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This work was supported by European Commission’s Seventh Framework Programme under grant agreement no. 279113 (OCTIPS; www.octips.eu).\r\nOpen Access funding enabled and organized by Projekt DEAL.","year":"2023","publisher":"Springer Nature","department":[{"_id":"JoDa"}],"publication_status":"published","related_material":{"record":[{"relation":"other","status":"public","id":"12115"}]},"author":[{"last_name":"Glajzer","first_name":"Jacek","full_name":"Glajzer, Jacek"},{"full_name":"Castillo-Tong, Dan Cacsire","first_name":"Dan Cacsire","last_name":"Castillo-Tong"},{"full_name":"Richter, Rolf","first_name":"Rolf","last_name":"Richter"},{"first_name":"Ignace","last_name":"Vergote","full_name":"Vergote, Ignace"},{"first_name":"Hagen","last_name":"Kulbe","full_name":"Kulbe, Hagen"},{"last_name":"Vanderstichele","first_name":"Adriaan","full_name":"Vanderstichele, Adriaan"},{"full_name":"Ruscito, Ilary","last_name":"Ruscito","first_name":"Ilary"},{"first_name":"Fabian","last_name":"Trillsch","full_name":"Trillsch, Fabian"},{"first_name":"Alexander","last_name":"Mustea","full_name":"Mustea, Alexander"},{"full_name":"Kreuzinger, Caroline","id":"382077BA-F248-11E8-B48F-1D18A9856A87","last_name":"Kreuzinger","first_name":"Caroline"},{"last_name":"Gourley","first_name":"Charlie","full_name":"Gourley, Charlie"},{"last_name":"Gabra","first_name":"Hani","full_name":"Gabra, Hani"},{"first_name":"Eliane T.","last_name":"Taube","full_name":"Taube, Eliane T."},{"full_name":"Dorigo, Oliver","last_name":"Dorigo","first_name":"Oliver"},{"full_name":"Horst, David","first_name":"David","last_name":"Horst"},{"first_name":"Carlotta","last_name":"Keunecke","full_name":"Keunecke, Carlotta"},{"last_name":"Baum","first_name":"Joanna","full_name":"Baum, Joanna"},{"last_name":"Angelotti","first_name":"Timothy","full_name":"Angelotti, Timothy"},{"full_name":"Sehouli, Jalid","last_name":"Sehouli","first_name":"Jalid"},{"full_name":"Braicu, Elena Ioana","first_name":"Elena Ioana","last_name":"Braicu"}],"volume":30,"date_updated":"2023-09-05T15:18:37Z","date_created":"2023-01-16T09:44:36Z","file_date_updated":"2023-02-02T13:01:20Z","citation":{"ista":"Glajzer J, Castillo-Tong DC, Richter R, Vergote I, Kulbe H, Vanderstichele A, Ruscito I, Trillsch F, Mustea A, Kreuzinger C, Gourley C, Gabra H, Taube ET, Dorigo O, Horst D, Keunecke C, Baum J, Angelotti T, Sehouli J, Braicu EI. 2023. Impact of BRCA mutation status on tumor dissemination pattern, surgical outcome and patient survival in primary and recurrent high-grade serous ovarian cancer: A multicenter retrospective study by the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) consortium. Annals of Surgical Oncology. 30, 35–45.","ieee":"J. Glajzer et al., “Impact of BRCA mutation status on tumor dissemination pattern, surgical outcome and patient survival in primary and recurrent high-grade serous ovarian cancer: A multicenter retrospective study by the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) consortium,” Annals of Surgical Oncology, vol. 30. Springer Nature, pp. 35–45, 2023.","apa":"Glajzer, J., Castillo-Tong, D. C., Richter, R., Vergote, I., Kulbe, H., Vanderstichele, A., … Braicu, E. I. (2023). Impact of BRCA mutation status on tumor dissemination pattern, surgical outcome and patient survival in primary and recurrent high-grade serous ovarian cancer: A multicenter retrospective study by the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) consortium. Annals of Surgical Oncology. Springer Nature. https://doi.org/10.1245/s10434-022-12459-3","ama":"Glajzer J, Castillo-Tong DC, Richter R, et al. Impact of BRCA mutation status on tumor dissemination pattern, surgical outcome and patient survival in primary and recurrent high-grade serous ovarian cancer: A multicenter retrospective study by the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) consortium. Annals of Surgical Oncology. 2023;30:35-45. doi:10.1245/s10434-022-12459-3","chicago":"Glajzer, Jacek, Dan Cacsire Castillo-Tong, Rolf Richter, Ignace Vergote, Hagen Kulbe, Adriaan Vanderstichele, Ilary Ruscito, et al. “Impact of BRCA Mutation Status on Tumor Dissemination Pattern, Surgical Outcome and Patient Survival in Primary and Recurrent High-Grade Serous Ovarian Cancer: A Multicenter Retrospective Study by the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) Consortium.” Annals of Surgical Oncology. Springer Nature, 2023. https://doi.org/10.1245/s10434-022-12459-3.","mla":"Glajzer, Jacek, et al. “Impact of BRCA Mutation Status on Tumor Dissemination Pattern, Surgical Outcome and Patient Survival in Primary and Recurrent High-Grade Serous Ovarian Cancer: A Multicenter Retrospective Study by the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) Consortium.” Annals of Surgical Oncology, vol. 30, Springer Nature, 2023, pp. 35–45, doi:10.1245/s10434-022-12459-3.","short":"J. Glajzer, D.C. Castillo-Tong, R. Richter, I. Vergote, H. Kulbe, A. Vanderstichele, I. Ruscito, F. Trillsch, A. Mustea, C. Kreuzinger, C. Gourley, H. Gabra, E.T. Taube, O. Dorigo, D. Horst, C. Keunecke, J. Baum, T. Angelotti, J. Sehouli, E.I. Braicu, Annals of Surgical Oncology 30 (2023) 35–45."},"publication":"Annals of Surgical Oncology","page":"35-45","article_type":"original","date_published":"2023-01-01T00:00:00Z","scopus_import":"1","keyword":["Oncology","Surgery"],"has_accepted_license":"1","article_processing_charge":"No","day":"01","_id":"12205","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","intvolume":" 30","status":"public","ddc":["610"],"title":"Impact of BRCA mutation status on tumor dissemination pattern, surgical outcome and patient survival in primary and recurrent high-grade serous ovarian cancer: A multicenter retrospective study by the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) consortium","oa_version":"Published Version","file":[{"content_type":"application/pdf","file_size":365865,"creator":"dernst","file_name":"2023_AnnalsSurgicalOncology_Glajzer.pdf","access_level":"open_access","date_updated":"2023-02-02T13:01:20Z","date_created":"2023-02-02T13:01:20Z","checksum":"36a1200e1011f4b2155a8041d0308f34","success":1,"relation":"main_file","file_id":"12490"}],"type":"journal_article","abstract":[{"text":"Background: This study seeks to evaluate the impact of breast cancer (BRCA) gene status on tumor dissemination pattern, surgical outcome and survival in a multicenter cohort of paired primary ovarian cancer (pOC) and recurrent ovarian cancer (rOC).\r\n\r\nPatients and Methods: Medical records and follow-up data from 190 patients were gathered retrospectively. All patients had surgery at pOC and at least one further rOC surgery at four European high-volume centers. Patients were divided into one cohort with confirmed mutation for BRCA1 and/or BRCA2 (BRCAmut) and a second cohort with BRCA wild type or unknown (BRCAwt). Patterns of tumor presentation, surgical outcome and survival data were analyzed between the two groups.\r\n\r\nResults: Patients with BRCAmut disease were on average 4 years younger and had significantly more tumor involvement upon diagnosis. Patients with BRCAmut disease showed higher debulking rates at all stages. Multivariate analysis showed that only patient age had significant predictive value for complete tumor resection in pOC. At rOC, however, only BRCAmut status significantly correlated with optimal debulking. Patients with BRCAmut disease showed significantly prolonged overall survival (OS) by 24.3 months. Progression-free survival (PFS) was prolonged in the BRCAmut group at all stages as well, reaching statistical significance during recurrence.\r\n\r\nConclusions: Patients with BRCAmut disease showed a more aggressive course of disease with earlier onset and more extensive tumor dissemination at pOC. However, surgical outcome and OS were significantly better in patients with BRCAmut disease compared with patients with BRCAwt disease. We therefore propose to consider BRCAmut status in regard to patient selection for cytoreductive surgery, especially in rOC.","lang":"eng"}]},{"_id":"12115","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","intvolume":" 30","title":"ASO Visual Abstract: Impact of BRCA mutation status on tumor dissemination pattern, surgical outcome, and patient survival in primary and recurrent high-grade serous ovarian cancer (HGSOC). A multicenter, retrospective study of the ovarian cancer therapy—innovative models prolong survival (OCTIPS) consortium","status":"public","oa_version":"Published Version","type":"journal_article","citation":{"chicago":"Glajzer, Jacek, Dan Cacsire Castillo-Tong, Rolf Richter, Ignace Vergote, Hagen Kulbe, Adriaan Vanderstichele, Ilary Ruscito, et al. “ASO Visual Abstract: Impact of BRCA Mutation Status on Tumor Dissemination Pattern, Surgical Outcome, and Patient Survival in Primary and Recurrent High-Grade Serous Ovarian Cancer (HGSOC). A Multicenter, Retrospective Study of the Ovarian Cancer Therapy—Innovative Models Prolong Survival (OCTIPS) Consortium.” Annals of Surgical Oncology. Springer Nature, 2023. https://doi.org/10.1245/s10434-022-12681-z.","short":"J. Glajzer, D.C. Castillo-Tong, R. Richter, I. Vergote, H. Kulbe, A. Vanderstichele, I. Ruscito, F. Trillsch, A. Mustea, C. Kreuzinger, C. Gourley, H. Gabra, E.T. Taube, O. Dorigo, D. Horst, C. Keunecke, J. Baum, T. 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C., Richter, R., Vergote, I., Kulbe, H., Vanderstichele, A., … Braicu, E. I. (2023). ASO Visual Abstract: Impact of BRCA mutation status on tumor dissemination pattern, surgical outcome, and patient survival in primary and recurrent high-grade serous ovarian cancer (HGSOC). A multicenter, retrospective study of the ovarian cancer therapy—innovative models prolong survival (OCTIPS) consortium. Annals of Surgical Oncology. Springer Nature. https://doi.org/10.1245/s10434-022-12681-z","ista":"Glajzer J, Castillo-Tong DC, Richter R, Vergote I, Kulbe H, Vanderstichele A, Ruscito I, Trillsch F, Mustea A, Kreuzinger C, Gourley C, Gabra H, Taube ET, Dorigo O, Horst D, Keunecke C, Baum J, Angelotti T, Sehouli J, Braicu EI. 2023. ASO Visual Abstract: Impact of BRCA mutation status on tumor dissemination pattern, surgical outcome, and patient survival in primary and recurrent high-grade serous ovarian cancer (HGSOC). 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Šuplata for hardware control support, and Márcia Cunha dos Santos for initial exploration of software. We thank Paul Henderson for advice on deep-learning training and Michael Sixt, Scott Boyd, and Tamara Weiss for discussions and critical reading of the manuscript. Luke Lavis (Janelia Research Campus) generously provided JF585-HaloTag ligand. ","year":"2023","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","license":"https://creativecommons.org/licenses/by-sa/4.0/","file_date_updated":"2023-05-18T19:51:52Z","abstract":[{"text":"3D-reconstruction of living brain tissue down to individual synapse level would create opportunities for decoding the dynamics and structure-function relationships of the brain’s complex and dense information processing network. However, it has been hindered by insufficient 3D-resolution, inadequate signal-to-noise-ratio, and prohibitive light burden in optical imaging, whereas electron microscopy is inherently static. Here we solved these challenges by developing an integrated optical/machine learning technology, LIONESS (Live Information-Optimized Nanoscopy Enabling Saturated Segmentation). It leverages optical modifications to stimulated emission depletion (STED) microscopy in comprehensively, extracellularly labelled tissue and prior information on sample structure via machine learning to simultaneously achieve isotropic super-resolution, high signal-to-noise-ratio, and compatibility with living tissue. This allows dense deep-learning-based instance segmentation and 3D-reconstruction at synapse level incorporating molecular, activity, and morphodynamic information. LIONESS opens up avenues for studying the dynamic functional (nano-)architecture of living brain tissue.","lang":"eng"}],"type":"research_data","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"doi":"10.15479/AT:ISTA:12817","date_published":"2023-05-19T00:00:00Z","tmp":{"short":"CC BY-SA (4.0)","image":"/images/cc_by_sa.png","name":"Creative Commons Attribution-ShareAlike 4.0 International Public License (CC BY-SA 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-sa/4.0/legalcode"},"citation":{"ieee":"J. G. Danzl, “Research data for the publication ‘Dense 4D nanoscale reconstruction of living brain tissue.’” Institute of Science and Technology Austria, 2023.","apa":"Danzl, J. G. (2023). Research data for the publication “Dense 4D nanoscale reconstruction of living brain tissue.” Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:12817","ista":"Danzl JG. 2023. Research data for the publication ‘Dense 4D nanoscale reconstruction of living brain tissue’, Institute of Science and Technology Austria, 10.15479/AT:ISTA:12817.","ama":"Danzl JG. Research data for the publication “Dense 4D nanoscale reconstruction of living brain tissue.” 2023. doi:10.15479/AT:ISTA:12817","chicago":"Danzl, Johann G. “Research Data for the Publication ‘Dense 4D Nanoscale Reconstruction of Living Brain Tissue.’” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/AT:ISTA:12817.","short":"J.G. Danzl, (2023).","mla":"Danzl, Johann G. Research Data for the Publication “Dense 4D Nanoscale Reconstruction of Living Brain Tissue.” Institute of Science and Technology Austria, 2023, doi:10.15479/AT:ISTA:12817."},"oa":1,"day":"19","month":"05","article_processing_charge":"No","has_accepted_license":"1"},{"abstract":[{"lang":"eng","text":"Three-dimensional (3D) reconstruction of living brain tissue down to an individual synapse level would create opportunities for decoding the dynamics and structure–function relationships of the brain’s complex and dense information processing network; however, this has been hindered by insufficient 3D resolution, inadequate signal-to-noise ratio and prohibitive light burden in optical imaging, whereas electron microscopy is inherently static. Here we solved these challenges by developing an integrated optical/machine-learning technology, LIONESS (live information-optimized nanoscopy enabling saturated segmentation). This leverages optical modifications to stimulated emission depletion microscopy in comprehensively, extracellularly labeled tissue and previous information on sample structure via machine learning to simultaneously achieve isotropic super-resolution, high signal-to-noise ratio and compatibility with living tissue. This allows dense deep-learning-based instance segmentation and 3D reconstruction at a synapse level, incorporating molecular, activity and morphodynamic information. LIONESS opens up avenues for studying the dynamic functional (nano-)architecture of living brain tissue."}],"type":"journal_article","oa_version":"Published Version","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"13267","status":"public","title":"Dense 4D nanoscale reconstruction of living brain tissue","intvolume":" 20","day":"01","article_processing_charge":"Yes","scopus_import":"1","date_published":"2023-08-01T00:00:00Z","publication":"Nature Methods","citation":{"ista":"Velicky P, Miguel Villalba E, Michalska JM, Lyudchik J, Wei D, Lin Z, Watson J, Troidl J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen J, Grant SGN, Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. 2023. Dense 4D nanoscale reconstruction of living brain tissue. Nature Methods. 20, 1256–1265.","apa":"Velicky, P., Miguel Villalba, E., Michalska, J. M., Lyudchik, J., Wei, D., Lin, Z., … Danzl, J. G. (2023). Dense 4D nanoscale reconstruction of living brain tissue. Nature Methods. Springer Nature. https://doi.org/10.1038/s41592-023-01936-6","ieee":"P. Velicky et al., “Dense 4D nanoscale reconstruction of living brain tissue,” Nature Methods, vol. 20. Springer Nature, pp. 1256–1265, 2023.","ama":"Velicky P, Miguel Villalba E, Michalska JM, et al. Dense 4D nanoscale reconstruction of living brain tissue. Nature Methods. 2023;20:1256-1265. doi:10.1038/s41592-023-01936-6","chicago":"Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Julia Lyudchik, Donglai Wei, Zudi Lin, Jake Watson, et al. “Dense 4D Nanoscale Reconstruction of Living Brain Tissue.” Nature Methods. Springer Nature, 2023. https://doi.org/10.1038/s41592-023-01936-6.","mla":"Velicky, Philipp, et al. “Dense 4D Nanoscale Reconstruction of Living Brain Tissue.” Nature Methods, vol. 20, Springer Nature, 2023, pp. 1256–65, doi:10.1038/s41592-023-01936-6.","short":"P. Velicky, E. Miguel Villalba, J.M. Michalska, J. Lyudchik, D. Wei, Z. Lin, J. Watson, J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri, J. Broichhagen, S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel, J.G. Danzl, Nature Methods 20 (2023) 1256–1265."},"article_type":"original","page":"1256-1265","ec_funded":1,"author":[{"full_name":"Velicky, Philipp","first_name":"Philipp","last_name":"Velicky","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2340-7431"},{"id":"3FB91342-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5665-0430","first_name":"Eder","last_name":"Miguel Villalba","full_name":"Miguel Villalba, Eder"},{"full_name":"Michalska, Julia M","last_name":"Michalska","first_name":"Julia M","orcid":"0000-0003-3862-1235","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Lyudchik, Julia","first_name":"Julia","last_name":"Lyudchik","id":"46E28B80-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Wei, Donglai","last_name":"Wei","first_name":"Donglai"},{"last_name":"Lin","first_name":"Zudi","full_name":"Lin, Zudi"},{"full_name":"Watson, Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E","orcid":"0000-0002-8698-3823","first_name":"Jake","last_name":"Watson"},{"last_name":"Troidl","first_name":"Jakob","full_name":"Troidl, Jakob"},{"first_name":"Johanna","last_name":"Beyer","full_name":"Beyer, Johanna"},{"full_name":"Ben Simon, Yoav","last_name":"Ben Simon","first_name":"Yoav","id":"43DF3136-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","last_name":"Sommer","first_name":"Christoph M","full_name":"Sommer, Christoph M"},{"full_name":"Jahr, Wiebke","last_name":"Jahr","first_name":"Wiebke","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87"},{"id":"9ac8f577-2357-11eb-997a-e566c5550886","last_name":"Cenameri","first_name":"Alban","full_name":"Cenameri, Alban"},{"last_name":"Broichhagen","first_name":"Johannes","full_name":"Broichhagen, Johannes"},{"last_name":"Grant","first_name":"Seth G.N.","full_name":"Grant, Seth G.N."},{"last_name":"Jonas","first_name":"Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M"},{"orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia","full_name":"Novarino, Gaia"},{"full_name":"Pfister, Hanspeter","last_name":"Pfister","first_name":"Hanspeter"},{"full_name":"Bickel, Bernd","orcid":"0000-0001-6511-9385","id":"49876194-F248-11E8-B48F-1D18A9856A87","last_name":"Bickel","first_name":"Bernd"},{"full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","last_name":"Danzl","first_name":"Johann G"}],"related_material":{"record":[{"id":"12817","status":"public","relation":"research_data"},{"status":"public","relation":"shorter_version","id":"14770"}],"link":[{"relation":"software","url":"https://github.com/danzllab/LIONESS"}]},"date_created":"2023-07-23T22:01:13Z","date_updated":"2024-01-10T08:37:48Z","volume":20,"acknowledgement":"We thank J. Vorlaufer, N. Agudelo and A. Wartak for microscope maintenance and troubleshooting, C. Kreuzinger and A. Freeman for technical assistance, M. Šuplata for hardware control support and M. Cunha dos Santos for initial exploration of software. We\r\nthank P. Henderson for advice on deep-learning training and M. Sixt, S. Boyd and T. Weiss for discussions and critical reading of the manuscript. L. Lavis (Janelia Research Campus) generously provided the JF585-HaloTag ligand. We acknowledge expert support by IST\r\nAustria’s scientific computing, imaging and optics, preclinical, library and laboratory support facilities and by the Miba machine shop. We gratefully acknowledge funding by the following sources: Austrian Science Fund (F.W.F.) grant no. I3600-B27 (J.G.D.), grant no. DK W1232\r\n(J.G.D. and J.M.M.) and grant no. Z 312-B27, Wittgenstein award (P.J.); the Gesellschaft für Forschungsförderung NÖ grant no. LSC18-022 (J.G.D.); an ISTA Interdisciplinary project grant (J.G.D. and B.B.); the European Union’s Horizon 2020 research and innovation programme,\r\nMarie-Skłodowska Curie grant 665385 (J.M.M. and J.L.); the European Union’s Horizon 2020 research and innovation programme, European Research Council grant no. 715767, MATERIALIZABLE (B.B.); grant no. 715508, REVERSEAUTISM (G.N.); grant no. 695568, SYNNOVATE (S.G.N.G.); and grant no. 692692, GIANTSYN (P.J.); the Simons\r\nFoundation Autism Research Initiative grant no. 529085 (S.G.N.G.); the Wellcome Trust Technology Development grant no. 202932 (S.G.N.G.); the Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.);\r\nthe Human Frontier Science Program postdoctoral fellowship LT000557/2018 (W.J.); and the National Science Foundation grant no. IIS-1835231 (H.P.) and NCS-FO-2124179 (H.P.).","year":"2023","pmid":1,"publication_status":"published","publisher":"Springer Nature","department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"},{"_id":"Bio"}],"month":"08","publication_identifier":{"issn":["1548-7091"],"eissn":["1548-7105"]},"doi":"10.1038/s41592-023-01936-6","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"E-Lib"},{"_id":"LifeSc"},{"_id":"M-Shop"}],"language":[{"iso":"eng"}],"main_file_link":[{"url":"https://doi.org/10.1038/s41592-023-01936-6","open_access":"1"}],"external_id":{"pmid":["37429995"],"isi":["001025621500001"]},"oa":1,"isi":1,"quality_controlled":"1","project":[{"grant_number":"I03600","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Optical control of synaptic function via adhesion molecules"},{"name":"Molecular Drug Targets","call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24"},{"name":"The Wittgenstein Prize","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312"},{"name":"High content imaging to decode human immune cell interactions in health and allergic disease","_id":"23889792-32DE-11EA-91FC-C7463DDC885E"},{"call_identifier":"H2020","name":"International IST Doctoral Program","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385"},{"grant_number":"715767","_id":"24F9549A-B435-11E9-9278-68D0E5697425","name":"MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and Modeling","call_identifier":"H2020"},{"_id":"25444568-B435-11E9-9278-68D0E5697425","grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020"},{"name":"Biophysics and circuit function of a giant cortical glumatergic synapse","call_identifier":"H2020","grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","name":"Synaptic computations of the hippocampal CA3 circuitry","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","grant_number":"101026635"},{"name":"High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration","grant_number":"LT00057","_id":"2668BFA0-B435-11E9-9278-68D0E5697425"}]},{"publication_identifier":{"issn":["1548-7091"],"eissn":["1548-7105"]},"month":"08","doi":"10.1038/s41592-023-01937-5","language":[{"iso":"eng"}],"external_id":{"isi":["001025621500002"]},"quality_controlled":"1","isi":1,"related_material":{"record":[{"id":"13267","status":"public","relation":"extended_version"}]},"author":[{"full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","first_name":"Johann G","last_name":"Danzl"},{"full_name":"Velicky, Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2340-7431","first_name":"Philipp","last_name":"Velicky"}],"volume":20,"date_updated":"2024-01-10T08:37:48Z","date_created":"2024-01-10T08:07:15Z","year":"2023","publisher":"Springer Nature","department":[{"_id":"JoDa"}],"publication_status":"published","article_processing_charge":"No","day":"01","scopus_import":"1","keyword":["Cell Biology","Molecular Biology","Biochemistry","Biotechnology"],"date_published":"2023-08-01T00:00:00Z","citation":{"ieee":"J. G. Danzl and P. Velicky, “LIONESS enables 4D nanoscale reconstruction of living brain tissue,” Nature Methods, vol. 20, no. 8. Springer Nature, pp. 1141–1142, 2023.","apa":"Danzl, J. G., & Velicky, P. (2023). LIONESS enables 4D nanoscale reconstruction of living brain tissue. Nature Methods. Springer Nature. https://doi.org/10.1038/s41592-023-01937-5","ista":"Danzl JG, Velicky P. 2023. LIONESS enables 4D nanoscale reconstruction of living brain tissue. Nature Methods. 20(8), 1141–1142.","ama":"Danzl JG, Velicky P. LIONESS enables 4D nanoscale reconstruction of living brain tissue. Nature Methods. 2023;20(8):1141-1142. doi:10.1038/s41592-023-01937-5","chicago":"Danzl, Johann G, and Philipp Velicky. “LIONESS Enables 4D Nanoscale Reconstruction of Living Brain Tissue.” Nature Methods. Springer Nature, 2023. https://doi.org/10.1038/s41592-023-01937-5.","short":"J.G. Danzl, P. Velicky, Nature Methods 20 (2023) 1141–1142.","mla":"Danzl, Johann G., and Philipp Velicky. “LIONESS Enables 4D Nanoscale Reconstruction of Living Brain Tissue.” Nature Methods, vol. 20, no. 8, Springer Nature, 2023, pp. 1141–42, doi:10.1038/s41592-023-01937-5."