[{"main_file_link":[{"url":"https://doi.org/10.1101/2024.02.15.580289","open_access":"1"}],"oa":1,"month":"02","abstract":[{"text":"The development, evolution, and function of the vertebrate central nervous system (CNS) can be best studied using diverse model organisms. Amphibians, with their unique phylogenetic position at the transition between aquatic and terrestrial lifestyles, are valuable for understanding the origin and evolution of the tetrapod brain and spinal cord. Their metamorphic developmental transitions and unique regenerative abilities also facilitate the discovery of mechanisms for neural circuit remodeling and replacement. The genetic toolkit for amphibians, however, remains limited, with only a few species having sequenced genomes and a small number of transgenic lines available. In mammals, recombinant adeno-associated viral vectors (AAVs) have become a powerful alternative to genome modification for visualizing and perturbing the nervous system. AAVs are DNA viruses that enable neuronal transduction in both developing and adult animals with low toxicity and spatial, temporal, and cell-type specificity. However, AAVs have never been shown to transduce amphibian cells efficiently. To bridge this gap, we established a simple, scalable, and robust strategy to screen AAV serotypes in three distantly-related amphibian species: the frogs Xenopus laevis and Pelophylax bedriagae, and the salamander Pleurodeles waltl, in both developing larval tadpoles and post-metamorphic animals. For each species, we successfully identified at least two AAV serotypes capable of infecting the CNS; however, no pan-amphibian serotype was identified, indicating rapid evolution of AAV tropism. In addition, we developed an AAV-based strategy that targets isochronic cohorts of developing neurons – a critical tool for parsing neural circuit assembly. Finally, to enable visualization and manipulation of neural circuits, we identified AAV variants for retrograde tracing of neuronal projections in adult animals. Our findings expand the toolkit for amphibians to include AAVs, establish a generalizable workflow for AAV screening in non-canonical research organisms, generate testable hypotheses for the evolution of AAV tropism, and lay the foundation for modern cross-species comparisons of vertebrate CNS development, function, and evolution. ","lang":"eng"}],"acknowledgement":"We would like to extend our thanks to members of the Sweeney, Tosches, Shein-Idelson,\r\nYamaguchi, Kelley, and Cline Labs for their contributions to this project, discussion and support.\r\nWe additionally thank the Beckman Institute Clover Center and Viviana Gradinaru (Caltech),\r\nKimberly Ritola (UNC NeuroTools), Flavia Gama Gomez Leite (ISTA Viral Core), and Hüseyin\r\nCihan Önal (Shigemoto Group, ISTA) for their consultation and assistance regarding AAVs, as\r\nwell as Andras Simon and Alberto Joven for feedback and discussions on AAVs in Pleurodeles.\r\nTo do these experiments, we have also benefited from the tremendous support of our animal care and imaging facilities at our respective institutions, as well as the amphibian stock centers\r\n(National Xenopus Resource Center, European Xenopus Resource Center, Xenopus Express)\r\nand our funding sources: U.S. National Science Foundation (NSF) Grant Number IOS 2110086\r\n(D.B.K., L.B.S., M.A.T., A.Y., and H.T.C.); United States-Israel Binational Science Foundation\r\n(BSF) Grant Number 2020702 (M.S.-I.); NSF Award Number 1645105 (G.J.G., M.E.H.); FTI\r\nStrategy Lower Austria Dissertation Grant Number FTI21-D-046 (D.V.); Horizon Europe ERC\r\nStarting Grant Number 101041551 (L.B.S.); NIH grant number R35GM146973 (M.A.T.); Rita Allen\r\nFoundation award number GA_032522_FE (M.A.T.); European Molecular Biology Organization\r\nLong-Term Fellowship ALTF 874-2021 (A.D.); National Science Foundation Graduate Research\r\nFellowship DGE 2036197 (E.C.J.B.); NIH grant number P40OD010997 (M.E.H).","oa_version":"Preprint","date_created":"2024-02-20T09:20:32Z","doi":"10.1101/2024.02.15.580289","date_published":"2024-02-16T00:00:00Z","publication_status":"submitted","year":"2024","publication":"bioRxiv","language":[{"iso":"eng"}],"day":"16","type":"preprint","status":"public","project":[{"_id":"bd73af52-d553-11ed-ba76-912049f0ac7a","name":"Entwicklung und Funktion der V1 Interneuronen vom Schwimmen zum Laufen während der Metamorphose von Xenopus","grant_number":"FTI21-D-046"},{"grant_number":"101041551","name":"Development and Evolution of Tetrapod Motor Circuits","_id":"ebb66355-77a9-11ec-83b8-b8ac210a4dae"}],"_id":"15016","article_processing_charge":"No","author":[{"full_name":"Jaeger, Eliza C.B.","last_name":"Jaeger","first_name":"Eliza C.B."},{"full_name":"Vijatovic, David","last_name":"Vijatovic","first_name":"David","id":"cf391e77-ec3c-11ea-a124-d69323410b58"},{"last_name":"Deryckere","full_name":"Deryckere, Astrid","first_name":"Astrid"},{"first_name":"Nikol","last_name":"Zorin","full_name":"Zorin, Nikol"},{"first_name":"Akemi L.","last_name":"Nguyen","full_name":"Nguyen, Akemi L."},{"last_name":"Ivanian","full_name":"Ivanian, Georgiy","id":"eaf2b366-cfd1-11ee-bbdf-c8790f800a05","first_name":"Georgiy"},{"first_name":"Jamie","full_name":"Woych, Jamie","last_name":"Woych"},{"last_name":"Arnold","full_name":"Arnold, Rebecca C","first_name":"Rebecca C","id":"d6cce458-14c9-11ed-a755-c1c8fc6fde6f"},{"last_name":"Ortega Gurrola","full_name":"Ortega Gurrola, Alonso","first_name":"Alonso"},{"full_name":"Shvartsman, Arik","last_name":"Shvartsman","first_name":"Arik"},{"full_name":"Barbieri, Francesca","last_name":"Barbieri","first_name":"Francesca","id":"a9492887-8972-11ed-ae7b-bfae10998254"},{"last_name":"Toma","full_name":"Toma, Florina-Alexandra","first_name":"Florina-Alexandra","id":"85dd99f2-15b2-11ec-abd3-d1ae4d57f3b5"},{"full_name":"Gorbsky, Gary J.","last_name":"Gorbsky","first_name":"Gary J."},{"first_name":"Marko E.","full_name":"Horb, Marko E.","last_name":"Horb"},{"first_name":"Hollis T.","full_name":"Cline, Hollis T.","last_name":"Cline"},{"last_name":"Shay","full_name":"Shay, Timothy F.","first_name":"Timothy F."},{"full_name":"Kelley, Darcy B.","last_name":"Kelley","first_name":"Darcy B."},{"first_name":"Ayako","full_name":"Yamaguchi, Ayako","last_name":"Yamaguchi"},{"first_name":"Mark","full_name":"Shein-Idelson, Mark","last_name":"Shein-Idelson"},{"first_name":"Maria Antonietta","last_name":"Tosches","full_name":"Tosches, Maria Antonietta"},{"id":"56BE8254-C4F0-11E9-8E45-0B23E6697425","first_name":"Lora Beatrice Jaeger","last_name":"Sweeney","full_name":"Sweeney, Lora Beatrice Jaeger","orcid":"0000-0001-9242-5601"}],"department":[{"_id":"LoSw"},{"_id":"MaDe"},{"_id":"GaNo"}],"title":"Adeno-associated viral tools to trace neural development and connectivity across amphibians","date_updated":"2024-02-20T09:34:25Z","citation":{"mla":"Jaeger, Eliza C. B., et al. “Adeno-Associated Viral Tools to Trace Neural Development and Connectivity across Amphibians.” BioRxiv, doi:10.1101/2024.02.15.580289.","short":"E.C.B. Jaeger, D. Vijatovic, A. Deryckere, N. Zorin, A.L. Nguyen, G. Ivanian, J. Woych, R.C. Arnold, A. Ortega Gurrola, A. Shvartsman, F. Barbieri, F.-A. Toma, G.J. Gorbsky, M.E. Horb, H.T. Cline, T.F. Shay, D.B. Kelley, A. Yamaguchi, M. Shein-Idelson, M.A. Tosches, L.B. Sweeney, BioRxiv (n.d.).","ieee":"E. C. B. Jaeger et al., “Adeno-associated viral tools to trace neural development and connectivity across amphibians,” bioRxiv. .","ama":"Jaeger ECB, Vijatovic D, Deryckere A, et al. Adeno-associated viral tools to trace neural development and connectivity across amphibians. bioRxiv. doi:10.1101/2024.02.15.580289","apa":"Jaeger, E. C. B., Vijatovic, D., Deryckere, A., Zorin, N., Nguyen, A. L., Ivanian, G., … Sweeney, L. B. (n.d.). Adeno-associated viral tools to trace neural development and connectivity across amphibians. bioRxiv. https://doi.org/10.1101/2024.02.15.580289","chicago":"Jaeger, Eliza C.B., David Vijatovic, Astrid Deryckere, Nikol Zorin, Akemi L. Nguyen, Georgiy Ivanian, Jamie Woych, et al. “Adeno-Associated Viral Tools to Trace Neural Development and Connectivity across Amphibians.” BioRxiv, n.d. https://doi.org/10.1101/2024.02.15.580289.","ista":"Jaeger ECB, Vijatovic D, Deryckere A, Zorin N, Nguyen AL, Ivanian G, Woych J, Arnold RC, Ortega Gurrola A, Shvartsman A, Barbieri F, Toma F-A, Gorbsky GJ, Horb ME, Cline HT, Shay TF, Kelley DB, Yamaguchi A, Shein-Idelson M, Tosches MA, Sweeney LB. Adeno-associated viral tools to trace neural development and connectivity across amphibians. bioRxiv, 10.1101/2024.02.15.580289."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"},{"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"}],"pmid":1,"oa_version":"None","scopus_import":"1","intvolume":" 80","month":"10","publication_status":"published","publication_identifier":{"eissn":["2168-6238"]},"language":[{"iso":"eng"}],"volume":80,"issue":"10","_id":"14443","article_type":"review","type":"journal_article","status":"public","date_updated":"2023-10-31T12:17:20Z","department":[{"_id":"GaNo"}],"quality_controlled":"1","publisher":"American Medical Association","year":"2023","publication":"JAMA Psychiatry","day":"01","page":"1066-1074","date_created":"2023-10-22T22:01:14Z","doi":"10.1001/jamapsychiatry.2023.2996","date_published":"2023-10-01T00:00:00Z","citation":{"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.","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","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","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.","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.","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.","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."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","external_id":{"pmid":["37610741"]},"article_processing_charge":"No","author":[{"last_name":"Schumann","full_name":"Schumann, Gunter","first_name":"Gunter"},{"full_name":"Andreassen, Ole A.","last_name":"Andreassen","first_name":"Ole A."},{"first_name":"Tobias","full_name":"Banaschewski, Tobias","last_name":"Banaschewski"},{"last_name":"Calhoun","full_name":"Calhoun, Vince D.","first_name":"Vince D."},{"first_name":"Nicholas","full_name":"Clinton, Nicholas","last_name":"Clinton"},{"last_name":"Desrivieres","full_name":"Desrivieres, Sylvane","first_name":"Sylvane"},{"first_name":"Ragnhild Eek","last_name":"Brandlistuen","full_name":"Brandlistuen, Ragnhild Eek"},{"first_name":"Jianfeng","full_name":"Feng, Jianfeng","last_name":"Feng"},{"full_name":"Hese, Soeren","last_name":"Hese","first_name":"Soeren"},{"first_name":"Esther","full_name":"Hitchen, Esther","last_name":"Hitchen"},{"first_name":"Per","full_name":"Hoffmann, Per","last_name":"Hoffmann"},{"last_name":"Jia","full_name":"Jia, Tianye","first_name":"Tianye"},{"first_name":"Viktor","last_name":"Jirsa","full_name":"Jirsa, Viktor"},{"last_name":"Marquand","full_name":"Marquand, Andre F.","first_name":"Andre F."},{"first_name":"Frauke","last_name":"Nees","full_name":"Nees, Frauke"},{"first_name":"Markus M.","last_name":"Nöthen","full_name":"Nöthen, Markus M."},{"full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia"},{"full_name":"Polemiti, Elli","last_name":"Polemiti","first_name":"Elli"},{"first_name":"Markus","last_name":"Ralser","full_name":"Ralser, Markus"},{"last_name":"Rapp","full_name":"Rapp, Michael","first_name":"Michael"},{"full_name":"Schepanski, Kerstin","last_name":"Schepanski","first_name":"Kerstin"},{"last_name":"Schikowski","full_name":"Schikowski, Tamara","first_name":"Tamara"},{"first_name":"Mel","full_name":"Slater, Mel","last_name":"Slater"},{"last_name":"Sommer","full_name":"Sommer, Peter","first_name":"Peter"},{"full_name":"Stahl, Bernd Carsten","last_name":"Stahl","first_name":"Bernd Carsten"},{"full_name":"Thompson, Paul M.","last_name":"Thompson","first_name":"Paul M."},{"full_name":"Twardziok, Sven","last_name":"Twardziok","first_name":"Sven"},{"first_name":"Dennis","full_name":"Van Der Meer, Dennis","last_name":"Van Der Meer"},{"last_name":"Walter","full_name":"Walter, Henrik","first_name":"Henrik"},{"last_name":"Westlye","full_name":"Westlye, Lars","first_name":"Lars"}],"title":"Addressing global environmental challenges to mental health using population neuroscience: A review"},{"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.","oa":1,"publisher":"Springer Nature","quality_controlled":"1","publication":"Nature Medicine","day":"15","year":"2023","isi":1,"has_accepted_license":"1","date_created":"2023-06-25T22:00:46Z","date_published":"2023-06-15T00:00:00Z","doi":"10.1038/s41591-023-02365-w","page":"1456-1467","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"ista":"Xu J, Liu N, Polemiti E, Garcia-Mondragon L, Tang J, Liu X, Lett T, Yu L, Nöthen MM, Feng J, Yu C, Marquand A, Schumann G, Walter H, Heinz A, Ralser M, Twardziok S, Vaidya N, Serin E, Jentsch M, Hitchen E, Eils R, Taron UH, Schütz T, Schepanski K, Banks J, Banaschewski T, Jansone K, Christmann N, Meyer-Lindenberg A, Tost H, Holz N, Schwarz E, Stringaris A, Neidhart M, Nees F, Siehl S, A. Andreassen O, T. Westlye L, Van Der Meer D, Fernandez S, Kjelkenes R, Ask H, Rapp M, Tschorn M, Böttger SJ, Novarino G, Marr L, Slater M, Viapiana GF, Orosa FE, Gallego J, Pastor A, Forstner A, Hoffmann P, M. Nöthen M, J. Forstner A, Claus I, Miller A, Heilmann-Heimbach S, Sommer P, Boye M, Wilbertz J, Schmitt K, Jirsa V, Petkoski S, Pitel S, Otten L, Athanasiadis AP, Pearmund C, Spanlang B, Alvarez E, Sanchez M, Giner A, Hese S, Renner P, Jia T, Gong Y, Xia Y, Chang X, Calhoun V, Liu J, Thompson P, Clinton N, Desrivieres S, H. Young A, Stahl B, Ogoh G. 2023. Effects of urban living environments on mental health in adults. Nature Medicine. 29, 1456–1467.","chicago":"Xu, Jiayuan, Nana Liu, Elli Polemiti, Liliana Garcia-Mondragon, Jie Tang, Xiaoxuan Liu, Tristram Lett, et al. “Effects of Urban Living Environments on Mental Health in Adults.” Nature Medicine. Springer Nature, 2023. https://doi.org/10.1038/s41591-023-02365-w.","short":"J. Xu, N. Liu, E. Polemiti, L. Garcia-Mondragon, J. Tang, X. Liu, T. Lett, L. Yu, M.M. Nöthen, J. Feng, C. Yu, A. Marquand, G. Schumann, H. Walter, A. Heinz, M. Ralser, S. Twardziok, N. Vaidya, E. Serin, M. Jentsch, E. Hitchen, R. Eils, U.H. Taron, T. Schütz, K. Schepanski, J. Banks, T. Banaschewski, K. Jansone, N. Christmann, A. Meyer-Lindenberg, H. Tost, N. Holz, E. Schwarz, A. Stringaris, M. Neidhart, F. Nees, S. Siehl, O. A. Andreassen, L. T. Westlye, D. Van Der Meer, S. Fernandez, R. Kjelkenes, H. Ask, M. Rapp, M. Tschorn, S.J. Böttger, G. Novarino, L. Marr, M. Slater, G.F. Viapiana, F.E. Orosa, J. Gallego, A. Pastor, A. Forstner, P. Hoffmann, M. M. Nöthen, A. J. Forstner, I. Claus, A. Miller, S. Heilmann-Heimbach, P. Sommer, M. Boye, J. Wilbertz, K. Schmitt, V. Jirsa, S. Petkoski, S. Pitel, L. Otten, A.P. Athanasiadis, C. Pearmund, B. Spanlang, E. Alvarez, M. Sanchez, A. Giner, S. Hese, P. Renner, T. Jia, Y. Gong, Y. Xia, X. Chang, V. Calhoun, J. Liu, P. Thompson, N. Clinton, S. Desrivieres, A. H. Young, B. Stahl, G. Ogoh, Nature Medicine 29 (2023) 1456–1467.","ieee":"J. Xu et al., “Effects of urban living environments on mental health in adults,” Nature Medicine, vol. 29. Springer Nature, pp. 1456–1467, 2023.","ama":"Xu J, Liu N, Polemiti E, et al. Effects of urban living environments on mental health in adults. Nature Medicine. 2023;29:1456-1467. doi:10.1038/s41591-023-02365-w","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","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."},"title":"Effects of urban living environments on mental health in adults","article_processing_charge":"No","external_id":{"isi":["001013172700001"]},"author":[{"first_name":"Jiayuan","full_name":"Xu, Jiayuan","last_name":"Xu"},{"full_name":"Liu, Nana","last_name":"Liu","first_name":"Nana"},{"first_name":"Elli","last_name":"Polemiti","full_name":"Polemiti, Elli"},{"first_name":"Liliana","last_name":"Garcia-Mondragon","full_name":"Garcia-Mondragon, Liliana"},{"full_name":"Tang, Jie","last_name":"Tang","first_name":"Jie"},{"first_name":"Xiaoxuan","full_name":"Liu, Xiaoxuan","last_name":"Liu"},{"full_name":"Lett, Tristram","last_name":"Lett","first_name":"Tristram"},{"first_name":"Le","last_name":"Yu","full_name":"Yu, Le"},{"first_name":"Markus M.","full_name":"Nöthen, Markus M.","last_name":"Nöthen"},{"first_name":"Jianfeng","last_name":"Feng","full_name":"Feng, Jianfeng"},{"full_name":"Yu, Chunshui","last_name":"Yu","first_name":"Chunshui"},{"full_name":"Marquand, Andre","last_name":"Marquand","first_name":"Andre"},{"last_name":"Schumann","full_name":"Schumann, Gunter","first_name":"Gunter"},{"first_name":"Henrik","last_name":"Walter","full_name":"Walter, Henrik"},{"full_name":"Heinz, Andreas","last_name":"Heinz","first_name":"Andreas"},{"last_name":"Ralser","full_name":"Ralser, Markus","first_name":"Markus"},{"first_name":"Sven","full_name":"Twardziok, Sven","last_name":"Twardziok"},{"full_name":"Vaidya, Nilakshi","last_name":"Vaidya","first_name":"Nilakshi"},{"full_name":"Serin, Emin","last_name":"Serin","first_name":"Emin"},{"first_name":"Marcel","full_name":"Jentsch, Marcel","last_name":"Jentsch"},{"last_name":"Hitchen","full_name":"Hitchen, Esther","first_name":"Esther"},{"full_name":"Eils, Roland","last_name":"Eils","first_name":"Roland"},{"first_name":"Ulrike Helene","full_name":"Taron, Ulrike Helene","last_name":"Taron"},{"first_name":"Tatjana","full_name":"Schütz, Tatjana","last_name":"Schütz"},{"first_name":"Kerstin","full_name":"Schepanski, Kerstin","last_name":"Schepanski"},{"full_name":"Banks, Jamie","last_name":"Banks","first_name":"Jamie"},{"full_name":"Banaschewski, Tobias","last_name":"Banaschewski","first_name":"Tobias"},{"first_name":"Karina","last_name":"Jansone","full_name":"Jansone, Karina"},{"first_name":"Nina","last_name":"Christmann","full_name":"Christmann, Nina"},{"first_name":"Andreas","full_name":"Meyer-Lindenberg, Andreas","last_name":"Meyer-Lindenberg"},{"first_name":"Heike","last_name":"Tost","full_name":"Tost, Heike"},{"full_name":"Holz, Nathalie","last_name":"Holz","first_name":"Nathalie"},{"full_name":"Schwarz, Emanuel","last_name":"Schwarz","first_name":"Emanuel"},{"last_name":"Stringaris","full_name":"Stringaris, Argyris","first_name":"Argyris"},{"first_name":"Maja","last_name":"Neidhart","full_name":"Neidhart, Maja"},{"first_name":"Frauke","last_name":"Nees","full_name":"Nees, Frauke"},{"last_name":"Siehl","full_name":"Siehl, Sebastian","first_name":"Sebastian"},{"last_name":"A. Andreassen","full_name":"A. Andreassen, Ole","first_name":"Ole"},{"last_name":"T. Westlye","full_name":"T. Westlye, Lars","first_name":"Lars"},{"first_name":"Dennis","last_name":"Van Der Meer","full_name":"Van Der Meer, Dennis"},{"first_name":"Sara","full_name":"Fernandez, Sara","last_name":"Fernandez"},{"first_name":"Rikka","last_name":"Kjelkenes","full_name":"Kjelkenes, Rikka"},{"first_name":"Helga","full_name":"Ask, Helga","last_name":"Ask"},{"full_name":"Rapp, Michael","last_name":"Rapp","first_name":"Michael"},{"last_name":"Tschorn","full_name":"Tschorn, Mira","first_name":"Mira"},{"full_name":"Böttger, Sarah Jane","last_name":"Böttger","first_name":"Sarah Jane"},{"first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino"},{"id":"4406F586-F248-11E8-B48F-1D18A9856A87","first_name":"Lena","last_name":"Marr","full_name":"Marr, Lena"},{"last_name":"Slater","full_name":"Slater, Mel","first_name":"Mel"},{"full_name":"Viapiana, Guillem Feixas","last_name":"Viapiana","first_name":"Guillem Feixas"},{"last_name":"Orosa","full_name":"Orosa, Francisco Eiroa","first_name":"Francisco Eiroa"},{"full_name":"Gallego, Jaime","last_name":"Gallego","first_name":"Jaime"},{"first_name":"Alvaro","last_name":"Pastor","full_name":"Pastor, Alvaro"},{"first_name":"Andreas","last_name":"Forstner","full_name":"Forstner, Andreas"},{"last_name":"Hoffmann","full_name":"Hoffmann, Per","first_name":"Per"},{"first_name":"Markus","full_name":"M. Nöthen, Markus","last_name":"M. Nöthen"},{"last_name":"J. Forstner","full_name":"J. Forstner, Andreas","first_name":"Andreas"},{"last_name":"Claus","full_name":"Claus, Isabelle","first_name":"Isabelle"},{"first_name":"Abbi","full_name":"Miller, Abbi","last_name":"Miller"},{"first_name":"Stefanie","last_name":"Heilmann-Heimbach","full_name":"Heilmann-Heimbach, Stefanie"},{"first_name":"Peter","last_name":"Sommer","full_name":"Sommer, Peter"},{"first_name":"Mona","full_name":"Boye, Mona","last_name":"Boye"},{"last_name":"Wilbertz","full_name":"Wilbertz, Johannes","first_name":"Johannes"},{"first_name":"Karen","last_name":"Schmitt","full_name":"Schmitt, Karen"},{"full_name":"Jirsa, Viktor","last_name":"Jirsa","first_name":"Viktor"},{"first_name":"Spase","last_name":"Petkoski","full_name":"Petkoski, Spase"},{"first_name":"Séverine","last_name":"Pitel","full_name":"Pitel, Séverine"},{"full_name":"Otten, Lisa","last_name":"Otten","first_name":"Lisa"},{"last_name":"Athanasiadis","full_name":"Athanasiadis, Anastasios Polykarpos","first_name":"Anastasios Polykarpos"},{"first_name":"Charlie","last_name":"Pearmund","full_name":"Pearmund, Charlie"},{"first_name":"Bernhard","last_name":"Spanlang","full_name":"Spanlang, Bernhard"},{"last_name":"Alvarez","full_name":"Alvarez, Elena","first_name":"Elena"},{"last_name":"Sanchez","full_name":"Sanchez, Mavi","first_name":"Mavi"},{"first_name":"Arantxa","full_name":"Giner, Arantxa","last_name":"Giner"},{"first_name":"Sören","full_name":"Hese, Sören","last_name":"Hese"},{"last_name":"Renner","full_name":"Renner, Paul","first_name":"Paul"},{"full_name":"Jia, Tianye","last_name":"Jia","first_name":"Tianye"},{"last_name":"Gong","full_name":"Gong, Yanting","first_name":"Yanting"},{"last_name":"Xia","full_name":"Xia, Yunman","first_name":"Yunman"},{"last_name":"Chang","full_name":"Chang, Xiao","first_name":"Xiao"},{"first_name":"Vince","full_name":"Calhoun, Vince","last_name":"Calhoun"},{"first_name":"Jingyu","full_name":"Liu, Jingyu","last_name":"Liu"},{"full_name":"Thompson, Paul","last_name":"Thompson","first_name":"Paul"},{"full_name":"Clinton, Nicholas","last_name":"Clinton","first_name":"Nicholas"},{"first_name":"Sylvane","last_name":"Desrivieres","full_name":"Desrivieres, Sylvane"},{"first_name":"Allan","last_name":"H. Young","full_name":"H. Young, Allan"},{"first_name":"Bernd","full_name":"Stahl, Bernd","last_name":"Stahl"},{"first_name":"George","last_name":"Ogoh","full_name":"Ogoh, George"}],"oa_version":"Published Version","abstract":[{"lang":"eng","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."}],"intvolume":" 29","month":"06","scopus_import":"1","language":[{"iso":"eng"}],"file":[{"file_name":"2023_NatureMedicine_Xu.pdf","date_created":"2023-06-26T10:15:44Z","creator":"dernst","file_size":7365360,"date_updated":"2023-06-26T10:15:44Z","success":1,"file_id":"13171","checksum":"bcd3225b2731c3442fa98987fd3bd46d","relation":"main_file","access_level":"open_access","content_type":"application/pdf"}],"publication_status":"published","publication_identifier":{"eissn":["1546-170X"],"issn":["1078-8956"]},"volume":29,"_id":"13168","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","article_type":"original","ddc":["570"],"date_updated":"2023-12-13T11:25:55Z","file_date_updated":"2023-06-26T10:15:44Z","department":[{"_id":"GaNo"}]},{"has_accepted_license":"1","isi":1,"year":"2023","day":"03","publication":"Frontiers in Psychiatry","date_published":"2023-10-03T00:00:00Z","doi":"10.3389/fpsyt.2023.1287879","date_created":"2023-10-29T23:01:16Z","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.","publisher":"Frontiers","quality_controlled":"1","oa":1,"citation":{"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.","short":"A. Narzisi, A. Halladay, G. Masi, G. Novarino, C. Lord, Frontiers in Psychiatry 14 (2023).","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.","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","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","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.","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."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","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","last_name":"Masi","first_name":"Gabriele"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178"},{"last_name":"Lord","full_name":"Lord, Catherine","first_name":"Catherine"}],"article_processing_charge":"Yes","external_id":{"isi":["001084841700001"],"pmid":["37854442"]},"title":"Tempering expectations: Considerations on the current state of stem cells therapy for autism treatment","article_number":"1287879","publication_identifier":{"eissn":["1664-0640"]},"publication_status":"published","file":[{"relation":"main_file","access_level":"open_access","content_type":"application/pdf","success":1,"file_id":"14468","checksum":"0a76373e9a4c0fc199f80380de257e86","creator":"dernst","file_size":147878,"date_updated":"2023-10-30T12:48:40Z","file_name":"2023_FrontiersPsychiatry_Narzisi.pdf","date_created":"2023-10-30T12:48:40Z"}],"language":[{"iso":"eng"}],"volume":14,"pmid":1,"oa_version":"Published Version","scopus_import":"1","month":"10","intvolume":" 14","date_updated":"2023-12-13T13:06:07Z","ddc":["570"],"file_date_updated":"2023-10-30T12:48:40Z","department":[{"_id":"GaNo"}],"_id":"14455","type":"journal_article","article_type":"letter_note","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public"},{"month":"08","intvolume":" 20","scopus_import":"1","main_file_link":[{"url":"https://doi.org/10.1038/s41592-023-01936-6","open_access":"1"}],"oa_version":"Published Version","pmid":1,"abstract":[{"lang":"eng","text":"Three-dimensional (3D) reconstruction of living brain tissue down to an individual synapse level would create opportunities for decoding the dynamics and structure–function relationships of the brain’s complex and dense information processing network; however, this has been hindered by insufficient 3D resolution, inadequate signal-to-noise ratio and prohibitive light burden in optical imaging, whereas electron microscopy is inherently static. Here we solved these challenges by developing an integrated optical/machine-learning technology, LIONESS (live information-optimized nanoscopy enabling saturated segmentation). This leverages optical modifications to stimulated emission depletion microscopy in comprehensively, extracellularly labeled tissue and previous information on sample structure via machine learning to simultaneously achieve isotropic super-resolution, high signal-to-noise ratio and compatibility with living tissue. This allows dense deep-learning-based instance segmentation and 3D reconstruction at a synapse level, incorporating molecular, activity and morphodynamic information. LIONESS opens up avenues for studying the dynamic functional (nano-)architecture of living brain tissue."}],"acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"E-Lib"},{"_id":"LifeSc"},{"_id":"M-Shop"}],"related_material":{"record":[{"status":"public","id":"12817","relation":"research_data"},{"status":"public","id":"14770","relation":"shorter_version"}],"link":[{"relation":"software","url":"https://github.com/danzllab/LIONESS"}]},"volume":20,"ec_funded":1,"language":[{"iso":"eng"}],"publication_identifier":{"issn":["1548-7091"],"eissn":["1548-7105"]},"publication_status":"published","status":"public","type":"journal_article","article_type":"original","_id":"13267","department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"},{"_id":"Bio"}],"date_updated":"2024-01-10T08:37:48Z","publisher":"Springer Nature","quality_controlled":"1","oa":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.).","doi":"10.1038/s41592-023-01936-6","date_published":"2023-08-01T00:00:00Z","date_created":"2023-07-23T22:01:13Z","page":"1256-1265","day":"01","publication":"Nature Methods","isi":1,"year":"2023","project":[{"call_identifier":"FWF","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","grant_number":"I03600","name":"Optical control of synaptic function via adhesion molecules"},{"name":"Molecular Drug Targets","grant_number":"W1232-B24","call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"The Wittgenstein Prize","grant_number":"Z00312"},{"name":"High content imaging to decode human immune cell interactions in health and allergic disease","_id":"23889792-32DE-11EA-91FC-C7463DDC885E"},{"grant_number":"665385","name":"International IST Doctoral Program","call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425"},{"call_identifier":"H2020","_id":"24F9549A-B435-11E9-9278-68D0E5697425","grant_number":"715767","name":"MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and Modeling"},{"grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"grant_number":"101026635","name":"Synaptic computations of the hippocampal CA3 circuitry","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","call_identifier":"H2020"},{"grant_number":"LT00057","name":"High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration","_id":"2668BFA0-B435-11E9-9278-68D0E5697425"}],"title":"Dense 4D nanoscale reconstruction of living brain tissue","author":[{"last_name":"Velicky","full_name":"Velicky, Philipp","orcid":"0000-0002-2340-7431","first_name":"Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Eder","id":"3FB91342-F248-11E8-B48F-1D18A9856A87","last_name":"Miguel Villalba","orcid":"0000-0001-5665-0430","full_name":"Miguel Villalba, Eder"},{"id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","first_name":"Julia M","orcid":"0000-0003-3862-1235","full_name":"Michalska, Julia M","last_name":"Michalska"},{"id":"46E28B80-F248-11E8-B48F-1D18A9856A87","first_name":"Julia","full_name":"Lyudchik, Julia","last_name":"Lyudchik"},{"first_name":"Donglai","last_name":"Wei","full_name":"Wei, Donglai"},{"first_name":"Zudi","last_name":"Lin","full_name":"Lin, Zudi"},{"last_name":"Watson","orcid":"0000-0002-8698-3823","full_name":"Watson, Jake","first_name":"Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E"},{"last_name":"Troidl","full_name":"Troidl, Jakob","first_name":"Jakob"},{"first_name":"Johanna","last_name":"Beyer","full_name":"Beyer, Johanna"},{"first_name":"Yoav","id":"43DF3136-F248-11E8-B48F-1D18A9856A87","full_name":"Ben Simon, Yoav","last_name":"Ben Simon"},{"orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","last_name":"Sommer","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","first_name":"Wiebke","full_name":"Jahr, Wiebke","last_name":"Jahr"},{"last_name":"Cenameri","full_name":"Cenameri, Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886","first_name":"Alban"},{"full_name":"Broichhagen, Johannes","last_name":"Broichhagen","first_name":"Johannes"},{"first_name":"Seth G.N.","full_name":"Grant, Seth G.N.","last_name":"Grant"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","last_name":"Jonas","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804"},{"last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Hanspeter","last_name":"Pfister","full_name":"Pfister, Hanspeter"},{"id":"49876194-F248-11E8-B48F-1D18A9856A87","first_name":"Bernd","orcid":"0000-0001-6511-9385","full_name":"Bickel, Bernd","last_name":"Bickel"},{"id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G","full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","last_name":"Danzl"}],"external_id":{"pmid":["37429995"],"isi":["001025621500001"]},"article_processing_charge":"Yes","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"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.","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","apa":"Velicky, P., Miguel Villalba, E., Michalska, J. M., Lyudchik, J., Wei, D., Lin, Z., … Danzl, J. G. (2023). Dense 4D nanoscale reconstruction of living brain tissue. Nature Methods. Springer Nature. https://doi.org/10.1038/s41592-023-01936-6","ieee":"P. Velicky et al., “Dense 4D nanoscale reconstruction of living brain tissue,” Nature Methods, vol. 20. Springer Nature, pp. 1256–1265, 2023.","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.","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.","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."