[{"type":"preprint","project":[{"grant_number":"FTI21-D-046","name":"Entwicklung und Funktion der V1 Interneuronen vom Schwimmen zum Laufen während der Metamorphose von Xenopus","_id":"bd73af52-d553-11ed-ba76-912049f0ac7a"},{"name":"Development and Evolution of Tetrapod Motor Circuits","grant_number":"101041551","_id":"ebb66355-77a9-11ec-83b8-b8ac210a4dae"}],"status":"public","_id":"15016","author":[{"full_name":"Jaeger, Eliza C.B.","last_name":"Jaeger","first_name":"Eliza C.B."},{"id":"cf391e77-ec3c-11ea-a124-d69323410b58","first_name":"David","full_name":"Vijatovic, David","last_name":"Vijatovic"},{"last_name":"Deryckere","full_name":"Deryckere, Astrid","first_name":"Astrid"},{"first_name":"Nikol","full_name":"Zorin, Nikol","last_name":"Zorin"},{"last_name":"Nguyen","full_name":"Nguyen, Akemi L.","first_name":"Akemi L."},{"id":"eaf2b366-cfd1-11ee-bbdf-c8790f800a05","first_name":"Georgiy","last_name":"Ivanian","full_name":"Ivanian, Georgiy"},{"first_name":"Jamie","last_name":"Woych","full_name":"Woych, Jamie"},{"last_name":"Arnold","full_name":"Arnold, Rebecca C","first_name":"Rebecca C","id":"d6cce458-14c9-11ed-a755-c1c8fc6fde6f"},{"first_name":"Alonso","last_name":"Ortega Gurrola","full_name":"Ortega Gurrola, Alonso"},{"last_name":"Shvartsman","full_name":"Shvartsman, Arik","first_name":"Arik"},{"last_name":"Barbieri","full_name":"Barbieri, Francesca","id":"a9492887-8972-11ed-ae7b-bfae10998254","first_name":"Francesca"},{"full_name":"Toma, Florina-Alexandra","last_name":"Toma","id":"85dd99f2-15b2-11ec-abd3-d1ae4d57f3b5","first_name":"Florina-Alexandra"},{"last_name":"Gorbsky","full_name":"Gorbsky, Gary J.","first_name":"Gary J."},{"first_name":"Marko E.","last_name":"Horb","full_name":"Horb, Marko E."},{"first_name":"Hollis T.","last_name":"Cline","full_name":"Cline, Hollis T."},{"last_name":"Shay","full_name":"Shay, Timothy F.","first_name":"Timothy F."},{"first_name":"Darcy B.","last_name":"Kelley","full_name":"Kelley, Darcy B."},{"last_name":"Yamaguchi","full_name":"Yamaguchi, Ayako","first_name":"Ayako"},{"full_name":"Shein-Idelson, Mark","last_name":"Shein-Idelson","first_name":"Mark"},{"first_name":"Maria Antonietta","last_name":"Tosches","full_name":"Tosches, Maria Antonietta"},{"last_name":"Sweeney","full_name":"Sweeney, Lora Beatrice Jaeger","orcid":"0000-0001-9242-5601","first_name":"Lora Beatrice Jaeger","id":"56BE8254-C4F0-11E9-8E45-0B23E6697425"}],"article_processing_charge":"No","title":"Adeno-associated viral tools to trace neural development and connectivity across amphibians","department":[{"_id":"LoSw"},{"_id":"MaDe"},{"_id":"GaNo"}],"citation":{"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.","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. .","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","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"},"date_updated":"2024-02-20T09:34:25Z","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","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"}],"oa_version":"Preprint","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).","doi":"10.1101/2024.02.15.580289","date_published":"2024-02-16T00:00:00Z","date_created":"2024-02-20T09:20:32Z","publication_status":"submitted","year":"2024","day":"16","publication":"bioRxiv","language":[{"iso":"eng"}]},{"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"}],"oa_version":"None","pmid":1,"scopus_import":"1","month":"10","intvolume":" 80","publication_identifier":{"eissn":["2168-6238"]},"publication_status":"published","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","day":"01","publication":"JAMA Psychiatry","page":"1066-1074","doi":"10.1001/jamapsychiatry.2023.2996","date_published":"2023-10-01T00:00:00Z","date_created":"2023-10-22T22:01:14Z","citation":{"ista":"Schumann G, Andreassen OA, Banaschewski T, Calhoun VD, Clinton N, Desrivieres S, Brandlistuen RE, Feng J, Hese S, Hitchen E, Hoffmann P, Jia T, Jirsa V, Marquand AF, Nees F, Nöthen MM, Novarino G, Polemiti E, Ralser M, Rapp M, Schepanski K, Schikowski T, Slater M, Sommer P, Stahl BC, Thompson PM, Twardziok S, Van Der Meer D, Walter H, Westlye L. 2023. Addressing global environmental challenges to mental health using population neuroscience: A review. JAMA Psychiatry. 80(10), 1066–1074.","chicago":"Schumann, Gunter, Ole A. Andreassen, Tobias Banaschewski, Vince D. Calhoun, Nicholas Clinton, Sylvane Desrivieres, Ragnhild Eek Brandlistuen, et al. “Addressing Global Environmental Challenges to Mental Health Using Population Neuroscience: A Review.” JAMA Psychiatry. American Medical Association, 2023. https://doi.org/10.1001/jamapsychiatry.2023.2996.","ama":"Schumann G, Andreassen OA, Banaschewski T, et al. Addressing global environmental challenges to mental health using population neuroscience: A review. JAMA Psychiatry. 2023;80(10):1066-1074. doi:10.1001/jamapsychiatry.2023.2996","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.","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."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"full_name":"Schumann, Gunter","last_name":"Schumann","first_name":"Gunter"},{"first_name":"Ole A.","full_name":"Andreassen, Ole A.","last_name":"Andreassen"},{"first_name":"Tobias","full_name":"Banaschewski, Tobias","last_name":"Banaschewski"},{"first_name":"Vince D.","full_name":"Calhoun, Vince D.","last_name":"Calhoun"},{"last_name":"Clinton","full_name":"Clinton, Nicholas","first_name":"Nicholas"},{"first_name":"Sylvane","last_name":"Desrivieres","full_name":"Desrivieres, 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","last_name":"Hitchen","full_name":"Hitchen, Esther"},{"last_name":"Hoffmann","full_name":"Hoffmann, Per","first_name":"Per"},{"first_name":"Tianye","full_name":"Jia, Tianye","last_name":"Jia"},{"first_name":"Viktor","full_name":"Jirsa, Viktor","last_name":"Jirsa"},{"full_name":"Marquand, Andre F.","last_name":"Marquand","first_name":"Andre F."},{"first_name":"Frauke","full_name":"Nees, Frauke","last_name":"Nees"},{"first_name":"Markus M.","last_name":"Nöthen","full_name":"Nöthen, Markus M."