[{"abstract":[{"text":"The plant-signaling molecule auxin triggers fast and slow cellular responses across land plants and algae. The nuclear auxin pathway mediates gene expression and controls growth and development in land plants, but this pathway is absent from algal sister groups. Several components of rapid responses have been identified in Arabidopsis, but it is unknown if these are part of a conserved mechanism. We recently identified a fast, proteome-wide phosphorylation response to auxin. Here, we show that this response occurs across 5 land plant and algal species and converges on a core group of shared targets. We found conserved rapid physiological responses to auxin in the same species and identified rapidly accelerated fibrosarcoma (RAF)-like protein kinases as central mediators of auxin-triggered phosphorylation across species. Genetic analysis connects this kinase to both auxin-triggered protein phosphorylation and rapid cellular response, thus identifying an ancient mechanism for fast auxin responses in the green lineage.","lang":"eng"}],"status":"public","ec_funded":1,"intvolume":"       187","citation":{"ama":"Kuhn A, Roosjen M, Mutte S, et al. RAF-like protein kinases mediate a deeply conserved, rapid auxin response. <i>Cell</i>. 2024;187(1):130-148.e17. doi:<a href=\"https://doi.org/10.1016/j.cell.2023.11.021\">10.1016/j.cell.2023.11.021</a>","short":"A. Kuhn, M. Roosjen, S. Mutte, S.M. Dubey, V.P. Carrillo Carrasco, S. Boeren, A. Monzer, J. Koehorst, T. Kohchi, R. Nishihama, M. Fendrych, J. Sprakel, J. Friml, D. Weijers, Cell 187 (2024) 130–148.e17.","mla":"Kuhn, Andre, et al. “RAF-like Protein Kinases Mediate a Deeply Conserved, Rapid Auxin Response.” <i>Cell</i>, vol. 187, no. 1, Elsevier, 2024, p. 130–148.e17, doi:<a href=\"https://doi.org/10.1016/j.cell.2023.11.021\">10.1016/j.cell.2023.11.021</a>.","ieee":"A. Kuhn <i>et al.</i>, “RAF-like protein kinases mediate a deeply conserved, rapid auxin response,” <i>Cell</i>, vol. 187, no. 1. Elsevier, p. 130–148.e17, 2024.","chicago":"Kuhn, Andre, Mark Roosjen, Sumanth Mutte, Shiv Mani Dubey, Vanessa Polet Carrillo Carrasco, Sjef Boeren, Aline Monzer, et al. “RAF-like Protein Kinases Mediate a Deeply Conserved, Rapid Auxin Response.” <i>Cell</i>. Elsevier, 2024. <a href=\"https://doi.org/10.1016/j.cell.2023.11.021\">https://doi.org/10.1016/j.cell.2023.11.021</a>.","apa":"Kuhn, A., Roosjen, M., Mutte, S., Dubey, S. M., Carrillo Carrasco, V. P., Boeren, S., … Weijers, D. (2024). RAF-like protein kinases mediate a deeply conserved, rapid auxin response. <i>Cell</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cell.2023.11.021\">https://doi.org/10.1016/j.cell.2023.11.021</a>","ista":"Kuhn A, Roosjen M, Mutte S, Dubey SM, Carrillo Carrasco VP, Boeren S, Monzer A, Koehorst J, Kohchi T, Nishihama R, Fendrych M, Sprakel J, Friml J, Weijers D. 2024. RAF-like protein kinases mediate a deeply conserved, rapid auxin response. Cell. 187(1), 130–148.e17."},"keyword":["General Biochemistry","Genetics and Molecular Biology"],"has_accepted_license":"1","day":"04","article_type":"original","publication_status":"published","oa":1,"title":"RAF-like protein kinases mediate a deeply conserved, rapid auxin response","month":"01","_id":"14826","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","acknowledgement":"We are grateful to Asuka Shitaku and Eri Koide for generating and sharing the Marchantia PRAF-mCitrine line and Peng-Cheng Wang for sharing the Arabidopsis raf mutant. We are grateful to our team members for discussions and helpful advice. This work was supported by funding from the Netherlands Organization for Scientific Research (NWO): VICI grant 865.14.001 and ENW-KLEIN OCENW.KLEIN.027 grants to D.W.; VENI grant VI.VENI.212.003 to A.K.; the European Research Council AdG DIRNDL (contract number 833867) to D.W.; CoG CATCH to J.S.; StG CELLONGATE (contract 803048) to M.F.; and AdG ETAP (contract 742985) to J.F.; MEXT KAKENHI grant number JP19H05675 to T.K.; JSPS KAKENHI grant number JP20H03275 to R.N.; Takeda Science Foundation to R.N.; and the Austrian Science Fund (FWF, P29988) to J.F.","department":[{"_id":"JiFr"}],"file":[{"file_name":"2024_Cell_Kuhn.pdf","file_id":"14874","date_created":"2024-01-22T13:41:41Z","content_type":"application/pdf","success":1,"date_updated":"2024-01-22T13:41:41Z","access_level":"open_access","relation":"main_file","checksum":"06fd236a9ee0b46ccb05f44695bfc34b","file_size":13194060,"creator":"dernst"}],"volume":187,"project":[{"name":"Tracing Evolution of Auxin Transport and Polarity in Plants","grant_number":"742985","_id":"261099A6-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"name":"RNA-directed DNA methylation in plant development","grant_number":"P29988","_id":"262EF96E-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"date_updated":"2024-01-22T13:43:40Z","year":"2024","date_created":"2024-01-17T12:45:40Z","page":"130-148.e17","quality_controlled":"1","pmid":1,"scopus_import":"1","publication_identifier":{"eissn":["1097-4172"],"issn":["0092-8674"]},"article_processing_charge":"Yes (in subscription journal)","tmp":{"short":"CC BY-NC (4.0)","name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","image":"/images/cc_by_nc.png"},"type":"journal_article","file_date_updated":"2024-01-22T13:41:41Z","language":[{"iso":"eng"}],"publisher":"Elsevier","doi":"10.1016/j.cell.2023.11.021","author":[{"last_name":"Kuhn","full_name":"Kuhn, Andre","first_name":"Andre"},{"first_name":"Mark","full_name":"Roosjen, Mark","last_name":"Roosjen"},{"last_name":"Mutte","full_name":"Mutte, Sumanth","first_name":"Sumanth"},{"last_name":"Dubey","first_name":"Shiv Mani","full_name":"Dubey, Shiv Mani"},{"first_name":"Vanessa Polet","full_name":"Carrillo Carrasco, Vanessa Polet","last_name":"Carrillo Carrasco"},{"last_name":"Boeren","full_name":"Boeren, Sjef","first_name":"Sjef"},{"id":"2DB5D88C-D7B3-11E9-B8FD-7907E6697425","last_name":"Monzer","first_name":"Aline","full_name":"Monzer, Aline"},{"full_name":"Koehorst, Jasper","first_name":"Jasper","last_name":"Koehorst"},{"last_name":"Kohchi","full_name":"Kohchi, Takayuki","first_name":"Takayuki"},{"last_name":"Nishihama","full_name":"Nishihama, Ryuichi","first_name":"Ryuichi"},{"first_name":"Matyas","full_name":"Fendrych, Matyas","last_name":"Fendrych","orcid":"0000-0002-9767-8699","id":"43905548-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Sprakel","full_name":"Sprakel, Joris","first_name":"Joris"},{"orcid":"0000-0002-8302-7596","id":"4159519E-F248-11E8-B48F-1D18A9856A87","last_name":"Friml","first_name":"Jiří","full_name":"Friml, Jiří"},{"last_name":"Weijers","full_name":"Weijers, Dolf","first_name":"Dolf"}],"ddc":["580"],"publication":"Cell","issue":"1","date_published":"2024-01-04T00:00:00Z","oa_version":"Published Version","license":"https://creativecommons.org/licenses/by-nc/4.0/","external_id":{"pmid":["38128538"]}},{"type":"journal_article","language":[{"iso":"eng"}],"publisher":"eLife Sciences Publications","doi":"10.7554/elife.68993","author":[{"full_name":"Adamowski, Maciek","first_name":"Maciek","last_name":"Adamowski","id":"45F536D2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6463-5257"},{"last_name":"Matijevic","full_name":"Matijevic, Ivana","first_name":"Ivana","id":"83c17ce3-15b2-11ec-abd3-f486545870bd"},{"first_name":"Jiří","full_name":"Friml, Jiří","last_name":"Friml","id":"4159519E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8302-7596"}],"ddc":["580"],"publication":"eLife","date_published":"2024-02-21T00:00:00Z","oa_version":"Published Version","volume":13,"project":[{"call_identifier":"H2020","name":"Tracing Evolution of Auxin Transport and Polarity in Plants","grant_number":"742985","_id":"261099A6-B435-11E9-9278-68D0E5697425"},{"name":"Molecular mechanisms of endocytic cargo recognition in plants","grant_number":"I03630","_id":"26538374-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"date_updated":"2024-02-28T12:29:43Z","date_created":"2024-02-27T07:10:11Z","year":"2024","quality_controlled":"1","main_file_link":[{"url":"https://doi.org/10.7554/eLife.68993","open_access":"1"}],"publication_identifier":{"issn":["2050-084X"]},"article_processing_charge":"Yes","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"article_type":"original","publication_status":"epub_ahead","oa":1,"title":"Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery","month":"02","_id":"15033","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"JiFr"}],"acknowledgement":"The authors would like to gratefully acknowledge Dr Xixi Zhang for cloning the GNL1/pDONR221 construct and for useful discussions.H2020 European Research\r\nCouncil Advanced Grant ETAP742985 to Jiří Friml, Austrian Science Fund I 3630-B25 to Jiří Friml","abstract":[{"text":"The GNOM (GN) Guanine nucleotide Exchange Factor for ARF small GTPases (ARF-GEF) is among the best studied trafficking regulators in plants, playing crucial and unique developmental roles in patterning and polarity. The current models place GN at the Golgi apparatus (GA), where it mediates secretion/recycling, and at the plasma membrane (PM) presumably contributing to clathrin-mediated endocytosis (CME). The mechanistic basis of the developmental function of GN, distinct from the other ARF-GEFs including its closest homologue GNOM-LIKE1 (GNL1), remains elusive. Insights from this study largely extend the current notions of GN function. We show that GN, but not GNL1, localizes to the cell periphery at long-lived structures distinct from clathrin-coated pits, while CME and secretion proceed normally in <jats:italic>gn</jats:italic> knockouts. The functional GN mutant variant GN<jats:sup>fewerroots</jats:sup>, absent from the GA, suggests that the cell periphery is the major site of GN action responsible for its developmental function. Following inhibition by Brefeldin A, GN, but not GNL1, relocates to the PM likely on exocytic vesicles, suggesting selective molecular associations en route to the cell periphery. A study of GN-GNL1 chimeric ARF-GEFs indicates that all GN domains contribute to the specific GN function in a partially redundant manner. Together, this study offers significant steps toward the elucidation of the mechanism underlying unique cellular and development functions of GNOM.","lang":"eng"}],"status":"public","ec_funded":1,"citation":{"mla":"Adamowski, Maciek, et al. “Developmental Patterning Function of GNOM ARF-GEF Mediated from the Cell Periphery.” <i>ELife</i>, vol. 13, eLife Sciences Publications, 2024, doi:<a href=\"https://doi.org/10.7554/elife.68993\">10.7554/elife.68993</a>.","ieee":"M. Adamowski, I. Matijevic, and J. Friml, “Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery,” <i>eLife</i>, vol. 13. eLife Sciences Publications, 2024.","ista":"Adamowski M, Matijevic I, Friml J. 2024. Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery. eLife. 13.","chicago":"Adamowski, Maciek, Ivana Matijevic, and Jiří Friml. “Developmental Patterning Function of GNOM ARF-GEF Mediated from the Cell Periphery.” <i>ELife</i>. eLife Sciences Publications, 2024. <a href=\"https://doi.org/10.7554/elife.68993\">https://doi.org/10.7554/elife.68993</a>.","apa":"Adamowski, M., Matijevic, I., &#38; Friml, J. (2024). Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.68993\">https://doi.org/10.7554/elife.68993</a>","ama":"Adamowski M, Matijevic I, Friml J. Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery. <i>eLife</i>. 2024;13. doi:<a href=\"https://doi.org/10.7554/elife.68993\">10.7554/elife.68993</a>","short":"M. Adamowski, I. Matijevic, J. Friml, ELife 13 (2024)."},"intvolume":"        13","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"has_accepted_license":"1","day":"21"},{"scopus_import":"1","publication_identifier":{"eissn":["1546-1718"],"issn":["1061-4036"]},"article_processing_charge":"No","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"volume":55,"file":[{"success":1,"date_updated":"2023-02-27T07:46:45Z","access_level":"open_access","content_type":"application/pdf","file_id":"12688","date_created":"2023-02-27T07:46:45Z","file_name":"2023_NatureGenetics_Zeller.pdf","creator":"dernst","file_size":21484855,"checksum":"6fdb8e34fbeea63edd0f2c6c2cc5823e","relation":"main_file"}],"date_updated":"2023-02-27T07:48:24Z","page":"333-345","quality_controlled":"1","date_created":"2023-01-12T12:09:09Z","year":"2023","ddc":["570","000"],"author":[{"first_name":"Peter","full_name":"Zeller, Peter","last_name":"Zeller"},{"first_name":"Jake","full_name":"Yeung, Jake","last_name":"Yeung","id":"123012b2-db30-11eb-b4d8-a35840c0551b","orcid":"0000-0003-1732-1559"},{"first_name":"Helena","full_name":"Viñas Gaza, Helena","last_name":"Viñas Gaza"},{"last_name":"de Barbanson","first_name":"Buys Anton","full_name":"de Barbanson, Buys Anton"},{"full_name":"Bhardwaj, Vivek","first_name":"Vivek","last_name":"Bhardwaj"},{"full_name":"Florescu, Maria","first_name":"Maria","last_name":"Florescu"},{"first_name":"Reinier","full_name":"van der Linden, Reinier","last_name":"van der Linden"},{"first_name":"Alexander","full_name":"van Oudenaarden, Alexander","last_name":"van Oudenaarden"}],"publication":"Nature Genetics","date_published":"2023-02-01T00:00:00Z","oa_version":"Published Version","file_date_updated":"2023-02-27T07:46:45Z","type":"journal_article","language":[{"iso":"eng"}],"publisher":"Springer Nature","doi":"10.1038/s41588-022-01260-3","intvolume":"        55","citation":{"ama":"Zeller P, Yeung J, Viñas Gaza H, et al. Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis. <i>Nature Genetics</i>. 2023;55:333-345. doi:<a href=\"https://doi.org/10.1038/s41588-022-01260-3\">10.1038/s41588-022-01260-3</a>","short":"P. Zeller, J. Yeung, H. Viñas Gaza, B.A. de Barbanson, V. Bhardwaj, M. Florescu, R. van der Linden, A. van Oudenaarden, Nature Genetics 55 (2023) 333–345.","mla":"Zeller, Peter, et al. “Single-Cell SortChIC Identifies Hierarchical Chromatin Dynamics during Hematopoiesis.” <i>Nature Genetics</i>, vol. 55, Springer Nature, 2023, pp. 333–45, doi:<a href=\"https://doi.org/10.1038/s41588-022-01260-3\">10.1038/s41588-022-01260-3</a>.","ieee":"P. Zeller <i>et al.</i>, “Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis,” <i>Nature Genetics</i>, vol. 55. Springer Nature, pp. 333–345, 2023.","apa":"Zeller, P., Yeung, J., Viñas Gaza, H., de Barbanson, B. A., Bhardwaj, V., Florescu, M., … van Oudenaarden, A. (2023). Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis. <i>Nature Genetics</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41588-022-01260-3\">https://doi.org/10.1038/s41588-022-01260-3</a>","ista":"Zeller P, Yeung J, Viñas Gaza H, de Barbanson BA, Bhardwaj V, Florescu M, van der Linden R, van Oudenaarden A. 2023. Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis. Nature Genetics. 55, 333–345.","chicago":"Zeller, Peter, Jake Yeung, Helena Viñas Gaza, Buys Anton de Barbanson, Vivek Bhardwaj, Maria Florescu, Reinier van der Linden, and Alexander van Oudenaarden. “Single-Cell SortChIC Identifies Hierarchical Chromatin Dynamics during Hematopoiesis.” <i>Nature Genetics</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1038/s41588-022-01260-3\">https://doi.org/10.1038/s41588-022-01260-3</a>."