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2,161 results on '"Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)"'

1. Biomarker counseling, disclosure of diagnosis and follow‐up in patients with mild cognitive impairment: A European Alzheimer's disease consortium survey

Author: Mathieu Ceccaldi, Timo Grimmer, Vesna Jelic, Luiza Spiru, Pierre Jean Ousset, Stephanie Sloan, Marcel G. M. Olde Rikkert, Isabel Santana, Sebastiaan Engelborghs, Bruno Dubois, Milica G. Kramberger, David Robinson, Lucrezia Hausner, Latchezar Traykov, Mercè Boada, Robert Perneczky, Gunhild Waldemar, Alberto Lleó, Elisabet Sánchez, Thomas R. Nielsen, Tomasz Gabryelewicz, Olivier Rouaud, Nikolaos Scarmeas, Alexandre de Mendonça, Jacques Hugon, Kristian Steen Frederiksen, Bernard Hanseeuw, Lutz Frölich, Flavio Nobili, Görsev Yener, Mario Riverol, Ildebrando Appollonio, Audrey Gabelle, Birgitte Bo Andersen, Elka Stefanova, Katerina Sheardova, Jakub Hort, Anne M Koivisto, Thibaud Lebouvier, Clinical sciences, Neuroprotection & Neuromodulation, Neurology, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service de neurologie, Frederiksen, K, Nielsen, T, Appollonio, I, Andersen, B, Riverol, M, Boada, M, Ceccaldi, M, Dubois, B, Engelborghs, S, Frolich, L, Hausner, L, Gabelle, A, Gabryelewicz, T, Grimmer, T, Hanseeuw, B, Hort, J, Hugon, J, Jelic, V, Koivisto, A, Kramberger, M, Lebouvier, T, Lleo, A, de Mendonca, A, Nobili, F, Ousset, P, Perneczky, R, Olde Rikkert, M, Robinson, D, Rouaud, O, Sanchez, E, Santana, I, Scarmeas, N, Sheardova, K, Sloan, S, Spiru, L, Stefanova, E, Traykov, L, Yener, G, Waldemar, G, University of Copenhagen = Københavns Universitet (UCPH), Università degli Studi di Milano-Bicocca = University of Milano-Bicocca (UNIMIB), Universidad Pública de Navarra [Espagne] = Public University of Navarra (UPNA), Universitat Internacional de Catalunya [Barcelona] (UIC), Instituto de Salud Carlos III [Madrid] (ISC), Institut de Neurosciences des Systèmes (INS), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital de la Timone [CHU - APHM] (TIMONE), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), University of Antwerp (UA), Vrije Universiteit Brussel (VUB), Heidelberg University, Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Mossakowski Medical Research Centre (CMDIK), Polska Akademia Nauk = Polish Academy of Sciences (PAN), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Université Catholique de Louvain = Catholic University of Louvain (UCL), University Hospital Motol [Prague], Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Cité (UPCité), Karolinska University Hospital [Stockholm], University of Eastern Finland, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, University of Ljubljana, Université de Lille, Hospital de la Santa Creu i Sant Pau, Universidade de Lisboa = University of Lisbon (ULISBOA), Università degli studi di Genova = University of Genoa (UniGe), IRCCS Ospedale Policlinico San Martino [Genoa, Italy], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Ludwig-Maximilians University [Munich] (LMU), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Munich Cluster for systems neurology [Munich] (SyNergy), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU), Imperial College London, Radboud University Medical Center [Nijmegen], St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Hospital Universitario Ramón y Cajal [Madrid], Universidad de Alcalá - University of Alcalá (UAH), University of Coimbra [Portugal] (UC), National and Kapodistrian University of Athens (NKUA), Columbia University Irving Medical Center (CUIMC), St. Anne’s University Hospital [Brno], Ninewells Hospital and Medical School [Dundee], University of Medicine and Pharmacy 'Carol Davila' Bucharest (UMPCD), University of Belgrade [Belgrade], and Dokuz Eylül Üniversitesi = Dokuz Eylül University [Izmir] (DEÜ)
Subjects: Counseling, Advance care planning, Alzheimer`s disease Donders Center for Medical Neuroscience [Radboudumc 1], diagnosis, Disease, 0302 clinical medicine, Medicine, 030212 general & internal medicine, survey experiment, Cognitive decline, Cognitive impairment, Response rate (survey), diagnosis [Alzheimer Disease], Alzheimer's disease, 3. Good health, Europe, diagnosi, Psychiatry and Mental health, Disease Progression, biomarker, Biomarker (medicine), biomarker counseling, biomarkers, dementia, diagnostic disclosure, mild cognitive impairment, survey, medicine.medical_specialty, Referral, Neuroscience(all), Clinical Neurology, Disclosure, Sensitivity and Specificity, 03 medical and health sciences, Alzheimer Disease, Humans, Dementia, Cognitive Dysfunction, ddc:610, MED/26 - NEUROLOGIA, business.industry, [SCCO.NEUR]Cognitive science/Neuroscience, medicine.disease, diagnosis [Cognitive Dysfunction], Family medicine, Human medicine, Geriatrics and Gerontology, business, Biomarkers, 030217 neurology & neurosurgery, Follow-Up Studies
Abstract: Contains fulltext : 231797.pdf (Publisher’s version ) (Closed access) OBJECTIVES: Mild cognitive impairment (MCI) is associated with an increased risk of further cognitive decline, partly depending on demographics and biomarker status. The aim of the present study was to survey the clinical practices of physicians in terms of biomarker counseling, management, and follow-up in European expert centers diagnosing patients with MCI. METHODS: An online email survey was distributed to physicians affiliated with European Alzheimer's disease Consortium centers (Northern Europe: 10 centers; Eastern and Central Europe: 9 centers; and Southern Europe: 15 centers) with questions on attitudes toward biomarkers and biomarker counseling in MCI and dementia. This included postbiomarker counseling and the process of diagnostic disclosure of MCI, as well as treatment and follow-up in MCI. RESULTS: The response rate for the survey was 80.9% (34 of 42 centers) across 20 countries. A large majority of physicians had access to biomarkers and found them useful. Pre- and postbiomarker counseling varied across centers, as did practices for referral to support groups and advice on preventive strategies. Less than half reported discussing driving and advance care planning with patients with MCI. CONCLUSIONS: The variability in clinical practices across centers calls for better biomarker counseling and better training to improve communication skills. Future initiatives should address the importance of communicating preventive strategies and advance planning.
Published: 2020

2. Intrinsic Differential Scanning Fluorimetry for Fast and Easy Identification of Adeno-Associated Virus Serotypes

Author: Martin Biel, Stylianos Michalakis, Gerhard Winter, Tim Menzen, Axel Rossi, Ruth Rieser, Eduard Ayuso, Hildegard Büning, Magalie Penaud-Budloo, Mohammed Bouzelha, Department of Pharmacy [Munich, Germany] (Center for Drug Research), Ludwig-Maximilians-Universität München (LMU), Laboratoire de Thérapie Génique Translationnelle des Maladies Génétiques (Inserm UMR 1089), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institute of Experimental Hematology [Hannover, Germany], Hannover Medical School [Hannover] (MHH), Coriolis Pharma [Martinsried, Germany], Center for Integrated Protein Science (CIPSM), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz-Zentrum München (HZM)-Ludwig Maximilian University of Munich [Germany] (LMU München), German Center for Infection Research - partner site Hannover-Braunschweig (DZIF), Department of Ophthalmology [Munich, Germany], This work was supported by the Deutsche Forschungsgemeinschaft (EXC114)., JAULIN, Nicolas, and Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU)-Helmholtz Zentrum München = German Research Center for Environmental Health
Subjects: Protein Denaturation, Time Factors, [SDV]Life Sciences [q-bio], viruses, Genetic enhancement, Pharmaceutical Science, adeno-associated virus, medicine.disease_cause, melting temperature, 030226 pharmacology & pharmacy, Virus, Workflow, law.invention, high-throughput technology, 03 medical and health sciences, Transduction (genetics), capsid thermal stability, 0302 clinical medicine, law, Gene expression, medicine, Transition Temperature, High throughput technology, Fluorometry, Adeno-associated virus, Fluorescent Dyes, Protein Unfolding, 030304 developmental biology, 0303 health sciences, Protein Stability, Chemistry, intrinsic fluorescence, Dependovirus, High-Throughput Screening Assays, Cell biology, [SDV] Life Sciences [q-bio], AAV vector, Capsid, Recombinant DNA, Capsid Proteins, Hydrophobic and Hydrophilic Interactions
Abstract: International audience; Recombinant adeno-associated virus (AAV) vectors have evolved as the most promising technology for gene therapy due to their good safety profile, high transduction efficacy, and long-term gene expression in non-dividing cells. AAV-based gene therapy holds great promise for treating genetic disorders like inherited blindness, muscular atrophy, or bleeding disorders. Multiple naturally occurring and engineered AAV serotypes exist, which differ in capsid sequence and as a consequence in cellular tropism. Individual AAV capsids differ in thermal stability and have a characteristic melting temperature (Tm), which enables serotype-specific discrimination of AAV vectors. Differential scanning fluorimetry (DSF) combined with a dye-like SYPRO Orange (SO-DSF), which binds to hydrophobic regions of unfolded proteins, has been successfully applied to determine the Tm of AAV capsids. Here, we present DSF measurement of intrinsic fluorescence signal (iDSF) as a simple alternative method for determination of AAV capsid Tm. The study demonstrates that DSF measurement of intrinsic fluorescence signal is a simple, accurate, and rapid alternative to SO-DSF, which enables characterization of AAV capsid stability with excellent precision and without the need of SO or any other dye.
Published: 2020

3. Inducers of the NF-κB pathways impair hepatitis delta virus replication and strongly decrease progeny infectivity

Author: Maud Michelet, Dulce Alfaiate, Brieux Chardès, Caroline Pons, Suzanne Faure-Dupuy, Thomas Engleitner, Rayan Farhat, Tobias Riedl, Anne-Flore Legrand, Roland Rad, Michel Rivoire, Fabien Zoulim, Mathias Heikenwälder, Anna Salvetti, David Durantel, Julie Lucifora, 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), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Département cancer environnement (Centre Léon Bérard - Lyon), Centre Léon Bérard [Lyon], International Center for Research in Infectiology, Lucifora, Julie, Institut des Agents Infectieux [Lyon] [IAI], Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] [TUM], Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] [DKFZ], Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Hepatitis B virus, Hepatology, viruses, lymphotoxin beta receptor, Gastroenterology, virus diseases, RC799-869, biochemical phenomena, metabolism, and nutrition, Diseases of the digestive system. Gastroenterology, NF-κB, Hepatitis D virus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Internal Medicine, toll-like receptor, Immunology and Allergy, hepatocytes
Abstract: Background & Aims: HDV superinfection of chronically HBV-infected patients is the most aggressive form of chronic viral hepatitis, with an accelerated progression towards fibrosis/cirrhosis and increased risk of liver failure, hepatocellular carcinoma, and death. While HDV infection is not susceptible to available direct anti-HBV drugs, suboptimal responses are obtained with interferon-α-based therapies, and the number of investigational drugs remains limited. We therefore analyzed the effect of several innate immune stimulators on HDV replication in infected hepatocytes. Methods: We used in vitro models of HDV and HBV infection based on primary human hepatocytes (PHHs) and the non-transformed HepaRG cell line that are relevant to explore new innate immune therapies. Results: We describe here, for the first time, anti-HDV effects of Pam3CSK4 and BS1, agonists of Toll-like receptor (TLR)-1/2, and the lymphotoxin-β receptor (LTβR), respectively. Both types of agonists induced dose-dependent reductions of total intracellular HDV genome and antigenome RNA and of HDV protein levels, without toxicity in cells monoinfected with HDV or co/superinfected with HBV. Moreover, both molecules negatively affected HDV progeny release and strongly decreased their specific infectivity. The latter effect is particularly important since HDV is thought to persist in humans through constant propagation. Conclusions: Immune-modulators inducing NF-κB pathways in hepatocytes can inhibit HDV replication and should be further evaluated as a possible therapeutic approach in chronically HBV/HDV-infected patients. Lay summary: Hepatitis delta virus causes the most severe form of viral hepatitis. Despite positive recent developments, effective treatments remain a major clinical need. Herein, we show that immune-modulators that trigger the NF-κB pathways could be effective for the treatment of hepatitis delta infections.
Published: 2021

4. CXCR6 deficiency impairs cancer vaccine efficacy and CD8+ resident memory T-cell recruitment in head and neck and lung tumors

