{"entity": "label", "iuid": "5c46c066293f4bd9866ddcde0267fd16", "timestamp": "2026-08-14T19:08:10.746Z", "links": {"self": {"href": "https://publications.scilifelab.se/label/Integrated%20Microscopy%20Technologies%20Gothenburg.json"}, "display": {"href": "https://publications.scilifelab.se/label/Integrated%20Microscopy%20Technologies%20Gothenburg"}}, "value": "Integrated Microscopy Technologies Gothenburg", "started": "2021", "ended": null, "created": "2020-01-20T13:29:57.964Z", "modified": "2021-05-24T15:37:29.085Z", "accounts": [{"entity": "account", "iuid": "32a436398938412b93e7ddcef018c708", "timestamp": "2026-08-14T19:08:10.746Z", "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": "3a621f530b1f416eb5682efbeba080fd", "timestamp": "2026-08-14T19:08:10.746Z", "links": {"self": {"href": "https://publications.scilifelab.se/account/julia.fernandez-rodriguez%40cci.sahlgrenska.gu.se.json"}, "display": {"href": "https://publications.scilifelab.se/account/julia.fernandez-rodriguez%40cci.sahlgrenska.gu.se"}}, "email": "julia.fernandez-rodriguez@cci.sahlgrenska.gu.se", "name": "Julia Fernandez-Rodriguez", "orcid": null, "role": "curator", "status": "enabled", "login": "2024-11-15T11:57:36.356Z", "created": "2020-01-23T15:45:40.093Z", "modified": "2024-11-15T11:57:36.356Z"}, {"entity": "account", "iuid": "5975648a6cc54cab99663a7f8b57059d", "timestamp": "2026-08-14T19:08:10.746Z", "links": {"self": {"href": "https://publications.scilifelab.se/account/rafael.camacho%40gu.se.json"}, "display": {"href": "https://publications.scilifelab.se/account/rafael.camacho%40gu.se"}}, "email": "rafael.camacho@gu.se", "name": "Rafael Camacho", "orcid": "0000-0003-2325-6407", "role": "curator", "status": "enabled", "login": "2026-08-11T10:28:08.004Z", "created": "2025-11-05T11:12:50.019Z", "modified": "2026-08-11T10:28:08.004Z"}, {"entity": "account", "iuid": "6a38350bd21f4fb6aeeb1530037a99ae", "timestamp": "2026-08-14T19:08:10.746Z", "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": "f181766986764ac9bf4af678853bf084", "timestamp": "2026-08-14T19:08:10.746Z", "links": {"self": {"href": "https://publications.scilifelab.se/account/nhu.phan%40chem.gu.se.json"}, "display": {"href": "https://publications.scilifelab.se/account/nhu.phan%40chem.gu.se"}}, "email": "nhu.phan@chem.gu.se", "name": "Thi Ngoc Nhu Phan", "orcid": "0000-0002-3576-0494", "role": "curator", "status": "enabled", "login": "2026-03-09T13:33:45.777Z", "created": "2025-10-20T17:25:50.634Z", "modified": "2026-03-10T15:00:31.085Z"}], "publications_count": 288, "publications": [{"entity": "publication", "iuid": "b78f3eeef25f4e599011e3b7579d85b3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b78f3eeef25f4e599011e3b7579d85b3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b78f3eeef25f4e599011e3b7579d85b3"}}, "title": "The mouse gastric surface epithelial cell and its response to early Helicobacter pylori infection.", "authors": [{"family": "Erhardsson", "given": "Mattias", "initials": "M", "orcid": "0000-0002-5631-2033", "researcher": {"href": "https://publications.scilifelab.se/researcher/fc48a126473e4b2aa69c704186c52466.json"}}, {"family": "Santos", "given": "Lic\u00ednia", "initials": "L", "orcid": "0000-0003-0056-4490", "researcher": {"href": "https://publications.scilifelab.se/researcher/45bac37404464b80b9307e04d9637422.json"}}, {"family": "Benktander", "given": "John", "initials": "J", "orcid": "0009-0009-8464-1211", "researcher": {"href": "https://publications.scilifelab.se/researcher/610344560242423e95a85316b6524fd2.json"}}, {"family": "Sharba", "given": "Sinan", "initials": "S", "orcid": "0000-0003-0531-2137", "researcher": {"href": "https://publications.scilifelab.se/researcher/81071cdd1eeb417797940fa3b8f43590.json"}}, {"family": "Thorell", "given": "Kaisa", "initials": "K", "orcid": "0000-0002-4447-8968", "researcher": {"href": "https://publications.scilifelab.se/researcher/badb913f91e14489aca247ee841e1608.json"}}, {"family": "Lind\u00e9n", "given": "Sara", "initials": "S", "orcid": "0000-0002-7751-9586", "researcher": {"href": "https://publications.scilifelab.se/researcher/9cc996ac3e85427a96dfab4f757ba3b8.json"}}], "type": "journal article", "published": "2026-12-00", "journal": {"title": "Virulence", "issn": "2150-5608", "volume": "17", "issue": "1", "pages": "2645859", "issn-l": "2150-5594"}, "abstract": "Helicobacter pylori infection is the main risk factor for gastric cancer. H. pylori easily develop antibiotic resistance and evade host defenses. In-depth knowledge of the first barrier that H. pylori encounter, the gastric surface mucus-producing epithelial cells (SMCs), may enable improved treatment and prevention. This study aimed to characterize SMC gene expression, mucus glycosylation, and identify how H. pylori colonization affects these parameters. The glycosylation of eight H. pylori-infected and eight sham control mice was characterized by mass spectrometry. SMCs from five infected and five sham control mice were extracted with laser microdissection (LCM) and sequenced with RNA sequencing (RNA-Seq). SMCs were characterized by high gene expression for proteins secreted into mucus (Tff1, Gkn1, Gkn2, Psca, and Muc5ac), mitoribosome RNA, and cytoskeleton proteins. Mucin glycans were large, complex, heavily fucosylated, and dense with H-antigen motifs. Two main glycosylation pathways ending in H-antigen glycans were identified and corroborated with glycosyltransferase expression. Glycosylation was consistent between H. pylori-infected and sham control mice. RNA-Seq data was analysed for differential gene expression, gene set enrichment analysis, and network analysis of functionally-related genes. The analyses revealed that genes required for protein synthesis and oxidative phosphorylation were down-regulated in infected mice. Most up-regulated genes were either interferon-stimulated genes or able to induce interferon production themselves. Depletion of Nkx6-3 occurred in the infected mice, indicating initiation of a pre-cancerous cascade. LCM RNA-Seq of SMCs was thus feasible and enabled characterization of the SMC and definition of a gene set showing how H. pylori infection affects SMCs.", "doi": "10.1080/21505594.2026.2645859", "pmid": "41824631", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC13020875"}], "notes": [], "created": "2026-08-11T10:33:02.075Z", "modified": "2026-08-11T10:33:03.353Z"}, {"entity": "publication", "iuid": "44993dc1b1d84113a5b844e487253e4d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/44993dc1b1d84113a5b844e487253e4d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/44993dc1b1d84113a5b844e487253e4d"}}, "title": "A pcyt-1 allelic series reveals in vivo consequences of reduced phosphatidylcholine synthesis in C. elegans.", "authors": [{"family": "Qvist", "given": "August", "initials": "A"}, {"family": "Kaper", "given": "Delaney", "initials": "D", "orcid": "0000-0002-9929-8104", "researcher": {"href": "https://publications.scilifelab.se/researcher/e96d29226c884ec496240844de56499a.json"}}, {"family": "Henricsson", "given": "Marcus", "initials": "M", "orcid": "0000-0002-4202-0339", "researcher": {"href": "https://publications.scilifelab.se/researcher/01a323cbf0a24269bd32bfc34539e021.json"}}, {"family": "Stjernman", "given": "Albin", "initials": "A"}, {"family": "Bor\u00e9n", "given": "Jan", "initials": "J"}, {"family": "Pilon", "given": "Marc", "initials": "M", "orcid": "0000-0003-3919-2882", "researcher": {"href": "https://publications.scilifelab.se/researcher/d45c4ecf9afe463c971af2de53a770a8.json"}}], "type": "journal article", "published": "2026-08-05", "journal": {"title": "G3 (Bethesda)", "issn": "2160-1836", "volume": "16", "issue": "8", "issn-l": "2160-1836"}, "abstract": "Phosphatidylcholine (PC) is the most abundant phospholipid in eukaryotic membranes and is synthesized in part via the rate-limiting enzyme PCYT1A. In humans, hypomorphic PCYT1A variants cause diverse disorders. To define how graded reductions in PC synthesis affect organismal physiology, we generated and characterized a series of mutant alleles in the Caenorhabditis elegans homolog pcyt-1, including variants corresponding to disease-causing human mutations, as well as an auxin-inducible degradation allele. We identify a clear allelic hierarchy. The V146M variant is embryonic lethal, whereas A97T is largely benign. P154A is temperature-sensitive, and C211Y causes growth delay, reduced brood size, sterility, and lengthened lifespan at standard temperature. Phenotypes of C211Y are rescued by choline, CDP-choline, or PC supplementation, supporting reduced enzymatic function. Lipidomic profiling reveals that decreased PC synthesis consistently increases long-chain polyunsaturated fatty acids (LCPUFAs) in both PCs and phosphatidylethanolamine (PEs) at the expense of shorter saturated species, without markedly altering the PC/PE ratio at 20 \u00b0C. At elevated temperature, the P154A variant exhibits protein instability and a decreased PC/PE ratio. Despite significant lipid remodeling, canonical ER, mitochondrial, and metabolic stress GFP-based reporters are not activated; only the oxidative stress response is elevated, consistent with increased peroxidation-prone LCPUFAs in the pcyt-1 mutant. Acute auxin-induced degradation of PCYT-1 in larvae causes developmental arrest, while acute PCYT-1 degradation in adults disrupts oogenesis, demonstrating a continuous requirement for PC synthesis. Together, these findings establish a functional pcyt-1 allelic series and show that limiting PC synthesis drives compensatory remodeling toward LCPUFA-enriched membranes while rendering the germline particularly vulnerable.", "doi": "10.1093/g3journal/jkag161", "pmid": "42400359", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC13439949"}, {"db": "pii", "key": "8724733"}], "notes": [], "created": "2026-08-11T10:58:28.374Z", "modified": "2026-08-11T10:58:28.439Z"}, {"entity": "publication", "iuid": "04f55e0fd8d34e0395a7592c12fe34e5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/04f55e0fd8d34e0395a7592c12fe34e5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/04f55e0fd8d34e0395a7592c12fe34e5"}}, "title": "Bacterial membrane vesicles as effective immunotherapeutic agents in melanoma, colon, and breast cancer", "authors": [{"family": "L\u00f6tvall", "given": "Jan", "initials": "J"}, {"family": "Ordouzadeh", "given": "Negar", "initials": "N"}, {"family": "Park", "given": "Kyong Su", "initials": "KS", "orcid": "0000-0003-0902-7800", "researcher": {"href": "https://publications.scilifelab.se/researcher/26e308b29fe144b49f4db27f4b819c18.json"}}], "type": "journal-article", "published": "2026-07-06", "journal": {"title": "Extracell Vesicles Circ Nucleic Acids.", "issn": "2767-6641", "volume": "7", "issue": "3", "pages": "1043-55", "issn-l": null}, "abstract": null, "doi": "10.20517/evcna.2026.07", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2026-08-11T10:51:36.433Z", "modified": "2026-08-11T10:51:36.553Z"}, {"entity": "publication", "iuid": "caef8125510744f9b73edc95dffe9be7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/caef8125510744f9b73edc95dffe9be7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/caef8125510744f9b73edc95dffe9be7"}}, "title": "Live bacteria nitrogen uptake in response to winter warming in dry Arctic heath", "authors": [{"family": "R\u00fctting", "given": "Louise", "initials": "L", "orcid": "0000-0002-4890-889X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a935b459f82b4964b59fb61b38daf5c5.json"}}, {"family": "Rodas", "given": "Sofia", "initials": "S"}, {"family": "Rasmussen", "given": "Laura", "initials": "L"}, {"family": "Ranjbari", "given": "Elias", "initials": "E"}, {"family": "Micaroni", "given": "Massimo", "initials": "M"}, {"family": "Elberling", "given": "Bo", "initials": "B"}, {"family": "Danielsen", "given": "Birgitte", "initials": "B"}, {"family": "Patchett", "given": "Aurora", "initials": "A"}, {"family": "R\u00fctting", "given": "Tobias", "initials": "T"}, {"family": "Bj\u00f6rkman", "given": "Mats", "initials": "M", "orcid": "0000-0001-5768-1976", "researcher": {"href": "https://publications.scilifelab.se/researcher/9821ee4a87c74dde82d9a6a4ebc2b1fc.json"}}, {"family": "Zou", "given": "Hanbang", "initials": "H"}, {"family": "Arellano-Caicedo", "given": "Carlos", "initials": "C"}, {"family": "Hammer", "given": "Edith", "initials": "E"}], "type": "posted-content", "published": "2026-06-18", "journal": {"issn-l": null}, "abstract": null, "doi": "10.22541/authorea.15004908/v1", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Technology development"}, "xrefs": [], "notes": [], "created": "2026-08-11T10:59:44.203Z", "modified": "2026-08-11T10:59:44.251Z"}, {"entity": "publication", "iuid": "93517b21a85347649ea42ff641c2de91", "links": {"self": {"href": "https://publications.scilifelab.se/publication/93517b21a85347649ea42ff641c2de91.json"}, "display": {"href": "https://publications.scilifelab.se/publication/93517b21a85347649ea42ff641c2de91"}}, "title": "Correlating Molecule Counts with Stress Granule Size Using Novel Platinized Carbon Nanopore Electrodes.", "authors": [{"family": "Wang", "given": "Yue", "initials": "Y"}, {"family": "Gu", "given": "Chaoyi", "initials": "C"}, {"family": "Gu", "given": "Hui", "initials": "H", "orcid": "0000-0002-2964-3531", "researcher": {"href": "https://publications.scilifelab.se/researcher/9ac443460e0645178c998807ce3ec8d9.json"}}, {"family": "Zhao", "given": "Yingjie", "initials": "Y"}, {"family": "Wang", "given": "Dengchao", "initials": "D", "orcid": "0000-0002-4909-7830", "researcher": {"href": "https://publications.scilifelab.se/researcher/2486819e9f1640f4aa7602d5c6cc5ad9.json"}}, {"family": "Ewing", "given": "Andrew G", "initials": "AG", "orcid": "0000-0002-2084-0133", "researcher": {"href": "https://publications.scilifelab.se/researcher/c6ecb82dc7a6423fa0876822f5568e1b.json"}}], "type": "journal article", "published": "2026-06-16", "journal": {"title": "Anal. Chem.", "issn": "1520-6882", "volume": "98", "issue": "23", "pages": "17153-17160", "issn-l": "0003-2700"}, "abstract": "Stress granules (SGs) are membraneless dynamic structures formed through liquid-liquid phase separation (LLPS) under stress conditions; they can pause nonessential translation and reprogram gene expression to cope with stress, thus being crucial for cell survival. This study pioneers an oxidative stress model that links SG size to redox regulation. Novel platinized carbon nanotube nanopipettes (Pt-CNTNPs) were employed for SG impact electrochemical cytometry (SGIEC) and intracellular SGIEC (ISGIEC) measurements, correlating H2O2 content with SG dimensions through a size-exclusion mechanism. Gaussian fitting quantified the distribution of H2O2 molecule number, and data from PEG8000 solutions demonstrated that intracellular-extracellular content number disparities are likely attributable to macromolecular crowding. All of the results confirm that H2O2 generation in SGs is governed by an interfacial electric field. By establishing a quantitative SG-mediated redox framework, this study provides novel insights into LLPS and opens avenues for targeted therapies and biomimetic materials.", "doi": "10.1021/acs.analchem.6c01191", "pmid": "42227104", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC13276837"}], "notes": [], "created": "2026-08-11T11:00:21.007Z", "modified": "2026-08-11T11:00:21.119Z"}, {"entity": "publication", "iuid": "dfea1f73638f41a2ad82bbfdf3ef86fe", "links": {"self": {"href": "https://publications.scilifelab.se/publication/dfea1f73638f41a2ad82bbfdf3ef86fe.json"}, "display": {"href": "https://publications.scilifelab.se/publication/dfea1f73638f41a2ad82bbfdf3ef86fe"}}, "title": "Frozen melanoma tissues yield extracellular vesicles with preserved diagnostic and immunogenic properties.", "authors": [{"family": "D Arrigo", "given": "Daniele", "initials": "D"}, {"family": "Park", "given": "Kyong-Su", "initials": "KS"}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C"}, {"family": "Sigalas", "given": "Georgios Panagiotis", "initials": "GP"}, {"family": "Symonds", "given": "Emma", "initials": "E"}, {"family": "Urz\u00ed", "given": "Ornella", "initials": "O"}, {"family": "Locatelli", "given": "Camilla", "initials": "C"}, {"family": "Olofsson Bagge", "given": "Roger", "initials": "R"}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J"}, {"family": "Crescitelli", "given": "Rossella", "initials": "R"}], "type": "journal article", "published": "2026-05-21", "journal": {"title": "BMC Med", "issn": "1741-7015", "volume": "24", "issue": "1", "issn-l": "1741-7015"}, "abstract": "Extracellular vesicles (EVs) isolated from tumor tissues carry disease-associated proteins and surface antigens, making them promising candidates for cancer diagnostics and immunotherapy. For EV-based approaches to reach clinical application, it is essential that functional EVs can be obtained from clinically accessible materials, including cryopreserved tumor tissues stored in biobanks. Whether cryopreservation alters EV integrity and function remains unclear. This study evaluates whether EVs derived from cryopreserved tumor tissues retain key molecular and biological properties required for diagnostic and therapeutic use.\n\nEVs were isolated from human metastatic melanoma tissues processed immediately after surgical resection (fresh) or after storage at - 80 \u00b0C (frozen), using a protocol consistent with standard biobank procedures. EV isolation was performed through ultracentrifugation followed by an iodixanol density cushion. The resulting EVs were characterized by transmission electron microscopy, nanoparticle tracking analysis, and mass spectrometry to assess EV morphology, purity, and molecular composition. The diagnostic potential was evaluated by examining the presence of previously identified cancer-associated membrane proteins. Furthermore, therapeutic potential was assessed in vivo by co-administering EVs from fresh or frozen melanoma tissues with synthetic bacterial vesicles and evaluating their effects on tumor growth in melanoma-bearing mice.\n\nEVs from fresh and frozen tissues showed similar morphology, size distribution, yield, and purity. Moreover, the protein composition, including cancer-associated markers such as MT-CO2, COX6c, SLC24A22, HLA-DR, and Erlin2, was highly consistent between EVs derived from fresh and frozen tissues, with no relevant enrichment of intracellular or mitochondrial contaminants in frozen-derived EVs. Functionally, EVs from cryopreserved tissues combined with synthetic bacterial vesicles significantly inhibited tumor progression in vivo, demonstrating antitumor effects comparable to those of EVs from fresh tissues.\n\nOur results validate cryopreserved tissues as a reliable source of functional EVs, comparable to fresh tissues. This supports the potential use of existing biobanks for retrospective EV-based biomarker discovery and functional research.", "doi": "10.1186/s12916-026-04923-8", "pmid": "42169004", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC13198046"}, {"db": "pii", "key": "10.1186/s12916-026-04923-8"}], "notes": [], "created": "2026-08-11T10:49:46.245Z", "modified": "2026-08-11T10:49:46.268Z"}, {"entity": "publication", "iuid": "5fda29738457420fa39479ed5f00fe64", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5fda29738457420fa39479ed5f00fe64.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5fda29738457420fa39479ed5f00fe64"}}, "title": "Dysregulation of glycogen metabolism in cardiomyopathy caused by glycogenin-1 (GYG1) missense variants.", "authors": [{"family": "Visuttijai", "given": "Kittichate", "initials": "K", "orcid": "0000-0002-4800-8533", "researcher": {"href": "https://publications.scilifelab.se/researcher/f41f59ad2b0a4e1c95b0cc9cf109f6fa.json"}}, {"family": "Hedberg-Oldfors", "given": "Carola", "initials": "C", "orcid": "0000-0002-7141-4185", "researcher": {"href": "https://publications.scilifelab.se/researcher/dc67028bf0c04f1b9a73bac5e72f9897.json"}}, {"family": "Braun", "given": "Oscar", "initials": "O", "orcid": "0000-0003-3263-2718", "researcher": {"href": "https://publications.scilifelab.se/researcher/84a44ea29d9e44cdb2894f0ff8bbd7c8.json"}}, {"family": "Englund", "given": "Elisabet", "initials": "E", "orcid": "0000-0002-2708-2443", "researcher": {"href": "https://publications.scilifelab.se/researcher/8c98fa2b2e7e4e318cd00eb1e8e3ac7a.json"}}, {"family": "Glamuzina", "given": "Emma", "initials": "E", "orcid": "0009-0003-4452-8579", "researcher": {"href": "https://publications.scilifelab.se/researcher/040254d5ae4242269523da3425f5074a.json"}}, {"family": "Turner", "given": "Clinton", "initials": "C", "orcid": "0000-0002-2138-7633", "researcher": {"href": "https://publications.scilifelab.se/researcher/a23d726969754ebda4247de99f8360b0.json"}}, {"family": "Vukusic", "given": "Kristina", "initials": "K", "orcid": "0000-0002-4243-0565", "researcher": {"href": "https://publications.scilifelab.se/researcher/342e325123674e74963ae7c4dd307874.json"}}, {"family": "Sandstedt", "given": "Joakim", "initials": "J", "orcid": "0000-0002-6458-9550", "researcher": {"href": "https://publications.scilifelab.se/researcher/070e186990424c4b83225eb93efc2a66.json"}}, {"family": "Dellgren", "given": "G\u00f6ran", "initials": "G", "orcid": "0000-0003-4961-9704", "researcher": {"href": "https://publications.scilifelab.se/researcher/2d5ee559ab58458197bab1d119a50824.json"}}, {"family": "Karason", "given": "Kristjan", "initials": "K", "orcid": "0000-0002-2802-1191", "researcher": {"href": "https://publications.scilifelab.se/researcher/c0fb0087cd3f4779a34eb5475c83c1f9.json"}}, {"family": "Oldfors", "given": "Anders", "initials": "A", "orcid": "0000-0003-2523-1414", "researcher": {"href": "https://publications.scilifelab.se/researcher/864bc00c4e234e2aa204e697a9b1d434.json"}}], "type": "journal article", "published": "2026-05-21", "journal": {"title": "J. Clin. Endocrinol. Metab.", "issn": "1945-7197", "issn-l": "0021-972X"}, "abstract": "Glycogen storage diseases are inherited disorders of glycogen metabolism and are commonly associated with hypoglycaemia, hepatic dysfunction, or skeletal and cardiac myopathy, depending on the affected enzyme. Glycogen storage disease type 15 (GSD15) is caused by pathogenic variants in GYG1, which encodes glycogenin-1, the auto-glucosylating primer required for glycogen synthesis. GSD15 is characterized by cardiomyopathy and storage of abnormal glycogen and polyglucosan in cardiomyocytes.\n\nTo understand the pathobiology of GSD15, we investigated the storage material in heart explants from two previously reported patients and describe a new case of GSD15.\n\nThe characteristic storage material was investigated using laser capture microdissection followed by quantitative mass spectrometry (MS) and immunohistochemistry comparing differentially abundant proteins in the storage material with normal-appearing cytoplasmic regions from the same patient. Global protein dysregulation in GSD15 was assessed by quantitative MS of whole-myocardial tissue samples from patients and normal controls.\n\nThe storage material was enriched in proteins involved in glycogen metabolism, including glycogen synthase, UDP-glucose pyrophosphorylase 2, glycogenin-1, glycogen phosphorylase, and glycogen debranching enzyme. Sequestosome 1 (p62) and desmin were also enriched, without evidence of increased autophagocytosis. Whole-tissue analyses revealed upregulation of cardiomyopathy-associated biomarkers and downregulation of mitochondrial proteins, suggesting impaired energy metabolism contributing. to congestive heart failure.\n\nIn GSD15, storage of abnormal glycogen in cardiomyocytes is associated with enrichment of specific proteins involved in glycogen metabolism, contributing to dysregulation of glycogen turnover. This dysregulation results in polyglucosan accumulation, disruption of sarcomeric and mitochondrial architecture, and progressive fibrosis. No disease-modifying therapy currently exists for GSD15; future strategies based on substrate reduction, enhancement of autophagy, or gene therapy require further investigation.", "doi": "10.1210/clinem/dgag212", "pmid": "42165248", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "8688847"}], "notes": [], "created": "2026-08-11T11:00:18.664Z", "modified": "2026-08-11T11:00:18.977Z"}, {"entity": "publication", "iuid": "98ad877f930a498fa5bc1eda20b40014", "links": {"self": {"href": "https://publications.scilifelab.se/publication/98ad877f930a498fa5bc1eda20b40014.json"}, "display": {"href": "https://publications.scilifelab.se/publication/98ad877f930a498fa5bc1eda20b40014"}}, "title": "Comparative biodegradation of functionalized graphene oxide nanosheets by myeloperoxidase and neutrophil extracellular traps.", "authors": [{"family": "Bahmani", "given": "Mohsen", "initials": "M"}, {"family": "Gholami", "given": "Asma", "initials": "A"}, {"family": "Ghaeidamini", "given": "Marziyeh", "initials": "M"}, {"family": "Cao", "given": "Zhejian", "initials": "Z"}, {"family": "Gharib-Zahedi", "given": "Mohammad Reza", "initials": "MR"}, {"family": "Sanpui", "given": "Pallab", "initials": "P"}, {"family": "Esbj\u00f6rner", "given": "Elin K", "initials": "EK"}, {"family": "Eriksson", "given": "Leif A", "initials": "LA"}, {"family": "Mijakovic", "given": "Ivan", "initials": "I"}, {"family": "Rahimi", "given": "Shadi", "initials": "S"}], "type": "journal article", "published": "2026-05-13", "journal": {"title": "Front Bioeng Biotechnol", "issn": "2296-4185", "volume": "14", "pages": "1797692", "issn-l": null}, "abstract": "Graphene oxide (GO) nanosheets have attracted significant interest as potential carriers for drug delivery due to their unique physicochemical properties and large surface area. However, concerns regarding their cytotoxicity and biodegradability must be addressed before clinical translation. In this study, we aimed to evaluate the biocompatibility and biodegradation of GO functionalized with polyethylene glycol (PEG) and polyethyleneimine (PEI), two commonly used polymers in biomedical applications.\n\nThe interactions of GO, GO-PEG, and GO-PEI with granulocyte-like cells were investigated to determine their effects on cell viability and their susceptibility to immune-mediated degradation. Biodegradation of the materials was assessed using Raman spectroscopy after exposure to granulocyte-like cells, neutrophil extracellular traps (NETs), and myeloperoxidase (MPO), a key enzyme present in NETs. In addition, circular dichroism (CD) spectroscopy was used to evaluate structural changes in MPO upon interaction with the materials, and molecular dynamics simulations were performed to investigate the interaction of hypochlorous acid (HOCl), the catalytic product of MPO, with GO and its functionalized derivatives.\n\nThe results showed that functionalization with PEG or PEI significantly improved cell viability compared with pristine GO. Although GO was structurally modified by granulocyte-like cells, NETs, and MPO, GO-PEG did not show significant degradation under these conditions. In contrast, GO-PEI was susceptible to structural modification by both NETs and MPO. CD analysis indicated that MPO maintained a more stable secondary structure in the presence of GO-PEI compared with GO or GO-PEG under oxidative conditions, suggesting that MPO-generated HOCl may play a key role in GO-PEI degradation. Molecular dynamics simulations further demonstrated stronger interaction and retention of HOCl in GO-PEG and GO-PEI systems compared with pristine GO, indicating an enhanced interaction between oxidants and the functionalized materials. Overall, these findings demonstrate that polymer functionalization significantly influences the biocompatibility and immune-mediated structural modification of GO. Importantly, this study provides new mechanistic insights into how PEG and PEI modifications affect MPO-driven oxidative degradation pathways of graphene oxide-based nanomaterials. These results highlight GO-PEI as a biodegradable and biocompatible candidate for future biomedical and drug delivery applications.", "doi": "10.3389/fbioe.2026.1797692", "pmid": "42212168", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC13213391"}, {"db": "pii", "key": "1797692"}], "notes": [], "created": "2026-08-11T10:49:41.032Z", "modified": "2026-08-11T10:49:41.061Z"}, {"entity": "publication", "iuid": "f6441cef6784418381757591b1503c0c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f6441cef6784418381757591b1503c0c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f6441cef6784418381757591b1503c0c"}}, "title": "Extracellular Vesicle-Enriched Secretome from Mesenchymal Stromal Cells Protects Against Chemically, Particulate-, and Ischemia-Induced Innate-Immunity Induced Inflammation", "authors": [{"family": "Park", "given": "Kyong Su", "initials": "KS", "orcid": "0000-0003-0902-7800", "researcher": {"href": "https://publications.scilifelab.se/researcher/26e308b29fe144b49f4db27f4b819c18.json"}}, {"family": "Ordouzadeh", "given": "Negar", "initials": "N"}, {"family": "Lazzari", "given": "Lorenza", "initials": "L", "orcid": "0000-0002-9434-4538", "researcher": {"href": "https://publications.scilifelab.se/researcher/fb183e5fda7e410bb65bdcf71a6249f6.json"}}, {"family": "Elia", "given": "Noemi", "initials": "N"}, {"family": "Scarpitta", "given": "Serena", "initials": "S", "orcid": "0009-0009-0394-5089", "researcher": {"href": "https://publications.scilifelab.se/researcher/0325c3ce26424d509efcf43272bc5b38.json"}}, {"family": "Iachini", "given": "Maria Chiara", "initials": "MC", "orcid": "0000-0001-8724-8532", "researcher": {"href": "https://publications.scilifelab.se/researcher/42db90ca136f48f6b7fc917ec478d3bf.json"}}, {"family": "Bussolati", "given": "Benedetta", "initials": "B", "orcid": "0000-0002-3663-5134", "researcher": {"href": "https://publications.scilifelab.se/researcher/543f4a1c4f8440dabd5c53646bf23080.json"}}, {"family": "Bruno", "given": "Stefania", "initials": "S", "orcid": "0000-0002-8879-9536", "researcher": {"href": "https://publications.scilifelab.se/researcher/f9ce233338754c98932dd330d8058fa4.json"}}, {"family": "Grange", "given": "Cristina", "initials": "C", "orcid": "0000-0002-6960-5476", "researcher": {"href": "https://publications.scilifelab.se/researcher/aedebcd5eb2d4a11a3f0e528d6c492d7.json"}}, {"family": "Ceccotti", "given": "Elena", "initials": "E"}, {"family": "Prudente", "given": "Diego", "initials": "D", "orcid": "0009-0003-2205-6515", "researcher": {"href": "https://publications.scilifelab.se/researcher/d1915c75b4524d33a481939486444234.json"}}, {"family": "Cedrino", "given": "Massimo", "initials": "M"}, {"family": "Bucchianico", "given": "Sebastiano Di", "initials": "SD", "orcid": "0000-0002-6396-892X", "researcher": {"href": "https://publications.scilifelab.se/researcher/22ab671e103c40038515391da27d859c.json"}}, {"family": "Ryffel", "given": "Bernhard", "initials": "B", "orcid": "0000-0003-2897-8230", "researcher": {"href": "https://publications.scilifelab.se/researcher/996618de798542e2b0a50d1a73d4772a.json"}}, {"family": "Quesniaux", "given": "Valerie", "initials": "V", "orcid": "0000-0003-2907-7995", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ee4a59410e94f6597c4c232f3499ac9.json"}}, {"family": "Togbe", "given": "Dieudonnee", "initials": "D", "orcid": "0000-0001-6658-414X", "researcher": {"href": "https://publications.scilifelab.se/researcher/466fb8d8fa494b95a7c81a0d4929ed4e.json"}}, {"family": "Huaux", "given": "Francois", "initials": "F", "orcid": "0000-0002-4048-7605", "researcher": {"href": "https://publications.scilifelab.se/researcher/e8bb936610bd4d91ae9c2f7ec3114563.json"}}, {"family": "Wilmot", "given": "Juliet", "initials": "J"}, {"family": "Lallo", "given": "Eleonora", "initials": "E"}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J", "orcid": "0000-0001-9195-9249", "researcher": {"href": "https://publications.scilifelab.se/researcher/0cbcaf6b5698411c92e0de9e8fcf390f.json"}}, {"family": "Dominici", "given": "Massimo", "initials": "M", "orcid": "0000-0002-4007-1503", "researcher": {"href": "https://publications.scilifelab.se/researcher/a8aba4a925cb4420bbcca431ceec33bc.json"}}], "type": "posted-content", "published": "2026-04-13", "journal": {"issn-l": null}, "abstract": null, "doi": "10.64898/2026.04.09.717380", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2026-08-11T10:59:04.161Z", "modified": "2026-08-11T10:59:04.660Z"}, {"entity": "publication", "iuid": "a23f30b374a84d92b66bf2a4ee3f39d8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a23f30b374a84d92b66bf2a4ee3f39d8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a23f30b374a84d92b66bf2a4ee3f39d8"}}, "title": "Development of Anti-Inflammatory Extracellular Vesicles by Surface Expression of Syndecan-4.", "authors": [{"family": "Yu", "given": "Lijuan", "initials": "L"}, {"family": "Bergqvist", "given": "Markus", "initials": "M", "orcid": "0009-0003-5716-3716", "researcher": {"href": "https://publications.scilifelab.se/researcher/91d33e374d0642479a80683a989f095a.json"}}, {"family": "Park", "given": "Kyong-Su", "initials": "KS", "orcid": "0000-0003-0902-7800", "researcher": {"href": "https://publications.scilifelab.se/researcher/26e308b29fe144b49f4db27f4b819c18.json"}}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C", "orcid": "0000-0003-1279-1746", "researcher": {"href": "https://publications.scilifelab.se/researcher/e14e17d2cdb24a9f93991d83811c78b9.json"}}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J", "orcid": "0000-0001-9195-9249", "researcher": {"href": "https://publications.scilifelab.se/researcher/0cbcaf6b5698411c92e0de9e8fcf390f.json"}}], "type": "journal article", "published": "2026-04-00", "journal": {"title": "J Extracell Vesicles", "issn": "2001-3078", "volume": "15", "issue": "4", "pages": "e70266", "issn-l": "2001-3078"}, "abstract": "The biological functions of extracellular vesicles (EVs) depend on their cellular source. Further, different subpopulations of EVs from the same cells carry different cargo, but differences in their biological functions are less understood. We here identify a very small EV subpopulation released by HEK293F cells (miniEVs). These EVs, in contrast to the larger EVs, were found to have anti-inflammatory properties. Quantitative proteomics identified a potential anti-inflammatory molecule, Syndecan-4 (SDC4), on the surface of the miniEVs, but not on larger EVs. We engineered HEK293F cells to overexpress SDC4, which results in the molecule being highly expressed in all EV subpopulations. Expression of SDC4, a proteoglycan, also increased the presence of heparan sulfate on the EV surface. Furthermore, these EVs were found to have potent anti-inflammatory effects in vitro, which heparinase treatment could slightly reduce. Furthermore, the SDC4 EVs showed anti-inflammatory effects in vivo in a model of peritonitis. We conclude that HEK293F miniEVs convey anti-inflammatory properties, and SDC4-expressing HEK293F-EV potentially could become an anti-inflammatory therapeutic.", "doi": "10.1002/jev2.70266", "pmid": "41926337", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC13045914"}], "notes": [], "created": "2026-08-11T11:00:22.811Z", "modified": "2026-08-11T11:00:22.900Z"}, {"entity": "publication", "iuid": "57e10bac8d9246b79b45b276e33e467c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/57e10bac8d9246b79b45b276e33e467c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/57e10bac8d9246b79b45b276e33e467c"}}, "title": "Quantitative proteomic and functional comparison of extracellular vesicles from multiple adipose tissue mesenchymal stem cell donors.", "authors": [{"family": "Park", "given": "Kyong-Su", "initials": "KS"}, {"family": "Ha", "given": "Dae Hyun", "initials": "DH"}, {"family": "Lee", "given": "Jun Ho", "initials": "JH"}, {"family": "Ordouzadeh", "given": "Negar", "initials": "N"}, {"family": "Bergqvist", "given": "Markus", "initials": "M"}, {"family": "Lee", "given": "Hyun Ju", "initials": "HJ"}, {"family": "Shin", "given": "Ella", "initials": "E"}, {"family": "Cho", "given": "Byong Seung", "initials": "BS"}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J"}], "type": "journal article", "published": "2026-03-30", "journal": {"title": "Extracell Vesicles Circ Nucleic Acids.", "issn": "2767-6641", "volume": "7", "issue": "1", "pages": "425-440", "issn-l": null}, "abstract": "Aim: Extracellular vesicles (EVs) released by mesenchymal stem cells (MSCs), known as MSC-EVs, have gained attention as potential treatments owing to their immunomodulatory functions. Despite growing clinical interest, donor-to-donor inconsistencies remain key challenges for standardizing MSC-EV production under good manufacturing practice (GMP) conditions. This work aimed to systematically compare the molecular and functional consistency of EVs derived from three independent human adipose tissue-MSC donors. Methods: GMP-grade EVs were initially isolated using tangential flow filtration on a large scale and then characterized by multiple biophysical analyses. To characterize the protein composition of EVs across batches, quantitative proteomic analysis was performed using tandem mass tags and mass spectrometry. For functional validation, an in vitro macrophage inflammation assay was conducted by treating natural lipopolysaccharide-stimulated cells with EVs, and cytokine levels were measured using enzyme-linked immunosorbent assays (ELISA). Results: Quantitative proteomic profiling identified 2,615 proteins, of which 84%-94% were not significantly changed across batches, highlighting a robust core proteome. Notably, 361 membrane-associated proteins were consistently conserved, including transporters, adhesion molecules, and signaling receptors, implicating these components in EV-mediated intercellular communication and immunomodulation. Functional analysis using an in vitro macrophage inflammation model demonstrated that all EV batches reproducibly suppressed pro-inflammatory cytokine production in a dose-dependent manner, with no significant inter-batch differences. Conclusion: Collectively, these findings indicate that MSC-EVs maintain both molecular and functional stability across different donors, and that a conserved proteomic signature underlies their reproducible anti-inflammatory activity. This study provides a foundation for establishing standardized quality criteria and advancing MSC-EVs toward clinical therapeutic applications.", "doi": "10.20517/evcna.2025.173", "pmid": "41983054", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC13074282"}], "notes": [], "created": "2026-08-11T10:58:24.608Z", "modified": "2026-08-11T10:58:24.612Z"}, {"entity": "publication", "iuid": "31948923167e425d9191717a0f3a6c00", "links": {"self": {"href": "https://publications.scilifelab.se/publication/31948923167e425d9191717a0f3a6c00.json"}, "display": {"href": "https://publications.scilifelab.se/publication/31948923167e425d9191717a0f3a6c00"}}, "title": "Tissue-layer-resolved proteome landscape of Crohn's disease strictures highlights potential drivers of fibrosis progression.", "authors": [{"family": "Alfredsson", "given": "Johannes", "initials": "J"}, {"family": "Sihlbom Wallem", "given": "Carina", "initials": "C"}, {"family": "\u00d6stling", "given": "Maja", "initials": "M"}, {"family": "de la Croix", "given": "Hanna", "initials": "H"}, {"family": "Bexe-Lindskog", "given": "Elinor", "initials": "E"}, {"family": "Wick", "given": "Mary Jo", "initials": "MJ"}], "type": "journal article", "published": "2026-03-23", "journal": {"title": "JCI Insight", "issn": "2379-3708", "volume": "11", "issue": "6", "issn-l": "2379-3708"}, "abstract": "The chronic inflammation of Crohn's disease frequently leads to fibrosis and muscular hypertrophy of the intestinal wall. This often culminates in strictures, a serious condition lacking directed therapy. Severe pathological changes occur in the submucosa and muscularis propria intestinal wall layers of strictures, yet stricture-associated proteome changes in these layers is unexplored. We perform unbiased proteomics on submucosa and muscularis propria microdissected from transmural sections of strictured and nonstrictured ileum. Proteome changes in strictured submucosa reflected a transition from homeostasis to tissue remodeling, inflammation, and smooth muscle changes. Top submucosal features included reduced vascular components and lipid metabolism proteins accompanied by increased proteins with immune-, ECM-, or stress-related functions, including CTHRC1, TNC, IL-16, MZB1, and TXNDC5. In parallel, predominant changes in strictured muscularis propria included increased ECM (POSTN) and immune (mast cell CPA3) proteins alongside decreased proteins with lipid metabolic, mitochondrial, or key muscle functions. Finally, trends of differentially expressed proteins along nonstrictured submucosa suggest progressive profibrotic tissue remodeling and muscle expansion as proximity to strictures increases. The comprehensive proteome map presented here offers tissue-layer-resolved insight into the stricture microenvironment and potential drivers of fibrotic disease, providing a valuable resource to fuel biomarker and therapeutic target research.", "doi": "10.1172/jci.insight.202461", "pmid": "41665933", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC13043094"}, {"db": "pii", "key": "202461"}], "notes": [], "created": "2026-08-11T10:49:38.794Z", "modified": "2026-08-11T10:49:38.797Z"}, {"entity": "publication", "iuid": "fa9f76122c8044ada8ef041a32eb19e8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/fa9f76122c8044ada8ef041a32eb19e8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/fa9f76122c8044ada8ef041a32eb19e8"}}, "title": "Electrochemical measurements at human iPSC-derived FOXA2 dopaminergic neurons suggest a role for partial release in presynaptic plasticity.", "authors": [{"family": "Gu", "given": "Chaoyi", "initials": "C"}, {"family": "Lork", "given": "Alicia", "initials": "A"}, {"family": "Majdi", "given": "Soodabeh", "initials": "S"}, {"family": "Rabasco", "given": "Stefania", "initials": "S"}, {"family": "Peng", "given": "Huashan", "initials": "H"}, {"family": "Ni", "given": "Anjie", "initials": "A"}, {"family": "Ernst", "given": "Carl", "initials": "C"}, {"family": "Ewing", "given": "Andrew G", "initials": "AG", "orcid": "0000-0002-2084-0133", "researcher": {"href": "https://publications.scilifelab.se/researcher/c6ecb82dc7a6423fa0876822f5568e1b.json"}}], "type": "journal article", "published": "2026-03-23", "journal": {"title": "QRB Discovery", "issn": "2633-2892", "volume": "7", "pages": "e3", "issn-l": null}, "abstract": "During the past decade, emerging studies using electrochemistry and nanoscale imaging have demonstrated that partial exocytotic release is prevailing in neuroendocrine cell models. However, due to complicated structure and culture process, few studies have been carried out using neurons, especially human neurons. Here, dopamine (DA) release from individual vesicles and DA content stored within vesicles were quantified from induced pluripotent stem cell-derived DA neurons with electrochemical techniques. The results indicate that around 61% of the total vesicular DA content is released from these neurons during exocytosis. The vesicular content quantified in DA neurons is significantly higher than that in undifferentiated neural progenitor cells, owing to the increased appearance of dense-core vesicles that are able to store more DA molecules than the clear vesicles. When the neurons are differentiated with BAY-K8644, which stimulates neuronal maturation as well as DA release, the release fraction rises to 91%. The use of BAY-K8644 can be considered as chronic stimulation and leads to similar effects on exocytosis as repetitive stimulation, which triggers short-term plasticity. This study demonstrates partial release in DA transmission in human neurons and provides a link between neuronal maturation and the formation of plasticity. Furthermore, this work suggests that the fraction of release in exocytosis at human neurons may be a factor in determining plasticity.", "doi": "10.1017/qrd.2026.10019", "pmid": "42063621", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC13125770"}, {"db": "pii", "key": "S2633289226100192"}], "notes": [], "created": "2026-08-11T10:51:34.450Z", "modified": "2026-08-11T10:51:34.507Z"}, {"entity": "publication", "iuid": "0fa6378cce5b4b0698f0702684f6279c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0fa6378cce5b4b0698f0702684f6279c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0fa6378cce5b4b0698f0702684f6279c"}}, "title": "Proteomic analysis of tissue-derived extracellular vesicles shows region-specific molecular changes in a rat model of takotsubo syndrome.", "authors": [{"family": "Zulfaj", "given": "Ermir", "initials": "E"}, {"family": "Nejat", "given": "Amirali", "initials": "A"}, {"family": "Kalani", "given": "Mana", "initials": "M"}, {"family": "Miljanovic", "given": "Azra", "initials": "A"}, {"family": "Ekstr\u00f6m", "given": "Karin", "initials": "K"}, {"family": "Crescitelli", "given": "Rossella", "initials": "R"}, {"family": "Elmahdy", "given": "Ahmed", "initials": "A"}, {"family": "Thorsell", "given": "Annika", "initials": "A"}, {"family": "Olofsson Bagge", "given": "Roger", "initials": "R"}, {"family": "Redfors", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Omerovic", "given": "Elmir", "initials": "E"}], "type": "journal article", "published": "2026-03-10", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "16", "issue": "1", "issn-l": "2045-2322"}, "abstract": "Takotsubo syndrome (TS) is characterized by transient regional wall motion abnormalities (RWMA) of the heart following stress. Extracellular vesicles (EVs) play a significant role in cellular communication and disease pathophysiology, but remain unexplored in TS. Using a high-fidelity rat model of TS induced by isoprenaline infusion (n = 16), we isolated EVs from the tissue of affected apical and unaffected basal segments of the left ventricle at 24 h post-induction. The TS phenotype and cardiac function were assessed using high-resolution echocardiography. EVs were characterized by electron microscopy, western blot, and nanoparticle tracking analysis (NTA). Moreover, EV protein analysis was performed using tandem mass tag (TMT) proteomics. Pure, cup-shaped vesicles ranging from 50 to 500 nm were successfully isolated. NTA revealed lower particle concentrations in EVs isolated from the apex of TS24h hearts compared to their corresponding basal segments. Western blot experiments confirmed the presence of typical EV markers, including Flotillin 1, TSG101, and CD63. We identified 2093 proteins, with 238 differentially expressed (|FC| > 0.58, adj.P < 0.05) proteins between TS-apex and control-apex, and 562 between TS-apex and TS-base, indicating a unique molecular adaptation in the affected apex. Functional enrichment analysis showed increased abundance of proteins associated with immune response, tissue repair, and survival signalling pathways. Proteins related to mitochondrial function showed decreased abundance. Network analysis revealed an association between proteins involved in lipid processes and inflammation. Overall, this study presents the first proteomic characterization of EVs in TS hearts. Our results demonstrate a distinct EV protein abundance profile in the affected apical segments of TS hearts, with marked changes in proteins related to inflammatory responses, tissue repair mechanisms, energy metabolism, and cell survival pathways. This comprehensive proteomic profile of EVs in TS hearts provides potential candidates for therapeutic targets and diagnostic biomarkers, warranting further mechanistic and clinical validation studies.", "doi": "10.1038/s41598-026-42812-5", "pmid": "41807579", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12979827"}, {"db": "pii", "key": "10.1038/s41598-026-42812-5"}], "notes": [], "created": "2026-08-11T11:00:24.853Z", "modified": "2026-08-11T11:00:24.869Z"}, {"entity": "publication", "iuid": "b05f4bb24d8c400eb15febddb7526182", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b05f4bb24d8c400eb15febddb7526182.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b05f4bb24d8c400eb15febddb7526182"}}, "title": "Better reporting is better science: Community-defined minimal reporting requirements for light microscopy.", "authors": [{"family": "Montero Llopis", "given": "Paula", "initials": "P", "orcid": "0000-0002-5983-2296", "researcher": {"href": "https://publications.scilifelab.se/researcher/9fb8e94dd08e4ca9aa6dad39c13ad963.json"}}, {"family": "van Oostende-Triplet", "given": "Chlo\u00eb", "initials": "C", "orcid": "0000-0002-8310-1928", "researcher": {"href": "https://publications.scilifelab.se/researcher/3780910828904c428cdbb158b08de5e6.json"}}, {"family": "Gaudreault", "given": "Nathalie", "initials": "N", "orcid": "0000-0002-9220-5366", "researcher": {"href": "https://publications.scilifelab.se/researcher/c2a75875451c4bb0ab0d96da9d52fd0d.json"}}, {"family": "Strambio De Castillia", "given": "Caterina", "initials": "C", "orcid": "0000-0002-1069-1816", "researcher": {"href": "https://publications.scilifelab.se/researcher/d56f91373ceb40bab6bae2635961bdf5.json"}}, {"family": "Fernandez-Rodriguez", "given": "Julia", "initials": "J", "orcid": "0000-0003-4522-0966", "researcher": {"href": "https://publications.scilifelab.se/researcher/3bd9c743e99d479cb752aeec947acab3.json"}}, {"family": "Martins", "given": "Gabriel", "initials": "G", "orcid": "0000-0002-6506-9776", "researcher": {"href": "https://publications.scilifelab.se/researcher/c04a08e246854401b529158afe9de318.json"}}, {"family": "North", "given": "Alison", "initials": "A", "orcid": "0000-0002-0577-7949", "researcher": {"href": "https://publications.scilifelab.se/researcher/9304cc3d251c4a9d86ed37f38e2446cd.json"}}, {"family": "Acevedo", "given": "Luis", "initials": "L", "orcid": "0000-0002-5082-3182", "researcher": {"href": "https://publications.scilifelab.se/researcher/c7c73329bd87441c90728d3dfad188ba.json"}}, {"family": "Avilov", "given": "Sergiy", "initials": "S", "orcid": "0000-0003-0860-8857", "researcher": {"href": "https://publications.scilifelab.se/researcher/25497ef7230445d9a65ff80f2bd3caa9.json"}}, {"family": "Bertocchi", "given": "Cristina", "initials": "C", "orcid": "0000-0003-0907-1318", "researcher": {"href": "https://publications.scilifelab.se/researcher/c0570143267045ed89697ade5036cca9.json"}}, {"family": "Boehm", "given": "Ulrike", "initials": "U", "orcid": "0000-0001-7471-2244", "researcher": {"href": "https://publications.scilifelab.se/researcher/4c8a69a74a1d4760a424493c109ca0c1.json"}}, {"family": "Cameron", "given": "Lisa", "initials": "L", "orcid": "0000-0002-8477-0285", "researcher": {"href": "https://publications.scilifelab.se/researcher/5fb98535e33944a5b3e30ec9ca812a0c.json"}}, {"family": "Cammer", "given": "Michael", "initials": "M", "orcid": "0000-0003-4930-1739", "researcher": {"href": "https://publications.scilifelab.se/researcher/ee99041ab66345c0a858545d510b9b74.json"}}, {"family": "Cleret-Buhot", "given": "Aur\u00e9lie", "initials": "A", "orcid": "0000-0003-3032-4332", "researcher": {"href": "https://publications.scilifelab.se/researcher/5b599fbc025e43b2aba95e10dbb8794c.json"}}, {"family": "Dietzel", "given": "Steffen", "initials": "S", "orcid": "0000-0001-5725-3242", "researcher": {"href": "https://publications.scilifelab.se/researcher/ac46408300f54301b52a3f3525ac1e5b.json"}}, {"family": "Faklaris", "given": "Orestis", "initials": "O", "orcid": "0000-0001-5965-5405", "researcher": {"href": "https://publications.scilifelab.se/researcher/2857720b036a4963a37d94ac15c6abe0.json"}}, {"family": "Gaboriau", "given": "David", "initials": "D", "orcid": "0000-0003-4047-6487", "researcher": {"href": "https://publications.scilifelab.se/researcher/0767ae351aa04d009cfe23137d0f2951.json"}}, {"family": "Guilbert", "given": "Thomas", "initials": "T", "orcid": "0000-0001-5069-0730", "researcher": {"href": "https://publications.scilifelab.se/researcher/97a3a1881bc94f4596233a238e09802a.json"}}, {"family": "Grunwald", "given": "David", "initials": "D", "orcid": "0000-0001-9067-804X", "researcher": {"href": "https://publications.scilifelab.se/researcher/b46507eeed044d7b9fdf394b0d396edd.json"}}, {"family": "Gu", "given": "Tingting", "initials": "T", "orcid": "0000-0002-0696-0008", "researcher": {"href": "https://publications.scilifelab.se/researcher/2776dd1980da4bad80080a257cba796b.json"}}, {"family": "Halidi", "given": "Nadia", "initials": "N", "orcid": "0000-0003-0613-2365", "researcher": {"href": "https://publications.scilifelab.se/researcher/9994a26aeda440e7b81825398f3c4839.json"}}, {"family": "Hammer", "given": "Mathias", "initials": "M", "orcid": "0000-0002-5771-5694", "researcher": {"href": "https://publications.scilifelab.se/researcher/50f30e1235c9490ea5eea47f9b45e447.json"}}, {"family": "Hartmann", "given": "Hella", "initials": "H", "orcid": "0000-0002-7133-7474", "researcher": {"href": "https://publications.scilifelab.se/researcher/72c2333be302451d882c3f1a7a8b008d.json"}}, {"family": "Heller", "given": "Janosch", "initials": "J", "orcid": "0000-0002-8825-3787", "researcher": {"href": "https://publications.scilifelab.se/researcher/0b23a113601a4ef8858a55f063db217f.json"}}, {"family": "Jambor", "given": "Helena", "initials": "H", "orcid": "0000-0003-3397-1842", "researcher": {"href": "https://publications.scilifelab.se/researcher/4d9c995274164d5298f59dbd5c088ab7.json"}}, {"family": "Koksoy", "given": "Ayse Aslihan", "initials": "AA", "orcid": "0000-0003-3092-5410", "researcher": {"href": "https://publications.scilifelab.se/researcher/cbad4193d35348c9af4d0a1bb8021a6d.json"}}, {"family": "Lacoste", "given": "Judith", "initials": "J", "orcid": "0000-0002-8783-8599", "researcher": {"href": "https://publications.scilifelab.se/researcher/d910c1919e154367bffa2e67d0b014be.json"}}, {"family": "Larsen", "given": "DeLaine", "initials": "D", "orcid": "0000-0002-9689-8454", "researcher": {"href": "https://publications.scilifelab.se/researcher/7f3286ed30244014ae8175d4cd337567.json"}}, {"family": "Le D\u00e9v\u00e9dec", "given": "Sylvia Emmanuelle", "initials": "SE", "orcid": "0000-0002-0615-9616", "researcher": {"href": "https://publications.scilifelab.se/researcher/52914a32566d411e8ef2d07605d8f1fc.json"}}, {"family": "Liu", "given": "Penghuan", "initials": "P", "orcid": "0000-0001-5081-4334", "researcher": {"href": "https://publications.scilifelab.se/researcher/a9c249a4839843279f9c95da4ca3aebc.json"}}, {"family": "Moore", "given": "Josh", "initials": "J", "orcid": "0000-0003-4028-811X", "researcher": {"href": "https://publications.scilifelab.se/researcher/18cb52a735fd44ce844af5968836bf87.json"}}, {"family": "Nelson", "given": "Glyn", "initials": "G", "orcid": "0000-0002-1895-4772", "researcher": {"href": "https://publications.scilifelab.se/researcher/e100d899ae034300b2b02acb18e7230e.json"}}, {"family": "Nelson", "given": "Michael", "initials": "M", "orcid": "0000-0003-0480-5597", "researcher": {"href": "https://publications.scilifelab.se/researcher/3897b6add2a340e19ad1e051f08931c5.json"}}, {"family": "Norlin", "given": "Nils", "initials": "N", "orcid": "0000-0003-1970-3198", "researcher": {"href": "https://publications.scilifelab.se/researcher/904d237ef4cb45fc9c3284095c227f6c.json"}}, {"family": "Parslow", "given": "Adam", "initials": "A", "orcid": "0000-0002-9868-6914", "researcher": {"href": "https://publications.scilifelab.se/researcher/c96e876d9fde4543b3f1401cdeb78f91.json"}}, {"family": "Payne-Dwyer", "given": "Alexander L", "initials": "AL", "orcid": "0000-0001-8802-352X", "researcher": {"href": "https://publications.scilifelab.se/researcher/719a8aba6ac2413bb571dbc252c3556d.json"}}, {"family": "Peterson", "given": "John", "initials": "J", "orcid": "0000-0002-5528-8561", "researcher": {"href": "https://publications.scilifelab.se/researcher/797076dcf1304650b49aa20522cab843.json"}}, {"family": "Podder", "given": "Santosh", "initials": "S", "orcid": "0000-0003-0576-4598", "researcher": {"href": "https://publications.scilifelab.se/researcher/e1dcfd06eb5841d380d14e4a9f8e4fbf.json"}}, {"family": "Ravasio", "given": "Andrea", "initials": "A", "orcid": "0000-0001-7835-5133", "researcher": {"href": "https://publications.scilifelab.se/researcher/230b8bbce5a34d3f97d463e6c7201404.json"}}, {"family": "Rosa-Molinar", "given": "Eduardo", "initials": "E", "orcid": "0000-0003-2057-8937", "researcher": {"href": "https://publications.scilifelab.se/researcher/0636fdc2955b467ba54cdfb828aa897f.json"}}, {"family": "Schroth-Diez", "given": "Britta", "initials": "B", "orcid": "0000-0002-4908-5952", "researcher": {"href": "https://publications.scilifelab.se/researcher/64d71204d62442b88b5e1a4b3cc5f19d.json"}}, {"family": "Selchow", "given": "Olaf", "initials": "O", "orcid": "0009-0005-4110-9373", "researcher": {"href": "https://publications.scilifelab.se/researcher/6ca99855c87a4298b366c6faff96ddc9.json"}}, {"family": "Srinivasan", "given": "Sathya", "initials": "S", "orcid": "0000-0002-5386-8722", "researcher": {"href": "https://publications.scilifelab.se/researcher/b5f7cae0ad8e49b2a932ab22bf911fb6.json"}}, {"family": "Taatjes", "given": "Douglas", "initials": "D", "orcid": "0000-0003-1903-983X", "researcher": {"href": "https://publications.scilifelab.se/researcher/c6ea5eaf638d44878c83087e2dded63a.json"}}, {"family": "Vonderstein", "given": "Kirstin", "initials": "K", "orcid": "0000-0002-1437-413X", "researcher": {"href": "https://publications.scilifelab.se/researcher/f021e58f6e754ef2b5f861ba724549cf.json"}}, {"family": "Walther", "given": "Christa", "initials": "C", "orcid": "0000-0002-8962-3102", "researcher": {"href": "https://publications.scilifelab.se/researcher/7af103f5623f4437bbc47135ff45b381.json"}}, {"family": "Nitschke", "given": "Roland", "initials": "R", "orcid": "0000-0002-9397-8475", "researcher": {"href": "https://publications.scilifelab.se/researcher/898e19916e4a4837a86226d735ff1ed8.json"}}], "type": "journal article", "published": "2026-03-02", "journal": {"title": "J. Cell Biol.", "issn": "1540-8140", "volume": "225", "issue": "3", "issn-l": "0021-9525"}, "abstract": "Incomplete reporting of microscopy methods undermines transparency, reproducibility, and data reuse. Despite recent initiatives, comprehensive, broadly endorsed, and accessible reporting guidelines are still lacking. Here, we present a bare minimal microscopy reporting requirements checklist that integrates human- and machine-readable input to provide clear, actionable guidance for researchers, reviewers, and publishers and to advance community standards in microscopy.", "doi": "10.1083/jcb.202601032", "pmid": "41739099", "labels": {"Integrated Microscopy Technologies Gothenburg": "Technology development"}, "xrefs": [{"db": "pii", "key": "281525"}], "notes": [], "created": "2026-08-11T10:57:29.584Z", "modified": "2026-08-11T10:57:31.552Z"}, {"entity": "publication", "iuid": "f4dd6f4e72c44ce79de4a204cb9e576f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f4dd6f4e72c44ce79de4a204cb9e576f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f4dd6f4e72c44ce79de4a204cb9e576f"}}, "title": "Bifidobacterium longum and prebiotic interventions restore early-life high-fat/high-sugar diet-induced alterations in feeding behavior in adult mice.", "authors": [{"family": "Cuesta-Marti", "given": "Cristina", "initials": "C", "orcid": "0000-0001-5801-9394", "researcher": {"href": "https://publications.scilifelab.se/researcher/baa384b0b54341da8f2fac9a3be4e166.json"}}, {"family": "Ponce-Espa\u00f1a", "given": "Eduardo", "initials": "E", "orcid": "0000-0001-6197-0041", "researcher": {"href": "https://publications.scilifelab.se/researcher/7779d0962b754413bf98bf72df3c6f61.json"}}, {"family": "Uhlig", "given": "Friederike", "initials": "F", "orcid": "0000-0001-7441-1951", "researcher": {"href": "https://publications.scilifelab.se/researcher/cda6ce181595476fb905e8a971959470.json"}}, {"family": "Stoltenborg", "given": "Iris", "initials": "I"}, {"family": "Wasiewska", "given": "Luiza A", "initials": "LA"}, {"family": "Kareem", "given": "Lamiah", "initials": "L"}, {"family": "Hedayatpour", "given": "Dara", "initials": "D"}, {"family": "Olavarr\u00eda-Ram\u00edrez", "given": "Loreto", "initials": "L"}, {"family": "Rosell-Cardona", "given": "Cristina", "initials": "C", "orcid": "0000-0003-3627-9413", "researcher": {"href": "https://publications.scilifelab.se/researcher/0c9cea7c6c1d4545a15ee0cd9b703ce5.json"}}, {"family": "Bastiaanssen", "given": "Thomaz F S", "initials": "TFS", "orcid": "0000-0001-6891-734X", "researcher": {"href": "https://publications.scilifelab.se/researcher/08055799d14e4bbd85a416143fa065a8.json"}}, {"family": "Tofani", "given": "Gabriel S S", "initials": "GSS", "orcid": "0009-0008-5140-1628", "researcher": {"href": "https://publications.scilifelab.se/researcher/005f2680b1cc42bcac7d0cf7ef10abcd.json"}}, {"family": "Valderrama", "given": "Benjamin", "initials": "B"}, {"family": "Vlckova", "given": "Klara", "initials": "K"}, {"family": "Dickson", "given": "Suzanne L", "initials": "SL"}, {"family": "Lavelle", "given": "Aonghus", "initials": "A"}, {"family": "Stanton", "given": "Catherine", "initials": "C", "orcid": "0000-0002-6724-7011", "researcher": {"href": "https://publications.scilifelab.se/researcher/2a59c196549c4625a3f9c6a3ced9da9c.json"}}, {"family": "Ross", "given": "R Paul", "initials": "RP", "orcid": "0000-0003-4876-8839", "researcher": {"href": "https://publications.scilifelab.se/researcher/14f7fc4e0f094aafaee64d2c3af894b3.json"}}, {"family": "Cryan", "given": "John F", "initials": "JF", "orcid": "0000-0001-5887-2723", "researcher": {"href": "https://publications.scilifelab.se/researcher/ef7ae90db89f49d88cc0faa058709615.json"}}, {"family": "Dinan", "given": "Timothy G", "initials": "TG", "orcid": "0000-0002-2316-7220", "researcher": {"href": "https://publications.scilifelab.se/researcher/89397a01761945b99d2b12569330cfca.json"}}, {"family": "Clarke", "given": "Gerard", "initials": "G", "orcid": "0000-0001-9771-3979", "researcher": {"href": "https://publications.scilifelab.se/researcher/498e0de5b9094934a529b60992ff093c.json"}}, {"family": "O'Mahony", "given": "Siobhain M", "initials": "SM"}, {"family": "Schellekens", "given": "Harri\u00ebt", "initials": "H", "orcid": "0000-0002-6065-3797", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd4d0977b2c34cd98a15e6b65acdffa7.json"}}], "type": "journal article", "published": "2026-02-24", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "17", "issue": "1", "issn-l": "2041-1723"}, "abstract": "An unhealthy diet disrupts feeding behavior and the gut microbiota, but whether early-life dietary effects persist, or can be restored later in life, remains unclear. We investigated whether microbiota-targeted interventions (FOS + GOS or Bifidobacterium longum APC1472) could restore early-life high-fat/high-sugar (HFHS) diet-induced feeding alterations in adult female and male mice. HFHS exposure exclusively in early-life induced persistent, sex-specific feeding alterations in adult mice, despite normalized body weight. Early-life HFHS diet reduced hypothalamic cells expressing feeding-related markers (POMC, GHSR, PNOC, NOD2) in adult mice. Females were more vulnerable, with reduced LEPR+ cells and disrupted arginine/tryptophan metabolism, while males showed impaired peptidoglycan sensing and steroid metabolism. We show that microbiota interventions restore these effects via distinct mechanisms. FOS + GOS induced extensive microbiome compositional shifts and sex-specific restoration of gut-brain pathways, while B. longum APC1472 induced greater behavioral restoration with minimal microbiome compositional changes. These findings highlight sex-specific vulnerabilities and mechanism-dependent therapeutic potential of microbiota-based interventions after exposure to early-life unhealthy diets.", "doi": "10.1038/s41467-026-68968-2", "pmid": "41735265", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12932662"}, {"db": "pii", "key": "10.1038/s41467-026-68968-2"}], "notes": [], "created": "2026-08-11T10:49:43.217Z", "modified": "2026-08-11T10:49:44.298Z"}, {"entity": "publication", "iuid": "a51aace6039f4479909a5aafa46886fb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a51aace6039f4479909a5aafa46886fb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a51aace6039f4479909a5aafa46886fb"}}, "title": "Proteomic and Lipidomic Profiling of Immune Cell\u2010Derived Subpopulations of Extracellular Vesicles", "authors": [{"family": "Lischnig", "given": "Anna", "initials": "A", "orcid": "0000-0001-7742-6905", "researcher": {"href": "https://publications.scilifelab.se/researcher/0c26ce2f15ee46a9b19d59ebd3af7b96.json"}}, {"family": "Karimi", "given": "Nasibeh", "initials": "N", "orcid": "0000-0003-1499-6876", "researcher": {"href": "https://publications.scilifelab.se/researcher/14632eec875c42038aa0b6983e0ec107.json"}}, {"family": "Larsson", "given": "Per", "initials": "P", "orcid": "0000-0002-0456-8192", "researcher": {"href": "https://publications.scilifelab.se/researcher/d642894225474576b4a7c055fa7cb963.json"}}, {"family": "Ekstr\u00f6m", "given": "Karin", "initials": "K", "orcid": "0000-0001-7808-4572", "researcher": {"href": "https://publications.scilifelab.se/researcher/d1922e7379bb4a5ca81b7db180a2d694.json"}}, {"family": "Crescitelli", "given": "Rossella", "initials": "R", "orcid": "0000-0002-1714-3169", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d4b955f26ca4a679deb090e30d0ccf1.json"}}, {"family": "Olin", "given": "Anna\u2010Carin", "initials": "A"}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C", "orcid": "0000-0003-1279-1746", "researcher": {"href": "https://publications.scilifelab.se/researcher/e14e17d2cdb24a9f93991d83811c78b9.json"}}], "type": "journal-article", "published": "2026-01-10", "journal": {"title": "Proteomics", "issn": "1615-9853", "issn-l": null, "volume": null, "issue": null, "pages": "e70096"}, "abstract": "Extracellular vesicles (EVs) are heterogeneous and play important roles in intercellular communication, contributing to physiological and pathological processes. Since few markers currently exist to differentiate subtypes of EVs, this study aimed to determine proteomic and lipidomic differences among four EV subpopulations. Large and small EVs (L-EVs and S-EVs) were isolated from human mast cells (HMC-1) and monocytes (THP-1) by differential ultracentrifugation and then further separated by density cushions into two different densities [low-density (LD) and high-density (HD)]. L-EVs were pelleted at 16,500 \u00d7 g, and S-EVs were pelleted at 118,000 \u00d7 g. LD EVs were collected at 1.079-1.146 g/mL, while HD EVs were collected at 1.146-1.185 g/mL. The morphology, size and yield of EVs were determined by TEM and western blot. The proteome and lipidome of the EV subpopulations were determined with mass spectrometry. A total of 5364 proteins were quantified, and L-EVs LD were enriched in mitochondrial proteins such as TIMM/TOMM and MICOS proteins, while L-EVs HD were enriched in cytoskeleton- and cytokinesis-associated proteins, such as KIF proteins. S-EVs LD were enriched in tetraspanins, ADAM10 and ESCRT machinery proteins, while S-EVs HD were enriched in proteins commonly viewed as contaminants, such as histones, complement factors and collagen. Proteins involved in membrane trafficking between the plasma membrane and organelles, such as adaptor protein complexes, the conserved oligomeric Golgi complex, the trafficking protein particle complex, sortin-nexins, TBC1 domain proteins and coatomer subunits, were expressed at similar levels across all EV subtypes. Furthermore, 107 lipids were quantified, and phosphatidylethanolamine (PE) was less abundant in L-EVs LD as compared to the other EV subtypes, while ceramides were enriched in L-EVs as compared to S-EVs.This study demonstrates that there is a core proteome and lipidome that is similar across all four EV subtypes, but importantly, it also shows that a portion of the proteome and lipidome differs in EV subpopulations separated based on size and density. We suggest that these could be important markers in future EV studies and that they may reflect a different biogenesis and EV function.", "doi": "10.1002/pmic.70096", "pmid": "41518059", "labels": {"Glycoproteomics and MS Proteomics": "Service", "Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2026-01-27T13:33:15.036Z", "modified": "2026-02-11T12:53:10.765Z"}, {"entity": "publication", "iuid": "82faa0d5440442c5abc41cd9b2d6eef2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/82faa0d5440442c5abc41cd9b2d6eef2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/82faa0d5440442c5abc41cd9b2d6eef2"}}, "title": "Plasma extracellular vesicles reflect response and prognosis in patients with breast cancer undergoing neoadjuvant treatment.", "authors": [{"family": "Ekstr\u00f6m", "given": "Karin", "initials": "K", "orcid": "0000-0001-7808-4572", "researcher": {"href": "https://publications.scilifelab.se/researcher/d1922e7379bb4a5ca81b7db180a2d694.json"}}, {"family": "Riaz", "given": "Nazia", "initials": "N"}, {"family": "Larsson", "given": "Karolina", "initials": "K"}, {"family": "Nemeth", "given": "Afrodite", "initials": "A"}, {"family": "Crescitelli", "given": "Rossella", "initials": "R"}, {"family": "Linderholm", "given": "Barbro", "initials": "B"}, {"family": "Olofsson Bagge", "given": "Roger", "initials": "R"}], "type": "journal article", "published": "2026-01-09", "journal": {"title": "Breast Cancer Res.", "issn": "1465-542X", "volume": "28", "issue": "1", "pages": "22", "issn-l": "1465-5411"}, "abstract": "BACKGROUND: Extracellular vesicles (EVs) are emerging as non-invasive biomarkers in cancer, but their role in monitoring the response to neoadjuvant systemic treatment (NST) in patients with breast cancer remains unclear. This study aimed to assess whether EV concentration and surface marker profiles in plasma reflect treatment response and clinical outcome in patients with early-stage breast cancer receiving NST. METHODS: Plasma samples were collected from 59 patients with luminal B-like, HER2-positive, or triple-negative breast cancer before and after NST. EVs were isolated by size exclusion chromatography and characterized by nanoparticle tracking analysis, electron microscopy, Western blotting, and MACSPlex surface marker profiling. Paired samples were available for 29 patients, allowing longitudinal analysis. RESULTS: Patients who achieved pathological complete response (pCR) had significantly lower baseline EV concentrations than those with residual disease. Post-treatment EV levels were also lower in patients who remained free from distant metastasis and had improved breast cancer-specific survival. EV surface marker profiling revealed that CD69, CD29, and CD49e were reduced after NST, whereas CD44 was increased. Notably, EpCAM levels increased specifically in non-PCR patients, suggesting persistent tumor-derived EV release, whereas SSEA-4 levels increased only in patients who achieved pCR. Although EV concentrations and markers differed by subtype and outcome, changes in EV levels following NST were not independently predictive of prognosis. CONCLUSIONS: These findings support the potential of plasma-derived EVs as dynamic biomarkers of treatment response, and suggest possible prognostic relevance in breast cancer. Validation in larger, independent cohorts is needed to assess their clinical applicability.", "doi": "10.1186/s13058-025-02209-0", "pmid": "41514466", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12849309"}, {"db": "pii", "key": "10.1186/s13058-025-02209-0"}], "notes": [], "created": "2026-08-11T10:32:15.539Z", "modified": "2026-08-11T10:32:15.923Z"}, {"entity": "publication", "iuid": "d04a1245b8a64bcf85b5f5db5267df3a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d04a1245b8a64bcf85b5f5db5267df3a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d04a1245b8a64bcf85b5f5db5267df3a"}}, "title": "Electron Tomography-Based Reconstruction of Extracellular Vesicles in Tissue", "authors": [{"family": "Micaroni", "given": "Massimo", "initials": "M"}, {"family": "Berndtsson", "given": "Jens", "initials": "J"}, {"family": "Urz\u00ec", "given": "Ornella", "initials": "O"}, {"family": "Crescitelli", "given": "Rossella", "initials": "R"}], "type": "book-chapter", "published": "2026-00-00", "journal": {"issn": "0893-2336", "pages": "321-336", "issn-l": null}, "abstract": null, "doi": "10.1007/978-1-0716-4905-3_14", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Technology development"}, "xrefs": [], "notes": [], "created": "2026-08-11T10:54:13.486Z", "modified": "2026-08-11T10:54:13.492Z"}, {"entity": "publication", "iuid": "2c984cc0dbff42e6873efdc97db17297", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2c984cc0dbff42e6873efdc97db17297.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2c984cc0dbff42e6873efdc97db17297"}}, "title": "Impact of hydrogen peroxide photolysis on viable bacterial count and composition of in vivo dental biofilm-an ex vivo study.", "authors": [{"family": "Shirato", "given": "Midori", "initials": "M"}, {"family": "Lehrkinder", "given": "Anna", "initials": "A"}, {"family": "Nakamura", "given": "Keisuke", "initials": "K"}, {"family": "Kanno", "given": "Taro", "initials": "T"}, {"family": "Lingstr\u00f6m", "given": "Peter", "initials": "P"}, {"family": "\u00d6rtengren", "given": "Ulf", "initials": "U"}], "type": "journal article", "published": "2025-12-30", "journal": {"title": "BMC Oral Health", "issn": "1472-6831", "issn-l": null}, "abstract": null, "doi": "10.1186/s12903-025-07588-6", "pmid": "41469638", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s12903-025-07588-6"}], "notes": [], "created": "2026-01-12T10:07:18.863Z", "modified": "2026-01-25T08:39:00.177Z"}, {"entity": "publication", "iuid": "e8c58caebc5a495ab34dffe3cbaea1a0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e8c58caebc5a495ab34dffe3cbaea1a0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e8c58caebc5a495ab34dffe3cbaea1a0"}}, "title": "Single recipient cell tracking of tellurium-labeled extracellular vesicle proteomes (TeLEV) identifies EV-driven immunomodulation", "authors": [{"family": "Bachurski", "given": "Daniel", "initials": "D", "orcid": "0000-0001-9168-9680", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f3955354a5b4db1975680eafdc2c997.json"}}, {"family": "Gholamipoorfard", "given": "Rahil", "initials": "R", "orcid": "0000-0001-8207-7295", "researcher": {"href": "https://publications.scilifelab.se/researcher/943864a091c1466795e02edacb855fe2.json"}}, {"family": "Bu", "given": "Yong Jia", "initials": "YJ", "orcid": "0000-0001-9390-0494", "researcher": {"href": "https://publications.scilifelab.se/researcher/a5d00f647d72480b846148683f141be2.json"}}, {"family": "Hoelker", "given": "Patrick", "initials": "P"}, {"family": "Wessendorf", "given": "Lisa", "initials": "L"}, {"family": "Jestrabek", "given": "Hendrik", "initials": "H"}, {"family": "Schreurs", "given": "Luca D", "initials": "LD"}, {"family": "Stahl", "given": "David", "initials": "D"}, {"family": "Mokhlesi", "given": "Amin", "initials": "A"}, {"family": "G\u00f6del", "given": "Philipp", "initials": "P"}, {"family": "Gaedke", "given": "Felix", "initials": "F"}, {"family": "Ranjbari", "given": "Elias", "initials": "E"}, {"family": "Seyhan", "given": "Selen", "initials": "S"}, {"family": "Resch", "given": "Ulrike", "initials": "U"}, {"family": "Schmidt", "given": "Luisa Marie", "initials": "LM"}, {"family": "Tertel", "given": "Tobias", "initials": "T", "orcid": "0000-0001-8659-8610", "researcher": {"href": "https://publications.scilifelab.se/researcher/af482bab6f514bf3b81e5efb0d2b47c5.json"}}, {"family": "Rose", "given": "France", "initials": "F"}, {"family": "Pinheiro", "given": "Cl\u00e1udio", "initials": "C"}, {"family": "Corona", "given": "Maribel L", "initials": "ML"}, {"family": "von Lom", "given": "Anton", "initials": "A"}, {"family": "vom Stein", "given": "Alexander Frederik", "initials": "AF", "orcid": "0000-0002-6910-7792", "researcher": {"href": "https://publications.scilifelab.se/researcher/5ecdaf193d1b4930bf5dfb65cf6920ab.json"}}, {"family": "Nguyen", "given": "Phuong Hien", "initials": "PH", "orcid": "0000-0002-3249-7264", "researcher": {"href": "https://publications.scilifelab.se/researcher/6ea3272b8f7b4433950fd70c01d15f49.json"}}, {"family": "Reiners", "given": "Katrin S", "initials": "KS"}, {"family": "Hendrix", "given": "An", "initials": "A"}, {"family": "van Niel", "given": "Guillaume", "initials": "G", "orcid": "0000-0002-8651-9705", "researcher": {"href": "https://publications.scilifelab.se/researcher/6a1d365f0f0a4152af6c8ead53f71d77.json"}}, {"family": "Kr\u00fcger", "given": "Marcus", "initials": "M"}, {"family": "Bozek", "given": "Katarzyna", "initials": "K"}, {"family": "Meder", "given": "Lydia", "initials": "L"}, {"family": "Malmberg", "given": "Per", "initials": "P"}, {"family": "Cramer", "given": "Paula", "initials": "P"}, {"family": "Eichhorst", "given": "Barbara", "initials": "B"}, {"family": "Peifer", "given": "Martin", "initials": "M"}, {"family": "Ullrich", "given": "Roland T", "initials": "RT"}, {"family": "Schauss", "given": "Astrid", "initials": "A"}, {"family": "Pallasch", "given": "Christian", "initials": "C"}, {"family": "Br\u00f6ckelmann", "given": "Paul J", "initials": "PJ", "orcid": "0000-0001-9662-9900", "researcher": {"href": "https://publications.scilifelab.se/researcher/507ee132e2ff444790ab2eedf0863689.json"}}, {"family": "Jachimowicz", "given": "Ron D", "initials": "RD"}, {"family": "Preu\u00dfer", "given": "Christian", "initials": "C"}, {"family": "Giebel", "given": "Bernd", "initials": "B"}, {"family": "von Strandmann", "given": "Elke Pogge", "initials": "EP"}, {"family": "Nitz", "given": "Mark", "initials": "M", "orcid": "0000-0001-8078-2265", "researcher": {"href": "https://publications.scilifelab.se/researcher/3fb8811e7d964a439d3c4d610d811cde.json"}}, {"family": "Hallek", "given": "Michael", "initials": "M", "orcid": "0000-0002-7425-4455", "researcher": {"href": "https://publications.scilifelab.se/researcher/491a1b4cafe6445d98f5371258d2601c.json"}}, {"family": "Abedpour", "given": "Nima", "initials": "N"}], "type": "posted-content", "published": "2025-11-03", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2025.11.01.685872", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service", "NanoSIMS": "Service"}, "xrefs": [], "notes": [], "created": "2026-03-10T07:23:40.873Z", "modified": "2026-03-10T14:20:37.651Z"}, {"entity": "publication", "iuid": "b6b00054f2834df095a407814eb3b50c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b6b00054f2834df095a407814eb3b50c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b6b00054f2834df095a407814eb3b50c"}}, "title": "Cryo-EM exposes diverse polymorphism in IAPP mutants to guide the rational design of peptide-based therapeutics.", "authors": [{"family": "Ooi", "given": "Saik Ann", "initials": "SA"}, {"family": "Valli", "given": "Dylan", "initials": "D"}, {"family": "Kuska", "given": "Miko\u0142aj I", "initials": "MI"}, {"family": "Mar\u00ed", "given": "Helena", "initials": "H"}, {"family": "Chaudhary", "given": "Himanshu", "initials": "H"}, {"family": "Wahlgren", "given": "Weixiao Yuan", "initials": "WY"}, {"family": "Westenhoff", "given": "Sebastian", "initials": "S"}, {"family": "Tietze", "given": "Alesia A", "initials": "AA"}, {"family": "Novials", "given": "Anna", "initials": "A"}, {"family": "Servitja", "given": "Joan-Marc", "initials": "JM"}, {"family": "Maj", "given": "Micha\u0142", "initials": "M"}], "type": "journal article", "published": "2025-11-01", "journal": {"title": "J. Mol. Biol.", "issn": "1089-8638", "volume": "437", "issue": "21", "pages": "169405", "issn-l": "0022-2836"}, "abstract": "In the pursuit of potential therapeutic agents for type 2 diabetes, non-amyloidogenic forms of the human Islet Amyloid Polypeptide (hIAPP) containing site-specific mutations are of significant interest. In the present study, we dissect the three proline mutations present in the core region of the non-amyloidogenic rat IAPP into single-point mutations at A25P, S28P, and S29P sites. We apply high-resolution cryo-electron microscopy and solve the structures of 6 polymorphs formed by these mutants, revealing the peptide's self-assembly patterns and identifying critical interactions that reinforce these structures in the presence of the \u03b2-sheet breaker. A unique trimeric aggregate with C3 symmetry was identified in the A25P mutant, which we resolved with a 3.05 \u00c5 resolution, while asymmetric trimeric assemblies were observed in the other mutants. Guided by the high-resolution structural models of A25P and S28P fibrils obtained in our study, we successfully designed novel non-amyloidogenic mutants of IAPP with potential therapeutic value. Our findings demonstrate the immense potential of structure-based approaches in developing effective therapeutics against amyloid diseases.", "doi": "10.1016/j.jmb.2025.169405", "pmid": "40850490", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service", "Cryo-EM": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "S0022-2836(25)00471-1"}], "notes": [], "created": "2025-11-05T13:58:49.739Z", "modified": "2025-11-28T10:44:05.239Z"}, {"entity": "publication", "iuid": "388fe736e91941cd9ccb66a502243168", "links": {"self": {"href": "https://publications.scilifelab.se/publication/388fe736e91941cd9ccb66a502243168.json"}, "display": {"href": "https://publications.scilifelab.se/publication/388fe736e91941cd9ccb66a502243168"}}, "title": "Intracellular Regulation of a Serotonin-Gated Ion Channel Links Receptor Trafficking to Memory", "authors": [{"family": "Cesar", "given": "Leona", "initials": "L", "orcid": "0000-0002-4480-2000", "researcher": {"href": "https://publications.scilifelab.se/researcher/18e4da37bd9c45bb998d2f1f20af2036.json"}}, {"family": "Zabeo", "given": "Davide", "initials": "D", "orcid": "0000-0002-5912-4601", "researcher": {"href": "https://publications.scilifelab.se/researcher/03943200c1ae493ab8b7d6886d0af356.json"}}, {"family": "Aspholm", "given": "Emelie", "initials": "E", "orcid": "0000-0001-5878-0722", "researcher": {"href": "https://publications.scilifelab.se/researcher/45811e98fea84e979a0f75adac508749.json"}}, {"family": "Panagaki", "given": "Dimitra", "initials": "D"}, {"family": "H\u00f6\u00f6g", "given": "Johanna Louise", "initials": "JL", "orcid": "0000-0003-2162-3816", "researcher": {"href": "https://publications.scilifelab.se/researcher/f1eaedff964f4060ae6e69f59cad4521.json"}}, {"family": "Morud", "given": "Julia", "initials": "J", "orcid": "0000-0003-1925-5938", "researcher": {"href": "https://publications.scilifelab.se/researcher/d41dc497590f451994c8164a67045c6c.json"}}], "type": "posted-content", "published": "2025-10-27", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2025.10.27.684756", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2026-01-12T10:07:21.362Z", "modified": "2026-01-12T10:07:21.740Z"}, {"entity": "publication", "iuid": "1385430ef1d340e8841c2a15aec35a0e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1385430ef1d340e8841c2a15aec35a0e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1385430ef1d340e8841c2a15aec35a0e"}}, "title": "Computer Vision-Assisted Data Analysis for Correlative Electron Microscopy and Secondary Ion Mass Spectrometry Imaging.", "authors": [{"family": "du Toit", "given": "Andr\u00e9", "initials": "A"}, {"family": "Lork", "given": "Alicia A", "initials": "AA"}, {"family": "Ernst", "given": "Carl", "initials": "C"}, {"family": "Phan", "given": "Nhu T N", "initials": "NTN", "orcid": "0000-0002-3576-0494", "researcher": {"href": "https://publications.scilifelab.se/researcher/6fa50d61430943a6af068ef05736ea4a.json"}}], "type": "journal article", "published": "2025-10-21", "journal": {"title": "Anal. Chem.", "issn": "1520-6882", "volume": "97", "issue": "41", "pages": "22807-22816", "issn-l": "0003-2700"}, "abstract": "Correlative imaging is a powerful analytical approach in bioimaging, as it offers complementary information on the samples measured by different modalities. Particularly, correlative transmission electron microscopy (EM) and nanoscale secondary ion mass spectrometry (NanoSIMS) imaging enable high-resolution morphological and chemical analysis at the subcellular level. However, manual segmentation and correlation of regions of interest (ROIs) in large EM and NanoSIMS data sets are time-consuming, prone to user bias, and limited in throughput. To address this, we developed a computer vision-assisted image analysis pipeline for automatic classification and segmentation of subcellular organelles in EM images, enabling rapid and reproducible correlation with NanoSIMS ion data. Using human neuronal progenitor cells (hNPCs) and differentiated postmitotic neurons, we trained a YOLOv8 deep learning model to recognize six major organelle types. The pipeline included EM image preprocessing, segmentation via YOLOv8, morphological filtering, and image registration with NanoSIMS ion maps. Performance evaluation demonstrated a robust model accuracy. We applied the pipeline to measure 15N-leucine abundance to study protein turnover in single organelles across different cell states. Results showed distinct turnover dynamics among organelles, with slower turnover observed in differentiated neurons compared to hNPCs. The automated pipeline significantly reduced the analysis time (from hours to minutes) while maintaining consistency with manual segmentation. Our approach demonstrates how computer vision can streamline correlative imaging workflows, improve data quality, and enable deeper insights into subcellular processes such as protein turnover, making it especially valuable for SIMS users and broader bioimaging applications.", "doi": "10.1021/acs.analchem.5c04489", "pmid": "41076583", "labels": {"Integrated Microscopy Technologies Gothenburg": "Technology development", "NanoSIMS": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12547856"}], "notes": [], "created": "2026-03-09T17:41:55.015Z", "modified": "2026-03-10T14:20:43.776Z"}, {"entity": "publication", "iuid": "fa1f2b26ed3949e2bdbd3c28dd0edf08", "links": {"self": {"href": "https://publications.scilifelab.se/publication/fa1f2b26ed3949e2bdbd3c28dd0edf08.json"}, "display": {"href": "https://publications.scilifelab.se/publication/fa1f2b26ed3949e2bdbd3c28dd0edf08"}}, "title": "Cryo-EM structure of CLCA1 identifies CLCA1 as a founding member of a novel metzincin family", "authors": [{"family": "Nystr\u00f6m", "given": "Elisabeth", "initials": "E", "orcid": "0000-0002-6970-7894", "researcher": {"href": "https://publications.scilifelab.se/researcher/09bd302f8a1341f6a1a5aaf3bfe94a94.json"}}, {"family": "van der Post", "given": "Sjoerd", "initials": "S", "orcid": "0000-0002-7965-5311", "researcher": {"href": "https://publications.scilifelab.se/researcher/26adc68875cb4cb08bcf969868b42890.json"}}, {"family": "Barrett", "given": "Doireann Bradley", "initials": "DB"}, {"family": "Raba", "given": "Grete", "initials": "G", "orcid": "0000-0002-7764-3878", "researcher": {"href": "https://publications.scilifelab.se/researcher/e9c5c71873aa4992bec09f9f6aabba5c.json"}}, {"family": "Pelaseyed", "given": "Thaher", "initials": "T", "orcid": "0000-0002-6434-3913", "researcher": {"href": "https://publications.scilifelab.se/researcher/9dc0aa3d9762420caa7efaaa19c1174b.json"}}, {"family": "Oltean", "given": "Mihai", "initials": "M", "orcid": "0000-0003-3783-5207", "researcher": {"href": "https://publications.scilifelab.se/researcher/60a46e232d2644afbe9a4f3d89316a7a.json"}}, {"family": "Luis", "given": "Ana S", "initials": "AS", "orcid": "0000-0002-5086-7353", "researcher": {"href": "https://publications.scilifelab.se/researcher/06abcf6fc3584357afbd80d6537fdd48.json"}}, {"family": "Trillo-Muyo", "given": "Sergio", "initials": "S", "orcid": "0000-0002-3135-9134", "researcher": {"href": "https://publications.scilifelab.se/researcher/2e6b6b830e9145a2ae3e6c10895acbee.json"}}], "type": "posted-content", "published": "2025-10-18", "journal": {"issn-l": null}, "abstract": null, "doi": "10.1101/2025.10.18.683246", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2026-01-12T10:07:24.335Z", "modified": "2026-01-12T10:07:24.558Z"}, {"entity": "publication", "iuid": "e9e5f0d76e26448ea903e68b1e56373e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e9e5f0d76e26448ea903e68b1e56373e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e9e5f0d76e26448ea903e68b1e56373e"}}, "title": "Heat-affected zone cracking in new 718-type superalloy VDM alloy 780: Effect of solution heat treatments and comparison with alloy 718", "authors": [{"family": "Ariaseta", "given": "Achmad", "initials": "A", "orcid": "0000-0002-9520-0456", "researcher": {"href": "https://publications.scilifelab.se/researcher/c51dbaf873644924be646d70c5d2f45f.json"}}, {"family": "Andersson", "given": "Joel", "initials": "J", "orcid": "0000-0001-9065-0741", "researcher": {"href": "https://publications.scilifelab.se/researcher/bb14103bdd9b4df994ba97e3d17fb1c3.json"}}, {"family": "Ojo", "given": "Olanrewaju", "initials": "O"}], "type": "journal-article", "published": "2025-10-00", "journal": {"title": "Materials &amp; Design", "issn": "0264-1275", "volume": "258", "pages": "114733", "issn-l": null}, "abstract": null, "doi": "10.1016/j.matdes.2025.114733", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service", "NanoSIMS": "Service"}, "xrefs": [], "notes": [], "created": "2026-03-10T07:24:05.465Z", "modified": "2026-03-10T14:20:39.630Z"}, {"entity": "publication", "iuid": "c7985d3e4b4342dd8faf493f01cc6d1b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c7985d3e4b4342dd8faf493f01cc6d1b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c7985d3e4b4342dd8faf493f01cc6d1b"}}, "title": "Corrigendum to \"In vitro study of cold atmospheric plasma-induced proliferation inhibition and morphological changes in head and neck carcinoma cell lines\" [Journal of Dentistry161 (2025) 106007].", "authors": [{"family": "Maravic", "given": "Tatjana", "initials": "T"}, {"family": "Petrucci", "given": "Giulia", "initials": "G"}, {"family": "di Giacomo", "given": "Viviana", "initials": "V"}, {"family": "Mazzitelli", "given": "Claudia", "initials": "C"}, {"family": "Acharya", "given": "Tirtha Raj", "initials": "TR"}, {"family": "Kaushik", "given": "Nagendra Kumar", "initials": "NK"}, {"family": "Choi", "given": "Eun Ha", "initials": "EH"}, {"family": "Rapino", "given": "Monica", "initials": "M"}, {"family": "D'Urso", "given": "Diego", "initials": "D"}, {"family": "Josic", "given": "Uros", "initials": "U"}, {"family": "Caponio", "given": "Vito Carlo Alberto", "initials": "VCA"}, {"family": "Micaroni", "given": "Massimo", "initials": "M"}, {"family": "Mancuso", "given": "Edoardo", "initials": "E"}, {"family": "Russo", "given": "Lucio Lo", "initials": "LL"}, {"family": "Muzio", "given": "Lorenzo Lo", "initials": "LL"}, {"family": "Breschi", "given": "Lorenzo", "initials": "L"}, {"family": "Perrotti", "given": "Vittoria", "initials": "V"}], "type": "published erratum", "published": "2025-09-24", "journal": {"title": "J Dent", "issn": "1879-176X", "pages": "106098", "issn-l": null}, "abstract": null, "doi": "10.1016/j.jdent.2025.106098", "pmid": "40992958", "labels": {"Integrated Microscopy Technologies Gothenburg": "Technology development"}, "xrefs": [{"db": "pii", "key": "S0300-5712(25)00544-5"}], "notes": [], "created": "2025-11-05T13:56:41.915Z", "modified": "2025-11-05T13:56:41.945Z"}, {"entity": "publication", "iuid": "68a7b049174f41e0a725288c665eede5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/68a7b049174f41e0a725288c665eede5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/68a7b049174f41e0a725288c665eede5"}}, "title": "Hot ductility behavior of new Ni-based superalloy G27: Influence of solution annealing on the liquation cracking susceptibility", "authors": [{"family": "Ariaseta", "given": "Achmad", "initials": "A", "orcid": "0000-0002-9520-0456", "researcher": {"href": "https://publications.scilifelab.se/researcher/c51dbaf873644924be646d70c5d2f45f.json"}}, {"family": "Hanning", "given": "Fabian", "initials": "F", "orcid": "0000-0002-1607-9177", "researcher": {"href": "https://publications.scilifelab.se/researcher/6737b910038f4c838703141e08aafd3a.json"}}, {"family": "Andersson", "given": "Joel", "initials": "J", "orcid": "0000-0001-9065-0741", "researcher": {"href": "https://publications.scilifelab.se/researcher/bb14103bdd9b4df994ba97e3d17fb1c3.json"}}, {"family": "Ojo", "given": "Olanrewaju", "initials": "O"}], "type": "journal-article", "published": "2025-09-00", "journal": {"title": "Journal of Materials Research and Technology", "issn": "2238-7854", "volume": "38", "pages": "4133-4149", "issn-l": null}, "abstract": null, "doi": "10.1016/j.jmrt.2025.08.241", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service", "NanoSIMS": "Service"}, "xrefs": [], "notes": [], "created": "2026-03-10T07:24:20.430Z", "modified": "2026-03-10T14:20:41.619Z"}, {"entity": "publication", "iuid": "a572b67791f3483dbb7abb241e1938d3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a572b67791f3483dbb7abb241e1938d3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a572b67791f3483dbb7abb241e1938d3"}}, "title": "An Anti\u2010Myd88 Peptide Synergistically Enhances the Anti\u2010Inflammatory Effects of Extracellular Vesicles from Na\u00efve Umbilical Cord MSC or HEK293F CD24 Overexpressing Cells", "authors": [{"family": "Abas", "given": "Bur\u00e7in \u0130rem", "initials": "B\u0130", "orcid": "0000-0002-1018-5577", "researcher": {"href": "https://publications.scilifelab.se/researcher/941e021f937f43edab7eaed4003cbf7e.json"}}, {"family": "Bergqvist", "given": "Markus", "initials": "M", "orcid": "0009-0003-5716-3716", "researcher": {"href": "https://publications.scilifelab.se/researcher/91d33e374d0642479a80683a989f095a.json"}}, {"family": "Yu", "given": "Lijuan", "initials": "L", "orcid": "0000-0003-3558-3800", "researcher": {"href": "https://publications.scilifelab.se/researcher/8b0b4ca8553144b19c236bc09c1c9b81.json"}}, {"family": "Wang", "given": "Yi", "initials": "Y", "orcid": "0000-0002-4954-6317", "researcher": {"href": "https://publications.scilifelab.se/researcher/272a124e437a4787a233f9010f1b097f.json"}}, {"family": "Gimona", "given": "Mario", "initials": "M", "orcid": "0000-0002-2242-2015", "researcher": {"href": "https://publications.scilifelab.se/researcher/b34548020ae94f38872dc7c79cd44b76.json"}}, {"family": "Park", "given": "Kyong\u2010su", "initials": "K", "orcid": "0000-0003-0902-7800", "researcher": {"href": "https://publications.scilifelab.se/researcher/26e308b29fe144b49f4db27f4b819c18.json"}}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J", "orcid": "0000-0001-9195-9249", "researcher": {"href": "https://publications.scilifelab.se/researcher/0cbcaf6b5698411c92e0de9e8fcf390f.json"}}], "type": "journal-article", "published": "2025-08-29", "journal": {"title": "Adv Materials Inter", "issn": "2196-7350", "issn-l": null}, "abstract": null, "doi": "10.1002/admi.202500252", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2025-11-05T13:25:34.023Z", "modified": "2025-11-05T13:25:34.577Z"}, {"entity": "publication", "iuid": "9b5649744c38405dbf38188c2431d979", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9b5649744c38405dbf38188c2431d979.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9b5649744c38405dbf38188c2431d979"}}, "title": "Smart Microscopy: Current Implementations and a Roadmap for Interoperability", "authors": [{"family": "Hinderling", "given": "Lucien", "initials": "L", "orcid": "0000-0002-3956-9363", "researcher": {"href": "https://publications.scilifelab.se/researcher/1c639b9c76754da490fb7685c24cf81a.json"}}, {"family": "Heil", "given": "Hannah S", "initials": "HS", "orcid": "0000-0003-4279-7022", "researcher": {"href": 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"researcher": {"href": "https://publications.scilifelab.se/researcher/97a3a1881bc94f4596233a238e09802a.json"}}, {"family": "Torro", "given": "R\u00e9my", "initials": "R", "orcid": "0000-0002-4903-8304", "researcher": {"href": "https://publications.scilifelab.se/researcher/4381c9d35c5a4cb599808d36cb4ee491.json"}}, {"family": "Bouchareb", "given": "Otmane", "initials": "O"}, {"family": "Demeautis", "given": "Claire", "initials": "C", "orcid": "0009-0004-7834-9621", "researcher": {"href": "https://publications.scilifelab.se/researcher/fd6befc2ff6f403a983658dd3db99432.json"}}, {"family": "Martin", "given": "C\u00e9lia", "initials": "C"}, {"family": "Brooks", "given": "Scott", "initials": "S", "orcid": "0009-0002-4748-7293", "researcher": {"href": "https://publications.scilifelab.se/researcher/6f747e713465409596e2031272fb84af.json"}}, {"family": "Sisamakis", "given": "Evangelos", "initials": "E"}, {"family": "Grandgirard", "given": "Erwan", "initials": "E", "orcid": "0000-0002-5263-2144", "researcher": {"href": "https://publications.scilifelab.se/researcher/955165560ba34b4dbb883a70f34a16d5.json"}}, {"family": "Mutterer", "given": "Jerome", "initials": "J", "orcid": "0000-0002-0722-5195", "researcher": {"href": "https://publications.scilifelab.se/researcher/55316e9f0e4b42e9b5c4d8bac14dd682.json"}}, {"family": "Oatman", "given": "Harrison", "initials": "H", "orcid": "0000-0002-2699-6374", "researcher": {"href": "https://publications.scilifelab.se/researcher/a6818c59f877414b949e276d5cce74c5.json"}}, {"family": "Toettcher", "given": "Jared", "initials": "J", "orcid": "0000-0002-1546-4030", "researcher": {"href": "https://publications.scilifelab.se/researcher/c5464a4c3a5f4b76a94999c2164af0d0.json"}}, {"family": "Rogov", "given": "Andrii", "initials": "A"}, {"family": "Antonovaite", "given": "Nelda", "initials": "N", "orcid": "0000-0001-9080-0324", "researcher": {"href": "https://publications.scilifelab.se/researcher/30bcb20ca0364be598b3371e5ef62534.json"}}, {"family": "Johansson", "given": "Karl", "initials": "K", "orcid": "0000-0002-4140-2159", "researcher": {"href": "https://publications.scilifelab.se/researcher/ffe93a2e29f54a448becf3d7f82af27d.json"}}, {"family": "Ahnlinde", "given": "Johannes K", "initials": "JK", "orcid": "0000-0002-8136-8928", "researcher": {"href": "https://publications.scilifelab.se/researcher/4d5a19c2b844431bb8539e85491256f1.json"}}, {"family": "Andr\u00e9", "given": "Oscar", "initials": "O", "orcid": "0000-0003-1732-9454", "researcher": {"href": "https://publications.scilifelab.se/researcher/8cb45098164e438f8db95715e2d46a1e.json"}}, {"family": "Nordenfelt", "given": "Philip", "initials": "P", "orcid": "0000-0002-9481-9951", "researcher": {"href": "https://publications.scilifelab.se/researcher/7aa3418ab23a4ec48c037d6d6ddea5b5.json"}}, {"family": "Nordenfelt", "given": "Pontus", "initials": "P", "orcid": "0000-0002-9481-9951", "researcher": {"href": "https://publications.scilifelab.se/researcher/7aa3418ab23a4ec48c037d6d6ddea5b5.json"}}, {"family": "Pfander", "given": "Claudia", "initials": "C", "orcid": "0000-0002-9574-9553", "researcher": {"href": "https://publications.scilifelab.se/researcher/46902321e1c041b992dd455ca966260a.json"}}, {"family": "Reymann", "given": "J\u00fcrgen", "initials": "J"}, {"family": "Lambert", "given": "Talley", "initials": "T", "orcid": "0000-0002-2409-0181", "researcher": {"href": "https://publications.scilifelab.se/researcher/3a3cf6c909954f19960ed2bb3de0b19a.json"}}, {"family": "Cosenza", "given": "Marco R", "initials": "MR", "orcid": "0000-0003-1744-5973", "researcher": {"href": "https://publications.scilifelab.se/researcher/8c2ecb6e752f490f880d193a4cb1f1ee.json"}}, {"family": "Korbel", "given": "Jan O", "initials": "JO", "orcid": "0000-0002-2798-3794", "researcher": {"href": "https://publications.scilifelab.se/researcher/ed72e69cece749b08191bb9367887af8.json"}}, {"family": "Pepperkok", "given": "Rainer", "initials": "R", "orcid": "0000-0002-9762-3583", "researcher": {"href": "https://publications.scilifelab.se/researcher/e93cb4819a6544d9b1350391f545fd0f.json"}}, {"family": "Kapitein", "given": "Lukas C", "initials": "LC", "orcid": "0000-0001-9418-6739", "researcher": {"href": "https://publications.scilifelab.se/researcher/91d00025167d4ccc85878c8195a36f2e.json"}}, {"family": "Pertz", "given": "Olivier", "initials": "O", "orcid": "0000-0001-8579-4919", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ce679783be64951a3c507bf0200f538.json"}}, {"family": "Norlin", "given": "Nils", "initials": "N", "orcid": "0000-0003-1970-3198", "researcher": {"href": "https://publications.scilifelab.se/researcher/904d237ef4cb45fc9c3284095c227f6c.json"}}, {"family": "Halavatyi", "given": "Aliaksandr", "initials": "A", "orcid": "0000-0002-9002-457X", "researcher": {"href": "https://publications.scilifelab.se/researcher/cb2a1680338840d5be54c92ff5efebd2.json"}}, {"family": "Camacho", "given": "Rafael", "initials": "R", "orcid": "0000-0003-2325-6407", "researcher": {"href": "https://publications.scilifelab.se/researcher/6a7a8cfe28634821984b078ce3246343.json"}}], "type": "posted-content", "published": "2025-08-20", "journal": {"title": "biorxiv", "issn": null, "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": null, "doi": "10.1101/2025.08.18.670881", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Technology development"}, "xrefs": [], "notes": [], "created": "2025-11-05T13:52:25.254Z", "modified": "2025-12-18T19:10:58.884Z"}, {"entity": "publication", "iuid": "8a944c22f1ab482e8a31f8af3b240aa9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8a944c22f1ab482e8a31f8af3b240aa9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8a944c22f1ab482e8a31f8af3b240aa9"}}, "title": "An in vivo mimetic liver-lobule-chip (LLoC) for stem cell maturation, and zonation of hepatocyte-like cells on chip.", "authors": [{"family": "Dalsbecker", "given": "Philip", "initials": "P", "orcid": "0000-0002-9762-2935", "researcher": {"href": "https://publications.scilifelab.se/researcher/f9f86bdd978e4ac399fa9da18dba97ae.json"}}, {"family": "Suominen", "given": "Siiri", "initials": "S"}, {"family": "Faridi", "given": "Muhammad Asim", "initials": "MA"}, {"family": "Mahdavi", "given": "Reza", "initials": "R"}, {"family": "Johansson", "given": "Julia", "initials": "J"}, {"family": "Blomqvist", "given": "Charlotte Hamngren", "initials": "CH"}, {"family": "Goks\u00f6r", "given": "Mattias", "initials": "M"}, {"family": "Aalto-Set\u00e4l\u00e4", "given": "Katriina", "initials": "K"}, {"family": "Viiri", "given": "Leena E", "initials": "LE"}, {"family": "Adiels", "given": "Caroline B", "initials": "CB", "orcid": "0000-0002-2403-2213", "researcher": {"href": "https://publications.scilifelab.se/researcher/029f8a8f2f704d358b8743d821c03bd7.json"}}], "type": "journal article", "published": "2025-08-19", "journal": {"title": "Lab Chip", "issn": "1473-0189", "volume": "25", "issue": "17", "pages": "4328-4344", "issn-l": null}, "abstract": "In vitro cell culture models play a crucial role in preclinical drug discovery. To achieve optimal culturing environments and establish physiologically relevant organ-specific conditions, it is imperative to replicate in vivo scenarios when working with primary or induced pluripotent cell types. However, current approaches to recreating in vivo conditions and generating relevant 3D cell cultures still fall short. In this study, we validate a liver-lobule-chip (LLoC) containing 21 artificial liver lobules, each representing the smallest functional unit of the human liver. The LLoC facilitates diffusion-based perfusion via sinusoid-mimetic structures, providing physiologically relevant shear stress exposure and radial nutrient concentration gradients within each lobule. We demonstrate the feasibility of long term cultures (up to 14 days) of viable and functional HepG2 cells in a 3D discoid tissue structure, serving as initial proof of concept. Thereafter, we successfully differentiate sensitive, human induced pluripotent stem cell (iPSC)-derived cells into hepatocyte-like cells over a period of 20 days on-chip, exhibiting advancements in maturity compared to traditional 2D cultures. Further, hepatocyte-like cells cultured in the LLoC exhibit zonated protein expression profiles, indicating the presence of metabolic gradients characteristic of liver lobules. Our results highlight the suitability of the LLoC for long-term discoid tissue cultures, specifically for iPSCs, and their differentiation in a perfused environment. We envision the LLoC as a starting point for more advanced in vitro models, allowing for the combination of multiple liver cell types to create a comprehensive liver model for disease-onchip studies. Ultimately, when combined with stem cell technology, the LLoC offers a promising and robust on-chip liver model that serves as a viable alternative to primary hepatocyte cultures-ideally suited for preclinical drug screening and personalized medicine applications.", "doi": "10.1039/d4lc00509k", "pmid": "40485317", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2025-11-05T13:48:17.697Z", "modified": "2025-11-05T13:48:17.823Z"}, {"entity": "publication", "iuid": "f317e27f226041d0a08da9a63eb7e924", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f317e27f226041d0a08da9a63eb7e924.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f317e27f226041d0a08da9a63eb7e924"}}, "title": "Body weight reduction by increased weight loading in mice is associated with sensory signaling in the dorsal horn of the lumbar spinal cord.", "authors": [{"family": "Anesten", "given": "Fredrik", "initials": "F"}, {"family": "Zlatkovic", "given": "Jovana", "initials": "J"}, {"family": "Ohlsson", "given": "Claes", "initials": "C"}, {"family": "L\u00f6ken", "given": "Line", "initials": "L"}, {"family": "H\u00e4gg", "given": "Daniel", "initials": "D"}, {"family": "Jansson", "given": "John-Olov", "initials": "JO"}], "type": "journal article", "published": "2025-08-16", "journal": {"title": "Neuroscience", "issn": "1873-7544", "volume": "581", "pages": "157-163", "issn-l": null}, "abstract": "Previously, we demonstrated that increased weight loading suppresses body weight and food intake in rodents. Our earlier studies suggested that the hind limbs sense this increased load and transmit signals to the Nucleus of the Solitary Tract (NTS) in the brainstem. However, the pathway of this signal transmission was unclear. To investigate if sensory neurons contribute to this signaling, mice were implanted subcutaneously with two capsules weighing \u223c15 % (Load) or \u223c2.5 % (Control) of their body weight in total. Five days post-implantation, neuronal activation was measured by FosB immunoreactivity. An increase of FosB expression was found in Load mice compared to Control specifically at the lumbar L3-L5 segments in the superficial laminae (I-III) of the dorsal horn (DH). These segments receive input via sensory nerves from deeper parts of the hind limbs. Intrathecal injection of the drug capsaicin, blocking sensory nerve signaling, at L3-L5 attenuated Load-induced FosB expression at the lumbar L3-L5 segments and body weight reduction. In summary, increased weight loading increases FosB expression at segments L3-L5 of the DH and reduces body weight via sensory nerves. We propose that increased weight loading enhances compression of weight-bearing bones in the hind limbs, resulting in sensory nerve transmission to cell bodies in L3-L5, which in turn reduces food intake and body weight.", "doi": "10.1016/j.neuroscience.2025.07.009", "pmid": "40645323", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S0306-4522(25)00771-7"}], "notes": [], "created": "2025-11-05T13:27:12.078Z", "modified": "2025-11-05T13:27:12.191Z"}, {"entity": "publication", "iuid": "8a1c0d0e49ab4ddaaca2551db8330fbc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8a1c0d0e49ab4ddaaca2551db8330fbc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8a1c0d0e49ab4ddaaca2551db8330fbc"}}, "title": "Optimization of the Isolation Method for Large\u2010Scale Production of Synthetic Bacterial Vesicles for Cancer Immunotherapy", "authors": [{"family": "Ordouzadeh", "given": "Negar", "initials": "N"}, {"family": "Crescitelli", "given": "Rossella", "initials": "R"}, {"family": "Zimmer", "given": "Agnes", "initials": "A"}, {"family": "Tj\u00e4rnlund", "given": "Petra", "initials": "P"}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C"}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J"}, {"family": "Park", "given": "Kyong\u2010Su", "initials": "K", "orcid": "0000-0003-0902-7800", "researcher": {"href": "https://publications.scilifelab.se/researcher/26e308b29fe144b49f4db27f4b819c18.json"}}], "type": "journal-article", "published": "2025-08-00", "journal": {"title": "Advanced Therapeutics", "issn": "2366-3987", "volume": "8", "issue": "8", "issn-l": null}, "abstract": null, "doi": "10.1002/adtp.202500084", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2025-11-05T13:58:52.094Z", "modified": "2025-11-05T13:58:52.148Z"}, {"entity": "publication", "iuid": "6a3d8633c23e4f38b7f95ceb3f097594", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6a3d8633c23e4f38b7f95ceb3f097594.