[{"tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"acknowledgement":"This project has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement No 777364. This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA. The authors are very grateful to Martin Heinrich (Abbvie, Ludwigshafen, Germany) for the exceptional IT support and programming the EQIPD Planning Tool and the Creator Tool and to Dr Shai Silberberg (NINDS, USA), Dr. Renza Roncarati (PAASP Italy) and Dr Judith Homberg (Radboud University, Nijmegen) for highly stimulating contributions to the discussions and comments on earlier versions of this manuscript. We also wish to express our thanks to Dr. Sara Stöber (concentris research management GmbH, Fürstenfeldbruck, Germany) for excellent and continuous support of this project. Creation of the EQIPD Stakeholder group was supported by Noldus Information Technology bv (Wageningen, the Netherlands).","isi":1,"file_date_updated":"2021-06-28T11:35:30Z","intvolume":"        10","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","publication":"eLife","volume":10,"date_published":"2021-05-24T00:00:00Z","oa_version":"Published Version","publication_status":"published","publisher":"eLife Sciences Publications","language":[{"iso":"eng"}],"has_accepted_license":"1","citation":{"ieee":"A. Bespalov <i>et al.</i>, “Introduction to the EQIPD quality system,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021.","chicago":"Bespalov, Anton, René Bernard, Anja Gilis, Björn Gerlach, Javier Guillén, Vincent Castagné, Isabel A. Lefevre, et al. “Introduction to the EQIPD Quality System.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href=\"https://doi.org/10.7554/eLife.63294\">https://doi.org/10.7554/eLife.63294</a>.","ista":"Bespalov A, Bernard R, Gilis A, Gerlach B, Guillén J, Castagné V, Lefevre IA, Ducrey F, Monk L, Bongiovanni S, Altevogt B, Arroyo-Araujo M, Bikovski L, De Bruin N, Castaños-Vélez E, Dityatev A, Emmerich CH, Fares R, Ferland-Beckham C, Froger-Colléaux C, Gailus-Durner V, Hölter SM, Hofmann MC, Kabitzke P, Kas MJ, Kurreck C, Moser P, Pietraszek M, Popik P, Potschka H, Prado Montes De Oca E, Restivo L, Riedel G, Ritskes-Hoitinga M, Samardzic J, Schunn M, Stöger C, Voikar V, Vollert J, Wever KE, Wuyts K, Macleod MR, Dirnagl U, Steckler T. 2021. Introduction to the EQIPD quality system. eLife. 10.","short":"A. Bespalov, R. Bernard, A. Gilis, B. Gerlach, J. Guillén, V. Castagné, I.A. Lefevre, F. Ducrey, L. Monk, S. Bongiovanni, B. Altevogt, M. Arroyo-Araujo, L. Bikovski, N. De Bruin, E. Castaños-Vélez, A. Dityatev, C.H. Emmerich, R. Fares, C. Ferland-Beckham, C. Froger-Colléaux, V. Gailus-Durner, S.M. Hölter, M.C. Hofmann, P. Kabitzke, M.J. Kas, C. Kurreck, P. Moser, M. Pietraszek, P. Popik, H. Potschka, E. Prado Montes De Oca, L. Restivo, G. Riedel, M. Ritskes-Hoitinga, J. Samardzic, M. Schunn, C. Stöger, V. Voikar, J. Vollert, K.E. Wever, K. Wuyts, M.R. Macleod, U. Dirnagl, T. Steckler, ELife 10 (2021).","mla":"Bespalov, Anton, et al. “Introduction to the EQIPD Quality System.” <i>ELife</i>, vol. 10, eLife Sciences Publications, 2021, doi:<a href=\"https://doi.org/10.7554/eLife.63294\">10.7554/eLife.63294</a>.","ama":"Bespalov A, Bernard R, Gilis A, et al. Introduction to the EQIPD quality system. <i>eLife</i>. 2021;10. doi:<a href=\"https://doi.org/10.7554/eLife.63294\">10.7554/eLife.63294</a>","apa":"Bespalov, A., Bernard, R., Gilis, A., Gerlach, B., Guillén, J., Castagné, V., … Steckler, T. (2021). Introduction to the EQIPD quality system. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.63294\">https://doi.org/10.7554/eLife.63294</a>"},"publication_identifier":{"eissn":["2050-084X"]},"department":[{"_id":"PreCl"}],"pmid":1,"external_id":{"pmid":["34028353"],"isi":["000661272000001"]},"_id":"9607","date_updated":"2026-04-02T13:55:57Z","article_processing_charge":"No","type":"journal_article","oa":1,"file":[{"content_type":"application/pdf","date_created":"2021-06-28T11:35:30Z","file_name":"2021_ELife_Bespalov.pdf","success":1,"relation":"main_file","date_updated":"2021-06-28T11:35:30Z","access_level":"open_access","creator":"asandaue","file_size":2500720,"checksum":"885b746051a7a6b6e24e3d2781a48fde","file_id":"9609"}],"date_created":"2021-06-27T22:01:49Z","abstract":[{"text":"While high risk of failure is an inherent part of developing innovative therapies, it can be reduced by adherence to evidence-based rigorous research practices. Numerous analyses conducted to date have clearly identified measures that need to be taken to improve research rigor. Supported through the European Union's Innovative Medicines Initiative, the EQIPD consortium has developed a novel preclinical research quality system that can be applied in both public and private sectors and is free for anyone to use. The EQIPD Quality System was designed to be suited to boost innovation by ensuring the generation of robust and reliable preclinical data while being lean, effective and not becoming a burden that could negatively impact the freedom to explore scientific questions. EQIPD defines research quality as the extent to which research data are fit for their intended use. Fitness, in this context, is defined by the stakeholders, who are the scientists directly involved in the research, but also their funders, sponsors, publishers, research tool manufacturers and collaboration partners such as peers in a multi-site research project. The essence of the EQIPD Quality System is the set of 18 core requirements that can be addressed flexibly, according to user-specific needs and following a user-defined trajectory. The EQIPD Quality System proposes guidance on expectations for quality-related measures, defines criteria for adequate processes (i.e., performance standards) and provides examples of how such measures can be developed and implemented. However, it does not prescribe any pre-determined solutions. EQIPD has also developed tools (for optional use) to support users in implementing the system and assessment services for those research units that successfully implement the quality system and seek formal accreditation. Building upon the feedback from users and continuous improvement, a sustainable EQIPD Quality System will ultimately serve the entire community of scientists conducting non-regulated preclinical research, by helping them generate reliable data that are fit for their intended use.","lang":"eng"}],"status":"public","quality_controlled":"1","article_type":"original","day":"24","scopus_import":"1","author":[{"last_name":"Bespalov","first_name":"Anton","full_name":"Bespalov, Anton"},{"last_name":"Bernard","first_name":"René","full_name":"Bernard, René"},{"full_name":"Gilis, Anja","last_name":"Gilis","first_name":"Anja"},{"first_name":"Björn","last_name":"Gerlach","full_name":"Gerlach, Björn"},{"first_name":"Javier","last_name":"Guillén","full_name":"Guillén, Javier"},{"first_name":"Vincent","last_name":"Castagné","full_name":"Castagné, Vincent"},{"first_name":"Isabel A.","last_name":"Lefevre","full_name":"Lefevre, Isabel A."},{"last_name":"Ducrey","first_name":"Fiona","full_name":"Ducrey, Fiona"},{"full_name":"Monk, Lee","last_name":"Monk","first_name":"Lee"},{"full_name":"Bongiovanni, Sandrine","last_name":"Bongiovanni","first_name":"Sandrine"},{"first_name":"Bruce","last_name":"Altevogt","full_name":"Altevogt, Bruce"},{"first_name":"María","last_name":"Arroyo-Araujo","full_name":"Arroyo-Araujo, María"},{"full_name":"Bikovski, Lior","last_name":"Bikovski","first_name":"Lior"},{"full_name":"De Bruin, Natasja","first_name":"Natasja","last_name":"De Bruin"},{"last_name":"Castaños-Vélez","first_name":"Esmeralda","full_name":"Castaños-Vélez, Esmeralda"},{"last_name":"Dityatev","first_name":"Alexander","full_name":"Dityatev, Alexander"},{"last_name":"Emmerich","first_name":"Christoph H.","full_name":"Emmerich, Christoph H."},{"last_name":"Fares","first_name":"Raafat","full_name":"Fares, Raafat"},{"full_name":"Ferland-Beckham, Chantelle","first_name":"Chantelle","last_name":"Ferland-Beckham"},{"full_name":"Froger-Colléaux, Christelle","first_name":"Christelle","last_name":"Froger-Colléaux"},{"first_name":"Valerie","last_name":"Gailus-Durner","full_name":"Gailus-Durner, Valerie"},{"full_name":"Hölter, Sabine M.","first_name":"Sabine M.","last_name":"Hölter"},{"last_name":"Hofmann","first_name":"Martine Cj","full_name":"Hofmann, Martine Cj"},{"full_name":"Kabitzke, Patricia","first_name":"Patricia","last_name":"Kabitzke"},{"full_name":"Kas, Martien Jh","first_name":"Martien Jh","last_name":"Kas"},{"last_name":"Kurreck","first_name":"Claudia","full_name":"Kurreck, Claudia"},{"last_name":"Moser","first_name":"Paul","full_name":"Moser, Paul"},{"last_name":"Pietraszek","first_name":"Malgorzata","full_name":"Pietraszek, Malgorzata"},{"full_name":"Popik, Piotr","last_name":"Popik","first_name":"Piotr"},{"full_name":"Potschka, Heidrun","first_name":"Heidrun","last_name":"Potschka"},{"full_name":"Prado Montes De Oca, Ernesto","first_name":"Ernesto","last_name":"Prado Montes De Oca"},{"full_name":"Restivo, Leonardo","last_name":"Restivo","first_name":"Leonardo"},{"full_name":"Riedel, Gernot","last_name":"Riedel","first_name":"Gernot"},{"last_name":"Ritskes-Hoitinga","first_name":"Merel","full_name":"Ritskes-Hoitinga, Merel"},{"last_name":"Samardzic","first_name":"Janko","full_name":"Samardzic, Janko"},{"id":"4272DB4A-F248-11E8-B48F-1D18A9856A87","full_name":"Schunn, Michael","last_name":"Schunn","first_name":"Michael","orcid":"0000-0003-4326-5300"},{"full_name":"Stöger, Claudia","first_name":"Claudia","last_name":"Stöger"},{"last_name":"Voikar","first_name":"Vootele","full_name":"Voikar, Vootele"},{"full_name":"Vollert, Jan","last_name":"Vollert","first_name":"Jan"},{"full_name":"Wever, Kimberley E.","first_name":"Kimberley E.","last_name":"Wever"},{"first_name":"Kathleen","last_name":"Wuyts","full_name":"Wuyts, Kathleen"},{"full_name":"Macleod, Malcolm R.","last_name":"Macleod","first_name":"Malcolm R."