[{"file":[{"checksum":"efc7edf9f626af31853790c5b598a68c","success":1,"date_created":"2023-01-30T10:25:21Z","date_updated":"2023-01-30T10:25:21Z","relation":"main_file","file_id":"12450","file_size":13588502,"content_type":"application/pdf","creator":"dernst","access_level":"open_access","file_name":"2022_FrontiersOntology_Basilico.pdf"}],"oa_version":"Published Version","_id":"12268","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","status":"public","ddc":["570"],"title":"Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells","intvolume":" 12","abstract":[{"text":"The complexity of the microenvironment effects on cell response, show accumulating evidence that glioblastoma (GBM) migration and invasiveness are influenced by the mechanical rigidity of their surroundings. The epithelial–mesenchymal transition (EMT) is a well-recognized driving force of the invasive behavior of cancer. However, the primary mechanisms of EMT initiation and progression remain unclear. We have previously showed that certain substrate stiffness can selectively stimulate human GBM U251-MG and GL15 glioblastoma cell lines motility. The present study unifies several known EMT mediators to uncover the reason of the regulation and response to these stiffnesses. Our results revealed that changing the rigidity of the mechanical environment tuned the response of both cell lines through change in morphological features, epithelial-mesenchymal markers (E-, N-Cadherin), EGFR and ROS expressions in an interrelated manner. Specifically, a stiffer microenvironment induced a mesenchymal cell shape, a more fragmented morphology, higher intracellular cytosolic ROS expression and lower mitochondrial ROS. Finally, we observed that cells more motile showed a more depolarized mitochondrial membrane potential. Unravelling the process that regulates GBM cells’ infiltrative behavior could provide new opportunities for identification of new targets and less invasive approaches for treatment.","lang":"eng"}],"type":"journal_article","date_published":"2022-08-25T00:00:00Z","publication":"Frontiers in Oncology","citation":{"ista":"Basilico B, Palamà IE, D’Amone S, Lauro C, Rosito M, Grieco M, Ratano P, Cordella F, Sanchini C, Di Angelantonio S, Ragozzino D, Cascione M, Gigli G, Cortese B. 2022. Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells. Frontiers in Oncology. 12, 983507.","apa":"Basilico, B., Palamà, I. E., D’Amone, S., Lauro, C., Rosito, M., Grieco, M., … Cortese, B. (2022). Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells. Frontiers in Oncology. Frontiers Media. https://doi.org/10.3389/fonc.2022.983507","ieee":"B. Basilico et al., “Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells,” Frontiers in Oncology, vol. 12. Frontiers Media, 2022.","ama":"Basilico B, Palamà IE, D’Amone S, et al. Substrate stiffness effect on molecular crosstalk of epithelial-mesenchymal transition mediators of human glioblastoma cells. Frontiers in Oncology. 2022;12. doi:10.3389/fonc.2022.983507","chicago":"Basilico, Bernadette, Ilaria Elena Palamà, Stefania D’Amone, Clotilde Lauro, Maria Rosito, Maddalena Grieco, Patrizia Ratano, et al. “Substrate Stiffness Effect on Molecular Crosstalk of Epithelial-Mesenchymal Transition Mediators of Human Glioblastoma Cells.” Frontiers in Oncology. Frontiers Media, 2022. https://doi.org/10.3389/fonc.2022.983507.","mla":"Basilico, Bernadette, et al. “Substrate Stiffness Effect on Molecular Crosstalk of Epithelial-Mesenchymal Transition Mediators of Human Glioblastoma Cells.” Frontiers in Oncology, vol. 12, 983507, Frontiers Media, 2022, doi:10.3389/fonc.2022.983507.","short":"B. Basilico, I.E. Palamà, S. D’Amone, C. Lauro, M. Rosito, M. Grieco, P. Ratano, F. Cordella, C. Sanchini, S. Di Angelantonio, D. Ragozzino, M. Cascione, G. Gigli, B. Cortese, Frontiers in Oncology 12 (2022)."},"article_type":"original","day":"25","article_processing_charge":"No","has_accepted_license":"1","scopus_import":"1","keyword":["Cancer Research","Oncology"],"author":[{"id":"36035796-5ACA-11E9-A75E-7AF2E5697425","orcid":"0000-0003-1843-3173","first_name":"Bernadette","last_name":"Basilico","full_name":"Basilico, Bernadette"},{"first_name":"Ilaria Elena","last_name":"Palamà","full_name":"Palamà, Ilaria Elena"},{"full_name":"D’Amone, Stefania","last_name":"D’Amone","first_name":"Stefania"},{"last_name":"Lauro","first_name":"Clotilde","full_name":"Lauro, Clotilde"},{"full_name":"Rosito, Maria","last_name":"Rosito","first_name":"Maria"},{"full_name":"Grieco, Maddalena","last_name":"Grieco","first_name":"Maddalena"},{"full_name":"Ratano, Patrizia","last_name":"Ratano","first_name":"Patrizia"},{"last_name":"Cordella","first_name":"Federica","full_name":"Cordella, Federica"},{"last_name":"Sanchini","first_name":"Caterina","full_name":"Sanchini, Caterina"},{"full_name":"Di Angelantonio, Silvia","first_name":"Silvia","last_name":"Di Angelantonio"},{"full_name":"Ragozzino, Davide","first_name":"Davide","last_name":"Ragozzino"},{"full_name":"Cascione, Mariafrancesca","first_name":"Mariafrancesca","last_name":"Cascione"},{"full_name":"Gigli, Giuseppe","first_name":"Giuseppe","last_name":"Gigli"},{"full_name":"Cortese, Barbara","first_name":"Barbara","last_name":"Cortese"}],"date_created":"2023-01-16T10:00:28Z","date_updated":"2023-08-04T09:54:16Z","volume":12,"acknowledgement":"The research leading to these results has received funding from AIRC under IG 2021 - ID. 26328 project – P.I. Cortese Barbara and AIRC under MFAG 2015 - ID. 16803 project – “P.I. Cortese Barbara”. The authors are also grateful to the ”Tecnopolo per la medicina di precisione” (TecnoMed Puglia) - Regione Puglia: DGR n.2117 del 21/11/2018, CUP: B84I18000540002 and “Tecnopolo di Nanotecnologia e Fotonica per la medicina di precisione” (TECNOMED) - FISR/MIUR-CNR: delibera CIPE n.3449 del 7-08-2017, CUP: B83B17000010001.\r\nWe thank Dr. Francesca Pagani for useful technical support. We thank also Irene Iacuitto, Giovanna Loffredo and Manuela Marchetti for practical administrative support.","year":"2022","pmid":1,"publication_status":"published","publisher":"Frontiers Media","department":[{"_id":"GaNo"}],"file_date_updated":"2023-01-30T10:25:21Z","article_number":"983507","doi":"10.3389/fonc.2022.983507","language":[{"iso":"eng"}],"external_id":{"isi":["000856524900001"],"pmid":["36091138"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"isi":1,"quality_controlled":"1","month":"08","publication_identifier":{"issn":["2234-943X"]}},{"publication":"Glia","citation":{"ista":"Basilico B, Ferrucci L, Ratano P, Golia MT, Grimaldi A, Rosito M, Ferretti V, Reverte I, Sanchini C, Marrone MC, Giubettini M, De Turris V, Salerno D, Garofalo S, St‐Pierre M, Carrier M, Renzi M, Pagani F, Modi B, Raspa M, Scavizzi F, Gross CT, Marinelli S, Tremblay M, Caprioli D, Maggi L, Limatola C, Di Angelantonio S, Ragozzino D. 2022. Microglia control glutamatergic synapses in the adult mouse hippocampus. Glia. 70(1), 173–195.","apa":"Basilico, B., Ferrucci, L., Ratano, P., Golia, M. T., Grimaldi, A., Rosito, M., … Ragozzino, D. (2022). Microglia control glutamatergic synapses in the adult mouse hippocampus. Glia. Wiley. https://doi.org/10.1002/glia.24101","ieee":"B. Basilico et al., “Microglia control glutamatergic synapses in the adult mouse hippocampus,” Glia, vol. 70, no. 1. Wiley, pp. 173–195, 2022.","ama":"Basilico B, Ferrucci L, Ratano P, et al. Microglia control glutamatergic synapses in the adult mouse hippocampus. Glia. 2022;70(1):173-195. doi:10.1002/glia.24101","chicago":"Basilico, Bernadette, Laura Ferrucci, Patrizia Ratano, Maria T. Golia, Alfonso Grimaldi, Maria Rosito, Valentina Ferretti, et al. “Microglia Control Glutamatergic Synapses in the Adult Mouse Hippocampus.” Glia. Wiley, 2022. https://doi.org/10.1002/glia.24101.","mla":"Basilico, Bernadette, et al. “Microglia Control Glutamatergic Synapses in the Adult Mouse Hippocampus.” Glia, vol. 70, no. 1, Wiley, 2022, pp. 173–95, doi:10.1002/glia.24101.","short":"B. Basilico, L. Ferrucci, P. Ratano, M.T. Golia, A. Grimaldi, M. Rosito, V. Ferretti, I. Reverte, C. Sanchini, M.C. Marrone, M. Giubettini, V. De Turris, D. Salerno, S. Garofalo, M. St‐Pierre, M. Carrier, M. Renzi, F. Pagani, B. Modi, M. Raspa, F. Scavizzi, C.T. Gross, S. Marinelli, M. Tremblay, D. Caprioli, L. Maggi, C. Limatola, S. Di Angelantonio, D. Ragozzino, Glia 70 (2022) 173–195."},"article_type":"original","page":"173-195","date_published":"2022-01-01T00:00:00Z","scopus_import":"1","keyword":["Cellular and Molecular Neuroscience","Neurology"],"day":"01","has_accepted_license":"1","article_processing_charge":"No","_id":"10818","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","ddc":["570"],"title":"Microglia control glutamatergic synapses in the adult mouse hippocampus","status":"public","intvolume":" 70","oa_version":"Published Version","file":[{"access_level":"open_access","file_name":"2021_Glia_Basilico.pdf","file_size":5340294,"content_type":"application/pdf","creator":"dernst","relation":"main_file","file_id":"10819","checksum":"f10a897290e66c0a062e04ba91db6c17","success":1,"date_updated":"2022-03-04T08:55:27Z","date_created":"2022-03-04T08:55:27Z"}],"type":"journal_article","abstract":[{"lang":"eng","text":"Microglia cells are active players in regulating synaptic development and plasticity in the brain. However, how they influence the normal functioning of synapses is largely unknown. In this study, we characterized the effects of pharmacological microglia depletion, achieved by administration of PLX5622, on hippocampal CA3-CA1 synapses of adult wild type mice. Following microglial depletion, we observed a reduction of spontaneous and evoked glutamatergic activity associated with a decrease of dendritic spine density. We also observed the appearance of immature synaptic features and higher levels of plasticity. Microglia depleted mice showed a deficit in the acquisition of the Novel Object Recognition task. These events were accompanied by hippocampal astrogliosis, although in the absence ofneuroinflammatory condition. PLX-induced synaptic changes were absent in Cx3cr1−/− mice, highlighting the role of CX3CL1/CX3CR1 axis in microglia control of synaptic functioning. Remarkably, microglia repopulation after PLX5622 withdrawal was associated with the recovery of hippocampal synapses and learning functions. Altogether, these data demonstrate that microglia contribute to normal synaptic functioning in the adult brain and that their removal induces reversible changes in organization and activity of glutamatergic synapses."}],"issue":"1","external_id":{"pmid":["34661306"],"isi":["000708025800001"]},"tmp":{"name":"Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc/4.0/legalcode","image":"/images/cc_by_nc.png","short":"CC BY-NC (4.0)"},"oa":1,"quality_controlled":"1","isi":1,"doi":"10.1002/glia.24101","language":[{"iso":"eng"}],"month":"01","publication_identifier":{"issn":["0894-1491"],"eissn":["1098-1136"]},"acknowledgement":"The work was supported by a grant from MIUR (PRIN 2017HPTFFC_003) to Davide Ragozzino and in part by funds to Silvia Di Angelantonio (CrestOptics-IIT JointLab for Advanced Microscopy) and Daniele Caprioli (Istituto Pasteur-Fondazione Cenci Bolognetti). Bernadette Basilico, and Laura Ferrucci were supported by the PhD program in Clinical-Experimental Neuroscience and Psychiatry, Sapienza University, Rome; Caterina Sanchini was supported by the PhD program in Life Science, Sapienza University, Rome and by the Italian Institute of Technology, Rome. The authors thank Alessandro Felici, Claudia Valeri, Arsenio Armagno, and Senthilkumar Deivasigamani for help with animal husbandry and transgenic colonies management. They also wish to thank Piotr Bregestovski and Michal Schwartz for helpful discussions and criticism. PLX5622 was provided under Materials Transfer Agreement by Plexxikon Inc. (Berkeley, CA). Open Access Funding provided by Universita degli Studi di Roma La Sapienza within the CRUI-CARE Agreement.","year":"2022","pmid":1,"publication_status":"published","department":[{"_id":"GaNo"}],"publisher":"Wiley","author":[{"full_name":"Basilico, Bernadette","first_name":"Bernadette","last_name":"Basilico","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","orcid":"0000-0003-1843-3173"},{"full_name":"Ferrucci, Laura","first_name":"Laura","last_name":"Ferrucci"},{"full_name":"Ratano, Patrizia","first_name":"Patrizia","last_name":"Ratano"},{"first_name":"Maria T.","last_name":"Golia","full_name":"Golia, Maria T."},{"last_name":"Grimaldi","first_name":"Alfonso","full_name":"Grimaldi, Alfonso"},{"full_name":"Rosito, Maria","first_name":"Maria","last_name":"Rosito"},{"full_name":"Ferretti, Valentina","first_name":"Valentina","last_name":"Ferretti"},{"first_name":"Ingrid","last_name":"Reverte","full_name":"Reverte, Ingrid"},{"first_name":"Caterina","last_name":"Sanchini","full_name":"Sanchini, Caterina"},{"first_name":"Maria C.","last_name":"Marrone","full_name":"Marrone, Maria C."},{"full_name":"Giubettini, Maria","first_name":"Maria","last_name":"Giubettini"},{"first_name":"Valeria","last_name":"De Turris","full_name":"De Turris, Valeria"},{"first_name":"Debora","last_name":"Salerno","full_name":"Salerno, Debora"},{"full_name":"Garofalo, Stefano","last_name":"Garofalo","first_name":"Stefano"},{"last_name":"St‐Pierre","first_name":"Marie‐Kim","full_name":"St‐Pierre, Marie‐Kim"},{"first_name":"Micael","last_name":"Carrier","full_name":"Carrier, Micael"},{"full_name":"Renzi, Massimiliano","last_name":"Renzi","first_name":"Massimiliano"},{"last_name":"Pagani","first_name":"Francesca","full_name":"Pagani, Francesca"},{"first_name":"Brijesh","last_name":"Modi","full_name":"Modi, Brijesh"},{"full_name":"Raspa, Marcello","last_name":"Raspa","first_name":"Marcello"},{"full_name":"Scavizzi, Ferdinando","first_name":"Ferdinando","last_name":"Scavizzi"},{"last_name":"Gross","first_name":"Cornelius T.","full_name":"Gross, Cornelius T."},{"full_name":"Marinelli, Silvia","first_name":"Silvia","last_name":"Marinelli"},{"first_name":"Marie‐Ève","last_name":"Tremblay","full_name":"Tremblay, Marie‐Ève"},{"full_name":"Caprioli, Daniele","first_name":"Daniele","last_name":"Caprioli"},{"full_name":"Maggi, Laura","first_name":"Laura","last_name":"Maggi"},{"first_name":"Cristina","last_name":"Limatola","full_name":"Limatola, Cristina"},{"full_name":"Di Angelantonio, Silvia","first_name":"Silvia","last_name":"Di Angelantonio"},{"full_name":"Ragozzino, Davide","last_name":"Ragozzino","first_name":"Davide"}],"date_created":"2022-03-04T08:53:37Z","date_updated":"2023-09-05T16:01:23Z","volume":70,"file_date_updated":"2022-03-04T08:55:27Z"},{"type":"preprint","abstract":[{"lang":"eng","text":"Complex wiring between neurons underlies the information-processing network enabling all brain functions, including cognition and memory. For understanding how the network is structured, processes information, and changes over time, comprehensive visualization of the architecture of living brain tissue with its cellular and molecular components would open up major opportunities. However, electron microscopy (EM) provides nanometre-scale resolution required for full in-silico reconstruction1–5, yet is limited to fixed specimens and static representations. Light microscopy allows live observation, with super-resolution approaches6–12 facilitating nanoscale visualization, but comprehensive 3D-reconstruction of living brain tissue has been hindered by tissue photo-burden, photobleaching, insufficient 3D-resolution, and inadequate signal-to-noise ratio (SNR). Here we demonstrate saturated reconstruction of living brain tissue. We developed an integrated imaging and analysis technology, adapting stimulated emission depletion (STED) microscopy6,13 in extracellularly labelled tissue14 for high SNR and near-isotropic resolution. Centrally, a two-stage deep-learning approach leveraged previously obtained information on sample structure to drastically reduce photo-burden and enable automated volumetric reconstruction down to single synapse level. Live reconstruction provides unbiased analysis of tissue architecture across time in relation to functional activity and targeted activation, and contextual understanding of molecular labelling. This adoptable technology will facilitate novel insights into the dynamic functional architecture of living brain tissue."}],"_id":"11943","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","year":"2022","department":[{"_id":"PeJo"},{"_id":"GaNo"},{"_id":"BeBi"},{"_id":"JoDa"}],"publisher":"Cold Spring Harbor Laboratory","status":"public","publication_status":"submitted","title":"Saturated reconstruction of living brain tissue","related_material":{"record":[{"id":"12470","relation":"dissertation_contains","status":"public"}]},"author":[{"last_name":"Velicky","first_name":"Philipp","orcid":"0000-0002-2340-7431","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","full_name":"Velicky, Philipp"},{"full_name":"Miguel Villalba, Eder","orcid":"0000-0001-5665-0430","id":"3FB91342-F248-11E8-B48F-1D18A9856A87","last_name":"Miguel Villalba","first_name":"Eder"},{"full_name":"Michalska, Julia M","first_name":"Julia M","last_name":"Michalska","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-3862-1235"},{"first_name":"Donglai","last_name":"Wei","full_name":"Wei, Donglai"},{"first_name":"Zudi","last_name":"Lin","full_name":"Lin, Zudi"},{"last_name":"Watson","first_name":"Jake","orcid":"0000-0002-8698-3823","id":"63836096-4690-11EA-BD4E-32803DDC885E","full_name":"Watson, Jake"},{"first_name":"Jakob","last_name":"Troidl","full_name":"Troidl, Jakob"},{"first_name":"Johanna","last_name":"Beyer","full_name":"Beyer, Johanna"},{"full_name":"Ben Simon, Yoav","first_name":"Yoav","last_name":"Ben Simon","id":"43DF3136-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Sommer, Christoph M","first_name":"Christoph M","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105"},{"last_name":"Jahr","first_name":"Wiebke","id":"425C1CE8-F248-11E8-B48F-1D18A9856A87","full_name":"Jahr, Wiebke"},{"id":"9ac8f577-2357-11eb-997a-e566c5550886","first_name":"Alban","last_name":"Cenameri","full_name":"Cenameri, Alban"},{"last_name":"Broichhagen","first_name":"Johannes","full_name":"Broichhagen, Johannes"},{"last_name":"Grant","first_name":"Seth G. N.","full_name":"Grant, Seth G. N."},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","first_name":"Peter M","last_name":"Jonas","full_name":"Jonas, Peter M"},{"orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia","full_name":"Novarino, Gaia"},{"full_name":"Pfister, Hanspeter","last_name":"Pfister","first_name":"Hanspeter"},{"full_name":"Bickel, Bernd","orcid":"0000-0001-6511-9385","id":"49876194-F248-11E8-B48F-1D18A9856A87","last_name":"Bickel","first_name":"Bernd"},{"orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","last_name":"Danzl","first_name":"Johann G","full_name":"Danzl, Johann G"}],"oa_version":"Preprint","date_updated":"2024-03-28T23:30:20Z","date_created":"2022-08-23T11:07:59Z","article_processing_charge":"No","month":"05","day":"09","oa":1,"citation":{"short":"P. Velicky, E. Miguel Villalba, J.M. Michalska, D. Wei, Z. Lin, J. Watson, J. Troidl, J. Beyer, Y. Ben Simon, C.M. Sommer, W. Jahr, A. Cenameri, J. Broichhagen, S.G.N. Grant, P.M. Jonas, G. Novarino, H. Pfister, B. Bickel, J.G. Danzl, BioRxiv (n.d.).","mla":"Velicky, Philipp, et al. “Saturated Reconstruction of Living Brain Tissue.” BioRxiv, Cold Spring Harbor Laboratory, doi: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.","ama":"Velicky P, Miguel Villalba E, Michalska JM, et al. Saturated reconstruction of living brain tissue. bioRxiv. doi:10.1101/2022.03.16.484431","ieee":"P. Velicky et al., “Saturated reconstruction of living brain tissue,” bioRxiv. Cold Spring Harbor Laboratory.","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","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."},"main_file_link":[{"url":"https://doi.org/10.1101/2022.03.16.484431","open_access":"1"}],"publication":"bioRxiv","date_published":"2022-05-09T00:00:00Z","doi":"10.1101/2022.03.16.484431","language":[{"iso":"eng"}]},{"publication":"bioRxiv","oa":1,"main_file_link":[{"url":"https://doi.org/10.1101/2022.08.17.504272","open_access":"1"}],"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","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.","short":"J.M. Michalska, J. Lyudchik, P. Velicky, H. Korinkova, J. Watson, A. Cenameri, C.M. Sommer, A. Venturino, K. Roessler, T. Czech, S. Siegert, G. Novarino, P.M. Jonas, J.G. Danzl, BioRxiv (n.d.).","mla":"Michalska, Julia M., et al. “Uncovering Brain Tissue Architecture across Scales with Super-Resolution Light Microscopy.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2022.08.17.504272.","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."},"doi":"10.1101/2022.08.17.504272","date_published":"2022-08-18T00:00:00Z","language":[{"iso":"eng"}],"month":"08","day":"18","article_processing_charge":"No","year":"2022","_id":"11950","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","publication_status":"submitted","title":"Uncovering brain tissue architecture across scales with super-resolution light microscopy","status":"public","department":[{"_id":"SaSi"},{"_id":"GaNo"},{"_id":"PeJo"},{"_id":"JoDa"}],"publisher":"Cold Spring Harbor Laboratory","author":[{"full_name":"Michalska, Julia M","orcid":"0000-0003-3862-1235","id":"443DB6DE-F248-11E8-B48F-1D18A9856A87","last_name":"Michalska","first_name":"Julia M"},{"id":"46E28B80-F248-11E8-B48F-1D18A9856A87","last_name":"Lyudchik","first_name":"Julia","full_name":"Lyudchik, Julia"},{"orcid":"0000-0002-2340-7431","id":"39BDC62C-F248-11E8-B48F-1D18A9856A87","last_name":"Velicky","first_name":"Philipp","full_name":"Velicky, Philipp"},{"full_name":"Korinkova, Hana","first_name":"Hana","last_name":"Korinkova","id":"ee3cb6ca-ec98-11ea-ae11-ff703e2254ed"},{"orcid":"0000-0002-8698-3823","id":"63836096-4690-11EA-BD4E-32803DDC885E","last_name":"Watson","first_name":"Jake","full_name":"Watson, Jake"},{"last_name":"Cenameri","first_name":"Alban","id":"9ac8f577-2357-11eb-997a-e566c5550886","full_name":"Cenameri, Alban"},{"full_name":"Sommer, Christoph M","first_name":"Christoph M","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105"},{"id":"41CB84B2-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-2356-9403","first_name":"Alessandro","last_name":"Venturino","full_name":"Venturino, Alessandro"},{"first_name":"Karl","last_name":"Roessler","full_name":"Roessler, Karl"},{"full_name":"Czech, Thomas","first_name":"Thomas","last_name":"Czech"},{"orcid":"0000-0001-8635-0877","id":"36ACD32E-F248-11E8-B48F-1D18A9856A87","last_name":"Siegert","first_name":"Sandra","full_name":"Siegert, Sandra"},{"full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino"},{"id":"353C1B58-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-5001-4804","first_name":"Peter M","last_name":"Jonas","full_name":"Jonas, Peter M"},{"full_name":"Danzl, Johann G","first_name":"Johann G","last_name":"Danzl","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973"}],"related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"12470"}]},"date_updated":"2024-03-28T23:30:20Z","date_created":"2022-08-24T08:24:52Z","oa_version":"Preprint","type":"preprint","abstract":[{"text":"Mapping the complex and dense arrangement of cells and their connectivity in brain tissue demands nanoscale spatial resolution imaging. Super-resolution optical microscopy excels at visualizing specific molecules and individual cells but fails to provide tissue context. Here we developed Comprehensive Analysis of Tissues across Scales (CATS), a technology to densely map brain tissue architecture from millimeter regional to nanoscopic synaptic scales in diverse chemically fixed brain preparations, including rodent and human. CATS leverages fixation-compatible extracellular labeling and advanced optical readout, in particular stimulated-emission depletion and expansion microscopy, to comprehensively delineate cellular structures. It enables 3D-reconstructing single synapses and mapping synaptic connectivity by identification and tailored analysis of putative synaptic cleft regions. Applying CATS to the hippocampal mossy fiber circuitry, we demonstrate its power to reveal the system’s molecularly informed ultrastructure across spatial scales and assess local connectivity by reconstructing and quantifying the synaptic input and output structure of identified neurons.","lang":"eng"}]},{"type":"journal_article","abstract":[{"text":"Mutations in the chromodomain helicase DNA-binding 8 (CHD8) gene are a frequent cause of autism spectrum disorder (ASD). While its phenotypic spectrum often encompasses macrocephaly, implicating cortical abnormalities, how CHD8 haploinsufficiency affects neurodevelopmental is unclear. Here, employing human cerebral organoids, we find that CHD8 haploinsufficiency disrupted neurodevelopmental trajectories with an accelerated and delayed generation of, respectively, inhibitory and excitatory neurons that yields, at days 60 and 120, symmetrically opposite expansions in their proportions. This imbalance is consistent with an enlargement of cerebral organoids as an in vitro correlate of patients’ macrocephaly. Through an isogenic design of patient-specific mutations and mosaic organoids, we define genotype-phenotype relationships and uncover their cell-autonomous nature. Our results define cell-type-specific CHD8-dependent molecular defects related to an abnormal program of proliferation and alternative splicing. By identifying cell-type-specific effects of CHD8 mutations, our study uncovers reproducible developmental alterations that may be employed for neurodevelopmental disease modeling.","lang":"eng"}],"issue":"1","_id":"11160","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","title":"CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories","ddc":["570"],"status":"public","intvolume":" 39","oa_version":"Published Version","file":[{"file_id":"11164","relation":"main_file","success":1,"checksum":"b4e8d68f0268dec499af333e6fd5d8e1","date_created":"2022-04-15T09:06:25Z","date_updated":"2022-04-15T09:06:25Z","access_level":"open_access","file_name":"2022_CellReports_Villa.pdf","creator":"dernst","content_type":"application/pdf","file_size":"7808644"}],"keyword":["General Biochemistry","Genetics and Molecular Biology"],"day":"05","article_processing_charge":"Yes","has_accepted_license":"1","publication":"Cell Reports","citation":{"mla":"Villa, Carlo Emanuele, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” Cell Reports, vol. 39, no. 1, 110615, Elsevier, 2022, doi:10.1016/j.celrep.2022.110615.","short":"C.E. Villa, C. Cheroni, C. Dotter, A. López-Tóbon, B. Oliveira, R. Sacco, A.Ç. Yahya, J. Morandell, M. Gabriele, M. Tavakoli, J. Lyudchik, C.M. Sommer, M. Gabitto, J.G. Danzl, G. Testa, G. Novarino, Cell Reports 39 (2022).","chicago":"Villa, Carlo Emanuele, Cristina Cheroni, Christoph Dotter, Alejandro López-Tóbon, Bárbara Oliveira, Roberto Sacco, Aysan Çerağ Yahya, et al. “CHD8 Haploinsufficiency Links Autism to Transient Alterations in Excitatory and Inhibitory Trajectories.” Cell Reports. Elsevier, 2022. https://doi.org/10.1016/j.celrep.2022.110615.","ama":"Villa CE, Cheroni C, Dotter C, et al. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. Cell Reports. 2022;39(1). doi:10.1016/j.celrep.2022.110615","ista":"Villa CE, Cheroni C, Dotter C, López-Tóbon A, Oliveira B, Sacco R, Yahya AÇ, Morandell J, Gabriele M, Tavakoli M, Lyudchik J, Sommer CM, Gabitto M, Danzl JG, Testa G, Novarino G. 2022. CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. Cell Reports. 39(1), 110615.","apa":"Villa, C. E., Cheroni, C., Dotter, C., López-Tóbon, A., Oliveira, B., Sacco, R., … Novarino, G. (2022). CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories. Cell Reports. Elsevier. https://doi.org/10.1016/j.celrep.2022.110615","ieee":"C. E. Villa et al., “CHD8 haploinsufficiency links autism to transient alterations in excitatory and inhibitory trajectories,” Cell Reports, vol. 39, no. 1. Elsevier, 2022."