--- _id: '14443' abstract: - lang: eng text: "Importance Climate change, pollution, urbanization, socioeconomic inequality, and psychosocial effects of the COVID-19 pandemic have caused massive changes in environmental conditions that affect brain health during the life span, both on a population level as well as on the level of the individual. How these environmental factors influence the brain, behavior, and mental illness is not well known.\r\nObservations \ A research strategy enabling population neuroscience to contribute to identify brain mechanisms underlying environment-related mental illness by leveraging innovative enrichment tools for data federation, geospatial observation, climate and pollution measures, digital health, and novel data integration techniques is described. This strategy can inform innovative treatments that target causal cognitive and molecular mechanisms of mental illness related to the environment. An example is presented of the environMENTAL Project that is leveraging federated cohort data of over 1.5 million European citizens and patients enriched with deep phenotyping data from large-scale behavioral neuroimaging cohorts to identify brain mechanisms related to environmental adversity underlying symptoms of depression, anxiety, stress, and substance misuse.\r\nConclusions and Relevance This research will lead to the development of objective biomarkers and evidence-based interventions that will significantly improve outcomes of environment-related mental illness." article_processing_charge: No article_type: review author: - first_name: Gunter full_name: Schumann, Gunter last_name: Schumann - 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 - first_name: Nicholas full_name: Clinton, Nicholas last_name: Clinton - first_name: Sylvane full_name: Desrivieres, Sylvane last_name: Desrivieres - first_name: Ragnhild Eek full_name: Brandlistuen, Ragnhild Eek last_name: Brandlistuen - first_name: Jianfeng full_name: Feng, Jianfeng last_name: Feng - first_name: Soeren full_name: Hese, Soeren last_name: Hese - first_name: Esther full_name: Hitchen, Esther last_name: Hitchen - first_name: Per full_name: Hoffmann, Per last_name: Hoffmann - first_name: Tianye full_name: Jia, Tianye last_name: Jia - first_name: Viktor full_name: Jirsa, Viktor last_name: Jirsa - first_name: Andre F. full_name: Marquand, Andre F. last_name: Marquand - first_name: Frauke full_name: Nees, Frauke last_name: Nees - first_name: Markus M. full_name: Nöthen, Markus M. last_name: Nöthen - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 - first_name: Elli full_name: Polemiti, Elli last_name: Polemiti - first_name: Markus full_name: Ralser, Markus last_name: Ralser - first_name: Michael full_name: Rapp, Michael last_name: Rapp - first_name: Kerstin full_name: Schepanski, Kerstin last_name: Schepanski - first_name: Tamara full_name: Schikowski, Tamara last_name: Schikowski - first_name: Mel full_name: Slater, Mel last_name: Slater - first_name: Peter full_name: Sommer, Peter last_name: Sommer - first_name: Bernd Carsten full_name: Stahl, Bernd Carsten last_name: Stahl - first_name: Paul M. full_name: Thompson, Paul M. last_name: Thompson - first_name: Sven full_name: Twardziok, Sven last_name: Twardziok - first_name: Dennis full_name: Van Der Meer, Dennis last_name: Van Der Meer - first_name: Henrik full_name: Walter, Henrik last_name: Walter - first_name: Lars full_name: Westlye, Lars last_name: Westlye citation: 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' 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.' 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.' 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.' mla: 'Schumann, Gunter, et al. “Addressing Global Environmental Challenges to Mental Health Using Population Neuroscience: A Review.” JAMA Psychiatry, vol. 80, no. 10, American Medical Association, 2023, pp. 1066–74, doi:10.1001/jamapsychiatry.2023.2996.' short: G. Schumann, O.A. Andreassen, T. Banaschewski, V.D. Calhoun, N. Clinton, S. Desrivieres, R.E. Brandlistuen, J. Feng, S. Hese, E. Hitchen, P. Hoffmann, T. Jia, V. Jirsa, A.F. Marquand, F. Nees, M.M. Nöthen, G. Novarino, E. Polemiti, M. Ralser, M. Rapp, K. Schepanski, T. Schikowski, M. Slater, P. Sommer, B.C. Stahl, P.M. Thompson, S. Twardziok, D. Van Der Meer, H. Walter, L. Westlye, JAMA Psychiatry 80 (2023) 1066–1074. date_created: 2023-10-22T22:01:14Z date_published: 2023-10-01T00:00:00Z date_updated: 2023-10-31T12:17:20Z day: '01' department: - _id: GaNo doi: 10.1001/jamapsychiatry.2023.2996 external_id: pmid: - '37610741' intvolume: ' 80' issue: '10' language: - iso: eng month: '10' oa_version: None page: 1066-1074 pmid: 1 publication: JAMA Psychiatry publication_identifier: eissn: - 2168-6238 publication_status: published publisher: American Medical Association quality_controlled: '1' scopus_import: '1' status: public title: 'Addressing global environmental challenges to mental health using population neuroscience: A review' type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 80 year: '2023' ... --- _id: '14455' 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. article_number: '1287879' article_processing_charge: Yes article_type: letter_note author: - first_name: Antonio full_name: Narzisi, Antonio last_name: Narzisi - first_name: Alycia full_name: Halladay, Alycia last_name: Halladay - first_name: Gabriele full_name: Masi, Gabriele last_name: Masi - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 - first_name: Catherine full_name: Lord, Catherine last_name: Lord citation: ama: 'Narzisi A, Halladay A, Masi G, Novarino G, Lord C. Tempering expectations: Considerations on the current state of stem cells therapy for autism treatment. Frontiers in Psychiatry. 2023;14. doi:10.3389/fpsyt.2023.1287879' 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.' 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.' 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.' 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). date_created: 2023-10-29T23:01:16Z date_published: 2023-10-03T00:00:00Z date_updated: 2023-12-13T13:06:07Z day: '03' ddc: - '570' department: - _id: GaNo doi: 10.3389/fpsyt.2023.1287879 external_id: isi: - '001084841700001' pmid: - '37854442' file: - access_level: open_access checksum: 0a76373e9a4c0fc199f80380de257e86 content_type: application/pdf creator: dernst date_created: 2023-10-30T12:48:40Z date_updated: 2023-10-30T12:48:40Z file_id: '14468' file_name: 2023_FrontiersPsychiatry_Narzisi.pdf file_size: 147878 relation: main_file success: 1 file_date_updated: 2023-10-30T12:48:40Z has_accepted_license: '1' intvolume: ' 14' isi: 1 language: - iso: eng month: '10' oa: 1 oa_version: Published Version pmid: 1 publication: Frontiers in Psychiatry publication_identifier: eissn: - 1664-0640 publication_status: published publisher: Frontiers quality_controlled: '1' scopus_import: '1' status: public title: 'Tempering expectations: Considerations on the current state of stem cells therapy for autism treatment' tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 14 year: '2023' ... --- _id: '13168' 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. 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. article_processing_charge: No article_type: original author: - first_name: Jiayuan full_name: Xu, Jiayuan last_name: Xu - first_name: Nana full_name: Liu, Nana last_name: Liu - first_name: Elli full_name: Polemiti, Elli last_name: Polemiti - first_name: Liliana full_name: Garcia-Mondragon, Liliana last_name: Garcia-Mondragon - first_name: Jie full_name: Tang, Jie last_name: Tang - first_name: Xiaoxuan full_name: Liu, Xiaoxuan last_name: Liu - first_name: Tristram full_name: Lett, Tristram last_name: Lett - first_name: Le full_name: Yu, Le last_name: Yu - first_name: Markus M. full_name: Nöthen, Markus M. last_name: Nöthen - first_name: Jianfeng full_name: Feng, Jianfeng last_name: Feng - first_name: Chunshui full_name: Yu, Chunshui last_name: Yu - first_name: Andre full_name: Marquand, Andre last_name: Marquand - first_name: Gunter full_name: Schumann, Gunter last_name: Schumann - first_name: Henrik full_name: Walter, Henrik last_name: Walter - first_name: Andreas full_name: Heinz, Andreas last_name: Heinz - first_name: Markus full_name: Ralser, Markus last_name: Ralser - first_name: Sven full_name: Twardziok, Sven last_name: Twardziok - first_name: Nilakshi full_name: Vaidya, Nilakshi last_name: Vaidya - first_name: Emin full_name: Serin, Emin last_name: Serin - first_name: Marcel full_name: Jentsch, Marcel last_name: Jentsch - first_name: Esther full_name: Hitchen, Esther last_name: Hitchen - first_name: Roland full_name: Eils, Roland last_name: Eils - 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 - first_name: Jamie full_name: Banks, Jamie last_name: Banks - first_name: Tobias full_name: Banaschewski, Tobias last_name: Banaschewski - first_name: Karina full_name: Jansone, Karina last_name: Jansone - first_name: Nina full_name: Christmann, Nina last_name: Christmann - first_name: Andreas full_name: Meyer-Lindenberg, Andreas last_name: Meyer-Lindenberg - first_name: Heike full_name: Tost, Heike last_name: Tost - first_name: Nathalie full_name: Holz, Nathalie last_name: Holz - first_name: Emanuel full_name: Schwarz, Emanuel last_name: Schwarz - first_name: Argyris full_name: Stringaris, Argyris