[{"article_type":"review","page":"1066-1074","publication":"JAMA Psychiatry","citation":{"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.” JAMA Psychiatry. American Medical Association, 2023. https://doi.org/10.1001/jamapsychiatry.2023.2996.","mla":"Schumann, Gunter, et al. “Addressing Global Environmental Challenges to Mental Health Using Population Neuroscience: A Review.” JAMA Psychiatry, vol. 80, no. 10, American Medical Association, 2023, pp. 1066–74, doi:10.1001/jamapsychiatry.2023.2996.","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.","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.","ieee":"G. Schumann et al., “Addressing global environmental challenges to mental health using population neuroscience: A review,” JAMA Psychiatry, vol. 80, no. 10. American Medical Association, pp. 1066–1074, 2023.","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. JAMA Psychiatry. American Medical Association. https://doi.org/10.1001/jamapsychiatry.2023.2996","ama":"Schumann G, Andreassen OA, Banaschewski T, et al. Addressing global environmental challenges to mental health using population neuroscience: A review. JAMA Psychiatry. 2023;80(10):1066-1074. doi:10.1001/jamapsychiatry.2023.2996"},"date_published":"2023-10-01T00:00:00Z","scopus_import":"1","day":"01","article_processing_charge":"No","title":"Addressing global environmental challenges to mental health using population neuroscience: A review","status":"public","intvolume":" 80","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"14443","oa_version":"None","type":"journal_article","abstract":[{"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.","lang":"eng"}],"issue":"10","quality_controlled":"1","external_id":{"pmid":["37610741"]},"language":[{"iso":"eng"}],"doi":"10.1001/jamapsychiatry.2023.2996","month":"10","publication_identifier":{"eissn":["2168-6238"]},"publication_status":"published","department":[{"_id":"GaNo"}],"publisher":"American Medical Association","year":"2023","pmid":1,"date_created":"2023-10-22T22:01:14Z","date_updated":"2023-10-31T12:17:20Z","volume":80,"author":[{"first_name":"Gunter","last_name":"Schumann","full_name":"Schumann, Gunter"},{"first_name":"Ole A.","last_name":"Andreassen","full_name":"Andreassen, Ole A."},{"full_name":"Banaschewski, Tobias","last_name":"Banaschewski","first_name":"Tobias"},{"full_name":"Calhoun, Vince D.","first_name":"Vince D.","last_name":"Calhoun"},{"full_name":"Clinton, Nicholas","last_name":"Clinton","first_name":"Nicholas"},{"full_name":"Desrivieres, Sylvane","last_name":"Desrivieres","first_name":"Sylvane"},{"full_name":"Brandlistuen, Ragnhild Eek","last_name":"Brandlistuen","first_name":"Ragnhild Eek"},{"full_name":"Feng, Jianfeng","last_name":"Feng","first_name":"Jianfeng"},{"first_name":"Soeren","last_name":"Hese","full_name":"Hese, Soeren"},{"full_name":"Hitchen, Esther","first_name":"Esther","last_name":"Hitchen"},{"last_name":"Hoffmann","first_name":"Per","full_name":"Hoffmann, Per"},{"first_name":"Tianye","last_name":"Jia","full_name":"Jia, Tianye"},{"full_name":"Jirsa, Viktor","first_name":"Viktor","last_name":"Jirsa"},{"first_name":"Andre F.","last_name":"Marquand","full_name":"Marquand, Andre F."},{"full_name":"Nees, Frauke","last_name":"Nees","first_name":"Frauke"},{"full_name":"Nöthen, Markus M.","last_name":"Nöthen","first_name":"Markus M."},{"full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia"},{"first_name":"Elli","last_name":"Polemiti","full_name":"Polemiti, Elli"},{"full_name":"Ralser, Markus","first_name":"Markus","last_name":"Ralser"},{"last_name":"Rapp","first_name":"Michael","full_name":"Rapp, Michael"},{"last_name":"Schepanski","first_name":"Kerstin","full_name":"Schepanski, Kerstin"},{"full_name":"Schikowski, Tamara","first_name":"Tamara","last_name":"Schikowski"},{"full_name":"Slater, Mel","last_name":"Slater","first_name":"Mel"},{"last_name":"Sommer","first_name":"Peter","full_name":"Sommer, Peter"},{"first_name":"Bernd Carsten","last_name":"Stahl","full_name":"Stahl, Bernd Carsten"},{"full_name":"Thompson, Paul M.","first_name":"Paul M.","last_name":"Thompson"},{"full_name":"Twardziok, Sven","last_name":"Twardziok","first_name":"Sven"},{"full_name":"Van Der Meer, Dennis","last_name":"Van Der Meer","first_name":"Dennis"},{"last_name":"Walter","first_name":"Henrik","full_name":"Walter, Henrik"},{"full_name":"Westlye, Lars","first_name":"Lars","last_name":"Westlye"}]},{"type":"journal_article","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"}],"intvolume":" 29","title":"Effects of urban living environments on mental health in adults","status":"public","ddc":["570"],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"13168","file":[{"file_id":"13171","relation":"main_file","success":1,"checksum":"bcd3225b2731c3442fa98987fd3bd46d","date_updated":"2023-06-26T10:15:44Z","date_created":"2023-06-26T10:15:44Z","access_level":"open_access","file_name":"2023_NatureMedicine_Xu.pdf","creator":"dernst","content_type":"application/pdf","file_size":7365360}],"oa_version":"Published Version","scopus_import":"1","article_processing_charge":"No","has_accepted_license":"1","day":"15","page":"1456-1467","article_type":"original","citation":{"ama":"Xu J, Liu N, Polemiti E, et al. Effects of urban living environments on mental health in adults. Nature Medicine. 2023;29:1456-1467. doi:10.1038/s41591-023-02365-w","ieee":"J. Xu et al., “Effects of urban living environments on mental health in adults,” Nature Medicine, vol. 29. Springer Nature, pp. 1456–1467, 2023.","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. Nature Medicine. Springer Nature. https://doi.org/10.1038/s41591-023-02365-w","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.","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.","mla":"Xu, Jiayuan, et al. “Effects of Urban Living Environments on Mental Health in Adults.” Nature Medicine, vol. 29, Springer Nature, 2023, pp. 1456–67, doi:10.1038/s41591-023-02365-w.","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.” Nature Medicine. Springer Nature, 2023. https://doi.org/10.1038/s41591-023-02365-w."},"publication":"Nature Medicine","date_published":"2023-06-15T00:00:00Z","license":"https://creativecommons.org/licenses/by/4.0/","file_date_updated":"2023-06-26T10:15:44Z","department":[{"_id":"GaNo"}],"publisher":"Springer Nature","publication_status":"published","year":"2023","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.","volume":29,"date_updated":"2023-12-13T11:25:55Z","date_created":"2023-06-25T22:00:46Z","author":[{"full_name":"Xu, Jiayuan","last_name":"Xu","first_name":"Jiayuan"},{"full_name":"Liu, Nana","last_name":"Liu","first_name":"Nana"},{"first_name":"Elli","last_name":"Polemiti","full_name":"Polemiti, Elli"},{"full_name":"Garcia-Mondragon, Liliana","last_name":"Garcia-Mondragon","first_name":"Liliana"},{"first_name":"Jie","last_name":"Tang","full_name":"Tang, Jie"},{"first_name":"Xiaoxuan","last_name":"Liu","full_name":"Liu, Xiaoxuan"},{"last_name":"Lett","first_name":"Tristram","full_name":"Lett, Tristram"},{"last_name":"Yu","first_name":"Le","full_name":"Yu, Le"},{"full_name":"Nöthen, Markus M.","last_name":"Nöthen","first_name":"Markus M."},{"full_name":"Feng, Jianfeng","first_name":"Jianfeng","last_name":"Feng"},{"full_name":"Yu, Chunshui","first_name":"Chunshui","last_name":"Yu"},{"full_name":"Marquand, Andre","first_name":"Andre","last_name":"Marquand"},{"full_name":"Schumann, Gunter","last_name":"Schumann","first_name":"Gunter"},{"full_name":"Walter, Henrik","first_name":"Henrik","last_name":"Walter"},{"first_name":"Andreas","last_name":"Heinz","full_name":"Heinz, Andreas"},{"first_name":"Markus","last_name":"Ralser","full_name":"Ralser, Markus"},{"last_name":"Twardziok","first_name":"Sven","full_name":"Twardziok, Sven"},{"last_name":"Vaidya","first_name":"Nilakshi","full_name":"Vaidya, Nilakshi"},{"last_name":"Serin","first_name":"Emin","full_name":"Serin, Emin"},{"last_name":"Jentsch","first_name":"Marcel","full_name":"Jentsch, Marcel"},{"full_name":"Hitchen, Esther","last_name":"Hitchen","first_name":"Esther"},{"first_name":"Roland","last_name":"Eils","full_name":"Eils, Roland"},{"full_name":"Taron, Ulrike Helene","first_name":"Ulrike Helene","last_name":"Taron"},{"full_name":"Schütz, Tatjana","last_name":"Schütz","first_name":"Tatjana"},{"first_name":"Kerstin","last_name":"Schepanski","full_name":"Schepanski, Kerstin"},{"last_name":"Banks","first_name":"Jamie","full_name":"Banks, Jamie"},{"full_name":"Banaschewski, Tobias","last_name":"Banaschewski","first_name":"Tobias"},{"last_name":"Jansone","first_name":"Karina","full_name":"Jansone, Karina"},{"first_name":"Nina","last_name":"Christmann","full_name":"Christmann, Nina"},{"full_name":"Meyer-Lindenberg, Andreas","last_name":"Meyer-Lindenberg","first_name":"Andreas"},{"first_name":"Heike","last_name":"Tost","full_name":"Tost, Heike"},{"full_name":"Holz, Nathalie","last_name":"Holz","first_name":"Nathalie"},{"full_name":"Schwarz, Emanuel","first_name":"Emanuel","last_name":"Schwarz"},{"last_name":"Stringaris","first_name":"Argyris","full_name":"Stringaris, Argyris"},{"last_name":"Neidhart","first_name":"Maja","full_name":"Neidhart, Maja"},{"first_name":"Frauke","last_name":"Nees","full_name":"Nees, Frauke"},{"first_name":"Sebastian","last_name":"Siehl","full_name":"Siehl, Sebastian"},{"full_name":"A. Andreassen, Ole","last_name":"A. Andreassen","first_name":"Ole"},{"full_name":"T. Westlye, Lars","last_name":"T. Westlye","first_name":"Lars"},{"last_name":"Van Der Meer","first_name":"Dennis","full_name":"Van Der Meer, Dennis"},{"first_name":"Sara","last_name":"Fernandez","full_name":"Fernandez, Sara"},{"last_name":"Kjelkenes","first_name":"Rikka","full_name":"Kjelkenes, Rikka"},{"last_name":"Ask","first_name":"Helga","full_name":"Ask, Helga"},{"first_name":"Michael","last_name":"Rapp","full_name":"Rapp, Michael"},{"full_name":"Tschorn, Mira","last_name":"Tschorn","first_name":"Mira"},{"full_name":"Böttger, Sarah Jane","first_name":"Sarah Jane","last_name":"Böttger"},{"orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia","full_name":"Novarino, Gaia"},{"full_name":"Marr, Lena","id":"4406F586-F248-11E8-B48F-1D18A9856A87","first_name":"Lena","last_name":"Marr"},{"full_name":"Slater, Mel","first_name":"Mel","last_name":"Slater"},{"full_name":"Viapiana, Guillem Feixas","last_name":"Viapiana","first_name":"Guillem Feixas"},{"full_name":"Orosa, Francisco Eiroa","last_name":"Orosa","first_name":"Francisco Eiroa"},{"full_name":"Gallego, Jaime","first_name":"Jaime","last_name":"Gallego"},{"full_name":"Pastor, Alvaro","first_name":"Alvaro","last_name":"Pastor"},{"last_name":"Forstner","first_name":"Andreas","full_name":"Forstner, Andreas"},{"last_name":"Hoffmann","first_name":"Per","full_name":"Hoffmann, Per"},{"first_name":"Markus","last_name":"M. Nöthen","full_name":"M. Nöthen, Markus"},{"full_name":"J. Forstner, Andreas","first_name":"Andreas","last_name":"J. Forstner"},{"first_name":"Isabelle","last_name":"Claus","full_name":"Claus, Isabelle"},{"full_name":"Miller, Abbi","last_name":"Miller","first_name":"Abbi"},{"full_name":"Heilmann-Heimbach, Stefanie","last_name":"Heilmann-Heimbach","first_name":"Stefanie"},{"full_name":"Sommer, Peter","last_name":"Sommer","first_name":"Peter"},{"full_name":"Boye, Mona","last_name":"Boye","first_name":"Mona"},{"full_name":"Wilbertz, Johannes","last_name":"Wilbertz","first_name":"Johannes"},{"full_name":"Schmitt, Karen","last_name":"Schmitt","first_name":"Karen"},{"full_name":"Jirsa, Viktor","last_name":"Jirsa","first_name":"Viktor"},{"last_name":"Petkoski","first_name":"Spase","full_name":"Petkoski, Spase"},{"full_name":"Pitel, Séverine","last_name":"Pitel","first_name":"Séverine"},{"first_name":"Lisa","last_name":"Otten","full_name":"Otten, Lisa"},{"first_name":"Anastasios Polykarpos","last_name":"Athanasiadis","full_name":"Athanasiadis, Anastasios Polykarpos"},{"full_name":"Pearmund, Charlie","last_name":"Pearmund","first_name":"Charlie"},{"full_name":"Spanlang, Bernhard","first_name":"Bernhard","last_name":"Spanlang"},{"last_name":"Alvarez","first_name":"Elena","full_name":"Alvarez, Elena"},{"full_name":"Sanchez, Mavi","first_name":"Mavi","last_name":"Sanchez"},{"full_name":"Giner, Arantxa","last_name":"Giner","first_name":"Arantxa"},{"full_name":"Hese, Sören","last_name":"Hese","first_name":"Sören"},{"last_name":"Renner","first_name":"Paul","full_name":"Renner, Paul"},{"last_name":"Jia","first_name":"Tianye","full_name":"Jia, Tianye"},{"full_name":"Gong, Yanting","first_name":"Yanting","last_name":"Gong"},{"first_name":"Yunman","last_name":"Xia","full_name":"Xia, Yunman"},{"full_name":"Chang, Xiao","first_name":"Xiao","last_name":"Chang"},{"full_name":"Calhoun, Vince","last_name":"Calhoun","first_name":"Vince"},{"full_name":"Liu, Jingyu","first_name":"Jingyu","last_name":"Liu"},{"full_name":"Thompson, Paul","first_name":"Paul","last_name":"Thompson"},{"full_name":"Clinton, Nicholas","last_name":"Clinton","first_name":"Nicholas"},{"last_name":"Desrivieres","first_name":"Sylvane","full_name":"Desrivieres, Sylvane"},{"full_name":"H. Young, Allan","last_name":"H. Young","first_name":"Allan"},{"last_name":"Stahl","first_name":"Bernd","full_name":"Stahl, Bernd"},{"full_name":"Ogoh, George","first_name":"George","last_name":"Ogoh"}],"publication_identifier":{"issn":["1078-8956"],"eissn":["1546-170X"]},"month":"06","quality_controlled":"1","isi":1,"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["001013172700001"]},"language":[{"iso":"eng"}],"doi":"10.1038/s41591-023-02365-w"},{"day":"03","has_accepted_license":"1","article_processing_charge":"Yes","scopus_import":"1","date_published":"2023-10-03T00:00:00Z","publication":"Frontiers in Psychiatry","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. Frontiers in Psychiatry. 2023;14. doi:10.3389/fpsyt.2023.1287879","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,” Frontiers in Psychiatry, vol. 14. Frontiers, 2023.","apa":"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. Frontiers. https://doi.org/10.3389/fpsyt.2023.1287879","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.","short":"A. Narzisi, A. Halladay, G. Masi, G. Novarino, C. Lord, Frontiers in Psychiatry 14 (2023).","mla":"Narzisi, Antonio, et al. “Tempering Expectations: Considerations on the Current State of Stem Cells Therapy for Autism Treatment.” Frontiers in Psychiatry, vol. 14, 1287879, Frontiers, 2023, doi:10.3389/fpsyt.2023.1287879.","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.” Frontiers in Psychiatry. Frontiers, 2023. https://doi.org/10.3389/fpsyt.2023.1287879."},"article_type":"letter_note","type":"journal_article","file":[{"date_created":"2023-10-30T12:48:40Z","date_updated":"2023-10-30T12:48:40Z","success":1,"checksum":"0a76373e9a4c0fc199f80380de257e86","file_id":"14468","relation":"main_file","creator":"dernst","content_type":"application/pdf","file_size":147878,"file_name":"2023_FrontiersPsychiatry_Narzisi.pdf","access_level":"open_access"}],"oa_version":"Published Version","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"14455","status":"public","ddc":["570"],"title":"Tempering expectations: Considerations on the current state of stem cells therapy for autism treatment","intvolume":" 14","month":"10","publication_identifier":{"eissn":["1664-0640"]},"doi":"10.3389/fpsyt.2023.1287879","language":[{"iso":"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","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"pmid":["37854442"],"isi":["001084841700001"]},"oa":1,"isi":1,"quality_controlled":"1","file_date_updated":"2023-10-30T12:48:40Z","article_number":"1287879","author":[{"first_name":"Antonio","last_name":"Narzisi","full_name":"Narzisi, Antonio"},{"first_name":"Alycia","last_name":"Halladay","full_name":"Halladay, Alycia"},{"full_name":"Masi, Gabriele","first_name":"Gabriele","last_name":"Masi"},{"full_name":"Novarino, Gaia","first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178"},{"first_name":"Catherine","last_name":"Lord","full_name":"Lord, Catherine"}],"date_created":"2023-10-29T23:01:16Z","date_updated":"2023-12-13T13:06:07Z","volume":14,"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.","year":"2023","pmid":1,"publication_status":"published","publisher":"Frontiers","department":[{"_id":"GaNo"}]},{"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"13267","intvolume":" 20","title":"Dense 4D nanoscale reconstruction of living brain tissue","status":"public","oa_version":"Published Version","type":"journal_article","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."}],"citation":{"ieee":"P. Velicky et al., “Dense 4D nanoscale reconstruction of living brain tissue,” Nature Methods, vol. 20. Springer Nature, pp. 1256–1265, 2023.","apa":"Velicky, P., Miguel Villalba, E., Michalska, J. M., Lyudchik, J., Wei, D., Lin, Z., … Danzl, J. G. (2023). Dense 4D nanoscale reconstruction of living brain tissue. Nature Methods. Springer Nature. https://doi.org/10.1038/s41592-023-01936-6","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.","ama":"Velicky P, Miguel Villalba E, Michalska JM, et al. Dense 4D nanoscale reconstruction of living brain tissue. Nature Methods. 2023;20:1256-1265. doi:10.1038/s41592-023-01936-6","chicago":"Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Julia Lyudchik, Donglai Wei, Zudi Lin, Jake Watson, et al. “Dense 4D Nanoscale Reconstruction of Living Brain Tissue.” Nature Methods. Springer Nature, 2023. https://doi.org/10.1038/s41592-023-01936-6.","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.","mla":"Velicky, Philipp, et al. “Dense 4D Nanoscale Reconstruction of Living Brain Tissue.” Nature Methods, vol. 20, Springer Nature, 2023, pp. 1256–65, doi:10.1038/s41592-023-01936-6."},"publication":"Nature Methods","page":"1256-1265","article_type":"original","date_published":"2023-08-01T00:00:00Z","scopus_import":"1","article_processing_charge":"Yes","day":"01","pmid":1,"acknowledgement":"We thank J. Vorlaufer, N. Agudelo and A. Wartak for microscope maintenance and troubleshooting, C. Kreuzinger and A. Freeman for technical assistance, M. Šuplata for hardware control support and M. Cunha dos Santos for initial exploration of software. We\r\nthank P. Henderson for advice on deep-learning training and M. Sixt, S. Boyd and T. Weiss for discussions and critical reading of the manuscript. L. Lavis (Janelia Research Campus) generously provided the JF585-HaloTag ligand. We acknowledge expert support by IST\r\nAustria’s scientific computing, imaging and optics, preclinical, library and laboratory support facilities and by the Miba machine shop. We gratefully acknowledge funding by the following sources: Austrian Science Fund (F.W.F.) grant no. I3600-B27 (J.G.D.), grant no. DK W1232\r\n(J.G.D. and J.M.M.) and grant no. Z 312-B27, Wittgenstein award (P.J.); the Gesellschaft für Forschungsförderung NÖ grant no. LSC18-022 (J.G.D.); an ISTA Interdisciplinary project grant (J.G.D. and B.B.); the European Union’s Horizon 2020 research and innovation programme,\r\nMarie-Skłodowska Curie grant 665385 (J.M.M. and J.L.); the European Union’s Horizon 2020 research and innovation programme, European Research Council grant no. 715767, MATERIALIZABLE (B.B.); grant no. 715508, REVERSEAUTISM (G.N.); grant no. 695568, SYNNOVATE (S.G.N.G.); and grant no. 692692, GIANTSYN (P.J.); the Simons\r\nFoundation Autism Research Initiative grant no. 529085 (S.G.N.G.); the Wellcome Trust Technology Development grant no. 202932 (S.G.N.G.); the Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.);\r\nthe Human Frontier Science Program postdoctoral fellowship LT000557/2018 (W.J.); and the National Science Foundation grant no. IIS-1835231 (H.P.) and NCS-FO-2124179 (H.P.).","year":"2023","publisher":"Springer Nature","department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"},{"_id":"Bio"}],"publication_status":"published","related_material":{"link":[{"relation":"software","url":"https://github.com/danzllab/LIONESS"}],"record":[{"status":"public","relation":"research_data","id":"12817"},{"id":"14770","relation":"shorter_version","status":"public"}]},"author":[{"full_name":"Velicky, Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2340-7431","first_name":"Philipp","last_name":"Velicky"},{"orcid":"0000-0001-5665-0430","id":"3FB91342-F248-11E8-B48F-1D18A9856A87","last_name":"Miguel Villalba","first_name":"Eder","full_name":"Miguel Villalba, Eder"},{"full_name":"Michalska, Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3862-1235","first_name":"Julia M","last_name":"Michalska"},{"last_name":"Lyudchik","first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","full_name":"Lyudchik, Julia"},{"full_name":"Wei, Donglai","first_name":"Donglai","last_name":"Wei"},{"first_name":"Zudi","last_name":"Lin","full_name":"Lin, Zudi"},{"id":"63836096-4690-11EA-BD4E-32803DDC885E","orcid":"0000-0002-8698-3823","first_name":"Jake","last_name":"Watson","full_name":"Watson, Jake"},{"first_name":"Jakob","last_name":"Troidl","full_name":"Troidl, Jakob"},{"full_name":"Beyer, Johanna","first_name":"Johanna","last_name":"Beyer"},{"last_name":"Ben Simon","first_name":"Yoav","id":"43DF3136-F248-11E8-B48F-1D18A9856A87","full_name":"Ben Simon, Yoav"},{"first_name":"Christoph M","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M"},{"full_name":"Jahr, Wiebke","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","last_name":"Jahr","first_name":"Wiebke"},{"full_name":"Cenameri, Alban","first_name":"Alban","last_name":"Cenameri","id":"9ac8f577-2357-11eb-997a-e566c5550886"},{"first_name":"Johannes","last_name":"Broichhagen","full_name":"Broichhagen, Johannes"},{"last_name":"Grant","first_name":"Seth G.N.","full_name":"Grant, Seth G.N."},{"full_name":"Jonas, Peter M","first_name":"Peter M","last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804"},{"full_name":"Novarino, Gaia","last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Pfister, Hanspeter","last_name":"Pfister","first_name":"Hanspeter"},{"full_name":"Bickel, Bernd","orcid":"0000-0001-6511-9385","id":"49876194-F248-11E8-B48F-1D18A9856A87","last_name":"Bickel","first_name":"Bernd"},{"full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","last_name":"Danzl","first_name":"Johann G"}],"volume":20,"date_created":"2023-07-23T22:01:13Z","date_updated":"2024-01-10T08:37:48Z","ec_funded":1,"external_id":{"pmid":["37429995"],"isi":["001025621500001"]},"oa":1,"main_file_link":[{"url":"https://doi.org/10.1038/s41592-023-01936-6","open_access":"1"}],"project":[{"call_identifier":"FWF","name":"Optical control of synaptic function via adhesion molecules","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","grant_number":"I03600"},{"call_identifier":"FWF","name":"Molecular Drug Targets","_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24"},{"name":"The Wittgenstein Prize","call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","grant_number":"Z00312"},{"_id":"23889792-32DE-11EA-91FC-C7463DDC885E","name":"High content imaging to decode human immune cell interactions in health and allergic disease"},{"_id":"2564DBCA-B435-11E9-9278-68D0E5697425","grant_number":"665385","call_identifier":"H2020","name":"International IST Doctoral Program"},{"call_identifier":"H2020","name":"MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and Modeling","grant_number":"715767","_id":"24F9549A-B435-11E9-9278-68D0E5697425"},{"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","grant_number":"715508"},{"grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","call_identifier":"H2020"},{"_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","grant_number":"101026635","call_identifier":"H2020","name":"Synaptic computations of the hippocampal CA3 circuitry"},{"_id":"2668BFA0-B435-11E9-9278-68D0E5697425","grant_number":"LT00057","name":"High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration"}],"quality_controlled":"1","isi":1,"doi":"10.1038/s41592-023-01936-6","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"E-Lib"},{"_id":"LifeSc"},{"_id":"M-Shop"}],"publication_identifier":{"eissn":["1548-7105"],"issn":["1548-7091"]},"month":"08"},{"oa_version":"Published Version","file":[{"creator":"dernst","file_size":15712841,"content_type":"application/pdf","access_level":"open_access","file_name":"2023_Cell_Knaus.pdf","success":1,"checksum":"47e94fbe19e86505b429cb7a5b503ce6","date_updated":"2023-05-02T09:26:21Z","date_created":"2023-05-02T09:26:21Z","file_id":"12889","relation":"main_file"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"12802","title":"Large neutral amino acid levels tune perinatal neuronal excitability and survival","ddc":["570"],"status":"public","intvolume":" 186","abstract":[{"text":"Little is known about the critical metabolic changes that neural cells have to undergo during development and how temporary shifts in this program can influence brain circuitries and behavior. Inspired by the discovery that mutations in SLC7A5, a transporter of metabolically essential large neutral amino acids (LNAAs), lead to autism, we employed metabolomic profiling to study the metabolic states of the cerebral cortex across different developmental stages. We found that the forebrain undergoes significant metabolic remodeling throughout development, with certain groups of metabolites showing stage-specific changes, but what are the consequences of perturbing this metabolic program? By manipulating Slc7a5 expression in neural cells, we found that the metabolism of LNAAs and lipids are interconnected in the cortex. Deletion of Slc7a5 in neurons affects the postnatal metabolic state, leading to a shift in lipid metabolism. Additionally, it causes stage- and cell-type-specific alterations in neuronal activity patterns, resulting in a long-term circuit dysfunction.","lang":"eng"}],"issue":"9","type":"journal_article","date_published":"2023-04-27T00:00:00Z","publication":"Cell","citation":{"ama":"Knaus L, Basilico B, Malzl D, et al. Large neutral amino acid levels tune perinatal neuronal excitability and survival. Cell. 2023;186(9):1950-1967.e25. doi:10.1016/j.cell.2023.02.037","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.","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. Cell. Elsevier. https://doi.org/10.1016/j.cell.2023.02.037","ieee":"L. Knaus et al., “Large neutral amino acid levels tune perinatal neuronal excitability and survival,” Cell, vol. 186, no. 9. Elsevier, p. 1950–1967.e25, 2023.","mla":"Knaus, Lisa, et al. “Large Neutral Amino Acid Levels Tune Perinatal Neuronal Excitability and Survival.” Cell, vol. 186, no. 9, Elsevier, 2023, p. 1950–1967.e25, doi:10.1016/j.cell.2023.02.037.","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.","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.” Cell. Elsevier, 2023. https://doi.org/10.1016/j.cell.2023.02.037."},"article_type":"original","page":"1950-1967.e25","day":"27","article_processing_charge":"Yes (via OA deal)","has_accepted_license":"1","scopus_import":"1","keyword":["General Biochemistry","Genetics and Molecular Biology"],"author":[{"full_name":"Knaus, Lisa","last_name":"Knaus","first_name":"Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Basilico, Bernadette","orcid":"0000-0003-1843-3173","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","last_name":"Basilico","first_name":"Bernadette"},{"full_name":"Malzl, Daniel","last_name":"Malzl","first_name":"Daniel"},{"full_name":"Gerykova Bujalkova, Maria","last_name":"Gerykova Bujalkova","first_name":"Maria"},{"last_name":"Smogavec","first_name":"Mateja","full_name":"Smogavec, Mateja"},{"full_name":"Schwarz, Lena A.","last_name":"Schwarz","first_name":"Lena A."