn-l": "0305-1048"}, "abstract": "Genome-wide binding assays aspire to map the complete binding pattern of gene regulators. Common practice relies on replication-duplicates or triplicates-and high stringency statistics to favor false negatives over false positives. Here we show that duplicates and triplicates of CUT&RUN are not sufficient to discover the entire activity of transcriptional regulators. We introduce ICEBERG (Increased Capture of Enrichment By Exhaustive Replicate aGgregation), a pipeline that harnesses large numbers of CUT&RUN replicates to discover the full set of binding events and chart the line between false positives and false negatives. We employed ICEBERG to map the full set of H3K4me3-marked regions, the targets of the co-factor \u03b2-catenin, and those of the transcription factor TBX3, in human colorectal cancer cells. The ICEBERG datasets allow benchmarking of individual replicates, comparing the performance of peak calling and replication approaches, and expose the arbitrary nature of strategies to identify reproducible peaks. Instead of a static view of genomic targets, ICEBERG establishes a spectrum of detection probabilities across the genome for a given factor, underlying the intrinsic dynamicity of its mechanism of action, and permitting to distinguish frequent from rare regulation events. Finally, ICEBERG discovered instances, undetectable with other approaches, that underlie novel mechanisms of colorectal cancer progression.", "doi": "10.1093/nar/gkae180", "pmid": "38499482", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11040144"}, {"db": "pii", "key": "7631395"}], "notes": [], "created": "2024-12-10T08:31:19.039Z", "modified": "2024-12-10T08:31:19.142Z"}, {"entity": "publication", "iuid": "331439f75b96458c8eb2c119329d0ac9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/331439f75b96458c8eb2c119329d0ac9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/331439f75b96458c8eb2c119329d0ac9"}}, "title": "MicroRNA-155 mediates multiple gene regulations pertinent to the role of human adipose-derived mesenchymal stem cells in skin regeneration.", "authors": [{"family": "Shahin", "given": "Hady", "initials": "H"}, {"family": "Belcastro", "given": "Luigi", "initials": "L"}, {"family": "Das", "given": "Jyotirmoy", "initials": "J"}, {"family": "Perdiki Grigoriadi", "given": "Marina", "initials": "M"}, {"family": "Saager", "given": "Rolf B", "initials": "RB"}, {"family": "Steinvall", "given": "Ingrid", "initials": "I"}, {"family": "Sj\u00f6berg", "given": "Folke", "initials": "F"}, {"family": "Olofsson", "given": "Pia", "initials": "P"}, {"family": "Elmasry", "given": "Moustafa", "initials": "M"}, {"family": "El-Serafi", "given": "Ahmed T", "initials": "AT"}], "type": "journal article", "published": "2024-03-18", "journal": {"title": "Front Bioeng Biotechnol", "issn": "2296-4185", "volume": "12", "pages": "1328504", "issn-l": null}, "abstract": "Introduction: The role of Adipose-derived mesenchymal stem cells (AD-MSCs) in skin wound healing remains to be fully characterized. This study aims to evaluate the regenerative potential of autologous AD-MSCs in a non-healing porcine wound model, in addition to elucidate key miRNA-mediated epigenetic regulations that underlie the regenerative potential of AD-MSCs in wounds. Methods: The regenerative potential of autologous AD-MSCs was evaluated in porcine model using histopathology and spatial frequency domain imaging. Then, the correlations between miRNAs and proteins of AD-MSCs were evaluated using an integration analysis in primary human AD-MSCs in comparison to primary human keratinocytes. Transfection study of AD-MSCs was conducted to validate the bioinformatics data. Results: Autologous porcine AD-MSCs improved wound epithelialization and skin properties in comparison to control wounds. We identified 26 proteins upregulated in human AD-MSCs, including growth and angiogenic factors, chemokines and inflammatory cytokines. Pathway enrichment analysis highlighted cell signalling-associated pathways and immunomodulatory pathways. miRNA-target modelling revealed regulations related to genes encoding for 16 upregulated proteins. miR-155-5p was predicted to regulate Fibroblast growth factor 2 and 7, C-C motif chemokine ligand 2 and Vascular cell adhesion molecule 1. Transfecting human AD-MSCs cell line with anti-miR-155 showed transient gene silencing of the four proteins at 24 h post-transfection. Discussion: This study proposes a positive miR-155-mediated gene regulation of key factors involved in wound healing. The study represents a promising approach for miRNA-based and cell-free regenerative treatment for difficult-to-heal wounds. The therapeutic potential of miR-155 and its identified targets should be further explored in-vivo.", "doi": "10.3389/fbioe.2024.1328504", "pmid": "38562669", "labels": {"Clinical Genomics Link\u00f6ping": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10982420"}, {"db": "pii", "key": "1328504"}], "notes": [], "created": "2024-12-10T08:36:50.057Z", "modified": "2024-12-10T08:36:58.034Z"}, {"entity": "publication", "iuid": "f7eae2dfcf724ddfb922545eaf6c0d2e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f7eae2dfcf724ddfb922545eaf6c0d2e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f7eae2dfcf724ddfb922545eaf6c0d2e"}}, "title": "Prognostic value of hypoxia-responsive gene expression profile in patients diagnosed with head and neck squamous cell carcinoma.", "authors": [{"family": "Matic", "given": "Natasa", "initials": "N"}, {"family": "Pettersson", "given": "Lina", "initials": "L"}, {"family": "Sellebjerg", "given": "Felicia", "initials": "F"}, {"family": "Lindberg", "given": "Lina", "initials": "L"}, {"family": "Roberg", "given": "Karin", "initials": "K"}, {"family": "Wiechec", "given": "Emilia", "initials": "E"}], "type": "journal article", "published": "2024-01-00", "journal": {"title": "Transl Oncol", "issn": "1936-5233", "volume": "39", "pages": "101841", "issn-l": null}, "abstract": "Head and neck squamous cell carcinoma (HNSCC) is a disease associated with a severe mortality and high risk of distant metastasis and local recurrence. Currently, surgery and radiotherapy are the main treatment modes, however, therapeutic efficacy of radiotherapy is linked to tumor resistance. Hypoxia has been shown to affect outcome of radiotherapy in HNSCC patients. The aim of this study was to verify the expression of the previously identified hypoxia-responsive genes (CA9, CASP14, LOX, GLUT3, SERPINE1, AREG, EREG, CCNB1 and KIF14) in HNSCC patient material as well as assess their prognostic potential. Tumor biopsies obtained before start of radiotherapy from 32 HNSCC patients classified as responders or non-responders were investigated in this study. The mRNA expression was quantified using RT-qPCR. The mRNA expression of CA9, SERPINE1 and KIF14 was significantly higher in the analyzed patient material compared with the non-cancerous oral tissue. Moreover, the KIF14 mRNA expression was significantly higher in the responder group compared to non-responders. Further studies demonstrated that knockdown of KIF14 reverses its radiosensitizing capability. Additionally, low expression of KIF14 mRNA correlated with significantly shorter OS (overall survival). In conclusion, our results suggest that KIF14 might be a useful prognostic and predictive marker in HNSCC.", "doi": "10.1016/j.tranon.2023.101841", "pmid": "38016355", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10687700"}, {"db": "pii", "key": "S1936-5233(23)00227-9"}], "notes": [], "created": "2024-12-10T08:26:54.973Z", "modified": "2024-12-10T08:27:58.359Z"}, {"entity": "publication", "iuid": "f807081bedf7425abb72ad6d25b172ad", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f807081bedf7425abb72ad6d25b172ad.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f807081bedf7425abb72ad6d25b172ad"}}, "title": "Modified N-acyl-L-homoserine lactone compounds abrogate Las-dependent quorum-sensing response in human pathogen Pseudomonas aeruginosa.", "authors": [{"family": "Ballante", "given": "Flavio", "initials": "F"}, {"family": "Turkina", "given": "Maria V", "initials": "MV"}, {"family": "Ntzouni", "given": "Maria", "initials": "M"}, {"family": "Magnusson", "given": "Karl-Eric", "initials": "KE"}, {"family": "Vikstr\u00f6m", "given": "Elena", "initials": "E"}], "type": "journal article", "published": "2023-10-16", "journal": {"title": "Front Mol Biosci", "issn": "2296-889X", "volume": "10", "pages": "1264773", "issn-l": "2296-889X"}, "abstract": "Quorum sensing (QS) is a mode of cell-cell communication that bacteria use to sense population density and orchestrate collective behaviors. The common opportunistic human pathogen Pseudomonas aeruginosa employs QS to regulate a large set of genes involved in virulence and host-pathogen interactions. The Las circuit positioned on the top of the QS hierarchy in P. aeruginosa makes use of N-acyl-L-homoserine lactones (AHLs) as signal molecules, like N-3-oxo-dodecanoyl-L-homoserine lactone (3O-C12-HSL). Disabling QS circuits by certain small-molecule compounds, known as quorum-sensing inhibitors (QSIs), has been proposed as a strategy to attenuate bacterial pathogenicity. In this study, four new AHL analogs were designed by incorporating a tert-butoxycarbonyl Boc group in amide and \u03b2-keto (3-oxo) moiety. Compounds were evaluated on a molecular and phenotypic basis as a QSI using the screening strategy linked to the assignment of the Las QS system in P. aeruginosa. Using a LasR-based bioreporter, we found that the compounds decreased LasR-controlled light activity and competed efficiently with natural 3O-C12-HSL. The compounds reduced the production of the cognate 3O-C12-HSL and certain virulence traits, like total protease activity, elastase activity, pyocyanin production, and extracellular DNA release. Furthermore, a quantitative proteomic approach was used to study the effect of the compounds on QS-regulated extracellular proteins. Among the four compounds tested, one of them showed the most significant difference in the appearance of the 3O-C12-HSL-responsive reference proteins related to QS communication and virulence, i.e., a distinct activity as a QSI. Moreover, by combining experimental data with computational chemistry, we addressed the effect of LasR protein flexibility on docking precision and assessed the advantage of using a multi-conformational docking procedure for binding mode prediction of LasR modulators. Thus, the four new AHL compounds were tested for their interaction with the AHL-binding site in LasR to identify the key interferences with the activity of LasR. Our study provides further insight into molecular features that are required for small-molecule modulation of LasR-dependent QS communication in P. aeruginosa. This should facilitate rational design of the next generation of antivirulence tools to study and manipulate QS-controlled fitness in bacteria and, thereby, handle bacterial infections in a new way.", "doi": "10.3389/fmolb.2023.1264773", "pmid": "37908228", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service", "Chemical Biology Consortium Sweden": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10613653"}, {"db": "pii", "key": "1264773"}], "notes": [], "created": "2023-11-24T11:35:39.234Z", "modified": "2025-10-17T13:04:27.537Z"}, {"entity": "publication", "iuid": "258b76aac8194ccb8fe5921fc83b2bcb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/258b76aac8194ccb8fe5921fc83b2bcb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/258b76aac8194ccb8fe5921fc83b2bcb"}}, "title": "Genome-wide DNA methylation profiling in Lyme neuroborreliosis reveals altered methylation patterns of HLA genes.", "authors": [{"family": "Henningsson", "given": "Anna J", "initials": "AJ", "orcid": "0000-0002-9315-8901", "researcher": {"href": "https://publications.scilifelab.se/researcher/ab7eaa1dcf394cf3a866f08992117e62.json"}}, {"family": "Hellberg", "given": "Sandra", "initials": "S", "orcid": "0000-0002-8713-7434", "researcher": {"href": "https://publications.scilifelab.se/researcher/725a263c9f804deba79bf73459fa709b.json"}}, {"family": "Lerm", "given": "Maria", "initials": "M", "orcid": "0000-0002-5092-9892", "researcher": {"href": "https://publications.scilifelab.se/researcher/6645c25a513f4bb8a24d11fd80c1b23d.json"}}, {"family": "Sayyab", "given": "Shumaila", "initials": "S", "orcid": "0000-0002-6048-775X", "researcher": {"href": "https://publications.scilifelab.se/researcher/ab2cfb69351443089b25d19342879052.json"}}], "type": "journal article", "published": "2023-10-12", "journal": {"title": "J. Infect. Dis.", "issn": "1537-6613", "issn-l": "0022-1899"}, "abstract": "Lyme neuroborreliosis (LNB) is a complex neuroinflammatory disorder caused by Borrelia burgdorferi transmitted through tick bites. Epigenetic alterations, specifically DNA methylation (DNAm), could play a role in the host immune response during infection. In this study, we present the first genome-wide analysis of DNAm in PBMCs from LNB and non-LNB patients. Using a network-based approach, highlighted HLA genes at the core of these DNAm changes, which were found to be enriched in immune-related pathways. These findings shed light on the role of epigenetic modifications in the LNB pathogenesis that should be confirmed and further expanded upon in future studies.", "doi": "10.1093/infdis/jiad451", "pmid": "37824827", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "7310834"}], "notes": [], "created": "2023-12-03T06:01:39.490Z", "modified": "2023-12-03T06:01:39.627Z"}, {"entity": "publication", "iuid": "c1ee33b53e234983b5dc0bb7365058df", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c1ee33b53e234983b5dc0bb7365058df.