[{"type":"journal_article","date_updated":"2023-10-31T12:17:20Z","_id":"14443","publisher":"American Medical Association","doi":"10.1001/jamapsychiatry.2023.2996","article_processing_charge":"No","quality_controlled":"1","page":"1066-1074","external_id":{"pmid":["37610741"]},"year":"2023","date_published":"2023-10-01T00:00:00Z","pmid":1,"status":"public","publication":"JAMA Psychiatry","article_type":"review","date_created":"2023-10-22T22:01:14Z","volume":80,"oa_version":"None","title":"Addressing global environmental challenges to mental health using population neuroscience: A review","author":[{"last_name":"Schumann","full_name":"Schumann, Gunter","first_name":"Gunter"},{"last_name":"Andreassen","full_name":"Andreassen, Ole A.","first_name":"Ole A."},{"first_name":"Tobias","full_name":"Banaschewski, Tobias","last_name":"Banaschewski"},{"first_name":"Vince D.","last_name":"Calhoun","full_name":"Calhoun, Vince D."},{"full_name":"Clinton, Nicholas","last_name":"Clinton","first_name":"Nicholas"},{"first_name":"Sylvane","last_name":"Desrivieres","full_name":"Desrivieres, Sylvane"},{"first_name":"Ragnhild Eek","full_name":"Brandlistuen, Ragnhild Eek","last_name":"Brandlistuen"},{"first_name":"Jianfeng","last_name":"Feng","full_name":"Feng, Jianfeng"},{"first_name":"Soeren","last_name":"Hese","full_name":"Hese, Soeren"},{"first_name":"Esther","last_name":"Hitchen","full_name":"Hitchen, Esther"},{"first_name":"Per","last_name":"Hoffmann","full_name":"Hoffmann, Per"},{"full_name":"Jia, Tianye","last_name":"Jia","first_name":"Tianye"},{"full_name":"Jirsa, Viktor","last_name":"Jirsa","first_name":"Viktor"},{"first_name":"Andre F.","last_name":"Marquand","full_name":"Marquand, Andre F."},{"first_name":"Frauke","last_name":"Nees","full_name":"Nees, Frauke"},{"last_name":"Nöthen","full_name":"Nöthen, Markus M.","first_name":"Markus M."},{"first_name":"Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino","full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Elli","last_name":"Polemiti","full_name":"Polemiti, Elli"},{"first_name":"Markus","last_name":"Ralser","full_name":"Ralser, Markus"},{"first_name":"Michael","full_name":"Rapp, Michael","last_name":"Rapp"},{"full_name":"Schepanski, Kerstin","last_name":"Schepanski","first_name":"Kerstin"},{"full_name":"Schikowski, Tamara","last_name":"Schikowski","first_name":"Tamara"},{"full_name":"Slater, Mel","last_name":"Slater","first_name":"Mel"},{"last_name":"Sommer","full_name":"Sommer, Peter","first_name":"Peter"},{"full_name":"Stahl, Bernd Carsten","last_name":"Stahl","first_name":"Bernd Carsten"},{"first_name":"Paul M.","last_name":"Thompson","full_name":"Thompson, Paul M."},{"first_name":"Sven","last_name":"Twardziok","full_name":"Twardziok, Sven"},{"first_name":"Dennis","last_name":"Van Der Meer","full_name":"Van Der Meer, Dennis"},{"first_name":"Henrik","last_name":"Walter","full_name":"Walter, Henrik"},{"full_name":"Westlye, Lars","last_name":"Westlye","first_name":"Lars"}],"day":"01","scopus_import":"1","publication_identifier":{"eissn":["2168-6238"]},"publication_status":"published","intvolume":"        80","abstract":[{"lang":"eng","text":"Importance  Climate change, pollution, urbanization, socioeconomic inequality, and psychosocial effects of the COVID-19 pandemic have caused massive changes in environmental conditions that affect brain health during the life span, both on a population level as well as on the level of the individual. How these environmental factors influence the brain, behavior, and mental illness is not well known.\r\nObservations  A research strategy enabling population neuroscience to contribute to identify brain mechanisms underlying environment-related mental illness by leveraging innovative enrichment tools for data federation, geospatial observation, climate and pollution measures, digital health, and novel data integration techniques is described. This strategy can inform innovative treatments that target causal cognitive and molecular mechanisms of mental illness related to the environment. An example is presented of the environMENTAL Project that is leveraging federated cohort data of over 1.5 million European citizens and patients enriched with deep phenotyping data from large-scale behavioral neuroimaging cohorts to identify brain mechanisms related to environmental adversity underlying symptoms of depression, anxiety, stress, and substance misuse.\r\nConclusions and Relevance  This research will lead to the development of objective biomarkers and evidence-based interventions that will significantly improve outcomes of environment-related mental illness."}],"department":[{"_id":"GaNo"}],"month":"10","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","issue":"10","citation":{"ista":"Schumann G, Andreassen OA, Banaschewski T, Calhoun VD, Clinton N, Desrivieres S, Brandlistuen RE, Feng J, Hese S, Hitchen E, Hoffmann P, Jia T, Jirsa V, Marquand AF, Nees F, Nöthen MM, Novarino G, Polemiti E, Ralser M, Rapp M, Schepanski K, Schikowski T, Slater M, Sommer P, Stahl BC, Thompson PM, Twardziok S, Van Der Meer D, Walter H, Westlye L. 2023. Addressing global environmental challenges to mental health using population neuroscience: A review. JAMA Psychiatry. 80(10), 1066–1074.","chicago":"Schumann, Gunter, Ole A. Andreassen, Tobias Banaschewski, Vince D. Calhoun, Nicholas Clinton, Sylvane Desrivieres, Ragnhild Eek Brandlistuen, et al. “Addressing Global Environmental Challenges to Mental Health Using Population Neuroscience: A Review.” <i>JAMA Psychiatry</i>. American Medical Association, 2023. <a href=\"https://doi.org/10.1001/jamapsychiatry.2023.2996\">https://doi.org/10.1001/jamapsychiatry.2023.2996</a>.","apa":"Schumann, G., Andreassen, O. A., Banaschewski, T., Calhoun, V. D., Clinton, N., Desrivieres, S., … Westlye, L. (2023). Addressing global environmental challenges to mental health using population neuroscience: A review. <i>JAMA Psychiatry</i>. American Medical Association. <a href=\"https://doi.org/10.1001/jamapsychiatry.2023.2996\">https://doi.org/10.1001/jamapsychiatry.2023.2996</a>","mla":"Schumann, Gunter, et al. “Addressing Global Environmental Challenges to Mental Health Using Population Neuroscience: A Review.” <i>JAMA Psychiatry</i>, vol. 80, no. 10, American Medical Association, 2023, pp. 1066–74, doi:<a href=\"https://doi.org/10.1001/jamapsychiatry.2023.2996\">10.1001/jamapsychiatry.2023.2996</a>.","ama":"Schumann G, Andreassen OA, Banaschewski T, et al. Addressing global environmental challenges to mental health using population neuroscience: A review. <i>JAMA Psychiatry</i>. 2023;80(10):1066-1074. doi:<a href=\"https://doi.org/10.1001/jamapsychiatry.2023.2996\">10.1001/jamapsychiatry.2023.2996</a>","ieee":"G. Schumann <i>et al.</i>, “Addressing global environmental challenges to mental health using population neuroscience: A review,” <i>JAMA Psychiatry</i>, vol. 80, no. 10. American Medical Association, pp. 1066–1074, 2023.","short":"G. Schumann, O.A. Andreassen, T. Banaschewski, V.D. Calhoun, N. Clinton, S. Desrivieres, R.E. Brandlistuen, J. Feng, S. Hese, E. Hitchen, P. Hoffmann, T. Jia, V. Jirsa, A.F. Marquand, F. Nees, M.M. Nöthen, G. Novarino, E. Polemiti, M. Ralser, M. Rapp, K. Schepanski, T. Schikowski, M. Slater, P. Sommer, B.C. Stahl, P.M. Thompson, S. Twardziok, D. Van Der Meer, H. Walter, L. Westlye, JAMA Psychiatry 80 (2023) 1066–1074."},"language":[{"iso":"eng"}]},{"department":[{"_id":"GaNo"}],"file":[{"content_type":"application/pdf","access_level":"open_access","file_name":"2023_FrontiersPsychiatry_Narzisi.pdf","success":1,"checksum":"0a76373e9a4c0fc199f80380de257e86","relation":"main_file","date_updated":"2023-10-30T12:48:40Z","creator":"dernst","date_created":"2023-10-30T12:48:40Z","file_size":147878,"file_id":"14468"}],"article_number":"1287879","month":"10","citation":{"ama":"Narzisi A, Halladay A, Masi G, Novarino G, Lord C. Tempering expectations: Considerations on the current state of stem cells therapy for autism treatment. <i>Frontiers in Psychiatry</i>. 2023;14. doi:<a href=\"https://doi.org/10.3389/fpsyt.2023.1287879\">10.3389/fpsyt.2023.1287879</a>","ieee":"A. Narzisi, A. Halladay, G. Masi, G. Novarino, and C. Lord, “Tempering expectations: Considerations on the current state of stem cells therapy for autism treatment,” <i>Frontiers in Psychiatry</i>, vol. 14. Frontiers, 2023.","short":"A. Narzisi, A. Halladay, G. Masi, G. Novarino, C. Lord, Frontiers in Psychiatry 14 (2023).","ista":"Narzisi A, Halladay A, Masi G, Novarino G, Lord C. 2023. Tempering expectations: Considerations on the current state of stem cells therapy for autism treatment. Frontiers in Psychiatry. 14, 1287879.","chicago":"Narzisi, Antonio, Alycia Halladay, Gabriele Masi, Gaia Novarino, and Catherine Lord. “Tempering Expectations: Considerations on the Current State of Stem Cells Therapy for Autism Treatment.” <i>Frontiers in Psychiatry</i>. Frontiers, 2023. <a href=\"https://doi.org/10.3389/fpsyt.2023.1287879\">https://doi.org/10.3389/fpsyt.2023.1287879</a>.","apa":"Narzisi, A., Halladay, A., Masi, G., Novarino, G., &#38; Lord, C. (2023). Tempering expectations: Considerations on the current state of stem cells therapy for autism treatment. <i>Frontiers in Psychiatry</i>. Frontiers. <a href=\"https://doi.org/10.3389/fpsyt.2023.1287879\">https://doi.org/10.3389/fpsyt.2023.1287879</a>","mla":"Narzisi, Antonio, et al. “Tempering Expectations: Considerations on the Current State of Stem Cells Therapy for Autism Treatment.” <i>Frontiers in Psychiatry</i>, vol. 14, 1287879, Frontiers, 2023, doi:<a href=\"https://doi.org/10.3389/fpsyt.2023.1287879\">10.3389/fpsyt.2023.1287879</a>."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa":1,"language":[{"iso":"eng"}],"volume":14,"article_type":"letter_note","date_created":"2023-10-29T23:01:16Z","author":[{"first_name":"Antonio","full_name":"Narzisi, Antonio","last_name":"Narzisi"},{"first_name":"Alycia","last_name":"Halladay","full_name":"Halladay, Alycia"},{"last_name":"Masi","full_name":"Masi, Gabriele","first_name":"Gabriele"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia","last_name":"Novarino","orcid":"0000-0002-7673-7178","first_name":"Gaia"},{"first_name":"Catherine","last_name":"Lord","full_name":"Lord, Catherine"}],"scopus_import":"1","day":"03","oa_version":"Published Version","title":"Tempering expectations: Considerations on the current state of stem cells therapy for autism treatment","publication_status":"published","publication_identifier":{"eissn":["1664-0640"]},"file_date_updated":"2023-10-30T12:48:40Z","has_accepted_license":"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","image":"/images/cc_by.png","short":"CC BY (4.0)"},"intvolume":"        14","year":"2023","isi":1,"external_id":{"isi":["001084841700001"],"pmid":["37854442"]},"pmid":1,"date_published":"2023-10-03T00:00:00Z","acknowledgement":"The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work has been partially supported by Italian Ministry of Health Grant RC2023 (and the 5 × 1,000 voluntary contributions). The authors thank the children and their families with whom they work daily.","publication":"Frontiers in Psychiatry","status":"public","date_updated":"2023-12-13T13:06:07Z","_id":"14455","type":"journal_article","doi":"10.3389/fpsyt.2023.1287879","article_processing_charge":"Yes","publisher":"Frontiers","quality_controlled":"1","ddc":["570"]},{"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"mla":"Xu, Jiayuan, et al. “Effects of Urban Living Environments on Mental Health in Adults.” <i>Nature Medicine</i>, vol. 29, Springer Nature, 2023, pp. 1456–67, doi:<a href=\"https://doi.org/10.1038/s41591-023-02365-w\">10.1038/s41591-023-02365-w</a>.","apa":"Xu, J., Liu, N., Polemiti, E., Garcia-Mondragon, L., Tang, J., Liu, X., … Ogoh, G. (2023). Effects of urban living environments on mental health in adults. <i>Nature Medicine</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41591-023-02365-w\">https://doi.org/10.1038/s41591-023-02365-w</a>","ista":"Xu J, Liu N, Polemiti E, Garcia-Mondragon L, Tang J, Liu X, Lett T, Yu L, Nöthen MM, Feng J, Yu C, Marquand A, Schumann G, Walter H, Heinz A, Ralser M, Twardziok S, Vaidya N, Serin E, Jentsch M, Hitchen E, Eils R, Taron UH, Schütz T, Schepanski K, Banks J, Banaschewski T, Jansone K, Christmann N, Meyer-Lindenberg A, Tost H, Holz N, Schwarz E, Stringaris A, Neidhart M, Nees F, Siehl S, A. Andreassen O, T. Westlye L, Van Der Meer D, Fernandez S, Kjelkenes R, Ask H, Rapp M, Tschorn M, Böttger SJ, Novarino G, Marr L, Slater M, Viapiana GF, Orosa FE, Gallego J, Pastor A, Forstner A, Hoffmann P, M. Nöthen M, J. Forstner A, Claus I, Miller A, Heilmann-Heimbach S, Sommer P, Boye M, Wilbertz J, Schmitt K, Jirsa V, Petkoski S, Pitel S, Otten L, Athanasiadis AP, Pearmund C, Spanlang B, Alvarez E, Sanchez M, Giner A, Hese S, Renner P, Jia T, Gong Y, Xia Y, Chang X, Calhoun V, Liu J, Thompson P, Clinton N, Desrivieres S, H. Young A, Stahl B, Ogoh G. 2023. Effects of urban living environments on mental health in adults. Nature Medicine. 29, 1456–1467.","chicago":"Xu, Jiayuan, Nana Liu, Elli Polemiti, Liliana Garcia-Mondragon, Jie Tang, Xiaoxuan Liu, Tristram Lett, et al. “Effects of Urban Living Environments on Mental Health in Adults.” <i>Nature Medicine</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1038/s41591-023-02365-w\">https://doi.org/10.1038/s41591-023-02365-w</a>.","short":"J. Xu, N. Liu, E. Polemiti, L. Garcia-Mondragon, J. Tang, X. Liu, T. Lett, L. Yu, M.M. Nöthen, J. Feng, C. Yu, A. Marquand, G. Schumann, H. Walter, A. Heinz, M. Ralser, S. Twardziok, N. Vaidya, E. Serin, M. Jentsch, E. Hitchen, R. Eils, U.H. Taron, T. Schütz, K. Schepanski, J. Banks, T. Banaschewski, K. Jansone, N. Christmann, A. Meyer-Lindenberg, H. Tost, N. Holz, E. Schwarz, A. Stringaris, M. Neidhart, F. Nees, S. Siehl, O. A. Andreassen, L. T. Westlye, D. Van Der Meer, S. Fernandez, R. Kjelkenes, H. Ask, M. Rapp, M. Tschorn, S.J. Böttger, G. Novarino, L. Marr, M. Slater, G.F. Viapiana, F.E. Orosa, J. Gallego, A. Pastor, A. Forstner, P. Hoffmann, M. M. Nöthen, A. J. Forstner, I. Claus, A. Miller, S. Heilmann-Heimbach, P. Sommer, M. Boye, J. Wilbertz, K. Schmitt, V. Jirsa, S. Petkoski, S. Pitel, L. Otten, A.P. Athanasiadis, C. Pearmund, B. Spanlang, E. Alvarez, M. Sanchez, A. Giner, S. Hese, P. Renner, T. Jia, Y. Gong, Y. Xia, X. Chang, V. Calhoun, J. Liu, P. Thompson, N. Clinton, S. Desrivieres, A. H. Young, B. Stahl, G. Ogoh, Nature Medicine 29 (2023) 1456–1467.","ieee":"J. Xu <i>et al.</i>, “Effects of urban living environments on mental health in adults,” <i>Nature Medicine</i>, vol. 29. Springer Nature, pp. 1456–1467, 2023.","ama":"Xu J, Liu N, Polemiti E, et al. Effects of urban living environments on mental health in adults. <i>Nature Medicine</i>. 