},"keyword":["Genetics"],"has_accepted_license":"1","day":"01","abstract":[{"text":"Post-translational histone modifications modulate chromatin activity to affect gene expression. How chromatin states underlie lineage choice in single cells is relatively unexplored. We develop sort-assisted single-cell chromatin immunocleavage (sortChIC) and map active (H3K4me1 and H3K4me3) and repressive (H3K27me3 and H3K9me3) histone modifications in the mouse bone marrow. During differentiation, hematopoietic stem and progenitor cells (HSPCs) acquire active chromatin states mediated by cell-type-specifying transcription factors, which are unique for each lineage. By contrast, most alterations in repressive marks during differentiation occur independent of the final cell type. Chromatin trajectory analysis shows that lineage choice at the chromatin level occurs at the progenitor stage. Joint profiling of H3K4me1 and H3K9me3 demonstrates that cell types within the myeloid lineage have distinct active chromatin but share similar myeloid-specific heterochromatin states. This implies a hierarchical regulation of chromatin during hematopoiesis: heterochromatin dynamics distinguish differentiation trajectories and lineages, while euchromatin dynamics reflect cell types within lineages.","lang":"eng"}],"status":"public","acknowledgement":"We thank A. Giladi for sharing mRNA abundance tables of cell types together with J. van den Berg for critical reading of the manuscript. We thank M. Bartosovic for sharing method comparison data. pK19pA-MN was a gift from Ulrich Laemmli (Addgene plasmid 86973, http://n2t.net/addgene:86973; RRID:Addgene_86973). Figure 8 is adopted from Hematopoiesis (human) diagram by A. Rad and M. Häggström under CC-BY-SA 3.0 license. This work was supported by European Research Council Advanced under grant ERC-AdG 742225-IntScOmics and Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO) TOP award NWO-CW 714.016.001. The SNF (P2BSP3-174991), HFSP (LT000209/2018-L) and Marie Skłodowska-Curie Actions (798573) supported P.Z. The SNF (P2ELP3_184488) and HFSP (LT000097/2019-L) supported J.Y. and the EMBO LTF (ALTF 1197–2019) supported V.B. This work is part of the Oncode Institute, which is partly financed by the Dutch Cancer Society. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.","department":[{"_id":"ScienComp"}],"article_type":"review","oa":1,"title":"Single-cell sortChIC identifies hierarchical chromatin dynamics during hematopoiesis","publication_status":"published","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"12158","month":"02"},{"ddc":["570"],"author":[{"orcid":"0000-0002-1145-9226","id":"428A94B0-F248-11E8-B48F-1D18A9856A87","first_name":"Daria","full_name":"Shipilina, Daria","last_name":"Shipilina"},{"last_name":"Pal","first_name":"Arka","full_name":"Pal, Arka","orcid":"0000-0002-4530-8469","id":"6AAB2240-CA9A-11E9-9C1A-D9D1E5697425"},{"id":"43161670-5719-11EA-8025-FABC3DDC885E","full_name":"Stankowski, Sean","first_name":"Sean","last_name":"Stankowski"},{"last_name":"Chan","full_name":"Chan, Yingguang Frank","first_name":"Yingguang Frank"},{"last_name":"Barton","first_name":"Nicholas H","full_name":"Barton, Nicholas H","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8548-5240"}],"issue":"6","publication":"Molecular Ecology","date_published":"2023-03-01T00:00:00Z","oa_version":"Published Version","external_id":{"pmid":["36433653"],"isi":["000900762000001"]},"file_date_updated":"2023-08-16T08:15:41Z","type":"journal_article","language":[{"iso":"eng"}],"publisher":"Wiley","doi":"10.1111/mec.16793","scopus_import":"1","pmid":1,"publication_identifier":{"issn":["0962-1083"],"eissn":["1365-294X"]},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"article_processing_charge":"Yes (via OA deal)","volume":32,"isi":1,"file":[{"file_name":"2023_MolecularEcology_Shipilina.pdf","date_updated":"2023-08-16T08:15:41Z","success":1,"access_level":"open_access","date_created":"2023-08-16T08:15:41Z","file_id":"14062","content_type":"application/pdf","checksum":"b10e0f8fa3dc4d72aaf77a557200978a","relation":"main_file","creator":"dernst","file_size":7144607}],"date_updated":"2023-08-16T08:18:47Z","project":[{"_id":"05959E1C-7A3F-11EA-A408-12923DDC885E","grant_number":"P32166","name":"The maintenance of alternative adaptive peaks in snapdragons"},{"name":"The Wittgenstein Prize","grant_number":"Z211","_id":"25F42A32-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"name":"Understanding the evolution of continuous genomes","grant_number":"101055327","_id":"bd6958e0-d553-11ed-ba76-86eba6a76c00"}],"quality_controlled":"1","page":"1441-1457","date_created":"2023-01-12T12:09:17Z","year":"2023","acknowledgement":"We thank the Barton group for useful discussion and feedback during the writing of this article. Comments from Roger Butlin, Molly Schumer's Group, the tskit development team, editors and three reviewers greatly improved the manuscript. Funding was provided by SCAS (Natural Sciences Programme, Knut and Alice Wallenberg Foundation), an FWF Wittgenstein grant (PT1001Z211), an FWF standalone grant (grant P 32166), and an ERC Advanced Grant. YFC was supported by the Max Planck Society and an ERC Proof of Concept Grant #101069216 (HAPLOTAGGING).","department":[{"_id":"NiBa"}],"article_type":"original","title":"On the origin and structure of haplotype blocks","oa":1,"publication_status":"published","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"03","_id":"12159","intvolume":"        32","citation":{"ama":"Shipilina D, Pal A, Stankowski S, Chan YF, Barton NH. On the origin and structure of haplotype blocks. <i>Molecular Ecology</i>. 2023;32(6):1441-1457. doi:<a href=\"https://doi.org/10.1111/mec.16793\">10.1111/mec.16793</a>","short":"D. Shipilina, A. Pal, S. Stankowski, Y.F. Chan, N.H. Barton, Molecular Ecology 32 (2023) 1441–1457.","mla":"Shipilina, Daria, et al. “On the Origin and Structure of Haplotype Blocks.” <i>Molecular Ecology</i>, vol. 32, no. 6, Wiley, 2023, pp. 1441–57, doi:<a href=\"https://doi.org/10.1111/mec.16793\">10.1111/mec.16793</a>.","ieee":"D. Shipilina, A. Pal, S. Stankowski, Y. F. Chan, and N. H. Barton, “On the origin and structure of haplotype blocks,” <i>Molecular Ecology</i>, vol. 32, no. 6. Wiley, pp. 1441–1457, 2023.","apa":"Shipilina, D., Pal, A., Stankowski, S., Chan, Y. F., &#38; Barton, N. H. (2023). On the origin and structure of haplotype blocks. <i>Molecular Ecology</i>. Wiley. <a href=\"https://doi.org/10.1111/mec.16793\">https://doi.org/10.1111/mec.16793</a>","ista":"Shipilina D, Pal A, Stankowski S, Chan YF, Barton NH. 2023. On the origin and structure of haplotype blocks. Molecular Ecology. 32(6), 1441–1457.","chicago":"Shipilina, Daria, Arka Pal, Sean Stankowski, Yingguang Frank Chan, and Nicholas H Barton. “On the Origin and Structure of Haplotype Blocks.” <i>Molecular Ecology</i>. Wiley, 2023. <a href=\"https://doi.org/10.1111/mec.16793\">https://doi.org/10.1111/mec.16793</a>."},"keyword":["Genetics","Ecology","Evolution","Behavior and Systematics"],"has_accepted_license":"1","day":"01","abstract":[{"text":"The term “haplotype block” is commonly used in the developing field of haplotype-based inference methods. We argue that the term should be defined based on the structure of the Ancestral Recombination Graph (ARG), which contains complete information on the ancestry of a sample. We use simulated examples to demonstrate key features of the relationship between haplotype blocks and ancestral structure, emphasizing the stochasticity of the processes that generate them. Even the simplest cases of neutrality or of a “hard” selective sweep produce a rich structure, often missed by commonly used statistics. We highlight a number of novel methods for inferring haplotype structure, based on the full ARG, or on a sequence of trees, and illustrate how they can be used to define haplotype blocks using an empirical data set. While the advent of new, computationally efficient methods makes it possible to apply these concepts broadly, they (and additional new methods) could benefit from adding features to explore haplotype blocks, as we define them. Understanding and applying the concept of the haplotype block will be essential to fully exploit long and linked-read sequencing technologies.","lang":"eng"}],"status":"public"},{"status":"public","abstract":[{"text":"Small GTPases play essential roles in the organization of eukaryotic cells. In recent years, it has become clear that their intracellular functions result from intricate biochemical networks of the GTPase and their regulators that dynamically bind to a membrane surface. Due to the inherent complexities of their interactions, however, revealing the underlying mechanisms of action is often difficult to achieve from in vivo studies. This review summarizes in vitro reconstitution approaches developed to obtain a better mechanistic understanding of how small GTPase activities are regulated in space and time.","lang":"eng"}],"day":"01","has_accepted_license":"1","keyword":["Cell Biology","Genetics","Molecular Biology","Biochemistry","Structural Biology","Biophysics"],"intvolume":"       597","citation":{"apa":"Loose, M., Auer, A., Brognara, G., Budiman, H. R., Kowalski, L. M., &#38; Matijevic, I. (2023). In vitro reconstitution of small GTPase regulation. <i>FEBS Letters</i>. Wiley. <a href=\"https://doi.org/10.1002/1873-3468.14540\">https://doi.org/10.1002/1873-3468.14540</a>","ista":"Loose M, Auer A, Brognara G, Budiman HR, Kowalski LM, Matijevic I. 2023. In vitro reconstitution of small GTPase regulation. FEBS Letters. 597(6), 762–777.","chicago":"Loose, Martin, Albert Auer, Gabriel Brognara, Hanifatul R Budiman, Lukasz M Kowalski, and Ivana Matijevic. “In Vitro Reconstitution of Small GTPase Regulation.” <i>FEBS Letters</i>. Wiley, 2023. <a href=\"https://doi.org/10.1002/1873-3468.14540\">https://doi.org/10.1002/1873-3468.14540</a>.","mla":"Loose, Martin, et al. “In Vitro Reconstitution of Small GTPase Regulation.” <i>FEBS Letters</i>, vol. 597, no. 6, Wiley, 2023, pp. 762–77, doi:<a href=\"https://doi.org/10.1002/1873-3468.14540\">10.1002/1873-3468.14540</a>.","ieee":"M. Loose, A. Auer, G. Brognara, H. R. Budiman, L. M. Kowalski, and I. Matijevic, “In vitro reconstitution of small GTPase regulation,” <i>FEBS Letters</i>, vol. 597, no. 6. Wiley, pp. 762–777, 2023.","short":"M. Loose, A. Auer, G. Brognara, H.R. Budiman, L.M. Kowalski, I. Matijevic, FEBS Letters 597 (2023) 762–777.","ama":"Loose M, Auer A, Brognara G, Budiman HR, Kowalski LM, Matijevic I. In vitro reconstitution of small GTPase regulation. <i>FEBS Letters</i>. 2023;597(6):762-777. doi:<a href=\"https://doi.org/10.1002/1873-3468.14540\">10.1002/1873-3468.14540</a>"},"_id":"12163","month":"03","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication_status":"published","oa":1,"title":"In vitro reconstitution of small GTPase regulation","article_type":"review","department":[{"_id":"MaLo"}],"acknowledgement":"The authors acknowledge support from IST Austria and helpful comments from the anonymous reviewers that helped to improve this manuscript. We apologize to the authors of primary literature and outstanding research not cited here due to space restraints.","year":"2023","date_created":"2023-01-12T12:09:58Z","quality_controlled":"1","page":"762-777","date_updated":"2023-08-16T08:32:29Z","isi":1,"file":[{"content_type":"application/pdf","file_id":"14063","date_created":"2023-08-16T08:31:04Z","success":1,"access_level":"open_access","date_updated":"2023-08-16T08:31:04Z","file_name":"2023_FEBSLetters_Loose.pdf","file_size":3148143,"creator":"dernst","relation":"main_file","checksum":"7492244d3f9c5faa1347ef03f6e5bc84"}],"volume":597,"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","image":"/images/cc_by_nc_nd.png","short":"CC BY-NC-ND (4.0)"},"article_processing_charge":"Yes (via OA deal)","publication_identifier":{"issn":["0014-5793"],"eissn":["1873-3468"]},"pmid":1,"scopus_import":"1","doi":"10.1002/1873-3468.14540","publisher":"Wiley","language":[{"iso":"eng"}],"type":"journal_article","file_date_updated":"2023-08-16T08:31:04Z","oa_version":"Published Version","external_id":{"isi":["000891573000001"],"pmid":["36448231"]},"date_published":"2023-03-01T00:00:00Z","issue":"6","publication":"FEBS Letters","author":[{"full_name":"Loose, Martin","first_name":"Martin","last_name":"Loose","id":"462D4284-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-7309-9724"},{"orcid":"0000-0002-3580-2906","id":"3018E8C2-F248-11E8-B48F-1D18A9856A87","last_name":"Auer","first_name":"Albert","full_name":"Auer, Albert"},{"id":"D96FFDA0-A884-11E9-9968-DC26E6697425","last_name":"Brognara","first_name":"Gabriel","full_name":"Brognara, Gabriel"},{"full_name":"Budiman, Hanifatul R","first_name":"Hanifatul R","last_name":"Budiman","id":"55380f95-15b2-11ec-abd3-aff8e230696b"},{"first_name":"Lukasz M","full_name":"Kowalski, Lukasz M","last_name":"Kowalski","id":"e3a512e2-4bbe-11eb-a68a-e3857a7844c2"},{"last_name":"Matijevic","first_name":"Ivana","full_name":"Matijevic, Ivana","id":"83c17ce3-15b2-11ec-abd3-f486545870bd"}],"ddc":["570"]},{"author":[{"last_name":"Mrnjavac","full_name":"Mrnjavac, Andrea","first_name":"Andrea","id":"353FAC84-AE61-11E9-8BFC-00D3E5697425"},{"first_name":"Kseniia","full_name":"Khudiakova, Kseniia","last_name":"Khudiakova","id":"4E6DC800-AE37-11E9-AC72-31CAE5697425","orcid":"0000-0002-6246-1465"},{"full_name":"Barton, Nicholas H","first_name":"Nicholas H","last_name":"Barton","orcid":"0000-0002-8548-5240","id":"4880FE40-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-4579-8306","id":"49E1C5C6-F248-11E8-B48F-1D18A9856A87","full_name":"Vicoso, Beatriz","first_name":"Beatriz","last_name":"Vicoso"}],"ddc":["570"],"publication":"Evolution Letters","issue":"1","date_published":"2023-02-01T00:00:00Z","oa_version":"Published Version","external_id":{"pmid":["37065438"],"isi":["001021692200001"]},"type":"journal_article","file_date_updated":"2023-08-16T11:43:33Z","language":[{"iso":"eng"}],"publisher":"Oxford University Press","doi":"10.1093/evlett/qrac004","pmid":1,"scopus_import":"1","publication_identifier":{"issn":["2056-3744"]},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"article_processing_charge":"Yes (via OA deal)","isi":1,"file":[{"relation":"main_file","checksum":"a240a041cb9b9b7c8ba93a4706674a3f","file_size":2592189,"creator":"dernst","file_name":"2023_EvLetters_Mrnjavac.pdf","date_created":"2023-08-16T11:43:33Z","content_type":"application/pdf","file_id":"14068","access_level":"open_access","date_updated":"2023-08-16T11:43:33Z","success":1}],"volume":7,"project":[{"grant_number":"716117","name":"Optimal Transport and Stochastic Dynamics","_id":"256E75B8-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"call_identifier":"H2020","name":"Prevalence and Influence of Sexual Antagonism on Genome Evolution","grant_number":"715257","_id":"250BDE62-B435-11E9-9278-68D0E5697425"}],"date_updated":"2023-08-16T11:44:32Z","date_created":"2023-02-06T13:59:12Z","year":"2023","quality_controlled":"1","department":[{"_id":"GradSch"},{"_id":"BeVi"}],"acknowledgement":"We thank the Vicoso and Barton groups and ISTA Scientific Computing Unit. We also thank two anonymous reviewers for their valuable comments. This work was supported by the European Research Council under the European Union’s Horizon 2020 research and innovation program (grant agreements no. 715257 and no. 716117).","article_type":"original","publication_status":"published","title":"Slower-X: Reduced efficiency of selection in the early stages of X chromosome evolution","oa":1,"month":"02","_id":"12521","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","intvolume":"         7","citation":{"ama":"Mrnjavac A, Khudiakova K, Barton NH, Vicoso B. Slower-X: Reduced efficiency of selection in the early stages of X chromosome evolution. <i>Evolution Letters</i>. 