[{"oa_version":"Published Version","pmid":1,"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"}],"intvolume":" 41","month":"07","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221757/","open_access":"1"}],"scopus_import":"1","language":[{"iso":"eng"}],"publication_status":"published","publication_identifier":{"issn":["0271-678x"],"eissn":["1559-7016"]},"volume":41,"issue":"7","_id":"8730","status":"public","type":"journal_article","article_type":"original","date_updated":"2023-10-18T06:45:30Z","department":[{"_id":"GaNo"}],"oa":1,"publisher":"SAGE Publications","quality_controlled":"1","publication":"Journal of Cerebral Blood Flow and Metabolism","day":"01","year":"2021","isi":1,"date_created":"2020-11-06T08:39:01Z","date_published":"2021-07-01T00:00:00Z","doi":"10.1177/0271678X20965500","page":"1634-1646","user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","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.","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.","ama":"Tournier N, Goutal S, Mairinger S, et al. Complete inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion of erlotinib and tariquidar to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib. Journal of Cerebral Blood Flow and Metabolism. 2021;41(7):1634-1646. doi:10.1177/0271678X20965500","apa":"Tournier, N., Goutal, S., Mairinger, S., Lozano, I., Filip, T., Sauberer, M., … Langer, O. (2021). Complete inhibition of ABCB1 and ABCG2 at the blood-brain barrier by co-infusion of erlotinib and tariquidar to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib. Journal of Cerebral Blood Flow and Metabolism. SAGE Publications. https://doi.org/10.1177/0271678X20965500","chicago":"Tournier, N, S Goutal, S Mairinger, IH Lozano, T Filip, M Sauberer, F Caillé, et al. “Complete Inhibition of ABCB1 and ABCG2 at the Blood-Brain Barrier by Co-Infusion of Erlotinib and Tariquidar to Improve Brain Delivery of the Model ABCB1/ABCG2 Substrate [11C]Erlotinib.” Journal of Cerebral Blood Flow and Metabolism. SAGE Publications, 2021. https://doi.org/10.1177/0271678X20965500.","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."},"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","article_processing_charge":"No","external_id":{"isi":["000664214100012"],"pmid":["33081568"]},"author":[{"last_name":"Tournier","full_name":"Tournier, N","first_name":"N"},{"last_name":"Goutal","full_name":"Goutal, S","first_name":"S"},{"first_name":"S","last_name":"Mairinger","full_name":"Mairinger, S"},{"full_name":"Lozano, IH","last_name":"Lozano","first_name":"IH"},{"full_name":"Filip, T","last_name":"Filip","first_name":"T"},{"first_name":"M","last_name":"Sauberer","full_name":"Sauberer, M"},{"first_name":"F","last_name":"Caillé","full_name":"Caillé, F"},{"first_name":"L","last_name":"Breuil","full_name":"Breuil, L"},{"first_name":"J","full_name":"Stanek, J","last_name":"Stanek"},{"last_name":"Freeman","full_name":"Freeman, AF","first_name":"AF"},{"last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia"},{"first_name":"C","full_name":"Truillet, C","last_name":"Truillet"},{"last_name":"Wanek","full_name":"Wanek, T","first_name":"T"},{"full_name":"Langer, O","last_name":"Langer","first_name":"O"}]},{"oa":1,"publisher":"Springer Nature","quality_controlled":"1","acknowledgement":"We thank A. Coll Manzano, F. Freeman, M. Ladron de Guevara, and A. Ç. Yahya for technical assistance, S. Deixler, A. Lepold, and A. Schlerka for the management of our animal colony, as well as M. Schunn and the Preclinical Facility team for technical assistance. We thank K. Heesom and her team at the University of Bristol Proteomics Facility for the proteomics sample preparation, data generation, and analysis support. We thank Y. B. Simon for kindly providing the plasmid for lentiviral labeling. Further, we thank M. Sixt for his advice regarding cell migration and the fruitful discussions. This work was supported by the ISTPlus postdoctoral fellowship (Grant Agreement No. 754411) to B.B., by the European Union’s Horizon 2020 research and innovation program (ERC) grant 715508 (REVERSEAUTISM), and by the Austrian Science Fund (FWF) to G.N. (DK W1232-B24 and SFB F7807-B) and to J.G.D (I3600-B27).","date_created":"2021-05-28T11:49:46Z","date_published":"2021-05-24T00:00:00Z","doi":"10.1038/s41467-021-23123-x","publication":"Nature Communications","day":"24","year":"2021","isi":1,"has_accepted_license":"1","project":[{"name":"ISTplus - Postdoctoral Fellowships","grant_number":"754411","_id":"260C2330-B435-11E9-9278-68D0E5697425","call_identifier":"H2020"},{"grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models","call_identifier":"H2020","_id":"25444568-B435-11E9-9278-68D0E5697425"},{"name":"Molecular Drug Targets","grant_number":"W1232-B24","call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425"},{"name":"Neural stem cells in autism and epilepsy","grant_number":"F07807","_id":"05A0D778-7A3F-11EA-A408-12923DDC885E"},{"call_identifier":"FWF","_id":"265CB4D0-B435-11E9-9278-68D0E5697425","grant_number":"I03600","name":"Optical control of synaptic function via adhesion molecules"}],"article_number":"3058","title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","external_id":{"isi":["000658769900010"]},"article_processing_charge":"No","author":[{"first_name":"Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","full_name":"Morandell, Jasmin","last_name":"Morandell"},{"full_name":"Schwarz, Lena A","last_name":"Schwarz","id":"29A8453C-F248-11E8-B48F-1D18A9856A87","first_name":"Lena A"},{"full_name":"Basilico, Bernadette","orcid":"0000-0003-1843-3173","last_name":"Basilico","first_name":"Bernadette","id":"36035796-5ACA-11E9-A75E-7AF2E5697425"},{"last_name":"Tasciyan","full_name":"Tasciyan, Saren","orcid":"0000-0003-1671-393X","first_name":"Saren","id":"4323B49C-F248-11E8-B48F-1D18A9856A87"},{"last_name":"Dimchev","orcid":"0000-0001-8370-6161","full_name":"Dimchev, Georgi A","id":"38C393BE-F248-11E8-B48F-1D18A9856A87","first_name":"Georgi A"},{"id":"2A103192-F248-11E8-B48F-1D18A9856A87","first_name":"Armel","full_name":"Nicolas, Armel","last_name":"Nicolas"},{"id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87","first_name":"Christoph M","full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","last_name":"Sommer"},{"first_name":"Caroline","id":"382077BA-F248-11E8-B48F-1D18A9856A87","full_name":"Kreuzinger, Caroline","last_name":"Kreuzinger"},{"orcid":"0000-0002-9033-9096","full_name":"Dotter, Christoph","last_name":"Dotter","first_name":"Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87"},{"id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","first_name":"Lisa","last_name":"Knaus","full_name":"Knaus, Lisa"},{"full_name":"Dobler, Zoe","last_name":"Dobler","id":"D23090A2-9057-11EA-883A-A8396FC7A38F","first_name":"Zoe"},{"first_name":"Emanuele","full_name":"Cacci, Emanuele","last_name":"Cacci"},{"last_name":"Schur","full_name":"Schur, Florian KM","orcid":"0000-0003-4790-8078","first_name":"Florian KM","id":"48AD8942-F248-11E8-B48F-1D18A9856A87"},{"id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","first_name":"Johann G","orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G","last_name":"Danzl"},{"orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","last_name":"Novarino","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"chicago":"Morandell, Jasmin, Lena A Schwarz, Bernadette Basilico, Saren Tasciyan, Georgi A Dimchev, Armel Nicolas, Christoph M Sommer, et al. “Cul3 Regulates Cytoskeleton Protein Homeostasis and Cell Migration during a Critical Window of Brain Development.” Nature Communications. Springer Nature, 2021. https://doi.org/10.1038/s41467-021-23123-x.","ista":"Morandell J, Schwarz LA, Basilico B, Tasciyan S, Dimchev GA, Nicolas A, Sommer CM, Kreuzinger C, Dotter C, Knaus L, Dobler Z, Cacci E, Schur FK, Danzl JG, Novarino G. 2021. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. 12(1), 3058.","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.","ama":"Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. 2021;12(1). doi:10.1038/s41467-021-23123-x","apa":"Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Dimchev, G. A., Nicolas, A., … Novarino, G. (2021). Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. Nature Communications. Springer Nature. https://doi.org/10.1038/s41467-021-23123-x","ieee":"J. Morandell et al., “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” Nature Communications, vol. 12, no. 1. Springer Nature, 2021.","short":"J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, G.A. Dimchev, A. Nicolas, C.M. Sommer, C. Kreuzinger, C. Dotter, L. Knaus, Z. Dobler, E. Cacci, F.K. Schur, J.G. Danzl, G. Novarino, Nature Communications 12 (2021)."