},"publication":"Nature Methods","page":"1141-1142","article_type":"letter_note","issue":"8","abstract":[{"text":"We developed LIONESS, a technology that leverages improvements to optical super-resolution microscopy and prior information on sample structure via machine learning to overcome the limitations (in 3D-resolution, signal-to-noise ratio and light exposure) of optical microscopy of living biological specimens. LIONESS enables dense reconstruction of living brain tissue and morphodynamics visualization at the nanoscale.","lang":"eng"}],"type":"journal_article","oa_version":"None","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"14770","intvolume":" 20","title":"LIONESS enables 4D nanoscale reconstruction of living brain tissue","status":"public"},{"ec_funded":1,"file_date_updated":"2023-08-04T13:19:47Z","license":"https://creativecommons.org/licenses/by-nc-sa/4.0/","year":"2023","acknowledgement":"We thank Jakob Vorlaufer, Nathalie Agudelo-Dueñas, Wiebke Jahr, Andreas Wartak for microscope maintenance and troubleshooting, Caroline Kreuzinger, Anna Freeman, and Irene Erber for technical assistance and Matthias Tomschik for support with obtaining human samples. We gratefully acknowledge Eder Miguel for setting up webKnossos and Marek Šuplata for computational support and hardware control. We are grateful to Ryuichi Shigemoto and Bernd Bickel for generous support, and Michael Sixt and Scott Boyd (Stanford University) for discussions and critical reading of the manuscript. PSD95-HaloTag mice were kindly provided by Seth Grant (University of Edinburgh). We acknowledge expert support by IST Austria’s scientific computing, imaging and optics, preclinical, and lab support facilities, and by the Library and Miba machine shop.\r\nWe gratefully acknowledge funding by the following sources: \r\nAustrian Science Fund (FWF) grant I3600-B27 (JGD)\r\nAustrian Science Fund (FWF) grant DK W1232 (JGD, JMM)\r\nAustrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award (PJ)\r\nAustrian Science Funds (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27 (RH)\r\nGesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (JGD)\r\nEuropean Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 715508 – REVERSEAUTISM (GN)\r\nEuropean Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 692692 – GIANTSYN (PJ)\r\nMarie Skłodowska-Curie Actions Fellowship GA no. 665385 under the EU Horizon 2020 program (JMM, JL)\r\nMarie Skłodowska-Curie Actions Individual Fellowship 101026635 under the EU Horizon 2020 program (JFW)","publisher":"Institute of Science and Technology Austria","department":[{"_id":"JoDa"},{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"Bio"},{"_id":"RySh"}],"related_material":{"record":[{"status":"public","relation":"used_in_publication","id":"14257"}],"link":[{"url":"https://pub.ista.ac.at/group_danzl/data/CATS/","description":"Original data for Fig. 5d, Fig. 5d (N2V) and Fig. 5f-i, provided via an external link due to the large size (>10GB) of the datasets. ","relation":"research_data"}]},"contributor":[{"id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","first_name":"Julia M","last_name":"Michalska"},{"id":"46E28B80-F248-11E8-B48F-1D18A9856A87","last_name":"Lyudchik","first_name":"Julia"},{"id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2340-7431","first_name":"Philipp","last_name":"Velicky"},{"id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","last_name":"Stefanickova","first_name":"Hana"},{"last_name":"Watson","first_name":"Jake","orcid":"0000-0002-8698-3823","id":"63836096-4690-11EA-BD4E-32803DDC885E"},{"id":"9ac8f577-2357-11eb-997a-e566c5550886","first_name":"Alban","last_name":"Cenameri"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","first_name":"Christoph M","last_name":"Sommer"},{"last_name":"Amberg","first_name":"Nicole","orcid":"0000-0002-3183-8207","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Alessandro","last_name":"Venturino","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2356-9403"},{"last_name":"Roessler","first_name":"Karl"},{"last_name":"Czech","first_name":"Thomas"},{"last_name":"Höftberger","first_name":"Romana"},{"id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877","first_name":"Sandra","last_name":"Siegert"},{"last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","first_name":"Peter M","last_name":"Jonas"}],"author":[{"last_name":"Danzl","first_name":"Johann G","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G"}],"date_created":"2023-06-07T07:15:12Z","date_updated":"2024-02-21T12:18:19Z","month":"08","oa":1,"tmp":{"name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode","image":"/images/cc_by_nc_sa.png","short":"CC BY-NC-SA (4.0)"},"project":[{"grant_number":"I03600","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","name":"Optical control of synaptic function via adhesion molecules","call_identifier":"FWF"},{"_id":"26AA4EF2-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24","call_identifier":"FWF","name":"Molecular Drug Targets"},{"call_identifier":"FWF","name":"The Wittgenstein Prize","grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425"},{"name":"High content imaging to decode human immune cell interactions in health and allergic disease","_id":"23889792-32DE-11EA-91FC-C7463DDC885E"},{"call_identifier":"H2020","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","_id":"25444568-B435-11E9-9278-68D0E5697425","grant_number":"715508"},{"grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Biophysics and circuit function of a giant cortical glumatergic synapse"},{"name":"International IST Doctoral Program","call_identifier":"H2020","grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","name":"Synaptic computations of the hippocampal CA3 circuitry","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","grant_number":"101026635"}],"doi":"10.15479/AT:ISTA:13126","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"type":"research_data","abstract":[{"lang":"eng","text":"Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here, we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanometer synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS uses fixation-compatible extracellular labeling and optical imaging, including stimulated emission depletion or expansion microscopy, to comprehensively delineate cellular structures. It enables three-dimensional reconstruction of single synapses and mapping of synaptic connectivity by identification and analysis of putative synaptic cleft regions. Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed and quantified the synaptic input and output structure of identified neurons. 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Nature Physics. 19, 1916–1926."},"article_type":"original","page":"1916-1926","date_published":"2023-12-01T00:00:00Z","scopus_import":"1","day":"01","has_accepted_license":"1","article_processing_charge":"Yes (in subscription journal)","_id":"13314","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["530"],"status":"public","title":"Chiral and nematic phases of flexible active filaments","intvolume":" 19","file":[{"access_level":"open_access","file_name":"2023_NaturePhysics_Dunajova.pdf","content_type":"application/pdf","file_size":22471673,"creator":"dernst","relation":"main_file","file_id":"14916","checksum":"bc7673ca07d37309013a86166577b2f7","success":1,"date_updated":"2024-01-30T14:28:30Z","date_created":"2024-01-30T14:28:30Z"}],"oa_version":"Published Version","type":"journal_article","abstract":[{"text":"The emergence of large-scale order in self-organized systems relies on local interactions between individual components. During bacterial cell division, FtsZ—a prokaryotic homologue of the eukaryotic protein tubulin—polymerizes into treadmilling filaments that further organize into a cytoskeletal ring. In vitro, FtsZ filaments can form dynamic chiral assemblies. However, how the active and passive properties of individual filaments relate to these large-scale self-organized structures remains poorly understood. Here we connect single-filament properties with the mesoscopic scale by combining minimal active matter simulations and biochemical reconstitution experiments. We show that the density and flexibility of active chiral filaments define their global order. At intermediate densities, curved, flexible filaments organize into chiral rings and polar bands. An effectively nematic organization dominates for high densities and for straight, mutant filaments with increased rigidity. Our predicted phase diagram quantitatively captures these features, demonstrating how the flexibility, density and chirality of the active filaments affect their collective behaviour. Our findings shed light on the fundamental properties of active chiral matter and explain how treadmilling FtsZ filaments organize during bacterial cell division.","lang":"eng"}]},{"scopus_import":"1","day":"31","article_processing_charge":"Yes (in subscription journal)","publication":"Nature Biotechnology","citation":{"apa":"Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri, A., … Danzl, J. G. (2023). Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology. Springer Nature. https://doi.org/10.1038/s41587-023-01911-8","ieee":"J. M. Michalska et al., “Imaging brain tissue architecture across millimeter to nanometer scales,” Nature Biotechnology. Springer Nature, 2023.","ista":"Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer CM, Amberg N, Venturino A, Roessler K, Czech T, Höftberger R, Siegert S, Novarino G, Jonas PM, Danzl JG. 2023. Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology.","ama":"Michalska JM, Lyudchik J, Velicky P, et al. Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology. 2023. doi:10.1038/s41587-023-01911-8","chicago":"Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake Watson, Alban Cenameri, Christoph M Sommer, et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” Nature Biotechnology. Springer Nature, 2023. https://doi.org/10.1038/s41587-023-01911-8.","short":"J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri, C.M. Sommer, N. Amberg, A. Venturino, K. Roessler, T. Czech, R. Höftberger, S. Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, Nature Biotechnology (2023).","mla":"Michalska, Julia M., et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” Nature Biotechnology, Springer Nature, 2023, doi:10.1038/s41587-023-01911-8."},"article_type":"original","date_published":"2023-08-31T00:00:00Z","type":"journal_article","abstract":[{"lang":"eng","text":"Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanometer synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS uses fixation-compatible extracellular labeling and optical imaging, including stimulated emission depletion or expansion microscopy, to comprehensively delineate cellular structures. It enables three-dimensional reconstruction of single synapses and mapping of synaptic connectivity by identification and analysis of putative synaptic cleft regions. Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed and quantified the synaptic input and output structure of identified neurons. We furthermore demonstrate applicability to clinically derived human tissue samples, including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing the cellular architecture of brain tissue in health and disease."