2023;7(1). doi:<a href=\"https://doi.org/10.1093/evlett/qrac004\">10.1093/evlett/qrac004</a>","short":"A. Mrnjavac, K. Khudiakova, N.H. Barton, B. Vicoso, Evolution Letters 7 (2023).","ieee":"A. Mrnjavac, K. Khudiakova, N. H. Barton, and B. Vicoso, “Slower-X: Reduced efficiency of selection in the early stages of X chromosome evolution,” <i>Evolution Letters</i>, vol. 7, no. 1. Oxford University Press, 2023.","mla":"Mrnjavac, Andrea, et al. “Slower-X: Reduced Efficiency of Selection in the Early Stages of X Chromosome Evolution.” <i>Evolution Letters</i>, vol. 7, no. 1, qrac004, Oxford University Press, 2023, doi:<a href=\"https://doi.org/10.1093/evlett/qrac004\">10.1093/evlett/qrac004</a>.","chicago":"Mrnjavac, Andrea, Kseniia Khudiakova, Nicholas H Barton, and Beatriz Vicoso. “Slower-X: Reduced Efficiency of Selection in the Early Stages of X Chromosome Evolution.” <i>Evolution Letters</i>. Oxford University Press, 2023. <a href=\"https://doi.org/10.1093/evlett/qrac004\">https://doi.org/10.1093/evlett/qrac004</a>.","ista":"Mrnjavac A, Khudiakova K, Barton NH, Vicoso B. 2023. Slower-X: Reduced efficiency of selection in the early stages of X chromosome evolution. Evolution Letters. 7(1), qrac004.","apa":"Mrnjavac, A., Khudiakova, K., Barton, N. H., &#38; Vicoso, B. (2023). Slower-X: Reduced efficiency of selection in the early stages of X chromosome evolution. <i>Evolution Letters</i>. Oxford University Press. <a href=\"https://doi.org/10.1093/evlett/qrac004\">https://doi.org/10.1093/evlett/qrac004</a>"},"keyword":["Genetics","Ecology","Evolution","Behavior and Systematics"],"has_accepted_license":"1","day":"01","abstract":[{"lang":"eng","text":"Differentiated X chromosomes are expected to have higher rates of adaptive divergence than autosomes, if new beneficial mutations are recessive (the “faster-X effect”), largely because these mutations are immediately exposed to selection in males. The evolution of X chromosomes after they stop recombining in males, but before they become hemizygous, has not been well explored theoretically. We use the diffusion approximation to infer substitution rates of beneficial and deleterious mutations under such a scenario. Our results show that selection is less efficient on diploid X loci than on autosomal and hemizygous X loci under a wide range of parameters. This “slower-X” effect is stronger for genes affecting primarily (or only) male fitness, and for sexually antagonistic genes. These unusual dynamics suggest that some of the peculiar features of X chromosomes, such as the differential accumulation of genes with sex-specific functions, may start arising earlier than previously appreciated."}],"status":"public","article_number":"qrac004","ec_funded":1},{"acknowledgement":"We thank A. Freeman and V. Voronin for technical assistance, S. Deixler, A. Stichelberger, M. Schunn, and the Preclinical Facility for managing our animal colony. We thank L. Andersen and J. Sonntag, who were involved in generating the MADM lines. We thank the ISTA LSF Mass Spectrometry Core Facility for assistance with the proteomic analysis, as well as the ISTA electron microscopy and Imaging and Optics facility for technical support. Metabolomics LC-MS/MS analysis was performed by the Metabolomics Facility at Vienna BioCenter Core Facilities (VBCF). We acknowledge the support of the EMBL Metabolomics Core Facility (MCF) for lipidomics and intracellular metabolomics mass spectrometry data acquisition and analysis. RNA sequencing was performed by the Next Generation Sequencing Facility at VBCF. Schematics were generated using Biorender.com. This work was supported by the Austrian Science Fund (FWF, DK W1232-B24) and by the European Union’s Horizon 2020 research and innovation program (ERC) grant 725780 (LinPro) to S.H. and 715508 (REVERSEAUTISM) to G.N.","department":[{"_id":"SiHi"},{"_id":"GaNo"}],"month":"04","_id":"12802","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publication_status":"published","oa":1,"related_material":{"record":[{"id":"13107","relation":"dissertation_contains","status":"public"}],"link":[{"url":"https://ista.ac.at/en/news/feed-them-or-lose-them/","description":"News on ISTA Website","relation":"press_release"}]},"title":"Large neutral amino acid levels tune perinatal neuronal excitability and survival","article_type":"original","day":"27","has_accepted_license":"1","keyword":["General Biochemistry","Genetics and Molecular Biology"],"intvolume":"       186","citation":{"short":"L. Knaus, B. Basilico, D. Malzl, M. Gerykova Bujalkova, M. Smogavec, L.A. Schwarz, S. Gorkiewicz, N. Amberg, F. Pauler, C. Knittl-Frank, M. Tassinari, N. Maulide, T. Rülicke, J. Menche, S. Hippenmeyer, G. Novarino, Cell 186 (2023) 1950–1967.e25.","ama":"Knaus L, Basilico B, Malzl D, et al. Large neutral amino acid levels tune perinatal neuronal excitability and survival. <i>Cell</i>. 2023;186(9):1950-1967.e25. doi:<a href=\"https://doi.org/10.1016/j.cell.2023.02.037\">10.1016/j.cell.2023.02.037</a>","ista":"Knaus L, Basilico B, Malzl D, Gerykova Bujalkova M, Smogavec M, Schwarz LA, Gorkiewicz S, Amberg N, Pauler F, Knittl-Frank C, Tassinari M, Maulide N, Rülicke T, Menche J, Hippenmeyer S, Novarino G. 2023. Large neutral amino acid levels tune perinatal neuronal excitability and survival. Cell. 186(9), 1950–1967.e25.","chicago":"Knaus, Lisa, Bernadette Basilico, Daniel Malzl, Maria Gerykova Bujalkova, Mateja Smogavec, Lena A. Schwarz, Sarah Gorkiewicz, et al. “Large Neutral Amino Acid Levels Tune Perinatal Neuronal Excitability and Survival.” <i>Cell</i>. Elsevier, 2023. <a href=\"https://doi.org/10.1016/j.cell.2023.02.037\">https://doi.org/10.1016/j.cell.2023.02.037</a>.","apa":"Knaus, L., Basilico, B., Malzl, D., Gerykova Bujalkova, M., Smogavec, M., Schwarz, L. A., … Novarino, G. (2023). Large neutral amino acid levels tune perinatal neuronal excitability and survival. <i>Cell</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cell.2023.02.037\">https://doi.org/10.1016/j.cell.2023.02.037</a>","mla":"Knaus, Lisa, et al. “Large Neutral Amino Acid Levels Tune Perinatal Neuronal Excitability and Survival.” <i>Cell</i>, vol. 186, no. 9, Elsevier, 2023, p. 1950–1967.e25, doi:<a href=\"https://doi.org/10.1016/j.cell.2023.02.037\">10.1016/j.cell.2023.02.037</a>.","ieee":"L. Knaus <i>et al.</i>, “Large neutral amino acid levels tune perinatal neuronal excitability and survival,” <i>Cell</i>, vol. 186, no. 9. Elsevier, p. 1950–1967.e25, 2023."},"ec_funded":1,"status":"public","abstract":[{"text":"Little is known about the critical metabolic changes that neural cells have to undergo during development and how temporary shifts in this program can influence brain circuitries and behavior. Inspired by the discovery that mutations in SLC7A5, a transporter of metabolically essential large neutral amino acids (LNAAs), lead to autism, we employed metabolomic profiling to study the metabolic states of the cerebral cortex across different developmental stages. We found that the forebrain undergoes significant metabolic remodeling throughout development, with certain groups of metabolites showing stage-specific changes, but what are the consequences of perturbing this metabolic program? By manipulating Slc7a5 expression in neural cells, we found that the metabolism of LNAAs and lipids are interconnected in the cortex. Deletion of Slc7a5 in neurons affects the postnatal metabolic state, leading to a shift in lipid metabolism. Additionally, it causes stage- and cell-type-specific alterations in neuronal activity patterns, resulting in a long-term circuit dysfunction.","lang":"eng"}],"external_id":{"isi":["000991468700001"]},"oa_version":"Published Version","date_published":"2023-04-27T00:00:00Z","publication":"Cell","issue":"9","author":[{"id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","last_name":"Knaus","first_name":"Lisa","full_name":"Knaus, Lisa"},{"id":"36035796-5ACA-11E9-A75E-7AF2E5697425","orcid":"0000-0003-1843-3173","first_name":"Bernadette","full_name":"Basilico, Bernadette","last_name":"Basilico"},{"last_name":"Malzl","full_name":"Malzl, Daniel","first_name":"Daniel"},{"first_name":"Maria","full_name":"Gerykova Bujalkova, Maria","last_name":"Gerykova Bujalkova"},{"last_name":"Smogavec","first_name":"Mateja","full_name":"Smogavec, Mateja"},{"last_name":"Schwarz","first_name":"Lena A.","full_name":"Schwarz, Lena A."},{"last_name":"Gorkiewicz","first_name":"Sarah","full_name":"Gorkiewicz, Sarah","id":"f141a35d-15a9-11ec-9fb2-fef6becc7b6f"},{"id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3183-8207","full_name":"Amberg, Nicole","first_name":"Nicole","last_name":"Amberg"},{"full_name":"Pauler, Florian","first_name":"Florian","last_name":"Pauler","orcid":"0000-0002-7462-0048","id":"48EA0138-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Knittl-Frank","first_name":"Christian","full_name":"Knittl-Frank, Christian"},{"id":"7af593f1-d44a-11ed-bf94-a3646a6bb35e","first_name":"Marianna","full_name":"Tassinari, Marianna","last_name":"Tassinari"},{"last_name":"Maulide","first_name":"Nuno","full_name":"Maulide, Nuno"},{"full_name":"Rülicke, Thomas","first_name":"Thomas","last_name":"Rülicke"},{"last_name":"Menche","full_name":"Menche, Jörg","first_name":"Jörg"},{"last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","first_name":"Simon","orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia","full_name":"Novarino, Gaia"}],"ddc":["570"],"doi":"10.1016/j.cell.2023.02.037","publisher":"Elsevier","language":[{"iso":"eng"}],"type":"journal_article","file_date_updated":"2023-05-02T09:26:21Z","article_processing_charge":"Yes (via OA deal)","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"publication_identifier":{"issn":["0092-8674"]},"scopus_import":"1","year":"2023","date_created":"2023-04-05T08:15:40Z","quality_controlled":"1","page":"1950-1967.e25","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"EM-Fac"},{"_id":"Bio"},{"_id":"LifeSc"}],"project":[{"_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24","name":"Molecular Drug Targets","call_identifier":"FWF"},{"call_identifier":"H2020","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780","_id":"260018B0-B435-11E9-9278-68D0E5697425"},{"name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","grant_number":"715508","_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}],"date_updated":"2024-02-07T08:03:32Z","isi":1,"file":[{"file_size":15712841,"creator":"dernst","relation":"main_file","checksum":"47e94fbe19e86505b429cb7a5b503ce6","date_created":"2023-05-02T09:26:21Z","content_type":"application/pdf","file_id":"12889","access_level":"open_access","success":1,"date_updated":"2023-05-02T09:26:21Z","file_name":"2023_Cell_Knaus.pdf"}],"volume":186},{"citation":{"short":"N.H. Barton, (2023).","ama":"Barton NH. The infinitesimal model with dominance. 2023. doi:<a href=\"https://doi.org/10.15479/AT:ISTA:12949\">10.15479/AT:ISTA:12949</a>","ista":"Barton NH. 2023. The infinitesimal model with dominance, Institute of Science and Technology Austria, <a href=\"https://doi.org/10.15479/AT:ISTA:12949\">10.15479/AT:ISTA:12949</a>.","apa":"Barton, N. H. (2023). The infinitesimal model with dominance. Institute of Science and Technology Austria. <a href=\"https://doi.org/10.15479/AT:ISTA:12949\">https://doi.org/10.15479/AT:ISTA:12949</a>","chicago":"Barton, Nicholas H. “The Infinitesimal Model with Dominance.” Institute of Science and Technology Austria, 2023. <a href=\"https://doi.org/10.15479/AT:ISTA:12949\">https://doi.org/10.15479/AT:ISTA:12949</a>.","mla":"Barton, Nicholas H. <i>The Infinitesimal Model with Dominance</i>. Institute of Science and Technology Austria, 2023, doi:<a href=\"https://doi.org/10.15479/AT:ISTA:12949\">10.15479/AT:ISTA:12949</a>.","ieee":"N. H. Barton, “The infinitesimal model with dominance.” Institute of Science and Technology Austria, 2023."},"keyword":["Quantitative genetics","infinitesimal model"],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"article_processing_charge":"No","has_accepted_license":"1","day":"13","abstract":[{"text":"The classical infinitesimal model is a simple and robust model for the inheritance of quantitative traits. In this model, a quantitative trait is expressed as the sum of a genetic and a non-genetic (environmental) component and the genetic component of offspring traits within a family follows a normal distribution around the average of the parents’ trait values, and has a variance that is independent of the trait values of the parents. Although the trait distribution across the whole population can be far from normal, the trait distributions within families are normally distributed with a variance-covariance matrix that is determined entirely by that in  the ancestral population and the probabilities of identity determined by the pedigree. Moreover, conditioning on some of the trait values within the pedigree has predictable effects on the mean and variance within and between families. In previous work, Barton et al. (2017), we showed that when trait values are determined by the sum of a large number of Mendelian factors, each  of small effect, one can justify the infinitesimal model as limit of Mendelian inheritance. It was also shown that under some forms of epistasis, trait values within a family are still normally distributed.","lang":"eng"}],"contributor":[{"contributor_type":"researcher","first_name":"Amandine","last_name":"Veber"},{"first_name":"Alison","last_name":"Etheridge","contributor_type":"researcher"}],"file":[{"checksum":"b0ce7d4b1ee7e7265430ceed36fc3336","relation":"main_file","creator":"nbarton","file_size":13662,"file_name":"Neutral identities 16th Jan","access_level":"open_access","date_updated":"2023-05-13T09:36:33Z","success":1,"file_id":"12950","content_type":"application/octet-stream","date_created":"2023-05-13T09:36:33Z"},{"relation":"main_file","checksum":"ad5035ad4f7d3b150a252c79884f6a83","file_size":181619928,"creator":"nbarton","file_name":"p, zA, zD, N=30 neutral III","content_type":"application/octet-stream","file_id":"12951","date_created":"2023-05-13T09:38:17Z","date_updated":"2023-05-13T09:38:17Z","access_level":"open_access","success":1},{"creator":"nbarton","file_size":605902074,"checksum":"62182a1de796256edd6f4223704312ef","relation":"main_file","access_level":"open_access","success":1,"date_updated":"2023-05-13T09:41:59Z","content_type":"application/octet-stream","date_created":"2023-05-13T09:41:59Z","file_id":"12952","file_name":"p, zA, zD, N=30 neutral IV"},{"creator":"nbarton","file_size":1018238746,"checksum":"af775dda5c4f6859cb1e5a81ec40a667","relation":"main_file","success":1,"access_level":"open_access","date_updated":"2023-05-13T09:46:52Z","content_type":"application/octet-stream","date_created":"2023-05-13T09:46:52Z","file_id":"12953","file_name":"p, zA, zD, N=30 selected k=5"},{"file_name":"Pairwise F N=30 neutral II","content_type":"application/octet-stream","date_created":"2023-05-13T09:42:05Z","file_id":"12954","access_level":"open_access","success":1,"date_updated":"2023-05-13T09:42:05Z","relation":"main_file","checksum":"af26f3394c387d3ada14b434cd68b1e5","file_size":3197160,"creator":"nbarton"},{"file_size":55492,"creator":"nbarton","relation":"main_file","checksum":"d5da7dc0e7282dd48222e26d12e34220","content_type":"application/octet-stream","date_created":"2023-05-13T09:42:06Z","file_id":"12955","date_updated":"2023-05-13T09:42:06Z","access_level":"open_access","success":1,"file_name":"Pedigrees N=30 neutral II"},{"relation":"main_file","checksum":"00f386d80677590e29f6235d49cba58d","file_size":474003467,"creator":"nbarton","file_name":"selected reps N=30 selected k=1,2 300 reps III","content_type":"application/octet-stream","date_created":"2023-05-13T09:46:06Z","file_id":"12956","success":1,"access_level":"open_access","date_updated":"2023-05-13T09:46:06Z"},{"checksum":"658cef3eaea6136a4d24da4f074191d7","relation":"main_file","creator":"nbarton","file_size":121209,"file_name":"Algorithm for caclulating identities.nb","success":1,"access_level":"open_access","date_updated":"2023-05-13T09:46:08Z","content_type":"application/octet-stream","date_created":"2023-05-13T09:46:08Z","file_id":"12957"},{"content_type":"application/octet-stream","file_id":"12958","date_created":"2023-05-13T09:46:08Z","date_updated":"2023-05-13T09:46:08Z","access_level":"open_access","success":1,"file_name":"Infinitesimal with dominance.nb","file_size":1803898,"creator":"nbarton","relation":"main_file","checksum":"db9b6dddd7a596d974e25f5e78f5c45c"},{"file_size":990,"creator":"nbarton","relation":"main_file","checksum":"91f80a9fb58cae8eef2d8bf59fe30189","date_created":"2023-05-16T04:09:08Z","content_type":"text/plain","file_id":"12967","access_level":"open_access","success":1,"date_updated":"2023-05-16T04:09:08Z","file_name":"ReadMe.txt"}],"status":"public","date_updated":"2025-05-28T11:57:00Z","project":[{"_id":"bd6958e0-d553-11ed-ba76-86eba6a76c00","name":"Understanding the evolution of continuous genomes","grant_number":"101055327"}],"date_created":"2023-05-13T09:49:09Z","year":"2023","ddc":["576"],"author":[{"orcid":"0000-0002-8548-5240","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","full_name":"Barton, Nicholas H","first_name":"Nicholas H","last_name":"Barton"}],"date_published":"2023-05-13T00:00:00Z","department":[{"_id":"NiBa"}],"oa_version":"Published Version","file_date_updated":"2023-05-16T04:09:08Z","type":"research_data","related_material":{"record":[{"id":"14452","status":"public","relation":"used_in_publication"}]},"title":"The infinitesimal model with dominance","oa":1,"publisher":"Institute of Science and Technology Austria","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"12949","month":"05","doi":"10.15479/AT:ISTA:12949"},{"day":"01","keyword":["Genetics","Ecology","Evolution","Behavior and Systematics"],"citation":{"ista":"Stankowski S, Chase MA, McIntosh H, Streisfeld MA. 2023. Integrating top‐down and bottom‐up approaches to understand the genetic architecture of speciation across a monkeyflower hybrid zone. Molecular Ecology. 