},"intvolume":" 12","month":"05","oa_version":"Published Version","acknowledged_ssus":[{"_id":"PreCl"}],"abstract":[{"lang":"eng","text":"De novo loss of function mutations in the ubiquitin ligase-encoding gene Cullin3 lead to autism spectrum disorder (ASD). In mouse, constitutive haploinsufficiency leads to motor coordination deficits as well as ASD-relevant social and cognitive impairments. However, induction of Cul3 haploinsufficiency later in life does not lead to ASD-relevant behaviors, pointing to an important role of Cul3 during a critical developmental window. Here we show that Cul3 is essential to regulate neuronal migration and, therefore, constitutive Cul3 heterozygous mutant mice display cortical lamination abnormalities. At the molecular level, we found that Cul3 controls neuronal migration by tightly regulating the amount of Plastin3 (Pls3), a previously unrecognized player of neural migration. Furthermore, we found that Pls3 cell-autonomously regulates cell migration by regulating actin cytoskeleton organization, and its levels are inversely proportional to neural migration speed. Finally, we provide evidence that cellular phenotypes associated with autism-linked gene haploinsufficiency can be rescued by transcriptional activation of the intact allele in vitro, offering a proof of concept for a potential therapeutic approach for ASDs."}],"ec_funded":1,"issue":"1","volume":12,"related_material":{"link":[{"url":"https://ist.ac.at/en/news/defective-gene-slows-down-brain-cells/","relation":"press_release"}],"record":[{"relation":"earlier_version","status":"public","id":"7800"},{"id":"12401","status":"public","relation":"dissertation_contains"}]},"language":[{"iso":"eng"}],"file":[{"checksum":"337e0f7959c35ec959984cacdcb472ba","file_id":"9430","success":1,"access_level":"open_access","relation":"main_file","content_type":"application/pdf","date_created":"2021-05-28T12:39:43Z","file_name":"2021_NatureCommunications_Morandell.pdf","creator":"kschuh","date_updated":"2021-05-28T12:39:43Z","file_size":9358599}],"publication_status":"published","publication_identifier":{"eissn":["2041-1723"]},"keyword":["General Biochemistry","Genetics and Molecular Biology"],"status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","article_type":"original","_id":"9429","file_date_updated":"2021-05-28T12:39:43Z","department":[{"_id":"GaNo"},{"_id":"JoDa"},{"_id":"FlSc"},{"_id":"MiSi"},{"_id":"LifeSc"},{"_id":"Bio"}],"ddc":["572"],"date_updated":"2024-03-27T23:30:23Z"},{"oa_version":"None","pmid":1,"abstract":[{"lang":"eng","text":"In recent years, many genes have been associated with chromatinopathies classified as “Cornelia de Lange Syndrome‐like.” It is known that the phenotype of these patients becomes less recognizable, overlapping to features characteristic of other syndromes caused by genetic variants affecting different regulators of chromatin structure and function. Therefore, Cornelia de Lange syndrome diagnosis might be arduous due to the seldom discordance between unexpected molecular diagnosis and clinical evaluation. Here, we review the molecular features of Cornelia de Lange syndrome, supporting the hypothesis that “CdLS‐like syndromes” are part of a larger “rare disease family” sharing multiple clinical features and common disrupted molecular pathways."}],"intvolume":" 97","month":"01","scopus_import":"1","language":[{"iso":"eng"}],"publication_status":"published","publication_identifier":{"issn":["0009-9163"],"eissn":["1399-0004"]},"volume":97,"issue":"1","_id":"7149","status":"public","article_type":"review","type":"journal_article","date_updated":"2023-08-17T14:06:20Z","department":[{"_id":"GaNo"}],"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","publisher":"Wiley","quality_controlled":"1","publication":"Clinical Genetics","day":"01","year":"2020","isi":1,"date_created":"2019-12-04T16:10:59Z","doi":"10.1111/cge.13674","date_published":"2020-01-01T00:00:00Z","page":"3-11","user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","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.","ieee":"L. Avagliano et al., “Chromatinopathies: A focus on Cornelia de Lange syndrome,” Clinical Genetics, vol. 97, no. 1. Wiley, pp. 3–11, 2020.","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","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","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.","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."},"title":"Chromatinopathies: A focus on Cornelia de Lange syndrome","external_id":{"pmid":["31721174"],"isi":["000562561800001"]},"article_processing_charge":"No","author":[{"first_name":"Laura","full_name":"Avagliano, Laura","last_name":"Avagliano"},{"last_name":"Parenti","full_name":"Parenti, Ilaria","first_name":"Ilaria","id":"D93538B0-5B71-11E9-AC62-02EBE5697425"},{"first_name":"Paolo","full_name":"Grazioli, Paolo","last_name":"Grazioli"},{"first_name":"Elisabetta","full_name":"Di Fede, Elisabetta","last_name":"Di Fede"},{"last_name":"Parodi","full_name":"Parodi, Chiara","first_name":"Chiara"},{"full_name":"Mariani, Milena","last_name":"Mariani","first_name":"Milena"},{"first_name":"Frank J.","last_name":"Kaiser","full_name":"Kaiser, Frank J."},{"first_name":"Angelo","last_name":"Selicorni","full_name":"Selicorni, Angelo"},{"last_name":"Gervasini","full_name":"Gervasini, Cristina","first_name":"Cristina"},{"first_name":"Valentina","last_name":"Massa","full_name":"Massa, Valentina"}]},{"department":[{"_id":"GaNo"}],"file_date_updated":"2020-07-14T12:47:59Z","ddc":["570"],"date_updated":"2023-08-18T06:35:41Z","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","article_type":"original","_id":"7488","volume":21,"issue":"3","language":[{"iso":"eng"}],"file":[{"file_id":"7496","checksum":"0e6658c4fe329d55d4d9bef01c5b15d0","content_type":"application/pdf","relation":"main_file","access_level":"open_access","file_name":"2020_IntMolecSciences_Latorre.pdf","date_created":"2020-02-18T07:49:22Z","file_size":4271234,"date_updated":"2020-07-14T12:47:59Z","creator":"dernst"}],"publication_status":"published","publication_identifier":{"eissn":["14220067"],"issn":["16616596"]},"intvolume":" 21","month":"02","scopus_import":"1","oa_version":"Published Version","abstract":[{"lang":"eng","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."}],"title":"Evaluating Face2Gene as a tool to identify Cornelia de Lange syndrome by facial phenotypes","article_processing_charge":"No","external_id":{"isi":["000522551606028"]},"author":[{"last_name":"Latorre-Pellicer","full_name":"Latorre-Pellicer, Ana","first_name":"Ana"},{"full_name":"Ascaso, Ángela","last_name":"Ascaso","first_name":"Ángela"},{"first_name":"Laura","last_name":"Trujillano","full_name":"Trujillano, Laura"},{"last_name":"Gil-Salvador","full_name":"Gil-Salvador, Marta","first_name":"Marta"},{"first_name":"Maria","full_name":"Arnedo, 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","full_name":"Marcos-Alcalde, Iñigo","first_name":"Iñigo"},{"first_name":"Ilaria","id":"D93538B0-5B71-11E9-AC62-02EBE5697425","last_name":"Parenti","full_name":"Parenti, Ilaria"},{"first_name":"Gloria","full_name":"Bueno-Lozano, Gloria","last_name":"Bueno-Lozano"},{"first_name":"Antonio","full_name":"Musio, Antonio","last_name":"Musio"},{"first_name":"Beatriz","last_name":"Puisac","full_name":"Puisac, Beatriz"},{"first_name":"Frank J.","last_name":"Kaiser","full_name":"Kaiser, Frank J."},{"first_name":"Feliciano J.","full_name":"Ramos, Feliciano J.","last_name":"Ramos"},{"last_name":"Gómez-Puertas","full_name":"Gómez-Puertas, Paulino","first_name":"Paulino"},{"first_name":"Juan","full_name":"Pié, Juan","last_name":"Pié"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","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.","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.","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).","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","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","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.","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."