[{"doi":"10.1016/j.jtbi.2021.110729","year":"2021","day":"24","pmid":1,"external_id":{"pmid":["33901507"],"isi":["000659161500002"]},"date_updated":"2026-07-06T12:58:31Z","date_published":"2021-04-24T00:00:00Z","isi":1,"main_file_link":[{"open_access":"1","url":"https://www.biorxiv.org/content/10.1101/477489v1"}],"language":[{"iso":"eng"}],"acknowledgement":"This work was supported by the Russian Science Foundation grant N 16-14-10173.","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","keyword":["General Biochemistry","Genetics and Molecular Biology","Modelling and Simulation","Statistics and Probability","General Immunology and Microbiology","Applied Mathematics","General Agricultural and Biological Sciences","General Medicine"],"scopus_import":"1","type":"journal_article","oa_version":"Preprint","_id":"9387","department":[{"_id":"GradSch"}],"intvolume":"       524","das_tickbox":"1","citation":{"ieee":"K. Khudiakova, T. Y. Neretina, and A. S. Kondrashov, “Two linked loci under mutation-selection balance and Muller’s ratchet,” <i>Journal of Theoretical Biology</i>, vol. 524. Elsevier, 2021.","apa":"Khudiakova, K., Neretina, T. Y., &#38; Kondrashov, A. S. (2021). Two linked loci under mutation-selection balance and Muller’s ratchet. <i>Journal of Theoretical Biology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.jtbi.2021.110729\">https://doi.org/10.1016/j.jtbi.2021.110729</a>","ama":"Khudiakova K, Neretina TY, Kondrashov AS. Two linked loci under mutation-selection balance and Muller’s ratchet. <i>Journal of Theoretical Biology</i>. 2021;524. doi:<a href=\"https://doi.org/10.1016/j.jtbi.2021.110729\">10.1016/j.jtbi.2021.110729</a>","mla":"Khudiakova, Kseniia, et al. “Two Linked Loci under Mutation-Selection Balance and Muller’s Ratchet.” <i>Journal of Theoretical Biology</i>, vol. 524, 110729, Elsevier, 2021, doi:<a href=\"https://doi.org/10.1016/j.jtbi.2021.110729\">10.1016/j.jtbi.2021.110729</a>.","ista":"Khudiakova K, Neretina TY, Kondrashov AS. 2021. Two linked loci under mutation-selection balance and Muller’s ratchet. Journal of Theoretical Biology. 524, 110729.","short":"K. Khudiakova, T.Y. Neretina, A.S. Kondrashov, Journal of Theoretical Biology 524 (2021).","chicago":"Khudiakova, Kseniia, Tatiana Yu. Neretina, and Alexey S. Kondrashov. “Two Linked Loci under Mutation-Selection Balance and Muller’s Ratchet.” <i>Journal of Theoretical Biology</i>. Elsevier, 2021. <a href=\"https://doi.org/10.1016/j.jtbi.2021.110729\">https://doi.org/10.1016/j.jtbi.2021.110729</a>."},"author":[{"orcid":"0000-0002-6246-1465","full_name":"Khudiakova, Kseniia","first_name":"Kseniia","id":"4E6DC800-AE37-11E9-AC72-31CAE5697425","last_name":"Khudiakova"},{"first_name":"Tatiana Yu.","last_name":"Neretina","full_name":"Neretina, Tatiana Yu."},{"first_name":"Alexey S.","last_name":"Kondrashov","full_name":"Kondrashov, Alexey S."}],"publication_status":"published","title":"Two linked loci under mutation-selection balance and Muller’s ratchet","abstract":[{"lang":"eng","text":"We report the complete analysis of a deterministic model of deleterious mutations and negative selection against them at two haploid loci without recombination. As long as mutation is a weaker force than selection, mutant alleles remain rare at the only stable equilibrium, and otherwise, a variety of dynamics are possible. If the mutation-free genotype is absent, generally the only stable equilibrium is the one that corresponds to fixation of the mutant allele at the locus where it is less deleterious. This result suggests that fixation of a deleterious allele that follows a click of the Muller’s ratchet is governed by natural selection, instead of random drift."}],"status":"public","month":"04","article_number":"110729","article_type":"original","publisher":"Elsevier","volume":524,"article_processing_charge":"No","date_created":"2021-05-12T05:58:42Z","oa":1,"quality_controlled":"1","publication":"Journal of Theoretical Biology","publication_identifier":{"issn":["0022-5193"]}},{"doi":"10.7554/elife.54383","pmid":1,"year":"2020","day":"08","file":[{"file_size":4399825,"checksum":"f8b3821349a194050be02570d8fe7d4b","file_name":"2020_eLife_Bersini.pdf","content_type":"application/pdf","date_updated":"2022-04-08T06:53:10Z","relation":"main_file","file_id":"11132","success":1,"creator":"dernst","date_created":"2022-04-08T06:53:10Z","access_level":"open_access"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"external_id":{"pmid":["32896271"]},"date_updated":"2024-10-14T11:17:02Z","date_published":"2020-09-08T00:00:00Z","language":[{"iso":"eng"}],"scopus_import":"1","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"has_accepted_license":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","type":"journal_article","oa_version":"Published Version","_id":"11055","intvolume":"         9","author":[{"last_name":"Bersini","first_name":"Simone","full_name":"Bersini, Simone"},{"first_name":"Roberta","last_name":"Schulte","full_name":"Schulte, Roberta"},{"last_name":"Huang","first_name":"Ling","full_name":"Huang, Ling"},{"full_name":"Tsai, Hannah","last_name":"Tsai","first_name":"Hannah"},{"first_name":"Martin