},{"last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Elli","last_name":"Polemiti","full_name":"Polemiti, Elli"},{"first_name":"Markus","full_name":"Ralser, Markus","last_name":"Ralser"},{"first_name":"Michael","last_name":"Rapp","full_name":"Rapp, Michael"},{"first_name":"Kerstin","last_name":"Schepanski","full_name":"Schepanski, Kerstin"},{"first_name":"Tamara","last_name":"Schikowski","full_name":"Schikowski, Tamara"},{"first_name":"Mel","full_name":"Slater, Mel","last_name":"Slater"},{"first_name":"Peter","last_name":"Sommer","full_name":"Sommer, Peter"},{"first_name":"Bernd Carsten","last_name":"Stahl","full_name":"Stahl, Bernd Carsten"},{"first_name":"Paul M.","full_name":"Thompson, Paul M.","last_name":"Thompson"},{"first_name":"Sven","last_name":"Twardziok","full_name":"Twardziok, Sven"},{"last_name":"Van Der Meer","full_name":"Van Der Meer, Dennis","first_name":"Dennis"},{"first_name":"Henrik","full_name":"Walter, Henrik","last_name":"Walter"},{"full_name":"Westlye, Lars","last_name":"Westlye","first_name":"Lars"}],"external_id":{"pmid":["37610741"]},"article_processing_charge":"No","title":"Addressing global environmental challenges to mental health using population neuroscience: A review"},{"article_processing_charge":"No","external_id":{"isi":["001013172700001"]},"author":[{"last_name":"Xu","full_name":"Xu, Jiayuan","first_name":"Jiayuan"},{"last_name":"Liu","full_name":"Liu, Nana","first_name":"Nana"},{"first_name":"Elli","last_name":"Polemiti","full_name":"Polemiti, Elli"},{"full_name":"Garcia-Mondragon, Liliana","last_name":"Garcia-Mondragon","first_name":"Liliana"},{"full_name":"Tang, Jie","last_name":"Tang","first_name":"Jie"},{"first_name":"Xiaoxuan","full_name":"Liu, Xiaoxuan","last_name":"Liu"},{"last_name":"Lett","full_name":"Lett, Tristram","first_name":"Tristram"},{"full_name":"Yu, Le","last_name":"Yu","first_name":"Le"},{"full_name":"Nöthen, Markus M.","last_name":"Nöthen","first_name":"Markus M."},{"first_name":"Jianfeng","last_name":"Feng","full_name":"Feng, Jianfeng"},{"last_name":"Yu","full_name":"Yu, Chunshui","first_name":"Chunshui"},{"first_name":"Andre","full_name":"Marquand, Andre","last_name":"Marquand"},{"first_name":"Gunter","last_name":"Schumann","full_name":"Schumann, Gunter"},{"full_name":"Walter, Henrik","last_name":"Walter","first_name":"Henrik"},{"first_name":"Andreas","last_name":"Heinz","full_name":"Heinz, Andreas"},{"first_name":"Markus","full_name":"Ralser, Markus","last_name":"Ralser"},{"full_name":"Twardziok, Sven","last_name":"Twardziok","first_name":"Sven"},{"last_name":"Vaidya","full_name":"Vaidya, Nilakshi","first_name":"Nilakshi"},{"first_name":"Emin","full_name":"Serin, Emin","last_name":"Serin"},{"first_name":"Marcel","last_name":"Jentsch","full_name":"Jentsch, Marcel"},{"full_name":"Hitchen, Esther","last_name":"Hitchen","first_name":"Esther"},{"first_name":"Roland","last_name":"Eils","full_name":"Eils, Roland"},{"first_name":"Ulrike Helene","last_name":"Taron","full_name":"Taron, Ulrike Helene"},{"first_name":"Tatjana","last_name":"Schütz","full_name":"Schütz, Tatjana"},{"full_name":"Schepanski, Kerstin","last_name":"Schepanski","first_name":"Kerstin"},{"first_name":"Jamie","last_name":"Banks","full_name":"Banks, Jamie"},{"first_name":"Tobias","last_name":"Banaschewski","full_name":"Banaschewski, Tobias"},{"first_name":"Karina","last_name":"Jansone","full_name":"Jansone, Karina"},{"first_name":"Nina","full_name":"Christmann, Nina","last_name":"Christmann"},{"first_name":"Andreas","full_name":"Meyer-Lindenberg, Andreas","last_name":"Meyer-Lindenberg"},{"last_name":"Tost","full_name":"Tost, Heike","first_name":"Heike"},{"first_name":"Nathalie","full_name":"Holz, Nathalie","last_name":"Holz"},{"last_name":"Schwarz","full_name":"Schwarz, Emanuel","first_name":"Emanuel"},{"full_name":"Stringaris, Argyris","last_name":"Stringaris","first_name":"Argyris"},{"full_name":"Neidhart, Maja","last_name":"Neidhart","first_name":"Maja"},{"full_name":"Nees, Frauke","last_name":"Nees","first_name":"Frauke"},{"last_name":"Siehl","full_name":"Siehl, Sebastian","first_name":"Sebastian"},{"first_name":"Ole","last_name":"A. Andreassen","full_name":"A. Andreassen, Ole"},{"first_name":"Lars","full_name":"T. Westlye, Lars","last_name":"T. Westlye"},{"first_name":"Dennis","full_name":"Van Der Meer, Dennis","last_name":"Van Der Meer"},{"first_name":"Sara","full_name":"Fernandez, Sara","last_name":"Fernandez"},{"full_name":"Kjelkenes, Rikka","last_name":"Kjelkenes","first_name":"Rikka"},{"last_name":"Ask","full_name":"Ask, Helga","first_name":"Helga"},{"first_name":"Michael","last_name":"Rapp","full_name":"Rapp, Michael"},{"first_name":"Mira","last_name":"Tschorn","full_name":"Tschorn, Mira"},{"last_name":"Böttger","full_name":"Böttger, Sarah Jane","first_name":"Sarah Jane"},{"last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Marr","full_name":"Marr, Lena","first_name":"Lena","id":"4406F586-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Mel","last_name":"Slater","full_name":"Slater, Mel"},{"first_name":"Guillem Feixas","full_name":"Viapiana, Guillem Feixas","last_name":"Viapiana"},{"first_name":"Francisco Eiroa","full_name":"Orosa, Francisco Eiroa","last_name":"Orosa"},{"last_name":"Gallego","full_name":"Gallego, Jaime","first_name":"Jaime"},{"full_name":"Pastor, Alvaro","last_name":"Pastor","first_name":"Alvaro"},{"last_name":"Forstner","full_name":"Forstner, Andreas","first_name":"Andreas"},{"first_name":"Per","last_name":"Hoffmann","full_name":"Hoffmann, Per"},{"first_name":"Markus","last_name":"M. Nöthen","full_name":"M. Nöthen, Markus"},{"first_name":"Andreas","last_name":"J. Forstner","full_name":"J. Forstner, Andreas"},{"last_name":"Claus","full_name":"Claus, Isabelle","first_name":"Isabelle"},{"first_name":"Abbi","last_name":"Miller","full_name":"Miller, Abbi"},{"full_name":"Heilmann-Heimbach, Stefanie","last_name":"Heilmann-Heimbach","first_name":"Stefanie"},{"last_name":"Sommer","full_name":"Sommer, Peter","first_name":"Peter"},{"first_name":"Mona","last_name":"Boye","full_name":"Boye, Mona"},{"full_name":"Wilbertz, Johannes","last_name":"Wilbertz","first_name":"Johannes"},{"first_name":"Karen","last_name":"Schmitt","full_name":"Schmitt, Karen"},{"first_name":"Viktor","last_name":"Jirsa","full_name":"Jirsa, Viktor"},{"full_name":"Petkoski, Spase","last_name":"Petkoski","first_name":"Spase"},{"full_name":"Pitel, Séverine","last_name":"Pitel","first_name":"Séverine"},{"first_name":"Lisa","full_name":"Otten, Lisa","last_name":"Otten"},{"first_name":"Anastasios