},{"full_name":"Gorkiewicz, Sarah","id":"f141a35d-15a9-11ec-9fb2-fef6becc7b6f","last_name":"Gorkiewicz","first_name":"Sarah"},{"full_name":"Amberg, Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3183-8207","first_name":"Nicole","last_name":"Amberg"},{"first_name":"Florian","last_name":"Pauler","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7462-0048","full_name":"Pauler, Florian"},{"last_name":"Knittl-Frank","first_name":"Christian","full_name":"Knittl-Frank, Christian"},{"full_name":"Tassinari, Marianna","last_name":"Tassinari","first_name":"Marianna","id":"7af593f1-d44a-11ed-bf94-a3646a6bb35e"},{"full_name":"Maulide, Nuno","last_name":"Maulide","first_name":"Nuno"},{"last_name":"Rülicke","first_name":"Thomas","full_name":"Rülicke, Thomas"},{"last_name":"Menche","first_name":"Jörg","full_name":"Menche, Jörg"},{"full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer","first_name":"Simon","orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"}],"related_material":{"link":[{"url":"https://ista.ac.at/en/news/feed-them-or-lose-them/","relation":"press_release","description":"News on ISTA Website"}],"record":[{"id":"13107","relation":"dissertation_contains","status":"public"}]},"date_created":"2023-04-05T08:15:40Z","date_updated":"2024-02-07T08:03:32Z","volume":186,"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.","year":"2023","publication_status":"published","department":[{"_id":"SiHi"},{"_id":"GaNo"}],"publisher":"Elsevier","file_date_updated":"2023-05-02T09:26:21Z","ec_funded":1,"doi":"10.1016/j.cell.2023.02.037","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"EM-Fac"},{"_id":"Bio"},{"_id":"LifeSc"}],"language":[{"iso":"eng"}],"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000991468700001"]},"quality_controlled":"1","isi":1,"project":[{"name":"Molecular Drug Targets","call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24"},{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","call_identifier":"H2020","grant_number":"725780","_id":"260018B0-B435-11E9-9278-68D0E5697425"},{"name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425","grant_number":"715508"}],"month":"04","publication_identifier":{"issn":["0092-8674"]}},{"date_updated":"2024-02-21T12:18:18Z","date_created":"2023-09-03T22:01:15Z","author":[{"full_name":"Michalska, Julia M","last_name":"Michalska","first_name":"Julia M","orcid":"0000-0003-3862-1235","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Lyudchik, Julia","last_name":"Lyudchik","first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Velicky","first_name":"Philipp","orcid":"0000-0002-2340-7431","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","full_name":"Velicky, Philipp"},{"full_name":"Korinkova, Hana","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","last_name":"Korinkova","first_name":"Hana"},{"id":"63836096-4690-11EA-BD4E-32803DDC885E","orcid":"0000-0002-8698-3823","first_name":"Jake","last_name":"Watson","full_name":"Watson, Jake"},{"id":"9ac8f577-2357-11eb-997a-e566c5550886","last_name":"Cenameri","first_name":"Alban","full_name":"Cenameri, Alban"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","first_name":"Christoph M","last_name":"Sommer","full_name":"Sommer, Christoph M"},{"first_name":"Nicole","last_name":"Amberg","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3183-8207","full_name":"Amberg, Nicole"},{"id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2356-9403","first_name":"Alessandro","last_name":"Venturino","full_name":"Venturino, Alessandro"},{"last_name":"Roessler","first_name":"Karl","full_name":"Roessler, Karl"},{"full_name":"Czech, Thomas","first_name":"Thomas","last_name":"Czech"},{"last_name":"Höftberger","first_name":"Romana","full_name":"Höftberger, Romana"},{"first_name":"Sandra","last_name":"Siegert","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877","full_name":"Siegert, Sandra"},{"first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","first_name":"Peter M","last_name":"Jonas","full_name":"Jonas, Peter M"},{"first_name":"Johann G","last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G"}],"related_material":{"link":[{"relation":"software","url":"https://github.com/danzllab/CATS"}],"record":[{"relation":"research_data","status":"public","id":"13126"}]},"publication_status":"epub_ahead","publisher":"Springer Nature","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"},{"_id":"Bio"},{"_id":"RySh"}],"year":"2023","acknowledgement":"We thank J. Vorlaufer, N. Agudelo-Dueñas, W. Jahr and A. Wartak for microscope maintenance and troubleshooting; C. Kreuzinger, A. Freeman and I. Erber for technical assistance; and M. Tomschik for support with obtaining human samples. We gratefully acknowledge E. Miguel for setting up webKnossos and M. Šuplata for computational support and hardware control. We are grateful to R. Shigemoto and B. Bickel for generous support and M. Sixt and S. Boyd (Stanford University) for discussions and critical reading of the paper. PSD95-HaloTag mice were kindly provided by S. Grant (University of Edinburgh). We acknowledge expert support by Institute of Science and Technology Austria’s scientific computing, imaging and optics, preclinical and lab support facilities and by the Miba machine shop and library. We gratefully acknowledge funding by the following sources: Austrian Science Fund (FWF) grant I3600-B27 (J.G.D.); Austrian Science Fund (FWF) grant DK W1232 (J.G.D. and J.M.M.); Austrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award (P.J.); Austrian Science Fund (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27 (R.H.); Gesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (J.G.D.); European Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 715508 – REVERSEAUTISM (G.N.); European Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 692692 – GIANTSYN (P.J.); Marie Skłodowska-Curie Actions Fellowship GA no. 665385 under the EU Horizon 2020 program (J.M.M. and J.L.); and Marie Skłodowska-Curie Actions Individual Fellowship no. 101026635 under the EU Horizon 2020 program (J.F.W.).","ec_funded":1,"acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"language":[{"iso":"eng"}],"doi":"10.1038/s41587-023-01911-8","isi":1,"quality_controlled":"1","project":[{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","grant_number":"I03600","name":"Optical control of synaptic function via adhesion molecules","call_identifier":"FWF"},{"call_identifier":"FWF","name":"Molecular Drug Targets","_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24"},{"grant_number":"Z00312","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"The Wittgenstein Prize"},{"_id":"23889792-32DE-11EA-91FC-C7463DDC885E","name":"High content imaging to decode human immune cell interactions in health and allergic disease"},{"call_identifier":"H2020","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","grant_number":"715508","_id":"25444568-B435-11E9-9278-68D0E5697425"},{"grant_number":"692692","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","call_identifier":"H2020"},{"name":"International IST Doctoral Program","call_identifier":"H2020","grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"},{"name":"Synaptic computations of the hippocampal CA3 circuitry","call_identifier":"H2020","grant_number":"101026635","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9"}],"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1038/s41587-023-01911-8"}],"external_id":{"isi":["001065254200001"]},"oa":1,"month":"08","publication_identifier":{"issn":["1087-0156"],"eissn":["1546-1696"]},"oa_version":"Published Version","status":"public","title":"Imaging brain tissue architecture across millimeter to nanometer scales","_id":"14257","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","abstract":[{"lang":"eng","text":"Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanometer synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS uses fixation-compatible extracellular labeling and optical imaging, including stimulated emission depletion or expansion microscopy, to comprehensively delineate cellular structures. It enables three-dimensional reconstruction of single synapses and mapping of synaptic connectivity by identification and analysis of putative synaptic cleft regions. Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed and quantified the synaptic input and output structure of identified neurons. We furthermore demonstrate applicability to clinically derived human tissue samples, including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing the cellular architecture of brain tissue in health and disease."}],"type":"journal_article","date_published":"2023-08-31T00:00:00Z","article_type":"original","publication":"Nature Biotechnology","citation":{"ieee":"J. M. Michalska et al., “Imaging brain tissue architecture across millimeter to nanometer scales,” Nature Biotechnology. Springer Nature, 2023.","apa":"Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri, A., … Danzl, J. G. (2023). Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology. Springer Nature. https://doi.org/10.1038/s41587-023-01911-8","ista":"Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer CM, Amberg N, Venturino A, Roessler K, Czech T, Höftberger R, Siegert S, Novarino G, Jonas PM, Danzl JG. 2023. Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology.","ama":"Michalska JM, Lyudchik J, Velicky P, et al. Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology. 2023. doi:10.1038/s41587-023-01911-8","chicago":"Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake Watson, Alban Cenameri, Christoph M Sommer, et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” Nature Biotechnology. Springer Nature, 2023. https://doi.org/10.1038/s41587-023-01911-8.","short":"J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri, C.M. Sommer, N. Amberg, A. Venturino, K. Roessler, T. Czech, R. Höftberger, S. Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, Nature Biotechnology (2023).","mla":"Michalska, Julia M., et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” Nature Biotechnology, Springer Nature, 2023, doi:10.1038/s41587-023-01911-8."},"day":"31","article_processing_charge":"Yes (in subscription journal)","scopus_import":"1"},{"oa_version":"Published Version","status":"public","title":"Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal homeostasis","intvolume":" 145","_id":"12174","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","abstract":[{"lang":"eng","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.\r\n 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."}],"issue":"8","type":"journal_article","date_published":"2022-08-01T00:00:00Z","article_type":"original","page":"2687-2703","publication":"Brain","citation":{"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. Brain. Oxford University Press. https://doi.org/10.1093/brain/awac145","ieee":"R. Guerrini et al., “Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal homeostasis,” Brain, vol. 145, no. 8. Oxford University Press, pp. 2687–2703, 2022.","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.","ama":"Guerrini R, Mei D, Szigeti MK, et al. Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal homeostasis. Brain. 2022;145(8):2687-2703. doi:10.1093/brain/awac145","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.” Brain. Oxford University Press, 2022. https://doi.org/10.1093/brain/awac145.","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.","mla":"Guerrini, Renzo, et al. “Phenotypic and Genetic Spectrum of ATP6V1A Encephalopathy: A Disorder of Lysosomal Homeostasis.” Brain, vol. 145, no. 8, Oxford University Press, 2022, pp. 2687–703, doi:10.1093/brain/awac145."},"day":"01","article_processing_charge":"No","keyword":["Neurology (clinical)"],"scopus_import":"1","date_updated":"2023-08-04T09:13:08Z","date_created":"2023-01-12T12:11:45Z","volume":145,"author":[{"full_name":"Guerrini, Renzo","last_name":"Guerrini","first_name":"Renzo"},{"full_name":"Mei, Davide","last_name":"Mei","first_name":"Davide"},{"full_name":"Szigeti, Margit Katalin","last_name":"Szigeti","first_name":"Margit Katalin","orcid":"0000-0001-9500-8758","id":"44F4BDC0-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Pepe, Sara","last_name":"Pepe","first_name":"Sara"},{"first_name":"Mary Kay","last_name":"Koenig","full_name":"Koenig, Mary Kay"},{"full_name":"Von Allmen, Gretchen","last_name":"Von Allmen","first_name":"Gretchen"},{"first_name":"Megan T","last_name":"Cho","full_name":"Cho, Megan T"},{"first_name":"Kimberly","last_name":"McDonald","full_name":"McDonald, Kimberly"},{"full_name":"Baker, Janice","first_name":"Janice","last_name":"Baker"},{"last_name":"Bhambhani","first_name":"Vikas","full_name":"Bhambhani, Vikas"},{"full_name":"Powis, Zöe","last_name":"Powis","first_name":"Zöe"},{"full_name":"Rodan, Lance","first_name":"Lance","last_name":"Rodan"},{"first_name":"Rima","last_name":"Nabbout","full_name":"Nabbout, Rima"},{"first_name":"Giulia","last_name":"Barcia","full_name":"Barcia, Giulia"},{"last_name":"Rosenfeld","first_name":"Jill A","full_name":"Rosenfeld, Jill A"},{"full_name":"Bacino, Carlos A","first_name":"Carlos A","last_name":"Bacino"},{"full_name":"Mignot, Cyril","last_name":"Mignot","first_name":"Cyril"},{"first_name":"Lillian H","last_name":"Power","full_name":"Power, Lillian H"},{"last_name":"Harris","first_name":"Catharine J","full_name":"Harris, Catharine J"},{"full_name":"Marjanovic, Dragan","last_name":"Marjanovic","first_name":"Dragan"},{"last_name":"Møller","first_name":"Rikke S","full_name":"Møller, Rikke S"},{"last_name":"Hammer","first_name":"Trine B","full_name":"Hammer, Trine B"},{"full_name":"Keski Filppula, Riikka","last_name":"Keski Filppula","first_name":"Riikka"},{"full_name":"Vieira, Päivi","first_name":"Päivi","last_name":"Vieira"},{"last_name":"Hildebrandt","first_name":"Clara","full_name":"Hildebrandt, Clara"},{"first_name":"Stephanie","last_name":"Sacharow","full_name":"Sacharow, Stephanie"},{"first_name":"Luca","last_name":"Maragliano","full_name":"Maragliano, Luca"},{"full_name":"Benfenati, Fabio","first_name":"Fabio","last_name":"Benfenati"},{"first_name":"Katherine","last_name":"Lachlan","full_name":"Lachlan, Katherine"},{"first_name":"Andreas","last_name":"Benneche","full_name":"Benneche, Andreas"},{"first_name":"Florence","last_name":"Petit","full_name":"Petit, Florence"},{"full_name":"de Sainte Agathe, Jean Madeleine","first_name":"Jean Madeleine","last_name":"de Sainte Agathe"},{"full_name":"Hallinan, Barbara","last_name":"Hallinan","first_name":"Barbara"},{"full_name":"Si, Yue","last_name":"Si","first_name":"Yue"},{"first_name":"Ingrid M","last_name":"Wentzensen","full_name":"Wentzensen, Ingrid M"},{"first_name":"Fanggeng","last_name":"Zou","full_name":"Zou, Fanggeng"},{"full_name":"Narayanan, Vinodh","last_name":"Narayanan","first_name":"Vinodh"},{"full_name":"Matsumoto, Naomichi","last_name":"Matsumoto","first_name":"Naomichi"},{"first_name":"Alessandra","last_name":"Boncristiano","full_name":"Boncristiano, Alessandra"},{"full_name":"la Marca, Giancarlo","first_name":"Giancarlo","last_name":"la Marca"},{"last_name":"Kato","first_name":"Mitsuhiro","full_name":"Kato, Mitsuhiro"},{"last_name":"Anderson","first_name":"Kristin","full_name":"Anderson, Kristin"},{"full_name":"Barba, Carmen","last_name":"Barba","first_name":"Carmen"},{"full_name":"Sturiale, Luisa","first_name":"Luisa","last_name":"Sturiale"},{"first_name":"Domenico","last_name":"Garozzo","full_name":"Garozzo, Domenico"},{"last_name":"Bei","first_name":"Roberto","full_name":"Bei, Roberto"},{"last_name":"Masuelli","first_name":"Laura","full_name":"Masuelli, Laura"},{"first_name":"Valerio","last_name":"Conti","full_name":"Conti, Valerio"},{"full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia"},{"full_name":"Fassio, Anna","first_name":"Anna","last_name":"Fassio"}],"publication_status":"published","department":[{"_id":"GaNo"}],"publisher":"Oxford University Press","year":"2022","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. ","ec_funded":1,"acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"LifeSc"}],"language":[{"iso":"eng"}],"doi":"10.1093/brain/awac145","isi":1,"quality_controlled":"1","project":[{"name":"ISTplus - Postdoctoral Fellowships","call_identifier":"H2020","grant_number":"754411","_id":"260C2330-B435-11E9-9278-68D0E5697425"}],"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1093/brain/awac145"}],"oa":1,"external_id":{"isi":["000807770000001"]},"month":"08","publication_identifier":{"eissn":["1460-2156"],"issn":["0006-8950"]}},{"article_processing_charge":"No","day":"09","month":"05","date_published":"2022-05-09T00:00:00Z","doi":"10.1101/2022.03.16.484431","language":[{"iso":"eng"}],"citation":{"mla":"Velicky, Philipp, et al. “Saturated Reconstruction of Living Brain Tissue.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2022.03.16.484431.","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.).","chicago":"Velicky, Philipp, Eder Miguel Villalba, Julia M Michalska, Donglai Wei, Zudi Lin, Jake Watson, Jakob Troidl, et al. “Saturated Reconstruction of Living Brain Tissue.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2022.03.16.484431.","ama":"Velicky P, Miguel Villalba E, Michalska JM, et al. Saturated reconstruction of living brain tissue. bioRxiv. doi:10.1101/2022.03.16.484431","ista":"Velicky P, Miguel Villalba E, Michalska JM, Wei D, Lin Z, Watson J, Troidl J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen J, Grant SGN, Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. Saturated reconstruction of living brain tissue. bioRxiv, 10.1101/2022.03.16.484431.","apa":"Velicky, P., Miguel Villalba, E., Michalska, J. M., Wei, D., Lin, Z., Watson, J., … Danzl, J. G. (n.d.). Saturated reconstruction of living brain tissue. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2022.03.16.484431","ieee":"P. Velicky et al., “Saturated reconstruction of living brain tissue,” bioRxiv. Cold Spring Harbor Laboratory."},"oa":1,"main_file_link":[{"url":"https://doi.org/10.1101/2022.03.16.484431","open_access":"1"}],"publication":"bioRxiv","abstract":[{"lang":"eng","text":"Complex wiring between neurons underlies the information-processing network enabling all brain functions, including cognition and memory. For understanding how the network is structured, processes information, and changes over time, comprehensive visualization of the architecture of living brain tissue with its cellular and molecular components would open up major opportunities. However, electron microscopy (EM) provides nanometre-scale resolution required for full in-silico reconstruction1–5, yet is limited to fixed specimens and static representations. Light microscopy allows live observation, with super-resolution approaches6–12 facilitating nanoscale visualization, but comprehensive 3D-reconstruction of living brain tissue has been hindered by tissue photo-burden, photobleaching, insufficient 3D-resolution, and inadequate signal-to-noise ratio (SNR). Here we demonstrate saturated reconstruction of living brain tissue. We developed an integrated imaging and analysis technology, adapting stimulated emission depletion (STED) microscopy6,13 in extracellularly labelled tissue14 for high SNR and near-isotropic resolution. Centrally, a two-stage deep-learning approach leveraged previously obtained information on sample structure to drastically reduce photo-burden and enable automated volumetric reconstruction down to single synapse level. Live reconstruction provides unbiased analysis of tissue architecture across time in relation to functional activity and targeted activation, and contextual understanding of molecular labelling. This adoptable technology will facilitate novel insights into the dynamic functional architecture of living brain tissue."}],"type":"preprint","related_material":{"record":[{"id":"12470","status":"public","relation":"dissertation_contains"}]},"author":[{"full_name":"Velicky, Philipp","first_name":"Philipp","last_name":"Velicky","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2340-7431"},{"last_name":"Miguel Villalba","first_name":"Eder","orcid":"0000-0001-5665-0430","id":"3FB91342-F248-11E8-B48F-1D18A9856A87","full_name":"Miguel Villalba, Eder"},{"full_name":"Michalska, Julia M","orcid":"0000-0003-3862-1235","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","last_name":"Michalska","first_name":"Julia M"},{"full_name":"Wei, Donglai","first_name":"Donglai","last_name":"Wei"},{"full_name":"Lin, Zudi","first_name":"Zudi","last_name":"Lin"},{"id":"63836096-4690-11EA-BD4E-32803DDC885E","orcid":"0000-0002-8698-3823","first_name":"Jake","last_name":"Watson","full_name":"Watson, Jake"},{"full_name":"Troidl, Jakob","first_name":"Jakob","last_name":"Troidl"},{"full_name":"Beyer, Johanna","last_name":"Beyer","first_name":"Johanna"},{"id":"43DF3136-F248-11E8-B48F-1D18A9856A87","last_name":"Ben Simon","first_name":"Yoav","full_name":"Ben Simon, Yoav"},{"last_name":"Sommer","first_name":"Christoph M","orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","full_name":"Sommer, Christoph M"},{"id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","first_name":"Wiebke","last_name":"Jahr","full_name":"Jahr, Wiebke"},{"id":"9ac8f577-2357-11eb-997a-e566c5550886","last_name":"Cenameri","first_name":"Alban","full_name":"Cenameri, Alban"},{"full_name":"Broichhagen, Johannes","last_name":"Broichhagen","first_name":"Johannes"},{"full_name":"Grant, Seth G. N.","last_name":"Grant","first_name":"Seth G. N."},{"full_name":"Jonas, Peter M","last_name":"Jonas","first_name":"Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia"},{"last_name":"Pfister","first_name":"Hanspeter","full_name":"Pfister, Hanspeter"},{"first_name":"Bernd","last_name":"Bickel","id":"49876194-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-6511-9385","full_name":"Bickel, Bernd"},{"id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","first_name":"Johann G","last_name":"Danzl","full_name":"Danzl, Johann G"}],"oa_version":"Preprint","date_updated":"2024-03-28T23:30:20Z","date_created":"2022-08-23T11:07:59Z","year":"2022","_id":"11943","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"}],"publisher":"Cold Spring Harbor Laboratory","status":"public","publication_status":"submitted","title":"Saturated reconstruction of living brain tissue"},{"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1101/2022.08.17.504272"}],"citation":{"chicago":"Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake Watson, Alban Cenameri, Christoph M Sommer, et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2022.08.17.504272.","short":"J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri, C.M. Sommer, A. Venturino, K. Roessler, T. Czech, S. Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, BioRxiv (n.d.).","mla":"Michalska, Julia M., et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2022.08.17.504272.","ieee":"J. M. Michalska et al., “Uncovering brain tissue architecture across scales with super-resolution light microscopy,” bioRxiv. Cold Spring Harbor Laboratory.","apa":"Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri, A., … Danzl, J. G. (n.d.). Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2022.08.17.504272","ista":"Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer CM, Venturino A, Roessler K, Czech T, Siegert S, Novarino G, Jonas PM, Danzl JG. Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv, 10.1101/2022.08.17.504272.","ama":"Michalska JM, Lyudchik J, Velicky P, et al. Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv. doi:10.1101/2022.08.17.504272"},"oa":1,"publication":"bioRxiv","doi":"10.1101/2022.08.17.504272","date_published":"2022-08-18T00:00:00Z","language":[{"iso":"eng"}],"article_processing_charge":"No","day":"18","month":"08","year":"2022","_id":"11950","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publisher":"Cold Spring Harbor Laboratory","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"}],"status":"public","title":"Uncovering brain tissue architecture across scales with super-resolution light microscopy","publication_status":"submitted","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"12470"}]},"author":[{"last_name":"Michalska","first_name":"Julia M","orcid":"0000-0003-3862-1235","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","full_name":"Michalska, Julia M"},{"last_name":"Lyudchik","first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","full_name":"Lyudchik, Julia"},{"full_name":"Velicky, Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-2340-7431","first_name":"Philipp","last_name":"Velicky"},{"id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","first_name":"Hana","last_name":"Korinkova","full_name":"Korinkova, Hana"},{"full_name":"Watson, Jake","orcid":"0000-0002-8698-3823","id":"63836096-4690-11EA-BD4E-32803DDC885E","last_name":"Watson","first_name":"Jake"},{"id":"9ac8f577-2357-11eb-997a-e566c5550886","first_name":"Alban","last_name":"Cenameri","full_name":"Cenameri, Alban"},{"full_name":"Sommer, Christoph M","last_name":"Sommer","first_name":"Christoph M","orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Venturino, Alessandro","orcid":"0000-0003-2356-9403","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","last_name":"Venturino","first_name":"Alessandro"},{"last_name":"Roessler","first_name":"Karl","full_name":"Roessler, Karl"},{"first_name":"Thomas","last_name":"Czech","full_name":"Czech, Thomas"},{"full_name":"Siegert, Sandra","first_name":"Sandra","last_name":"Siegert","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877"},{"orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia","full_name":"Novarino, Gaia"},{"full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","first_name":"Peter M"},{"full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","last_name":"Danzl","first_name":"Johann G"}],"oa_version":"Preprint","date_created":"2022-08-24T08:24:52Z","date_updated":"2024-03-28T23:30:20Z","type":"preprint","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"}]},{"file":[{"file_name":"2022_CellReports_Villa.pdf","access_level":"open_access","creator":"dernst","file_size":"7808644","content_type":"application/pdf","file_id":"11164","relation":"main_file","date_updated":"2022-04-15T09:06:25Z","date_created":"2022-04-15T09:06:25Z","success":1,"checksum":"b4e8d68f0268dec499af333e6fd5d8e1"}],"oa_version":"Published Version","_id":"11160","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","ddc":["570"],"title":"CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories","status":"public","intvolume":" 39","abstract":[{"lang":"eng","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."}],"issue":"1","type":"journal_article","date_published":"2022-04-05T00:00:00Z","publication":"Cell Reports","citation":{"ama":"Villa CE, Cheroni C, Dotter C, et al. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. Cell Reports. 2022;39(1). doi:10.1016/j.celrep.2022.110615","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.","apa":"Villa, C. E., Cheroni, C., Dotter, C., López-Tóbon, A., Oliveira, B., Sacco, R., … Novarino, G. (2022). CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. Cell Reports. Elsevier. https://doi.org/10.1016/j.celrep.2022.110615","ieee":"C. E. Villa et al., “CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories,” Cell Reports, vol. 39, no. 1. Elsevier, 2022.","mla":"Villa, Carlo Emanuele, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” Cell Reports, vol. 39, no. 1, 110615, Elsevier, 2022, doi:10.1016/j.celrep.2022.110615.","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).","chicago":"Villa, Carlo Emanuele, Cristina Cheroni, Christoph Dotter, Alejandro López-Tóbon, Bárbara Oliveira, Roberto Sacco, Aysan Çerağ Yahya, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” Cell Reports. Elsevier, 2022. https://doi.org/10.1016/j.celrep.2022.110615."