المؤلفون: Léa Perra, Viviane Balloy, Tobias Foussignière, Didier Moissenet, Hortense Petat, Imran N. Mungrue, Lhousseine Touqui, Harriet Corvol, Michel Chignard, Loic Guillot

المساهمون: Sorbonne Université (SU), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Louisiana State University (LSU), Institut Pasteur [Paris], Mucoviscidose et bronchopathies chroniques : biopathologie et phénotypes cliniques (EA 2511), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Service de Pneumologie pédiatrique [CHU Trousseau], CHU Trousseau [APHP], MC received a grant from the French cystic fibrosis nonprofit organizations Vaincre La Mucoviscidose and Gregory Lemarchal. LP received a Ph.D. fellowship from the French cystic fibrosis nonprofit organization Vaincre La Mucoviscidose., Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), CHU Saint-Antoine [APHP], CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 (UPD5), Service de Pneumologie Pédiatrique [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Trousseau [APHP], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut Pasteur [Paris] (IP)

المصدر: Frontiers in Immunology
Frontiers in Immunology, Frontiers, 2018, 9, pp.2823. ⟨10.3389/fimmu.2018.02823⟩
Frontiers in Immunology, Vol 9 (2018)
Frontiers in Immunology, 2018, 9, pp.2823. ⟨10.3389/fimmu.2018.02823⟩

مصطلحات موضوعية: Adult, Male, 0301 basic medicine, lcsh:Immunologic diseases. Allergy, Small interfering RNA, Immunology, Bronchi, Inflammation, medicine.disease_cause, Cystic fibrosis, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, cystic fibrosis, 03 medical and health sciences, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, Humans, Immunology and Allergy, Pseudomonas Infections, Original Research, Aged, bronchial epithelium, Lung, biology, Chemistry, Pseudomonas aeruginosa, Epithelial Cells, Middle Aged, medicine.disease, Molecular biology, 3. Good health, ChaC glutathione-specific γ-glutamylcyclotransferase 1, 030104 developmental biology, medicine.anatomical_structure, Real-time polymerase chain reaction, Gene Expression Regulation, A549 Cells, Apoptosis, inflammation, biology.protein, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, medicine.symptom, lcsh:RC581-607, ER stress, gamma-Glutamylcyclotransferase, Flagellin

الوصف: International audience; In cystic fibrosis (CF), Pseudomonas aeruginosa (Pa) colonizes the lungs, leading to chronic inflammation of the bronchial epithelium. ChaC glutathione-specific γ-glutamylcyclotransferase 1 (CHAC1) mRNA is differentially expressed in primary human airway epithelial cells from bronchi (hAECBs) from patients with CF and healthy patients at baseline and upon infection with Pa. CHAC1 degrades glutathione and is associated with ER stress and apoptosis pathways. In this study, we examined the roles of CHAC1 in the inflammatory response and apoptosis in lung epithelial cells. First, we confirmed by reverse transcription quantitative polymerase chain reaction that CHAC1 mRNA was overexpressed in hAECBs from patients without CF compared with the expression in hAECBs from patients with CF upon Pa (PAK strain) infection. Moreover, the Pa virulence factors LPS and flagellin were shown to induce CHAC1 expression in cells from patients without CF. Using NCI-H292 lung epithelial cells, we found that LPS-induced CHAC1 mRNA expression was PERK-independent and involved ATF4. Additionally, using CHAC1 small interfering RNA, we showed that reduced CHAC1 expression in the context of LPS and flagellin stimulation was associated with modulation of inflammatory markers and alteration of NF-κB signaling. Finally, we showed that Pa was not able to induce apoptosis in NCI-H292 cells. Our results suggest that CHAC1 is involved in the regulation of inflammation in bronchial cells during Pa infection and may explain the excessive inflammation present in the respiratory tracts of patients with CF.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a775bf42700f5c5375290066efded6f5Test
https://hal.sorbonne-universite.fr/hal-01977256/file/fimmu-09-02823.pdfTest

المؤلفون: Stéphanie Leruez, Judith Kouassi Nzoughet, Vincent Procaccio, Charlotte Veyrat-Durebex, Mariame-Selma Kane, Pascal Reynier, Cinzia Bocca, Chadi Homedan, Dominique Bonneau, Marc Ferré, Arnaud Chevrollier, Guy Lenaers, Patrizia Amati-Bonneau, Gilles Simard, Dan Milea, Christophe Verny, Juan Manuel Chao de la Barca

المساهمون: Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

المصدر: Investigative Ophthalmology & Visual Science
Investigative Ophthalmology & Visual Science, Association for Research in Vision and Ophthalmology, 2018, 59, pp.185-195. ⟨10.1167/iovs.17-23027⟩

مصطلحات موضوعية: 0301 basic medicine, Adult, Male, Adolescent, Genotype, GTP Phosphohydrolases, 03 medical and health sciences, chemistry.chemical_compound, Young Adult, Atrophy, Metabolomics, Optic Atrophy, Autosomal Dominant, medicine, OMIM : Online Mendelian Inheritance in Man, Humans, Matrix-Assisted Laser Desorption-Ionization, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, Purine metabolism, Inosine, Child, Hypoxanthine, Chromatography, High Pressure Liquid, Phosphocholine, Chromatography, métabolome, Spectrometry, Middle Aged, Mass, medicine.disease, Optic Atrophy, 030104 developmental biology, Phenotype, chemistry, Biochemistry, Autosomal Dominant, Purines, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, High Pressure Liquid, Metabolome, Optic Atrophy 1, Female, medicine.drug