W","last_name":"HETZER","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","full_name":"HETZER, Martin W","orcid":"0000-0002-2111-992X"}],"citation":{"chicago":"Bersini, Simone, Roberta Schulte, Ling Huang, Hannah Tsai, and Martin Hetzer. “Direct Reprogramming of Human Smooth Muscle and Vascular Endothelial Cells Reveals Defects Associated with Aging and Hutchinson-Gilford Progeria Syndrome.” <i>ELife</i>. eLife Sciences Publications, 2020. <a href=\"https://doi.org/10.7554/elife.54383\">https://doi.org/10.7554/elife.54383</a>.","short":"S. Bersini, R. Schulte, L. Huang, H. Tsai, M. Hetzer, ELife 9 (2020).","ista":"Bersini S, Schulte R, Huang L, Tsai H, Hetzer M. 2020. Direct reprogramming of human smooth muscle and vascular endothelial cells reveals defects associated with aging and Hutchinson-Gilford progeria syndrome. eLife. 9, e54383.","mla":"Bersini, Simone, et al. “Direct Reprogramming of Human Smooth Muscle and Vascular Endothelial Cells Reveals Defects Associated with Aging and Hutchinson-Gilford Progeria Syndrome.” <i>ELife</i>, vol. 9, e54383, eLife Sciences Publications, 2020, doi:<a href=\"https://doi.org/10.7554/elife.54383\">10.7554/elife.54383</a>.","ama":"Bersini S, Schulte R, Huang L, Tsai H, Hetzer M. Direct reprogramming of human smooth muscle and vascular endothelial cells reveals defects associated with aging and Hutchinson-Gilford progeria syndrome. <i>eLife</i>. 2020;9. doi:<a href=\"https://doi.org/10.7554/elife.54383\">10.7554/elife.54383</a>","apa":"Bersini, S., Schulte, R., Huang, L., Tsai, H., &#38; Hetzer, M. (2020). Direct reprogramming of human smooth muscle and vascular endothelial cells reveals defects associated with aging and Hutchinson-Gilford progeria syndrome. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.54383\">https://doi.org/10.7554/elife.54383</a>","ieee":"S. Bersini, R. Schulte, L. Huang, H. Tsai, and M. Hetzer, “Direct reprogramming of human smooth muscle and vascular endothelial cells reveals defects associated with aging and Hutchinson-Gilford progeria syndrome,” <i>eLife</i>, vol. 9. eLife Sciences Publications, 2020."},"publication_status":"published","title":"Direct reprogramming of human smooth muscle and vascular endothelial cells reveals defects associated with aging and Hutchinson-Gilford progeria syndrome","extern":"1","status":"public","abstract":[{"text":"Vascular dysfunctions are a common feature of multiple age-related diseases. However, modeling healthy and pathological aging of the human vasculature represents an unresolved experimental challenge. Here, we generated induced vascular endothelial cells (iVECs) and smooth muscle cells (iSMCs) by direct reprogramming of healthy human fibroblasts from donors of different ages and Hutchinson-Gilford Progeria Syndrome (HGPS) patients. iVECs induced from old donors revealed upregulation of GSTM1 and PALD1, genes linked to oxidative stress, inflammation and endothelial junction stability, as vascular aging markers. A functional assay performed on PALD1 KD VECs demonstrated a recovery in vascular permeability. We found that iSMCs from HGPS donors overexpressed bone morphogenetic protein (BMP)−4, which plays a key role in both vascular calcification and endothelial barrier damage observed in HGPS. Strikingly, BMP4 concentrations are higher in serum from HGPS vs. age-matched mice. Furthermore, targeting BMP4 with blocking antibody recovered the functionality of the vascular barrier in vitro, hence representing a potential future therapeutic strategy to limit cardiovascular dysfunction in HGPS. These results show that iVECs and iSMCs retain disease-related signatures, allowing modeling of vascular aging and HGPS in vitro.","lang":"eng"}],"month":"09","article_number":"e54383","ddc":["570"],"publisher":"eLife Sciences Publications","article_type":"original","file_date_updated":"2022-04-08T06:53:10Z","article_processing_charge":"No","volume":9,"quality_controlled":"1","oa":1,"date_created":"2022-04-07T07:43:48Z","publication":"eLife","publication_identifier":{"issn":["2050-084X"]}},{"doi":"10.7554/elife.55275","day":"26","year":"2020","date_updated":"2024-03-25T12:25:02Z","date_published":"2020-02-26T00:00:00Z","main_file_link":[{"url":"https://doi.org/10.7554/eLife.55275","open_access":"1"}],"language":[{"iso":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","scopus_import":"1","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"type":"journal_article","oa_version":"Published Version","_id":"15153","intvolume":"         9","publication_status":"published","citation":{"mla":"Fribourgh, Jennifer L., et al. “Dynamics at the Serine Loop Underlie Differential Affinity of Cryptochromes for CLOCK:BMAL1 to Control Circadian Timing.” <i>ELife</i>, vol. 9, 55275, eLife Sciences Publications, 2020, doi:<a href=\"https://doi.org/10.7554/elife.55275\">10.7554/elife.55275</a>.","chicago":"Fribourgh, Jennifer L, Ashutosh Srivastava, Colby R Sandate, Alicia K. Michael, Peter L Hsu, Christin Rakers, Leslee T Nguyen, et al. “Dynamics at the Serine Loop Underlie Differential Affinity of Cryptochromes for CLOCK:BMAL1 to Control Circadian Timing.” <i>ELife</i>. eLife Sciences Publications, 2020. <a href=\"https://doi.org/10.7554/elife.55275\">https://doi.org/10.7554/elife.55275</a>.","short":"J.L. Fribourgh, A. Srivastava, C.R. Sandate, A.K. Michael, P.L. Hsu, C. Rakers, L.T. Nguyen, M.R. Torgrimson, G.C.G. Parico, S. Tripathi, N. Zheng, G.C. Lander, T. Hirota, F. Tama, C.L. Partch, ELife 9 (2020).","ista":"Fribourgh JL, Srivastava A, Sandate CR, Michael AK, Hsu PL, Rakers C, Nguyen LT, Torgrimson MR, Parico GCG, Tripathi S, Zheng N, Lander GC, Hirota T, Tama F, Partch CL. 2020. Dynamics at the serine loop underlie differential affinity of cryptochromes for CLOCK:BMAL1 to control circadian timing. eLife. 