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c1ee33b53e234983b5dc0bb7365058df"}}, "title": "Selected \u03b2-glucans act as immune-training agents by improving anti-mycobacterial activity in human macrophages - a pilot study.", "authors": [{"family": "Braian", "given": "Clara", "initials": "C"}, {"family": "Karlsson", "given": "Lovisa", "initials": "L"}, {"family": "Das", "given": "Jyotirmoy", "initials": "J"}, {"family": "Lerm", "given": "Maria", "initials": "M"}], "type": "news", "published": "2023-09-21", "journal": {"title": "J Innate Immun", "issn": "1662-8128", "volume": "15", "issue": "1", "pages": "751-764", "issn-l": "1662-811X"}, "abstract": "Epigenetic reprogramming of innate immune cells by \u03b2-glucan in a process called trained immunity, leads to an enhanced host response to a secondary infection. \u03b2-glucans are structural components of plants, algae, fungi and bacteria and thus recognized as non-self by human macrophages. We selected the \u03b2-glucans curdlan from Alcaligenes faecalis, WGP dispersible from Saccharomyces cerevisiae, and \u03b2-glucan-rich culture supernatant of Alternaria and investigated whether they could produce trained immunity effects leading to an increased control of virulent Mycobacterium tuberculosis. We observed a significant M. tuberculosis growth-reduction in macrophages trained with curdlan and Alternaria, which also correlated with increased IL-6 and IL-1\u03b2 release. WGP dispersible-trained macrophages were stratified into 'non responders' and 'responders', according to their ability to control M. tuberculosis, with 'responders' producing higher IL-6 levels. The addition of neutrophils to infected macrophage cultures further enhanced macrophage control of virulent M. tuberculosis, but not in a stimuli-dependent manner. Pathway enrichment analysis of DNA methylome data also highlighted hypomethylation of genes in pathways associated with signaling and cellular reorganization and motility, and 'responders' to WGP-training were enriched in the interferon-gamma signaling pathway. This study adds evidence that certain \u03b2-glucans show promise as immune training agents.", "doi": "10.1159/000533873", "pmid": "37734337", "labels": {"Clinical Genomics Link\u00f6ping": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10616672"}, {"db": "pii", "key": "000533873"}], "notes": [], "created": "2023-12-03T06:08:06.478Z", "modified": "2023-12-03T06:08:06.481Z"}, {"entity": "publication", "iuid": "84abbf194070412ba40948f5df29984d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/84abbf194070412ba40948f5df29984d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/84abbf194070412ba40948f5df29984d"}}, "title": "Epigenetic modifications appear in the human placenta following anxiety and depression during pregnancy.", "authors": [{"family": "Martinez", "given": "Cristina A", "initials": "CA"}, {"family": "Marteinsdottir", "given": "Ina", "initials": "I"}, {"family": "Josefsson", "given": "Ann", "initials": "A"}, {"family": "Sydsj\u00f6", "given": "Gunilla", "initials": "G"}, {"family": "Theodorsson", "given": "Elvar", "initials": "E"}, {"family": "Rodriguez-Martinez", "given": "Heriberto", "initials": "H"}], "type": "journal article", "published": "2023-09-07", "journal": {"title": "Placenta", "issn": "1532-3102", "volume": "140", "pages": "72-79", "issn-l": null}, "abstract": "The future health of the offspring can be influenced by longstanding maternal anxiety and depression disorders during pregnancy. The present study aimed to explore the effect of psychiatric disorders during pregnancy on placental epigenetics.\n\nWe measured DNA methylation patterns in term-placentas of women either suffering longstanding anxiety and depression symptoms (Index group, with overt symptoms), or a healthy population (Control, none/only mild symptoms). Whole genome DNA methylation profiling was performed using the TruSeq\u00ae Methyl Capture EPIC Library Prep Kit (Illumina, San Diego, CA, USA) for library preparation and NGS technology for genomic DNA sequencing.\n\nThe results of high-throughput DNA methylation analysis revealed that the Index group had differential DNA methylation at epigenome-wide significance (p < 0.05) in 226 genes in the placenta. Targeted enrichment analyses identified hypermethylation of genes associated with psychiatric disorders (BRINP1, PUM1), and ion homeostasis (COMMD1), among others. The ECM (extracellular matrix)-receptor interaction pathway was significantly dysregulated in the Index group compared to the Control. In addition, DNA methylation/mRNA integration analyses revealed that four genes with key roles in neurodevelopment and other important processes (EPB41L4B, BMPR2, KLHL18, and UBAP2) were dysregulated at both, DNA methylation and transcriptome levels in the Index group compared to Control.\n\nThe presented results increase our understanding of how maternal psychiatric disorders may affect the newborn through placental differential epigenome, suggesting DNA methylation status as a biomarker when aiming to design new preventive techniques and interventions.", "doi": "10.1016/j.placenta.2023.07.298", "pmid": "37549439", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "S0143-4004(23)00455-1"}], "notes": [], "created": "2023-12-03T05:45:44.214Z", "modified": "2023-12-03T05:45:44.234Z"}, {"entity": "publication", "iuid": "47413d73c5cb40fbaa2da5d27272dd26", "links": {"self": {"href": "https://publications.scilifelab.se/publication/47413d73c5cb40fbaa2da5d27272dd26.json"}, "display": {"href": "https://publications.scilifelab.se/publication/47413d73c5cb40fbaa2da5d27272dd26"}}, "title": "Differential DNA Methylation of MicroRNA-Encoding Genes in Psoriatic Epidermis Highlights the Wnt Pathway.", "authors": [{"family": "Verma", "given": "Deepti", "initials": "D"}, {"family": "Kasic", "given": "Nada-Katarina", "initials": "NK"}, {"family": "Jeppsson", "given": "Freja", "initials": "F"}, {"family": "Eding", "given": "Cecilia Bivik", "initials": "CB"}, {"family": "\u0141ysiak", "given": "Ma\u0142gorzata", "initials": "M"}, {"family": "Fekri", "given": "Shora Zamani", "initials": "SZ"}, {"family": "Das", "given": "Jyotirmoy", "initials": "J"}, {"family": "Enerb\u00e4ck", "given": "Charlotta", "initials": "C"}], "type": "journal article", "published": "2023-08-00", "journal": {"title": "J. Invest. Dermatol.", "issn": "1523-1747", "volume": "143", "issue": "8", "pages": "1594-1597.e14", "issn-l": "0022-202X"}, "abstract": null, "doi": "10.1016/j.jid.2023.01.031", "pmid": "36858310", "labels": {"Clinical Genomics Link\u00f6ping": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0022-202X(23)00104-5"}], "notes": [], "created": "2023-12-03T05:52:00.066Z", "modified": "2023-12-03T05:52:00.070Z"}, {"entity": "publication", "iuid": "6cb03b0394e244b58c41d816ba85a68c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6cb03b0394e244b58c41d816ba85a68c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6cb03b0394e244b58c41d816ba85a68c"}}, "title": "Domain landscapes of somatic NF1 mutations in pheochromocytoma and paraganglioma.", "authors": [{"family": "Tabebi", "given": "Mouna", "initials": "M"}, {"family": "Frikha", "given": "Fakher", "initials": "F"}, {"family": "Volpe", "given": "Massimiliano", "initials": "M"}, {"family": "Gimm", "given": "Oliver", "initials": "O"}, {"family": "S\u00f6derkvist", "given": "Peter", "initials": "P"}], "type": "journal article", "published": "2023-07-01", "journal": {"title": "Gene", "issn": "1879-0038", "volume": "872", "pages": "147432", "issn-l": "0378-1119"}, "abstract": "Pheochromocytoma and paraganglioma (PPGL), are rare neuroendocrine tumors arising from the adrenal medulla and extra-adrenal paraganglia, respectively. Up to about 60% are explained by germline or somatic mutations in one of the major known susceptibility genes e.g., inNF1,RET,VHL, SDHx,MAXandHRAS. Targeted Next Generation Sequencing was performed in 14 sporadic tumors using a panel including 26 susceptibility genes to characterize the mutation profile. A total of 6 germline and 8 somatic variants were identified. The most frequent somatic mutations were found in NF1(36%), four have not been reported earlier in PCC or PGL. Gene expression profile analysis showed that NF1 mutated tumors are classified into RTK3 subtype, cluster 2, with a high expression of genes associated with chromaffin cell differentiation, and into a RTK2 subtype, cluster 2, as well with overexpression of genes associated with cortisol biosynthesis. On the other hand, by analyzing the entire probe set on the array and TCGA data, ALDOC was found as the most significantly down regulated gene in NF1-mutated tumors compared to NF1-wild-type. Differential gene expression analysis showed a significant difference between Nt - and Ct-NF1 domains in mutated tumors probably engaging different cellular pathways. Notably, we had a metastatic PCC with a Ct-NF1 frameshift mutation and when performing protein docking analysis, Ct-NF1 showed an interaction with Nt-FAK suggesting their involvement in cell adhesion and cell growth. These results show that depending on the location of the NF1-mutation different pathways are activated in PPGLs. Further studies are required to clarify their clinical significance.", "doi": "10.1016/j.gene.2023.147432", "pmid": "37062455", "labels": {"Clinical Genomics Link\u00f6ping": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "S0378-1119(23)00273-1"}], "notes": [], "created": "2023-12-03T06:09:50.777Z", "modified": "2023-12-03T06:09:50.781Z"}, {"entity": "publication", "iuid": "554898676dc943d6b283e73b339115d8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/554898676dc943d6b283e73b339115d8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/554898676dc943d6b283e73b339115d8"}}, "title": "Mating modifies the expression of crucial oxidative-reductive transcripts in the pig oviductal sperm reservoir: is the female ensuring sperm survival?", "authors": [{"family": "\u00c1lvarez-Rodr\u00edguez", "given": "Manuel", "initials": "M"}, {"family": "Roca", "given": "Jordi", "initials": "J"}, {"family": "Mart\u00ednez", "given": "Emilio A", "initials": "EA"}, {"family": "Rodr\u00edguez-Mart\u00ednez", "given": "Heriberto", "initials": "H"}], "type": "journal article", "published": "2023-06-07", "journal": {"title": "Front Endocrinol (Lausanne)", "issn": "1664-2392", "volume": "14", "pages": "1042176", "issn-l": null}, "abstract": "Mating induces large changes in the female genital tract, warranting female homeostasis and immune preparation for pregnancy, including the preservation of crucial oxidative status among its pathways. Being highly susceptible to oxidative stress, sperm survival and preserved function depend on the seminal plasma, a protection that is removed during sperm handling but also after mating when spermatozoa enter the oviduct. Therefore, it is pertinent to consider that the female sperm reservoir takes up this protection, providing a suitable environment for sperm viability. These aspects have not been explored despite the increasing strategies in modulating the female status through diet control and nutritional supplementation.\n\nTo test the hypothesis that mating modifies the expression of crucial oxidative-reductive transcripts across the entire pig female genital tract (cervix to infundibulum) and, particularly in the sperm reservoir at the utero-tubal junction, before ovulation, a period dominated by estrogen stimulation of ovarian as well as of seminal origin.\n\nThe differential expression of estrogen (ER) and progesterone (PR) receptors and of 59 oxidative-reductive transcripts were studied using a species-specific microarray platform, in specific segments of the peri-ovulatory sow reproductive tract in response to mating.\n\nMating induced changes along the entire tract, with a conspicuous downregulation of both ER and PR and an upregulation of superoxide dismutase 1 (SOD1), glutaredoxin (GLRX3), and peroxiredoxin 1 and 3 (PRDX1, PRDX3), among other NADH Dehydrogenase Ubiquinone Flavoproteins, in the distal uterus segment. These changes perhaps helped prevent oxidative stress in the area adjacent to the sperm reservoir at the utero-tubal junction. Concomitantly, there were a downregulation of catalase (CAT) and NADH dehydrogenase (ubiquinone) oxidoreductases 1 beta subcomplex, subunit 1 (NDUFB1) in the utero-tubal junction alongside an overall downregulation of CAT, SOD1, and PRDX3 in the ampullar and infundibulum segments.\n\nNatural mating is an inducer of changes in the expression of female genes commanding antioxidant enzymes relevant for sperm survival during sperm transport, under predominant estrogen influence through the bloodstream and semen. The findings could contribute to the design of new therapeutics for the female to improve oxidative-reductive balance.", "doi": "10.3389/fendo.2023.1042176", "pmid": "37351104", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10282951"}], "notes": [], "created": "2023-12-03T05:45:45.911Z", "modified": "2023-12-03T05:45:45.931Z"}, {"entity": "publication", "iuid": "f662260585b8490d92cb95f40eb405ca", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f662260585b8490d92cb95f40eb405ca.