Author: Karaki, Soumaya, Blanc, Charlotte, Tran, Thi, Galy-Fauroux, Isabelle, Mougel, Alice, Dransart, Estelle, Anson, Marie, Tanchot, Corinne, Paolini, Lea, Gruel, Nadege, Gibault, Laure, Lepimpec-Barhes, Francoise, Fabre, Elizabeth, Benhamouda, Nadine, Badoual, Cecile, Damotte, Diane, Donnadieu, Emmanuel, Kobold, Sebastian, Mami-Chouaib, Fathia, Golub, Rachel, Johannes, Ludger, Tartour, Eric, Vougny, Marie-Christine, Université Sorbonne Paris Cité - - USPC2011 - ANR-11-IDEX-0005 - IDEX - VALID, Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Equipe labellisée Ligue contre le Cancer, Chimie biologique des membranes et ciblage thérapeutique (CBMCT - UMR 3666 / U1143), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Recherche Translationnelle, Institut Curie [Paris], Service d’anatomo‑pathologie [AP-HP Hôpital Européen Georges Pompidou] (Centre de Ressources biologiques), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Center for Integrated Protein Science (CIPSM), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU)-Helmholtz Zentrum München = German Research Center for Environmental Health, German Center for Lung Research - DZL [Munich, Germany], Immunologie intégrative des tumeurs et immunothérapie des cancers (INTIM), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Lymphopoïèse (Lymphopoïèse (UMR_1223 / U1223 / U-Pasteur_4)), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), This work has been funded by Fondation ARC, INCA PLBio, Labex Immuno-Oncology, Site intégré de recherche en cancérologie (SIRIC CARPEM, SIRIC Curie), Cancéropole d’Ile de France, Carnot Curie Cancer, FONCER. SK is supported by the European Research Council (grant 756017, ARMOR-T)., ANR-11-IDEX-0005,USPC,Université Sorbonne Paris Cité(2011), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC), Département de recherche translationnelle, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz-Zentrum München (HZM)-Ludwig Maximilian University of Munich [Germany] (LMU München), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), École Pratique des Hautes Études (EPHE), and Technical University of Munich (TUM)-Ludwig Maximilian University of Munich [Germany] (LMU München)-Helmholtz-Zentrum München (HZM)
Subjects: Lung Neoplasms, [SDV.IMM] Life Sciences [q-bio]/Immunology, Vaccine Efficacy, immunization, Cancer Vaccines, Memory T Cells, Lymphocytes, Tumor-Infiltrating, Cell Line, Tumor, Tumor Microenvironment, Animals, Humans, Administration, Intranasal, RC254-282, Receptors, CXCR6, Mice, Knockout, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Basic Tumor Immunology, Chemokine CXCL16, adaptive immunity, vaccination, Tumor Burden, Mice, Inbred C57BL, Phenotype, Head and Neck Neoplasms, CD8-positive T-lymphocytes, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Immunologic Memory
Abstract: International audience; Background Resident memory T lymphocytes (TRM) are located in tissues and play an important role in immunosurveillance against tumors. The presence of TRM prior to treatment or their induction is associated to the response to anti-Programmed cell death protein 1 (PD-1)/Programmed death-ligand 1 (PD-L1) immunotherapy and the efficacy of cancer vaccines. Previous work by our group and others has shown that the intranasal route of vaccination allows more efficient induction of these cells in head and neck and lung mucosa, resulting in better tumor protection. The mechanisms of in vivo migration of these cells remains largely unknown, apart from the fact that they express the chemokine receptor CXCR6.Methods We used CXCR6-deficient mice and an intranasal tumor vaccination model targeting the Human Papillomavirus (HPV) E7 protein expressed by the TC-1 lung cancer epithelial cell line. The role of CXCR6 and its ligand, CXCL16, was analyzed using multiparametric cytometric techniques and Luminex assays.Human biopsies obtained from patients with lung cancer were also included in this study.Results We showed that CXCR6 was preferentially expressed by CD8+ TRM after vaccination in mice and also on intratumoral CD8+ TRM derived from human lung cancer. We also demonstrate that vaccination of Cxcr6-deficient mice induces a defect in the lung recruitment of antigen-specific CD8+ T cells, preferentially in the TRM subsets. In addition, we found that intranasal vaccination with a cancer vaccine is less effective in these Cxcr6-deficient mice compared with wild-type mice, and this loss of efficacy is associated with decreased recruitment of local antitumor CD8+ TRM. Interestingly, intranasal, but not intramuscular vaccination induced higher and more sustained concentrations of CXCL16, compared with other chemokines, in the bronchoalveolar lavage fluid and pulmonary parenchyma.Conclusions This work demonstrates the in vivo role of CXCR6-CXCL16 axis in the migration of CD8+ resident memory T cells in lung mucosa after vaccination, resulting in the control of tumor growth. This work reinforces and explains why the intranasal route of vaccination is the most appropriate strategy for inducing these cells in the head and neck and pulmonary mucosa, which remains a major objective to overcome resistance to anti-PD-1/PD-L1, especially in cold tumors.
Published: 2021

5. Mouse mutant phenotyping at scale reveals novel genes controlling bone mineral density

Author: Paul Flicek, Raffaele Teperino, Lydia Teboul, Thomas Werner, Marie-France Champy, Christopher J. Lelliott, Graham R. Williams, Jacqueline K. White, Gregor Miller, Mary E. Dickinson, Ann M Flenniken, Radislav Sedlacek, Martin Hrabé de Angelis, John R. Seavitt, Peter I. Croucher, Maria del Mar Muniz Moreno, Sara Wells, Jan Rozman, Terrence F. Meehan, Kristian F Odfalk, Juan Gallegos, J. H. Duncan Bassett, Mohammed Selloum, John G. Logan, Sylvie Jacquot, Elena J. Ghirardello, Robert Braun, Frantisek Spoutil, Kevin C K Lloyd, Lore Becker, Stephen A. Murray, Jan Prochazka, Elif F. Acar, Taylor S Vales, Michelle Simon, Helmut Fuchs, Nadine Spielmann, Mark Griffiths, Piia Keskivali-Bond, Valerie Gailus-Durner, Tania Sorg, Christine Schütt, Jeremy Mason, Helen Parkinson, Karen L. Svenson, Abdel Ayadi, Anna L Swan, Jason D. Heaney, Colin McKerlie, Wolfgang Wurst, Ann-Marie Mallon, Heather Cater, Stefanie Leuchtenberger, Harald Grallert, Steve D.M. Brown, Stefan Brandmaier, Yann Herault, Philipp Mayer-Kuckuk, Corey L. Reynolds, Ala Moshiri, Robert Brommage, Derek D. Cissell, Lauryl M J Nutter, Connor Lally, MRC Harwell Institute [UK], German Research Center for Environmental Health - Helmholtz Center München (GmbH), German Center for Diabetes Research - Deutsches Zentrum für Diabetesforschung [Neuherberg] (DZD), Institute of Molecular Genetics of the Czech Academy of Sciences (IMG / CAS), Czech Academy of Sciences [Prague] (CAS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Helmholtz-Zentrum München (HZM), The Wellcome Trust Sanger Institute [Cambridge], University of Michigan [Ann Arbor], University of Michigan System, University of California [Davis] (UC Davis), University of California, Baylor College of Medicine (BCM), Baylor University, European Molecular Biology Laboratory [Hinxton], University of Toronto, University of Manitoba [Winnipeg], Lunenfeld-Tanenbaum Research Institute [Toronto, Canada], French National Infrastructure for Mouse Phenogenomics (PHENOMIN), The Jackson Laboratory [Bar Harbor] (JAX), European Bioinformatics Institute [Hinxton] (EMBL-EBI), EMBL Heidelberg, Imperial College London, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Deutsches Zentrum für Neurodegenerative Erkrankungen [Ulm] (DZNE), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Munich Cluster for systems neurology [Munich] (SyNergy), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU), Garvan Institute of Medical Research [Sydney, Australia], St. Vincent’s Clinical School [Sydney, Australia], UNSW Faculty of Medicine [Sydney], University of New South Wales [Sydney] (UNSW)-University of New South Wales [Sydney] (UNSW), Université de Nouvelle-Galles du Sud - UNSW [Sydney, Australia], Mundlos, Stefan, Wellcome Trust, Commission of the European Communities, European Commission, Herault, Yann, Helmholtz Zentrum München = German Research Center for Environmental Health, University of California (UC), Garvan Institute of medical research, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Technische Universität München [München] (TUM), Technische Universität München [München] (TUM)-Ludwig-Maximilians-Universität München (LMU), Swan, Anna L [0000-0003-1810-3756], Rozman, Jan [0000-0002-8035-8904], Del Mar Muñiz Moreno, Maria [0000-0002-2662-890X], Leuchtenberger, Stefanie [0000-0003-2475-0810], Brommage, Robert [0000-0002-9947-3822], Grallert, Harald [0000-0002-6876-9655], Werner, Thomas [0000-0003-0402-4539], Teperino, Raffaele [0000-0001-8815-1409], Becker, Lore [0000-0002-6890-4984], Miller, Gregor [0000-0002-4281-4905], Seavitt, John R [0000-0003-3209-3187], Cissell, Derek D [0000-0002-6450-422X], Acar, Elif F [0000-0003-2908-7691], Lelliott, Christopher J [0000-0001-8087-4530], Braun, Robert E [0000-0003-3856-9465], Cater, Heather [0000-0002-8696-6070], Flicek, Paul [0000-0002-3897-7955], Ghirardello, Elena J [0000-0002-1100-9217], Heaney, Jason D [0000-0001-8475-8828], Lally, Connor [0000-0002-3801-1966], Logan, John G [0000-0003-2801-700X], Mason, Jeremy [0000-0002-2796-5123], Nutter, Lauryl MJ [0000-0001-9619-146X], Odfalk, Kristian F [0000-0003-4152-4583], Prochazka, Jan [0000-0003-4675-8995], Selloum, Mohammed [0000-0003-4057-3519], Spoutil, Frantisek [0000-0002-7310-3487], Svenson, Karen L [0000-0002-7928-1911], Vales, Taylor S [0000-0001-9751-5681], Wells, Sara E [0000-0002-0572-0600], White, Jacqueline K [0000-0001-6268-2826], Sedlacek, Radislav [0000-0002-3352-392X], Wurst, Wolfgang [0000-0003-4422-7410], Lloyd, KC Kent [0000-0002-5318-4144], Williams, Graham R [0000-0002-8555-8219], Herault, Yann [0000-0001-7049-6900], Brown, Steve DM [0000-0002-0617-4824], Hrabe de Angelis, Martin [0000-0002-7898-2353], and Apollo - University of Cambridge Repository
Subjects: Male, Osteoporosis, genetics [Gene Expression Regulation], Transgenic, Transcriptome, Mice, 0302 clinical medicine, Animal Cells, Aetiology, Musculoskeletal System, Connective Tissue Cells, Genetics & Heredity, 0303 health sciences, Genomics, 3. Good health, Cellular Types, musculoskeletal diseases, Genotype, In silico, 1.1 Normal biological development and functioning, 03 medical and health sciences, genetics [Osteoporosis], Rheumatology, pathology [Osteoblasts], Genetic, Genome-Wide Association Studies, Genetics, GENOME-WIDE ASSOCIATION, Molecular Biology, Skeleton, Ecology, Evolution, Behavior and Systematics, METAANALYSIS, metabolism [Osteoblasts], 0604 Genetics, [SDV.GEN]Life Sciences [q-bio]/Genetics, Science & Technology, Osteoblasts, IDENTIFICATION, Biology and Life Sciences, Computational Biology, medicine.disease, COLLAGEN, Biological Tissue, OSTEOGENESIS IMPERFECTA, DISCOVERY, IMPC Consortium, Mutation, Animal Studies, Developmental Biology, Candidate gene, Cancer Research, Bone density, Gene Expression, Osteoclasts, [SDV.GEN] Life Sciences [q-bio]/Genetics, QH426-470, Bone remodeling, Bone Density, Medicine and Health Sciences, 2.1 Biological and endogenous factors, Protein Interaction Maps, Connective Tissue Diseases, Promoter Regions, Genetic, Genetics (clinical), Bone mineral, Sex Characteristics, genetics [Bone Density], metabolism [Osteoclasts], Genetic Pleiotropy, Animal Models, pathology [Osteoclasts], Phenotype, DIFFERENTIATION, Experimental Organism Systems, ANIMAL-MODELS, Connective Tissue, SEX, Female, Anatomy, Technology Platforms, Life Sciences & Biomedicine, Research Article, metabolism [Osteoporosis], Mouse Models, 030209 endocrinology & metabolism, Mice, Transgenic, Biology, Research and Analysis Methods, Promoter Regions, Model Organisms, Underpinning research, medicine, Animals, ddc:610, Bone, 030304 developmental biology, Human Genetics, Cell Biology, Genome Analysis, Gene Ontology, Gene Expression Regulation, Musculoskeletal, Genome-Wide Association Study
Abstract: The genetic landscape of diseases associated with changes in bone mineral density (BMD), such as osteoporosis, is only partially understood. Here, we explored data from 3,823 mutant mouse strains for BMD, a measure that is frequently altered in a range of bone pathologies, including osteoporosis. A total of 200 genes were found to significantly affect BMD. This pool of BMD genes comprised 141 genes with previously unknown functions in bone biology and was complementary to pools derived from recent human studies. Nineteen of the 141 genes also caused skeletal abnormalities. Examination of the BMD genes in osteoclasts and osteoblasts underscored BMD pathways, including vesicle transport, in these cells and together with in silico bone turnover studies resulted in the prioritization of candidate genes for further investigation. Overall, the results add novel pathophysiological and molecular insight into bone health and disease., Author summary Patients affected by osteoporosis frequently present with decreased BMD and increased fracture risk. Genes are known to control the onset and progression of bone diseases such as osteoporosis. Therefore, we aimed to identify osteoporosis-related genes using BMD measures obtained from a large pool of mutant mice genetically modified for deletion of individual genes (knockout mice). In a collaborative endeavor involving several research sites world-wide, we generated and phenotyped 3,823 knockout mice and identified 200 genes which regulated BMD. Of the 200 BMD genes, 141 genes were previously not known to affect BMD. The discovery and study of novel BMD genes will help to better understand the causes and therapeutic options for patients with low BMD. In the long run, this will improve the clinical management of osteoporosis.
Published: 2021
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6. Genome-wide association study reveals new insights into the heritability and genetic correlates of developmental dyslexia