Polykarpos","full_name":"Athanasiadis, Anastasios Polykarpos","last_name":"Athanasiadis"},{"full_name":"Pearmund, Charlie","last_name":"Pearmund","first_name":"Charlie"},{"full_name":"Spanlang, Bernhard","last_name":"Spanlang","first_name":"Bernhard"},{"first_name":"Elena","full_name":"Alvarez, Elena","last_name":"Alvarez"},{"first_name":"Mavi","full_name":"Sanchez, Mavi","last_name":"Sanchez"},{"first_name":"Arantxa","full_name":"Giner, Arantxa","last_name":"Giner"},{"last_name":"Hese","full_name":"Hese, Sören","first_name":"Sören"},{"full_name":"Renner, Paul","last_name":"Renner","first_name":"Paul"},{"full_name":"Jia, Tianye","last_name":"Jia","first_name":"Tianye"},{"first_name":"Yanting","full_name":"Gong, Yanting","last_name":"Gong"},{"full_name":"Xia, Yunman","last_name":"Xia","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","last_name":"Liu","full_name":"Liu, Jingyu"},{"full_name":"Thompson, Paul","last_name":"Thompson","first_name":"Paul"},{"last_name":"Clinton","full_name":"Clinton, Nicholas","first_name":"Nicholas"},{"first_name":"Sylvane","last_name":"Desrivieres","full_name":"Desrivieres, Sylvane"},{"full_name":"H. Young, Allan","last_name":"H. Young","first_name":"Allan"},{"first_name":"Bernd","full_name":"Stahl, Bernd","last_name":"Stahl"},{"last_name":"Ogoh","full_name":"Ogoh, George","first_name":"George"}],"title":"Effects of urban living environments on mental health in adults","citation":{"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.","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","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","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.","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.","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."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","oa":1,"publisher":"Springer Nature","quality_controlled":"1","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.","page":"1456-1467","date_created":"2023-06-25T22:00:46Z","doi":"10.1038/s41591-023-02365-w","date_published":"2023-06-15T00:00:00Z","year":"2023","isi":1,"has_accepted_license":"1","publication":"Nature Medicine","day":"15","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","status":"public","_id":"13168","department":[{"_id":"GaNo"}],"file_date_updated":"2023-06-26T10:15:44Z","date_updated":"2023-12-13T11:25:55Z","ddc":["570"],"scopus_import":"1","intvolume":" 29","month":"06","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."}],"oa_version":"Published Version","license":"https://creativecommons.org/licenses/by/4.0/","volume":29,"publication_status":"published","publication_identifier":{"eissn":["1546-170X"],"issn":["1078-8956"]},"language":[{"iso":"eng"}],"file":[{"file_id":"13171","checksum":"bcd3225b2731c3442fa98987fd3bd46d","success":1,"access_level":"open_access","relation":"main_file","content_type":"application/pdf","date_created":"2023-06-26T10:15:44Z","file_name":"2023_NatureMedicine_Xu.pdf","creator":"dernst","date_updated":"2023-06-26T10:15:44Z","file_size":7365360}]},{"scopus_import":"1","intvolume":" 14","month":"10","pmid":1,"oa_version":"Published Version","volume":14,"publication_status":"published","publication_identifier":{"eissn":["1664-0640"]},"language":[{"iso":"eng"}],"file":[{"content_type":"application/pdf","relation":"main_file","access_level":"open_access","success":1,"checksum":"0a76373e9a4c0fc199f80380de257e86","file_id":"14468","file_size":147878,"date_updated":"2023-10-30T12:48:40Z","creator":"dernst","file_name":"2023_FrontiersPsychiatry_Narzisi.pdf","date_created":"2023-10-30T12:48:40Z"}],"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":"letter_note","type":"journal_article","status":"public","_id":"14455","department":[{"_id":"GaNo"}],"file_date_updated":"2023-10-30T12:48:40Z","date_updated":"2023-12-13T13:06:07Z","ddc":["570"],"oa":1,"publisher":"Frontiers","quality_controlled":"1","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.","date_created":"2023-10-29T23:01:16Z","doi":"10.3389/fpsyt.2023.1287879","date_published":"2023-10-03T00:00:00Z","year":"2023","isi":1,"has_accepted_license":"1","publication":"Frontiers in Psychiatry","day":"03","article_number":"1287879","external_id":{"isi":["001084841700001"],"pmid":["37854442"]},"article_processing_charge":"Yes","author":[{"full_name":"Narzisi, Antonio","last_name":"Narzisi","first_name":"Antonio"},{"last_name":"Halladay","full_name":"Halladay, Alycia","first_name":"Alycia"},{"last_name":"Masi","full_name":"Masi, Gabriele","first_name":"Gabriele"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178"},{"first_name":"Catherine","full_name":"Lord, Catherine","last_name":"Lord"}],"title":"Tempering expectations: Considerations on the current state of stem cells therapy for autism treatment","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.","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.","short":"A. Narzisi, A. Halladay, G. Masi, G. Novarino, C. Lord, Frontiers in Psychiatry 14 (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"},{"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","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.).","title":"Dense 4D nanoscale reconstruction of living brain tissue","author":[{"id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","first_name":"Philipp","last_name":"Velicky","orcid":"0000-0002-2340-7431","full_name":"Velicky, Philipp"},{"first_name":"Eder","id":"3FB91342-F248-11E8-B48F-1D18A9856A87","last_name":"Miguel Villalba","orcid":"0000-0001-5665-0430","full_name":"Miguel Villalba, Eder"},{"last_name":"Michalska","orcid":"0000-0003-3862-1235","full_name":"Michalska, Julia M","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","first_name":"Julia M"},{"first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","last_name":"Lyudchik","full_name":"Lyudchik, Julia"},{"full_name":"Wei, Donglai","last_name":"Wei","first_name":"Donglai"},{"last_name":"Lin","full_name":"Lin, Zudi","first_name":"Zudi"},{"last_name":"Watson","full_name":"Watson, Jake","orcid":"0000-0002-8698-3823","id":"63836096-4690-11EA-BD4E-32803DDC885E","first_name":"Jake"},{"first_name":"Jakob","full_name":"Troidl, Jakob","last_name":"Troidl"},{"full_name":"Beyer, Johanna","last_name":"Beyer","first_name":"Johanna"},{"id":"43DF3136-F248-11E8-B48F-1D18A9856A87","first_name":"Yoav","last_name":"Ben Simon","full_name":"Ben Simon, Yoav"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M","last_name":"Sommer","full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105"},{"full_name":"Jahr, Wiebke","last_name":"Jahr","first_name":"Wiebke","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87"},{"id":"9ac8f577-2357-11eb-997a-e566c5550886","first_name":"Alban","full_name":"Cenameri, Alban","last_name":"Cenameri"},{"full_name":"Broichhagen, Johannes","last_name":"Broichhagen","first_name":"Johannes"},{"first_name":"Seth G.N.","last_name":"Grant","full_name":"Grant, Seth G.N."