32(8), 2041–2054.","apa":"Stankowski, S., Chase, M. A., McIntosh, H., &#38; Streisfeld, M. A. (2023). Integrating top‐down and bottom‐up approaches to understand the genetic architecture of speciation across a monkeyflower hybrid zone. <i>Molecular Ecology</i>. Wiley. <a href=\"https://doi.org/10.1111/mec.16849\">https://doi.org/10.1111/mec.16849</a>","chicago":"Stankowski, Sean, Madeline A. Chase, Hanna McIntosh, and Matthew A. Streisfeld. “Integrating Top‐down and Bottom‐up Approaches to Understand the Genetic Architecture of Speciation across a Monkeyflower Hybrid Zone.” <i>Molecular Ecology</i>. Wiley, 2023. <a href=\"https://doi.org/10.1111/mec.16849\">https://doi.org/10.1111/mec.16849</a>.","ieee":"S. Stankowski, M. A. Chase, H. McIntosh, and M. A. Streisfeld, “Integrating top‐down and bottom‐up approaches to understand the genetic architecture of speciation across a monkeyflower hybrid zone,” <i>Molecular Ecology</i>, vol. 32, no. 8. Wiley, pp. 2041–2054, 2023.","mla":"Stankowski, Sean, et al. “Integrating Top‐down and Bottom‐up Approaches to Understand the Genetic Architecture of Speciation across a Monkeyflower Hybrid Zone.” <i>Molecular Ecology</i>, vol. 32, no. 8, Wiley, 2023, pp. 2041–54, doi:<a href=\"https://doi.org/10.1111/mec.16849\">10.1111/mec.16849</a>.","short":"S. Stankowski, M.A. Chase, H. McIntosh, M.A. Streisfeld, Molecular Ecology 32 (2023) 2041–2054.","ama":"Stankowski S, Chase MA, McIntosh H, Streisfeld MA. Integrating top‐down and bottom‐up approaches to understand the genetic architecture of speciation across a monkeyflower hybrid zone. <i>Molecular Ecology</i>. 2023;32(8):2041-2054. doi:<a href=\"https://doi.org/10.1111/mec.16849\">10.1111/mec.16849</a>"},"intvolume":"        32","status":"public","abstract":[{"text":"Understanding the phenotypic and genetic architecture of reproductive isolation is a long‐standing goal of speciation research. In several systems, large‐effect loci contributing to barrier phenotypes have been characterized, but such causal connections are rarely known for more complex genetic architectures. In this study, we combine “top‐down” and “bottom‐up” approaches with demographic modelling toward an integrated understanding of speciation across a monkeyflower hybrid zone. Previous work suggests that pollinator visitation acts as a primary barrier to gene flow between two divergent red‐ and yellow‐flowered ecotypes of<jats:italic>Mimulus aurantiacus</jats:italic>. Several candidate isolating traits and anonymous single nucleotide polymorphism loci under divergent selection have been identified, but their genomic positions remain unknown. Here, we report findings from demographic analyses that indicate this hybrid zone formed by secondary contact, but that subsequent gene flow was restricted by widespread barrier loci across the genome. Using a novel, geographic cline‐based genome scan, we demonstrate that candidate barrier loci are broadly distributed across the genome, rather than mapping to one or a few “islands of speciation.” Quantitative trait locus (QTL) mapping reveals that most floral traits are highly polygenic, with little evidence that QTL colocalize, indicating that most traits are genetically independent. Finally, we find little evidence that QTL and candidate barrier loci overlap, suggesting that some loci contribute to other forms of reproductive isolation. Our findings highlight the challenges of understanding the genetic architecture of reproductive isolation and reveal that barriers to gene flow other than pollinator isolation may play an important role in this system.","lang":"eng"}],"acknowledgement":"We thank Julian Catchen for making modifications to Stacks to aid this project. Peter L. Ralph, Thomas Nelson, Roger K. Butlin, Anja M. Westram and Nicholas H. Barton provided advice, stimulating discussion and critical feedback. The project was supported by National Science Foundation grant DEB-1258199.","department":[{"_id":"NiBa"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"04","_id":"14787","title":"Integrating top‐down and bottom‐up approaches to understand the genetic architecture of speciation across a monkeyflower hybrid zone","oa":1,"publication_status":"published","article_type":"original","article_processing_charge":"No","publication_identifier":{"eissn":["1365-294X"],"issn":["0962-1083"]},"main_file_link":[{"url":"https://doi.org/10.1101/2022.01.28.478139","open_access":"1"}],"pmid":1,"page":"2041-2054","quality_controlled":"1","date_created":"2024-01-10T10:44:45Z","year":"2023","date_updated":"2024-01-16T10:10:00Z","volume":32,"isi":1,"external_id":{"pmid":["36651268"],"isi":["000919244600001"]},"oa_version":"Preprint","date_published":"2023-04-01T00:00:00Z","issue":"8","publication":"Molecular Ecology","author":[{"id":"43161670-5719-11EA-8025-FABC3DDC885E","last_name":"Stankowski","full_name":"Stankowski, Sean","first_name":"Sean"},{"first_name":"Madeline A.","full_name":"Chase, Madeline A.","last_name":"Chase"},{"last_name":"McIntosh","full_name":"McIntosh, Hanna","first_name":"Hanna"},{"last_name":"Streisfeld","full_name":"Streisfeld, Matthew A.","first_name":"Matthew A."}],"doi":"10.1111/mec.16849","publisher":"Wiley","language":[{"iso":"eng"}],"type":"journal_article"},{"day":"14","keyword":["General Physics and Astronomy","General Biochemistry","Genetics and Molecular Biology","General Chemistry","Multidisciplinary"],"intvolume":"        14","citation":{"short":"J. Hales, U. Bajpai, T. Liu, D.R. Baykusheva, M. Li, M. Mitrano, Y. Wang, Nature Communications 14 (2023).","ama":"Hales J, Bajpai U, Liu T, et al. Witnessing light-driven entanglement using time-resolved resonant inelastic X-ray scattering. <i>Nature Communications</i>. 2023;14. doi:<a href=\"https://doi.org/10.1038/s41467-023-38540-3\">10.1038/s41467-023-38540-3</a>","ista":"Hales J, Bajpai U, Liu T, Baykusheva DR, Li M, Mitrano M, Wang Y. 2023. Witnessing light-driven entanglement using time-resolved resonant inelastic X-ray scattering. Nature Communications. 14, 3512.","apa":"Hales, J., Bajpai, U., Liu, T., Baykusheva, D. R., Li, M., Mitrano, M., &#38; Wang, Y. (2023). Witnessing light-driven entanglement using time-resolved resonant inelastic X-ray scattering. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-023-38540-3\">https://doi.org/10.1038/s41467-023-38540-3</a>","chicago":"Hales, Jordyn, Utkarsh Bajpai, Tongtong Liu, Denitsa Rangelova Baykusheva, Mingda Li, Matteo Mitrano, and Yao Wang. “Witnessing Light-Driven Entanglement Using Time-Resolved Resonant Inelastic X-Ray Scattering.” <i>Nature Communications</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1038/s41467-023-38540-3\">https://doi.org/10.1038/s41467-023-38540-3</a>.","mla":"Hales, Jordyn, et al. “Witnessing Light-Driven Entanglement Using Time-Resolved Resonant Inelastic X-Ray Scattering.” <i>Nature Communications</i>, vol. 14, 3512, Springer Nature, 2023, doi:<a href=\"https://doi.org/10.1038/s41467-023-38540-3\">10.1038/s41467-023-38540-3</a>.","ieee":"J. Hales <i>et al.</i>, “Witnessing light-driven entanglement using time-resolved resonant inelastic X-ray scattering,” <i>Nature Communications</i>, vol. 14. Springer Nature, 2023."},"article_number":"3512","status":"public","abstract":[{"lang":"eng","text":"Characterizing and controlling entanglement in quantum materials is crucial for the development of next-generation quantum technologies. However, defining a quantifiable figure of merit for entanglement in macroscopic solids is theoretically and experimentally challenging. At equilibrium the presence of entanglement can be diagnosed by extracting entanglement witnesses from spectroscopic observables and a nonequilibrium extension of this method could lead to the discovery of novel dynamical phenomena. Here, we propose a systematic approach to quantify the time-dependent quantum Fisher information and entanglement depth of transient states of quantum materials with time-resolved resonant inelastic x-ray scattering. Using a quarter-filled extended Hubbard model as an example, we benchmark the efficiency of this approach and predict a light-enhanced many-body entanglement due to the proximity to a phase boundary. Our work sets the stage for experimentally witnessing and controlling entanglement in light-driven quantum materials via ultrafast spectroscopic measurements."}],"extern":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"06","_id":"13989","title":"Witnessing light-driven entanglement using time-resolved resonant inelastic X-ray scattering","oa":1,"publication_status":"published","article_type":"original","article_processing_charge":"No","publication_identifier":{"eissn":["2041-1723"]},"scopus_import":"1","main_file_link":[{"url":"https://doi.org/10.1038/s41467-023-38540-3","open_access":"1"}],"pmid":1,"quality_controlled":"1","date_created":"2023-08-09T13:06:59Z","year":"2023","date_updated":"2023-08-22T06:50:04Z","volume":14,"external_id":{"pmid":["37316515"],"arxiv":["2209.02283"]},"oa_version":"Published Version","date_published":"2023-06-14T00:00:00Z","publication":"Nature Communications","author":[{"last_name":"Hales","full_name":"Hales, Jordyn","first_name":"Jordyn"},{"first_name":"Utkarsh","full_name":"Bajpai, Utkarsh","last_name":"Bajpai"},{"full_name":"Liu, Tongtong","first_name":"Tongtong","last_name":"Liu"},{"id":"71b4d059-2a03-11ee-914d-dfa3beed6530","first_name":"Denitsa Rangelova","full_name":"Baykusheva, Denitsa Rangelova","last_name":"Baykusheva"},{"last_name":"Li","first_name":"Mingda","full_name":"Li, Mingda"},{"last_name":"Mitrano","first_name":"Matteo","full_name":"Mitrano, Matteo"},{"full_name":"Wang, Yao","first_name":"Yao","last_name":"Wang"}],"doi":"10.1038/s41467-023-38540-3","publisher":"Springer Nature","arxiv":1,"language":[{"iso":"eng"}],"type":"journal_article"},{"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"14077","month":"08","title":"Sex-specific estimation of cis and trans regulation of gene expression in heads and gonads of Drosophila melanogaster","related_material":{"record":[{"relation":"research_data","status":"public","id":"12933"},{"relation":"dissertation_contains","status":"public","id":"14058"}]},"oa":1,"publication_status":"published","article_type":"original","acknowledgement":"We thank members of the Vicoso Group for comments on the manuscript, the Scientific Computing Unit at ISTA for technical support, and 2 anonymous reviewers for useful feedback. GP is the recipient of a DOC Fellowship of the Austrian Academy of Sciences at the Institute of Science and Technology Austria (DOC 25817) and received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie Grant (agreement no. 665385).","department":[{"_id":"BeVi"},{"_id":"NiBa"},{"_id":"GradSch"}],"ec_funded":1,"status":"public","abstract":[{"lang":"eng","text":"The regulatory architecture of gene expression is known to differ substantially between sexes in Drosophila, but most studies performed\r\nso far used whole-body data and only single crosses, which may have limited their scope to detect patterns that are robust across tissues\r\nand biological replicates. Here, we use allele-specific gene expression of parental and reciprocal hybrid crosses between 6 Drosophila\r\nmelanogaster inbred lines to quantify cis- and trans-regulatory variation in heads and gonads of both sexes separately across 3 replicate\r\ncrosses. Our results suggest that female and male heads, as well as ovaries, have a similar regulatory architecture. On the other hand,\r\ntestes display more and substantially different cis-regulatory effects, suggesting that sex differences in the regulatory architecture that\r\nhave been previously observed may largely derive from testis-specific effects. We also examine the difference in cis-regulatory variation\r\nof genes across different levels of sex bias in gonads and heads. Consistent with the idea that intersex correlations constrain expression\r\nand can lead to sexual antagonism, we find more cis variation in unbiased and moderately biased genes in heads. In ovaries, reduced cis\r\nvariation is observed for male-biased genes, suggesting that cis variants acting on these genes in males do not lead to changes in ovary\r\nexpression. Finally, we examine the dominance patterns of gene expression and find that sex- and tissue-specific patterns of inheritance\r\nas well as trans-regulatory variation are highly variable across biological crosses, although these were performed in highly controlled\r\nexperimental conditions. This highlights the importance of using various genetic backgrounds to infer generalizable patterns."}],"day":"01","has_accepted_license":"1","keyword":["Genetics (clinical)","Genetics","Molecular Biology"],"intvolume":"        13","citation":{"ama":"Puixeu Sala G, Macon A, Vicoso B. Sex-specific estimation of cis and trans regulation of gene expression in heads and gonads of Drosophila melanogaster. <i>G3: Genes, Genomes, Genetics</i>. 