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f662260585b8490d92cb95f40eb405ca"}}, "title": "Stress-sensitive dynamics of miRNAs and Elba1 in Drosophila embryogenesis.", "authors": [{"family": "\u00d6rkenby", "given": "Lovisa", "initials": "L", "orcid": "0000-0002-6015-7240", "researcher": {"href": "https://publications.scilifelab.se/researcher/c0a1d51d61264021818dd484cc6ddaff.json"}}, {"family": "Skog", "given": "Signe", "initials": "S", "orcid": "0000-0002-7590-8326", "researcher": {"href": "https://publications.scilifelab.se/researcher/c0cb5b0f3f694a10abf049f9e9c298e3.json"}}, {"family": "Ekman", "given": "Helen", "initials": "H", "orcid": "0000-0002-0181-6170", "researcher": {"href": "https://publications.scilifelab.se/researcher/7dff0e6e3025446084e6fc3e0254abe7.json"}}, {"family": "Gozzo", "given": "Alessandro", "initials": "A", "orcid": "0000-0002-6466-627X", "researcher": {"href": "https://publications.scilifelab.se/researcher/37245c697b3c4e119f91a9f44f47607a.json"}}, {"family": "Kugelberg", "given": "Unn", "initials": "U"}, {"family": "Ramesh", "given": "Rashmi", "initials": "R", "orcid": "0000-0003-3685-7893", "researcher": {"href": "https://publications.scilifelab.se/researcher/08615ef9bb444dea8b40973374177ae6.json"}}, {"family": "Magadi", "given": "Srivathsa", "initials": "S", "orcid": "0000-0002-7926-5970", "researcher": {"href": "https://publications.scilifelab.se/researcher/61353f2ecb17431594018661b201f8da.json"}}, {"family": "Zambanini", "given": "Gianluca", "initials": "G", "orcid": "0000-0003-1275-6027", "researcher": {"href": "https://publications.scilifelab.se/researcher/37637bc1358a4928b87eff29af644efe.json"}}, {"family": "Nordin", "given": "Anna", "initials": "A", "orcid": "0000-0002-5868-4797", "researcher": {"href": "https://publications.scilifelab.se/researcher/f2e576298b274e1b8eba78f3f6df759f.json"}}, {"family": "Cant\u00fa", "given": "Claudio", "initials": "C", "orcid": "0000-0003-1547-5415", "researcher": {"href": "https://publications.scilifelab.se/researcher/c005c54c7c5845c39c413cd2d8062aaa.json"}}, {"family": "N\u00e4tt", "given": "Daniel", "initials": "D", "orcid": "0000-0001-9182-9401", "researcher": {"href": "https://publications.scilifelab.se/researcher/6af95d8800274851babd3c3ecae29c55.json"}}, {"family": "\u00d6st", "given": "Anita", "initials": "A", "orcid": "0000-0003-0547-1904", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7a222183b264e4b828a38c322a4090f.json"}}], "type": "journal article", "published": "2023-05-09", "journal": {"title": "Mol. Syst. Biol.", "issn": "1744-4292", "volume": "19", "issue": "5", "pages": "e11148", "issn-l": "1744-4292"}, "abstract": "Early-life stress can result in life-long effects that impact adult health and disease risk, but little is known about how such programming is established and maintained. Here, we show that such epigenetic memories can be initiated in the Drosophila embryo before the major wave of zygotic transcription, and higher-order chromatin structures are established. An early short heat shock results in elevated levels of maternal miRNA and reduced levels of a subgroup of zygotic genes in stage 5 embryos. Using a Dicer-1 mutant, we show that the stress-induced decrease in one of these genes, the insulator-binding factor Elba1, is dependent on functional miRNA biogenesis. Reduction in Elba1 correlates with the upregulation of early developmental genes and promotes a sustained weakening of heterochromatin in the adult fly as indicated by an increased expression of the PEV wm4h reporter. We propose that maternal miRNAs, retained in response to an early embryonic heat shock, shape the subsequent de novo heterochromatin establishment that occurs during early development via direct or indirect regulation of some of the earliest expressed genes, including Elba1.", "doi": "10.15252/msb.202211148", "pmid": "36938679", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10167479"}], "notes": [], "created": "2023-12-03T05:45:48.775Z", "modified": "2023-12-03T05:45:49.133Z"}, {"entity": "publication", "iuid": "4e17395031e840d18135c925fc1214da", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4e17395031e840d18135c925fc1214da.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4e17395031e840d18135c925fc1214da"}}, "title": "methylR: a graphical interface for comprehensive DNA methylation array data analysis.", "authors": [{"family": "Volpe", "given": "Massimiliano", "initials": "M", "orcid": "0000-0003-4184-5264", "researcher": {"href": "https://publications.scilifelab.se/researcher/72a3bf9590054279985a2fbb287ef8ce.json"}}, {"family": "Das", "given": "Jyotirmoy", "initials": "J", "orcid": "0000-0002-5649-4658", "researcher": {"href": "https://publications.scilifelab.se/researcher/ebcbc4237c1c48aeb6bdd446fd8d2c8a.json"}}], "type": "journal article", "published": "2023-04-03", "journal": {"title": "Bioinformatics", "issn": "1367-4811", "volume": "39", "issue": "4", "issn-l": "1367-4803"}, "abstract": "DNA methylation analysis using arrays is a widely used method in research and clinical studies to study Epigenetics. Although several packages have been published to incur the results, most of them require a deep computational knowledge to perform the analysis. To resolve the limitation and to offer an easily accessible solution for researchers, we developed methylR a graphical tool that can analyze not only the raw data but also performs different downstream analyses with a few mouse clicks.\n\nWe used standard and established open-source published packages or pipelines in methylR. We evaluated a publicly available dataset and compared the published results with those obtained with our tool. We implemented eight downstream analysis modules that can perform multidimensional analyses to pathway enrichment. Although the main application is designed for Illumina DNA methylation array data analysis, we made the accessory modules suitable for other kinds of data analysis as well.\n\nFreely available at Github: https://github.com/JD2112/methylr; Webserver: https://methylr.research.liu.se.", "doi": "10.1093/bioinformatics/btad184", "pmid": "37039839", "labels": {"Clinical Genomics Link\u00f6ping": "Technology development", "Clinical Genomics": "Technology development"}, "xrefs": [{"db": "pmc", "key": "PMC10125902"}, {"db": "pii", "key": "7114023"}], "notes": [], "created": "2023-12-03T06:05:10.029Z", "modified": "2023-12-03T06:05:10.070Z"}, {"entity": "publication", "iuid": "055792514ea54dbaa757467d73ba8d5b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/055792514ea54dbaa757467d73ba8d5b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/055792514ea54dbaa757467d73ba8d5b"}}, "title": "Immune-related microRNAs in breast milk and their relation to regulatory T cells in breastfed children.", "authors": [{"family": "Ahlberg", "given": "Emelie", "initials": "E", "orcid": "0000-0002-7119-6114", "researcher": {"href": "https://publications.scilifelab.se/researcher/676300abed2d4948ba3e3937ca6c6e4a.json"}}, {"family": "Mart\u00ed", "given": "Magal\u00ed", "initials": "M", "orcid": "0000-0002-1927-4656", "researcher": {"href": "https://publications.scilifelab.se/researcher/6aad3e4e37b042c7a38e9f4717998410.json"}}, {"family": "Govindaraj", "given": "Dhanapal", "initials": "D", "orcid": "0000-0003-1303-8254", "researcher": {"href": "https://publications.scilifelab.se/researcher/8b619a8a42d74fb997fe908813c115ec.json"}}, {"family": "Severin", "given": "Elisabet", "initials": "E"}, {"family": "Duch\u00e9n", "given": "Karel", "initials": "K", "orcid": "0000-0002-0570-8898", "researcher": {"href": "https://publications.scilifelab.se/researcher/5784b47b03734e5292d3d0501a98a65c.json"}}, {"family": "Jenmalm", "given": "Maria C", "initials": "MC", "orcid": "0000-0002-2117-5366", "researcher": {"href": "https://publications.scilifelab.se/researcher/bf1f485192744e0c95ccecdb5471b577.json"}}, {"family": "Ting\u00f6", "given": "Lina", "initials": "L", "orcid": "0000-0002-2482-9281", "researcher": {"href": "https://publications.scilifelab.se/researcher/e2efcdbe9af6460290bf64e5d9843fcc.json"}}], "type": "randomized controlled trial", "published": "2023-04-00", "journal": {"title": "Pediatr Allergy Immunol", "issn": "1399-3038", "volume": "34", "issue": "4", "pages": "e13952", "issn-l": "0905-6157"}, "abstract": "The immunomodulatory capacity of breast milk may partially be mediated by microRNAs (miRNA), small RNA molecules that regulate gene expression on a post-transcriptional level and are hypothesized to be involved in modulation of immunological pathways. Here, we evaluate the expression of immune-related miRNAs in breast milk after pre- and postnatal supplementation with Limosilactobacillus reuteri and omega-3 (\u03c9-3) polyunsaturated fatty acids (PUFAs), and the association to infant regulatory T cell (Treg) frequencies.\n\nOne-hundred and twenty women included in a double-blind, randomized, placebo-controlled allergy intervention trial received L. reuteri and/or \u03c9-3 PUFAs daily from gestational week 20. Using Taqman qPCR, 24 miRNAs were analyzed from breast milk obtained at birth (colostrum) and after 3 months (mature milk) of lactation. The proportion of activated and resting Treg cells were analyzed in infant blood using flow cytometry at 6, 12, and 24 months.\n\nRelative expression changed significantly over the lactation period for most of the miRNAs; however, the expression was not significantly influenced by any of the supplements. Colostrum miR-181a-3p correlated with resting Treg cell frequencies at 6 months. Colostrum miR-148a-3p and let-7d-3p correlated with the frequencies of activated Treg cells at 24 months, as did mature milk miR-181a-3p and miR-181c-3p.\n\nMaternal supplementation with L. reuteri and \u03c9-3 PUFAs did not significantly affect the relative miRNA expression in breast milk. Interestingly, some of the miRNAs correlate with Treg subpopulations in the breastfed children, supporting the hypothesis that breast milk miRNAs could be important in infant immune regulation.\n\nClinicalTrials.gov-ID: NCT01542970.", "doi": "10.1111/pai.13952", "pmid": "37102392", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "ClinicalTrials.gov", "key": "NCT01542970"}], "notes": [], "created": "2023-12-03T05:45:47.197Z", "modified": "2023-12-03T05:45:47.376Z"}, {"entity": "publication", "iuid": "b5b1cf7954344c1788417ce16b90c590", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b5b1cf7954344c1788417ce16b90c590.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b5b1cf7954344c1788417ce16b90c590"}}, "title": "miRNome and Proteome Profiling of Human Keratinocytes and Adipose Derived Stem Cells Proposed miRNA-Mediated Regulations of Epidermal Growth Factor and Interleukin 1-Alpha.", "authors": [{"family": "Shahin", "given": "Hady", "initials": "H", "orcid": "0000-0003-3894-6849", "researcher": {"href": "https://publications.scilifelab.se/researcher/19bc3853696c459980e4d71f4ba66687.json"}}, {"family": "Abdallah", "given": "Sallam", "initials": "S"}, {"family": "Das", "given": "Jyotirmoy", "initials": "J", "orcid": "0000-0002-5649-4658", "researcher": {"href": "https://publications.scilifelab.se/researcher/ebcbc4237c1c48aeb6bdd446fd8d2c8a.json"}}, {"family": "He", "given": "Weihai", "initials": "W"}, {"family": "El-Serafi", "given": "Ibrahim", "initials": "I", "orcid": "0000-0002-0463-1518", "researcher": {"href": "https://publications.scilifelab.se/researcher/9b3cc7696eeb4c82ac5115342730d11c.json"}}, {"family": "Steinvall", "given": "Ingrid", "initials": "I"}, {"family": "Sj\u00f6berg", "given": "Folke", "initials": "F"}, {"family": "Elmasry", "given": "Moustafa", "initials": "M"}, {"family": "El-Serafi", "given": "Ahmed T", "initials": "AT"}], "type": "journal article", "published": "2023-03-04", "journal": {"title": "Int J Mol Sci", "issn": "1422-0067", "volume": "24", "issue": "5", "issn-l": null}, "abstract": "Wound healing is regulated by complex crosstalk between keratinocytes and other cell types, including stem cells. In this study, a 7-day direct co-culture model of human keratinocytes and adipose-derived stem cells (ADSCs) was proposed to study the interaction between the two cell types, in order to identify regulators of ADSCs differentiation toward the epidermal lineage. As major mediators of cell communication, miRNome and proteome profiles in cell lysates of cultured human keratinocytes and ADSCs were explored through experimental and computational analyses. GeneChip\u00ae miRNA microarray, identified 378 differentially expressed miRNAs; of these, 114 miRNAs were upregulated and 264 miRNAs were downregulated in keratinocytes. According to miRNA target prediction databases and the Expression Atlas database, 109 skin-related genes were obtained. Pathway enrichment analysis revealed 14 pathways including vesicle-mediated transport, signaling by interleukin, and others. Proteome profiling showed a significant upregulation of the epidermal growth factor (EGF) and Interleukin 1-alpha (IL-1\u03b1) compared to ADSCs. Integrated analysis through cross-matching the differentially expressed miRNA and proteins suggested two potential pathways for regulations of epidermal differentiation; the first is EGF-based through the downregulation of miR-485-5p and miR-6765-5p and/or the upregulation of miR-4459. The second is mediated by IL-1\u03b1 overexpression through four isomers of miR-30-5p and miR-181a-5p.", "doi": "10.3390/ijms24054956", "pmid": "36902387", "labels": {"Clinical Genomics Link\u00f6ping": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10002856"}, {"db": "pii", "key": "ijms24054956"}], "notes": [], "created": "2023-12-03T05:51:58.814Z", "modified": "2023-12-03T06:11:02.288Z"}, {"entity": "publication", "iuid": "8949ae798885446eb4b442de770a73dd", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8949ae798885446eb4b442de770a73dd.