9, 55275.","ama":"Fribourgh JL, Srivastava A, Sandate CR, et al. Dynamics at the serine loop underlie differential affinity of cryptochromes for CLOCK:BMAL1 to control circadian timing. <i>eLife</i>. 2020;9. doi:<a href=\"https://doi.org/10.7554/elife.55275\">10.7554/elife.55275</a>","ieee":"J. L. Fribourgh <i>et al.</i>, “Dynamics at the serine loop underlie differential affinity of cryptochromes for CLOCK:BMAL1 to control circadian timing,” <i>eLife</i>, vol. 9. eLife Sciences Publications, 2020.","apa":"Fribourgh, J. L., Srivastava, A., Sandate, C. R., Michael, A. K., Hsu, P. L., Rakers, C., … Partch, C. L. (2020). Dynamics at the serine loop underlie differential affinity of cryptochromes for CLOCK:BMAL1 to control circadian timing. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.55275\">https://doi.org/10.7554/elife.55275</a>"},"author":[{"first_name":"Jennifer L","last_name":"Fribourgh","full_name":"Fribourgh, Jennifer L"},{"full_name":"Srivastava, Ashutosh","last_name":"Srivastava","first_name":"Ashutosh"},{"last_name":"Sandate","first_name":"Colby R","full_name":"Sandate, Colby R"},{"id":"6437c950-2a03-11ee-914d-d6476dd7b75c","last_name":"Michael","first_name":"Alicia Kathleen","full_name":"Michael, Alicia Kathleen"},{"last_name":"Hsu","first_name":"Peter L","full_name":"Hsu, Peter L"},{"full_name":"Rakers, Christin","first_name":"Christin","last_name":"Rakers"},{"first_name":"Leslee T","last_name":"Nguyen","full_name":"Nguyen, Leslee T"},{"full_name":"Torgrimson, Megan R","first_name":"Megan R","last_name":"Torgrimson"},{"first_name":"Gian Carlo G","last_name":"Parico","full_name":"Parico, Gian Carlo G"},{"full_name":"Tripathi, Sarvind","first_name":"Sarvind","last_name":"Tripathi"},{"first_name":"Ning","last_name":"Zheng","full_name":"Zheng, Ning"},{"full_name":"Lander, Gabriel C","last_name":"Lander","first_name":"Gabriel C"},{"first_name":"Tsuyoshi","last_name":"Hirota","full_name":"Hirota, Tsuyoshi"},{"full_name":"Tama, Florence","last_name":"Tama","first_name":"Florence"},{"first_name":"Carrie L","last_name":"Partch","full_name":"Partch, Carrie L"}],"extern":"1","title":"Dynamics at the serine loop underlie differential affinity of cryptochromes for CLOCK:BMAL1 to control circadian timing","abstract":[{"lang":"eng","text":"Mammalian circadian rhythms are generated by a transcription-based feedback loop in which CLOCK:BMAL1 drives transcription of its repressors (PER1/2, CRY1/2), which ultimately interact with CLOCK:BMAL1 to close the feedback loop with ~24 hr periodicity. Here we pinpoint a key difference between CRY1 and CRY2 that underlies their differential strengths as transcriptional repressors. Both cryptochromes bind the BMAL1 transactivation domain similarly to sequester it from coactivators and repress CLOCK:BMAL1 activity. However, we find that CRY1 is recruited with much higher affinity to the PAS domain core of CLOCK:BMAL1, allowing it to serve as a stronger repressor that lengthens circadian period. We discovered a dynamic serine-rich loop adjacent to the secondary pocket in the photolyase homology region (PHR) domain that regulates differential binding of cryptochromes to the PAS domain core of CLOCK:BMAL1. Notably, binding of the co-repressor PER2 remodels the serine loop of CRY2, making it more CRY1-like and enhancing its affinity for CLOCK:BMAL1."}],"status":"public","month":"02","article_number":"55275","article_type":"original","publisher":"eLife Sciences Publications","article_processing_charge":"No","volume":9,"oa":1,"date_created":"2024-03-21T07:55:12Z","quality_controlled":"1","publication":"eLife","publication_identifier":{"issn":["2050-084X"]}},{"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"external_id":{"pmid":["31599721"]},"file":[{"content_type":"application/pdf","checksum":"1e8672a1e9c3dc0a2d3d0dad89673616","file_name":"2019_eLife_Buchwalter.pdf","file_size":6984654,"relation":"main_file","date_updated":"2022-04-08T08:18:01Z","success":1,"file_id":"11138","access_level":"open_access","date_created":"2022-04-08T08:18:01Z","creator":"dernst"}],"date_published":"2019-10-10T00:00:00Z","date_updated":"2024-10-14T12:08:36Z","doi":"10.7554/elife.49796","pmid":1,"year":"2019","day":"10","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"scopus_import":"1","related_material":{"record":[{"id":"13079","relation":"research_data","status":"public"}]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","has_accepted_license":"1","language":[{"iso":"eng"}],"_id":"11060","intvolume":"         8","type":"journal_article","oa_version":"Published Version","citation":{"ieee":"A. Buchwalter, R. Schulte, H. Tsai, J. Capitanio, and M. Hetzer, “Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress,” <i>eLife</i>, vol. 8. eLife Sciences Publications, 2019.","apa":"Buchwalter, A., Schulte, R., Tsai, H., Capitanio, J., &#38; Hetzer, M. (2019). Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.49796\">https://doi.org/10.7554/elife.49796</a>","ama":"Buchwalter A, Schulte R, Tsai H, Capitanio J, Hetzer M. Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress. <i>eLife</i>. 2019;8. doi:<a href=\"https://doi.org/10.7554/elife.49796\">10.7554/elife.49796</a>","ista":"Buchwalter A, Schulte R, Tsai H, Capitanio J, Hetzer M. 2019. Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress. eLife. 8, e49796.","short":"A. Buchwalter, R. Schulte, H. Tsai, J. Capitanio, M. Hetzer, ELife 8 (2019).","chicago":"Buchwalter, Abigail, Roberta Schulte, Hsiao Tsai, Juliana Capitanio, and Martin Hetzer. “Selective Clearance of the Inner Nuclear Membrane Protein Emerin by Vesicular Transport during ER Stress.” <i>ELife</i>. eLife Sciences Publications, 2019. <a href=\"https://doi.org/10.7554/elife.49796\">https://doi.org/10.7554/elife.49796</a>.","mla":"Buchwalter, Abigail, et al. “Selective Clearance of the Inner Nuclear Membrane Protein Emerin by Vesicular Transport during ER Stress.” <i>ELife</i>, vol. 8, e49796, eLife Sciences Publications, 2019, doi:<a href=\"https://doi.org/10.7554/elife.49796\">10.7554/elife.49796</a>."},"author":[{"full_name":"Buchwalter, Abigail","first_name":"Abigail","last_name":"Buchwalter"},{"full_name":"Schulte, Roberta","last_name":"Schulte","first_name":"Roberta"},{"full_name":"Tsai, Hsiao","first_name":"Hsiao","last_name":"Tsai"},{"full_name":"Capitanio, Juliana","first_name":"Juliana","last_name":"Capitanio"},{"first_name":"Martin W","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","last_name":"HETZER","orcid":"0000-0002-2111-992X","full_name":"HETZER, Martin W"}],"publication_status":"published","title":"Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress","extern":"1","status":"public","abstract":[{"lang":"eng","text":"The inner nuclear membrane (INM) is a subdomain of the endoplasmic reticulum (ER) that is gated by the nuclear pore complex. It is unknown whether proteins of the INM and ER are degraded through shared or distinct pathways in mammalian cells. We applied dynamic proteomics to profile protein half-lives and report that INM and ER residents turn over at similar rates, indicating that the INM’s unique topology is not a barrier to turnover. Using a microscopy approach, we observed that the proteasome can degrade INM proteins in situ. However, we also uncovered evidence for selective, vesicular transport-mediated turnover of a single INM protein, emerin, that is potentiated by ER stress. Emerin is rapidly cleared from the INM by a mechanism that requires emerin’s LEM domain to mediate vesicular trafficking to lysosomes. This work demonstrates that the INM can be dynamically remodeled in response to environmental inputs."}],"month":"10","article_processing_charge":"No","volume":8,"quality_controlled":"1","date_created":"2022-04-07T07:45:02Z","oa":1,"ddc":["570"],"article_number":"e49796","publisher":"eLife Sciences Publications","file_date_updated":"2022-04-08T08:18:01Z","article_type":"original","publication_identifier":{"issn":["2050-084X"]},"publication":"eLife"},{"month":"05","status":"public","abstract":[{"lang":"eng","text":"Transposable elements (TEs), the movement of which can damage the genome, are epigenetically silenced in eukaryotes. Intriguingly, TEs are activated in the sperm companion cell – vegetative cell (VC) – of the flowering plant Arabidopsis thaliana. However, the extent and mechanism of this activation are unknown. Here we show that about 100 heterochromatic TEs are activated in VCs, mostly by DEMETER-catalyzed DNA demethylation. We further demonstrate that DEMETER access to some of these TEs is permitted by the natural depletion of linker histone H1 in VCs. Ectopically expressed H1 suppresses TEs in VCs by reducing DNA demethylation and via a methylation-independent mechanism. We demonstrate that H1 is required for heterochromatin condensation in plant cells and show that H1 overexpression creates heterochromatic foci in the VC progenitor cell. Taken together, our results demonstrate that the natural depletion of H1 during male gametogenesis facilitates DEMETER-directed DNA demethylation, heterochromatin relaxation, and TE activation."