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6a3d8633c23e4f38b7f95ceb3f097594"}}, "title": "Single-Entity Resolution Single-Cell Nanosensor Reveals Reactive Oxygen Species at Stress Granules Are Formed by Interfacial Redox Chemistry.", "authors": [{"family": "Gu", "given": "Hui", "initials": "H"}, {"family": "Gu", "given": "Chaoyi", "initials": "C"}, {"family": "Du Toit", "given": "Andre", "initials": "A"}, {"family": "Yu", "given": "Wen", "initials": "W"}, {"family": "Chen", "given": "Michael W", "initials": "MW"}, {"family": "Struckman", "given": "Heather L", "initials": "HL"}, {"family": "Silva", "given": "Jonathan R", "initials": "JR"}, {"family": "Dai", "given": "Yifan", "initials": "Y", "orcid": "0000-0002-1009-5790", "researcher": {"href": "https://publications.scilifelab.se/researcher/278a241ff01846b7913d280926534457.json"}}, {"family": "Ewing", "given": "Andrew G", "initials": "AG", "orcid": "0000-0002-2084-0133", "researcher": {"href": "https://publications.scilifelab.se/researcher/c6ecb82dc7a6423fa0876822f5568e1b.json"}}], "type": "journal article", "published": "2025-07-30", "journal": {"title": "J. Am. Chem. Soc.", "issn": "1520-5126", "volume": "147", "issue": "30", "pages": "27020-27029", "issn-l": "0002-7863"}, "abstract": "The electrochemical activities of biomolecular condensates represent a new fundamental functioning mechanism in biochemistry and cell biology. However, our understanding of the underlying molecular mechanism and the interfacial field-dependent chemical activities remains limited. This is due to the lack of technology to probe such activities in real time and at a single-condensate level. Stress granules (SGs) are membraneless organelles that form in the cytoplasm to adapt to cell stress, which are found to encapsulate reactive oxygen species (ROS) in our lab. Here, we design and implement a collision-based electrochemical nanosensor that enables probing of the redox activities of SGs at a single-condensate level in live cells. We show that ex-vivo separated SGs drive the redox reactions depending on their own interfacial potentials and the constituents of the solution system. Surprisingly, we found that water molecules, rather than solvated oxygen (the main source of ROS produced by a conventional enzyme reaction in cells), are the main chemical origin of the redox activity of SGs. Finally, we demonstrate the application of this electrochemical nanosensor in real-time probing of the generation of hydrogen peroxide from SGs in mammalian cells and show that the electrochemical environment of the cells can regulate the redox activity of SGs. This work uncovers the likely mechanisms encoding nonenzymatic redox activities of SGs and demonstrates a key fundamental technological capability that can be highly useful in exploring the intracellular electroactive pathways of macroscale assemblies.", "doi": "10.1021/jacs.5c09338", "pmid": "40692136", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12314916"}], "notes": [], "created": "2025-11-05T13:50:45.342Z", "modified": "2025-11-05T13:50:45.408Z"}, {"entity": "publication", "iuid": "be2bf86eb5d64f5d95d391903ab5b1cf", "links": {"self": {"href": "https://publications.scilifelab.se/publication/be2bf86eb5d64f5d95d391903ab5b1cf.json"}, "display": {"href": "https://publications.scilifelab.se/publication/be2bf86eb5d64f5d95d391903ab5b1cf"}}, "title": "Development of Anti-Inflammatory Extracellular Vesicles by Surface Expression of Syndecan-4", "authors": [{"family": "Yu", "given": "Lijuan", "initials": "L", "orcid": "0000-0003-3558-3800", "researcher": {"href": "https://publications.scilifelab.se/researcher/8b0b4ca8553144b19c236bc09c1c9b81.json"}}, {"family": "Bergqvist", "given": "Markus", "initials": "M", "orcid": "0009-0003-5716-3716", "researcher": {"href": "https://publications.scilifelab.se/researcher/91d33e374d0642479a80683a989f095a.json"}}, {"family": "Park", "given": "Kyong Su", "initials": "KS", "orcid": "0000-0003-0902-7800", "researcher": {"href": "https://publications.scilifelab.se/researcher/26e308b29fe144b49f4db27f4b819c18.json"}}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C", "orcid": "0000-0003-1279-1746", "researcher": {"href": "https://publications.scilifelab.se/researcher/e14e17d2cdb24a9f93991d83811c78b9.json"}}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J", "orcid": "0000-0001-9195-9249", "researcher": {"href": "https://publications.scilifelab.se/researcher/0cbcaf6b5698411c92e0de9e8fcf390f.json"}}], "type": "posted-content", "published": "2025-07-09", "journal": {"title": "biorxiv", "issn": null, "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": null, "doi": "10.1101/2025.07.05.663259", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2025-11-05T14:10:03.333Z", "modified": "2025-12-18T19:13:20.153Z"}, {"entity": "publication", "iuid": "43ff9ae2ee304005b3b75d388520674e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/43ff9ae2ee304005b3b75d388520674e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/43ff9ae2ee304005b3b75d388520674e"}}, "title": "From Recruitment to Retirement: Research Infrastructure Staff Views on the Diversification of Scientific Career Paths at Universities in Sweden in 2024.", "authors": [{"family": "Schroeder", "given": "Kristen", "initials": "K", "orcid": "0000-0002-6271-4530", "researcher": {"href": "https://publications.scilifelab.se/researcher/79f3c1b13a9844be86fdce0b7f425fb3.json"}}, {"family": "Fern\u00e1ndez-Rodr\u00edguez", "given": "Julia", "initials": "J"}, {"family": "Jenmalm-Jensen", "given": "Annika", "initials": "A"}, {"family": "Lundgren-Gawell", "given": "Josefin", "initials": "J"}, {"family": "Sandin", "given": "Sara", "initials": "S"}, {"family": "Stadler", "given": "Charlotte", "initials": "C", "orcid": "0000-0002-6781-1938", "researcher": {"href": "https://publications.scilifelab.se/researcher/2db3b27c7d7143cbacc8c1dd8ac90a31.json"}}, {"family": "Lindvall", "given": "Jessica M", "initials": "JM", "orcid": "0000-0002-5042-8481", "researcher": {"href": "https://publications.scilifelab.se/researcher/78debae1bc714b11a97ecf9e9656f1eb.json"}}], "type": "journal article", "published": "2025-07-04", "journal": {"title": "F1000Res", "issn": "2046-1402", "issn-l": "2046-1402", "volume": "14", "issue": null, "pages": "652"}, "abstract": "There is an ongoing need to develop diverse career paths that support the vital contributions of staff scientists, research engineers, scientific officers, and other knowledge professionals in scientific discovery. Research infrastructures and core facilities have a particular need to support sustainable and diverse careers, as they either employ - if being a legal entity - or daily manage research professionals in a broad variety of roles to enable resources, services, and innovation.\r\n\r\nIn 2019, a survey of the facility staff at SciLifeLab, a large national research infrastructure in Sweden, led to a recommendation for universities to develop career paths for their staff scientists. Five years later, we have conducted a survey and workshop to determine current views of infrastructure staff on career path diversity in Sweden.\r\n\r\nOur results indicate there is a strong need for clarity and communication about planning and implementation of career path structures at Swedish universities, as well as opportunities to foster excellence in infrastructure staff. While the workshop participants ranked Sweden as a stable and attractive place to work and reported continuous development of their technical and service skills, the lack of recognition of this expertise presents a barrier to a sustainable career.\r\n\r\nWe conclude that there is a need to continue advocating for increased clarity and diversity in career paths for staff scientists in Sweden, and raise the views presented by infrastructure staff on the challenges and opportunities unique to their roles.", "doi": "10.12688/f1000research.164794.1", "pmid": "40904623", "labels": {"Integrated Microscopy Technologies Gothenburg": "Technology development"}, "xrefs": [{"db": "pmc", "key": "PMC12402762"}], "notes": [], "created": "2025-11-05T14:09:53.317Z", "modified": "2025-11-05T14:10:39.124Z"}, {"entity": "publication", "iuid": "6e95ba5c190e4167a9c6aaa5aaea5a48", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6e95ba5c190e4167a9c6aaa5aaea5a48.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6e95ba5c190e4167a9c6aaa5aaea5a48"}}, "title": "Semaglutide effects on energy balance are mediated by Adcyap1+ neurons in the dorsal vagal complex.", "authors": [{"family": "Teixidor-Deulofeu", "given": "J\u00falia", "initials": "J"}, {"family": "Blid Sk\u00f6ldheden", "given": "Sebastian", "initials": "S"}, {"family": "Font-Giron\u00e8s", "given": "Ferran", "initials": "F"}, {"family": "Feje\u0161", "given": "Andrej", "initials": "A"}, {"family": "Ruud", "given": "Johan", "initials": "J"}, {"family": "Engstr\u00f6m Ruud", "given": "Linda", "initials": "L"}], "type": "journal article", "published": "2025-07-01", "journal": {"title": "Cell Metab.", "issn": "1932-7420", "volume": "37", "issue": "7", "pages": "1530-1546.e6", "issn-l": "1550-4131"}, "abstract": "The use of the GLP-1R agonist semaglutide is revolutionizing the treatment of obesity, yet its mechanistic effects on energy balance remain elusive. Here, we demonstrate that reactivation of semaglutide-responsive dorsal vagal complex neurons mimics the drug's effects of reducing food intake and body weight and promoting fat utilization and conditioned taste aversion. We observe that many of the semaglutide-activated area postrema (AP) and nucleus of the solitary tract (NTS) neurons express Adcyap1 mRNA, and ablation of AP/NTS Adcyap1+ neurons largely reverses semaglutide's effects on energy balance acutely in lean mice and in subchronically treated obese mice. Semaglutide-activated AP/NTS Adcyap1+ neurons promote the loss of fat rather than lean mass, with only a modest effect on conditioned taste aversion. Furthermore, NTS Adcyap1+ neurons are engaged by GLP-1R-expressing AP neurons and are necessary for semaglutide-induced activation of several downstream satiety-related structures. Selective targeting of semaglutide-responsive Adcyap1+ neurons holds potential for improved future anti-obesity treatments.", "doi": "10.1016/j.cmet.2025.04.018", "pmid": "40409256", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S1550-4131(25)00256-6"}], "notes": [], "created": "2025-11-05T14:09:55.539Z", "modified": "2025-11-05T14:09:55.543Z"}, {"entity": "publication", "iuid": "e0be7d4528ff466fb50acb46d72fb250", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e0be7d4528ff466fb50acb46d72fb250.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e0be7d4528ff466fb50acb46d72fb250"}}, "title": "STING Agonist Drug Delivery by Bacterial Extracellular Vesicles Induces Synergistic Immuno-Oncology Responses and Efficient Inhibition of Tumour Growth.", "authors": [{"family": "L\u00f6tvall", "given": "Jan", "initials": "J"}, {"family": "Ordouzadeh", "given": "Negar", "initials": "N"}, {"family": "Crescitelli", "given": "Rossella", "initials": "R", "orcid": "0000-0002-1714-3169", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d4b955f26ca4a679deb090e30d0ccf1.json"}}, {"family": "Deshmukh", "given": "Meghshree", "initials": "M"}, {"family": "Jin", "given": "Tao", "initials": "T"}, {"family": "Park", "given": "Kyong-Su", "initials": "KS", "orcid": "0000-0003-0902-7800", "researcher": {"href": "https://publications.scilifelab.se/researcher/26e308b29fe144b49f4db27f4b819c18.json"}}], "type": "journal article", "published": "2025-07-00", "journal": {"title": "J Extracell Vesicles", "issn": "2001-3078", "volume": "14", "issue": "7", "pages": "e70117", "issn-l": "2001-3078"}, "abstract": "Bacterial extracellular vesicles are spherical, nanosized structures with lipid bilayer membranes and can suppress tumour growth in cancer models. However, the efficacy of some of these models is limited. One potential way to enhance their effects is by loading the bacterial vesicles with immunostimulatory molecules. We have here utilised synthetic bacterial vesicles (SyBV), previously shown to have anti-tumour effects but with reduced side effects. We hypothesized that loading SyBV with a STimulator of InterferoN Genes (STING) agonist can enhance anti-tumour effects. SyBV were generated from Escherichia coli membranes through cell breakdown induced by lysozyme and ionic stress. The produced nanovesicles encapsulated the STING agonist (SyBVSTING). SyBVSTING synergistically activated dendritic cells, leading to enhanced production of Interferon-\u03b2. Furthermore, in vivo experiments showed that immunisation with SyBVSTING synergistically suppresses melanoma and colon cancer growth by increasing the tumour infiltration of T cells. Intratumoural or subcutaneous injection of the SyBV resulted in retention in the tumour tissue over 24 h, but with some distribution to local lymph nodes. A toxicology experiment resulted in no histopathological concerns with SyBVSTING. These findings show that SyBV loaded with a STING agonist synergistically enhance anti-tumour immunity and may be a promising clinical immuno-oncology tool.", "doi": "10.1002/jev2.70117", "pmid": "40620049", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12230345"}], "notes": [], "created": "2025-11-05T13:54:01.033Z", "modified": "2025-11-05T13:54:01.099Z"}, {"entity": "publication", "iuid": "74bc759fdf384e7095a0514342639673", "links": {"self": {"href": "https://publications.scilifelab.se/publication/74bc759fdf384e7095a0514342639673.json"}, "display": {"href": "https://publications.scilifelab.se/publication/74bc759fdf384e7095a0514342639673"}}, "title": "Genome-Wide Adaptation to a Complex Environmental Gradient in a Keystone Phytoplankton Species.", "authors": [{"family": "Pinseel", "given": "Eveline", "initials": "E", "orcid": "0000-0002-1801-2187", "researcher": {"href": "https://publications.scilifelab.se/researcher/9abc32586e93470797e0b832287d5d8d.json"}}, {"family": "Ruck", "given": "Elizabeth C", "initials": "EC"}, {"family": "Nakov", "given": "Teofil", "initials": "T"}, {"family": "Jonsson", "given": "Per R", "initials": "PR"}, {"family": "Kourtchenko", "given": "Olga", "initials": "O"}, {"family": "Kremp", "given": "Anke", "initials": "A"}, {"family": "Pinder", "given": "Matthew I M", "initials": "MIM", "orcid": "0000-0003-4407-0214", "researcher": {"href": "https://publications.scilifelab.se/researcher/ca6d9f52178249f3995c3d276fbc2728.json"}}, {"family": "Roberts", "given": "Wade R", "initials": "WR"}, {"family": "Sj\u00f6qvist", "given": "Conny", "initials": "C"}, {"family": "T\u00f6pel", "given": "Mats", "initials": "M", "orcid": "0000-0001-7989-696X", "researcher": {"href": "https://publications.scilifelab.se/researcher/278d2a953da240aa8dd58062eb8f8ff3.json"}}, {"family": "Godhe", "given": "Anna", "initials": "A"}, {"family": "Hahn", "given": "Matthew W", "initials": "MW"}, {"family": "Alverson", "given": "Andrew J", "initials": "AJ", "orcid": "0000-0003-1241-2654", "researcher": {"href": "https://publications.scilifelab.se/researcher/9cfcd9fbf6d349d9b9a26579b6c112c3.json"}}], "type": "journal article", "published": "2025-07-00", "journal": {"title": "Mol. Ecol.", "issn": "1365-294X", "volume": "34", "issue": "13", "pages": "e17817", "issn-l": "0962-1083"}, "abstract": "Marine phytoplankton play essential roles in global primary production and biogeochemical cycles. Yet, the evolutionary genetic underpinnings of phytoplankton adaptation to complex marine and coastal environments, where many environmental variables fluctuate and interact, remain unclear. We combined population genomics with experimental transcriptomics to investigate the genomic basis underlying a natural evolutionary experiment that has played out over the past 8000 years in one of the world's largest brackish water bodies: the colonisation of the Baltic Sea by the ancestrally marine diatom Skeletonema marinoi. To this end, we combined target capture of the entire nuclear genome with pooled shotgun sequencing, and showed that the method performs well on both cultures and single cells. Genotype-environment association analyses identified > 1000 genes with signals of selection in response to major environmental gradients in the Baltic Sea, which apart from salinity, include marked differences in temperature and nutrient supply. Locally adapted genes were related to diverse metabolic processes, including signal transduction, cell cycle, DNA methylation and maintenance of homeostasis. The locally adapted genes showed significant overlap with salinity-responsive genes identified in a laboratory common garden experiment, suggesting the Baltic salinity gradient contributes to local adaptation of S. marinoi. Taken together, our data show that local adaptation of phytoplankton to complex coastal environments, which are characterised by a multitude of environmental gradients, is driven by widespread changes in diverse metabolic pathways and functions.", "doi": "10.1111/mec.17817", "pmid": "40491268", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12186713"}], "notes": [], "created": "2025-11-05T13:58:54.365Z", "modified": "2025-11-05T13:58:54.571Z"}, {"entity": "publication", "iuid": "081d42ccc86240e9ba5bc5a2b40a7eec", "links": {"self": {"href": "https://publications.scilifelab.se/publication/081d42ccc86240e9ba5bc5a2b40a7eec.json"}, "display": {"href": "https://publications.scilifelab.se/publication/081d42ccc86240e9ba5bc5a2b40a7eec"}}, "title": "Real-time genome imaging of host interactions in adeno-associated virus genome release.", "authors": [{"family": "Bustamante-Jaramillo", "given": "Luisa F", "initials": "LF"}, {"family": "Yue", "given": "Lei", "initials": "L"}, {"family": "Fingal", "given": "Joshua", "initials": "J"}, {"family": "Rydell", "given": "Gustaf", "initials": "G"}, {"family": "Johansson", "given": "Maria", "initials": "M"}, {"family": "Edreira", "given": "Tomas", "initials": "T"}, {"family": "M\u00fcller", "given": "Oliver J", "initials": "OJ"}, {"family": "Hille", "given": "Susanne", "initials": "S"}, {"family": "M\u00fcller", "given": "Martin", "initials": "M"}, {"family": "Gallardo", "given": "Franck", "initials": "F"}, {"family": "Chen", "given": "Qingxin", "initials": "Q"}, {"family": "Blondot", "given": "Marie-Lise", "initials": "ML"}, {"family": "Kann", "given": "Michael", "initials": "M"}], "type": "journal article", "published": "2025-06-20", "journal": {"title": "iScience", "issn": "2589-0042", "volume": "28", "issue": "6", "pages": "112624", "issn-l": "2589-0042"}, "abstract": "Adeno-associated virus (AAVs) with a self-complementary genome (sc) comprising a gene of interest are used in gene therapy. Their efficiency is limited but the molecular factors contributing to this restriction are poorly understood. We utilized scAAV2 containing a fluorescent protein-binding anchor sequence on its genome allowing visualization of released genomes by time-lapse microscopy. Pairing this technique with capsid staining, we showed that scAAV2 genome release was initiated by a partial genome exposure, triggered by elevated calcium levels while the capsids interacted with proteins of the nuclear pore. Genome release occurred subsequently requiring Rad52 decamerization in the vicinity of the host chromatin. A fraction of the released genomes was degraded by Mre11, an essential factor for chromatin stability, and cellular DNA double-strand breaks. These steps were key-factors limiting transduction, suggesting that temporary modulation of DNA damage-response-proteins is a promising way to increase scAAV efficiency in therapy.", "doi": "10.1016/j.isci.2025.112624", "pmid": "40546945", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12178803"}, {"db": "pii", "key": "S2589-0042(25)00885-5"}], "notes": [], "created": "2025-11-05T13:48:04.799Z", "modified": "2025-11-05T13:48:04.808Z"}, {"entity": "publication", "iuid": "c466edad3243407ba07ae58843066301", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c466edad3243407ba07ae58843066301.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c466edad3243407ba07ae58843066301"}}, "title": "Small molecules restore mutant mitochondrial DNA polymerase activity.", "authors": [{"family": "Valenzuela", "given": "Sebastian", "initials": "S", "orcid": "0000-0001-5153-8431", "researcher": {"href": "https://publications.scilifelab.se/researcher/16c5cd1a4e8a4d9389514f33049240a5.json"}}, {"family": "Zhu", "given": "Xuefeng", "initials": "X"}, {"family": "Macao", "given": "Bertil", "initials": "B"}, {"family": "Stamgren", "given": "Mattias", "initials": "M"}, {"family": "Geukens", "given": "Carol", "initials": "C"}, {"family": "Charifson", "given": "Paul S", "initials": "PS"}, {"family": "Kern", "given": "Gunther", "initials": "G"}, {"family": "Hoberg", "given": "Emily", "initials": "E"}, {"family": "Jenninger", "given": "Louise", "initials": "L"}, {"family": "Gruszczyk", "given": "Anja V", "initials": "AV", "orcid": "0000-0003-3060-4107", "researcher": {"href": "https://publications.scilifelab.se/researcher/57299dfd50ed45219e6d9f9765f6cd12.json"}}, {"family": "Lee", "given": "Seoeun", "initials": "S"}, {"family": "Johansson", "given": "Katarina A S", "initials": "KAS", "orcid": "0009-0005-8992-7631", "researcher": {"href": "https://publications.scilifelab.se/researcher/d3bac3ed243c4f0493e0d494f79a7ca2.json"}}, {"family": "Miralles Fust\u00e9", "given": "Javier", "initials": "J", "orcid": "0000-0001-8818-9650", "researcher": {"href": "https://publications.scilifelab.se/researcher/2dcf35ce5b204221b2167f281ce219b3.json"}}, {"family": "Shi", "given": "Yonghong", "initials": "Y"}, {"family": "Kerns", "given": "S Jordan", "initials": "SJ"}, {"family": "Arabanian", "given": "Laleh", "initials": "L"}, {"family": "Martinez Botella", "given": "Gabriel", "initials": "G"}, {"family": "Ekstr\u00f6m", "given": "Sofie", "initials": "S"}, {"family": "Green", "given": "Jeremy", "initials": "J", "orcid": "0000-0003-4544-6412", "researcher": {"href": "https://publications.scilifelab.se/researcher/91088e7b066944c7b415aa1b18632c44.json"}}, {"family": "Griffin", "given": "Andrew M", "initials": "AM"}, {"family": "Pardo-Hern\u00e1ndez", "given": "Carlos", "initials": "C"}, {"family": "Keating", "given": "Thomas A", "initials": "TA", "orcid": "0009-0009-1386-2471", "researcher": {"href": "https://publications.scilifelab.se/researcher/52c4d61c63fe4129b9d06c0758c6cef9.json"}}, {"family": "K\u00fcppers-Munther", "given": "Barbara", "initials": "B"}, {"family": "Larsson", "given": "Nils-G\u00f6ran", "initials": "NG", "orcid": "0000-0001-5100-996X", "researcher": {"href": "https://publications.scilifelab.se/researcher/1dc68aa2893a4ab8845fc32d8d6bc59a.json"}}, {"family": "Phan", "given": "Cindy", "initials": "C"}, {"family": "Posse", "given": "Viktor", "initials": "V", "orcid": "0000-0003-4936-4967", "researcher": {"href": "https://publications.scilifelab.se/researcher/2bd6a8d4e0f94ea090d12a376b17876a.json"}}, {"family": "Jones", "given": "Juli E", "initials": "JE"}, {"family": "Xie", "given": "Xie", "initials": "X"}, {"family": "Giroux", "given": "Simon", "initials": "S", "orcid": "0000-0003-1499-2576", "researcher": {"href": "https://publications.scilifelab.se/researcher/7dbcb75a94a24eff8dd3737366bb3423.json"}}, {"family": "Gustafsson", "given": "Claes M", "initials": "CM", "orcid": "0000-0003-3531-8468", "researcher": {"href": "https://publications.scilifelab.se/researcher/2851656430d147dab7a8a32e50fee7b7.json"}}, {"family": "Falkenberg", "given": "Maria", "initials": "M", "orcid": "0000-0001-8713-173X", "researcher": {"href": "https://publications.scilifelab.se/researcher/562109b99a5c4eb3bd8b92f30014828b.json"}}], "type": "journal article", "published": "2025-06-00", "journal": {"title": "Nature", "issn": "1476-4687", "volume": "642", "issue": "8067", "pages": "501-507", "issn-l": "0028-0836"}, "abstract": "Mammalian mitochondrial DNA (mtDNA) is replicated by DNA polymerase \u03b3 (POL\u03b3), a heterotrimeric complex consisting of a catalytic POL\u03b3A subunit and two accessory POL\u03b3B subunits1. More than 300 mutations in POLG, the gene encoding the catalytic subunit, have been linked to severe, progressive conditions with high rates of morbidity and mortality, for which no treatment exists2. Here we report on the discovery and characterization of PZL-A, a first-in-class small-molecule activator of mtDNA synthesis that is capable of restoring function to the most common mutant variants of POL\u03b3. PZL-A binds to an allosteric site at the interface between the catalytic POL\u03b3A subunit and the proximal POL\u03b3B subunit, a region that is unaffected by nearly all disease-causing mutations. The compound restores wild-type-like activity to mutant forms of POL\u03b3 in vitro and activates mtDNA synthesis in cells from paediatric patients with lethal POLG disease, thereby enhancing biogenesis of the oxidative phosphorylation machinery and cellular respiration. Our work demonstrates that a small molecule can restore function to mutant DNA polymerases, offering a promising avenue for treating POLG disorders and other severe conditions linked to depletion of mtDNA.", "doi": "10.1038/s41586-025-08856-9", "pmid": "40205042", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service", "Cryo-EM": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12158775"}, {"db": "pii", "key": "10.1038/s41586-025-08856-9"}], "notes": [], "created": "2025-11-05T14:10:00.381Z", "modified": "2025-11-13T12:50:07.085Z"}, {"entity": "publication", "iuid": "499254acb4eb4139bf11f17fd8968652", "links": {"self": {"href": "https://publications.scilifelab.se/publication/499254acb4eb4139bf11f17fd8968652.json"}, "display": {"href": "https://publications.scilifelab.se/publication/499254acb4eb4139bf11f17fd8968652"}}, "title": "Modelling POLG mutations in mice unravels a critical role of POL\u03b3\u0392 in regulating phenotypic severity.", "authors": [{"family": "Corr\u00e0", "given": "Samantha", "initials": "S"}, {"family": "Zuppardo", "given": "Alessandro", "initials": "A", "orcid": "0000-0001-9601-3567", "researcher": {"href": "https://publications.scilifelab.se/researcher/308877ae9bac46328666ca4e56b73d26.json"}}, {"family": "Valenzuela", "given": "Sebastian", "initials": "S", "orcid": "0000-0001-5153-8431", "researcher": {"href": "https://publications.scilifelab.se/researcher/16c5cd1a4e8a4d9389514f33049240a5.json"}}, {"family": "Jenninger", "given": "Louise", "initials": "L"}, {"family": "Cerutti", "given": "Raffaele", "initials": "R"}, {"family": "Sillamaa", "given": "Sirelin", "initials": "S", "orcid": "0000-0001-8077-9963", "researcher": {"href": "https://publications.scilifelab.se/researcher/29a3fbab3f684386a2e08236bfd8674e.json"}}, {"family": "Hoberg", "given": "Emily", "initials": "E"}, {"family": "Johansson", "given": "Katarina A S", "initials": "KAS", "orcid": "0009-0005-8992-7631", "researcher": {"href": "https://publications.scilifelab.se/researcher/d3bac3ed243c4f0493e0d494f79a7ca2.json"}}, {"family": "Rovsnik", "given": "Urska", "initials": "U"}, {"family": "Volta", "given": "Sara", "initials": "S"}, {"family": "Silva-Pinheiro", "given": "Pedro", "initials": "P", "orcid": "0000-0002-0872-5749", "researcher": {"href": "https://publications.scilifelab.se/researcher/bbc93779b0704e55a91eb4d755255aed.json"}}, {"family": "Davis", "given": "Hannah", "initials": "H"}, {"family": "Trifunovic", "given": "Aleksandra", "initials": "A", "orcid": "0000-0002-5472-3517", "researcher": {"href": "https://publications.scilifelab.se/researcher/bf7d2fa56e714134bc66ca5884b8e86b.json"}}, {"family": "Minczuk", "given": "Michal", "initials": "M", "orcid": "0000-0001-8242-1420", "researcher": {"href": "https://publications.scilifelab.se/researcher/8f03f6f8725149c6938067d043ca4f7f.json"}}, {"family": "Gustafsson", "given": "Claes M", "initials": "CM", "orcid": "0000-0003-3531-8468", "researcher": {"href": "https://publications.scilifelab.se/researcher/2851656430d147dab7a8a32e50fee7b7.json"}}, {"family": "Suomalainen", "given": "Anu", "initials": "A", "orcid": "0000-0003-4833-5195", "researcher": {"href": "https://publications.scilifelab.se/researcher/6625705a6d4246c3a5f397008173899f.json"}}, {"family": "Zeviani", "given": "Massimo", "initials": "M"}, {"family": "Macao", "given": "Bertil", "initials": "B", "orcid": "0000-0001-6511-6125", "researcher": {"href": "https://publications.scilifelab.se/researcher/b5445196c3234bdb8686e85f77a66f3f.json"}}, {"family": "Zhu", "given": "Xuefeng", "initials": "X", "orcid": "0000-0002-4759-4446", "researcher": {"href": "https://publications.scilifelab.se/researcher/eebd5f32ac0c48869c90ba2d2ba94fa9.json"}}, {"family": "Falkenberg", "given": "Maria", "initials": "M", "orcid": "0000-0001-8713-173X", "researcher": {"href": "https://publications.scilifelab.se/researcher/562109b99a5c4eb3bd8b92f30014828b.json"}}, {"family": "Viscomi", "given": "Carlo", "initials": "C", "orcid": "0000-0001-6050-0566", "researcher": {"href": "https://publications.scilifelab.se/researcher/e84ba370ae594e6db85d338ab69a02df.json"}}], "type": "journal article", "published": "2025-05-23", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "16", "issue": "1", "pages": "4782", "issn-l": "2041-1723"}, "abstract": "DNA polymerase \u03b3 (POL\u03b3), responsible for mitochondrial DNA replication, consists of a catalytic POL\u03b3A subunit and two accessory POL\u03b3B subunits. Mutations in POLG, which encodes POL\u03b3A, lead to various mitochondrial diseases. We investigated the most common POLG mutations (A467T, W748S, G848S, Y955C) by characterizing human and mouse POL\u03b3 variants. Our data reveal that these mutations significantly impair POL\u03b3 activities, with mouse variants exhibiting milder defects. Cryogenic electron microscopy highlighted structural differences between human and mouse POL\u03b3, particularly in the POL\u03b3B subunit, which may explain the higher activity of mouse POL\u03b3 and the reduced severity of mutations in mice. We further generated a panel of mouse models mirroring common human POLG mutations, providing crucial insights into the pathogenesis of POLG-related disorders and establishing robust models for therapeutic development. Our findings emphasize the importance of POL\u03b3B in modulating the severity of POLG mutations.", "doi": "10.1038/s41467-025-60059-y", "pmid": "40404629", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service", "Cryo-EM": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12098916"}, {"db": "pii", "key": "10.1038/s41467-025-60059-y"}], "notes": [], "created": "2025-11-05T13:48:13.014Z", "modified": "2025-11-13T12:47:34.901Z"}, {"entity": "publication", "iuid": "da040e812a93400d8e2d085b287e2d33", "links": {"self": {"href": "https://publications.scilifelab.se/publication/da040e812a93400d8e2d085b287e2d33.json"}, "display": {"href": "https://publications.scilifelab.se/publication/da040e812a93400d8e2d085b287e2d33"}}, "title": "Characterization of Extracellular Vesicles Derived From Human Precision-Cut Liver Slices in Metabolic Dysfunction-Associated Steatotic Liver Disease.", "authors": [{"family": "Geng", "given": "Yana", "initials": "Y", "orcid": "0000-0003-1529-0875", "researcher": {"href": "https://publications.scilifelab.se/researcher/bd1524719c71429bba79b708066b5874.json"}}, {"family": "Luo", "given": "Ke", "initials": "K"}, {"family": "Stam", "given": "Janine", "initials": "J"}, {"family": "Oosterhuis", "given": "Dorenda", "initials": "D"}, {"family": "Gorter", "given": "Alan R", "initials": "AR"}, {"family": "van den Heuvel", "given": "Marius", "initials": "M"}, {"family": "Crescitelli", "given": "Rossella", "initials": "R", "orcid": "0000-0002-1714-3169", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d4b955f26ca4a679deb090e30d0ccf1.json"}}, {"family": "de Meijer", "given": "Vincent E", "initials": "VE"}, {"family": "Wolters", "given": "Justina C", "initials": "JC"}, {"family": "Olinga", "given": "Peter", "initials": "P"}], "type": "journal article", "published": "2025-05-00", "journal": {"title": "J Extracell Biol", "issn": "2768-2811", "volume": "4", "issue": "5", "pages": "e70043", "issn-l": null}, "abstract": "Extracellular vesicles (EVs) are cell-produced, membrane-surrounded vesicles that harbour the biological features of donor cells. In the current study, we are the first to isolate and characterize EVs isolated from human precision-cut liver slices (PCLS), obtained from both healthy and metabolic dysfunction-associated steatohepatitis (MASH) cirrhotic livers. PCLS derived from patients can faithfully represent disease conditions in humans. EVs were isolated from human PCLS after incubating in normal medium or modified medium that mimics the pathophysiological environment of metabolic dysfunction associated liver disease (MASLD). MASH PCLS produced higher amounts of EVs compared to healthy PCLS (p < 0.001). Mass spectrometry revealed that around 300 proteins were significantly different in EVs derived from MASH PCLS versus healthy PCLS (FDR < 0.05), irrespective of the type of medium. Significantly changed EV proteins were largely involved in signalling receptor binding function and showed potential in promoting fibrosis. In the liver, these ligand-associated receptors are highly expressed in hepatic stellate cells, and the MASH EVs functionally promoted the activation of hepatic stellate cells. Furthermore, the amounts of EpCAM and ITGA3 in EVs were positively associated with the progression of MASLD, which suggests the use of liver-derived EVs as potential biomarkers for MASLD. Characterization of EVs derived from human PCLS may assist future studies in investigating the pathogenesis and identifying liver-specific EVs as biomarkers of MASLD.", "doi": "10.1002/jex2.70043", "pmid": "40313415", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12042696"}, {"db": "pii", "key": "JEX270043"}], "notes": [], "created": "2025-11-05T13:50:42.948Z", "modified": "2025-11-05T13:50:43.051Z"}, {"entity": "publication", "iuid": "84bb39aa7a504a65be8100a8fd9d1a79", "links": {"self": {"href": "https://publications.scilifelab.se/publication/84bb39aa7a504a65be8100a8fd9d1a79.json"}, "display": {"href": "https://publications.scilifelab.se/publication/84bb39aa7a504a65be8100a8fd9d1a79"}}, "title": "Amino acid restriction sensitizes lung cancer cells to ferroptosis via GCN2-dependent activation of the integrated stress response", "authors": [{"family": "Garellick", "given": "Viktor J", "initials": "VJ"}, {"family": "Gul", "given": "Nadia", "initials": "N"}, {"family": "Horrieh", "given": "Parvin", "initials": "P"}, {"family": "Mustafa", "given": "Dyar", "initials": "D"}, {"family": "Patel", "given": "Angana A H", "initials": "AAH"}, {"family": "Dankis", "given": "Martin", "initials": "M"}, {"family": "Alvarez", "given": "Samantha", "initials": "S"}, {"family": "Berndtson", "given": "Johanna", "initials": "J"}, {"family": "Schwartz", "given": "Maria", "initials": "M"}, {"family": "Persson", "given": "Andreas", "initials": "A", "orcid": "0000-0001-8427-0232", "researcher": {"href": "https://publications.scilifelab.se/researcher/c2a654d9571c4faeac9cd4294e67958d.json"}}, {"family": "Zahirovic", "given": "Fikret", "initials": "F"}, {"family": "Wiel", "given": "Clotilde", "initials": "C"}, {"family": "Sayin", "given": "Volkan I", "initials": "VI"}, {"family": "Lindahl", "given": "Per", "initials": "P"}], "type": "posted-content", "published": "2025-04-16", "journal": {"title": "biorxiv", "issn": null, "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": null, "doi": "10.1101/2025.04.10.648120", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2025-11-05T13:50:40.411Z", "modified": "2025-12-18T19:16:46.266Z"}, {"entity": "publication", "iuid": "bb84c8f0da2546d197d9be264a758437", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bb84c8f0da2546d197d9be264a758437.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bb84c8f0da2546d197d9be264a758437"}}, "title": "Design and application of a fluorescent probe for imaging of endogenous Bruton's tyrosine kinase with preserved enzymatic activity.", "authors": [{"family": "Valaka", "given": "Anna P", "initials": "AP", "orcid": "0009-0008-7007-6971", "researcher": {"href": "https://publications.scilifelab.se/researcher/90c945c6f7b84acc8fc0097ec194332e.json"}}, {"family": "Nystr\u00f6m", "given": "Hampus", "initials": "H", "orcid": "0009-0006-8139-3839", "researcher": {"href": "https://publications.scilifelab.se/researcher/a763c1525ea446bd913291a2599ea9f7.json"}}, {"family": "H\u00e5versen", "given": "Liliana", "initials": "L"}, {"family": "Benitez-Martin", "given": "Carlos", "initials": "C", "orcid": "0000-0003-1821-9388", "researcher": {"href": "https://publications.scilifelab.se/researcher/d1fcdd6e053b462998fe7f463be60d96.json"}}, {"family": "Sch\u00e4fer", "given": "Clara", "initials": "C", "orcid": "0000-0001-7634-3980", "researcher": {"href": "https://publications.scilifelab.se/researcher/58fcf0b78e574d5f9a52fcab14632117.json"}}, {"family": "Jang", "given": "Woo Suk", "initials": "WS"}, {"family": "Camponeschi", "given": "Alessandro", "initials": "A", "orcid": "0000-0002-6472-2438", "researcher": {"href": "https://publications.scilifelab.se/researcher/ccbaffafd6a24f4abed1e402219fa472.json"}}, {"family": "Andr\u00e9asson", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4695-7943", "researcher": {"href": "https://publications.scilifelab.se/researcher/28eb5affb5664c54be9171dfce6bea15.json"}}, {"family": "Bor\u00e9n", "given": "Jan", "initials": "J", "orcid": "0000-0003-0786-8091", "researcher": {"href": "https://publications.scilifelab.se/researcher/1e85f6d287ce4c60a7b35b287efb4f79.json"}}, {"family": "Gr\u00f8tli", "given": "Morten", "initials": "M", "orcid": "0000-0003-3621-4222", "researcher": {"href": "https://publications.scilifelab.se/researcher/764706606bcb4afba1150af332c0f124.json"}}], "type": "journal article", "published": "2025-04-02", "journal": {"title": "RSC Chem Biol", "issn": "2633-0679", "issn-l": null, "volume": "6", "issue": "4", "pages": "618-629"}, "abstract": "Fluorophore integration into proteins within living cells is essential for exploring proteins in their natural environment. Bruton's tyrosine kinase (BTK), is a validated oncology target and is crucial for B cell proliferation and activation. Developing BTK-labelling probes is key to understand BTK's dynamic signalling pathway. In this work, we aimed to develop a novel fluorescent labelling probe for endogenous BTK imaging while preserving its enzymatic activity. Evobrutinib, a second-generation BTK inhibitor with high selectivity, was chosen as the scaffold. We designed two probes, Evo-1 and Evo-2, with a BODIPY fluorescent group, guided by molecular modelling. The synthesis was achieved using optimised Suzuki-Miyaura cross-coupling and amide coupling reactions. Biochemical assays confirmed covalent binding to Cys481 of BTK while preserving its enzymatic activity. Labelling of endogenous BTK with Evo-2 with reduced off-target effects in Ramos cells was validated in cellular assays. The dynamic signalling pathway of BTK in its native environment was investigated by confocal microscopy with Evo-2. This methodology is a valuable asset in the chemical biology toolbox for studying protein dynamics and interactions in real time without interfering with the protein activity.", "doi": "10.1039/d4cb00313f", "pmid": "40026844", "labels": {"Glycoproteomics and MS Proteomics": "Service", "Integrated Microscopy Technologies Gothenburg": "Service", "Swedish NMR Centre": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11867108"}, {"db": "pii", "key": "d4cb00313f"}], "notes": [], "created": "2025-10-23T16:03:12.593Z", "modified": "2025-11-27T13:34:09.343Z"}, {"entity": "publication", "iuid": "eed9d79d809f4d5d864e6170b1dcfc20", "links": {"self": {"href": "https://publications.scilifelab.se/publication/eed9d79d809f4d5d864e6170b1dcfc20.json"}, "display": {"href": "https://publications.scilifelab.se/publication/eed9d79d809f4d5d864e6170b1dcfc20"}}, "title": "Titanium micro-particles are commonly found in soft tissues surrounding dental implants.", "authors": [{"family": "Dionigi", "given": "Carlotta", "initials": "C", "orcid": "0000-0002-4195-0729", "researcher": {"href": "https://publications.scilifelab.se/researcher/5ee57750bddd48a3a323e397c64ba435.json"}}, {"family": "Nagy", "given": "Gyula", "initials": "G", "orcid": "0000-0003-3172-5736", "researcher": {"href": "https://publications.scilifelab.se/researcher/07c27d64291549dca9eda3709cbab30d.json"}}, {"family": "Derks", "given": "Jan", "initials": "J"}, {"family": "Ichioka", "given": "Yuki", "initials": "Y"}, {"family": "Tomasi", "given": "Cristiano", "initials": "C", "orcid": "0000-0002-3610-6574", "researcher": {"href": "https://publications.scilifelab.se/researcher/a3067facfa6743db83d011e510fcddcf.json"}}, {"family": "Larsson", "given": "Lena", "initials": "L"}, {"family": "Primetzhofer", "given": "Daniel", "initials": "D", "orcid": "0000-0002-5815-3742", "researcher": {"href": "https://publications.scilifelab.se/researcher/eeed8e1ab76842eab7f052f57abcd960.json"}}, {"family": "Berglundh", "given": "Tord", "initials": "T", "orcid": "0000-0001-5864-6398", "researcher": {"href": "https://publications.scilifelab.se/researcher/2d29bd79b2914b47b00a0c1005b30b43.json"}}], "type": "journal article", "published": "2025-03-18", "journal": {"title": "Commun Med (Lond)", "issn": "2730-664X", "volume": "5", "issue": "1", "pages": "78", "issn-l": null}, "abstract": "Dental implants are one of the most frequently used medical devices for therapeutic purposes in dentistry. Peri-implantitis is a severe, microbial biofilm-associated condition, characterized by inflammation in peri-implant soft tissues and destruction of supporting bone. It has been suggested that metal particles originating from the implant may influence the local host response to microbial biofilms.\n\nSoft tissue biopsies were collected from implant sites with and without peri-implantitis in 21 patients. Micro Proton-induced X-ray Emission (\u00b5-PIXE) analysis was used to localize, quantify and characterize titanium micro-particles within tissues. RNA sequencing was performed to evaluate potential associations between titanium micro-particles and gene expression profiles in peri-implantitis lesions.\n\nTitanium micro-particles are consistent findings in soft tissues surrounding dental implants. Their occurrence varies across patients but not between sites with and without peri-implantitis within the same individual. Most particles reside in a 2-mm wide tissue portion close to the implant/tissue interface. The time in function of the implants does not influence the volumetric density of titanium micro-particles, while implant systems do. Fourteen differentially expressed genes are identified when comparing peri-implantitis samples with high and low densities of titanium micro-particles. The gene-set enrichment analysis reveals functions related to the regulation of the immune response and epithelial development.\n\nThe present results indicate that titanium micro-particles are commonly found in tissues surrounding dental implants and are not associated with the occurrence of peri-implantitis.", "doi": "10.1038/s43856-025-00756-3", "pmid": "40102654", "labels": {"Clinical Genomics": "Service", "Clinical Genomics Gothenburg": "Service", "Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11920262"}, {"db": "pii", "key": "10.1038/s43856-025-00756-3"}], "notes": [], "created": "2025-07-08T13:53:22.922Z", "modified": "2025-11-05T13:50:37.870Z"}, {"entity": "publication", "iuid": "c130f0ff51454fccb12fbb55363f71e4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c130f0ff51454fccb12fbb55363f71e4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c130f0ff51454fccb12fbb55363f71e4"}}, "title": "Therapeutic Potential of STE20-Type Kinase STK25 Inhibition for the Prevention and Treatment of Metabolically Induced Hepatocellular Carcinoma.", "authors": [{"family": "Xia", "given": "Ying", "initials": "Y"}, {"family": "Caputo", "given": "Mara", "initials": "M"}, {"family": "Andersson", "given": "Emma", "initials": "E"}, {"family": "Asiedu", "given": "Bernice", "initials": "B"}, {"family": "Zhang", "given": "Jingjing", "initials": "J"}, {"family": "Hou", "given": "Wei", "initials": "W"}, {"family": "Amrutkar", "given": "Manoj", "initials": "M"}, {"family": "Cansby", "given": "Emmelie", "initials": "E"}, {"family": "Gul", "given": "Nadia", "initials": "N"}, {"family": "Gemmink", "given": "Anne", "initials": "A"}, {"family": "Myers", "given": "Caitlyn", "initials": "C"}, {"family": "Aghajan", "given": "Mariam", "initials": "M"}, {"family": "Booten", "given": "Sheri", "initials": "S"}, {"family": "Hoy", "given": "Andrew J", "initials": "AJ"}, {"family": "H\u00e4rtlova", "given": "Anetta", "initials": "A"}, {"family": "Lindahl", "given": "Per", "initials": "P"}, {"family": "St\u00e5hlberg", "given": "Anders", "initials": "A"}, {"family": "Schaart", "given": "Gert", "initials": "G"}, {"family": "Hesselink", "given": "Matthijs K C", "initials": "MKC"}, {"family": "Peter", "given": "Andreas", "initials": "A"}, {"family": "Murray", "given": "Sue", "initials": "S"}, {"family": "Mahlapuu", "given": "Margit", "initials": "M"}], "type": "journal article", "published": "2025-02-28", "journal": {"title": "Cellular and Molecular Gastroenterology and Hepatology", "issn": "2352-345X", "volume": "19", "issue": "7", "pages": "101485", "issn-l": "2352-345X"}, "abstract": "Hepatocellular carcinoma (HCC) is a rapidly growing malignancy with high mortality. Recently, metabolic dysfunction-associated steatohepatitis (MASH) has emerged as a major HCC catalyst; however, signals driving transition of MASH to HCC remain elusive and treatment options are limited. Herein, we investigated the role of STE20-type kinase STK25, a critical regulator of hepatocellular lipotoxic milieu and MASH susceptibility, in the initiation and progression of MASH-related HCC.\n\nThe clinical relevance of STK25 in HCC was assessed in publicly available datasets and by RT-qPCR and proximity ligation assay in a validation cohort. The functional significance of STK25 silencing in human hepatoma cells was evaluated in vitro and in a subcutaneous xenograft mouse model. The therapeutic potential of STK25 antagonism was examined in a mouse model of MASH-driven HCC, induced by a single diethylnitrosamine injection combined with a high-fat diet.\n\nAnalysis of public databases and in-house cohorts revealed that STK25 expression in human liver biopsies positively correlated with HCC incidence and severity. The in vitro silencing of STK25 in human hepatoma cells suppressed proliferation, migration, and invasion with efficacy comparable to that achieved by anti-HCC drugs sorafenib or regorafenib. STK25 knockout in human hepatoma cells also blocked tumor formation and growth in a subcutaneous xenograft mouse model. Furthermore, pharmacologic inhibition of STK25 with antisense oligonucleotides-administered systemically or hepatocyte-specifically-efficiently mitigated the development and exacerbation of hepatocarcinogenesis in a mouse model of MASH-driven HCC.\n\nThis study underscores STK25 antagonism as a promising therapeutic strategy for the prevention and treatment of HCC in the context of MASH.", "doi": "10.1016/j.jcmgh.2025.101485", "pmid": "40024534", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12022666"}, {"db": "pii", "key": "S2352-345X(25)00026-8"}], "notes": [], "created": "2025-11-05T13:58:47.588Z", "modified": "2025-11-05T13:58:47.594Z"}, {"entity": "publication", "iuid": "7e61a1bb95354373a3a6f1dd1b5438bb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7e61a1bb95354373a3a6f1dd1b5438bb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7e61a1bb95354373a3a6f1dd1b5438bb"}}, "title": "Characterization and description of Clostridium filamentum ETTB, a novel gut bacterium with TLR5 modulating properties", "authors": [{"family": "Makki", "given": "Kassem", "initials": "K", "orcid": "0000-0002-7488-3411", "researcher": {"href": "https://publications.scilifelab.se/researcher/471da96cf7324c0bb45f8d2fb6b66fbc.json"}}, {"family": "Martino", "given": "Maria Elena", "initials": "ME"}, {"family": "Alberdi", "given": "Antton", "initials": "A"}, {"family": "Aizpurua", "given": "Ostaizka", "initials": "O"}, {"family": "Quagliariello", "given": "Andrea", "initials": "A"}, {"family": "Olsson", "given": "Lisa", "initials": "L"}, {"family": "Clasen", "given": "Sara", "initials": "S"}, {"family": "J\u00f6nsson", "given": "Johanna", "initials": "J"}, {"family": "Brolin", "given": "Harald", "initials": "H"}, {"family": "Dwibedi", "given": "Chinmay", "initials": "C", "orcid": "0000-0001-6416-4440", "researcher": {"href": "https://publications.scilifelab.se/researcher/a0b0dbf807be449da1856c0c018f13a3.json"}}, {"family": "Yang", "given": "Gaohua", "initials": "G"}, {"family": "Favero", "given": "Chiara", "initials": "C"}, {"family": "Bergh", "given": "Per Olof", "initials": "PO"}, {"family": "Schnupf", "given": "Pamela", "initials": "P"}, {"family": "Ley", "given": "Ruth", "initials": "R"}, {"family": "Khan", "given": "Muhammad Tanweer", "initials": "MT"}, {"family": "Tremaroli", "given": "Valentina", "initials": "V", "orcid": "0000-0002-9150-4233", "researcher": {"href": "https://publications.scilifelab.se/researcher/38ddf7701aaf4c01b160f2a1c596dc6f.json"}}, {"family": "B\u00e4ckhed", "given": "Fredrik", "initials": "F", "orcid": "0000-0002-4871-8818", "researcher": {"href": "https://publications.scilifelab.se/researcher/1689878e0c5542d08d3e2d5043a6ce5c.json"}}], "type": "posted-content", "published": "2025-02-28", "journal": {"title": "biorxiv", "issn": null, "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": null, "doi": "10.1101/2025.02.28.640726", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [], "notes": [], "created": "2025-11-05T13:54:11.274Z", "modified": "2025-12-18T19:19:32.052Z"}, {"entity": "publication", "iuid": "82da1c79ab3d480f8ef86647b089b801", "links": {"self": {"href": "https://publications.scilifelab.se/publication/82da1c79ab3d480f8ef86647b089b801.json"}, "display": {"href": "https://publications.scilifelab.se/publication/82da1c79ab3d480f8ef86647b089b801"}}, "title": "Aberrant growth and expansion in Penium margaritaceum triggered by disruption of microtubules and the cell wall.", "authors": [{"family": "LoRicco", "given": "Josephine G", "initials": "JG", "orcid": "0000-0002-1550-2463", "researcher": {"href": "https://publications.scilifelab.se/researcher/edbbb3add76a4370b4037d1aaa8132dc.json"}}, {"family": "Malone", "given": "Stuart", "initials": "S"}, {"family": "Becker", "given": "Abigail", "initials": "A"}, {"family": "Xue", "given": "Nichole", "initials": "N"}, {"family": "Bagdan", "given": "Kaylee", "initials": "K", "orcid": "0000-0002-5060-4270", "researcher": {"href": "https://publications.scilifelab.se/researcher/4f069d44c6094291a5452952b4209e66.json"}}, {"family": "Eastman", "given": "Anika", "initials": "A"}, {"family": "Sgambettera", "given": "Gabriel", "initials": "G"}, {"family": "Winegrad", "given": "Aaron", "initials": "A"}, {"family": "Gibeau", "given": "Benjamin", "initials": "B"}, {"family": "Bauer", "given": "Lindsay", "initials": "L"}, {"family": "Epstein", "given": "Ruby", "initials": "R"}, {"family": "Domozych", "given": "David S", "initials": "DS", "orcid": "0000-0001-8800-0061", "researcher": {"href": "https://publications.scilifelab.se/researcher/389412e319244f48955e4aeeac9ec616.json"}}], "type": "journal article", "published": "2025-02-25", "journal": {"title": "J. Exp. Bot.", "issn": "1460-2431", "volume": "76", "issue": "4", "pages": "961-979", "issn-l": "0022-0957"}, "abstract": "Penium margaritaceum, a unicellular zygnematophyte (Streptophyta), was employed to elucidate changes in cell expansion when cells were challenged with the fungal pectinolytic enzyme, pectate lyase, and/or the microtubule-disrupting agent, amiprophos-methyl (APM). Microtubule disruption by APM resulted in significant swelling at expansion zones. These swollen zones provided an easy marker for the location of expansion zones, particularly in cells with altered cell wall pectin. Short-term treatment with pectate lyase showed pectin degradation primarily at the isthmus expansion zone and two satellite bands, corresponding to the location of future expansion in daughter cells. When the homogalacturonan lattice of the cell wall was removed by treatment with pectate lyase during long treatments, cell division was maintained, but daughter cell products were considerably smaller. Treatment of cells with a mixture of both pectate lyase and APM resulted in a distinct phenotype, consisting of 'dumbbell'-shaped cells, as APM-induced swelling occurs at the novel expansion centers exposed by pectate lyase treatment. These cells also presented other curious alterations, including an extensive, chloroplast-free cytoplasmic zone at the center of the cell, a septum containing \u03b2-glycan, arabinogalactan and homogalacturonan epitopes, unique stacks of endoplasmic reticulum, displaced Golgi bodies, and an extensive network of vacuoles. These results provide insight into the importance of cell wall integrity in defining the location of cell growth and division in P. margaritaceum. Understanding these processes in a unicellular zygnematophyte may provide insights into steps involved in the evolution of land plants.", "doi": "10.1093/jxb/erae387", "pmid": "39269031", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "7756302"}], "notes": [], "created": "2024-11-15T12:08:05.360Z", "modified": "2025-11-05T13:54:08.964Z"}, {"entity": "publication", "iuid": "631321ade8c64aee894b30aeb0022924", "links": {"self": {"href": "https://publications.scilifelab.se/publication/631321ade8c64aee894b30aeb0022924.json"}, "display": {"href": "https://publications.scilifelab.se/publication/631321ade8c64aee894b30aeb0022924"}}, "title": "Insights into metabolic changes during epidermal differentiation as revealed by multiphoton microscopy with fluorescence lifetime imaging.", "authors": [{"family": "Malak", "given": "Monika", "initials": "M"}, {"family": "Qian", "given": "Chen", "initials": "C"}, {"family": "James", "given": "Jeemol", "initials": "J"}, {"family": "Nair", "given": "Syam", "initials": "S"}, {"family": "Grantham", "given": "Julie", "initials": "J"}, {"family": "Ericson", "given": "Marica B", "initials": "MB"}], "type": "journal article", "published": "2025-02-21", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "15", "issue": "1", "pages": "6377", "issn-l": "2045-2322"}, "abstract": "Rapid developments in the field of organotypic cultures have generated a growing need for effective and non-invasive methods for quality control during tissue development. In this study, we correlate metabolic changes with epidermal differentiation and demonstrate that multiphoton microscopy with fluorescence lifetime imaging (MPM-FLIM) can be applied to monitor epidermal differentiation of keratinocytes with respect to proliferative and differentiated states. In a 2D keratinocyte tissue culture model, increased expression of differentiation markers keratin-1 and keratin-10 was induced with calcium supplementation. An accompanying shift from glycolysis to mitochondrial respiration was detected in metabolic flux assays. Analysis of MPM-FLIM images acquired at 750 nm and 900 nm excitation revealed a decreased relative fraction of intracellular NADH and FAD after high calcium treatment, consistent with increased oxidative phosphorylation. Epidermal differentiation could be monitored over a 96 h period. Discrimination analysis based on k-means clustering generated clusters that correlated well with the duration of high Ca2+ treatment, suggesting that MPM-FLIM can provide useful parameters for monitoring keratinocyte differentiation.", "doi": "10.1038/s41598-025-90101-4", "pmid": "39984626", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11845624"}, {"db": "pii", "key": "10.1038/s41598-025-90101-4"}], "notes": [], "created": "2025-11-05T13:54:13.831Z", "modified": "2025-11-05T13:54:13.868Z"}, {"entity": "publication", "iuid": "58a0c3b2653b49d8b28daf5a2aa1c889", "links": {"self": {"href": "https://publications.scilifelab.se/publication/58a0c3b2653b49d8b28daf5a2aa1c889.json"}, "display": {"href": "https://publications.scilifelab.se/publication/58a0c3b2653b49d8b28daf5a2aa1c889"}}, "title": "Intranasal Delivery of a Ghrelin Mimetic Engages the Brain Ghrelin Signaling System in Mice.", "authors": [{"family": "Poelman", "given": "Ren\u00e9e", "initials": "R", "orcid": "0009-0004-8655-0026", "researcher": {"href": "https://publications.scilifelab.se/researcher/d826c2eaa44a4b859c1f48faa2e07621.json"}}, {"family": "Le May", "given": "Marie V", "initials": "MV", "orcid": "0000-0001-5563-9512", "researcher": {"href": "https://publications.scilifelab.se/researcher/0dad2e705cff43a4a7a1e3954f4452d7.json"}}, {"family": "Sch\u00e9le", "given": "Erik", "initials": "E", "orcid": "0000-0003-2693-7312", "researcher": {"href": "https://publications.scilifelab.se/researcher/4349f37c25c44b419ea6e27f17a1a9a1.json"}}, {"family": "Stoltenborg", "given": "Iris", "initials": "I", "orcid": "0000-0001-5134-8769", "researcher": {"href": "https://publications.scilifelab.se/researcher/50e7803a10d34b4284cd5ee8a3390413.json"}}, {"family": "Dickson", "given": "Suzanne L", "initials": "SL", "orcid": "0000-0002-3822-5294", "researcher": {"href": "https://publications.scilifelab.se/researcher/eabf6c037c6640cf95d64eebfb3f62e9.json"}}], "type": "journal article", "published": "2025-02-05", "journal": {"title": "Endocrinology", "issn": "1945-7170", "volume": "166", "issue": "3", "issn-l": "0013-7227"}, "abstract": "Ghrelin, the endogenous ligand of the growth hormone secretagogue receptor (GHSR), promotes food intake and other feeding behaviors, and stimulates growth hormone (GH) release from the pituitary. Growth hormone secretagogues (GHS), such as GHRP-6 and MK-0677, are synthetic GHSR ligands that activate orexigenic neuropeptide Y neurons that coexpress agouti-related peptide (AgRP) in the arcuate nucleus of the hypothalamus when administered systemically. Systemic GHRP-6 also stimulates GH release in humans and rats. Thus, GHS and ghrelin have therapeutic relevance in patients who could benefit from its orexigenic and/or GH-releasing effects. This study examined whether intranasal delivery of ghrelin, GHRP-6, or MK-0677 engages the brain ghrelin signaling system. Effective compounds and doses were selected based on increased food intake after intranasal application in mice. Only GHRP-6 (5 mg/kg) increased food intake without adverse effects, prompting detailed analysis of meal patterns, neuronal activation in the arcuate nucleus (via Fos mapping) and neurochemical identification of c-fos messenger RNA (mRNA)-expressing neurons using RNAscope. We also assessed the effect of intranasal GHRP-6 on serum GH levels. Intranasal GHRP-6 increased food intake by increasing meal frequency and size. Fos expression in the arcuate nucleus was higher in GHRP-6-treated mice than in saline controls. When examining the neurochemical identity of c-fos-mRNA-expressing neurons, we found coexpression with 63.5 \u00b1 1.9% Ghsr mRNA, 79 \u00b1 6.8% Agrp mRNA, and 11.4 \u00b1 2.5% Ghrh mRNA, demonstrating GHRP-6's ability to engage arcuate nucleus neurons involved in food intake and GH release. Additionally, intranasal GHRP-6 elevated GH serum levels. These findings suggest that intranasal GHRP-6, but not ghrelin or MK-0677, can engage the brain ghrelin signaling system.", "doi": "10.1210/endocr/bqae166", "pmid": "39813130", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11795113"}, {"db": "pii", "key": "7954553"}], "notes": [], "created": "2025-11-05T13:58:56.979Z", "modified": "2025-11-05T13:58:57.267Z"}, {"entity": "publication", "iuid": "bf9db0aeeb03448faeb36ffffcc747bd", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bf9db0aeeb03448faeb36ffffcc747bd.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bf9db0aeeb03448faeb36ffffcc747bd"}}, "title": "Unravelling the dominant role of phosphorylation degree in governing the functionality of reassembled casein micelles: Implications for future dairy production through precision fermentation", "authors": [{"family": "Che", "given": "Jing", "initials": "J", "orcid": "0000-0002-0489-0683", "researcher": {"href": "https://publications.scilifelab.se/researcher/6bdb1771dbaa4f4e987eafb1ac13d4bf.json"}}, {"family": "Fan", "given": "Zekun", "initials": "Z"}, {"family": "Bijl", "given": "Etske", "initials": "E", "orcid": "0000-0002-7363-5387", "researcher": {"href": "https://publications.scilifelab.se/researcher/0c7ccc5ea1184a81a40dff03ceca3191.json"}}, {"family": "Thomsen", "given": "Julia Prangchat Stub", "initials": "JPS", "orcid": "0009-0006-5703-2961", "researcher": {"href": "https://publications.scilifelab.se/researcher/8ad9e7e2c13c403eaba5922610b4f0e5.json"}}, {"family": "Mijakovic", "given": "Ivan", "initials": "I"}, {"family": "Hettinga", "given": "Kasper", "initials": "K", "orcid": "0000-0002-9017-4447", "researcher": {"href": "https://publications.scilifelab.se/researcher/d64330b9c6074a7998685d972c2d5dd1.json"}}, {"family": "Poulsen", "given": "Nina Aagaard", "initials": "NA"}, {"family": "Larsen", "given": "Lotte Bach", "initials": "LB", "orcid": "0000-0001-9674-0107", "researcher": {"href": "https://publications.scilifelab.se/researcher/3a1cd42b0d8d43a28ef0656a24e0c8c5.json"}}], "type": "journal-article", "published": "2025-02-00", "journal": {"title": "Food Hydrocolloids", "issn": "0268-005X", "volume": "159", "pages": "110615", "issn-l": null}, "abstract": null, "doi": "10.1016/j.foodhyd.2024.110615", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2025-11-05T13:48:07.147Z", "modified": "2025-11-05T13:48:07.492Z"}, {"entity": "publication", "iuid": "b4d32af19a9043ee95844d326c8fa800", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b4d32af19a9043ee95844d326c8fa800.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b4d32af19a9043ee95844d326c8fa800"}}, "title": "Reduced Alcohol Consumption Following Ablation of Cholinergic Interneurons in the Nucleus Accumbens of Wistar Rats.", "authors": [{"family": "Loft\u00e9n", "given": "Anna", "initials": "A"}, {"family": "Cadeddu", "given": "Davide", "initials": "D"}, {"family": "Danielsson", "given": "Klara", "initials": "K"}, {"family": "Stomberg", "given": "Rosita", "initials": "R"}, {"family": "Adermark", "given": "Louise", "initials": "L", "orcid": "0000-0002-7165-9908", "researcher": {"href": "https://publications.scilifelab.se/researcher/6602087739df48208b4ead747f6752ca.json"}}, {"family": "S\u00f6derpalm", "given": "Bo", "initials": "B"}, {"family": "Ericson", "given": "Mia", "initials": "M", "orcid": "0000-0002-7557-7109", "researcher": {"href": "https://publications.scilifelab.se/researcher/5b639bcd6dc44459a8cf95ff214ce74d.json"}}], "type": "journal article", "published": "2025-02-00", "journal": {"title": "Addict Biol", "issn": "1369-1600", "volume": "30", "issue": "2", "pages": "e70022", "issn-l": "1355-6215"}, "abstract": "Alcohol use disorder is a severe mental health condition causing medical consequences and preterm death. Alcohol activates the mesolimbic dopamine system leading to an increase of extracellular dopamine (DA) in the nucleus accumbens, an event that is associated with the reinforcing effects of alcohol. Cholinergic interneurons (CIN) are important modulators of accumbal DA signalling, and depletion of accumbal CIN attenuates the alcohol-induced increase in extracellular DA. The aim of this study was to explore the functional role of accumbal CIN in alcohol-related behaviour. To this end, ablation of CIN was induced by local administration of anticholine acetyltransferase-saporin bilaterally into the nucleus accumbens of male Wistar rats. Alcohol consumption in ablated and sham-treated rats was studied using a two-bottle-choice intermittent alcohol consumption paradigm. Rats with depleted CIN consumed significantly less alcohol than sham-treated controls. No differences in sucrose preference, motor activity, water intake or weight gain were noted between treatment groups, suggesting that the ablation selectively affected alcohol-related behaviour. In conclusion, this study further supports a role for accumbal CIN in regulating alcohol-consummatory behaviour.", "doi": "10.1111/adb.70022", "pmid": "39936333", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11815332"}], "notes": [], "created": "2025-11-05T13:54:06.250Z", "modified": "2025-11-05T13:54:06.411Z"}, {"entity": "publication", "iuid": "ce7ad1afa4874fc6bb73127f9cefddc0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ce7ad1afa4874fc6bb73127f9cefddc0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ce7ad1afa4874fc6bb73127f9cefddc0"}}, "title": "Phospho-tau serine-262 and serine-356 as biomarkers of pre-tangle soluble tau assemblies in Alzheimer's disease.", "authors": [{"family": "Islam", "given": "Tohidul", "initials": "T", "orcid": "0000-0003-1561-944X", "researcher": {"href": "https://publications.scilifelab.se/researcher/a0693554436c4017a605281f3d97d373.json"}}, {"family": "Hill", "given": "Emily", "initials": "E"}, {"family": "Abrahamson", "given": "Eric E", "initials": "EE"}, {"family": "Servaes", "given": "Stijn", "initials": "S"}, {"family": "Smirnov", "given": "Denis S", "initials": "DS"}, {"family": "Zeng", "given": "Xuemei", "initials": "X"}, {"family": "Sehrawat", "given": "Anuradha", "initials": "A"}, {"family": "Chen", "given": "Yijun", "initials": "Y", "orcid": "0009-0001-4579-4057", "researcher": {"href": "https://publications.scilifelab.se/researcher/0e7eb6e67f694af8b1dfb26c4dbcf97c.json"}}, {"family": "Kac", "given": "Przemys\u0142aw R", "initials": "PR", "orcid": "0000-0001-5083-0924", "researcher": {"href": "https://publications.scilifelab.se/researcher/d7d23b25a3774bb696abf5522147d249.json"}}, {"family": "Kvartsberg", "given": "Hlin", "initials": "H", "orcid": "0000-0002-4481-508X", "researcher": {"href": "https://publications.scilifelab.se/researcher/be021173500e46a59ec36f4b34ee607f.json"}}, {"family": "Olsson", "given": "Maria", "initials": "M"}, {"family": "Sjons", "given": "Emma", "initials": "E", "orcid": "0009-0008-5030-114X", "researcher": {"href": "https://publications.scilifelab.se/researcher/da9154ad214441e3adc4a094c7c73e32.json"}}, {"family": "Gonzalez-Ortiz", "given": "Fernando", "initials": "F", "orcid": "0000-0001-7897-9456", "researcher": {"href": "https://publications.scilifelab.se/researcher/c4bc7b2303004dcc81fe355d7c15bb4c.json"}}, {"family": "Therriault", "given": "Joseph", "initials": "J"}, {"family": "Tissot", "given": "C\u00e9cile", "initials": "C", "orcid": "0000-0003-2711-3833", "researcher": {"href": "https://publications.scilifelab.se/researcher/bbdaa319e358466696ff529d1221591d.json"}}, {"family": "Del Popolo", "given": "Ivana", "initials": "I", "orcid": "0009-0005-6480-4117", "researcher": {"href": "https://publications.scilifelab.se/researcher/2bd3286ad15640dcb5358891c82d0c7a.json"}}, {"family": "Rahmouni", "given": "Nesrine", "initials": "N"}, {"family": "Richardson", "given": "Abbie", "initials": "A"}, {"family": "Mitchell", "given": "Victoria", "initials": "V"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H", "orcid": "0000-0003-3930-4354", "researcher": {"href": "https://publications.scilifelab.se/researcher/85efee74eb4a4b38b63cf2823d204529.json"}}, {"family": "Pascoal", "given": "Tharick A", "initials": "TA", "orcid": "0000-0001-9057-8014", "researcher": {"href": "https://publications.scilifelab.se/researcher/2bfa45d39b324b2ab78c12ec044ebe48.json"}}, {"family": "Lashley", "given": "Tammaryn", "initials": "T", "orcid": "0000-0001-7389-0348", "researcher": {"href": "https://publications.scilifelab.se/researcher/533fe74a716840b2a55fddf0452f2a23.json"}}, {"family": "Wall", "given": "Mark J", "initials": "MJ"}, {"family": "Galasko", "given": "Douglas", "initials": "D"}, {"family": "Rosa-Neto", "given": "Pedro", "initials": "P", "orcid": "0000-0001-9116-1376", "researcher": {"href": "https://publications.scilifelab.se/researcher/2a2e4f85e17f45489cde7f8d8430daa4.json"}}, {"family": "Ikonomovic", "given": "Milos D", "initials": "MD"}, {"family": "Blennow", "given": "Kaj", "initials": "K", "orcid": "0000-0002-1890-4193", "researcher": {"href": "https://publications.scilifelab.se/researcher/5e646be026ce42ecbfd4d62eca3f9bce.json"}}, {"family": "Karikari", "given": "Thomas K", "initials": "TK", "orcid": "0000-0003-1422-4358", "researcher": {"href": "https://publications.scilifelab.se/researcher/cf3831a3e6a341f4b0a728e591de5b42.json"}}], "type": "journal article", "published": "2025-02-00", "journal": {"title": "Nat. Med.", "issn": "1546-170X", "volume": "31", "issue": "2", "pages": "574-588", "issn-l": "1078-8956"}, "abstract": "Patients with Alzheimer's disease (AD) with little or no quantifiable insoluble brain tau neurofibrillary tangle (NFT) pathology demonstrate stronger clinical benefits of therapies than those with advanced NFTs. The formation of NFTs can be prevented by targeting the intermediate soluble tau assemblies (STAs). However, biochemical understanding and biomarkers of STAs are lacking. We show that Tris-buffered saline-soluble tau aggregates from autopsy-verified AD brain tissues include the core sequence ~tau258-368. In neuropathological assessments, antibodies against the phosphorylation sites serine-262 and serine-356 within the STA core almost exclusively stained granular (that is, prefibrillar) tau aggregates in pre-NFTs while antibodies against phosphorylation at serine-202 and threonine-205 and threonine-231, outside the STA core, stained the entire spectrum of tau aggregates in pre-NFTs and mature NFTs, dystrophic neurites and neuropil threads in the hippocampus. Functionally, a recombinantly produced STA core peptide robustly altered neuronal excitability and synaptic transmission in mouse hippocampal brain slices. Furthermore, we developed a cerebrospinal fluid assay that differentiated STAs in AD from non-AD tauopathies, correlated with the severity of NFT burden and cognitive decline independently of amyloid beta deposition, and with tau positron emission tomography uptake across Braak NFT stages. Together, our findings inform about the status of early-stage tau aggregation, reveal aggregation-relevant phosphorylation epitopes in tau and offer a diagnostic biomarker and targeted therapeutic opportunities for AD.", "doi": "10.1038/s41591-024-03400-0", "pmid": "39930142", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11835754"}, {"db": "pii", "key": "10.1038/s41591-024-03400-0"}], "notes": [], "created": "2025-11-05T13:53:57.536Z", "modified": "2025-11-05T13:53:58.203Z"}, {"entity": "publication", "iuid": "8d4a8412b91143359d590e01636497ae", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8d4a8412b91143359d590e01636497ae.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8d4a8412b91143359d590e01636497ae"}}, "title": "Extracellular vesicle surface engineering with integrins (ITGAL & ITGB2) to specifically target ICAM-1-expressing endothelial cells.", "authors": [{"family": "Bergqvist", "given": "Markus", "initials": "M", "orcid": "0009-0003-5716-3716", "researcher": {"href": "https://publications.scilifelab.se/researcher/91d33e374d0642479a80683a989f095a.json"}}, {"family": "Park", "given": "Kyong-Su", "initials": "KS", "orcid": "0000-0003-0902-7800", "researcher": {"href": "https://publications.scilifelab.se/researcher/26e308b29fe144b49f4db27f4b819c18.json"}}, {"family": "Karimi", "given": "Nasibeh", "initials": "N", "orcid": "0000-0003-1499-6876", "researcher": {"href": "https://publications.scilifelab.se/researcher/14632eec875c42038aa0b6983e0ec107.json"}}, {"family": "Yu", "given": "Lijuan", "initials": "L", "orcid": "0000-0003-3558-3800", "researcher": {"href": "https://publications.scilifelab.se/researcher/8b0b4ca8553144b19c236bc09c1c9b81.json"}}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C", "orcid": "0000-0003-1279-1746", "researcher": {"href": "https://publications.scilifelab.se/researcher/e14e17d2cdb24a9f93991d83811c78b9.json"}}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J", "orcid": "0000-0001-9195-9249", "researcher": {"href": "https://publications.scilifelab.se/researcher/0cbcaf6b5698411c92e0de9e8fcf390f.json"}}], "type": "journal article", "published": "2025-01-30", "journal": {"title": "J Nanobiotechnology", "issn": "1477-3155", "volume": "23", "issue": "1", "pages": "64", "issn-l": null}, "abstract": "Extracellular vesicles (EVs) are taken up by most cells, however specific or preferential cell targeting remains a hurdle. This study aims to develop an EV that targets cells involved in inflammation, specifically those expressing intercellular adhesion molecule-1 (ICAM-1). To target these cells, we overexpress the ICAM-1 binding receptor \"lymphocyte function-associated antigen-1\" (LFA-1) in HEK293F cells, by sequential transfection of plasmids of the two LFA-1 subunits, ITGAL and ITGB2 (CD11a and CD18). The LFA-1 receptor was strongly overexpressed on the EVs released by the transfected cells. We further loaded these EVs with a therapeutic peptide, targeting myeloid differentiation primary response 88 (Myd88; EVMyd88), through a developed EV open-and-close procedure. Myd88 is a downstream common intracellular messenger for most TLR-receptors. EV expression of LFA-1 increases EV binding to ICAM-1-expressing cells, an effect that was dose-dependently inhibited by a specific neutralizing ICAM-1 antibody. Further, activated human endothelial cells treated with LFA-1 EVMyd88 had increased uptake of these EVs, resulting in dose-dependent inhibition of induced release of IL-8, presumably by targeting Myd88. We conclude that LFA-1-expressing EVMyd88 may be a candidate suitable for delivering therapeutic peptides in inflammatory diseases associated with TLR-activation.", "doi": "10.1186/s12951-025-03125-3", "pmid": "39885580", "labels": {"Glycoproteomics and MS Proteomics": "Service", "Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11780982"}, {"db": "pii", "key": "10.1186/s12951-025-03125-3"}], "notes": [], "created": "2025-10-23T13:06:45.347Z", "modified": "2025-11-05T13:48:02.553Z"}, {"entity": "publication", "iuid": "8dabe8b76a1242a79844e89147083cc1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8dabe8b76a1242a79844e89147083cc1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8dabe8b76a1242a79844e89147083cc1"}}, "title": "Stress granule formation is regulated by signaling machinery involving Sch9/Ypk1, sphingolipids, and Ubi4.", "authors": [{"family": "Chen", "given": "Lihua", "initials": "L"}, {"family": "Gao", "given": "Yuan", "initials": "Y"}, {"family": "Hao", "given": "Xinxin", "initials": "X"}, {"family": "Yang", "given": "Xiaoxue", "initials": "X"}, {"family": "Lindstr\u00f6m", "given": "Michelle", "initials": "M"}, {"family": "Jiang", "given": "Shan", "initials": "S"}, {"family": "Cao", "given": "Xiuling", "initials": "X"}, {"family": "Liu", "given": "Huisheng", "initials": "H"}, {"family": "Nystr\u00f6m", "given": "Thomas", "initials": "T"}, {"family": "Sunnerhagen", "given": "Per", "initials": "P"}, {"family": "Liu", "given": "Beidong", "initials": "B"}], "type": "journal article", "published": "2025-01-06", "journal": {"title": "Theranostics", "issn": "1838-7640", "volume": "15", "issue": "5", "pages": "1987-2005", "issn-l": null}, "abstract": "Rationale: Stress granules (SGs) are membraneless organelles that are formed in response to various stresses. Multiple cellular processes have been reported to be involved in SG formation. However, the signaling cascades that coordinate SG formation remain to be elucidated. Methods: By performing two high-content imaging-based phenomic screens, we identified multiple signaling components that form a possible signal transduction pathway that regulates SG formation. Results: We found that Sch9 and Ypk1 function in an early step of SG formation, leading to a decrease in intermediate long-chain base sphingolipids (LCBs). This further downregulates the polyubiquitin precursor protein Ubi4 through upregulating the deubiquitinase Ubp3. Decreased levels of cellular free ubiquitin may subsequently facilitate Lsm7 phase separation and thus trigger SG formation. Conclusion: The signaling pathway identified in this work, together with its conserved components, provides valuable clues for understanding the mechanisms underlying SG formation and SG-associated human diseases.", "doi": "10.7150/thno.98199", "pmid": "39897563", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11780528"}, {"db": "pii", "key": "thnov15p1987"}], "notes": [], "created": "2025-11-05T13:48:10.339Z", "modified": "2025-11-05T13:48:10.423Z"}, {"entity": "publication", "iuid": "b017843641ad4057b8fde4e7fc40569e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b017843641ad4057b8fde4e7fc40569e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b017843641ad4057b8fde4e7fc40569e"}}, "title": "A Non-Centrifugation Method to Concentrate and Purify Extracellular Vesicles Using Superabsorbent Polymer Followed by Size Exclusion Chromatography.", "authors": [{"family": "Bergqvist", "given": "Markus", "initials": "M", "orcid": "0009-0003-5716-3716", "researcher": {"href": "https://publications.scilifelab.se/researcher/91d33e374d0642479a80683a989f095a.json"}}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C", "orcid": "0000-0003-1279-1746", "researcher": {"href": "https://publications.scilifelab.se/researcher/e14e17d2cdb24a9f93991d83811c78b9.json"}}, {"family": "Crescitelli", "given": "Rossella", "initials": "R", "orcid": "0000-0002-1714-3169", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d4b955f26ca4a679deb090e30d0ccf1.json"}}, {"family": "Park", "given": "Kyong-Su", "initials": "KS", "orcid": "0000-0003-0902-7800", "researcher": {"href": "https://publications.scilifelab.se/researcher/26e308b29fe144b49f4db27f4b819c18.json"}}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J", "orcid": "0000-0001-9195-9249", "researcher": {"href": "https://publications.scilifelab.se/researcher/0cbcaf6b5698411c92e0de9e8fcf390f.json"}}], "type": "journal article", "published": "2025-01-00", "journal": {"title": "J Extracell Vesicles", "issn": "2001-3078", "volume": "14", "issue": "1", "pages": "e70037", "issn-l": "2001-3078"}, "abstract": "Extracellular vesicles (EVs) can be isolated and purified from cell cultures and biofluids using different methodologies. Here, we explored a novel EV isolation approach by combining superabsorbent polymers (SAP) in a dialysis membrane with size exclusion chromatography (SEC) to achieve high concentration and purity of EVs without the use of ultracentrifugation (UC). Suspension HEK293 cells transfected with CD63 coupled with Thermo Luciferase were used to quantify the EV yield and purity. The 500 mL conditioned medium volume was initially reduced by pressure ultrafiltration, followed by UC, SAP or a centrifugal filter unit (CFU). Using either of these methods, the EVs were concentrated to a final volume of approximately 1 mL, with retained functionality. The yield, quantified by luciferase activity, was highest with UC (70%-80%), followed by SAP (60%-70%) and CFU (50%-60%). Further purification of the EVs was performed by iodixanol density cushion (IDC) or SEC (Sepharose CL-2B or 6B, in either 10 or 20 mL columns). Although the IDC and Sepharose CL-2B (10 mL) achieved the highest yields, the purity was slightly higher (30%) with IDC. In conclusion, combining SAP concentration with CL-2B SEC is an alternative and efficient way to isolate EVs without using UC.", "doi": "10.1002/jev2.70037", "pmid": "39840900", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11752139"}], "notes": [], "created": "2025-11-05T13:48:00.099Z", "modified": "2025-11-05T13:48:00.169Z"}, {"entity": "publication", "iuid": "6a94871e098b4c1fbdc8171dd1e76fdf", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6a94871e098b4c1fbdc8171dd1e76fdf.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6a94871e098b4c1fbdc8171dd1e76fdf"}}, "title": "Transmembrane peptide-loaded ionic liquid nanocarriers for targeting ErbB2-positive cancer", "authors": [{"family": "Abujubara", "given": "Helal", "initials": "H"}, {"family": "Bharmoria", "given": "Pankaj", "initials": "P"}, {"family": "Alvarez", "given": "Samantha", "initials": "S"}, {"family": "Appiah", "given": "Enoch", "initials": "E", "orcid": "0000-0001-5712-1557", "researcher": {"href": "https://publications.scilifelab.se/researcher/541bffae79b0487c98d4c413c9dcf27a.json"}}, {"family": "Moth-Poulsen", "given": "Kasper", "initials": "K", "orcid": "0000-0003-4018-4927", "researcher": {"href": "https://publications.scilifelab.se/researcher/5807cc241ba24cf4a7841086d72dc3b9.json"}}, {"family": "Sayin", "given": "Volkan", "initials": "V"}, {"family": "Tietze", "given": "Alesia", "initials": "A", "orcid": "0000-0002-9281-548X", "researcher": {"href": "https://publications.scilifelab.se/researcher/2c9c55ec11d84630a4b4472cd21ef96b.json"}}], "type": "posted-content", "published": "2024-11-06", "journal": {"title": "chemrxiv", "issn": null, "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": null, "doi": "10.26434/chemrxiv-2024-wkw04", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2024-11-15T11:59:56.734Z", "modified": "2025-12-18T19:24:40.619Z"}, {"entity": "publication", "iuid": "a1e589510717452fb0536d9a1409bc40", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a1e589510717452fb0536d9a1409bc40.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a1e589510717452fb0536d9a1409bc40"}}, "title": "A new species of Erinaceusyllis (Annelida: Syllidae) discovered at a wood-fall in the eastern Clarion-Clipperton Zone, central Pacific Ocean.", "authors": [{"family": "Nilsson", "given": "Christian L", "initials": "CL", "orcid": "0009-0005-6356-2152", "researcher": {"href": "https://publications.scilifelab.se/researcher/692506bc15454c6c99126379028d6d6b.json"}}, {"family": "Wiklund", "given": "Helena", "initials": "H"}, {"family": "Glover", "given": "Adrian G", "initials": "AG"}, {"family": "Bribiesca-Contreras", "given": "Guadalupe", "initials": "G"}, {"family": "Dahlgren", "given": "Thomas G", "initials": "TG"}], "type": "journal-article", "published": "2024-11-00", "journal": {"title": "Deep Sea Research Part I: Oceanographic Research Papers", "issn": "0967-0637", "pages": "104415", "issn-l": null}, "abstract": null, "doi": "10.1016/j.dsr.2024.104415", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2024-11-15T12:09:44.886Z", "modified": "2025-12-04T19:30:22.879Z"}, {"entity": "publication", "iuid": "bb241ed48fe94700bafa1c93cc2bba33", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bb241ed48fe94700bafa1c93cc2bba33.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bb241ed48fe94700bafa1c93cc2bba33"}}, "title": "The crucial role of bioimage analysts in scientific research and publication.", "authors": [{"family": "Cimini", "given": "Beth A", "initials": "BA", "orcid": "0000-0001-9640-9318", "researcher": {"href": "https://publications.scilifelab.se/researcher/db23220ace18412a872eeedc98b6ca3d.json"}}, {"family": "Bankhead", "given": "Peter", "initials": "P", "orcid": "0000-0003-4851-8813", "researcher": {"href": "https://publications.scilifelab.se/researcher/677800a098f9480aad3629a35a6d7145.json"}}, {"family": "D'Antuono", "given": "Rocco", "initials": "R", "orcid": "0000-0003-0180-6500", "researcher": {"href": "https://publications.scilifelab.se/researcher/19a219cdf18a48c581c66844eed7f888.json"}}, {"family": "Fazeli", "given": "Elnaz", "initials": "E", "orcid": "0000-0002-0770-0777", "researcher": {"href": "https://publications.scilifelab.se/researcher/18bdf85441724603af3433b9ca2671a7.json"}}, {"family": "Fernandez-Rodriguez", "given": "Julia", "initials": "J", "orcid": "0000-0003-4522-0966", "researcher": {"href": "https://publications.scilifelab.se/researcher/3bd9c743e99d479cb752aeec947acab3.json"}}, {"family": "Fuster-Barcel\u00f3", "given": "Caterina", "initials": "C", "orcid": "0000-0002-4784-6957", "researcher": {"href": "https://publications.scilifelab.se/researcher/d79b3864cd2746e2b17df5513a86d75c.json"}}, {"family": "Haase", "given": "Robert", "initials": "R", "orcid": "0000-0001-5949-2327", "researcher": {"href": "https://publications.scilifelab.se/researcher/f99dc020f05f479cafa0aede600157f0.json"}}, {"family": "Jambor", "given": "Helena Klara", "initials": "HK", "orcid": "0000-0003-3397-1842", "researcher": {"href": "https://publications.scilifelab.se/researcher/4d9c995274164d5298f59dbd5c088ab7.json"}}, {"family": "Jones", "given": "Martin L", "initials": "ML", "orcid": "0000-0003-0994-5652", "researcher": {"href": "https://publications.scilifelab.se/researcher/b0007265969c41f48df95f3c74897453.json"}}, {"family": "Jug", "given": "Florian", "initials": "F", "orcid": "0000-0002-8499-5812", "researcher": {"href": "https://publications.scilifelab.se/researcher/40ccce2be15f4d8fab6a75615ebc1246.json"}}, {"family": "Klemm", "given": "Anna H", "initials": "AH", "orcid": "0000-0002-3466-1320", "researcher": {"href": "https://publications.scilifelab.se/researcher/4ae78afb2a424b0ab70d49871f361d13.json"}}, {"family": "Kreshuk", "given": "Anna", "initials": "A", "orcid": "0000-0003-1334-6388", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ae251ba20e04f1eab188633a94e49bd.json"}}, {"family": "Marcotti", "given": "Stefania", "initials": "S", "orcid": "0000-0002-2877-0133", "researcher": {"href": "https://publications.scilifelab.se/researcher/150857cd632243249afeba74751e0c22.json"}}, {"family": "Martins", "given": "Gabriel G", "initials": "GG", "orcid": "0000-0002-6506-9776", "researcher": {"href": "https://publications.scilifelab.se/researcher/c04a08e246854401b529158afe9de318.json"}}, {"family": "McArdle", "given": "Sara", "initials": "S", "orcid": "0000-0003-3795-3772", "researcher": {"href": "https://publications.scilifelab.se/researcher/93aa1ff33b784bd0bfa75b471cdb54df.json"}}, {"family": "Miura", "given": "Kota", "initials": "K", "orcid": "0000-0001-6926-191X", "researcher": {"href": "https://publications.scilifelab.se/researcher/d2924dc08df743e188b5ead9a88449a6.json"}}, {"family": "Mu\u00f1oz-Barrutia", "given": "Arrate", "initials": "A", "orcid": "0000-0002-1573-1661", "researcher": {"href": "https://publications.scilifelab.se/researcher/55b6136b104f46ad958ffe4aa41b9714.json"}}, {"family": "Murphy", "given": "Laura C", "initials": "LC", "orcid": "0000-0003-0029-0434", "researcher": {"href": "https://publications.scilifelab.se/researcher/5bf84771f58b47839a2d1a39961c83f3.json"}}, {"family": "Nelson", "given": "Michael S", "initials": "MS", "orcid": "0000-0003-0480-5597", "researcher": {"href": "https://publications.scilifelab.se/researcher/3897b6add2a340e19ad1e051f08931c5.json"}}, {"family": "N\u00f8rrelykke", "given": "Simon F", "initials": "SF", "orcid": "0000-0001-8302-526X", "researcher": {"href": "https://publications.scilifelab.se/researcher/76912657154446a988bbcbdd146b9877.json"}}, {"family": "Paul-Gilloteaux", "given": "Perrine", "initials": "P", "orcid": "0000-0002-4822-165X", "researcher": {"href": "https://publications.scilifelab.se/researcher/cc1aedddd2484c60b1e6bcf3aff9262a.json"}}, {"family": "Pengo", "given": "Thomas", "initials": "T", "orcid": "0000-0002-9632-918X", "researcher": {"href": "https://publications.scilifelab.se/researcher/150939b6bb54471fa96434ef52fe8d7e.json"}}, {"family": "Pylv\u00e4n\u00e4inen", "given": "Joanna W", "initials": "JW", "orcid": "0000-0002-3540-5150", "researcher": {"href": "https://publications.scilifelab.se/researcher/b86cf81244ee420b9f00a654709bbfda.json"}}, {"family": "Pytowski", "given": "Lior", "initials": "L", "orcid": "0000-0002-8530-5123", "researcher": {"href": "https://publications.scilifelab.se/researcher/c808c56b5e0a431dae719c6e4feb70e1.json"}}, {"family": "Ravera", "given": "Arianna", "initials": "A", "orcid": "0009-0006-6585-261X", "researcher": {"href": "https://publications.scilifelab.se/researcher/2873293a0e174e0599374a7ba9516787.json"}}, {"family": "Reinke", "given": "Annika", "initials": "A", "orcid": "0000-0003-4363-1876", "researcher": {"href": "https://publications.scilifelab.se/researcher/ac4e522151164f09aac3b83068537ea1.json"}}, {"family": "Rekik", "given": "Yousr", "initials": "Y", "orcid": "0009-0001-1405-7257", "researcher": {"href": "https://publications.scilifelab.se/researcher/d8284d7240fa4f57ade366fd602623e0.json"}}, {"family": "Strambio-De-Castillia", "given": "Caterina", "initials": "C", "orcid": "0000-0002-1069-1816", "researcher": {"href": "https://publications.scilifelab.se/researcher/d56f91373ceb40bab6bae2635961bdf5.json"}}, {"family": "Th\u00e9di\u00e9", "given": "Daniel", "initials": "D", "orcid": "0000-0002-1352-7245", "researcher": {"href": "https://publications.scilifelab.se/researcher/b504b532ff944ab9ab72329adc6282fd.json"}}, {"family": "Uhlmann", "given": "Virginie", "initials": "V", "orcid": "0000-0002-2859-9241", "researcher": {"href": "https://publications.scilifelab.se/researcher/c4215607e1ed4f18b2809de6c5e34df6.json"}}, {"family": "Umney", "given": "Oliver", "initials": "O", "orcid": "0009-0005-2321-9413", "researcher": {"href": "https://publications.scilifelab.se/researcher/2ed29415dcf34d69b863d06e8edaa256.json"}}, {"family": "Wiggins", "given": "Laura", "initials": "L", "orcid": "0000-0003-4615-2379", "researcher": {"href": "https://publications.scilifelab.se/researcher/dbdc5616fe8542638669cbd647c46bb9.json"}}, {"family": "Eliceiri", "given": "Kevin W", "initials": "KW", "orcid": "0000-0001-8678-670X", "researcher": {"href": "https://publications.scilifelab.se/researcher/acb896fcca6a49b096068c3b5294624d.json"}}], "type": "journal article", "published": "2024-10-15", "journal": {"title": "J. Cell. Sci.", "issn": "1477-9137", "volume": "137", "issue": "20", "issn-l": "0021-9533"}, "abstract": "Bioimage analysis (BIA), a crucial discipline in biological research, overcomes the limitations of subjective analysis in microscopy through the creation and application of quantitative and reproducible methods. The establishment of dedicated BIA support within academic institutions is vital to improving research quality and efficiency and can significantly advance scientific discovery. However, a lack of training resources, limited career paths and insufficient recognition of the contributions made by bioimage analysts prevent the full realization of this potential. This Perspective - the result of the recent The Company of Biologists Workshop 'Effectively Communicating Bioimage Analysis', which aimed to summarize the global BIA landscape, categorize obstacles and offer possible solutions - proposes strategies to bring about a cultural shift towards recognizing the value of BIA by standardizing tools, improving training and encouraging formal credit for contributions. We also advocate for increased funding, standardized practices and enhanced collaboration, and we conclude with a call to action for all stakeholders to join efforts in advancing BIA.", "doi": "10.1242/jcs.262322", "pmid": "39475207", "labels": {"BioImage Informatics": "Collaborative", "Integrated Microscopy Technologies Gothenburg": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "362545"}], "notes": [], "created": "2024-11-13T10:08:24.614Z", "modified": "2024-11-15T12:02:35.328Z"}, {"entity": "publication", "iuid": "67f7141c96474ec1bb0e2619dd27f05f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/67f7141c96474ec1bb0e2619dd27f05f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/67f7141c96474ec1bb0e2619dd27f05f"}}, "title": "De novo production of protoberberine and benzophenanthridine alkaloids through metabolic engineering of yeast.", "authors": [{"family": "Jiao", "given": "Xiang", "initials": "X", "orcid": "0000-0001-8043-3719", "researcher": {"href": "https://publications.scilifelab.se/researcher/405364bbdf444b598c5bc13a3c6e4426.json"}}, {"family": "Fu", "given": "Xiaozhi", "initials": "X", "orcid": "0000-0002-4465-7528", "researcher": {"href": "https://publications.scilifelab.se/researcher/cdb3c34994ca41afa148487fc571aa8d.json"}}, {"family": "Li", "given": "Qishuang", "initials": "Q", "orcid": "0000-0002-2148-7917", "researcher": {"href": "https://publications.scilifelab.se/researcher/7afb27a365e047039b7134b38461d4bc.json"}}, {"family": "Bu", "given": "Junling", "initials": "J"}, {"family": "Liu", "given": "Xiuyu", "initials": "X"}, {"family": "Savolainen", "given": "Otto", "initials": "O"}, {"family": "Huang", "given": "Luqi", "initials": "L"}, {"family": "Guo", "given": "Juan", "initials": "J", "orcid": "0000-0002-1327-4428", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f6b24fad40f4fe480512aa9da62682a.json"}}, {"family": "Nielsen", "given": "Jens", "initials": "J", "orcid": "0000-0002-9955-6003", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a596e289be4438a8a2653b1f25fea8b.json"}}, {"family": "Chen", "given": "Yun", "initials": "Y", "orcid": "0000-0002-2146-6008", "researcher": {"href": "https://publications.scilifelab.se/researcher/c8a0c4c96b7e491496aa0991c7e9a460.json"}}], "type": "journal article", "published": "2024-10-09", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "15", "issue": "1", "pages": "8759", "issn-l": "2041-1723"}, "abstract": "Protoberberine alkaloids and benzophenanthridine alkaloids (BZDAs) are subgroups of benzylisoquinoline alkaloids (BIAs), which represent a diverse class of plant-specialized natural metabolites with many pharmacological properties. Microbial biosynthesis has been allowed for accessibility and scalable production of high-value BIAs. Here, we engineer Saccharomyces cerevisiae to de novo produce a series of protoberberines and BZDAs, including palmatine, berberine, chelerythrine, sanguinarine and chelirubine. An ER compartmentalization strategy is developed to improve vacuole protein berberine bridge enzyme (BBE) activity, resulting in >200% increase on the production of the key intermediate (S)-scoulerine. Another promiscuous vacuole protein dihydrobenzophenanthridine oxidase (DBOX) has been identified to catalyze two-electron oxidation on various tetrahydroprotoberberines at N7-C8 position and dihydrobenzophenanthridine alkaloids. Furthermore, cytosolically expressed DBOX can alleviate the limitation on BBE. This study highlights the potential of microbial cell factories for the biosynthesis of a diverse group of BIAs through engineering of heterologous plant enzymes.", "doi": "10.1038/s41467-024-53045-3", "pmid": "39384562", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service", "Chalmers Mass Spectrometry Infrastructure": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC11464499"}, {"db": "pii", "key": "10.1038/s41467-024-53045-3"}], "notes": [], "created": "2024-11-15T12:07:09.645Z", "modified": "2024-11-27T15:29:12.299Z"}, {"entity": "publication", "iuid": "3c64bee47a294d36978d8ebdc7fe0da0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3c64bee47a294d36978d8ebdc7fe0da0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3c64bee47a294d36978d8ebdc7fe0da0"}}, "title": "Analyzing Fusion Pore Dynamics and Counting the Number of Acetylcholine Molecules Released by Exocytosis.", "authors": [{"family": "Wang", "given": "Yuanmo", "initials": "Y"}, {"family": "Pradhan", "given": "Ajay", "initials": "A"}, {"family": "Gupta", "given": "Pankaj", "initials": "P"}, {"family": "Hanrieder", "given": "J\u00f6rg", "initials": "J"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H"}, {"family": "Cans", "given": "Ann-Sofie", "initials": "AS", "orcid": "0000-0002-3059-2399", "researcher": {"href": "https://publications.scilifelab.se/researcher/a5d51dca363f4bbfb78fa34e79c142e9.json"}}], "type": "journal article", "published": "2024-09-25", "journal": {"title": "J. Am. Chem. Soc.", "issn": "1520-5126", "volume": "146", "issue": "38", "pages": "25902-25906", "issn-l": "0002-7863"}, "abstract": "Acetylcholine (ACh) is a critical neurotransmitter influencing various neurophysiological functions. Despite its significance, quantitative methods with adequate spatiotemporal resolution for recording a single exocytotic ACh efflux are lacking. In this study, we introduce an ultrafast amperometric ACh biosensor that enables 50 kHz electrochemical recording of spontaneous single exocytosis events at axon terminals of differentiated cholinergic human SH-SY5Y neuroblastoma cells with sub-millisecond temporal resolution. Characterization of the recorded amperometric traces revealed seven distinct current spike types, each displaying variations in shape, time scale, and ACh quantities released. This finding suggests that exocytotic release is governed by complex fusion pore dynamics in these cells. The absolute number of ACh molecules released during exocytosis was quantified by calibrating the sensor through the electroanalysis of liposomes preloaded with varying ACh concentrations. Notably, the largest quantal release involving approximately 8000 ACh molecules likely represents full exocytosis, while a smaller release of 5000 ACh molecules may indicate partial exocytosis. Following a local administration of bafilomycin A1, a V-ATPase inhibitor, the cholinergic cells exhibited both a larger quantity of ACh released and a higher frequency of exocytosis events. Therefore, this ACh sensor provides a means to monitor minute amounts of ACh and investigate regulatory release mechanisms at the single-cell level, which is vital for understanding healthy brain function and pathologies and optimizing drug treatment for disorders.", "doi": "10.1021/jacs.4c08450", "pmid": "39259049", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11440489"}], "notes": [], "created": "2024-11-15T12:11:44.473Z", "modified": "2024-11-15T12:11:44.587Z"}, {"entity": "publication", "iuid": "dfd1a9d2a5a0470487fbd391c8c9a14f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/dfd1a9d2a5a0470487fbd391c8c9a14f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/dfd1a9d2a5a0470487fbd391c8c9a14f"}}, "title": "PITAR, a DNA damage-inducible cancer/testis long noncoding RNA, inactivates p53 by binding and stabilizing TRIM28 mRNA.", "authors": [{"family": "Jana", "given": "Samarjit", "initials": "S", "orcid": "0000-0002-8743-4711", "researcher": {"href": "https://publications.scilifelab.se/researcher/903a167caef746238e1bff8c592383a3.json"}}, {"family": "Mondal", "given": "Mainak", "initials": "M"}, {"family": "Mahale", "given": "Sagar", "initials": "S"}, {"family": "Gupta", "given": "Bhavana", "initials": "B"}, {"family": "Prasasvi", "given": "Kaval Reddy", "initials": "KR"}, {"family": "Kandasami", "given": "Lekha", "initials": "L"}, {"family": "Jha", "given": "Neha", "initials": "N"}, {"family": "Chowdhury", "given": "Abhishek", "initials": "A", "orcid": "0009-0007-2985-9053", "researcher": {"href": "https://publications.scilifelab.se/researcher/3f468e7899da4e22bdfade6fd2015b3c.json"}}, {"family": "Santosh", "given": "Vani", "initials": "V"}, {"family": "Kanduri", "given": "Chandrasekhar", "initials": "C"}, {"family": "Somasundaram", "given": "Kumaravel", "initials": "K", "orcid": "0000-0001-6228-9741", "researcher": {"href": "https://publications.scilifelab.se/researcher/1510e866f99c493b8b7df15dac2085d3.json"}}], "type": "journal article", "published": "2024-09-20", "journal": {"title": "Elife", "issn": "2050-084X", "volume": "12", "issn-l": "2050-084X"}, "abstract": "In tumors with WT p53, alternate mechanisms of p53 inactivation are reported. Here, we have identified a long noncoding RNA, PITAR (p53 Inactivating TRIM28 Associated RNA), as an inhibitor of p53. PITAR is an oncogenic Cancer/testis lncRNA and is highly expressed in glioblastoma (GBM) and glioma stem-like cells (GSC). We establish that TRIM28 mRNA, which encodes a p53-specific E3 ubiquitin ligase, is a direct target of PITAR. PITAR interaction with TRIM28 RNA stabilized TRIM28 mRNA, which resulted in increased TRIM28 protein levels and reduced p53 steady-state levels due to enhanced p53 ubiquitination. DNA damage activated PITAR, in addition to p53, in a p53-independent manner, thus creating an incoherent feedforward loop to inhibit the DNA damage response by p53. While PITAR silencing inhibited the growth of WT p53 containing GSCs in vitro and reduced glioma tumor growth in vivo, its overexpression enhanced the tumor growth in a TRIM28-dependent manner and promoted resistance to Temozolomide. Thus, we establish an alternate way of p53 inactivation by PITAR, which maintains low p53 levels in normal cells and attenuates the DNA damage response by p53. Finally, we propose PITAR as a potential GBM therapeutic target.", "doi": "10.7554/eLife.88256", "pmid": "39302097", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11415074"}, {"db": "pii", "key": "88256"}, {"db": "Dryad", "key": "10.5061/dryad.3j9kd51t7"}], "notes": [], "created": "2024-11-15T12:06:55.291Z", "modified": "2024-11-15T12:06:55.461Z"}, {"entity": "publication", "iuid": "dd85f7399cac4a4d9b23caad506cb636", "links": {"self": {"href": "https://publications.scilifelab.se/publication/dd85f7399cac4a4d9b23caad506cb636.json"}, "display": {"href": "https://publications.scilifelab.se/publication/dd85f7399cac4a4d9b23caad506cb636"}}, "title": "The CCT\u03b4 subunit of the molecular chaperone CCT is required for correct localisation of p150Glued to spindle poles during mitosis.", "authors": [{"family": "C\u00f3rdoba-Beldad", "given": "Carmen M", "initials": "CM"}, {"family": "Grantham", "given": "Julie", "initials": "J"}], "type": "journal article", "published": "2024-09-00", "journal": {"title": "Eur J Cell Biol", "issn": "1618-1298", "volume": "103", "issue": "3", "pages": "151430", "issn-l": null}, "abstract": "Chaperonin Containing Tailless complex polypeptide 1 (CCT) is a molecular chaperone composed of eight distinct subunits that can exist as individual monomers or as components of a double oligomeric ring, which is essential for the folding of actin and tubulin and other substrates. Here we assess the role of CCT subunits in the context of cell cycle progression by individual subunit depletions upon siRNA treatment in mammalian cells. The depletion of individual CCT subunits leads to variation in the distribution of cell cycle phases and changes in mitotic index. Mitotic defects, such as unaligned chromosomes occur when CCT\u03b4 is depleted, concurrent with a reduction in spindle pole-localised p150Glued, a component of the dynactin complex and a binding partner of monomeric CCT\u03b4. In CCT\u03b4-depleted cells, changes in the elution profile of p150Glued are observed consistent with altered conformations and or assembly states with the dynactin complex. Addition of monomeric CCT\u03b4, in the form of GFP-CCT\u03b4, restores correct p150Glued localisation to the spindle poles and rescues the mitotic segregation defects that occur when CCT\u03b4 is depleted. This study demonstrates a requirement for CCT\u03b4 in its monomeric form for correct chromosome segregation via a mechanism that promotes the correct localisation of p150Glued, thus revealing further complexities to the interplay between CCT, tubulin folding and microtubule dynamics.", "doi": "10.1016/j.ejcb.2024.151430", "pmid": "38897036", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S0171-9335(24)00047-5"}], "notes": [], "created": "2024-11-15T12:03:09.550Z", "modified": "2024-11-15T12:03:09.575Z"}, {"entity": "publication", "iuid": "5a883dca0eb24d879489a60342dd3bfd", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5a883dca0eb24d879489a60342dd3bfd.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5a883dca0eb24d879489a60342dd3bfd"}}, "title": "Expression of inducible nitric oxide synthase, nitrotyrosine, eosinophilic peroxidase, eotaxin-3, and galectin-3 in patients with gastroesophageal reflux disease, eosinophilic esophagitis, and in healthy controls: a semiquantitative image analysis of 3,3'-diaminobenzidine-stained esophageal biopsies.", "authors": [{"family": "Plate", "given": "John", "initials": "J", "orcid": "0009-0009-1988-2561", "researcher": {"href": "https://publications.scilifelab.se/researcher/ec80cb7ee8e84fc4a44c38ae98786ca4.json"}}, {"family": "Bove", "given": "Mogens", "initials": "M"}, {"family": "Larsson", "given": "Helen M", "initials": "HM"}, {"family": "Norder Grusell", "given": "Elisabeth", "initials": "E"}, {"family": "Chatterjee", "given": "Nabanita", "initials": "N"}, {"family": "Johansson", "given": "Leif E", "initials": "LE"}, {"family": "Bergquist", "given": "Henrik", "initials": "H"}], "type": "journal article", "published": "2024-08-29", "journal": {"title": "Dis Esophagus", "issn": "1442-2050", "volume": "37", "issue": "9", "issn-l": null}, "abstract": "Eosinophilic esophagitis (EoE) and gastroesophageal reflux disease (GERD) share many histopathological features; therefore, markers for differentiation are of diagnostic interest and may add to the understanding of the underlying mechanisms. The nitrergic system is upregulated in GERD and probably also in EoE. Esophageal biopsies of patients with EoE (n = 20), GERD (n = 20), and healthy volunteers (HVs) (n = 15) were exposed to antibodies against inducible nitric oxide synthase (iNOS), nitrotyrosine, eosinophilic peroxidase, eotaxin-3, and galectin-3. The stained object glasses were randomized, digitized, and blindly analyzed regarding the expression of DAB (3,3'-diaminobenzidine) by a protocol developed in QuPath software. A statistically significant overexpression of iNOS was observed in patients with any of the two inflammatory diseases compared with that in HVs. Eotaxin-3 could differentiate HVs versus inflammatory states. Gastroesophageal reflux patients displayed the highest levels of nitrotyrosine. Neither iNOS nor nitrotyrosine alone were able to differentiate between the two diseases. For that purpose, eosinophil peroxidase was a better candidate, as the mean levels increased stepwise from HVs via GERD to EoE. iNOS and nitrotyrosine are significantly overexpressed in patients with EoE and GERD compared with healthy controls, but only eosinophil peroxidase could differentiate the two types of esophagitis. The implications of the finding of the highest levels of nitrotyrosine among gastroesophageal reflux patients are discussed.", "doi": "10.1093/dote/doae034", "pmid": "38679488", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11360979"}, {"db": "pii", "key": "7659427"}], "notes": [], "created": "2024-11-15T12:10:08.680Z", "modified": "2024-11-15T12:10:08.842Z"}, {"entity": "publication", "iuid": "ecc798da00bd489298e00c1eb42e9dad", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ecc798da00bd489298e00c1eb42e9dad.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ecc798da00bd489298e00c1eb42e9dad"}}, "title": "Migratory CD103+CD11b+ cDC2s in Peyer's patches are critical for gut IgA responses following oral immunization.", "authors": [{"family": "Gribonika", "given": "Inta", "initials": "I"}, {"family": "Str\u00f6mberg", "given": "Anneli", "initials": "A"}, {"family": "Chandode", "given": "Rakesh K", "initials": "RK"}, {"family": "Sch\u00f6n", "given": "Karin", "initials": "K"}, {"family": "Lahl", "given": "Katharina", "initials": "K"}, {"family": "Bemark", "given": "Mats", "initials": "M"}, {"family": "Lycke", "given": "Nils", "initials": "N"}], "type": "journal article", "published": "2024-08-00", "journal": {"title": "Mucosal Immunol", "issn": "1935-3456", "volume": "17", "issue": "4", "pages": "509-523", "issn-l": "1933-0219"}, "abstract": "Induction and regulation of specific intestinal immunoglobulin (Ig)A responses critically depend on dendritic cell (DC) subsets and the T cells they activate in the Peyer's patches (PP). We found that oral immunization with cholera toxin (CT) as an adjuvant resulted in migration-dependent changes in the composition and localization of PP DC subsets with increased numbers of cluster of differentiation (CD)103- conventional DC (cDC)2s and lysozyme-expressing DC (LysoDCs) in the subepithelial dome and of CD103+ cDC2s that expressed CD101 in the T cell zones, while oral ovalbumin (OVA) tolerization was instead associated with greater accumulation of cDC1s and peripherally induced regulatory T cells (pTregs) in this area. Decreased IgA responses were observed after CT-adjuvanted immunization in huCD207DTA mice lacking CD103+ cDC2s, while oral OVA tolerization was inefficient in cDC1-deficient Batf3-/- mice. Using OVA transgenic T cell receptor CD4 T cell adoptive transfer models, we found that co-transferred endogenous wildtype CD4 T cells can hinder the induction of OVA-specific IgA responses through secretion of interleukin-10. CT could overcome this blocking effect, apparently through a modulating effect on pTregs while promoting an expansion of follicular helper T cells. The data support a model where cDC1-induced pTreg normally suppresses PP responses for any given antigen and where CT's oral adjuvanticity effect is dependent on promoting follicular helper T cell responses through induction of CD103+ cDC2s.", "doi": "10.1016/j.mucimm.2024.03.004", "pmid": "38492746", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S1933-0219(24)00023-0"}], "notes": [], "created": "2024-11-15T12:05:07.359Z", "modified": "2024-11-15T12:05:07.363Z"}, {"entity": "publication", "iuid": "a28a213490064713ad542662610169a6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a28a213490064713ad542662610169a6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a28a213490064713ad542662610169a6"}}, "title": "Aging AdipoR2-deficient mice are hyperactive with enlarged brains excessively rich in saturated fatty acids.", "authors": [{"family": "Ruiz", "given": "Mario", "initials": "M", "orcid": "0000-0002-7149-6600", "researcher": {"href": "https://publications.scilifelab.se/researcher/35ea5372ccf64bad864d90e4b3698a24.json"}}, {"family": "Devkota", "given": "Ranjan", "initials": "R", "orcid": "0009-0001-6289-7891", "researcher": {"href": "https://publications.scilifelab.se/researcher/28f5086847c74fafbecac69a028f14a4.json"}}, {"family": "Bergh", "given": "Per-Olof", "initials": "PO", "orcid": "0000-0001-9993-6965", "researcher": {"href": "https://publications.scilifelab.se/researcher/28c1f37dc6cc4ed98c8e8eb1a621fa2c.json"}}, {"family": "Nik", "given": "Ali Moussavi", "initials": "AM"}, {"family": "Blid Sk\u00f6ldheden", "given": "Sebastian", "initials": "S"}, {"family": "Mondejar-Duran", "given": "Jorge", "initials": "J"}, {"family": "Tufvesson-Alm", "given": "Maximilian", "initials": "M"}, {"family": "Bohlooly-Y", "given": "Mohammad", "initials": "M"}, {"family": "Sanchez", "given": "Diego", "initials": "D"}, {"family": "Carlsson", "given": "Peter", "initials": "P"}, {"family": "Henricsson", "given": "Marcus", "initials": "M", "orcid": "0000-0002-4202-0339", "researcher": {"href": "https://publications.scilifelab.se/researcher/01a323cbf0a24269bd32bfc34539e021.json"}}, {"family": "Jerlhag", "given": "Elisabet", "initials": "E", "orcid": "0000-0003-2408-3165", "researcher": {"href": "https://publications.scilifelab.se/researcher/072e685dbffe46a4aa857740467e867a.json"}}, {"family": "Bor\u00e9n", "given": "Jan", "initials": "J", "orcid": "0000-0003-0786-8091", "researcher": {"href": "https://publications.scilifelab.se/researcher/1e85f6d287ce4c60a7b35b287efb4f79.json"}}, {"family": "Pilon", "given": "Marc", "initials": "M", "orcid": "0000-0003-3919-2882", "researcher": {"href": "https://publications.scilifelab.se/researcher/d45c4ecf9afe463c971af2de53a770a8.json"}}], "type": "journal article", "published": "2024-07-31", "journal": {"title": "FASEB J.", "issn": "1530-6860", "volume": "38", "issue": "14", "pages": "e23815", "issn-l": "0892-6638"}, "abstract": "To investigate how the fatty acid composition of brain phospholipids influences brain-specific processes, we leveraged the AdipoR2 (adiponectin receptor 2) knockout mouse model in which the brain is enlarged, and cellular membranes are excessively rich in saturated fatty acids. Lipidomics analysis of brains at 2, 7, and 18 months of age showed that phosphatidylcholines, which make up about two-thirds of all cerebrum membrane lipids, contain a gross excess of saturated fatty acids in AdipoR2 knockout mice, and that this is mostly attributed to an excess palmitic acid (C16:0) at the expense of oleic acid (C18:1), consistent with a defect in fatty acid desaturation and elongation in the mutant. Specifically, there was a ~12% increase in the overall saturated fatty acid content within phosphatidylcholines and a ~30% increase in phosphatidylcholines containing two palmitic acids. Phosphatidylethanolamines, sphingomyelins, ceramides, lactosylceramides, and dihydroceramides also showed an excess of saturated fatty acids in the AdipoR2 knockout mice while nervonic acid (C24:1) was enriched at the expense of shorter saturated fatty acids in glyceroceramides. Similar defects were found in the cerebellum and myelin sheaths. Histology showed that cell density is lower in the cerebrum of AdipoR2 knockout mice, but electron microscopy did not detect reproducible defects in the ultrastructure of cerebrum neurons, though proteomics analysis showed an enrichment of electron transport chain proteins in the cerebellum. Behavioral tests showed that older (33 weeks old) AdipoR2 knockout mice are hyperactive and anxious compared to control mice of a similar age. Also, in contrast to control mice, the AdipoR2 knockout mice do not gain weight in old age but do have normal lifespans. We conclude that an excess fatty acid saturation in brain phospholipids is accompanied by hyperactivity but seems otherwise well tolerated.", "doi": "10.1096/fj.202400293RR", "pmid": "38989587", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2024-11-15T12:10:51.341Z", "modified": "2024-11-15T12:10:51.835Z"}, {"entity": "publication", "iuid": "123c7ce0304c4077b97f1dac22148d57", "links": {"self": {"href": "https://publications.scilifelab.se/publication/123c7ce0304c4077b97f1dac22148d57.json"}, "display": {"href": "https://publications.scilifelab.se/publication/123c7ce0304c4077b97f1dac22148d57"}}, "title": "Correlated multimodal imaging in life sciences: lessons learnt", "authors": [{"family": "Rudraiah", "given": "Pavitra Sokke", "initials": "PS"}, {"family": "Camacho", "given": "Rafael", "initials": "R", "orcid": "0000-0003-2325-6407", "researcher": {"href": "https://publications.scilifelab.se/researcher/6a7a8cfe28634821984b078ce3246343.json"}}, {"family": "Fernandez-Rodriguez", "given": "Julia", "initials": "J", "orcid": "0000-0003-4522-0966", "researcher": {"href": "https://publications.scilifelab.se/researcher/3bd9c743e99d479cb752aeec947acab3.json"}}, {"family": "Fixler", "given": "Dror", "initials": "D"}, {"family": "Grimm", "given": "Jan", "initials": "J"}, {"family": "Gruber", "given": "Florian", "initials": "F"}, {"family": "Kala\u0161", "given": "Mat\u00fa\u0161", "initials": "M", "orcid": "0000-0002-1509-4981", "researcher": {"href": "https://publications.scilifelab.se/researcher/ee56816d10554890a6045b9705974854.json"}}, {"family": "Kremslehner", "given": "Christopher", "initials": "C"}, {"family": "Kuntner", "given": "Claudia", "initials": "C"}, {"family": "Kuzdas-Wood", "given": "Daniela", "initials": "D"}, {"family": "Lindblad", "given": "Joakim", "initials": "J", "orcid": "0000-0001-7312-8222", "researcher": {"href": "https://publications.scilifelab.se/researcher/c6b66ce110794e1fb312b82e790646b4.json"}}, {"family": "Mannheim", "given": "Julia G", "initials": "JG"}, {"family": "Marchetti-Deschmann", "given": "Martina", "initials": "M"}, {"family": "Paul-Gilloteaux", "given": "Perrine", "initials": "P", "orcid": "0000-0002-4822-165X", "researcher": {"href": "https://publications.scilifelab.se/researcher/cc1aedddd2484c60b1e6bcf3aff9262a.json"}}, {"family": "Sampaio", "given": "Paula", "initials": "P"}, {"family": "Sandbichler", "given": "Peter", "initials": "P"}, {"family": "Sartori-Rupp", "given": "Anna", "initials": "A"}, {"family": "Sladoje", "given": "Nata\u0161a", "initials": "N"}, {"family": "Verkade", "given": "Paul", "initials": "P"}, {"family": "Walter", "given": "Andreas", "initials": "A"}, {"family": "Zoratto", "given": "Samuele", "initials": "S"}], "type": "journal-article", "published": "2024-07-30", "journal": {"title": "Front. Biomater. Sci.", "issn": "2813-3749", "volume": "3", "issn-l": null}, "abstract": null, "doi": "10.3389/fbiom.2024.1338115", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2024-11-15T12:10:32.853Z", "modified": "2025-12-04T19:38:49.888Z"}, {"entity": "publication", "iuid": "8bb60e7586944b438ecbd4d8c35d287d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8bb60e7586944b438ecbd4d8c35d287d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8bb60e7586944b438ecbd4d8c35d287d"}}, "title": "Bifidobacterium longum subsp. longum BG-L47 boosts growth and activity of Limosilactobacillus reuteri DSM 17938 and its extracellular membrane vesicles.", "authors": [{"family": "Ermann Lundberg", "given": "Ludwig", "initials": "L", "orcid": "0000-0001-5983-1771", "researcher": {"href": "https://publications.scilifelab.se/researcher/ccb47fe370d24b30b505f75583167a9f.json"}}, {"family": "Pallabi Mishra", "given": "Punya", "initials": "P"}, {"family": "Liu", "given": "Peidi", "initials": "P"}, {"family": "Forsberg", "given": "Manuel Mata", "initials": "MM"}, {"family": "Sverremark-Ekstr\u00f6m", "given": "Eva", "initials": "E"}, {"family": "Grompone", "given": "Gianfranco", "initials": "G"}, {"family": "H\u00e5kansson", "given": "Sebastian", "initials": "S"}, {"family": "Linninge", "given": "Caroline", "initials": "C"}, {"family": "Roos", "given": "Stefan", "initials": "S", "orcid": "0000-0002-1606-1794", "researcher": {"href": "https://publications.scilifelab.se/researcher/3ab7209c1ebe40d8bdcc73f99fb44b29.json"}}], "type": "journal article", "published": "2024-07-24", "journal": {"title": "Appl. Environ. Microbiol.", "issn": "1098-5336", "volume": "90", "issue": "7", "pages": "e0024724", "issn-l": "0099-2240"}, "abstract": "The aim of this study was to identify a Bifidobacterium strain that improves the performance of Limosilactobacillus reuteri DSM 17938. Initial tests showed that Bifidobacterium longum subsp. longum strains boosted the growth of DSM 17938 during in vivo-like conditions. Further characterization revealed that one of the strains, BG-L47, had better bile and acid tolerance compared to BG-L48, as well as mucus adhesion compared to both BG-L48 and the control strain BB536. BG-L47 also had the capacity to metabolize a broad range of carbohydrates and sugar alcohols. Mapping of glycoside hydrolase (GH) genes of BG-L47 and BB536 revealed many GHs associated with plant-fiber utilization. However, BG-L47 had a broader phenotypic fiber utilization capacity. In addition, B. longum subsp. longum cells boosted the bioactivity of extracellular membrane vesicles (MV) produced by L. reuteri DSM 17938 during co-cultivation. Secreted 5'-nucleotidase (5'NT), an enzyme that converts AMP into the signal molecule adenosine, was increased in MV boosted by BG-L47. The MV exerted an improved antagonistic effect on the pain receptor transient receptor potential vanilloid 1 (TRPV1) and increased the expression of the immune development markers IL-6 and IL-1\u00df in a peripheral blood mononuclear cell (PBMC) model. Finally, the safety of BG-L47 was evaluated both by genome safety assessment and in a human safety study. Microbiota analysis showed that the treatment did not induce significant changes in the composition. In conclusion, B. longum subsp. longum BG-L47 has favorable physiological properties, can boost the in vitro activity of L. reuteri DSM 17938, and is safe for consumption, making it a candidate for further evaluation in probiotic studies.