}},{"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","citation":{"chicago":"Knaus, Lisa. “The Metabolism of the Developing Brain : How Large Neutral Amino Acids Modulate Perinatal Neuronal Excitability and Survival.” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/at:ista:13107.","ista":"Knaus L. 2023. The metabolism of the developing brain : How large neutral amino acids modulate perinatal neuronal excitability and survival. Institute of Science and Technology Austria.","mla":"Knaus, Lisa. The Metabolism of the Developing Brain : How Large Neutral Amino Acids Modulate Perinatal Neuronal Excitability and Survival. Institute of Science and Technology Austria, 2023, doi:10.15479/at:ista:13107.","apa":"Knaus, L. (2023). The metabolism of the developing brain : How large neutral amino acids modulate perinatal neuronal excitability and survival. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:13107","ama":"Knaus L. The metabolism of the developing brain : How large neutral amino acids modulate perinatal neuronal excitability and survival. 2023. doi:10.15479/at:ista:13107","ieee":"L. Knaus, “The metabolism of the developing brain : How large neutral amino acids modulate perinatal neuronal excitability and survival,” Institute of Science and Technology Austria, 2023.","short":"L. Knaus, The Metabolism of the Developing Brain : How Large Neutral Amino Acids Modulate Perinatal Neuronal Excitability and Survival, Institute of Science and Technology Austria, 2023."},"title":"The metabolism of the developing brain : How large neutral amino acids modulate perinatal neuronal excitability and survival","author":[{"last_name":"Knaus","full_name":"Knaus, Lisa","first_name":"Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87"}],"article_processing_charge":"No","project":[{"call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425","grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models"},{"name":"Molecular Drug Targets","grant_number":"W1232-B24","call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425"}],"day":"31","has_accepted_license":"1","year":"2023","doi":"10.15479/at:ista:13107","date_published":"2023-05-31T00:00:00Z","date_created":"2023-06-01T09:05:24Z","page":"147","publisher":"Institute of Science and Technology Austria","oa":1,"ddc":["570"],"supervisor":[{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"}],"date_updated":"2024-02-07T08:03:33Z","file_date_updated":"2023-06-07T08:41:49Z","department":[{"_id":"GradSch"},{"_id":"GaNo"}],"_id":"13107","status":"public","type":"dissertation","file":[{"access_level":"closed","relation":"source_file","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","file_id":"13112","checksum":"4b69a4ac0bbf4163d59c0b58dcb4f2c3","creator":"lknaus","date_updated":"2023-06-01T13:48:41Z","file_size":12991551,"date_created":"2023-06-01T13:48:41Z","file_name":"Thesis_Lisa Knaus_approved_final.docx"},{"access_level":"open_access","relation":"main_file","content_type":"application/pdf","file_id":"13114","checksum":"6903d152aa01181d87a696085af31c83","creator":"lknaus","date_updated":"2023-06-07T08:41:49Z","file_size":9309015,"date_created":"2023-06-02T09:47:29Z","file_name":"Thesis_Lisa Knaus_approved_final_pdfa2b.pdf"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["2663 - 337X"]},"degree_awarded":"PhD","publication_status":"published","related_material":{"record":[{"relation":"part_of_dissertation","id":"12802","status":"public"}]},"ec_funded":1,"oa_version":"Published Version","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"EM-Fac"}],"abstract":[{"text":"Within the human body, the brain exhibits the highest rate of energy consumption amongst all organs, with the majority of generated ATP being utilized to sustain neuronal activity. Therefore, the metabolism of the mature cerebral cortex is geared towards preserving metabolic homeostasis whilst generating significant amounts of energy. This requires a precise interplay between diverse metabolic pathways, spanning from a tissue-wide scale to the level of individual neurons. Disturbances to this delicate metabolic equilibrium, such as those resulting from maternal malnutrition\r\nor mutations affecting metabolic enzymes, often result in neuropathological variants of neurodevelopment. For instance, mutations in SLC7A5, a transporter of metabolically essential large neutral amino acids (LNAAs), have been associated with autism and microcephaly. However, despite recent progress in the field, the extent of metabolic restructuring that occurs within the developing brain and the corresponding alterations in nutrient demands during various critical periods remain largely unknown. To investigate this, we performed metabolomic profiling of the murine cerebral cortex to characterize the metabolic state of the forebrain at different developmental stages. We found that the developing cortex undergoes substantial metabolic reprogramming, with specific sets of metabolites displaying stage-specific changes. According to our observations, we determined a distinct temporal period in postnatal development during which the cortex displays heightened reliance on LNAAs. Hence, using a conditional knock-out mouse model, we deleted Slc7a5 in neural cells, allowing us to monitor the impact of a perturbed neuronal metabolic state across multiple developmental stages of corticogenesis. We found that manipulating the levels of essential LNAAs in cortical neurons in vivo affects one particular perinatal developmental period critical for cortical network refinement. Abnormally low intracellular LNAA levels result in cell-autonomous alterations in neuronal lipid metabolism, excitability, and survival during this particular time window. Although most of the effects of Slc7a5 deletion on neuronal physiology are transient, derailment of these processes during this brief but crucial window leads to long-term circuit dysfunction in mice. In conclusion, out data indicate that the cerebral cortex undergoes significant metabolic reorganization during development. This process involves the intricate integration of multiple metabolic pathways to ensure optimal neuronal function throughout different developmental stages. Our findings offer a paradigm for understanding how neurons synchronize the expression of nutrient-related genes with their activity to allow proper brain maturation. Further, our results demonstrate that disruptions in these precisely calibrated metabolic processes during critical periods of brain development may result in neuropathological outcomes in mice and in humans.","lang":"eng"}],"month":"05","alternative_title":["ISTA Thesis"]},{"date_updated":"2024-02-07T08:03:32Z","ddc":["570"],"file_date_updated":"2023-05-02T09:26:21Z","department":[{"_id":"SiHi"},{"_id":"GaNo"}],"_id":"12802","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","article_type":"original","keyword":["General Biochemistry","Genetics and Molecular Biology"],"status":"public","publication_status":"published","publication_identifier":{"issn":["0092-8674"]},"language":[{"iso":"eng"}],"file":[{"date_updated":"2023-05-02T09:26:21Z","file_size":15712841,"creator":"dernst","date_created":"2023-05-02T09:26:21Z","file_name":"2023_Cell_Knaus.pdf","content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"47e94fbe19e86505b429cb7a5b503ce6","file_id":"12889","success":1}],"ec_funded":1,"volume":186,"issue":"9","related_material":{"link":[{"description":"News on ISTA Website","url":"https://ista.ac.at/en/news/feed-them-or-lose-them/","relation":"press_release"}],"record":[{"relation":"dissertation_contains","id":"13107","status":"public"}]},"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"}],"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"EM-Fac"},{"_id":"Bio"},{"_id":"LifeSc"}],"oa_version":"Published Version","scopus_import":"1","intvolume":" 186","month":"04","citation":{"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.","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.","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.","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.","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","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"},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","external_id":{"isi":["000991468700001"]},"article_processing_charge":"Yes (via OA deal)","author":[{"full_name":"Knaus, Lisa","last_name":"Knaus","first_name":"Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","orcid":"0000-0003-1843-3173","full_name":"Basilico, Bernadette","last_name":"Basilico"},{"first_name":"Daniel","full_name":"Malzl, Daniel","last_name":"Malzl"},{"first_name":"Maria","last_name":"Gerykova Bujalkova","full_name":"Gerykova Bujalkova, Maria"},{"first_name":"Mateja","last_name":"Smogavec","full_name":"Smogavec, Mateja"},{"first_name":"Lena A.","last_name":"Schwarz","full_name":"Schwarz, Lena A."},{"id":"f141a35d-15a9-11ec-9fb2-fef6becc7b6f","first_name":"Sarah","full_name":"Gorkiewicz, Sarah","last_name":"Gorkiewicz"},{"id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","first_name":"Nicole","full_name":"Amberg, Nicole","orcid":"0000-0002-3183-8207","last_name":"Amberg"},{"first_name":"Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","last_name":"Pauler","full_name":"Pauler, Florian","orcid":"0000-0002-7462-0048"},{"first_name":"Christian","full_name":"Knittl-Frank, Christian","last_name":"Knittl-Frank"},{"full_name":"Tassinari, Marianna","last_name":"Tassinari","id":"7af593f1-d44a-11ed-bf94-a3646a6bb35e","first_name":"Marianna"},{"full_name":"Maulide, Nuno","last_name":"Maulide","first_name":"Nuno"},{"last_name":"Rülicke","full_name":"Rülicke, Thomas","first_name":"Thomas"},{"first_name":"Jörg","last_name":"Menche","full_name":"Menche, Jörg"},{"last_name":"Hippenmeyer","full_name":"Hippenmeyer, Simon","orcid":"0000-0003-2279-1061","id":"37B36620-F248-11E8-B48F-1D18A9856A87","first_name":"Simon"},{"first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino"}],"title":"Large neutral amino acid levels tune perinatal neuronal excitability and survival","project":[{"_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Molecular Drug Targets","grant_number":"W1232-B24"},{"_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780"},{"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","call_identifier":"H2020"}],"year":"2023","isi":1,"has_accepted_license":"1","publication":"Cell","day":"27","page":"1950-1967.e25","date_created":"2023-04-05T08:15:40Z","date_published":"2023-04-27T00:00:00Z","doi":"10.1016/j.cell.2023.02.037","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 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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."}],"acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"oa_version":"Published Version","month":"08","date_updated":"2024-02-21T12:18:19Z","ddc":["610"],"file_date_updated":"2023-08-04T13:19:47Z","department":[{"_id":"JoDa"},{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"Bio"},{"_id":"RySh"}],"_id":"13126","tmp":{"name":"Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)","image":"/images/cc_by_nc_sa.png","legal_code_url":"https://creativecommons.org/licenses/by-nc-sa/4.0/legalcode","short":"CC BY-NC-SA (4.0)"},"type":"research_data","status":"public","year":"2023","has_accepted_license":"1","day":"04","date_created":"2023-06-07T07:15:12Z","date_published":"2023-08-04T00:00:00Z","doi":"10.15479/AT:ISTA:13126","acknowledgement":"We thank Jakob Vorlaufer, Nathalie Agudelo-Dueñas, Wiebke Jahr, Andreas Wartak for microscope maintenance and troubleshooting, Caroline Kreuzinger, Anna Freeman, and Irene Erber for technical assistance and Matthias Tomschik for support with obtaining human samples. We gratefully acknowledge Eder Miguel for setting up webKnossos and Marek Šuplata for computational support and hardware control. We are grateful to Ryuichi Shigemoto and Bernd Bickel for generous support, and Michael Sixt and Scott Boyd (Stanford University) for discussions and critical reading of the manuscript. PSD95-HaloTag mice were kindly provided by Seth Grant (University of Edinburgh). We acknowledge expert support by IST Austria’s scientific computing, imaging and optics, preclinical, and lab support facilities, and by the Library and Miba machine shop.\r\nWe gratefully acknowledge funding by the following sources: \r\nAustrian Science Fund (FWF) grant I3600-B27 (JGD)\r\nAustrian Science Fund (FWF) grant DK W1232 (JGD, JMM)\r\nAustrian Science Fund (FWF) grant Z 312-B27, Wittgenstein award (PJ)\r\nAustrian Science Funds (FWF) projects I4685-B, I6565-B (SYNABS) and DOC 33-B27 (RH)\r\nGesellschaft für Forschungsförderung NÖ (NFB) grant LSC18-022 (JGD)\r\nEuropean Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 715508 – REVERSEAUTISM (GN)\r\nEuropean Union’s Horizon 2020 research and innovation programme, European Research Council (ERC) grant 692692 – GIANTSYN (PJ)\r\nMarie Skłodowska-Curie Actions Fellowship GA no. 665385 under the EU Horizon 2020 program (JMM, JL)\r\nMarie Skłodowska-Curie Actions Individual Fellowship 101026635 under the EU Horizon 2020 program (JFW)","oa":1,"publisher":"Institute of Science and Technology Austria","citation":{"apa":"Danzl, J. G. (2023). Research data for the publication “Imaging brain tissue architecture across millimeter to nanometer scales.” Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:13126","ama":"Danzl JG. Research data for the publication “Imaging brain tissue architecture across millimeter to nanometer scales.” 2023. doi:10.15479/AT:ISTA:13126","short":"J.G. Danzl, (2023).","ieee":"J. G. Danzl, “Research data for the publication ‘Imaging brain tissue architecture across millimeter to nanometer scales.’” Institute of Science and Technology Austria, 2023.","mla":"Danzl, Johann G. Research Data for the Publication “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” Institute of Science and Technology Austria, 2023, doi:10.15479/AT:ISTA:13126.","ista":"Danzl JG. 2023. Research data for the publication ‘Imaging brain tissue architecture across millimeter to nanometer scales’, Institute of Science and Technology Austria, 10.15479/AT:ISTA:13126.","chicago":"Danzl, Johann G. “Research Data for the Publication ‘Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.’” Institute of Science and Technology Austria, 2023. https://doi.org/10.15479/AT:ISTA:13126."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","article_processing_charge":"No","author":[{"first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","last_name":"Danzl","orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G"}],"title":"Research data for the publication \"Imaging brain tissue architecture across millimeter to nanometer scales\"","project":[{"grant_number":"I03600","name":"Optical control of synaptic function via adhesion molecules","call_identifier":"FWF","_id":"265CB4D0-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","_id":"26AA4EF2-B435-11E9-9278-68D0E5697425","name":"Molecular Drug Targets","grant_number":"W1232-B24"},{"grant_number":"Z00312","name":"The Wittgenstein Prize","_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"_id":"23889792-32DE-11EA-91FC-C7463DDC885E","name":"High content imaging to decode human immune cell interactions in health and allergic disease"},{"_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","grant_number":"715508"},{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse"},{"call_identifier":"H2020","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","name":"International IST Doctoral Program","grant_number":"665385"},{"call_identifier":"H2020","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","grant_number":"101026635","name":"Synaptic computations of the hippocampal CA3 circuitry"}]},{"status":"public","article_type":"original","type":"journal_article","_id":"14257","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"},{"_id":"Bio"},{"_id":"RySh"}],"date_updated":"2024-02-21T12:18:18Z","month":"08","scopus_import":"1","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1038/s41587-023-01911-8"}],"oa_version":"Published Version","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"LifeSc"},{"_id":"M-Shop"},{"_id":"E-Lib"}],"abstract":[{"text":"Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanometer synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS uses fixation-compatible extracellular labeling and optical imaging, including stimulated emission depletion or expansion microscopy, to comprehensively delineate cellular structures. It enables three-dimensional reconstruction of single synapses and mapping of synaptic connectivity by identification and analysis of putative synaptic cleft regions. Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed and quantified the synaptic input and output structure of identified neurons. We furthermore demonstrate applicability to clinically derived human tissue samples, including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing the cellular architecture of brain tissue in health and disease.","lang":"eng"}],"related_material":{"record":[{"id":"13126","status":"public","relation":"research_data"}],"link":[{"relation":"software","url":"https://github.com/danzllab/CATS"}]},"ec_funded":1,"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["1546-1696"],"issn":["1087-0156"]},"publication_status":"epub_ahead","project":[{"name":"Optical control of synaptic function via adhesion molecules","grant_number":"I03600","call_identifier":"FWF","_id":"265CB4D0-B435-11E9-9278-68D0E5697425"},{"grant_number":"W1232-B24","name":"Molecular Drug Targets","call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","name":"The Wittgenstein Prize","grant_number":"Z00312"},{"_id":"23889792-32DE-11EA-91FC-C7463DDC885E","name":"High content imaging to decode human immune cell interactions in health and allergic disease"},{"_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","grant_number":"715508"},{"_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692"},{"grant_number":"665385","name":"International IST Doctoral Program","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"name":"Synaptic computations of the hippocampal CA3 circuitry","grant_number":"101026635","call_identifier":"H2020","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9"}],"title":"Imaging brain tissue architecture across millimeter to nanometer scales","author":[{"last_name":"Michalska","full_name":"Michalska, Julia M","orcid":"0000-0003-3862-1235","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","first_name":"Julia M"},{"last_name":"Lyudchik","full_name":"Lyudchik, Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","first_name":"Julia"},{"id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","first_name":"Philipp","orcid":"0000-0002-2340-7431","full_name":"Velicky, Philipp","last_name":"Velicky"},{"first_name":"Hana","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","full_name":"Korinkova, Hana","last_name":"Korinkova"},{"last_name":"Watson","full_name":"Watson, Jake","orcid":"0000-0002-8698-3823","id":"63836096-4690-11EA-BD4E-32803DDC885E","first_name":"Jake"},{"full_name":"Cenameri, Alban","last_name":"Cenameri","first_name":"Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886"},{"orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","last_name":"Sommer","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Nicole","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-3183-8207","full_name":"Amberg, Nicole","last_name":"Amberg"},{"id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","first_name":"Alessandro","last_name":"Venturino","full_name":"Venturino, Alessandro","orcid":"0000-0003-2356-9403"},{"first_name":"Karl","last_name":"Roessler","full_name":"Roessler, Karl"},{"last_name":"Czech","full_name":"Czech, Thomas","first_name":"Thomas"},{"full_name":"Höftberger, Romana","last_name":"Höftberger","first_name":"Romana"},{"last_name":"Siegert","full_name":"Siegert, Sandra","orcid":"0000-0001-8635-0877","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","first_name":"Sandra"},{"first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino"},{"first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas"},{"full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G"}],"article_processing_charge":"Yes (in subscription journal)","external_id":{"isi":["001065254200001"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"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.","short":"J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri, C.M. Sommer, N. Amberg, A. Venturino, K. Roessler, T. Czech, R. Höftberger, S. Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, Nature Biotechnology (2023).","ieee":"J. M. Michalska 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","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.","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."},"publisher":"Springer Nature","quality_controlled":"1","oa":1,"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.).","doi":"10.1038/s41587-023-01911-8","date_published":"2023-08-31T00:00:00Z","date_created":"2023-09-03T22:01:15Z","day":"31","publication":"Nature Biotechnology","isi":1,"year":"2023"},{"status":"public","keyword":["Cellular and Molecular Neuroscience"],"article_type":"original","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"_id":"12140","department":[{"_id":"GaNo"}],"file_date_updated":"2023-01-24T09:16:29Z","ddc":["570"],"date_updated":"2023-08-04T08:56:10Z","month":"11","intvolume":" 16","scopus_import":"1","oa_version":"Published Version","pmid":1,"abstract":[{"text":"Microglia are dynamic cells, constantly surveying their surroundings and interacting with neurons and synapses. Indeed, a wealth of knowledge has revealed a critical role of microglia in modulating synaptic transmission and plasticity in the developing brain. In the past decade, novel pharmacological and genetic strategies have allowed the acute removal of microglia, opening the possibility to explore and understand the role of microglia also in the adult brain. In this review, we summarized and discussed the contribution of microglia depletion strategies to the current understanding of the role of microglia on synaptic function, learning and memory, and behavior both in physiological and pathological conditions. We first described the available microglia depletion methods highlighting their main strengths and weaknesses. We then reviewed the impact of microglia depletion on structural and functional synaptic plasticity. Next, we focused our analysis on the effects of microglia depletion on behavior, including general locomotor activity, sensory perception, motor function, sociability, learning and memory both in healthy animals and animal models of disease. Finally, we integrated the findings from the reviewed studies and discussed the emerging roles of microglia on the maintenance of synaptic function, learning, memory strength and forgetfulness, and the implications of microglia depletion in models of brain disease.","lang":"eng"}],"volume":16,"file":[{"date_updated":"2023-01-24T09:16:29Z","file_size":6399987,"creator":"dernst","date_created":"2023-01-24T09:16:29Z","file_name":"2022_FrontiersNeuroscience_Basilico.pdf","content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"84696213ecf99182c58a9f34b9ff2e23","file_id":"12352","success":1}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["1662-5102"]},"publication_status":"published","article_number":"1022431","title":"What microglia depletion approaches tell us about the role of microglia on synaptic function and behavior","author":[{"last_name":"Basilico","orcid":"0000-0003-1843-3173","full_name":"Basilico, Bernadette","first_name":"Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425"},{"full_name":"Ferrucci, Laura","last_name":"Ferrucci","first_name":"Laura"},{"first_name":"Azka","last_name":"Khan","full_name":"Khan, Azka"},{"full_name":"Di Angelantonio, Silvia","last_name":"Di Angelantonio","first_name":"Silvia"},{"first_name":"Davide","full_name":"Ragozzino, Davide","last_name":"Ragozzino"},{"first_name":"Ingrid","full_name":"Reverte, Ingrid","last_name":"Reverte"}],"external_id":{"isi":["000886526600001"],"pmid":["36406752"]},"article_processing_charge":"No","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"ista":"Basilico B, Ferrucci L, Khan A, Di Angelantonio S, Ragozzino D, Reverte I. 2022. What microglia depletion approaches tell us about the role of microglia on synaptic function and behavior. Frontiers in Cellular Neuroscience. 16, 1022431.","chicago":"Basilico, Bernadette, Laura Ferrucci, Azka Khan, Silvia Di Angelantonio, Davide Ragozzino, and Ingrid Reverte. “What Microglia Depletion Approaches Tell Us about the Role of Microglia on Synaptic Function and Behavior.” Frontiers in Cellular Neuroscience. Frontiers Media, 2022. https://doi.org/10.3389/fncel.2022.1022431.","ieee":"B. Basilico, L. Ferrucci, A. Khan, S. Di Angelantonio, D. Ragozzino, and I. Reverte, “What microglia depletion approaches tell us about the role of microglia on synaptic function and behavior,” Frontiers in Cellular Neuroscience, vol. 16. Frontiers Media, 2022.","short":"B. Basilico, L. Ferrucci, A. Khan, S. Di Angelantonio, D. Ragozzino, I. Reverte, Frontiers in Cellular Neuroscience 16 (2022).","ama":"Basilico B, Ferrucci L, Khan A, Di Angelantonio S, Ragozzino D, Reverte I. What microglia depletion approaches tell us about the role of microglia on synaptic function and behavior. Frontiers in Cellular Neuroscience. 2022;16. doi:10.3389/fncel.2022.1022431","apa":"Basilico, B., Ferrucci, L., Khan, A., Di Angelantonio, S., Ragozzino, D., & Reverte, I. (2022). What microglia depletion approaches tell us about the role of microglia on synaptic function and behavior. Frontiers in Cellular Neuroscience. Frontiers Media. https://doi.org/10.3389/fncel.2022.1022431","mla":"Basilico, Bernadette, et al. “What Microglia Depletion Approaches Tell Us about the Role of Microglia on Synaptic Function and Behavior.” Frontiers in Cellular Neuroscience, vol. 16, 1022431, Frontiers Media, 2022, doi:10.3389/fncel.2022.1022431."},"quality_controlled":"1","publisher":"Frontiers Media","oa":1,"acknowledgement":"The write-up of the review was supported by Sapienza University of Rome (Fondi di Ateneo, grant numbers #MA32117A7B698029 and #PH12017270934C3C to SD), Regione Lazio (POR FSE 2014/20, grant number #19036AP000000019 to SD), Fulbright 2019 (grant number\r\n#FSP-P005556 to SD), Institute Pasteur Italia (Fondi Cenci Bolognetti #363 to DR), and Network of European Funding for Neuroscience Research (ERA-NET NEURON Transnational\r\nResearch Projects on Neurodevelopmental Disorders 2021, grant acronym #JTC2021-SHANKAstro to DR).","date_published":"2022-11-04T00:00:00Z","doi":"10.3389/fncel.2022.1022431","date_created":"2023-01-12T12:04:50Z","day":"04","publication":"Frontiers in Cellular Neuroscience","isi":1,"has_accepted_license":"1","year":"2022"},{"date_updated":"2023-08-04T09:13:08Z","department":[{"_id":"GaNo"}],"_id":"12174","keyword":["Neurology (clinical)"],"status":"public","article_type":"original","type":"journal_article","language":[{"iso":"eng"}],"publication_status":"published","publication_identifier":{"issn":["0006-8950"],"eissn":["1460-2156"]},"ec_funded":1,"issue":"8","volume":145,"oa_version":"Published Version","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."}],"acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"LifeSc"}],"intvolume":" 145","month":"08","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1093/brain/awac145"}],"scopus_import":"1","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"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.","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.","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","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","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.","ista":"Guerrini R, Mei D, Szigeti MK, Pepe S, Koenig MK, Von Allmen G, Cho MT, McDonald K, Baker J, Bhambhani V, Powis Z, Rodan L, Nabbout R, Barcia G, Rosenfeld JA, Bacino CA, Mignot C, Power LH, Harris CJ, Marjanovic D, Møller RS, Hammer TB, Keski Filppula R, Vieira P, Hildebrandt C, Sacharow S, Maragliano L, Benfenati F, Lachlan K, Benneche A, Petit F, de Sainte Agathe JM, Hallinan B, Si Y, Wentzensen IM, Zou F, Narayanan V, Matsumoto N, Boncristiano A, la Marca G, Kato M, Anderson K, Barba C, Sturiale L, Garozzo D, Bei R, Masuelli L, Conti V, Novarino G, Fassio A. 2022. Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal homeostasis. Brain. 145(8), 2687–2703.","chicago":"Guerrini, Renzo, Davide Mei, Margit Katalin Szigeti, Sara Pepe, Mary Kay Koenig, Gretchen Von Allmen, Megan T Cho, et al. “Phenotypic and Genetic Spectrum of ATP6V1A Encephalopathy: A Disorder of Lysosomal Homeostasis.” Brain. Oxford University Press, 2022. https://doi.org/10.1093/brain/awac145."