Author: Daniel Brandeis, Nazanin Mirza-Schreiber, Bruce F. Pennington, Shelley D. Smith, Guillaume Huguet, Milene Bonte, Franck Ramus, Valéria Csépe, Till F. M. Andlauer, Silvia Paracchini, Arndt Wilcke, Paavo H.T. Leppänen, Dénes Tóth, Markus M. Nöthen, Heikki Lyytinen, Jessica Becker, Thomas Bourgeron, Jacqueline Hulslander, Simon E. Fisher, Karin Landerl, Richard K. Olson, Bertram Müller-Myhsok, Fabien Fauchereau, Yves Chaix, Stéphanie Iannuzzi, Juha Kere, Jean-François Démonet, Darina Czamara, Anniek Vaessen, Beate St Pourcain, Andrew P. Morris, Clyde Francks, Per Hoffmann, Myriam Peyrard-Janvid, Ferenc Honbolygó, John C. DeFries, Urs Maurer, John F. Stein, Thomas S. Scerri, Holger Kirsten, Joel B. Talcott, Gerd Schulte-Körne, Anthony P. Monaco, Alessandro Gialluisi, Erik G. Willcutt, Kerstin U. Ludwig, Bent Müller, Kristina Moll, Johannes Schumacher, STEMM - Stem Cells and Metabolism Research Program, Juha Kere / Principal Investigator, Research Programs Unit, University of Helsinki, Language, RS: FPN CN 7, Max-Planck-Institut für Psychiatrie, Max-Planck-Gesellschaft, Munich Cluster for systems neurology [Munich] (SyNergy), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU), Istituto Neurologico Mediterraneo (NEUROMED I.R.C.C.S.), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome]-Università degli studi di Napoli Federico II, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Helmholtz-Zentrum München (HZM), Ludwig-Maximilians-Universität München (LMU), University of Bonn, Max Planck Institute for Psycholinguistics, Radboud university [Nijmegen], University of Bristol [Bristol], Hungarian Academy of Sciences (MTA), Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Toulouse Neuro Imaging Center (ToNIC), 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)-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Université de Lausanne (UNIL), University of Liverpool, University of Manchester [Manchester], University of Oxford [Oxford], University of Colorado [Boulder], University of Nebraska Medical Center, University of Nebraska System, University of Denver, Maastricht University [Maastricht], The Chinese University of Hong Kong [Hong Kong], University of Jyväskylä (JYU), Karolinska Institutet [Stockholm], Universität Zürich [Zürich] = University of Zurich (UZH), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Universität Heidelberg [Heidelberg], Aston University [Birmingham], Fraunhofer Institute for Cell Therapy and Immunology (Fraunhofer IZI), Fraunhofer (Fraunhofer-Gesellschaft), Universität Leipzig [Leipzig], Tufts University [Medford], Laboratoire de sciences cognitives et psycholinguistique (LSCP), Département d'Etudes Cognitives - ENS Paris (DEC), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS), BioTechMed-Graz, Graz University of Technology [Graz] (TU Graz)-University of Graz-Medical University Graz, University of Melbourne, University of St Andrews [Scotland], AG and TFMA were supported by the Munich Cluster for Systems Neurology (SyNergy). AG was supported by Fondazione Umberto Veronesi. SP is a Royal Society University Research fellow. BMM, CF, BSP and SEF are supported by the Max Planck Society. AW, BM and HK were funded by the Fraunhofer Society and the Max Planck Society within the 'Pakt für Forschung und Innovation'. HK was also supported by LIFE—Leipzig Research Center for Civilization Diseases funded by means of the European Union, the European Regional Development Fund (ERDF), and the Free State of Saxony within the excellence initiative. FR is supported by Agence Nationale de la Recherche (ANR-06-NEURO-019-01, ANR-17-EURE-0017 IEC, ANR-10-IDEX-0001-02 PSL, ANR-11-BSV4-014-01), European Commission (LSHM-CT-2005-018696). TFMA was supported by the B.M.B.F. through the DIFUTURE consortium of the Medical Informatics Initiative Germany (grant 01ZZ1804A) and by the European Union’s Horizon 2020 Research and Innovation Programme (grant MultipleMS, EU RIA 733161)., ANR-06-NEUR-0019,GENEDYS,Origines cognitives, neurologiques et génétiques des troubles développementaux du langage(2006), ANR-17-EURE-0017,FrontCog,Frontières en cognition(2017), ANR-10-IDEX-0001,PSL,Paris Sciences et Lettres(2010), ANR-11-BSV4-0014,DYSBRAIN,Le cerveau dyslexique(2011), Graz University of Technology [Graz] (TU Graz)-Medical University Graz-Karl-Franzens-Universität [Graz, Autriche], Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA)-University of Naples Federico II = Università degli studi di Napoli Federico II, Helmholtz Zentrum München = German Research Center for Environmental Health, Universität Bonn = University of Bonn, Radboud University [Nijmegen], Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Toulouse Mind & Brain Institut (TMBI), Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Lausanne = University of Lausanne (UNIL), University of Oxford, Universität Heidelberg [Heidelberg] = Heidelberg University, Universität Leipzig, École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS-PSL), Graz University of Technology [Graz] (TU Graz)-Karl-Franzens-Universität Graz-Medical University Graz, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, The Royal Society, University of St Andrews. School of Medicine, University of St Andrews. Centre for Biophotonics, University of St Andrews. Biomedical Sciences Research Complex, and University of St Andrews. Cellular Medicine Division
Subjects: Multifactorial Inheritance, Intelligence, LANGUAGE, Genome-wide association study, INTELLIGENCE, Educational attaintment, 3124 Neurology and psychiatry, Dyslexia, READING-DISABILITY, MOLECULAR-GENETICS, 0302 clinical medicine, SCHIZOPHRENIA, GWAS, Brain cortical thickness, Genetics, 0303 health sciences, Intracellular Signaling Peptides and Proteins, [SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences, 3. Good health, ddc, Psychiatry and Mental health, SUSCEPTIBILITY GENE, Schizophrenia, BDC, RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry, Neuroinformatics, Reading disability, Bipolar disorder, Developmental dyslexia, NDAS, QH426 Genetics, Biology, Polymorphism, Single Nucleotide, INDIVIDUAL-DIFFERENCES, Article, Heritability, 03 medical and health sciences, Cellular and Molecular Neuroscience, AGE, medicine, LOCUS, Attention deficit hyperactivity disorder, SNP, ADHD, Humans, Genetic Predisposition to Disease, Molecular Biology, QH426, 030304 developmental biology, Polygenic risk, medicine.disease, Transverse temporal gyrus, Reading, Attention Deficit Disorder with Hyperactivity, RC0321, Psychiatric disorders, COMORBIDITY, 030217 neurology & neurosurgery, Neuroscience, Genome-Wide Association Study
Abstract: Funding: AG and TFMA were supported by the Munich Cluster for Systems Neurology (SyNergy). AG 535 was supported by Fondazione Umberto Veronesi. SP is a Royal Society University Research fellow. BMM, CF, BSP and SEF are supported by the Max Planck Society. AW, BM and HK were funded by the Fraunhofer Society and the Max Planck Society within the ‘Pakt für Forschung und Innovation’. HK was also supported by LIFE – Leipzig Research Center for Civilization Diseases funded by means of the European Union; the European Regional Development Fund (ERDF); and the Free State of Saxony within the excellence initiative. FR is supported by Agence Nationale de la Recherche (ANR-06-NEURO-019-01, ANR-17-EURE-542 0017 IEC, ANR-10-IDEX-0001-02 PSL, ANR-11-BSV4-014-01), European Commission (LSHM-CT-2005-018696). TFMA was supported by the BMBF through the DIFUTURE consortium of the Medical Informatics Initiative Germany (grant 01ZZ1804A) and by the European Union’s Horizon 2020 Research and Innovation Programme (grant MultipleMS, EU RIA 733161). Developmental dyslexia (DD) is a learning disorder affecting the ability to read, with a heritability of 40–60%. A notable part of this heritability remains unexplained, and large genetic studies are warranted to identify new susceptibility genes and clarify the genetic bases of dyslexia. We carried out a genome-wide association study (GWAS) on 2274 dyslexia cases and 6272 controls, testing associations at the single variant, gene, and pathway level, and estimating heritability using single-nucleotide polymorphism (SNP) data. We also calculated polygenic scores (PGSs) based on large-scale GWAS data for different neuropsychiatric disorders and cortical brain measures, educational attainment, and fluid intelligence, testing them for association with dyslexia status in our sample. We observed statistically significant (p
Published: 2021

7. Biallelic AOPEP Loss‐of‐Function Variants Cause Progressive Dystonia with Prominent Limb Involvement

Author: Aurélie Méneret, Manju A. Kurian, Michael C. Kruer, Alexander P. Drew, Niccolo E. Mencacci, Jean Madeleine de Sainte Agathe, Juliane Winkelmann, Lisa G. Riley, Sylvia Boesch, Saskia Biskup, Pedro Gonzalez-Alegre, Sheng Chih Jin, Janine Reunert, Sophie Reining, Kishore R. Kumar, Matthias Baumann, Riccardo Berutti, Fabienne Clot, Marie Vidailhet, Victor S.C. Fung, Thorsten Marquardt, Steven J. Lubbe, Robert Adam, Somayeh Bakhtiari, Tanya Bardakjian, Nicolas Derive, Ignacio Juan Keller Sarmiento, Michel Tchan, Michael Zech, Helmholtz Zentrum München = German Research Center for Environmental Health, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Concord Repatriation General Hospital, The University of Sydney, Garvan Institute of medical research, University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), Westmead Hospital [Sydney], Royal Brisbane & Women's Hospital, University of Queensland [Brisbane], Centre for Clinical Research [Brisbane], CeGaT GmbH, Barrow Neurological Institute, University of Arizona, Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Perelman School of Medicine, University of Pennsylvania, Northwestern University Feinberg School of Medicine, Institute of Child Health [London], University College of London [London] (UCL), Great Ormond Street Hospital for Children [London] (GOSH), Unité fonctionnelle de neurogénétique moléculaire et cellulaire, 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), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-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)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Munich Cluster for systems neurology [Munich] (SyNergy), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU), Gestionnaire, Hal Sorbonne Université, Helmholtz-Zentrum München (HZM), Technische Universität München [München] (TUM), Garvan Institute of Medical Research [Darlinghurst, Australia], University of Pennsylvania [Philadelphia], Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Innsbruck Medical University [Austria] (IMU), and Technische Universität München [München] (TUM)-Ludwig-Maximilians-Universität München (LMU)
Subjects: Proband, Movement disorders, AOPEP, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, rare disease, Biology, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Compound heterozygosity, loss-of-function variants, Aminopeptidases, Aopep, Genomic Analysis, Loss-of-function Variants, Monogenic Dystonia, Rare Disease, Frameshift mutation, 03 medical and health sciences, 0302 clinical medicine, Loss of Function Mutation, medicine, Humans, Exome, Allele, 030304 developmental biology, Dystonia, Genetics, 0303 health sciences, Parkinsonism, Proteolytic enzymes, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, medicine.disease, Pedigree, Phenotype, Neurology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Dystonic Disorders, genomic analysis, Mutation, Neurology (clinical), medicine.symptom, 030217 neurology & neurosurgery, monogenic dystonia
Abstract: BACKGROUND Monogenic causes of isolated dystonia are heterogeneous. Assembling cohorts of affected individuals sufficiently large to establish new gene-disease relationships can be challenging. OBJECTIVE We sought to expand the catalogue of monogenic etiologies for isolated dystonia. METHODS After the discovery of a candidate variant in a multicenter exome-sequenced cohort of affected individuals with dystonia, we queried online platforms and genomic data repositories worldwide to identify subjects with matching genotypic profiles. RESULTS Seven different biallelic loss-of-function variants in AOPEP were detected in five probands from four unrelated families with strongly overlapping phenotypes. In one proband, we observed a homozygous nonsense variant (c.1477C>T [p.Arg493*]). A second proband harbored compound heterozygous nonsense variants (c.763C>T [p.Arg255*]; c.777G>A [p.Trp259*]), whereas a third proband possessed a frameshift variant (c.696_697delAG [p.Ala234Serfs*5]) in trans with a splice-disrupting alteration (c.2041-1G>A). Two probands (siblings) from a fourth family shared compound heterozygous frameshift alleles (c.1215delT [p.Val406Cysfs*14]; c.1744delA [p.Met582Cysfs*6]). All variants were rare and expected to result in truncated proteins devoid of functionally important amino acid sequence. AOPEP, widely expressed in developing and adult human brain, encodes a zinc-dependent aminopeptidase, a member of a class of proteolytic enzymes implicated in synaptogenesis and neural maintenance. The probands presented with disabling progressive dystonia predominantly affecting upper and lower extremities, with variable involvement of craniocervical muscles. Dystonia was unaccompanied by any additional symptoms in three families, whereas the fourth family presented co-occurring late-onset parkinsonism. CONCLUSIONS Our findings suggest a likely causative role of predicted inactivating biallelic AOPEP variants in cases of autosomal recessive dystonia. Additional studies are warranted to understand the pathophysiology associated with loss-of-function variation in AOPEP. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Published: 2021