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8949ae798885446eb4b442de770a73dd"}}, "title": "Nuclear and mitochondrial DNA alterations in pheochromocytomas and paragangliomas, and their potential treatment.", "authors": [{"family": "Tabebi", "given": "Mouna", "initials": "M", "orcid": "0000-0002-2873-161X", "researcher": {"href": "https://publications.scilifelab.se/researcher/285705c043f34b55826e7f33ab36a875.json"}}, {"family": "S\u00f6derkvist", "given": "Peter", "initials": "P"}, {"family": "Gimm", "given": "Oliver", "initials": "O"}], "type": "journal article", "published": "2023-01-01", "journal": {"title": "Endocr. Relat. Cancer", "issn": "1479-6821", "volume": "30", "issue": "1", "issn-l": "1351-0088"}, "abstract": "Mitochondrial DNA (mtDNA) alterations have been reported in different types of cancers and are suggested to play important roles in cancer development and metastasis. However, there is little information about its involvement in pheochromocytomas and paragangliomas (PCCs/PGLs) formation. PCCs and PGLs are rare endocrine tumors of the chromaffin cells in the adrenal medulla and extra-adrenal paraganglia that can synthesize and secrete catecholamines. Over the last 3 decades, the genetic background of about 60% of PCCs/PGLs involving nuclear DNA alterations has been determined. Recently, a study showed that mitochondrial alterations can be found in around 17% of the remaining PCCs/PGLs. In this review, we summarize recent knowledge regarding both nuclear and mitochondrial alterations and their involvement in PCCs/PGLs. We also provide brief insights into the genetics and the molecular pathways associated with PCCs/PGLs and potential therapeutical targets.", "doi": "10.1530/ERC-22-0217", "pmid": "36219865", "labels": {"Clinical Genomics Link\u00f6ping": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "ERC-22-0217"}], "notes": [], "created": "2023-12-03T06:08:55.703Z", "modified": "2023-12-03T06:08:55.727Z"}, {"entity": "publication", "iuid": "4a77304d7f6442b9a79bb65a57066699", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4a77304d7f6442b9a79bb65a57066699.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4a77304d7f6442b9a79bb65a57066699"}}, "title": "A new cut&run low volume-urea (LoV-U) protocol optimized for transcriptional co-factors uncovers Wnt/b-catenin tissue-specific genomic targets.", "authors": [{"family": "Zambanini", "given": "Gianluca", "initials": "G"}, {"family": "Nordin", "given": "Anna", "initials": "A"}, {"family": "Jonasson", "given": "Mattias", "initials": "M"}, {"family": "Pagella", "given": "Pierfrancesco", "initials": "P", "orcid": "0000-0001-6912-0957", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e4bd6708be24fd9a4370a91e8101a96.json"}}, {"family": "Cant\u00f9", "given": "Claudio", "initials": "C", "orcid": "0000-0003-1547-5415", "researcher": {"href": "https://publications.scilifelab.se/researcher/c005c54c7c5845c39c413cd2d8062aaa.json"}}], "type": "journal article", "published": "2022-11-10", "journal": {"title": "Development", "issn": "1477-9129", "issn-l": "0950-1991"}, "abstract": "Upon WNT/b-catenin pathway activation, stabilized b-catenin travels to the nucleus where it associates with the TCF/LEF transcription factors, constitutively bound to genomic Wnt Responsive Elements (WREs), to activate target gene transcription. Discovering the binding profile of b-catenin is therefore required to unambiguously assign direct targets of WNT signaling. Cleavage Under Targets and Release Using Nuclease (CUT&RUN) has emerged as prime technique for mapping the binding profile of DNA-interacting proteins. Here we present a modified version of CUT&RUN, named LoV-U (Low Volume and Urea), that enables the robust and reproducible generation of b-catenin binding profiles, uncovering direct WNT/\u03b2-catenin target genes in human cells, as well as in cells isolated from developing mouse tissues. CUT&RUN-LoV-U outperforms original CUT&RUN when targeting co-factors that do not bind the DNA, can profile all classes of chromatin regulators, and is well suited for simultaneous processing of several samples. We submit that the application of our protocol will allow the detection of the complex system of tissue-specific WNT/\u03b2-catenin target genes, together with other non-DNA-binding transcriptional regulators that act downstream of ontogenetically fundamental signaling cascades.", "doi": "10.1242/dev.201124", "pmid": "36355069", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "281294"}], "notes": [], "created": "2022-12-01T14:06:22.162Z", "modified": "2022-12-01T14:06:22.264Z"}, {"entity": "publication", "iuid": "f9d6b4d3118c473da25126f8a55ce15b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f9d6b4d3118c473da25126f8a55ce15b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f9d6b4d3118c473da25126f8a55ce15b"}}, "title": "Case report: Two sisters with a germline CHEK2 variant and distinct endocrine neoplasias.", "authors": [{"family": "Vallera", "given": "Raphaelle D", "initials": "RD"}, {"family": "Ding", "given": "Yanli", "initials": "Y"}, {"family": "Hatanpaa", "given": "Kimmo J", "initials": "KJ"}, {"family": "Bishop", "given": "Justin A", "initials": "JA"}, {"family": "Mirfakhraee", "given": "Sasan", "initials": "S"}, {"family": "Alli", "given": "Abdel A", "initials": "AA"}, {"family": "Tevosian", "given": "Sergei G", "initials": "SG"}, {"family": "Tabebi", "given": "Mouna", "initials": "M"}, {"family": "Gimm", "given": "Oliver", "initials": "O"}, {"family": "S\u00f6derkvist", "given": "Peter", "initials": "P"}, {"family": "Estrada-Zuniga", "given": "Cynthia", "initials": "C"}, {"family": "Dahia", "given": "Patricia L M", "initials": "PLM"}, {"family": "Ghayee", "given": "Hans K", "initials": "HK"}], "type": "case reports", "published": "2022-11-07", "journal": {"title": "Front Endocrinol (Lausanne)", "issn": "1664-2392", "volume": "13", "pages": "1024108", "issn-l": null}, "abstract": "Genetic testing has become the standard of care for many disease states. As a result, physicians treating patients who have tumors often rely on germline genetic testing results for making clinical decisions. Cases of two sisters carrying a germline CHEK2 variant are highlighted whereby possible other genetic drivers were discovered on tumor analysis. CHEK2 (also referred to as CHK2) loss of function has been firmly associated with breast cancer development. In this case report, two siblings with a germline CHEK2 mutation also had distinct endocrine tumors. Pituitary adenoma and pancreatic neuroendocrine tumor (PNET) was found in the first sibling and pheochromocytoma (PCC) discovered in the second sibling. Although pituitary adenomas, PNETs, and PCC have been associated with NF1 gene mutations, the second sister with a PCC did have proven germline CHEK2 with a pathogenic somatic NF1 mutation. We highlight the clinical point that unless the tumor is sequenced, the real driver mutation that is causing the patient's tumor may remain unknown.", "doi": "10.3389/fendo.2022.1024108", "pmid": "36440216", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9682564"}], "notes": [], "created": "2022-12-01T14:11:20.222Z", "modified": "2022-12-01T14:11:20.225Z"}, {"entity": "publication", "iuid": "5a0eec7e1de34b63b052c1ec086abb9e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5a0eec7e1de34b63b052c1ec086abb9e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5a0eec7e1de34b63b052c1ec086abb9e"}}, "title": "The oncogenic transcription factor FOXQ1 is a differential regulator of Wnt target genes.", "authors": [{"family": "Pizzolato", "given": "Giulia", "initials": "G", "orcid": "0000-0002-0776-456X", "researcher": {"href": "https://publications.scilifelab.se/researcher/ef73508c139e455d9f5378f6e7c30728.json"}}, {"family": "Moparthi", "given": "Lavanya", "initials": "L", "orcid": "0000-0002-6030-3084", "researcher": {"href": "https://publications.scilifelab.se/researcher/c2207da5d7d34dd2a8def5239eaf351d.json"}}, {"family": "S\u00f6derholm", "given": "Simon", "initials": "S"}, {"family": "Cant\u00f9", "given": "Claudio", "initials": "C"}, {"family": "Koch", "given": "Stefan", "initials": "S", "orcid": "0000-0003-3579-4229", "researcher": {"href": "https://publications.scilifelab.se/researcher/74c70c1aa5624edfb9d9b36ce7bef947.json"}}], "type": "journal article", "published": "2022-10-01", "journal": {"title": "J. Cell. Sci.", "issn": "1477-9137", "volume": "135", "issue": "19", "issn-l": "0021-9533"}, "abstract": "The forkhead box transcription factor FOXQ1 contributes to the pathogenesis of carcinomas. In colorectal cancers, FOXQ1 promotes tumour metastasis by inducing epithelial-to-mesenchymal transition (EMT) of cancer cells. FOXQ1 may exacerbate cancer by activating the oncogenic Wnt/\u03b2-catenin signalling pathway. However, the role of FOXQ1 in the Wnt pathway remains to be resolved. Here, we report that FOXQ1 is an activator of Wnt-induced transcription and regulator of \u03b2-catenin target gene expression. Upon Wnt pathway activation, FOXQ1 synergises with the \u03b2-catenin nuclear complex to boost the expression of major Wnt targets. In parallel, we find that FOXQ1 controls the differential expression of various Wnt target genes in a \u03b2-catenin-independent manner. Using RNA sequencing of colorectal cancer cell lines, we show that Wnt signalling and FOXQ1 converge on a transcriptional programme linked to EMT and cell migration. Additionally, we demonstrate that FOXQ1 occupies Wnt-responsive elements in \u03b2-catenin target gene promoters and recruits a similar set of co-factors to the \u03b2-catenin-associated transcription factor Tcf7l1. Taken together, our results indicate a multifaceted role of FOXQ1 in Wnt/\u03b2-catenin signalling, which may drive the metastasis of colorectal cancers.", "doi": "10.1242/jcs.260082", "pmid": "36124643", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "277173"}], "notes": [], "created": "2022-12-01T14:08:05.597Z", "modified": "2022-12-01T14:08:05.811Z"}, {"entity": "publication", "iuid": "8f99faf4497b42b4bf664ee35621c290", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8f99faf4497b42b4bf664ee35621c290.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8f99faf4497b42b4bf664ee35621c290"}}, "title": "Implementing precision medicine in a regionally organized healthcare system in Sweden.", "authors": [{"family": "Fioretos", "given": "Thoas", "initials": "T"}, {"family": "Wirta", "given": "Valtteri", "initials": "V", "orcid": "0000-0003-3811-5439", "researcher": {"href": "https://publications.scilifelab.se/researcher/cba024b2e3c347f6b981922d984ad2d6.json"}}, {"family": "Cavelier", "given": "Lucia", "initials": "L"}, {"family": "Berglund", "given": "Eva", "initials": "E"}, {"family": "Friedman", "given": "Mikaela", "initials": "M", "orcid": "0000-0002-5483-9771", "researcher": {"href": "https://publications.scilifelab.se/researcher/f1507c81499748d8bf0ee1eb647a37d4.json"}}, {"family": "Akhras", "given": "Michael", "initials": "M"}, {"family": "Botling", "given": "Johan", "initials": "J"}, {"family": "Ehrencrona", "given": "Hans", "initials": "H", "orcid": "0000-0002-5589-3622", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b89608a8ce941c3b9911630b4ff9720.json"}}, {"family": "Engstrand", "given": "Lars", "initials": "L"}, {"family": "Helenius", "given": "Gisela", "initials": "G"}, {"family": "Fagerqvist", "given": "Therese", "initials": "T"}, {"family": "Gisselsson", "given": "David", "initials": "D", "orcid": "0000-0002-0301-426X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3653582762b14f9a9ad2fe6aba511115.json"}}, {"family": "Gruvberger-Saal", "given": "Sofia", "initials": "S", "orcid": "0000-0002-8478-9920", "researcher": {"href": "https://publications.scilifelab.se/researcher/70ffd3b67d32420e841027d5ff630b4c.json"}}, {"family": "Gyllensten", "given": "Ulf", "initials": "U", "orcid": "0000-0002-6316-3355", "researcher": {"href": "https://publications.scilifelab.se/researcher/e8739f0f42c44019ab88a49db350a4f2.json"}}, {"family": "Heidenblad", "given": "Markus", "initials": "M", "orcid": "0000-0002-0668-2263", "researcher": {"href": "https://publications.scilifelab.se/researcher/b49a0816fc794c27a25b34731e8ca7bf.json"}}, {"family": "H\u00f6glund", "given": "Kina", "initials": "K"}, {"family": "Jacobsson", "given": "Bo", "initials": "B", "orcid": "0000-0001-5079-2374", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd6968816ded4a50b1029ee3f4afbeed.json"}}, {"family": "Johansson", "given": "Maria", "initials": "M"}, {"family": "Johansson", "given": "\u00c5sa", "initials": "\u00c5", "orcid": "0000-0002-2915-4498", "researcher": {"href": "https://publications.scilifelab.se/researcher/76265c54961046e99bdb0439f9ae1d34.json"}}, {"family": "Soller", "given": "Maria Johansson", "initials": "MJ"}, {"family": "Landstr\u00f6m", "given": "Mar\u00e9ne", "initials": "M", "orcid": "0000-0001-6737-7230", "researcher": {"href": "https://publications.scilifelab.se/researcher/c2f02fcfb1c1497d81a6f343bc0e6928.json"}}, {"family": "Larsson", "given": "P\u00e4r", "initials": "P"}, {"family": "Levin", "given": "Lars-\u00c5ke", "initials": "L"}, {"family": "Lindstrand", "given": "Anna", "initials": "A", "orcid": "0000-0003-0806-5602", "researcher": {"href": "https://publications.scilifelab.se/researcher/07f3e6152da043d38c7a81974fcf8c23.json"}}, {"family": "Lovmar", "given": "Lovisa", "initials": "L"}, {"family": "Lyander", "given": "Anna", "initials": "A"}, {"family": "Melin", "given": "Malin", "initials": "M"}, {"family": "Nordgren", "given": "Ann", "initials": "A", "orcid": "0000-0003-3285-4281", "researcher": {"href": "https://publications.scilifelab.se/researcher/08e74c6ddc27493696beca0883027cdd.json"}}, {"family": "Nordmark", "given": "Gunnel", "initials": "G", "orcid": "0000-0002-3829-7431", "researcher": {"href": "https://publications.scilifelab.se/researcher/188fda53498740dbb007441cc94bb1ad.json"}}, {"family": "M\u00f6lling", "given": "Paula", "initials": "P"}, {"family": "Palmqvist", "given": "Lars", "initials": "L", "orcid": "0000-0001-9274-360X", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e50c0057dcb47f39e085b16580806c2.json"}}, {"family": "Palmqvist", "given": "Richard", "initials": "R"}, {"family": "Repsilber", "given": "Dirk", "initials": "D"}, {"family": "Sikora", "given": "Per", "initials": "P"}, {"family": "Stenmark", "given": "Bianca", "initials": "B"}, {"family": "S\u00f6derkvist", "given": "Peter", "initials": "P", "orcid": "0000-0001-9867-8706", "researcher": {"href": "https://publications.scilifelab.se/researcher/c1fc163b9a08421180f7f235af3897f4.json"}}, {"family": "Stranneheim", "given": "Henrik", "initials": "H"}, {"family": "Strid", "given": "Tobias", "initials": "T"}, {"family": "Wheelock", "given": "Craig E", "initials": "CE", "orcid": "0000-0002-8113-0653", "researcher": {"href": "https://publications.scilifelab.se/researcher/a3cd2b99e3e9486ba41030c809a48c51.json"}}, {"family": "Wadelius", "given": "Mia", "initials": "M", "orcid": "0000-0002-6368-2622", "researcher": {"href": "https://publications.scilifelab.se/researcher/ec07b9869a1f4b77b734c5dc567dc630.json"}}, {"family": "Wedell", "given": "Anna", "initials": "A"}, {"family": "Edsj\u00f6", "given": "Anders", "initials": "A"}, {"family": "Rosenquist", "given": "Richard", "initials": "R"}], "type": "letter", "published": "2022-10-00", "journal": {"title": "Nat. Med.", "issn": "1546-170X", "issn-l": "1078-8956", "volume": "28", "issue": "10", "pages": "1980-1982"}, "abstract": null, "doi": "10.1038/s41591-022-01963-4", "pmid": "36123428", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics Gothenburg": "Collaborative", "Clinical Genomics Ume\u00e5": "Service", "Clinical Genomics Uppsala": "Collaborative", "Clinical Genomics Stockholm": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "10.1038/s41591-022-01963-4"}], "notes": [], "created": "2022-12-01T14:09:51.971Z", "modified": "2023-11-22T21:50:50.052Z"}, {"entity": "publication", "iuid": "e6a735bf3fb24992925a2c4b5aafb847", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e6a735bf3fb24992925a2c4b5aafb847.