الوصف: International audience; Purpose: Dominant optic atrophy (DOA; MIM [Mendelian Inheritance in Man] 165500), resulting in retinal ganglion cell degeneration, is mainly caused by mutations in the optic atrophy 1 (OPA1) gene, which encodes a dynamin guanosine triphosphate (GTP)ase involved in mitochondrial membrane processing. This work aimed at determining whether plasma from OPA1 pathogenic variant carriers displays a specific metabolic signature.Methods: We applied a nontargeted clinical metabolomics pipeline based on ultra-high-pressure liquid chromatography coupled to high-resolution mass spectrometry (UHPLC-HRMS) allowing the exploration of 500 polar metabolites in plasma. We compared the plasma metabolic profiles of 25 patients with various OPA1 pathogenic variants and phenotypes to those of 20 healthy controls. Statistical analyses were performed using univariate and multivariate (principal component analysis [PCA], orthogonal partial least-squares discriminant analysis [OPLS-DA]) methods and a machine learning approach, the Biosigner algorithm.Results: A robust and relevant predictive model characterizing OPA1 individuals was obtained, based on a complex panel of metabolites with altered concentrations. An impairment of the purine metabolism, including significant differences in xanthine, hypoxanthine, and inosine concentrations, was at the foreground of this signature. In addition, the signature was characterized by differences in urocanate, choline, phosphocholine, glycerate, 1-oleoyl-rac-glycerol, rac-glycerol-1-myristate, aspartate, glutamate, and cystine concentrations.Conclusions: This first metabolic signature reported in the plasma of patient carrying OPA1 pathogenic variants highlights the unexpected involvement of purine metabolism in the pathophysiology of DOA.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::faa9facbc249a482aaadd3c96d7ce03eTest
https://hal.archives-ouvertes.fr/hal-01964499Test

المؤلفون: Franck Tirode, A. Michot, Gaëtan MacGrogan, Daniel Pissaloux, Yanis Zekri, Jean-Yves Blay, Tom Lesluyes, Florence Pedeutour, Dominique Ranchère-Vince, Frédéric Chibon, Lucile Delespaul, Agnès Lancon, Frédérique Keslair, Ilaria Di Mauro, Jean-Michel Coindre, Arnaud de la Fouchardière, Marie Karanian, Nathalie Cardot-Leccia, François Le Loarer, Laurent Alberti, Gaëlle Pérot, Adeline Duc, Sandrine Paindavoine, Valérie Kubiniek, Virginie Perrin, Bérengère Dadone-Montaudié

المساهمون: TIRODE, Franck, Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), UNICANCER, Université de Bordeaux (UB), Université Nice Sophia Antipolis (... - 2019) (UNS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Centre de Recherche en Cancérologie de Lyon (CRCL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié - CRLCC Bordeaux, Institut Bergonié - CRLCC Bordeaux

المصدر: Modern Pathology
Modern Pathology, 2018, 31 (11), pp.1683-1693. ⟨10.1038/s41379-018-0089-4⟩
Modern Pathology, Nature Publishing Group: Open Access Hybrid Model Option B, 2018, 31 (11), pp.1683-1693. ⟨10.1038/s41379-018-0089-4⟩

مصطلحات موضوعية: 0301 basic medicine, Adult, Male, Pathology, medicine.medical_specialty, Skin Neoplasms, Oncogene Proteins, Fusion, Chromosomal translocation, PDGFRB, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Pathology and Forensic Medicine, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, CDKN2A, Pathognomonic, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Dermatofibrosarcoma protuberans, Humans, Aged, Gene Rearrangement, Platelet-Derived Growth Factor, Lymphokines, PDGFB, medicine.diagnostic_test, Dermatofibrosarcoma, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Gene rearrangement, Proto-Oncogene Proteins c-sis, Middle Aged, medicine.disease, Collagen Type I, alpha 1 Chain, 030104 developmental biology, 030220 oncology & carcinogenesis, Child, Preschool, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Female, Fluorescence in situ hybridization

الوصف: International audience; Dermatofibrosarcoma protuberans is underlined by recurrent collagen type I alpha 1 chain-platelet-derived growth factor B chain (COL1A1-PDGFB) fusions but ~ 4% of typical dermatofibrosarcoma protuberans remain negative for this translocation in routine molecular screening. We investigated a series of 21 cases not associated with the pathognomonic COL1A1-PDGFB fusion on routine fluorescence in situ hybridization (FISH) testing. All cases displayed morphological and clinical features consistent with the diagnosis of dermatofibrosarcoma protuberans. RNA-sequencing analysis was successful in 20 cases. The classical COL1A1-PDGFB fusion was present in 40% of cases (n = 8/20), and subsequently confirmed with a COL1A1 break-apart FISH probe in all but one case (n = 7/8). 55% of cases (n = 11/20) displayed novel PDGFD rearrangements; PDGFD being fused either to the 5' part of COL6A3 (2q37.3) (n = 9/11) or EMILIN2 (18p11) (n = 2/11). All rearrangements led to in-frame fusion transcripts and were confirmed at genomic level by FISH and/or array-comparative genomic hybridization. PDGFD-rearranged dermatofibrosarcoma protuberans presented clinical outcomes similar to typical dermatofibrosarcoma protuberans. Notably, the two EMILIN2-PDGFD cases displayed fibrosarcomatous transformation and homozygous deletions of CDKN2A at genomic level. We report the first recurrent molecular variant of dermatofibrosarcoma protuberans involving PDGFD, which functionally mimic bona fide COL1A1-PDGFB fusions, leading presumably to a similar autocrine loop-stimulating PDGFRB. This study also emphasizes that COL1A1-PDGFB fusions can be cytogenetically cryptic on FISH testing in a subset of cases, thereby representing a diagnostic pitfall that pathologists should be aware of.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::662783a71d2ff4cccb9c363c2427a69cTest
https://www.hal.inserm.fr/inserm-02440547Test

