[{"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","title":"Zika-associated microcephaly: Reduce the stress and race for the treatment","department":[{"_id":"GaNo"}],"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","ieee":"G. Novarino, “Zika-associated microcephaly: Reduce the stress and race for the treatment,” Science Translational Medicine, vol. 10, no. 423. American Association for the Advancement of Science, 2018.","short":"G. Novarino, Science Translational Medicine 10 (2018)."},"user_id":"4435EBFC-F248-11E8-B48F-1D18A9856A87","type":"journal_article","status":"public","_id":"456","article_number":"eaar7514","volume":10,"issue":"423","date_published":"2018-01-10T00:00:00Z","doi":"10.1126/scitranslmed.aar7514","date_created":"2018-12-11T11:46:34Z","year":"2018","publication_status":"published","day":"10","publication":"Science Translational Medicine","language":[{"iso":"eng"}],"scopus_import":1,"quality_controlled":"1","publisher":"American Association for the Advancement of Science","month":"01","intvolume":" 10","abstract":[{"text":"Inhibition of the endoplasmic reticulum stress pathway may hold the key to Zika virus-associated microcephaly treatment. ","lang":"eng"}],"oa_version":"None"},{"article_number":"100","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.","ama":"Tarlungeanu D-C, Novarino G. Genomics in neurodevelopmental disorders: an avenue to personalized medicine. Experimental & Molecular Medicine. 2018;50(8). doi:10.1038/s12276-018-0129-7","apa":"Tarlungeanu, D.-C., & Novarino, G. (2018). Genomics in neurodevelopmental disorders: an avenue to personalized medicine. Experimental & Molecular Medicine. Springer Nature. https://doi.org/10.1038/s12276-018-0129-7","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)."},"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","author":[{"last_name":"Tarlungeanu","full_name":"Tarlungeanu, Dora-Clara","id":"2ABCE612-F248-11E8-B48F-1D18A9856A87","first_name":"Dora-Clara"},{"orcid":"0000-0002-7673-7178","full_name":"Novarino, Gaia","last_name":"Novarino","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia"}],"article_processing_charge":"No","external_id":{"isi":["000441266700006"],"pmid":["30089840"]},"title":"Genomics in neurodevelopmental disorders: an avenue to personalized medicine","quality_controlled":"1","publisher":"Springer Nature","oa":1,"has_accepted_license":"1","isi":1,"year":"2018","day":"07","publication":"Experimental & Molecular Medicine","date_published":"2018-08-07T00:00:00Z","doi":"10.1038/s12276-018-0129-7","date_created":"2019-01-27T22:59:11Z","_id":"5888","type":"journal_article","tmp":{"legal_code_url":"https://creativecommons.org/licenses/by/4.0/legalcode","image":"/images/cc_by.png","name":"Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)","short":"CC BY (4.0)"},"status":"public","date_updated":"2023-09-11T14:04:41Z","ddc":["570"],"file_date_updated":"2020-07-14T12:47:13Z","department":[{"_id":"GaNo"}],"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."}],"oa_version":"Published Version","pmid":1,"scopus_import":"1","month":"08","intvolume":" 50","publication_identifier":{"issn":["2092-6413"]},"publication_status":"published","file":[{"file_id":"5893","checksum":"4498301c8c53097c9a1a8ef990936eb5","content_type":"application/pdf","access_level":"open_access","relation":"main_file","date_created":"2019-01-28T15:18:02Z","file_name":"2018_EMM_Tarlungeanu.pdf","date_updated":"2020-07-14T12:47:13Z","file_size":1237482,"creator":"dernst"}],"language":[{"iso":"eng"}],"issue":"8","volume":50},{"title":"Neural stem cells in neuropsychiatric disorders","publist_id":"7268","author":[{"id":"42C9F57E-F248-11E8-B48F-1D18A9856A87","first_name":"Roberto","last_name":"Sacco","full_name":"Sacco, Roberto"},{"first_name":"Emanuele","full_name":"Cacci, Emanuele","last_name":"Cacci"},{"first_name":"Gaia","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178"}],"external_id":{"isi":["000427101600018"]},"article_processing_charge":"No","user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"ista":"Sacco R, Cacci E, Novarino G. 2018. Neural stem cells in neuropsychiatric disorders. Current Opinion in Neurobiology. 