}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"14257","status":"public","title":"Imaging brain tissue architecture across millimeter to nanometer scales","oa_version":"Published Version","month":"08","publication_identifier":{"eissn":["1546-1696"],"issn":["1087-0156"]},"external_id":{"isi":["001065254200001"]},"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1038/s41587-023-01911-8"}],"oa":1,"isi":1,"quality_controlled":"1","project":[{"name":"Optical control of synaptic function via adhesion molecules","call_identifier":"FWF","grant_number":"I03600","_id":"265CB4D0-B435-11E9-9278-68D0E5697425"},{"grant_number":"W1232-B24","_id":"2548AE96-B435-11E9-9278-68D0E5697425","name":"Molecular Drug Targets","call_identifier":"FWF"},{"name":"The Wittgenstein Prize","call_identifier":"FWF","grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425"},{"name":"High content imaging to decode human immune cell interactions in health and allergic disease","_id":"23889792-32DE-11EA-91FC-C7463DDC885E"},{"_id":"25444568-B435-11E9-9278-68D0E5697425","grant_number":"715508","call_identifier":"H2020","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models"},{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","call_identifier":"H2020"},{"call_identifier":"H2020","name":"International IST Doctoral Program","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385"},{"name":"Synaptic computations of the hippocampal CA3 circuitry","call_identifier":"H2020","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","grant_number":"101026635"}],"doi":"10.1038/s41587-023-01911-8","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"language":[{"iso":"eng"}],"ec_funded":1,"year":"2023","acknowledgement":"We thank J. Vorlaufer, N. Agudelo-Dueñas, W. Jahr and A. Wartak for microscope maintenance and troubleshooting; C. Kreuzinger, A. Freeman and I. Erber for technical assistance; and M. Tomschik for support with obtaining human samples. We gratefully acknowledge E. Miguel for setting up webKnossos and M. Šuplata for computational support and hardware control. We are grateful to R. Shigemoto and B. Bickel for generous support and M. Sixt and S. Boyd (Stanford University) for discussions and critical reading of the paper. PSD95-HaloTag mice were kindly provided by S. Grant (University of Edinburgh). We acknowledge expert support by Institute of Science and Technology Austria’s scientific computing, imaging and optics, preclinical and lab support facilities and by the Miba machine shop and library. We gratefully acknowledge funding by the following sources: Austrian Science Fund (FWF) grant I3600-B27 (J.G.D.); Austrian Science Fund (FWF) grant DK W1232 (J.G.D. and J.M.M.); Austrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award (P.J.); Austrian Science Fund (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27 (R.H.); Gesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (J.G.D.); European Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 715508 – REVERSEAUTISM (G.N.); European Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 692692 – GIANTSYN (P.J.); Marie Skłodowska-Curie Actions Fellowship GA no. 665385 under the EU Horizon 2020 program (J.M.M. and J.L.); and Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.).","publication_status":"epub_ahead","publisher":"Springer Nature","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"},{"_id":"Bio"},{"_id":"RySh"}],"author":[{"full_name":"Michalska, Julia M","orcid":"0000-0003-3862-1235","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","last_name":"Michalska","first_name":"Julia M"},{"full_name":"Lyudchik, Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","first_name":"Julia","last_name":"Lyudchik"},{"full_name":"Velicky, Philipp","orcid":"0000-0002-2340-7431","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","last_name":"Velicky","first_name":"Philipp"},{"last_name":"Korinkova","first_name":"Hana","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","full_name":"Korinkova, Hana"},{"id":"63836096-4690-11EA-BD4E-32803DDC885E","orcid":"0000-0002-8698-3823","first_name":"Jake","last_name":"Watson","full_name":"Watson, Jake"},{"full_name":"Cenameri, Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886","last_name":"Cenameri","first_name":"Alban"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","first_name":"Christoph M","last_name":"Sommer","full_name":"Sommer, Christoph M"},{"id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3183-8207","first_name":"Nicole","last_name":"Amberg","full_name":"Amberg, Nicole"},{"full_name":"Venturino, Alessandro","last_name":"Venturino","first_name":"Alessandro","orcid":"0000-0003-2356-9403","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Roessler, Karl","last_name":"Roessler","first_name":"Karl"},{"last_name":"Czech","first_name":"Thomas","full_name":"Czech, Thomas"},{"last_name":"Höftberger","first_name":"Romana","full_name":"Höftberger, Romana"},{"id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877","first_name":"Sandra","last_name":"Siegert","full_name":"Siegert, Sandra"},{"full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino"},{"full_name":"Jonas, Peter M","last_name":"Jonas","first_name":"Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Danzl","first_name":"Johann G","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G"}],"related_material":{"link":[{"relation":"software","url":"https://github.com/danzllab/CATS"}],"record":[{"status":"public","relation":"research_data","id":"13126"}]},"date_created":"2023-09-03T22:01:15Z","date_updated":"2024-02-21T12:18:18Z"},{"file_date_updated":"2023-07-27T22:30:54Z","ec_funded":1,"year":"2023","publication_status":"published","publisher":"Institute of Science and Technology Austria","department":[{"_id":"GradSch"},{"_id":"JoDa"}],"author":[{"full_name":"Michalska, Julia M","last_name":"Michalska","first_name":"Julia M","orcid":"0000-0003-3862-1235","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87"}],"related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"11943"},{"id":"11950","relation":"part_of_dissertation","status":"public"}]},"date_created":"2023-01-31T15:10:53Z","date_updated":"2023-08-31T12:26:58Z","month":"01","publication_identifier":{"issn":["2663-337X"],"isbn":[" 978-3-99078-026-8"]},"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"project":[{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385","name":"International IST Doctoral Program","call_identifier":"H2020"},{"grant_number":"W1232-B24","_id":"26AA4EF2-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Molecular Drug Targets"}],"doi":"10.15479/at:ista:12470","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"},{"_id":"PreCl"},{"_id":"EM-Fac"},{"_id":"M-Shop"},{"_id":"ScienComp"}],"degree_awarded":"PhD","supervisor":[{"full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","first_name":"Johann G","last_name":"Danzl"}],"language":[{"iso":"eng"}],"type":"dissertation","alternative_title":["ISTA Thesis"],"abstract":[{"lang":"eng","text":"The brain is an exceptionally sophisticated organ consisting of billions of cells and trillions of \r\nconnections that orchestrate our cognition and behavior. To decode its complex connectivity, it is \r\npivotal to disentangle its intricate architecture spanning from cm-sized circuits down to tens of \r\nnm-small synapses.\r\nTo achieve this goal, I developed CATS – Comprehensive Analysis of nervous Tissue across \r\nScales, a versatile toolbox for obtaining a holistic view of nervous tissue context with (super\u0002resolution) fluorescence microscopy. CATS combines comprehensive labeling of the extracellular\r\nspace, that is compatible with chemical fixation, with information on molecular markers, super\u0002resolved data acquisition and machine-learning based data analysis for segmentation and synapse \r\nidentification.\r\nI used CATS to analyze key features of nervous tissue connectivity, ranging from whole tissue \r\narchitecture, neuronal in- and output-fields, down to synapse morphology.\r\nFocusing on the hippocampal circuitry, I quantified synaptic transmission properties of mossy \r\nfiber boutons and analyzed the connectivity pattern of dentate gyrus granule cells with CA3 \r\npyramidal neurons. This shows that CATS is a viable tool to study hallmarks of neuronal \r\nconnectivity with light microscopy."}],"_id":"12470","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","title":"A versatile toolbox for the comprehensive analysis of nervous tissue organization with light microscopy","ddc":["610"],"status":"public","oa_version":"Published Version","file":[{"embargo":"2023-07-09","file_id":"12471","relation":"main_file","checksum":"1a2306e5f59f52df598e7ecfadf921ac","date_created":"2023-01-31T15:11:42Z","date_updated":"2023-07-27T22:30:54Z","access_level":"open_access","file_name":"20230109_PhD_thesis_JM_final.pdf","creator":"cchlebak","file_size":41771714,"content_type":"application/pdf"},{"date_created":"2023-01-31T15:11:51Z","date_updated":"2023-07-10T22:30:04Z","checksum":"0bebbdee0773443959e1f6ab8caf281f","relation":"source_file","file_id":"12472","file_size":66983464,"content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","creator":"cchlebak","embargo_to":"open_access","file_name":"20230109_PhD_thesis_JM_final.docx","access_level":"closed"}],"day":"09","has_accepted_license":"1","article_processing_charge":"No","citation":{"ista":"Michalska JM. 2023. A versatile toolbox for the comprehensive analysis of nervous tissue organization with light microscopy. Institute of Science and Technology Austria.","ieee":"J. M. Michalska, “A versatile toolbox for the comprehensive analysis of nervous tissue organization with light microscopy,” Institute of Science and Technology Austria, 2023.","apa":"Michalska, J. M. (2023). A versatile toolbox for the comprehensive analysis of nervous tissue organization with light microscopy. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:12470","ama":"Michalska JM. A versatile toolbox for the comprehensive analysis of nervous tissue organization with light microscopy. 2023. doi:10.15479/at:ista:12470","chicago":"Michalska, Julia M. “A Versatile Toolbox for the Comprehensive Analysis of Nervous Tissue Organization with Light Microscopy.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:12470.","mla":"Michalska, Julia M. A Versatile Toolbox for the Comprehensive Analysis of Nervous Tissue Organization with Light Microscopy. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:12470.","short":"J.M. Michalska, A Versatile Toolbox for the Comprehensive Analysis of Nervous Tissue Organization with Light Microscopy, Institute of Science and Technology Austria, 2023."},"page":"201","date_published":"2023-01-09T00:00:00Z"},{"oa_version":"Published Version","file":[{"date_created":"2022-08-26T11:51:40Z","date_updated":"2022-08-26T11:51:40Z","checksum":"405936d9e4d33625d80c093c9713a91f","success":1,"relation":"main_file","file_id":"11990","content_type":"application/pdf","file_size":5910357,"creator":"dernst","file_name":"2022_NatureCommunications_BenSimon.pdf","access_level":"open_access"}],"intvolume":" 13","status":"public","title":"A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory","ddc":["570"],"_id":"11951","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","abstract":[{"lang":"eng","text":"The mammalian hippocampal formation (HF) plays a key role in several higher brain functions, such as spatial coding, learning and memory. Its simple circuit architecture is often viewed as a trisynaptic loop, processing input originating from the superficial layers of the entorhinal cortex (EC) and sending it back to its deeper layers. Here, we show that excitatory neurons in layer 6b of the mouse EC project to all sub-regions comprising the HF and receive input from the CA1, thalamus and claustrum. Furthermore, their output is characterized by unique slow-decaying excitatory postsynaptic currents capable of driving plateau-like potentials in their postsynaptic targets. Optogenetic inhibition of the EC-6b pathway affects spatial coding in CA1 pyramidal neurons, while cell ablation impairs not only acquisition of new spatial memories, but also degradation of previously acquired ones. Our results provide evidence of a functional role for cortical layer 6b neurons in the adult brain."}],"type":"journal_article","date_published":"2022-08-16T00:00:00Z","article_type":"original","citation":{"apa":"Ben Simon, Y., Käfer, K., Velicky, P., Csicsvari, J. L., Danzl, J. G., & Jonas, P. M. (2022). A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-022-32559-8","ieee":"Y. Ben Simon, K. Käfer, P. Velicky, J. L. Csicsvari, J. G. Danzl, and P. M. Jonas, “A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory,” Nature Communications, vol. 13. Springer Nature, 2022.","ista":"Ben Simon Y, Käfer K, Velicky P, Csicsvari JL, Danzl JG, Jonas PM. 2022. A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory. Nature Communications. 13, 4826.","ama":"Ben Simon Y, Käfer K, Velicky P, Csicsvari JL, Danzl JG, Jonas PM. A direct excitatory projection from entorhinal layer 6b neurons to the hippocampus contributes to spatial coding and memory. Nature Communications. 2022;13. doi:10.1038/s41467-022-32559-8","chicago":"Ben Simon, Yoav, Karola Käfer, Philipp Velicky, Jozsef L Csicsvari, Johann G Danzl, and Peter M Jonas. “A Direct Excitatory Projection from Entorhinal Layer 6b Neurons to the Hippocampus Contributes to Spatial Coding and Memory.” Nature Communications. Springer Nature, 2022. https://doi.org/10.1038/s41467-022-32559-8.","short":"Y. Ben Simon, K. Käfer, P. Velicky, J.L. Csicsvari, J.G. Danzl, P.M. Jonas, Nature Communications 13 (2022).","mla":"Ben Simon, Yoav, et al. “A Direct Excitatory Projection from Entorhinal Layer 6b Neurons to the Hippocampus Contributes to Spatial Coding and Memory.” Nature Communications, vol. 13, 4826, Springer Nature, 2022, doi:10.1038/s41467-022-32559-8."