},"article_type":"original","date_published":"2022-04-05T00:00:00Z","article_number":"110615","file_date_updated":"2022-04-15T09:06:25Z","ec_funded":1,"year":"2022","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.","pmid":1,"publication_status":"published","department":[{"_id":"JoDa"},{"_id":"GaNo"}],"publisher":"Elsevier","author":[{"last_name":"Villa","first_name":"Carlo Emanuele","full_name":"Villa, Carlo Emanuele"},{"first_name":"Cristina","last_name":"Cheroni","full_name":"Cheroni, Cristina"},{"full_name":"Dotter, Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9033-9096","first_name":"Christoph","last_name":"Dotter"},{"full_name":"López-Tóbon, Alejandro","first_name":"Alejandro","last_name":"López-Tóbon"},{"last_name":"Oliveira","first_name":"Bárbara","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","full_name":"Oliveira, Bárbara"},{"id":"42C9F57E-F248-11E8-B48F-1D18A9856A87","last_name":"Sacco","first_name":"Roberto","full_name":"Sacco, Roberto"},{"id":"365A65F8-F248-11E8-B48F-1D18A9856A87","first_name":"Aysan Çerağ","last_name":"Yahya","full_name":"Yahya, Aysan Çerağ"},{"id":"4739D480-F248-11E8-B48F-1D18A9856A87","first_name":"Jasmin","last_name":"Morandell","full_name":"Morandell, Jasmin"},{"full_name":"Gabriele, Michele","last_name":"Gabriele","first_name":"Michele"},{"full_name":"Tavakoli, Mojtaba","last_name":"Tavakoli","first_name":"Mojtaba","orcid":"0000-0002-7667-6854","id":"3A0A06F4-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Lyudchik, Julia","last_name":"Lyudchik","first_name":"Julia","id":"46E28B80-F248-11E8-B48F-1D18A9856A87"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","first_name":"Christoph M","last_name":"Sommer","full_name":"Sommer, Christoph M"},{"full_name":"Gabitto, Mariano","first_name":"Mariano","last_name":"Gabitto"},{"id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8559-3973","first_name":"Johann G","last_name":"Danzl","full_name":"Danzl, Johann G"},{"full_name":"Testa, Giuseppe","last_name":"Testa","first_name":"Giuseppe"},{"first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"}],"related_material":{"record":[{"id":"12364","relation":"dissertation_contains","status":"public"}]},"date_updated":"2024-03-28T23:30:45Z","date_created":"2022-04-15T09:03:10Z","volume":39,"month":"04","publication_identifier":{"issn":["2211-1247"]},"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"pmid":["35385734"],"isi":["000785983900003"]},"quality_controlled":"1","isi":1,"project":[{"call_identifier":"H2020","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","grant_number":"715508","_id":"25444568-B435-11E9-9278-68D0E5697425"},{"grant_number":"I04205","_id":"2690FEAC-B435-11E9-9278-68D0E5697425","name":"Identification of converging Molecular Pathways Across Chromatinopathies as Targets for Therapy","call_identifier":"FWF"}],"doi":"10.1016/j.celrep.2022.110615","acknowledged_ssus":[{"_id":"Bio"},{"_id":"LifeSc"}],"language":[{"iso":"eng"}]},{"alternative_title":["ISTA Thesis"],"type":"dissertation","abstract":[{"lang":"eng","text":"Autism spectrum disorders (ASDs) are a group of neurodevelopmental disorders character\u0002ized by behavioral symptoms such as problems in social communication and interaction, as\r\nwell as repetitive, restricted behaviors and interests. These disorders show a high degree\r\nof heritability and hundreds of risk genes have been identifed using high throughput\r\nsequencing technologies. This genetic heterogeneity has hampered eforts in understanding\r\nthe pathogenesis of ASD but at the same time given rise to the concept of convergent\r\nmechanisms. Previous studies have identifed that risk genes for ASD broadly converge\r\nonto specifc functional categories with transcriptional regulation being one of the biggest\r\ngroups. In this thesis, I focus on this subgroup of genes and investigate the gene regulatory\r\nconsequences of some of them in the context of neurodevelopment.\r\nFirst, we showed that mutations in the ASD and intellectual disability risk gene Setd5 lead\r\nto perturbations of gene regulatory programs in early cell fate specifcation. In addition,\r\nadult animals display abnormal learning behavior which is mirrored at the transcriptional\r\nlevel by altered activity dependent regulation of postsynaptic gene expression. Lastly,\r\nwe link the regulatory function of Setd5 to its interaction with the Paf1 and the NCoR\r\ncomplex.\r\nSecond, by modeling the heterozygous loss of the top ASD gene CHD8 in human cerebral\r\norganoids we demonstrate profound changes in the developmental trajectories of both\r\ninhibitory and excitatory neurons using single cell RNA-sequencing. While the former\r\nwere generated earlier in CHD8+/- organoids, the generation of the latter was shifted to\r\nlater times in favor of a prolonged progenitor expansion phase and ultimately increased\r\norganoid size.\r\nFinally, by modeling heterozygous mutations for four ASD associated chromatin modifers,\r\nASH1L, KDM6B, KMT5B, and SETD5 in human cortical spheroids we show evidence of\r\nregulatory convergence across three of those genes. We observe a shift from dorsal cortical\r\nexcitatory neuron fates towards partially ventralized cell types resembling cells from the\r\nlateral ganglionic eminence. As this project is still ongoing at the time of writing, future\r\nexperiments will aim at elucidating the regulatory mechanisms underlying this shift with\r\nthe aim of linking these three ASD risk genes through biological convergence."}],"ddc":["570"],"title":"Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder","status":"public","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","_id":"12364","file":[{"access_level":"open_access","file_name":"220923_Thesis_CDotter_Final.pdf","creator":"cchlebak","file_size":20457465,"content_type":"application/pdf","embargo":"2023-09-19","file_id":"12365","relation":"main_file","checksum":"896f4cac9adb6d3f26a6605772f4e1a3","date_created":"2023-01-24T13:15:45Z","date_updated":"2023-09-20T22:30:03Z"},{"creator":"cchlebak","content_type":"application/x-zip-compressed","file_size":22433512,"access_level":"closed","file_name":"latex_source_CDotter_Thesis_2022.zip","embargo_to":"open_access","checksum":"ad01bb20da163be6893b7af832e58419","date_created":"2023-02-02T09:15:35Z","date_updated":"2023-09-20T22:30:03Z","file_id":"12482","relation":"source_file"}],"oa_version":"Published Version","article_processing_charge":"No","has_accepted_license":"1","day":"19","page":"152","citation":{"chicago":"Dotter, Christoph. “Transcriptional Consequences of Mutations in Genes Associated with Autism Spectrum Disorder.” Institute of Science and Technology Austria, 2022. https://doi.org/10.15479/at:ista:12094.","short":"C. Dotter, Transcriptional Consequences of Mutations in Genes Associated with Autism Spectrum Disorder, Institute of Science and Technology Austria, 2022.","mla":"Dotter, Christoph. Transcriptional Consequences of Mutations in Genes Associated with Autism Spectrum Disorder. Institute of Science and Technology Austria, 2022, doi:10.15479/at:ista:12094.","ieee":"C. Dotter, “Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder,” Institute of Science and Technology Austria, 2022.","apa":"Dotter, C. (2022). Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:12094","ista":"Dotter C. 2022. Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder. Institute of Science and Technology Austria.","ama":"Dotter C. Transcriptional consequences of mutations in genes associated with Autism Spectrum Disorder. 2022. doi:10.15479/at:ista:12094"},"date_published":"2022-09-19T00:00:00Z","ec_funded":1,"file_date_updated":"2023-09-20T22:30:03Z","publisher":"Institute of Science and Technology Austria","department":[{"_id":"GradSch"},{"_id":"GaNo"}],"publication_status":"published","year":"2022","date_created":"2023-01-24T13:09:57Z","date_updated":"2023-11-16T13:10:22Z","related_material":{"record":[{"id":"3","status":"public","relation":"part_of_dissertation"},{"id":"11160","relation":"part_of_dissertation","status":"public"}]},"author":[{"last_name":"Dotter","first_name":"Christoph","orcid":"0000-0002-9033-9096","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","full_name":"Dotter, Christoph"}],"publication_identifier":{"issn":["2663-337X"]},"month":"09","project":[{"name":"Probing development and reversibility of autism spectrum disorders","grant_number":"401299","_id":"254BA948-B435-11E9-9278-68D0E5697425"},{"name":"Critical windows and reversibility of ASD associated with mutations in chromatin remodelers","_id":"9B91375C-BA93-11EA-9121-9846C619BF3A","grant_number":"707964"},{"call_identifier":"H2020","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","_id":"25444568-B435-11E9-9278-68D0E5697425","grant_number":"715508"},{"name":"Identification of converging Molecular Pathways Across Chromatinopathies as Targets for Therapy","call_identifier":"FWF","grant_number":"I04205","_id":"2690FEAC-B435-11E9-9278-68D0E5697425"}],"oa":1,"language":[{"iso":"eng"}],"supervisor":[{"full_name":"Novarino, Gaia","first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178"}],"degree_awarded":"PhD","doi":"10.15479/at:ista:12094"},{"file":[{"date_created":"2022-05-16T07:02:27Z","date_updated":"2022-05-16T07:02:27Z","success":1,"checksum":"256cb832a9c3051c7dc741f6423b8cbd","file_id":"11380","relation":"main_file","creator":"dernst","file_size":1335308,"content_type":"application/pdf","file_name":"2021_Genes_Vasic.pdf","access_level":"open_access"}],"oa_version":"Published Version","title":"Translating the role of mtor-and ras-associated signalopathies in autism spectrum disorder: Models, mechanisms and treatment","ddc":["570"],"status":"public","intvolume":" 12","_id":"10281","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","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"}],"issue":"11","alternative_title":["Special Issue \"From Genes to Therapy in Autism Spectrum Disorder\""],"type":"journal_article","date_published":"2021-10-30T00:00:00Z","article_type":"original","publication":"Genes","citation":{"short":"V. Vasic, M.S.O. Jones, D. Haslinger, L. Knaus, M.J. Schmeisser, G. Novarino, A.G. Chiocchetti, Genes 12 (2021).","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.","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.","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","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."},"day":"30","has_accepted_license":"1","article_processing_charge":"No","scopus_import":"1","date_updated":"2023-08-14T11:46:12Z","date_created":"2021-11-14T23:01:24Z","volume":12,"author":[{"last_name":"Vasic","first_name":"Verica","full_name":"Vasic, Verica"},{"last_name":"Jones","first_name":"Mattson S.O.","full_name":"Jones, Mattson S.O."},{"full_name":"Haslinger, Denise","id":"76922BDA-3D3B-11EA-90BD-A44F3DDC885E","last_name":"Haslinger","first_name":"Denise"},{"first_name":"Lisa","last_name":"Knaus","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","full_name":"Knaus, Lisa"},{"last_name":"Schmeisser","first_name":"Michael J.","full_name":"Schmeisser, Michael J."},{"full_name":"Novarino, Gaia","last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Andreas G.","last_name":"Chiocchetti","full_name":"Chiocchetti, Andreas G."}],"publication_status":"published","publisher":"MDPI","department":[{"_id":"GaNo"}],"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.","year":"2021","file_date_updated":"2022-05-16T07:02:27Z","ec_funded":1,"article_number":"1746","language":[{"iso":"eng"}],"doi":"10.3390/genes12111746","isi":1,"quality_controlled":"1","project":[{"name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020","grant_number":"715508","_id":"25444568-B435-11E9-9278-68D0E5697425"},{"name":"Molecular Drug Targets","call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24"}],"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000834044200002"]},"month":"10","publication_identifier":{"eissn":["2073-4425"]}},{"keyword":["general immunology and microbiology","general biochemistry","genetics and molecular biology","general medicine","general neuroscience"],"day":"17","has_accepted_license":"1","article_processing_charge":"No","publication":"eLife","citation":{"mla":"Conde-Dusman, María J., et al. “Control of Protein Synthesis and Memory by GluN3A-NMDA Receptors through Inhibition of GIT1/MTORC1 Assembly.” ELife, vol. 10, e71575, eLife Sciences Publications, 2021, doi:10.7554/elife.71575.","short":"M.J. Conde-Dusman, P.N. Dey, Ó. Elía-Zudaire, L.E. Garcia Rabaneda, C. García-Lira, T. Grand, V. Briz, E.R. Velasco, R. Andero Galí, S. Niñerola, A. Barco, P. Paoletti, J.F. Wesseling, F. Gardoni, S.J. Tavalin, I. Perez-Otaño, ELife 10 (2021).","chicago":"Conde-Dusman, María J, Partha N Dey, Óscar Elía-Zudaire, Luis E Garcia Rabaneda, Carmen García-Lira, Teddy Grand, Victor Briz, et al. “Control of Protein Synthesis and Memory by GluN3A-NMDA Receptors through Inhibition of GIT1/MTORC1 Assembly.” ELife. eLife Sciences Publications, 2021. https://doi.org/10.7554/elife.71575.","ama":"Conde-Dusman MJ, Dey PN, Elía-Zudaire Ó, et al. Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly. eLife. 2021;10. doi:10.7554/elife.71575","ista":"Conde-Dusman MJ, Dey PN, Elía-Zudaire Ó, Garcia Rabaneda LE, García-Lira C, Grand T, Briz V, Velasco ER, Andero Galí R, Niñerola S, Barco A, Paoletti P, Wesseling JF, Gardoni F, Tavalin SJ, Perez-Otaño I. 2021. Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly. eLife. 10, e71575.","ieee":"M. J. Conde-Dusman et al., “Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly,” eLife, vol. 10. eLife Sciences Publications, 2021.","apa":"Conde-Dusman, M. J., Dey, P. N., Elía-Zudaire, Ó., Garcia Rabaneda, L. E., García-Lira, C., Grand, T., … Perez-Otaño, I. (2021). Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.71575"},"article_type":"original","date_published":"2021-11-17T00:00:00Z","type":"journal_article","abstract":[{"lang":"eng","text":"De novo protein synthesis is required for synapse modifications underlying stable memory encoding. Yet neurons are highly compartmentalized cells and how protein synthesis can be regulated at the synapse level is unknown. Here, we characterize neuronal signaling complexes formed by the postsynaptic scaffold GIT1, the mechanistic target of rapamycin (mTOR) kinase, and Raptor that couple synaptic stimuli to mTOR-dependent protein synthesis; and identify NMDA receptors containing GluN3A subunits as key negative regulators of GIT1 binding to mTOR. Disruption of GIT1/mTOR complexes by enhancing GluN3A expression or silencing GIT1 inhibits synaptic mTOR activation and restricts the mTOR-dependent translation of specific activity-regulated mRNAs. Conversely, GluN3A removal enables complex formation, potentiates mTOR-dependent protein synthesis, and facilitates the consolidation of associative and spatial memories in mice. The memory enhancement becomes evident with light or spaced training, can be achieved by selectively deleting GluN3A from excitatory neurons during adulthood, and does not compromise other aspects of cognition such as memory flexibility or extinction. Our findings provide mechanistic insight into synaptic translational control and reveal a potentially selective target for cognitive enhancement."}],"_id":"10301","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","ddc":["570"],"status":"public","title":"Control of protein synthesis and memory by GluN3A-NMDA receptors through inhibition of GIT1/mTORC1 assembly","intvolume":" 10","file":[{"date_created":"2021-11-18T07:02:02Z","date_updated":"2021-11-18T07:02:02Z","checksum":"59318e9e41507cec83c2f4070e6ad540","success":1,"relation":"main_file","file_id":"10302","file_size":2477302,"content_type":"application/pdf","creator":"lgarciar","file_name":"elife-71575-v1.pdf","access_level":"open_access"}],"oa_version":"Published Version","month":"11","publication_identifier":{"issn":["2050-084X"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"external_id":{"isi":["000720945900001"]},"isi":1,"quality_controlled":"1","doi":"10.7554/elife.71575","language":[{"iso":"eng"}],"article_number":"e71575","file_date_updated":"2021-11-18T07:02:02Z","acknowledgement":"We thank Stuart Lipton and Nobuki Nakanishi for providing the Grin3a knockout mice, Beverly Davidson for the AAV-caRheb, Jose Esteban for help with behavioral and biochemical experiments, and Noelia Campillo, Rebeca Martínez-Turrillas, and Ana Navarro for expert technical help. Work was funded by the UTE project CIMA; fellowships from the Fundación Tatiana Pérez de Guzmán el Bueno, FEBS, and IBRO (to M.J.C.D.), Generalitat Valenciana (to O.E.-Z.), Juan de la Cierva (to L.G.R.), FPI-MINECO (to E.R.V., to S.N.) and Intertalentum postdoctoral program (to V.B.); ANR (GluBrain3A) and ERC Advanced Grants (#693021) (to P.P.); Ramón y Cajal program RYC2014-15784, RETOS-MINECO SAF2016-76565-R, ERANET-Neuron JTC 2019 ISCIII AC19/00077 FEDER funds (to R.A.); RETOS-MINECO SAF2017-87928-R (to A.B.); an NIH grant (NS76637) and UTHSC College of Medicine funds (to S.J.T.); and NARSAD Independent Investigator Award and grants from the MINECO (CSD2008-00005, SAF2013-48983R, SAF2016-80895-R), Generalitat Valenciana (PROMETEO 2019/020)(to I.P.O.) and Severo-Ochoa Excellence Awards (SEV-2013-0317, SEV-2017-0723).","year":"2021","publication_status":"published","publisher":"eLife Sciences Publications","department":[{"_id":"GaNo"}],"author":[{"first_name":"María J","last_name":"Conde-Dusman","full_name":"Conde-Dusman, María J"},{"full_name":"Dey, Partha N","first_name":"Partha N","last_name":"Dey"},{"full_name":"Elía-Zudaire, Óscar","last_name":"Elía-Zudaire","first_name":"Óscar"},{"id":"33D1B084-F248-11E8-B48F-1D18A9856A87","first_name":"Luis E","last_name":"Garcia Rabaneda","full_name":"Garcia Rabaneda, Luis E"},{"full_name":"García-Lira, Carmen","last_name":"García-Lira","first_name":"Carmen"},{"first_name":"Teddy","last_name":"Grand","full_name":"Grand, Teddy"},{"last_name":"Briz","first_name":"Victor","full_name":"Briz, Victor"},{"last_name":"Velasco","first_name":"Eric R","full_name":"Velasco, Eric R"},{"first_name":"Raül","last_name":"Andero Galí","full_name":"Andero Galí, Raül"},{"full_name":"Niñerola, Sergio","first_name":"Sergio","last_name":"Niñerola"},{"last_name":"Barco","first_name":"Angel","full_name":"Barco, Angel"},{"last_name":"Paoletti","first_name":"Pierre","full_name":"Paoletti, Pierre"},{"full_name":"Wesseling, John F","first_name":"John F","last_name":"Wesseling"},{"first_name":"Fabrizio","last_name":"Gardoni","full_name":"Gardoni, Fabrizio"},{"full_name":"Tavalin, Steven J","first_name":"Steven J","last_name":"Tavalin"},{"full_name":"Perez-Otaño, Isabel","last_name":"Perez-Otaño","first_name":"Isabel"}],"date_created":"2021-11-18T06:59:45Z","date_updated":"2023-08-14T11:50:50Z","volume":10},{"language":[{"iso":"eng"}],"doi":"10.1016/j.bbi.2021.07.022","quality_controlled":"1","isi":1,"main_file_link":[{"url":"https://www.zora.uzh.ch/id/eprint/208855/1/ZORA208855.pdf","open_access":"1"}],"external_id":{"pmid":["34343616"],"isi":["000702878400007"]},"oa":1,"publication_identifier":{"issn":["0889-1591"]},"month":"10","volume":97,"date_updated":"2023-10-03T09:49:18Z","date_created":"2021-08-22T22:01:21Z","author":[{"full_name":"Picard, Katherine","first_name":"Katherine","last_name":"Picard"},{"last_name":"Bisht","first_name":"Kanchan","full_name":"Bisht, Kanchan"},{"full_name":"Poggini, Silvia","first_name":"Silvia","last_name":"Poggini"},{"full_name":"Garofalo, Stefano","first_name":"Stefano","last_name":"Garofalo"},{"full_name":"Golia, Maria Teresa","last_name":"Golia","first_name":"Maria Teresa"},{"full_name":"Basilico, Bernadette","first_name":"Bernadette","last_name":"Basilico","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","orcid":"0000-0003-1843-3173"},{"full_name":"Abdallah, Fatima","last_name":"Abdallah","first_name":"Fatima"},{"full_name":"Ciano Albanese, Naomi","last_name":"Ciano Albanese","first_name":"Naomi"},{"full_name":"Amrein, Irmgard","first_name":"Irmgard","last_name":"Amrein"},{"last_name":"Vernoux","first_name":"Nathalie","full_name":"Vernoux, Nathalie"},{"first_name":"Kaushik","last_name":"Sharma","full_name":"Sharma, Kaushik"},{"full_name":"Hui, Chin Wai","first_name":"Chin Wai","last_name":"Hui"},{"full_name":"C. Savage, Julie","last_name":"C. Savage","first_name":"Julie"},{"full_name":"Limatola, Cristina","last_name":"Limatola","first_name":"Cristina"},{"last_name":"Ragozzino","first_name":"Davide","full_name":"Ragozzino, Davide"},{"last_name":"Maggi","first_name":"Laura","full_name":"Maggi, Laura"},{"full_name":"Branchi, Igor","last_name":"Branchi","first_name":"Igor"},{"last_name":"Tremblay","first_name":"Marie Ève","full_name":"Tremblay, Marie Ève"}],"publisher":"Elsevier","department":[{"_id":"GaNo"}],"publication_status":"published","pmid":1,"acknowledgement":"We acknowledge that Université Laval stands on the traditional and unceded land of the Huron-Wendat peoples; and that the University of Victoria exists on the territory of the Lekwungen peoples and that the Songhees, Esquimalt and WSÁNEÆ peoples have relationships to this land. We thank Emmanuel Planel for the access to the epifluorescence microscope and Julie-Christine Lévesque at the Bioimaging Platform of CRCHU de Québec-Université Laval for technical assistance. We also thank the Centre for Advanced Materials and Related Technology for the access to the confocal microscope with Airyscan. K.P. was supported by a doctoral scholarship from Fonds de Recherche du Québec – Santé (FRQS), an excellence award from Fondation du CHU de Québec, as well as from Centre Thématique de Recherche en Neurosciences and from Fondation Famille-Choquette. K.B. was supported by excellence scholarships from Université Laval and Fondation du CHU de Québec. S.G. is supported by FIRC-AIRC fellowship for Italy 22329/2018 and by Pilot ARISLA NKINALS 2019. C.W.H. and J.C.S. were supported by postdoctoral fellowships from FRQS. This study was funded by a Natural Sciences and Engineering Research Council of Canada (NSERC) Discovery grant (RGPIN-2014-05308) awarded to M.E.T., by ERANET neuron 2017 MicroSynDep to M.E.T. and I.B., and by the Italian Ministry of Health, grant RF-2018-12367249 to I.B, by PRIN 2017, AIRC 2019 and Ministero della Salute RF2018 to C.L. M.E.T. is a Tier II Canada Research Chair in Neurobiology of Aging and Cognition.","year":"2021","date_published":"2021-10-01T00:00:00Z","page":"423-439","article_type":"original","citation":{"mla":"Picard, Katherine, et al. “Microglial-Glucocorticoid Receptor Depletion Alters the Response of Hippocampal Microglia and Neurons in a Chronic Unpredictable Mild Stress Paradigm in Female Mice.” Brain, Behavior, and Immunity, vol. 97, Elsevier, 2021, pp. 423–39, doi:10.1016/j.bbi.2021.07.022.","short":"K. Picard, K. Bisht, S. Poggini, S. Garofalo, M.T. Golia, B. Basilico, F. Abdallah, N. Ciano Albanese, I. Amrein, N. Vernoux, K. Sharma, C.W. Hui, J. C. Savage, C. Limatola, D. Ragozzino, L. Maggi, I. Branchi, M.È. Tremblay, Brain, Behavior, and Immunity 97 (2021) 423–439.","chicago":"Picard, Katherine, Kanchan Bisht, Silvia Poggini, Stefano Garofalo, Maria Teresa Golia, Bernadette Basilico, Fatima Abdallah, et al. “Microglial-Glucocorticoid Receptor Depletion Alters the Response of Hippocampal Microglia and Neurons in a Chronic Unpredictable Mild Stress Paradigm in Female Mice.” Brain, Behavior, and Immunity. Elsevier, 2021. https://doi.org/10.1016/j.bbi.2021.07.022.","ama":"Picard K, Bisht K, Poggini S, et al. Microglial-glucocorticoid receptor depletion alters the response of hippocampal microglia and neurons in a chronic unpredictable mild stress paradigm in female mice. Brain, Behavior, and Immunity. 2021;97:423-439. doi:10.1016/j.bbi.2021.07.022","ista":"Picard K, Bisht K, Poggini S, Garofalo S, Golia MT, Basilico B, Abdallah F, Ciano Albanese N, Amrein I, Vernoux N, Sharma K, Hui CW, C. Savage J, Limatola C, Ragozzino D, Maggi L, Branchi I, Tremblay MÈ. 2021. Microglial-glucocorticoid receptor depletion alters the response of hippocampal microglia and neurons in a chronic unpredictable mild stress paradigm in female mice. Brain, Behavior, and Immunity. 97, 423–439.","apa":"Picard, K., Bisht, K., Poggini, S., Garofalo, S., Golia, M. T., Basilico, B., … Tremblay, M. È. (2021). Microglial-glucocorticoid receptor depletion alters the response of hippocampal microglia and neurons in a chronic unpredictable mild stress paradigm in female mice. Brain, Behavior, and Immunity. Elsevier. https://doi.org/10.1016/j.bbi.2021.07.022","ieee":"K. Picard et al., “Microglial-glucocorticoid receptor depletion alters the response of hippocampal microglia and neurons in a chronic unpredictable mild stress paradigm in female mice,” Brain, Behavior, and Immunity, vol. 97. Elsevier, pp. 423–439, 2021."},"publication":"Brain, Behavior, and Immunity","article_processing_charge":"No","day":"01","scopus_import":"1","oa_version":"Submitted Version","intvolume":" 97","title":"Microglial-glucocorticoid receptor depletion alters the response of hippocampal microglia and neurons in a chronic unpredictable mild stress paradigm in female mice","status":"public","_id":"9953","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","abstract":[{"text":"Chronic psychological stress is one of the most important triggers and environmental risk factors for neuropsychiatric disorders. Chronic stress can influence all organs via the secretion of stress hormones, including glucocorticoids by the adrenal glands, which coordinate the stress response across the body. In the brain, glucocorticoid receptors (GR) are expressed by various cell types including microglia, which are its resident immune cells regulating stress-induced inflammatory processes. To study the roles of microglial GR under normal homeostatic conditions and following chronic stress, we generated a mouse model in which the GR gene is depleted in microglia specifically at adulthood to prevent developmental confounds. We first confirmed that microglia were depleted in GR in our model in males and females among the cingulate cortex and the hippocampus, both stress-sensitive brain regions. Then, cohorts of microglial-GR depleted and wild-type (WT) adult female mice were housed for 3 weeks in a standard or stressful condition, using a chronic unpredictable mild stress (CUMS) paradigm. CUMS induced stress-related behavior in both microglial-GR depleted and WT animals as demonstrated by a decrease of both saccharine preference and progressive ratio breakpoint. Nevertheless, the hippocampal microglial and neural mechanisms underlying the adaptation to stress occurred differently between the two genotypes. Upon CUMS exposure, microglial morphology was altered in the WT controls, without any apparent effect in microglial-GR depleted mice. Furthermore, in the standard environment condition, GR depleted-microglia showed increased expression of pro-inflammatory genes, and genes involved in microglial homeostatic functions (such as Trem2, Cx3cr1 and Mertk). On the contrary, in CUMS condition, GR depleted-microglia showed reduced expression levels of pro-inflammatory genes and increased neuroprotective as well as anti-inflammatory genes compared to WT-microglia. Moreover, in microglial-GR depleted mice, but not in WT mice, CUMS led to a significant reduction of CA1 long-term potentiation and paired-pulse ratio. Lastly, differences in adult hippocampal neurogenesis were observed between the genotypes during normal homeostatic conditions, with microglial-GR deficiency increasing the formation of newborn neurons in the dentate gyrus subgranular zone independently from stress exposure. Together, these findings indicate that, although the deletion of microglial GR did not prevent the animal’s ability to respond to stress, it contributed to modulating hippocampal functions in both standard and stressful conditions, notably by shaping the microglial response to chronic stress.","lang":"eng"}],"type":"journal_article"},{"language":[{"iso":"eng"}],"doi":"10.1177/0271678X20965500","isi":1,"quality_controlled":"1","oa":1,"main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221757/","open_access":"1"}],"external_id":{"pmid":["33081568"],"isi":["000664214100012"]},"publication_identifier":{"eissn":["1559-7016"],"issn":["0271-678x"]},"month":"07","volume":41,"date_updated":"2023-10-18T06:45:30Z","date_created":"2020-11-06T08:39:01Z","author":[{"last_name":"Tournier","first_name":"N","full_name":"Tournier, N"},{"first_name":"S","last_name":"Goutal","full_name":"Goutal, S"},{"first_name":"S","last_name":"Mairinger","full_name":"Mairinger, S"},{"full_name":"Lozano, IH","first_name":"IH","last_name":"Lozano"},{"full_name":"Filip, T","last_name":"Filip","first_name":"T"},{"first_name":"M","last_name":"Sauberer","full_name":"Sauberer, M"},{"full_name":"Caillé, F","last_name":"Caillé","first_name":"F"},{"full_name":"Breuil, L","first_name":"L","last_name":"Breuil"},{"first_name":"J","last_name":"Stanek","full_name":"Stanek, J"},{"first_name":"AF","last_name":"Freeman","full_name":"Freeman, AF"},{"last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia"},{"last_name":"Truillet","first_name":"C","full_name":"Truillet, C"},{"full_name":"Wanek, T","last_name":"Wanek","first_name":"T"},{"full_name":"Langer, O","first_name":"O","last_name":"Langer"}],"department":[{"_id":"GaNo"}],"publisher":"SAGE Publications","publication_status":"published","pmid":1,"year":"2021","date_published":"2021-07-01T00:00:00Z","page":"1634-1646","article_type":"original","citation":{"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.","chicago":"Tournier, N, S Goutal, S Mairinger, IH Lozano, T Filip, M Sauberer, F Caillé, et al. “Complete Inhibition of ABCB1 and ABCG2 at the Blood-Brain Barrier by Co-Infusion of Erlotinib and Tariquidar to Improve Brain Delivery of the Model ABCB1/ABCG2 Substrate [11C]Erlotinib.” Journal of Cerebral Blood Flow and Metabolism. SAGE Publications, 2021. https://doi.org/10.1177/0271678X20965500.","ama":"Tournier N, Goutal S, Mairinger S, et al. Complete inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion of erlotinib and tariquidar to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib. Journal of Cerebral Blood Flow and Metabolism. 