},"article_number":"1042","date_created":"2020-02-16T23:00:49Z","date_published":"2020-02-04T00:00:00Z","doi":"10.3390/ijms21031042","publication":"International Journal of Molecular Sciences","day":"04","year":"2020","isi":1,"has_accepted_license":"1","oa":1,"publisher":"MDPI","quality_controlled":"1"},{"date_updated":"2023-08-18T07:07:36Z","ddc":["570"],"file_date_updated":"2020-07-14T12:48:00Z","department":[{"_id":"GaNo"}],"_id":"7586","tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"article_type":"original","type":"journal_article","status":"public","publication_status":"published","publication_identifier":{"eissn":["14602075"],"issn":["02614189"]},"language":[{"iso":"eng"}],"file":[{"date_created":"2020-03-23T13:51:11Z","file_name":"2020_EMBO_Weinert.pdf","creator":"dernst","date_updated":"2020-07-14T12:48:00Z","file_size":12243278,"checksum":"82750a7a93e3740decbce8474004111a","file_id":"7615","access_level":"open_access","relation":"main_file","content_type":"application/pdf"}],"volume":39,"abstract":[{"text":"CLC chloride/proton exchangers may support acidification of endolysosomes and raise their luminal Cl− concentration. Disruption of endosomal ClC‐3 causes severe neurodegeneration. To assess the importance of ClC‐3 Cl−/H+ exchange, we now generate Clcn3unc/unc mice in which ClC‐3 is converted into a Cl− channel. Unlike Clcn3−/− mice, Clcn3unc/unc mice appear normal owing to compensation by ClC‐4 with which ClC‐3 forms heteromers. ClC‐4 protein levels are strongly reduced in Clcn3−/−, but not in Clcn3unc/unc mice because ClC‐3unc binds and stabilizes ClC‐4 like wild‐type ClC‐3. Although mice lacking ClC‐4 appear healthy, its absence in Clcn3unc/unc/Clcn4−/− mice entails even stronger neurodegeneration than observed in Clcn3−/− mice. A fraction of ClC‐3 is found on synaptic vesicles, but miniature postsynaptic currents and synaptic vesicle acidification are not affected in Clcn3unc/unc or Clcn3−/− mice before neurodegeneration sets in. Both, Cl−/H+‐exchange activity and the stabilizing effect on ClC‐4, are central to the biological function of ClC‐3.","lang":"eng"}],"pmid":1,"oa_version":"Published Version","scopus_import":"1","intvolume":" 39","month":"03","citation":{"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","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","ieee":"S. Weinert et al., “Uncoupling endosomal CLC chloride/proton exchange causes severe neurodegeneration,” EMBO Journal, vol. 39. EMBO Press, 2020.","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).","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.","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.","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."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_processing_charge":"No","external_id":{"isi":["000517335000001"],"pmid":["32118314"]},"author":[{"last_name":"Weinert","full_name":"Weinert, Stefanie","first_name":"Stefanie"},{"last_name":"Gimber","full_name":"Gimber, Niclas","first_name":"Niclas"},{"first_name":"Dorothea","last_name":"Deuschel","full_name":"Deuschel, Dorothea"},{"first_name":"Till","last_name":"Stuhlmann","full_name":"Stuhlmann, Till"},{"last_name":"Puchkov","full_name":"Puchkov, Dmytro","first_name":"Dmytro"},{"first_name":"Zohreh","last_name":"Farsi","full_name":"Farsi, Zohreh"},{"full_name":"Ludwig, Carmen F.","last_name":"Ludwig","first_name":"Carmen F."},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178"},{"first_name":"Karen I.","full_name":"López-Cayuqueo, Karen I.","last_name":"López-Cayuqueo"},{"first_name":"Rosa","last_name":"Planells-Cases","full_name":"Planells-Cases, Rosa"},{"last_name":"Jentsch","full_name":"Jentsch, Thomas J.","first_name":"Thomas J."}],"title":"Uncoupling endosomal CLC chloride/proton exchange causes severe neurodegeneration","article_number":"e103358","year":"2020","has_accepted_license":"1","isi":1,"publication":"EMBO Journal","day":"02","date_created":"2020-03-15T23:00:55Z","date_published":"2020-03-02T00:00:00Z","doi":"10.15252/embj.2019103358","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.","oa":1,"quality_controlled":"1","publisher":"EMBO Press"},{"intvolume":" 31","month":"05","scopus_import":"1","oa_version":"Published Version","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"}],"volume":31,"issue":"7","language":[{"iso":"eng"}],"file":[{"content_type":"application/pdf","relation":"main_file","access_level":"open_access","checksum":"64d8f7467731ee5c166b10b939b8310b","file_id":"7892","file_size":4695682,"date_updated":"2020-07-14T12:48:04Z","creator":"dernst","file_name":"2020_CellReports_Parenti.pdf","date_created":"2020-05-26T11:05:01Z"}],"publication_status":"published","publication_identifier":{"eissn":["22111247"]},"status":"public","tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"article_type":"original","type":"journal_article","_id":"7877","department":[{"_id":"GaNo"}],"file_date_updated":"2020-07-14T12:48:04Z","ddc":["570"],"date_updated":"2023-08-21T06:27:47Z","oa":1,"quality_controlled":"1","publisher":"Elsevier","date_created":"2020-05-24T22:00:57Z","date_published":"2020-05-19T00:00:00Z","doi":"10.1016/j.celrep.2020.107647","publication":"Cell Reports","day":"19","year":"2020","isi":1,"has_accepted_license":"1","article_number":"107647","title":"MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader subunits and cause Cornelia de Lange syndrome","external_id":{"isi":["000535655200005"]},"article_processing_charge":"No","author":[{"full_name":"Parenti, Ilaria","last_name":"Parenti","first_name":"Ilaria","id":"D93538B0-5B71-11E9-AC62-02EBE5697425"},{"first_name":"Farah","last_name":"Diab","full_name":"Diab, Farah"},{"first_name":"Sara Ruiz","full_name":"Gil, Sara Ruiz","last_name":"Gil"},{"full_name":"Mulugeta, Eskeatnaf","last_name":"Mulugeta","first_name":"Eskeatnaf"},{"last_name":"Casa","full_name":"Casa, Valentina","first_name":"Valentina"},{"first_name":"Riccardo","full_name":"Berutti, Riccardo","last_name":"Berutti"},{"first_name":"Rutger W.W.","full_name":"Brouwer, Rutger W.W.","last_name":"Brouwer"},{"first_name":"Valerie","full_name":"Dupé, Valerie","last_name":"Dupé"},{"full_name":"Eckhold, Juliane","last_name":"Eckhold","first_name":"Juliane"},{"first_name":"Elisabeth","full_name":"Graf, Elisabeth","last_name":"Graf"},{"first_name":"Beatriz","full_name":"Puisac, Beatriz","last_name":"Puisac"},{"first_name":"Feliciano","last_name":"Ramos","full_name":"Ramos, Feliciano"},{"first_name":"Thomas","last_name":"Schwarzmayr","full_name":"Schwarzmayr, Thomas"},{"first_name":"Macarena Moronta","full_name":"Gines, Macarena Moronta","last_name":"Gines"},{"full_name":"Van Staveren, Thomas","last_name":"Van Staveren","first_name":"Thomas"},{"last_name":"Van Ijcken","full_name":"Van Ijcken, Wilfred F.J.","first_name":"Wilfred F.J."},{"full_name":"Strom, Tim M.","last_name":"Strom","first_name":"Tim M."},{"full_name":"Pié, Juan","last_name":"Pié","first_name":"Juan"},{"last_name":"Watrin","full_name":"Watrin, Erwan","first_name":"Erwan"},{"first_name":"Frank J.","full_name":"Kaiser, Frank J.","last_name":"Kaiser"},{"last_name":"Wendt","full_name":"Wendt, Kerstin S.","first_name":"Kerstin S."}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"ieee":"I. Parenti et al., “MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader subunits and cause Cornelia de Lange syndrome,” Cell Reports, vol. 31, no. 7. Elsevier, 2020.","short":"I. Parenti, F. Diab, S.R. Gil, E. Mulugeta, V. Casa, R. Berutti, R.W.W. Brouwer, V. Dupé, J. Eckhold, E. Graf, B. Puisac, F. Ramos, T. Schwarzmayr, M.M. Gines, T. Van Staveren, W.F.J. Van Ijcken, T.M. Strom, J. Pié, E. Watrin, F.J. Kaiser, K.S. Wendt, Cell Reports 31 (2020).","apa":"Parenti, I., Diab, F., Gil, S. R., Mulugeta, E., Casa, V., Berutti, R., … Wendt, K. S. (2020). MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader subunits and cause Cornelia de Lange syndrome. Cell Reports. Elsevier. https://doi.org/10.1016/j.celrep.2020.107647","ama":"Parenti I, Diab F, Gil SR, et al. MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader subunits and cause Cornelia de Lange syndrome. Cell Reports. 2020;31(7). doi:10.1016/j.celrep.2020.107647","mla":"Parenti, Ilaria, et al. “MAU2 and NIPBL Variants Impair the Heterodimerization of the Cohesin Loader Subunits and Cause Cornelia de Lange Syndrome.” Cell Reports, vol. 31, no. 7, 107647, Elsevier, 2020, doi:10.1016/j.celrep.2020.107647.","ista":"Parenti I, Diab F, Gil SR, Mulugeta E, Casa V, Berutti R, Brouwer RWW, Dupé V, Eckhold J, Graf E, Puisac B, Ramos F, Schwarzmayr T, Gines MM, Van Staveren T, Van Ijcken WFJ, Strom TM, Pié J, Watrin E, Kaiser FJ, Wendt KS. 2020. MAU2 and NIPBL variants impair the heterodimerization of the cohesin loader subunits and cause Cornelia de Lange syndrome. Cell Reports. 31(7), 107647.","chicago":"Parenti, Ilaria, Farah Diab, Sara Ruiz Gil, Eskeatnaf Mulugeta, Valentina Casa, Riccardo Berutti, Rutger W.W. Brouwer, et al. “MAU2 and NIPBL Variants Impair the Heterodimerization of the Cohesin Loader Subunits and Cause Cornelia de Lange Syndrome.” Cell Reports. Elsevier, 2020. https://doi.org/10.1016/j.celrep.2020.107647."