8. Type 2 diabetes risk gene Dusp8 regulates hypothalamic Jnk signaling and insulin sensitivity

Author: Florian Giesert, Dhiraj G. Kabra, Timo D. Müller, Kerstin Stemmer, Meri De Angelis, Martin Hrabé de Angelis, Fabian Seebacher, Martin Heni, Sonja C. Schriever, Ruchi Jain, Luke Harrison, Moya Wu, Martin Irmler, Rubén Nogueiras, Johannes Beckers, Hans-Ulrich Häring, Serge Luquet, Stephanie Kullmann, Chun-Xia Yi, Natalie Krahmer, Felipe Correa-da-Silva, Emily Violette Baumgart, Julien Castel, Paul T. Pfluger, Sarah Martinez, Peter Baumann, Mathias V. Schmidt, Jeffery D. Molkentin, Katrin Pfuhlmann, Hannah Schug, Jan Rozman, Wolfgang Wurst, Joachim Nagler, Matthias H. Tschöp, Helmholtz-Zentrum München (HZM), German Center for Diabetes Research - Deutsches Zentrum für Diabetesforschung [Neuherberg] (DZD), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Institute for Diabetes Research and Metabolic Diseases [Tübingen, Germany], VU University Medical Center [Amsterdam], Netherlands Institute for Neuroscience (NIN), Royal Netherlands Academy of Arts and Sciences (KNAW), TUM School of Life Sciences Weihenstephan, Skane University Hospital [Malmo], Lund University [Lund], Synlab [Lausanne], Unité de Biologie Fonctionnelle et Adaptative (BFA (UMR_8251 / U1133)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), School Life Science Weihenstephan (TUM), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Munich Cluster for systems neurology [Munich] (SyNergy), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU), Institute of Molecular Genetics of the Czech Academy of Sciences (IMG / CAS), Czech Academy of Sciences [Prague] (CAS), Howard Hughes Medical Institute (HHMI), Cincinnati Children's Hospital Medical Center, Institute of the Royal Netherlands Academy of Arts and Sciences, Max Planck Institute of Psychiatry, Max-Planck-Gesellschaft, Endocrinology, Laboratory for Endocrinology, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, and Amsterdam Gastroenterology Endocrinology Metabolism
Subjects: 0301 basic medicine, MAP Kinase Kinase 4, [SDV]Life Sciences [q-bio], Type 2 diabetes, Mice, chemistry.chemical_compound, 0302 clinical medicine, Corticosterone, enzymology [Hypothalamus], Glucose homeostasis, genetics [Diabetes Mellitus, Experimental], Mice, Knockout, Kinase, Diabetes, enzymology [Diabetes Mellitus, Experimental], General Medicine, metabolism [Dual-Specificity Phosphatases], DUSP8 protein, mouse, 030220 oncology & carcinogenesis, Dual-Specificity Phosphatases, medicine.symptom, Signal Transduction, medicine.medical_specialty, Hypothalamus, enzymology [Diabetes Mellitus, Type 2], Inflammation, genetics [Diabetes Mellitus, Type 2], Diabetes Mellitus, Experimental, 03 medical and health sciences, Insulin resistance, Commentaries, Internal medicine, Diabetes mellitus, medicine, Animals, genetics [MAP Kinase Kinase 4], ddc:610, Obesity, genetics [Dual-Specificity Phosphatases], business.industry, metabolism [MAP Kinase Kinase 4], medicine.disease, 030104 developmental biology, Endocrinology, Metabolism, Diabetes Mellitus, Type 2, chemistry, Commentary, Insulin Resistance, business, Hormone
Abstract: International audience; Recent genome-wide association studies (GWAS) identified DUSP8, encoding a dual-specificity phosphatase targeting mitogen-activated protein kinases, as a type 2 diabetes (T2D) risk gene. Here, we reveal that Dusp8 is a gatekeeper in the hypothalamic control of glucose homeostasis in mice and humans. Male, but not female, Dusp8 loss-of-function mice, either with global or corticotropin-releasing hormone neuron-specific deletion, had impaired systemic glucose tolerance and insulin sensitivity when exposed to high-fat diet (HFD). Mechanistically, we found impaired hypothalamic-pituitary-adrenal axis feedback, blunted sympathetic responsiveness, and chronically elevated corticosterone levels driven by hypothalamic hyperactivation of Jnk signaling. Accordingly, global Jnk1 ablation, AAV-mediated Dusp8 overexpression in the mediobasal hypothalamus, or metyrapone-induced chemical adrenalectomy rescued the impaired glucose homeostasis of obese male Dusp8-KO mice, respectively. The sex-specific role of murine Dusp8 in governing hypothalamic Jnk signaling, insulin sensitivity, and systemic glucose tolerance was consistent with functional MRI data in human volunteers that revealed an association of the DUSP8 rs2334499 risk variant with hypothalamic insulin resistance in men. Further, expression of DUSP8 was increased in the infundibular nucleus of T2D humans. In summary, our findings suggest the GWAS-identified gene Dusp8 as a novel hypothalamic factor that plays a functional role in the etiology of T2D.
Published: 2020

9. Myelin replacement triggered by single-cell demyelination in mouse cortex

Author: Snaidero, Nicolas, Schifferer, Martina, Mezydlo, Aleksandra, Zalc, Bernard, Kerschensteiner, Martin, Misgeld, Thomas, Biomedical Center = Biomedizinisches centrum [Munich, Germany] (BMC), Ludwig-Maximilians-Universität München (LMU), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Munich Cluster for systems neurology [Munich] (SyNergy), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU), Institute of Clinical Neuroimmunology [Munich, Germany], Ludwig-Maximilians University [Munich] (LMU), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), 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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Gestionnaire, HAL Sorbonne Université 5, Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, metabolism [Myelin Sheath], Science, Myelin biology and repair, [SDV]Life Sciences [q-bio], metabolism [Axons], Article, cytology [Cerebral Cortex], metabolism [Oligodendroglia], Mice, Animals, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], lcsh:Science, cytology [Oligodendroglia], Myelin Sheath, Cerebral Cortex, metabolism [Cerebral Cortex], Oligodendrocyte, Axons, [SDV] Life Sciences [q-bio], Mice, Inbred C57BL, Oligodendroglia, Remyelination, nervous system, lcsh:Q, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], ddc:500
Abstract: Myelin, rather than being a static insulator of axons, is emerging as an active participant in circuit plasticity. This requires precise regulation of oligodendrocyte numbers and myelination patterns. Here, by devising a laser ablation approach of single oligodendrocytes, followed by in vivo imaging and correlated ultrastructural reconstructions, we report that in mouse cortex demyelination as subtle as the loss of a single oligodendrocyte can trigger robust cell replacement and remyelination timed by myelin breakdown. This results in reliable reestablishment of the original myelin pattern along continuously myelinated axons, while in parallel, patchy isolated internodes emerge on previously unmyelinated axons. Therefore, in mammalian cortex, internodes along partially myelinated cortical axons are typically not reestablished, suggesting that the cues that guide patchy myelination are not preserved through cycles of de- and remyelination. In contrast, myelin sheaths forming continuous patterns show remarkable homeostatic resilience and remyelinate with single axon precision., Myelination is a highly regulated phenomenon. Here, the authors show that demyelination induced by the loss of a single oligodendrocyte triggers replenishment of a specific fraction the original myelin and myelination of previously unmyelinated axons in the mouse cortex.
Published: 2020

10. Photoinduced water oxidation in pyrimidine-water clusters: a combined experimental and theoretical study

Author: Claude Dedonder-Lardeux, Weiwei Xie, Johannes Ehrmaier, Wolfgang Domcke, Juan-Pablo Aranguren, Xiang Huang, Andrzej L. Sobolewski, Christophe Jouvet, Jennifer A. Noble, Physique des interactions ioniques et moléculaires (PIIM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institute of Physics, Polish Academy of Sciences, Polska Akademia Nauk = Polish Academy of Sciences (PAN), Theoretische Chemie, TU Munchen, Germany, Department of Chemistry, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), and ANR-17-CE05-0005,WSPLIT,Dissociation photo induite de l'eau par chromophores organiques(2017)
Subjects: [PHYS]Physics [physics], Materials science, Electrolysis of water, Radical, General Physics and Astronomy, 02 engineering and technology, Chromophore, 010402 general chemistry, 021001 nanoscience & nanotechnology, Photochemistry, 7. Clean energy, 01 natural sciences, 0104 chemical sciences, Artificial photosynthesis, 13. Climate action, Photocatalysis, Molecule, Physics::Chemical Physics, Physical and Theoretical Chemistry, 0210 nano-technology, Spectroscopy, Molecular beam
Abstract: International audience; The photocatalytic oxidation of water with molecular or polymeric N-heterocyclic chromophores is a topic of high current interest in the context of artificial photosynthesis, that is, the conversion of solar energy to clean fuels. Hydrogen-bonded clusters of N-heterocycles with water molecules in a molecular beam are simple model systems for which the basic mechanisms of photochemical water oxidation can be studied under well-defined conditions. In this work, we explored the photoinduced H-atom transfer reaction in pyrimidine-water clusters yielding pyrimidinyl and hydroxyl radicals with laser spectroscopy, mass spectrometry and trajectory-based ab initio molecular dynamics simulations. The oxidation of water by photoexcited pyrimidine is unequivocally confirmed by the detection of the pyrimidinyl radical. The dynamics simulations provide information on the time scales and branching ratios of the reaction. While relaxation to local minima of the S1 potential-energy surface is the dominant reaction channel, the H-atom transfer reaction occurs on ultrafast time scales (faster than about 100 fs) with a branching ratio of a few percent. From the relaxed population in the S1 state, H-atom transfer yielding pyrimidinyl and hydroxyl radicals can occur on much longer time scales (picoseconds to nanoseconds) by H-atom tunneling.
Published: 2020

11. Divergent Evolution of Legionella RCC1 Repeat Effectors Defines the Range of Ran GTPase Cycle Targets

Author: Swart, A Leoni, Steiner, Bernhard, Gomez-Valero, Laura, Schütz, Sabina, Hannemann, Mandy, Janning, Petra, Irminger, Michael, Rothmeier, Eva, Buchrieser, Carmen, Itzen, Aymelt, Panse, Vikram Govind, Hilbi, Hubert, Institute of Medical Microbiology [Zurich], Universität Zürich [Zürich] = University of Zurich (UZH), Biologie des Bactéries intracellulaires - Biology of Intracellular Bacteria, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Center for Integrated Protein Science (CIPSM), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz-Zentrum München (HZM)-Ludwig Maximilian University of Munich [Germany] (LMU München), Max-Planck-Institut für Molekulare Physiologie, Max-Planck-Gesellschaft, Max Von Pettenkofer Institute (MVP), Ludwig-Maximilians-Universität München (LMU), Institute of Biochemistry and Signal Transduction [Hamburg, Germany], Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Research in the laboratory of H.H. was supported by the Swiss National Science Foundation (SNF, 31003A_153200 and 31003A_175557), the OPO Foundation, and the Novartis Foundation for Medical-Biological Research. A. Welin was supported by a grant from the Swedish Research Council (2014-396). V.G.P. was supported by grants from the Swiss National Science Foundation, NCCR RNA & Disease, Novartis Foundation for Medical-Biological Research and the Olga Mayenfisch Foundation., Work in the laboratory of C.B. was financed by the Institut Pasteur and by grant ANR-10-LABX-62-IBEID., We thank Amanda Welin for performing imaging flow cytometry experiments and Nadia Keller for flow cytometry analysis., Confocal laser scanning microscopy and imaging flow cytometry were performed using equipment of the Center of Microscopy and Image Analysis, University of Zurich. Proteomics analysis was performed at the Functional Genomics Center Zürich., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), University of Zurich, Hilbi, Hubert, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU)-Helmholtz Zentrum München = German Research Center for Environmental Health
Subjects: 10179 Institute of Medical Microbiology, 2404 Microbiology, Legionella, 610 Medicine & health, Acanthamoeba, macrophage, host-pathogen interaction, bacterial evolution, Microbiology, type IV secretion, QR1-502, phosphoinositide lipid, small GTPase, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], vesicle trafficking, 2406 Virology, 570 Life sciences, biology, guanine nucleotide exchange factor, Dictyostelium, amoeba, effector protein, microtubule, pathogen vacuole
Abstract: International audience; Legionella pneumophila governs its interactions with host cells by secreting >300 different "effector" proteins. Some of these effectors contain eukaryotic domains such as the RCC1 (regulator of chromosome condensation 1) repeats promoting the activation of the small GTPase Ran. In this report, we reveal a conserved pattern of L. pneumophila RCC1 repeat genes, which are distributed in two main clusters of strains. Accordingly, strain Philadelphia-1 contains two RCC1 genes implicated in bacterial virulence, legG1 (Legionella eukaryotic gene 1), and ppgA, while strain Paris contains only one, pieG. The RCC1 repeat effectors localize to different cellular compartments and bind distinct components of the Ran GTPase cycle, including Ran modulators and the small GTPase itself, and yet they all promote the activation of Ran. The pieG gene spans the corresponding open reading frames of legG1 and a separate adjacent upstream gene, lpg1975. legG1 and lpg1975 are fused upon addition of a single nucleotide to encode a protein that adopts the binding specificity of PieG. Thus, a point mutation in pieG splits the gene, altering the effec-tor target. These results indicate that divergent evolution of RCC1 repeat effectors defines the Ran GTPase cycle targets and that modulation of different components of the cycle might fine-tune Ran activation during Legionella infection.IMPORTANCE Legionella pneumophila is a ubiquitous environmental bacterium which, upon inhalation, causes a life-threatening pneumonia termed Legionnaires' disease. The opportunistic pathogen grows in amoebae and macrophages by employing a "type IV" secretion system, which secretes more than 300 different "effec-tor" proteins into the host cell, where they subvert pivotal processes. The function of many of these effector proteins is unknown, and their evolution has not been studied. L. pneumophila RCC1 repeat effectors target the small GTPase Ran, a molecular switch implicated in different cellular processes such as nucleocytoplasmic transport and microtubule cytoskeleton dynamics. We provide evidence that one or more RCC1 repeat genes are distributed in two main clusters of L. pneumophila strains and have divergently evolved to target different components of the Ran GTPase activation cycle at different subcellular sites. Thus, L. pneumophila employs a sophisticated strategy to subvert host cell Ran GTPase during infection.
Published: 2020