},"publication":"Nature Communications","article_processing_charge":"No","has_accepted_license":"1","day":"16","keyword":["General Physics and Astronomy","General Biochemistry","Genetics and Molecular Biology","General Chemistry","Multidisciplinary"],"volume":13,"date_created":"2022-08-24T08:25:50Z","date_updated":"2023-08-03T13:01:19Z","author":[{"id":"43DF3136-F248-11E8-B48F-1D18A9856A87","last_name":"Ben Simon","first_name":"Yoav","full_name":"Ben Simon, Yoav"},{"full_name":"Käfer, Karola","id":"2DAA49AA-F248-11E8-B48F-1D18A9856A87","last_name":"Käfer","first_name":"Karola"},{"full_name":"Velicky, Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2340-7431","first_name":"Philipp","last_name":"Velicky"},{"orcid":"0000-0002-5193-4036","id":"3FA14672-F248-11E8-B48F-1D18A9856A87","last_name":"Csicsvari","first_name":"Jozsef L","full_name":"Csicsvari, Jozsef L"},{"full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","first_name":"Johann G","last_name":"Danzl"},{"orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","first_name":"Peter M","full_name":"Jonas, Peter M"}],"publisher":"Springer Nature","department":[{"_id":"JoCs"},{"_id":"PeJo"},{"_id":"JoDa"}],"publication_status":"published","acknowledgement":"We thank F. Marr and A. Schlögl for technical assistance, E. Kralli-Beller for manuscript editing, as well as C. Sommer and the Imaging and Optics Facility of the Institute of Science and Technology Austria (ISTA) for image analysis scripts and microscopy support. We extend our gratitude to J. Wallenschus and D. Rangel Guerrero for technical assistance acquiring single-unit data and I. Gridchyn for help with single-unit clustering. Finally, we also thank B. Suter for discussions, A. Saunders, M. Jösch, and H. Monyer for critically reading earlier versions of the manuscript, C. Petersen for sharing clearing protocols, and the Scientific Service Units of ISTA for efficient support. This project was funded by the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (ERC advanced grant No 692692 to P.J.) and the Fond zur Förderung der Wissenschaftlichen Forschung (Z 312-B27, Wittgenstein award for P.J. and I3600-B27 for J.G.D. and P.V.).","year":"2022","ec_funded":1,"file_date_updated":"2022-08-26T11:51:40Z","article_number":"4826","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"SSU"}],"doi":"10.1038/s41467-022-32559-8","project":[{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","call_identifier":"H2020"},{"name":"Optical control of synaptic function via adhesion molecules","call_identifier":"FWF","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","grant_number":"I03600"},{"name":"The Wittgenstein Prize","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312"}],"quality_controlled":"1","isi":1,"external_id":{"isi":["000841396400008"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"publication_identifier":{"issn":["2041-1723"]},"month":"08"},{"abstract":[{"lang":"eng","text":"Complex wiring between neurons underlies the information-processing network enabling all brain functions, including cognition and memory. For understanding how the network is structured, processes information, and changes over time, comprehensive visualization of the architecture of living brain tissue with its cellular and molecular components would open up major opportunities. However, electron microscopy (EM) provides nanometre-scale resolution required for full in-silico reconstruction1–5, yet is limited to fixed specimens and static representations. Light microscopy allows live observation, with super-resolution approaches6–12 facilitating nanoscale visualization, but comprehensive 3D-reconstruction of living brain tissue has been hindered by tissue photo-burden, photobleaching, insufficient 3D-resolution, and inadequate signal-to-noise ratio (SNR). Here we demonstrate saturated reconstruction of living brain tissue. We developed an integrated imaging and analysis technology, adapting stimulated emission depletion (STED) microscopy6,13 in extracellularly labelled tissue14 for high SNR and near-isotropic resolution. Centrally, a two-stage deep-learning approach leveraged previously obtained information on sample structure to drastically reduce photo-burden and enable automated volumetric reconstruction down to single synapse level. Live reconstruction provides unbiased analysis of tissue architecture across time in relation to functional activity and targeted activation, and contextual understanding of molecular labelling. This adoptable technology will facilitate novel insights into the dynamic functional architecture of living brain tissue."}],"type":"preprint","date_updated":"2024-03-28T23:30:20Z","date_created":"2022-08-23T11:07:59Z","oa_version":"Preprint","author":[{"full_name":"Velicky, Philipp","last_name":"Velicky","first_name":"Philipp","orcid":"0000-0002-2340-7431","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Miguel Villalba, Eder","orcid":"0000-0001-5665-0430","id":"3FB91342-F248-11E8-B48F-1D18A9856A87","last_name":"Miguel Villalba","first_name":"Eder"},{"full_name":"Michalska, Julia M","orcid":"0000-0003-3862-1235","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","last_name":"Michalska","first_name":"Julia M"},{"first_name":"Donglai","last_name":"Wei","full_name":"Wei, Donglai"},{"first_name":"Zudi","last_name":"Lin","full_name":"Lin, Zudi"},{"orcid":"0000-0002-8698-3823","id":"63836096-4690-11EA-BD4E-32803DDC885E","last_name":"Watson","first_name":"Jake","full_name":"Watson, Jake"},{"first_name":"Jakob","last_name":"Troidl","full_name":"Troidl, Jakob"},{"last_name":"Beyer","first_name":"Johanna","full_name":"Beyer, Johanna"},{"full_name":"Ben Simon, Yoav","id":"43DF3136-F248-11E8-B48F-1D18A9856A87","first_name":"Yoav","last_name":"Ben Simon"},{"orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","last_name":"Sommer","first_name":"Christoph M","full_name":"Sommer, Christoph M"},{"full_name":"Jahr, Wiebke","first_name":"Wiebke","last_name":"Jahr","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Cenameri, Alban","last_name":"Cenameri","first_name":"Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886"},{"first_name":"Johannes","last_name":"Broichhagen","full_name":"Broichhagen, Johannes"},{"full_name":"Grant, Seth G. N.","last_name":"Grant","first_name":"Seth G. N."},{"full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","first_name":"Peter M","last_name":"Jonas"},{"full_name":"Novarino, Gaia","first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178"},{"full_name":"Pfister, Hanspeter","last_name":"Pfister","first_name":"Hanspeter"},{"first_name":"Bernd","last_name":"Bickel","id":"49876194-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6511-9385","full_name":"Bickel, Bernd"},{"full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","first_name":"Johann G","last_name":"Danzl"}],"related_material":{"record":[{"id":"12470","status":"public","relation":"dissertation_contains"}]},"status":"public","publication_status":"submitted","title":"Saturated reconstruction of living brain tissue","publisher":"Cold Spring Harbor Laboratory","department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"11943","year":"2022","month":"05","day":"09","article_processing_charge":"No","language":[{"iso":"eng"}],"date_published":"2022-05-09T00:00:00Z","doi":"10.1101/2022.03.16.484431","publication":"bioRxiv","citation":{"short":"P. Velicky, E. Miguel Villalba, J.M. Michalska, D. Wei, Z. Lin, J. Watson, J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri, J. Broichhagen, S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel, J.G. Danzl, BioRxiv (n.d.).","mla":"Velicky, Philipp, et al. “Saturated Reconstruction of Living Brain Tissue.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2022.03.16.484431.","chicago":"Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Donglai Wei, Zudi Lin, Jake Watson, Jakob Troidl, et al. “Saturated Reconstruction of Living Brain Tissue.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2022.03.16.484431.","ama":"Velicky P, Miguel Villalba E, Michalska JM, et al. Saturated reconstruction of living brain tissue. bioRxiv. doi:10.1101/2022.03.16.484431","apa":"Velicky, P., Miguel Villalba, E., Michalska, J. M., Wei, D., Lin, Z., Watson, J., … Danzl, J. G. (n.d.). Saturated reconstruction of living brain tissue. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2022.03.16.484431","ieee":"P. Velicky et al., “Saturated reconstruction of living brain tissue,” bioRxiv. Cold Spring Harbor Laboratory.","ista":"Velicky P, Miguel Villalba E, Michalska JM, Wei D, Lin Z, Watson J, Troidl J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen J, Grant SGN, Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. Saturated reconstruction of living brain tissue. bioRxiv, 10.1101/2022.03.16.484431."},"oa":1,"main_file_link":[{"url":"https://doi.org/10.1101/2022.03.16.484431","open_access":"1"}]},{"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"11950","year":"2022","publication_status":"submitted","title":"Uncovering brain tissue architecture across scales with super-resolution light microscopy","status":"public","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"}],"publisher":"Cold Spring Harbor Laboratory","author":[{"id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3862-1235","first_name":"Julia M","last_name":"Michalska","full_name":"Michalska, Julia M"},{"id":"46E28B80-F248-11E8-B48F-1D18A9856A87","first_name":"Julia","last_name":"Lyudchik","full_name":"Lyudchik, Julia"},{"first_name":"Philipp","last_name":"Velicky","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2340-7431","full_name":"Velicky, Philipp"},{"full_name":"Korinkova, Hana","last_name":"Korinkova","first_name":"Hana","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed"},{"full_name":"Watson, Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E","orcid":"0000-0002-8698-3823","first_name":"Jake","last_name":"Watson"},{"full_name":"Cenameri, Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886","last_name":"Cenameri","first_name":"Alban"},{"full_name":"Sommer, Christoph M","first_name":"Christoph M","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105"},{"orcid":"0000-0003-2356-9403","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","last_name":"Venturino","first_name":"Alessandro","full_name":"Venturino, Alessandro"},{"full_name":"Roessler, Karl","last_name":"Roessler","first_name":"Karl"},{"first_name":"Thomas","last_name":"Czech","full_name":"Czech, Thomas"},{"first_name":"Sandra","last_name":"Siegert","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877","full_name":"Siegert, Sandra"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino","full_name":"Novarino, Gaia"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","first_name":"Peter M","last_name":"Jonas","full_name":"Jonas, Peter M"},{"orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","last_name":"Danzl","first_name":"Johann G","full_name":"Danzl, Johann G"}],"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"12470"}]},"date_updated":"2024-03-28T23:30:20Z","date_created":"2022-08-24T08:24:52Z","oa_version":"Preprint","type":"preprint","abstract":[{"lang":"eng","text":"Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanoscopic synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS leverages fixation-compatible extracellular labeling and advanced optical readout, in particular stimulated-emission depletion and expansion microscopy, to comprehensively delineate cellular structures. It enables 3D-reconstructing single synapses and mapping synaptic connectivity by identification and tailored analysis of putative synaptic cleft regions. Applying CATS to the hippocampal mossy fiber circuitry, we demonstrate its power to reveal the system’s molecularly informed ultrastructure across spatial scales and assess local connectivity by reconstructing and quantifying the synaptic input and output structure of identified neurons."}],"publication":"bioRxiv","oa":1,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2022.08.17.504272"}],"citation":{"short":"J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri, C.M. Sommer, A. Venturino, K. Roessler, T. Czech, S. Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, BioRxiv (n.d.).","mla":"Michalska, Julia M., et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2022.08.17.504272.","chicago":"Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake Watson, Alban Cenameri, Christoph M Sommer, et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2022.08.17.504272.","ama":"Michalska JM, Lyudchik J, Velicky P, et al. Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv. doi:10.1101/2022.08.17.504272","apa":"Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri, A., … Danzl, J. G. (n.d.). Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2022.08.17.504272","ieee":"J. M. Michalska et al., “Uncovering brain tissue architecture across scales with super-resolution light microscopy,” bioRxiv. Cold Spring Harbor Laboratory.","ista":"Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer CM, Venturino A, Roessler K, Czech T, Siegert S, Novarino G, Jonas PM, Danzl JG. Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv, 10.1101/2022.08.17.504272."