المؤلفون: Anna Maciejewski-Duval, Cloé Comarmond, J Fouret, A. Le Joncour, Fabien Koskas, Patrice Cacoub, Alban Leroyer, M. Zaidan, Philippe Cluzel, Marlène Garrido, D. Saadoun, A.C. Desbois

المساهمون: Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Departement Hospitalo- Universitaire - Inflammation, Immunopathologie, Biothérapie [Paris] (DHU - I2B), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Service de médecine interne et d'immunologie clinique [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Vascular research center of Marseille (VRCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Néphrologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'Anatomie et cytologie pathologiques [CHU Pitié-Salpêtrière] (ACP), Service de radiologie cardiovasculaire et interventionnelle [CHU Pitié-Salpêtrière], Laboratoire d'Imagerie Biomédicale (LIB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Trousseau [APHP], Service de Département de médecine interne et immunologie clinique [CHU Pitié-Salpêtrière] (DMIIC), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Immunologie - Immunopathologie - Immunothérapie (I3), CHU Pitié-Salpêtrière [APHP]-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre recherche en CardioVasculaire et Nutrition (C2VN), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service d'anatomopathologie [CHU Pitié-Salpétrière], CHU Pitié-Salpêtrière [APHP], Service d'imagerie cardiovasculaire et de radiologie interventionnelle [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire d'Imagerie Biomédicale [Paris] (LIB)

المصدر: Journal of Autoimmunity
Journal of Autoimmunity, Elsevier, 2018, 94, pp.99-109. ⟨10.1016/j.jaut.2018.07.013⟩
Journal of Autoimmunity, 2018, 94, pp.99-109. ⟨10.1016/j.jaut.2018.07.013⟩

مصطلحات موضوعية: Male, 0301 basic medicine, mTORC1, 030204 cardiovascular system & hematology, T-Lymphocytes, Regulatory, Pathogenesis, 0302 clinical medicine, Immunology and Allergy, Phosphorylation, Aorta, Giant cell arteritis, TOR Serine-Threonine Kinases, Interleukin-17, Middle Aged, 3. Good health, medicine.anatomical_structure, mTOR, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, medicine.symptom, Signal Transduction, Takayasu arteritis, Adult, Vasculitis, T cell, Myocytes, Smooth Muscle, Primary Cell Culture, Immunology, Inflammation, Mechanistic Target of Rapamycin Complex 1, Proinflammatory cytokine, Interferon-gamma, 03 medical and health sciences, Large vessel vasculitis, medicine, Humans, Rapamycin, PI3K/AKT/mTOR pathway, Aged, Cell Proliferation, Sirolimus, business.industry, Interleukins, Endothelial Cells, Th1 Cells, 030104 developmental biology, Gene Expression Regulation, Case-Control Studies, Cancer research, Th17 Cells, business

الوصف: International audience; Background:Mammalian target of rapamycin complex 1 (mTORC 1) drives the proinflammatory expansion of T helper (TH) type 1, TH17 cells and controls fibroblast proliferation, typical features of large vessel vasculitis (LVV) pathogenesis. Molecular pathways involved in arterial lesions of LVV are unknown.Methods: We evaluate mTORC pathway activation in vascular aorta lesions and in T cell homeostasis of patients with LVV.Results: Proliferation of both endothelial cells and vascular smooth-muscle cells was shown in vascular lesions in LVV. The vascular endothelium of proliferating aorta vessels from patients with LVV showed indications of activation of the mTORC1 pathway (S6RP phosphorylation). In cultured vascular endothelial cells, sera from patients with LVV stimulated mTORC1 through the phosphorylation of S6RP. mTORC1 activation was found also in Th1 and Th17 cells both systemically and in inflamed vessels. Patients with LVV exhibited a diminished S6RP phosphorylation in Tregs. Inhibition of mTORC1 pathway with rapamycin, increase Tregs and decrease effector CD4+IFNγ+, CD4+IL17+ and CD4+IL21+ T cells in patients with LVV.Conclusions: We provided evidence that mTORC1 pathway has a central role in driving T cell inflammation and vascular lesions in LVV. Targeting mTORC pathway may represent a new therapeutic option in patients with LVV.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e77b8c790c978dcde875e477cd3eead9Test
https://hal.sorbonne-universite.fr/hal-01930122Test

المؤلفون: Christian P. Müller, Gunter Schumann, Roberto Toro, Susanne Erk, Stephanie H. Witt, Cathy Fernandes, Jean Christophe Poncer, Franziska Degenhardt, Andreas Meyer-Lindenberg, Deepak Srivastava, Barbara Ruggeri, A. Fernandes, Marie-Laure Paillère Martinot, Andreas Heinz, Lourdes Martinez Medina, Agnieszka Kepa, Henrik Walter, Sylvane Desrivières, Sabine Lévi, Jean-Luc Martinot