},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","first_name":"Peter M","full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas"},{"orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","last_name":"Novarino","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Pfister","full_name":"Pfister, Hanspeter","first_name":"Hanspeter"},{"full_name":"Bickel, Bernd","orcid":"0000-0001-6511-9385","last_name":"Bickel","first_name":"Bernd","id":"49876194-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Danzl","orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G","first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87"}],"article_processing_charge":"Yes","external_id":{"pmid":["37429995"],"isi":["001025621500001"]},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"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.","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","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.","ieee":"P. Velicky et al., “Dense 4D nanoscale reconstruction of living brain tissue,” Nature Methods, vol. 20. Springer Nature, pp. 1256–1265, 2023."},"project":[{"name":"Optical control of synaptic function via adhesion molecules","grant_number":"I03600","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"name":"Molecular Drug Targets","grant_number":"W1232-B24","_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF"},{"call_identifier":"FWF","_id":"25C5A090-B435-11E9-9278-68D0E5697425","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","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"grant_number":"715767","name":"MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and Modeling","call_identifier":"H2020","_id":"24F9549A-B435-11E9-9278-68D0E5697425"},{"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"},{"call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425","grant_number":"692692","name":"Biophysics and circuit function of a giant cortical glumatergic synapse"},{"call_identifier":"H2020","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","grant_number":"101026635","name":"Synaptic computations of the hippocampal CA3 circuitry"},{"grant_number":"LT00057","name":"High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration","_id":"2668BFA0-B435-11E9-9278-68D0E5697425"}],"volume":20,"related_material":{"link":[{"url":"https://github.com/danzllab/LIONESS","relation":"software"}],"record":[{"status":"public","id":"12817","relation":"research_data"},{"id":"14770","status":"public","relation":"shorter_version"}]},"ec_funded":1,"language":[{"iso":"eng"}],"publication_identifier":{"eissn":["1548-7105"],"issn":["1548-7091"]},"publication_status":"published","month":"08","intvolume":" 20","scopus_import":"1","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1038/s41592-023-01936-6"}],"pmid":1,"oa_version":"Published Version","acknowledged_ssus":[{"_id":"ScienComp"},{"_id":"Bio"},{"_id":"PreCl"},{"_id":"E-Lib"},{"_id":"LifeSc"},{"_id":"M-Shop"}],"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."}],"department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"},{"_id":"Bio"}],"date_updated":"2024-01-10T08:37:48Z","status":"public","type":"journal_article","article_type":"original","_id":"13267"},{"_id":"13107","type":"dissertation","status":"public","date_updated":"2024-02-07T08:03:33Z","supervisor":[{"last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"}],"ddc":["570"],"file_date_updated":"2023-06-07T08:41:49Z","department":[{"_id":"GradSch"},{"_id":"GaNo"}],"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"Bio"},{"_id":"EM-Fac"}],"abstract":[{"lang":"eng","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."}],"oa_version":"Published Version","alternative_title":["ISTA Thesis"],"month":"05","publication_status":"published","degree_awarded":"PhD","publication_identifier":{"issn":["2663 - 337X"]},"language":[{"iso":"eng"}],"file":[{"checksum":"4b69a4ac0bbf4163d59c0b58dcb4f2c3","file_id":"13112","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","access_level":"closed","relation":"source_file","date_created":"2023-06-01T13:48:41Z","file_name":"Thesis_Lisa Knaus_approved_final.docx","date_updated":"2023-06-01T13:48:41Z","file_size":12991551,"creator":"lknaus"},{"content_type":"application/pdf","access_level":"open_access","relation":"main_file","file_id":"13114","checksum":"6903d152aa01181d87a696085af31c83","date_updated":"2023-06-07T08:41:49Z","file_size":9309015,"creator":"lknaus","date_created":"2023-06-02T09:47:29Z","file_name":"Thesis_Lisa Knaus_approved_final_pdfa2b.pdf"}],"ec_funded":1,"related_material":{"record":[{"id":"12802","status":"public","relation":"part_of_dissertation"}]},"project":[{"_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models"},{"name":"Molecular Drug Targets","grant_number":"W1232-B24","call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425"}],"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.","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.","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","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"},"user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","article_processing_charge":"No","author":[{"first_name":"Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","full_name":"Knaus, Lisa","last_name":"Knaus"}],"title":"The metabolism of the developing brain : How large neutral amino acids modulate perinatal neuronal excitability and survival","oa":1,"publisher":"Institute