},"doi":"10.1101/2022.08.17.504272","date_published":"2022-08-18T00:00:00Z","language":[{"iso":"eng"}],"month":"08","day":"18","article_processing_charge":"No"},{"has_accepted_license":"1","article_processing_charge":"Yes","day":"05","keyword":["General Biochemistry","Genetics and Molecular Biology"],"date_published":"2022-04-05T00:00:00Z","article_type":"original","citation":{"ama":"Villa CE, Cheroni C, Dotter C, et al. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. Cell Reports. 2022;39(1). doi:10.1016/j.celrep.2022.110615","apa":"Villa, C. E., Cheroni, C., Dotter, C., López-Tóbon, A., Oliveira, B., Sacco, R., … Novarino, G. (2022). CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. Cell Reports. Elsevier. https://doi.org/10.1016/j.celrep.2022.110615","ieee":"C. E. Villa et al., “CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories,” Cell Reports, vol. 39, no. 1. Elsevier, 2022.","ista":"Villa CE, Cheroni C, Dotter C, López-Tóbon A, Oliveira B, Sacco R, Yahya AÇ, Morandell J, Gabriele M, Tavakoli M, Lyudchik J, Sommer CM, Gabitto M, Danzl JG, Testa G, Novarino G. 2022. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. Cell Reports. 39(1), 110615.","short":"C.E. Villa, C. Cheroni, C. Dotter, A. López-Tóbon, B. Oliveira, R. Sacco, A.Ç. Yahya, J. Morandell, M. Gabriele, M. Tavakoli, J. Lyudchik, C.M. Sommer, M. Gabitto, J.G. Danzl, G. Testa, G. Novarino, Cell Reports 39 (2022).","mla":"Villa, Carlo Emanuele, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” Cell Reports, vol. 39, no. 1, 110615, Elsevier, 2022, doi:10.1016/j.celrep.2022.110615.","chicago":"Villa, Carlo Emanuele, Cristina Cheroni, Christoph Dotter, Alejandro López-Tóbon, Bárbara Oliveira, Roberto Sacco, Aysan Çerağ Yahya, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” Cell Reports. Elsevier, 2022. https://doi.org/10.1016/j.celrep.2022.110615."},"publication":"Cell Reports","issue":"1","abstract":[{"text":"Mutations in the chromodomain helicase DNA-binding 8 (CHD8) gene are a frequent cause of autism spectrum disorder (ASD). While its phenotypic spectrum often encompasses macrocephaly, implicating cortical abnormalities, how CHD8 haploinsufficiency affects neurodevelopmental is unclear. Here, employing human cerebral organoids, we find that CHD8 haploinsufficiency disrupted neurodevelopmental trajectories with an accelerated and delayed generation of, respectively, inhibitory and excitatory neurons that yields, at days 60 and 120, symmetrically opposite expansions in their proportions. This imbalance is consistent with an enlargement of cerebral organoids as an in vitro correlate of patients’ macrocephaly. Through an isogenic design of patient-specific mutations and mosaic organoids, we define genotype-phenotype relationships and uncover their cell-autonomous nature. Our results define cell-type-specific CHD8-dependent molecular defects related to an abnormal program of proliferation and alternative splicing. By identifying cell-type-specific effects of CHD8 mutations, our study uncovers reproducible developmental alterations that may be employed for neurodevelopmental disease modeling.","lang":"eng"}],"type":"journal_article","oa_version":"Published Version","file":[{"checksum":"b4e8d68f0268dec499af333e6fd5d8e1","success":1,"date_created":"2022-04-15T09:06:25Z","date_updated":"2022-04-15T09:06:25Z","relation":"main_file","file_id":"11164","content_type":"application/pdf","file_size":"7808644","creator":"dernst","access_level":"open_access","file_name":"2022_CellReports_Villa.pdf"}],"intvolume":" 39","ddc":["570"],"title":"CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories","status":"public","_id":"11160","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","publication_identifier":{"issn":["2211-1247"]},"month":"04","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"doi":"10.1016/j.celrep.2022.110615","project":[{"call_identifier":"H2020","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","grant_number":"715508","_id":"25444568-B435-11E9-9278-68D0E5697425"},{"grant_number":"I04205","_id":"2690FEAC-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Identification of converging Molecular Pathways Across Chromatinopathies as Targets for Therapy"}],"isi":1,"quality_controlled":"1","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"external_id":{"pmid":["35385734"],"isi":["000785983900003"]},"ec_funded":1,"file_date_updated":"2022-04-15T09:06:25Z","article_number":"110615","volume":39,"date_updated":"2024-03-28T23:30:45Z","date_created":"2022-04-15T09:03:10Z","related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"12364"}]},"author":[{"full_name":"Villa, Carlo Emanuele","last_name":"Villa","first_name":"Carlo Emanuele"},{"full_name":"Cheroni, Cristina","first_name":"Cristina","last_name":"Cheroni"},{"full_name":"Dotter, Christoph","last_name":"Dotter","first_name":"Christoph","orcid":"0000-0002-9033-9096","id":"4C66542E-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Alejandro","last_name":"López-Tóbon","full_name":"López-Tóbon, Alejandro"},{"full_name":"Oliveira, Bárbara","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","last_name":"Oliveira","first_name":"Bárbara"},{"full_name":"Sacco, Roberto","id":"42C9F57E-F248-11E8-B48F-1D18A9856A87","last_name":"Sacco","first_name":"Roberto"},{"first_name":"Aysan Çerağ","last_name":"Yahya","id":"365A65F8-F248-11E8-B48F-1D18A9856A87","full_name":"Yahya, Aysan Çerağ"},{"full_name":"Morandell, Jasmin","first_name":"Jasmin","last_name":"Morandell","id":"4739D480-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Gabriele, Michele","first_name":"Michele","last_name":"Gabriele"},{"full_name":"Tavakoli, Mojtaba","orcid":"0000-0002-7667-6854","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","last_name":"Tavakoli","first_name":"Mojtaba"},{"last_name":"Lyudchik","first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","full_name":"Lyudchik, Julia"},{"full_name":"Sommer, Christoph M","first_name":"Christoph M","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105"},{"full_name":"Gabitto, Mariano","first_name":"Mariano","last_name":"Gabitto"},{"full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","last_name":"Danzl","first_name":"Johann G"},{"full_name":"Testa, Giuseppe","first_name":"Giuseppe","last_name":"Testa"},{"full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino"}],"department":[{"_id":"JoDa"},{"_id":"GaNo"}],"publisher":"Elsevier","publication_status":"published","pmid":1,"year":"2022","acknowledgement":"We thank Farnaz Freeman for technical assistance. This research was supported by the Scientific Service Units (SSU) of IST Austria through resources provided by the Bioimaging Facility (BIF) and the Life Science Facility (LSF). This work supported by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 to G.N. (REVERSEAUTISM) and grant 825759 to G.T. (ENDpoiNTs); the Fondazione Cariplo 2017-0886 to A.L.T.; E-Rare-3 JTC 2018 IMPACT to M. Gabriele; and the Austrian Science Fund FWF I 4205-B to G.N. Graphical abstract and figures were created using BioRender.com."},{"doi":"10.1016/bs.mcb.2020.04.016","date_published":"2021-01-01T00:00:00Z","language":[{"iso":"eng"}],"external_id":{"pmid":["33478696"]},"citation":{"ieee":"S. M. Truckenbrodt and S. O. Rizzoli, “Simple multi-color super-resolution by X10 microscopy,” in Methods in Cell Biology, vol. 161, Elsevier, 2021, pp. 33–56.","apa":"Truckenbrodt, S. M., & Rizzoli, S. O. (2021). Simple multi-color super-resolution by X10 microscopy. In Methods in Cell Biology (Vol. 161, pp. 33–56). Elsevier. https://doi.org/10.1016/bs.mcb.2020.04.016","ista":"Truckenbrodt SM, Rizzoli SO. 2021.Simple multi-color super-resolution by X10 microscopy. In: Methods in Cell Biology. vol. 161, 33–56.","ama":"Truckenbrodt SM, Rizzoli SO. Simple multi-color super-resolution by X10 microscopy. In: Methods in Cell Biology. Vol 161. Elsevier; 2021:33-56. doi:10.1016/bs.mcb.2020.04.016","chicago":"Truckenbrodt, Sven M, and Silvio O. Rizzoli. “Simple Multi-Color Super-Resolution by X10 Microscopy.” In Methods in Cell Biology, 161:33–56. Elsevier, 2021. https://doi.org/10.1016/bs.mcb.2020.04.016.","short":"S.M. Truckenbrodt, S.O. Rizzoli, in:, Methods in Cell Biology, Elsevier, 2021, pp. 33–56.","mla":"Truckenbrodt, Sven M., and Silvio O. Rizzoli. “Simple Multi-Color Super-Resolution by X10 Microscopy.” Methods in Cell Biology, vol. 161, Elsevier, 2021, pp. 33–56, doi:10.1016/bs.mcb.2020.04.016."},"publication":"Methods in Cell Biology","page":"33-56","quality_controlled":"1","publication_identifier":{"issn":["0091-679X"],"isbn":["978012820807-6"]},"article_processing_charge":"No","day":"01","month":"01","scopus_import":"1","author":[{"id":"45812BD4-F248-11E8-B48F-1D18A9856A87","last_name":"Truckenbrodt","first_name":"Sven M","full_name":"Truckenbrodt, Sven M"},{"last_name":"Rizzoli","first_name":"Silvio O.","full_name":"Rizzoli, Silvio O."}],"volume":161,"oa_version":"None","date_created":"2020-06-07T22:00:55Z","date_updated":"2021-03-11T08:49:08Z","pmid":1,"year":"2021","_id":"7941","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"JoDa"}],"intvolume":" 161","publisher":"Elsevier","title":"Simple multi-color super-resolution by X10 microscopy","status":"public","publication_status":"published","abstract":[{"lang":"eng","text":"Expansion microscopy is a recently developed super-resolution imaging technique, which provides an alternative to optics-based methods such as deterministic approaches (e.g. STED) or stochastic approaches (e.g. PALM/STORM). The idea behind expansion microscopy is to embed the biological sample in a swellable gel, and then to expand it isotropically, thereby increasing the distance between the fluorophores. This approach breaks the diffraction barrier by simply separating the emission point-spread-functions of the fluorophores. The resolution attainable in expansion microscopy is thus directly dependent on the separation that can be achieved, i.e. on the expansion factor. The original implementation of the technique achieved an expansion factor of fourfold, for a resolution of 70–80 nm. The subsequently developed X10 method achieves an expansion factor of 10-fold, for a resolution of 25–30 nm. This technique can be implemented with minimal technical requirements on any standard fluorescence microscope, and is more easily applied for multi-color imaging than either deterministic or stochastic super-resolution approaches. This renders X10 expansion microscopy a highly promising tool for new biological discoveries, as discussed here, and as demonstrated by several recent applications."}],"type":"book_chapter"},{"external_id":{"isi":["000625600600007"],"pmid":["33674797"]},"main_file_link":[{"url":"https://doi.org/10.1038/s41592-021-01087-6","open_access":"1"}],"oa":1,"quality_controlled":"1","isi":1,"doi":"10.1038/s41592-021-01087-6","language":[{"iso":"eng"}],"month":"03","publication_identifier":{"eissn":["1548-7105"],"issn":["1548-7091"]},"acknowledgement":"We thank S. van der Walt and K. Marchuk for discussion during development. This project was funded by Packard Fellowship and Chan Zuckerberg Biohub Investigator Awards to L.W.; STROBE: A NSF Science and Technology Center; an NSF Graduate Research Fellowship awarded to H.P.; a Berkeley Institute for Data Science/UCSF Bakar Computational Health Sciences Institute Fellowship awarded to H.P. with support from the Koret Foundation, the Gordon and Betty Moore Foundation, and the Alfred P. Sloan Foundation to the University of California, Berkeley. K.W.E., B.L. and M.T. were funded by the Chan Zuckerberg Initiative and NIH grant P41GM135019.","year":"2021","pmid":1,"publication_status":"published","publisher":"Springer Nature","department":[{"_id":"JoDa"}],"author":[{"full_name":"Pinkard, Henry","first_name":"Henry","last_name":"Pinkard"},{"last_name":"Stuurman","first_name":"Nico","full_name":"Stuurman, Nico"},{"full_name":"Ivanov, Ivan E.","last_name":"Ivanov","first_name":"Ivan E."},{"full_name":"Anthony, Nicholas M.","first_name":"Nicholas M.","last_name":"Anthony"},{"full_name":"Ouyang, Wei","last_name":"Ouyang","first_name":"Wei"},{"full_name":"Li, Bin","first_name":"Bin","last_name":"Li"},{"full_name":"Yang, Bin","last_name":"Yang","first_name":"Bin"},{"full_name":"Tsuchida, Mark A.","first_name":"Mark A.","last_name":"Tsuchida"},{"last_name":"Chhun","first_name":"Bryant","full_name":"Chhun, Bryant"},{"last_name":"Zhang","first_name":"Grace","full_name":"Zhang, Grace"},{"full_name":"Mei, Ryan","first_name":"Ryan","last_name":"Mei"},{"last_name":"Anderson","first_name":"Michael","full_name":"Anderson, Michael"},{"first_name":"Douglas P.","last_name":"Shepherd","full_name":"Shepherd, Douglas P."},{"full_name":"Hunt-Isaak, Ian","last_name":"Hunt-Isaak","first_name":"Ian"},{"first_name":"Raymond L.","last_name":"Dunn","full_name":"Dunn, Raymond L."