},{"full_name":"Dirnagl, Ulrich","last_name":"Dirnagl","first_name":"Ulrich"},{"first_name":"Thomas","last_name":"Steckler","full_name":"Steckler, Thomas"}],"doi":"10.7554/eLife.63294","year":"2021","title":"Introduction to the EQIPD quality system","month":"05","ddc":["570"]},{"status":"public","quality_controlled":"1","type":"journal_article","oa":1,"file":[{"relation":"main_file","creator":"dernst","access_level":"open_access","date_updated":"2021-03-22T08:50:33Z","checksum":"20ccf4dfe46c48cf986794c8bf4fd1cb","file_size":9259690,"file_id":"9271","file_name":"2021_eLife_Hankeova.pdf","date_created":"2021-03-22T08:50:33Z","content_type":"application/pdf","success":1}],"date_created":"2021-03-14T23:01:34Z","abstract":[{"text":"Organ function depends on tissues adopting the correct architecture. However, insights into organ architecture are currently hampered by an absence of standardized quantitative 3D analysis. We aimed to develop a robust technology to visualize, digitalize, and segment the architecture of two tubular systems in 3D: double resin casting micro computed tomography (DUCT). As proof of principle, we applied DUCT to a mouse model for Alagille syndrome (Jag1Ndr/Ndr mice), characterized by intrahepatic bile duct paucity, that can spontaneously generate a biliary system in adulthood. DUCT identified increased central biliary branching and peripheral bile duct tortuosity as two compensatory processes occurring in distinct regions of Jag1Ndr/Ndr liver, leading to full reconstitution of wild-type biliary volume and phenotypic recovery. DUCT is thus a powerful new technology for 3D analysis, which can reveal novel phenotypes and provide a standardized method of defining liver architecture in mouse models.","lang":"eng"}],"title":"DUCT reveals architectural mechanisms contributing to bile duct recovery in a mouse model for alagille syndrome","month":"02","ddc":["570"],"article_type":"original","article_number":"e60916","day":"26","scopus_import":"1","project":[{"_id":"05943252-7A3F-11EA-A408-12923DDC885E","call_identifier":"H2020","grant_number":"851288","name":"Design Principles of Branching Morphogenesis"}],"author":[{"full_name":"Hankeova, Simona","first_name":"Simona","last_name":"Hankeova"},{"full_name":"Salplachta, Jakub","first_name":"Jakub","last_name":"Salplachta"},{"first_name":"Tomas","last_name":"Zikmund","full_name":"Zikmund, Tomas"},{"full_name":"Kavkova, Michaela","first_name":"Michaela","last_name":"Kavkova"},{"first_name":"Noémi","last_name":"Van Hul","full_name":"Van Hul, Noémi"},{"last_name":"Brinek","first_name":"Adam","full_name":"Brinek, Adam"},{"first_name":"Veronika","last_name":"Smekalova","full_name":"Smekalova, Veronika"},{"full_name":"Laznovsky, Jakub","first_name":"Jakub","last_name":"Laznovsky"},{"full_name":"Dawit, Feven","last_name":"Dawit","first_name":"Feven"},{"full_name":"Jaros, Josef","last_name":"Jaros","first_name":"Josef"},{"full_name":"Bryja, Vítězslav","last_name":"Bryja","first_name":"Vítězslav"},{"full_name":"Lendahl, Urban","last_name":"Lendahl","first_name":"Urban"},{"last_name":"Ellis","first_name":"Ewa","full_name":"Ellis, Ewa"},{"last_name":"Nemeth","first_name":"Antal","full_name":"Nemeth, Antal"},{"full_name":"Fischler, Björn","first_name":"Björn","last_name":"Fischler"},{"id":"3A9DB764-F248-11E8-B48F-1D18A9856A87","full_name":"Hannezo, Edouard B","first_name":"Edouard B","last_name":"Hannezo","orcid":"0000-0001-6005-1561"},{"first_name":"Jozef","last_name":"Kaiser","full_name":"Kaiser, Jozef"},{"full_name":"Andersson, Emma Rachel","last_name":"Andersson","first_name":"Emma Rachel"}],"doi":"10.7554/eLife.60916","year":"2021","volume":10,"date_published":"2021-02-26T00:00:00Z","ec_funded":1,"oa_version":"Published Version","publication_status":"published","publisher":"eLife Sciences Publications","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"acknowledgement":"Work in ERA lab is supported by the Swedish Research Council, the Center of Innovative Medicine (CIMED) Grant, Karolinska Institutet, and the Heart and Lung Foundation, and\r\nthe Daniel Alagille Award from the European Association for the Study of the Liver. One project in ERA lab is funded by ModeRNA, unrelated to this project. The funders have no role in the design or interpretation of the work. SH has been supported by a KI-MU PhD student program, and by a Wera Ekstro¨m Foundation Scholarship. We are grateful for support from Tornspiran foundation to NVH. JK: This research was carried out under the project CEITEC 2020 (LQ1601) with financial support from the Ministry of Education, Youth and Sports of the Czech Republic under the National Sustainability Programme II and CzechNanoLab Research Infrastructure supported by MEYS CR (LM2018110) . UL: The financial support from the Swedish Research Council and ICMC (Integrated CardioMetabolic Center) is acknowledged. JJ: The work was supported by the Grant Agency of Masaryk University (project no. MUNI/A/1565/2018). We thank Kari Huppert and Stacey Huppert for their expertise and help regarding bile duct cannulation and their laboratory hospitality. We also thank Nadja Schultz and Charlotte L Mattsson for their help with common bile duct cannulation. We thank Daniel Holl for his help with trachea cannulation. We thank Nikos Papadogiannakis for his assistance with mild Alagille biopsy samples and discussion. We thank Karolinska Biomedicum Imaging Core, especially Shigeaki Kanatani for his help with image analysis. We thank Jan Masek and Carolina Gutierrez for their scientific input in manuscript writing. We thank Peter Ranefall and the BioImage Informatics (SciLife national facility) for their help writing parts of the MATLAB pipeline.\r\nThe TROMA-III antibody developed by Rolf Kemler was obtained from the Developmental Studies Hybridoma (DSHB) Bank developed under the auspices of NICHD and maintained by The University of Iowa, Department of Biological Sciences, Iowa City, IA52242. We thank Goncalo M Brito for all illustrations. This work was supported by the European Union (European Research Council Starting grant 851288 to E.H.).","isi":1,"file_date_updated":"2021-03-22T08:50:33Z","intvolume":"        10","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","publication":"eLife","_id":"9244","date_updated":"2026-04-02T14:00:00Z","article_processing_charge":"No","language":[{"iso":"eng"}],"has_accepted_license":"1","citation":{"apa":"Hankeova, S., Salplachta, J., Zikmund, T., Kavkova, M., Van Hul, N., Brinek, A., … Andersson, E. R. (2021). DUCT reveals architectural mechanisms contributing to bile duct recovery in a mouse model for alagille syndrome. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.60916\">https://doi.org/10.7554/eLife.60916</a>","ista":"Hankeova S, Salplachta J, Zikmund T, Kavkova M, Van Hul N, Brinek A, Smekalova V, Laznovsky J, Dawit F, Jaros J, Bryja V, Lendahl U, Ellis E, Nemeth A, Fischler B, Hannezo EB, Kaiser J, Andersson ER. 2021. DUCT reveals architectural mechanisms contributing to bile duct recovery in a mouse model for alagille syndrome. eLife. 10, e60916.","short":"S. Hankeova, J. Salplachta, T. Zikmund, M. Kavkova, N. Van Hul, A. Brinek, V. Smekalova, J. Laznovsky, F. Dawit, J. Jaros, V. Bryja, U. Lendahl, E. Ellis, A. Nemeth, B. Fischler, E.B. Hannezo, J. Kaiser, E.R. Andersson, ELife 10 (2021).","mla":"Hankeova, Simona, et al. “DUCT Reveals Architectural Mechanisms Contributing to Bile Duct Recovery in a Mouse Model for Alagille Syndrome.” <i>ELife</i>, vol. 10, e60916, eLife Sciences Publications, 2021, doi:<a href=\"https://doi.org/10.7554/eLife.60916\">10.7554/eLife.60916</a>.","ama":"Hankeova S, Salplachta J, Zikmund T, et al. DUCT reveals architectural mechanisms contributing to bile duct recovery in a mouse model for alagille syndrome. <i>eLife</i>. 2021;10. doi:<a href=\"https://doi.org/10.7554/eLife.60916\">10.7554/eLife.60916</a>","ieee":"S. Hankeova <i>et al.</i>, “DUCT reveals architectural mechanisms contributing to bile duct recovery in a mouse model for alagille syndrome,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021.","chicago":"Hankeova, Simona, Jakub Salplachta, Tomas Zikmund, Michaela Kavkova, Noémi Van Hul, Adam Brinek, Veronika Smekalova, et al. “DUCT Reveals Architectural Mechanisms Contributing to Bile Duct Recovery in a Mouse Model for Alagille Syndrome.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href=\"https://doi.org/10.7554/eLife.60916\">https://doi.org/10.7554/eLife.60916</a>."},"publication_identifier":{"eissn":["2050-084X"]},"pmid":1,"department":[{"_id":"EdHa"}],"external_id":{"pmid":["33635272"],"isi":["000625357100001"]}},{"publisher":"eLife Sciences Publications","publication_status":"published","date_published":"2021-04-29T00:00:00Z","volume":10,"oa_version":"Published Version","ec_funded":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","file_date_updated":"2021-05-31T09:43:09Z","intvolume":"        10","publication":"eLife","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"isi":1,"acknowledgement":"We are grateful to Akari Hagiwara and Toshihisa Ohtsuka for CAST antibody, and Masahiko Watanabe for neurexin antibody. We thank David Adams for kindly providing the stable Cav2.3 cell line. Cav2.3 KO mice were kindly provided by Tsutomu Tanabe. This project has received funding from the European Research Council (ERC) and European Commission (EC), under the European Union’s Horizon 2020 research and innovation programme (ERC grant agreement no. 694539 to Ryuichi Shigemoto, no. 692692 to Peter Jonas, and the Marie Skłodowska-Curie grant agreement no. 665385 to Cihan Önal), the Swiss National Science Foundation Grant 31003A-172881 to Bernhard Bettler and Deutsche Forschungsgemeinschaft (For 2143) and BIOSS-2 to Akos Kulik.","_id":"9437","article_processing_charge":"No","date_updated":"2026-04-30T22:30:40Z","department":[{"_id":"RySh"},{"_id":"PeJo"}],"pmid":1,"citation":{"ista":"Bhandari P, Vandael DH, Fernández-Fernández D, Fritzius T, Kleindienst D, Önal C, Montanaro-Punzengruber J-C, Gassmann M, Jonas PM, Kulik A, Bettler B, Shigemoto R, Koppensteiner P. 2021. GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals. eLife. 10, e68274.","short":"P. Bhandari, D.H. Vandael, D. Fernández-Fernández, T. Fritzius, D. Kleindienst, C. Önal, J.-C. Montanaro-Punzengruber, M. Gassmann, P.M. Jonas, A. Kulik, B. Bettler, R. Shigemoto, P. Koppensteiner, ELife 10 (2021).","ama":"Bhandari P, Vandael DH, Fernández-Fernández D, et al. GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals. <i>eLife</i>. 2021;10. doi:<a href=\"https://doi.org/10.7554/ELIFE.68274\">10.7554/ELIFE.68274</a>","mla":"Bhandari, Pradeep, et al. “GABAB Receptor Auxiliary Subunits Modulate Cav2.3-Mediated Release from Medial Habenula Terminals.” <i>ELife</i>, vol. 10, e68274, eLife Sciences Publications, 2021, doi:<a href=\"https://doi.org/10.7554/ELIFE.68274\">10.7554/ELIFE.68274</a>.","apa":"Bhandari, P., Vandael, D. H., Fernández-Fernández, D., Fritzius, T., Kleindienst, D., Önal, C., … Koppensteiner, P. (2021). GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/ELIFE.68274\">https://doi.org/10.7554/ELIFE.68274</a>","ieee":"P. Bhandari <i>et al.</i>, “GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals,” <i>eLife</i>, vol. 10. eLife Sciences Publications, 2021.","chicago":"Bhandari, Pradeep, David H Vandael, Diego Fernández-Fernández, Thorsten Fritzius, David Kleindienst, Cihan Önal, Jacqueline-Claire Montanaro-Punzengruber, et al. “GABAB Receptor Auxiliary Subunits Modulate Cav2.3-Mediated Release from Medial Habenula Terminals.” <i>ELife</i>. eLife Sciences Publications, 2021. <a href=\"https://doi.org/10.7554/ELIFE.68274\">https://doi.org/10.7554/ELIFE.68274</a>."