\n\nBy using probiotics that contain a combination of strains with synergistic properties, the likelihood of achieving beneficial interactions with the host can increase. In this study, we first performed a broad screening of Bifidobacterium longum subsp. longum strains in terms of synergistic potential and physiological properties. We identified a superior strain, BG-L47, with favorable characteristics and potential to boost the activity of the known probiotic strain Limosilactobacillus reuteri DSM 17938. Furthermore, we demonstrated that BG-L47 is safe for consumption in a human randomized clinical study and by performing a genome safety assessment. This work illustrates that bacteria-bacteria interactions differ at the strain level and further provides a strategy for finding and selecting companion strains of probiotics.", "doi": "10.1128/aem.00247-24", "pmid": "38888338", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11267924"}], "notes": [], "created": "2024-11-15T12:04:05.736Z", "modified": "2024-11-15T12:04:05.866Z"}, {"entity": "publication", "iuid": "8ee541ec736840ee8b67d897d9b8467f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8ee541ec736840ee8b67d897d9b8467f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8ee541ec736840ee8b67d897d9b8467f"}}, "title": "Neonatal microbiota colonization drives maturation of primary and secondary goblet cell mediated protection in the pre-weaning colon.", "authors": [{"family": "Johansson", "given": "\u00c5sa", "initials": "\u00c5"}, {"family": "Subramani", "given": "Mahadevan Venkita", "initials": "MV"}, {"family": "Yilmaz", "given": "Bahtiyar", "initials": "B"}, {"family": "Nystr\u00f6m", "given": "Elisabeth", "initials": "E"}, {"family": "Layunta", "given": "Elena", "initials": "E"}, {"family": "Arike", "given": "Liisa", "initials": "L"}, {"family": "Sommer", "given": "Felix", "initials": "F"}, {"family": "Rosenstiel", "given": "Philip", "initials": "P"}, {"family": "Vereecke", "given": "Lars", "initials": "L"}, {"family": "Holm", "given": "Louise Manner\u00e5s", "initials": "LM"}, {"family": "Wullaert", "given": "Andy", "initials": "A"}, {"family": "Pelaseyed", "given": "Thaher", "initials": "T"}, {"family": "Johansson", "given": "Malin E V", "initials": "MEV"}, {"family": "Birchenough", "given": "George M H", "initials": "GMH"}], "type": "journal article", "published": "2024-07-05", "journal": {"title": "bioRxiv", "issn": "2692-8205", "issn-l": null}, "abstract": "In the distal colon, mucus secreting goblet cells primarily confer protection from luminal microorganisms via generation of a sterile inner mucus layer barrier structure. Bacteria-sensing sentinel goblet cells provide a secondary defensive mechanism that orchestrates mucus secretion in response to microbes that breach the mucus barrier. Previous reports have identified mucus barrier deficiencies in adult germ-free mice, thus implicating a fundamental role for the microbiota in programming mucus barrier generation. In this study, we have investigated the natural neonatal development of the mucus barrier and sentinel goblet cell-dependent secretory responses upon postnatal colonization. Combined in vivo and ex vivo analyses of pre- and post-weaning colonic mucus barrier and sentinel goblet cell maturation demonstrated a sequential microbiota-dependent development of these primary and secondary goblet cell-intrinsic protective functions, with dynamic changes in mucus processing dependent on innate immune signalling via MyD88, and development of functional sentinel goblet cells dependent on the NADPH/Dual oxidase family member Duox2. Our findings therefore identify new mechanisms of microbiota-goblet cell regulatory interaction and highlight the critical importance of the pre-weaning period for the normal development of colonic barrier function.", "doi": "10.1101/2024.07.03.601781", "pmid": "39005291", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11245021"}, {"db": "pii", "key": "2024.07.03.601781"}], "notes": [], "created": "2024-11-15T12:07:24.602Z", "modified": "2024-11-15T12:07:24.719Z"}, {"entity": "publication", "iuid": "42bcd4fe16cb418cb721bdb519cafd34", "links": {"self": {"href": "https://publications.scilifelab.se/publication/42bcd4fe16cb418cb721bdb519cafd34.json"}, "display": {"href": "https://publications.scilifelab.se/publication/42bcd4fe16cb418cb721bdb519cafd34"}}, "title": "Pyrene Functionalized Norbornadiene-Quadricyclane Fluorescent Photoswitches: Characterization of their Spectral Properties and Application in Imaging of Amyloid Beta Plaques.", "authors": [{"family": "Ghasemi", "given": "Shima", "initials": "S"}, {"family": "Shamsabadi", "given": "Monika", "initials": "M"}, {"family": "Olesund", "given": "Axel", "initials": "A"}, {"family": "Najera", "given": "Francisco", "initials": "F"}, {"family": "Erbs Hillers-Bendtsen", "given": "Andreas", "initials": "A"}, {"family": "Edhborg", "given": "Fredrik", "initials": "F"}, {"family": "Aslam", "given": "Adil S", "initials": "AS"}, {"family": "Larsson", "given": "Wera", "initials": "W"}, {"family": "Wang", "given": "Zhihang", "initials": "Z"}, {"family": "Amombo Noa", "given": "Francoise M", "initials": "FM"}, {"family": "Salthouse", "given": "Rebecca Jane", "initials": "RJ"}, {"family": "\u00d6hrstr\u00f6m", "given": "Lars", "initials": "L"}, {"family": "H\u00f6lzel", "given": "Helen", "initials": "H"}, {"family": "Perez-Inestrosa", "given": "E", "initials": "E"}, {"family": "Mikkelsen", "given": "Kurt V", "initials": "KV"}, {"family": "Hanrieder", "given": "J\u00f6rg", "initials": "J"}, {"family": "Albinsson", "given": "Bo", "initials": "B"}, {"family": "Dreos", "given": "Ambra", "initials": "A", "orcid": "0000-0003-0448-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/11d65a7542cd443982e123ab00d46e9a.json"}}, {"family": "Moth-Poulsen", "given": "Kasper", "initials": "K"}], "type": "journal article", "published": "2024-06-17", "journal": {"title": "Chemistry", "issn": "1521-3765", "volume": "30", "issue": "34", "pages": "e202400322", "issn-l": "0947-6539"}, "abstract": "This study presents the synthesis and characterization of two fluorescent norbornadiene (NBD) photoswitches, each incorporating two conjugated pyrene units. Expanding on the limited repertoire of reported photoswitchable fluorescent NBDs, we explore their properties with a focus on applications in bioimaging of amyloid beta (A\u03b2) plaques. While the fluorescence emission of the NBD decreases upon photoisomerization, aligning with what has been previously reported, for the first time we observed luminescence after irradiation of the quadricyclane (QC) isomer. We deduce how the observed emission is induced by photoisomerization to the excited state of the parent isomer (NBD) which is then the emitting species. Thorough characterizations including NMR, UV-Vis, fluorescence, X-ray structural analysis and density functional theory (DFT) calculations provide a comprehensive understanding of these systems. Notably, one NBD-QC system exhibits exceptional durability. Additionally, these molecules serve as effective fluorescent stains targeting A\u03b2 plaques in situ, with observed NBD/QC switching within the plaques. Molecular docking simulations explore NBD interactions with amyloid, unveiling novel binding modes. These insights mark a crucial advancement in the comprehension and design of future photochromic NBDs for bioimaging applications and beyond, emphasizing their potential in studying and addressing protein aggregates.", "doi": "10.1002/chem.202400322", "pmid": "38629212", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2024-11-15T12:04:45.049Z", "modified": "2024-11-15T12:04:45.059Z"}, {"entity": "publication", "iuid": "077873a5c13a4c2d8c6ee269ac8d8c83", "links": {"self": {"href": "https://publications.scilifelab.se/publication/077873a5c13a4c2d8c6ee269ac8d8c83.json"}, "display": {"href": "https://publications.scilifelab.se/publication/077873a5c13a4c2d8c6ee269ac8d8c83"}}, "title": "Exposing kinetic disparities between inflammasome readouts using time-resolved analysis.", "authors": [{"family": "Herring", "given": "Matthew", "initials": "M"}, {"family": "Persson", "given": "Alexander", "initials": "A"}, {"family": "Potter", "given": "Ryan", "initials": "R"}, {"family": "Karlsson", "given": "Roger", "initials": "R"}, {"family": "S\u00e4rndahl", "given": "Eva", "initials": "E"}, {"family": "Ejdeb\u00e4ck", "given": "Mikael", "initials": "M"}], "type": "journal article", "published": "2024-06-15", "journal": {"title": "Heliyon", "issn": "2405-8440", "volume": "10", "issue": "11", "pages": "e32023", "issn-l": "2405-8440"}, "abstract": "The NLRP3 inflammasome is an intracellular multiprotein complex described to be involved in both an effective host response to infectious agents and various diseases. Investigation into the NLRP3 inflammasome has been extensive in the past two decades, and often revolves around the analysis of a few specific readouts, including ASC-speck formation, caspase-1 cleavage or activation, and cleavage and release of IL-1\u03b2 and/or IL-18. Quantification of these readouts is commonly undertaken as an endpoint analysis, where the presence of each positive outcome is assessed independently of the others. In this study, we apply time-resolved analysis of a human macrophage model (differentiated THP-1-ASC-GFP cells) to commonly accessible methods. This approach yields the additional quantifiable metrics time-resolved absolute change and acceleration, allowing comparisons between readouts. Using this methodological approach, we reveal (potential) discrepancies between inflammasome-related readouts that otherwise might go undiscovered. The study highlights the importance of time-resolved data in general and may be further extended as well as incorporated into other areas of research.", "doi": "10.1016/j.heliyon.2024.e32023", "pmid": "38867997", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11168392"}, {"db": "pii", "key": "S2405-8440(24)08054-X"}], "notes": [], "created": "2024-11-15T12:06:24.978Z", "modified": "2024-11-15T12:06:24.999Z"}, {"entity": "publication", "iuid": "46a4bd22d9ec44f4b08a35ba95cf2f70", "links": {"self": {"href": "https://publications.scilifelab.se/publication/46a4bd22d9ec44f4b08a35ba95cf2f70.json"}, "display": {"href": "https://publications.scilifelab.se/publication/46a4bd22d9ec44f4b08a35ba95cf2f70"}}, "title": "Intestinal Ketogenesis and Permeability.", "authors": [{"family": "Casselbrant", "given": "Anna", "initials": "A", "orcid": "0000-0001-7514-7435", "researcher": {"href": "https://publications.scilifelab.se/researcher/994b2b65cd154b359f5228eb0c69828b.json"}}, {"family": "Elias", "given": "Erik", "initials": "E"}, {"family": "Hallersund", "given": "Peter", "initials": "P"}, {"family": "Elebring", "given": "Erik", "initials": "E"}, {"family": "Cervin", "given": "Jakob", "initials": "J", "orcid": "0000-0002-3840-1008", "researcher": {"href": "https://publications.scilifelab.se/researcher/4d047b72260449fdb783eae2c96370eb.json"}}, {"family": "F\u00e4ndriks", "given": "Lars", "initials": "L", "orcid": "0000-0003-0736-3034", "researcher": {"href": "https://publications.scilifelab.se/researcher/32daf05ef1f541cbbdf0b4de2fbd142e.json"}}, {"family": "Wallenius", "given": "Ville", "initials": "V", "orcid": "0000-0001-8668-3196", "researcher": {"href": "https://publications.scilifelab.se/researcher/e728cf3f550046a590066de0e0cd47aa.json"}}], "type": "journal article", "published": "2024-06-14", "journal": {"title": "Int J Mol Sci", "issn": "1422-0067", "volume": "25", "issue": "12", "issn-l": null}, "abstract": "Consumption of a high-fat diet (HFD) has been suggested as a contributing factor behind increased intestinal permeability in obesity, leading to increased plasma levels of microbial endotoxins and, thereby, increased systemic inflammation. We and others have shown that HFD can induce jejunal expression of the ketogenic rate-limiting enzyme mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS). HMGCS is activated via the free fatty acid binding nuclear receptor PPAR-\u03b1, and it is a key enzyme in ketone body synthesis that was earlier believed to be expressed exclusively in the liver. The function of intestinal ketogenesis is unknown but has been described in suckling rats and mice pups, possibly in order to allow large molecules, such as immunoglobulins, to pass over the intestinal barrier. Therefore, we hypothesized that ketone bodies could regulate intestinal barrier function, e.g., via regulation of tight junction proteins. The primary aim was to compare the effects of HFD that can induce intestinal ketogenesis to an equicaloric carbohydrate diet on inflammatory responses, nutrition sensing, and intestinal permeability in human jejunal mucosa. Fifteen healthy volunteers receiving a 2-week HFD diet compared to a high-carbohydrate diet were compared. Blood samples and mixed meal tests were performed at the end of each dietary period to examine inflammation markers and postprandial endotoxemia. Jejunal biopsies were assessed for protein expression using Western blotting, immunohistochemistry, and morphometric characteristics of tight junctions by electron microscopy. Functional analyses of permeability and ketogenesis were performed in Caco-2 cells, mice, and human enteroids. Ussing chambers were used to analyze permeability. CRP and ALP values were within normal ranges and postprandial endotoxemia levels were low and did not differ between the two diets. The PPAR\u03b1 receptor was ketone body-dependently reduced after HFD. None of the tight junction proteins studied, nor the basal electrical parameters, were different between the two diets. However, the ketone body inhibitor hymeglusin increased resistance in mucosal biopsies. In addition, the tight junction protein claudin-3 was increased by ketone inhibition in human enteroids. The ketone body \u03b2-Hydroxybutyrate (\u03b2HB) did not, however, change the mucosal transition of the large-size molecular FD4-probe or LPS in Caco-2 and mouse experiments. We found that PPAR\u03b1 expression was inhibited by the ketone body \u03b2HB. As PPAR\u03b1 regulates HMGCS expression, the ketone bodies thus exert negative feedback signaling on their own production. Furthermore, ketone bodies were involved in the regulation of permeability on intestinal mucosal cells in vitro and ex vivo. We were not, however, able to reproduce these effects on intestinal permeability in vivo in humans when comparing two weeks of high-fat with high-carbohydrate diet in healthy volunteers. Further, neither the expression of inflammation markers nor the aggregate tight junction proteins were changed. Thus, it seems that not only HFD but also other factors are needed to permit increased intestinal permeability in vivo. This indicates that the healthy gut can adapt to extremes of macro-nutrients and increased levels of intestinally produced ketone bodies, at least during a shorter dietary challenge.", "doi": "10.3390/ijms25126555", "pmid": "38928261", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11204016"}, {"db": "pii", "key": "ijms25126555"}], "notes": [], "created": "2024-11-15T12:02:22.117Z", "modified": "2024-11-15T12:02:22.208Z"}, {"entity": "publication", "iuid": "4deb438b26af4bddbf57dee49f870159", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4deb438b26af4bddbf57dee49f870159.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4deb438b26af4bddbf57dee49f870159"}}, "title": "Chemical signatures delineate heterogeneous amyloid plaque populations across the Alzheimer's disease spectrum.", "authors": [{"family": "Koutarapu", "given": "Srinivas", "initials": "S", "orcid": "0000-0002-4355-6733", "researcher": {"href": "https://publications.scilifelab.se/researcher/79cb4df7812041b8ad57fbdd6bc42f01.json"}}, {"family": "Ge", "given": "Junyue", "initials": "J"}, {"family": "Dulewicz", "given": "Maciej", "initials": "M"}, {"family": "Srikrishna", "given": "Meera", "initials": "M"}, {"family": "Szadziewska", "given": "Alicja", "initials": "A"}, {"family": "Wood", "given": "Jack", "initials": "J"}, {"family": "Blennow", "given": "Kaj", "initials": "K"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H", "orcid": "0000-0003-3930-4354", "researcher": {"href": "https://publications.scilifelab.se/researcher/85efee74eb4a4b38b63cf2823d204529.json"}}, {"family": "Michno", "given": "Wojciech", "initials": "W", "orcid": "0000-0002-3096-3604", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b4307eb6e45426e8176337e88c9c344.json"}}, {"family": "Ryan", "given": "Natalie S", "initials": "NS"}, {"family": "Lashley", "given": "Tammaryn", "initials": "T"}, {"family": "Savas", "given": "Jeffrey", "initials": "J"}, {"family": "Sch\u00f6ll", "given": "Michael", "initials": "M", "orcid": "0000-0001-7800-1781", "researcher": {"href": "https://publications.scilifelab.se/researcher/2332043f0c4142309890b37050498c0c.json"}}, {"family": "Hanrieder", "given": "J\u00f6rg", "initials": "J", "orcid": "0000-0001-6059-198X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e65454100674f98bf8f2575093f2441.json"}}], "type": "journal article", "published": "2024-06-03", "journal": {"title": "bioRxiv", "issn": "2692-8205", "issn-l": null}, "abstract": "Amyloid plaque deposition is recognized as the primary pathological hallmark of Alzheimer's disease(AD) that precedes other pathological events and cognitive symptoms. Plaque pathology represents itself with an immense polymorphic variety comprising plaques with different stages of amyloid fibrillization ranging from diffuse to fibrillar, mature plaques. The association of polymorphic A\u03b2 plaque pathology with AD pathogenesis, clinical symptoms and disease progression remains unclear. Advanced chemical imaging tools, such as functional amyloid microscopy combined with MALDI mass spectrometry imaging (MSI), are now enhanced by deep learning algorithms. This integration allows for precise delineation of polymorphic plaque structures and detailed identification of their associated A\u03b2 compositions. We here set out to make use of these tools to interrogate heterogenic plaque types and their associated biochemical architecture. Our findings reveal distinct A\u03b2 signatures that differentiate diffuse plaques from fibrilized ones, with the latter showing substantially higher levels of A\u03b2x-40. Notably, within the fibrilized category, we identified a distinct subtype known as coarse-grain plaques. Both in sAD and fAD brain tissue, coarse grain plaques contained more A\u03b2x-40 and less A\u03b2x-42 compared with cored plaques. The coarse grain plaques in both sAD and fAD also showed higher levels of neuritic content including paired helical filaments (PHF-1)/phosphorylated phospho Tau-immunopositive neurites. Finally, the A\u03b2 peptide content in coarse grain plaques resembled that of vascular A\u03b2 deposits (CAA) though with relatively higher levels of A\u03b21-42 and pyroglutamated A\u03b2x-40 and A\u03b2x-42 species in coarse grain plaques. This is the first of its kind study on spatial in situ biochemical characterization of different plaque morphotypes demonstrating the potential of the correlative imaging techniques used that further increase the understanding of heterogeneous AD pathology. Linking the biochemical characteristics of amyloid plaque polymorphisms with various AD etiologies and toxicity mechanisms is crucial. Understanding the connection between plaque structure and disease pathogenesis can enhance our insights. This knowledge is particularly valuable for developing and advancing novel, amyloid-targeting therapeutics.", "doi": "10.1101/2024.06.03.596890", "pmid": "38895368", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11185524"}, {"db": "pii", "key": "2024.06.03.596890"}], "notes": [], "created": "2024-11-15T12:07:53.119Z", "modified": "2024-11-15T12:07:54.065Z"}, {"entity": "publication", "iuid": "4bc9858d38a840fe988055684f31af50", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4bc9858d38a840fe988055684f31af50.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4bc9858d38a840fe988055684f31af50"}}, "title": "Recognising the importance and impact of Imaging Scientists: Global guidelines for establishing career paths within core facilities.", "authors": [{"family": "Wright", "given": "Graham D", "initials": "GD", "orcid": "0000-0003-2362-1312", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ed99c3e988f47a6af856c324f20a358.json"}}, {"family": "Thompson", "given": "Kerry A", "initials": "KA"}, {"family": "Reis", "given": "Yara", "initials": "Y", "orcid": "0000-0001-9607-0991", "researcher": {"href": "https://publications.scilifelab.se/researcher/870a289e98f9406c859c84e9c94d52a2.json"}}, {"family": "Bischof", "given": "Johanna", "initials": "J"}, {"family": "Hockberger", "given": "Philip Edward", "initials": "PE", "orcid": "0000-0002-4013-4885", "researcher": {"href": "https://publications.scilifelab.se/researcher/80efd697b6e04a64a12c6d2adb1f1250.json"}}, {"family": "Itano", "given": "Michelle S", "initials": "MS", "orcid": "0000-0001-6853-1228", "researcher": {"href": "https://publications.scilifelab.se/researcher/75fbed7bb21246e78f47288f654ef31e.json"}}, {"family": "Yen", "given": "Lisa", "initials": "L", "orcid": "0000-0002-8394-1708", "researcher": {"href": "https://publications.scilifelab.se/researcher/5cad6a52c1744ce6975b6a219a82dfc0.json"}}, {"family": "Adelodun", "given": "Stephen Taiye", "initials": "ST"}, {"family": "Bialy", "given": "Nikki", "initials": "N", "orcid": "0000-0001-9681-9632", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f36538779df484ba612e5c8ab43de00.json"}}, {"family": "Brown", "given": "Claire M", "initials": "CM"}, {"family": "Chaabane", "given": "Linda", "initials": "L"}, {"family": "Chew", "given": "Teng-Leong", "initials": "TL", "orcid": "0000-0002-3139-7560", "researcher": {"href": "https://publications.scilifelab.se/researcher/8408e97b4a7042a6892eb4ed1d55276f.json"}}, {"family": "Chitty", "given": "Andrew I", "initials": "AI"}, {"family": "Cordeli\u00e8res", "given": "Fabrice P", "initials": "FP", "orcid": "0000-0002-5383-5816", "researcher": {"href": "https://publications.scilifelab.se/researcher/cd3da472e85b4b19897bc513e443219f.json"}}, {"family": "De Niz", "given": "Mariana", "initials": "M"}, {"family": "Ellenberg", "given": "Jan", "initials": "J"}, {"family": "Engelbrecht", "given": "Lize", "initials": "L"}, {"family": "Fabian-Morales", "given": "Eunice", "initials": "E"}, {"family": "Fazeli", "given": "Elnaz", "initials": "E"}, {"family": "Fernandez-Rodriguez", "given": "Julia", "initials": "J"}, {"family": "Ferrando-May", "given": "Elisa", "initials": "E"}, {"family": "Fletcher", "given": "Georgina", "initials": "G"}, {"family": "Galloway", "given": "Graham John", "initials": "GJ", "orcid": "0000-0002-0805-2775", "researcher": {"href": "https://publications.scilifelab.se/researcher/0246d819396446408614c9005d3f841f.json"}}, {"family": "Guerrero", "given": "Adan", "initials": "A"}, {"family": "Guimar\u00e3es", "given": "Jander Matos", "initials": "JM"}, {"family": "Jacobs", "given": "Caron A", "initials": "CA"}, {"family": "Jayasinghe", "given": "Sachintha", "initials": "S", "orcid": "0000-0002-3254-4892", "researcher": {"href": "https://publications.scilifelab.se/researcher/d72f702245c34ac39dee607093ade5b8.json"}}, {"family": "Kable", "given": "Eleanor", "initials": "E"}, {"family": "Kitten", "given": "Gregory T", "initials": "GT"}, {"family": "Komoto", "given": "Shinya", "initials": "S"}, {"family": "Ma", "given": "Xiaoxiao", "initials": "X"}, {"family": "Marques", "given": "J\u00e9ssica Ara\u00fajo", "initials": "JA"}, {"family": "Millis", "given": "Bryan A", "initials": "BA"}, {"family": "Miranda", "given": "Kildare", "initials": "K"}, {"family": "JohnO'Toole", "given": "Peter", "initials": "P"}, {"family": "Olatunji", "given": "Sunday Yinka", "initials": "SY"}, {"family": "Paina", "given": "Federica", "initials": "F"}, {"family": "Pollak", "given": "Cora Noemi", "initials": "CN", "orcid": "0009-0000-4540-9393", "researcher": {"href": "https://publications.scilifelab.se/researcher/19bcc89dbd9841589a6895d5b1aecce5.json"}}, {"family": "Prats", "given": "Clara", "initials": "C"}, {"family": "Pylv\u00e4n\u00e4inen", "given": "Joanna W", "initials": "JW", "orcid": "0000-0002-3540-5150", "researcher": {"href": "https://publications.scilifelab.se/researcher/b86cf81244ee420b9f00a654709bbfda.json"}}, {"family": "Rahmoon", "given": "Mai Atef", "initials": "MA"}, {"family": "Reiche", "given": "Michael A", "initials": "MA"}, {"family": "Riches", "given": "James Douglas", "initials": "JD"}, {"family": "Rossi", "given": "Andres Hugo", "initials": "AH"}, {"family": "Salamero", "given": "Jean", "initials": "J"}, {"family": "Thiriet", "given": "Caroline", "initials": "C"}, {"family": "Terjung", "given": "Stefan", "initials": "S", "orcid": "0000-0002-0018-1804", "researcher": {"href": "https://publications.scilifelab.se/researcher/421172838f5144fd96b39cb9ecaeaa6b.json"}}, {"family": "Vasconcelos", "given": "Aldenora Dos Santos", "initials": "ADS"}, {"family": "Keppler", "given": "Antje", "initials": "A"}], "type": "journal article", "published": "2024-06-00", "journal": {"title": "J Microsc", "issn": "1365-2818", "volume": "294", "issue": "3", "pages": "397-410", "issn-l": null}, "abstract": "In the dynamic landscape of scientific research, imaging core facilities are vital hubs propelling collaboration and innovation at the technology development and dissemination frontier. Here, we present a collaborative effort led by Global BioImaging (GBI), introducing international recommendations geared towards elevating the careers of Imaging Scientists in core facilities. Despite the critical role of Imaging Scientists in modern research ecosystems, challenges persist in recognising their value, aligning performance metrics and providing avenues for career progression and job security. The challenges encompass a mismatch between classic academic career paths and service-oriented roles, resulting in a lack of understanding regarding the value and impact of Imaging Scientists and core facilities and how to evaluate them properly. They further include challenges around sustainability, dedicated training opportunities and the recruitment and retention of talent. Structured across these interrelated sections, the recommendations within this publication aim to propose globally applicable solutions to navigate these challenges. These recommendations apply equally to colleagues working in other core facilities and research institutions through which access to technologies is facilitated and supported. This publication emphasises the pivotal role of Imaging Scientists in advancing research programs and presents a blueprint for fostering their career progression within institutions all around the world.", "doi": "10.1111/jmi.13307", "pmid": "38691400", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2024-11-15T12:12:01.314Z", "modified": "2024-11-15T12:12:02.168Z"}, {"entity": "publication", "iuid": "36d5252e331c487cb68d957705e9c9f6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/36d5252e331c487cb68d957705e9c9f6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/36d5252e331c487cb68d957705e9c9f6"}}, "title": "Proteomic profiling of polyglucosan bodies associated with glycogenin-1 deficiency in skeletal muscle.", "authors": [{"family": "Visuttijai", "given": "Kittichate", "initials": "K", "orcid": "0000-0002-4800-8533", "researcher": {"href": "https://publications.scilifelab.se/researcher/f41f59ad2b0a4e1c95b0cc9cf109f6fa.json"}}, {"family": "Hedberg-Oldfors", "given": "Carola", "initials": "C", "orcid": "0000-0002-7141-4185", "researcher": {"href": "https://publications.scilifelab.se/researcher/dc67028bf0c04f1b9a73bac5e72f9897.json"}}, {"family": "Costello", "given": "Daniel J", "initials": "DJ", "orcid": "0000-0001-6023-8246", "researcher": {"href": "https://publications.scilifelab.se/researcher/07dfb1d34e394b07bf029fe1cfff028f.json"}}, {"family": "Bermingham", "given": "Niamh", "initials": "N"}, {"family": "Oldfors", "given": "Anders", "initials": "A", "orcid": "0000-0002-5758-7397", "researcher": {"href": "https://publications.scilifelab.se/researcher/e82034663f6647cd9827871bfca633ef.json"}}], "type": "journal article", "published": "2024-06-00", "journal": {"title": "Neuropathol Appl Neurobiol", "issn": "1365-2990", "volume": "50", "issue": "3", "pages": "e12995", "issn-l": null}, "abstract": "Polyglucosan storage disorders represent an emerging field within neurodegenerative and neuromuscular conditions, including Lafora disease (EPM2A, EPM2B), adult polyglucosan body disease (APBD, GBE1), polyglucosan body myopathies associated with RBCK1 deficiency (PGBM1, RBCK1) or glycogenin-1 deficiency (PGBM2, GYG1). While the storage material primarily comprises glycans, this study aimed to gain deeper insights into the protein components by proteomic profiling of the storage material in glycogenin-1 deficiency.\n\nWe employed molecular genetic analyses, quantitative mass spectrometry of laser micro-dissected polyglucosan bodies and muscle homogenate, immunohistochemistry and western blot analyses in muscle tissue from a 45-year-old patient with proximal muscle weakness from late teenage years due to polyglucosan storage myopathy.\n\nThe muscle tissue exhibited a complete absence of glycogenin-1 due to a novel homozygous deep intronic variant in GYG1 (c.7+992T>G), introducing a pseudo-exon causing frameshift and a premature stop codon. Accumulated proteins in the polyglucosan bodies constituted components of glycogen metabolism, protein quality control pathways and desmin. Muscle fibres containing polyglucosan bodies frequently exhibited depletion of normal glycogen.\n\nThe absence of glycogenin-1, a protein important for glycogen synthesis initiation, causes storage of polyglucosan that displays accumulation of several proteins, including those essential for glycogen synthesis, sequestosome 1/p62 and desmin, mirroring findings in RBCK1 deficiency. These results suggest shared pathogenic pathways across different diseases exhibiting polyglucosan storage. Such insights have implications for therapy in these rare yet devastating and presently untreatable disorders.", "doi": "10.1111/nan.12995", "pmid": "38923610", "labels": {"Clinical Genomics Gothenburg": "Service", "Integrated Microscopy Technologies Gothenburg": "Service", "Glycoproteomics and MS Proteomics": "Service", "Clinical Genomics": "Service"}, "xrefs": [], "notes": [], "created": "2024-11-01T08:17:11.069Z", "modified": "2024-11-27T15:36:56.743Z"}, {"entity": "publication", "iuid": "0f6972e45c1f4786b2da75f6dcc26197", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0f6972e45c1f4786b2da75f6dcc26197.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0f6972e45c1f4786b2da75f6dcc26197"}}, "title": "Exploring carbon source related localization and phosphorylation in the Snf1/Mig1 network using population and single cell-based approaches.", "authors": [{"family": "Braam", "given": "Svenja", "initials": "S"}, {"family": "Tripodi", "given": "Farida", "initials": "F"}, {"family": "\u00d6sterberg", "given": "Linnea", "initials": "L"}, {"family": "Persson", "given": "Sebastian", "initials": "S"}, {"family": "Welkenhuysen", "given": "Niek", "initials": "N"}, {"family": "Coccetti", "given": "Paola", "initials": "P"}, {"family": "Cvijovic", "given": "Marija", "initials": "M"}], "type": "journal article", "published": "2024-05-16", "journal": {"title": "Microb Cell", "issn": "2311-2638", "volume": "11", "pages": "143-154", "issn-l": null}, "abstract": "The AMPK/SNF1 pathway governs energy balance in eukaryotic cells, notably influencing glucose de-repression. In S. cerevisiae, Snf1 is phosphorylated and hence activated upon glucose depletion. This activation is required but is not sufficient for mediating glucose de-repression, indicating further glucose-dependent regulation mechanisms. Employing fluorescence recovery after photobleaching (FRAP) in conjunction with non-linear mixed effects modelling, we explore the spatial dynamics of Snf1 as well as the relationship between Snf1 phosphorylation and its target Mig1 controlled by hexose sugars. Our results suggest that inactivation of Snf1 modulates Mig1 localization and that the kinetic of Snf1 localization to the nucleus is modulated by the presence of non-fermentable carbon sources. Our data offer insight into the true complexity of regulation of this central signaling pathway in orchestrating cellular responses to fluctuating environmental cues. These insights not only expand our understanding of glucose homeostasis but also pave the way for further studies evaluating the importance of Snf1 localization in relation to its phosphorylation state and regulation of downstream targets.", "doi": "10.15698/mic2024.05.822", "pmid": "38756204", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11097897"}], "notes": [], "created": "2024-11-15T12:01:29.576Z", "modified": "2024-11-15T12:01:29.604Z"}, {"entity": "publication", "iuid": "e2e453cf6e8f4cdba5b424821324021d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e2e453cf6e8f4cdba5b424821324021d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e2e453cf6e8f4cdba5b424821324021d"}}, "title": "All-photonic kinase inhibitors: light-controlled release-and-report inhibition.", "authors": [{"family": "Fleming", "given": "Cassandra L", "initials": "CL", "orcid": "0000-0002-7730-7305", "researcher": {"href": "https://publications.scilifelab.se/researcher/a29a83ba2b3444768821489dc667279e.json"}}, {"family": "Benitez-Martin", "given": "Carlos", "initials": "C", "orcid": "0000-0003-1821-9388", "researcher": {"href": "https://publications.scilifelab.se/researcher/d1fcdd6e053b462998fe7f463be60d96.json"}}, {"family": "Bernson", "given": "Elin", "initials": "E", "orcid": "0000-0001-6414-5725", "researcher": {"href": "https://publications.scilifelab.se/researcher/ced3ddbde2ad4f28b28b622d817b2e59.json"}}, {"family": "Xu", "given": "Yongjin", "initials": "Y"}, {"family": "Kristenson", "given": "Linnea", "initials": "L"}, {"family": "Inghardt", "given": "Tord", "initials": "T", "orcid": "0000-0002-4804-9474", "researcher": {"href": "https://publications.scilifelab.se/researcher/bc8a41790a034fe48cce02c8e7034e34.json"}}, {"family": "Lundb\u00e4ck", "given": "Thomas", "initials": "T", "orcid": "0000-0002-8145-7808", "researcher": {"href": "https://publications.scilifelab.se/researcher/e13df787cb884549bcf333aba4e6f010.json"}}, {"family": "Thor\u00e9n", "given": "Fredrik B", "initials": "FB", "orcid": "0000-0003-2167-7451", "researcher": {"href": "https://publications.scilifelab.se/researcher/6e8a4846c6f44c0793f4cb5d73b66de6.json"}}, {"family": "Gr\u00f8tli", "given": "Morten", "initials": "M", "orcid": "0000-0003-3621-4222", "researcher": {"href": "https://publications.scilifelab.se/researcher/764706606bcb4afba1150af332c0f124.json"}}, {"family": "Andr\u00e9asson", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4695-7943", "researcher": {"href": "https://publications.scilifelab.se/researcher/28eb5affb5664c54be9171dfce6bea15.json"}}], "type": "journal article", "published": "2024-05-08", "journal": {"title": "Chem. Sci.", "issn": "2041-6520", "volume": "15", "issue": "18", "pages": "6897-6905", "issn-l": null}, "abstract": "Light-responsive molecular tools targeting kinases affords one the opportunity to study the underlying cellular function of selected kinases. In efforts to externally control lymphocyte-specific protein tyrosine kinase (LCK) activity, the development of release-and-report LCK inhibitors is described, in which (i) the release of the active kinase inhibitor can be controlled externally with light; and (ii) fluorescence is employed to report both the release and binding of the active kinase inhibitor. This introduces an unprecedented all-photonic method for users to both control and monitor real-time inhibitory activity. A functional cellular assay demonstrated light-mediated LCK inhibition in natural killer cells. The use of coumarin-derived caging groups resulted in rapid cellular uptake and non-specific intracellular localisation, while a BODIPY-derived caging group predominately localised in the cellular membrane. This concept of release-and-report inhibitors has the potential to be extended to other biorelevant targets where both spatiotemporal control in a cellular setting and a reporting mechanism would be beneficial.", "doi": "10.1039/d4sc00390j", "pmid": "38725520", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11077529"}, {"db": "pii", "key": "d4sc00390j"}], "notes": [], "created": "2024-11-15T12:04:25.342Z", "modified": "2024-11-15T12:04:25.556Z"}, {"entity": "publication", "iuid": "63f20378cd4741319b7a554d5c367300", "links": {"self": {"href": "https://publications.scilifelab.se/publication/63f20378cd4741319b7a554d5c367300.json"}, "display": {"href": "https://publications.scilifelab.se/publication/63f20378cd4741319b7a554d5c367300"}}, "title": "Amperometry and Electron Microscopy show Stress Granules Induce Homotypic Fusion of Catecholamine Vesicles.", "authors": [{"family": "Gu", "given": "Hui", "initials": "H"}, {"family": "Gu", "given": "Chaoyi", "initials": "C"}, {"family": "Locker", "given": "Nicolas", "initials": "N"}, {"family": "Ewing", "given": "Andrew G", "initials": "AG", "orcid": "0000-0002-2084-0133", "researcher": {"href": "https://publications.scilifelab.se/researcher/c6ecb82dc7a6423fa0876822f5568e1b.json"}}], "type": "journal article", "published": "2024-04-15", "journal": {"title": "Angew. Chem. Int. Ed. Engl.", "issn": "1521-3773", "volume": "63", "issue": "16", "pages": "e202400422", "issn-l": "1433-7851"}, "abstract": "An overreactive stress granule (SG) pathway and long-lived, stable SGs formation are thought to participate in the progress of neurodegenerative diseases (NDs). To understand if and how SGs contribute to disorders of neurotransmitter release in NDs, we examined the interaction between extracellular isolated SGs and vesicles. Amperometry shows that the vesicular content increases and dynamics of vesicle opening slow down after vesicles are treated with SGs, suggesting larger vesicles are formed. Data from transmission electron microscopy (TEM) clearly shows that a portion of large dense-core vesicles (LDCVs) with double/multiple cores appear, thus confirming that SGs induce homotypic fusion between LDCVs. This might be a protective step to help cells to survive following high oxidative stress. A hypothetical mechanism is proposed whereby enriched mRNA or protein in the shell of SGs is likely to bind intrinsically disordered protein (IDP) regions of vesicle associated membrane protein (VAMP) driving a disrupted membrane between two closely buddled vesicles to fuse with each other to form double-core vesicles. Our results show that SGs induce homotypic fusion of LDCVs, providing better understanding of how SGs intervene in pathological processes and opening a new direction to investigations of SGs involved neurodegenerative disease.", "doi": "10.1002/anie.202400422", "pmid": "38380500", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2024-11-15T12:05:33.825Z", "modified": "2024-11-15T12:05:33.840Z"}, {"entity": "publication", "iuid": "46dfe0f573d5449e90d91f09b8e4c4b2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/46dfe0f573d5449e90d91f09b8e4c4b2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/46dfe0f573d5449e90d91f09b8e4c4b2"}}, "title": "Extracellular vesicles isolated from frozen and fresh human melanoma tissue are similar in purity and protein composition", "authors": [{"family": "D\u2019Arrigo", "given": "Daniele", "initials": "D"}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C", "orcid": "0000-0003-1279-1746", "researcher": {"href": "https://publications.scilifelab.se/researcher/e14e17d2cdb24a9f93991d83811c78b9.json"}}, {"family": "Urz\u00ec", "given": "Ornella", "initials": "O"}, {"family": "Park", "given": "Kyong Su", "initials": "KS", "orcid": "0000-0003-0902-7800", "researcher": {"href": "https://publications.scilifelab.se/researcher/26e308b29fe144b49f4db27f4b819c18.json"}}, {"family": "Bagge", "given": "Roger Olofsson", "initials": "RO"}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J", "orcid": "0000-0001-9195-9249", "researcher": {"href": "https://publications.scilifelab.se/researcher/0cbcaf6b5698411c92e0de9e8fcf390f.json"}}, {"family": "Crescitelli", "given": "Rossella", "initials": "R", "orcid": "0000-0002-1714-3169", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d4b955f26ca4a679deb090e30d0ccf1.json"}}], "type": "posted-content", "published": "2024-04-04", "journal": {"title": "biorxiv", "issn": null, "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": null, "doi": "10.1101/2024.04.03.587936", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2024-11-15T12:03:52.819Z", "modified": "2025-12-18T19:28:19.475Z"}, {"entity": "publication", "iuid": "117093123bac4845a3e4ddfe5763f423", "links": {"self": {"href": "https://publications.scilifelab.se/publication/117093123bac4845a3e4ddfe5763f423.json"}, "display": {"href": "https://publications.scilifelab.se/publication/117093123bac4845a3e4ddfe5763f423"}}, "title": "Viridibacillus culture derived silver nanoparticles exert potent anticancer action in 2D and 3D models of lung cancer via mitochondrial depolarization-mediated apoptosis.", "authors": [{"family": "Joshi", "given": "Abhayraj S", "initials": "AS"}, {"family": "Bapat", "given": "Mugdha V", "initials": "MV"}, {"family": "Singh", "given": "Priyanka", "initials": "P"}, {"family": "Mijakovic", "given": "Ivan", "initials": "I"}], "type": "journal article", "published": "2024-04-00", "journal": {"title": "Mater Today Bio", "issn": "2590-0064", "volume": "25", "pages": "100997", "issn-l": null}, "abstract": "Lung cancer is one of the most commonly occurring cancer types that accounts for almost 2 million cases per year. Its resistance to anticancer drugs, failure of new molecules in clinical trials, severe side-effects of current treatments, and its recurrence limit the success of anticancer therapies. Nanotherapeutic agents offer several advantages over conventional anticancer therapies, including improved retention in tumors, specificity, and anticancer effects at lower concentrations, hence reducing the side-effects. Here, we have explored the anticancer activity of silver nanoparticles synthesized in Viridibacillus sp. enriched culture medium for the first time. Such green nanoparticles, synthesized by biological systems, are superior to chemically synthesized ones in terms of their environmental footprint and production cost, and have one crucial advantage of excellent stability owing to their biological corona. To assess anticancer activity of these nanoparticles, we used conventional 2D cultured A549 cells as well as 3D spheroids of A549 cells. In both models of lung cancer, our silver nanoparticles diminished cell proliferation, arrested DNA synthesis, and showed a dose dependent cytotoxic effect. The nanoparticles damaged the DNA and mitochondrial structures in both A549 cells and A549 spheroids, leading to mitochondrial depolarization and increased cell permeability. Low lethal median doses (LD50) for 2D cultured A549 cells (1 \u03bcg/ml) and for A549 spheroids (13 \u03bcg/ml) suggest that our nanoparticles are potent anticancer agents. We also developed in vitro tumor progression model and in vitro tumor size model using 3D spheroids to test anticancer potential of our nanoparticles which otherwise would require longer experimental duration along with large number of animals and trained personnel. In these models, our nanoparticles showed strong dose dependent anticancer activity. In case of in vitro tumor progression model, the A549 cells failed to form tight spheroidal mass and showed increased dead cell fraction since day 1 as compared to control. On the other hand, in case of in vitro tumor size model, the 4 and 8 \u03bcg/ml nanoparticle treatment led to reduction in spheroid size from 615 \u00b1 53 \u03bcm to 440 \u00b1 45 \u03bcm and 612 \u00b1 44 \u03bcm to 368 \u00b1 62 \u03bcm respectively, within the time span of 3 days post treatment. We believe that use of such novel experimental models offers excellent and fast alternative to in vivo studies, and to the best of our knowledge, this is the first report that gives proof-of-concept for use of such novel in vitro cancer models to test anticancer agents such as Viridibacilli culture derived silver nanoparticles. Based on our results, we propose that these nanoparticles offer an interesting alternative for anticancer therapies, especially if they can be combined with classical anticancer drugs.", "doi": "10.1016/j.mtbio.2024.100997", "pmid": "38379934", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10876681"}, {"db": "pii", "key": "S2590-0064(24)00056-5"}], "notes": [], "created": "2024-11-15T12:07:37.483Z", "modified": "2024-11-15T12:07:37.596Z"}, {"entity": "publication", "iuid": "ee9a001962ec4a4190c4ad3d7ea4e90e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ee9a001962ec4a4190c4ad3d7ea4e90e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ee9a001962ec4a4190c4ad3d7ea4e90e"}}, "title": "Novel ultrasensitive immunoassay for the selective quantification of tau oligomers and related soluble aggregates.", "authors": [{"family": "Islam", "given": "Tohidul", "initials": "T"}, {"family": "Kvartsberg", "given": "Hlin", "initials": "H"}, {"family": "Sehrawat", "given": "Anuradha", "initials": "A"}, {"family": "Kac", "given": "Przemys\u0142aw R", "initials": "PR"}, {"family": "Becker", "given": "Bruno", "initials": "B"}, {"family": "Olsson", "given": "Maria", "initials": "M"}, {"family": "Abrahamson", "given": "Eric E", "initials": "EE"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H"}, {"family": "Ikonomovic", "given": "Milos D", "initials": "MD"}, {"family": "Blennow", "given": "Kaj", "initials": "K"}, {"family": "Karikari", "given": "Thomas K", "initials": "TK", "orcid": "0000-0003-1422-4358", "researcher": {"href": "https://publications.scilifelab.se/researcher/cf3831a3e6a341f4b0a728e591de5b42.json"}}], "type": "journal article", "published": "2024-04-00", "journal": {"title": "Alzheimers Dement", "issn": "1552-5279", "volume": "20", "issue": "4", "pages": "2894-2905", "issn-l": null}, "abstract": "Tau aggregation into paired helical filaments and neurofibrillary tangles is characteristic of Alzheimer's disease (AD) and related disorders. However, biochemical assays for the quantification of soluble, earlier-stage tau aggregates are lacking. We describe an immunoassay that is selective for tau oligomers and related soluble aggregates over monomers.\n\nA homogeneous (single-antibody) immunoassay was developed using a novel anti-tau monoclonal antibody and validated with recombinant and brain tissue-derived tau.\n\nThe assay signals were concentration dependent for recombinant tau aggregates in solution but not monomers, and recognized peptides within, but not outside, the aggregation-prone microtubule binding region. The signals in inferior and middle frontal cortical tissue homogenates increased with neuropathologically determined Braak staging, and were higher in insoluble than soluble homogenized brain fractions. Autopsy-verified AD gave stronger signals than other neurodegenerative diseases.\n\nThe quantitative oligomer/soluble aggregate-specific assay can identify soluble tau aggregates, including oligomers, from monomers in human and in vitro biospecimens.\n\nThe aggregation of tau to form fibrils and neurofibrillary tangles is a key feature of Alzheimer's disease. However, biochemical assays for the quantification of oligomers/soluble aggregated forms of tau are lacking. We developed a new assay that preferentially binds to soluble tau aggregates, including oligomers and fibrils, versus monomers. The assay signal increased corresponding to the total protein content, Braak staging, and insolubility of the sequentially homogenized brain tissue fractions in an autopsy-verified cohort. The assay recognized tau peptides containing the microtubule binding region but not those covering the N- or C-terminal regions only.", "doi": "10.1002/alz.13711", "pmid": "38520322", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11032517"}], "notes": [], "created": "2024-11-15T12:06:39.561Z", "modified": "2024-11-15T12:06:39.616Z"}, {"entity": "publication", "iuid": "fbfe8d946e954dbba3307c6829554950", "links": {"self": {"href": "https://publications.scilifelab.se/publication/fbfe8d946e954dbba3307c6829554950.json"}, "display": {"href": "https://publications.scilifelab.se/publication/fbfe8d946e954dbba3307c6829554950"}}, "title": "Liprin-\u03b1 proteins are master regulators of human presynapse assembly.", "authors": [{"family": "Marc\u00f3 de la Cruz", "given": "Berta", "initials": "B", "orcid": "0009-0003-5209-6577", "researcher": {"href": "https://publications.scilifelab.se/researcher/d07a1af5c733449aa1d23d5bacea0a0a.json"}}, {"family": "Campos", "given": "Joaqu\u00edn", "initials": "J"}, {"family": "Molinaro", "given": "Angela", "initials": "A"}, {"family": "Xie", "given": "Xingqiao", "initials": "X"}, {"family": "Jin", "given": "Gaowei", "initials": "G"}, {"family": "Wei", "given": "Zhiyi", "initials": "Z", "orcid": "0000-0002-4446-6502", "researcher": {"href": "https://publications.scilifelab.se/researcher/806839d03f6f436496b68c4951a646c7.json"}}, {"family": "Acuna", "given": "Claudio", "initials": "C", "orcid": "0000-0002-8849-6260", "researcher": {"href": "https://publications.scilifelab.se/researcher/a0a8c8497ca744b9a1c6cf683b515482.json"}}, {"family": "Sterky", "given": "Fredrik H", "initials": "FH", "orcid": "0000-0001-8881-0523", "researcher": {"href": "https://publications.scilifelab.se/researcher/c882670f832e4412869ab7667b115a81.json"}}], "type": "journal article", "published": "2024-04-00", "journal": {"title": "Nat. Neurosci.", "issn": "1546-1726", "volume": "27", "issue": "4", "pages": "629-642", "issn-l": "1097-6256"}, "abstract": "The formation of mammalian synapses entails the precise alignment of presynaptic release sites with postsynaptic receptors but how nascent cell-cell contacts translate into assembly of presynaptic specializations remains unclear. Guided by pioneering work in invertebrates, we hypothesized that in mammalian synapses, liprin-\u03b1 proteins directly link trans-synaptic initial contacts to downstream steps. Here we show that, in human neurons lacking all four liprin-\u03b1 isoforms, nascent synaptic contacts are formed but recruitment of active zone components and accumulation of synaptic vesicles is blocked, resulting in 'empty' boutons and loss of synaptic transmission. Interactions with presynaptic cell adhesion molecules of either the LAR-RPTP family or neurexins via CASK are required to localize liprin-\u03b1 to nascent synaptic sites. Liprin-\u03b1 subsequently recruits presynaptic components via a direct interaction with ELKS proteins. Thus, assembly of human presynaptic terminals is governed by a hierarchical sequence of events in which the recruitment of liprin-\u03b1 proteins by presynaptic cell adhesion molecules is a critical initial step.", "doi": "10.1038/s41593-024-01592-9", "pmid": "38472649", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11001580"}, {"db": "pii", "key": "10.1038/s41593-024-01592-9"}], "notes": [], "created": "2024-11-15T12:09:10.518Z", "modified": "2024-11-15T12:09:10.986Z"}, {"entity": "publication", "iuid": "bb5b88a1f4ca4a78a7b60c025b82180b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bb5b88a1f4ca4a78a7b60c025b82180b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bb5b88a1f4ca4a78a7b60c025b82180b"}}, "title": "Multimodal bioimaging across disciplines and scales: challenges, opportunities and breaking down barriers", "authors": [{"family": "Bischof", "given": "Johanna", "initials": "J", "orcid": "0000-0002-5668-841X", "researcher": {"href": "https://publications.scilifelab.se/researcher/99ccae56fae9424a99b47695cfb5aae2.json"}}, {"family": "Fletcher", "given": "Georgina", "initials": "G"}, {"family": "Verkade", "given": "Paul", "initials": "P"}, {"family": "Kuntner", "given": "Claudia", "initials": "C"}, {"family": "Fernandez-Rodriguez", "given": "Julia", "initials": "J", "orcid": "0000-0003-4522-0966", "researcher": {"href": "https://publications.scilifelab.se/researcher/3bd9c743e99d479cb752aeec947acab3.json"}}, {"family": "Chaabane", "given": "Linda", "initials": "L"}, {"family": "Rose", "given": "Leor Ariel", "initials": "LA"}, {"family": "Walter", "given": "Andreas", "initials": "A"}, {"family": "Vandenbosch", "given": "Michiel", "initials": "M"}, {"family": "van Zandvoort", "given": "Marc A M J", "initials": "MAMJ"}, {"family": "Zaritsky", "given": "Assaf", "initials": "A"}, {"family": "Keppler", "given": "Antje", "initials": "A"}, {"family": "Parsons", "given": "Maddy", "initials": "M"}], "type": "journal-article", "published": "2024-03-01", "journal": {"title": "npj Imaging", "issn": "2948-197X", "volume": "2", "issue": "1", "pages": "5", "issn-l": null}, "abstract": "Multimodal bioimaging is a broad term used to describe experimental workflows that employ two or more different imaging modalities. Such approaches have been in use across life science domains for several years but these remain relatively limited in scope, in part due to the complexity of undertaking these types of analysis. Expanding these workflows to encompass diverse, emerging technology holds potential to revolutionize our understanding of spatial biology. In this perspective we reflect on the instrument and workflows in current use, emerging areas to consider and our experience of the barriers to broader adoption and progress. We propose several enabling solutions across the different challenge areas, emerging opportunities for consideration and highlight some of the key community activities to help move the field forward.", "doi": "10.1038/s44303-024-00010-w", "pmid": "40603654", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC12118647"}, {"db": "pii", "key": "10.1038/s44303-024-00010-w"}], "notes": [], "created": "2024-11-15T12:01:08.483Z", "modified": "2025-12-04T19:31:13.865Z"}, {"entity": "publication", "iuid": "c441c9fef76f49a88b532d22fe3c3d1f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c441c9fef76f49a88b532d22fe3c3d1f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c441c9fef76f49a88b532d22fe3c3d1f"}}, "title": "Subcellular protein turnover in human neural progenitor cells revealed by correlative electron microscopy and nanoscale secondary ion mass spectrometry imaging.", "authors": [{"family": "Lork", "given": "Alicia A", "initials": "AA", "orcid": "0000-0001-6718-7146", "researcher": {"href": "https://publications.scilifelab.se/researcher/c1fd9628a0dc4c12a20dd58f9ab3a3be.json"}}, {"family": "Rabasco", "given": "Stefania", "initials": "S"}, {"family": "Ernst", "given": "Carl", "initials": "C"}, {"family": "du Toit", "given": "Andr\u00e9", "initials": "A"}, {"family": "Rizzoli", "given": "Silvio O", "initials": "SO", "orcid": "0000-0002-1667-7839", "researcher": {"href": "https://publications.scilifelab.se/researcher/ac3aa5d48eb9402fa8da3c921f86c418.json"}}, {"family": "Phan", "given": "Nhu T N", "initials": "NTN", "orcid": "0000-0002-3576-0494", "researcher": {"href": "https://publications.scilifelab.se/researcher/6fa50d61430943a6af068ef05736ea4a.json"}}], "type": "journal article", "published": "2024-02-28", "journal": {"title": "Chem. Sci.", "issn": "2041-6520", "volume": "15", "issue": "9", "pages": "3311-3322", "issn-l": null}, "abstract": "Protein turnover is a critical process for accurate cellular function, in which damaged proteins in the cells are gradually replaced with newly synthesized ones. Many previous studies on cellular protein turnover have used stable isotopic labelling by amino acids in cell culture (SILAC), followed by proteomic bulk analysis. However, this approach does not take into account the heterogeneity observed at the single-cell and subcellular levels. To address this, we investigated the protein turnover of neural progenitor cells at the subcellular resolution, using correlative TEM and NanoSIMS imaging, relying on a pulse-chase analysis of isotopically-labelled protein precusors. Cellular protein turnover was found significantly heterogenous across individual organelles, which indicates a possible relation between protein turnover and subcellular activity. In addition, different isotopically-labelled amino acids provided different turnover patterns, in spite of all being protein precursors, suggesting that they undergo distinct protein synthesis and metabolic pathways at the subcellular level.", "doi": "10.1039/d3sc05629e", "pmid": "38425528", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10901485"}, {"db": "pii", "key": "d3sc05629e"}], "notes": [], "created": "2024-11-15T12:08:18.202Z", "modified": "2024-11-15T12:08:18.566Z"}, {"entity": "publication", "iuid": "3778dd8279784fbfb3ef2e0fe7ceb521", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3778dd8279784fbfb3ef2e0fe7ceb521.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3778dd8279784fbfb3ef2e0fe7ceb521"}}, "title": "Spatial Neurolipidomics at the Single Amyloid-\u03b2 Plaque Level in Postmortem Human Alzheimer's Disease Brain.", "authors": [{"family": "Michno", "given": "Wojciech", "initials": "W"}, {"family": "Bowman", "given": "Andrew", "initials": "A"}, {"family": "Jha", "given": "Durga", "initials": "D"}, {"family": "Minta", "given": "Karolina", "initials": "K"}, {"family": "Ge", "given": "Junyue", "initials": "J"}, {"family": "Koutarapu", "given": "Srinivas", "initials": "S"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H"}, {"family": "Blennow", "given": "Kaj", "initials": "K"}, {"family": "Lashley", "given": "Tammaryn", "initials": "T"}, {"family": "Heeren", "given": "Ron M A", "initials": "RMA", "orcid": "0000-0002-6533-7179", "researcher": {"href": "https://publications.scilifelab.se/researcher/2e7bc52c5d4848aabb62bde4932efa1a.json"}}, {"family": "Hanrieder", "given": "J\u00f6rg", "initials": "J", "orcid": "0000-0001-6059-198X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e65454100674f98bf8f2575093f2441.json"}}], "type": "journal article", "published": "2024-02-21", "journal": {"title": "ACS Chem Neurosci", "issn": "1948-7193", "volume": "15", "issue": "4", "pages": "877-888", "issn-l": "1948-7193"}, "abstract": "Lipid dysregulations have been critically implicated in Alzheimer's disease (AD) pathology. Chemical analysis of amyloid-\u03b2 (A\u03b2) plaque pathology in transgenic AD mouse models has demonstrated alterations in the microenvironment in the direct proximity of A\u03b2 plaque pathology. In mouse studies, differences in lipid patterns linked to structural polymorphism among A\u03b2 pathology, such as diffuse, immature, and mature fibrillary aggregates, have also been reported. To date, no comprehensive analysis of neuronal lipid microenvironment changes in human AD tissue has been performed. Here, for the first time, we leverage matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) through a high-speed and spatial resolution commercial time-of-light instrument, as well as a high-mass-resolution in-house-developed orbitrap system to characterize the lipid microenvironment in postmortem human brain tissue from AD patients carrying Presenilin 1 mutations (PSEN1) that lead to familial forms of AD (fAD). Interrogation of the spatially resolved MSI data on a single A\u03b2 plaque allowed us to verify nearly 40 sphingolipid and phospholipid species from diverse subclasses being enriched and depleted, in relation to the A\u03b2 deposits. This included monosialo-gangliosides (GM), ceramide monohexosides (HexCer), ceramide-1-phosphates (CerP), ceramide phosphoethanolamine conjugates (PE-Cer), sulfatides (ST), as well as phosphatidylinositols (PI), phosphatidylethanolamines (PE), and phosphatidic acid (PA) species (including Lyso-forms). Indeed, many of the sphingolipid species overlap with the species previously seen in transgenic AD mouse models. Interestingly, in comparison to the animal studies, we observed an increased level of localization of PE and PI species containing arachidonic acid (AA). These findings are highly relevant, demonstrating for the first time A\u03b2 plaque pathology-related alteration in the lipid microenvironment in humans. They provide a basis for the development of potential lipid biomarkers for AD characterization and insight into human-specific molecular pathway alterations.", "doi": "10.1021/acschemneuro.4c00006", "pmid": "38299453", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10885149"}], "notes": [], "created": "2024-11-15T12:09:25.953Z", "modified": "2024-11-15T12:09:26.134Z"}, {"entity": "publication", "iuid": "7a8969678e1742c5b58d335eda1d3b55", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7a8969678e1742c5b58d335eda1d3b55.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7a8969678e1742c5b58d335eda1d3b55"}}, "title": "Omega-3 and -6 Fatty Acids Alter the Membrane Lipid Composition and Vesicle Size to Regulate Exocytosis and Storage of Catecholamines.", "authors": [{"family": "Gu", "given": "Chaoyi", "initials": "C"}, {"family": "Philipsen", "given": "Mai H", "initials": "MH"}, {"family": "Ewing", "given": "Andrew G", "initials": "AG", "orcid": "0000-0002-2084-0133", "researcher": {"href": "https://publications.scilifelab.se/researcher/c6ecb82dc7a6423fa0876822f5568e1b.json"}}], "type": "journal article", "published": "2024-02-21", "journal": {"title": "ACS Chem Neurosci", "issn": "1948-7193", "volume": "15", "issue": "4", "pages": "816-826", "issn-l": "1948-7193"}, "abstract": "The two essential fatty acids, alpha-linolenic acid and linoleic acid, and the higher unsaturated fatty acids synthesized from them are critical for the development and maintenance of normal brain functions. Deficiencies of these fatty acids have been shown to cause damage to the neuronal development, cognition, and locomotor function. We combined electrochemistry and imaging techniques to examine the effects of the two essential fatty acids on catecholamine release dynamics and the vesicle content as well as on the cell membrane phospholipid composition to understand how they impact exocytosis and by extension neurotransmission at the single-cell level. Incubation of either of the two fatty acids reduces the size of secretory vesicles and enables the incorporation of more double bonds into the cell membrane structure, resulting in higher membrane flexibility. This subsequently affects proteins regulating the dynamics of the exocytotic fusion pore and thereby affects exocytosis. Our data suggest a possible pathway whereby the two essential fatty acids affect the membrane structure to impact exocytosis and provide a potential treatment for diseases and impairments related to catecholamine signaling.", "doi": "10.1021/acschemneuro.3c00741", "pmid": "38344810", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10884999"}], "notes": [], "created": "2024-11-15T12:05:20.148Z", "modified": "2024-11-15T12:05:20.159Z"}, {"entity": "publication", "iuid": "2085b9fd009043b9976ccdc98189fe21", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2085b9fd009043b9976ccdc98189fe21.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2085b9fd009043b9976ccdc98189fe21"}}, "title": "Proteomic profiling of tumour tissue-derived extracellular vesicles in colon cancer.", "authors": [{"family": "Cvjetkovic", "given": "Aleksander", "initials": "A", "orcid": "0000-0002-9131-9791", "researcher": {"href": "https://publications.scilifelab.se/researcher/166451e5c8e54c0da297f6238c42c334.json"}}, {"family": "Karimi", "given": "Nasibeh", "initials": "N"}, {"family": "Crescitelli", "given": "Rossella", "initials": "R", "orcid": "0000-0002-1714-3169", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d4b955f26ca4a679deb090e30d0ccf1.json"}}, {"family": "Thorsell", "given": "Annika", "initials": "A"}, {"family": "Taflin", "given": "Helena", "initials": "H"}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C"}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J", "orcid": "0000-0001-9195-9249", "researcher": {"href": "https://publications.scilifelab.se/researcher/0cbcaf6b5698411c92e0de9e8fcf390f.json"}}], "type": "journal article", "published": "2024-02-00", "journal": {"title": "J Extracell Biol", "issn": "2768-2811", "volume": "3", "issue": "2", "pages": "e127", "issn-l": null}, "abstract": "Colon cancer is one of the most commonly occurring tumours among both women and men, and over the past decades the incidence has been on the rise. As such, the need for biomarker identification as well as an understanding of the underlying disease mechanism has never been greater. Extracellular vesicles are integral mediators of cell-to-cell communication and offer a unique opportunity to study the machinery that drives disease progression, and they also function as vectors for potential biomarkers. Tumour tissue and healthy mucosal tissue from the colons of ten patients were used to isolate tissue-resident EVs that were subsequently subjected to global quantitative proteomic analysis through LC-MS/MS. In total, more than 2000 proteins were identified, with most of the common EV markers being among them. Bioinformatics revealed a clear underrepresentation of proteins involved in energy production and cellular adhesion in tumour EVs, while proteins involved in protein biosynthesis were overrepresented. Additionally, 53 membrane proteins were found to be significantly upregulated in tumour EVs. Among them were several proteins with enzymatic functions that degrade the extracellular matrix, and three of these, Fibroblast activating factor (FAP), Cell surface hyaluronidase (CEMIP2), as well as Ephrin receptor B3 (EPHB3), were validated and found to be consistent with the global quantitative results. These stark differences in the proteomes between healthy and cancerous tissue emphasise the importance of the interstitial vesicle secretome as a major player of disease development.", "doi": "10.1002/jex2.127", "pmid": "38939898", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service", "Glycoproteomics and MS Proteomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC11080707"}, {"db": "pii", "key": "JEX2127"}], "notes": [], "created": "2024-11-15T12:03:23.005Z", "modified": "2025-10-23T09:23:07.521Z"}, {"entity": "publication", "iuid": "7294a8cd879d4bff8d66b35a02dd1512", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7294a8cd879d4bff8d66b35a02dd1512.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7294a8cd879d4bff8d66b35a02dd1512"}}, "title": "Community-developed checklists for publishing images and image analyses.", "authors": [{"family": "Schmied", "given": "Christopher", "initials": "C", "orcid": "0000-0003-2058-1124", "researcher": {"href": "https://publications.scilifelab.se/researcher/ad6aa8681f944fccbc57141cfcebfcc6.json"}}, {"family": "Nelson", "given": "Michael S", "initials": "MS", "orcid": "0000-0003-0480-5597", "researcher": {"href": "https://publications.scilifelab.se/researcher/3897b6add2a340e19ad1e051f08931c5.json"}}, {"family": "Avilov", "given": "Sergiy", "initials": "S", "orcid": "0000-0003-0860-8857", "researcher": {"href": "https://publications.scilifelab.se/researcher/25497ef7230445d9a65ff80f2bd3caa9.json"}}, {"family": "Bakker", "given": "Gert-Jan", "initials": "GJ", "orcid": "0000-0003-3602-0014", "researcher": {"href": "https://publications.scilifelab.se/researcher/00acada708a34d5c8414acc61acad548.json"}}, {"family": "Bertocchi", "given": "Cristina", "initials": "C", "orcid": "0000-0003-0907-1318", "researcher": {"href": "https://publications.scilifelab.se/researcher/c0570143267045ed89697ade5036cca9.json"}}, {"family": "Bischof", "given": "Johanna", "initials": "J", "orcid": "0000-0002-5668-841X", "researcher": {"href": "https://publications.scilifelab.se/researcher/99ccae56fae9424a99b47695cfb5aae2.json"}}, {"family": "Boehm", "given": "Ulrike", "initials": "U", "orcid": "0000-0001-7471-2244", "researcher": {"href": "https://publications.scilifelab.se/researcher/4c8a69a74a1d4760a424493c109ca0c1.json"}}, {"family": "Brocher", "given": "Jan", "initials": "J", "orcid": "0000-0001-8565-625X", "researcher": {"href": "https://publications.scilifelab.se/researcher/ea740b88acb542c69caacb8f4c6e4ef5.json"}}, {"family": "Carvalho", "given": "Mariana T", "initials": "MT", "orcid": "0000-0002-4281-5799", "researcher": {"href": "https://publications.scilifelab.se/researcher/e83178e155c34acbbd2174b68c0caeee.json"}}, {"family": "Chiritescu", "given": "Catalin", "initials": "C"}, {"family": "Christopher", "given": "Jana", "initials": "J", "orcid": "0000-0002-2699-3368", "researcher": {"href": "https://publications.scilifelab.se/researcher/a4199233f0b5405db54bb4f9b284d4c4.json"}}, {"family": "Cimini", "given": "Beth A", "initials": "BA", "orcid": "0000-0001-9640-9318", "researcher": {"href": "https://publications.scilifelab.se/researcher/db23220ace18412a872eeedc98b6ca3d.json"}}, {"family": "Conde-Sousa", "given": "Eduardo", "initials": "E", "orcid": "0000-0002-6591-5063", "researcher": {"href": "https://publications.scilifelab.se/researcher/1a138d62e38846f09279e5e387d878ee.json"}}, {"family": "Ebner", "given": "Michael", "initials": "M", "orcid": "0000-0003-4234-7187", "researcher": {"href": "https://publications.scilifelab.se/researcher/61c1b15605954530a45728a1e3a16836.json"}}, {"family": "Ecker", "given": "Rupert", "initials": "R", "orcid": "0000-0002-1095-8592", "researcher": {"href": "https://publications.scilifelab.se/researcher/78afc9a321764db8a44fe0573291f6f5.json"}}, {"family": "Eliceiri", "given": "Kevin", "initials": "K", "orcid": "0000-0001-8678-670X", "researcher": {"href": "https://publications.scilifelab.se/researcher/acb896fcca6a49b096068c3b5294624d.json"}}, {"family": "Fernandez-Rodriguez", "given": "Julia", "initials": "J", "orcid": "0000-0003-4522-0966", "researcher": {"href": "https://publications.scilifelab.se/researcher/3bd9c743e99d479cb752aeec947acab3.json"}}, {"family": "Gaudreault", "given": "Nathalie", "initials": "N", "orcid": "0000-0002-9220-5366", "researcher": {"href": "https://publications.scilifelab.se/researcher/c2a75875451c4bb0ab0d96da9d52fd0d.json"}}, {"family": "Gelman", "given": "Laurent", "initials": "L", "orcid": "0000-0003-3277-3115", "researcher": {"href": "https://publications.scilifelab.se/researcher/879c0baa809c45caa6d67dffde4ecabd.json"}}, {"family": "Grunwald", "given": "David", "initials": "D", "orcid": "0000-0001-9067-804X", "researcher": {"href": "https://publications.scilifelab.se/researcher/b46507eeed044d7b9fdf394b0d396edd.json"}}, {"family": "Gu", "given": "Tingting", "initials": "T", "orcid": "0000-0002-0696-0008", "researcher": {"href": "https://publications.scilifelab.se/researcher/2776dd1980da4bad80080a257cba796b.json"}}, {"family": "Halidi", "given": "Nadia", "initials": "N", "orcid": "0000-0003-0613-2365", "researcher": {"href": "https://publications.scilifelab.se/researcher/9994a26aeda440e7b81825398f3c4839.json"}}, {"family": "Hammer", "given": "Mathias", "initials": "M", "orcid": "0000-0002-5771-5694", "researcher": {"href": "https://publications.scilifelab.se/researcher/50f30e1235c9490ea5eea47f9b45e447.json"}}, {"family": "Hartley", "given": "Matthew", "initials": "M", "orcid": "0000-0001-6178-2884", "researcher": {"href": "https://publications.scilifelab.se/researcher/61b701d8944f41d1ab1348b4a7745d06.json"}}, {"family": "Held", "given": "Marie", "initials": "M", "orcid": "0000-0003-0118-5898", "researcher": {"href": "https://publications.scilifelab.se/researcher/986a1649fbdb4c93a9480d000b3fed42.json"}}, {"family": "Jug", "given": "Florian", "initials": "F", "orcid": "0000-0002-8499-5812", "researcher": {"href": "https://publications.scilifelab.se/researcher/40ccce2be15f4d8fab6a75615ebc1246.json"}}, {"family": "Kapoor", "given": "Varun", "initials": "V"}, {"family": "Koksoy", "given": "Ayse Aslihan", "initials": "AA", "orcid": "0000-0003-3092-5410", "researcher": {"href": "https://publications.scilifelab.se/researcher/cbad4193d35348c9af4d0a1bb8021a6d.json"}}, {"family": "Lacoste", "given": "Judith", "initials": "J", "orcid": "0000-0002-8783-8599", "researcher": {"href": "https://publications.scilifelab.se/researcher/d910c1919e154367bffa2e67d0b014be.json"}}, {"family": "Le D\u00e9v\u00e9dec", "given": "Sylvia", "initials": "S", "orcid": "0000-0002-0615-9616", "researcher": {"href": "https://publications.scilifelab.se/researcher/52914a32566d411e8ef2d07605d8f1fc.json"}}, {"family": "Le Guyader", "given": "Sylvie", "initials": "S", "orcid": "0000-0002-8812-8046", "researcher": {"href": "https://publications.scilifelab.se/researcher/ab8ef030a1be4d659c4b66bef5c939d2.json"}}, {"family": "Liu", "given": "Penghuan", "initials": "P"}, {"family": "Martins", "given": "Gabriel G", "initials": "GG", "orcid": "0000-0002-6506-9776", "researcher": {"href": "https://publications.scilifelab.se/researcher/c04a08e246854401b529158afe9de318.json"}}, {"family": "Mathur", "given": "Aastha", "initials": "A", "orcid": "0000-0001-9734-9767", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ae033e0cc7a4b05b7a8ed203f60b90a.json"}}, {"family": "Miura", "given": "Kota", "initials": "K", "orcid": "0000-0001-6926-191X", "researcher": {"href": "https://publications.scilifelab.se/researcher/d2924dc08df743e188b5ead9a88449a6.json"}}, {"family": "Montero Llopis", "given": "Paula", "initials": "P", "orcid": "0000-0002-5983-2296", "researcher": {"href": "https://publications.scilifelab.se/researcher/9fb8e94dd08e4ca9aa6dad39c13ad963.json"}}, {"family": "Nitschke", "given": "Roland", "initials": "R"}, {"family": "North", "given": "Alison", "initials": "A"}, {"family": "Parslow", "given": "Adam C", "initials": "AC", "orcid": "0000-0002-9868-6914", "researcher": {"href": "https://publications.scilifelab.se/researcher/c96e876d9fde4543b3f1401cdeb78f91.json"}}, {"family": "Payne-Dwyer", "given": "Alex", "initials": "A", "orcid": "0000-0001-8802-352X", "researcher": {"href": "https://publications.scilifelab.se/researcher/719a8aba6ac2413bb571dbc252c3556d.json"}}, {"family": "Plantard", "given": "Laure", "initials": "L", "orcid": "0000-0002-8386-3535", "researcher": {"href": "https://publications.scilifelab.se/researcher/08f3d7e2b4fe461c878cadd35ddc0018.json"}}, {"family": "Ali", "given": "Rizwan", "initials": "R"}, {"family": "Schroth-Diez", "given": "Britta", "initials": "B"}, {"family": "Sch\u00fctz", "given": "Lucas", "initials": "L"}, {"family": "Scott", "given": "Ryan T", "initials": "RT", "orcid": "0000-0003-0654-5661", "researcher": {"href": "https://publications.scilifelab.se/researcher/66cf459366ef400a986a5ac8bc5a3558.json"}}, {"family": "Seitz", "given": "Arne", "initials": "A", "orcid": "0000-0002-5013-1557", "researcher": {"href": "https://publications.scilifelab.se/researcher/a22f2f49c174438a9c42e69ac6a451e8.json"}}, {"family": "Selchow", "given": "Olaf", "initials": "O", "orcid": "0009-0005-4110-9373", "researcher": {"href": "https://publications.scilifelab.se/researcher/6ca99855c87a4298b366c6faff96ddc9.json"}}, {"family": "Sharma", "given": "Ved P", "initials": "VP", "orcid": "0000-0001-9998-5070", "researcher": {"href": "https://publications.scilifelab.se/researcher/73bca36d466b426eb62b83ca3289c7f0.json"}}, {"family": "Spitaler", "given": "Martin", "initials": "M", "orcid": "0000-0002-8833-638X", "researcher": {"href": "https://publications.scilifelab.se/researcher/2bc5b8c26b044442b7c971043a57eded.json"}}, {"family": "Srinivasan", "given": "Sathya", "initials": "S", "orcid": "0000-0002-5386-8722", "researcher": {"href": "https://publications.scilifelab.se/researcher/b5f7cae0ad8e49b2a932ab22bf911fb6.json"}}, {"family": "Strambio-De-Castillia", "given": "Caterina", "initials": "C", "orcid": "0000-0002-1069-1816", "researcher": {"href": "https://publications.scilifelab.se/researcher/d56f91373ceb40bab6bae2635961bdf5.json"}}, {"family": "Taatjes", "given": "Douglas", "initials": "D", "orcid": "0000-0003-1903-983X", "researcher": {"href": "https://publications.scilifelab.se/researcher/c6ea5eaf638d44878c83087e2dded63a.json"}}, {"family": "Tischer", "given": "Christian", "initials": "C", "orcid": "0000-0003-4105-1990", "researcher": {"href": "https://publications.scilifelab.se/researcher/3dc57b68dd4e40d28414fec28783bcc4.json"}}, {"family": "Jambor", "given": "Helena Klara", "initials": "HK", "orcid": "0000-0003-3397-1842", "researcher": {"href": "https://publications.scilifelab.se/researcher/4d9c995274164d5298f59dbd5c088ab7.json"}}], "type": "journal article", "published": "2024-02-00", "journal": {"title": "Nat. Methods", "issn": "1548-7105", "volume": "21", "issue": "2", "pages": "170-181", "issn-l": "1548-7091"}, "abstract": "Images document scientific discoveries and are prevalent in modern biomedical research. Microscopy imaging in particular is currently undergoing rapid technological advancements. However, for scientists wishing to publish obtained images and image-analysis results, there are currently no unified guidelines for best practices. Consequently, microscopy images and image data in publications may be unclear or difficult to interpret. Here, we present community-developed checklists for preparing light microscopy images and describing image analyses for publications. These checklists offer authors, readers and publishers key recommendations for image formatting and annotation, color selection, data availability and reporting image-analysis workflows. The goal of our guidelines is to increase the clarity and reproducibility of image figures and thereby to heighten the quality and explanatory power of microscopy data.", "doi": "10.1038/s41592-023-01987-9", "pmid": "37710020", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "mid", "key": "NIHMS1934198"}, {"db": "pmc", "key": "PMC10922596"}, {"db": "pii", "key": "10.1038/s41592-023-01987-9"}], "notes": [], "created": "2023-12-01T10:54:11.960Z", "modified": "2024-11-15T12:11:05.874Z"}, {"entity": "publication", "iuid": "74c9798d35d94044948babcc62227983", "links": {"self": {"href": "https://publications.scilifelab.se/publication/74c9798d35d94044948babcc62227983.json"}, "display": {"href": "https://publications.scilifelab.se/publication/74c9798d35d94044948babcc62227983"}}, "title": "Astrocytic Regulation of Endocannabinoid-Dependent Synaptic Plasticity in the Dorsolateral Striatum.", "authors": [{"family": "Adermark", "given": "Louise", "initials": "L"}, {"family": "Stomberg", "given": "Rosita", "initials": "R"}, {"family": "S\u00f6derpalm", "given": "Bo", "initials": "B"}, {"family": "Ericson", "given": "Mia", "initials": "M", "orcid": "0000-0002-7557-7109", "researcher": {"href": "https://publications.scilifelab.se/researcher/5b639bcd6dc44459a8cf95ff214ce74d.json"}}], "type": "journal article", "published": "2024-01-01", "journal": {"title": "Int J Mol Sci", "issn": "1422-0067", "volume": "25", "issue": "1", "issn-l": null}, "abstract": "Astrocytes are pivotal for synaptic transmission and may also play a role in the induction and expression of synaptic plasticity, including endocannabinoid-mediated long-term depression (eCB-LTD). In the dorsolateral striatum (DLS), eCB signaling plays a major role in balancing excitation and inhibition and promoting habitual learning. The aim of this study was to outline the role of astrocytes in regulating eCB signaling in the DLS. To this end, we employed electrophysiological slice recordings combined with metabolic, chemogenetic and pharmacological approaches in an attempt to selectively suppress astrocyte function. High-frequency stimulation induced eCB-mediated LTD (HFS-LTD) in brain slices from both male and female rats. The metabolic uncoupler fluorocitrate (FC) reduced the probability of transmitter release and depressed synaptic output in a manner that was independent on cannabinoid 1 receptor (CB1R) activation. Fluorocitrate did not affect the LTD induced by the CB1R agonist WIN55,212-2, but enhanced CB1R-dependent HFS-LTD. Reduced neurotransmission and facilitated HFS-LTD were also observed during chemogenetic manipulation using Gi-coupled DREADDs targeting glial fibrillary acidic protein (GFAP)-expressing cells, during the pharmacological inhibition of connexins using carbenoxolone disodium, or during astrocytic glutamate uptake using TFB-TBOA. While pretreatment with the N-methyl-D-aspartate (NMDA) receptor antagonist 2-amino-5-phosphonopentanoic acid (APV) failed to prevent synaptic depression induced by FC, it blocked the facilitation of HFS-LTD. While the lack of tools to disentangle astrocytes from neurons is a major limitation of this study, our data collectively support a role for astrocytes in modulating basal neurotransmission and eCB-mediated synaptic plasticity.", "doi": "10.3390/ijms25010581", "pmid": "38203752", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10779090"}, {"db": "pii", "key": "ijms25010581"}], "notes": [], "created": "2024-11-15T12:00:49.810Z", "modified": "2024-11-15T12:00:49.862Z"}, {"entity": "publication", "iuid": "ef5d317eb95d48488766e1cec7105d31", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ef5d317eb95d48488766e1cec7105d31.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ef5d317eb95d48488766e1cec7105d31"}}, "title": "Heat inactivation of foetal bovine serum performed after EV-depletion influences the proteome of cell-derived extracellular vesicles.", "authors": [{"family": "Urz\u00ec", "given": "Ornella", "initials": "O"}, {"family": "Bergqvist", "given": "Markus", "initials": "M"}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C"}, {"family": "Moschetti", "given": "Marta", "initials": "M"}, {"family": "Johansson", "given": "Junko", "initials": "J"}, {"family": "D Arrigo", "given": "Daniele", "initials": "D"}, {"family": "Olofsson Bagge", "given": "Roger", "initials": "R"}, {"family": "Crescitelli", "given": "Rossella", "initials": "R", "orcid": "0000-0002-1714-3169", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d4b955f26ca4a679deb090e30d0ccf1.json"}}], "type": "journal article", "published": "2024-01-00", "journal": {"title": "J Extracell Vesicles", "issn": "2001-3078", "volume": "13", "issue": "1", "pages": "e12408", "issn-l": "2001-3078"}, "abstract": "The release of extracellular vesicles (EVs) in cell cultures as well as their molecular cargo can be influenced by cell culture conditions such as the presence of foetal bovine serum (FBS). Although several studies have evaluated the effect of removing FBS-derived EVs by ultracentrifugation (UC), less is known about the influence of FBS heat inactivation (HI) on the cell-derived EVs. To assess this, three protocols based on different combinations of EV depletion by UC and HI were evaluated, including FBS ultracentrifuged but not heat inactivated (no-HI FBS), FBS heat inactivated before EV depletion (HI-before EV-depl FBS), and FBS heat inactivated after EV depletion (HI-after EV-depl FBS). We isolated large (L-EVs) and small EVs (S-EVs) from FBS treated in the three different ways, and we found that the S-EV pellet from HI-after EV-depl FBS was larger than the S-EV pellet from no-HI FBS and HI-before EV-depl FBS. Transmission electron microscopy, protein quantification, and particle number evaluation showed that HI-after EV-depl significantly increased the protein amount of S-EVs but had no significant effect on L-EVs. Consequently, the protein quantity of S-EVs isolated from three cell lines cultured in media supplemented with HI-after EV-depl FBS was significantly increased. Quantitative mass spectrometry analysis of FBS-derived S-EVs showed that the EV protein content was different when FBS was HI after EV depletion compared to EVs isolated from no-HI FBS and HI-before EV-depl FBS. Moreover, we show that several quantified proteins could be ascribed to human origin, thus demonstrating that FBS bovine proteins can mistakenly be attributed to human cell-derived EVs. We conclude that HI of FBS performed after EV depletion results in changes in the proteome, with molecules that co-isolate with EVs and can contaminate EVs when used in subsequent cell cultures. Our recommendation is, therefore, to always perform HI of FBS prior to EV depletion.", "doi": "10.1002/jev2.12408", "pmid": "38263378", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service", "Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10805629"}], "notes": [], "created": "2024-11-15T12:11:19.768Z", "modified": "2024-11-27T16:35:05.846Z"}, {"entity": "publication", "iuid": "f8d136caf32f4442bf2e6c58cabda913", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f8d136caf32f4442bf2e6c58cabda913.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f8d136caf32f4442bf2e6c58cabda913"}}, "title": "Visualizing the Microbial N Uptake During Arctic Extreme Winter Warming Events Using Nanosims", "authors": [{"family": "Rasmussen", "given": "Laura Helene", "initials": "LH"}, {"family": "Danielsen", "given": "Birgitte Kortegaard", "initials": "BK"}, {"family": "Elberling", "given": "Bo", "initials": "B"}, {"family": "Kurzcy", "given": "Michael", "initials": "M"}, {"family": "Ranjbari", "given": "Elias", "initials": "E"}, {"family": "Micaroni", "given": "Massimo", "initials": "M"}, {"family": "Andresen", "given": "Louise C", "initials": "LC"}], "type": "posted-content", "published": "2024-00-00", "journal": {"title": "SSRN Journal", "issn": null, "issn-l": null, "volume": null, "issue": null, "pages": null}, "abstract": null, "doi": "10.2139/ssrn.4805454", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2024-11-15T12:10:21.209Z", "modified": "2025-12-18T21:25:12.785Z"}, {"entity": "publication", "iuid": "1d03aad5d13d48739bcae7e4e03873e1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1d03aad5d13d48739bcae7e4e03873e1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1d03aad5d13d48739bcae7e4e03873e1"}}, "title": "Strategies for Multimodal Image Data Transformation to a Common Format for Cloud Integration and Visualization", "authors": [{"family": "Camacho", "given": "Rafael", "initials": "R", "orcid": "0000-0003-2325-6407", "researcher": {"href": "https://publications.scilifelab.se/researcher/6a7a8cfe28634821984b078ce3246343.json"}}, {"family": "Berndtsson", "given": "Jens", "initials": "J", "orcid": "0000-0001-6627-8134", "researcher": {"href": "https://publications.scilifelab.se/researcher/7620a5c7c0f245a28771d57d7179abbd.json"}}, {"family": "Micaroni", "given": "Massimo", "initials": "M"}, {"family": "Zhang", "given": "Karl", "initials": "K", "orcid": "0009-0001-0790-1616", "researcher": {"href": "https://publications.scilifelab.se/researcher/c1880c8da747467795a011858ca2c9bf.json"}}, {"family": "Fernandez-Rodriguez", "given": "Julia", "initials": "J", "orcid": "0000-0003-4522-0966", "researcher": {"href": "https://publications.scilifelab.se/researcher/3bd9c743e99d479cb752aeec947acab3.json"}}], "type": "journal-article", "published": "2024-00-00", "journal": {"title": "BIO Web Conf.", "issn": "2117-4458", "volume": "129", "pages": "13019", "issn-l": null}, "abstract": null, "doi": "10.1051/bioconf/202412913019", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2024-11-15T12:01:54.662Z", "modified": "2025-12-04T19:30:59.547Z"}, {"entity": "publication", "iuid": "76e246453002491da312f21702a9294e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/76e246453002491da312f21702a9294e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/76e246453002491da312f21702a9294e"}}, "title": "A surface passivated fluorinated polymer nanocomposite for carbon monoxide resistant plasmonic hydrogen sensing", "authors": [{"family": "\u00d6stergren", "given": "I", "initials": "I", "orcid": "0000-0002-2431-0746", "researcher": {"href": "https://publications.scilifelab.se/researcher/969b5508235e4e14a7654c71cb426bb1.json"}}, {"family": "Darmadi", "given": "I", "initials": "I", "orcid": "0000-0002-5921-9336", "researcher": {"href": "https://publications.scilifelab.se/researcher/d24542fa29854812a58bc1906bdeaf8a.json"}}, {"family": "Lerch", "given": "S", "initials": "S"}, {"family": "da Silva", "given": "R R", "initials": "RR"}, {"family": "Craighero", "given": "M", "initials": "M"}, {"family": "Paleti", "given": "S H K", "initials": "SHK"}, {"family": "Moth-Poulsen", "given": "K", "initials": "K", "orcid": "0000-0003-4018-4927", "researcher": {"href": "https://publications.scilifelab.se/researcher/5807cc241ba24cf4a7841086d72dc3b9.json"}}, {"family": "Langhammer", "given": "C", "initials": "C", "orcid": "0000-0003-2180-1379", "researcher": {"href": "https://publications.scilifelab.se/researcher/17178716c3964e53933ddacffe70cc9a.json"}}, {"family": "M\u00fcller", "given": "C", "initials": "C", "orcid": "0000-0001-7859-7909", "researcher": {"href": "https://publications.scilifelab.se/researcher/7fc06198eb0c4a3eb17d052d8ef124ae.json"}}], "type": "journal-article", "published": "2024-00-00", "journal": {"title": "J. Mater. Chem. A", "issn": "2050-7488", "volume": "12", "issue": "13", "pages": "7906-7915", "issn-l": null}, "abstract": null, "doi": "10.1039/d4ta00055b", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2024-11-15T12:09:56.685Z", "modified": "2025-12-04T19:30:16.508Z"}, {"entity": "publication", "iuid": "302f2534ae134565a2017ff2f1526be5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/302f2534ae134565a2017ff2f1526be5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/302f2534ae134565a2017ff2f1526be5"}}, "title": "Three-dimensional reconstruction of interstitial extracellular vesicles in human liver as determined by electron tomography.", "authors": [{"family": "Olofsson Bagge", "given": "Roger", "initials": "R"}, {"family": "Berndtsson", "given": "Jens", "initials": "J", "orcid": "0000-0001-6627-8134", "researcher": {"href": "https://publications.scilifelab.se/researcher/7620a5c7c0f245a28771d57d7179abbd.json"}}, {"family": "Urz\u00ec", "given": "Ornella", "initials": "O"}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J"}, {"family": "Micaroni", "given": "Massimo", "initials": "M"}, {"family": "Crescitelli", "given": "Rossella", "initials": "R", "orcid": "0000-0002-1714-3169", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d4b955f26ca4a679deb090e30d0ccf1.json"}}], "type": "journal article", "published": "2023-12-00", "journal": {"title": "J Extracell Vesicles", "issn": "2001-3078", "volume": "12", "issue": "12", "pages": "e12380", "issn-l": "2001-3078"}, "abstract": "Extracellular vesicles (EVs) are lipid bilayer nanoparticles involved in cell-cell communication that are released into the extracellular space by all cell types. The cargo of EVs includes proteins, lipids, nucleic acids, and metabolites reflecting their cell of origin. EVs have recently been isolated directly from solid tissues, and this may provide insights into how EVs mediate communication between cells in vivo. Even though EVs have been isolated from tissues, their point of origin when they are in the interstitial space has been uncertain. In this study, we performed three-dimensional (3D) reconstruction using transmission electron tomography of metastatic and normal liver tissues with a focus on the presence of EVs in the interstitium. After chemical fixation of the samples and subsequent embedding of tissue pieces in resin, ultrathin slices (300 nm) were cut and imaged on a 120 ekV transmission electron microscopy as a tilt series (a series of subsequent images tilted at different angles). These were then computationally illustrated in a 3D manner to reconstruct the imaged tissue volume. We identified the cells delimiting the interstitial space in both types of tissues, and small distinct spherical structures with a diameter of 30-200 nm were identified between the cells. These round structures appeared to be more abundant in metastatic tissue compared to normal tissue. We suggest that the observed spherical structures in the interstitium of the metastatic and non-metastatic liver represent EVs. This work thus provides the first 3D visualization of EVs in human tissue.", "doi": "10.1002/jev2.12380", "pmid": "38010190", "labels": {"Integrated Microscopy Technologies Gothenburg": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10680575"}], "notes": [], "created": "2023-12-01T10:43:39.007Z", "modified": "2023-12-01T10:43:55.171Z"}, {"entity": "publication", "iuid": "e842d4e2fc484d519d7074d4e56d443c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e842d4e2fc484d519d7074d4e56d443c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e842d4e2fc484d519d7074d4e56d443c"}}, "title": "Defective Uterine Spiral Artery Remodeling and Placental Senescence in a Pregnant Rat Model of Polycystic Ovary Syndrome.", "authors": [{"family": "Hu", "given": "Min", "initials": "M"}, {"family": "Zhang", "given": "Yuehui", "initials": "Y"}, {"family": "Zhang", "given": "Xu", "initials": "X"}, {"family": "Zhang", "given": "XiuYing", "initials": "X"}, {"family": "Huang", "given": "Xinyue", "initials": "X"}, {"family": "Lu", "given": "Yaxing", "initials": "Y"}, {"family": "Li", "given": "Yijia", "initials": "Y"}, {"family": "Br\u00e4nnstr\u00f6m", "given": "Mats", "initials": "M"}, {"family": "Sferruzzi-Perri", "given": "Amanda N", "initials": "AN"}, {"family": "Shao", "given": "Linus R", "initials": "LR"}, {"family": "Billig", "given": "H\u00e5kan", "initials": "H"}], "type": "journal article", "published": "2023-12-00", "journal": {"title": "Am. J. Pathol.", "issn": "1525-2191", "volume": "193", "issue": "12", "pages": "1916-1935", "issn-l": "0002-9440"}, "abstract": "Pregnancy-related problems have been linked to impairments in maternal uterine spiral artery (SpA) remodeling. The mechanisms underlying this association are still unclear. It is also unclear whether hyperandrogenism and insulin resistance, the two common manifestations of polycystic ovary syndrome, affect uterine SpA remodeling. We verified previous work in which exposure to 5-dihydrotestosterone (DHT) and insulin (INS) in rats during pregnancy resulted in hyperandrogenism, insulin intolerance, and higher fetal mortality. Exposure to DHT and INS dysregulated the expression of angiogenesis-related genes in the uterus and placenta and also decreased expression of endothelial nitric oxide synthase and matrix metallopeptidases 2 and 9, increased fibrotic collagen deposits in the uterus, and reduced expression of marker genes for SpA-associated trophoblast giant cells. These changes were related to a greater proportion of unremodeled uterine SpAs and a smaller proportion of highly remodeled arteries in DHT + INS-exposed rats. Placentas from DHT + INS-exposed rats exhibited decreased basal and labyrinth zone regions, reduced maternal blood spaces, diminished labyrinth vascularity, and an imbalance in the abundance of vascular and smooth muscle proteins. Furthermore, placentas from DHT + INS-exposed rats showed expression of placental insufficiency markers and a significant increase in cell senescence-associated protein levels. Altogether, this work demonstrates that increased pregnancy complications in polycystic ovary syndrome may be mediated by problems with uterine SpA remodeling, placental functionality, and placental senescence.", "doi": "10.1016/j.ajpath.2023.08.008", "pmid": "37689383", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S0002-9440(23)00315-2"}], "notes": [], "created": "2023-12-01T10:46:37.723Z", "modified": "2023-12-01T10:46:37.727Z"}, {"entity": "publication", "iuid": "5dcce0e7161644cf861a09e161ee19bf", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5dcce0e7161644cf861a09e161ee19bf.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5dcce0e7161644cf861a09e161ee19bf"}}, "title": "Graphene Oxide Attenuates Toxicity of Amyloid\u2010\u03b2 Aggregates in Yeast by Promoting Disassembly and Boosting Cellular Stress Response", "authors": [{"family": "Chen", "given": "Xin", "initials": "X", "orcid": "0000-0003-2788-1314", "researcher": {"href": "https://publications.scilifelab.se/researcher/d1b77832f3ca408fa8dc1414d8f46552.json"}}, {"family": "Pandit", "given": "Santosh", "initials": "S", "orcid": "0000-0002-8357-758X", "researcher": {"href": "https://publications.scilifelab.se/researcher/ef2b4388693848c68cf42174ddeb65be.json"}}, {"family": "Shi", "given": "Lei", "initials": "L", "orcid": "0000-0002-2981-4150", "researcher": {"href": "https://publications.scilifelab.se/researcher/7389ba41b5f449f6b2f2dc7311235f92.json"}}, {"family": "Ravikumar", "given": "Vaishnavi", "initials": "V"}, {"family": "K\u00f8hler", "given": "Julie Bonne", "initials": "JB"}, {"family": "Svetlicic", "given": "Ema", "initials": "E", "orcid": "0009-0001-5062-5805", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f3d7fa745d34006ba08ceed4ff2c452.json"}}, {"family": "Cao", "given": "Zhejian", "initials": "Z", "orcid": "0000-0002-3216-6270", "researcher": {"href": "https://publications.scilifelab.se/researcher/ac0e5a4dc3e64d00826cdaf7ef25b390.json"}}, {"family": "Garg", "given": "Abhroop", "initials": "A"}, {"family": "Petranovic", "given": "Dina", "initials": "D"}, {"family": "Mijakovic", "given": "Ivan", "initials": "I", "orcid": "0000-0002-8860-6853", "researcher": {"href": "https://publications.scilifelab.se/researcher/c0e5dfcc215b494a860ca6d9254b0b56.json"}}], "type": "journal-article", "published": "2023-11-00", "journal": {"title": "Adv Funct Materials", "issn": "1616-301X", "volume": "33", "issue": "45", "issn-l": null}, "abstract": null, "doi": "10.1002/adfm.202304053", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2023-12-01T10:44:51.987Z", "modified": "2025-12-03T11:34:48.101Z"}, {"entity": "publication", "iuid": "5bce6333d0ca468d8cad3aa9924a36fd", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5bce6333d0ca468d8cad3aa9924a36fd.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5bce6333d0ca468d8cad3aa9924a36fd"}}, "title": "Reduction of body weight by increased loading is associated with activation of norepinephrine neurones in the medial nucleus of the solitary tract.", "authors": [{"family": "Zlatkovic", "given": "Jovana", "initials": "J"}, {"family": "Dalmau Gasull", "given": "Adri\u00e0", "initials": "A", "orcid": "0000-0002-8410-8048", "researcher": {"href": "https://publications.scilifelab.se/researcher/005cfa599fc346fcbcffdc4d2a28b17e.json"}}, {"family": "H\u00e4gg", "given": "Daniel", "initials": "D"}, {"family": "Font-Giron\u00e8s", "given": "Ferran", "initials": "F"}, {"family": "Bellman", "given": "Jakob", "initials": "J"}, {"family": "Meister", "given": "Bj\u00f6rn", "initials": "B"}, {"family": "Palsdottir", "given": "Vilborg", "initials": "V"}, {"family": "Ruud", "given": "Johan", "initials": "J"}, {"family": "Ohlsson", "given": "Claes", "initials": "C"}, {"family": "Dickson", "given": "Suzanne L", "initials": "SL"}, {"family": "Anesten", "given": "Fredrik", "initials": "F", "orcid": "0000-0001-8988-1163", "researcher": {"href": "https://publications.scilifelab.se/researcher/e2e7557ed439405cb5955bf1ac33852c.json"}}, {"family": "Jansson", "given": "John-Olov", "initials": "JO"}], "type": "journal article", "published": "2023-10-26", "journal": {"title": "J Neuroendocrinol", "issn": "1365-2826", "pages": "e13352", "issn-l": null}, "abstract": "We previously provided evidence supporting the existence of a novel leptin-independent body weight homeostat (\"the gravitostat\") that senses body weight and then initiates a homeostatic feed-back regulation of body weight. We, herein, hypothesize that this feed-back regulation involves a CNS mechanism. To identify populations of neurones of importance for the putative feed-back signal induced by increased loading, high-fat diet-fed rats or mice were implanted intraperitoneally or subcutaneously with capsules weighing \u223c15% (Load) or \u223c2.5% (Control) of body weight. At 3-5 days after implantation, neuronal activation was assessed in different parts of the brain/brainstem by immunohistochemical detection of FosB. Implantation of weighted capsules, both subcutaneous and intraperitoneal, induced FosB in specific neurones in the medial nucleus of the solitary tract (mNTS), known to integrate information about the metabolic status of the body. These neurones also expressed tyrosine hydroxylase (TH) and dopamine-beta-hydroxylase (DbH), a pattern typical of norepinephrine neurones. In functional studies, we specifically ablated norepinephrine neurones in mNTS, which attenuated the feed-back regulation of increased load on body weight and food intake. In conclusion, increased load appears to reduce body weight and food intake via activation of norepinephrine neurones in the mNTS.", "doi": "10.1111/jne.13352", "pmid": "37885347", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2023-12-01T10:52:44.484Z", "modified": "2023-12-01T10:52:44.581Z"}, {"entity": "publication", "iuid": "e02d48d0f6b647e8baf207b0270fd127", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e02d48d0f6b647e8baf207b0270fd127.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e02d48d0f6b647e8baf207b0270fd127"}}, "title": "Elevated Adipocyte Membrane Phospholipid Saturation Does Not Compromise Insulin Signaling.", "authors": [{"family": "Palmgren", "given": "Henrik", "initials": "H"}, {"family": "Petkevicius", "given": "Kasparas", "initials": "K"}, {"family": "Bartesaghi", "given": "Stefano", "initials": "S"}, {"family": "Ahnmark", "given": "Andrea", "initials": "A"}, {"family": "Ruiz", "given": "Mario", "initials": "M"}, {"family": "Nilsson", "given": "Ralf", "initials": "R"}, {"family": "L\u00f6fgren", "given": "Lars", "initials": "L"}, {"family": "Glover", "given": "Matthew S", "initials": "MS"}, {"family": "Andr\u00e9asson", "given": "Anne-Christine", "initials": "AC"}, {"family": "Andersson", "given": "Liselotte", "initials": "L"}, {"family": "Becquart", "given": "C\u00e9cile", "initials": "C"}, {"family": "Kurczy", "given": "Michael", "initials": "M"}, {"family": "Kull", "given": "Bengt", "initials": "B"}, {"family": "Wallin", "given": "Simonetta", "initials": "S"}, {"family": "Karlsson", "given": "Daniel", "initials": "D"}, {"family": "Hess", "given": "Sonja", "initials": "S"}, {"family": "Maresca", "given": "Marcello", "initials": "M"}, {"family": "Bohlooly-Y", "given": "Mohammad", "initials": "M"}, {"family": "Peng", "given": "Xiao-Rong", "initials": "XR"}, {"family": "Pilon", "given": "Marc", "initials": "M", "orcid": "0000-0003-3919-2882", "researcher": {"href": "https://publications.scilifelab.se/researcher/d45c4ecf9afe463c971af2de53a770a8.json"}}], "type": "journal article", "published": "2023-10-01", "journal": {"title": "Diabetes", "issn": "1939-327X", "volume": "72", "issue": "10", "pages": "1350-1363", "issn-l": "0012-1797"}, "abstract": "Increased saturated fatty acid (SFA) levels in membrane phospholipids have been implicated in the development of metabolic disease. Here, we tested the hypothesis that increased SFA content in cell membranes negatively impacts adipocyte insulin signaling. Preadipocyte cell models with elevated SFA levels in phospholipids were generated by disrupting the ADIPOR2 locus, which resulted in a striking twofold increase in SFA-containing phosphatidylcholines and phosphatidylethanolamines, which persisted in differentiated adipocytes. Similar changes in phospholipid composition were observed in white adipose tissues isolated from the ADIPOR2-knockout mice. The SFA levels in phospholipids could be further increased by treating ADIPOR2-deficient cells with palmitic acid and resulted in reduced membrane fluidity and endoplasmic reticulum stress in mouse and human preadipocytes. Strikingly, increased SFA levels in differentiated adipocyte phospholipids had no effect on adipocyte gene expression or insulin signaling in vitro. Similarly, increased adipocyte phospholipid saturation did not impair white adipose tissue function in vivo, even in mice fed a high-saturated fat diet at thermoneutrality. We conclude that increasing SFA levels in adipocyte phospholipids is well tolerated and does not affect adipocyte insulin signaling in vitro and in vivo.", "doi": "10.2337/db22-0293", "pmid": "36580483", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10545576"}, {"db": "pii", "key": "148231"}], "notes": [], "created": "2023-12-01T10:49:13.271Z", "modified": "2023-12-01T10:49:46.691Z"}, {"entity": "publication", "iuid": "1dd5848dc9c040d2a84511ee2e7ff50f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1dd5848dc9c040d2a84511ee2e7ff50f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1dd5848dc9c040d2a84511ee2e7ff50f"}}, "title": "Decontamination of biofilm-contaminated implant surfaces: An in vitro evaluation.", "authors": [{"family": "Ichioka", "given": "Yuki", "initials": "Y", "orcid": "0000-0003-0318-3167", "researcher": {"href": "https://publications.scilifelab.se/researcher/6de60717a790425a9304a30b8e2bc34e.json"}}, {"family": "Virto", "given": "Leire", "initials": "L", "orcid": "0000-0002-3376-5232", "researcher": {"href": "https://publications.scilifelab.se/researcher/d0dcfe4026e24752a6f5b2e3490c91dd.json"}}, {"family": "Nuevo", "given": "Paula", "initials": "P"}, {"family": "Gamonal", "given": "Juan Daniel", "initials": "JD"}, {"family": "Derks", "given": "Jan", "initials": "J", "orcid": "0000-0002-1133-6074", "researcher": {"href": "https://publications.scilifelab.se/researcher/459abeceb7c24480af9f0a444f3edd81.json"}}, {"family": "Larsson", "given": "Lena", "initials": "L"}, {"family": "Sanz", "given": "Mariano", "initials": "M", "orcid": "0000-0002-6293-5755", "researcher": {"href": "https://publications.scilifelab.se/researcher/2c2c7976938f4e32a7e6fc7f566115e7.json"}}, {"family": "Berglundh", "given": "Tord", "initials": "T", "orcid": "0000-0001-5864-6398", "researcher": {"href": "https://publications.scilifelab.se/researcher/2d29bd79b2914b47b00a0c1005b30b43.json"}}], "type": "journal article", "published": "2023-10-00", "journal": {"title": "Clin Oral Implants Res", "issn": "1600-0501", "volume": "34", "issue": "10", "pages": "1058-1072", "issn-l": null}, "abstract": "The aim of the present study was to evaluate the cleaning efficacy of two mechanical and two chemical protocols in the decontamination of implant surfaces.\n\nIn total, 123 commercially available implants were mounted in plastic models mimicking peri-implant circumferential intra-bony defects. A multispecies biofilm was grown on implant surfaces. Mechanical (air-polishing (AP), rotating titanium brush (TiB)) and chemical decontamination (alkaline electrolyzed water, N-acetyl-L-cysteine) protocols were used. Cleaning efficacy in terms of residual biofilm area, chemical surface properties, and bacterial counts were analyzed by scanning electron microscopy, energy-dispersive X-ray spectroscopy, and quantitative polymerase chain reaction.