}},{"date_created":"2020-06-14T22:00:49Z","doi":"10.1016/j.tins.2020.05.004","date_published":"2020-08-01T00:00:00Z","page":"608-621","publication":"Trends in Neurosciences","day":"01","year":"2020","isi":1,"has_accepted_license":"1","oa":1,"publisher":"Elsevier","quality_controlled":"1","acknowledgement":"We wish to thank Jasmin Morandell for generously sharing Figure 2. This work was supported by the European Research Council Starting Grant (grant 715508 ) to G.N.","title":"Neurodevelopmental disorders: From genetics to functional pathways","external_id":{"pmid":["32507511"],"isi":["000553090600008"]},"article_processing_charge":"No","author":[{"id":"D93538B0-5B71-11E9-AC62-02EBE5697425","first_name":"Ilaria","last_name":"Parenti","full_name":"Parenti, Ilaria"},{"first_name":"Luis E","id":"33D1B084-F248-11E8-B48F-1D18A9856A87","full_name":"Garcia Rabaneda, Luis E","last_name":"Garcia Rabaneda"},{"last_name":"Schön","full_name":"Schön, Hanna","id":"C8E17EDC-D7AA-11E9-B7B7-45ECE5697425","first_name":"Hanna"},{"last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"mla":"Parenti, Ilaria, et al. “Neurodevelopmental Disorders: From Genetics to Functional Pathways.” Trends in Neurosciences, vol. 43, no. 8, Elsevier, 2020, pp. 608–21, doi:10.1016/j.tins.2020.05.004.","short":"I. Parenti, L.E. Garcia Rabaneda, H. Schön, G. Novarino, Trends in Neurosciences 43 (2020) 608–621.","ieee":"I. Parenti, L. E. Garcia Rabaneda, H. Schön, and G. Novarino, “Neurodevelopmental disorders: From genetics to functional pathways,” Trends in Neurosciences, vol. 43, no. 8. Elsevier, pp. 608–621, 2020.","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","ama":"Parenti I, Garcia Rabaneda LE, Schön H, Novarino G. Neurodevelopmental disorders: From genetics to functional pathways. Trends in Neurosciences. 2020;43(8):608-621. doi:10.1016/j.tins.2020.05.004","chicago":"Parenti, Ilaria, Luis E Garcia Rabaneda, Hanna Schön, and Gaia Novarino. “Neurodevelopmental Disorders: From Genetics to Functional Pathways.” Trends in Neurosciences. Elsevier, 2020. https://doi.org/10.1016/j.tins.2020.05.004.","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."},"project":[{"_id":"25444568-B435-11E9-9278-68D0E5697425","call_identifier":"H2020","grant_number":"715508","name":"Probing the Reversibility of Autism Spectrum Disorders by Employing in vivo and in vitro Models"}],"ec_funded":1,"issue":"8","volume":43,"language":[{"iso":"eng"}],"file":[{"file_name":"2020_TrendsNeuroscience_Parenti.pdf","date_created":"2020-11-25T09:43:40Z","file_size":1439550,"date_updated":"2020-11-25T09:43:40Z","creator":"dernst","success":1,"checksum":"67db0251b1d415ae59005f876fcf9e34","file_id":"8805","content_type":"application/pdf","relation":"main_file","access_level":"open_access"}],"publication_status":"published","publication_identifier":{"eissn":["1878108X"],"issn":["01662236"]},"intvolume":" 43","month":"08","scopus_import":"1","oa_version":"Published Version","pmid":1,"abstract":[{"text":"Neurodevelopmental disorders (NDDs) are a class of disorders affecting brain development and function and are characterized by wide genetic and clinical variability. In this review, we discuss the multiple factors that influence the clinical presentation of NDDs, with particular attention to gene vulnerability, mutational load, and the two-hit model. Despite the complex architecture of\r\nmutational events associated with NDDs, the various proteins involved appear to converge on common pathways, such as synaptic plasticity/function, chromatin remodelers and the mammalian target of rapamycin (mTOR) pathway. A thorough understanding of the mechanisms behind these pathways will hopefully lead to the identification of candidates that could be targeted for treatment approaches.","lang":"eng"}],"department":[{"_id":"GaNo"}],"file_date_updated":"2020-11-25T09:43:40Z","ddc":["570"],"date_updated":"2023-08-21T08:25:31Z","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","article_type":"original","_id":"7957"},{"publisher":"Institute of Science and Technology Austria","oa":1,"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.","doi":"10.15479/AT:ISTA:8620","date_published":"2020-10-12T00:00:00Z","date_created":"2020-10-07T14:53:13Z","page":"138","day":"12","has_accepted_license":"1","year":"2020","project":[{"call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24","name":"Molecular Drug Targets"},{"name":"Neural stem cells in autism and epilepsy","grant_number":"F07807","_id":"05A0D778-7A3F-11EA-A408-12923DDC885E"}],"title":"Illuminating the role of Cul3 in autism spectrum disorder pathogenesis","author":[{"full_name":"Morandell, Jasmin","last_name":"Morandell","first_name":"Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87"}],"article_processing_charge":"No","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"ista":"Morandell J. 2020. Illuminating the role of Cul3 in autism spectrum disorder pathogenesis. Institute of Science and Technology Austria.","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.","ieee":"J. Morandell, “Illuminating the role of Cul3 in autism spectrum disorder pathogenesis,” Institute of Science and Technology Austria, 2020.","short":"J. Morandell, Illuminating the Role of Cul3 in Autism Spectrum Disorder Pathogenesis, Institute of Science and Technology Austria, 2020.","apa":"Morandell, J. (2020). Illuminating the role of Cul3 in autism spectrum disorder pathogenesis. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8620","ama":"Morandell J. Illuminating the role of Cul3 in autism spectrum disorder pathogenesis. 2020. doi:10.15479/AT:ISTA:8620","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."},"month":"10","alternative_title":["ISTA Thesis"],"oa_version":"Published Version","acknowledged_ssus":[{"_id":"Bio"},{"_id":"PreCl"}],"abstract":[{"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.","lang":"eng"}],"related_material":{"record":[{"id":"7800","status":"public","relation":"part_of_dissertation"},{"relation":"part_of_dissertation","status":"public","id":"8131"}]},"file":[{"embargo":"2021-10-15","checksum":"7ee83e42de3e5ce2fedb44dff472f75f","file_id":"8621","relation":"main_file","access_level":"open_access","content_type":"application/pdf","file_name":"Jasmin_Morandell_Thesis-2020_final.pdf","date_created":"2020-10-07T14:41:49Z","creator":"jmorande","file_size":16155786,"date_updated":"2021-10-16T22:30:04Z"},{"creator":"jmorande","date_updated":"2021-10-16T22:30:04Z","file_size":24344152,"date_created":"2020-10-07T14:45:07Z","file_name":"Jasmin_Morandell_Thesis-2020_final.zip","access_level":"closed","relation":"source_file","content_type":"application/x-zip-compressed","embargo_to":"open_access","file_id":"8622","checksum":"5e0464af453734210ce7aab7b4a92e3a"}],"language":[{"iso":"eng"}],"publication_identifier":{"issn":["2663-337X"]},"degree_awarded":"PhD","publication_status":"published","status":"public","type":"dissertation","_id":"8620","department":[{"_id":"GaNo"}],"file_date_updated":"2021-10-16T22:30:04Z","ddc":["610"],"supervisor":[{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"}],"date_updated":"2023-09-07T13:22:14Z"},{"date_updated":"2024-03-27T23:30:14Z","ddc":["570"],"file_date_updated":"2020-07-14T12:48:03Z","department":[{"_id":"JoDa"},{"_id":"GaNo"},{"_id":"LifeSc"}],"_id":"7800","type":"preprint","tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"status":"public","publication_status":"submitted","file":[{"content_type":"application/pdf","relation":"main_file","access_level":"open_access","checksum":"c6799ab5daba80efe8e2ed63c15f8c81","file_id":"7801","file_size":2931370,"date_updated":"2020-07-14T12:48:03Z","creator":"rsix","file_name":"2020.01.10.902064v1.full.pdf","date_created":"2020-05-05T14:31:19Z"}],"language":[{"iso":"eng"}],"related_material":{"record":[{"relation":"later_version","id":"9429","status":"public"},{"relation":"dissertation_contains","status":"public","id":"8620"}]},"acknowledged_ssus":[{"_id":"PreCl"}],"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"}],"oa_version":"Preprint","month":"01","citation":{"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 .","ama":"Morandell J, Schwarz LA, Basilico B, et al. Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. bioRxiv. doi:10.1101/2020.01.10.902064 ","apa":"Morandell, J., Schwarz, L. A., Basilico, B., Tasciyan, S., Nicolas, A., Sommer, C. M., … Novarino, G. (n.d.). Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.01.10.902064 ","ieee":"J. Morandell et al., “Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development,” bioRxiv. Cold Spring Harbor Laboratory.","short":"J. Morandell, L.A. Schwarz, B. Basilico, S. Tasciyan, A. Nicolas, C.M. Sommer, C. Kreuzinger, L. Knaus, Z. Dobler, E. Cacci, J.G. Danzl, G. Novarino, BioRxiv (n.d.).","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 .","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 ."