},"publication_identifier":{"eissn":["2050-084X"]},"external_id":{"isi":["000651761700001"],"pmid":["33913808"]},"has_accepted_license":"1","language":[{"iso":"eng"}],"status":"public","quality_controlled":"1","date_created":"2021-05-30T22:01:23Z","abstract":[{"text":"The synaptic connection from medial habenula (MHb) to interpeduncular nucleus (IPN) is critical for emotion-related behaviors and uniquely expresses R-type Ca2+ channels (Cav2.3) and auxiliary GABAB receptor (GBR) subunits, the K+-channel tetramerization domain-containing proteins (KCTDs). Activation of GBRs facilitates or inhibits transmitter release from MHb terminals depending on the IPN subnucleus, but the role of KCTDs is unknown. We therefore examined the localization and function of Cav2.3, GBRs, and KCTDs in this pathway in mice. We show in heterologous cells that KCTD8 and KCTD12b directly bind to Cav2.3 and that KCTD8 potentiates Cav2.3 currents in the absence of GBRs. In the rostral IPN, KCTD8, KCTD12b, and Cav2.3 co-localize at the presynaptic active zone. Genetic deletion indicated a bidirectional modulation of Cav2.3-mediated release by these KCTDs with a compensatory increase of KCTD8 in the active zone in KCTD12b-deficient mice. The interaction of Cav2.3 with KCTDs therefore scales synaptic strength independent of GBR activation.","lang":"eng"}],"type":"journal_article","file":[{"file_name":"2021_eLife_Bhandari.pdf","content_type":"application/pdf","date_created":"2021-05-31T09:43:09Z","success":1,"checksum":"6ebcb79999f889766f7cd79ee134ad28","file_size":8174719,"file_id":"9440","relation":"main_file","access_level":"open_access","creator":"cziletti","date_updated":"2021-05-31T09:43:09Z"}],"oa":1,"related_material":{"link":[{"url":"https://doi.org/10.1101/2020.04.16.045112","relation":"earlier_version"}],"record":[{"relation":"dissertation_contains","status":"public","id":"19271"},{"relation":"dissertation_contains","status":"public","id":"9562"}]},"ddc":["570"],"title":"GABAB receptor auxiliary subunits modulate Cav2.3-mediated release from medial habenula terminals","month":"04","scopus_import":"1","day":"29","year":"2021","doi":"10.7554/ELIFE.68274","author":[{"orcid":"0000-0003-0863-4481","first_name":"Pradeep","last_name":"Bhandari","id":"45EDD1BC-F248-11E8-B48F-1D18A9856A87","full_name":"Bhandari, Pradeep"},{"first_name":"David H","last_name":"Vandael","orcid":"0000-0001-7577-1676","full_name":"Vandael, David H","id":"3AE48E0A-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Diego","last_name":"Fernández-Fernández","full_name":"Fernández-Fernández, Diego"},{"first_name":"Thorsten","last_name":"Fritzius","full_name":"Fritzius, Thorsten"},{"last_name":"Kleindienst","first_name":"David","full_name":"Kleindienst, David","id":"42E121A4-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Hüseyin C","last_name":"Önal","orcid":"0000-0002-2771-2011","full_name":"Önal, Hüseyin C","id":"4659D740-F248-11E8-B48F-1D18A9856A87"},{"id":"3786AB44-F248-11E8-B48F-1D18A9856A87","full_name":"Montanaro-Punzengruber, Jacqueline-Claire","first_name":"Jacqueline-Claire","last_name":"Montanaro-Punzengruber"},{"last_name":"Gassmann","first_name":"Martin","full_name":"Gassmann, Martin"},{"last_name":"Jonas","first_name":"Peter M","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Kulik, Akos","first_name":"Akos","last_name":"Kulik"},{"last_name":"Bettler","first_name":"Bernhard","full_name":"Bettler, Bernhard"},{"orcid":"0000-0001-8761-9444","last_name":"Shigemoto","first_name":"Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","full_name":"Shigemoto, Ryuichi"},{"full_name":"Koppensteiner, Peter","id":"3B8B25A8-F248-11E8-B48F-1D18A9856A87","first_name":"Peter","last_name":"Koppensteiner","orcid":"0000-0002-3509-1948"}],"project":[{"name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","_id":"25CA28EA-B435-11E9-9278-68D0E5697425","grant_number":"694539","call_identifier":"H2020"},{"grant_number":"692692","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glutamatergic synapse"},{"call_identifier":"H2020","grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","name":"International IST Doctoral Program"}],"article_type":"original","article_number":"e68274"},{"status":"public","quality_controlled":"1","type":"journal_article","oa":1,"file":[{"relation":"main_file","access_level":"open_access","creator":"cziletti","date_updated":"2020-10-27T11:37:32Z","checksum":"c4300ddcd93ed03fc9c6cdf1f77890be","file_size":17355867,"file_id":"8709","file_name":"2020_eLife_Gonçalves.pdf","content_type":"application/pdf","date_created":"2020-10-27T11:37:32Z","success":1}],"date_created":"2020-07-16T12:26:04Z","abstract":[{"text":"Mechanistic modeling in neuroscience aims to explain observed phenomena in terms of underlying causes. However, determining which model parameters agree with complex and stochastic neural data presents a significant challenge. We address this challenge with a machine learning tool which uses deep neural density estimators—trained using model simulations—to carry out Bayesian inference and retrieve the full space of parameters compatible with raw data or selected data features. Our method is scalable in parameters and data features and can rapidly analyze new data after initial training. We demonstrate the power and flexibility of our approach on receptive fields, ion channels, and Hodgkin–Huxley models. We also characterize the space of circuit configurations giving rise to rhythmic activity in the crustacean stomatogastric ganglion, and use these results to derive hypotheses for underlying compensation mechanisms. Our approach will help close the gap between data-driven and theory-driven models of neural dynamics.","lang":"eng"}],"title":"Training deep neural density estimators to identify mechanistic models of neural dynamics","month":"09","ddc":["570"],"article_type":"original","article_number":"e56261","scopus_import":"1","day":"17","doi":"10.7554/eLife.56261","year":"2020","author":[{"orcid":"0000-0002-6987-4836","first_name":"Pedro J.","last_name":"Gonçalves","full_name":"Gonçalves, Pedro J."},{"last_name":"Lueckmann","first_name":"Jan-Matthis","orcid":"0000-0003-4320-4663","full_name":"Lueckmann, Jan-Matthis"},{"orcid":"0000-0002-3573-0404","first_name":"Michael","last_name":"Deistler","full_name":"Deistler, Michael"},{"full_name":"Nonnenmacher, Marcel","first_name":"Marcel","last_name":"Nonnenmacher","orcid":"0000-0001-6044-6627"},{"orcid":"0000-0002-8528-6858","last_name":"Öcal","first_name":"Kaan","full_name":"Öcal, Kaan"},{"full_name":"Bassetto, Giacomo","last_name":"Bassetto","first_name":"Giacomo"},{"id":"BA06AFEE-A4BA-11EA-AE5C-14673DDC885E","full_name":"Chintaluri, Chaitanya","orcid":"0000-0003-4252-1608","first_name":"Chaitanya","last_name":"Chintaluri"},{"full_name":"Podlaski, William F.","orcid":"0000-0001-6619-7502","first_name":"William F.","last_name":"Podlaski"},{"orcid":"0000-0003-0807-0823","last_name":"Haddad","first_name":"Sara A.","full_name":"Haddad, Sara A."},{"full_name":"Vogels, Tim P","id":"CB6FF8D2-008F-11EA-8E08-2637E6697425","orcid":"0000-0003-3295-6181","last_name":"Vogels","first_name":"Tim P"},{"full_name":"Greenberg, David S.","last_name":"Greenberg","first_name":"David S."},{"orcid":"0000-0001-5154-8912","last_name":"Macke","first_name":"Jakob H.","full_name":"Macke, Jakob H."}],"project":[{"name":"Learning the shape of synaptic plasticity rules for neuronal architectures and function through machine learning.","_id":"0aacfa84-070f-11eb-9043-d7eb2c709234","grant_number":"819603","call_identifier":"H2020"}],"date_published":"2020-09-17T00:00:00Z","volume":9,"oa_version":"Published Version","ec_funded":1,"publisher":"eLife Sciences Publications","publication_status":"published","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"isi":1,"acknowledgement":"We thank Mahmood S Hoseini and Michael Stryker for sharing their data for Figure 2, and Philipp Berens, Sean Bittner, Jan Boelts, John Cunningham, Richard Gao, Scott Linderman, Eve Marder, Iain Murray, George Papamakarios, Astrid Prinz, Auguste Schulz and Srinivas Turaga for discussions and/or comments on the manuscript. This work was supported by the German Research Foundation (DFG) through SFB 1233 ‘Robust Vision’, (276693517), SFB 1089 ‘Synaptic Microcircuits’, SPP 2041 ‘Computational Connectomics’ and Germany's Excellence Strategy – EXC-Number 2064/1 – Project number 390727645 and the German Federal Ministry of Education and Research (BMBF, project ‘ADIMEM’, FKZ 01IS18052 A-D) to JHM, a Sir Henry Dale Fellowship by the Wellcome Trust and the Royal Society (WT100000; WFP and TPV), a Wellcome Trust Senior Research Fellowship (214316/Z/18/Z; TPV), a ERC Consolidator Grant (SYNAPSEEK; WPF and CC), and a UK Research and Innovation, Biotechnology and Biological Sciences Research Council (CC, UKRI-BBSRC BB/N019512/1). We gratefully acknowledge the Leibniz Supercomputing Centre for funding this project by providing computing time on its Linux-Cluster.","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","file_date_updated":"2020-10-27T11:37:32Z","intvolume":"         9","publication":"eLife","_id":"8127","article_processing_charge":"No","date_updated":"2025-04-14T07:54:31Z","has_accepted_license":"1","language":[{"iso":"eng"}],"pmid":1,"department":[{"_id":"TiVo"}],"publication_identifier":{"eissn":["2050-084X"]},"citation":{"chicago":"Gonçalves, Pedro J., Jan-Matthis Lueckmann, Michael Deistler, Marcel Nonnenmacher, Kaan Öcal, Giacomo Bassetto, Chaitanya Chintaluri, et al. “Training Deep Neural Density Estimators to Identify Mechanistic Models of Neural Dynamics.” <i>ELife</i>. eLife Sciences Publications, 2020. <a href=\"https://doi.org/10.7554/eLife.56261\">https://doi.org/10.7554/eLife.56261</a>.","ieee":"P. J. Gonçalves <i>et al.</i>, “Training deep neural density estimators to identify mechanistic models of neural dynamics,” <i>eLife</i>, vol. 9. eLife Sciences Publications, 2020.","mla":"Gonçalves, Pedro J., et al. “Training Deep Neural Density Estimators to Identify Mechanistic Models of Neural Dynamics.” <i>ELife</i>, vol. 9, e56261, eLife Sciences Publications, 2020, doi:<a href=\"https://doi.org/10.7554/eLife.56261\">10.7554/eLife.56261</a>.","ama":"Gonçalves PJ, Lueckmann J-M, Deistler M, et al. Training deep neural density estimators to identify mechanistic models of neural dynamics. <i>eLife</i>. 2020;9. doi:<a href=\"https://doi.org/10.7554/eLife.56261\">10.7554/eLife.56261</a>","short":"P.J. Gonçalves, J.-M. Lueckmann, M. Deistler, M. Nonnenmacher, K. Öcal, G. Bassetto, C. Chintaluri, W.F. Podlaski, S.A. Haddad, T.P. Vogels, D.S. Greenberg, J.H. Macke, ELife 9 (2020).","ista":"Gonçalves PJ, Lueckmann J-M, Deistler M, Nonnenmacher M, Öcal K, Bassetto G, Chintaluri C, Podlaski WF, Haddad SA, Vogels TP, Greenberg DS, Macke JH. 2020. Training deep neural density estimators to identify mechanistic models of neural dynamics. eLife. 9, e56261.","apa":"Gonçalves, P. J., Lueckmann, J.-M., Deistler, M., Nonnenmacher, M., Öcal, K., Bassetto, G., … Macke, J. H. (2020). Training deep neural density estimators to identify mechanistic models of neural dynamics. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.56261\">https://doi.org/10.7554/eLife.56261</a>"},"external_id":{"pmid":["32940606"],"isi":["000584989400001"]}},{"doi":"10.7554/eLife.52067","year":"2020","author":[{"last_name":"Narasimhan","first_name":"Madhumitha","orcid":"0000-0002-8600-0671","id":"44BF24D0-F248-11E8-B48F-1D18A9856A87","full_name":"Narasimhan, Madhumitha"},{"full_name":"Johnson, Alexander J","id":"46A62C3A-F248-11E8-B48F-1D18A9856A87","last_name":"Johnson","first_name":"Alexander J","orcid":"0000-0002-2739-8843"},{"full_name":"Prizak, Roshan","id":"4456104E-F248-11E8-B48F-1D18A9856A87","last_name":"Prizak","first_name":"Roshan"},{"full_name":"Kaufmann, Walter","id":"3F99E422-F248-11E8-B48F-1D18A9856A87","last_name":"Kaufmann","first_name":"Walter","orcid":"0000-0001-9735-5315"},{"id":"2DE75584-F248-11E8-B48F-1D18A9856A87","full_name":"Tan, Shutang","orcid":"0000-0002-0471-8285","first_name":"Shutang","last_name":"Tan"},{"full_name":"Casillas Perez, Barbara E","id":"351ED2AA-F248-11E8-B48F-1D18A9856A87","first_name":"Barbara E","last_name":"Casillas Perez"},{"id":"4159519E-F248-11E8-B48F-1D18A9856A87","full_name":"Friml, Jiří","orcid":"0000-0002-8302-7596","last_name":"Friml","first_name":"Jiří"}],"project":[{"name":"Tracing Evolution of Auxin Transport and Polarity in Plants","call_identifier":"H2020","grant_number":"742985","_id":"261099A6-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","grant_number":"I03630","_id":"26538374-B435-11E9-9278-68D0E5697425","name":"Molecular mechanisms of endocytic cargo recognition in plants"}],"scopus_import":"1","day":"23","article_number":"e52067","article_type":"original","ddc":["570","580"],"month":"01","title":"Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants","abstract":[{"text":"In plants, clathrin mediated endocytosis (CME) represents the major route for cargo internalisation from the cell surface. It has been assumed to operate in an evolutionary conserved manner as in yeast and animals. Here we report characterisation of ultrastructure, dynamics and mechanisms of plant CME as allowed by our advancement in electron microscopy and quantitative live imaging techniques. Arabidopsis CME appears to follow the constant curvature model and the bona fide CME population generates vesicles of a predominantly hexagonal-basket type; larger and with faster kinetics than in other models. Contrary to the existing paradigm, actin is dispensable for CME events at the plasma membrane but plays a unique role in collecting endocytic vesicles, sorting of internalised cargos and directional endosome movement that itself actively promote CME events. Internalized vesicles display a strongly delayed and sequential uncoating. These unique features highlight the independent evolution of the plant CME mechanism during the autonomous rise of multicellularity in eukaryotes.","lang":"eng"}],"date_created":"2020-02-16T23:00:50Z","oa":1,"acknowledged_ssus":[{"_id":"LifeSc"},{"_id":"Bio"},{"_id":"EM-Fac"}],"file":[{"file_name":"2020_eLife_Narasimhan.pdf","content_type":"application/pdf","date_created":"2020-02-18T07:21:16Z","file_id":"7494","checksum":"2052daa4be5019534f3a42f200a09f32","file_size":7247468,"access_level":"open_access","creator":"dernst","date_updated":"2020-07-14T12:47:59Z","relation":"main_file"}],"type":"journal_article","quality_controlled":"1","status":"public","external_id":{"pmid":["31971511"],"isi":["000514104100001"]},"department":[{"_id":"JiFr"},{"_id":"GaTk"},{"_id":"EM-Fac"},{"_id":"SyCr"}],"pmid":1,"citation":{"mla":"Narasimhan, Madhumitha, et al. “Evolutionarily Unique Mechanistic Framework of Clathrin-Mediated Endocytosis in Plants.” <i>ELife</i>, vol. 9, e52067, eLife Sciences Publications, 2020, doi:<a href=\"https://doi.org/10.7554/eLife.52067\">10.7554/eLife.52067</a>.","ama":"Narasimhan M, Johnson AJ, Prizak R, et al. Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants. <i>eLife</i>. 2020;9. doi:<a href=\"https://doi.org/10.7554/eLife.52067\">10.7554/eLife.52067</a>","ista":"Narasimhan M, Johnson AJ, Prizak R, Kaufmann W, Tan S, Casillas Perez BE, Friml J. 2020. Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants. eLife. 9, e52067.","short":"M. Narasimhan, A.J. Johnson, R. Prizak, W. Kaufmann, S. Tan, B.E. Casillas Perez, J. Friml, ELife 9 (2020).","apa":"Narasimhan, M., Johnson, A. J., Prizak, R., Kaufmann, W., Tan, S., Casillas Perez, B. E., &#38; Friml, J. (2020). Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.52067\">https://doi.org/10.7554/eLife.52067</a>","chicago":"Narasimhan, Madhumitha, Alexander J Johnson, Roshan Prizak, Walter Kaufmann, Shutang Tan, Barbara E Casillas Perez, and Jiří Friml. “Evolutionarily Unique Mechanistic Framework of Clathrin-Mediated Endocytosis in Plants.” <i>ELife</i>. eLife Sciences Publications, 2020. <a href=\"https://doi.org/10.7554/eLife.52067\">https://doi.org/10.7554/eLife.52067</a>.","ieee":"M. Narasimhan <i>et al.</i>, “Evolutionarily unique mechanistic framework of clathrin-mediated endocytosis in plants,” <i>eLife</i>, vol. 9. eLife Sciences Publications, 2020."},"publication_identifier":{"eissn":["2050-084X"]},"has_accepted_license":"1","language":[{"iso":"eng"}],"article_processing_charge":"No","date_updated":"2025-04-14T07:45:03Z","_id":"7490","publication":"eLife","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","file_date_updated":"2020-07-14T12:47:59Z","intvolume":"         9","isi":1,"tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"publisher":"eLife Sciences Publications","publication_status":"published","oa_version":"Published Version","ec_funded":1,"date_published":"2020-01-23T00:00:00Z","volume":9},{"article_processing_charge":"No","date_updated":"2026-04-02T14:28:17Z","_id":"7878","external_id":{"isi":["000535191600001"],"pmid":["32401196"]},"pmid":1,"department":[{"_id":"RySh"}],"publication_identifier":{"eissn":["2050-084X"]},"citation":{"apa":"Bao, J., Graupner, M., Astorga, G., Collin, T., Jalil, A., Indriati, D. W., … Llano, I. (2020). Synergism of type 1 metabotropic and ionotropic glutamate receptors in cerebellar molecular layer interneurons in vivo. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.56839\">https://doi.org/10.7554/eLife.56839</a>","ama":"Bao J, Graupner M, Astorga G, et al. Synergism of type 1 metabotropic and ionotropic glutamate receptors in cerebellar molecular layer interneurons in vivo. <i>eLife</i>. 2020;9. doi:<a href=\"https://doi.org/10.7554/eLife.56839\">10.7554/eLife.56839</a>","mla":"Bao, Jin, et al. “Synergism of Type 1 Metabotropic and Ionotropic Glutamate Receptors in Cerebellar Molecular Layer Interneurons in Vivo.” <i>ELife</i>, vol. 9, e56839, eLife Sciences Publications, 2020, doi:<a href=\"https://doi.org/10.7554/eLife.56839\">10.7554/eLife.56839</a>.","ista":"Bao J, Graupner M, Astorga G, Collin T, Jalil A, Indriati DW, Bradley J, Shigemoto R, Llano I. 2020. Synergism of type 1 metabotropic and ionotropic glutamate receptors in cerebellar molecular layer interneurons in vivo. eLife. 9, e56839.","short":"J. Bao, M. Graupner, G. Astorga, T. Collin, A. Jalil, D.W. Indriati, J. Bradley, R. Shigemoto, I. Llano, ELife 9 (2020).","chicago":"Bao, Jin, Michael Graupner, Guadalupe Astorga, Thibault Collin, Abdelali Jalil, Dwi Wahyu Indriati, Jonathan Bradley, Ryuichi Shigemoto, and Isabel Llano. “Synergism of Type 1 Metabotropic and Ionotropic Glutamate Receptors in Cerebellar Molecular Layer Interneurons in Vivo.” <i>ELife</i>. eLife Sciences Publications, 2020. <a href=\"https://doi.org/10.7554/eLife.56839\">https://doi.org/10.7554/eLife.56839</a>.","ieee":"J. Bao <i>et al.</i>, “Synergism of type 1 metabotropic and ionotropic glutamate receptors in cerebellar molecular layer interneurons in vivo,” <i>eLife</i>, vol. 9. eLife Sciences Publications, 2020."},"has_accepted_license":"1","language":[{"iso":"eng"}],"publisher":"eLife Sciences Publications","publication_status":"published","oa_version":"Published Version","date_published":"2020-05-13T00:00:00Z","volume":9,"publication":"eLife","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","intvolume":"         9","file_date_updated":"2020-07-14T12:48:04Z","isi":1,"tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"ddc":["570"],"month":"05","title":"Synergism of type 1 metabotropic and ionotropic glutamate receptors in cerebellar molecular layer interneurons in vivo","doi":"10.7554/eLife.56839","year":"2020","author":[{"full_name":"Bao, Jin","first_name":"Jin","last_name":"Bao"},{"last_name":"Graupner","first_name":"Michael","full_name":"Graupner, Michael"},{"last_name":"Astorga","first_name":"Guadalupe","full_name":"Astorga, Guadalupe"},{"first_name":"Thibault","last_name":"Collin","full_name":"Collin, Thibault"},{"first_name":"Abdelali","last_name":"Jalil","full_name":"Jalil, Abdelali"},{"last_name":"Indriati","first_name":"Dwi Wahyu","full_name":"Indriati, Dwi Wahyu"},{"full_name":"Bradley, Jonathan","last_name":"Bradley","first_name":"Jonathan"},{"full_name":"Shigemoto, Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","last_name":"Shigemoto","first_name":"Ryuichi"},{"full_name":"Llano, Isabel","first_name":"Isabel","last_name":"Llano"}],"scopus_import":"1","day":"13","article_number":"e56839","article_type":"original","quality_controlled":"1","status":"public","abstract":[{"text":"Type 1 metabotropic glutamate receptors (mGluR1s) are key elements in neuronal signaling. While their function is well documented in slices, requirements for their activation in vivo are poorly understood. We examine this question in adult mice in vivo using 2-photon imaging of cerebellar molecular layer interneurons (MLIs) expressing GCaMP. In anesthetized mice, parallel fiber activation evokes beam-like Cai rises in postsynaptic MLIs which depend on co-activation of mGluR1s and ionotropic glutamate receptors (iGluRs). In awake mice, blocking mGluR1 decreases Cai rises associated with locomotion. In vitro studies and freeze-fracture electron microscopy show that the iGluR-mGluR1 interaction is synergistic and favored by close association of the two classes of receptors. Altogether our results suggest that mGluR1s, acting in synergy with iGluRs, potently contribute to processing cerebellar neuronal signaling under physiological conditions.","lang":"eng"}],"date_created":"2020-05-24T22:00:58Z","oa":1,"file":[{"relation":"main_file","date_updated":"2020-07-14T12:48:04Z","access_level":"open_access","creator":"dernst","file_size":4832050,"checksum":"8ea99bb6660cc407dbdb00c173b01683","file_id":"7891","date_created":"2020-05-26T09:34:54Z","content_type":"application/pdf","file_name":"2020_eLife_Bao.pdf"}],"type":"journal_article"},{"date_published":"2020-05-11T00:00:00Z","volume":9,"oa_version":"Published Version","ec_funded":1,"publisher":"eLife Sciences Publications","publication_status":"published","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"isi":1,"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","file_date_updated":"2020-07-14T12:48:05Z","intvolume":"         9","publication":"eLife","_id":"7909","article_processing_charge":"No","date_updated":"2026-04-02T14:32:12Z","has_accepted_license":"1","language":[{"iso":"eng"}],"pmid":1,"department":[{"_id":"MiSi"}],"citation":{"apa":"Damiano-Guercio, J., Kurzawa, L., Müller, J., Dimchev, G. A., Schaks, M., Nemethova, M., … Faix, J. (2020). Loss of Ena/VASP interferes with lamellipodium architecture, motility and integrin-dependent adhesion. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.55351\">https://doi.org/10.7554/eLife.55351</a>","mla":"Damiano-Guercio, Julia, et al. “Loss of Ena/VASP Interferes with Lamellipodium Architecture, Motility and Integrin-Dependent Adhesion.” <i>ELife</i>, vol. 9, e55351, eLife Sciences Publications, 2020, doi:<a href=\"https://doi.org/10.7554/eLife.55351\">10.7554/eLife.55351</a>.","ama":"Damiano-Guercio J, Kurzawa L, Müller J, et al. Loss of Ena/VASP interferes with lamellipodium architecture, motility and integrin-dependent adhesion. <i>eLife</i>. 2020;9. doi:<a href=\"https://doi.org/10.7554/eLife.55351\">10.7554/eLife.55351</a>","ista":"Damiano-Guercio J, Kurzawa L, Müller J, Dimchev GA, Schaks M, Nemethova M, Pokrant T, Brühmann S, Linkner J, Blanchoin L, Sixt MK, Rottner K, Faix J. 2020. Loss of Ena/VASP interferes with lamellipodium architecture, motility and integrin-dependent adhesion. eLife. 9, e55351.","short":"J. Damiano-Guercio, L. Kurzawa, J. Müller, G.A. Dimchev, M. Schaks, M. Nemethova, T. Pokrant, S. Brühmann, J. Linkner, L. Blanchoin, M.K. Sixt, K. Rottner, J. Faix, ELife 9 (2020).","chicago":"Damiano-Guercio, Julia, Laëtitia Kurzawa, Jan Müller, Georgi A Dimchev, Matthias Schaks, Maria Nemethova, Thomas Pokrant, et al. “Loss of Ena/VASP Interferes with Lamellipodium Architecture, Motility and Integrin-Dependent Adhesion.” <i>ELife</i>. eLife Sciences Publications, 2020. <a href=\"https://doi.org/10.7554/eLife.55351\">https://doi.org/10.7554/eLife.55351</a>.","ieee":"J. Damiano-Guercio <i>et al.</i>, “Loss of Ena/VASP interferes with lamellipodium architecture, motility and integrin-dependent adhesion,” <i>eLife</i>, vol. 9. eLife Sciences Publications, 2020."},"publication_identifier":{"eissn":["2050-084X"]},"external_id":{"isi":["000537208000001"],"pmid":["32391788"]},"status":"public","quality_controlled":"1","type":"journal_article","file":[{"relation":"main_file","date_updated":"2020-07-14T12:48:05Z","access_level":"open_access","creator":"dernst","file_size":10535713,"checksum":"d33bd4441b9a0195718ce1ba5d2c48a6","file_id":"7914","content_type":"application/pdf","date_created":"2020-06-02T10:35:37Z","file_name":"2020_eLife_Damiano_Guercio.pdf"}],"oa":1,"date_created":"2020-05-31T22:00:49Z","abstract":[{"text":"Cell migration entails networks and bundles of actin filaments termed lamellipodia and microspikes or filopodia, respectively, as well as focal adhesions, all of which recruit Ena/VASP family members hitherto thought to antagonize efficient cell motility. However, we find these proteins to act as positive regulators of migration in different murine cell lines. CRISPR/Cas9-mediated loss of Ena/VASP proteins reduced lamellipodial actin assembly and perturbed lamellipodial architecture, as evidenced by changed network geometry as well as reduction of filament length and number that was accompanied by abnormal Arp2/3 complex and heterodimeric capping protein accumulation. Loss of Ena/VASP function also abolished the formation of microspikes normally embedded in lamellipodia, but not of filopodia capable of emanating without lamellipodia. Ena/VASP-deficiency also impaired integrin-mediated adhesion accompanied by reduced traction forces exerted through these structures. Our data thus uncover novel Ena/VASP functions of these actin polymerases that are fully consistent with their promotion of cell migration.","lang":"eng"}],"title":"Loss of Ena/VASP interferes with lamellipodium architecture, motility and integrin-dependent adhesion","month":"05","ddc":["570"],"article_type":"original","article_number":"e55351","scopus_import":"1","day":"11","doi":"10.7554/eLife.55351","year":"2020","author":[{"full_name":"Damiano-Guercio, Julia","last_name":"Damiano-Guercio","first_name":"Julia"},{"full_name":"Kurzawa, Laëtitia","last_name":"Kurzawa","first_name":"Laëtitia"},{"id":"AD07FDB4-0F61-11EA-8158-C4CC64CEAA8D","full_name":"Müller, Jan","last_name":"Müller","first_name":"Jan"},{"full_name":"Dimchev, Georgi A","id":"38C393BE-F248-11E8-B48F-1D18A9856A87","last_name":"Dimchev","first_name":"Georgi A","orcid":"0000-0001-8370-6161"},{"full_name":"Schaks, Matthias","first_name":"Matthias","last_name":"Schaks"},{"first_name":"Maria","last_name":"Nemethova","id":"34E27F1C-F248-11E8-B48F-1D18A9856A87","full_name":"Nemethova, Maria"},{"first_name":"Thomas","last_name":"Pokrant","full_name":"Pokrant, Thomas"},{"full_name":"Brühmann, Stefan","last_name":"Brühmann","first_name":"Stefan"},{"full_name":"Linkner, Joern","first_name":"Joern","last_name":"Linkner"},{"first_name":"Laurent","last_name":"Blanchoin","full_name":"Blanchoin, Laurent"},{"full_name":"Sixt, Michael K","id":"41E9FBEA-F248-11E8-B48F-1D18A9856A87","first_name":"Michael K","last_name":"Sixt","orcid":"0000-0002-6620-9179"},{"last_name":"Rottner","first_name":"Klemens","full_name":"Rottner, Klemens"},{"last_name":"Faix","first_name":"Jan","full_name":"Faix, Jan"}],"project":[{"grant_number":"724373","call_identifier":"H2020","_id":"25FE9508-B435-11E9-9278-68D0E5697425","name":"Cellular Navigation Along Spatial Gradients"}]},{"file_date_updated":"2020-07-14T12:47:59Z","intvolume":"         9","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","publication":"eLife","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"isi":1,"publication_status":"published","publisher":"eLife Sciences Publications","volume":9,"date_published":"2020-01-20T00:00:00Z","oa_version":"Published Version","publication_identifier":{"eissn":["2050-084X"]},"citation":{"ama":"Kierdorf K, Hersperger F, Sharrock J, et al. Muscle function and homeostasis require cytokine inhibition of AKT activity in Drosophila. <i>eLife</i>. 2020;9. doi:<a href=\"https://doi.org/10.7554/eLife.51595\">10.7554/eLife.51595</a>","mla":"Kierdorf, Katrin, et al. “Muscle Function and Homeostasis Require Cytokine Inhibition of AKT Activity in Drosophila.” <i>ELife</i>, vol. 9, e51595, eLife Sciences Publications, 2020, doi:<a href=\"https://doi.org/10.7554/eLife.51595\">10.7554/eLife.51595</a>.","short":"K. Kierdorf, F. Hersperger, J. Sharrock, C.M. Vincent, P. Ustaoglu, J. Dou, A. György, O. Groß, D.E. Siekhaus, M.S. Dionne, ELife 9 (2020).","ista":"Kierdorf K, Hersperger F, Sharrock J, Vincent CM, Ustaoglu P, Dou J, György A, Groß O, Siekhaus DE, Dionne MS. 2020. Muscle function and homeostasis require cytokine inhibition of AKT activity in Drosophila. eLife. 9, e51595.","apa":"Kierdorf, K., Hersperger, F., Sharrock, J., Vincent, C. M., Ustaoglu, P., Dou, J., … Dionne, M. S. (2020). Muscle function and homeostasis require cytokine inhibition of AKT activity in Drosophila. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.51595\">https://doi.org/10.7554/eLife.51595</a>","chicago":"Kierdorf, Katrin, Fabian Hersperger, Jessica Sharrock, Crystal M. Vincent, Pinar Ustaoglu, Jiawen Dou, Attila György, Olaf Groß, Daria E Siekhaus, and Marc S. Dionne. “Muscle Function and Homeostasis Require Cytokine Inhibition of AKT Activity in Drosophila.” <i>ELife</i>. eLife Sciences Publications, 2020. <a href=\"https://doi.org/10.7554/eLife.51595\">https://doi.org/10.7554/eLife.51595</a>.","ieee":"K. Kierdorf <i>et al.</i>, “Muscle function and homeostasis require cytokine inhibition of AKT activity in Drosophila,” <i>eLife</i>, vol. 9. eLife Sciences Publications, 2020."},"department":[{"_id":"DaSi"}],"external_id":{"isi":["000512304800001"]},"language":[{"iso":"eng"}],"has_accepted_license":"1","_id":"7466","date_updated":"2026-04-03T09:24:34Z","article_processing_charge":"No","date_created":"2020-02-09T23:00:51Z","abstract":[{"lang":"eng","text":"Unpaired ligands are secreted signals that act via a GP130-like receptor, domeless, to activate JAK/STAT signalling in Drosophila. Like many mammalian cytokines, unpaireds can be activated by infection and other stresses and can promote insulin resistance in target tissues. However, the importance of this effect in non-inflammatory physiology is unknown. Here, we identify a requirement for unpaired-JAK signalling as a metabolic regulator in healthy adult Drosophila muscle. Adult muscles show basal JAK-STAT signalling activity in the absence of any immune challenge. Plasmatocytes (Drosophila macrophages) are an important source of this tonic signal. Loss of the dome receptor on adult muscles significantly reduces lifespan and causes local and systemic metabolic pathology. These pathologies result from hyperactivation of AKT and consequent deregulation of metabolism. Thus, we identify a cytokine signal that must be received in muscle to control AKT activity and metabolic homeostasis."}],"type":"journal_article","file":[{"access_level":"open_access","creator":"dernst","date_updated":"2020-07-14T12:47:59Z","relation":"main_file","file_id":"7470","checksum":"3a072be843f416c7a7d532a51dc0addb","file_size":4959933,"file_name":"2020_eLife_Kierdorf.pdf","date_created":"2020-02-10T08:53:16Z","content_type":"application/pdf"}],"oa":1,"status":"public","quality_controlled":"1","day":"20","scopus_import":"1","project":[{"call_identifier":"FWF","grant_number":"P29638","_id":"253B6E48-B435-11E9-9278-68D0E5697425","name":"The role of Drosophila TNF alpha in immune cell invasion"}],"author":[{"last_name":"Kierdorf","first_name":"Katrin","full_name":"Kierdorf, Katrin"},{"full_name":"Hersperger, Fabian","first_name":"Fabian","last_name":"Hersperger"},{"full_name":"Sharrock, Jessica","last_name":"Sharrock","first_name":"Jessica"},{"full_name":"Vincent, Crystal M.","first_name":"Crystal M.","last_name":"Vincent"},{"last_name":"Ustaoglu","first_name":"Pinar","full_name":"Ustaoglu, Pinar"},{"first_name":"Jiawen","last_name":"Dou","full_name":"Dou, Jiawen"},{"id":"3BCEDBE0-F248-11E8-B48F-1D18A9856A87","full_name":"György, Attila","orcid":"0000-0002-1819-198X","first_name":"Attila","last_name":"György"},{"full_name":"Groß, Olaf","first_name":"Olaf","last_name":"Groß"},{"orcid":"0000-0001-8323-8353","last_name":"Siekhaus","first_name":"Daria E","id":"3D224B9E-F248-11E8-B48F-1D18A9856A87","full_name":"Siekhaus, Daria E"},{"first_name":"Marc S.","last_name":"Dionne","full_name":"Dionne, Marc S."}],"doi":"10.7554/eLife.51595","year":"2020","article_type":"original","article_number":"e51595","ddc":["570"],"title":"Muscle function and homeostasis require cytokine inhibition of AKT activity in Drosophila","month":"01"},{"oa":1,"file":[{"success":1,"file_name":"2020_eLife_Gridchyn.pdf","date_created":"2020-11-09T09:17:40Z","content_type":"application/pdf","creator":"dernst","access_level":"open_access","date_updated":"2020-11-09T09:17:40Z","relation":"main_file","file_id":"8749","checksum":"6a7b0543c440f4c000a1864e69377d95","file_size":447669}],"type":"journal_article","abstract":[{"lang":"eng","text":"In vitro work revealed that excitatory synaptic inputs to hippocampal inhibitory interneurons could undergo Hebbian, associative, or non-associative plasticity. Both behavioral and learning-dependent reorganization of these connections has also been demonstrated by measuring spike transmission probabilities in pyramidal cell-interneuron spike cross-correlations that indicate monosynaptic connections. Here we investigated the activity-dependent modification of these connections during exploratory behavior in rats by optogenetically inhibiting pyramidal cell and interneuron subpopulations. Light application and associated firing alteration of pyramidal and interneuron populations led to lasting changes in pyramidal-interneuron connection weights as indicated by spike transmission changes. Spike transmission alterations were predicted by the light-mediated changes in the number of pre- and postsynaptic spike pairing events and by firing rate changes of interneurons but not pyramidal cells. This work demonstrates the presence of activity-dependent associative and non-associative reorganization of pyramidal-interneuron connections triggered by the optogenetic modification of the firing rate and spike synchrony of cells."