[{"intvolume":" 13","main_file_link":[{"url":"https://doi.org/10.7554/eLife.68993","open_access":"1"}],"publisher":"eLife Sciences Publications","type":"journal_article","quality_controlled":"1","language":[{"iso":"eng"}],"department":[{"_id":"JiFr"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_published":"2024-02-21T00:00:00Z","date_created":"2024-02-27T07:10:11Z","publication":"eLife","date_updated":"2024-02-28T12:29:43Z","article_type":"original","oa":1,"year":"2024","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"has_accepted_license":"1","article_processing_charge":"Yes","volume":13,"day":"21","citation":{"mla":"Adamowski, Maciek, et al. “Developmental Patterning Function of GNOM ARF-GEF Mediated from the Cell Periphery.” ELife, vol. 13, eLife Sciences Publications, 2024, doi:10.7554/elife.68993.","chicago":"Adamowski, Maciek, Ivana Matijevic, and Jiří Friml. “Developmental Patterning Function of GNOM ARF-GEF Mediated from the Cell Periphery.” ELife. eLife Sciences Publications, 2024. https://doi.org/10.7554/elife.68993.","short":"M. Adamowski, I. Matijevic, J. Friml, ELife 13 (2024).","ama":"Adamowski M, Matijevic I, Friml J. Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery. eLife. 2024;13. doi:10.7554/elife.68993","ista":"Adamowski M, Matijevic I, Friml J. 2024. Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery. eLife. 13.","apa":"Adamowski, M., Matijevic, I., & Friml, J. (2024). Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.68993","ieee":"M. Adamowski, I. Matijevic, and J. Friml, “Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery,” eLife, vol. 13. eLife Sciences Publications, 2024."},"ddc":["580"],"month":"02","license":"https://creativecommons.org/licenses/by/4.0/","oa_version":"Published Version","publication_identifier":{"issn":["2050-084X"]},"project":[{"_id":"261099A6-B435-11E9-9278-68D0E5697425","grant_number":"742985","name":"Tracing Evolution of Auxin Transport and Polarity in Plants","call_identifier":"H2020"},{"grant_number":"I03630","_id":"26538374-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Molecular mechanisms of endocytic cargo recognition in plants"}],"publication_status":"epub_ahead","status":"public","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","ec_funded":1,"author":[{"orcid":"0000-0001-6463-5257","first_name":"Maciek","id":"45F536D2-F248-11E8-B48F-1D18A9856A87","last_name":"Adamowski","full_name":"Adamowski, Maciek"},{"full_name":"Matijevic, Ivana","last_name":"Matijevic","id":"83c17ce3-15b2-11ec-abd3-f486545870bd","first_name":"Ivana"},{"id":"4159519E-F248-11E8-B48F-1D18A9856A87","first_name":"Jiří","full_name":"Friml, Jiří","last_name":"Friml","orcid":"0000-0002-8302-7596"}],"title":"Developmental patterning function of GNOM ARF-GEF mediated from the cell periphery","_id":"15033","abstract":[{"lang":"eng","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 gn knockouts. The functional GN mutant variant GNfewerroots, 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."}],"doi":"10.7554/elife.68993"},{"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"volume":5,"article_processing_charge":"No","day":"08","citation":{"mla":"Amberg, Nicole, et al. “Protocol for Sorting Cells from Mouse Brains Labeled with Mosaic Analysis with Double Markers by Flow Cytometry.” STAR Protocols, vol. 5, no. 1, 102771, Elsevier, 2023, doi:10.1016/j.xpro.2023.102771.","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.” STAR Protocols. Elsevier, 2023. https://doi.org/10.1016/j.xpro.2023.102771.","apa":"Amberg, N., Cheung, G. T., & Hippenmeyer, S. (2023). Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry. STAR Protocols. Elsevier. https://doi.org/10.1016/j.xpro.2023.102771","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,” STAR Protocols, vol. 5, no. 1. Elsevier, 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. STAR Protocols. 2023;5(1). doi:10.1016/j.xpro.2023.102771","short":"N. Amberg, G.T. Cheung, S. Hippenmeyer, STAR Protocols 5 (2023).","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."},"ddc":["570"],"pmid":1,"month":"12","oa_version":"Submitted Version","publication_identifier":{"issn":["2666-1667"]},"project":[{"call_identifier":"FWF","name":"Role of Eed in neural stem cell lineage progression","_id":"268F8446-B435-11E9-9278-68D0E5697425","grant_number":"T0101031"},{"name":"ISTplus - Postdoctoral Fellowships","call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411"},{"name":"Molecular Mechanisms of Neural Stem Cell Lineage Progression","_id":"059F6AB4-7A3F-11EA-A408-12923DDC885E","grant_number":"F07805"},{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","call_identifier":"H2020","grant_number":"725780","_id":"260018B0-B435-11E9-9278-68D0E5697425"}],"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.","publication_status":"epub_ahead","status":"public","ec_funded":1,"author":[{"orcid":"0000-0002-3183-8207","full_name":"Amberg, Nicole","last_name":"Amberg","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","first_name":"Nicole"},{"orcid":"0000-0001-8457-2572","id":"471195F6-F248-11E8-B48F-1D18A9856A87","first_name":"Giselle T","full_name":"Cheung, Giselle T","last_name":"Cheung"},{"orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon"}],"title":"Protocol for sorting cells from mouse brains labeled with mosaic analysis with double markers by flow cytometry","_id":"14683","issue":"1","abstract":[{"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","lang":"eng"}],"doi":"10.1016/j.xpro.2023.102771","intvolume":" 5","main_file_link":[{"url":"https://doi.org/10.1016/j.xpro.2023.102771","open_access":"1"}],"publisher":"Elsevier","type":"journal_article","quality_controlled":"1","language":[{"iso":"eng"}],"department":[{"_id":"SiHi"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","external_id":{"pmid":["38070137"]},"date_published":"2023-12-08T00:00:00Z","scopus_import":"1","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"date_created":"2023-12-13T11:48:05Z","publication":"STAR Protocols","date_updated":"2023-12-18T08:06:14Z","article_type":"review","article_number":"102771","oa":1,"year":"2023","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Neuroscience"]},{"main_file_link":[{"url":"https://doi.org/10.1126/sciimmunol.adc9584","open_access":"1"}],"intvolume":" 8","publisher":"American Association for the Advancement of Science","language":[{"iso":"eng"}],"type":"journal_article","quality_controlled":"1","isi":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"MiSi"},{"_id":"EdHa"},{"_id":"NanoFab"}],"scopus_import":"1","date_created":"2023-09-06T08:07:51Z","date_published":"2023-09-01T00:00:00Z","external_id":{"isi":["001062110600003"],"pmid":["37656776"]},"date_updated":"2023-12-21T14:30:01Z","publication":"Science Immunology","article_type":"original","article_number":"adc9584","related_material":{"record":[{"id":"14279","status":"public","relation":"research_data"},{"relation":"dissertation_contains","status":"public","id":"14697"}]},"oa":1,"keyword":["General Medicine","Immunology"],"year":"2023","article_processing_charge":"No","volume":8,"month":"09","pmid":1,"day":"01","citation":{"chicago":"Alanko, Jonna H, Mehmet C Ucar, Nikola Canigova, Julian A Stopp, Jan Schwarz, Jack Merrin, Edouard B Hannezo, and Michael K Sixt. “CCR7 Acts as Both a Sensor and a Sink for CCL19 to Coordinate Collective Leukocyte Migration.” Science Immunology. American Association for the Advancement of Science, 2023. https://doi.org/10.1126/sciimmunol.adc9584.","mla":"Alanko, Jonna H., et al. “CCR7 Acts as Both a Sensor and a Sink for CCL19 to Coordinate Collective Leukocyte Migration.” Science Immunology, vol. 8, no. 87, adc9584, American Association for the Advancement of Science, 2023, doi:10.1126/sciimmunol.adc9584.","ama":"Alanko JH, Ucar MC, Canigova N, et al. CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration. Science Immunology. 2023;8(87). doi:10.1126/sciimmunol.adc9584","short":"J.H. Alanko, M.C. Ucar, N. Canigova, J.A. Stopp, J. Schwarz, J. Merrin, E.B. Hannezo, M.K. Sixt, Science Immunology 8 (2023).","ista":"Alanko JH, Ucar MC, Canigova N, Stopp JA, Schwarz J, Merrin J, Hannezo EB, Sixt MK. 2023. CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration. Science Immunology. 8(87), adc9584.","ieee":"J. H. Alanko et al., “CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration,” Science Immunology, vol. 8, no. 87. American Association for the Advancement of Science, 2023.","apa":"Alanko, J. H., Ucar, M. C., Canigova, N., Stopp, J. A., Schwarz, J., Merrin, J., … Sixt, M. K. (2023). CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration. Science Immunology. American Association for the Advancement of Science. https://doi.org/10.1126/sciimmunol.adc9584"},"oa_version":"Published Version","project":[{"call_identifier":"H2020","name":"Cellular navigation along spatial gradients","grant_number":"724373","_id":"25FE9508-B435-11E9-9278-68D0E5697425"},{"grant_number":"851288","_id":"05943252-7A3F-11EA-A408-12923DDC885E","call_identifier":"H2020","name":"Design Principles of Branching Morphogenesis"},{"grant_number":"W01250-B20","_id":"265E2996-B435-11E9-9278-68D0E5697425","name":"Nano-Analytics of Cellular Systems","call_identifier":"FWF"},{"name":"ISTplus - Postdoctoral Fellowships","call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411"}],"publication_identifier":{"issn":["2470-9468"]},"ec_funded":1,"acknowledgement":"We thank I. de Vries and the Scientific Service Units (Life Sciences, Bioimaging, Nanofabrication, Preclinical and Miba Machine Shop) of the Institute of Science and Technology Austria for excellent support, as well as all the rotation students assisting in the laboratory work (B. Zens, H. Schön, and D. Babic).\r\nThis work was supported by grants from the European Research Council under the European Union’s Horizon 2020 research to M.S. (grant agreement no. 724373) and to E.H. (grant agreement no. 851288), and a grant by the Austrian Science Fund (DK Nanocell W1250-B20) to M.S. J.A. was supported by the Jenny and Antti Wihuri Foundation and Research Council of Finland's Flagship Programme InFLAMES (decision number: 357910). M.C.U. was supported by the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement no. 754411.","publication_status":"published","status":"public","_id":"14274","author":[{"first_name":"Jonna H","id":"2CC12E8C-F248-11E8-B48F-1D18A9856A87","last_name":"Alanko","full_name":"Alanko, Jonna H","orcid":"0000-0002-7698-3061"},{"orcid":"0000-0003-0506-4217","first_name":"Mehmet C","id":"50B2A802-6007-11E9-A42B-EB23E6697425","last_name":"Ucar","full_name":"Ucar, Mehmet C"},{"last_name":"Canigova","full_name":"Canigova, Nikola","first_name":"Nikola","id":"3795523E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-8518-5926"},{"last_name":"Stopp","full_name":"Stopp, Julian A","first_name":"Julian A","id":"489E3F00-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Schwarz","full_name":"Schwarz, Jan","first_name":"Jan","id":"346C1EC6-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Jack","id":"4515C308-F248-11E8-B48F-1D18A9856A87","last_name":"Merrin","full_name":"Merrin, Jack","orcid":"0000-0001-5145-4609"},{"orcid":"0000-0001-6005-1561","full_name":"Hannezo, Edouard B","last_name":"Hannezo","id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","first_name":"Edouard B"},{"orcid":"0000-0002-6620-9179","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","full_name":"Sixt, Michael K","last_name":"Sixt"}],"title":"CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration","doi":"10.1126/sciimmunol.adc9584","issue":"87","abstract":[{"lang":"eng","text":"Immune responses rely on the rapid and coordinated migration of leukocytes. Whereas it is well established that single-cell migration is often guided by gradients of chemokines and other chemoattractants, it remains poorly understood how these gradients are generated, maintained, and modulated. By combining experimental data with theory on leukocyte chemotaxis guided by the G protein–coupled receptor (GPCR) CCR7, we demonstrate that in addition to its role as the sensory receptor that steers migration, CCR7 also acts as a generator and a modulator of chemotactic gradients. Upon exposure to the CCR7 ligand CCL19, dendritic cells (DCs) effectively internalize the receptor and ligand as part of the canonical GPCR desensitization response. We show that CCR7 internalization also acts as an effective sink for the chemoattractant, dynamically shaping the spatiotemporal distribution of the chemokine. This mechanism drives complex collective migration patterns, enabling DCs to create or sharpen chemotactic gradients. We further show that these self-generated gradients can sustain the long-range guidance of DCs, adapt collective migration patterns to the size and geometry of the environment, and provide a guidance cue for other comigrating cells. Such a dual role of CCR7 as a GPCR that both senses and consumes its ligand can thus provide a novel mode of cellular self-organization."