},{"id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","last_name":"Jahr","first_name":"Wiebke","full_name":"Jahr, Wiebke"},{"full_name":"Kato, Saul","last_name":"Kato","first_name":"Saul"},{"full_name":"Royer, Loïc A.","last_name":"Royer","first_name":"Loïc A."},{"full_name":"Thiagarajah, Jay R.","last_name":"Thiagarajah","first_name":"Jay R."},{"first_name":"Kevin W.","last_name":"Eliceiri","full_name":"Eliceiri, Kevin W."},{"full_name":"Lundberg, Emma","first_name":"Emma","last_name":"Lundberg"},{"first_name":"Shalin B.","last_name":"Mehta","full_name":"Mehta, Shalin B."},{"full_name":"Waller, Laura","first_name":"Laura","last_name":"Waller"}],"date_created":"2021-03-21T23:01:20Z","date_updated":"2023-08-07T14:19:08Z","volume":18,"publication":"Nature Methods","citation":{"short":"H. Pinkard, N. Stuurman, I.E. Ivanov, N.M. Anthony, W. Ouyang, B. Li, B. Yang, M.A. Tsuchida, B. Chhun, G. Zhang, R. Mei, M. Anderson, D.P. Shepherd, I. Hunt-Isaak, R.L. Dunn, W. Jahr, S. Kato, L.A. Royer, J.R. Thiagarajah, K.W. Eliceiri, E. Lundberg, S.B. Mehta, L. Waller, Nature Methods 18 (2021) 226–228.","mla":"Pinkard, Henry, et al. “Pycro-Manager: Open-Source Software for Customized and Reproducible Microscope Control.” Nature Methods, vol. 18, no. 3, Springer Nature, 2021, pp. 226–28, doi:10.1038/s41592-021-01087-6.","chicago":"Pinkard, Henry, Nico Stuurman, Ivan E. Ivanov, Nicholas M. Anthony, Wei Ouyang, Bin Li, Bin Yang, et al. “Pycro-Manager: Open-Source Software for Customized and Reproducible Microscope Control.” Nature Methods. Springer Nature, 2021. https://doi.org/10.1038/s41592-021-01087-6.","ama":"Pinkard H, Stuurman N, Ivanov IE, et al. Pycro-Manager: Open-source software for customized and reproducible microscope control. Nature Methods. 2021;18(3):226-228. doi:10.1038/s41592-021-01087-6","ieee":"H. Pinkard et al., “Pycro-Manager: Open-source software for customized and reproducible microscope control,” Nature Methods, vol. 18, no. 3. Springer Nature, pp. 226–228, 2021.","apa":"Pinkard, H., Stuurman, N., Ivanov, I. E., Anthony, N. M., Ouyang, W., Li, B., … Waller, L. (2021). Pycro-Manager: Open-source software for customized and reproducible microscope control. Nature Methods. Springer Nature. https://doi.org/10.1038/s41592-021-01087-6","ista":"Pinkard H, Stuurman N, Ivanov IE, Anthony NM, Ouyang W, Li B, Yang B, Tsuchida MA, Chhun B, Zhang G, Mei R, Anderson M, Shepherd DP, Hunt-Isaak I, Dunn RL, Jahr W, Kato S, Royer LA, Thiagarajah JR, Eliceiri KW, Lundberg E, Mehta SB, Waller L. 2021. Pycro-Manager: Open-source software for customized and reproducible microscope control. Nature Methods. 18(3), 226–228."},"article_type":"letter_note","page":"226-228","date_published":"2021-03-01T00:00:00Z","scopus_import":"1","day":"01","article_processing_charge":"No","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"9258","title":"Pycro-Manager: Open-source software for customized and reproducible microscope control","status":"public","intvolume":" 18","oa_version":"Published Version","type":"journal_article","issue":"3"},{"month":"05","publication_identifier":{"eissn":["2041-1723"]},"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000658769900010"]},"isi":1,"quality_controlled":"1","project":[{"name":"ISTplus - Postdoctoral Fellowships","call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411"},{"_id":"25444568-B435-11E9-9278-68D0E5697425","grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020"},{"name":"Molecular Drug Targets","call_identifier":"FWF","grant_number":"W1232-B24","_id":"2548AE96-B435-11E9-9278-68D0E5697425"},{"name":"Neural stem cells in autism and epilepsy","_id":"05A0D778-7A3F-11EA-A408-12923DDC885E","grant_number":"F07807"},{"name":"Optical control of synaptic function via adhesion molecules","call_identifier":"FWF","grant_number":"I03600","_id":"265CB4D0-B435-11E9-9278-68D0E5697425"}],"doi":"10.1038/s41467-021-23123-x","acknowledged_ssus":[{"_id":"PreCl"}],"language":[{"iso":"eng"}],"article_number":"3058","file_date_updated":"2021-05-28T12:39:43Z","ec_funded":1,"acknowledgement":"We thank A. Coll Manzano, F. Freeman, M. Ladron de Guevara, and A. Ç. Yahya for technical assistance, S. Deixler, A. Lepold, and A. Schlerka for the management of our animal colony, as well as M. Schunn and the Preclinical Facility team for technical assistance. We thank K. Heesom and her team at the University of Bristol Proteomics Facility for the proteomics sample preparation, data generation, and analysis support. We thank Y. B. Simon for kindly providing the plasmid for lentiviral labeling. Further, we thank M. Sixt for his advice regarding cell migration and the fruitful discussions. This work was supported by the ISTPlus postdoctoral fellowship (Grant Agreement No. 754411) to B.B., by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 (REVERSEAUTISM), and by the Austrian Science Fund (FWF) to G.N. (DK W1232-B24 and SFB F7807-B) and to J.G.D (I3600-B27).","year":"2021","publication_status":"published","publisher":"Springer Nature","department":[{"_id":"GaNo"},{"_id":"JoDa"},{"_id":"FlSc"},{"_id":"MiSi"},{"_id":"LifeSc"},{"_id":"Bio"}],"author":[{"first_name":"Jasmin","last_name":"Morandell","id":"4739D480-F248-11E8-B48F-1D18A9856A87","full_name":"Morandell, Jasmin"},{"full_name":"Schwarz, Lena A","first_name":"Lena A","last_name":"Schwarz","id":"29A8453C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Basilico, Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","orcid":"0000-0003-1843-3173","first_name":"Bernadette","last_name":"Basilico"},{"full_name":"Tasciyan, Saren","orcid":"0000-0003-1671-393X","id":"4323B49C-F248-11E8-B48F-1D18A9856A87","last_name":"Tasciyan","first_name":"Saren"},{"full_name":"Dimchev, Georgi A","last_name":"Dimchev","first_name":"Georgi A","orcid":"0000-0001-8370-6161","id":"38C393BE-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Nicolas","first_name":"Armel","id":"2A103192-F248-11E8-B48F-1D18A9856A87","full_name":"Nicolas, Armel"},{"first_name":"Christoph M","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M"},{"first_name":"Caroline","last_name":"Kreuzinger","id":"382077BA-F248-11E8-B48F-1D18A9856A87","full_name":"Kreuzinger, Caroline"},{"first_name":"Christoph","last_name":"Dotter","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9033-9096","full_name":"Dotter, Christoph"},{"full_name":"Knaus, Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","last_name":"Knaus","first_name":"Lisa"},{"full_name":"Dobler, Zoe","id":"D23090A2-9057-11EA-883A-A8396FC7A38F","last_name":"Dobler","first_name":"Zoe"},{"last_name":"Cacci","first_name":"Emanuele","full_name":"Cacci, Emanuele"},{"full_name":"Schur, Florian KM","first_name":"Florian KM","last_name":"Schur","id":"48AD8942-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4790-8078"},{"full_name":"Danzl, Johann G","first_name":"Johann G","last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973"},{"full_name":"Novarino, Gaia","first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178"}],"related_material":{"record":[{"id":"7800","status":"public","relation":"earlier_version"},{"id":"12401","status":"public","relation":"dissertation_contains"}],"link":[{"url":"https://ist.ac.at/en/news/defective-gene-slows-down-brain-cells/","relation":"press_release"}]},"date_updated":"2024-03-28T23:30:23Z","date_created":"2021-05-28T11:49:46Z","volume":12,"keyword":["General Biochemistry","Genetics and Molecular Biology"],"day":"24","has_accepted_license":"1","article_processing_charge":"No","publication":"Nature Communications","citation":{"short":"J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, G.A. Dimchev, A. Nicolas, C.M. Sommer, C. Kreuzinger, C. Dotter, L. Knaus, Z. Dobler, E. Cacci, F.K. Schur, J.G. Danzl, G. Novarino, Nature Communications 12 (2021).","mla":"Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” Nature Communications, vol. 12, no. 1, 3058, Springer Nature, 2021, doi:10.1038/s41467-021-23123-x.","chicago":"Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan, Georgi A Dimchev, Armel Nicolas, Christoph M Sommer, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” Nature Communications. Springer Nature, 2021. https://doi.org/10.1038/s41467-021-23123-x.","ama":"Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. 2021;12(1). doi:10.1038/s41467-021-23123-x","apa":"Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Dimchev, G. A., Nicolas, A., … Novarino, G. (2021). Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-021-23123-x","ieee":"J. Morandell et al., “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” Nature Communications, vol. 12, no. 1. Springer Nature, 2021.","ista":"Morandell J, Schwarz LA, Basilico B, Tasciyan S, Dimchev GA, Nicolas A, Sommer CM, Kreuzinger C, Dotter C, Knaus L, Dobler Z, Cacci E, Schur FK, Danzl JG, Novarino G. 2021. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. 12(1), 3058."},"article_type":"original","date_published":"2021-05-24T00:00:00Z","type":"journal_article","abstract":[{"lang":"eng","text":"De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 lead to autism spectrum disorder (ASD). In mouse, constitutive haploinsufficiency leads to motor coordination deficits as well as ASD-relevant social and cognitive impairments. However, induction of Cul3 haploinsufficiency later in life does not lead to ASD-relevant behaviors, pointing to an important role of Cul3 during a critical developmental window. Here we show that Cul3 is essential to regulate neuronal migration and, therefore, constitutive Cul3 heterozygous mutant mice display cortical lamination abnormalities. At the molecular level, we found that Cul3 controls neuronal migration by tightly regulating the amount of Plastin3 (Pls3), a previously unrecognized player of neural migration. Furthermore, we found that Pls3 cell-autonomously regulates cell migration by regulating actin cytoskeleton organization, and its levels are inversely proportional to neural migration speed. Finally, we provide evidence that cellular phenotypes associated with autism-linked gene haploinsufficiency can be rescued by transcriptional activation of the intact allele in vitro, offering a proof of concept for a potential therapeutic approach for ASDs."}],"issue":"1","_id":"9429","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","status":"public","ddc":["572"],"title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","intvolume":" 12","oa_version":"Published Version","file":[{"file_name":"2021_NatureCommunications_Morandell.pdf","access_level":"open_access","content_type":"application/pdf","file_size":9358599,"creator":"kschuh","relation":"main_file","file_id":"9430","date_created":"2021-05-28T12:39:43Z","date_updated":"2021-05-28T12:39:43Z","checksum":"337e0f7959c35ec959984cacdcb472ba","success":1}]},{"scopus_import":"1","article_processing_charge":"No","day":"01","page":"27-41","article_type":"original","citation":{"ama":"Jahr W, Velicky P, Danzl JG. Strategies to maximize performance in STimulated Emission Depletion (STED) nanoscopy of biological specimens. Methods. 2020;174(3):27-41. doi:10.1016/j.ymeth.2019.07.019","ieee":"W. Jahr, P. Velicky, and J. G. Danzl, “Strategies to maximize performance in STimulated Emission Depletion (STED) nanoscopy of biological specimens,” Methods, vol. 174, no. 3. Elsevier, pp. 27–41, 2020.","apa":"Jahr, W., Velicky, P., & Danzl, J. G. (2020). Strategies to maximize performance in STimulated Emission Depletion (STED) nanoscopy of biological specimens. Methods. Elsevier. https://doi.org/10.1016/j.ymeth.2019.07.019","ista":"Jahr W, Velicky P, Danzl JG. 2020. Strategies to maximize performance in STimulated Emission Depletion (STED) nanoscopy of biological specimens. Methods. 174(3), 27–41.","short":"W. Jahr, P. Velicky, J.G. Danzl, Methods 174 (2020) 27–41.","mla":"Jahr, Wiebke, et al. “Strategies to Maximize Performance in STimulated Emission Depletion (STED) Nanoscopy of Biological Specimens.” Methods, vol. 174, no. 3, Elsevier, 2020, pp. 27–41, doi:10.1016/j.ymeth.2019.07.019.","chicago":"Jahr, Wiebke, Philipp Velicky, and Johann G Danzl. “Strategies to Maximize Performance in STimulated Emission Depletion (STED) Nanoscopy of Biological Specimens.” Methods. Elsevier, 2020. https://doi.org/10.1016/j.ymeth.2019.07.019."},"publication":"Methods","date_published":"2020-03-01T00:00:00Z","type":"journal_article","issue":"3","abstract":[{"lang":"eng","text":"Super-resolution fluorescence microscopy has become an important catalyst for discovery in the life sciences. In STimulated Emission Depletion (STED) microscopy, a pattern of light drives fluorophores from a signal-emitting on-state to a non-signalling off-state. Only emitters residing in a sub-diffraction volume around an intensity minimum are allowed to fluoresce, rendering them distinguishable from the nearby, but dark fluorophores. STED routinely achieves resolution in the few tens of nanometers range in biological samples and is suitable for live imaging. Here, we review the working principle of STED and provide general guidelines for successful STED imaging. The strive for ever higher resolution comes at the cost of increased light burden. We discuss techniques to reduce light exposure and mitigate its detrimental effects on the specimen. These include specialized illumination strategies as well as protecting fluorophores from photobleaching mediated by high-intensity STED light. This opens up the prospect of volumetric imaging in living cells and tissues with diffraction-unlimited resolution in all three spatial dimensions."