12. PROTEIN PHOSPHATASE 2A-B′ γ Controls Botrytis cinerea Resistance and Developmental Leaf Senescence

Author: Zsófia Winter, Shengchun Li, Graham Noctor, Mikael Brosché, Saijaliisa Kangasjärvi, Katariina Vuorinen, Verena Jeschke, Meike Burow, Eva-Mari Aro, Peter J. Gollan, Jarkko Salojärvi, Moona Rahikainen, Guido Durian, Kirk Overmyer, Erich Glawischnig, Jaakko Kangasjärvi, Molecular Plant Biology, University of Turku, DynaMo Center of Excellence for Dynamic Molecular Interactions (DynaMo), Department of Plant and Environmental Sciences [Copenhagen], Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Organismal and Evolutionary Biology Research Program, Faculty of Biological and Environmental Sciences, Viikki Plant Science Centre, University of Helsinki-University of Helsinki-Viikki Plant Science Centre, University of Helsinki-University of Helsinki, Chair of Genetics, Department of Plant Sciences, Technical University of Munich (TUM)-Technical University of Munich (TUM), Institut des Sciences des Plantes de Paris-Saclay (IPS2 (UMR_9213 / UMR_1403)), Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Academy of FinlandEuropean Commission289687307719303757317218Academy of Finland307335University of Turku Doctoral Programme in Molecular Life Sciences Turku University Foundation Finnish Cultural Foundation Danmarks Grundforskningsfond99Villumfonden 13169Scandinavian Society for Plant Physiology German Research Foundation (DFG)GL346/5University of Helsinki Doctoral Program in Plant Science Ella and Georg Ehrnrooth Foundation Finnish Functional Genomics Centre, University of Turku Abo Akademi Biocenter Finland, Organismal and Evolutionary Biology Research Programme, Viikki Plant Science Centre (ViPS), Plant stress and natural variation, Bioinformatics for Molecular Biology and Genomics (BMBG), Plant ROS-Signalling, Doctoral Programme in Plant Sciences, Plant-Fungal Interactions Group, University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH)-Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Viikki Plant Science Centre, Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), and Université d'Évry-Val-d'Essonne (UEVE)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 0106 biological sciences, Senescence, Physiology, Transcription Factor, Arabidopsis, Expression, Plant Science, Biology, Plant disease resistance, 01 natural sciences, Gene, chemistry.chemical_compound, Genetics, Defense, Arabidopsis thaliana, Responses, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Receptor-like Kinase, Protein kinase A, Botrytis cinerea, Disease Resistance, 2. Zero hunger, fungi, food and beverages, Protein phosphatase 2, biology.organism_classification, 11831 Plant biology, Salicylic-acid, Cell biology, chemistry, 2a, Salicylic acid, 010606 plant biology & botany
Abstract: International audience; Plants optimize their growth and survival through highly integrated regulatory networks that coordinate defensive measures and developmental transitions in response to environmental cues. Protein phosphatase 2A (PP2A) is a key signaling component that controls stress reactions and growth at different stages of plant development, and the PP2A regulatory subunit PP2A-B'gamma is required for negative regulation of pathogenesis responses and for maintenance of cell homeostasis in short-day conditions. Here, we report molecular mechanisms by which PP2A-B'gamma regulates Botrytis cinerea resistance and leaf senescence in Arabidopsis (Arabidopsis thaliana). We extend the molecular functionality of PP2A-B'gamma to a protein kinase-phosphatase interaction with the defense-associated calcium-dependent protein kinase CPK1 and present indications this interaction may function to control CPK1 activity. In presenescent leaf tissues, PP2A-B'gamma is also required to negatively control the expression of salicylic acid-related defense genes, which have recently proven vital in plant resistance to necrotrophic fungal pathogens. In addition, we find the premature leaf yellowing of pp2a-b'gamma depends on salicylic acid biosynthesis via SALICYLIC ACID INDUCTION DEFICIENT2 and bears the hallmarks of developmental leaf senescence. We propose PP2A-B'gamma age-dependently controls salicylic acid-related signaling in plant immunity and developmental leaf senescence.
Published: 2020

13. A real-time cell-binding assay reveals dynamic features of STxB-Gb3 cointernalization and STxB-mediated cargo delivery into cancer cells

Author: Grzegorz M Popowicz, Jos Buijs, Valeria Napolitano, Giulia Opassi, U. Helena Danielson, Hanna Björkelund, Grzegorz Dubin, João Crispim Encarnação, Hélène Munier-Lehmann, Karl Andersson, Ridgeview Instruments AB [Uppsala, Sueden], Department of Immunology, Genetics and Pathology [Uppsala, Sueden] (IGP), Uppsala University, Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Department of Chemistry [Uppsala, Sueden], Biomedical Center = Biomedicinskt centrum [Uppsala, Sueden] (BMC), Uppsala University-Uppsala University, Malopolska Centre of Biotechnology [Krakow] (MCB), Helmholtz-Zentrum München (HZM), Center for Integrated Protein Science (CIPSM), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz-Zentrum München (HZM)-Ludwig Maximilian University of Munich [Germany] (LMU München), Chimie et Biocatalyse, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], This project has received funding from the European Union's Framework Programme for Research and Innovation Horizon 2020 (2014–2020) under the Marie Sklodowska‐Curie Grant Agreement No. 675555, Accelerated Early staGe drug discovery (AEGIS)., Microscopic imaging was performed with equipment maintained by the BioVis Platform at Uppsala University. We thank to Dr Arie Geerlof and Dr André Mourão (Institute of Structural Biology, Helmholtz Zentrum München) for providing help on protein expression and purification of the STxB constructs., European Project: 675555,H2020,H2020-MSCA-ITN-2015,AEGIS(2016), Helmholtz Zentrum München = German Research Center for Environmental Health, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU)-Helmholtz Zentrum München = German Research Center for Environmental Health, and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: media_common.quotation_subject, [SDV]Life Sciences [q-bio], Cell, education, Biophysics, Globotriaosylceramide, cell surface receptor, Biological Transport, Active, Shiga Toxins, Biochemistry, real-time cell-binding assays, 03 medical and health sciences, chemistry.chemical_compound, [SPI]Engineering Sciences [physics], Structural Biology, Cell surface receptor, receptor internalization, Neoplasms, Genetics, medicine, binding kinetics, cancer, Humans, Internalization, Molecular Biology, Binding Kinetics, Cancer, Cell Surface Receptor, Real-time Cell-binding Assays, Receptor Internalization, Shiga Toxin, real-time cell- binding assays, 030304 developmental biology, media_common, 0303 health sciences, Drug Carriers, Chemistry, Trihexosylceramides, 030302 biochemistry & molecular biology, Biochemistry and Molecular Biology, Cell Biology, Shiga toxin, Small molecule, Receptor–ligand kinetics, 3. Good health, Cell biology, ddc, medicine.anatomical_structure, Cancer cell, Biological Assay, K562 Cells, HT29 Cells, Intracellular, Biokemi och molekylärbiologi
Abstract: International audience; The interaction between the Shiga toxin B-subunit (STxB) and its globotriaosylceramide receptor (Gb3) has a high potential for being exploited for targeted cancer therapy. The primary goal of this study was to evaluate the capacity of STxB to carry small molecules and proteins as cargo into cells. For this purpose, an assay was designed to provide real-time information about the StxB-Gb3 interaction as well as the dynamics and mechanism of the internalization process. The assay revealed the ability to distinguish the process of binding to the cell surface from internalization and presented the importance of receptor and STxB clustering for internalization. The overall setup demonstrated that the binding mechanism is complex, and the concept of affinity is difficult to apply. Hence, time-resolved methods, providing detailed information about the interaction of STxB with cells, are critical for the optimization of intracellular delivery.
Published: 2020

14. Bi-allelic HPDL Variants Cause a Neurodegenerative Disease Ranging from Neonatal Encephalopathy to Adolescent-Onset Spastic Paraplegia

Author: Andrea Bevot, Diana Chiang, Laurence Colleaux, Christian A. Hübner, Hans Hartmann, Zhao-Qi Wang, Tobias B. Haack, Ralf A. Husain, J. Christopher Hennings, Kevin Rostasy, Michael C. Kruer, Hossein Darvish, Olaf Riess, Andy Cheuk Him Ng, Marion Döbler-Neumann, Tim M. Strom, Lucia Laugwitz, Johannes A. Mayr, Thomas Klopstock, Xenia Kobeleva, René G. Feichtinger, Saghar Ghasemi Firouzabadi, Rebecca Buchert, Amelie J. Müller, Matias Wagner, Antje K. Huebner, Shrikant Mane, Marcus Deschauer, Ingeborg Krägeloh-Mann, Abdelkrim Saadi, Ulrich Brandl, Penelope E. Bonnen, Christian Marx, Isabell Cordts, Thomas Klockgether, Abbas Tafakhori, Thomas Meitinger, Florentine Radelfahr, Arnaud Besse, Mona Grimmel, Marc Sturm, Saskia B. Wortmann, Somayeh Bakhtiari, Francois V. Bolduc, Stefanie Beck-Woedl, Thomas Nägele, Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Jena University Hospital [Jena], University of Tübingen, Helmholtz-Zentrum München (HZM), Leibniz Institute on Aging - Fritz Lipmann Institute (FLI), Leibniz Association, Paracelsus Medizinische Privatuniversität = Paracelsus Medical University (PMU), Université d'Alger 1 (Benyoucef Benkhedda), Universität Witten Herdecke, German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), University Children's Hospital of Tübingen, Partenaires INRAE, Hannover Medical School [Hannover] (MHH), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Technische Universität München [München] (TUM), University of Bonn, Semnan University, University of Arizona, Baylor College of Medicine (BCM), Baylor University, University of Alberta, Tehran University of Medical Sciences (TUMS), Yale University School of Medicine, University of Social Welfare and Rehabilitation Sciences [Tehran], Universitätsklinikum Tübingen - University Hospital of Tübingen, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Munich Cluster for systems neurology [Munich] (SyNergy), Technische Universität München [München] (TUM)-Ludwig-Maximilians-Universität München (LMU), Amalia Children’s Hospital [Nijmegen, The Netherlands], Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU), Helmholtz Zentrum München = German Research Center for Environmental Health, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Yale School of Medicine [New Haven, Connecticut] (YSM), and COLLEAUX, Laurence
Subjects: 0301 basic medicine, Male, mitochondrial metabolism, Neurological disorder, Mitochondrion, 0302 clinical medicine, Spastic, Child, Genetics (clinical), Exome sequencing, ComputingMilieux_MISCELLANEOUS, Brain Diseases, genetics [Brain Diseases], Neurodegenerative Diseases, encephalopathy, Mitochondria, 3. Good health, Pedigree, developmental delay, Phenotype, Female, genetics [Mitochondrial Proteins], movement disorder, medicine.symptom, Adult, Adolescent, Hereditary spastic paraplegia, Encephalopathy, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Developmental Delay, Exome Sequencing, Hereditary Spastic Paraplegia, Hpdl, Leigh-like Syndrome, Mitochondrial Metabolism, Movement Disorder, Mitochondrial Proteins, Leigh-like syndrome, 03 medical and health sciences, Young Adult, Report, ddc:570, genetics [Spastic Paraplegia, Hereditary], Genetics, medicine, Humans, Spasticity, Amino Acid Sequence, hereditary spastic paraplegia, Allele, Alleles, Spastic Paraplegia, Hereditary, business.industry, HPDL, medicine.disease, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, genetics [Neurodegenerative Diseases], Immunology, genetics [Mitochondria], business, exome sequencing, 030217 neurology & neurosurgery
Abstract: International audience; We report bi-allelic pathogenic HPDL variants as a cause of a progressive, pediatric-onset spastic movement disorder with variable clinical presentation. The single-exon gene HPDL encodes a protein of unknown function with sequence similarity to 4-hydroxyphenylpyruvate dioxygenase. Exome sequencing studies in 13 families revealed bi-allelic HPDL variants in each of the 17 individuals affected with this clinically heterogeneous autosomal-recessive neurological disorder. HPDL levels were significantly reduced in fibroblast cell lines derived from more severely affected individuals, indicating the identified HPDL variants resulted in the loss of HPDL protein. Clinical presentation ranged from severe, neonatal-onset neurodevelopmental delay with neuroimaging findings resembling mitochondrial encephalopathy to milder manifestation of adolescent-onset, isolated hereditary spastic paraplegia. All affected individuals developed spasticity predominantly of the lower limbs over the course of the disease. We demonstrated through bioinformatic and cellular studies that HPDL has a mitochondrial localization signal and consequently localizes to mitochondria suggesting a putative role in mitochondrial metabolism. Taken together, these genetic, bioinformatic, and functional studies demonstrate HPDL is a mitochondrial protein, the loss of which causes a clinically variable form of pediatric-onset spastic movement disorder.
Published: 2020