of Science and Technology Austria","year":"2023","has_accepted_license":"1","day":"31","page":"147","date_created":"2023-06-01T09:05:24Z","doi":"10.15479/at:ista:13107","date_published":"2023-05-31T00:00:00Z"},{"project":[{"grant_number":"W1232-B24","name":"Molecular Drug Targets","call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425"},{"name":"Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development","grant_number":"725780","_id":"260018B0-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models"}],"external_id":{"isi":["000991468700001"]},"article_processing_charge":"Yes (via OA deal)","author":[{"last_name":"Knaus","full_name":"Knaus, Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","first_name":"Lisa"},{"last_name":"Basilico","full_name":"Basilico, Bernadette","orcid":"0000-0003-1843-3173","first_name":"Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425"},{"last_name":"Malzl","full_name":"Malzl, Daniel","first_name":"Daniel"},{"first_name":"Maria","full_name":"Gerykova Bujalkova, Maria","last_name":"Gerykova Bujalkova"},{"full_name":"Smogavec, Mateja","last_name":"Smogavec","first_name":"Mateja"},{"last_name":"Schwarz","full_name":"Schwarz, Lena A.","first_name":"Lena A."},{"first_name":"Sarah","id":"f141a35d-15a9-11ec-9fb2-fef6becc7b6f","full_name":"Gorkiewicz, Sarah","last_name":"Gorkiewicz"},{"last_name":"Amberg","full_name":"Amberg, Nicole","orcid":"0000-0002-3183-8207","id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","first_name":"Nicole"},{"first_name":"Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","full_name":"Pauler, Florian","orcid":"0000-0002-7462-0048","last_name":"Pauler"},{"last_name":"Knittl-Frank","full_name":"Knittl-Frank, Christian","first_name":"Christian"},{"full_name":"Tassinari, Marianna","last_name":"Tassinari","first_name":"Marianna","id":"7af593f1-d44a-11ed-bf94-a3646a6bb35e"},{"first_name":"Nuno","full_name":"Maulide, Nuno","last_name":"Maulide"},{"last_name":"Rülicke","full_name":"Rülicke, Thomas","first_name":"Thomas"},{"full_name":"Menche, Jörg","last_name":"Menche","first_name":"Jörg"},{"orcid":"0000-0003-2279-1061","full_name":"Hippenmeyer, Simon","last_name":"Hippenmeyer","first_name":"Simon","id":"37B36620-F248-11E8-B48F-1D18A9856A87"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178"}],"title":"Large neutral amino acid levels tune perinatal neuronal excitability and survival","citation":{"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","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.","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.","ista":"Knaus L, Basilico B, Malzl D, Gerykova Bujalkova M, Smogavec M, Schwarz LA, Gorkiewicz S, Amberg N, Pauler F, Knittl-Frank C, Tassinari M, Maulide N, Rülicke T, Menche J, Hippenmeyer S, Novarino G. 2023. Large neutral amino acid levels tune perinatal neuronal excitability and survival. Cell. 186(9), 1950–1967.e25.","chicago":"Knaus, Lisa, Bernadette Basilico, Daniel Malzl, Maria Gerykova Bujalkova, Mateja Smogavec, Lena A. Schwarz, Sarah Gorkiewicz, et al. “Large Neutral Amino Acid Levels Tune Perinatal Neuronal Excitability and Survival.” Cell. Elsevier, 2023. https://doi.org/10.1016/j.cell.2023.02.037."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa":1,"quality_controlled":"1","publisher":"Elsevier","acknowledgement":"We thank A. Freeman and V. Voronin for technical assistance, S. Deixler, A. Stichelberger, M. Schunn, and the Preclinical Facility for managing our animal colony. We thank L. Andersen and J. Sonntag, who were involved in generating the MADM lines. We thank the ISTA LSF Mass Spectrometry Core Facility for assistance with the proteomic analysis, as well as the ISTA electron microscopy and Imaging and Optics facility for technical support. Metabolomics LC-MS/MS analysis was performed by the Metabolomics Facility at Vienna BioCenter Core Facilities (VBCF). We acknowledge the support of the EMBL Metabolomics Core Facility (MCF) for lipidomics and intracellular metabolomics mass spectrometry data acquisition and analysis. RNA sequencing was performed by the Next Generation Sequencing Facility at VBCF. Schematics were generated using Biorender.com. This work was supported by the Austrian Science Fund (FWF, DK W1232-B24) and by the European Union’s Horizon 2020 research and innovation program (ERC) grant 725780 (LinPro) to S.H. and 715508 (REVERSEAUTISM) to G.N.","page":"1950-1967.e25","date_created":"2023-04-05T08:15:40Z","doi":"10.1016/j.cell.2023.02.037","date_published":"2023-04-27T00:00:00Z","year":"2023","has_accepted_license":"1","isi":1,"publication":"Cell","day":"27","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","_id":"12802","department":[{"_id":"SiHi"},{"_id":"GaNo"}],"file_date_updated":"2023-05-02T09:26:21Z","date_updated":"2024-02-07T08:03:32Z","ddc":["570"],"scopus_import":"1","intvolume":" 186","month":"04","abstract":[{"lang":"eng","text":"Little is known about the critical metabolic changes that neural cells have to undergo during development and how temporary shifts in this program can influence brain circuitries and behavior. Inspired by the discovery that mutations in SLC7A5, a transporter of metabolically essential large neutral amino acids (LNAAs), lead to autism, we employed metabolomic profiling to study the metabolic states of the cerebral cortex across different developmental stages. We found that the forebrain undergoes significant metabolic remodeling throughout development, with certain groups of metabolites showing stage-specific changes, but what are the consequences of perturbing this metabolic program? By manipulating Slc7a5 expression in neural cells, we found that the metabolism of LNAAs and lipids are interconnected in the cortex. Deletion of Slc7a5 in neurons affects the postnatal metabolic state, leading to a shift in lipid metabolism. Additionally, it causes stage- and cell-type-specific alterations in neuronal activity patterns, resulting in a long-term circuit dysfunction."