}],"publisher":"eLife Sciences Publications","article_type":"original","file_date_updated":"2023-02-07T09:42:46Z","ddc":["580"],"article_number":"42530","quality_controlled":"1","date_created":"2023-01-16T09:17:21Z","oa":1,"volume":8,"article_processing_charge":"No","publication":"eLife","publication_identifier":{"issn":["2050-084X"]},"year":"2019","day":"28","doi":"10.7554/elife.42530","date_published":"2019-05-28T00:00:00Z","date_updated":"2025-01-14T14:31:41Z","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"external_id":{"unknown":["31135340"]},"file":[{"relation":"main_file","date_updated":"2023-02-07T09:42:46Z","file_name":"2019_elife_He.pdf","checksum":"ea6b89c20d59e5eb3646916fe5d568ad","content_type":"application/pdf","file_size":2493837,"access_level":"open_access","creator":"alisjak","date_created":"2023-02-07T09:42:46Z","success":1,"file_id":"12525"}],"acknowledgement":"We thank David Twell for the pDONR-P4-P1R-pLAT52 and pDONR-P2R-P3-mRFP vectors, the John Innes Centre Bioimaging Facility (Elaine Barclay and Grant Calder) for their assistance with microscopy, and the Norwich BioScience Institute Partnership Computing infrastructure for Science Group for High Performance Computing resources. This work was funded by a Biotechnology and Biological Sciences Research Council (BBSRC) David Phillips Fellowship (BB/L025043/1; SH, JZ and XF), a European Research Council Starting Grant ('SexMeth' 804981; XF) and a Grant to Exceptional Researchers by the Gatsby Charitable Foundation (SH and XF).","language":[{"iso":"eng"}],"scopus_import":"1","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"has_accepted_license":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"Published Version","type":"journal_article","intvolume":"         8","department":[{"_id":"XiFe"}],"_id":"12192","title":"Natural depletion of histone H1 in sex cells causes DNA demethylation, heterochromatin decondensation and transposon activation","extern":"1","author":[{"last_name":"He","first_name":"Shengbo","full_name":"He, Shengbo"},{"full_name":"Vickers, Martin","last_name":"Vickers","first_name":"Martin"},{"last_name":"Zhang","first_name":"Jingyi","full_name":"Zhang, Jingyi"},{"last_name":"Feng","id":"e0164712-22ee-11ed-b12a-d80fcdf35958","first_name":"Xiaoqi","full_name":"Feng, Xiaoqi","orcid":"0000-0002-4008-1234"}],"publication_status":"published","citation":{"chicago":"He, Shengbo, Martin Vickers, Jingyi Zhang, and Xiaoqi Feng. “Natural Depletion of Histone H1 in Sex Cells Causes DNA Demethylation, Heterochromatin Decondensation and Transposon Activation.” <i>ELife</i>. eLife Sciences Publications, 2019. <a href=\"https://doi.org/10.7554/elife.42530\">https://doi.org/10.7554/elife.42530</a>.","short":"S. He, M. Vickers, J. Zhang, X. Feng, ELife 8 (2019).","ista":"He S, Vickers M, Zhang J, Feng X. 2019. Natural depletion of histone H1 in sex cells causes DNA demethylation, heterochromatin decondensation and transposon activation. eLife. 8, 42530.","mla":"He, Shengbo, et al. “Natural Depletion of Histone H1 in Sex Cells Causes DNA Demethylation, Heterochromatin Decondensation and Transposon Activation.” <i>ELife</i>, vol. 8, 42530, eLife Sciences Publications, 2019, doi:<a href=\"https://doi.org/10.7554/elife.42530\">10.7554/elife.42530</a>.","ama":"He S, Vickers M, Zhang J, Feng X. Natural depletion of histone H1 in sex cells causes DNA demethylation, heterochromatin decondensation and transposon activation. <i>eLife</i>. 2019;8. doi:<a href=\"https://doi.org/10.7554/elife.42530\">10.7554/elife.42530</a>","ieee":"S. He, M. Vickers, J. Zhang, and X. Feng, “Natural depletion of histone H1 in sex cells causes DNA demethylation, heterochromatin decondensation and transposon activation,” <i>eLife</i>, vol. 8. eLife Sciences Publications, 2019.","apa":"He, S., Vickers, M., Zhang, J., &#38; Feng, X. (2019). Natural depletion of histone H1 in sex cells causes DNA demethylation, heterochromatin decondensation and transposon activation. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.42530\">https://doi.org/10.7554/elife.42530</a>"}},{"oa":1,"date_created":"2019-09-19T08:19:44Z","article_processing_charge":"No","publisher":"Institute of Science and Technology Austria","file_date_updated":"2020-10-17T22:30:03Z","ddc":["570"],"page":"171","month":"07","status":"public","abstract":[{"lang":"eng","text":"While cells of mesenchymal or epithelial origin perform their effector functions in a purely anchorage dependent manner, cells derived from the hematopoietic lineage are not committed to operate only within a specific niche. Instead, these cells are able to function autonomously of the molecular composition in a broad range of tissue compartments. By this means, cells of the hematopoietic lineage retain the capacity to disseminate into connective tissue and recirculate between organs, building the foundation for essential processes such as tissue regeneration or immune surveillance. \r\nCells of the immune system, specifically leukocytes, are extraordinarily good at performing this task. These cells are able to flexibly shift their mode of migration between an adhesion-mediated and an adhesion-independent manner, instantaneously accommodating for any changes in molecular composition of the external scaffold. The key component driving directed leukocyte migration is the chemokine receptor 7, which guides the cell along gradients of chemokine ligand. Therefore, the physical destination of migrating leukocytes is purely deterministic, i.e. given by global directional cues such as chemokine gradients. \r\nNevertheless, these cells typically reside in three-dimensional scaffolds of inhomogeneous complexity, raising the question whether cells are able to locally discriminate between multiple optional migration routes. Current literature provides evidence that leukocytes, specifically dendritic cells, do indeed probe their surrounding