},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","author":[{"last_name":"Morandell","full_name":"Morandell, Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","first_name":"Jasmin"},{"last_name":"Schwarz","full_name":"Schwarz, Lena A","id":"29A8453C-F248-11E8-B48F-1D18A9856A87","first_name":"Lena A"},{"full_name":"Basilico, Bernadette","orcid":"0000-0003-1843-3173","last_name":"Basilico","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","first_name":"Bernadette"},{"id":"4323B49C-F248-11E8-B48F-1D18A9856A87","first_name":"Saren","full_name":"Tasciyan, Saren","orcid":"0000-0003-1671-393X","last_name":"Tasciyan"},{"last_name":"Nicolas","full_name":"Nicolas, Armel","id":"2A103192-F248-11E8-B48F-1D18A9856A87","first_name":"Armel"},{"full_name":"Sommer, Christoph M","orcid":"0000-0003-1216-9105","last_name":"Sommer","first_name":"Christoph M","id":"4DF26D8C-F248-11E8-B48F-1D18A9856A87"},{"full_name":"Kreuzinger, Caroline","last_name":"Kreuzinger","id":"382077BA-F248-11E8-B48F-1D18A9856A87","first_name":"Caroline"},{"full_name":"Knaus, Lisa","last_name":"Knaus","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","first_name":"Lisa"},{"last_name":"Dobler","full_name":"Dobler, Zoe","id":"D23090A2-9057-11EA-883A-A8396FC7A38F","first_name":"Zoe"},{"first_name":"Emanuele","last_name":"Cacci","full_name":"Cacci, Emanuele"},{"first_name":"Johann G","id":"42EFD3B6-F248-11E8-B48F-1D18A9856A87","last_name":"Danzl","orcid":"0000-0001-8559-3973","full_name":"Danzl, Johann G"},{"last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"}],"article_processing_charge":"No","title":"Cul3 regulates cytoskeleton protein homeostasis and cell migration during a critical window of brain development","project":[{"name":"Optical control of synaptic function via adhesion molecules","grant_number":"I03600","call_identifier":"FWF","_id":"265CB4D0-B435-11E9-9278-68D0E5697425"},{"grant_number":"W1232-B24","name":"Molecular Drug Targets","call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425"}],"has_accepted_license":"1","year":"2020","day":"11","publication":"bioRxiv","doi":"10.1101/2020.01.10.902064 ","date_published":"2020-01-11T00:00:00Z","date_created":"2020-05-05T14:31:33Z","publisher":"Cold Spring Harbor Laboratory","oa":1},{"date_created":"2020-07-19T22:00:58Z","date_published":"2020-12-01T00:00:00Z","doi":"10.1016/j.gde.2020.06.004","page":"126-137","publication":"Current Opinion in Genetics and Development","day":"01","year":"2020","isi":1,"has_accepted_license":"1","oa":1,"publisher":"Elsevier","quality_controlled":"1","title":"Molecular mechanisms for targeted ASD treatments","external_id":{"pmid":["32659636"],"isi":["000598918900019"]},"article_processing_charge":"Yes (via OA deal)","author":[{"orcid":"0000-0003-1843-3173","full_name":"Basilico, Bernadette","last_name":"Basilico","id":"36035796-5ACA-11E9-A75E-7AF2E5697425","first_name":"Bernadette"},{"full_name":"Morandell, Jasmin","last_name":"Morandell","id":"4739D480-F248-11E8-B48F-1D18A9856A87","first_name":"Jasmin"},{"first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"}],"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","citation":{"chicago":"Basilico, Bernadette, Jasmin Morandell, and Gaia Novarino. “Molecular Mechanisms for Targeted ASD Treatments.” Current Opinion in Genetics and Development. Elsevier, 2020. https://doi.org/10.1016/j.gde.2020.06.004.","ista":"Basilico B, Morandell J, Novarino G. 2020. Molecular mechanisms for targeted ASD treatments. Current Opinion in Genetics and Development. 65(12), 126–137.","mla":"Basilico, Bernadette, et al. “Molecular Mechanisms for Targeted ASD Treatments.” Current Opinion in Genetics and Development, vol. 65, no. 12, Elsevier, 2020, pp. 126–37, doi:10.1016/j.gde.2020.06.004.","apa":"Basilico, B., Morandell, J., & Novarino, G. (2020). Molecular mechanisms for targeted ASD treatments. Current Opinion in Genetics and Development. Elsevier. https://doi.org/10.1016/j.gde.2020.06.004","ama":"Basilico B, Morandell J, Novarino G. Molecular mechanisms for targeted ASD treatments. Current Opinion in Genetics and Development. 2020;65(12):126-137. doi:10.1016/j.gde.2020.06.004","ieee":"B. Basilico, J. Morandell, and G. Novarino, “Molecular mechanisms for targeted ASD treatments,” Current Opinion in Genetics and Development, vol. 65, no. 12. Elsevier, pp. 126–137, 2020.","short":"B. Basilico, J. Morandell, G. Novarino, Current Opinion in Genetics and Development 65 (2020) 126–137."},"project":[{"grant_number":"754411","name":"ISTplus - Postdoctoral Fellowships","call_identifier":"H2020","_id":"260C2330-B435-11E9-9278-68D0E5697425"},{"call_identifier":"FWF","_id":"2548AE96-B435-11E9-9278-68D0E5697425","grant_number":"W1232-B24","name":"Molecular Drug Targets"},{"_id":"05A0D778-7A3F-11EA-A408-12923DDC885E","name":"Neural stem cells in autism and epilepsy","grant_number":"F07807"}],"ec_funded":1,"volume":65,"issue":"12","related_material":{"record":[{"status":"public","id":"8620","relation":"dissertation_contains"}]},"language":[{"iso":"eng"}],"file":[{"success":1,"file_id":"8146","content_type":"application/pdf","relation":"main_file","access_level":"open_access","file_name":"2020_CurrentOpGenetics_Basilico.pdf","date_created":"2020-07-22T06:47:45Z","file_size":1381545,"date_updated":"2020-07-22T06:47:45Z","creator":"dernst"}],"publication_status":"published","publication_identifier":{"issn":["0959437X"],"eissn":["18790380"]},"intvolume":" 65","month":"12","scopus_import":"1","oa_version":"Published Version","pmid":1,"abstract":[{"lang":"eng","text":"The possibility to generate construct valid animal models enabled the development and testing of therapeutic strategies targeting the core features of autism spectrum disorders (ASDs). At the same time, these studies highlighted the necessity of identifying sensitive developmental time windows for successful therapeutic interventions. Animal and human studies also uncovered the possibility to stratify the variety of ASDs in molecularly distinct subgroups, potentially facilitating effective treatment design. Here, we focus on the molecular pathways emerging as commonly affected by mutations in diverse ASD-risk genes, on their role during critical windows of brain development and the potential treatments targeting these biological processes."}],"department":[{"_id":"GaNo"}],"file_date_updated":"2020-07-22T06:47:45Z","ddc":["570"],"date_updated":"2024-03-27T23:30:14Z","status":"public","tmp":{"short":"CC BY-NC-ND (4.0)","name":"Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)","legal_code_url":"https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode","image":"/images/cc_by_nc_nd.png"},"type":"journal_article","article_type":"original","_id":"8131"},{"abstract":[{"text":"Clinical Utility Gene Card. 1. Name of Disease (Synonyms): Pontocerebellar hypoplasia type 9 (PCH9) and spastic paraplegia-63 (SPG63). 2. OMIM# of the Disease: 615809 and 615686. 3. Name of the Analysed Genes or DNA/Chromosome Segments: AMPD2 at 1p13.3. 4. OMIM# of the Gene(s): 102771.","lang":"eng"}],"oa_version":"Published Version","pmid":1,"main_file_link":[{"open_access":"1","url":"https://doi.org/10.1038/s41431-018-0231-2"}],"scopus_import":"1","intvolume":" 27","month":"01","publication_status":"published","language":[{"iso":"eng"}],"volume":27,"_id":"105","article_type":"original","type":"journal_article","status":"public","date_updated":"2023-08-24T14:28:24Z","department":[{"_id":"GaNo"}],"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.","oa":1,"publisher":"Springer Nature","quality_controlled":"1","year":"2019","isi":1,"publication":"European Journal of Human Genetics","day":"01","page":"161-166","date_created":"2018-12-11T11:44:39Z","date_published":"2019-01-01T00:00:00Z","doi":"10.1038/s41431-018-0231-2","citation":{"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.","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.","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","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","short":"A. Marsh, G. Novarino, P. Lockhart, R. Leventer, European Journal of Human Genetics 27 (2019) 161–166.","ieee":"A. Marsh, G. Novarino, P. Lockhart, and R. Leventer, “CUGC for pontocerebellar hypoplasia type 9 and spastic paraplegia-63,” European Journal of Human Genetics, vol. 27. Springer Nature, pp. 161–166, 2019.","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."