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e6a735bf3fb24992925a2c4b5aafb847"}}, "title": "Methylation associated with long- or short-term survival in glioblastoma patients from the Nordic phase 3 trial.", "authors": [{"family": "\u0141ysiak", "given": "Ma\u0142gorzata", "initials": "M"}, {"family": "Das", "given": "Jyotirmoy", "initials": "J"}, {"family": "Malmstr\u00f6m", "given": "Annika", "initials": "A"}, {"family": "S\u00f6derkvist", "given": "Peter", "initials": "P"}], "type": "journal article", "published": "2022-08-25", "journal": {"title": "Front Genet", "issn": "1664-8021", "issn-l": "1664-8021", "volume": "13", "issue": null, "pages": "934519"}, "abstract": "Patients with glioblastoma (GBM) have a poor outcome, but even among patients receiving the same therapies and with good prognostic factors, one can find those with exceptionally short and long survival. From the Nordic trial, which randomized GBM patients of 60 years or older between two radiotherapy arms (60 Gy or 34 Gy) or temozolomide (TMZ), we selected 59 with good prognostic factors. These selected GBM patients were equally distributed according to treatment and MGMT promoter methylation status but had long or short survival. Methylation profiling with the Illumina Infinium Methylation EPIC BeadChip arrays was performed and utilized for methylation-based CNS tumor classification, and pathway enrichment analysis of differentially methylated CpG sites (DMCs), as well as calculation of epigenetic age acceleration with three different algorithms, to compare the long and short survival groups. Samples identified by the classifier as non-GBM IDH wildtype were excluded. DMCs between long- and short-term survivors were found in patients with methylated MGMT promoter treated with TMZ (123,510), those with unmethylated MGMT treated with 60Gy radiotherapy (4,086), and with methylated MGMT promoter treated with 34Gy radiotherapy (39,649). Long-term survivors with methylated MGMT promoter treated with TMZ exhibited hypermethylation of the Wnt signaling and the platelet activation, signaling, and aggregation pathways. The joint analysis of radiotherapy arms revealed 319 DMCs between long- and short-term survivors with unmethylated MGMT and none for samples with methylated MGMT promoter. An analysis comparing epigenetic age acceleration between patients with long- and short-term survival across all treatment arms showed a decreased epigenetic age acceleration for the latter. We identified DMCs for both TMZ and RT-treated patients and epigenetic age acceleration as a potential prognostic marker, but further systematic analysis of larger patient cohorts is necessary for confirmation of their prognostic and/or predictive properties.", "doi": "10.3389/fgene.2022.934519", "pmid": "36092918", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9452748"}, {"db": "pii", "key": "934519"}], "notes": [], "created": "2022-12-01T14:12:23.526Z", "modified": "2024-01-16T13:48:35.090Z"}, {"entity": "publication", "iuid": "d78174c0ff784cde8e1c0db5f6723e3e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d78174c0ff784cde8e1c0db5f6723e3e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d78174c0ff784cde8e1c0db5f6723e3e"}}, "title": "Autosomal recessive congenital hereditary corneal dystrophy associated with a novel SLC4A11 mutation in two consanguineous Tunisian families.", "authors": [{"family": "Chibani", "given": "Zohra", "initials": "Z", "orcid": "0000-0002-5615-1305", "researcher": {"href": "https://publications.scilifelab.se/researcher/a065c32ffbb647d3be825180751f8341.json"}}, {"family": "Abid", "given": "Imen Zone", "initials": "IZ"}, {"family": "S\u00f6derkvist", "given": "Peter", "initials": "P", "orcid": "0000-0001-9867-8706", "researcher": {"href": "https://publications.scilifelab.se/researcher/c1fc163b9a08421180f7f235af3897f4.json"}}, {"family": "Feki", "given": "Jamel", "initials": "J"}, {"family": "Aifa", "given": "Mounira Hmani", "initials": "MH"}], "type": "journal article", "published": "2022-02-00", "journal": {"title": "Br J Ophthalmol", "issn": "1468-2079", "volume": "106", "issue": "2", "pages": "281-287", "issn-l": null}, "abstract": "Autosomal recessive congenital hereditary corneal dystrophy (CHED) is a rare isolated developmental anomaly of the eye characterised by diffuse bilateral corneal clouding that may lead to visual impairment requiring corneal transplantation. CHED is known to be caused by mutations in the solute carrier family 4 member 11 (SLC4A11) gene which encodes a membrane transporter protein (sodium bicarbonate transporter-like solute carrier family 4 member 11).\n\nTo identify SLC4A11 gene mutations associated with CHED (OMIM: #217700), genomic DNA was extracted from whole blood and sequenced for all exons and intron-exon boundaries in two large Tunisian families.\n\nA novel deletion SLC4A11 mutation (p. Leu479del; c.1434_1436del) is responsible for CHED in both analysed families. This non-frameshift mutation was found in a homozygous state in affected members and heterozygous in non-affected members. In silico analysis largely support the pathogenicity of this alteration that may leads to stromal oedema by disrupting the osmolarity balance. Being localised to a region of alpha-helical secondary structure, Leu479 deletion may induce protein-compromising structural rearrangements.\n\nTo the best of our knowledge, this is the first clinical and genetic study exploring CHED in Tunisia. The present work also expands the list of pathogenic genotypes in SLC4A11 gene and its associated clinical diagnosis giving more insights into genotype-phenotype correlations.", "doi": "10.1136/bjophthalmol-2020-318204", "pmid": "33879471", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "bjophthalmol-2020-318204"}], "notes": [], "created": "2022-12-01T14:14:14.879Z", "modified": "2022-12-01T14:14:14.911Z"}, {"entity": "publication", "iuid": "9591fd31f8354bb68ebb9e31259336ef", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9591fd31f8354bb68ebb9e31259336ef.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9591fd31f8354bb68ebb9e31259336ef"}}, "title": "Genetic Alterations in Mitochondrial DNA Are Complementary to Nuclear DNA Mutations in Pheochromocytomas.", "authors": [{"family": "Tabebi", "given": "Mouna", "initials": "M", "orcid": "0000-0002-2873-161X", "researcher": {"href": "https://publications.scilifelab.se/researcher/285705c043f34b55826e7f33ab36a875.json"}}, {"family": "\u0141ysiak", "given": "Ma\u0142gorzata", "initials": "M", "orcid": "0000-0002-0244-759X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a7f5d37e79764c31a5a0a421c34ed1a8.json"}}, {"family": "Dutta", "given": "Ravi Kumar", "initials": "RK"}, {"family": "Lomazzi", "given": "Sandra", "initials": "S"}, {"family": "Turkina", "given": "Maria V", "initials": "MV"}, {"family": "Brunaud", "given": "Laurent", "initials": "L", "orcid": "0000-0001-5182-6660", "researcher": {"href": "https://publications.scilifelab.se/researcher/132c416fbbde4a1f90d4a8c0e95f9f1f.json"}}, {"family": "Gimm", "given": "Oliver", "initials": "O", "orcid": "0000-0002-0054-664X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9879641fb40042ae90ff034f4912a16d.json"}}, {"family": "S\u00f6derkvist", "given": "Peter", "initials": "P"}], "type": "journal article", "published": "2022-01-06", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "volume": "14", "issue": "2", "issn-l": "2072-6694"}, "abstract": "Somatic mutations, copy-number variations, and genome instability of mitochondrial DNA (mtDNA) have been reported in different types of cancers and are suggested to play important roles in cancer development and metastasis. However, there is scarce information about pheochromocytomas and paragangliomas (PCCs/PGLs) formation.\n\nTo determine the potential roles of mtDNA alterations in sporadic PCCs/PGLs, we analyzed a panel of 26 nuclear susceptibility genes and the entire mtDNA sequence of seventy-seven human tumors, using next-generation sequencing, and compared the results with normal adrenal medulla tissues. We also performed an analysis of copy-number alterations, large mtDNA deletion, and gene and protein expression.\n\nOur results revealed that 53.2% of the tumors harbor a mutation in at least one of the targeted susceptibility genes, and 16.9% harbor complementary mitochondrial mutations. More than 50% of the mitochondrial mutations were novel and predicted pathogenic, affecting mitochondrial oxidative phosphorylation. Large deletions were found in 26% of tumors, and depletion of mtDNA occurred in more than 87% of PCCs/PGLs. The reduction of the mitochondrial number was accompanied by a reduced expression of the regulators that promote mitochondrial biogenesis (PCG1\u03b1, NRF1, and TFAM). Further, P62 and LC3a gene expression suggested increased mitophagy, which is linked to mitochondrial dysfunction.\n\nThe pathogenic role of these finding remains to be shown, but we suggest a complementarity and a potential contributing role in PCCs/PGLs tumorigenesis.", "doi": "10.3390/cancers14020269", "pmid": "35053433", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8773562"}, {"db": "pii", "key": "cancers14020269"}], "notes": [], "created": "2022-12-01T14:13:42.523Z", "modified": "2022-12-01T14:13:42.606Z"}, {"entity": "publication", "iuid": "9e917fc376384f4b84269a6daf842b63", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9e917fc376384f4b84269a6daf842b63.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9e917fc376384f4b84269a6daf842b63"}}, "title": "Loss of SDHB Induces a Metabolic Switch in the hPheo1 Cell Line toward Enhanced OXPHOS.", "authors": [{"family": "Tabebi", "given": "Mouna", "initials": "M", "orcid": "0000-0002-2873-161X", "researcher": {"href": "https://publications.scilifelab.se/researcher/285705c043f34b55826e7f33ab36a875.json"}}, {"family": "Kumar Dutta", "given": "Ravi", "initials": "R"}, {"family": "Skoglund", "given": "Camilla", "initials": "C"}, {"family": "S\u00f6derkvist", "given": "Peter", "initials": "P"}, {"family": "Gimm", "given": "Oliver", "initials": "O", "orcid": "0000-0002-0054-664X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9879641fb40042ae90ff034f4912a16d.json"}}], "type": "journal article", "published": "2022-01-05", "journal": {"title": "Int J Mol Sci", "issn": "1422-0067", "volume": "23", "issue": "1", "issn-l": null}, "abstract": "Enzymes of tricarboxylic acid (TCA) have recently been recognized as tumor suppressors. Mutations in the SDHB subunit of succinate dehydrogenase (SDH) cause pheochromocytomas and paragangliomas (PCCs/PGLs) and predispose patients to malignant disease with poor prognosis.\n\nUsing the human pheochromocytoma cell line (hPheo1), we knocked down SDHB gene expression using CRISPR-cas9 technology.\n\nMicroarray gene expression analysis showed that >500 differentially expressed gene targets, about 54%, were upregulated in response to SDHB knock down. Notably, genes involved in glycolysis, hypoxia, cell proliferation, and cell differentiation were up regulated, whereas genes involved in oxidative phosphorylation (OXPHOS) were downregulated. In vitro studies show that hPheo1 proliferation is not affected negatively and the cells that survive by shifting their metabolism to the use of glutamine as an alternative energy source and promote OXPHOS activity. Knock down of SDHB expression results in a significant increase in GLUD1 expression in hPheo1 cells cultured as monolayer or as 3D culture. Analysis of TCGA data confirms the enhancement of GLUD1 in SDHB mutated/low expressed PCCs/PGLs.