last_name: Stringaris - first_name: Maja full_name: Neidhart, Maja last_name: Neidhart - first_name: Frauke full_name: Nees, Frauke last_name: Nees - first_name: Sebastian full_name: Siehl, Sebastian last_name: Siehl - first_name: Ole full_name: A. Andreassen, Ole last_name: A. Andreassen - 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 - first_name: Rikka full_name: Kjelkenes, Rikka last_name: Kjelkenes - first_name: Helga full_name: Ask, Helga last_name: Ask - first_name: Michael full_name: Rapp, Michael last_name: Rapp - first_name: Mira full_name: Tschorn, Mira last_name: Tschorn - first_name: Sarah Jane full_name: Böttger, Sarah Jane last_name: Böttger - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 - first_name: Lena full_name: Marr, Lena id: 4406F586-F248-11E8-B48F-1D18A9856A87 last_name: Marr - first_name: Mel full_name: Slater, Mel last_name: Slater - first_name: Guillem Feixas full_name: Viapiana, Guillem Feixas last_name: Viapiana - first_name: Francisco Eiroa full_name: Orosa, Francisco Eiroa last_name: Orosa - first_name: Jaime full_name: Gallego, Jaime last_name: Gallego - first_name: Alvaro full_name: Pastor, Alvaro last_name: Pastor - first_name: Andreas full_name: Forstner, Andreas last_name: Forstner - first_name: Per full_name: Hoffmann, Per last_name: Hoffmann - first_name: Markus full_name: M. Nöthen, Markus last_name: M. Nöthen - first_name: Andreas full_name: J. Forstner, Andreas last_name: J. Forstner - first_name: Isabelle full_name: Claus, Isabelle last_name: Claus - first_name: Abbi full_name: Miller, Abbi last_name: Miller - first_name: Stefanie full_name: Heilmann-Heimbach, Stefanie last_name: Heilmann-Heimbach - first_name: Peter full_name: Sommer, Peter last_name: Sommer - first_name: Mona full_name: Boye, Mona last_name: Boye - first_name: Johannes full_name: Wilbertz, Johannes last_name: Wilbertz - first_name: Karen full_name: Schmitt, Karen last_name: Schmitt - first_name: Viktor full_name: Jirsa, Viktor last_name: Jirsa - first_name: Spase full_name: Petkoski, Spase last_name: Petkoski - first_name: Séverine full_name: Pitel, Séverine last_name: Pitel - first_name: Lisa full_name: Otten, Lisa last_name: Otten - first_name: Anastasios Polykarpos full_name: Athanasiadis, Anastasios Polykarpos last_name: Athanasiadis - first_name: Charlie full_name: Pearmund, Charlie last_name: Pearmund - first_name: Bernhard full_name: Spanlang, Bernhard last_name: Spanlang - 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 - first_name: Sören full_name: Hese, Sören last_name: Hese - first_name: Paul full_name: Renner, Paul last_name: Renner - first_name: Tianye full_name: Jia, Tianye last_name: Jia - first_name: Yanting full_name: Gong, Yanting last_name: Gong - first_name: Yunman full_name: Xia, Yunman last_name: Xia - first_name: Xiao full_name: Chang, Xiao last_name: Chang - first_name: Vince full_name: Calhoun, Vince last_name: Calhoun - first_name: Jingyu full_name: Liu, Jingyu last_name: Liu - first_name: Paul full_name: Thompson, Paul last_name: Thompson - first_name: Nicholas full_name: Clinton, Nicholas last_name: Clinton - first_name: Sylvane full_name: Desrivieres, Sylvane last_name: Desrivieres - first_name: Allan full_name: H. Young, Allan last_name: H. Young - first_name: Bernd full_name: Stahl, Bernd last_name: Stahl - first_name: George full_name: Ogoh, George last_name: Ogoh citation: ama: Xu J, Liu N, Polemiti E, et al. Effects of urban living environments on mental health in adults. Nature Medicine. 2023;29:1456-1467. doi:10.1038/s41591-023-02365-w 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 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. 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. 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. 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. 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. date_created: 2023-06-25T22:00:46Z date_published: 2023-06-15T00:00:00Z date_updated: 2023-12-13T11:25:55Z day: '15' ddc: - '570' department: - _id: GaNo doi: 10.1038/s41591-023-02365-w external_id: isi: - '001013172700001' file: - access_level: open_access checksum: bcd3225b2731c3442fa98987fd3bd46d content_type: application/pdf creator: dernst date_created: 2023-06-26T10:15:44Z date_updated: 2023-06-26T10:15:44Z file_id: '13171' file_name: 2023_NatureMedicine_Xu.pdf file_size: 7365360 relation: main_file success: 1 file_date_updated: 2023-06-26T10:15:44Z has_accepted_license: '1' intvolume: ' 29' isi: 1 language: - iso: eng month: '06' oa: 1 oa_version: Published Version page: 1456-1467 publication: Nature Medicine publication_identifier: eissn: - 1546-170X issn: - 1078-8956 publication_status: published publisher: Springer Nature quality_controlled: '1' scopus_import: '1' status: public title: Effects of urban living environments on mental health in adults tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 29 year: '2023' ... --- _id: '13267' 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 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.)." article_processing_charge: Yes article_type: original author: - first_name: Philipp full_name: Velicky, Philipp id: 39BDC62C-F248-11E8-B48F-1D18A9856A87 last_name: Velicky orcid: 0000-0002-2340-7431 - first_name: Eder full_name: Miguel Villalba, Eder id: 3FB91342-F248-11E8-B48F-1D18A9856A87 last_name: Miguel Villalba orcid: 0000-0001-5665-0430 - first_name: Julia M full_name: Michalska, Julia M id: 443DB6DE-F248-11E8-B48F-1D18A9856A87 last_name: Michalska orcid: 0000-0003-3862-1235 - first_name: Julia full_name: Lyudchik, Julia id: 46E28B80-F248-11E8-B48F-1D18A9856A87 last_name: Lyudchik - first_name: Donglai full_name: Wei, Donglai last_name: Wei - first_name: Zudi full_name: Lin, Zudi last_name: Lin - first_name: Jake full_name: Watson, Jake id: 63836096-4690-11EA-BD4E-32803DDC885E last_name: Watson orcid: 0000-0002-8698-3823 - first_name: Jakob full_name: Troidl, Jakob last_name: Troidl - first_name: Johanna full_name: Beyer, Johanna last_name: Beyer - first_name: Yoav full_name: Ben Simon, Yoav id: 43DF3136-F248-11E8-B48F-1D18A9856A87 last_name: Ben Simon - first_name: Christoph M full_name: Sommer, Christoph M id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87 last_name: Sommer orcid: 0000-0003-1216-9105 - first_name: Wiebke full_name: Jahr, Wiebke id: 425C1CE8-F248-11E8-B48F-1D18A9856A87 last_name: Jahr - first_name: Alban full_name: Cenameri, Alban id: 9ac8f577-2357-11eb-997a-e566c5550886 last_name: Cenameri - first_name: Johannes full_name: Broichhagen, Johannes last_name: Broichhagen - first_name: Seth G.N. full_name: Grant, Seth G.N. last_name: Grant - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 - first_name: Hanspeter full_name: Pfister, Hanspeter last_name: Pfister - first_name: Bernd full_name: Bickel, Bernd id: 49876194-F248-11E8-B48F-1D18A9856A87 last_name: Bickel orcid: 0000-0001-6511-9385 - first_name: Johann G full_name: Danzl, Johann G id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87 last_name: Danzl orcid: 0000-0001-8559-3973 citation: 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 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. ieee: P. Velicky et al., “Dense 4D nanoscale reconstruction of living brain tissue,” Nature Methods, vol. 20. Springer Nature, pp. 1256–1265, 2023. 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. 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. date_created: 2023-07-23T22:01:13Z date_published: 2023-08-01T00:00:00Z date_updated: 2024-01-10T08:37:48Z day: '01' department: - _id: PeJo - _id: GaNo - _id: BeBi - _id: JoDa - _id: Bio doi: 10.1038/s41592-023-01936-6 ec_funded: 1 external_id: isi: - '001025621500001' pmid: - '37429995' intvolume: ' 20' isi: 1 language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1038/s41592-023-01936-6 month: '08' oa: 1 oa_version: Published Version page: 1256-1265 pmid: 1 project: - _id: 265CB4D0-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: I03600 name: Optical control of synaptic function via adhesion molecules - _id: 2548AE96-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232-B24 name: Molecular Drug Targets - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize - _id: 23889792-32DE-11EA-91FC-C7463DDC885E name: High content imaging to decode human immune cell interactions in health and allergic disease - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program - _id: 24F9549A-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '715767' name: 'MATERIALIZABLE: Intelligent fabrication-oriented Computational Design and Modeling' - _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 - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse - _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9 call_identifier: H2020 grant_number: '101026635' name: Synaptic computations of the hippocampal CA3 circuitry - _id: 2668BFA0-B435-11E9-9278-68D0E5697425 grant_number: LT00057 name: High-speed 3D-nanoscopy to study the role of adhesion during 3D cell migration publication: Nature Methods publication_identifier: eissn: - 1548-7105 issn: - 1548-7091 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - relation: software url: https://github.com/danzllab/LIONESS record: - id: '12817' relation: research_data status: public - id: '14770' relation: shorter_version status: public