15. A Statistical Framework for Generating Microstructures of Two-Phase Random Materials: Application to Fatigue Analysis

Author: Barbara Wohlmuth, Andrei Constantinescu, J. Tinsley Oden, Patrick Le Tallec, Ustim Khristenko, Institute for Numerical Mathematics, Department of Mathematics [Munich], Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Laboratoire de mécanique des solides (LMS), École polytechnique (X)-Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Mathematical and Mechanical Modeling with Data Interaction in Simulations for Medicine (M3DISIM), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)-Mines Paris - PSL (École nationale supérieure des mines de Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Institute for Computational Engineering and Sciences [Austin] (ICES), University of Texas at Austin [Austin], and École polytechnique (X)-MINES ParisTech - École nationale supérieure des mines de Paris
Subjects: Materials science, FOS: Physical sciences, General Physics and Astronomy, Applied Physics (physics.app-ph), 010103 numerical & computational mathematics, [SPI.MECA.MSMECA]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Materials and structures in mechanics [physics.class-ph], 01 natural sciences, Random materials, Phase (matter), FOS: Mathematics, 82D30, 60G60, 62M40, 65C60, 62F15, Mathematics - Numerical Analysis, Statistical physics, 0101 mathematics, Uncertainty quantification, Condensed Matter - Statistical Mechanics, Statistical Mechanics (cond-mat.stat-mech), Ecological Modeling, Numerical Analysis (math.NA), Physics - Applied Physics, General Chemistry, Microstructure, Computer Science Applications, 010101 applied mathematics, Random heterogeneous material, Fatigue Analysis, Modeling and Simulation, Gaussian level-set, Two-phase material, Matérn covariance
Abstract: International audience; Random microstructures of heterogeneous materials play a crucial role in the material macroscopic behavior and in predictions of its effective properties. A common approach to modeling random multiphase materials is to develop so-called surrogate models approximating statistical features of the material. However , the surrogate models used in fatigue analysis usually employ simple mi-crostructure, consisting of ideal geometries such as ellipsoidal inclusions, which generally does not capture complex geometries. In this paper, we introduce a simple but flexible surrogate microstructure model for two-phase materials through a level-cut of a Gaussian random field with covariance of Matérn class. Such parametrization of the covariance function allows for the representation of a few key design parameters while representing the geometry of inclusions in a more general setting for a large class of random heterogeneous two-phase media. In addition to the traditional morphology descriptors such as porosity, size and aspect ratio, it provides control of the regularity of the inclusions interface and sphericity. These parameters are estimated from a small number of real material images using Bayesian inversion. An efficient process of evaluating the samples, based on the Fast Fourier Transform, makes possible the use of Monte-Carlo methods to estimate statistical properties for the quantities of interest in a given material class. We demonstrate the overall framework of the use of the surrogate material model in application to the uncertainty quantification in fatigue analysis, its feasibility and efficiency, and its role in the microstructure design.
Published: 2020

16. Genetic variants in components of the NALCN–UNC80–UNC79 ion channel complex cause a broad clinical phenotype (NALCN channelopathies)

Author: Peter Bauer, Nuria C. Bramswig, Hartmut Engels, Abdelrahim Abdrabou Sadek, Hasnaa M. Elbendary, Beate Albrecht, Lara Segebrecht, Joseph G. Gleeson, Boris Keren, Diane Doummar, Arndt Rolfs, Jennifer McEvoy-Venneri, Nicole Philip, Christel Depienne, Thomas Wieland, Samira Ismail, Laurent Villard, Tim M. Strom, Michèle Mayer, Aida M. Bertoli-Avella, Maha S. Zaki, Svetlana Gorokhova, Alma Kuechler, Dagmar Wieczorek, Caroline Nava, Nathalie Dorison, André Mégarbané, Amal Alhashem, Stéphanie Valence, Cyril Mignot, Delphine Héron, Valentina Stanley, Isabelle Marey, Nadja Ehmke, Nouriya Al-Sannaa, Hermann-Josef Lüdecke, Sarar Mohamed, Denise Horn, Camille Trautman, Kiely N. James, Katharina Bröhl, Cecile Ravix, Aida I. Al Aqeel, Maissa Bah, Mahmoud Y. Issa, Institut für Humangenetik [Essen], Universitätsklinikum Essen, Neurologie et thérapeutique expérimentale, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM), Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de neuropédiatrie [Trousseau], Centre de Génétique Moléculaire et Chromosomique du GH Pitié-Salpêtrière, Charité - Universitätsmedizin Berlin / Charite - University Medicine Berlin, Service de génétique [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Service de biochimie et de génétique moléculaire [CHU Cochin], CHU Cochin [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Pitié-Salpêtrière [APHP], Unité Fonctionnelle de Génétique Médicale, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP]-Centre de Référence des Déficiences Intellectuelles de Causes Rares, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), 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)-CHU Pitié-Salpêtrière [APHP], Département de génétique médicale [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Albrecht-Kossel-Institut fur Neuroregeneration, Universität Rostock, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Trousseau [APHP], Institute of Human Genetics, Helmholtz-Zentrum München (HZM)-Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Rheinische Friedrich-Wilhelms-Universität Bonn, Technische Universität München [München] (TUM)-Helmholtz-Zentrum München (HZM)-German Research Center for Environmental Health, Laboratory of Neurogenetics, Howard Hughes Medical Institute, Department of Neurosciences, University of California [San Diego] (UC San Diego), University of California-University of California, Universität Duisburg-Essen [Essen], Institute of Human Genetics - Institut für Humangenetik [Essen], Universitätsklinikum Essen [Universität Duisburg-Essen] (Uniklinik Essen)-Universitat Duisberg-Essen, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR70-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Pitié-Salpêtrière [AP-HP], Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], 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)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-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)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz-Zentrum München (HZM)-German Research Center for Environmental Health, Helmholtz Zentrum München = German Research Center for Environmental Health-Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz Zentrum München = German Research Center for Environmental Health, University of California (UC)-University of California (UC), and Universität Duisburg-Essen = University of Duisburg-Essen [Essen]
Subjects: Adult, Genetic Markers, Male, 0301 basic medicine, Adolescent, Developmental Disabilities, [SDV]Life Sciences [q-bio], Medizin, Disease, Biology, Ion Channels, Sodium Channels, Article, Young Adult, 03 medical and health sciences, Ion channel complex, Genetic variation, Genetics, medicine, Humans, Missense mutation, Child, ComputingMilieux_MISCELLANEOUS, Genetics (clinical), [SDV.GEN]Life Sciences [q-bio]/Genetics, Psychomotor retardation, Infant, Newborn, Genetic Variation, Infant, Membrane Proteins, Phenotype, Hypotonia, Human genetics, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Child, Preschool, Channelopathies, Female, medicine.symptom, Carrier Proteins
Abstract: NALCN is a conserved cation channel, which conducts a permanent sodium leak current and regulates resting membrane potential and neuronal excitability. It is part of a large ion channel complex, the "NALCN channelosome", consisting of multiple proteins including UNC80 and UNC79. The predominant neuronal expression pattern and its function suggest an important role in neuronal function and disease. So far, biallelic NALCN and UNC80 variants have been described in a small number of individuals leading to infantile hypotonia, psychomotor retardation, and characteristic facies 1 (IHPRF1, OMIM 615419) and 2 (IHPRF2, OMIM 616801), respectively. Heterozygous de novo NALCN missense variants in the S5/S6 pore-forming segments lead to congenital contractures of the limbs and face, hypotonia, and developmental delay (CLIFAHDD, OMIM 616266) with some clinical overlap. In this study, we present detailed clinical information of 16 novel individuals with biallelic NALCN variants, 1 individual with a heterozygous de novo NALCN missense variant and an interesting clinical phenotype without contractures, and 12 individuals with biallelic UNC80 variants. We report for the first time a missense NALCN variant located in the predicted S6 pore-forming unit inherited in an autosomal-recessive manner leading to mild IHPRF1. We show evidence of clinical variability, especially among IHPRF1-affected individuals, and discuss differences between the IHPRF1- and IHPRF2 phenotypes. In summary, we provide a comprehensive overview of IHPRF1 and IHPRF2 phenotypes based on the largest cohort of individuals reported so far and provide additional insights into the clinical phenotypes of these neurodevelopmental diseases to help improve counseling of affected families.
Published: 2018

17. N-Heterocyclic carbenes on close-packed coinage metal surfaces: bis-carbene metal adatom bonding scheme of monolayer films on Au, Ag and Cu

Author: Francesco Allegretti, Bodong Zhang, Johannes V. Barth, Felix Haag, Anthoula C. Papageorgiou, Guillaume Médard, Ari P. Seitsonen, Joachim Reichert, Li Jiang, Bernhard Kuster, Chair of Molecular Nanoscience and Chemical Physics of Interfaces (E20), Department of Physics, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Chair of Proteomics and Bioanalytics, Technical University Munich, 85354 Freising-Weihenstephan, and Département de Chimie, École Normale Supérieure
Subjects: [PHYS]Physics [physics], Inorganic chemistry, Charge density, 02 engineering and technology, General Chemistry, 010402 general chemistry, 021001 nanoscience & nanotechnology, 01 natural sciences, ddc, 0104 chemical sciences, Metal, Crystallography, chemistry.chemical_compound, chemistry, X-ray photoelectron spectroscopy, visual_art, Monolayer, visual_art.visual_art_medium, Molecule, Density functional theory, 0210 nano-technology, Carbene, Quantum tunnelling
Abstract: International audience; By means of scanning tunnelling microscopy (STM), complementary density functional theory (DFT) and X-ray photoelectron spectroscopy (XPS) we investigate the binding and self-assembly of a saturated molecular layer of model N-heterocyclic carbene (NHC) on Cu(111), Ag(111) and Au(111) surfaces under ultra-high vacuum (UHV) conditions. XPS reveals that at room temperature, coverages up to a monolayer exist, with the molecules engaged in metal carbene bonds. On all three surfaces, we resolve similar arrangements, which can be interpreted only in terms of mononuclear M(NHC)2 (M = Cu, Ag, Au) complexes, reminiscent of the paired bonding of thiols to surface gold adatoms. Theoretical investigations for the case of Au unravel the charge distribution of a Au(111) surface covered by Au(NHC)2 and reveal that this is the energetically preferential adsorption configuration.
Published: 2017