2021;41(7):1634-1646. doi:10.1177/0271678X20965500","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.","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","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."},"publication":"Journal of Cerebral Blood Flow and Metabolism","article_processing_charge":"No","day":"01","scopus_import":"1","oa_version":"Published Version","intvolume":" 41","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","_id":"8730","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","issue":"7","abstract":[{"text":"P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) restrict at the blood–brain barrier (BBB) the brain distribution of the majority of currently known molecularly targeted anticancer drugs. To improve brain delivery of dual ABCB1/ABCG2 substrates, both ABCB1 and ABCG2 need to be inhibited simultaneously at the BBB. We examined the feasibility of simultaneous ABCB1/ABCG2 inhibition with i.v. co-infusion of erlotinib and tariquidar by studying brain distribution of the model ABCB1/ABCG2 substrate [11C]erlotinib in mice and rhesus macaques with PET. Tolerability of the erlotinib/tariquidar combination was assessed in human embryonic stem cell-derived cerebral organoids. In mice and macaques, baseline brain distribution of [11C]erlotinib was low (brain distribution volume, VT,brain < 0.3 mL/cm3). Co-infusion of erlotinib and tariquidar increased VT,brain in mice by 3.0-fold and in macaques by 3.4- to 5.0-fold, while infusion of erlotinib alone or tariquidar alone led to less pronounced VT,brain increases in both species. Treatment of cerebral organoids with erlotinib/tariquidar led to an induction of Caspase-3-dependent apoptosis. Co-infusion of erlotinib/tariquidar may potentially allow for complete ABCB1/ABCG2 inhibition at the BBB, while simultaneously achieving brain-targeted EGFR inhibition. Our protocol may be applicable to enhance brain delivery of molecularly targeted anticancer drugs for a more effective treatment of brain tumors.","lang":"eng"}],"type":"journal_article"},{"department":[{"_id":"GaNo"},{"_id":"JoDa"},{"_id":"FlSc"},{"_id":"MiSi"},{"_id":"LifeSc"},{"_id":"Bio"}],"publisher":"Springer Nature","publication_status":"published","year":"2021","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).","volume":12,"date_updated":"2024-03-28T23:30:23Z","date_created":"2021-05-28T11:49:46Z","related_material":{"link":[{"url":"https://ist.ac.at/en/news/defective-gene-slows-down-brain-cells/","relation":"press_release"}],"record":[{"id":"7800","relation":"earlier_version","status":"public"},{"status":"public","relation":"dissertation_contains","id":"12401"}]},"author":[{"last_name":"Morandell","first_name":"Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","full_name":"Morandell, Jasmin"},{"full_name":"Schwarz, Lena A","id":"29A8453C-F248-11E8-B48F-1D18A9856A87","last_name":"Schwarz","first_name":"Lena A"},{"full_name":"Basilico, Bernadette","orcid":"0000-0003-1843-3173","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","last_name":"Basilico","first_name":"Bernadette"},{"full_name":"Tasciyan, Saren","orcid":"0000-0003-1671-393X","id":"4323B49C-F248-11E8-B48F-1D18A9856A87","last_name":"Tasciyan","first_name":"Saren"},{"full_name":"Dimchev, Georgi A","id":"38C393BE-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0001-8370-6161","first_name":"Georgi A","last_name":"Dimchev"},{"last_name":"Nicolas","first_name":"Armel","id":"2A103192-F248-11E8-B48F-1D18A9856A87","full_name":"Nicolas, Armel"},{"full_name":"Sommer, Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","first_name":"Christoph M","last_name":"Sommer"},{"full_name":"Kreuzinger, Caroline","id":"382077BA-F248-11E8-B48F-1D18A9856A87","first_name":"Caroline","last_name":"Kreuzinger"},{"orcid":"0000-0002-9033-9096","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","last_name":"Dotter","first_name":"Christoph","full_name":"Dotter, Christoph"},{"last_name":"Knaus","first_name":"Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","full_name":"Knaus, Lisa"},{"full_name":"Dobler, Zoe","id":"D23090A2-9057-11EA-883A-A8396FC7A38F","last_name":"Dobler","first_name":"Zoe"},{"full_name":"Cacci, Emanuele","last_name":"Cacci","first_name":"Emanuele"},{"full_name":"Schur, Florian KM","last_name":"Schur","first_name":"Florian KM","orcid":"0000-0003-4790-8078","id":"48AD8942-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","last_name":"Danzl","first_name":"Johann G"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino","full_name":"Novarino, Gaia"}],"article_number":"3058","ec_funded":1,"file_date_updated":"2021-05-28T12:39:43Z","project":[{"_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411","call_identifier":"H2020","name":"ISTplus - Postdoctoral Fellowships"},{"call_identifier":"H2020","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","grant_number":"715508","_id":"25444568-B435-11E9-9278-68D0E5697425"},{"grant_number":"W1232-B24","_id":"2548AE96-B435-11E9-9278-68D0E5697425","call_identifier":"FWF","name":"Molecular Drug Targets"},{"name":"Neural stem cells in autism and epilepsy","_id":"05A0D778-7A3F-11EA-A408-12923DDC885E","grant_number":"F07807"},{"call_identifier":"FWF","name":"Optical control of synaptic function via adhesion molecules","grant_number":"I03600","_id":"265CB4D0-B435-11E9-9278-68D0E5697425"}],"isi":1,"quality_controlled":"1","external_id":{"isi":["000658769900010"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"PreCl"}],"doi":"10.1038/s41467-021-23123-x","publication_identifier":{"eissn":["2041-1723"]},"month":"05","intvolume":" 12","title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","status":"public","ddc":["572"],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"9429","file":[{"access_level":"open_access","file_name":"2021_NatureCommunications_Morandell.pdf","file_size":9358599,"content_type":"application/pdf","creator":"kschuh","relation":"main_file","file_id":"9430","checksum":"337e0f7959c35ec959984cacdcb472ba","success":1,"date_updated":"2021-05-28T12:39:43Z","date_created":"2021-05-28T12:39:43Z"}],"oa_version":"Published Version","type":"journal_article","issue":"1","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."}],"article_type":"original","citation":{"mla":"Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” Nature Communications, vol. 12, no. 1, 3058, Springer Nature, 2021, doi:10.1038/s41467-021-23123-x.","short":"J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, G.A. Dimchev, A. Nicolas, C.M. Sommer, C. Kreuzinger, C. Dotter, L. Knaus, Z. Dobler, E. Cacci, F.K. Schur, J.G. Danzl, G. Novarino, Nature Communications 12 (2021).","chicago":"Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan, Georgi A Dimchev, Armel Nicolas, Christoph M Sommer, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” Nature Communications. Springer Nature, 2021. https://doi.org/10.1038/s41467-021-23123-x.","ama":"Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. 2021;12(1). doi:10.1038/s41467-021-23123-x","ista":"Morandell J, Schwarz LA, Basilico B, Tasciyan S, Dimchev GA, Nicolas A, Sommer CM, Kreuzinger C, Dotter C, Knaus L, Dobler Z, Cacci E, Schur FK, Danzl JG, Novarino G. 2021. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. 12(1), 3058.","ieee":"J. Morandell et al., “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” Nature Communications, vol. 12, no. 1. Springer Nature, 2021.","apa":"Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Dimchev, G. A., Nicolas, A., … Novarino, G. (2021). Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-021-23123-x"},"publication":"Nature Communications","date_published":"2021-05-24T00:00:00Z","keyword":["General Biochemistry","Genetics and Molecular Biology"],"article_processing_charge":"No","has_accepted_license":"1","day":"24"},{"scopus_import":"1","day":"01","article_processing_charge":"No","article_type":"review","page":"3-11","publication":"Clinical Genetics","citation":{"mla":"Avagliano, Laura, et al. “Chromatinopathies: A Focus on Cornelia de Lange Syndrome.” Clinical Genetics, vol. 97, no. 1, Wiley, 2020, pp. 3–11, doi:10.1111/cge.13674.","short":"L. Avagliano, I. Parenti, P. Grazioli, E. Di Fede, C. Parodi, M. Mariani, F.J. Kaiser, A. Selicorni, C. Gervasini, V. Massa, Clinical Genetics 97 (2020) 3–11.","chicago":"Avagliano, Laura, Ilaria Parenti, Paolo Grazioli, Elisabetta Di Fede, Chiara Parodi, Milena Mariani, Frank J. Kaiser, Angelo Selicorni, Cristina Gervasini, and Valentina Massa. “Chromatinopathies: A Focus on Cornelia de Lange Syndrome.” Clinical Genetics. Wiley, 2020. https://doi.org/10.1111/cge.13674.","ama":"Avagliano L, Parenti I, Grazioli P, et al. Chromatinopathies: A focus on Cornelia de Lange syndrome. Clinical Genetics. 2020;97(1):3-11. doi:10.1111/cge.13674","ista":"Avagliano L, Parenti I, Grazioli P, Di Fede E, Parodi C, Mariani M, Kaiser FJ, Selicorni A, Gervasini C, Massa V. 2020. Chromatinopathies: A focus on Cornelia de Lange syndrome. Clinical Genetics. 97(1), 3–11.","apa":"Avagliano, L., Parenti, I., Grazioli, P., Di Fede, E., Parodi, C., Mariani, M., … Massa, V. (2020). Chromatinopathies: A focus on Cornelia de Lange syndrome. Clinical Genetics. Wiley. https://doi.org/10.1111/cge.13674","ieee":"L. Avagliano et al., “Chromatinopathies: A focus on Cornelia de Lange syndrome,” Clinical Genetics, vol. 97, no. 1. Wiley, pp. 3–11, 2020."},"date_published":"2020-01-01T00:00:00Z","type":"journal_article","abstract":[{"text":"In recent years, many genes have been associated with chromatinopathies classified as “Cornelia de Lange Syndrome‐like.” It is known that the phenotype of these patients becomes less recognizable, overlapping to features characteristic of other syndromes caused by genetic variants affecting different regulators of chromatin structure and function. Therefore, Cornelia de Lange syndrome diagnosis might be arduous due to the seldom discordance between unexpected molecular diagnosis and clinical evaluation. Here, we review the molecular features of Cornelia de Lange syndrome, supporting the hypothesis that “CdLS‐like syndromes” are part of a larger “rare disease family” sharing multiple clinical features and common disrupted molecular pathways.","lang":"eng"}],"issue":"1","title":"Chromatinopathies: A focus on Cornelia de Lange syndrome","status":"public","intvolume":" 97","_id":"7149","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","oa_version":"None","month":"01","publication_identifier":{"issn":["0009-9163"],"eissn":["1399-0004"]},"isi":1,"quality_controlled":"1","external_id":{"pmid":["31721174"],"isi":["000562561800001"]},"language":[{"iso":"eng"}],"doi":"10.1111/cge.13674","publication_status":"published","publisher":"Wiley","department":[{"_id":"GaNo"}],"year":"2020","acknowledgement":" Dipartimento DiSS, Università degli Studi di Milano, Grant/Award Number: Linea 2; Fondazione Cariplo, Grant/Award Number: 2015-0783; German Federal Ministry of Education and Research (BMBF), Grant/Award Number: CHROMATIN-Net; Medical Faculty of the University of Lübeck, Grant/Award Number: J09-2017; Nickel & Co S.p.A.; Università degli Studi di Milano, Grant/Award Numbers: Molecular & Translational Medicine PhD Scholarship, Translational Medicine PhD Scholarship","pmid":1,"date_created":"2019-12-04T16:10:59Z","date_updated":"2023-08-17T14:06:20Z","volume":97,"author":[{"full_name":"Avagliano, Laura","first_name":"Laura","last_name":"Avagliano"},{"full_name":"Parenti, Ilaria","id":"D93538B0-5B71-11E9-AC62-02EBE5697425","first_name":"Ilaria","last_name":"Parenti"},{"full_name":"Grazioli, Paolo","last_name":"Grazioli","first_name":"Paolo"},{"full_name":"Di Fede, Elisabetta","last_name":"Di Fede","first_name":"Elisabetta"},{"full_name":"Parodi, Chiara","last_name":"Parodi","first_name":"Chiara"},{"last_name":"Mariani","first_name":"Milena","full_name":"Mariani, Milena"},{"last_name":"Kaiser","first_name":"Frank J.","full_name":"Kaiser, Frank J."},{"last_name":"Selicorni","first_name":"Angelo","full_name":"Selicorni, Angelo"},{"full_name":"Gervasini, Cristina","first_name":"Cristina","last_name":"Gervasini"},{"first_name":"Valentina","last_name":"Massa","full_name":"Massa, Valentina"}]},{"publication_identifier":{"eissn":["14220067"],"issn":["16616596"]},"month":"02","language":[{"iso":"eng"}],"doi":"10.3390/ijms21031042","quality_controlled":"1","isi":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000522551606028"]},"oa":1,"file_date_updated":"2020-07-14T12:47:59Z","article_number":"1042","volume":21,"date_updated":"2023-08-18T06:35:41Z","date_created":"2020-02-16T23:00:49Z","author":[{"last_name":"Latorre-Pellicer","first_name":"Ana","full_name":"Latorre-Pellicer, Ana"},{"first_name":"Ángela","last_name":"Ascaso","full_name":"Ascaso, Ángela"},{"last_name":"Trujillano","first_name":"Laura","full_name":"Trujillano, Laura"},{"last_name":"Gil-Salvador","first_name":"Marta","full_name":"Gil-Salvador, Marta"},{"full_name":"Arnedo, Maria","first_name":"Maria","last_name":"Arnedo"},{"first_name":"Cristina","last_name":"Lucia-Campos","full_name":"Lucia-Campos, Cristina"},{"first_name":"Rebeca","last_name":"Antoñanzas-Pérez","full_name":"Antoñanzas-Pérez, Rebeca"},{"last_name":"Marcos-Alcalde","first_name":"Iñigo","full_name":"Marcos-Alcalde, Iñigo"},{"full_name":"Parenti, Ilaria","first_name":"Ilaria","last_name":"Parenti","id":"D93538B0-5B71-11E9-AC62-02EBE5697425"},{"full_name":"Bueno-Lozano, Gloria","first_name":"Gloria","last_name":"Bueno-Lozano"},{"full_name":"Musio, Antonio","first_name":"Antonio","last_name":"Musio"},{"full_name":"Puisac, Beatriz","last_name":"Puisac","first_name":"Beatriz"},{"first_name":"Frank J.","last_name":"Kaiser","full_name":"Kaiser, Frank J."},{"full_name":"Ramos, Feliciano J.","first_name":"Feliciano J.","last_name":"Ramos"},{"last_name":"Gómez-Puertas","first_name":"Paulino","full_name":"Gómez-Puertas, Paulino"},{"first_name":"Juan","last_name":"Pié","full_name":"Pié, Juan"}],"publisher":"MDPI","department":[{"_id":"GaNo"}],"publication_status":"published","year":"2020","has_accepted_license":"1","article_processing_charge":"No","day":"04","scopus_import":"1","date_published":"2020-02-04T00:00:00Z","article_type":"original","citation":{"mla":"Latorre-Pellicer, Ana, et al. “Evaluating Face2Gene as a Tool to Identify Cornelia de Lange Syndrome by Facial Phenotypes.” International Journal of Molecular Sciences, vol. 21, no. 3, 1042, MDPI, 2020, doi:10.3390/ijms21031042.","short":"A. Latorre-Pellicer, Á. Ascaso, L. Trujillano, M. Gil-Salvador, M. Arnedo, C. Lucia-Campos, R. Antoñanzas-Pérez, I. Marcos-Alcalde, I. Parenti, G. Bueno-Lozano, A. Musio, B. Puisac, F.J. Kaiser, F.J. Ramos, P. Gómez-Puertas, J. Pié, International Journal of Molecular Sciences 21 (2020).","chicago":"Latorre-Pellicer, Ana, Ángela Ascaso, Laura Trujillano, Marta Gil-Salvador, Maria Arnedo, Cristina Lucia-Campos, Rebeca Antoñanzas-Pérez, et al. “Evaluating Face2Gene as a Tool to Identify Cornelia de Lange Syndrome by Facial Phenotypes.” International Journal of Molecular Sciences. MDPI, 2020. https://doi.org/10.3390/ijms21031042.","ama":"Latorre-Pellicer A, Ascaso Á, Trujillano L, et al. Evaluating Face2Gene as a tool to identify Cornelia de Lange syndrome by facial phenotypes. International Journal of Molecular Sciences. 2020;21(3). doi:10.3390/ijms21031042","ista":"Latorre-Pellicer A, Ascaso Á, Trujillano L, Gil-Salvador M, Arnedo M, Lucia-Campos C, Antoñanzas-Pérez R, Marcos-Alcalde I, Parenti I, Bueno-Lozano G, Musio A, Puisac B, Kaiser FJ, Ramos FJ, Gómez-Puertas P, Pié J. 2020. Evaluating Face2Gene as a tool to identify Cornelia de Lange syndrome by facial phenotypes. International Journal of Molecular Sciences. 21(3), 1042.","apa":"Latorre-Pellicer, A., Ascaso, Á., Trujillano, L., Gil-Salvador, M., Arnedo, M., Lucia-Campos, C., … Pié, J. (2020). Evaluating Face2Gene as a tool to identify Cornelia de Lange syndrome by facial phenotypes. International Journal of Molecular Sciences. MDPI. https://doi.org/10.3390/ijms21031042","ieee":"A. Latorre-Pellicer et al., “Evaluating Face2Gene as a tool to identify Cornelia de Lange syndrome by facial phenotypes,” International Journal of Molecular Sciences, vol. 21, no. 3. MDPI, 2020."},"publication":"International Journal of Molecular Sciences","issue":"3","abstract":[{"text":"Characteristic or classic phenotype of Cornelia de Lange syndrome (CdLS) is associated with a recognisable facial pattern. However, the heterogeneity in causal genes and the presence of overlapping syndromes have made it increasingly difficult to diagnose only by clinical features. DeepGestalt technology, and its app Face2Gene, is having a growing impact on the diagnosis and management of genetic diseases by analysing the features of affected individuals. Here, we performed a phenotypic study on a cohort of 49 individuals harbouring causative variants in known CdLS genes in order to evaluate Face2Gene utility and sensitivity in the clinical diagnosis of CdLS. Based on the profile images of patients, a diagnosis of CdLS was within the top five predicted syndromes for 97.9% of our cases and even listed as first prediction for 83.7%. The age of patients did not seem to affect the prediction accuracy, whereas our results indicate a correlation between the clinical score and affected genes. Furthermore, each gene presents a different pattern recognition that may be used to develop new neural networks with the goal of separating different genetic subtypes in CdLS. Overall, we conclude that computer-assisted image analysis based on deep learning could support the clinical diagnosis of CdLS.","lang":"eng"}],"type":"journal_article","file":[{"file_size":4271234,"content_type":"application/pdf","creator":"dernst","access_level":"open_access","file_name":"2020_IntMolecSciences_Latorre.pdf","checksum":"0e6658c4fe329d55d4d9bef01c5b15d0","date_updated":"2020-07-14T12:47:59Z","date_created":"2020-02-18T07:49:22Z","relation":"main_file","file_id":"7496"}],"oa_version":"Published Version","intvolume":" 21","status":"public","title":"Evaluating Face2Gene as a tool to identify Cornelia de Lange syndrome by facial phenotypes","ddc":["570"],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"7488"},{"isi":1,"quality_controlled":"1","external_id":{"pmid":["32118314"],"isi":["000517335000001"]},"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"oa":1,"language":[{"iso":"eng"}],"doi":"10.15252/embj.2019103358","month":"03","publication_identifier":{"issn":["02614189"],"eissn":["14602075"]},"publication_status":"published","publisher":"EMBO Press","department":[{"_id":"GaNo"}],"acknowledgement":"We thank T. Stauber and T. Breiderhoff for cloning expression constructs; K. Räbel, S. Hohensee, and C. Backhaus for technical assistance; R. Jahn (MPIbpc, Göttingen) for providing the equipment required for SV purification; and A\r\nWoehler (MDC, Berlin) for assistance with SV imaging. Supported, in part, by grants from the Deutsche Forschungsgemeinschaft (JE164/9-2, SFB740 TP C5, FOR 2625 (JE164/14-1), NeuroCure Cluster of Excellence), the European Research Council Advanced Grant CYTOVOLION (ERC 294435) and the Prix Louis-Jeantet de Médecine to TJJ, and Peter and Traudl Engelhorn fellowship to ZF.","year":"2020","pmid":1,"date_created":"2020-03-15T23:00:55Z","date_updated":"2023-08-18T07:07:36Z","volume":39,"author":[{"full_name":"Weinert, Stefanie","first_name":"Stefanie","last_name":"Weinert"},{"full_name":"Gimber, Niclas","last_name":"Gimber","first_name":"Niclas"},{"full_name":"Deuschel, Dorothea","last_name":"Deuschel","first_name":"Dorothea"},{"last_name":"Stuhlmann","first_name":"Till","full_name":"Stuhlmann, Till"},{"full_name":"Puchkov, Dmytro","first_name":"Dmytro","last_name":"Puchkov"},{"full_name":"Farsi, Zohreh","last_name":"Farsi","first_name":"Zohreh"},{"full_name":"Ludwig, Carmen F.","first_name":"Carmen F.","last_name":"Ludwig"},{"full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia"},{"first_name":"Karen I.","last_name":"López-Cayuqueo","full_name":"López-Cayuqueo, Karen I."},{"full_name":"Planells-Cases, Rosa","last_name":"Planells-Cases","first_name":"Rosa"},{"first_name":"Thomas J.","last_name":"Jentsch","full_name":"Jentsch, Thomas J."}],"article_number":"e103358","license":"https://creativecommons.org/licenses/by-nc-nd/4.0/","file_date_updated":"2020-07-14T12:48:00Z","article_type":"original","publication":"EMBO Journal","citation":{"mla":"Weinert, Stefanie, et al. “Uncoupling Endosomal CLC Chloride/Proton Exchange Causes Severe Neurodegeneration.” EMBO Journal, vol. 39, e103358, EMBO Press, 2020, doi:10.15252/embj.2019103358.","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).","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.","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","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.","ieee":"S. Weinert et al., “Uncoupling endosomal CLC chloride/proton exchange causes severe neurodegeneration,” EMBO Journal, vol. 39. EMBO Press, 2020.","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"},"date_published":"2020-03-02T00:00:00Z","scopus_import":"1","day":"02","article_processing_charge":"No","has_accepted_license":"1","ddc":["570"],"title":"Uncoupling endosomal CLC chloride/proton exchange causes severe neurodegeneration","status":"public","intvolume":" 39","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"7586","oa_version":"Published Version","file":[{"content_type":"application/pdf","file_size":12243278,"creator":"dernst","file_name":"2020_EMBO_Weinert.pdf","access_level":"open_access","date_created":"2020-03-23T13:51:11Z","date_updated":"2020-07-14T12:48:00Z","checksum":"82750a7a93e3740decbce8474004111a","relation":"main_file","file_id":"7615"}],"type":"journal_article","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."}]},{"type":"journal_article","abstract":[{"text":"The NIPBL/MAU2 heterodimer loads cohesin onto chromatin. Mutations inNIPBLaccount for most cases ofthe rare developmental disorder Cornelia de Lange syndrome (CdLS). Here we report aMAU2 variant causing CdLS, a deletion of seven amino acids that impairs the interaction between MAU2 and the NIPBL N terminus.Investigating this interaction, we discovered that MAU2 and the NIPBL N terminus are largely dispensable fornormal cohesin and NIPBL function in cells with a NIPBL early truncating mutation. Despite a predicted fataloutcome of an out-of-frame single nucleotide duplication inNIPBL, engineered in two different cell lines,alternative translation initiation yields a form of NIPBL missing N-terminal residues. This form cannot interactwith MAU2, but binds DNA and mediates cohesin loading. Altogether, our work reveals that cohesin loading can occur independently of functional NIPBL/MAU2 complexes and highlights a novel mechanism protectiveagainst out-of-frame mutations that is potentially relevant for other genetic conditions.","lang":"eng"}],"issue":"7","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"7877","status":"public","ddc":["570"],"title":"MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader subunits and cause Cornelia de Lange syndrome","intvolume":" 31","oa_version":"Published Version","file":[{"file_id":"7892","relation":"main_file","date_created":"2020-05-26T11:05:01Z","date_updated":"2020-07-14T12:48:04Z","checksum":"64d8f7467731ee5c166b10b939b8310b","file_name":"2020_CellReports_Parenti.pdf","access_level":"open_access","creator":"dernst","content_type":"application/pdf","file_size":4695682}],"scopus_import":"1","day":"19","has_accepted_license":"1","article_processing_charge":"No","publication":"Cell Reports","citation":{"chicago":"Parenti, Ilaria, Farah Diab, Sara Ruiz Gil, Eskeatnaf Mulugeta, Valentina Casa, Riccardo Berutti, Rutger W.W. Brouwer, et al. “MAU2 and NIPBL Variants Impair the Heterodimerization of the Cohesin Loader Subunits and Cause Cornelia de Lange Syndrome.” Cell Reports. Elsevier, 2020. https://doi.org/10.1016/j.celrep.2020.107647.","short":"I. Parenti, F. Diab, S.R. Gil, E. Mulugeta, V. Casa, R. Berutti, R.W.W. Brouwer, V. Dupé, J. Eckhold, E. Graf, B. Puisac, F. Ramos, T. Schwarzmayr, M.M. Gines, T. Van Staveren, W.F.J. Van Ijcken, T.M. Strom, J. Pié, E. Watrin, F.J. Kaiser, K.S. Wendt, Cell Reports 31 (2020).","mla":"Parenti, Ilaria, et al. “MAU2 and NIPBL Variants Impair the Heterodimerization of the Cohesin Loader Subunits and Cause Cornelia de Lange Syndrome.” Cell Reports, vol. 31, no. 7, 107647, Elsevier, 2020, doi:10.1016/j.celrep.2020.107647.","ieee":"I. Parenti et al., “MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader subunits and cause Cornelia de Lange syndrome,” Cell Reports, vol. 31, no. 7. Elsevier, 2020.","apa":"Parenti, I., Diab, F., Gil, S. R., Mulugeta, E., Casa, V., Berutti, R., … Wendt, K. S. (2020). MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader subunits and cause Cornelia de Lange syndrome. Cell Reports. Elsevier. https://doi.org/10.1016/j.celrep.2020.107647","ista":"Parenti I, Diab F, Gil SR, Mulugeta E, Casa V, Berutti R, Brouwer RWW, Dupé V, Eckhold J, Graf E, Puisac B, Ramos F, Schwarzmayr T, Gines MM, Van Staveren T, Van Ijcken WFJ, Strom TM, Pié J, Watrin E, Kaiser FJ, Wendt KS. 2020. MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader subunits and cause Cornelia de Lange syndrome. Cell Reports. 31(7), 107647.","ama":"Parenti I, Diab F, Gil SR, et al. MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader subunits and cause Cornelia de Lange syndrome. Cell Reports. 2020;31(7). doi:10.1016/j.celrep.2020.107647"},"article_type":"original","date_published":"2020-05-19T00:00:00Z","article_number":"107647","file_date_updated":"2020-07-14T12:48:04Z","year":"2020","publication_status":"published","publisher":"Elsevier","department":[{"_id":"GaNo"}],"author":[{"first_name":"Ilaria","last_name":"Parenti","id":"D93538B0-5B71-11E9-AC62-02EBE5697425","full_name":"Parenti, Ilaria"},{"full_name":"Diab, Farah","first_name":"Farah","last_name":"Diab"},{"first_name":"Sara Ruiz","last_name":"Gil","full_name":"Gil, Sara Ruiz"},{"full_name":"Mulugeta, Eskeatnaf","last_name":"Mulugeta","first_name":"Eskeatnaf"},{"full_name":"Casa, Valentina","last_name":"Casa","first_name":"Valentina"},{"last_name":"Berutti","first_name":"Riccardo","full_name":"Berutti, Riccardo"},{"first_name":"Rutger W.W.","last_name":"Brouwer","full_name":"Brouwer, Rutger W.W."},{"last_name":"Dupé","first_name":"Valerie","full_name":"Dupé, Valerie"},{"full_name":"Eckhold, Juliane","last_name":"Eckhold","first_name":"Juliane"},{"full_name":"Graf, Elisabeth","first_name":"Elisabeth","last_name":"Graf"},{"last_name":"Puisac","first_name":"Beatriz","full_name":"Puisac, Beatriz"},{"full_name":"Ramos, Feliciano","first_name":"Feliciano","last_name":"Ramos"},{"last_name":"Schwarzmayr","first_name":"Thomas","full_name":"Schwarzmayr, Thomas"},{"full_name":"Gines, Macarena Moronta","first_name":"Macarena Moronta","last_name":"Gines"},{"full_name":"Van Staveren, Thomas","first_name":"Thomas","last_name":"Van Staveren"},{"full_name":"Van Ijcken, Wilfred F.J.","first_name":"Wilfred F.J.","last_name":"Van Ijcken"},{"full_name":"Strom, Tim M.","first_name":"Tim M.","last_name":"Strom"},{"first_name":"Juan","last_name":"Pié","full_name":"Pié, Juan"},{"last_name":"Watrin","first_name":"Erwan","full_name":"Watrin, Erwan"},{"first_name":"Frank J.","last_name":"Kaiser","full_name":"Kaiser, Frank J."},{"last_name":"Wendt","first_name":"Kerstin S.","full_name":"Wendt, Kerstin S."}],"date_created":"2020-05-24T22:00:57Z","date_updated":"2023-08-21T06:27:47Z","volume":31,"month":"05","publication_identifier":{"eissn":["22111247"]},"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"oa":1,"external_id":{"isi":["000535655200005"]},"isi":1,"quality_controlled":"1","doi":"10.1016/j.celrep.2020.107647","language":[{"iso":"eng"}]},{"day":"01","has_accepted_license":"1","article_processing_charge":"No","scopus_import":"1","date_published":"2020-08-01T00:00:00Z","article_type":"original","page":"608-621","publication":"Trends in Neurosciences","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","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.","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","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.","short":"I. Parenti, L.E. Garcia Rabaneda, H. Schön, G. Novarino, Trends in Neurosciences 43 (2020) 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.","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."},"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."