{"entity": "journal", "iuid": "1cffb0b2137749a0b066f26b8c674193", "timestamp": "2026-03-12T19:04:41.756Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/EMBO%20Rep..json"}, "display": {"href": "https://publications.scilifelab.se/journal/EMBO%20Rep."}}, "title": "EMBO Rep.", "issn": "1469-3178", "issn-l": "1469-221X", "publications_count": 19, "publications": [{"entity": "publication", "iuid": "ceaf1969c97a4727bf39dfdf61d788be", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ceaf1969c97a4727bf39dfdf61d788be.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ceaf1969c97a4727bf39dfdf61d788be"}}, "title": "MIA40 suppresses cell death induced by apoptosis-inducing factor 1.", "authors": [{"family": "Mussulini", "given": "Ben Hur Marins", "initials": "BHM", "orcid": "0000-0003-4321-5709", "researcher": {"href": "https://publications.scilifelab.se/researcher/a5d73d54bba342edbc4af1606bf7af79.json"}}, {"family": "Maruszczak", "given": "Klaudia K", "initials": "KK", "orcid": "0000-0003-4080-9368", "researcher": {"href": "https://publications.scilifelab.se/researcher/456fceca130940b8a46137d5d2756043.json"}}, {"family": "Draczkowski", "given": "Piotr", "initials": "P", "orcid": "0000-0002-9408-2670", "researcher": {"href": "https://publications.scilifelab.se/researcher/efa7492df2464ccdb31320e4f5bb51e9.json"}}, {"family": "Borrero-Landazabal", "given": "Mayra A", "initials": "MA", "orcid": "0000-0003-3464-4042", "researcher": {"href": "https://publications.scilifelab.se/researcher/0a6bac5b1045422abddc2b136642cf4a.json"}}, {"family": "Ayyamperumal", "given": "Selvaraj", "initials": "S", "orcid": "0000-0003-2634-391X", "researcher": {"href": "https://publications.scilifelab.se/researcher/fe24ea5ef2494e60b633aea581c0bc89.json"}}, {"family": "Wnorowski", "given": "Artur", "initials": "A"}, {"family": "Wasilewski", "given": "Michal", "initials": "M", "orcid": "0000-0002-4890-5103", "researcher": {"href": "https://publications.scilifelab.se/researcher/772c69846aff4fd081a53a7f704eaff2.json"}}, {"family": "Chacinska", "given": "Agnieszka", "initials": "A", "orcid": "0000-0002-2832-2568", "researcher": {"href": "https://publications.scilifelab.se/researcher/0f6574d6e83b4e65a2721be9527de5ff.json"}}], "type": "journal article", "published": "2025-04-00", "journal": {"title": "EMBO Rep.", "issn": "1469-3178", "volume": "26", "issue": "7", "pages": "1835-1862", "issn-l": "1469-221X"}, "abstract": "Mitochondria harbor respiratory complexes that perform oxidative phosphorylation. Complex I is the first enzyme of the respiratory chain that oxidizes NADH. A dysfunction in complex I can result in higher cellular levels of NADH, which in turn strengthens the interaction between apoptosis-inducing factor 1 (AIFM1) and Mitochondrial intermembrane space import and assembly protein 40 (MIA40) in the mitochondrial intermembrane space. We investigated whether MIA40 modulates the activity of AIFM1 upon increased NADH/NAD+ balance. We found that in model cells characterized by an increase in NADH the AIFM1-MIA40 interaction is strengthened and these cells demonstrate resistance to AIFM1-induced cell death. Either silencing of MIA40, rescue of complex I, or depletion of NADH through the expression of yeast NADH-ubiquinone oxidoreductase-2 sensitized NDUFA13-KO cells to AIFM1-induced cell death. These findings indicate that the complex of MIA40 and AIFM1 suppresses AIFM1-induced cell death in a NADH-dependent manner. This study identifies an effector complex involved in regulating the programmed cell death that accommodates the metabolic changes in the cell and provides a molecular explanation for AIFM1-mediated chemoresistance of cancer cells.", "doi": "10.1038/s44319-025-00406-8", "pmid": "40055465", "labels": {"Cryo-EM": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC11976965"}, {"db": "pii", "key": "10.1038/s44319-025-00406-8"}], "notes": [], "created": "2025-11-25T08:59:24.731Z", "modified": "2025-11-25T08:59:25.528Z"}, {"entity": "publication", "iuid": "ca71d7f357f64f549fe916f1e8354fbb", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ca71d7f357f64f549fe916f1e8354fbb.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ca71d7f357f64f549fe916f1e8354fbb"}}, "title": "Structure of the MUC5AC VWD3 assembly responsible for the formation of net-like mucin polymers.", "authors": [{"family": "Trillo-Muyo", "given": "Sergio", "initials": "S", "orcid": "0000-0002-3135-9134", "researcher": {"href": "https://publications.scilifelab.se/researcher/2e6b6b830e9145a2ae3e6c10895acbee.json"}}, {"family": "Ermund", "given": "Anna", "initials": "A", "orcid": "0000-0002-3233-043X", "researcher": {"href": "https://publications.scilifelab.se/researcher/8215eeb434f84deaafa2f9f198bfb2bc.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": "2025-03-00", "journal": {"title": "EMBO Rep.", "issn": "1469-3178", "volume": "26", "issue": "6", "pages": "1457-1471", "issn-l": "1469-221X"}, "abstract": "Gel-forming mucins MUC5AC and MUC5B constitute the main structural component of the mucus in the respiratory system. Secreted mucins interact specifically with each other and other molecules giving mucus specific properties. We determined the cryoEM structures of the wild type D3 assembly of the human MUC5AC mucin and the structural single nucleotide polymorphisms (SNP) variants Arg996Gln and Arg1201Trp that affect intermolecular interactions. Our structures explain the MUC5AC N-terminal non-covalent oligomerization after secretion. The D3 assembly forms covalent dimers that can appear in two alternative conformations, open and closed, where the closed conformation dimers interact through an arginine-rich loop in the TIL3 domain to form tetramers. Our study provides a model to explain MUC5AC net-like structures and how the two SNPs will affect mucus organization, something that might affect lung and other diseases.", "doi": "10.1038/s44319-025-00395-8", "pmid": "40016425", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC11933400"}, {"db": "pii", "key": "10.1038/s44319-025-00395-8"}], "notes": [], "created": "2025-11-13T12:43:47.758Z", "modified": "2025-11-13T12:43:47.811Z"}, {"entity": "publication", "iuid": "aa5373351e6f42deb606d65eb1856c9f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/aa5373351e6f42deb606d65eb1856c9f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/aa5373351e6f42deb606d65eb1856c9f"}}, "title": "TGF\u03b2-induced long non-coding RNA LINC00313 activates Wnt signaling and promotes cholangiocarcinoma.", "authors": [{"family": "Papoutsoglou", "given": "Panagiotis", "initials": "P", "orcid": "0000-0003-2115-3500", "researcher": {"href": "https://publications.scilifelab.se/researcher/fb57fd2812074052937f7a71703f2d27.json"}}, {"family": "Pineau", "given": "Rapha\u00ebl", "initials": "R"}, {"family": "Leroux", "given": "Raffa\u00eble", "initials": "R"}, {"family": "Louis", "given": "Corentin", "initials": "C"}, {"family": "L'Haridon", "given": "Ana\u00efs", "initials": "A"}, {"family": "Foretek", "given": "Dominika", "initials": "D"}, {"family": "Morillon", "given": "Antonin", "initials": "A", "orcid": "0000-0002-0575-5264", "researcher": {"href": "https://publications.scilifelab.se/researcher/43a47c89d4894d5cb346858a214f6185.json"}}, {"family": "Banales", "given": "Jesus