},"title":"Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal homeostasis","article_processing_charge":"No","external_id":{"isi":["000807770000001"]},"author":[{"full_name":"Guerrini, Renzo","last_name":"Guerrini","first_name":"Renzo"},{"last_name":"Mei","full_name":"Mei, Davide","first_name":"Davide"},{"first_name":"Margit Katalin","id":"44F4BDC0-F248-11E8-B48F-1D18A9856A87","last_name":"Szigeti","orcid":"0000-0001-9500-8758","full_name":"Szigeti, Margit Katalin"},{"last_name":"Pepe","full_name":"Pepe, Sara","first_name":"Sara"},{"last_name":"Koenig","full_name":"Koenig, Mary Kay","first_name":"Mary Kay"},{"full_name":"Von Allmen, Gretchen","last_name":"Von Allmen","first_name":"Gretchen"},{"first_name":"Megan T","full_name":"Cho, Megan T","last_name":"Cho"},{"first_name":"Kimberly","last_name":"McDonald","full_name":"McDonald, Kimberly"},{"last_name":"Baker","full_name":"Baker, Janice","first_name":"Janice"},{"first_name":"Vikas","last_name":"Bhambhani","full_name":"Bhambhani, Vikas"},{"first_name":"Zöe","full_name":"Powis, Zöe","last_name":"Powis"},{"last_name":"Rodan","full_name":"Rodan, Lance","first_name":"Lance"},{"first_name":"Rima","full_name":"Nabbout, Rima","last_name":"Nabbout"},{"first_name":"Giulia","full_name":"Barcia, Giulia","last_name":"Barcia"},{"first_name":"Jill A","last_name":"Rosenfeld","full_name":"Rosenfeld, Jill A"},{"first_name":"Carlos A","last_name":"Bacino","full_name":"Bacino, Carlos A"},{"first_name":"Cyril","last_name":"Mignot","full_name":"Mignot, Cyril"},{"full_name":"Power, Lillian H","last_name":"Power","first_name":"Lillian H"},{"first_name":"Catharine J","last_name":"Harris","full_name":"Harris, Catharine J"},{"first_name":"Dragan","last_name":"Marjanovic","full_name":"Marjanovic, Dragan"},{"full_name":"Møller, Rikke S","last_name":"Møller","first_name":"Rikke S"},{"first_name":"Trine B","full_name":"Hammer, Trine B","last_name":"Hammer"},{"full_name":"Keski Filppula, Riikka","last_name":"Keski Filppula","first_name":"Riikka"},{"full_name":"Vieira, Päivi","last_name":"Vieira","first_name":"Päivi"},{"last_name":"Hildebrandt","full_name":"Hildebrandt, Clara","first_name":"Clara"},{"full_name":"Sacharow, Stephanie","last_name":"Sacharow","first_name":"Stephanie"},{"first_name":"Luca","full_name":"Maragliano, Luca","last_name":"Maragliano"},{"full_name":"Benfenati, Fabio","last_name":"Benfenati","first_name":"Fabio"},{"last_name":"Lachlan","full_name":"Lachlan, Katherine","first_name":"Katherine"},{"first_name":"Andreas","last_name":"Benneche","full_name":"Benneche, Andreas"},{"full_name":"Petit, Florence","last_name":"Petit","first_name":"Florence"},{"first_name":"Jean Madeleine","full_name":"de Sainte Agathe, Jean Madeleine","last_name":"de Sainte Agathe"},{"last_name":"Hallinan","full_name":"Hallinan, Barbara","first_name":"Barbara"},{"first_name":"Yue","last_name":"Si","full_name":"Si, Yue"},{"last_name":"Wentzensen","full_name":"Wentzensen, Ingrid M","first_name":"Ingrid M"},{"first_name":"Fanggeng","last_name":"Zou","full_name":"Zou, Fanggeng"},{"first_name":"Vinodh","last_name":"Narayanan","full_name":"Narayanan, 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","last_name":"la Marca","first_name":"Giancarlo"},{"full_name":"Kato, Mitsuhiro","last_name":"Kato","first_name":"Mitsuhiro"},{"last_name":"Anderson","full_name":"Anderson, Kristin","first_name":"Kristin"},{"first_name":"Carmen","full_name":"Barba, Carmen","last_name":"Barba"},{"full_name":"Sturiale, Luisa","last_name":"Sturiale","first_name":"Luisa"},{"first_name":"Domenico","full_name":"Garozzo, Domenico","last_name":"Garozzo"},{"first_name":"Roberto","full_name":"Bei, Roberto","last_name":"Bei"},{"last_name":"Masuelli","full_name":"Masuelli, Laura","first_name":"Laura"},{"first_name":"Valerio","full_name":"Conti, Valerio","last_name":"Conti"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178"},{"last_name":"Fassio","full_name":"Fassio, Anna","first_name":"Anna"}],"project":[{"call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411"}],"publication":"Brain","day":"01","year":"2022","isi":1,"date_created":"2023-01-12T12:11:45Z","doi":"10.1093/brain/awac145","date_published":"2022-08-01T00:00:00Z","page":"2687-2703","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. ","oa":1,"publisher":"Oxford University Press","quality_controlled":"1"},{"year":"2022","has_accepted_license":"1","isi":1,"publication":"Frontiers in Oncology","day":"25","date_created":"2023-01-16T10:00:28Z","date_published":"2022-08-25T00:00:00Z","doi":"10.3389/fonc.2022.983507","acknowledgement":"The research leading to these results has received funding from AIRC under IG 2021 - ID. 26328 project – P.I. Cortese Barbara and AIRC under MFAG 2015 - ID. 16803 project – “P.I. Cortese Barbara”. The authors are also grateful to the ”Tecnopolo per la medicina di precisione” (TecnoMed Puglia) - Regione Puglia: DGR n.2117 del 21/11/2018, CUP: B84I18000540002 and “Tecnopolo di Nanotecnologia e Fotonica per la medicina di precisione” (TECNOMED) - FISR/MIUR-CNR: delibera CIPE n.3449 del 7-08-2017, CUP: B83B17000010001.\r\nWe thank Dr. Francesca Pagani for useful technical support. We thank also Irene Iacuitto, Giovanna Loffredo and Manuela Marchetti for practical administrative support.","oa":1,"quality_controlled":"1","publisher":"Frontiers Media","citation":{"mla":"Basilico, Bernadette, et al. “Substrate Stiffness Effect on Molecular Crosstalk of Epithelial-Mesenchymal Transition Mediators of Human Glioblastoma Cells.” Frontiers in Oncology, vol. 12, 983507, Frontiers Media, 2022, doi:10.3389/fonc.2022.983507.","apa":"Basilico, B., Palamà, I. E., D’Amone, S., Lauro, C., Rosito, M., Grieco, M., … Cortese, B. (2022). Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells. Frontiers in Oncology. Frontiers Media. https://doi.org/10.3389/fonc.2022.983507","ama":"Basilico B, Palamà IE, D’Amone S, et al. Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells. Frontiers in Oncology. 2022;12. doi:10.3389/fonc.2022.983507","short":"B. Basilico, I.E. Palamà, S. D’Amone, C. Lauro, M. Rosito, M. Grieco, P. Ratano, F. Cordella, C. Sanchini, S. Di Angelantonio, D. Ragozzino, M. Cascione, G. Gigli, B. Cortese, Frontiers in Oncology 12 (2022).","ieee":"B. Basilico et al., “Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells,” Frontiers in Oncology, vol. 12. Frontiers Media, 2022.","chicago":"Basilico, Bernadette, Ilaria Elena Palamà, Stefania D’Amone, Clotilde Lauro, Maria Rosito, Maddalena Grieco, Patrizia Ratano, et al. “Substrate Stiffness Effect on Molecular Crosstalk of Epithelial-Mesenchymal Transition Mediators of Human Glioblastoma Cells.” Frontiers in Oncology. Frontiers Media, 2022. https://doi.org/10.3389/fonc.2022.983507.","ista":"Basilico B, Palamà IE, D’Amone S, Lauro C, Rosito M, Grieco M, Ratano P, Cordella F, Sanchini C, Di Angelantonio S, Ragozzino D, Cascione M, Gigli G, Cortese B. 2022. Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells. Frontiers in Oncology. 12, 983507."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_processing_charge":"No","external_id":{"pmid":["36091138"],"isi":["000856524900001"]},"author":[{"full_name":"Basilico, Bernadette","orcid":"0000-0003-1843-3173","last_name":"Basilico","first_name":"Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425"},{"full_name":"Palamà, Ilaria Elena","last_name":"Palamà","first_name":"Ilaria Elena"},{"first_name":"Stefania","last_name":"D’Amone","full_name":"D’Amone, Stefania"},{"full_name":"Lauro, Clotilde","last_name":"Lauro","first_name":"Clotilde"},{"first_name":"Maria","last_name":"Rosito","full_name":"Rosito, Maria"},{"last_name":"Grieco","full_name":"Grieco, Maddalena","first_name":"Maddalena"},{"first_name":"Patrizia","last_name":"Ratano","full_name":"Ratano, Patrizia"},{"first_name":"Federica","last_name":"Cordella","full_name":"Cordella, Federica"},{"last_name":"Sanchini","full_name":"Sanchini, Caterina","first_name":"Caterina"},{"last_name":"Di Angelantonio","full_name":"Di Angelantonio, Silvia","first_name":"Silvia"},{"full_name":"Ragozzino, Davide","last_name":"Ragozzino","first_name":"Davide"},{"first_name":"Mariafrancesca","last_name":"Cascione","full_name":"Cascione, Mariafrancesca"},{"last_name":"Gigli","full_name":"Gigli, Giuseppe","first_name":"Giuseppe"},{"first_name":"Barbara","full_name":"Cortese, Barbara","last_name":"Cortese"}],"title":"Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells","article_number":"983507","publication_status":"published","publication_identifier":{"issn":["2234-943X"]},"language":[{"iso":"eng"}],"file":[{"date_created":"2023-01-30T10:25:21Z","file_name":"2022_FrontiersOntology_Basilico.pdf","creator":"dernst","date_updated":"2023-01-30T10:25:21Z","file_size":13588502,"checksum":"efc7edf9f626af31853790c5b598a68c","file_id":"12450","success":1,"access_level":"open_access","relation":"main_file","content_type":"application/pdf"}],"volume":12,"abstract":[{"text":"The complexity of the microenvironment effects on cell response, show accumulating evidence that glioblastoma (GBM) migration and invasiveness are influenced by the mechanical rigidity of their surroundings. The epithelial–mesenchymal transition (EMT) is a well-recognized driving force of the invasive behavior of cancer. However, the primary mechanisms of EMT initiation and progression remain unclear. We have previously showed that certain substrate stiffness can selectively stimulate human GBM U251-MG and GL15 glioblastoma cell lines motility. The present study unifies several known EMT mediators to uncover the reason of the regulation and response to these stiffnesses. Our results revealed that changing the rigidity of the mechanical environment tuned the response of both cell lines through change in morphological features, epithelial-mesenchymal markers (E-, N-Cadherin), EGFR and ROS expressions in an interrelated manner. Specifically, a stiffer microenvironment induced a mesenchymal cell shape, a more fragmented morphology, higher intracellular cytosolic ROS expression and lower mitochondrial ROS. Finally, we observed that cells more motile showed a more depolarized mitochondrial membrane potential. Unravelling the process that regulates GBM cells’ infiltrative behavior could provide new opportunities for identification of new targets and less invasive approaches for treatment.","lang":"eng"}],"oa_version":"Published Version","pmid":1,"scopus_import":"1","intvolume":" 12","month":"08","date_updated":"2023-08-04T09:54:16Z","ddc":["570"],"department":[{"_id":"GaNo"}],"file_date_updated":"2023-01-30T10:25:21Z","_id":"12268","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","article_type":"original","keyword":["Cancer Research","Oncology"],"status":"public"},{"acknowledgement":"The work was supported by a grant from MIUR (PRIN 2017HPTFFC_003) to Davide Ragozzino and in part by funds to Silvia Di Angelantonio (CrestOptics-IIT JointLab for Advanced Microscopy) and Daniele Caprioli (Istituto Pasteur-Fondazione Cenci Bolognetti). Bernadette Basilico, and Laura Ferrucci were supported by the PhD program in Clinical-Experimental Neuroscience and Psychiatry, Sapienza University, Rome; Caterina Sanchini was supported by the PhD program in Life Science, Sapienza University, Rome and by the Italian Institute of Technology, Rome. The authors thank Alessandro Felici, Claudia Valeri, Arsenio Armagno, and Senthilkumar Deivasigamani for help with animal husbandry and transgenic colonies management. They also wish to thank Piotr Bregestovski and Michal Schwartz for helpful discussions and criticism. PLX5622 was provided under Materials Transfer Agreement by Plexxikon Inc. (Berkeley, CA). Open Access Funding provided by Universita degli Studi di Roma La Sapienza within the CRUI-CARE Agreement.","oa":1,"quality_controlled":"1","publisher":"Wiley","publication":"Glia","day":"01","year":"2022","has_accepted_license":"1","isi":1,"date_created":"2022-03-04T08:53:37Z","doi":"10.1002/glia.24101","date_published":"2022-01-01T00:00:00Z","page":"173-195","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"apa":"Basilico, B., Ferrucci, L., Ratano, P., Golia, M. T., Grimaldi, A., Rosito, M., … Ragozzino, D. (2022). Microglia control glutamatergic synapses in the adult mouse hippocampus. Glia. Wiley. https://doi.org/10.1002/glia.24101","ama":"Basilico B, Ferrucci L, Ratano P, et al. Microglia control glutamatergic synapses in the adult mouse hippocampus. Glia. 2022;70(1):173-195. doi:10.1002/glia.24101","short":"B. Basilico, L. Ferrucci, P. Ratano, M.T. Golia, A. Grimaldi, M. Rosito, V. Ferretti, I. Reverte, C. Sanchini, M.C. Marrone, M. Giubettini, V. De Turris, D. Salerno, S. Garofalo, M. St‐Pierre, M. Carrier, M. Renzi, F. Pagani, B. Modi, M. Raspa, F. Scavizzi, C.T. Gross, S. Marinelli, M. Tremblay, D. Caprioli, L. Maggi, C. Limatola, S. Di Angelantonio, D. Ragozzino, Glia 70 (2022) 173–195.","ieee":"B. Basilico et al., “Microglia control glutamatergic synapses in the adult mouse hippocampus,” Glia, vol. 70, no. 1. Wiley, pp. 173–195, 2022.","mla":"Basilico, Bernadette, et al. “Microglia Control Glutamatergic Synapses in the Adult Mouse Hippocampus.” Glia, vol. 70, no. 1, Wiley, 2022, pp. 173–95, doi:10.1002/glia.24101.","ista":"Basilico B, Ferrucci L, Ratano P, Golia MT, Grimaldi A, Rosito M, Ferretti V, Reverte I, Sanchini C, Marrone MC, Giubettini M, De Turris V, Salerno D, Garofalo S, St‐Pierre M, Carrier M, Renzi M, Pagani F, Modi B, Raspa M, Scavizzi F, Gross CT, Marinelli S, Tremblay M, Caprioli D, Maggi L, Limatola C, Di Angelantonio S, Ragozzino D. 2022. Microglia control glutamatergic synapses in the adult mouse hippocampus. Glia. 70(1), 173–195.","chicago":"Basilico, Bernadette, Laura Ferrucci, Patrizia Ratano, Maria T. Golia, Alfonso Grimaldi, Maria Rosito, Valentina Ferretti, et al. “Microglia Control Glutamatergic Synapses in the Adult Mouse Hippocampus.” Glia. Wiley, 2022. https://doi.org/10.1002/glia.24101."},"title":"Microglia control glutamatergic synapses in the adult mouse hippocampus","external_id":{"isi":["000708025800001"],"pmid":["34661306"]},"article_processing_charge":"No","author":[{"id":"36035796-5ACA-11E9-A75E-7AF2E5697425","first_name":"Bernadette","orcid":"0000-0003-1843-3173","full_name":"Basilico, Bernadette","last_name":"Basilico"},{"first_name":"Laura","full_name":"Ferrucci, Laura","last_name":"Ferrucci"},{"first_name":"Patrizia","last_name":"Ratano","full_name":"Ratano, Patrizia"},{"first_name":"Maria T.","full_name":"Golia, Maria T.","last_name":"Golia"},{"first_name":"Alfonso","last_name":"Grimaldi","full_name":"Grimaldi, Alfonso"},{"first_name":"Maria","last_name":"Rosito","full_name":"Rosito, Maria"},{"first_name":"Valentina","last_name":"Ferretti","full_name":"Ferretti, Valentina"},{"full_name":"Reverte, Ingrid","last_name":"Reverte","first_name":"Ingrid"},{"first_name":"Caterina","last_name":"Sanchini","full_name":"Sanchini, Caterina"},{"full_name":"Marrone, Maria C.","last_name":"Marrone","first_name":"Maria C."},{"full_name":"Giubettini, Maria","last_name":"Giubettini","first_name":"Maria"},{"last_name":"De Turris","full_name":"De Turris, Valeria","first_name":"Valeria"},{"full_name":"Salerno, Debora","last_name":"Salerno","first_name":"Debora"},{"first_name":"Stefano","full_name":"Garofalo, Stefano","last_name":"Garofalo"},{"full_name":"St‐Pierre, Marie‐Kim","last_name":"St‐Pierre","first_name":"Marie‐Kim"},{"first_name":"Micael","last_name":"Carrier","full_name":"Carrier, Micael"},{"last_name":"Renzi","full_name":"Renzi, Massimiliano","first_name":"Massimiliano"},{"first_name":"Francesca","last_name":"Pagani","full_name":"Pagani, Francesca"},{"first_name":"Brijesh","full_name":"Modi, Brijesh","last_name":"Modi"},{"full_name":"Raspa, Marcello","last_name":"Raspa","first_name":"Marcello"},{"full_name":"Scavizzi, Ferdinando","last_name":"Scavizzi","first_name":"Ferdinando"},{"first_name":"Cornelius T.","full_name":"Gross, Cornelius T.","last_name":"Gross"},{"first_name":"Silvia","full_name":"Marinelli, Silvia","last_name":"Marinelli"},{"first_name":"Marie‐Ève","full_name":"Tremblay, Marie‐Ève","last_name":"Tremblay"},{"last_name":"Caprioli","full_name":"Caprioli, Daniele","first_name":"Daniele"},{"first_name":"Laura","last_name":"Maggi","full_name":"Maggi, Laura"},{"last_name":"Limatola","full_name":"Limatola, Cristina","first_name":"Cristina"},{"last_name":"Di Angelantonio","full_name":"Di Angelantonio, Silvia","first_name":"Silvia"},{"full_name":"Ragozzino, Davide","last_name":"Ragozzino","first_name":"Davide"}],"pmid":1,"oa_version":"Published Version","abstract":[{"text":"Microglia cells are active players in regulating synaptic development and plasticity in the brain. However, how they influence the normal functioning of synapses is largely unknown. In this study, we characterized the effects of pharmacological microglia depletion, achieved by administration of PLX5622, on hippocampal CA3-CA1 synapses of adult wild type mice. Following microglial depletion, we observed a reduction of spontaneous and evoked glutamatergic activity associated with a decrease of dendritic spine density. We also observed the appearance of immature synaptic features and higher levels of plasticity. Microglia depleted mice showed a deficit in the acquisition of the Novel Object Recognition task. These events were accompanied by hippocampal astrogliosis, although in the absence ofneuroinflammatory condition. PLX-induced synaptic changes were absent in Cx3cr1−/− mice, highlighting the role of CX3CL1/CX3CR1 axis in microglia control of synaptic functioning. Remarkably, microglia repopulation after PLX5622 withdrawal was associated with the recovery of hippocampal synapses and learning functions. Altogether, these data demonstrate that microglia contribute to normal synaptic functioning in the adult brain and that their removal induces reversible changes in organization and activity of glutamatergic synapses.","lang":"eng"}],"intvolume":" 70","month":"01","scopus_import":"1","language":[{"iso":"eng"}],"file":[{"file_id":"10819","checksum":"f10a897290e66c0a062e04ba91db6c17","success":1,"content_type":"application/pdf","access_level":"open_access","relation":"main_file","date_created":"2022-03-04T08:55:27Z","file_name":"2021_Glia_Basilico.pdf","date_updated":"2022-03-04T08:55:27Z","file_size":5340294,"creator":"dernst"}],"publication_status":"published","publication_identifier":{"eissn":["1098-1136"],"issn":["0894-1491"]},"issue":"1","volume":70,"_id":"10818","keyword":["Cellular and Molecular Neuroscience","Neurology"],"status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","image":"/images/cc_by_nc.png","name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","short":"CC BY-NC (4.0)"},"article_type":"original","type":"journal_article","ddc":["570"],"date_updated":"2023-09-05T16:01:23Z","department":[{"_id":"GaNo"}],"file_date_updated":"2022-03-04T08:55:27Z"},{"department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"}],"title":"Saturated reconstruction of living brain tissue","author":[{"last_name":"Velicky","full_name":"Velicky, Philipp","orcid":"0000-0002-2340-7431","first_name":"Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Miguel Villalba","full_name":"Miguel Villalba, Eder","orcid":"0000-0001-5665-0430","id":"3FB91342-F248-11E8-B48F-1D18A9856A87","first_name":"Eder"},{"first_name":"Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3862-1235","full_name":"Michalska, Julia M","last_name":"Michalska"},{"first_name":"Donglai","full_name":"Wei, Donglai","last_name":"Wei"},{"last_name":"Lin","full_name":"Lin, Zudi","first_name":"Zudi"},{"first_name":"Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E","last_name":"Watson","orcid":"0000-0002-8698-3823","full_name":"Watson, Jake"},{"full_name":"Troidl, Jakob","last_name":"Troidl","first_name":"Jakob"},{"full_name":"Beyer, Johanna","last_name":"Beyer","first_name":"Johanna"},{"last_name":"Ben Simon","full_name":"Ben Simon, Yoav","first_name":"Yoav","id":"43DF3136-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Sommer","full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M"},{"full_name":"Jahr, Wiebke","last_name":"Jahr","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","first_name":"Wiebke"},{"id":"9ac8f577-2357-11eb-997a-e566c5550886","first_name":"Alban","last_name":"Cenameri","full_name":"Cenameri, Alban"},{"first_name":"Johannes","last_name":"Broichhagen","full_name":"Broichhagen, Johannes"},{"first_name":"Seth G. N.","last_name":"Grant","full_name":"Grant, Seth G. N."},{"first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","last_name":"Jonas","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804"},{"orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia"},{"first_name":"Hanspeter","full_name":"Pfister, Hanspeter","last_name":"Pfister"},{"orcid":"0000-0001-6511-9385","full_name":"Bickel, Bernd","last_name":"Bickel","first_name":"Bernd","id":"49876194-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","last_name":"Danzl"}],"article_processing_charge":"No","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_updated":"2024-03-27T23:30:20Z","citation":{"short":"P. Velicky, E. Miguel Villalba, J.M. Michalska, D. Wei, Z. Lin, J. Watson, J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri, J. Broichhagen, S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel, J.G. Danzl, BioRxiv (n.d.).","ieee":"P. Velicky et al., “Saturated reconstruction of living brain tissue,” bioRxiv. Cold Spring Harbor Laboratory.","ama":"Velicky P, Miguel Villalba E, Michalska JM, et al. Saturated reconstruction of living brain tissue. bioRxiv. doi:10.1101/2022.03.16.484431","apa":"Velicky, P., Miguel Villalba, E., Michalska, J. M., Wei, D., Lin, Z., Watson, J., … Danzl, J. G. (n.d.). Saturated reconstruction of living brain tissue. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2022.03.16.484431","mla":"Velicky, Philipp, et al. “Saturated Reconstruction of Living Brain Tissue.” BioRxiv, Cold Spring Harbor Laboratory, 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.","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."},"status":"public","type":"preprint","_id":"11943","date_published":"2022-05-09T00:00:00Z","related_material":{"record":[{"status":"public","id":"12470","relation":"dissertation_contains"}]},"doi":"10.1101/2022.03.16.484431","date_created":"2022-08-23T11:07:59Z","day":"09","publication":"bioRxiv","language":[{"iso":"eng"}],"publication_status":"submitted","year":"2022","month":"05","publisher":"Cold Spring Harbor Laboratory","oa":1,"main_file_link":[{"url":"https://doi.org/10.1101/2022.03.16.484431","open_access":"1"}],"oa_version":"Preprint","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."}]},{"_id":"11950","status":"public","type":"preprint","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","date_updated":"2024-03-27T23:30:20Z","citation":{"apa":"Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri, A., … Danzl, J. G. (n.d.). Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2022.08.17.504272","ama":"Michalska JM, Lyudchik J, Velicky P, et al. Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv. doi:10.1101/2022.08.17.504272","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.).","ieee":"J. M. Michalska et al., “Uncovering brain tissue architecture across scales with super-resolution light microscopy,” bioRxiv. Cold Spring Harbor Laboratory.","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.","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.","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."},"title":"Uncovering brain tissue architecture across scales with super-resolution light microscopy","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"}],"author":[{"full_name":"Michalska, Julia M","orcid":"0000-0003-3862-1235","last_name":"Michalska","first_name":"Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","last_name":"Lyudchik","full_name":"Lyudchik, Julia"},{"last_name":"Velicky","full_name":"Velicky, Philipp","orcid":"0000-0002-2340-7431","first_name":"Philipp","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87"},{"id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed","first_name":"Hana","full_name":"Korinkova, Hana","last_name":"Korinkova"},{"first_name":"Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E","full_name":"Watson, Jake","orcid":"0000-0002-8698-3823","last_name":"Watson"},{"full_name":"Cenameri, Alban","last_name":"Cenameri","id":"9ac8f577-2357-11eb-997a-e566c5550886","first_name":"Alban"},{"orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","last_name":"Sommer","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0003-2356-9403","full_name":"Venturino, Alessandro","last_name":"Venturino","first_name":"Alessandro","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Roessler","full_name":"Roessler, Karl","first_name":"Karl"},{"last_name":"Czech","full_name":"Czech, Thomas","first_name":"Thomas"},{"first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8635-0877","full_name":"Siegert, Sandra","last_name":"Siegert"},{"last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia"},{"full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas","id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M"},{"id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G","last_name":"Danzl","full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973"}],"article_processing_charge":"No","oa_version":"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"}],"month":"08","publisher":"Cold Spring Harbor Laboratory","oa":1,"main_file_link":[{"url":"https://doi.org/10.1101/2022.08.17.504272","open_access":"1"}],"day":"18","publication":"bioRxiv","language":[{"iso":"eng"}],"publication_status":"submitted","year":"2022","related_material":{"record":[{"relation":"dissertation_contains","status":"public","id":"12470"}]},"doi":"10.1101/2022.08.17.504272","date_published":"2022-08-18T00:00:00Z","date_created":"2022-08-24T08:24:52Z"},{"article_number":"110615","project":[{"grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"name":"Identification of converging Molecular Pathways Across Chromatinopathies as Targets for Therapy","grant_number":"I04205","_id":"2690FEAC-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"ista":"Villa CE, Cheroni C, Dotter C, López-Tóbon A, Oliveira B, Sacco R, Yahya AÇ, Morandell J, Gabriele M, Tavakoli M, Lyudchik J, Sommer CM, Gabitto M, Danzl JG, Testa G, Novarino G. 2022. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. Cell Reports. 39(1), 110615.","chicago":"Villa, Carlo Emanuele, Cristina Cheroni, Christoph Dotter, Alejandro López-Tóbon, Bárbara Oliveira, Roberto Sacco, Aysan Çerağ Yahya, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” Cell Reports. Elsevier, 2022. https://doi.org/10.1016/j.celrep.2022.110615.","apa":"Villa, C. E., Cheroni, C., Dotter, C., López-Tóbon, A., Oliveira, B., Sacco, R., … Novarino, G. (2022). CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. Cell Reports. Elsevier. https://doi.org/10.1016/j.celrep.2022.110615","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","short":"C.E. Villa, C. Cheroni, C. Dotter, A. López-Tóbon, B. Oliveira, R. Sacco, A.Ç. Yahya, J. Morandell, M. Gabriele, M. Tavakoli, J. Lyudchik, C.M. Sommer, M. Gabitto, J.G. Danzl, G. Testa, G. Novarino, Cell Reports 39 (2022).","ieee":"C. E. Villa 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."},"title":"CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories","author":[{"last_name":"Villa","full_name":"Villa, Carlo Emanuele","first_name":"Carlo Emanuele"},{"full_name":"Cheroni, Cristina","last_name":"Cheroni","first_name":"Cristina"},{"id":"4C66542E-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph","full_name":"Dotter, Christoph","orcid":"0000-0002-9033-9096","last_name":"Dotter"},{"first_name":"Alejandro","last_name":"López-Tóbon","full_name":"López-Tóbon, Alejandro"},{"last_name":"Oliveira","full_name":"Oliveira, Bárbara","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","first_name":"Bárbara"},{"full_name":"Sacco, Roberto","last_name":"Sacco","first_name":"Roberto","id":"42C9F57E-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Yahya","full_name":"Yahya, Aysan Çerağ","id":"365A65F8-F248-11E8-B48F-1D18A9856A87","first_name":"Aysan Çerağ"},{"last_name":"Morandell","full_name":"Morandell, Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","first_name":"Jasmin"},{"full_name":"Gabriele, Michele","last_name":"Gabriele","first_name":"Michele"},{"id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87","first_name":"Mojtaba","last_name":"Tavakoli","orcid":"0000-0002-7667-6854","full_name":"Tavakoli, Mojtaba"},{"id":"46E28B80-F248-11E8-B48F-1D18A9856A87","first_name":"Julia","last_name":"Lyudchik","full_name":"Lyudchik, Julia"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M","full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","last_name":"Sommer"},{"first_name":"Mariano","last_name":"Gabitto","full_name":"Gabitto, Mariano"},{"orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G","last_name":"Danzl","first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Giuseppe","full_name":"Testa, Giuseppe","last_name":"Testa"},{"full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia"}],"external_id":{"pmid":["35385734"],"isi":["000785983900003"]},"article_processing_charge":"Yes","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.","publisher":"Elsevier","quality_controlled":"1","oa":1,"day":"05","publication":"Cell Reports","has_accepted_license":"1","isi":1,"year":"2022","date_published":"2022-04-05T00:00:00Z","doi":"10.1016/j.celrep.2022.110615","date_created":"2022-04-15T09:03:10Z","_id":"11160","status":"public","keyword":["General Biochemistry","Genetics and Molecular Biology"],"article_type":"original","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"ddc":["570"],"date_updated":"2024-03-27T23:30:44Z","file_date_updated":"2022-04-15T09:06:25Z","department":[{"_id":"JoDa"},{"_id":"GaNo"}],"pmid":1,"oa_version":"Published Version","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."}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"month":"04","intvolume":" 39","file":[{"creator":"dernst","date_updated":"2022-04-15T09:06:25Z","file_size":"7808644","date_created":"2022-04-15T09:06:25Z","file_name":"2022_CellReports_Villa.pdf","access_level":"open_access","relation":"main_file","content_type":"application/pdf","checksum":"b4e8d68f0268dec499af333e6fd5d8e1","file_id":"11164","success":1}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["2211-1247"]},"publication_status":"published","related_material":{"record":[{"status":"public","id":"12364","relation":"dissertation_contains"}]},"issue":"1","volume":39,"ec_funded":1},{"oa":1,"publisher":"Institute of Science and Technology Austria","day":"19","year":"2022","has_accepted_license":"1","date_created":"2023-01-24T13:09:57Z","doi":"10.15479/at:ista:12094","date_published":"2022-09-19T00:00:00Z","page":"152","project":[{"grant_number":"401299","name":"Probing development and reversibility of autism spectrum disorders","_id":"254BA948-B435-11E9-9278-68D0E5697425"},{"_id":"9B91375C-BA93-11EA-9121-9846C619BF3A","grant_number":"707964","name":"Critical windows and reversibility of ASD associated with mutations in chromatin remodelers"},{"call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","grant_number":"715508"},{"_id":"2690FEAC-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"I04205","name":"Identification of converging Molecular Pathways Across Chromatinopathies as Targets for Therapy"}],"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","citation":{"mla":"Dotter, Christoph. Transcriptional Consequences of Mutations in Genes Associated with Autism Spectrum Disorder. Institute of Science and Technology Austria, 2022, doi:10.15479/at:ista:12094.","ieee":"C. Dotter, “Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder,” Institute of Science and Technology Austria, 2022.","short":"C. Dotter, Transcriptional Consequences of Mutations in Genes Associated with Autism Spectrum Disorder, Institute of Science and Technology Austria, 2022.","apa":"Dotter, C. (2022). Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:12094","ama":"Dotter C. Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder. 2022. doi:10.15479/at:ista:12094","chicago":"Dotter, Christoph. “Transcriptional Consequences of Mutations in Genes Associated with Autism Spectrum Disorder.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/at:ista:12094.","ista":"Dotter C. 2022. Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder. Institute of Science and Technology Austria."},"title":"Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder","article_processing_charge":"No","author":[{"orcid":"0000-0002-9033-9096","full_name":"Dotter, Christoph","last_name":"Dotter","first_name":"Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87"}],"oa_version":"Published Version","abstract":[{"text":"Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders character\u0002ized by behavioral symptoms such as problems in social communication and interaction, as\r\nwell as repetitive, restricted behaviors and interests. These disorders show a high degree\r\nof heritability and hundreds of risk genes have been identifed using high throughput\r\nsequencing technologies. This genetic heterogeneity has hampered eforts in understanding\r\nthe pathogenesis of ASD but at the same time given rise to the concept of convergent\r\nmechanisms. Previous studies have identifed that risk genes for ASD broadly converge\r\nonto specifc functional categories with transcriptional regulation being one of the biggest\r\ngroups. In this thesis, I focus on this subgroup of genes and investigate the gene regulatory\r\nconsequences of some of them in the context of neurodevelopment.