\n\nOur data suggest that the downregulation of SDHB in PCCs/PGLs results in increased GLUD1 expression and may represent a potential biomarker and therapeutic target in SDHB mutated tumors and SDHB loss of activity-dependent diseases.", "doi": "10.3390/ijms23010560", "pmid": "35008989", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8745660"}, {"db": "pii", "key": "ijms23010560"}], "notes": [], "created": "2022-12-01T14:12:53.382Z", "modified": "2022-12-01T14:12:53.457Z"}, {"entity": "publication", "iuid": "7a1e9b52b85b4900b54de0691a4cdcd4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7a1e9b52b85b4900b54de0691a4cdcd4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7a1e9b52b85b4900b54de0691a4cdcd4"}}, "title": "Increased diagnostic sensitivity of palpation-guided thyroid nodule fine-needle aspiration cytology by BRAF V600E-mutation analysis.", "authors": [{"family": "Gimm", "given": "Oliver", "initials": "O"}, {"family": "Ivansson", "given": "Kristin", "initials": "K"}, {"family": "Beka", "given": "Ervin", "initials": "E"}, {"family": "Rossitti", "given": "Hugo M", "initials": "HM"}, {"family": "Garvin", "given": "Stina", "initials": "S"}, {"family": "S\u00f6derkvist", "given": "Peter", "initials": "P"}], "type": "journal article", "published": "2021-11-00", "journal": {"title": "J Pathol Clin Res", "issn": "2056-4538", "issn-l": null, "volume": "7", "issue": "6", "pages": "556-564"}, "abstract": "Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer and its incidence is increasing. Preoperative diagnosis is warranted in order to avoid 'two-stage' procedures that are associated with additional costs and higher radioactive iodine remnant uptake. In the setting of thyroid cancer, somatic BRAF V600E-mutations are highly specific for PTC and can be analyzed in aspirates from fine-needle aspiration cytology (FNAC). The 'gold standard' to perform FNAC is ultrasound guidance. Here, we analyze whether adding BRAF V600E-mutation analysis could be of value in palpation-guided FNACs. A total of 430 consecutive patients were included. Ultrasound-guided FNACs were performed in 251 patients and 179 patients underwent palpation-guided FNACs. BRAF V600E-mutation analysis was performed using two methods, an allele-specific polymerase chain reaction (PCR) analyzed by capillary gel electrophoresis (PCR/Qiaxcel), and a droplet digital PCR (ddPCR) assay. A total of 80 patients underwent surgery, and histology revealed 25 patients to have PTC. Of the 25 PTCs, 23 (92%) showed a BRAF V600E-mutation. Both mutation analysis methods (PCR/Qiaxcel and ddPCR) produced concordant results. In the ultrasound-guided group, the preoperative diagnostic sensitivity of FNAC using the Bethesda classification alone was very high and additional BRAF V600E-mutation analysis added little to the preoperative diagnostic sensitivity. By contrast, in the palpation-guided group, by adding BRAF V600E-mutation analysis, eight instead of four patients were diagnosed of having PTC. This increase in the diagnostic sensitivity was statistically significant (p < 0.05). The costs per sample were as low as 62 USD (PCR/Qiaxcel and ddPCR) and 35 USD (PCR/Qiaxcel only). Ultrasound-guided FNAC should be aimed for when dealing with thyroid nodules. However, if palpation-guided FNAC cannot be avoided or may be required due to resource utilization, adding BRAF V600E-mutation analysis using the methods described in this study might significantly increase the proportion of preoperatively diagnosed PTCs. The additional costs can be considered very reasonable.", "doi": "10.1002/cjp2.231", "pmid": "34156770", "labels": {"Clinical Genomics Link\u00f6ping": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC8503891"}], "notes": [], "created": "2021-12-09T13:00:37.181Z", "modified": "2021-12-09T13:01:07.696Z"}, {"entity": "publication", "iuid": "b5a78af9634b44bd8bb3760184a70aab", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b5a78af9634b44bd8bb3760184a70aab.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b5a78af9634b44bd8bb3760184a70aab"}}, "title": "5\u00b4XP sRNA-seq: efficient identification of transcripts with and without 5\u00b4 phosphorylation reveals evolutionary conserved small RNA.", "authors": [{"family": "Kugelberg", "given": "Unn", "initials": "U"}, {"family": "N\u00e4tt", "given": "Daniel", "initials": "D", "orcid": "0000-0001-9182-9401", "researcher": {"href": "https://publications.scilifelab.se/researcher/6af95d8800274851babd3c3ecae29c55.json"}}, {"family": "Skog", "given": "Signe", "initials": "S"}, {"family": "Kutter", "given": "Claudia", "initials": "C"}, {"family": "\u00d6st", "given": "Anita", "initials": "A", "orcid": "0000-0003-0547-1904", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7a222183b264e4b828a38c322a4090f.json"}}], "type": "journal article", "published": "2021-11-00", "journal": {"title": "RNA Biol", "issn": "1555-8584", "issn-l": "1547-6286", "volume": "18", "issue": "11", "pages": "1588-1599"}, "abstract": "Small RNA (sRNA) sequencing has been critical for our understanding of many cellular processes, including gene regulation. Nonetheless, the varying biochemical properties of sRNA, such as 5\u00b4 nucleotide modifications, make many sRNA subspecies incompatible with common protocols for sRNA sequencing. Here we describe 5XP-seq that outlines a novel strategy that captures a more complete picture of sRNA. By tagging 5\u00b4P sRNA during library preparation, 5XP-seq combines an open approach that includes all types of 5'-terminal modifications (5\u00b4X), with a selective approach for 5-phosphorylated sRNA (5\u00b4P). We show that 5XP-seq not only enriches phosphorylated miRNA and piRNA but successfully discriminates these sRNA from all other sRNA species. We further demonstrate the importance of this strategy by successful inter-species validation of sRNAs that would have otherwise failed, including human to insect translation of several tRNA (tRFs) and rRNA (rRFs) fragments. By combining 5\u00b4 insensitive library strategies with 5\u00b4 sensitive tagging, we have successfully tackled an intrinsic bias in modern sRNA sequencing that will help us reveal the true complexity and the evolutionary significance of the sRNA world.", "doi": "10.1080/15476286.2020.1861770", "pmid": "33382953", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8594926"}], "notes": [], "created": "2021-12-09T13:05:58.642Z", "modified": "2021-12-09T13:06:07.959Z"}, {"entity": "publication", "iuid": "a6b2471531d94a81a46a5a3d39bc1904", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a6b2471531d94a81a46a5a3d39bc1904.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a6b2471531d94a81a46a5a3d39bc1904"}}, "title": "Genetic Variant Score and Arrhythmogenic Right Ventricular Cardiomyopathy Phenotype in Plakophilin-2 Mutation Carriers.", "authors": [{"family": "Svensson", "given": "Anneli", "initials": "A"}, {"family": "Platonov", "given": "Pyotr G", "initials": "PG"}, {"family": "Haugaa", "given": "Kristina H", "initials": "KH"}, {"family": "Zareba", "given": "Wojciech", "initials": "W"}, {"family": "Jensen", "given": "Henrik Kj\u00e6rulf", "initials": "HK"}, {"family": "Bundgaard", "given": "Henning", "initials": "H"}, {"family": "Gilljam", "given": "Thomas", "initials": "T"}, {"family": "Madsen", "given": "Trine", "initials": "T"}, {"family": "Hansen", "given": "Jim", "initials": "J"}, {"family": "Dejgaard", "given": "Lars A", "initials": "LA"}, {"family": "Karlsson", "given": "Lars O", "initials": "LO"}, {"family": "Gr\u00e9en", "given": "Anna", "initials": "A"}, {"family": "Polonsky", "given": "Bronislava", "initials": "B"}, {"family": "Edvardsen", "given": "Thor", "initials": "T"}, {"family": "Svendsen", "given": "Jesper Hastrup", "initials": "JH"}, {"family": "Gunnarsson", "given": "Cecilia", "initials": "C"}], "type": "journal article", "published": "2021-09-01", "journal": {"title": "Cardiology", "issn": "1421-9751", "issn-l": null, "volume": "146", "issue": "6", "pages": "763-771"}, "abstract": "Whether detailed genetic information contributes to risk stratification of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) remains uncertain. Pathogenic genetic variants in some genes seem to carry a higher risk for arrhythmia and earlier disease onset than others, but comparisons between variants in the same gene have not been done. Combined Annotation Dependent Depletion (CADD) score is a bioinformatics tool that measures the pathogenicity of each genetic variant. We hypothesized that a higher CADD score is associated with arrhythmic events and earlier age at ARVC manifestations in individuals carrying pathogenic or likely pathogenic genetic variants in plakophilin-2 (PKP2).\r\n\r\nCADD scores were calculated using the data from pooled Scandinavian and North American ARVC cohorts, and their association with cardiac events defined as ventricular tachycardia/ventricular fibrillation (VT/VF) or syncope and age at definite ARVC diagnosis were assessed.\r\n\r\nIn total, 33 unique genetic variants were reported in 179 patients (90 males, 71 probands, 96 with definite ARVC diagnosis at a median age of 35 years). Cardiac events were reported in 76 individuals (43%), of whom 53 had sustained VT/VF (35%). The CADD score was neither associated with age at cardiac events (HR 1.002, 95% CI: 0.953-1.054, p = 0.933) nor with age at definite ARVC diagnosis (HR 0.992, 95% CI: 0.947-1.039, p = 0.731).\r\n\r\nNo correlation was found between CADD scores and clinical manifestations of ARVC, indicating that the score has no additional risk stratification value among carriers of pathogenic or likely pathogenic PKP2 genetic variants.", "doi": "10.1159/000519231", "pmid": "34469894", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "000519231"}], "notes": [], "created": "2021-12-09T13:04:21.670Z", "modified": "2021-12-09T13:04:32.527Z"}, {"entity": "publication", "iuid": "7ebf8295ed184e8aacafe62edf908e20", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7ebf8295ed184e8aacafe62edf908e20.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7ebf8295ed184e8aacafe62edf908e20"}}, "title": "EBF1 and PAX5 control pro-B cell expansion via opposing regulation of the Myc gene.", "authors": [{"family": "Somasundaram", "given": "Rajesh", "initials": "R"}, {"family": "Jensen", "given": "Christina T", "initials": "CT", "orcid": "0000-0002-6753-7983", "researcher": {"href": "https://publications.scilifelab.se/researcher/b64daee979c84a59851fdbba4f817060.json"}}, {"family": "Tingvall-Gustafsson", "given": "Johanna", "initials": "J", "orcid": "0000-0002-7359-6584", "researcher": {"href": "https://publications.scilifelab.se/researcher/ad2644c404ce4aa1bfa097dc215b7a39.json"}}, {"family": "\u00c5hsberg", "given": "Josefine", "initials": "J"}, {"family": "Okuyama", "given": "Kazuki", "initials": "K"}, {"family": "Prasad", "given": "Mahadesh", "initials": "M"}, {"family": "Hagman", "given": "James R", "initials": "JR", "orcid": "0000-0002-5436-8455", "researcher": {"href": "https://publications.scilifelab.se/researcher/ee648e9ab5d94f64b92929a7f36761a6.json"}}, {"family": "Wang", "given": "Xun", "initials": "X", "orcid": "0000-0002-1653-5750", "researcher": {"href": "https://publications.scilifelab.se/researcher/70cec474cabe472986bb1ebde2f9e1ab.json"}}, {"family": "Soneji", "given": "Shamit", "initials": "S"}, {"family": "Strid", "given": "Tobias", "initials": "T", "orcid": "0000-0002-2166-5170", "researcher": {"href": "https://publications.scilifelab.se/researcher/8294f89150574803a12bc1944714d12b.json"}}, {"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", "orcid": "0000-0001-8527-7276", "researcher": {"href": "https://publications.scilifelab.se/researcher/b66081f5ee58407b98ed71127aada52d.json"}}], "type": "journal article", "published": "2021-06-03", "journal": {"title": "Blood", "issn": "1528-0020", "issn-l": "0006-4971", "volume": "137", "issue": "22", "pages": "3037-3049"}, "abstract": "Genes encoding B lineage-restricted transcription factors are frequently mutated in B-lymphoid leukemias, suggesting a close link between normal and malignant B-cell development. One of these transcription factors is early B-cell factor 1 (EBF1), a protein of critical importance for lineage specification and survival of B-lymphoid progenitors. Here, we report that impaired EBF1 function in mouse B-cell progenitors results in reduced expression of Myc. Ectopic expression of MYC partially rescued B-cell expansion in the absence of EBF1 both in vivo and in vitro. Using chromosome conformation analysis in combination with ATAC-sequencing, chromatin immunoprecipitation-sequencing, and reporter gene assays, six EBF1-responsive enhancer elements were identified within the Myc locus. CRISPR-Cas9-mediated targeting of EBF1-binding sites identified one element of key importance for Myc expression and pro-B cell expansion. These data provide evidence that Myc is a direct target of EBF1. Furthermore, chromatin immunoprecipitation-sequencing analysis revealed that several regulatory elements in the Myc locus are targets of PAX5. However, ectopic expression of PAX5 in EBF1-deficient cells inhibits the cell cycle and reduces Myc expression, suggesting that EBF1 and PAX5 act in an opposing manner to regulate Myc levels. This hypothesis is further substantiated by the finding that Pax5 inactivation reduces requirements for EBF1 in pro-B-cell expansion. The binding of EBF1 and PAX5 to regulatory elements in the human MYC gene in a B-cell acute lymphoblastic leukemia cell line indicates that the EBF1:PAX5:MYC regulatory loop is conserved and may control both normal and malignant B-cell development.", "doi": "10.1182/blood.2020009564", "pmid": "33619557", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "S0006-4971(21)00417-1"}, {"db": "pmc", "key": "PMC8176764"}], "notes": [], "created": "2021-12-09T13:04:57.591Z", "modified": "2021-12-09T13:05:08.439Z"}, {"entity": "publication", "iuid": "7ad87a3fcb8d447ea1dd7d796d1aa8fe", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7ad87a3fcb8d447ea1dd7d796d1aa8fe.