M", "initials": "JM", "orcid": "0000-0002-5224-2373", "researcher": {"href": "https://publications.scilifelab.se/researcher/72479d3cfc7a44d39a50be58d2654a0e.json"}}, {"family": "Gilot", "given": "David", "initials": "D", "orcid": "0000-0002-2646-671X", "researcher": {"href": "https://publications.scilifelab.se/researcher/227e4663903a4a08be6335745a0913f6.json"}}, {"family": "Aubry", "given": "Marc", "initials": "M", "orcid": "0000-0002-6954-8141", "researcher": {"href": "https://publications.scilifelab.se/researcher/2dca568239ea4837842457e1942cf3a2.json"}}, {"family": "Coulouarn", "given": "C\u00e9dric", "initials": "C", "orcid": "0000-0002-5692-9586", "researcher": {"href": "https://publications.scilifelab.se/researcher/9f02c657920f4e4e8898c890c699fa6b.json"}}], "type": "journal article", "published": "2024-03-00", "journal": {"title": "EMBO Rep.", "issn": "1469-3178", "volume": "25", "issue": "3", "pages": "1022-1054", "issn-l": "1469-221X"}, "abstract": "Cholangiocarcinoma is a devastating liver cancer characterized by high aggressiveness and therapy resistance, resulting in poor prognosis. Long non-coding RNAs and signals imposed by oncogenic pathways, such as transforming growth factor \u03b2 (TGF\u03b2), frequently contribute to cholangiocarcinogenesis. Here, we explore novel effectors of TGF\u03b2 signalling in cholangiocarcinoma. LINC00313 is identified as a novel TGF\u03b2 target gene. Gene expression and genome-wide chromatin accessibility profiling reveal that nuclear LINC00313 transcriptionally regulates genes involved in Wnt signalling, such as the transcriptional activator TCF7. LINC00313 gain-of-function enhances TCF/LEF-dependent transcription, promotes colony formation in vitro and accelerates tumour growth in vivo. Genes affected by LINC00313 over-expression in CCA tumours are associated with KRAS and TP53 mutations and reduce overall patient survival. Mechanistically, ACTL6A and BRG1, subunits of the SWI/SNF chromatin remodelling complex, interact with LINC00313 and affect TCF7 and SULF2 transcription. We propose a model whereby TGF\u03b2 induces LINC00313 in order to regulate the expression of hallmark Wnt pathway genes, in co-operation with SWI/SNF. By modulating key genes of the Wnt pathway, LINC00313 fine-tunes Wnt/TCF/LEF-dependent transcriptional responses and promotes cholangiocarcinogenesis.", "doi": "10.1038/s44319-024-00075-z", "pmid": "38332153", "labels": {"Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10933437"}, {"db": "pii", "key": "10.1038/s44319-024-00075-z"}], "notes": [], "created": "2024-11-27T13:00:18.632Z", "modified": "2024-11-27T13:00:19.302Z"}, {"entity": "publication", "iuid": "598feb16626f43cdb791a3f07b3a488b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/598feb16626f43cdb791a3f07b3a488b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/598feb16626f43cdb791a3f07b3a488b"}}, "title": "Molecular view of ER membrane remodeling by the Sec61/TRAP translocon.", "authors": [{"family": "Karki", "given": "Sudeep", "initials": "S", "orcid": "0000-0003-3851-1204", "researcher": {"href": "https://publications.scilifelab.se/researcher/2872667c8b6f400bb2373e19ef70e629.json"}}, {"family": "Javanainen", "given": "Matti", "initials": "M", "orcid": "0000-0003-4858-364X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9d89f643000047efb67c8b68340601b9.json"}}, {"family": "Rehan", "given": "Shahid", "initials": "S", "orcid": "0000-0003-1329-8056", "researcher": {"href": "https://publications.scilifelab.se/researcher/5fe8a426af3d4750906f849a48526806.json"}}, {"family": "Tranter", "given": "Dale", "initials": "D"}, {"family": "Kellosalo", "given": "Juho", "initials": "J"}, {"family": "Huiskonen", "given": "Juha", "initials": "J", "orcid": "0000-0002-0348-7323", "researcher": {"href": "https://publications.scilifelab.se/researcher/c858a2e60971462f9e53653320c9eb0f.json"}}, {"family": "Happonen", "given": "Lotta", "initials": "L", "orcid": "0000-0002-5922-4549", "researcher": {"href": "https://publications.scilifelab.se/researcher/a7af0a6faf6a48e7937a644be472edbe.json"}}, {"family": "Paavilainen", "given": "Ville", "initials": "V", "orcid": "0000-0002-3160-7767", "researcher": {"href": "https://publications.scilifelab.se/researcher/f76359e8b92b4b53af80c36d064a1a42.json"}}], "type": "journal article", "published": "2023-11-20", "journal": {"title": "EMBO Rep.", "issn": "1469-3178", "pages": "e57910", "issn-l": "1469-221X"}, "abstract": "Protein translocation across the endoplasmic reticulum (ER) membrane is an essential step during protein entry into the secretory pathway. The conserved Sec61 protein-conducting channel facilitates polypeptide translocation and coordinates cotranslational polypeptide-processing events. In cells, the majority of Sec61 is stably associated with a heterotetrameric membrane protein complex, the translocon-associated protein complex (TRAP), yet the mechanism by which TRAP assists in polypeptide translocation remains unknown. Here, we present the structure of the core Sec61/TRAP complex bound to a mammalian ribosome by cryogenic electron microscopy (cryo-EM). Ribosome interactions anchor the Sec61/TRAP complex in a conformation that renders the ER membrane locally thinner by significantly curving its lumenal leaflet. We propose that TRAP stabilizes the ribosome exit tunnel to assist nascent polypeptide insertion through Sec61 and provides a ratcheting mechanism into the ER lumen mediated by direct polypeptide interactions.", "doi": "10.15252/embr.202357910", "pmid": "37983950", "labels": {"Structural Proteomics": "Collaborative"}, "xrefs": [{"db": "PDB", "key": "8BF9"}], "notes": [], "created": "2023-12-01T13:22:27.535Z", "modified": "2023-12-01T13:22:27.636Z"}, {"entity": "publication", "iuid": "f70db074458d4aabb6293043f4663649", "links": {"self": {"href": "https://publications.scilifelab.se/publication/f70db074458d4aabb6293043f4663649.json"}, "display": {"href": "https://publications.scilifelab.se/publication/f70db074458d4aabb6293043f4663649"}}, "title": "Candida albicans induces neutrophil extracellular traps and leucotoxic hypercitrullination via candidalysin.", "authors": [{"family": "Unger", "given": "Lucas", "initials": "L", "orcid": "0000-0001-5719-7893", "researcher": {"href": "https://publications.scilifelab.se/researcher/9c3a9d7a9c5141e5ac137ea169b0379d.json"}}, {"family": "Skoluda", "given": "Samuel", "initials": "S", "orcid": "0009-0005-9443-1139", "researcher": {"href": "https://publications.scilifelab.se/researcher/f6728247ff024f4c8c33716e04fc9c6a.json"}}, {"family": "Backman", "given": "Emelie", "initials": "E", "orcid": "0000-0002-2482-1458", "researcher": {"href": "https://publications.scilifelab.se/researcher/e1c948f355df4a22a851a728f4d9d0f4.json"}}, {"family": "Amulic", "given": "Borko", "initials": "B", "orcid": "0000-0002-8518-8393", "researcher": {"href": "https://publications.scilifelab.se/researcher/eb328d8caec4405bb0962ef2c08dd2fe.json"}}, {"family": "Ponce-Garcia", "given": "Fernando M", "initials": "FM", "orcid": "0000-0003-0651-2704", "researcher": {"href": "https://publications.scilifelab.se/researcher/7a1f5935c505401bbb54b5a42818fa3f.json"}}, {"family": "Etiaba", "given": "Chinelo Nc", "initials": "CN"}, {"family": "Yellagunda", "given": "Sujan", "initials": "S"}, {"family": "Kr\u00fcger", "given": "Renate", "initials": "R"}, {"family": "von