},"article_type":"original","day":"05","has_accepted_license":"1","article_processing_charge":"Yes","keyword":["General Biochemistry","Genetics and Molecular Biology"],"author":[{"first_name":"Carlo Emanuele","last_name":"Villa","full_name":"Villa, Carlo Emanuele"},{"full_name":"Cheroni, Cristina","last_name":"Cheroni","first_name":"Cristina"},{"full_name":"Dotter, Christoph","orcid":"0000-0002-9033-9096","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","last_name":"Dotter","first_name":"Christoph"},{"last_name":"López-Tóbon","first_name":"Alejandro","full_name":"López-Tóbon, Alejandro"},{"first_name":"Bárbara","last_name":"Oliveira","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","full_name":"Oliveira, Bárbara"},{"last_name":"Sacco","first_name":"Roberto","id":"42C9F57E-F248-11E8-B48F-1D18A9856A87","full_name":"Sacco, Roberto"},{"last_name":"Yahya","first_name":"Aysan Çerağ","id":"365A65F8-F248-11E8-B48F-1D18A9856A87","full_name":"Yahya, Aysan Çerağ"},{"full_name":"Morandell, Jasmin","last_name":"Morandell","first_name":"Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Gabriele, Michele","last_name":"Gabriele","first_name":"Michele"},{"first_name":"Mojtaba","last_name":"Tavakoli","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7667-6854","full_name":"Tavakoli, Mojtaba"},{"full_name":"Lyudchik, Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","last_name":"Lyudchik","first_name":"Julia"},{"full_name":"Sommer, Christoph M","first_name":"Christoph M","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105"},{"last_name":"Gabitto","first_name":"Mariano","full_name":"Gabitto, Mariano"},{"full_name":"Danzl, Johann G","last_name":"Danzl","first_name":"Johann G","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Testa, Giuseppe","first_name":"Giuseppe","last_name":"Testa"},{"full_name":"Novarino, Gaia","first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178"}],"related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"12364"}]},"date_updated":"2024-03-28T23:30:45Z","date_created":"2022-04-15T09:03:10Z","volume":39,"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.","year":"2022","pmid":1,"publication_status":"published","publisher":"Elsevier","department":[{"_id":"JoDa"},{"_id":"GaNo"}],"file_date_updated":"2022-04-15T09:06:25Z","ec_funded":1,"article_number":"110615","doi":"10.1016/j.celrep.2022.110615","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"language":[{"iso":"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","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000785983900003"],"pmid":["35385734"]},"oa":1,"quality_controlled":"1","isi":1,"project":[{"call_identifier":"H2020","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","grant_number":"715508","_id":"25444568-B435-11E9-9278-68D0E5697425"},{"name":"Identification of converging Molecular Pathways Across Chromatinopathies as Targets for Therapy","call_identifier":"FWF","_id":"2690FEAC-B435-11E9-9278-68D0E5697425","grant_number":"I04205"}],"month":"04","publication_identifier":{"issn":["2211-1247"]}},{"title":"Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment","ddc":["570"],"status":"public","intvolume":" 12","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"10281","oa_version":"Published Version","file":[{"access_level":"open_access","file_name":"2021_Genes_Vasic.pdf","creator":"dernst","file_size":1335308,"content_type":"application/pdf","file_id":"11380","relation":"main_file","success":1,"checksum":"256cb832a9c3051c7dc741f6423b8cbd","date_updated":"2022-05-16T07:02:27Z","date_created":"2022-05-16T07:02:27Z"}],"alternative_title":["Special Issue \"From Genes to Therapy in Autism Spectrum Disorder\""],"type":"journal_article","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"}],"issue":"11","article_type":"original","publication":"Genes","citation":{"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.” Genes. MDPI, 2021. https://doi.org/10.3390/genes12111746.","mla":"Vasic, Verica, et al. “Translating the Role of Mtor-and Ras-Associated Signalopathies in Autism Spectrum Disorder: Models, Mechanisms and Treatment.” Genes, vol. 12, no. 11, 1746, MDPI, 2021, doi:10.3390/genes12111746.","short":"V. Vasic, M.S.O. Jones, D. Haslinger, L. Knaus, M.J. Schmeisser, G. Novarino, A.G. Chiocchetti, Genes 12 (2021).","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.","apa":"Vasic, V., Jones, M. S. O., Haslinger, D., Knaus, L., Schmeisser, M. J., Novarino, G., & Chiocchetti, A. G. (2021). Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment. Genes. MDPI. https://doi.org/10.3390/genes12111746","ieee":"V. Vasic et al., “Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment,” Genes, vol. 12, no. 11. MDPI, 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. Genes. 2021;12(11). doi:10.3390/genes12111746"},"date_published":"2021-10-30T00:00:00Z","scopus_import":"1","day":"30","article_processing_charge":"No","has_accepted_license":"1","publication_status":"published","publisher":"MDPI","department":[{"_id":"GaNo"}],"year":"2021","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.","date_created":"2021-11-14T23:01:24Z","date_updated":"2023-08-14T11:46:12Z","volume":12,"author":[{"full_name":"Vasic, Verica","last_name":"Vasic","first_name":"Verica"},{"full_name":"Jones, Mattson S.O.","last_name":"Jones","first_name":"Mattson S.O."},{"full_name":"Haslinger, Denise","id":"76922BDA-3D3B-11EA-90BD-A44F3DDC885E","first_name":"Denise","last_name":"Haslinger"},{"full_name":"Knaus, Lisa","last_name":"Knaus","first_name":"Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Schmeisser","first_name":"Michael J.","full_name":"Schmeisser, Michael J."},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino","full_name":"Novarino, Gaia"},{"last_name":"Chiocchetti","first_name":"Andreas G.","full_name":"Chiocchetti, Andreas G."}],"article_number":"1746","file_date_updated":"2022-05-16T07:02:27Z","ec_funded":1,"isi":1,"quality_controlled":"1","project":[{"grant_number":"715508","_id":"25444568-B435-11E9-9278-68D0E5697425","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020"},{"name":"Molecular Drug Targets","call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"external_id":{"isi":["000834044200002"]},"language":[{"iso":"eng"}],"doi":"10.3390/genes12111746","month":"10","publication_identifier":{"eissn":["2073-4425"]}},{"status":"public","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","intvolume":" 41","_id":"8730","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"Published Version","type":"journal_article","abstract":[{"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.","lang":"eng"}],"issue":"7","article_type":"original","page":"1634-1646","publication":"Journal of Cerebral Blood Flow and Metabolism","citation":{"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.","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.” Journal of Cerebral Blood Flow and Metabolism, vol. 41, no. 7, SAGE Publications, 2021, pp. 1634–46, doi:10.1177/0271678X20965500.","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.” Journal of Cerebral Blood Flow and Metabolism. SAGE Publications, 2021. https://doi.org/10.1177/0271678X20965500.","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. Journal of Cerebral Blood Flow and Metabolism. 2021;41(7):1634-1646. doi:10.1177/0271678X20965500","ieee":"N. Tournier 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,” Journal of Cerebral Blood Flow and Metabolism, vol. 41, no. 7. SAGE Publications, pp. 1634–1646, 2021.","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. Journal of Cerebral Blood Flow and Metabolism. SAGE Publications. https://doi.org/10.1177/0271678X20965500","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."},"date_published":"2021-07-01T00:00:00Z","scopus_import":"1","day":"01","article_processing_charge":"No","publication_status":"published","publisher":"SAGE Publications","department":[{"_id":"GaNo"}],"year":"2021","pmid":1,"date_updated":"2023-10-18T06:45:30Z","date_created":"2020-11-06T08:39:01Z","volume":41,"author":[{"first_name":"N","last_name":"Tournier","full_name":"Tournier, N"},{"last_name":"Goutal","first_name":"S","full_name":"Goutal, S"},{"full_name":"Mairinger, S","first_name":"S","last_name":"Mairinger"},{"full_name":"Lozano, IH","first_name":"IH","last_name":"Lozano"},{"full_name":"Filip, T","last_name":"Filip","first_name":"T"},{"full_name":"Sauberer, M","last_name":"Sauberer","first_name":"M"},{"first_name":"F","last_name":"Caillé","full_name":"Caillé, F"},{"first_name":"L","last_name":"Breuil","full_name":"Breuil, L"},{"last_name":"Stanek","first_name":"J","full_name":"Stanek, J"},{"first_name":"AF","last_name":"Freeman","full_name":"Freeman, AF"},{"full_name":"Novarino, Gaia","first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178"},{"first_name":"C","last_name":"Truillet","full_name":"Truillet, C"},{"full_name":"Wanek, T","first_name":"T","last_name":"Wanek"},{"first_name":"O","last_name":"Langer","full_name":"Langer, O"}],"quality_controlled":"1","isi":1,"oa":1,"main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221757/","open_access":"1"}],"external_id":{"pmid":["33081568"],"isi":["000664214100012"]},"language":[{"iso":"eng"}],"doi":"10.1177/0271678X20965500","month":"07","publication_identifier":{"issn":["0271-678x"],"eissn":["1559-7016"]}},{"type":"journal_article","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"}],"issue":"1","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"9429","status":"public","title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","ddc":["572"],"intvolume":" 12","oa_version":"Published Version","file":[{"file_name":"2021_NatureCommunications_Morandell.pdf","access_level":"open_access","file_size":9358599,"content_type":"application/pdf","creator":"kschuh","relation":"main_file","file_id":"9430","date_updated":"2021-05-28T12:39:43Z","date_created":"2021-05-28T12:39:43Z","checksum":"337e0f7959c35ec959984cacdcb472ba","success":1}],"keyword":["General Biochemistry","Genetics and Molecular Biology"],"day":"24","article_processing_charge":"No","has_accepted_license":"1","publication":"Nature Communications","citation":{"ama":"Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. 2021;12(1). doi:10.1038/s41467-021-23123-x","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 et al., “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” Nature Communications, vol. 12, no. 1. Springer Nature, 2021.","apa":"Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Dimchev, G. A., Nicolas, A., … Novarino, G. (2021). Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-021-23123-x","mla":"Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” Nature Communications, vol. 12, no. 1, 3058, Springer Nature, 2021, doi:10.1038/s41467-021-23123-x.","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).","chicago":"Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan, Georgi A Dimchev, Armel Nicolas, Christoph M Sommer, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” Nature Communications. Springer Nature, 2021. https://doi.org/10.1038/s41467-021-23123-x."},"article_type":"original","date_published":"2021-05-24T00:00:00Z","article_number":"3058","file_date_updated":"2021-05-28T12:39:43Z","ec_funded":1,"acknowledgement":"We thank A. Coll Manzano, F. Freeman, M. Ladron de Guevara, and A. Ç. Yahya for technical assistance, S. Deixler, A. Lepold, and A. Schlerka for the management of our animal colony, as well as M. Schunn and the Preclinical Facility team for technical assistance. We thank K. Heesom and her team at the University of Bristol Proteomics Facility for the proteomics sample preparation, data generation, and analysis support. We thank Y. B. Simon for kindly providing the plasmid for lentiviral labeling. Further, we thank M. Sixt for his advice regarding cell migration and the fruitful discussions. This work was supported by the ISTPlus postdoctoral fellowship (Grant Agreement No. 754411) to B.B., by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 (REVERSEAUTISM), and by the Austrian Science Fund (FWF) to G.N. (DK W1232-B24 and SFB F7807-B) and to J.G.D (I3600-B27).","year":"2021","publication_status":"published","publisher":"Springer Nature","department":[{"_id":"GaNo"},{"_id":"JoDa"},{"_id":"FlSc"},{"_id":"MiSi"},{"_id":"LifeSc"},{"_id":"Bio"}],"author":[{"full_name":"Morandell, Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","first_name":"Jasmin","last_name":"Morandell"},{"last_name":"Schwarz","first_name":"Lena A","id":"29A8453C-F248-11E8-B48F-1D18A9856A87","full_name":"Schwarz, Lena A"},{"full_name":"Basilico, Bernadette","orcid":"0000-0003-1843-3173","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","last_name":"Basilico","first_name":"Bernadette"},{"full_name":"Tasciyan, Saren","last_name":"Tasciyan","first_name":"Saren","orcid":"0000-0003-1671-393X","id":"4323B49C-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Georgi A","last_name":"Dimchev","id":"38C393BE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8370-6161","full_name":"Dimchev, Georgi A"},{"id":"2A103192-F248-11E8-B48F-1D18A9856A87","last_name":"Nicolas","first_name":"Armel","full_name":"Nicolas, Armel"},{"full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","last_name":"Sommer","first_name":"Christoph M"},{"full_name":"Kreuzinger, Caroline","first_name":"Caroline","last_name":"Kreuzinger","id":"382077BA-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Dotter, Christoph","orcid":"0000-0002-9033-9096","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","last_name":"Dotter","first_name":"Christoph"},{"first_name":"Lisa","last_name":"Knaus","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","full_name":"Knaus, Lisa"},{"full_name":"Dobler, Zoe","id":"D23090A2-9057-11EA-883A-A8396FC7A38F","first_name":"Zoe","last_name":"Dobler"},{"full_name":"Cacci, Emanuele","last_name":"Cacci","first_name":"Emanuele"},{"full_name":"Schur, Florian KM","id":"48AD8942-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-4790-8078","first_name":"Florian KM","last_name":"Schur"},{"full_name":"Danzl, Johann G","first_name":"Johann G","last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973"},{"full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia"}],"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"}]},"date_updated":"2024-03-28T23:30:23Z","date_created":"2021-05-28T11:49:46Z","volume":12,"month":"05","publication_identifier":{"eissn":["2041-1723"]},"external_id":{"isi":["000658769900010"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"isi":1,"quality_controlled":"1","project":[{"name":"ISTplus - Postdoctoral Fellowships","call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411"},{"call_identifier":"H2020","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","_id":"25444568-B435-11E9-9278-68D0E5697425","grant_number":"715508"},{"grant_number":"W1232-B24","_id":"2548AE96-B435-11E9-9278-68D0E5697425","name":"Molecular Drug Targets","call_identifier":"FWF"},{"name":"Neural stem cells in autism and epilepsy","grant_number":"F07807","_id":"05A0D778-7A3F-11EA-A408-12923DDC885E"},{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","grant_number":"I03600","call_identifier":"FWF","name":"Optical control of synaptic function via adhesion molecules"}],"doi":"10.1038/s41467-021-23123-x","acknowledged_ssus":[{"_id":"PreCl"}],"language":[{"iso":"eng"}]},{"month":"03","publication_identifier":{"eissn":["14602075"],"issn":["02614189"]},"oa":1,"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"external_id":{"isi":["000517335000001"],"pmid":["32118314"]},"isi":1,"quality_controlled":"1","doi":"10.15252/embj.2019103358","language":[{"iso":"eng"}],"article_number":"e103358","file_date_updated":"2020-07-14T12:48:00Z","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","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.","year":"2020","pmid":1,"publication_status":"published","department":[{"_id":"GaNo"}],"publisher":"EMBO Press","author":[{"full_name":"Weinert, Stefanie","first_name":"Stefanie","last_name":"Weinert"},{"full_name":"Gimber, Niclas","last_name":"Gimber","first_name":"Niclas"},{"full_name":"Deuschel, Dorothea","first_name":"Dorothea","last_name":"Deuschel"},{"first_name":"Till","last_name":"Stuhlmann","full_name":"Stuhlmann, Till"},{"full_name":"Puchkov, Dmytro","first_name":"Dmytro","last_name":"Puchkov"},{"full_name":"Farsi, Zohreh","last_name":"Farsi","first_name":"Zohreh"},{"full_name":"Ludwig, Carmen F.","first_name":"Carmen F.","last_name":"Ludwig"},{"last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia"},{"first_name":"Karen I.","last_name":"López-Cayuqueo","full_name":"López-Cayuqueo, Karen I."},{"full_name":"Planells-Cases, Rosa","last_name":"Planells-Cases","first_name":"Rosa"},{"full_name":"Jentsch, Thomas J.","first_name":"Thomas J.","last_name":"Jentsch"}],"date_updated":"2023-08-18T07:07:36Z","date_created":"2020-03-15T23:00:55Z","volume":39,"scopus_import":"1","day":"02","has_accepted_license":"1","article_processing_charge":"No","publication":"EMBO Journal","citation":{"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.","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. EMBO Journal. EMBO Press. https://doi.org/10.15252/embj.2019103358","ieee":"S. Weinert et al., “Uncoupling endosomal CLC chloride/proton exchange causes severe neurodegeneration,” EMBO Journal, vol. 39. EMBO Press, 2020.","ama":"Weinert S, Gimber N, Deuschel D, et al. Uncoupling endosomal CLC chloride/proton exchange causes severe neurodegeneration. EMBO Journal. 2020;39. doi:10.15252/embj.2019103358","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.” EMBO Journal. EMBO Press, 2020. https://doi.org/10.15252/embj.2019103358.","mla":"Weinert, Stefanie, et al. “Uncoupling Endosomal CLC Chloride/Proton Exchange Causes Severe Neurodegeneration.” EMBO Journal, vol. 39, e103358, EMBO Press, 2020, doi:10.15252/embj.2019103358.","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)."},"article_type":"original","date_published":"2020-03-02T00:00:00Z","type":"journal_article","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"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"7586","title":"Uncoupling endosomal CLC chloride/proton exchange causes severe neurodegeneration","ddc":["570"],"status":"public","intvolume":" 39","file":[{"access_level":"open_access","file_name":"2020_EMBO_Weinert.pdf","file_size":12243278,"content_type":"application/pdf","creator":"dernst","relation":"main_file","file_id":"7615","checksum":"82750a7a93e3740decbce8474004111a","date_created":"2020-03-23T13:51:11Z","date_updated":"2020-07-14T12:48:00Z"}],"oa_version":"Published Version"},{"file":[{"success":1,"checksum":"67db0251b1d415ae59005f876fcf9e34","date_updated":"2020-11-25T09:43:40Z","date_created":"2020-11-25T09:43:40Z","file_id":"8805","relation":"main_file","creator":"dernst","file_size":1439550,"content_type":"application/pdf","access_level":"open_access","file_name":"2020_TrendsNeuroscience_Parenti.pdf"}],"oa_version":"Published Version","_id":"7957","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","intvolume":" 43","ddc":["570"],"title":"Neurodevelopmental disorders: From genetics to functional pathways","status":"public","issue":"8","abstract":[{"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.","lang":"eng"}],"type":"journal_article","date_published":"2020-08-01T00:00:00Z","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.","apa":"Parenti, I., Garcia Rabaneda, L. E., Schön, H., & Novarino, G. (2020). Neurodevelopmental disorders: From genetics to functional pathways. Trends in Neurosciences. Elsevier. https://doi.org/10.1016/j.tins.2020.05.004","ieee":"I. Parenti, L. E. Garcia Rabaneda, H. Schön, and G. Novarino, “Neurodevelopmental disorders: From genetics to functional pathways,” Trends in Neurosciences, vol. 43, no. 8. Elsevier, pp. 608–621, 2020.","ama":"Parenti I, Garcia Rabaneda LE, Schön H, Novarino G. Neurodevelopmental disorders: From genetics to functional pathways. Trends in Neurosciences. 2020;43(8):608-621. doi:10.1016/j.tins.2020.05.004","chicago":"Parenti, Ilaria, Luis E Garcia Rabaneda, Hanna Schön, and Gaia Novarino. “Neurodevelopmental Disorders: From Genetics to Functional Pathways.” Trends in Neurosciences. Elsevier, 2020. https://doi.org/10.1016/j.tins.2020.05.004.","mla":"Parenti, Ilaria, et al. “Neurodevelopmental Disorders: From Genetics to Functional Pathways.” Trends in Neurosciences, vol. 43, no. 8, Elsevier, 2020, pp. 608–21, doi:10.1016/j.tins.2020.05.004.","short":"I. Parenti, L.E. Garcia Rabaneda, H. Schön, G. Novarino, Trends in Neurosciences 43 (2020) 608–621."},"publication":"Trends in Neurosciences","page":"608-621","article_type":"original","article_processing_charge":"No","has_accepted_license":"1","day":"01","scopus_import":"1","author":[{"id":"D93538B0-5B71-11E9-AC62-02EBE5697425","last_name":"Parenti","first_name":"Ilaria","full_name":"Parenti, Ilaria"},{"id":"33D1B084-F248-11E8-B48F-1D18A9856A87","first_name":"Luis E","last_name":"Garcia Rabaneda","full_name":"Garcia Rabaneda, Luis E"},{"id":"C8E17EDC-D7AA-11E9-B7B7-45ECE5697425","last_name":"Schön","first_name":"Hanna","full_name":"Schön, Hanna"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino","full_name":"Novarino, Gaia"}],"volume":43,"date_updated":"2023-08-21T08:25:31Z","date_created":"2020-06-14T22:00:49Z","pmid":1,"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.","year":"2020","department":[{"_id":"GaNo"}],"publisher":"Elsevier","publication_status":"published","ec_funded":1,"file_date_updated":"2020-11-25T09:43:40Z","doi":"10.1016/j.tins.2020.05.004","language":[{"iso":"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","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000553090600008"],"pmid":["32507511"]},"oa":1,"project":[{"_id":"25444568-B435-11E9-9278-68D0E5697425","grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020"}],"isi":1,"quality_controlled":"1","publication_identifier":{"eissn":["1878108X"],"issn":["01662236"]},"month":"08"},{"day":"11","article_processing_charge":"No","has_accepted_license":"1","publication":"bioRxiv","citation":{"ieee":"J. Morandell et al., “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” bioRxiv. Cold Spring Harbor Laboratory.","apa":"Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Nicolas, A., Sommer, C. M., … Novarino, G. (n.d.). Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.01.10.902064 ","ista":"Morandell J, Schwarz LA, Basilico B, Tasciyan S, Nicolas A, Sommer CM, Kreuzinger C, Knaus L, Dobler Z, Cacci E, Danzl JG, Novarino G. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. bioRxiv, 10.1101/2020.01.10.902064 .","ama":"Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. bioRxiv. doi:10.1101/2020.01.10.902064 ","chicago":"Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan, Armel Nicolas, Christoph M Sommer, Caroline Kreuzinger, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” BioRxiv. Cold Spring Harbor Laboratory, n.d. https://doi.org/10.1101/2020.01.10.902064 .","short":"J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, A. Nicolas, C.M. Sommer, C. Kreuzinger, L. Knaus, Z. Dobler, E. Cacci, J.G. Danzl, G. Novarino, BioRxiv (n.d.).","mla":"Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2020.01.10.902064 ."},"date_published":"2020-01-11T00:00:00Z","type":"preprint","abstract":[{"lang":"eng","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."}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"7800","status":"public","title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","ddc":["570"],"file":[{"file_name":"2020.01.10.902064v1.full.pdf","access_level":"open_access","creator":"rsix","content_type":"application/pdf","file_size":2931370,"file_id":"7801","relation":"main_file","date_updated":"2020-07-14T12:48:03Z","date_created":"2020-05-05T14:31:19Z","checksum":"c6799ab5daba80efe8e2ed63c15f8c81"}],"oa_version":"Preprint","month":"01","oa":1,"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"project":[{"call_identifier":"FWF","name":"Optical control of synaptic function via adhesion molecules","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","grant_number":"I03600"},{"_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24","call_identifier":"FWF","name":"Molecular Drug Targets"}],"doi":"10.1101/2020.01.10.902064 ","acknowledged_ssus":[{"_id":"PreCl"}],"language":[{"iso":"eng"}],"file_date_updated":"2020-07-14T12:48:03Z","year":"2020","publication_status":"submitted","department":[{"_id":"JoDa"},{"_id":"GaNo"},{"_id":"LifeSc"}],"publisher":"Cold Spring Harbor Laboratory","author":[{"full_name":"Morandell, Jasmin","last_name":"Morandell","first_name":"Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87"},{"id":"29A8453C-F248-11E8-B48F-1D18A9856A87","last_name":"Schwarz","first_name":"Lena A","full_name":"Schwarz, Lena A"},{"full_name":"Basilico, Bernadette","orcid":"0000-0003-1843-3173","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","last_name":"Basilico","first_name":"Bernadette"},{"orcid":"0000-0003-1671-393X","id":"4323B49C-F248-11E8-B48F-1D18A9856A87","last_name":"Tasciyan","first_name":"Saren","full_name":"Tasciyan, Saren"},{"last_name":"Nicolas","first_name":"Armel","id":"2A103192-F248-11E8-B48F-1D18A9856A87","full_name":"Nicolas, Armel"},{"first_name":"Christoph M","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M"},{"last_name":"Kreuzinger","first_name":"Caroline","id":"382077BA-F248-11E8-B48F-1D18A9856A87","full_name":"Kreuzinger, Caroline"},{"id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","first_name":"Lisa","last_name":"Knaus","full_name":"Knaus, Lisa"},{"full_name":"Dobler, Zoe","id":"D23090A2-9057-11EA-883A-A8396FC7A38F","first_name":"Zoe","last_name":"Dobler"},{"first_name":"Emanuele","last_name":"Cacci","full_name":"Cacci, Emanuele"},{"first_name":"Johann G","last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G"},{"full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino"}],"related_material":{"record":[{"id":"9429","status":"public","relation":"later_version"},{"id":"8620","status":"public","relation":"dissertation_contains"}]},"date_created":"2020-05-05T14:31:33Z","date_updated":"2024-03-28T23:30:14Z"},{"page":"126-137","article_type":"original","citation":{"ama":"Basilico B, Morandell J, Novarino G. Molecular mechanisms for targeted ASD treatments. Current Opinion in Genetics and Development. 2020;65(12):126-137. doi:10.1016/j.gde.2020.06.004","apa":"Basilico, B., Morandell, J., & Novarino, G. (2020). Molecular mechanisms for targeted ASD treatments. Current Opinion in Genetics and Development. Elsevier. https://doi.org/10.1016/j.gde.2020.06.004","ieee":"B. Basilico, J. Morandell, and G. Novarino, “Molecular mechanisms for targeted ASD treatments,” Current Opinion in Genetics and Development, vol. 65, no. 12. Elsevier, pp. 126–137, 2020.","ista":"Basilico B, Morandell J, Novarino G. 2020. Molecular mechanisms for targeted ASD treatments. Current Opinion in Genetics and Development. 65(12), 126–137.","short":"B. Basilico, J. Morandell, G. Novarino, Current Opinion in Genetics and Development 65 (2020) 126–137.","mla":"Basilico, Bernadette, et al. “Molecular Mechanisms for Targeted ASD Treatments.” Current Opinion in Genetics and Development, vol. 65, no. 12, Elsevier, 2020, pp. 126–37, doi:10.1016/j.gde.2020.06.004.","chicago":"Basilico, Bernadette, Jasmin Morandell, and Gaia Novarino. “Molecular Mechanisms for Targeted ASD Treatments.” Current Opinion in Genetics and Development. Elsevier, 2020. https://doi.org/10.1016/j.gde.2020.06.004."},"publication":"Current Opinion in Genetics and Development","date_published":"2020-12-01T00:00:00Z","scopus_import":"1","has_accepted_license":"1","article_processing_charge":"Yes (via OA deal)","day":"01","intvolume":" 65","title":"Molecular mechanisms for targeted ASD treatments","ddc":["570"],"status":"public","_id":"8131","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","file":[{"file_size":1381545,"content_type":"application/pdf","creator":"dernst","file_name":"2020_CurrentOpGenetics_Basilico.pdf","access_level":"open_access","date_created":"2020-07-22T06:47:45Z","date_updated":"2020-07-22T06:47:45Z","success":1,"relation":"main_file","file_id":"8146"}],"oa_version":"Published Version","type":"journal_article","issue":"12","abstract":[{"lang":"eng","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."