2023;13(8). doi:<a href=\"https://doi.org/10.1093/g3journal/jkad121\">10.1093/g3journal/jkad121</a>","short":"G. Puixeu Sala, A. Macon, B. Vicoso, G3: Genes, Genomes, Genetics 13 (2023).","mla":"Puixeu Sala, Gemma, et al. “Sex-Specific Estimation of Cis and Trans Regulation of Gene Expression in Heads and Gonads of Drosophila Melanogaster.” <i>G3: Genes, Genomes, Genetics</i>, vol. 13, no. 8, Oxford University Press, 2023, doi:<a href=\"https://doi.org/10.1093/g3journal/jkad121\">10.1093/g3journal/jkad121</a>.","ieee":"G. Puixeu Sala, A. Macon, and B. Vicoso, “Sex-specific estimation of cis and trans regulation of gene expression in heads and gonads of Drosophila melanogaster,” <i>G3: Genes, Genomes, Genetics</i>, vol. 13, no. 8. Oxford University Press, 2023.","chicago":"Puixeu Sala, Gemma, Ariana Macon, and Beatriz Vicoso. “Sex-Specific Estimation of Cis and Trans Regulation of Gene Expression in Heads and Gonads of Drosophila Melanogaster.” <i>G3: Genes, Genomes, Genetics</i>. Oxford University Press, 2023. <a href=\"https://doi.org/10.1093/g3journal/jkad121\">https://doi.org/10.1093/g3journal/jkad121</a>.","apa":"Puixeu Sala, G., Macon, A., &#38; Vicoso, B. (2023). Sex-specific estimation of cis and trans regulation of gene expression in heads and gonads of Drosophila melanogaster. <i>G3: Genes, Genomes, Genetics</i>. Oxford University Press. <a href=\"https://doi.org/10.1093/g3journal/jkad121\">https://doi.org/10.1093/g3journal/jkad121</a>","ista":"Puixeu Sala G, Macon A, Vicoso B. 2023. Sex-specific estimation of cis and trans regulation of gene expression in heads and gonads of Drosophila melanogaster. G3: Genes, Genomes, Genetics. 13(8)."},"doi":"10.1093/g3journal/jkad121","publisher":"Oxford University Press","language":[{"iso":"eng"}],"file_date_updated":"2023-11-07T09:00:19Z","type":"journal_article","oa_version":"Published Version","external_id":{"isi":["001002997200001"]},"date_published":"2023-08-01T00:00:00Z","issue":"8","publication":"G3: Genes, Genomes, Genetics","ddc":["570"],"author":[{"orcid":"0000-0001-8330-1754","id":"33AB266C-F248-11E8-B48F-1D18A9856A87","last_name":"Puixeu Sala","full_name":"Puixeu Sala, Gemma","first_name":"Gemma"},{"id":"2A0848E2-F248-11E8-B48F-1D18A9856A87","first_name":"Ariana","full_name":"Macon, Ariana","last_name":"Macon"},{"first_name":"Beatriz","full_name":"Vicoso, Beatriz","last_name":"Vicoso","orcid":"0000-0002-4579-8306","id":"49E1C5C6-F248-11E8-B48F-1D18A9856A87"}],"quality_controlled":"1","year":"2023","date_created":"2023-08-18T06:52:14Z","date_updated":"2023-12-13T12:15:37Z","acknowledged_ssus":[{"_id":"ScienComp"}],"project":[{"grant_number":"665385","name":"International IST Doctoral Program","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"_id":"9B9DFC9E-BA93-11EA-9121-9846C619BF3A","name":"Sexual conflict: resolution, constraints and biomedical implications","grant_number":"25817"}],"volume":13,"file":[{"file_size":845642,"creator":"dernst","relation":"main_file","checksum":"c62e29fc7c5efbf8356f4c60cab4a2d1","date_created":"2023-11-07T09:00:19Z","content_type":"application/pdf","file_id":"14498","access_level":"open_access","success":1,"date_updated":"2023-11-07T09:00:19Z","file_name":"2023_G3_Puixeu.pdf"}],"isi":1,"article_processing_charge":"Yes","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"publication_identifier":{"issn":["2160-1836"]},"scopus_import":"1"},{"article_type":"original","oa":1,"title":"Clinical, neuroradiological, and molecular characterization of mitochondrial threonyl-tRNA-synthetase (TARS2)-related disorder","publication_status":"published","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"14368","month":"11","abstract":[{"lang":"eng","text":"Purpose: \r\nBiallelic variants in TARS2, encoding the mitochondrial threonyl-tRNA-synthetase, have been reported in a small group of individuals displaying a neurodevelopmental phenotype but with limited neuroradiological data and insufficient evidence for causality of the variants.\r\nMethods:\r\nExome or genome sequencing was carried out in 15 families. Clinical and neuroradiological evaluation was performed for all affected individuals, including review of 10 previously reported individuals. The pathogenicity of TARS2 variants was evaluated using in vitro assays and a zebrafish model.\r\nResults:\r\nWe report 18 new individuals harboring biallelic TARS2 variants. Phenotypically, these individuals show developmental delay/intellectual disability, regression, cerebellar and cerebral atrophy, basal ganglia signal alterations, hypotonia, cerebellar signs, and increased blood lactate. In vitro studies showed that variants within the TARS2301-381 region had decreased binding to Rag GTPases, likely impairing mTORC1 activity. The zebrafish model recapitulated key features of the human phenotype and unraveled dysregulation of downstream targets of mTORC1 signaling. Functional testing of the variants confirmed the pathogenicity in a zebrafish model.\r\nConclusion:\r\nWe define the clinico-radiological spectrum of TARS2-related mitochondrial disease, unveil the likely involvement of the mTORC1 signaling pathway as a distinct molecular mechanism, and establish a TARS2 zebrafish model as an important tool to study variant pathogenicity."}],"extern":"1","article_number":"100938","status":"public","citation":{"ama":"Accogli A, Lin S-J, Severino M, et al. Clinical, neuroradiological, and molecular characterization of mitochondrial threonyl-tRNA-synthetase (TARS2)-related disorder. <i>Genetics in Medicine</i>. 2023;25(11). doi:<a href=\"https://doi.org/10.1016/j.gim.2023.100938\">10.1016/j.gim.2023.100938</a>","short":"A. Accogli, S.-J. Lin, M. Severino, S.-H. Kim, K. Huang, C. Rocca, M. Landsverk, M.S. Zaki, A. Al-Maawali, V.M. Srinivasan, K. Al-Thihli, G.B. Schaefer, M. Davis, D. Tonduti, C. Doneda, L.M. Marten, C. Mühlhausen, M. Gomez, E. Lamantea, R. Mena, M. Nizon, V. Procaccio, A. Begtrup, A. Telegrafi, H. Cui, H.L. Schulz, J. Mohr, S. Biskup, M.A. Loos, H.V. Aráoz, V. Salpietro, L.D. Keppen, M. Chitre, C. Petree, L. Raymond, J. Vogt, L.B. Sawyer, A.A. Basinger, S.V. Pedersen, T.S. Pearson, D.K. Grange, L. Lingappa, P. McDunnah, R. Horvath, B. Cognè, B. Isidor, A. Hahn, K.W. Gripp, S.M. Jafarnejad, E. Østergaard, C.E. Prada, D. Ghezzi, V.K. Gowda, R.W. Taylor, N. Sonenberg, H. Houlden, M. Sissler, G.K. Varshney, R. Maroofian, Genetics in Medicine 25 (2023).","ieee":"A. Accogli <i>et al.</i>, “Clinical, neuroradiological, and molecular characterization of mitochondrial threonyl-tRNA-synthetase (TARS2)-related disorder,” <i>Genetics in Medicine</i>, vol. 25, no. 11. Elsevier, 2023.","mla":"Accogli, Andrea, et al. “Clinical, Neuroradiological, and Molecular Characterization of Mitochondrial Threonyl-TRNA-Synthetase (TARS2)-Related Disorder.” <i>Genetics in Medicine</i>, vol. 25, no. 11, 100938, Elsevier, 2023, doi:<a href=\"https://doi.org/10.1016/j.gim.2023.100938\">10.1016/j.gim.2023.100938</a>.","chicago":"Accogli, Andrea, Sheng-Jia Lin, Mariasavina Severino, Sung-Hoon Kim, Kevin Huang, Clarissa Rocca, Megan Landsverk, et al. “Clinical, Neuroradiological, and Molecular Characterization of Mitochondrial Threonyl-TRNA-Synthetase (TARS2)-Related Disorder.” <i>Genetics in Medicine</i>. Elsevier, 2023. <a href=\"https://doi.org/10.1016/j.gim.2023.100938\">https://doi.org/10.1016/j.gim.2023.100938</a>.","apa":"Accogli, A., Lin, S.-J., Severino, M., Kim, S.-H., Huang, K., Rocca, C., … Maroofian, R. (2023). Clinical, neuroradiological, and molecular characterization of mitochondrial threonyl-tRNA-synthetase (TARS2)-related disorder. <i>Genetics in Medicine</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.gim.2023.100938\">https://doi.org/10.1016/j.gim.2023.100938</a>","ista":"Accogli A, Lin S-J, Severino M, Kim S-H, Huang K, Rocca C, Landsverk M, Zaki MS, Al-Maawali A, Srinivasan VM, Al-Thihli K, Schaefer GB, Davis M, Tonduti D, Doneda C, Marten LM, Mühlhausen C, Gomez M, Lamantea E, Mena R, Nizon M, Procaccio V, Begtrup A, Telegrafi A, Cui H, Schulz HL, Mohr J, Biskup S, Loos MA, Aráoz HV, Salpietro V, Keppen LD, Chitre M, Petree C, Raymond L, Vogt J, Sawyer LB, Basinger AA, Pedersen SV, Pearson TS, Grange DK, Lingappa L, McDunnah P, Horvath R, Cognè B, Isidor B, Hahn A, Gripp KW, Jafarnejad SM, Østergaard E, Prada CE, Ghezzi D, Gowda VK, Taylor RW, Sonenberg N, Houlden H, Sissler M, Varshney GK, Maroofian R. 2023. Clinical, neuroradiological, and molecular characterization of mitochondrial threonyl-tRNA-synthetase (TARS2)-related disorder. Genetics in Medicine. 25(11), 100938."},"intvolume":"        25","keyword":["Genetics (clinical)"],"has_accepted_license":"1","day":"01","file_date_updated":"2023-09-25T08:48:54Z","type":"journal_article","language":[{"iso":"eng"}],"publisher":"Elsevier","doi":"10.1016/j.gim.2023.100938","ddc":["570"],"author":[{"full_name":"Accogli, Andrea","first_name":"Andrea","last_name":"Accogli"},{"full_name":"Lin, Sheng-Jia","first_name":"Sheng-Jia","last_name":"Lin"},{"last_name":"Severino","first_name":"Mariasavina","full_name":"Severino, Mariasavina"},{"first_name":"Sung-Hoon","full_name":"Kim, Sung-Hoon","last_name":"Kim"},{"last_name":"Huang","first_name":"Kevin","full_name":"Huang, Kevin","orcid":"0000-0002-2512-7812","id":"3b3d2888-1ff6-11ee-9fa6-8f209ca91fe3"},{"first_name":"Clarissa","full_name":"Rocca, Clarissa","last_name":"Rocca"},{"full_name":"Landsverk, Megan","first_name":"Megan","last_name":"Landsverk"},{"last_name":"Zaki","full_name":"Zaki, Maha S.","first_name":"Maha S."},{"last_name":"Al-Maawali","first_name":"Almundher","full_name":"Al-Maawali, Almundher"},{"full_name":"Srinivasan, Varunvenkat M.","first_name":"Varunvenkat M.","last_name":"Srinivasan"},{"first_name":"Khalid","full_name":"Al-Thihli, Khalid","last_name":"Al-Thihli"},{"first_name":"G. Bradly","full_name":"Schaefer, G. Bradly","last_name":"Schaefer"},{"last_name":"Davis","full_name":"Davis, Monica","first_name":"Monica"},{"last_name":"Tonduti","full_name":"Tonduti, Davide","first_name":"Davide"},{"last_name":"Doneda","full_name":"Doneda, Chiara","first_name":"Chiara"},{"full_name":"Marten, Lara M.","first_name":"Lara M.","last_name":"Marten"},{"first_name":"Chris","full_name":"Mühlhausen, Chris","last_name":"Mühlhausen"},{"last_name":"Gomez","full_name":"Gomez, Maria","first_name":"Maria"},{"first_name":"Eleonora","full_name":"Lamantea, Eleonora","last_name":"Lamantea"},{"full_name":"Mena, Rafael","first_name":"Rafael","last_name":"Mena"},{"first_name":"Mathilde","full_name":"Nizon, Mathilde","last_name":"Nizon"},{"last_name":"Procaccio","first_name":"Vincent","full_name":"Procaccio, Vincent"},{"last_name":"Begtrup","full_name":"Begtrup, Amber","first_name":"Amber"},{"last_name":"Telegrafi","full_name":"Telegrafi, Aida","first_name":"Aida"},{"first_name":"Hong","full_name":"Cui, Hong","last_name":"Cui"},{"last_name":"Schulz","full_name":"Schulz, Heidi L.","first_name":"Heidi L."},{"full_name":"Mohr, Julia","first_name":"Julia","last_name":"Mohr"},{"last_name":"Biskup","full_name":"Biskup, Saskia","first_name":"Saskia"},{"last_name":"Loos","first_name":"Mariana Amina","full_name":"Loos, Mariana Amina"},{"full_name":"Aráoz, Hilda Verónica","first_name":"Hilda Verónica","last_name":"Aráoz"},{"first_name":"Vincenzo","full_name":"Salpietro, Vincenzo","last_name":"Salpietro"},{"full_name":"Keppen, Laura Davis","first_name":"Laura Davis","last_name":"Keppen"},{"last_name":"Chitre","full_name":"Chitre, Manali","first_name":"Manali"},{"first_name":"Cassidy","full_name":"Petree, Cassidy","last_name":"Petree"},{"first_name":"Lucy","full_name":"Raymond, Lucy","last_name":"Raymond"},{"last_name":"Vogt","first_name":"Julie","full_name":"Vogt, Julie"},{"first_name":"Lindsey B.","full_name":"Sawyer, Lindsey B.","last_name":"Sawyer"},{"full_name":"Basinger, Alice A.","first_name":"Alice A.","last_name":"Basinger"},{"first_name":"Signe Vandal","full_name":"Pedersen, Signe Vandal","last_name":"Pedersen"},{"last_name":"Pearson","full_name":"Pearson, Toni S.","first_name":"Toni S."},{"last_name":"Grange","full_name":"Grange, Dorothy K.","first_name":"Dorothy K."},{"full_name":"Lingappa, Lokesh","first_name":"Lokesh","last_name":"Lingappa"},{"first_name":"Paige","full_name":"McDunnah, Paige","last_name":"McDunnah"},{"full_name":"Horvath, Rita","first_name":"Rita","last_name":"Horvath"},{"first_name":"Benjamin","full_name":"Cognè, Benjamin","last_name":"Cognè"},{"last_name":"Isidor","full_name":"Isidor, Bertrand","first_name":"Bertrand"},{"last_name":"Hahn","full_name":"Hahn, Andreas","first_name":"Andreas"},{"last_name":"Gripp","full_name":"Gripp, Karen W.","first_name":"Karen W."},{"last_name":"Jafarnejad","first_name":"Seyed Mehdi","full_name":"Jafarnejad, Seyed Mehdi"},{"first_name":"Elsebet","full_name":"Østergaard, Elsebet","last_name":"Østergaard"},{"full_name":"Prada, Carlos E.","first_name":"Carlos E.","last_name":"Prada"},{"last_name":"Ghezzi","first_name":"Daniele","full_name":"Ghezzi, Daniele"},{"first_name":"Vykuntaraju K.","full_name":"Gowda, Vykuntaraju K.","last_name":"Gowda"},{"last_name":"Taylor","first_name":"Robert W.","full_name":"Taylor, Robert W."},{"first_name":"Nahum","full_name":"Sonenberg, Nahum","last_name":"Sonenberg"},{"full_name":"Houlden, Henry","first_name":"Henry","last_name":"Houlden"},{"last_name":"Sissler","full_name":"Sissler, Marie","first_name":"Marie"},{"first_name":"Gaurav K.","full_name":"Varshney, Gaurav K.","last_name":"Varshney"},{"last_name":"Maroofian","full_name":"Maroofian, Reza","first_name":"Reza"}],"issue":"11","publication":"Genetics in Medicine","date_published":"2023-11-01T00:00:00Z","oa_version":"Published Version","volume":25,"file":[{"content_type":"application/pdf","date_created":"2023-09-25T08:48:54Z","file_id":"14369","date_updated":"2023-09-25T08:48:54Z","access_level":"open_access","success":1,"file_name":"2023_GeneticsMedicine_Accogli.pdf","file_size":4105513,"creator":"dernst","relation":"main_file","checksum":"440f0cd8a2ffcbe03c015c1746728387"}],"date_updated":"2023-09-25T08:50:10Z","quality_controlled":"1","year":"2023","date_created":"2023-09-25T08:44:29Z","scopus_import":"1","publication_identifier":{"issn":["1098-3600"]},"article_processing_charge":"No","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"}},{"volume":40,"file":[{"file_size":8623505,"creator":"dernst","relation":"main_file","checksum":"47c1c72fb499f26ea52d216b242208c8","date_created":"2024-01-02T11:39:38Z","file_id":"14727","content_type":"application/pdf","date_updated":"2024-01-02T11:39:38Z","success":1,"access_level":"open_access","file_name":"2023_MolecularBioEvo_Lasne.pdf"}],"date_updated":"2024-02-21T12:18:35Z","acknowledged_ssus":[{"_id":"ScienComp"}],"project":[{"_id":"34ae1506-11ca-11ed-8bc3-c14f4c474396","grant_number":"F8810","name":"The highjacking of meiosis for asexual reproduction"},{"_id":"ebb230e0-77a9-11ec-83b8-87a37e0241d3","name":"Mechanisms and Evolution of Reproductive Plasticity","grant_number":"ESP39 49461"}],"quality_controlled":"1","year":"2023","date_created":"2023-11-27T16:14:37Z","scopus_import":"1","pmid":1,"publication_identifier":{"issn":["0737-4038"],"eissn":["1537-1719"]},"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"article_processing_charge":"Yes (via OA deal)","file_date_updated":"2024-01-02T11:39:38Z","type":"journal_article","language":[{"iso":"eng"}],"publisher":"Oxford University Press","doi":"10.1093/molbev/msad245","ddc":["570"],"author":[{"orcid":"0000-0002-1197-8616","id":"02225f57-50d2-11eb-9ed8-8c92b9a34237","full_name":"Lasne, Clementine","first_name":"Clementine","last_name":"Lasne"},{"orcid":"0000-0002-5328-7231","id":"0B46FACA-A8E1-11E9-9BD3-79D1E5697425","last_name":"Elkrewi","first_name":"Marwan N","full_name":"Elkrewi, Marwan N"},{"orcid":"0000-0002-9752-7380","id":"4E099E4E-F248-11E8-B48F-1D18A9856A87","last_name":"Toups","first_name":"Melissa A","full_name":"Toups, Melissa A"},{"id":"02814589-eb8f-11eb-b029-a70074f3f18f","orcid":"0000-0002-1253-6297","full_name":"Layana Franco, Lorena Alexandra","first_name":"Lorena Alexandra","last_name":"Layana Franco"},{"id":"2A0848E2-F248-11E8-B48F-1D18A9856A87","first_name":"Ariana","full_name":"Macon, Ariana","last_name":"Macon"},{"last_name":"Vicoso","first_name":"Beatriz","full_name":"Vicoso, Beatriz","id":"49E1C5C6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4579-8306"}],"publication":"Molecular Biology and Evolution","issue":"12","date_published":"2023-12-01T00:00:00Z","oa_version":"Published Version","external_id":{"pmid":["37988296"]},"abstract":[{"lang":"eng","text":"Many insects carry an ancient X chromosome - the Drosophila Muller element F - that likely predates their origin. Interestingly, the X has undergone turnover in multiple fly species (Diptera) after being conserved for more than 450 MY. The long evolutionary distance between Diptera and other sequenced insect clades makes it difficult to infer what could have contributed to this sudden increase in rate of turnover. Here, we produce the first genome and transcriptome of a long overlooked sister-order to Diptera: Mecoptera. We compare the scorpionfly Panorpa cognata X-chromosome gene content, expression, and structure, to that of several dipteran species as well as more distantly-related insect orders (Orthoptera and Blattodea). We find high conservation of gene content between the mecopteran X and the dipteran Muller F element, as well as several shared biological features, such as the presence of dosage compensation and a low amount of genetic diversity, consistent with a low recombination rate. However, the two homologous X chromosomes differ strikingly in their size and number of genes they carry. Our results therefore support a common ancestry of the mecopteran and ancestral dipteran X chromosomes, and suggest that Muller element F shrank in size and gene content after the split of Diptera and Mecoptera, which may have contributed to its turnover in dipteran insects."