Bernuth", "given": "Horst", "initials": "H", "orcid": "0000-0002-5812-7675", "researcher": {"href": "https://publications.scilifelab.se/researcher/3794d0489f104a5faa633cfe1e45aac8.json"}}, {"family": "Bylund", "given": "Johan", "initials": "J", "orcid": "0000-0002-9094-6478", "researcher": {"href": "https://publications.scilifelab.se/researcher/782377f783314bcdb2d2c6d9be4532de.json"}}, {"family": "Hube", "given": "Bernhard", "initials": "B"}, {"family": "Naglik", "given": "Julian R", "initials": "JR", "orcid": "0000-0002-8072-7917", "researcher": {"href": "https://publications.scilifelab.se/researcher/835aedab7700450e858effbceec7d3c3.json"}}, {"family": "Urban", "given": "Constantin F", "initials": "CF", "orcid": "0000-0003-1438-1134", "researcher": {"href": "https://publications.scilifelab.se/researcher/3f963480368442a4b191c6db143936d9.json"}}], "type": "journal article", "published": "2023-11-06", "journal": {"title": "EMBO Rep.", "issn": "1469-3178", "volume": "24", "issue": "11", "pages": "e57571", "issn-l": "1469-221X"}, "abstract": "The peptide toxin candidalysin, secreted by Candida albicans hyphae, promotes stimulation of neutrophil extracellular traps (NETs). However, candidalysin alone triggers a distinct mechanism for NET-like structures (NLS), which are more compact and less fibrous than canonical NETs. Candidalysin activates NADPH oxidase and calcium influx, with both processes contributing to morphological changes in neutrophils resulting in NLS formation. NLS are induced by leucotoxic hypercitrullination, which is governed by calcium-induced protein arginine deaminase 4 activation and initiation of intracellular signalling events in a dose- and time-dependent manner. However, activation of signalling by candidalysin does not suffice to trigger downstream events essential for NET formation, as demonstrated by lack of lamin A/C phosphorylation, an event required for activation of cyclin-dependent kinases that are crucial for NET release. Candidalysin-triggered NLS demonstrate anti-Candida activity, which is resistant to nuclease treatment and dependent on the deprivation of Zn2+ . This study reveals that C. albicans hyphae releasing candidalysin concurrently trigger canonical NETs and NLS, which together form a fibrous sticky network that entangles C. albicans hyphae and efficiently inhibits their growth.", "doi": "10.15252/embr.202357571", "pmid": "37795769", "labels": {"Integrated Microscopy Technologies Ume\u00e5": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC10626426"}], "notes": [], "created": "2024-11-06T12:52:40.835Z", "modified": "2024-11-06T12:52:42.096Z"}, {"entity": "publication", "iuid": "795e2038e25f4e18a0ad1d522a57a3b3", "links": {"self": {"href": "https://publications.scilifelab.se/publication/795e2038e25f4e18a0ad1d522a57a3b3.json"}, "display": {"href": "https://publications.scilifelab.se/publication/795e2038e25f4e18a0ad1d522a57a3b3"}}, "title": "Reduced binding of apoE4 to complement factor H promotes amyloid-\u03b2 oligomerization and neuroinflammation.", "authors": [{"family": "Chernyaeva", "given": "Larisa", "initials": "L"}, {"family": "Ratti", "given": "Giorgio", "initials": "G", "orcid": "0000-0002-9938-2752", "researcher": {"href": "https://publications.scilifelab.se/researcher/fa9eca4386e3401690b213a563333708.json"}}, {"family": "Teiril\u00e4", "given": "Laura", "initials": "L"}, {"family": "Fudo", "given": "Satoshi", "initials": "S", "orcid": "0000-0001-9925-5131", "researcher": {"href": "https://publications.scilifelab.se/researcher/759009323fc946d4b76ca557460b14fe.json"}}, {"family": "Rankka", "given": "Uni", "initials": "U", "orcid": "0009-0006-0061-627X", "researcher": {"href": "https://publications.scilifelab.se/researcher/8876a5db4893489bb555826afc9b437e.json"}}, {"family": "Pelkonen", "given": "Anssi", "initials": "A"}, {"family": "Korhonen", "given": "Paula", "initials": "P", "orcid": "0000-0001-5856-1474", "researcher": {"href": "https://publications.scilifelab.se/researcher/3f477ee490c54644bb230db40930c331.json"}}, {"family": "Leskinen", "given": "Katarzyna", "initials": "K"}, {"family": "Keskitalo", "given": "Salla", "initials": "S", "orcid": "0000-0001-5555-1975", "researcher": {"href": "https://publications.scilifelab.se/researcher/6fcfe7acf8b34414af414dfe59619a78.json"}}, {"family": "Salokas", "given": "Kari", "initials": "K", "orcid": "0000-0002-4471-6698", "researcher": {"href": "https://publications.scilifelab.se/researcher/158142e4fff84a8e98e965eb73f574fa.json"}}, {"family": "Gkolfinopoulou", "given": "Christina", "initials": "C"}, {"family": "Crompton", "given": "Katrina E", "initials": "KE"}, {"family": "Javanainen", "given": "Matti", "initials": "M", "orcid": "0000-0003-4858-364X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9d89f643000047efb67c8b68340601b9.json"}}, {"family": "Happonen", "given": "Lotta", "initials": "L", "orcid": "0000-0002-5922-4549", "researcher": {"href": "https://publications.scilifelab.se/researcher/a7af0a6faf6a48e7937a644be472edbe.json"}}, {"family": "Varjosalo", "given": "Markku", "initials": "M", "orcid": "0000-0002-1340-9732", "researcher": {"href": "https://publications.scilifelab.se/researcher/631a0a4964d747399c0b1781e546f0ab.json"}}, {"family": "Malm", "given": "Tarja", "initials": "T"}, {"family": "Leinonen", "given": "Ville", "initials": "V", "orcid": "0000-0002-4282-4687", "researcher": {"href": "https://publications.scilifelab.se/researcher/0a0cda2550f84aa98a6492c9353900db.json"}}, {"family": "Chroni", "given": "Angeliki", "initials": "A", "orcid": "0000-0003-3107-1189", "researcher": {"href": "https://publications.scilifelab.se/researcher/c5fb9abe7c434935a7960d8d2ca06383.json"}}, {"family": "Saavalainen", "given": "P\u00e4ivi", "initials": "P"}, {"family": "Meri", "given": "Seppo", "initials": "S"}, {"family": "Kajander", "given": "Tommi", "initials": "T", "orcid": "0000-0002-5094-227X", "researcher": {"href": "https://publications.scilifelab.se/researcher/87663a9c5a1d4a3a8b8ecd9a7786da41.json"}}, {"family": "Wollman", "given": "Adam Jm", "initials": "AJ", "orcid": "0000-0002-5501-8131", "researcher": {"href": "https://publications.scilifelab.se/researcher/ab952da1fa7b4bf1943dca21d96ffd39.json"}}, {"family": "Nissil\u00e4", "given": "Eija", "initials": "E", "orcid": "0000-0002-8089-1266", "researcher": {"href": "https://publications.scilifelab.se/researcher/da4f5c3ecd1c4b39b1e7daa0b38741e7.json"}}, {"family": "Haapasalo", "given": "Karita", "initials": "K", "orcid": "0000-0002-9619-625X", "researcher": {"href": "https://publications.scilifelab.se/researcher/3b20237314dd44a18c5d66ce460570ee.json"}}], "type": "journal article", "published": "2023-05-08", "journal": {"title": "EMBO Rep.", "issn": "1469-3178", "pages": "e56467", "issn-l": "1469-221X"}, "abstract": "The APOE4 variant of apolipoprotein E (apoE) is the most prevalent genetic risk allele associated with late-onset Alzheimer's disease (AD). ApoE interacts with complement regulator factor H (FH), but the role of this interaction in AD pathogenesis is unknown. Here we elucidate the mechanism by which isoform-specific binding of apoE to FH alters A\u03b21-42-mediated neurotoxicity and clearance. Flow cytometry and transcriptomic analysis reveal that apoE and FH reduce binding