2023;29:1456-1467. doi:<a href=\"https://doi.org/10.1038/s41591-023-02365-w\">10.1038/s41591-023-02365-w</a>"},"language":[{"iso":"eng"}],"oa":1,"file":[{"file_id":"13171","date_updated":"2023-06-26T10:15:44Z","creator":"dernst","file_size":7365360,"date_created":"2023-06-26T10:15:44Z","checksum":"bcd3225b2731c3442fa98987fd3bd46d","relation":"main_file","access_level":"open_access","content_type":"application/pdf","success":1,"file_name":"2023_NatureMedicine_Xu.pdf"}],"department":[{"_id":"GaNo"}],"month":"06","file_date_updated":"2023-06-26T10:15:44Z","publication_identifier":{"issn":["1078-8956"],"eissn":["1546-170X"]},"publication_status":"published","abstract":[{"text":"Urban-living individuals are exposed to many environmental factors that may combine and interact to influence mental health. While individual factors of an urban environment have been investigated in isolation, no attempt has been made to model how complex, real-life exposure to living in the city relates to brain and mental health, and how this is moderated by genetic factors. Using the data of 156,075 participants from the UK Biobank, we carried out sparse canonical correlation analyses to investigate the relationships between urban environments and psychiatric symptoms. We found an environmental profile of social deprivation, air pollution, street network and urban land-use density that was positively correlated with an affective symptom group (r = 0.22, Pperm < 0.001), mediated by brain volume differences consistent with reward processing, and moderated by genes enriched for stress response, including CRHR1, explaining 2.01% of the variance in brain volume differences. Protective factors such as greenness and generous destination accessibility were negatively correlated with an anxiety symptom group (r = 0.10, Pperm < 0.001), mediated by brain regions necessary for emotion regulation and moderated by EXD3, explaining 1.65% of the variance. The third urban environmental profile was correlated with an emotional instability symptom group (r = 0.03, Pperm < 0.001). Our findings suggest that different environmental profiles of urban living may influence specific psychiatric symptom groups through distinct neurobiological pathways.","lang":"eng"}],"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","image":"/images/cc_by.png","short":"CC BY (4.0)"},"intvolume":"        29","has_accepted_license":"1","date_created":"2023-06-25T22:00:46Z","article_type":"original","volume":29,"title":"Effects of urban living environments on mental health in adults","oa_version":"Published Version","scopus_import":"1","day":"15","author":[{"full_name":"Xu, Jiayuan","last_name":"Xu","first_name":"Jiayuan"},{"first_name":"Nana","last_name":"Liu","full_name":"Liu, Nana"},{"first_name":"Elli","full_name":"Polemiti, Elli","last_name":"Polemiti"},{"last_name":"Garcia-Mondragon","full_name":"Garcia-Mondragon, Liliana","first_name":"Liliana"},{"last_name":"Tang","full_name":"Tang, Jie","first_name":"Jie"},{"first_name":"Xiaoxuan","last_name":"Liu","full_name":"Liu, Xiaoxuan"},{"last_name":"Lett","full_name":"Lett, Tristram","first_name":"Tristram"},{"first_name":"Le","full_name":"Yu, Le","last_name":"Yu"},{"first_name":"Markus M.","full_name":"Nöthen, Markus M.","last_name":"Nöthen"},{"first_name":"Jianfeng","full_name":"Feng, Jianfeng","last_name":"Feng"},{"last_name":"Yu","full_name":"Yu, Chunshui","first_name":"Chunshui"},{"last_name":"Marquand","full_name":"Marquand, Andre","first_name":"Andre"},{"first_name":"Gunter","last_name":"Schumann","full_name":"Schumann, Gunter"},{"full_name":"Walter, Henrik","last_name":"Walter","first_name":"Henrik"},{"first_name":"Andreas","full_name":"Heinz, Andreas","last_name":"Heinz"},{"first_name":"Markus","full_name":"Ralser, Markus","last_name":"Ralser"},{"first_name":"Sven","full_name":"Twardziok, Sven","last_name":"Twardziok"},{"last_name":"Vaidya","full_name":"Vaidya, Nilakshi","first_name":"Nilakshi"},{"first_name":"Emin","full_name":"Serin, Emin","last_name":"Serin"},{"last_name":"Jentsch","full_name":"Jentsch, Marcel","first_name":"Marcel"},{"first_name":"Esther","full_name":"Hitchen, Esther","last_name":"Hitchen"},{"last_name":"Eils","full_name":"Eils, Roland","first_name":"Roland"},{"first_name":"Ulrike Helene","last_name":"Taron","full_name":"Taron, Ulrike Helene"},{"last_name":"Schütz","full_name":"Schütz, Tatjana","first_name":"Tatjana"},{"last_name":"Schepanski","full_name":"Schepanski, Kerstin","first_name":"Kerstin"},{"last_name":"Banks","full_name":"Banks, Jamie","first_name":"Jamie"},{"first_name":"Tobias","full_name":"Banaschewski, Tobias","last_name":"Banaschewski"},{"last_name":"Jansone","full_name":"Jansone, Karina","first_name":"Karina"},{"full_name":"Christmann, Nina","last_name":"Christmann","first_name":"Nina"},{"last_name":"Meyer-Lindenberg","full_name":"Meyer-Lindenberg, Andreas","first_name":"Andreas"},{"full_name":"Tost, Heike","last_name":"Tost","first_name":"Heike"},{"first_name":"Nathalie","full_name":"Holz, Nathalie","last_name":"Holz"},{"full_name":"Schwarz, Emanuel","last_name":"Schwarz","first_name":"Emanuel"},{"full_name":"Stringaris, Argyris","last_name":"Stringaris","first_name":"Argyris"},{"full_name":"Neidhart, Maja","last_name":"Neidhart","first_name":"Maja"},{"first_name":"Frauke","full_name":"Nees, Frauke","last_name":"Nees"},{"first_name":"Sebastian","last_name":"Siehl","full_name":"Siehl, Sebastian"},{"last_name":"A. Andreassen","full_name":"A. Andreassen, Ole","first_name":"Ole"},{"full_name":"T. Westlye, Lars","last_name":"T. Westlye","first_name":"Lars"},{"full_name":"Van Der Meer, Dennis","last_name":"Van Der Meer","first_name":"Dennis"},{"full_name":"Fernandez, Sara","last_name":"Fernandez","first_name":"Sara"},{"last_name":"Kjelkenes","full_name":"Kjelkenes, Rikka","first_name":"Rikka"},{"last_name":"Ask","full_name":"Ask, Helga","first_name":"Helga"},{"last_name":"Rapp","full_name":"Rapp, Michael","first_name":"Michael"},{"first_name":"Mira","last_name":"Tschorn","full_name":"Tschorn, Mira"},{"first_name":"Sarah Jane","last_name":"Böttger","full_name":"Böttger, Sarah Jane"},{"last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","first_name":"Gaia"},{"first_name":"Lena","last_name":"Marr","id":"4406F586-F248-11E8-B48F-1D18A9856A87","full_name":"Marr, Lena"},{"last_name":"Slater","full_name":"Slater, Mel","first_name":"Mel"},{"full_name":"Viapiana, Guillem Feixas","last_name":"Viapiana","first_name":"Guillem Feixas"},{"first_name":"Francisco Eiroa","full_name":"Orosa, Francisco Eiroa","last_name":"Orosa"},{"first_name":"Jaime","full_name":"Gallego, Jaime","last_name":"Gallego"},{"first_name":"Alvaro","last_name":"Pastor","full_name":"Pastor, Alvaro"},{"first_name":"Andreas","full_name":"Forstner, Andreas","last_name":"Forstner"},{"first_name":"Per","full_name":"Hoffmann, Per","last_name":"Hoffmann"},{"last_name":"M. Nöthen","full_name":"M. Nöthen, Markus","first_name":"Markus"},{"last_name":"J. Forstner","full_name":"J. Forstner, Andreas","first_name":"Andreas"},{"first_name":"Isabelle","last_name":"Claus","full_name":"Claus, Isabelle"},{"first_name":"Abbi","last_name":"Miller","full_name":"Miller, Abbi"},{"first_name":"Stefanie","last_name":"Heilmann-Heimbach","full_name":"Heilmann-Heimbach, Stefanie"},{"last_name":"Sommer","full_name":"Sommer, Peter","first_name":"Peter"},{"full_name":"Boye, Mona","last_name":"Boye","first_name":"Mona"},{"first_name":"Johannes","last_name":"Wilbertz","full_name":"Wilbertz, Johannes"},{"first_name":"Karen","last_name":"Schmitt","full_name":"Schmitt, Karen"},{"full_name":"Jirsa, Viktor","last_name":"Jirsa","first_name":"Viktor"},{"first_name":"Spase","full_name":"Petkoski, Spase","last_name":"Petkoski"},{"first_name":"Séverine","full_name":"Pitel, Séverine","last_name":"Pitel"},{"full_name":"Otten, Lisa","last_name":"Otten","first_name":"Lisa"},{"full_name":"Athanasiadis, Anastasios Polykarpos","last_name":"Athanasiadis","first_name":"Anastasios Polykarpos"},{"last_name":"Pearmund","full_name":"Pearmund, Charlie","first_name":"Charlie"},{"first_name":"Bernhard","last_name":"Spanlang","full_name":"Spanlang, Bernhard"},{"full_name":"Alvarez, Elena","last_name":"Alvarez","first_name":"Elena"},{"last_name":"Sanchez","full_name":"Sanchez, Mavi","first_name":"Mavi"},{"full_name":"Giner, Arantxa","last_name":"Giner","first_name":"Arantxa"},{"first_name":"Sören","full_name":"Hese, Sören","last_name":"Hese"},{"first_name":"Paul","full_name":"Renner, Paul","last_name":"Renner"},{"first_name":"Tianye","last_name":"Jia","full_name":"Jia, Tianye"},{"full_name":"Gong, Yanting","last_name":"Gong","first_name":"Yanting"},{"first_name":"Yunman","last_name":"Xia","full_name":"Xia, Yunman"},{"first_name":"Xiao","full_name":"Chang, Xiao","last_name":"Chang"},{"last_name":"Calhoun","full_name":"Calhoun, Vince","first_name":"Vince"},{"full_name":"Liu, Jingyu","last_name":"Liu","first_name":"Jingyu"},{"last_name":"Thompson","full_name":"Thompson, Paul","first_name":"Paul"},{"full_name":"Clinton, Nicholas","last_name":"Clinton","first_name":"Nicholas"},{"first_name":"Sylvane","last_name":"Desrivieres","full_name":"Desrivieres, Sylvane"},{"first_name":"Allan","last_name":"H. Young","full_name":"H. Young, Allan"},{"first_name":"Bernd","full_name":"Stahl, Bernd","last_name":"Stahl"},{"last_name":"Ogoh","full_name":"Ogoh, George","first_name":"George"}],"acknowledgement":"This work received support from the European Union-funded Horizon Europe project ‘environMENTAL’ (no. 101057429 to G.S., A.M. and M.M.N.) and cofunding by UK Research and Innovation under the UK Government’s Horizon Europe funding guarantee (nos. 10041392 and 10038599) for study design and data analysis; the Horizon 2020-funded European Research Council Advanced Grant ‘STRATIFY’ (no. 695313 to G.S. for study design and data analysis); the Human Brain Project (HBP SGA3, no. 945539 to G.S. for study design and data analysis); the National Institutes of Health (grant no. R01DA049238 to G.S. for study design and data analysis); the German Research Foundation (COPE; grant no. 675346 to G.S. for study design and data analysis); the National Natural Science Foundation of China (grant no. 82001797 to J.X., grant no. 82030053 to C.Y., grant no. 82202093 to J.T. and grant no. 82150710554 to G.S. for study design, data analysis and preparation of the manuscript); National Key Research and Development Program of China (grant no. 2018YFC1314301 to C.Y. for study design and data analysis); Tianjin Applied Basic Research Diversified Investment Foundation (grant no. 21JCYBJC01360 to J.X. for study design and data analysis); Tianjin Health Technology Project (grant no. TJWJ2021QN002 to J.X. for preparation of the manuscript); Science & Technology Development Fund of the Tianjin Education Commission for Higher Education (grant no. 2019KJ195 to J.X. for preparation of the manuscript); the Tianjin Medical University ‘Clinical Talent Training 123 Climbing Plan’ to J.X. for the preparation of the manuscript; Tianjin Key Medical Discipline (Specialty) Construction Project (grant no. TJYXZDXK-001A to C.Y. for preparation of the manuscript); the National Key R&D Program of China (grant no. 2022YFE0209400 to L.Y. for study design and data analysis); the Tsinghua University Initiative Scientific Research Program (grant no. 2021Z11GHX002 to L.Y. for study design and data analysis); the National Key Scientific and Technological Infrastructure Project ‘Earth System Science Numerical Simulator Facility’ (EarthLab to L.Y. for study design and data analysis); the Chinese National High-end Foreign Expert Recruitment Plan to G.S.; and the Alexander von Humboldt Foundation to G.S. for study design and data analysis.","date_published":"2023-06-15T00:00:00Z","publication":"Nature Medicine","status":"public","external_id":{"isi":["001013172700001"]},"year":"2023","isi":1,"quality_controlled":"1","ddc":["570"],"page":"1456-1467","type":"journal_article","_id":"13168","date_updated":"2023-12-13T11:25:55Z","publisher":"Springer Nature","article_processing_charge":"No","doi":"10.1038/s41591-023-02365-w"},{"date_published":"2023-08-01T00:00:00Z","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.).","ec_funded":1,"pmid":1,"status":"public","publication":"Nature Methods","project":[{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","name":"Optical control of synaptic function via adhesion molecules","grant_number":"I03600","call_identifier":"FWF"},{"grant_number":"W1232-B24","name":"Molecular Drug Targets","call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"The Wittgenstein Prize","grant_number":"Z00312","call_identifier":"FWF"},{"_id":"23889792-32DE-11EA-91FC-C7463DDC885E","name":"High content imaging to decode human immune cell interactions in health and allergic disease"},{"grant_number":"665385","name":"International IST Doctoral Program","call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"},{"_id":"24F9549A-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and Modeling","grant_number":"715767"},{"_id":"25444568-B435-11E9-9278-68D0E5697425","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","grant_number":"715508","call_identifier":"H2020"},{"call_identifier":"H2020","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","call_identifier":"H2020","name":"Synaptic computations of the hippocampal CA3 circuitry","grant_number":"101026635"},{"_id":"2668BFA0-B435-11E9-9278-68D0E5697425","name":"High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration","grant_number":"LT00057"}],"related_material":{"link":[{"relation":"software","url":"https://github.com/danzllab/LIONESS"}],"record":[{"relation":"research_data","status":"public","id":"12817"},{"status":"public","relation":"shorter_version","id":"14770"}]},"external_id":{"pmid":["37429995"],"isi":["001025621500001"]},"year":"2023","isi":1,"quality_controlled":"1","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1038/s41592-023-01936-6"}],"page":"1256-1265","type":"journal_article","_id":"13267","date_updated":"2024-01-10T08:37:48Z","publisher":"Springer Nature","article_processing_charge":"Yes","doi":"10.1038/s41592-023-01936-6","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"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. <i>Nature Methods</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41592-023-01936-6\">https://doi.org/10.1038/s41592-023-01936-6</a>","mla":"Velicky, Philipp, et al. “Dense 4D Nanoscale Reconstruction of Living Brain Tissue.” <i>Nature Methods</i>, vol. 20, Springer Nature, 2023, pp. 1256–65, doi:<a href=\"https://doi.org/10.1038/s41592-023-01936-6\">10.1038/s41592-023-01936-6</a>.","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.","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.” <i>Nature Methods</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1038/s41592-023-01936-6\">https://doi.org/10.1038/s41592-023-01936-6</a>.","ieee":"P. Velicky <i>et al.</i>, “Dense 4D nanoscale reconstruction of living brain tissue,” <i>Nature Methods</i>, vol. 20. Springer Nature, pp. 1256–1265, 2023.","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.","ama":"Velicky P, Miguel Villalba E, Michalska JM, et al. Dense 4D nanoscale reconstruction of living brain tissue. <i>Nature Methods</i>. 