}],"project":[{"call_identifier":"H2020","name":"ISTplus - Postdoctoral Fellowships","_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411"},{"name":"Molecular Drug Targets","call_identifier":"FWF","grant_number":"W1232-B24","_id":"2548AE96-B435-11E9-9278-68D0E5697425"},{"name":"Neural stem cells in autism and epilepsy","grant_number":"F07807","_id":"05A0D778-7A3F-11EA-A408-12923DDC885E"}],"quality_controlled":"1","isi":1,"oa":1,"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"external_id":{"isi":["000598918900019"],"pmid":["32659636"]},"language":[{"iso":"eng"}],"doi":"10.1016/j.gde.2020.06.004","publication_identifier":{"issn":["0959437X"],"eissn":["18790380"]},"month":"12","publisher":"Elsevier","department":[{"_id":"GaNo"}],"publication_status":"published","pmid":1,"year":"2020","volume":65,"date_created":"2020-07-19T22:00:58Z","date_updated":"2024-03-28T23:30:14Z","related_material":{"record":[{"id":"8620","status":"public","relation":"dissertation_contains"}]},"author":[{"orcid":"0000-0003-1843-3173","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","last_name":"Basilico","first_name":"Bernadette","full_name":"Basilico, Bernadette"},{"full_name":"Morandell, Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","first_name":"Jasmin","last_name":"Morandell"},{"full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino"}],"ec_funded":1,"file_date_updated":"2020-07-22T06:47:45Z"},{"type":"journal_article","abstract":[{"lang":"eng","text":"Clinical Utility Gene Card. 1. Name of Disease (Synonyms): Pontocerebellar hypoplasia type 9 (PCH9) and spastic paraplegia-63 (SPG63). 2. OMIM# of the Disease: 615809 and 615686. 3. Name of the Analysed Genes or DNA/Chromosome Segments: AMPD2 at 1p13.3. 4. OMIM# of the Gene(s): 102771."}],"_id":"105","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","title":"CUGC for pontocerebellar hypoplasia type 9 and spastic paraplegia-63","status":"public","intvolume":" 27","oa_version":"Published Version","scopus_import":"1","day":"01","article_processing_charge":"No","publication":"European Journal of Human Genetics","citation":{"chicago":"Marsh, Ashley, Gaia Novarino, Paul Lockhart, and Richard Leventer. “CUGC for Pontocerebellar Hypoplasia Type 9 and Spastic Paraplegia-63.” European Journal of Human Genetics. Springer Nature, 2019. https://doi.org/10.1038/s41431-018-0231-2.","short":"A. Marsh, G. Novarino, P. Lockhart, R. Leventer, European Journal of Human Genetics 27 (2019) 161–166.","mla":"Marsh, Ashley, et al. “CUGC for Pontocerebellar Hypoplasia Type 9 and Spastic Paraplegia-63.” European Journal of Human Genetics, vol. 27, Springer Nature, 2019, pp. 161–66, doi:10.1038/s41431-018-0231-2.","ieee":"A. Marsh, G. Novarino, P. Lockhart, and R. Leventer, “CUGC for pontocerebellar hypoplasia type 9 and spastic paraplegia-63,” European Journal of Human Genetics, vol. 27. Springer Nature, pp. 161–166, 2019.","apa":"Marsh, A., Novarino, G., Lockhart, P., & Leventer, R. (2019). CUGC for pontocerebellar hypoplasia type 9 and spastic paraplegia-63. European Journal of Human Genetics. Springer Nature. https://doi.org/10.1038/s41431-018-0231-2","ista":"Marsh A, Novarino G, Lockhart P, Leventer R. 2019. CUGC for pontocerebellar hypoplasia type 9 and spastic paraplegia-63. European Journal of Human Genetics. 27, 161–166.","ama":"Marsh A, Novarino G, Lockhart P, Leventer R. CUGC for pontocerebellar hypoplasia type 9 and spastic paraplegia-63. European Journal of Human Genetics. 2019;27:161-166. doi:10.1038/s41431-018-0231-2"},"article_type":"original","page":"161-166","date_published":"2019-01-01T00:00:00Z","publist_id":"7949","year":"2019","acknowledgement":"This work was supported by EuroGentest2 (Unit 2: “Genetic testing as part of health care”), a Coordination Action under FP7 (Grant Agreement Number 261469) and the European Society of Human Genetics. We acknowledge the participation of the patients and their families in these studies, as well as the generous financial support of the Lefroy and Handbury families. APLM was supported by an Australian Postgraduate Award. PJL is supported by an NHMRC Career Development Fellowship (GNT1032364). RJL is supported by a Melbourne Children’s Clinician Scientist Fellowship.","pmid":1,"publication_status":"published","publisher":"Springer Nature","department":[{"_id":"GaNo"}],"author":[{"full_name":"Marsh, Ashley","first_name":"Ashley","last_name":"Marsh"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino","full_name":"Novarino, Gaia"},{"full_name":"Lockhart, Paul","first_name":"Paul","last_name":"Lockhart"},{"full_name":"Leventer, Richard","first_name":"Richard","last_name":"Leventer"}],"date_updated":"2023-08-24T14:28:24Z","date_created":"2018-12-11T11:44:39Z","volume":27,"month":"01","main_file_link":[{"url":"https://doi.org/10.1038/s41431-018-0231-2","open_access":"1"}],"external_id":{"isi":["000454111500019"],"pmid":["30089829"]},"oa":1,"quality_controlled":"1","isi":1,"doi":"10.1038/s41431-018-0231-2","language":[{"iso":"eng"}]},{"date_published":"2019-03-04T00:00:00Z","page":"1282-1293","citation":{"chicago":"Traxl, Alexander, Severin Mairinger, Thomas Filip, Michael Sauberer, Johann Stanek, Stefan Poschner, Walter Jäger, et al. “Inhibition of ABCB1 and ABCG2 at the Mouse Blood-Brain Barrier with Marketed Drugs to Improve Brain Delivery of the Model ABCB1/ABCG2 Substrate [11C]Erlotinib.” Molecular Pharmaceutics. American Chemical Society, 2019. https://doi.org/10.1021/acs.molpharmaceut.8b01217.","mla":"Traxl, Alexander, et al. “Inhibition of ABCB1 and ABCG2 at the Mouse Blood-Brain Barrier with Marketed Drugs to Improve Brain Delivery of the Model ABCB1/ABCG2 Substrate [11C]Erlotinib.” Molecular Pharmaceutics, vol. 16, no. 3, American Chemical Society, 2019, pp. 1282–93, doi:10.1021/acs.molpharmaceut.8b01217.","short":"A. Traxl, S. Mairinger, T. Filip, M. Sauberer, J. Stanek, S. Poschner, W. Jäger, V. Zoufal, G. Novarino, N. Tournier, M. Bauer, T. Wanek, O. Langer, Molecular Pharmaceutics 16 (2019) 1282–1293.","ista":"Traxl A, Mairinger S, Filip T, Sauberer M, Stanek J, Poschner S, Jäger W, Zoufal V, Novarino G, Tournier N, Bauer M, Wanek T, Langer O. 2019. Inhibition of ABCB1 and ABCG2 at the mouse blood-brain barrier with marketed drugs to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib. Molecular Pharmaceutics. 16(3), 1282–1293.","apa":"Traxl, A., Mairinger, S., Filip, T., Sauberer, M., Stanek, J., Poschner, S., … Langer, O. (2019). Inhibition of ABCB1 and ABCG2 at the mouse blood-brain barrier with marketed drugs to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib. Molecular Pharmaceutics. American Chemical Society. https://doi.org/10.1021/acs.molpharmaceut.8b01217","ieee":"A. Traxl et al., “Inhibition of ABCB1 and ABCG2 at the mouse blood-brain barrier with marketed drugs to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib,” Molecular Pharmaceutics, vol. 16, no. 3. American Chemical Society, pp. 1282–1293, 2019.","ama":"Traxl A, Mairinger S, Filip T, et al. Inhibition of ABCB1 and ABCG2 at the mouse blood-brain barrier with marketed drugs to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib. Molecular Pharmaceutics. 2019;16(3):1282-1293. doi:10.1021/acs.molpharmaceut.8b01217"},"publication":"Molecular Pharmaceutics","article_processing_charge":"No","day":"04","scopus_import":"1","oa_version":"None","intvolume":" 16","title":"Inhibition of ABCB1 and ABCG2 at the mouse blood-brain barrier with marketed drugs to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib","status":"public","_id":"6088","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","issue":"3","abstract":[{"lang":"eng","text":"P-Glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) are two efflux transporters at the blood–brain barrier (BBB), which effectively restrict brain distribution of diverse drugs, such as tyrosine kinase inhibitors. There is a crucial need for pharmacological ABCB1 and ABCG2 inhibition protocols for a more effective treatment of brain diseases. In the present study, seven marketed drugs (osimertinib, erlotinib, nilotinib, imatinib, lapatinib, pazopanib, and cyclosporine A) and one nonmarketed drug (tariquidar), with known in vitro ABCB1/ABCG2 inhibitory properties, were screened for their inhibitory potency at the BBB in vivo. Positron emission tomography (PET) using the model ABCB1/ABCG2 substrate [11C]erlotinib was performed in mice. Tested inhibitors were administered as i.v. bolus injections at 30 min before the start of the PET scan, followed by a continuous i.v. infusion for the duration of the PET scan. Five of the tested drugs increased total distribution volume of [11C]erlotinib in the brain (VT,brain) compared to vehicle-treated animals (tariquidar, + 69%; erlotinib, + 19% and +23% for the 21.5 mg/kg and the 43 mg/kg dose, respectively; imatinib, + 22%; lapatinib, + 25%; and cyclosporine A, + 49%). For all drugs, increases in [11C]erlotinib brain distribution were lower than in Abcb1a/b(−/−)Abcg2(−/−) mice (+149%), which suggested that only partial ABCB1/ABCG2 inhibition was reached at the mouse BBB. The plasma concentrations of the tested drugs at the time of the PET scan were higher than clinically achievable plasma concentrations. Some of the tested drugs led to significant increases in blood radioactivity concentrations measured at the end of the PET scan (erlotinib, + 103% and +113% for the 21.5 mg/kg and the 43 mg/kg dose, respectively; imatinib, + 125%; and cyclosporine A, + 101%), which was most likely caused by decreased hepatobiliary excretion of radioactivity. Taken together, our data suggest that some marketed tyrosine kinase inhibitors may be repurposed to inhibit ABCB1 and ABCG2 at the BBB. From a clinical perspective, moderate increases in brain delivery despite the administration of high i.v. doses as well as peripheral drug–drug interactions due to transporter inhibition in clearance organs question the translatability of this concept."}],"type":"journal_article","language":[{"iso":"eng"}],"doi":"10.1021/acs.molpharmaceut.8b01217","isi":1,"quality_controlled":"1","external_id":{"pmid":["30694684"],"isi":["000460600400031"]},"month":"03","volume":16,"date_created":"2019-03-10T22:59:19Z","date_updated":"2023-08-25T08:02:51Z","author":[{"first_name":"Alexander","last_name":"Traxl","full_name":"Traxl, Alexander"},{"last_name":"Mairinger","first_name":"Severin","full_name":"Mairinger, Severin"},{"last_name":"Filip","first_name":"Thomas","full_name":"Filip, Thomas"},{"first_name":"Michael","last_name":"Sauberer","full_name":"Sauberer, Michael"},{"first_name":"Johann","last_name":"Stanek","full_name":"Stanek, Johann"},{"first_name":"Stefan","last_name":"Poschner","full_name":"Poschner, Stefan"},{"first_name":"Walter","last_name":"Jäger","full_name":"Jäger, Walter"},{"last_name":"Zoufal","first_name":"Viktoria","full_name":"Zoufal, Viktoria"},{"last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia"},{"first_name":"Nicolas","last_name":"Tournier","full_name":"Tournier, Nicolas"},{"full_name":"Bauer, Martin","last_name":"Bauer","first_name":"Martin"},{"last_name":"Wanek","first_name":"Thomas","full_name":"Wanek, Thomas"},{"last_name":"Langer","first_name":"Oliver","full_name":"Langer, Oliver"}],"publisher":"American Chemical Society","department":[{"_id":"GaNo"}],"publication_status":"published","pmid":1,"year":"2019"},{"volume":1724,"date_updated":"2023-08-30T06:19:49Z","date_created":"2019-09-22T22:00:35Z","author":[{"id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","first_name":"Bárbara","last_name":"Oliveira","full_name":"Oliveira, Bárbara"},{"full_name":"Yahya, Aysan Çerağ","first_name":"Aysan Çerağ","last_name":"Yahya","id":"365A65F8-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia"}],"department":[{"_id":"GaNo"}],"publisher":"Elsevier","publication_status":"published","pmid":1,"year":"2019","article_number":"146458","language":[{"iso":"eng"}],"doi":"10.1016/j.brainres.2019.146458","quality_controlled":"1","isi":1,"external_id":{"isi":["000491646600033"],"pmid":["31521639"]},"publication_identifier":{"eissn":["18726240"],"issn":["00068993"]},"month":"12","oa_version":"None","intvolume":" 1724","status":"public","title":"Modeling cell-cell interactions in the brain using cerebral organoids","_id":"6896","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","abstract":[{"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.","lang":"eng"}],"type":"journal_article","date_published":"2019-12-01T00:00:00Z","article_type":"original","citation":{"chicago":"Oliveira, Bárbara, Aysan Çerağ Yahya, and Gaia Novarino. “Modeling Cell-Cell Interactions in the Brain Using Cerebral Organoids.” Brain Research. Elsevier, 2019. https://doi.org/10.1016/j.brainres.2019.146458.","mla":"Oliveira, Bárbara, et al. “Modeling Cell-Cell Interactions in the Brain Using Cerebral Organoids.” Brain Research, vol. 1724, 146458, Elsevier, 2019, doi:10.1016/j.brainres.2019.146458.","short":"B. Oliveira, A.Ç. Yahya, G. Novarino, Brain Research 1724 (2019).","ista":"Oliveira B, Yahya AÇ, Novarino G. 2019. Modeling cell-cell interactions in the brain using cerebral organoids. Brain Research. 1724, 146458.","apa":"Oliveira, B., Yahya, A. Ç., & Novarino, G. (2019). Modeling cell-cell interactions in the brain using cerebral organoids. Brain Research. Elsevier. https://doi.org/10.1016/j.brainres.2019.146458","ieee":"B. Oliveira, A. Ç. Yahya, and G. Novarino, “Modeling cell-cell interactions in the brain using cerebral organoids,” Brain Research, vol. 1724. Elsevier, 2019.","ama":"Oliveira B, Yahya AÇ, Novarino G. Modeling cell-cell interactions in the brain using cerebral organoids. Brain Research. 2019;1724. doi:10.1016/j.brainres.2019.146458"},"publication":"Brain Research","article_processing_charge":"No","day":"01","scopus_import":"1"},{"type":"journal_article","issue":"Supplement 6","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"7415","year":"2019","title":"S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism","publication_status":"published","status":"public","department":[{"_id":"GaNo"},{"_id":"LifeSc"}],"intvolume":" 29","publisher":"Elsevier","author":[{"full_name":"Morandell, Jasmin","last_name":"Morandell","first_name":"Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Nicolas, Armel","id":"2A103192-F248-11E8-B48F-1D18A9856A87","first_name":"Armel","last_name":"Nicolas"},{"full_name":"Schwarz, Lena A","id":"29A8453C-F248-11E8-B48F-1D18A9856A87","first_name":"Lena A","last_name":"Schwarz"},{"full_name":"Novarino, Gaia","last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"}],"date_updated":"2023-09-07T14:56:17Z","date_created":"2020-01-30T10:07:41Z","oa_version":"None","volume":29,"month":"12","day":"13","publication_identifier":{"issn":["0924-977X"]},"article_processing_charge":"No","publication":"European Neuropsychopharmacology","external_id":{"isi":["000502657500021"]},"citation":{"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.","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,” European Neuropsychopharmacology, vol. 29, no. Supplement 6. Elsevier, pp. S11–S12, 2019.","apa":"Morandell, J., Nicolas, A., Schwarz, L. A., & Novarino, G. (2019). S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism. European Neuropsychopharmacology. Elsevier. https://doi.org/10.1016/j.euroneuro.2019.09.040","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. European Neuropsychopharmacology. 2019;29(Supplement 6):S11-S12. doi:10.1016/j.euroneuro.2019.09.040","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.” European Neuropsychopharmacology. Elsevier, 2019. https://doi.org/10.1016/j.euroneuro.2019.09.040.","mla":"Morandell, Jasmin, et al. “S.16.05 Illuminating the Role of the E3 Ubiquitin Ligase Cullin3 in Brain Development and Autism.” European Neuropsychopharmacology, vol. 29, no. Supplement 6, Elsevier, 2019, pp. S11–12, doi:10.1016/j.euroneuro.2019.09.040.","short":"J. Morandell, A. Nicolas, L.A. Schwarz, G. Novarino, European Neuropsychopharmacology 29 (2019) S11–S12."},"article_type":"original","quality_controlled":"1","isi":1,"page":"S11-S12","date_published":"2019-12-13T00:00:00Z","doi":"10.1016/j.euroneuro.2019.09.040","language":[{"iso":"eng"}]},{"author":[{"full_name":"Knaus, Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","first_name":"Lisa","last_name":"Knaus"},{"id":"2ABCE612-F248-11E8-B48F-1D18A9856A87","last_name":"Tarlungeanu","first_name":"Dora-Clara","full_name":"Tarlungeanu, Dora-Clara"},{"full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia"}],"oa_version":"None","volume":29,"date_updated":"2023-09-07T14:55:23Z","date_created":"2020-01-30T10:06:15Z","_id":"7414","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","year":"2019","publisher":"Elsevier","department":[{"_id":"GaNo"}],"intvolume":" 29","title":"S.16.03 A homozygous missense mutation in SLC7A5 leads to autism spectrum disorder and microcephaly","status":"public","publication_status":"published","issue":"Supplement 6","type":"journal_article","doi":"10.1016/j.euroneuro.2019.09.039","date_published":"2019-12-13T00:00:00Z","language":[{"iso":"eng"}],"external_id":{"isi":["000502657500020"]},"citation":{"mla":"Knaus, Lisa, et al. “S.16.03 A Homozygous Missense Mutation in SLC7A5 Leads to Autism Spectrum Disorder and Microcephaly.” European Neuropsychopharmacology, vol. 29, no. Supplement 6, Elsevier, 2019, p. S11, doi:10.1016/j.euroneuro.2019.09.039.","short":"L. Knaus, D.-C. Tarlungeanu, G. Novarino, European Neuropsychopharmacology 29 (2019) S11.","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.” European Neuropsychopharmacology. Elsevier, 2019. https://doi.org/10.1016/j.euroneuro.2019.09.039.","ama":"Knaus L, Tarlungeanu D-C, Novarino G. S.16.03 A homozygous missense mutation in SLC7A5 leads to autism spectrum disorder and microcephaly. European Neuropsychopharmacology. 2019;29(Supplement 6):S11. doi:10.1016/j.euroneuro.2019.09.039","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.","apa":"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. Elsevier. https://doi.org/10.1016/j.euroneuro.2019.09.039","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,” European Neuropsychopharmacology, vol. 29, no. Supplement 6. Elsevier, p. S11, 2019."},"publication":"European Neuropsychopharmacology","page":"S11","isi":1,"quality_controlled":"1","article_type":"original","publication_identifier":{"issn":["0924-977X"]},"article_processing_charge":"No","day":"13","month":"12"},{"department":[{"_id":"GaNo"}],"publisher":"Institute of Science and Technology Austria","title":"Supplementary data for the research paper \"Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition\"","ddc":["570"],"status":"public","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"6074","year":"2019","oa_version":"Published Version","file":[{"checksum":"bc1b285edca9e98a2c63d153c79bb75b","date_updated":"2020-07-14T12:47:18Z","date_created":"2019-03-07T13:37:19Z","relation":"supplementary_material","file_id":"6084","content_type":"application/zip","file_size":33202743,"creator":"dernst","access_level":"open_access","file_name":"Setd5_paper.zip"}],"date_created":"2019-03-07T13:32:35Z","date_updated":"2024-02-21T13:41:01Z","related_material":{"record":[{"id":"3","relation":"research_paper","status":"public"}]},"author":[{"orcid":"0000-0002-9033-9096","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","last_name":"Dotter","first_name":"Christoph","full_name":"Dotter, Christoph"},{"full_name":"Novarino, Gaia","first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178"}],"type":"research_data","file_date_updated":"2020-07-14T12:47:18Z","abstract":[{"text":"This dataset contains the supplementary data for the research paper \"Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition\".\r\n\r\nThe contained files have the following content:\r\n'Supplementary Figures.pdf'\r\n\tAdditional figures (as referenced in the paper).\r\n'Supplementary Table 1. Statistics.xlsx'\r\n\tDetails on statistical tests performed in the paper.\r\n'Supplementary Table 2. Differentially expressed gene analysis.xlsx'\r\n\tResults for the differential gene expression analysis for embryonic (E9.5; analysis with edgeR) and in vitro (ESCs, EBs, NPCs; analysis with DESeq2) samples.\r\n'Supplementary Table 3. Gene Ontology (GO) term enrichment analysis.xlsx'\r\n\tResults for the GO term enrichment analysis for differentially expressed genes in embryonic (GO E9.5) and in vitro (GO ESC, GO EBs, GO NPCs) samples. Differentially expressed genes for in vitro samples were split into upregulated and downregulated genes (up/down) and the analysis was performed on each subset (e.g. GO ESC up / GO ESC down).\r\n'Supplementary Table 4. Differentially expressed gene analysis for CFC samples.xlsx'\r\n\tResults for the differential gene expression analysis for samples from adult mice before (HC - Homecage) and 1h and 3h after contextual fear conditioning (1h and 3h, respectively). Each sheet shows the results for a different comparison. Sheets 1-3 show results for comparisons between timepoints for wild type (WT) samples only and sheets 4-6 for the same comparisons in mutant (Het) samples. Sheets 7-9 show results for comparisons between genotypes at each time point and sheet 10 contains the results for the analysis of differential expression trajectories between wild type and mutant.\r\n'Supplementary Table 5. Cluster identification.xlsx'\r\n\tResults for k-means clustering of genes by expression. Sheet 1 shows clustering of just the genes with significantly different expression trajectories between genotypes. Sheet 2 shows clustering of all genes that are significantly differentially expressed in any of the comparisons (includes also genes with same trajectories).\r\n'Supplementary Table 6. GO term cluster analysis.xlsx'\r\n\tResults for the GO term enrichment analysis and EWCE analysis for enrichment of cell type specific genes for each cluster identified by clustering genes with different expression trajectories (see Table S5, sheet 1).\r\n'Supplementary Table 7. Setd5 mass spectrometry results.xlsx'\r\n\tResults showing proteins interacting with Setd5 as identified by mass spectrometry. Sheet 1 shows protein protein interaction data generated from these results (combined with data from the STRING database. Sheet 2 shows the results of the statistical analysis with limma.\r\n'Supplementary Table 8. PolII ChIP-seq analysis.xlsx'\r\n\tResults for the Chip-Seq analysis for binding of RNA polymerase II (PolII). Sheet 1 shows results for differential binding of PolII at the transcription start site (TSS) between genotypes and sheets 2+3 show the corresponding GO enrichment analysis for these differentially bound genes. Sheet 4 shows RNAseq counts for genes with increased binding of PolII at the TSS.","lang":"eng"}],"citation":{"chicago":"Dotter, Christoph, and Gaia Novarino. “Supplementary Data for the Research Paper ‘Haploinsufficiency of the Intellectual Disability Gene SETD5 Disturbs Developmental Gene Expression and Cognition.’” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6074.","mla":"Dotter, Christoph, and Gaia Novarino. Supplementary Data for the Research Paper “Haploinsufficiency of the Intellectual Disability Gene SETD5 Disturbs Developmental Gene Expression and Cognition.” Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6074.","short":"C. Dotter, G. Novarino, (2019).","ista":"Dotter C, Novarino G. 2019. Supplementary data for the research paper ‘Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition’, Institute of Science and Technology Austria, 10.15479/AT:ISTA:6074.","ieee":"C. Dotter and G. Novarino, “Supplementary data for the research paper ‘Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition.’” Institute of Science and Technology Austria, 2019.","apa":"Dotter, C., & Novarino, G. (2019). Supplementary data for the research paper “Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition.” Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6074","ama":"Dotter C, Novarino G. Supplementary data for the research paper “Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition.” 2019. doi:10.15479/AT:ISTA:6074"},"oa":1,"doi":"10.15479/AT:ISTA:6074","date_published":"2019-01-09T00:00:00Z","has_accepted_license":"1","article_processing_charge":"No","month":"01","day":"09"},{"intvolume":" 10","publisher":"American Association for the Advancement of Science","department":[{"_id":"GaNo"}],"status":"public","publication_status":"published","title":"Zika-associated microcephaly: Reduce the stress and race for the treatment","year":"2018","_id":"456","user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","oa_version":"None","volume":10,"date_updated":"2021-01-12T07:59:42Z","date_created":"2018-12-11T11:46:34Z","author":[{"full_name":"Novarino, Gaia","first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178"}],"type":"journal_article","article_number":"eaar7514","issue":"423","publist_id":"7365","abstract":[{"text":"Inhibition of the endoplasmic reticulum stress pathway may hold the key to Zika virus-associated microcephaly treatment. ","lang":"eng"}],"quality_controlled":"1","citation":{"chicago":"Novarino, Gaia. “Zika-Associated Microcephaly: Reduce the Stress and Race for the Treatment.” Science Translational Medicine. American Association for the Advancement of Science, 2018. https://doi.org/10.1126/scitranslmed.aar7514.","mla":"Novarino, Gaia. “Zika-Associated Microcephaly: Reduce the Stress and Race for the Treatment.” Science Translational Medicine, vol. 10, no. 423, eaar7514, American Association for the Advancement of Science, 2018, doi:10.1126/scitranslmed.aar7514.","short":"G. Novarino, Science Translational Medicine 10 (2018).","ista":"Novarino G. 2018. Zika-associated microcephaly: Reduce the stress and race for the treatment. Science Translational Medicine. 10(423), eaar7514.","apa":"Novarino, G. (2018). Zika-associated microcephaly: Reduce the stress and race for the treatment. Science Translational Medicine. American Association for the Advancement of Science. https://doi.org/10.1126/scitranslmed.aar7514","ieee":"G. Novarino, “Zika-associated microcephaly: Reduce the stress and race for the treatment,” Science Translational Medicine, vol. 10, no. 423. American Association for the Advancement of Science, 2018.","ama":"Novarino G. Zika-associated microcephaly: Reduce the stress and race for the treatment. Science Translational Medicine. 2018;10(423). doi:10.1126/scitranslmed.aar7514"},"publication":"Science Translational Medicine","language":[{"iso":"eng"}],"date_published":"2018-01-10T00:00:00Z","doi":"10.1126/scitranslmed.aar7514","scopus_import":1,"day":"10","month":"01"},{"file_date_updated":"2020-07-14T12:47:13Z","article_number":"100","volume":50,"date_updated":"2023-09-11T14:04:41Z","date_created":"2019-01-27T22:59:11Z","author":[{"full_name":"Tarlungeanu, Dora-Clara","id":"2ABCE612-F248-11E8-B48F-1D18A9856A87","first_name":"Dora-Clara","last_name":"Tarlungeanu"},{"last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia"}],"publisher":"Springer Nature","department":[{"_id":"GaNo"}],"publication_status":"published","pmid":1,"year":"2018","publication_identifier":{"issn":["2092-6413"]},"month":"08","language":[{"iso":"eng"}],"doi":"10.1038/s12276-018-0129-7","isi":1,"quality_controlled":"1","oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"pmid":["30089840"],"isi":["000441266700006"]},"issue":"8","abstract":[{"lang":"eng","text":"Despite the remarkable number of scientific breakthroughs of the last 100 years, the treatment of neurodevelopmental\r\ndisorders (e.g., autism spectrum disorder, intellectual disability) remains a great challenge. Recent advancements in\r\ngenomics, such as whole-exome or whole-genome sequencing, have enabled scientists to identify numerous\r\nmutations underlying neurodevelopmental disorders. Given the few hundred risk genes that have been discovered,\r\nthe etiological variability and the heterogeneous clinical presentation, the need for genotype — along with phenotype-\r\nbased diagnosis of individual patients has become a requisite. In this review we look at recent advancements in\r\ngenomic analysis and their translation into clinical practice."