\r\nFirst, we showed that mutations in the ASD and intellectual disability risk gene Setd5 lead\r\nto perturbations of gene regulatory programs in early cell fate specifcation. In addition,\r\nadult animals display abnormal learning behavior which is mirrored at the transcriptional\r\nlevel by altered activity dependent regulation of postsynaptic gene expression. Lastly,\r\nwe link the regulatory function of Setd5 to its interaction with the Paf1 and the NCoR\r\ncomplex.\r\nSecond, by modeling the heterozygous loss of the top ASD gene CHD8 in human cerebral\r\norganoids we demonstrate profound changes in the developmental trajectories of both\r\ninhibitory and excitatory neurons using single cell RNA-sequencing. While the former\r\nwere generated earlier in CHD8+/- organoids, the generation of the latter was shifted to\r\nlater times in favor of a prolonged progenitor expansion phase and ultimately increased\r\norganoid size.\r\nFinally, by modeling heterozygous mutations for four ASD associated chromatin modifers,\r\nASH1L, KDM6B, KMT5B, and SETD5 in human cortical spheroids we show evidence of\r\nregulatory convergence across three of those genes. We observe a shift from dorsal cortical\r\nexcitatory neuron fates towards partially ventralized cell types resembling cells from the\r\nlateral ganglionic eminence. As this project is still ongoing at the time of writing, future\r\nexperiments will aim at elucidating the regulatory mechanisms underlying this shift with\r\nthe aim of linking these three ASD risk genes through biological convergence.","lang":"eng"}],"month":"09","alternative_title":["ISTA Thesis"],"language":[{"iso":"eng"}],"file":[{"embargo":"2023-09-19","file_id":"12365","checksum":"896f4cac9adb6d3f26a6605772f4e1a3","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"220923_Thesis_CDotter_Final.pdf","date_created":"2023-01-24T13:15:45Z","creator":"cchlebak","file_size":20457465,"date_updated":"2023-09-20T22:30:03Z"},{"file_id":"12482","checksum":"ad01bb20da163be6893b7af832e58419","access_level":"closed","relation":"source_file","content_type":"application/x-zip-compressed","embargo_to":"open_access","date_created":"2023-02-02T09:15:35Z","file_name":"latex_source_CDotter_Thesis_2022.zip","creator":"cchlebak","date_updated":"2023-09-20T22:30:03Z","file_size":22433512}],"degree_awarded":"PhD","publication_status":"published","publication_identifier":{"issn":["2663-337X"]},"ec_funded":1,"related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"3"},{"id":"11160","status":"public","relation":"part_of_dissertation"}]},"_id":"12364","status":"public","type":"dissertation","ddc":["570"],"date_updated":"2023-11-16T13:10:22Z","supervisor":[{"orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia"}],"department":[{"_id":"GradSch"},{"_id":"GaNo"}],"file_date_updated":"2023-09-20T22:30:03Z"},{"ec_funded":1,"issue":"11","volume":12,"publication_status":"published","publication_identifier":{"eissn":["2073-4425"]},"language":[{"iso":"eng"}],"file":[{"content_type":"application/pdf","relation":"main_file","access_level":"open_access","success":1,"checksum":"256cb832a9c3051c7dc741f6423b8cbd","file_id":"11380","file_size":1335308,"date_updated":"2022-05-16T07:02:27Z","creator":"dernst","file_name":"2021_Genes_Vasic.pdf","date_created":"2022-05-16T07:02:27Z"}],"scopus_import":"1","alternative_title":["Special Issue \"From Genes to Therapy in Autism Spectrum Disorder\""],"intvolume":" 12","month":"10","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"}],"oa_version":"Published Version","file_date_updated":"2022-05-16T07:02:27Z","department":[{"_id":"GaNo"}],"date_updated":"2023-08-14T11:46:12Z","ddc":["570"],"tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","type":"journal_article","status":"public","_id":"10281","date_created":"2021-11-14T23:01:24Z","doi":"10.3390/genes12111746","date_published":"2021-10-30T00:00:00Z","year":"2021","has_accepted_license":"1","isi":1,"publication":"Genes","day":"30","oa":1,"quality_controlled":"1","publisher":"MDPI","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.","article_processing_charge":"No","external_id":{"isi":["000834044200002"]},"author":[{"last_name":"Vasic","full_name":"Vasic, Verica","first_name":"Verica"},{"first_name":"Mattson S.O.","last_name":"Jones","full_name":"Jones, Mattson S.O."},{"full_name":"Haslinger, Denise","last_name":"Haslinger","first_name":"Denise","id":"76922BDA-3D3B-11EA-90BD-A44F3DDC885E"},{"last_name":"Knaus","full_name":"Knaus, Lisa","first_name":"Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Schmeisser, Michael J.","last_name":"Schmeisser","first_name":"Michael J."},{"last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia"},{"first_name":"Andreas G.","full_name":"Chiocchetti, Andreas G.","last_name":"Chiocchetti"}],"title":"Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment","citation":{"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).","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.","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","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","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.","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."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","project":[{"grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"grant_number":"W1232-B24","name":"Molecular Drug Targets","call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425"}],"article_number":"1746"},{"quality_controlled":"1","publisher":"eLife Sciences Publications","oa":1,"acknowledgement":"We thank Stuart Lipton and Nobuki Nakanishi for providing the Grin3a knockout mice, Beverly Davidson for the AAV-caRheb, Jose Esteban for help with behavioral and biochemical experiments, and Noelia Campillo, Rebeca Martínez-Turrillas, and Ana Navarro for expert technical help. Work was funded by the UTE project CIMA; fellowships from the Fundación Tatiana Pérez de Guzmán el Bueno, FEBS, and IBRO (to M.J.C.D.), Generalitat Valenciana (to O.E.-Z.), Juan de la Cierva (to L.G.R.), FPI-MINECO (to E.R.V., to S.N.) and Intertalentum postdoctoral program (to V.B.); ANR (GluBrain3A) and ERC Advanced Grants (#693021) (to P.P.); Ramón y Cajal program RYC2014-15784, RETOS-MINECO SAF2016-76565-R, ERANET-Neuron JTC 2019 ISCIII AC19/00077 FEDER funds (to R.A.); RETOS-MINECO SAF2017-87928-R (to A.B.); an NIH grant (NS76637) and UTHSC College of Medicine funds (to S.J.T.); and NARSAD Independent Investigator Award and grants from the MINECO (CSD2008-00005, SAF2013-48983R, SAF2016-80895-R), Generalitat Valenciana (PROMETEO 2019/020)(to I.P.O.) and Severo-Ochoa Excellence Awards (SEV-2013-0317, SEV-2017-0723).","doi":"10.7554/elife.71575","date_published":"2021-11-17T00:00:00Z","date_created":"2021-11-18T06:59:45Z","day":"17","publication":"eLife","isi":1,"has_accepted_license":"1","year":"2021","article_number":"e71575","title":"Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly","author":[{"first_name":"María J","last_name":"Conde-Dusman","full_name":"Conde-Dusman, María J"},{"full_name":"Dey, Partha N","last_name":"Dey","first_name":"Partha N"},{"full_name":"Elía-Zudaire, Óscar","last_name":"Elía-Zudaire","first_name":"Óscar"},{"first_name":"Luis E","id":"33D1B084-F248-11E8-B48F-1D18A9856A87","last_name":"Garcia Rabaneda","full_name":"Garcia Rabaneda, Luis E"},{"full_name":"García-Lira, Carmen","last_name":"García-Lira","first_name":"Carmen"},{"first_name":"Teddy","full_name":"Grand, Teddy","last_name":"Grand"},{"first_name":"Victor","last_name":"Briz","full_name":"Briz, Victor"},{"last_name":"Velasco","full_name":"Velasco, Eric R","first_name":"Eric R"},{"full_name":"Andero Galí, Raül","last_name":"Andero Galí","first_name":"Raül"},{"first_name":"Sergio","last_name":"Niñerola","full_name":"Niñerola, Sergio"},{"last_name":"Barco","full_name":"Barco, Angel","first_name":"Angel"},{"full_name":"Paoletti, Pierre","last_name":"Paoletti","first_name":"Pierre"},{"full_name":"Wesseling, John F","last_name":"Wesseling","first_name":"John F"},{"first_name":"Fabrizio","full_name":"Gardoni, Fabrizio","last_name":"Gardoni"},{"last_name":"Tavalin","full_name":"Tavalin, Steven J","first_name":"Steven J"},{"first_name":"Isabel","last_name":"Perez-Otaño","full_name":"Perez-Otaño, Isabel"}],"external_id":{"isi":["000720945900001"]},"article_processing_charge":"No","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"chicago":"Conde-Dusman, María J, Partha N Dey, Óscar Elía-Zudaire, Luis E Garcia Rabaneda, Carmen García-Lira, Teddy Grand, Victor Briz, et al. “Control of Protein Synthesis and Memory by GluN3A-NMDA Receptors through Inhibition of GIT1/MTORC1 Assembly.” ELife. eLife Sciences Publications, 2021. https://doi.org/10.7554/elife.71575.","ista":"Conde-Dusman MJ, Dey PN, Elía-Zudaire Ó, Garcia Rabaneda LE, García-Lira C, Grand T, Briz V, Velasco ER, Andero Galí R, Niñerola S, Barco A, Paoletti P, Wesseling JF, Gardoni F, Tavalin SJ, Perez-Otaño I. 2021. Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly. eLife. 10, e71575.","mla":"Conde-Dusman, María J., et al. “Control of Protein Synthesis and Memory by GluN3A-NMDA Receptors through Inhibition of GIT1/MTORC1 Assembly.” ELife, vol. 10, e71575, eLife Sciences Publications, 2021, doi:10.7554/elife.71575.","ama":"Conde-Dusman MJ, Dey PN, Elía-Zudaire Ó, et al. Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly. eLife. 2021;10. doi:10.7554/elife.71575","apa":"Conde-Dusman, M. J., Dey, P. N., Elía-Zudaire, Ó., Garcia Rabaneda, L. E., García-Lira, C., Grand, T., … Perez-Otaño, I. (2021). Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.71575","short":"M.J. Conde-Dusman, P.N. Dey, Ó. Elía-Zudaire, L.E. Garcia Rabaneda, C. García-Lira, T. Grand, V. Briz, E.R. Velasco, R. Andero Galí, S. Niñerola, A. Barco, P. Paoletti, J.F. Wesseling, F. Gardoni, S.J. Tavalin, I. Perez-Otaño, ELife 10 (2021).","ieee":"M. J. Conde-Dusman et al., “Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly,” eLife, vol. 10. eLife Sciences Publications, 2021."},"month":"11","intvolume":" 10","oa_version":"Published Version","abstract":[{"lang":"eng","text":"De novo protein synthesis is required for synapse modifications underlying stable memory encoding. Yet neurons are highly compartmentalized cells and how protein synthesis can be regulated at the synapse level is unknown. Here, we characterize neuronal signaling complexes formed by the postsynaptic scaffold GIT1, the mechanistic target of rapamycin (mTOR) kinase, and Raptor that couple synaptic stimuli to mTOR-dependent protein synthesis; and identify NMDA receptors containing GluN3A subunits as key negative regulators of GIT1 binding to mTOR. Disruption of GIT1/mTOR complexes by enhancing GluN3A expression or silencing GIT1 inhibits synaptic mTOR activation and restricts the mTOR-dependent translation of specific activity-regulated mRNAs. Conversely, GluN3A removal enables complex formation, potentiates mTOR-dependent protein synthesis, and facilitates the consolidation of associative and spatial memories in mice. The memory enhancement becomes evident with light or spaced training, can be achieved by selectively deleting GluN3A from excitatory neurons during adulthood, and does not compromise other aspects of cognition such as memory flexibility or extinction. Our findings provide mechanistic insight into synaptic translational control and reveal a potentially selective target for cognitive enhancement."}],"volume":10,"file":[{"success":1,"checksum":"59318e9e41507cec83c2f4070e6ad540","file_id":"10302","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"elife-71575-v1.pdf","date_created":"2021-11-18T07:02:02Z","creator":"lgarciar","file_size":2477302,"date_updated":"2021-11-18T07:02:02Z"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["2050-084X"]},"publication_status":"published","status":"public","keyword":["general immunology and microbiology","general biochemistry","genetics and molecular biology","general medicine","general neuroscience"],"article_type":"original","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"_id":"10301","file_date_updated":"2021-11-18T07:02:02Z","department":[{"_id":"GaNo"}],"ddc":["570"],"date_updated":"2023-08-14T11:50:50Z"},{"volume":97,"publication_identifier":{"issn":["0889-1591"]},"publication_status":"published","language":[{"iso":"eng"}],"scopus_import":"1","main_file_link":[{"url":"https://www.zora.uzh.ch/id/eprint/208855/1/ZORA208855.pdf","open_access":"1"}],"month":"10","intvolume":" 97","abstract":[{"lang":"eng","text":"Chronic psychological stress is one of the most important triggers and environmental risk factors for neuropsychiatric disorders. Chronic stress can influence all organs via the secretion of stress hormones, including glucocorticoids by the adrenal glands, which coordinate the stress response across the body. In the brain, glucocorticoid receptors (GR) are expressed by various cell types including microglia, which are its resident immune cells regulating stress-induced inflammatory processes. To study the roles of microglial GR under normal homeostatic conditions and following chronic stress, we generated a mouse model in which the GR gene is depleted in microglia specifically at adulthood to prevent developmental confounds. We first confirmed that microglia were depleted in GR in our model in males and females among the cingulate cortex and the hippocampus, both stress-sensitive brain regions. Then, cohorts of microglial-GR depleted and wild-type (WT) adult female mice were housed for 3 weeks in a standard or stressful condition, using a chronic unpredictable mild stress (CUMS) paradigm. CUMS induced stress-related behavior in both microglial-GR depleted and WT animals as demonstrated by a decrease of both saccharine preference and progressive ratio breakpoint. Nevertheless, the hippocampal microglial and neural mechanisms underlying the adaptation to stress occurred differently between the two genotypes. Upon CUMS exposure, microglial morphology was altered in the WT controls, without any apparent effect in microglial-GR depleted mice. Furthermore, in the standard environment condition, GR depleted-microglia showed increased expression of pro-inflammatory genes, and genes involved in microglial homeostatic functions (such as Trem2, Cx3cr1 and Mertk). On the contrary, in CUMS condition, GR depleted-microglia showed reduced expression levels of pro-inflammatory genes and increased neuroprotective as well as anti-inflammatory genes compared to WT-microglia. Moreover, in microglial-GR depleted mice, but not in WT mice, CUMS led to a significant reduction of CA1 long-term potentiation and paired-pulse ratio. Lastly, differences in adult hippocampal neurogenesis were observed between the genotypes during normal homeostatic conditions, with microglial-GR deficiency increasing the formation of newborn neurons in the dentate gyrus subgranular zone independently from stress exposure. Together, these findings indicate that, although the deletion of microglial GR did not prevent the animal’s ability to respond to stress, it contributed to modulating hippocampal functions in both standard and stressful conditions, notably by shaping the microglial response to chronic stress."}],"pmid":1,"oa_version":"Submitted Version","department":[{"_id":"GaNo"}],"date_updated":"2023-10-03T09:49:18Z","type":"journal_article","article_type":"original","status":"public","_id":"9953","page":"423-439","doi":"10.1016/j.bbi.2021.07.022","date_published":"2021-10-01T00:00:00Z","date_created":"2021-08-22T22:01:21Z","isi":1,"year":"2021","day":"01","publication":"Brain, Behavior, and Immunity","publisher":"Elsevier","quality_controlled":"1","oa":1,"acknowledgement":"We acknowledge that Université Laval stands on the traditional and unceded land of the Huron-Wendat peoples; and that the University of Victoria exists on the territory of the Lekwungen peoples and that the Songhees, Esquimalt and WSÁNEÆ peoples have relationships to this land. We thank Emmanuel Planel for the access to the epifluorescence microscope and Julie-Christine Lévesque at the Bioimaging Platform of CRCHU de Québec-Université Laval for technical assistance. We also thank the Centre for Advanced Materials and Related Technology for the access to the confocal microscope with Airyscan. K.P. was supported by a doctoral scholarship from Fonds de Recherche du Québec – Santé (FRQS), an excellence award from Fondation du CHU de Québec, as well as from Centre Thématique de Recherche en Neurosciences and from Fondation Famille-Choquette. K.B. was supported by excellence scholarships from Université Laval and Fondation du CHU de Québec. S.G. is supported by FIRC-AIRC fellowship for Italy 22329/2018 and by Pilot ARISLA NKINALS 2019. C.W.H. and J.C.S. were supported by postdoctoral fellowships from FRQS. This study was funded by a Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery grant (RGPIN-2014-05308) awarded to M.E.T., by ERANET neuron 2017 MicroSynDep to M.E.T. and I.B., and by the Italian Ministry of Health, grant RF-2018-12367249 to I.B, by PRIN 2017, AIRC 2019 and Ministero della Salute RF2018 to C.L. M.E.T. is a Tier II Canada Research Chair in Neurobiology of Aging and Cognition.","author":[{"first_name":"Katherine","last_name":"Picard","full_name":"Picard, Katherine"},{"last_name":"Bisht","full_name":"Bisht, Kanchan","first_name":"Kanchan"},{"full_name":"Poggini, Silvia","last_name":"Poggini","first_name":"Silvia"},{"first_name":"Stefano","last_name":"Garofalo","full_name":"Garofalo, Stefano"},{"full_name":"Golia, Maria Teresa","last_name":"Golia","first_name":"Maria Teresa"},{"full_name":"Basilico, Bernadette","orcid":"0000-0003-1843-3173","last_name":"Basilico","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","first_name":"Bernadette"},{"first_name":"Fatima","full_name":"Abdallah, Fatima","last_name":"Abdallah"},{"first_name":"Naomi","last_name":"Ciano Albanese","full_name":"Ciano Albanese, Naomi"},{"first_name":"Irmgard","full_name":"Amrein, Irmgard","last_name":"Amrein"},{"first_name":"Nathalie","full_name":"Vernoux, Nathalie","last_name":"Vernoux"},{"full_name":"Sharma, Kaushik","last_name":"Sharma","first_name":"Kaushik"},{"first_name":"Chin Wai","full_name":"Hui, Chin Wai","last_name":"Hui"},{"first_name":"Julie","full_name":"C. Savage, Julie","last_name":"C. Savage"},{"first_name":"Cristina","last_name":"Limatola","full_name":"Limatola, Cristina"},{"first_name":"Davide","full_name":"Ragozzino, Davide","last_name":"Ragozzino"},{"first_name":"Laura","last_name":"Maggi","full_name":"Maggi, Laura"},{"first_name":"Igor","full_name":"Branchi, Igor","last_name":"Branchi"},{"first_name":"Marie Ève","last_name":"Tremblay","full_name":"Tremblay, Marie Ève"}],"article_processing_charge":"No","external_id":{"isi":["000702878400007"],"pmid":["34343616"]},"title":"Microglial-glucocorticoid receptor depletion alters the response of hippocampal microglia and neurons in a chronic unpredictable mild stress paradigm in female mice","citation":{"chicago":"Picard, Katherine, Kanchan Bisht, Silvia Poggini, Stefano Garofalo, Maria Teresa Golia, Bernadette Basilico, Fatima Abdallah, et al. “Microglial-Glucocorticoid Receptor Depletion Alters the Response of Hippocampal Microglia and Neurons in a Chronic Unpredictable Mild Stress Paradigm in Female Mice.” Brain, Behavior, and Immunity. Elsevier, 2021. https://doi.org/10.1016/j.bbi.2021.07.022.","ista":"Picard K, Bisht K, Poggini S, Garofalo S, Golia MT, Basilico B, Abdallah F, Ciano Albanese N, Amrein I, Vernoux N, Sharma K, Hui CW, C. Savage J, Limatola C, Ragozzino D, Maggi L, Branchi I, Tremblay MÈ. 2021. Microglial-glucocorticoid receptor depletion alters the response of hippocampal microglia and neurons in a chronic unpredictable mild stress paradigm in female mice. Brain, Behavior, and Immunity. 97, 423–439.","mla":"Picard, Katherine, et al. “Microglial-Glucocorticoid Receptor Depletion Alters the Response of Hippocampal Microglia and Neurons in a Chronic Unpredictable Mild Stress Paradigm in Female Mice.” Brain, Behavior, and Immunity, vol. 97, Elsevier, 2021, pp. 423–39, doi:10.1016/j.bbi.2021.07.022.","ama":"Picard K, Bisht K, Poggini S, et al. Microglial-glucocorticoid receptor depletion alters the response of hippocampal microglia and neurons in a chronic unpredictable mild stress paradigm in female mice. Brain, Behavior, and Immunity. 2021;97:423-439. doi:10.1016/j.bbi.2021.07.022","apa":"Picard, K., Bisht, K., Poggini, S., Garofalo, S., Golia, M. T., Basilico, B., … Tremblay, M. È. (2021). Microglial-glucocorticoid receptor depletion alters the response of hippocampal microglia and neurons in a chronic unpredictable mild stress paradigm in female mice. Brain, Behavior, and Immunity. Elsevier. https://doi.org/10.1016/j.bbi.2021.07.022","short":"K. Picard, K. Bisht, S. Poggini, S. Garofalo, M.T. Golia, B. Basilico, F. Abdallah, N. Ciano Albanese, I. Amrein, N. Vernoux, K. Sharma, C.W. Hui, J. C. Savage, C. Limatola, D. Ragozzino, L. Maggi, I. Branchi, M.È. Tremblay, Brain, Behavior, and Immunity 97 (2021) 423–439.","ieee":"K. Picard et al., “Microglial-glucocorticoid receptor depletion alters the response of hippocampal microglia and neurons in a chronic unpredictable mild stress paradigm in female mice,” Brain, Behavior, and Immunity, vol. 97. Elsevier, pp. 423–439, 2021."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87"},{"department":[{"_id":"GaNo"}],"date_updated":"2023-10-18T06:45:30Z","article_type":"original","type":"journal_article","status":"public","_id":"8730","volume":41,"issue":"7","publication_status":"published","publication_identifier":{"eissn":["1559-7016"],"issn":["0271-678x"]},"language":[{"iso":"eng"}],"main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221757/","open_access":"1"}],"scopus_import":"1","intvolume":" 41","month":"07","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"}],"oa_version":"Published Version","pmid":1,"article_processing_charge":"No","external_id":{"isi":["000664214100012"],"pmid":["33081568"]},"author":[{"last_name":"Tournier","full_name":"Tournier, N","first_name":"N"},{"first_name":"S","full_name":"Goutal, S","last_name":"Goutal"},{"first_name":"S","last_name":"Mairinger","full_name":"Mairinger, S"},{"last_name":"Lozano","full_name":"Lozano, IH","first_name":"IH"},{"full_name":"Filip, T","last_name":"Filip","first_name":"T"},{"first_name":"M","full_name":"Sauberer, M","last_name":"Sauberer"},{"first_name":"F","full_name":"Caillé, F","last_name":"Caillé"},{"first_name":"L","last_name":"Breuil","full_name":"Breuil, L"},{"first_name":"J","full_name":"Stanek, J","last_name":"Stanek"},{"first_name":"AF","last_name":"Freeman","full_name":"Freeman, AF"},{"last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Truillet","full_name":"Truillet, C","first_name":"C"},{"full_name":"Wanek, T","last_name":"Wanek","first_name":"T"},{"last_name":"Langer","full_name":"Langer, O","first_name":"O"}],"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","citation":{"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.","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.","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.","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","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","short":"N. Tournier, S. Goutal, S. Mairinger, I. Lozano, T. Filip, M. Sauberer, F. Caillé, L. Breuil, J. Stanek, A. Freeman, G. Novarino, C. Truillet, T. Wanek, O. Langer, Journal of Cerebral Blood Flow and Metabolism 41 (2021) 1634–1646.","ieee":"N. Tournier 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."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","page":"1634-1646","date_created":"2020-11-06T08:39:01Z","doi":"10.1177/0271678X20965500","date_published":"2021-07-01T00:00:00Z","year":"2021","isi":1,"publication":"Journal of Cerebral Blood Flow and Metabolism","day":"01","oa":1,"quality_controlled":"1","publisher":"SAGE Publications"},{"project":[{"_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411"},{"grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Molecular Drug Targets","grant_number":"W1232-B24"},{"name":"Neural stem cells in autism and epilepsy","grant_number":"F07807","_id":"05A0D778-7A3F-11EA-A408-12923DDC885E"},{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"I03600","name":"Optical control of synaptic function via adhesion molecules"}],"article_number":"3058","title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","article_processing_charge":"No","external_id":{"isi":["000658769900010"]},"author":[{"last_name":"Morandell","full_name":"Morandell, Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","first_name":"Jasmin"},{"first_name":"Lena A","id":"29A8453C-F248-11E8-B48F-1D18A9856A87","last_name":"Schwarz","full_name":"Schwarz, Lena A"},{"first_name":"Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","last_name":"Basilico","orcid":"0000-0003-1843-3173","full_name":"Basilico, Bernadette"},{"id":"4323B49C-F248-11E8-B48F-1D18A9856A87","first_name":"Saren","last_name":"Tasciyan","full_name":"Tasciyan, Saren","orcid":"0000-0003-1671-393X"},{"first_name":"Georgi A","id":"38C393BE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8370-6161","full_name":"Dimchev, Georgi A","last_name":"Dimchev"},{"last_name":"Nicolas","full_name":"Nicolas, Armel","first_name":"Armel","id":"2A103192-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Sommer","full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Kreuzinger, Caroline","last_name":"Kreuzinger","first_name":"Caroline","id":"382077BA-F248-11E8-B48F-1D18A9856A87"},{"id":"4C66542E-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph","orcid":"0000-0002-9033-9096","full_name":"Dotter, Christoph","last_name":"Dotter"},{"full_name":"Knaus, Lisa","last_name":"Knaus","first_name":"Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Dobler","full_name":"Dobler, Zoe","id":"D23090A2-9057-11EA-883A-A8396FC7A38F","first_name":"Zoe"},{"first_name":"Emanuele","last_name":"Cacci","full_name":"Cacci, Emanuele"},{"first_name":"Florian KM","id":"48AD8942-F248-11E8-B48F-1D18A9856A87","last_name":"Schur","orcid":"0000-0003-4790-8078","full_name":"Schur, Florian KM"},{"first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","last_name":"Danzl","full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973"},{"first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"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.","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","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","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.","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.","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."},"oa":1,"quality_controlled":"1","publisher":"Springer Nature","acknowledgement":"We thank A. Coll Manzano, F. Freeman, M. Ladron de Guevara, and A. Ç. Yahya for technical assistance, S. Deixler, A. Lepold, and A. Schlerka for the management of our animal colony, as well as M. Schunn and the Preclinical Facility team for technical assistance. We thank K. Heesom and her team at the University of Bristol Proteomics Facility for the proteomics sample preparation, data generation, and analysis support. We thank Y. B. Simon for kindly providing the plasmid for lentiviral labeling. Further, we thank M. Sixt for his advice regarding cell migration and the fruitful discussions. This work was supported by the ISTPlus postdoctoral fellowship (Grant Agreement No. 754411) to B.B., by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 (REVERSEAUTISM), and by the Austrian Science Fund (FWF) to G.N. (DK W1232-B24 and SFB F7807-B) and to J.G.D (I3600-B27).","date_created":"2021-05-28T11:49:46Z","doi":"10.1038/s41467-021-23123-x","date_published":"2021-05-24T00:00:00Z","publication":"Nature Communications","day":"24","year":"2021","has_accepted_license":"1","isi":1,"keyword":["General Biochemistry","Genetics and Molecular Biology"],"status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"article_type":"original","type":"journal_article","_id":"9429","department":[{"_id":"GaNo"},{"_id":"JoDa"},{"_id":"FlSc"},{"_id":"MiSi"},{"_id":"LifeSc"},{"_id":"Bio"}],"file_date_updated":"2021-05-28T12:39:43Z","ddc":["572"],"date_updated":"2024-03-27T23:30:23Z","intvolume":" 12","month":"05","oa_version":"Published Version","acknowledged_ssus":[{"_id":"PreCl"}],"abstract":[{"lang":"eng","text":"De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 lead to autism spectrum disorder (ASD). In mouse, constitutive haploinsufficiency leads to motor coordination deficits as well as ASD-relevant social and cognitive impairments. However, induction of Cul3 haploinsufficiency later in life does not lead to ASD-relevant behaviors, pointing to an important role of Cul3 during a critical developmental window. Here we show that Cul3 is essential to regulate neuronal migration and, therefore, constitutive Cul3 heterozygous mutant mice display cortical lamination abnormalities. At the molecular level, we found that Cul3 controls neuronal migration by tightly regulating the amount of Plastin3 (Pls3), a previously unrecognized player of neural migration. Furthermore, we found that Pls3 cell-autonomously regulates cell migration by regulating actin cytoskeleton organization, and its levels are inversely proportional to neural migration speed. Finally, we provide evidence that cellular phenotypes associated with autism-linked gene haploinsufficiency can be rescued by transcriptional activation of the intact allele in vitro, offering a proof of concept for a potential therapeutic approach for ASDs."}],"ec_funded":1,"related_material":{"record":[{"relation":"earlier_version","id":"7800","status":"public"},{"relation":"dissertation_contains","id":"12401","status":"public"}],"link":[{"url":"https://ist.ac.at/en/news/defective-gene-slows-down-brain-cells/","relation":"press_release"}]},"volume":12,"issue":"1","language":[{"iso":"eng"}],"file":[{"date_updated":"2021-05-28T12:39:43Z","file_size":9358599,"creator":"kschuh","date_created":"2021-05-28T12:39:43Z","file_name":"2021_NatureCommunications_Morandell.pdf","content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"337e0f7959c35ec959984cacdcb472ba","file_id":"9430","success":1}],"publication_status":"published","publication_identifier":{"eissn":["2041-1723"]}},{"quality_controlled":"1","publisher":"Wiley","acknowledgement":" Dipartimento DiSS, Università degli Studi di Milano, Grant/Award Number: Linea 2; Fondazione Cariplo, Grant/Award Number: 2015-0783; German Federal Ministry of Education and Research (BMBF), Grant/Award Number: CHROMATIN-Net; Medical Faculty of the University of Lübeck, Grant/Award Number: J09-2017; Nickel & Co S.p.A.; Università degli Studi di Milano, Grant/Award Numbers: Molecular & Translational Medicine PhD Scholarship, Translational Medicine PhD Scholarship","date_published":"2020-01-01T00:00:00Z","doi":"10.1111/cge.13674","date_created":"2019-12-04T16:10:59Z","page":"3-11","day":"01","publication":"Clinical Genetics","isi":1,"year":"2020","title":"Chromatinopathies: A focus on Cornelia de Lange syndrome","author":[{"last_name":"Avagliano","full_name":"Avagliano, Laura","first_name":"Laura"},{"last_name":"Parenti","full_name":"Parenti, Ilaria","id":"D93538B0-5B71-11E9-AC62-02EBE5697425","first_name":"Ilaria"},{"first_name":"Paolo","last_name":"Grazioli","full_name":"Grazioli, Paolo"},{"first_name":"Elisabetta","last_name":"Di Fede","full_name":"Di Fede, Elisabetta"},{"first_name":"Chiara","last_name":"Parodi","full_name":"Parodi, Chiara"},{"first_name":"Milena","last_name":"Mariani","full_name":"Mariani, Milena"},{"last_name":"Kaiser","full_name":"Kaiser, Frank J.","first_name":"Frank J."