2023;20:1256-1265. doi:<a href=\"https://doi.org/10.1038/s41592-023-01936-6\">10.1038/s41592-023-01936-6</a>"},"language":[{"iso":"eng"}],"oa":1,"department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"},{"_id":"Bio"}],"month":"08","publication_identifier":{"eissn":["1548-7105"],"issn":["1548-7091"]},"publication_status":"published","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"E-Lib"},{"_id":"LifeSc"},{"_id":"M-Shop"}],"intvolume":"        20","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."}],"date_created":"2023-07-23T22:01:13Z","article_type":"original","volume":20,"oa_version":"Published Version","title":"Dense 4D nanoscale reconstruction of living brain tissue","scopus_import":"1","day":"01","author":[{"first_name":"Philipp","orcid":"0000-0002-2340-7431","full_name":"Velicky, Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","last_name":"Velicky"},{"id":"3FB91342-F248-11E8-B48F-1D18A9856A87","full_name":"Miguel Villalba, Eder","last_name":"Miguel Villalba","first_name":"Eder","orcid":"0000-0001-5665-0430"},{"id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","full_name":"Michalska, Julia M","last_name":"Michalska","orcid":"0000-0003-3862-1235","first_name":"Julia M"},{"last_name":"Lyudchik","full_name":"Lyudchik, Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","first_name":"Julia"},{"first_name":"Donglai","last_name":"Wei","full_name":"Wei, Donglai"},{"full_name":"Lin, Zudi","last_name":"Lin","first_name":"Zudi"},{"orcid":"0000-0002-8698-3823","first_name":"Jake","last_name":"Watson","id":"63836096-4690-11EA-BD4E-32803DDC885E","full_name":"Watson, Jake"},{"full_name":"Troidl, Jakob","last_name":"Troidl","first_name":"Jakob"},{"last_name":"Beyer","full_name":"Beyer, Johanna","first_name":"Johanna"},{"last_name":"Ben Simon","id":"43DF3136-F248-11E8-B48F-1D18A9856A87","full_name":"Ben Simon, Yoav","first_name":"Yoav"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M","last_name":"Sommer","first_name":"Christoph M","orcid":"0000-0003-1216-9105"},{"last_name":"Jahr","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","full_name":"Jahr, Wiebke","first_name":"Wiebke"},{"last_name":"Cenameri","full_name":"Cenameri, Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886","first_name":"Alban"},{"first_name":"Johannes","last_name":"Broichhagen","full_name":"Broichhagen, Johannes"},{"last_name":"Grant","full_name":"Grant, Seth G.N.","first_name":"Seth G.N."},{"first_name":"Peter M","orcid":"0000-0001-5001-4804","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas"},{"first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia","last_name":"Novarino"},{"last_name":"Pfister","full_name":"Pfister, Hanspeter","first_name":"Hanspeter"},{"id":"49876194-F248-11E8-B48F-1D18A9856A87","full_name":"Bickel, Bernd","last_name":"Bickel","orcid":"0000-0001-6511-9385","first_name":"Bernd"},{"full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","last_name":"Danzl","orcid":"0000-0001-8559-3973","first_name":"Johann G"}]},{"main_file_link":[{"url":"https://doi.org/10.1038/s41587-023-01911-8","open_access":"1"}],"quality_controlled":"1","doi":"10.1038/s41587-023-01911-8","article_processing_charge":"Yes (in subscription journal)","publisher":"Springer Nature","date_updated":"2024-02-21T12:18:18Z","_id":"14257","type":"journal_article","project":[{"grant_number":"I03600","name":"Optical control of synaptic function via adhesion molecules","call_identifier":"FWF","_id":"265CB4D0-B435-11E9-9278-68D0E5697425"},{"_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Molecular Drug Targets","grant_number":"W1232-B24"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"The Wittgenstein Prize","grant_number":"Z00312"},{"_id":"23889792-32DE-11EA-91FC-C7463DDC885E","name":"High content imaging to decode human immune cell interactions in health and allergic disease"},{"grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425"},{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","call_identifier":"H2020"},{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"International IST Doctoral Program","grant_number":"665385"},{"grant_number":"101026635","name":"Synaptic computations of the hippocampal CA3 circuitry","call_identifier":"H2020","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9"}],"publication":"Nature Biotechnology","status":"public","ec_funded":1,"date_published":"2023-08-31T00:00:00Z","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.).","isi":1,"year":"2023","external_id":{"isi":["001065254200001"]},"related_material":{"link":[{"relation":"software","url":"https://github.com/danzllab/CATS"}],"record":[{"id":"13126","relation":"research_data","status":"public"}]},"abstract":[{"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.","lang":"eng"}],"acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"publication_identifier":{"eissn":["1546-1696"],"issn":["1087-0156"]},"publication_status":"epub_ahead","author":[{"first_name":"Julia M","orcid":"0000-0003-3862-1235","last_name":"Michalska","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","full_name":"Michalska, Julia M"},{"first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","full_name":"Lyudchik, Julia","last_name":"Lyudchik"},{"orcid":"0000-0002-2340-7431","first_name":"Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","full_name":"Velicky, Philipp","last_name":"Velicky"},{"first_name":"Hana","last_name":"Korinkova","full_name":"Korinkova, Hana","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed"},{"first_name":"Jake","orcid":"0000-0002-8698-3823","last_name":"Watson","full_name":"Watson, Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E"},{"id":"9ac8f577-2357-11eb-997a-e566c5550886","full_name":"Cenameri, Alban","last_name":"Cenameri","first_name":"Alban"},{"orcid":"0000-0003-1216-9105","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M","last_name":"Sommer"},{"first_name":"Nicole","orcid":"0000-0002-3183-8207","full_name":"Amberg, Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","last_name":"Amberg"},{"first_name":"Alessandro","orcid":"0000-0003-2356-9403","last_name":"Venturino","full_name":"Venturino, Alessandro","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Karl","full_name":"Roessler, Karl","last_name":"Roessler"},{"first_name":"Thomas","full_name":"Czech, Thomas","last_name":"Czech"},{"first_name":"Romana","last_name":"Höftberger","full_name":"Höftberger, Romana"},{"id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","full_name":"Siegert, Sandra","last_name":"Siegert","orcid":"0000-0001-8635-0877","first_name":"Sandra"},{"full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","orcid":"0000-0002-7673-7178","first_name":"Gaia"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","last_name":"Jonas","orcid":"0000-0001-5001-4804","first_name":"Peter M"},{"last_name":"Danzl","full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G","orcid":"0000-0001-8559-3973"}],"day":"31","scopus_import":"1","title":"Imaging brain tissue architecture across millimeter to nanometer scales","oa_version":"Published Version","article_type":"original","date_created":"2023-09-03T22:01:15Z","oa":1,"language":[{"iso":"eng"}],"citation":{"mla":"Michalska, Julia M., et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” <i>Nature Biotechnology</i>, Springer Nature, 2023, doi:<a href=\"https://doi.org/10.1038/s41587-023-01911-8\">10.1038/s41587-023-01911-8</a>.","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. <i>Nature Biotechnology</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41587-023-01911-8\">https://doi.org/10.1038/s41587-023-01911-8</a>","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.","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.” <i>Nature Biotechnology</i>. Springer Nature, 2023. <a href=\"https://doi.org/10.1038/s41587-023-01911-8\">https://doi.org/10.1038/s41587-023-01911-8</a>.","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).","ieee":"J. M. Michalska <i>et al.</i>, “Imaging brain tissue architecture across millimeter to nanometer scales,” <i>Nature Biotechnology</i>. Springer Nature, 2023.","ama":"Michalska JM, Lyudchik J, Velicky P, et al. Imaging brain tissue architecture across millimeter to nanometer scales. <i>Nature Biotechnology</i>. 2023. doi:<a href=\"https://doi.org/10.1038/s41587-023-01911-8\">10.1038/s41587-023-01911-8</a>"},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"08","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"},{"_id":"Bio"},{"_id":"RySh"}]},{"ec_funded":1,"acknowledgement":"We thank A. Freeman and V. Voronin for technical assistance, S. Deixler, A. Stichelberger, M. Schunn, and the Preclinical Facility for managing our animal colony. We thank L. Andersen and J. Sonntag, who were involved in generating the MADM lines. We thank the ISTA LSF Mass Spectrometry Core Facility for assistance with the proteomic analysis, as well as the ISTA electron microscopy and Imaging and Optics facility for technical support. Metabolomics LC-MS/MS analysis was performed by the Metabolomics Facility at Vienna BioCenter Core Facilities (VBCF). We acknowledge the support of the EMBL Metabolomics Core Facility (MCF) for lipidomics and intracellular metabolomics mass spectrometry data acquisition and analysis. RNA sequencing was performed by the Next Generation Sequencing Facility at VBCF. Schematics were generated using Biorender.com. This work was supported by the Austrian Science Fund (FWF, DK W1232-B24) and by the European Union’s Horizon 2020 research and innovation program (ERC) grant 725780 (LinPro) to S.H. and 715508 (REVERSEAUTISM) to G.N.","date_published":"2023-04-27T00:00:00Z","status":"public","publication":"Cell","project":[{"_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Molecular Drug Targets","grant_number":"W1232-B24"},{"call_identifier":"H2020","grant_number":"725780","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","_id":"260018B0-B435-11E9-9278-68D0E5697425"},{"_id":"25444568-B435-11E9-9278-68D0E5697425","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","grant_number":"715508","call_identifier":"H2020"}],"keyword":["General Biochemistry","Genetics and Molecular Biology"],"isi":1,"year":"2023","related_material":{"link":[{"url":"https://ista.ac.at/en/news/feed-them-or-lose-them/","description":"News on ISTA Website","relation":"press_release"}],"record":[{"status":"public","relation":"dissertation_contains","id":"13107"}]},"external_id":{"isi":["000991468700001"]},"quality_controlled":"1","page":"1950-1967.e25","ddc":["570"],"_id":"12802","date_updated":"2024-02-07T08:03:32Z","type":"journal_article","article_processing_charge":"Yes (via OA deal)","doi":"10.1016/j.cell.2023.02.037","publisher":"Elsevier","citation":{"ista":"Knaus L, Basilico B, Malzl D, Gerykova Bujalkova M, Smogavec M, Schwarz LA, Gorkiewicz S, Amberg N, Pauler F, Knittl-Frank C, Tassinari M, Maulide N, Rülicke T, Menche J, Hippenmeyer S, Novarino G. 2023. Large neutral amino acid levels tune perinatal neuronal excitability and survival. Cell. 186(9), 1950–1967.e25.","chicago":"Knaus, Lisa, Bernadette Basilico, Daniel Malzl, Maria Gerykova Bujalkova, Mateja Smogavec, Lena A. Schwarz, Sarah Gorkiewicz, et al. “Large Neutral Amino Acid Levels Tune Perinatal Neuronal Excitability and Survival.” <i>Cell</i>. Elsevier, 2023. <a href=\"https://doi.org/10.1016/j.cell.2023.02.037\">https://doi.org/10.1016/j.cell.2023.02.037</a>.","apa":"Knaus, L., Basilico, B., Malzl, D., Gerykova Bujalkova, M., Smogavec, M., Schwarz, L. A., … Novarino, G. (2023). Large neutral amino acid levels tune perinatal neuronal excitability and survival. <i>Cell</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.cell.2023.02.037\">https://doi.org/10.1016/j.cell.2023.02.037</a>","mla":"Knaus, Lisa, et al. “Large Neutral Amino Acid Levels Tune Perinatal Neuronal Excitability and Survival.” <i>Cell</i>, vol. 186, no. 9, Elsevier, 2023, p. 1950–1967.e25, doi:<a href=\"https://doi.org/10.1016/j.cell.2023.02.037\">10.1016/j.cell.2023.02.037</a>.","ama":"Knaus L, Basilico B, Malzl D, et al. Large neutral amino acid levels tune perinatal neuronal excitability and survival. <i>Cell</i>. 2023;186(9):1950-1967.e25. doi:<a href=\"https://doi.org/10.1016/j.cell.2023.02.037\">10.1016/j.cell.2023.02.037</a>","ieee":"L. Knaus <i>et al.</i>, “Large neutral amino acid levels tune perinatal neuronal excitability and survival,” <i>Cell</i>, vol. 186, no. 9. Elsevier, p. 1950–1967.e25, 2023.","short":"L. Knaus, B. Basilico, D. Malzl, M. Gerykova Bujalkova, M. Smogavec, L.A. Schwarz, S. Gorkiewicz, N. Amberg, F. Pauler, C. Knittl-Frank, M. Tassinari, N. Maulide, T. Rülicke, J. Menche, S. Hippenmeyer, G. Novarino, Cell 186 (2023) 1950–1967.e25."},"issue":"9","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa":1,"language":[{"iso":"eng"}],"department":[{"_id":"SiHi"},{"_id":"GaNo"}],"file":[{"file_id":"12889","date_created":"2023-05-02T09:26:21Z","file_size":15712841,"date_updated":"2023-05-02T09:26:21Z","creator":"dernst","relation":"main_file","checksum":"47e94fbe19e86505b429cb7a5b503ce6","success":1,"file_name":"2023_Cell_Knaus.pdf","access_level":"open_access","content_type":"application/pdf"}],"month":"04","file_date_updated":"2023-05-02T09:26:21Z","publication_identifier":{"issn":["0092-8674"]},"publication_status":"published","has_accepted_license":"1","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"EM-Fac"},{"_id":"Bio"},{"_id":"LifeSc"}],"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","image":"/images/cc_by.png","short":"CC BY (4.0)"},"abstract":[{"lang":"eng","text":"Little is known about the critical metabolic changes that neural cells have to undergo during development and how temporary shifts in this program can influence brain circuitries and behavior. Inspired by the discovery that mutations in SLC7A5, a transporter of metabolically essential large neutral amino acids (LNAAs), lead to autism, we employed metabolomic profiling to study the metabolic states of the cerebral cortex across different developmental stages. We found that the forebrain undergoes significant metabolic remodeling throughout development, with certain groups of metabolites showing stage-specific changes, but what are the consequences of perturbing this metabolic program? By manipulating Slc7a5 expression in neural cells, we found that the metabolism of LNAAs and lipids are interconnected in the cortex. Deletion of Slc7a5 in neurons affects the postnatal metabolic state, leading to a shift in lipid metabolism. Additionally, it causes stage- and cell-type-specific alterations in neuronal activity patterns, resulting in a long-term circuit dysfunction."