}],"issue":"8","type":"journal_article","file":[{"creator":"dernst","file_size":1439550,"content_type":"application/pdf","file_name":"2020_TrendsNeuroscience_Parenti.pdf","access_level":"open_access","date_updated":"2020-11-25T09:43:40Z","date_created":"2020-11-25T09:43:40Z","success":1,"checksum":"67db0251b1d415ae59005f876fcf9e34","file_id":"8805","relation":"main_file"}],"oa_version":"Published Version","title":"Neurodevelopmental disorders: From genetics to functional pathways","ddc":["570"],"status":"public","intvolume":" 43","_id":"7957","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","month":"08","publication_identifier":{"eissn":["1878108X"],"issn":["01662236"]},"language":[{"iso":"eng"}],"doi":"10.1016/j.tins.2020.05.004","isi":1,"quality_controlled":"1","project":[{"name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425","grant_number":"715508"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"isi":["000553090600008"],"pmid":["32507511"]},"oa":1,"file_date_updated":"2020-11-25T09:43:40Z","ec_funded":1,"date_created":"2020-06-14T22:00:49Z","date_updated":"2023-08-21T08:25:31Z","volume":43,"author":[{"first_name":"Ilaria","last_name":"Parenti","id":"D93538B0-5B71-11E9-AC62-02EBE5697425","full_name":"Parenti, Ilaria"},{"last_name":"Garcia Rabaneda","first_name":"Luis E","id":"33D1B084-F248-11E8-B48F-1D18A9856A87","full_name":"Garcia Rabaneda, Luis E"},{"full_name":"Schön, Hanna","id":"C8E17EDC-D7AA-11E9-B7B7-45ECE5697425","last_name":"Schön","first_name":"Hanna"},{"full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia"}],"publication_status":"published","publisher":"Elsevier","department":[{"_id":"GaNo"}],"acknowledgement":"We wish to thank Jasmin Morandell for generously sharing Figure 2. This work was supported by the European Research Council Starting Grant (grant 715508 ) to G.N.","year":"2020","pmid":1},{"file":[{"content_type":"application/pdf","file_size":16155786,"creator":"jmorande","file_name":"Jasmin_Morandell_Thesis-2020_final.pdf","access_level":"open_access","date_created":"2020-10-07T14:41:49Z","date_updated":"2021-10-16T22:30:04Z","checksum":"7ee83e42de3e5ce2fedb44dff472f75f","relation":"main_file","file_id":"8621","embargo":"2021-10-15"},{"file_id":"8622","relation":"source_file","checksum":"5e0464af453734210ce7aab7b4a92e3a","date_updated":"2021-10-16T22:30:04Z","date_created":"2020-10-07T14:45:07Z","access_level":"closed","file_name":"Jasmin_Morandell_Thesis-2020_final.zip","embargo_to":"open_access","creator":"jmorande","content_type":"application/x-zip-compressed","file_size":24344152}],"oa_version":"Published Version","ddc":["610"],"status":"public","title":"Illuminating the role of Cul3 in autism spectrum disorder pathogenesis","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"8620","abstract":[{"lang":"eng","text":"The development of the human brain occurs through a tightly regulated series of dynamic and adaptive processes during prenatal and postnatal life. A disruption of this strictly orchestrated series of events can lead to a number of neurodevelopmental conditions, including Autism Spectrum Disorders (ASDs). ASDs are a very common, etiologically and phenotypically heterogeneous group of disorders sharing the core symptoms of social interaction and communication deficits and restrictive and repetitive interests and behaviors. They are estimated to affect one in 59 individuals in the U.S. and, over the last three decades, mutations in more than a hundred genetic loci have been convincingly linked to ASD pathogenesis. Yet, for the vast majority of these ASD-risk genes their role during brain development and precise molecular function still remain elusive.\r\nDe novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin 3 (CUL3) lead to ASD. In the study described here, we used Cul3 mouse models to evaluate the consequences of Cul3 mutations in vivo. Our results show that Cul3 heterozygous knockout mice exhibit deficits in motor coordination as well as ASD-relevant social and cognitive impairments. Cul3+/-, Cul3+/fl Emx1-Cre and Cul3fl/fl Emx1-Cre mutant brains display cortical lamination abnormalities due to defective migration of post-mitotic excitatory neurons, as well as reduced numbers of excitatory and inhibitory neurons. In line with the observed abnormal cortical organization, Cul3 heterozygous deletion is associated with decreased spontaneous excitatory and inhibitory activity in the cortex. At the molecular level we show that Cul3 regulates cytoskeletal and adhesion protein abundance in the mouse embryonic cortex. Abnormal regulation of cytoskeletal proteins in Cul3 mutant neural cells results in atypical organization of the actin mesh at the cell leading edge. Of note, heterozygous deletion of Cul3 in adult mice does not induce the majority of the behavioral defects observed in constitutive Cul3 haploinsufficient animals, pointing to a critical time-window for Cul3 deficiency.\r\nIn conclusion, our data indicate that Cul3 plays a critical role in the regulation of cytoskeletal proteins and neuronal migration. ASD-associated defects and behavioral abnormalities are primarily due to dosage sensitive Cul3 functions at early brain developmental stages."}],"alternative_title":["ISTA Thesis"],"type":"dissertation","date_published":"2020-10-12T00:00:00Z","page":"138","citation":{"chicago":"Morandell, Jasmin. “Illuminating the Role of Cul3 in Autism Spectrum Disorder Pathogenesis.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8620.","mla":"Morandell, Jasmin. Illuminating the Role of Cul3 in Autism Spectrum Disorder Pathogenesis. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8620.","short":"J. Morandell, Illuminating the Role of Cul3 in Autism Spectrum Disorder Pathogenesis, Institute of Science and Technology Austria, 2020.","ista":"Morandell J. 2020. Illuminating the role of Cul3 in autism spectrum disorder pathogenesis. Institute of Science and Technology Austria.","apa":"Morandell, J. (2020). Illuminating the role of Cul3 in autism spectrum disorder pathogenesis. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8620","ieee":"J. Morandell, “Illuminating the role of Cul3 in autism spectrum disorder pathogenesis,” Institute of Science and Technology Austria, 2020.","ama":"Morandell J. Illuminating the role of Cul3 in autism spectrum disorder pathogenesis. 2020. doi:10.15479/AT:ISTA:8620"},"has_accepted_license":"1","article_processing_charge":"No","day":"12","date_created":"2020-10-07T14:53:13Z","date_updated":"2023-09-07T13:22:14Z","related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"7800"},{"id":"8131","status":"public","relation":"part_of_dissertation"}]},"author":[{"id":"4739D480-F248-11E8-B48F-1D18A9856A87","first_name":"Jasmin","last_name":"Morandell","full_name":"Morandell, Jasmin"}],"department":[{"_id":"GaNo"}],"publisher":"Institute of Science and Technology Austria","publication_status":"published","acknowledgement":"I would like to especially thank Armel Nicolas from the Proteomics and Christoph Sommer from the Bioimaging Facilities for the data analysis, and to thank the team of the Preclinical Facility, especially Sabina Deixler, Angela Schlerka, Anita Lepold, Mihalea Mihai and Michael Schun for taking care of the mouse line maintenance and their great support.","year":"2020","file_date_updated":"2021-10-16T22:30:04Z","language":[{"iso":"eng"}],"supervisor":[{"first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"}],"acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"degree_awarded":"PhD","doi":"10.15479/AT:ISTA:8620","project":[{"_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24","name":"Molecular Drug Targets","call_identifier":"FWF"},{"_id":"05A0D778-7A3F-11EA-A408-12923DDC885E","grant_number":"F07807","name":"Neural stem cells in autism and epilepsy"}],"oa":1,"publication_identifier":{"issn":["2663-337X"]},"month":"10"},{"article_processing_charge":"No","has_accepted_license":"1","day":"11","date_published":"2020-01-11T00:00:00Z","citation":{"short":"J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, A. Nicolas, C.M. Sommer, C. Kreuzinger, L. Knaus, Z. Dobler, E. Cacci, J.G. Danzl, G. Novarino, BioRxiv (n.d.).","mla":"Morandell, Jasmin, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” BioRxiv, Cold Spring Harbor Laboratory, doi:10.1101/2020.01.10.902064 .","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 .","ama":"Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. bioRxiv. doi:10.1101/2020.01.10.902064 ","ieee":"J. Morandell et al., “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” bioRxiv. Cold Spring Harbor Laboratory.","apa":"Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Nicolas, A., Sommer, C. M., … Novarino, G. (n.d.). Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.01.10.902064 ","ista":"Morandell J, Schwarz LA, Basilico B, Tasciyan S, Nicolas A, Sommer CM, Kreuzinger C, Knaus L, Dobler Z, Cacci E, Danzl JG, Novarino G. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. bioRxiv, 10.1101/2020.01.10.902064 ."},"publication":"bioRxiv","abstract":[{"text":"De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 (CUL3) lead to autism spectrum disorder (ASD). Here, we used Cul3 mouse models to evaluate the consequences of Cul3 mutations in vivo. Our results show that Cul3 haploinsufficient mice exhibit deficits in motor coordination as well as ASD-relevant social and cognitive impairments. Cul3 mutant brain displays cortical lamination abnormalities due to defective neuronal migration and reduced numbers of excitatory and inhibitory neurons. In line with the observed abnormal columnar organization, Cul3 haploinsufficiency is associated with decreased spontaneous excitatory and inhibitory activity in the cortex. At the molecular level, employing a quantitative proteomic approach, we show that Cul3 regulates cytoskeletal and adhesion protein abundance in mouse embryos. Abnormal regulation of cytoskeletal proteins in Cul3 mutant neuronal cells results in atypical organization of the actin mesh at the cell leading edge, likely causing the observed migration deficits. In contrast to these important functions early in development, Cul3 deficiency appears less relevant at adult stages. In fact, induction of Cul3 haploinsufficiency in adult mice does not result in the behavioral defects observed in constitutive Cul3 haploinsufficient animals. Taken together, our data indicate that Cul3 has a critical role in the regulation of cytoskeletal proteins and neuronal migration and that ASD-associated defects and behavioral abnormalities are primarily due to Cul3 functions at early developmental stages.","lang":"eng"}],"type":"preprint","oa_version":"Preprint","file":[{"file_size":2931370,"content_type":"application/pdf","creator":"rsix","file_name":"2020.01.10.902064v1.full.pdf","access_level":"open_access","date_updated":"2020-07-14T12:48:03Z","date_created":"2020-05-05T14:31:19Z","checksum":"c6799ab5daba80efe8e2ed63c15f8c81","relation":"main_file","file_id":"7801"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"7800","status":"public","title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","ddc":["570"],"month":"01","doi":"10.1101/2020.01.10.902064 ","language":[{"iso":"eng"}],"acknowledged_ssus":[{"_id":"PreCl"}],"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"oa":1,"project":[{"_id":"265CB4D0-B435-11E9-9278-68D0E5697425","grant_number":"I03600","call_identifier":"FWF","name":"Optical control of synaptic function via adhesion molecules"},{"_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24","name":"Molecular Drug Targets","call_identifier":"FWF"}],"file_date_updated":"2020-07-14T12:48:03Z","related_material":{"record":[{"id":"9429","status":"public","relation":"later_version"},{"id":"8620","status":"public","relation":"dissertation_contains"}]},"author":[{"id":"4739D480-F248-11E8-B48F-1D18A9856A87","last_name":"Morandell","first_name":"Jasmin","full_name":"Morandell, Jasmin"},{"full_name":"Schwarz, Lena A","first_name":"Lena A","last_name":"Schwarz","id":"29A8453C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Basilico","first_name":"Bernadette","orcid":"0000-0003-1843-3173","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","full_name":"Basilico, Bernadette"},{"orcid":"0000-0003-1671-393X","id":"4323B49C-F248-11E8-B48F-1D18A9856A87","last_name":"Tasciyan","first_name":"Saren","full_name":"Tasciyan, Saren"},{"full_name":"Nicolas, Armel","id":"2A103192-F248-11E8-B48F-1D18A9856A87","first_name":"Armel","last_name":"Nicolas"},{"first_name":"Christoph M","last_name":"Sommer","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0003-1216-9105","full_name":"Sommer, Christoph M"},{"last_name":"Kreuzinger","first_name":"Caroline","id":"382077BA-F248-11E8-B48F-1D18A9856A87","full_name":"Kreuzinger, Caroline"},{"full_name":"Knaus, Lisa","first_name":"Lisa","last_name":"Knaus","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87"},{"id":"D23090A2-9057-11EA-883A-A8396FC7A38F","first_name":"Zoe","last_name":"Dobler","full_name":"Dobler, Zoe"},{"full_name":"Cacci, Emanuele","last_name":"Cacci","first_name":"Emanuele"},{"full_name":"Danzl, Johann G","orcid":"0000-0001-8559-3973","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","last_name":"Danzl","first_name":"Johann G"},{"full_name":"Novarino, Gaia","first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178"}],"date_updated":"2024-03-28T23:30:14Z","date_created":"2020-05-05T14:31:33Z","year":"2020","department":[{"_id":"JoDa"},{"_id":"GaNo"},{"_id":"LifeSc"}],"publisher":"Cold Spring Harbor Laboratory","publication_status":"submitted"},{"date_published":"2020-12-01T00:00:00Z","article_type":"original","page":"126-137","publication":"Current Opinion in Genetics and Development","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","ista":"Basilico B, Morandell J, Novarino G. 2020. Molecular mechanisms for targeted ASD treatments. Current Opinion in Genetics and Development. 65(12), 126–137.","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.","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","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.","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."},"day":"01","has_accepted_license":"1","article_processing_charge":"Yes (via OA deal)","scopus_import":"1","file":[{"date_updated":"2020-07-22T06:47:45Z","date_created":"2020-07-22T06:47:45Z","success":1,"relation":"main_file","file_id":"8146","content_type":"application/pdf","file_size":1381545,"creator":"dernst","file_name":"2020_CurrentOpGenetics_Basilico.pdf","access_level":"open_access"}],"oa_version":"Published Version","status":"public","title":"Molecular mechanisms for targeted ASD treatments","ddc":["570"],"intvolume":" 65","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"8131","abstract":[{"text":"The possibility to generate construct valid animal models enabled the development and testing of therapeutic strategies targeting the core features of autism spectrum disorders (ASDs). At the same time, these studies highlighted the necessity of identifying sensitive developmental time windows for successful therapeutic interventions. Animal and human studies also uncovered the possibility to stratify the variety of ASDs in molecularly distinct subgroups, potentially facilitating effective treatment design. Here, we focus on the molecular pathways emerging as commonly affected by mutations in diverse ASD-risk genes, on their role during critical windows of brain development and the potential treatments targeting these biological processes.","lang":"eng"}],"issue":"12","type":"journal_article","language":[{"iso":"eng"}],"doi":"10.1016/j.gde.2020.06.004","quality_controlled":"1","isi":1,"project":[{"name":"ISTplus - Postdoctoral Fellowships","call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425","grant_number":"754411"},{"call_identifier":"FWF","name":"Molecular Drug Targets","grant_number":"W1232-B24","_id":"2548AE96-B435-11E9-9278-68D0E5697425"},{"name":"Neural stem cells in autism and epilepsy","_id":"05A0D778-7A3F-11EA-A408-12923DDC885E","grant_number":"F07807"}],"tmp":{"name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","short":"CC BY-NC-ND (4.0)","image":"/images/cc_by_nc_nd.png"},"oa":1,"external_id":{"pmid":["32659636"],"isi":["000598918900019"]},"month":"12","publication_identifier":{"issn":["0959437X"],"eissn":["18790380"]},"date_updated":"2024-03-28T23:30:14Z","date_created":"2020-07-19T22:00:58Z","volume":65,"author":[{"id":"36035796-5ACA-11E9-A75E-7AF2E5697425","orcid":"0000-0003-1843-3173","first_name":"Bernadette","last_name":"Basilico","full_name":"Basilico, Bernadette"},{"first_name":"Jasmin","last_name":"Morandell","id":"4739D480-F248-11E8-B48F-1D18A9856A87","full_name":"Morandell, Jasmin"},{"orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia","full_name":"Novarino, Gaia"}],"related_material":{"record":[{"id":"8620","relation":"dissertation_contains","status":"public"}]},"publication_status":"published","department":[{"_id":"GaNo"}],"publisher":"Elsevier","year":"2020","pmid":1,"file_date_updated":"2020-07-22T06:47:45Z","ec_funded":1},{"month":"01","language":[{"iso":"eng"}],"doi":"10.1038/s41431-018-0231-2","quality_controlled":"1","isi":1,"main_file_link":[{"url":"https://doi.org/10.1038/s41431-018-0231-2","open_access":"1"}],"external_id":{"isi":["000454111500019"],"pmid":["30089829"]},"oa":1,"publist_id":"7949","volume":27,"date_updated":"2023-08-24T14:28:24Z","date_created":"2018-12-11T11:44:39Z","author":[{"first_name":"Ashley","last_name":"Marsh","full_name":"Marsh, Ashley"},{"orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia","full_name":"Novarino, Gaia"},{"last_name":"Lockhart","first_name":"Paul","full_name":"Lockhart, Paul"},{"full_name":"Leventer, Richard","last_name":"Leventer","first_name":"Richard"}],"department":[{"_id":"GaNo"}],"publisher":"Springer Nature","publication_status":"published","pmid":1,"year":"2019","acknowledgement":"This work was supported by EuroGentest2 (Unit 2: “Genetic testing as part of health care”), a Coordination Action under FP7 (Grant Agreement Number 261469) and the European Society of Human Genetics. We acknowledge the participation of the patients and their families in these studies, as well as the generous financial support of the Lefroy and Handbury families. APLM was supported by an Australian Postgraduate Award. PJL is supported by an NHMRC Career Development Fellowship (GNT1032364). RJL is supported by a Melbourne Children’s Clinician Scientist Fellowship.","article_processing_charge":"No","day":"01","scopus_import":"1","date_published":"2019-01-01T00:00:00Z","page":"161-166","article_type":"original","citation":{"ama":"Marsh A, Novarino G, Lockhart P, Leventer R. CUGC for pontocerebellar hypoplasia type 9 and spastic paraplegia-63. European Journal of Human Genetics. 2019;27:161-166. doi:10.1038/s41431-018-0231-2","ieee":"A. Marsh, G. Novarino, P. Lockhart, and R. Leventer, “CUGC for pontocerebellar hypoplasia type 9 and spastic paraplegia-63,” European Journal of Human Genetics, vol. 27. Springer Nature, pp. 161–166, 2019.","apa":"Marsh, A., Novarino, G., Lockhart, P., & Leventer, R. (2019). CUGC for pontocerebellar hypoplasia type 9 and spastic paraplegia-63. European Journal of Human Genetics. Springer Nature. https://doi.org/10.1038/s41431-018-0231-2","ista":"Marsh A, Novarino G, Lockhart P, Leventer R. 2019. CUGC for pontocerebellar hypoplasia type 9 and spastic paraplegia-63. European Journal of Human Genetics. 27, 161–166.","short":"A. Marsh, G. Novarino, P. Lockhart, R. Leventer, European Journal of Human Genetics 27 (2019) 161–166.","mla":"Marsh, Ashley, et al. “CUGC for Pontocerebellar Hypoplasia Type 9 and Spastic Paraplegia-63.” European Journal of Human Genetics, vol. 27, Springer Nature, 2019, pp. 161–66, doi:10.1038/s41431-018-0231-2.","chicago":"Marsh, Ashley, Gaia Novarino, Paul Lockhart, and Richard Leventer. “CUGC for Pontocerebellar Hypoplasia Type 9 and Spastic Paraplegia-63.” European Journal of Human Genetics. Springer Nature, 2019. https://doi.org/10.1038/s41431-018-0231-2."},"publication":"European Journal of Human Genetics","abstract":[{"lang":"eng","text":"Clinical Utility Gene Card. 1. Name of Disease (Synonyms): Pontocerebellar hypoplasia type 9 (PCH9) and spastic paraplegia-63 (SPG63). 2. OMIM# of the Disease: 615809 and 615686. 3. Name of the Analysed Genes or DNA/Chromosome Segments: AMPD2 at 1p13.3. 4. OMIM# of the Gene(s): 102771."}],"type":"journal_article","oa_version":"Published Version","intvolume":" 27","title":"CUGC for pontocerebellar hypoplasia type 9 and spastic paraplegia-63","status":"public","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"105"},{"external_id":{"isi":["000460600400031"],"pmid":["30694684"]},"quality_controlled":"1","isi":1,"doi":"10.1021/acs.molpharmaceut.8b01217","language":[{"iso":"eng"}],"month":"03","year":"2019","pmid":1,"publication_status":"published","publisher":"American Chemical Society","department":[{"_id":"GaNo"}],"author":[{"full_name":"Traxl, Alexander","last_name":"Traxl","first_name":"Alexander"},{"last_name":"Mairinger","first_name":"Severin","full_name":"Mairinger, Severin"},{"full_name":"Filip, Thomas","last_name":"Filip","first_name":"Thomas"},{"last_name":"Sauberer","first_name":"Michael","full_name":"Sauberer, Michael"},{"first_name":"Johann","last_name":"Stanek","full_name":"Stanek, Johann"},{"last_name":"Poschner","first_name":"Stefan","full_name":"Poschner, Stefan"},{"last_name":"Jäger","first_name":"Walter","full_name":"Jäger, Walter"},{"full_name":"Zoufal, Viktoria","last_name":"Zoufal","first_name":"Viktoria"},{"full_name":"Novarino, Gaia","last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Tournier, Nicolas","last_name":"Tournier","first_name":"Nicolas"},{"full_name":"Bauer, Martin","first_name":"Martin","last_name":"Bauer"},{"first_name":"Thomas","last_name":"Wanek","full_name":"Wanek, Thomas"},{"full_name":"Langer, Oliver","first_name":"Oliver","last_name":"Langer"}],"date_created":"2019-03-10T22:59:19Z","date_updated":"2023-08-25T08:02:51Z","volume":16,"publication":"Molecular Pharmaceutics","citation":{"ista":"Traxl A, Mairinger S, Filip T, Sauberer M, Stanek J, Poschner S, Jäger W, Zoufal V, Novarino G, Tournier N, Bauer M, Wanek T, Langer O. 2019. Inhibition of ABCB1 and ABCG2 at the mouse blood-brain barrier with marketed drugs to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib. Molecular Pharmaceutics. 16(3), 1282–1293.","apa":"Traxl, A., Mairinger, S., Filip, T., Sauberer, M., Stanek, J., Poschner, S., … Langer, O. (2019). Inhibition of ABCB1 and ABCG2 at the mouse blood-brain barrier with marketed drugs to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib. Molecular Pharmaceutics. American Chemical Society. https://doi.org/10.1021/acs.molpharmaceut.8b01217","ieee":"A. Traxl et al., “Inhibition of ABCB1 and ABCG2 at the mouse blood-brain barrier with marketed drugs to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib,” Molecular Pharmaceutics, vol. 16, no. 3. American Chemical Society, pp. 1282–1293, 2019.","ama":"Traxl A, Mairinger S, Filip T, et al. Inhibition of ABCB1 and ABCG2 at the mouse blood-brain barrier with marketed drugs to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib. Molecular Pharmaceutics. 2019;16(3):1282-1293. doi:10.1021/acs.molpharmaceut.8b01217","chicago":"Traxl, Alexander, Severin Mairinger, Thomas Filip, Michael Sauberer, Johann Stanek, Stefan Poschner, Walter Jäger, et al. “Inhibition of ABCB1 and ABCG2 at the Mouse Blood-Brain Barrier with Marketed Drugs to Improve Brain Delivery of the Model ABCB1/ABCG2 Substrate [11C]Erlotinib.” Molecular Pharmaceutics. American Chemical Society, 2019. https://doi.org/10.1021/acs.molpharmaceut.8b01217.","mla":"Traxl, Alexander, et al. “Inhibition of ABCB1 and ABCG2 at the Mouse Blood-Brain Barrier with Marketed Drugs to Improve Brain Delivery of the Model ABCB1/ABCG2 Substrate [11C]Erlotinib.” Molecular Pharmaceutics, vol. 16, no. 3, American Chemical Society, 2019, pp. 1282–93, doi:10.1021/acs.molpharmaceut.8b01217.","short":"A. Traxl, S. Mairinger, T. Filip, M. Sauberer, J. Stanek, S. Poschner, W. Jäger, V. Zoufal, G. Novarino, N. Tournier, M. Bauer, T. Wanek, O. Langer, Molecular Pharmaceutics 16 (2019) 1282–1293."},"page":"1282-1293","date_published":"2019-03-04T00:00:00Z","scopus_import":"1","day":"04","article_processing_charge":"No","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","_id":"6088","status":"public","title":"Inhibition of ABCB1 and ABCG2 at the mouse blood-brain barrier with marketed drugs to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib","intvolume":" 16","oa_version":"None","type":"journal_article","abstract":[{"lang":"eng","text":"P-Glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) are two efflux transporters at the blood–brain barrier (BBB), which effectively restrict brain distribution of diverse drugs, such as tyrosine kinase inhibitors. There is a crucial need for pharmacological ABCB1 and ABCG2 inhibition protocols for a more effective treatment of brain diseases. In the present study, seven marketed drugs (osimertinib, erlotinib, nilotinib, imatinib, lapatinib, pazopanib, and cyclosporine A) and one nonmarketed drug (tariquidar), with known in vitro ABCB1/ABCG2 inhibitory properties, were screened for their inhibitory potency at the BBB in vivo. Positron emission tomography (PET) using the model ABCB1/ABCG2 substrate [11C]erlotinib was performed in mice. Tested inhibitors were administered as i.v. bolus injections at 30 min before the start of the PET scan, followed by a continuous i.v. infusion for the duration of the PET scan. Five of the tested drugs increased total distribution volume of [11C]erlotinib in the brain (VT,brain) compared to vehicle-treated animals (tariquidar, + 69%; erlotinib, + 19% and +23% for the 21.5 mg/kg and the 43 mg/kg dose, respectively; imatinib, + 22%; lapatinib, + 25%; and cyclosporine A, + 49%). For all drugs, increases in [11C]erlotinib brain distribution were lower than in Abcb1a/b(−/−)Abcg2(−/−) mice (+149%), which suggested that only partial ABCB1/ABCG2 inhibition was reached at the mouse BBB. The plasma concentrations of the tested drugs at the time of the PET scan were higher than clinically achievable plasma concentrations. Some of the tested drugs led to significant increases in blood radioactivity concentrations measured at the end of the PET scan (erlotinib, + 103% and +113% for the 21.5 mg/kg and the 43 mg/kg dose, respectively; imatinib, + 125%; and cyclosporine A, + 101%), which was most likely caused by decreased hepatobiliary excretion of radioactivity. Taken together, our data suggest that some marketed tyrosine kinase inhibitors may be repurposed to inhibit ABCB1 and ABCG2 at the BBB. From a clinical perspective, moderate increases in brain delivery despite the administration of high i.v. doses as well as peripheral drug–drug interactions due to transporter inhibition in clearance organs question the translatability of this concept."}],"issue":"3"},{"month":"06","publication_identifier":{"eissn":["14697793"],"issn":["00223751"]},"doi":"10.1113/JP277681","language":[{"iso":"eng"}],"external_id":{"pmid":["31006863"],"isi":["000470780400013"]},"main_file_link":[{"url":"https://doi.org/10.1113/JP277681","open_access":"1"}],"oa":1,"quality_controlled":"1","isi":1,"author":[{"full_name":"Éltes, Tímea","last_name":"Éltes","first_name":"Tímea"},{"full_name":"Szoboszlay, Miklos","first_name":"Miklos","last_name":"Szoboszlay"},{"full_name":"Szigeti, Margit Katalin","orcid":"0000-0001-9500-8758","id":"44F4BDC0-F248-11E8-B48F-1D18A9856A87","last_name":"Szigeti","first_name":"Margit Katalin"},{"full_name":"Nusser, Zoltan","last_name":"Nusser","first_name":"Zoltan"}],"date_updated":"2023-08-25T10:34:15Z","date_created":"2019-05-19T21:59:17Z","volume":597,"year":"2019","pmid":1,"publication_status":"published","department":[{"_id":"GaNo"}],"publisher":"Wiley","day":"01","article_processing_charge":"No","scopus_import":"1","date_published":"2019-06-01T00:00:00Z","publication":"Journal of Physiology","citation":{"ama":"Éltes T, Szoboszlay M, Szigeti MK, Nusser Z. Improved spike inference accuracy by estimating the peak amplitude of unitary [Ca2+] transients in weakly GCaMP6f-expressing hippocampal pyramidal cells. Journal of Physiology. 2019;597(11):2925–2947. doi:10.1113/JP277681","ista":"Éltes T, Szoboszlay M, Szigeti MK, Nusser Z. 2019. Improved spike inference accuracy by estimating the peak amplitude of unitary [Ca2+] transients in weakly GCaMP6f-expressing hippocampal pyramidal cells. Journal of Physiology. 597(11), 2925–2947.","ieee":"T. Éltes, M. Szoboszlay, M. K. Szigeti, and Z. Nusser, “Improved spike inference accuracy by estimating the peak amplitude of unitary [Ca2+] transients in weakly GCaMP6f-expressing hippocampal pyramidal cells,” Journal of Physiology, vol. 597, no. 11. Wiley, pp. 2925–2947, 2019.","apa":"Éltes, T., Szoboszlay, M., Szigeti, M. K., & Nusser, Z. (2019). Improved spike inference accuracy by estimating the peak amplitude of unitary [Ca2+] transients in weakly GCaMP6f-expressing hippocampal pyramidal cells. Journal of Physiology. Wiley. https://doi.org/10.1113/JP277681","mla":"Éltes, Tímea, et al. “Improved Spike Inference Accuracy by Estimating the Peak Amplitude of Unitary [Ca2+] Transients in Weakly GCaMP6f-Expressing Hippocampal Pyramidal Cells.” Journal of Physiology, vol. 597, no. 11, Wiley, 2019, pp. 2925–2947, doi:10.1113/JP277681.","short":"T. Éltes, M. Szoboszlay, M.K. Szigeti, Z. Nusser, Journal of Physiology 597 (2019) 2925–2947.","chicago":"Éltes, Tímea, Miklos Szoboszlay, Margit Katalin Szigeti, and Zoltan Nusser. “Improved Spike Inference Accuracy by Estimating the Peak Amplitude of Unitary [Ca2+] Transients in Weakly GCaMP6f-Expressing Hippocampal Pyramidal Cells.” Journal of Physiology. Wiley, 2019. https://doi.org/10.1113/JP277681."