}],"article_number":"msad245","status":"public","citation":{"short":"C. Lasne, M.N. Elkrewi, M.A. Toups, L.A. Layana Franco, A. Macon, B. Vicoso, Molecular Biology and Evolution 40 (2023).","ama":"Lasne C, Elkrewi MN, Toups MA, Layana Franco LA, Macon A, Vicoso B. The scorpionfly (Panorpa cognata) genome highlights conserved and derived features of the peculiar dipteran X chromosome. <i>Molecular Biology and Evolution</i>. 2023;40(12). doi:<a href=\"https://doi.org/10.1093/molbev/msad245\">10.1093/molbev/msad245</a>","apa":"Lasne, C., Elkrewi, M. N., Toups, M. A., Layana Franco, L. A., Macon, A., &#38; Vicoso, B. (2023). The scorpionfly (Panorpa cognata) genome highlights conserved and derived features of the peculiar dipteran X chromosome. <i>Molecular Biology and Evolution</i>. Oxford University Press. <a href=\"https://doi.org/10.1093/molbev/msad245\">https://doi.org/10.1093/molbev/msad245</a>","chicago":"Lasne, Clementine, Marwan N Elkrewi, Melissa A Toups, Lorena Alexandra Layana Franco, Ariana Macon, and Beatriz Vicoso. “The Scorpionfly (Panorpa Cognata) Genome Highlights Conserved and Derived Features of the Peculiar Dipteran X Chromosome.” <i>Molecular Biology and Evolution</i>. Oxford University Press, 2023. <a href=\"https://doi.org/10.1093/molbev/msad245\">https://doi.org/10.1093/molbev/msad245</a>.","ista":"Lasne C, Elkrewi MN, Toups MA, Layana Franco LA, Macon A, Vicoso B. 2023. The scorpionfly (Panorpa cognata) genome highlights conserved and derived features of the peculiar dipteran X chromosome. Molecular Biology and Evolution. 40(12), msad245.","mla":"Lasne, Clementine, et al. “The Scorpionfly (Panorpa Cognata) Genome Highlights Conserved and Derived Features of the Peculiar Dipteran X Chromosome.” <i>Molecular Biology and Evolution</i>, vol. 40, no. 12, msad245, Oxford University Press, 2023, doi:<a href=\"https://doi.org/10.1093/molbev/msad245\">10.1093/molbev/msad245</a>.","ieee":"C. Lasne, M. N. Elkrewi, M. A. Toups, L. A. Layana Franco, A. Macon, and B. Vicoso, “The scorpionfly (Panorpa cognata) genome highlights conserved and derived features of the peculiar dipteran X chromosome,” <i>Molecular Biology and Evolution</i>, vol. 40, no. 12. Oxford University Press, 2023."},"intvolume":"        40","keyword":["Genetics","Molecular Biology","Ecology","Evolution","Behavior and Systematics"],"has_accepted_license":"1","day":"01","article_type":"original","related_material":{"record":[{"status":"public","relation":"research_data","id":"14614"}],"link":[{"url":"https://ista.ac.at/en/news/on-the-hunt/","description":"News on ISTA webpage","relation":"press_release"}]},"title":"The scorpionfly (Panorpa cognata) genome highlights conserved and derived features of the peculiar dipteran X chromosome","oa":1,"publication_status":"published","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"12","_id":"14613","department":[{"_id":"BeVi"}],"acknowledgement":"We thank the Vicoso lab for their assistance with specimen collection, and Tim Connallon for valuable comments and suggestions on earlier versions of the manuscript. Computational resources and support were provided by the Scientific Computing unit at the ISTA. This research was supported by grants from the Austrian Science Foundation to C.L.\r\n(FWF ESP 39), and to B.V. (FWF SFB F88-10)."},{"keyword":["Genetics (clinical)","Genetics","Molecular Biology","Molecular Medicine"],"citation":{"ama":"Lin S-J, Vona B, Lau T, et al. Evaluating the association of biallelic OGDHL variants with significant phenotypic heterogeneity. <i>Genome Medicine</i>. 2023;15. doi:<a href=\"https://doi.org/10.1186/s13073-023-01258-4\">10.1186/s13073-023-01258-4</a>","short":"S.-J. Lin, B. Vona, T. Lau, K. Huang, M.S. Zaki, H.S. Aldeen, E.G. Karimiani, C. Rocca, M.M. Noureldeen, A.K. Saad, C. Petree, T. Bartolomaeus, R. Abou Jamra, G. Zifarelli, A. Gotkhindikar, I.M. Wentzensen, M. Liao, E.E. Cork, P. Varshney, N. Hashemi, M.H. Mohammadi, A. Rad, J. Neira, M.B. Toosi, C. Knopp, I. Kurth, T.D. Challman, R. Smith, A. Abdalla, T. Haaf, M. Suri, M. Joshi, W.K. Chung, A. Moreno-De-Luca, H. Houlden, R. Maroofian, G.K. Varshney, Genome Medicine 15 (2023).","ieee":"S.-J. Lin <i>et al.</i>, “Evaluating the association of biallelic OGDHL variants with significant phenotypic heterogeneity,” <i>Genome Medicine</i>, vol. 15. Springer Nature, 2023.","mla":"Lin, Sheng-Jia, et al. “Evaluating the Association of Biallelic OGDHL Variants with Significant Phenotypic Heterogeneity.” <i>Genome Medicine</i>, vol. 15, 102, Springer Nature, 2023, doi:<a href=\"https://doi.org/10.1186/s13073-023-01258-4\">10.1186/s13073-023-01258-4</a>.","ista":"Lin S-J, Vona B, Lau T, Huang K, Zaki MS, Aldeen HS, Karimiani EG, Rocca C, Noureldeen MM, Saad AK, Petree C, Bartolomaeus T, Abou Jamra R, Zifarelli G, Gotkhindikar A, Wentzensen IM, Liao M, Cork EE, Varshney P, Hashemi N, Mohammadi MH, Rad A, Neira J, Toosi MB, Knopp C, Kurth I, Challman TD, Smith R, Abdalla A, Haaf T, Suri M, Joshi M, Chung WK, Moreno-De-Luca A, Houlden H, Maroofian R, Varshney GK. 2023. Evaluating the association of biallelic OGDHL variants with significant phenotypic heterogeneity. Genome Medicine. 15, 102.","chicago":"Lin, Sheng-Jia, Barbara Vona, Tracy Lau, Kevin Huang, Maha S. Zaki, Huda Shujaa Aldeen, Ehsan Ghayoor Karimiani, et al. “Evaluating the Association of Biallelic OGDHL Variants with Significant Phenotypic Heterogeneity.” <i>Genome Medicine</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1186/s13073-023-01258-4\">https://doi.org/10.1186/s13073-023-01258-4</a>.","apa":"Lin, S.-J., Vona, B., Lau, T., Huang, K., Zaki, M. S., Aldeen, H. S., … Varshney, G. K. (2023). Evaluating the association of biallelic OGDHL variants with significant phenotypic heterogeneity. <i>Genome Medicine</i>. Springer Nature. <a href=\"https://doi.org/10.1186/s13073-023-01258-4\">https://doi.org/10.1186/s13073-023-01258-4</a>"},"intvolume":"        15","day":"23","has_accepted_license":"1","status":"public","article_number":"102","extern":"1","abstract":[{"lang":"eng","text":"Background: Biallelic variants in OGDHL, encoding part of the α-ketoglutarate dehydrogenase complex, have been associated with highly heterogeneous neurological and neurodevelopmental disorders. However, the validity of this association remains to be confirmed. A second OGDHL patient cohort was recruited to carefully assess the gene-disease relationship.\r\nMethods: Using an unbiased genotype-first approach, we screened large, multiethnic aggregated sequencing datasets worldwide for biallelic OGDHL variants. We used CRISPR/Cas9 to generate zebrafish knockouts of ogdhl, ogdh paralogs, and dhtkd1 to investigate functional relationships and impact during development. Functional complementation with patient variant transcripts was conducted to systematically assess protein functionality as a readout for pathogenicity.\r\nResults: A cohort of 14 individuals from 12 unrelated families exhibited highly variable clinical phenotypes, with the majority of them presenting at least one additional variant, potentially accounting for a blended phenotype and complicating phenotypic understanding. We also uncovered extreme clinical heterogeneity and high allele frequencies, occasionally incompatible with a fully penetrant recessive disorder. Human cDNA of previously described and new variants were tested in an ogdhl zebrafish knockout model, adding functional evidence for variant reclassification. We disclosed evidence of hypomorphic alleles as well as a loss-of-function variant without deleterious effects in zebrafish variant testing also showing discordant familial segregation, challenging the relationship of OGDHL as a conventional Mendelian gene. Going further, we uncovered evidence for a complex compensatory relationship among OGDH, OGDHL, and DHTKD1 isoenzymes that are associated with neurodevelopmental disorders and exhibit complex transcriptional compensation patterns with partial functional redundancy.\r\nConclusions: Based on the results of genetic, clinical, and functional studies, we formed three hypotheses in which to frame observations: biallelic OGDHL variants lead to a highly variable monogenic disorder, variants in OGDHL are following a complex pattern of inheritance, or they may not be causative at all. Our study further highlights the continuing challenges of assessing the validity of reported disease-gene associations and effects of variants identified in these genes. This is particularly more complicated in making genetic diagnoses based on identification of variants in genes presenting a highly heterogenous phenotype such as “OGDHL-related disorders”."}],"publication_status":"published","oa":1,"title":"Evaluating the association of biallelic OGDHL variants with significant phenotypic heterogeneity","article_type":"original","month":"11","_id":"14639","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication_identifier":{"issn":["1756-994X"]},"article_processing_charge":"Yes","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"file":[{"file_size":14791081,"creator":"dernst","relation":"main_file","checksum":"279efd212005549aba817a487d56d363","content_type":"application/pdf","date_created":"2023-12-04T08:15:43Z","file_id":"14640","access_level":"open_access","date_updated":"2023-12-04T08:15:43Z","success":1,"file_name":"2023_GenomeMed_Lin.pdf"}],"volume":15,"year":"2023","date_created":"2023-12-04T08:10:55Z","quality_controlled":"1","date_updated":"2023-12-04T08:17:22Z","publication":"Genome Medicine","author":[{"full_name":"Lin, Sheng-Jia","first_name":"Sheng-Jia","last_name":"Lin"},{"first_name":"Barbara","full_name":"Vona, Barbara","last_name":"Vona"},{"first_name":"Tracy","full_name":"Lau, Tracy","last_name":"Lau"},{"orcid":"0000-0002-2512-7812","id":"3b3d2888-1ff6-11ee-9fa6-8f209ca91fe3","first_name":"Kevin","full_name":"Huang, Kevin","last_name":"Huang"},{"last_name":"Zaki","first_name":"Maha S.","full_name":"Zaki, Maha S."},{"full_name":"Aldeen, Huda Shujaa","first_name":"Huda Shujaa","last_name":"Aldeen"},{"full_name":"Karimiani, Ehsan Ghayoor","first_name":"Ehsan Ghayoor","last_name":"Karimiani"},{"last_name":"Rocca","first_name":"Clarissa","full_name":"Rocca, Clarissa"},{"full_name":"Noureldeen, Mahmoud M.","first_name":"Mahmoud M.","last_name":"Noureldeen"},{"last_name":"Saad","full_name":"Saad, Ahmed K.","first_name":"Ahmed K."},{"last_name":"Petree","first_name":"Cassidy","full_name":"Petree, Cassidy"},{"full_name":"Bartolomaeus, Tobias","first_name":"Tobias","last_name":"Bartolomaeus"},{"full_name":"Abou Jamra, Rami","first_name":"Rami","last_name":"Abou Jamra"},{"first_name":"Giovanni","full_name":"Zifarelli, Giovanni","last_name":"Zifarelli"},{"first_name":"Aditi","full_name":"Gotkhindikar, Aditi","last_name":"Gotkhindikar"},{"first_name":"Ingrid M.","full_name":"Wentzensen, Ingrid M.","last_name":"Wentzensen"},{"last_name":"Liao","first_name":"Mingjuan","full_name":"Liao, Mingjuan"},{"last_name":"Cork","full_name":"Cork, Emalyn Elise","first_name":"Emalyn Elise"},{"first_name":"Pratishtha","full_name":"Varshney, Pratishtha","last_name":"Varshney"},{"last_name":"Hashemi","full_name":"Hashemi, Narges","first_name":"Narges"},{"last_name":"Mohammadi","full_name":"Mohammadi, Mohammad Hasan","first_name":"Mohammad Hasan"},{"last_name":"Rad","full_name":"Rad, Aboulfazl","first_name":"Aboulfazl"},{"last_name":"Neira","first_name":"Juanita","full_name":"Neira, Juanita"},{"first_name":"Mehran Beiraghi","full_name":"Toosi, Mehran Beiraghi","last_name":"Toosi"},{"last_name":"Knopp","first_name":"Cordula","full_name":"Knopp, Cordula"},{"last_name":"Kurth","full_name":"Kurth, Ingo","first_name":"Ingo"},{"last_name":"Challman","full_name":"Challman, Thomas D.","first_name":"Thomas D."},{"last_name":"Smith","first_name":"Rebecca","full_name":"Smith, Rebecca"},{"full_name":"Abdalla, Asmahan","first_name":"Asmahan","last_name":"Abdalla"},{"full_name":"Haaf, Thomas","first_name":"Thomas","last_name":"Haaf"},{"last_name":"Suri","first_name":"Mohnish","full_name":"Suri, Mohnish"},{"first_name":"Manali","full_name":"Joshi, Manali","last_name":"Joshi"},{"last_name":"Chung","full_name":"Chung, Wendy K.","first_name":"Wendy K."},{"last_name":"Moreno-De-Luca","first_name":"Andres","full_name":"Moreno-De-Luca, Andres"},{"first_name":"Henry","full_name":"Houlden, Henry","last_name":"Houlden"},{"last_name":"Maroofian","full_name":"Maroofian, Reza","first_name":"Reza"},{"first_name":"Gaurav K.","full_name":"Varshney, Gaurav K.","last_name":"Varshney"}],"ddc":["570"],"oa_version":"Published Version","date_published":"2023-11-23T00:00:00Z","language":[{"iso":"eng"}],"type":"journal_article","file_date_updated":"2023-12-04T08:15:43Z","doi":"10.1186/s13073-023-01258-4","publisher":"Springer Nature"},{"quality_controlled":"1","date_created":"2023-12-13T11:48:05Z","year":"2023","date_updated":"2023-12-18T08:06:14Z","project":[{"_id":"268F8446-B435-11E9-9278-68D0E5697425","grant_number":"T0101031","name":"Role of Eed in neural stem cell lineage progression","call_identifier":"FWF"},{"name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411","_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"name":"Molecular Mechanisms of Neural Stem Cell Lineage Progression","grant_number":"F07805","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E"},{"call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425","grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"volume":5,"article_processing_charge":"No","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"publication_identifier":{"issn":["2666-1667"]},"scopus_import":"1","pmid":1,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1016/j.xpro.2023.102771"}],"doi":"10.1016/j.xpro.2023.102771","publisher":"Elsevier","language":[{"iso":"eng"}],"type":"journal_article","oa_version":"Submitted Version","external_id":{"pmid":["38070137"]},"date_published":"2023-12-08T00:00:00Z","publication":"STAR Protocols","issue":"1","ddc":["570"],"author":[{"full_name":"Amberg, Nicole","first_name":"Nicole","last_name":"Amberg","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3183-8207"},{"first_name":"Giselle T","full_name":"Cheung, Giselle T","last_name":"Cheung","id":"471195F6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8457-2572"},{"last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061"}],"ec_funded":1,"article_number":"102771","status":"public","abstract":[{"lang":"eng","text":"Mosaic analysis with double markers (MADM) technology enables the generation of genetic mosaic tissue in mice and high-resolution phenotyping at the individual cell level. Here, we present a protocol for isolating MADM-labeled cells with high yield for downstream molecular analyses using fluorescence-activated cell sorting (FACS). We describe steps for generating MADM-labeled mice, perfusion, single-cell suspension, and debris removal. We then detail procedures for cell sorting by FACS and downstream analysis. This protocol is suitable for embryonic to adult mice.