scopus_import: '1' status: public title: Dense 4D nanoscale reconstruction of living brain tissue type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 20 year: '2023' ... --- _id: '14257' abstract: - lang: eng text: Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanometer synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS uses fixation-compatible extracellular labeling and optical imaging, including stimulated emission depletion or expansion microscopy, to comprehensively delineate cellular structures. It enables three-dimensional reconstruction of single synapses and mapping of synaptic connectivity by identification and analysis of putative synaptic cleft regions. Applying CATS to the mouse hippocampal mossy fiber circuitry, we reconstructed and quantified the synaptic input and output structure of identified neurons. We furthermore demonstrate applicability to clinically derived human tissue samples, including formalin-fixed paraffin-embedded routine diagnostic specimens, for visualizing the cellular architecture of brain tissue in health and disease. acknowledged_ssus: - _id: ScienComp - _id: Bio - _id: PreCl - _id: LifeSc - _id: M-Shop - _id: E-Lib 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.).' article_processing_charge: Yes (in subscription journal) article_type: original author: - first_name: Julia M full_name: Michalska, Julia M id: 443DB6DE-F248-11E8-B48F-1D18A9856A87 last_name: Michalska orcid: 0000-0003-3862-1235 - first_name: Julia full_name: Lyudchik, Julia id: 46E28B80-F248-11E8-B48F-1D18A9856A87 last_name: Lyudchik - first_name: Philipp full_name: Velicky, Philipp id: 39BDC62C-F248-11E8-B48F-1D18A9856A87 last_name: Velicky orcid: 0000-0002-2340-7431 - first_name: Hana full_name: Korinkova, Hana id: ee3cb6ca-ec98-11ea-ae11-ff703e2254ed last_name: Korinkova - first_name: Jake full_name: Watson, Jake id: 63836096-4690-11EA-BD4E-32803DDC885E last_name: Watson orcid: 0000-0002-8698-3823 - first_name: Alban full_name: Cenameri, Alban id: 9ac8f577-2357-11eb-997a-e566c5550886 last_name: Cenameri - first_name: Christoph M full_name: Sommer, Christoph M id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87 last_name: Sommer orcid: 0000-0003-1216-9105 - first_name: Nicole full_name: Amberg, Nicole id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87 last_name: Amberg orcid: 0000-0002-3183-8207 - first_name: Alessandro full_name: Venturino, Alessandro id: 41CB84B2-F248-11E8-B48F-1D18A9856A87 last_name: Venturino orcid: 0000-0003-2356-9403 - first_name: Karl full_name: Roessler, Karl last_name: Roessler - first_name: Thomas full_name: Czech, Thomas last_name: Czech - first_name: Romana full_name: Höftberger, Romana last_name: Höftberger - first_name: Sandra full_name: Siegert, Sandra id: 36ACD32E-F248-11E8-B48F-1D18A9856A87 last_name: Siegert orcid: 0000-0001-8635-0877 - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 - first_name: Johann G full_name: Danzl, Johann G id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87 last_name: Danzl orcid: 0000-0001-8559-3973 citation: 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 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. ieee: J. M. Michalska et al., “Imaging brain tissue architecture across millimeter to nanometer scales,” Nature Biotechnology. Springer Nature, 2023. ista: Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer CM, Amberg N, Venturino A, Roessler K, Czech T, Höftberger R, Siegert S, Novarino G, Jonas PM, Danzl JG. 2023. Imaging brain tissue architecture across millimeter to nanometer scales. Nature Biotechnology. 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). date_created: 2023-09-03T22:01:15Z date_published: 2023-08-31T00:00:00Z date_updated: 2024-02-21T12:18:18Z day: '31' department: - _id: SaSi - _id: GaNo - _id: PeJo - _id: JoDa - _id: Bio - _id: RySh doi: 10.1038/s41587-023-01911-8 ec_funded: 1 external_id: isi: - '001065254200001' isi: 1 language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1038/s41587-023-01911-8 month: '08' oa: 1 oa_version: Published Version project: - _id: 265CB4D0-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: I03600 name: Optical control of synaptic function via adhesion molecules - _id: 2548AE96-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232-B24 name: Molecular Drug Targets - _id: 25C5A090-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: Z00312 name: The Wittgenstein Prize - _id: 23889792-32DE-11EA-91FC-C7463DDC885E name: High content imaging to decode human immune cell interactions in health and allergic disease - _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 - _id: 25B7EB9E-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '692692' name: Biophysics and circuit function of a giant cortical glumatergic synapse - _id: 2564DBCA-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '665385' name: International IST Doctoral Program - _id: fc2be41b-9c52-11eb-aca3-faa90aa144e9 call_identifier: H2020 grant_number: '101026635' name: Synaptic computations of the hippocampal CA3 circuitry publication: Nature Biotechnology publication_identifier: eissn: - 1546-1696 issn: - 1087-0156 publication_status: epub_ahead publisher: Springer Nature quality_controlled: '1' related_material: link: - relation: software url: https://github.com/danzllab/CATS record: - id: '13126' relation: research_data status: public scopus_import: '1' status: public title: Imaging brain tissue architecture across millimeter to nanometer scales type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2023' ... --- _id: '12802' 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 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. article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Lisa full_name: Knaus, Lisa id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87 last_name: Knaus - first_name: Bernadette full_name: Basilico, Bernadette id: 36035796-5ACA-11E9-A75E-7AF2E5697425 last_name: Basilico orcid: 0000-0003-1843-3173 - first_name: Daniel full_name: Malzl, Daniel last_name: Malzl - first_name: Maria full_name: Gerykova Bujalkova, Maria last_name: Gerykova Bujalkova - first_name: Mateja full_name: Smogavec, Mateja last_name: Smogavec - first_name: Lena A. full_name: Schwarz, Lena A. last_name: Schwarz - first_name: Sarah full_name: Gorkiewicz, Sarah id: f141a35d-15a9-11ec-9fb2-fef6becc7b6f last_name: Gorkiewicz - first_name: Nicole full_name: Amberg, Nicole id: 4CD6AAC6-F248-11E8-B48F-1D18A9856A87 last_name: Amberg orcid: 0000-0002-3183-8207 - first_name: Florian full_name: Pauler, Florian id: 48EA0138-F248-11E8-B48F-1D18A9856A87 last_name: Pauler orcid: 0000-0002-7462-0048 - first_name: Christian full_name: Knittl-Frank, Christian last_name: Knittl-Frank - first_name: Marianna full_name: Tassinari, Marianna id: 7af593f1-d44a-11ed-bf94-a3646a6bb35e last_name: Tassinari - first_name: Nuno full_name: Maulide, Nuno last_name: Maulide - first_name: Thomas full_name: Rülicke, Thomas last_name: Rülicke - first_name: Jörg full_name: Menche, Jörg last_name: Menche - first_name: Simon full_name: Hippenmeyer, Simon id: 37B36620-F248-11E8-B48F-1D18A9856A87 last_name: Hippenmeyer orcid: 0000-0003-2279-1061 - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 citation: ama: Knaus L, Basilico B, Malzl D, et al. Large neutral amino acid levels tune perinatal neuronal excitability and survival. Cell. 2023;186(9):1950-1967.e25. doi:10.1016/j.cell.2023.02.037 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 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. 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. 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. date_created: 2023-04-05T08:15:40Z date_published: 2023-04-27T00:00:00Z date_updated: 2024-02-07T08:03:32Z day: '27' ddc: - '570' department: - _id: SiHi - _id: GaNo doi: 10.1016/j.cell.2023.02.037 ec_funded: 1 external_id: isi: - '000991468700001' file: - access_level: open_access checksum: 47e94fbe19e86505b429cb7a5b503ce6 content_type: application/pdf creator: dernst date_created: 2023-05-02T09:26:21Z date_updated: 2023-05-02T09:26:21Z file_id: '12889' file_name: 2023_Cell_Knaus.pdf file_size: 15712841 relation: main_file success: 1 file_date_updated: 2023-05-02T09:26:21Z has_accepted_license: '1' intvolume: ' 186' isi: 1 issue: '9' keyword: - General Biochemistry - Genetics and Molecular Biology language: - iso: eng month: '04' oa: 1 oa_version: Published Version page: 1950-1967.e25 project: - _id: 2548AE96-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232-B24 name: Molecular Drug Targets - _id: 260018B0-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '725780' name: Principles of Neural Stem Cell Lineage Progression in Cerebral Cortex Development - _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 publication: Cell publication_identifier: issn: - 0092-8674 publication_status: published publisher: Elsevier quality_controlled: '1' related_material: link: - description: News on ISTA Website relation: press_release url: https://ista.ac.at/en/news/feed-them-or-lose-them/ record: - id: '13107' relation: dissertation_contains status: public scopus_import: '1' status: public title: Large neutral amino acid levels tune perinatal neuronal excitability and survival tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 186 year: '2023' ... --- _id: '11160' 