of A\u03b21-42 to complement receptor 3 (CR3) and subsequent phagocytosis by microglia which alters expression of genes involved in AD. Moreover, FH forms complement-resistant oligomers with apoE/A\u03b21-42 complexes and the formation of these complexes is isoform specific with apoE2 and apoE3 showing higher affinity to FH than apoE4. These FH/apoE complexes reduce A\u03b21-42 oligomerization and toxicity, and colocalize with complement activator C1q deposited on A\u03b2 plaques in the brain. These findings provide an important mechanistic insight into AD pathogenesis and explain how the strongest genetic risk factor for AD predisposes for neuroinflammation in the early stages of the disease pathology.", "doi": "10.15252/embr.202256467", "pmid": "37155564", "labels": {"Structural Proteomics": "Collaborative"}, "xrefs": [{"db": "GEO", "key": "GSE193513"}], "notes": [], "created": "2023-05-31T19:05:44.032Z", "modified": "2023-05-31T19:05:44.613Z"}, {"entity": "publication", "iuid": "bb29de132a5745e4ad20d1359d784617", "links": {"self": {"href": "https://publications.scilifelab.se/publication/bb29de132a5745e4ad20d1359d784617.json"}, "display": {"href": "https://publications.scilifelab.se/publication/bb29de132a5745e4ad20d1359d784617"}}, "title": "Pyruvate metabolism guides definitive lineage specification during hematopoietic emergence.", "authors": [{"family": "Oburoglu", "given": "Leal", "initials": "L", "orcid": "0000-0003-0130-6602", "researcher": {"href": "https://publications.scilifelab.se/researcher/cac8186ea00246e6a07f421e492041e6.json"}}, {"family": "Mansell", "given": "Els", "initials": "E"}, {"family": "Canals", "given": "Isaac", "initials": "I", "orcid": "0000-0002-2689-268X", "researcher": {"href": "https://publications.scilifelab.se/researcher/0ee5182bf3ef430b989727fb28646ee9.json"}}, {"family": "Sigurdsson", "given": "Valgardur", "initials": "V"}, {"family": "Guibentif", "given": "Carolina", "initials": "C"}, {"family": "Soneji", "given": "Shamit", "initials": "S"}, {"family": "Woods", "given": "Niels-Bjarne", "initials": "NB", "orcid": "0000-0001-6052-922X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9c539424e21f41d1b006196a3b4b48bf.json"}}], "type": "journal article", "published": "2022-02-03", "journal": {"title": "EMBO Rep.", "issn": "1469-3178", "volume": "23", "issue": "2", "pages": "e54384", "issn-l": "1469-221X"}, "abstract": "During embryonic development, hematopoiesis occurs through primitive and definitive waves, giving rise to distinct blood lineages. Hematopoietic stem cells (HSCs) emerge from hemogenic endothelial (HE) cells, through endothelial-to-hematopoietic transition (EHT). In the adult, HSC quiescence, maintenance, and differentiation are closely linked to changes in metabolism. However, metabolic processes underlying the emergence of HSCs from HE cells remain unclear. Here, we show that the emergence of blood is regulated by multiple metabolic pathways that induce or modulate the differentiation toward specific hematopoietic lineages during human EHT. In both in vitro and in vivo settings, steering pyruvate use toward glycolysis or OXPHOS differentially skews the hematopoietic output of HE cells toward either an erythroid fate with primitive phenotype, or a definitive lymphoid fate, respectively. We demonstrate that glycolysis-mediated differentiation of HE toward primitive erythroid hematopoiesis is dependent on the epigenetic regulator LSD1. In contrast, OXPHOS-mediated differentiation of HE toward definitive hematopoiesis is dependent on cholesterol metabolism. Our findings reveal that during EHT, metabolism is a major regulator of primitive versus definitive hematopoietic differentiation.", "doi": "10.15252/embr.202154384", "pmid": "34914165", "labels": {"Clinical Genomics Lund": "Service", "Clinical Genomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8811648"}, {"db": "GEO", "key": "GSE141189"}], "notes": [], "created": "2023-02-23T13:55:05.551Z", "modified": "2023-02-23T13:55:05.727Z"}, {"entity": "publication", "iuid": "a8f05f12d3914490af074ff93cd54013", "links": {"self": {"href": "https://publications.scilifelab.se/publication/a8f05f12d3914490af074ff93cd54013.json"}, "display": {"href": "https://publications.scilifelab.se/publication/a8f05f12d3914490af074ff93cd54013"}}, "title": "Metabolic resistance to the inhibition of mitochondrial transcription revealed by CRISPR-Cas9 screen.", "authors": [{"family": "Mennuni", "given": "Mara", "initials": "M", "orcid": "0000-0001-6199-6233", "researcher": {"href": "https://publications.scilifelab.se/researcher/0d3b8d76aacd4f47ae62d0de66e9222a.json"}}, {"family": "Filograna", "given": "Roberta", "initials": "R", "orcid": "0000-0002-6581-9426", "researcher": {"href": "https://publications.scilifelab.se/researcher/7d215cffe2dc48a18d051a2229c8ce9f.json"}}, {"family": "Felser", "given": "Andrea", "initials": "A"}, {"family": "Bonekamp", "given": "Nina A", "initials": "NA", "orcid": "0000-0001-9748-8089", "researcher": {"href": "https://publications.scilifelab.se/researcher/786f4a3ca29a4033b3252e014e6785df.json"}}, {"family": "Giavalisco", "given": "Patrick", "initials": "P", "orcid": "0000-0002-4636-1827", "researcher": {"href": "https://publications.scilifelab.se/researcher/d8b3ada5024b4a23a32cdc392f92fb81.json"}}, {"family": "Lytovchenko", "given": "Oleksandr", "initials": "O", "orcid": "0000-0003-1032-2612", "researcher": {"href": "https://publications.scilifelab.se/researcher/3fb9454d524a470196c06792d4b47a7c.json"}}, {"family": "Larsson", "given": "Nils-G\u00f6ran", "initials": "N"}], "type": "journal article", "published": "2022-01-05", "journal": {"title": "EMBO Rep.", "issn": "1469-3178", "issn-l": "1469-221X", "volume": "23", "issue": "1", "pages": "e53054"}, "abstract": "Cancer cells depend on mitochondria to sustain their increased metabolic need and mitochondria therefore constitute possible targets for cancer treatment. We recently developed small-molecule inhibitors of mitochondrial transcription (IMTs) that selectively impair mitochondrial gene expression. IMTs have potent antitumor properties in vitro and in vivo, without affecting normal tissues. Because therapy-induced resistance is a major constraint to successful cancer therapy, we investigated mechanisms conferring resistance to IMTs. We employed a CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats)-(CRISP-associated protein 9) whole-genome screen to determine pathways conferring resistance to acute IMT1 treatment. Loss of genes belonging to von Hippel-Lindau (VHL) and mammalian target of rapamycin complex 1 (mTORC1) pathways caused resistance to acute IMT1 treatment and the relevance of these pathways was confirmed by chemical modulation. We also generated cells resistant to chronic IMT treatment to understand responses to persistent mitochondrial gene expression impairment. We report that IMT1-acquired resistance occurs through a compensatory increase of mitochondrial DNA (mtDNA) expression and cellular metabolites. We found that mitochondrial transcription factor A (TFAM) downregulation and inhibition of mitochondrial translation impaired survival of resistant cells. The identified susceptibility and resistance mechanisms to IMTs may be relevant for different types of mitochondria-targeted