\r\nFor complete details on the use and execution of this protocol, please refer to Contreras et al. (2021).1"}],"day":"08","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Neuroscience"],"intvolume":"         5","citation":{"short":"N. Amberg, G.T. Cheung, S. Hippenmeyer, STAR Protocols 5 (2023).","ama":"Amberg N, Cheung GT, Hippenmeyer S. Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry. <i>STAR Protocols</i>. 2023;5(1). doi:<a href=\"https://doi.org/10.1016/j.xpro.2023.102771\">10.1016/j.xpro.2023.102771</a>","chicago":"Amberg, Nicole, Giselle T Cheung, and Simon Hippenmeyer. “Protocol for Sorting Cells from Mouse Brains Labeled with Mosaic Analysis with Double Markers by Flow Cytometry.” <i>STAR Protocols</i>. Elsevier, 2023. <a href=\"https://doi.org/10.1016/j.xpro.2023.102771\">https://doi.org/10.1016/j.xpro.2023.102771</a>.","ista":"Amberg N, Cheung GT, Hippenmeyer S. 2023. Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry. STAR Protocols. 5(1), 102771.","apa":"Amberg, N., Cheung, G. T., &#38; Hippenmeyer, S. (2023). Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry. <i>STAR Protocols</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.xpro.2023.102771\">https://doi.org/10.1016/j.xpro.2023.102771</a>","ieee":"N. Amberg, G. T. Cheung, and S. Hippenmeyer, “Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry,” <i>STAR Protocols</i>, vol. 5, no. 1. Elsevier, 2023.","mla":"Amberg, Nicole, et al. “Protocol for Sorting Cells from Mouse Brains Labeled with Mosaic Analysis with Double Markers by Flow Cytometry.” <i>STAR Protocols</i>, vol. 5, no. 1, 102771, Elsevier, 2023, doi:<a href=\"https://doi.org/10.1016/j.xpro.2023.102771\">10.1016/j.xpro.2023.102771</a>."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"12","_id":"14683","oa":1,"title":"Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry","publication_status":"epub_ahead","article_type":"review","department":[{"_id":"SiHi"}],"acknowledgement":"This research was supported by the Scientific Service Units (SSU) at IST Austria through resources provided by the Imaging & Optics Facility (IOF) and Preclinical Facilities (PCF). N.A. received support from FWF Firnberg-Programme (T 1031). G.C. received support from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 754411 as an ISTplus postdoctoral fellow. This work was also supported by IST Austria institutional funds, FWF SFB F78 to S.H., and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement no. 725780 LinPro) to S.H."},{"author":[{"full_name":"Lucek, Kay","first_name":"Kay","last_name":"Lucek"},{"last_name":"Giménez","first_name":"Mabel D.","full_name":"Giménez, Mabel D."},{"last_name":"Joron","first_name":"Mathieu","full_name":"Joron, Mathieu"},{"last_name":"Rafajlović","full_name":"Rafajlović, Marina","first_name":"Marina"},{"last_name":"Searle","first_name":"Jeremy B.","full_name":"Searle, Jeremy B."},{"last_name":"Walden","first_name":"Nora","full_name":"Walden, Nora"},{"first_name":"Anja M","full_name":"Westram, Anja M","last_name":"Westram","id":"3C147470-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1050-4969"},{"last_name":"Faria","first_name":"Rui","full_name":"Faria, Rui"}],"issue":"11","publication":"Cold Spring Harbor Perspectives in Biology","date_published":"2023-11-01T00:00:00Z","external_id":{"pmid":["37604585"]},"oa_version":"Published Version","type":"journal_article","language":[{"iso":"eng"}],"publisher":"Cold Spring Harbor Laboratory","doi":"10.1101/cshperspect.a041447","scopus_import":"1","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/cshperspect.a041447"}],"pmid":1,"publication_identifier":{"issn":["1943-0264"]},"article_processing_charge":"No","volume":15,"date_updated":"2024-01-08T12:52:29Z","quality_controlled":"1","date_created":"2024-01-08T12:43:48Z","year":"2023","department":[{"_id":"NiBa"},{"_id":"BeVi"}],"acknowledgement":"K.L. was funded by a Swiss National Science Foundation Eccellenza project: The evolution of strong reproductive barriers towards the completion of speciation (PCEFP3_202869). R.F.\r\nwas funded by an FCT CEEC (Fundação para a Ciênca e a Tecnologia, Concurso Estímulo ao\r\nEmprego Científico) contract (2020.00275. CEECIND) and by an FCT research project\r\n(PTDC/BIA-EVL/1614/2021). M.R. was funded by the Swedish Research Council Vetenskapsrådet (grant number 2021-05243). A.M.W. was partly funded by the Norwegian Research Council RCN. We thank Luis Silva for his help preparing Figure 1. We are grateful to Maren Wellenreuther, Daniel Bolnick, and two anonymous reviewers for their constructive feedback on an earlier version of this paper.","article_type":"original","title":"The impact of chromosomal rearrangements in speciation: From micro- to macroevolution","oa":1,"publication_status":"published","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"11","_id":"14742","citation":{"ama":"Lucek K, Giménez MD, Joron M, et al. The impact of chromosomal rearrangements in speciation: From micro- to macroevolution. <i>Cold Spring Harbor Perspectives in Biology</i>. 2023;15(11). doi:<a href=\"https://doi.org/10.1101/cshperspect.a041447\">10.1101/cshperspect.a041447</a>","short":"K. Lucek, M.D. Giménez, M. Joron, M. Rafajlović, J.B. Searle, N. Walden, A.M. Westram, R. Faria, Cold Spring Harbor Perspectives in Biology 15 (2023).","mla":"Lucek, Kay, et al. “The Impact of Chromosomal Rearrangements in Speciation: From Micro- to Macroevolution.” <i>Cold Spring Harbor Perspectives in Biology</i>, vol. 15, no. 11, a041447, Cold Spring Harbor Laboratory, 2023, doi:<a href=\"https://doi.org/10.1101/cshperspect.a041447\">10.1101/cshperspect.a041447</a>.","ieee":"K. Lucek <i>et al.</i>, “The impact of chromosomal rearrangements in speciation: From micro- to macroevolution,” <i>Cold Spring Harbor Perspectives in Biology</i>, vol. 15, no. 11. Cold Spring Harbor Laboratory, 2023.","chicago":"Lucek, Kay, Mabel D. Giménez, Mathieu Joron, Marina Rafajlović, Jeremy B. Searle, Nora Walden, Anja M Westram, and Rui Faria. “The Impact of Chromosomal Rearrangements in Speciation: From Micro- to Macroevolution.” <i>Cold Spring Harbor Perspectives in Biology</i>. Cold Spring Harbor Laboratory, 2023. <a href=\"https://doi.org/10.1101/cshperspect.a041447\">https://doi.org/10.1101/cshperspect.a041447</a>.","apa":"Lucek, K., Giménez, M. D., Joron, M., Rafajlović, M., Searle, J. B., Walden, N., … Faria, R. (2023). The impact of chromosomal rearrangements in speciation: From micro- to macroevolution. <i>Cold Spring Harbor Perspectives in Biology</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/cshperspect.a041447\">https://doi.org/10.1101/cshperspect.a041447</a>","ista":"Lucek K, Giménez MD, Joron M, Rafajlović M, Searle JB, Walden N, Westram AM, Faria R. 2023. The impact of chromosomal rearrangements in speciation: From micro- to macroevolution. Cold Spring Harbor Perspectives in Biology. 15(11), a041447."},"intvolume":"        15","keyword":["General Biochemistry","Genetics and Molecular Biology"],"day":"01","abstract":[{"lang":"eng","text":"Chromosomal rearrangements (CRs) have been known since almost the beginning of genetics.\r\nWhile an important role for CRs in speciation has been suggested, evidence primarily stems\r\nfrom theoretical and empirical studies focusing on the microevolutionary level (i.e., on taxon\r\npairs where speciation is often incomplete). Although the role of CRs in eukaryotic speciation at\r\na macroevolutionary level has been supported by associations between species diversity and\r\nrates of evolution of CRs across phylogenies, these findings are limited to a restricted range of\r\nCRs and taxa. Now that more broadly applicable and precise CR detection approaches have\r\nbecome available, we address the challenges in filling some of the conceptual and empirical\r\ngaps between micro- and macroevolutionary studies on the role of CRs in speciation. We\r\nsynthesize what is known about the macroevolutionary impact of CRs and suggest new research avenues to overcome the pitfalls of previous studies to gain a more comprehensive understanding of the evolutionary significance of CRs in speciation across the tree of life."}],"article_number":"a041447","status":"public"},{"pmid":1,"main_file_link":[{"url":"https://www.biorxiv.org/content/10.1101/2023.07.09.548244","open_access":"1"}],"publication_identifier":{"issn":["1534-5807"]},"article_processing_charge":"No","volume":58,"date_updated":"2024-01-16T08:56:36Z","quality_controlled":"1","page":"1578-1592.e5","year":"2023","date_created":"2024-01-10T09:41:21Z","author":[{"first_name":"Kim Joana","full_name":"Westerich, Kim Joana","last_name":"Westerich"},{"first_name":"Katsiaryna","full_name":"Tarbashevich, Katsiaryna","last_name":"Tarbashevich"},{"last_name":"Schick","first_name":"Jan","full_name":"Schick, Jan"},{"full_name":"Gupta, Antra","first_name":"Antra","last_name":"Gupta"},{"first_name":"Mingzhao","full_name":"Zhu, Mingzhao","last_name":"Zhu"},{"last_name":"Hull","full_name":"Hull, Kenneth","first_name":"Kenneth"},{"last_name":"Romo","first_name":"Daniel","full_name":"Romo, Daniel"},{"first_name":"Dagmar","full_name":"Zeuschner, Dagmar","last_name":"Zeuschner"},{"id":"3384113A-F248-11E8-B48F-1D18A9856A87","full_name":"Goudarzi, Mohammad","first_name":"Mohammad","last_name":"Goudarzi"},{"first_name":"Theresa","full_name":"Gross-Thebing, Theresa","last_name":"Gross-Thebing"},{"last_name":"Raz","first_name":"Erez","full_name":"Raz, Erez"}],"publication":"Developmental Cell","issue":"17","date_published":"2023-09-11T00:00:00Z","external_id":{"pmid":["37463577"]},"oa_version":"Preprint","type":"journal_article","language":[{"iso":"eng"}],"publisher":"Elsevier","doi":"10.1016/j.devcel.2023.06.009","citation":{"chicago":"Westerich, Kim Joana, Katsiaryna Tarbashevich, Jan Schick, Antra Gupta, Mingzhao Zhu, Kenneth Hull, Daniel Romo, et al. “Spatial Organization and Function of RNA Molecules within Phase-Separated Condensates in Zebrafish Are Controlled by Dnd1.” <i>Developmental Cell</i>. Elsevier, 2023. <a href=\"https://doi.org/10.1016/j.devcel.2023.06.009\">https://doi.org/10.1016/j.devcel.2023.06.009</a>.","ista":"Westerich KJ, Tarbashevich K, Schick J, Gupta A, Zhu M, Hull K, Romo D, Zeuschner D, Goudarzi M, Gross-Thebing T, Raz E. 2023. Spatial organization and function of RNA molecules within phase-separated condensates in zebrafish are controlled by Dnd1. Developmental Cell. 58(17), 1578–1592.e5.","apa":"Westerich, K. J., Tarbashevich, K., Schick, J., Gupta, A., Zhu, M., Hull, K., … Raz, E. (2023). Spatial organization and function of RNA molecules within phase-separated condensates in zebrafish are controlled by Dnd1. <i>Developmental Cell</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.devcel.2023.06.009\">https://doi.org/10.1016/j.devcel.2023.06.009</a>","mla":"Westerich, Kim Joana, et al. “Spatial Organization and Function of RNA Molecules within Phase-Separated Condensates in Zebrafish Are Controlled by Dnd1.” <i>Developmental Cell</i>, vol. 58, no. 17, Elsevier, 2023, p. 1578–1592.e5, doi:<a href=\"https://doi.org/10.1016/j.devcel.2023.06.009\">10.1016/j.devcel.2023.06.009</a>.","ieee":"K. J. Westerich <i>et al.</i>, “Spatial organization and function of RNA molecules within phase-separated condensates in zebrafish are controlled by Dnd1,” <i>Developmental Cell</i>, vol. 58, no. 17. Elsevier, p. 1578–1592.e5, 2023.","short":"K.J. Westerich, K. Tarbashevich, J. Schick, A. Gupta, M. Zhu, K. Hull, D. Romo, D. Zeuschner, M. Goudarzi, T. Gross-Thebing, E. Raz, Developmental Cell 58 (2023) 1578–1592.e5.","ama":"Westerich KJ, Tarbashevich K, Schick J, et al. Spatial organization and function of RNA molecules within phase-separated condensates in zebrafish are controlled by Dnd1. <i>Developmental Cell</i>. 2023;58(17):1578-1592.e5. doi:<a href=\"https://doi.org/10.1016/j.devcel.2023.06.009\">10.1016/j.devcel.2023.06.009</a>"},"intvolume":"        58","keyword":["Developmental Biology","Cell Biology","General Biochemistry","Genetics and Molecular Biology","Molecular Biology"],"day":"11","abstract":[{"text":"Germ granules, condensates of phase-separated RNA and protein, are organelles that are essential for germline development in different organisms. The patterning of the granules and their relevance for germ cell fate are not fully understood. Combining three-dimensional in vivo structural and functional analyses, we study the dynamic spatial organization of molecules within zebrafish germ granules. We find that the localization of RNA molecules to the periphery of the granules, where ribosomes are localized, depends on translational activity at this location. In addition, we find that the vertebrate-specific Dead end (Dnd1) protein is essential for nanos3 RNA localization at the condensates’ periphery. Accordingly, in the absence of Dnd1, or when translation is inhibited, nanos3 RNA translocates into the granule interior, away from the ribosomes, a process that is correlated with the loss of germ cell fate. These findings highlight the relevance of sub-granule compartmentalization for post-transcriptional control and its importance for preserving germ cell totipotency.","lang":"eng"}],"status":"public","acknowledgement":"We thank Celeste Brennecka for editing and Michal Reichman-Fried for critical comments on the manuscript. We thank Ursula Jordan, Esther Messerschmidt, and Ines Sandbote for technical assistance. This work was supported by funding from the University of Münster (K.J.W., K.T., E.R., A.G., T.G.-T., J.S., and M.G.), the Max Planck Institute for Molecular Biomedicine (D.Z.), the German Research Foundation grant CRU 326 (P2) RA863/12-2 (E.R.), Baylor University (K.H. and D.R.), and the National Institutes of Health grant R35 GM 134910 (D.R.). We thank the referees for insightful comments that helped improve the manuscript.","department":[{"_id":"Bio"}],"article_type":"original","title":"Spatial organization and function of RNA molecules within phase-separated condensates in zebrafish are controlled by Dnd1","oa":1,"publication_status":"published","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"09","_id":"14781"},{"acknowledgement":"A.S . received an award from European Research Council (https://erc.europa.eu, “NEPA\"\r\n802960), and an award from the Royal Society (https://royalsociety.org, UF160266). L. H.-K.