المساهمون: Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Gènes, Synapses et Cognition, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut du Fer à Moulin, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), University of Bonn, Universität Heidelberg [Heidelberg], Central Institute of Mental Health [Mannheim], Medical Faculty [Mannheim], Neuroimagerie en psychiatrie (U1000), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Maison de Solenn [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], Friedrich Alexander University [Erlangen-Nürnberg], This work was funded by Wellcome Trust grant reference 090532/Z/09/Z and MRC Hub grant G0900747 91070. This work received further support from the European Union-funded FP6 Integrated Project IMAGEN (reinforcement-related behavior in normal brain function and psychopathology, LSHM-CT- 2007-037286). S.D and G.S. are also supported in part by the NIH BD2K award, U54EB020403, the FP7 projects IMAGEMEND (602450, IMAging GEnetics for MENtal Disorders) and MATRICS (603016), the Innovative Medicine Initiative Project EU-AIMS (115300-2), a Medical Research Council Programme Grant ‘Developmental pathways into adolescent substance abuse’ (93558), the Swedish funding agency FORMAS, the Medical Research Council and the Wellcome Trust (Behavioural and Clinical Neuroscience Institute, University of Cambridge), the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London, the Bundesministeriumfür Bildung und Forschung (BMBF grants 01GS08152, 01EV0711, eMED SysAlc01ZX1311A, Forschungsnetze AERIAL and BipoLife) and the Deutsche Forschungsgemeinschaft (DFG grants FOR 1617, SFB 940 and SM 80/5-2)., European Project: 39513,IMAGEN, European Project: 602450,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,IMAGEMEND(2013), European Project: 603016,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,MATRICS(2014), European Project: 115300,EC:FP7:SP1-JTI,IMI-JU-03-2010,EU-AIMS(2012), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Gènes, Synapses et Cognition (CNRS - UMR3571 ), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Universität Bonn = University of Bonn, Universität Heidelberg [Heidelberg] = Heidelberg University, University Hospital Mannheim | Universitätsmedizin Mannheim, Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Sud - Paris 11 (UP11), Department of Genomics, Génétique humaine et Fonctions cognitives - Human Genetics and Cognitive Functions, Centre National de la Recherche Scientifique ( CNRS ) -Institut Pasteur [Paris], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), King's College, Department of Genomics, Life and Brain Center, Université de Bonn, Department of Genetic Epidemiology in Psychiatry [Mannhein], Universität Heidelberg [Heidelberg]-Central Institute of Mental Health Mannheim, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Sorbonne Université, Neuroimagerie en psychiatrie ( U1000 ), Université Paris-Sud - Paris 11 ( UP11 ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), IFR49, Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ), Service Hospitalier Frédéric Joliot ( SHFJ ), Direction de Recherche Fondamentale (CEA) ( DRF (CEA) ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Saclay, Université Paris-Sud - Paris 11 ( UP11 ), Université Paris Descartes - Paris 5 ( UPD5 ), Université Sorbonne Paris Cité ( USPC ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], Institut für Chemie und Biochemie, Anorganische Chemie, Freie Universität Berlin, MRC- SGDP Centre, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London SE5 8AF, UK

المصدر: Neuropsychopharmacology
Neuropsychopharmacology, Nature Publishing Group, 2017, 42 (13), pp.2516-2526. ⟨10.1038/npp.2017.91⟩
Neuropsychopharmacology, 2017, 42 (13), pp.2516-2526. ⟨10.1038/npp.2017.91⟩
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
Kepa, A M, Martinez Medina, L, Erk, S, Srivastava, D P, Fernandes, A, Toro, R, Lévi, S, Ruggeri, B, Fernandes, C, Degenhardt, F, Witt, S H, Meyer-Lindenberg, A, Poncer, J-C, Martinot, J-L, Paillere-Martinot, M-L, Müller, C P, Heinz, A, Walter, H, Schumann, G & Desrivieres, S 2017, ' Associations of the Intellectual Disability Gene MYT1L with Helix-Loop-Helix Gene Expression, Hippocampus Volume and Hippocampus Activation During Memory Retrieval ', Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology, vol. 42, pp. 2516–2526 . https://doi.org/10.1038/npp.2017.91Test
Neuropsychopharmacology, Nature Publishing Group, 2017, 42 (13), pp.2516-2526. 〈10.1038/npp.2017.91〉

مصطلحات موضوعية: Adult, Inhibitor of Differentiation Protein 1, Male, 0301 basic medicine, Neurogenesis, [SDV]Life Sciences [q-bio], Gene Expression, Hippocampus, Nerve Tissue Proteins, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, 0302 clinical medicine, Neural Stem Cells, Memory, Gene expression, Journal Article, Basic Helix-Loop-Helix Transcription Factors, Humans, Transcription factor, ComputingMilieux_MISCELLANEOUS, Genetic Association Studies, Pharmacology, Gene knockdown, [ SDV ] Life Sciences [q-bio], Long-term potentiation, Organ Size, TCF4, Magnetic Resonance Imaging, Neural stem cell, Neoplasm Proteins, Psychiatry and Mental health, HEK293 Cells, 030104 developmental biology, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Gene Knockdown Techniques, Female, Inhibitor of Differentiation Proteins, Neuroscience, 030217 neurology & neurosurgery, Transcription Factors

الوصف: The fundamental role of the brain-specific myelin transcription factor 1-like (MYT1L) gene in cases of intellectual disability and in the aetiology of neurodevelopmental disorders is increasingly recognised. Yet, its function remains under-investigated. Here, we identify a network of helix-loop-helix (HLH) transcriptional regulators controlled by MYT1L, as indicated by our analyses in human neural stem cells and in the human brain. Using cell-based knockdown approaches and microarray analyses we found that (i) MYT1L is required for neuronal differentiation and identified ID1, a HLH inhibitor of premature neurogenesis, as a target. (2) While MYT1L prevented expression of ID1, it induced expression of a large number of terminal differentiation genes. (3) Consistently, expression of MYT1L in the human brain coincided with neuronal maturation and inversely correlated with that of ID1 and ID3 throughout the lifespan. (4) Genetic polymorphisms that reduced expression of MYT1L in the hippocampus resulted in increased expression of ID1 and ID3, decreased levels of the proneural basic HLH (bHLH) transcriptional regulators TCF4 and NEUROD6 and decreased expression of genes involved in long-term potentiation and synaptic transmission, cancer and neurodegeneration. Furthermore, our neuroimaging analyses indicated that MYT1L expression associated with hippocampal volume and activation during episodic memory recall, as measured by blood-oxygen-level dependent (BOLD) signals. Overall, our findings suggest that MYT1L influences memory-related processes by controlling a neuronal proliferation/differentiation switch of ID-bHLH factors.Neuropsychopharmacology accepted article preview online, 04 May 2017. doi:10.1038/npp.2017.91.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f3731b2ff79c53fafc5bc7d380e59afbTest
https://hal-pasteur.archives-ouvertes.fr/pasteur-01967213Test