18. Heterozygous Variants in KMT2E Cause a Spectrum of Neurodevelopmental Disorders and Epilepsy

Author: Anne H. O’Donnell-Luria, Lynn S. Pais, Víctor Faundes, Jordan C. Wood, Abigail Sveden, Victor Luria, Rami Abou Jamra, Andrea Accogli, Kimberly Amburgey, Britt Marie Anderlid, Silvia Azzarello-Burri, Alice A. Basinger, Claudia Bianchini, Lynne M. Bird, Rebecca Buchert, Wilfrid Carre, Sophia Ceulemans, Perrine Charles, Helen Cox, Lisa Culliton, Aurora Currò, Florence Demurger, James J. Dowling, Benedicte Duban-Bedu, Christèle Dubourg, Saga Elise Eiset, Luis F. Escobar, Alessandra Ferrarini, Tobias B. Haack, Mona Hashim, Solveig Heide, Katherine L. Helbig, Ingo Helbig, Raul Heredia, Delphine Héron, Bertrand Isidor, Amy R. Jonasson, Pascal Joset, Boris Keren, Fernando Kok, Hester Y. Kroes, Alinoë Lavillaureix, Xin Lu, Saskia M. Maas, Gustavo H.B. Maegawa, Carlo L.M. Marcelis, Paul R. Mark, Marcelo R. Masruha, Heather M. McLaughlin, Kirsty McWalter, Esther U. Melchinger, Saadet Mercimek-Andrews, Caroline Nava, Manuela Pendziwiat, Richard Person, Gian Paolo Ramelli, Luiza L.P. Ramos, Anita Rauch, Caitlin Reavey, Alessandra Renieri, Angelika Rieß, Amarilis Sanchez-Valle, Shifteh Sattar, Carol Saunders, Niklas Schwarz, Thomas Smol, Myriam Srour, Katharina Steindl, Steffen Syrbe, Jenny C. Taylor, Aida Telegrafi, Isabelle Thiffault, Doris A. Trauner, Helio van der Linden, Silvana van Koningsbruggen, Laurent Villard, Ida Vogel, Julie Vogt, Yvonne G. Weber, Ingrid M. Wentzensen, Elysa Widjaja, Jaroslav Zak, Samantha Baxter, Siddharth Banka, Lance H. Rodan, Jeremy F. McRae, Stephen Clayton, Tomas W. Fitzgerald, Joanna Kaplanis, Elena Prigmore, Diana Rajan, Alejandro Sifrim, Stuart Aitken, Nadia Akawi, Mohsan Alvi, Kirsty Ambridge, Daniel M. Barrett, Tanya Bayzetinova, Philip Jones, Wendy D. Jones, Daniel King, Netravathi Krishnappa, Laura E. Mason, Tarjinder Singh, Adrian R. Tivey, Munaza Ahmed, Uruj Anjum, Hayley Archer, Ruth Armstrong, Jana Awada, Meena Balasubramanian, Diana Baralle, Angela Barnicoat, Paul Batstone, David Baty, Chris Bennett, Jonathan Berg, Birgitta Bernhard, A. Paul Bevan, Maria Bitner-Glindzicz, Edward Blair, Moira Blyth, David Bohanna, Louise Bourdon, David Bourn, Lisa Bradley, Angela Brady, Simon Brent, Carole Brewer, Kate Brunstrom, David J. Bunyan, John Burn, Natalie Canham, Bruce Castle, Kate Chandler, Elena Chatzimichali, Deirdre Cilliers, Angus Clarke, Susan Clasper, Jill Clayton-Smith, Virginia Clowes, Andrea Coates, Trevor Cole, Irina Colgiu, Amanda Collins, Morag N. Collinson, Fiona Connell, Nicola Cooper, Lara Cresswell, Gareth Cross, Yanick Crow, Mariella D’Alessandro, Tabib Dabir, Rosemarie Davidson, Sally Davies, Dylan de Vries, John Dean, Charu Deshpande, Gemma Devlin, Abhijit Dixit, Angus Dobbie, Alan Donaldson, Dian Donnai, Deirdre Donnelly, Carina Donnelly, Angela Douglas, Sofia Douzgou, Alexis Duncan, Jacqueline Eason, Sian Ellard, Ian Ellis, Frances Elmslie, Karenza Evans, Sarah Everest, Tina Fendick, Richard Fisher, Frances Flinter, Nicola Foulds, Andrew Fry, Alan Fryer, Carol Gardiner, Lorraine Gaunt, Neeti Ghali, Richard Gibbons, Harinder Gill, Judith Goodship, David Goudie, Emma Gray, Andrew Green, Philip Greene, Lynn Greenhalgh, Susan Gribble, Rachel Harrison, Lucy Harrison, Victoria Harrison, Rose Hawkins, Liu He, Stephen Hellens, Alex Henderson, Sarah Hewitt, Lucy Hildyard, Emma Hobson, Simon Holden, Muriel Holder, Susan Holder, Georgina Hollingsworth, Tessa Homfray, Mervyn Humphreys, Jane Hurst, Ben Hutton, Stuart Ingram, Melita Irving, Lily Islam, Andrew Jackson, Joanna Jarvis, Lucy Jenkins, Diana Johnson, Elizabeth Jones, Dragana Josifova, Shelagh Joss, Beckie Kaemba, Sandra Kazembe, Rosemary Kelsell, Bronwyn Kerr, Helen Kingston, Usha Kini, Esther Kinning, Gail Kirby, Claire Kirk, Emma Kivuva, Alison Kraus, Dhavendra Kumar, V. K. Ajith Kumar, Katherine Lachlan, Wayne Lam, Anne Lampe, Caroline Langman, Melissa Lees, Derek Lim, Cheryl Longman, Gordon Lowther, Sally A. Lynch, Alex Magee, Eddy Maher, Alison Male, Sahar Mansour, Karen Marks, Katherine Martin, Una Maye, Emma McCann, Vivienne McConnell, Meriel McEntagart, Ruth McGowan, Kirsten McKay, Shane McKee, Dominic J. McMullan, Susan McNerlan, Catherine McWilliam, Sarju Mehta, Kay Metcalfe, Anna Middleton, Zosia Miedzybrodzka, Emma Miles, Shehla Mohammed, Tara Montgomery, David Moore, Sian Morgan, Jenny Morton, Hood Mugalaasi, Victoria Murday, Helen Murphy, Swati Naik, Andrea Nemeth, Louise Nevitt, Ruth Newbury-Ecob, Andrew Norman, Rosie O’Shea, Caroline Ogilvie, Kai-Ren Ong, Soo-Mi Park, Michael J. Parker, Chirag Patel, Joan Paterson, Stewart Payne, Daniel Perrett, Julie Phipps, Daniela T. Pilz, Martin Pollard, Caroline Pottinger, Joanna Poulton, Norman Pratt, Katrina Prescott, Sue Price, Abigail Pridham, Annie Procter, Hellen Purnell, Oliver Quarrell, Nicola Ragge, Raheleh Rahbari, Josh Randall, Julia Rankin, Lucy Raymond, Debbie Rice, Leema Robert, Eileen Roberts, Jonathan Roberts, Paul Roberts, Gillian Roberts, Alison Ross, Elisabeth Rosser, Anand Saggar, Shalaka Samant, Julian Sampson, Richard Sandford, Ajoy Sarkar, Susann Schweiger, Richard Scott, Ingrid Scurr, Ann Selby, Anneke Seller, Cheryl Sequeira, Nora Shannon, Saba Sharif, Charles Shaw-Smith, Emma Shearing, Debbie Shears, Eamonn Sheridan, Ingrid Simonic, Roldan Singzon, Zara Skitt, Audrey Smith, Kath Smith, Sarah Smithson, Linda Sneddon, Miranda Splitt, Miranda Squires, Fiona Stewart, Helen Stewart, Volker Straub, Mohnish Suri, Vivienne Sutton, Ganesh Jawahar Swaminathan, Elizabeth Sweeney, Kate Tatton-Brown, Cat Taylor, Rohan Taylor, Mark Tein, I. Karen Temple, Jenny Thomson, Marc Tischkowitz, Susan Tomkins, Audrey Torokwa, Becky Treacy, Claire Turner, Peter Turnpenny, Carolyn Tysoe, Anthony Vandersteen, Vinod Varghese, Pradeep Vasudevan, Parthiban Vijayarangakannan, Emma Wakeling, Sarah Wallwark, Jonathon Waters, Astrid Weber, Diana Wellesley, Margo Whiteford, Sara Widaa, Sarah Wilcox, Emily Wilkinson, Denise Williams, Nicola Williams, Louise Wilson, Geoff Woods, Christopher Wragg, Michael Wright, Laura Yates, Michael Yau, Chris Nellåker, Michael Parker, Helen V. Firth, Caroline F. Wright, David R. FitzPatrick, Jeffrey C. Barrett, Matthew E. Hurles, Department of Medicine 1, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Center for Medical Genetics, Istituto di Scienze e Tecnologie della Cognizione, Consiglio Nazionale delle Ricerche (ISTC, CNR), Istituto di Scienze e Tecnologie della Cognizione, Station biologique de Roscoff [Roscoff] (SBR), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Génétique médicale [Centre Hospitalier de Vannes], Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA), Department of Pediatrics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Centre de Génétique Chromosomique [Hôpital Saint Vincent de Paul], Hôpital Saint Vincent de Paul-Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Service de génétique médicale, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Institute of Human Genetics, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz Zentrum München = German Research Center for Environmental Health, Groupe de Recherche Clinique : Déficience Intellectuelle et Autisme (GRC), Université Pierre et Marie Curie - Paris 6 (UPMC), Children’s Hospital of Philadelphia (CHOP ), Service de Génétique Médicale, Centre hospitalier universitaire de Nantes (CHU Nantes), Department of Public Health Sciences, Karolinska Institutet [Stockholm], Department of Molecular and Human Genetics, Baylor College of Medicine (BCM), Baylor University-Baylor University, Institute of Medical Genetics, Universität Zürich [Zürich] = University of Zurich (UZH), Università degli Studi di Camerino = University of Camerino (UNICAM), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), University of Oxford, GeneDx [Gaithersburg, MD, USA], Department of Clinical Genetics (Academic Medical Center, University of Amsterdam), VU University Medical Center [Amsterdam], Marseille medical genetics - Centre de génétique médicale de Marseille (MMG), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Clinical Genetics, Aarhus University Hospital, Boston Children's Hospital, Wellcome Trust Genome Campus, The Wellcome Trust Sanger Institute [Cambridge], Institute of Biomedical Engineering [Oxford] (IBME), Climatic Research Unit, University of East Anglia [Norwich] (UEA), Imperial College London, St Mary's Hospital, East Anglian Medical Genetics Service, Cytogenetics Laboratory, Addenbrooke's Hospital, Sheffield Children's NHS Foundation Trust, Regional Genetic Service, St Mary's Hospital, Manchester, Genetics, University of Southampton, Great Ormond Street Hospital for Children [London] (GOSH), Yorkshire Regional Clinical Genetics Service, Chapel Allerton Hospital, Molecular and Clinical Medicine [Dundee, UK] (School of Medicine), University of Dundee [UK]-Ninewells Hospital & Medical School [Dundee, UK], Department of Clinical Genetics, Oxford Regional Genetics Service, The Churchill hospital, North West Thames Regional Genetics, Northwick Park Hospital, Royal Devon & Exeter Hospital, Wessex Clinical Genetics Service, Wessex clinical genetics service, Manchester University NHS Foundation Trust (MFT), West Midlands Regional Genetics Service, Birmingham Women's and Children's NHS Foundation Trust, Our Lady's hospital for Sick Children, Our Lady's Hospital for Sick Children, Guy's Hospital [London], University Hospitals Leicester, University of Edinburgh, Belfast City Hospital, Ferguson-Smith Centre for Clinical Genetics, Yorkhill Hospitals, Institute of Medical Genetics, Heath Park, Cardiff, The London Clinic, Nottingham City Hospital, Clinical Genetics Department, St Michael's Hospital, Department of Genetic Medicine, Nottingham Clinical Genetics Service, Nottingham University Hospitals NHS Trust (NUH), Royal Devon and Exeter Foundation Trust, Histopathology, St. George's Hospital, Teesside Genetics Unit, James Cook University (JCU), Kansas State University, Liverpool Women's NHS Foundation Trust, Department of Medical Genetics, HMNC Brain Health, North West Thames Regional Genetics Service, Northwick Park Hospital, Harrow, Leicester Royal Infirmary, University Hospitals Leicester-University Hospitals Leicester, Ninewells Hospital and Medical School [Dundee], Academic Centre on Rare Diseases (ACoRD), University College Dublin [Dublin] (UCD), Oxford Brookes University, Institute of medicinal plant development, Chinese Academy of Medical Sciences, Newcastle Upon Tyne Hospitals NHS Trust, Service d'explorations fonctionnelles respiratoires [Lille], Department of Computer Science - Trinity College Dublin, University of Dublin, Department of Clinical Genetics (Sheffield Children’s NHS Foundation Trust), Division of Medical & Molecular Genetics, NHS Greater Glasgow & Clyde [Glasgow] (NHSGGC), Department of Clinical Genetics [Churchill Hospital], Churchill Hospital Oxford Centre for Haematology, Weizmann Institute of Science [Rehovot, Israël], Southampton General Hospital, Western General Hospital, Head of the Department of Medical Genetics, University of Birmingham [Birmingham], SW Thames Regional Genetics Service, St Georgeâ™s University of London, London, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), All Wales Medical Genetics Services, Singleton Hospital, Central Manchester University Hospitals NHS Foundation Trust, University of North Texas (UNT), Clinical Genetics, Northern Genetics Service, Newcastle University [Newcastle], United Kingdom Met Office [Exeter], Institute of Medical Genetics (University Hospital of Wales), University Hospital of Wales (UHW), West Midlands Regional Genetics Laboratory and Clinical Genetics Unit, Birmingham Women's Hospital, Laboratory of Molecular Genetics, National Institute of Child Health and Human Development, National Institutes of Health, Department of Genetics, Cell- and Immunobiology, Semmelweis University, University Hospitals Bristol, Marketing (MKT), EESC-GEM Grenoble Ecole de Management, Addenbrookes Hospital, West of Scotland Genetics Service (Queen Elizabeth University Hospital), University Hospital Birmingham Queen Elizabeth, Department of Clnical Genetics, Chapel Allerton Hospital, Department of Clinical Genetics, Northampton General Hospital, Northampton, Royal Devon and Exeter Hospital [Exeter, UK] (RDEH), Guy's and St Thomas' Hospital [London], School of Computer Science, Bangor University, University Hospital Southampton, Clinical Genetics Unit, St Georges, University of London, Medical Genetics, Cardiff University, Research and Development, Futurelab, Nottingham Regional Genetics Service [Nottingham, UK], Nottingham University Hospitals NHS Trust (NUH)-City Hospital Campus [Nottingham, UK], University of St Andrews [Scotland], Clinical Genetics Service, Nottingham University Hospitals NHS Trust - City Hospital Campus, West Midlands Regional Genetics Unit, Department of Neurology, Johns Hopkins University (JHU), Oxford University Hospitals NHS Trust, St James's University Hospital, Leeds Teaching Hospitals NHS Trust, Addenbrooke's Hospital, Cambridge University NHS Trust, Institute of Human Genetics, Newcastle, Division of Biological Stress Response [Amsterdam, The Netherlands], The Netherlands Cancer Institute [Amsterdam, The Netherlands], Johns Hopkins Bloomberg School of Public Health [Baltimore], Birmingham Women’s Hospital, Department of Genetics, Portuguese Oncology Institute, Molecular Genetics, IWK Health Centre, IWK health centre, North West london hospitals NHS Trust, Department of Clinical Genetics (Queen Elizabeth University Hospital, Glasgow), Queen Elizabeth University Hospital (Glasgow), Birmingham women's hospital, Birmingham, Ethox Centre, Department of Public Health and Primary Health Care, University of Oxford, Badenoch Building, Old Road Campus, Headington, R01 HD091846, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Human Genome Research Institute, National Institutes of Health’s National Institute of Child Health and Human Development, Boston Children’s Hospital Faculty Development Fellowship, UM1HG008900, Broad Center for Mendelian Genomics, Chile’s National Commission for Scientific and Technological Research, DFG WE4896/3-1, German Research Society, WT 100127, Health Innovation Challenge Fund, Comprehensive Clinical Research Network, Skaggs-Oxford Scholarship, 10/H0305/83, Cambridge South REC, REC GEN/284/12, Republic of Ireland, WT098051, Wellcome Sanger Institute, 72160007, Comisión Nacional de Investigación Científica y Tecnológica, Children's Hospital of Philadelphia, Technische Universität Kaiserslautern, 1DH1813319, Dietmar Hopp Stiftung, National Institute for Health Research, Department of Health & Social Care, Service de neurologie 1 [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), Hôpital Saint Vincent de Paul-GHICL, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz-Zentrum München (HZM)-German Research Center for Environmental Health, Service de Génétique Cytogénétique et Embryologie [CHU Pitié-Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Università degli Studi di Camerino (UNICAM), University of Oxford [Oxford], Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU), Nottingham University Hospitals NHS Trust, Nottingham University Hospitals, SW Thames Regional Genetics Service, St Georgeâ™s University of London, London, University Hospital of Wales, Grenoble Ecole de Management, Royal Devon and Exeter Hospital, City Hospital Campus [Nottingham, UK]-Nottingham University Hospitals NHS Trust [UK], ANS - Complex Trait Genetics, Human Genetics, ARD - Amsterdam Reproduction and Development, ACS - Pulmonary hypertension & thrombosis, Service de Neurologie [CHU Pitié-Salpêtrière], IFR70-CHU Pitié-Salpêtrière [AP-HP], GHICL-Hôpital Saint Vincent de Paul, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Friedrich-Alexander d'Erlangen-Nuremberg, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Centre Hospitalier Bretagne Atlantique [Vannes], Technische Universität München [München] (TUM)-Helmholtz-Zentrum München (HZM)-German Research Center for Environmental Health, Service de Génétique et Cytogénétique [CHU Pitié-Salpêtrière], University of Zürich [Zürich] (UZH), Università di Camerino (UNICAM), Birmingham Women's Hospital Healthcare NHS Trust, University Hospitals of Leicester, Sheffield Children’s Hospital, Weizmann Institute of Science, and Grenoble Ecole de Management (GEM)
Subjects: 0301 basic medicine, Male, Microcephaly, [SDV]Life Sciences [q-bio], Haploinsufficiency, autism, epilepsy, epileptic encephalopathy, global developmental delay, H3K4 methylation, intellectual disability, KMT2E, neurodevelopmental disorder, Adolescent, Adult, Child, Child, Preschool, DNA-Binding Proteins, Epilepsy, Female, Humans, Infant, Neurodevelopmental Disorders, Pedigree, Phenotype, Young Adult, Genetic Variation, Heterozygote, 0302 clinical medicine, Neurodevelopmental disorder, Intellectual disability, Global developmental delay, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, Genetics, 0303 health sciences, Hypotonia, 030220 oncology & carcinogenesis, medicine.symptom, Rare cancers Radboud Institute for Health Sciences [Radboudumc 9], 03 medical and health sciences, Report, medicine, Journal Article, Expressivity (genetics), Preschool, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, business.industry, Macrocephaly, medicine.disease, 030104 developmental biology, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Autism, business, 030217 neurology & neurosurgery
Abstract: Contains fulltext : 206572.pdf (Publisher’s version ) (Open Access) We delineate a KMT2E-related neurodevelopmental disorder on the basis of 38 individuals in 36 families. This study includes 31 distinct heterozygous variants in KMT2E (28 ascertained from Matchmaker Exchange and three previously reported), and four individuals with chromosome 7q22.2-22.23 microdeletions encompassing KMT2E (one previously reported). Almost all variants occurred de novo, and most were truncating. Most affected individuals with protein-truncating variants presented with mild intellectual disability. One-quarter of individuals met criteria for autism. Additional common features include macrocephaly, hypotonia, functional gastrointestinal abnormalities, and a subtle facial gestalt. Epilepsy was present in about one-fifth of individuals with truncating variants and was responsive to treatment with anti-epileptic medications in almost all. More than 70% of the individuals were male, and expressivity was variable by sex; epilepsy was more common in females and autism more common in males. The four individuals with microdeletions encompassing KMT2E generally presented similarly to those with truncating variants, but the degree of developmental delay was greater. The group of four individuals with missense variants in KMT2E presented with the most severe developmental delays. Epilepsy was present in all individuals with missense variants, often manifesting as treatment-resistant infantile epileptic encephalopathy. Microcephaly was also common in this group. Haploinsufficiency versus gain-of-function or dominant-negative effects specific to these missense variants in KMT2E might explain this divergence in phenotype, but requires independent validation. Disruptive variants in KMT2E are an under-recognized cause of neurodevelopmental abnormalities.
Published: 2019