}],"date_created":"2020-11-08T23:01:25Z","quality_controlled":"1","status":"public","corr_author":"1","article_number":"61106","article_type":"original","project":[{"name":"Interneuron plasticity during spatial learning","grant_number":"I2072-B27","call_identifier":"FWF","_id":"257D4372-B435-11E9-9278-68D0E5697425"},{"_id":"2654F984-B435-11E9-9278-68D0E5697425","grant_number":"I 3713-B27","call_identifier":"FWF","name":"Interneuro plasticity during spatial learning"}],"author":[{"orcid":"0000-0002-1807-1929","last_name":"Gridchyn","first_name":"Igor","full_name":"Gridchyn, Igor","id":"4B60654C-F248-11E8-B48F-1D18A9856A87"},{"id":"3B9D816C-F248-11E8-B48F-1D18A9856A87","full_name":"Schönenberger, Philipp","last_name":"Schönenberger","first_name":"Philipp"},{"id":"426376DC-F248-11E8-B48F-1D18A9856A87","full_name":"O'Neill, Joseph","last_name":"O'Neill","first_name":"Joseph"},{"id":"3FA14672-F248-11E8-B48F-1D18A9856A87","full_name":"Csicsvari, Jozsef L","orcid":"0000-0002-5193-4036","first_name":"Jozsef L","last_name":"Csicsvari"}],"year":"2020","doi":"10.7554/eLife.61106","day":"05","scopus_import":"1","month":"10","title":"Optogenetic inhibition-mediated activity-dependent modification of CA1 pyramidal-interneuron connections during behavior","ddc":["570"],"related_material":{"record":[{"id":"8563","relation":"research_data","status":"public"}]},"acknowledgement":"We thank Michele Nardin and Federico Stella for comments on an earlier version of the manuscript. K Deisseroth for providing the pAAV-CaMKIIα::eNpHR3.0-YFP plasmid through Addgene. E Boyden for providing AAV2/1.CaMKII::ArchT.GFP.WPRE.SV40 plasmid through Penn Vector Core. This work was supported by the Austrian Science Fund (I02072 and I03713) and a Swiss National Science Foundation grant to PS. The authors declare no conflicts of interest.","isi":1,"tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"publication":"eLife","file_date_updated":"2020-11-09T09:17:40Z","intvolume":"         9","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","oa_version":"Published Version","volume":9,"date_published":"2020-10-05T00:00:00Z","publication_status":"published","publisher":"eLife Sciences Publications","language":[{"iso":"eng"}],"has_accepted_license":"1","external_id":{"pmid":["33016875"],"isi":["000584369000001"]},"citation":{"ieee":"I. Gridchyn, P. Schönenberger, J. O’Neill, and J. L. Csicsvari, “Optogenetic inhibition-mediated activity-dependent modification of CA1 pyramidal-interneuron connections during behavior,” <i>eLife</i>, vol. 9. eLife Sciences Publications, 2020.","chicago":"Gridchyn, Igor, Philipp Schönenberger, Joseph O’Neill, and Jozsef L Csicsvari. “Optogenetic Inhibition-Mediated Activity-Dependent Modification of CA1 Pyramidal-Interneuron Connections during Behavior.” <i>ELife</i>. eLife Sciences Publications, 2020. <a href=\"https://doi.org/10.7554/eLife.61106\">https://doi.org/10.7554/eLife.61106</a>.","ista":"Gridchyn I, Schönenberger P, O’Neill J, Csicsvari JL. 2020. Optogenetic inhibition-mediated activity-dependent modification of CA1 pyramidal-interneuron connections during behavior. eLife. 9, 61106.","short":"I. Gridchyn, P. Schönenberger, J. O’Neill, J.L. Csicsvari, ELife 9 (2020).","mla":"Gridchyn, Igor, et al. “Optogenetic Inhibition-Mediated Activity-Dependent Modification of CA1 Pyramidal-Interneuron Connections during Behavior.” <i>ELife</i>, vol. 9, 61106, eLife Sciences Publications, 2020, doi:<a href=\"https://doi.org/10.7554/eLife.61106\">10.7554/eLife.61106</a>.","ama":"Gridchyn I, Schönenberger P, O’Neill J, Csicsvari JL. Optogenetic inhibition-mediated activity-dependent modification of CA1 pyramidal-interneuron connections during behavior. <i>eLife</i>. 2020;9. doi:<a href=\"https://doi.org/10.7554/eLife.61106\">10.7554/eLife.61106</a>","apa":"Gridchyn, I., Schönenberger, P., O’Neill, J., &#38; Csicsvari, J. L. (2020). Optogenetic inhibition-mediated activity-dependent modification of CA1 pyramidal-interneuron connections during behavior. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.61106\">https://doi.org/10.7554/eLife.61106</a>"},"publication_identifier":{"eissn":["2050-084X"]},"department":[{"_id":"JoCs"}],"pmid":1,"date_updated":"2026-04-07T08:37:11Z","article_processing_charge":"No","_id":"8740"},{"status":"public","quality_controlled":"1","date_created":"2020-08-24T06:24:04Z","abstract":[{"text":"Multiple resistance and pH adaptation (Mrp) antiporters are multi-subunit Na+ (or K+)/H+ exchangers representing an ancestor of many essential redox-driven proton pumps, such as respiratory complex I. The mechanism of coupling between ion or electron transfer and proton translocation in this large protein family is unknown. Here, we present the structure of the Mrp complex from Anoxybacillus flavithermus solved by cryo-EM at 3.0 Å resolution. It is a dimer of seven-subunit protomers with 50 trans-membrane helices each. Surface charge distribution within each monomer is remarkably asymmetric, revealing probable proton and sodium translocation pathways. On the basis of the structure we propose a mechanism where the coupling between sodium and proton translocation is facilitated by a series of electrostatic interactions between a cation and key charged residues. This mechanism is likely to be applicable to the entire family of redox proton pumps, where electron transfer to substrates replaces cation movements.","lang":"eng"}],"type":"journal_article","oa":1,"acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"LifeSc"}],"file":[{"access_level":"open_access","creator":"cziletti","date_updated":"2020-08-24T13:31:53Z","relation":"main_file","file_id":"8289","checksum":"b3656d14d5ddbb9d26e3074eea2d0c15","file_size":7320493,"success":1,"file_name":"2020_eLife_Steiner.pdf","date_created":"2020-08-24T13:31:53Z","content_type":"application/pdf"}],"related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"8353"}],"link":[{"relation":"press_release","url":"https://ist.ac.at/en/news/mystery-of-giant-proton-pump-solved/","description":"News on IST Homepage"}]},"ddc":["570"],"title":"Structure and mechanism of the Mrp complex, an ancient cation/proton antiporter","month":"07","day":"31","scopus_import":"1","author":[{"orcid":"0000-0003-0493-3775","first_name":"Julia","last_name":"Steiner","id":"3BB67EB0-F248-11E8-B48F-1D18A9856A87","full_name":"Steiner, Julia"},{"last_name":"Sazanov","first_name":"Leonid A","orcid":"0000-0002-0977-7989","id":"338D39FE-F248-11E8-B48F-1D18A9856A87","full_name":"Sazanov, Leonid A"}],"project":[{"_id":"26169496-B435-11E9-9278-68D0E5697425","grant_number":"24741","name":"Revealing the functional mechanism of Mrp antiporter, an ancestor of complex I"}],"doi":"10.7554/eLife.59407","year":"2020","article_type":"original","article_number":"e59407","publication_status":"published","publisher":"eLife Sciences Publications","date_published":"2020-07-31T00:00:00Z","volume":9,"oa_version":"Published Version","intvolume":"         9","file_date_updated":"2020-08-24T13:31:53Z","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","publication":"eLife","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"acknowledgement":"This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Electron Microscopy Facility (EMF), the Life Science Facility (LSF) and the IST high-performance computing cluster. We thank Dr Victor-Valentin Hodirnau and Daniel Johann Gütl from IST Austria for assistance with collecting cryo-EM data. We thank Prof. Masahiro Ito (Graduate School of Life Sciences, Toyo University, Japan) for a kind provision of plasmid DNA encoding Mrp from A. flavithermus WK1. JS is a recipient of a DOC Fellowship of the Austrian Academy of Sciences at the Institute of Science and Technology, Austria.","isi":1,"_id":"8284","date_updated":"2026-04-08T07:23:36Z","article_processing_charge":"No","citation":{"chicago":"Steiner, Julia, and Leonid A Sazanov. “Structure and Mechanism of the Mrp Complex, an Ancient Cation/Proton Antiporter.” <i>ELife</i>. eLife Sciences Publications, 2020. <a href=\"https://doi.org/10.7554/eLife.59407\">https://doi.org/10.7554/eLife.59407</a>.","ieee":"J. Steiner and L. A. Sazanov, “Structure and mechanism of the Mrp complex, an ancient cation/proton antiporter,” <i>eLife</i>, vol. 9. eLife Sciences Publications, 2020.","ama":"Steiner J, Sazanov LA. Structure and mechanism of the Mrp complex, an ancient cation/proton antiporter. <i>eLife</i>. 2020;9. doi:<a href=\"https://doi.org/10.7554/eLife.59407\">10.7554/eLife.59407</a>","mla":"Steiner, Julia, and Leonid A. Sazanov. “Structure and Mechanism of the Mrp Complex, an Ancient Cation/Proton Antiporter.” <i>ELife</i>, vol. 9, e59407, eLife Sciences Publications, 2020, doi:<a href=\"https://doi.org/10.7554/eLife.59407\">10.7554/eLife.59407</a>.","ista":"Steiner J, Sazanov LA. 2020. Structure and mechanism of the Mrp complex, an ancient cation/proton antiporter. eLife. 9, e59407.","short":"J. Steiner, L.A. Sazanov, ELife 9 (2020).","apa":"Steiner, J., &#38; Sazanov, L. A. (2020). Structure and mechanism of the Mrp complex, an ancient cation/proton antiporter. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.59407\">https://doi.org/10.7554/eLife.59407</a>"},"publication_identifier":{"eissn":["2050-084X"]},"department":[{"_id":"LeSa"}],"pmid":1,"external_id":{"isi":["000562123600001"],"pmid":["32735215"]},"language":[{"iso":"eng"}],"has_accepted_license":"1"},{"publisher":"eLife Sciences Publications","publication_status":"published","volume":8,"date_published":"2019-03-21T00:00:00Z","oa_version":"Published Version","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","file_date_updated":"2020-07-14T12:47:24Z","intvolume":"         8","publication":"eLife","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"isi":1,"_id":"6230","article_processing_charge":"No","date_updated":"2026-04-02T14:03:15Z","department":[{"_id":"NiBa"}],"publication_identifier":{"eissn":["2050-084X"]},"citation":{"ieee":"N. H. Barton, J. Hermisson, and M. Nordborg, “Why structure matters,” <i>eLife</i>, vol. 8. eLife Sciences Publications, 2019.","chicago":"Barton, Nicholas H, Joachim Hermisson, and Magnus Nordborg. “Why Structure Matters.” <i>ELife</i>. eLife Sciences Publications, 2019. <a href=\"https://doi.org/10.7554/eLife.45380\">https://doi.org/10.7554/eLife.45380</a>.","ista":"Barton NH, Hermisson J, Nordborg M. 2019. Why structure matters. eLife. 