المؤلفون: Jean-Christophe Vaillant, Nelson Dusetti, Jean-François Emile, Jean-Baptiste Bachet, Pascal Hammel, Anastasia R. Goloudina, Aurelie Scriva, Jean-Robert Delpero, Jean-François Fléjou, François Paye, Juan L. Iovanna, Christophe Louvet, Thierry André, Jean Closset, Jean-Luc Van Laethem, Alex Duval, Renato Micelli Lupinacci, Martine Antoine, Alain Sauvanet, Issam Abd Alsamad, Jérôme Cros, Vincent Jonchère, Olivier Buhard, Sylvie Dumont, Armelle Bardier-Dupas, Ada Collura, Raphaël Maréchal, Pieter Demetter, Anita Rodenas, Pascale Cervera, Magali Svrcek

المساهمون: Zayed Military Hospital, Department of Pathology, Hôpital Erasmes, Laboratoire électrotechnique et électronique industrielle (LEEI), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Assistance publique-Hôpitaux de Paris - Espace éthique (AP-HP Espace éthique), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Unité Mixte de Service d'Imagerie et de Cytométrie (UMS LUMIC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, Service de chirurgie hepato-pancreato-biliaire, Hôpital Beaujon-Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service d'Oncologie Médicale [Montsouris], Institut Mutualiste de Montsouris (IMM), Laboratoire épidémiologie et oncogénèse des tumeurs digestives, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Erasme Hospital, Brussels, Service d’Anatomie et cytologie pathologiques [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Tenon [APHP], Service d'anatomie pathologique [CHU Tenon], Service d'anatomie et cytologie pathologiques [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Centre de Recherche en Cancérologie de Marseille (CRCM), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Aix Marseille Université (AMU), Physiopathologie du stress pancréatique, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Saint-Antoine (CR Saint-Antoine), Pathologies biliaires, fibrose et cancer du foie (Inserm UMR_S 938), CHU Saint-Antoine [APHP]-Centre de Recherche Saint-Antoine (CR Saint-Antoine), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université de Montpellier (UM), Service de chirurgie générale et digestive [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Service d'Oncologie Médicale [CHU Saint -Antoine], Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Hôpital Erasme [Bruxelles] (ULB), Faculté de Médecine [Bruxelles] (ULB), Université libre de Bruxelles (ULB)-Université libre de Bruxelles (ULB), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université, Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Montpellier (UM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Groupe Hospitalier Diaconesses Croix Saint-Simon, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC), Hôpital Erasme [Bruxelles], Hôpital Beaujon [AP-HP], Université Paris Diderot - Paris 7 (UPD7), CHU Saint-Antoine [AP-HP], Hôpitaux Universitaires de l'Est Parisien [Paris] (HUEP), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Hôpital Ambroise Paré [AP-HP], CHI Créteil, CHU Tenon [AP-HP], Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [APHP], Laboratoire électrotechnique et électronique industrielle ( LEEI ), Institut National Polytechnique [Toulouse] ( INP ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique-Hôpitaux de Paris - Espace éthique ( AP-HP Espace éthique ), Assistance publique - Hôpitaux de Paris (AP-HP), Unité Mixte de Service d'Imagerie et de Cytométrie ( UMS LUMIC ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Hôpital Beaujon, Institut Mutualiste de Montsouris ( IMM ), Laboratoire de Mathématiques Informatique et Applications ( LAMIA ), Université des Antilles et de la Guyane ( UAG ), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Service d'anatomie et cytologie pathologiques, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Centre de Recherche en Cancérologie de Marseille ( CRCM ), Aix Marseille Université ( AMU ) -Institut Paoli-Calmettes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche Saint-Antoine ( CR Saint-Antoine ), Pathologies biliaires, fibrose et cancer du foie ( Inserm UMR_S 938 ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Saint-Antoine [APHP], Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer ( LabEx LipSTIC ), Institut National de la Recherche Agronomique ( INRA ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École pratique des hautes études ( EPHE ) -Institut Gustave Roussy ( IGR ) -Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ) -Université de Bourgogne ( UB ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université de Franche-Comté ( UFC ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP]

المصدر: Gastroenterology
Gastroenterology, WB Saunders, 2017, 154 (4), pp.1061-1065. ⟨10.1053/j.gastro.2017.11.009⟩
Gastroenterology, 2018, 154 (4), pp.1061-1065. ⟨10.1053/j.gastro.2017.11.009⟩
Gastroenterology, WB Saunders, 2017, 154 (4), pp.1061-1065. 〈10.1053/j.gastro.2017.11.009〉