}],"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"EM-Fac"},{"_id":"Bio"},{"_id":"LifeSc"}],"oa_version":"Published Version","ec_funded":1,"issue":"9","volume":186,"related_material":{"link":[{"url":"https://ista.ac.at/en/news/feed-them-or-lose-them/","relation":"press_release","description":"News on ISTA Website"}],"record":[{"relation":"dissertation_contains","status":"public","id":"13107"}]},"publication_status":"published","publication_identifier":{"issn":["0092-8674"]},"language":[{"iso":"eng"}],"file":[{"date_created":"2023-05-02T09:26:21Z","file_name":"2023_Cell_Knaus.pdf","date_updated":"2023-05-02T09:26:21Z","file_size":15712841,"creator":"dernst","file_id":"12889","checksum":"47e94fbe19e86505b429cb7a5b503ce6","success":1,"content_type":"application/pdf","access_level":"open_access","relation":"main_file"}]},{"date_updated":"2024-02-21T12:18:18Z","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"},{"_id":"Bio"},{"_id":"RySh"}],"_id":"14257","status":"public","type":"journal_article","article_type":"original","language":[{"iso":"eng"}],"publication_identifier":{"eissn":["1546-1696"],"issn":["1087-0156"]},"publication_status":"epub_ahead","related_material":{"link":[{"relation":"software","url":"https://github.com/danzllab/CATS"}],"record":[{"relation":"research_data","status":"public","id":"13126"}]},"ec_funded":1,"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"}],"month":"08","scopus_import":"1","main_file_link":[{"url":"https://doi.org/10.1038/s41587-023-01911-8","open_access":"1"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","citation":{"ista":"Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer CM, Amberg N, Venturino A, Roessler K, Czech T, Höftberger R, Siegert S, Novarino G, Jonas PM, Danzl JG. 2023. Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology.","chicago":"Michalska, Julia M, Julia Lyudchik, Philipp Velicky, Hana Korinkova, Jake Watson, Alban Cenameri, Christoph M Sommer, et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” Nature Biotechnology. Springer Nature, 2023. 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","apa":"Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri, A., … Danzl, J. G. (2023). Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology. Springer Nature. https://doi.org/10.1038/s41587-023-01911-8","ieee":"J. M. Michalska et al., “Imaging brain tissue architecture across millimeter to nanometer scales,” Nature Biotechnology. Springer Nature, 2023.","short":"J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri, C.M. Sommer, N. Amberg, A. Venturino, K. Roessler, T. Czech, R. Höftberger, S. Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, Nature Biotechnology (2023).","mla":"Michalska, Julia M., et al. “Imaging Brain Tissue Architecture across Millimeter to Nanometer Scales.” Nature Biotechnology, Springer Nature, 2023, doi:10.1038/s41587-023-01911-8."},"title":"Imaging brain tissue architecture across millimeter to nanometer scales","author":[{"full_name":"Michalska, Julia M","orcid":"0000-0003-3862-1235","last_name":"Michalska","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","first_name":"Julia M"},{"full_name":"Lyudchik, Julia","last_name":"Lyudchik","id":"46E28B80-F248-11E8-B48F-1D18A9856A87","first_name":"Julia"},{"id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","first_name":"Philipp","last_name":"Velicky","full_name":"Velicky, Philipp","orcid":"0000-0002-2340-7431"},{"full_name":"Korinkova, Hana","last_name":"Korinkova","first_name":"Hana","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed"},{"full_name":"Watson, Jake","orcid":"0000-0002-8698-3823","last_name":"Watson","first_name":"Jake","id":"63836096-4690-11EA-BD4E-32803DDC885E"},{"first_name":"Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886","full_name":"Cenameri, Alban","last_name":"Cenameri"},{"first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","last_name":"Sommer","full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105"},{"id":"4CD6AAC6-F248-11E8-B48F-1D18A9856A87","first_name":"Nicole","last_name":"Amberg","orcid":"0000-0002-3183-8207","full_name":"Amberg, Nicole"},{"last_name":"Venturino","orcid":"0000-0003-2356-9403","full_name":"Venturino, Alessandro","id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","first_name":"Alessandro"},{"first_name":"Karl","full_name":"Roessler, Karl","last_name":"Roessler"},{"first_name":"Thomas","last_name":"Czech","full_name":"Czech, Thomas"},{"first_name":"Romana","last_name":"Höftberger","full_name":"Höftberger, Romana"},{"last_name":"Siegert","full_name":"Siegert, Sandra","orcid":"0000-0001-8635-0877","first_name":"Sandra","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino"},{"full_name":"Jonas, Peter M","orcid":"0000-0001-5001-4804","last_name":"Jonas","first_name":"Peter M","id":"353C1B58-F248-11E8-B48F-1D18A9856A87"},{"id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G","orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G","last_name":"Danzl"}],"article_processing_charge":"Yes (in subscription journal)","external_id":{"isi":["001065254200001"]},"project":[{"call_identifier":"FWF","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","name":"Optical control of synaptic function via adhesion molecules","grant_number":"I03600"},{"grant_number":"W1232-B24","name":"Molecular Drug Targets","call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425"},{"_id":"25C5A090-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","grant_number":"Z00312","name":"The Wittgenstein Prize"},{"name":"High content imaging to decode human immune cell interactions in health and allergic disease","_id":"23889792-32DE-11EA-91FC-C7463DDC885E"},{"grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425"},{"name":"Biophysics and circuit function of a giant cortical glumatergic synapse","grant_number":"692692","call_identifier":"H2020","_id":"25B7EB9E-B435-11E9-9278-68D0E5697425"},{"name":"International IST Doctoral Program","grant_number":"665385","_id":"2564DBCA-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"call_identifier":"H2020","_id":"fc2be41b-9c52-11eb-aca3-faa90aa144e9","grant_number":"101026635","name":"Synaptic computations of the hippocampal CA3 circuitry"}],"day":"31","publication":"Nature Biotechnology","isi":1,"year":"2023","date_published":"2023-08-31T00:00:00Z","doi":"10.1038/s41587-023-01911-8","date_created":"2023-09-03T22:01:15Z","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.).","publisher":"Springer