}]},{"external_id":{"pmid":["35241807"],"isi":["000763891900001"]},"date_published":"2022-08-01T00:00:00Z","scopus_import":"1","date_created":"2022-03-04T04:33:49Z","department":[{"_id":"CaGu"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","isi":1,"type":"journal_article","language":[{"iso":"eng"}],"quality_controlled":"1","intvolume":" 20","publisher":"Springer Nature","year":"2022","keyword":["General Immunology and Microbiology","Microbiology","Infectious Diseases"],"article_type":"review","page":"478-490","publication":"Nature Reviews Microbiology","date_updated":"2023-08-02T14:41:44Z","oa_version":"None","day":"01","citation":{"apa":"Römhild, R., Bollenbach, M. T., & Andersson, D. I. (2022). The physiology and genetics of bacterial responses to antibiotic combinations. Nature Reviews Microbiology. Springer Nature. https://doi.org/10.1038/s41579-022-00700-5","ieee":"R. Römhild, M. T. Bollenbach, and D. I. Andersson, “The physiology and genetics of bacterial responses to antibiotic combinations,” Nature Reviews Microbiology, vol. 20. Springer Nature, pp. 478–490, 2022.","ama":"Römhild R, Bollenbach MT, Andersson DI. The physiology and genetics of bacterial responses to antibiotic combinations. Nature Reviews Microbiology. 2022;20:478-490. doi:10.1038/s41579-022-00700-5","ista":"Römhild R, Bollenbach MT, Andersson DI. 2022. The physiology and genetics of bacterial responses to antibiotic combinations. Nature Reviews Microbiology. 20, 478–490.","short":"R. Römhild, M.T. Bollenbach, D.I. Andersson, Nature Reviews Microbiology 20 (2022) 478–490.","chicago":"Römhild, Roderich, Mark Tobias Bollenbach, and Dan I. Andersson. “The Physiology and Genetics of Bacterial Responses to Antibiotic Combinations.” Nature Reviews Microbiology. Springer Nature, 2022. https://doi.org/10.1038/s41579-022-00700-5.","mla":"Römhild, Roderich, et al. “The Physiology and Genetics of Bacterial Responses to Antibiotic Combinations.” Nature Reviews Microbiology, vol. 20, Springer Nature, 2022, pp. 478–90, doi:10.1038/s41579-022-00700-5."},"pmid":1,"month":"08","article_processing_charge":"No","volume":20,"abstract":[{"lang":"eng","text":"Several promising strategies based on combining or cycling different antibiotics have been proposed to increase efficacy and counteract resistance evolution, but we still lack a deep understanding of the physiological responses and genetic mechanisms that underlie antibiotic interactions and the clinical applicability of these strategies. In antibiotic-exposed bacteria, the combined effects of physiological stress responses and emerging resistance mutations (occurring at different time scales) generate complex and often unpredictable dynamics. In this Review, we present our current understanding of bacterial cell physiology and genetics of responses to antibiotics. We emphasize recently discovered mechanisms of synergistic and antagonistic drug interactions, hysteresis in temporal interactions between antibiotics that arise from microbial physiology and interactions between antibiotics and resistance mutations that can cause collateral sensitivity or cross-resistance. We discuss possible connections between the different phenomena and indicate relevant research directions. A better and more unified understanding of drug and genetic interactions is likely to advance antibiotic therapy."}],"doi":"10.1038/s41579-022-00700-5","author":[{"id":"68E56E44-62B0-11EA-B963-444F3DDC885E","first_name":"Roderich","full_name":"Römhild, Roderich","last_name":"Römhild","orcid":"0000-0001-9480-5261"},{"orcid":"0000-0003-4398-476X","full_name":"Bollenbach, Mark Tobias","last_name":"Bollenbach","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","first_name":"Mark Tobias"},{"full_name":"Andersson, Dan I.","last_name":"Andersson","first_name":"Dan I."}],"title":"The physiology and genetics of bacterial responses to antibiotic combinations","_id":"10812","acknowledgement":"The authors thank B. Kavčič and H. Schulenburg for constructive feedback on the manuscript.","status":"public","publication_status":"published","publication_identifier":{"eissn":["1740-1534"],"issn":["1740-1526"]}},{"publisher":"Springer Nature","intvolume":" 84","type":"journal_article","quality_controlled":"1","language":[{"iso":"eng"}],"isi":1,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"GradSch"},{"_id":"NiBa"},{"_id":"JaMa"}],"date_created":"2022-06-17T16:16:15Z","scopus_import":"1","date_published":"2022-06-17T00:00:00Z","external_id":{"isi":["000812509800001"]},"date_updated":"2023-08-03T07:20:53Z","publication":"Bulletin of Mathematical Biology","article_number":"74","article_type":"original","related_material":{"link":[{"relation":"erratum","url":"https://doi.org/10.1007/s11538-022-01118-z"}]},"oa":1,"keyword":["Computational Theory and Mathematics","General Agricultural and Biological Sciences","Pharmacology","General Environmental Science","General Biochemistry","Genetics and Molecular Biology","General Mathematics","Immunology","General Neuroscience"],"year":"2022","file":[{"content_type":"application/pdf","checksum":"05a1fe7d10914a00c2bca9b447993a65","access_level":"open_access","date_updated":"2022-06-20T07:51:32Z","success":1,"file_size":463025,"relation":"main_file","creator":"dernst","file_name":"2022_BulletinMathBiology_Saona.pdf","date_created":"2022-06-20T07:51:32Z","file_id":"11455"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"volume":84,"article_processing_charge":"Yes (via OA deal)","has_accepted_license":"1","file_date_updated":"2022-06-20T07:51:32Z","month":"06","ddc":["510","570"],"citation":{"mla":"Saona Urmeneta, Raimundo J., et al. “Relation between the Number of Peaks and the Number of Reciprocal Sign Epistatic Interactions.” Bulletin of Mathematical Biology, vol. 84, no. 8, 74, Springer Nature, 2022, doi:10.1007/s11538-022-01029-z.","chicago":"Saona Urmeneta, Raimundo J, Fyodor Kondrashov, and Kseniia Khudiakova. “Relation between the Number of Peaks and the Number of Reciprocal Sign Epistatic Interactions.” Bulletin of Mathematical Biology. Springer Nature, 2022. https://doi.org/10.1007/s11538-022-01029-z.","short":"R.J. Saona Urmeneta, F. Kondrashov, K. Khudiakova, Bulletin of Mathematical Biology 84 (2022).","ista":"Saona Urmeneta RJ, Kondrashov F, Khudiakova K. 2022. Relation between the number of peaks and the number of reciprocal sign epistatic interactions. Bulletin of Mathematical Biology. 84(8), 74.","ama":"Saona Urmeneta RJ, Kondrashov F, Khudiakova K. Relation between the number of peaks and the number of reciprocal sign epistatic interactions. Bulletin of Mathematical Biology. 2022;84(8). doi:10.1007/s11538-022-01029-z","ieee":"R. J. Saona Urmeneta, F. Kondrashov, and K. Khudiakova, “Relation between the number of peaks and the number of reciprocal sign epistatic interactions,” Bulletin of Mathematical Biology, vol. 84, no. 8. Springer Nature, 2022.","apa":"Saona Urmeneta, R. J., Kondrashov, F., & Khudiakova, K. (2022). Relation between the number of peaks and the number of reciprocal sign epistatic interactions. Bulletin of Mathematical Biology. Springer Nature. https://doi.org/10.1007/s11538-022-01029-z"},"day":"17","oa_version":"Published Version","project":[{"name":"Characterizing the fitness landscape on population and global scales","call_identifier":"H2020","grant_number":"771209","_id":"26580278-B435-11E9-9278-68D0E5697425"},{"name":"Evolutionary analysis of gene regulation","grant_number":"I05127","_id":"c098eddd-5a5b-11eb-8a69-abe27170a68f"}],"publication_identifier":{"eissn":["1522-9602"],"issn":["0092-8240"]},"ec_funded":1,"acknowledgement":"We are grateful to Herbert Edelsbrunner and Jeferson Zapata for helpful discussions. Open access funding provided by Austrian Science Fund (FWF). Partially supported by the ERC Consolidator (771209–CharFL) and the FWF Austrian Science Fund (I5127-B) grants to FAK.","status":"public","publication_status":"published","_id":"11447","title":"Relation between the number of peaks and the number of reciprocal sign epistatic interactions","author":[{"last_name":"Saona Urmeneta","full_name":"Saona Urmeneta, Raimundo J","first_name":"Raimundo J","id":"BD1DF4C4-D767-11E9-B658-BC13E6697425","orcid":"0000-0001-5103-038X"},{"first_name":"Fyodor","id":"44FDEF62-F248-11E8-B48F-1D18A9856A87","last_name":"Kondrashov","full_name":"Kondrashov, Fyodor","orcid":"0000-0001-8243-4694"},{"orcid":"0000-0002-6246-1465","first_name":"Kseniia","id":"4E6DC800-AE37-11E9-AC72-31CAE5697425","last_name":"Khudiakova","full_name":"Khudiakova, Kseniia"}],"doi":"10.1007/s11538-022-01029-z","abstract":[{"text":"Empirical essays of fitness landscapes suggest that they may be rugged, that is having multiple fitness peaks. Such fitness landscapes, those that have multiple peaks, necessarily have special local structures, called reciprocal sign epistasis (Poelwijk et al. in J Theor Biol 272:141–144, 2011). Here, we investigate the quantitative relationship between the number of fitness peaks and the number of reciprocal sign epistatic interactions. Previously, it has been shown (Poelwijk et al. in J Theor Biol 272:141–144, 2011) that pairwise reciprocal sign epistasis is a necessary but not sufficient condition for the existence of multiple peaks. Applying discrete Morse theory, which to our knowledge has never been used in this context, we extend this result by giving the minimal number of reciprocal sign epistatic interactions required to create a given number of peaks.","lang":"eng"}],"issue":"8"},{"isi":1,"type":"journal_article","language":[{"iso":"eng"}],"quality_controlled":"1","intvolume":" 11","publisher":"eLife Sciences Publications","date_published":"2022-05-05T00:00:00Z","external_id":{"isi":["000799197200001"]},"scopus_import":"1","acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"}],"date_created":"2022-06-18T09:06:59Z","department":[{"_id":"GradSch"},{"_id":"FyKo"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_type":"original","article_number":"75842","publication":"eLife","date_updated":"2023-08-03T07:20:15Z","year":"2022","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"oa":1,"has_accepted_license":"1","article_processing_charge":"No","volume":11,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"file":[{"date_created":"2022-06-20T07:44:19Z","file_id":"11454","creator":"dernst","relation":"main_file","file_size":5297213,"file_name":"2022_eLife_Somermeyer.pdf","content_type":"application/pdf","checksum":"7573c28f44028ab0cc81faef30039e44","access_level":"open_access","date_updated":"2022-06-20T07:44:19Z","success":1}],"oa_version":"Published Version","day":"05","citation":{"chicago":"Gonzalez Somermeyer, Louisa, Aubin Fleiss, Alexander S Mishin, Nina G Bozhanova, Anna A Igolkina, Jens Meiler, Maria-Elisenda Alaball Pujol, Ekaterina V Putintseva, Karen S Sarkisyan, and Fyodor Kondrashov. “Heterogeneity of the GFP Fitness Landscape and Data-Driven Protein Design.” ELife. eLife Sciences Publications, 2022. https://doi.org/10.7554/elife.75842.","mla":"Gonzalez Somermeyer, Louisa, et al. “Heterogeneity of the GFP Fitness Landscape and Data-Driven Protein Design.” ELife, vol. 11, 75842, eLife Sciences Publications, 2022, doi:10.7554/elife.75842.","ista":"Gonzalez Somermeyer L, Fleiss A, Mishin AS, Bozhanova NG, Igolkina AA, Meiler J, Alaball Pujol M-E, Putintseva EV, Sarkisyan KS, Kondrashov F. 2022. Heterogeneity of the GFP fitness landscape and data-driven protein design. eLife. 11, 75842.","short":"L. Gonzalez Somermeyer, A. Fleiss, A.S. Mishin, N.G. Bozhanova, A.A. Igolkina, J. Meiler, M.-E. Alaball Pujol, E.V. Putintseva, K.S. Sarkisyan, F. Kondrashov, ELife 11 (2022).","ama":"Gonzalez Somermeyer L, Fleiss A, Mishin AS, et al. Heterogeneity of the GFP fitness landscape and data-driven protein design. eLife. 2022;11. doi:10.7554/elife.75842","ieee":"L. Gonzalez Somermeyer et al., “Heterogeneity of the GFP fitness landscape and data-driven protein design,” eLife, vol. 11. eLife Sciences Publications, 2022.","apa":"Gonzalez Somermeyer, L., Fleiss, A., Mishin, A. S., Bozhanova, N. G., Igolkina, A. A., Meiler, J., … Kondrashov, F. (2022). Heterogeneity of the GFP fitness landscape and data-driven protein design. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.75842"},"month":"05","file_date_updated":"2022-06-20T07:44:19Z","ddc":["570"],"status":"public","publication_status":"published","acknowledgement":"We thank Ondřej Draganov, Rodrigo Redondo, Bor Kavčič, Mia Juračić and Andrea Pauli for discussion and technical advice. We thank Anita Testa Salmazo for advice on resin protein purification, Dmitry Bolotin and the Milaboratory (milaboratory.com) for access to computing and storage infrastructure, and Josef Houser and Eva Fujdiarova for technical assistance and data interpretation. Core facility Biomolecular Interactions and Crystallization of CEITEC Masaryk University is gratefully acknowledged for the obtaining of the scientific data presented in this paper. This research was supported by the Scientific Service Units (SSU) of IST-Austria\r\nthrough resources provided by the Bioimaging Facility (BIF), and the Life Science Facility (LSF). MiSeq and HiSeq NGS sequencing was performed by the Next Generation Sequencing Facility at Vienna BioCenter Core Facilities (VBCF), member of the Vienna BioCenter (VBC), Austria. FACS was performed at the BioOptics Facility of the Institute of Molecular Pathology (IMP), Austria. We also thank the Biomolecular Crystallography Facility in the Vanderbilt University Center for Structural Biology. We are grateful to Joel M Harp for help with X-ray data collection. This work was supported by the ERC Consolidator grant to FAK (771209—CharFL). KSS acknowledges support by President’s Grant МК–5405.2021.1.4, the Imperial College Research Fellowship and the MRC London Institute of Medical Sciences (UKRI MC-A658-5QEA0).\r\nAF is supported by the Marie Skłodowska-Curie Fellowship (H2020-MSCA-IF-2019, Grant Agreement No. 898203, Project acronym \"FLINDIP\"). Experiments were partially carried out using equipment provided by the Institute of Bioorganic Chemistry of the Russian Academy of Sciences Сore Facility (CKP IBCH). This work was supported by a Russian Science Foundation grant 19-74-10102.