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 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. article_number: '110615' article_processing_charge: Yes article_type: original author: - first_name: Carlo Emanuele full_name: Villa, Carlo Emanuele last_name: Villa - first_name: Cristina full_name: Cheroni, Cristina last_name: Cheroni - first_name: Christoph full_name: Dotter, Christoph id: 4C66542E-F248-11E8-B48F-1D18A9856A87 last_name: Dotter orcid: 0000-0002-9033-9096 - first_name: Alejandro full_name: López-Tóbon, Alejandro last_name: López-Tóbon - first_name: Bárbara full_name: Oliveira, Bárbara id: 3B03AA1A-F248-11E8-B48F-1D18A9856A87 last_name: Oliveira - first_name: Roberto full_name: Sacco, Roberto id: 42C9F57E-F248-11E8-B48F-1D18A9856A87 last_name: Sacco - first_name: Aysan Çerağ full_name: Yahya, Aysan Çerağ id: 365A65F8-F248-11E8-B48F-1D18A9856A87 last_name: Yahya - first_name: Jasmin full_name: Morandell, Jasmin id: 4739D480-F248-11E8-B48F-1D18A9856A87 last_name: Morandell - first_name: Michele full_name: Gabriele, Michele last_name: Gabriele - first_name: Mojtaba full_name: Tavakoli, Mojtaba id: 3A0A06F4-F248-11E8-B48F-1D18A9856A87 last_name: Tavakoli orcid: 0000-0002-7667-6854 - first_name: Julia full_name: Lyudchik, Julia id: 46E28B80-F248-11E8-B48F-1D18A9856A87 last_name: Lyudchik - first_name: Christoph M full_name: Sommer, Christoph M id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87 last_name: Sommer orcid: 0000-0003-1216-9105 - first_name: Mariano full_name: Gabitto, Mariano last_name: Gabitto - first_name: Johann G full_name: Danzl, Johann G id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87 last_name: Danzl orcid: 0000-0001-8559-3973 - first_name: Giuseppe full_name: Testa, Giuseppe last_name: Testa - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 citation: ama: Villa CE, Cheroni C, Dotter C, et al. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. Cell Reports. 2022;39(1). doi:10.1016/j.celrep.2022.110615 apa: Villa, C. E., Cheroni, C., Dotter, C., López-Tóbon, A., Oliveira, B., Sacco, R., … Novarino, G. (2022). CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. Cell Reports. Elsevier. https://doi.org/10.1016/j.celrep.2022.110615 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. ieee: C. E. Villa et al., “CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories,” Cell Reports, vol. 39, no. 1. Elsevier, 2022. ista: Villa CE, Cheroni C, Dotter C, López-Tóbon A, Oliveira B, Sacco R, Yahya AÇ, Morandell J, Gabriele M, Tavakoli M, Lyudchik J, Sommer CM, Gabitto M, Danzl JG, Testa G, Novarino G. 2022. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. Cell Reports. 39(1), 110615. mla: Villa, Carlo Emanuele, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” Cell Reports, vol. 39, no. 1, 110615, Elsevier, 2022, doi:10.1016/j.celrep.2022.110615. short: C.E. Villa, C. Cheroni, C. Dotter, A. López-Tóbon, B. Oliveira, R. Sacco, A.Ç. Yahya, J. Morandell, M. Gabriele, M. Tavakoli, J. Lyudchik, C.M. Sommer, M. Gabitto, J.G. Danzl, G. Testa, G. Novarino, Cell Reports 39 (2022). date_created: 2022-04-15T09:03:10Z date_published: 2022-04-05T00:00:00Z date_updated: 2024-03-25T23:30:25Z day: '05' ddc: - '570' department: - _id: JoDa - _id: GaNo doi: 10.1016/j.celrep.2022.110615 ec_funded: 1 external_id: isi: - '000785983900003' pmid: - '35385734' file: - access_level: open_access checksum: b4e8d68f0268dec499af333e6fd5d8e1 content_type: application/pdf creator: dernst date_created: 2022-04-15T09:06:25Z date_updated: 2022-04-15T09:06:25Z file_id: '11164' file_name: 2022_CellReports_Villa.pdf file_size: '7808644' relation: main_file success: 1 file_date_updated: 2022-04-15T09:06:25Z has_accepted_license: '1' intvolume: ' 39' isi: 1 issue: '1' keyword: - General Biochemistry - Genetics and Molecular Biology language: - iso: eng month: '04' oa: 1 oa_version: Published Version pmid: 1 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 - _id: 2690FEAC-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: I04205 name: Identification of converging Molecular Pathways Across Chromatinopathies as Targets for Therapy publication: Cell Reports publication_identifier: issn: - 2211-1247 publication_status: published publisher: Elsevier quality_controlled: '1' related_material: record: - id: '12364' relation: dissertation_contains status: public status: public title: CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87 volume: 39 year: '2022' ... --- _id: '11943' 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. article_processing_charge: No author: - first_name: Philipp full_name: Velicky, Philipp id: 39BDC62C-F248-11E8-B48F-1D18A9856A87 last_name: Velicky orcid: 0000-0002-2340-7431 - first_name: Eder full_name: Miguel Villalba, Eder id: 3FB91342-F248-11E8-B48F-1D18A9856A87 last_name: Miguel Villalba orcid: 0000-0001-5665-0430 - first_name: Julia M full_name: Michalska, Julia M id: 443DB6DE-F248-11E8-B48F-1D18A9856A87 last_name: Michalska orcid: 0000-0003-3862-1235 - first_name: Donglai full_name: Wei, Donglai last_name: Wei - first_name: Zudi full_name: Lin, Zudi last_name: Lin - first_name: Jake full_name: Watson, Jake id: 63836096-4690-11EA-BD4E-32803DDC885E last_name: Watson orcid: 0000-0002-8698-3823 - first_name: Jakob full_name: Troidl, Jakob last_name: Troidl - first_name: Johanna full_name: Beyer, Johanna last_name: Beyer - first_name: Yoav full_name: Ben Simon, Yoav id: 43DF3136-F248-11E8-B48F-1D18A9856A87 last_name: Ben Simon - first_name: Christoph M full_name: Sommer, Christoph M id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87 last_name: Sommer orcid: 0000-0003-1216-9105 - first_name: Wiebke full_name: Jahr, Wiebke id: 425C1CE8-F248-11E8-B48F-1D18A9856A87 last_name: Jahr - first_name: Alban full_name: Cenameri, Alban id: 9ac8f577-2357-11eb-997a-e566c5550886 last_name: Cenameri - first_name: Johannes full_name: Broichhagen, Johannes last_name: Broichhagen - first_name: Seth G. N. full_name: Grant, Seth G. N. last_name: Grant - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 - first_name: Hanspeter full_name: Pfister, Hanspeter last_name: Pfister - first_name: Bernd full_name: Bickel, Bernd id: 49876194-F248-11E8-B48F-1D18A9856A87 last_name: Bickel orcid: 0000-0001-6511-9385 - first_name: Johann G full_name: Danzl, Johann G id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87 last_name: Danzl orcid: 0000-0001-8559-3973 citation: 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 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. ieee: P. Velicky et al., “Saturated reconstruction of living brain tissue,” bioRxiv. Cold Spring Harbor Laboratory. ista: Velicky P, Miguel Villalba E, Michalska JM, Wei D, Lin Z, Watson J, Troidl J, Beyer J, Ben Simon Y, Sommer CM, Jahr W, Cenameri A, Broichhagen J, Grant SGN, Jonas PM, Novarino G, Pfister H, Bickel B, Danzl JG. Saturated reconstruction of living brain tissue. bioRxiv, 10.1101/2022.03.16.484431. mla: Velicky, Philipp, et al. “Saturated Reconstruction of Living Brain Tissue.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2022.03.16.484431. short: P. Velicky, E. Miguel Villalba, J.M. Michalska, D. Wei, Z. Lin, J. Watson, J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri, J. Broichhagen, S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel, J.G. Danzl, BioRxiv (n.d.). date_created: 2022-08-23T11:07:59Z date_published: 2022-05-09T00:00:00Z date_updated: 2024-03-25T23:30:11Z day: '09' department: - _id: PeJo - _id: GaNo - _id: BeBi - _id: JoDa doi: 10.1101/2022.03.16.484431 language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1101/2022.03.16.484431 month: '05' oa: 1 oa_version: Preprint publication: bioRxiv publication_status: submitted publisher: Cold Spring Harbor Laboratory related_material: record: - id: '12470' relation: dissertation_contains status: public status: public title: Saturated reconstruction of living brain tissue type: preprint user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2022' ... --- _id: '11950' abstract: - lang: eng text: Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanoscopic synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS leverages fixation-compatible extracellular labeling and advanced optical readout, in particular stimulated-emission depletion and expansion microscopy, to comprehensively delineate cellular structures. It enables 3D-reconstructing single synapses and mapping synaptic connectivity by identification and tailored analysis of putative synaptic cleft regions. Applying CATS to the hippocampal mossy fiber circuitry, we demonstrate its power to reveal the system’s molecularly informed ultrastructure across spatial scales and assess local connectivity by reconstructing and quantifying the synaptic input and output structure of identified neurons. article_processing_charge: No author: - first_name: Julia M full_name: Michalska, Julia M id: 443DB6DE-F248-11E8-B48F-1D18A9856A87 last_name: Michalska orcid: 0000-0003-3862-1235 - first_name: Julia full_name: Lyudchik, Julia id: 46E28B80-F248-11E8-B48F-1D18A9856A87 last_name: Lyudchik - first_name: Philipp full_name: Velicky, Philipp id: 39BDC62C-F248-11E8-B48F-1D18A9856A87 last_name: Velicky orcid: 0000-0002-2340-7431 - first_name: Hana full_name: Korinkova, Hana id: ee3cb6ca-ec98-11ea-ae11-ff703e2254ed last_name: Korinkova - first_name: Jake full_name: Watson, Jake id: 63836096-4690-11EA-BD4E-32803DDC885E last_name: Watson orcid: 0000-0002-8698-3823 - first_name: Alban full_name: Cenameri, Alban id: 9ac8f577-2357-11eb-997a-e566c5550886 last_name: Cenameri - first_name: Christoph M full_name: Sommer, Christoph M id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87 last_name: Sommer orcid: 0000-0003-1216-9105 - first_name: Alessandro full_name: Venturino, Alessandro id: 41CB84B2-F248-11E8-B48F-1D18A9856A87 last_name: Venturino orcid: 0000-0003-2356-9403 - first_name: Karl full_name: Roessler, Karl last_name: Roessler - first_name: Thomas full_name: Czech, Thomas last_name: Czech - first_name: Sandra full_name: Siegert, Sandra id: 36ACD32E-F248-11E8-B48F-1D18A9856A87 last_name: Siegert orcid: 0000-0001-8635-0877 - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 - first_name: Peter M full_name: Jonas, Peter M id: 353C1B58-F248-11E8-B48F-1D18A9856A87 last_name: Jonas orcid: 0000-0001-5001-4804 - first_name: Johann G full_name: Danzl, Johann G id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87 last_name: Danzl orcid: 0000-0001-8559-3973 citation: ama: Michalska JM, Lyudchik J, Velicky P, et al. Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv. doi:10.1101/2022.08.17.504272 apa: Michalska, J. M., Lyudchik, J., Velicky, P., Korinkova, H., Watson, J., Cenameri, A., … Danzl, J. G. (n.d.). Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2022.08.17.504272 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. ieee: J. M. Michalska et al., “Uncovering brain tissue architecture across scales with super-resolution light microscopy,” bioRxiv. Cold Spring Harbor Laboratory. ista: Michalska JM, Lyudchik J, Velicky P, Korinkova H, Watson J, Cenameri A, Sommer CM, Venturino A, Roessler K, Czech T, Siegert S, Novarino G, Jonas PM, Danzl JG. Uncovering brain tissue architecture across scales with super-resolution light microscopy. bioRxiv, 10.1101/2022.08.17.504272. 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. 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.). date_created: 2022-08-24T08:24:52Z date_published: 2022-08-18T00:00:00Z date_updated: 2024-03-25T23:30:11Z day: '18' department: - _id: SaSi - _id: GaNo - _id: PeJo - _id: JoDa doi: 10.1101/2022.08.17.504272 language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1101/2022.08.17.504272 month: '08' oa: 1 oa_version: Preprint publication: bioRxiv publication_status: submitted publisher: Cold Spring Harbor Laboratory related_material: record: - id: '12470' relation: dissertation_contains status: public status: public title: Uncovering brain tissue architecture across scales with super-resolution light microscopy type: preprint user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2022' ... --- _id: '12174' 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 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 article_type: original author: - first_name: Renzo full_name: Guerrini, Renzo last_name: Guerrini - first_name: Davide full_name: Mei, Davide last_name: Mei - first_name: Margit Katalin full_name: Szigeti, Margit Katalin id: 44F4BDC0-F248-11E8-B48F-1D18A9856A87 last_name: Szigeti orcid: 0000-0001-9500-8758 - first_name: Sara full_name: Pepe, Sara last_name: Pepe - first_name: Mary Kay full_name: Koenig, Mary Kay last_name: Koenig - first_name: Gretchen full_name: Von Allmen, Gretchen last_name: Von Allmen - first_name: Megan T full_name: Cho, Megan T last_name: Cho - first_name: Kimberly full_name: McDonald, Kimberly last_name: McDonald - first_name: Janice full_name: Baker, Janice last_name: Baker - first_name: Vikas full_name: Bhambhani, Vikas last_name: Bhambhani - first_name: Zöe full_name: Powis, Zöe last_name: Powis - first_name: Lance full_name: Rodan, Lance last_name: Rodan - first_name: Rima full_name: Nabbout, Rima last_name: Nabbout - first_name: Giulia full_name: Barcia, Giulia last_name: Barcia - first_name: Jill A full_name: Rosenfeld, Jill A last_name: Rosenfeld - first_name: Carlos A full_name: Bacino, Carlos A last_name: Bacino - first_name: Cyril full_name: Mignot, Cyril last_name: Mignot - first_name: Lillian H full_name: Power, Lillian H last_name: Power - first_name: Catharine J full_name: Harris, Catharine J last_name: Harris - first_name: Dragan full_name: Marjanovic, Dragan last_name: Marjanovic - first_name: Rikke S full_name: Møller, Rikke S last_name: Møller - first_name: Trine B full_name: Hammer, Trine B last_name: Hammer - first_name: Riikka full_name: Keski Filppula, Riikka last_name: Keski Filppula - first_name: Päivi full_name: Vieira, Päivi last_name: Vieira - first_name: Clara full_name: Hildebrandt, Clara last_name: Hildebrandt - first_name: Stephanie full_name: Sacharow, Stephanie last_name: Sacharow - first_name: Luca full_name: Maragliano, Luca last_name: Maragliano - first_name: Fabio full_name: Benfenati, Fabio last_name: Benfenati - first_name: Katherine full_name: Lachlan, Katherine last_name: Lachlan - first_name: Andreas full_name: Benneche, Andreas last_name: Benneche - first_name: Florence full_name: Petit, Florence last_name: Petit - first_name: Jean Madeleine full_name: de Sainte Agathe, Jean Madeleine last_name: de Sainte Agathe - first_name: Barbara full_name: Hallinan, Barbara last_name: Hallinan - first_name: Yue full_name: Si, Yue last_name: Si - first_name: Ingrid M full_name: Wentzensen, Ingrid M last_name: Wentzensen - first_name: Fanggeng full_name: Zou, Fanggeng last_name: Zou - first_name: Vinodh full_name: Narayanan, Vinodh last_name: Narayanan - first_name: Naomichi full_name: Matsumoto, Naomichi last_name: Matsumoto - first_name: Alessandra full_name: Boncristiano, Alessandra last_name: Boncristiano - first_name: Giancarlo full_name: la Marca, Giancarlo last_name: la Marca - first_name: Mitsuhiro full_name: Kato, Mitsuhiro last_name: Kato - first_name: Kristin full_name: Anderson, Kristin last_name: Anderson - first_name: Carmen full_name: Barba, Carmen last_name: Barba - first_name: Luisa full_name: Sturiale, Luisa last_name: Sturiale - first_name: Domenico full_name: Garozzo, Domenico last_name: Garozzo - first_name: Roberto full_name: Bei, Roberto last_name: Bei - first_name: Laura full_name: Masuelli, Laura last_name: Masuelli - first_name: Valerio full_name: Conti, Valerio last_name: Conti - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 - first_name: Anna full_name: Fassio, Anna last_name: Fassio citation: 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' 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.' 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.' 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.' 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. date_created: 2023-01-12T12:11:45Z date_published: 2022-08-01T00:00:00Z date_updated: 2023-08-04T09:13:08Z day: '01' department: - _id: GaNo doi: 10.1093/brain/awac145 ec_funded: 1 external_id: isi: - '000807770000001' intvolume: ' 145' isi: 1 issue: '8' keyword: - Neurology (clinical) language: - iso: eng main_file_link: - open_access: '1' url: https://doi.org/10.1093/brain/awac145 month: '08' oa: 1 oa_version: Published Version page: 2687-2703 project: - _id: 260C2330-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '754411' name: ISTplus - Postdoctoral Fellowships publication: Brain publication_identifier: eissn: - 1460-2156 issn: - 0006-8950 publication_status: published publisher: Oxford University Press quality_controlled: '1' scopus_import: '1' status: public title: 'Phenotypic and genetic spectrum of ATP6V1A encephalopathy: A disorder of lysosomal homeostasis' type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 145 year: '2022' ... --- _id: '8730' abstract: - lang: eng text: P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) restrict at the blood–brain barrier (BBB) the brain distribution of the majority of currently known molecularly targeted anticancer drugs. To improve brain delivery of dual ABCB1/ABCG2 substrates, both ABCB1 and ABCG2 need to be inhibited simultaneously at the BBB. We examined the feasibility of simultaneous ABCB1/ABCG2 inhibition with i.v. co-infusion of erlotinib and tariquidar by studying brain distribution of the model ABCB1/ABCG2 substrate [11C]erlotinib in mice and rhesus macaques with PET. Tolerability of the erlotinib/tariquidar combination was assessed in human embryonic stem cell-derived cerebral organoids. In mice and macaques, baseline brain distribution of [11C]erlotinib was low (brain distribution volume, VT,brain < 0.3 mL/cm3). Co-infusion of erlotinib and tariquidar increased VT,brain in mice by 3.0-fold and in macaques by 3.4- to 5.0-fold, while infusion of erlotinib alone or tariquidar alone led to less pronounced VT,brain increases in both species. Treatment of cerebral organoids with erlotinib/tariquidar led to an induction of Caspase-3-dependent apoptosis. Co-infusion of erlotinib/tariquidar may potentially allow for complete ABCB1/ABCG2 inhibition at the BBB, while simultaneously achieving brain-targeted EGFR inhibition. Our protocol may be applicable to enhance brain delivery of molecularly targeted anticancer drugs for a more effective treatment of brain tumors. article_processing_charge: No article_type: original author: - first_name: N full_name: Tournier, N last_name: Tournier - first_name: S full_name: Goutal, S last_name: Goutal - first_name: S full_name: Mairinger, S last_name: Mairinger - first_name: IH full_name: Lozano, IH last_name: Lozano - first_name: T full_name: Filip, T last_name: Filip - first_name: M full_name: Sauberer, M last_name: Sauberer - first_name: F full_name: Caillé, F last_name: Caillé - first_name: L full_name: Breuil, L last_name: Breuil - first_name: J full_name: Stanek, J last_name: Stanek - first_name: AF full_name: Freeman, AF last_name: Freeman - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 - first_name: C full_name: Truillet, C last_name: Truillet - first_name: T full_name: Wanek, T last_name: Wanek - first_name: O full_name: Langer, O last_name: Langer citation: ama: Tournier N, Goutal S, Mairinger S, et al. Complete inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion of erlotinib and tariquidar to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib. 