},{"full_name":"Selicorni, Angelo","last_name":"Selicorni","first_name":"Angelo"},{"full_name":"Gervasini, Cristina","last_name":"Gervasini","first_name":"Cristina"},{"last_name":"Massa","full_name":"Massa, Valentina","first_name":"Valentina"}],"article_processing_charge":"No","external_id":{"pmid":["31721174"],"isi":["000562561800001"]},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"ista":"Avagliano L, Parenti I, Grazioli P, Di Fede E, Parodi C, Mariani M, Kaiser FJ, Selicorni A, Gervasini C, Massa V. 2020. Chromatinopathies: A focus on Cornelia de Lange syndrome. Clinical Genetics. 97(1), 3–11.","chicago":"Avagliano, Laura, Ilaria Parenti, Paolo Grazioli, Elisabetta Di Fede, Chiara Parodi, Milena Mariani, Frank J. Kaiser, Angelo Selicorni, Cristina Gervasini, and Valentina Massa. “Chromatinopathies: A Focus on Cornelia de Lange Syndrome.” Clinical Genetics. Wiley, 2020. https://doi.org/10.1111/cge.13674.","ama":"Avagliano L, Parenti I, Grazioli P, et al. Chromatinopathies: A focus on Cornelia de Lange syndrome. Clinical Genetics. 2020;97(1):3-11. doi:10.1111/cge.13674","apa":"Avagliano, L., Parenti, I., Grazioli, P., Di Fede, E., Parodi, C., Mariani, M., … Massa, V. (2020). Chromatinopathies: A focus on Cornelia de Lange syndrome. Clinical Genetics. Wiley. https://doi.org/10.1111/cge.13674","short":"L. Avagliano, I. Parenti, P. Grazioli, E. Di Fede, C. Parodi, M. Mariani, F.J. Kaiser, A. Selicorni, C. Gervasini, V. Massa, Clinical Genetics 97 (2020) 3–11.","ieee":"L. Avagliano et al., “Chromatinopathies: A focus on Cornelia de Lange syndrome,” Clinical Genetics, vol. 97, no. 1. Wiley, pp. 3–11, 2020.","mla":"Avagliano, Laura, et al. “Chromatinopathies: A Focus on Cornelia de Lange Syndrome.” Clinical Genetics, vol. 97, no. 1, Wiley, 2020, pp. 3–11, doi:10.1111/cge.13674."},"month":"01","intvolume":" 97","scopus_import":"1","pmid":1,"oa_version":"None","abstract":[{"lang":"eng","text":"In recent years, many genes have been associated with chromatinopathies classified as “Cornelia de Lange Syndrome‐like.” It is known that the phenotype of these patients becomes less recognizable, overlapping to features characteristic of other syndromes caused by genetic variants affecting different regulators of chromatin structure and function. Therefore, Cornelia de Lange syndrome diagnosis might be arduous due to the seldom discordance between unexpected molecular diagnosis and clinical evaluation. Here, we review the molecular features of Cornelia de Lange syndrome, supporting the hypothesis that “CdLS‐like syndromes” are part of a larger “rare disease family” sharing multiple clinical features and common disrupted molecular pathways."}],"volume":97,"issue":"1","language":[{"iso":"eng"}],"publication_identifier":{"issn":["0009-9163"],"eissn":["1399-0004"]},"publication_status":"published","status":"public","article_type":"review","type":"journal_article","_id":"7149","department":[{"_id":"GaNo"}],"date_updated":"2023-08-17T14:06:20Z"},{"publisher":"MDPI","quality_controlled":"1","oa":1,"has_accepted_license":"1","isi":1,"year":"2020","day":"04","publication":"International Journal of Molecular Sciences","doi":"10.3390/ijms21031042","date_published":"2020-02-04T00:00:00Z","date_created":"2020-02-16T23:00:49Z","article_number":"1042","citation":{"short":"A. Latorre-Pellicer, Á. Ascaso, L. Trujillano, M. Gil-Salvador, M. Arnedo, C. Lucia-Campos, R. Antoñanzas-Pérez, I. Marcos-Alcalde, I. Parenti, G. Bueno-Lozano, A. Musio, B. Puisac, F.J. Kaiser, F.J. Ramos, P. Gómez-Puertas, J. Pié, International Journal of Molecular Sciences 21 (2020).","ieee":"A. Latorre-Pellicer et al., “Evaluating Face2Gene as a tool to identify Cornelia de Lange syndrome by facial phenotypes,” International Journal of Molecular Sciences, vol. 21, no. 3. MDPI, 2020.","apa":"Latorre-Pellicer, A., Ascaso, Á., Trujillano, L., Gil-Salvador, M., Arnedo, M., Lucia-Campos, C., … Pié, J. (2020). Evaluating Face2Gene as a tool to identify Cornelia de Lange syndrome by facial phenotypes. International Journal of Molecular Sciences. MDPI. https://doi.org/10.3390/ijms21031042","ama":"Latorre-Pellicer A, Ascaso Á, Trujillano L, et al. Evaluating Face2Gene as a tool to identify Cornelia de Lange syndrome by facial phenotypes. International Journal of Molecular Sciences. 2020;21(3). doi:10.3390/ijms21031042","mla":"Latorre-Pellicer, Ana, et al. “Evaluating Face2Gene as a Tool to Identify Cornelia de Lange Syndrome by Facial Phenotypes.” International Journal of Molecular Sciences, vol. 21, no. 3, 1042, MDPI, 2020, doi:10.3390/ijms21031042.","ista":"Latorre-Pellicer A, Ascaso Á, Trujillano L, Gil-Salvador M, Arnedo M, Lucia-Campos C, Antoñanzas-Pérez R, Marcos-Alcalde I, Parenti I, Bueno-Lozano G, Musio A, Puisac B, Kaiser FJ, Ramos FJ, Gómez-Puertas P, Pié J. 2020. Evaluating Face2Gene as a tool to identify Cornelia de Lange syndrome by facial phenotypes. International Journal of Molecular Sciences. 21(3), 1042.","chicago":"Latorre-Pellicer, Ana, Ángela Ascaso, Laura Trujillano, Marta Gil-Salvador, Maria Arnedo, Cristina Lucia-Campos, Rebeca Antoñanzas-Pérez, et al. “Evaluating Face2Gene as a Tool to Identify Cornelia de Lange Syndrome by Facial Phenotypes.” International Journal of Molecular Sciences. MDPI, 2020. https://doi.org/10.3390/ijms21031042."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","author":[{"first_name":"Ana","full_name":"Latorre-Pellicer, Ana","last_name":"Latorre-Pellicer"},{"last_name":"Ascaso","full_name":"Ascaso, Ángela","first_name":"Ángela"},{"full_name":"Trujillano, Laura","last_name":"Trujillano","first_name":"Laura"},{"full_name":"Gil-Salvador, Marta","last_name":"Gil-Salvador","first_name":"Marta"},{"first_name":"Maria","last_name":"Arnedo","full_name":"Arnedo, Maria"},{"first_name":"Cristina","full_name":"Lucia-Campos, Cristina","last_name":"Lucia-Campos"},{"first_name":"Rebeca","full_name":"Antoñanzas-Pérez, Rebeca","last_name":"Antoñanzas-Pérez"},{"full_name":"Marcos-Alcalde, Iñigo","last_name":"Marcos-Alcalde","first_name":"Iñigo"},{"last_name":"Parenti","full_name":"Parenti, Ilaria","first_name":"Ilaria","id":"D93538B0-5B71-11E9-AC62-02EBE5697425"},{"first_name":"Gloria","last_name":"Bueno-Lozano","full_name":"Bueno-Lozano, Gloria"},{"first_name":"Antonio","last_name":"Musio","full_name":"Musio, Antonio"},{"first_name":"Beatriz","last_name":"Puisac","full_name":"Puisac, Beatriz"},{"last_name":"Kaiser","full_name":"Kaiser, Frank J.","first_name":"Frank J."},{"first_name":"Feliciano J.","last_name":"Ramos","full_name":"Ramos, Feliciano J."},{"first_name":"Paulino","full_name":"Gómez-Puertas, Paulino","last_name":"Gómez-Puertas"},{"full_name":"Pié, Juan","last_name":"Pié","first_name":"Juan"}],"article_processing_charge":"No","external_id":{"isi":["000522551606028"]},"title":"Evaluating Face2Gene as a tool to identify Cornelia de Lange syndrome by facial phenotypes","abstract":[{"text":"Characteristic or classic phenotype of Cornelia de Lange syndrome (CdLS) is associated with a recognisable facial pattern. However, the heterogeneity in causal genes and the presence of overlapping syndromes have made it increasingly difficult to diagnose only by clinical features. DeepGestalt technology, and its app Face2Gene, is having a growing impact on the diagnosis and management of genetic diseases by analysing the features of affected individuals. Here, we performed a phenotypic study on a cohort of 49 individuals harbouring causative variants in known CdLS genes in order to evaluate Face2Gene utility and sensitivity in the clinical diagnosis of CdLS. Based on the profile images of patients, a diagnosis of CdLS was within the top five predicted syndromes for 97.9% of our cases and even listed as first prediction for 83.7%. The age of patients did not seem to affect the prediction accuracy, whereas our results indicate a correlation between the clinical score and affected genes. Furthermore, each gene presents a different pattern recognition that may be used to develop new neural networks with the goal of separating different genetic subtypes in CdLS. Overall, we conclude that computer-assisted image analysis based on deep learning could support the clinical diagnosis of CdLS.","lang":"eng"}],"oa_version":"Published Version","scopus_import":"1","month":"02","intvolume":" 21","publication_identifier":{"issn":["16616596"],"eissn":["14220067"]},"publication_status":"published","file":[{"access_level":"open_access","relation":"main_file","content_type":"application/pdf","file_id":"7496","checksum":"0e6658c4fe329d55d4d9bef01c5b15d0","creator":"dernst","date_updated":"2020-07-14T12:47:59Z","file_size":4271234,"date_created":"2020-02-18T07:49:22Z","file_name":"2020_IntMolecSciences_Latorre.pdf"}],"language":[{"iso":"eng"}],"volume":21,"issue":"3","_id":"7488","article_type":"original","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","date_updated":"2023-08-18T06:35:41Z","ddc":["570"],"department":[{"_id":"GaNo"}],"file_date_updated":"2020-07-14T12:47:59Z"},{"publisher":"EMBO Press","quality_controlled":"1","oa":1,"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.","date_published":"2020-03-02T00:00:00Z","doi":"10.15252/embj.2019103358","date_created":"2020-03-15T23:00:55Z","has_accepted_license":"1","isi":1,"year":"2020","day":"02","publication":"EMBO Journal","article_number":"e103358","author":[{"last_name":"Weinert","full_name":"Weinert, Stefanie","first_name":"Stefanie"},{"last_name":"Gimber","full_name":"Gimber, Niclas","first_name":"Niclas"},{"full_name":"Deuschel, Dorothea","last_name":"Deuschel","first_name":"Dorothea"},{"full_name":"Stuhlmann, Till","last_name":"Stuhlmann","first_name":"Till"},{"first_name":"Dmytro","last_name":"Puchkov","full_name":"Puchkov, Dmytro"},{"first_name":"Zohreh","full_name":"Farsi, Zohreh","last_name":"Farsi"},{"first_name":"Carmen F.","last_name":"Ludwig","full_name":"Ludwig, Carmen F."},{"last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia"},{"first_name":"Karen I.","full_name":"López-Cayuqueo, Karen I.","last_name":"López-Cayuqueo"},{"first_name":"Rosa","last_name":"Planells-Cases","full_name":"Planells-Cases, Rosa"},{"first_name":"Thomas J.","last_name":"Jentsch","full_name":"Jentsch, Thomas J."}],"external_id":{"isi":["000517335000001"],"pmid":["32118314"]},"article_processing_charge":"No","title":"Uncoupling endosomal CLC chloride/proton exchange causes severe neurodegeneration","citation":{"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.","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","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","short":"S. Weinert, N. Gimber, D. Deuschel, T. Stuhlmann, D. Puchkov, Z. Farsi, C.F. Ludwig, G. Novarino, K.I. López-Cayuqueo, R. Planells-Cases, T.J. Jentsch, EMBO Journal 39 (2020).","ieee":"S. Weinert et al., “Uncoupling endosomal CLC chloride/proton exchange causes severe neurodegeneration,” EMBO Journal, vol. 39. EMBO Press, 2020.","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.","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."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","scopus_import":"1","month":"03","intvolume":" 39","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"}],"pmid":1,"oa_version":"Published Version","volume":39,"publication_identifier":{"eissn":["14602075"],"issn":["02614189"]},"publication_status":"published","file":[{"relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_id":"7615","checksum":"82750a7a93e3740decbce8474004111a","creator":"dernst","file_size":12243278,"date_updated":"2020-07-14T12:48:00Z","file_name":"2020_EMBO_Weinert.pdf","date_created":"2020-03-23T13:51:11Z"}],"language":[{"iso":"eng"}],"type":"journal_article","article_type":"original","tmp":{"short":"CC BY-NC-ND (4.0)","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","image":"/images/cc_by_nc_nd.png"},"status":"public","_id":"7586","department":[{"_id":"GaNo"}],"file_date_updated":"2020-07-14T12:48:00Z","date_updated":"2023-08-18T07:07:36Z","ddc":["570"]},{"intvolume":" 31","month":"05","scopus_import":"1","oa_version":"Published Version","abstract":[{"lang":"eng","text":"The NIPBL/MAU2 heterodimer loads cohesin onto chromatin. Mutations inNIPBLaccount for most cases ofthe rare developmental disorder Cornelia de Lange syndrome (CdLS). Here we report aMAU2 variant causing CdLS, a deletion of seven amino acids that impairs the interaction between MAU2 and the NIPBL N terminus.Investigating this interaction, we discovered that MAU2 and the NIPBL N terminus are largely dispensable fornormal cohesin and NIPBL function in cells with a NIPBL early truncating mutation. Despite a predicted fataloutcome of an out-of-frame single nucleotide duplication inNIPBL, engineered in two different cell lines,alternative translation initiation yields a form of NIPBL missing N-terminal residues. This form cannot interactwith MAU2, but binds DNA and mediates cohesin loading. Altogether, our work reveals that cohesin loading can occur independently of functional NIPBL/MAU2 complexes and highlights a novel mechanism protectiveagainst out-of-frame mutations that is potentially relevant for other genetic conditions."}],"issue":"7","volume":31,"language":[{"iso":"eng"}],"file":[{"file_id":"7892","checksum":"64d8f7467731ee5c166b10b939b8310b","content_type":"application/pdf","access_level":"open_access","relation":"main_file","date_created":"2020-05-26T11:05:01Z","file_name":"2020_CellReports_Parenti.pdf","date_updated":"2020-07-14T12:48:04Z","file_size":4695682,"creator":"dernst"}],"publication_status":"published","publication_identifier":{"eissn":["22111247"]},"status":"public","tmp":{"short":"CC BY-NC-ND (4.0)","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","image":"/images/cc_by_nc_nd.png"},"article_type":"original","type":"journal_article","_id":"7877","department":[{"_id":"GaNo"}],"file_date_updated":"2020-07-14T12:48:04Z","ddc":["570"],"date_updated":"2023-08-21T06:27:47Z","oa":1,"quality_controlled":"1","publisher":"Elsevier","date_created":"2020-05-24T22:00:57Z","date_published":"2020-05-19T00:00:00Z","doi":"10.1016/j.celrep.2020.107647","publication":"Cell Reports","day":"19","year":"2020","isi":1,"has_accepted_license":"1","article_number":"107647","title":"MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader subunits and cause Cornelia de Lange syndrome","article_processing_charge":"No","external_id":{"isi":["000535655200005"]},"author":[{"full_name":"Parenti, Ilaria","last_name":"Parenti","id":"D93538B0-5B71-11E9-AC62-02EBE5697425","first_name":"Ilaria"},{"last_name":"Diab","full_name":"Diab, Farah","first_name":"Farah"},{"full_name":"Gil, Sara Ruiz","last_name":"Gil","first_name":"Sara Ruiz"},{"full_name":"Mulugeta, Eskeatnaf","last_name":"Mulugeta","first_name":"Eskeatnaf"},{"first_name":"Valentina","full_name":"Casa, Valentina","last_name":"Casa"},{"first_name":"Riccardo","full_name":"Berutti, Riccardo","last_name":"Berutti"},{"first_name":"Rutger W.W.","last_name":"Brouwer","full_name":"Brouwer, Rutger W.W."},{"first_name":"Valerie","full_name":"Dupé, Valerie","last_name":"Dupé"},{"first_name":"Juliane","last_name":"Eckhold","full_name":"Eckhold, Juliane"},{"first_name":"Elisabeth","full_name":"Graf, Elisabeth","last_name":"Graf"},{"first_name":"Beatriz","full_name":"Puisac, Beatriz","last_name":"Puisac"},{"last_name":"Ramos","full_name":"Ramos, Feliciano","first_name":"Feliciano"},{"last_name":"Schwarzmayr","full_name":"Schwarzmayr, Thomas","first_name":"Thomas"},{"first_name":"Macarena Moronta","last_name":"Gines","full_name":"Gines, Macarena Moronta"},{"first_name":"Thomas","last_name":"Van Staveren","full_name":"Van Staveren, Thomas"},{"first_name":"Wilfred F.J.","last_name":"Van Ijcken","full_name":"Van Ijcken, Wilfred F.J."},{"first_name":"Tim M.","full_name":"Strom, Tim M.","last_name":"Strom"},{"full_name":"Pié, Juan","last_name":"Pié","first_name":"Juan"},{"first_name":"Erwan","last_name":"Watrin","full_name":"Watrin, Erwan"},{"full_name":"Kaiser, Frank J.","last_name":"Kaiser","first_name":"Frank J."},{"last_name":"Wendt","full_name":"Wendt, Kerstin S.","first_name":"Kerstin S."}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"ista":"Parenti I, Diab F, Gil SR, Mulugeta E, Casa V, Berutti R, Brouwer RWW, Dupé V, Eckhold J, Graf E, Puisac B, Ramos F, Schwarzmayr T, Gines MM, Van Staveren T, Van Ijcken WFJ, Strom TM, Pié J, Watrin E, Kaiser FJ, Wendt KS. 2020. MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader subunits and cause Cornelia de Lange syndrome. Cell Reports. 31(7), 107647.","chicago":"Parenti, Ilaria, Farah Diab, Sara Ruiz Gil, Eskeatnaf Mulugeta, Valentina Casa, Riccardo Berutti, Rutger W.W. Brouwer, et al. “MAU2 and NIPBL Variants Impair the Heterodimerization of the Cohesin Loader Subunits and Cause Cornelia de Lange Syndrome.” Cell Reports. Elsevier, 2020. https://doi.org/10.1016/j.celrep.2020.107647.","ieee":"I. Parenti et al., “MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader subunits and cause Cornelia de Lange syndrome,” Cell Reports, vol. 31, no. 7. Elsevier, 2020.","short":"I. Parenti, F. Diab, S.R. Gil, E. Mulugeta, V. Casa, R. Berutti, R.W.W. Brouwer, V. Dupé, J. Eckhold, E. Graf, B. Puisac, F. Ramos, T. Schwarzmayr, M.M. Gines, T. Van Staveren, W.F.J. Van Ijcken, T.M. Strom, J. Pié, E. Watrin, F.J. Kaiser, K.S. Wendt, Cell Reports 31 (2020).","apa":"Parenti, I., Diab, F., Gil, S. R., Mulugeta, E., Casa, V., Berutti, R., … Wendt, K. S. (2020). MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader subunits and cause Cornelia de Lange syndrome. Cell Reports. Elsevier. https://doi.org/10.1016/j.celrep.2020.107647","ama":"Parenti I, Diab F, Gil SR, et al. MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader subunits and cause Cornelia de Lange syndrome. Cell Reports. 2020;31(7). doi:10.1016/j.celrep.2020.107647","mla":"Parenti, Ilaria, et al. “MAU2 and NIPBL Variants Impair the Heterodimerization of the Cohesin Loader Subunits and Cause Cornelia de Lange Syndrome.” Cell Reports, vol. 31, no. 7, 107647, Elsevier, 2020, doi:10.1016/j.celrep.2020.107647."}},{"language":[{"iso":"eng"}],"file":[{"success":1,"checksum":"67db0251b1d415ae59005f876fcf9e34","file_id":"8805","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"2020_TrendsNeuroscience_Parenti.pdf","date_created":"2020-11-25T09:43:40Z","creator":"dernst","file_size":1439550,"date_updated":"2020-11-25T09:43:40Z"}],"publication_status":"published","publication_identifier":{"issn":["01662236"],"eissn":["1878108X"]},"ec_funded":1,"issue":"8","volume":43,"pmid":1,"oa_version":"Published Version","abstract":[{"lang":"eng","text":"Neurodevelopmental disorders (NDDs) are a class of disorders affecting brain development and function and are characterized by wide genetic and clinical variability. In this review, we discuss the multiple factors that influence the clinical presentation of NDDs, with particular attention to gene vulnerability, mutational load, and the two-hit model. Despite the complex architecture of\r\nmutational events associated with NDDs, the various proteins involved appear to converge on common pathways, such as synaptic plasticity/function, chromatin remodelers and the mammalian target of rapamycin (mTOR) pathway. A thorough understanding of the mechanisms behind these pathways will hopefully lead to the identification of candidates that could be targeted for treatment approaches."}],"intvolume":" 43","month":"08","scopus_import":"1","ddc":["570"],"date_updated":"2023-08-21T08:25:31Z","file_date_updated":"2020-11-25T09:43:40Z","department":[{"_id":"GaNo"}],"_id":"7957","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","article_type":"original","publication":"Trends in Neurosciences","day":"01","year":"2020","isi":1,"has_accepted_license":"1","date_created":"2020-06-14T22:00:49Z","doi":"10.1016/j.tins.2020.05.004","date_published":"2020-08-01T00:00:00Z","page":"608-621","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.","oa":1,"quality_controlled":"1","publisher":"Elsevier","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"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.","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","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","short":"I. Parenti, L.E. Garcia Rabaneda, H. Schön, G. Novarino, Trends in Neurosciences 43 (2020) 608–621.","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.","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.","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."},"title":"Neurodevelopmental disorders: From genetics to functional pathways","external_id":{"isi":["000553090600008"],"pmid":["32507511"]},"article_processing_charge":"No","author":[{"id":"D93538B0-5B71-11E9-AC62-02EBE5697425","first_name":"Ilaria","full_name":"Parenti, Ilaria","last_name":"Parenti"},{"id":"33D1B084-F248-11E8-B48F-1D18A9856A87","first_name":"Luis E","last_name":"Garcia Rabaneda","full_name":"Garcia Rabaneda, Luis E"},{"last_name":"Schön","full_name":"Schön, Hanna","first_name":"Hanna","id":"C8E17EDC-D7AA-11E9-B7B7-45ECE5697425"},{"full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"}],"project":[{"grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"}]},{"oa":1,"publisher":"Institute of Science and Technology Austria","acknowledgement":"I would like to especially thank Armel Nicolas from the Proteomics and Christoph Sommer from the Bioimaging Facilities for the data analysis, and to thank the team of the Preclinical Facility, especially Sabina Deixler, Angela Schlerka, Anita Lepold, Mihalea Mihai and Michael Schun for taking care of the mouse line maintenance and their great support.","date_created":"2020-10-07T14:53:13Z","doi":"10.15479/AT:ISTA:8620","date_published":"2020-10-12T00:00:00Z","page":"138","day":"12","year":"2020","has_accepted_license":"1","project":[{"grant_number":"W1232-B24","name":"Molecular Drug Targets","_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"_id":"05A0D778-7A3F-11EA-A408-12923DDC885E","grant_number":"F07807","name":"Neural stem cells in autism and epilepsy"}],"title":"Illuminating the role of Cul3 in autism spectrum disorder pathogenesis","article_processing_charge":"No","author":[{"last_name":"Morandell","full_name":"Morandell, Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","first_name":"Jasmin"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"mla":"Morandell, Jasmin. Illuminating the Role of Cul3 in Autism Spectrum Disorder Pathogenesis. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8620.","ieee":"J. Morandell, “Illuminating the role of Cul3 in autism spectrum disorder pathogenesis,” Institute of Science and Technology Austria, 2020.","short":"J. Morandell, Illuminating the Role of Cul3 in Autism Spectrum Disorder Pathogenesis, Institute of Science and Technology Austria, 2020.","apa":"Morandell, J. (2020). Illuminating the role of Cul3 in autism spectrum disorder pathogenesis. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8620","ama":"Morandell J. Illuminating the role of Cul3 in autism spectrum disorder pathogenesis. 2020. doi:10.15479/AT:ISTA:8620","chicago":"Morandell, Jasmin. “Illuminating the Role of Cul3 in Autism Spectrum Disorder Pathogenesis.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8620.","ista":"Morandell J. 2020. Illuminating the role of Cul3 in autism spectrum disorder pathogenesis. Institute of Science and Technology Austria."},"month":"10","alternative_title":["ISTA Thesis"],"oa_version":"Published Version","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"abstract":[{"lang":"eng","text":"The development of the human brain occurs through a tightly regulated series of dynamic and adaptive processes during prenatal and postnatal life. A disruption of this strictly orchestrated series of events can lead to a number of neurodevelopmental conditions, including Autism Spectrum Disorders (ASDs). ASDs are a very common, etiologically and phenotypically heterogeneous group of disorders sharing the core symptoms of social interaction and communication deficits and restrictive and repetitive interests and behaviors. They are estimated to affect one in 59 individuals in the U.S. and, over the last three decades, mutations in more than a hundred genetic loci have been convincingly linked to ASD pathogenesis. Yet, for the vast majority of these ASD-risk genes their role during brain development and precise molecular function still remain elusive.\r\nDe novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin 3 (CUL3) lead to ASD. In the study described here, we used Cul3 mouse models to evaluate the consequences of Cul3 mutations in vivo. Our results show that Cul3 heterozygous knockout mice exhibit deficits in motor coordination as well as ASD-relevant social and cognitive impairments. Cul3+/-, Cul3+/fl Emx1-Cre and Cul3fl/fl Emx1-Cre mutant brains display cortical lamination abnormalities due to defective migration of post-mitotic excitatory neurons, as well as reduced numbers of excitatory and inhibitory neurons. In line with the observed abnormal cortical organization, Cul3 heterozygous deletion is associated with decreased spontaneous excitatory and inhibitory activity in the cortex. At the molecular level we show that Cul3 regulates cytoskeletal and adhesion protein abundance in the mouse embryonic cortex. Abnormal regulation of cytoskeletal proteins in Cul3 mutant neural cells results in atypical organization of the actin mesh at the cell leading edge. Of note, heterozygous deletion of Cul3 in adult mice does not induce the majority of the behavioral defects observed in constitutive Cul3 haploinsufficient animals, pointing to a critical time-window for Cul3 deficiency.\r\nIn conclusion, our data indicate that Cul3 plays a critical role in the regulation of cytoskeletal proteins and neuronal migration. ASD-associated defects and behavioral abnormalities are primarily due to dosage sensitive Cul3 functions at early brain developmental stages."}],"related_material":{"record":[{"relation":"part_of_dissertation","id":"7800","status":"public"},{"relation":"part_of_dissertation","id":"8131","status":"public"}]},"language":[{"iso":"eng"}],"file":[{"file_name":"Jasmin_Morandell_Thesis-2020_final.pdf","date_created":"2020-10-07T14:41:49Z","creator":"jmorande","file_size":16155786,"date_updated":"2021-10-16T22:30:04Z","embargo":"2021-10-15","checksum":"7ee83e42de3e5ce2fedb44dff472f75f","file_id":"8621","relation":"main_file","access_level":"open_access","content_type":"application/pdf"},{"checksum":"5e0464af453734210ce7aab7b4a92e3a","file_id":"8622","embargo_to":"open_access","content_type":"application/x-zip-compressed","relation":"source_file","access_level":"closed","file_name":"Jasmin_Morandell_Thesis-2020_final.zip","date_created":"2020-10-07T14:45:07Z","file_size":24344152,"date_updated":"2021-10-16T22:30:04Z","creator":"jmorande"}],"publication_status":"published","degree_awarded":"PhD","publication_identifier":{"issn":["2663-337X"]},"status":"public","type":"dissertation","_id":"8620","department":[{"_id":"GaNo"}],"file_date_updated":"2021-10-16T22:30:04Z","ddc":["610"],"date_updated":"2023-09-07T13:22:14Z","supervisor":[{"orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","last_name":"Novarino","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"}]},{"publisher":"Cold Spring Harbor Laboratory","oa":1,"doi":"10.1101/2020.01.10.902064 ","date_published":"2020-01-11T00:00:00Z","date_created":"2020-05-05T14:31:33Z","has_accepted_license":"1","year":"2020","day":"11","publication":"bioRxiv","project":[{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"I03600","name":"Optical control of synaptic function via adhesion molecules"},{"_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Molecular Drug Targets","grant_number":"W1232-B24"}],"author":[{"last_name":"Morandell","full_name":"Morandell, Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","first_name":"Jasmin"},{"last_name":"Schwarz","full_name":"Schwarz, Lena A","first_name":"Lena A","id":"29A8453C-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","last_name":"Basilico","full_name":"Basilico, Bernadette","orcid":"0000-0003-1843-3173"},{"orcid":"0000-0003-1671-393X","full_name":"Tasciyan, Saren","last_name":"Tasciyan","id":"4323B49C-F248-11E8-B48F-1D18A9856A87","first_name":"Saren"},{"id":"2A103192-F248-11E8-B48F-1D18A9856A87","first_name":"Armel","full_name":"Nicolas, Armel","last_name":"Nicolas"},{"last_name":"Sommer","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M"},{"last_name":"Kreuzinger","full_name":"Kreuzinger, Caroline","first_name":"Caroline","id":"382077BA-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Knaus, Lisa","last_name":"Knaus","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","first_name":"Lisa"},{"last_name":"Dobler","full_name":"Dobler, Zoe","id":"D23090A2-9057-11EA-883A-A8396FC7A38F","first_name":"Zoe"},{"first_name":"Emanuele","full_name":"Cacci, Emanuele","last_name":"Cacci"},{"first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G","last_name":"Danzl"},{"last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia"}],"article_processing_charge":"No","title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","citation":{"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 ","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 ","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.","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 .","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 .","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 ."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","month":"01","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."}],"acknowledged_ssus":[{"_id":"PreCl"}],"oa_version":"Preprint","related_material":{"record":[{"relation":"later_version","id":"9429","status":"public"},{"relation":"dissertation_contains","status":"public","id":"8620"}]},"publication_status":"submitted","file":[{"checksum":"c6799ab5daba80efe8e2ed63c15f8c81","file_id":"7801","access_level":"open_access","relation":"main_file","content_type":"application/pdf","date_created":"2020-05-05T14:31:19Z","file_name":"2020.01.10.902064v1.full.pdf","creator":"rsix","date_updated":"2020-07-14T12:48:03Z","file_size":2931370}],"language":[{"iso":"eng"}],"type":"preprint","tmp":{"short":"CC BY-NC-ND (4.0)","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","image":"/images/cc_by_nc_nd.png"},"status":"public","_id":"7800","file_date_updated":"2020-07-14T12:48:03Z","department":[{"_id":"JoDa"},{"_id":"GaNo"},{"_id":"LifeSc"}],"date_updated":"2024-03-27T23:30:14Z","ddc":["570"]},{"page":"126-137","date_created":"2020-07-19T22:00:58Z","doi":"10.1016/j.gde.2020.06.004","date_published":"2020-12-01T00:00:00Z","year":"2020","has_accepted_license":"1","isi":1,"publication":"Current Opinion in Genetics and Development","day":"01","oa":1,"publisher":"Elsevier","quality_controlled":"1","external_id":{"pmid":["32659636"],"isi":["000598918900019"]},"article_processing_charge":"Yes (via OA deal)","author":[{"first_name":"Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","orcid":"0000-0003-1843-3173","full_name":"Basilico, Bernadette","last_name":"Basilico"},{"last_name":"Morandell","full_name":"Morandell, Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","first_name":"Jasmin"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"}],"title":"Molecular mechanisms for targeted ASD treatments","citation":{"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.","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","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","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.","short":"B. Basilico, J. Morandell, G. Novarino, Current Opinion in Genetics and Development 65 (2020) 126–137.","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.","ista":"Basilico B, Morandell J, Novarino G. 2020. Molecular mechanisms for targeted ASD treatments. Current Opinion in Genetics and Development. 