48(2), 131–138.","chicago":"Sacco, Roberto, Emanuele Cacci, and Gaia Novarino. “Neural Stem Cells in Neuropsychiatric Disorders.” Current Opinion in Neurobiology. Elsevier, 2018. https://doi.org/10.1016/j.conb.2017.12.005.","ama":"Sacco R, Cacci E, Novarino G. Neural stem cells in neuropsychiatric disorders. Current Opinion in Neurobiology. 2018;48(2):131-138. doi:10.1016/j.conb.2017.12.005","apa":"Sacco, R., Cacci, E., & Novarino, G. (2018). Neural stem cells in neuropsychiatric disorders. Current Opinion in Neurobiology. Elsevier. https://doi.org/10.1016/j.conb.2017.12.005","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.","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."},"doi":"10.1016/j.conb.2017.12.005","date_published":"2018-02-01T00:00:00Z","date_created":"2018-12-11T11:47:06Z","page":"131 - 138","day":"01","publication":"Current Opinion in Neurobiology","isi":1,"year":"2018","quality_controlled":"1","publisher":"Elsevier","department":[{"_id":"GaNo"}],"date_updated":"2023-09-13T09:01:56Z","status":"public","type":"journal_article","_id":"546","issue":"2","volume":48,"language":[{"iso":"eng"}],"publication_status":"published","month":"02","intvolume":" 48","scopus_import":"1","oa_version":"None","abstract":[{"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.","lang":"eng"}]},{"type":"journal_article","article_type":"original","status":"public","_id":"691","department":[{"_id":"GaNo"}],"date_updated":"2023-10-16T09:55:43Z","scopus_import":"1","main_file_link":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056005/","open_access":"1"}],"month":"01","intvolume":" 55","abstract":[{"text":"Background: Transport protein particle (TRAPP) is a multisubunit complex that regulates membrane trafficking through the Golgi apparatus. The clinical phenotype associated with mutations in various TRAPP subunits has allowed elucidation of their functions in specific tissues. The role of some subunits in human disease, however, has not been fully established, and their functions remain uncertain.\r\n\r\nObjective: We aimed to expand the range of neurodevelopmental disorders associated with mutations in TRAPP subunits by exome sequencing of consanguineous families.\r\n\r\nMethods: Linkage and homozygosity mapping and candidate gene analysis were used to identify homozygous mutations in families. Patient fibroblasts were used to study splicing defect and zebrafish to model the disease.\r\n\r\nResults: We identified six individuals from three unrelated families with a founder homozygous splice mutation in TRAPPC6B, encoding a core subunit of the complex TRAPP I. Patients manifested a neurodevelopmental disorder characterised by microcephaly, epilepsy and autistic features, and showed splicing defect. Zebrafish trappc6b morphants replicated the human phenotype, displaying decreased head size and neuronal hyperexcitability, leading to a lower seizure threshold.\r\n\r\nConclusion: This study provides clinical and functional evidence of the role of TRAPPC6B in brain development and function.","lang":"eng"}],"pmid":1,"oa_version":"Submitted Version","volume":55,"issue":"1","publication_identifier":{"issn":["0022-2593"]},"publication_status":"published","language":[{"iso":"eng"}],"project":[{"_id":"254BA948-B435-11E9-9278-68D0E5697425","name":"Probing development and reversibility of autism spectrum disorders","grant_number":"401299"}],"author":[{"last_name":"Marin Valencia","full_name":"Marin Valencia, Isaac","first_name":"Isaac"},{"id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","last_name":"Novarino"},{"first_name":"Anide","full_name":"Johansen, Anide","last_name":"Johansen"},{"first_name":"Başak","full_name":"Rosti, Başak","last_name":"Rosti"},{"first_name":"Mahmoud","full_name":"Issa, Mahmoud","last_name":"Issa"},{"first_name":"Damir","full_name":"Musaev, Damir","last_name":"Musaev"},{"first_name":"Gifty","full_name":"Bhat, Gifty","last_name":"Bhat"},{"full_name":"Scott, Eric","last_name":"Scott","first_name":"Eric"},{"full_name":"Silhavy, Jennifer","last_name":"Silhavy","first_name":"Jennifer"},{"full_name":"Stanley, Valentina","last_name":"Stanley","first_name":"Valentina"},{"first_name":"Rasim","full_name":"Rosti, Rasim","last_name":"Rosti"},{"last_name":"Gleeson","full_name":"Gleeson, Jeremy","first_name":"Jeremy"},{"last_name":"Imam","full_name":"Imam, Farhad","first_name":"Farhad"},{"last_name":"Zaki","full_name":"Zaki, Maha","first_name":"Maha"},{"last_name":"Gleeson","full_name":"Gleeson, Joseph","first_name":"Joseph"}],"publist_id":"7016","article_processing_charge":"No","external_id":{"isi":["000418199800007"],"pmid":["28626029"]},"title":"A