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie Grant Agreement No. 665,385.","ec_funded":1,"publication_identifier":{"issn":["2050-084X"]},"project":[{"grant_number":"771209","_id":"26580278-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Characterizing the fitness landscape on population and global scales"},{"grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"International IST Doctoral Program"}],"abstract":[{"lang":"eng","text":"Studies of protein fitness landscapes reveal biophysical constraints guiding protein evolution and empower prediction of functional proteins. However, generalisation of these findings is limited due to scarceness of systematic data on fitness landscapes of proteins with a defined evolutionary relationship. We characterized the fitness peaks of four orthologous fluorescent proteins with a broad range of sequence divergence. While two of the four studied fitness peaks were sharp, the other two were considerably flatter, being almost entirely free of epistatic interactions. Mutationally robust proteins, characterized by a flat fitness peak, were not optimal templates for machine-learning-driven protein design – instead, predictions were more accurate for fragile proteins with epistatic landscapes. Our work paves insights for practical application of fitness landscape heterogeneity in protein engineering."}],"doi":"10.7554/elife.75842","author":[{"first_name":"Louisa","id":"4720D23C-F248-11E8-B48F-1D18A9856A87","last_name":"Gonzalez Somermeyer","full_name":"Gonzalez Somermeyer, Louisa","orcid":"0000-0001-9139-5383"},{"first_name":"Aubin","full_name":"Fleiss, Aubin","last_name":"Fleiss"},{"last_name":"Mishin","full_name":"Mishin, Alexander S","first_name":"Alexander S"},{"first_name":"Nina G","last_name":"Bozhanova","full_name":"Bozhanova, Nina G"},{"last_name":"Igolkina","full_name":"Igolkina, Anna A","first_name":"Anna A"},{"first_name":"Jens","full_name":"Meiler, Jens","last_name":"Meiler"},{"last_name":"Alaball Pujol","full_name":"Alaball Pujol, Maria-Elisenda","first_name":"Maria-Elisenda"},{"first_name":"Ekaterina V","last_name":"Putintseva","full_name":"Putintseva, Ekaterina V"},{"last_name":"Sarkisyan","full_name":"Sarkisyan, Karen S","first_name":"Karen S"},{"first_name":"Fyodor","id":"44FDEF62-F248-11E8-B48F-1D18A9856A87","last_name":"Kondrashov","full_name":"Kondrashov, Fyodor","orcid":"0000-0001-8243-4694"}],"title":"Heterogeneity of the GFP fitness landscape and data-driven protein design","_id":"11448"},{"abstract":[{"text":"With more than 80 members worldwide, the Orthobunyavirus genus in the Peribunyaviridae family is a large genus of enveloped RNA viruses, many of which are emerging pathogens in humans and livestock. How orthobunyaviruses (OBVs) penetrate and infect mammalian host cells remains poorly characterized. Here, we investigated the entry mechanisms of the OBV Germiston (GERV). Viral particles were visualized by cryo-electron microscopy and appeared roughly spherical with an average diameter of 98 nm. Labeling of the virus with fluorescent dyes did not adversely affect its infectivity and allowed the monitoring of single particles in fixed and live cells. Using this approach, we found that endocytic internalization of bound viruses was asynchronous and occurred within 30-40 min. The virus entered Rab5a+ early endosomes and, subsequently, late endosomal vacuoles containing Rab7a but not LAMP-1. Infectious entry did not require proteolytic cleavage, and endosomal acidification was sufficient and necessary for viral fusion. Acid-activated penetration began 15-25 min after initiation of virus internalization and relied on maturation of early endosomes to late endosomes. The optimal pH for viral membrane fusion was slightly below 6.0, and penetration was hampered when the potassium influx was abolished. Overall, our study provides real-time visualization of GERV entry into host cells and demonstrates the importance of late endosomal maturation in facilitating OBV penetration.","lang":"eng"}],"issue":"5","doi":"10.1128/jvi.02146-21","title":"The Orthobunyavirus Germiston enters host cells from late endosomes","author":[{"full_name":"Windhaber, Stefan","last_name":"Windhaber","first_name":"Stefan"},{"last_name":"Xin","full_name":"Xin, Qilin","first_name":"Qilin"},{"full_name":"Uckeley, Zina M.","last_name":"Uckeley","first_name":"Zina M."},{"last_name":"Koch","full_name":"Koch, Jana","first_name":"Jana"},{"full_name":"Obr, Martin","last_name":"Obr","id":"4741CA5A-F248-11E8-B48F-1D18A9856A87","first_name":"Martin"},{"first_name":"Céline","full_name":"Garnier, Céline","last_name":"Garnier"},{"full_name":"Luengo-Guyonnot, Catherine","last_name":"Luengo-Guyonnot","first_name":"Catherine"},{"last_name":"Duboeuf","full_name":"Duboeuf, Maëva","first_name":"Maëva"},{"orcid":"0000-0003-4790-8078","first_name":"Florian KM","id":"48AD8942-F248-11E8-B48F-1D18A9856A87","last_name":"Schur","full_name":"Schur, Florian KM"},{"full_name":"Lozach, Pierre-Yves","last_name":"Lozach","first_name":"Pierre-Yves"}],"_id":"10639","acknowledgement":"This work was supported by INRAE starter funds, Project IDEXLYON (University of Lyon) within the Programme Investissements d’Avenir (ANR-16-IDEX-0005), and FINOVIAO14 (Fondation pour l’Université de Lyon), all to P.Y.L. This work was also supported by CellNetworks Research Group funds and Deutsche Forschungsgemeinschaft (DFG) funding (grant numbers LO-2338/1-1 and LO-2338/3-1) awarded to P.Y.L., Austrian Science Fund (FWF) grant P31445 to F.K.M.S., a Chinese Scholarship Council (CSC;no. 201904910701) fellowship to Q.X., and a ministére de l’enseignement supérieur, de la recherche et de l’innovation (MESRI) doctoral thesis grant to M.D.","status":"public","publication_status":"published","publication_identifier":{"eissn":["1098-5514"],"issn":["0022-538X"]},"project":[{"name":"Structural conservation and diversity in retroviral capsid","call_identifier":"FWF","grant_number":"P31445","_id":"26736D6A-B435-11E9-9278-68D0E5697425"}],"oa_version":"Published Version","citation":{"chicago":"Windhaber, Stefan, Qilin Xin, Zina M. Uckeley, Jana Koch, Martin Obr, Céline Garnier, Catherine Luengo-Guyonnot, Maëva Duboeuf, Florian KM Schur, and Pierre-Yves Lozach. “The Orthobunyavirus Germiston Enters Host Cells from Late Endosomes.” Journal of Virology. American Society for Microbiology, 2022. https://doi.org/10.1128/jvi.02146-21.","mla":"Windhaber, Stefan, et al. “The Orthobunyavirus Germiston Enters Host Cells from Late Endosomes.” Journal of Virology, vol. 96, no. 5, e02146-21, American Society for Microbiology, 2022, doi:10.1128/jvi.02146-21.","ama":"Windhaber S, Xin Q, Uckeley ZM, et al. The Orthobunyavirus Germiston enters host cells from late endosomes. Journal of Virology. 2022;96(5). doi:10.1128/jvi.02146-21","ista":"Windhaber S, Xin Q, Uckeley ZM, Koch J, Obr M, Garnier C, Luengo-Guyonnot C, Duboeuf M, Schur FK, Lozach P-Y. 2022. The Orthobunyavirus Germiston enters host cells from late endosomes. Journal of Virology. 96(5), e02146-21.","short":"S. Windhaber, Q. Xin, Z.M. Uckeley, J. Koch, M. Obr, C. Garnier, C. Luengo-Guyonnot, M. Duboeuf, F.K. Schur, P.-Y. Lozach, Journal of Virology 96 (2022).","apa":"Windhaber, S., Xin, Q., Uckeley, Z. M., Koch, J., Obr, M., Garnier, C., … Lozach, P.-Y. (2022). The Orthobunyavirus Germiston enters host cells from late endosomes. Journal of Virology. American Society for Microbiology. https://doi.org/10.1128/jvi.02146-21","ieee":"S. Windhaber et al., “The Orthobunyavirus Germiston enters host cells from late endosomes,” Journal of Virology, vol. 96, no. 5. American Society for Microbiology, 2022."},"day":"01","pmid":1,"month":"03","volume":96,"article_processing_charge":"No","year":"2022","keyword":["virology","insect science","immunology","microbiology"],"oa":1,"article_number":"e02146-21","article_type":"original","publication":"Journal of Virology","date_updated":"2023-08-02T13:52:33Z","external_id":{"pmid":["35019710"],"isi":["000779305000033"]},"date_published":"2022-03-01T00:00:00Z","date_created":"2022-01-18T10:04:18Z","acknowledged_ssus":[{"_id":"EM-Fac"}],"scopus_import":"1","department":[{"_id":"FlSc"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","isi":1,"language":[{"iso":"eng"}],"quality_controlled":"1","type":"journal_article","publisher":"American Society for Microbiology","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8906410","open_access":"1"}],"intvolume":" 96"},{"keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Neuroscience"],"year":"2022","oa":1,"article_number":"101866","article_type":"letter_note","related_material":{"record":[{"status":"public","relation":"other","id":"11478"}]},"date_updated":"2023-11-02T12:21:32Z","publication":"STAR Protocols","date_created":"2023-01-12T11:56:38Z","scopus_import":"1","acknowledged_ssus":[{"_id":"Bio"}],"date_published":"2022-12-16T00:00:00Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"SaSi"},{"_id":"GradSch"}],"type":"journal_article","quality_controlled":"1","language":[{"iso":"eng"}],"publisher":"Elsevier","intvolume":" 3","doi":"10.1016/j.xpro.2022.101866","abstract":[{"text":"To understand how potential gene manipulations affect in vitro microglia, we provide a set of short protocols to evaluate microglia identity and function. We detail steps for immunostaining to determine microglia identity. We describe three functional assays for microglia: phagocytosis, calcium response following ATP stimulation, and cytokine expression upon inflammatory stimuli. We apply these protocols to human induced-pluripotent-stem-cell (hiPSC)-derived microglia, but they can be also applied to other in vitro microglial models including primary mouse microglia.\r\nFor complete details on the use and execution of this protocol, please refer to Bartalska et al. (2022).1","lang":"eng"}],"issue":"4","_id":"12117","title":"Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay","author":[{"first_name":"Verena","id":"32B7C918-F248-11E8-B48F-1D18A9856A87","last_name":"Hübschmann","full_name":"Hübschmann, Verena"},{"orcid":"0000-0003-4309-2251","last_name":"Korkut","full_name":"Korkut, Medina","first_name":"Medina","id":"4B51CE74-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-8635-0877","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","first_name":"Sandra","full_name":"Siegert, Sandra","last_name":"Siegert"}],"ec_funded":1,"acknowledgement":"This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant No. 715571 to S.S.) and from the Gesellschaft für Forschungsförderung Niederösterreich (grant No. Sc19-017 to V.H.). We thank Rouven Schulz and Alessandro Venturino for their insights into functional assays and data analysis, Verena Seiboth for insights into necessary institutional permission, and ISTA imaging & optics facility (IOF) especially Bernhard Hochreiter for their support.","publication_status":"published","status":"public","project":[{"call_identifier":"H2020","name":"Microglia action towards neuronal circuit formation and function in health and disease","_id":"25D4A630-B435-11E9-9278-68D0E5697425","grant_number":"715571"},{"grant_number":"SC19-017","_id":"9B99D380-BA93-11EA-9121-9846C619BF3A","name":"How human microglia shape developing neurons during health and inflammation"}],"publication_identifier":{"issn":["2666-1667"]},"oa_version":"Published Version","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","month":"12","ddc":["570"],"file_date_updated":"2023-01-23T09:50:51Z","citation":{"ieee":"V. Hübschmann, M. Korkut, and S. Siegert, “Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay,” STAR Protocols, vol. 3, no. 4. Elsevier, 2022.","apa":"Hübschmann, V., Korkut, M., & Siegert, S. (2022). Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay. STAR Protocols. Elsevier. https://doi.org/10.1016/j.xpro.2022.101866","short":"V. Hübschmann, M. Korkut, S. Siegert, STAR Protocols 3 (2022).","ama":"Hübschmann V, Korkut M, Siegert S. Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay. STAR Protocols. 2022;3(4). doi:10.1016/j.xpro.2022.101866","ista":"Hübschmann V, Korkut M, Siegert S. 2022. Assessing human iPSC-derived microglia identity and function by immunostaining, phagocytosis, calcium activity, and inflammation assay. STAR Protocols. 3(4), 101866.","chicago":"Hübschmann, Verena, Medina Korkut, and Sandra Siegert. “Assessing Human IPSC-Derived Microglia Identity and Function by Immunostaining, Phagocytosis, Calcium Activity, and Inflammation Assay.” STAR Protocols. Elsevier, 2022. https://doi.org/10.1016/j.xpro.2022.101866.","mla":"Hübschmann, Verena, et al. “Assessing Human IPSC-Derived Microglia Identity and Function by Immunostaining, Phagocytosis, Calcium Activity, and Inflammation Assay.” STAR Protocols, vol. 3, no. 4, 101866, Elsevier, 2022, doi:10.1016/j.xpro.2022.101866."