65(12), 126–137."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","project":[{"call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425","name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411"},{"call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24","name":"Molecular Drug Targets"},{"name":"Neural stem cells in autism and epilepsy","grant_number":"F07807","_id":"05A0D778-7A3F-11EA-A408-12923DDC885E"}],"ec_funded":1,"volume":65,"related_material":{"record":[{"status":"public","id":"8620","relation":"dissertation_contains"}]},"issue":"12","publication_status":"published","publication_identifier":{"eissn":["18790380"],"issn":["0959437X"]},"language":[{"iso":"eng"}],"file":[{"success":1,"file_id":"8146","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"2020_CurrentOpGenetics_Basilico.pdf","date_created":"2020-07-22T06:47:45Z","creator":"dernst","file_size":1381545,"date_updated":"2020-07-22T06:47:45Z"}],"scopus_import":"1","intvolume":" 65","month":"12","abstract":[{"text":"The possibility to generate construct valid animal models enabled the development and testing of therapeutic strategies targeting the core features of autism spectrum disorders (ASDs). At the same time, these studies highlighted the necessity of identifying sensitive developmental time windows for successful therapeutic interventions. Animal and human studies also uncovered the possibility to stratify the variety of ASDs in molecularly distinct subgroups, potentially facilitating effective treatment design. Here, we focus on the molecular pathways emerging as commonly affected by mutations in diverse ASD-risk genes, on their role during critical windows of brain development and the potential treatments targeting these biological processes.","lang":"eng"}],"oa_version":"Published Version","pmid":1,"file_date_updated":"2020-07-22T06:47:45Z","department":[{"_id":"GaNo"}],"date_updated":"2024-03-27T23:30:14Z","ddc":["570"],"tmp":{"short":"CC BY-NC-ND (4.0)","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","image":"/images/cc_by_nc_nd.png"},"article_type":"original","type":"journal_article","status":"public","_id":"8131"},{"author":[{"first_name":"Ashley","full_name":"Marsh, Ashley","last_name":"Marsh"},{"first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino"},{"first_name":"Paul","last_name":"Lockhart","full_name":"Lockhart, Paul"},{"first_name":"Richard","full_name":"Leventer, Richard","last_name":"Leventer"}],"publist_id":"7949","external_id":{"pmid":["30089829"],"isi":["000454111500019"]},"article_processing_charge":"No","title":"CUGC for pontocerebellar hypoplasia type 9 and spastic paraplegia-63","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.","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.","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.","short":"A. Marsh, G. Novarino, P. Lockhart, R. Leventer, European Journal of Human Genetics 27 (2019) 161–166.","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","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"},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","page":"161-166","date_published":"2019-01-01T00:00:00Z","doi":"10.1038/s41431-018-0231-2","date_created":"2018-12-11T11:44:39Z","isi":1,"year":"2019","day":"01","publication":"European Journal of Human Genetics","quality_controlled":"1","publisher":"Springer Nature","oa":1,"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.","department":[{"_id":"GaNo"}],"date_updated":"2023-08-24T14:28:24Z","type":"journal_article","article_type":"original","status":"public","_id":"105","volume":27,"publication_status":"published","language":[{"iso":"eng"}],"scopus_import":"1","main_file_link":[{"url":"https://doi.org/10.1038/s41431-018-0231-2","open_access":"1"}],"month":"01","intvolume":" 27","abstract":[{"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.","lang":"eng"}],"pmid":1,"oa_version":"Published Version"},{"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"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.","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.","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","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","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.","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.","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."},"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","author":[{"first_name":"Alexander","last_name":"Traxl","full_name":"Traxl, Alexander"},{"last_name":"Mairinger","full_name":"Mairinger, Severin","first_name":"Severin"},{"first_name":"Thomas","full_name":"Filip, Thomas","last_name":"Filip"},{"first_name":"Michael","full_name":"Sauberer, Michael","last_name":"Sauberer"},{"last_name":"Stanek","full_name":"Stanek, Johann","first_name":"Johann"},{"full_name":"Poschner, Stefan","last_name":"Poschner","first_name":"Stefan"},{"first_name":"Walter","last_name":"Jäger","full_name":"Jäger, Walter"},{"full_name":"Zoufal, Viktoria","last_name":"Zoufal","first_name":"Viktoria"},{"full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Tournier, Nicolas","last_name":"Tournier","first_name":"Nicolas"},{"last_name":"Bauer","full_name":"Bauer, Martin","first_name":"Martin"},{"first_name":"Thomas","full_name":"Wanek, Thomas","last_name":"Wanek"},{"first_name":"Oliver","full_name":"Langer, Oliver","last_name":"Langer"}],"article_processing_charge":"No","external_id":{"isi":["000460600400031"],"pmid":["30694684"]},"day":"04","publication":"Molecular Pharmaceutics","isi":1,"year":"2019","date_published":"2019-03-04T00:00:00Z","doi":"10.1021/acs.molpharmaceut.8b01217","date_created":"2019-03-10T22:59:19Z","page":"1282-1293","quality_controlled":"1","publisher":"American Chemical Society","date_updated":"2023-08-25T08:02:51Z","department":[{"_id":"GaNo"}],"_id":"6088","status":"public","type":"journal_article","language":[{"iso":"eng"}],"publication_status":"published","issue":"3","volume":16,"pmid":1,"oa_version":"None","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."}],"month":"03","intvolume":" 16","scopus_import":"1"},{"type":"journal_article","article_type":"original","status":"public","_id":"6470","department":[{"_id":"GaNo"}],"date_updated":"2023-08-25T10:34:15Z","scopus_import":"1","main_file_link":[{"url":"https://doi.org/10.1113/JP277681","open_access":"1"}],"month":"06","intvolume":" 597","abstract":[{"text":"Investigating neuronal activity using genetically encoded Ca2+ indicators in behaving animals is hampered by inaccuracies in spike inference from fluorescent tracers. Here we combine two‐photon [Ca2+] imaging with cell‐attached recordings, followed by post hoc determination of the expression level of GCaMP6f, to explore how it affects the amplitude, kinetics and temporal summation of somatic [Ca2+] transients in mouse hippocampal pyramidal cells (PCs). The amplitude of unitary [Ca2+] transients (evoked by a single action potential) negatively correlates with GCaMP6f expression, but displays large variability even among PCs with similarly low expression levels. The summation of fluorescence signals is frequency‐dependent, supralinear and also shows remarkable cell‐to‐cell variability. We performed experimental data‐based simulations and found that spike inference error rates using MLspike depend strongly on unitary peak amplitudes and GCaMP6f expression levels. We provide simple methods for estimating the unitary [Ca2+] transients in individual weakly GCaMP6f‐expressing PCs, with which we achieve spike inference error rates of ∼5%. ","lang":"eng"}],"oa_version":"Published Version","pmid":1,"issue":"11","volume":597,"publication_identifier":{"eissn":["14697793"],"issn":["00223751"]},"publication_status":"published","language":[{"iso":"eng"}],"author":[{"full_name":"Éltes, Tímea","last_name":"Éltes","first_name":"Tímea"},{"first_name":"Miklos","last_name":"Szoboszlay","full_name":"Szoboszlay, Miklos"},{"last_name":"Szigeti","orcid":"0000-0001-9500-8758","full_name":"Szigeti, Margit Katalin","first_name":"Margit Katalin","id":"44F4BDC0-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Zoltan","last_name":"Nusser","full_name":"Nusser, Zoltan"}],"article_processing_charge":"No","external_id":{"pmid":["31006863"],"isi":["000470780400013"]},"title":"Improved spike inference accuracy by estimating the peak amplitude of unitary [Ca2+] transients in weakly GCaMP6f-expressing hippocampal pyramidal cells","citation":{"mla":"Éltes, Tímea, et al. “Improved Spike Inference Accuracy by Estimating the Peak Amplitude of Unitary [Ca2+] Transients in Weakly GCaMP6f-Expressing Hippocampal Pyramidal Cells.” Journal of Physiology, vol. 597, no. 11, Wiley, 2019, pp. 2925–2947, doi:10.1113/JP277681.","ieee":"T. Éltes, M. Szoboszlay, M. K. Szigeti, and Z. Nusser, “Improved spike inference accuracy by estimating the peak amplitude of unitary [Ca2+] transients in weakly GCaMP6f-expressing hippocampal pyramidal cells,” Journal of Physiology, vol. 597, no. 11. Wiley, pp. 2925–2947, 2019.","short":"T. Éltes, M. Szoboszlay, M.K. Szigeti, Z. Nusser, Journal of Physiology 597 (2019) 2925–2947.","apa":"Éltes, T., Szoboszlay, M., Szigeti, M. K., & Nusser, Z. (2019). Improved spike inference accuracy by estimating the peak amplitude of unitary [Ca2+] transients in weakly GCaMP6f-expressing hippocampal pyramidal cells. Journal of Physiology. Wiley. https://doi.org/10.1113/JP277681","ama":"Éltes T, Szoboszlay M, Szigeti MK, Nusser Z. Improved spike inference accuracy by estimating the peak amplitude of unitary [Ca2+] transients in weakly GCaMP6f-expressing hippocampal pyramidal cells. Journal of Physiology. 2019;597(11):2925–2947. doi:10.1113/JP277681","chicago":"Éltes, Tímea, Miklos Szoboszlay, Margit Katalin Szigeti, and Zoltan Nusser. “Improved Spike Inference Accuracy by Estimating the Peak Amplitude of Unitary [Ca2+] Transients in Weakly GCaMP6f-Expressing Hippocampal Pyramidal Cells.” Journal of Physiology. Wiley, 2019. https://doi.org/10.1113/JP277681.","ista":"Éltes T, Szoboszlay M, Szigeti MK, Nusser Z. 2019. Improved spike inference accuracy by estimating the peak amplitude of unitary [Ca2+] transients in weakly GCaMP6f-expressing hippocampal pyramidal cells. Journal of Physiology. 597(11), 2925–2947."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","publisher":"Wiley","quality_controlled":"1","oa":1,"page":"2925–2947","date_published":"2019-06-01T00:00:00Z","doi":"10.1113/JP277681","date_created":"2019-05-19T21:59:17Z","isi":1,"year":"2019","day":"01","publication":"Journal of Physiology"},{"intvolume":" 1724","month":"12","scopus_import":"1","pmid":1,"oa_version":"None","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"}],"volume":1724,"language":[{"iso":"eng"}],"publication_status":"published","publication_identifier":{"eissn":["18726240"],"issn":["00068993"]},"status":"public","article_type":"original","type":"journal_article","_id":"6896","department":[{"_id":"GaNo"}],"date_updated":"2023-08-30T06:19:49Z","publisher":"Elsevier","quality_controlled":"1","date_created":"2019-09-22T22:00:35Z","doi":"10.1016/j.brainres.2019.146458","date_published":"2019-12-01T00:00:00Z","publication":"Brain Research","day":"01","year":"2019","isi":1,"article_number":"146458","title":"Modeling cell-cell interactions in the brain using cerebral organoids","external_id":{"pmid":["31521639"],"isi":["000491646600033"]},"article_processing_charge":"No","author":[{"last_name":"Oliveira","full_name":"Oliveira, Bárbara","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","first_name":"Bárbara"},{"full_name":"Yahya, Aysan Çerağ","last_name":"Yahya","first_name":"Aysan Çerağ","id":"365A65F8-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"ista":"Oliveira B, Yahya AÇ, Novarino G. 2019. Modeling cell-cell interactions in the brain using cerebral organoids. Brain Research. 1724, 146458.","chicago":"Oliveira, Bárbara, Aysan Çerağ Yahya, and Gaia Novarino. “Modeling Cell-Cell Interactions in the Brain Using Cerebral Organoids.” Brain Research. Elsevier, 2019. https://doi.org/10.1016/j.brainres.2019.146458.","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","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.","short":"B. Oliveira, A.Ç. Yahya, G. Novarino, Brain Research 1724 (2019).","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."}},{"oa_version":"None","publisher":"Elsevier","quality_controlled":"1","month":"12","intvolume":" 29","isi":1,"publication_identifier":{"issn":["0924-977X"]},"year":"2019","publication_status":"published","day":"13","publication":"European Neuropsychopharmacology","language":[{"iso":"eng"}],"page":"S11-S12","doi":"10.1016/j.euroneuro.2019.09.040","issue":"Supplement 6","volume":29,"date_published":"2019-12-13T00:00:00Z","date_created":"2020-01-30T10:07:41Z","_id":"7415","type":"journal_article","article_type":"original","status":"public","citation":{"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.","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","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.","short":"J. Morandell, A. Nicolas, L.A. Schwarz, G. Novarino, European Neuropsychopharmacology 29 (2019) S11–S12.","chicago":"Morandell, Jasmin, Armel Nicolas, Lena A Schwarz, and Gaia Novarino. “S.16.05 Illuminating the Role of the E3 Ubiquitin Ligase Cullin3 in Brain Development and Autism.” European Neuropsychopharmacology. Elsevier, 2019. https://doi.org/10.1016/j.euroneuro.2019.09.040.","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."},"date_updated":"2023-09-07T14:56:17Z","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","author":[{"first_name":"Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","full_name":"Morandell, Jasmin","last_name":"Morandell"},{"first_name":"Armel","id":"2A103192-F248-11E8-B48F-1D18A9856A87","full_name":"Nicolas, Armel","last_name":"Nicolas"},{"full_name":"Schwarz, Lena A","last_name":"Schwarz","id":"29A8453C-F248-11E8-B48F-1D18A9856A87","first_name":"Lena A"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","last_name":"Novarino"}],"article_processing_charge":"No","external_id":{"isi":["000502657500021"]},"department":[{"_id":"GaNo"},{"_id":"LifeSc"}],"title":"S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism"},{"page":"S11","date_published":"2019-12-13T00:00:00Z","doi":"10.1016/j.euroneuro.2019.09.039","volume":29,"issue":"Supplement 6","date_created":"2020-01-30T10:06:15Z","isi":1,"publication_identifier":{"issn":["0924-977X"]},"publication_status":"published","year":"2019","day":"13","publication":"European Neuropsychopharmacology","language":[{"iso":"eng"}],"quality_controlled":"1","publisher":"Elsevier","month":"12","intvolume":" 29","oa_version":"None","author":[{"first_name":"Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","last_name":"Knaus","full_name":"Knaus, Lisa"},{"full_name":"Tarlungeanu, Dora-Clara","last_name":"Tarlungeanu","first_name":"Dora-Clara","id":"2ABCE612-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"}],"article_processing_charge":"No","external_id":{"isi":["000502657500020"]},"department":[{"_id":"GaNo"}],"title":"S.16.03 A homozygous missense mutation in SLC7A5 leads to autism spectrum disorder and microcephaly","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.","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.","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","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","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.","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."},"date_updated":"2023-09-07T14:55:23Z","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","type":"journal_article","article_type":"original","status":"public","_id":"7414"},{"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["570"],"date_updated":"2024-02-21T13:41:01Z","citation":{"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).","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","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.","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."},"file_date_updated":"2020-07-14T12:47:18Z","title":"Supplementary data for the research paper \"Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition\"","department":[{"_id":"GaNo"}],"author":[{"first_name":"Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","full_name":"Dotter, Christoph","orcid":"0000-0002-9033-9096","last_name":"Dotter"},{"last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"}],"article_processing_charge":"No","_id":"6074","status":"public","type":"research_data","file":[{"checksum":"bc1b285edca9e98a2c63d153c79bb75b","file_id":"6084","access_level":"open_access","relation":"supplementary_material","content_type":"application/zip","date_created":"2019-03-07T13:37:19Z","file_name":"Setd5_paper.zip","creator":"dernst","date_updated":"2020-07-14T12:47:18Z","file_size":33202743}],"day":"09","has_accepted_license":"1","year":"2019","date_published":"2019-01-09T00:00:00Z","doi":"10.15479/AT:ISTA:6074","related_material":{"record":[{"relation":"research_paper","status":"public","id":"3"}]},"date_created":"2019-03-07T13:32:35Z","oa_version":"Published Version","abstract":[{"lang":"eng","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."}],"month":"01","publisher":"Institute of Science and Technology Austria","oa":1},{"issue":"423","volume":10,"date_published":"2018-01-10T00:00:00Z","doi":"10.1126/scitranslmed.aar7514","date_created":"2018-12-11T11:46:34Z","publication_status":"published","year":"2018","day":"10","language":[{"iso":"eng"}],"publication":"Science Translational Medicine","quality_controlled":"1","scopus_import":1,"publisher":"American Association for the Advancement of Science","month":"01","intvolume":" 10","abstract":[{"lang":"eng","text":"Inhibition of the endoplasmic reticulum stress pathway may hold the key to Zika virus-associated microcephaly treatment. "}],"oa_version":"None","publist_id":"7365","author":[{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"}],"title":"Zika-associated microcephaly: Reduce the stress and race for the treatment","department":[{"_id":"GaNo"}],"date_updated":"2021-01-12T07:59:42Z","citation":{"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.","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.","short":"G. Novarino, Science Translational Medicine 10 (2018).","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","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","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.","ista":"Novarino G. 2018. Zika-associated microcephaly: Reduce the stress and race for the treatment. Science Translational Medicine. 10(423), eaar7514."},"user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","type":"journal_article","status":"public","_id":"456","article_number":"eaar7514"},{"article_number":"100","title":"Genomics in neurodevelopmental disorders: an avenue to personalized medicine","author":[{"full_name":"Tarlungeanu, Dora-Clara","last_name":"Tarlungeanu","id":"2ABCE612-F248-11E8-B48F-1D18A9856A87","first_name":"Dora-Clara"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178"}],"external_id":{"isi":["000441266700006"],"pmid":["30089840"]},"article_processing_charge":"No","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"short":"D.-C. Tarlungeanu, G. Novarino, Experimental & Molecular Medicine 50 (2018).","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.","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","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","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.","ista":"Tarlungeanu D-C, Novarino G. 2018. Genomics in neurodevelopmental disorders: an avenue to personalized medicine. Experimental & Molecular Medicine. 50(8), 100.","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."},"quality_controlled":"1","publisher":"Springer Nature","oa":1,"doi":"10.1038/s12276-018-0129-7","date_published":"2018-08-07T00:00:00Z","date_created":"2019-01-27T22:59:11Z","day":"07","publication":"Experimental & Molecular Medicine","isi":1,"has_accepted_license":"1","year":"2018","status":"public","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"_id":"5888","file_date_updated":"2020-07-14T12:47:13Z","department":[{"_id":"GaNo"}],"ddc":["570"],"date_updated":"2023-09-11T14:04:41Z","month":"08","intvolume":" 50","scopus_import":"1","pmid":1,"oa_version":"Published Version","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."}],"issue":"8","volume":50,"file":[{"creator":"dernst","date_updated":"2020-07-14T12:47:13Z","file_size":1237482,"date_created":"2019-01-28T15:18:02Z","file_name":"2018_EMM_Tarlungeanu.pdf","access_level":"open_access","relation":"main_file","content_type":"application/pdf","checksum":"4498301c8c53097c9a1a8ef990936eb5","file_id":"5893"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["2092-6413"]},"publication_status":"published"},{"title":"Neural stem cells in neuropsychiatric disorders","author":[{"last_name":"Sacco","full_name":"Sacco, Roberto","id":"42C9F57E-F248-11E8-B48F-1D18A9856A87","first_name":"Roberto"},{"first_name":"Emanuele","full_name":"Cacci, Emanuele","last_name":"Cacci"},{"last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"}],"publist_id":"7268","article_processing_charge":"No","external_id":{"isi":["000427101600018"]},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"ista":"Sacco R, Cacci E, Novarino G. 2018. Neural stem cells in neuropsychiatric disorders. Current Opinion in Neurobiology. 48(2), 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.","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","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","short":"R. Sacco, E. Cacci, G. Novarino, Current Opinion in Neurobiology 48 (2018) 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.","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."},"date_published":"2018-02-01T00:00:00Z","doi":"10.1016/j.conb.2017.12.005","date_created":"2018-12-11T11:47:06Z","page":"131 - 138","day":"01","publication":"Current Opinion in Neurobiology","isi":1,"year":"2018","quality_controlled":"1","publisher":"Elsevier","department":[{"_id":"GaNo"}],"date_updated":"2023-09-13T09:01:56Z","status":"public","type":"journal_article","_id":"546","issue":"2","volume":48,"language":[{"iso":"eng"}],"publication_status":"published","month":"02","intvolume":" 48","scopus_import":"1","oa_version":"None","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."}]},{"status":"public","type":"journal_article","article_type":"original","_id":"691","department":[{"_id":"GaNo"}],"date_updated":"2023-10-16T09:55:43Z","intvolume":" 55","month":"01","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056005/","open_access":"1"}],"scopus_import":"1","oa_version":"Submitted Version","pmid":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"}],"volume":55,"issue":"1","language":[{"iso":"eng"}],"publication_status":"published","publication_identifier":{"issn":["0022-2593"]},"project":[{"_id":"254BA948-B435-11E9-9278-68D0E5697425","grant_number":"401299","name":"Probing development and reversibility of autism spectrum disorders"}],"title":"A homozygous founder mutation in TRAPPC6B associates with a neurodevelopmental disorder characterised by microcephaly epilepsy and autistic features","external_id":{"isi":["000418199800007"],"pmid":["28626029"]},"article_processing_charge":"No","publist_id":"7016","author":[{"first_name":"Isaac","full_name":"Marin Valencia, Isaac","last_name":"Marin Valencia"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"},{"full_name":"Johansen, Anide","last_name":"Johansen","first_name":"Anide"},{"last_name":"Rosti","full_name":"Rosti, Başak","first_name":"Başak"},{"last_name":"Issa","full_name":"Issa, Mahmoud","first_name":"Mahmoud"},{"first_name":"Damir","full_name":"Musaev, Damir","last_name":"Musaev"},{"full_name":"Bhat, Gifty","last_name":"Bhat","first_name":"Gifty"},{"first_name":"Eric","last_name":"Scott","full_name":"Scott, Eric"},{"last_name":"Silhavy","full_name":"Silhavy, Jennifer","first_name":"Jennifer"},{"full_name":"Stanley, Valentina","last_name":"Stanley","first_name":"Valentina"},{"first_name":"Rasim","full_name":"Rosti, Rasim","last_name":"Rosti"},{"first_name":"Jeremy","full_name":"Gleeson, Jeremy","last_name":"Gleeson"},{"first_name":"Farhad","last_name":"Imam","full_name":"Imam, Farhad"},{"first_name":"Maha","last_name":"Zaki","full_name":"Zaki, Maha"},{"first_name":"Joseph","full_name":"Gleeson, Joseph","last_name":"Gleeson"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"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.","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.","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","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","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.","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.","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."},"oa":1,"publisher":"BMJ Publishing Group","quality_controlled":"1","date_created":"2018-12-11T11:47:57Z","date_published":"2018-01-01T00:00:00Z","doi":"10.1136/jmedgenet-2017-104627","page":"48 - 54","publication":"Journal of Medical Genetics","day":"01","year":"2018","isi":1},{"oa_version":"Published Version","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"EM-Fac"},{"_id":"Bio"}],"abstract":[{"text":"Autism spectrum disorders (ASD) are a group of genetic disorders often overlapping with other neurological conditions. Despite the remarkable number of scientific breakthroughs of the last 100 years, the treatment of neurodevelopmental disorders (e.g. autism spectrum disorder, intellectual disability, epilepsy) remains a great challenge. Recent advancements in geno mics, like whole-exome or whole-genome sequencing, have enabled scientists to identify numerous mutations underlying neurodevelopmental disorders. Given the few hundred risk genes that were discovered, the etiological variability and the heterogeneous phenotypic outcomes, the need for genotype -along with phenotype- based diagnosis of individual patients becomes a requisite. Driven by this rationale, in a previous study our group described mutations, identified via whole - exome sequencing, in the gene BCKDK – encoding for a key regulator of branched chain amin o acid (BCAA) catabolism - as a cause of ASD. Following up on the role of BCAAs, in the study described here we show that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid transporter localized mainly 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 neurolo gical abnormalities. Additionally, deletion of Slc7a5 from the neural progenitor cell population leads to microcephaly. Interestingly, we demonstrate that BCAA intracerebroventricular administration ameliorates abnormal behaviors in adult mutant mice. Furthermore, whole - exome sequencing of patients diagnosed with neurological dis o r ders helped us identify several patients with autistic traits, microcephaly and motor delay carrying deleterious homozygous mutations in the SLC7A5 gene. In conclusion, our data elucidate a neurological syndrome defined by SLC7A5 mutations and support an essential role for t he BCAA s in human bra in function. Together with r ecent studies (described in chapter two) that have successfully made the transition into clinical practice, our findings on the role of B CAAs might have a crucial impact on the development of novel individualized therapeutic strategies for ASD. ","lang":"eng"}],"month":"03","alternative_title":["ISTA Thesis"],"file":[{"creator":"dernst","date_updated":"2021-02-11T23:30:15Z","file_size":43684035,"date_created":"2019-04-05T09:19:17Z","file_name":"2018_Thesis_Tarlungeanu_source.docx","access_level":"closed","relation":"source_file","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","embargo_to":"open_access","file_id":"6217","checksum":"9f5231c96e0ad945040841a8630232da"},{"file_name":"2018_Thesis_Tarlungeanu.pdf","date_created":"2019-04-05T09:19:17Z","file_size":30511532,"date_updated":"2021-02-11T11:17:16Z","creator":"dernst","embargo":"2018-03-15","file_id":"6218","checksum":"0c33c370aa2010df5c552db57a6d01e9","content_type":"application/pdf","relation":"main_file","access_level":"open_access"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["2663-337X"]},"degree_awarded":"PhD","publication_status":"published","related_material":{"record":[{"status":"public","id":"1183","relation":"part_of_dissertation"}]},"_id":"395","status":"public","pubrep_id":"992","type":"dissertation","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"ddc":["570","616"],"supervisor":[{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino"}],"date_updated":"2023-09-07T12:38:59Z","department":[{"_id":"GaNo"}],"file_date_updated":"2021-02-11T23:30:15Z","publisher":"Institute of Science and Technology Austria","oa":1,"day":"01","has_accepted_license":"1","year":"2018","doi":"10.15479/AT:ISTA:th_992","date_published":"2018-03-01T00:00:00Z","date_created":"2018-12-11T11:46:14Z","page":"88","project":[{"grant_number":"F03523","name":"Transmembrane Transporters in Health and Disease","call_identifier":"FWF","_id":"25473368-B435-11E9-9278-68D0E5697425"}],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"ama":"Tarlungeanu D-C. The branched chain amino acids in autism spectrum disorders . 2018. doi:10.15479/AT:ISTA:th_992","apa":"Tarlungeanu, D.-C. (2018). The branched chain amino acids in autism spectrum disorders . Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_992","ieee":"D.-C. Tarlungeanu, “The branched chain amino acids in autism spectrum disorders ,” Institute of Science and Technology Austria, 2018.","short":"D.-C. Tarlungeanu, The Branched Chain Amino Acids in Autism Spectrum Disorders , Institute of Science and Technology Austria, 2018.","mla":"Tarlungeanu, Dora-Clara. The Branched Chain Amino Acids in Autism Spectrum Disorders . Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th_992.","ista":"Tarlungeanu D-C. 2018. The branched chain amino acids in autism spectrum disorders . Institute of Science and Technology Austria.","chicago":"Tarlungeanu, Dora-Clara. “The Branched Chain Amino Acids in Autism Spectrum Disorders .” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th_992."