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7ad87a3fcb8d447ea1dd7d796d1aa8fe"}}, "title": "B Lymphocyte Specification Is Preceded by Extensive Epigenetic Priming in Multipotent Progenitors.", "authors": [{"family": "Strid", "given": "Tobias", "initials": "T", "orcid": "0000-0002-2166-5170", "researcher": {"href": "https://publications.scilifelab.se/researcher/8294f89150574803a12bc1944714d12b.json"}}, {"family": "Okuyama", "given": "Kazuki", "initials": "K", "orcid": "0000-0002-0262-9326", "researcher": {"href": "https://publications.scilifelab.se/researcher/23e2f338907b4160938c4ffcbc2c41af.json"}}, {"family": "Tingvall-Gustafsson", "given": "Johanna", "initials": "J", "orcid": "0000-0002-7359-6584", "researcher": {"href": "https://publications.scilifelab.se/researcher/ad2644c404ce4aa1bfa097dc215b7a39.json"}}, {"family": "Kuruvilla", "given": "Jacob", "initials": "J", "orcid": "0000-0002-4034-8752", "researcher": {"href": "https://publications.scilifelab.se/researcher/208b82c92ef34595b82ff206f11a0123.json"}}, {"family": "Jensen", "given": "Christina T", "initials": "CT", "orcid": "0000-0002-6753-7983", "researcher": {"href": "https://publications.scilifelab.se/researcher/b64daee979c84a59851fdbba4f817060.json"}}, {"family": "Lang", "given": "Stefan", "initials": "S", "orcid": "0000-0002-0854-2328", "researcher": {"href": "https://publications.scilifelab.se/researcher/eed2cc9c00a7404d9cd4821a7d0cd92d.json"}}, {"family": "Prasad", "given": "Mahadesh", "initials": "M", "orcid": "0000-0002-5792-6600", "researcher": {"href": "https://publications.scilifelab.se/researcher/1962bcf072cb4f4798063f0a7b43d499.json"}}, {"family": "Somasundaram", "given": "Rajesh", "initials": "R"}, {"family": "\u00c5hsberg", "given": "Josefine", "initials": "J"}, {"family": "Cristobal", "given": "Susana", "initials": "S", "orcid": "0000-0002-3894-2218", "researcher": {"href": "https://publications.scilifelab.se/researcher/b19191785d5145b8b2f37dac311b4d46.json"}}, {"family": "Soneji", "given": "Shamit", "initials": "S"}, {"family": "Ungerb\u00e4ck", "given": "Jonas", "initials": "J"}, {"family": "Sigvardsson", "given": "Mikael", "initials": "M", "orcid": "0000-0001-8527-7276", "researcher": {"href": "https://publications.scilifelab.se/researcher/b66081f5ee58407b98ed71127aada52d.json"}}], "type": "journal article", "published": "2021-06-01", "journal": {"title": "J. Immunol.", "issn": "1550-6606", "issn-l": "0022-1767", "volume": "206", "issue": "11", "pages": "2700-2713"}, "abstract": "B lymphocyte development is dependent on the interplay between the chromatin landscape and lineage-specific transcription factors. It has been suggested that B lineage commitment is associated with major changes in the nuclear chromatin environment, proposing a critical role for lineage-specific transcription factors in the formation of the epigenetic landscape. In this report, we have used chromosome conformation capture in combination with assay for transposase-accessible chromatin sequencing analysis to enable highly efficient annotation of both proximal and distal transcriptional control elements to genes activated in B lineage specification in mice. A large majority of these genes were annotated to at least one regulatory element with an accessible chromatin configuration in multipotent progenitors. Furthermore, the majority of binding sites for the key regulators of B lineage specification, EBF1 and PAX5, occurred in already accessible regions. EBF1 did, however, cause a dynamic change in assay for transposase-accessible chromatin accessibility and was critical for an increase in distal promoter-enhancer interactions. Our data unravel an extensive epigenetic priming at regulatory elements annotated to lineage-restricted genes and provide insight into the interplay between the epigenetic landscape and transcription factors in cell specification.", "doi": "10.4049/jimmunol.2100048", "pmid": "34021049", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "jimmunol.2100048"}], "notes": [], "created": "2021-12-09T13:05:29.934Z", "modified": "2021-12-09T13:05:40.188Z"}, {"entity": "publication", "iuid": "ca9109bdcc344f178c742f6de9c930f9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ca9109bdcc344f178c742f6de9c930f9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ca9109bdcc344f178c742f6de9c930f9"}}, "title": "Complement-Opsonized HIV Modulates Pathways Involved in Infection of Cervical Mucosal Tissues: A Transcriptomic and Proteomic Study.", "authors": [{"family": "Svanberg", "given": "Cecilia", "initials": "C"}, {"family": "Elleg\u00e5rd", "given": "Rada", "initials": "R"}, {"family": "Crisci", "given": "Elisa", "initials": "E"}, {"family": "Khalid", "given": "Mohammad", "initials": "M"}, {"family": "Borendal Wodlin", "given": "Ninnie", "initials": "N"}, {"family": "Svenvik", "given": "Maria", "initials": "M"}, {"family": "Nystr\u00f6m", "given": "Sofia", "initials": "S"}, {"family": "Birse", "given": "Kenzie", "initials": "K"}, {"family": "Burgener", "given": "Adam", "initials": "A"}, {"family": "Shankar", "given": "Esaki M", "initials": "EM"}, {"family": "Larsson", "given": "Marie", "initials": "M"}], "type": "journal article", "published": "2021-05-20", "journal": {"title": "Front Immunol", "issn": "1664-3224", "issn-l": "1664-3224", "volume": "12", "issue": null, "pages": "625649"}, "abstract": "Genital mucosal transmission is the most common route of HIV spread. The initial responses triggered at the site of viral entry are reportedly affected by host factors, especially complement components present at the site, and this will have profound consequences on the outcome and pathogenesis of HIV infection. We studied the initial events associated with host-pathogen interactions by exposing cervical biopsies to free or complement-opsonized HIV. Opsonization resulted in higher rates of HIV acquisition/infection in mucosal tissues and emigrating dendritic cells. Transcriptomic and proteomic data showed a significantly more pathways and higher expression of genes and proteins associated with viral replication and pathways involved in different aspects of viral infection including interferon signaling, cytokine profile and dendritic cell maturation for the opsonized HIV. Moreover, the proteomics data indicate a general suppression by the HIV exposure. This clearly suggests that HIV opsonization alters the initial signaling pathways in the cervical mucosa in a manner that promotes viral establishment and infection. Our findings provide a foundation for further studies of the role these early HIV induced events play in HIV pathogenesis.", "doi": "10.3389/fimmu.2021.625649", "pmid": "34093520", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Bioinformatics Support for Computational Resources": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8173031"}], "notes": [], "created": "2021-12-09T13:03:18.676Z", "modified": "2024-01-16T13:48:39.703Z"}, {"entity": "publication", "iuid": "11b8839fb4694d75bc19aab767987019", "links": {"self": {"href": "https://publications.scilifelab.se/publication/11b8839fb4694d75bc19aab767987019.json"}, "display": {"href": "https://publications.scilifelab.se/publication/11b8839fb4694d75bc19aab767987019"}}, "title": "X-chromosome variants are associated with aldosterone producing adenomas.", "authors": [{"family": "Dutta", "given": "Ravi Kumar", "initials": "RK"}, {"family": "Larsson", "given": "Malin", "initials": "M"}, {"family": "Arnesen", "given": "Thomas", "initials": "T"}, {"family": "Heie", "given": "Anette", "initials": "A"}, {"family": "Walz", "given": "Martin", "initials": "M"}, {"family": "Alesina", "given": "Piero", "initials": "P"}, {"family": "Gimm", "given": "Oliver", "initials": "O"}, {"family": "S\u00f6derkvist", "given": "Peter", "initials": "P"}], "type": "journal article", "published": "2021-05-18", "journal": {"title": "Sci Rep", "issn": "2045-2322", "issn-l": "2045-2322", "volume": "11", "issue": "1", "pages": "10562"}, "abstract": "Aldosterone-producing adenomas (APAs) are a major cause of primary aldosteronism (PA) and are characterized by constitutively producing aldosterone, which leads to hypertension. Several mutations have been identified in ion channels or ion channel-associated genes that result in APAs. To date, no studies have used a genome-wide association study (GWAS) approach to search for predisposing loci for APAs. Thus, we investigated Scandinavian APA cases (n = 35) and Swedish controls (n = 60) in a GWAS and discovered a susceptibility locus on chromosome Xq13.3 (rs2224095, OR = 7.9, 95% CI = 2.8-22.4, P = 1 \u00d7 10-7) in a 4-Mb region that was significantly associated with APA. Direct genotyping of sentinel SNP rs2224095 in a replication cohort of APAs (n = 83) and a control group (n = 740) revealed persistently strong significance (OR = 6.1, 95% CI = 3.5-10.6, p < 0.0005). We sequenced an adjacent gene, MAGEE1, of the sentinel SNP and identified a rare variant in one APA, p.Gly327Glu, which is complementary to other mutations in our primary cohort. Expression quantitative trait loci (eQTL) were investigated on the X-chromosome, and 24 trans-eQTL were identified. Some of the genes identified by trans-eQTL point towards a novel mechanistic explanation for the association of the SNPs with APAs. In conclusion, our study provides further insights into the genetic basis of APAs.", "doi": "10.1038/s41598-021-89986-8", "pmid": "34006971", "labels": {"Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "Clinical Genomics Link\u00f6ping": "Service", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-021-89986-8"}, {"db": "pmc", "key": "PMC8131628"}], "notes": [], "created": "2021-09-16T12:45:50.059Z", "modified": "2024-01-16T13:48:39.732Z"}, {"entity": "publication", "iuid": "30b3109ed04745d48657ef69a51dcdba", "links": {"self": {"href": "https://publications.scilifelab.se/publication/30b3109ed04745d48657ef69a51dcdba.json"}, "display": {"href": "https://publications.scilifelab.se/publication/30b3109ed04745d48657ef69a51dcdba"}}, "title": "Association between inflammasome-related polymorphisms and psoriatic arthritis.", "authors": [{"family": "Juneblad", "given": "K", "initials": "K"}, {"family": "Kastbom", "given": "A", "initials": "A"}, {"family": "Johansson", "given": "L", "initials": "L"}, {"family": "Rantap\u00e4\u00e4-Dahlqvist", "given": "S", "initials": "S"}, {"family": "S\u00f6derkvist", "given": "P", "initials": "P", "orcid": "0000-0001-9867-8706", "researcher": {"href": "https://publications.scilifelab.se/researcher/c1fc163b9a08421180f7f235af3897f4.json"}}, {"family": "Alenius", "given": "G-M", "initials": "G"}], "type": "journal article", "published": "2021-05-00", "journal": {"title": "Scand. J. Rheumatol.", "issn": "1502-7732", "issn-l": "0300-9742", "volume": "50", "issue": "3", "pages": "206-212"}, "abstract": "Objective: Psoriatic arthritis (PsA) is a heterogeneous inflammatory disease associated with psoriasis. Underlying genetic factors are considered important for disease expression and prognosis of PsA. Interleukin-1\u03b2-regulating protein complexes called inflammasomes are associated with several inflammatory diseases, e.g. rheumatoid arthritis and psoriasis. The aim was to determine whether inflammasome-related genetic variation is associated with PsA susceptibility or different disease phenotypes.Method: DNA from 724 patients with PsA and 587 population-based controls from northern Sweden was analysed for single-nucleotide polymorphisms in NLRP3-Q750K (rs35829419), NLRP3 (rs10733113), CARD8-C10X (rs2043211), NLRP1 (rs8079034), and NLRP1 (rs878329).Results: Significant associations were found with the genotype AA (vs AT+TT) of rs2043211 for PsA patients compared with controls [odds ratio (OR), 95% confidence interval (CI) 1.32 (1.05-1.65), p = 0.016]; and between the C-allele of rs878329 and axial involvement of PsA [OR (95% CI) 1.37 (1.02-1.84), p = 0.035], the T-allele of rs8079034 with prescription of conventional synthetic disease-modifying anti-rheumatic drugs [OR (95% CI) 1.76 (1.23-2.53), p = 0.0020], the G-allele of rs10733113 and patients with a skin disease with early onset [OR (95% CI) 1.58 (1.13-2.21), p = 0.007], and the C-allele of rs35829419 and a destructive/deforming disease [OR (95% CI) 1.63 (1.04-2.55), p = 0.030].Conclusions: This study is the first to show an association with a genetic polymorphism in an inflammasome-related gene, CARD8-C10X (rs2043211), in patients with PsA. Associations between different phenotypes of PsA and different polymorphisms of the inflammasome genes were also found. Our results indicate the involvement of inflammasome genes in the pathogenesis and disease expression of PsA.", "doi": "10.1080/03009742.2020.1834611", "pmid": "33300400", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [], "notes": [], "created": "2020-12-11T13:36:44.523Z", "modified": "2021-12-09T12:04:06.558Z"}, {"entity": "publication", "iuid": "d5a79a3f31dc4f9abe7b168539cb06ea", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d5a79a3f31dc4f9abe7b168539cb06ea.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d5a79a3f31dc4f9abe7b168539cb06ea"}}, "title": "Deletions on Chromosome Y and Downregulation of the SRY Gene in Tumor Tissue Are Associated with Worse Survival of Glioblastoma Patients.", "authors": [{"family": "\u0141ysiak", "given": "Ma\u0142gorzata", "initials": "M", "orcid": "0000-0002-0244-759X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a7f5d37e79764c31a5a0a421c34ed1a8.json"}}, {"family": "Smits", "given": "Anja", "initials": "A", "orcid": "0000-0003-4171-2672", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e73b52dac6b4262a1aef442afe4a1f7.json"}}, {"family": "Roodakker", "given": "Kenney Roy", "initials": "KR"}, {"family": "Sandberg", "given": "Elisabeth", "initials": "E", "orcid": "0000-0002-9230-4751", "researcher": {"href": "https://publications.scilifelab.se/researcher/997fb5a248df416d99543a2c7a8e019a.json"}}, {"family": "Dimberg", "given": "Anna", "initials": "A"}, {"family": "Mudaisi", "given": "Munila", "initials": "M"}, {"family": "Bratth\u00e4ll", "given": "Charlotte", "initials": "C"}, {"family": "Strandeus", "given": "Michael", "initials": "M"}, {"family": "Milos", "given": "Peter", "initials": "P"}, {"family": "Hallbeck", "given": "Martin", "initials": "M"}, {"family": "S\u00f6derkvist", "given": "Peter", "initials": "P"}, {"family": "Malmstr\u00f6m", "given": "Annika", "initials": "A", "orcid": "0000-0001-8410-4939", "researcher": {"href": "https://publications.scilifelab.se/researcher/34a15d92ca7442dcaec76288815f724c.json"}}], "type": "journal article", "published": "2021-03-31", "journal": {"title": "Cancers (Basel)", "issn": "2072-6694", "issn-l": "2072-6694", "volume": "13", "issue": "7", "pages": null}, "abstract": "Biological causes of sex disparity seen in the prevalence of cancer, including glioblastoma (GBM), remain poorly understood. One of the considered aspects is the involvement of the sex chromosomes, especially loss of chromosome Y (LOY).