},"day":"16","volume":3,"article_processing_charge":"No","has_accepted_license":"1","file":[{"file_id":"12340","date_created":"2023-01-23T09:50:51Z","file_name":"2022_STARProtocols_Huebschmann.pdf","creator":"dernst","file_size":6251945,"relation":"main_file","access_level":"open_access","checksum":"3c71b8a60633d42c2f77c49025d5559b","content_type":"application/pdf","success":1,"date_updated":"2023-01-23T09:50:51Z"}],"tmp":{"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)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"}},{"oa_version":"Published Version","pmid":1,"month":"12","ddc":["570"],"file_date_updated":"2023-01-23T10:18:48Z","citation":{"apa":"Petzold, T., Zhang, Z., Ballesteros, I., Saleh, I., Polzin, A., Thienel, M., … Massberg, S. (2022). Neutrophil “plucking” on megakaryocytes drives platelet production and boosts cardiovascular disease. Immunity. Elsevier. https://doi.org/10.1016/j.immuni.2022.10.001","ieee":"T. Petzold et al., “Neutrophil ‘plucking’ on megakaryocytes drives platelet production and boosts cardiovascular disease,” Immunity, vol. 55, no. 12. Elsevier, p. 2285–2299.e7, 2022.","short":"T. Petzold, Z. Zhang, I. Ballesteros, I. Saleh, A. Polzin, M. Thienel, L. Liu, Q. Ul Ain, V. Ehreiser, C. Weber, B. Kilani, P. Mertsch, J. Götschke, S. Cremer, W. Fu, M. Lorenz, H. Ishikawa-Ankerhold, E. Raatz, S. El-Nemr, A. Görlach, E. Marhuenda, K. Stark, J. Pircher, D. Stegner, C. Gieger, M. Schmidt-Supprian, F.R. Gärtner, I. Almendros, M. Kelm, C. Schulz, A. Hidalgo, S. Massberg, Immunity 55 (2022) 2285–2299.e7.","ama":"Petzold T, Zhang Z, Ballesteros I, et al. Neutrophil “plucking” on megakaryocytes drives platelet production and boosts cardiovascular disease. Immunity. 2022;55(12):2285-2299.e7. doi:10.1016/j.immuni.2022.10.001","ista":"Petzold T, Zhang Z, Ballesteros I, Saleh I, Polzin A, Thienel M, Liu L, Ul Ain Q, Ehreiser V, Weber C, Kilani B, Mertsch P, Götschke J, Cremer S, Fu W, Lorenz M, Ishikawa-Ankerhold H, Raatz E, El-Nemr S, Görlach A, Marhuenda E, Stark K, Pircher J, Stegner D, Gieger C, Schmidt-Supprian M, Gärtner FR, Almendros I, Kelm M, Schulz C, Hidalgo A, Massberg S. 2022. Neutrophil “plucking” on megakaryocytes drives platelet production and boosts cardiovascular disease. Immunity. 55(12), 2285–2299.e7.","chicago":"Petzold, Tobias, Zhe Zhang, Iván Ballesteros, Inas Saleh, Amin Polzin, Manuela Thienel, Lulu Liu, et al. “Neutrophil ‘Plucking’ on Megakaryocytes Drives Platelet Production and Boosts Cardiovascular Disease.” Immunity. Elsevier, 2022. https://doi.org/10.1016/j.immuni.2022.10.001.","mla":"Petzold, Tobias, et al. “Neutrophil ‘Plucking’ on Megakaryocytes Drives Platelet Production and Boosts Cardiovascular Disease.” Immunity, vol. 55, no. 12, Elsevier, 2022, p. 2285–2299.e7, doi:10.1016/j.immuni.2022.10.001."},"day":"13","article_processing_charge":"No","volume":55,"has_accepted_license":"1","file":[{"date_created":"2023-01-23T10:18:48Z","file_id":"12341","content_type":"application/pdf","checksum":"073267a9c0ad9f85a650053bc7b23777","access_level":"open_access","date_updated":"2023-01-23T10:18:48Z","success":1,"file_size":5299475,"creator":"dernst","relation":"main_file","file_name":"2022_Immunity_Petzold.pdf"}],"tmp":{"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)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode"},"doi":"10.1016/j.immuni.2022.10.001","abstract":[{"lang":"eng","text":"Intravascular neutrophils and platelets collaborate in maintaining host integrity, but their interaction can also trigger thrombotic complications. We report here that cooperation between neutrophil and platelet lineages extends to the earliest stages of platelet formation by megakaryocytes in the bone marrow. Using intravital microscopy, we show that neutrophils “plucked” intravascular megakaryocyte extensions, termed proplatelets, to control platelet production. Following CXCR4-CXCL12-dependent migration towards perisinusoidal megakaryocytes, plucking neutrophils actively pulled on proplatelets and triggered myosin light chain and extracellular-signal-regulated kinase activation through reactive oxygen species. By these mechanisms, neutrophils accelerate proplatelet growth and facilitate continuous release of platelets in steady state. Following myocardial infarction, plucking neutrophils drove excessive release of young, reticulated platelets and boosted the risk of recurrent ischemia. Ablation of neutrophil plucking normalized thrombopoiesis and reduced recurrent thrombosis after myocardial infarction and thrombus burden in venous thrombosis. We establish neutrophil plucking as a target to reduce thromboischemic events."}],"issue":"12","_id":"12119","title":"Neutrophil “plucking” on megakaryocytes drives platelet production and boosts cardiovascular disease","author":[{"full_name":"Petzold, Tobias","last_name":"Petzold","first_name":"Tobias"},{"last_name":"Zhang","full_name":"Zhang, Zhe","first_name":"Zhe"},{"last_name":"Ballesteros","full_name":"Ballesteros, Iván","first_name":"Iván"},{"last_name":"Saleh","full_name":"Saleh, Inas","first_name":"Inas"},{"last_name":"Polzin","full_name":"Polzin, Amin","first_name":"Amin"},{"last_name":"Thienel","full_name":"Thienel, Manuela","first_name":"Manuela"},{"full_name":"Liu, Lulu","last_name":"Liu","first_name":"Lulu"},{"last_name":"Ul Ain","full_name":"Ul Ain, Qurrat","first_name":"Qurrat"},{"full_name":"Ehreiser, Vincent","last_name":"Ehreiser","first_name":"Vincent"},{"last_name":"Weber","full_name":"Weber, Christian","first_name":"Christian"},{"first_name":"Badr","last_name":"Kilani","full_name":"Kilani, Badr"},{"first_name":"Pontus","last_name":"Mertsch","full_name":"Mertsch, Pontus"},{"last_name":"Götschke","full_name":"Götschke, Jeremias","first_name":"Jeremias"},{"full_name":"Cremer, Sophie","last_name":"Cremer","first_name":"Sophie"},{"first_name":"Wenwen","full_name":"Fu, Wenwen","last_name":"Fu"},{"last_name":"Lorenz","full_name":"Lorenz, Michael","first_name":"Michael"},{"first_name":"Hellen","full_name":"Ishikawa-Ankerhold, Hellen","last_name":"Ishikawa-Ankerhold"},{"full_name":"Raatz, Elisabeth","last_name":"Raatz","first_name":"Elisabeth"},{"last_name":"El-Nemr","full_name":"El-Nemr, Shaza","first_name":"Shaza"},{"full_name":"Görlach, Agnes","last_name":"Görlach","first_name":"Agnes"},{"first_name":"Esther","full_name":"Marhuenda, Esther","last_name":"Marhuenda"},{"last_name":"Stark","full_name":"Stark, Konstantin","first_name":"Konstantin"},{"first_name":"Joachim","last_name":"Pircher","full_name":"Pircher, Joachim"},{"full_name":"Stegner, David","last_name":"Stegner","first_name":"David"},{"last_name":"Gieger","full_name":"Gieger, Christian","first_name":"Christian"},{"full_name":"Schmidt-Supprian, Marc","last_name":"Schmidt-Supprian","first_name":"Marc"},{"last_name":"Gärtner","full_name":"Gärtner, Florian R","first_name":"Florian R","id":"397A88EE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6120-3723"},{"full_name":"Almendros, Isaac","last_name":"Almendros","first_name":"Isaac"},{"full_name":"Kelm, Malte","last_name":"Kelm","first_name":"Malte"},{"full_name":"Schulz, Christian","last_name":"Schulz","first_name":"Christian"},{"full_name":"Hidalgo, Andrés","last_name":"Hidalgo","first_name":"Andrés"},{"first_name":"Steffen","last_name":"Massberg","full_name":"Massberg, Steffen"}],"ec_funded":1,"status":"public","acknowledgement":"We thank Coung Kieu and Dominik van den Heuvel for excellent technical assistance. This work was supported by the German Research Foundation (PE2704/2-1, PE2704/3-1 to T.P., SFB 1123-project B06 to S.M., SFB1525 project A07 to D.S, TRR 332 project A7 to C.S., PO 2247/2-1 to A.P., SFB1116-project B11 to A.P. and B12 to M.K.), LMU Munich’s Institutional\r\nStrategy LMUexcellent within the framework of the German Excellence Initiative (No. 806 32 006 to T.P.), and by the German Centre for Cardiovascular Research (DZHK) to T.P. (Postdoc Start-up grant No. 100378833). This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No. 833440 to S.M.). F.G. received funding from the European Union’s\r\nHorizon 2020 research and innovation program under the Marie Sk1odowska-Curie grant agreement no. 747687. A.H. was funded by RTI2018-095497-B-I00 from Ministerio de Ciencia e Innovacio´ n (MICINN), HR17_00527 from Fundacion La Caixa, and Transatlantic Network of Excellence (TNE-18CVD04) from the Leducq Foundation. The CNIC is supported by the MICINN and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence (CEX2020-001041-S). A.P. was supported by the Forschungskommission of the Medical Faculty of the Heinrich-Heine-Universität Düsseldorf (No. 18-2019 to A.P.). C.G. was supported by the Helmholtz Alliance ‘Aging and Metabolic Programming, AMPro,’ by the German Federal\r\nMinistry of Education and Research to the German Center for Diabetes Research (DZD), and by the Bavarian State Ministry of Health and Care through the research project DigiMed Bayern.","publication_status":"published","project":[{"name":"Mechanical Adaptation of Lamellipodial Actin Networks in Migrating Cells","call_identifier":"H2020","grant_number":"747687","_id":"260AA4E2-B435-11E9-9278-68D0E5697425"}],"publication_identifier":{"issn":["1074-7613"]},"date_created":"2023-01-12T11:56:54Z","scopus_import":"1","date_published":"2022-12-13T00:00:00Z","external_id":{"isi":["000922019600003"],"pmid":["36272416"]},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"MiSi"}],"quality_controlled":"1","type":"journal_article","language":[{"iso":"eng"}],"isi":1,"publisher":"Elsevier","intvolume":" 55","keyword":["Infectious Diseases","Immunology","Immunology and Allergy"],"year":"2022","oa":1,"page":"2285-2299.e7","article_type":"original","date_updated":"2023-08-03T14:21:51Z","publication":"Immunity"},{"publisher":"Springer Nature","intvolume":" 7","type":"journal_article","language":[{"iso":"eng"}],"quality_controlled":"1","isi":1,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"FyKo"}],"date_created":"2023-01-12T12:02:54Z","scopus_import":"1","external_id":{"pmid":["36379998"],"isi":["000884278600004"]},"date_published":"2022-11-15T00:00:00Z","date_updated":"2023-08-04T08:52:40Z","publication":"npj Vaccines","article_number":"145","article_type":"original","oa":1,"keyword":["Pharmacology (medical)","Infectious Diseases","Pharmacology","Immunology","SARS-COV-2","COVID"],"year":"2022","file":[{"relation":"main_file","creator":"dernst","file_size":1856046,"file_name":"2022_njpVaccines_Byazrova.pdf","date_updated":"2023-01-23T11:22:09Z","success":1,"checksum":"ddaac096381565b2b4b7dcc34cdbc4ee","content_type":"application/pdf","access_level":"open_access","date_created":"2023-01-23T11:22:09Z","file_id":"12347"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"volume":7,"article_processing_charge":"No","has_accepted_license":"1","pmid":1,"month":"11","ddc":["570"],"file_date_updated":"2023-01-23T11:22:09Z","citation":{"ama":"Byazrova MG, Astakhova EA, Minnegalieva A, et al. Anti-Ad26 humoral immunity does not compromise SARS-COV-2 neutralizing antibody responses following Gam-COVID-Vac booster vaccination. npj Vaccines. 2022;7. doi:10.1038/s41541-022-00566-x","short":"M.G. Byazrova, E.A. Astakhova, A. Minnegalieva, M.M. Sukhova, A.A. Mikhailov, A.G. Prilipov, A.A. Gorchakov, A.V. Filatov, Npj Vaccines 7 (2022).","ista":"Byazrova MG, Astakhova EA, Minnegalieva A, Sukhova MM, Mikhailov AA, Prilipov AG, Gorchakov AA, Filatov AV. 2022. Anti-Ad26 humoral immunity does not compromise SARS-COV-2 neutralizing antibody responses following Gam-COVID-Vac booster vaccination. npj Vaccines. 7, 145.","apa":"Byazrova, M. G., Astakhova, E. A., Minnegalieva, A., Sukhova, M. M., Mikhailov, A. A., Prilipov, A. G., … Filatov, A. V. (2022). Anti-Ad26 humoral immunity does not compromise SARS-COV-2 neutralizing antibody responses following Gam-COVID-Vac booster vaccination. Npj Vaccines. Springer Nature. https://doi.org/10.1038/s41541-022-00566-x","ieee":"M. G. Byazrova et al., “Anti-Ad26 humoral immunity does not compromise SARS-COV-2 neutralizing antibody responses following Gam-COVID-Vac booster vaccination,” npj Vaccines, vol. 7. Springer Nature, 2022.","mla":"Byazrova, Maria G., et al. “Anti-Ad26 Humoral Immunity Does Not Compromise SARS-COV-2 Neutralizing Antibody Responses Following Gam-COVID-Vac Booster Vaccination.” Npj Vaccines, vol. 7, 145, Springer Nature, 2022, doi:10.1038/s41541-022-00566-x.","chicago":"Byazrova, Maria G., Ekaterina A. Astakhova, Aygul Minnegalieva, Maria M. Sukhova, Artem A. Mikhailov, Alexey G. Prilipov, Andrey A. Gorchakov, and Alexander V. Filatov. “Anti-Ad26 Humoral Immunity Does Not Compromise SARS-COV-2 Neutralizing Antibody Responses Following Gam-COVID-Vac Booster Vaccination.” Npj Vaccines. Springer Nature, 2022. https://doi.org/10.1038/s41541-022-00566-x."},"day":"15","oa_version":"Published Version","publication_identifier":{"issn":["2059-0105"]},"publication_status":"published","status":"public","acknowledgement":"We thank Sergey Kulemzin, Grigory Efimov, Yuri Lebedin, Alexander Taranin and Rudolf Valenta for providing reagents. Figures were created with the help of BioRender.com. This work was supported by the Russian Science Foundation (Project 21-15-00286). Byazrova M.G. was supported by the RUDN University Strategic Academic Leadership Program.","_id":"12131","title":"Anti-Ad26 humoral immunity does not compromise SARS-COV-2 neutralizing antibody responses following Gam-COVID-Vac booster vaccination","author":[{"first_name":"Maria G.","full_name":"Byazrova, Maria G.","last_name":"Byazrova"},{"first_name":"Ekaterina A.","last_name":"Astakhova","full_name":"Astakhova, Ekaterina A."},{"last_name":"Minnegalieva","full_name":"Minnegalieva, Aygul","first_name":"Aygul","id":"87DF77F0-1D9A-11EA-B6AE-CE443DDC885E"},{"last_name":"Sukhova","full_name":"Sukhova, Maria M.","first_name":"Maria M."},{"first_name":"Artem A.","full_name":"Mikhailov, Artem A.","last_name":"Mikhailov"},{"first_name":"Alexey G.","last_name":"Prilipov","full_name":"Prilipov, Alexey G."},{"last_name":"Gorchakov","full_name":"Gorchakov, Andrey A.","first_name":"Andrey A."},{"first_name":"Alexander V.","last_name":"Filatov","full_name":"Filatov, Alexander V."