مصطلحات موضوعية: 0301 basic medicine, Oncology, Male, Time Factors, endocrine system diseases, [SDV]Life Sciences [q-bio], CD8-Positive T-Lymphocytes, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, PMS2, Cytokine Production, Mismatch Repair Endonuclease PMS2, Aged, 80 and over, Gastroenterology, Middle Aged, Lynch syndrome, 3. Good health, DNA-Binding Proteins, MutS Homolog 2 Protein, Phenotype, 030220 oncology & carcinogenesis, Female, Microsatellite Instability, MutL Protein Homolog 1, Carcinoma, Pancreatic Ductal, Adult, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, MLH1, Disease-Free Survival, 03 medical and health sciences, Pancreatic Cancer, Lymphocytes, Tumor-Infiltrating, Internal medicine, Pancreatic cancer, medicine, Biomarkers, Tumor, Humans, Genetic Predisposition to Disease, neoplasms, Aged, Hepatology, Intraductal papillary mucinous neoplasm, [ SDV ] Life Sciences [q-bio], T-cell Activation, Microsatellite instability, nutritional and metabolic diseases, Marker, medicine.disease, digestive system diseases, MSH6, Pancreatic Neoplasms, 030104 developmental biology, MSH2, Neoplasms, Cystic, Mucinous, and Serous

الوصف: International audience; Microsatellite instability (MSI) caused by mismatch repair deficiency (dMMR) is detected in a small proportion of pancreatic ductal adenocarcinomas (PDACs). dMMR and MSI have been associated with responses of metastatic tumors, including PDACs, to immune checkpoint inhibitor therapy. We performed immunohistochemical analyses of a 445 PDAC specimens, collected from consecutive patients at multiple centers, to identify those with dMMR, based on loss of mismatch repair proteins MLH1, MSH2, MSH6, and/or PMS2. We detected dMMR in 1.6% of tumor samples; we found dMMR in a larger proportion of intraductal papillary mucinous neoplasms-related tumors (4/58, 6.9%) than non- intraductal papillary mucinous neoplasms PDAC (5/385, 1.3%) (P = .02). PDACs with dMMR contained potentially immunogenic mutations because of MSI in coding repeat sequences. PDACs with dMMR or MSI had a higher density of CD8+ T cells at the invasive front than PDACs without dMMR or MSI (P = .08; Fisher exact test). A higher proportion of PDACs with dMMR or MSI expressed the CD274 molecule (PD-L1, 8/9) than PDACs without dMMR or MSI (4/10) (P = .05). Times of disease-free survival and overall survival did not differ significantly between patients with PDACs with dMMR or MSI vs without dMMR or MSI. Studies are needed to determine whether these features of PDACs with dMMR or MSI might serve as prognostic factors.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::defce44e0e794098f7bcb962ae7ddbc1Test
https://hal.archives-ouvertes.fr/hal-01791680Test

المؤلفون: Catherine Yardin, Sylvie Bourthoumieu, Cécile Laroche-Raynaud, Amelia Dobrescu, Valentine Marquet

المساهمون: Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centre de recherche de l'hôpital Sainte Justine, CHU Sainte Justine [Montréal], Service d'Histologie, cytologie, cytogénétique, biologie cellulaire [CHU Limoges], CHU Limoges, Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT]

المصدر: European Journal of Medical Genetics
European Journal of Medical Genetics, Elsevier, 2017, 60 (11), pp.583-588. ⟨10.1016/j.ejmg.2017.08.009⟩

مصطلحات موضوعية: Adult, Male, 0301 basic medicine, Chromosome engineering, [SDV]Life Sciences [q-bio], Chromosome Disorders, Chromosome 9, Chromosomal translocation, Chromosomal rearrangement, Biology, Translocation, Genetic, Chromosome Breakpoints, 03 medical and health sciences, Chromosome Duplication, Gene duplication, Genetics, Humans, Global developmental delay, Child, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, Breakpoint, Infant, General Medicine, Telomere, Microdeletion syndrome, Pedigree, Phenotype, 030104 developmental biology, Chromosomes, Human, Pair 1, Female

الوصف: Unlike the 1p36 microdeletion syndrome, which has been extensively described, 1p36 microduplications have rarely been reported. We describe a three years old boy presenting with a severe global developmental delay and a few dysmorphic features. Cytogenetic analyses revealed a maternally inherited 3.35 Mb microduplication of chromosomal band 1p36.3. The maternal grandfather is also carrier of the same chromosomal rearrangement. Interestingly, the duplicated 1p36.3 segment was found to be localized at the telomeric end of the long arms of a chromosome 9, probably deriving from a 1p36.3-9qter non-reciprocal translocation. This particular type of chromosomal translocation has rarely been reported, and its mechanism is unclear. The phenotypical features associated with 1p36.3 microduplication vary due to the non-recurrent breakpoints of the rearrangements in this particular region. However when compiling the few described cases the phenotypical spectrum seems to include mainly developmental delay, mild facial dysmorphism, and neurological, cardiac and skeletal anomalies. The description of new patients carrying a 1p36.3 duplication like ours will lead to further delineation of the phenotypical spectrum and may help to find critical regions and causative genes implicated in the phenotype.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e2a966b6bfa323da84902a008f72629eTest
https://hal.archives-ouvertes.fr/hal-02436894Test

المؤلفون: Antoine Rousseau, David Boutolleau, Karine Titier, Tristan Bourcier, Christophe Chiquet, Michel Weber, Joseph Colin, Julie Gueudry, Mohamed M'Garrech, Bahram Bodaghi, Sonia Burrel, Henri Agut, Claire Deback, Marc Labetoulle, Jean-Paul Berrod, Eric Gabison, Louis Hoffart, Marc Muraine, David Touboul, Cédric Schweitzerr