\r\nreceived an award from the Biotechnology and Biological Sciences Research Council (https://\r\nwww.ukri.org/councils/bbsrc/). E. L. received an award from the University College London (https://www.ucl.ac.uk/biophysics/news/2022/feb/applications-biop-brian-duff-and-ipls-summerundergraduate-studentships-now-open, Brian Duff Undergraduate Summer Research Studentship). B.B. and A.S. received an award from Volkswagen Foundation https://www.volkswagenstiftung.de/en/foundation, Az 96727), and an award from Medical Research Council (https://www.ukri.org/councils/mrc, MC_CF1226). A. R. received an\r\naward from the Swiss National Fund for Research (https://www.snf.ch/en, 31003A_130520,\r\n31003A_149975, and 31003A_173087) and an award from the European Research Council\r\nConsolidator (https://erc.europa.eu, 311536). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","department":[{"_id":"AnSa"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"12152","month":"10","article_type":"original","title":"Modelling membrane reshaping by staged polymerization of ESCRT-III filaments","oa":1,"related_material":{"link":[{"url":"https://github.com/sharonJXY/3-filament-model","relation":"software"}]},"publication_status":"published","has_accepted_license":"1","day":"17","citation":{"short":"X. Jiang, L. Harker-Kirschneck, C.E. Vanhille-Campos, A.-K. Pfitzner, E. Lominadze, A. Roux, B. Baum, A. Šarić, PLOS Computational Biology 18 (2022).","ama":"Jiang X, Harker-Kirschneck L, Vanhille-Campos CE, et al. Modelling membrane reshaping by staged polymerization of ESCRT-III filaments. <i>PLOS Computational Biology</i>. 2022;18(10). doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1010586\">10.1371/journal.pcbi.1010586</a>","chicago":"Jiang, Xiuyun, Lena Harker-Kirschneck, Christian Eduardo Vanhille-Campos, Anna-Katharina Pfitzner, Elene Lominadze, Aurélien Roux, Buzz Baum, and Anđela Šarić. “Modelling Membrane Reshaping by Staged Polymerization of ESCRT-III Filaments.” <i>PLOS Computational Biology</i>. Public Library of Science, 2022. <a href=\"https://doi.org/10.1371/journal.pcbi.1010586\">https://doi.org/10.1371/journal.pcbi.1010586</a>.","ista":"Jiang X, Harker-Kirschneck L, Vanhille-Campos CE, Pfitzner A-K, Lominadze E, Roux A, Baum B, Šarić A. 2022. Modelling membrane reshaping by staged polymerization of ESCRT-III filaments. PLOS Computational Biology. 18(10), e1010586.","apa":"Jiang, X., Harker-Kirschneck, L., Vanhille-Campos, C. E., Pfitzner, A.-K., Lominadze, E., Roux, A., … Šarić, A. (2022). Modelling membrane reshaping by staged polymerization of ESCRT-III filaments. <i>PLOS Computational Biology</i>. Public Library of Science. <a href=\"https://doi.org/10.1371/journal.pcbi.1010586\">https://doi.org/10.1371/journal.pcbi.1010586</a>","mla":"Jiang, Xiuyun, et al. “Modelling Membrane Reshaping by Staged Polymerization of ESCRT-III Filaments.” <i>PLOS Computational Biology</i>, vol. 18, no. 10, e1010586, Public Library of Science, 2022, doi:<a href=\"https://doi.org/10.1371/journal.pcbi.1010586\">10.1371/journal.pcbi.1010586</a>.","ieee":"X. Jiang <i>et al.</i>, “Modelling membrane reshaping by staged polymerization of ESCRT-III filaments,” <i>PLOS Computational Biology</i>, vol. 18, no. 10. Public Library of Science, 2022."},"intvolume":"        18","keyword":["Computational Theory and Mathematics","Cellular and Molecular Neuroscience","Genetics","Molecular Biology","Ecology","Modeling and Simulation","Ecology","Evolution","Behavior and Systematics"],"ec_funded":1,"abstract":[{"lang":"eng","text":"ESCRT-III filaments are composite cytoskeletal polymers that can constrict and cut cell membranes from the inside of the membrane neck. Membrane-bound ESCRT-III filaments undergo a series of dramatic composition and geometry changes in the presence of an ATP-consuming Vps4 enzyme, which causes stepwise changes in the membrane morphology. We set out to understand the physical mechanisms involved in translating the changes in ESCRT-III polymer composition into membrane deformation. We have built a coarse-grained model in which ESCRT-III polymers of different geometries and mechanical properties are allowed to copolymerise and bind to a deformable membrane. By modelling ATP-driven stepwise depolymerisation of specific polymers, we identify mechanical regimes in which changes in filament composition trigger the associated membrane transition from a flat to a buckled state, and then to a tubule state that eventually undergoes scission to release a small cargo-loaded vesicle. We then characterise how the location and kinetics of polymer loss affects the extent of membrane deformation and the efficiency of membrane neck scission. Our results identify the near-minimal mechanical conditions for the operation of shape-shifting composite polymers that sever membrane necks."}],"article_number":"e1010586","status":"public","date_published":"2022-10-17T00:00:00Z","external_id":{"isi":["000924885500005"]},"oa_version":"Published Version","ddc":["570"],"author":[{"last_name":"Jiang","full_name":"Jiang, Xiuyun","first_name":"Xiuyun"},{"last_name":"Harker-Kirschneck","full_name":"Harker-Kirschneck, Lena","first_name":"Lena"},{"id":"3adeca52-9313-11ed-b1ac-c170b2505714","last_name":"Vanhille-Campos","first_name":"Christian Eduardo","full_name":"Vanhille-Campos, Christian Eduardo"},{"last_name":"Pfitzner","first_name":"Anna-Katharina","full_name":"Pfitzner, Anna-Katharina"},{"first_name":"Elene","full_name":"Lominadze, Elene","last_name":"Lominadze"},{"first_name":"Aurélien","full_name":"Roux, Aurélien","last_name":"Roux"},{"last_name":"Baum","first_name":"Buzz","full_name":"Baum, Buzz"},{"id":"bf63d406-f056-11eb-b41d-f263a6566d8b","orcid":"0000-0002-7854-2139","full_name":"Šarić, Anđela","first_name":"Anđela","last_name":"Šarić"}],"publication":"PLOS Computational Biology","issue":"10","publisher":"Public Library of Science","doi":"10.1371/journal.pcbi.1010586","file_date_updated":"2023-01-24T10:45:01Z","type":"journal_article","language":[{"iso":"eng"}],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"article_processing_charge":"No","scopus_import":"1","publication_identifier":{"issn":["1553-7358"]},"date_updated":"2023-08-04T09:03:21Z","project":[{"call_identifier":"H2020","name":"Non-Equilibrium Protein Assembly: from Building Blocks to Biological Machines","grant_number":"802960","_id":"eba2549b-77a9-11ec-83b8-a81e493eae4e"},{"_id":"eba0f67c-77a9-11ec-83b8-cc8501b3e222","name":"The evolution of trafficking: from archaea to eukaryotes","grant_number":"96752"}],"quality_controlled":"1","year":"2022","date_created":"2023-01-12T12:08:10Z","volume":18,"isi":1,"file":[{"relation":"main_file","checksum":"bada6a7865e470cf42bbdfa67dd471d2","file_size":2641067,"creator":"dernst","file_name":"2022_PLoSCompBio_Jiang.pdf","file_id":"12359","content_type":"application/pdf","date_created":"2023-01-24T10:45:01Z","access_level":"open_access","date_updated":"2023-01-24T10:45:01Z","success":1}]},{"abstract":[{"text":"Models of transcriptional regulation that assume equilibrium binding of transcription factors have been less successful at predicting gene expression from sequence in eukaryotes than in bacteria. This could be due to the non-equilibrium nature of eukaryotic regulation. Unfortunately, the space of possible non-equilibrium mechanisms is vast and predominantly uninteresting. The key question is therefore how this space can be navigated efficiently, to focus on mechanisms and models that are biologically relevant. In this review, we advocate for the normative role of theory—theory that prescribes rather than just describes—in providing such a focus. Theory should expand its remit beyond inferring mechanistic models from data, towards identifying non-equilibrium gene regulatory schemes that may have been evolutionarily selected, despite their energy consumption, because they are precise, reliable, fast, or otherwise outperform regulation at equilibrium. We illustrate our reasoning by toy examples for which we provide simulation code.","lang":"eng"}],"status":"public","article_number":"100435","intvolume":"        31","citation":{"short":"B. Zoller, T. Gregor, G. Tkačik, Current Opinion in Systems Biology 31 (2022).","ama":"Zoller B, Gregor T, Tkačik G. Eukaryotic gene regulation at equilibrium, or non? <i>Current Opinion in Systems Biology</i>. 2022;31(9). doi:<a href=\"https://doi.org/10.1016/j.coisb.2022.100435\">10.1016/j.coisb.2022.100435</a>","apa":"Zoller, B., Gregor, T., &#38; Tkačik, G. (2022). Eukaryotic gene regulation at equilibrium, or non? <i>Current Opinion in Systems Biology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.coisb.2022.100435\">https://doi.org/10.1016/j.coisb.2022.100435</a>","ista":"Zoller B, Gregor T, Tkačik G. 2022. Eukaryotic gene regulation at equilibrium, or non? Current Opinion in Systems Biology. 31(9), 100435.","chicago":"Zoller, Benjamin, Thomas Gregor, and Gašper Tkačik. “Eukaryotic Gene Regulation at Equilibrium, or Non?” <i>Current Opinion in Systems Biology</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.coisb.2022.100435\">https://doi.org/10.1016/j.coisb.2022.100435</a>.","mla":"Zoller, Benjamin, et al. “Eukaryotic Gene Regulation at Equilibrium, or Non?” <i>Current Opinion in Systems Biology</i>, vol. 31, no. 9, 100435, Elsevier, 2022, doi:<a href=\"https://doi.org/10.1016/j.coisb.2022.100435\">10.1016/j.coisb.2022.100435</a>.","ieee":"B. Zoller, T. Gregor, and G. Tkačik, “Eukaryotic gene regulation at equilibrium, or non?,” <i>Current Opinion in Systems Biology</i>, vol. 31, no. 9. Elsevier, 2022."},"keyword":["Applied Mathematics","Computer Science Applications","Drug Discovery","General Biochemistry","Genetics and Molecular Biology","Modeling and Simulation"],"has_accepted_license":"1","day":"01","article_type":"original","publication_status":"published","oa":1,"title":"Eukaryotic gene regulation at equilibrium, or non?","month":"09","_id":"12156","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","acknowledgement":"This work was supported through the Center for the Physics of Biological Function (PHYe1734030) and by National Institutes of Health Grants R01GM097275 and U01DK127429 (TG). GT acknowledges the support of the Austrian Science Fund grant FWF P28844 and the Human Frontiers Science Program. ","department":[{"_id":"GaTk"}],"file":[{"relation":"main_file","checksum":"97ef01e0cc60cdc84f45640a0f248fb0","file_size":2214944,"creator":"dernst","file_name":"2022_CurrentBiology_Zoller.pdf","date_created":"2023-01-24T12:14:10Z","file_id":"12362","content_type":"application/pdf","access_level":"open_access","date_updated":"2023-01-24T12:14:10Z","success":1}],"volume":31,"project":[{"_id":"254E9036-B435-11E9-9278-68D0E5697425","grant_number":"P28844-B27","name":"Biophysics of information processing in gene regulation","call_identifier":"FWF"}],"date_updated":"2023-02-13T09:20:34Z","year":"2022","date_created":"2023-01-12T12:08:51Z","quality_controlled":"1","scopus_import":"1","publication_identifier":{"issn":["2452-3100"]},"article_processing_charge":"Yes (via OA deal)","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"},"type":"journal_article","file_date_updated":"2023-01-24T12:14:10Z","language":[{"iso":"eng"}],"publisher":"Elsevier","doi":"10.1016/j.coisb.2022.100435","author":[{"first_name":"Benjamin","full_name":"Zoller, Benjamin","last_name":"Zoller"},{"last_name":"Gregor","first_name":"Thomas","full_name":"Gregor, Thomas"},{"id":"3D494DCA-F248-11E8-B48F-1D18A9856A87","orcid":"1","last_name":"Tkačik","first_name":"Gašper","full_name":"Tkačik, Gašper"}],"ddc":["570"],"issue":"9","publication":"Current Opinion in Systems Biology","date_published":"2022-09-01T00:00:00Z","oa_version":"Published Version"},{"oa":1,"title":"Polygenic adaptation after a sudden change in environment","publication_status":"published","article_type":"original","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","month":"09","_id":"12157","acknowledgement":"We thank Guy Amster, Jeremy Berg, Nick Barton, Yuval Simons and Molly Przeworski for many helpful discussions, and Jeremy Berg, Graham Coop, Joachim Hermisson, Guillaume Martin, Will Milligan, Peter Ralph, Yuval Simons, Leo Speidel and Molly Przeworski for comments on the manuscript.\r\nNational Institutes of Health GM115889 Laura Katharine Hayward Guy Sella \r\nNational Institutes of Health GM121372 Laura Katharine Hayward","department":[{"_id":"NiBa"}],"article_number":"66697","status":"public","abstract":[{"text":"Polygenic adaptation is thought to be ubiquitous, yet remains poorly understood. Here, we model this process analytically, in the plausible setting of a highly polygenic, quantitative trait that experiences a sudden shift in the fitness optimum. We show how the mean phenotype changes over time, depending on the effect sizes of loci that contribute to variance in the trait, and characterize the allele dynamics at these loci. Notably, we describe the two phases of the allele dynamics: The first is a rapid phase, in which directional selection introduces small frequency differences between alleles whose effects are aligned with or opposed to the shift, ultimately leading to small differences in their probability of fixation during a second, longer phase, governed by stabilizing selection. As we discuss, key results should hold in more general settings and have important implications for efforts to identify the genetic basis of adaptation in humans and other species.","lang":"eng"}],"keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"intvolume":"        11","citation":{"apa":"Hayward, L., &#38; Sella, G. (2022). Polygenic adaptation after a sudden change in environment. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.66697\">https://doi.org/10.7554/elife.66697</a>","chicago":"Hayward, Laura, and Guy Sella. “Polygenic Adaptation after a Sudden Change in Environment.” <i>ELife</i>. eLife Sciences Publications, 2022. <a href=\"https://doi.org/10.7554/elife.66697\">https://doi.org/10.7554/elife.66697</a>.","ista":"Hayward L, Sella G. 2022. Polygenic adaptation after a sudden change in environment. eLife. 11, 66697.","mla":"Hayward, Laura, and Guy Sella. “Polygenic Adaptation after a Sudden Change in Environment.” <i>ELife</i>, vol. 11, 66697, eLife Sciences Publications, 2022, doi:<a href=\"https://doi.org/10.7554/elife.66697\">10.7554/elife.66697</a>.","ieee":"L. Hayward and G. Sella, “Polygenic adaptation after a sudden change in environment,” <i>eLife</i>, vol. 11. eLife Sciences Publications, 2022.","short":"L. Hayward, G. Sella, ELife 11 (2022).","ama":"Hayward L, Sella G. Polygenic adaptation after a sudden change in environment. <i>eLife</i>. 2022;11. doi:<a href=\"https://doi.org/10.7554/elife.66697\">10.7554/elife.66697</a>"},"day":"26","has_accepted_license":"1","language":[{"iso":"eng"}],"file_date_updated":"2023-01-24T12:21:32Z","type":"journal_article","doi":"10.7554/elife.66697","publisher":"eLife Sciences Publications","publication":"eLife","ddc":["570"],"author":[{"id":"fc885ee5-24bf-11eb-ad7b-bcc5104c0c1b","full_name":"Hayward, Laura","first_name":"Laura","last_name":"Hayward"},{"first_name":"Guy","full_name":"Sella, Guy","last_name":"Sella"}],"oa_version":"Published Version","external_id":{"isi":["000890735600001"]},"date_published":"2022-09-26T00:00:00Z","volume":11,"isi":1,"file":[{"creator":"dernst","file_size":18935612,"checksum":"28de155b231ac1c8d4501c98b2fb359a","relation":"main_file","access_level":"open_access","success":1,"date_updated":"2023-01-24T12:21:32Z","content_type":"application/pdf","date_created":"2023-01-24T12:21:32Z","file_id":"12363","file_name":"2022_eLife_Hayward.pdf"}],"quality_controlled":"1","year":"2022","date_created":"2023-01-12T12:09:00Z","date_updated":"2023-08-04T09:04:58Z","publication_identifier":{"eissn":["2050-084X"]},"scopus_import":"1","article_processing_charge":"No","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)"}}]