\n\nSurface decontamination protocols including use of an AP device or a rotating TiB were superior in terms of biofilm removal and in reducing atomic% of Carbon on implant surfaces when compared to methods restricted to wiping with gauze. The use of chemical agents as adjuncts to the mechanical cleaning protocols provided no relevant overall benefit over saline. No treatment modality, however, resulted in complete biofilm removal.\n\nAir-polishing and rotating TiB were more effective implant surface decontamination protocols than wiping with gauzes. Use of chemical agents did not improve cleaning efficacy.", "doi": "10.1111/clr.14136", "pmid": "37469250", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2023-12-01T10:46:02.277Z", "modified": "2023-12-01T10:46:02.370Z"}, {"entity": "publication", "iuid": "57e0117b46834ba4be1ceefa899cd14b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/57e0117b46834ba4be1ceefa899cd14b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/57e0117b46834ba4be1ceefa899cd14b"}}, "title": "APP-BACE1 Interaction and Intracellular Localization Regulate A\u03b2 Production in iPSC-Derived Cortical Neurons.", "authors": [{"family": "Roselli", "given": "Sandra", "initials": "S", "orcid": "0000-0003-2998-3760", "researcher": {"href": "https://publications.scilifelab.se/researcher/967692ca9b2e43078b0f732e08133f0c.json"}}, {"family": "Satir", "given": "Tugce Munise", "initials": "TM", "orcid": "0000-0001-9021-1650", "researcher": {"href": "https://publications.scilifelab.se/researcher/ae8aad9da4a241e5b8fbfe9a9bc57624.json"}}, {"family": "Camacho", "given": "Rafael", "initials": "R", "orcid": "0000-0003-2325-6407", "researcher": {"href": "https://publications.scilifelab.se/researcher/6a7a8cfe28634821984b078ce3246343.json"}}, {"family": "Fruhw\u00fcrth", "given": "Stefanie", "initials": "S", "orcid": "0000-0003-4035-7330", "researcher": {"href": "https://publications.scilifelab.se/researcher/ed598b441d80455db788599f7cb307e9.json"}}, {"family": "Bergstr\u00f6m", "given": "Petra", "initials": "P", "orcid": "0000-0003-1803-165X", "researcher": {"href": "https://publications.scilifelab.se/researcher/2c7a0d0f6ee448e281dab1d9abf4f80c.json"}}, {"family": "Zetterberg", "given": "Henrik", "initials": "H", "orcid": "0000-0003-3930-4354", "researcher": {"href": "https://publications.scilifelab.se/researcher/85efee74eb4a4b38b63cf2823d204529.json"}}, {"family": "Agholme", "given": "Lotta", "initials": "L", "orcid": "0000-0003-3816-7474", "researcher": {"href": "https://publications.scilifelab.se/researcher/a7034ae6b9644a6fabd3bfb6d719459b.json"}}], "type": "journal article", "published": "2023-10-00", "journal": {"title": "Cell Mol Neurobiol", "issn": "1573-6830", "volume": "43", "issue": "7", "pages": "3653-3668", "issn-l": null}, "abstract": "Alzheimer's disease (AD) is characterized pathologically by amyloid \u03b2 (A\u03b2)-containing plaques. Generation of A\u03b2 from amyloid precursor protein (APP) by two enzymes, \u03b2- and \u03b3-secretase, has therefore been in the AD research spotlight for decades. Despite this, how the physical interaction of APP with the secretases influences APP processing is not fully understood. Herein, we compared two genetically identical human iPSC-derived neuronal cell types: low A\u03b2-secreting neuroprogenitor cells (NPCs) and high A\u03b2-secreting mature neurons, as models of low versus high A\u03b2 production. We investigated levels of substrate, enzymes and products of APP amyloidogenic processing and correlated them with the proximity of APP to \u03b2- and \u03b3-secretase in endo-lysosomal organelles. In mature neurons, increased colocalization of full-length APP with the \u03b2-secretase BACE1 correlated with increased \u03b2-cleavage product sAPP\u03b2. Increased flAPP/BACE1 colocalization was mainly found in early endosomes. In the same way, increased colocalization of APP-derived C-terminal fragment (CTF) with presenilin-1 (PSEN1), the catalytic subunit of \u03b3-secretase, was seen in neurons as compared to NPCs. Furthermore, most of the interaction of APP with BACE1 in low A\u03b2-secreting NPCs seemed to derive from CTF, the remaining APP part after BACE1 cleavage, indicating a possible novel product-enzyme inhibition. In conclusion, our results suggest that interaction of APP and APP cleavage products with their secretases can regulate A\u03b2 production both positively and negatively. \u03b2- and \u03b3-Secretases are difficult targets for AD treatment due to their ubiquitous nature and wide range of substrates. Therefore, targeting APP-secretase interactions could be a novel treatment strategy for AD. Colocalization of APP species with BACE1 in a novel model of low- versus high-A\u03b2 secretion-Two genetically identical human iPSC-derived neuronal cell types: low A\u03b2-secreting neuroprogenitor cells (NPCs) and high A\u03b2 secreting mature neurons, were compared. Increased full-length APP (flAPP)/BACE1 colocalization in early endosomes was seen in neurons, while APP-CTF/BACE1 colocalization was much higher than flAPP/BACE1 colocalization in NPCs, although the cellular location was not determined.", "doi": "10.1007/s10571-023-01374-0", "pmid": "37355492", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10477112"}, {"db": "pii", "key": "10.1007/s10571-023-01374-0"}], "notes": [], "created": "2023-12-01T10:50:59.915Z", "modified": "2023-12-01T10:51:00.090Z"}, {"entity": "publication", "iuid": "51d04c2da7f7422da934e0ed134bdb4f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/51d04c2da7f7422da934e0ed134bdb4f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/51d04c2da7f7422da934e0ed134bdb4f"}}, "title": "Inflammatory Gene Profile and Particle Presence in Peri-Implant Mucosa: a Pilot Study on 9 Patients.", "authors": [{"family": "Olander", "given": "Julia", "initials": "J"}, {"family": "Barkarmo", "given": "Sargon", "initials": "S"}, {"family": "Hammarstr\u00f6m Johansson", "given": "Petra", "initials": "P"}, {"family": "Wennerberg", "given": "Ann", "initials": "A"}, {"family": "Stenport", "given": "Victoria Franke", "initials": "VF"}], "type": "journal article", "published": "2023-09-30", "journal": {"title": "J Oral Maxillofac Res", "issn": "2029-283X", "volume": "14", "issue": "3", "pages": "e2", "issn-l": null}, "abstract": "The purpose of this pilot study is to compare gene expression in mucosa around dental implants with zirconia abutment to titanium and investigate presence of particles in mucosa samples and on implant heads.\n\nTen patients with a single implant supported prosthesis connected to zirconia or titanium abutments were invited at the five-year control. A clinical examination and a survey on experience of function and appearance were conducted. A mucosa biopsy taken in close vicinity to the implant were analysed by real-time polymerase chain reaction (qPCR) and presence of particles in a scanning electron microscope/energy-dispersive X-ray spectroscope (SEM/EDX). Cytological smear samples were collected and analysed through inductively coupled plasma mass spectrometry (ICP-MS) to investigate presence of particles on implant heads.\n\nIn total, 9 patients participated in the study, five with titanium abutments and four with zirconia abutments. All patients were satisfied with function and aesthetics. Titanium and iron particles were detected in mucosa biopsies. The ICP - MS analysis demonstrated presence of zirconia and titanium. Several proinflammatory genes were upregulated in the zirconia abutment group.\n\nAround zirconia abutments a slight increase in proinflammatory response and amount of wear particles was seen as compared to titanium. Wear particles of titanium were present in all soft tissue samples, however zirconia particles only in the samples from implants heads/mucosa with zirconia abutments.", "doi": "10.5037/jomr.2023.14302", "pmid": "37969950", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10645473"}, {"db": "pii", "key": "v14n3e2ht"}], "notes": [], "created": "2023-12-01T10:48:40.488Z", "modified": "2023-12-01T10:48:40.518Z"}, {"entity": "publication", "iuid": "68e5e56f6e754304be4e58797b91095a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/68e5e56f6e754304be4e58797b91095a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/68e5e56f6e754304be4e58797b91095a"}}, "title": "The yeast guanine nucleotide exchange factor Sec7 is a bottleneck in spatial protein quality control and detoxifies neurological disease proteins.", "authors": [{"family": "Babazadeh", "given": "Roja", "initials": "R"}, {"family": "Schneider", "given": "Kara L", "initials": "KL"}, {"family": "Fischbach", "given": "Arthur", "initials": "A"}, {"family": "Hao", "given": "Xinxin", "initials": "X"}, {"family": "Liu", "given": "Beidong", "initials": "B"}, {"family": "Nystrom", "given": "Thomas", "initials": "T"}], "type": "journal article", "published": "2023-08-28", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "13", "issue": "1", "pages": "14068", "issn-l": "2045-2322"}, "abstract": "ER-to-Golgi trafficking partakes in the sorting of misfolded cytoplasmic proteins to reduce their cytological toxicity. We show here that yeast Sec7, a protein involved in proliferation of the Golgi, is part of this pathway and participates in an Hsp70-dependent formation of insoluble protein deposits (IPOD). Sec7 associates with the disaggregase Hsp104 during a mild heat shock and increases the rate of Hsp104 diffusion in an Hsp70-dependent manner when overproduced. Sec7 overproduction increased formation of IPODs from smaller aggregates and mitigated the toxicity of Huntingtin exon-1 upon heat stress while Sec7 depletion increased sensitivity to a\u1e9e42 of the Alzheimer's disease and \u03b1-synuclein of the Parkinson's disease, suggesting a role of Sec7 in mitigating proteotoxicity.", "doi": "10.1038/s41598-023-41188-0", "pmid": "37640758", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10462735"}, {"db": "pii", "key": "10.1038/s41598-023-41188-0"}], "notes": [], "created": "2023-12-01T10:42:12.669Z", "modified": "2023-12-01T10:42:12.673Z"}, {"entity": "publication", "iuid": "963edc019dcf47f2bc6f2fedac1024fd", "links": {"self": {"href": "https://publications.scilifelab.se/publication/963edc019dcf47f2bc6f2fedac1024fd.json"}, "display": {"href": "https://publications.scilifelab.se/publication/963edc019dcf47f2bc6f2fedac1024fd"}}, "title": "Multiphoton characterization and live cell imaging using fluorescent adenine analogue 2CNqA.", "authors": [{"family": "Nilsson", "given": "Jesper R", "initials": "JR"}, {"family": "Benitez-Martin", "given": "Carlos", "initials": "C", "orcid": "0000-0003-1821-9388", "researcher": {"href": "https://publications.scilifelab.se/researcher/d1fcdd6e053b462998fe7f463be60d96.json"}}, {"family": "Sansom", "given": "Henry G", "initials": "HG"}, {"family": "Pfeiffer", "given": "Pauline", "initials": "P"}, {"family": "Baladi", "given": "Tom", "initials": "T", "orcid": "0000-0003-3421-9417", "researcher": {"href": "https://publications.scilifelab.se/researcher/98ee438479aa4edeb47098227333f19f.json"}}, {"family": "Le", "given": "Hoang-Ngoan", "initials": "HN"}, {"family": "Dahl\u00e9n", "given": "Anders", "initials": "A"}, {"family": "Magennis", "given": "Steven W", "initials": "SW", "orcid": "0000-0002-4327-8366", "researcher": {"href": "https://publications.scilifelab.se/researcher/78ea6bb7f2a3437e83e782d83524726e.json"}}, {"family": "Wilhelmsson", "given": "L Marcus", "initials": "LM", "orcid": "0000-0002-2193-6639", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ff080464d7b468db29fc714915cfa6c.json"}}], "type": "journal article", "published": "2023-08-02", "journal": {"title": "Phys Chem Chem Phys", "issn": "1463-9084", "volume": "25", "issue": "30", "pages": "20218-20224", "issn-l": "1463-9076"}, "abstract": "Fluorescent nucleobase analogues (FBAs) are established tools for studying oligonucleotide structure, dynamics and interactions, and have recently also emerged as an attractive option for labeling RNA-based therapeutics. A recognized drawback of FBAs, however, is that they typically require excitation in the UV region, which for imaging in biological samples may have disadvantages related to phototoxicity, tissue penetration, and out-of-focus photobleaching. Multiphoton excitation has the potential to alleviate these issues and therefore, in this work, we characterize the multiphoton absorption properties and detectability of the highly fluorescent quadracyclic adenine analogue 2CNqA as a ribonucleotide monomer as well as incorporated, at one or two positions, into a 16mer antisense oligonucleotide (ASO). We found that 2CNqA has a two-photon absorption cross section that, among FBAs, is exceptionally high, with values of \u03c32PA(700 nm) = 5.8 GM, 6.8 GM, and 13 GM for the monomer, single-, and double-labelled oligonucleotide, respectively. Using fluorescence correlation spectroscopy, we show that the 2CNqA has a high 2P brightness as the monomer and when incorporated into the ASO, comparing favorably to other FBAs. We furthermore demonstrate the usefulness of the 2P imaging mode for improving detectability of 2CNqA-labelled ASOs in live cells.", "doi": "10.1039/d3cp01147j", "pmid": "37475592", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2023-12-01T10:48:25.609Z", "modified": "2023-12-01T10:48:25.711Z"}, {"entity": "publication", "iuid": "ac80952db59f49f3b1c15eec06392e65", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ac80952db59f49f3b1c15eec06392e65.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ac80952db59f49f3b1c15eec06392e65"}}, "title": "Two different isoforms of osteopontin modulate myelination and axonal integrity.", "authors": [{"family": "Nilsson", "given": "Gisela", "initials": "G", "orcid": "0000-0003-4423-5082", "researcher": {"href": "https://publications.scilifelab.se/researcher/c07681f5131b4c58bd71119c56f5d435.json"}}, {"family": "Mottahedin", "given": "Amin", "initials": "A", "orcid": "0000-0002-3677-2198", "researcher": {"href": "https://publications.scilifelab.se/researcher/82a4c6f53ae241edaf5147addb082567.json"}}, {"family": "Zelco", "given": "Aura", "initials": "A", "orcid": "0000-0002-5851-6355", "researcher": {"href": "https://publications.scilifelab.se/researcher/f66e84b556ab4454b96ba929cfa2b104.json"}}, {"family": "Lauschke", "given": "Volker M", "initials": "VM", "orcid": "0000-0002-1140-6204", "researcher": {"href": "https://publications.scilifelab.se/researcher/29c123916fbf4948a911560c1a259496.json"}}, {"family": "Ek", "given": "C Joakim", "initials": "CJ", "orcid": "0000-0002-5764-7679", "researcher": {"href": "https://publications.scilifelab.se/researcher/991c705e88dd472cae9e98ad540660ab.json"}}, {"family": "Song", "given": "Juan", "initials": "J"}, {"family": "Ardalan", "given": "Maryam", "initials": "M", "orcid": "0000-0003-3414-1584", "researcher": {"href": "https://publications.scilifelab.se/researcher/ceef7775ba414a1ab0f5039db2f0014b.json"}}, {"family": "Hua", "given": "Sha", "initials": "S"}, {"family": "Zhang", "given": "Xiaoli", "initials": "X", "orcid": "0000-0001-5111-9405", "researcher": {"href": "https://publications.scilifelab.se/researcher/3d5f1af1b5f3452d8db56bbe3eea440c.json"}}, {"family": "Mallard", "given": "Carina", "initials": "C", "orcid": "0000-0001-8953-919X", "researcher": {"href": "https://publications.scilifelab.se/researcher/2d0fa7de10554b5bb5a0e1ee64902aa1.json"}}, {"family": "Hagberg", "given": "Henrik", "initials": "H", "orcid": "0000-0003-3962-1448", "researcher": {"href": "https://publications.scilifelab.se/researcher/ca1150b5f07c441096f2716c0564e1d0.json"}}, {"family": "Leavenworth", "given": "Jianmei W", "initials": "JW", "orcid": "0000-0002-4100-9883", "researcher": {"href": "https://publications.scilifelab.se/researcher/d1b287368adf4edabe671e33ab56c550.json"}}, {"family": "Wang", "given": "Xiaoyang", "initials": "X", "orcid": "0000-0001-9717-8160", "researcher": {"href": "https://publications.scilifelab.se/researcher/70fbed19bca84bec93f558168444227a.json"}}], "type": "journal article", "published": "2023-08-00", "journal": {"title": "FASEB Bioadv", "issn": "2573-9832", "issn-l": null, "volume": "5", "issue": "8", "pages": "336-353"}, "abstract": "Abnormal myelination underlies the pathology of white matter diseases such as preterm white matter injury and multiple sclerosis. Osteopontin (OPN) has been suggested to play a role in myelination. Murine OPN mRNA is translated into a secreted isoform (sOPN) or an intracellular isoform (iOPN). Whether there is an isoform-specific involvement of OPN in myelination is unknown. Here we generated mouse models that either lacked both OPN isoforms in all cells (OPN-KO) or lacked sOPN systemically but expressed iOPN specifically in oligodendrocytes (OLs-iOPN-KI). Transcriptome analysis of isolated oligodendrocytes from the neonatal brain showed that genes and pathways related to increase of myelination and altered cell cycle control were enriched in the absence of the two OPN isoforms in OPN-KO mice compared to control mice. Accordingly, adult OPN-KO mice showed an increased axonal myelination, as revealed by transmission electron microscopy imaging, and increased expression of myelin-related proteins. In contrast, neonatal oligodendrocytes from OLs-iOPN-KI mice compared to control mice showed differential regulation of genes and pathways related to the increase of cell adhesion, motility, and vasculature development, and the decrease of axonal/neuronal development. OLs-iOPN-KI mice showed abnormal myelin formation in the early phase of myelination in young mice and signs of axonal degeneration in adulthood. These results suggest an OPN isoform-specific involvement, and a possible interplay between the isoforms, in myelination, and axonal integrity. Thus, the two isoforms of OPN need to be separately considered in therapeutic strategies targeting OPN in white matter injury and diseases.", "doi": "10.1096/fba.2023-00030", "pmid": "37554545", "labels": {"Clinical Genomics Gothenburg": "Service", "Integrated Microscopy Technologies Gothenburg": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10405251"}, {"db": "pii", "key": "FBA21405"}], "notes": [], "created": "2023-11-30T22:35:19.238Z", "modified": "2023-12-03T13:28:50.770Z"}, {"entity": "publication", "iuid": "865546bfe4f74204bd6971bf9b7f056b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/865546bfe4f74204bd6971bf9b7f056b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/865546bfe4f74204bd6971bf9b7f056b"}}, "title": "Surface decontamination of explanted peri-implantitis-affected implants.", "authors": [{"family": "Ichioka", "given": "Yuki", "initials": "Y", "orcid": "0000-0003-0318-3167", "researcher": {"href": "https://publications.scilifelab.se/researcher/6de60717a790425a9304a30b8e2bc34e.json"}}, {"family": "Derks", "given": "Jan", "initials": "J", "orcid": "0000-0002-1133-6074", "researcher": {"href": "https://publications.scilifelab.se/researcher/459abeceb7c24480af9f0a444f3edd81.json"}}, {"family": "Larsson", "given": "Lena", "initials": "L"}, {"family": "Berglundh", "given": "Tord", "initials": "T", "orcid": "0000-0001-5864-6398", "researcher": {"href": "https://publications.scilifelab.se/researcher/2d29bd79b2914b47b00a0c1005b30b43.json"}}], "type": "journal article", "published": "2023-08-00", "journal": {"title": "J Clin Periodontol", "issn": "1600-051X", "volume": "50", "issue": "8", "pages": "1113-1122", "issn-l": null}, "abstract": "The present study aimed at evaluating the effect of air-polishing (AP) and a combination of AP and alkaline electrolysed water (AEW) in surface decontamination of explanted peri-implantitis-affected implants.\n\nTwenty-five patients with 34 dental implants scheduled for explantation due to severe peri-implantitis were included. Following implant removal, the apical part of each implant was embedded in acrylic blocks. Implants were randomly allocated to surface decontamination using AP with or without AEW. Four implants were left untreated and used as negative controls. Specimens were analysed using scanning electron microscopy (SEM) and energy-dispersive x-ray spectroscopy (EDS). Area of residual bacteria was the primary outcome.\n\nSEM analysis revealed that both treatment protocols were effective in biofilm removal and only small proportions of target areas of the implants showed residual bacterial or mineralized deposits. Although differences between the treatment protocols were small, implant thread loci (top/flank/valley), zones of the implant (apical/middle/coronal), implant surface characteristics and gender influenced the results. In addition, EDS analysis showed that zones influenced the atomic% of carbon and calcium and that implant surface characteristics affected the atomic% of titanium.\n\nAP, with or without AEW, is an effective method in removing biofilm from peri-implantitis-affected implants.", "doi": "10.1111/jcpe.13836", "pmid": "37271864", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2023-12-01T10:45:46.555Z", "modified": "2023-12-01T10:45:46.590Z"}, {"entity": "publication", "iuid": "e1a6a9d248b049118831fcf9d7b3d7db", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e1a6a9d248b049118831fcf9d7b3d7db.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e1a6a9d248b049118831fcf9d7b3d7db"}}, "title": "Quantitative Nanoscale Secondary Ion Mass Spectrometry (NanoSIMS) Imaging of Individual Vesicles to Investigate the Relation between Fraction of Chemical Release and Vesicle Size.", "authors": [{"family": "Nguyen", "given": "Tho Duc Khanh", "initials": "TDK"}, {"family": "Rabasco", "given": "Stefania", "initials": "S"}, {"family": "Lork", "given": "Alicia A", "initials": "AA"}, {"family": "Toit", "given": "Andre Du", "initials": "AD"}, {"family": "Ewing", "given": "Andrew G", "initials": "AG", "orcid": "0000-0002-2084-0133", "researcher": {"href": "https://publications.scilifelab.se/researcher/c6ecb82dc7a6423fa0876822f5568e1b.json"}}], "type": "journal article", "published": "2023-07-10", "journal": {"title": "Angew. Chem. Int. Ed. Engl.", "issn": "1521-3773", "volume": "62", "issue": "28", "pages": "e202304098", "issn-l": "1433-7851"}, "abstract": "We used correlative transmission electron microscopy (TEM) and nanoscale secondary ion mass spectrometry (NanoSIMS) imaging to quantify the contents of subvesicular compartments, and to measure the partial release fraction of 13 C-dopamine in cellular nanovesicles as a function of size. Three modes of exocytosis comprise full release, kiss-and-run, and partial release. The latter has been subject to scientific debate, despite a growing amount of supporting literature. We tailored culturing procedures to alter vesicle size and definitively show no size correlation with the fraction of partial release. In NanoSIMS images, vesicle content was indicated by the presence of isotopic dopamine, while vesicles which underwent partial release were identified by the presence of an 127 I-labelled drug, to which they were exposed during exocytosis allowing entry into the open vesicle prior to its closing again. Demonstration of similar partial release fractions indicates that this mode of exocytosis is predominant across a wide range of vesicle sizes.", "doi": "10.1002/anie.202304098", "pmid": "37195146", "labels": {"Integrated Microscopy Technologies Gothenburg": "Technology development"}, "xrefs": [], "notes": [], "created": "2023-12-01T10:47:47.303Z", "modified": "2023-12-01T10:47:47.311Z"}, {"entity": "publication", "iuid": "faf07ebd88b44cbb8159cf13d69f1108", "links": {"self": {"href": "https://publications.scilifelab.se/publication/faf07ebd88b44cbb8159cf13d69f1108.json"}, "display": {"href": "https://publications.scilifelab.se/publication/faf07ebd88b44cbb8159cf13d69f1108"}}, "title": "Cardiomyocyte-specific PCSK9 deficiency compromises mitochondrial bioenergetics and heart function.", "authors": [{"family": "Laudette", "given": "Marion", "initials": "M"}, {"family": "Lindbom", "given": "Malin", "initials": "M"}, {"family": "Arif", "given": "Muhammad", "initials": "M", "orcid": "0000-0003-2261-0881", "researcher": {"href": "https://publications.scilifelab.se/researcher/fbe369c4e07c44c09dcf64a3c18d833e.json"}}, {"family": "Cinato", "given": "Mathieu", "initials": "M", "orcid": "0000-0002-8490-4335", "researcher": {"href": "https://publications.scilifelab.se/researcher/caecf7dcbc1b47639e00f683617632a2.json"}}, {"family": "Ruiz", "given": "Mario", "initials": "M"}, {"family": "Doran", "given": "Stephen", "initials": "S", "orcid": "0000-0002-9236-5407", "researcher": {"href": "https://publications.scilifelab.se/researcher/52635955f5e24f9c9a6bae8b0ebc0926.json"}}, {"family": "Miljanovic", "given": "Azra", "initials": "A"}, {"family": "Rutberg", "given": "Mikael", "initials": "M"}, {"family": "Andersson", "given": "Linda", "initials": "L"}, {"family": "Klevstig", "given": "Martina", "initials": "M"}, {"family": "Henricsson", "given": "Marcus", "initials": "M", "orcid": "0000-0002-4202-0339", "researcher": {"href": "https://publications.scilifelab.se/researcher/01a323cbf0a24269bd32bfc34539e021.json"}}, {"family": "Bergh", "given": "Per-Olof", "initials": "PO"}, {"family": "Bollano", "given": "Entela", "initials": "E"}, {"family": "Aung", "given": "Nay", "initials": "N", "orcid": "0000-0001-5095-1611", "researcher": {"href": "https://publications.scilifelab.se/researcher/246af6f2f0704302a2919c23d4b831c0.json"}}, {"family": "Gustav Smith", "given": "J", "initials": "J"}, {"family": "Pilon", "given": "Marc", "initials": "M"}, {"family": "Hy\u00f6tyl\u00e4inen", "given": "Tuulia", "initials": "T", "orcid": "0000-0002-1389-8302", "researcher": {"href": "https://publications.scilifelab.se/researcher/33d97cc166ee466aa69ab8c825c28b45.json"}}, {"family": "Ore\u0161i\u010d", "given": "Matej", "initials": "M"}, {"family": "Perkins", "given": "Rosie", "initials": "R"}, {"family": "Mardinoglu", "given": "Adil", "initials": "A"}, {"family": "Levin", "given": "Malin C", "initials": "MC"}, {"family": "Bor\u00e9n", "given": "Jan", "initials": "J", "orcid": "0000-0003-0786-8091", "researcher": {"href": "https://publications.scilifelab.se/researcher/1e85f6d287ce4c60a7b35b287efb4f79.json"}}], "type": "journal article", "published": "2023-07-04", "journal": {"title": "Cardiovasc. Res.", "issn": "1755-3245", "volume": "119", "issue": "7", "pages": "1537-1552", "issn-l": "0008-6363"}, "abstract": "Pro-protein convertase subtilisin-kexin type 9 (PCSK9), which is expressed mainly in the liver and at low levels in the heart, regulates cholesterol levels by directing low-density lipoprotein receptors to degradation. Studies to determine the role of PCSK9 in the heart are complicated by the close link between cardiac function and systemic lipid metabolism. Here, we sought to elucidate the function of PCSK9 specifically in the heart by generating and analysing mice with cardiomyocyte-specific Pcsk9 deficiency (CM-Pcsk9-/- mice) and by silencing Pcsk9 acutely in a cell culture model of adult cardiomyocyte-like cells.\n\nMice with cardiomyocyte-specific deletion of Pcsk9 had reduced contractile capacity, impaired cardiac function, and left ventricular dilatation at 28 weeks of age and died prematurely. Transcriptomic analyses revealed alterations of signalling pathways linked to cardiomyopathy and energy metabolism in hearts from CM-Pcsk9-/- mice vs. wild-type littermates. In agreement, levels of genes and proteins involved in mitochondrial metabolism were reduced in CM-Pcsk9-/- hearts. By using a Seahorse flux analyser, we showed that mitochondrial but not glycolytic function was impaired in cardiomyocytes from CM-Pcsk9-/- mice. We further showed that assembly and activity of electron transport chain (ETC) complexes were altered in isolated mitochondria from CM-Pcsk9-/- mice. Circulating lipid levels were unchanged in CM-Pcsk9-/- mice, but the lipid composition of mitochondrial membranes was altered. In addition, cardiomyocytes from CM-Pcsk9-/- mice had an increased number of mitochondria-endoplasmic reticulum contacts and alterations in the morphology of cristae, the physical location of the ETC complexes. We also showed that acute Pcsk9 silencing in adult cardiomyocyte-like cells reduced the activity of ETC complexes and impaired mitochondrial metabolism.\n\nPCSK9, despite its low expression in cardiomyocytes, contributes to cardiac metabolic function, and PCSK9 deficiency in cardiomyocytes is linked to cardiomyopathy, impaired heart function, and compromised energy production.", "doi": "10.1093/cvr/cvad041", "pmid": "36880401", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10318396"}, {"db": "pii", "key": "7070420"}], "notes": [], "created": "2023-12-01T10:47:21.390Z", "modified": "2023-12-01T10:47:21.524Z"}, {"entity": "publication", "iuid": "7ea962d923e7411b84994b78d79378f9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7ea962d923e7411b84994b78d79378f9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7ea962d923e7411b84994b78d79378f9"}}, "title": "Correlative Chemical Imaging Identifies Amyloid Peptide Signatures of Neuritic Plaques and Dystrophy in Human Sporadic Alzheimer's Disease.", "authors": [{"family": "Koutarapu", "given": "Srinivas", "initials": "S"}, {"family": "Ge", "given": "Junyue", "initials": "J"}, {"family": "Jha", "given": "Durga", "initials": "D"}, {"family": "Blennow", "given": "Kaj", "initials": "K"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H", "orcid": "0000-0003-3930-4354", "researcher": {"href": "https://publications.scilifelab.se/researcher/85efee74eb4a4b38b63cf2823d204529.json"}}, {"family": "Lashley", "given": "Tammaryn", "initials": "T"}, {"family": "Michno", "given": "Wojciech", "initials": "W", "orcid": "0000-0002-3096-3604", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b4307eb6e45426e8176337e88c9c344.json"}}, {"family": "Hanrieder", "given": "J\u00f6rg", "initials": "J", "orcid": "0000-0001-6059-198X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e65454100674f98bf8f2575093f2441.json"}}], "type": "journal article", "published": "2023-06-00", "journal": {"title": "Brain Connect", "issn": "2158-0022", "volume": "13", "issue": "5", "pages": "297-306", "issn-l": null}, "abstract": "Alzheimer's disease (AD) is the most common neurodegenerative disease. The predominantly sporadic form of AD is age-related, but the underlying pathogenic mechanisms remain not fully understood. Current efforts to combat the disease focus on the main pathological hallmarks, in particular beta-amyloid (A\u03b2) plaque pathology. According to the amyloid cascade hypothesis, A\u03b2 is the critical early initiator of AD pathogenesis. Plaque pathology is very heterogeneous, where a subset of plaques, neuritic plaques (NPs), are considered most neurotoxic rendering their in-depth characterization essential to understand A\u03b2 pathogenicity. Objective: To delineate the chemical traits specific to NP types, we investigated senile A\u03b2 pathology in the postmortem, human sporadic AD brain using advanced correlative biochemical imaging based on immunofluorescence (IF) microscopy and mass spectrometry imaging (MSI). Methods: Immunostaining-guided MSI identified distinct A\u03b2 signatures of NPs characterized by increased A\u03b21-42(ox) and A\u03b22-42. Moreover, correlation with a marker of dystrophy (reticulon 3 [RTN3]) identified key A\u03b2 species that both delineate NPs and display association with neuritic dystrophy. Results: Together, these correlative imaging data shed light on the complex biochemical architecture of NPs and associated dystrophic neurites. These in turn are obvious targets for disease-modifying treatment strategies, as well as novel biomarkers of A\u03b2 pathogenicity.Conclusion:", "doi": "10.1089/brain.2022.0047", "pmid": "36074939", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10398722"}], "notes": [], "created": "2023-02-16T08:26:30.200Z", "modified": "2023-12-01T10:46:54.067Z"}, {"entity": "publication", "iuid": "c7fa7c0f7e1641518831f53600f04e3a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c7fa7c0f7e1641518831f53600f04e3a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c7fa7c0f7e1641518831f53600f04e3a"}}, "title": "AdipoR2 recruits protein interactors to promote fatty acid elongation and membrane fluidity.", "authors": [{"family": "Ruiz", "given": "Mario", "initials": "M"}, {"family": "Devkota", "given": "Ranjan", "initials": "R"}, {"family": "Kaper", "given": "Delaney", "initials": "D"}, {"family": "Ruhanen", "given": "Hanna", "initials": "H"}, {"family": "Busayavalasa", "given": "Kiran", "initials": "K"}, {"family": "Radovi\u0107", "given": "Uro\u0161", "initials": "U"}, {"family": "Henricsson", "given": "Marcus", "initials": "M"}, {"family": "K\u00e4kel\u00e4", "given": "Reijo", "initials": "R"}, {"family": "Bor\u00e9n", "given": "Jan", "initials": "J"}, {"family": "Pilon", "given": "Marc", "initials": "M"}], "type": "journal article", "published": "2023-06-00", "journal": {"title": "J. Biol. Chem.", "issn": "1083-351X", "volume": "299", "issue": "6", "pages": "104799", "issn-l": "0021-9258"}, "abstract": "The human AdipoR2 and its Caenorhabditis elegans homolog PAQR-2 are multipass plasma membrane proteins that protect cells against membrane rigidification. However, how AdipoR2 promotes membrane fluidity mechanistically is not clear. Using 13C-labeled fatty acids, we show that AdipoR2 can promote the elongation and incorporation of membrane-fluidizing polyunsaturated fatty acids into phospholipids. To elucidate the molecular basis of these activities, we performed immunoprecipitations of tagged AdipoR2 and PAQR-2 expressed in HEK293 cells or whole C. elegans, respectively, and identified coimmunoprecipitated proteins using mass spectrometry. We found that several of the evolutionarily conserved AdipoR2/PAQR-2 interactors are important for fatty acid elongation and incorporation into phospholipids. We experimentally verified some of these interactions, namely, with the dehydratase HACD3 that is essential for the third of four steps in long-chain fatty acid elongation and ACSL4 that is important for activation of unsaturated fatty acids and their channeling into phospholipids. We conclude that AdipoR2 and PAQR-2 can recruit protein interactors to promote the production and incorporation of unsaturated fatty acids into phospholipids.", "doi": "10.1016/j.jbc.2023.104799", "pmid": "37164154", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service", "Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10279913"}, {"db": "pii", "key": "S0021-9258(23)01827-6"}], "notes": [], "created": "2023-12-01T10:51:26.058Z", "modified": "2024-01-16T13:46:27.405Z"}, {"entity": "publication", "iuid": "8e4409137b2d4a079106e80bc6f25610", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8e4409137b2d4a079106e80bc6f25610.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8e4409137b2d4a079106e80bc6f25610"}}, "title": "Cisplatin toxicity is counteracted by the activation of the p38/ATF-7 signaling pathway in post-mitotic C. elegans.", "authors": [{"family": "Raj", "given": "Dorota", "initials": "D", "orcid": "0000-0002-7357-2902", "researcher": {"href": "https://publications.scilifelab.se/researcher/23ff7c388c2b43e3a9d3a3514fe5e049.json"}}, {"family": "Kraish", "given": "Bashar", "initials": "B"}, {"family": "Martikainen", "given": "Jari", "initials": "J", "orcid": "0000-0003-0366-1683", "researcher": {"href": "https://publications.scilifelab.se/researcher/dfd56b6dfb74494890131a51097996d8.json"}}, {"family": "Podraza-Farhanieh", "given": "Agnieszka", "initials": "A", "orcid": "0000-0002-1120-8216", "researcher": {"href": "https://publications.scilifelab.se/researcher/8244c5dad7974bc0a2a4ec38cc3e58ce.json"}}, {"family": "Kao", "given": "Gautam", "initials": "G", "orcid": "0000-0003-1313-3024", "researcher": {"href": "https://publications.scilifelab.se/researcher/4575b678a90740428136c9f5e1bdd53b.json"}}, {"family": "Naredi", "given": "Peter", "initials": "P", "orcid": "0000-0002-5652-0422", "researcher": {"href": "https://publications.scilifelab.se/researcher/a41ccd84008a4a94a29410451bc012c9.json"}}], "type": "journal article", "published": "2023-05-20", "journal": {"title": "Nat Commun", "issn": "2041-1723", "issn-l": "2041-1723", "volume": "14", "issue": "1", "pages": "2886"}, "abstract": "Cisplatin kills proliferating cells via DNA damage but also has profound effects on post-mitotic cells in tumors, kidneys, and neurons. However, the effects of cisplatin on post-mitotic cells are still poorly understood. Among model systems, C. elegans adults are unique in having completely post-mitotic somatic tissues. The p38 MAPK pathway controls ROS detoxification via SKN-1/NRF and immune responses via ATF-7/ATF2. Here, we show that p38 MAPK pathway mutants are sensitive to cisplatin, but while cisplatin exposure increases ROS levels, skn-1 mutants are resistant. Cisplatin exposure leads to phosphorylation of PMK-1/MAPK and ATF-7 and the IRE-1/TRF-1 signaling module functions upstream of the p38 MAPK pathway to activate signaling. We identify the response proteins whose increased abundance depends on IRE-1/p38 MAPK activity as well as cisplatin exposure. Four of these proteins are necessary for protection from cisplatin toxicity, which is characterized by necrotic death. We conclude that the p38 MAPK pathway-driven proteins are crucial for adult cisplatin resilience.", "doi": "10.1038/s41467-023-38568-5", "pmid": "37210583", "labels": {"Clinical Genomics Gothenburg": "Collaborative", "Integrated Microscopy Technologies Gothenburg": "Service", "Glycoproteomics and MS Proteomics": "Service", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC10199892"}, {"db": "pii", "key": "10.1038/s41467-023-38568-5"}], "notes": [], "created": "2023-11-30T22:37:44.515Z", "modified": "2024-01-16T13:46:27.417Z"}, {"entity": "publication", "iuid": "439744a210e048f2b368abcc6babdf13", "links": {"self": {"href": "https://publications.scilifelab.se/publication/439744a210e048f2b368abcc6babdf13.json"}, "display": {"href": "https://publications.scilifelab.se/publication/439744a210e048f2b368abcc6babdf13"}}, "title": "Detoxified synthetic bacterial membrane vesicles as a vaccine platform against bacteria and SARS-CoV-2.", "authors": [{"family": "Park", "given": "Kyong-Su", "initials": "KS"}, {"family": "Svennerholm", "given": "Kristina", "initials": "K"}, {"family": "Crescitelli", "given": "Rossella", "initials": "R"}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C"}, {"family": "Gribonika", "given": "Inta", "initials": "I"}, {"family": "Andersson", "given": "Mickael", "initials": "M"}, {"family": "Bostr\u00f6m", "given": "Jonas", "initials": "J"}, {"family": "Alalam", "given": "Hanna", "initials": "H"}, {"family": "Harandi", "given": "Ali M", "initials": "AM"}, {"family": "Farewell", "given": "Anne", "initials": "A"}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J"}], "type": "journal article", "published": "2023-05-19", "journal": {"title": "J Nanobiotechnology", "issn": "1477-3155", "volume": "21", "issue": "1", "pages": "156", "issn-l": null}, "abstract": "The development of vaccines based on outer membrane vesicles (OMV) that naturally bud off from bacteria is an evolving field in infectious diseases. However, the inherent inflammatory nature of OMV limits their use as human vaccines. This study employed an engineered vesicle technology to develop synthetic bacterial vesicles (SyBV) that activate the immune system without the severe immunotoxicity of OMV. SyBV were generated from bacterial membranes through treatment with detergent and ionic stress. SyBV induced less inflammatory responses in macrophages and in mice compared to natural OMV. Immunization with SyBV or OMV induced comparable antigen-specific adaptive immunity. Specifically, immunization with Pseudomonas aeruginosa-derived SyBV protected mice against bacterial challenge, and this was accompanied by significant reduction in lung cell infiltration and inflammatory cytokines. Further, immunization with Escherichia coli-derived SyBV protected mice against E. coli sepsis, comparable to OMV-immunized group. The protective activity of SyBV was driven by the stimulation of B-cell and T-cell immunity. Also, SyBV were engineered to display the SARS-CoV-2 S1 protein on their surface, and these vesicles induced specific S1 protein antibody and T-cell responses. Collectively, these results demonstrate that SyBV may be a safe and efficient vaccine platform for the prevention of bacterial and viral infections.", "doi": "10.1186/s12951-023-01928-w", "pmid": "37208676", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service", "Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10196325"}, {"db": "pii", "key": "10.1186/s12951-023-01928-w"}], "notes": [], "created": "2023-12-01T10:49:33.099Z", "modified": "2024-01-16T13:46:27.495Z"}, {"entity": "publication", "iuid": "c81c05cd10ed48cf8f9ee510abbbe1ea", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c81c05cd10ed48cf8f9ee510abbbe1ea.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c81c05cd10ed48cf8f9ee510abbbe1ea"}}, "title": "Complement C3a treatment accelerates recovery after stroke via modulation of astrocyte reactivity and cortical connectivity.", "authors": [{"family": "Stokowska", "given": "Anna", "initials": "A"}, {"family": "Aswendt", "given": "Markus", "initials": "M"}, {"family": "Zucha", "given": "Daniel", "initials": "D"}, {"family": "Lohmann", "given": "Stephanie", "initials": "S"}, {"family": "Wieters", "given": "Frederique", "initials": "F"}, {"family": "Mor\u00e1n Suarez", "given": "Javier", "initials": "J"}, {"family": "Atkins", "given": "Alison L", "initials": "AL"}, {"family": "Li", "given": "YiXian", "initials": "Y"}, {"family": "Miteva", "given": "Maria", "initials": "M"}, {"family": "Lewin", "given": "Julia", "initials": "J"}, {"family": "Wiedermann", "given": "Dirk", "initials": "D"}, {"family": "Diedenhofen", "given": "Michael", "initials": "M"}, {"family": "Torinsson Naluai", "given": "\u00c5sa", "initials": "\u00c5"}, {"family": "Abaffy", "given": "Pavel", "initials": "P"}, {"family": "Valihrach", "given": "Lukas", "initials": "L"}, {"family": "Kubista", "given": "Mikael", "initials": "M"}, {"family": "Hoehn", "given": "Mathias", "initials": "M"}, {"family": "Pekny", "given": "Milos", "initials": "M"}, {"family": "Pekna", "given": "Marcela", "initials": "M"}], "type": "journal article", "published": "2023-05-15", "journal": {"title": "J. Clin. Invest.", "issn": "1558-8238", "volume": "133", "issue": "10", "issn-l": "0021-9738"}, "abstract": "Despite advances in acute care, ischemic stroke remains a major cause of long-term disability. Approaches targeting both neuronal and glial responses are needed to enhance recovery and improve long-term outcome. The complement C3a receptor (C3aR) is a regulator of inflammation with roles in neurodevelopment, neural plasticity, and neurodegeneration. Using mice lacking C3aR (C3aR-/-) and mice overexpressing C3a in the brain, we uncovered 2 opposing effects of C3aR signaling on functional recovery after ischemic stroke: inhibition in the acute phase and facilitation in the later phase. Peri-infarct astrocyte reactivity was increased and density of microglia reduced in C3aR-/- mice; C3a overexpression led to the opposite effects. Pharmacological treatment of wild-type mice with intranasal C3a starting 7 days after stroke accelerated recovery of motor function and attenuated astrocyte reactivity without enhancing microgliosis. C3a treatment stimulated global white matter reorganization, increased peri-infarct structural connectivity, and upregulated Igf1 and Thbs4 in the peri-infarct cortex. Thus, C3a treatment from day 7 after stroke exerts positive effects on astrocytes and neuronal connectivity while avoiding the deleterious consequences of C3aR signaling during the acute phase. Intranasal administration of C3aR agonists within a convenient time window holds translational promise to improve outcome after ischemic stroke.", "doi": "10.1172/JCI162253", "pmid": "36995772", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10178843"}, {"db": "pii", "key": "162253"}], "notes": [], "created": "2023-12-01T10:52:07.051Z", "modified": "2023-12-01T10:52:07.054Z"}, {"entity": "publication", "iuid": "0a4a4ff0ba344b0299aafc6757caac3e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0a4a4ff0ba344b0299aafc6757caac3e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0a4a4ff0ba344b0299aafc6757caac3e"}}, "title": "CRISPR-Cas9 knockout screen identifies novel treatment targets in childhood high-grade glioma.", "authors": [{"family": "Wenger", "given": "Anna", "initials": "A"}, {"family": "Karlsson", "given": "Ida", "initials": "I"}, {"family": "Kling", "given": "Teresia", "initials": "T"}, {"family": "Car\u00e9n", "given": "Helena", "initials": "H"}], "type": "journal article", "published": "2023-05-09", "journal": {"title": "Clin Epigenetics", "issn": "1868-7083", "volume": "15", "issue": "1", "pages": "80", "issn-l": "1868-7075"}, "abstract": "Brain tumours are the leading cause of cancer-related death in children, and there is no effective treatment. A growing body of evidence points to deregulated epigenetics as a tumour driver, particularly in paediatric cancers as they have relatively few genomic alterations, and key driver mutations have been identified in histone 3 (H3). Cancer stem cells (CSC) are implicated in tumour development, relapse and therapy resistance and thus particularly important to target. We therefore aimed to identify novel epigenetic treatment targets in CSC derived from H3-mutated high-grade glioma (HGG) through a CRISPR-Cas9 knockout screen.\n\nThe knockout screen identified more than 100 novel genes essential for the growth of CSC derived from paediatric HGG with H3K27M mutation. We successfully validated 12 of the 13 selected hits by individual knockout in the same two CSC lines, and for the top six hits we included two additional CSC lines derived from H3 wild-type paediatric HGG. Knockout of these genes led to a significant decrease in CSC growth, and altered stem cell and differentiation markers.\n\nThe screen robustly identified essential genes known in the literature, but also many novel genes essential for CSC growth in paediatric HGG. Six of the novel genes (UBE2N, CHD4, LSM11, KANSL1, KANSL3 and EED) were validated individually thus demonstrating their importance for CSC growth in H3-mutated and wild-type HGG. These genes should be further studied and evaluated as novel treatment targets in paediatric HGG.", "doi": "10.1186/s13148-023-01498-6", "pmid": "37161535", "labels": {"CRISPR Functional Genomics": "Service", "Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10170782"}, {"db": "pii", "key": "10.1186/s13148-023-01498-6"}], "notes": [], "created": "2023-09-18T16:49:06.034Z", "modified": "2023-12-01T10:52:32.572Z"}, {"entity": "publication", "iuid": "b0828736db78483ab5305cc2af46f22c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b0828736db78483ab5305cc2af46f22c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b0828736db78483ab5305cc2af46f22c"}}, "title": "Melanocortin-4 receptors on neurons in the parabrachial nucleus mediate inflammation-induced suppression of food-seeking behavior.", "authors": [{"family": "Shionoya", "given": "Kiseko", "initials": "K"}, {"family": "Nilsson", "given": "Anna", "initials": "A"}, {"family": "Engstr\u00f6m Ruud", "given": "Linda", "initials": "L"}, {"family": "Engblom", "given": "David", "initials": "D"}, {"family": "Blomqvist", "given": "Anders", "initials": "A"}], "type": "journal article", "published": "2023-05-00", "journal": {"title": "Brain, Behavior, and Immunity", "issn": "1090-2139", "volume": "110", "pages": "80-84", "issn-l": "0889-1591"}, "abstract": "Anorexia is a common symptom during infectious and inflammatory disease. Here we examined the role of melanocortin-4 receptors (MC4Rs) in inflammation-induced anorexia. Mice with transcriptional blockage of the MC4Rs displayed the same reduction of food intake following peripheral injection of lipopolysaccharide as wild type mice but were protected against the anorexic effect of the immune challenge in a test in which fasted animals were to use olfactory cues to find a hidden cookie. By using selective virus-mediated receptor re-expression we demonstrate that the suppression of the food-seeking behavior is subserved by MC4Rs in the brain stem parabrachial nucleus, a central hub for interoceptive information involved in the regulation of food intake. Furthermore, the selective expression of MC4R in the parabrachial nucleus also attenuated the body weight increase that characterizes MC4R KO mice. These data extend on the functions of the MC4Rs and show that MC4Rs in the parabrachial nucleus are critically involved in the anorexic response to peripheral inflammation but also contribute to body weight homeostasis during normal conditions.", "doi": "10.1016/j.bbi.2023.02.014", "pmid": "36813210", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S0889-1591(23)00039-9"}], "notes": [], "created": "2023-12-01T10:51:39.820Z", "modified": "2023-12-01T10:51:39.824Z"}, {"entity": "publication", "iuid": "02cf4d931b3848ceb099beb7b85e0436", "links": {"self": {"href": "https://publications.scilifelab.se/publication/02cf4d931b3848ceb099beb7b85e0436.json"}, "display": {"href": "https://publications.scilifelab.se/publication/02cf4d931b3848ceb099beb7b85e0436"}}, "title": "Investigating New Applications of a Photoswitchable Fluorescent Norbornadiene as a Multifunctional Probe for Delineation of Amyloid Plaque Polymorphism.", "authors": [{"family": "Dreos", "given": "Ambra", "initials": "A", "orcid": "0000-0003-0448-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/11d65a7542cd443982e123ab00d46e9a.json"}}, {"family": "Ge", "given": "Junyue", "initials": "J"}, {"family": "Najera", "given": "Francisco", "initials": "F", "orcid": "0000-0002-1635-5514", "researcher": {"href": "https://publications.scilifelab.se/researcher/59a60d855d794d45a9fff4746867037f.json"}}, {"family": "Tebikachew", "given": "Behabitu Ergette", "initials": "BE"}, {"family": "Perez-Inestrosa", "given": "Ezequiel", "initials": "E", "orcid": "0000-0001-7546-5273", "researcher": {"href": "https://publications.scilifelab.se/researcher/5ecc62575cbc43d9bfb86efd8299499c.json"}}, {"family": "Moth-Poulsen", "given": "Kasper", "initials": "K", "orcid": "0000-0003-4018-4927", "researcher": {"href": "https://publications.scilifelab.se/researcher/5807cc241ba24cf4a7841086d72dc3b9.json"}}, {"family": "Blennow", "given": "Kaj", "initials": "K"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H"}, {"family": "Hanrieder", "given": "J\u00f6rg", "initials": "J", "orcid": "0000-0001-6059-198X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e65454100674f98bf8f2575093f2441.json"}}], "type": "journal article", "published": "2023-04-28", "journal": {"title": "ACS Sens.", "issn": "2379-3694", "volume": "8", "issue": "4", "pages": "1500-1509", "issn-l": "2379-3694"}, "abstract": "Amyloid beta (A\u03b2) plaques are a major pathological hallmark of Alzheimer's disease (AD) and constitute of structurally heterogenic entities (polymorphs) that have been implicated in the phenotypic heterogeneity of AD pathology and pathogenesis. Understanding amyloid aggregation has been a critical limiting factor to gain understanding of AD pathogenesis, ultimately reflected in that the underlying mechanism remains elusive. We identified a fluorescent probe in the form of a turn-off photoswitchable norbornadiene derivative (NBD1) with several microenvironment-sensitive properties that make it relevant for applications within advanced fluorescence imaging, for example, multifunctional imaging. We explored the application of NBD1 for in situ delineation of structurally heterogenic A\u03b2 plaques in transgenic AD mouse models. NBD1 plaque imaging shows characteristic broader emission bands in the periphery and more narrow emission bands in the dense cores of mature cored plaques. Further, we demonstrate in situ photoisomerization of NBD1 to quadricyclane and thermal recovery in single plaques, which is relevant for applications within both functional and super-resolution imaging. This is the first time a norbornadiene photoswitch has been used as a probe for fluorescence imaging of A\u03b2 plaque pathology in situ and that its spectroscopic and switching properties have been studied within the specific environment of senile A\u03b2 plaques. These findings open the way toward new applications of NBD-based photoswitchable fluorescent probes for super-resolution or dual-color imaging and multifunctional microscopy of amyloid plaque heterogeneity. This could allow to visualize A\u03b2 plaques with resolution beyond the diffraction limit, label different plaque types, and gain insights into their physicochemical composition.", "doi": "10.1021/acssensors.2c02496", "pmid": "36946692", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10152485"}], "notes": [], "created": "2023-12-01T10:45:15.895Z", "modified": "2023-12-01T10:45:15.961Z"}, {"entity": "publication", "iuid": "be4e4a56967846f0956e28c676faae94", "links": {"self": {"href": "https://publications.scilifelab.se/publication/be4e4a56967846f0956e28c676faae94.json"}, "display": {"href": "https://publications.scilifelab.se/publication/be4e4a56967846f0956e28c676faae94"}}, "title": "Colorectal cancer-derived small extracellular vesicles induce TGF\u03b21-mediated epithelial to mesenchymal transition of hepatocytes.", "authors": [{"family": "Pucci", "given": "Marzia", "initials": "M"}, {"family": "Moschetti", "given": "Marta", "initials": "M"}, {"family": "Urz\u00ec", "given": "Ornella", "initials": "O"}, {"family": "Loria", "given": "Marco", "initials": "M"}, {"family": "Conigliaro", "given": "Alice", "initials": "A"}, {"family": "Di Bella", "given": "Maria Antonietta", "initials": "MA"}, {"family": "Crescitelli", "given": "Rossella", "initials": "R"}, {"family": "Olofsson Bagge", "given": "Roger", "initials": "R"}, {"family": "Gallo", "given": "Alessia", "initials": "A"}, {"family": "Santos", "given": "Mark F", "initials": "MF"}, {"family": "Puglisi", "given": "Caterina", "initials": "C"}, {"family": "Forte", "given": "Stefano", "initials": "S"}, {"family": "Lorico", "given": "Aurelio", "initials": "A"}, {"family": "Alessandro", "given": "Riccardo", "initials": "R"}, {"family": "Fontana", "given": "Simona", "initials": "S"}], "type": "journal article", "published": "2023-04-18", "journal": {"title": "Cancer Cell Int", "issn": "1475-2867", "volume": "23", "issue": "1", "pages": "77", "issn-l": "1475-2867"}, "abstract": "Metastatic disease is the major cause of cancer-related deaths. Increasing evidence shows that primary tumor cells can promote metastasis by preparing the local microenvironment of distant organs, inducing the formation of the so-called \"pre-metastatic niche\". In recent years, several studies have highlighted that among the tumor-derived molecular components active in pre-metastatic niche formation, small extracellular vesicles (sEVs) play a crucial role. Regarding liver metastasis, the ability of tumor-derived sEVs to affect the activities of non-parenchymal cells such as Kupffer cells and hepatic stellate cells is well described, while the effects on hepatocytes, the most conspicuous and functionally relevant hepatic cellular component, remain unknown.\n\nsEVs isolated from SW480 and SW620 CRC cells and from clinical samples of CRC patients and healthy subjects were used to treat human healthy hepatocytes (THLE-2 cells). RT-qPCR, Western blot and confocal microscopy were applied to investigate the effects of this treatment.\n\nOur study shows for the first time that TGF\u03b21-carrying CRC_sEVs impair the morphological and functional properties of healthy human hepatocytes by triggering their TGF\u03b21/SMAD-dependent EMT. These abilities of CRC_sEVs were further confirmed by evaluating the effects elicited on hepatocytes by sEVs isolated from plasma and biopsies from CRC patients.\n\nSince it is known that EMT of hepatocytes leads to the formation of a fibrotic environment, a well-known driver of metastasis, these results suggest that CRC_sEV-educated hepatocytes could have an active and until now neglected role during liver metastasis formation.", "doi": "10.1186/s12935-023-02916-8", "pmid": "37072829", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10114452"}, {"db": "pii", "key": "10.1186/s12935-023-02916-8"}], "notes": [], "created": "2023-12-01T10:50:00.517Z", "modified": "2023-12-01T10:50:00.520Z"}, {"entity": "publication", "iuid": "28c48d0c5e8c4da48d5fd6cb35eb4ef9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/28c48d0c5e8c4da48d5fd6cb35eb4ef9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/28c48d0c5e8c4da48d5fd6cb35eb4ef9"}}, "title": "Correlative Chemical Imaging and Spatial Chemometrics Delineate Alzheimer Plaque Heterogeneity at High Spatial Resolution.", "authors": [{"family": "Wehrli", "given": "Patrick M", "initials": "PM"}, {"family": "Ge", "given": "Junyue", "initials": "J"}, {"family": "Michno", "given": "Wojciech", "initials": "W"}, {"family": "Koutarapu", "given": "Srinivas", "initials": "S"}, {"family": "Dreos", "given": "Ambra", "initials": "A", "orcid": "0000-0003-0448-2089", "researcher": {"href": "https://publications.scilifelab.se/researcher/11d65a7542cd443982e123ab00d46e9a.json"}}, {"family": "Jha", "given": "Durga", "initials": "D"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H"}, {"family": "Blennow", "given": "Kaj", "initials": "K"}, {"family": "Hanrieder", "given": "J\u00f6rg", "initials": "J", "orcid": "0000-0001-6059-198X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e65454100674f98bf8f2575093f2441.json"}}], "type": "journal article", "published": "2023-03-27", "journal": {"title": "JACS Au", "issn": "2691-3704", "volume": "3", "issue": "3", "pages": "762-774", "issn-l": null}, "abstract": "We present a novel, correlative chemical imaging strategy based on multimodal matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI), hyperspectral microscopy, and spatial chemometrics. Our workflow overcomes challenges associated with correlative MSI data acquisition and alignment by implementing 1 + 1-evolutionary image registration for precise geometric alignment of multimodal imaging data and their integration in a common, truly multimodal imaging data matrix with maintained MSI resolution (10 \u03bcm). This enabled multivariate statistical modeling of multimodal imaging data using a novel multiblock orthogonal component analysis approach to identify covariations of biochemical signatures between and within imaging modalities at MSI pixel resolution. We demonstrate the method's potential through its application toward delineating chemical traits of Alzheimer's disease (AD) pathology. Here, trimodal MALDI MSI of transgenic AD mouse brain delineates beta-amyloid (A\u03b2) plaque-associated co-localization of lipids and A\u03b2 peptides. Finally, we establish an improved image fusion approach for correlative MSI and functional fluorescence microscopy. This allowed for high spatial resolution (300 nm) prediction of correlative, multimodal MSI signatures toward distinct amyloid structures within single plaque features critically implicated in A\u03b2 pathogenicity.", "doi": "10.1021/jacsau.2c00492", "pmid": "37006756", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10052239"}], "notes": [], "created": "2023-12-01T10:52:21.941Z", "modified": "2023-12-01T10:52:21.957Z"}, {"entity": "publication", "iuid": "a2c8a4d9ca4e4607a40342750b0dd092", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a2c8a4d9ca4e4607a40342750b0dd092.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a2c8a4d9ca4e4607a40342750b0dd092"}}, "title": "A proinsulin-dependent interaction between ENPL-1 and ASNA-1 in neurons is required to maintain insulin secretion in C. elegans.", "authors": [{"family": "Podraza-Farhanieh", "given": "Agnieszka", "initials": "A", "orcid": "0000-0002-1120-8216", "researcher": {"href": "https://publications.scilifelab.se/researcher/8244c5dad7974bc0a2a4ec38cc3e58ce.json"}}, {"family": "Raj", "given": "Dorota", "initials": "D", "orcid": "0000-0002-7357-2902", "researcher": {"href": "https://publications.scilifelab.se/researcher/23ff7c388c2b43e3a9d3a3514fe5e049.json"}}, {"family": "Kao", "given": "Gautam", "initials": "G", "orcid": "0000-0003-1313-3024", "researcher": {"href": "https://publications.scilifelab.se/researcher/4575b678a90740428136c9f5e1bdd53b.json"}}, {"family": "Naredi", "given": "Peter", "initials": "P", "orcid": "0000-0002-5652-0422", "researcher": {"href": "https://publications.scilifelab.se/researcher/a41ccd84008a4a94a29410451bc012c9.json"}}], "type": "journal article", "published": "2023-03-15", "journal": {"title": "Development", "issn": "1477-9129", "volume": "150", "issue": "6", "issn-l": "0950-1991"}, "abstract": "Neuropeptides, including insulin, are important regulators of physiological functions of the organisms. Trafficking through the Golgi is crucial for the regulation of secretion of insulin-like peptides. ASNA-1 (TRC40) and ENPL-1 (GRP94) are conserved insulin secretion regulators in Caenorhabditis elegans (and mammals), and mouse Grp94 mutants display type 2 diabetes. ENPL-1/GRP94 binds proinsulin and regulates proinsulin levels in C. elegans and mammalian cells. Here, we have found that ASNA-1 and ENPL-1 cooperate to regulate insulin secretion in worms via a physical interaction that is independent of the insulin-binding site of ENPL-1. The interaction occurs in DAF-28/insulin-expressing neurons and is sensitive to changes in DAF-28 pro-peptide levels. Consistently, ASNA-1 acted in neurons to promote DAF-28/insulin secretion. The chaperone form of ASNA-1 was likely the interaction partner of ENPL-1. Loss of asna-1 disrupted Golgi trafficking pathways. ASNA-1 localization to the Golgi was affected in enpl-1 mutants and ENPL-1 overexpression partially bypassed the ASNA-1 requirement. Taken together, we find a functional interaction between ENPL-1 and ASNA-1 that is necessary to maintain proper insulin secretion in C. elegans and provides insights into how their loss might cause diabetes in mammals.", "doi": "10.1242/dev.201035", "pmid": "36939052", "labels": {"Clinical Genomics Gothenburg": "Service", "Integrated Microscopy Technologies Gothenburg": "Service", "Glycoproteomics and MS Proteomics": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10112894"}, {"db": "pii", "key": "297263"}], "notes": [], "created": "2023-11-30T22:35:26.746Z", "modified": "2024-01-16T13:46:27.648Z"}, {"entity": "publication", "iuid": "e7b4dc14b96544fa94ff6365379352d7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e7b4dc14b96544fa94ff6365379352d7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e7b4dc14b96544fa94ff6365379352d7"}}, "title": "Tetramodal Chemical Imaging Delineates the Lipid-Amyloid Peptide Interplay at Single Plaques in Transgenic Alzheimer's Disease Models.", "authors": [{"family": "Ge", "given": "Junyue", "initials": "J"}, {"family": "Koutarapu", "given": "Srinivas", "initials": "S"}, {"family": "Jha", "given": "Durga", "initials": "D"}, {"family": "Dulewicz", "given": "Maciej", "initials": "M"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H"}, {"family": "Blennow", "given": "Kaj", "initials": "K"}, {"family": "Hanrieder", "given": "J\u00f6rg", "initials": "J", "orcid": "0000-0001-6059-198X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e65454100674f98bf8f2575093f2441.json"}}], "type": "journal article", "published": "2023-03-14", "journal": {"title": "Anal. Chem.", "issn": "1520-6882", "volume": "95", "issue": "10", "pages": "4692-4702", "issn-l": "0003-2700"}, "abstract": "Beta-amyloid (A\u03b2) plaque pathology is one of the most prominent histopathological feature of Alzheimer's disease (AD). The exact pathogenic mechanisms linking A\u03b2 to AD pathogenesis remain however not fully understood. Recent advances in amyloid-targeting pharmacotherapies highlight the critical relevance of A\u03b2 aggregation for understanding the molecular basis of AD pathogenesis. We developed a novel, integrated, tetramodal chemical imaging paradigm for acquisition of trimodal mass spectrometry imaging (MSI) and interlaced fluorescent microscopy from a single tissue section. We used this approach to comprehensively investigate lipid-A\u03b2 correlates at single plaques in two different mouse models of AD (tgAPPSwe and tgAPPArcSwe) with varying degrees of intrinsic properties affecting amyloid aggregation. Integration of the multimodal imaging data and multivariate data analysis identified characteristic patterns of plaque-associated lipid- and peptide localizations across both mouse models. Correlative fluorescence microscopy using structure-sensitive amyloid probes identified intra-plaque structure-specific lipid- and A\u03b2 patterns, including A\u03b2 1-40 and A\u03b2 1-42 along with gangliosides (GM), phosphoinositols (PI), conjugated ceramides (CerP and PE-Cer), and lysophospholipids (LPC, LPA, and LPI). Single plaque correlation analysis across all modalities further revealed how these distinct lipid species were associated with A\u03b2 peptide deposition across plaque heterogeneity, indicating different roles for those lipids in plaque growth and amyloid fibrillation, respectively. Here, conjugated ceramide species correlated with A\u03b2 core formation indicating their involvement in initial plaque seeding or amyloid maturation. In contrast, LPI and PI were solely correlated with general plaque growth. In addition, GM1 and LPC correlated with continuous A\u03b2 deposition and maturation. The results highlight the potential of this comprehensive multimodal imaging approach and implement distinct lipids in amyloidogenic proteinopathy.", "doi": "10.1021/acs.analchem.2c05302", "pmid": "36856542", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10018455"}], "notes": [], "created": "2023-12-01T10:45:31.081Z", "modified": "2023-12-01T10:45:31.090Z"}, {"entity": "publication", "iuid": "db921fadd3754d35903f60cecfb457ca", "links": {"self": {"href": "https://publications.scilifelab.se/publication/db921fadd3754d35903f60cecfb457ca.json"}, "display": {"href": "https://publications.scilifelab.se/publication/db921fadd3754d35903f60cecfb457ca"}}, "title": "Striking membrane defects in AdipoR-deficient cells.", "authors": [{"family": "Ruiz", "given": "Mario", "initials": "M"}, {"family": "Panagaki", "given": "Dimitra", "initials": "D"}, {"family": "H\u00f6\u00f6g", "given": "Johanna L", "initials": "JL"}, {"family": "Pilon", "given": "Marc", "initials": "M"}], "type": "journal article", "published": "2023-03-00", "journal": {"title": "J. Lipid Res.", "issn": "1539-7262", "volume": "64", "issue": "3", "pages": "100335", "issn-l": "0022-2275"}, "abstract": null, "doi": "10.1016/j.jlr.2023.100335", "pmid": "36682703", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9958347"}, {"db": "pii", "key": "S0022-2275(23)00008-1"}], "notes": [], "created": "2023-12-01T10:51:12.529Z", "modified": "2023-12-01T10:51:12.542Z"}, {"entity": "publication", "iuid": "56df3bb9232f4e88be8e1ffe8f4be0be", "links": {"self": {"href": "https://publications.scilifelab.se/publication/56df3bb9232f4e88be8e1ffe8f4be0be.json"}, "display": {"href": "https://publications.scilifelab.se/publication/56df3bb9232f4e88be8e1ffe8f4be0be"}}, "title": "Membrane permeability based on mesh analysis", "authors": [{"family": "Stenqvist", "given": "Bj\u00f6rn", "initials": "B", "orcid": "0000-0002-9099-0663", "researcher": {"href": "https://publications.scilifelab.se/researcher/8febbffefa8e4602af87ed8166b72de5.json"}}, {"family": "Ericson", "given": "Marica B", "initials": "MB", "orcid": "0000-0002-5987-5915", "researcher": {"href": "https://publications.scilifelab.se/researcher/af1f53e7cd234c36bdde7121e7204ed5.json"}}, {"family": "Gregoire", "given": "Sebastien", "initials": "S"}, {"family": "Biatry", "given": "Bruno", "initials": "B"}, {"family": "Cassin", "given": "Guillaume", "initials": "G"}, {"family": "Jankunec", "given": "Marija", "initials": "M"}, {"family": "Engblom", "given": "Johan", "initials": "J"}, {"family": "Sparr", "given": "Emma", "initials": "E", "orcid": "0000-0001-8343-9657", "researcher": {"href": "https://publications.scilifelab.se/researcher/7af3e5cb6d3a45fa888adad2fbaed1c2.json"}}], "type": "journal-article", "published": "2023-03-00", "journal": {"title": "Journal of Colloid and Interface Science", "issn": "0021-9797", "volume": "633", "pages": "526-535", "issn-l": null}, "abstract": null, "doi": "10.1016/j.jcis.2022.11.013", "pmid": "36463821", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2023-12-01T10:51:51.641Z", "modified": "2025-12-03T11:35:04.566Z"}, {"entity": "publication", "iuid": "d9e8f3f036e6405e9d013f0288d043d3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d9e8f3f036e6405e9d013f0288d043d3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d9e8f3f036e6405e9d013f0288d043d3"}}, "title": "Muc2-dependent microbial colonization of the jejunal mucus layer is diet sensitive and confers local resistance to enteric pathogen infection.", "authors": [{"family": "Birchenough", "given": "George M H", "initials": "GMH"}, {"family": "Schroeder", "given": "Bjoern O", "initials": "BO"}, {"family": "Sharba", "given": "Sinan", "initials": "S"}, {"family": "Arike", "given": "Liisa", "initials": "L"}, {"family": "Recktenwald", "given": "Christian V", "initials": "CV"}, {"family": "Pu\u00e9rtolas-Balint", "given": "Fabiola", "initials": "F"}, {"family": "Subramani", "given": "Mahadevan V", "initials": "MV"}, {"family": "Hansson", "given": "Karl T", "initials": "KT"}, {"family": "Yilmaz", "given": "Bahtiyar", "initials": "B"}, {"family": "Lind\u00e9n", "given": "Sara K", "initials": "SK"}, {"family": "B\u00e4ckhed", "given": "Fredrik", "initials": "F"}, {"family": "Hansson", "given": "Gunnar C", "initials": "GC"}], "type": "journal article", "published": "2023-02-28", "journal": {"title": "Cell Rep", "issn": "2211-1247", "volume": "42", "issue": "2", "pages": "112084", "issn-l": null}, "abstract": "Intestinal mucus barriers normally prevent microbial infections but are sensitive to diet-dependent changes in the luminal environment. Here we demonstrate that mice fed a Western-style diet (WSD) suffer regiospecific failure of the mucus barrier in the small intestinal jejunum caused by diet-induced mucus aggregation. Mucus barrier disruption due to either WSD exposure or chromosomal Muc2 deletion results in collapse of the commensal jejunal microbiota, which in turn sensitizes mice to atypical jejunal colonization by the enteric pathogen Citrobacter rodentium. We illustrate the jejunal mucus layer as a microbial habitat, and link the regiospecific mucus dependency of the microbiota to distinctive properties of the jejunal niche. Together, our data demonstrate a symbiotic mucus-microbiota relationship that normally prevents jejunal pathogen colonization, but is highly sensitive to disruption by exposure to a WSD.", "doi": "10.1016/j.celrep.2023.112084", "pmid": "36753416", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "mid", "key": "NIHMS1878880"}, {"db": "pmc", "key": "PMC10404306"}, {"db": "pii", "key": "S2211-1247(23)00095-5"}], "notes": [], "created": "2023-12-01T10:44:31.272Z", "modified": "2023-12-01T10:44:31.278Z"}, {"entity": "publication", "iuid": "9307e704e3a74ee58608adb1be1471ef", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9307e704e3a74ee58608adb1be1471ef.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9307e704e3a74ee58608adb1be1471ef"}}, "title": "A Novel and Functionally Diverse Class of Acetylcholine-Gated Ion Channels.", "authors": [{"family": "Hardege", "given": "Iris", "initials": "I", "orcid": "0000-0001-6063-5954", "researcher": {"href": "https://publications.scilifelab.se/researcher/a834728aae72483083e3727ba2523039.json"}}, {"family": "Morud", "given": "Julia", "initials": "J"}, {"family": "Courtney", "given": "Amy", "initials": "A"}, {"family": "Schafer", "given": "William R", "initials": "WR"}], "type": "journal article", "published": "2023-02-15", "journal": {"title": "J. Neurosci.", "issn": "1529-2401", "volume": "43", "issue": "7", "pages": "1111-1124", "issn-l": "0270-6474"}, "abstract": "Fast cholinergic neurotransmission is mediated by acetylcholine-gated ion channels; in particular, excitatory nicotinic acetylcholine receptors play well established roles in virtually all nervous systems. Acetylcholine-gated inhibitory channels have also been identified in some invertebrate phyla, yet their roles in the nervous system are less well understood. We report the existence of multiple new inhibitory ion channels with diverse ligand activation properties in Caenorhabditis elegans We identify three channels, LGC-40, LGC-57, and LGC-58, whose primary ligand is choline rather than acetylcholine, as well as the first evidence of a truly polymodal channel, LGC-39, which is activated by both cholinergic and aminergic ligands. Using our new ligand-receptor pairs we uncover the surprising extent to which single neurons in the hermaphrodite nervous system express both excitatory and inhibitory channels, not only for acetylcholine but also for the other major neurotransmitters. The results presented in this study offer new insight into the potential evolutionary benefit of a vast and diverse repertoire of ligand-gated ion channels to generate complexity in an anatomically compact nervous system.SIGNIFICANCE STATEMENT Here we describe the diversity of cholinergic signaling in the nematode Caenorhabditis elegans We identify and characterize a novel family of ligand-gated ion channels and show that they are preferentially gated by choline rather than acetylcholine and expressed broadly in the nervous system. Interestingly, we also identify one channel gated by chemically diverse ligands including acetylcholine and aminergic ligands. By using our new knowledge of these ligand-gated ion channels, we built a model to predict the synaptic polarity in the C. elegans connectome. This model can be used for generating hypotheses on neural circuit function.", "doi": "10.1523/JNEUROSCI.1516-22.2022", "pmid": "36604172", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9962794"}, {"db": "pii", "key": "JNEUROSCI.1516-22.2022"}], "notes": [], "created": "2023-12-01T10:46:20.194Z", "modified": "2023-12-01T10:46:20.230Z"}, {"entity": "publication", "iuid": "b806633fe59244ba83201a73b0a8fe68", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b806633fe59244ba83201a73b0a8fe68.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b806633fe59244ba83201a73b0a8fe68"}}, "title": "Ginsenoside Rg3 Reduces the Toxicity of Graphene Oxide Used for pH-Responsive Delivery of Doxorubicin to Liver and Breast Cancer Cells.", "authors": [{"family": "Rahimi", "given": "Shadi", "initials": "S", "orcid": "0000-0002-8376-9880", "researcher": {"href": "https://publications.scilifelab.se/researcher/df63c5c027c448e290f3d00f0173844a.json"}}, {"family": "van Leeuwen", "given": "Daniel", "initials": "D"}, {"family": "Roshanzamir", "given": "Fariba", "initials": "F", "orcid": "0000-0002-2424-761X", "researcher": {"href": "https://publications.scilifelab.se/researcher/e3a055ea38ce4fb2a569eb5f801de7e7.json"}}, {"family": "Pandit", "given": "Santosh", "initials": "S", "orcid": "0000-0002-8357-758X", "researcher": {"href": "https://publications.scilifelab.se/researcher/ef2b4388693848c68cf42174ddeb65be.json"}}, {"family": "Shi", "given": "Lei", "initials": "L"}, {"family": "Sasanian", "given": "Nima", "initials": "N"}, {"family": "Nielsen", "given": "Jens", "initials": "J"}, {"family": "Esbj\u00f6rner", "given": "Elin K", "initials": "EK"}, {"family": "Mijakovic", "given": "Ivan", "initials": "I", "orcid": "0000-0002-8860-6853", "researcher": {"href": "https://publications.scilifelab.se/researcher/c0e5dfcc215b494a860ca6d9254b0b56.json"}}], "type": "journal article", "published": "2023-01-24", "journal": {"title": "Pharmaceutics", "issn": "1999-4923", "volume": "15", "issue": "2", "issn-l": null}, "abstract": "Doxorubicin (DOX) is extensively used in chemotherapy, but it has serious side effects and is inefficient against some cancers, e.g., hepatocarcinoma. To ameliorate the delivery of DOX and reduce its side effects, we designed a pH-responsive delivery system based on graphene oxide (GO) that is capable of a targeted drug release in the acidic tumor microenvironment. GO itself disrupted glutathione biosynthesis and induced reactive oxygen species (ROS) accumulation in human cells. It induced IL17-directed JAK-STAT signaling and VEGF gene expression, leading to increased cell proliferation as an unwanted effect. To counter this, GO was conjugated with the antioxidant, ginsenoside Rg3, prior to loading with DOX. The conjugation of Rg3 to GO significantly reduced the toxicity of the GO carrier by abolishing ROS production. Furthermore, treatment of cells with GO-Rg3 did not induce IL17-directed JAK-STAT signaling and VEGF gene expression-nor cell proliferation-suggesting GO-Rg3 as a promising drug carrier. The anticancer activity of GO-Rg3-DOX conjugates was investigated against Huh7 hepatocarcinoma and MDA-MB-231 breast cancer cells. GO-Rg3-DOX conjugates significantly reduced cancer cell viability, primarily via downregulation of transcription regulatory genes and upregulation of apoptosis genes. GO-Rg3 is an effective, biocompatible, and pH responsive DOX carrier with potential to improve chemotherapy-at least against liver and breast cancers.", "doi": "10.3390/pharmaceutics15020391", "pmid": "36839713", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9965446"}, {"db": "pii", "key": "pharmaceutics15020391"}], "notes": [], "created": "2023-12-01T10:50:28.523Z", "modified": "2023-12-01T10:50:28.649Z"}, {"entity": "publication", "iuid": "1830a94c43ab4fb4bc9bd426ae087854", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1830a94c43ab4fb4bc9bd426ae087854.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1830a94c43ab4fb4bc9bd426ae087854"}}, "title": "Extracellular vesicle DNA from human melanoma tissues contains cancer-specific mutations.", "authors": [{"family": "Crescitelli", "given": "Rossella", "initials": "R"}, {"family": "Filges", "given": "Stefan", "initials": "S"}, {"family": "Karimi", "given": "Nasibeh", "initials": "N"}, {"family": "Urz\u00ec", "given": "Ornella", "initials": "O"}, {"family": "Alonso-Agudo", "given": "Tamara", "initials": "T"}, {"family": "St\u00e5hlberg", "given": "Anders", "initials": "A"}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J"}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C"}, {"family": "Olofsson Bagge", "given": "Roger", "initials": "R"}], "type": "journal article", "published": "2022-12-01", "journal": {"title": "Front Cell Dev Biol", "issn": "2296-634X", "volume": "10", "pages": "1028854", "issn-l": null}, "abstract": "Liquid biopsies are promising tools for early diagnosis and residual disease monitoring in patients with cancer, and circulating tumor DNA isolated from plasma has been extensively studied as it has been shown to contain tumor-specific mutations. Extracellular vesicles (EVs) present in tumor tissues carry tumor-derived molecules such as proteins and nucleic acids, and thus EVs can potentially represent a source of cancer-specific DNA. Here we identified the presence of tumor-specific DNA mutations in EVs isolated from six human melanoma metastatic tissues and compared the results with tumor tissue DNA and plasma DNA. Tumor tissue EVs were isolated using enzymatic treatment followed by ultracentrifugation and iodixanol density cushion isolation. A panel of 34 melanoma-related genes was investigated using ultra-sensitive sequencing (SiMSen-seq). We detected mutations in six genes in the EVs (BRAF, NRAS, CDKN2A, STK19, PPP6C, and RAC), and at least one mutation was detected in all melanoma EV samples. Interestingly, the mutant allele frequency was higher in DNA isolated from tumor-derived EVs compared to total DNA extracted directly from plasma DNA, supporting the potential role of tumor EVs as future biomarkers in melanoma.", "doi": "10.3389/fcell.2022.1028854", "pmid": "36531960", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9751452"}, {"db": "pii", "key": "1028854"}], "notes": [], "created": "2023-02-16T08:26:37.315Z", "modified": "2023-02-16T08:26:37.317Z"}, {"entity": "publication", "iuid": "afb17c9edcb7482db1d096b566ce536a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/afb17c9edcb7482db1d096b566ce536a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/afb17c9edcb7482db1d096b566ce536a"}}, "title": "Quantitative image analysis of protein foam microstructure and its correlation with rheological properties: Egg white foam", "authors": [{"family": "Bonilla", "given": "Jose C", "initials": "JC", "orcid": "0000-0001-8200-4918", "researcher": {"href": "https://publications.scilifelab.se/researcher/433c41fc62cd4ef1b2f6a5d8acc84cfd.json"}}, {"family": "S\u00f8rensen", "given": "Jesper L", "initials": "JL"}, {"family": "Warming", "given": "Amalie S", "initials": "AS", "orcid": "0000-0002-1708-3661", "researcher": {"href": "https://publications.scilifelab.se/researcher/bbc38b1bb9eb4d479524b4076b32445e.json"}}, {"family": "Clausen", "given": "Mathias P", "initials": "MP", "orcid": "0000-0003-1196-6241", "researcher": {"href": "https://publications.scilifelab.se/researcher/856a816bb2cb475e9c8dd112e3e5da31.json"}}], "type": "journal-article", "published": "2022-12-00", "journal": {"title": "Food Hydrocolloids", "issn": "0268-005X", "volume": "133", "pages": "108010", "issn-l": null}, "abstract": null, "doi": "10.1016/j.foodhyd.2022.108010", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Collaborative"}, "xrefs": [], "notes": [], "created": "2023-02-16T08:25:54.923Z", "modified": "2023-06-19T13:39:03.639Z"}, {"entity": "publication", "iuid": "8175d2c8812d4475a40501c87d36e35b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8175d2c8812d4475a40501c87d36e35b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8175d2c8812d4475a40501c87d36e35b"}}, "title": "Using reporters of different misfolded proteins reveals differential strategies in processing protein aggregates.", "authors": [{"family": "Schneider", "given": "Kara L", "initials": "KL"}, {"family": "Ahmadpour", "given": "Doryaneh", "initials": "D"}, {"family": "Keuenhof", "given": "Katharina S", "initials": "KS"}, {"family": "Eisele-B\u00fcrger", "given": "Anna Maria", "initials": "AM"}, {"family": "Berglund", "given": "Lisa Larsson", "initials": "LL"}, {"family": "Eisele", "given": "Frederik", "initials": "F"}, {"family": "Babazadeh", "given": "Roja", "initials": "R"}, {"family": "H\u00f6\u00f6g", "given": "Johanna L", "initials": "JL"}, {"family": "Nystr\u00f6m", "given": "Thomas", "initials": "T"}, {"family": "Widlund", "given": "Per O", "initials": "PO"}], "type": "journal article", "published": "2022-11-00", "journal": {"title": "J. Biol. Chem.", "issn": "1083-351X", "volume": "298", "issue": "11", "pages": "102476", "issn-l": "0021-9258"}, "abstract": "The accumulation of misfolded proteins is a hallmark of aging and many neurodegenerative diseases, making it important to understand how the cellular machinery recognizes and processes such proteins. A key question in this respect is whether misfolded proteins are handled in a similar way regardless of their genetic origin. To approach this question, we compared how three different misfolded proteins, guk1-7, gus1-3, and pro3-1, are handled by the cell. We show that all three are nontoxic, even though highly overexpressed, highlighting their usefulness in analyzing the cellular response to misfolding in the absence of severe stress. We found significant differences between the aggregation and disaggregation behavior of the misfolded proteins. Specifically, gus1-3 formed some aggregates that did not efficiently recruit the protein disaggregase Hsp104 and did not colocalize with the other misfolded reporter proteins. Strikingly, while all three misfolded proteins generally coaggregated and colocalized to specific sites in the cell, disaggregation was notably different; the rate of aggregate clearance of pro3-1 was faster than that of the other misfolded proteins, and its clearance rate was not hindered when pro3-1 colocalized with a slowly resolved misfolded protein. Finally, we observed using super-resolution light microscopy as well as immunogold labeling EM in which both showed an even distribution of the different misfolded proteins within an inclusion, suggesting that misfolding characteristics and remodeling, rather than spatial compartmentalization, allows for differential clearance of these misfolding reporters residing in the same inclusion. Taken together, our results highlight how properties of misfolded proteins can significantly affect processing.", "doi": "10.1016/j.jbc.2022.102476", "pmid": "36096201", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9636550"}, {"db": "pii", "key": "S0021-9258(22)00919-X"}], "notes": [], "created": "2023-02-16T08:26:24.796Z", "modified": "2023-02-16T08:26:24.810Z"}, {"entity": "publication", "iuid": "4a43a31c1f84404bb148ab52b6c5148e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4a43a31c1f84404bb148ab52b6c5148e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4a43a31c1f84404bb148ab52b6c5148e"}}, "title": "Chemical traits of cerebral amyloid angiopathy in familial British-, Danish-, and non-Alzheimer's dementias.", "authors": [{"family": "Michno", "given": "Wojciech", "initials": "W", "orcid": "0000-0002-3096-3604", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b4307eb6e45426e8176337e88c9c344.json"}}, {"family": "Koutarapu", "given": "Srinivas", "initials": "S"}, {"family": "Camacho", "given": "Rafael", "initials": "R", "orcid": "0000-0003-2325-6407", "researcher": {"href": "https://publications.scilifelab.se/researcher/6a7a8cfe28634821984b078ce3246343.json"}}, {"family": "Toomey", "given": "Christina", "initials": "C"}, {"family": "Stringer", "given": "Katie", "initials": "K"}, {"family": "Minta", "given": "Karolina", "initials": "K"}, {"family": "Ge", "given": "Junyue", "initials": "J"}, {"family": "Jha", "given": "Durga", "initials": "D"}, {"family": "Fernandez-Rodriguez", "given": "Julia", "initials": "J"}, {"family": "Brinkmalm", "given": "Gunnar", "initials": "G"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H", "orcid": "0000-0003-3930-4354", "researcher": {"href": "https://publications.scilifelab.se/researcher/85efee74eb4a4b38b63cf2823d204529.json"}}, {"family": "Blennow", "given": "Kaj", "initials": "K"}, {"family": "Ryan", "given": "Natalie S", "initials": "NS"}, {"family": "Lashley", "given": "Tammaryn", "initials": "T"}, {"family": "Hanrieder", "given": "J\u00f6rg", "initials": "J", "orcid": "0000-0001-6059-198X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e65454100674f98bf8f2575093f2441.json"}}], "type": "journal article", "published": "2022-11-00", "journal": {"title": "J. Neurochem.", "issn": "1471-4159", "volume": "163", "issue": "3", "pages": "233-246", "issn-l": "0022-3042"}, "abstract": "Familial British dementia (FBD) and familial Danish dementia (FDD) are autosomal dominant forms of dementia caused by mutations in the integral membrane protein 2B (ITM2B, also known as BRI2) gene. Secretase processing of mutant BRI2 leads to secretion and deposition of BRI2-derived amyloidogenic peptides, ABri and ADan that resemble APP/\u03b2-amyloid (A\u03b2) pathology, which is characteristic of Alzheimer's disease (AD). Amyloid pathology in FBD/FDD manifests itself predominantly in the microvasculature by ABri/ADan containing cerebral amyloid angiopathy (CAA). While ABri and ADan peptide sequences differ only in a few C-terminal amino acids, CAA in FDD is characterized by co-aggregation of ADan with A\u03b2, while in contrast no A\u03b2 deposition is observed in FBD. The fact that FDD patients display an earlier and more severe disease onset than FBD suggests a potential role of ADan and A\u03b2 co-aggregation that promotes a more rapid disease progression in FDD compared to FBD. It is therefore critical to delineate the chemical signatures of amyloid aggregation in these two vascular dementias. This in turn will increase the knowledge on the pathophysiology of these diseases and the pathogenic role of heterogenous amyloid peptide interactions and deposition, respectively. Herein, we used matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) in combination with hyperspectral, confocal microscopy based on luminescent conjugated oligothiophene probes (LCO) to delineate the structural traits and associated amyloid peptide patterns of single CAA in postmortem brain tissue of patients with FBD, FDD as well as sporadic CAA without AD (CAA+) that show pronounced CAA without parenchymal plaques. The results show that CAA in both FBD and FDD consist of N-terminally truncated- and pyroglutamate-modified amyloid peptide species (ADan and ABri), but that ADan peptides in FDD are also extensively C-terminally truncated as compared to ABri in FBD, which contributes to hydrophobicity of ADan species. Further, CAA in FDD showed co-deposition with A\u03b2 x-42 and A\u03b2 x-40 species. CAA+ vessels were structurally more mature than FDD/FBD CAA and contained significant amounts of pyroglutamated A\u03b2. When compared with FDD, A\u03b2 in CAA+ showed more C-terminal and less N-terminally truncations. In FDD, ADan showed spatial co-localization with A\u03b23pE-40 and A\u03b23-40 but not with A\u03b2x-42 species. This suggests an increased aggregation propensity of A\u03b2 in FDD that promotes co-aggregation of both A\u03b2 and ADan. Further, CAA maturity appears to be mainly governed by A\u03b2 content based on the significantly higher 500/580 patterns observed in CAA+ than in FDD and FBD, respectively. Together this is the first study of its kind on comprehensive delineation of Bri2 and APP-derived amyloid peptides in single vascular plaques in both FDD/FBD and sporadic CAA that provides new insight in non-AD-related vascular amyloid pathology. Cover Image for this issue: https://doi.org/10.1111/jnc.15424.", "doi": "10.1111/jnc.15694", "pmid": "36102248", "labels": {"Integrated Microscopy Technologies Gothenburg": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC9828067"}], "notes": [], "created": "2023-02-16T08:26:18.918Z", "modified": "2023-06-19T13:39:16.927Z"}, {"entity": "publication", "iuid": "7f8991eedf7e4aa7b95855a8d444544e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7f8991eedf7e4aa7b95855a8d444544e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7f8991eedf7e4aa7b95855a8d444544e"}}, "title": "Fecal luminal factors from patients with irritable bowel syndrome induce distinct gene expression of colonoids.", "authors": [{"family": "Iribarren", "given": "Cristina", "initials": "C", "orcid": "0000-0002-0632-7552", "researcher": {"href": "https://publications.scilifelab.se/researcher/81809ff8b0aa4eb2bd3cefdb75adc132.json"}}, {"family": "Nordlander", "given": "Sofia", "initials": "S", "orcid": "0000-0003-1353-3781", "researcher": {"href": "https://publications.scilifelab.se/researcher/035b6039e7924344a02772033b937823.json"}}, {"family": "Sundin", "given": "Johanna", "initials": "J", "orcid": "0000-0003-4713-1772", "researcher": {"href": "https://publications.scilifelab.se/researcher/dad18138b7bb460081b3f9538c193269.json"}}, {"family": "Isaksson", "given": "Stefan", "initials": "S"}, {"family": "Savolainen", "given": "Otto", "initials": "O"}, {"family": "T\u00f6rnblom", "given": "Hans", "initials": "H"}, {"family": "Magnusson", "given": "Maria K", "initials": "MK"}, {"family": "Simr\u00e9n", "given": "Magnus", "initials": "M"}, {"family": "\u00d6hman", "given": "Lena", "initials": "L", "orcid": "0000-0001-8142-2106", "researcher": {"href": "https://publications.scilifelab.se/researcher/79239c8719b24eba951c4e1702952d5e.json"}}], "type": "journal article", "published": "2022-10-00", "journal": {"title": "Neurogastroenterol. Motil.", "issn": "1365-2982", "issn-l": "1350-1925", "volume": "34", "issue": "10", "pages": "e14390"}, "abstract": "Alteration of the host-microbiota cross talk at the intestinal barrier may participate in the pathophysiology of irritable bowel syndrome (IBS). Therefore, we aimed to determine effects of fecal luminal factors from IBS patients on the colonic epithelium using colonoids.\r\n\r\nColon-derived organoid monolayers, colonoids, generated from a healthy subject, underwent stimulation with fecal supernatants from healthy subjects and IBS patients with predominant diarrhea, phosphate-buffered saline (PBS), or lipopolysaccharide (LPS). Cytokines in cell cultures and fecal LPS were measured by ELISA and mRNA gene expression of monolayers was analyzed using Qiagen RT2 Profiler PCR Arrays. The fecal microbiota profile was determined by the GA-map\u2122 dysbiosis test and the fecal metabolite profile was analyzed by untargeted liquid chromatography/mass spectrometry.\r\n\r\nColonoid monolayers stimulated with fecal supernatants from healthy subjects (n = 7), PBS (n = 4) or LPS (n = 3) presented distinct gene expression profiles, with some overlap (R2 Y = 0.70, Q2 = 0.43). Addition of fecal supernatants from healthy subjects and IBS patients (n = 9) gave rise to different gene expression profiles of the colonoid monolayers (R2 Y = 0.79, Q2 = 0.64). Genes (n = 22) related to immune response (CD1D, TLR5) and barrier integrity (CLDN15, DSC2) contributed to the separation. Levels of proinflammatory cytokines in colonoid monolayer cultures were comparable when stimulated with fecal supernatants from either donor types. Fecal microbiota and metabolite profiles, but not LPS content, differed between the study groups.\r\n\r\nFecal luminal factors from IBS patients induce a distinct colonic epithelial gene expression, potentially reflecting the disease pathophysiology. The culture of colonoids from healthy subjects with fecal supernatants from IBS patients may facilitate the exploration of IBS related intestinal micro-environmental and barrier interactions.", "doi": "10.1111/nmo.14390", "pmid": "35485994", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service", "Chalmers Mass Spectrometry Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9786662"}], "notes": [], "created": "2022-12-05T08:22:51.801Z", "modified": "2023-04-13T08:58:46.490Z"}, {"entity": "publication", "iuid": "d4607c3b5d1647179a3ed651e6923fa2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d4607c3b5d1647179a3ed651e6923fa2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d4607c3b5d1647179a3ed651e6923fa2"}}, "title": "Clearance of small intestinal crypts involves goblet cell mucus secretion by intracellular granule rupture and enterocyte ion transport.", "authors": [{"family": "Dolan", "given": "Brendan", "initials": "B", "orcid": "0000-0001-9062-3882", "researcher": {"href": "https://publications.scilifelab.se/researcher/6ff7d8f515ef4707ab6bca8da108f115.json"}}, {"family": "Ermund", "given": "Anna", "initials": "A", "orcid": "0000-0002-3233-043X", "researcher": {"href": "https://publications.scilifelab.se/researcher/8215eeb434f84deaafa2f9f198bfb2bc.json"}}, {"family": "Martinez-Abad", "given": "Beatriz", "initials": "B", "orcid": "0000-0002-0521-3473", "researcher": {"href": "https://publications.scilifelab.se/researcher/2d3781ca1b0245908c2030b4707cc34d.json"}}, {"family": "Johansson", "given": "Malin E V", "initials": "MEV", "orcid": "0000-0002-4237-6677", "researcher": {"href": "https://publications.scilifelab.se/researcher/520dab35c19049c8b3f1083a92e60d56.json"}}, {"family": "Hansson", "given": "Gunnar C", "initials": "GC", "orcid": "0000-0002-1900-1869", "researcher": {"href": "https://publications.scilifelab.se/researcher/44b3815603154322a6dac16f2fc1c1e9.json"}}], "type": "journal article", "published": "2022-09-20", "journal": {"title": "Sci Signal", "issn": "1937-9145", "volume": "15", "issue": "752", "pages": "eabl5848", "issn-l": "1945-0877"}, "abstract": "Goblet cells in the small intestinal crypts contain large numbers of mucin granules that are rapidly discharged to clean bacteria from the crypt. Because acetylcholine released by neuronal and nonneuronal cells controls many aspects of intestinal epithelial function, we used tissue explants and organoids to investigate the response of the small intestinal crypt to cholinergic stimulation. The activation of muscarinic acetylcholine receptors initiated a coordinated and rapid emptying of crypt goblet cells that flushed the crypt contents into the intestinal lumen. Cholinergic stimulation induced an expansion of the granule contents followed by intracellular rupture of the mucin granules. The mucus expanded intracellularly before the rupture of the goblet cell apical membrane and continued to expand after its release into the crypt lumen. The goblet cells recovered from membrane rupture and replenished their stores of mucin granules. Mucus secretion from the goblet cells depended on Ca2+ signaling and the expansion of the mucus in the crypt depended on gap junctions and on ion and water transport by enterocytes adjacent to the goblet cells. This distinctive mode of mucus secretion, which we refer to as \"expanding secretion,\" efficiently cleans the small intestine crypt through coordinated mucus, ion, and fluid secretion by goblet cells and enterocytes.", "doi": "10.1126/scisignal.abl5848", "pmid": "36126118", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "mid", "key": "NIHMS1851593"}, {"db": "pmc", "key": "PMC9749883"}], "notes": [], "created": "2023-02-16T08:26:10.686Z", "modified": "2023-02-16T08:26:10.773Z"}, {"entity": "publication", "iuid": "3ab6e9e3e50c4469b11e4b49e8ecad0b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3ab6e9e3e50c4469b11e4b49e8ecad0b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3ab6e9e3e50c4469b11e4b49e8ecad0b"}}, "title": "A small molecule screen for paqr-2 suppressors identifies Tyloxapol as a membrane fluidizer for C. elegans and mammalian cells.", "authors": [{"family": "Ruiz", "given": "Mario", "initials": "M"}, {"family": "Svensk", "given": "Emma", "initials": "E"}, {"family": "Einarsson", "given": "Elinor", "initials": "E"}, {"family": "Grahn", "given": "Erik Podda", "initials": "EP"}, {"family": "Pilon", "given": "Marc", "initials": "M"}], "type": "journal article", "published": "2022-09-01", "journal": {"title": "Biochimica et Biophysica Acta (BBA) - Biomembranes", "issn": "1879-2642", "volume": "1864", "issue": "9", "pages": "183959", "issn-l": "0005-2736"}, "abstract": "Defects in cell membrane homeostasis are implicated in numerous disorders, including cancer, neurodegeneration and diabetes. There is therefore a need for a powerful model to study membrane homeostasis and to identify eventual therapeutic routes. The C. elegans gene paqr-2 encodes a homolog of the mammalian AdipoR1 and AdipoR2 proteins that, when mutated, causes a membrane homeostasis defect accompanied by multiple phenotypes such as intolerance to dietary saturated fatty acids, intolerance to cold and a characteristic tail tip morphology defect. We screened a compound library to identify molecules that can suppress the paqr-2 phenotypes. A single positive hit, Tyloxapol, was found that very effectively suppresses multiple paqr-2 phenotypes. Tyloxapol is a non-ionic detergent currently in use clinically as an expectorant. Importantly, we examined the potential of Tyloxapol as a fluidizer in human cells and found that it improves the viability and membrane fluidity of AdipoR2-deficient human cells challenged with palmitic acid, a membrane-rigidifying saturated fatty acid.", "doi": "10.1016/j.bbamem.2022.183959", "pmid": "35588889", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S0005-2736(22)00098-0"}], "notes": [], "created": "2023-02-16T08:25:11.440Z", "modified": "2023-02-16T08:25:11.452Z"}, {"entity": "publication", "iuid": "d6f8fc37642e488783da206805ed9197", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d6f8fc37642e488783da206805ed9197.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d6f8fc37642e488783da206805ed9197"}}, "title": "Temporal brain transcriptome analysis reveals key pathological events after germinal matrix hemorrhage in neonatal rats.", "authors": [{"family": "Song", "given": "Juan", "initials": "J"}, {"family": "Nilsson", "given": "Gisela", "initials": "G"}, {"family": "Xu", "given": "Yiran", "initials": "Y"}, {"family": "Zelco", "given": "Aura", "initials": "A"}, {"family": "Rocha-Ferreira", "given": "Eridan", "initials": "E"}, {"family": "Wang", "given": "Yafeng", "initials": "Y"}, {"family": "Zhang", "given": "Xiaoli", "initials": "X"}, {"family": "Zhang", "given": "Shan", "initials": "S"}, {"family": "Ek", "given": "Joakim", "initials": "J"}, {"family": "Hagberg", "given": "Henrik", "initials": "H"}, {"family": "Zhu", "given": "Changlian", "initials": "C"}, {"family": "Wang", "given": "Xiaoyang", "initials": "X", "orcid": "0000-0001-9717-8160", "researcher": {"href": "https://publications.scilifelab.se/researcher/70fbed19bca84bec93f558168444227a.json"}}], "type": "journal article", "published": "2022-09-00", "journal": {"title": "J. Cereb. Blood Flow Metab.", "issn": "1559-7016", "volume": "42", "issue": "9", "pages": "1632-1649", "issn-l": "0271-678X"}, "abstract": "Germinal matrix hemorrhage (GMH) is a common complication in preterm infants and is associated with high risk of adverse neurodevelopmental outcomes. We used a rat GMH model and performed RNA sequencing to investigate the signaling pathways and biological processes following hemorrhage. GMH induced brain injury characterized by early hematoma and subsequent tissue loss. At 6 hours after GMH, gene expression indicated an increase in mitochondrial activity such as ATP metabolism and oxidative phosphorylation along with upregulation of cytoprotective pathways and heme metabolism. At 24 hours after GMH, the expression pattern suggested an increase in cell cycle progression and downregulation of neurodevelopmental-related pathways. At 72 hours after GMH, there was an increase in genes related to inflammation and an upregulation of ferroptosis. Hemoglobin components and genes related to heme metabolism and ferroptosis such as Hmox1, Alox15, and Alas2 were among the most upregulated genes. We observed dysregulation of processes involved in development, mitochondrial function, cholesterol biosynthesis, and inflammation, all of which contribute to neurodevelopmental deterioration following GMH. This study is the first temporal transcriptome profile providing a comprehensive overview of the molecular mechanisms underlying brain injury following GMH, and it provides useful guidance in the search for therapeutic interventions.", "doi": "10.1177/0271678X221098811", "pmid": "35491813", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9441725"}], "notes": [], "created": "2023-02-16T08:25:37.304Z", "modified": "2023-02-16T08:25:37.329Z"}, {"entity": "publication", "iuid": "e85aac1ccfe44c689708ad7b122acfa4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e85aac1ccfe44c689708ad7b122acfa4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e85aac1ccfe44c689708ad7b122acfa4"}}, "title": "Genetically controlled mtDNA deletions prevent ROS damage by arresting oxidative phosphorylation.", "authors": [{"family": "Stenberg", "given": "Simon", "initials": "S", "orcid": "0000-0003-0300-1730", "researcher": {"href": "https://publications.scilifelab.se/researcher/d59ba977fddf4071928bca5fdfc04ba2.json"}}, {"family": "Li", "given": "Jing", "initials": "J"}, {"family": "Gjuvsland", "given": "Arne B", "initials": "AB"}, {"family": "Persson", "given": "Karl", "initials": "K"}, {"family": "Demitz-Helin", "given": "Erik", "initials": "E"}, {"family": "Gonz\u00e1lez Pe\u00f1a", "given": "Carles", "initials": "C", "orcid": "0000-0002-7771-7988", "researcher": {"href": "https://publications.scilifelab.se/researcher/e92cd4ba564e4d0999681bf59cc95c70.json"}}, {"family": "Yue", "given": "Jia-Xing", "initials": "JX", "orcid": "0000-0002-2122-9221", "researcher": {"href": "https://publications.scilifelab.se/researcher/9c17dbcd3dff4f61aed7cc85a3a7136a.json"}}, {"family": "Gilchrist", "given": "Ciaran", "initials": "C"}, {"family": "\u00c4reng\u00e5rd", "given": "Timmy", "initials": "T"}, {"family": "Ghiaci", "given": "Payam", "initials": "P"}, {"family": "Larsson-Berglund", "given": "Lisa", "initials": "L"}, {"family": "Zackrisson", "given": "Martin", "initials": "M"}, {"family": "Smits", "given": "Silvana", "initials": "S"}, {"family": "Hallin", "given": "Johan", "initials": "J"}, {"family": "H\u00f6\u00f6g", "given": "Johanna L", "initials": "JL", "orcid": "0000-0003-2162-3816", "researcher": {"href": "https://publications.scilifelab.se/researcher/f1eaedff964f4060ae6e69f59cad4521.json"}}, {"family": "Molin", "given": "Mikael", "initials": "M", "orcid": "0000-0002-3903-8503", "researcher": {"href": "https://publications.scilifelab.se/researcher/12e9dc11d1b047d88913ea3bcb2694be.json"}}, {"family": "Liti", "given": "Gianni", "initials": "G", "orcid": "0000-0002-2318-0775", "researcher": {"href": "https://publications.scilifelab.se/researcher/96fb0b05418743bc9966610ff45a3220.json"}}, {"family": "Omholt", "given": "Stig W", "initials": "SW", "orcid": "0000-0002-8320-4337", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a0f2458dfa64ac09c95356b1baf9f55.json"}}, {"family": "Warringer", "given": "Jonas", "initials": "J", "orcid": "0000-0001-6144-2740", "researcher": {"href": "https://publications.scilifelab.se/researcher/864cb0fde85a4aaeb68627f67e97d283.json"}}], "type": "journal article", "published": "2022-07-08", "journal": {"title": "Elife", "issn": "2050-084X", "volume": "11", "issn-l": "2050-084X"}, "abstract": "Deletion of mitochondrial DNA in eukaryotes is currently attributed to rare accidental events associated with mitochondrial replication or repair of double-strand breaks. We report the discovery that yeast cells arrest harmful intramitochondrial superoxide production by shutting down respiration through genetically controlled deletion of mitochondrial oxidative phosphorylation genes. We show that this process critically involves the antioxidant enzyme superoxide dismutase 2 and two-way mitochondrial-nuclear communication through Rtg2 and Rtg3. While mitochondrial DNA homeostasis is rapidly restored after cessation of a short-term superoxide stress, long-term stress causes maladaptive persistence of the deletion process, leading to complete annihilation of the cellular pool of intact mitochondrial genomes and irrevocable loss of respiratory ability. This shows that oxidative stress-induced mitochondrial impairment may be under strict regulatory control. If the results extend to human cells, the results may prove to be of etiological as well as therapeutic importance with regard to age-related mitochondrial impairment and disease.", "doi": "10.7554/eLife.76095", "pmid": "35801695", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9427111"}, {"db": "pii", "key": "76095"}], "notes": [], "created": "2023-02-16T08:26:04.422Z", "modified": "2023-02-16T08:26:04.606Z"}, {"entity": "publication", "iuid": "f1346c6cd8c840368959ca118d65ec12", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f1346c6cd8c840368959ca118d65ec12.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f1346c6cd8c840368959ca118d65ec12"}}, "title": "Characterization of Decellularized Implants for Extracellular Matrix Integrity and Immune Response Elicitation.", "authors": [{"family": "Banerjee", "given": "Debashish", "initials": "D", "orcid": "0000-0002-7270-5793", "researcher": {"href": "https://publications.scilifelab.se/researcher/b2d42ae487cd4a3c93e6d3ab854f4fb3.json"}}, {"family": "Nayakawde", "given": "Nikhil B", "initials": "NB"}, {"family": "Antony", "given": "Deepti", "initials": "D"}, {"family": "Deshmukh", "given": "Meghshree", "initials": "M"}, {"family": "Ghosh", "given": "Sudip", "initials": "S"}, {"family": "Sihlbom", "given": "Carina", "initials": "C"}, {"family": "Berger", "given": "Evelin", "initials": "E"}, {"family": "Ul Haq", "given": "Uzair", "initials": "U"}, {"family": "Olausson", "given": "Michael", "initials": "M", "orcid": "0000-0002-3949-9430", "researcher": {"href": "https://publications.scilifelab.se/researcher/22b9e4faaf144faaa22cbf9dc4f521d9.json"}}], "type": "journal article", "published": "2022-07-00", "journal": {"title": "Tissue Eng Part A", "issn": "1937-335X", "issn-l": null, "volume": "28", "issue": "13-14", "pages": "621-639"}, "abstract": "Biological scaffold is a popular choice for the preparation of tissue-engineered organs and has the potential to address donor shortages in clinics. However, biological scaffolds prepared by physical or chemical agents cause damage to the extracellular matrix (ECM) by potentially inducing immune responses after implantation. The current study explores the fate of the decellularized (DC) scaffolds using a cocktail of chemicals following implantation without using immunosuppressants. Using the syngeneic (Lewis male-Lewis female) and allogeneic (Brown Norway male-Lewis female) models and different tissue routes (subcutaneous vs. omentum) for implantation, we applied in-depth quantitative proteomics, genomics along with histology and quantitative image analysis tools to comprehensively describe and compare the proteins following DC and postimplantation. Our data helped to identify any alteration postdecullarization as well implantation. We could also monitor route-specific modulation of the ECM and regulation of the immune responses (macrophage and T cells) following implantation. The current approach opens up the possibility to monitor the fate of biological scaffolds in terms of the ECM and immune response against the implants. In addition, the identification of different routes helped us to identify differential immune responses against the implants. This study opens up the potential to identify the changes associated with chemical DC both pre- and postimplantation, which could further help to promote research in this direction. Impact Statement The development of a biological scaffold helps in the preparation of a functional organ in the clinics. In the current study, we develop a strategy for chemical decellularization and explored two different routes to understand the differential responses elicited postimplantation. The use of sensitive protein and genomic tools to study the changes creates a favorable environment for similar efforts to develop and characterize biological scaffolds before further trials in the clinics. The current study, which was carried out without any immunosuppressive agents, could help to establish (a) appropriate chemical strategies for preparing biological scaffolds as well as (b) identify putative implantable routes to circumvent any adverse immune reactions, which will ultimately decide the outcome for acceptance or rejection of the scaffold/implant.", "doi": "10.1089/ten.TEA.2021.0146", "pmid": "34963315", "labels": {"Integrated Microscopy Technologies Gothenburg": "Collaborative", "Glycoproteomics and MS Proteomics": "Collaborative"}, "xrefs": [], "notes": [], "created": "2023-02-16T08:15:11.058Z", "modified": "2024-01-16T13:46:28.883Z"}, {"entity": "publication", "iuid": "c3b8d4d3c3484613b133d6973c075339", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c3b8d4d3c3484613b133d6973c075339.