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 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. 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. 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. 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. date_created: 2020-11-06T08:39:01Z date_published: 2021-07-01T00:00:00Z date_updated: 2023-10-18T06:45:30Z day: '01' department: - _id: GaNo doi: 10.1177/0271678X20965500 external_id: isi: - '000664214100012' pmid: - '33081568' intvolume: ' 41' isi: 1 issue: '7' language: - iso: eng main_file_link: - open_access: '1' url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221757/ month: '07' oa: 1 oa_version: Published Version page: 1634-1646 pmid: 1 publication: Journal of Cerebral Blood Flow and Metabolism publication_identifier: eissn: - 1559-7016 issn: - 0271-678x publication_status: published publisher: SAGE Publications quality_controlled: '1' scopus_import: '1' status: public title: Complete inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion of erlotinib and tariquidar to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 41 year: '2021' ... --- _id: '9429' 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. acknowledged_ssus: - _id: PreCl 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). article_number: '3058' article_processing_charge: No article_type: original author: - first_name: Jasmin full_name: Morandell, Jasmin id: 4739D480-F248-11E8-B48F-1D18A9856A87 last_name: Morandell - first_name: Lena A full_name: Schwarz, Lena A id: 29A8453C-F248-11E8-B48F-1D18A9856A87 last_name: Schwarz - first_name: Bernadette full_name: Basilico, Bernadette id: 36035796-5ACA-11E9-A75E-7AF2E5697425 last_name: Basilico orcid: 0000-0003-1843-3173 - first_name: Saren full_name: Tasciyan, Saren id: 4323B49C-F248-11E8-B48F-1D18A9856A87 last_name: Tasciyan orcid: 0000-0003-1671-393X - first_name: Georgi A full_name: Dimchev, Georgi A id: 38C393BE-F248-11E8-B48F-1D18A9856A87 last_name: Dimchev orcid: 0000-0001-8370-6161 - first_name: Armel full_name: Nicolas, Armel id: 2A103192-F248-11E8-B48F-1D18A9856A87 last_name: Nicolas - first_name: Christoph M full_name: Sommer, Christoph M id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87 last_name: Sommer orcid: 0000-0003-1216-9105 - first_name: Caroline full_name: Kreuzinger, Caroline id: 382077BA-F248-11E8-B48F-1D18A9856A87 last_name: Kreuzinger - first_name: Christoph full_name: Dotter, Christoph id: 4C66542E-F248-11E8-B48F-1D18A9856A87 last_name: Dotter orcid: 0000-0002-9033-9096 - first_name: Lisa full_name: Knaus, Lisa id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87 last_name: Knaus - first_name: Zoe full_name: Dobler, Zoe id: D23090A2-9057-11EA-883A-A8396FC7A38F last_name: Dobler - first_name: Emanuele full_name: Cacci, Emanuele last_name: Cacci - first_name: Florian KM full_name: Schur, Florian KM id: 48AD8942-F248-11E8-B48F-1D18A9856A87 last_name: Schur orcid: 0000-0003-4790-8078 - first_name: Johann G full_name: Danzl, Johann G id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87 last_name: Danzl orcid: 0000-0001-8559-3973 - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 citation: ama: Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. 2021;12(1). doi:10.1038/s41467-021-23123-x 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 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. ieee: J. Morandell et al., “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” Nature Communications, vol. 12, no. 1. Springer Nature, 2021. ista: Morandell J, Schwarz LA, Basilico B, Tasciyan S, Dimchev GA, Nicolas A, Sommer CM, Kreuzinger C, Dotter C, Knaus L, Dobler Z, Cacci E, Schur FK, Danzl JG, Novarino G. 2021. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. 12(1), 3058. mla: Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” Nature Communications, vol. 12, no. 1, 3058, Springer Nature, 2021, doi:10.1038/s41467-021-23123-x. short: J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, G.A. Dimchev, A. Nicolas, C.M. Sommer, C. Kreuzinger, C. Dotter, L. Knaus, Z. Dobler, E. Cacci, F.K. Schur, J.G. Danzl, G. Novarino, Nature Communications 12 (2021). date_created: 2021-05-28T11:49:46Z date_published: 2021-05-24T00:00:00Z date_updated: 2024-09-10T12:04:26Z day: '24' ddc: - '572' department: - _id: GaNo - _id: JoDa - _id: FlSc - _id: MiSi - _id: LifeSc - _id: Bio doi: 10.1038/s41467-021-23123-x ec_funded: 1 external_id: isi: - '000658769900010' file: - access_level: open_access checksum: 337e0f7959c35ec959984cacdcb472ba content_type: application/pdf creator: kschuh date_created: 2021-05-28T12:39:43Z date_updated: 2021-05-28T12:39:43Z file_id: '9430' file_name: 2021_NatureCommunications_Morandell.pdf file_size: 9358599 relation: main_file success: 1 file_date_updated: 2021-05-28T12:39:43Z has_accepted_license: '1' intvolume: ' 12' isi: 1 issue: '1' keyword: - General Biochemistry - Genetics and Molecular Biology language: - iso: eng month: '05' oa: 1 oa_version: Published Version project: - _id: 260C2330-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '754411' name: ISTplus - Postdoctoral Fellowships - _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 - _id: 2548AE96-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232-B24 name: Molecular Drug Targets - _id: 05A0D778-7A3F-11EA-A408-12923DDC885E grant_number: F07807 name: Neural stem cells in autism and epilepsy - _id: 265CB4D0-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: I03600 name: Optical control of synaptic function via adhesion molecules publication: Nature Communications publication_identifier: eissn: - 2041-1723 publication_status: published publisher: Springer Nature quality_controlled: '1' related_material: link: - relation: press_release url: https://ist.ac.at/en/news/defective-gene-slows-down-brain-cells/ record: - id: '7800' relation: earlier_version status: public - id: '12401' relation: dissertation_contains status: public status: public title: Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 12 year: '2021' ... --- _id: '10281' abstract: - lang: eng 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 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.' alternative_title: - Special Issue "From Genes to Therapy in Autism Spectrum Disorder" article_number: '1746' article_processing_charge: No article_type: original author: - first_name: Verica full_name: Vasic, Verica last_name: Vasic - first_name: Mattson S.O. full_name: Jones, Mattson S.O. last_name: Jones - first_name: Denise full_name: Haslinger, Denise id: 76922BDA-3D3B-11EA-90BD-A44F3DDC885E last_name: Haslinger - first_name: Lisa full_name: Knaus, Lisa id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87 last_name: Knaus - first_name: Michael J. full_name: Schmeisser, Michael J. last_name: Schmeisser - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 - first_name: Andreas G. full_name: Chiocchetti, Andreas G. last_name: Chiocchetti citation: 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' 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' 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.' 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.' 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.' 