\r\n\r\nTumors from 105 isocitrate dehydrogenase (IDH) wild type male GBM patients were tested with droplet digital PCR for copy number changes of ten genes on chromosome Y. Decreased gene expression, a proxy of gene loss, was then analyzed in 225 IDH wild type GBM derived from TCGA and overall survival in both cohorts was tested with Kaplan-Meier log-rank analysis and maximally selected rank statistics for cut-off determination.\r\n\r\nLOY was associated with significantly shorter overall survival (7 vs. 14.6 months, p = 0.0016), and among investigated individual genes survival correlated most prominently with loss of the sex-determining region Y gene (SRY) (10.8 vs. 14.8 months, p = 0.0031). Gene set enrichment analysis revealed that epidermal growth factor receptor, platelet-derived growth factor receptor, and MYC proto-oncogene signaling pathways are associated with low SRY expression.\r\n\r\nOur data show that deletions and reduced gene expression of chromosome Y genes, especially SRY, are associated with reduced survival of male GBM patients and connected to major susceptibility pathways of gliomagenesis.", "doi": "10.3390/cancers13071619", "pmid": "33807423", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "cancers13071619"}, {"db": "pmc", "key": "PMC8036637"}], "notes": [], "created": "2021-12-09T13:01:58.155Z", "modified": "2021-12-09T13:02:14.872Z"}, {"entity": "publication", "iuid": "e3b833e7eec94b1f9efd4308ff203182", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e3b833e7eec94b1f9efd4308ff203182.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e3b833e7eec94b1f9efd4308ff203182"}}, "title": "Sex Disparities in MGMT Promoter Methylation and Survival in Glioblastoma: Further Evidence from Clinical Cohorts.", "authors": [{"family": "Smits", "given": "Anja", "initials": "A", "orcid": "0000-0003-4171-2672", "researcher": {"href": "https://publications.scilifelab.se/researcher/7e73b52dac6b4262a1aef442afe4a1f7.json"}}, {"family": "Lysiak", "given": "Malgorzata", "initials": "M", "orcid": "0000-0002-0244-759X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a7f5d37e79764c31a5a0a421c34ed1a8.json"}}, {"family": "Magnusson", "given": "Andreas", "initials": "A"}, {"family": "Rosell", "given": "Johan", "initials": "J"}, {"family": "S\u00f6derkvist", "given": "Peter", "initials": "P"}, {"family": "Malmstr\u00f6m", "given": "Annika", "initials": "A", "orcid": "0000-0001-8410-4939", "researcher": {"href": "https://publications.scilifelab.se/researcher/34a15d92ca7442dcaec76288815f724c.json"}}], "type": "journal article", "published": "2021-02-03", "journal": {"title": "J Clin Med", "issn": "2077-0383", "issn-l": "2077-0383", "volume": "10", "issue": "4", "pages": null}, "abstract": "Recent studies suggest an overrepresentation of MGMT promoter methylated tumors in females with IDHwt glioblastoma (GBM) compared to males, with a subsequent better response to alkylating treatment.\r\n\r\nTo reveal sex-bound associations that may have gone unnoticed in the original analysis, we re-analyzed two previously published clinical cohorts. One was the multicenter Nordic trial of elderly patients with GBM, randomizing patients into three different treatment arms, including 203 cases with known MGMT promoter methylation status. The other was a population-based study of 179 patients with IDHwt GBM, receiving concomittant radiotherapy and chemotherapy with temozolomide. Cohorts were stratified by sex to test the hypothesis that female sex in combination with MGMT promoter methylation constitutes a subgroup with more favorable outcome.\r\n\r\nThere was a significantly larger proportion of MGMT promoter methylation and better outcome for female patients with MGMT promoter methylated tumors. Results were confirmed in 257 TCGA-derived IDHwt GBM with known sex and MGMT status.\r\n\r\nThese results confirm that patient sex in combination with MGMT promoter methylation is a key determinant in GBM to be considered prior to treatment decisions. Our study also illustrates the need for stratification to identify such sex-bound associations.", "doi": "10.3390/jcm10040556", "pmid": "33546098", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "jcm10040556"}, {"db": "pmc", "key": "PMC7913151"}], "notes": [], "created": "2021-12-09T13:02:39.417Z", "modified": "2021-12-09T13:02:54.428Z"}, {"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": "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": "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": "22c2887206cd4d64832b0acf49b58128", "links": {"self": {"href": "https://publications.scilifelab.se/publication/22c2887206cd4d64832b0acf49b58128.json"}, "display": {"href": "https://publications.scilifelab.se/publication/22c2887206cd4d64832b0acf49b58128"}}, "title": "Novel BEST1 gene mutations associated with two different forms of macular dystrophy in Tunisian families.", "authors": [{"family": "Chibani", "given": "Zohra", "initials": "Z", "orcid": "0000-0002-5615-1305", "researcher": {"href": "https://publications.scilifelab.se/researcher/a065c32ffbb647d3be825180751f8341.json"}}, {"family": "Abid", "given": "Imen Zone", "initials": "IZ"}, {"family": "Molbaek", "given": "Annette", "initials": "A"}, {"family": "S\u00f6derkvist", "given": "Peter", "initials": "P", "orcid": "0000-0001-9867-8706", "researcher": {"href": "https://publications.scilifelab.se/researcher/c1fc163b9a08421180f7f235af3897f4.json"}}, {"family": "Feki", "given": "Jamel", "initials": "J"}, {"family": "Hmani-Aifa", "given": "Mounira", "initials": "M"}], "type": "journal article", "published": "2019-11-00", "journal": {"title": "Clin Exp Ophthalmol", "issn": "1442-9071", "issn-l": null, "volume": "47", "issue": "8", "pages": "1063-1073"}, "abstract": "Epidemiological studies of hereditary eye diseases allowed us to identify two Tunisian families suffering from macular dystrophies: Best vitelliform macular dystrophy (BVMD) and autosomal recessive bestrophinopathy (ARB). The purpose of the current study was to investigate the clinical characteristics and the underlying genetics of these two forms of macular dystrophy.\r\n\r\nComplete ophthalmic examination was performed including optical coherence tomography, electroretinography, electrooculography and autofluoresence imaging in all patients. Genomic DNA was extracted from peripheral blood collected from patients and family members.\r\n\r\nSanger sequencing of all exons of the BEST1 gene in both families identified two new mutations: a missense mutation c.C91A [p.L31 M] at the N-terminal transmembrane domain within the ARB family and a nonsense mutation C1550G (p.S517X) in the C-terminal domain segregating in the BVMD family.\r\n\r\nSeveral mutations of the BEST1 gene have been reported which are responsible for numerous ocular pathologies. To the best of our knowledge, it is the first time we report mutations in this gene in Tunisian families presenting different forms of macular dystrophy. Our report also expands the list of pathogenic BEST1 genotypes and the associated clinical diagnosis.", "doi": "10.1111/ceo.13577", "pmid": "31254423", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [], "notes": [], "created": "2020-12-11T13:39:25.424Z", "modified": "2021-12-09T12:06:18.692Z"}, {"entity": "publication", "iuid": "d66be763c7ba47b3a7863fd83d3c5539", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d66be763c7ba47b3a7863fd83d3c5539.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d66be763c7ba47b3a7863fd83d3c5539"}}, "title": "Assessment of genetic and non-genetic risk factors for venous thromboembolism in glioblastoma - The predictive significance of B blood group.", "authors": [{"family": "Heenkenda", "given": "Menikae K", "initials": "MK"}, {"family": "Malmstr\u00f6m", "given": "Annika", "initials": "A"}, {"family": "Lysiak", "given": "Malgorzata", "initials": "M"}, {"family": "Mudaisi", "given": "Munila", "initials": "M"}, {"family": "Bratth\u00e4ll", "given": "Charlotte", "initials": "C"}, {"family": "Milos", "given": "Peter", "initials": "P"}, {"family": "Strandeus", "given": "Michael", "initials": "M"}, {"family": "\u00c5kesson", "given": "Lisa", "initials": "L"}, {"family": "S\u00f6derkvist", "given": "Peter", "initials": "P", "orcid": "0000-0001-9867-8706", "researcher": {"href": "https://publications.scilifelab.se/researcher/c1fc163b9a08421180f7f235af3897f4.json"}}, {"family": "Uppugunduri", "given": "Srinivas", "initials": "S"}, {"family": "Osman", "given": "Abdimajid", "initials": "A"}], "type": "journal article", "published": "2019-11-00", "journal": {"title": "Thromb. Res.", "issn": "1879-2472", "issn-l": "0049-3848", "volume": "183", "issue": null, "pages": "136-142"}, "abstract": "Venous thromboembolism (VTE) is a common problem among patients with glioblastoma multiforme (GBM) and with some other cancers. Here, we evaluated genetic and non-genetic potential risk factors for VTE among GBM patients.\r\n\r\nA cohort of 139 patients treated with concomitant radiotherapy and temozolomide were included in the study. Next generation sequencing and genotyping approaches were applied to assess genetic risk factors in the haemostatic system. Clinical data including surgery, reoperation as well as blood group and patient information such as age and gender were available from patient records. Logistic regression analysis was performed to asses VTE risk.\r\n\r\nIn the study 47 patients (34%) were diagnosed for VTE during the course of their disease. When genetic and non-genetic potential risk factors were evaluated, only B blood group was found to be significantly associated with VTE incidence (odds ratio [OR] = 6.91; confidence interval [CI] = 2.19-24.14; P = 0.001). In contrast, A and O blood groups did not correlate with VTE risk. Frontal lobe tumor location also seemed to slightly increase VTE risk compared to other brain sites (OR = 3.14; CI = 1.1-10.7) although the significance level was at borderline (P = 0.05). Current study identified B blood group as the component in non-O blood groups that is responsible for increased VTE risk.\r\n\r\nIn conclusion, these results suggest for the first time that B blood group is predictive for VTE incidence among patients with glioblastoma, information that may be potentially valuable when selecting GBM patients who are at risk for VTE for anticoagulant prophylaxis.", "doi": "10.1016/j.thromres.2019.10.009", "pmid": "31677594", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "S0049-3848(19)30454-2"}], "notes": [], "created": "2020-12-11T13:38:23.824Z", "modified": "2021-12-09T12:06:35.265Z"}, {"entity": "publication", "iuid": "eb692bf501da4ac298a328d4a9ab5ed7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/eb692bf501da4ac298a328d4a9ab5ed7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/eb692bf501da4ac298a328d4a9ab5ed7"}}, "title": "A somatic mutation in CLCN2 identified in a sporadic aldosterone-producing adenoma.", "authors": [{"family": "Dutta", "given": "Ravi Kumar", "initials": "RK"}, {"family": "Arnesen", "given": "Thomas", "initials": "T"}, {"family": "Heie", "given": "Anette", "initials": "A"}, {"family": "Walz", "given": "Martin", "initials": "M"}, {"family": "Alesina", "given": "Piero", "initials": "P"}, {"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"}], "type": "case reports", "published": "2019-11-00", "journal": {"title": "Eur. J. Endocrinol.", "issn": "1479-683X", "issn-l": "0804-4643", "volume": "181", "issue": "5", "pages": "K37-K41"}, "abstract": "To screen for CLCN2 mutations in apparently sporadic cases of aldosterone-producing adenomas (APAs).\r\n\r\nRecently, CLCN2, encoding for the voltage-gated chloride channel protein 2 (ClC-2), was identified to be mutated in familial hyperaldosteronism II (FH II). So far, somatic mutations in CLCN2 have not been reported in sporadic cases of APAs. We screened 80 apparently sporadic APAs for mutations in CLCN2. One somatic mutation was identified at p.Gly24Asp in CLCN2. The male patient had a small adenoma in size but high aldosterone levels preoperatively. Postoperatively, the patient had normal aldosterone levels and was clinically cured.\r\n\r\nIn this study, we identified a CLCN2 mutation in a sporadic APA comprising about 1% of all APAs investigated. This mutation was complementary to mutations in other susceptibility genes for sporadic APAs and may thus be a driving mutation in APA formation.", "doi": "10.1530/EJE-19-0377", "pmid": "31491746", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pii", "key": "EJE-19-0377"}], "notes": [], "created": "2020-12-11T13:39:04.440Z", "modified": "2021-12-09T12:06:51.179Z"}, {"entity": "publication", "iuid": "122807c9966645f3ba82349bf707f5eb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/122807c9966645f3ba82349bf707f5eb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/122807c9966645f3ba82349bf707f5eb"}}, "title": "The science of librarianship. University of Wales at Aberystwyth, July 31, 1917.", "authors": [{"family": "Osler", "given": "William", "initials": "W"}], "type": "biography", "published": "2012-10-00", "journal": {"title": "J Med Libr Assoc", "issn": "1558-9439", "volume": "100", "issue": "4 Suppl", "pages": "A", "issn-l": null}, "abstract": null, "doi": null, "pmid": "23509423", "labels": {"Clinical Genomics Link\u00f6ping": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC3571674"}, {"db": "sici", "key": "i1536-5050-100-4s-70"}], "notes": [], "created": "2024-12-10T08:20:39.447Z", "modified": "2024-12-10T08:20:39.454Z"}]}