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c3b8d4d3c3484613b133d6973c075339"}}, "title": "Non-coding 7S RNA inhibits transcription via mitochondrial RNA polymerase dimerization.", "authors": [{"family": "Zhu", "given": "Xuefeng", "initials": "X"}, {"family": "Xie", "given": "Xie", "initials": "X"}, {"family": "Das", "given": "Hrishikesh", "initials": "H"}, {"family": "Tan", "given": "Benedict G", "initials": "BG"}, {"family": "Shi", "given": "Yonghong", "initials": "Y"}, {"family": "Al-Behadili", "given": "Ali", "initials": "A"}, {"family": "Peter", "given": "Bradley", "initials": "B"}, {"family": "Motori", "given": "Elisa", "initials": "E"}, {"family": "Valenzuela", "given": "Sebastian", "initials": "S"}, {"family": "Posse", "given": "Viktor", "initials": "V"}, {"family": "Gustafsson", "given": "Claes M", "initials": "CM"}, {"family": "H\u00e4llberg", "given": "B Martin", "initials": "BM"}, {"family": "Falkenberg", "given": "Maria", "initials": "M"}], "type": "journal article", "published": "2022-06-23", "journal": {"title": "Cell", "issn": "1097-4172", "volume": "185", "issue": "13", "pages": "2309-2323.e24", "issn-l": "0092-8674"}, "abstract": "The mitochondrial genome encodes 13 components of the oxidative phosphorylation system, and altered mitochondrial transcription drives various human pathologies. A polyadenylated, non-coding RNA molecule known as 7S RNA is transcribed from a region immediately downstream of the light strand promoter in mammalian cells, and its levels change rapidly in response to physiological conditions. Here, we report that 7S RNA has a regulatory function, as it controls levels of mitochondrial transcription both in vitro and in cultured human cells. Using cryo-EM, we show that POLRMT dimerization is induced by interactions with 7S RNA. The resulting POLRMT dimer interface sequesters domains necessary for promoter recognition and unwinding, thereby preventing transcription initiation. We propose that the non-coding 7S RNA molecule is a component of a negative feedback loop that regulates mitochondrial transcription in mammalian cells.", "doi": "10.1016/j.cell.2022.05.006", "pmid": "35662414", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S0092-8674(22)00590-6"}], "notes": [], "created": "2023-02-16T08:25:44.143Z", "modified": "2023-02-16T08:25:44.147Z"}, {"entity": "publication", "iuid": "ac8958e2f62b4464bbb943d051ebf9c3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ac8958e2f62b4464bbb943d051ebf9c3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ac8958e2f62b4464bbb943d051ebf9c3"}}, "title": "Orthotopic Transplantation of Human Paediatric High-Grade Glioma in Zebrafish Larvae.", "authors": [{"family": "Larsson", "given": "Susanna", "initials": "S"}, {"family": "Kettunen", "given": "Petronella", "initials": "P", "orcid": "0000-0002-2510-3423", "researcher": {"href": "https://publications.scilifelab.se/researcher/4531ee4b5fc34768bfbae2d2fa22e8f8.json"}}, {"family": "Car\u00e9n", "given": "Helena", "initials": "H", "orcid": "0000-0002-8584-555X", "researcher": {"href": "https://publications.scilifelab.se/researcher/b31c235b05d54d5ab5d65b3e640c9f66.json"}}], "type": "journal article", "published": "2022-05-10", "journal": {"title": "Brain Sci", "issn": "2076-3425", "volume": "12", "issue": "5", "issn-l": "2076-3425"}, "abstract": "Brain tumours are the most common cause of death among children with solid tumours, and high-grade gliomas (HGG) are among the most devastating forms with very poor outcomes. In the search for more effective treatments for paediatric HGG, there is a need for better experimental models. To date, there are no xenograft zebrafish models developed for human paediatric HGG; existing models rely on adult cells. The use of paediatric models is of great importance since it is well known that the genetic and epigenetic mechanisms behind adult and paediatric disease differ greatly. In this study, we present a clinically relevant in vivo model based on paediatric primary glioma stem cell (GSC) cultures, which after orthotopic injection into the zebrafish larvae, can be monitored using confocal imaging over time. We show that cells invade the brain tissue and can be followed up to 8 days post-injection while they establish in the fore/mid brain. This model offers an in vivo system where tumour invasion can be monitored and drug treatments quickly be evaluated. The possibility to monitor patient-specific cells has the potential to contribute to a better understanding of cellular behaviour and personalised treatments in the future.", "doi": "10.3390/brainsci12050625", "pmid": "35625011", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9139401"}, {"db": "pii", "key": "brainsci12050625"}], "notes": [], "created": "2023-02-16T08:24:34.946Z", "modified": "2023-02-16T08:24:35.001Z"}, {"entity": "publication", "iuid": "ce0f7b27e88b45078db3fbf46d71516b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ce0f7b27e88b45078db3fbf46d71516b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ce0f7b27e88b45078db3fbf46d71516b"}}, "title": "A Fatty Diet Induces a Jejunal Ketogenesis Which Inhibits Local SGLT1-Based Glucose Transport via an Acetylation Mechanism-Results from a Randomized Cross-Over Study between Iso-Caloric High-Fat versus High-Carbohydrate Diets in Healthy Volunteers.", "authors": [{"family": "Elebring", "given": "Erik", "initials": "E"}, {"family": "Wallenius", "given": "Ville", "initials": "V", "orcid": "0000-0001-8668-3196", "researcher": {"href": "https://publications.scilifelab.se/researcher/e728cf3f550046a590066de0e0cd47aa.json"}}, {"family": "Casselbrant", "given": "Anna", "initials": "A", "orcid": "0000-0001-7514-7435", "researcher": {"href": "https://publications.scilifelab.se/researcher/994b2b65cd154b359f5228eb0c69828b.json"}}, {"family": "Docherty", "given": "Neil G", "initials": "NG"}, {"family": "Roux", "given": "Carel W le", "initials": "CWL", "orcid": "0000-0001-5521-5445", "researcher": {"href": "https://publications.scilifelab.se/researcher/3def373e973945889670140361ad8ee5.json"}}, {"family": "Marschall", "given": "Hanns-Ulrich", "initials": "HU", "orcid": "0000-0001-7347-3085", "researcher": {"href": "https://publications.scilifelab.se/researcher/82b16fa78a994d12bd49ed280012893c.json"}}, {"family": "F\u00e4ndriks", "given": "Lars", "initials": "L", "orcid": "0000-0003-0736-3034", "researcher": {"href": "https://publications.scilifelab.se/researcher/32daf05ef1f541cbbdf0b4de2fbd142e.json"}}], "type": "journal article", "published": "2022-05-07", "journal": {"title": "Nutrients", "issn": "2072-6643", "volume": "14", "issue": "9", "issn-l": "2072-6643"}, "abstract": "Insights into the nature of gut adaptation after different diets enhance the understanding of how food modifications can be used to treat type 2 diabetes and obesity. The aim was to understand how diets, enriched in fat or carbohydrates, affect glucose absorption in the human healthy jejunum, and what mechanisms are involved.\n\nFifteen healthy subjects received, in randomised order and a crossover study design, two weeks of iso-caloric high-fat diet (HFD) and high-carbohydrate diet (HCD). Following each dietary period, jejunal mucosa samples were retrieved and assessed for protein expression using immunofluorescence and western blotting. Functional characterisation of epithelial glucose transport was assessed ex vivo using Ussing chambers. Regulation of SGLT1 through histone acetylation was studied in vitro in Caco-2 and human jejunal enteroid monolayer cultures.\n\nHFD, compared to HCD, decreased jejunal Ussing chamber epithelial glucose transport and the expression of apical transporters for glucose (SGLT1) and fructose (GLUT5), while expression of the basolateral glucose transporter GLUT2 was increased. HFD also increased protein expression of the ketogenesis rate-limiting enzyme mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) and decreased the acetylation of histone 3 at lysine 9 (H3K9ac). Studies in Caco-2 and human jejunal enteroid monolayer cultures indicated a ketogenesis-induced activation of sirtuins, in turn decreasing SGLT1 expression.\n\nJejunal glucose absorption is decreased by a fat-enriched diet, via a ketogenesis-induced alteration of histone acetylation responsible for the silencing of SGLT1 transcription. The work relates to a secondary outcome in ClinicalTrials.gov (NCT02088853).", "doi": "10.3390/nu14091961", "pmid": "35565929", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9100393"}, {"db": "pii", "key": "nu14091961"}, {"db": "ClinicalTrials.gov", "key": "NCT02088853"}], "notes": [], "created": "2023-02-16T08:23:40.094Z", "modified": "2023-02-16T08:23:40.167Z"}, {"entity": "publication", "iuid": "26a8fd95b6b245deaf4f5e8e84b339a7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/26a8fd95b6b245deaf4f5e8e84b339a7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/26a8fd95b6b245deaf4f5e8e84b339a7"}}, "title": "Mechanical removal of biofilm on titanium discs: An in vitro study.", "authors": [{"family": "Ichioka", "given": "Yuki", "initials": "Y", "orcid": "0000-0003-0318-3167", "researcher": {"href": "https://publications.scilifelab.se/researcher/6de60717a790425a9304a30b8e2bc34e.json"}}, {"family": "Derks", "given": "Jan", "initials": "J", "orcid": "0000-0002-1133-6074", "researcher": {"href": "https://publications.scilifelab.se/researcher/459abeceb7c24480af9f0a444f3edd81.json"}}, {"family": "Dahl\u00e9n", "given": "Gunnar", "initials": "G"}, {"family": "Berglundh", "given": "Tord", "initials": "T", "orcid": "0000-0001-5864-6398", "researcher": {"href": "https://publications.scilifelab.se/researcher/2d29bd79b2914b47b00a0c1005b30b43.json"}}, {"family": "Larsson", "given": "Lena", "initials": "L"}], "type": "journal article", "published": "2022-05-00", "journal": {"title": "J. Biomed. Mater. Res. Part B Appl. Biomater.", "issn": "1552-4981", "volume": "110", "issue": "5", "pages": "1044-1055", "issn-l": "1552-4973"}, "abstract": "The objective of this in vitro study was to evaluate surface cleanness and cytocompatibility following mechanical instrumentation of biofilm-contaminated titanium surfaces. Titanium discs (non-modified [Ti(s)] and shot-blasted surfaces [Ti(r)]) contaminated with Streptococcus gordonii were instrumented using four different techniques: (i) gauze soaked in saline (GS), (ii) ultra-sonic device (US), (iii) rotating nickel-titanium brush (TiB), or (iv) air-polishing device (AP). Non-contaminated, untreated titanium disks were used as controls (C). Residual deposits and cytocompatibility for osteoblast-like cells were evaluated using scanning electron microscopy, immunofluorescence, and reverse transcriptase polymerase chain reaction. While the number of residual bacteria on Ti(s) discs was close to 0 in all treatment groups, significantly higher mean numbers of residual bacteria were observed on Ti(r) discs for GS (152.7 \u00b1 75.7) and TiB (33.5 \u00b1 22.2) than for US (0) and AP (0). Instrumentation with US resulted in deposition of foreign material (mean area% of foreign material: 3.0 \u00b1 3.6% and 10.8 \u00b1 9.6% for Ti(s) and Ti(r) discs, respectively). AP was the most effective decontamination procedure in reducing bacteria without depositing residual foreign material on Ti(r) discs. TiB and AP were superior methods in restoring cytocompatibility, although no method of mechanical decontamination resulted in pristine levels of cytocompatibility.", "doi": "10.1002/jbm.b.34978", "pmid": "34897974", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2023-02-16T08:24:12.480Z", "modified": "2023-02-16T08:24:12.581Z"}, {"entity": "publication", "iuid": "237d4257446a41e89c2141735913e512", "links": {"self": {"href": "https://publications.scilifelab.se/publication/237d4257446a41e89c2141735913e512.json"}, "display": {"href": "https://publications.scilifelab.se/publication/237d4257446a41e89c2141735913e512"}}, "title": "Induction of Mitochondrial Fragmentation and Mitophagy after Neonatal Hypoxia-Ischemia.", "authors": [{"family": "Nair", "given": "Syam", "initials": "S", "orcid": "0000-0001-8470-2162", "researcher": {"href": "https://publications.scilifelab.se/researcher/733eacd288ce4eefaad48c391436a319.json"}}, {"family": "Leverin", "given": "Anna-Lena", "initials": "AL"}, {"family": "Rocha-Ferreira", "given": "Eridan", "initials": "E", "orcid": "0000-0002-9342-4691", "researcher": {"href": "https://publications.scilifelab.se/researcher/9c297cd7e1a3447aa61e5faddcb90693.json"}}, {"family": "Sobotka", "given": "Kristina S", "initials": "KS"}, {"family": "Thornton", "given": "Claire", "initials": "C", "orcid": "0000-0001-7676-3272", "researcher": {"href": "https://publications.scilifelab.se/researcher/80dc80b67a7c4b949318e1f5aa2666f9.json"}}, {"family": "Mallard", "given": "Carina", "initials": "C", "orcid": "0000-0001-8953-919X", "researcher": {"href": "https://publications.scilifelab.se/researcher/2d0fa7de10554b5bb5a0e1ee64902aa1.json"}}, {"family": "Hagberg", "given": "Henrik", "initials": "H"}], "type": "journal article", "published": "2022-04-01", "journal": {"title": "Cells", "issn": "2073-4409", "volume": "11", "issue": "7", "issn-l": "2073-4409"}, "abstract": "Hypoxia-ischemia (HI) leads to immature brain injury mediated by mitochondrial stress. If damaged mitochondria cannot be repaired, mitochondrial permeabilization ensues, leading to cell death. Non-optimal turnover of mitochondria is critical as it affects short and long term structural and functional recovery and brain development. Therefore, disposal of deficient mitochondria via mitophagy and their replacement through biogenesis is needed. We utilized mt-Keima reporter mice to quantify mitochondrial morphology (fission, fusion) and mitophagy and their mechanisms in primary neurons after Oxygen Glucose Deprivation (OGD) and in brain sections after neonatal HI. Molecular mechanisms of PARK2-dependent and -independent pathways of mitophagy were investigated in vivo by PCR and Western blotting. Mitochondrial morphology and mitophagy were investigated using live cell microscopy. In primary neurons, we found a primary fission wave immediately after OGD with a significant increase in mitophagy followed by a secondary phase of fission at 24 h following recovery. Following HI, mitophagy was upregulated immediately after HI followed by a second wave at 7 days. Western blotting suggests that both PINK1/Parkin-dependent and -independent mechanisms, including NIX and FUNDC1, were upregulated immediately after HI, whereas a PINK1/Parkin mechanism predominated 7 days after HI. We hypothesize that excessive mitophagy in the early phase is a pathologic response which may contribute to secondary energy depletion, whereas secondary mitophagy may be involved in post-HI regeneration and repair.", "doi": "10.3390/cells11071193", "pmid": "35406757", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8997592"}, {"db": "pii", "key": "cells11071193"}], "notes": [], "created": "2023-02-16T08:24:58.046Z", "modified": "2023-02-16T08:24:58.149Z"}, {"entity": "publication", "iuid": "eca023eefa1847288514dbb81eadc725", "links": {"self": {"href": "https://publications.scilifelab.se/publication/eca023eefa1847288514dbb81eadc725.json"}, "display": {"href": "https://publications.scilifelab.se/publication/eca023eefa1847288514dbb81eadc725"}}, "title": "The Molecular Chaperone CCT Sequesters Gelsolin and Protects it from Cleavage by Caspase-3.", "authors": [{"family": "Cu\u00e9llar", "given": "Jorge", "initials": "J"}, {"family": "Vallin", "given": "Josefine", "initials": "J"}, {"family": "Svanstr\u00f6m", "given": "Andreas", "initials": "A"}, {"family": "Maestro-L\u00f3pez", "given": "Mois\u00e9s", "initials": "M"}, {"family": "Bueno-Carrasco", "given": "Mar\u00eda Teresa", "initials": "MT"}, {"family": "Ludlam", "given": "W Grant", "initials": "WG"}, {"family": "Willardson", "given": "Barry M", "initials": "BM"}, {"family": "Valpuesta", "given": "Jos\u00e9 M", "initials": "JM"}, {"family": "Grantham", "given": "Julie", "initials": "J"}], "type": "journal article", "published": "2022-03-15", "journal": {"title": "J. Mol. Biol.", "issn": "1089-8638", "volume": "434", "issue": "5", "pages": "167399", "issn-l": "0022-2836"}, "abstract": "The actin filament severing and capping protein gelsolin plays an important role in modulation of actin filament dynamics by influencing the number of actin filament ends. During apoptosis, gelsolin becomes constitutively active due to cleavage by caspase-3. In non-apoptotic cells gelsolin is activated by the binding of Ca2+. This activated form of gelsolin binds to, but is not a folding substrate of the molecular chaperone CCT/TRiC. Here we demonstrate that in vitro, gelsolin is protected from cleavage by caspase-3 in the presence of CCT. Cryoelectron microscopy and single particle 3D reconstruction of the CCT:gelsolin complex reveals that gelsolin is located in the interior of the chaperonin cavity, with a placement distinct from that of the obligate CCT folding substrates actin and tubulin. In cultured mouse melanoma B16F1 cells, gelsolin co-localises with CCT upon stimulation of actin dynamics at peripheral regions during lamellipodia formation. These data indicate that localised sequestration of gelsolin by CCT may provide spatial control of actin filament dynamics.", "doi": "10.1016/j.jmb.2021.167399", "pmid": "34896365", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S0022-2836(21)00636-7"}], "notes": [], "created": "2023-02-16T08:23:32.429Z", "modified": "2023-02-16T08:23:32.441Z"}, {"entity": "publication", "iuid": "e6083a339dec4dd7bf5e5f04089797d7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e6083a339dec4dd7bf5e5f04089797d7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e6083a339dec4dd7bf5e5f04089797d7"}}, "title": "NanoSIMS Imaging Reveals the Impact of Ligand-ASO Conjugate Stability on ASO Subcellular Distribution.", "authors": [{"family": "Kay", "given": "Emma", "initials": "E", "orcid": "0000-0001-9668-6753", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ff189b997464665bc014252804d7795.json"}}, {"family": "Stulz", "given": "Rouven", "initials": "R"}, {"family": "Becquart", "given": "C\u00e9cile", "initials": "C", "orcid": "0000-0002-7968-7129", "researcher": {"href": "https://publications.scilifelab.se/researcher/53c4dff8c3154c6884112040dd0469a0.json"}}, {"family": "Lovric", "given": "Jelena", "initials": "J"}, {"family": "T\u00e4ngemo", "given": "Carolina", "initials": "C"}, {"family": "Thomen", "given": "Aur\u00e9lien", "initials": "A"}, {"family": "Ba\u017edarevi\u0107", "given": "D\u017eenita", "initials": "D"}, {"family": "Najafinobar", "given": "Neda", "initials": "N"}, {"family": "Dahl\u00e9n", "given": "Anders", "initials": "A"}, {"family": "Pielach", "given": "Anna", "initials": "A"}, {"family": "Fernandez-Rodriguez", "given": "Julia", "initials": "J", "orcid": "0000-0003-4522-0966", "researcher": {"href": "https://publications.scilifelab.se/researcher/3bd9c743e99d479cb752aeec947acab3.json"}}, {"family": "Str\u00f6mberg", "given": "Roger", "initials": "R", "orcid": "0000-0002-7902-2688", "researcher": {"href": "https://publications.scilifelab.se/researcher/b76bd49836bf4c3eb0cfeac29ed6a238.json"}}, {"family": "\u00c4mm\u00e4l\u00e4", "given": "Carina", "initials": "C"}, {"family": "Andersson", "given": "Shalini", "initials": "S", "orcid": "0000-0002-7051-2189", "researcher": {"href": "https://publications.scilifelab.se/researcher/4bec6d49d3824027a9f1add9fc09588d.json"}}, {"family": "Kurczy", "given": "Michael", "initials": "M"}], "type": "journal article", "published": "2022-02-21", "journal": {"title": "Pharmaceutics", "issn": "1999-4923", "volume": "14", "issue": "2", "pages": "463", "issn-l": null}, "abstract": "The delivery of antisense oligonucleotides (ASOs) to specific cell types via targeted endocytosis is challenging due to the low cell surface expression of target receptors and inefficient escape of ASOs from the endosomal pathway. Conjugating ASOs to glucagon-like peptide 1 (GLP1) leads to efficient target knockdown, specifically in pancreatic \u03b2-cells. It is presumed that ASOs dissociate from GLP1 intracellularly to enable an ASO interaction with its target RNA. It is unknown where or when this happens following GLP1-ASO binding to GLP1R and endocytosis. Here, we use correlative nanoscale secondary ion mass spectroscopy (NanoSIMS) and transmission electron microscopy to explore GLP1-ASO subcellular trafficking in GLP1R overexpressing HEK293 cells. We isotopically label both eGLP1 and ASO, which do not affect the eGLP1-ASO conjugate function. We found that the eGLP1 peptide and ASO are not detected at the same level in the same endosomes, within 30 min of GLP1R-HEK293 cell exposure to eGLP1-ASO. When we utilized different linker chemistry to stabilize the GLP1-ASO conjugate, we observed more ASO located with GLP1 compared to cell incubation with the less stable conjugate. Overall, our work suggests that the ASO separates from GLP1 relatively early in the endocytic pathway, and that linker chemistry might impact the GLP1-ASO function.", "doi": "10.3390/pharmaceutics14020463", "pmid": "35214195", "labels": {"Integrated Microscopy Technologies Gothenburg": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC8876276"}, {"db": "pii", "key": "pharmaceutics14020463"}], "notes": [], "created": "2023-02-16T08:24:22.943Z", "modified": "2023-12-01T10:57:23.359Z"}, {"entity": "publication", "iuid": "4d938430321a45eea09d9bb81bc35a1c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4d938430321a45eea09d9bb81bc35a1c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4d938430321a45eea09d9bb81bc35a1c"}}, "title": "Structural amyloid plaque polymorphism is associated with distinct lipid accumulations revealed by trapped ion mobility mass spectrometry imaging.", "authors": [{"family": "Michno", "given": "Wojciech", "initials": "W", "orcid": "0000-0002-3096-3604", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b4307eb6e45426e8176337e88c9c344.json"}}, {"family": "Wehrli", "given": "Patrick M", "initials": "PM"}, {"family": "Koutarapu", "given": "Srinivas", "initials": "S"}, {"family": "Marsching", "given": "Christian", "initials": "C"}, {"family": "Minta", "given": "Karolina", "initials": "K"}, {"family": "Ge", "given": "Junyue", "initials": "J"}, {"family": "Meyer", "given": "Sven W", "initials": "SW"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H", "orcid": "0000-0003-3930-4354", "researcher": {"href": "https://publications.scilifelab.se/researcher/85efee74eb4a4b38b63cf2823d204529.json"}}, {"family": "Blennow", "given": "Kaj", "initials": "K"}, {"family": "Henkel", "given": "Corinna", "initials": "C"}, {"family": "Oetjen", "given": "Janina", "initials": "J", "orcid": "0000-0002-4088-5742", "researcher": {"href": "https://publications.scilifelab.se/researcher/aa10e19731a847d1a6810778bcdee4fe.json"}}, {"family": "Hopf", "given": "Carsten", "initials": "C", "orcid": "0000-0003-0802-6451", "researcher": {"href": "https://publications.scilifelab.se/researcher/178878399aac4cd6bf793f3720c75365.json"}}, {"family": "Hanrieder", "given": "J\u00f6rg", "initials": "J", "orcid": "0000-0001-6059-198X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e65454100674f98bf8f2575093f2441.json"}}], "type": "journal article", "published": "2022-02-00", "journal": {"title": "J. Neurochem.", "issn": "1471-4159", "volume": "160", "issue": "4", "pages": "482-498", "issn-l": "0022-3042"}, "abstract": "Understanding of Alzheimer's disease (AD) pathophysiology requires molecular assessment of how key pathological factors, specifically amyloid \u03b2 (A\u03b2) plaques, influence the surrounding microenvironment. Here, neuronal lipids have been implicated in A\u03b2 plaque pathology, though the lipid microenvironment in direct proximity to A\u03b2 plaques is still not fully resolved. A further challenge is the microenvironmental molecular heterogeneity, across structurally polymorphic A\u03b2 features, such as diffuse, immature, and mature, fibrillary aggregates, whose resolution requires the integration of advanced, multimodal chemical imaging tools. Herein, we used matrix-assisted laser desorption/ionization trapped ion mobility spectrometry time-of-flight based mass spectrometry imaging (MALDI TIMS TOF MSI) in combination with hyperspectral confocal microscopy to probe the lipidomic microenvironment associated with structural polymorphism of A\u03b2 plaques in transgenic Alzheimer's disease mice (tgAPPSWE ). Using on tissue and ex situ validation, TIMS MS/MS facilitated unambiguous identification of isobaric lipid species that showed plaque pathology-associated localizations. Integrated multivariate imaging data analysis revealed multiple, A\u03b2 plaque-enriched lipid patterns for gangliosides (GM), phosphoinositols (PI), phosphoethanolamines (PE), and phosphatidic acids (PA). Conversely, sulfatides (ST), cardiolipins (CL), and polyunsaturated fatty acid (PUFA)-conjugated phosphoserines (PS), and PE were depleted at plaques. Hyperspectral amyloid imaging further delineated the unique distribution of PA and PE species to mature plaque core regions, while PI, LPI, GM2 and GM3 lipids localized to immature A\u03b2 aggregates present within the periphery of A\u03b2 plaques. Finally, we followed AD pathology-associated lipid changes over time, identifying plaque- growth and maturation to be characterized by peripheral accumulation of PI (18:0/22:6). Together, these data demonstrate the potential of multimodal imaging approaches to overcome limitations associated with conventional advanced MS imaging applications. This allowed for the differentiation of both distinct lipid components in a complex micro-environment as well as their correlation to disease-relevant amyloid plaque polymorphs. Cover Image for this issue: https://doi.org/10.1111/jnc.15390.", "doi": "10.1111/jnc.15557", "pmid": "34882796", "labels": {"Integrated Microscopy Technologies Gothenburg": "Collaborative"}, "xrefs": [], "notes": [], "created": "2023-02-16T08:24:46.768Z", "modified": "2023-02-16T08:24:46.828Z"}, {"entity": "publication", "iuid": "2a7d9ea2d442431f9aa88726812f7000", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2a7d9ea2d442431f9aa88726812f7000.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2a7d9ea2d442431f9aa88726812f7000"}}, "title": "Reactive astrocytes prevent maladaptive plasticity after ischemic stroke.", "authors": [{"family": "Aswendt", "given": "Markus", "initials": "M"}, {"family": "Wilhelmsson", "given": "Ulrika", "initials": "U"}, {"family": "Wieters", "given": "Frederique", "initials": "F"}, {"family": "Stokowska", "given": "Anna", "initials": "A"}, {"family": "Schmitt", "given": "Felix Johannes", "initials": "FJ"}, {"family": "Pallast", "given": "Niklas", "initials": "N"}, {"family": "de Pablo", "given": "Yolanda", "initials": "Y"}, {"family": "Mohammed", "given": "Lava", "initials": "L"}, {"family": "Hoehn", "given": "Mathias", "initials": "M"}, {"family": "Pekna", "given": "Marcela", "initials": "M"}, {"family": "Pekny", "given": "Milos", "initials": "M"}], "type": "journal article", "published": "2022-02-00", "journal": {"title": "Prog Neurobiol", "issn": "1873-5118", "volume": "209", "pages": "102199", "issn-l": null}, "abstract": "Restoration of functional connectivity is a major contributor to functional recovery after stroke. We investigated the role of reactive astrocytes in functional connectivity and recovery after photothrombotic stroke in mice with attenuated reactive gliosis (GFAP-/-Vim-/-). Infarct volume and longitudinal functional connectivity changes were determined by in vivo T2-weighted magnetic resonance imaging (MRI) and resting-state functional MRI. Sensorimotor function was assessed with behavioral tests, and glial and neural plasticity responses were quantified in the peri-infarct region. Four weeks after stroke, GFAP-/-Vim-/- mice showed impaired recovery of sensorimotor function and aberrant restoration of global neuronal connectivity. These mice also exhibited maladaptive plasticity responses, shown by higher number of lost and newly formed functional connections between primary and secondary targets of cortical stroke regions and increased peri-infarct expression of the axonal plasticity marker Gap43. We conclude that reactive astrocytes modulate recovery-promoting plasticity responses after ischemic stroke.", "doi": "10.1016/j.pneurobio.2021.102199", "pmid": "34921928", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S0301-0082(21)00213-6"}], "notes": [], "created": "2023-02-16T08:23:25.348Z", "modified": "2023-02-16T08:23:25.350Z"}, {"entity": "publication", "iuid": "3d784932a3d947f999ea5ca837c358d2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3d784932a3d947f999ea5ca837c358d2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3d784932a3d947f999ea5ca837c358d2"}}, "title": "Proteomic characterisation of polyglucosan bodies in skeletal muscle in RBCK1 deficiency.", "authors": [{"family": "Thomsen", "given": "Christer", "initials": "C", "orcid": "0000-0001-5416-552X", "researcher": {"href": "https://publications.scilifelab.se/researcher/2ba5b39b720d44e386085fc0e67be556.json"}}, {"family": "Malfatti", "given": "Edoardo", "initials": "E"}, {"family": "Jovanovic", "given": "Ana", "initials": "A"}, {"family": "Roberts", "given": "Mark", "initials": "M"}, {"family": "Kalev", "given": "Ognian", "initials": "O"}, {"family": "Lindberg", "given": "Christopher", "initials": "C"}, {"family": "Oldfors", "given": "Anders", "initials": "A", "orcid": "0000-0002-5758-7397", "researcher": {"href": "https://publications.scilifelab.se/researcher/e82034663f6647cd9827871bfca633ef.json"}}], "type": "journal article", "published": "2022-02-00", "journal": {"title": "Neuropathol Appl Neurobiol", "issn": "1365-2990", "volume": "48", "issue": "1", "pages": "e12761", "issn-l": null}, "abstract": "Several neurodegenerative and neuromuscular disorders are characterised by storage of polyglucosan, consisting of proteins and amylopectin-like polysaccharides, which are less branched than in normal glycogen. Such diseases include Lafora disease, branching enzyme deficiency, glycogenin-1 deficiency, polyglucosan body myopathy type 1 (PGBM1) due to RBCK1 deficiency and others. The protein composition of polyglucosan bodies is largely unknown.\n\nWe combined quantitative mass spectrometry, immunohistochemical and western blot analyses to identify the principal protein components of polyglucosan bodies in PGBM1. Histologically stained tissue sections of skeletal muscle from four patients were used to isolate polyglucosan deposits and control regions by laser microdissection. Prior to mass spectrometry, samples were labelled with tandem mass tags that enable quantitative comparison and multiplexed analysis of dissected samples. To study the distribution and expression of the accumulated proteins, immunohistochemical and western blot analyses were performed.\n\nAccumulated proteins were mainly components of glycogen metabolism and protein quality control pathways. The majority of fibres showed depletion of glycogen and redistribution of key enzymes of glycogen metabolism to the polyglucosan bodies. The polyglucosan bodies also showed accumulation of proteins involved in the ubiquitin-proteasome and autophagocytosis systems and protein chaperones.\n\nThe sequestration of key enzymes of glycogen metabolism to the polyglucosan bodies may explain the glycogen depletion in the fibres and muscle function impairment. The accumulation of components of the protein quality control systems and other proteins frequently found in protein aggregate disorders indicates that protein aggregation may be an essential part of the pathobiology of polyglucosan storage.", "doi": "10.1111/nan.12761", "pmid": "34405429", "labels": {"Clinical Genomics Gothenburg": "Service", "Integrated Microscopy Technologies Gothenburg": "Service", "Glycoproteomics and MS Proteomics": "Service", "Clinical Genomics": "Service"}, "xrefs": [], "notes": [], "created": "2022-12-02T12:22:17.396Z", "modified": "2024-01-16T13:46:29.630Z"}, {"entity": "publication", "iuid": "3a2ea3833cf745f0a0fceb4c0573a25e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3a2ea3833cf745f0a0fceb4c0573a25e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3a2ea3833cf745f0a0fceb4c0573a25e"}}, "title": "Characterization of surface markers on extracellular vesicles isolated from lymphatic exudate from patients with breast cancer.", "authors": [{"family": "Ekstr\u00f6m", "given": "Karin", "initials": "K"}, {"family": "Crescitelli", "given": "Rossella", "initials": "R"}, {"family": "P\u00e9tursson", "given": "Hafsteinn Ingi", "initials": "HI"}, {"family": "Johansson", "given": "Junko", "initials": "J"}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C"}, {"family": "Olofsson Bagge", "given": "Roger", "initials": "R"}], "type": "journal article", "published": "2022-01-10", "journal": {"title": "BMC Cancer", "issn": "1471-2407", "volume": "22", "issue": "1", "pages": "50", "issn-l": "1471-2407"}, "abstract": "Breast cancer is the most common cancer, and the leading cause of cancer-related deaths, among females world-wide. Recent research suggests that extracellular vesicles (EVs) play a major role in the development of breast cancer metastasis. Axillary lymph node dissection (ALND) is a procedure in patients with known lymph node metastases, and after surgery large amounts of serous fluid are produced from the axilla. The overall aim was to isolate and characterize EVs from axillary serous fluid, and more specifically to determine if potential breast cancer biomarkers could be identified.\n\nLymphatic drain fluid was collected from 7 patients with breast cancer the day after ALND. EVs were isolated using size exclusion chromatography, quantified and detected by nanoparticle tracking analysis, electron microscopy, nano flow cytometry and western blot. The expression of 37 EV surface proteins was evaluated by flow cytometry using the MACSPlex Exosome kit.\n\nLymphatic drainage exudate retrieved after surgery from all 7 patients contained EVs. The isolated EVs were positive for the typical EV markers CD9, CD63, CD81 and Flotillin-1 while albumin was absent, indicating low contamination from blood proteins. In total, 24 different EV surface proteins were detected. Eleven of those proteins were detected in all patients, including the common EV markers CD9, CD63 and CD81, cancer-related markers CD24, CD29, CD44 and CD146, platelet markers CD41b, CD42a and CD62p as well as HLA-DR/DP/DQ. Furthermore, CD29 and CD146 were enriched in Her2+ patients compared to patients with Her2- tumors.\n\nLymphatic drainage exudate retrieved from breast cancer patients after surgery contains EVs that can be isolated using SEC isolation. The EVs have several cancer-related markers including CD24, CD29, CD44 and CD146, proteins of potential interest as biomarkers as well as to increase the understanding of the mechanisms of cancer biology.", "doi": "10.1186/s12885-021-08870-w", "pmid": "35012489", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8744234"}, {"db": "pii", "key": "10.1186/s12885-021-08870-w"}], "notes": [], "created": "2023-02-16T08:23:50.786Z", "modified": "2023-02-16T08:23:50.789Z"}, {"entity": "publication", "iuid": "05ea7c8e845547fa864be61107db26eb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/05ea7c8e845547fa864be61107db26eb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/05ea7c8e845547fa864be61107db26eb"}}, "title": "TRAPing Ghrelin-Activated Circuits: A Novel Tool to Identify, Target and Control Hormone-Responsive Populations in TRAP2 Mice.", "authors": [{"family": "Stoltenborg", "given": "Iris", "initials": "I"}, {"family": "Peris-Sampedro", "given": "Fiona", "initials": "F"}, {"family": "Sch\u00e9le", "given": "Erik", "initials": "E"}, {"family": "Le May", "given": "Marie V", "initials": "MV"}, {"family": "Adan", "given": "Roger A H", "initials": "RAH"}, {"family": "Dickson", "given": "Suzanne L", "initials": "SL", "orcid": "0000-0002-3822-5294", "researcher": {"href": "https://publications.scilifelab.se/researcher/eabf6c037c6640cf95d64eebfb3f62e9.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": "The availability of Cre-based mouse lines for visualizing and targeting populations of hormone-sensitive cells has helped identify the neural circuitry driving hormone effects. However, these mice have limitations and may not even be available. For instance, the development of the first ghrelin receptor (Ghsr)-IRES-Cre model paved the way for using the Cre-lox system to identify and selectively manipulate ghrelin-responsive populations. The insertion of the IRES-Cre cassette, however, interfered with Ghsr expression, resulting in defective GHSR signaling and a pronounced phenotype in the homozygotes. As an alternative strategy to target ghrelin-responsive cells, we hereby utilize TRAP2 (targeted recombination in active populations) mice in which it is possible to gain genetic access to ghrelin-activated populations. In TRAP2 mice crossed with a reporter strain, we visualized ghrelin-activated cells and found, as expected, much activation in the arcuate nucleus (Arc). We then stimulated this population using a chemogenetic approach and found that this was sufficient to induce an orexigenic response of similar magnitude to that induced by peripheral ghrelin injection. The stimulation of this population also impacted food choice. Thus, the TRAPing of hormone-activated neurons (here exemplified by ghrelin-activated pathways) provides a complimentary/alternative technique to visualize, access and control discrete pathways, linking hormone action to circuit function.", "doi": "10.3390/ijms23010559", "pmid": "35008985", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8745172"}, {"db": "pii", "key": "ijms23010559"}], "notes": [], "created": "2023-02-16T08:25:22.182Z", "modified": "2023-02-16T08:25:22.224Z"}, {"entity": "publication", "iuid": "6f7e778f15c145b0af5aa10a4539708e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6f7e778f15c145b0af5aa10a4539708e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6f7e778f15c145b0af5aa10a4539708e"}}, "title": "Localization and Absolute Quantification of Dopamine in Discrete Intravesicular Compartments Using NanoSIMS Imaging.", "authors": [{"family": "Rabasco", "given": "Stefania", "initials": "S", "orcid": "0000-0001-5260-2909", "researcher": {"href": "https://publications.scilifelab.se/researcher/415d580e988f436ca6b5f3ba56ca5f9f.json"}}, {"family": "Nguyen", "given": "Tho D K", "initials": "TDK", "orcid": "0000-0002-8306-6181", "researcher": {"href": "https://publications.scilifelab.se/researcher/b610c31c3e7d421a9e7059f91400576c.json"}}, {"family": "Gu", "given": "Chaoyi", "initials": "C"}, {"family": "Kurczy", "given": "Michael E", "initials": "ME"}, {"family": "Phan", "given": "Nhu T N", "initials": "NTN"}, {"family": "Ewing", "given": "Andrew G", "initials": "AG", "orcid": "0000-0002-2084-0133", "researcher": {"href": "https://publications.scilifelab.se/researcher/c6ecb82dc7a6423fa0876822f5568e1b.json"}}], "type": "journal article", "published": "2021-12-23", "journal": {"title": "Int J Mol Sci", "issn": "1422-0067", "volume": "23", "issue": "1", "issn-l": null}, "abstract": "The absolute concentration and the compartmentalization of analytes in cells and organelles are crucial parameters in the development of drugs and drug delivery systems, as well as in the fundamental understanding of many cellular processes. Nanoscale secondary ion mass spectrometry (NanoSIMS) imaging is a powerful technique which allows subcellular localization of chemical species with high spatial and mass resolution, and high sensitivity. In this study, we combined NanoSIMS imaging with spatial oversampling with transmission electron microscopy (TEM) imaging to discern the compartments (dense core and halo) of large dense core vesicles in a model cell line used to study exocytosis, and to localize 13C dopamine enrichment following 4-6 h of 150 \u03bcM 13C L-3,4-dihydroxyphenylalanine (L-DOPA) incubation. In addition, the absolute concentrations of 13C dopamine in distinct vesicle domains as well as in entire single vesicles were quantified and validated by comparison to electrochemical data. We found concentrations of 87.5 mM, 16.0 mM and 39.5 mM for the dense core, halo and the whole vesicle, respectively. This approach adds to the potential of using combined TEM and NanoSIMS imaging to perform absolute quantification and directly measure the individual contents of nanometer-scale organelles.", "doi": "10.3390/ijms23010160", "pmid": "35008583", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8745556"}, {"db": "pii", "key": "ijms23010160"}], "notes": [], "created": "2023-02-16T08:21:49.084Z", "modified": "2023-02-16T08:21:49.190Z"}, {"entity": "publication", "iuid": "052e2a70a1e94719a6169ea6f41fec51", "links": {"self": {"href": "https://publications.scilifelab.se/publication/052e2a70a1e94719a6169ea6f41fec51.json"}, "display": {"href": "https://publications.scilifelab.se/publication/052e2a70a1e94719a6169ea6f41fec51"}}, "title": "C3a Receptor Signaling Inhibits Neurodegeneration Induced by Neonatal Hypoxic-Ischemic Brain Injury.", "authors": [{"family": "Pozo-Rodrig\u00e1lvarez", "given": "Andrea", "initials": "A"}, {"family": "Li", "given": "YiXian", "initials": "Y"}, {"family": "Stokowska", "given": "Anna", "initials": "A"}, {"family": "Wu", "given": "Jingyun", "initials": "J"}, {"family": "Dehm", "given": "Verena", "initials": "V"}, {"family": "Sourkova", "given": "Hana", "initials": "H"}, {"family": "Steinbusch", "given": "Harry", "initials": "H"}, {"family": "Mallard", "given": "Carina", "initials": "C"}, {"family": "Hagberg", "given": "Henrik", "initials": "H"}, {"family": "Pekny", "given": "Milos", "initials": "M"}, {"family": "Pekna", "given": "Marcela", "initials": "M"}], "type": "journal article", "published": "2021-12-17", "journal": {"title": "Front Immunol", "issn": "1664-3224", "volume": "12", "pages": "768198", "issn-l": "1664-3224"}, "abstract": "Hypoxic-ischemic neonatal encephalopathy due to perinatal asphyxia is the leading cause of brain injury in newborns. Clinical data suggest that brain inflammation induced by perinatal insults can persist for years. We previously showed that signaling through the receptor for complement peptide C3a (C3aR) protects against cognitive impairment induced by experimental perinatal asphyxia. To investigate the long-term neuropathological effects of hypoxic-ischemic injury to the developing brain and the role of C3aR signaling therein, we subjected wildtype mice, C3aR deficient mice, and mice expressing biologically active C3a in the CNS to mild hypoxic-ischemic brain injury on postnatal day 9. We found that such injury triggers neurodegeneration and pronounced reactive gliosis in the ipsilesional hippocampus both of which persist long into adulthood. Transgenic expression of C3a in reactive astrocytes reduced hippocampal neurodegeneration and reactive gliosis. In contrast, neurodegeneration and microglial cell density increased in mice lacking C3aR. Intranasal administration of C3a for 3 days starting 1 h after induction of hypoxia-ischemia reduced neurodegeneration and reactive gliosis in the hippocampus of wildtype mice. We conclude that neonatal hypoxic-ischemic brain injury leads to long-lasting neurodegeneration. This neurodegeneration is substantially reduced by treatment with C3aR agonists, conceivably through modulation of reactive gliosis.", "doi": "10.3389/fimmu.2021.768198", "pmid": "34975856", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8718687"}], "notes": [], "created": "2023-02-16T08:21:44.001Z", "modified": "2023-02-16T08:21:44.014Z"}, {"entity": "publication", "iuid": "5a5df4b4f8e949bda0e039f8e55481c0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5a5df4b4f8e949bda0e039f8e55481c0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5a5df4b4f8e949bda0e039f8e55481c0"}}, "title": "Identification of Novel Neurocircuitry Through Which Leptin Targets Multiple Inputs to the Dopamine System to Reduce Food Reward Seeking.", "authors": [{"family": "Omrani", "given": "Azar", "initials": "A"}, {"family": "de Vrind", "given": "Veronne A J", "initials": "VAJ"}, {"family": "Lodder", "given": "Bart", "initials": "B"}, {"family": "Stoltenborg", "given": "Iris", "initials": "I"}, {"family": "Kooij", "given": "Karlijn", "initials": "K"}, {"family": "Wolterink-Donselaar", "given": "Inge G", "initials": "IG"}, {"family": "Luijendijk-Berg", "given": "Mieneke C M", "initials": "MCM"}, {"family": "Garner", "given": "Keith M", "initials": "KM"}, {"family": "Van't Sant", "given": "Lisanne J", "initials": "LJ"}, {"family": "Rozeboom", "given": "Annemieke", "initials": "A"}, {"family": "Dickson", "given": "Suzanne L", "initials": "SL"}, {"family": "Meye", "given": "Frank J", "initials": "FJ"}, {"family": "Adan", "given": "Roger A H", "initials": "RAH"}], "type": "journal article", "published": "2021-12-15", "journal": {"title": "Biol. Psychiatry", "issn": "1873-2402", "volume": "90", "issue": "12", "pages": "843-852", "issn-l": "0006-3223"}, "abstract": "Leptin reduces the motivation to obtain food by modulating activity of the mesolimbic dopamine (DA) system upon presentation of cues that predict a food reward. Although leptin directly reduces the activity of ventral tegmental area (VTA) DA neurons, the majority of leptin receptor (LepR)-expressing DA neurons do not project to the nucleus accumbens, the projection implicated in driving food reward seeking. Therefore, the precise locus of leptin action to modulate motivation for a food reward is unresolved.\n\nWe used transgenic mice expressing Cre recombinase under the control of the LepR promoter, anatomical tracing, optogenetics-assisted patch-clamp electrophysiology, in vivo optogenetics with fiber photometric calcium measurements, and chemogenetics to unravel how leptin-targeted neurocircuitry inhibits food reward seeking.\n\nA large number of DA neurons projecting to the nucleus accumbens are innervated by local VTA LepR-expressing GABA (gamma-aminobutyric acid) neurons. Leptin enhances the activity of these GABA neurons and thereby inhibits nucleus accumbens-projecting DA neurons. In addition, we find that lateral hypothalamic LepR-expressing neurons projecting to the VTA are inhibited by leptin and that these neurons modulate DA neurons indirectly via inhibition of VTA GABA neurons. In accordance with such a disinhibitory function, optogenetically stimulating lateral hypothalamic LepR projections to the VTA potently activates DA neurons in vivo. Moreover, we found that chemogenetic activation of lateral hypothalamic LepR neurons increases the motivation to obtain a food reward only when mice are in a positive energy balance.\n\nWe identify neurocircuitry through which leptin targets multiple inputs to the DA system to reduce food reward seeking.", "doi": "10.1016/j.biopsych.2021.02.017", "pmid": "33867112", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S0006-3223(21)00121-9"}], "notes": [], "created": "2023-02-16T08:21:02.144Z", "modified": "2023-02-16T08:21:02.148Z"}, {"entity": "publication", "iuid": "09b8ed2f417348cda619ef58869257db", "links": {"self": {"href": "https://publications.scilifelab.se/publication/09b8ed2f417348cda619ef58869257db.json"}, "display": {"href": "https://publications.scilifelab.se/publication/09b8ed2f417348cda619ef58869257db"}}, "title": "QUAREP-LiMi: a community endeavor to advance quality assessment and reproducibility in light microscopy.", "authors": [{"family": "Boehm", "given": "Ulrike", "initials": "U", "orcid": "0000-0001-7471-2244", "researcher": {"href": "https://publications.scilifelab.se/researcher/4c8a69a74a1d4760a424493c109ca0c1.json"}}, {"family": "Nelson", "given": "Glyn", "initials": "G", "orcid": "0000-0002-1895-4772", "researcher": {"href": "https://publications.scilifelab.se/researcher/e100d899ae034300b2b02acb18e7230e.json"}}, {"family": "Brown", "given": "Claire M", "initials": "CM", "orcid": "0000-0003-1622-663X", "researcher": {"href": "https://publications.scilifelab.se/researcher/24eba097d4c640c1a8b5ed14cbf2bec2.json"}}, {"family": "Bagley", "given": "Steve", "initials": "S", "orcid": "0000-0002-9007-7292", "researcher": {"href": "https://publications.scilifelab.se/researcher/9dbacecc35284915b9cbedde090f9e41.json"}}, {"family": "Bajcsy", "given": "Peter", "initials": "P"}, {"family": "Bischof", "given": "Johanna", "initials": "J"}, {"family": "Dauphin", "given": "Aurelien", "initials": "A", "orcid": "0000-0001-9744-8458", "researcher": {"href": "https://publications.scilifelab.se/researcher/6e1d436989d14fff9de0d21ea33a88fd.json"}}, {"family": "Dobbie", "given": "Ian M", "initials": "IM", "orcid": "0000-0002-5531-5865", "researcher": {"href": "https://publications.scilifelab.se/researcher/8dc99f039409478dae6109879f91e3b5.json"}}, {"family": "Eriksson", "given": "John E", "initials": "JE"}, {"family": "Faklaris", "given": "Orestis", "initials": "O", "orcid": "0000-0001-5965-5405", "researcher": {"href": "https://publications.scilifelab.se/researcher/2857720b036a4963a37d94ac15c6abe0.json"}}, {"family": "Fernandez-Rodriguez", "given": "Julia", "initials": "J", "orcid": "0000-0003-4522-0966", "researcher": {"href": "https://publications.scilifelab.se/researcher/3bd9c743e99d479cb752aeec947acab3.json"}}, {"family": "Ferrand", "given": "Alexia", "initials": "A", "orcid": "0000-0001-7292-1325", "researcher": {"href": "https://publications.scilifelab.se/researcher/455de82cfa5a4d9aba1b38c7cd50e76c.json"}}, {"family": "Gelman", "given": "Laurent", "initials": "L"}, {"family": "Gheisari", "given": "Ali", "initials": "A", "orcid": "0000-0002-5344-5973", "researcher": {"href": "https://publications.scilifelab.se/researcher/2c9fdc637a4a4b5b8740b7366334b3ac.json"}}, {"family": "Hartmann", "given": "Hella", "initials": "H"}, {"family": "Kukat", "given": "Christian", "initials": "C", "orcid": "0000-0003-1508-0229", "researcher": {"href": "https://publications.scilifelab.se/researcher/30318e124470424395ae5e2e5fba8b40.json"}}, {"family": "Laude", "given": "Alex", "initials": "A", "orcid": "0000-0002-3853-1187", "researcher": {"href": "https://publications.scilifelab.se/researcher/c12931926a4f4975a2ceac257f91b55a.json"}}, {"family": "Mitkovski", "given": "Miso", "initials": "M", "orcid": "0000-0001-9195-2434", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f8693ab82bb48cb8d8cefcc7a661215.json"}}, {"family": "Munck", "given": "Sebastian", "initials": "S", "orcid": "0000-0002-5182-5358", "researcher": {"href": "https://publications.scilifelab.se/researcher/496d0d689ddc4bb3a619e0e5ec4d72c8.json"}}, {"family": "North", "given": "Alison J", "initials": "AJ"}, {"family": "Rasse", "given": "Tobias M", "initials": "TM", "orcid": "0000-0003-4090-7662", "researcher": {"href": "https://publications.scilifelab.se/researcher/6b882f919d714e959d5c56c48cc4653c.json"}}, {"family": "Resch-Genger", "given": "Ute", "initials": "U", "orcid": "0000-0002-0944-1115", "researcher": {"href": "https://publications.scilifelab.se/researcher/8d0fb8d6155341828c3b88e075f40854.json"}}, {"family": "Schuetz", "given": "Lucas C", "initials": "LC", "orcid": "0000-0003-2514-226X", "researcher": {"href": "https://publications.scilifelab.se/researcher/339c3d9ff13e43e08ebeab2432d4408f.json"}}, {"family": "Seitz", "given": "Arne", "initials": "A", "orcid": "0000-0002-5013-1557", "researcher": {"href": "https://publications.scilifelab.se/researcher/a22f2f49c174438a9c42e69ac6a451e8.json"}}, {"family": "Strambio-De-Castillia", "given": "Caterina", "initials": "C", "orcid": "0000-0002-1069-1816", "researcher": {"href": "https://publications.scilifelab.se/researcher/d56f91373ceb40bab6bae2635961bdf5.json"}}, {"family": "Swedlow", "given": "Jason R", "initials": "JR"}, {"family": "Nitschke", "given": "Roland", "initials": "R", "orcid": "0000-0002-9397-8475", "researcher": {"href": "https://publications.scilifelab.se/researcher/898e19916e4a4837a86226d735ff1ed8.json"}}], "type": "journal article", "published": "2021-12-00", "journal": {"title": "Nat. Methods", "issn": "1548-7105", "volume": "18", "issue": "12", "pages": "1423-1426", "issn-l": "1548-7091"}, "abstract": "The community-driven initiative \u2018ality Qussessment and Aroducibility for Instruments & Images in Repght Licroscopy\u2019 (QUAREP-LiMi) wants to improve reproducibility for light microscopy image data through quality control (QC) management of instruments and images. It aims for a common set of QC guidelines for hardware calibration, image acquisition, management and analysis.Mi", "doi": "10.1038/s41592-021-01162-y", "pmid": "34021279", "labels": {"Integrated Microscopy Technologies Gothenburg": "Collaborative"}, "xrefs": [{"db": "mid", "key": "NIHMS1833228"}, {"db": "pmc", "key": "PMC9443067"}, {"db": "pii", "key": "10.1038/s41592-021-01162-y"}], "notes": [], "created": "2023-12-01T10:56:59.095Z", "modified": "2023-12-01T10:56:59.671Z"}, {"entity": "publication", "iuid": "46533631c4d646e590c2e04ec5cbdf0f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/46533631c4d646e590c2e04ec5cbdf0f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/46533631c4d646e590c2e04ec5cbdf0f"}}, "title": "In vitro evaluation of chemical decontamination of titanium discs.", "authors": [{"family": "Ichioka", "given": "Yuki", "initials": "Y"}, {"family": "Derks", "given": "Jan", "initials": "J"}, {"family": "Dahl\u00e9n", "given": "Gunnar", "initials": "G"}, {"family": "Berglundh", "given": "Tord", "initials": "T"}, {"family": "Larsson", "given": "Lena", "initials": "L"}], "type": "journal article", "published": "2021-11-23", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "11", "issue": "1", "pages": "22753", "issn-l": "2045-2322"}, "abstract": "Peri-implant diseases are caused by bacterial biofilm colonizing implant surfaces. Prevention and management of peri-implant mucositis and peri-implantitis rely on effective biofilm removal. This study aimed to evaluate biofilm removal and cytocompatibility following chemo-mechanical surface decontamination of biofilm-coated titanium discs. Biofilm-coated (Streptococcus gordonii) discs, with either non-modified (smooth) or modified (rough) surfaces, were instrumented using a sterile gauze soaked in one out of four solutions: saline (NaCl), alkaline electrized water (AEW), citric acid (CA) or N-acetyl-L-cysteine (NAC). Non-contaminated, untreated titanium discs served as controls (C). Residual deposits (bacteria and gauze fibers) and cytocompatibility for osteoblast-like cells were evaluated using SEM and immunofluorescence. Cytotoxicity was assessed using WST-8 assay and immunofluorescence. All protocols were equally effective in removing bacteria from smooth surfaces, while AEW and CA were found to be superior at rough surfaces. AEW and NAC were superior in promoting cytocompatibility over NaCl. NAC and CA had a strong cytotoxic effect on osteoblast-like and fibroblast cells. In conclusion, AEW may be beneficial in the decontamination of implant surfaces, effectively removing bacterial biofilm and restoring cytocompatibility.", "doi": "10.1038/s41598-021-02220-3", "pmid": "34815486", "labels": {"Integrated Microscopy Technologies Gothenburg": "Technology development"}, "xrefs": [{"db": "pmc", "key": "PMC8611041"}, {"db": "pii", "key": "10.1038/s41598-021-02220-3"}], "notes": [], "created": "2023-02-16T08:17:30.177Z", "modified": "2023-02-16T08:17:30.180Z"}, {"entity": "publication", "iuid": "a2af20150cf0486c83ec277f00b1a410", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a2af20150cf0486c83ec277f00b1a410.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a2af20150cf0486c83ec277f00b1a410"}}, "title": "Deorphanization of novel biogenic amine-gated ion channels identifies a new serotonin receptor for learning.", "authors": [{"family": "Morud", "given": "Julia", "initials": "J"}, {"family": "Hardege", "given": "Iris", "initials": "I"}, {"family": "Liu", "given": "He", "initials": "H"}, {"family": "Wu", "given": "Taihong", "initials": "T"}, {"family": "Choi", "given": "Myung-Kyu", "initials": "MK"}, {"family": "Basu", "given": "Swaraj", "initials": "S"}, {"family": "Zhang", "given": "Yun", "initials": "Y"}, {"family": "Schafer", "given": "William R", "initials": "WR"}], "type": "journal article", "published": "2021-10-11", "journal": {"title": "Curr. Biol.", "issn": "1879-0445", "volume": "31", "issue": "19", "pages": "4282-4292.e6", "issn-l": "0960-9822"}, "abstract": "Pentameric ligand-gated ion channels (LGICs) play conserved, critical roles in both excitatory and inhibitory synaptic transmission and can be activated by diverse neurochemical ligands. We have performed a characterization of orphan channels from the nematode C. elegans, identifying five new monoamine-gated LGICs with diverse functional properties and expression postsynaptic to aminergic neurons. These include polymodal anion channels activated by both dopamine and tyramine, which may mediate inhibitory transmission by both molecules in vivo. Intriguingly, we also find that a novel serotonin-gated cation channel, LGC-50, is essential for aversive olfactory learning of pathogenic bacteria, a process known to depend on serotonergic neurotransmission. Remarkably, the redistribution of LGC-50 to neuronal processes is modulated by olfactory conditioning, and lgc-50 point mutations that cause misregulation of receptor membrane expression interfere with olfactory learning. Thus, the intracellular trafficking and localization of these receptors at synapses may represent a molecular cornerstone of the learning mechanism.", "doi": "10.1016/j.cub.2021.07.036", "pmid": "34388373", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8536830"}, {"db": "pii", "key": "S0960-9822(21)00991-X"}], "notes": [], "created": "2023-02-16T08:20:06.462Z", "modified": "2023-02-16T08:20:06.475Z"}, {"entity": "publication", "iuid": "5bd96c5ba07a441284381c33d5ac429b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5bd96c5ba07a441284381c33d5ac429b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5bd96c5ba07a441284381c33d5ac429b"}}, "title": "The localization of amyloid precursor protein to ependymal cilia in vertebrates and its role in ciliogenesis and brain development in zebrafish.", "authors": [{"family": "Chebli", "given": "Jasmine", "initials": "J", "orcid": "0000-0003-0791-3198", "researcher": {"href": "https://publications.scilifelab.se/researcher/0b0dd51631ce4c3c89a98b9d6c7d3d35.json"}}, {"family": "Rahmati", "given": "Maryam", "initials": "M"}, {"family": "Lashley", "given": "Tammaryn", "initials": "T", "orcid": "0000-0001-7389-0348", "researcher": {"href": "https://publications.scilifelab.se/researcher/533fe74a716840b2a55fddf0452f2a23.json"}}, {"family": "Edeman", "given": "Brigitta", "initials": "B"}, {"family": "Oldfors", "given": "Anders", "initials": "A", "orcid": "0000-0002-5758-7397", "researcher": {"href": "https://publications.scilifelab.se/researcher/e82034663f6647cd9827871bfca633ef.json"}}, {"family": "Zetterberg", "given": "Henrik", "initials": "H", "orcid": "0000-0003-3930-4354", "researcher": {"href": "https://publications.scilifelab.se/researcher/85efee74eb4a4b38b63cf2823d204529.json"}}, {"family": "Abramsson", "given": "Alexandra", "initials": "A", "orcid": "0000-0002-4715-9225", "researcher": {"href": "https://publications.scilifelab.se/researcher/7abde12dab2e4d338bc6e55933f07531.json"}}], "type": "journal article", "published": "2021-09-27", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "11", "issue": "1", "pages": "19115", "issn-l": "2045-2322"}, "abstract": "Amyloid precursor protein (APP) is expressed in many tissues in human, mice and in zebrafish. In zebrafish, there are two orthologues, Appa and Appb. Interestingly, some cellular processes associated with APP overlap with cilia-mediated functions. Whereas the localization of APP to primary cilia of in vitro-cultured cells has been reported, we addressed the presence of APP in motile and in non-motile sensory cilia and its potential implication for ciliogenesis using zebrafish, mouse, and human samples. We report that Appa and Appb are expressed by ciliated cells and become localized at the membrane of cilia in the olfactory epithelium, otic vesicle and in the brain ventricles of zebrafish embryos. App in ependymal cilia persisted in adult zebrafish and was also detected in mouse and human brain. Finally, we found morphologically abnormal ependymal cilia and smaller brain ventricles in appa-/-appb-/- mutant zebrafish. Our findings demonstrate an evolutionary conserved localisation of APP to cilia and suggest a role of App in ciliogenesis and cilia-related functions.", "doi": "10.1038/s41598-021-98487-7", "pmid": "34580355", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8476544"}, {"db": "pii", "key": "10.1038/s41598-021-98487-7"}], "notes": [], "created": "2023-02-16T08:14:17.553Z", "modified": "2023-02-16T08:14:17.703Z"}, {"entity": "publication", "iuid": "fd8235168188476480adfde25a4f9a73", "links": {"self": {"href": "https://publications.scilifelab.se/publication/fd8235168188476480adfde25a4f9a73.json"}, "display": {"href": "https://publications.scilifelab.se/publication/fd8235168188476480adfde25a4f9a73"}}, "title": "Genetic deletion of the ghrelin receptor (GHSR) impairs growth and blunts endocrine response to fasting in Ghsr-IRES-Cre mice.", "authors": [{"family": "Peris-Sampedro", "given": "Fiona", "initials": "F"}, {"family": "Stoltenborg", "given": "Iris", "initials": "I"}, {"family": "Le May", "given": "Marie V", "initials": "MV"}, {"family": "Zigman", "given": "Jeffrey M", "initials": "JM"}, {"family": "Adan", "given": "Roger A H", "initials": "RAH"}, {"family": "Dickson", "given": "Suzanne L", "initials": "SL"}], "type": "journal article", "published": "2021-09-00", "journal": {"title": "Mol Metab", "issn": "2212-8778", "volume": "51", "pages": "101223", "issn-l": "2212-8778"}, "abstract": "The orexigenic hormone ghrelin exerts its physiological effects by binding to and activating the growth hormone secretagogue receptor (GHSR). The recent development of a Ghsr-IRES-Cre knock-in mouse line has enabled to genetically access GHSR-expressing neurons. Inserting a Cre construct using a knock-in strategy, even when following an upstream internal ribosome entry site (IRES) can, however, interfere with expression of a targeted gene, with consequences for the phenotype emerging. This study aimed to phenotype, both physically and metabolically, heterozygous and homozygous Ghsr-IRES-Cre mice, with a view to discovering the extent to which the ghrelin signalling system remains functional in these mice.\n\nWe assessed feeding and arcuate nucleus (Arc) Fos activation in wild-type, heterozygous and homozygous Ghsr-IRES-Cre mice in response to peripherally-administered ghrelin. We also characterised their developmental and growth phenotypes, as well as their metabolic responses upon an overnight fast.\n\nInsertion of the IRES-Cre cassette into the 3'-untranslated region of the Ghsr gene led to a gene-dosage GHSR depletion in the Arc. Whereas heterozygotes remained ghrelin-responsive and more closely resembled wild-types, ghrelin had reduced orexigenic efficacy and failed to induce Arc Fos expression in homozygous littermates. Homozygotes had a lower body weight accompanied by a shorter body length, less fat tissue content, altered bone parameters, and lower insulin-like growth factor-1 levels compared to wild-type and heterozygous littermates. Moreover, both heterozygous and homozygous Ghsr-IRES-Cre mice lacked the usual fasting-induced rise in growth hormone (GH) and displayed an exaggerated drop in blood glucose and insulin compared to wild-types. Unexpectedly, fasting acyl-ghrelin levels were allele-dependently increased.\n\nOur data suggest that (i) heterozygous but not homozygous Ghsr-IRES-Cre mice retain the usual responsiveness to administered ghrelin, (ii) the impact of fasting on GH release and glucose homeostasis is altered even when only one copy of the Ghsr gene is non-functional (as in heterozygous Ghsr-IRES-Cre mice) and (iii) homozygous Ghsr-IRES-Cre mice exhibit growth retardation. Of the many transgenic models of suppressed ghrelin signalling, Ghsr-IRES-Cre mice emerge as best representing the full breadth of the expected phenotype with respect to body weight, growth, and metabolic parameters.", "doi": "10.1016/j.molmet.2021.101223", "pmid": "33798772", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8102639"}, {"db": "pii", "key": "S2212-8778(21)00067-3"}], "notes": [], "created": "2023-02-16T08:21:34.201Z", "modified": "2023-02-16T08:21:34.215Z"}, {"entity": "publication", "iuid": "6c5dee338d06472182df2147770ff4cc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6c5dee338d06472182df2147770ff4cc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6c5dee338d06472182df2147770ff4cc"}}, "title": "A genetic titration of membrane composition in Caenorhabditis elegans reveals its importance for multiple cellular and physiological traits.", "authors": [{"family": "Devkota", "given": "Ranjan", "initials": "R"}, {"family": "Kaper", "given": "Delaney", "initials": "D"}, {"family": "Bodhicharla", "given": "Rakesh", "initials": "R"}, {"family": "Henricsson", "given": "Marcus", "initials": "M"}, {"family": "Bor\u00e9n", "given": "Jan", "initials": "J"}, {"family": "Pilon", "given": "Marc", "initials": "M", "orcid": "0000-0003-3919-2882", "researcher": {"href": "https://publications.scilifelab.se/researcher/d45c4ecf9afe463c971af2de53a770a8.json"}}], "type": "journal article", "published": "2021-08-26", "journal": {"title": "Genetics", "issn": "1943-2631", "volume": "219", "issue": "1", "issn-l": "0016-6731"}, "abstract": "Communicating editor: B. Grant The composition and biophysical properties of cellular membranes must be tightly regulated to maintain the proper functions of myriad processes within cells. To better understand the importance of membrane homeostasis, we assembled a panel of five Caenorhabditis elegans strains that show a wide span of membrane composition and properties, ranging from excessively rich in saturated fatty acids (SFAs) and rigid to excessively rich in polyunsaturated fatty acids (PUFAs) and fluid. The genotypes of the five strain are, from most rigid to most fluid: paqr-1(tm3262); paqr-2(tm3410), paqr-2(tm3410), N2 (wild-type), mdt-15(et14); nhr-49(et8), and mdt-15(et14); nhr-49(et8); acs-13(et54). We confirmed the excess SFA/rigidity-to-excess PUFA/fluidity gradient using the methods of fluorescence recovery after photobleaching (FRAP) and lipidomics analysis. The five strains were then studied for a variety of cellular and physiological traits and found to exhibit defects in: permeability, lipid peroxidation, growth at different temperatures, tolerance to SFA-rich diets, lifespan, brood size, vitellogenin trafficking, oogenesis, and autophagy during starvation. The excessively rigid strains often exhibited defects in opposite directions compared to the excessively fluid strains. We conclude that deviation from wild-type membrane homeostasis is pleiotropically deleterious for numerous cellular/physiological traits. The strains introduced here should prove useful to further study the cellular and physiological consequences of impaired membrane homeostasis.", "doi": "10.1093/genetics/iyab093", "pmid": "34125894", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC9335940"}, {"db": "pii", "key": "6298595"}], "notes": [], "created": "2023-02-16T08:15:40.909Z", "modified": "2023-02-16T08:15:40.926Z"}, {"entity": "publication", "iuid": "2fa2f808b1704aa48c255a9d72580b1f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2fa2f808b1704aa48c255a9d72580b1f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2fa2f808b1704aa48c255a9d72580b1f"}}, "title": "The mitochondrial single-stranded DNA binding protein is essential for initiation of mtDNA replication.", "authors": [{"family": "Jiang", "given": "Min", "initials": "M", "orcid": "0000-0002-7005-937X", "researcher": {"href": "https://publications.scilifelab.se/researcher/862b43b10af944108db18b48d57ba4a1.json"}}, {"family": "Xie", "given": "Xie", "initials": "X", "orcid": "0000-0002-8021-9875", "researcher": {"href": "https://publications.scilifelab.se/researcher/c0feb563228e42579c5aee512d250e5d.json"}}, {"family": "Zhu", "given": "Xuefeng", "initials": "X", "orcid": "0000-0002-4759-4446", "researcher": {"href": "https://publications.scilifelab.se/researcher/eebd5f32ac0c48869c90ba2d2ba94fa9.json"}}, {"family": "Jiang", "given": "Shan", "initials": "S", "orcid": "0000-0003-2020-6447", "researcher": {"href": "https://publications.scilifelab.se/researcher/6bd8b6e66470485f9978b3db1bb3b765.json"}}, {"family": "Milenkovic", "given": "Dusanka", "initials": "D", "orcid": "0000-0003-0151-8760", "researcher": {"href": "https://publications.scilifelab.se/researcher/7667a08efad244b88892a772f51ccf50.json"}}, {"family": "Misic", "given": "Jelena", "initials": "J", "orcid": "0000-0002-1562-0582", "researcher": {"href": "https://publications.scilifelab.se/researcher/ed5101973de04ee896ee41a2657612c4.json"}}, {"family": "Shi", "given": "Yonghong", "initials": "Y"}, {"family": "Tandukar", "given": "Nirwan", "initials": "N", "orcid": "0000-0001-7769-5304", "researcher": {"href": "https://publications.scilifelab.se/researcher/6fc8863a94e6450c9218b97453380785.json"}}, {"family": "Li", "given": "Xinping", "initials": "X", "orcid": "0000-0002-7427-0017", "researcher": {"href": "https://publications.scilifelab.se/researcher/836410d8d48f47fbb5bfd46deac8f6e8.json"}}, {"family": "Atanassov", "given": "Ilian", "initials": "I", "orcid": "0000-0001-8259-2545", "researcher": {"href": "https://publications.scilifelab.se/researcher/f8d22eab41e44364be8966abaf693de1.json"}}, {"family": "Jenninger", "given": "Louise", "initials": "L"}, {"family": "Hoberg", "given": "Emily", "initials": "E"}, {"family": "Albarran-Gutierrez", "given": "Sara", "initials": "S", "orcid": "0000-0003-1403-3922", "researcher": {"href": "https://publications.scilifelab.se/researcher/9231ff3b6f994dfaa9bc8f2a52746d78.json"}}, {"family": "Szilagyi", "given": "Zsolt", "initials": "Z"}, {"family": "Macao", "given": "Bertil", "initials": "B"}, {"family": "Siira", "given": "Stefan J", "initials": "SJ", "orcid": "0000-0002-8391-0143", "researcher": {"href": "https://publications.scilifelab.se/researcher/4739679420014daca252a8a6ea68597e.json"}}, {"family": "Carelli", "given": "Valerio", "initials": "V", "orcid": "0000-0003-4923-6404", "researcher": {"href": "https://publications.scilifelab.se/researcher/55d1ecff8faa4f4e90e515a6472f7701.json"}}, {"family": "Griffith", "given": "Jack D", "initials": "JD"}, {"family": "Gustafsson", "given": "Claes M", "initials": "CM"}, {"family": "Nicholls", "given": "Thomas J", "initials": "TJ", "orcid": "0000-0002-3034-4109", "researcher": {"href": "https://publications.scilifelab.se/researcher/46e55e31c134464c8d8f71cc553ef198.json"}}, {"family": "Filipovska", "given": "Aleksandra", "initials": "A", "orcid": "0000-0002-6998-8403", "researcher": {"href": "https://publications.scilifelab.se/researcher/c5130ef46efb4fcd8d3b7bbd5c1e7708.json"}}, {"family": "Larsson", "given": "Nils-G\u00f6ran", "initials": "NG", "orcid": "0000-0001-5100-996X", "researcher": {"href": "https://publications.scilifelab.se/researcher/1dc68aa2893a4ab8845fc32d8d6bc59a.json"}}, {"family": "Falkenberg", "given": "Maria", "initials": "M", "orcid": "0000-0001-8713-173X", "researcher": {"href": "https://publications.scilifelab.se/researcher/562109b99a5c4eb3bd8b92f30014828b.json"}}], "type": "journal article", "published": "2021-07-00", "journal": {"title": "Sci Adv", "issn": "2375-2548", "volume": "7", "issue": "27", "issn-l": "2375-2548"}, "abstract": "We report a role for the mitochondrial single-stranded DNA binding protein (mtSSB) in regulating mitochondrial DNA (mtDNA) replication initiation in mammalian mitochondria. Transcription from the light-strand promoter (LSP) is required both for gene expression and for generating the RNA primers needed for initiation of mtDNA synthesis. In the absence of mtSSB, transcription from LSP is strongly up-regulated, but no replication primers are formed. Using deep sequencing in a mouse knockout model and biochemical reconstitution experiments with pure proteins, we find that mtSSB is necessary to restrict transcription initiation to optimize RNA primer formation at both origins of mtDNA replication. Last, we show that human pathological versions of mtSSB causing severe mitochondrial disease cannot efficiently support primer formation and initiation of mtDNA replication.", "doi": "10.1126/sciadv.abf8631", "pmid": "34215584", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "7/27/eabf8631"}], "notes": [], "created": "2023-02-16T08:17:57.108Z", "modified": "2023-02-16T08:17:57.519Z"}, {"entity": "publication", "iuid": "5b76361099394032a6d0345aca9e350b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/5b76361099394032a6d0345aca9e350b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/5b76361099394032a6d0345aca9e350b"}}, "title": "The IgGFc-binding protein FCGBP is secreted with all GDPH sequences cleaved but maintained by interfragment disulfide bonds.", "authors": [{"family": "Ehrencrona", "given": "Erik", "initials": "E"}, {"family": "van der Post", "given": "Sjoerd", "initials": "S"}, {"family": "Gallego", "given": "Pablo", "initials": "P"}, {"family": "Recktenwald", "given": "Christian V", "initials": "CV"}, {"family": "Rodriguez-Pineiro", "given": "Ana M", "initials": "AM"}, {"family": "Garcia-Bonete", "given": "Maria-Jose", "initials": "MJ"}, {"family": "Trillo-Muyo", "given": "Sergio", "initials": "S"}, {"family": "B\u00e4ckstr\u00f6m", "given": "Malin", "initials": "M"}, {"family": "Hansson", "given": "Gunnar C", "initials": "GC"}, {"family": "Johansson", "given": "Malin E V", "initials": "MEV"}], "type": "journal article", "published": "2021-07-00", "journal": {"title": "J. Biol. Chem.", "issn": "1083-351X", "volume": "297", "issue": "1", "pages": "100871", "issn-l": "0021-9258"}, "abstract": "Mucus forms an important protective barrier that minimizes bacterial contact with the colonic epithelium. Intestinal mucus is organized in a complex network with several specific proteins, including the mucin-2 (MUC2) and the abundant IgGFc-binding protein, FCGBP. FCGBP is expressed in all intestinal goblet cells and is secreted into the mucus. It is comprised of repeated von Willebrand D (vWD) domain assemblies, most of which have a GDPH amino acid sequence that can be autocatalytically cleaved, as previously observed in the mucins MUC2 and mucin-5AC. However, the functions of FCGBP in the mucus are not understood. We show that all vWD domains of FCGBP with a GDPH sequence are cleaved and that these cleavages occur early during biosynthesis in the endoplasmic reticulum. All cleaved fragments, however, remain connected via a disulfide bond within each vWD domain. This cleavage generates a C-terminal-reactive Asp-anhydride that could react with other molecules, such as MUC2, but this was not observed. Quantitative analyses by MS showed that FCGBP was mainly soluble in chaotropic solutions, whereas MUC2 was insoluble, and most of the secreted FCGBP was not covalently bound to MUC2. Although FCGBP has been suggested to bind immunoglobulin G, we were unable to reproduce this binding in vitro using purified proteins. In conclusion, while the function of FCGBP is still unknown, our results suggest that it does not contribute to covalent crosslinking in the mucus, nor incorporate immunoglobulin G into mucus, instead the single disulfide bond linking each fragment could mediate controlled dissociation.", "doi": "10.1016/j.jbc.2021.100871", "pmid": "34126068", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8267560"}, {"db": "pii", "key": "S0021-9258(21)00671-2"}], "notes": [], "created": "2023-02-16T08:15:57.453Z", "modified": "2023-02-16T08:15:57.466Z"}, {"entity": "publication", "iuid": "adc8dc2ae99a4376a033098685b348a5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/adc8dc2ae99a4376a033098685b348a5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/adc8dc2ae99a4376a033098685b348a5"}}, "title": "Synthetic bacterial vesicles combined with tumour extracellular vesicles as cancer immunotherapy.", "authors": [{"family": "Park", "given": "Kyong-Su", "initials": "KS"}, {"family": "Svennerholm", "given": "Kristina", "initials": "K"}, {"family": "Crescitelli", "given": "Rossella", "initials": "R"}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C"}, {"family": "Gribonika", "given": "Inta", "initials": "I"}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J"}], "type": "journal article", "published": "2021-07-00", "journal": {"title": "J Extracell Vesicles", "issn": "2001-3078", "volume": "10", "issue": "9", "pages": "e12120", "issn-l": "2001-3078"}, "abstract": "Bacterial outer membrane vesicles (OMV) have gained attention as a promising new cancer vaccine platform for efficiently provoking immune responses. However, OMV induce severe toxicity by activating the innate immune system. In this study, we applied a simple isolation approach to produce artificial OMV that we have named Synthetic Bacterial Vesicles (SyBV) that do not induce a severe toxic response. We also explored the potential of SyBV as an immunotherapy combined with tumour extracellular vesicles to induce anti-tumour immunity. Bacterial SyBV were produced with high yield by a protocol including lysozyme and high pH treatment, resulting in pure vesicles with very few cytosolic components and no RNA or DNA. These SyBV did not cause systemic pro-inflammatory cytokine responses in mice compared to naturally released OMV. However, SyBV and OMV were similarly effective in activation of mouse bone marrow-derived dendritic cells. Co-immunization with SyBV and melanoma extracellular vesicles elicited tumour regression in melanoma-bearing mice through Th-1 type T cell immunity and balanced antibody production. Also, the immunotherapeutic effect of SyBV was synergistically enhanced by anti-PD-1 inhibitor. Moreover, SyBV displayed significantly greater adjuvant activity than other classical adjuvants. Taken together, these results demonstrate a safe and efficient strategy for eliciting specific anti-tumour responses using immunotherapeutic bacterial SyBV.", "doi": "10.1002/jev2.12120", "pmid": "34262675", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service", "Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8254025"}, {"db": "pii", "key": "JEV212120"}], "notes": [], "created": "2023-02-16T08:21:19.791Z", "modified": "2024-01-16T13:46:30.279Z"}, {"entity": "publication", "iuid": "ac498053fd134ab2a54ce6b4b2ed366c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ac498053fd134ab2a54ce6b4b2ed366c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ac498053fd134ab2a54ce6b4b2ed366c"}}, "title": "Following spatial A\u03b2 aggregation dynamics in evolving Alzheimer's disease pathology by imaging stable isotope labeling kinetics.", "authors": [{"family": "Michno", "given": "Wojciech", "initials": "W", "orcid": "0000-0002-3096-3604", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b4307eb6e45426e8176337e88c9c344.json"}}, {"family": "Stringer", "given": "Katie M", "initials": "KM", "orcid": "0000-0003-1616-2437", "researcher": {"href": "https://publications.scilifelab.se/researcher/c2638dd298ce470eb41bb45cbf1501c3.json"}}, {"family": "Enzlein", "given": "Thomas", "initials": "T", "orcid": "0000-0003-1789-4090", "researcher": {"href": "https://publications.scilifelab.se/researcher/8c32c7c836c4417182d0b04ac914e318.json"}}, {"family": "Passarelli", "given": "Melissa K", "initials": "MK", "orcid": "0000-0003-2466-1439", "researcher": {"href": "https://publications.scilifelab.se/researcher/2699b550e880407296571ccfe51a1cee.json"}}, {"family": "Escrig", "given": "Stephane", "initials": "S", "orcid": "0000-0002-7525-4000", "researcher": {"href": "https://publications.scilifelab.se/researcher/5f704fbd587f4a96b272ea9269512c89.json"}}, {"family": "Vitanova", "given": "Karina", "initials": "K", "orcid": "0000-0001-8800-4150", "researcher": {"href": "https://publications.scilifelab.se/researcher/c3c495f6ef37496fbafc13a93a8d50f3.json"}}, {"family": "Wood", "given": "Jack", "initials": "J", "orcid": "0000-0001-6049-4020", "researcher": {"href": "https://publications.scilifelab.se/researcher/a9b71cccc5da4ece9a9f57f0c46eda26.json"}}, {"family": "Blennow", "given": "Kaj", "initials": "K", "orcid": "0000-0002-1890-4193", "researcher": {"href": "https://publications.scilifelab.se/researcher/5e646be026ce42ecbfd4d62eca3f9bce.json"}}, {"family": "Zetterberg", "given": "Henrik", "initials": "H", "orcid": "0000-0003-3930-4354", "researcher": {"href": "https://publications.scilifelab.se/researcher/85efee74eb4a4b38b63cf2823d204529.json"}}, {"family": "Meibom", "given": "Anders", "initials": "A", "orcid": "0000-0002-4542-2819", "researcher": {"href": "https://publications.scilifelab.se/researcher/449ed37aa5ab48ab8b1d93e0ab0f3f9b.json"}}, {"family": "Hopf", "given": "Carsten", "initials": "C", "orcid": "0000-0003-0802-6451", "researcher": {"href": "https://publications.scilifelab.se/researcher/178878399aac4cd6bf793f3720c75365.json"}}, {"family": "Edwards", "given": "Frances A", "initials": "FA", "orcid": "0000-0001-8515-9077", "researcher": {"href": "https://publications.scilifelab.se/researcher/bdb5831ebd95409b9fc30c2410bf8ad3.json"}}, {"family": "Hanrieder", "given": "J\u00f6rg", "initials": "J", "orcid": "0000-0001-6059-198X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e65454100674f98bf8f2575093f2441.json"}}], "type": "journal article", "published": "2021-06-00", "journal": {"title": "Sci Adv", "issn": "2375-2548", "volume": "7", "issue": "25", "issn-l": "2375-2548"}, "abstract": "\u03b2-Amyloid (A\u03b2) plaque formation is the major pathological hallmark of Alzheimer's disease (AD) and constitutes a potentially critical, early inducer driving AD pathogenesis as it precedes other pathological events and cognitive symptoms by decades. It is therefore critical to understand how A\u03b2 pathology is initiated and where and when distinct A\u03b2 species aggregate. Here, we used metabolic isotope labeling in APP knock-in mice together with mass spectrometry imaging to monitor the earliest seeds of A\u03b2 deposition through ongoing plaque development. This allowed visualizing A\u03b2 aggregation dynamics within single plaques across different brain regions. We show that formation of structurally distinct plaques is associated with differential A\u03b2 peptide deposition. Specifically, A\u03b21-42 is forming an initial core structure followed by radial outgrowth and late secretion and deposition of A\u03b21-38. These data describe a detailed picture of the earliest events of precipitating amyloid pathology at scales not previously possible.NL-G-F", "doi": "10.1126/sciadv.abg4855", "pmid": "34134980", "labels": {"Integrated Microscopy Technologies Gothenburg": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC8208724"}, {"db": "pii", "key": "7/25/eabg4855"}], "notes": [], "created": "2023-02-16T08:19:47.219Z", "modified": "2023-02-16T08:19:47.531Z"}, {"entity": "publication", "iuid": "caea4faebcb54caa87a6da3f020aae84", "links": {"self": {"href": "https://publications.scilifelab.se/publication/caea4faebcb54caa87a6da3f020aae84.json"}, "display": {"href": "https://publications.scilifelab.se/publication/caea4faebcb54caa87a6da3f020aae84"}}, "title": "Association between Brachyspira and irritable bowel syndrome with diarrhoea.", "authors": [{"family": "Jabbar", "given": "Karolina S", "initials": "KS"}, {"family": "Dolan", "given": "Brendan", "initials": "B"}, {"family": "Eklund", "given": "Lisbeth", "initials": "L"}, {"family": "Wising", "given": "Catharina", "initials": "C"}, {"family": "Ermund", "given": "Anna", "initials": "A"}, {"family": "Johansson", "given": "\u00c5sa", "initials": "\u00c5"}, {"family": "T\u00f6rnblom", "given": "Hans", "initials": "H"}, {"family": "Simren", "given": "Magnus", "initials": "M"}, {"family": "Hansson", "given": "Gunnar C", "initials": "GC", "orcid": "0000-0002-1900-1869", "researcher": {"href": "https://publications.scilifelab.se/researcher/44b3815603154322a6dac16f2fc1c1e9.json"}}], "type": "journal article", "published": "2021-06-00", "journal": {"title": "Gut", "issn": "1468-3288", "volume": "70", "issue": "6", "pages": "1117-1129", "issn-l": "0017-5749"}, "abstract": "The incidence of IBS increases following enteric infections, suggesting a causative role for microbial imbalance. However, analyses of faecal microbiota have not demonstrated consistent alterations. Here, we used metaproteomics to investigate potential associations between mucus-resident microbiota and IBS symptoms.\n\nMucus samples were prospectively collected from sigmoid colon biopsies from patients with IBS and healthy volunteers, and their microbial protein composition analysed by mass spectrometry. Observations were verified by immunofluorescence, electron microscopy and real-time PCR, further confirmed in a second cohort, and correlated with comprehensive profiling of clinical characteristics and mucosal immune responses.\n\nMetaproteomic analysis of colon mucus samples identified peptides from potentially pathogenic Brachyspira species in a subset of patients with IBS. Using multiple diagnostic methods, mucosal Brachyspira colonisation was detected in a total of 19/62 (31%) patients with IBS from two prospective cohorts, versus 0/31 healthy volunteers (p<0.001). The prevalence of Brachyspira colonisation in IBS with diarrhoea (IBS-D) was 40% in both cohorts (p=0.02 and p=0.006 vs controls). Brachyspira attachment to the colonocyte apical membrane was observed in 20% of patients with IBS and associated with accelerated oro-anal transit, mild mucosal inflammation, mast cell activation and alterations of molecular pathways linked to bacterial uptake and ion-fluid homeostasis. Metronidazole treatment paradoxically promoted Brachyspira relocation into goblet cell secretory granules-possibly representing a novel bacterial strategy to evade antibiotics.\n\nMucosal Brachyspira colonisation was significantly more common in IBS and associated with distinctive clinical, histological and molecular characteristics. Our observations suggest a role for Brachyspira in the pathogenesis of IBS, particularly IBS-D.", "doi": "10.1136/gutjnl-2020-321466", "pmid": "33177165", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8108289"}, {"db": "pii", "key": "gutjnl-2020-321466"}], "notes": [], "created": "2023-02-16T08:07:34.470Z", "modified": "2023-02-16T08:18:07.798Z"}, {"entity": "publication", "iuid": "c4022feddc994116a9dfc29573ac204a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c4022feddc994116a9dfc29573ac204a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c4022feddc994116a9dfc29573ac204a"}}, "title": "Towards a bioengineered uterus: bioactive sheep uterus scaffolds are effectively recellularized by enzymatic preconditioning.", "authors": [{"family": "Padma", "given": "Arvind Manikantan", "initials": "AM"}, {"family": "Carri\u00e8re", "given": "Laura", "initials": "L", "orcid": "0000-0001-9639-9594", "researcher": {"href": "https://publications.scilifelab.se/researcher/58c162e0fcbd49028a2d155433969c6c.json"}}, {"family": "Krokstr\u00f6m Karlsson", "given": "Frida", "initials": "F"}, {"family": "Sehic", "given": "Edina", "initials": "E"}, {"family": "Bandstein", "given": "Sara", "initials": "S"}, {"family": "Tiemann", "given": "Tom Tristan", "initials": "TT"}, {"family": "Oltean", "given": "Mihai", "initials": "M"}, {"family": "Song", "given": "Min Jong", "initials": "MJ"}, {"family": "Br\u00e4nnstr\u00f6m", "given": "Mats", "initials": "M"}, {"family": "Hellstr\u00f6m", "given": "Mats", "initials": "M", "orcid": "0000-0003-3323-5618", "researcher": {"href": "https://publications.scilifelab.se/researcher/b41c54e9336c444d9de92c43a3330c9e.json"}}], "type": "journal article", "published": "2021-05-21", "journal": {"title": "NPJ Regen Med", "issn": "2057-3995", "volume": "6", "issue": "1", "pages": "26", "issn-l": null}, "abstract": "Uterine factor infertility was considered incurable until recently when we reported the first successful live birth after uterus transplantation. However, risky donor surgery and immunosuppressive therapy are factors that may be avoided with bioengineering. For example, transplanted recellularized constructs derived from decellularized tissue restored fertility in rodent models and mandate translational studies. In this study, we decellularized whole sheep uterus with three different protocols using 0.5% sodium dodecyl sulfate, 2% sodium deoxycholate (SDC) or 2% SDC, and 1% Triton X-100. Scaffolds were then assessed for bioactivity using the dorsal root ganglion and chorioallantoic membrane assays, and we found that all the uterus scaffolds exhibited growth factor activity that promoted neurogenesis and angiogenesis. Extensive recellularization optimization was conducted using multipotent sheep fetal stem cells and we report results from the following three in vitro conditions; (a) standard cell culturing conditions, (b) constructs cultured in transwells, and (c) scaffolds preconditioned with matrix metalloproteinase 2 and 9. The recellularization efficiency was improved short-term when transwells were used compared with standard culturing conditions. However, the recellularization efficiency in scaffolds preconditioned with matrix metalloproteinases was 200-300% better than the other strategies evaluated herein, independent of decellularization protocol. Hence, a major recellularization hurdle has been overcome with the improved recellularization strategies and in vitro platforms described herein. These results are an important milestone and should facilitate the production of large bioengineered grafts suitable for future in vivo applications in the sheep, which is an essential step before considering these principles in a clinical setting.", "doi": "10.1038/s41536-021-00136-0", "pmid": "34021161", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8140118"}, {"db": "pii", "key": "10.1038/s41536-021-00136-0"}], "notes": [], "created": "2023-02-16T08:21:27.788Z", "modified": "2023-02-16T08:21:27.859Z"}, {"entity": "publication", "iuid": "c9ebacd9c7234693a7d43f3106e6f521", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c9ebacd9c7234693a7d43f3106e6f521.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c9ebacd9c7234693a7d43f3106e6f521"}}, "title": "Highly Permeable Fluorinated Polymer Nanocomposites for Plasmonic Hydrogen Sensing.", "authors": [{"family": "\u00d6stergren", "given": "Ida", "initials": "I", "orcid": "0000-0002-2431-0746", "researcher": {"href": "https://publications.scilifelab.se/researcher/969b5508235e4e14a7654c71cb426bb1.json"}}, {"family": "Pourrahimi", "given": "Amir Masoud", "initials": "AM", "orcid": "0000-0001-5867-0531", "researcher": {"href": "https://publications.scilifelab.se/researcher/3c667e9cb1654493af7c86f1d553c427.json"}}, {"family": "Darmadi", "given": "Iwan", "initials": "I", "orcid": "0000-0002-5921-9336", "researcher": {"href": "https://publications.scilifelab.se/researcher/d24542fa29854812a58bc1906bdeaf8a.json"}}, {"family": "da Silva", "given": "Robson", "initials": "R"}, {"family": "Stola\u015b", "given": "Alicja", "initials": "A", "orcid": "0000-0002-6736-9553", "researcher": {"href": "https://publications.scilifelab.se/researcher/f882b7702b204bc88c1e7a81b9554194.json"}}, {"family": "Lerch", "given": "Sarah", "initials": "S", "orcid": "0000-0001-5968-8178", "researcher": {"href": "https://publications.scilifelab.se/researcher/e192f96f7cb74b96985567fa2c099bf1.json"}}, {"family": "Berke", "given": "Barbara", "initials": "B", "orcid": "0000-0002-3105-2036", "researcher": {"href": "https://publications.scilifelab.se/researcher/b7e866bd004143959951261606413e8f.json"}}, {"family": "Guizar-Sicairos", "given": "Manuel", "initials": "M"}, {"family": "Liebi", "given": "Marianne", "initials": "M", "orcid": "0000-0002-5403-0593", "researcher": {"href": "https://publications.scilifelab.se/researcher/a404e64ffe7c47e0ac15819102c38279.json"}}, {"family": "Foli", "given": "Giacomo", "initials": "G"}, {"family": "Palermo", "given": "Vincenzo", "initials": "V"}, {"family": "Minelli", "given": "Matteo", "initials": "M", "orcid": "0000-0003-4662-1526", "researcher": {"href": "https://publications.scilifelab.se/researcher/44301a57b0704c90b546a7ef985dd73e.json"}}, {"family": "Moth-Poulsen", "given": "Kasper", "initials": "K", "orcid": "0000-0003-4018-4927", "researcher": {"href": "https://publications.scilifelab.se/researcher/5807cc241ba24cf4a7841086d72dc3b9.json"}}, {"family": "Langhammer", "given": "Christoph", "initials": "C", "orcid": "0000-0003-2180-1379", "researcher": {"href": "https://publications.scilifelab.se/researcher/17178716c3964e53933ddacffe70cc9a.json"}}, {"family": "M\u00fcller", "given": "Christian", "initials": "C", "orcid": "0000-0001-7859-7909", "researcher": {"href": "https://publications.scilifelab.se/researcher/7fc06198eb0c4a3eb17d052d8ef124ae.json"}}], "type": "journal article", "published": "2021-05-12", "journal": {"title": "ACS Appl Mater Interfaces", "issn": "1944-8252", "volume": "13", "issue": "18", "pages": "21724-21732", "issn-l": "1944-8244"}, "abstract": "Hydrogen (H2) sensors that can be produced en masse with cost-effective manufacturing tools are critical for enabling safety in the emerging hydrogen economy. The use of melt-processed nanocomposites in this context would allow the combination of the advantages of plasmonic hydrogen detection with polymer technology; an approach which is held back by the slow diffusion of H2 through the polymer matrix. Here, we show that the use of an amorphous fluorinated polymer, compounded with colloidal Pd nanoparticles prepared by highly scalable continuous flow synthesis, results in nanocomposites that display a high H2 diffusion coefficient in the order of 10-5 cm2 s-1. As a result, plasmonic optical hydrogen detection with melt-pressed fluorinated polymer nanocomposites is no longer limited by the diffusion of the H2 analyte to the Pd nanoparticle transducer elements, despite a thickness of up to 100 \u03bcm, thereby enabling response times as short as 2.5 s at 100 mbar (\u226110 vol. %) H2. Evidently, plasmonic sensors with a fast response time can be fabricated with thick, melt-processed nanocomposites, which paves the way for a new generation of robust H2 sensors.", "doi": "10.1021/acsami.1c01968", "pmid": "33909392", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8289187"}], "notes": [], "created": "2023-02-16T08:22:49.632Z", "modified": "2023-02-16T08:22:49.760Z"}, {"entity": "publication", "iuid": "d77e5ffa3ce742b99fbd970f63788646", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d77e5ffa3ce742b99fbd970f63788646.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d77e5ffa3ce742b99fbd970f63788646"}}, "title": "An amylin and calcitonin receptor agonist modulates alcohol behaviors by acting on reward-related areas in the brain.", "authors": [{"family": "Kalafateli", "given": "Aimilia Lydia", "initials": "AL"}, {"family": "Satir", "given": "Tugce Munise", "initials": "TM"}, {"family": "Vall\u00f6f", "given": "Daniel", "initials": "D"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H"}, {"family": "Jerlhag", "given": "Elisabet", "initials": "E"}], "type": "journal article", "published": "2021-05-00", "journal": {"title": "Prog Neurobiol", "issn": "1873-5118", "volume": "200", "pages": "101969", "issn-l": null}, "abstract": "Alcohol causes stimulatory behavioral responses by activating reward-processing brain areas including the laterodorsal (LDTg) and ventral tegmental areas (VTA) and the nucleus accumbens (NAc). Systemic administration of the amylin and calcitonin receptor agonist salmon calcitonin (sCT) attenuates alcohol-mediated behaviors, but the brain sites involved in this process remain unknown. Firstly, to identify potential sCT sites of action in the brain, we used immunohistochemistry after systemic administration of fluorescent-labeled sCT. We then performed behavioral experiments to explore how infused sCT into the aforementioned reward-processing brain areas affects acute alcohol-induced behaviors in mice and chronic alcohol consumption in rats. We show that peripheral sCT crosses the blood brain barrier and is detected in all the brain areas studied herein. sCT infused into the LDTg attenuates alcohol-evoked dopamine release in the NAc shell in mice and reduces alcohol intake in rats. sCT into the VTA blocks alcohol-induced locomotor stimulation and dopamine release in the NAc shell in mice and decreases alcohol intake in rats. Lastly, sCT into the NAc shell prevents alcohol-induced locomotor activity in mice. Our data suggest that central sCT modulates the ability of alcohol to activate reward-processing brain regions.", "doi": "10.1016/j.pneurobio.2020.101969", "pmid": "33278524", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S0301-0082(20)30224-0"}], "notes": [], "created": "2023-02-16T08:18:21.481Z", "modified": "2023-02-16T08:18:21.552Z"}, {"entity": "publication", "iuid": "2b54f0133c7b43f9801e3f8e05389752", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2b54f0133c7b43f9801e3f8e05389752.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2b54f0133c7b43f9801e3f8e05389752"}}, "title": "Cryo-Electron Microscopy of Arabidopsis thaliana Phytochrome A in Its Pr State Reveals Head-to-Head Homodimeric Architecture.", "authors": [{"family": "Wahlgren", "given": "Weixiao Yuan", "initials": "WY"}, {"family": "Golonka", "given": "David", "initials": "D"}, {"family": "Westenhoff", "given": "Sebastian", "initials": "S", "orcid": "0000-0002-6961-8015", "researcher": {"href": "https://publications.scilifelab.se/researcher/3f1519bb234b43c6a13833b04e6720b8.json"}}, {"family": "M\u00f6glich", "given": "Andreas", "initials": "A"}], "type": "journal article", "published": "2021-04-21", "journal": {"title": "Front Plant Sci", "issn": "1664-462X", "volume": "12", "pages": "663751", "issn-l": "1664-462X"}, "abstract": "Phytochrome photoreceptors regulate vital adaptations of plant development, growth, and physiology depending on the ratio of red and far-red light. The light-triggered Z/E isomerization of a covalently bound bilin chromophore underlies phytochrome photoconversion between the red-absorbing Pr and far-red-absorbing Pfr states. Compared to bacterial phytochromes, the molecular mechanisms of signal propagation to the C-terminal module and its regulation are little understood in plant phytochromes, not least owing to a dearth of structural information. To address this deficit, we studied the Arabidopsis thaliana phytochrome A (AtphyA) at full length by cryo-electron microscopy (cryo-EM). Following heterologous expression in Escherichia coli, we optimized the solvent conditions to overcome protein aggregation and thus obtained photochemically active, near-homogenous AtphyA. We prepared grids for cryo-EM analysis of AtphyA in its Pr state and conducted single-particle analysis. The resulting two-dimensional class averages and the three-dimensional electron density map at 17 \u00c5 showed a homodimeric head-to-head assembly of AtphyA. Docking of domain structures into the electron density revealed a separation of the AtphyA homodimer at the junction of its photosensor and effector modules, as reflected in a large void in the middle of map. The overall architecture of AtphyA resembled that of bacterial phytochromes, thus hinting at commonalities in signal transduction and mechanism between these receptors. Our work paves the way toward future studies of the structure, light response, and interactions of full-length phytochromes by cryo-EM.", "doi": "10.3389/fpls.2021.663751", "pmid": "34108981", "labels": {"Cryo-EM": "Service", "Integrated Microscopy Technologies Gothenburg": "Technology development"}, "xrefs": [{"db": "pmc", "key": "PMC8182759"}], "notes": [], "created": "2021-12-14T12:25:21.473Z", "modified": "2023-12-04T10:16:21.768Z"}, {"entity": "publication", "iuid": "a27ec54fcc1c4fcfa2ee0463e3b004a0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a27ec54fcc1c4fcfa2ee0463e3b004a0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a27ec54fcc1c4fcfa2ee0463e3b004a0"}}, "title": "Alternative redox forms of ASNA-1 separate insulin signaling from tail-anchored protein targeting and cisplatin resistance in C. elegans.", "authors": [{"family": "Raj", "given": "Dorota", "initials": "D"}, {"family": "Billing", "given": "Ola", "initials": "O"}, {"family": "Podraza-Farhanieh", "given": "Agnieszka", "initials": "A"}, {"family": "Kraish", "given": "Bashar", "initials": "B"}, {"family": "Hemmingsson", "given": "Oskar", "initials": "O"}, {"family": "Kao", "given": "Gautam", "initials": "G"}, {"family": "Naredi", "given": "Peter", "initials": "P"}], "type": "journal article", "published": "2021-04-21", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "11", "issue": "1", "pages": "8678", "issn-l": "2045-2322"}, "abstract": "Cisplatin is a frontline cancer therapeutic, but intrinsic or acquired resistance is common. We previously showed that cisplatin sensitivity can be achieved by inactivation of ASNA-1/TRC40 in mammalian cancer cells and in Caenorhabditis elegans. ASNA-1 has two more conserved functions: in promoting tail-anchored protein (TAP) targeting to the endoplasmic reticulum membrane and in promoting insulin secretion. However, the relation between its different functions has remained unknown. Here, we show that ASNA-1 exists in two redox states that promote TAP-targeting and insulin secretion separately. The reduced state is the one required for cisplatin resistance: an ASNA-1 point mutant, in which the protein preferentially was found in the oxidized state, was sensitive to cisplatin and defective for TAP targeting but had no insulin secretion defect. The same was true for mutants in wrb-1, which we identify as the C. elegans homolog of WRB, the ASNA1/TRC40 receptor. Finally, we uncover a previously unknown action of cisplatin induced reactive oxygen species: cisplatin induced ROS drives ASNA-1 into the oxidized form, and selectively prevents an ASNA-1-dependent TAP substrate from reaching the endoplasmic reticulum. Our work suggests that ASNA-1 acts as a redox-sensitive target for cisplatin cytotoxicity and that cisplatin resistance is likely mediated by ASNA-1-dependent TAP substrates. Treatments that promote an oxidizing tumor environment should be explored as possible means to combat cisplatin resistance.", "doi": "10.1038/s41598-021-88085-y", "pmid": "33883621", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8060345"}, {"db": "pii", "key": "10.1038/s41598-021-88085-y"}], "notes": [], "created": "2023-02-16T08:21:59.374Z", "modified": "2023-02-16T08:21:59.388Z"}, {"entity": "publication", "iuid": "cfee2a078b7e401abfb41e4ec8b07fe7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cfee2a078b7e401abfb41e4ec8b07fe7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cfee2a078b7e401abfb41e4ec8b07fe7"}}, "title": "An intercrypt subpopulation of goblet cells is essential for colonic mucus barrier function.", "authors": [{"family": "Nystr\u00f6m", "given": "Elisabeth E L", "initials": "EEL", "orcid": "0000-0002-6970-7894", "researcher": {"href": "https://publications.scilifelab.se/researcher/09bd302f8a1341f6a1a5aaf3bfe94a94.json"}}, {"family": "Martinez-Abad", "given": "Beatriz", "initials": "B", "orcid": "0000-0002-0521-3473", "researcher": {"href": "https://publications.scilifelab.se/researcher/2d3781ca1b0245908c2030b4707cc34d.json"}}, {"family": "Arike", "given": "Liisa", "initials": "L", "orcid": "0000-0002-2184-0960", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a6ecb751dca49a598e3d13cc92ee5cf.json"}}, {"family": "Birchenough", "given": "George M H", "initials": "GMH", "orcid": "0000-0003-2283-2353", "researcher": {"href": "https://publications.scilifelab.se/researcher/aecb4d51bffc490d87b0a4fffb7de59a.json"}}, {"family": "Nonnecke", "given": "Eric B", "initials": "EB", "orcid": "0000-0001-5345-2009", "researcher": {"href": "https://publications.scilifelab.se/researcher/bc51bb370f354fa18d7aa7fa6181e316.json"}}, {"family": "Castillo", "given": "Patricia A", "initials": "PA", "orcid": "0000-0001-5007-9026", "researcher": {"href": "https://publications.scilifelab.se/researcher/8437b4ec27604a49965792fb392c7202.json"}}, {"family": "Svensson", "given": "Frida", "initials": "F", "orcid": "0000-0003-0397-804X", "researcher": {"href": "https://publications.scilifelab.se/researcher/34e2f316531a41f5b2a349253d36453f.json"}}, {"family": "Bevins", "given": "Charles L", "initials": "CL", "orcid": "0000-0003-2725-2622", "researcher": {"href": "https://publications.scilifelab.se/researcher/69d07c700bee47a098d13b8872dad519.json"}}, {"family": "Hansson", "given": "Gunnar C", "initials": "GC", "orcid": "0000-0002-1900-1869", "researcher": {"href": "https://publications.scilifelab.se/researcher/44b3815603154322a6dac16f2fc1c1e9.json"}}, {"family": "Johansson", "given": "Malin E V", "initials": "MEV", "orcid": "0000-0002-4237-6677", "researcher": {"href": "https://publications.scilifelab.se/researcher/520dab35c19049c8b3f1083a92e60d56.json"}}], "type": "journal article", "published": "2021-04-16", "journal": {"title": "Science", "issn": "1095-9203", "volume": "372", "issue": "6539", "issn-l": "0036-8075"}, "abstract": "The intestinal mucus layer, an important element of epithelial protection, is produced by goblet cells. Intestinal goblet cells are assumed to be a homogeneous cell type. In this study, however, we delineated their specific gene and protein expression profiles and identified several distinct goblet cell populations that form two differentiation trajectories. One distinct subtype, the intercrypt goblet cells (icGCs), located at the colonic luminal surface, produced mucus with properties that differed from the mucus secreted by crypt-residing goblet cells. Mice with defective icGCs had increased sensitivity to chemically induced colitis and manifested spontaneous colitis with age. Furthermore, alterations in mucus and reduced numbers of icGCs were observed in patients with both active and remissive ulcerative colitis, which highlights the importance of icGCs in maintaining functional protection of the epithelium.", "doi": "10.1126/science.abb1590", "pmid": "33859001", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "mid", "key": "NIHMS1738550"}, {"db": "pmc", "key": "PMC8542866"}, {"db": "pii", "key": "372/6539/eabb1590"}], "notes": [], "created": "2023-02-16T08:20:46.634Z", "modified": "2023-02-16T08:20:46.839Z"}, {"entity": "publication", "iuid": "725edebcf7394ac8a292d10f91b7c3a6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/725edebcf7394ac8a292d10f91b7c3a6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/725edebcf7394ac8a292d10f91b7c3a6"}}, "title": "The C. elegans PAQR-2 and IGLR-2 membrane homeostasis proteins are uniquely essential for tolerating dietary saturated fats.", "authors": [{"family": "Devkota", "given": "Ranjan", "initials": "R"}, {"family": "Henricsson", "given": "Marcus", "initials": "M"}, {"family": "Bor\u00e9n", "given": "Jan", "initials": "J"}, {"family": "Pilon", "given": "Marc", "initials": "M"}], "type": "journal article", "published": "2021-04-00", "journal": {"title": "Biochim Biophys Acta Mol Cell Biol Lipids", "issn": "1879-2618", "volume": "1866", "issue": "4", "pages": "158883", "issn-l": null}, "abstract": "How cells maintain vital membrane lipid homeostasis while obtaining most of their constituent fatty acids from a varied diet remains largely unknown. Here, we report the first whole-organism (Caenorhabditis elegans) forward genetic screen to identify genes essential for tolerance to dietary saturated fatty acids (SFAs). We found that only the PAQR-2/IGLR-2 pathway, homologous to the human adiponectin receptor 2 (AdipoR2) pathway, is uniquely essential to prevent SFA-mediated toxicity. When provided a SFA-rich diet, worms lacking either protein accumulate an excess of SFAs in their membrane phospholipids, which is accompanied by membrane rigidification. Additionally, we used fluorescence resonance energy transfer (FRET) to show that the interaction between PAQR-2 and IGLR-2 is regulated by membrane fluidity, suggesting a mechanism by which this protein complex senses membrane properties. We also created versions of PAQR-2 that lacked parts of the cytoplasmic N-terminal domain and showed that these were still functional, though still dependent on the interaction with IGLR-2. We conclude that membrane homeostasis via the PAQR-2/IGLR-2 fluidity sensor is the only pathway specifically essential for the non-toxic uptake of dietary SFAs in C. elegans.", "doi": "10.1016/j.bbalip.2021.158883", "pmid": "33444761", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S1388-1981(21)00009-3"}], "notes": [], "created": "2023-02-16T08:15:26.101Z", "modified": "2023-02-16T08:15:26.130Z"}, {"entity": "publication", "iuid": "f2d9ecae73c44d238c01ab6c6878d296", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f2d9ecae73c44d238c01ab6c6878d296.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f2d9ecae73c44d238c01ab6c6878d296"}}, "title": "LY6K-AS lncRNA is a lung adenocarcinoma prognostic biomarker and regulator of mitotic progression.", "authors": [{"family": "Ali", "given": "Mohamad Moustafa", "initials": "MM"}, {"family": "Di Marco", "given": "Mirco", "initials": "M", "orcid": "0000-0001-8890-233X", "researcher": {"href": "https://publications.scilifelab.se/researcher/8406c87db9604c1e863736eb7bd11bf1.json"}}, {"family": "Mahale", "given": "Sagar", "initials": "S"}, {"family": "Jachimowicz", "given": "Daniel", "initials": "D"}, {"family": "Kosalai", "given": "Subazini Thankaswamy", "initials": "ST"}, {"family": "Reischl", "given": "Silke", "initials": "S", "orcid": "0000-0003-4822-4137", "researcher": {"href": "https://publications.scilifelab.se/researcher/bf139e277ad14d7caf0bfe88ef9f34d2.json"}}, {"family": "Statello", "given": "Luisa", "initials": "L"}, {"family": "Mishra", "given": "Kankadeb", "initials": "K"}, {"family": "Darnfors", "given": "Catarina", "initials": "C"}, {"family": "Kanduri", "given": "Meena", "initials": "M"}, {"family": "Kanduri", "given": "Chandrasekhar", "initials": "C", "orcid": "0000-0001-6271-9078", "researcher": {"href": "https://publications.scilifelab.se/researcher/a8da9c5c5d0c48f9ae08549027375512.json"}}], "type": "journal article", "published": "2021-04-00", "journal": {"title": "Oncogene", "issn": "1476-5594", "volume": "40", "issue": "13", "pages": "2463-2478", "issn-l": "0950-9232"}, "abstract": "Recent advances in genomics unraveled several actionable mutational drivers in lung cancer, leading to promising therapies such as tyrosine kinase inhibitors and immune checkpoint inhibitors. However, the tumors' acquired resistance to the newly-developed as well as existing therapies restricts life quality improvements. Therefore, we investigated the noncoding portion of the human transcriptome in search of alternative actionable targets. We identified an antisense transcript, LY6K-AS, with elevated expression in lung adenocarcinoma (LUAD) patients, and its higher expression in LUAD patients predicts poor survival outcomes. LY6K-AS abrogation interfered with the mitotic progression of lung cancer cells resulting in unfaithful chromosomal segregation. LY6K-AS interacts with and stabilizes 14-3-3 proteins to regulate the transcription of kinetochore and mitotic checkpoint proteins. We also show that LY6K-AS regulates the levels of histone H3 lysine 4 trimethylation (H3K4me3) at the promoters of kinetochore members. Cisplatin treatment and LY6K-AS silencing affect many common pathways enriched in cell cycle-related functions. LY6K-AS silencing affects the growth of xenografts derived from wildtype and cisplatin-resistant lung cancer cells. Collectively, these data indicate that LY6K-AS silencing is a promising therapeutic option for LUAD that inhibits oncogenic mitotic progression.", "doi": "10.1038/s41388-021-01696-7", "pmid": "33674747", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41388-021-01696-7"}], "notes": [], "created": "2023-02-16T08:13:43.139Z", "modified": "2023-02-16T08:13:43.241Z"}, {"entity": "publication", "iuid": "9961468d3d244360bd3a8c90c33f6899", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9961468d3d244360bd3a8c90c33f6899.