}],"doi":"10.1038/s41541-022-00566-x","abstract":[{"lang":"eng","text":"Replication-incompetent adenoviral vectors have been extensively used as a platform for vaccine design, with at least four anti-COVID-19 vaccines authorized to date. These vaccines elicit neutralizing antibody responses directed against SARS-CoV-2 Spike protein and confer significant level of protection against SARS-CoV-2 infection. Immunization with adenovirus-vectored vaccines is known to be accompanied by the production of anti-vector antibodies, which may translate into reduced efficacy of booster or repeated rounds of revaccination. Here, we used blood samples from patients who received an adenovirus-based Gam-COVID-Vac vaccine to address the question of whether anti-vector antibodies may influence the magnitude of SARS-CoV-2-specific humoral response after booster vaccination. We observed that rAd26-based prime vaccination with Gam-COVID-Vac induced the development of Ad26-neutralizing antibodies, which persisted in circulation for at least 9 months. Our analysis further indicates that high pre-boost Ad26 neutralizing antibody titers do not appear to affect the humoral immunogenicity of the Gam-COVID-Vac boost. The titers of anti-SARS-CoV-2 RBD IgGs and antibodies, which neutralized both the wild type and the circulating variants of concern of SARS-CoV-2 such as Delta and Omicron, were independent of the pre-boost levels of Ad26-neutralizing antibodies. Thus, our results support the development of repeated immunization schedule with adenovirus-based COVID-19 vaccines."}]},{"department":[{"_id":"NiBa"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","external_id":{"isi":["000890735600001"]},"date_published":"2022-09-26T00:00:00Z","date_created":"2023-01-12T12:09:00Z","scopus_import":"1","publisher":"eLife Sciences Publications","intvolume":" 11","isi":1,"quality_controlled":"1","language":[{"iso":"eng"}],"type":"journal_article","oa":1,"year":"2022","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"publication":"eLife","date_updated":"2023-08-04T09:04:58Z","article_number":"66697","article_type":"original","citation":{"chicago":"Hayward, Laura, and Guy Sella. “Polygenic Adaptation after a Sudden Change in Environment.” ELife. eLife Sciences Publications, 2022. https://doi.org/10.7554/elife.66697.","mla":"Hayward, Laura, and Guy Sella. “Polygenic Adaptation after a Sudden Change in Environment.” ELife, vol. 11, 66697, eLife Sciences Publications, 2022, doi:10.7554/elife.66697.","ista":"Hayward L, Sella G. 2022. Polygenic adaptation after a sudden change in environment. eLife. 11, 66697.","ama":"Hayward L, Sella G. Polygenic adaptation after a sudden change in environment. eLife. 2022;11. doi:10.7554/elife.66697","short":"L. Hayward, G. Sella, ELife 11 (2022).","apa":"Hayward, L., & Sella, G. (2022). Polygenic adaptation after a sudden change in environment. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.66697","ieee":"L. Hayward and G. Sella, “Polygenic adaptation after a sudden change in environment,” eLife, vol. 11. eLife Sciences Publications, 2022."},"day":"26","month":"09","ddc":["570"],"file_date_updated":"2023-01-24T12:21:32Z","oa_version":"Published Version","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"file":[{"file_id":"12363","date_created":"2023-01-24T12:21:32Z","access_level":"open_access","content_type":"application/pdf","checksum":"28de155b231ac1c8d4501c98b2fb359a","success":1,"date_updated":"2023-01-24T12:21:32Z","file_name":"2022_eLife_Hayward.pdf","creator":"dernst","file_size":18935612,"relation":"main_file"}],"has_accepted_license":"1","volume":11,"article_processing_charge":"No","title":"Polygenic adaptation after a sudden change in environment","author":[{"id":"fc885ee5-24bf-11eb-ad7b-bcc5104c0c1b","first_name":"Laura","full_name":"Hayward, Laura","last_name":"Hayward"},{"first_name":"Guy","full_name":"Sella, Guy","last_name":"Sella"}],"_id":"12157","abstract":[{"lang":"eng","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."}],"doi":"10.7554/elife.66697","publication_identifier":{"eissn":["2050-084X"]},"publication_status":"published","status":"public","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"},{"publication_status":"published","status":"public","acknowledgement":"The authors declare that this study received funding from Immunofusion. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication.","publication_identifier":{"issn":["1664-3224"]},"doi":"10.3389/fimmu.2022.965446","abstract":[{"lang":"eng","text":"The COVID−19 pandemic not only resulted in a global crisis, but also accelerated vaccine development and antibody discovery. Herein we report a synthetic humanized VHH library development pipeline for nanomolar-range affinity VHH binders to SARS-CoV-2 variants of concern (VoC) receptor binding domains (RBD) isolation. Trinucleotide-based randomization of CDRs by Kunkel mutagenesis with the subsequent rolling-cycle amplification resulted in more than 1011 diverse phage display library in a manageable for a single person number of electroporation reactions. We identified a number of nanomolar-range affinity VHH binders to SARS-CoV-2 variants of concern (VoC) receptor binding domains (RBD) by screening a novel synthetic humanized antibody library. In order to explore the most robust and fast method for affinity improvement, we performed affinity maturation by CDR1 and CDR2 shuffling and avidity engineering by multivalent trimeric VHH fusion protein construction. As a result, H7-Fc and G12x3-Fc binders were developed with the affinities in nM and pM range respectively. Importantly, these affinities are weakly influenced by most of SARS-CoV-2 VoC mutations and they retain moderate binding to BA.4\\5. The plaque reduction neutralization test (PRNT) resulted in IC50 = 100 ng\\ml and 9.6 ng\\ml for H7-Fc and G12x3-Fc antibodies, respectively, for the emerging Omicron BA.1 variant. Therefore, these VHH could expand the present landscape of SARS-CoV-2 neutralization binders with the therapeutic potential for present and future SARS-CoV-2 variants."}],"_id":"12252","title":"Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library","author":[{"last_name":"Dormeshkin","full_name":"Dormeshkin, Dmitri","first_name":"Dmitri"},{"first_name":"Michail","full_name":"Shapira, Michail","last_name":"Shapira"},{"last_name":"Dubovik","full_name":"Dubovik, Simon","first_name":"Simon"},{"orcid":"0000-0003-2091-526X","full_name":"Kavaleuski, Anton","last_name":"Kavaleuski","id":"4968f7ad-eb97-11eb-a6c2-8ed382e8912c","first_name":"Anton"},{"first_name":"Mikalai","last_name":"Katsin","full_name":"Katsin, Mikalai"},{"full_name":"Migas, Alexandr","last_name":"Migas","first_name":"Alexandr"},{"full_name":"Meleshko, Alexander","last_name":"Meleshko","first_name":"Alexander"},{"last_name":"Semyonov","full_name":"Semyonov, Sergei","first_name":"Sergei"}],"article_processing_charge":"No","volume":13,"has_accepted_license":"1","file":[{"file_id":"12443","date_created":"2023-01-30T09:22:26Z","file_name":"2022_FrontiersImmunology_Dormeshkin.pdf","relation":"main_file","file_size":5695892,"creator":"dernst","success":1,"date_updated":"2023-01-30T09:22:26Z","access_level":"open_access","checksum":"f8f5d8110710033d0532e7e08bf9dad4","content_type":"application/pdf"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"oa_version":"Published Version","ddc":["570"],"file_date_updated":"2023-01-30T09:22:26Z","month":"09","citation":{"chicago":"Dormeshkin, Dmitri, Michail Shapira, Simon Dubovik, Anton Kavaleuski, Mikalai Katsin, Alexandr Migas, Alexander Meleshko, and Sergei Semyonov. “Isolation of an Escape-Resistant SARS-CoV-2 Neutralizing Nanobody from a Novel Synthetic Nanobody Library.” Frontiers in Immunology. Frontiers Media, 2022. https://doi.org/10.3389/fimmu.2022.965446.","mla":"Dormeshkin, Dmitri, et al. “Isolation of an Escape-Resistant SARS-CoV-2 Neutralizing Nanobody from a Novel Synthetic Nanobody Library.” Frontiers in Immunology, vol. 13, 965446, Frontiers Media, 2022, doi:10.3389/fimmu.2022.965446.","ieee":"D. Dormeshkin et al., “Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library,” Frontiers in Immunology, vol. 13. Frontiers Media, 2022.","apa":"Dormeshkin, D., Shapira, M., Dubovik, S., Kavaleuski, A., Katsin, M., Migas, A., … Semyonov, S. (2022). Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library. Frontiers in Immunology. Frontiers Media. https://doi.org/10.3389/fimmu.2022.965446","ama":"Dormeshkin D, Shapira M, Dubovik S, et al. Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library. Frontiers in Immunology. 2022;13. doi:10.3389/fimmu.2022.965446","ista":"Dormeshkin D, Shapira M, Dubovik S, Kavaleuski A, Katsin M, Migas A, Meleshko A, Semyonov S. 2022. Isolation of an escape-resistant SARS-CoV-2 neutralizing nanobody from a novel synthetic nanobody library. Frontiers in Immunology. 13, 965446.","short":"D. Dormeshkin, M. Shapira, S. Dubovik, A. Kavaleuski, M. Katsin, A. Migas, A. Meleshko, S. Semyonov, Frontiers in Immunology 13 (2022)."},"day":"16","article_number":"965446","article_type":"original","date_updated":"2023-08-04T09:49:24Z","publication":"Frontiers in Immunology","keyword":["Immunology","Immunology and Allergy","COVID-19","SARS-CoV-2","synthetic library","RBD","neutralization nanobody","VHH"],"year":"2022","oa":1,"language":[{"iso":"eng"}],"type":"journal_article","quality_controlled":"1","isi":1,"publisher":"Frontiers Media","intvolume":" 13","date_created":"2023-01-16T09:56:57Z","scopus_import":"1","date_published":"2022-09-16T00:00:00Z","external_id":{"isi":["000862479100001"]},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"LeSa"}]},{"volume":18,"article_processing_charge":"No","has_accepted_license":"1","file":[{"file_name":"2022_MolecularSystemsBio_Angermayr.pdf","creator":"dernst","file_size":1098812,"relation":"main_file","success":1,"date_updated":"2023-01-30T09:49:55Z","access_level":"open_access","checksum":"8b1d8f5ea20c8408acf466435fb6ae01","content_type":"application/pdf","file_id":"12446","date_created":"2023-01-30T09:49:55Z"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"oa_version":"Published Version","file_date_updated":"2023-01-30T09:49:55Z","month":"09","ddc":["570"],"day":"01","citation":{"mla":"Angermayr, Andreas, et al. “Growth‐mediated Negative Feedback Shapes Quantitative Antibiotic Response.” Molecular Systems Biology, vol. 18, no. 9, e10490, Embo Press, 2022, doi:10.15252/msb.202110490.","chicago":"Angermayr, Andreas, Tin Yau Pang, Guillaume Chevereau, Karin Mitosch, Martin J Lercher, and Mark Tobias Bollenbach. “Growth‐mediated Negative Feedback Shapes Quantitative Antibiotic Response.” Molecular Systems Biology. Embo Press, 2022. https://doi.org/10.15252/msb.202110490.","apa":"Angermayr, A., Pang, T. Y., Chevereau, G., Mitosch, K., Lercher, M. J., & Bollenbach, M. T. (2022). Growth‐mediated negative feedback shapes quantitative antibiotic response. Molecular Systems Biology. Embo Press. https://doi.org/10.15252/msb.202110490","ieee":"A. Angermayr, T. Y. Pang, G. Chevereau, K. Mitosch, M. J. Lercher, and M. T. Bollenbach, “Growth‐mediated negative feedback shapes quantitative antibiotic response,” Molecular Systems Biology, vol. 18, no. 9. Embo Press, 2022.","short":"A. Angermayr, T.Y. Pang, G. Chevereau, K. Mitosch, M.J. Lercher, M.T. Bollenbach, Molecular Systems Biology 18 (2022).","ama":"Angermayr A, Pang TY, Chevereau G, Mitosch K, Lercher MJ, Bollenbach MT. Growth‐mediated negative feedback shapes quantitative antibiotic response. Molecular Systems Biology. 2022;18(9). doi:10.15252/msb.202110490","ista":"Angermayr A, Pang TY, Chevereau G, Mitosch K, Lercher MJ, Bollenbach MT. 2022. Growth‐mediated negative feedback shapes quantitative antibiotic response. Molecular Systems Biology. 18(9), e10490."},"status":"public","publication_status":"published","acknowledgement":"This work was in part supported by Human Frontier Science Program GrantRGP0042/2013, Marie Curie Career Integration Grant303507, AustrianScience Fund (FWF) Grant P27201-B22, and German Research Foundation(DFG) Collaborative Research Center (SFB)1310to TB. SAA was supportedby the European Union’s Horizon2020Research and Innovation Programunder the Marie Skłodowska-Curie Grant agreement No707352. We wouldlike to thank the Bollenbach group for regular fruitful discussions. We areparticularly thankful for the technical assistance of Booshini Fernando andfor discussions of the theoretical aspects with Gerrit Ansmann. We areindebted to Bor Kavˇciˇc for invaluable advice, help with setting up theluciferase-based growth monitoring system, and for sharing plasmids. Weacknowledge the IST Austria Miba Machine Shop for their support inbuilding a housing for the stacker of the plate reader, which enabled thehigh-throughput luciferase-based experiments. We are grateful to RosalindAllen, Bor Kavˇciˇc and Dor Russ for feedback on the manuscript. Open Accessfunding enabled and organized by Projekt DEAL.","publication_identifier":{"eissn":["1744-4292"]},"doi":"10.15252/msb.202110490","issue":"9","abstract":[{"lang":"eng","text":"Dose–response relationships are a general concept for quantitatively describing biological systems across multiple scales, from the molecular to the whole-cell level. A clinically relevant example is the bacterial growth response to antibiotics, which is routinely characterized by dose–response curves. The shape of the dose–response curve varies drastically between antibiotics and plays a key role in treatment, drug interactions, and resistance evolution. However, the mechanisms shaping the dose–response curve remain largely unclear. Here, we show in Escherichia coli that the distinctively shallow dose–response curve of the antibiotic trimethoprim is caused by a negative growth-mediated feedback loop: Trimethoprim slows growth, which in turn weakens the effect of this antibiotic. At the molecular level, this feedback is caused by the upregulation of the drug target dihydrofolate reductase (FolA/DHFR). We show that this upregulation is not a specific response to trimethoprim but follows a universal trend line that depends primarily on the growth rate, irrespective of its cause. Rewiring the feedback loop alters the dose–response curve in a predictable manner, which we corroborate using a mathematical model of cellular resource allocation and growth. Our results indicate that growth-mediated feedback loops may shape drug responses more generally and could be exploited to design evolutionary traps that enable selection against drug resistance."