homozygous founder mutation in TRAPPC6B associates with a neurodevelopmental disorder characterised by microcephaly epilepsy and autistic features","citation":{"chicago":"Marin Valencia, Isaac, Gaia Novarino, Anide Johansen, Başak Rosti, Mahmoud Issa, Damir Musaev, Gifty Bhat, et al. “A Homozygous Founder Mutation in TRAPPC6B Associates with a Neurodevelopmental Disorder Characterised by Microcephaly Epilepsy and Autistic Features.” Journal of Medical Genetics. BMJ Publishing Group, 2018. https://doi.org/10.1136/jmedgenet-2017-104627.","ista":"Marin Valencia I, Novarino G, Johansen A, Rosti B, Issa M, Musaev D, Bhat G, Scott E, Silhavy J, Stanley V, Rosti R, Gleeson J, Imam F, Zaki M, Gleeson J. 2018. A homozygous founder mutation in TRAPPC6B associates with a neurodevelopmental disorder characterised by microcephaly epilepsy and autistic features. Journal of Medical Genetics. 55(1), 48–54.","mla":"Marin Valencia, Isaac, et al. “A Homozygous Founder Mutation in TRAPPC6B Associates with a Neurodevelopmental Disorder Characterised by Microcephaly Epilepsy and Autistic Features.” Journal of Medical Genetics, vol. 55, no. 1, BMJ Publishing Group, 2018, pp. 48–54, doi:10.1136/jmedgenet-2017-104627.","short":"I. Marin Valencia, G. Novarino, A. Johansen, B. Rosti, M. Issa, D. Musaev, G. Bhat, E. Scott, J. Silhavy, V. Stanley, R. Rosti, J. Gleeson, F. Imam, M. Zaki, J. Gleeson, Journal of Medical Genetics 55 (2018) 48–54.","ieee":"I. Marin Valencia et al., “A homozygous founder mutation in TRAPPC6B associates with a neurodevelopmental disorder characterised by microcephaly epilepsy and autistic features,” Journal of Medical Genetics, vol. 55, no. 1. BMJ Publishing Group, pp. 48–54, 2018.","apa":"Marin Valencia, I., Novarino, G., Johansen, A., Rosti, B., Issa, M., Musaev, D., … Gleeson, J. (2018). A homozygous founder mutation in TRAPPC6B associates with a neurodevelopmental disorder characterised by microcephaly epilepsy and autistic features. Journal of Medical Genetics. BMJ Publishing Group. https://doi.org/10.1136/jmedgenet-2017-104627","ama":"Marin Valencia I, Novarino G, Johansen A, et al. A homozygous founder mutation in TRAPPC6B associates with a neurodevelopmental disorder characterised by microcephaly epilepsy and autistic features. Journal of Medical Genetics. 2018;55(1):48-54. doi:10.1136/jmedgenet-2017-104627"},"user_id":"2DF688A6-F248-11E8-B48F-1D18A9856A87","quality_controlled":"1","publisher":"BMJ Publishing Group","oa":1,"page":"48 - 54","doi":"10.1136/jmedgenet-2017-104627","date_published":"2018-01-01T00:00:00Z","date_created":"2018-12-11T11:47:57Z","isi":1,"year":"2018","day":"01","publication":"Journal of Medical Genetics"},{"ddc":["570","616"],"date_updated":"2023-09-07T12:38:59Z","supervisor":[{"last_name":"Novarino","full_name":"Novarino, Gaia","orcid":"0000-0002-7673-7178","id":"3E57A680-F248-11E8-B48F-1D18A9856A87","first_name":"Gaia"}],"file_date_updated":"2021-02-11T23:30:15Z","department":[{"_id":"GaNo"}],"_id":"395","pubrep_id":"992","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":"dissertation","language":[{"iso":"eng"}],"file":[{"date_created":"2019-04-05T09:19:17Z","file_name":"2018_Thesis_Tarlungeanu_source.docx","date_updated":"2021-02-11T23:30:15Z","file_size":43684035,"creator":"dernst","file_id":"6217","checksum":"9f5231c96e0ad945040841a8630232da","content_type":"application/vnd.openxmlformats-officedocument.wordprocessingml.document","embargo_to":"open_access","access_level":"closed","relation":"source_file"},{"creator":"dernst","date_updated":"2021-02-11T11:17:16Z","file_size":30511532,"date_created":"2019-04-05T09:19:17Z","file_name":"2018_Thesis_Tarlungeanu.pdf","access_level":"open_access","relation":"main_file","content_type":"application/pdf","checksum":"0c33c370aa2010df5c552db57a6d01e9","file_id":"6218","embargo":"2018-03-15"}],"degree_awarded":"PhD","publication_status":"published","publication_identifier":{"issn":["2663-337X"]},"related_material":{"record":[{"relation":"part_of_dissertation","status":"public","id":"1183"}]},"oa_version":"Published