therapies.", "doi": "10.15252/embr.202153054", "pmid": "34779571", "labels": {"CRISPR Functional Genomics": "Service", "NGI Short read": "Service", "National Genomics Infrastructure": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8728608"}], "notes": [], "created": "2022-06-20T12:50:08.214Z", "modified": "2022-08-19T09:49:54.313Z"}, {"entity": "publication", "iuid": "66aa3609b1b14f69a46ab31a03c55b08", "links": {"self": {"href": "https://publications.scilifelab.se/publication/66aa3609b1b14f69a46ab31a03c55b08.json"}, "display": {"href": "https://publications.scilifelab.se/publication/66aa3609b1b14f69a46ab31a03c55b08"}}, "title": "CA10 regulates neurexin heparan sulfate addition via a direct binding in the secretory pathway.", "authors": [{"family": "Montoliu-Gaya", "given": "Laia", "initials": "L", "orcid": "0000-0001-7684-6318", "researcher": {"href": "https://publications.scilifelab.se/researcher/ddcfba9a14f14ba7ad912dcfd5fe92d9.json"}}, {"family": "Tietze", "given": "Daniel", "initials": "D", "orcid": "0000-0002-9251-1902", "researcher": {"href": "https://publications.scilifelab.se/researcher/c25c1c818e8a43039bdbbb7a376db42d.json"}}, {"family": "Kaminski", "given": "Debora", "initials": "D"}, {"family": "Mirgorodskaya", "given": "Ekaterina", "initials": "E"}, {"family": "Tietze", "given": "Alesia A", "initials": "AA"}, {"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": "2021-04-07", "journal": {"title": "EMBO Rep.", "issn": "1469-3178", "issn-l": "1469-221X", "volume": "22", "issue": "4", "pages": "e51349"}, "abstract": "Neurexins are presynaptic adhesion molecules that shape the molecular composition of synapses. Diversification of neurexins in numerous isoforms is believed to confer synapse-specific properties by engaging with distinct ligands. For example, a subset of neurexin molecules carry a heparan sulfate (HS) glycosaminoglycan that controls ligand binding, but how this post-translational modification is controlled is not known. Here, we observe that CA10, a ligand to neurexin in the secretory pathway, regulates neurexin-HS formation. CA10 is exclusively found on non-HS neurexin and CA10 expressed in neurons is sufficient to suppress HS addition and attenuate ligand binding and synapse formation induced by ligands known to recruit HS. This effect is mediated by a direct interaction in the secretory pathway that blocks the primary step of HS biosynthesis: xylosylation of the serine residue. NMR reveals that CA10 engages residues on either side of the serine that can be HS-modified, suggesting that CA10 sterically blocks xylosyltransferase access in Golgi. These results suggest a mechanism for the regulation of HS on neurexins and exemplify a new mechanism to regulate site-specific glycosylations.", "doi": "10.15252/embr.202051349", "pmid": "33586859", "labels": {"Glycoproteomics and MS Proteomics": "Collaborative", "Swedish NMR Centre": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC8024894"}, {"db": "Dryad", "key": "10.5061/dryad.z612jm69p"}], "notes": [], "created": "2021-07-02T14:04:56.568Z", "modified": "2025-10-17T13:03:56.066Z"}, {"entity": "publication", "iuid": "14f75a9338b14c19b1465b9d5f897d0b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/14f75a9338b14c19b1465b9d5f897d0b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/14f75a9338b14c19b1465b9d5f897d0b"}}, "title": "VEGF-B signaling impairs endothelial glucose transcytosis by decreasing membrane cholesterol content.", "authors": [{"family": "Moessinger", "given": "Christine", "initials": "C"}, {"family": "Nilsson", "given": "Ingrid", "initials": "I"}, {"family": "Muhl", "given": "Lars", "initials": "L"}, {"family": "Zeitelhofer", "given": "Manuel", "initials": "M"}, {"family": "Heller Sahlgren", "given": "Benjamin", "initials": "B"}, {"family": "Skogsberg", "given": "Josefin", "initials": "J"}, {"family": "Eriksson", "given": "Ulf", "initials": "U", "orcid": "0000-0002-4439-3980", "researcher": {"href": "https://publications.scilifelab.se/researcher/635596fee21941a6b444926375d19cd0.json"}}], "type": "journal article", "published": "2020-07-03", "journal": {"title": "EMBO Rep.", "issn": "1469-3178", "volume": "21", "issue": "7", "pages": "e49343", "issn-l": "1469-221X"}, "abstract": "Regulation of endothelial nutrient transport is poorly understood. Vascular endothelial growth factor B (VEGF-B) signaling in endothelial cells promotes uptake and transcytosis of fatty acids from the bloodstream to the underlying tissue, advancing pathological lipid accumulation and lipotoxicity in diabetic complications. Here, we demonstrate that VEGF-B limits endothelial glucose transport independent of fatty acid uptake. Specifically, VEGF-B signaling impairs recycling of low-density lipoprotein receptor (LDLR) to the plasma membrane, leading to reduced cholesterol uptake and membrane cholesterol loading. Reduced cholesterol levels in the membrane leads to a decrease in glucose transporter 1 (GLUT1)-dependent endothelial glucose uptake. Inhibiting VEGF-B in vivo reconstitutes membrane cholesterol levels and restores glucose uptake, which is of particular relevance for conditions involving insulin resistance and diabetic complications. In summary, our study reveals a mechanism whereby VEGF-B regulates endothelial nutrient uptake and highlights the impact of membrane cholesterol for regulation of endothelial glucose transport.", "doi": "10.15252/embr.201949343", "pmid": "32449307", "labels": {"Swedish Metabolomics Centre": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC7332976"}, {"db": "GEO", "key": "GSE146109"}], "notes": [], "created": "2020-12-11T12:04:53.020Z", "modified": "2025-10-17T13:03:16.721Z"}, {"entity": "publication", "iuid": "811125618a49401aba7f092bb01075dc", "links": {"self": {"href": "https://publications.scilifelab.se/publication/811125618a49401aba7f092bb01075dc.json"}, "display": {"href": "https://publications.scilifelab.se/publication/811125618a49401aba7f092bb01075dc"}}, "title": "Myc-dependent endothelial proliferation is controlled by phosphotyrosine 1212 in VEGF receptor-2.", "authors": [{"family": "Testini", "given": "Chiara", "initials": "C"}, {"family": "Smith", "given": "Ross O", "initials": "RO"}, {"family": "Jin", "given": "Yi", "initials": "Y"}, {"family": "Martinsson", "given": "Pernilla", "initials": "P"}, {"family": "Sun", "given": "Ying", "initials": "Y"}, {"family": "Hedlund", "given": "Marie", "initials": "M"}, {"family": "S\u00e1inz-Jaspeado", "given": "Miguel", "initials": "M"}, {"family": "Shibuya", "given": "Masabumi", "initials": "M"}, {"family": "Hellstr\u00f6m", "given": "Mats", "initials": "M"}, {"family": "Claesson-Welsh", "given": "Lena", "initials": "L", "orcid": "0000-0003-4275-2000", "researcher": {"href": "https://publications.scilifelab.se/researcher/647e2a349efd4e11827209883e86079b.json"}}], "type": "journal article", "published": "2019-11-05", "journal": {"volume": "20", "issn": "1469-3178", "issue": "11", "pages": "e47845", "title": "EMBO Rep.", "issn-l": "1469-221X"}, "abstract": "Exaggerated signaling by vascular endothelial growth factor (VEGF)-A and its receptor, VEGFR2, in pathologies results in poor vessel function. Still, pharmacological suppression of VEGFA/VEGFR2 may aggravate disease. Delineating VEGFR2 signaling in vivo provides strategies for