}],"type":"journal_article","file":[{"access_level":"open_access","file_name":"2018_EMM_Tarlungeanu.pdf","creator":"dernst","file_size":1237482,"content_type":"application/pdf","file_id":"5893","relation":"main_file","checksum":"4498301c8c53097c9a1a8ef990936eb5","date_updated":"2020-07-14T12:47:13Z","date_created":"2019-01-28T15:18:02Z"}],"oa_version":"Published Version","intvolume":" 50","ddc":["570"],"title":"Genomics in neurodevelopmental disorders: an avenue to personalized medicine","status":"public","_id":"5888","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","has_accepted_license":"1","article_processing_charge":"No","day":"07","scopus_import":"1","date_published":"2018-08-07T00:00:00Z","citation":{"chicago":"Tarlungeanu, Dora-Clara, and Gaia Novarino. “Genomics in Neurodevelopmental Disorders: An Avenue to Personalized Medicine.” Experimental & Molecular Medicine. Springer Nature, 2018. https://doi.org/10.1038/s12276-018-0129-7.","mla":"Tarlungeanu, Dora-Clara, and Gaia Novarino. “Genomics in Neurodevelopmental Disorders: An Avenue to Personalized Medicine.” Experimental & Molecular Medicine, vol. 50, no. 8, 100, Springer Nature, 2018, doi:10.1038/s12276-018-0129-7.","short":"D.-C. Tarlungeanu, G. Novarino, Experimental & Molecular Medicine 50 (2018).","ista":"Tarlungeanu D-C, Novarino G. 2018. Genomics in neurodevelopmental disorders: an avenue to personalized medicine. Experimental & Molecular Medicine. 50(8), 100.","ieee":"D.-C. Tarlungeanu and G. Novarino, “Genomics in neurodevelopmental disorders: an avenue to personalized medicine,” Experimental & Molecular Medicine, vol. 50, no. 8. Springer Nature, 2018.","apa":"Tarlungeanu, D.-C., & Novarino, G. (2018). Genomics in neurodevelopmental disorders: an avenue to personalized medicine. Experimental & Molecular Medicine. Springer Nature. https://doi.org/10.1038/s12276-018-0129-7","ama":"Tarlungeanu D-C, Novarino G. Genomics in neurodevelopmental disorders: an avenue to personalized medicine. Experimental & Molecular Medicine. 2018;50(8). doi:10.1038/s12276-018-0129-7"},"publication":"Experimental & Molecular Medicine"},{"scopus_import":"1","day":"01","article_processing_charge":"No","publication":"Current Opinion in Neurobiology","citation":{"ama":"Sacco R, Cacci E, Novarino G. Neural stem cells in neuropsychiatric disorders. Current Opinion in Neurobiology. 2018;48(2):131-138. doi:10.1016/j.conb.2017.12.005","ista":"Sacco R, Cacci E, Novarino G. 2018. Neural stem cells in neuropsychiatric disorders. Current Opinion in Neurobiology. 48(2), 131–138.","ieee":"R. Sacco, E. Cacci, and G. Novarino, “Neural stem cells in neuropsychiatric disorders,” Current Opinion in Neurobiology, vol. 48, no. 2. Elsevier, pp. 131–138, 2018.","apa":"Sacco, R., Cacci, E., & Novarino, G. (2018). Neural stem cells in neuropsychiatric disorders. Current Opinion in Neurobiology. Elsevier. https://doi.org/10.1016/j.conb.2017.12.005","mla":"Sacco, Roberto, et al. “Neural Stem Cells in Neuropsychiatric Disorders.” Current Opinion in Neurobiology, vol. 48, no. 2, Elsevier, 2018, pp. 131–38, doi:10.1016/j.conb.2017.12.005.","short":"R. Sacco, E. Cacci, G. Novarino, Current Opinion in Neurobiology 48 (2018) 131–138.","chicago":"Sacco, Roberto, Emanuele Cacci, and Gaia Novarino. “Neural Stem Cells in Neuropsychiatric Disorders.” Current Opinion in Neurobiology. Elsevier, 2018. https://doi.org/10.1016/j.conb.2017.12.005."},"page":"131 - 138","date_published":"2018-02-01T00:00:00Z","type":"journal_article","abstract":[{"lang":"eng","text":"The precise control of neural stem cell (NSC) proliferation and differentiation is crucial for the development and function of the human brain. Here, we review the emerging links between the alteration of embryonic and adult neurogenesis and the etiology of neuropsychiatric disorders (NPDs) such as autism spectrum disorders (ASDs) and schizophrenia (SCZ), as well as the advances in stem cell-based modeling and the novel therapeutic targets derived from these studies."}],"issue":"2","_id":"546","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","title":"Neural stem cells in neuropsychiatric disorders","status":"public","intvolume":" 48","oa_version":"None","month":"02","external_id":{"isi":["000427101600018"]},"quality_controlled":"1","isi":1,"doi":"10.1016/j.conb.2017.12.005","language":[{"iso":"eng"}],"publist_id":"7268","year":"2018","publication_status":"published","department":[{"_id":"GaNo"}],"publisher":"Elsevier","author":[{"last_name":"Sacco","first_name":"Roberto","id":"42C9F57E-F248-11E8-B48F-1D18A9856A87","full_name":"Sacco, Roberto"},{"full_name":"Cacci, Emanuele","last_name":"Cacci","first_name":"Emanuele"},{"orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia","full_name":"Novarino, Gaia"}],"date_updated":"2023-09-13T09:01:56Z","date_created":"2018-12-11T11:47:06Z","volume":48},{"type":"journal_article","issue":"1","abstract":[{"text":"Background: Transport protein particle (TRAPP) is a multisubunit complex that regulates membrane trafficking through the Golgi apparatus. The clinical phenotype associated with mutations in various TRAPP subunits has allowed elucidation of their functions in specific tissues. The role of some subunits in human disease, however, has not been fully established, and their functions remain uncertain.\r\n\r\nObjective: We aimed to expand the range of neurodevelopmental disorders associated with mutations in TRAPP subunits by exome sequencing of consanguineous families.\r\n\r\nMethods: Linkage and homozygosity mapping and candidate gene analysis were used to identify homozygous mutations in families. Patient fibroblasts were used to study splicing defect and zebrafish to model the disease.\r\n\r\nResults: We identified six individuals from three unrelated families with a founder homozygous splice mutation in TRAPPC6B, encoding a core subunit of the complex TRAPP I. Patients manifested a neurodevelopmental disorder characterised by microcephaly, epilepsy and autistic features, and showed splicing defect. Zebrafish trappc6b morphants replicated the human phenotype, displaying decreased head size and neuronal hyperexcitability, leading to a lower seizure threshold.\r\n\r\nConclusion: This study provides clinical and functional evidence of the role of TRAPPC6B in brain development and function.","lang":"eng"}],"intvolume":" 55","status":"public","title":"A homozygous founder mutation in TRAPPC6B associates with a neurodevelopmental disorder characterised by microcephaly epilepsy and autistic features","_id":"691","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa_version":"Submitted Version","scopus_import":"1","article_processing_charge":"No","day":"01","page":"48 - 54","article_type":"original","citation":{"chicago":"Marin Valencia, Isaac, Gaia Novarino, Anide Johansen, Başak Rosti, Mahmoud Issa, Damir Musaev, Gifty Bhat, et al. “A Homozygous Founder Mutation in TRAPPC6B Associates with a Neurodevelopmental Disorder Characterised by Microcephaly Epilepsy and Autistic Features.” Journal of Medical Genetics. BMJ Publishing Group, 2018. https://doi.org/10.1136/jmedgenet-2017-104627.","mla":"Marin Valencia, Isaac, et al. “A Homozygous Founder Mutation in TRAPPC6B Associates with a Neurodevelopmental Disorder Characterised by Microcephaly Epilepsy and Autistic Features.” Journal of Medical Genetics, vol. 55, no. 1, BMJ Publishing Group, 2018, pp. 48–54, doi:10.1136/jmedgenet-2017-104627.","short":"I. Marin Valencia, G. Novarino, A. Johansen, B. Rosti, M. Issa, D. Musaev, G. Bhat, E. Scott, J. Silhavy, V. Stanley, R. Rosti, J. Gleeson, F. Imam, M. Zaki, J. Gleeson, Journal of Medical Genetics 55 (2018) 48–54.","ista":"Marin Valencia I, Novarino G, Johansen A, Rosti B, Issa M, Musaev D, Bhat G, Scott E, Silhavy J, Stanley V, Rosti R, Gleeson J, Imam F, Zaki M, Gleeson J. 2018. A homozygous founder mutation in TRAPPC6B associates with a neurodevelopmental disorder characterised by microcephaly epilepsy and autistic features. Journal of Medical Genetics. 55(1), 48–54.","apa":"Marin Valencia, I., Novarino, G., Johansen, A., Rosti, B., Issa, M., Musaev, D., … Gleeson, J. (2018). A homozygous founder mutation in TRAPPC6B associates with a neurodevelopmental disorder characterised by microcephaly epilepsy and autistic features. Journal of Medical Genetics. BMJ Publishing Group. https://doi.org/10.1136/jmedgenet-2017-104627","ieee":"I. Marin Valencia et al., “A homozygous founder mutation in TRAPPC6B associates with a neurodevelopmental disorder characterised by microcephaly epilepsy and autistic features,” Journal of Medical Genetics, vol. 55, no. 1. BMJ Publishing Group, pp. 48–54, 2018.","ama":"Marin Valencia I, Novarino G, Johansen A, et al. A homozygous founder mutation in TRAPPC6B associates with a neurodevelopmental disorder characterised by microcephaly epilepsy and autistic features. Journal of Medical Genetics. 2018;55(1):48-54. doi:10.1136/jmedgenet-2017-104627"},"publication":"Journal of Medical Genetics","date_published":"2018-01-01T00:00:00Z","publist_id":"7016","department":[{"_id":"GaNo"}],"publisher":"BMJ Publishing Group","publication_status":"published","pmid":1,"year":"2018","volume":55,"date_updated":"2023-10-16T09:55:43Z","date_created":"2018-12-11T11:47:57Z","author":[{"first_name":"Isaac","last_name":"Marin Valencia","full_name":"Marin Valencia, Isaac"},{"full_name":"Novarino, Gaia","first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178"},{"first_name":"Anide","last_name":"Johansen","full_name":"Johansen, Anide"},{"first_name":"Başak","last_name":"Rosti","full_name":"Rosti, Başak"},{"full_name":"Issa, Mahmoud","first_name":"Mahmoud","last_name":"Issa"},{"first_name":"Damir","last_name":"Musaev","full_name":"Musaev, Damir"},{"last_name":"Bhat","first_name":"Gifty","full_name":"Bhat, Gifty"},{"first_name":"Eric","last_name":"Scott","full_name":"Scott, Eric"},{"full_name":"Silhavy, Jennifer","first_name":"Jennifer","last_name":"Silhavy"},{"full_name":"Stanley, Valentina","last_name":"Stanley","first_name":"Valentina"},{"full_name":"Rosti, Rasim","first_name":"Rasim","last_name":"Rosti"},{"first_name":"Jeremy","last_name":"Gleeson","full_name":"Gleeson, Jeremy"},{"full_name":"Imam, Farhad","first_name":"Farhad","last_name":"Imam"},{"full_name":"Zaki, Maha","last_name":"Zaki","first_name":"Maha"},{"last_name":"Gleeson","first_name":"Joseph","full_name":"Gleeson, Joseph"}],"publication_identifier":{"issn":["0022-2593"]},"month":"01","project":[{"name":"Probing development and reversibility of autism spectrum disorders","_id":"254BA948-B435-11E9-9278-68D0E5697425","grant_number":"401299"}],"quality_controlled":"1","isi":1,"main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056005/","open_access":"1"}],"oa":1,"external_id":{"pmid":["28626029"],"isi":["000418199800007"]},"language":[{"iso":"eng"}],"doi":"10.1136/jmedgenet-2017-104627"},{"acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"PreCl"}],"language":[{"iso":"eng"}],"doi":"10.1038/s41593-018-0266-2","isi":1,"quality_controlled":"1","project":[{"grant_number":"401299","_id":"254BA948-B435-11E9-9278-68D0E5697425","name":"Probing development and reversibility of autism spectrum disorders"}],"external_id":{"isi":["000451324700010"]},"oa":1,"month":"11","date_created":"2018-12-11T11:44:05Z","date_updated":"2024-03-28T23:30:45Z","volume":21,"author":[{"last_name":"Deliu","first_name":"Elena","orcid":"0000-0002-7370-5293","id":"37A40D7E-F248-11E8-B48F-1D18A9856A87","full_name":"Deliu, Elena"},{"last_name":"Arecco","first_name":"Niccoló","full_name":"Arecco, Niccoló"},{"id":"4739D480-F248-11E8-B48F-1D18A9856A87","last_name":"Morandell","first_name":"Jasmin","full_name":"Morandell, Jasmin"},{"full_name":"Dotter, Christoph","first_name":"Christoph","last_name":"Dotter","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9033-9096"},{"full_name":"Contreras, Ximena","id":"475990FE-F248-11E8-B48F-1D18A9856A87","last_name":"Contreras","first_name":"Ximena"},{"full_name":"Girardot, Charles","first_name":"Charles","last_name":"Girardot"},{"first_name":"Eva","last_name":"Käsper","full_name":"Käsper, Eva"},{"first_name":"Alena","last_name":"Kozlova","id":"C50A9596-02D0-11E9-976E-E38CFE5CBC1D","full_name":"Kozlova, Alena"},{"full_name":"Kishi, Kasumi","last_name":"Kishi","first_name":"Kasumi","id":"3065DFC4-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Chiaradia, Ilaria","last_name":"Chiaradia","first_name":"Ilaria","orcid":"0000-0002-9529-4464","id":"B6467F20-02D0-11E9-BDA5-E960C241894A"},{"full_name":"Noh, Kyung","first_name":"Kyung","last_name":"Noh"},{"first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"}],"related_material":{"link":[{"description":"News on IST Homepage","relation":"press_release","url":"https://ist.ac.at/en/news/mutation-that-causes-autism-and-intellectual-disability-makes-brain-less-flexible/"}],"record":[{"id":"6074","status":"public","relation":"popular_science"},{"id":"12364","status":"public","relation":"dissertation_contains"}]},"publication_status":"published","department":[{"_id":"GaNo"},{"_id":"EdHa"}],"publisher":"Nature Publishing Group","year":"2018","acknowledgement":"This work was supported by the Simons Foundation Autism Research Initiative (grant 401299) to G.N. and the DFG (SPP1738 grant NO 1249) to K.-M.N.","file_date_updated":"2020-07-14T12:45:58Z","publist_id":"8054","date_published":"2018-11-19T00:00:00Z","article_type":"original","page":"1717 - 1727","publication":"Nature Neuroscience","citation":{"ista":"Deliu E, Arecco N, Morandell J, Dotter C, Contreras X, Girardot C, Käsper E, Kozlova A, Kishi K, Chiaradia I, Noh K, Novarino G. 2018. Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition. Nature Neuroscience. 21(12), 1717–1727.","ieee":"E. Deliu et al., “Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition,” Nature Neuroscience, vol. 21, no. 12. Nature Publishing Group, pp. 1717–1727, 2018.","apa":"Deliu, E., Arecco, N., Morandell, J., Dotter, C., Contreras, X., Girardot, C., … Novarino, G. (2018). Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition. Nature Neuroscience. Nature Publishing Group. https://doi.org/10.1038/s41593-018-0266-2","ama":"Deliu E, Arecco N, Morandell J, et al. Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition. Nature Neuroscience. 2018;21(12):1717-1727. doi:10.1038/s41593-018-0266-2","chicago":"Deliu, Elena, Niccoló Arecco, Jasmin Morandell, Christoph Dotter, Ximena Contreras, Charles Girardot, Eva Käsper, et al. “Haploinsufficiency of the Intellectual Disability Gene SETD5 Disturbs Developmental Gene Expression and Cognition.” Nature Neuroscience. Nature Publishing Group, 2018. https://doi.org/10.1038/s41593-018-0266-2.","mla":"Deliu, Elena, et al. “Haploinsufficiency of the Intellectual Disability Gene SETD5 Disturbs Developmental Gene Expression and Cognition.” Nature Neuroscience, vol. 21, no. 12, Nature Publishing Group, 2018, pp. 1717–27, doi:10.1038/s41593-018-0266-2.","short":"E. Deliu, N. Arecco, J. Morandell, C. Dotter, X. Contreras, C. Girardot, E. Käsper, A. Kozlova, K. Kishi, I. Chiaradia, K. Noh, G. Novarino, Nature Neuroscience 21 (2018) 1717–1727."},"day":"19","article_processing_charge":"No","has_accepted_license":"1","scopus_import":"1","oa_version":"Submitted Version","file":[{"file_name":"2017_NatureNeuroscience_Deliu.pdf","access_level":"open_access","content_type":"application/pdf","file_size":8167169,"creator":"dernst","relation":"main_file","file_id":"6255","date_created":"2019-04-09T07:41:57Z","date_updated":"2020-07-14T12:45:58Z","checksum":"60abd0f05b7cdc08a6b0ec460884084f"}],"pubrep_id":"1071","title":"Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition","status":"public","ddc":["570"],"intvolume":" 21","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"3","abstract":[{"text":"SETD5 gene mutations have been identified as a frequent cause of idiopathic intellectual disability. Here we show that Setd5-haploinsufficient mice present developmental defects such as abnormal brain-to-body weight ratios and neural crest defect-associated phenotypes. Furthermore, Setd5-mutant mice show impairments in cognitive tasks, enhanced long-term potentiation, delayed ontogenetic profile of ultrasonic vocalization, and behavioral inflexibility. Behavioral issues are accompanied by abnormal expression of postsynaptic density proteins previously associated with cognition. Our data additionally indicate that Setd5 regulates RNA polymerase II dynamics and gene transcription via its interaction with the Hdac3 and Paf1 complexes, findings potentially explaining the gene expression defects observed in Setd5-haploinsufficient mice. Our results emphasize the decisive role of Setd5 in a biological pathway found to be disrupted in humans with intellectual disability and autism spectrum disorder.","lang":"eng"}],"issue":"12","type":"journal_article"},{"abstract":[{"lang":"eng","text":"Genetic factors might be largely responsible for the development of autism spectrum disorder (ASD) that alone or in combination with specific environmental risk factors trigger the pathology. Multiple mutations identified in ASD patients that impair synaptic function in the central nervous system are well studied in animal models. How these mutations might interact with other risk factors is not fully understood though. Additionally, how systems outside of the brain are altered in the context of ASD is an emerging area of research. Extracerebral influences on the physiology could begin in utero and contribute to changes in the brain and in the development of other body systems and further lead to epigenetic changes. Therefore, multiple recent studies have aimed at elucidating the role of gene-environment interactions in ASD. Here we provide an overview on the extracerebral systems that might play an important associative role in ASD and review evidence regarding the potential roles of inflammation, trace metals, metabolism, genetic susceptibility, enteric nervous system function and the microbiota of the gastrointestinal (GI) tract on the development of endophenotypes in animal models of ASD. By influencing environmental conditions, it might be possible to reduce or limit the severity of ASD pathology."}],"alternative_title":["ADVSANAT"],"type":"book_chapter","oa_version":"None","title":"Extracerebral dysfunction in animal models of autism spectrum disorder","status":"public","intvolume":" 224","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"623","day":"28","series_title":"Advances in Anatomy Embryology and Cell Biology","scopus_import":1,"date_published":"2017-05-28T00:00:00Z","page":"159 - 187","publication":"Translational Anatomy and Cell Biology of Autism Spectrum Disorder","citation":{"ista":"Hill Yardin E, Mckeown S, Novarino G, Grabrucker A. 2017.Extracerebral dysfunction in animal models of autism spectrum disorder. In: Translational Anatomy and Cell Biology of Autism Spectrum Disorder. ADVSANAT, vol. 224, 159–187.","ieee":"E. Hill Yardin, S. Mckeown, G. Novarino, and A. Grabrucker, “Extracerebral dysfunction in animal models of autism spectrum disorder,” in Translational Anatomy and Cell Biology of Autism Spectrum Disorder, vol. 224, M. Schmeisser and T. Boekers, Eds. Springer, 2017, pp. 159–187.","apa":"Hill Yardin, E., Mckeown, S., Novarino, G., & Grabrucker, A. (2017). Extracerebral dysfunction in animal models of autism spectrum disorder. In M. Schmeisser & T. Boekers (Eds.), Translational Anatomy and Cell Biology of Autism Spectrum Disorder (Vol. 224, pp. 159–187). Springer. https://doi.org/10.1007/978-3-319-52498-6_9","ama":"Hill Yardin E, Mckeown S, Novarino G, Grabrucker A. Extracerebral dysfunction in animal models of autism spectrum disorder. In: Schmeisser M, Boekers T, eds. Translational Anatomy and Cell Biology of Autism Spectrum Disorder. Vol 224. Advances in Anatomy Embryology and Cell Biology. Springer; 2017:159-187. doi:10.1007/978-3-319-52498-6_9","chicago":"Hill Yardin, Elisa, Sonja Mckeown, Gaia Novarino, and Andreas Grabrucker. “Extracerebral Dysfunction in Animal Models of Autism Spectrum Disorder.” In Translational Anatomy and Cell Biology of Autism Spectrum Disorder, edited by Michael Schmeisser and Tobias Boekers, 224:159–87. Advances in Anatomy Embryology and Cell Biology. Springer, 2017. https://doi.org/10.1007/978-3-319-52498-6_9.","mla":"Hill Yardin, Elisa, et al. “Extracerebral Dysfunction in Animal Models of Autism Spectrum Disorder.” Translational Anatomy and Cell Biology of Autism Spectrum Disorder, edited by Michael Schmeisser and Tobias Boekers, vol. 224, Springer, 2017, pp. 159–87, doi:10.1007/978-3-319-52498-6_9.","short":"E. Hill Yardin, S. Mckeown, G. Novarino, A. Grabrucker, in:, M. Schmeisser, T. Boekers (Eds.), Translational Anatomy and Cell Biology of Autism Spectrum Disorder, Springer, 2017, pp. 159–187."},"publist_id":"7177","date_updated":"2021-01-12T08:06:46Z","date_created":"2018-12-11T11:47:33Z","volume":224,"author":[{"full_name":"Hill Yardin, Elisa","first_name":"Elisa","last_name":"Hill Yardin"},{"full_name":"Mckeown, Sonja","last_name":"Mckeown","first_name":"Sonja"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino","full_name":"Novarino, Gaia"},{"last_name":"Grabrucker","first_name":"Andreas","full_name":"Grabrucker, Andreas"}],"publication_status":"published","editor":[{"full_name":"Schmeisser, Michael","last_name":"Schmeisser","first_name":"Michael"},{"full_name":"Boekers, Tobias","first_name":"Tobias","last_name":"Boekers"}],"department":[{"_id":"GaNo"}],"publisher":"Springer","year":"2017","month":"05","publication_identifier":{"issn":["03015556"],"isbn":["978-3-319-52496-2"]},"language":[{"iso":"eng"}],"doi":"10.1007/978-3-319-52498-6_9","quality_controlled":"1"},{"date_published":"2017-05-28T00:00:00Z","publication":"Translational Anatomy and Cell Biology of Autism Spectrum Disorder","citation":{"chicago":"Schroeder, Jan, Elena Deliu, Gaia Novarino, and Michael Schmeisser. “Genetic and Pharmacological Reversibility of Phenotypes in Mouse Models of Autism Spectrum Disorder.” In Translational Anatomy and Cell Biology of Autism Spectrum Disorder, edited by Michael Schmeisser and Tobias Boekers, 224:189–211. Advances in Anatomy Embryology and Cell Biology. Springer, 2017. https://doi.org/10.1007/978-3-319-52498-6_10.","short":"J. Schroeder, E. Deliu, G. Novarino, M. Schmeisser, in:, M. Schmeisser, T. Boekers (Eds.), Translational Anatomy and Cell Biology of Autism Spectrum Disorder, Springer, 2017, pp. 189–211.","mla":"Schroeder, Jan, et al. “Genetic and Pharmacological Reversibility of Phenotypes in Mouse Models of Autism Spectrum Disorder.” Translational Anatomy and Cell Biology of Autism Spectrum Disorder, edited by Michael Schmeisser and Tobias Boekers, vol. 224, Springer, 2017, pp. 189–211, doi:10.1007/978-3-319-52498-6_10.","ieee":"J. Schroeder, E. Deliu, G. Novarino, and M. Schmeisser, “Genetic and pharmacological reversibility of phenotypes in mouse models of autism spectrum disorder,” in Translational Anatomy and Cell Biology of Autism Spectrum Disorder, vol. 224, M. Schmeisser and T. Boekers, Eds. Springer, 2017, pp. 189–211.","apa":"Schroeder, J., Deliu, E., Novarino, G., & Schmeisser, M. (2017). Genetic and pharmacological reversibility of phenotypes in mouse models of autism spectrum disorder. In M. Schmeisser & T. Boekers (Eds.), Translational Anatomy and Cell Biology of Autism Spectrum Disorder (Vol. 224, pp. 189–211). Springer. https://doi.org/10.1007/978-3-319-52498-6_10","ista":"Schroeder J, Deliu E, Novarino G, Schmeisser M. 2017.Genetic and pharmacological reversibility of phenotypes in mouse models of autism spectrum disorder. In: Translational Anatomy and Cell Biology of Autism Spectrum Disorder. ADVSANAT, vol. 224, 189–211.","ama":"Schroeder J, Deliu E, Novarino G, Schmeisser M. Genetic and pharmacological reversibility of phenotypes in mouse models of autism spectrum disorder. In: Schmeisser M, Boekers T, eds. Translational Anatomy and Cell Biology of Autism Spectrum Disorder. Vol 224. Advances in Anatomy Embryology and Cell Biology. Springer; 2017:189-211. doi:10.1007/978-3-319-52498-6_10"},"page":"189 - 211","day":"28","scopus_import":1,"series_title":"Advances in Anatomy Embryology and Cell Biology","oa_version":"None","_id":"634","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","title":"Genetic and pharmacological reversibility of phenotypes in mouse models of autism spectrum disorder","status":"public","intvolume":" 224","abstract":[{"lang":"eng","text":"As autism spectrum disorder (ASD) is largely regarded as a neurodevelopmental condition, long-time consensus was that its hallmark features are irreversible. However, several studies from recent years using defined mouse models of ASD have provided clear evidence that in mice neurobiological and behavioural alterations can be ameliorated or even reversed by genetic restoration or pharmacological treatment either before or after symptom onset. Here, we review findings on genetic and pharmacological reversibility of phenotypes in mouse models of ASD. Our review should give a comprehensive overview on both aspects and encourage future studies to better understand the underlying molecular mechanisms that might be translatable from animals to humans."}],"type":"book_chapter","alternative_title":["ADVSANAT"],"doi":"10.1007/978-3-319-52498-6_10","language":[{"iso":"eng"}],"quality_controlled":"1","project":[{"name":"Transmembrane Transporters in Health and Disease","call_identifier":"FWF","_id":"25473368-B435-11E9-9278-68D0E5697425","grant_number":"F03523"}],"month":"05","publication_identifier":{"eisbn":["978-3-319-52498-6"]},"author":[{"last_name":"Schroeder","first_name":"Jan","full_name":"Schroeder, Jan"},{"last_name":"Deliu","first_name":"Elena","orcid":"0000-0002-7370-5293","id":"37A40D7E-F248-11E8-B48F-1D18A9856A87","full_name":"Deliu, Elena"},{"last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia"},{"first_name":"Michael","last_name":"Schmeisser","full_name":"Schmeisser, Michael"}],"date_updated":"2021-01-12T08:07:08Z","date_created":"2018-12-11T11:47:37Z","volume":224,"year":"2017","publication_status":"published","publisher":"Springer","department":[{"_id":"GaNo"}],"editor":[{"last_name":"Schmeisser","first_name":"Michael","full_name":"Schmeisser, Michael"},{"full_name":"Boekers, Tobias","first_name":"Tobias","last_name":"Boekers"}],"publist_id":"7156"},{"scopus_import":1,"month":"03","day":"15","publication_identifier":{"issn":["19466234"]},"quality_controlled":"1","publication":"Science Translational Medicine","citation":{"ista":"Novarino G. 2017. Modeling Alzheimer’s disease in mice with human neurons. Science Translational Medicine. 9(381), eaam9867.","apa":"Novarino, G. (2017). Modeling Alzheimer’s disease in mice with human neurons. Science Translational Medicine. American Association for the Advancement of Science. https://doi.org/10.1126/scitranslmed.aam9867","ieee":"G. Novarino, “Modeling Alzheimer’s disease in mice with human neurons,” Science Translational Medicine, vol. 9, no. 381. American Association for the Advancement of Science, 2017.","ama":"Novarino G. Modeling Alzheimer’s disease in mice with human neurons. Science Translational Medicine. 