},"article_type":"original","page":"2925–2947","abstract":[{"text":"Investigating neuronal activity using genetically encoded Ca2+ indicators in behaving animals is hampered by inaccuracies in spike inference from fluorescent tracers. Here we combine two‐photon [Ca2+] imaging with cell‐attached recordings, followed by post hoc determination of the expression level of GCaMP6f, to explore how it affects the amplitude, kinetics and temporal summation of somatic [Ca2+] transients in mouse hippocampal pyramidal cells (PCs). The amplitude of unitary [Ca2+] transients (evoked by a single action potential) negatively correlates with GCaMP6f expression, but displays large variability even among PCs with similarly low expression levels. The summation of fluorescence signals is frequency‐dependent, supralinear and also shows remarkable cell‐to‐cell variability. We performed experimental data‐based simulations and found that spike inference error rates using MLspike depend strongly on unitary peak amplitudes and GCaMP6f expression levels. We provide simple methods for estimating the unitary [Ca2+] transients in individual weakly GCaMP6f‐expressing PCs, with which we achieve spike inference error rates of ∼5%. ","lang":"eng"}],"issue":"11","type":"journal_article","oa_version":"Published Version","_id":"6470","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","title":"Improved spike inference accuracy by estimating the peak amplitude of unitary [Ca2+] transients in weakly GCaMP6f-expressing hippocampal pyramidal cells","status":"public","intvolume":" 597"},{"publication_identifier":{"eissn":["18726240"],"issn":["00068993"]},"month":"12","external_id":{"pmid":["31521639"],"isi":["000491646600033"]},"isi":1,"quality_controlled":"1","doi":"10.1016/j.brainres.2019.146458","language":[{"iso":"eng"}],"article_number":"146458","pmid":1,"year":"2019","publisher":"Elsevier","department":[{"_id":"GaNo"}],"publication_status":"published","author":[{"full_name":"Oliveira, Bárbara","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","last_name":"Oliveira","first_name":"Bárbara"},{"id":"365A65F8-F248-11E8-B48F-1D18A9856A87","first_name":"Aysan Çerağ","last_name":"Yahya","full_name":"Yahya, Aysan Çerağ"},{"full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino"}],"volume":1724,"date_updated":"2023-08-30T06:19:49Z","date_created":"2019-09-22T22:00:35Z","scopus_import":"1","article_processing_charge":"No","day":"01","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","ista":"Oliveira B, Yahya AÇ, Novarino G. 2019. Modeling cell-cell interactions in the brain using cerebral organoids. Brain Research. 1724, 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.","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","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).","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."},"publication":"Brain Research","article_type":"original","date_published":"2019-12-01T00:00:00Z","type":"journal_article","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."}],"_id":"6896","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","intvolume":" 1724","status":"public","title":"Modeling cell-cell interactions in the brain using cerebral organoids","oa_version":"None"},{"issue":"Supplement 6","type":"journal_article","author":[{"last_name":"Morandell","first_name":"Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","full_name":"Morandell, Jasmin"},{"id":"2A103192-F248-11E8-B48F-1D18A9856A87","first_name":"Armel","last_name":"Nicolas","full_name":"Nicolas, Armel"},{"last_name":"Schwarz","first_name":"Lena A","id":"29A8453C-F248-11E8-B48F-1D18A9856A87","full_name":"Schwarz, Lena A"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino","full_name":"Novarino, Gaia"}],"volume":29,"oa_version":"None","date_created":"2020-01-30T10:07:41Z","date_updated":"2023-09-07T14:56:17Z","_id":"7415","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","year":"2019","department":[{"_id":"GaNo"},{"_id":"LifeSc"}],"intvolume":" 29","publisher":"Elsevier","publication_status":"published","title":"S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism","status":"public","article_processing_charge":"No","publication_identifier":{"issn":["0924-977X"]},"month":"12","day":"13","date_published":"2019-12-13T00:00:00Z","doi":"10.1016/j.euroneuro.2019.09.040","language":[{"iso":"eng"}],"citation":{"ieee":"J. Morandell, A. Nicolas, L. A. Schwarz, and G. Novarino, “S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism,” European Neuropsychopharmacology, vol. 29, no. Supplement 6. Elsevier, pp. S11–S12, 2019.","apa":"Morandell, J., Nicolas, A., Schwarz, L. A., & Novarino, G. (2019). S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism. European Neuropsychopharmacology. Elsevier. https://doi.org/10.1016/j.euroneuro.2019.09.040","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.","ama":"Morandell J, Nicolas A, Schwarz LA, Novarino G. S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism. European Neuropsychopharmacology. 2019;29(Supplement 6):S11-S12. doi:10.1016/j.euroneuro.2019.09.040","chicago":"Morandell, Jasmin, Armel Nicolas, Lena A Schwarz, and Gaia Novarino. “S.16.05 Illuminating the Role of the E3 Ubiquitin Ligase Cullin3 in Brain Development and Autism.” European Neuropsychopharmacology. Elsevier, 2019. https://doi.org/10.1016/j.euroneuro.2019.09.040.","short":"J. Morandell, A. Nicolas, L.A. Schwarz, G. Novarino, European Neuropsychopharmacology 29 (2019) 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."},"external_id":{"isi":["000502657500021"]},"publication":"European Neuropsychopharmacology","page":"S11-S12","quality_controlled":"1","article_type":"original","isi":1},{"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"7414","year":"2019","status":"public","publication_status":"published","title":"S.16.03 A homozygous missense mutation in SLC7A5 leads to autism spectrum disorder and microcephaly","intvolume":" 29","publisher":"Elsevier","department":[{"_id":"GaNo"}],"author":[{"last_name":"Knaus","first_name":"Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","full_name":"Knaus, Lisa"},{"id":"2ABCE612-F248-11E8-B48F-1D18A9856A87","first_name":"Dora-Clara","last_name":"Tarlungeanu","full_name":"Tarlungeanu, Dora-Clara"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino","full_name":"Novarino, Gaia"}],"date_created":"2020-01-30T10:06:15Z","date_updated":"2023-09-07T14:55:23Z","oa_version":"None","volume":29,"type":"journal_article","issue":"Supplement 6","publication":"European Neuropsychopharmacology","external_id":{"isi":["000502657500020"]},"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","ista":"Knaus L, Tarlungeanu D-C, Novarino G. 2019. S.16.03 A homozygous missense mutation in SLC7A5 leads to autism spectrum disorder and microcephaly. European Neuropsychopharmacology. 29(Supplement 6), S11.","apa":"Knaus, L., Tarlungeanu, D.-C., & Novarino, G. (2019). S.16.03 A homozygous missense mutation in SLC7A5 leads to autism spectrum disorder and microcephaly. European Neuropsychopharmacology. Elsevier. https://doi.org/10.1016/j.euroneuro.2019.09.039","ieee":"L. Knaus, D.-C. Tarlungeanu, and G. Novarino, “S.16.03 A homozygous missense mutation in SLC7A5 leads to autism spectrum disorder and microcephaly,” European Neuropsychopharmacology, vol. 29, no. Supplement 6. Elsevier, p. S11, 2019.","mla":"Knaus, Lisa, et al. “S.16.03 A Homozygous Missense Mutation in SLC7A5 Leads to Autism Spectrum Disorder and Microcephaly.” European Neuropsychopharmacology, vol. 29, no. Supplement 6, Elsevier, 2019, p. S11, doi:10.1016/j.euroneuro.2019.09.039.","short":"L. Knaus, D.-C. Tarlungeanu, G. Novarino, European Neuropsychopharmacology 29 (2019) S11.","chicago":"Knaus, Lisa, Dora-Clara Tarlungeanu, and Gaia Novarino. “S.16.03 A Homozygous Missense Mutation in SLC7A5 Leads to Autism Spectrum Disorder and Microcephaly.” European Neuropsychopharmacology. Elsevier, 2019. https://doi.org/10.1016/j.euroneuro.2019.09.039."},"quality_controlled":"1","isi":1,"article_type":"original","page":"S11","doi":"10.1016/j.euroneuro.2019.09.039","date_published":"2019-12-13T00:00:00Z","language":[{"iso":"eng"}],"day":"13","month":"12","publication_identifier":{"issn":["0924-977X"]},"article_processing_charge":"No"},{"publisher":"American Association for the Advancement of Science","intvolume":" 10","department":[{"_id":"GaNo"}],"status":"public","publication_status":"published","title":"Zika-associated microcephaly: Reduce the stress and race for the treatment","_id":"456","user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","year":"2018","volume":10,"oa_version":"None","date_created":"2018-12-11T11:46:34Z","date_updated":"2021-01-12T07:59:42Z","author":[{"last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia"}],"type":"journal_article","article_number":"eaar7514","publist_id":"7365","issue":"423","abstract":[{"lang":"eng","text":"Inhibition of the endoplasmic reticulum stress pathway may hold the key to Zika virus-associated microcephaly treatment. "}],"quality_controlled":"1","citation":{"ista":"Novarino G. 2018. Zika-associated microcephaly: Reduce the stress and race for the treatment. Science Translational Medicine. 10(423), eaar7514.","ieee":"G. Novarino, “Zika-associated microcephaly: Reduce the stress and race for the treatment,” Science Translational Medicine, vol. 10, no. 423. American Association for the Advancement of Science, 2018.","apa":"Novarino, G. (2018). Zika-associated microcephaly: Reduce the stress and race for the treatment. Science Translational Medicine. American Association for the Advancement of Science. https://doi.org/10.1126/scitranslmed.aar7514","ama":"Novarino G. Zika-associated microcephaly: Reduce the stress and race for the treatment. Science Translational Medicine. 2018;10(423). doi:10.1126/scitranslmed.aar7514","chicago":"Novarino, Gaia. “Zika-Associated Microcephaly: Reduce the Stress and Race for the Treatment.” Science Translational Medicine. American Association for the Advancement of Science, 2018. https://doi.org/10.1126/scitranslmed.aar7514.","mla":"Novarino, Gaia. “Zika-Associated Microcephaly: Reduce the Stress and Race for the Treatment.” Science Translational Medicine, vol. 10, no. 423, eaar7514, American Association for the Advancement of Science, 2018, doi:10.1126/scitranslmed.aar7514.","short":"G. Novarino, Science Translational Medicine 10 (2018)."},"publication":"Science Translational Medicine","language":[{"iso":"eng"}],"date_published":"2018-01-10T00:00:00Z","doi":"10.1126/scitranslmed.aar7514","scopus_import":1,"day":"10","month":"01"},{"scopus_import":"1","day":"07","has_accepted_license":"1","article_processing_charge":"No","publication":"Experimental & Molecular Medicine","citation":{"ama":"Tarlungeanu D-C, Novarino G. Genomics in neurodevelopmental disorders: an avenue to personalized medicine. Experimental & Molecular Medicine. 2018;50(8). doi:10.1038/s12276-018-0129-7","ista":"Tarlungeanu D-C, Novarino G. 2018. Genomics in neurodevelopmental disorders: an avenue to personalized medicine. Experimental & Molecular Medicine. 50(8), 100.","apa":"Tarlungeanu, D.-C., & Novarino, G. (2018). Genomics in neurodevelopmental disorders: an avenue to personalized medicine. Experimental & Molecular Medicine. Springer Nature. https://doi.org/10.1038/s12276-018-0129-7","ieee":"D.-C. Tarlungeanu and G. Novarino, “Genomics in neurodevelopmental disorders: an avenue to personalized medicine,” Experimental & Molecular Medicine, vol. 50, no. 8. Springer Nature, 2018.","mla":"Tarlungeanu, Dora-Clara, and Gaia Novarino. “Genomics in Neurodevelopmental Disorders: An Avenue to Personalized Medicine.” Experimental & Molecular Medicine, vol. 50, no. 8, 100, Springer Nature, 2018, doi:10.1038/s12276-018-0129-7.","short":"D.-C. Tarlungeanu, G. Novarino, Experimental & Molecular Medicine 50 (2018).","chicago":"Tarlungeanu, Dora-Clara, and Gaia Novarino. “Genomics in Neurodevelopmental Disorders: An Avenue to Personalized Medicine.” Experimental & Molecular Medicine. Springer Nature, 2018. https://doi.org/10.1038/s12276-018-0129-7."},"date_published":"2018-08-07T00:00:00Z","type":"journal_article","abstract":[{"lang":"eng","text":"Despite the remarkable number of scientific breakthroughs of the last 100 years, the treatment of neurodevelopmental\r\ndisorders (e.g., autism spectrum disorder, intellectual disability) remains a great challenge. Recent advancements in\r\ngenomics, such as whole-exome or whole-genome sequencing, have enabled scientists to identify numerous\r\nmutations underlying neurodevelopmental disorders. Given the few hundred risk genes that have been discovered,\r\nthe etiological variability and the heterogeneous clinical presentation, the need for genotype — along with phenotype-\r\nbased diagnosis of individual patients has become a requisite. In this review we look at recent advancements in\r\ngenomic analysis and their translation into clinical practice."}],"issue":"8","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"5888","status":"public","title":"Genomics in neurodevelopmental disorders: an avenue to personalized medicine","ddc":["570"],"intvolume":" 50","oa_version":"Published Version","file":[{"content_type":"application/pdf","file_size":1237482,"creator":"dernst","access_level":"open_access","file_name":"2018_EMM_Tarlungeanu.pdf","checksum":"4498301c8c53097c9a1a8ef990936eb5","date_updated":"2020-07-14T12:47:13Z","date_created":"2019-01-28T15:18:02Z","relation":"main_file","file_id":"5893"}],"month":"08","publication_identifier":{"issn":["2092-6413"]},"external_id":{"isi":["000441266700006"],"pmid":["30089840"]},"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"isi":1,"quality_controlled":"1","doi":"10.1038/s12276-018-0129-7","language":[{"iso":"eng"}],"article_number":"100","file_date_updated":"2020-07-14T12:47:13Z","year":"2018","pmid":1,"publication_status":"published","publisher":"Springer Nature","department":[{"_id":"GaNo"}],"author":[{"first_name":"Dora-Clara","last_name":"Tarlungeanu","id":"2ABCE612-F248-11E8-B48F-1D18A9856A87","full_name":"Tarlungeanu, Dora-Clara"},{"orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia","full_name":"Novarino, Gaia"}],"date_updated":"2023-09-11T14:04:41Z","date_created":"2019-01-27T22:59:11Z","volume":50},{"doi":"10.1016/j.conb.2017.12.005","language":[{"iso":"eng"}],"external_id":{"isi":["000427101600018"]},"isi":1,"quality_controlled":"1","month":"02","author":[{"full_name":"Sacco, Roberto","id":"42C9F57E-F248-11E8-B48F-1D18A9856A87","first_name":"Roberto","last_name":"Sacco"},{"full_name":"Cacci, Emanuele","first_name":"Emanuele","last_name":"Cacci"},{"full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino"}],"date_created":"2018-12-11T11:47:06Z","date_updated":"2023-09-13T09:01:56Z","volume":48,"year":"2018","publication_status":"published","publisher":"Elsevier","department":[{"_id":"GaNo"}],"publist_id":"7268","date_published":"2018-02-01T00:00:00Z","publication":"Current Opinion in Neurobiology","citation":{"ista":"Sacco R, Cacci E, Novarino G. 2018. Neural stem cells in neuropsychiatric disorders. Current Opinion in Neurobiology. 48(2), 131–138.","ieee":"R. Sacco, E. Cacci, and G. Novarino, “Neural stem cells in neuropsychiatric disorders,” Current Opinion in Neurobiology, vol. 48, no. 2. Elsevier, pp. 131–138, 2018.","apa":"Sacco, R., Cacci, E., & Novarino, G. (2018). Neural stem cells in neuropsychiatric disorders. Current Opinion in Neurobiology. Elsevier. https://doi.org/10.1016/j.conb.2017.12.005","ama":"Sacco R, Cacci E, Novarino G. Neural stem cells in neuropsychiatric disorders. Current Opinion in Neurobiology. 2018;48(2):131-138. doi:10.1016/j.conb.2017.12.005","chicago":"Sacco, Roberto, Emanuele Cacci, and Gaia Novarino. “Neural Stem Cells in Neuropsychiatric Disorders.” Current Opinion in Neurobiology. Elsevier, 2018. https://doi.org/10.1016/j.conb.2017.12.005.","mla":"Sacco, Roberto, et al. “Neural Stem Cells in Neuropsychiatric Disorders.” Current Opinion in Neurobiology, vol. 48, no. 2, Elsevier, 2018, pp. 131–38, doi:10.1016/j.conb.2017.12.005.","short":"R. Sacco, E. Cacci, G. Novarino, Current Opinion in Neurobiology 48 (2018) 131–138."},"page":"131 - 138","day":"01","article_processing_charge":"No","scopus_import":"1","oa_version":"None","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","_id":"546","status":"public","title":"Neural stem cells in neuropsychiatric disorders","intvolume":" 48","abstract":[{"lang":"eng","text":"The precise control of neural stem cell (NSC) proliferation and differentiation is crucial for the development and function of the human brain. Here, we review the emerging links between the alteration of embryonic and adult neurogenesis and the etiology of neuropsychiatric disorders (NPDs) such as autism spectrum disorders (ASDs) and schizophrenia (SCZ), as well as the advances in stem cell-based modeling and the novel therapeutic targets derived from these studies."}],"issue":"2","type":"journal_article"},{"intvolume":" 55","status":"public","title":"A homozygous founder mutation in TRAPPC6B associates with a neurodevelopmental disorder characterised by microcephaly epilepsy and autistic features","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"691","oa_version":"Submitted Version","type":"journal_article","issue":"1","abstract":[{"text":"Background: Transport protein particle (TRAPP) is a multisubunit complex that regulates membrane trafficking through the Golgi apparatus. The clinical phenotype associated with mutations in various TRAPP subunits has allowed elucidation of their functions in specific tissues. The role of some subunits in human disease, however, has not been fully established, and their functions remain uncertain.\r\n\r\nObjective: We aimed to expand the range of neurodevelopmental disorders associated with mutations in TRAPP subunits by exome sequencing of consanguineous families.\r\n\r\nMethods: Linkage and homozygosity mapping and candidate gene analysis were used to identify homozygous mutations in families. Patient fibroblasts were used to study splicing defect and zebrafish to model the disease.\r\n\r\nResults: We identified six individuals from three unrelated families with a founder homozygous splice mutation in TRAPPC6B, encoding a core subunit of the complex TRAPP I. Patients manifested a neurodevelopmental disorder characterised by microcephaly, epilepsy and autistic features, and showed splicing defect. Zebrafish trappc6b morphants replicated the human phenotype, displaying decreased head size and neuronal hyperexcitability, leading to a lower seizure threshold.\r\n\r\nConclusion: This study provides clinical and functional evidence of the role of TRAPPC6B in brain development and function.","lang":"eng"}],"page":"48 - 54","article_type":"original","citation":{"apa":"Marin Valencia, I., Novarino, G., Johansen, A., Rosti, B., Issa, M., Musaev, D., … Gleeson, J. (2018). A homozygous founder mutation in TRAPPC6B associates with a neurodevelopmental disorder characterised by microcephaly epilepsy and autistic features. Journal of Medical Genetics. BMJ Publishing Group. https://doi.org/10.1136/jmedgenet-2017-104627","ieee":"I. Marin Valencia et al., “A homozygous founder mutation in TRAPPC6B associates with a neurodevelopmental disorder characterised by microcephaly epilepsy and autistic features,” Journal of Medical Genetics, vol. 55, no. 1. BMJ Publishing Group, pp. 48–54, 2018.","ista":"Marin Valencia I, Novarino G, Johansen A, Rosti B, Issa M, Musaev D, Bhat G, Scott E, Silhavy J, Stanley V, Rosti R, Gleeson J, Imam F, Zaki M, Gleeson J. 2018. A homozygous founder mutation in TRAPPC6B associates with a neurodevelopmental disorder characterised by microcephaly epilepsy and autistic features. Journal of Medical Genetics. 55(1), 48–54.","ama":"Marin Valencia I, Novarino G, Johansen A, et al. A homozygous founder mutation in TRAPPC6B associates with a neurodevelopmental disorder characterised by microcephaly epilepsy and autistic features. Journal of Medical Genetics. 2018;55(1):48-54. doi:10.1136/jmedgenet-2017-104627","chicago":"Marin Valencia, Isaac, Gaia Novarino, Anide Johansen, Başak Rosti, Mahmoud Issa, Damir Musaev, Gifty Bhat, et al. “A Homozygous Founder Mutation in TRAPPC6B Associates with a Neurodevelopmental Disorder Characterised by Microcephaly Epilepsy and Autistic Features.” Journal of Medical Genetics. BMJ Publishing Group, 2018. https://doi.org/10.1136/jmedgenet-2017-104627.","short":"I. Marin Valencia, G. Novarino, A. Johansen, B. Rosti, M. Issa, D. Musaev, G. Bhat, E. Scott, J. Silhavy, V. Stanley, R. Rosti, J. Gleeson, F. Imam, M. Zaki, J. Gleeson, Journal of Medical Genetics 55 (2018) 48–54.","mla":"Marin Valencia, Isaac, et al. “A Homozygous Founder Mutation in TRAPPC6B Associates with a Neurodevelopmental Disorder Characterised by Microcephaly Epilepsy and Autistic Features.” Journal of Medical Genetics, vol. 55, no. 1, BMJ Publishing Group, 2018, pp. 48–54, doi:10.1136/jmedgenet-2017-104627."},"publication":"Journal of Medical Genetics","date_published":"2018-01-01T00:00:00Z","scopus_import":"1","article_processing_charge":"No","day":"01","department":[{"_id":"GaNo"}],"publisher":"BMJ Publishing Group","publication_status":"published","pmid":1,"year":"2018","volume":55,"date_updated":"2023-10-16T09:55:43Z","date_created":"2018-12-11T11:47:57Z","author":[{"last_name":"Marin Valencia","first_name":"Isaac","full_name":"Marin Valencia, Isaac"},{"last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia"},{"full_name":"Johansen, Anide","first_name":"Anide","last_name":"Johansen"},{"full_name":"Rosti, Başak","first_name":"Başak","last_name":"Rosti"},{"first_name":"Mahmoud","last_name":"Issa","full_name":"Issa, Mahmoud"},{"full_name":"Musaev, Damir","last_name":"Musaev","first_name":"Damir"},{"full_name":"Bhat, Gifty","first_name":"Gifty","last_name":"Bhat"},{"last_name":"Scott","first_name":"Eric","full_name":"Scott, Eric"},{"last_name":"Silhavy","first_name":"Jennifer","full_name":"Silhavy, Jennifer"},{"last_name":"Stanley","first_name":"Valentina","full_name":"Stanley, Valentina"},{"full_name":"Rosti, Rasim","first_name":"Rasim","last_name":"Rosti"},{"last_name":"Gleeson","first_name":"Jeremy","full_name":"Gleeson, Jeremy"},{"first_name":"Farhad","last_name":"Imam","full_name":"Imam, Farhad"},{"full_name":"Zaki, Maha","last_name":"Zaki","first_name":"Maha"},{"full_name":"Gleeson, Joseph","last_name":"Gleeson","first_name":"Joseph"}],"publist_id":"7016","project":[{"name":"Probing development and reversibility of autism spectrum disorders","_id":"254BA948-B435-11E9-9278-68D0E5697425","grant_number":"401299"}],"quality_controlled":"1","isi":1,"main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056005/","open_access":"1"}],"external_id":{"isi":["000418199800007"],"pmid":["28626029"]},"oa":1,"language":[{"iso":"eng"}],"doi":"10.1136/jmedgenet-2017-104627","publication_identifier":{"issn":["0022-2593"]},"month":"01"},{"has_accepted_license":"1","article_processing_charge":"No","day":"01","date_published":"2018-03-01T00:00:00Z","page":"88","citation":{"ama":"Tarlungeanu D-C. The branched chain amino acids in autism spectrum disorders . 2018. doi:10.15479/AT:ISTA:th_992","ista":"Tarlungeanu D-C. 2018. The branched chain amino acids in autism spectrum disorders . Institute of Science and Technology Austria.","apa":"Tarlungeanu, D.-C. (2018). The branched chain amino acids in autism spectrum disorders . Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_992","ieee":"D.-C. Tarlungeanu, “The branched chain amino acids in autism spectrum disorders ,” Institute of Science and Technology Austria, 2018.","mla":"Tarlungeanu, Dora-Clara. The Branched Chain Amino Acids in Autism Spectrum Disorders . Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th_992.","short":"D.-C. Tarlungeanu, The Branched Chain Amino Acids in Autism Spectrum Disorders , Institute of Science and Technology Austria, 2018.","chicago":"Tarlungeanu, Dora-Clara. “The Branched Chain Amino Acids in Autism Spectrum Disorders .” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th_992."},"abstract":[{"lang":"eng","text":"Autism spectrum disorders (ASD) are a group of genetic disorders often overlapping with other neurological conditions. Despite the remarkable number of scientific breakthroughs of the last 100 years, the treatment of neurodevelopmental disorders (e.g. autism spectrum disorder, intellectual disability, epilepsy) remains a great challenge. Recent advancements in geno mics, like whole-exome or whole-genome sequencing, have enabled scientists to identify numerous mutations underlying neurodevelopmental disorders. Given the few hundred risk genes that were discovered, the etiological variability and the heterogeneous phenotypic outcomes, the need for genotype -along with phenotype- based diagnosis of individual patients becomes a requisite. Driven by this rationale, in a previous study our group described mutations, identified via whole - exome sequencing, in the gene BCKDK – encoding for a key regulator of branched chain amin o acid (BCAA) catabolism - as a cause of ASD. Following up on the role of BCAAs, in the study described here we show that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid transporter localized mainly at the blood brain barrier (BBB), has an essential role in maintaining normal levels of brain BCAAs. In mice, deletion of Slc7a5 from the endothelial cells of the BBB leads to atypical brain amino acid profile, abnormal mRNA translation and severe neurolo gical abnormalities. Additionally, deletion of Slc7a5 from the neural progenitor cell population leads to microcephaly. Interestingly, we demonstrate that BCAA intracerebroventricular administration ameliorates abnormal behaviors in adult mutant mice. Furthermore, whole - exome sequencing of patients diagnosed with neurological dis o r ders helped us identify several patients with autistic traits, microcephaly and motor delay carrying deleterious homozygous mutations in the SLC7A5 gene. In conclusion, our data elucidate a neurological syndrome defined by SLC7A5 mutations and support an essential role for t he BCAA s in human bra in function. Together with r ecent studies (described in chapter two) that have successfully made the transition into clinical practice, our findings on the role of B CAAs might have a crucial impact on the development of novel individualized therapeutic strategies for ASD. 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","status":"public","ddc":["570","616"],"_id":"395","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","publication_identifier":{"issn":["2663-337X"]},"month":"03","language":[{"iso":"eng"}],"degree_awarded":"PhD","supervisor":[{"orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia","full_name":"Novarino, Gaia"}],"acknowledged_ssus":[{"_id":"PreCl"},{"_id":"EM-Fac"},{"_id":"Bio"}],"doi":"10.15479/AT:ISTA:th_992","project":[{"name":"Transmembrane Transporters in Health and Disease","call_identifier":"FWF","_id":"25473368-B435-11E9-9278-68D0E5697425","grant_number":"F03523"}],"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY 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Alena"},{"id":"3065DFC4-F248-11E8-B48F-1D18A9856A87","first_name":"Kasumi","last_name":"Kishi","full_name":"Kishi, Kasumi"},{"full_name":"Chiaradia, Ilaria","orcid":"0000-0002-9529-4464","id":"B6467F20-02D0-11E9-BDA5-E960C241894A","last_name":"Chiaradia","first_name":"Ilaria"},{"first_name":"Kyung","last_name":"Noh","full_name":"Noh, Kyung"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino","full_name":"Novarino, Gaia"}],"related_material":{"record":[{"id":"6074","status":"public","relation":"popular_science"},{"id":"12364","relation":"dissertation_contains","status":"public"}],"link":[{"url":"https://ist.ac.at/en/news/mutation-that-causes-autism-and-intellectual-disability-makes-brain-less-flexible/","relation":"press_release","description":"News on IST Homepage"}]},"date_created":"2018-12-11T11:44:05Z","date_updated":"2024-03-28T23:30:45Z","volume":21,"year":"2018","acknowledgement":"This work was supported by the Simons Foundation Autism Research Initiative (grant 401299) to G.N. and the DFG (SPP1738 grant NO 1249) to K.-M.N.","publication_status":"published","publisher":"Nature Publishing Group","department":[{"_id":"GaNo"},{"_id":"EdHa"}],"day":"19","has_accepted_license":"1","article_processing_charge":"No","scopus_import":"1","date_published":"2018-11-19T00:00:00Z","publication":"Nature Neuroscience","citation":{"ista":"Deliu E, Arecco N, Morandell J, Dotter C, Contreras X, Girardot C, Käsper E, Kozlova A, Kishi K, Chiaradia I, Noh K, Novarino G. 2018. Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition. Nature Neuroscience. 21(12), 1717–1727.","ieee":"E. Deliu et al., “Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition,” Nature Neuroscience, vol. 21, no. 12. Nature Publishing Group, pp. 1717–1727, 2018.","apa":"Deliu, E., Arecco, N., Morandell, J., Dotter, C., Contreras, X., Girardot, C., … Novarino, G. (2018). Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition. Nature Neuroscience. Nature Publishing Group. https://doi.org/10.1038/s41593-018-0266-2","ama":"Deliu E, Arecco N, Morandell J, et al. Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition. Nature Neuroscience. 2018;21(12):1717-1727. doi:10.1038/s41593-018-0266-2","chicago":"Deliu, Elena, Niccoló Arecco, Jasmin Morandell, Christoph Dotter, Ximena Contreras, Charles Girardot, Eva Käsper, et al. “Haploinsufficiency of the Intellectual Disability Gene SETD5 Disturbs Developmental Gene Expression and Cognition.” Nature Neuroscience. Nature Publishing Group, 2018. https://doi.org/10.1038/s41593-018-0266-2.","mla":"Deliu, Elena, et al. “Haploinsufficiency of the Intellectual Disability Gene SETD5 Disturbs Developmental Gene Expression and Cognition.” Nature Neuroscience, vol. 21, no. 12, Nature Publishing Group, 2018, pp. 1717–27, doi:10.1038/s41593-018-0266-2.","short":"E. Deliu, N. Arecco, J. Morandell, C. Dotter, X. Contreras, C. Girardot, E. Käsper, A. Kozlova, K. Kishi, I. Chiaradia, K. Noh, G. Novarino, Nature Neuroscience 21 (2018) 1717–1727."},"article_type":"original","page":"1717 - 1727","abstract":[{"lang":"eng","text":"SETD5 gene mutations have been identified as a frequent cause of idiopathic intellectual disability. Here we show that Setd5-haploinsufficient mice present developmental defects such as abnormal brain-to-body weight ratios and neural crest defect-associated phenotypes. Furthermore, Setd5-mutant mice show impairments in cognitive tasks, enhanced long-term potentiation, delayed ontogenetic profile of ultrasonic vocalization, and behavioral inflexibility. Behavioral issues are accompanied by abnormal expression of postsynaptic density proteins previously associated with cognition. Our data additionally indicate that Setd5 regulates RNA polymerase II dynamics and gene transcription via its interaction with the Hdac3 and Paf1 complexes, findings potentially explaining the gene expression defects observed in Setd5-haploinsufficient mice. Our results emphasize the decisive role of Setd5 in a biological pathway found to be disrupted in humans with intellectual disability and autism spectrum disorder."}],"issue":"12","type":"journal_article","pubrep_id":"1071","file":[{"access_level":"open_access","file_name":"2017_NatureNeuroscience_Deliu.pdf","file_size":8167169,"content_type":"application/pdf","creator":"dernst","relation":"main_file","file_id":"6255","checksum":"60abd0f05b7cdc08a6b0ec460884084f","date_created":"2019-04-09T07:41:57Z","date_updated":"2020-07-14T12:45:58Z"}],"oa_version":"Submitted Version","_id":"3","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","status":"public","title":"Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition","ddc":["570"],"intvolume":" 21"},{"author":[{"full_name":"Khamina, Kseniya","first_name":"Kseniya","last_name":"Khamina"},{"full_name":"Lercher, Alexander","last_name":"Lercher","first_name":"Alexander"},{"first_name":"Michael","last_name":"Caldera","full_name":"Caldera, Michael"},{"last_name":"Schliehe","first_name":"Christopher","full_name":"Schliehe, Christopher"},{"full_name":"Vilagos, Bojan","first_name":"Bojan","last_name":"Vilagos"},{"last_name":"Sahin","first_name":"Mehmet","full_name":"Sahin, Mehmet"},{"full_name":"Kosack, Lindsay","first_name":"Lindsay","last_name":"Kosack"},{"last_name":"Bhattacharya","first_name":"Anannya","full_name":"Bhattacharya, Anannya"},{"last_name":"Májek","first_name":"Peter","full_name":"Májek, Peter"},{"last_name":"Stukalov","first_name":"Alexey","full_name":"Stukalov, Alexey"},{"id":"42C9F57E-F248-11E8-B48F-1D18A9856A87","first_name":"Roberto","last_name":"Sacco","full_name":"Sacco, Roberto"},{"first_name":"Leo","last_name":"James","full_name":"James, Leo"},{"first_name":"Daniel","last_name":"Pinschewer","full_name":"Pinschewer, Daniel"},{"full_name":"Bennett, Keiryn","last_name":"Bennett","first_name":"Keiryn"},{"last_name":"Menche","first_name":"Jörg","full_name":"Menche, Jörg"},{"last_name":"Bergthaler","first_name":"Andreas","full_name":"Bergthaler, Andreas"}],"date_created":"2018-12-11T11:47:03Z","date_updated":"2021-01-12T08:01:48Z","volume":13,"year":"2017","publication_status":"published","publisher":"Public Library of Science","department":[{"_id":"GaNo"}],"file_date_updated":"2020-07-14T12:46:44Z","publist_id":"7276","article_number":"e1006758","doi":"10.1371/journal.ppat.1006758","language":[{"iso":"eng"}],"oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"quality_controlled":"1","month":"12","publication_identifier":{"issn":["15537366"]},"pubrep_id":"931","oa_version":"Published Version","file":[{"creator":"system","file_size":4106772,"content_type":"application/pdf","file_name":"IST-2018-931-v1+1_journal.ppat.1006758.pdf","access_level":"open_access","date_updated":"2020-07-14T12:46:44Z","date_created":"2018-12-12T10:12:26Z","checksum":"1aa20f19a1e90664fadce6e7d5284fdc","file_id":"4944","relation":"main_file"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"540","title":"Characterization of host proteins interacting with the lymphocytic choriomeningitis virus L protein","ddc":["576","616"],"status":"public","intvolume":" 13","abstract":[{"text":"RNA-dependent RNA polymerases (RdRps) play a key role in the life cycle of RNA viruses and impact their immunobiology. The arenavirus lymphocytic choriomeningitis virus (LCMV) strain Clone 13 provides a benchmark model for studying chronic infection. A major genetic determinant for its ability to persist maps to a single amino acid exchange in the viral L protein, which exhibits RdRp activity, yet its functional consequences remain elusive. To unravel the L protein interactions with the host proteome, we engineered infectious L protein-tagged LCMV virions by reverse genetics. A subsequent mass-spectrometric analysis of L protein pulldowns from infected human cells revealed a comprehensive network of interacting host proteins. The obtained LCMV L protein interactome was bioinformatically integrated with known host protein interactors of RdRps from other RNA viruses, emphasizing interconnected modules of human proteins. Functional characterization of selected interactors highlighted proviral (DDX3X) as well as antiviral (NKRF, TRIM21) host factors. To corroborate these findings, we infected Trim21-/-mice with LCMV and found impaired virus control in chronic infection. These results provide insights into the complex interactions of the arenavirus LCMV and other viral RdRps with the host proteome and contribute to a better molecular understanding of how chronic viruses interact with their host.","lang":"eng"}],"issue":"12","type":"journal_article","date_published":"2017-12-01T00:00:00Z","publication":"PLoS Pathogens","citation":{"ista":"Khamina K, Lercher A, Caldera M, Schliehe C, Vilagos B, Sahin M, Kosack L, Bhattacharya A, Májek P, Stukalov A, Sacco R, James L, Pinschewer D, Bennett K, Menche J, Bergthaler A. 2017. Characterization of host proteins interacting with the lymphocytic choriomeningitis virus L protein. PLoS Pathogens. 13(12), e1006758.","apa":"Khamina, K., Lercher, A., Caldera, M., Schliehe, C., Vilagos, B., Sahin, M., … Bergthaler, A. (2017). Characterization of host proteins interacting with the lymphocytic choriomeningitis virus L protein. PLoS Pathogens. Public Library of Science. https://doi.org/10.1371/journal.ppat.1006758","ieee":"K. Khamina et al., “Characterization of host proteins interacting with the lymphocytic choriomeningitis virus L protein,” PLoS Pathogens, vol. 13, no. 12. Public Library of Science, 2017.","ama":"Khamina K, Lercher A, Caldera M, et al. Characterization of host proteins interacting with the lymphocytic choriomeningitis virus L protein. PLoS Pathogens. 2017;13(12). doi:10.1371/journal.ppat.1006758","chicago":"Khamina, Kseniya, Alexander Lercher, Michael Caldera, Christopher Schliehe, Bojan Vilagos, Mehmet Sahin, Lindsay Kosack, et al. “Characterization of Host Proteins Interacting with the Lymphocytic Choriomeningitis Virus L Protein.” PLoS Pathogens. Public Library of Science, 2017. https://doi.org/10.1371/journal.ppat.1006758.","mla":"Khamina, Kseniya, et al. “Characterization of Host Proteins Interacting with the Lymphocytic Choriomeningitis Virus L Protein.” PLoS Pathogens, vol. 13, no. 12, e1006758, Public Library of Science, 2017, doi:10.1371/journal.ppat.1006758.","short":"K. Khamina, A. Lercher, M. Caldera, C. Schliehe, B. Vilagos, M. Sahin, L. Kosack, A. Bhattacharya, P. Májek, A. Stukalov, R. Sacco, L. James, D. Pinschewer, K. Bennett, J. Menche, A. Bergthaler, PLoS Pathogens 13 (2017)."},"day":"01","has_accepted_license":"1","scopus_import":1},{"quality_controlled":"1","language":[{"iso":"eng"}],"doi":"10.1007/978-3-319-52498-6_9","month":"05","publication_identifier":{"isbn":["978-3-319-52496-2"],"issn":["03015556"]},"publication_status":"published","editor":[{"full_name":"Schmeisser, Michael","first_name":"Michael","last_name":"Schmeisser"},{"full_name":"Boekers, Tobias","first_name":"Tobias","last_name":"Boekers"}],"department":[{"_id":"GaNo"}],"publisher":"Springer","year":"2017","date_updated":"2021-01-12T08:06:46Z","date_created":"2018-12-11T11:47:33Z","volume":224,"author":[{"last_name":"Hill Yardin","first_name":"Elisa","full_name":"Hill Yardin, Elisa"},{"first_name":"Sonja","last_name":"Mckeown","full_name":"Mckeown, Sonja"},{"full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia"},{"full_name":"Grabrucker, Andreas","first_name":"Andreas","last_name":"Grabrucker"}],"publist_id":"7177","page":"159 - 187","publication":"Translational Anatomy and Cell Biology of Autism Spectrum Disorder","citation":{"short":"E. Hill Yardin, S. Mckeown, G. Novarino, A. Grabrucker, in:, M. Schmeisser, T. Boekers (Eds.), Translational Anatomy and Cell Biology of Autism Spectrum Disorder, Springer, 2017, pp. 159–187.","mla":"Hill Yardin, Elisa, et al. “Extracerebral Dysfunction in Animal Models of Autism Spectrum Disorder.” Translational Anatomy and Cell Biology of Autism Spectrum Disorder, edited by Michael Schmeisser and Tobias Boekers, vol. 224, Springer, 2017, pp. 159–87, doi:10.1007/978-3-319-52498-6_9.","chicago":"Hill Yardin, Elisa, Sonja Mckeown, Gaia Novarino, and Andreas Grabrucker. “Extracerebral Dysfunction in Animal Models of Autism Spectrum Disorder.” In Translational Anatomy and Cell Biology of Autism Spectrum Disorder, edited by Michael Schmeisser and Tobias Boekers, 224:159–87. Advances in Anatomy Embryology and Cell Biology. Springer, 2017. https://doi.org/10.1007/978-3-319-52498-6_9.","ama":"Hill Yardin E, Mckeown S, Novarino G, Grabrucker A. Extracerebral dysfunction in animal models of autism spectrum disorder. In: Schmeisser M, Boekers T, eds. Translational Anatomy and Cell Biology of Autism Spectrum Disorder. Vol 224. Advances in Anatomy Embryology and Cell Biology. Springer; 2017:159-187. doi:10.1007/978-3-319-52498-6_9","apa":"Hill Yardin, E., Mckeown, S., Novarino, G., & Grabrucker, A. (2017). Extracerebral dysfunction in animal models of autism spectrum disorder. In M. Schmeisser & T. Boekers (Eds.), Translational Anatomy and Cell Biology of Autism Spectrum Disorder (Vol. 224, pp. 159–187). Springer. https://doi.org/10.1007/978-3-319-52498-6_9","ieee":"E. Hill Yardin, S. Mckeown, G. Novarino, and A. Grabrucker, “Extracerebral dysfunction in animal models of autism spectrum disorder,” in Translational Anatomy and Cell Biology of Autism Spectrum Disorder, vol. 224, M. Schmeisser and T. Boekers, Eds. Springer, 2017, pp. 159–187.","ista":"Hill Yardin E, Mckeown S, Novarino G, Grabrucker A. 2017.Extracerebral dysfunction in animal models of autism spectrum disorder. In: Translational Anatomy and Cell Biology of Autism Spectrum Disorder. ADVSANAT, vol. 224, 159–187."},"date_published":"2017-05-28T00:00:00Z","series_title":"Advances in Anatomy Embryology and Cell Biology","scopus_import":1,"day":"28","title":"Extracerebral dysfunction in animal models of autism spectrum disorder","status":"public","intvolume":" 224","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"623","oa_version":"None","alternative_title":["ADVSANAT"],"type":"book_chapter","abstract":[{"lang":"eng","text":"Genetic factors might be largely responsible for the development of autism spectrum disorder (ASD) that alone or in combination with specific environmental risk factors trigger the pathology. Multiple mutations identified in ASD patients that impair synaptic function in the central nervous system are well studied in animal models. How these mutations might interact with other risk factors is not fully understood though. Additionally, how systems outside of the brain are altered in the context of ASD is an emerging area of research. Extracerebral influences on the physiology could begin in utero and contribute to changes in the brain and in the development of other body systems and further lead to epigenetic changes. Therefore, multiple recent studies have aimed at elucidating the role of gene-environment interactions in ASD. Here we provide an overview on the extracerebral systems that might play an important associative role in ASD and review evidence regarding the potential roles of inflammation, trace metals, metabolism, genetic susceptibility, enteric nervous system function and the microbiota of the gastrointestinal (GI) tract on the development of endophenotypes in animal models of ASD. By influencing environmental conditions, it might be possible to reduce or limit the severity of ASD pathology."}]},{"page":"189 - 211","citation":{"short":"J. Schroeder, E. Deliu, G. Novarino, M. Schmeisser, in:, M. Schmeisser, T. Boekers (Eds.), Translational Anatomy and Cell Biology of Autism Spectrum Disorder, Springer, 2017, pp. 189–211.","mla":"Schroeder, Jan, et al. “Genetic and Pharmacological Reversibility of Phenotypes in Mouse Models of Autism Spectrum Disorder.” Translational Anatomy and Cell Biology of Autism Spectrum Disorder, edited by Michael Schmeisser and Tobias Boekers, vol. 224, Springer, 2017, pp. 189–211, doi:10.1007/978-3-319-52498-6_10.","chicago":"Schroeder, Jan, Elena Deliu, Gaia Novarino, and Michael Schmeisser. “Genetic and Pharmacological Reversibility of Phenotypes in Mouse Models of Autism Spectrum Disorder.” In Translational Anatomy and Cell Biology of Autism Spectrum Disorder, edited by Michael Schmeisser and Tobias Boekers, 224:189–211. Advances in Anatomy Embryology and Cell Biology. Springer, 2017. https://doi.org/10.1007/978-3-319-52498-6_10.","ama":"Schroeder J, Deliu E, Novarino G, Schmeisser M. Genetic and pharmacological reversibility of phenotypes in mouse models of autism spectrum disorder. In: Schmeisser M, Boekers T, eds. Translational Anatomy and Cell Biology of Autism Spectrum Disorder. Vol 224. Advances in Anatomy Embryology and Cell Biology. Springer; 2017:189-211. doi:10.1007/978-3-319-52498-6_10","apa":"Schroeder, J., Deliu, E., Novarino, G., & Schmeisser, M. (2017). Genetic and pharmacological reversibility of phenotypes in mouse models of autism spectrum disorder. In M. Schmeisser & T. Boekers (Eds.), Translational Anatomy and Cell Biology of Autism Spectrum Disorder (Vol. 224, pp. 189–211). Springer. https://doi.org/10.1007/978-3-319-52498-6_10","ieee":"J. Schroeder, E. Deliu, G. Novarino, and M. Schmeisser, “Genetic and pharmacological reversibility of phenotypes in mouse models of autism spectrum disorder,” in Translational Anatomy and Cell Biology of Autism Spectrum Disorder, vol. 224, M. Schmeisser and T. Boekers, Eds. Springer, 2017, pp. 189–211.","ista":"Schroeder J, Deliu E, Novarino G, Schmeisser M. 2017.Genetic and pharmacological reversibility of phenotypes in mouse models of autism spectrum disorder. In: Translational Anatomy and Cell Biology of Autism Spectrum Disorder. ADVSANAT, vol. 224, 189–211."},"publication":"Translational Anatomy and Cell Biology of Autism Spectrum Disorder","date_published":"2017-05-28T00:00:00Z","series_title":"Advances in Anatomy Embryology and Cell Biology","scopus_import":1,"day":"28","intvolume":" 224","title":"Genetic and pharmacological reversibility of phenotypes in mouse models of autism spectrum disorder","status":"public","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"634","oa_version":"None","alternative_title":["ADVSANAT"],"type":"book_chapter","abstract":[{"text":"As autism spectrum disorder (ASD) is largely regarded as a neurodevelopmental condition, long-time consensus was that its hallmark features are irreversible. However, several studies from recent years using defined mouse models of ASD have provided clear evidence that in mice neurobiological and behavioural alterations can be ameliorated or even reversed by genetic restoration or pharmacological treatment either before or after symptom onset. Here, we review findings on genetic and pharmacological reversibility of phenotypes in mouse models of ASD. Our review should give a comprehensive overview on both aspects and encourage future studies to better understand the underlying molecular mechanisms that might be translatable from animals to humans.","lang":"eng"}],"project":[{"name":"Transmembrane Transporters in Health and Disease","call_identifier":"FWF","_id":"25473368-B435-11E9-9278-68D0E5697425","grant_number":"F03523"}],"quality_controlled":"1","language":[{"iso":"eng"}],"doi":"10.1007/978-3-319-52498-6_10","publication_identifier":{"eisbn":["978-3-319-52498-6"]},"month":"05","department":[{"_id":"GaNo"}],"publisher":"Springer","editor":[{"last_name":"Schmeisser","first_name":"Michael","full_name":"Schmeisser, Michael"},{"full_name":"Boekers, Tobias","first_name":"Tobias","last_name":"Boekers"}],"publication_status":"published","year":"2017","volume":224,"date_updated":"2021-01-12T08:07:08Z","date_created":"2018-12-11T11:47:37Z","author":[{"full_name":"Schroeder, Jan","first_name":"Jan","last_name":"Schroeder"},{"full_name":"Deliu, Elena","last_name":"Deliu","first_name":"Elena","orcid":"0000-0002-7370-5293","id":"37A40D7E-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Novarino, Gaia","last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Schmeisser, Michael","first_name":"Michael","last_name":"Schmeisser"}],"publist_id":"7156"},{"quality_controlled":"1","publication":"Science Translational Medicine","citation":{"chicago":"Novarino, Gaia. “Modeling Alzheimer’s Disease in Mice with Human Neurons.” Science Translational Medicine. American Association for the Advancement of Science, 2017. https://doi.org/10.1126/scitranslmed.aam9867.","mla":"Novarino, Gaia. “Modeling Alzheimer’s Disease in Mice with Human Neurons.” Science Translational Medicine, vol. 9, no. 381, eaam9867, American Association for the Advancement of Science, 2017, doi:10.1126/scitranslmed.aam9867.","short":"G. Novarino, Science Translational Medicine 9 (2017).","ista":"Novarino G. 2017. Modeling Alzheimer’s disease in mice with human neurons. Science Translational Medicine. 9(381), eaam9867.","apa":"Novarino, G. (2017). Modeling Alzheimer’s disease in mice with human neurons. Science Translational Medicine. American Association for the Advancement of Science. https://doi.org/10.1126/scitranslmed.aam9867","ieee":"G. Novarino, “Modeling Alzheimer’s disease in mice with human neurons,” Science Translational Medicine, vol. 9, no. 381. American Association for the Advancement of Science, 2017.","ama":"Novarino G. Modeling Alzheimer’s disease in mice with human neurons. Science Translational Medicine. 2017;9(381). doi:10.1126/scitranslmed.aam9867"},"language":[{"iso":"eng"}],"doi":"10.1126/scitranslmed.aam9867","date_published":"2017-03-15T00:00:00Z","scopus_import":1,"month":"03","day":"15","publication_identifier":{"issn":["19466234"]},"publication_status":"published","status":"public","title":"Modeling Alzheimer's disease in mice with human neurons","intvolume":" 9","publisher":"American Association for the Advancement of Science","department":[{"_id":"GaNo"}],"_id":"656","year":"2017","user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","date_created":"2018-12-11T11:47:45Z","date_updated":"2021-01-12T08:07:59Z","volume":9,"oa_version":"None","author":[{"first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"}],"article_number":"eaam9867","type":"journal_article","abstract":[{"text":"Human neurons transplanted into a mouse model for Alzheimer’s disease show human-specific vulnerability to β-amyloid plaques and may help to identify new therapeutic targets.","lang":"eng"}],"issue":"381","publist_id":"7079"},{"publication":"Science Translational Medicine","citation":{"ama":"Novarino G. The antisocial side of antibiotics. Science Translational Medicine. 2017;9(387). doi:10.1126/scitranslmed.aan2786","ieee":"G. Novarino, “The antisocial side of antibiotics,” Science Translational Medicine, vol. 9, no. 387. American Association for the Advancement of Science, 2017.","apa":"Novarino, G. (2017). The antisocial side of antibiotics. Science Translational Medicine. American Association for the Advancement of Science. https://doi.org/10.1126/scitranslmed.aan2786","ista":"Novarino G. 2017. The antisocial side of antibiotics. Science Translational Medicine. 9(387), 2786.","short":"G. Novarino, Science Translational Medicine 9 (2017).","mla":"Novarino, Gaia. “The Antisocial Side of Antibiotics.” Science Translational Medicine, vol. 9, no. 387, 2786, American Association for the Advancement of Science, 2017, doi:10.1126/scitranslmed.aan2786.","chicago":"Novarino, Gaia. “The Antisocial Side of Antibiotics.” Science Translational Medicine. American Association for the Advancement of Science, 2017. https://doi.org/10.1126/scitranslmed.aan2786."},"quality_controlled":"1","date_published":"2017-04-26T00:00:00Z","doi":"10.1126/scitranslmed.aan2786","language":[{"iso":"eng"}],"scopus_import":1,"month":"04","day":"26","publication_identifier":{"issn":["19466234"]},"_id":"667","user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","year":"2017","title":"The antisocial side of antibiotics","publication_status":"published","status":"public","department":[{"_id":"GaNo"}],"intvolume":" 9","publisher":"American Association for the Advancement of Science","author":[{"full_name":"Novarino, Gaia","last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"}],"date_updated":"2021-01-12T08:08:30Z","date_created":"2018-12-11T11:47:48Z","volume":9,"oa_version":"None","article_number":"2786","type":"journal_article","abstract":[{"lang":"eng","text":"Perinatal exposure to penicillin may result in longlasting gut and behavioral changes."}],"issue":"387","publist_id":"7060"},{"type":"journal_article","article_number":"eaan8196","issue":"393","publist_id":"7019","abstract":[{"lang":"eng","text":"Rett syndrome modeling in monkey mirrors the human disorder."}],"user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","_id":"689","year":"2017","publisher":"American Association for the Advancement of Science","intvolume":" 9","department":[{"_id":"GaNo"}],"publication_status":"published","status":"public","title":"Rett syndrome modeling goes simian","author":[{"orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia","full_name":"Novarino, Gaia"}],"oa_version":"None","volume":9,"date_created":"2018-12-11T11:47:56Z","date_updated":"2021-01-12T08:09:29Z","scopus_import":1,"publication_identifier":{"issn":["19466234"]},"month":"06","day":"07","citation":{"chicago":"Novarino, Gaia. “Rett Syndrome Modeling Goes Simian.” Science Translational Medicine. American Association for the Advancement of Science, 2017. https://doi.org/10.1126/scitranslmed.aan8196.","mla":"Novarino, Gaia. “Rett Syndrome Modeling Goes Simian.” Science Translational Medicine, vol. 9, no. 393, eaan8196, American Association for the Advancement of Science, 2017, doi:10.1126/scitranslmed.aan8196.","short":"G. Novarino, Science Translational Medicine 9 (2017).","ista":"Novarino G. 2017. Rett syndrome modeling goes simian. Science Translational Medicine. 9(393), eaan8196.","apa":"Novarino, G. (2017). Rett syndrome modeling goes simian. Science Translational Medicine. American Association for the Advancement of Science. https://doi.org/10.1126/scitranslmed.aan8196","ieee":"G. Novarino, “Rett syndrome modeling goes simian,” Science Translational Medicine, vol. 9, no. 393. American Association for the Advancement of Science, 2017.","ama":"Novarino G. Rett syndrome modeling goes simian. Science Translational Medicine. 2017;9(393). doi:10.1126/scitranslmed.aan8196"},"publication":"Science Translational Medicine","quality_controlled":"1","date_published":"2017-06-07T00:00:00Z","doi":"10.1126/scitranslmed.aan8196","language":[{"iso":"eng"}]},{"day":"19","month":"07","publication_identifier":{"issn":["19466234"]},"scopus_import":1,"language":[{"iso":"eng"}],"doi":"10.1126/scitranslmed.aao0972","date_published":"2017-07-19T00:00:00Z","quality_controlled":"1","page":"eaao0972","publication":"Science Translational Medicine","citation":{"chicago":"Novarino, Gaia. “The Riddle of CHD8 Haploinsufficiency in Autism Spectrum Disorder.” Science Translational Medicine. American Association for the Advancement of Science, 2017. https://doi.org/10.1126/scitranslmed.aao0972.","mla":"Novarino, Gaia. “The Riddle of CHD8 Haploinsufficiency in Autism Spectrum Disorder.” Science Translational Medicine, vol. 9, no. 399, American Association for the Advancement of Science, 2017, p. eaao0972, doi:10.1126/scitranslmed.aao0972.","short":"G. Novarino, Science Translational Medicine 9 (2017) eaao0972.","ista":"Novarino G. 2017. The riddle of CHD8 haploinsufficiency in autism spectrum disorder. Science Translational Medicine. 9(399), eaao0972.","apa":"Novarino, G. (2017). The riddle of CHD8 haploinsufficiency in autism spectrum disorder. Science Translational Medicine. American Association for the Advancement of Science. https://doi.org/10.1126/scitranslmed.aao0972","ieee":"G. Novarino, “The riddle of CHD8 haploinsufficiency in autism spectrum disorder,” Science Translational Medicine, vol. 9, no. 399. American Association for the Advancement of Science, p. eaao0972, 2017.","ama":"Novarino G. The riddle of CHD8 haploinsufficiency in autism spectrum disorder. Science Translational Medicine. 2017;9(399):eaao0972. doi:10.1126/scitranslmed.aao0972"},"abstract":[{"text":"Leading autism-associated mutation in mouse partially mimics human disorder.\r\n\r\n","lang":"eng"}],"publist_id":"6993","issue":"399","type":"journal_article","date_created":"2018-12-11T11:48:01Z","date_updated":"2021-01-12T08:11:31Z","volume":9,"oa_version":"None","author":[{"full_name":"Novarino, Gaia","first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178"}],"title":"The riddle of CHD8 haploinsufficiency in autism spectrum disorder","publication_status":"published","status":"public","intvolume":" 9","department":[{"_id":"GaNo"}],"publisher":"American Association for the Advancement of Science","user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","_id":"702","year":"2017"},{"language":[{"iso":"eng"}],"doi":"10.7554/eLife.25125","quality_controlled":"1","project":[{"call_identifier":"FWF","name":"Revealing the mechanisms underlying drug interactions","grant_number":"P27201-B22","_id":"25E9AF9E-B435-11E9-9278-68D0E5697425"}],"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"month":"08","publication_identifier":{"issn":["2050084X"]},"date_updated":"2021-01-12T08:11:57Z","date_created":"2018-12-11T11:48:05Z","volume":6,"author":[{"full_name":"Andergassen, Daniel","first_name":"Daniel","last_name":"Andergassen"},{"id":"4C66542E-F248-11E8-B48F-1D18A9856A87","last_name":"Dotter","first_name":"Christoph","full_name":"Dotter, Christoph"},{"full_name":"Wenzel, Dyniel","last_name":"Wenzel","first_name":"Dyniel"},{"last_name":"Sigl","first_name":"Verena","full_name":"Sigl, Verena"},{"full_name":"Bammer, Philipp","first_name":"Philipp","last_name":"Bammer"},{"full_name":"Muckenhuber, Markus","first_name":"Markus","last_name":"Muckenhuber"},{"full_name":"Mayer, Daniela","last_name":"Mayer","first_name":"Daniela"},{"first_name":"Tomasz","last_name":"Kulinski","full_name":"Kulinski, Tomasz"},{"last_name":"Theussl","first_name":"Hans","full_name":"Theussl, Hans"},{"full_name":"Penninger, Josef","first_name":"Josef","last_name":"Penninger"},{"last_name":"Bock","first_name":"Christoph","full_name":"Bock, Christoph"},{"first_name":"Denise","last_name":"Barlow","full_name":"Barlow, Denise"},{"id":"48EA0138-F248-11E8-B48F-1D18A9856A87","last_name":"Pauler","first_name":"Florian","full_name":"Pauler, Florian"},{"full_name":"Hudson, Quanah","last_name":"Hudson","first_name":"Quanah"}],"publication_status":"published","department":[{"_id":"GaNo"},{"_id":"SiHi"}],"publisher":"eLife Sciences Publications","year":"2017","file_date_updated":"2020-07-14T12:47:50Z","publist_id":"6971","article_number":"e25125","date_published":"2017-08-14T00:00:00Z","publication":"eLife","citation":{"ieee":"D. Andergassen et al., “Mapping the mouse Allelome reveals tissue specific regulation of allelic expression,” eLife, vol. 6. eLife Sciences Publications, 2017.","apa":"Andergassen, D., Dotter, C., Wenzel, D., Sigl, V., Bammer, P., Muckenhuber, M., … Hudson, Q. (2017). Mapping the mouse Allelome reveals tissue specific regulation of allelic expression. ELife. eLife Sciences Publications. https://doi.org/10.7554/eLife.25125","ista":"Andergassen D, Dotter C, Wenzel D, Sigl V, Bammer P, Muckenhuber M, Mayer D, Kulinski T, Theussl H, Penninger J, Bock C, Barlow D, Pauler F, Hudson Q. 2017. Mapping the mouse Allelome reveals tissue specific regulation of allelic expression. eLife. 