Nature","quality_controlled":"1","oa":1},{"date_created":"2023-01-12T12:04:50Z","date_published":"2022-11-04T00:00:00Z","doi":"10.3389/fncel.2022.1022431","publication":"Frontiers in Cellular Neuroscience","day":"04","year":"2022","isi":1,"has_accepted_license":"1","oa":1,"publisher":"Frontiers Media","quality_controlled":"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).","title":"What microglia depletion approaches tell us about the role of microglia on synaptic function and behavior","external_id":{"pmid":["36406752"],"isi":["000886526600001"]},"article_processing_charge":"No","author":[{"last_name":"Basilico","orcid":"0000-0003-1843-3173","full_name":"Basilico, Bernadette","first_name":"Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425"},{"first_name":"Laura","last_name":"Ferrucci","full_name":"Ferrucci, Laura"},{"full_name":"Khan, Azka","last_name":"Khan","first_name":"Azka"},{"last_name":"Di Angelantonio","full_name":"Di Angelantonio, Silvia","first_name":"Silvia"},{"last_name":"Ragozzino","full_name":"Ragozzino, Davide","first_name":"Davide"},{"last_name":"Reverte","full_name":"Reverte, Ingrid","first_name":"Ingrid"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"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.","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.","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.","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).","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","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"},"article_number":"1022431","volume":16,"language":[{"iso":"eng"}],"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}],"publication_status":"published","publication_identifier":{"issn":["1662-5102"]},"intvolume":" 16","month":"11","scopus_import":"1","pmid":1,"oa_version":"Published Version","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"}],"department":[{"_id":"GaNo"}],"file_date_updated":"2023-01-24T09:16:29Z","ddc":["570"],"date_updated":"2023-08-04T08:56:10Z","keyword":["Cellular and Molecular Neuroscience"],"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","_id":"12140"},{"ec_funded":1,"volume":145,"issue":"8","publication_status":"published","publication_identifier":{"issn":["0006-8950"],"eissn":["1460-2156"]},"language":[{"iso":"eng"}],"main_file_link":[{"url":"https://doi.org/10.1093/brain/awac145","open_access":"1"}],"scopus_import":"1","intvolume":" 145","month":"08","acknowledged_ssus":[{"_id":"EM-Fac"},{"_id":"LifeSc"}],"abstract":[{"text":"Vacuolar-type H+-ATPase (V-ATPase) is a multimeric complex present in a variety of cellular membranes that acts as an ATP-dependent proton pump and plays a key role in pH homeostasis and intracellular signalling pathways. In humans, 22 autosomal genes encode for a redundant set of subunits allowing the composition of diverse V-ATPase complexes with specific properties and expression. Sixteen subunits have been linked to human disease.\r\nHere we describe 26 patients harbouring 20 distinct pathogenic de novo missense ATP6V1A variants, mainly clustering within the ATP synthase α/β family-nucleotide-binding domain. At a mean age of 7 years (extremes: 6 weeks, youngest deceased patient to 22 years, oldest patient) clinical pictures included early lethal encephalopathies with rapidly progressive massive brain atrophy, severe developmental epileptic encephalopathies and static intellectual disability with epilepsy. The first clinical manifestation was early hypotonia, in 70%; 81% developed epilepsy, manifested as developmental epileptic encephalopathies in 58% of the cohort and with infantile spasms in 62%; 63% of developmental epileptic encephalopathies failed to achieve any developmental, communicative or motor skills. Less severe outcomes were observed in 23% of patients who, at a mean age of 10 years and 6 months, exhibited moderate intellectual disability, with independent walking and variable epilepsy. None of the patients developed communicative language. Microcephaly (38%) and amelogenesis imperfecta/enamel dysplasia (42%) were additional clinical features. Brain MRI demonstrated hypomyelination and generalized atrophy in 68%. Atrophy was progressive in all eight individuals undergoing repeated MRIs.\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.","lang":"eng"}],"oa_version":"Published Version","department":[{"_id":"GaNo"}],"date_updated":"2023-08-04T09:13:08Z","type":"journal_article","article_type":"original","keyword":["Neurology (clinical)"],"status":"public","_id":"12174","page":"2687-2703","date_created":"2023-01-12T12:11:45Z","doi":"10.1093/brain/awac145","date_published":"2022-08-01T00:00:00Z","year":"2022","isi":1,"publication":"Brain","day":"01","oa":1,"publisher":"Oxford University Press","quality_controlled":"1","acknowledgement":"We thank all patients and family members for their participation in this study. We thank Melanie Pieraks and Eva Reinthaler (Neurolentech, Austria) for generating the human iPSC lines and\r\nfor performing quality checks. We thank Vanessa Zheden and Daniel Gütl for their excellent technical support in the specimen preparation for transmission electron microscopy and Flavia Leite for preparing the lentiviruses. The support from Electron Microscopy Facility and Molecular Biology Services at IST Austria is greatly acknowledged. We would like to thank Doctors Jane Hurst and Richard Scott for their help in retrieving the detailed clinical information of Patient 17. The research team acknowledges the support of the National Institute for Health Research, through the Comprehensive Clinical Research Network. See Supplementary Material for Undiagnosed Disease Network consortium details. Genetic information on Patient 23 was made available through access to the data and findings generated by the 100 000 Genomes\r\nProject; www.genomicsengland.co.uk (to K.L.). \r\nThis work was supported by the EU 7th Framework Programme (FP7) under the project DESIRE grant N602531 (to R.G.); the Regione Toscana under the Call for Health 2018 (grant\r\nDECODE-EE) (to R.G.); the ‘Brain Project’ by Fondazione Cassa di Risparmio di Firenze (to R.G.); IRCCS Ospedale Policlinico San Martino 5×1000 and Ricerca Corrente (to A.F. and F.B.). The European Reference Network (ERN) for rare and complex epilepsies (EpiCARE) provided financial support for meetings organization. The DDD study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between Wellcome and the Department of Health, and the Wellcome Sanger Institute (grant number WT098051). The views expressed in this publication\r\nare those of the author(s) and not necessarily those of Wellcome or the Department of Health. The study has UK Research Ethics Committee approval (10/H0305/83, granted by the Cambridge South REC, and GEN/284/12 granted by the Republic of Ireland REC). This study makes use of DECIPHER (https://www.deciphergenomics.org), which is funded by Wellcome. K.K.