by virtue of multiple explorative protrusions. However, it remains enigmatic how these cells decide which one is the more favorable route to follow and what are the key players involved in performing this task. Due to the heterogeneous environment of most tissues, and the vast adaptability of migrating leukocytes, at this time it is not clear to what extent leukocytes are able to optimize their migratory strategy by adapting their level of adhesiveness. And, given the fact that leukocyte migration is characterized by branched cell shapes in combination with high migration velocities, it is reasonable to assume that these cells require fine tuned shape maintenance mechanisms that tightly coordinate protrusion and adhesion dynamics in a spatiotemporal manner. \r\nTherefore, this study aimed to elucidate how rapidly migrating leukocytes opt for an ideal migratory path while maintaining a continuous cell shape and balancing adhesive forces to efficiently navigate through complex microenvironments. \r\nThe results of this study unraveled a role for the microtubule cytoskeleton in promoting the decision making process during path finding and for the first time point towards a microtubule-mediated function in cell shape maintenance of highly ramified cells such as dendritic cells. Furthermore, we found that migrating low-adhesive leukocytes are able to instantaneously adapt to increased tensile load by engaging adhesion receptors. This response was only occurring tangential to the substrate while adhesive properties in the vertical direction were not increased. As leukocytes are primed for rapid migration velocities, these results demonstrate that leukocyte integrins are able to confer a high level of traction forces parallel to the cell membrane along the direction of migration without wasting energy in gluing the cell to the substrate. \r\nThus, the data in the here presented thesis provide new insights into the pivotal role of cytoskeletal dynamics and the mechanisms of force transduction during leukocyte migration. \r\nThereby the here presented results help to further define fundamental principles underlying leukocyte migration and open up potential therapeutic avenues of clinical relevance.\r\n"}],"publication_identifier":{"eissn":["2663-337X"],"isbn":["978-3-99078-002-2"]},"degree_awarded":"PhD","related_material":{"record":[{"status":"public","id":"6877","relation":"part_of_dissertation"},{"id":"6328","relation":"part_of_dissertation","status":"public"},{"id":"15","relation":"part_of_dissertation","status":"public"}],"link":[{"relation":"press_release","url":"https://ist.ac.at/en/news/feeling-like-a-cell/"}]},"keyword":["cell biology","immunology","leukocyte","migration","microfluidics"],"has_accepted_license":"1","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","language":[{"iso":"eng"}],"alternative_title":["ISTA Thesis"],"date_updated":"2026-06-18T17:44:11Z","date_published":"2019-07-24T00:00:00Z","file":[{"file_id":"6950","access_level":"closed","date_created":"2019-10-15T05:28:42Z","creator":"akopf","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","checksum":"00d100d6468e31e583051e0a006b640c","file_name":"Kopf_PhD_Thesis.docx","embargo_to":"open_access","file_size":74735267,"relation":"source_file","date_updated":"2020-10-17T22:30:03Z"},{"file_id":"6951","creator":"akopf","date_created":"2019-10-15T05:28:47Z","access_level":"open_access","file_size":52787224,"embargo":"2020-10-16","file_name":"Kopf_PhD_Thesis1.pdf","checksum":"5d1baa899993ae6ca81aebebe1797000","content_type":"application/pdf","date_updated":"2020-10-17T22:30:03Z","relation":"main_file"}],"year":"2019","day":"24","doi":"10.15479/AT:ISTA:6891","title":"The implication of cytoskeletal dynamics on leukocyte migration","OA_place":"publisher","project":[{"name":"Nano-Analytics of Cellular Systems","_id":"265E2996-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"W01250-B20"}],"corr_author":"1","citation":{"ista":"Kopf A. 2019. The implication of cytoskeletal dynamics on leukocyte migration. Institute of Science and Technology Austria.","chicago":"Kopf, Aglaja. “The Implication of Cytoskeletal Dynamics on Leukocyte Migration.” Institute of Science and Technology Austria, 2019. <a href=\"https://doi.org/10.15479/AT:ISTA:6891\">https://doi.org/10.15479/AT:ISTA:6891</a>.","short":"A. Kopf, The Implication of Cytoskeletal Dynamics on Leukocyte Migration, Institute of Science and Technology Austria, 2019.","mla":"Kopf, Aglaja. <i>The Implication of Cytoskeletal Dynamics on Leukocyte Migration</i>. Institute of Science and Technology Austria, 2019, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6891\">10.15479/AT:ISTA:6891</a>.","apa":"Kopf, A. (2019). <i>The implication of cytoskeletal dynamics on leukocyte migration</i>. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:6891\">https://doi.org/10.15479/AT:ISTA:6891</a>","ieee":"A. Kopf, “The implication of cytoskeletal dynamics on leukocyte migration,” Institute of Science and Technology Austria, 2019.","ama":"Kopf A. The implication of cytoskeletal dynamics on leukocyte migration. 2019. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:6891\">10.15479/AT:ISTA:6891</a>"},"author":[{"full_name":"Kopf, Aglaja","orcid":"0000-0002-2187-6656","last_name":"Kopf","id":"31DAC7B6-F248-11E8-B48F-1D18A9856A87","first_name":"Aglaja"}],"publication_status":"published","supervisor":[{"first_name":"Michael K","last_name":"Sixt","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179"}],"department":[{"_id":"MiSi"}],"_id":"6891","oa_version":"Published Version","type":"dissertation"},{"publication_identifier":{"issn":["2050-084X"]},"publication":"eLife","article_processing_charge":"Yes","volume":6,"oa":1,"date_created":"2024-03-21T07:55:36Z","quality_controlled":"1","article_number":"26163","article_type":"original","publisher":"eLife Sciences Publications","abstract":[{"lang":"eng","text":"Biofilm formation is critical for the infection cycle of Vibrio cholerae. Vibrio exopolysaccharides (VPS) and the matrix proteins RbmA, Bap1 and RbmC are required for the development of biofilm architecture. We demonstrate that RbmA binds VPS directly and uses a binary structural switch within its first fibronectin type III (FnIII-1) domain to control RbmA structural dynamics and the formation of VPS-dependent higher-order structures. The structural switch in FnIII-1 regulates interactions in trans with the FnIII-2 domain, leading to open (monomeric) or closed (dimeric) interfaces. The ability of RbmA to switch between open and closed states is important for V. cholerae biofilm formation, as RbmA variants with switches that are locked in either of the two states lead to biofilms with altered architecture and structural integrity."}],"status":"public","month":"08","publication_status":"published","citation":{"ama":"Fong JC, Rogers A, Michael AK, et al. Structural dynamics of RbmA governs plasticity of Vibrio cholerae biofilms. <i>eLife</i>. 2017;6. doi:<a href=\"https://doi.org/10.7554/elife.26163\">10.7554/elife.26163</a>","ieee":"J. C. Fong <i>et al.</i>, “Structural dynamics of RbmA governs plasticity of Vibrio cholerae biofilms,” <i>eLife</i>, vol. 6. eLife Sciences Publications, 2017.","apa":"Fong, J. C., Rogers, A., Michael, A. K., Parsley, N. C., Cornell, W.-C., Lin, Y.-C., … Yildiz, F. H. (2017). Structural dynamics of RbmA governs plasticity of Vibrio cholerae biofilms. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.26163\">https://doi.org/10.7554/elife.26163</a>","short":"J.C. Fong, A. Rogers, A.K. Michael, N.C. Parsley, W.-C. Cornell, Y.-C. Lin, P.K. Singh, R. Hartmann, K. Drescher, E. Vinogradov, L.E. Dietrich, C.L. Partch, F.H. Yildiz, ELife 6 (2017).","chicago":"Fong, Jiunn CN, Andrew Rogers, Alicia K. Michael, Nicole C Parsley, William-Cole Cornell, Yu-Cheng Lin, Praveen K Singh, et al. “Structural Dynamics of RbmA Governs Plasticity of Vibrio Cholerae Biofilms.” <i>ELife</i>. eLife Sciences Publications, 2017. <a href=\"https://doi.org/10.7554/elife.26163\">https://doi.org/10.7554/elife.26163</a>.","ista":"Fong JC, Rogers A, Michael AK, Parsley NC, Cornell W-C, Lin Y-C, Singh PK, Hartmann R, Drescher K, Vinogradov E, Dietrich LE, Partch CL, Yildiz FH. 2017. Structural dynamics of RbmA governs plasticity of Vibrio cholerae biofilms. eLife. 6, 26163.","mla":"Fong, Jiunn CN, et al. “Structural Dynamics of RbmA Governs Plasticity of Vibrio Cholerae Biofilms.” <i>ELife</i>, vol. 6, 26163, eLife Sciences Publications, 2017, doi:<a href=\"https://doi.org/10.7554/elife.26163\">10.7554/elife.26163</a>."},"author":[{"full_name":"Fong, Jiunn CN","first_name":"Jiunn CN","last_name":"Fong"},{"first_name":"Andrew","last_name":"Rogers","full_name":"Rogers, Andrew"},{"first_name":"Alicia Kathleen","id":"6437c950-2a03-11ee-914d-d6476dd7b75c","last_name":"Michael","full_name":"Michael, Alicia Kathleen"},{"last_name":"Parsley","first_name":"Nicole C","full_name":"Parsley, Nicole C"},{"first_name":"William-Cole","last_name":"Cornell","full_name":"Cornell, William-Cole"},{"first_name":"Yu-Cheng","last_name":"Lin","full_name":"Lin, Yu-Cheng"},{"full_name":"Singh, Praveen K","first_name":"Praveen K","last_name":"Singh"},{"full_name":"Hartmann, Raimo","first_name":"Raimo","last_name":"Hartmann"},{"full_name":"Drescher, Knut","last_name":"Drescher","first_name":"Knut"},{"full_name":"Vinogradov, Evgeny","first_name":"Evgeny","last_name":"Vinogradov"},{"full_name":"Dietrich, Lars EP","first_name":"Lars EP","last_name":"Dietrich"},{"first_name":"Carrie L","last_name":"Partch","full_name":"Partch, Carrie L"},{"full_name":"Yildiz, Fitnat H","first_name":"Fitnat H","last_name":"Yildiz"}],"title":"Structural dynamics of RbmA governs plasticity of Vibrio cholerae biofilms","extern":"1","_id":"15154","intvolume":"         6","type":"journal_article","oa_version":"Published Version","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","scopus_import":"1","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"main_file_link":[{"open_access":"1","url":"https://doi.org/10.7554/eLife.26163"}],"language":[{"iso":"eng"}],"external_id":{"pmid":["28762945"]},"date_updated":"2024-03-25T12:22:54Z","date_published":"2017-08-01T00:00:00Z","doi":"10.7554/elife.26163","day":"01","year":"2017","pmid":1},{"language":[{"iso":"eng"}],"main_file_link":[{"url":"https://elifesciences.org/articles/30292","open_access":"1"}],"keyword":["general