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9961468d3d244360bd3a8c90c33f6899"}}, "title": "Extensive transcription mis-regulation and membrane defects in AdipoR2-deficient cells challenged with saturated fatty acids.", "authors": [{"family": "Ruiz", "given": "Mario", "initials": "M"}, {"family": "Palmgren", "given": "Henrik", "initials": "H"}, {"family": "Henricsson", "given": "Marcus", "initials": "M"}, {"family": "Devkota", "given": "Ranjan", "initials": "R"}, {"family": "Jaiswal", "given": "Himjyot", "initials": "H"}, {"family": "Maresca", "given": "Marcello", "initials": "M"}, {"family": "Bohlooly-Y", "given": "Mohammad", "initials": "M"}, {"family": "Peng", "given": "Xiao-Rong", "initials": "XR"}, {"family": "Bor\u00e9n", "given": "Jan", "initials": "J"}, {"family": "Pilon", "given": "Marc", "initials": "M"}], "type": "journal article", "published": "2021-04-00", "journal": {"title": "Biochim Biophys Acta Mol Cell Biol Lipids", "issn": "1879-2618", "volume": "1866", "issue": "4", "pages": "158884", "issn-l": null}, "abstract": "How cells maintain vital membrane lipid homeostasis while obtaining most of their constituent fatty acids from a varied diet remains largely unknown. Here, we used transcriptomics, lipidomics, growth and respiration assays, and membrane property analyses in human HEK293 cells or human umbilical vein endothelial cells (HUVEC) to show that the function of AdipoR2 is to respond to membrane rigidification by regulating many lipid metabolism genes. We also show that AdipoR2-dependent membrane homeostasis is critical for growth and respiration in cells challenged with saturated fatty acids. Additionally, we found that AdipoR2 deficiency causes transcriptome and cell physiological defects similar to those observed in SREBP-deficient cells upon SFA challenge. Finally, we compared several genes considered important for lipid homeostasis, namely AdipoR2, SCD, FADS2, PEMT and ACSL4, and found that AdipoR2 and SCD are the most important among these to prevent membrane rigidification and excess saturation when human cells are challenged with exogenous SFAs. We conclude that AdipoR2-dependent membrane homeostasis is one of the primary mechanisms that protects against exogenous SFAs.", "doi": "10.1016/j.bbalip.2021.158884", "pmid": "33444759", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S1388-1981(21)00010-X"}], "notes": [], "created": "2023-02-16T08:22:06.867Z", "modified": "2023-02-16T08:22:06.878Z"}, {"entity": "publication", "iuid": "adc9079acc3040a69b2eba909277584d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/adc9079acc3040a69b2eba909277584d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/adc9079acc3040a69b2eba909277584d"}}, "title": "TLR4-Associated IRF-7 and NF\u03baB Signaling Act as a Molecular Link Between Androgen and Metformin Activities and Cytokine Synthesis in the PCOS Endometrium.", "authors": [{"family": "Hu", "given": "Min", "initials": "M"}, {"family": "Zhang", "given": "Yuehui", "initials": "Y"}, {"family": "Li", "given": "Xin", "initials": "X"}, {"family": "Cui", "given": "Peng", "initials": "P"}, {"family": "Sferruzzi-Perri", "given": "Amanda Nancy", "initials": "AN"}, {"family": "Br\u00e4nnstr\u00f6m", "given": "Mats", "initials": "M"}, {"family": "Shao", "given": "Linus R", "initials": "LR"}, {"family": "Billig", "given": "H\u00e5kan", "initials": "H"}], "type": "journal article", "published": "2021-03-25", "journal": {"title": "J. Clin. Endocrinol. Metab.", "issn": "1945-7197", "volume": "106", "issue": "4", "pages": "1022-1040", "issn-l": "0021-972X"}, "abstract": "Low-grade chronic inflammation is commonly seen in polycystic ovary syndrome (PCOS) patients with elevated levels of inflammatory cytokines in the endometrium.\n\nThis work aimed to increase the limited understanding of the mechanisms underlying cytokine synthesis and increased endometrial inflammation in PCOS patients.\n\nEndometrial biopsy samples were collected from non-PCOS (n = 17) and PCOS (n = 22) patients either during the proliferative phase of the menstrual cycle or with hyperplasia. Endometrial explants were prepared from PCOS patients and underwent pharmacological manipulation in vitro. The expression and localization of toll-like receptor 2 (TLR2)/4, key elements of innate immune signal transduction and nuclear factor \u03baB (NF\u03baB) signaling pathways, and multiple cytokines were comprehensively evaluated by Western blotting, immunohistochemistry, and immunofluorescence in endometrial tissues.\n\nWe demonstrated the distribution of protein expression and localization associated with the significantly increased androgen receptor, TLR2, and TLR4-mediated activation of interferon regulatory factor-7 (IRF-7) and NF\u03baB signaling, cytokine production, and endometrial inflammation in PCOS patients compared to non-PCOS patients with and without endometrial hyperplasia. In vitro experiments showed that 5-dihydrotestosterone (DHT) enhanced androgen receptor, TLR4, IRF-7, and p-NF\u03baB p65 protein expression along with increased interferon \u03b1 (IFN\u03b1) and IFN\u0263 abundance. The effects of DHT on IRF-7, p-NF\u03baB p65, and IFN abundance were abolished by flutamide, an antiandrogen. Although 17\u03b2-estradiol (E2) decreased p-IRF-7 expression with little effect on TLR-mediated IRF7 and NF\u03baB signaling or on cytokine protein levels, exposure to metformin alone or in combination with E2 suppressed interleukin-1 receptor-associated kinase 4 (IRAK4), p-IRF-7, IRF-7, I\u03baB kinase \u03b1 (IKK\u03b1), p-NF\u03baB p65, IFN\u0263, and tumor necrosis factor \u03b1 protein expression.\n\nCytokine synthesis and increased endometrial inflammation in PCOS patients are coupled to androgen-induced TLR4/IRF-7/NF\u03baB signaling, which is inhibited by metformin treatment.", "doi": "10.1210/clinem/dgaa951", "pmid": "33382900", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "6056640"}], "notes": [], "created": "2023-02-16T08:16:53.960Z", "modified": "2023-02-16T08:16:53.974Z"}, {"entity": "publication", "iuid": "6b0b02388e634b52a0ae523970b9cdb4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6b0b02388e634b52a0ae523970b9cdb4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6b0b02388e634b52a0ae523970b9cdb4"}}, "title": "Dynamics of Ku and bacterial non-homologous end-joining characterized using single DNA molecule analysis.", "authors": [{"family": "\u00d6z", "given": "Robin", "initials": "R"}, {"family": "Wang", "given": "Jing L", "initials": "JL"}, {"family": "Guerois", "given": "Raphael", "initials": "R"}, {"family": "Goyal", "given": "Gaurav", "initials": "G"}, {"family": "Kk", "given": "Sriram", "initials": "S"}, {"family": "Ropars", "given": "Virginie", "initials": "V"}, {"family": "Sharma", "given": "Rajhans", "initials": "R"}, {"family": "Koca", "given": "Firat", "initials": "F"}, {"family": "Charbonnier", "given": "Jean-Baptiste", "initials": "JB"}, {"family": "Modesti", "given": "Mauro", "initials": "M"}, {"family": "Strick", "given": "Terence R", "initials": "TR"}, {"family": "Westerlund", "given": "Fredrik", "initials": "F"}], "type": "journal article", "published": "2021-03-18", "journal": {"title": "Nucleic Acids Res.", "issn": "1362-4962", "volume": "49", "issue": "5", "pages": "2629-2641", "issn-l": "0305-1048"}, "abstract": "We use single-molecule techniques to characterize the dynamics of prokaryotic DNA repair by non-homologous end-joining (NHEJ), a system comprised only of the dimeric Ku and Ligase D (LigD). The Ku homodimer alone forms a \u223c2 s synapsis between blunt DNA ends that is increased to \u223c18 s upon addition of LigD, in a manner dependent on the C-terminal arms of Ku. The synapsis lifetime increases drastically for 4 nt complementary DNA overhangs, independently of the C-terminal arms of Ku. These observations are in contrast to human Ku, which is unable to bridge either of the two DNA substrates. We also demonstrate that bacterial Ku binds the DNA ends in a cooperative manner for synapsis initiation and remains stably bound at DNA junctions for several hours after ligation is completed, indicating that a system for removal of the proteins is active in vivo. Together these experiments shed light on the dynamics of bacterial NHEJ in DNA end recognition and processing. We speculate on the evolutionary similarities between bacterial and eukaryotic NHEJ and discuss how an increased understanding of bacterial NHEJ can open the door for future antibiotic therapies targeting this mechanism.", "doi": "10.1093/nar/gkab083", "pmid": "33590005", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7969030"}, {"db": "pii", "key": "6137296"}], "notes": [], "created": "2023-02-16T08:21:10.752Z", "modified": "2023-02-16T08:22:38.560Z"}, {"entity": "publication", "iuid": "09d2700c84de43ee87e845e090c22761", "links": {"self": {"href": "https://publications.scilifelab.se/publication/09d2700c84de43ee87e845e090c22761.json"}, "display": {"href": "https://publications.scilifelab.se/publication/09d2700c84de43ee87e845e090c22761"}}, "title": "Isolation and characterization of extracellular vesicle subpopulations from tissues.", "authors": [{"family": "Crescitelli", "given": "Rossella", "initials": "R", "orcid": "0000-0002-1714-3169", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d4b955f26ca4a679deb090e30d0ccf1.json"}}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C", "orcid": "0000-0003-1279-1746", "researcher": {"href": "https://publications.scilifelab.se/researcher/e14e17d2cdb24a9f93991d83811c78b9.json"}}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J"}], "type": "journal article", "published": "2021-03-00", "journal": {"title": "Nat Protoc", "issn": "1750-2799", "volume": "16", "issue": "3", "pages": "1548-1580", "issn-l": null}, "abstract": "Extracellular vesicles (EVs) are lipid bilayered membrane structures released by all cells. Most EV studies have been performed by using cell lines or body fluids, but the number of studies on tissue-derived EVs is still limited. Here, we present a protocol to isolate up to six different EV subpopulations directly from tissues. The approach includes enzymatic treatment of dissociated tissues followed by differential ultracentrifugation and density separation. The isolated EV subpopulations are characterized by electron microscopy and RNA profiling. In addition, their protein cargo can be determined with mass spectrometry, western blot and ExoView. Tissue-EV isolation can be performed in 22 h, but a simplified version can be completed in 8 h. Most experiments with the protocol have used human melanoma metastases, but the protocol can be applied to other cancer and non-cancer tissues. The procedure can be adopted by researchers experienced with cell culture and EV isolation.", "doi": "10.1038/s41596-020-00466-1", "pmid": "33495626", "labels": {"Integrated Microscopy Technologies Gothenburg": "Collaborative", "Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41596-020-00466-1"}], "notes": [], "created": "2023-02-16T08:14:35.630Z", "modified": "2024-01-16T13:46:30.789Z"}, {"entity": "publication", "iuid": "d0790bdca13349e288e63cf5f1aeaa14", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d0790bdca13349e288e63cf5f1aeaa14.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d0790bdca13349e288e63cf5f1aeaa14"}}, "title": "Combined Use of Detergents and Ultrasonication for Generation of an Acellular Pig Larynx.", "authors": [{"family": "Nayakawde", "given": "Nikhil B", "initials": "NB"}, {"family": "Methe", "given": "Ketaki", "initials": "K"}, {"family": "Premaratne", "given": "Goditha U", "initials": "GU"}, {"family": "Banerjee", "given": "Debashish", "initials": "D"}, {"family": "Olausson", "given": "Michael", "initials": "M"}], "type": "journal article", "published": "2021-03-00", "journal": {"title": "Tissue Eng Part A", "issn": "1937-335X", "volume": "27", "issue": "5-6", "pages": "362-371", "issn-l": null}, "abstract": "The larynx is a fairly complex organ comprised of different muscles, cartilages, mucosal membrane, and nerves. Larynx cancer is generally the most common type of head and neck cancer. Treatment options are limited in patients with total or partial laryngectomy. Tissue-engineered organs have shown to be a promising alternative treatment for patients with laryngectomy. In this report we present an alternative and simple procedure to construct a whole pig larynx scaffold consisting of complete acellular structures of integrated muscle and cartilage. Larynges were decellularized (DC) using perfusion-agitation with detergents coupled with ultrasonication. DC larynges were then characterized to investigate the extracellular matrix (ECM) proteins, residual DNA, angiogenic growth factors, and morphological and ultrastructural changes to ECM fibers. After 17 decellularization cycles, no cells were observed in all areas of the larynx as confirmed by hematoxylin and eosin and DAPI (4',6-diamidino-2-phenylindole) staining. However, DC structures of dense thyroid and cricoid cartilage showed remnants of cells. All structures of DC larynges (epiglottis [p < 0.0001], muscle [p < 0.0001], trachea [p = 0.0045], and esophagus [p = 0.0008]) showed DNA <50 ng/mg compared with native larynx. Immunohistochemistry, Masson's trichrome staining, and Luminex analyses showed preservation of important ECM proteins and angiogenic growth factors in DC larynges. Compared with other growth factors, mostly retained growth factors in DC epiglottis, thyroid muscle, and trachea include granulocyte colony-stimulating factor, Leptin, fibroblast growth factor-1, Follistatin, hepatocyte growth factor, and vascular endothelial growth factor-A. Scanning electron microscopy and transmission electron microscopy analysis confirmed the structural arrangements of ECM fibers in larynges to be well preserved after DC. Our findings suggest that larynges can be effectively DC using detergent ultrasonication. ECM proteins and angiogenic growth factors appear to be better preserved using this method when compared with the native structures of larynges. This alternative DC method could be helpful in building scaffolds from dense tissue structures such as cartilage, tendon, larynx, or trachea for future in vitro recellularization studies or in vivo implantation studies in the clinic.", "doi": "10.1089/ten.TEA.2020.0054", "pmid": "32723005", "labels": {"Integrated Microscopy Technologies Gothenburg": "Collaborative"}, "xrefs": [], "notes": [], "created": "2023-02-16T08:20:20.417Z", "modified": "2023-02-16T08:20:20.420Z"}, {"entity": "publication", "iuid": "c719331cfa39445caac67f21fcf18807", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c719331cfa39445caac67f21fcf18807.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c719331cfa39445caac67f21fcf18807"}}, "title": "IL-22 promotes the formation of a MUC17 glycocalyx barrier in the postnatal small intestine during weaning.", "authors": [{"family": "Layunta", "given": "Elena", "initials": "E"}, {"family": "J\u00e4verfelt", "given": "Sofia", "initials": "S"}, {"family": "Dolan", "given": "Brendan", "initials": "B"}, {"family": "Arike", "given": "Liisa", "initials": "L"}, {"family": "Pelaseyed", "given": "Thaher", "initials": "T"}], "type": "journal article", "published": "2021-02-16", "journal": {"title": "Cell Rep", "issn": "2211-1247", "volume": "34", "issue": "7", "pages": "108757", "issn-l": null}, "abstract": "The intestine is under constant exposure to chemicals, antigens, and microorganisms from the external environment. Apical aspects of transporting epithelial cells (enterocytes) form a brush-border membrane (BBM), shaped by packed microvilli coated with a dense glycocalyx. We present evidence showing that the glycocalyx forms an epithelial barrier that prevents exogenous molecules and live bacteria from gaining access to BBM. We use a multi-omics approach to investigate the function and regulation of membrane mucins exposed on the BBM during postnatal development of the mouse small intestine. Muc17 is identified as a major membrane mucin in the glycocalyx that is specifically upregulated by IL-22 as part of an epithelial defense repertoire during weaning. High levels of IL-22 at time of weaning reprogram neonatal postmitotic progenitor enterocytes to differentiate into Muc17-expressing enterocytes, as found in the adult intestine during homeostasis. Our findings propose a role for Muc17 in epithelial barrier function in the small intestine.", "doi": "10.1016/j.celrep.2021.108757", "pmid": "33596425", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S2211-1247(21)00070-X"}], "notes": [], "created": "2023-02-16T08:18:32.334Z", "modified": "2023-02-16T08:18:32.350Z"}, {"entity": "publication", "iuid": "e2f399aac3f9419aa1e2ba0ee63f0215", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e2f399aac3f9419aa1e2ba0ee63f0215.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e2f399aac3f9419aa1e2ba0ee63f0215"}}, "title": "Functional and Neurochemical Identification of Ghrelin Receptor (GHSR)-Expressing Cells of the Lateral Parabrachial Nucleus in Mice.", "authors": [{"family": "Le May", "given": "Marie V", "initials": "MV"}, {"family": "Peris-Sampedro", "given": "Fiona", "initials": "F"}, {"family": "Stoltenborg", "given": "Iris", "initials": "I"}, {"family": "Sch\u00e9le", "given": "Erik", "initials": "E"}, {"family": "Bake", "given": "Tina", "initials": "T"}, {"family": "Adan", "given": "Roger A H", "initials": "RAH"}, {"family": "Dickson", "given": "Suzanne L", "initials": "SL"}], "type": "journal article", "published": "2021-02-15", "journal": {"title": "Front. Neurosci.", "issn": "1662-4548", "volume": "15", "pages": "633018", "issn-l": "1662-453X"}, "abstract": "The lateral parabrachial nucleus (lPBN), located in the pons, is a well-recognized anorexigenic center harboring, amongst others, the calcitonin gene-related peptide (CGRP)-expressing neurons that play a key role. The receptor for the orexigenic hormone ghrelin (the growth hormone secretagogue receptor, GHSR) is also abundantly expressed in the lPBN and ghrelin delivery to this site has recently been shown to increase food intake and alter food choice. Here we sought to explore whether GHSR-expressing cells in the lPBN (GHSR cells) contribute to feeding control, food choice and body weight gain in mice offered an obesogenic diet, involving studies in which GHSR lPBN cells were silenced. We also explored the neurochemical identity of GHSR lPBN cells. To silence GHSR lPBN cells, lPBNGhsr-IRES-Cre male mice were bilaterally injected intra-lPBN with a Cre-dependent viral vector expressing tetanus toxin-light chain. Unlike control wild-type littermates that significantly increased in body weight on the obesogenic diet (i.e., high-fat high-sugar free choice diet comprising chow, lard and 9% sucrose solution), the heterozygous mice with silenced GHSR cells were resistant to diet-induced weight gain with significantly lower food intake and fat weight. The lean phenotype appeared to result from a decreased food intake compared to controls and caloric efficiency was unaltered. Additionally, silencing the GHSR lPBN cells altered food choice, significantly reducing palatable food consumption. RNAscope and immunohistochemical studies of the lPBN revealed considerable co-expression of GHSR with glutamate and pituitary adenylate cyclase-activating peptide (PACAP), and much less with neurotensin, substance P and CGRP. Thus, the GHSR lPBN cells are important for diet-induced weight gain and adiposity, as well as in the regulation of food intake and food choice. Most GHSR lPBN cells were found to be glutamatergic and the majority (76%) do not belong to the well-characterized anorexigenic CGRP cell population.lPBN", "doi": "10.3389/fnins.2021.633018", "pmid": "33658910", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7917048"}], "notes": [], "created": "2023-02-16T08:18:47.492Z", "modified": "2023-02-16T08:18:47.495Z"}, {"entity": "publication", "iuid": "95d1a73cb56f4a2b9861c9617284d756", "links": {"self": {"href": "https://publications.scilifelab.se/publication/95d1a73cb56f4a2b9861c9617284d756.json"}, "display": {"href": "https://publications.scilifelab.se/publication/95d1a73cb56f4a2b9861c9617284d756"}}, "title": "Circulating tight-junction proteins are potential biomarkers for blood-brain barrier function in a model of neonatal hypoxic/ischemic brain injury.", "authors": [{"family": "Andersson", "given": "E Axel", "initials": "EA", "orcid": "0000-0002-7165-3709", "researcher": {"href": "https://publications.scilifelab.se/researcher/a6e13e46b3af48ea8cea3f571abdb567.json"}}, {"family": "Mallard", "given": "Carina", "initials": "C"}, {"family": "Ek", "given": "C Joakim", "initials": "CJ"}], "type": "journal article", "published": "2021-02-10", "journal": {"title": "Fluids Barriers CNS", "issn": "2045-8118", "volume": "18", "issue": "1", "pages": "7", "issn-l": null}, "abstract": "Neonatal encephalopathy often leads to lifelong disabilities with limited treatments currently available. The brain vasculature is an important factor in many neonatal neurological disorders but there is a lack of diagnostic tools to evaluate the brain vascular dysfunction of neonates in the clinical setting. Measurement of blood-brain barrier tight-junction (TJ) proteins have shown promise as biomarkers for brain injury in the adult. Here we tested the biomarker potential of tight-junctions in the context of neonatal brain injury.\n\nThe levels of TJ-proteins (occluding, claudin-5, and zonula occludens protein 1) in both blood plasma and cerebrospinal fluid (CSF) as well as blood-brain barrier function via 14C-sucrose (342 Da) and Evans blue extravasation were measured in a hypoxia/ischemia brain-injury model in neonatal rats.\n\nTime-dependent changes of occludin and claudin-5 levels could be measured in blood and CSF after hypoxia/ischemia with males generally having higher levels than females. The levels of claudin-5 in CSF correlated with the severity of the brain injury at 24 h post- hypoxia/ischemia. Simultaneously, we detected early increase in blood-brain barrier-permeability at 6 and 24 h after hypoxia/ischemia.\n\nLevels of circulating claudin-5 and occludin are increased after hypoxic/ischemic brain injuries and blood-brain barrier-impairment and have promise as early biomarkers for cerebral vascular dysfunction and as a tool for risk assessment of neonatal brain injuries.", "doi": "10.1186/s12987-021-00240-9", "pmid": "33568200", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7877092"}, {"db": "pii", "key": "10.1186/s12987-021-00240-9"}], "notes": [], "created": "2023-02-16T08:14:02.423Z", "modified": "2023-02-16T08:14:02.493Z"}, {"entity": "publication", "iuid": "97cafc652acb4df18133e688497b7a9e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/97cafc652acb4df18133e688497b7a9e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/97cafc652acb4df18133e688497b7a9e"}}, "title": "CD8+ T cells in the central nervous system of mice with herpes simplex infection are highly activated and express high levels of CCR5 and CXCR3.", "authors": [{"family": "Lind", "given": "Liza", "initials": "L"}, {"family": "Svensson", "given": "Alexandra", "initials": "A"}, {"family": "Th\u00f6rn", "given": "Karolina", "initials": "K"}, {"family": "Krzyzowska", "given": "Malgorzata", "initials": "M"}, {"family": "Eriksson", "given": "Kristina", "initials": "K"}], "type": "journal article", "published": "2021-02-00", "journal": {"title": "J Neurovirol", "issn": "1538-2443", "volume": "27", "issue": "1", "pages": "145-153", "issn-l": null}, "abstract": "Herpes simplex virus type 2 (HSV-2) is a neurotropic virus that can cause meningitis, an inflammation of the meninges in the central nervous system. T cells are key players in viral clearance, and these cells migrate from peripheral blood into the central nervous system upon infection. Several factors contribute to T cell migration, including the expression of chemokines in the inflamed tissue that attract T cells through their expression of chemokine receptors. Here we investigated CD8+ T cell profile in the spinal cord in a mouse model of herpes simplex virus type 2 neuroinflammation. Mice were infected with HSV-2 and sacrificed when showing signs of neuroinflammation. Cells and/or tissue from spinal cord, spleen, and blood were analyzed for expression of activation markers, chemokine receptors, and chemokines. High numbers of CD8+ T cells were present in the spinal cord following genital HSV-2-infection. CD8+ T cells were highly activated and HSV-2 glycoprotein B -specific effector cells, some of which showed signs of recent degranulation. They also expressed high levels of many chemokine receptors, in particular CCR2, CCR4, CCR5, and CXCR3. Investigating corresponding receptor ligands in spinal cord tissue revealed markedly increased expression of the cognate ligands CCL2, CCL5, CCL8, CCL12, and CXCL10. This study shows that during herpesvirus neuroinflammation anti-viral CD8+ T cells accumulate in the CNS. CD8+ T cells in the CNS also express chemotactic receptors cognate to the chemotactic gradients in the spinal cord. This indicates that anti-viral CD8+ T cells may migrate to infected areas in the spinal cord during herpesvirus neuroinflammation in response to chemotactic gradients.", "doi": "10.1007/s13365-020-00940-2", "pmid": "33492607", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7831625"}, {"db": "pii", "key": "10.1007/s13365-020-00940-2"}], "notes": [], "created": "2023-02-16T08:19:01.696Z", "modified": "2023-02-16T08:19:01.739Z"}, {"entity": "publication", "iuid": "d3777afc02b2443aa6be5785553e91a5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d3777afc02b2443aa6be5785553e91a5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d3777afc02b2443aa6be5785553e91a5"}}, "title": "SMAD4 haploinsufficiency in small intestinal neuroendocrine tumors.", "authors": [{"family": "Hofving", "given": "Tobias", "initials": "T"}, {"family": "Elias", "given": "Erik", "initials": "E"}, {"family": "Rehammar", "given": "Anna", "initials": "A"}, {"family": "Inge", "given": "Linda", "initials": "L"}, {"family": "Altiparmak", "given": "G\u00fclay", "initials": "G"}, {"family": "Persson", "given": "Marta", "initials": "M"}, {"family": "Kristiansson", "given": "Erik", "initials": "E"}, {"family": "Johansson", "given": "Martin E", "initials": "ME"}, {"family": "Nilsson", "given": "Ola", "initials": "O"}, {"family": "Arvidsson", "given": "Yvonne", "initials": "Y", "orcid": "0000-0002-9599-3791", "researcher": {"href": "https://publications.scilifelab.se/researcher/d3cca2ea2e5d4ef78c6a9beaf517bbc5.json"}}], "type": "journal article", "published": "2021-01-28", "journal": {"title": "BMC Cancer", "issn": "1471-2407", "volume": "21", "issue": "1", "pages": "101", "issn-l": "1471-2407"}, "abstract": "Patients with small intestinal neuroendocrine tumors (SINETs) frequently present with lymph node and liver metastases at the time of diagnosis, but the molecular changes that lead to the progression of these tumors are largely unknown. Sequencing studies have only identified recurrent point mutations at low frequencies with CDKN1B being the most common harboring heterozygous mutations in less than 10% of all tumors. Although SINETs are genetically stable tumors with a low frequency of point mutations and indels, they often harbor recurrent hemizygous copy number alterations (CNAs) yet the functional implications of these CNA are unclear.\n\nUtilizing comparative genomic hybridization (CGH) arrays we analyzed the CNA profile of 131 SINETs from 117 patients. Two tumor suppressor genes and corresponding proteins i.e. SMAD4, and CDKN1B, were further characterized using a tissue microarray (TMA) with 846 SINETs. Immunohistochemistry (IHC) was used to quantify protein expression in TMA samples and this was correlated with chromosome number evaluated with fluorescent in-situ hybridization (FISH). Intestinal tissue from a Smad4+/- mouse model was used to detect entero-endocrine cell hyperplasia with IHC.\n\nAnalyzing the CGH arrays we found loss of chromosome 18q and SMAD4 in 71% of SINETs and that focal loss of chromosome 12 affecting the CDKN1B was present in 9.4% of SINETs. No homozygous loss of chromosome 18 was detected. Hemizygous loss of SMAD4, but not CDKN1B, significantly correlated with reduced protein levels but hemizygous loss of SMAD4 did not induce entero-endocrine cell hyperplasia in the Smad4+/- mouse model. In addition, patients with low SMAD4 protein expression in primary tumors more often presented with metastatic disease.\n\nHemizygous loss of chromosome 18q and the SMAD4 gene is the most common genetic event in SINETs and our results suggests that this could influence SMAD4 protein expression and spread of metastases. Although SMAD4 haploinsufficiency alone did not induce tumor initiation, loss of chromosome 18 could represent an evolutionary advantage in SINETs explaining the high prevalence of this aberration. Functional consequences of reduced SMAD4 protein levels could hypothetically be a potential mechanism as to why loss of chromosome 18 appears to be clonally selected in SINETs.", "doi": "10.1186/s12885-021-07786-9", "pmid": "33509126", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7841913"}, {"db": "pii", "key": "10.1186/s12885-021-07786-9"}], "notes": [], "created": "2023-02-16T08:17:10.434Z", "modified": "2023-02-16T08:17:10.476Z"}, {"entity": "publication", "iuid": "b8f68cd4f7364dfb9f73fd59a1262fcc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b8f68cd4f7364dfb9f73fd59a1262fcc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b8f68cd4f7364dfb9f73fd59a1262fcc"}}, "title": "Correlated fluorescence microscopy and multi-ion beam secondary ion mass spectrometry imaging reveals phosphatidylethanolamine increases in the membrane of cancer cells over-expressing the molecular chaperone subunit CCT\u03b4.", "authors": [{"family": "Fletcher", "given": "John S", "initials": "JS"}, {"family": "S\u00e4mfors", "given": "Sanna", "initials": "S"}, {"family": "Vallin", "given": "Josefine", "initials": "J"}, {"family": "Svanstr\u00f6m", "given": "Andreas", "initials": "A"}, {"family": "Grantham", "given": "Julie", "initials": "J"}], "type": "journal article", "published": "2021-01-00", "journal": {"title": "Anal Bioanal Chem", "issn": "1618-2650", "volume": "413", "issue": "2", "pages": "445-453", "issn-l": "1618-2642"}, "abstract": "Changes in the membrane composition of sub-populations of cells can influence different properties with importance to tumour growth, metastasis and treatment efficacy. In this study, we use correlated fluorescence microscopy and ToF-SIMS with C60+ and (CO2)6k+ ion beams to identify and characterise sub-populations of cells based on successful transfection leading to over-expression of CCT\u03b4, a component of the multi-subunit molecular chaperone named chaperonin-containing tailless complex polypeptide 1 (CCT). CCT has been linked to increased cell growth and proliferation and is known to affect cell morphology but corresponding changes in lipid composition of the membrane have not been measured until now. Multivariate analysis of the surface mass spectra from single cells, focused on the intact lipid ions, indicates an enrichment of phosphatidylethanolamine species in the transfected cells. While the lipid changes in this case are driven by the structural changes in the protein cytoskeleton, the consequence of phosphatidylethanolamine enrichment may have additional implications in cancer such as increased membrane fluidity, increased motility and an ability to adapt to a depletion of unsaturated lipids during cancer cell proliferation. This study demonstrates a successful fluorescence microscopy-guided cell by cell membrane lipid analysis with broad application to biological investigation.Graphical abstract.", "doi": "10.1007/s00216-020-03013-9", "pmid": "33130974", "labels": {"Integrated Microscopy Technologies Gothenburg": "Technology development"}, "xrefs": [{"db": "pmc", "key": "PMC7806562"}, {"db": "pii", "key": "10.1007/s00216-020-03013-9"}], "notes": [], "created": "2023-02-16T08:16:39.503Z", "modified": "2023-02-16T08:16:39.506Z"}, {"entity": "publication", "iuid": "976e52a6a98747bfa09f48511cc06e09", "links": {"self": {"href": "https://publications.scilifelab.se/publication/976e52a6a98747bfa09f48511cc06e09.json"}, "display": {"href": "https://publications.scilifelab.se/publication/976e52a6a98747bfa09f48511cc06e09"}}, "title": "Depletion of protein kinase STK25 ameliorates renal lipotoxicity and protects against diabetic kidney disease.", "authors": [{"family": "Cansby", "given": "Emmelie", "initials": "E"}, {"family": "Caputo", "given": "Mara", "initials": "M"}, {"family": "Gao", "given": "Lei", "initials": "L"}, {"family": "Kulkarni", "given": "Nagaraj M", "initials": "NM"}, {"family": "Nerstedt", "given": "Annika", "initials": "A"}, {"family": "St\u00e5hlman", "given": "Marcus", "initials": "M"}, {"family": "Bor\u00e9n", "given": "Jan", "initials": "J"}, {"family": "Porosk", "given": "Rando", "initials": "R"}, {"family": "Soomets", "given": "Ursel", "initials": "U"}, {"family": "Pedrelli", "given": "Matteo", "initials": "M"}, {"family": "Parini", "given": "Paolo", "initials": "P"}, {"family": "Marschall", "given": "Hanns-Ulrich", "initials": "HU"}, {"family": "Nystr\u00f6m", "given": "Jenny", "initials": "J"}, {"family": "Howell", "given": "Brian W", "initials": "BW"}, {"family": "Mahlapuu", "given": "Margit", "initials": "M"}], "type": "journal article", "published": "2020-12-17", "journal": {"title": "JCI Insight", "issn": "2379-3708", "volume": "5", "issue": "24", "issn-l": "2379-3708"}, "abstract": "Diabetic kidney disease (DKD) is the most common cause of severe renal disease worldwide and the single strongest predictor of mortality in diabetes patients. Kidney steatosis has emerged as a critical trigger in the pathogenesis of DKD; however, the molecular mechanism of renal lipotoxicity remains largely unknown. Our recent studies in genetic mouse models, human cell lines, and well-characterized patient cohorts have identified serine/threonine protein kinase 25 (STK25) as a critical regulator of ectopic lipid storage in several metabolic organs prone to diabetic damage. Here, we demonstrate that overexpression of STK25 aggravates renal lipid accumulation and exacerbates structural and functional kidney injury in a mouse model of DKD. Reciprocally, inhibiting STK25 signaling in mice ameliorates diet-induced renal steatosis and alleviates the development of DKD-associated pathologies. Furthermore, we find that STK25 silencing in human kidney cells protects against lipid deposition, as well as oxidative and endoplasmic reticulum stress. Together, our results suggest that STK25 regulates a critical node governing susceptibility to renal lipotoxicity and that STK25 antagonism could mitigate DKD progression.", "doi": "10.1172/jci.insight.140483", "pmid": "33170807", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7819747"}, {"db": "pii", "key": "140483"}], "notes": [], "created": "2023-02-16T08:05:50.037Z", "modified": "2023-02-16T08:05:50.051Z"}, {"entity": "publication", "iuid": "c6ac69c76dae4296b4cfe9afc374fcaf", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c6ac69c76dae4296b4cfe9afc374fcaf.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c6ac69c76dae4296b4cfe9afc374fcaf"}}, "title": "A Model of Germinal Matrix Hemorrhage in Preterm Rat Pups.", "authors": [{"family": "Jinnai", "given": "Masako", "initials": "M"}, {"family": "Koning", "given": "Gabriella", "initials": "G"}, {"family": "Singh-Mallah", "given": "Gagandeep", "initials": "G"}, {"family": "Jonsdotter", "given": "Andrea", "initials": "A"}, {"family": "Leverin", "given": "Anna-Lena", "initials": "AL"}, {"family": "Svedin", "given": "Pernilla", "initials": "P"}, {"family": "Nair", "given": "Syam", "initials": "S"}, {"family": "Takeda", "given": "Satoru", "initials": "S"}, {"family": "Wang", "given": "Xiaoyang", "initials": "X"}, {"family": "Mallard", "given": "Carina", "initials": "C"}, {"family": "Ek", "given": "Carl Joakim", "initials": "CJ"}, {"family": "Rocha-Ferreira", "given": "Eridan", "initials": "E"}, {"family": "Hagberg", "given": "Henrik", "initials": "H"}], "type": "journal article", "published": "2020-12-03", "journal": {"title": "Front Cell Neurosci", "issn": "1662-5102", "volume": "14", "pages": "535320", "issn-l": "1662-5102"}, "abstract": "Germinal matrix hemorrhage (GMH) is a serious complication in extremely preterm infants associated with neurological deficits and mortality. The purpose of the present study was to develop and characterize a grade III and IV GMH model in postnatal day 5 (P5) rats, the equivalent of preterm human brain maturation. P5 Wistar rats were exposed to unilateral GMH through intracranial injection into the striatum close to the germinal matrix with 0.1, 0.2, or 0.3 U of collagenase VII. During 10 days following GMH induction, motor functions and body weight were assessed and brain tissue collected at P16. Animals were tested for anxiety, motor coordination and motor asymmetry on P22-26 and P36-40. Using immunohistochemical staining and neuropathological scoring we found that a collagenase dose of 0.3 U induced GMH. Neuropathological assessment revealed that the brain injury in the collagenase group was characterized by dilation of the ipsilateral ventricle combined with mild to severe cellular necrosis as well as mild to moderate atrophy at the levels of striatum and subcortical white matter, and to a lesser extent, hippocampus and cortex. Within 0.5 h post-collagenase injection there was clear bleeding at the site of injury, with progressive increase in iron and infiltration of neutrophils in the first 24 h, together with focal microglia activation. By P16, blood was no longer observed, although significant gray and white matter brain infarction persisted. Astrogliosis was also detected at this time-point. Animals exposed to GMH performed worse than controls in the negative geotaxis test and also opened their eyes with latency compared to control animals. At P40, GMH rats spent more time in the center of open field box and moved at higher speed compared to the controls, and continued to show ipsilateral injury in striatum and subcortical white matter. We have established a P5 rat model of collagenase-induced GMH for the study of preterm brain injury. Our results show that P5 rat pups exposed to GMH develop moderate brain injury affecting both gray and white matter associated with delayed eye opening and abnormal motor functions. These animals develop hyperactivity and show reduced anxiety in the juvenile stage.", "doi": "10.3389/fncel.2020.535320", "pmid": "33343300", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7744792"}], "notes": [], "created": "2023-02-16T08:07:43.072Z", "modified": "2023-02-16T08:07:43.092Z"}, {"entity": "publication", "iuid": "794a7c23da0549009ddf423b8184e00c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/794a7c23da0549009ddf423b8184e00c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/794a7c23da0549009ddf423b8184e00c"}}, "title": "Glycocholic acid and butyrate synergistically increase vitamin D-induced calcium uptake in Caco-2 intestinal epithelial cell monolayers.", "authors": [{"family": "Casselbrant", "given": "Anna", "initials": "A"}, {"family": "F\u00e4ndriks", "given": "Lars", "initials": "L"}, {"family": "Wallenius", "given": "Ville", "initials": "V"}], "type": "journal article", "published": "2020-12-00", "journal": {"title": "Bone Rep", "issn": "2352-1872", "volume": "13", "pages": "100294", "issn-l": null}, "abstract": "Roux-en-Y gastric bypass (RYGB) substantially decreases intestinal calcium absorption and may eventually lead to bone resorption. This is likely a consequence of bile diversion from the alimentary limb, as the presence of bile seems necessary for vitamin D-mediated calcium uptake. We recently suggested that the mediating mechanism may be a down-regulation of the vitamin D co-activator heat-shock protein (Hsp)90\u03b2. Recent evidence suggests that vitamin D may have effects on both active and passive calcium absorption.\n\nTo identify mechanisms in vitro that may be responsible for the decreased calcium absorption after RYGB. We hypothesized that bile, alone or in concert with nutritional compounds, could be of importance.\n\nCaco-2 cells were grown confluent on semi-permeable membranes in a double-chamber setup to mimic small intestinal mucosa. The effect of bile acids chenodeoxycholic, lithocholic, glycocholic and taurocholic acid, with and without the addition of the fatty-acid butyrate, were tested for their effects on Hsp90\u03b2 expression and active and passive calcium-flux monitored using radioactive 45Ca.\n\nWe initially found that whole human bile, but only together with the fatty acid butyrate, potently induced Hsp90\u03b2 expression. In line with this, a single bile acid, e.g. glycocholic acid (GCA), in combination with butyrate, increased Hsp90\u03b2 expression (40 \u00b1 13% vs. GCA, butyrate or vehicle alone; p < 0,001; n = 14-25). Further, this combination together with vitamin D increased the passive gradient-driven flux of calcium, compared to stimulation with vitamin D alone or in combination with either GCA or butyrate (880 \u00b1 217% vs. vitamin D and GCA or butyrate, or vitamin D only; p = 0,01-0.006; n = 5-11). Surprisingly, this combination had no effect on active calcium transport in the absence of calcium gradient.\n\nThe combination of GCA and butyrate increased gradient-driven calcium uptake up to 9-fold in Caco-2 intestinal epithelial cells, but had no effect on active calcium absorption. This effect was mediated via the vitamin D receptor co-activator Hsp90\u03b2.", "doi": "10.1016/j.bonr.2020.100294", "pmid": "32715032", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7371747"}, {"db": "pii", "key": "S2352-1872(20)30054-1"}], "notes": [], "created": "2023-02-16T08:05:39.517Z", "modified": "2023-02-16T08:05:39.519Z"}, {"entity": "publication", "iuid": "846d39f0d96e40b9b583e4a5b0420bef", "links": {"self": {"href": "https://publications.scilifelab.se/publication/846d39f0d96e40b9b583e4a5b0420bef.json"}, "display": {"href": "https://publications.scilifelab.se/publication/846d39f0d96e40b9b583e4a5b0420bef"}}, "title": "Obesity-associated microbiota contributes to mucus layer defects in genetically obese mice.", "authors": [{"family": "Schroeder", "given": "Bjoern O", "initials": "BO"}, {"family": "Birchenough", "given": "George M H", "initials": "GMH"}, {"family": "Pradhan", "given": "Meenakshi", "initials": "M"}, {"family": "Nystr\u00f6m", "given": "Elisabeth E L", "initials": "EEL"}, {"family": "Henricsson", "given": "Marcus", "initials": "M"}, {"family": "Hansson", "given": "Gunnar C", "initials": "GC"}, {"family": "B\u00e4ckhed", "given": "Fredrik", "initials": "F"}], "type": "journal article", "published": "2020-11-13", "journal": {"title": "J. Biol. Chem.", "issn": "1083-351X", "volume": "295", "issue": "46", "pages": "15712-15726", "issn-l": "0021-9258"}, "abstract": "The intestinal mucus layer is a physical barrier separating the tremendous number of gut bacteria from the host epithelium. Defects in the mucus layer have been linked to metabolic diseases, but previous studies predominantly investigated mucus function during high-caloric/low-fiber dietary interventions, thus making it difficult to separate effects mediated directly through diet quality from potential obesity-dependent effects. As such, we decided to examine mucus function in mouse models with metabolic disease to distinguish these factors. Here we show that, in contrast to their lean littermates, genetically obese (ob/ob) mice have a defective inner colonic mucus layer that is characterized by increased penetrability and a reduced mucus growth rate. Exploiting the coprophagic behavior of mice, we next co-housed ob/ob and lean mice to investigate if the gut microbiota contributed to these phenotypes. Co-housing rescued the defect of the mucus growth rate, whereas mucus penetrability displayed an intermediate phenotype in both mouse groups. Of note, non-obese diabetic mice with high blood glucose levels displayed a healthy colonic mucus barrier, indicating that the mucus defect is obesity- rather than glucose-mediated. Thus, our data suggest that the gut microbiota community of obesity-prone mice may regulate obesity-associated defects in the colonic mucosal barrier, even in the presence of dietary fiber.", "doi": "10.1074/jbc.RA120.015771", "pmid": "32900852", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7667970"}, {"db": "pii", "key": "S0021-9258(17)50399-3"}], "notes": [], "created": "2023-02-16T08:09:48.007Z", "modified": "2023-02-16T08:09:48.009Z"}, {"entity": "publication", "iuid": "7996780e07c04e949fd225c2a80edf09", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7996780e07c04e949fd225c2a80edf09.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7996780e07c04e949fd225c2a80edf09"}}, "title": "ENPL-1, the Caenorhabditis elegans homolog of GRP94, promotes insulin secretion via regulation of proinsulin processing and maturation.", "authors": [{"family": "Podraza-Farhanieh", "given": "Agnieszka", "initials": "A", "orcid": "0000-0002-1120-8216", "researcher": {"href": "https://publications.scilifelab.se/researcher/8244c5dad7974bc0a2a4ec38cc3e58ce.json"}}, {"family": "Natarajan", "given": "Balasubramanian", "initials": "B", "orcid": "0000-0003-2371-0550", "researcher": {"href": "https://publications.scilifelab.se/researcher/3ca28d7e37654cd0a4b497d7a0d72b4e.json"}}, {"family": "Raj", "given": "Dorota", "initials": "D", "orcid": "0000-0002-7357-2902", "researcher": {"href": "https://publications.scilifelab.se/researcher/23ff7c388c2b43e3a9d3a3514fe5e049.json"}}, {"family": "Kao", "given": "Gautam", "initials": "G", "orcid": "0000-0003-1313-3024", "researcher": {"href": "https://publications.scilifelab.se/researcher/4575b678a90740428136c9f5e1bdd53b.json"}}, {"family": "Naredi", "given": "Peter", "initials": "P", "orcid": "0000-0002-5652-0422", "researcher": {"href": "https://publications.scilifelab.se/researcher/a41ccd84008a4a94a29410451bc012c9.json"}}], "type": "journal article", "published": "2020-10-27", "journal": {"title": "Development", "issn": "1477-9129", "volume": "147", "issue": "20", "issn-l": "0950-1991"}, "abstract": "Insulin/IGF signaling in Caenorhabditis elegans is crucial for proper development of the dauer larva and growth control. Mutants disturbing insulin processing, secretion and downstream signaling perturb this process and have helped identify genes that affect progression of type 2 diabetes. Insulin maturation is required for its proper secretion by pancreatic \u03b2 cells. The role of the endoplasmic reticulum (ER) chaperones in insulin processing and secretion needs further study. We show that the C. elegans ER chaperone ENPL-1/GRP94 (HSP90B1), acts in dauer development by promoting insulin secretion and signaling. Processing of a proinsulin likely involves binding between the two proteins via a specific domain. We show that, in enpl-1 mutants, an unprocessed insulin exits the ER lumen and is found in dense core vesicles, but is not secreted. The high ER stress in enpl-1 mutants does not cause the secretion defect. Importantly, increased ENPL-1 levels result in increased secretion. Taken together, our work indicates that ENPL-1 operates at the level of insulin availability and is an essential modulator of insulin processing and secretion.", "doi": "10.1242/dev.190082", "pmid": "33037039", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "dev.190082"}], "notes": [], "created": "2023-02-16T08:08:41.919Z", "modified": "2023-02-16T08:08:42.245Z"}, {"entity": "publication", "iuid": "e7e7ddd7c2234dac93697ac7e3483c70", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e7e7ddd7c2234dac93697ac7e3483c70.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e7e7ddd7c2234dac93697ac7e3483c70"}}, "title": "Increased antibiotic efficacy and noninvasive monitoring of Staphylococcus epidermidis biofilms using per-cysteamine-substituted \u03b3-cyclodextrin - A delivery effect validated by fluorescence microscopy.", "authors": [{"family": "Thomsen", "given": "Hanna", "initials": "H"}, {"family": "Agnes", "given": "Marco", "initials": "M"}, {"family": "Uwangue", "given": "Owens", "initials": "O"}, {"family": "Persson", "given": "Linn\u00e9a", "initials": "L"}, {"family": "Mattsson", "given": "Matilda", "initials": "M"}, {"family": "Graf", "given": "Fabrice E", "initials": "FE"}, {"family": "Kasimati", "given": "Eleni-Marina", "initials": "EM"}, {"family": "Yannakopoulou", "given": "Konstantina", "initials": "K"}, {"family": "Ericson", "given": "Marica B", "initials": "MB"}, {"family": "Farewell", "given": "Anne", "initials": "A"}], "type": "journal article", "published": "2020-09-25", "journal": {"title": "Int J Pharm", "issn": "1873-3476", "volume": "587", "pages": "119646", "issn-l": "0378-5173"}, "abstract": "Limited and poor delivery of antibiotics is cited as one reason for the difficulty in treating antibiotic-resistant biofilms associated with chronic infections. We investigate the effectiveness of a positively charged, single isomer cyclodextrin derivative, octakis[6-(2-aminoethylthio)-6-deoxy]-\u03b3-CD (\u03b3Cys) to improve the delivery of antibiotics to biofilms. Using multiphoton laser scanning microscopy complemented with super-resolution fluorescence microscopy, we showed that \u03b3Cys tagged with fluorescein (FITC) is uniformly distributed throughout live S. epidermidis biofilm cultures in vitro and results suggest it is localized extracellularly in the biofilm matrix. NMR spectroscopic data in aqueous solution confirm that \u03b3Cys forms inclusion complexes with both the antibiotics oxacillin and rifampicin. Efficacy of \u03b3Cys/antibiotic (oxacillin and rifampicin) was measured in the biofilms. While treatment with \u03b3Cys/oxacillin had little improvement over oxacillin alone, \u03b3Cys/rifampicin reduced the biofilm viability to background levels demonstrating a remarkable improvement over rifampicin alone. The strong synergistic effect for \u03b3Cys/rifampicin is at this stage not clearly understood, but plausible explanations are related to increased solubility of rifampicin upon complexation and/or synergistic interference with components of the biofilm. The results demonstrate that designed cyclodextrin nanocarriers, like \u03b3Cys, efficiently deliver suitable antibiotics to biofilms and that fluorescence microscopy offers a novel approach for mechanistic investigations.", "doi": "10.1016/j.ijpharm.2020.119646", "pmid": "32679261", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S0378-5173(20)30630-X"}], "notes": [], "created": "2023-02-16T08:10:09.500Z", "modified": "2023-02-16T08:10:09.503Z"}, {"entity": "publication", "iuid": "f5196895ac8a4cebb5143f36ce3b1737", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f5196895ac8a4cebb5143f36ce3b1737.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f5196895ac8a4cebb5143f36ce3b1737"}}, "title": "Toward Two-Photon Absorbing Dyes with Unusually Potentiated Nonlinear Fluorescence Response.", "authors": [{"family": "Benitez-Martin", "given": "Carlos", "initials": "C", "orcid": "0000-0003-1821-9388", "researcher": {"href": "https://publications.scilifelab.se/researcher/d1fcdd6e053b462998fe7f463be60d96.json"}}, {"family": "Li", "given": "Shiming", "initials": "S"}, {"family": "Dominguez-Alfaro", "given": "Antonio", "initials": "A"}, {"family": "Najera", "given": "Francisco", "initials": "F", "orcid": "0000-0002-1635-5514", "researcher": {"href": "https://publications.scilifelab.se/researcher/59a60d855d794d45a9fff4746867037f.json"}}, {"family": "P\u00e9rez-Inestrosa", "given": "Ezequiel", "initials": "E", "orcid": "0000-0001-7546-5273", "researcher": {"href": "https://publications.scilifelab.se/researcher/5ecc62575cbc43d9bfb86efd8299499c.json"}}, {"family": "Pischel", "given": "Uwe", "initials": "U", "orcid": "0000-0001-8893-9829", "researcher": {"href": "https://publications.scilifelab.se/researcher/f834b537191b46659d27846e05238ef3.json"}}, {"family": "Andr\u00e9asson", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4695-7943", "researcher": {"href": "https://publications.scilifelab.se/researcher/28eb5affb5664c54be9171dfce6bea15.json"}}], "type": "journal article", "published": "2020-09-02", "journal": {"title": "J. Am. Chem. Soc.", "issn": "1520-5126", "volume": "142", "issue": "35", "pages": "14854-14858", "issn-l": "0002-7863"}, "abstract": "The combination of two two-photon-induced processes in a F\u00f6rster resonance energy transfer (FRET)-operated photochromic fluorene-dithienylethene dyad lays the foundation for the observation of a quartic dependence of the fluorescence signal on the excitation light intensity. While this photophysical behavior is predicted for a four-photon absorbing dye, the herein proposed approach opens the way to use two-photon absorbing dyes, reaching the same performance. Hence, the spatial resolution limit, being a critical parameter for applications in fluorescence imaging or data storage with common two-photon absorbing dyes, is dramatically improved.", "doi": "10.1021/jacs.0c07377", "pmid": "32799520", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7498150"}], "notes": [], "created": "2023-02-16T08:04:03.866Z", "modified": "2023-02-16T08:04:04.030Z"}, {"entity": "publication", "iuid": "82661edac9d74b09b7e33a0ef24eaae1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/82661edac9d74b09b7e33a0ef24eaae1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/82661edac9d74b09b7e33a0ef24eaae1"}}, "title": "Hyperandrogenism and insulin resistance modulate gravid uterine and placental ferroptosis in PCOS-like rats.", "authors": [{"family": "Zhang", "given": "Yuehui", "initials": "Y"}, {"family": "Hu", "given": "Min", "initials": "M"}, {"family": "Jia", "given": "Wenyan", "initials": "W"}, {"family": "Liu", "given": "Guoqi", "initials": "G"}, {"family": "Zhang", "given": "Jiao", "initials": "J"}, {"family": "Wang", "given": "Bing", "initials": "B"}, {"family": "Li", "given": "Juan", "initials": "J"}, {"family": "Cui", "given": "Peng", "initials": "P"}, {"family": "Li", "given": "Xin", "initials": "X"}, {"family": "Lager", "given": "Susanne", "initials": "S"}, {"family": "Sferruzzi-Perri", "given": "Amanda Nancy", "initials": "AN"}, {"family": "Han", "given": "Yanhua", "initials": "Y"}, {"family": "Liu", "given": "Songjiang", "initials": "S"}, {"family": "Wu", "given": "Xiaoke", "initials": "X"}, {"family": "Br\u00e4nnstr\u00f6m", "given": "Mats", "initials": "M"}, {"family": "Shao", "given": "Linus R", "initials": "LR"}, {"family": "Billig", "given": "H\u00e5kan", "initials": "H"}], "type": "journal article", "published": "2020-09-00", "journal": {"title": "J Endocrinol", "issn": "1479-6805", "volume": "246", "issue": "3", "pages": "247-263", "issn-l": null}, "abstract": "Women with polycystic ovary syndrome (PCOS) have hyperandrogenism and insulin resistance and a high risk of miscarriage during pregnancy. Similarly, in rats, maternal exposure to 5\u03b1-dihydrotestosterone (DHT) and insulin from gestational day 7.5 to 13.5 leads to hyperandrogenism and insulin resistance and subsequently increased fetal loss. A variety of hormonal and metabolic stimuli are able to trigger different types of regulated cell death under physiological and pathological conditions. These include ferroptosis, apoptosis and necroptosis. We hypothesized that, in rats, maternal hyperandrogenism and insulin-resistance-induced fetal loss is mediated, at least in part, by changes in the ferroptosis, apoptosis and necroptosis pathways in the gravid uterus and placenta. Compared with controls, we found that co-exposure to DHT and insulin led to decreased levels of glutathione peroxidase 4 (GPX4) and glutathione, increased glutathione + glutathione disulfide and malondialdehyde, aberrant expression of ferroptosis-associated genes (Acsl4, Tfrc, Slc7a11, and Gclc), increased iron deposition and activated ERK/p38/JNK phosphorylation in the gravid uterus. In addition, we observed shrunken mitochondria with electron-dense cristae, which are key features of ferroptosis-related mitochondrial morphology, as well as increased expression of Dpp4, a mitochondria-encoded gene responsible for ferroptosis induction in the uteri of rats co-exposed to DHT and insulin. However, in the placenta, DHT and insulin exposure only partially altered the expression of ferroptosis-related markers (e.g. region-dependent GPX4, glutathione + glutathione disulfide, malondialdehyde, Gls2 and Slc7a11 mRNAs, and phosphorylated p38 levels). Moreover, we found decreased expression of Dpp4 mRNA and increased expression of Cisd1 mRNA in placentas of rats co-exposed to DHT and insulin. Further, DHT + insulin-exposed pregnant rats exhibited decreased apoptosis in the uterus and increased necroptosis in the placenta. Our findings suggest that maternal hyperandrogenism and insulin resistance causes the activation of ferroptosis in the gravid uterus and placenta, although this is mediated via different mechanisms operating at the molecular and cellular levels. Our data also suggest that apoptosis and necroptosis may play a role in coordinating or compensating for hyperandrogenism and insulin-resistance-induced ferroptosis when the gravid uterus and placenta are dysfunctional.", "doi": "10.1530/JOE-20-0155", "pmid": "32590339", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "JOE-20-0155"}], "notes": [], "created": "2023-02-16T08:10:35.403Z", "modified": "2023-02-16T08:13:23.023Z"}, {"entity": "publication", "iuid": "a4b22326ad624507868b05ce1ce81449", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a4b22326ad624507868b05ce1ce81449.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a4b22326ad624507868b05ce1ce81449"}}, "title": "Bulk-Processed Pd Nanocube\u2013Poly(methyl methacrylate) Nanocomposites as Plasmonic Plastics for Hydrogen Sensing", "authors": [{"family": "Darmadi", "given": "Iwan", "initials": "I", "orcid": "0000-0002-5921-9336", "researcher": {"href": "https://publications.scilifelab.se/researcher/d24542fa29854812a58bc1906bdeaf8a.json"}}, {"family": "Stola\u015b", "given": "Alicja", "initials": "A", "orcid": "0000-0002-6736-9553", "researcher": {"href": "https://publications.scilifelab.se/researcher/f882b7702b204bc88c1e7a81b9554194.json"}}, {"family": "\u00d6stergren", "given": "Ida", "initials": "I"}, {"family": "Berke", "given": "Barbara", "initials": "B", "orcid": "0000-0002-3105-2036", "researcher": {"href": "https://publications.scilifelab.se/researcher/b7e866bd004143959951261606413e8f.json"}}, {"family": "Nugroho", "given": "Ferry Anggoro Ardy", "initials": "FAA", "orcid": "0000-0001-5571-0454", "researcher": {"href": "https://publications.scilifelab.se/researcher/199aa547e4154722a89bd54cb072b3d4.json"}}, {"family": "Minelli", "given": "Matteo", "initials": "M", "orcid": "0000-0003-4662-1526", "researcher": {"href": "https://publications.scilifelab.se/researcher/44301a57b0704c90b546a7ef985dd73e.json"}}, {"family": "Lerch", "given": "Sarah", "initials": "S", "orcid": "0000-0001-5968-8178", "researcher": {"href": "https://publications.scilifelab.se/researcher/e192f96f7cb74b96985567fa2c099bf1.json"}}, {"family": "Tanyeli", "given": "Irem", "initials": "I", "orcid": "0000-0002-5433-2524", "researcher": {"href": "https://publications.scilifelab.se/researcher/ef5582c8609543d3a79f54d0948f3829.json"}}, {"family": "Lund", "given": "Anja", "initials": "A"}, {"family": "Andersson", "given": "Olof", "initials": "O"}, {"family": "Zhdanov", "given": "Vladimir P", "initials": "VP"}, {"family": "Liebi", "given": "Marianne", "initials": "M", "orcid": "0000-0002-5403-0593", "researcher": {"href": "https://publications.scilifelab.se/researcher/a404e64ffe7c47e0ac15819102c38279.json"}}, {"family": "Moth-Poulsen", "given": "Kasper", "initials": "K", "orcid": "0000-0003-4018-4927", "researcher": {"href": "https://publications.scilifelab.se/researcher/5807cc241ba24cf4a7841086d72dc3b9.json"}}, {"family": "M\u00fcller", "given": "Christian", "initials": "C", "orcid": "0000-0001-7859-7909", "researcher": {"href": "https://publications.scilifelab.se/researcher/7fc06198eb0c4a3eb17d052d8ef124ae.json"}}, {"family": "Langhammer", "given": "Christoph", "initials": "C", "orcid": "0000-0003-2180-1379", "researcher": {"href": "https://publications.scilifelab.se/researcher/17178716c3964e53933ddacffe70cc9a.json"}}], "type": "journal-article", "published": "2020-08-28", "journal": {"title": "ACS Appl. Nano Mater.", "issn": "2574-0970", "volume": "3", "issue": "8", "pages": "8438-8445", "issn-l": null}, "abstract": null, "doi": "10.1021/acsanm.0c01907", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2023-02-16T08:06:16.750Z", "modified": "2023-06-19T13:38:29.309Z"}, {"entity": "publication", "iuid": "0762dde157384547b4115c069024cfd4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0762dde157384547b4115c069024cfd4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0762dde157384547b4115c069024cfd4"}}, "title": "Leveraging a gain-of-function allele of Caenorhabditis elegans paqr-1 to elucidate membrane homeostasis by PAQR proteins.", "authors": [{"family": "Busayavalasa", "given": "Kiran", "initials": "K"}, {"family": "Ruiz", "given": "Mario", "initials": "M", "orcid": "0000-0002-7149-6600", "researcher": {"href": "https://publications.scilifelab.se/researcher/35ea5372ccf64bad864d90e4b3698a24.json"}}, {"family": "Devkota", "given": "Ranjan", "initials": "R"}, {"family": "St\u00e5hlman", "given": "Marcus", "initials": "M", "orcid": "0000-0002-4202-0339", "researcher": {"href": "https://publications.scilifelab.se/researcher/01a323cbf0a24269bd32bfc34539e021.json"}}, {"family": "Bodhicharla", "given": "Rakesh", "initials": "R", "orcid": "0000-0002-2344-6318", "researcher": {"href": "https://publications.scilifelab.se/researcher/576a63da68ef49b1a6ff2052398029c3.json"}}, {"family": "Svensk", "given": "Emma", "initials": "E"}, {"family": "Hermansson", "given": "Nils-Olov", "initials": "NO", "orcid": "0000-0003-0170-6649", "researcher": {"href": "https://publications.scilifelab.se/researcher/55f9c6644b354a4891f528786cf81628.json"}}, {"family": "Bor\u00e9n", "given": "Jan", "initials": "J", "orcid": "0000-0003-0786-8091", "researcher": {"href": "https://publications.scilifelab.se/researcher/1e85f6d287ce4c60a7b35b287efb4f79.json"}}, {"family": "Pilon", "given": "Marc", "initials": "M", "orcid": "0000-0003-3919-2882", "researcher": {"href": "https://publications.scilifelab.se/researcher/d45c4ecf9afe463c971af2de53a770a8.json"}}], "type": "journal article", "published": "2020-08-00", "journal": {"title": "PLoS Genet.", "issn": "1553-7404", "volume": "16", "issue": "8", "pages": "e1008975", "issn-l": "1553-7390"}, "abstract": "The C. elegans proteins PAQR-2 (a homolog of the human seven-transmembrane domain AdipoR1 and AdipoR2 proteins) and IGLR-2 (a homolog of the mammalian LRIG proteins characterized by a single transmembrane domain and the presence of immunoglobulin domains and leucine-rich repeats in their extracellular portion) form a complex that protects against plasma membrane rigidification by promoting the expression of fatty acid desaturases and the incorporation of polyunsaturated fatty acids into phospholipids, hence increasing membrane fluidity. In the present study, we leveraged a novel gain-of-function allele of PAQR-1, a PAQR-2 paralog, to carry out structure-function studies. We found that the transmembrane domains of PAQR-2 are responsible for its functional requirement for IGLR-2, that PAQR-1 does not require IGLR-2 but acts via the same pathway as PAQR-2, and that the divergent N-terminal cytoplasmic domains of the PAQR-1 and PAQR-2 proteins serve a regulatory function and may regulate access to the catalytic site of these proteins. We also show that overexpression of human AdipoR1 or AdipoR2 alone is sufficient to confer increased palmitic acid resistance in HEK293 cells, and thus act in a manner analogous to the PAQR-1 gain-of-function allele.", "doi": "10.1371/journal.pgen.1008975", "pmid": "32750056", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7428288"}, {"db": "pii", "key": "PGENETICS-D-20-00388"}], "notes": [], "created": "2023-02-16T08:05:11.834Z", "modified": "2023-02-16T08:05:11.984Z"}, {"entity": "publication", "iuid": "aaf4daf85306445fb1289969ce10aa94", "links": {"self": {"href": "https://publications.scilifelab.se/publication/aaf4daf85306445fb1289969ce10aa94.json"}, "display": {"href": "https://publications.scilifelab.se/publication/aaf4daf85306445fb1289969ce10aa94"}}, "title": "Label\u2010free laser scanning microscopy targeting sentinel lymph node diagnostics: A feasibility study ex vivo", "authors": [{"family": "Kantere", "given": "Despoina", "initials": "D", "orcid": "0000-0001-9133-8581", "researcher": {"href": "https://publications.scilifelab.se/researcher/caafe30bd22040cf8a7043f692366fe3.json"}}, {"family": "Siarov", "given": "Jan", "initials": "J"}, {"family": "De Lara", "given": "Shahin", "initials": "S"}, {"family": "Parhizkar", "given": "Samad", "initials": "S"}, {"family": "Olofsson Bagge", "given": "Roger", "initials": "R"}, {"family": "Wennberg Lark\u00f6", "given": "Ann\u2010Marie", "initials": "A"}, {"family": "Ericson", "given": "Marica B", "initials": "MB"}], "type": "journal-article", "published": "2020-08-00", "journal": {"title": "Translational Biophotonics", "issn": "2627-1850", "volume": "2", "issue": "3", "issn-l": null}, "abstract": null, "doi": "10.1002/tbio.202000002", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2023-02-16T08:07:51.640Z", "modified": "2023-06-19T13:38:39.647Z"}, {"entity": "publication", "iuid": "80d309ad52724e478307f7267291dec2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/80d309ad52724e478307f7267291dec2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/80d309ad52724e478307f7267291dec2"}}, "title": "First evidence of microbial wood degradation in the coastal waters of the Antarctic.", "authors": [{"family": "Bj\u00f6rdal", "given": "Charlotte G", "initials": "CG"}, {"family": "Dayton", "given": "Paul K", "initials": "PK"}], "type": "journal article", "published": "2020-07-29", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "12774", "issn-l": "2045-2322"}, "abstract": "Wood submerged in saline and oxygenated marine waters worldwide is efficiently degraded by crustaceans and molluscs. Nevertheless, in the cold coastal waters of the Antarctic, these degraders seem to be absent and no evidence of other wood-degrading organisms has been reported so far. Here we examine long-term exposed anthropogenic wood material (Douglas Fir) collected at the seafloor close to McMurdo station, Antarctica. We used light and scanning electron microscopy and demonstrate that two types of specialized lignocellulolytic microbes-soft rot fungi and tunnelling bacteria-are active and degrade wood in this extreme environment. Fungal decay dominates and hyphae penetrate the outer 2-4 mm of the wood surface. Decay rates observed are about two orders of magnitude lower than normal. The fungi and bacteria, as well as their respective cavities and tunnels, are slightly smaller than normal, which might represent an adaptation to the extreme cold environment. Our results establish that there is ongoing wood degradation also in the Antarctic, albeit at a vastly reduced rate compared to warmer environments. Historical shipwrecks resting on the seafloor are most likely still in good condition, although surface details such as wood carvings, tool marks, and paint slowly disintegrate due to microbial decay.", "doi": "10.1038/s41598-020-68613-y", "pmid": "32728072", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7391713"}, {"db": "pii", "key": "10.1038/s41598-020-68613-y"}], "notes": [], "created": "2023-02-16T08:04:18.196Z", "modified": "2023-02-16T08:04:18.198Z"}, {"entity": "publication", "iuid": "4b7619de4223442c97116b35b0c7402c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4b7619de4223442c97116b35b0c7402c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4b7619de4223442c97116b35b0c7402c"}}, "title": "Extracellular vesicles from human mesenchymal stem cells expedite chondrogenesis in 3D human degenerative disc cell cultures.", "authors": [{"family": "Hingert", "given": "Daphne", "initials": "D", "orcid": "0000-0002-8917-4458", "researcher": {"href": "https://publications.scilifelab.se/researcher/39bff3945f184267b4360bb086322e3c.json"}}, {"family": "Ekstr\u00f6m", "given": "Karin", "initials": "K"}, {"family": "Aldridge", "given": "Jonathan", "initials": "J"}, {"family": "Crescitelli", "given": "Rosella", "initials": "R"}, {"family": "Brisby", "given": "Helena", "initials": "H"}], "type": "journal article", "published": "2020-07-29", "journal": {"title": "Stem Cell Res Ther", "issn": "1757-6512", "volume": "11", "issue": "1", "pages": "323", "issn-l": "1757-6512"}, "abstract": "Extracellular vesicles (EVs) from human mesenchymal stem cells (hMSCs) are known to be mediators of intercellular communication and have been suggested as possible therapeutic agents in many diseases. Their potential use in intervertebral disc (IVD) degeneration associated with low back pain (LBP) is yet to be explored. Since LBP affects more than 85% of the western population resulting in high socioeconomic consequences, there is a demand for exploring new and possibly mini-invasive treatment alternatives. In this study, the effect of hMSC-derived small EVs (sEVs) on degenerated disc cells (DCs) isolated from patients with degenerative discs and chronic LBP was investigated in a 3D in vitro model.\n\nhMSCs were isolated from bone marrow aspirate, and EVs were isolated from conditioned media of the hMSCs by differential centrifugation and filtration. 3D pellet cultures of DCs were stimulated with the sEVs at 5 \u00d7 1010 vesicles/ml concentration for 28 days and compared to control. The pellets were harvested at days 7, 14, and 28 and evaluated for cell proliferation, viability, ECM production, apoptotic activity, chondrogenesis, and cytokine secretions.\n\nThe findings demonstrated that treatment with sEVs from hMSCs resulted in more than 50% increase in cell proliferation and decrease in cellular apoptosis in degenerated DCs from this patient group. ECM production was also observed as early as in day 7 and was more than three times higher in the sEV-treated DC pellets compared to control cultures. Further, sEV treatment suppressed secretion of MMP-1 in the DCs.\n\nhMSC-derived sEVs improved cell viability and expedited chondrogenesis in DCs from degenerated IVDs. These findings open up for new tissue regeneration treatment strategies to be developed for degenerative disorders of the spine.", "doi": "10.1186/s13287-020-01832-2", "pmid": "32727623", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7391655"}, {"db": "pii", "key": "10.1186/s13287-020-01832-2"}], "notes": [], "created": "2023-02-16T08:07:16.860Z", "modified": "2023-02-16T08:07:17.111Z"}, {"entity": "publication", "iuid": "2630e0f636f441ac9c35de34528196eb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2630e0f636f441ac9c35de34528196eb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2630e0f636f441ac9c35de34528196eb"}}, "title": "Decellularization and recellularization of the ovary for bioengineering applications; studies in the mouse.", "authors": [{"family": "Alshaikh", "given": "Ahmed Baker", "initials": "AB"}, {"family": "Padma", "given": "Arvind Manikantan", "initials": "AM"}, {"family": "Dehlin", "given": "Matilda", "initials": "M"}, {"family": "Akouri", "given": "Randa", "initials": "R"}, {"family": "Song", "given": "Min Jong", "initials": "MJ"}, {"family": "Br\u00e4nnstr\u00f6m", "given": "Mats", "initials": "M"}, {"family": "Hellstr\u00f6m", "given": "Mats", "initials": "M", "orcid": "0000-0003-3323-5618", "researcher": {"href": "https://publications.scilifelab.se/researcher/b41c54e9336c444d9de92c43a3330c9e.json"}}], "type": "journal article", "published": "2020-07-23", "journal": {"title": "Reprod Biol Endocrinol", "issn": "1477-7827", "volume": "18", "issue": "1", "pages": "75", "issn-l": null}, "abstract": "Fertility preservation is particularly challenging in young women diagnosed with hematopoietic cancers, as transplantation of cryopreserved ovarian cortex in these women carries the risk for re-introducing cancer cells. Therefore, the construction of a bioengineered ovary that can accommodate isolated small follicles was proposed as an alternative to minimize the risk of malignancy transmission. Various options for viable bioengineered scaffolds have been reported in the literature. Previously, we reported three protocols for producing mouse ovarian scaffolds with the decellularization technique. The present study examined these scaffolds further, specifically with regards to their extracellular composition, biocompatibility and ability to support recellularization with mesenchymal stem cells.\n\nThree decellularization protocols based on 0.5% sodium dodecyl sulfate (Protocol 1; P1), or 2% sodium deoxycholate (P2), or a combination of the two detergents (P3) were applied to produce three types of scaffolds. The levels of collagen, elastin and sulfated glycosaminoglycans (sGAGs) were quantified in the remaining extracellular matrix. Detailed immunofluorescence and scanning electron microscopy imaging were conducted to assess the morphology and recellularization efficiency of the constructs after 14 days in vitro utilizing red fluorescent protein-labelled mesenchymal stem cells.\n\nAll protocols efficiently removed the DNA while the elastin content was not significantly reduced during the procedures. The SDS-protocol (P1) reduced the sGAG and the collagen content more than the SDC-protocol (P2). All scaffolds were biocompatible and recellularization was successful, particularly in several P2-derived scaffolds. The cells were extensively distributed throughout the constructs, with a denser distribution observed towards the ovarian cortex. The cell density was not significantly different (400 to 550 cells/mm2) between scaffold types. However, there was a tendency towards a higher cell density in the SDC-derived constructs. Scanning electron microscope images showed fibrous scaffolds with a dense repopulated surface structure.\n\nWhile there were differences in the key structural macromolecules between protocols, all scaffolds were biocompatible and showed effective recellularization. The results indicate that our SDC-protocol might be better than our SDS-protocol. However, additional studies are necessary to determine their suitability for attachment of small follicles and folliculogenesis.", "doi": "10.1186/s12958-020-00630-y", "pmid": "32703228", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7376865"}, {"db": "pii", "key": "10.1186/s12958-020-00630-y"}], "notes": [], "created": "2023-02-16T08:02:26.716Z", "modified": "2023-02-16T08:02:26.784Z"}, {"entity": "publication", "iuid": "ee18a396f79f4e90a668a1318fc73ed8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ee18a396f79f4e90a668a1318fc73ed8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ee18a396f79f4e90a668a1318fc73ed8"}}, "title": "Amyloid precursor protein-b facilitates cell adhesion during early development in zebrafish.", "authors": [{"family": "Banote", "given": "Rakesh Kumar", "initials": "RK"}, {"family": "Chebli", "given": "Jasmine", "initials": "J"}, {"family": "\u015eat\u0131r", "given": "Tu\u011f\u00e7e Munise", "initials": "TM"}, {"family": "Varshney", "given": "Gaurav K", "initials": "GK", "orcid": "0000-0002-0429-1904", "researcher": {"href": "https://publications.scilifelab.se/researcher/a5b107029a9844de8b103873831b54f2.json"}}, {"family": "Camacho", "given": "Rafael", "initials": "R", "orcid": "0000-0003-2325-6407", "researcher": {"href": "https://publications.scilifelab.se/researcher/6a7a8cfe28634821984b078ce3246343.json"}}, {"family": "Ledin", "given": "Johan", "initials": "J", "orcid": "0000-0002-7319-7735", "researcher": {"href": "https://publications.scilifelab.se/researcher/92e482abc18c49d881d3bf0132b3fbcd.json"}}, {"family": "Burgess", "given": "Shawn M", "initials": "SM", "orcid": "0000-0003-1147-0596", "researcher": {"href": "https://publications.scilifelab.se/researcher/bf85532f49bc4208b7e456d4ee2e8f76.json"}}, {"family": "Abramsson", "given": "Alexandra", "initials": "A", "orcid": "0000-0002-4715-9225", "researcher": {"href": "https://publications.scilifelab.se/researcher/7abde12dab2e4d338bc6e55933f07531.json"}}, {"family": "Zetterberg", "given": "Henrik", "initials": "H"}], "type": "journal article", "published": "2020-06-23", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "10", "issue": "1", "pages": "10127", "issn-l": "2045-2322"}, "abstract": "Understanding the biological function of amyloid beta (A\u03b2) precursor protein (APP) beyond its role in Alzheimer's disease is emerging. Yet, its function during embryonic development is poorly understood. The zebrafish APP orthologue, Appb, is strongly expressed during early development but thus far has only been studied via morpholino-mediated knockdown. Zebrafish enables analysis of cellular processes in an ontogenic context, which is limited in many other vertebrates. We characterized zebrafish carrying a homozygous mutation that introduces a premature stop in exon 2 of the appb gene. We report that appb mutants are significantly smaller until 2 dpf and display perturbed enveloping layer (EVL) integrity and cell protrusions at the blastula stage. Moreover, appb mutants surviving beyond 48 hpf exhibited no behavioral defects at 6 dpf and developed into healthy and fertile adults. The expression of the app family member, appa, was also found to be altered in appb mutants. Taken together, we show that appb is involved in the initial development of zebrafish by supporting the integrity of the EVL, likely by mediating cell adhesion properties. The loss of Appb might then be compensated for by other app family members to maintain normal development.", "doi": "10.1038/s41598-020-66584-8", "pmid": "32576936", "labels": {"Genome Engineering Zebrafish": "Collaborative", "Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7311384"}, {"db": "pii", "key": "10.1038/s41598-020-66584-8"}], "notes": [], "created": "2020-06-24T09:03:55.674Z", "modified": "2023-02-16T08:03:52.996Z"}, {"entity": "publication", "iuid": "0006dd06fdae4e958b22569ce4577e4e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0006dd06fdae4e958b22569ce4577e4e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0006dd06fdae4e958b22569ce4577e4e"}}, "title": "T2 and T17 cytokines alter the cargo and function of airway epithelium-derived extracellular vesicles.", "authors": [{"family": "Ax", "given": "Elisabeth", "initials": "E", "orcid": "0000-0001-7553-5059", "researcher": {"href": "https://publications.scilifelab.se/researcher/3c2961415fa942a2b18c7272da4d91e4.json"}}, {"family": "Jevnikar", "given": "Zala", "initials": "Z"}, {"family": "Cvjetkovic", "given": "Aleksander", "initials": "A", "orcid": "0000-0002-9131-9791", "researcher": {"href": "https://publications.scilifelab.se/researcher/166451e5c8e54c0da297f6238c42c334.json"}}, {"family": "Malmh\u00e4ll", "given": "Carina", "initials": "C", "orcid": "0000-0001-6696-7570", "researcher": {"href": "https://publications.scilifelab.se/researcher/11c1a836d6d64df78e044403f9cc01db.json"}}, {"family": "Olsson", "given": "Henric", "initials": "H"}, {"family": "R\u00e5dinger", "given": "Madeleine", "initials": "M", "orcid": "0000-0002-0652-7378", "researcher": {"href": "https://publications.scilifelab.se/researcher/f8e9972bdb3b4d99a77a8c1fed528e21.json"}}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C", "orcid": "0000-0003-1279-1746", "researcher": {"href": "https://publications.scilifelab.se/researcher/e14e17d2cdb24a9f93991d83811c78b9.json"}}], "type": "journal article", "published": "2020-06-19", "journal": {"title": "Respir. Res.", "issn": "1465-993X", "volume": "21", "issue": "1", "pages": "155", "issn-l": "1465-9921"}, "abstract": "Asthma is a common and heterogeneous disease that includes subgroups characterized by type 2 (T2) or type 17 (T17) immune responses for which there is a need to identify the underlying mechanisms and biomarkers in order to develop specific therapies. These subgroups can be defined by airway epithelium gene signatures and the airway epithelium has also been implicated to play a significant role in asthma pathology. Extracellular vesicles (EVs) carry functional biomolecules and participate in cell-to-cell communication in both health and disease, properties that are likely to be involved in airway diseases such as asthma. The aim of this study was to identify stimulus-specific proteins and functionality of bronchial epithelium-derived EVs following stimulation with T2 or T17 cytokines.\n\nEVs from cytokine-stimulated (T2: IL-4 + IL-13 or T17: IL-17A + TNF\u03b1) human bronchial epithelial cells cultured at air-liquid interface (HBEC-ALI) were isolated by density cushion centrifugation and size exclusion chromatography and characterized with Western blotting and electron microscopy. Transcriptomic (cells) and proteomic (EVs) profiling was also performed.\n\nOur data shows that EVs are secreted and can be isolated from the apical side of HBEC-ALI and that cytokine stimulation increases EV release. Genes upregulated in cells stimulated with T2 or T17 cytokines were increased also on protein level in the EVs. Proteins found in T17-derived EVs were suggested to be involved in pathways related to neutrophil movement which was supported by assessing neutrophil chemotaxis ex vivo.\n\nTogether, the results suggest that epithelial EVs are involved in airway inflammation and that the EV proteome may be used for discovery of disease-specific mechanisms and signatures which may enable a precision medicine approach to the treatment of asthma.", "doi": "10.1186/s12931-020-01402-3", "pmid": "32560723", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7304225"}, {"db": "pii", "key": "10.1186/s12931-020-01402-3"}], "notes": [], "created": "2023-02-16T08:02:58.189Z", "modified": "2023-02-16T08:02:58.445Z"}, {"entity": "publication", "iuid": "60cb5c21673847068a71fc34addf5983", "links": {"self": {"href": "https://publications.scilifelab.se/publication/60cb5c21673847068a71fc34addf5983.json"}, "display": {"href": "https://publications.scilifelab.se/publication/60cb5c21673847068a71fc34addf5983"}}, "title": "Normal murine respiratory tract has its mucus concentrated in clouds based on the Muc5b mucin.", "authors": [{"family": "Fakih", "given": "Dalia", "initials": "D"}, {"family": "Rodriguez-Pi\u00f1eiro", "given": "Ana M", "initials": "AM"}, {"family": "Trillo-Muyo", "given": "Sergio", "initials": "S"}, {"family": "Evans", "given": "Christopher M", "initials": "CM"}, {"family": "Ermund", "given": "Anna", "initials": "A"}, {"family": "Hansson", "given": "Gunnar C", "initials": "GC"}], "type": "journal article", "published": "2020-06-01", "journal": {"title": "Am J Physiol Lung Cell Mol Physiol", "issn": "1522-1504", "volume": "318", "issue": "6", "pages": "L1270-L1279", "issn-l": null}, "abstract": "The organization of the normal airway mucus system differs in small experimental animals from that in humans and large mammals. To address normal murine airway mucociliary clearance, Alcian blue-stained mucus transport was measured ex vivo on tracheal tissues of na\u00efve C57BL/6, Muc5b-/-, Muc5ac-/-, and EGFP-tagged Muc5b reporter mice. Close to the larynx with a few submucosal glands, the mucus appeared as thick bundles. More distally in the trachea and in large bronchi, Alcian blue-stained mucus was organized in cloud-like formations based on the Muc5b mucin. On tilted tissue, the mucus clouds moved upward toward the larynx with an average velocity of 12 \u00b5m/s compared with 20 \u00b5m/s for beads not associated with clouds. In Muc5ac-/- mice, Muc5b formed mucus strands attached to the tissue surface, while in Muc5b-/- mice, Muc5ac had a more variable appearance. The normal mouse lung mucus thus appears as discontinuous clouds, clearly different from the stagnant mucus layer in diseased lungs.", "doi": "10.1152/ajplung.00485.2019", "pmid": "32348677", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7347266"}], "notes": [], "created": "2023-02-16T08:06:59.330Z", "modified": "2023-02-16T08:06:59.332Z"}, {"entity": "publication", "iuid": "70b66fc8c9d14a6bbdea4ed197d9f280", "links": {"self": {"href": "https://publications.scilifelab.se/publication/70b66fc8c9d14a6bbdea4ed197d9f280.json"}, "display": {"href": "https://publications.scilifelab.se/publication/70b66fc8c9d14a6bbdea4ed197d9f280"}}, "title": "Evolutionary Analysis of the Bacillus subtilis Genome Reveals New Genes Involved in Sporulation.", "authors": [{"family": "Shi", "given": "Lei", "initials": "L"}, {"family": "Derouiche", "given": "Abderahmane", "initials": "A"}, {"family": "Pandit", "given": "Santosh", "initials": "S"}, {"family": "Rahimi", "given": "Shadi", "initials": "S"}, {"family": "Kalantari", "given": "Aida", "initials": "A"}, {"family": "Futo", "given": "Momir", "initials": "M"}, {"family": "Ravikumar", "given": "Vaishnavi", "initials": "V"}, {"family": "Jers", "given": "Carsten", "initials": "C"}, {"family": "Mokkapati", "given": "Venkata R S S", "initials": "VRSS"}, {"family": "Vlahovi\u010dek", "given": "Kristian", "initials": "K"}, {"family": "Mijakovic", "given": "Ivan", "initials": "I"}], "type": "journal article", "published": "2020-06-01", "journal": {"title": "Mol. Biol. Evol.", "issn": "1537-1719", "volume": "37", "issue": "6", "pages": "1667-1678", "issn-l": "0737-4038"}, "abstract": "Bacilli can form dormant, highly resistant, and metabolically inactive spores to cope with extreme environmental challenges. In this study, we examined the evolutionary age of Bacillus subtilis sporulation genes using the approach known as genomic phylostratigraphy. We found that B. subtilis sporulation genes cluster in several groups that emerged at distant evolutionary time-points, suggesting that the sporulation process underwent several stages of expansion. Next, we asked whether such evolutionary stratification of the genome could be used to predict involvement in sporulation of presently uncharacterized genes (y-genes). We individually inactivated a representative sample of uncharacterized genes that arose during the same evolutionary periods as the known sporulation genes and tested the resulting strains for sporulation phenotypes. Sporulation was significantly affected in 16 out of 37 (43%) tested strains. In addition to expanding the knowledge base on B. subtilis sporulation, our findings suggest that evolutionary age could be used to help with genome mining.", "doi": "10.1093/molbev/msaa035", "pmid": "32061128", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7426031"}, {"db": "pii", "key": "5736554"}], "notes": [], "created": "2023-02-16T08:08:51.363Z", "modified": "2023-02-16T08:08:51.365Z"}, {"entity": "publication", "iuid": "72e9b85908ed435d8265e945883e4b04", "links": {"self": {"href": "https://publications.scilifelab.se/publication/72e9b85908ed435d8265e945883e4b04.json"}, "display": {"href": "https://publications.scilifelab.se/publication/72e9b85908ed435d8265e945883e4b04"}}, "title": "Alterations of endometrial epithelial-mesenchymal transition and MAPK signalling components in women with PCOS are partially modulated by metformin in vitro.", "authors": [{"family": "Hu", "given": "Min", "initials": "M"}, {"family": "Zhang", "given": "Yuehui", "initials": "Y"}, {"family": "Li", "given": "Xin", "initials": "X"}, {"family": "Cui", "given": "Peng", "initials": "P"}, {"family": "Li", "given": "Juan", "initials": "J"}, {"family": "Br\u00e4nnstr\u00f6m", "given": "Mats", "initials": "M"}, {"family": "Shao", "given": "Linus R", "initials": "LR"}, {"family": "Billig", "given": "H\u00e5kan", "initials": "H"}], "type": "journal article", "published": "2020-05-15", "journal": {"title": "Mol. Hum. Reprod.", "issn": "1460-2407", "volume": "26", "issue": "5", "pages": "312-326", "issn-l": "1360-9947"}, "abstract": "Growing evidence suggests that epithelial-mesenchymal transition (EMT) and its regulator mitogen-activated protein kinase (MAPK) contribute to endometria-related reproductive disorders. However, the regulation of EMT and MAPK signalling components in the endometrium from polycystic ovary syndrome (PCOS) patients has not been systematically investigated and remains elusive. In humans, how metformin induces molecular alterations in the endometrial tissues under PCOS conditions is not completely clear. Here, we recruited 7 non-PCOS patients during the proliferative phase (nPCOS), 7 non-PCOS patients with endometrial hyperplasia (nPCOSEH), 14 PCOS patients during the proliferative phase (PCOS) and 3 PCOS patients with endometrial hyperplasia (PCOSEH). Our studies demonstrated that compared with nPCOS, PCOS patients showed decreased Claudin 1 and increased Vimentin and Slug proteins. Similar to increased Slug protein, nPCOSEH and PCOSEH patients showed increased N-cadherin protein. Western blot and immunostaining revealed increased epithelial phosphorylated Cytokeratin 8 (p-CK 8) expression and an increased p-CK 8:CK 8 ratio in PCOS, nPCOSEH and PCOSEH patients compared to nPCOS patients. Although nPCOSEH and PCOSEH patients showed increased p-ERK1/2 and/or p38 protein levels, the significant increase in p-ERK1/2 expression and p-ERK1/2:ERK1/2 ratio was only found in PCOS patients compared to nPCOS patients. A significant induction of the membrane ER\u03b2 immunostaining was observed in the epithelial cells of PCOS and PCOSEH patients compared to nPCOS and nPCOSEH patients. While in vitro treatment with metformin alone increased Snail and decreased Claudin 1, N-cadherin and \u03b1-SMA proteins, concomitant treatment with metformin and E2 increased the expression of CK 8 and Snail proteins and decreased the expression of Claudin 1, ZO-1, Slug and \u03b1-SMA proteins. Our findings suggest that the EMT contributes to the switch from a healthy state to a PCOS state in the endometrium, which might subsequently drive endometrial injury and dysfunction. We also provide evidence that metformin differentially modulates EMT protein expression in PCOS patients depending on oestrogenic stimulation.", "doi": "10.1093/molehr/gaaa023", "pmid": "32202622", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "5810989"}], "notes": [], "created": "2023-02-16T08:07:26.139Z", "modified": "2023-02-16T08:07:26.154Z"}, {"entity": "publication", "iuid": "833e03625bc74a739758ff27bcb82ea2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/833e03625bc74a739758ff27bcb82ea2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/833e03625bc74a739758ff27bcb82ea2"}}, "title": "Isolation and characterization of microvesicles from mesenchymal stem cells.", "authors": [{"family": "Mohammadi", "given": "M Rezaa", "initials": "MR"}, {"family": "Riazifar", "given": "Milad", "initials": "M"}, {"family": "Pone", "given": "Egest J", "initials": "EJ"}, {"family": "Yeri", "given": "Ashish", "initials": "A"}, {"family": "Van Keuren-Jensen", "given": "Kendall", "initials": "K"}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C"}, {"family": "Lotvall", "given": "Jan", "initials": "J"}, {"family": "Zhao", "given": "Weian", "initials": "W"}], "type": "journal article", "published": "2020-05-01", "journal": {"title": "Methods", "issn": "1095-9130", "volume": "177", "issue": null, "pages": "50-57", "issn-l": "1046-2023"}, "abstract": "Mesenchymal stem or stromal cells are currently under clinical investigation for multiple diseases. While their mechanism of action is still not fully elucidated, vesicles secreted by MSCs are believed to recapitulate their therapeutic potentials to some extent. Microvesicles (MVs), also called as microparticles or ectosome, are among secreted vesicles that could transfer cytoplasmic cargo, including RNA and proteins, from emitting (source) cells to recipient cells. Given the importance of MVs, we here attempted to establish a method to isolate and characterize MVs secreted from unmodified human bone marrow derived MSCs (referred to as native MSCs, and their microvesicles as Native-MVs) and IFN\u03b3 stimulated MSCs (referred to as IFN\u03b3-MSCs, and their microvesicles as IFN\u03b3-MVs). We first describe an ultracentrifugation technique to isolate MVs from the conditioned cell culture media of MSCs. Next, we describe characterization and quality control steps to analyze the protein and RNA content of MVs. Finally, we examined the potential of MVs to exert immunomodulatory effects through induction of regulatory T cells (Tregs). Secretory vesicles from MSCs are promising alternatives for cell therapy with applications in drug delivery, regenerative medicine, and immunotherapy.", "doi": "10.1016/j.ymeth.2019.10.010", "pmid": "31669353", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "mid", "key": "NIHMS1542355"}, {"db": "pmc", "key": "PMC7182501"}, {"db": "pii", "key": "S1046-2023(19)30226-9"}], "notes": [], "created": "2020-01-23T16:11:25.279Z", "modified": "2023-02-16T08:08:22.362Z"}, {"entity": "publication", "iuid": "c0a96e98a034428a81aa4c4d641f4022", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c0a96e98a034428a81aa4c4d641f4022.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c0a96e98a034428a81aa4c4d641f4022"}}, "title": "Extracellular vesicles from mast cells induce mesenchymal transition in airway epithelial cells.", "authors": [{"family": "Yin", "given": "Yanan", "initials": "Y"}, {"family": "Shelke", "given": "Ganesh Vilas", "initials": "GV"}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C"}, {"family": "Brismar", "given": "Hjalmar", "initials": "H", "orcid": "0000-0003-0578-4003", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ec23336e2ef4e298f340876f1136dce.json"}}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J"}], "type": "journal article", "published": "2020-05-01", "journal": {"volume": "21", "issn": "1465-993X", "issue": "1", "pages": "101", "title": "Respir. Res.", "issn-l": "1465-9921"}, "abstract": "In the airways, mast cells are present in close vicinity to epithelial cells, and they can interact with each other via multiple factors, including extracellular vesicles (EVs). Mast cell-derived EVs have a large repertoire of cargos, including proteins and RNA, as well as surface DNA. In this study, we hypothesized that these EVs can induce epithelial to mesenchymal transition (EMT) in airway epithelial cells.\n\nIn this in-vitro study we systematically determined the effects of mast cell-derived EVs on epithelial A549 cells. We determined the changes that are induced by EVs on A549 cells at both the RNA and protein levels. Moreover, we also analyzed the rapid changes in phosphorylation events in EV-recipient A549 cells using a phosphorylated protein microarray. Some of the phosphorylation-associated events associated with EMT were validated using immunoblotting.\n\nMorphological and transcript analysis of epithelial A549 cells indicated that an EMT-like phenotype was induced by the EVs. Transcript analysis indicated the upregulation of genes involved in EMT, including TWIST1, MMP9, TGFB1, and BMP-7. This was accompanied by downregulation of proteins such as E-cadherin and upregulation of Slug-Snail and matrix metalloproteinases. Additionally, our phosphorylated-protein microarray analysis revealed proteins associated with the EMT cascade that were upregulated after EV treatment. We also found that transforming growth factor beta-1, a well-known EMT inducer, is associated with EVs and mediates the EMT cascade induced in the A549 cells.\n\nMast cell-derived EVs mediate the induction of EMT in epithelial cells, and our evidence suggests that this is triggered through the induction of protein phosphorylation cascades.", "doi": "10.1186/s12931-020-01346-8", "pmid": "32357878", "labels": {"Integrated Microscopy Technologies Stockholm": "Service", "Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7193353"}, {"db": "pii", "key": "10.1186/s12931-020-01346-8"}], "notes": [], "created": "2020-05-28T09:37:08.201Z", "modified": "2023-02-16T08:10:14.450Z"}, {"entity": "publication", "iuid": "0ea80926bb3240349dae2e9cb5fb3448", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0ea80926bb3240349dae2e9cb5fb3448.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0ea80926bb3240349dae2e9cb5fb3448"}}, "title": "Monitoring calcium-induced epidermal differentiation in vitro using multiphoton microscopy.", "authors": [{"family": "Malak", "given": "Monika", "initials": "M"}, {"family": "Grantham", "given": "Julie", "initials": "J"}, {"family": "Ericson", "given": "Marica B", "initials": "MB"}], "type": "journal article", "published": "2020-05-00", "journal": {"title": "J Biomed Opt", "issn": "1560-2281", "volume": "25", "issue": "7", "pages": "1-11", "issn-l": null}, "abstract": "Research in tissue engineering and in vitro organ formation has recently intensified. To assess tissue morphology, the method of choice today is restricted primarily to histology. Thus novel tools are required to enable noninvasive, and preferably label-free, three-dimensional imaging that is more compatible with futuristic organ-on-a-chip models.\n\nWe investigate the potential for using multiphoton microscopy (MPM) as a label-free in vitro approach to monitor calcium-induced epidermal differentiation.\n\nIn vitro epidermis was cultured at the air-liquid interface in varying calcium concentrations. Morphology and tissue architecture were investigated using MPM based on visualizing cellular autofluorescence.\n\nDistinct morphologies corresponding to epidermal differentiation were observed. In addition, Ca2 + -induced effects could be distinguished based on the architectural differences in stratification in the tissue cultures.\n\nOur study shows that MPM based on cellular autofluorescence enables visualization of Ca2 + -induced differentiation in epidermal skin models in vitro. The technique has potential to be further adapted as a noninvasive, label-free, and real-time tool to monitor tissue regeneration and organ formation in vitro.", "doi": "10.1117/1.JBO.25.7.071205", "pmid": "32388932", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7210787"}, {"db": "pii", "key": "JBO-190345SSRR"}], "notes": [], "created": "2023-02-16T08:08:00.526Z", "modified": "2023-02-16T08:08:00.558Z"}, {"entity": "publication", "iuid": "b1e92191e1894e02ae64098f4f082a33", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b1e92191e1894e02ae64098f4f082a33.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b1e92191e1894e02ae64098f4f082a33"}}, "title": "Long-term stability of partial nitritation-anammox for treatment of municipal wastewater in a moving bed biofilm reactor pilot system.", "authors": [{"family": "Gustavsson", "given": "David J I", "initials": "DJI"}, {"family": "Suarez", "given": "Carolina", "initials": "C"}, {"family": "Wil\u00e9n", "given": "Britt-Marie", "initials": "BM"}, {"family": "Hermansson", "given": "Malte", "initials": "M"}, {"family": "Persson", "given": "Frank", "initials": "F"}], "type": "journal article", "published": "2020-04-20", "journal": {"title": "Sci. Total Environ.", "issn": "1879-1026", "volume": "714", "pages": "136342", "issn-l": "0048-9697"}, "abstract": "Nitrogen removal from the mainstream of municipal wastewater with partial nitritation-anammox (PNA) would be highly beneficial with regard to the uses of energy and organic carbon. However, the challenges of process instability, low nitrogen removal rates (NRR) and unwanted aerobic nitrite oxidation need to be solved to reach large-scale implementation. Here, we have operated pilot-scale moving bed biofilm reactors (MBBRs) for mainstream treatment, together with sidestream treatment of sludge liquor from anaerobic digestors, for over 900 days to investigate process stability, reactor performance and microbial community structure at realistic conditions. The MBBR biofilm contained stable and high relative abundances of anammox bacteria (10-32%) consisting of two major Brocadia sp. populations, and several populations of aerobic ammonia-oxidising bacteria (AOB) within Nitrosomonas sp. (0.2-3.1%), as assessed by 16S rDNA amplicon sequencing. In addition, nitrite-oxidising bacteria (NOB) consisting of Nitrospira sp. (0.4-0.8%) and Nitrotoga sp. (up to 0.4%) were present. Nitrogen was removed at a peak rate of 0.66 g N m-2 d-1 (0.13 kg N m-3 d-1) with a nitrate production over ammonium consumption of 15% by the NOB, at operation with continuous aeration at 15 \u00b0C. However, during most periods with continuous aeration, the NRR was lower (\u2248 0.45 g N m-2 d-1), with larger relative nitrate production (\u224840%), presumably due to problems to maintain stable residual ammonium concentrations during wet-weather mainstream flows. Changing reactor operation to intermittent aeration decreased the NRR but did not help in suppressing the NOB. The study shows that with MBBRs, stable mainstream PNA can be attained at realistic NRR, but with need for post-treatment of nitrate, since effective NOB suppression was hard to achieve.", "doi": "10.1016/j.scitotenv.2019.136342", "pmid": "31982771", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S0048-9697(19)36338-7"}], "notes": [], "created": "2023-02-16T08:07:06.862Z", "modified": "2023-02-16T08:07:06.874Z"}, {"entity": "publication", "iuid": "e21fd1cb40c740a098c9804b828e3a5c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e21fd1cb40c740a098c9804b828e3a5c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e21fd1cb40c740a098c9804b828e3a5c"}}, "title": "Towards uterus tissue engineering: a comparative study of sheep uterus decellularisation.", "authors": [{"family": "Tiemann", "given": "T T", "initials": "TT"}, {"family": "Padma", "given": "A M", "initials": "AM"}, {"family": "Sehic", "given": "E", "initials": "E"}, {"family": "B\u00e4ckdahl", "given": "H", "initials": "H"}, {"family": "Oltean", "given": "M", "initials": "M"}, {"family": "Song", "given": "M J", "initials": "MJ"}, {"family": "Br\u00e4nnstr\u00f6m", "given": "M", "initials": "M"}, {"family": "Hellstr\u00f6m", "given": "M", "initials": "M"}], "type": "comparative study", "published": "2020-03-26", "journal": {"title": "Mol. Hum. Reprod.", "issn": "1460-2407", "volume": "26", "issue": "3", "pages": "167-178", "issn-l": "1360-9947"}, "abstract": "Uterus tissue engineering may dismantle limitations in current uterus transplantation protocols. A uterine biomaterial populated with patient-derived cells could potentially serve as a graft to circumvent complicated surgery of live donors, immunosuppressive medication and rejection episodes. Repeated uterine bioengineering studies on rodents have shown promising results using decellularised scaffolds to restore fertility in a partially impaired uterus and now mandate experiments on larger and more human-like animal models. The aim of the presented studies was therefore to establish adequate protocols for scaffold generation and prepare for future in vivo sheep uterus bioengineering experiments. Three decellularisation protocols were developed using vascular perfusion through the uterine artery of whole sheep uteri obtained from slaughterhouse material. Decellularisation solutions used were based on 0.5% sodium dodecyl sulphate (Protocol 1) or 2% sodium deoxycholate (Protocol 2) or with a sequential perfusion of 2% sodium deoxycholate and 1% Triton X-100 (Protocol 3). The scaffolds were examined by histology, extracellular matrix quantification, evaluation of mechanical properties and the ability to support foetal sheep stem cells after recellularisation. We showed that a sheep uterus can successfully be decellularised while maintaining a high integrity of the extracellular components. Uteri perfused with sodium deoxycholate (Protocol 2) were the most favourable treatment in our study based on quantifications. However, all scaffolds supported stem cells for 2 weeks in vitro and showed no cytotoxicity signs. Cells continued to express markers for proliferation and maintained their undifferentiated phenotype. Hence, this study reports three valuable decellularisation protocols for future in vivo sheep uterus bioengineering experiments.", "doi": "10.1093/molehr/gaaa009", "pmid": "31980817", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7103571"}, {"db": "pii", "key": "5715759"}], "notes": [], "created": "2023-02-16T08:09:57.817Z", "modified": "2023-02-16T08:09:57.820Z"}, {"entity": "publication", "iuid": "36a139ec84d74001845f829037276801", "links": {"self": {"href": "https://publications.scilifelab.se/publication/36a139ec84d74001845f829037276801.json"}, "display": {"href": "https://publications.scilifelab.se/publication/36a139ec84d74001845f829037276801"}}, "title": "Chemical imaging of evolving amyloid plaque pathology and associated A\u03b2 peptide aggregation in a transgenic mouse model of Alzheimer's disease.", "authors": [{"family": "Michno", "given": "Wojciech", "initials": "W", "orcid": "0000-0002-3096-3604", "researcher": {"href": "https://publications.scilifelab.se/researcher/7b4307eb6e45426e8176337e88c9c344.json"}}, {"family": "Wehrli", "given": "Patrick", "initials": "P"}, {"family": "Meier", "given": "Silvio R", "initials": "SR"}, {"family": "Sehlin", "given": "Dag", "initials": "D"}, {"family": "Syv\u00e4nen", "given": "Stina", "initials": "S"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H", "orcid": "0000-0003-3930-4354", "researcher": {"href": "https://publications.scilifelab.se/researcher/85efee74eb4a4b38b63cf2823d204529.json"}}, {"family": "Blennow", "given": "Kaj", "initials": "K"}, {"family": "Hanrieder", "given": "J\u00f6rg", "initials": "J", "orcid": "0000-0001-6059-198X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e65454100674f98bf8f2575093f2441.json"}}], "type": "journal article", "published": "2020-03-00", "journal": {"title": "J. Neurochem.", "issn": "1471-4159", "volume": "152", "issue": "5", "pages": "602-616", "issn-l": "0022-3042"}, "abstract": "One of the major hallmarks of Alzheimer's disease (AD) pathology is the formation of extracellular amyloid \u03b2 (A\u03b2) plaques. While A\u03b2 has been suggested to be critical in inducing and, potentially, driving the disease, the molecular basis of AD pathogenesis is still under debate. Extracellular A\u03b2 plaque pathology manifests itself upon aggregation of distinct A\u03b2 peptides, resulting in morphologically different plaque morphotypes, including mainly diffuse and cored senile plaques. As plaque pathology precipitates long before any clinical symptoms occur, targeting the A\u03b2 aggregation processes provides a promising target for early interventions. However, the chain of events of when, where and what A\u03b2 species aggregate and form plaques remains unclear. The aim of this study was to investigate the potential of matrix-assisted laser desorption/ionization imaging mass spectrometry as a tool to study the evolving pathology in transgenic mouse models for AD. To that end, we used an emerging, chemical imaging modality - matrix-assisted laser desorption/ionization imaging mass spectrometry - that allows for delineating A\u03b2 aggregation with specificity at the single plaque level. We identified that plaque formation occurs first in cortical regions and that these younger plaques contain higher levels of 42 amino acid-long A\u03b2 (A\u03b21-42). Plaque maturation was found to be characterized by a relative increase in deposition of A\u03b21-40, which was associated with the appearance of a cored morphology for those plaques. Finally, other C-terminally truncated A\u03b2 species (A\u03b21-38 and A\u03b21-39) exhibited a similar aggregation pattern as A\u03b21-40, suggesting that these species have similar aggregation characteristics. These results suggest that initial plaque formation is seeded by A\u03b21-42; a process that is followed by plaque maturation upon deposition of A\u03b21-40 as well as deposition of other C-terminally modified A\u03b2 species.", "doi": "10.1111/jnc.14888", "pmid": "31605538", "labels": {"Integrated Microscopy Technologies Gothenburg": "Collaborative"}, "xrefs": [], "notes": [], "created": "2023-02-16T08:08:09.467Z", "modified": "2023-02-16T08:12:11.343Z"}, {"entity": "publication", "iuid": "9f85daf2c35c4935a50ff9ddf7732c78", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9f85daf2c35c4935a50ff9ddf7732c78.