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","article_processing_charge":"No","external_id":{"pmid":["30089829"],"isi":["000454111500019"]},"publist_id":"7949","author":[{"first_name":"Ashley","full_name":"Marsh, Ashley","last_name":"Marsh"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","last_name":"Novarino","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia"},{"last_name":"Lockhart","full_name":"Lockhart, Paul","first_name":"Paul"},{"first_name":"Richard","full_name":"Leventer, Richard","last_name":"Leventer"}],"title":"CUGC for pontocerebellar hypoplasia type 9 and spastic paraplegia-63"},{"type":"journal_article","status":"public","_id":"6088","department":[{"_id":"GaNo"}],"date_updated":"2023-08-25T08:02:51Z","scopus_import":"1","intvolume":" 16","month":"03","abstract":[{"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.","lang":"eng"}],"oa_version":"None","pmid":1,"volume":16,"issue":"3","publication_status":"published","language":[{"iso":"eng"}],"article_processing_charge":"No","external_id":{"pmid":["30694684"],"isi":["000460600400031"]},"author":[{"first_name":"Alexander","last_name":"Traxl","full_name":"Traxl, Alexander"},{"first_name":"Severin","full_name":"Mairinger, Severin","last_name":"Mairinger"},{"full_name":"Filip, Thomas","last_name":"Filip","first_name":"Thomas"},{"full_name":"Sauberer, Michael","last_name":"Sauberer","first_name":"Michael"},{"first_name":"Johann","last_name":"Stanek","full_name":"Stanek, Johann"},{"last_name":"Poschner","full_name":"Poschner, Stefan","first_name":"Stefan"},{"first_name":"Walter","full_name":"Jäger, Walter","last_name":"Jäger"},{"first_name":"Viktoria","last_name":"Zoufal","full_name":"Zoufal, Viktoria"},{"orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia"},{"full_name":"Tournier, Nicolas","last_name":"Tournier","first_name":"Nicolas"},{"full_name":"Bauer, Martin","last_name":"Bauer","first_name":"Martin"},{"full_name":"Wanek, Thomas","last_name":"Wanek","first_name":"Thomas"},{"full_name":"Langer, Oliver","last_name":"Langer","first_name":"Oliver"}],"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","citation":{"ieee":"A. Traxl et al., “Inhibition of ABCB1 and ABCG2 at the mouse blood-brain barrier with marketed drugs to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib,” Molecular Pharmaceutics, vol. 16, no. 3. American Chemical Society, pp. 1282–1293, 2019.","short":"A. Traxl, S. Mairinger, T. Filip, M. Sauberer, J. Stanek, S. Poschner, W. Jäger, V. Zoufal, G. Novarino, N. Tournier, M. Bauer, T. Wanek, O. Langer, Molecular Pharmaceutics 16 (2019) 1282–1293.","apa":"Traxl, A., Mairinger, S., Filip, T., Sauberer, M., Stanek, J., Poschner, S., … Langer, O. (2019). Inhibition of ABCB1 and ABCG2 at the mouse blood-brain barrier with marketed drugs to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib. Molecular Pharmaceutics. American Chemical Society. https://doi.org/10.1021/acs.molpharmaceut.8b01217","ama":"Traxl A, Mairinger S, Filip T, et al. Inhibition of ABCB1 and ABCG2 at the mouse blood-brain barrier with marketed drugs to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib. Molecular Pharmaceutics. 2019;16(3):1282-1293. doi:10.1021/acs.molpharmaceut.8b01217","mla":"Traxl, Alexander, et al. “Inhibition of ABCB1 and ABCG2 at the Mouse Blood-Brain Barrier with Marketed Drugs to Improve Brain Delivery of the Model ABCB1/ABCG2 Substrate [11C]Erlotinib.” Molecular Pharmaceutics, vol. 16, no. 3, American Chemical Society, 2019, pp. 1282–93, doi:10.1021/acs.molpharmaceut.8b01217.","ista":"Traxl A, Mairinger S, Filip T, Sauberer M, Stanek J, Poschner S, Jäger W, Zoufal V, Novarino G, Tournier N, Bauer M, Wanek T, Langer O. 2019. Inhibition of ABCB1 and ABCG2 at the mouse blood-brain barrier with marketed drugs to improve brain delivery of the model ABCB1/ABCG2 substrate [11C]erlotinib. Molecular Pharmaceutics. 16(3), 1282–1293.","chicago":"Traxl, Alexander, Severin Mairinger, Thomas Filip, Michael Sauberer, Johann Stanek, Stefan Poschner, Walter Jäger, et al. “Inhibition of ABCB1 and ABCG2 at the Mouse Blood-Brain Barrier with Marketed Drugs to Improve Brain Delivery of the Model ABCB1/ABCG2 Substrate [11C]Erlotinib.” Molecular Pharmaceutics. American Chemical Society, 2019. https://doi.org/10.1021/acs.molpharmaceut.8b01217."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","quality_controlled":"1","publisher":"American Chemical Society","page":"1282-1293","date_created":"2019-03-10T22:59:19Z","date_published":"2019-03-04T00:00:00Z","doi":"10.1021/acs.molpharmaceut.8b01217","year":"2019","isi":1,"publication":"Molecular Pharmaceutics","day":"04"},{"quality_controlled":"1","publisher":"Wiley","oa":1,"isi":1,"year":"2019","day":"01","publication":"Journal of Physiology","page":"2925–2947","date_published":"2019-06-01T00:00:00Z","doi":"10.1113/JP277681","date_created":"2019-05-19T21:59:17Z","citation":{"apa":"Éltes, T., Szoboszlay, M., Szigeti, M. K., & Nusser, Z. (2019). Improved spike inference accuracy by estimating the peak amplitude of unitary [Ca2+] transients in weakly GCaMP6f-expressing hippocampal pyramidal cells. Journal of Physiology. Wiley. https://doi.org/10.1113/JP277681","ama":"Éltes T, Szoboszlay M, Szigeti MK, Nusser Z. Improved spike inference accuracy by estimating the peak amplitude of unitary [Ca2+] transients in weakly GCaMP6f-expressing hippocampal pyramidal cells. Journal of Physiology. 2019;597(11):2925–2947. doi:10.1113/JP277681","ieee":"T. Éltes, M. Szoboszlay, M. K. Szigeti, and Z. Nusser, “Improved spike inference accuracy by estimating the peak amplitude of unitary [Ca2+] transients in weakly GCaMP6f-expressing hippocampal pyramidal cells,” Journal of Physiology, vol. 597, no. 11. Wiley, pp. 2925–2947, 2019.","short":"T. Éltes, M. Szoboszlay, M.K. Szigeti, Z. Nusser, Journal of Physiology 597 (2019) 2925–2947.","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.","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.","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."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","author":[{"full_name":"Éltes, Tímea","last_name":"Éltes","first_name":"Tímea"},{"full_name":"Szoboszlay, Miklos","last_name":"Szoboszlay","first_name":"Miklos"},{"orcid":"0000-0001-9500-8758","full_name":"Szigeti, Margit Katalin","last_name":"Szigeti","first_name":"Margit Katalin","id":"44F4BDC0-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Zoltan","last_name":"Nusser","full_name":"Nusser, Zoltan"}],"article_processing_charge":"No","external_id":{"isi":["000470780400013"],"pmid":["31006863"]},"title":"Improved spike inference accuracy by estimating the peak amplitude of unitary [Ca2+] transients in weakly GCaMP6f-expressing hippocampal pyramidal cells","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"}],"pmid":1,"oa_version":"Published Version","scopus_import":"1","main_file_link":[{"open_access":"1","url":"https://doi.org/10.1113/JP277681"}],"month":"06","intvolume":" 597","publication_identifier":{"eissn":["14697793"],"issn":["00223751"]},"publication_status":"published","language":[{"iso":"eng"}],"volume":597,"issue":"11","_id":"6470","type":"journal_article","article_type":"original","status":"public","date_updated":"2023-08-25T10:34:15Z","department":[{"_id":"GaNo"}]},{"citation":{"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","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","ieee":"B. Oliveira, A. Ç. Yahya, and G. Novarino, “Modeling cell-cell interactions in the brain using cerebral organoids,” Brain Research, vol. 1724. Elsevier, 2019.","short":"B. Oliveira, A.Ç. Yahya, G. Novarino, Brain Research 1724 (2019).","mla":"Oliveira, Bárbara, et al. “Modeling Cell-Cell Interactions in the Brain Using Cerebral Organoids.” Brain Research, vol. 1724, 146458, Elsevier, 2019, doi:10.1016/j.brainres.2019.146458.","ista":"Oliveira B, Yahya AÇ, Novarino G. 2019. Modeling cell-cell interactions in the brain using cerebral organoids. Brain Research. 1724, 146458.","chicago":"Oliveira, Bárbara, Aysan Çerağ Yahya, and Gaia Novarino. “Modeling Cell-Cell Interactions in the Brain Using Cerebral Organoids.” Brain Research. Elsevier, 2019. https://doi.org/10.1016/j.brainres.2019.146458."},"user_id":"4359f0d1-fa6c-11eb-b949-802e58b17ae8","external_id":{"pmid":["31521639"],"isi":["000491646600033"]},"article_processing_charge":"No","author":[{"last_name":"Oliveira","full_name":"Oliveira, Bárbara","id":"3B03AA1A-F248-11E8-B48F-1D18A9856A87","first_name":"Bárbara"},{"full_name":"Yahya, Aysan Çerağ","last_name":"Yahya","first_name":"Aysan Çerağ","id":"365A65F8-F248-11E8-B48F-1D18A9856A87"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178"}],"title":"Modeling cell-cell interactions in the brain using cerebral organoids","article_number":"146458","year":"2019","isi":1,"publication":"Brain Research","day":"01","date_created":"2019-09-22T22:00:35Z","date_published":"2019-12-01T00:00:00Z","doi":"10.1016/j.brainres.2019.146458","publisher":"Elsevier","quality_controlled":"1","date_updated":"2023-08-30T06:19:49Z","department":[{"_id":"GaNo"}],"_id":"6896","type":"journal_article","article_type":"original","status":"public","publication_status":"published","publication_identifier":{"eissn":["18726240"],"issn":["00068993"]},"language":[{"iso":"eng"}],"volume":1724,"abstract":[{"text":"Until recently, a great amount of brain studies have been conducted in human post mortem tissues, cell lines and model organisms. These researches provided useful insights regarding cell-cell interactions occurring in the brain. However, such approaches suffer from technical limitations and inaccurate modeling of the tissue 3D cytoarchitecture. Importantly, they might lack a human genetic background essential for disease modeling. With the development of protocols to generate human cerebral organoids, we are now closer to reproducing the early stages of human brain development in vitro. As a result, more relevant cell-cell interaction studies can be conducted.