suppression of specific VEGFR2-induced pathways. Three VEGFR2 tyrosine residues (Y949, Y1212, and Y1173) induce downstream signaling. Here, we show that knock-in of phenylalanine to create VEGFR2 Y1212F in C57Bl/6 and FVB mouse strains leads to loss of growth factor receptor-bound protein 2- and phosphoinositide 3'-kinase (PI3K)p85 signaling. C57Bl/6 Vegfr2 Y1212F/Y1212F show reduced embryonic endothelial cell (EC) proliferation and partial lethality. FVB Vegfr2Y1212F/Y1212F show reduced postnatal EC proliferation. Reduced EC proliferation in Vegfr2Y1212F/Y1212F explants is rescued by c-Myc overexpression. We conclude that VEGFR2 Y1212 signaling induces activation of extracellular-signal-regulated kinase (ERK)1/2 and Akt pathways required for c-Myc-dependent gene regulation, endothelial proliferation, and vessel stability.", "doi": "10.15252/embr.201947845", "pmid": "31545012", "labels": {"Global Proteomics and Proteogenomics": "Service"}, "xrefs": [{"db": "pmc", "key": "PMC6832004"}, {"db": "GEO", "key": "GSE136085"}], "notes": [], "created": "2020-01-07T12:30:14.040Z", "modified": "2021-06-16T16:20:25.433Z"}, {"entity": "publication", "iuid": "6fd62999f9b944feacd85cdc6d7564bf", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6fd62999f9b944feacd85cdc6d7564bf.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6fd62999f9b944feacd85cdc6d7564bf"}}, "title": "Post-metaphase correction of aberrant kinetochore-microtubule attachments in mammalian eggs.", "authors": [{"family": "Kouznetsova", "given": "Anna", "initials": "A", "orcid": "0000-0001-9059-4567", "researcher": {"href": "https://publications.scilifelab.se/researcher/05ada724837c497aaa6899997c67b2bc.json"}}, {"family": "Kitajima", "given": "Tomoya S", "initials": "TS"}, {"family": "Brismar", "given": "Hjalmar", "initials": "H", "orcid": "0000-0003-0578-4003", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ec23336e2ef4e298f340876f1136dce.json"}}, {"family": "H\u00f6\u00f6g", "given": "Christer", "initials": "C"}], "type": "journal article", "published": "2019-08-00", "journal": {"volume": "20", "issn": "1469-3178", "issue": "8", "pages": "e47905", "title": "EMBO Rep.", "issn-l": "1469-221X"}, "abstract": "The accuracy of the two sequential meiotic divisions in oocytes is essential for creating a haploid gamete with a normal chromosomal content. Here, we have analysed the 3D dynamics of chromosomes during the second meiotic division in live mouse oocytes. We find that chromosomes form stable kinetochore-microtubule attachments at the end of prometaphase II stage that are retained until anaphase II onset. Remarkably, we observe that more than 20% of the kinetochore-microtubule attachments at the metaphase II stage are merotelic or lateral. However, < 1% of all chromosomes at onset of anaphase II are found to lag at the spindle equator and < 10% of the laggards missegregate and give rise to aneuploid gametes. Our results demonstrate that aberrant kinetochore-microtubule attachments are not corrected at the metaphase stage of the second meiotic division. Thus, the accuracy of the chromosome segregation process in mouse oocytes during meiosis II is ensured by an efficient correction process acting at the anaphase stage.", "doi": "10.15252/embr.201947905", "pmid": "31290587", "labels": {"Integrated Microscopy Technologies Stockholm": "Collaborative"}, "xrefs": [{"db": "pmc", "key": "PMC6680117"}], "notes": [], "created": "2019-08-07T10:31:27.396Z", "modified": "2021-07-05T13:39:45.022Z"}, {"entity": "publication", "iuid": "6d92a7ca3d7f443f872186db5e57d704", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6d92a7ca3d7f443f872186db5e57d704.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6d92a7ca3d7f443f872186db5e57d704"}}, "title": "FET family fusion oncoproteins target the SWI/SNF chromatin remodeling complex.", "authors": [{"family": "Lind\u00e9n", "given": "Malin", "initials": "M"}, {"family": "Thomsen", "given": "Christer", "initials": "C"}, {"family": "Grundevik", "given": "Pernilla", "initials": "P"}, {"family": "Jonasson", "given": "Emma", "initials": "E"}, {"family": "Andersson", "given": "Daniel", "initials": "D"}, {"family": "Runnberg", "given": "Rikard", "initials": "R"}, {"family": "Dolatabadi", "given": "Soheila", "initials": "S"}, {"family": "Vannas", "given": "Christoffer", "initials": "C"}, {"family": "Luna Santamar\u03afa", "given": "Manuel", "initials": "M"}, {"family": "Fagman", "given": "Henrik", "initials": "H"}, {"family": "St\u00e5hlberg", "given": "Anders", "initials": "A"}, {"family": "\u00c5man", "given": "Pierre", "initials": "P"}], "type": "journal article", "published": "2019-05-00", "journal": {"title": "EMBO Rep.", "issn": "1469-3178", "volume": "20", "issue": "5", "issn-l": "1469-221X"}, "abstract": "Members of the human FET family of RNA-binding proteins, comprising FUS, EWSR1, and TAF15, are ubiquitously expressed and engage at several levels of gene regulation. Many sarcomas and leukemias are characterized by the expression of fusion oncogenes with FET genes as 5' partners and alternative transcription factor-coding genes as 3' partners. Here, we report that the N terminus of normal FET proteins and their oncogenic fusion counterparts interact with the SWI/SNF chromatin remodeling complex. In contrast to normal FET proteins, increased fractions of FET oncoproteins bind SWI/SNF, indicating a deregulated and enhanced interaction in cancer. Forced expression of FET oncogenes caused changes of global H3K27 trimethylation levels, accompanied by altered gene expression patterns suggesting a shift in the antagonistic balance between SWI/SNF and repressive polycomb group complexes. Thus, deregulation of SWI/SNF activity could provide a unifying pathogenic mechanism for the large group of tumors caused by FET fusion oncoproteins. These results may help to develop common strategies for therapy.", "doi": "10.15252/embr.201845766", "pmid": "30962207", "labels": {"Glycoproteomics and MS Proteomics": "Service"}, "xrefs": [{"db": "pii", "key": "embr.201845766"}, {"db": "pmc", "key": "PMC6500973"}], "notes": [], "created": "2020-01-30T15:58:44.885Z", "modified": "2024-01-16T13:46:31.833Z"}, {"entity": "publication", "iuid": "ac65bcde708c467a89a3c3d866344ce9", "links": {"self": {"href": "https://publications.scilifelab.se/publication/ac65bcde708c467a89a3c3d866344ce9.json"}, "display": {"href": "https://publications.scilifelab.se/publication/ac65bcde708c467a89a3c3d866344ce9"}}, "title": "Sequentially acting SOX proteins orchestrate astrocyte\u2010 and oligodendrocyte\u2010specific gene expression", "authors": [{"family": "Klum", "given": "Susanne", "initials": "S"}, {"family": "Zaouter", "given": "C\u00e9cile", "initials": "C"}, {"family": "Alekseenko", "given": "Zhanna", "initials": "Z"}, {"family": "Bj\u00f6rklund", "given": "\u00c5sa K", "initials": "\u00c5K"}, {"family": "Hagey", "given": "Daniel W", "initials": "DW"}, {"family": "Ericson", "given": "Johan", "initials": "J"}, {"family": "Muhr", "given": "Jonas", "initials": "J"}, {"family": "Bergsland", "given": "Maria", "initials": "M"}], "type": "journal-article", "published": "2018-08-30", "journal": {"volume": null, "issn": "1469-3178", "issue": null, "pages": "e46635", "title": "EMBO Rep.", "issn-l": "1469-221X"}, "abstract": "SOX transcription