}],"intvolume":" 174","title":"Strategies to maximize performance in STimulated Emission Depletion (STED) nanoscopy of biological specimens","status":"public","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"6808","oa_version":"Submitted Version","publication_identifier":{"issn":["1046-2023"]},"month":"03","project":[{"call_identifier":"FWF","name":"Optical control of synaptic function via adhesion molecules","grant_number":"I03600","_id":"265CB4D0-B435-11E9-9278-68D0E5697425"},{"_id":"2668BFA0-B435-11E9-9278-68D0E5697425","grant_number":"LT00057","name":"High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration"}],"quality_controlled":"1","isi":1,"oa":1,"main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100895/"}],"external_id":{"pmid":["31344404"],"isi":["000525860400005"]},"language":[{"iso":"eng"}],"doi":"10.1016/j.ymeth.2019.07.019","publisher":"Elsevier","department":[{"_id":"JoDa"}],"publication_status":"published","pmid":1,"year":"2020","volume":174,"date_created":"2019-08-12T16:36:32Z","date_updated":"2023-08-17T13:59:57Z","author":[{"full_name":"Jahr, Wiebke","first_name":"Wiebke","last_name":"Jahr","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Velicky, Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2340-7431","first_name":"Philipp","last_name":"Velicky"},{"full_name":"Danzl, Johann G","first_name":"Johann G","last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973"}]},{"scopus_import":"1","day":"19","has_accepted_license":"1","article_processing_charge":"Yes (via OA deal)","publication":"Frontiers in Cellular Neuroscience","citation":{"ama":"Eguchi K, Velicky P, Saeckl E, et al. Advantages of acute brain slices prepared at physiological temperature in the characterization of synaptic functions. Frontiers in Cellular Neuroscience. 2020;14. doi:10.3389/fncel.2020.00063","apa":"Eguchi, K., Velicky, P., Saeckl, E., Itakura, M., Fukazawa, Y., Danzl, J. G., & Shigemoto, R. (2020). Advantages of acute brain slices prepared at physiological temperature in the characterization of synaptic functions. Frontiers in Cellular Neuroscience. Frontiers Media. https://doi.org/10.3389/fncel.2020.00063","ieee":"K. Eguchi et al., “Advantages of acute brain slices prepared at physiological temperature in the characterization of synaptic functions,” Frontiers in Cellular Neuroscience, vol. 14. Frontiers Media, 2020.","ista":"Eguchi K, Velicky P, Saeckl E, Itakura M, Fukazawa Y, Danzl JG, Shigemoto R. 2020. Advantages of acute brain slices prepared at physiological temperature in the characterization of synaptic functions. Frontiers in Cellular Neuroscience. 14, 63.","short":"K. Eguchi, P. Velicky, E. Saeckl, M. Itakura, Y. Fukazawa, J.G. Danzl, R. Shigemoto, Frontiers in Cellular Neuroscience 14 (2020).","mla":"Eguchi, Kohgaku, et al. “Advantages of Acute Brain Slices Prepared at Physiological Temperature in the Characterization of Synaptic Functions.” Frontiers in Cellular Neuroscience, vol. 14, 63, Frontiers Media, 2020, doi:10.3389/fncel.2020.00063.","chicago":"Eguchi, Kohgaku, Philipp Velicky, Elena Saeckl, Makoto Itakura, Yugo Fukazawa, Johann G Danzl, and Ryuichi Shigemoto. “Advantages of Acute Brain Slices Prepared at Physiological Temperature in the Characterization of Synaptic Functions.” Frontiers in Cellular Neuroscience. Frontiers Media, 2020. https://doi.org/10.3389/fncel.2020.00063."},"article_type":"original","date_published":"2020-03-19T00:00:00Z","type":"journal_article","abstract":[{"text":"Acute brain slice preparation is a powerful experimental model for investigating the characteristics of synaptic function in the brain. Although brain tissue is usually cut at ice-cold temperature (CT) to facilitate slicing and avoid neuronal damage, exposure to CT causes molecular and architectural changes of synapses. To address these issues, we investigated ultrastructural and electrophysiological features of synapses in mouse acute cerebellar slices prepared at ice-cold and physiological temperature (PT). In the slices prepared at CT, we found significant spine loss and reconstruction, synaptic vesicle rearrangement and decrease in synaptic proteins, all of which were not detected in slices prepared at PT. Consistent with these structural findings, slices prepared at PT showed higher release probability. Furthermore, preparation at PT allows electrophysiological recording immediately after slicing resulting in higher detectability of long-term depression (LTD) after motor learning compared with that at CT. These results indicate substantial advantages of the slice preparation at PT for investigating synaptic functions in different physiological conditions.","lang":"eng"}],"_id":"7665","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","ddc":["570"],"status":"public","title":"Advantages of acute brain slices prepared at physiological temperature in the characterization of synaptic functions","intvolume":" 14","file":[{"file_name":"2020_FrontiersCellularNeurosc_Eguchi.pdf","access_level":"open_access","creator":"dernst","content_type":"application/pdf","file_size":9227283,"file_id":"7668","relation":"main_file","date_created":"2020-04-20T10:59:49Z","date_updated":"2020-07-14T12:48:01Z","checksum":"1c145123c6f8dc3e2e4bd5a66a1ad60e"}],"oa_version":"Published Version","month":"03","publication_identifier":{"issn":["16625102"]},"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000525582200001"]},"quality_controlled":"1","isi":1,"project":[{"grant_number":"793482","_id":"2659CC84-B435-11E9-9278-68D0E5697425","name":"Ultrastructural analysis of phosphoinositides in nerve terminals: distribution, dynamics and physiological roles in synaptic transmission","call_identifier":"H2020"},{"call_identifier":"H2020","name":"In situ analysis of single channel subunit composition in neurons: physiological implication in synaptic plasticity and behaviour","grant_number":"694539","_id":"25CA28EA-B435-11E9-9278-68D0E5697425"},{"grant_number":"I03600","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Optical control of synaptic function via adhesion molecules"},{"name":"IST Austria Open Access 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Yugo"},{"id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","first_name":"Johann G","last_name":"Danzl","full_name":"Danzl, Johann G"},{"id":"499F3ABC-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8761-9444","first_name":"Ryuichi","last_name":"Shigemoto","full_name":"Shigemoto, Ryuichi"}],"date_created":"2020-04-19T22:00:55Z","date_updated":"2023-08-21T06:12:48Z","volume":14},{"month":"01","oa":1,"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"project":[{"grant_number":"I03600","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Optical control of synaptic function via adhesion molecules"},{"call_identifier":"FWF","name":"Molecular Drug Targets","grant_number":"W1232-B24","_id":"2548AE96-B435-11E9-9278-68D0E5697425"}],"doi":"10.1101/2020.01.10.902064 ","acknowledged_ssus":[{"_id":"PreCl"}],"language":[{"iso":"eng"}],"file_date_updated":"2020-07-14T12:48:03Z","year":"2020","publication_status":"submitted","department":[{"_id":"JoDa"},{"_id":"GaNo"},{"_id":"LifeSc"}],"publisher":"Cold Spring Harbor Laboratory","author":[{"last_name":"Morandell","first_name":"Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","full_name":"Morandell, Jasmin"},{"full_name":"Schwarz, Lena A","id":"29A8453C-F248-11E8-B48F-1D18A9856A87","last_name":"Schwarz","first_name":"Lena A"},{"full_name":"Basilico, Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","orcid":"0000-0003-1843-3173","first_name":"Bernadette","last_name":"Basilico"},{"full_name":"Tasciyan, Saren","last_name":"Tasciyan","first_name":"Saren","orcid":"0000-0003-1671-393X","id":"4323B49C-F248-11E8-B48F-1D18A9856A87"},{"id":"2A103192-F248-11E8-B48F-1D18A9856A87","first_name":"Armel","last_name":"Nicolas","full_name":"Nicolas, Armel"},{"orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","last_name":"Sommer","first_name":"Christoph M","full_name":"Sommer, Christoph M"},{"full_name":"Kreuzinger, Caroline","id":"382077BA-F248-11E8-B48F-1D18A9856A87","first_name":"Caroline","last_name":"Kreuzinger"},{"id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","last_name":"Knaus","first_name":"Lisa","full_name":"Knaus, Lisa"},{"id":"D23090A2-9057-11EA-883A-A8396FC7A38F","first_name":"Zoe","last_name":"Dobler","full_name":"Dobler, Zoe"},{"first_name":"Emanuele","last_name":"Cacci","full_name":"Cacci, Emanuele"},{"full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","last_name":"Danzl","first_name":"Johann G"},{"full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino"}],"related_material":{"record":[{"id":"9429","status":"public","relation":"later_version"},{"id":"8620","relation":"dissertation_contains","status":"public"}]},"date_created":"2020-05-05T14:31:33Z","date_updated":"2024-03-28T23:30:14Z","day":"11","article_processing_charge":"No","has_accepted_license":"1","publication":"bioRxiv","citation":{"chicago":"Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan, Armel Nicolas, Christoph M Sommer, Caroline Kreuzinger, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2020.01.10.902064 .","short":"J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, A. Nicolas, C.M. Sommer, C. Kreuzinger, L. Knaus, Z. Dobler, E. Cacci, J.G. Danzl, G. Novarino, BioRxiv (n.d.).","mla":"Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2020.01.10.902064 .","ieee":"J. Morandell et al., “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” bioRxiv. Cold Spring Harbor Laboratory.","apa":"Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Nicolas, A., Sommer, C. M., … Novarino, G. (n.d.). Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.01.10.902064 ","ista":"Morandell J, Schwarz LA, Basilico B, Tasciyan S, Nicolas A, Sommer CM, Kreuzinger C, Knaus L, Dobler Z, Cacci E, Danzl JG, Novarino G. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. bioRxiv, 10.1101/2020.01.10.902064 .","ama":"Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. bioRxiv. doi:10.1101/2020.01.10.902064 "},"date_published":"2020-01-11T00:00:00Z","type":"preprint","abstract":[{"text":"De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 (CUL3) lead to autism spectrum disorder (ASD). Here, we used Cul3 mouse models to evaluate the consequences of Cul3 mutations in vivo. Our results show that Cul3 haploinsufficient mice exhibit deficits in motor coordination as well as ASD-relevant social and cognitive impairments. Cul3 mutant brain displays cortical lamination abnormalities due to defective neuronal migration and reduced numbers of excitatory and inhibitory neurons. In line with the observed abnormal columnar organization, Cul3 haploinsufficiency is associated with decreased spontaneous excitatory and inhibitory activity in the cortex. At the molecular level, employing a quantitative proteomic approach, we show that Cul3 regulates cytoskeletal and adhesion protein abundance in mouse embryos. Abnormal regulation of cytoskeletal proteins in Cul3 mutant neuronal cells results in atypical organization of the actin mesh at the cell leading edge, likely causing the observed migration deficits. In contrast to these important functions early in development, Cul3 deficiency appears less relevant at adult stages. In fact, induction of Cul3 haploinsufficiency in adult mice does not result in the behavioral defects observed in constitutive Cul3 haploinsufficient animals. Taken together, our data indicate that Cul3 has a critical role in the regulation of cytoskeletal proteins and neuronal migration and that ASD-associated defects and behavioral abnormalities are primarily due to Cul3 functions at early developmental stages.","lang":"eng"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"7800","status":"public","title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","ddc":["570"],"oa_version":"Preprint","file":[{"file_id":"7801","relation":"main_file","checksum":"c6799ab5daba80efe8e2ed63c15f8c81","date_updated":"2020-07-14T12:48:03Z","date_created":"2020-05-05T14:31:19Z","access_level":"open_access","file_name":"2020.01.10.902064v1.full.pdf","creator":"rsix","file_size":2931370,"content_type":"application/pdf"}]}]