Version","acknowledged_ssus":[{"_id":"PreCl"},{"_id":"EM-Fac"},{"_id":"Bio"}],"abstract":[{"lang":"eng","text":"Autism spectrum disorders (ASD) are a group of genetic disorders often overlapping with other neurological conditions. Despite the remarkable number of scientific breakthroughs of the last 100 years, the treatment of neurodevelopmental disorders (e.g. autism spectrum disorder, intellectual disability, epilepsy) remains a great challenge. Recent advancements in geno mics, like whole-exome or whole-genome sequencing, have enabled scientists to identify numerous mutations underlying neurodevelopmental disorders. Given the few hundred risk genes that were discovered, the etiological variability and the heterogeneous phenotypic outcomes, the need for genotype -along with phenotype- based diagnosis of individual patients becomes a requisite. Driven by this rationale, in a previous study our group described mutations, identified via whole - exome sequencing, in the gene BCKDK – encoding for a key regulator of branched chain amin o acid (BCAA) catabolism - as a cause of ASD. Following up on the role of BCAAs, in the study described here we show that the solute carrier transporter 7a5 (SLC7A5), a large neutral amino acid transporter localized mainly at the blood brain barrier (BBB), has an essential role in maintaining normal levels of brain BCAAs. In mice, deletion of Slc7a5 from the endothelial cells of the BBB leads to atypical brain amino acid profile, abnormal mRNA translation and severe neurolo gical abnormalities. Additionally, deletion of Slc7a5 from the neural progenitor cell population leads to microcephaly. Interestingly, we demonstrate that BCAA intracerebroventricular administration ameliorates abnormal behaviors in adult mutant mice. Furthermore, whole - exome sequencing of patients diagnosed with neurological dis o r ders helped us identify several patients with autistic traits, microcephaly and motor delay carrying deleterious homozygous mutations in the SLC7A5 gene. In conclusion, our data elucidate a neurological syndrome defined by SLC7A5 mutations and support an essential role for t he BCAA s in human bra in function. Together with r ecent studies (described in chapter two) that have successfully made the transition into clinical practice, our findings on the role of B CAAs might have a crucial impact on the development of novel individualized therapeutic strategies for ASD. "}],"month":"03","alternative_title":["ISTA Thesis"],"user_id":"c635000d-4b10-11ee-a964-aac5a93f6ac1","citation":{"chicago":"Tarlungeanu, Dora-Clara. “The Branched Chain Amino Acids in Autism Spectrum Disorders .” Institute of Science and Technology Austria, 2018. https://doi.org/10.15479/AT:ISTA:th_992.","ista":"Tarlungeanu D-C. 2018. The branched chain amino acids in autism spectrum disorders . Institute of Science and Technology Austria.","mla":"Tarlungeanu, Dora-Clara. The Branched Chain Amino Acids in Autism Spectrum Disorders . Institute of Science and Technology Austria, 2018, doi:10.15479/AT:ISTA:th_992.","ieee":"D.-C. Tarlungeanu, “The branched chain amino acids in autism spectrum disorders ,” Institute of Science and Technology Austria, 2018.","short":"D.-C. Tarlungeanu, The Branched Chain Amino Acids in Autism Spectrum Disorders , Institute of Science and Technology Austria, 2018.","ama":"Tarlungeanu D-C. The branched chain amino acids in autism spectrum disorders . 2018. doi:10.15479/AT:ISTA:th_992","apa":"Tarlungeanu, D.-C. (2018). The branched chain amino acids in autism spectrum disorders . Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:th_992"},"title":"The branched chain amino acids in autism spectrum disorders ","article_processing_charge":"No","publist_id":"7434","author":[{"first_name":"Dora-Clara","id":"2ABCE612-F248-11E8-B48F-1D18A9856A87","last_name":"Tarlungeanu","full_name":"Tarlungeanu, Dora-Clara"}],"project":[{"name":"Transmembrane Transporters in Health and Disease","grant_number":"F03523","call_identifier":"FWF","_id":"25473368-B435-11E9-9278-68D0E5697425"}],"day":"01","year":"2018","has_accepted_license":"1","date_created":"2018-12-11T11:46:14Z","date_published":"2018-03-01T00:00:00Z","doi":"10.15479/AT:ISTA:th_992","page":"88","oa":1,"publisher":"Institute of Science and Technology Austria"}]