}],"intvolume":"       186","volume":186,"date_created":"2023-04-05T08:15:40Z","article_type":"original","scopus_import":"1","day":"27","author":[{"full_name":"Knaus, Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","last_name":"Knaus","first_name":"Lisa"},{"orcid":"0000-0003-1843-3173","first_name":"Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","full_name":"Basilico, Bernadette","last_name":"Basilico"},{"first_name":"Daniel","last_name":"Malzl","full_name":"Malzl, Daniel"},{"full_name":"Gerykova Bujalkova, Maria","last_name":"Gerykova Bujalkova","first_name":"Maria"},{"full_name":"Smogavec, Mateja","last_name":"Smogavec","first_name":"Mateja"},{"first_name":"Lena A.","full_name":"Schwarz, Lena A.","last_name":"Schwarz"},{"first_name":"Sarah","last_name":"Gorkiewicz","full_name":"Gorkiewicz, Sarah","id":"f141a35d-15a9-11ec-9fb2-fef6becc7b6f"},{"last_name":"Amberg","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","full_name":"Amberg, Nicole","first_name":"Nicole","orcid":"0000-0002-3183-8207"},{"first_name":"Florian","orcid":"0000-0002-7462-0048","last_name":"Pauler","full_name":"Pauler, Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Knittl-Frank","full_name":"Knittl-Frank, Christian","first_name":"Christian"},{"last_name":"Tassinari","full_name":"Tassinari, Marianna","id":"7af593f1-d44a-11ed-bf94-a3646a6bb35e","first_name":"Marianna"},{"last_name":"Maulide","full_name":"Maulide, Nuno","first_name":"Nuno"},{"last_name":"Rülicke","full_name":"Rülicke, Thomas","first_name":"Thomas"},{"first_name":"Jörg","last_name":"Menche","full_name":"Menche, Jörg"},{"orcid":"0000-0003-2279-1061","first_name":"Simon","last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia"}],"title":"Large neutral amino acid levels tune perinatal neuronal excitability and survival","oa_version":"Published Version"},{"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"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","image":"/images/cc_by.png","short":"CC BY (4.0)"},"intvolume":"        39","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"}],"has_accepted_license":"1","file_date_updated":"2022-04-15T09:06:25Z","publication_identifier":{"issn":["2211-1247"]},"publication_status":"published","oa_version":"Published Version","title":"CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories","day":"05","author":[{"first_name":"Carlo Emanuele","last_name":"Villa","full_name":"Villa, Carlo Emanuele"},{"first_name":"Cristina","last_name":"Cheroni","full_name":"Cheroni, Cristina"},{"first_name":"Christoph","orcid":"0000-0002-9033-9096","last_name":"Dotter","full_name":"Dotter, Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Alejandro","last_name":"López-Tóbon","full_name":"López-Tóbon, Alejandro"},{"last_name":"Oliveira","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","full_name":"Oliveira, Bárbara","first_name":"Bárbara"},{"first_name":"Roberto","id":"42C9F57E-F248-11E8-B48F-1D18A9856A87","full_name":"Sacco, Roberto","last_name":"Sacco"},{"last_name":"Yahya","id":"365A65F8-F248-11E8-B48F-1D18A9856A87","full_name":"Yahya, Aysan Çerağ","first_name":"Aysan Çerağ"},{"first_name":"Jasmin","full_name":"Morandell, Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","last_name":"Morandell"},{"first_name":"Michele","last_name":"Gabriele","full_name":"Gabriele, Michele"},{"last_name":"Tavakoli","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","full_name":"Tavakoli, Mojtaba","orcid":"0000-0002-7667-6854","first_name":"Mojtaba"},{"first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","full_name":"Lyudchik, Julia","last_name":"Lyudchik"},{"last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","first_name":"Christoph M"},{"last_name":"Gabitto","full_name":"Gabitto, Mariano","first_name":"Mariano"},{"last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G","first_name":"Johann G","orcid":"0000-0001-8559-3973"},{"first_name":"Giuseppe","full_name":"Testa, Giuseppe","last_name":"Testa"},{"orcid":"0000-0002-7673-7178","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia","last_name":"Novarino"}],"date_created":"2022-04-15T09:03:10Z","article_type":"original","volume":39,"language":[{"iso":"eng"}],"oa":1,"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"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).","ieee":"C. E. Villa <i>et al.</i>, “CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories,” <i>Cell Reports</i>, vol. 39, no. 1. Elsevier, 2022.","ama":"Villa CE, Cheroni C, Dotter C, et al. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. <i>Cell Reports</i>. 2022;39(1). doi:<a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">10.1016/j.celrep.2022.110615</a>","mla":"Villa, Carlo Emanuele, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” <i>Cell Reports</i>, vol. 39, no. 1, 110615, Elsevier, 2022, doi:<a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">10.1016/j.celrep.2022.110615</a>.","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. <i>Cell Reports</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">https://doi.org/10.1016/j.celrep.2022.110615</a>","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.","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.” <i>Cell Reports</i>. Elsevier, 2022. <a href=\"https://doi.org/10.1016/j.celrep.2022.110615\">https://doi.org/10.1016/j.celrep.2022.110615</a>."},"issue":"1","month":"04","article_number":"110615","file":[{"file_size":"7808644","date_created":"2022-04-15T09:06:25Z","creator":"dernst","date_updated":"2022-04-15T09:06:25Z","file_id":"11164","success":1,"file_name":"2022_CellReports_Villa.pdf","access_level":"open_access","content_type":"application/pdf","relation":"main_file","checksum":"b4e8d68f0268dec499af333e6fd5d8e1"}],"department":[{"_id":"JoDa"},{"_id":"GaNo"}],"ddc":["570"],"quality_controlled":"1","publisher":"Elsevier","article_processing_charge":"Yes","doi":"10.1016/j.celrep.2022.110615","type":"journal_article","_id":"11160","date_updated":"2024-03-25T23:30:25Z","status":"public","publication":"Cell Reports","project":[{"call_identifier":"H2020","grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","_id":"25444568-B435-11E9-9278-68D0E5697425"},{"_id":"2690FEAC-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Identification of converging Molecular Pathways Across Chromatinopathies as Targets for Therapy","grant_number":"I04205"}],"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.","date_published":"2022-04-05T00:00:00Z","ec_funded":1,"pmid":1,"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"12364"}]},"external_id":{"pmid":["35385734"],"isi":["000785983900003"]},"year":"2022","isi":1,"keyword":["General Biochemistry","Genetics and Molecular Biology"]},{"author":[{"last_name":"Velicky","full_name":"Velicky, Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2340-7431","first_name":"Philipp"},{"orcid":"0000-0001-5665-0430","first_name":"Eder","id":"3FB91342-F248-11E8-B48F-1D18A9856A87","full_name":"Miguel Villalba, Eder","last_name":"Miguel Villalba"},{"last_name":"Michalska","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","full_name":"Michalska, Julia M","orcid":"0000-0003-3862-1235","first_name":"Julia M"},{"first_name":"Donglai","full_name":"Wei, Donglai","last_name":"Wei"},{"first_name":"Zudi","last_name":"Lin","full_name":"Lin, Zudi"},{"last_name":"Watson","full_name":"Watson, Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E","orcid":"0000-0002-8698-3823","first_name":"Jake"},{"full_name":"Troidl, Jakob","last_name":"Troidl","first_name":"Jakob"},{"last_name":"Beyer","full_name":"Beyer, Johanna","first_name":"Johanna"},{"id":"43DF3136-F248-11E8-B48F-1D18A9856A87","full_name":"Ben Simon, Yoav","last_name":"Ben Simon","first_name":"Yoav"},{"last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M","first_name":"Christoph M","orcid":"0000-0003-1216-9105"},{"first_name":"Wiebke","last_name":"Jahr","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","full_name":"Jahr, Wiebke"},{"full_name":"Cenameri, Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886","last_name":"Cenameri","first_name":"Alban"},{"last_name":"Broichhagen","full_name":"Broichhagen, Johannes","first_name":"Johannes"},{"first_name":"Seth G. N.","full_name":"Grant, Seth G. N.","last_name":"Grant"},{"first_name":"Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas","full_name":"Jonas, Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia","first_name":"Gaia","orcid":"0000-0002-7673-7178"},{"last_name":"Pfister","full_name":"Pfister, Hanspeter","first_name":"Hanspeter"},{"orcid":"0000-0001-6511-9385","first_name":"Bernd","full_name":"Bickel, Bernd","id":"49876194-F248-11E8-B48F-1D18A9856A87","last_name":"Bickel"},{"full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","last_name":"Danzl","orcid":"0000-0001-8559-3973","first_name":"Johann G"}],"doi":"10.1101/2022.03.16.484431","day":"09","article_processing_charge":"No","oa_version":"Preprint","publisher":"Cold Spring Harbor Laboratory","title":"Saturated reconstruction of living brain tissue","date_updated":"2024-03-25T23:30:11Z","_id":"11943","type":"preprint","date_created":"2022-08-23T11:07:59Z","abstract":[{"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 <jats:italic>in-silico</jats:italic> reconstruction<jats:sup>1–5</jats:sup>, yet is limited to fixed specimens and static representations. Light microscopy allows live observation, with super-resolution approaches<jats:sup>6–12</jats:sup> 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) microscopy<jats:sup>6,13</jats:sup> in extracellularly labelled tissue<jats:sup>14</jats:sup> 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.","lang":"eng"}],"main_file_link":[{"url":"https://doi.org/10.1101/2022.03.16.484431","open_access":"1"}],"publication_status":"submitted","year":"2022","related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"12470"}]},"month":"05","department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"}],"oa":1,"language":[{"iso":"eng"}],"publication":"bioRxiv","status":"public","citation":{"ieee":"P. Velicky <i>et al.</i>, “Saturated reconstruction of living brain tissue,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory.","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.).","ama":"Velicky P, Miguel Villalba E, Michalska JM, et al. Saturated reconstruction of living brain tissue. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2022.03.16.484431\">10.1101/2022.03.16.484431</a>","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. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2022.03.16.484431\">https://doi.org/10.1101/2022.03.16.484431</a>","mla":"Velicky, Philipp, et al. “Saturated Reconstruction of Living Brain Tissue.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, doi:<a href=\"https://doi.org/10.1101/2022.03.16.484431\">10.1101/2022.03.16.484431</a>.","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.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href=\"https://doi.org/10.1101/2022.03.16.484431\">https://doi.org/10.1101/2022.03.16.484431</a>.","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, <a href=\"https://doi.org/10.1101/2022.03.16.484431\">10.1101/2022.03.16.484431</a>."},"date_published":"2022-05-09T00:00:00Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"},{"oa_version":"Preprint","title":"Uncovering brain tissue architecture across scales with super-resolution light microscopy","publisher":"Cold Spring Harbor Laboratory","day":"18","article_processing_charge":"No","author":[{"orcid":"0000-0003-3862-1235","first_name":"Julia M","full_name":"Michalska, Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","last_name":"Michalska"},{"first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","full_name":"Lyudchik, Julia","last_name":"Lyudchik"},{"first_name":"Philipp","orcid":"0000-0002-2340-7431","last_name":"Velicky","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","full_name":"Velicky, Philipp"},{"first_name":"Hana","full_name":"Korinkova, Hana","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","last_name":"Korinkova"},{"last_name":"Watson","id":"63836096-4690-11EA-BD4E-32803DDC885E","full_name":"Watson, Jake","first_name":"Jake","orcid":"0000-0002-8698-3823"},{"first_name":"Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886","full_name":"Cenameri, Alban","last_name":"Cenameri"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M","last_name":"Sommer","first_name":"Christoph M","orcid":"0000-0003-1216-9105"},{"full_name":"Venturino, Alessandro","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","last_name":"Venturino","orcid":"0000-0003-2356-9403","first_name":"Alessandro"},{"first_name":"Karl","last_name":"Roessler","full_name":"Roessler, Karl"},{"first_name":"Thomas","last_name":"Czech","full_name":"Czech, Thomas"},{"orcid":"0000-0001-8635-0877","first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","full_name":"Siegert, Sandra","last_name":"Siegert"},{"first_name":"Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino","full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0001-5001-4804","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","last_name":"Jonas"},{"last_name":"Danzl","full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G","orcid":"0000-0001-8559-3973"}],"doi":"10.1101/2022.08.17.504272","date_created":"2022-08-24T08:24:52Z","type":"preprint","_id":"11950","date_updated":"2024-03-25T23:30:11Z","abstract":[{"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.","lang":"eng"}],"publication_status":"submitted","main_file_link":[{"url":"https://doi.org/10.1101/2022.08.17.504272","open_access":"1"}],"month":"08","related_material":{"record":[{"id":"12470","relation":"dissertation_contains","status":"public"}]},"year":"2022","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"}],"publication":"bioRxiv","language":[{"iso":"eng"}],"status":"public","oa":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_published":"2022-08-18T00:00:00Z","citation":{"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. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2022.08.17.504272\">https://doi.org/10.1101/2022.08.17.504272</a>","mla":"Michalska, Julia M., et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, doi:<a href=\"https://doi.org/10.1101/2022.08.17.504272\">10.1101/2022.08.17.504272</a>.","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, <a href=\"https://doi.org/10.1101/2022.08.17.504272\">10.1101/2022.08.17.504272</a>.","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.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href=\"https://doi.org/10.1101/2022.08.17.504272\">https://doi.org/10.1101/2022.08.17.504272</a>.","ieee":"J. M. Michalska <i>et al.</i>, “Uncovering brain tissue architecture across scales with super-resolution light microscopy,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory.","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.).","ama":"Michalska JM, Lyudchik J, Velicky P, et al. Uncovering brain tissue architecture across scales with super-resolution light microscopy. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2022.08.17.504272\">10.1101/2022.08.17.504272</a>"}},{"citation":{"ista":"Guerrini R, Mei D, Szigeti MK, Pepe S, Koenig MK, Von Allmen G, Cho MT, McDonald K, Baker J, Bhambhani V, Powis Z, Rodan L, Nabbout R, Barcia G, Rosenfeld JA, Bacino CA, Mignot C, Power LH, Harris CJ, Marjanovic D, Møller RS, Hammer TB, Keski Filppula R, Vieira P, Hildebrandt C, Sacharow S, Maragliano L, Benfenati F, Lachlan K, Benneche A, Petit F, de Sainte Agathe JM, Hallinan B, Si Y, Wentzensen IM, Zou F, Narayanan V, Matsumoto N, Boncristiano A, la Marca G, Kato M, Anderson K, Barba C, Sturiale L, Garozzo D, Bei R, Masuelli L, Conti V, Novarino G, Fassio A. 2022. Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal homeostasis. Brain. 145(8), 2687–2703.","chicago":"Guerrini, Renzo, Davide Mei, Margit Katalin Szigeti, Sara Pepe, Mary Kay Koenig, Gretchen Von Allmen, Megan T Cho, et al. “Phenotypic and Genetic Spectrum of ATP6V1A Encephalopathy: A Disorder of Lysosomal Homeostasis.” <i>Brain</i>. Oxford University Press, 2022. <a href=\"https://doi.org/10.1093/brain/awac145\">https://doi.org/10.1093/brain/awac145</a>.","apa":"Guerrini, R., Mei, D., Szigeti, M. K., Pepe, S., Koenig, M. K., Von Allmen, G., … Fassio, A. (2022). Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal homeostasis. <i>Brain</i>. Oxford University Press. <a href=\"https://doi.org/10.1093/brain/awac145\">https://doi.org/10.1093/brain/awac145</a>","mla":"Guerrini, Renzo, et al. “Phenotypic and Genetic Spectrum of ATP6V1A Encephalopathy: A Disorder of Lysosomal Homeostasis.” <i>Brain</i>, vol. 145, no. 8, Oxford University Press, 2022, pp. 2687–703, doi:<a href=\"https://doi.org/10.1093/brain/awac145\">10.1093/brain/awac145</a>.","ama":"Guerrini R, Mei D, Szigeti MK, et al. Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal homeostasis. <i>Brain</i>. 2022;145(8):2687-2703. doi:<a href=\"https://doi.org/10.1093/brain/awac145\">10.1093/brain/awac145</a>","ieee":"R. Guerrini <i>et al.</i>, “Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal homeostasis,” <i>Brain</i>, vol. 145, no. 8. Oxford University Press, pp. 2687–2703, 2022.","short":"R. Guerrini, D. Mei, M.K. Szigeti, S. Pepe, M.K. Koenig, G. Von Allmen, M.T. Cho, K. McDonald, J. Baker, V. Bhambhani, Z. Powis, L. Rodan, R. Nabbout, G. Barcia, J.A. Rosenfeld, C.A. Bacino, C. Mignot, L.H. Power, C.J. Harris, D. Marjanovic, R.S. Møller, T.B. Hammer, R. Keski Filppula, P. Vieira, C. Hildebrandt, S. Sacharow, L. Maragliano, F. Benfenati, K. Lachlan, A. Benneche, F. Petit, J.M. de Sainte Agathe, B. Hallinan, Y. Si, I.M. Wentzensen, F. Zou, V. Narayanan, N. Matsumoto, A. Boncristiano, G. la Marca, M. Kato, K. Anderson, C. Barba, L. Sturiale, D. Garozzo, R. Bei, L. Masuelli, V. Conti, G. Novarino, A. Fassio, Brain 145 (2022) 2687–2703."},"issue":"8","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa":1,"language":[{"iso":"eng"}],"department":[{"_id":"GaNo"}],"month":"08","publication_status":"published","publication_identifier":{"issn":["0006-8950"],"eissn":["1460-2156"]},"acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"LifeSc"}],"abstract":[{"text":"Vacuolar-type H+-ATPase (V-ATPase) is a multimeric complex present in a variety of cellular membranes that acts as an ATP-dependent proton pump and plays a key role in pH homeostasis and intracellular signalling pathways. In humans, 22 autosomal genes encode for a redundant set of subunits allowing the composition of diverse V-ATPase complexes with specific properties and expression. Sixteen subunits have been linked to human disease.\r\nHere we describe 26 patients harbouring 20 distinct pathogenic de novo missense ATP6V1A variants, mainly clustering within the ATP synthase α/β family-nucleotide-binding domain. At a mean age of 7 years (extremes: 6 weeks, youngest deceased patient to 22 years, oldest patient) clinical pictures included early lethal encephalopathies with rapidly progressive massive brain atrophy, severe developmental epileptic encephalopathies and static intellectual disability with epilepsy. The first clinical manifestation was early hypotonia, in 70%; 81% developed epilepsy, manifested as developmental epileptic encephalopathies in 58% of the cohort and with infantile spasms in 62%; 63% of developmental epileptic encephalopathies failed to achieve any developmental, communicative or motor skills. Less severe outcomes were observed in 23% of patients who, at a mean age of 10 years and 6 months, exhibited moderate intellectual disability, with independent walking and variable epilepsy. None of the patients developed communicative language. Microcephaly (38%) and amelogenesis imperfecta/enamel dysplasia (42%) were additional clinical features. Brain MRI demonstrated hypomyelination and generalized atrophy in 68%. Atrophy was progressive in all eight individuals undergoing repeated MRIs.</jats:p>\r\n               <jats:p>Fibroblasts of two patients with developmental epileptic encephalopathies showed decreased LAMP1 expression, Lysotracker staining and increased organelle pH, consistent with lysosomal impairment and loss of V-ATPase function. Fibroblasts of two patients with milder disease, exhibited a different phenotype with increased Lysotracker staining, decreased organelle pH and no significant modification in LAMP1 expression. Quantification of substrates for lysosomal enzymes in cellular extracts from four patients revealed discrete accumulation. Transmission electron microscopy of fibroblasts of four patients with variable severity and of induced pluripotent stem cell-derived neurons from two patients with developmental epileptic encephalopathies showed electron-dense inclusions, lipid droplets, osmiophilic material and lamellated membrane structures resembling phospholipids. Quantitative assessment in induced pluripotent stem cell-derived neurons identified significantly smaller lysosomes.\r\nATP6V1A-related encephalopathy represents a new paradigm among lysosomal disorders. It results from a dysfunctional endo-lysosomal membrane protein causing altered pH homeostasis. Its pathophysiology implies intracellular accumulation of substrates whose composition remains unclear, and a combination of developmental brain abnormalities and neurodegenerative changes established during prenatal and early postanal development, whose severity is variably determined by specific pathogenic variants.","lang":"eng"}],"intvolume":"       145","volume":145,"date_created":"2023-01-12T12:11:45Z","article_type":"original","day":"01","scopus_import":"1","author":[{"full_name":"Guerrini, Renzo","last_name":"Guerrini","first_name":"Renzo"},{"full_name":"Mei, Davide","last_name":"Mei","first_name":"Davide"},{"orcid":"0000-0001-9500-8758","first_name":"Margit Katalin","last_name":"Szigeti","full_name":"Szigeti, Margit Katalin","id":"44F4BDC0-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Sara","last_name":"Pepe","full_name":"Pepe, Sara"},{"full_name":"Koenig, Mary Kay","last_name":"Koenig","first_name":"Mary Kay"},{"last_name":"Von Allmen","full_name":"Von Allmen, Gretchen","first_name":"Gretchen"},{"last_name":"Cho","full_name":"Cho, Megan T","first_name":"Megan T"},{"first_name":"Kimberly","last_name":"McDonald","full_name":"McDonald, Kimberly"},{"last_name":"Baker","full_name":"Baker, Janice","first_name":"Janice"},{"first_name":"Vikas","last_name":"Bhambhani","full_name":"Bhambhani, Vikas"},{"full_name":"Powis, Zöe","last_name":"Powis","first_name":"Zöe"},{"first_name":"Lance","last_name":"Rodan","full_name":"Rodan, Lance"},{"last_name":"Nabbout","full_name":"Nabbout, Rima","first_name":"Rima"},{"first_name":"Giulia","full_name":"Barcia, Giulia","last_name":"Barcia"},{"first_name":"Jill A","last_name":"Rosenfeld","full_name":"Rosenfeld, Jill A"},{"first_name":"Carlos A","full_name":"Bacino, Carlos A","last_name":"Bacino"},{"full_name":"Mignot, Cyril","last_name":"Mignot","first_name":"Cyril"},{"full_name":"Power, Lillian H","last_name":"Power","first_name":"Lillian H"},{"full_name":"Harris, Catharine J","last_name":"Harris","first_name":"Catharine J"},{"first_name":"Dragan","full_name":"Marjanovic, Dragan","last_name":"Marjanovic"},{"full_name":"Møller, Rikke S","last_name":"Møller","first_name":"Rikke S"},{"last_name":"Hammer","full_name":"Hammer, Trine B","first_name":"Trine B"},{"last_name":"Keski Filppula","full_name":"Keski Filppula, Riikka","first_name":"Riikka"},{"last_name":"Vieira","full_name":"Vieira, Päivi","first_name":"Päivi"},{"last_name":"Hildebrandt","full_name":"Hildebrandt, Clara","first_name":"Clara"},{"first_name":"Stephanie","last_name":"Sacharow","full_name":"Sacharow, Stephanie"},{"last_name":"Maragliano","full_name":"Maragliano, Luca","first_name":"Luca"},{"first_name":"Fabio","last_name":"Benfenati","full_name":"Benfenati, Fabio"},{"last_name":"Lachlan","full_name":"Lachlan, Katherine","first_name":"Katherine"},{"first_name":"Andreas","full_name":"Benneche, Andreas","last_name":"Benneche"},{"first_name":"Florence","last_name":"Petit","full_name":"Petit, Florence"},{"full_name":"de Sainte Agathe, Jean Madeleine","last_name":"de Sainte Agathe","first_name":"Jean Madeleine"},{"first_name":"Barbara","last_name":"Hallinan","full_name":"Hallinan, Barbara"},{"first_name":"Yue","last_name":"Si","full_name":"Si, Yue"},{"last_name":"Wentzensen","full_name":"Wentzensen, Ingrid M","first_name":"Ingrid M"},{"full_name":"Zou, Fanggeng","last_name":"Zou","first_name":"Fanggeng"},{"last_name":"Narayanan","full_name":"Narayanan, Vinodh","first_name":"Vinodh"},{"full_name":"Matsumoto, Naomichi","last_name":"Matsumoto","first_name":"Naomichi"},{"last_name":"Boncristiano","full_name":"Boncristiano, Alessandra","first_name":"Alessandra"},{"last_name":"la Marca","full_name":"la Marca, Giancarlo","first_name":"Giancarlo"},{"first_name":"Mitsuhiro","full_name":"Kato, Mitsuhiro","last_name":"Kato"},{"first_name":"Kristin","last_name":"Anderson","full_name":"Anderson, Kristin"},{"first_name":"Carmen","full_name":"Barba, Carmen","last_name":"Barba"},{"first_name":"Luisa","last_name":"Sturiale","full_name":"Sturiale, Luisa"},{"last_name":"Garozzo","full_name":"Garozzo, Domenico","first_name":"Domenico"},{"first_name":"Roberto","last_name":"Bei","full_name":"Bei, Roberto"},{"first_name":"Laura","last_name":"Masuelli","full_name":"Masuelli, Laura"},{"last_name":"Conti","full_name":"Conti, Valerio","first_name":"Valerio"},{"last_name":"Novarino","full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia"},{"first_name":"Anna","full_name":"Fassio, Anna","last_name":"Fassio"}],"title":"Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal homeostasis","oa_version":"Published Version","ec_funded":1,"acknowledgement":"We thank all patients and family members for their participation in this study. We thank Melanie Pieraks and Eva Reinthaler (Neurolentech, Austria) for generating the human iPSC lines and\r\nfor performing quality checks. We thank Vanessa Zheden and Daniel Gütl for their excellent technical support in the specimen preparation for transmission electron microscopy and Flavia Leite for preparing the lentiviruses. The support from Electron Microscopy Facility and Molecular Biology Services at IST Austria is greatly acknowledged. We would like to thank Doctors Jane Hurst and Richard Scott for their help in retrieving the detailed clinical information of Patient 17. The research team acknowledges the support of the National Institute for Health Research, through the Comprehensive Clinical Research Network. See Supplementary Material for Undiagnosed Disease Network consortium details. Genetic information on Patient 23 was made available through access to the data and findings generated by the 100 000 Genomes\r\nProject; www.genomicsengland.co.uk (to K.L.). \r\nThis work was supported by the EU 7th Framework Programme (FP7) under the project DESIRE grant N602531 (to R.G.); the Regione Toscana under the Call for Health 2018 (grant\r\nDECODE-EE) (to R.G.); the ‘Brain Project’ by Fondazione Cassa di Risparmio di Firenze (to R.G.); IRCCS Ospedale Policlinico San Martino 5×1000 and Ricerca Corrente (to A.F. and F.B.). The European Reference Network (ERN) for rare and complex epilepsies (EpiCARE) provided financial support for meetings organization. The DDD study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between Wellcome and the Department of Health, and the Wellcome Sanger Institute (grant number WT098051). The views expressed in this publication\r\nare those of the author(s) and not necessarily those of Wellcome or the Department of Health. The study has UK Research Ethics Committee approval (10/H0305/83, granted by the Cambridge South REC, and GEN/284/12 granted by the Republic of Ireland REC). This study makes use of DECIPHER (https://www.deciphergenomics.org), which is funded by Wellcome. K.K.-S. was supported by the ISTplus fellowship. ","date_published":"2022-08-01T00:00:00Z","publication":"Brain","status":"public","project":[{"_id":"260C2330-B435-11E9-9278-68D0E5697425","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411","call_identifier":"H2020"}],"keyword":["Neurology (clinical)"],"isi":1,"year":"2022","external_id":{"isi":["000807770000001"]},"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1093/brain/awac145"}],"quality_controlled":"1","page":"2687-2703","_id":"12174","date_updated":"2023-08-04T09:13:08Z","type":"journal_article","article_processing_charge":"No","doi":"10.1093/brain/awac145","publisher":"Oxford University Press"},{"external_id":{"isi":["000664214100012"],"pmid":["33081568"]},"isi":1,"year":"2021","date_published":"2021-07-01T00:00:00Z","pmid":1,"publication":"Journal of Cerebral Blood Flow and Metabolism","status":"public","type":"journal_article","_id":"8730","date_updated":"2023-10-18T06:45:30Z","publisher":"SAGE Publications","article_processing_charge":"No","doi":"10.1177/0271678X20965500","quality_controlled":"1","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221757/","open_access":"1"}],"page":"1634-1646","department":[{"_id":"GaNo"}],"month":"07","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"ama":"Tournier N, Goutal S, Mairinger S, et al. Complete inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion of erlotinib and tariquidar to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib. <i>Journal of Cerebral Blood Flow and Metabolism</i>. 2021;41(7):1634-1646. doi:<a href=\"https://doi.org/10.1177/0271678X20965500\">10.1177/0271678X20965500</a>","short":"N. Tournier, S. Goutal, S. Mairinger, I. Lozano, T. Filip, M. Sauberer, F. Caillé, L. Breuil, J. Stanek, A. Freeman, G. Novarino, C. Truillet, T. Wanek, O. Langer, Journal of Cerebral Blood Flow and Metabolism 41 (2021) 1634–1646.","ieee":"N. Tournier <i>et al.</i>, “Complete inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion of erlotinib and tariquidar to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib,” <i>Journal of Cerebral Blood Flow and Metabolism</i>, vol. 41, no. 7. SAGE Publications, pp. 1634–1646, 2021.","ista":"Tournier N, Goutal S, Mairinger S, Lozano I, Filip T, Sauberer M, Caillé F, Breuil L, Stanek J, Freeman A, Novarino G, Truillet C, Wanek T, Langer O. 2021. Complete inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion of erlotinib and tariquidar to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib. Journal of Cerebral Blood Flow and Metabolism. 