-S. was supported by the ISTplus fellowship. ","article_processing_charge":"No","external_id":{"isi":["000807770000001"]},"author":[{"first_name":"Renzo","full_name":"Guerrini, Renzo","last_name":"Guerrini"},{"last_name":"Mei","full_name":"Mei, Davide","first_name":"Davide"},{"last_name":"Szigeti","orcid":"0000-0001-9500-8758","full_name":"Szigeti, Margit Katalin","id":"44F4BDC0-F248-11E8-B48F-1D18A9856A87","first_name":"Margit Katalin"},{"full_name":"Pepe, Sara","last_name":"Pepe","first_name":"Sara"},{"full_name":"Koenig, Mary Kay","last_name":"Koenig","first_name":"Mary Kay"},{"full_name":"Von Allmen, Gretchen","last_name":"Von Allmen","first_name":"Gretchen"},{"first_name":"Megan T","last_name":"Cho","full_name":"Cho, Megan T"},{"last_name":"McDonald","full_name":"McDonald, Kimberly","first_name":"Kimberly"},{"first_name":"Janice","last_name":"Baker","full_name":"Baker, Janice"},{"first_name":"Vikas","full_name":"Bhambhani, Vikas","last_name":"Bhambhani"},{"first_name":"Zöe","full_name":"Powis, Zöe","last_name":"Powis"},{"first_name":"Lance","last_name":"Rodan","full_name":"Rodan, Lance"},{"first_name":"Rima","last_name":"Nabbout","full_name":"Nabbout, Rima"},{"last_name":"Barcia","full_name":"Barcia, Giulia","first_name":"Giulia"},{"first_name":"Jill A","last_name":"Rosenfeld","full_name":"Rosenfeld, Jill A"},{"full_name":"Bacino, Carlos A","last_name":"Bacino","first_name":"Carlos A"},{"first_name":"Cyril","full_name":"Mignot, Cyril","last_name":"Mignot"},{"full_name":"Power, Lillian H","last_name":"Power","first_name":"Lillian H"},{"first_name":"Catharine J","full_name":"Harris, Catharine J","last_name":"Harris"},{"first_name":"Dragan","full_name":"Marjanovic, Dragan","last_name":"Marjanovic"},{"full_name":"Møller, Rikke S","last_name":"Møller","first_name":"Rikke S"},{"full_name":"Hammer, Trine B","last_name":"Hammer","first_name":"Trine B"},{"first_name":"Riikka","last_name":"Keski Filppula","full_name":"Keski Filppula, Riikka"},{"first_name":"Päivi","full_name":"Vieira, Päivi","last_name":"Vieira"},{"last_name":"Hildebrandt","full_name":"Hildebrandt, Clara","first_name":"Clara"},{"full_name":"Sacharow, Stephanie","last_name":"Sacharow","first_name":"Stephanie"},{"full_name":"Maragliano, Luca","last_name":"Maragliano","first_name":"Luca"},{"first_name":"Fabio","full_name":"Benfenati, Fabio","last_name":"Benfenati"},{"last_name":"Lachlan","full_name":"Lachlan, Katherine","first_name":"Katherine"},{"first_name":"Andreas","full_name":"Benneche, Andreas","last_name":"Benneche"},{"last_name":"Petit","full_name":"Petit, Florence","first_name":"Florence"},{"full_name":"de Sainte Agathe, Jean Madeleine","last_name":"de Sainte Agathe","first_name":"Jean Madeleine"},{"last_name":"Hallinan","full_name":"Hallinan, Barbara","first_name":"Barbara"},{"last_name":"Si","full_name":"Si, Yue","first_name":"Yue"},{"first_name":"Ingrid M","last_name":"Wentzensen","full_name":"Wentzensen, Ingrid M"},{"first_name":"Fanggeng","last_name":"Zou","full_name":"Zou, Fanggeng"},{"first_name":"Vinodh","full_name":"Narayanan, Vinodh","last_name":"Narayanan"},{"first_name":"Naomichi","last_name":"Matsumoto","full_name":"Matsumoto, Naomichi"},{"full_name":"Boncristiano, Alessandra","last_name":"Boncristiano","first_name":"Alessandra"},{"first_name":"Giancarlo","full_name":"la Marca, Giancarlo","last_name":"la Marca"},{"first_name":"Mitsuhiro","full_name":"Kato, Mitsuhiro","last_name":"Kato"},{"last_name":"Anderson","full_name":"Anderson, Kristin","first_name":"Kristin"},{"first_name":"Carmen","full_name":"Barba, Carmen","last_name":"Barba"},{"first_name":"Luisa","full_name":"Sturiale, Luisa","last_name":"Sturiale"},{"full_name":"Garozzo, Domenico","last_name":"Garozzo","first_name":"Domenico"},{"last_name":"Bei","full_name":"Bei, Roberto","first_name":"Roberto"},{"first_name":"Laura","last_name":"Masuelli","full_name":"Masuelli, Laura"},{"full_name":"Conti, Valerio","last_name":"Conti","first_name":"Valerio"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino"},{"first_name":"Anna","full_name":"Fassio, Anna","last_name":"Fassio"}],"title":"Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal homeostasis","citation":{"ista":"Guerrini R, Mei D, Szigeti MK, Pepe S, Koenig MK, Von Allmen G, Cho MT, McDonald K, Baker J, Bhambhani V, Powis Z, Rodan L, Nabbout R, Barcia G, Rosenfeld JA, Bacino CA, Mignot C, Power LH, Harris CJ, Marjanovic D, Møller RS, Hammer TB, Keski Filppula R, Vieira P, Hildebrandt C, Sacharow S, Maragliano L, Benfenati F, Lachlan K, Benneche A, Petit F, de Sainte Agathe JM, Hallinan B, Si Y, Wentzensen IM, Zou F, Narayanan V, Matsumoto N, Boncristiano A, la Marca G, Kato M, Anderson K, Barba C, Sturiale L, Garozzo D, Bei R, Masuelli L, Conti V, Novarino G, Fassio A. 2022. Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal homeostasis. Brain. 145(8), 2687–2703.","chicago":"Guerrini, Renzo, Davide Mei, Margit Katalin Szigeti, Sara Pepe, Mary Kay Koenig, Gretchen Von Allmen, Megan T Cho, et al. “Phenotypic and Genetic Spectrum of ATP6V1A Encephalopathy: A Disorder of Lysosomal Homeostasis.” Brain. Oxford University Press, 2022. https://doi.org/10.1093/brain/awac145.","ieee":"R. Guerrini et al., “Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal homeostasis,” Brain, vol. 145, no. 8. Oxford University Press, pp. 2687–2703, 2022.","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."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","project":[{"name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411","call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425"}]}]