2017;9(381). doi:10.1126/scitranslmed.aam9867","chicago":"Novarino, Gaia. “Modeling Alzheimer’s Disease in Mice with Human Neurons.” Science Translational Medicine. American Association for the Advancement of Science, 2017. https://doi.org/10.1126/scitranslmed.aam9867.","mla":"Novarino, Gaia. “Modeling Alzheimer’s Disease in Mice with Human Neurons.” Science Translational Medicine, vol. 9, no. 381, eaam9867, American Association for the Advancement of Science, 2017, doi:10.1126/scitranslmed.aam9867.","short":"G. Novarino, Science Translational Medicine 9 (2017)."},"language":[{"iso":"eng"}],"doi":"10.1126/scitranslmed.aam9867","date_published":"2017-03-15T00:00:00Z","article_number":"eaam9867","type":"journal_article","abstract":[{"lang":"eng","text":"Human neurons transplanted into a mouse model for Alzheimer’s disease show human-specific vulnerability to β-amyloid plaques and may help to identify new therapeutic targets."}],"publist_id":"7079","issue":"381","status":"public","publication_status":"published","title":"Modeling Alzheimer's disease in mice with human neurons","intvolume":" 9","publisher":"American Association for the Advancement of Science","department":[{"_id":"GaNo"}],"year":"2017","_id":"656","user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","date_created":"2018-12-11T11:47:45Z","date_updated":"2021-01-12T08:07:59Z","oa_version":"None","volume":9,"author":[{"full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino"}]},{"publist_id":"7060","issue":"387","abstract":[{"text":"Perinatal exposure to penicillin may result in longlasting gut and behavioral changes.","lang":"eng"}],"type":"journal_article","article_number":"2786","author":[{"full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino"}],"volume":9,"oa_version":"None","date_created":"2018-12-11T11:47:48Z","date_updated":"2021-01-12T08:08:30Z","_id":"667","user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","year":"2017","intvolume":" 9","department":[{"_id":"GaNo"}],"publisher":"American Association for the Advancement of Science","title":"The antisocial side of antibiotics","status":"public","publication_status":"published","publication_identifier":{"issn":["19466234"]},"day":"26","month":"04","scopus_import":1,"date_published":"2017-04-26T00:00:00Z","doi":"10.1126/scitranslmed.aan2786","language":[{"iso":"eng"}],"citation":{"ama":"Novarino G. The antisocial side of antibiotics. Science Translational Medicine. 2017;9(387). doi:10.1126/scitranslmed.aan2786","ieee":"G. Novarino, “The antisocial side of antibiotics,” Science Translational Medicine, vol. 9, no. 387. American Association for the Advancement of Science, 2017.","apa":"Novarino, G. (2017). The antisocial side of antibiotics. Science Translational Medicine. American Association for the Advancement of Science. https://doi.org/10.1126/scitranslmed.aan2786","ista":"Novarino G. 2017. The antisocial side of antibiotics. Science Translational Medicine. 9(387), 2786.","short":"G. Novarino, Science Translational Medicine 9 (2017).","mla":"Novarino, Gaia. “The Antisocial Side of Antibiotics.” Science Translational Medicine, vol. 9, no. 387, 2786, American Association for the Advancement of Science, 2017, doi:10.1126/scitranslmed.aan2786.","chicago":"Novarino, Gaia. “The Antisocial Side of Antibiotics.” Science Translational Medicine. American Association for the Advancement of Science, 2017. https://doi.org/10.1126/scitranslmed.aan2786."},"publication":"Science Translational Medicine","quality_controlled":"1"},{"abstract":[{"lang":"eng","text":"Rett syndrome modeling in monkey mirrors the human disorder."}],"issue":"393","publist_id":"7019","article_number":"eaan8196","type":"journal_article","author":[{"full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino"}],"date_updated":"2021-01-12T08:09:29Z","date_created":"2018-12-11T11:47:56Z","volume":9,"oa_version":"None","user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","_id":"689","year":"2017","status":"public","publication_status":"published","title":"Rett syndrome modeling goes simian","publisher":"American Association for the Advancement of Science","intvolume":" 9","department":[{"_id":"GaNo"}],"day":"07","month":"06","publication_identifier":{"issn":["19466234"]},"scopus_import":1,"date_published":"2017-06-07T00:00:00Z","doi":"10.1126/scitranslmed.aan8196","language":[{"iso":"eng"}],"publication":"Science Translational Medicine","citation":{"chicago":"Novarino, Gaia. “Rett Syndrome Modeling Goes Simian.” Science Translational Medicine. American Association for the Advancement of Science, 2017. https://doi.org/10.1126/scitranslmed.aan8196.","mla":"Novarino, Gaia. “Rett Syndrome Modeling Goes Simian.” Science Translational Medicine, vol. 9, no. 393, eaan8196, American Association for the Advancement of Science, 2017, doi:10.1126/scitranslmed.aan8196.","short":"G. Novarino, Science Translational Medicine 9 (2017).","ista":"Novarino G. 2017. Rett syndrome modeling goes simian. Science Translational Medicine. 9(393), eaan8196.","ieee":"G. Novarino, “Rett syndrome modeling goes simian,” Science Translational Medicine, vol. 9, no. 393. American Association for the Advancement of Science, 2017.","apa":"Novarino, G. (2017). Rett syndrome modeling goes simian. Science Translational Medicine. American Association for the Advancement of Science. https://doi.org/10.1126/scitranslmed.aan8196","ama":"Novarino G. Rett syndrome modeling goes simian. Science Translational Medicine. 2017;9(393). doi:10.1126/scitranslmed.aan8196"},"quality_controlled":"1"},{"type":"journal_article","issue":"399","publist_id":"6993","abstract":[{"text":"Leading autism-associated mutation in mouse partially mimics human disorder.\r\n\r\n","lang":"eng"}],"_id":"702","year":"2017","user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","publisher":"American Association for the Advancement of Science","department":[{"_id":"GaNo"}],"intvolume":" 9","publication_status":"published","title":"The riddle of CHD8 haploinsufficiency in autism spectrum disorder","status":"public","author":[{"last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia"}],"volume":9,"oa_version":"None","date_created":"2018-12-11T11:48:01Z","date_updated":"2021-01-12T08:11:31Z","scopus_import":1,"publication_identifier":{"issn":["19466234"]},"day":"19","month":"07","citation":{"chicago":"Novarino, Gaia. “The Riddle of CHD8 Haploinsufficiency in Autism Spectrum Disorder.” Science Translational Medicine. American Association for the Advancement of Science, 2017. https://doi.org/10.1126/scitranslmed.aao0972.","short":"G. Novarino, Science Translational Medicine 9 (2017) eaao0972.","mla":"Novarino, Gaia. “The Riddle of CHD8 Haploinsufficiency in Autism Spectrum Disorder.” Science Translational Medicine, vol. 9, no. 399, American Association for the Advancement of Science, 2017, p. eaao0972, doi:10.1126/scitranslmed.aao0972.","ieee":"G. Novarino, “The riddle of CHD8 haploinsufficiency in autism spectrum disorder,” Science Translational Medicine, vol. 9, no. 399. American Association for the Advancement of Science, p. eaao0972, 2017.","apa":"Novarino, G. (2017). The riddle of CHD8 haploinsufficiency in autism spectrum disorder. Science Translational Medicine. American Association for the Advancement of Science. https://doi.org/10.1126/scitranslmed.aao0972","ista":"Novarino G. 2017. The riddle of CHD8 haploinsufficiency in autism spectrum disorder. Science Translational Medicine. 9(399), eaao0972.","ama":"Novarino G. The riddle of CHD8 haploinsufficiency in autism spectrum disorder. Science Translational Medicine. 2017;9(399):eaao0972. doi:10.1126/scitranslmed.aao0972"},"publication":"Science Translational Medicine","page":"eaao0972","quality_controlled":"1","doi":"10.1126/scitranslmed.aao0972","date_published":"2017-07-19T00:00:00Z","language":[{"iso":"eng"}]},{"publisher":"American Association for the Advancement of Science","intvolume":" 9","department":[{"_id":"GaNo"}],"status":"public","title":"More excitation for Rett syndrome","publication_status":"published","_id":"715","year":"2017","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","oa_version":"None","volume":9,"date_created":"2018-12-11T11:48:06Z","date_updated":"2021-01-12T08:12:04Z","author":[{"first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"}],"type":"journal_article","article_number":"aao4218","issue":"405","publist_id":"6968","abstract":[{"lang":"eng","text":"D-cycloserine ameliorates breathing abnormalities and survival rate in a mouse model of Rett syndrome."}],"quality_controlled":"1","citation":{"ieee":"G. Novarino, “More excitation for Rett syndrome,” Science Translational Medicine, vol. 9, no. 405. American Association for the Advancement of Science, 2017.","apa":"Novarino, G. (2017). More excitation for Rett syndrome. Science Translational Medicine. American Association for the Advancement of Science. https://doi.org/10.1126/scitranslmed.aao4218","ista":"Novarino G. 2017. More excitation for Rett syndrome. Science Translational Medicine. 9(405), aao4218.","ama":"Novarino G. More excitation for Rett syndrome. Science Translational Medicine. 2017;9(405). doi:10.1126/scitranslmed.aao4218","chicago":"Novarino, Gaia. “More Excitation for Rett Syndrome.” Science Translational Medicine. American Association for the Advancement of Science, 2017. https://doi.org/10.1126/scitranslmed.aao4218.","short":"G. Novarino, Science Translational Medicine 9 (2017).","mla":"Novarino, Gaia. “More Excitation for Rett Syndrome.” Science Translational Medicine, vol. 9, no. 405, aao4218, American Association for the Advancement of Science, 2017, doi:10.1126/scitranslmed.aao4218."},"publication":"Science Translational Medicine","language":[{"iso":"eng"}],"doi":"10.1126/scitranslmed.aao4218","date_published":"2017-08-30T00:00:00Z","scopus_import":1,"publication_identifier":{"issn":["19466234"]},"day":"30","month":"08"},{"status":"public","publication_status":"published","title":"The science of love in ASD and ADHD","department":[{"_id":"GaNo"}],"intvolume":" 9","publisher":"American Association for the Advancement of Science","_id":"731","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","year":"2017","date_created":"2018-12-11T11:48:12Z","date_updated":"2021-01-12T08:12:57Z","oa_version":"None","volume":9,"author":[{"full_name":"Novarino, Gaia","last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"}],"article_number":"eaap8168","type":"journal_article","abstract":[{"lang":"eng","text":"Genetic variations in the oxytocin receptor gene affect patients with ASD and ADHD differently."}],"publist_id":"6938","issue":"411","quality_controlled":"1","publication":"Science Translational Medicine","citation":{"ieee":"G. Novarino, “The science of love in ASD and ADHD,” Science Translational Medicine, vol. 9, no. 411. American Association for the Advancement of Science, 2017.","apa":"Novarino, G. (2017). The science of love in ASD and ADHD. Science Translational Medicine. American Association for the Advancement of Science. https://doi.org/10.1126/scitranslmed.aap8168","ista":"Novarino G. 2017. The science of love in ASD and ADHD. Science Translational Medicine. 9(411), eaap8168.","ama":"Novarino G. The science of love in ASD and ADHD. Science Translational Medicine. 2017;9(411). doi:10.1126/scitranslmed.aap8168","chicago":"Novarino, Gaia. “The Science of Love in ASD and ADHD.” Science Translational Medicine. American Association for the Advancement of Science, 2017. https://doi.org/10.1126/scitranslmed.aap8168.","short":"G. Novarino, Science Translational Medicine 9 (2017).","mla":"Novarino, Gaia. “The Science of Love in ASD and ADHD.” Science Translational Medicine, vol. 9, no. 411, eaap8168, American Association for the Advancement of Science, 2017, doi:10.1126/scitranslmed.aap8168."},"language":[{"iso":"eng"}],"doi":"10.1126/scitranslmed.aap8168","date_published":"2017-10-11T00:00:00Z","scopus_import":1,"day":"11","month":"10","publication_identifier":{"issn":["19466234"]}},{"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"pmid":["27690184"],"isi":["000392487100005"]},"oa":1,"isi":1,"quality_controlled":"1","doi":"10.1111/ejn.13418","language":[{"iso":"eng"}],"month":"01","acknowledgement":"This work was supported by grants of the Austrian Science Fund (FWF) P23585B09 to M.W. and F3506 to H.H.S. and the “Wiener Wissenschafts-, Forschungs- und Technologiefonds” (Vienna Science and Technology Fund; WWTF) CS15-033 to M.W.","year":"2017","pmid":1,"publication_status":"published","department":[{"_id":"GaNo"}],"publisher":"Wiley-Blackwell","author":[{"first_name":"Ulrich","last_name":"Sauerzopf","full_name":"Sauerzopf, Ulrich"},{"id":"42C9F57E-F248-11E8-B48F-1D18A9856A87","first_name":"Roberto","last_name":"Sacco","full_name":"Sacco, Roberto"},{"orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia","full_name":"Novarino, Gaia"},{"full_name":"Niello, Marco","last_name":"Niello","first_name":"Marco"},{"full_name":"Weidenauer, Ana","last_name":"Weidenauer","first_name":"Ana"},{"last_name":"Praschak Rieder","first_name":"Nicole","full_name":"Praschak Rieder, Nicole"},{"last_name":"Sitte","first_name":"Harald","full_name":"Sitte, Harald"},{"last_name":"Willeit","first_name":"Matthaeus","full_name":"Willeit, Matthaeus"}],"date_created":"2018-12-11T11:50:50Z","date_updated":"2023-09-20T11:16:01Z","volume":45,"file_date_updated":"2020-07-14T12:44:39Z","publist_id":"6106","publication":"European Journal of Neuroscience","citation":{"mla":"Sauerzopf, Ulrich, et al. “Are Reprogrammed Cells a Useful Tool for Studying Dopamine Dysfunction in Psychotic Disorders? A Review of the Current Evidence.” European Journal of Neuroscience, vol. 45, no. 1, Wiley-Blackwell, 2017, pp. 45–57, doi:10.1111/ejn.13418.","short":"U. Sauerzopf, R. Sacco, G. Novarino, M. Niello, A. Weidenauer, N. Praschak Rieder, H. Sitte, M. Willeit, European Journal of Neuroscience 45 (2017) 45–57.","chicago":"Sauerzopf, Ulrich, Roberto Sacco, Gaia Novarino, Marco Niello, Ana Weidenauer, Nicole Praschak Rieder, Harald Sitte, and Matthaeus Willeit. “Are Reprogrammed Cells a Useful Tool for Studying Dopamine Dysfunction in Psychotic Disorders? A Review of the Current Evidence.” European Journal of Neuroscience. Wiley-Blackwell, 2017. https://doi.org/10.1111/ejn.13418.","ama":"Sauerzopf U, Sacco R, Novarino G, et al. Are reprogrammed cells a useful tool for studying dopamine dysfunction in psychotic disorders? A review of the current evidence. European Journal of Neuroscience. 2017;45(1):45-57. doi:10.1111/ejn.13418","ista":"Sauerzopf U, Sacco R, Novarino G, Niello M, Weidenauer A, Praschak Rieder N, Sitte H, Willeit M. 2017. Are reprogrammed cells a useful tool for studying dopamine dysfunction in psychotic disorders? A review of the current evidence. European Journal of Neuroscience. 45(1), 45–57.","ieee":"U. Sauerzopf et al., “Are reprogrammed cells a useful tool for studying dopamine dysfunction in psychotic disorders? A review of the current evidence,” European Journal of Neuroscience, vol. 45, no. 1. Wiley-Blackwell, pp. 45–57, 2017.","apa":"Sauerzopf, U., Sacco, R., Novarino, G., Niello, M., Weidenauer, A., Praschak Rieder, N., … Willeit, M. (2017). Are reprogrammed cells a useful tool for studying dopamine dysfunction in psychotic disorders? A review of the current evidence. European Journal of Neuroscience. Wiley-Blackwell. https://doi.org/10.1111/ejn.13418"},"article_type":"review","page":"45 - 57","date_published":"2017-01-01T00:00:00Z","scopus_import":"1","day":"01","article_processing_charge":"No","has_accepted_license":"1","_id":"1228","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","title":"Are reprogrammed cells a useful tool for studying dopamine dysfunction in psychotic disorders? A review of the current evidence","ddc":["616"],"status":"public","intvolume":" 45","pubrep_id":"738","file":[{"checksum":"c572cf02be8fbb7020cfcfb892182e4c","date_updated":"2020-07-14T12:44:39Z","date_created":"2018-12-12T10:10:48Z","file_id":"4838","relation":"main_file","creator":"system","file_size":169145,"content_type":"application/pdf","access_level":"open_access","file_name":"IST-2017-738-v1+1_Sauerzopf_et_al-2017-European_Journal_of_Neuroscience.pdf"}],"oa_version":"Published Version","type":"journal_article","abstract":[{"lang":"eng","text":"Since 2006, reprogrammed cells have increasingly been used as a biomedical research technique in addition to neuro-psychiatric methods. These rapidly evolving techniques allow for the generation of neuronal sub-populations, and have sparked interest not only in monogenetic neuro-psychiatric diseases, but also in poly-genetic and poly-aetiological disorders such as schizophrenia (SCZ) and bipolar disorder (BPD). This review provides a summary of 19 publications on reprogrammed adult somatic cells derived from patients with SCZ, and five publications using this technique in patients with BPD. As both disorders are complex and heterogeneous, there is a plurality of hypotheses to be tested in vitro. In SCZ, data on alterations of dopaminergic transmission in vitro are sparse, despite the great explanatory power of the so-called DA hypothesis of SCZ. Some findings correspond to perturbations of cell energy metabolism, and observations in reprogrammed cells suggest neuro-developmental alterations. Some studies also report on the efficacy of medicinal compounds to revert alterations observed in cellular models. However, due to the paucity of replication studies, no comprehensive conclusions can be drawn from studies using reprogrammed cells at the present time. In the future, findings from cell culture methods need to be integrated with clinical, epidemiological, pharmacological and imaging data in order to generate a more comprehensive picture of SCZ and BPD."}],"issue":"1"},{"month":"12","language":[{"iso":"eng"}],"doi":"10.1016/j.cell.2016.11.013","quality_controlled":"1","project":[{"grant_number":"F03523","_id":"25473368-B435-11E9-9278-68D0E5697425","name":"Transmembrane Transporters in Health and Disease","call_identifier":"FWF"}],"oa":1,"file_date_updated":"2020-07-14T12:44:37Z","publist_id":"6170","date_created":"2018-12-11T11:50:35Z","date_updated":"2024-03-28T23:30:12Z","volume":167,"author":[{"id":"2ABCE612-F248-11E8-B48F-1D18A9856A87","first_name":"Dora-Clara","last_name":"Tarlungeanu","full_name":"Tarlungeanu, Dora-Clara"},{"full_name":"Deliu, Elena","first_name":"Elena","last_name":"Deliu","id":"37A40D7E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7370-5293"},{"last_name":"Dotter","first_name":"Christoph","orcid":"0000-0002-9033-9096","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","full_name":"Dotter, Christoph"},{"first_name":"Majdi","last_name":"Kara","full_name":"Kara, Majdi"},{"full_name":"Janiesch, Philipp","last_name":"Janiesch","first_name":"Philipp"},{"full_name":"Scalise, Mariafrancesca","last_name":"Scalise","first_name":"Mariafrancesca"},{"full_name":"Galluccio, Michele","first_name":"Michele","last_name":"Galluccio"},{"full_name":"Tesulov, Mateja","first_name":"Mateja","last_name":"Tesulov"},{"full_name":"Morelli, Emanuela","last_name":"Morelli","first_name":"Emanuela","id":"3F4D1282-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Sönmez, Fatma","first_name":"Fatma","last_name":"Sönmez"},{"last_name":"Bilgüvar","first_name":"Kaya","full_name":"Bilgüvar, Kaya"},{"first_name":"Ryuichi","last_name":"Ohgaki","full_name":"Ohgaki, Ryuichi"},{"full_name":"Kanai, Yoshikatsu","last_name":"Kanai","first_name":"Yoshikatsu"},{"full_name":"Johansen, Anide","first_name":"Anide","last_name":"Johansen"},{"full_name":"Esharif, Seham","last_name":"Esharif","first_name":"Seham"},{"first_name":"Tawfeg","last_name":"Ben Omran","full_name":"Ben Omran, Tawfeg"},{"full_name":"Topcu, Meral","first_name":"Meral","last_name":"Topcu"},{"last_name":"Schlessinger","first_name":"Avner","full_name":"Schlessinger, Avner"},{"full_name":"Indiveri, Cesare","first_name":"Cesare","last_name":"Indiveri"},{"first_name":"Kent","last_name":"Duncan","full_name":"Duncan, Kent"},{"last_name":"Caglayan","first_name":"Ahmet","full_name":"Caglayan, Ahmet"},{"last_name":"Günel","first_name":"Murat","full_name":"Günel, Murat"},{"full_name":"Gleeson, Joseph","first_name":"Joseph","last_name":"Gleeson"},{"full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino"}],"related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"395"}]},"publication_status":"published","publisher":"Cell Press","department":[{"_id":"GaNo"}],"year":"2016","acknowledgement":"This work was supported by NICHD (P01HD070494) and SFARI (grant 275275) to J.G.G., and FWF (SFB35_3523) to G.N.\r\nWe thank A.C. Manzano, Mike Liu, and F. Marr for technical assistance, and R. Shigemoto and the IST Austria Electron Microscopy (EM) Facility for assistance. We acknowledge support from CIDR for genome-wide SNP analysis (X01HG008823) and Broad Institute Center for Mendelian Disorders (UM1HG008900 to D. MacArthur), the Yale Center for Mendelian Disorders (U54HG006504 to M.G.), the Gregory M. Kiez and Mehmet Kutman Foundation (M.G.), Italian Ministry of Instruction University and Research (PON01_00937 to C.I.), and NIH (R01-GM108911 to A.S.). This work was supported by NICHD (P01HD070494) and SFARI (grant 275275) to J.G.G., and FWF (SFB35_3523) to G.N.\r\n\r\n#EMFacility","day":"01","article_processing_charge":"No","has_accepted_license":"1","scopus_import":"1","date_published":"2016-12-01T00:00:00Z","article_type":"original","page":"1481 - 1494","publication":"Cell","citation":{"mla":"Tarlungeanu, Dora-Clara, et al. “Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder.” Cell, vol. 167, no. 6, Cell Press, 2016, pp. 1481–94, doi:10.1016/j.cell.2016.11.013.","short":"D.-C. Tarlungeanu, E. Deliu, C. Dotter, M. Kara, P. Janiesch, M. Scalise, M. Galluccio, M. Tesulov, E. Morelli, F. Sönmez, K. Bilgüvar, R. Ohgaki, Y. Kanai, A. Johansen, S. Esharif, T. Ben Omran, M. Topcu, A. Schlessinger, C. Indiveri, K. Duncan, A. Caglayan, M. Günel, J. Gleeson, G. Novarino, Cell 167 (2016) 1481–1494.","chicago":"Tarlungeanu, Dora-Clara, Elena Deliu, Christoph Dotter, Majdi Kara, Philipp Janiesch, Mariafrancesca Scalise, Michele Galluccio, et al. “Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder.” Cell. Cell Press, 2016. https://doi.org/10.1016/j.cell.2016.11.013.","ama":"Tarlungeanu D-C, Deliu E, Dotter C, et al. Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder. Cell. 2016;167(6):1481-1494. doi:10.1016/j.cell.2016.11.013","ista":"Tarlungeanu D-C, Deliu E, Dotter C, Kara M, Janiesch P, Scalise M, Galluccio M, Tesulov M, Morelli E, Sönmez F, Bilgüvar K, Ohgaki R, Kanai Y, Johansen A, Esharif S, Ben Omran T, Topcu M, Schlessinger A, Indiveri C, Duncan K, Caglayan A, Günel M, Gleeson J, Novarino G. 2016. Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder. Cell. 167(6), 1481–1494.","ieee":"D.-C. Tarlungeanu et al., “Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder,” Cell, vol. 167, no. 6. Cell Press, pp. 1481–1494, 2016.","apa":"Tarlungeanu, D.-C., Deliu, E., Dotter, C., Kara, M., Janiesch, P., Scalise, M., … Novarino, G. (2016). Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder. Cell. Cell Press. https://doi.org/10.1016/j.cell.2016.11.013"},"abstract":[{"text":"Autism spectrum disorders (ASD) are a group of genetic disorders often overlapping with other neurological conditions. We previously described abnormalities in the branched-chain amino acid (BCAA) catabolic pathway as a cause of ASD. Here, we show that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid transporter localized at the blood brain barrier (BBB), has an essential role in maintaining normal levels of brain BCAAs. In mice, deletion of Slc7a5 from the endothelial cells of the BBB leads to atypical brain amino acid profile, abnormal mRNA translation, and severe neurological abnormalities. Furthermore, we identified several patients with autistic traits and motor delay carrying deleterious homozygous mutations in the SLC7A5 gene. Finally, we demonstrate that BCAA intracerebroventricular administration ameliorates abnormal behaviors in adult mutant mice. Our data elucidate a neurological syndrome defined by SLC7A5 mutations and support an essential role for the BCAA in human brain function.","lang":"eng"}],"issue":"6","type":"journal_article","file":[{"file_id":"5030","relation":"main_file","date_updated":"2020-07-14T12:44:37Z","date_created":"2018-12-12T10:13:44Z","checksum":"7fe01ab12a6610d3db421e0136db2f77","file_name":"IST-2017-771-v1+1_Tarlungeanu_et_al._Final_edited.pdf","access_level":"open_access","creator":"system","file_size":73907957,"content_type":"application/pdf"}],"oa_version":"Submitted Version","pubrep_id":"771","title":"Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder","status":"public","ddc":["576","616"],"intvolume":" 167","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","_id":"1183"},{"publication":"European Journal of Human Genetics","citation":{"ama":"Kuechler A, Zink A, Wieland T, et al. Loss-of-function variants of SETD5 cause intellectual disability and the core phenotype of microdeletion 3p25.3 syndrome. European Journal of Human Genetics. 2015;23(6):753-760. doi:10.1038/ejhg.2014.165","ista":"Kuechler A, Zink A, Wieland T, Lüdecke H, Cremer K, Salviati L, Magini P, Najafi K, Zweier C, Czeschik J, Aretz S, Endele S, Tamburrino F, Pinato C, Clementi M, Gundlach J, Maylahn C, Mazzanti L, Wohlleber E, Schwarzmayr T, Kariminejad R, Schlessinger A, Wieczorek D, Strom T, Novarino G, Engels H. 2015. Loss-of-function variants of SETD5 cause intellectual disability and the core phenotype of microdeletion 3p25.3 syndrome. European Journal of Human Genetics. 23(6), 753–760.","apa":"Kuechler, A., Zink, A., Wieland, T., Lüdecke, H., Cremer, K., Salviati, L., … Engels, H. (2015). Loss-of-function variants of SETD5 cause intellectual disability and the core phenotype of microdeletion 3p25.3 syndrome. European Journal of Human Genetics. Nature Publishing Group. https://doi.org/10.1038/ejhg.2014.165","ieee":"A. Kuechler et al., “Loss-of-function variants of SETD5 cause intellectual disability and the core phenotype of microdeletion 3p25.3 syndrome,” European Journal of Human Genetics, vol. 23, no. 6. Nature Publishing Group, pp. 753–760, 2015.","mla":"Kuechler, Alma, et al. “Loss-of-Function Variants of SETD5 Cause Intellectual Disability and the Core Phenotype of Microdeletion 3p25.3 Syndrome.” European Journal of Human Genetics, vol. 23, no. 6, Nature Publishing Group, 2015, pp. 753–60, doi:10.1038/ejhg.2014.165.","short":"A. Kuechler, A. Zink, T. Wieland, H. Lüdecke, K. Cremer, L. Salviati, P. Magini, K. Najafi, C. Zweier, J. Czeschik, S. Aretz, S. Endele, F. Tamburrino, C. Pinato, M. Clementi, J. Gundlach, C. Maylahn, L. Mazzanti, E. Wohlleber, T. Schwarzmayr, R. Kariminejad, A. Schlessinger, D. Wieczorek, T. Strom, G. Novarino, H. Engels, European Journal of Human Genetics 23 (2015) 753–760.","chicago":"Kuechler, Alma, Alexander Zink, Thomas Wieland, Hermann Lüdecke, Kirsten Cremer, Leonardo Salviati, Pamela Magini, et al. “Loss-of-Function Variants of SETD5 Cause Intellectual Disability and the Core Phenotype of Microdeletion 3p25.3 Syndrome.” European Journal of Human Genetics. Nature Publishing Group, 2015. https://doi.org/10.1038/ejhg.2014.165."