\r\n\r\nIn this review, we discuss the advantages of 3D cultures over 2D in modulating brain cell-cell interactions during physiological and pathological development, as well as the progress made in developing organoids in which neurons, macroglia, microglia and vascularization are present. Finally, we debate the limitations of those models and possible future directions.","lang":"eng"}],"oa_version":"None","pmid":1,"scopus_import":"1","intvolume":" 1724","month":"12"},{"_id":"7415","status":"public","article_type":"original","type":"journal_article","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","date_updated":"2023-09-07T14:56:17Z","citation":{"mla":"Morandell, Jasmin, et al. “S.16.05 Illuminating the Role of the E3 Ubiquitin Ligase Cullin3 in Brain Development and Autism.” European Neuropsychopharmacology, vol. 29, no. Supplement 6, Elsevier, 2019, pp. S11–12, doi:10.1016/j.euroneuro.2019.09.040.","ieee":"J. Morandell, A. Nicolas, L. A. Schwarz, and G. Novarino, “S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism,” European Neuropsychopharmacology, vol. 29, no. Supplement 6. Elsevier, pp. S11–S12, 2019.","short":"J. Morandell, A. Nicolas, L.A. Schwarz, G. Novarino, European Neuropsychopharmacology 29 (2019) S11–S12.","ama":"Morandell J, Nicolas A, Schwarz LA, Novarino G. S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism. European Neuropsychopharmacology. 2019;29(Supplement 6):S11-S12. doi:10.1016/j.euroneuro.2019.09.040","apa":"Morandell, J., Nicolas, A., Schwarz, L. A., & Novarino, G. (2019). S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism. European Neuropsychopharmacology. Elsevier. https://doi.org/10.1016/j.euroneuro.2019.09.040","chicago":"Morandell, Jasmin, Armel Nicolas, Lena A Schwarz, and Gaia Novarino. “S.16.05 Illuminating the Role of the E3 Ubiquitin Ligase Cullin3 in Brain Development and Autism.” European Neuropsychopharmacology. Elsevier, 2019. https://doi.org/10.1016/j.euroneuro.2019.09.040.","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."},"department":[{"_id":"GaNo"},{"_id":"LifeSc"}],"title":"S.16.05 Illuminating the role of the e3 ubiquitin ligase cullin3 in brain development and autism","external_id":{"isi":["000502657500021"]},"article_processing_charge":"No","author":[{"first_name":"Jasmin","id":"4739D480-F248-11E8-B48F-1D18A9856A87","last_name":"Morandell","full_name":"Morandell, Jasmin"},{"full_name":"Nicolas, Armel","last_name":"Nicolas","id":"2A103192-F248-11E8-B48F-1D18A9856A87","first_name":"Armel"},{"id":"29A8453C-F248-11E8-B48F-1D18A9856A87","first_name":"Lena A","last_name":"Schwarz","full_name":"Schwarz, Lena A"},{"first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","last_name":"Novarino"}],"oa_version":"None","intvolume":" 29","month":"12","quality_controlled":"1","publisher":"Elsevier","publication":"European Neuropsychopharmacology","language":[{"iso":"eng"}],"day":"13","year":"2019","publication_status":"published","publication_identifier":{"issn":["0924-977X"]},"isi":1,"date_created":"2020-01-30T10:07:41Z","issue":"Supplement 6","volume":29,"doi":"10.1016/j.euroneuro.2019.09.040","date_published":"2019-12-13T00:00:00Z","page":"S11-S12"},{"language":[{"iso":"eng"}],"publication":"European Neuropsychopharmacology","day":"13","year":"2019","publication_status":"published","isi":1,"publication_identifier":{"issn":["0924-977X"]},"date_created":"2020-01-30T10:06:15Z","doi":"10.1016/j.euroneuro.2019.09.039","issue":"Supplement 6","date_published":"2019-12-13T00:00:00Z","volume":29,"page":"S11","oa_version":"None","intvolume":" 29","month":"12","publisher":"Elsevier","quality_controlled":"1","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","date_updated":"2023-09-07T14:55:23Z","citation":{"apa":"Knaus, L., Tarlungeanu, D.-C., & Novarino, G. (2019). S.16.03 A homozygous missense mutation in SLC7A5 leads to autism spectrum disorder and microcephaly. European Neuropsychopharmacology. Elsevier. https://doi.org/10.1016/j.euroneuro.2019.09.039","ama":"Knaus L, Tarlungeanu D-C, Novarino G. S.16.03 A homozygous missense mutation in SLC7A5 leads to autism spectrum disorder and microcephaly. European Neuropsychopharmacology. 2019;29(Supplement 6):S11. doi:10.1016/j.euroneuro.2019.09.039","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.","short":"L. Knaus, D.-C. Tarlungeanu, G. Novarino, European Neuropsychopharmacology 29 (2019) S11.","mla":"Knaus, Lisa, et al. “S.16.03 A Homozygous Missense Mutation in SLC7A5 Leads to Autism Spectrum Disorder and Microcephaly.” European Neuropsychopharmacology, vol. 29, no. Supplement 6, Elsevier, 2019, p. S11, doi:10.1016/j.euroneuro.2019.09.039.","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.","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."},"title":"S.16.03 A homozygous missense mutation in SLC7A5 leads to autism spectrum disorder and microcephaly","department":[{"_id":"GaNo"}],"article_processing_charge":"No","external_id":{"isi":["000502657500020"]},"author":[{"first_name":"Lisa","id":"3B2ABCF4-F248-11E8-B48F-1D18A9856A87","full_name":"Knaus, Lisa","last_name":"Knaus"},{"first_name":"Dora-Clara","id":"2ABCE612-F248-11E8-B48F-1D18A9856A87","full_name":"Tarlungeanu, Dora-Clara","last_name":"Tarlungeanu"},{"first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178"}],"_id":"7414","status":"public","type":"journal_article","article_type":"original"},{"month":"01","oa":1,"publisher":"Institute of Science and Technology Austria","oa_version":"Published Version","abstract":[{"lang":"eng","text":"This dataset contains the supplementary data for the research paper \"Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition\".\r\n\r\nThe contained files have the following content:\r\n'Supplementary Figures.pdf'\r\n\tAdditional figures (as referenced in the paper).\r\n'Supplementary Table 1. Statistics.xlsx'\r\n\tDetails on statistical tests performed in the paper.\r\n'Supplementary Table 2. Differentially expressed gene analysis.xlsx'\r\n\tResults for the differential gene expression analysis for embryonic (E9.5; analysis with edgeR) and in vitro (ESCs, EBs, NPCs; analysis with DESeq2) samples.\r\n'Supplementary Table 3. Gene Ontology (GO) term enrichment analysis.xlsx'\r\n\tResults for the GO term enrichment analysis for differentially expressed genes in embryonic (GO E9.5) and in vitro (GO ESC, GO EBs, GO NPCs) samples. Differentially expressed genes for in vitro samples were split into upregulated and downregulated genes (up/down) and the analysis was performed on each subset (e.g. GO ESC up / GO ESC down).\r\n'Supplementary Table 4. Differentially expressed gene analysis for CFC samples.xlsx'\r\n\tResults for the differential gene expression analysis for samples from adult mice before (HC - Homecage) and 1h and 3h after contextual fear conditioning (1h and 3h, respectively). Each sheet shows the results for a different comparison. Sheets 1-3 show results for comparisons between timepoints for wild type (WT) samples only and sheets 4-6 for the same comparisons in mutant (Het) samples. Sheets 7-9 show results for comparisons between genotypes at each time point and sheet 10 contains the results for the analysis of differential expression trajectories between wild type and mutant.\r\n'Supplementary Table 5. Cluster identification.xlsx'\r\n\tResults for k-means clustering of genes by expression. Sheet 1 shows clustering of just the genes with significantly different expression trajectories between genotypes. Sheet 2 shows clustering of all genes that are significantly differentially expressed in any of the comparisons (includes also genes with same trajectories).\r\n'Supplementary Table 6. GO term cluster analysis.xlsx'\r\n\tResults for the GO term enrichment analysis and EWCE analysis for enrichment of cell type specific genes for each cluster identified by clustering genes with different expression trajectories (see Table S5, sheet 1).\r\n'Supplementary Table 7. Setd5 mass spectrometry results.xlsx'\r\n\tResults showing proteins interacting with Setd5 as identified by mass spectrometry. Sheet 1 shows protein protein interaction data generated from these results (combined with data from the STRING database. Sheet 2 shows the results of the statistical analysis with limma.\r\n'Supplementary Table 8. PolII ChIP-seq analysis.xlsx'\r\n\tResults for the Chip-Seq analysis for binding of RNA polymerase II (PolII). Sheet 1 shows results for differential binding of PolII at the transcription start site (TSS) between genotypes and sheets 2+3 show the corresponding GO enrichment analysis for these differentially bound genes. Sheet 4 shows RNAseq counts for genes with increased binding of PolII at the TSS."