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). date_created: 2021-11-14T23:01:24Z date_published: 2021-10-30T00:00:00Z date_updated: 2023-08-14T11:46:12Z day: '30' ddc: - '570' department: - _id: GaNo doi: 10.3390/genes12111746 ec_funded: 1 external_id: isi: - '000834044200002' file: - access_level: open_access checksum: 256cb832a9c3051c7dc741f6423b8cbd content_type: application/pdf creator: dernst date_created: 2022-05-16T07:02:27Z date_updated: 2022-05-16T07:02:27Z file_id: '11380' file_name: 2021_Genes_Vasic.pdf file_size: 1335308 relation: main_file success: 1 file_date_updated: 2022-05-16T07:02:27Z has_accepted_license: '1' intvolume: ' 12' isi: 1 issue: '11' language: - iso: eng month: '10' oa: 1 oa_version: Published Version 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 - _id: 2548AE96-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232-B24 name: Molecular Drug Targets publication: Genes publication_identifier: eissn: - 2073-4425 publication_status: published publisher: MDPI quality_controlled: '1' scopus_import: '1' status: public title: 'Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment' tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 12 year: '2021' ... --- _id: '7800' 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 article_processing_charge: No author: - first_name: Jasmin full_name: Morandell, Jasmin id: 4739D480-F248-11E8-B48F-1D18A9856A87 last_name: Morandell - first_name: Lena A full_name: Schwarz, Lena A id: 29A8453C-F248-11E8-B48F-1D18A9856A87 last_name: Schwarz - first_name: Bernadette full_name: Basilico, Bernadette id: 36035796-5ACA-11E9-A75E-7AF2E5697425 last_name: Basilico orcid: 0000-0003-1843-3173 - first_name: Saren full_name: Tasciyan, Saren id: 4323B49C-F248-11E8-B48F-1D18A9856A87 last_name: Tasciyan orcid: 0000-0003-1671-393X - first_name: Armel full_name: Nicolas, Armel id: 2A103192-F248-11E8-B48F-1D18A9856A87 last_name: Nicolas - first_name: Christoph M full_name: Sommer, Christoph M id: 4DF26D8C-F248-11E8-B48F-1D18A9856A87 last_name: Sommer orcid: 0000-0003-1216-9105 - first_name: Caroline full_name: Kreuzinger, Caroline id: 382077BA-F248-11E8-B48F-1D18A9856A87 last_name: Kreuzinger - first_name: Lisa full_name: Knaus, Lisa id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87 last_name: Knaus - first_name: Zoe full_name: Dobler, Zoe id: D23090A2-9057-11EA-883A-A8396FC7A38F last_name: Dobler - first_name: Emanuele full_name: Cacci, Emanuele last_name: Cacci - first_name: Johann G full_name: Danzl, Johann G id: 42EFD3B6-F248-11E8-B48F-1D18A9856A87 last_name: Danzl orcid: 0000-0001-8559-3973 - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 citation: ama: Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. bioRxiv. doi:10.1101/2020.01.10.902064 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 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 . 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. 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 . 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 . 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.). date_created: 2020-05-05T14:31:33Z date_published: 2020-01-11T00:00:00Z date_updated: 2024-09-10T12:04:26Z day: '11' ddc: - '570' department: - _id: JoDa - _id: GaNo - _id: LifeSc doi: '10.1101/2020.01.10.902064 ' file: - access_level: open_access checksum: c6799ab5daba80efe8e2ed63c15f8c81 content_type: application/pdf creator: rsix date_created: 2020-05-05T14:31:19Z date_updated: 2020-07-14T12:48:03Z file_id: '7801' file_name: 2020.01.10.902064v1.full.pdf file_size: 2931370 relation: main_file file_date_updated: 2020-07-14T12:48:03Z has_accepted_license: '1' language: - iso: eng month: '01' oa: 1 oa_version: Preprint project: - _id: 265CB4D0-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: I03600 name: Optical control of synaptic function via adhesion molecules - _id: 2548AE96-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232-B24 name: Molecular Drug Targets publication: bioRxiv publication_status: submitted publisher: Cold Spring Harbor Laboratory related_material: record: - id: '8620' relation: dissertation_contains status: public - id: '9429' relation: later_version status: public status: public title: Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: preprint user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 year: '2020' ... --- _id: '7957' 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." acknowledgement: We wish to thank Jasmin Morandell for generously sharing Figure 2. This work was supported by the European Research Council Starting Grant (grant 715508 ) to G.N. article_processing_charge: No article_type: original author: - first_name: Ilaria full_name: Parenti, Ilaria id: D93538B0-5B71-11E9-AC62-02EBE5697425 last_name: Parenti - first_name: Luis E full_name: Garcia Rabaneda, Luis E id: 33D1B084-F248-11E8-B48F-1D18A9856A87 last_name: Garcia Rabaneda - first_name: Hanna full_name: Schön, Hanna id: C8E17EDC-D7AA-11E9-B7B7-45ECE5697425 last_name: Schön - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 citation: 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' 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.' 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.' 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.' mla: 'Parenti, Ilaria, et al. “Neurodevelopmental Disorders: From Genetics to Functional Pathways.” Trends in Neurosciences, vol. 43, no. 8, Elsevier, 2020, pp. 608–21, doi:10.1016/j.tins.2020.05.004.' short: I. Parenti, L.E. Garcia Rabaneda, H. Schön, G. Novarino, Trends in Neurosciences 43 (2020) 608–621. date_created: 2020-06-14T22:00:49Z date_published: 2020-08-01T00:00:00Z date_updated: 2023-08-21T08:25:31Z day: '01' ddc: - '570' department: - _id: GaNo doi: 10.1016/j.tins.2020.05.004 ec_funded: 1 external_id: isi: - '000553090600008' pmid: - '32507511' file: - access_level: open_access checksum: 67db0251b1d415ae59005f876fcf9e34 content_type: application/pdf creator: dernst date_created: 2020-11-25T09:43:40Z date_updated: 2020-11-25T09:43:40Z file_id: '8805' file_name: 2020_TrendsNeuroscience_Parenti.pdf file_size: 1439550 relation: main_file success: 1 file_date_updated: 2020-11-25T09:43:40Z has_accepted_license: '1' intvolume: ' 43' isi: 1 issue: '8' language: - iso: eng month: '08' oa: 1 oa_version: Published Version page: 608-621 pmid: 1 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 publication: Trends in Neurosciences publication_identifier: eissn: - 1878108X issn: - '01662236' publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: 'Neurodevelopmental disorders: From genetics to functional pathways' tmp: image: /images/cc_by.png legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0) short: CC BY (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 43 year: '2020' ... --- _id: '8131' abstract: - lang: eng text: The possibility to generate construct valid animal models enabled the development and testing of therapeutic strategies targeting the core features of autism spectrum disorders (ASDs). At the same time, these studies highlighted the necessity of identifying sensitive developmental time windows for successful therapeutic interventions. Animal and human studies also uncovered the possibility to stratify the variety of ASDs in molecularly distinct subgroups, potentially facilitating effective treatment design. Here, we focus on the molecular pathways emerging as commonly affected by mutations in diverse ASD-risk genes, on their role during critical windows of brain development and the potential treatments targeting these biological processes. article_processing_charge: Yes (via OA deal) article_type: original author: - first_name: Bernadette full_name: Basilico, Bernadette id: 36035796-5ACA-11E9-A75E-7AF2E5697425 last_name: Basilico orcid: 0000-0003-1843-3173 - first_name: Jasmin full_name: Morandell, Jasmin id: 4739D480-F248-11E8-B48F-1D18A9856A87 last_name: Morandell - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 citation: ama: Basilico B, Morandell J, Novarino G. Molecular mechanisms for targeted ASD treatments. Current Opinion in Genetics and Development. 2020;65(12):126-137. doi:10.1016/j.gde.2020.06.004 apa: Basilico, B., Morandell, J., & Novarino, G. (2020). Molecular mechanisms for targeted ASD treatments. Current Opinion in Genetics and Development. Elsevier. https://doi.org/10.1016/j.gde.2020.06.004 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. ieee: B. Basilico, J. Morandell, and G. Novarino, “Molecular mechanisms for targeted ASD treatments,” Current Opinion in Genetics and Development, vol. 65, no. 12. Elsevier, pp. 126–137, 2020. ista: Basilico B, Morandell J, Novarino G. 2020. Molecular mechanisms for targeted ASD treatments. Current Opinion in Genetics and Development. 65(12), 126–137. 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. short: B. Basilico, J. Morandell, G. Novarino, Current Opinion in Genetics and Development 65 (2020) 126–137. date_created: 2020-07-19T22:00:58Z date_published: 2020-12-01T00:00:00Z date_updated: 2024-09-10T12:04:25Z day: '01' ddc: - '570' department: - _id: GaNo doi: 10.1016/j.gde.2020.06.004 ec_funded: 1 external_id: isi: - '000598918900019' pmid: - '32659636' file: - access_level: open_access content_type: application/pdf creator: dernst date_created: 2020-07-22T06:47:45Z date_updated: 2020-07-22T06:47:45Z file_id: '8146' file_name: 2020_CurrentOpGenetics_Basilico.pdf file_size: 1381545 relation: main_file success: 1 file_date_updated: 2020-07-22T06:47:45Z has_accepted_license: '1' intvolume: ' 65' isi: 1 issue: '12' language: - iso: eng month: '12' oa: 1 oa_version: Published Version page: 126-137 pmid: 1 project: - _id: 260C2330-B435-11E9-9278-68D0E5697425 call_identifier: H2020 grant_number: '754411' name: ISTplus - Postdoctoral Fellowships - _id: 2548AE96-B435-11E9-9278-68D0E5697425 call_identifier: FWF grant_number: W1232-B24 name: Molecular Drug Targets - _id: 05A0D778-7A3F-11EA-A408-12923DDC885E grant_number: F07807 name: Neural stem cells in autism and epilepsy publication: Current Opinion in Genetics and Development publication_identifier: eissn: - '18790380' issn: - 0959437X publication_status: published publisher: Elsevier quality_controlled: '1' related_material: record: - id: '8620' relation: dissertation_contains status: public scopus_import: '1' status: public title: Molecular mechanisms for targeted ASD treatments tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 65 year: '2020' ... --- _id: '7586' abstract: - lang: eng 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. 