factors have important roles during astrocyte and oligodendrocyte development, but how glial genes are specified and activated in a sub-lineage-specific fashion remains unknown. Here, we define glial-specific gene expression in the developing spinal cord using single-cell RNA-sequencing. Moreover, by ChIP-seq analyses we show that these glial gene sets are extensively preselected already in multipotent neural precursor cells through prebinding by SOX3. In the subsequent lineage-restricted glial precursor cells, astrocyte genes become additionally targeted by SOX9 at DNA regions strongly enriched for Nfi binding motifs. Oligodendrocyte genes instead are prebound by SOX9 only, at sites which during oligodendrocyte maturation are targeted by SOX10. Interestingly, reporter gene assays and functional studies in the spinal cord reveal that SOX3 binding represses the synergistic activation of astrocyte genes by SOX9 and NFIA, whereas oligodendrocyte genes are activated in a combinatorial manner by SOX9 and SOX10. These genome-wide studies demonstrate how sequentially expressed SOX proteins act on lineage-specific regulatory DNA elements to coordinate glial gene expression both in a temporal and in a sub-lineage-specific fashion.", "doi": "10.15252/embr.201846635", "pmid": "30166336", "labels": {"National Genomics Infrastructure": "Service", "NGI Uppsala (SNP&SEQ Technology Platform)": "Service", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics Long-term Support WABI": "Collaborative", "Bioinformatics Support for Computational Resources": "Service", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [], "notes": [], "created": "2018-09-28T16:05:21.577Z", "modified": "2024-01-16T13:48:45.697Z"}, {"entity": "publication", "iuid": "9203b36c328341a68a31f5b7742b332b", "links": {"self": {"href": "https://publications.scilifelab.se/publication/9203b36c328341a68a31f5b7742b332b.json"}, "display": {"href": "https://publications.scilifelab.se/publication/9203b36c328341a68a31f5b7742b332b"}}, "title": "The structure of the tetanus toxin reveals pH-mediated domain dynamics.", "authors": [{"family": "Masuyer", "given": "Geoffrey", "initials": "G", "orcid": "0000-0002-9527-2310", "researcher": {"href": "https://publications.scilifelab.se/researcher/41dcc0806dba4a56bb04725812f3a000.json"}}, {"family": "Conrad", "given": "Julian", "initials": "J", "orcid": "0000-0003-2475-0431", "researcher": {"href": "https://publications.scilifelab.se/researcher/a3eff719b8fa41a9a1e1e3876c0b66d2.json"}}, {"family": "Stenmark", "given": "P\u00e5l", "initials": "P", "orcid": "0000-0003-4777-3417", "researcher": {"href": "https://publications.scilifelab.se/researcher/d97eba9f5edf4d76a5259c4baa8366c5.json"}}], "type": "journal article", "published": "2017-08-00", "journal": {"volume": "18", "issn": "1469-3178", "issue": "8", "pages": "1306-1317", "title": "EMBO Rep.", "issn-l": "1469-221X"}, "abstract": "The tetanus neurotoxin (TeNT) is a highly potent toxin produced by Clostridium tetani that inhibits neurotransmission of inhibitory interneurons, causing spastic paralysis in the tetanus disease. TeNT differs from the other clostridial neurotoxins by its unique ability to target the central nervous system by retrograde axonal transport. The crystal structure of the tetanus toxin reveals a \"closed\" domain arrangement stabilised by two disulphide bridges, and the molecular details of the toxin's interaction with its polysaccharide receptor. An integrative analysis combining X-ray crystallography, solution scattering and single particle electron cryo-microscopy reveals pH-mediated domain rearrangements that may give TeNT the ability to adapt to the multiple environments encountered during intoxication, and facilitate binding to distinct receptors.", "doi": "10.15252/embr.201744198", "pmid": "28645943", "labels": {"Cryo-EM": "Service"}, "xrefs": [{"db": "pii", "key": "embr.201744198"}, {"db": "pmc", "key": "PMC5538627"}], "notes": [], "created": "2017-10-16T16:21:49.646Z", "modified": "2021-06-21T15:33:47.706Z"}, {"entity": "publication", "iuid": "62f169b406de4521be7b9140b9a119a2", "links": {"self": {"href": "https://publications.scilifelab.se/publication/62f169b406de4521be7b9140b9a119a2.json"}, "display": {"href": "https://publications.scilifelab.se/publication/62f169b406de4521be7b9140b9a119a2"}}, "title": "High density of REC8 constrains sister chromatid axes and prevents illegitimate synaptonemal complex formation.", "authors": [{"family": "Agostinho", "given": "Ana", "initials": "A"}, {"family": "Manneberg", "given": "Otto", "initials": "O"}, {"family": "van Schendel", "given": "Robin", "initials": "R"}, {"family": "Hern\u00e1ndez-Hern\u00e1ndez", "given": "Abrahan", "initials": "A"}, {"family": "Kouznetsova", "given": "Anna", "initials": "A"}, {"family": "Blom", "given": "Hans", "initials": "H", "orcid": "0000-0002-5584-9170", "researcher": {"href": "https://publications.scilifelab.se/researcher/3ce356a74dc84e0ea6af85397f11d869.json"}}, {"family": "Brismar", "given": "Hjalmar", "initials": "H", "orcid": "0000-0003-0578-4003", "researcher": {"href": "https://publications.scilifelab.se/researcher/1ec23336e2ef4e298f340876f1136dce.json"}}, {"family": "H\u00f6\u00f6g", "given": "Christer", "initials": "C"}], "type": "journal article", "published": "2016-06-00", "journal": {"volume": "17", "issn": "1469-3178", "issue": "6", "pages": "901-913", "title": "EMBO Rep.", "issn-l": "1469-221X"}, "abstract": "During meiosis, cohesin complexes mediate sister chromatid cohesion (SCC), synaptonemal complex (SC) assembly and synapsis. Here, using super-resolution microscopy, we imaged sister chromatid axes in mouse meiocytes that have normal or reduced levels of cohesin complexes, assessing the relationship between localization of cohesin complexes, SCC and SC formation. We show that REC8 foci are separated from each other by a distance smaller than 15% of the total chromosome axis length in wild-type meiocytes. Reduced levels of cohesin complexes result in a local separation of sister chromatid axial elements (LSAEs), as well as illegitimate SC formation at these sites. REC8 but not RAD21 or RAD21L cohesin complexes flank sites of LSAEs, whereas RAD21 and RAD21L appear predominantly along the separated sister-chromatid axes. Based on these observations and a quantitative distribution analysis of REC8 along sister chromatid axes, we propose that the high density of randomly distributed REC8 cohesin complexes promotes SCC and prevents illegitimate SC formation.", "doi": "10.15252/embr.201642030", "pmid": "27170622", "labels": {"Integrated Microscopy Technologies Stockholm": "Collaborative"}, "xrefs": [{"db": "pii", "key": "embr.201642030"}, {"db": "pmc", "key": "PMC5278604"}], "notes": [], "created": "2017-05-03T12:59:25.552Z", "modified": "2021-07-05T13:48:51.549Z"}, {"entity": "publication", "iuid": "0997fff6de91435e9c43a1b1be58382d", "links": {"self": {"href": "https://publications.scilifelab.se/publication/0997fff6de91435e9c43a1b1be58382d.json"}, "display": {"href": "https://publications.scilifelab.se/publication/0997fff6de91435e9c43a1b1be58382d"}}, "title": "Regulating retrotransposon activity through the use of alternative transcription start