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9f85daf2c35c4935a50ff9ddf7732c78"}}, "title": "In Vitro Regeneration of Decellularized Pig Esophagus Using Human Amniotic Stem Cells.", "authors": [{"family": "Nayakawde", "given": "Nikhil B", "initials": "NB"}, {"family": "Methe", "given": "Ketaki", "initials": "K"}, {"family": "Banerjee", "given": "Debashish", "initials": "D"}, {"family": "Berg", "given": "Malin", "initials": "M"}, {"family": "Premaratne", "given": "Goditha U", "initials": "GU"}, {"family": "Olausson", "given": "Michael", "initials": "M"}], "type": "journal article", "published": "2020-02-21", "journal": {"title": "Biores Open Access", "issn": "2164-7844", "volume": "9", "issue": "1", "pages": "22-36", "issn-l": null}, "abstract": "Decellularization of esophagus was studied using three different protocols. The sodium deoxycholate/DNase-I (SDC/DNase-I) method was the most successful as evidenced by histology and DNA quantification of the acellular scaffolds. Acellular scaffolds were further analyzed and compared with native tissue by histology, quantitative analysis of DNA, and extracellular matrix (ECM) proteins. Histologically, the SDC/DNase-I protocol effectively produced scaffold with preserved structural architecture similar to native tissue architecture devoid of any cell nucleus. ECM proteins, such as collagen, elastin, and glycosaminoglycans were present even after detergent-enzymatic decellularization. Immunohistochemical analysis of acellular scaffold showed weak expression of Gal 1, 3 Gal epitope compared with native tissue. For performing recellularization, human amnion-derived mesenchymal stem cells (MSCs) and epithelial cells were seeded onto acellular esophagus in a perfusion-rotation bioreactor. In recellularized esophagus, immunohistochemistry showed infiltration of MSCs from adventitia into the muscularis externa and differentiation of MSCs into the smooth muscle actin and few endothelial cells (CD31). Our study demonstrates successful preparation and characterization of a decellularized esophagus with reduced load of Gal 1, 3 Gal epitope with preserved architecture and ECM proteins similar to native tissue. Upon subsequent recellularization, xenogeneic acellular esophagus also supported stem cell growth and partial differentiation of stem cells. Hence, the current study offers the hope for preparing a tissue-engineered esophagus in vitro which can be transplanted further into pigs for further in vivo evaluation.", "doi": "10.1089/biores.2019.0054", "pmid": "32117597", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7047253"}, {"db": "pii", "key": "10.1089/biores.2019.0054"}], "notes": [], "created": "2023-02-16T08:08:30.830Z", "modified": "2023-02-16T08:08:30.859Z"}, {"entity": "publication", "iuid": "45731fef896f4c55814ee2668776f539", "links": {"self": {"href": "https://publications.scilifelab.se/publication/45731fef896f4c55814ee2668776f539.json"}, "display": {"href": "https://publications.scilifelab.se/publication/45731fef896f4c55814ee2668776f539"}}, "title": "Subpopulations of extracellular vesicles from human metastatic melanoma tissue identified by quantitative proteomics after optimized isolation.", "authors": [{"family": "Crescitelli", "given": "Rossella", "initials": "R", "orcid": "0000-0002-1714-3169", "researcher": {"href": "https://publications.scilifelab.se/researcher/1d4b955f26ca4a679deb090e30d0ccf1.json"}}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C", "orcid": "0000-0003-1279-1746", "researcher": {"href": "https://publications.scilifelab.se/researcher/e14e17d2cdb24a9f93991d83811c78b9.json"}}, {"family": "Jang", "given": "Su Chul", "initials": "SC", "orcid": "0000-0003-3326-1007", "researcher": {"href": "https://publications.scilifelab.se/researcher/d7866f9f05f74587af9a4d5beec0a1b5.json"}}, {"family": "Cvjetkovic", "given": "Aleksander", "initials": "A", "orcid": "0000-0002-9131-9791", "researcher": {"href": "https://publications.scilifelab.se/researcher/166451e5c8e54c0da297f6238c42c334.json"}}, {"family": "Malmh\u00e4ll", "given": "Carina", "initials": "C"}, {"family": "Karimi", "given": "Nasibeh", "initials": "N"}, {"family": "H\u00f6\u00f6g", "given": "Johanna L", "initials": "JL", "orcid": "0000-0003-2162-3816", "researcher": {"href": "https://publications.scilifelab.se/researcher/f1eaedff964f4060ae6e69f59cad4521.json"}}, {"family": "Johansson", "given": "Iva", "initials": "I", "orcid": "0000-0003-2162-3816", "researcher": {"href": "https://publications.scilifelab.se/researcher/f1eaedff964f4060ae6e69f59cad4521.json"}}, {"family": "Fuchs", "given": "Johannes", "initials": "J"}, {"family": "Thorsell", "given": "Annika", "initials": "A"}, {"family": "Gho", "given": "Yong Song", "initials": "YS"}, {"family": "Olofsson Bagge", "given": "R", "initials": "R", "orcid": "0000-0001-5795-0355", "researcher": {"href": "https://publications.scilifelab.se/researcher/e1f8016d5e64418ca71f230e64e415ba.json"}}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J", "orcid": "0000-0001-9195-9249", "researcher": {"href": "https://publications.scilifelab.se/researcher/0cbcaf6b5698411c92e0de9e8fcf390f.json"}}], "type": "journal article", "published": "2020-02-11", "journal": {"title": "J Extracell Vesicles", "issn": "2001-3078", "volume": "9", "issue": "1", "pages": "1722433", "issn-l": "2001-3078"}, "abstract": "The majority of extracellular vesicle (EV) studies conducted to date have been performed on cell lines with little knowledge on how well these represent the characteristics of EVs in vivo. The aim of this study was to establish a method to isolate and categorize subpopulations of EVs isolated directly from tumour tissue. First we established an isolation protocol for subpopulations of EVs from metastatic melanoma tissue, which included enzymatic treatment (collagenase D and DNase). Small and large EVs were isolated with differential ultracentrifugation, and these were further separated into high and low-density (HD and LD) fractions. All EV subpopulations were then analysed in depth using electron microscopy, Bioanalyzer\u00ae, nanoparticle tracking analysis, and quantitative mass spectrometry analysis. Subpopulations of EVs with distinct size, morphology, and RNA and protein cargo could be isolated from the metastatic melanoma tissue. LD EVs showed an RNA profile with the presence of 18S and 28S ribosomal subunits. In contrast, HD EVs had RNA profiles with small or no peaks for ribosomal RNA subunits. Quantitative proteomics showed that several proteins such as flotillin-1 were enriched in both large and small LD EVs, while ADAM10 were exclusively enriched in small LD EVs. In contrast, mitofilin was enriched only in the large EVs. We conclude that enzymatic treatments improve EV isolation from dense fibrotic tissue without any apparent effect on molecular or morphological characteristics. By providing a detailed categorization of several subpopulations of EVs isolated directly from tumour tissues, we might better understand the function of EVs in tumour biology and their possible use in biomarker discovery.", "doi": "10.1080/20013078.2020.1722433", "pmid": "32128073", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service", "Glycoproteomics and MS Proteomics": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC7034452"}, {"db": "pii", "key": "1722433"}], "notes": [], "created": "2023-02-16T08:05:59.349Z", "modified": "2024-01-16T13:46:30.980Z"}, {"entity": "publication", "iuid": "9d8c8b87548b47d385525da2c499b617", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9d8c8b87548b47d385525da2c499b617.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9d8c8b87548b47d385525da2c499b617"}}, "title": "Engineering yeast phospholipid metabolism for de novo oleoylethanolamide production.", "authors": [{"family": "Liu", "given": "Yi", "initials": "Y"}, {"family": "Liu", "given": "Quanli", "initials": "Q"}, {"family": "Krivoruchko", "given": "Anastasia", "initials": "A"}, {"family": "Khoomrung", "given": "Sakda", "initials": "S"}, {"family": "Nielsen", "given": "Jens", "initials": "J", "orcid": "0000-0002-9955-6003", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a596e289be4438a8a2653b1f25fea8b.json"}}], "type": "journal article", "published": "2020-02-00", "journal": {"title": "Nat. Chem. Biol.", "issn": "1552-4469", "volume": "16", "issue": "2", "pages": "197-205", "issn-l": "1552-4450"}, "abstract": "Phospholipids, the most abundant membrane lipid components, are crucial in maintaining membrane structures and homeostasis for biofunctions. As a structurally diverse and tightly regulated system involved in multiple organelles, phospholipid metabolism is complicated to manipulate. Thus, repurposing phospholipids for lipid-derived chemical production remains unexplored. Herein, we develop a Saccharomyces cerevisiae platform for de novo production of oleoylethanolamide, a phospholipid derivative with promising pharmacological applications in ameliorating lipid dysfunction and neurobehavioral symptoms. Through deregulation of phospholipid metabolism, screening of biosynthetic enzymes, engineering of subcellular trafficking and process optimization, we could produce oleoylethanolamide at a titer of 8,115.7 \u00b5g l-1 and a yield on glucose of 405.8 \u00b5g g-1. Our work provides a proof-of-concept study for systemically repurposing phospholipid metabolism for conversion towards value-added biological chemicals, and this multi-faceted framework may shed light on tailoring phospholipid metabolism in other microbial hosts.", "doi": "10.1038/s41589-019-0431-2", "pmid": "31844304", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41589-019-0431-2"}], "notes": [], "created": "2020-01-23T16:07:21.153Z", "modified": "2021-11-10T12:54:25.998Z"}, {"entity": "publication", "iuid": "cecdb027f8464e688356c1b0f1193c13", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cecdb027f8464e688356c1b0f1193c13.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cecdb027f8464e688356c1b0f1193c13"}}, "title": "Mitochondrial protein enriched extracellular vesicles discovered in human melanoma tissues can be detected in patient plasma", "authors": [{"family": "Jang", "given": "Su Chul", "initials": "SC"}, {"family": "Crescitelli", "given": "Rossella", "initials": "R"}, {"family": "Cvjetkovic", "given": "Aleksander", "initials": "A"}, {"family": "Belgrano", "given": "Valerio", "initials": "V"}, {"family": "Olofsson Bagge", "given": "Roger", "initials": "R"}, {"family": "Sundfeldt", "given": "Karin", "initials": "K"}, {"family": "Ochiya", "given": "Takahiro", "initials": "T"}, {"family": "Kalluri", "given": "Raghu", "initials": "R"}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J"}], "type": "journal-article", "published": "2019-12-01", "journal": {"volume": "8", "issn": "2001-3078", "issue": "1", "pages": "1635420", "title": "J Extracell Vesicles", "issn-l": "2001-3078"}, "abstract": "Extracellular vesicles (EVs), including exosomes and microvesicles, are secreted from all cells, and convey messages between cells in health and disease. However, the diversity of EV subpopulations is only beginning to be explored. Since EVs have been implicated in tumour microenvironmental communication, we started to determine the diversity of EVs specifically in this tissue. To do this, we isolated EVs directly from patient melanoma metastatic tissues. Using EV membrane isolation and mass spectrometry analysis, we discovered enrichment of mitochondrial membrane proteins in the melanoma tissue-derived EVs, compared to non-melanoma-derived EVs. Interestingly, two mitochondrial inner membrane proteins MT-CO2 (encoded by the mitochondrial genome) and COX6c (encoded by the nuclear genome) were highly prevalent in the plasma of melanoma patients, as well as in ovarian and breast cancer patients. Furthermore, this subpopulation of EVs contains active mitochondrial enzymes. In summary, tumour tissues are enriched in EVs with mitochondrial membrane proteins and these mitochondrial membrane proteins can be detected in plasma and are increased in melanoma, ovarian cancer as well as breast cancer.", "doi": "10.1080/20013078.2019.1635420", "pmid": "31497264", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service", "Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [], "notes": [], "created": "2020-01-23T16:03:37.690Z", "modified": "2024-01-16T13:46:31.082Z"}, {"entity": "publication", "iuid": "11d70d17cf8247439353be6f309727aa", "links": {"self": {"href": "https://publications.scilifelab.se/publication/11d70d17cf8247439353be6f309727aa.json"}, "display": {"href": "https://publications.scilifelab.se/publication/11d70d17cf8247439353be6f309727aa"}}, "title": "Endosomal signalling via exosome surface TGF\u03b2-1", "authors": [{"family": "Shelke", "given": "Ganesh Vilas", "initials": "GV"}, {"family": "Yin", "given": "Yanan", "initials": "Y"}, {"family": "Jang", "given": "Su Chul", "initials": "SC"}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C"}, {"family": "Wennmalm", "given": "Stefan", "initials": "S"}, {"family": "Hoffmann", "given": "Hans J\u00fcrgen", "initials": "HJ"}, {"family": "Li", "given": "Li", "initials": "L"}, {"family": "Gho", "given": "Yong Song", "initials": "YS"}, {"family": "Nilsson", "given": "Jonas Andreas", "initials": "JA"}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J"}], "type": "journal-article", "published": "2019-12-01", "journal": {"volume": "8", "issn": "2001-3078", "issue": "1", "pages": "1650458", "title": "J Extracell Vesicles", "issn-l": "2001-3078"}, "abstract": "Extracellular vesicles such as exosomes convey biological messages between cells, either by surface-to-surface interaction or by shuttling of bioactive molecules to a recipient cell's cytoplasm. Here we show that exosomes released by mast cells harbour both active and latent transforming growth factor \u03b2-1 (TGF\u03b2-1) on their surfaces. The latent form of TGF\u03b2-1 is associated with the exosomes via heparinase-II and pH-sensitive elements. These vesicles traffic to the endocytic compartment of recipient human mesenchymal stem cells (MSCs) within 60 min of exposure. Further, the exosomes-associated TGF\u03b2-1 is retained within the endosomal compartments at the time of signalling, which results in prolonged cellular signalling compared to free-TGF\u03b2-1. These exosomes induce a migratory phenotype in primary MSCs involving SMAD-dependent pathways. Our results show that mast cell-derived exosomes are decorated with latent TGF\u03b2-1 and are retained in recipient MSC endosomes, influencing recipient cell migratory phenotype. We conclude that exosomes can convey signalling within endosomes by delivering bioactive surface ligands to this intracellular compartment.", "doi": "10.1080/20013078.2019.1650458", "pmid": "31595182", "labels": {"Integrated Microscopy Technologies Stockholm": null, "Integrated Microscopy Technologies Gothenburg": "Service", "Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [], "notes": [], "created": "2020-01-23T16:12:44.449Z", "modified": "2024-01-16T13:46:31.140Z"}, {"entity": "publication", "iuid": "c5320b00cf0741ca95e0c5e91858b2aa", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c5320b00cf0741ca95e0c5e91858b2aa.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c5320b00cf0741ca95e0c5e91858b2aa"}}, "title": "The MTH1 inhibitor TH588 is a microtubule-modulating agent that eliminates cancer cells by activating the mitotic surveillance pathway", "authors": [{"family": "Gul", "given": "Nadia", "initials": "N"}, {"family": "Karlsson", "given": "Joakim", "initials": "J", "orcid": "0000-0001-6332-4043", "researcher": {"href": "https://publications.scilifelab.se/researcher/6190c1a8a7d54cd6807f120e8748cfcd.json"}}, {"family": "T\u00e4ngemo", "given": "Carolina", "initials": "C"}, {"family": "Linsefors", "given": "Sanna", "initials": "S"}, {"family": "Tuyizere", "given": "Samuel", "initials": "S"}, {"family": "Perkins", "given": "Rosie", "initials": "R"}, {"family": "Ala", "given": "Chandu", "initials": "C"}, {"family": "Zou", "given": "Zhiyuan", "initials": "Z"}, {"family": "Larsson", "given": "Erik", "initials": "E"}, {"family": "Berg\u00f6", "given": "Martin O", "initials": "MO"}, {"family": "Lindahl", "given": "Per", "initials": "P"}], "type": "journal-article", "published": "2019-12-00", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "9", "issue": "1", "pages": "14667", "issn-l": "2045-2322"}, "abstract": "The mut-T homolog-1 (MTH1) inhibitor TH588 has shown promise in preclinical cancer studies but its targeting specificity has been questioned. Alternative mechanisms for the anti-cancer effects of TH588 have been suggested but the question remains unresolved. Here, we performed an unbiased CRISPR screen on human lung cancer cells to identify potential mechanisms behind the cytotoxic effect of TH588. The screen identified pathways and complexes involved in mitotic spindle regulation. Using immunofluorescence and live cell imaging, we showed that TH588 rapidly reduced microtubule plus-end mobility, disrupted mitotic spindles, and prolonged mitosis in a concentration-dependent but MTH1-independent manner. These effects activated a USP28-p53 pathway - the mitotic surveillance pathway - that blocked cell cycle reentry after prolonged mitosis; USP28 acted upstream of p53 to arrest TH588-treated cells in the G1-phase of the cell cycle. We conclude that TH588 is a microtubule-modulating agent that activates the mitotic surveillance pathway and thus prevents cancer cells from re-entering the cell cycle.", "doi": "10.1038/s41598-019-51205-w", "pmid": "31604991", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-019-51205-w"}, {"db": "pmc", "key": "PMC6789014"}], "notes": [], "created": "2020-01-23T16:02:13.461Z", "modified": "2021-06-16T14:42:57.467Z"}, {"entity": "publication", "iuid": "9bb120725da54b6cb3462b0c299b134f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9bb120725da54b6cb3462b0c299b134f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9bb120725da54b6cb3462b0c299b134f"}}, "title": "Structural weakening of the colonic mucus barrier is an early event in ulcerative colitis pathogenesis.", "authors": [{"family": "van der Post", "given": "Sjoerd", "initials": "S"}, {"family": "Jabbar", "given": "Karolina S", "initials": "KS"}, {"family": "Birchenough", "given": "George", "initials": "G"}, {"family": "Arike", "given": "Liisa", "initials": "L"}, {"family": "Akhtar", "given": "Noreen", "initials": "N"}, {"family": "Sjovall", "given": "Henrik", "initials": "H"}, {"family": "Johansson", "given": "Malin E V", "initials": "MEV"}, {"family": "Hansson", "given": "Gunnar C", "initials": "GC", "orcid": "0000-0002-1900-1869", "researcher": {"href": "https://publications.scilifelab.se/researcher/44b3815603154322a6dac16f2fc1c1e9.json"}}], "type": "journal article", "published": "2019-12-00", "journal": {"title": "Gut", "issn": "1468-3288", "volume": "68", "issue": "12", "pages": "2142-2151", "issn-l": "0017-5749"}, "abstract": "The colonic inner mucus layer protects us from pathogens and commensal-induced inflammation, and has been shown to be defective in active UC. The aim of this study was to determine the underlying compositional alterations, their molecular background and potential contribution to UC pathogenesis.\n\nIn this single-centre case-control study, sigmoid colon biopsies were obtained from patients with UC with ongoing inflammation (n=36) or in remission (n=28), and from 47 patients without colonic disease. Mucus samples were collected from biopsies ex vivo, and their protein composition analysed by nanoliquid chromatography-tandem mass spectrometry. Mucus penetrability and goblet cell responses to microbial stimulus were assessed in a subset of patients.\n\nThe core mucus proteome was found to consist of a small set of 29 secreted/transmembrane proteins. In active UC, major structural mucus components including the mucin MUC2 (p<0.0001) were reduced, also in non-inflamed segments. Active UC was associated with decreased numbers of sentinel goblet cells and attenuation of the goblet cell secretory response to microbial challenge. Abnormal penetrability of the inner mucus layer was observed in a subset of patients with UC (12/40; 30%). Proteomic alterations in penetrable mucus samples included a reduction of the SLC26A3 apical membrane anion exchanger, which supplies bicarbonate required for colonic mucin barrier formation.\n\nCore mucus structural components were reduced in active UC. These alterations were associated with attenuation of the goblet cell secretory response to microbial challenge, but occurred independent of local inflammation. Thus, mucus abnormalities are likely to contribute to UC pathogenesis.", "doi": "10.1136/gutjnl-2018-317571", "pmid": "30914450", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "gutjnl-2018-317571"}, {"db": "pmc", "key": "PMC6872445"}], "notes": [], "created": "2020-01-23T16:13:52.632Z", "modified": "2021-06-16T14:45:18.142Z"}, {"entity": "publication", "iuid": "ea5f24f5fbcb42c6b7012e20724fe78f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ea5f24f5fbcb42c6b7012e20724fe78f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ea5f24f5fbcb42c6b7012e20724fe78f"}}, "title": "Calcium-activated chloride channel regulator 1 (CLCA1) forms non-covalent oligomers in colonic mucus and has mucin 2-processing properties.", "authors": [{"family": "Nystr\u00f6m", "given": "Elisabeth E L", "initials": "EEL", "orcid": "0000-0002-6970-7894", "researcher": {"href": "https://publications.scilifelab.se/researcher/09bd302f8a1341f6a1a5aaf3bfe94a94.json"}}, {"family": "Arike", "given": "Liisa", "initials": "L"}, {"family": "Ehrencrona", "given": "Erik", "initials": "E"}, {"family": "Hansson", "given": "Gunnar C", "initials": "GC", "orcid": "0000-0002-1900-1869", "researcher": {"href": "https://publications.scilifelab.se/researcher/44b3815603154322a6dac16f2fc1c1e9.json"}}, {"family": "Johansson", "given": "Malin E V", "initials": "MEV", "orcid": "0000-0002-4237-6677", "researcher": {"href": "https://publications.scilifelab.se/researcher/520dab35c19049c8b3f1083a92e60d56.json"}}], "type": "journal article", "published": "2019-11-08", "journal": {"title": "J. Biol. Chem.", "issn": "1083-351X", "volume": "294", "issue": "45", "pages": "17075-17089", "issn-l": "0021-9258"}, "abstract": "Calcium-activated chloride channel regulator 1 (CLCA1) is one of the major nonmucin proteins found in intestinal mucus. It is part of a larger family of CLCA proteins that share highly conserved features and domain architectures. The CLCA domain arrangement is similar to proteins belonging to the ADAM (a disintegrin and metalloproteinase) family, known to process extracellular matrix proteins. Therefore, CLCA1 is an interesting candidate in the search for proteases that process intestinal mucus. Here, we investigated CLCA1's biochemical properties both in vitro and in mucus from mouse and human colon biopsy samples. Using immunoblotting with CLCA1-specific antibodies and recombinant proteins, we observed that the CLCA1 C-terminal self-cleavage product forms a disulfide-linked dimer that noncovalently interacts with the N-terminal part of CLCA1, which further interacts to form oligomers. We also characterized a second, more catalytically active, N-terminal product of CLCA1, encompassing the catalytic domain together with its von Willebrand domain type A (VWA). This fragment was unstable but could be identified in freshly prepared mucus. Furthermore, we found that CLCA1 can cleave the N-terminal part of the mucus structural component MUC2. We propose that CLCA1 regulates the structural arrangement of the mucus and thereby takes part in the regulation of mucus processing.", "doi": "10.1074/jbc.RA119.009940", "pmid": "31570526", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S0021-9258(20)30545-7"}, {"db": "pmc", "key": "PMC6851300"}], "notes": [], "created": "2020-01-23T16:07:41.394Z", "modified": "2021-06-16T16:19:47.303Z"}, {"entity": "publication", "iuid": "6e423bae8c7141548aaf0589c8f8adf7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6e423bae8c7141548aaf0589c8f8adf7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6e423bae8c7141548aaf0589c8f8adf7"}}, "title": "The Nlrp6 inflammasome is not required for baseline colonic inner mucus layer formation or function.", "authors": [{"family": "Volk", "given": "Joana K", "initials": "JK"}, {"family": "Nystr\u00f6m", "given": "Elisabeth E L", "initials": "EEL"}, {"family": "van der Post", "given": "Sjoerd", "initials": "S"}, {"family": "Abad", "given": "Beatriz M", "initials": "BM"}, {"family": "Schroeder", "given": "Bjoern O", "initials": "BO", "orcid": "0000-0002-6716-8284", "researcher": {"href": "https://publications.scilifelab.se/researcher/c2c57653fc214cbcbb242cbbc524d517.json"}}, {"family": "Johansson", "given": "\u00c5sa", "initials": "\u00c5"}, {"family": "Svensson", "given": "Frida", "initials": "F"}, {"family": "J\u00e4verfelt", "given": "Sofia", "initials": "S"}, {"family": "Johansson", "given": "Malin E V", "initials": "MEV", "orcid": "0000-0002-4237-6677", "researcher": {"href": "https://publications.scilifelab.se/researcher/520dab35c19049c8b3f1083a92e60d56.json"}}, {"family": "Hansson", "given": "Gunnar C", "initials": "GC", "orcid": "0000-0002-1900-1869", "researcher": {"href": "https://publications.scilifelab.se/researcher/44b3815603154322a6dac16f2fc1c1e9.json"}}, {"family": "Birchenough", "given": "George M H", "initials": "GMH", "orcid": "0000-0003-2283-2353", "researcher": {"href": "https://publications.scilifelab.se/researcher/aecb4d51bffc490d87b0a4fffb7de59a.json"}}], "type": "journal article", "published": "2019-11-04", "journal": {"title": "J. Exp. Med.", "issn": "1540-9538", "volume": "216", "issue": "11", "pages": "2602-2618", "issn-l": "0022-1007"}, "abstract": "The inner mucus layer (IML) is a critical barrier that protects the colonic epithelium from luminal threats and inflammatory bowel disease. Innate immune signaling is thought to regulate IML formation via goblet cell Nlrp6 inflammasome activity that controls secretion of the mucus structural component Muc2. We report that isolated colonic goblet cells express components of several inflammasomes; however, analysis of IML properties in multiple inflammasome-deficient mice, including littermate-controlled Nlrp6 , detect a functional IML barrier in all strains. Analysis of mice lacking inflammasome substrate cytokines identifies a defective IML in -/-Il18 mice, but this phenotype is ultimately traced to a microbiota-driven, Il18-independent effect. Analysis of phenotypic transfer between IML-deficient and IML-intact mice finds that the Bacteroidales family S24-7 (Muribaculaceae) and genus -/-Adlercrutzia consistently positively covary with IML barrier function. Together, our results demonstrate that baseline IML formation and function is independent of inflammasome activity and highlights the role of the microbiota in determining IML barrier function.", "doi": "10.1084/jem.20190679", "pmid": "31420376", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "jem.20190679"}, {"db": "pmc", "key": "PMC6829596"}], "notes": [], "created": "2020-01-23T16:14:20.940Z", "modified": "2021-06-16T16:20:41.684Z"}, {"entity": "publication", "iuid": "c660cde368f44843955c0744bec27b03", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c660cde368f44843955c0744bec27b03.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c660cde368f44843955c0744bec27b03"}}, "title": "Challenges for CLEM from a Light Microscopy Perspective", "authors": [{"family": "Anderson", "given": "Kurt", "initials": "K"}, {"family": "Nilsson", "given": "Tommy", "initials": "T"}, {"family": "Fernandez\u2010Rodriguez", "given": "Julia", "initials": "J"}], "type": "other", "published": "2019-10-15", "journal": {"title": "John Wiley & Sons Ltd", "issn": null, "issn-l": null, "volume": "2", "issue": null, "pages": "23-35"}, "abstract": null, "doi": "10.1002/9781119086420.ch2", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2020-01-23T15:55:07.485Z", "modified": "2021-06-21T14:44:05.301Z"}, {"entity": "publication", "iuid": "d5b820ef1ecb4e649af639d9aba5a970", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d5b820ef1ecb4e649af639d9aba5a970.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d5b820ef1ecb4e649af639d9aba5a970"}}, "title": "A Fluorescent Kinase Inhibitor that Exhibits Diagnostic Changes in Emission upon Binding.", "authors": [{"family": "Fleming", "given": "Cassandra L", "initials": "CL", "orcid": "0000-0002-7730-7305", "researcher": {"href": "https://publications.scilifelab.se/researcher/a29a83ba2b3444768821489dc667279e.json"}}, {"family": "Sandoz", "given": "Patrick A", "initials": "PA", "orcid": "0000-0002-8379-7267", "researcher": {"href": "https://publications.scilifelab.se/researcher/acd737132e4b4b378257ae8f0316b3a2.json"}}, {"family": "Inghardt", "given": "Tord", "initials": "T", "orcid": "0000-0002-4804-9474", "researcher": {"href": "https://publications.scilifelab.se/researcher/bc8a41790a034fe48cce02c8e7034e34.json"}}, {"family": "\u00d6nfelt", "given": "Bj\u00f6rn", "initials": "B", "orcid": "0000-0001-5178-7593", "researcher": {"href": "https://publications.scilifelab.se/researcher/14bcdcf94cab40ff92319869d243f5d8.json"}}, {"family": "Gr\u00f8tli", "given": "Morten", "initials": "M", "orcid": "0000-0003-3621-4222", "researcher": {"href": "https://publications.scilifelab.se/researcher/764706606bcb4afba1150af332c0f124.json"}}, {"family": "Andr\u00e9asson", "given": "Joakim", "initials": "J", "orcid": "0000-0003-4695-7943", "researcher": {"href": "https://publications.scilifelab.se/researcher/28eb5affb5664c54be9171dfce6bea15.json"}}], "type": "journal article", "published": "2019-10-14", "journal": {"title": "Angew. Chem. Int. Ed. Engl.", "issn": "1521-3773", "volume": "58", "issue": "42", "pages": "15000-15004", "issn-l": "1433-7851"}, "abstract": "The development of a fluorescent LCK inhibitor that exhibits favourable solvatochromic properties upon binding the kinase is described. Fluorescent properties were realised through the inclusion of a prodan-derived fluorophore into the pharmacophore of an ATP-competitive kinase inhibitor. Fluorescence titration experiments demonstrate the solvatochromic properties of the inhibitor, in which dramatic increase in emission intensity and hypsochromic shift in emission maxima are clearly observed upon binding LCK. Microscopy experiments in cellular contexts together with flow cytometry show that the fluorescence intensity of the inhibitor correlates with the LCK concentration. Furthermore, multiphoton microscopy experiments demonstrate both the rapid cellular uptake of the inhibitor and that the two-photon cross section of the inhibitor is amenable for excitation at 700 nm.", "doi": "10.1002/anie.201909536", "pmid": "31411364", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC6851755"}], "notes": [], "created": "2020-01-23T16:40:34.671Z", "modified": "2021-06-18T13:56:45.251Z"}, {"entity": "publication", "iuid": "b79b811e9f0642fd9f549d71ee492460", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b79b811e9f0642fd9f549d71ee492460.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b79b811e9f0642fd9f549d71ee492460"}}, "title": "Nestin Regulates Neurogenesis in Mice Through Notch Signaling From Astrocytes to Neural Stem Cells.", "authors": [{"family": "Wilhelmsson", "given": "Ulrika", "initials": "U"}, {"family": "Lebkuechner", "given": "Isabell", "initials": "I"}, {"family": "Leke", "given": "Renata", "initials": "R"}, {"family": "Marasek", "given": "Pavel", "initials": "P"}, {"family": "Yang", "given": "Xiaoguang", "initials": "X"}, {"family": "Antfolk", "given": "Daniel", "initials": "D"}, {"family": "Chen", "given": "Meng", "initials": "M"}, {"family": "Mohseni", "given": "Paria", "initials": "P"}, {"family": "Lasi\u010d", "given": "Eva", "initials": "E"}, {"family": "Bobnar", "given": "Sa\u0161a Trkov", "initials": "ST"}, {"family": "Stenovec", "given": "Matja\u017e", "initials": "M"}, {"family": "Zorec", "given": "Robert", "initials": "R"}, {"family": "Nagy", "given": "Andras", "initials": "A"}, {"family": "Sahlgren", "given": "Cecilia", "initials": "C"}, {"family": "Pekna", "given": "Marcela", "initials": "M"}, {"family": "Pekny", "given": "Milos", "initials": "M"}], "type": "journal article", "published": "2019-09-13", "journal": {"title": "Cereb. Cortex", "issn": "1460-2199", "volume": "29", "issue": "10", "pages": "4050-4066", "issn-l": "1047-3211"}, "abstract": "The intermediate filament (nanofilament) protein nestin is a marker of neural stem cells, but its role in neurogenesis, including adult neurogenesis, remains unclear. Here, we investigated the role of nestin in neurogenesis in adult nestin-deficient (Nes-/-) mice. We found that the proliferation of Nes-/- neural stem cells was not altered, but neurogenesis in the hippocampal dentate gyrus of Nes-/- mice was increased. Surprisingly, the proneurogenic effect of nestin deficiency was mediated by its function in the astrocyte niche. Through its role in Notch signaling from astrocytes to neural stem cells, nestin negatively regulates neuronal differentiation and survival; however, its expression in neural stem cells is not required for normal neurogenesis. In behavioral studies, nestin deficiency in mice did not affect associative learning but was associated with impaired long-term memory.", "doi": "10.1093/cercor/bhy284", "pmid": "30605503", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "5263979"}], "notes": [], "created": "2020-01-23T16:15:12.816Z", "modified": "2021-06-18T14:08:06.008Z"}, {"entity": "publication", "iuid": "7150d6319b854b92b8297e7737519205", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7150d6319b854b92b8297e7737519205.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7150d6319b854b92b8297e7737519205"}}, "title": "Vimentin Phosphorylation Is Required for Normal Cell Division of Immature Astrocytes.", "authors": [{"family": "de Pablo", "given": "Yolanda", "initials": "Y"}, {"family": "Marasek", "given": "Pavel", "initials": "P"}, {"family": "Pozo-Rodrig\u00e1lvarez", "given": "Andrea", "initials": "A"}, {"family": "Wilhelmsson", "given": "Ulrika", "initials": "U"}, {"family": "Inagaki", "given": "Masaki", "initials": "M"}, {"family": "Pekna", "given": "Marcela", "initials": "M"}, {"family": "Pekny", "given": "Milos", "initials": "M"}], "type": "journal article", "published": "2019-09-01", "journal": {"title": "Cells", "issn": "2073-4409", "volume": "8", "issue": "9", "pages": "1016", "issn-l": "2073-4409"}, "abstract": "Vimentin (VIM) is an intermediate filament (nanofilament) protein expressed in multiple cell types, including astrocytes. Mice with VIM mutations of serine sites phosphorylated during mitosis (VIMSA/SA) show cytokinetic failure in fibroblasts and lens epithelial cells, chromosomal instability, facilitated cell senescence, and increased neuronal differentiation of neural progenitor cells. Here we report that in vitro immature VIMSA/SA astrocytes exhibit cytokinetic failure and contain vimentin accumulations that co-localize with mitochondria. This phenotype is transient and disappears with VIMSA/SA astrocyte maturation and expression of glial fibrillary acidic protein (GFAP); it is also alleviated by the inhibition of cell proliferation. To test the hypothesis that GFAP compensates for the effect of VIMSA/SA in astrocytes, we crossed the VIMSA/SA and GFAP-/- mice. Surprisingly, the fraction of VIMSA/SA immature astrocytes with abundant vimentin accumulations was reduced when on GFAP-/- background. This indicates that the disappearance of vimentin accumulations and cytokinetic failure in mature astrocyte cultures are independent of GFAP expression. Both VIMSA/SA and VIMSA/SAGFAP-/- astrocytes showed normal mitochondrial membrane potential and vulnerability to H2O2, oxygen/glucose deprivation, and chemical ischemia. Thus, mutation of mitotic phosphorylation sites in vimentin triggers formation of vimentin accumulations and cytokinetic failure in immature astrocytes without altering their vulnerability to oxidative stress.", "doi": "10.3390/cells8091016", "pmid": "31480524", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "cells8091016"}, {"db": "pmc", "key": "PMC6769829"}], "notes": [], "created": "2020-01-23T16:01:26.707Z", "modified": "2021-06-18T14:09:27.564Z"}, {"entity": "publication", "iuid": "672b919f2bc14c02a161b8e63b499eb3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/672b919f2bc14c02a161b8e63b499eb3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/672b919f2bc14c02a161b8e63b499eb3"}}, "title": "Perturbed ovarian and uterine glucocorticoid receptor signaling accompanies the balanced regulation of mitochondrial function and NF\u03baB-mediated inflammation under conditions of hyperandrogenism and insulin resistance.", "authors": [{"family": "Hu", "given": "Min", "initials": "M"}, {"family": "Zhang", "given": "Yuehui", "initials": "Y"}, {"family": "Guo", "given": "Xiaozhu", "initials": "X"}, {"family": "Jia", "given": "Wenyan", "initials": "W"}, {"family": "Liu", "given": "Guoqi", "initials": "G"}, {"family": "Zhang", "given": "Jiao", "initials": "J"}, {"family": "Cui", "given": "Peng", "initials": "P"}, {"family": "Li", "given": "Juan", "initials": "J"}, {"family": "Li", "given": "Wei", "initials": "W"}, {"family": "Wu", "given": "Xiaoke", "initials": "X"}, {"family": "Ma", "given": "Hongxia", "initials": "H"}, {"family": "Br\u00e4nnstr\u00f6m", "given": "Mats", "initials": "M"}, {"family": "Shao", "given": "Linus R", "initials": "LR"}, {"family": "Billig", "given": "H\u00e5kan", "initials": "H"}], "type": "journal article", "published": "2019-09-01", "journal": {"title": "Life Sciences", "issn": "1879-0631", "volume": "232", "issue": null, "pages": "116681", "issn-l": "0024-3205"}, "abstract": "This study aimed to determine whether glucocorticoid receptor (GR) signaling, mitochondrial function, and local inflammation in the ovary and uterus are intrinsically different in rats with hyperandrogenism and insulin resistance compared to controls.\n\nFemale Sprague Dawley rats were exposed to daily injections of human chorionic gonadotropin and/or insulin.\n\nIn both the ovary and the uterus, decreased expression of the two GR isoforms was concurrent with increased expression of Fkbp51 but not Fkbp52 mRNA in hCG + insulin-treated rats. However, these rats exhibited contrasting regulation of Hsd11b1 and Hsd11b2 mRNAs in the two tissues. Further, the expression of several oxidative phosphorylation-related proteins decreased in the ovary and uterus following hCG and insulin stimulation, in contrast to increased expression of many genes involved in mitochondrial function and homeostasis. Additionally, hCG + insulin-treated rats showed increased expression of ovarian and uterine NF\u03baB signaling proteins and Tnfaip3 mRNA. The mRNA expression of Il1b, Il6, and Mmp2 was decreased in both tissues, while the mRNA expression of Tnfa, Ccl2, Ccl5, and Mmp3 was increased in the uterus. Ovaries and uteri from animals co-treated with hCG and insulin showed increased collagen deposition compared to controls.\n\nOur observations suggest that hyperandrogenism and insulin resistance disrupt ovarian and uterine GR activation and trigger compensatory or adaptive effects for mitochondrial homeostasis, allowing tissue-level maintenance of mitochondrial function in order to limit ovarian and uterine dysfunction. Our study also suggests that hyperandrogenism and insulin resistance activate NF\u03baB signaling resulting in aberrant regulation of inflammation-related gene expression.", "doi": "10.1016/j.lfs.2019.116681", "pmid": "31344428", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S0024-3205(19)30607-1"}], "notes": [], "created": "2020-01-23T16:02:56.216Z", "modified": "2021-06-18T14:10:20.962Z"}, {"entity": "publication", "iuid": "283a394561d1464badcf897ff572100c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/283a394561d1464badcf897ff572100c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/283a394561d1464badcf897ff572100c"}}, "title": "DNA analysis of low- and high-density fractions defines heterogeneous subpopulations of small extracellular vesicles based on their DNA cargo and topology.", "authors": [{"family": "L\u00e1zaro-Ib\u00e1\u00f1ez", "given": "Elisa", "initials": "E"}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C"}, {"family": "Shelke", "given": "Ganesh Vilas", "initials": "GV"}, {"family": "Crescitelli", "given": "Rossella", "initials": "R"}, {"family": "Jang", "given": "Su Chul", "initials": "SC"}, {"family": "Cvjetkovic", "given": "Aleksander", "initials": "A"}, {"family": "Garc\u00eda-Rodr\u00edguez", "given": "Ana\u00eds", "initials": "A"}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J"}], "type": "journal article", "published": "2019-08-27", "journal": {"volume": "8", "issn": "2001-3078", "issue": "1", "pages": "1656993", "title": "J Extracell Vesicles", "issn-l": "2001-3078"}, "abstract": "Extracellular vesicles have the capacity to transfer lipids, proteins, and nucleic acids between cells, thereby influencing the recipient cell's phenotype. While the role of RNAs in EVs has been extensively studied, the function of DNA remains elusive. Here, we distinguished novel heterogeneous subpopulations of small extracellular vesicles (sEVs) based on their DNA content and topology. Low- and high-density sEV subsets from a human mast cell line (HMC-1) and an erythroleukemic cell line (TF-1) were separated using high-resolution iodixanol density gradients to discriminate the nature of the DNA cargo of the sEVs. Paired comparisons of the sEV-associated DNA and RNA molecules showed that RNA was more abundant than DNA and that most of the DNA was present in the high-density fractions, demonstrating that sEV subpopulations have different DNA content. DNA was predominately localised on the outside or surface of sEVs, with only a small portion being protected from enzymatic degradation. Whole-genome sequencing identified DNA fragments spanning all chromosomes and mitochondrial DNA when sEVs were analysed in bulk. Our work contributes to the understanding of how DNA is associated with sEVs and thus provides direction for distinguishing subtypes of EVs based on their DNA cargo and topology.", "doi": "10.1080/20013078.2019.1656993", "pmid": "31497265", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "1656993"}, {"db": "pmc", "key": "PMC6719264"}], "notes": [], "created": "2019-12-02T17:20:34.874Z", "modified": "2021-05-24T15:37:29.263Z"}, {"entity": "publication", "iuid": "e35d48e8ac824c1998c799a407674a4b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e35d48e8ac824c1998c799a407674a4b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e35d48e8ac824c1998c799a407674a4b"}}, "title": "The human transmembrane mucin MUC17 responds to TNF\u03b1 by increased presentation at the plasma membrane.", "authors": [{"family": "Schneider", "given": "Hannah", "initials": "H"}, {"family": "Berger", "given": "Evelin", "initials": "E"}, {"family": "Dolan", "given": "Brendan", "initials": "B"}, {"family": "Martinez-Abad", "given": "Beatriz", "initials": "B"}, {"family": "Arike", "given": "Liisa", "initials": "L"}, {"family": "Pelaseyed", "given": "Thaher", "initials": "T", "orcid": "0000-0002-6434-3913", "researcher": {"href": "https://publications.scilifelab.se/researcher/9dc0aa3d9762420caa7efaaa19c1174b.json"}}, {"family": "Hansson", "given": "Gunnar C", "initials": "GC", "orcid": "0000-0002-1900-1869", "researcher": {"href": "https://publications.scilifelab.se/researcher/44b3815603154322a6dac16f2fc1c1e9.json"}}], "type": "journal article", "published": "2019-08-22", "journal": {"title": "Biochem. J.", "issn": "1470-8728", "volume": "476", "issue": "16", "pages": "2281-2295", "issn-l": "0264-6021"}, "abstract": "Transmembrane mucin MUC17 is an integral part of the glycocalyx as it covers the brush border membrane of small intestinal enterocytes and presents an extended O-glycosylated mucin domain to the intestinal lumen. Here, we identified two unknown phosphorylated serine residues, S4428 and S4492, in the cytoplasmic tail of human MUC17. We have previously demonstrated that MUC17 is anchored to the apical membrane domain via an interaction with the scaffolding protein PDZK1. S4492, localized in the C-terminal PDZ binding motif of MUC17, was mutated to generate phosphomimetic and phosphodeficient variants of MUC17. Using Caco-2 cells as a model system, we found that induction of an inflammatory state by long-term stimulation with the proinflammatory cytokine TNF\u03b1 resulted in an increase of MUC17 protein levels and enhanced insertion of MUC17 and its two phospho-variants into apical membranes. Up-regulation and apical insertion of MUC17 was followed by shedding of MUC17-containing vesicles. Transmembrane mucins have previously been shown to play a role in the prevention of bacterial colonization by acting as sheddable decoys for encroaching bacteria. Overexpression and increased presentation at the plasma membrane of wild-type MUC17 and its phosphodeficient variant MUC17 S-4492A protected Caco-2 cells against adhesion of enteropathogenic Escherichia coli, indicating that C-terminal phosphorylation of MUC17 may play a functional role in epithelial cell protection. We propose a new function for MUC17 in inflammation, where MUC17 acts as a second line of defense by preventing attachment of bacteria to the epithelial cell glycocalyx in the small intestine.", "doi": "10.1042/BCJ20190180", "pmid": "31387973", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "BCJ20190180"}, {"db": "pmc", "key": "PMC6705488"}], "notes": [], "created": "2020-01-23T16:13:08.991Z", "modified": "2021-06-18T14:11:11.815Z"}, {"entity": "publication", "iuid": "e1779e0f144b4e769f07103efdfd4aee", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e1779e0f144b4e769f07103efdfd4aee.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e1779e0f144b4e769f07103efdfd4aee"}}, "title": "Syntaxin 5 Is Required for the Formation and Clearance of Protein Inclusions during Proteostatic Stress.", "authors": [{"family": "Babazadeh", "given": "Roja", "initials": "R"}, {"family": "Ahmadpour", "given": "Doryaneh", "initials": "D"}, {"family": "Jia", "given": "Song", "initials": "S"}, {"family": "Hao", "given": "Xinxin", "initials": "X"}, {"family": "Widlund", "given": "Per", "initials": "P"}, {"family": "Schneider", "given": "Kara", "initials": "K"}, {"family": "Eisele", "given": "Frederik", "initials": "F"}, {"family": "Edo", "given": "Laura Dolz", "initials": "LD"}, {"family": "Smits", "given": "Gertien J", "initials": "GJ"}, {"family": "Liu", "given": "Beidong", "initials": "B"}, {"family": "Nystrom", "given": "Thomas", "initials": "T"}], "type": "journal article", "published": "2019-08-20", "journal": {"title": "Cell Rep", "issn": "2211-1247", "volume": "28", "issue": "8", "pages": "2096-2110.e8", "issn-l": null}, "abstract": "Spatial sorting to discrete quality control sites in the cell is a process harnessing the toxicity of aberrant proteins. We show that the yeast t-snare phosphoprotein syntaxin5 (Sed5) acts as a key factor in mitigating proteotoxicity and the spatial deposition and clearance of IPOD (insoluble protein deposit) inclusions associates with the disaggregase Hsp104. Sed5 phosphorylation promotes dynamic movement of COPII-associated Hsp104 and boosts disaggregation by favoring anterograde ER-to-Golgi trafficking. Hsp104-associated aggregates co-localize with Sed5 as well as components of the ER, trans Golgi network, and endocytic vesicles, transiently during proteostatic stress, explaining mechanistically how misfolded and aggregated proteins formed at the vicinity of the ER can hitchhike toward vacuolar IPOD sites. Many inclusions become associated with mitochondria in a HOPS/vCLAMP-dependent manner and co-localize with Vps39 (HOPS/vCLAMP) and Vps13, which are proteins providing contacts between vacuole and mitochondria. Both Vps39 and Vps13 are required also for efficient Sed5-dependent clearance of aggregates.", "doi": "10.1016/j.celrep.2019.07.053", "pmid": "31433985", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S2211-1247(19)30957-X"}], "notes": [], "created": "2020-01-23T15:59:41.811Z", "modified": "2023-06-19T13:02:31.708Z"}, {"entity": "publication", "iuid": "4461bb69c8ea443193eb31bbee80e195", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4461bb69c8ea443193eb31bbee80e195.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4461bb69c8ea443193eb31bbee80e195"}}, "title": "Mesenchymal stromal cell-derived nanovesicles ameliorate bacterial outer membrane vesicle-induced sepsis via IL-10.", "authors": [{"family": "Park", "given": "Kyong-Su", "initials": "KS", "orcid": "0000-0003-0902-7800", "researcher": {"href": "https://publications.scilifelab.se/researcher/26e308b29fe144b49f4db27f4b819c18.json"}}, {"family": "Svennerholm", "given": "Kristina", "initials": "K"}, {"family": "Shelke", "given": "Ganesh V", "initials": "GV"}, {"family": "Bandeira", "given": "Elga", "initials": "E"}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C"}, {"family": "Jang", "given": "Su Chul", "initials": "SC"}, {"family": "Chandode", "given": "Rakesh", "initials": "R"}, {"family": "Gribonika", "given": "Inta", "initials": "I"}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J"}], "type": "journal article", "published": "2019-08-01", "journal": {"title": "Stem Cell Res Ther", "issn": "1757-6512", "volume": "10", "issue": "1", "pages": "231", "issn-l": "1757-6512"}, "abstract": "Sepsis remains a source of high mortality in hospitalized patients despite proper antibiotic approaches. Encouragingly, mesenchymal stromal cells (MSCs) and their produced extracellular vesicles (EVs) have been shown to elicit anti-inflammatory effects in multiple inflammatory conditions including sepsis. However, EVs are generally released from mammalian cells in relatively low amounts, and high-yield isolation of EVs is still challenging due to a complicated procedure. To get over these limitations, vesicles very similar to EVs can be produced by serial extrusions of cells, after which they are called nanovesicles (NVs). We hypothesized that MSC-derived NVs can attenuate the cytokine storm induced by bacterial outer membrane vesicles (OMVs) in mice, and we aimed to elucidate the mechanism involved.\n\nNVs were produced from MSCs by the breakdown of cells through serial extrusions and were subsequently floated in a density gradient. Morphology and the number of NVs were analyzed by transmission electron microscopy and nanoparticle tracking analysis. Mice were intraperitoneally injected with Escherichia coli-derived OMVs to establish sepsis, and then injected with 2 \u00d7 10 9 NVs. Innate inflammation was assessed in peritoneal fluid and blood through investigation of infiltration of cells and cytokine production. The biodistribution of NVs labeled with Cy7 dye was analyzed using near-infrared imaging.\n\nElectron microscopy showed that NVs have a nanometer-size spherical shape and harbor classical EV marker proteins. In mice, NVs inhibited eye exudates and hypothermia, signs of a systemic cytokine storm, induced by intraperitoneal injection of OMVs. Moreover, NVs significantly suppressed cytokine release into the systemic circulation, as well as neutrophil and monocyte infiltration in the peritoneum. The protective effect of NVs was significantly reduced by prior treatment with anti-interleukin (IL)-10 monoclonal antibody. In biodistribution study, NVs spread to the whole mouse body and localized in the lung, liver, and kidney at 6 h.\n\nTaken together, these data indicate that MSC-derived NVs have beneficial effects in a mouse model of sepsis by upregulating the IL-10 production, suggesting that artificial NVs may be novel EV-mimetics clinically applicable to septic patients.", "doi": "10.1186/s13287-019-1352-4", "pmid": "31370884", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "10.1186/s13287-019-1352-4"}, {"db": "pmc", "key": "PMC6676541"}], "notes": [], "created": "2020-01-23T16:10:40.078Z", "modified": "2021-06-16T14:54:54.314Z"}, {"entity": "publication", "iuid": "0a1c09ce937f4dec80520426eb0d6cf3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0a1c09ce937f4dec80520426eb0d6cf3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0a1c09ce937f4dec80520426eb0d6cf3"}}, "title": "Mixture toxicity effects and uptake of titanium dioxide (TiO 2) nanoparticles and 3,3',4,4'-tetrachlorobiphenyl (PCB77) in juvenile brown trout following co-exposure via the diet.", "authors": [{"family": "Lammel", "given": "Tobias", "initials": "T"}, {"family": "Wassmur", "given": "Britt", "initials": "B"}, {"family": "Mackevica", "given": "Aiga", "initials": "A"}, {"family": "Chen", "given": "Chang-Er L", "initials": "CL"}, {"family": "Sturve", "given": "Joachim", "initials": "J"}], "type": "journal article", "published": "2019-08-00", "journal": {"volume": "213", "issn": "1879-1514", "issue": null, "pages": "105195", "title": "Aquat. Toxicol.", "issn-l": "0166-445X"}, "abstract": "Titanium dioxide nanoparticles (n-TiO 2) are among the man-made nanomaterials that are predicted to be found at high concentrations in the aquatic environment. There, they likely co-exist with other chemical pollutants. Thus, n-TiO2 and other chemical pollutants can be taken up together or accumulate independently from each other in prey organisms of fish. This can lead to dietary exposure of fish to n-TiO2-chemical pollutant mixtures. In this study, we examine if simultaneous dietary exposure to n-TiO2 and 3,3',4,4'-Tetrachlorobiphenyl (PCB77) -used as a model compound for persistent organic pollutants with dioxin-like properties- can influence the uptake and toxicological response elicited by the respective other substance. Juvenile brown trout (Salmo trutta) were fed custom-made food pellets containing n-TiO2, PCB77 or n-TiO2+PCB77 mixtures for 15 days. Ti and PCB77 concentrations in the liver were measured by ICP-MS and GC-MS, respectively. Besides, n-TiO2 uptake was assessed using TEM. Combination effects on endpoints specific for PCB77 (i.e., cytochrome P450 1A (CYP1A) induction) and endpoints shared by both PCB77 and n-TiO2 (i.e., oxidative stress-related parameters) were measured in intestine and liver using RT-qPCR and enzyme activity assays. The results show that genes encoding for proteins/enzymes essential for tight junction function (zo-1) and ROS elimination (sod-1) were significantly upregulated in the intestine of fish exposed to n-TiO2 and PCB77 mixtures, but not in the single-substance treatments. Besides, n-TiO2 had a potentiating effect on PCB77-induced CYP1A and glutathione reductase (GR) expression/enzyme activity in the liver. This study shows that simultaneous dietary exposure to nanomaterials and traditional environmental pollutants might result in effects that are larger than observed for the substances alone, but that understanding the mechanistic basis of such effects remains challenging.", "doi": "10.1016/j.aquatox.2019.04.021", "pmid": "31203167", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S0166-445X(18)31129-9"}], "notes": [], "created": "2020-01-23T16:04:26.739Z", "modified": "2021-06-18T14:15:14.819Z"}, {"entity": "publication", "iuid": "0b8e3f4e187a40cabc3ea6bad8e73999", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0b8e3f4e187a40cabc3ea6bad8e73999.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0b8e3f4e187a40cabc3ea6bad8e73999"}}, "title": "Choroid plexus transcriptome and ultrastructure analysis reveals a TLR2-specific chemotaxis signature and cytoskeleton remodeling in leukocyte trafficking.", "authors": [{"family": "Mottahedin", "given": "Amin", "initials": "A"}, {"family": "Joakim Ek", "given": "C", "initials": "C"}, {"family": "Truv\u00e9", "given": "Katarina", "initials": "K"}, {"family": "Hagberg", "given": "Henrik", "initials": "H"}, {"family": "Mallard", "given": "Carina", "initials": "C"}], "type": "journal article", "published": "2019-07-00", "journal": {"title": "Brain, Behavior, and Immunity", "issn": "1090-2139", "volume": "79", "issue": null, "pages": "216-227", "issn-l": "0889-1591"}, "abstract": "Perinatal infection and inflammation are major risk factors for injury in the developing brain, however, underlying mechanisms are not fully understood. Leukocyte migration to the cerebrospinal fluid (CSF) and brain is a hallmark of many pathologies of the central nervous system including those in neonates. We previously reported that systemic activation of Toll-like receptor (TLR) 2, a major receptor for gram-positive bacteria, by agonist Pam3CSK4 (P3C) resulted in dramatic neutrophil and monocyte infiltration to the CSF and periventricular brain of neonatal mice, an effect that was absent by the TLR4 agonist, LPS. Here we first report that choroid plexus is a route of TLR2-mediated leukocyte infiltration to the CSF by performing flow cytometry and transmission electron microscopy (TEM) of the choroid plexus. Next, we exploited the striking discrepancy between P3C and LPS effects on cell migration to determine the pathways regulating leukocyte trafficking through the choroid plexus. We performed RNA sequencing on the choroid plexus after administration of P3C and LPS to postnatal day 8 mice. A cluster gene analysis revealed a TLR2-specific signature of chemotaxis represented by 80-fold increased expression of the gene Ccl3 and 1000-fold increased expression of the gene Cxcl2. Ingenuity pathway analysis (IPA) revealed TLR2-specific molecular signaling related to cytoskeleton organization (e.g. actin signaling) as well as inositol phospholipids biosynthesis and degradation. This included upregulation of genes such as Rac2 and Micall2. In support of IPA results, ultrastructural analysis by TEM revealed clefting and perforations in the basement membrane of the choroid plexus epithelial cells in P3C-treated mice. In summary, we show that the choroid plexus is a route of TLR2-mediated transmigration of neutrophils and monocytes to the developing brain, and reveal previously unrecognized mechanisms that includes a specific chemotaxis profile as well as pathways regulating cytoskeleton and basement membrane remodeling.", "doi": "10.1016/j.bbi.2019.02.004", "pmid": "30822467", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S0889-1591(19)30142-4"}, {"db": "pmc", "key": "PMC6591031"}, {"db": "mid", "key": "NIHMS1523016"}], "notes": [], "created": "2020-01-23T16:09:43.913Z", "modified": "2021-06-21T09:55:47.355Z"}, {"entity": "publication", "iuid": "0d92142031ce4b088f4b6988fe5c283d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0d92142031ce4b088f4b6988fe5c283d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0d92142031ce4b088f4b6988fe5c283d"}}, "title": "BACH1 Stabilization by Antioxidants Stimulates Lung Cancer Metastasis", "authors": [{"family": "Wiel", "given": "Clotilde", "initials": "C"}, {"family": "Le Gal", "given": "Kristell", "initials": "K"}, {"family": "Ibrahim", "given": "Mohamed X", "initials": "MX"}, {"family": "Jahangir", "given": "Chowdhury Arif", "initials": "CA"}, {"family": "Kashif", "given": "Muhammad", "initials": "M"}, {"family": "Yao", "given": "Haidong", "initials": "H"}, {"family": "Ziegler", "given": "Dorian V", "initials": "DV"}, {"family": "Xu", "given": "Xiufeng", "initials": "X"}, {"family": "Ghosh", "given": "Tanushree", "initials": "T"}, {"family": "Mondal", "given": "Tanmoy", "initials": "T"}, {"family": "Kanduri", "given": "Chandrasekhar", "initials": "C"}, {"family": "Lindahl", "given": "Per", "initials": "P"}, {"family": "Sayin", "given": "Volkan I", "initials": "VI"}, {"family": "Bergo", "given": "Martin O", "initials": "MO"}], "type": "journal-article", "published": "2019-07-00", "journal": {"title": "Cell", "issn": "0092-8674", "volume": "178", "issue": "2", "pages": "330-345.e22", "issn-l": null}, "abstract": "For tumors to progress efficiently, cancer cells must overcome barriers of oxidative stress. Although dietary antioxidant supplementation or activation of endogenous antioxidants by NRF2 reduces oxidative stress and promotes early lung tumor progression, little is known about its effect on lung cancer metastasis. Here, we show that long-term supplementation with the antioxidants N-acetylcysteine and vitamin E promotes KRAS-driven lung cancer metastasis. The antioxidants stimulate metastasis by reducing levels of free heme and stabilizing the transcription factor BACH1. BACH1 activates transcription of Hexokinase 2 and Gapdh and increases glucose uptake, glycolysis rates, and lactate secretion, thereby stimulating glycolysis-dependent metastasis of mouse and human lung cancer cells. Targeting BACH1 normalized glycolysis and prevented antioxidant-induced metastasis, while increasing endogenous BACH1 expression stimulated glycolysis and promoted metastasis, also in the absence of antioxidants. We conclude that BACH1 stimulates glycolysis-dependent lung cancer metastasis and that BACH1 is activated under conditions of reduced oxidative stress.", "doi": "10.1016/j.cell.2019.06.005", "pmid": "31257027", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S0092-8674(19)30633-6"}], "notes": [], "created": "2020-01-23T16:14:45.454Z", "modified": "2021-06-21T09:53:06.509Z"}, {"entity": "publication", "iuid": "2f21fb5c0ac142b8b585f5f2d3380c06", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2f21fb5c0ac142b8b585f5f2d3380c06.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2f21fb5c0ac142b8b585f5f2d3380c06"}}, "title": "Peptide-Loaded Cubosomes Functioning as an Antimicrobial Unit against Escherichia coli.", "authors": [{"family": "Boge", "given": "Lukas", "initials": "L", "orcid": "0000-0003-4742-1702", "researcher": {"href": "https://publications.scilifelab.se/researcher/0cb0cbb9f32d49a2bec1b92d7cc69e8b.json"}}, {"family": "Browning", "given": "Kathryn L", "initials": "KL", "orcid": "0000-0002-0296-0369", "researcher": {"href": "https://publications.scilifelab.se/researcher/df7750ad8c9b4674827cb25d772619ca.json"}}, {"family": "Nordstr\u00f6m", "given": "Randi", "initials": "R", "orcid": "0000-0001-5626-3959", "researcher": {"href": "https://publications.scilifelab.se/researcher/2e70acd9b66345f8a28f68804e7ce376.json"}}, {"family": "Campana", "given": "Mario", "initials": "M"}, {"family": "Damgaard", "given": "Liv S E", "initials": "LSE"}, {"family": "Seth Caous", "given": "Josefin", "initials": "J"}, {"family": "Hellsing", "given": "Maja", "initials": "M", "orcid": "0000-0001-9613-0499", "researcher": {"href": "https://publications.scilifelab.se/researcher/0adc22e707c94fe696c51244b233d4ec.json"}}, {"family": "Ringstad", "given": "Lovisa", "initials": "L"}, {"family": "Andersson", "given": "Martin", "initials": "M"}], "type": "journal article", "published": "2019-06-19", "journal": {"title": "ACS Appl Mater Interfaces", "issn": "1944-8252", "volume": "11", "issue": "24", "pages": "21314-21322", "issn-l": "1944-8244"}, "abstract": "Dispersions of cubic liquid crystalline phases, also known as cubosomes, have shown great promise as delivery vehicles for a wide range of medicines. Due to their ordered structure, comprising alternating hydrophilic and hydrophobic domains, cubosomes possess unique delivery properties and compatibility with both water-soluble and -insoluble drugs. However, the drug delivery mechanism and cubosome interaction with human cells and bacteria are still poorly understood. Herein, we reveal how cubosomes loaded with the human cathelicidin antimicrobial peptide LL-37, a system with high bacteria-killing effect, interact with the bacterial membrane and provide new insights into the eradication mechanism. Combining the advanced experimental techniques neutron reflectivity and quartz crystal microbalance with dissipation monitoring, a mechanistic drug delivery model for LL-37-loaded cubosomes on bacterial mimicking bilayers was constructed. Moreover, the cubosome interaction with Escherichia coli was directly visualized using super-resolution laser scanning microscopy and cryogenic electron tomography. We could conclude that cubosomes loaded with LL-37 adsorbed and distorted bacterial membranes, providing evidence that the peptide-loaded cubosomes function as an antimicrobial unit.", "doi": "10.1021/acsami.9b01826", "pmid": "31120236", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2020-01-23T16:41:53.454Z", "modified": "2021-06-21T09:59:57.411Z"}, {"entity": "publication", "iuid": "200f9749c28742c2bd9c1629be8a4eb0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/200f9749c28742c2bd9c1629be8a4eb0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/200f9749c28742c2bd9c1629be8a4eb0"}}, "title": "Lipopolysaccharide-induced alteration of mitochondrial morphology induces a metabolic shift in microglia modulating the inflammatory response in vitro and in vivo.", "authors": [{"family": "Nair", "given": "Syam", "initials": "S", "orcid": "0000-0001-8470-2162", "researcher": {"href": "https://publications.scilifelab.se/researcher/733eacd288ce4eefaad48c391436a319.json"}}, {"family": "Sobotka", "given": "Kristina S", "initials": "KS"}, {"family": "Joshi", "given": "Pooja", "initials": "P"}, {"family": "Gressens", "given": "Pierre", "initials": "P"}, {"family": "Fleiss", "given": "Bobbi", "initials": "B"}, {"family": "Thornton", "given": "Claire", "initials": "C"}, {"family": "Mallard", "given": "Carina", "initials": "C"}, {"family": "Hagberg", "given": "Henrik", "initials": "H"}], "type": "journal article", "published": "2019-06-00", "journal": {"title": "Glia", "issn": "1098-1136", "volume": "67", "issue": "6", "pages": "1047-1061", "issn-l": "0894-1491"}, "abstract": "Accumulating evidence suggests that changes in the metabolic signature of microglia underlie their response to inflammation. We sought to increase our knowledge of how pro-inflammatory stimuli induce metabolic changes. Primary microglia exposed to lipopolysaccharide (LPS)-expressed excessive fission leading to more fragmented mitochondria than tubular mitochondria. LPS-mediated Toll-like receptor 4 (TLR4) activation also resulted in metabolic reprogramming from oxidative phosphorylation to glycolysis. Blockade of mitochondrial fission by Mdivi-1, a putative mitochondrial division inhibitor led to the reversal of the metabolic shift. Mdivi-1 treatment also normalized the changes caused by LPS exposure, namely an increase in mitochondrial reactive oxygen species production and mitochondrial membrane potential as well as accumulation of key metabolic intermediate of TCA cycle succinate. Moreover, Mdivi-1 treatment substantially reduced LPS induced cytokine and chemokine production. Finally, we showed that Mdivi-1 treatment attenuated expression of genes related to cytotoxic, repair, and immunomodulatory microglia phenotypes in an in vivo neuroinflammation paradigm. Collectively, our data show that the activation of microglia to a classically pro-inflammatory state is associated with a switch to glycolysis that is mediated by mitochondrial fission, a process which may be a pharmacological target for immunomodulation.", "doi": "10.1002/glia.23587", "pmid": "30637805", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2020-01-23T16:10:15.580Z", "modified": "2021-06-21T11:52:41.828Z"}, {"entity": "publication", "iuid": "937d831c14e34341b4f077cb46fda5fa", "links": {"self": {"href": "https://publications.scilifelab.se/publication/937d831c14e34341b4f077cb46fda5fa.json"}, "display": {"href": "https://publications.scilifelab.se/publication/937d831c14e34341b4f077cb46fda5fa"}}, "title": "A phototherapeutic fluorescent \u03b2-cyclodextrin branched polymer delivering nitric oxide.", "authors": [{"family": "Malanga", "given": "Milo", "initials": "M", "orcid": "0000-0001-7952-0268", "researcher": {"href": "https://publications.scilifelab.se/researcher/7fcc6d55602c46948f582f12df610170.json"}}, {"family": "Seggio", "given": "Mimimorena", "initials": "M"}, {"family": "Kirejev", "given": "Vladimir", "initials": "V"}, {"family": "Fraix", "given": "Aurore", "initials": "A"}, {"family": "Di Bari", "given": "Ivana", "initials": "I"}, {"family": "Fenyvesi", "given": "Eva", "initials": "E"}, {"family": "Ericson", "given": "Marica B", "initials": "MB", "orcid": "0000-0002-5987-5915", "researcher": {"href": "https://publications.scilifelab.se/researcher/af1f53e7cd234c36bdde7121e7204ed5.json"}}, {"family": "Sortino", "given": "Salvatore", "initials": "S", "orcid": "0000-0002-2086-1276", "researcher": {"href": "https://publications.scilifelab.se/researcher/78f156fd27a04054a2f8b4c5acca4c13.json"}}], "type": "journal article", "published": "2019-05-28", "journal": {"title": "Biomater Sci", "issn": "2047-4849", "volume": "7", "issue": "6", "pages": "2272-2276", "issn-l": "2047-4830"}, "abstract": "We report herein on a novel water-soluble \u03b2-cyclodextrin-branched polymer covalently integrating a fluorescein moiety and a nitric oxide (NO) photodonor within its macromolecular skeleton. Photoexcitation with visible light induces the parallel activation of the two chromophores, which results in the green fluorescence emission suitable for imaging accompanied by NO release for therapy. In fact, this polymer internalizes in squamous carcinoma cancer cells in vitro, visualized by fluorescence microscopy, and induces cell mortality as result of the NO photo-decaging. The non-covalent drug delivery capability of this new material is also demonstrated using a hydrophobic photosensitizer for photodynamic therapy as a probe.", "doi": "10.1039/c9bm00395a", "pmid": "31033967", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2020-01-23T16:08:38.456Z", "modified": "2021-06-21T13:47:58.258Z"}, {"entity": "publication", "iuid": "3742407b3e234cc5b35b0fbc1c4dda56", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3742407b3e234cc5b35b0fbc1c4dda56.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3742407b3e234cc5b35b0fbc1c4dda56"}}, "title": "Endocytosis, intracellular fate, accumulation, and agglomeration of titanium dioxide (TiO 2) nanoparticles in the rainbow trout liver cell line RTL-W1.", "authors": [{"family": "Lammel", "given": "Tobias", "initials": "T"}, {"family": "Mackevica", "given": "Aiga", "initials": "A"}, {"family": "Johansson", "given": "Bengt R", "initials": "BR"}, {"family": "Sturve", "given": "Joachim", "initials": "J"}], "type": "journal article", "published": "2019-05-00", "journal": {"title": "Environ Sci Pollut Res", "issn": "1614-7499", "volume": "26", "issue": "15", "pages": "15354-15372", "issn-l": "0944-1344"}, "abstract": "There is increasing evidence that titanium dioxide (TiO 2) nanoparticles (NPs) present in water or diet can be taken up by fish and accumulate in internal organs including the liver. However, their further fate in the organ is unknown. This study provides new insights into the interaction, uptake mechanism, intracellular trafficking, and fate of TiO2 NPs (Aeroxide\u00ae P25) in fish liver parenchymal cells (RTL-W1) in vitro using high-resolution transmission electron microscopy (TEM) and single particle inductively coupled plasma mass spectrometry (spICP-MS) as complementary analytical techniques. The results demonstrate that following their uptake via caveolae-mediated endocytosis, TiO2 NPs were trafficked through different intracellular compartments including early endosomes, multivesicular bodies, and late endosomes/endo-lysosomes, and eventually concentrated inside multilamellar vesicles. TEM and spICP-MS results provide evidence that uptake was nano-specific. Only NPs/NP agglomerates of a specific size range (~ 30-100 nm) were endocytosed; larger agglomerates were excluded from uptake and remained located in the extracellular space/exposure medium. NP number and mass inside cells increased linearly with time and was associated with an increase in particle diameter suggesting intracellular agglomeration/aggregation. No alterations in the expression of genes regulated by the redox balance-sensitive transcription factor Nrf-2 including superoxide dismutase, glutamyl cysteine ligase, glutathione synthetase, glutathione peroxidase, and glutathione S-transferase were observed. This shows that, despite the high intracellular NP burden (~ 3.9 \u00d7 102 ng Ti/mg protein after 24 h) and NP-interaction with mitochondria, cellular redox homeostasis was not significantly affected. This study contributes to a better mechanistic understanding of in vitro particokinetics as well as the potential fate and effects of TiO2 NPs in fish liver cells.", "doi": "10.1007/s11356-019-04856-1", "pmid": "30929178", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "10.1007/s11356-019-04856-1"}, {"db": "pmc", "key": "PMC6529399"}], "notes": [], "created": "2020-01-23T16:42:51.825Z", "modified": "2021-06-21T11:59:56.063Z"}, {"entity": "publication", "iuid": "0ec31b6de15d4b79a1806f6fa3da63ab", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0ec31b6de15d4b79a1806f6fa3da63ab.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0ec31b6de15d4b79a1806f6fa3da63ab"}}, "title": "AdipoR1 and AdipoR2 maintain membrane fluidity in most human cell types and independently of adiponectin.", "authors": [{"family": "Ruiz", "given": "Mario", "initials": "M"}, {"family": "St\u00e5hlman", "given": "Marcus", "initials": "M"}, {"family": "Bor\u00e9n", "given": "Jan", "initials": "J"}, {"family": "Pilon", "given": "Marc", "initials": "M", "orcid": "0000-0003-3919-2882", "researcher": {"href": "https://publications.scilifelab.se/researcher/d45c4ecf9afe463c971af2de53a770a8.json"}}], "type": "journal article", "published": "2019-05-00", "journal": {"title": "J. Lipid Res.", "issn": "1539-7262", "volume": "60", "issue": "5", "pages": "995-1004", "issn-l": "0022-2275"}, "abstract": "The FA composition of phospholipids must be tightly regulated to maintain optimal cell membrane properties and compensate for a highly variable supply of dietary FAs. Previous studies have shown that AdipoR2 and its homologue PAQR-2 are important regulators of phospholipid FA composition in HEK293 cells and Caenorhabditiselegans, respectively. Here we show that both AdipoR1 and AdipoR2 are essential for sustaining desaturase expression and high levels of unsaturated FAs in membrane phospholipids of many human cell types, including primary human umbilical vein endothelial cells, and for preventing membrane rigidification in cells challenged with exogenous palmitate, a saturated FA. Three independent methods confirm the role of the AdipoRs as regulators of membrane composition and fluidity: fluorescence recovery after photobleaching, measurements of Laurdan dye generalized polarization, and mass spectrometry to determine the FA composition of phospholipids. Furthermore, we show that the AdipoRs can prevent lipotoxicity in the complete absence of adiponectin, their putative ligand. We propose that the primary cellular function of AdipoR1 and AdipoR2 is to maintain membrane fluidity in most human cell types and that adiponectin is not required for this function.", "doi": "10.1194/jlr.M092494", "pmid": "30890562", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S0022-2275(20)32269-0"}, {"db": "pmc", "key": "PMC6495173"}], "notes": [], "created": "2020-01-23T16:12:25.516Z", "modified": "2021-06-21T12:00:27.451Z"}, {"entity": "publication", "iuid": "f7dda86f0d594272a6715566780299cb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f7dda86f0d594272a6715566780299cb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f7dda86f0d594272a6715566780299cb"}}, "title": "Pyroglutamation of amyloid-\u03b2x-42 (A\u03b2x-42) followed by A\u03b21-40 deposition underlies plaque polymorphism in progressing Alzheimer's disease pathology.", "authors": [{"family": "Michno", "given": "Wojciech", "initials": "W"}, {"family": "Nystr\u00f6m", "given": "Sofie", "initials": "S"}, {"family": "Wehrli", "given": "Patrick", "initials": "P"}, {"family": "Lashley", "given": "Tammaryn", "initials": "T"}, {"family": "Brinkmalm", "given": "Gunnar", "initials": "G"}, {"family": "Guerard", "given": "Laurent", "initials": "L"}, {"family": "Syv\u00e4nen", "given": "Stina", "initials": "S"}, {"family": "Sehlin", "given": "Dag", "initials": "D"}, {"family": "Kaya", "given": "Ibrahim", "initials": "I"}, {"family": "Brinet", "given": "Dimitri", "initials": "D"}, {"family": "Nilsson", "given": "K Peter R", "initials": "KPR"}, {"family": "Hammarstr\u00f6m", "given": "Per", "initials": "P"}, {"family": "Blennow", "given": "Kaj", "initials": "K"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H"}, {"family": "Hanrieder", "given": "J\u00f6rg", "initials": "J", "orcid": "0000-0001-6059-198X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e65454100674f98bf8f2575093f2441.json"}}], "type": "journal article", "published": "2019-04-26", "journal": {"title": "J. Biol. Chem.", "issn": "1083-351X", "volume": "294", "issue": "17", "pages": "6719-6732", "issn-l": "0021-9258"}, "abstract": "Amyloid-\u03b2 (A\u03b2) pathology in Alzheimer's disease (AD) is characterized by the formation of polymorphic deposits comprising diffuse and cored plaques. Because diffuse plaques are predominantly observed in cognitively unaffected, amyloid-positive (CU-AP) individuals, pathogenic conversion into cored plaques appears to be critical to AD pathogenesis. Herein, we identified the distinct A\u03b2 species associated with amyloid polymorphism in brain tissue from individuals with sporadic AD (s-AD) and CU-AP. To this end, we interrogated A\u03b2 polymorphism with amyloid conformation-sensitive dyes and a novel in situ MS paradigm for chemical characterization of hyperspectrally delineated plaque morphotypes. We found that maturation of diffuse into cored plaques correlated with increased A\u03b21-40 deposition. Using spatial in situ delineation with imaging MS (IMS), we show that A\u03b21-40 aggregates at the core structure of mature plaques, whereas A\u03b21-42 localizes to diffuse amyloid aggregates. Moreover, we observed that diffuse plaques have increased pyroglutamated A\u03b2x-42 levels in s-AD but not CU-AP, suggesting an AD pathology-related, hydrophobic functionalization of diffuse plaques facilitating A\u03b21-40 deposition. Experiments in tgAPPSwe mice verified that, similar to what has been observed in human brain pathology, diffuse deposits display higher levels of A\u03b21-42 and that A\u03b2 plaque maturation over time is associated with increases in A\u03b21-40. Finally, we found that A\u03b21-40 deposition is characteristic for cerebral amyloid angiopathy deposition and maturation in both humans and mice. These results indicate that N-terminal A\u03b2x-42 pyroglutamation and A\u03b21-40 deposition are critical events in priming and maturation of pathogenic A\u03b2 from diffuse into cored plaques, underlying neurotoxic plaque development in AD.", "doi": "10.1074/jbc.RA118.006604", "pmid": "30814252", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S0021-9258(20)36610-2"}, {"db": "pmc", "key": "PMC6497931"}], "notes": [], "created": "2020-01-23T16:09:06.452Z", "modified": "2021-06-21T12:01:24.675Z"}, {"entity": "publication", "iuid": "92a73e8398ef4faba901c3ef87c6ef1f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/92a73e8398ef4faba901c3ef87c6ef1f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/92a73e8398ef4faba901c3ef87c6ef1f"}}, "title": "Structural basis for adPEO-causing mutations in the mitochondrial TWINKLE helicase.", "authors": [{"family": "Peter", "given": "Bradley", "initials": "B"}, {"family": "Farge", "given": "Geraldine", "initials": "G"}, {"family": "Pardo-Hernandez", "given": "Carlos", "initials": "C"}, {"family": "T\u00e5ngefjord", "given": "Stefan", "initials": "S"}, {"family": "Falkenberg", "given": "Maria", "initials": "M"}], "type": "journal article", "published": "2019-04-01", "journal": {"title": "Hum. Mol. Genet.", "issn": "1460-2083", "volume": "28", "issue": "7", "pages": "1090-1099", "issn-l": "0964-6906"}, "abstract": "TWINKLE is the helicase involved in replication and maintenance of mitochondrial DNA (mtDNA) in mammalian cells. Structurally, TWINKLE is closely related to the bacteriophage T7 gp4 protein and comprises a helicase and primase domain joined by a flexible linker region. Mutations in and around this linker region are responsible for autosomal dominant progressive external ophthalmoplegia (adPEO), a neuromuscular disorder associated with deletions in mtDNA. The underlying molecular basis of adPEO-causing mutations remains unclear, but defects in TWINKLE oligomerization are thought to play a major role. In this study, we have characterized these disease variants by single-particle electron microscopy and can link the diminished activities of the TWINKLE variants to altered oligomeric properties. Our results suggest that the mutations can be divided into those that (i) destroy the flexibility of the linker region, (ii) inhibit ring closure and (iii) change the number of subunits within a helicase ring. Furthermore, we demonstrate that wild-type TWINKLE undergoes large-scale conformational changes upon nucleoside triphosphate binding and that this ability is lost in the disease-causing variants. This represents a substantial advancement in the understanding of the molecular basis of adPEO and related pathologies and may aid in the development of future therapeutic strategies.", "doi": "10.1093/hmg/ddy415", "pmid": "30496414", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "5217998"}, {"db": "pmc", "key": "PMC6423418"}], "notes": [], "created": "2020-01-23T16:29:45.013Z", "modified": "2021-06-21T12:06:17.034Z"}, {"entity": "publication", "iuid": "06e6b802d378407c9e89470e6fcfbf09", "links": {"self": {"href": "https://publications.scilifelab.se/publication/06e6b802d378407c9e89470e6fcfbf09.json"}, "display": {"href": "https://publications.scilifelab.se/publication/06e6b802d378407c9e89470e6fcfbf09"}}, "title": "Successful optimization of reconstruction parameters in structured illumination microscopy \u2013 A practical guide", "authors": [{"family": "Karras", "given": "Christian", "initials": "C"}, {"family": "Smedh", "given": "Maria", "initials": "M"}, {"family": "F\u00f6rster", "given": "Ronny", "initials": "R"}, {"family": "Deschout", "given": "Hendrik", "initials": "H"}, {"family": "Fernandez-Rodriguez", "given": "Julia", "initials": "J"}, {"family": "Heintzmann", "given": "Rainer", "initials": "R"}], "type": "journal-article", "published": "2019-04-00", "journal": {"title": "Optics Communications", "issn": "0030-4018", "volume": "436", "issue": null, "pages": "69-75", "issn-l": null}, "abstract": null, "doi": "10.1016/j.optcom.2018.12.005", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2020-01-23T16:42:24.839Z", "modified": "2023-06-19T13:47:48.766Z"}, {"entity": "publication", "iuid": "a014663cca0947d8baf49994504a6cd9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a014663cca0947d8baf49994504a6cd9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a014663cca0947d8baf49994504a6cd9"}}, "title": "Thickness determines microbial community structure and function in nitrifying biofilms via deterministic assembly.", "authors": [{"family": "Suarez", "given": "Carolina", "initials": "C", "orcid": "0000-0001-5988-4048", "researcher": {"href": "https://publications.scilifelab.se/researcher/86cadb16f7cf45eca8030af1a8ae860e.json"}}, {"family": "Piculell", "given": "Maria", "initials": "M"}, {"family": "Modin", "given": "Oskar", "initials": "O", "orcid": "0000-0002-9232-6096", "researcher": {"href": "https://publications.scilifelab.se/researcher/e1cfa2dd97cc472c9307498a65b5a8c6.json"}}, {"family": "Langenheder", "given": "Silke", "initials": "S"}, {"family": "Persson", "given": "Frank", "initials": "F"}, {"family": "Hermansson", "given": "Malte", "initials": "M"}], "type": "journal article", "published": "2019-03-25", "journal": {"volume": "9", "issn": "2045-2322", "issue": "1", "pages": "5110", "title": "Sci Rep", "issn-l": "2045-2322"}, "abstract": "Microbial biofilms are ubiquitous in aquatic environments where they provide important ecosystem functions. A key property believed to influence the community structure and function of biofilms is thickness. However, since biofilm thickness is inextricably linked to external factors such as water flow, temperature, development age and nutrient conditions, its importance is difficult to quantify. Here, we designed an experimental system in a wastewater treatment plant whereby nitrifying biofilms with different thicknesses (50 or 400 \u00b5m) were grown in a single reactor, and thus subjected to identical external conditions. The 50 and 400 \u00b5m biofilm communities were significantly different. This beta-diversity between biofilms of different thickness was primarily caused by deterministic factors. Turnover (species replacement) contributed more than nestedness (species loss) to the beta-diversity, i.e. the 50 \u00b5m communities were not simply a subset of the 400 \u00b5m communities. Moreover, the two communities differed in the composition of nitrogen-transforming bacteria and in nitrogen transformation rates. The study illustrates that biofilm thickness alone is a key driver for community composition and ecosystem function, which has implications for biotechnological applications and for our general understanding of biofilm ecology.", "doi": "10.1038/s41598-019-41542-1", "pmid": "30911066", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-019-41542-1"}, {"db": "pmc", "key": "PMC6434030"}], "notes": [], "created": "2020-01-23T16:13:32.374Z", "modified": "2021-06-16T14:44:51.298Z"}, {"entity": "publication", "iuid": "d9653ccf47d84737922af1de8442f144", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d9653ccf47d84737922af1de8442f144.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d9653ccf47d84737922af1de8442f144"}}, "title": "Differential Expression Patterns of Glycolytic Enzymes and Mitochondria-Dependent Apoptosis in PCOS Patients with Endometrial Hyperplasia, an Early Hallmark of Endometrial Cancer, In Vivo and the Impact of Metformin In Vitro.", "authors": [{"family": "Wang", "given": "Tao", "initials": "T"}, {"family": "Zhang", "given": "Jiao", "initials": "J"}, {"family": "Hu", "given": "Min", "initials": "M"}, {"family": "Zhang", "given": "Yuehui", "initials": "Y"}, {"family": "Cui", "given": "Peng", "initials": "P"}, {"family": "Li", "given": "Xin", "initials": "X"}, {"family": "Li", "given": "Juan", "initials": "J"}, {"family": "Vestin", "given": "Edvin", "initials": "E"}, {"family": "Br\u00e4nnstr\u00f6m", "given": "Mats", "initials": "M"}, {"family": "Shao", "given": "Linus R", "initials": "LR"}, {"family": "Billig", "given": "H\u00e5kan", "initials": "H"}], "type": "journal article", "published": "2019-01-24", "journal": {"title": "Int. J. Biol. Sci.", "issn": "1449-2288", "volume": "15", "issue": "3", "pages": "714-725", "issn-l": "1449-2288"}, "abstract": "The underlying mechanisms of polycystic ovarian syndrome (PCOS)-induced endometrial dysfunction are not fully understood, and although accumulating evidence shows that the use of metformin has beneficial effects in PCOS patients, the precise regulatory mechanisms of metformin on endometrial function under PCOS conditions have only been partially explored. To address these clinical challenges, this study aimed to assess the protein expression patterns of glycolytic enzymes, estrogen receptor (ER), and androgen receptor (AR) along with differences in mitochondria-dependent apoptosis in PCOS patients with and without endometrial hyperplasia in vivo and to investigate the effects of metformin in PCOS patients with endometrial hyperplasia in vitro. Here, we showed that compared to non-PCOS patients and PCOS patients without hyperplasia, the endometria from PCOS patients with hyperplasia had a distinct protein expression pattern of glycolytic enzymes, including pyruvate kinase isozyme M2 isoform (PKM2) and pyruvate dehydrogenase (PDH), and mitochondrial transcription factor A (TFAM). In PCOS patients with endometrial hyperplasia, increased glandular epithelial cell secretion and infiltrated stromal cells in the glands were associated with decreased PDH immunoreactivity in the epithelial cells. Using endometrial tissues from PCOS patients with hyperplasia, we found that in response to metformin treatment in vitro, hexokinase 2 (HK2) expression was decreased, whereas phosphofructokinase (PFK), PKM2, and lactate dehydrogenase A (LDHA) expression was increased compared to controls. Although there was no change in PDH expression, metformin treatment increased the expression of TFAM and cleaved caspase-3. Moreover, our in vivo study showed that while endometrial ER\u03b2 expression was no different between non-PCOS and PCOS patients regardless of whether or not hyperplasia was present, ER\u03b1 and AR protein expression was gradually increased in women with PCOS following the onset of endometrial hyperplasia. Our in vitro study showed that treatment with metformin inhibited ER\u03b1 expression without affecting ER\u03b2 expression. Our findings suggest that decreased glycolysis and increased mitochondrial activity might contribute to the onset of ER\u03b1-dependent endometrial hyperplasia and that metformin might directly reverse impaired glycolysis and normalize mitochondrial function in PCOS patients with endometrial hyperplasia.", "doi": "10.7150/ijbs.31425", "pmid": "30745857", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "ijbsv15p0714"}, {"db": "pmc", "key": "PMC6367580"}], "notes": [], "created": "2020-01-23T16:32:43.882Z", "modified": "2021-06-21T13:47:21.323Z"}, {"entity": "publication", "iuid": "a142c0c1ea884faa825c5a270ee4204e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a142c0c1ea884faa825c5a270ee4204e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a142c0c1ea884faa825c5a270ee4204e"}}, "title": "Trophic transfer of CuO NPs and dissolved Cu from sediment to worms to fish \u2013 a proof-of-concept study", "authors": [{"family": "Lammel", "given": "Tobias", "initials": "T", "orcid": "0000-0002-2224-460X", "researcher": {"href": "https://publications.scilifelab.se/researcher/0a7310be6c144cb38f159bb5fc866aed.json"}}, {"family": "Thit", "given": "Amalie", "initials": "A"}, {"family": "Mouneyrac", "given": "Catherine", "initials": "C"}, {"family": "Baun", "given": "Anders", "initials": "A"}, {"family": "Sturve", "given": "Joachim", "initials": "J"}, {"family": "Selck", "given": "Henriette", "initials": "H"}], "type": "journal-article", "published": "2019-00-00", "journal": {"title": "Environ. Sci.: Nano", "issn": "2051-8153", "issn-l": null, "volume": "6", "issue": "4", "pages": "1140-1155"}, "abstract": null, "doi": "10.1039/c9en00093c", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2020-01-23T16:47:10.502Z", "modified": "2021-06-22T11:10:42.200Z"}, {"entity": "publication", "iuid": "d0a86e672c904a24ab338bf0e45b366c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d0a86e672c904a24ab338bf0e45b366c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d0a86e672c904a24ab338bf0e45b366c"}}, "title": "Rainbow Trout Maintain Intestinal Transport and Barrier Functions Following Exposure to Polystyrene Microplastics.", "authors": [{"family": "A\u0161monait\u0117", "given": "Giedr\u0117", "initials": "G", "orcid": "0000-0002-4227-0792", "researcher": {"href": "https://publications.scilifelab.se/researcher/a302bcd21bb4413e82745682919cb25a.json"}}, {"family": "Sundh", "given": "Henrik", "initials": "H"}, {"family": "Asker", "given": "Noomi", "initials": "N"}, {"family": "Carney Almroth", "given": "Bethanie", "initials": "B", "orcid": "0000-0002-5037-4612", "researcher": {"href": "https://publications.scilifelab.se/researcher/5fca4df111d54f7da54cf4ac65d993e1.json"}}], "type": "journal article", "published": "2018-12-18", "journal": {"volume": "52", "issn": "1520-5851", "issue": "24", "pages": "14392-14401", "title": "Environ. Sci. Technol.", "issn-l": "0013-936X"}, "abstract": "Ingestion has been proposed as a prominent exposure route for plastic debris in aquatic organisms, including fish. While the consequences of ingestion of large plastic litter are mostly understood, the impacts resulting from ingestion of microplastics (MPs) are largely unknown. We designed a study that aimed to assess impacts of MPs on fish intestinal physiology and examined integrity of extrinsic, physical and immunological barriers. Rainbow trout were exposed to polystyrene (PS) MPs (100-400 \u03bcm) via feed for a period of 4 weeks. Fish were fed four types of diets: control, diets containing virgin PS particles, or particles exposed to two different environmental matrices (sewage or harbor effluent). Extrinsic barrier disturbance in intestinal tissue was evaluated via histology. The paracellular permeability toward ions and molecules was examined using Ussing chambers and mRNA expression analysis of tight junction proteins. Active transport was monitored as transepithelial potential difference, short-circuits current and uptake rate of amino acid 3H-lysine. Immune status parameters were measured through mRNA expression level of cytokines, lysozyme activity, and hematological analysis of immune cells. We could not show that PS MPs induced inflammatory responses or acted as physical or chemical hazards upon ingestion. No measurable effects were exerted on fish intestinal permeability, active transport or electrophysiology.", "doi": "10.1021/acs.est.8b04848", "pmid": "30451503", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2020-01-23T16:15:40.763Z", "modified": "2021-06-21T13:52:39.912Z"}, {"entity": "publication", "iuid": "7f8e9420dba5479c9212fb8fe5cc687e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7f8e9420dba5479c9212fb8fe5cc687e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7f8e9420dba5479c9212fb8fe5cc687e"}}, "title": "Membrane fluidity is regulated by the C. elegans transmembrane protein FLD-1 and its human homologs TLCD1/2.", "authors": [{"family": "Ruiz", "given": "Mario", "initials": "M"}, {"family": "Bodhicharla", "given": "Rakesh", "initials": "R"}, {"family": "Svensk", "given": "Emma", "initials": "E"}, {"family": "Devkota", "given": "Ranjan", "initials": "R"}, {"family": "Busayavalasa", "given": "Kiran", "initials": "K"}, {"family": "Palmgren", "given": "Henrik", "initials": "H"}, {"family": "St\u00e5hlman", "given": "Marcus", "initials": "M", "orcid": "0000-0002-4202-0339", "researcher": {"href": "https://publications.scilifelab.se/researcher/01a323cbf0a24269bd32bfc34539e021.json"}}, {"family": "Boren", "given": "Jan", "initials": "J"}, {"family": "Pilon", "given": "Marc", "initials": "M", "orcid": "0000-0003-3919-2882", "researcher": {"href": "https://publications.scilifelab.se/researcher/d45c4ecf9afe463c971af2de53a770a8.json"}}], "type": "journal article", "published": "2018-12-04", "journal": {"volume": "7", "issn": "2050-084X", "issue": null, "pages": null, "title": "Elife", "issn-l": "2050-084X"}, "abstract": "Dietary fatty acids are the main building blocks for cell membranes in animals, and mechanisms must therefore exist that compensate for dietary variations. We isolated C. elegans mutants that improved tolerance to dietary saturated fat in a sensitized genetic background, including eight alleles of the novel gene fld-1 that encodes a homolog of the human TLCD1 and TLCD2 transmembrane proteins. FLD-1 is localized on plasma membranes and acts by limiting the levels of highly membrane-fluidizing long-chain polyunsaturated fatty acid-containing phospholipids. Human TLCD1/2 also regulate membrane fluidity by limiting the levels of polyunsaturated fatty acid-containing membrane phospholipids. FLD-1 and TLCD1/2 do not regulate the synthesis of long-chain polyunsaturated fatty acids but rather limit their incorporation into phospholipids. We conclude that inhibition of FLD-1 or TLCD1/2 prevents lipotoxicity by allowing increased levels of membrane phospholipids that contain fluidizing long-chain polyunsaturated fatty acids.\n\nThis article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).", "doi": "10.7554/eLife.40686", "pmid": "30509349", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "40686"}, {"db": "pmc", "key": "PMC6279351"}], "notes": [], "created": "2020-01-23T16:16:17.610Z", "modified": "2021-06-21T13:54:44.388Z"}, {"entity": "publication", "iuid": "dfbb3b7a3b2745dfad321a142f1f58da", "links": {"self": {"href": "https://publications.scilifelab.se/publication/dfbb3b7a3b2745dfad321a142f1f58da.json"}, "display": {"href": "https://publications.scilifelab.se/publication/dfbb3b7a3b2745dfad321a142f1f58da"}}, "title": "Looking for a Treatment for Hailey-Hailey Disease: The Importance of Being Consistent in Case Reports.", "authors": [{"family": "Micaroni", "given": "Massimo", "initials": "M"}], "type": "journal article", "published": "2018-10-17", "journal": {"title": "J Cutan Med Surg", "issn": "1615-7109", "volume": "22", "issue": "6", "pages": "660", "issn-l": "1203-4754"}, "abstract": null, "doi": "10.1177/1203475418798021", "pmid": "30322310", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2020-01-23T16:26:36.113Z", "modified": "2021-06-21T14:02:00.956Z"}, {"entity": "publication", "iuid": "4c1a0c23d3734a1abdabf8418f403c99", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4c1a0c23d3734a1abdabf8418f403c99.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4c1a0c23d3734a1abdabf8418f403c99"}}, "title": "Exploring photoinactivation of microbial biofilms using laser scanning microscopy and confined 2-photon excitation.", "authors": [{"family": "Thomsen", "given": "Hanna", "initials": "H", "orcid": "0000-0001-6719-0919", "researcher": {"href": "https://publications.scilifelab.se/researcher/e54054e4c2d2407883628c54ee3ecd91.json"}}, {"family": "Graf", "given": "Fabrice E", "initials": "FE", "orcid": "0000-0003-1132-5348", "researcher": {"href": "https://publications.scilifelab.se/researcher/19da399357b94d0ba6119efcc2a44529.json"}}, {"family": "Farewell", "given": "Anne", "initials": "A", "orcid": "0000-0002-0841-4908", "researcher": {"href": "https://publications.scilifelab.se/researcher/a3e0018041984a31b07fe5e75bf9a03b.json"}}, {"family": "Ericson", "given": "Marica B", "initials": "MB", "orcid": "0000-0002-5987-5915", "researcher": {"href": "https://publications.scilifelab.se/researcher/af1f53e7cd234c36bdde7121e7204ed5.json"}}], "type": "journal article", "published": "2018-10-00", "journal": {"title": "J. Biophotonics", "issn": "1864-0648", "volume": "11", "issue": "10", "pages": "e201800018", "issn-l": "1864-063X"}, "abstract": "One pertinent complication in bacterial infection is the growth of biofilms, that is, communities of surface-adhered bacteria resilient to antibiotics. Photodynamic inactivation (PDI) has been proposed as an alternative to antibiotic treatment; however, novel techniques complementing standard efficacy measures are required. Herein, we present an approach employing multiphoton microscopy complemented with Airyscan super-resolution microscopy, to visualize the distribution of curcumin in Staphylococcus epidermidis biofilms. The effects of complexation of curcumin with hydroxypropyl-\u03b3-cyclodextrin (HP\u03b3CD) were studied. It was shown that HP\u03b3CD curcumin demonstrated higher bioavailability in the biofilms compared to curcumin, without affecting the subcellular uptake. Spectral quantification following PDI demonstrates a method for monitoring elimination of biofilms in real time using noninvasive 3D imaging. Additionally, spatially confined 2-photon inactivation was demonstrated for the first time in biofilms. These results support the feasibility of advanced optical microscopy as a sensitive tool for evaluating treatment efficacy in biofilms toward improved mechanistic studies of PDI.", "doi": "10.1002/jbio.201800018", "pmid": "29785840", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2020-01-23T16:31:34.212Z", "modified": "2021-06-21T14:03:45.729Z"}, {"entity": "publication", "iuid": "b7b9ef0a6fd2430895e7c3915a050c1a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b7b9ef0a6fd2430895e7c3915a050c1a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b7b9ef0a6fd2430895e7c3915a050c1a"}}, "title": "Attached stratified mucus separates bacteria from the epithelial cells in COPD lungs.", "authors": [{"family": "Fern\u00e1ndez-Blanco", "given": "Joan Antoni", "initials": "JA", "orcid": "0000-0002-1788-4928", "researcher": {"href": "https://publications.scilifelab.se/researcher/125daad02aad41c7a6bd1ff3e3e90606.json"}}, {"family": "Fakih", "given": "Dalia", "initials": "D"}, {"family": "Arike", "given": "Liisa", "initials": "L", "orcid": "0000-0002-2184-0960", "researcher": {"href": "https://publications.scilifelab.se/researcher/8a6ecb751dca49a598e3d13cc92ee5cf.json"}}, {"family": "Rodr\u00edguez-Pi\u00f1eiro", "given": "Ana M", "initials": "AM"}, {"family": "Mart\u00ednez-Abad", "given": "Beatriz", "initials": "B"}, {"family": "Skansebo", "given": "Elin", "initials": "E"}, {"family": "Jackson", "given": "Sonya", "initials": "S"}, {"family": "Root", "given": "James", "initials": "J"}, {"family": "Singh", "given": "Dave", "initials": "D"}, {"family": "McCrae", "given": "Christopher", "initials": "C"}, {"family": "Evans", "given": "Christopher M", "initials": "CM", "orcid": "0000-0001-5600-7314", "researcher": {"href": "https://publications.scilifelab.se/researcher/901e2d4d4d744476ac5f7467e5f42c73.json"}}, {"family": "\u00c5strand", "given": "Annika", "initials": "A"}, {"family": "Ermund", "given": "Anna", "initials": "A"}, {"family": "Hansson", "given": "Gunnar C", "initials": "GC", "orcid": "0000-0002-1900-1869", "researcher": {"href": "https://publications.scilifelab.se/researcher/44b3815603154322a6dac16f2fc1c1e9.json"}}], "type": "journal article", "published": "2018-09-06", "journal": {"title": "JCI Insight", "issn": "2379-3708", "volume": "3", "issue": "17", "pages": null, "issn-l": "2379-3708"}, "abstract": "The respiratory tract is normally kept essentially free of bacteria by cilia-mediated mucus transport, but in chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF), bacteria and mucus accumulates instead. To address the mechanisms behind the mucus accumulation, the proteome of bronchoalveolar lavages from COPD patients and mucus collected in an elastase-induced mouse model of COPD was analyzed, revealing similarities with each other and with the protein content in colonic mucus. Moreover, stratified laminated sheets of mucus were observed in airways from patients with CF and COPD and in elastase-exposed mice. On the other hand, the mucus accumulation in the elastase model was reduced in Muc5b-KO mice. While mucus plugs were removed from airways by washing with hypertonic saline in the elastase model, mucus remained adherent to epithelial cells. Bacteria were trapped on this mucus, whereas, in non-elastase-treated mice, bacteria were found on the epithelial cells. We propose that the adherence of mucus to epithelial cells observed in CF, COPD, and the elastase-induced mouse model of COPD separates bacteria from the surface cells and, thus, protects the respiratory epithelium.", "doi": "10.1172/jci.insight.120994", "pmid": "30185674", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "120994"}, {"db": "pmc", "key": "PMC6171804"}], "notes": [], "created": "2020-01-23T16:21:04.403Z", "modified": "2021-06-21T14:06:50.099Z"}, {"entity": "publication", "iuid": "ff9fdc97ac634719bc931f7156f70028", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ff9fdc97ac634719bc931f7156f70028.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ff9fdc97ac634719bc931f7156f70028"}}, "title": "Interactions between monomeric CCT\u03b4 and p150 Glued: A novel function for CCT\u03b4 at the cell periphery distinct from the protein folding activity of the molecular chaperone CCT.", "authors": [{"family": "Echbarthi", "given": "Meriem", "initials": "M"}, {"family": "Vallin", "given": "Josefine", "initials": "J"}, {"family": "Grantham", "given": "Julie", "initials": "J"}], "type": "journal article", "published": "2018-09-01", "journal": {"title": "Exp. Cell Res.", "issn": "1090-2422", "volume": "370", "issue": "1", "pages": "137-149", "issn-l": "0014-4827"}, "abstract": "Chaperonin containing tailless complex polypeptide 1 (CCT) is a molecular chaperone consisting of eight distinct protein subunits, that when oligomeric is essential for the folding of newly synthesized tubulin and actin. In addition to folding, CCT activity includes functions of individual subunits in their monomeric form. For example, when CCT\u03b4 monomer levels are increased in cultured mammalian cells, numerous cell surface protrusions are formed from retraction fibres, indicating that an underlying function for the CCT\u03b4 monomer exists. Here, using a yeast two-hybrid screen we identify the dynactin complex component p150 Glued as a binding partner for CCT\u03b4 and show by siRNA depletion that this interaction is required for the formation of CCT\u03b4-induced cell surface protrusions. Intact microtubules are necessary for the formation of the protrusions, consistent with microtubule minus end transport driving the retraction fibre formation and depletion of either p150Glued or the dynactin complex-associated transmembrane protein dynAP prevents the previously observed localization of GFP-CCT\u03b4 to the plasma membrane. Wound healing assays reveal that CCT\u03b4 monomer levels influence directional cell migration and together our observations demonstrate that in addition to the folding activity of CCT in its oligomer form, a monomeric subunit is associated with events that involve the assembled cytoskeleton.", "doi": "10.1016/j.yexcr.2018.06.018", "pmid": "29913154", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S0014-4827(18)30347-1"}], "notes": [], "created": "2020-01-23T16:20:33.741Z", "modified": "2021-06-21T14:07:00.474Z"}, {"entity": "publication", "iuid": "e9757d6c5f3c4e2fb6047d56b6575099", "links": {"self": {"href": "https://publications.scilifelab.se/publication/e9757d6c5f3c4e2fb6047d56b6575099.json"}, "display": {"href": "https://publications.scilifelab.se/publication/e9757d6c5f3c4e2fb6047d56b6575099"}}, "title": "STK25 regulates oxidative capacity and metabolic efficiency in adipose tissue.", "authors": [{"family": "S\u00fctt", "given": "Silva", "initials": "S"}, {"family": "Cansby", "given": "Emmelie", "initials": "E"}, {"family": "Paul", "given": "Alexandra", "initials": "A"}, {"family": "Amrutkar", "given": "Manoj", "initials": "M"}, {"family": "Nu\u00f1ez-Dur\u00e1n", "given": "Esther", "initials": "E"}, {"family": "Kulkarni", "given": "Nagaraj M", "initials": "NM"}, {"family": "St\u00e5hlman", "given": "Marcus", "initials": "M"}, {"family": "Bor\u00e9n", "given": "Jan", "initials": "J"}, {"family": "Laurencikiene", "given": "Jurga", "initials": "J"}, {"family": "Howell", "given": "Brian W", "initials": "BW"}, {"family": "Enerb\u00e4ck", "given": "Sven", "initials": "S"}, {"family": "Mahlapuu", "given": "Margit", "initials": "M"}], "type": "journal article", "published": "2018-09-00", "journal": {"volume": "238", "issn": "1479-6805", "issue": "3", "pages": "187-202", "title": "J Endocrinol", "issn-l": null}, "abstract": "Whole-body energy homeostasis at over-nutrition critically depends on how well adipose tissue remodels in response to excess calories. We recently identified serine/threonine protein kinase (STK)25 as a critical regulator of ectopic lipid storage in non-adipose tissue and systemic insulin resistance in the context of nutritional stress. Here, we investigated the role of STK25 in regulation of adipose tissue dysfunction in mice challenged with a high-fat diet. We found that overexpression of STK25 in high-fat-fed mice resulted in impaired mitochondrial function and aggravated hypertrophy, inflammatory infiltration and fibrosis in adipose depots. Reciprocally, Stk25-knockout mice displayed improved mitochondrial function and were protected against diet-induced excessive fat storage, meta-inflammation and fibrosis in brown and white adipose tissues. Furthermore, in rodent HIB-1B cell line, STK25 depletion resulted in enhanced mitochondrial activity and consequently, reduced lipid droplet size, demonstrating an autonomous action for STK25 within adipocytes. In summary, we provide the first evidence for a key function of STK25 in controlling the metabolic balance of lipid utilization vs lipid storage in brown and white adipose depots, suggesting that repression of STK25 activity offers a potential strategy for establishing healthier adipose tissue in the context of chronic exposure to dietary lipids.", "doi": "10.1530/JOE-18-0182", "pmid": "29794231", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "JOE-18-0182"}], "notes": [], "created": "2020-01-23T16:31:20.036Z", "modified": "2021-06-21T14:07:15.086Z"}, {"entity": "publication", "iuid": "7385440a648e4721bdf0bdfa5fa73032", "links": {"self": {"href": "https://publications.scilifelab.se/publication/7385440a648e4721bdf0bdfa5fa73032.json"}, "display": {"href": "https://publications.scilifelab.se/publication/7385440a648e4721bdf0bdfa5fa73032"}}, "title": "Membrane Fluidity Is Regulated Cell Nonautonomously by Caenorhabditiselegans PAQR-2 and Its Mammalian Homolog AdipoR2.", "authors": [{"family": "Bodhicharla", "given": "Rakesh", "initials": "R"}, {"family": "Devkota", "given": "Ranjan", "initials": "R"}, {"family": "Ruiz", "given": "Mario", "initials": "M"}, {"family": "Pilon", "given": "Marc", "initials": "M", "orcid": "0000-0003-3919-2882", "researcher": {"href": "https://publications.scilifelab.se/researcher/d45c4ecf9afe463c971af2de53a770a8.json"}}], "type": "journal article", "published": "2018-09-00", "journal": {"title": "Genetics", "issn": "1943-2631", "volume": "210", "issue": "1", "pages": "189-201", "issn-l": "0016-6731"}, "abstract": "Maintenance of membrane properties is an essential aspect of cellular homeostasis of which the regulatory mechanisms remain mostly uncharacterized. In Caenorhabditis elegans, the PAQR-2 and IGLR-2 proteins act together as a plasma membrane sensor that responds to decreased fluidity by promoting fatty acid desaturation, hence restoring membrane fluidity. Here, we used mosaic analysis for paqr-2 and iglr-2, and tissue-specific paqr-2 expression, to show that membrane homeostasis is achieved cell nonautonomously. Specifically, we found that expression of paqr-2 in the hypodermis, gonad sheath cells, or intestine is sufficient to suppress systemic paqr-2 mutant phenotypes, including tail tip morphology, membrane fluidity in intestinal cells, cold and glucose intolerance, vitellogenin transport to the germline, germ cell development, and brood size. Finally, we show that the cell nonautonomous regulation of membrane homeostasis is conserved in human cells: HEK293 cells that express AdipoR2, a homolog of paqr-2, are able to normalize membrane fluidity in distant cells where AdipoR2 has been silenced. Finally, using C. elegans mutants and small interfering RNA against \u03949 stearoyl-CoA desaturase in HEK293 cells, we show that \u03949 desaturases are essential for the cell nonautonomous maintenance of membrane fluidity. We conclude that cells are able to share membrane components even when they are not in direct contact with each other, and that this contributes to the maintenance of membrane homeostasis in C. elegans and human cells.", "doi": "10.1534/genetics.118.301272", "pmid": "29997234", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "genetics.118.301272"}, {"db": "pmc", "key": "PMC6116961"}], "notes": [], "created": "2020-01-23T16:16:39.298Z", "modified": "2021-06-21T14:08:01.320Z"}, {"entity": "publication", "iuid": "8e1017eec18e41fca1dc458d502125d5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8e1017eec18e41fca1dc458d502125d5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8e1017eec18e41fca1dc458d502125d5"}}, "title": "Detailed analysis of the plasma extracellular vesicle proteome after separation from lipoproteins", "authors": [{"family": "Karimi", "given": "Nasibeh", "initials": "N"}, {"family": "Cvjetkovic", "given": "Aleksander", "initials": "A"}, {"family": "Jang", "given": "Su Chul", "initials": "SC"}, {"family": "Crescitelli", "given": "Rossella", "initials": "R"}, {"family": "Hosseinpour Feizi", "given": "Mohammad Ali", "initials": "MA"}, {"family": "Nieuwland", "given": "Rienk", "initials": "R"}, {"family": "L\u00f6tvall", "given": "Jan", "initials": "J"}, {"family": "L\u00e4sser", "given": "Cecilia", "initials": "C"}], "type": "journal-article", "published": "2018-08-00", "journal": {"volume": "75", "issn": "1420-682X", "issue": "15", "pages": "2873-2886", "title": "Cell. Mol. Life Sci.", "issn-l": null}, "abstract": "The isolation of extracellular vesicles (EVs) from blood is of great importance to understand the biological role of circulating EVs and to develop EVs as biomarkers of disease. Due to the concurrent presence of lipoprotein particles, however, blood is one of the most difficult body fluids to isolate EVs from. The aim of this study was to develop a robust method to isolate and characterise EVs from blood with minimal contamination by plasma proteins and lipoprotein particles. Plasma and serum were collected from healthy subjects, and EVs were isolated by size-exclusion chromatography (SEC), with most particles being present in fractions 8-12, while the bulk of the plasma proteins was present in fractions 11-28. Vesicle markers peaked in fractions 7-11; however, the same fractions also contained lipoprotein particles. The purity of EVs was improved by combining a density cushion with SEC to further separate lipoprotein particles from the vesicles, which reduced the contamination of lipoprotein particles by 100-fold. Using this novel isolation procedure, a total of 1187 proteins were identified in plasma EVs by mass spectrometry, of which several proteins are known as EV-associated proteins but have hitherto not been identified in the previous proteomic studies of plasma EVs. This study shows that SEC alone is unable to completely separate plasma EVs from lipoprotein particles. However, combining SEC with a density cushion significantly improved the separation of EVs from lipoproteins and allowed for a detailed analysis of the proteome of plasma EVs, thus making blood a viable source for EV biomarker discovery.", "doi": "10.1007/s00018-018-2773-4", "pmid": "29441425", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service", "Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [], "notes": [], "created": "2020-01-23T16:22:57.548Z", "modified": "2024-01-16T13:46:32.280Z"}, {"entity": "publication", "iuid": "dda4d85de2cd439395be3e3bcc05281d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/dda4d85de2cd439395be3e3bcc05281d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/dda4d85de2cd439395be3e3bcc05281d"}}, "title": "Glyco-engineered cell line and computational docking studies reveals enterotoxigenic Escherichia coli CFA/I fimbriae bind to Lewis a glycans.", "authors": [{"family": "Mottram", "given": "Lynda", "initials": "L"}, {"family": "Liu", "given": "Jining", "initials": "J"}, {"family": "Chavan", "given": "Sonali", "initials": "S"}, {"family": "Tobias", "given": "Joshua", "initials": "J"}, {"family": "Svennerholm", "given": "Ann-Mari", "initials": "AM"}, {"family": "Holgersson", "given": "Jan", "initials": "J"}], "type": "journal article", "published": "2018-07-26", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "8", "issue": "1", "pages": "11250", "issn-l": "2045-2322"}, "abstract": "We have previously reported clinical data to suggest that colonization factor I (CFA/I) fimbriae of enterotoxigenic Escherichia coli (ETEC) can bind to Lewis a (Le a), a glycan epitope ubiquitous in the small intestinal mucosa of young children (<2 years of age), and individuals with a genetic mutation of FUT2. To further elucidate the physiological binding properties of this interaction, we engineered Chinese Hamster Ovary (CHO-K1) cells to express Lea or Leb determinants on both N- and O-glycans. We used our glyco-engineered CHO-K1 cell lines to demonstrate that CfaB, the major subunit of ETEC CFA/I fimbriae, as well as four related ETEC fimbriae, bind more to our CHO-K1 cell-line expressing Lea, compared to cells carrying Leb or the CHO-K1 wild-type glycan phenotype. Furthermore, using in-silico docking analysis, we predict up to three amino acids (Glu25, Asn27, Thr29) found in the immunoglobulin (Ig)-like groove region of CfaB of CFA/I and related fimbriae, could be important for the preferential and higher affinity binding of CFA/I fimbriae to the potentially structurally flexible Lea glycan. These findings may lead to a better molecular understanding of ETEC pathogenesis, aiding in the development of vaccines and/or anti-infection therapeutics.", "doi": "10.1038/s41598-018-29258-0", "pmid": "30050155", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-018-29258-0"}, {"db": "pmc", "key": "PMC6062558"}], "notes": [], "created": "2020-01-23T16:27:24.079Z", "modified": "2021-06-21T13:55:45.320Z"}, {"entity": "publication", "iuid": "f0b96ae0319a4ebb931475fad35ad00b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f0b96ae0319a4ebb931475fad35ad00b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f0b96ae0319a4ebb931475fad35ad00b"}}, "title": "Multimodal Chemical Imaging of Amyloid Plaque Polymorphism Reveals A\u03b2 Aggregation Dependent Anionic Lipid Accumulations and Metabolism.", "authors": [{"family": "Michno", "given": "Wojciech", "initials": "W"}, {"family": "Kaya", "given": "Ibrahim", "initials": "I"}, {"family": "Nystr\u00f6m", "given": "Sofie", "initials": "S"}, {"family": "Guerard", "given": "Laurent", "initials": "L"}, {"family": "Nilsson", "given": "K Peter R", "initials": "KPR", "orcid": "0000-0002-5582-140X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9c151458a1cb4a3d838c2c25d880d188.json"}}, {"family": "Hammarstr\u00f6m", "given": "Per", "initials": "P", "orcid": "0000-0001-5827-3587", "researcher": {"href": "https://publications.scilifelab.se/researcher/a7b588c389624c9ca28b0bd141cbca58.json"}}, {"family": "Blennow", "given": "Kaj", "initials": "K"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H"}, {"family": "Hanrieder", "given": "J\u00f6rg", "initials": "J", "orcid": "0000-0001-6059-198X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e65454100674f98bf8f2575093f2441.json"}}], "type": "journal article", "published": "2018-07-03", "journal": {"volume": "90", "issn": "1520-6882", "issue": "13", "pages": "8130-8138", "title": "Anal. Chem.", "issn-l": "0003-2700"}, "abstract": "Amyloid plaque formation constitutes one of the main pathological hallmarks of Alzheimer's disease (AD) and is suggested to be a critical factor driving disease pathogenesis. Interestingly, in patients that display amyloid pathology but remain cognitively normal, A\u03b2 deposits are predominantly of diffuse morphology suggesting that cored plaque formation is primarily associated with cognitive deterioration and AD pathogenesis. Little is known about the molecular mechanism responsible for conversion of monomeric A\u03b2 into neurotoxic aggregates and the predominantly cored deposits observed in AD. The structural diversity among A\u03b2 plaques, including cored/compact- and diffuse, may be linked to their distinct A\u03b2 profile and other chemical species including neuronal lipids. We developed a novel, chemical imaging paradigm combining matrix assisted laser desorption/ionization imaging mass spectrometry (MALDI IMS) and fluorescent amyloid staining. This multimodal imaging approach was used to probe the lipid chemistry associated with structural plaque heterogeneity in transgenic AD mice (tgAPP Swe) and was correlated to A\u03b2 profiles determined by subsequent laser microdissection and immunoprecipitation-mass spectrometry. Multivariate image analysis revealed an inverse localization of ceramides and their matching metabolites to diffuse and cored structures within single plaques, respectively. Moreover, phosphatidylinositols implicated in AD pathogenesis, were found to localize to the diffuse A\u03b2 structures and correlate with A\u03b21-42. Further, lysophospholipids implicated in neuroinflammation were increased in all A\u03b2 deposits. The results support previous clinical findings on the importance of lipid disturbances in AD pathophysiology and associated sphingolipid processing. These data highlight the potential of multimodal imaging as a powerful technology to probe neuropathological mechanisms.", "doi": "10.1021/acs.analchem.8b01361", "pmid": "29856605", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2020-01-23T16:27:05.285Z", "modified": "2021-06-21T14:23:29.254Z"}, {"entity": "publication", "iuid": "4be560e925f7466da8744a3a30a77a26", "links": {"self": {"href": "https://publications.scilifelab.se/publication/4be560e925f7466da8744a3a30a77a26.json"}, "display": {"href": "https://publications.scilifelab.se/publication/4be560e925f7466da8744a3a30a77a26"}}, "title": "Increased Neuronal Differentiation of Neural Progenitor Cells Derived from Phosphovimentin-Deficient Mice.", "authors": [{"family": "Chen", "given": "Meng", "initials": "M"}, {"family": "Puschmann", "given": "Till B", "initials": "TB"}, {"family": "Marasek", "given": "Pavel", "initials": "P"}, {"family": "Inagaki", "given": "Masaki", "initials": "M"}, {"family": "Pekna", "given": "Marcela", "initials": "M"}, {"family": "Wilhelmsson", "given": "Ulrika", "initials": "U"}, {"family": "Pekny", "given": "Milos", "initials": "M"}], "type": "journal article", "published": "2018-07-00", "journal": {"title": "Mol Neurobiol", "issn": "1559-1182", "volume": "55", "issue": "7", "pages": "5478-5489", "issn-l": "0893-7648"}, "abstract": "Vimentin is an intermediate filament (also known as nanofilament) protein expressed in several cell types of the central nervous system, including astrocytes and neural stem/progenitor cells. Mutation of the vimentin serine sites that are phosphorylated during mitosis (VIM SA/SA ) leads to cytokinetic failures in fibroblasts and lens epithelial cells, resulting in chromosomal instability and increased expression of cell senescence markers. In this study, we investigated morphology, proliferative capacity, and motility of VIM SA/SA astrocytes, and their effect on the differentiation of neural stem/progenitor cells. VIM SA/SA astrocytes expressed less vimentin and more GFAP but showed a well-developed intermediate filament network, exhibited normal cell morphology, proliferation, and motility in an in vitro wound closing assay. Interestingly, we found a two- to fourfold increased neuronal differentiation of VIM SA/SA neurosphere cells, both in a standard 2D and in Bioactive3D cell culture systems, and determined that this effect was neurosphere cell autonomous and not dependent on cocultured astrocytes. Using BrdU in vivo labeling to assess neural stem/progenitor cell proliferation and differentiation in the hippocampus of adult mice, one of the two major adult neurogenic regions, we found a modest increase (by 8%) in the fraction of newly born and surviving neurons. Thus, mutation of the serine sites phosphorylated in vimentin during mitosis alters intermediate filament protein expression but has no effect on astrocyte morphology or proliferation, and leads to increased neuronal differentiation of neural progenitor cells.", "doi": "10.1007/s12035-017-0759-0", "pmid": "28956310", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "10.1007/s12035-017-0759-0"}, {"db": "pmc", "key": "PMC5994207"}], "notes": [], "created": "2020-01-23T16:18:22.734Z", "modified": "2021-06-21T14:25:05.792Z"}, {"entity": "publication", "iuid": "a3139a26895a430891c8fa3b9b10f540", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a3139a26895a430891c8fa3b9b10f540.