}],"date_created":"2019-03-07T13:32:35Z","related_material":{"record":[{"status":"public","id":"3","relation":"research_paper"}]},"doi":"10.15479/AT:ISTA:6074","date_published":"2019-01-09T00:00:00Z","file":[{"date_created":"2019-03-07T13:37:19Z","file_name":"Setd5_paper.zip","date_updated":"2020-07-14T12:47:18Z","file_size":33202743,"creator":"dernst","file_id":"6084","checksum":"bc1b285edca9e98a2c63d153c79bb75b","content_type":"application/zip","access_level":"open_access","relation":"supplementary_material"}],"day":"09","year":"2019","has_accepted_license":"1","status":"public","type":"research_data","_id":"6074","department":[{"_id":"GaNo"}],"title":"Supplementary data for the research paper \"Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition\"","file_date_updated":"2020-07-14T12:47:18Z","article_processing_charge":"No","author":[{"full_name":"Dotter, Christoph","orcid":"0000-0002-9033-9096","last_name":"Dotter","first_name":"Christoph","id":"4C66542E-F248-11E8-B48F-1D18A9856A87"},{"first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178"}],"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","ddc":["570"],"citation":{"mla":"Dotter, Christoph, and Gaia Novarino. Supplementary Data for the Research Paper “Haploinsufficiency of the Intellectual Disability Gene SETD5 Disturbs Developmental Gene Expression and Cognition.” Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6074.","ieee":"C. Dotter and G. Novarino, “Supplementary data for the research paper ‘Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition.’” Institute of Science and Technology Austria, 2019.","short":"C. Dotter, G. Novarino, (2019).","ama":"Dotter C, Novarino G. Supplementary data for the research paper “Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition.” 2019. doi:10.15479/AT:ISTA:6074","apa":"Dotter, C., & Novarino, G. (2019). Supplementary data for the research paper “Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition.” Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6074","chicago":"Dotter, Christoph, and Gaia Novarino. “Supplementary Data for the Research Paper ‘Haploinsufficiency of the Intellectual Disability Gene SETD5 Disturbs Developmental Gene Expression and Cognition.’” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6074.","ista":"Dotter C, Novarino G. 2019. Supplementary data for the research paper ‘Haploinsufficiency of the intellectual disability gene SETD5 disturbs developmental gene expression and cognition’, Institute of Science and Technology Austria, 10.15479/AT:ISTA:6074."},"date_updated":"2024-02-21T13:41:01Z"},{"user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","date_updated":"2021-01-12T07:59:42Z","citation":{"chicago":"Novarino, Gaia. “Zika-Associated Microcephaly: Reduce the Stress and Race for the Treatment.” Science Translational Medicine. American Association for the Advancement of Science, 2018. https://doi.org/10.1126/scitranslmed.aar7514.","ista":"Novarino G. 2018. Zika-associated microcephaly: Reduce the stress and race for the treatment. Science Translational Medicine. 10(423), eaar7514.","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.","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","short":"G. Novarino, Science Translational Medicine 10 (2018).","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."},"title":"Zika-associated microcephaly: Reduce the stress and race for the treatment","department":[{"_id":"GaNo"}],"author":[{"first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","last_name":"Novarino"}],"publist_id":"7365","article_number":"eaar7514","_id":"456","status":"public","type":"journal_article","day":"10","publication":"Science Translational Medicine","language":[{"iso":"eng"}],"year":"2018","publication_status":"published","date_published":"2018-01-10T00:00:00Z","volume":10,"doi":"10.1126/scitranslmed.aar7514","issue":"423","date_created":"2018-12-11T11:46:34Z","oa_version":"None","abstract":[{"text":"Inhibition of the endoplasmic reticulum stress pathway may hold the key to Zika virus-associated microcephaly treatment. ","lang":"eng"}],"month":"01","intvolume":" 10","scopus_import":1,"publisher":"American Association for the Advancement of Science","quality_controlled":"1"},{"_id":"5888","status":"public","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"type":"journal_article","ddc":["570"],"date_updated":"2023-09-11T14:04:41Z","file_date_updated":"2020-07-14T12:47:13Z","department":[{"_id":"GaNo"}],"pmid":1,"oa_version":"Published Version","abstract":[{"lang":"eng","text":"Despite the remarkable number of scientific breakthroughs of the last 100 years, the treatment of neurodevelopmental\r\ndisorders (e.g., autism spectrum disorder, intellectual disability) remains a great challenge. Recent advancements in\r\ngenomics, such as whole-exome or whole-genome sequencing, have enabled scientists to identify numerous\r\nmutations underlying neurodevelopmental disorders. Given the few hundred risk genes that have been discovered,\r\nthe etiological variability and the heterogeneous clinical presentation, the need for genotype — along with phenotype-\r\nbased diagnosis of individual patients has become a requisite. In this review we look at recent advancements in\r\ngenomic analysis and their translation into clinical practice."}],"intvolume":" 50","month":"08","scopus_import":"1","language":[{"iso":"eng"}],"file":[{"content_type":"application/pdf","access_level":"open_access","relation":"main_file","file_id":"5893","checksum":"4498301c8c53097c9a1a8ef990936eb5","date_updated":"2020-07-14T12:47:13Z","file_size":1237482,"creator":"dernst","date_created":"2019-01-28T15:18:02Z","file_name":"2018_EMM_Tarlungeanu.pdf"}],"publication_status":"published","publication_identifier":{"issn":["2092-6413"]},"issue":"8","volume":50,"article_number":"100","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"chicago":"Tarlungeanu, Dora-Clara, and Gaia Novarino. “Genomics in Neurodevelopmental Disorders: An Avenue to Personalized Medicine.” Experimental & Molecular Medicine. Springer Nature, 2018. https://doi.org/10.1038/s12276-018-0129-7.","ista":"Tarlungeanu D-C, Novarino G. 2018. Genomics in neurodevelopmental disorders: an avenue to personalized medicine. Experimental & Molecular Medicine. 50(8), 100.","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.","apa":"Tarlungeanu, D.-C., & Novarino, G. (2018). Genomics in neurodevelopmental disorders: an avenue to personalized medicine. Experimental & Molecular Medicine. Springer Nature. https://doi.org/10.1038/s12276-018-0129-7","ama":"Tarlungeanu D-C, Novarino G. Genomics in neurodevelopmental disorders: an avenue to personalized medicine. Experimental & Molecular Medicine. 2018;50(8). doi:10.1038/s12276-018-0129-7","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.","short":"D.-C. Tarlungeanu, G. Novarino, Experimental & Molecular Medicine 50 (2018)."},"title":"Genomics in neurodevelopmental disorders: an avenue to personalized medicine","external_id":{"pmid":["30089840"],"isi":["000441266700006"]},"article_processing_charge":"No","author":[{"last_name":"Tarlungeanu","full_name":"Tarlungeanu, Dora-Clara","id":"2ABCE612-F248-11E8-B48F-1D18A9856A87","first_name":"Dora-Clara"},{"first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","last_name":"Novarino"}],"oa":1,"publisher":"Springer Nature","quality_controlled":"1","publication":"Experimental & Molecular Medicine","day":"07","year":"2018","isi":1,"has_accepted_license":"1","date_created":"2019-01-27T22:59:11Z","doi":"10.1038/s12276-018-0129-7","date_published":"2018-08-07T00:00:00Z"},{"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."}],"oa_version":"None","scopus_import":"1","month":"02","intvolume":" 48","publication_status":"published","language":[{"iso":"eng"}],"issue":"2","volume":48,"_id":"546","type":"journal_article","status":"public","date_updated":"2023-09-13T09:01:56Z","department":[{"_id":"GaNo"}],"publisher":"Elsevier","quality_controlled":"1","isi":1,"year":"2018","day":"01","publication":"Current Opinion in Neurobiology","page":"131 - 138","date_published":"2018-02-01T00:00:00Z","doi":"10.1016/j.conb.2017.12.005","date_created":"2018-12-11T11:47:06Z","citation":{"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.","ista":"Sacco R, Cacci E, Novarino G. 2018. Neural stem cells in neuropsychiatric disorders. Current Opinion in Neurobiology. 48(2), 131–138.","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.","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","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.","short":"R. Sacco, E. Cacci, G. Novarino, Current Opinion in Neurobiology 48 (2018) 131–138."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","publist_id":"7268","author":[{"id":"42C9F57E-F248-11E8-B48F-1D18A9856A87","first_name":"Roberto","full_name":"Sacco, Roberto","last_name":"Sacco"},{"last_name":"Cacci","full_name":"Cacci, Emanuele","first_name":"Emanuele"},{"last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87"}],"external_id":{"isi":["000427101600018"]},"article_processing_charge":"No","title":"Neural stem cells in neuropsychiatric disorders"}]