},"title":"The branched chain amino acids in autism spectrum disorders ","author":[{"full_name":"Tarlungeanu, Dora-Clara","last_name":"Tarlungeanu","id":"2ABCE612-F248-11E8-B48F-1D18A9856A87","first_name":"Dora-Clara"}],"publist_id":"7434","article_processing_charge":"No"},{"article_type":"original","type":"journal_article","pubrep_id":"1071","status":"public","_id":"3","file_date_updated":"2020-07-14T12:45:58Z","department":[{"_id":"GaNo"},{"_id":"EdHa"}],"date_updated":"2024-03-27T23:30:44Z","ddc":["570"],"scopus_import":"1","intvolume":" 21","month":"11","acknowledged_ssus":[{"_id":"M-Shop"},{"_id":"PreCl"}],"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"}],"oa_version":"Submitted Version","issue":"12","related_material":{"link":[{"description":"News on IST Homepage","url":"https://ist.ac.at/en/news/mutation-that-causes-autism-and-intellectual-disability-makes-brain-less-flexible/","relation":"press_release"}],"record":[{"relation":"popular_science","status":"public","id":"6074"},{"relation":"dissertation_contains","status":"public","id":"12364"}]},"volume":21,"publication_status":"published","language":[{"iso":"eng"}],"file":[{"file_name":"2017_NatureNeuroscience_Deliu.pdf","date_created":"2019-04-09T07:41:57Z","creator":"dernst","file_size":8167169,"date_updated":"2020-07-14T12:45:58Z","file_id":"6255","checksum":"60abd0f05b7cdc08a6b0ec460884084f","relation":"main_file","access_level":"open_access","content_type":"application/pdf"}],"project":[{"grant_number":"401299","name":"Probing development and reversibility of autism spectrum disorders","_id":"254BA948-B435-11E9-9278-68D0E5697425"}],"external_id":{"isi":["000451324700010"]},"article_processing_charge":"No","publist_id":"8054","author":[{"full_name":"Deliu, Elena","orcid":"0000-0002-7370-5293","last_name":"Deliu","first_name":"Elena","id":"37A40D7E-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Arecco","full_name":"Arecco, Niccoló","first_name":"Niccoló"},{"first_name":"Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","full_name":"Morandell, Jasmin","last_name":"Morandell"},{"id":"4C66542E-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph","last_name":"Dotter","full_name":"Dotter, Christoph","orcid":"0000-0002-9033-9096"},{"id":"475990FE-F248-11E8-B48F-1D18A9856A87","first_name":"Ximena","last_name":"Contreras","full_name":"Contreras, Ximena"},{"first_name":"Charles","full_name":"Girardot, Charles","last_name":"Girardot"},{"first_name":"Eva","full_name":"Käsper, Eva","last_name":"Käsper"},{"full_name":"Kozlova, Alena","last_name":"Kozlova","id":"C50A9596-02D0-11E9-976E-E38CFE5CBC1D","first_name":"Alena"},{"last_name":"Kishi","full_name":"Kishi, Kasumi","id":"3065DFC4-F248-11E8-B48F-1D18A9856A87","first_name":"Kasumi"},{"orcid":"0000-0002-9529-4464","full_name":"Chiaradia, Ilaria","last_name":"Chiaradia","id":"B6467F20-02D0-11E9-BDA5-E960C241894A","first_name":"Ilaria"},{"last_name":"Noh","full_name":"Noh, Kyung","first_name":"Kyung"},{"orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia"}],"title":"Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition","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.","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.","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.","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.","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","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."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","oa":1,"publisher":"Nature Publishing Group","quality_controlled":"1","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.","page":"1717 - 1727","date_created":"2018-12-11T11:44:05Z","date_published":"2018-11-19T00:00:00Z","doi":"10.1038/s41593-018-0266-2","year":"2018","has_accepted_license":"1","isi":1,"publication":"Nature Neuroscience","day":"19"},{"file":[{"content_type":"application/pdf","relation":"main_file","access_level":"open_access","checksum":"1aa20f19a1e90664fadce6e7d5284fdc","file_id":"4944","file_size":4106772,"date_updated":"2020-07-14T12:46:44Z","creator":"system","file_name":"IST-2018-931-v1+1_journal.ppat.1006758.pdf","date_created":"2018-12-12T10:12:26Z"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["15537366"]},"publication_status":"published","issue":"12","volume":13,"oa_version":"Published Version","abstract":[{"lang":"eng","text":"RNA-dependent RNA polymerases (RdRps) play a key role in the life cycle of RNA viruses and impact their immunobiology. The arenavirus lymphocytic choriomeningitis virus (LCMV) strain Clone 13 provides a benchmark model for studying chronic infection. A major genetic determinant for its ability to persist maps to a single amino acid exchange in the viral L protein, which exhibits RdRp activity, yet its functional consequences remain elusive. To unravel the L protein interactions with the host proteome, we engineered infectious L protein-tagged LCMV virions by reverse genetics. A subsequent mass-spectrometric analysis of L protein pulldowns from infected human cells revealed a comprehensive network of interacting host proteins. The obtained LCMV L protein interactome was bioinformatically integrated with known host protein interactors of RdRps from other RNA viruses, emphasizing interconnected modules of human proteins. Functional characterization of selected interactors highlighted proviral (DDX3X) as well as antiviral (NKRF, TRIM21) host factors. To corroborate these findings, we infected Trim21-/-mice with LCMV and found impaired virus control in chronic infection. These results provide insights into the complex interactions of the arenavirus LCMV and other viral RdRps with the host proteome and contribute to a better molecular understanding of how chronic viruses interact with their host."}],"month":"12","intvolume":" 13","scopus_import":1,"ddc":["576","616"],"date_updated":"2021-01-12T08:01:48Z","file_date_updated":"2020-07-14T12:46:44Z","department":[{"_id":"GaNo"}],"_id":"540","status":"public","pubrep_id":"931","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"day":"01","publication":"PLoS Pathogens","has_accepted_license":"1","year":"2017","doi":"10.1371/journal.ppat.1006758","date_published":"2017-12-01T00:00:00Z","date_created":"2018-12-11T11:47:03Z","publisher":"Public Library of Science","quality_controlled":"1","oa":1,"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"chicago":"Khamina, Kseniya, Alexander Lercher, Michael Caldera, Christopher Schliehe, Bojan Vilagos, Mehmet Sahin, Lindsay Kosack, et al. “Characterization of Host Proteins Interacting with the Lymphocytic Choriomeningitis Virus L Protein.” PLoS Pathogens. Public Library of Science, 2017. https://doi.org/10.1371/journal.ppat.1006758.","ista":"Khamina K, Lercher A, Caldera M, Schliehe C, Vilagos B, Sahin M, Kosack L, Bhattacharya A, Májek P, Stukalov A, Sacco R, James L, Pinschewer D, Bennett K, Menche J, Bergthaler A. 2017. Characterization of host proteins interacting with the lymphocytic choriomeningitis virus L protein. PLoS Pathogens. 13(12), e1006758.","mla":"Khamina, Kseniya, et al. “Characterization of Host Proteins Interacting with the Lymphocytic Choriomeningitis Virus L Protein.” PLoS Pathogens, vol. 13, no. 12, e1006758, Public Library of Science, 2017, doi:10.1371/journal.ppat.1006758.","short":"K. Khamina, A. Lercher, M. Caldera, C. Schliehe, B. Vilagos, M. Sahin, L. Kosack, A. Bhattacharya, P. Májek, A. Stukalov, R. Sacco, L. James, D. Pinschewer, K. Bennett, J. Menche, A. Bergthaler, PLoS Pathogens 13 (2017).","ieee":"K. Khamina et al., “Characterization of host proteins interacting with the lymphocytic choriomeningitis virus L protein,” PLoS Pathogens, vol. 13, no. 12. Public Library of Science, 2017.","apa":"Khamina, K., Lercher, A., Caldera, M., Schliehe, C., Vilagos, B., Sahin, M., … Bergthaler, A. (2017). Characterization of host proteins interacting with the lymphocytic choriomeningitis virus L protein. PLoS Pathogens. Public Library of Science. https://doi.org/10.1371/journal.ppat.1006758","ama":"Khamina K, Lercher A, Caldera M, et al. Characterization of host proteins interacting with the lymphocytic choriomeningitis virus L protein. PLoS Pathogens. 2017;13(12). doi:10.1371/journal.ppat.1006758"},"title":"Characterization of host proteins interacting with the lymphocytic choriomeningitis virus L protein","publist_id":"7276","author":[{"last_name":"Khamina","full_name":"Khamina, Kseniya","first_name":"Kseniya"},{"last_name":"Lercher","full_name":"Lercher, Alexander","first_name":"Alexander"},{"first_name":"Michael","full_name":"Caldera, Michael","last_name":"Caldera"},{"first_name":"Christopher","full_name":"Schliehe, Christopher","last_name":"Schliehe"},{"first_name":"Bojan","full_name":"Vilagos, Bojan","last_name":"Vilagos"},{"last_name":"Sahin","full_name":"Sahin, Mehmet","first_name":"Mehmet"},{"first_name":"Lindsay","full_name":"Kosack, Lindsay","last_name":"Kosack"},{"first_name":"Anannya","last_name":"Bhattacharya","full_name":"Bhattacharya, Anannya"},{"last_name":"Májek","full_name":"Májek, Peter","first_name":"Peter"},{"full_name":"Stukalov, Alexey","last_name":"Stukalov","first_name":"Alexey"},{"first_name":"Roberto","id":"42C9F57E-F248-11E8-B48F-1D18A9856A87","full_name":"Sacco, Roberto","last_name":"Sacco"},{"last_name":"James","full_name":"James, Leo","first_name":"Leo"},{"first_name":"Daniel","last_name":"Pinschewer","full_name":"Pinschewer, Daniel"},{"full_name":"Bennett, Keiryn","last_name":"Bennett","first_name":"Keiryn"},{"first_name":"Jörg","last_name":"Menche","full_name":"Menche, Jörg"},{"first_name":"Andreas","full_name":"Bergthaler, Andreas","last_name":"Bergthaler"}],"article_number":"e1006758"},{"status":"public","type":"book_chapter","_id":"623","series_title":"Advances in Anatomy Embryology and Cell Biology","department":[{"_id":"GaNo"}],"date_updated":"2021-01-12T08:06:46Z","month":"05","intvolume":" 224","alternative_title":["ADVSANAT"],"scopus_import":1,"oa_version":"None","abstract":[{"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.","lang":"eng"}],"volume":224,"language":[{"iso":"eng"}],"publication_identifier":{"issn":["03015556"],"isbn":["978-3-319-52496-2"]},"publication_status":"published","editor":[{"first_name":"Michael","last_name":"Schmeisser","full_name":"Schmeisser, Michael"},{"last_name":"Boekers","full_name":"Boekers, Tobias","first_name":"Tobias"}],"title":"Extracerebral dysfunction in animal models of autism spectrum disorder","publist_id":"7177","author":[{"full_name":"Hill Yardin, Elisa","last_name":"Hill Yardin","first_name":"Elisa"},{"first_name":"Sonja","last_name":"Mckeown","full_name":"Mckeown, Sonja"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178"},{"last_name":"Grabrucker","full_name":"Grabrucker, Andreas","first_name":"Andreas"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"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.","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.","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","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","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.","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.","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."},"quality_controlled":"1","publisher":"Springer","date_published":"2017-05-28T00:00:00Z","doi":"10.1007/978-3-319-52498-6_9","date_created":"2018-12-11T11:47:33Z","page":"159 - 187","day":"28","publication":"Translational Anatomy and Cell Biology of Autism Spectrum Disorder","year":"2017"},{"status":"public","type":"book_chapter","series_title":"Advances in Anatomy Embryology and Cell Biology","_id":"634","department":[{"_id":"GaNo"}],"date_updated":"2021-01-12T08:07:08Z","month":"05","intvolume":" 224","alternative_title":["ADVSANAT"],"scopus_import":1,"oa_version":"None","abstract":[{"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.","lang":"eng"}],"volume":224,"language":[{"iso":"eng"}],"publication_identifier":{"eisbn":["978-3-319-52498-6"]},"publication_status":"published","project":[{"name":"Transmembrane Transporters in Health and Disease","grant_number":"F03523","_id":"25473368-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"}],"title":"Genetic and pharmacological reversibility of phenotypes in mouse models of autism spectrum disorder","editor":[{"first_name":"Michael","last_name":"Schmeisser","full_name":"Schmeisser, Michael"},{"first_name":"Tobias","full_name":"Boekers, Tobias","last_name":"Boekers"}],"publist_id":"7156","author":[{"first_name":"Jan","full_name":"Schroeder, Jan","last_name":"Schroeder"},{"orcid":"0000-0002-7370-5293","full_name":"Deliu, Elena","last_name":"Deliu","id":"37A40D7E-F248-11E8-B48F-1D18A9856A87","first_name":"Elena"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","last_name":"Novarino"},{"full_name":"Schmeisser, Michael","last_name":"Schmeisser","first_name":"Michael"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","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.","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.","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.","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.","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","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"},"quality_controlled":"1","publisher":"Springer","doi":"10.1007/978-3-319-52498-6_10","date_published":"2017-05-28T00:00:00Z","date_created":"2018-12-11T11:47:37Z","page":"189 - 211","day":"28","publication":"Translational Anatomy and Cell Biology of Autism Spectrum Disorder","year":"2017"},{"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."}],"oa_version":"None","publisher":"American Association for the Advancement of Science","scopus_import":1,"quality_controlled":"1","intvolume":" 9","month":"03","year":"2017","publication_status":"published","publication_identifier":{"issn":["19466234"]},"publication":"Science Translational Medicine","language":[{"iso":"eng"}],"day":"15","date_created":"2018-12-11T11:47:45Z","issue":"381","doi":"10.1126/scitranslmed.aam9867","volume":9,"date_published":"2017-03-15T00:00:00Z","_id":"656","article_number":"eaam9867","type":"journal_article","status":"public","date_updated":"2021-01-12T08:07:59Z","citation":{"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.","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","ama":"Novarino G. Modeling Alzheimer’s disease in mice with human neurons. Science Translational Medicine. 2017;9(381). doi:10.1126/scitranslmed.aam9867","short":"G. Novarino, Science Translational Medicine 9 (2017).","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.","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.","ista":"Novarino G. 2017. Modeling Alzheimer’s disease in mice with human neurons. Science Translational Medicine. 9(381), eaam9867."},"user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","publist_id":"7079","author":[{"orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","last_name":"Novarino","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"}],"department":[{"_id":"GaNo"}],"title":"Modeling Alzheimer's disease in mice with human neurons"},{"oa_version":"None","abstract":[{"text":"Perinatal exposure to penicillin may result in longlasting gut and behavioral changes.","lang":"eng"}],"intvolume":" 9","month":"04","publisher":"American Association for the Advancement of Science","quality_controlled":"1","scopus_import":1,"publication":"Science Translational Medicine","language":[{"iso":"eng"}],"day":"26","publication_status":"published","year":"2017","publication_identifier":{"issn":["19466234"]},"date_created":"2018-12-11T11:47:48Z","doi":"10.1126/scitranslmed.aan2786","issue":"387","date_published":"2017-04-26T00:00:00Z","volume":9,"article_number":"2786","_id":"667","status":"public","type":"journal_article","user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","citation":{"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.","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","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.","short":"G. Novarino, Science Translational Medicine 9 (2017).","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.","ista":"Novarino G. 2017. The antisocial side of antibiotics. Science Translational Medicine. 9(387), 2786."},"date_updated":"2021-01-12T08:08:30Z","department":[{"_id":"GaNo"}],"title":"The antisocial side of antibiotics","publist_id":"7060","author":[{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","last_name":"Novarino"}]},{"article_number":"eaan8196","_id":"689","status":"public","type":"journal_article","user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","date_updated":"2021-01-12T08:09:29Z","citation":{"ista":"Novarino G. 2017. Rett syndrome modeling goes simian. Science Translational Medicine. 9(393), eaan8196.","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.","ieee":"G. Novarino, “Rett syndrome modeling goes simian,” Science Translational Medicine, vol. 9, no. 393. American Association for the Advancement of Science, 2017.","short":"G. Novarino, Science Translational Medicine 9 (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","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."},"title":"Rett syndrome modeling goes simian","department":[{"_id":"GaNo"}],"publist_id":"7019","author":[{"last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia"}],"oa_version":"None","abstract":[{"text":"Rett syndrome modeling in monkey mirrors the human disorder.","lang":"eng"}],"intvolume":" 9","month":"06","scopus_import":1,"quality_controlled":"1","publisher":"American Association for the Advancement of Science","publication":"Science Translational Medicine","language":[{"iso":"eng"}],"day":"07","publication_status":"published","year":"2017","publication_identifier":{"issn":["19466234"]},"date_created":"2018-12-11T11:47:56Z","date_published":"2017-06-07T00:00:00Z","volume":9,"doi":"10.1126/scitranslmed.aan8196","issue":"393"},{"quality_controlled":"1","publisher":"American Association for the Advancement of Science","scopus_import":1,"intvolume":" 9","month":"07","abstract":[{"text":"Leading autism-associated mutation in mouse partially mimics human disorder.\r\n\r\n","lang":"eng"}],"oa_version":"None","page":"eaao0972","date_created":"2018-12-11T11:48:01Z","issue":"399","date_published":"2017-07-19T00:00:00Z","volume":9,"doi":"10.1126/scitranslmed.aao0972","year":"2017","publication_status":"published","publication_identifier":{"issn":["19466234"]},"publication":"Science Translational Medicine","language":[{"iso":"eng"}],"day":"19","type":"journal_article","status":"public","_id":"702","publist_id":"6993","author":[{"last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia"}],"department":[{"_id":"GaNo"}],"title":"The riddle of CHD8 haploinsufficiency in autism spectrum disorder","date_updated":"2021-01-12T08:11:31Z","citation":{"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.","short":"G. Novarino, Science Translational Medicine 9 (2017) eaao0972.","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","ama":"Novarino G. The riddle of CHD8 haploinsufficiency in autism spectrum disorder. Science Translational Medicine. 2017;9(399):eaao0972. doi:10.1126/scitranslmed.aao0972","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.","ista":"Novarino G. 2017. The riddle of CHD8 haploinsufficiency in autism spectrum disorder. Science Translational Medicine. 9(399), eaao0972.","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."},"user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87"},{"date_updated":"2021-01-12T08:11:57Z","ddc":["576"],"department":[{"_id":"GaNo"},{"_id":"SiHi"}],"file_date_updated":"2020-07-14T12:47:50Z","_id":"713","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","pubrep_id":"885","status":"public","publication_status":"published","publication_identifier":{"issn":["2050084X"]},"language":[{"iso":"eng"}],"file":[{"file_name":"IST-2017-885-v1+1_elife-25125-figures-v2.pdf","date_created":"2018-12-12T10:13:36Z","file_size":6399510,"date_updated":"2020-07-14T12:47:50Z","creator":"system","file_id":"5020","checksum":"1ace3462e64a971b9ead896091829549","content_type":"application/pdf","relation":"main_file","access_level":"open_access"},{"date_updated":"2020-07-14T12:47:50Z","file_size":4264398,"creator":"system","date_created":"2018-12-12T10:13:36Z","file_name":"IST-2017-885-v1+2_elife-25125-v2.pdf","content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"6241dc31eeb87b03facadec3a53a6827","file_id":"5021"}],"volume":6,"abstract":[{"text":"To determine the dynamics of allelic-specific expression during mouse development, we analyzed RNA-seq data from 23 F1 tissues from different developmental stages, including 19 female tissues allowing X chromosome inactivation (XCI) escapers to also be detected. We demonstrate that allelic expression arising from genetic or epigenetic differences is highly tissue-specific. We find that tissue-specific strain-biased gene expression may be regulated by tissue-specific enhancers or by post-transcriptional differences in stability between the alleles. We also find that escape from X-inactivation is tissue-specific, with leg muscle showing an unexpectedly high rate of XCI escapers. By surveying a range of tissues during development, and performing extensive validation, we are able to provide a high confidence list of mouse imprinted genes including 18 novel genes. This shows that cluster size varies dynamically during development and can be substantially larger than previously thought, with the Igf2r cluster extending over 10 Mb in placenta.","lang":"eng"}],"oa_version":"Published Version","scopus_import":1,"intvolume":" 6","month":"08","citation":{"mla":"Andergassen, Daniel, et al. “Mapping the Mouse Allelome Reveals Tissue Specific Regulation of Allelic Expression.” ELife, vol. 6, e25125, eLife Sciences Publications, 2017, doi:10.7554/eLife.25125.","short":"D. Andergassen, C. Dotter, D. Wenzel, V. Sigl, P. Bammer, M. Muckenhuber, D. Mayer, T. Kulinski, H. Theussl, J. Penninger, C. Bock, D. Barlow, F. Pauler, Q. Hudson, ELife 6 (2017).","ieee":"D. Andergassen et al., “Mapping the mouse Allelome reveals tissue specific regulation of allelic expression,” eLife, vol. 6. eLife Sciences Publications, 2017.","ama":"Andergassen D, Dotter C, Wenzel D, et al. Mapping the mouse Allelome reveals tissue specific regulation of allelic expression. eLife. 2017;6. doi:10.7554/eLife.25125","apa":"Andergassen, D., Dotter, C., Wenzel, D., Sigl, V., Bammer, P., Muckenhuber, M., … Hudson, Q. (2017). Mapping the mouse Allelome reveals tissue specific regulation of allelic expression. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.25125","chicago":"Andergassen, Daniel, Christoph Dotter, Dyniel Wenzel, Verena Sigl, Philipp Bammer, Markus Muckenhuber, Daniela Mayer, et al. “Mapping the Mouse Allelome Reveals Tissue Specific Regulation of Allelic Expression.” ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.25125.","ista":"Andergassen D, Dotter C, Wenzel D, Sigl V, Bammer P, Muckenhuber M, Mayer D, Kulinski T, Theussl H, Penninger J, Bock C, Barlow D, Pauler F, Hudson Q. 2017. Mapping the mouse Allelome reveals tissue specific regulation of allelic expression. eLife. 6, e25125."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"first_name":"Daniel","last_name":"Andergassen","full_name":"Andergassen, Daniel"},{"first_name":"Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","full_name":"Dotter, Christoph","last_name":"Dotter"},{"first_name":"Dyniel","full_name":"Wenzel, Dyniel","last_name":"Wenzel"},{"first_name":"Verena","last_name":"Sigl","full_name":"Sigl, Verena"},{"first_name":"Philipp","last_name":"Bammer","full_name":"Bammer, Philipp"},{"full_name":"Muckenhuber, Markus","last_name":"Muckenhuber","first_name":"Markus"},{"full_name":"Mayer, Daniela","last_name":"Mayer","first_name":"Daniela"},{"last_name":"Kulinski","full_name":"Kulinski, Tomasz","first_name":"Tomasz"},{"full_name":"Theussl, Hans","last_name":"Theussl","first_name":"Hans"},{"full_name":"Penninger, Josef","last_name":"Penninger","first_name":"Josef"},{"first_name":"Christoph","full_name":"Bock, Christoph","last_name":"Bock"},{"first_name":"Denise","full_name":"Barlow, Denise","last_name":"Barlow"},{"id":"48EA0138-F248-11E8-B48F-1D18A9856A87","first_name":"Florian","full_name":"Pauler, Florian","last_name":"Pauler"},{"first_name":"Quanah","full_name":"Hudson, Quanah","last_name":"Hudson"}],"publist_id":"6971","title":"Mapping the mouse Allelome reveals tissue specific regulation of allelic expression","article_number":"e25125","project":[{"grant_number":"P27201-B22","name":"Revealing the mechanisms underlying drug interactions","call_identifier":"FWF","_id":"25E9AF9E-B435-11E9-9278-68D0E5697425"}],"year":"2017","has_accepted_license":"1","publication":"eLife","day":"14","date_created":"2018-12-11T11:48:05Z","date_published":"2017-08-14T00:00:00Z","doi":"10.7554/eLife.25125","oa":1,"publisher":"eLife Sciences Publications","quality_controlled":"1"},{"publication":"Drug and Alcohol Dependence","day":"01","year":"2017","date_created":"2018-12-11T11:48:05Z","doi":"10.1016/j.drugalcdep.2017.04.015","date_published":"2017-09-01T00:00:00Z","page":"7 - 14","acknowledgement":"This work was supported by the National Institutes of Health grants DA035926 (to MEA), and P30DA013429 (to EMU).","oa":1,"publisher":"Elsevier","quality_controlled":"1","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"mla":"Brailoiu, Gabriela, et al. “HIV Tat Excites D1 Receptor-like Expressing Neurons from Rat Nucleus Accumbens.” Drug and Alcohol Dependence, vol. 178, Elsevier, 2017, pp. 7–14, doi:10.1016/j.drugalcdep.2017.04.015.","ieee":"G. Brailoiu et al., “HIV Tat excites D1 receptor-like expressing neurons from rat nucleus accumbens,” Drug and Alcohol Dependence, vol. 178. Elsevier, pp. 7–14, 2017.","short":"G. Brailoiu, E. Deliu, J. Barr, L. Console Bram, A. Ciuciu, M. Abood, E. Unterwald, E. Brǎiloiu, Drug and Alcohol Dependence 178 (2017) 7–14.","apa":"Brailoiu, G., Deliu, E., Barr, J., Console Bram, L., Ciuciu, A., Abood, M., … Brǎiloiu, E. (2017). HIV Tat excites D1 receptor-like expressing neurons from rat nucleus accumbens. Drug and Alcohol Dependence. Elsevier. https://doi.org/10.1016/j.drugalcdep.2017.04.015","ama":"Brailoiu G, Deliu E, Barr J, et al. HIV Tat excites D1 receptor-like expressing neurons from rat nucleus accumbens. Drug and Alcohol Dependence. 2017;178:7-14. doi:10.1016/j.drugalcdep.2017.04.015","chicago":"Brailoiu, Gabriela, Elena Deliu, Jeffrey Barr, Linda Console Bram, Alexandra Ciuciu, Mary Abood, Ellen Unterwald, and Eugen Brǎiloiu. “HIV Tat Excites D1 Receptor-like Expressing Neurons from Rat Nucleus Accumbens.” Drug and Alcohol Dependence. Elsevier, 2017. https://doi.org/10.1016/j.drugalcdep.2017.04.015.","ista":"Brailoiu G, Deliu E, Barr J, Console Bram L, Ciuciu A, Abood M, Unterwald E, Brǎiloiu E. 2017. HIV Tat excites D1 receptor-like expressing neurons from rat nucleus accumbens. Drug and Alcohol Dependence. 178, 7–14."},"title":"HIV Tat excites D1 receptor-like expressing neurons from rat nucleus accumbens","external_id":{"pmid":["28623807"]},"article_processing_charge":"No","publist_id":"6967","author":[{"last_name":"Brailoiu","full_name":"Brailoiu, Gabriela","first_name":"Gabriela"},{"last_name":"Deliu","full_name":"Deliu, Elena","orcid":"0000-0002-7370-5293","first_name":"Elena","id":"37A40D7E-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Barr","full_name":"Barr, Jeffrey","first_name":"Jeffrey"},{"first_name":"Linda","last_name":"Console Bram","full_name":"Console Bram, Linda"},{"full_name":"Ciuciu, Alexandra","last_name":"Ciuciu","first_name":"Alexandra"},{"full_name":"Abood, Mary","last_name":"Abood","first_name":"Mary"},{"last_name":"Unterwald","full_name":"Unterwald, Ellen","first_name":"Ellen"},{"last_name":"Brǎiloiu","full_name":"Brǎiloiu, Eugen","first_name":"Eugen"}],"language":[{"iso":"eng"}],"publication_status":"published","publication_identifier":{"issn":["03768716"]},"volume":178,"pmid":1,"oa_version":"Submitted Version","abstract":[{"text":"Background HIV-1 infection and drug abuse are frequently co-morbid and their association greatly increases the severity of HIV-1-induced neuropathology. While nucleus accumbens (NAcc) function is severely perturbed by drugs of abuse, little is known about how HIV-1 infection affects NAcc. Methods We used calcium and voltage imaging to investigate the effect of HIV-1 trans-activator of transcription (Tat) on rat NAcc. Based on previous neuronal studies, we hypothesized that Tat modulates intracellular Ca2+ homeostasis of NAcc neurons. Results We provide evidence that Tat triggers a Ca2+ signaling cascade in NAcc medium spiny neurons (MSN) expressing D1-like dopamine receptors leading to neuronal depolarization. Firstly, Tat induced inositol 1,4,5-trisphsophate (IP3) receptor-mediated Ca2+ release from endoplasmic reticulum, followed by Ca2+ and Na+ influx via transient receptor potential canonical channels. The influx of cations depolarizes the membrane promoting additional Ca2+ entry through voltage-gated P/Q-type Ca2+ channels and opening of tetrodotoxin-sensitive Na+ channels. By activating this mechanism, Tat elicits a feed-forward depolarization increasing the excitability of D1-phosphatidylinositol-linked NAcc MSN. We previously found that cocaine targets NAcc neurons directly (independent of the inhibition of dopamine transporter) only when IP3-generating mechanisms are concomitantly initiated. When tested here, cocaine produced a dose-dependent potentiation of the effect of Tat on cytosolic Ca2+. Conclusion We describe for the first time a HIV-1 Tat-triggered Ca2+ signaling in MSN of NAcc involving TRPC and depolarization and a potentiation of the effect of Tat by cocaine, which may be relevant for the reward axis in cocaine-abusing HIV-1-positive patients.","lang":"eng"}],"intvolume":" 178","month":"09","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797705","open_access":"1"}],"scopus_import":1,"date_updated":"2021-01-12T08:12:00Z","department":[{"_id":"GaNo"}],"_id":"714","status":"public","article_type":"original","type":"journal_article"},{"type":"journal_article","status":"public","_id":"715","article_number":"aao4218","author":[{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"}],"publist_id":"6968","department":[{"_id":"GaNo"}],"title":"More excitation for Rett syndrome","date_updated":"2021-01-12T08:12:04Z","citation":{"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.","short":"G. Novarino, Science Translational Medicine 9 (2017).","ieee":"G. Novarino, “More excitation for Rett syndrome,” Science Translational Medicine, vol. 9, no. 405. American Association for the Advancement of Science, 2017.","ama":"Novarino G. More excitation for Rett syndrome. Science Translational Medicine. 2017;9(405). doi:10.1126/scitranslmed.aao4218","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","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.","ista":"Novarino G. 2017. More excitation for Rett syndrome. Science Translational Medicine. 9(405), aao4218."},"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","publisher":"American Association for the Advancement of Science","quality_controlled":"1","scopus_import":1,"month":"08","intvolume":" 9","abstract":[{"lang":"eng","text":"D-cycloserine ameliorates breathing abnormalities and survival rate in a mouse model of Rett syndrome."}],"oa_version":"None","issue":"405","volume":9,"doi":"10.1126/scitranslmed.aao4218","date_published":"2017-08-30T00:00:00Z","date_created":"2018-12-11T11:48:06Z","publication_identifier":{"issn":["19466234"]},"year":"2017","publication_status":"published","day":"30","language":[{"iso":"eng"}],"publication":"Science Translational Medicine"},{"date_updated":"2021-01-12T08:12:57Z","citation":{"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.","short":"G. Novarino, Science Translational Medicine 9 (2017).","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","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.","ista":"Novarino G. 2017. The science of love in ASD and ADHD. Science Translational Medicine. 9(411), eaap8168."},"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","author":[{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178"}],"publist_id":"6938","department":[{"_id":"GaNo"}],"title":"The science of love in ASD and ADHD","_id":"731","article_number":"eaap8168","type":"journal_article","status":"public","year":"2017","publication_status":"published","publication_identifier":{"issn":["19466234"]},"language":[{"iso":"eng"}],"publication":"Science Translational Medicine","day":"11","date_created":"2018-12-11T11:48:12Z","doi":"10.1126/scitranslmed.aap8168","issue":"411","volume":9,"date_published":"2017-10-11T00:00:00Z","abstract":[{"lang":"eng","text":"Genetic variations in the oxytocin receptor gene affect patients with ASD and ADHD differently."