8, e45380.","short":"N.H. Barton, J. Hermisson, M. Nordborg, ELife 8 (2019).","mla":"Barton, Nicholas H., et al. “Why Structure Matters.” <i>ELife</i>, vol. 8, e45380, eLife Sciences Publications, 2019, doi:<a href=\"https://doi.org/10.7554/eLife.45380\">10.7554/eLife.45380</a>.","ama":"Barton NH, Hermisson J, Nordborg M. Why structure matters. <i>eLife</i>. 2019;8. doi:<a href=\"https://doi.org/10.7554/eLife.45380\">10.7554/eLife.45380</a>","apa":"Barton, N. H., Hermisson, J., &#38; Nordborg, M. (2019). Why structure matters. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.45380\">https://doi.org/10.7554/eLife.45380</a>"},"external_id":{"isi":["000461988300001"]},"has_accepted_license":"1","language":[{"iso":"eng"}],"status":"public","quality_controlled":"1","date_created":"2019-04-07T21:59:15Z","abstract":[{"text":"Great care is needed when interpreting claims about the genetic basis of human variation based on data from genome-wide association studies.","lang":"eng"}],"type":"journal_article","oa":1,"file":[{"content_type":"application/pdf","date_created":"2019-04-11T11:43:38Z","file_name":"2019_eLife_Barton.pdf","file_size":298466,"checksum":"130d7544b57df4a6787e1263c2d7ea43","file_id":"6293","relation":"main_file","date_updated":"2020-07-14T12:47:24Z","creator":"dernst","access_level":"open_access"}],"related_material":{"link":[{"relation":"press_release","description":"News on IST Homepage","url":"https://ist.ac.at/en/news/body-height-bmi-disease-risk-co/"}]},"ddc":["570"],"title":"Why structure matters","month":"03","scopus_import":"1","day":"21","year":"2019","doi":"10.7554/eLife.45380","author":[{"full_name":"Barton, Nicholas H","id":"4880FE40-F248-11E8-B48F-1D18A9856A87","last_name":"Barton","first_name":"Nicholas H","orcid":"0000-0002-8548-5240"},{"full_name":"Hermisson, Joachim","last_name":"Hermisson","first_name":"Joachim"},{"full_name":"Nordborg, Magnus","last_name":"Nordborg","first_name":"Magnus"}],"article_number":"e45380"},{"date_updated":"2026-04-03T09:40:28Z","article_processing_charge":"No","_id":"6868","language":[{"iso":"eng"}],"has_accepted_license":"1","external_id":{"isi":["000485663900001"]},"publication_identifier":{"eissn":["2050-084X"]},"citation":{"ista":"Byczkowicz N, Eshra A, Montanaro-Punzengruber J-C, Trevisiol A, Hirrlinger J, Kole MH, Shigemoto R, Hallermann S. 2019. HCN channel-mediated neuromodulation can control action potential velocity and fidelity in central axons. eLife. 8, e42766.","short":"N. Byczkowicz, A. Eshra, J.-C. Montanaro-Punzengruber, A. Trevisiol, J. Hirrlinger, M.H. Kole, R. Shigemoto, S. Hallermann, ELife 8 (2019).","ama":"Byczkowicz N, Eshra A, Montanaro-Punzengruber J-C, et al. HCN channel-mediated neuromodulation can control action potential velocity and fidelity in central axons. <i>eLife</i>. 2019;8. doi:<a href=\"https://doi.org/10.7554/eLife.42766\">10.7554/eLife.42766</a>","mla":"Byczkowicz, Niklas, et al. “HCN Channel-Mediated Neuromodulation Can Control Action Potential Velocity and Fidelity in Central Axons.” <i>ELife</i>, vol. 8, e42766, eLife Sciences Publications, 2019, doi:<a href=\"https://doi.org/10.7554/eLife.42766\">10.7554/eLife.42766</a>.","apa":"Byczkowicz, N., Eshra, A., Montanaro-Punzengruber, J.-C., Trevisiol, A., Hirrlinger, J., Kole, M. H., … Hallermann, S. (2019). HCN channel-mediated neuromodulation can control action potential velocity and fidelity in central axons. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.42766\">https://doi.org/10.7554/eLife.42766</a>","ieee":"N. Byczkowicz <i>et al.</i>, “HCN channel-mediated neuromodulation can control action potential velocity and fidelity in central axons,” <i>eLife</i>, vol. 8. eLife Sciences Publications, 2019.","chicago":"Byczkowicz, Niklas, Abdelmoneim Eshra, Jacqueline-Claire Montanaro-Punzengruber, Andrea Trevisiol, Johannes Hirrlinger, Maarten Hp Kole, Ryuichi Shigemoto, and Stefan Hallermann. “HCN Channel-Mediated Neuromodulation Can Control Action Potential Velocity and Fidelity in Central Axons.” <i>ELife</i>. eLife Sciences Publications, 2019. <a href=\"https://doi.org/10.7554/eLife.42766\">https://doi.org/10.7554/eLife.42766</a>."},"department":[{"_id":"RySh"}],"oa_version":"Published Version","date_published":"2019-09-09T00:00:00Z","volume":8,"publication_status":"published","publisher":"eLife Sciences Publications","isi":1,"tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"publication":"eLife","intvolume":"         8","file_date_updated":"2020-07-14T12:47:42Z","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","month":"09","title":"HCN channel-mediated neuromodulation can control action potential velocity and fidelity in central axons","ddc":["570"],"article_number":"e42766","article_type":"original","author":[{"first_name":"Niklas","last_name":"Byczkowicz","full_name":"Byczkowicz, Niklas"},{"full_name":"Eshra, Abdelmoneim","last_name":"Eshra","first_name":"Abdelmoneim"},{"id":"3786AB44-F248-11E8-B48F-1D18A9856A87","full_name":"Montanaro-Punzengruber, Jacqueline-Claire","first_name":"Jacqueline-Claire","last_name":"Montanaro-Punzengruber"},{"last_name":"Trevisiol","first_name":"Andrea","full_name":"Trevisiol, Andrea"},{"full_name":"Hirrlinger, Johannes","last_name":"Hirrlinger","first_name":"Johannes"},{"full_name":"Kole, Maarten Hp","last_name":"Kole","first_name":"Maarten Hp"},{"full_name":"Shigemoto, Ryuichi","id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","last_name":"Shigemoto","first_name":"Ryuichi"},{"last_name":"Hallermann","first_name":"Stefan","full_name":"Hallermann, Stefan"}],"doi":"10.7554/eLife.42766","year":"2019","day":"09","scopus_import":"1","quality_controlled":"1","status":"public","file":[{"file_name":"2019_eLife_Byczkowicz.pdf","content_type":"application/pdf","date_created":"2019-09-16T13:14:33Z","creator":"dernst","access_level":"open_access","date_updated":"2020-07-14T12:47:42Z","relation":"main_file","file_id":"6880","checksum":"c350b7861ef0fb537cae8a3232aec016","file_size":4008137}],"oa":1,"type":"journal_article","abstract":[{"lang":"eng","text":"Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels control electrical rhythmicity and excitability in the heart and brain, but the function of HCN channels at the subcellular level in axons remains poorly understood. Here, we show that the action potential conduction velocity in both myelinated and unmyelinated central axons can be bidirectionally modulated by a HCN channel blocker, cyclic adenosine monophosphate (cAMP), and neuromodulators. Recordings from mouse cerebellar mossy fiber boutons show that HCN channels ensure reliable high-frequency firing and are strongly modulated by cAMP (EC50 40 mM; estimated endogenous cAMP concentration 13 mM). In addition, immunogold-electron microscopy revealed HCN2 as the dominating subunit in cerebellar mossy fibers. Computational modeling indicated that HCN2 channels control conduction velocity primarily by altering the resting membrane potential\r\nand are associated with significant metabolic costs. These results suggest that the cAMP-HCN pathway provides neuromodulators with an opportunity to finely tune energy consumption and temporal delays across axons in the brain."}],"date_created":"2019-09-15T22:00:43Z"},{"tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"isi":1,"acknowledgement":"We thank the CIMR flow cytometry core facility team (Reiner Schulte, Chiara Cossetti and Gabriela Grondys-Kotarba) for assistance with FACS, the Huntington lab for access to the Octet machine, Steffen Preissler for advice on data interpretation, Roman Kityk and Nicole Luebbehusen for help and advice with HX-MS experiments.","user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","intvolume":"         8","file_date_updated":"2020-11-19T11:37:41Z","publication":"eLife","date_published":"2019-12-24T00:00:00Z","volume":8,"oa_version":"Published Version","publisher":"eLife Sciences Publications","publication_status":"published","has_accepted_license":"1","language":[{"iso":"eng"}],"pmid":1,"department":[{"_id":"MaDe"}],"citation":{"mla":"Amin-Wetzel, Niko Paresh, et al. “Unstructured Regions in IRE1α Specify BiP-Mediated Destabilisation of the Luminal Domain Dimer and Repression of the UPR.” <i>ELife</i>, vol. 8, e50793, eLife Sciences Publications, 2019, doi:<a href=\"https://doi.org/10.7554/eLife.50793\">10.7554/eLife.50793</a>.","ama":"Amin-Wetzel NP, Neidhardt L, Yan Y, Mayer MP, Ron D. Unstructured regions in IRE1α specify BiP-mediated destabilisation of the luminal domain dimer and repression of the UPR. <i>eLife</i>. 2019;8. doi:<a href=\"https://doi.org/10.7554/eLife.50793\">10.7554/eLife.50793</a>","ista":"Amin-Wetzel NP, Neidhardt L, Yan Y, Mayer MP, Ron D. 2019. Unstructured regions in IRE1α specify BiP-mediated destabilisation of the luminal domain dimer and repression of the UPR. eLife. 8, e50793.","short":"N.P. Amin-Wetzel, L. Neidhardt, Y. Yan, M.P. Mayer, D. Ron, ELife 8 (2019).","apa":"Amin-Wetzel, N. P., Neidhardt, L., Yan, Y., Mayer, M. P., &#38; Ron, D. (2019). Unstructured regions in IRE1α specify BiP-mediated destabilisation of the luminal domain dimer and repression of the UPR. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.50793\">https://doi.org/10.7554/eLife.50793</a>","chicago":"Amin-Wetzel, Niko Paresh, Lisa Neidhardt, Yahui Yan, Matthias P. Mayer, and David Ron. “Unstructured Regions in IRE1α Specify BiP-Mediated Destabilisation of the Luminal Domain Dimer and Repression of the UPR.” <i>ELife</i>. eLife Sciences Publications, 2019. <a href=\"https://doi.org/10.7554/eLife.50793\">https://doi.org/10.7554/eLife.50793</a>.","ieee":"N. P. Amin-Wetzel, L. Neidhardt, Y. Yan, M. P. Mayer, and D. Ron, “Unstructured regions in IRE1α specify BiP-mediated destabilisation of the luminal domain dimer and repression of the UPR,” <i>eLife</i>, vol. 8. eLife Sciences Publications, 2019."},"publication_identifier":{"eissn":["2050-084X"]},"external_id":{"isi":["000512303700001"],"pmid":["31873072"]},"_id":"7340","article_processing_charge":"No","date_updated":"2026-04-03T09:44:20Z","type":"journal_article","file":[{"file_name":"2019_eLife_AminWetzel.pdf","date_created":"2020-11-19T11:37:41Z","content_type":"application/pdf","success":1,"checksum":"29fcbcd8c1fc7f11a596ed7f14ea1c82","file_size":4817384,"file_id":"8777","relation":"main_file","creator":"dernst","access_level":"open_access","date_updated":"2020-11-19T11:37:41Z"}],"oa":1,"date_created":"2020-01-19T23:00:39Z","abstract":[{"lang":"eng","text":"Coupling of endoplasmic reticulum stress to dimerisation‑dependent activation of the UPR transducer IRE1 is incompletely understood. Whilst the luminal co-chaperone ERdj4 promotes a complex between the Hsp70 BiP and IRE1's stress-sensing luminal domain (IRE1LD) that favours the latter's monomeric inactive state and loss of ERdj4 de-represses IRE1, evidence linking these cellular and in vitro observations is presently lacking. We report that enforced loading of endogenous BiP onto endogenous IRE1α repressed UPR signalling in CHO cells and deletions in the IRE1α locus that de-repressed the UPR in cells, encode flexible regions of IRE1LD that mediated BiP‑induced monomerisation in vitro. Changes in the hydrogen exchange mass spectrometry profile of IRE1LD induced by ERdj4 and BiP confirmed monomerisation and were consistent with active destabilisation of the IRE1LD dimer. Together, these observations support a competition model whereby waning ER stress passively partitions ERdj4 and BiP to IRE1LD to initiate active repression of UPR signalling."