sites.", "authors": [{"family": "Persson", "given": "Jenna", "initials": "J"}, {"family": "Steglich", "given": "Babett", "initials": "B"}, {"family": "Smialowska", "given": "Agata", "initials": "A"}, {"family": "Boyd", "given": "Mette", "initials": "M"}, {"family": "Bornholdt", "given": "Jette", "initials": "J"}, {"family": "Andersson", "given": "Robin", "initials": "R"}, {"family": "Schurra", "given": "Catherine", "initials": "C"}, {"family": "Arcangioli", "given": "Benoit", "initials": "B"}, {"family": "Sandelin", "given": "Albin", "initials": "A"}, {"family": "Nielsen", "given": "Olaf", "initials": "O"}, {"family": "Ekwall", "given": "Karl", "initials": "K"}], "type": "journal article", "published": "2016-05-00", "journal": {"volume": "17", "issn": "1469-3178", "issue": "5", "pages": "753-768", "title": "EMBO Rep.", "issn-l": "1469-221X"}, "abstract": "Retrotransposons, the ancestors of retroviruses, have the potential for gene disruption and genomic takeover if not kept in check. Paradoxically, although host cells repress these elements by multiple mechanisms, they are transcribed and are even activated under stress conditions. Here, we describe a new mechanism of retrotransposon regulation through transcription start site (TSS) selection by altered nucleosome occupancy. We show that Fun30 chromatin remodelers cooperate to maintain a high level of nucleosome occupancy at retrotransposon-flanking long terminal repeat (LTR) elements. This enforces the use of a downstream TSS and the production of a truncated RNA incapable of reverse transcription and retrotransposition. However, in stressed cells, nucleosome occupancy at LTR elements is reduced, and the TSS shifts to allow for productive transcription. We propose that controlled retrotransposon transcription from a nonproductive TSS allows for rapid stress-induced activation, while preventing uncontrolled transposon activity in the genome.", "doi": "10.15252/embr.201541866", "pmid": "26902262", "labels": {"Bioinformatics and Expression Analysis (BEA)": "Service", "Bioinformatics Support and Infrastructure": "Collaborative", "Bioinformatics Support, Infrastructure and Training": "Collaborative", "Bioinformatics (NBIS)": "Collaborative"}, "xrefs": [{"db": "pii", "key": "embr.201541866"}, {"db": "pmc", "key": "PMC5341516"}], "notes": [], "created": "2017-05-03T13:00:50.428Z", "modified": "2020-01-21T13:53:21.212Z"}, {"entity": "publication", "iuid": "fe207fc9ff3a4b668a2838994dd20492", "links": {"self": {"href": "https://publications.scilifelab.se/publication/fe207fc9ff3a4b668a2838994dd20492.json"}, "display": {"href": "https://publications.scilifelab.se/publication/fe207fc9ff3a4b668a2838994dd20492"}}, "title": "The composition of the gut microbiota shapes the colon mucus barrier.", "authors": [{"family": "Jakobsson", "given": "Hedvig E", "initials": "HE"}, {"family": "Rodr\u00edguez-Pi\u00f1eiro", "given": "Ana M", "initials": "AM"}, {"family": "Sch\u00fctte", "given": "Andr\u00e9", "initials": "A"}, {"family": "Ermund", "given": "Anna", "initials": "A"}, {"family": "Boysen", "given": "Preben", "initials": "P"}, {"family": "Bemark", "given": "Mats", "initials": "M"}, {"family": "Sommer", "given": "Felix", "initials": "F"}, {"family": "B\u00e4ckhed", "given": "Fredrik", "initials": "F"}, {"family": "Hansson", "given": "Gunnar C", "initials": "GC"}, {"family": "Johansson", "given": "Malin E V", "initials": "ME"}], "type": "journal article", "published": "2015-02-00", "journal": {"volume": "16", "issn": "1469-3178", "issue": "2", "pages": "164-177", "title": "EMBO Rep.", "issn-l": "1469-221X"}, "abstract": "Two C57BL/6 mice colonies maintained in two rooms of the same specific pathogen-free (SPF) facility were found to have different gut microbiota and a mucus phenotype that was specific for each colony. The thickness and growth of the colon mucus were similar in the two colonies. However, one colony had mucus that was impenetrable to bacteria or beads the size of bacteria-which is comparable to what we observed in free-living wild mice-whereas the other colony had an inner mucus layer penetrable to bacteria and beads. The different properties of the mucus depended on the microbiota, as they were transmissible by transfer of caecal microbiota to germ-free mice. Mice with an impenetrable mucus layer had increased amounts of Erysipelotrichi, whereas mice with a penetrable mucus layer had higher levels of Proteobacteria and TM7 bacteria in the distal colon mucus. Thus, our study shows that bacteria and their community structure affect mucus barrier properties in ways that can have implications for health and disease. It also highlights that genetically identical animals housed in the same facility can have rather distinct microbiotas and barrier structures.", "doi": "10.15252/embr.201439263", "pmid": "25525071", "labels": {"National Genomics Infrastructure": null, "NGI Stockholm (Genomics Applications)": null, "NGI Stockholm (Genomics Production)": null}, "xrefs": [{"db": "pii", "key": "embr.201439263"}, {"db": "pmc", "key": "PMC4328744"}], "notes": [], "created": "2017-05-02T12:57:25.565Z", "modified": "2020-01-21T13:56:06.529Z"}, {"entity": "publication", "iuid": "14e9532cc5b04ab5b73ec0e0ef75acff", "links": {"self": {"href": "https://publications.scilifelab.se/publication/14e9532cc5b04ab5b73ec0e0ef75acff.json"}, "display": {"href": "https://publications.scilifelab.se/publication/14e9532cc5b04ab5b73ec0e0ef75acff"}}, "title": "Structural insights into substrate recognition in proton-dependent oligopeptide transporters.", "authors": [{"family": "Guettou", "given": "Fatma", "initials": "F"}, {"family": "Quistgaard", "given": "Esben M", "initials": "EM"}, {"family": "Tr\u00e9saugues", "given": "Lionel", "initials": "L"}, {"family": "Moberg", "given": "Per", "initials": "P"}, {"family": "Jegersch\u00f6ld", "given": "Caroline", "initials": "C"}, {"family": "Zhu", "given": "Lin", "initials": "L"}, {"family": "Jong", "given": "Agnes Jin Oi", "initials": "AJ"}, {"family": "Nordlund", "given": "P\u00e4r", "initials": "P"}, {"family": "L\u00f6w", "given": "Christian", "initials": "C"}], "type": "journal article", "published": "2013-09-00", "journal": {"volume": "14", "issn": "1469-3178", "issue": "9", "pages": "804-810", "title": "EMBO Rep.", "issn-l": "1469-221X"}, "abstract": "Short-chain peptides are transported across membranes through promiscuous proton-dependent oligopeptide transporters (POTs)--a subfamily of the major facilitator superfamily (MFS). The human POTs, PEPT1 and PEPT2, are also involved in the absorption of various drugs in the gut as well as transport to target cells. Here, we present a structure of an oligomeric POT transporter from Shewanella oneidensis (PepTSo2), which was crystallized in the inward open conformation in complex with the peptidomimetic alafosfalin. All ligand-binding residues are highly conserved and the structural insights presented here are therefore likely to also apply to human POTs.", "doi": "10.1038/embor.2013.107", "pmid": "23867627", "labels": {"Protein Science Facility (PSF)": null}, "xrefs": [{"db": "pii", "key": "embor2013107"}, {"db": "pmc", "key": "PMC3790050"}, {"db": "PDB", "key": "4LEP"}], "notes": [], "created": "2017-05-04T15:03:47.294Z", "modified": "2017-09-06T11:42:08.981Z"}], "created": "2017-05-09T09:12:41.313Z", "modified": "2020-11-27T13:14:03.242Z"}