المساهمون: CHU Bordeaux [Bordeaux], Hôpital Bicêtre, Service de virologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service d'Ophtalmologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'Ophtalmologie [CHU Pitié-Salpêtrière], CHU Strasbourg, Centre d'Immunologie et de Maladies Infectieuses (CIMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre Hospitalier Universitaire [Grenoble] (CHU), Hôpital Paul Brousse, Hôpital Paul Brousse-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Service de Médecine Interne [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Epidémiosurveillance de protozooses à transmission alimentaire et vectorielle (ESCAPE), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Université de Reims Champagne-Ardenne (URCA), Peau et environnement: réponses normales et pathologiques, Institut National de la Santé et de la Recherche Médicale (INSERM), Ophtalmologie [Hôpital de la Timone - APMH], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'ophtalmologie [Rouen], Normandie Université (NU)-Hôpital Charles-Nicolle, Institut de Chimie des Substances Naturelles (ICSN), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Centre hospitalier universitaire de Nantes (CHU Nantes), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse, Université de Reims Champagne-Ardenne (URCA)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Hôpital Charles-Nicolle-CHU Rouen, Service de Virologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

المصدر: Antiviral Research
Antiviral Research, Elsevier Masson, 2017, 146, pp.205-212. ⟨10.1016/j.antiviral.2017.09.013⟩
Antiviral Research, 2017, 146, pp.205-212. ⟨10.1016/j.antiviral.2017.09.013⟩

مصطلحات موضوعية: Male, 0301 basic medicine, viruses, Acyclovir, Herpesvirus 1, Human, Drug resistance, medicine.disease_cause, Polymerase Chain Reaction, Gastroenterology, 0302 clinical medicine, Recurrence, Genotype, Prospective Studies, Child, media_common, Viral resistance, Valine, Middle Aged, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, 3. Good health, Child, Preschool, Valacyclovir, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, Herpes simplex keratitis, Adult, Drug, medicine.medical_specialty, Adolescent, media_common.quotation_subject, 030106 microbiology, Antiviral Agents, Virus, Keratitis, Young Adult, 03 medical and health sciences, Pharmacokinetics, Virology, Internal medicine, Drug Resistance, Viral, medicine, Humans, Dosing, Aged, Pharmacology, business.industry, Infant, Herpes Simplex, medicine.disease, Herpes simplex virus, Tears, Immunology, Keratitis, Herpetic, 030221 ophthalmology & optometry, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, business

الوصف: International audience; Recurrent herpes simplex keratitis (HSK) is a leading infectious cause of blindness in industrialized countries. Antiviral prophylaxis (AVP) may fail to prevent recurrence of HSK due to viral resistance, inadequate dosing, or poor patient compliance. In this prospective multicenter study, we enrolled immunocompetent patients with recurrent HSK despite AVP. Ocular samples were tested by PCR for herpes simplex virus 1 (HSV-1). HSV-1 drug resistance was assessed with a genotypic assay based on UL23 and UL30 gene sequencing. After curative full dose valacyclovir (VACV) treatment was started, peak and trough acyclovir (ACV) plasma concentrations were measured, and patient compliance to AVP was assessed with a questionnaire.The study sample was comprised of 43 patients. Six (14%) patients were positive for HSV-1 using PCR, of whom 5 (83%) harbored genotypically ACV-resistant (ACVR) virus, due to mutations in UL23 (n = 4) or UL30 (n = 1). Disease duration was statistically significantly longer in patients with viral resistance compared to other HSK patients [35.5 ± 23.4 years (range, 6.8–68.4 years) versus 11.1 ± 12.3 years (range, 0.8–56.3 year) respectively; Mann-Whitney p = 0.01)].While patients were treated with full dose VACV, trough ACV plasma concentrations were below the threshold for ACV sensitivity in 9.5% of cases, and compliance was poor in 5.3% of cases.To summarize, HSV-1 resistance to ACV seems to be a significant cause of failure of prophylaxis in patients with HSK and is associated with longer disease duration. Most PCR-positive samples contained genotypically ACVR virus and identification may aid in adapting treatment. Incomplete 24-h drug coverage may also explain some cases of failure of prophylaxis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d6c823d70c527ff3643c096544a92715Test
https://hal.archives-ouvertes.fr/hal-02316781Test

المؤلفون: Aurélie Maran-Gonzalez, Marian Gutowski, Pierre-Emmanuel Colombo, Marie Alexandre, William Jacot, Simon Thezenas, Marie Viala, Séverine Guiu, Gilles Romieu, Pierre-Jean Lamy

المساهمون: Institut du Cancer de Montpellier (ICM), Clinique Beau Soleil [Montpellier], Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)

المصدر: Breast Cancer Research and Treatment
Breast Cancer Research and Treatment, Springer Verlag, 2017, 165 (3), pp.611-621. ⟨10.1007/s10549-017-4373-7⟩

مصطلحات موضوعية: 0301 basic medicine, Oncology, Cancer Research, Receptor, ErbB-2, medicine.medical_treatment, [SDV]Life Sciences [q-bio], uPA/PAI-1, 0302 clinical medicine, Breast cancer, Recurrence, Antineoplastic Combined Chemotherapy Protocols, Aged, 80 and over, Middle Aged, Prognosis, 3. Good health, Treatment Outcome, Receptors, Estrogen, Chemotherapy, Adjuvant, 030220 oncology & carcinogenesis, Cohort, Biomarker (medicine), Female, Adjuvant, Adult, medicine.medical_specialty, Tailoring, Clinical Decision-Making, Breast Neoplasms, 03 medical and health sciences, Internal medicine, Plasminogen Activator Inhibitor 1, medicine, Biomarkers, Tumor, Humans, Pathological, Survival analysis, Aged, Neoplasm Staging, Gynecology, Chemotherapy, business.industry, Retrospective cohort study, medicine.disease, Survival Analysis, Urokinase-Type Plasminogen Activator, Adjuvant chemotherapy, 030104 developmental biology, Neoplasm Grading, business