},"page":"753 - 760","date_published":"2015-06-15T00:00:00Z","day":"15","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"1789","status":"public","title":"Loss-of-function variants of SETD5 cause intellectual disability and the core phenotype of microdeletion 3p25.3 syndrome","intvolume":" 23","oa_version":"Submitted Version","type":"journal_article","abstract":[{"lang":"eng","text":"Intellectual disability (ID) has an estimated prevalence of 2-3%. Due to its extreme heterogeneity, the genetic basis of ID remains elusive in many cases. Recently, whole exome sequencing (WES) studies revealed that a large proportion of sporadic cases are caused by de novo gene variants. To identify further genes involved in ID, we performed WES in 250 patients with unexplained ID and their unaffected parents and included exomes of 51 previously sequenced child-parents trios in the analysis. Exome analysis revealed de novo intragenic variants in SET domain-containing 5 (SETD5) in two patients. One patient carried a nonsense variant, and the other an 81 bp deletion located across a splice-donor site. Chromosomal microarray diagnostics further identified four de novo non-recurrent microdeletions encompassing SETD5. CRISPR/Cas9 mutation modelling of the two intragenic variants demonstrated nonsense-mediated decay of the resulting transcripts, pointing to a loss-of-function (LoF) and haploinsufficiency as the common disease-causing mechanism of intragenic SETD5 sequence variants and SETD5-containing microdeletions. In silico domain prediction of SETD5, a predicted SET domain-containing histone methyltransferase (HMT), substantiated the presence of a SET domain and identified a novel putative PHD domain, strengthening a functional link to well-known histone-modifying ID genes. All six patients presented with ID and certain facial dysmorphisms, suggesting that SETD5 sequence variants contribute substantially to the microdeletion 3p25.3 phenotype. The present report of two SETD5 LoF variants in 301 patients demonstrates a prevalence of 0.7% and thus SETD5 variants as a relatively frequent cause of ID."}],"issue":"6","external_id":{"pmid":["25138099"]},"oa":1,"main_file_link":[{"url":"http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4795044/","open_access":"1"}],"quality_controlled":"1","doi":"10.1038/ejhg.2014.165","language":[{"iso":"eng"}],"month":"06","year":"2015","pmid":1,"publication_status":"published","publisher":"Nature Publishing Group","department":[{"_id":"GaNo"}],"author":[{"last_name":"Kuechler","first_name":"Alma","full_name":"Kuechler, Alma"},{"first_name":"Alexander","last_name":"Zink","full_name":"Zink, Alexander"},{"full_name":"Wieland, Thomas","first_name":"Thomas","last_name":"Wieland"},{"full_name":"Lüdecke, Hermann","first_name":"Hermann","last_name":"Lüdecke"},{"full_name":"Cremer, Kirsten","first_name":"Kirsten","last_name":"Cremer"},{"full_name":"Salviati, Leonardo","first_name":"Leonardo","last_name":"Salviati"},{"first_name":"Pamela","last_name":"Magini","full_name":"Magini, Pamela"},{"full_name":"Najafi, Kimia","last_name":"Najafi","first_name":"Kimia"},{"last_name":"Zweier","first_name":"Christiane","full_name":"Zweier, Christiane"},{"first_name":"Johanna","last_name":"Czeschik","full_name":"Czeschik, Johanna"},{"last_name":"Aretz","first_name":"Stefan","full_name":"Aretz, Stefan"},{"full_name":"Endele, Sabine","last_name":"Endele","first_name":"Sabine"},{"full_name":"Tamburrino, Federica","first_name":"Federica","last_name":"Tamburrino"},{"full_name":"Pinato, Claudia","first_name":"Claudia","last_name":"Pinato"},{"last_name":"Clementi","first_name":"Maurizio","full_name":"Clementi, Maurizio"},{"last_name":"Gundlach","first_name":"Jasmin","full_name":"Gundlach, Jasmin"},{"full_name":"Maylahn, Carina","last_name":"Maylahn","first_name":"Carina"},{"last_name":"Mazzanti","first_name":"Laura","full_name":"Mazzanti, Laura"},{"last_name":"Wohlleber","first_name":"Eva","full_name":"Wohlleber, Eva"},{"last_name":"Schwarzmayr","first_name":"Thomas","full_name":"Schwarzmayr, Thomas"},{"full_name":"Kariminejad, Roxana","last_name":"Kariminejad","first_name":"Roxana"},{"full_name":"Schlessinger, Avner","last_name":"Schlessinger","first_name":"Avner"},{"first_name":"Dagmar","last_name":"Wieczorek","full_name":"Wieczorek, Dagmar"},{"full_name":"Strom, Tim","last_name":"Strom","first_name":"Tim"},{"full_name":"Novarino, Gaia","last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Engels","first_name":"Hartmut","full_name":"Engels, Hartmut"}],"date_updated":"2021-01-12T06:53:12Z","date_created":"2018-12-11T11:54:01Z","volume":23,"publist_id":"5324"},{"day":"18","month":"06","date_published":"2014-06-18T00:00:00Z","doi":"10.1016/j.neuron.2014.04.036","citation":{"chicago":"Baek, Seungtae, Géraldine Kerjan, Stephanie Bielas, Jieun Lee, Ali Fenstermaker, Gaia Novarino, and Joseph Gleeson. “Off-Target Effect of Doublecortin Family ShRNA on Neuronal Migration Associated with Endogenous MicroRNA Dysregulation.” Neuron. Elsevier, 2014. https://doi.org/10.1016/j.neuron.2014.04.036.","mla":"Baek, Seungtae, et al. “Off-Target Effect of Doublecortin Family ShRNA on Neuronal Migration Associated with Endogenous MicroRNA Dysregulation.” Neuron, vol. 82, no. 6, Elsevier, 2014, pp. 1255–62, doi:10.1016/j.neuron.2014.04.036.","short":"S. Baek, G. Kerjan, S. Bielas, J. Lee, A. Fenstermaker, G. Novarino, J. Gleeson, Neuron 82 (2014) 1255–1262.","ista":"Baek S, Kerjan G, Bielas S, Lee J, Fenstermaker A, Novarino G, Gleeson J. 2014. Off-target effect of doublecortin family shRNA on neuronal migration associated with endogenous MicroRNA dysregulation. Neuron. 82(6), 1255–1262.","apa":"Baek, S., Kerjan, G., Bielas, S., Lee, J., Fenstermaker, A., Novarino, G., & Gleeson, J. (2014). Off-target effect of doublecortin family shRNA on neuronal migration associated with endogenous MicroRNA dysregulation. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2014.04.036","ieee":"S. Baek et al., “Off-target effect of doublecortin family shRNA on neuronal migration associated with endogenous MicroRNA dysregulation,” Neuron, vol. 82, no. 6. Elsevier, pp. 1255–1262, 2014.","ama":"Baek S, Kerjan G, Bielas S, et al. Off-target effect of doublecortin family shRNA on neuronal migration associated with endogenous MicroRNA dysregulation. Neuron. 2014;82(6):1255-1262. doi:10.1016/j.neuron.2014.04.036"},"publication":"Neuron","page":"1255 - 1262","quality_controlled":0,"issue":"6","publist_id":"5322","abstract":[{"lang":"eng","text":"Acute gene inactivation using short hairpin RNA (shRNA, knockdown) in developing brain is a powerful technique to study genetic function; however, discrepancies between knockdown and knockout murine phenotypes have left unanswered questions. For example, doublecortin (Dcx) knockdown but not knockout shows a neocortical neuronal migration phenotype. Here we report that in utero electroporation of shRNA, but not siRNA or miRNA, to Dcx demonstrates a migration phenotype in Dcx knockouts akin to the effect in wild-type mice, suggestingshRNA-mediated off-target toxicity. This effect wasnot limited to Dcx, as it was observed in Dclk1 knockouts, as well as with a fraction of scrambled shRNAs, suggesting a sequence-dependent but not sequence-specific effect. Profiling RNAs from electroporated cells showed a defect in endogenous let7 miRNA levels, and disruption of let7 or Dicer recapitulated the migration defect. The results suggest that shRNA-mediated knockdown can produce untoward migration effects by altering endogenous miRNA pathways."}],"extern":1,"type":"journal_article","author":[{"full_name":"Baek, SeungTae","first_name":"Seungtae","last_name":"Baek"},{"full_name":"Kerjan, Géraldine","first_name":"Géraldine","last_name":"Kerjan"},{"full_name":"Bielas, Stephanie L","last_name":"Bielas","first_name":"Stephanie"},{"full_name":"Lee, Jieun","first_name":"Jieun","last_name":"Lee"},{"full_name":"Fenstermaker, Ali G","last_name":"Fenstermaker","first_name":"Ali"},{"first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","full_name":"Gaia Novarino"},{"full_name":"Gleeson, Joseph G","last_name":"Gleeson","first_name":"Joseph"}],"volume":82,"date_created":"2018-12-11T11:54:01Z","date_updated":"2021-01-12T06:53:13Z","_id":"1791","acknowledgement":"This work was supported by the National Institutes of Health R01NS41537. G.K. was supported by an EMBO Long Term Fellowship, S.L.B. by the A.P. Giannini Fellowship, and A.G.F. by the Brain Behavior Research Foundation","year":"2014","publisher":"Elsevier","intvolume":" 82","publication_status":"published","status":"public","title":"Off-target effect of doublecortin family shRNA on neuronal migration associated with endogenous MicroRNA dysregulation"},{"intvolume":" 343","status":"public","title":"Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"1916","oa_version":"Submitted Version","type":"journal_article","issue":"6170","abstract":[{"lang":"eng","text":"Hereditary spastic paraplegias (HSPs) are neurodegenerative motor neuron diseases characterized by progressive age-dependent loss of corticospinal motor tract function. Although the genetic basis is partly understood, only a fraction of cases can receive a genetic diagnosis, and a global view of HSP is lacking. By using whole-exome sequencing in combination with network analysis, we identified 18 previously unknown putative HSP genes and validated nearly all of these genes functionally or genetically. The pathways highlighted by these mutations link HSP to cellular transport, nucleotide metabolism, and synapse and axon development. Network analysis revealed a host of further candidate genes, of which three were mutated in our cohort. Our analysis links HSP to other neurodegenerative disorders and can facilitate gene discovery and mechanistic understanding of disease."}],"page":"506 - 511","article_type":"original","citation":{"mla":"Novarino, Gaia, et al. “Exome Sequencing Links Corticospinal Motor Neuron Disease to Common Neurodegenerative Disorders.” Science, vol. 343, no. 6170, American Association for the Advancement of Science, 2014, pp. 506–11, doi:10.1126/science.1247363.","short":"G. Novarino, A. Fenstermaker, M. Zaki, M. Hofree, J. Silhavy, A. Heiberg, M. Abdellateef, B. Rosti, E. Scott, L. Mansour, A. Masri, H. Kayserili, J. Al Aama, G. Abdel Salam, A. Karminejad, M. Kara, B. Kara, B. Bozorgmehri, T. Ben Omran, F. Mojahedi, I. Mahmoud, N. Bouslam, A. Bouhouche, A. Benomar, S. Hanein, L. Raymond, S. Forlani, M. Mascaro, L. Selim, N. Shehata, N. Al Allawi, P. Bindu, M. Azam, M. Günel, A. Caglayan, K. Bilgüvar, A. Tolun, M. Issa, J. Schroth, E. Spencer, R. Rosti, N. Akizu, K. Vaux, A. Johansen, A. Koh, H. Megahed, A. Dürr, A. Brice, G. Stévanin, S. Gabriel, T. Ideker, J. Gleeson, Science 343 (2014) 506–511.","chicago":"Novarino, Gaia, Ali Fenstermaker, Maha Zaki, Matan Hofree, Jennifer Silhavy, Andrew Heiberg, Mostafa Abdellateef, et al. “Exome Sequencing Links Corticospinal Motor Neuron Disease to Common Neurodegenerative Disorders.” Science. American Association for the Advancement of Science, 2014. https://doi.org/10.1126/science.1247363.","ama":"Novarino G, Fenstermaker A, Zaki M, et al. Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders. Science. 2014;343(6170):506-511. doi:10.1126/science.1247363","ista":"Novarino G, Fenstermaker A, Zaki M, Hofree M, Silhavy J, Heiberg A, Abdellateef M, Rosti B, Scott E, Mansour L, Masri A, Kayserili H, Al Aama J, Abdel Salam G, Karminejad A, Kara M, Kara B, Bozorgmehri B, Ben Omran T, Mojahedi F, Mahmoud I, Bouslam N, Bouhouche A, Benomar A, Hanein S, Raymond L, Forlani S, Mascaro M, Selim L, Shehata N, Al Allawi N, Bindu P, Azam M, Günel M, Caglayan A, Bilgüvar K, Tolun A, Issa M, Schroth J, Spencer E, Rosti R, Akizu N, Vaux K, Johansen A, Koh A, Megahed H, Dürr A, Brice A, Stévanin G, Gabriel S, Ideker T, Gleeson J. 2014. Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders. Science. 343(6170), 506–511.","ieee":"G. Novarino et al., “Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders,” Science, vol. 343, no. 6170. American Association for the Advancement of Science, pp. 506–511, 2014.","apa":"Novarino, G., Fenstermaker, A., Zaki, M., Hofree, M., Silhavy, J., Heiberg, A., … Gleeson, J. (2014). Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.1247363"},"publication":"Science","date_published":"2014-01-31T00:00:00Z","scopus_import":1,"article_processing_charge":"No","day":"31","department":[{"_id":"GaNo"}],"publisher":"American Association for the Advancement of Science","publication_status":"published","pmid":1,"acknowledgement":"Supported by the Deutsche Forschungsgemeinschaft (G.N.)","year":"2014","volume":343,"date_updated":"2021-01-12T06:54:03Z","date_created":"2018-12-11T11:54:42Z","author":[{"orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia","full_name":"Novarino, Gaia"},{"full_name":"Fenstermaker, Ali","first_name":"Ali","last_name":"Fenstermaker"},{"first_name":"Maha","last_name":"Zaki","full_name":"Zaki, Maha"},{"last_name":"Hofree","first_name":"Matan","full_name":"Hofree, Matan"},{"full_name":"Silhavy, Jennifer","last_name":"Silhavy","first_name":"Jennifer"},{"full_name":"Heiberg, Andrew","first_name":"Andrew","last_name":"Heiberg"},{"full_name":"Abdellateef, Mostafa","last_name":"Abdellateef","first_name":"Mostafa"},{"first_name":"Başak","last_name":"Rosti","full_name":"Rosti, Başak"},{"last_name":"Scott","first_name":"Eric","full_name":"Scott, Eric"},{"last_name":"Mansour","first_name":"Lobna","full_name":"Mansour, Lobna"},{"first_name":"Amira","last_name":"Masri","full_name":"Masri, Amira"},{"first_name":"Hülya","last_name":"Kayserili","full_name":"Kayserili, Hülya"},{"first_name":"Jumana","last_name":"Al Aama","full_name":"Al Aama, Jumana"},{"first_name":"Ghada","last_name":"Abdel Salam","full_name":"Abdel Salam, Ghada"},{"full_name":"Karminejad, Ariana","first_name":"Ariana","last_name":"Karminejad"},{"full_name":"Kara, Majdi","last_name":"Kara","first_name":"Majdi"},{"last_name":"Kara","first_name":"Bülent","full_name":"Kara, Bülent"},{"first_name":"Bita","last_name":"Bozorgmehri","full_name":"Bozorgmehri, Bita"},{"last_name":"Ben Omran","first_name":"Tawfeg","full_name":"Ben Omran, Tawfeg"},{"first_name":"Faezeh","last_name":"Mojahedi","full_name":"Mojahedi, Faezeh"},{"full_name":"Mahmoud, Iman","first_name":"Iman","last_name":"Mahmoud"},{"full_name":"Bouslam, Naïma","last_name":"Bouslam","first_name":"Naïma"},{"last_name":"Bouhouche","first_name":"Ahmed","full_name":"Bouhouche, Ahmed"},{"full_name":"Benomar, Ali","last_name":"Benomar","first_name":"Ali"},{"last_name":"Hanein","first_name":"Sylvain","full_name":"Hanein, Sylvain"},{"full_name":"Raymond, Laure","last_name":"Raymond","first_name":"Laure"},{"last_name":"Forlani","first_name":"Sylvie","full_name":"Forlani, Sylvie"},{"full_name":"Mascaro, Massimo","first_name":"Massimo","last_name":"Mascaro"},{"last_name":"Selim","first_name":"Laila","full_name":"Selim, Laila"},{"first_name":"Nabil","last_name":"Shehata","full_name":"Shehata, Nabil"},{"first_name":"Nasir","last_name":"Al Allawi","full_name":"Al Allawi, Nasir"},{"last_name":"Bindu","first_name":"Parayil","full_name":"Bindu, Parayil"},{"full_name":"Azam, Matloob","last_name":"Azam","first_name":"Matloob"},{"full_name":"Günel, Murat","last_name":"Günel","first_name":"Murat"},{"full_name":"Caglayan, Ahmet","last_name":"Caglayan","first_name":"Ahmet"},{"full_name":"Bilgüvar, Kaya","first_name":"Kaya","last_name":"Bilgüvar"},{"full_name":"Tolun, Aslihan","first_name":"Aslihan","last_name":"Tolun"},{"first_name":"Mahmoud","last_name":"Issa","full_name":"Issa, Mahmoud"},{"full_name":"Schroth, Jana","last_name":"Schroth","first_name":"Jana"},{"last_name":"Spencer","first_name":"Emily","full_name":"Spencer, Emily"},{"full_name":"Rosti, Rasim","last_name":"Rosti","first_name":"Rasim"},{"last_name":"Akizu","first_name":"Naiara","full_name":"Akizu, Naiara"},{"full_name":"Vaux, Keith","first_name":"Keith","last_name":"Vaux"},{"first_name":"Anide","last_name":"Johansen","full_name":"Johansen, Anide"},{"first_name":"Alice","last_name":"Koh","full_name":"Koh, Alice"},{"last_name":"Megahed","first_name":"Hisham","full_name":"Megahed, Hisham"},{"full_name":"Dürr, Alexandra","first_name":"Alexandra","last_name":"Dürr"},{"first_name":"Alexis","last_name":"Brice","full_name":"Brice, Alexis"},{"full_name":"Stévanin, Giovanni","first_name":"Giovanni","last_name":"Stévanin"},{"last_name":"Gabriel","first_name":"Stacy","full_name":"Gabriel, Stacy"},{"full_name":"Ideker, Trey","first_name":"Trey","last_name":"Ideker"},{"full_name":"Gleeson, Joseph","last_name":"Gleeson","first_name":"Joseph"}],"publist_id":"5178","quality_controlled":"1","external_id":{"pmid":["24482476"]},"main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157572/"}],"oa":1,"language":[{"iso":"eng"}],"doi":"10.1126/science.1247363","month":"01"},{"author":[{"orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia","full_name":"Gaia Novarino"},{"last_name":"Baek","first_name":"Seungtae","full_name":"Baek, SeungTae"},{"full_name":"Gleeson, Joseph G","last_name":"Gleeson","first_name":"Joseph"}],"volume":80,"date_created":"2018-12-11T11:54:01Z","date_updated":"2021-01-12T06:53:13Z","year":"2013","_id":"1790","publisher":"Elsevier","intvolume":" 80","publication_status":"published","status":"public","title":"The sacred disease: The puzzling genetics of epileptic disorders","issue":"1","publist_id":"5323","abstract":[{"lang":"eng","text":"In the September 12, 2013 issue of Nature, the Epi4K Consortium (. Allen etal., 2013) reported sequencing 264patient trios with epileptic encephalopathies. The Consortium focused on genes exceptionally intolerant to sequence variations and found substantial interconnections with autism and intellectual disability gene networks."}],"extern":1,"type":"journal_article","doi":"10.1016/j.neuron.2013.09.019","date_published":"2013-10-02T00:00:00Z","citation":{"chicago":"Novarino, Gaia, Seungtae Baek, and Joseph Gleeson. “The Sacred Disease: The Puzzling Genetics of Epileptic Disorders.” Neuron. Elsevier, 2013. https://doi.org/10.1016/j.neuron.2013.09.019.","short":"G. Novarino, S. Baek, J. Gleeson, Neuron 80 (2013) 9–11.","mla":"Novarino, Gaia, et al. “The Sacred Disease: The Puzzling Genetics of Epileptic Disorders.” Neuron, vol. 80, no. 1, Elsevier, 2013, pp. 9–11, doi:10.1016/j.neuron.2013.09.019.","apa":"Novarino, G., Baek, S., & Gleeson, J. (2013). The sacred disease: The puzzling genetics of epileptic disorders. Neuron. Elsevier. https://doi.org/10.1016/j.neuron.2013.09.019","ieee":"G. Novarino, S. Baek, and J. Gleeson, “The sacred disease: The puzzling genetics of epileptic disorders,” Neuron, vol. 80, no. 1. Elsevier, pp. 9–11, 2013.","ista":"Novarino G, Baek S, Gleeson J. 2013. The sacred disease: The puzzling genetics of epileptic disorders. Neuron. 80(1), 9–11.","ama":"Novarino G, Baek S, Gleeson J. The sacred disease: The puzzling genetics of epileptic disorders. Neuron. 2013;80(1):9-11. doi:10.1016/j.neuron.2013.09.019"},"publication":"Neuron","page":"9 - 11","quality_controlled":0,"day":"02","month":"10"},{"type":"journal_article","publist_id":"4614","issue":"138","abstract":[{"text":"The translation of "next-generation" sequencing directly to the clinic is still being assessed but has the potential for genetic diseases to reduce costs, advance accuracy, and point to unsuspected yet treatable conditions. To study its capability in the clinic, we performed whole-exome sequencing in 118 probands with a diagnosis of a pediatric-onset neurodevelopmental disease in which most known causes had been excluded. Twenty-two genes not previously identified as disease-causing were identified in this study (19% of cohort), further establishing exome sequencing as a useful tool for gene discovery. New genes identified included EXOC8 in Joubert syndrome and GFM2 in a patient with microcephaly, simplified gyral pattern, and insulin-dependent diabetes. Exome sequencing uncovered 10 probands (8% of cohort) with mutations in genes known to cause a disease different from the initial diagnosis. Upon further medical evaluation, these mutations were found to account for each proband's disease, leading to a change in diagnosis, some of which led to changes in patient management. Our data provide proof of principle that genomic strategies are useful in clarifying diagnosis in a proportion of patients with neurodevelopmental disorders.","lang":"eng"}],"extern":1,"year":"2012","_id":"2313","publisher":"American Association for the Advancement of Science","intvolume":" 4","status":"public","publication_status":"published","title":"Exome sequencing can improve diagnosis and alter patient management","author":[{"first_name":"Tracy","last_name":"Dixon Salazar","full_name":"Dixon-Salazar, Tracy J"},{"first_name":"Jennifer","last_name":"Silhavy","full_name":"Silhavy, Jennifer L"},{"full_name":"Udpa, Nitin","last_name":"Udpa","first_name":"Nitin"},{"full_name":"Schroth, Jana","last_name":"Schroth","first_name":"Jana"},{"last_name":"Bielas","first_name":"Stephanie","full_name":"Bielas, Stephanie L"},{"first_name":"Ashleigh","last_name":"Schaffer","full_name":"Schaffer, Ashleigh E"},{"first_name":"Jesus","last_name":"Olvera","full_name":"Olvera, Jesus"},{"full_name":"Bafna, Vineet K","last_name":"Bafna","first_name":"Vineet"},{"last_name":"Zaki","first_name":"Maha","full_name":"Zaki, Maha S"},{"last_name":"Abdel Salam","first_name":"Ghada","full_name":"Abdel-Salam, Ghada M"},{"full_name":"Mansour, Lobna A","last_name":"Mansour","first_name":"Lobna"},{"last_name":"Selim","first_name":"Laila","full_name":"Selim, Laila A"},{"full_name":"Abdel-Hadi, Sawsan S","last_name":"Abdel Hadi","first_name":"Sawsan"},{"last_name":"Marzouki","first_name":"Naima","full_name":"Marzouki, Naima"},{"full_name":"Ben-Omran, Tawfeg I","first_name":"Tawfeg","last_name":"Ben Omran"},{"last_name":"Al Saana","first_name":"Nouriya","full_name":"Al-Saana, Nouriya A"},{"full_name":"Sönmez, Fatma M","first_name":"Fatma","last_name":"Sönmez"},{"first_name":"Figen","last_name":"Celep","full_name":"Celep, Figen"},{"first_name":"Matloob","last_name":"Azam","full_name":"Azam, Matloob"},{"full_name":"Hill, Kiley J","first_name":"Kiley","last_name":"Hill"},{"full_name":"Collazo, Adrienne","first_name":"Adrienne","last_name":"Collazo"},{"first_name":"Ali","last_name":"Fenstermaker","full_name":"Fenstermaker, Ali G"},{"full_name":"Gaia Novarino","last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Akizu","first_name":"Naiara","full_name":"Akizu, Naiara"},{"full_name":"Garimella, Kiran V","last_name":"Garimella","first_name":"Kiran"},{"last_name":"Sougnez","first_name":"Carrie","full_name":"Sougnez, Carrie L"},{"full_name":"Russ, Carsten","first_name":"Carsten","last_name":"Russ"},{"full_name":"Gabriel, Stacey B","last_name":"Gabriel","first_name":"Stacey"},{"last_name":"Gleeson","first_name":"Joseph","full_name":"Gleeson, Joseph G"}],"volume":4,"date_created":"2018-12-11T11:56:56Z","date_updated":"2021-01-12T06:56:43Z","month":"06","day":"13","citation":{"ama":"Dixon Salazar T, Silhavy J, Udpa N, et al. Exome sequencing can improve diagnosis and alter patient management. Science Translational Medicine. 2012;4(138). doi:10.1126/scitranslmed.3003544","ista":"Dixon Salazar T, Silhavy J, Udpa N, Schroth J, Bielas S, Schaffer A, Olvera J, Bafna V, Zaki M, Abdel Salam G, Mansour L, Selim L, Abdel Hadi S, Marzouki N, Ben Omran T, Al Saana N, Sönmez F, Celep F, Azam M, Hill K, Collazo A, Fenstermaker A, Novarino G, Akizu N, Garimella K, Sougnez C, Russ C, Gabriel S, Gleeson J. 2012. Exome sequencing can improve diagnosis and alter patient management. Science Translational Medicine. 4(138).","ieee":"T. Dixon Salazar et al., “Exome sequencing can improve diagnosis and alter patient management,” Science Translational Medicine, vol. 4, no. 138. American Association for the Advancement of Science, 2012.","apa":"Dixon Salazar, T., Silhavy, J., Udpa, N., Schroth, J., Bielas, S., Schaffer, A., … Gleeson, J. (2012). Exome sequencing can improve diagnosis and alter patient management. Science Translational Medicine. American Association for the Advancement of Science. https://doi.org/10.1126/scitranslmed.3003544","mla":"Dixon Salazar, Tracy, et al. “Exome Sequencing Can Improve Diagnosis and Alter Patient Management.” Science Translational Medicine, vol. 4, no. 138, American Association for the Advancement of Science, 2012, doi:10.1126/scitranslmed.3003544.","short":"T. Dixon Salazar, J. Silhavy, N. Udpa, J. Schroth, S. Bielas, A. Schaffer, J. Olvera, V. Bafna, M. Zaki, G. Abdel Salam, L. Mansour, L. Selim, S. Abdel Hadi, N. Marzouki, T. Ben Omran, N. Al Saana, F. Sönmez, F. Celep, M. Azam, K. Hill, A. Collazo, A. Fenstermaker, G. Novarino, N. Akizu, K. Garimella, C. Sougnez, C. Russ, S. Gabriel, J. Gleeson, Science Translational Medicine 4 (2012).","chicago":"Dixon Salazar, Tracy, Jennifer Silhavy, Nitin Udpa, Jana Schroth, Stephanie Bielas, Ashleigh Schaffer, Jesus Olvera, et al. “Exome Sequencing Can Improve Diagnosis and Alter Patient Management.” Science Translational Medicine. American Association for the Advancement of Science, 2012. https://doi.org/10.1126/scitranslmed.3003544."},"publication":"Science Translational Medicine","quality_controlled":0,"date_published":"2012-06-13T00:00:00Z","doi":"10.1126/scitranslmed.3003544"},{"type":"journal_article","extern":1,"issue":"6105","publist_id":"4613","abstract":[{"text":"Autism spectrum disorders are a genetically heterogeneous constellation of syndromes characterized by impairments in reciprocal social interaction. Available somatic treatments have limited efficacy. We have identified inactivating mutations in the gene BCKDK (Branched Chain Ketoacid Dehydrogenase Kinase) in consanguineous families with autism, epilepsy, and intellectual disability. The encoded protein is responsible for phosphorylation-mediated inactivation of the E1α subunit of branched-chain ketoacid dehydrogenase (BCKDH). Patients with homozygous BCKDK mutations display reductions in BCKDK messenger RNA and protein, E1α phosphorylation, and plasma branched-chain amino acids. Bckdk knockout mice show abnormal brain amino acid profiles and neurobehavioral deficits that respond to dietary supplementation. Thus, autism presenting with intellectual disability and epilepsy caused by BCKDK mutations represents a potentially treatable syndrome.","lang":"eng"}],"intvolume":" 338","publisher":"American Association for the Advancement of Science","status":"public","publication_status":"published","title":"Mutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy","_id":"2314","year":"2012","volume":338,"date_created":"2018-12-11T11:56:56Z","date_updated":"2021-01-12T06:56:43Z","author":[{"full_name":"Gaia Novarino","first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178"},{"full_name":"El-Fishawy, Paul","last_name":"El Fishawy","first_name":"Paul"},{"first_name":"Hülya","last_name":"Kayserili","full_name":"Kayserili, Hülya"},{"full_name":"Meguid, Nagwa A","first_name":"Nagwa","last_name":"Meguid"},{"last_name":"Scott","first_name":"Eric","full_name":"Scott, Eric M"},{"last_name":"Schroth","first_name":"Jana","full_name":"Schroth, Jana"},{"full_name":"Silhavy, Jennifer L","first_name":"Jennifer","last_name":"Silhavy"},{"first_name":"Majdi","last_name":"Kara","full_name":"Kara, Majdi"},{"full_name":"Khalil, Rehab O","first_name":"Rehab","last_name":"Khalil"},{"last_name":"Ben Omran","first_name":"Tawfeg","full_name":"Ben-Omran, Tawfeg I"},{"full_name":"Ercan-Sencicek, Adife G","last_name":"Ercan Sencicek","first_name":"Adife"},{"full_name":"Hashish, Adel F","first_name":"Adel","last_name":"Hashish"},{"first_name":"Stephan","last_name":"Sanders","full_name":"Sanders, Stephan J"},{"full_name":"Gupta, Abha R","last_name":"Gupta","first_name":"Abha"},{"first_name":"Hebatalla","last_name":"Hashem","full_name":"Hashem, Hebatalla S"},{"full_name":"Matern, Dietrich","last_name":"Matern","first_name":"Dietrich"},{"full_name":"Gabriel, Stacey B","last_name":"Gabriel","first_name":"Stacey"},{"first_name":"Lawrence","last_name":"Sweetman","full_name":"Sweetman, Lawrence"},{"last_name":"Rahimi","first_name":"Yasmeen","full_name":"Rahimi, Yasmeen"},{"last_name":"Harris","first_name":"Robert","full_name":"Harris, Robert A"},{"full_name":"State, Matthew W","last_name":"State","first_name":"Matthew"},{"last_name":"Gleeson","first_name":"Joseph","full_name":"Gleeson, Joseph G"}],"month":"10","day":"19","page":"394 - 397","quality_controlled":0,"citation":{"chicago":"Novarino, Gaia, Paul El Fishawy, Hülya Kayserili, Nagwa Meguid, Eric Scott, Jana Schroth, Jennifer Silhavy, et al. “Mutations in BCKD-Kinase Lead to a Potentially Treatable Form of Autism with Epilepsy.” Science. American Association for the Advancement of Science, 2012. https://doi.org/10.1126/science.1224631.","short":"G. Novarino, P. El Fishawy, H. Kayserili, N. Meguid, E. Scott, J. Schroth, J. Silhavy, M. Kara, R. Khalil, T. Ben Omran, A. Ercan Sencicek, A. Hashish, S. Sanders, A. Gupta, H. Hashem, D. Matern, S. Gabriel, L. Sweetman, Y. Rahimi, R. Harris, M. State, J. Gleeson, Science 338 (2012) 394–397.","mla":"Novarino, Gaia, et al. “Mutations in BCKD-Kinase Lead to a Potentially Treatable Form of Autism with Epilepsy.” Science, vol. 338, no. 6105, American Association for the Advancement of Science, 2012, pp. 394–97, doi:10.1126/science.1224631.","ieee":"G. Novarino et al., “Mutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy,” Science, vol. 338, no. 6105. American Association for the Advancement of Science, pp. 394–397, 2012.","apa":"Novarino, G., El Fishawy, P., Kayserili, H., Meguid, N., Scott, E., Schroth, J., … Gleeson, J. (2012). Mutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.1224631","ista":"Novarino G, El Fishawy P, Kayserili H, Meguid N, Scott E, Schroth J, Silhavy J, Kara M, Khalil R, Ben Omran T, Ercan Sencicek A, Hashish A, Sanders S, Gupta A, Hashem H, Matern D, Gabriel S, Sweetman L, Rahimi Y, Harris R, State M, Gleeson J. 2012. Mutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy. Science. 