}],"status":"public","quality_controlled":"1","article_type":"original","article_number":"e50793","scopus_import":"1","day":"24","doi":"10.7554/eLife.50793","year":"2019","author":[{"full_name":"Amin-Wetzel, Niko Paresh","id":"E95D3014-9D8C-11E9-9C80-D2F8E5697425","last_name":"Amin-Wetzel","first_name":"Niko Paresh"},{"full_name":"Neidhardt, Lisa","first_name":"Lisa","last_name":"Neidhardt"},{"full_name":"Yan, Yahui","first_name":"Yahui","last_name":"Yan"},{"full_name":"Mayer, Matthias P.","last_name":"Mayer","first_name":"Matthias P."},{"first_name":"David","last_name":"Ron","full_name":"Ron, David"}],"title":"Unstructured regions in IRE1α specify BiP-mediated destabilisation of the luminal domain dimer and repression of the UPR","month":"12","ddc":["570"]},{"publisher":"eLife Sciences Publications","publication_status":"published","date_published":"2019-11-18T00:00:00Z","volume":8,"oa_version":"Published Version","ec_funded":1,"user_id":"ba8df636-2132-11f1-aed0-ed93e2281fdd","intvolume":"         8","file_date_updated":"2020-07-14T12:47:53Z","publication":"eLife","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"isi":1,"_id":"7202","article_processing_charge":"No","date_updated":"2026-04-03T09:46:33Z","department":[{"_id":"SiHi"}],"pmid":1,"publication_identifier":{"eissn":["2050-084X"]},"citation":{"ama":"Llorca A, Ciceri G, Beattie RJ, et al. A stochastic framework of neurogenesis underlies the assembly of neocortical cytoarchitecture. <i>eLife</i>. 2019;8. doi:<a href=\"https://doi.org/10.7554/eLife.51381\">10.7554/eLife.51381</a>","mla":"Llorca, Alfredo, et al. “A Stochastic Framework of Neurogenesis Underlies the Assembly of Neocortical Cytoarchitecture.” <i>ELife</i>, vol. 8, e51381, eLife Sciences Publications, 2019, doi:<a href=\"https://doi.org/10.7554/eLife.51381\">10.7554/eLife.51381</a>.","short":"A. Llorca, G. Ciceri, R.J. Beattie, F.K. Wong, G. Diana, E. Serafeimidou-Pouliou, M. Fernández-Otero, C. Streicher, S.J. Arnold, M. Meyer, S. Hippenmeyer, M. Maravall, O. Marín, ELife 8 (2019).","ista":"Llorca A, Ciceri G, Beattie RJ, Wong FK, Diana G, Serafeimidou-Pouliou E, Fernández-Otero M, Streicher C, Arnold SJ, Meyer M, Hippenmeyer S, Maravall M, Marín O. 2019. A stochastic framework of neurogenesis underlies the assembly of neocortical cytoarchitecture. eLife. 8, e51381.","apa":"Llorca, A., Ciceri, G., Beattie, R. J., Wong, F. K., Diana, G., Serafeimidou-Pouliou, E., … Marín, O. (2019). A stochastic framework of neurogenesis underlies the assembly of neocortical cytoarchitecture. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/eLife.51381\">https://doi.org/10.7554/eLife.51381</a>","chicago":"Llorca, Alfredo, Gabriele Ciceri, Robert J Beattie, Fong Kuan Wong, Giovanni Diana, Eleni Serafeimidou-Pouliou, Marian Fernández-Otero, et al. “A Stochastic Framework of Neurogenesis Underlies the Assembly of Neocortical Cytoarchitecture.” <i>ELife</i>. eLife Sciences Publications, 2019. <a href=\"https://doi.org/10.7554/eLife.51381\">https://doi.org/10.7554/eLife.51381</a>.","ieee":"A. Llorca <i>et al.</i>, “A stochastic framework of neurogenesis underlies the assembly of neocortical cytoarchitecture,” <i>eLife</i>, vol. 8. eLife Sciences Publications, 2019."},"external_id":{"pmid":["31736464"],"isi":["000508156800001"]},"has_accepted_license":"1","language":[{"iso":"eng"}],"status":"public","quality_controlled":"1","date_created":"2019-12-22T23:00:42Z","abstract":[{"lang":"eng","text":"The cerebral cortex contains multiple areas with distinctive cytoarchitectonical patterns, but the cellular mechanisms underlying the emergence of this diversity remain unclear. Here, we have investigated the neuronal output of individual progenitor cells in the developing mouse neocortex using a combination of methods that together circumvent the biases and limitations of individual approaches. Our experimental results indicate that progenitor cells generate pyramidal cell lineages with a wide range of sizes and laminar configurations. Mathematical modelling indicates that these outcomes are compatible with a stochastic model of cortical neurogenesis in which progenitor cells undergo a series of probabilistic decisions that lead to the specification of very heterogeneous progenies. Our findings support a mechanism for cortical neurogenesis whose flexibility would make it capable to generate the diverse cytoarchitectures that characterize distinct neocortical areas."}],"type":"journal_article","oa":1,"file":[{"relation":"main_file","date_updated":"2020-07-14T12:47:53Z","access_level":"open_access","creator":"dernst","file_size":2960543,"checksum":"b460ecc33e1a68265e7adea775021f3a","file_id":"7503","content_type":"application/pdf","date_created":"2020-02-18T15:19:26Z","file_name":"2019_eLife_Llorca.pdf"}],"ddc":["570"],"title":"A stochastic framework of neurogenesis underlies the assembly of neocortical cytoarchitecture","month":"11","scopus_import":"1","day":"18","doi":"10.7554/eLife.51381","year":"2019","project":[{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780","call_identifier":"H2020","_id":"260018B0-B435-11E9-9278-68D0E5697425"},{"grant_number":"M02416","call_identifier":"FWF","_id":"264E56E2-B435-11E9-9278-68D0E5697425","name":"Molecular Mechanisms Regulating Gliogenesis in the Neocortex"}],"author":[{"last_name":"Llorca","first_name":"Alfredo","full_name":"Llorca, Alfredo"},{"first_name":"Gabriele","last_name":"Ciceri","full_name":"Ciceri, Gabriele"},{"orcid":"0000-0002-8483-8753","first_name":"Robert J","last_name":"Beattie","full_name":"Beattie, Robert J","id":"2E26DF60-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Fong Kuan","last_name":"Wong","full_name":"Wong, Fong Kuan"},{"full_name":"Diana, Giovanni","first_name":"Giovanni","last_name":"Diana"},{"full_name":"Serafeimidou-Pouliou, Eleni","last_name":"Serafeimidou-Pouliou","first_name":"Eleni"},{"first_name":"Marian","last_name":"Fernández-Otero","full_name":"Fernández-Otero, Marian"},{"first_name":"Carmen","last_name":"Streicher","id":"36BCB99C-F248-11E8-B48F-1D18A9856A87","full_name":"Streicher, Carmen"},{"last_name":"Arnold","first_name":"Sebastian J.","full_name":"Arnold, Sebastian J."},{"last_name":"Meyer","first_name":"Martin","full_name":"Meyer, Martin"},{"full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2279-1061","first_name":"Simon","last_name":"Hippenmeyer"},{"full_name":"Maravall, Miguel","last_name":"Maravall","first_name":"Miguel"},{"full_name":"Marín, Oscar","last_name":"Marín","first_name":"Oscar"}],"article_type":"original","article_number":"e51381"},{"date_updated":"2021-12-14T07:54:36Z","article_processing_charge":"No","_id":"9445","language":[{"iso":"eng"}],"has_accepted_license":"1","extern":"1","external_id":{"pmid":["29140247"]},"publication_identifier":{"eissn":["2050-084X"]},"citation":{"ieee":"D. B. Lyons and D. Zilberman, “DDM1 and Lsh remodelers allow methylation of DNA wrapped in nucleosomes,” <i>eLife</i>, vol. 6. eLife Sciences Publications, 2017.","chicago":"Lyons, David B, and Daniel Zilberman. “DDM1 and Lsh Remodelers Allow Methylation of DNA Wrapped in Nucleosomes.” <i>ELife</i>. eLife Sciences Publications, 2017. <a href=\"https://doi.org/10.7554/elife.30674\">https://doi.org/10.7554/elife.30674</a>.","ista":"Lyons DB, Zilberman D. 2017. DDM1 and Lsh remodelers allow methylation of DNA wrapped in nucleosomes. eLife. 6, e30674.","short":"D.B. Lyons, D. Zilberman, ELife 6 (2017).","ama":"Lyons DB, Zilberman D. DDM1 and Lsh remodelers allow methylation of DNA wrapped in nucleosomes. <i>eLife</i>. 2017;6. doi:<a href=\"https://doi.org/10.7554/elife.30674\">10.7554/elife.30674</a>","mla":"Lyons, David B., and Daniel Zilberman. “DDM1 and Lsh Remodelers Allow Methylation of DNA Wrapped in Nucleosomes.” <i>ELife</i>, vol. 6, e30674, eLife Sciences Publications, 2017, doi:<a href=\"https://doi.org/10.7554/elife.30674\">10.7554/elife.30674</a>.","apa":"Lyons, D. B., &#38; Zilberman, D. (2017). DDM1 and Lsh remodelers allow methylation of DNA wrapped in nucleosomes. <i>ELife</i>. eLife Sciences Publications. <a href=\"https://doi.org/10.7554/elife.30674\">https://doi.org/10.7554/elife.30674</a>"},"pmid":1,"department":[{"_id":"DaZi"}],"oa_version":"Published Version","volume":6,"date_published":"2017-11-15T00:00:00Z","publication_status":"published","publisher":"eLife Sciences Publications","tmp":{"short":"CC BY (4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","image":"/images/cc_by.png"},"publication":"eLife","file_date_updated":"2021-06-02T14:33:36Z","intvolume":"         6","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","month":"11","title":"DDM1 and Lsh remodelers allow methylation of DNA wrapped in nucleosomes","ddc":["570"],"article_number":"e30674","article_type":"original","author":[{"last_name":"Lyons","first_name":"David B","full_name":"Lyons, David B"},{"orcid":"0000-0002-0123-8649","last_name":"Zilberman","first_name":"Daniel","id":"6973db13-dd5f-11ea-814e-b3e5455e9ed1","full_name":"Zilberman, Daniel"}],"doi":"10.7554/elife.30674","year":"2017","day":"15","scopus_import":"1","quality_controlled":"1","status":"public","oa":1,"file":[{"success":1,"content_type":"application/pdf","date_created":"2021-06-02T14:33:36Z","file_name":"2017_eLife_Lyons.pdf","date_updated":"2021-06-02T14:33:36Z","access_level":"open_access","creator":"cziletti","relation":"main_file","file_id":"9446","file_size":1603102,"checksum":"4cfcdd67511ae4aed3d993550e46e146"}],"type":"journal_article","abstract":[{"lang":"eng","text":"Cytosine methylation regulates essential genome functions across eukaryotes, but the fundamental question of whether nucleosomal or naked DNA is the preferred substrate of plant and animal methyltransferases remains unresolved. Here, we show that genetic inactivation of a single DDM1/Lsh family nucleosome remodeler biases methylation toward inter-nucleosomal linker DNA in Arabidopsis thaliana and mouse. We find that DDM1 enables methylation of DNA bound to the nucleosome, suggesting that nucleosome-free DNA is the preferred substrate of eukaryotic methyltransferases in vivo. Furthermore, we show that simultaneous mutation of DDM1 and linker histone H1 in Arabidopsis reproduces the strong linker-specific methylation patterns of species that diverged from flowering plants and animals over a billion years ago. Our results indicate that in the absence of remodeling, nucleosomes are strong barriers to DNA methyltransferases. Linker-specific methylation can evolve simply by breaking the connection between nucleosome remodeling and DNA methylation."}],"date_created":"2021-06-02T14:28:58Z"}]