}],"_id":"12261","author":[{"full_name":"Angermayr, Andreas","last_name":"Angermayr","id":"4677C796-F248-11E8-B48F-1D18A9856A87","first_name":"Andreas","orcid":"0000-0001-8619-2223"},{"first_name":"Tin Yau","last_name":"Pang","full_name":"Pang, Tin Yau"},{"full_name":"Chevereau, Guillaume","last_name":"Chevereau","first_name":"Guillaume"},{"full_name":"Mitosch, Karin","last_name":"Mitosch","id":"39B66846-F248-11E8-B48F-1D18A9856A87","first_name":"Karin"},{"full_name":"Lercher, Martin J","last_name":"Lercher","first_name":"Martin J"},{"orcid":"0000-0003-4398-476X","full_name":"Bollenbach, Mark Tobias","last_name":"Bollenbach","id":"3E6DB97A-F248-11E8-B48F-1D18A9856A87","first_name":"Mark Tobias"}],"title":"Growth‐mediated negative feedback shapes quantitative antibiotic response","type":"journal_article","language":[{"iso":"eng"}],"quality_controlled":"1","isi":1,"intvolume":" 18","publisher":"Embo Press","scopus_import":"1","acknowledged_ssus":[{"_id":"M-Shop"}],"date_created":"2023-01-16T09:58:34Z","date_published":"2022-09-01T00:00:00Z","external_id":{"isi":["000856482800001"]},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"ToBo"}],"article_type":"original","article_number":"e10490","date_updated":"2023-08-04T09:51:49Z","publication":"Molecular Systems Biology","keyword":["Applied Mathematics","Computational Theory and Mathematics","General Agricultural and Biological Sciences","General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","Information Systems"],"year":"2022","oa":1},{"volume":11,"article_processing_charge":"No","has_accepted_license":"1","file":[{"date_created":"2023-01-30T11:50:53Z","file_id":"12463","relation":"main_file","creator":"dernst","file_size":8506811,"file_name":"2022_eLife_Sumser.pdf","content_type":"application/pdf","checksum":"5a2a65e3e7225090c3d8199f3bbd7b7b","access_level":"open_access","date_updated":"2023-01-30T11:50:53Z","success":1}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"oa_version":"Published Version","ddc":["570"],"file_date_updated":"2023-01-30T11:50:53Z","month":"09","pmid":1,"citation":{"apa":"Sumser, A. L., Jösch, M. A., Jonas, P. M., & Ben Simon, Y. (2022). Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.79848","ieee":"A. L. Sumser, M. A. Jösch, P. M. Jonas, and Y. Ben Simon, “Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling,” eLife, vol. 11. eLife Sciences Publications, 2022.","ista":"Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. 2022. Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. eLife. 11, 79848.","ama":"Sumser AL, Jösch MA, Jonas PM, Ben Simon Y. Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling. eLife. 2022;11. doi:10.7554/elife.79848","short":"A.L. Sumser, M.A. Jösch, P.M. Jonas, Y. Ben Simon, ELife 11 (2022).","mla":"Sumser, Anton L., et al. “Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.” ELife, vol. 11, 79848, eLife Sciences Publications, 2022, doi:10.7554/elife.79848.","chicago":"Sumser, Anton L, Maximilian A Jösch, Peter M Jonas, and Yoav Ben Simon. “Fast, High-Throughput Production of Improved Rabies Viral Vectors for Specific, Efficient and Versatile Transsynaptic Retrograde Labeling.” ELife. eLife Sciences Publications, 2022. https://doi.org/10.7554/elife.79848."},"day":"15","ec_funded":1,"publication_status":"published","acknowledgement":"We thank F Marr for technical assistance, A Murray for RVdG-CVS-N2c viruses and Neuro2A packaging cell-lines and J Watson for reading the manuscript. This research was supported by the Scientific Service Units (SSU) of IST-Austria through resources provided by the Imaging and Optics Facility (IOF) and the Preclinical Facility (PCF). This project was funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC advanced grant No 692692, PJ, ERC starting grant No 756502, MJ), the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award, PJ), the Human Frontier Science Program (LT000256/2018-L, AS) and EMBO (ALTF 1098-2017, AS).","status":"public","project":[{"call_identifier":"H2020","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"name":"Circuits of Visual Attention","call_identifier":"H2020","grant_number":"756502","_id":"2634E9D2-B435-11E9-9278-68D0E5697425"},{"name":"The Wittgenstein Prize","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312"},{"name":"Neuronal networks of salience and spatial detection in the murine superior colliculus","grant_number":"LT000256","_id":"266D407A-B435-11E9-9278-68D0E5697425"},{"name":"Connecting sensory with motor processing in the superior colliculus","grant_number":"ALTF 1098-2017","_id":"264FEA02-B435-11E9-9278-68D0E5697425"}],"publication_identifier":{"eissn":["2050-084X"]},"doi":"10.7554/elife.79848","abstract":[{"lang":"eng","text":"To understand the function of neuronal circuits, it is crucial to disentangle the connectivity patterns within the network. However, most tools currently used to explore connectivity have low throughput, low selectivity, or limited accessibility. Here, we report the development of an improved packaging system for the production of the highly neurotropic RVdGenvA-CVS-N2c rabies viral vectors, yielding titers orders of magnitude higher with no background contamination, at a fraction of the production time, while preserving the efficiency of transsynaptic labeling. Along with the production pipeline, we developed suites of ‘starter’ AAV and bicistronic RVdG-CVS-N2c vectors, enabling retrograde labeling from a wide range of neuronal populations, tailored for diverse experimental requirements. We demonstrate the power and flexibility of the new system by uncovering hidden local and distal inhibitory connections in the mouse hippocampal formation and by imaging the functional properties of a cortical microcircuit across weeks. Our novel production pipeline provides a convenient approach to generate new rabies vectors, while our toolkit flexibly and efficiently expands the current capacity to label, manipulate and image the neuronal activity of interconnected neuronal circuits in vitro and in vivo."}],"_id":"12288","title":"Fast, high-throughput production of improved rabies viral vectors for specific, efficient and versatile transsynaptic retrograde labeling","author":[{"last_name":"Sumser","full_name":"Sumser, Anton L","first_name":"Anton L","id":"3320A096-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-4792-1881"},{"full_name":"Jösch, Maximilian A","last_name":"Jösch","id":"2BD278E6-F248-11E8-B48F-1D18A9856A87","first_name":"Maximilian A","orcid":"0000-0002-3937-1330"},{"orcid":"0000-0001-5001-4804","last_name":"Jonas","full_name":"Jonas, Peter M","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"},{"id":"43DF3136-F248-11E8-B48F-1D18A9856A87","first_name":"Yoav","full_name":"Ben Simon, Yoav","last_name":"Ben Simon"}],"type":"journal_article","quality_controlled":"1","language":[{"iso":"eng"}],"isi":1,"publisher":"eLife Sciences Publications","intvolume":" 11","date_created":"2023-01-16T10:04:15Z","scopus_import":"1","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"external_id":{"isi":["000892204300001"],"pmid":["36040301"]},"date_published":"2022-09-15T00:00:00Z","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"MaJö"},{"_id":"PeJo"}],"article_number":"79848","article_type":"original","date_updated":"2023-08-04T10:29:48Z","publication":"eLife","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"year":"2022","oa":1},{"publisher":"Wiley","intvolume":" 76","isi":1,"quality_controlled":"1","type":"journal_article","language":[{"iso":"eng"}],"department":[{"_id":"Bio"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","date_published":"2021-05-01T00:00:00Z","external_id":{"isi":["000577708800001"],"pmid":["32990982"]},"date_created":"2022-03-08T11:19:05Z","scopus_import":"1","publication":"Allergy","date_updated":"2023-09-05T15:58:53Z","page":"1553-1556","article_type":"letter_note","oa":1,"year":"2021","keyword":["Immunology","Immunology and Allergy"],"file":[{"date_updated":"2022-03-08T11:23:16Z","success":1,"content_type":"application/pdf","checksum":"9526f9554112fc027c9f7fa540c488cd","access_level":"open_access","file_size":626081,"relation":"main_file","creator":"dernst","file_name":"2021_Allergy_Pranger.pdf","date_created":"2022-03-08T11:23:16Z","file_id":"10837"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"has_accepted_license":"1","article_processing_charge":"No","volume":76,"citation":{"chicago":"Pranger, Christina L., Judit Singer, Verena K. Köhler, Isabella Pali‐Schöll, Alessandro Fiocchi, Sophia N. Karagiannis, Olatz Zenarruzabeitia, Francisco Borrego, and Erika Jensen‐Jarolim. “PIPE‐cloned Human IgE and IgG4 Antibodies: New Tools for Investigating Cow’s Milk Allergy and Tolerance.” Allergy. Wiley, 2021. https://doi.org/10.1111/all.14604.","mla":"Pranger, Christina L., et al. “PIPE‐cloned Human IgE and IgG4 Antibodies: New Tools for Investigating Cow’s Milk Allergy and Tolerance.” Allergy, vol. 76, no. 5, Wiley, 2021, pp. 1553–56, doi:10.1111/all.14604.","apa":"Pranger, C. L., Singer, J., Köhler, V. K., Pali‐Schöll, I., Fiocchi, A., Karagiannis, S. N., … Jensen‐Jarolim, E. (2021). PIPE‐cloned human IgE and IgG4 antibodies: New tools for investigating cow’s milk allergy and tolerance. Allergy. Wiley. https://doi.org/10.1111/all.14604","ieee":"C. L. Pranger et al., “PIPE‐cloned human IgE and IgG4 antibodies: New tools for investigating cow’s milk allergy and tolerance,” Allergy, vol. 76, no. 5. Wiley, pp. 1553–1556, 2021.","short":"C.L. Pranger, J. Singer, V.K. Köhler, I. Pali‐Schöll, A. Fiocchi, S.N. Karagiannis, O. Zenarruzabeitia, F. Borrego, E. Jensen‐Jarolim, Allergy 76 (2021) 1553–1556.","ista":"Pranger CL, Singer J, Köhler VK, Pali‐Schöll I, Fiocchi A, Karagiannis SN, Zenarruzabeitia O, Borrego F, Jensen‐Jarolim E. 2021. PIPE‐cloned human IgE and IgG4 antibodies: New tools for investigating cow’s milk allergy and tolerance. Allergy. 76(5), 1553–1556.","ama":"Pranger CL, Singer J, Köhler VK, et al. PIPE‐cloned human IgE and IgG4 antibodies: New tools for investigating cow’s milk allergy and tolerance. Allergy. 2021;76(5):1553-1556. doi:10.1111/all.14604"},"day":"01","month":"05","pmid":1,"file_date_updated":"2022-03-08T11:23:16Z","ddc":["570"],"oa_version":"Published Version","publication_identifier":{"issn":["0105-4538"],"eissn":["1398-9995"]},"publication_status":"published","status":"public","acknowledgement":"This work was supported by the Austrian Science Fund (FWF) grants MCCA W1248-B30 and SFB F4606-B28 to EJJ. CP received a short-term research fellowship of the European Federation of Immunological Societies (EFIS-IL) for a research visit at Biocruces Bizkaia Health Research Institute, Barakaldo, Spain. VKK received an EFIS-IL short-term research fellowship for a research visit at King’s College London. The research was funded by the National Institute for Health Research (NIHR) Biomedical Research Centre (BRC) based at Guy's and St Thomas' NHS Foundation Trust and King's College London (IS-BRC-1215-20006) (SNK). The authors acknowledge support by the Medical Research Council (MR/L023091/1) (SNK); Breast Cancer Now (147; KCL-BCN-Q3)(SNK); Cancer Research UK (C30122/A11527; C30122/A15774) (SNK); Cancer Research UK King's Health Partners Centre at King's College London (C604/A25135) (SNK); CRUK/NIHR in England/DoH for Scotland, Wales and Northern Ireland Experimental Cancer Medicine Centre (C10355/A15587) (SNK). The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health. Additionally, this work was funded by Instituto de Salud Carlos III through the project \"PI16/01223\" (Co-funded by European Regional Development Fund; “A way to make Europe”) to FB and by the Department of Health, Basque Government through the project “2019111031” to OZ. OZ is recipient of a Sara Borrell 2017 post-doctoral contract “CD17/00128” funded by Instituto de Salud Carlos III (Co-funded by European Social Fund; “Investing in your future”).","title":"PIPE‐cloned human IgE and IgG4 antibodies: New tools for investigating cow's milk allergy and tolerance","author":[{"full_name":"Pranger, Christina L.","last_name":"Pranger","first_name":"Christina L."},{"orcid":"0000-0002-8777-3502","id":"36432834-F248-11E8-B48F-1D18A9856A87","first_name":"Judit","full_name":"Fazekas-Singer, Judit","last_name":"Fazekas-Singer"},{"first_name":"Verena K.","last_name":"Köhler","full_name":"Köhler, Verena K."},{"first_name":"Isabella","last_name":"Pali‐Schöll","full_name":"Pali‐Schöll, Isabella"},{"first_name":"Alessandro","full_name":"Fiocchi, Alessandro","last_name":"Fiocchi"},{"first_name":"Sophia N.","last_name":"Karagiannis","full_name":"Karagiannis, Sophia N."