41(7), 1634–1646.","chicago":"Tournier, N, S Goutal, S Mairinger, IH Lozano, T Filip, M Sauberer, F Caillé, et al. “Complete Inhibition of ABCB1 and ABCG2 at the Blood-Brain Barrier by Co-Infusion of Erlotinib and Tariquidar to Improve Brain Delivery of the Model ABCB1/ABCG2 Substrate [11C]Erlotinib.” <i>Journal of Cerebral Blood Flow and Metabolism</i>. SAGE Publications, 2021. <a href=\"https://doi.org/10.1177/0271678X20965500\">https://doi.org/10.1177/0271678X20965500</a>.","mla":"Tournier, N., et al. “Complete Inhibition of ABCB1 and ABCG2 at the Blood-Brain Barrier by Co-Infusion of Erlotinib and Tariquidar to Improve Brain Delivery of the Model ABCB1/ABCG2 Substrate [11C]Erlotinib.” <i>Journal of Cerebral Blood Flow and Metabolism</i>, vol. 41, no. 7, SAGE Publications, 2021, pp. 1634–46, doi:<a href=\"https://doi.org/10.1177/0271678X20965500\">10.1177/0271678X20965500</a>.","apa":"Tournier, N., Goutal, S., Mairinger, S., Lozano, I., Filip, T., Sauberer, M., … Langer, O. (2021). Complete inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion of erlotinib and tariquidar to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib. <i>Journal of Cerebral Blood Flow and Metabolism</i>. SAGE Publications. <a href=\"https://doi.org/10.1177/0271678X20965500\">https://doi.org/10.1177/0271678X20965500</a>"},"issue":"7","language":[{"iso":"eng"}],"oa":1,"date_created":"2020-11-06T08:39:01Z","article_type":"original","volume":41,"oa_version":"Published Version","title":"Complete inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion of erlotinib and tariquidar to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib","scopus_import":"1","day":"01","author":[{"first_name":"N","last_name":"Tournier","full_name":"Tournier, N"},{"first_name":"S","full_name":"Goutal, S","last_name":"Goutal"},{"first_name":"S","last_name":"Mairinger","full_name":"Mairinger, S"},{"first_name":"IH","full_name":"Lozano, IH","last_name":"Lozano"},{"last_name":"Filip","full_name":"Filip, T","first_name":"T"},{"first_name":"M","last_name":"Sauberer","full_name":"Sauberer, M"},{"full_name":"Caillé, F","last_name":"Caillé","first_name":"F"},{"full_name":"Breuil, L","last_name":"Breuil","first_name":"L"},{"first_name":"J","full_name":"Stanek, J","last_name":"Stanek"},{"full_name":"Freeman, AF","last_name":"Freeman","first_name":"AF"},{"last_name":"Novarino","full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia"},{"first_name":"C","full_name":"Truillet, C","last_name":"Truillet"},{"full_name":"Wanek, T","last_name":"Wanek","first_name":"T"},{"first_name":"O","full_name":"Langer, O","last_name":"Langer"}],"publication_status":"published","publication_identifier":{"issn":["0271-678x"],"eissn":["1559-7016"]},"abstract":[{"lang":"eng","text":"P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) restrict at the blood–brain barrier (BBB) the brain distribution of the majority of currently known molecularly targeted anticancer drugs. To improve brain delivery of dual ABCB1/ABCG2 substrates, both ABCB1 and ABCG2 need to be inhibited simultaneously at the BBB. We examined the feasibility of simultaneous ABCB1/ABCG2 inhibition with i.v. co-infusion of erlotinib and tariquidar by studying brain distribution of the model ABCB1/ABCG2 substrate [11C]erlotinib in mice and rhesus macaques with PET. Tolerability of the erlotinib/tariquidar combination was assessed in human embryonic stem cell-derived cerebral organoids. In mice and macaques, baseline brain distribution of [11C]erlotinib was low (brain distribution volume, VT,brain < 0.3 mL/cm3). Co-infusion of erlotinib and tariquidar increased VT,brain in mice by 3.0-fold and in macaques by 3.4- to 5.0-fold, while infusion of erlotinib alone or tariquidar alone led to less pronounced VT,brain increases in both species. Treatment of cerebral organoids with erlotinib/tariquidar led to an induction of Caspase-3-dependent apoptosis. Co-infusion of erlotinib/tariquidar may potentially allow for complete ABCB1/ABCG2 inhibition at the BBB, while simultaneously achieving brain-targeted EGFR inhibition. Our protocol may be applicable to enhance brain delivery of molecularly targeted anticancer drugs for a more effective treatment of brain tumors."}],"intvolume":"        41"},{"related_material":{"link":[{"url":"https://ist.ac.at/en/news/defective-gene-slows-down-brain-cells/","relation":"press_release"}],"record":[{"status":"public","relation":"earlier_version","id":"7800"},{"relation":"dissertation_contains","status":"public","id":"12401"}]},"external_id":{"isi":["000658769900010"]},"isi":1,"year":"2021","keyword":["General Biochemistry","Genetics and Molecular Biology"],"status":"public","publication":"Nature Communications","project":[{"call_identifier":"H2020","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411","_id":"260C2330-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","_id":"25444568-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","grant_number":"W1232-B24","name":"Molecular Drug Targets","_id":"2548AE96-B435-11E9-9278-68D0E5697425"},{"grant_number":"F07807","name":"Neural stem cells in autism and epilepsy","_id":"05A0D778-7A3F-11EA-A408-12923DDC885E"},{"name":"Optical control of synaptic function via adhesion molecules","grant_number":"I03600","call_identifier":"FWF","_id":"265CB4D0-B435-11E9-9278-68D0E5697425"}],"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).","date_published":"2021-05-24T00:00:00Z","ec_funded":1,"publisher":"Springer Nature","article_processing_charge":"No","doi":"10.1038/s41467-021-23123-x","type":"journal_article","_id":"9429","date_updated":"2024-09-10T12:04:26Z","ddc":["572"],"quality_controlled":"1","month":"05","article_number":"3058","file":[{"access_level":"open_access","content_type":"application/pdf","success":1,"file_name":"2021_NatureCommunications_Morandell.pdf","checksum":"337e0f7959c35ec959984cacdcb472ba","relation":"main_file","date_updated":"2021-05-28T12:39:43Z","creator":"kschuh","file_size":9358599,"date_created":"2021-05-28T12:39:43Z","file_id":"9430"}],"department":[{"_id":"GaNo"},{"_id":"JoDa"},{"_id":"FlSc"},{"_id":"MiSi"},{"_id":"LifeSc"},{"_id":"Bio"}],"language":[{"iso":"eng"}],"oa":1,"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"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. <i>Nature Communications</i>. Springer Nature. <a href=\"https://doi.org/10.1038/s41467-021-23123-x\">https://doi.org/10.1038/s41467-021-23123-x</a>","mla":"Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” <i>Nature Communications</i>, vol. 12, no. 1, 3058, Springer Nature, 2021, doi:<a href=\"https://doi.org/10.1038/s41467-021-23123-x\">10.1038/s41467-021-23123-x</a>.","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.” <i>Nature Communications</i>. Springer Nature, 2021. <a href=\"https://doi.org/10.1038/s41467-021-23123-x\">https://doi.org/10.1038/s41467-021-23123-x</a>.","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.","ieee":"J. Morandell <i>et al.</i>, “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” <i>Nature Communications</i>, vol. 12, no. 1. Springer Nature, 2021.","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).","ama":"Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. <i>Nature Communications</i>. 2021;12(1). doi:<a href=\"https://doi.org/10.1038/s41467-021-23123-x\">10.1038/s41467-021-23123-x</a>"},"issue":"1","title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","oa_version":"Published Version","day":"24","author":[{"last_name":"Morandell","id":"4739D480-F248-11E8-B48F-1D18A9856A87","full_name":"Morandell, Jasmin","first_name":"Jasmin"},{"first_name":"Lena A","last_name":"Schwarz","full_name":"Schwarz, Lena A","id":"29A8453C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Basilico, Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","last_name":"Basilico","orcid":"0000-0003-1843-3173","first_name":"Bernadette"},{"orcid":"0000-0003-1671-393X","first_name":"Saren","last_name":"Tasciyan","full_name":"Tasciyan, Saren","id":"4323B49C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Dimchev","id":"38C393BE-F248-11E8-B48F-1D18A9856A87","full_name":"Dimchev, Georgi A","first_name":"Georgi A","orcid":"0000-0001-8370-6161"},{"first_name":"Armel","id":"2A103192-F248-11E8-B48F-1D18A9856A87","full_name":"Nicolas, Armel","last_name":"Nicolas"},{"orcid":"0000-0003-1216-9105","first_name":"Christoph M","last_name":"Sommer","full_name":"Sommer, Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Kreuzinger","full_name":"Kreuzinger, Caroline","id":"382077BA-F248-11E8-B48F-1D18A9856A87","first_name":"Caroline"},{"first_name":"Christoph","orcid":"0000-0002-9033-9096","last_name":"Dotter","full_name":"Dotter, Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Knaus","full_name":"Knaus, Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","first_name":"Lisa"},{"first_name":"Zoe","id":"D23090A2-9057-11EA-883A-A8396FC7A38F","full_name":"Dobler, Zoe","last_name":"Dobler"},{"full_name":"Cacci, Emanuele","last_name":"Cacci","first_name":"Emanuele"},{"last_name":"Schur","full_name":"Schur, Florian KM","id":"48AD8942-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4790-8078","first_name":"Florian KM"},{"orcid":"0000-0001-8559-3973","first_name":"Johann G","last_name":"Danzl","full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","orcid":"0000-0002-7673-7178","first_name":"Gaia"}],"date_created":"2021-05-28T11:49:46Z","article_type":"original","volume":12,"acknowledged_ssus":[{"_id":"PreCl"}],"intvolume":"        12","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","image":"/images/cc_by.png","short":"CC BY (4.0)"},"abstract":[{"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.","lang":"eng"}],"has_accepted_license":"1","file_date_updated":"2021-05-28T12:39:43Z","publication_status":"published","publication_identifier":{"eissn":["2041-1723"]}},{"quality_controlled":"1","ddc":["570"],"date_updated":"2023-08-14T11:46:12Z","_id":"10281","type":"journal_article","doi":"10.3390/genes12111746","article_processing_charge":"No","alternative_title":["Special Issue \"From Genes to Therapy in Autism Spectrum Disorder\""],"publisher":"MDPI","ec_funded":1,"date_published":"2021-10-30T00:00:00Z","acknowledgement":"This review was funded by the IMI2 Initiative under the grant AIMS-2-TRIALS No 777394, by the Hessian Ministry for Science and Arts; State of Hesse Ministry for Science and Arts: LOEWE-Grant to the CePTER-Consortium (www.uni-frankfurt.de/67689811); Research (BMBF) under the grant RAISE-genic No 779282 all to AGC. This work was also supported by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 (REVERSEAUTISM) and by the Austrian Science Fund (FWF) (DK W1232-B24) both to G.N. and both BMBF GeNeRARe 01GM1519A and CRC 1080, project B10, of the German Research Foundation (DFG) to M.J.S, respectively. We want to thank R. Waltes for her support in preparing this manuscript.","project":[{"grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425"},{"_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Molecular Drug Targets","grant_number":"W1232-B24"}],"status":"public","publication":"Genes","year":"2021","isi":1,"external_id":{"isi":["000834044200002"]},"publication_identifier":{"eissn":["2073-4425"]},"publication_status":"published","file_date_updated":"2022-05-16T07:02:27Z","has_accepted_license":"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","image":"/images/cc_by.png","short":"CC BY (4.0)"},"abstract":[{"text":"Mutations affecting mTOR or RAS signaling underlie defined syndromes (the so-called mTORopathies and RASopathies) with high risk for Autism Spectrum Disorder (ASD). These syndromes show a broad variety of somatic phenotypes including cancers, skin abnormalities, heart disease and facial dysmorphisms. Less well studied are the neuropsychiatric symptoms such as ASD. Here, we assess the relevance of these signalopathies in ASD reviewing genetic, human cell model, rodent studies and clinical trials. We conclude that signalopathies have an increased liability for ASD and that, in particular, ASD individuals with dysmorphic features and intellectual disability (ID) have a higher chance for disruptive mutations in RAS- and mTOR-related genes. Studies on rodent and human cell models confirm aberrant neuronal development as the underlying pathology. Human studies further suggest that multiple hits are necessary to induce the respective phenotypes. Recent clinical trials do only report improvements for comorbid conditions such as epilepsy or cancer but not for behavioral aspects. Animal models show that treatment during early development can rescue behavioral phenotypes. Taken together, we suggest investigating the differential roles of mTOR and RAS signaling in both human and rodent models, and to test drug treatment both during and after neuronal development in the available model systems","lang":"eng"}],"intvolume":"        12","volume":12,"article_type":"original","date_created":"2021-11-14T23:01:24Z","author":[{"last_name":"Vasic","full_name":"Vasic, Verica","first_name":"Verica"},{"first_name":"Mattson S.O.","last_name":"Jones","full_name":"Jones, Mattson S.O."},{"first_name":"Denise","id":"76922BDA-3D3B-11EA-90BD-A44F3DDC885E","full_name":"Haslinger, Denise","last_name":"Haslinger"},{"id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","full_name":"Knaus, Lisa","last_name":"Knaus","first_name":"Lisa"},{"full_name":"Schmeisser, Michael J.","last_name":"Schmeisser","first_name":"Michael J."},{"last_name":"Novarino","full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia"},{"full_name":"Chiocchetti, Andreas G.","last_name":"Chiocchetti","first_name":"Andreas G."}],"day":"30","scopus_import":"1","oa_version":"Published Version","title":"Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment","issue":"11","citation":{"apa":"Vasic, V., Jones, M. S. O., Haslinger, D., Knaus, L., Schmeisser, M. J., Novarino, G., &#38; Chiocchetti, A. G. (2021). Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment. <i>Genes</i>. MDPI. <a href=\"https://doi.org/10.3390/genes12111746\">https://doi.org/10.3390/genes12111746</a>","mla":"Vasic, Verica, et al. “Translating the Role of Mtor-and Ras-Associated Signalopathies in Autism Spectrum Disorder: Models, Mechanisms and Treatment.” <i>Genes</i>, vol. 12, no. 11, 1746, MDPI, 2021, doi:<a href=\"https://doi.org/10.3390/genes12111746\">10.3390/genes12111746</a>.","chicago":"Vasic, Verica, Mattson S.O. Jones, Denise Haslinger, Lisa Knaus, Michael J. Schmeisser, Gaia Novarino, and Andreas G. Chiocchetti. “Translating the Role of Mtor-and Ras-Associated Signalopathies in Autism Spectrum Disorder: Models, Mechanisms and Treatment.” <i>Genes</i>. MDPI, 2021. <a href=\"https://doi.org/10.3390/genes12111746\">https://doi.org/10.3390/genes12111746</a>.","ista":"Vasic V, Jones MSO, Haslinger D, Knaus L, Schmeisser MJ, Novarino G, Chiocchetti AG. 2021. Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment. Genes. 12(11), 1746.","ieee":"V. Vasic <i>et al.</i>, “Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment,” <i>Genes</i>, vol. 12, no. 11. MDPI, 2021.","short":"V. Vasic, M.S.O. Jones, D. Haslinger, L. Knaus, M.J. Schmeisser, G. Novarino, A.G. Chiocchetti, Genes 12 (2021).","ama":"Vasic V, Jones MSO, Haslinger D, et al. Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment. <i>Genes</i>. 2021;12(11). doi:<a href=\"https://doi.org/10.3390/genes12111746\">10.3390/genes12111746</a>"},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa":1,"language":[{"iso":"eng"}],"department":[{"_id":"GaNo"}],"file":[{"date_created":"2022-05-16T07:02:27Z","file_size":1335308,"date_updated":"2022-05-16T07:02:27Z","creator":"dernst","file_id":"11380","file_name":"2021_Genes_Vasic.pdf","success":1,"content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"256cb832a9c3051c7dc741f6423b8cbd"}],"article_number":"1746","month":"10"},{"status":"public","publication":"bioRxiv","project":[{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"I03600","name":"Optical control of synaptic function via adhesion molecules"},{"_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"W1232-B24","name":"Molecular Drug Targets"}],"date_published":"2020-01-11T00:00:00Z","year":"2020","related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"8620"},{"status":"public","relation":"later_version","id":"9429"}]},"ddc":["570"],"article_processing_charge":"No","doi":"10.1101/2020.01.10.902064 ","publisher":"Cold Spring Harbor Laboratory","_id":"7800","date_updated":"2024-09-10T12:04:26Z","type":"preprint","oa":1,"language":[{"iso":"eng"}],"citation":{"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, <a href=\"https://doi.org/10.1101/2020.01.10.902064 \">10.1101/2020.01.10.902064 </a>.","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.” <i>BioRxiv</i>. Cold Spring Harbor Laboratory, n.d. <a href=\"https://doi.org/10.1101/2020.01.10.902064 \">https://doi.org/10.1101/2020.01.10.902064 </a>.","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. <i>bioRxiv</i>. Cold Spring Harbor Laboratory. <a href=\"https://doi.org/10.1101/2020.01.10.902064 \">https://doi.org/10.1101/2020.01.10.902064 </a>","mla":"Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” <i>BioRxiv</i>, Cold Spring Harbor Laboratory, doi:<a href=\"https://doi.org/10.1101/2020.01.10.902064 \">10.1101/2020.01.10.902064 </a>.","ama":"Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. <i>bioRxiv</i>. doi:<a href=\"https://doi.org/10.1101/2020.01.10.902064 \">10.1101/2020.01.10.902064 </a>","ieee":"J. Morandell <i>et al.</i>, “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” <i>bioRxiv</i>. Cold Spring Harbor Laboratory.","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.)."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"01","department":[{"_id":"JoDa"},{"_id":"GaNo"},{"_id":"LifeSc"}],"file":[{"date_updated":"2020-07-14T12:48:03Z","creator":"rsix","date_created":"2020-05-05T14:31:19Z","file_size":2931370,"file_id":"7801","content_type":"application/pdf","access_level":"open_access","file_name":"2020.01.10.902064v1.full.pdf","checksum":"c6799ab5daba80efe8e2ed63c15f8c81","relation":"main_file"}],"has_accepted_license":"1","acknowledged_ssus":[{"_id":"PreCl"}],"tmp":{"image":"/images/cc_by_nc_nd.png","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)"},"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"}],"file_date_updated":"2020-07-14T12:48:03Z","publication_status":"submitted","day":"11","author":[{"first_name":"Jasmin","last_name":"Morandell","full_name":"Morandell, Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Lena A","full_name":"Schwarz, Lena A","id":"29A8453C-F248-11E8-B48F-1D18A9856A87","last_name":"Schwarz"},{"first_name":"Bernadette","orcid":"0000-0003-1843-3173","last_name":"Basilico","full_name":"Basilico, Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425"},{"first_name":"Saren","orcid":"0000-0003-1671-393X","id":"4323B49C-F248-11E8-B48F-1D18A9856A87","full_name":"Tasciyan, Saren","last_name":"Tasciyan"},{"first_name":"Armel","last_name":"Nicolas","id":"2A103192-F248-11E8-B48F-1D18A9856A87","full_name":"Nicolas, Armel"},{"orcid":"0000-0003-1216-9105","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M","last_name":"Sommer"},{"first_name":"Caroline","last_name":"Kreuzinger","id":"382077BA-F248-11E8-B48F-1D18A9856A87","full_name":"Kreuzinger, Caroline"},{"first_name":"Lisa","last_name":"Knaus","full_name":"Knaus, Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Dobler, Zoe","id":"D23090A2-9057-11EA-883A-A8396FC7A38F","last_name":"Dobler","first_name":"Zoe"},{"first_name":"Emanuele","last_name":"Cacci","full_name":"Cacci, Emanuele"},{"first_name":"Johann G","orcid":"0000-0001-8559-3973","last_name":"Danzl","full_name":"Danzl, Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia","last_name":"Novarino"}],"title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","oa_version":"Preprint","date_created":"2020-05-05T14:31:33Z"},{"year":"2020","isi":1,"external_id":{"isi":["000553090600008"],"pmid":["32507511"]},"status":"public","publication":"Trends in Neurosciences","project":[{"_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models"}],"ec_funded":1,"pmid":1,"date_published":"2020-08-01T00:00:00Z","acknowledgement":"We wish to thank Jasmin Morandell for generously sharing Figure 2. This work was supported by the European Research Council Starting Grant (grant 715508 ) to G.N.","article_processing_charge":"No","doi":"10.1016/j.tins.2020.05.004","publisher":"Elsevier","_id":"7957","date_updated":"2023-08-21T08:25:31Z","type":"journal_article","page":"608-621","ddc":["570"],"quality_controlled":"1","month":"08","department":[{"_id":"GaNo"}],"file":[{"file_name":"2020_TrendsNeuroscience_Parenti.pdf","success":1,"content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"67db0251b1d415ae59005f876fcf9e34","date_created":"2020-11-25T09:43:40Z","file_size":1439550,"date_updated":"2020-11-25T09:43:40Z","creator":"dernst","file_id":"8805"}],"oa":1,"language":[{"iso":"eng"}],"citation":{"ista":"Parenti I, Garcia Rabaneda LE, Schön H, Novarino G. 2020. Neurodevelopmental disorders: From genetics to functional pathways. Trends in Neurosciences. 43(8), 608–621.","chicago":"Parenti, Ilaria, Luis E Garcia Rabaneda, Hanna Schön, and Gaia Novarino. “Neurodevelopmental Disorders: From Genetics to Functional Pathways.” <i>Trends in Neurosciences</i>. Elsevier, 2020. <a href=\"https://doi.org/10.1016/j.tins.2020.05.004\">https://doi.org/10.1016/j.tins.2020.05.004</a>.","apa":"Parenti, I., Garcia Rabaneda, L. E., Schön, H., &#38; Novarino, G. (2020). Neurodevelopmental disorders: From genetics to functional pathways. <i>Trends in Neurosciences</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.tins.2020.05.004\">https://doi.org/10.1016/j.tins.2020.05.004</a>","mla":"Parenti, Ilaria, et al. “Neurodevelopmental Disorders: From Genetics to Functional Pathways.” <i>Trends in Neurosciences</i>, vol. 43, no. 8, Elsevier, 2020, pp. 608–21, doi:<a href=\"https://doi.org/10.1016/j.tins.2020.05.004\">10.1016/j.tins.2020.05.004</a>.","ama":"Parenti I, Garcia Rabaneda LE, Schön H, Novarino G. Neurodevelopmental disorders: From genetics to functional pathways. <i>Trends in Neurosciences</i>. 2020;43(8):608-621. doi:<a href=\"https://doi.org/10.1016/j.tins.2020.05.004\">10.1016/j.tins.2020.05.004</a>","ieee":"I. Parenti, L. E. Garcia Rabaneda, H. Schön, and G. Novarino, “Neurodevelopmental disorders: From genetics to functional pathways,” <i>Trends in Neurosciences</i>, vol. 43, no. 8. Elsevier, pp. 608–621, 2020.","short":"I. Parenti, L.E. Garcia Rabaneda, H. Schön, G. Novarino, Trends in Neurosciences 43 (2020) 608–621."},"issue":"8","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","day":"01","scopus_import":"1","author":[{"last_name":"Parenti","full_name":"Parenti, Ilaria","id":"D93538B0-5B71-11E9-AC62-02EBE5697425","first_name":"Ilaria"},{"first_name":"Luis E","last_name":"Garcia Rabaneda","full_name":"Garcia Rabaneda, Luis E","id":"33D1B084-F248-11E8-B48F-1D18A9856A87"},{"id":"C8E17EDC-D7AA-11E9-B7B7-45ECE5697425","full_name":"Schön, Hanna","last_name":"Schön","first_name":"Hanna"},{"orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia"}],"title":"Neurodevelopmental disorders: From genetics to functional pathways","oa_version":"Published Version","volume":43,"date_created":"2020-06-14T22:00:49Z","article_type":"original","has_accepted_license":"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","image":"/images/cc_by.png","short":"CC BY (4.0)"},"abstract":[{"lang":"eng","text":"Neurodevelopmental disorders (NDDs) are a class of disorders affecting brain development and function and are characterized by wide genetic and clinical variability. In this review, we discuss the multiple factors that influence the clinical presentation of NDDs, with particular attention to gene vulnerability, mutational load, and the two-hit model. Despite the complex architecture of\r\nmutational events associated with NDDs, the various proteins involved appear to converge on common pathways, such as synaptic plasticity/function, chromatin remodelers and the mammalian target of rapamycin (mTOR) pathway. A thorough understanding of the mechanisms behind these pathways will hopefully lead to the identification of candidates that could be targeted for treatment approaches."}],"intvolume":"        43","file_date_updated":"2020-11-25T09:43:40Z","publication_identifier":{"eissn":["1878108X"],"issn":["01662236"]},"publication_status":"published"},{"department":[{"_id":"GaNo"}],"file":[{"relation":"main_file","success":1,"file_name":"2020_CurrentOpGenetics_Basilico.pdf","access_level":"open_access","content_type":"application/pdf","file_id":"8146","file_size":1381545,"date_created":"2020-07-22T06:47:45Z","creator":"dernst","date_updated":"2020-07-22T06:47:45Z"}],"month":"12","citation":{"ama":"Basilico B, Morandell J, Novarino G. Molecular mechanisms for targeted ASD treatments. <i>Current Opinion in Genetics and Development</i>. 2020;65(12):126-137. doi:<a href=\"https://doi.org/10.1016/j.gde.2020.06.004\">10.1016/j.gde.2020.06.004</a>","ieee":"B. Basilico, J. Morandell, and G. Novarino, “Molecular mechanisms for targeted ASD treatments,” <i>Current Opinion in Genetics and Development</i>, vol. 65, no. 12. Elsevier, pp. 126–137, 2020.","short":"B. Basilico, J. Morandell, G. Novarino, Current Opinion in Genetics and Development 65 (2020) 126–137.","ista":"Basilico B, Morandell J, Novarino G. 2020. Molecular mechanisms for targeted ASD treatments. Current Opinion in Genetics and Development. 65(12), 126–137.","chicago":"Basilico, Bernadette, Jasmin Morandell, and Gaia Novarino. “Molecular Mechanisms for Targeted ASD Treatments.” <i>Current Opinion in Genetics and Development</i>. Elsevier, 2020. <a href=\"https://doi.org/10.1016/j.gde.2020.06.004\">https://doi.org/10.1016/j.gde.2020.06.004</a>.","apa":"Basilico, B., Morandell, J., &#38; Novarino, G. (2020). Molecular mechanisms for targeted ASD treatments. <i>Current Opinion in Genetics and Development</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.gde.2020.06.004\">https://doi.org/10.1016/j.gde.2020.06.004</a>","mla":"Basilico, Bernadette, et al. “Molecular Mechanisms for Targeted ASD Treatments.” <i>Current Opinion in Genetics and Development</i>, vol. 65, no. 12, Elsevier, 2020, pp. 126–37, doi:<a href=\"https://doi.org/10.1016/j.gde.2020.06.004\">10.1016/j.gde.2020.06.004</a>."},"issue":"12","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa":1,"language":[{"iso":"eng"}],"volume":65,"date_created":"2020-07-19T22:00:58Z","article_type":"original","scopus_import":"1","day":"01","author":[{"first_name":"Bernadette","orcid":"0000-0003-1843-3173","last_name":"Basilico","full_name":"Basilico, Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425"},{"first_name":"Jasmin","last_name":"Morandell","id":"4739D480-F248-11E8-B48F-1D18A9856A87","full_name":"Morandell, Jasmin"},{"orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia"}],"oa_version":"Published Version","title":"Molecular mechanisms for targeted ASD treatments","file_date_updated":"2020-07-22T06:47:45Z","publication_identifier":{"eissn":["18790380"],"issn":["0959437X"]},"publication_status":"published","has_accepted_license":"1","tmp":{"image":"/images/cc_by_nc_nd.png","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)"},"abstract":[{"text":"The possibility to generate construct valid animal models enabled the development and testing of therapeutic strategies targeting the core features of autism spectrum disorders (ASDs). At the same time, these studies highlighted the necessity of identifying sensitive developmental time windows for successful therapeutic interventions. Animal and human studies also uncovered the possibility to stratify the variety of ASDs in molecularly distinct subgroups, potentially facilitating effective treatment design. Here, we focus on the molecular pathways emerging as commonly affected by mutations in diverse ASD-risk genes, on their role during critical windows of brain development and the potential treatments targeting these biological processes.","lang":"eng"}],"intvolume":"        65","isi":1,"year":"2020","related_material":{"record":[{"id":"8620","status":"public","relation":"dissertation_contains"}]},"external_id":{"isi":["000598918900019"],"pmid":["32659636"]},"ec_funded":1,"pmid":1,"date_published":"2020-12-01T00:00:00Z","publication":"Current Opinion in Genetics and Development","status":"public","project":[{"_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411"},{"name":"Molecular Drug Targets","grant_number":"W1232-B24","call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425"},{"_id":"05A0D778-7A3F-11EA-A408-12923DDC885E","name":"Neural stem cells in autism and epilepsy","grant_number":"F07807"}],"_id":"8131","date_updated":"2024-09-10T12:04:25Z","type":"journal_article","article_processing_charge":"Yes (via OA deal)","doi":"10.1016/j.gde.2020.06.004","publisher":"Elsevier","quality_controlled":"1","page":"126-137","ddc":["570"]},{"_id":"7586","date_updated":"2023-08-18T07:07:36Z","type":"journal_article","article_processing_charge":"No","doi":"10.15252/embj.2019103358","publisher":"EMBO Press","quality_controlled":"1","ddc":["570"],"year":"2020","isi":1,"external_id":{"isi":["000517335000001"],"pmid":["32118314"]},"pmid":1,"date_published":"2020-03-02T00:00:00Z","acknowledgement":"We thank T. Stauber and T. Breiderhoff for cloning expression constructs; K. Räbel, S. Hohensee, and C. Backhaus for technical assistance; R. Jahn (MPIbpc, Göttingen) for providing the equipment required for SV purification; and A\r\nWoehler (MDC, Berlin) for assistance with SV imaging. Supported, in part, by grants from the Deutsche Forschungsgemeinschaft (JE164/9-2, SFB740 TP C5, FOR 2625 (JE164/14-1), NeuroCure Cluster of Excellence), the European Research Council Advanced Grant CYTOVOLION (ERC 294435) and the Prix Louis-Jeantet de Médecine to TJJ, and Peter and Traudl Engelhorn fellowship to ZF.","status":"public","publication":"EMBO Journal","volume":39,"date_created":"2020-03-15T23:00:55Z","article_type":"original","scopus_import":"1","day":"02","author":[{"last_name":"Weinert","full_name":"Weinert, Stefanie","first_name":"Stefanie"},{"first_name":"Niclas","full_name":"Gimber, Niclas","last_name":"Gimber"},{"first_name":"Dorothea","last_name":"Deuschel","full_name":"Deuschel, Dorothea"},{"first_name":"Till","full_name":"Stuhlmann, Till","last_name":"Stuhlmann"},{"first_name":"Dmytro","full_name":"Puchkov, Dmytro","last_name":"Puchkov"},{"full_name":"Farsi, Zohreh","last_name":"Farsi","first_name":"Zohreh"},{"first_name":"Carmen F.","full_name":"Ludwig, Carmen F.","last_name":"Ludwig"},{"orcid":"0000-0002-7673-7178","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia","last_name":"Novarino"},{"first_name":"Karen I.","full_name":"López-Cayuqueo, Karen I.","last_name":"López-Cayuqueo"},{"first_name":"Rosa","full_name":"Planells-Cases, Rosa","last_name":"Planells-Cases"},{"first_name":"Thomas J.","full_name":"Jentsch, Thomas J.","last_name":"Jentsch"}],"oa_version":"Published Version","title":"Uncoupling endosomal CLC chloride/proton exchange causes severe neurodegeneration","file_date_updated":"2020-07-14T12:48:00Z","publication_identifier":{"issn":["02614189"],"eissn":["14602075"]},"publication_status":"published","has_accepted_license":"1","tmp":{"image":"/images/cc_by_nc_nd.png","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)"},"abstract":[{"text":"CLC chloride/proton exchangers may support acidification of endolysosomes and raise their luminal Cl− concentration. Disruption of endosomal ClC‐3 causes severe neurodegeneration. To assess the importance of ClC‐3 Cl−/H+ exchange, we now generate Clcn3unc/unc mice in which ClC‐3 is converted into a Cl− channel. Unlike Clcn3−/− mice, Clcn3unc/unc mice appear normal owing to compensation by ClC‐4 with which ClC‐3 forms heteromers. ClC‐4 protein levels are strongly reduced in Clcn3−/−, but not in Clcn3unc/unc mice because ClC‐3unc binds and stabilizes ClC‐4 like wild‐type ClC‐3. Although mice lacking ClC‐4 appear healthy, its absence in Clcn3unc/unc/Clcn4−/− mice entails even stronger neurodegeneration than observed in Clcn3−/− mice. A fraction of ClC‐3 is found on synaptic vesicles, but miniature postsynaptic currents and synaptic vesicle acidification are not affected in Clcn3unc/unc or Clcn3−/− mice before neurodegeneration sets in. Both, Cl−/H+‐exchange activity and the stabilizing effect on ClC‐4, are central to the biological function of ClC‐3.","lang":"eng"}],"intvolume":"        39","department":[{"_id":"GaNo"}],"file":[{"checksum":"82750a7a93e3740decbce8474004111a","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"2020_EMBO_Weinert.pdf","file_id":"7615","creator":"dernst","date_updated":"2020-07-14T12:48:00Z","file_size":12243278,"date_created":"2020-03-23T13:51:11Z"}],"article_number":"e103358","month":"03","citation":{"chicago":"Weinert, Stefanie, Niclas Gimber, Dorothea Deuschel, Till Stuhlmann, Dmytro Puchkov, Zohreh Farsi, Carmen F. Ludwig, et al. “Uncoupling Endosomal CLC Chloride/Proton Exchange Causes Severe Neurodegeneration.” <i>EMBO Journal</i>. EMBO Press, 2020. <a href=\"https://doi.org/10.15252/embj.2019103358\">https://doi.org/10.15252/embj.2019103358</a>.","ista":"Weinert S, Gimber N, Deuschel D, Stuhlmann T, Puchkov D, Farsi Z, Ludwig CF, Novarino G, López-Cayuqueo KI, Planells-Cases R, Jentsch TJ. 2020. Uncoupling endosomal CLC chloride/proton exchange causes severe neurodegeneration. EMBO Journal. 39, e103358.","mla":"Weinert, Stefanie, et al. “Uncoupling Endosomal CLC Chloride/Proton Exchange Causes Severe Neurodegeneration.” <i>EMBO Journal</i>, vol. 39, e103358, EMBO Press, 2020, doi:<a href=\"https://doi.org/10.15252/embj.2019103358\">10.15252/embj.2019103358</a>.","apa":"Weinert, S., Gimber, N., Deuschel, D., Stuhlmann, T., Puchkov, D., Farsi, Z., … Jentsch, T. J. (2020). Uncoupling endosomal CLC chloride/proton exchange causes severe neurodegeneration. <i>EMBO Journal</i>. EMBO Press. <a href=\"https://doi.org/10.15252/embj.2019103358\">https://doi.org/10.15252/embj.2019103358</a>","ama":"Weinert S, Gimber N, Deuschel D, et al. Uncoupling endosomal CLC chloride/proton exchange causes severe neurodegeneration. <i>EMBO Journal</i>. 2020;39. doi:<a href=\"https://doi.org/10.15252/embj.2019103358\">10.15252/embj.2019103358</a>","short":"S. Weinert, N. Gimber, D. Deuschel, T. Stuhlmann, D. Puchkov, Z. Farsi, C.F. Ludwig, G. Novarino, K.I. López-Cayuqueo, R. Planells-Cases, T.J. Jentsch, EMBO Journal 39 (2020).","ieee":"S. Weinert <i>et al.</i>, “Uncoupling endosomal CLC chloride/proton exchange causes severe neurodegeneration,” <i>EMBO Journal</i>, vol. 39. EMBO Press, 2020."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa":1,"language":[{"iso":"eng"}]},{"status":"public","publication":"Brain Research","pmid":1,"date_published":"2019-12-01T00:00:00Z","year":"2019","isi":1,"external_id":{"isi":["000491646600033"],"pmid":["31521639"]},"quality_controlled":"1","doi":"10.1016/j.brainres.2019.146458","article_processing_charge":"No","publisher":"Elsevier","date_updated":"2023-08-30T06:19:49Z","_id":"6896","type":"journal_article","language":[{"iso":"eng"}],"citation":{"ieee":"B. Oliveira, A. Ç. Yahya, and G. Novarino, “Modeling cell-cell interactions in the brain using cerebral organoids,” <i>Brain Research</i>, vol. 1724. Elsevier, 2019.","short":"B. Oliveira, A.Ç. Yahya, G. Novarino, Brain Research 1724 (2019).","ama":"Oliveira B, Yahya AÇ, Novarino G. Modeling cell-cell interactions in the brain using cerebral organoids. <i>Brain Research</i>. 2019;1724. doi:<a href=\"https://doi.org/10.1016/j.brainres.2019.146458\">10.1016/j.brainres.2019.146458</a>","apa":"Oliveira, B., Yahya, A. Ç., &#38; Novarino, G. (2019). Modeling cell-cell interactions in the brain using cerebral organoids. <i>Brain Research</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.brainres.2019.146458\">https://doi.org/10.1016/j.brainres.2019.146458</a>","mla":"Oliveira, Bárbara, et al. “Modeling Cell-Cell Interactions in the Brain Using Cerebral Organoids.” <i>Brain Research</i>, vol. 1724, 146458, Elsevier, 2019, doi:<a href=\"https://doi.org/10.1016/j.brainres.2019.146458\">10.1016/j.brainres.2019.146458</a>.","ista":"Oliveira B, Yahya AÇ, Novarino G. 2019. Modeling cell-cell interactions in the brain using cerebral organoids. Brain Research. 1724, 146458.","chicago":"Oliveira, Bárbara, Aysan Çerağ Yahya, and Gaia Novarino. “Modeling Cell-Cell Interactions in the Brain Using Cerebral Organoids.” <i>Brain Research</i>. Elsevier, 2019. <a href=\"https://doi.org/10.1016/j.brainres.2019.146458\">https://doi.org/10.1016/j.brainres.2019.146458</a>."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","month":"12","department":[{"_id":"GaNo"}],"article_number":"146458","abstract":[{"lang":"eng","text":"Until recently, a great amount of brain studies have been conducted in human post mortem tissues, cell lines and model organisms. These researches provided useful insights regarding cell-cell interactions occurring in the brain. However, such approaches suffer from technical limitations and inaccurate modeling of the tissue 3D cytoarchitecture. Importantly, they might lack a human genetic background essential for disease modeling. With the development of protocols to generate human cerebral organoids, we are now closer to reproducing the early stages of human brain development in vitro. As a result, more relevant cell-cell interaction studies can be conducted.\r\n\r\nIn this review, we discuss the advantages of 3D cultures over 2D in modulating brain cell-cell interactions during physiological and pathological development, as well as the progress made in developing organoids in which neurons, macroglia, microglia and vascularization are present. Finally, we debate the limitations of those models and possible future directions."}],"intvolume":"      1724","publication_identifier":{"issn":["00068993"],"eissn":["18726240"]},"publication_status":"published","author":[{"first_name":"Bárbara","last_name":"Oliveira","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","full_name":"Oliveira, Bárbara"},{"first_name":"Aysan Çerağ","last_name":"Yahya","id":"365A65F8-F248-11E8-B48F-1D18A9856A87","full_name":"Yahya, Aysan Çerağ"},{"orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia"}],"day":"01","scopus_import":"1","oa_version":"None","title":"Modeling cell-cell interactions in the brain using cerebral organoids","volume":1724,"article_type":"original","date_created":"2019-09-22T22:00:35Z"},{"publication_identifier":{"issn":["0924-977X"]},"publication_status":"published","quality_controlled":"1","page":"S11","intvolume":"        29","date_updated":"2023-09-07T14:55:23Z","volume":29,"_id":"7414","article_type":"original","type":"journal_article","date_created":"2020-01-30T10:06:15Z","doi":"10.1016/j.euroneuro.2019.09.039","author":[{"id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","full_name":"Knaus, Lisa","last_name":"Knaus","first_name":"Lisa"},{"first_name":"Dora-Clara","last_name":"Tarlungeanu","full_name":"Tarlungeanu, Dora-Clara","id":"2ABCE612-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","first_name":"Gaia"}],"day":"13","article_processing_charge":"No","oa_version":"None","publisher":"Elsevier","title":"S.16.03 A homozygous missense mutation in SLC7A5 leads to autism spectrum disorder and microcephaly","issue":"Supplement 6","citation":{"chicago":"Knaus, Lisa, Dora-Clara Tarlungeanu, and Gaia Novarino. “S.16.03 A Homozygous Missense Mutation in SLC7A5 Leads to Autism Spectrum Disorder and Microcephaly.” <i>European Neuropsychopharmacology</i>. Elsevier, 2019. <a href=\"https://doi.org/10.1016/j.euroneuro.2019.09.039\">https://doi.org/10.1016/j.euroneuro.2019.09.039</a>.","ista":"Knaus L, Tarlungeanu D-C, Novarino G. 2019. S.16.03 A homozygous missense mutation in SLC7A5 leads to autism spectrum disorder and microcephaly. European Neuropsychopharmacology. 29(Supplement 6), S11.","mla":"Knaus, Lisa, et al. “S.16.03 A Homozygous Missense Mutation in SLC7A5 Leads to Autism Spectrum Disorder and Microcephaly.” <i>European Neuropsychopharmacology</i>, vol. 29, no. Supplement 6, Elsevier, 2019, p. S11, doi:<a href=\"https://doi.org/10.1016/j.euroneuro.2019.09.039\">10.1016/j.euroneuro.2019.09.039</a>.","apa":"Knaus, L., Tarlungeanu, D.-C., &#38; Novarino, G. (2019). S.16.03 A homozygous missense mutation in SLC7A5 leads to autism spectrum disorder and microcephaly. <i>European Neuropsychopharmacology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.euroneuro.2019.09.039\">https://doi.org/10.1016/j.euroneuro.2019.09.039</a>","ama":"Knaus L, Tarlungeanu D-C, Novarino G. S.16.03 A homozygous missense mutation in SLC7A5 leads to autism spectrum disorder and microcephaly. <i>European Neuropsychopharmacology</i>. 2019;29(Supplement 6):S11. doi:<a href=\"https://doi.org/10.1016/j.euroneuro.2019.09.039\">10.1016/j.euroneuro.2019.09.039</a>","short":"L. Knaus, D.-C. Tarlungeanu, G. Novarino, European Neuropsychopharmacology 29 (2019) S11.","ieee":"L. Knaus, D.-C. Tarlungeanu, and G. Novarino, “S.16.03 A homozygous missense mutation in SLC7A5 leads to autism spectrum disorder and microcephaly,” <i>European Neuropsychopharmacology</i>, vol. 29, no. Supplement 6. Elsevier, p. S11, 2019."},"date_published":"2019-12-13T00:00:00Z","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","language":[{"iso":"eng"}],"publication":"European Neuropsychopharmacology","status":"public","department":[{"_id":"GaNo"}],"isi":1,"year":"2019","external_id":{"isi":["000502657500020"]},"month":"12"},{"intvolume":"        29","page":"S11-S12","publication_status":"published","publication_identifier":{"issn":["0924-977X"]},"quality_controlled":"1","title":"S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism","oa_version":"None","publisher":"Elsevier","article_processing_charge":"No","day":"13","doi":"10.1016/j.euroneuro.2019.09.040","author":[{"last_name":"Morandell","full_name":"Morandell, Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","first_name":"Jasmin"},{"last_name":"Nicolas","id":"2A103192-F248-11E8-B48F-1D18A9856A87","full_name":"Nicolas, Armel","first_name":"Armel"},{"full_name":"Schwarz, Lena A","id":"29A8453C-F248-11E8-B48F-1D18A9856A87","last_name":"Schwarz","first_name":"Lena A"},{"first_name":"Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia"}],"date_created":"2020-01-30T10:07:41Z","article_type":"original","type":"journal_article","volume":29,"_id":"7415","date_updated":"2023-09-07T14:56:17Z","publication":"European Neuropsychopharmacology","language":[{"iso":"eng"}],"status":"public","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","date_published":"2019-12-13T00:00:00Z","citation":{"ama":"Morandell J, Nicolas A, Schwarz LA, Novarino G. S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism. <i>European Neuropsychopharmacology</i>. 2019;29(Supplement 6):S11-S12. doi:<a href=\"https://doi.org/10.1016/j.euroneuro.2019.09.040\">10.1016/j.euroneuro.2019.09.040</a>","short":"J. Morandell, A. Nicolas, L.A. Schwarz, G. Novarino, European Neuropsychopharmacology 29 (2019) S11–S12.","ieee":"J. Morandell, A. Nicolas, L. A. Schwarz, and G. Novarino, “S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism,” <i>European Neuropsychopharmacology</i>, vol. 29, no. Supplement 6. Elsevier, pp. S11–S12, 2019.","ista":"Morandell J, Nicolas A, Schwarz LA, Novarino G. 2019. S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism. European Neuropsychopharmacology. 29(Supplement 6), S11–S12.","chicago":"Morandell, Jasmin, Armel Nicolas, Lena A Schwarz, and Gaia Novarino. “S.16.05 Illuminating the Role of the E3 Ubiquitin Ligase Cullin3 in Brain Development and Autism.” <i>European Neuropsychopharmacology</i>. Elsevier, 2019. <a href=\"https://doi.org/10.1016/j.euroneuro.2019.09.040\">https://doi.org/10.1016/j.euroneuro.2019.09.040</a>.","mla":"Morandell, Jasmin, et al. “S.16.05 Illuminating the Role of the E3 Ubiquitin Ligase Cullin3 in Brain Development and Autism.” <i>European Neuropsychopharmacology</i>, vol. 29, no. Supplement 6, Elsevier, 2019, pp. S11–12, doi:<a href=\"https://doi.org/10.1016/j.euroneuro.2019.09.040\">10.1016/j.euroneuro.2019.09.040</a>.","apa":"Morandell, J., Nicolas, A., Schwarz, L. A., &#38; Novarino, G. (2019). S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism. <i>European Neuropsychopharmacology</i>. Elsevier. <a href=\"https://doi.org/10.1016/j.euroneuro.2019.09.040\">https://doi.org/10.1016/j.euroneuro.2019.09.040</a>"},"issue":"Supplement 6","month":"12","external_id":{"isi":["000502657500021"]},"year":"2019","isi":1,"department":[{"_id":"GaNo"},{"_id":"LifeSc"}]}]