الوصف: International audience; PURPOSE:Intermediate-risk early breast cancer (EBC) is a heterogeneous group in which adjuvant chemotherapy decision proves to be difficult. Clinical and pathological criteria are sometimes insufficient to determine the best therapeutic options, and validated biomarkers such as uPA/PAI-1, are needed to contribute to the decision-making. The objective of this study was to evaluate the clinical outcome of an unselected ER+/HER2- pN0 EBC cohort of patients in whom the routine clinical decision process included a prospective uPA/PAI-1 determination.METHOD:This monocentric retrospective study included 520 patients who underwent curative surgery in our institute between 2006 and 2011. Adjuvant therapeutic strategy was decided based on clinical-pathological data, altogether with a routine prospective determination of uPA/PAI-1 tumor levels using fresh, extemporaneously sampled tissue. We evaluated the correlation between uPA/PAI-1 levels, clinical-pathological variables, and the patient's outcome (relapse-free survival, RFS, and overall survival, OS).RESULT:Median follow-up was 5.4 years. The 5- and 10-year RFS rates were ,respectively, 95 and 89%, and the five-year OS rate was 96.3%. Forty percent of tumors had low uPA/PAI-1 levels. Seventy-five percent of patients with low uPA/PAI-1 levels did not receive chemotherapy, when 25% did. Sixty percent of patients with high uPA and/or PAI-1 levels received chemotherapy, while 40% did not. No statistical significant correlation was found between the uPA/PAI-1 levels and RFS or OS.CONCLUSION:The personalization of the patients' treatment using uPA/PAI-1 tumor levels allows the reversion of the well-known poor prognostic impact of high uPA/PAI-1 levels and strongly supports the use of this biomarker in clinical practice.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::a5aca09bbde8f675a5b80f21d4f1279dTest
https://hal.umontpellier.fr/hal-02430641Test

المؤلفون: Djamila Mezouar, Amel Saidi Merzouk, Michel Narce, Boumediene Belarbi, Hafida Merzouk, Sid Ahmed Merzouk

المساهمون: Laboratoire de physiologie, physiopathologie, biochimie de la nutrition (Université d'Aboubekr Belkaid Tlemcen), Université Aboubekr Belkaid - University of Belkaïd Abou Bekr [Tlemcen], Service de gynécologie-obstétrique (Etablissement spécialisé mère et enfant, Tlemcen, Algérie), Etablissement hospitalier spécialisé mère et enfant (Tlemcen, Algérie), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Algerian Health investigation Office (ATRSS PNR)

المصدر: Placenta
Placenta, Elsevier, 2016, 42, pp.114-21. 〈http://www.sciencedirect.com/science/article/pii/S0143400416300649Test〉. 〈10.1016/j.placenta.2016.04.013〉

مصطلحات موضوعية: 0301 basic medicine, Antioxidant, Glucose uptake, medicine.medical_treatment, Placenta, Proliferation, Pregnancy in Diabetics, Ascorbic Acid, medicine.disease_cause, Antioxidants, Fatty Acids, Monounsaturated, chemistry.chemical_compound, 0302 clinical medicine, Pregnancy, Malondialdehyde, Vitamin E, Vitamin C, [ SDV.MHEP.GEO ] Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, 030219 obstetrics & reproductive medicine, Trophoblast, Obstetrics and Gynecology, food and beverages, Catalase, medicine.anatomical_structure, Type 1 diabetes, [ SDV.BDLR ] Life Sciences [q-bio]/Reproductive Biology, Hypertension, Female, lipids (amino acids, peptides, and proteins), Oxidant/antioxidant status, Oxidation-Reduction, Intracellular, Polyunsaturated fatty-acids, Vitamin, Adult, Risk, medicine.medical_specialty, Placental cells, Biology, 03 medical and health sciences, Young Adult, Internal medicine, Fatty Acids, Omega-6, Fatty Acids, Omega-3, medicine, Humans, [ SDV.BDD ] Life Sciences [q-bio]/Development Biology, Cell Proliferation, Superoxide Dismutase, Mellitus, Preeclampsia, Diet, 030104 developmental biology, Endocrinology, Diabetes Mellitus, Type 1, Metabolism, Reproductive Medicine, chemistry, Oxidative stress, PUFA, Developmental Biology

الوصف: IF 2.972; International audience; The aim of this investigation was to determine the in vitro effects of vitamin C and E, n-3 and n-6 PUFA and n-9 MUFA on placental cell proliferation and function in type 1 diabetes. Placenta tissues were collected from 30 control healthy and 30 type 1 diabetic women at delivery. Placental cells were isolated and were cultured in RPMI medium supplemented with vitamin C (50 μM), vitamin E (50 μM), n-3 PUFA (100 μM), n-6 PUFA (100 μM) or n-9 MUFA (100 μM). Cell proliferation, cell glucose uptake and intracellular oxidative status were investigated. Our results showed that basal placental cell proliferation, glucose uptake, malondialdehyde (MDA) and carbonyl proteins were higher while intracellular reduced glutathione (GSH) levels and catalase activities were lower in placentas from diabetic women as compared to controls. Vitamins C and E induced a modulation of placental cell proliferation and glucose consumption without affecting intracellular redox status in both diabetic and control groups. N-3 and n-6 PUFA diminished placental cell proliferation and enhanced intracellular oxidative stress while n-9 MUFA had no effects in the two groups. Co-administration of n-3 or n-6 PUFA and vitamin C or E were capable of reversing back the PUFA-decreased cell proliferation and normalizing placental cell function and redox status especially in diabetes. In conclusion, PUFA and antioxidant vitamin combinations may be beneficial in improving placenta function and in reducing placental oxidative stress in type 1 diabetic pregnancy.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fc51a50907ea4df242540c4e93c7f47fTest
https://hal-univ-bourgogne.archives-ouvertes.fr/hal-01441076Test