338(6105), 394–397.","ama":"Novarino G, El Fishawy P, Kayserili H, et al. Mutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy. Science. 2012;338(6105):394-397. doi:10.1126/science.1224631"},"publication":"Science","doi":"10.1126/science.1224631","date_published":"2012-10-19T00:00:00Z"},{"day":"01","month":"01","publication":"Cell","citation":{"apa":"Novarino, G., Akizu, N., & Gleeson, J. (2011). Modeling human disease in humans: The ciliopathies. Cell. Cell Press. https://doi.org/10.1016/j.cell.2011.09.014","ieee":"G. Novarino, N. Akizu, and J. Gleeson, “Modeling human disease in humans: The ciliopathies,” Cell, vol. 147, no. 1. Cell Press, pp. 70–79, 2011.","ista":"Novarino G, Akizu N, Gleeson J. 2011. Modeling human disease in humans: The ciliopathies. Cell. 147(1), 70–79.","ama":"Novarino G, Akizu N, Gleeson J. Modeling human disease in humans: The ciliopathies. Cell. 2011;147(1):70-79. doi:10.1016/j.cell.2011.09.014","chicago":"Novarino, Gaia, Naiara Akizu, and Joseph Gleeson. “Modeling Human Disease in Humans: The Ciliopathies.” Cell. Cell Press, 2011. https://doi.org/10.1016/j.cell.2011.09.014.","short":"G. Novarino, N. Akizu, J. Gleeson, Cell 147 (2011) 70–79.","mla":"Novarino, Gaia, et al. “Modeling Human Disease in Humans: The Ciliopathies.” Cell, vol. 147, no. 1, Cell Press, 2011, pp. 70–79, doi:10.1016/j.cell.2011.09.014."},"quality_controlled":0,"page":"70 - 79","date_published":"2011-01-01T00:00:00Z","doi":"10.1016/j.cell.2011.09.014","type":"review","abstract":[{"lang":"eng","text":"Soon, the genetic basis of most human Mendelian diseases will be solved. The next challenge will be to leverage this information to uncover basic mechanisms of disease and develop new therapies. To understand how this transformation is already beginning to unfold, we focus on the ciliopathies, a class of multi-organ diseases caused by disruption of the primary cilium. Through a convergence of data involving mutant gene discovery, proteomics, and cell biology, more than a dozen phenotypically distinguishable conditions are now united as ciliopathies. Sitting at the interface between simple and complex genetic conditions, these diseases provide clues to the future direction of human genetics."}],"publist_id":"4615","issue":"1","extern":1,"year":"2011","_id":"2312","title":"Modeling human disease in humans: The ciliopathies","status":"public","publication_status":"published","publisher":"Cell Press","intvolume":" 147","author":[{"first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","full_name":"Gaia Novarino"},{"last_name":"Akizu","first_name":"Naiara","full_name":"Akizu, Naiara"},{"full_name":"Gleeson, Joseph G","last_name":"Gleeson","first_name":"Joseph"}],"date_updated":"2019-04-26T07:22:10Z","date_created":"2018-12-11T11:56:55Z","volume":147},{"year":"2010","_id":"2309","publisher":"Elsevier","status":"public","title":"The CLC family of chloride channels and transporters","publication_status":"published","author":[{"last_name":"Stauber","first_name":"Tobias","full_name":"Stauber, Tobias"},{"orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia","full_name":"Gaia Novarino"},{"full_name":"Jentsch, Thomas J","first_name":"Thomas","last_name":"Jentsch"}],"date_updated":"2021-01-12T06:56:41Z","date_created":"2018-12-11T11:56:54Z","type":"book_chapter","publist_id":"4616","abstract":[{"lang":"eng","text":"The importance of chloride ions in cell physiology has not been fully recognized until recently, in spite of the fact that chloride (Cl-), together with bicarbonate, is the most abundant free anion in animal cells, and performs or determines fundamental biological functions in all tissues. For many years it was thought that Cl- was distributed in thermodynamic equilibrium across the plasma membrane of most cells. Research carried out during the last couple of decades has led to a dramatic change in this simplistic view. We now know that most animal cells, neurons included, exhibit a non-equilibrium distribution of Cl- across their plasma membranes. Over the last 10 to 15 years, with the growth of molecular biology and the advent of new optical methods, an enormous amount of exciting new information has become available on the molecular structure and function of Cl- channels and carriers. In nerve cells, Cl- channels and carriers play key functional roles in GABA- and glycine-mediated synaptic inhibition, neuronal growth and development, extracellular potassium scavenging, sensory-transduction, neurotransmitter uptake and cell volume control. Disruption of Cl- homeostasis in neurons underlies pathological conditions such as epilepsy, deafness, imbalance, brain edema and ischemia, pain and neurogenic inflammation. This book is about how chloride ions are regulated and how they cross the plasma membrane of neurons. It spans from molecular structure and function of carriers and channels involved in Cl- transport to their role in various diseases. * The first comprehensive book on the structure, molecular biology, cell physiology, and role in diseases of chloride transporters / channels in the nervous system in almost 20 years * Chloride is the most abundant free anion in animal cells. THis book summarizes and integrates for the first time the important research of the past two decades that has shown that Cl- channels and carriers play key functional roles in GABA- and glycine-mediated synaptic inhibition, neuronal growth and development, extracellular potassium scavenging, sensory-transduction, neurotransmitter uptake and cell volume control. * The first book that systematically discusses the result of disruption of Cl- homeostasis in neurons which underlies pathological conditions such as epilepsy, deafness, imbalance, brain edema and ischemia, pain and neurogenic inflammation. * Spanning topics from molecular structure and function of carriers and channels involved in Cl- transport to their role in various diseases. * Involves all of the leading researchers in the field. * INcludes an extensive introductory section that covers basic thermodynamic and kinetics aspects of Cl- transport, as well as current methods for studying Cl- regulation, spanning from fluorescent dyes in single cells to knock-out models to make the book available for a growing population of graduate students and postdocs entering the field."}],"extern":1,"citation":{"mla":"Stauber, Tobias, et al. “The CLC Family of Chloride Channels and Transporters.” Physiology and Pathology of Chloride Transporters and Channels in the Nervous System, Elsevier, 2010, pp. 209–31, doi:10.1016/B978-0-12-374373-2.00012-1.","short":"T. Stauber, G. Novarino, T. Jentsch, in:, Physiology and Pathology of Chloride Transporters and Channels in the Nervous System, Elsevier, 2010, pp. 209–231.","chicago":"Stauber, Tobias, Gaia Novarino, and Thomas Jentsch. “The CLC Family of Chloride Channels and Transporters.” In Physiology and Pathology of Chloride Transporters and Channels in the Nervous System, 209–31. Elsevier, 2010. https://doi.org/10.1016/B978-0-12-374373-2.00012-1.","ama":"Stauber T, Novarino G, Jentsch T. The CLC family of chloride channels and transporters. In: Physiology and Pathology of Chloride Transporters and Channels in the Nervous System. Elsevier; 2010:209-231. doi:10.1016/B978-0-12-374373-2.00012-1","ista":"Stauber T, Novarino G, Jentsch T. 2010.The CLC family of chloride channels and transporters. In: Physiology and Pathology of chloride transporters and channels in the nervous system. , 209–231.","apa":"Stauber, T., Novarino, G., & Jentsch, T. (2010). The CLC family of chloride channels and transporters. In Physiology and Pathology of chloride transporters and channels in the nervous system (pp. 209–231). Elsevier. https://doi.org/10.1016/B978-0-12-374373-2.00012-1","ieee":"T. Stauber, G. Novarino, and T. Jentsch, “The CLC family of chloride channels and transporters,” in Physiology and Pathology of chloride transporters and channels in the nervous system, Elsevier, 2010, pp. 209–231."},"publication":"Physiology and Pathology of chloride transporters and channels in the nervous system","page":"209 - 231","quality_controlled":0,"date_published":"2010-01-01T00:00:00Z","doi":"10.1016/B978-0-12-374373-2.00012-1","month":"01","day":"01"},{"extern":1,"issue":"23","publist_id":"4618","abstract":[{"text":"Inactivation of the mainly endosomal 2Cl-/H+- exchanger ClC-5 severely impairs endocytosis in renal proximal tubules and underlies the human kidney stone disorder Dent's disease. In heterologous expression systems, interaction of the E3 ubiquitin ligasesWWP2and Nedd4-2 with a "PY-motif" in the cytoplasmic C terminus of ClC-5 stimulates its internalization from the plasma membrane and may influence receptor-mediated endocytosis. We asked whether this interaction is relevant in vivo and generated mice in which the PY-motif was destroyed by a point mutation. Unlike ClC-5 knock-out mice, these knock-in mice displayed neither low molecular weight proteinuria nor hyperphosphaturia, and both receptor-mediated and fluid-phase endocytosis were normal. The abundances and localizations of the endocytic receptor megalin and of the Na+-coupled phosphate transporter NaPi-2a (Npt2) were not changed, either. To explore whether the discrepancy in results from heterologous expression studies might be due to heteromerization of ClC-5 with ClC-3 or ClC-4 in vivo, we studied knock-in mice additionally deleted for those related transporters. Disruption of neither ClC-3 nor ClC-4 led to proteinuria or impaired proximal tubular endocytosis by itself, nor in combination with the PY-mutant of ClC-5. Endocytosis of cells lacking ClC-5 was not impaired further when ClC-3 or ClC-4 was additionally deleted. We conclude that ClC-5 is unique among CLC proteins in being crucial for proximal tubular endocytosis and that PY-motif-dependent ubiquitylation of ClC-5 is dispensable for this role.","lang":"eng"}],"type":"journal_article","volume":285,"date_created":"2018-12-11T11:56:55Z","date_updated":"2021-01-12T06:56:42Z","author":[{"full_name":"Rickheit, Gesa","last_name":"Rickheit","first_name":"Gesa"},{"full_name":"Wartosch, Lena","first_name":"Lena","last_name":"Wartosch"},{"full_name":"Schaffer, Sven","last_name":"Schaffer","first_name":"Sven"},{"last_name":"Stobrawa","first_name":"Sandra","full_name":"Stobrawa, Sandra M"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino","full_name":"Gaia Novarino"},{"last_name":"Weinert","first_name":"Stefanie","full_name":"Weinert, Stefanie"},{"last_name":"Jentsch","first_name":"Thomas","full_name":"Jentsch, Thomas J"}],"intvolume":" 285","publisher":"American Society for Biochemistry and Molecular Biology","title":"Role of ClC-5 in renal endocytosis is unique among ClC exchangers and does not require PY-motif-dependent ubiquitylation","status":"public","publication_status":"published","year":"2010","_id":"2311","day":"04","month":"06","date_published":"2010-06-04T00:00:00Z","doi":"10.1074/jbc.M110.115600","page":"17595 - 17603","quality_controlled":0,"citation":{"mla":"Rickheit, Gesa, et al. “Role of ClC-5 in Renal Endocytosis Is Unique among ClC Exchangers and Does Not Require PY-Motif-Dependent Ubiquitylation.” Journal of Biological Chemistry, vol. 285, no. 23, American Society for Biochemistry and Molecular Biology, 2010, pp. 17595–603, doi:10.1074/jbc.M110.115600.","short":"G. Rickheit, L. Wartosch, S. Schaffer, S. Stobrawa, G. Novarino, S. Weinert, T. Jentsch, Journal of Biological Chemistry 285 (2010) 17595–17603.","chicago":"Rickheit, Gesa, Lena Wartosch, Sven Schaffer, Sandra Stobrawa, Gaia Novarino, Stefanie Weinert, and Thomas Jentsch. “Role of ClC-5 in Renal Endocytosis Is Unique among ClC Exchangers and Does Not Require PY-Motif-Dependent Ubiquitylation.” Journal of Biological Chemistry. American Society for Biochemistry and Molecular Biology, 2010. https://doi.org/10.1074/jbc.M110.115600.","ama":"Rickheit G, Wartosch L, Schaffer S, et al. Role of ClC-5 in renal endocytosis is unique among ClC exchangers and does not require PY-motif-dependent ubiquitylation. Journal of Biological Chemistry. 2010;285(23):17595-17603. doi:10.1074/jbc.M110.115600","ista":"Rickheit G, Wartosch L, Schaffer S, Stobrawa S, Novarino G, Weinert S, Jentsch T. 2010. Role of ClC-5 in renal endocytosis is unique among ClC exchangers and does not require PY-motif-dependent ubiquitylation. Journal of Biological Chemistry. 285(23), 17595–17603.","apa":"Rickheit, G., Wartosch, L., Schaffer, S., Stobrawa, S., Novarino, G., Weinert, S., & Jentsch, T. (2010). Role of ClC-5 in renal endocytosis is unique among ClC exchangers and does not require PY-motif-dependent ubiquitylation. Journal of Biological Chemistry. American Society for Biochemistry and Molecular Biology. https://doi.org/10.1074/jbc.M110.115600","ieee":"G. Rickheit et al., “Role of ClC-5 in renal endocytosis is unique among ClC exchangers and does not require PY-motif-dependent ubiquitylation,” Journal of Biological Chemistry, vol. 285, no. 23. American Society for Biochemistry and Molecular Biology, pp. 17595–17603, 2010."},"publication":"Journal of Biological Chemistry"},{"quality_controlled":0,"page":"1398 - 1401","publication":"Science","citation":{"ista":"Novarino G, Weinert S, Rickheit G, Jentsch T. 2010. Endosomal chloride-proton exchange rather than chloride conductance is crucial for renal endocytosis. Science. 328(5984), 1398–1401.","ieee":"G. Novarino, S. Weinert, G. Rickheit, and T. Jentsch, “Endosomal chloride-proton exchange rather than chloride conductance is crucial for renal endocytosis,” Science, vol. 328, no. 5984. American Association for the Advancement of Science, pp. 1398–1401, 2010.","apa":"Novarino, G., Weinert, S., Rickheit, G., & Jentsch, T. (2010). Endosomal chloride-proton exchange rather than chloride conductance is crucial for renal endocytosis. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.1188070","ama":"Novarino G, Weinert S, Rickheit G, Jentsch T. Endosomal chloride-proton exchange rather than chloride conductance is crucial for renal endocytosis. Science. 2010;328(5984):1398-1401. doi:10.1126/science.1188070","chicago":"Novarino, Gaia, Stefanie Weinert, Gesa Rickheit, and Thomas Jentsch. “Endosomal Chloride-Proton Exchange Rather than Chloride Conductance Is Crucial for Renal Endocytosis.” Science. American Association for the Advancement of Science, 2010. https://doi.org/10.1126/science.1188070.","mla":"Novarino, Gaia, et al. “Endosomal Chloride-Proton Exchange Rather than Chloride Conductance Is Crucial for Renal Endocytosis.” Science, vol. 328, no. 5984, American Association for the Advancement of Science, 2010, pp. 1398–401, doi:10.1126/science.1188070.","short":"G. Novarino, S. Weinert, G. Rickheit, T. Jentsch, Science 328 (2010) 1398–1401."},"date_published":"2010-06-11T00:00:00Z","doi":"10.1126/science.1188070","day":"11","month":"06","status":"public","publication_status":"published","title":"Endosomal chloride-proton exchange rather than chloride conductance is crucial for renal endocytosis","publisher":"American Association for the Advancement of Science","intvolume":" 328","year":"2010","_id":"2310","date_updated":"2021-01-12T06:56:42Z","date_created":"2018-12-11T11:56:55Z","volume":328,"author":[{"full_name":"Gaia Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino"},{"full_name":"Weinert, Stefanie","first_name":"Stefanie","last_name":"Weinert"},{"full_name":"Rickheit, Gesa","last_name":"Rickheit","first_name":"Gesa"},{"last_name":"Jentsch","first_name":"Thomas","full_name":"Jentsch, Thomas J"}],"type":"journal_article","extern":1,"abstract":[{"lang":"eng","text":"Loss of the endosomal anion transport protein ClC-5 impairs renal endocytosis and underlies human Dent's disease. ClC-5 is thought to promote endocytosis by facilitating endosomal acidification through the neutralization of proton pump currents. However, ClC-5 is a 2 chloride (Cl-)/proton (H+) exchanger rather than a Cl- channel. We generated mice that carry the uncoupling E211A (unc) mutation that converts CLC-5 into a pure CL- conductor. Adenosine triphosphate (ATP)-dependent acidification of renal endosomes was reduced in mice in which ClC-5 was knocked out, but normal in Clcn5unc mice. However, their proximal tubular endocytosis was also impaired. Thus, endosomal chloride concentration, which is raised by CLC-5 in exchange for protons accumulated by the H+-ATPase, may play a role in endocytosis."}],"publist_id":"4617","issue":"5984"},{"doi":"10.1074/jbc.M412923200","date_published":"2005-05-13T00:00:00Z","quality_controlled":0,"page":"19177 - 19184","publication":"Journal of Biological Chemistry","citation":{"short":"J. Schwartz, G. Novarino, D. Piston, L. Defelice, Journal of Biological Chemistry 280 (2005) 19177–19184.","mla":"Schwartz, Joel, et al. “Substrate Binding Stoichiometry and Kinetics of the Norepinephrine Transporter.” Journal of Biological Chemistry, vol. 280, no. 19, American Society for Biochemistry and Molecular Biology, 2005, pp. 19177–84, doi:10.1074/jbc.M412923200.","chicago":"Schwartz, Joel, Gaia Novarino, David Piston, and Louis Defelice. “Substrate Binding Stoichiometry and Kinetics of the Norepinephrine Transporter.” Journal of Biological Chemistry. American Society for Biochemistry and Molecular Biology, 2005. https://doi.org/10.1074/jbc.M412923200.","ama":"Schwartz J, Novarino G, Piston D, Defelice L. Substrate binding stoichiometry and kinetics of the norepinephrine transporter. Journal of Biological Chemistry. 2005;280(19):19177-19184. doi:10.1074/jbc.M412923200","apa":"Schwartz, J., Novarino, G., Piston, D., & Defelice, L. (2005). Substrate binding stoichiometry and kinetics of the norepinephrine transporter. Journal of Biological Chemistry. American Society for Biochemistry and Molecular Biology. https://doi.org/10.1074/jbc.M412923200","ieee":"J. Schwartz, G. Novarino, D. Piston, and L. Defelice, “Substrate binding stoichiometry and kinetics of the norepinephrine transporter,” Journal of Biological Chemistry, vol. 280, no. 19. American Society for Biochemistry and Molecular Biology, pp. 19177–19184, 2005.","ista":"Schwartz J, Novarino G, Piston D, Defelice L. 2005. Substrate binding stoichiometry and kinetics of the norepinephrine transporter. Journal of Biological Chemistry. 280(19), 19177–19184."},"day":"13","month":"05","date_created":"2018-12-11T11:56:54Z","date_updated":"2021-01-12T06:56:40Z","volume":280,"author":[{"last_name":"Schwartz","first_name":"Joel","full_name":"Schwartz, Joel W"},{"first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","full_name":"Gaia Novarino"},{"full_name":"Piston, David W","last_name":"Piston","first_name":"David"},{"full_name":"DeFelice, Louis J","last_name":"Defelice","first_name":"Louis"}],"status":"public","publication_status":"published","title":"Substrate binding stoichiometry and kinetics of the norepinephrine transporter","intvolume":" 280","publisher":"American Society for Biochemistry and Molecular Biology","_id":"2307","year":"2005","extern":1,"abstract":[{"lang":"eng","text":"The human norepinephrine (NE) transporter (hNET) attenuates neuronal signaling by rapid NE clearance from the synaptic cleft, and NET is a target for cocaine and amphetamines as well as therapeutics for depression, obsessive-compulsive disorder, and post-traumatic stress disorder. In spite of its central importance in the nervous system, little is known about how NET substrates, such as NE, 1-methyl-4-tetrahydropyridinium (MPP+), or amphetamine, interact with NET at the molecular level. Nor do we understand the mechanisms behind the transport rate. Previously we introduced a fluorescent substrate similar to MPP+, which allowed separate and simultaneous binding and transport measurement (Schwartz, J. W., Blakely, R. D., and DeFelice, L. J. (2003) J. Biol. Chem. 278, 9768-9777). Here we use this substrate, 4-(4-(dimethylamino)styrl)-N-methyl-pyridinium (ASP+), in combination with green fluorescent protein-tagged hNETs to measure substrate-transporter stoichiometry and substrate binding kinetics. Calibrated confocal microscopy and fluorescence correlation spectroscopy reveal that hNETs, which are homo-multimers, bind one substrate molecule per transporter subunit. Substrate residence at the transporter, obtained from rapid on-off kinetics revealed in fluorescence correlation spectroscopy, is 526 μs. Substrate residence obtained by infinite dilution is 1000 times slower. This novel examination of substrate-transporter kinetics indicates that a single ASP + molecule binds and unbinds thousands of times before being transported or ultimately dissociated from hNET. Calibrated fluorescent images combined with mass spectroscopy give a transport rate of 0.06 ASP +/hNET-protein/s, thus 36,000 on-off binding events (and 36 actual departures) occur for one transport event. Therefore binding has a low probability of resulting in transport. We interpret these data to mean that inefficient binding could contribute to slow transport rates."}],"publist_id":"4619","issue":"19","type":"journal_article"},{"year":"2004","_id":"2308","publisher":"Society for Neuroscience","intvolume":" 24","title":"Involvement of the intracellular ion channel CLIC1 in microglia-mediated β-amyloid-induced neurotoxicity","publication_status":"published","status":"public","author":[{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino","full_name":"Gaia Novarino"},{"full_name":"Fabrizi, Cinzia","first_name":"Cinzia","last_name":"Fabrizi"},{"full_name":"Tonini, Raffaella","first_name":"Raffaella","last_name":"Tonini"},{"full_name":"Denti, Michela A","last_name":"Denti","first_name":"Michela"},{"first_name":"Albedi","last_name":"Malchiodi","full_name":"Malchiodi, Albedi F"},{"last_name":"Lauro","first_name":"Giuliana","full_name":"Lauro, Giuliana M"},{"full_name":"Sacchetti, Benedetto","first_name":"Benedetto","last_name":"Sacchetti"},{"first_name":"Silvia","last_name":"Paradisi","full_name":"Paradisi, Silvia"},{"full_name":"Ferroni, Arnaldo","last_name":"Ferroni","first_name":"Arnaldo"},{"full_name":"Curmi, Paul M G","last_name":"Curmi","first_name":"Paul"},{"full_name":"Breit, Samuel N","last_name":"Breit","first_name":"Samuel"},{"first_name":"Michele","last_name":"Mazzanti","full_name":"Mazzanti, Michele"}],"volume":24,"date_created":"2018-12-11T11:56:54Z","date_updated":"2021-01-12T06:56:41Z","type":"journal_article","publist_id":"4620","issue":"23","abstract":[{"text":"It is widely believed that the inflammatory events mediated by microglial activation contribute to several neurodegenerative processes. Alzheimer's disease, for example, is characterized by an accumulation of β-amyloid protein (Aβ) in neuritic plaques that are infiltrated by reactive microglia and astrocytes. Although Aβ and its fragment 25-35 exert a direct toxic effect on neurons, they also activate microglia. Microglial activation is accompanied by morphological changes, cell proliferation, and release of various cytokines and growth factors. A number of scientific reports suggest that the increased proliferation of microglial cells is dependent on ionic membrane currents and in particular on chloride conductances. An unusual chloride ion channel known to be associated with macrophage activation is the chloride intracellular channel-1 (CLIC1). Here we show that Aβ stimulation of neonatal rat microglia specifically leads to the increase in CLIC1 protein and to the functional expression of CLIC1 chloride conductance, both barely detectable on the plasma membrane of quiescent cells. CLIC1 protein expression in microglia increases after 24 hr of incubation with Aβ, simultaneously with the production of reactive nitrogen intermediates and of tumor necrosis factor-α (TNF-α). We demonstrate that reducing CLIC1 chloride conductance by a specific blocker [IAA-94 (R(+)-[(6,7-dichloro-2-cyclopentyl-2,3-dihydro-2-methyl-1-oxo-1H-inden-5yl)-oxy] acetic acid)] prevents neuronal apoptosis in neurons cocultured with Aβ-treated microglia. Furthermore, we show that small interfering RNAs used to knock down CLIC1 expression prevent TNF-α release induced by Aβ stimulation. These results provide a direct link between Aβ-induced microglial activation and CLIC1 functional expression.","lang":"eng"}],"extern":1,"citation":{"chicago":"Novarino, Gaia, Cinzia Fabrizi, Raffaella Tonini, Michela Denti, Albedi Malchiodi, Giuliana Lauro, Benedetto Sacchetti, et al. “Involvement of the Intracellular Ion Channel CLIC1 in Microglia-Mediated β-Amyloid-Induced Neurotoxicity.” Journal of Neuroscience. Society for Neuroscience, 2004. https://doi.org/10.1523/JNEUROSCI.1170-04.2004.","mla":"Novarino, Gaia, et al. “Involvement of the Intracellular Ion Channel CLIC1 in Microglia-Mediated β-Amyloid-Induced Neurotoxicity.” Journal of Neuroscience, vol. 24, no. 23, Society for Neuroscience, 2004, pp. 5322–30, doi:10.1523/JNEUROSCI.1170-04.2004.","short":"G. Novarino, C. Fabrizi, R. Tonini, M. Denti, A. Malchiodi, G. Lauro, B. Sacchetti, S. Paradisi, A. Ferroni, P. Curmi, S. Breit, M. Mazzanti, Journal of Neuroscience 24 (2004) 5322–5330.","ista":"Novarino G, Fabrizi C, Tonini R, Denti M, Malchiodi A, Lauro G, Sacchetti B, Paradisi S, Ferroni A, Curmi P, Breit S, Mazzanti M. 2004. Involvement of the intracellular ion channel CLIC1 in microglia-mediated β-amyloid-induced neurotoxicity. Journal of Neuroscience. 24(23), 5322–5330.","apa":"Novarino, G., Fabrizi, C., Tonini, R., Denti, M., Malchiodi, A., Lauro, G., … Mazzanti, M. (2004). Involvement of the intracellular ion channel CLIC1 in microglia-mediated β-amyloid-induced neurotoxicity. Journal of Neuroscience. Society for Neuroscience. https://doi.org/10.1523/JNEUROSCI.1170-04.2004","ieee":"G. Novarino et al., “Involvement of the intracellular ion channel CLIC1 in microglia-mediated β-amyloid-induced neurotoxicity,” Journal of Neuroscience, vol. 24, no. 23. Society for Neuroscience, pp. 5322–5330, 2004.","ama":"Novarino G, Fabrizi C, Tonini R, et al. Involvement of the intracellular ion channel CLIC1 in microglia-mediated β-amyloid-induced neurotoxicity. Journal of Neuroscience. 2004;24(23):5322-5330. doi:10.1523/JNEUROSCI.1170-04.2004"},"publication":"Journal of Neuroscience","page":"5322 - 5330","quality_controlled":0,"doi":"10.1523/JNEUROSCI.1170-04.2004","date_published":"2004-06-09T00:00:00Z","month":"06","day":"09"}]