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a3139a26895a430891c8fa3b9b10f540"}}, "title": "Calcium-activated Chloride Channel Regulator 1 (CLCA1) Controls Mucus Expansion in Colon by Proteolytic Activity.", "authors": [{"family": "Nystr\u00f6m", "given": "Elisabeth E L", "initials": "EEL"}, {"family": "Birchenough", "given": "George M H", "initials": "GMH"}, {"family": "van der Post", "given": "Sjoerd", "initials": "S"}, {"family": "Arike", "given": "Liisa", "initials": "L"}, {"family": "Gruber", "given": "Achim D", "initials": "AD"}, {"family": "Hansson", "given": "Gunnar C", "initials": "GC"}, {"family": "Johansson", "given": "Malin E V", "initials": "MEV", "orcid": "0000-0002-4237-6677", "researcher": {"href": "https://publications.scilifelab.se/researcher/520dab35c19049c8b3f1083a92e60d56.json"}}], "type": "journal article", "published": "2018-07-00", "journal": {"title": "EBioMedicine", "issn": "2352-3964", "volume": "33", "issue": null, "pages": "134-143", "issn-l": "2352-3964"}, "abstract": "Many epithelial surfaces of the body are covered with protective mucus, and disrupted mucus homeostasis is coupled to diseases such as ulcerative colitis, helminth infection, cystic fibrosis, and chronic obstructive lung disease. However, little is known how a balanced mucus system is maintained. By investigating the involvement of proteases in colonic mucus dynamics we identified metalloprotease activity to be a key contributor to mucus expansion. The effect was mediated by calcium-activated chloride channel regulator 1 (CLCA1) as application of recombinant CLCA1 on intestinal mucus in freshly dissected tissue resulted in increased mucus thickness independently of ion and mucus secretion, but dependent on its metallohydrolase activity. Further, CLCA1 modulated mucus dynamics in both human and mouse, and knock-out of CLCA1 in mice was compensated for by cysteine proteases. Our results suggest that CLCA1 is involved in intestinal mucus homeostasis by facilitating processing and removal of mucus to prevent stagnation. In light of our findings, we suggest future studies to investigate if upregulation of CLCA1 in diseases associated with mucus accumulation could facilitate removal of mucus in an attempt to maintain homeostasis.", "doi": "10.1016/j.ebiom.2018.05.031", "pmid": "29885864", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S2352-3964(18)30196-8"}, {"db": "pmc", "key": "PMC6085540"}], "notes": [], "created": "2020-01-23T16:29:14.575Z", "modified": "2021-06-21T14:24:55.291Z"}, {"entity": "publication", "iuid": "d694db60ffa047b59df9c8f0dd2b8085", "links": {"self": {"href": "https://publications.scilifelab.se/publication/d694db60ffa047b59df9c8f0dd2b8085.json"}, "display": {"href": "https://publications.scilifelab.se/publication/d694db60ffa047b59df9c8f0dd2b8085"}}, "title": "Assessment of titanium dioxide nanoparticle toxicity in the rainbow trout (Onchorynchus mykiss) liver and gill cell lines RTL-W1 and RTgill-W1 under particular consideration of nanoparticle stability and interference with fluorometric assays", "authors": [{"family": "Lammel", "given": "Tobias", "initials": "T"}, {"family": "Sturve", "given": "Joachim", "initials": "J"}], "type": "journal-article", "published": "2018-07-00", "journal": {"title": "NanoImpact", "issn": "2452-0748", "volume": "11", "issue": null, "pages": "1-19", "issn-l": "2452-0748"}, "abstract": null, "doi": "10.1016/j.impact.2018.01.001", "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2020-01-23T16:51:08.214Z", "modified": "2023-06-19T13:50:05.323Z"}, {"entity": "publication", "iuid": "2e77c536a8b44468a4ac3e357ddf6b32", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2e77c536a8b44468a4ac3e357ddf6b32.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2e77c536a8b44468a4ac3e357ddf6b32"}}, "title": "Confined photo-release of nitric oxide with simultaneous two-photon fluorescence tracking in a cellular system.", "authors": [{"family": "Thomsen", "given": "Hanna", "initials": "H", "orcid": "0000-0001-6719-0919", "researcher": {"href": "https://publications.scilifelab.se/researcher/e54054e4c2d2407883628c54ee3ecd91.json"}}, {"family": "Marino", "given": "Nino", "initials": "N"}, {"family": "Conoci", "given": "Sabrina", "initials": "S"}, {"family": "Sortino", "given": "Salvatore", "initials": "S", "orcid": "0000-0002-2086-1276", "researcher": {"href": "https://publications.scilifelab.se/researcher/78f156fd27a04054a2f8b4c5acca4c13.json"}}, {"family": "Ericson", "given": "Marica B", "initials": "MB", "orcid": "0000-0002-5987-5915", "researcher": {"href": "https://publications.scilifelab.se/researcher/af1f53e7cd234c36bdde7121e7204ed5.json"}}], "type": "journal article", "published": "2018-06-27", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "8", "issue": "1", "pages": "9753", "issn-l": "2045-2322"}, "abstract": "Nitric oxide (NO) is a key signaling molecule in biological systems. New tools are required to therapeutically modulate NO levels with confined precision. This study explores the photoactivatable properties of an NO releasing compound (CPA), based on cupferron O-alkylated with an anthracene derivative. Upon light stimulation, CPA uncages two species: cupferron, which liberates NO, and an anthrylmethyl carbocation, which evolves into a fluorescent reporter. Proof-of-principle is demonstrated using one- and two-photon excitation (1PE and 2PE) in a cellular system (A431 cells). It was found that 1PE induces cell toxicity, while 2PE does not. Since 1PE using UV light is more likely to generate cellular photodamage, the cell toxicity observed using 1PE is most likely a combinatory effect of NO release and other UV-induced damage, which should be subject to further investigation. On the other hand, absence of phototoxicity using 2PE suggests that NO alone is not cytotoxic. This leads to the conclusion that the concept of 2PE photorelease of NO from CPA enable opportunities for biological studies of NO signaling with confined precision of NO release with minimal cytotoxicity.", "doi": "10.1038/s41598-018-27939-4", "pmid": "29950654", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-018-27939-4"}, {"db": "pmc", "key": "PMC6021447"}], "notes": [], "created": "2020-01-23T16:31:54.073Z", "modified": "2021-06-21T13:59:16.663Z"}, {"entity": "publication", "iuid": "b0ed6f062b654d878f8303393de58d01", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b0ed6f062b654d878f8303393de58d01.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b0ed6f062b654d878f8303393de58d01"}}, "title": "Gut microbiota regulates maturation of the adult enteric nervous system via enteric serotonin networks.", "authors": [{"family": "De Vadder", "given": "Filipe", "initials": "F"}, {"family": "Grasset", "given": "Estelle", "initials": "E"}, {"family": "Manner\u00e5s Holm", "given": "Louise", "initials": "L"}, {"family": "Karsenty", "given": "G\u00e9rard", "initials": "G"}, {"family": "Macpherson", "given": "Andrew J", "initials": "AJ"}, {"family": "Olofsson", "given": "Louise E", "initials": "LE"}, {"family": "B\u00e4ckhed", "given": "Fredrik", "initials": "F", "orcid": "0000-0002-4871-8818", "researcher": {"href": "https://publications.scilifelab.se/researcher/1689878e0c5542d08d3e2d5043a6ce5c.json"}}], "type": "journal article", "published": "2018-06-19", "journal": {"volume": "115", "issn": "1091-6490", "issue": "25", "pages": "6458-6463", "title": "Proc. Natl. Acad. Sci. U.S.A.", "issn-l": "0027-8424"}, "abstract": "The enteric nervous system (ENS) is crucial for essential gastrointestinal physiologic functions such as motility, fluid secretion, and blood flow. The gut is colonized by trillions of bacteria that regulate host production of several signaling molecules including serotonin (5-HT) and other hormones and neurotransmitters. Approximately 90% of 5-HT originates from the intestine, and activation of the 5-HT 4 receptor in the ENS has been linked to adult neurogenesis and neuroprotection. Here, we tested the hypothesis that the gut microbiota could induce maturation of the adult ENS through release of 5-HT and activation of 5-HT4 receptors. Colonization of germ-free mice with a microbiota from conventionally raised mice modified the neuroanatomy of the ENS and increased intestinal transit rates, which was associated with neuronal and mucosal 5-HT production and the proliferation of enteric neuronal progenitors in the adult intestine. Pharmacological modulation of the 5-HT4 receptor, as well as depletion of endogenous 5-HT, identified a mechanistic link between the gut microbiota and maturation of the adult ENS through the release of 5-HT and activation of the 5-HT4 receptor. Taken together, these findings show that the microbiota modulates the anatomy of the adult ENS in a 5-HT-dependent fashion with concomitant changes in intestinal transit.", "doi": "10.1073/pnas.1720017115", "pmid": "29866843", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "1720017115"}, {"db": "pmc", "key": "PMC6016808"}], "notes": [], "created": "2020-01-23T16:19:42.075Z", "modified": "2021-06-21T14:25:16.251Z"}, {"entity": "publication", "iuid": "3c8fdf88b6cb4f11a77fcd2899df2341", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3c8fdf88b6cb4f11a77fcd2899df2341.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3c8fdf88b6cb4f11a77fcd2899df2341"}}, "title": "Expression of ribosomal and actin network proteins and immunochemotherapy resistance in diffuse large B cell lymphoma patients", "authors": [{"family": "Bram Ednersson", "given": "Susanne", "initials": "S"}, {"family": "Stenson", "given": "Martin", "initials": "M"}, {"family": "Stern", "given": "Mimmie", "initials": "M"}, {"family": "Enblad", "given": "Gunilla", "initials": "G"}, {"family": "Fagman", "given": "Henrik", "initials": "H"}, {"family": "Nilsson-Ehle", "given": "Herman", "initials": "H"}, {"family": "Hasselblom", "given": "Sverker", "initials": "S"}, {"family": "Andersson", "given": "Per Ola", "initials": "PO"}], "type": "journal-article", "published": "2018-06-00", "journal": {"volume": "181", "issn": "0007-1048", "issue": "6", "pages": "770-781", "title": "Br J Haematol", "issn-l": "0007-1048"}, "abstract": "Diffuse large B cell lymphoma (DLBCL) patients with early relapse or refractory disease have a very poor outcome. Immunochemotherapy resistance will probably, also in the era of targeted drugs, remain the major cause of treatment failure. We used proteomic mass spectrometry to analyse the global protein expression of micro-dissected formalin-fixed paraffin-embedded tumour tissues from 97 DLBCL patients: 44 with primary refractory disease or relapse within 1 year from diagnosis (REF/REL), and 53 who were progression-free more than 5 years after diagnosis (CURED). We identified 2127 proteins: 442 were found in all patients and 102 were differentially expressed. Sixty-five proteins were overexpressed in REF/REL patients, of which 46 were ribosomal proteins (RPs) compared with 2 of the 37 overexpressed proteins in CURED patients (P = 7\u00b76 \u00d7 10 -10 ). Twenty of 37 overexpressed proteins in CURED patients were associated with actin regulation, compared with 1 of 65 in REF/REL patients (P = 1\u00b74 \u00d7 10-9 ). Immunohistochemical staining showed higher expression of RPS5 and RPL17 in REF/REL patients while MARCKS-like protein, belonging to the actin network, was more highly expressed in CURED patients. Even though functional studies aimed at individual proteins and protein interactions to evaluate potential clinical effect are needed, our findings suggest new mechanisms behind immunochemotherapy resistance in DLBCL.", "doi": "10.1111/bjh.15259", "pmid": "29767447", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service", "Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [], "notes": [], "created": "2020-01-23T16:17:19.560Z", "modified": "2024-01-16T13:46:32.343Z"}, {"entity": "publication", "iuid": "98783fcd568e4f5085d98d1465719950", "links": {"self": {"href": "https://publications.scilifelab.se/publication/98783fcd568e4f5085d98d1465719950.json"}, "display": {"href": "https://publications.scilifelab.se/publication/98783fcd568e4f5085d98d1465719950"}}, "title": "Humanizing Miniature Hearts through 4-Flow Cannulation Perfusion Decellularization and Recellularization.", "authors": [{"family": "Nguyen", "given": "Duong T", "initials": "DT", "orcid": "0000-0002-4700-9067", "researcher": {"href": "https://publications.scilifelab.se/researcher/08e63e8c6a9e47c2b6d3e61e61cf0cc2.json"}}, {"family": "O'Hara", "given": "Matthew", "initials": "M"}, {"family": "Graneli", "given": "Cecilia", "initials": "C"}, {"family": "Hicks", "given": "Ryan", "initials": "R"}, {"family": "Miliotis", "given": "Tasso", "initials": "T"}, {"family": "Nystr\u00f6m", "given": "Ann-Christin", "initials": "AC"}, {"family": "Hansson", "given": "Sara", "initials": "S"}, {"family": "Davidsson", "given": "Pia", "initials": "P"}, {"family": "Gan", "given": "Li-Ming", "initials": "LM"}, {"family": "Magnone", "given": "Maria Chiara", "initials": "MC"}, {"family": "Althage", "given": "Magnus", "initials": "M"}, {"family": "Heydarkhan-Hagvall", "given": "Sepideh", "initials": "S"}], "type": "journal article", "published": "2018-05-10", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "8", "issue": "1", "pages": "7458", "issn-l": "2045-2322"}, "abstract": "Despite improvements in pre-clinical drug testing models, predictability of clinical outcomes continues to be inadequate and costly due to poor evidence of drug metabolism. Humanized miniature organs integrating decellularized rodent organs with tissue specific cells are translational models that can provide further physiological understanding and evidence. Here, we evaluated 4-Flow cannulated rat hearts as the fundamental humanized organ model for cardiovascular drug validation. Results show clearance of cellular components in all chambers in 4-Flow hearts with efficient perfusion into both coronary arteries and cardiac veins. Furthermore, material characterization depicts preserved organization and content of important matrix proteins such as collagens, laminin, and elastin. With access to the complete vascular network, different human cell types were delivered to show spatial distribution and integration into the matrix under perfusion for up to three weeks. The feature of 4-Flow cannulation is the preservation of whole heart conformity enabling ventricular pacing via the pulmonary vein as demonstrated by noninvasive monitoring with fluid pressure and ultrasound imaging. Consequently, 4-Flow hearts surmounting organ mimicry challenges with intact complexity in vasculature and mechanical compliance of the whole organ providing an ideal platform for improving pre-clinical drug validation in addition to understanding cardiovascular diseases.", "doi": "10.1038/s41598-018-25883-x", "pmid": "29748585", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-018-25883-x"}, {"db": "pmc", "key": "PMC5945628"}], "notes": [], "created": "2020-01-23T16:51:37.952Z", "modified": "2021-06-21T13:56:58.378Z"}, {"entity": "publication", "iuid": "c3dcf2e9bf1d4382866d6a7c7b6018f7", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c3dcf2e9bf1d4382866d6a7c7b6018f7.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c3dcf2e9bf1d4382866d6a7c7b6018f7"}}, "title": "The GTPase domain of gamma-tubulin is required for normal mitochondrial function and spatial organization.", "authors": [{"family": "Lindstr\u00f6m", "given": "Lisa", "initials": "L"}, {"family": "Li", "given": "Tongbin", "initials": "T"}, {"family": "Malycheva", "given": "Darina", "initials": "D"}, {"family": "Kancharla", "given": "Arun", "initials": "A"}, {"family": "Nilsson", "given": "Hel\u00e9n", "initials": "H"}, {"family": "Vishnu", "given": "Neelanjan", "initials": "N"}, {"family": "Mulder", "given": "Hindrik", "initials": "H"}, {"family": "Johansson", "given": "Martin", "initials": "M"}, {"family": "Rossell\u00f3", "given": "Catalina Ana", "initials": "CA"}, {"family": "Alvarado-Kristensson", "given": "Maria", "initials": "M", "orcid": "0000-0003-0598-7986", "researcher": {"href": "https://publications.scilifelab.se/researcher/70ee81797eff452fa037821f293d8673.json"}}], "type": "journal article", "published": "2018-05-03", "journal": {"title": "Commun Biol", "issn": "2399-3642", "volume": "1", "issue": "1", "pages": "37", "issn-l": "2399-3642"}, "abstract": "In the cell, \u03b3-tubulin establishes a cellular network of threads named the \u03b3-string meshwork. However, the functions of this meshwork remain to be determined. We investigated the traits of the meshwork and show that \u03b3-strings have the ability to connect the cytoplasm and the mitochondrial DNA together. We also show that \u03b3-tubulin has a role in the maintenance of the mitochondrial network and functions as reduced levels of \u03b3-tubulin or impairment of its GTPase domain disrupts the mitochondrial network and alters both their respiratory capacity and the expression of mitochondrial-related genes. By contrast, reduced mitochondrial number or increased protein levels of \u03b3-tubulin DNA-binding domain enhanced the association of \u03b3-tubulin with mitochondria. Our results demonstrate that \u03b3-tubulin is an important mitochondrial structural component that maintains the mitochondrial network, providing mitochondria with a cellular infrastructure. We propose that \u03b3-tubulin provides a cytoskeletal element that gives form to the mitochondrial network.", "doi": "10.1038/s42003-018-0037-3", "pmid": "30271923", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service", "National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s42003-018-0037-3"}, {"db": "pmc", "key": "PMC6123723"}], "notes": [], "created": "2020-01-23T16:26:11.434Z", "modified": "2021-11-03T15:41:13.583Z"}, {"entity": "publication", "iuid": "503f30b2eb6b40a799fa2e8925f72081", "links": {"self": {"href": "https://publications.scilifelab.se/publication/503f30b2eb6b40a799fa2e8925f72081.json"}, "display": {"href": "https://publications.scilifelab.se/publication/503f30b2eb6b40a799fa2e8925f72081"}}, "title": "Uterine progesterone signaling is a target for metformin therapy in PCOS-like rats.", "authors": [{"family": "Hu", "given": "Min", "initials": "M"}, {"family": "Zhang", "given": "Yuehui", "initials": "Y"}, {"family": "Feng", "given": "Jiaxing", "initials": "J"}, {"family": "Xu", "given": "Xue", "initials": "X"}, {"family": "Zhang", "given": "Jiao", "initials": "J"}, {"family": "Zhao", "given": "Wei", "initials": "W"}, {"family": "Guo", "given": "Xiaozhu", "initials": "X"}, {"family": "Li", "given": "Juan", "initials": "J"}, {"family": "Vestin", "given": "Edvin", "initials": "E"}, {"family": "Cui", "given": "Peng", "initials": "P"}, {"family": "Li", "given": "Xin", "initials": "X"}, {"family": "Wu", "given": "Xiao-Ke", "initials": "XK"}, {"family": "Br\u00e4nnstr\u00f6m", "given": "Mats", "initials": "M"}, {"family": "Shao", "given": "Linus R", "initials": "LR"}, {"family": "Billig", "given": "H\u00e5kan", "initials": "H"}], "type": "journal article", "published": "2018-05-00", "journal": {"volume": "237", "issn": "1479-6805", "issue": "2", "pages": "123-137", "title": "J Endocrinol", "issn-l": null}, "abstract": "Impaired progesterone (P4) signaling is linked to endometrial dysfunction and infertility in women with polycystic ovary syndrome (PCOS). Here, we report for the first time that elevated expression of progesterone receptor (PGR) isoforms A and B parallels increased estrogen receptor (ER) expression in PCOS-like rat uteri. The aberrant PGR-targeted gene expression in PCOS-like rats before and after implantation overlaps with dysregulated expression of Fkbp52 and Ncoa2, two genes that contribute to the development of uterine P4 resistance. In vivo and in vitro studies of the effects of metformin on the regulation of the uterine P4 signaling pathway under PCOS conditions showed that metformin directly inhibits the expression of PGR and ER along with the regulation of several genes that are targeted dependently or independently of PGR-mediated uterine implantation. Functionally, metformin treatment corrected the abnormal expression of cell-specific PGR and ER and some PGR-target genes in PCOS-like rats with implantation. Additionally, we documented how metformin contributes to the regulation of the PGR-associated MAPK/ERK/p38 signaling pathway in the PCOS-like rat uterus. Our data provide novel insights into how metformin therapy regulates uterine P4 signaling molecules under PCOS conditions.", "doi": "10.1530/JOE-18-0086", "pmid": "29535146", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "JOE-18-0086"}], "notes": [], "created": "2020-01-23T16:22:29.558Z", "modified": "2021-06-21T14:27:29.904Z"}, {"entity": "publication", "iuid": "3b356b5d45c644838c7145a377e726c5", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3b356b5d45c644838c7145a377e726c5.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3b356b5d45c644838c7145a377e726c5"}}, "title": "Granule-stored MUC5B mucins are packed by the non-covalent formation of N-terminal head-to-head tetramers.", "authors": [{"family": "Trillo-Muyo", "given": "Sergio", "initials": "S"}, {"family": "Nilsson", "given": "Harriet E", "initials": "HE"}, {"family": "Recktenwald", "given": "Christian V", "initials": "CV"}, {"family": "Ermund", "given": "Anna", "initials": "A"}, {"family": "Ridley", "given": "Caroline", "initials": "C"}, {"family": "Meiss", "given": "Lauren N", "initials": "LN"}, {"family": "B\u00e4hr", "given": "Andrea", "initials": "A"}, {"family": "Klymiuk", "given": "Nikolai", "initials": "N"}, {"family": "Wine", "given": "Jeffrey J", "initials": "JJ"}, {"family": "Koeck", "given": "Philip J B", "initials": "PJB"}, {"family": "Thornton", "given": "David J", "initials": "DJ"}, {"family": "Hebert", "given": "Hans", "initials": "H"}, {"family": "Hansson", "given": "Gunnar C", "initials": "GC"}], "type": "journal article", "published": "2018-04-13", "journal": {"title": "J. Biol. Chem.", "issn": "1083-351X", "volume": "293", "issue": "15", "pages": "5746-5754", "issn-l": "0021-9258"}, "abstract": "Most MUC5B mucin polymers in the upper airways of humans and pigs are produced by submucosal glands. MUC5B forms N-terminal covalent dimers that are further packed into larger assemblies because of low pH and high Ca 2+ in the secretory granule of the mucin-producing cell. We purified the recombinant MUC5B N-terminal covalent dimer and used single-particle electron microscopy to study its structure under intracellular conditions. We found that, at intragranular pH, the dimeric MUC5B organized into head-to-head noncovalent tetramers where the von Willebrand D1-D2 domains hooked into each other. These N-terminal tetramers further formed long linear complexes from which, we suggest, the mucin domains and their C termini project radially outwards. Using conventional and video microscopy, we observed that, upon secretion into the submucosal gland ducts, a flow of bicarbonate-rich fluid passes the mucin-secreting cells. We suggest that this unfolds and pulls out the MUC5B assemblies into long linear threads. These further assemble into thicker mucin bundles in the glandular ducts before emerging at the gland duct opening. We conclude that the combination of intracellular packing of the MUC5B mucin and the submucosal gland morphology creates an efficient machine for producing linear mucin bundles.", "doi": "10.1074/jbc.RA117.001014", "pmid": "29440393", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S0021-9258(20)41867-8"}, {"db": "pmc", "key": "PMC5900763"}], "notes": [], "created": "2020-01-23T16:32:15.964Z", "modified": "2021-06-21T14:29:11.771Z"}, {"entity": "publication", "iuid": "99256f2660b146e589a8e734ce7e0fe2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/99256f2660b146e589a8e734ce7e0fe2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/99256f2660b146e589a8e734ce7e0fe2"}}, "title": "Abundant fish protein inhibits \u03b1-synuclein amyloid formation.", "authors": [{"family": "Werner", "given": "Tony", "initials": "T"}, {"family": "Kumar", "given": "Ranjeet", "initials": "R"}, {"family": "Horvath", "given": "Istvan", "initials": "I"}, {"family": "Scheers", "given": "Nathalie", "initials": "N", "orcid": "0000-0001-8812-9025", "researcher": {"href": "https://publications.scilifelab.se/researcher/247e0ccd008f4795af5d666a181269b5.json"}}, {"family": "Wittung-Stafshede", "given": "Pernilla", "initials": "P", "orcid": "0000-0003-1058-1964", "researcher": {"href": "https://publications.scilifelab.se/researcher/9016aa00d62f439fb15532a1f4ba814e.json"}}], "type": "journal article", "published": "2018-04-03", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "8", "issue": "1", "pages": "5465", "issn-l": "2045-2322"}, "abstract": "The most common allergen in fish, the highly-abundant protein \u03b2-parvalbumin, forms amyloid structures as a way to avoid gastrointestinal degradation and transit to the blood. In humans, the same amyloid structures are mostly associated with neurodegenerative disorders such as Alzheimer's and Parkinson's. We here assessed a putative connection between these amyloids using recombinant Atlantic cod \u03b2-parvalbumin and the key amyloidogenic protein in Parkinson's disease, \u03b1-synuclein. Using a set of in vitro biophysical methods, we discovered that \u03b2-parvalbumin readily inhibits amyloid formation of \u03b1-synuclein. The underlying mechanism was found to involve \u03b1-synuclein binding to the surface of \u03b2-parvalbumin amyloid fibers. In addition to being a new amyloid inhibition mechanism, the data suggest that health benefits of fish may be explained in part by cross-reaction of \u03b2-parvalbumin with human amyloidogenic proteins.", "doi": "10.1038/s41598-018-23850-0", "pmid": "29615738", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-018-23850-0"}, {"db": "pmc", "key": "PMC5882657"}], "notes": [], "created": "2020-01-23T16:33:32.278Z", "modified": "2021-06-21T13:56:47.848Z"}, {"entity": "publication", "iuid": "2b84f4b963034427ad4f251e523be761", "links": {"self": {"href": "https://publications.scilifelab.se/publication/2b84f4b963034427ad4f251e523be761.json"}, "display": {"href": "https://publications.scilifelab.se/publication/2b84f4b963034427ad4f251e523be761"}}, "title": "The neuroendocrine phenotype, genomic profile and therapeutic sensitivity of GEPNET cell lines. Correction", "authors": [{"family": "Hofving", "given": "Tobias", "initials": "T"}, {"family": "Arvidsson", "given": "Yvonne", "initials": "Y"}, {"family": "Almobarak", "given": "Bilal", "initials": "B"}, {"family": "Inge", "given": "Linda", "initials": "L"}, {"family": "Pfragner", "given": "Roswitha", "initials": "R"}, {"family": "Persson", "given": "Marta", "initials": "M"}, {"family": "Stenman", "given": "G\u00f6ran", "initials": "G"}, {"family": "Kristiansson", "given": "Erik", "initials": "E"}, {"family": "Johanson", "given": "Viktor", "initials": "V"}, {"family": "Nilsson", "given": "Ola", "initials": "O"}], "type": "journal-article", "published": "2018-04-00", "journal": {"volume": "25", "issn": "1351-0088", "issue": "4", "pages": "X1-X2", "title": "Endocr Relat Cancer", "issn-l": null}, "abstract": null, "doi": "10.1530/erc-17-0445e", "pmid": "29540494", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2020-01-23T16:21:37.543Z", "modified": "2021-05-24T15:37:29.270Z"}, {"entity": "publication", "iuid": "12492e542a514f7a98c073b00e84ff9d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/12492e542a514f7a98c073b00e84ff9d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/12492e542a514f7a98c073b00e84ff9d"}}, "title": "Effects of fixation on electrophysiology and structure of human jejunal villi.", "authors": [{"family": "Casselbrant", "given": "Anna", "initials": "A", "orcid": "0000-0001-7514-7435", "researcher": {"href": "https://publications.scilifelab.se/researcher/994b2b65cd154b359f5228eb0c69828b.json"}}, {"family": "Helander", "given": "Herbert F", "initials": "HF"}], "type": "journal article", "published": "2018-04-00", "journal": {"title": "Microsc Res Tech", "issn": "1097-0029", "volume": "81", "issue": "4", "pages": "376-383", "issn-l": "1059-910X"}, "abstract": "The villi of human jejunum vary in size and shape during different functional conditions. In the base the lamina propria is isotonic with blood, in the tip hyperosmotic. Here we study electrophysiological and morphological effects of incubation in hypotonic, isotonic, or hypertonic solutions, and to test various isotonic fixatives for microscopy. Samples of jejunal mucosae, obtained during surgery in obese patients, were studied in Ussing chambers where electrical parameters were registered during incubation in Krebs solution at various osmolarities, and during fixation in formaldehyde, glutaraldehyde, or osmium tetroxide (OsO 4 ). The same fixatives were used for other jejunal specimens that were fixed directly for light microscopy. Morphometry was carried out to determine size and height of villi, proportion of lamina propria, and surface enlargement due to villi. Ussing chamber incubation in fluids with low osmolarity resulted in increased electrical resistance and epithelial swelling. Opposite results were obtained at high osmolality. Fixation was faster in formaldehyde than in glutaraldehyde or OsO4 . In biopsies processed directly for light microscopy the proportions of lamina propria of the mucosa, and of lamina propria of villi, were significantly larger in biopsies fixed in formaldehyde than after fixation in glutaraldehyde or OsO4 . The villus tips sometimes ended with a bleb with prominent spaces between the epithelial cells. In summary, jejunal villi swell in vitro when exposed to hypotonic solutions, and shrink in hypertonic solutions. Much of the morphological changes occurring during fixation can be related to the physiological hyperosmolar milieu in villus tips.", "doi": "10.1002/jemt.22988", "pmid": "29322584", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2020-01-23T16:18:00.732Z", "modified": "2021-06-21T14:29:33.036Z"}, {"entity": "publication", "iuid": "318bfeaef13a4c66999ad19c817f92ae", "links": {"self": {"href": "https://publications.scilifelab.se/publication/318bfeaef13a4c66999ad19c817f92ae.json"}, "display": {"href": "https://publications.scilifelab.se/publication/318bfeaef13a4c66999ad19c817f92ae"}}, "title": "The neuroendocrine phenotype, genomic profile and therapeutic sensitivity of GEPNET cell lines.", "authors": [{"family": "Hofving", "given": "Tobias", "initials": "T"}, {"family": "Arvidsson", "given": "Yvonne", "initials": "Y"}, {"family": "Almobarak", "given": "Bilal", "initials": "B"}, {"family": "Inge", "given": "Linda", "initials": "L"}, {"family": "Pfragner", "given": "Roswitha", "initials": "R"}, {"family": "Persson", "given": "Marta", "initials": "M"}, {"family": "Stenman", "given": "G\u00f6ran", "initials": "G"}, {"family": "Kristiansson", "given": "Erik", "initials": "E"}, {"family": "Johanson", "given": "Viktor", "initials": "V"}, {"family": "Nilsson", "given": "Ola", "initials": "O"}], "type": "journal article", "published": "2018-03-00", "journal": {"volume": "25", "issn": "1479-6821", "issue": "3", "pages": "367-380", "title": "Endocr. Relat. Cancer", "issn-l": "1351-0088"}, "abstract": "Experimental models of neuroendocrine tumour disease are scarce, and no comprehensive characterisation of existing gastroenteropancreatic neuroendocrine tumour (GEPNET) cell lines has been reported. In this study, we aimed to define the molecular characteristics and therapeutic sensitivity of these cell lines. We therefore performed immunophenotyping, copy number profiling, whole-exome sequencing and a large-scale inhibitor screening of seven GEPNET cell lines. Four cell lines, GOT1, P-STS, BON-1 and QGP-1, displayed a neuroendocrine phenotype while three others, KRJ-I, L-STS and H-STS, did not. Instead, these three cell lines were identified as lymphoblastoid. Characterisation of remaining authentic GEPNET cell lines by copy number profiling showed that GOT1, among other chromosomal alterations, harboured losses on chromosome 18 encompassing the SMAD4 gene, while P-STS had a loss on 11q. BON-1 had a homozygous loss of CDKN2A and CDKN2B, and QGP-1 harboured amplifications of MDM2 and HMGA2 Whole-exome sequencing revealed both disease-characteristic mutations (e.g. ATRX mutation in QGP-1) and, for patient tumours, rare genetic events (e.g. TP53 mutation in P-STS, BON-1 and QGP-1). A large-scale inhibitor screening showed that cell lines from pancreatic NETs to a greater extent, when compared to small intestinal NETs, were sensitive to inhibitors of MEK. Similarly, neuroendocrine NET cells originating from the small intestine were considerably more sensitive to a group of HDAC inhibitors. Taken together, our results provide a comprehensive characterisation of GEPNET cell lines, demonstrate their relevance as neuroendocrine tumour models and explore their therapeutic sensitivity to a broad range of inhibitors.", "doi": "10.1530/ERC-17-0445", "pmid": "29444910", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "25/3/367"}, {"db": "pmc", "key": "PMC5827037"}], "notes": [], "created": "2020-01-23T16:50:26.664Z", "modified": "2021-07-05T14:11:12.407Z"}, {"entity": "publication", "iuid": "093c9af07c42451d9a937b855507d4b4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/093c9af07c42451d9a937b855507d4b4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/093c9af07c42451d9a937b855507d4b4"}}, "title": "Mesenchymal stem cell-derived exosomes have altered microRNA profiles and induce osteogenic differentiation depending on the stage of differentiation.", "authors": [{"family": "Wang", "given": "Xiaoqin", "initials": "X"}, {"family": "Omar", "given": "Omar", "initials": "O"}, {"family": "Vazirisani", "given": "Forugh", "initials": "F"}, {"family": "Thomsen", "given": "Peter", "initials": "P"}, {"family": "Ekstr\u00f6m", "given": "Karin", "initials": "K", "orcid": "0000-0001-7808-4572", "researcher": {"href": "https://publications.scilifelab.se/researcher/d1922e7379bb4a5ca81b7db180a2d694.json"}}], "type": "journal article", "published": "2018-02-15", "journal": {"title": "PLoS ONE", "issn": "1932-6203", "volume": "13", "issue": "2", "pages": "e0193059", "issn-l": "1932-6203"}, "abstract": "Human mesenchymal stem cell (hMSC)-derived exosomes have shown regenerative effects, but their role in osteogenesis and the underlying mechanism are yet to be determined. In this study, we examined the time-course secretion of exosomes by hMSCs during the entire process of osteogenic differentiation. Exosomes derived from hMSCs in various stages of osteogenic differentiation committed homotypic cells to differentiate towards osteogenic lineage, but only exosomes from late stages of osteogenic differentiation induced extracellular matrix mineralisation. Exosomes from expansion and early and late stages of osteogenic differentiation were internalised by a subpopulation of hMSCs. MicroRNA profiling revealed a set of differentially expressed exosomal microRNAs from the late stage of osteogenic differentiation, which were osteogenesis related. Target prediction demonstrated that these microRNAs enriched pathways involved in regulation of osteogenic differentiation and general mechanisms how exosomes exert their functions, such as \"Wnt signalling pathway\" and \"endocytosis\". Taken together, the results show that MSCs secrete exosomes with different biological properties depending on differentiation stage of their parent cells. The exosomal cargo transferred from MSCs in the late stage of differentiation induces osteogenic differentiation and mineralisation. Moreover, it is suggested that the regulatory effect on osteogenesis by exosomes is at least partly exerted by exosomal microRNA.", "doi": "10.1371/journal.pone.0193059", "pmid": "29447276", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "PONE-D-17-34946"}, {"db": "pmc", "key": "PMC5814093"}], "notes": [], "created": "2020-01-23T16:33:13.303Z", "modified": "2021-06-21T14:32:23.361Z"}, {"entity": "publication", "iuid": "c19d0b311f484e0ba069594f3057e7cf", "links": {"self": {"href": "https://publications.scilifelab.se/publication/c19d0b311f484e0ba069594f3057e7cf.json"}, "display": {"href": "https://publications.scilifelab.se/publication/c19d0b311f484e0ba069594f3057e7cf"}}, "title": "Bifidobacteria or Fiber Protects against Diet-Induced Microbiota-Mediated Colonic Mucus Deterioration.", "authors": [{"family": "Schroeder", "given": "Bjoern O", "initials": "BO"}, {"family": "Birchenough", "given": "George M H", "initials": "GMH"}, {"family": "St\u00e5hlman", "given": "Marcus", "initials": "M"}, {"family": "Arike", "given": "Liisa", "initials": "L"}, {"family": "Johansson", "given": "Malin E V", "initials": "MEV"}, {"family": "Hansson", "given": "Gunnar C", "initials": "GC"}, {"family": "B\u00e4ckhed", "given": "Fredrik", "initials": "F"}], "type": "journal article", "published": "2018-01-10", "journal": {"title": "Cell Host Microbe", "issn": "1934-6069", "volume": "23", "issue": "1", "pages": "27-40.e7", "issn-l": "1931-3128"}, "abstract": "Diet strongly affects gut microbiota composition, and gut bacteria can influence the colonic mucus layer, a physical barrier that separates trillions of gut bacteria from the host. However, the interplay between a Western style diet (WSD), gut microbiota composition, and the intestinal mucus layer is less clear. Here we show that mice fed a WSD have an altered colonic microbiota composition that causes increased penetrability and a reduced growth rate of the inner mucus layer. Both barrier defects can be prevented by transplanting microbiota from chow-fed mice. In addition, we found that administration of Bifidobacterium longum was sufficient to restore mucus growth, whereas administration of the fiber inulin prevented increased mucus penetrability in WSD-fed mice. We hypothesize that the presence of distinct bacteria is crucial for proper mucus function. If confirmed in humans, these findings may help to better understand diseases with an affected mucus layer, such as ulcerative colitis.", "doi": "10.1016/j.chom.2017.11.004", "pmid": "29276171", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S1931-3128(17)30498-5"}, {"db": "pmc", "key": "PMC5764785"}, {"db": "mid", "key": "NIHMS920472"}], "notes": [], "created": "2020-01-23T16:31:09.135Z", "modified": "2021-06-21T14:46:57.506Z"}, {"entity": "publication", "iuid": "6993625021ef45fca7345fd78444d924", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6993625021ef45fca7345fd78444d924.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6993625021ef45fca7345fd78444d924"}}, "title": "Characterization of gamma-tubulin filaments in mammalian cells.", "authors": [{"family": "Lindstr\u00f6m", "given": "Lisa", "initials": "L"}, {"family": "Alvarado-Kristensson", "given": "Maria", "initials": "M"}], "type": "journal article", "published": "2018-01-00", "journal": {"title": "Biochimica et Biophysica Acta (BBA) - Molecular Cell Research", "issn": "0167-4889", "volume": "1865", "issue": "1", "pages": "158-171", "issn-l": null}, "abstract": "Overexpression of \u03b3-tubulin leads to the formation of filaments, but nothing is known about such filaments with regard to possible presence in cells, structure and probable dynamics. Here, we used mammalian cell lines to investigate the ability of \u03b3-tubulin to form filaments. We found that \u03b3-tubulin produces fibers called \u03b3-tubules in a GTP-dependent manner and that \u03b3-tubules are made up of pericentrin and the \u03b3-tubulin complex proteins 2, 3, 5 and 6. Furthermore, we noted that the number of cells with cytosolic \u03b3-tubules is increased in non-dividing cells. Our experiments showed that \u03b3-tubules are polar structures that have a low regrowth rate compared to microtubules. Also, we observed that \u03b3-tubules were disassembled by treatment with cold, colcemid, citral dimethyl acetal, dimethyl fumarate or mutation of \u03b3-tubulin GTPase domain, but were increased in number by treatment with taxol or by stable expression of the \u03b3-tubulin 1-333 GTPase domain. Our results demonstrate that \u03b3-tubulin forms filaments, and such assembly is facilitated by the GTPase domain of \u03b3-tubulin.", "doi": "10.1016/j.bbamcr.2017.10.008", "pmid": "29050966", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S0167-4889(17)30283-5"}], "notes": [], "created": "2020-01-23T16:35:22.821Z", "modified": "2021-06-21T14:48:03.639Z"}, {"entity": "publication", "iuid": "ea6804e42c5e4575803e5bfb736058af", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ea6804e42c5e4575803e5bfb736058af.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ea6804e42c5e4575803e5bfb736058af"}}, "title": "Low-dose \u03b3-secretase inhibition increases secretion of A\u03b2 peptides and intracellular oligomeric A\u03b2.", "authors": [{"family": "Agholme", "given": "Lotta", "initials": "L", "orcid": "0000-0003-3816-7474", "researcher": {"href": "https://publications.scilifelab.se/researcher/a7034ae6b9644a6fabd3bfb6d719459b.json"}}, {"family": "Clarin", "given": "Marcus", "initials": "M"}, {"family": "Gkanatsiou", "given": "Eleni", "initials": "E", "orcid": "0000-0003-4443-2836", "researcher": {"href": "https://publications.scilifelab.se/researcher/021f4c0da3ee408999103c7504e39170.json"}}, {"family": "Kettunen", "given": "Petronella", "initials": "P"}, {"family": "Chebli", "given": "Jasmine", "initials": "J"}, {"family": "Brinkmalm", "given": "Gunnar", "initials": "G"}, {"family": "Blennow", "given": "Kaj", "initials": "K"}, {"family": "Bergstr\u00f6m", "given": "Petra", "initials": "P"}, {"family": "Portelius", "given": "Erik", "initials": "E"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H"}], "type": "journal article", "published": "2017-12-00", "journal": {"title": "Molecular and Cellular Neuroscience", "issn": "1095-9327", "volume": "85", "issue": null, "pages": "211-219", "issn-l": "1044-7431"}, "abstract": "\u03b3-Secretase inhibitors have been considered promising drug candidates against Alzheimer's disease (AD) due to their ability to reduce amyloid-\u03b2 (A\u03b2) production. However, clinical trials have been halted due to lack of clinical efficacy and/or side effects. Recent in vitro studies suggest that low doses of \u03b3-secretase inhibitors may instead increase A\u03b2 production. Using a stem cell-derived human model of cortical neurons and low doses of the \u03b3-secretase inhibitor DAPT, the effects on a variety of A\u03b2 peptides were studied using mass spectrometry. One major focus was to develop a novel method for specific detection of oligomeric A\u03b2 (oA\u03b2), and this was used to study the effects of low-dose \u03b3-secretase inhibitor treatment on intracellular oA\u03b2 accumulation. Low-dose treatment (2 and 20nM) with DAPT increased the secretion of several A\u03b2 peptides, especially A\u03b2x-42. Furthermore, using the novel method for oA\u03b2 detection, we found that 2nM DAPT treatment of cortical neurons resulted in increased oA\u03b2 accumulation. Thus, low dose-treatment with DAPT causes both increased production of long, aggregation-prone A\u03b2 peptides and accumulation of intracellular A\u03b2 oligomers, both believed to contribute to AD pathology.", "doi": "10.1016/j.mcn.2017.10.009", "pmid": "29104140", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S1044-7431(16)30246-9"}], "notes": [], "created": "2020-01-23T16:33:43.558Z", "modified": "2021-06-21T14:57:52.544Z"}, {"entity": "publication", "iuid": "332dcd3609654bd8ae8d83a41b357d40", "links": {"self": {"href": "https://publications.scilifelab.se/publication/332dcd3609654bd8ae8d83a41b357d40.json"}, "display": {"href": "https://publications.scilifelab.se/publication/332dcd3609654bd8ae8d83a41b357d40"}}, "title": "Extracellular vesicles from human pancreatic islets suppress human islet amyloid polypeptide amyloid formation.", "authors": [{"family": "Ribeiro", "given": "Diana", "initials": "D"}, {"family": "Horvath", "given": "Istvan", "initials": "I"}, {"family": "Heath", "given": "Nikki", "initials": "N"}, {"family": "Hicks", "given": "Ryan", "initials": "R"}, {"family": "Forsl\u00f6w", "given": "Anna", "initials": "A"}, {"family": "Wittung-Stafshede", "given": "Pernilla", "initials": "P", "orcid": "0000-0003-1058-1964", "researcher": {"href": "https://publications.scilifelab.se/researcher/9016aa00d62f439fb15532a1f4ba814e.json"}}], "type": "journal article", "published": "2017-10-17", "journal": {"title": "Proc. Natl. Acad. Sci. U.S.A.", "issn": "1091-6490", "volume": "114", "issue": "42", "pages": "11127-11132", "issn-l": "0027-8424"}, "abstract": "Extracellular vesicles (EVs) are small vesicles released by cells to aid cell-cell communication and tissue homeostasis. Human islet amyloid polypeptide (IAPP) is the major component of amyloid deposits found in pancreatic islets of patients with type 2 diabetes (T2D). IAPP is secreted in conjunction with insulin from pancreatic \u03b2 cells to regulate glucose metabolism. Here, using a combination of analytical and biophysical methods in vitro, we tested whether EVs isolated from pancreatic islets of healthy patients and patients with T2D modulate IAPP amyloid formation. We discovered that pancreatic EVs from healthy patients reduce IAPP amyloid formation by peptide scavenging, but T2D pancreatic and human serum EVs have no effect. In accordance with these differential effects, the insulin:C-peptide ratio and lipid composition differ between EVs from healthy pancreas and EVs from T2D pancreas and serum. It appears that healthy pancreatic EVs limit IAPP amyloid formation via direct binding as a tissue-specific control mechanism.", "doi": "10.1073/pnas.1711389114", "pmid": "28973954", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "1711389114"}, {"db": "pmc", "key": "PMC5651775"}], "notes": [], "created": "2020-01-23T16:35:56.086Z", "modified": "2021-06-21T15:04:31.335Z"}, {"entity": "publication", "iuid": "ade35766ffb54a9d97b0dc19bdc77cd8", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ade35766ffb54a9d97b0dc19bdc77cd8.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ade35766ffb54a9d97b0dc19bdc77cd8"}}, "title": "Delivery of cyclodextrin polymers to bacterial biofilms - An exploratory study using rhodamine labelled cyclodextrins and multiphoton microscopy.", "authors": [{"family": "Thomsen", "given": "Hanna", "initials": "H"}, {"family": "Benkovics", "given": "G\u00e1bor", "initials": "G"}, {"family": "Fenyvesi", "given": "\u00c9va", "initials": "\u00c9"}, {"family": "Farewell", "given": "Anne", "initials": "A"}, {"family": "Malanga", "given": "Milo", "initials": "M"}, {"family": "Ericson", "given": "Marica B", "initials": "MB"}], "type": "journal article", "published": "2017-10-15", "journal": {"title": "Int J Pharm", "issn": "1873-3476", "volume": "531", "issue": "2", "pages": "650-657", "issn-l": "0378-5173"}, "abstract": "Cyclodextrin (CD) polymers are interesting nanoparticulate systems for pharmaceutical delivery; however, knowledge regarding their applications towards delivery into complex microbial biofilm structures is so far limited. The challenge is to demonstrate penetration and transport through the biofilm and its exopolysaccharide matrix. The ideal functionalization for penetration into mature biofilms is unexplored. In this paper, we present a novel set of rhodamine labelled \u03b2CD-polymers, with different charge moieties, i.e., neutral, anionic, and cationic, and explore their potential delivery into mature Staphylococcus epidermidis biofilms using multiphoton laser scanning microscopy (MPM). The S. epidermidis biofilms, being a medically relevant model organism, were stained with SYTO9. By using MPM, three-dimensional imaging and spectral investigation of the distribution of the \u03b2CD-polymers could be obtained. It was found that the cationic \u03b2CD-polymers showed significantly higher integration into the biofilms, compared to neutral and anionic functionalized \u03b2CDs. None of the carriers presented any inherent toxicity to the biofilms, meaning that the addition of rhodamine moiety does not affect the inertness of the delivery system. Taken together, this study demonstrates a novel approach by which delivery of fluorescently labelled CD nanoparticles to bacterial biofilms can be explored using MPM. Future studies should be undertaken investigating the potential in using cationic functionalization of CD based delivery systems for targeting anti-microbial effects in biofilms.", "doi": "10.1016/j.ijpharm.2017.06.011", "pmid": "28596141", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S0378-5173(17)30519-7"}], "notes": [], "created": "2020-01-23T16:36:43.762Z", "modified": "2021-06-21T15:05:16.862Z"}, {"entity": "publication", "iuid": "3de90d2d26634b8d88e9baaba3bf166b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3de90d2d26634b8d88e9baaba3bf166b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3de90d2d26634b8d88e9baaba3bf166b"}}, "title": "Deficiency in Calcium-Binding Protein S100A4 Impairs the Adjuvant Action of Cholera Toxin.", "authors": [{"family": "Sun", "given": "Jia-Bin", "initials": "JB"}, {"family": "Holmgren", "given": "Jan", "initials": "J"}, {"family": "Larena", "given": "Maximilian", "initials": "M"}, {"family": "Terrinoni", "given": "Manuela", "initials": "M"}, {"family": "Fang", "given": "Yu", "initials": "Y"}, {"family": "Bresnick", "given": "Anne R", "initials": "AR"}, {"family": "Xiang", "given": "Zou", "initials": "Z"}], "type": "journal article", "published": "2017-09-11", "journal": {"title": "Front Immunol", "issn": "1664-3224", "volume": "8", "issue": null, "pages": "1119", "issn-l": "1664-3224"}, "abstract": "The calcium-binding protein S100A4 has been described to promote pathological inflammation in experimental autoimmune and inflammatory disorders and in allergy and to contribute to antigen presentation and antibody response after parenteral immunization with an alum-adjuvanted antigen. In this study, we extend these findings by demonstrating that mice lacking S100A4 have a defective humoral and cellular immune response to mucosal (sublingual) immunization with a model protein antigen [ovalbumin (OVA)] given together with the strong mucosal adjuvant cholera toxin (CT), and that this impairment is due to defective adjuvant-stimulated antigen presentation by antigen-presenting cells. In comparison to wild-type (WT) mice, mice genetically lacking S100A4 had reduced humoral and cellular immune responses after immunization with OVA plus CT, including a complete lack of detectable germinal center reaction. Further, when stimulated in vitro with OVA plus CT, S100A4-/- dendritic cells (DCs) showed impaired responses in several CT-stimulated immune regulatory molecules including the co-stimulatory molecule CD86, inflammasome-associated caspase-1 and IL-1\u03b2. Coculture of OVA-specific OT-II T cells with S100A4-/- DCs that had been pulse incubated with OVA plus CT resulted in impaired OT-II T cell proliferation and reduced production of Th1, Th2, and Th17 cytokines compared to similar cocultures with WT DCs. In accordance with these findings, transfection of WT DCs with S100A4-targeting small interfering RNA (siRNA) but not mock-siRNA resulted in significant reductions in the expression of caspase-1 and IL-1\u03b2 as well as CD86 in response to CT. Importantly, also engraftment of WT DCs into S100A4-/- mice effectively restored the immune response to immunization in the recipients. In conclusion, our results demonstrate that deficiency in S100A4 has a strong impact on the development of both humoral and cellular immunity after mucosal immunization using CT as adjuvant.", "doi": "10.3389/fimmu.2017.01119", "pmid": "28951732", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC5600718"}], "notes": [], "created": "2020-01-23T16:36:26.452Z", "modified": "2021-06-21T15:29:05.152Z"}, {"entity": "publication", "iuid": "9cbb19e653c646618c1f02621a306881", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9cbb19e653c646618c1f02621a306881.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9cbb19e653c646618c1f02621a306881"}}, "title": "The adiponectin receptor AdipoR2 and its Caenorhabditis elegans homolog PAQR-2 prevent membrane rigidification by exogenous saturated fatty acids.", "authors": [{"family": "Devkota", "given": "Ranjan", "initials": "R"}, {"family": "Svensk", "given": "Emma", "initials": "E"}, {"family": "Ruiz", "given": "Mario", "initials": "M"}, {"family": "St\u00e5hlman", "given": "Marcus", "initials": "M"}, {"family": "Bor\u00e9n", "given": "Jan", "initials": "J", "orcid": "0000-0003-0786-8091", "researcher": {"href": "https://publications.scilifelab.se/researcher/1e85f6d287ce4c60a7b35b287efb4f79.json"}}, {"family": "Pilon", "given": "Marc", "initials": "M", "orcid": "0000-0003-3919-2882", "researcher": {"href": "https://publications.scilifelab.se/researcher/d45c4ecf9afe463c971af2de53a770a8.json"}}], "type": "journal article", "published": "2017-09-00", "journal": {"title": "PLoS Genet.", "issn": "1553-7404", "volume": "13", "issue": "9", "pages": "e1007004", "issn-l": "1553-7390"}, "abstract": "Dietary fatty acids can be incorporated directly into phospholipids. This poses a specific challenge to cellular membranes since their composition, hence properties, could greatly vary with different diets. That vast variations in diets are tolerated therefore implies the existence of regulatory mechanisms that monitor and regulate membrane compositions. Here we show that the adiponectin receptor AdipoR2, and its C. elegans homolog PAQR-2, are essential to counter the membrane rigidifying effects of exogenously provided saturated fatty acids. In particular, we use dietary supplements or mutated E. coli as food, together with direct measurements of membrane fluidity and composition, to show that diets containing a high ratio of saturated to monounsaturated fatty acids cause membrane rigidity and lethality in the paqr-2 mutant. We also show that mammalian cells in which AdipoR2 has been knocked-down by siRNA are unable to prevent the membrane-rigidifying effects of palmitic acid. We conclude that the PAQR-2 and AdipoR2 proteins share an evolutionarily conserved function that maintains membrane fluidity in the presence of exogenous saturated fatty acids.", "doi": "10.1371/journal.pgen.1007004", "pmid": "28886012", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "PGENETICS-D-17-01342"}, {"db": "pmc", "key": "PMC5607217"}], "notes": [], "created": "2020-01-23T16:34:44.458Z", "modified": "2021-06-21T15:29:30.012Z"}, {"entity": "publication", "iuid": "3b69e05e11fc40e5ba4d2a38f8e60dda", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3b69e05e11fc40e5ba4d2a38f8e60dda.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3b69e05e11fc40e5ba4d2a38f8e60dda"}}, "title": "Membrane trafficking under the microscope, what new imaging technologies have brought to light", "authors": [{"family": "Fernandez-Rodriguez", "given": "J", "initials": "J", "orcid": "0000-0003-4522-0966", "researcher": {"href": "https://publications.scilifelab.se/researcher/3bd9c743e99d479cb752aeec947acab3.json"}}, {"family": "Nilsson", "given": "T", "initials": "T"}], "type": null, "published": "2017-08-01", "journal": {"volume": "1st Edition", "issn": null, "issue": null, "pages": null, "title": "CRC Press", "issn-l": null}, "abstract": null, "doi": null, "pmid": null, "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2020-01-23T16:38:57.196Z", "modified": "2025-11-17T09:36:50.246Z"}, {"entity": "publication", "iuid": "aac1e4e2d8574eaa8cd182dc2b887297", "links": {"self": {"href": "https://publications.scilifelab.se/publication/aac1e4e2d8574eaa8cd182dc2b887297.json"}, "display": {"href": "https://publications.scilifelab.se/publication/aac1e4e2d8574eaa8cd182dc2b887297"}}, "title": "Site-specific gene expression analysis of implant-near cells in a soft tissue infection model - Application of laser microdissection to study biomaterial-associated infection.", "authors": [{"family": "Svensson", "given": "Sara", "initials": "S"}, {"family": "Trobos", "given": "Margarita", "initials": "M"}, {"family": "Omar", "given": "Omar", "initials": "O"}, {"family": "Thomsen", "given": "Peter", "initials": "P"}], "type": "journal article", "published": "2017-08-00", "journal": {"title": "J. Biomed. Mater. Res.", "issn": "1552-4965", "volume": "105", "issue": "8", "pages": "2210-2217", "issn-l": "1549-3296"}, "abstract": "Analysis of the implant-tissue interface is important for an understanding of the cellular response to biomaterials with different surface characteristics. However, inaccessibility to the site has restricted the detailed evaluation of the tissue surrounding the implant. Laser microdissection enables the isolation of specific cells and tissues for subsequent DNA, RNA, or protein analysis. The present experimental study employed laser microdissection to analyze tissue-specific differences in gene expression in cells around infected or control titanium implants 72 h after subcutaneous implantation in a rat model. Three different tissue zones located 0-800 \u03bcm away from the implant-tissue interface were analyzed. Implant sites challenged with a dose of 10 6 CFU Staphylococcus epidermidis demonstrated higher gene expression of selected markers for inflammation (TNF-\u03b1, IL-6), cell recruitment (MCP-1, IL-8, IL-8 R), infection (TLR2), and tissue remodeling (MMP-9) compared with control implants. Furthermore, the gene expression analysis of the three extracted tissue zones revealed marked spatial differences, depending on the distance to the implant. Control implants continuously induced higher cell gene expression in the implant-tissue interface compared with cells 200-800 \u03bcm away from the implant, whereas the sites inoculated with S. epidermidis resulted in high gene expression further away from the implant as well. In conclusion, this study demonstrates that laser microdissection is an interesting tool, revealing both gene- and site-specific gene expression patterns in the implant-tissue interface. The technique provides an opportunity for detailed molecular dissection of the biological events related to the implant but occurring at different distances from the implant. \u00a9 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2210-2217, 2017.", "doi": "10.1002/jbm.a.36088", "pmid": "28395127", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2020-01-23T16:36:33.854Z", "modified": "2021-06-21T15:33:17.885Z"}, {"entity": "publication", "iuid": "f3a2d64e36bb42668a6ae25c44c3b53e", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f3a2d64e36bb42668a6ae25c44c3b53e.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f3a2d64e36bb42668a6ae25c44c3b53e"}}, "title": "Moderate Expression of SEC16 Increases Protein Secretion by Saccharomyces cerevisiae.", "authors": [{"family": "Bao", "given": "Jichen", "initials": "J"}, {"family": "Huang", "given": "Mingtao", "initials": "M"}, {"family": "Petranovic", "given": "Dina", "initials": "D"}, {"family": "Nielsen", "given": "Jens", "initials": "J", "orcid": "0000-0002-9955-6003", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a596e289be4438a8a2653b1f25fea8b.json"}}], "type": "journal article", "published": "2017-07-15", "journal": {"title": "Appl. Environ. Microbiol.", "issn": "1098-5336", "volume": "83", "issue": "14", "pages": null, "issn-l": "0099-2240"}, "abstract": "The yeast Saccharomyces cerevisiae is widely used to produce biopharmaceutical proteins. However, the limited capacity of the secretory pathway may reduce its productivity. Here, we increased the secretion of a heterologous \u03b1-amylase, a model protein used for studying the protein secretory pathway in yeast, by moderately overexpressing SEC16, which is involved in protein translocation from the endoplasmic reticulum to the Golgi apparatus. The moderate overexpression of SEC16 increased \u03b1-amylase secretion by generating more endoplasmic reticulum exit sites. The production of reactive oxygen species resulting from the heterologous \u03b1-amylase production was reduced. A genome-wide expression analysis indicated decreased endoplasmic reticulum stress in the strain that moderately overexpressed SEC16, which was consistent with a decreased volume of the endoplasmic reticulum. Additionally, fewer mitochondria were observed. Finally, the moderate overexpression of SEC16 was shown to improve the secretion of two other recombinant proteins, Trichoderma reesei endoglucanase I and Rhizopus oryzae glucan-1,4-\u03b1-glucosidase, indicating that this mechanism is of general relevance.IMPORTANCE There is an increasing demand for recombinant proteins to be used as enzymes and pharmaceuticals. The yeast Saccharomyces cerevisiae is a cell factory that is widely used to produce recombinant proteins. Our study revealed that moderate overexpression of SEC16 increased recombinant protein secretion in S. cerevisiae This new strategy can be combined with other targets to engineer cell factories to efficiently produce protein in the future.", "doi": "10.1128/AEM.03400-16", "pmid": "28476767", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "AEM.03400-16"}, {"db": "pmc", "key": "PMC5494634"}], "notes": [], "created": "2020-01-23T16:33:54.617Z", "modified": "2021-07-05T13:05:37.790Z"}, {"entity": "publication", "iuid": "58ac3a28707245c785c96dd26ae5d18c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/58ac3a28707245c785c96dd26ae5d18c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/58ac3a28707245c785c96dd26ae5d18c"}}, "title": "Injury Leads to the Appearance of Cells with Characteristics of Both Microglia and Astrocytes in Mouse and Human Brain.", "authors": [{"family": "Wilhelmsson", "given": "Ulrika", "initials": "U"}, {"family": "Andersson", "given": "Daniel", "initials": "D"}, {"family": "de Pablo", "given": "Yolanda", "initials": "Y"}, {"family": "Pekny", "given": "Roy", "initials": "R"}, {"family": "St\u00e5hlberg", "given": "Anders", "initials": "A"}, {"family": "Mulder", "given": "Jan", "initials": "J"}, {"family": "Mitsios", "given": "Nicholas", "initials": "N"}, {"family": "Hortob\u00e1gyi", "given": "Tibor", "initials": "T"}, {"family": "Pekny", "given": "Milos", "initials": "M"}, {"family": "Pekna", "given": "Marcela", "initials": "M"}], "type": "journal article", "published": "2017-06-01", "journal": {"volume": "27", "issn": "1460-2199", "issue": "6", "pages": "3360-3377", "title": "Cereb. Cortex", "issn-l": "1047-3211"}, "abstract": "Microglia and astrocytes have been considered until now as cells with very distinct identities. Here, we assessed the heterogeneity within microglia/monocyte cell population in mouse hippocampus and determined their response to injury, by using single-cell gene expression profiling of cells isolated from uninjured and deafferented hippocampus. We found that in individual cells, microglial markers Cx3cr1, Aif1, Itgam, and Cd68 were co-expressed. Interestingly, injury led to the co-expression of the astrocyte marker Gfap in a subpopulation of Cx3cr1-expressing cells from both the injured and contralesional hippocampus. Cells co-expressing astrocyte and microglia markers were also detected in the in vitro LPS activation/injury model and in sections from human brain affected by stroke, Alzheimer's disease, and Lewy body dementia. Our findings indicate that injury and chronic neurodegeneration lead to the appearance of cells that share molecular characteristics of both microglia and astrocytes, 2 cell types with distinct embryologic origin and function.", "doi": "10.1093/cercor/bhx069", "pmid": "28398520", "labels": {"Fluorescence Tissue Profiling": "Collaborative", "Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "3111278"}], "notes": [], "created": "2017-10-30T14:57:53.920Z", "modified": "2021-05-24T15:37:29.389Z"}, {"entity": "publication", "iuid": "40f9f3fc1b444b0e93af1e0487695f12", "links": {"self": {"href": "https://publications.scilifelab.se/publication/40f9f3fc1b444b0e93af1e0487695f12.json"}, "display": {"href": "https://publications.scilifelab.se/publication/40f9f3fc1b444b0e93af1e0487695f12"}}, "title": "PDE2A2 regulates mitochondria morphology and apoptotic cell death via local modulation of cAMP/PKA signalling.", "authors": [{"family": "Monterisi", "given": "Stefania", "initials": "S", "orcid": "0000-0002-8802-9742", "researcher": {"href": "https://publications.scilifelab.se/researcher/3b139738d17449fc9a91465d3e5ad9cc.json"}}, {"family": "Lobo", "given": "Miguel J", "initials": "MJ"}, {"family": "Livie", "given": "Craig", "initials": "C"}, {"family": "Castle", "given": "John C", "initials": "JC", "orcid": "0000-0002-6017-7794", "researcher": {"href": "https://publications.scilifelab.se/researcher/8da2f3d0e8e448b1ad6b2c090db980c6.json"}}, {"family": "Weinberger", "given": "Michael", "initials": "M"}, {"family": "Baillie", "given": "George", "initials": "G"}, {"family": "Surdo", "given": "Nicoletta C", "initials": "NC"}, {"family": "Musheshe", "given": "Nshunge", "initials": "N"}, {"family": "Stangherlin", "given": "Alessandra", "initials": "A", "orcid": "0000-0001-7296-1183", "researcher": {"href": "https://publications.scilifelab.se/researcher/e6b0df4758a140ccad8bf23cd15f85ea.json"}}, {"family": "Gottlieb", "given": "Eyal", "initials": "E"}, {"family": "Maizels", "given": "Rory", "initials": "R"}, {"family": "Bortolozzi", "given": "Mario", "initials": "M", "orcid": "0000-0001-7198-9838", "researcher": {"href": "https://publications.scilifelab.se/researcher/35b1c39a3d1d43608e14d7eba3107ca2.json"}}, {"family": "Micaroni", "given": "Massimo", "initials": "M"}, {"family": "Zaccolo", "given": "Manuela", "initials": "M", "orcid": "0000-0002-0934-3662", "researcher": {"href": "https://publications.scilifelab.se/researcher/959c5abbe3ec4af4adb37d5549ba2d5c.json"}}], "type": "journal article", "published": "2017-05-02", "journal": {"title": "Elife", "issn": "2050-084X", "volume": "6", "issue": null, "pages": null, "issn-l": "2050-084X"}, "abstract": "cAMP/PKA signalling is compartmentalised with tight spatial and temporal control of signal propagation underpinning specificity of response. The cAMP-degrading enzymes, phosphodiesterases (PDEs), localise to specific subcellular domains within which they control local cAMP levels and are key regulators of signal compartmentalisation. Several components of the cAMP/PKA cascade are located to different mitochondrial sub-compartments, suggesting the presence of multiple cAMP/PKA signalling domains within the organelle. The function and regulation of these domains remain largely unknown. Here, we describe a novel cAMP/PKA signalling domain localised at mitochondrial membranes and regulated by PDE2A2. Using pharmacological and genetic approaches combined with real-time FRET imaging and high resolution microscopy, we demonstrate that in rat cardiac myocytes and other cell types mitochondrial PDE2A2 regulates local cAMP levels and PKA-dependent phosphorylation of Drp1. We further demonstrate that inhibition of PDE2A, by enhancing the hormone-dependent cAMP response locally, affects mitochondria dynamics and protects from apoptotic cell death.", "doi": "10.7554/eLife.21374", "pmid": "28463107", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC5423767"}], "notes": [], "created": "2020-01-23T16:35:40.005Z", "modified": "2021-06-21T15:38:15.280Z"}, {"entity": "publication", "iuid": "b3c2828b051d47ae956b948e54288eb4", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b3c2828b051d47ae956b948e54288eb4.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b3c2828b051d47ae956b948e54288eb4"}}, "title": "Histology-Compatible MALDI Mass Spectrometry Based Imaging of Neuronal Lipids for Subsequent Immunofluorescent Staining.", "authors": [{"family": "Kaya", "given": "Ibrahim", "initials": "I"}, {"family": "Michno", "given": "Wojciech", "initials": "W"}, {"family": "Brinet", "given": "Dimitri", "initials": "D"}, {"family": "Iacone", "given": "Yasmine", "initials": "Y"}, {"family": "Zanni", "given": "Giulia", "initials": "G"}, {"family": "Blennow", "given": "Kaj", "initials": "K"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H"}, {"family": "Hanrieder", "given": "J\u00f6rg", "initials": "J", "orcid": "0000-0001-6059-198X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e65454100674f98bf8f2575093f2441.json"}}], "type": "journal article", "published": "2017-04-18", "journal": {"title": "Anal. Chem.", "issn": "1520-6882", "volume": "89", "issue": "8", "pages": "4685-4694", "issn-l": "0003-2700"}, "abstract": "Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) enables acquisition of spatial distribution maps for molecular species in situ. This can provide comprehensive insights on the pathophysiology of different diseases. However, current sample preparation and MALDI-IMS acquisition methods have limitations in preserving molecular and histological tissue morphology, resulting in interfered correspondence of MALDI-IMS data with subsequently acquired immunofluorescent staining results. We here investigated the histology compatibility of MALDI-IMS to image neuronal lipids in rodent brain tissue with subsequent immunohistochemistry and fluorescent staining of histological features. This was achieved by sublimation of a low ionization energy matrix compound, 1,5-diaminonapthalene (1,5-DAN), minimizing the number of low-energy laser shots. This yielded improved lipid spectral quality and speed of data acquisition and reduced matrix cluster formation along with preservation of specific histological information at cellular levels. This gentle, histology-compatible MALDI-IMS protocol also diminished thermal effects and mechanical stress created during nanosecond laser ablation processes that were prominent in subsequent immunofluorescent staining images but not with classical hematoxylin and eosin (H&E) staining on the same tissue section. Furthermore, this methodology proved to be a powerful strategy for investigating \u03b2-amyloid (A\u03b2) plaque-associated neuronal lipids as exemplified by performing high-resolution MALDI-IMS with subsequent fluorescent amyloid staining in a transgenic mouse model of Alzheimer's disease (tgSwe).", "doi": "10.1021/acs.analchem.7b00313", "pmid": "28318232", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2020-01-23T16:35:14.859Z", "modified": "2021-06-21T15:39:50.308Z"}, {"entity": "publication", "iuid": "982044cf67514ddeb9751b625529811b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/982044cf67514ddeb9751b625529811b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/982044cf67514ddeb9751b625529811b"}}, "title": "Intranasal C3a treatment ameliorates cognitive impairment in a mouse model of neonatal hypoxic-ischemic brain injury.", "authors": [{"family": "Mor\u00e1n", "given": "Javier", "initials": "J"}, {"family": "Stokowska", "given": "Anna", "initials": "A", "orcid": "0000-0001-5237-3341", "researcher": {"href": "https://publications.scilifelab.se/researcher/ba5e258c6d934db08ed52a70cf6da7b9.json"}}, {"family": "Walker", "given": "Frederik R", "initials": "FR"}, {"family": "Mallard", "given": "Carina", "initials": "C", "orcid": "0000-0001-8953-919X", "researcher": {"href": "https://publications.scilifelab.se/researcher/2d0fa7de10554b5bb5a0e1ee64902aa1.json"}}, {"family": "Hagberg", "given": "Henrik", "initials": "H"}, {"family": "Pekna", "given": "Marcela", "initials": "M", "orcid": "0000-0003-2734-8237", "researcher": {"href": "https://publications.scilifelab.se/researcher/cf0f51a8f05b4e659ba192642603a7d6.json"}}], "type": "journal article", "published": "2017-04-00", "journal": {"title": "Exp. Neurol.", "issn": "1090-2430", "volume": "290", "issue": null, "pages": "74-84", "issn-l": "0014-4886"}, "abstract": "Perinatal asphyxia-induced brain injury is often associated with irreversible neurological complications such as intellectual disability and cerebral palsy but available therapies are limited. Novel neuroprotective therapies as well as approaches stimulating neural plasticity mechanism that can compensate for cell death after hypoxia-ischemia (HI) are urgently needed. We previously reported that single i.c.v. injection of complement-derived peptide C3a 1h after HI induction prevented HI-induced cognitive impairment when mice were tested as adults. Here, we tested the effects of intranasal treatment with C3a on HI-induced cognitive deficit. Using the object recognition test, we found that intranasal C3a treated mice were protected from HI-induced impairment of memory function assessed 6weeks after HI induction. C3a treatment ameliorated HI-induced reactive gliosis in the hippocampus, while it did not affect the extent of hippocampal tissue loss, neuronal cell density, expression of the pan-synaptic marker synapsin I or the expression of growth associated protein 43. In conclusion, our results reveal that brief pharmacological treatment with C3a using a clinically feasible non-invasive mode of administration ameliorates HI-induced cognitive impairment. Intranasal administration is a plausible route to deliver C3a into the brain of asphyxiated infants at high risk of developing hypoxic-ischemic encephalopathy.", "doi": "10.1016/j.expneurol.2017.01.001", "pmid": "28062175", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S0014-4886(17)30001-8"}], "notes": [], "created": "2020-01-23T16:35:48.152Z", "modified": "2021-06-21T15:40:51.853Z"}, {"entity": "publication", "iuid": "503a479740074fe8bfe99d3476e3be89", "links": {"self": {"href": "https://publications.scilifelab.se/publication/503a479740074fe8bfe99d3476e3be89.json"}, "display": {"href": "https://publications.scilifelab.se/publication/503a479740074fe8bfe99d3476e3be89"}}, "title": "Editorial for the special issue on \"Golgi-related human disorders\".", "authors": [{"family": "Micaroni", "given": "Massimo", "initials": "M"}], "type": "editorial", "published": "2017-04-00", "journal": {"title": "Tissue and Cell", "issn": "1532-3072", "volume": "49", "issue": "2 Pt A", "pages": "131-132", "issn-l": "0040-8166"}, "abstract": null, "doi": "10.1016/j.tice.2017.03.004", "pmid": "28342448", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S0040-8166(17)30084-8"}], "notes": [], "created": "2020-01-23T16:35:31.615Z", "modified": "2021-06-21T15:41:15.849Z"}, {"entity": "publication", "iuid": "837e52920ed54e07bb3af93391714b11", "links": {"self": {"href": "https://publications.scilifelab.se/publication/837e52920ed54e07bb3af93391714b11.json"}, "display": {"href": "https://publications.scilifelab.se/publication/837e52920ed54e07bb3af93391714b11"}}, "title": "An assessment of the importance of exposure routes to the uptake and internal localisation of fluorescent nanoparticles in zebrafish (Danio rerio), using light sheet microscopy.", "authors": [{"family": "Skjolding", "given": "L M", "initials": "LM"}, {"family": "A\u0161monait\u0117", "given": "G", "initials": "G"}, {"family": "J\u00f8lck", "given": "R I", "initials": "RI"}, {"family": "Andresen", "given": "T L", "initials": "TL"}, {"family": "Selck", "given": "H", "initials": "H"}, {"family": "Baun", "given": "A", "initials": "A"}, {"family": "Sturve", "given": "J", "initials": "J"}], "type": "journal article", "published": "2017-04-00", "journal": {"title": "Nanotoxicology", "issn": "1743-5404", "volume": "11", "issue": "3", "pages": "351-359", "issn-l": "1743-5390"}, "abstract": "A major challenge in nanoecotoxicology is finding suitable methods to determine the uptake and localisation of nanoparticles on a whole-organism level. Some uptake methods have been associated with artefacts induced by sample preparation, including staining for electron microscopy. This study used light sheet microscopy (LSM) to define the uptake and localisation of fluorescently labelled nanoparticles in living organisms with minimal sample preparation. Zebrafish (Danio rerio) were exposed to fluorescent gold nanoparticles (Au NPs) and fluorescent polystyrene NPs via aqueous or dietary exposure. The in vivo uptake and localisation of NPs were investigated using LSM at different time points (1, 3 and 7 days). A time-dependent increase in fluorescence was observed in the gut after dietary exposure to both Au NPs and polystyrene NPs. No fluorescence was observed within gut epithelia regardless of the NP exposure route indicating no or limited uptake via intestinal villi. Fish exposed to polystyrene NPs through the aqueous phase emitted fluorescence signals from the gills and intestine. Fluorescence was also detected in the head region of the fish after aqueous exposure to polystyrene NPs. This was not observed for Au NPs. Aqueous exposure to Au NPs resulted in increased relative swimming distance, while no effect was observed for other exposures. This study supports that the route of exposure is essential for the uptake and subsequent localisation of nanoparticles in zebrafish. Furthermore, it demonstrates that the localisation of NPs in whole living organisms can be visualised in real-time, using LSM.", "doi": "10.1080/17435390.2017.1306128", "pmid": "28286999", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2020-01-23T16:36:11.183Z", "modified": "2021-06-21T15:41:45.799Z"}, {"entity": "publication", "iuid": "ce4c21c5846e448796cea17aa113b78f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ce4c21c5846e448796cea17aa113b78f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ce4c21c5846e448796cea17aa113b78f"}}, "title": "Light-sensing via hydrogen peroxide and a peroxiredoxin.", "authors": [{"family": "Bodvard", "given": "Kristofer", "initials": "K"}, {"family": "Peeters", "given": "Ken", "initials": "K"}, {"family": "Roger", "given": "Friederike", "initials": "F"}, {"family": "Romanov", "given": "Natalie", "initials": "N"}, {"family": "Igbaria", "given": "Aeid", "initials": "A"}, {"family": "Welkenhuysen", "given": "Niek", "initials": "N"}, {"family": "Palais", "given": "Ga\u00ebl", "initials": "G"}, {"family": "Reiter", "given": "Wolfgang", "initials": "W"}, {"family": "Toledano", "given": "Michel B", "initials": "MB"}, {"family": "K\u00e4ll", "given": "Mikael", "initials": "M"}, {"family": "Molin", "given": "Mikael", "initials": "M", "orcid": "0000-0002-3903-8503", "researcher": {"href": "https://publications.scilifelab.se/researcher/12e9dc11d1b047d88913ea3bcb2694be.json"}}], "type": "journal article", "published": "2017-03-24", "journal": {"title": "Nat Commun", "issn": "2041-1723", "volume": "8", "issue": "1", "pages": "14791", "issn-l": "2041-1723"}, "abstract": "Yeast lacks dedicated photoreceptors; however, blue light still causes pronounced oscillations of the transcription factor Msn2 into and out of the nucleus. Here we show that this poorly understood phenomenon is initiated by a peroxisomal oxidase, which converts light into a hydrogen peroxide (H 2O2) signal that is sensed by the peroxiredoxin Tsa1 and transduced to thioredoxin, to counteract PKA-dependent Msn2 phosphorylation. Upon H2O2, the nuclear retention of PKA catalytic subunits, which contributes to delayed Msn2 nuclear concentration, is antagonized in a Tsa1-dependent manner. Conversely, peroxiredoxin hyperoxidation interrupts the H2O2 signal and drives Msn2 oscillations by superimposing on PKA feedback regulation. Our data identify a mechanism by which light could be sensed in all cells lacking dedicated photoreceptors. In particular, the use of H2O2 as a second messenger in signalling is common to Msn2 oscillations and to light-induced entrainment of circadian rhythms and suggests conserved roles for peroxiredoxins in endogenous rhythms.", "doi": "10.1038/ncomms14791", "pmid": "28337980", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "ncomms14791"}, {"db": "pmc", "key": "PMC5376668"}], "notes": [], "created": "2020-01-23T16:34:25.369Z", "modified": "2021-06-21T15:40:28.799Z"}, {"entity": "publication", "iuid": "1efc9e8a5f12496091a749b6a455d5b0", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1efc9e8a5f12496091a749b6a455d5b0.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1efc9e8a5f12496091a749b6a455d5b0"}}, "title": "Endocytic turnover of Rab8 controls cell polarization.", "authors": [{"family": "Vidal-Quadras", "given": "Maite", "initials": "M"}, {"family": "Holst", "given": "Mikkel R", "initials": "MR"}, {"family": "Francis", "given": "Monika K", "initials": "MK", "orcid": "0000-0002-6806-0515", "researcher": {"href": "https://publications.scilifelab.se/researcher/dbfa343ff09d4e7095fced73be91df51.json"}}, {"family": "Larsson", "given": "Elin", "initials": "E"}, {"family": "Hachimi", "given": "Mariam", "initials": "M"}, {"family": "Yau", "given": "Wai-Lok", "initials": "WL"}, {"family": "Per\u00e4nen", "given": "Johan", "initials": "J"}, {"family": "Mart\u00edn-Belmonte", "given": "Fernando", "initials": "F"}, {"family": "Lundmark", "given": "Richard", "initials": "R", "orcid": "0000-0001-9104-724X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3e1b756caa79468dab0f960e43cd61d3.json"}}], "type": "journal article", "published": "2017-03-15", "journal": {"title": "J. Cell. Sci.", "issn": "1477-9137", "volume": "130", "issue": "6", "pages": "1147-1157", "issn-l": "0021-9533"}, "abstract": "Adaptation of cell shape and polarization through the formation and retraction of cellular protrusions requires balancing of endocytosis and exocytosis combined with fine-tuning of the local activity of small GTPases like Rab8. Here, we show that endocytic turnover of the plasma membrane at protrusions is directly coupled to surface removal and inactivation of Rab8. Removal is induced by reduced membrane tension and mediated by the GTPase regulator associated with focal adhesion kinase-1 (GRAF1, also known as ARHGAP26), a regulator of clathrin-independent endocytosis. GRAF1-depleted cells were deficient in multi-directional spreading and displayed elevated levels of GTP-loaded Rab8, which was accumulated at the tips of static protrusions. Furthermore, GRAF1 depletion impaired lumen formation and spindle orientation in a 3D cell culture system, indicating that GRAF1 activity regulates polarity establishment. Our data suggest that GRAF1-mediated removal of Rab8 from the cell surface restricts its activity during protrusion formation, thereby facilitating dynamic adjustment of the polarity axis.", "doi": "10.1242/jcs.195420", "pmid": "28137756", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "jcs.195420"}, {"db": "pmc", "key": "PMC5358338"}], "notes": [], "created": "2020-01-23T16:36:50.803Z", "modified": "2021-06-21T15:44:32.527Z"}, {"entity": "publication", "iuid": "1f477773d0a9429885c8dab2a73981b1", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1f477773d0a9429885c8dab2a73981b1.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1f477773d0a9429885c8dab2a73981b1"}}, "title": "Peptide Functionalized Gold Nanoparticles as a Stimuli Responsive Contrast Medium in Multiphoton Microscopy.", "authors": [{"family": "Borglin", "given": "Johan", "initials": "J"}, {"family": "Seleg\u00e5rd", "given": "Robert", "initials": "R"}, {"family": "Aili", "given": "Daniel", "initials": "D", "orcid": "0000-0002-7001-9415", "researcher": {"href": "https://publications.scilifelab.se/researcher/cc760610215a4dee9061f28723b97e62.json"}}, {"family": "Ericson", "given": "Marica B", "initials": "MB", "orcid": "0000-0002-5987-5915", "researcher": {"href": "https://publications.scilifelab.se/researcher/af1f53e7cd234c36bdde7121e7204ed5.json"}}], "type": "journal article", "published": "2017-03-08", "journal": {"title": "Nano Lett.", "issn": "1530-6992", "volume": "17", "issue": "3", "pages": "2102-2108", "issn-l": "1530-6984"}, "abstract": "There is a need for biochemical contrast mediators with high signal-to-noise ratios enabling noninvasive biomedical sensing, for example, for neural sensing and protein-protein interactions, in addition to cancer diagnostics. The translational challenge is to develop a biocompatible approach ensuring high biochemical contrast while avoiding a raise of the background signal. We here present a concept where gold nanoparticles (AuNPs) can be utilized as a stimuli responsive contrast medium by chemically triggering their ability to exhibit multiphoton-induced luminescence (MIL) when performing multiphoton laser scanning microscopy (MPM). Proof-of-principle is demonstrated using peptide-functionalized AuNPs sensitive to zinc ions (Zn 2+). Dispersed particles are invisible in the MPM until addition of millimolar concentrations of Zn2+ upon which MIL is enabled through particle aggregation caused by specific peptide interactions and folding. The process can be reversed by removal of the Zn2+ using a chelator, thereby resuspending the AuNPs. In addition, the concept was demonstrated by exposing the particles to matrix metalloproteinase-7 (MMP-7) causing peptide digestion resulting in AuNP aggregation, significantly elevating the MIL signal from the background. The approach is based on the principle that aggregation shifts the plasmon resonance, elevating the absorption cross section in the near-infrared wavelength region enabling onset of MIL. This Letter demonstrates how biochemical sensing can be obtained in far-field MPM and should be further exploited as a future tool for noninvasive optical biosensing.", "doi": "10.1021/acs.nanolett.7b00611", "pmid": "28215085", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [], "notes": [], "created": "2020-01-23T16:34:34.853Z", "modified": "2021-06-21T15:41:57.977Z"}, {"entity": "publication", "iuid": "71cb03a7aa104761b89ada3693fad56c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/71cb03a7aa104761b89ada3693fad56c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/71cb03a7aa104761b89ada3693fad56c"}}, "title": "Postnatal development of the small intestinal mucosa drives age-dependent, regio-selective susceptibility to Escherichia coli K1 infection.", "authors": [{"family": "Birchenough", "given": "George M H", "initials": "GM"}, {"family": "Dalgakiran", "given": "Fatma", "initials": "F"}, {"family": "Witcomb", "given": "Luci A", "initials": "LA"}, {"family": "Johansson", "given": "Malin E V", "initials": "ME", "orcid": "0000-0002-4237-6677", "researcher": {"href": "https://publications.scilifelab.se/researcher/520dab35c19049c8b3f1083a92e60d56.json"}}, {"family": "McCarthy", "given": "Alex J", "initials": "AJ"}, {"family": "Hansson", "given": "Gunnar C", "initials": "GC", "orcid": "0000-0002-1900-1869", "researcher": {"href": "https://publications.scilifelab.se/researcher/44b3815603154322a6dac16f2fc1c1e9.json"}}, {"family": "Taylor", "given": "Peter W", "initials": "PW"}], "type": "journal article", "published": "2017-03-06", "journal": {"title": "Sci Rep", "issn": "2045-2322", "volume": "7", "issue": "1", "pages": "83", "issn-l": "2045-2322"}, "abstract": "The strong age dependency of neonatal systemic infection with Escherichia coli K1 can be replicated in the neonatal rat. Gastrointestinal (GI) colonization of two-day-old (P2) rats leads to invasion of the blood within 48 h of initiation of colonization; pups become progressively less susceptible to infection over the P2-P9 period. We show that, in animals colonized at P2 but not at P9, E. coli K1 bacteria gain access to the enterocyte surface in the mid-region of the small intestine and translocate through the epithelial cell monolayer by an intracellular pathway to the submucosa. In this region of the GI tract, the protective mucus barrier is poorly developed but matures to full thickness over P2-P9, coincident with the development of resistance to invasion. At P9, E. coli K1 bacteria are physically separated from villi by the mucus layer and their numbers controlled by mucus-embedded antimicrobial peptides, preventing invasion of host tissues.", "doi": "10.1038/s41598-017-00123-w", "pmid": "28250440", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "10.1038/s41598-017-00123-w"}, {"db": "pmc", "key": "PMC5427930"}], "notes": [], "created": "2020-01-23T16:34:09.203Z", "modified": "2021-06-21T14:59:19.303Z"}, {"entity": "publication", "iuid": "1e2f5f5b41994ebe87f808d019813e2c", "links": {"self": {"href": "https://publications.scilifelab.se/publication/1e2f5f5b41994ebe87f808d019813e2c.json"}, "display": {"href": "https://publications.scilifelab.se/publication/1e2f5f5b41994ebe87f808d019813e2c"}}, "title": "Delineating Amyloid Plaque Associated Neuronal Sphingolipids in Transgenic Alzheimer's Disease Mice (tgArcSwe) Using MALDI Imaging Mass Spectrometry.", "authors": [{"family": "Kaya", "given": "Ibrahim", "initials": "I"}, {"family": "Brinet", "given": "Dimitri", "initials": "D"}, {"family": "Michno", "given": "Wojciech", "initials": "W"}, {"family": "Syv\u00e4nen", "given": "Stina", "initials": "S"}, {"family": "Sehlin", "given": "Dag", "initials": "D"}, {"family": "Zetterberg", "given": "Henrik", "initials": "H"}, {"family": "Blennow", "given": "Kaj", "initials": "K"}, {"family": "Hanrieder", "given": "J\u00f6rg", "initials": "J", "orcid": "0000-0001-6059-198X", "researcher": {"href": "https://publications.scilifelab.se/researcher/4e65454100674f98bf8f2575093f2441.json"}}], "type": "journal article", "published": "2017-02-15", "journal": {"title": "ACS Chem Neurosci", "issn": "1948-7193", "volume": "8", "issue": "2", "pages": "347-355", "issn-l": "1948-7193"}, "abstract": "The major pathological hallmarks of Alzheimer's disease (AD) are the progressive aggregation and accumulation of beta-amyloid (A\u03b2) and hyperphosphorylated tau protein into neurotoxic deposits. A\u03b2 aggregation has been suggested as the critical early inducer, driving the disease progression. However, the factors that promote neurotoxic A\u03b2 aggregation remain elusive. Imaging mass spectrometry (IMS) is a powerful technique to comprehensively elucidate the spatial distribution patterns of lipids, peptides, and proteins in biological tissue sections. In the present study, matrix-assisted laser desorption/ionization (MALDI) mass spectrometry (MS)-based imaging was used on transgenic Alzheimer's disease mouse (tgArcSwe) brain tissue to investigate the sphingolipid microenvironment of individual A\u03b2 plaques and elucidate plaque-associated sphingolipid alterations. Multivariate data analysis was used to interrogate the IMS data for identifying pathologically relevant, anatomical features based on their lipid chemical profile. This approach revealed sphingolipid species that distinctly located to cortical and hippocampal deposits, whose A\u03b2 identity was further verified using fluorescent amyloid staining and immunohistochemistry. Subsequent multivariate statistical analysis of the spectral data revealed significant localization of gangliosides and ceramides species to A\u03b2 positive plaques, which was accompanied by distinct local reduction of sulfatides. These plaque-associated changes in sphingolipid levels implicate a functional role of sphingolipid metabolism in A\u03b2 plaque pathology and AD pathogenesis. Taken together, the presented data highlight the potential of imaging mass spectrometry as a powerful approach for probing A\u03b2 plaque-associated lipid changes underlying AD pathology.", "doi": "10.1021/acschemneuro.6b00391", "pmid": "27984697", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC5314428"}], "notes": [], "created": "2020-01-23T16:35:04.780Z", "modified": "2021-06-21T15:43:06.156Z"}, {"entity": "publication", "iuid": "b155d01aad66436bbb4048569af0b228", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b155d01aad66436bbb4048569af0b228.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b155d01aad66436bbb4048569af0b228"}}, "title": "MASTL is essential for anaphase entry of proliferating primordial germ cells and establishment of female germ cells in mice.", "authors": [{"family": "Risal", "given": "Sanjiv", "initials": "S"}, {"family": "Zhang", "given": "Jingjing", "initials": "J"}, {"family": "Adhikari", "given": "Deepak", "initials": "D"}, {"family": "Liu", "given": "Xiaoman", "initials": "X"}, {"family": "Shao", "given": "Jingchen", "initials": "J"}, {"family": "Hu", "given": "Mengwen", "initials": "M"}, {"family": "Busayavalasa", "given": "Kiran", "initials": "K"}, {"family": "Tu", "given": "Zhaowei", "initials": "Z"}, {"family": "Chen", "given": "Zijiang", "initials": "Z"}, {"family": "Kaldis", "given": "Philipp", "initials": "P", "orcid": "0000-0002-7247-7591", "researcher": {"href": "https://publications.scilifelab.se/researcher/e7faea8844574f828b494445e5f64bc4.json"}}, {"family": "Liu", "given": "Kui", "initials": "K"}], "type": "journal article", "published": "2017-02-07", "journal": {"title": "Cell Discov", "issn": "2056-5968", "volume": "3", "issue": "1", "pages": "16052", "issn-l": "2056-5968"}, "abstract": "In mammals, primordial germ cells (PGCs) are the embryonic cell population that serve as germ cell precursors in both females and males. During mouse embryonic development, the majority of PGCs are arrested at the G2 phase when they migrate into the hindgut at 7.75-8.75 dpc (days post coitum). It is after 9.5 dpc that the PGCs undergo proliferation with a doubling time of 12.6 h. The molecular mechanisms underlying PGC proliferation are however not well studied. In this work. Here we studied how MASTL (microtubule-associated serine/threonine kinase-like)/Greatwall kinase regulates the rapid proliferation of PGCs. We generated a mouse model where we specifically deleted Mastl in PGCs and found a significant loss of PGCs before the onset of meiosis in female PGCs. We further revealed that the deletion of Mastl in PGCs did not prevent mitotic entry, but led to a failure of the cells to proceed beyond metaphase-like stage, indicating that MASTL-mediated molecular events are indispensable for anaphase entry in PGCs. These mitotic defects further led to the death of Mastl-null PGCs by 12.5 dpc. Moreover, the defect in mitotic progression observed in the Mastl-null PGCs was rescued by simultaneous deletion of Ppp2r1a (\u03b1 subunit of PP2A). Thus, our results demonstrate that MASTL, PP2A, and therefore regulated phosphatase activity have a fundamental role in establishing female germ cell population in gonads by controlling PGC proliferation during embryogenesis.", "doi": "10.1038/celldisc.2016.52", "pmid": "28224044", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC5301161"}], "notes": [], "created": "2020-01-23T16:36:04.019Z", "modified": "2021-06-21T14:58:15.153Z"}, {"entity": "publication", "iuid": "b663df15bfdf4bfcacc56407fda3cb8a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/b663df15bfdf4bfcacc56407fda3cb8a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/b663df15bfdf4bfcacc56407fda3cb8a"}}, "title": "Complement peptide C3a stimulates neural plasticity after experimental brain ischaemia.", "authors": [{"family": "Stokowska", "given": "Anna", "initials": "A"}, {"family": "Atkins", "given": "Alison L", "initials": "AL"}, {"family": "Mor\u00e1n", "given": "Javier", "initials": "J"}, {"family": "Pekny", "given": "Tulen", "initials": "T"}, {"family": "Bulmer", "given": "Linda", "initials": "L"}, {"family": "Pascoe", "given": "Michaela C", "initials": "MC"}, {"family": "Barnum", "given": "Scott R", "initials": "SR"}, {"family": "Wetsel", "given": "Rick A", "initials": "RA"}, {"family": "Nilsson", "given": "Jonas A", "initials": "JA"}, {"family": "Dragunow", "given": "Mike", "initials": "M"}, {"family": "Pekna", "given": "Marcela", "initials": "M"}], "type": "journal article", "published": "2017-02-00", "journal": {"title": "Brain", "issn": "1460-2156", "volume": "140", "issue": "2", "pages": "353-369", "issn-l": "0006-8950"}, "abstract": "Ischaemic stroke induces endogenous repair processes that include proliferation and differentiation of neural stem cells and extensive rewiring of the remaining neural connections, yet about 50% of stroke survivors live with severe long-term disability. There is an unmet need for drug therapies to improve recovery by promoting brain plasticity in the subacute to chronic phase after ischaemic stroke. We previously showed that complement-derived peptide C3a regulates neural progenitor cell migration and differentiation in vitro and that C3a receptor signalling stimulates neurogenesis in unchallenged adult mice. To determine the role of C3a-C3a receptor signalling in ischaemia-induced neural plasticity, we subjected C3a receptor-deficient mice, GFAP-C3a transgenic mice expressing biologically active C3a in the central nervous system, and their respective wild-type controls to photothrombotic stroke. We found that C3a overexpression increased, whereas C3a receptor deficiency decreased post-stroke expression of GAP43 (P < 0.01), a marker of axonal sprouting and plasticity, in the peri-infarct cortex. To verify the translational potential of these findings, we used a pharmacological approach. Daily intranasal treatment of wild-type mice with C3a beginning 7 days after stroke induction robustly increased synaptic density (P < 0.01) and expression of GAP43 in peri-infarct cortex (P < 0.05). Importantly, the C3a treatment led to faster and more complete recovery of forepaw motor function (P < 0.05). We conclude that C3a-C3a receptor signalling stimulates post-ischaemic neural plasticity and intranasal treatment with C3a receptor agonists is an attractive approach to improve functional recovery after ischaemic brain injury.", "doi": "10.1093/brain/aww314", "pmid": "27956400", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "aww314"}], "notes": [], "created": "2020-01-23T16:36:17.901Z", "modified": "2021-06-21T15:43:36.124Z"}, {"entity": "publication", "iuid": "68d241823fb44e4d999225e98aff042d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/68d241823fb44e4d999225e98aff042d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/68d241823fb44e4d999225e98aff042d"}}, "title": "Copper chaperone Atox1 plays role in breast cancer cell migration.", "authors": [{"family": "Blockhuys", "given": "St\u00e9phanie", "initials": "S"}, {"family": "Wittung-Stafshede", "given": "Pernilla", "initials": "P", "orcid": "0000-0003-1058-1964", "researcher": {"href": "https://publications.scilifelab.se/researcher/9016aa00d62f439fb15532a1f4ba814e.json"}}], "type": "journal article", "published": "2017-01-29", "journal": {"title": "Biochem. Biophys. Res. Commun.", "issn": "1090-2104", "volume": "483", "issue": "1", "pages": "301-304", "issn-l": "0006-291X"}, "abstract": "Copper (Cu) is an essential transition metal ion required as cofactor in many key enzymes. After cell uptake of Cu, the metal is transported by the cytoplasmic Cu chaperone Atox1 to P 1B-type ATPases in the Golgi network for incorporation into Cu-dependent enzymes in the secretory path. Cu is vital for many steps of cancer progression and Atox1 was recently suggested to have additional functionality as a nuclear transcription factor. We here investigated the expression level, cellular localization and role in cell migration of Atox1 in an aggressive breast cancer cell line upon combining immunostaining, microscopy and a wound healing assay. We made the unexpected discovery that Atox1 accumulates at lamellipodia borders of migrating cancer cells and Atox1 silencing resulted in migration defects as evidenced from reduced wound closure. Therefore, we have discovered an unknown role of the Cu chaperone Atox1 in breast cancer cell migration.", "doi": "10.1016/j.bbrc.2016.12.148", "pmid": "28027931", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "S0006-291X(16)32208-2"}], "notes": [], "created": "2020-01-23T16:34:17.371Z", "modified": "2021-06-21T15:48:50.807Z"}, {"entity": "publication", "iuid": "3be6d8132ef84bd8a601931855600a3a", "links": {"self": {"href": "https://publications.scilifelab.se/publication/3be6d8132ef84bd8a601931855600a3a.json"}, "display": {"href": "https://publications.scilifelab.se/publication/3be6d8132ef84bd8a601931855600a3a"}}, "title": "Cell Cycle and Cell Size Dependent Gene Expression Reveals Distinct Subpopulations at Single-Cell Level.", "authors": [{"family": "Dolatabadi", "given": "Soheila", "initials": "S"}, {"family": "Candia", "given": "Juli\u00e1n", "initials": "J"}, {"family": "Akrap", "given": "Nina", "initials": "N"}, {"family": "Vannas", "given": "Christoffer", "initials": "C"}, {"family": "Tesan Tomic", "given": "Tajana", "initials": "T"}, {"family": "Losert", "given": "Wolfgang", "initials": "W"}, {"family": "Landberg", "given": "G\u00f6ran", "initials": "G"}, {"family": "\u00c5man", "given": "Pierre", "initials": "P"}, {"family": "St\u00e5hlberg", "given": "Anders", "initials": "A"}], "type": "journal article", "published": "2017-01-25", "journal": {"title": "Front Genet", "issn": "1664-8021", "volume": "8", "issue": null, "pages": "1", "issn-l": "1664-8021"}, "abstract": "Cell proliferation includes a series of events that is tightly regulated by several checkpoints and layers of control mechanisms. Most studies have been performed on large cell populations, but detailed understanding of cell dynamics and heterogeneity requires single-cell analysis. Here, we used quantitative real-time PCR, profiling the expression of 93 genes in single-cells from three different cell lines. Individual unsynchronized cells from three different cell lines were collected in different cell cycle phases (G0/G1 - S - G2/M) with variable cell sizes. We found that the total transcript level per cell and the expression of most individual genes correlated with progression through the cell cycle, but not with cell size. By applying the random forests algorithm, a supervised machine learning approach, we show how a multi-gene signature that classifies individual cells into their correct cell cycle phase and cell size can be generated. To identify the most predictive genes we used a variable selection strategy. Detailed analysis of cell cycle predictive genes allowed us to define subpopulations with distinct gene expression profiles and to calculate a cell cycle index that illustrates the transition of cells between cell cycle phases. In conclusion, we provide useful experimental approaches and bioinformatics to identify informative and predictive genes at the single-cell level, which opens up new means to describe and understand cell proliferation and subpopulation dynamics.", "doi": "10.3389/fgene.2017.00001", "pmid": "28179914", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC5263129"}], "notes": [], "created": "2020-01-23T16:34:51.889Z", "modified": "2021-06-21T15:44:54.553Z"}]}