6, e25125.","ama":"Andergassen D, Dotter C, Wenzel D, et al. Mapping the mouse Allelome reveals tissue specific regulation of allelic expression. eLife. 2017;6. doi:10.7554/eLife.25125","chicago":"Andergassen, Daniel, Christoph Dotter, Dyniel Wenzel, Verena Sigl, Philipp Bammer, Markus Muckenhuber, Daniela Mayer, et al. “Mapping the Mouse Allelome Reveals Tissue Specific Regulation of Allelic Expression.” ELife. eLife Sciences Publications, 2017. https://doi.org/10.7554/eLife.25125.","short":"D. Andergassen, C. Dotter, D. Wenzel, V. Sigl, P. Bammer, M. Muckenhuber, D. Mayer, T. Kulinski, H. Theussl, J. Penninger, C. Bock, D. Barlow, F. Pauler, Q. Hudson, ELife 6 (2017).","mla":"Andergassen, Daniel, et al. “Mapping the Mouse Allelome Reveals Tissue Specific Regulation of Allelic Expression.” ELife, vol. 6, e25125, eLife Sciences Publications, 2017, doi:10.7554/eLife.25125."},"day":"14","has_accepted_license":"1","scopus_import":1,"oa_version":"Published Version","file":[{"relation":"main_file","file_id":"5020","checksum":"1ace3462e64a971b9ead896091829549","date_created":"2018-12-12T10:13:36Z","date_updated":"2020-07-14T12:47:50Z","access_level":"open_access","file_name":"IST-2017-885-v1+1_elife-25125-figures-v2.pdf","content_type":"application/pdf","file_size":6399510,"creator":"system"},{"relation":"main_file","file_id":"5021","checksum":"6241dc31eeb87b03facadec3a53a6827","date_updated":"2020-07-14T12:47:50Z","date_created":"2018-12-12T10:13:36Z","access_level":"open_access","file_name":"IST-2017-885-v1+2_elife-25125-v2.pdf","file_size":4264398,"content_type":"application/pdf","creator":"system"}],"pubrep_id":"885","title":"Mapping the mouse Allelome reveals tissue specific regulation of allelic expression","status":"public","ddc":["576"],"intvolume":" 6","_id":"713","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","abstract":[{"lang":"eng","text":"To determine the dynamics of allelic-specific expression during mouse development, we analyzed RNA-seq data from 23 F1 tissues from different developmental stages, including 19 female tissues allowing X chromosome inactivation (XCI) escapers to also be detected. We demonstrate that allelic expression arising from genetic or epigenetic differences is highly tissue-specific. We find that tissue-specific strain-biased gene expression may be regulated by tissue-specific enhancers or by post-transcriptional differences in stability between the alleles. We also find that escape from X-inactivation is tissue-specific, with leg muscle showing an unexpectedly high rate of XCI escapers. By surveying a range of tissues during development, and performing extensive validation, we are able to provide a high confidence list of mouse imprinted genes including 18 novel genes. This shows that cluster size varies dynamically during development and can be substantially larger than previously thought, with the Igf2r cluster extending over 10 Mb in placenta."}],"type":"journal_article"},{"day":"01","article_processing_charge":"No","scopus_import":1,"date_published":"2017-09-01T00:00:00Z","article_type":"original","page":"7 - 14","publication":"Drug and Alcohol Dependence","citation":{"apa":"Brailoiu, G., Deliu, E., Barr, J., Console Bram, L., Ciuciu, A., Abood, M., … Brǎiloiu, E. (2017). HIV Tat excites D1 receptor-like expressing neurons from rat nucleus accumbens. Drug and Alcohol Dependence. Elsevier. https://doi.org/10.1016/j.drugalcdep.2017.04.015","ieee":"G. Brailoiu et al., “HIV Tat excites D1 receptor-like expressing neurons from rat nucleus accumbens,” Drug and Alcohol Dependence, vol. 178. Elsevier, pp. 7–14, 2017.","ista":"Brailoiu G, Deliu E, Barr J, Console Bram L, Ciuciu A, Abood M, Unterwald E, Brǎiloiu E. 2017. HIV Tat excites D1 receptor-like expressing neurons from rat nucleus accumbens. Drug and Alcohol Dependence. 178, 7–14.","ama":"Brailoiu G, Deliu E, Barr J, et al. HIV Tat excites D1 receptor-like expressing neurons from rat nucleus accumbens. Drug and Alcohol Dependence. 2017;178:7-14. doi:10.1016/j.drugalcdep.2017.04.015","chicago":"Brailoiu, Gabriela, Elena Deliu, Jeffrey Barr, Linda Console Bram, Alexandra Ciuciu, Mary Abood, Ellen Unterwald, and Eugen Brǎiloiu. “HIV Tat Excites D1 Receptor-like Expressing Neurons from Rat Nucleus Accumbens.” Drug and Alcohol Dependence. Elsevier, 2017. https://doi.org/10.1016/j.drugalcdep.2017.04.015.","short":"G. Brailoiu, E. Deliu, J. Barr, L. Console Bram, A. Ciuciu, M. Abood, E. Unterwald, E. Brǎiloiu, Drug and Alcohol Dependence 178 (2017) 7–14.","mla":"Brailoiu, Gabriela, et al. “HIV Tat Excites D1 Receptor-like Expressing Neurons from Rat Nucleus Accumbens.” Drug and Alcohol Dependence, vol. 178, Elsevier, 2017, pp. 7–14, doi:10.1016/j.drugalcdep.2017.04.015."},"abstract":[{"text":"Background HIV-1 infection and drug abuse are frequently co-morbid and their association greatly increases the severity of HIV-1-induced neuropathology. While nucleus accumbens (NAcc) function is severely perturbed by drugs of abuse, little is known about how HIV-1 infection affects NAcc. Methods We used calcium and voltage imaging to investigate the effect of HIV-1 trans-activator of transcription (Tat) on rat NAcc. Based on previous neuronal studies, we hypothesized that Tat modulates intracellular Ca2+ homeostasis of NAcc neurons. Results We provide evidence that Tat triggers a Ca2+ signaling cascade in NAcc medium spiny neurons (MSN) expressing D1-like dopamine receptors leading to neuronal depolarization. Firstly, Tat induced inositol 1,4,5-trisphsophate (IP3) receptor-mediated Ca2+ release from endoplasmic reticulum, followed by Ca2+ and Na+ influx via transient receptor potential canonical channels. The influx of cations depolarizes the membrane promoting additional Ca2+ entry through voltage-gated P/Q-type Ca2+ channels and opening of tetrodotoxin-sensitive Na+ channels. By activating this mechanism, Tat elicits a feed-forward depolarization increasing the excitability of D1-phosphatidylinositol-linked NAcc MSN. We previously found that cocaine targets NAcc neurons directly (independent of the inhibition of dopamine transporter) only when IP3-generating mechanisms are concomitantly initiated. When tested here, cocaine produced a dose-dependent potentiation of the effect of Tat on cytosolic Ca2+. Conclusion We describe for the first time a HIV-1 Tat-triggered Ca2+ signaling in MSN of NAcc involving TRPC and depolarization and a potentiation of the effect of Tat by cocaine, which may be relevant for the reward axis in cocaine-abusing HIV-1-positive patients.","lang":"eng"}],"type":"journal_article","oa_version":"Submitted Version","status":"public","title":"HIV Tat excites D1 receptor-like expressing neurons from rat nucleus accumbens","intvolume":" 178","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"714","month":"09","publication_identifier":{"issn":["03768716"]},"language":[{"iso":"eng"}],"doi":"10.1016/j.drugalcdep.2017.04.015","quality_controlled":"1","oa":1,"main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797705"}],"external_id":{"pmid":["28623807"]},"publist_id":"6967","date_updated":"2021-01-12T08:12:00Z","date_created":"2018-12-11T11:48:05Z","volume":178,"author":[{"full_name":"Brailoiu, Gabriela","first_name":"Gabriela","last_name":"Brailoiu"},{"full_name":"Deliu, Elena","orcid":"0000-0002-7370-5293","id":"37A40D7E-F248-11E8-B48F-1D18A9856A87","last_name":"Deliu","first_name":"Elena"},{"full_name":"Barr, Jeffrey","last_name":"Barr","first_name":"Jeffrey"},{"first_name":"Linda","last_name":"Console Bram","full_name":"Console Bram, Linda"},{"first_name":"Alexandra","last_name":"Ciuciu","full_name":"Ciuciu, Alexandra"},{"full_name":"Abood, Mary","last_name":"Abood","first_name":"Mary"},{"first_name":"Ellen","last_name":"Unterwald","full_name":"Unterwald, Ellen"},{"full_name":"Brǎiloiu, Eugen","last_name":"Brǎiloiu","first_name":"Eugen"}],"publication_status":"published","department":[{"_id":"GaNo"}],"publisher":"Elsevier","year":"2017","acknowledgement":"This work was supported by the National Institutes of Health grants DA035926 (to MEA), and P30DA013429 (to EMU).","pmid":1},{"type":"journal_article","article_number":"aao4218","publist_id":"6968","issue":"405","abstract":[{"text":"D-cycloserine ameliorates breathing abnormalities and survival rate in a mouse model of Rett syndrome.","lang":"eng"}],"intvolume":" 9","publisher":"American Association for the Advancement of Science","department":[{"_id":"GaNo"}],"publication_status":"published","status":"public","title":"More excitation for Rett syndrome","_id":"715","year":"2017","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","volume":9,"oa_version":"None","date_created":"2018-12-11T11:48:06Z","date_updated":"2021-01-12T08:12:04Z","author":[{"last_name":"Novarino","first_name":"Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","full_name":"Novarino, Gaia"}],"scopus_import":1,"publication_identifier":{"issn":["19466234"]},"month":"08","day":"30","quality_controlled":"1","citation":{"chicago":"Novarino, Gaia. “More Excitation for Rett Syndrome.” Science Translational Medicine. American Association for the Advancement of Science, 2017. https://doi.org/10.1126/scitranslmed.aao4218.","mla":"Novarino, Gaia. “More Excitation for Rett Syndrome.” Science Translational Medicine, vol. 9, no. 405, aao4218, American Association for the Advancement of Science, 2017, doi:10.1126/scitranslmed.aao4218.","short":"G. Novarino, Science Translational Medicine 9 (2017).","ista":"Novarino G. 2017. More excitation for Rett syndrome. Science Translational Medicine. 9(405), aao4218.","apa":"Novarino, G. (2017). More excitation for Rett syndrome. Science Translational Medicine. American Association for the Advancement of Science. https://doi.org/10.1126/scitranslmed.aao4218","ieee":"G. Novarino, “More excitation for Rett syndrome,” Science Translational Medicine, vol. 9, no. 405. American Association for the Advancement of Science, 2017.","ama":"Novarino G. More excitation for Rett syndrome. Science Translational Medicine. 2017;9(405). doi:10.1126/scitranslmed.aao4218"},"publication":"Science Translational Medicine","language":[{"iso":"eng"}],"date_published":"2017-08-30T00:00:00Z","doi":"10.1126/scitranslmed.aao4218"},{"year":"2017","_id":"731","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","status":"public","publication_status":"published","title":"The science of love in ASD and ADHD","department":[{"_id":"GaNo"}],"intvolume":" 9","publisher":"American Association for the Advancement of Science","author":[{"first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"}],"date_created":"2018-12-11T11:48:12Z","date_updated":"2021-01-12T08:12:57Z","volume":9,"oa_version":"None","article_number":"eaap8168","type":"journal_article","abstract":[{"lang":"eng","text":"Genetic variations in the oxytocin receptor gene affect patients with ASD and ADHD differently."}],"issue":"411","publist_id":"6938","publication":"Science Translational Medicine","citation":{"chicago":"Novarino, Gaia. “The Science of Love in ASD and ADHD.” Science Translational Medicine. American Association for the Advancement of Science, 2017. https://doi.org/10.1126/scitranslmed.aap8168.","mla":"Novarino, Gaia. “The Science of Love in ASD and ADHD.” Science Translational Medicine, vol. 9, no. 411, eaap8168, American Association for the Advancement of Science, 2017, doi:10.1126/scitranslmed.aap8168.","short":"G. Novarino, Science Translational Medicine 9 (2017).","ista":"Novarino G. 2017. The science of love in ASD and ADHD. Science Translational Medicine. 9(411), eaap8168.","apa":"Novarino, G. (2017). The science of love in ASD and ADHD. Science Translational Medicine. American Association for the Advancement of Science. https://doi.org/10.1126/scitranslmed.aap8168","ieee":"G. Novarino, “The science of love in ASD and ADHD,” Science Translational Medicine, vol. 9, no. 411. American Association for the Advancement of Science, 2017.","ama":"Novarino G. The science of love in ASD and ADHD. Science Translational Medicine. 2017;9(411). doi:10.1126/scitranslmed.aap8168"},"quality_controlled":"1","date_published":"2017-10-11T00:00:00Z","doi":"10.1126/scitranslmed.aap8168","language":[{"iso":"eng"}],"scopus_import":1,"day":"11","month":"10","publication_identifier":{"issn":["19466234"]}},{"scopus_import":"1","day":"01","article_processing_charge":"No","has_accepted_license":"1","article_type":"review","page":"45 - 57","publication":"European Journal of Neuroscience","citation":{"ama":"Sauerzopf U, Sacco R, Novarino G, et al. Are reprogrammed cells a useful tool for studying dopamine dysfunction in psychotic disorders? A review of the current evidence. European Journal of Neuroscience. 2017;45(1):45-57. doi:10.1111/ejn.13418","ista":"Sauerzopf U, Sacco R, Novarino G, Niello M, Weidenauer A, Praschak Rieder N, Sitte H, Willeit M. 2017. Are reprogrammed cells a useful tool for studying dopamine dysfunction in psychotic disorders? A review of the current evidence. European Journal of Neuroscience. 45(1), 45–57.","apa":"Sauerzopf, U., Sacco, R., Novarino, G., Niello, M., Weidenauer, A., Praschak Rieder, N., … Willeit, M. (2017). Are reprogrammed cells a useful tool for studying dopamine dysfunction in psychotic disorders? A review of the current evidence. European Journal of Neuroscience. Wiley-Blackwell. https://doi.org/10.1111/ejn.13418","ieee":"U. Sauerzopf et al., “Are reprogrammed cells a useful tool for studying dopamine dysfunction in psychotic disorders? A review of the current evidence,” European Journal of Neuroscience, vol. 45, no. 1. Wiley-Blackwell, pp. 45–57, 2017.","mla":"Sauerzopf, Ulrich, et al. “Are Reprogrammed Cells a Useful Tool for Studying Dopamine Dysfunction in Psychotic Disorders? A Review of the Current Evidence.” European Journal of Neuroscience, vol. 45, no. 1, Wiley-Blackwell, 2017, pp. 45–57, doi:10.1111/ejn.13418.","short":"U. Sauerzopf, R. Sacco, G. Novarino, M. Niello, A. Weidenauer, N. Praschak Rieder, H. Sitte, M. Willeit, European Journal of Neuroscience 45 (2017) 45–57.","chicago":"Sauerzopf, Ulrich, Roberto Sacco, Gaia Novarino, Marco Niello, Ana Weidenauer, Nicole Praschak Rieder, Harald Sitte, and Matthaeus Willeit. “Are Reprogrammed Cells a Useful Tool for Studying Dopamine Dysfunction in Psychotic Disorders? A Review of the Current Evidence.” European Journal of Neuroscience. Wiley-Blackwell, 2017. https://doi.org/10.1111/ejn.13418."},"date_published":"2017-01-01T00:00:00Z","type":"journal_article","abstract":[{"text":"Since 2006, reprogrammed cells have increasingly been used as a biomedical research technique in addition to neuro-psychiatric methods. These rapidly evolving techniques allow for the generation of neuronal sub-populations, and have sparked interest not only in monogenetic neuro-psychiatric diseases, but also in poly-genetic and poly-aetiological disorders such as schizophrenia (SCZ) and bipolar disorder (BPD). This review provides a summary of 19 publications on reprogrammed adult somatic cells derived from patients with SCZ, and five publications using this technique in patients with BPD. As both disorders are complex and heterogeneous, there is a plurality of hypotheses to be tested in vitro. In SCZ, data on alterations of dopaminergic transmission in vitro are sparse, despite the great explanatory power of the so-called DA hypothesis of SCZ. Some findings correspond to perturbations of cell energy metabolism, and observations in reprogrammed cells suggest neuro-developmental alterations. Some studies also report on the efficacy of medicinal compounds to revert alterations observed in cellular models. However, due to the paucity of replication studies, no comprehensive conclusions can be drawn from studies using reprogrammed cells at the present time. In the future, findings from cell culture methods need to be integrated with clinical, epidemiological, pharmacological and imaging data in order to generate a more comprehensive picture of SCZ and BPD.","lang":"eng"}],"issue":"1","title":"Are reprogrammed cells a useful tool for studying dopamine dysfunction in psychotic disorders? A review of the current evidence","status":"public","ddc":["616"],"intvolume":" 45","_id":"1228","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","oa_version":"Published Version","file":[{"relation":"main_file","file_id":"4838","checksum":"c572cf02be8fbb7020cfcfb892182e4c","date_updated":"2020-07-14T12:44:39Z","date_created":"2018-12-12T10:10:48Z","access_level":"open_access","file_name":"IST-2017-738-v1+1_Sauerzopf_et_al-2017-European_Journal_of_Neuroscience.pdf","file_size":169145,"content_type":"application/pdf","creator":"system"}],"pubrep_id":"738","month":"01","quality_controlled":"1","isi":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"external_id":{"pmid":["27690184"],"isi":["000392487100005"]},"oa":1,"language":[{"iso":"eng"}],"doi":"10.1111/ejn.13418","file_date_updated":"2020-07-14T12:44:39Z","publist_id":"6106","publication_status":"published","publisher":"Wiley-Blackwell","department":[{"_id":"GaNo"}],"acknowledgement":"This work was supported by grants of the Austrian Science Fund (FWF) P23585B09 to M.W. and F3506 to H.H.S. and the “Wiener Wissenschafts-, Forschungs- und Technologiefonds” (Vienna Science and Technology Fund; WWTF) CS15-033 to M.W.","year":"2017","pmid":1,"date_created":"2018-12-11T11:50:50Z","date_updated":"2023-09-20T11:16:01Z","volume":45,"author":[{"first_name":"Ulrich","last_name":"Sauerzopf","full_name":"Sauerzopf, Ulrich"},{"full_name":"Sacco, Roberto","first_name":"Roberto","last_name":"Sacco","id":"42C9F57E-F248-11E8-B48F-1D18A9856A87"},{"orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia","full_name":"Novarino, Gaia"},{"full_name":"Niello, Marco","last_name":"Niello","first_name":"Marco"},{"full_name":"Weidenauer, Ana","last_name":"Weidenauer","first_name":"Ana"},{"full_name":"Praschak Rieder, Nicole","last_name":"Praschak Rieder","first_name":"Nicole"},{"full_name":"Sitte, Harald","last_name":"Sitte","first_name":"Harald"},{"first_name":"Matthaeus","last_name":"Willeit","full_name":"Willeit, Matthaeus"}]},{"doi":"10.1016/j.neuroscience.2017.09.034","language":[{"iso":"eng"}],"oa":1,"external_id":{"isi":["000415966200003"],"pmid":["28951324"]},"main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5798458"}],"quality_controlled":"1","isi":1,"publication_identifier":{"issn":["03064522"]},"month":"12","author":[{"full_name":"Brǎiloiu, Eugen","first_name":"Eugen","last_name":"Brǎiloiu"},{"last_name":"Mcguire","first_name":"Matthew","full_name":"Mcguire, Matthew"},{"full_name":"Shuler, Shadaria","first_name":"Shadaria","last_name":"Shuler"},{"id":"37A40D7E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7370-5293","first_name":"Elena","last_name":"Deliu","full_name":"Deliu, Elena"},{"first_name":"Jeffrey","last_name":"Barr","full_name":"Barr, Jeffrey"},{"full_name":"Abood, Mary","first_name":"Mary","last_name":"Abood"},{"full_name":"Brailoiu, Gabriela","last_name":"Brailoiu","first_name":"Gabriela"}],"volume":365,"date_created":"2018-12-11T11:48:17Z","date_updated":"2023-09-27T12:26:59Z","pmid":1,"year":"2017","department":[{"_id":"GaNo"}],"publisher":"Elsevier","publication_status":"published","publist_id":"6911","date_published":"2017-12-04T00:00:00Z","citation":{"chicago":"Brǎiloiu, Eugen, Matthew Mcguire, Shadaria Shuler, Elena Deliu, Jeffrey Barr, Mary Abood, and Gabriela Brailoiu. “Modulation of Cardiac Vagal Tone by Bradykinin Acting on Nucleus Ambiguus.” Neuroscience. Elsevier, 2017. https://doi.org/10.1016/j.neuroscience.2017.09.034.","mla":"Brǎiloiu, Eugen, et al. “Modulation of Cardiac Vagal Tone by Bradykinin Acting on Nucleus Ambiguus.” Neuroscience, vol. 365, Elsevier, 2017, pp. 23–32, doi:10.1016/j.neuroscience.2017.09.034.","short":"E. Brǎiloiu, M. Mcguire, S. Shuler, E. Deliu, J. Barr, M. Abood, G. Brailoiu, Neuroscience 365 (2017) 23–32.","ista":"Brǎiloiu E, Mcguire M, Shuler S, Deliu E, Barr J, Abood M, Brailoiu G. 2017. Modulation of cardiac vagal tone by bradykinin acting on nucleus ambiguus. Neuroscience. 365, 23–32.","ieee":"E. Brǎiloiu et al., “Modulation of cardiac vagal tone by bradykinin acting on nucleus ambiguus,” Neuroscience, vol. 365. Elsevier, pp. 23–32, 2017.","apa":"Brǎiloiu, E., Mcguire, M., Shuler, S., Deliu, E., Barr, J., Abood, M., & Brailoiu, G. (2017). Modulation of cardiac vagal tone by bradykinin acting on nucleus ambiguus. Neuroscience. Elsevier. https://doi.org/10.1016/j.neuroscience.2017.09.034","ama":"Brǎiloiu E, Mcguire M, Shuler S, et al. Modulation of cardiac vagal tone by bradykinin acting on nucleus ambiguus. Neuroscience. 2017;365:23-32. doi:10.1016/j.neuroscience.2017.09.034"},"publication":"Neuroscience","page":"23 - 32","article_type":"original","article_processing_charge":"No","day":"04","scopus_import":"1","oa_version":"Submitted Version","_id":"747","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","intvolume":" 365","status":"public","title":"Modulation of cardiac vagal tone by bradykinin acting on nucleus ambiguus","abstract":[{"text":"Bradykinin (BK), a component of the kallikrein-kininogen-kinin system exerts multiple effects via B1 and B2 receptor activation. In the cardiovascular system, bradykinin has cardioprotective and vasodilator properties. We investigated the effect of BK on cardiac-projecting neurons of nucleus ambiguus, a key site for the parasympathetic cardiac regulation. BK produced a dose-dependent increase in cytosolic Ca2+ concentration. Pretreatment with HOE140, a B2 receptor antagonist, but not with R715, a B1 receptor antagonist, abolished the response to BK. A selective B2 receptor agonist, but not a B1 receptor agonist, elicited an increase in cytosolic Ca2+ similarly to BK. Inhibition of N-type voltage-gated Ca2+ channels with ω-conotoxin GVIA had no effect on the Ca2+ signal produced by BK, while pretreatment with ω-conotoxin MVIIC, a blocker of P/Q-type of Ca2+ channels, significantly diminished the effect of BK. Pretreatment with xestospongin C and 2-aminoethoxydiphenyl borate, antagonists of inositol 1,4,5-trisphosphate receptors, abolished the response to BK. Inhibition of ryanodine receptors reduced the BK-induced Ca2+ increase, while disruption of lysosomal Ca2+ stores with bafilomycin A1 did not affect the response. BK produced a dose-dependent depolarization of nucleus ambiguus neurons, which was prevented by the B2 receptor antagonist. In vivo studies indicate that microinjection of BK into nucleus ambiguus elicited bradycardia in conscious rats via B2 receptors. In summary, in cardiac vagal neurons of nucleus ambiguus, BK activates B2 receptors promoting Ca2+ influx and Ca2+ release from endoplasmic reticulum, and membrane depolarization; these effects are translated in vivo by bradycardia.","lang":"eng"}],"type":"journal_article"},{"file_date_updated":"2020-07-14T12:44:41Z","publist_id":"6093","article_number":"14","date_updated":"2021-01-12T06:49:20Z","date_created":"2018-12-11T11:50:53Z","volume":17,"author":[{"first_name":"Aleksandra","last_name":"Kornienko","full_name":"Kornienko, Aleksandra"},{"first_name":"Christoph","last_name":"Dotter","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","full_name":"Dotter, Christoph"},{"first_name":"Philipp","last_name":"Guenzl","full_name":"Guenzl, Philipp"},{"full_name":"Gisslinger, Heinz","first_name":"Heinz","last_name":"Gisslinger"},{"full_name":"Gisslinger, Bettina","first_name":"Bettina","last_name":"Gisslinger"},{"last_name":"Cleary","first_name":"Ciara","full_name":"Cleary, Ciara"},{"full_name":"Kralovics, Robert","first_name":"Robert","last_name":"Kralovics"},{"full_name":"Pauler, Florian","id":"48EA0138-F248-11E8-B48F-1D18A9856A87","last_name":"Pauler","first_name":"Florian"},{"last_name":"Barlow","first_name":"Denise","full_name":"Barlow, Denise"}],"publication_status":"published","publisher":"BioMed Central","department":[{"_id":"GaNo"}],"acknowledgement":"This study was partly funded by the Austrian Science Fund (FWF F43-B09, FWF W1207-B09). PMG is a recipient of a DOC Fellowship of the Austrian Academy of Sciences.\r\nWe thank Ruth Klement, Tomasz Kulinski, Elisangela Valente, Elisabeth Salzer,\r\nand Roland Jäger for technical/bioinformatic assistance and advice, the CeMM\r\nIT department and José Manuel Molero for help and advice on software usage,\r\nthe Biomedical Sequencing Facility (http://biomedical-sequencing.at/) for\r\nsequencing and advice, Jacques Colinge, Daniel Andergassen, and Tomasz\r\nKulinski for discussions, Quanah Hudson and Jörg Menche for reading and\r\ncommenting on the manuscript.","year":"2016","month":"01","language":[{"iso":"eng"}],"doi":"10.1186/s13059-016-0873-8","quality_controlled":"1","oa":1,"tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"abstract":[{"text":"Background: Long non-coding RNAs (lncRNAs) are increasingly implicated as gene regulators and may ultimately be more numerous than protein-coding genes in the human genome. Despite large numbers of reported lncRNAs, reference annotations are likely incomplete due to their lower and tighter tissue-specific expression compared to mRNAs. An unexplored factor potentially confounding lncRNA identification is inter-individual expression variability. Here, we characterize lncRNA natural expression variability in human primary granulocytes. Results: We annotate granulocyte lncRNAs and mRNAs in RNA-seq data from 10 healthy individuals, identifying multiple lncRNAs absent from reference annotations, and use this to investigate three known features (higher tissue-specificity, lower expression, and reduced splicing efficiency) of lncRNAs relative to mRNAs. Expression variability was examined in seven individuals sampled three times at 1- or more than 1-month intervals. We show that lncRNAs display significantly more inter-individual expression variability compared to mRNAs. We confirm this finding in two independent human datasets by analyzing multiple tissues from the GTEx project and lymphoblastoid cell lines from the GEUVADIS project. Using the latter dataset we also show that including more human donors into the transcriptome annotation pipeline allows identification of an increasing number of lncRNAs, but minimally affects mRNA gene number. Conclusions: A comprehensive annotation of lncRNAs is known to require an approach that is sensitive to low and tight tissue-specific expression. Here we show that increased inter-individual expression variability is an additional general lncRNA feature to consider when creating a comprehensive annotation of human lncRNAs or proposing their use as prognostic or disease markers.","lang":"eng"}],"issue":"1","type":"journal_article","oa_version":"Published Version","file":[{"date_updated":"2020-07-14T12:44:41Z","date_created":"2018-12-12T10:10:05Z","checksum":"a268beee1a690801c83ec6729f9ebc5b","file_id":"4789","relation":"main_file","creator":"system","file_size":2914601,"content_type":"application/pdf","file_name":"IST-2016-709-v1+1_s13059-016-0873-8.pdf","access_level":"open_access"}],"pubrep_id":"709","title":"Long non-coding RNAs display higher natural expression variation than protein-coding genes in healthy humans","status":"public","ddc":["576"],"intvolume":" 17","user_id":"3E5EF7F0-F248-11E8-B48F-1D18A9856A87","_id":"1240","day":"29","has_accepted_license":"1","scopus_import":1,"date_published":"2016-01-29T00:00:00Z","publication":"Genome Biology","citation":{"ama":"Kornienko A, Dotter C, Guenzl P, et al. Long non-coding RNAs display higher natural expression variation than protein-coding genes in healthy humans. Genome Biology. 2016;17(1). doi:10.1186/s13059-016-0873-8","ista":"Kornienko A, Dotter C, Guenzl P, Gisslinger H, Gisslinger B, Cleary C, Kralovics R, Pauler F, Barlow D. 2016. Long non-coding RNAs display higher natural expression variation than protein-coding genes in healthy humans. Genome Biology. 