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." article_number: e103358 article_processing_charge: No article_type: original author: - first_name: Stefanie full_name: Weinert, Stefanie last_name: Weinert - first_name: Niclas full_name: Gimber, Niclas last_name: Gimber - first_name: Dorothea full_name: Deuschel, Dorothea last_name: Deuschel - first_name: Till full_name: Stuhlmann, Till last_name: Stuhlmann - first_name: Dmytro full_name: Puchkov, Dmytro last_name: Puchkov - first_name: Zohreh full_name: Farsi, Zohreh last_name: Farsi - first_name: Carmen F. full_name: Ludwig, Carmen F. last_name: Ludwig - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 - first_name: Karen I. full_name: López-Cayuqueo, Karen I. last_name: López-Cayuqueo - first_name: Rosa full_name: Planells-Cases, Rosa last_name: Planells-Cases - first_name: Thomas J. full_name: Jentsch, Thomas J. last_name: Jentsch citation: 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 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. ieee: S. Weinert et al., “Uncoupling endosomal CLC chloride/proton exchange causes severe neurodegeneration,” EMBO Journal, vol. 39. EMBO Press, 2020. ista: Weinert S, Gimber N, Deuschel D, Stuhlmann T, Puchkov D, Farsi Z, Ludwig CF, Novarino G, López-Cayuqueo KI, Planells-Cases R, Jentsch TJ. 2020. Uncoupling endosomal CLC chloride/proton exchange causes severe neurodegeneration. EMBO Journal. 39, e103358. mla: Weinert, Stefanie, et al. “Uncoupling Endosomal CLC Chloride/Proton Exchange Causes Severe Neurodegeneration.” EMBO Journal, vol. 39, e103358, EMBO Press, 2020, doi:10.15252/embj.2019103358. short: S. Weinert, N. Gimber, D. Deuschel, T. Stuhlmann, D. Puchkov, Z. Farsi, C.F. Ludwig, G. Novarino, K.I. López-Cayuqueo, R. Planells-Cases, T.J. Jentsch, EMBO Journal 39 (2020). date_created: 2020-03-15T23:00:55Z date_published: 2020-03-02T00:00:00Z date_updated: 2023-08-18T07:07:36Z day: '02' ddc: - '570' department: - _id: GaNo doi: 10.15252/embj.2019103358 external_id: isi: - '000517335000001' pmid: - '32118314' file: - access_level: open_access checksum: 82750a7a93e3740decbce8474004111a content_type: application/pdf creator: dernst date_created: 2020-03-23T13:51:11Z date_updated: 2020-07-14T12:48:00Z file_id: '7615' file_name: 2020_EMBO_Weinert.pdf file_size: 12243278 relation: main_file file_date_updated: 2020-07-14T12:48:00Z has_accepted_license: '1' intvolume: ' 39' isi: 1 language: - iso: eng month: '03' oa: 1 oa_version: Published Version pmid: 1 publication: EMBO Journal publication_identifier: eissn: - '14602075' issn: - '02614189' publication_status: published publisher: EMBO Press quality_controlled: '1' scopus_import: '1' status: public title: Uncoupling endosomal CLC chloride/proton exchange causes severe neurodegeneration tmp: image: /images/cc_by_nc_nd.png legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) short: CC BY-NC-ND (4.0) type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 39 year: '2020' ... --- _id: '6896' abstract: - lang: eng text: "Until recently, a great amount of brain studies have been conducted in human post mortem tissues, cell lines and model organisms. These researches provided useful insights regarding cell-cell interactions occurring in the brain. However, such approaches suffer from technical limitations and inaccurate modeling of the tissue 3D cytoarchitecture. Importantly, they might lack a human genetic background essential for disease modeling. With the development of protocols to generate human cerebral organoids, we are now closer to reproducing the early stages of human brain development in vitro. As a result, more relevant cell-cell interaction studies can be conducted.\r\n\r\nIn this review, we discuss the advantages of 3D cultures over 2D in modulating brain cell-cell interactions during physiological and pathological development, as well as the progress made in developing organoids in which neurons, macroglia, microglia and vascularization are present. Finally, we debate the limitations of those models and possible future directions." article_number: '146458' article_processing_charge: No article_type: original author: - first_name: Bárbara full_name: Oliveira, Bárbara id: 3B03AA1A-F248-11E8-B48F-1D18A9856A87 last_name: Oliveira - first_name: Aysan Çerağ full_name: Yahya, Aysan Çerağ id: 365A65F8-F248-11E8-B48F-1D18A9856A87 last_name: Yahya - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 citation: 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 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. 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. ista: Oliveira B, Yahya AÇ, Novarino G. 2019. Modeling cell-cell interactions in the brain using cerebral organoids. Brain Research. 1724, 146458. mla: Oliveira, Bárbara, et al. “Modeling Cell-Cell Interactions in the Brain Using Cerebral Organoids.” Brain Research, vol. 1724, 146458, Elsevier, 2019, doi:10.1016/j.brainres.2019.146458. short: B. Oliveira, A.Ç. Yahya, G. Novarino, Brain Research 1724 (2019). date_created: 2019-09-22T22:00:35Z date_published: 2019-12-01T00:00:00Z date_updated: 2023-08-30T06:19:49Z day: '01' department: - _id: GaNo doi: 10.1016/j.brainres.2019.146458 external_id: isi: - '000491646600033' pmid: - '31521639' intvolume: ' 1724' isi: 1 language: - iso: eng month: '12' oa_version: None pmid: 1 publication: Brain Research publication_identifier: eissn: - '18726240' issn: - '00068993' publication_status: published publisher: Elsevier quality_controlled: '1' scopus_import: '1' status: public title: Modeling cell-cell interactions in the brain using cerebral organoids type: journal_article user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8 volume: 1724 year: '2019' ... --- _id: '7414' article_processing_charge: No article_type: original author: - first_name: Lisa full_name: Knaus, Lisa id: 3B2ABCF4-F248-11E8-B48F-1D18A9856A87 last_name: Knaus - first_name: Dora-Clara full_name: Tarlungeanu, Dora-Clara id: 2ABCE612-F248-11E8-B48F-1D18A9856A87 last_name: Tarlungeanu - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 citation: 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 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 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. 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. ista: Knaus L, Tarlungeanu D-C, Novarino G. 2019. S.16.03 A homozygous missense mutation in SLC7A5 leads to autism spectrum disorder and microcephaly. European Neuropsychopharmacology. 29(Supplement 6), S11. mla: Knaus, Lisa, et al. “S.16.03 A Homozygous Missense Mutation in SLC7A5 Leads to Autism Spectrum Disorder and Microcephaly.” 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. date_created: 2020-01-30T10:06:15Z date_published: 2019-12-13T00:00:00Z date_updated: 2023-09-07T14:55:23Z day: '13' department: - _id: GaNo doi: 10.1016/j.euroneuro.2019.09.039 external_id: isi: - '000502657500020' intvolume: ' 29' isi: 1 issue: Supplement 6 language: - iso: eng month: '12' oa_version: None page: S11 publication: European Neuropsychopharmacology publication_identifier: issn: - 0924-977X publication_status: published publisher: Elsevier quality_controlled: '1' status: public title: S.16.03 A homozygous missense mutation in SLC7A5 leads to autism spectrum disorder and microcephaly type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 29 year: '2019' ... --- _id: '7415' article_processing_charge: No article_type: original author: - first_name: Jasmin full_name: Morandell, Jasmin id: 4739D480-F248-11E8-B48F-1D18A9856A87 last_name: Morandell - first_name: Armel full_name: Nicolas, Armel id: 2A103192-F248-11E8-B48F-1D18A9856A87 last_name: Nicolas - first_name: Lena A full_name: Schwarz, Lena A id: 29A8453C-F248-11E8-B48F-1D18A9856A87 last_name: Schwarz - first_name: Gaia full_name: Novarino, Gaia id: 3E57A680-F248-11E8-B48F-1D18A9856A87 last_name: Novarino orcid: 0000-0002-7673-7178 citation: ama: Morandell J, Nicolas A, Schwarz LA, Novarino G. S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism. European Neuropsychopharmacology. 2019;29(Supplement 6):S11-S12. 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 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. 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. 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. mla: Morandell, Jasmin, et al. “S.16.05 Illuminating the Role of the E3 Ubiquitin Ligase Cullin3 in Brain Development and Autism.” European Neuropsychopharmacology, vol. 29, no. Supplement 6, Elsevier, 2019, pp. S11–12, doi:10.1016/j.euroneuro.2019.09.040. short: J. Morandell, A. Nicolas, L.A. Schwarz, G. Novarino, European Neuropsychopharmacology 29 (2019) S11–S12. date_created: 2020-01-30T10:07:41Z date_published: 2019-12-13T00:00:00Z date_updated: 2023-09-07T14:56:17Z day: '13' department: - _id: GaNo - _id: LifeSc doi: 10.1016/j.euroneuro.2019.09.040 external_id: isi: - '000502657500021' intvolume: ' 29' isi: 1 issue: Supplement 6 language: - iso: eng month: '12' oa_version: None page: S11-S12 publication: European Neuropsychopharmacology publication_identifier: issn: - 0924-977X publication_status: published publisher: Elsevier quality_controlled: '1' status: public title: S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism type: journal_article user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1 volume: 29 year: '2019' ...