}],"oa_version":"None","publisher":"American Association for the Advancement of Science","quality_controlled":"1","scopus_import":1,"intvolume":" 9","month":"10"},{"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.","publisher":"Wiley-Blackwell","quality_controlled":"1","oa":1,"isi":1,"has_accepted_license":"1","year":"2017","day":"01","publication":"European Journal of Neuroscience","page":"45 - 57","date_published":"2017-01-01T00:00:00Z","doi":"10.1111/ejn.13418","date_created":"2018-12-11T11:50:50Z","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.","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","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","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.","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.","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.","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."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","publist_id":"6106","author":[{"first_name":"Ulrich","full_name":"Sauerzopf, Ulrich","last_name":"Sauerzopf"},{"last_name":"Sacco","full_name":"Sacco, Roberto","id":"42C9F57E-F248-11E8-B48F-1D18A9856A87","first_name":"Roberto"},{"last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Niello, Marco","last_name":"Niello","first_name":"Marco"},{"first_name":"Ana","last_name":"Weidenauer","full_name":"Weidenauer, Ana"},{"full_name":"Praschak Rieder, Nicole","last_name":"Praschak Rieder","first_name":"Nicole"},{"last_name":"Sitte","full_name":"Sitte, Harald","first_name":"Harald"},{"first_name":"Matthaeus","last_name":"Willeit","full_name":"Willeit, Matthaeus"}],"article_processing_charge":"No","external_id":{"isi":["000392487100005"],"pmid":["27690184"]},"title":"Are reprogrammed cells a useful tool for studying dopamine dysfunction in psychotic disorders? A review of the current evidence","abstract":[{"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.","lang":"eng"}],"oa_version":"Published Version","pmid":1,"scopus_import":"1","month":"01","intvolume":" 45","publication_status":"published","file":[{"content_type":"application/pdf","access_level":"open_access","relation":"main_file","checksum":"c572cf02be8fbb7020cfcfb892182e4c","file_id":"4838","date_updated":"2020-07-14T12:44:39Z","file_size":169145,"creator":"system","date_created":"2018-12-12T10:10:48Z","file_name":"IST-2017-738-v1+1_Sauerzopf_et_al-2017-European_Journal_of_Neuroscience.pdf"}],"language":[{"iso":"eng"}],"volume":45,"issue":"1","_id":"1228","type":"journal_article","article_type":"review","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","pubrep_id":"738","date_updated":"2023-09-20T11:16:01Z","ddc":["616"],"file_date_updated":"2020-07-14T12:44:39Z","department":[{"_id":"GaNo"}]},{"year":"2017","isi":1,"publication":"Neuroscience","day":"04","page":"23 - 32","date_created":"2018-12-11T11:48:17Z","date_published":"2017-12-04T00:00:00Z","doi":"10.1016/j.neuroscience.2017.09.034","oa":1,"quality_controlled":"1","publisher":"Elsevier","citation":{"mla":"Brǎiloiu, Eugen, et al. “Modulation of Cardiac Vagal Tone by Bradykinin Acting on Nucleus Ambiguus.” Neuroscience, vol. 365, Elsevier, 2017, pp. 23–32, doi:10.1016/j.neuroscience.2017.09.034.","apa":"Brǎiloiu, E., Mcguire, M., Shuler, S., Deliu, E., Barr, J., Abood, M., & Brailoiu, G. (2017). Modulation of cardiac vagal tone by bradykinin acting on nucleus ambiguus. Neuroscience. Elsevier. https://doi.org/10.1016/j.neuroscience.2017.09.034","ama":"Brǎiloiu E, Mcguire M, Shuler S, et al. Modulation of cardiac vagal tone by bradykinin acting on nucleus ambiguus. Neuroscience. 2017;365:23-32. doi:10.1016/j.neuroscience.2017.09.034","short":"E. Brǎiloiu, M. Mcguire, S. Shuler, E. Deliu, J. Barr, M. Abood, G. Brailoiu, Neuroscience 365 (2017) 23–32.","ieee":"E. Brǎiloiu et al., “Modulation of cardiac vagal tone by bradykinin acting on nucleus ambiguus,” Neuroscience, vol. 365. Elsevier, pp. 23–32, 2017.","chicago":"Brǎiloiu, Eugen, Matthew Mcguire, Shadaria Shuler, Elena Deliu, Jeffrey Barr, Mary Abood, and Gabriela Brailoiu. “Modulation of Cardiac Vagal Tone by Bradykinin Acting on Nucleus Ambiguus.” Neuroscience. Elsevier, 2017. https://doi.org/10.1016/j.neuroscience.2017.09.034.","ista":"Brǎiloiu E, Mcguire M, Shuler S, Deliu E, Barr J, Abood M, Brailoiu G. 2017. Modulation of cardiac vagal tone by bradykinin acting on nucleus ambiguus. Neuroscience. 365, 23–32."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","external_id":{"pmid":["28951324"],"isi":["000415966200003"]},"article_processing_charge":"No","author":[{"last_name":"Brǎiloiu","full_name":"Brǎiloiu, Eugen","first_name":"Eugen"},{"full_name":"Mcguire, Matthew","last_name":"Mcguire","first_name":"Matthew"},{"first_name":"Shadaria","full_name":"Shuler, Shadaria","last_name":"Shuler"},{"first_name":"Elena","id":"37A40D7E-F248-11E8-B48F-1D18A9856A87","full_name":"Deliu, Elena","orcid":"0000-0002-7370-5293","last_name":"Deliu"},{"first_name":"Jeffrey","full_name":"Barr, Jeffrey","last_name":"Barr"},{"full_name":"Abood, Mary","last_name":"Abood","first_name":"Mary"},{"last_name":"Brailoiu","full_name":"Brailoiu, Gabriela","first_name":"Gabriela"}],"publist_id":"6911","title":"Modulation of cardiac vagal tone by bradykinin acting on nucleus ambiguus","publication_status":"published","publication_identifier":{"issn":["03064522"]},"language":[{"iso":"eng"}],"volume":365,"abstract":[{"lang":"eng","text":"Bradykinin (BK), a component of the kallikrein-kininogen-kinin system exerts multiple effects via B1 and B2 receptor activation. In the cardiovascular system, bradykinin has cardioprotective and vasodilator properties. We investigated the effect of BK on cardiac-projecting neurons of nucleus ambiguus, a key site for the parasympathetic cardiac regulation. BK produced a dose-dependent increase in cytosolic Ca2+ concentration. Pretreatment with HOE140, a B2 receptor antagonist, but not with R715, a B1 receptor antagonist, abolished the response to BK. A selective B2 receptor agonist, but not a B1 receptor agonist, elicited an increase in cytosolic Ca2+ similarly to BK. Inhibition of N-type voltage-gated Ca2+ channels with ω-conotoxin GVIA had no effect on the Ca2+ signal produced by BK, while pretreatment with ω-conotoxin MVIIC, a blocker of P/Q-type of Ca2+ channels, significantly diminished the effect of BK. Pretreatment with xestospongin C and 2-aminoethoxydiphenyl borate, antagonists of inositol 1,4,5-trisphosphate receptors, abolished the response to BK. Inhibition of ryanodine receptors reduced the BK-induced Ca2+ increase, while disruption of lysosomal Ca2+ stores with bafilomycin A1 did not affect the response. BK produced a dose-dependent depolarization of nucleus ambiguus neurons, which was prevented by the B2 receptor antagonist. In vivo studies indicate that microinjection of BK into nucleus ambiguus elicited bradycardia in conscious rats via B2 receptors. In summary, in cardiac vagal neurons of nucleus ambiguus, BK activates B2 receptors promoting Ca2+ influx and Ca2+ release from endoplasmic reticulum, and membrane depolarization; these effects are translated in vivo by bradycardia."}],"pmid":1,"oa_version":"Submitted Version","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5798458","open_access":"1"}],"scopus_import":"1","intvolume":" 365","month":"12","date_updated":"2023-09-27T12:26:59Z","department":[{"_id":"GaNo"}],"_id":"747","type":"journal_article","article_type":"original","status":"public"},{"ddc":["576"],"date_updated":"2021-01-12T06:49:20Z","department":[{"_id":"GaNo"}],"file_date_updated":"2020-07-14T12:44:41Z","_id":"1240","status":"public","pubrep_id":"709","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"file":[{"file_id":"4789","checksum":"a268beee1a690801c83ec6729f9ebc5b","content_type":"application/pdf","access_level":"open_access","relation":"main_file","date_created":"2018-12-12T10:10:05Z","file_name":"IST-2016-709-v1+1_s13059-016-0873-8.pdf","date_updated":"2020-07-14T12:44:41Z","file_size":2914601,"creator":"system"}],"language":[{"iso":"eng"}],"publication_status":"published","issue":"1","volume":17,"oa_version":"Published Version","abstract":[{"lang":"eng","text":"Background: Long non-coding RNAs (lncRNAs) are increasingly implicated as gene regulators and may ultimately be more numerous than protein-coding genes in the human genome. Despite large numbers of reported lncRNAs, reference annotations are likely incomplete due to their lower and tighter tissue-specific expression compared to mRNAs. An unexplored factor potentially confounding lncRNA identification is inter-individual expression variability. Here, we characterize lncRNA natural expression variability in human primary granulocytes. Results: We annotate granulocyte lncRNAs and mRNAs in RNA-seq data from 10 healthy individuals, identifying multiple lncRNAs absent from reference annotations, and use this to investigate three known features (higher tissue-specificity, lower expression, and reduced splicing efficiency) of lncRNAs relative to mRNAs. Expression variability was examined in seven individuals sampled three times at 1- or more than 1-month intervals. We show that lncRNAs display significantly more inter-individual expression variability compared to mRNAs. We confirm this finding in two independent human datasets by analyzing multiple tissues from the GTEx project and lymphoblastoid cell lines from the GEUVADIS project. Using the latter dataset we also show that including more human donors into the transcriptome annotation pipeline allows identification of an increasing number of lncRNAs, but minimally affects mRNA gene number. Conclusions: A comprehensive annotation of lncRNAs is known to require an approach that is sensitive to low and tight tissue-specific expression. Here we show that increased inter-individual expression variability is an additional general lncRNA feature to consider when creating a comprehensive annotation of human lncRNAs or proposing their use as prognostic or disease markers."}],"month":"01","intvolume":" 17","scopus_import":1,"user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","citation":{"apa":"Kornienko, A., Dotter, C., Guenzl, P., Gisslinger, H., Gisslinger, B., Cleary, C., … Barlow, D. (2016). Long non-coding RNAs display higher natural expression variation than protein-coding genes in healthy humans. Genome Biology. BioMed Central. https://doi.org/10.1186/s13059-016-0873-8","ama":"Kornienko A, Dotter C, Guenzl P, et al. Long non-coding RNAs display higher natural expression variation than protein-coding genes in healthy humans. Genome Biology. 2016;17(1). doi:10.1186/s13059-016-0873-8","short":"A. Kornienko, C. Dotter, P. Guenzl, H. Gisslinger, B. Gisslinger, C. Cleary, R. Kralovics, F. Pauler, D. Barlow, Genome Biology 17 (2016).","ieee":"A. Kornienko et al., “Long non-coding RNAs display higher natural expression variation than protein-coding genes in healthy humans,” Genome Biology, vol. 17, no. 1. BioMed Central, 2016.","mla":"Kornienko, Aleksandra, et al. “Long Non-Coding RNAs Display Higher Natural Expression Variation than Protein-Coding Genes in Healthy Humans.” Genome Biology, vol. 17, no. 1, 14, BioMed Central, 2016, doi:10.1186/s13059-016-0873-8.","ista":"Kornienko A, Dotter C, Guenzl P, Gisslinger H, Gisslinger B, Cleary C, Kralovics R, Pauler F, Barlow D. 2016. Long non-coding RNAs display higher natural expression variation than protein-coding genes in healthy humans. Genome Biology. 17(1), 14.","chicago":"Kornienko, Aleksandra, Christoph Dotter, Philipp Guenzl, Heinz Gisslinger, Bettina Gisslinger, Ciara Cleary, Robert Kralovics, Florian Pauler, and Denise Barlow. “Long Non-Coding RNAs Display Higher Natural Expression Variation than Protein-Coding Genes in Healthy Humans.” Genome Biology. BioMed Central, 2016. https://doi.org/10.1186/s13059-016-0873-8."},"title":"Long non-coding RNAs display higher natural expression variation than protein-coding genes in healthy humans","author":[{"first_name":"Aleksandra","last_name":"Kornienko","full_name":"Kornienko, Aleksandra"},{"first_name":"Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","full_name":"Dotter, Christoph","last_name":"Dotter"},{"last_name":"Guenzl","full_name":"Guenzl, Philipp","first_name":"Philipp"},{"first_name":"Heinz","last_name":"Gisslinger","full_name":"Gisslinger, Heinz"},{"first_name":"Bettina","full_name":"Gisslinger, Bettina","last_name":"Gisslinger"},{"first_name":"Ciara","full_name":"Cleary, Ciara","last_name":"Cleary"},{"first_name":"Robert","full_name":"Kralovics, Robert","last_name":"Kralovics"},{"id":"48EA0138-F248-11E8-B48F-1D18A9856A87","first_name":"Florian","last_name":"Pauler","full_name":"Pauler, Florian"},{"last_name":"Barlow","full_name":"Barlow, Denise","first_name":"Denise"}],"publist_id":"6093","article_number":"14","day":"29","publication":"Genome Biology","has_accepted_license":"1","year":"2016","date_published":"2016-01-29T00:00:00Z","doi":"10.1186/s13059-016-0873-8","date_created":"2018-12-11T11:50:53Z","acknowledgement":"This study was partly funded by the Austrian Science Fund (FWF F43-B09, FWF W1207-B09). PMG is a recipient of a DOC Fellowship of the Austrian Academy of Sciences.\r\nWe thank Ruth Klement, Tomasz Kulinski, Elisangela Valente, Elisabeth Salzer,\r\nand Roland Jäger for technical/bioinformatic assistance and advice, the CeMM\r\nIT department and José Manuel Molero for help and advice on software usage,\r\nthe Biomedical Sequencing Facility (http://biomedical-sequencing.at/) for\r\nsequencing and advice, Jacques Colinge, Daniel Andergassen, and Tomasz\r\nKulinski for discussions, Quanah Hudson and Jörg Menche for reading and\r\ncommenting on the manuscript.","quality_controlled":"1","publisher":"BioMed Central","oa":1},{"publist_id":"6170","author":[{"first_name":"Dora-Clara","id":"2ABCE612-F248-11E8-B48F-1D18A9856A87","last_name":"Tarlungeanu","full_name":"Tarlungeanu, Dora-Clara"},{"last_name":"Deliu","full_name":"Deliu, Elena","orcid":"0000-0002-7370-5293","id":"37A40D7E-F248-11E8-B48F-1D18A9856A87","first_name":"Elena"},{"orcid":"0000-0002-9033-9096","full_name":"Dotter, Christoph","last_name":"Dotter","first_name":"Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Kara","full_name":"Kara, Majdi","first_name":"Majdi"},{"first_name":"Philipp","last_name":"Janiesch","full_name":"Janiesch, Philipp"},{"first_name":"Mariafrancesca","last_name":"Scalise","full_name":"Scalise, Mariafrancesca"},{"full_name":"Galluccio, Michele","last_name":"Galluccio","first_name":"Michele"},{"first_name":"Mateja","last_name":"Tesulov","full_name":"Tesulov, Mateja"},{"id":"3F4D1282-F248-11E8-B48F-1D18A9856A87","first_name":"Emanuela","last_name":"Morelli","full_name":"Morelli, Emanuela"},{"full_name":"Sönmez, Fatma","last_name":"Sönmez","first_name":"Fatma"},{"first_name":"Kaya","last_name":"Bilgüvar","full_name":"Bilgüvar, Kaya"},{"full_name":"Ohgaki, Ryuichi","last_name":"Ohgaki","first_name":"Ryuichi"},{"last_name":"Kanai","full_name":"Kanai, Yoshikatsu","first_name":"Yoshikatsu"},{"last_name":"Johansen","full_name":"Johansen, Anide","first_name":"Anide"},{"last_name":"Esharif","full_name":"Esharif, Seham","first_name":"Seham"},{"first_name":"Tawfeg","last_name":"Ben Omran","full_name":"Ben Omran, Tawfeg"},{"first_name":"Meral","full_name":"Topcu, Meral","last_name":"Topcu"},{"full_name":"Schlessinger, Avner","last_name":"Schlessinger","first_name":"Avner"},{"last_name":"Indiveri","full_name":"Indiveri, Cesare","first_name":"Cesare"},{"first_name":"Kent","full_name":"Duncan, Kent","last_name":"Duncan"},{"first_name":"Ahmet","last_name":"Caglayan","full_name":"Caglayan, Ahmet"},{"first_name":"Murat","last_name":"Günel","full_name":"Günel, Murat"},{"full_name":"Gleeson, Joseph","last_name":"Gleeson","first_name":"Joseph"},{"last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"}],"article_processing_charge":"No","title":"Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder","citation":{"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.","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.","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","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","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.","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.","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."},"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","project":[{"call_identifier":"FWF","_id":"25473368-B435-11E9-9278-68D0E5697425","name":"Transmembrane Transporters in Health and Disease","grant_number":"F03523"}],"page":"1481 - 1494","doi":"10.1016/j.cell.2016.11.013","date_published":"2016-12-01T00:00:00Z","date_created":"2018-12-11T11:50:35Z","has_accepted_license":"1","year":"2016","day":"01","publication":"Cell","quality_controlled":"1","publisher":"Cell Press","oa":1,"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","file_date_updated":"2020-07-14T12:44:37Z","department":[{"_id":"GaNo"}],"date_updated":"2024-03-27T23:30:12Z","ddc":["576","616"],"type":"journal_article","article_type":"original","status":"public","pubrep_id":"771","_id":"1183","volume":167,"related_material":{"record":[{"id":"395","status":"public","relation":"dissertation_contains"}]},"issue":"6","publication_status":"published","file":[{"content_type":"application/pdf","access_level":"open_access","relation":"main_file","file_id":"5030","checksum":"7fe01ab12a6610d3db421e0136db2f77","date_updated":"2020-07-14T12:44:37Z","file_size":73907957,"creator":"system","date_created":"2018-12-12T10:13:44Z","file_name":"IST-2017-771-v1+1_Tarlungeanu_et_al._Final_edited.pdf"}],"language":[{"iso":"eng"}],"scopus_import":"1","month":"12","intvolume":" 167","abstract":[{"lang":"eng","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."}],"oa_version":"Submitted Version"},{"oa_version":"Published Version","abstract":[{"lang":"eng","text":"Detecting allelic biases from high-throughput sequencing data requires an approach that maximises sensitivity while minimizing false positives. Here, we present Allelome.PRO, an automated user-friendly bioinformatics pipeline, which uses high-throughput sequencing data from reciprocal crosses of two genetically distinct mouse strains to detect allele-specific expression and chromatin modifications. Allelome.PRO extends approaches used in previous studies that exclusively analyzed imprinted expression to give a complete picture of the ‘allelome’ by automatically categorising the allelic expression of all genes in a given cell type into imprinted, strain-biased, biallelic or non-informative. Allelome.PRO offers increased sensitivity to analyze lowly expressed transcripts, together with a robust false discovery rate empirically calculated from variation in the sequencing data. We used RNA-seq data from mouse embryonic fibroblasts from F1 reciprocal crosses to determine a biologically relevant allelic ratio cutoff, and define for the first time an entire allelome. Furthermore, we show that Allelome.PRO detects differential enrichment of H3K4me3 over promoters from ChIP-seq data validating the RNA-seq results. This approach can be easily extended to analyze histone marks of active enhancers, or transcription factor binding sites and therefore provides a powerful tool to identify candidate cis regulatory elements genome wide."}],"intvolume":" 43","month":"07","scopus_import":1,"language":[{"iso":"eng"}],"file":[{"file_name":"2015_NucleicAcidsRes_Andergassen.pdf","date_created":"2018-12-20T14:18:57Z","creator":"dernst","file_size":6863297,"date_updated":"2020-07-14T12:44:58Z","file_id":"5768","checksum":"385b83854fd0eb2e4f386867da2823e2","relation":"main_file","access_level":"open_access","content_type":"application/pdf"}],"publication_status":"published","issue":"21","volume":43,"_id":"1497","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","ddc":["570"],"date_updated":"2021-01-12T06:51:09Z","department":[{"_id":"GaNo"}],"file_date_updated":"2020-07-14T12:44:58Z","acknowledgement":"Austrian Science Fund [FWF P25185-B22, FWF F4302- B09, FWFW1207-B09]. Funding for open access charge: Austrian Science Fund.\r\nWe thank Florian Breitwieser for advice during the early stages of this project. High-throughput sequencing was conducted by the Biomedical Sequencing Facility (BSF) at CeMM in Vienna.","oa":1,"quality_controlled":"1","publisher":"Oxford University Press","publication":"Nucleic Acids Research","day":"21","year":"2015","has_accepted_license":"1","date_created":"2018-12-11T11:52:22Z","doi":"10.1093/nar/gkv727","date_published":"2015-07-21T00:00:00Z","article_number":"e146","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"mla":"Andergassen, Daniel, et al. “Allelome.PRO, a Pipeline to Define Allele-Specific Genomic Features from High-Throughput Sequencing Data.” Nucleic Acids Research, vol. 43, no. 21, e146, Oxford University Press, 2015, doi:10.1093/nar/gkv727.","ieee":"D. Andergassen et al., “Allelome.PRO, a pipeline to define allele-specific genomic features from high-throughput sequencing data,” Nucleic Acids Research, vol. 43, no. 21. Oxford University Press, 2015.","short":"D. Andergassen, C. Dotter, T. Kulinski, P. Guenzl, P. Bammer, D. Barlow, F. Pauler, Q. Hudson, Nucleic Acids Research 43 (2015).","apa":"Andergassen, D., Dotter, C., Kulinski, T., Guenzl, P., Bammer, P., Barlow, D., … Hudson, Q. (2015). Allelome.PRO, a pipeline to define allele-specific genomic features from high-throughput sequencing data. Nucleic Acids Research. Oxford University Press. https://doi.org/10.1093/nar/gkv727","ama":"Andergassen D, Dotter C, Kulinski T, et al. Allelome.PRO, a pipeline to define allele-specific genomic features from high-throughput sequencing data. Nucleic Acids Research. 2015;43(21). doi:10.1093/nar/gkv727","chicago":"Andergassen, Daniel, Christoph Dotter, Tomasz Kulinski, Philipp Guenzl, Philipp Bammer, Denise Barlow, Florian Pauler, and Quanah Hudson. “Allelome.PRO, a Pipeline to Define Allele-Specific Genomic Features from High-Throughput Sequencing Data.” Nucleic Acids Research. Oxford University Press, 2015. https://doi.org/10.1093/nar/gkv727.","ista":"Andergassen D, Dotter C, Kulinski T, Guenzl P, Bammer P, Barlow D, Pauler F, Hudson Q. 2015. Allelome.PRO, a pipeline to define allele-specific genomic features from high-throughput sequencing data. Nucleic Acids Research. 43(21), e146."},"title":"Allelome.PRO, a pipeline to define allele-specific genomic features from high-throughput sequencing data","publist_id":"5682","author":[{"first_name":"Daniel","full_name":"Andergassen, Daniel","last_name":"Andergassen"},{"full_name":"Dotter, Christoph","last_name":"Dotter","first_name":"Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Tomasz","last_name":"Kulinski","full_name":"Kulinski, Tomasz"},{"full_name":"Guenzl, Philipp","last_name":"Guenzl","first_name":"Philipp"},{"first_name":"Philipp","last_name":"Bammer","full_name":"Bammer, Philipp"},{"first_name":"Denise","full_name":"Barlow, Denise","last_name":"Barlow"},{"last_name":"Pauler","full_name":"Pauler, Florian","first_name":"Florian"},{"full_name":"Hudson, Quanah","last_name":"Hudson","first_name":"Quanah"}]},{"oa_version":"Submitted Version","pmid":1,"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."}],"intvolume":" 23","month":"06","main_file_link":[{"url":"http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4795044/","open_access":"1"}],"language":[{"iso":"eng"}],"publication_status":"published","issue":"6","volume":23,"_id":"1789","status":"public","type":"journal_article","date_updated":"2021-01-12T06:53:12Z","department":[{"_id":"GaNo"}],"oa":1,"quality_controlled":"1","publisher":"Nature Publishing Group","publication":"European Journal of Human Genetics","day":"15","year":"2015","date_created":"2018-12-11T11:54:01Z","date_published":"2015-06-15T00:00:00Z","doi":"10.1038/ejhg.2014.165","page":"753 - 760","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"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.","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.","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","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","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.","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."},"title":"Loss-of-function variants of SETD5 cause intellectual disability and the core phenotype of microdeletion 3p25.3 syndrome","external_id":{"pmid":["25138099"]},"publist_id":"5324","author":[{"first_name":"Alma","last_name":"Kuechler","full_name":"Kuechler, Alma"},{"last_name":"Zink","full_name":"Zink, Alexander","first_name":"Alexander"},{"last_name":"Wieland","full_name":"Wieland, Thomas","first_name":"Thomas"},{"last_name":"Lüdecke","full_name":"Lüdecke, Hermann","first_name":"Hermann"},{"last_name":"Cremer","full_name":"Cremer, Kirsten","first_name":"Kirsten"},{"full_name":"Salviati, Leonardo","last_name":"Salviati","first_name":"Leonardo"},{"full_name":"Magini, Pamela","last_name":"Magini","first_name":"Pamela"},{"first_name":"Kimia","last_name":"Najafi","full_name":"Najafi, Kimia"},{"last_name":"Zweier","full_name":"Zweier, Christiane","first_name":"Christiane"},{"first_name":"Johanna","last_name":"Czeschik","full_name":"Czeschik, Johanna"},{"last_name":"Aretz","full_name":"Aretz, Stefan","first_name":"Stefan"},{"full_name":"Endele, Sabine","last_name":"Endele","first_name":"Sabine"},{"full_name":"Tamburrino, Federica","last_name":"Tamburrino","first_name":"Federica"},{"first_name":"Claudia","last_name":"Pinato","full_name":"Pinato, Claudia"},{"last_name":"Clementi","full_name":"Clementi, Maurizio","first_name":"Maurizio"},{"first_name":"Jasmin","full_name":"Gundlach, Jasmin","last_name":"Gundlach"},{"first_name":"Carina","last_name":"Maylahn","full_name":"Maylahn, Carina"},{"first_name":"Laura","last_name":"Mazzanti","full_name":"Mazzanti, Laura"},{"full_name":"Wohlleber, Eva","last_name":"Wohlleber","first_name":"Eva"},{"last_name":"Schwarzmayr","full_name":"Schwarzmayr, Thomas","first_name":"Thomas"},{"first_name":"Roxana","full_name":"Kariminejad, Roxana","last_name":"Kariminejad"},{"first_name":"Avner","last_name":"Schlessinger","full_name":"Schlessinger, Avner"},{"last_name":"Wieczorek","full_name":"Wieczorek, Dagmar","first_name":"Dagmar"},{"first_name":"Tim","full_name":"Strom, Tim","last_name":"Strom"},{"last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Engels","full_name":"Engels, Hartmut","first_name":"Hartmut"}]},{"publication_status":"published","language":[{"iso":"eng"}],"volume":343,"issue":"6170","abstract":[{"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.","lang":"eng"}],"pmid":1,"oa_version":"Submitted Version","main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157572/"}],"scopus_import":1,"intvolume":" 343","month":"01","date_updated":"2021-01-12T06:54:03Z","department":[{"_id":"GaNo"}],"_id":"1916","article_type":"original","type":"journal_article","status":"public","year":"2014","publication":"Science","day":"31","page":"506 - 511","date_created":"2018-12-11T11:54:42Z","doi":"10.1126/science.1247363","date_published":"2014-01-31T00:00:00Z","acknowledgement":"Supported by the Deutsche Forschungsgemeinschaft (G.N.)","oa":1,"publisher":"American Association for the Advancement of Science","quality_controlled":"1","citation":{"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.","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.","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","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","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.","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.","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."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","external_id":{"pmid":["24482476"]},"article_processing_charge":"No","author":[{"orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia"},{"full_name":"Fenstermaker, Ali","last_name":"Fenstermaker","first_name":"Ali"},{"last_name":"Zaki","full_name":"Zaki, Maha","first_name":"Maha"},{"first_name":"Matan","last_name":"Hofree","full_name":"Hofree, Matan"},{"full_name":"Silhavy, Jennifer","last_name":"Silhavy","first_name":"Jennifer"},{"last_name":"Heiberg","full_name":"Heiberg, Andrew","first_name":"Andrew"},{"last_name":"Abdellateef","full_name":"Abdellateef, Mostafa","first_name":"Mostafa"},{"last_name":"Rosti","full_name":"Rosti, Başak","first_name":"Başak"},{"first_name":"Eric","last_name":"Scott","full_name":"Scott, Eric"},{"full_name":"Mansour, Lobna","last_name":"Mansour","first_name":"Lobna"},{"first_name":"Amira","last_name":"Masri","full_name":"Masri, Amira"},{"last_name":"Kayserili","full_name":"Kayserili, Hülya","first_name":"Hülya"},{"full_name":"Al Aama, Jumana","last_name":"Al Aama","first_name":"Jumana"},{"first_name":"Ghada","full_name":"Abdel Salam, Ghada","last_name":"Abdel Salam"},{"last_name":"Karminejad","full_name":"Karminejad, Ariana","first_name":"Ariana"},{"last_name":"Kara","full_name":"Kara, Majdi","first_name":"Majdi"},{"first_name":"Bülent","full_name":"Kara, Bülent","last_name":"Kara"},{"first_name":"Bita","full_name":"Bozorgmehri, Bita","last_name":"Bozorgmehri"},{"first_name":"Tawfeg","full_name":"Ben Omran, Tawfeg","last_name":"Ben Omran"},{"first_name":"Faezeh","full_name":"Mojahedi, Faezeh","last_name":"Mojahedi"},{"full_name":"Mahmoud, Iman","last_name":"Mahmoud","first_name":"Iman"},{"last_name":"Bouslam","full_name":"Bouslam, Naïma","first_name":"Naïma"},{"last_name":"Bouhouche","full_name":"Bouhouche, Ahmed","first_name":"Ahmed"},{"last_name":"Benomar","full_name":"Benomar, Ali","first_name":"Ali"},{"last_name":"Hanein","full_name":"Hanein, Sylvain","first_name":"Sylvain"},{"first_name":"Laure","full_name":"Raymond, Laure","last_name":"Raymond"},{"first_name":"Sylvie","full_name":"Forlani, Sylvie","last_name":"Forlani"},{"full_name":"Mascaro, Massimo","last_name":"Mascaro","first_name":"Massimo"},{"last_name":"Selim","full_name":"Selim, Laila","first_name":"Laila"},{"first_name":"Nabil","full_name":"Shehata, Nabil","last_name":"Shehata"},{"last_name":"Al Allawi","full_name":"Al Allawi, Nasir","first_name":"Nasir"},{"first_name":"Parayil","last_name":"Bindu","full_name":"Bindu, Parayil"},{"first_name":"Matloob","full_name":"Azam, Matloob","last_name":"Azam"},{"last_name":"Günel","full_name":"Günel, Murat","first_name":"Murat"},{"full_name":"Caglayan, Ahmet","last_name":"Caglayan","first_name":"Ahmet"},{"first_name":"Kaya","full_name":"Bilgüvar, Kaya","last_name":"Bilgüvar"},{"full_name":"Tolun, Aslihan","last_name":"Tolun","first_name":"Aslihan"},{"last_name":"Issa","full_name":"Issa, Mahmoud","first_name":"Mahmoud"},{"first_name":"Jana","full_name":"Schroth, Jana","last_name":"Schroth"},{"first_name":"Emily","full_name":"Spencer, Emily","last_name":"Spencer"},{"first_name":"Rasim","last_name":"Rosti","full_name":"Rosti, Rasim"},{"last_name":"Akizu","full_name":"Akizu, Naiara","first_name":"Naiara"},{"first_name":"Keith","full_name":"Vaux, Keith","last_name":"Vaux"},{"first_name":"Anide","full_name":"Johansen, Anide","last_name":"Johansen"},{"full_name":"Koh, Alice","last_name":"Koh","first_name":"Alice"},{"first_name":"Hisham","full_name":"Megahed, Hisham","last_name":"Megahed"},{"last_name":"Dürr","full_name":"Dürr, Alexandra","first_name":"Alexandra"},{"last_name":"Brice","full_name":"Brice, Alexis","first_name":"Alexis"},{"last_name":"Stévanin","full_name":"Stévanin, Giovanni","first_name":"Giovanni"},{"first_name":"Stacy","full_name":"Gabriel, Stacy","last_name":"Gabriel"},{"last_name":"Ideker","full_name":"Ideker, Trey","first_name":"Trey"},{"first_name":"Joseph","last_name":"Gleeson","full_name":"Gleeson, Joseph"}],"publist_id":"5178","title":"Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders"}]