17(1), 14.","apa":"Kornienko, A., Dotter, C., Guenzl, P., Gisslinger, H., Gisslinger, B., Cleary, C., … Barlow, D. (2016). Long non-coding RNAs display higher natural expression variation than protein-coding genes in healthy humans. Genome Biology. BioMed Central. https://doi.org/10.1186/s13059-016-0873-8","ieee":"A. Kornienko et al., “Long non-coding RNAs display higher natural expression variation than protein-coding genes in healthy humans,” Genome Biology, vol. 17, no. 1. BioMed Central, 2016.","mla":"Kornienko, Aleksandra, et al. “Long Non-Coding RNAs Display Higher Natural Expression Variation than Protein-Coding Genes in Healthy Humans.” Genome Biology, vol. 17, no. 1, 14, BioMed Central, 2016, doi:10.1186/s13059-016-0873-8.","short":"A. Kornienko, C. Dotter, P. Guenzl, H. Gisslinger, B. Gisslinger, C. Cleary, R. Kralovics, F. Pauler, D. Barlow, Genome Biology 17 (2016).","chicago":"Kornienko, Aleksandra, Christoph Dotter, Philipp Guenzl, Heinz Gisslinger, Bettina Gisslinger, Ciara Cleary, Robert Kralovics, Florian Pauler, and Denise Barlow. “Long Non-Coding RNAs Display Higher Natural Expression Variation than Protein-Coding Genes in Healthy Humans.” Genome Biology. BioMed Central, 2016. https://doi.org/10.1186/s13059-016-0873-8."}},{"date_published":"2016-12-01T00:00:00Z","publication":"Cell","citation":{"ista":"Tarlungeanu D-C, Deliu E, Dotter C, Kara M, Janiesch P, Scalise M, Galluccio M, Tesulov M, Morelli E, Sönmez F, Bilgüvar K, Ohgaki R, Kanai Y, Johansen A, Esharif S, Ben Omran T, Topcu M, Schlessinger A, Indiveri C, Duncan K, Caglayan A, Günel M, Gleeson J, Novarino G. 2016. Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder. Cell. 167(6), 1481–1494.","ieee":"D.-C. Tarlungeanu et al., “Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder,” Cell, vol. 167, no. 6. Cell Press, pp. 1481–1494, 2016.","apa":"Tarlungeanu, D.-C., Deliu, E., Dotter, C., Kara, M., Janiesch, P., Scalise, M., … Novarino, G. (2016). Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder. Cell. Cell Press. https://doi.org/10.1016/j.cell.2016.11.013","ama":"Tarlungeanu D-C, Deliu E, Dotter C, et al. Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder. Cell. 2016;167(6):1481-1494. doi:10.1016/j.cell.2016.11.013","chicago":"Tarlungeanu, Dora-Clara, Elena Deliu, Christoph Dotter, Majdi Kara, Philipp Janiesch, Mariafrancesca Scalise, Michele Galluccio, et al. “Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder.” Cell. Cell Press, 2016. https://doi.org/10.1016/j.cell.2016.11.013.","mla":"Tarlungeanu, Dora-Clara, et al. “Impaired Amino Acid Transport at the Blood Brain Barrier Is a Cause of Autism Spectrum Disorder.” Cell, vol. 167, no. 6, Cell Press, 2016, pp. 1481–94, doi:10.1016/j.cell.2016.11.013.","short":"D.-C. Tarlungeanu, E. Deliu, C. Dotter, M. Kara, P. Janiesch, M. Scalise, M. Galluccio, M. Tesulov, E. Morelli, F. Sönmez, K. Bilgüvar, R. Ohgaki, Y. Kanai, A. Johansen, S. Esharif, T. Ben Omran, M. Topcu, A. Schlessinger, C. Indiveri, K. Duncan, A. Caglayan, M. Günel, J. Gleeson, G. Novarino, Cell 167 (2016) 1481–1494."},"article_type":"original","page":"1481 - 1494","day":"01","has_accepted_license":"1","article_processing_charge":"No","scopus_import":"1","pubrep_id":"771","oa_version":"Submitted Version","file":[{"access_level":"open_access","file_name":"IST-2017-771-v1+1_Tarlungeanu_et_al._Final_edited.pdf","creator":"system","file_size":73907957,"content_type":"application/pdf","file_id":"5030","relation":"main_file","checksum":"7fe01ab12a6610d3db421e0136db2f77","date_created":"2018-12-12T10:13:44Z","date_updated":"2020-07-14T12:44:37Z"}],"_id":"1183","user_id":"8b945eb4-e2f2-11eb-945a-df72226e66a9","status":"public","ddc":["576","616"],"title":"Impaired amino acid transport at the blood brain barrier is a cause of autism spectrum disorder","intvolume":" 167","abstract":[{"text":"Autism spectrum disorders (ASD) are a group of genetic disorders often overlapping with other neurological conditions. We previously described abnormalities in the branched-chain amino acid (BCAA) catabolic pathway as a cause of ASD. Here, we show that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid transporter localized at the blood brain barrier (BBB), has an essential role in maintaining normal levels of brain BCAAs. In mice, deletion of Slc7a5 from the endothelial cells of the BBB leads to atypical brain amino acid profile, abnormal mRNA translation, and severe neurological abnormalities. Furthermore, we identified several patients with autistic traits and motor delay carrying deleterious homozygous mutations in the SLC7A5 gene. Finally, we demonstrate that BCAA intracerebroventricular administration ameliorates abnormal behaviors in adult mutant mice. Our data elucidate a neurological syndrome defined by SLC7A5 mutations and support an essential role for the BCAA in human brain function.","lang":"eng"}],"issue":"6","type":"journal_article","doi":"10.1016/j.cell.2016.11.013","language":[{"iso":"eng"}],"oa":1,"quality_controlled":"1","project":[{"grant_number":"F03523","_id":"25473368-B435-11E9-9278-68D0E5697425","name":"Transmembrane Transporters in Health and Disease","call_identifier":"FWF"}],"month":"12","author":[{"full_name":"Tarlungeanu, Dora-Clara","id":"2ABCE612-F248-11E8-B48F-1D18A9856A87","first_name":"Dora-Clara","last_name":"Tarlungeanu"},{"full_name":"Deliu, Elena","id":"37A40D7E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7370-5293","first_name":"Elena","last_name":"Deliu"},{"first_name":"Christoph","last_name":"Dotter","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-9033-9096","full_name":"Dotter, Christoph"},{"last_name":"Kara","first_name":"Majdi","full_name":"Kara, Majdi"},{"full_name":"Janiesch, Philipp","last_name":"Janiesch","first_name":"Philipp"},{"first_name":"Mariafrancesca","last_name":"Scalise","full_name":"Scalise, Mariafrancesca"},{"last_name":"Galluccio","first_name":"Michele","full_name":"Galluccio, Michele"},{"last_name":"Tesulov","first_name":"Mateja","full_name":"Tesulov, Mateja"},{"full_name":"Morelli, Emanuela","id":"3F4D1282-F248-11E8-B48F-1D18A9856A87","first_name":"Emanuela","last_name":"Morelli"},{"first_name":"Fatma","last_name":"Sönmez","full_name":"Sönmez, Fatma"},{"first_name":"Kaya","last_name":"Bilgüvar","full_name":"Bilgüvar, Kaya"},{"first_name":"Ryuichi","last_name":"Ohgaki","full_name":"Ohgaki, Ryuichi"},{"full_name":"Kanai, Yoshikatsu","first_name":"Yoshikatsu","last_name":"Kanai"},{"full_name":"Johansen, Anide","first_name":"Anide","last_name":"Johansen"},{"first_name":"Seham","last_name":"Esharif","full_name":"Esharif, Seham"},{"full_name":"Ben Omran, Tawfeg","first_name":"Tawfeg","last_name":"Ben Omran"},{"first_name":"Meral","last_name":"Topcu","full_name":"Topcu, Meral"},{"full_name":"Schlessinger, Avner","last_name":"Schlessinger","first_name":"Avner"},{"first_name":"Cesare","last_name":"Indiveri","full_name":"Indiveri, Cesare"},{"first_name":"Kent","last_name":"Duncan","full_name":"Duncan, Kent"},{"full_name":"Caglayan, Ahmet","last_name":"Caglayan","first_name":"Ahmet"},{"last_name":"Günel","first_name":"Murat","full_name":"Günel, Murat"},{"last_name":"Gleeson","first_name":"Joseph","full_name":"Gleeson, Joseph"},{"full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","first_name":"Gaia"}],"related_material":{"record":[{"status":"public","relation":"dissertation_contains","id":"395"}]},"date_created":"2018-12-11T11:50:35Z","date_updated":"2024-03-28T23:30:12Z","volume":167,"year":"2016","acknowledgement":"This work was supported by NICHD (P01HD070494) and SFARI (grant 275275) to J.G.G., and FWF (SFB35_3523) to G.N.\r\nWe thank A.C. Manzano, Mike Liu, and F. Marr for technical assistance, and R. Shigemoto and the IST Austria Electron Microscopy (EM) Facility for assistance. We acknowledge support from CIDR for genome-wide SNP analysis (X01HG008823) and Broad Institute Center for Mendelian Disorders (UM1HG008900 to D. MacArthur), the Yale Center for Mendelian Disorders (U54HG006504 to M.G.), the Gregory M. Kiez and Mehmet Kutman Foundation (M.G.), Italian Ministry of Instruction University and Research (PON01_00937 to C.I.), and NIH (R01-GM108911 to A.S.). This work was supported by NICHD (P01HD070494) and SFARI (grant 275275) to J.G.G., and FWF (SFB35_3523) to G.N.\r\n\r\n#EMFacility","publication_status":"published","publisher":"Cell Press","department":[{"_id":"GaNo"}],"file_date_updated":"2020-07-14T12:44:37Z","publist_id":"6170"},{"scopus_import":1,"has_accepted_license":"1","day":"21","citation":{"apa":"Andergassen, D., Dotter, C., Kulinski, T., Guenzl, P., Bammer, P., Barlow, D., … Hudson, Q. (2015). Allelome.PRO, a pipeline to define allele-specific genomic features from high-throughput sequencing data. Nucleic Acids Research. Oxford University Press. https://doi.org/10.1093/nar/gkv727","ieee":"D. Andergassen et al., “Allelome.PRO, a pipeline to define allele-specific genomic features from high-throughput sequencing data,” Nucleic Acids Research, vol. 43, no. 21. Oxford University Press, 2015.","ista":"Andergassen D, Dotter C, Kulinski T, Guenzl P, Bammer P, Barlow D, Pauler F, Hudson Q. 2015. Allelome.PRO, a pipeline to define allele-specific genomic features from high-throughput sequencing data. Nucleic Acids Research. 43(21), e146.","ama":"Andergassen D, Dotter C, Kulinski T, et al. Allelome.PRO, a pipeline to define allele-specific genomic features from high-throughput sequencing data. Nucleic Acids Research. 2015;43(21). doi:10.1093/nar/gkv727","chicago":"Andergassen, Daniel, Christoph Dotter, Tomasz Kulinski, Philipp Guenzl, Philipp Bammer, Denise Barlow, Florian Pauler, and Quanah Hudson. “Allelome.PRO, a Pipeline to Define Allele-Specific Genomic Features from High-Throughput Sequencing Data.” Nucleic Acids Research. Oxford University Press, 2015. https://doi.org/10.1093/nar/gkv727.","short":"D. Andergassen, C. Dotter, T. Kulinski, P. Guenzl, P. Bammer, D. Barlow, F. Pauler, Q. Hudson, Nucleic Acids Research 43 (2015).","mla":"Andergassen, Daniel, et al. “Allelome.PRO, a Pipeline to Define Allele-Specific Genomic Features from High-Throughput Sequencing Data.” Nucleic Acids Research, vol. 43, no. 21, e146, Oxford University Press, 2015, doi:10.1093/nar/gkv727."},"publication":"Nucleic Acids Research","date_published":"2015-07-21T00:00:00Z","type":"journal_article","issue":"21","abstract":[{"lang":"eng","text":"Detecting allelic biases from high-throughput sequencing data requires an approach that maximises sensitivity while minimizing false positives. Here, we present Allelome.PRO, an automated user-friendly bioinformatics pipeline, which uses high-throughput sequencing data from reciprocal crosses of two genetically distinct mouse strains to detect allele-specific expression and chromatin modifications. Allelome.PRO extends approaches used in previous studies that exclusively analyzed imprinted expression to give a complete picture of the ‘allelome’ by automatically categorising the allelic expression of all genes in a given cell type into imprinted, strain-biased, biallelic or non-informative. Allelome.PRO offers increased sensitivity to analyze lowly expressed transcripts, together with a robust false discovery rate empirically calculated from variation in the sequencing data. We used RNA-seq data from mouse embryonic fibroblasts from F1 reciprocal crosses to determine a biologically relevant allelic ratio cutoff, and define for the first time an entire allelome. Furthermore, we show that Allelome.PRO detects differential enrichment of H3K4me3 over promoters from ChIP-seq data validating the RNA-seq results. This approach can be easily extended to analyze histone marks of active enhancers, or transcription factor binding sites and therefore provides a powerful tool to identify candidate cis regulatory elements genome wide."}],"intvolume":" 43","status":"public","title":"Allelome.PRO, a pipeline to define allele-specific genomic features from high-throughput sequencing data","ddc":["570"],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"1497","file":[{"file_id":"5768","relation":"main_file","checksum":"385b83854fd0eb2e4f386867da2823e2","date_created":"2018-12-20T14:18:57Z","date_updated":"2020-07-14T12:44:58Z","access_level":"open_access","file_name":"2015_NucleicAcidsRes_Andergassen.pdf","creator":"dernst","file_size":6863297,"content_type":"application/pdf"}],"oa_version":"Published Version","month":"07","quality_controlled":"1","tmp":{"name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","short":"CC BY (4.0)","image":"/images/cc_by.png"},"oa":1,"language":[{"iso":"eng"}],"doi":"10.1093/nar/gkv727","article_number":"e146","publist_id":"5682","file_date_updated":"2020-07-14T12:44:58Z","publisher":"Oxford University Press","department":[{"_id":"GaNo"}],"publication_status":"published","year":"2015","acknowledgement":"Austrian Science Fund [FWF P25185-B22, FWF F4302- B09, FWFW1207-B09]. Funding for open access charge: Austrian Science Fund.\r\nWe thank Florian Breitwieser for advice during the early stages of this project. High-throughput sequencing was conducted by the Biomedical Sequencing Facility (BSF) at CeMM in Vienna.","volume":43,"date_created":"2018-12-11T11:52:22Z","date_updated":"2021-01-12T06:51:09Z","author":[{"full_name":"Andergassen, Daniel","last_name":"Andergassen","first_name":"Daniel"},{"full_name":"Dotter, Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87","last_name":"Dotter","first_name":"Christoph"},{"last_name":"Kulinski","first_name":"Tomasz","full_name":"Kulinski, Tomasz"},{"full_name":"Guenzl, Philipp","first_name":"Philipp","last_name":"Guenzl"},{"full_name":"Bammer, Philipp","first_name":"Philipp","last_name":"Bammer"},{"last_name":"Barlow","first_name":"Denise","full_name":"Barlow, Denise"},{"full_name":"Pauler, Florian","last_name":"Pauler","first_name":"Florian"},{"first_name":"Quanah","last_name":"Hudson","full_name":"Hudson, Quanah"}]},{"day":"15","page":"753 - 760","citation":{"ama":"Kuechler A, Zink A, Wieland T, et al. Loss-of-function variants of SETD5 cause intellectual disability and the core phenotype of microdeletion 3p25.3 syndrome. European Journal of Human Genetics. 2015;23(6):753-760. doi:10.1038/ejhg.2014.165","ieee":"A. Kuechler et al., “Loss-of-function variants of SETD5 cause intellectual disability and the core phenotype of microdeletion 3p25.3 syndrome,” European Journal of Human Genetics, vol. 23, no. 6. Nature Publishing Group, pp. 753–760, 2015.","apa":"Kuechler, A., Zink, A., Wieland, T., Lüdecke, H., Cremer, K., Salviati, L., … Engels, H. (2015). Loss-of-function variants of SETD5 cause intellectual disability and the core phenotype of microdeletion 3p25.3 syndrome. European Journal of Human Genetics. Nature Publishing Group. https://doi.org/10.1038/ejhg.2014.165","ista":"Kuechler A, Zink A, Wieland T, Lüdecke H, Cremer K, Salviati L, Magini P, Najafi K, Zweier C, Czeschik J, Aretz S, Endele S, Tamburrino F, Pinato C, Clementi M, Gundlach J, Maylahn C, Mazzanti L, Wohlleber E, Schwarzmayr T, Kariminejad R, Schlessinger A, Wieczorek D, Strom T, Novarino G, Engels H. 2015. Loss-of-function variants of SETD5 cause intellectual disability and the core phenotype of microdeletion 3p25.3 syndrome. European Journal of Human Genetics. 23(6), 753–760.","short":"A. Kuechler, A. Zink, T. Wieland, H. Lüdecke, K. Cremer, L. Salviati, P. Magini, K. Najafi, C. Zweier, J. Czeschik, S. Aretz, S. Endele, F. Tamburrino, C. Pinato, M. Clementi, J. Gundlach, C. Maylahn, L. Mazzanti, E. Wohlleber, T. Schwarzmayr, R. Kariminejad, A. Schlessinger, D. Wieczorek, T. Strom, G. Novarino, H. Engels, European Journal of Human Genetics 23 (2015) 753–760.","mla":"Kuechler, Alma, et al. “Loss-of-Function Variants of SETD5 Cause Intellectual Disability and the Core Phenotype of Microdeletion 3p25.3 Syndrome.” European Journal of Human Genetics, vol. 23, no. 6, Nature Publishing Group, 2015, pp. 753–60, doi:10.1038/ejhg.2014.165.","chicago":"Kuechler, Alma, Alexander Zink, Thomas Wieland, Hermann Lüdecke, Kirsten Cremer, Leonardo Salviati, Pamela Magini, et al. “Loss-of-Function Variants of SETD5 Cause Intellectual Disability and the Core Phenotype of Microdeletion 3p25.3 Syndrome.” European Journal of Human Genetics. Nature Publishing Group, 2015. https://doi.org/10.1038/ejhg.2014.165."},"publication":"European Journal of Human Genetics","date_published":"2015-06-15T00:00:00Z","type":"journal_article","issue":"6","abstract":[{"lang":"eng","text":"Intellectual disability (ID) has an estimated prevalence of 2-3%. Due to its extreme heterogeneity, the genetic basis of ID remains elusive in many cases. Recently, whole exome sequencing (WES) studies revealed that a large proportion of sporadic cases are caused by de novo gene variants. To identify further genes involved in ID, we performed WES in 250 patients with unexplained ID and their unaffected parents and included exomes of 51 previously sequenced child-parents trios in the analysis. Exome analysis revealed de novo intragenic variants in SET domain-containing 5 (SETD5) in two patients. One patient carried a nonsense variant, and the other an 81 bp deletion located across a splice-donor site. Chromosomal microarray diagnostics further identified four de novo non-recurrent microdeletions encompassing SETD5. CRISPR/Cas9 mutation modelling of the two intragenic variants demonstrated nonsense-mediated decay of the resulting transcripts, pointing to a loss-of-function (LoF) and haploinsufficiency as the common disease-causing mechanism of intragenic SETD5 sequence variants and SETD5-containing microdeletions. In silico domain prediction of SETD5, a predicted SET domain-containing histone methyltransferase (HMT), substantiated the presence of a SET domain and identified a novel putative PHD domain, strengthening a functional link to well-known histone-modifying ID genes. All six patients presented with ID and certain facial dysmorphisms, suggesting that SETD5 sequence variants contribute substantially to the microdeletion 3p25.3 phenotype. The present report of two SETD5 LoF variants in 301 patients demonstrates a prevalence of 0.7% and thus SETD5 variants as a relatively frequent cause of ID."}],"intvolume":" 23","status":"public","title":"Loss-of-function variants of SETD5 cause intellectual disability and the core phenotype of microdeletion 3p25.3 syndrome","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","_id":"1789","oa_version":"Submitted Version","month":"06","quality_controlled":"1","external_id":{"pmid":["25138099"]},"oa":1,"main_file_link":[{"url":"http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4795044/","open_access":"1"}],"language":[{"iso":"eng"}],"doi":"10.1038/ejhg.2014.165","publist_id":"5324","department":[{"_id":"GaNo"}],"publisher":"Nature Publishing Group","publication_status":"published","pmid":1,"year":"2015","volume":23,"date_created":"2018-12-11T11:54:01Z","date_updated":"2021-01-12T06:53:12Z","author":[{"first_name":"Alma","last_name":"Kuechler","full_name":"Kuechler, Alma"},{"full_name":"Zink, Alexander","first_name":"Alexander","last_name":"Zink"},{"full_name":"Wieland, Thomas","first_name":"Thomas","last_name":"Wieland"},{"last_name":"Lüdecke","first_name":"Hermann","full_name":"Lüdecke, Hermann"},{"last_name":"Cremer","first_name":"Kirsten","full_name":"Cremer, Kirsten"},{"full_name":"Salviati, Leonardo","last_name":"Salviati","first_name":"Leonardo"},{"full_name":"Magini, Pamela","last_name":"Magini","first_name":"Pamela"},{"last_name":"Najafi","first_name":"Kimia","full_name":"Najafi, Kimia"},{"first_name":"Christiane","last_name":"Zweier","full_name":"Zweier, Christiane"},{"last_name":"Czeschik","first_name":"Johanna","full_name":"Czeschik, Johanna"},{"first_name":"Stefan","last_name":"Aretz","full_name":"Aretz, Stefan"},{"first_name":"Sabine","last_name":"Endele","full_name":"Endele, Sabine"},{"first_name":"Federica","last_name":"Tamburrino","full_name":"Tamburrino, Federica"},{"first_name":"Claudia","last_name":"Pinato","full_name":"Pinato, Claudia"},{"last_name":"Clementi","first_name":"Maurizio","full_name":"Clementi, Maurizio"},{"last_name":"Gundlach","first_name":"Jasmin","full_name":"Gundlach, Jasmin"},{"full_name":"Maylahn, Carina","last_name":"Maylahn","first_name":"Carina"},{"first_name":"Laura","last_name":"Mazzanti","full_name":"Mazzanti, Laura"},{"last_name":"Wohlleber","first_name":"Eva","full_name":"Wohlleber, Eva"},{"full_name":"Schwarzmayr, Thomas","last_name":"Schwarzmayr","first_name":"Thomas"},{"first_name":"Roxana","last_name":"Kariminejad","full_name":"Kariminejad, Roxana"},{"full_name":"Schlessinger, Avner","last_name":"Schlessinger","first_name":"Avner"},{"full_name":"Wieczorek, Dagmar","first_name":"Dagmar","last_name":"Wieczorek"},{"full_name":"Strom, Tim","first_name":"Tim","last_name":"Strom"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","first_name":"Gaia","last_name":"Novarino","full_name":"Novarino, Gaia"},{"full_name":"Engels, Hartmut","last_name":"Engels","first_name":"Hartmut"}]},{"article_processing_charge":"No","day":"31","scopus_import":1,"date_published":"2014-01-31T00:00:00Z","citation":{"chicago":"Novarino, Gaia, Ali Fenstermaker, Maha Zaki, Matan Hofree, Jennifer Silhavy, Andrew Heiberg, Mostafa Abdellateef, et al. “Exome Sequencing Links Corticospinal Motor Neuron Disease to Common Neurodegenerative Disorders.” Science. American Association for the Advancement of Science, 2014. https://doi.org/10.1126/science.1247363.","short":"G. Novarino, A. Fenstermaker, M. Zaki, M. Hofree, J. Silhavy, A. Heiberg, M. Abdellateef, B. Rosti, E. Scott, L. Mansour, A. Masri, H. Kayserili, J. Al Aama, G. Abdel Salam, A. Karminejad, M. Kara, B. Kara, B. Bozorgmehri, T. Ben Omran, F. Mojahedi, I. Mahmoud, N. Bouslam, A. Bouhouche, A. Benomar, S. Hanein, L. Raymond, S. Forlani, M. Mascaro, L. Selim, N. Shehata, N. Al Allawi, P. Bindu, M. Azam, M. Günel, A. Caglayan, K. Bilgüvar, A. Tolun, M. Issa, J. Schroth, E. Spencer, R. Rosti, N. Akizu, K. Vaux, A. Johansen, A. Koh, H. Megahed, A. Dürr, A. Brice, G. Stévanin, S. Gabriel, T. Ideker, J. Gleeson, Science 343 (2014) 506–511.","mla":"Novarino, Gaia, et al. “Exome Sequencing Links Corticospinal Motor Neuron Disease to Common Neurodegenerative Disorders.” Science, vol. 343, no. 6170, American Association for the Advancement of Science, 2014, pp. 506–11, doi:10.1126/science.1247363.","ieee":"G. Novarino et al., “Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders,” Science, vol. 343, no. 6170. American Association for the Advancement of Science, pp. 506–511, 2014.","apa":"Novarino, G., Fenstermaker, A., Zaki, M., Hofree, M., Silhavy, J., Heiberg, A., … Gleeson, J. (2014). Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.1247363","ista":"Novarino G, Fenstermaker A, Zaki M, Hofree M, Silhavy J, Heiberg A, Abdellateef M, Rosti B, Scott E, Mansour L, Masri A, Kayserili H, Al Aama J, Abdel Salam G, Karminejad A, Kara M, Kara B, Bozorgmehri B, Ben Omran T, Mojahedi F, Mahmoud I, Bouslam N, Bouhouche A, Benomar A, Hanein S, Raymond L, Forlani S, Mascaro M, Selim L, Shehata N, Al Allawi N, Bindu P, Azam M, Günel M, Caglayan A, Bilgüvar K, Tolun A, Issa M, Schroth J, Spencer E, Rosti R, Akizu N, Vaux K, Johansen A, Koh A, Megahed H, Dürr A, Brice A, Stévanin G, Gabriel S, Ideker T, Gleeson J. 2014. Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders. Science. 343(6170), 506–511.","ama":"Novarino G, Fenstermaker A, Zaki M, et al. Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders. Science. 2014;343(6170):506-511. doi:10.1126/science.1247363"},"publication":"Science","page":"506 - 511","article_type":"original","issue":"6170","abstract":[{"text":"Hereditary spastic paraplegias (HSPs) are neurodegenerative motor neuron diseases characterized by progressive age-dependent loss of corticospinal motor tract function. Although the genetic basis is partly understood, only a fraction of cases can receive a genetic diagnosis, and a global view of HSP is lacking. By using whole-exome sequencing in combination with network analysis, we identified 18 previously unknown putative HSP genes and validated nearly all of these genes functionally or genetically. The pathways highlighted by these mutations link HSP to cellular transport, nucleotide metabolism, and synapse and axon development. Network analysis revealed a host of further candidate genes, of which three were mutated in our cohort. Our analysis links HSP to other neurodegenerative disorders and can facilitate gene discovery and mechanistic understanding of disease.","lang":"eng"}],"type":"journal_article","oa_version":"Submitted Version","_id":"1916","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","intvolume":" 343","status":"public","title":"Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders","month":"01","doi":"10.1126/science.1247363","language":[{"iso":"eng"}],"oa":1,"external_id":{"pmid":["24482476"]},"main_file_link":[{"open_access":"1","url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4157572/"}],"quality_controlled":"1","publist_id":"5178","author":[{"first_name":"Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"},{"last_name":"Fenstermaker","first_name":"Ali","full_name":"Fenstermaker, Ali"},{"last_name":"Zaki","first_name":"Maha","full_name":"Zaki, Maha"},{"full_name":"Hofree, Matan","first_name":"Matan","last_name":"Hofree"},{"first_name":"Jennifer","last_name":"Silhavy","full_name":"Silhavy, Jennifer"},{"full_name":"Heiberg, Andrew","last_name":"Heiberg","first_name":"Andrew"},{"full_name":"Abdellateef, Mostafa","last_name":"Abdellateef","first_name":"Mostafa"},{"full_name":"Rosti, Başak","first_name":"Başak","last_name":"Rosti"},{"last_name":"Scott","first_name":"Eric","full_name":"Scott, Eric"},{"full_name":"Mansour, Lobna","first_name":"Lobna","last_name":"Mansour"},{"full_name":"Masri, Amira","last_name":"Masri","first_name":"Amira"},{"full_name":"Kayserili, Hülya","first_name":"Hülya","last_name":"Kayserili"},{"first_name":"Jumana","last_name":"Al Aama","full_name":"Al Aama, Jumana"},{"first_name":"Ghada","last_name":"Abdel Salam","full_name":"Abdel Salam, Ghada"},{"last_name":"Karminejad","first_name":"Ariana","full_name":"Karminejad, Ariana"},{"last_name":"Kara","first_name":"Majdi","full_name":"Kara, Majdi"},{"last_name":"Kara","first_name":"Bülent","full_name":"Kara, Bülent"},{"last_name":"Bozorgmehri","first_name":"Bita","full_name":"Bozorgmehri, Bita"},{"full_name":"Ben Omran, Tawfeg","last_name":"Ben Omran","first_name":"Tawfeg"},{"full_name":"Mojahedi, Faezeh","last_name":"Mojahedi","first_name":"Faezeh"},{"last_name":"Mahmoud","first_name":"Iman","full_name":"Mahmoud, Iman"},{"full_name":"Bouslam, Naïma","first_name":"Naïma","last_name":"Bouslam"},{"full_name":"Bouhouche, Ahmed","last_name":"Bouhouche","first_name":"Ahmed"},{"first_name":"Ali","last_name":"Benomar","full_name":"Benomar, Ali"},{"full_name":"Hanein, Sylvain","first_name":"Sylvain","last_name":"Hanein"},{"first_name":"Laure","last_name":"Raymond","full_name":"Raymond, Laure"},{"full_name":"Forlani, Sylvie","last_name":"Forlani","first_name":"Sylvie"},{"full_name":"Mascaro, Massimo","last_name":"Mascaro","first_name":"Massimo"},{"full_name":"Selim, Laila","last_name":"Selim","first_name":"Laila"},{"first_name":"Nabil","last_name":"Shehata","full_name":"Shehata, Nabil"},{"full_name":"Al Allawi, Nasir","first_name":"Nasir","last_name":"Al Allawi"},{"full_name":"Bindu, Parayil","last_name":"Bindu","first_name":"Parayil"},{"full_name":"Azam, Matloob","first_name":"Matloob","last_name":"Azam"},{"full_name":"Günel, Murat","first_name":"Murat","last_name":"Günel"},{"first_name":"Ahmet","last_name":"Caglayan","full_name":"Caglayan, Ahmet"},{"first_name":"Kaya","last_name":"Bilgüvar","full_name":"Bilgüvar, Kaya"},{"full_name":"Tolun, Aslihan","last_name":"Tolun","first_name":"Aslihan"},{"last_name":"Issa","first_name":"Mahmoud","full_name":"Issa, Mahmoud"},{"full_name":"Schroth, Jana","last_name":"Schroth","first_name":"Jana"},{"first_name":"Emily","last_name":"Spencer","full_name":"Spencer, Emily"},{"full_name":"Rosti, Rasim","first_name":"Rasim","last_name":"Rosti"},{"full_name":"Akizu, Naiara","first_name":"Naiara","last_name":"Akizu"},{"first_name":"Keith","last_name":"Vaux","full_name":"Vaux, Keith"},{"full_name":"Johansen, Anide","last_name":"Johansen","first_name":"Anide"},{"last_name":"Koh","first_name":"Alice","full_name":"Koh, Alice"},{"full_name":"Megahed, Hisham","last_name":"Megahed","first_name":"Hisham"},{"first_name":"Alexandra","last_name":"Dürr","full_name":"Dürr, Alexandra"},{"first_name":"Alexis","last_name":"Brice","full_name":"Brice, Alexis"},{"full_name":"Stévanin, Giovanni","last_name":"Stévanin","first_name":"Giovanni"},{"full_name":"Gabriel, Stacy","first_name":"Stacy","last_name":"Gabriel"},{"full_name":"Ideker, Trey","last_name":"Ideker","first_name":"Trey"},{"first_name":"Joseph","last_name":"Gleeson","full_name":"Gleeson, Joseph"}],"volume":343,"date_updated":"2021-01-12T06:54:03Z","date_created":"2018-12-11T11:54:42Z","pmid":1,"acknowledgement":"Supported by the Deutsche Forschungsgemeinschaft (G.N.)","year":"2014","department":[{"_id":"GaNo"}],"publisher":"American Association for the Advancement of Science","publication_status":"published"}]