},{"first_name":"Olatz","last_name":"Zenarruzabeitia","full_name":"Zenarruzabeitia, Olatz"},{"first_name":"Francisco","full_name":"Borrego, Francisco","last_name":"Borrego"},{"first_name":"Erika","full_name":"Jensen‐Jarolim, Erika","last_name":"Jensen‐Jarolim"}],"_id":"10836","issue":"5","doi":"10.1111/all.14604"},{"article_processing_charge":"No","volume":524,"day":"24","citation":{"mla":"Khudiakova, Kseniia, et al. “Two Linked Loci under Mutation-Selection Balance and Muller’s Ratchet.” Journal of Theoretical Biology, vol. 524, 110729, Elsevier , 2021, doi:10.1016/j.jtbi.2021.110729.","chicago":"Khudiakova, Kseniia, Tatiana Yu. Neretina, and Alexey S. Kondrashov. “Two Linked Loci under Mutation-Selection Balance and Muller’s Ratchet.” Journal of Theoretical Biology. Elsevier , 2021. https://doi.org/10.1016/j.jtbi.2021.110729.","ieee":"K. Khudiakova, T. Y. Neretina, and A. S. Kondrashov, “Two linked loci under mutation-selection balance and Muller’s ratchet,” Journal of Theoretical Biology, vol. 524. Elsevier , 2021.","apa":"Khudiakova, K., Neretina, T. Y., & Kondrashov, A. S. (2021). Two linked loci under mutation-selection balance and Muller’s ratchet. Journal of Theoretical Biology. Elsevier . https://doi.org/10.1016/j.jtbi.2021.110729","ama":"Khudiakova K, Neretina TY, Kondrashov AS. Two linked loci under mutation-selection balance and Muller’s ratchet. Journal of Theoretical Biology. 2021;524. doi:10.1016/j.jtbi.2021.110729","ista":"Khudiakova K, Neretina TY, Kondrashov AS. 2021. Two linked loci under mutation-selection balance and Muller’s ratchet. Journal of Theoretical Biology. 524, 110729.","short":"K. Khudiakova, T.Y. Neretina, A.S. Kondrashov, Journal of Theoretical Biology 524 (2021)."},"month":"04","oa_version":"Preprint","publication_identifier":{"issn":["0022-5193"]},"status":"public","acknowledgement":"This work was supported by the Russian Science Foundation grant N 16-14-10173.","publication_status":"published","author":[{"orcid":"0000-0002-6246-1465","id":"4E6DC800-AE37-11E9-AC72-31CAE5697425","first_name":"Kseniia","full_name":"Khudiakova, Kseniia","last_name":"Khudiakova"},{"last_name":"Neretina","full_name":"Neretina, Tatiana Yu.","first_name":"Tatiana Yu."},{"last_name":"Kondrashov","full_name":"Kondrashov, Alexey S.","first_name":"Alexey S."}],"title":"Two linked loci under mutation-selection balance and Muller’s ratchet","_id":"9387","abstract":[{"lang":"eng","text":"We report the complete analysis of a deterministic model of deleterious mutations and negative selection against them at two haploid loci without recombination. As long as mutation is a weaker force than selection, mutant alleles remain rare at the only stable equilibrium, and otherwise, a variety of dynamics are possible. If the mutation-free genotype is absent, generally the only stable equilibrium is the one that corresponds to fixation of the mutant allele at the locus where it is less deleterious. This result suggests that fixation of a deleterious allele that follows a click of the Muller’s ratchet is governed by natural selection, instead of random drift."}],"doi":"10.1016/j.jtbi.2021.110729","intvolume":" 524","main_file_link":[{"open_access":"1","url":"https://www.biorxiv.org/content/10.1101/477489v1"}],"publisher":"Elsevier ","isi":1,"quality_controlled":"1","language":[{"iso":"eng"}],"type":"journal_article","department":[{"_id":"GradSch"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","date_published":"2021-04-24T00:00:00Z","external_id":{"isi":["000659161500002"]},"date_created":"2021-05-12T05:58:42Z","publication":"Journal of Theoretical Biology","date_updated":"2023-08-08T13:32:40Z","article_type":"original","article_number":"110729","oa":1,"year":"2021","keyword":["General Biochemistry","Genetics and Molecular Biology","Modelling and Simulation","Statistics and Probability","General Immunology and Microbiology","Applied Mathematics","General Agricultural and Biological Sciences","General Medicine"]},{"article_number":"e71575","article_type":"original","date_updated":"2023-08-14T11:50:50Z","publication":"eLife","keyword":["general immunology and microbiology","general biochemistry","genetics and molecular biology","general medicine","general neuroscience"],"year":"2021","oa":1,"type":"journal_article","quality_controlled":"1","language":[{"iso":"eng"}],"isi":1,"publisher":"eLife Sciences Publications","intvolume":" 10","date_created":"2021-11-18T06:59:45Z","date_published":"2021-11-17T00:00:00Z","external_id":{"isi":["000720945900001"]},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","department":[{"_id":"GaNo"}],"publication_status":"published","acknowledgement":"We thank Stuart Lipton and Nobuki Nakanishi for providing the Grin3a knockout mice, Beverly Davidson for the AAV-caRheb, Jose Esteban for help with behavioral and biochemical experiments, and Noelia Campillo, Rebeca Martínez-Turrillas, and Ana Navarro for expert technical help. Work was funded by the UTE project CIMA; fellowships from the Fundación Tatiana Pérez de Guzmán el Bueno, FEBS, and IBRO (to M.J.C.D.), Generalitat Valenciana (to O.E.-Z.), Juan de la Cierva (to L.G.R.), FPI-MINECO (to E.R.V., to S.N.) and Intertalentum postdoctoral program (to V.B.); ANR (GluBrain3A) and ERC Advanced Grants (#693021) (to P.P.); Ramón y Cajal program RYC2014-15784, RETOS-MINECO SAF2016-76565-R, ERANET-Neuron JTC 2019 ISCIII AC19/00077 FEDER funds (to R.A.); RETOS-MINECO SAF2017-87928-R (to A.B.); an NIH grant (NS76637) and UTHSC College of Medicine funds (to S.J.T.); and NARSAD Independent Investigator Award and grants from the MINECO (CSD2008-00005, SAF2013-48983R, SAF2016-80895-R), Generalitat Valenciana (PROMETEO 2019/020)(to I.P.O.) and Severo-Ochoa Excellence Awards (SEV-2013-0317, SEV-2017-0723).","status":"public","publication_identifier":{"issn":["2050-084X"]},"doi":"10.7554/elife.71575","abstract":[{"lang":"eng","text":"De novo protein synthesis is required for synapse modifications underlying stable memory encoding. Yet neurons are highly compartmentalized cells and how protein synthesis can be regulated at the synapse level is unknown. Here, we characterize neuronal signaling complexes formed by the postsynaptic scaffold GIT1, the mechanistic target of rapamycin (mTOR) kinase, and Raptor that couple synaptic stimuli to mTOR-dependent protein synthesis; and identify NMDA receptors containing GluN3A subunits as key negative regulators of GIT1 binding to mTOR. Disruption of GIT1/mTOR complexes by enhancing GluN3A expression or silencing GIT1 inhibits synaptic mTOR activation and restricts the mTOR-dependent translation of specific activity-regulated mRNAs. Conversely, GluN3A removal enables complex formation, potentiates mTOR-dependent protein synthesis, and facilitates the consolidation of associative and spatial memories in mice. The memory enhancement becomes evident with light or spaced training, can be achieved by selectively deleting GluN3A from excitatory neurons during adulthood, and does not compromise other aspects of cognition such as memory flexibility or extinction. Our findings provide mechanistic insight into synaptic translational control and reveal a potentially selective target for cognitive enhancement."}],"_id":"10301","title":"Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly","author":[{"first_name":"María J","full_name":"Conde-Dusman, María J","last_name":"Conde-Dusman"},{"full_name":"Dey, Partha N","last_name":"Dey","first_name":"Partha N"},{"first_name":"Óscar","full_name":"Elía-Zudaire, Óscar","last_name":"Elía-Zudaire"},{"first_name":"Luis E","id":"33D1B084-F248-11E8-B48F-1D18A9856A87","last_name":"Garcia Rabaneda","full_name":"Garcia Rabaneda, Luis E"},{"first_name":"Carmen","full_name":"García-Lira, Carmen","last_name":"García-Lira"},{"first_name":"Teddy","last_name":"Grand","full_name":"Grand, Teddy"},{"first_name":"Victor","last_name":"Briz","full_name":"Briz, Victor"},{"first_name":"Eric R","full_name":"Velasco, Eric R","last_name":"Velasco"},{"first_name":"Raül","last_name":"Andero Galí","full_name":"Andero Galí, Raül"},{"last_name":"Niñerola","full_name":"Niñerola, Sergio","first_name":"Sergio"},{"first_name":"Angel","last_name":"Barco","full_name":"Barco, Angel"},{"last_name":"Paoletti","full_name":"Paoletti, Pierre","first_name":"Pierre"},{"first_name":"John F","full_name":"Wesseling, John F","last_name":"Wesseling"},{"full_name":"Gardoni, Fabrizio","last_name":"Gardoni","first_name":"Fabrizio"},{"last_name":"Tavalin","full_name":"Tavalin, Steven J","first_name":"Steven J"},{"full_name":"Perez-Otaño, Isabel","last_name":"Perez-Otaño","first_name":"Isabel"}],"article_processing_charge":"No","volume":10,"has_accepted_license":"1","file":[{"file_id":"10302","date_created":"2021-11-18T07:02:02Z","success":1,"date_updated":"2021-11-18T07:02:02Z","access_level":"open_access","checksum":"59318e9e41507cec83c2f4070e6ad540","content_type":"application/pdf","file_name":"elife-71575-v1.pdf","file_size":2477302,"creator":"lgarciar","relation":"main_file"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"oa_version":"Published Version","ddc":["570"],"month":"11","file_date_updated":"2021-11-18T07:02:02Z","citation":{"mla":"Conde-Dusman, María J., et al. “Control of Protein Synthesis and Memory by GluN3A-NMDA Receptors through Inhibition of GIT1/MTORC1 Assembly.” ELife, vol. 10, e71575, eLife Sciences Publications, 2021, doi:10.7554/elife.71575.","chicago":"Conde-Dusman, María J, Partha N Dey, Óscar Elía-Zudaire, Luis E Garcia Rabaneda, Carmen García-Lira, Teddy Grand, Victor Briz, et al. “Control of Protein Synthesis and Memory by GluN3A-NMDA Receptors through Inhibition of GIT1/MTORC1 Assembly.” ELife. eLife Sciences Publications, 2021. https://doi.org/10.7554/elife.71575.","short":"M.J. Conde-Dusman, P.N. Dey, Ó. Elía-Zudaire, L.E. Garcia Rabaneda, C. García-Lira, T. Grand, V. Briz, E.R. Velasco, R. Andero Galí, S. Niñerola, A. Barco, P. Paoletti, J.F. Wesseling, F. Gardoni, S.J. Tavalin, I. Perez-Otaño, ELife 10 (2021).","ama":"Conde-Dusman MJ, Dey PN, Elía-Zudaire Ó, et al. Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly. eLife. 2021;10. doi:10.7554/elife.71575","ista":"Conde-Dusman MJ, Dey PN, Elía-Zudaire Ó, Garcia Rabaneda LE, García-Lira C, Grand T, Briz V, Velasco ER, Andero Galí R, Niñerola S, Barco A, Paoletti P, Wesseling JF, Gardoni F, Tavalin SJ, Perez-Otaño I. 2021. Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly. eLife. 10, e71575.","apa":"Conde-Dusman, M. J., Dey, P. N., Elía-Zudaire, Ó., Garcia Rabaneda, L. E., García-Lira, C., Grand, T., … Perez-Otaño, I. (2021). Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.71575","ieee":"M. J. Conde-Dusman et al., “Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly,” eLife, vol. 10. eLife Sciences Publications, 2021."},"day":"17"},{"year":"2020","keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"oa":1,"article_number":"e54383","article_type":"original","publication":"eLife","date_updated":"2022-07-18T08:30:37Z","date_published":"2020-09-08T00:00:00Z","external_id":{"pmid":["32896271"]},"extern":"1","date_created":"2022-04-07T07:43:48Z","scopus_import":"1","user_id":"72615eeb-f1f3-11ec-aa25-d4573ddc34fd","language":[{"iso":"eng"}],"type":"journal_article","quality_controlled":"1","publisher":"eLife Sciences Publications","intvolume":" 9","abstract":[{"text":"Vascular dysfunctions are a common feature of multiple age-related diseases. However, modeling healthy and pathological aging of the human vasculature represents an unresolved experimental challenge. Here, we generated induced vascular endothelial cells (iVECs) and smooth muscle cells (iSMCs) by direct reprogramming of healthy human fibroblasts from donors of different ages and Hutchinson-Gilford Progeria Syndrome (HGPS) patients. iVECs induced from old donors revealed upregulation of GSTM1 and PALD1, genes linked to oxidative stress, inflammation and endothelial junction stability, as vascular aging markers. A functional assay performed on PALD1 KD VECs demonstrated a recovery in vascular permeability. We found that iSMCs from HGPS donors overexpressed bone morphogenetic protein (BMP)−4, which plays a key role in both vascular calcification and endothelial barrier damage observed in HGPS. Strikingly, BMP4 concentrations are higher in serum from HGPS vs. age-matched mice. Furthermore, targeting BMP4 with blocking antibody recovered the functionality of the vascular barrier in vitro, hence representing a potential future therapeutic strategy to limit cardiovascular dysfunction in HGPS. These results show that iVECs and iSMCs retain disease-related signatures, allowing modeling of vascular aging and HGPS in vitro.","lang":"eng"}],"doi":"10.7554/elife.54383","title":"Direct reprogramming of human smooth muscle and vascular endothelial cells reveals defects associated with aging and Hutchinson-Gilford progeria syndrome","author":[{"first_name":"Simone","last_name":"Bersini","full_name":"Bersini, Simone"},{"first_name":"Roberta","full_name":"Schulte, Roberta","last_name":"Schulte"},{"first_name":"Ling","last_name":"Huang","full_name":"Huang, Ling"},{"last_name":"Tsai","full_name":"Tsai, Hannah","first_name":"Hannah"},{"full_name":"HETZER, Martin W","last_name":"HETZER","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","first_name":"Martin W","orcid":"0000-0002-2111-992X"}],"_id":"11055","publication_status":"published","status":"public","publication_identifier":{"issn":["2050-084X"]},"oa_version":"Published Version","citation":{"chicago":"Bersini, Simone, Roberta Schulte, Ling Huang, Hannah Tsai, and Martin Hetzer. “Direct Reprogramming of Human Smooth Muscle and Vascular Endothelial Cells Reveals Defects Associated with Aging and Hutchinson-Gilford Progeria Syndrome.” ELife. eLife Sciences Publications, 2020. https://doi.org/10.7554/elife.54383.","mla":"Bersini, Simone, et al. “Direct Reprogramming of Human Smooth Muscle and Vascular Endothelial Cells Reveals Defects Associated with Aging and Hutchinson-Gilford Progeria Syndrome.” ELife, vol. 9, e54383, eLife Sciences Publications, 2020, doi:10.7554/elife.54383.","apa":"Bersini, S., Schulte, R., Huang, L., Tsai, H., & Hetzer, M. (2020). Direct reprogramming of human smooth muscle and vascular endothelial cells reveals defects associated with aging and Hutchinson-Gilford progeria syndrome. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.54383","ieee":"S. Bersini, R. Schulte, L. Huang, H. Tsai, and M. Hetzer, “Direct reprogramming of human smooth muscle and vascular endothelial cells reveals defects associated with aging and Hutchinson-Gilford progeria syndrome,” eLife, vol. 9. eLife Sciences Publications, 2020.","ista":"Bersini S, Schulte R, Huang L, Tsai H, Hetzer M. 2020. Direct reprogramming of human smooth muscle and vascular endothelial cells reveals defects associated with aging and Hutchinson-Gilford progeria syndrome. eLife. 9, e54383.","short":"S. Bersini, R. Schulte, L. Huang, H. Tsai, M. Hetzer, ELife 9 (2020).","ama":"Bersini S, Schulte R, Huang L, Tsai H, Hetzer M. Direct reprogramming of human smooth muscle and vascular endothelial cells reveals defects associated with aging and Hutchinson-Gilford progeria syndrome. eLife. 2020;9. doi:10.7554/elife.54383"},"day":"08","file_date_updated":"2022-04-08T06:53:10Z","ddc":["570"],"month":"09","pmid":1,"has_accepted_license":"1","article_processing_charge":"No","volume":9,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"file":[{"file_id":"11132","date_created":"2022-04-08T06:53:10Z","success":1,"date_updated":"2022-04-08T06:53:10Z","access_level":"open_access","checksum":"f8b3821349a194050be02570d8fe7d4b","content_type":"application/pdf","file_name":"2020_eLife_Bersini.pdf","file_size":4399825,"creator":"dernst","relation":"main_file"}]},{"_id":"11060","author":[{"first_name":"Abigail","last_name":"Buchwalter","full_name":"Buchwalter, Abigail"},{"first_name":"Roberta","full_name":"Schulte, Roberta","last_name":"Schulte"},{"full_name":"Tsai, Hsiao","last_name":"Tsai","first_name":"Hsiao"},{"full_name":"Capitanio, Juliana","last_name":"Capitanio","first_name":"Juliana"},{"orcid":"0000-0002-2111-992X","first_name":"Martin W","id":"86c0d31b-b4eb-11ec-ac5a-eae7b2e135ed","last_name":"HETZER","full_name":"HETZER, Martin W"}],"title":"Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress","doi":"10.7554/elife.49796","abstract":[{"lang":"eng","text":"The inner nuclear membrane (INM) is a subdomain of the endoplasmic reticulum (ER) that is gated by the nuclear pore complex. It is unknown whether proteins of the INM and ER are degraded through shared or distinct pathways in mammalian cells. We applied dynamic proteomics to profile protein half-lives and report that INM and ER residents turn over at similar rates, indicating that the INM’s unique topology is not a barrier to turnover. Using a microscopy approach, we observed that the proteasome can degrade INM proteins in situ. However, we also uncovered evidence for selective, vesicular transport-mediated turnover of a single INM protein, emerin, that is potentiated by ER stress. Emerin is rapidly cleared from the INM by a mechanism that requires emerin’s LEM domain to mediate vesicular trafficking to lysosomes. This work demonstrates that the INM can be dynamically remodeled in response to environmental inputs."}],"publication_identifier":{"issn":["2050-084X"]},"publication_status":"published","status":"public","pmid":1,"month":"10","ddc":["570"],"file_date_updated":"2022-04-08T08:18:01Z","day":"10","citation":{"apa":"Buchwalter, A., Schulte, R., Tsai, H., Capitanio, J., & Hetzer, M. (2019). Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.49796","ieee":"A. Buchwalter, R. Schulte, H. Tsai, J. Capitanio, and M. Hetzer, “Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress,” eLife, vol. 8. eLife Sciences Publications, 2019.","ama":"Buchwalter A, Schulte R, Tsai H, Capitanio J, Hetzer M. Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress. eLife. 2019;8. doi:10.7554/elife.49796","short":"A. Buchwalter, R. Schulte, H. Tsai, J. Capitanio, M. Hetzer, ELife 8 (2019).","ista":"Buchwalter A, Schulte R, Tsai H, Capitanio J, Hetzer M. 2019. Selective clearance of the inner nuclear membrane protein emerin by vesicular transport during ER stress. eLife. 8, e49796.","mla":"Buchwalter, Abigail, et al. “Selective Clearance of the Inner Nuclear Membrane Protein Emerin by Vesicular Transport during ER Stress.” ELife, vol. 8, e49796, eLife Sciences Publications, 2019, doi:10.7554/elife.49796.","chicago":"Buchwalter, Abigail, Roberta Schulte, Hsiao Tsai, Juliana Capitanio, and Martin Hetzer. “Selective Clearance of the Inner Nuclear Membrane Protein Emerin by Vesicular Transport during ER Stress.” ELife. eLife Sciences Publications, 2019. https://doi.org/10.7554/elife.49796."},"oa_version":"Published Version","file":[{"date_created":"2022-04-08T08:18:01Z","file_id":"11138","date_updated":"2022-04-08T08:18:01Z","success":1,"checksum":"1e8672a1e9c3dc0a2d3d0dad89673616","content_type":"application/pdf","access_level":"open_access","file_size":6984654,"relation":"main_file","creator":"dernst","file_name":"2019_eLife_Buchwalter.pdf"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png","short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode"},"article_processing_charge":"No","volume":8,"has_accepted_license":"1","oa":1,"keyword":["General Immunology and Microbiology","General Biochemistry","Genetics and Molecular Biology","General Medicine","General Neuroscience"],"year":"2019","date_updated":"2023-05-31T06:36:22Z","publication":"eLife","article_type":"original","article_number":"e49796","related_material":{"record":[{"status":"public","relation":"research_data","id":"13079"}]},"user_id":"72615eeb-f1f3-11ec-aa25-d4573ddc34fd","scopus_import":"1","date_created":"2022-04-07T07:45:02Z","extern":"1","external_id":{"pmid":["31599721"]},"date_published":"2019-10-10T00:00:00Z","intvolume":" 8","publisher":"eLife Sciences Publications","type":"journal_article","language":[{"iso":"eng"}],"quality_controlled":"1"},{"publisher":"Institute of Science and Technology Austria","type":"dissertation","language":[{"iso":"eng"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","department":[{"_id":"MiSi"}],"date_created":"2019-09-19T08:19:44Z","date_published":"2019-07-24T00:00:00Z","date_updated":"2023-10-18T08:49:17Z","page":"171","related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"6328"},{"relation":"part_of_dissertation","status":"public","id":"15"},{"relation":"part_of_dissertation","status":"public","id":"6877"}],"link":[{"relation":"press_release","url":"https://ist.ac.at/en/news/feeling-like-a-cell/"}]},"oa":1,"keyword":["cell biology","immunology","leukocyte","migration","microfluidics"],"year":"2019","alternative_title":["ISTA Thesis"],"file":[{"date_created":"2019-10-15T05:28:42Z","file_id":"6950","embargo_to":"open_access","relation":"source_file","file_size":74735267,"creator":"akopf","file_name":"Kopf_PhD_Thesis.docx","date_updated":"2020-10-17T22:30:03Z","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","checksum":"00d100d6468e31e583051e0a006b640c","access_level":"closed"},{"file_id":"6951","date_created":"2019-10-15T05:28:47Z","file_name":"Kopf_PhD_Thesis1.pdf","relation":"main_file","file_size":52787224,"creator":"akopf","embargo":"2020-10-16","access_level":"open_access","content_type":"application/pdf","checksum":"5d1baa899993ae6ca81aebebe1797000","date_updated":"2020-10-17T22:30:03Z"}],"degree_awarded":"PhD","article_processing_charge":"No","has_accepted_license":"1","file_date_updated":"2020-10-17T22:30:03Z","month":"07","ddc":["570"],"day":"24","citation":{"apa":"Kopf, A. (2019). The implication of cytoskeletal dynamics on leukocyte migration. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6891","ieee":"A. Kopf, “The implication of cytoskeletal dynamics on leukocyte migration,” Institute of Science and Technology Austria, 2019.","ista":"Kopf A. 2019. The implication of cytoskeletal dynamics on leukocyte migration. Institute of Science and Technology Austria.","ama":"Kopf A. The implication of cytoskeletal dynamics on leukocyte migration. 2019. doi:10.15479/AT:ISTA:6891","short":"A. Kopf, The Implication of Cytoskeletal Dynamics on Leukocyte Migration, Institute of Science and Technology Austria, 2019.","mla":"Kopf, Aglaja. The Implication of Cytoskeletal Dynamics on Leukocyte Migration. Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6891.","chicago":"Kopf, Aglaja. “The Implication of Cytoskeletal Dynamics on Leukocyte Migration.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6891."},"oa_version":"Published Version","project":[{"_id":"265E2996-B435-11E9-9278-68D0E5697425","grant_number":"W01250-B20","call_identifier":"FWF","name":"Nano-Analytics of Cellular Systems"}],"publication_identifier":{"isbn":["978-3-99078-002-2"],"eissn":["2663-337X"]},"publication_status":"published","status":"public","_id":"6891","author":[{"first_name":"Aglaja","id":"31DAC7B6-F248-11E8-B48F-1D18A9856A87","last_name":"Kopf","full_name":"Kopf, Aglaja","orcid":"0000-0002-2187-6656"}],"supervisor":[{"first_name":"Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","last_name":"Sixt","full_name":"Sixt, Michael K","orcid":"0000-0002-6620-9179"}],"title":"The implication of cytoskeletal dynamics on leukocyte migration","doi":"10.15479/AT:ISTA:6891","abstract":[{"lang":"eng","text":"While cells of mesenchymal or epithelial origin perform their effector functions in a purely anchorage dependent manner, cells derived from the hematopoietic lineage are not committed to operate only within a specific niche. Instead, these cells are able to function autonomously of the molecular composition in a broad range of tissue compartments. By this means, cells of the hematopoietic lineage retain the capacity to disseminate into connective tissue and recirculate between organs, building the foundation for essential processes such as tissue regeneration or immune surveillance. \r\nCells of the immune system, specifically leukocytes, are extraordinarily good at performing this task. These cells are able to flexibly shift their mode of migration between an adhesion-mediated and an adhesion-independent manner, instantaneously accommodating for any changes in molecular composition of the external scaffold. The key component driving directed leukocyte migration is the chemokine receptor 7, which guides the cell along gradients of chemokine ligand. Therefore, the physical destination of migrating leukocytes is purely deterministic, i.e. given by global directional cues such as chemokine gradients. \r\nNevertheless, these cells typically reside in three-dimensional scaffolds of inhomogeneous complexity, raising the question whether cells are able to locally discriminate between multiple optional migration routes. Current literature provides evidence that leukocytes, specifically dendritic cells, do indeed probe their surrounding by virtue of multiple explorative protrusions. However, it remains enigmatic how these cells decide which one is the more favorable route to follow and what are the key players involved in performing this task. Due to the heterogeneous environment of most tissues, and the vast adaptability of migrating leukocytes, at this time it is not clear to what extent leukocytes are able to optimize their migratory strategy by adapting their level of adhesiveness. And, given the fact that leukocyte migration is characterized by branched cell shapes in combination with high migration velocities, it is reasonable to assume that these cells require fine tuned shape maintenance mechanisms that tightly coordinate protrusion and adhesion dynamics in a spatiotemporal manner. \r\nTherefore, this study aimed to elucidate how rapidly migrating leukocytes opt for an ideal migratory path while maintaining a continuous cell shape and balancing adhesive forces to efficiently navigate through complex microenvironments. \r\nThe results of this study unraveled a role for the microtubule cytoskeleton in promoting the decision making process during path finding and for the first time point towards a microtubule-mediated function in cell shape maintenance of highly ramified cells such as dendritic cells. Furthermore, we found that migrating low-adhesive leukocytes are able to instantaneously adapt to increased tensile load by engaging adhesion receptors. This response was only occurring tangential to the substrate while adhesive properties in the vertical direction were not increased. As leukocytes are primed for rapid migration velocities, these results demonstrate that leukocyte integrins are able to confer a high level of traction forces parallel to the cell membrane along the direction of migration without wasting energy in gluing the cell to the substrate. \r\nThus, the data in the here presented thesis provide new insights into the pivotal role of cytoskeletal dynamics and the mechanisms of force transduction during leukocyte migration. \r\nThereby the here presented results help to further define fundamental principles underlying leukocyte migration and open up potential therapeutic avenues of clinical relevance.\r\n"}]}]