immunology and microbiology","general biochemistry","genetics and molecular biology","general medicine","general neuroscience"],"scopus_import":"1","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","has_accepted_license":"1","pmid":1,"day":"09","year":"2017","doi":"10.7554/elife.30292","date_published":"2017-11-09T00:00:00Z","date_updated":"2021-11-29T09:28:14Z","external_id":{"pmid":["29119945"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"file":[{"date_created":"2021-11-29T09:07:41Z","creator":"cchlebak","access_level":"open_access","file_id":"10372","success":1,"date_updated":"2021-11-29T09:07:41Z","relation":"main_file","file_size":6120157,"content_type":"application/pdf","file_name":"2017_eLife_Helle.pdf","checksum":"c35f42dcfb007f6d6c761a27e24c26d3"}],"title":"Mechanical force induces mitochondrial fission","extern":"1","publication_status":"published","citation":{"ista":"Helle SCJ, Feng Q, Aebersold MJ, Hirt L, Grüter RR, Vahid A, Sirianni A, Mostowy S, Snedeker JG, Šarić A, Idema T, Zambelli T, Kornmann B. 2017. Mechanical force induces mitochondrial fission. eLife. 6, e30292.","short":"S.C.J. Helle, Q. Feng, M.J. Aebersold, L. Hirt, R.R. Grüter, A. Vahid, A. Sirianni, S. Mostowy, J.G. Snedeker, A. Šarić, T. Idema, T. Zambelli, B. Kornmann, ELife 6 (2017).","chicago":"Helle, Sebastian Carsten Johannes, Qian Feng, Mathias J Aebersold, Luca Hirt, Raphael R Grüter, Afshin Vahid, Andrea Sirianni, et al. “Mechanical Force Induces Mitochondrial Fission.” <i>ELife</i>. eLife Sciences Publications, 2017. <a href=\"https://doi.org/10.7554/elife.30292\">https://doi.org/10.7554/elife.30292</a>.","mla":"Helle, Sebastian Carsten Johannes, et al. “Mechanical Force Induces Mitochondrial Fission.” <i>ELife</i>, vol. 6, e30292, eLife Sciences Publications, 2017, doi:<a href=\"https://doi.org/10.7554/elife.30292\">10.7554/elife.30292</a>.","apa":"Helle, S. C. J., Feng, Q., Aebersold, M. J., Hirt, L., Grüter, R. R., Vahid, A., … Kornmann, B. (2017). Mechanical force induces mitochondrial fission. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.30292\">https://doi.org/10.7554/elife.30292</a>","ieee":"S. C. J. Helle <i>et al.</i>, “Mechanical force induces mitochondrial fission,” <i>eLife</i>, vol. 6. eLife Sciences Publications, 2017.","ama":"Helle SCJ, Feng Q, Aebersold MJ, et al. Mechanical force induces mitochondrial fission. <i>eLife</i>. 2017;6. doi:<a href=\"https://doi.org/10.7554/elife.30292\">10.7554/elife.30292</a>"},"author":[{"full_name":"Helle, Sebastian Carsten Johannes","last_name":"Helle","first_name":"Sebastian Carsten Johannes"},{"last_name":"Feng","first_name":"Qian","full_name":"Feng, Qian"},{"full_name":"Aebersold, Mathias J","last_name":"Aebersold","first_name":"Mathias J"},{"first_name":"Luca","last_name":"Hirt","full_name":"Hirt, Luca"},{"full_name":"Grüter, Raphael R","last_name":"Grüter","first_name":"Raphael R"},{"first_name":"Afshin","last_name":"Vahid","full_name":"Vahid, Afshin"},{"full_name":"Sirianni, Andrea","last_name":"Sirianni","first_name":"Andrea"},{"last_name":"Mostowy","first_name":"Serge","full_name":"Mostowy, Serge"},{"last_name":"Snedeker","first_name":"Jess G","full_name":"Snedeker, Jess G"},{"orcid":"0000-0002-7854-2139","full_name":"Šarić, Anđela","first_name":"Anđela","id":"bf63d406-f056-11eb-b41d-f263a6566d8b","last_name":"Šarić"},{"full_name":"Idema, Timon","last_name":"Idema","first_name":"Timon"},{"last_name":"Zambelli","first_name":"Tomaso","full_name":"Zambelli, Tomaso"},{"full_name":"Kornmann, Benoît","first_name":"Benoît","last_name":"Kornmann"}],"oa_version":"Published Version","type":"journal_article","intvolume":"         6","_id":"10370","publisher":"eLife Sciences Publications","file_date_updated":"2021-11-29T09:07:41Z","article_type":"original","article_number":"e30292","ddc":["572"],"quality_controlled":"1","oa":1,"date_created":"2021-11-29T08:51:38Z","volume":6,"article_processing_charge":"No","month":"11","status":"public","abstract":[{"text":"Eukaryotic cells are densely packed with macromolecular complexes and intertwining organelles, continually transported and reshaped. Intriguingly, organelles avoid clashing and entangling with each other in such limited space. Mitochondria form extensive networks constantly remodeled by fission and fusion. Here, we show that mitochondrial fission is triggered by mechanical forces. Mechano-stimulation of mitochondria – via encounter with motile intracellular pathogens, via external pressure applied by an atomic force microscope, or via cell migration across uneven microsurfaces – results in the recruitment of the mitochondrial fission machinery, and subsequent division. We propose that MFF, owing to affinity for narrow mitochondria, acts as a membrane-bound force sensor to recruit the fission machinery to mechanically strained sites. Thus, mitochondria adapt to the environment by sensing and responding to biomechanical cues. Our findings that mechanical triggers can be coupled to biochemical responses in membrane dynamics may explain how organelles orderly cohabit in the crowded cytoplasm.","lang":"eng"}],"publication":"eLife","publication_identifier":{"issn":["2050-084X"]}}]