19. Conformational plasticity of the VEEV macro domain is important for binding of ADP-ribose

Author: Dioni Ntonti, Maria Birkou, Bruno Canard, Bruno Coutard, Minos-Timotheos Matsoukas, Garyfallia I. Makrynitsa, Konstantinos D. Marousis, Nicolas Papageorgiou, Georgios A. Spyroulias, Sam Asami, Detlef Bentrop, Department of Pharmacy [Patras], University of Patras, Center for Integrated Protein Science (CIPSM), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU)-Helmholtz Zentrum München = German Research Center for Environmental Health, Institute of Physiology II [Freiburg, Germany] (Faculty of Medicine), University of Freiburg [Freiburg], Architecture et fonction des macromolécules biologiques (AFMB), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), CCSD, Accord Elsevier, University of Patras [Patras], Munich Center for Integrated Protein Science [Garching, Germany] (Department Chemie), Technische Universität München [München] (TUM), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig Maximilian University of Munich [Germany] (LMU München)-Helmholtz-Zentrum München (HZM), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA), and Technical University of Munich (TUM)-Helmholtz-Zentrum München (HZM)-Ludwig Maximilian University of Munich [Germany] (LMU München)
Subjects: Magnetic Resonance Spectroscopy, Viral protein, [SDV.BBM.BS] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Molecular Conformation, Sequence (biology), Alphavirus, Molecular Dynamics Simulation, Viral Nonstructural Proteins, Virus Replication, medicine.disease_cause, Genome, Article, Encephalitis Virus, Venezuelan Equine, Conformational dynamics, 03 medical and health sciences, chemistry.chemical_compound, Macro domain, NMR spectroscopy, Protein Domains, Structural Biology, Ribose, medicine, Animals, Humans, Horses, ComputingMethodologies_COMPUTERGRAPHICS, 030304 developmental biology, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Adenosine Diphosphate Ribose, 0303 health sciences, biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], 030302 biochemistry & molecular biology, Normal mode analysis, biology.organism_classification, Viral macro domain, 3. Good health, Cell biology, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], chemistry, Viral replication, Venezuelan equine encephalitis virus, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 15N relaxation, ADP-ribose, Protein Binding
Abstract: Graphical abstract, Highlights • ADPr’s binding triggers conformational changes to the whole VEEV macro domain. • High flexibility of the loops β5-α3 and α3-β6 assist the ADPr’s binding. • Loops around ADPr site undergo a transition pathway between apo and complex state., Venezuelan equine encephalitis virus (VEEV) is a new world alphavirus which can be involved in several central nervous system disorders such as encephalitis and meningitis. The VEEV genome codes for 4 non-structural proteins (nsP), of which nsP3 contains a Macro domain. Macro domains (MD) can be found as stand-alone proteins or embedded within larger proteins in viruses, bacteria and eukaryotes. Their most common feature is the binding of ADP-ribose (ADPr), while several macro domains act as ribosylation writers, erasers or readers. Alphavirus MD erase ribosylation but their precise contribution in viral replication is still under investigation. NMR-driven titration experiments of ADPr in solution with the VEEV macro domain (in apo- and complex state) show that it adopts a suitable conformation for ADPr binding. Specific experiments indicate that the flexibility of the loops β5-α3 and α3-β6 is critical for formation of the complex and assists a wrapping mechanism for ADPr binding. Furthermore, along with this sequence of events, the VEEV MD undergoes a conformational exchange process between the apo state and a low-populated “dark” conformational state.
Published: 2019

20. Immunogenic particles with a broad antigenic spectrum stimulate cytolytic T cells and offer increased protection against EBV infection ex vivo and in mice

Author: Ming Han Tsai, Dwain G. van Zyl, Viktor Schneidt, Henri Jacques Delecluse, Anatoliy Shumilov, Herbert Fluhr, Josef Mautner, B. Schlehe, Remy Poirey, Unit F100 [Heidelberg, Allemagne], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Faculty of Biosciences [Heidelberg, Allemagne], Heidelberg University, Microbiology and infectious diseases, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ)-Institut National de la Santé et de la Recherche Médicale (INSERM), German Center for Infection Research - partner site Hannover-Braunschweig (DZIF), Frauenklinik [Heidelberg, Allemagne], Heidelberg University Hospital [Heidelberg], Children's Hospital [Munich, Allemagne], Helmholtz-Zentrum München (HZM)-Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Funding has been received from the German Cancer Research Center (Project number F100), Inserm (Project number U1074) and Deutsche Krebshilfe (70110621)., Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz Zentrum München = German Research Center for Environmental Health, and Bodescot, Myriam
Subjects: 0301 basic medicine, Epstein-Barr Virus Infections, Herpesvirus 4, Human, B Cells, Physiology, medicine.disease_cause, Biochemistry, Mice, White Blood Cells, 0302 clinical medicine, Spectrum Analysis Techniques, Animal Cells, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Immune Physiology, hemic and lymphatic diseases, Virus latency, Medicine and Health Sciences, Cytotoxic T cell, Public and Occupational Health, Biology (General), Antigens, Viral, Pathology and laboratory medicine, Immune System Proteins, T Cells, Medical microbiology, Flow Cytometry, Vaccination and Immunization, 3. Good health, Virus Latency, Lytic cycle, Spectrophotometry, Viruses, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.IMM]Life Sciences [q-bio]/Immunology, Cytophotometry, Cellular Types, Pathogens, Research Article, Herpesviruses, [SDV.IMM] Life Sciences [q-bio]/Immunology, QH301-705.5, Immune Cells, Immunology, Cytotoxic T cells, Herpesvirus Vaccines, Biology, Research and Analysis Methods, Microbiology, Virus, Antibodies, 03 medical and health sciences, Immune system, Antigen, Virology, Genetics, medicine, Animals, Epstein-Barr virus, Antigens, Antibody-Producing Cells, Molecular Biology, Blood Cells, Organisms, Viral pathogens, Biology and Life Sciences, Proteins, Cell Biology, RC581-607, medicine.disease, Epstein–Barr virus, Microbial pathogens, 030104 developmental biology, Humanized mouse, Parasitology, Preventive Medicine, Immunologic diseases. Allergy, DNA viruses, 030215 immunology, T-Lymphocytes, Cytotoxic
Abstract: The ubiquitous Epstein-Barr virus (EBV) is the primary cause of infectious mononucleosis and is etiologically linked to the development of several malignancies and autoimmune diseases. EBV has a multifaceted life cycle that comprises virus lytic replication and latency programs. Considering EBV infection holistically, we rationalized that prophylactic EBV vaccines should ideally prime the immune system against lytic and latent proteins. To this end, we generated highly immunogenic particles that contain antigens from both these cycles. In addition to stimulating EBV-specific T cells that recognize lytic or latent proteins, we show that the immunogenic particles enable the ex vivo expansion of cytolytic EBV-specific T cells that efficiently control EBV-infected B cells, preventing their outgrowth. Lastly, we show that immunogenic particles containing the latent protein EBNA1 afford significant protection against wild-type EBV in a humanized mouse model. Vaccines that include antigens which predominate throughout the EBV life cycle are likely to enhance their ability to protect against EBV infection., Author summary Human herpesviruses are tremendously successful pathogens that establish lifelong infection in a substantial proportion of the population. The oncogenic γ-herpesvirus EBV, like other herpesviruses, expresses a plethora of open-reading frames throughout its multifaceted life cycle. We have developed a prophylactic vaccine candidate in the form of immunogenic particles that contain several EBV antigens. This is in stark contrast to the vast majority of EBV vaccines candidates that contain only one or two EBV antigens. Our immunogenic particles were shown capable of stimulating several EBV-specific T-cell clones in vitro. The immunogenic particles were also capable of expanding cytolytic EBV-specific T cells ex vivo and provided a protective benefit in vivo when used as a prophylactic vaccine.
Published: 2018

21. A Machine Learning Based Approach to Application Landscape Documentation

Author: Ömer Uludağ, Florian Matthes, Saasha Nair, Ahmed Elnaggar, Gloria Bondel, Jörg Landthaler, Software Engineering for Business Information Systems [Munich], Department of Informatics [Munich], Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Robert Andrei Buchmann, Dimitris Karagiannis, Marite Kirikova, TC 8, and WG 8.1
Subjects: business.industry, Computer science, [SHS.INFO]Humanities and Social Sciences/Library and information sciences, Enterprise architecture, 020207 software engineering, 02 engineering and technology, EAM, Automation, Field (computer science), Software asset management, Engineering management, Documentation, 020204 information systems, Machine learning, 0202 electrical engineering, electronic engineering, information engineering, [INFO]Computer Science [cs], NIST Enterprise Architecture Model, business, Literature survey
Abstract: Part 2: Model Derivation; International audience; In the era of digitalization, IT landscapes keep growing along with complexity and dependencies. This amplifies the need to determine the current elements of an IT landscape for the management and planning of IT landscapes as well as for failure analysis. The field of enterprise architecture documentation sought for more than a decade for solutions to minimize the manual effort to build enterprise architecture models or automation. We summarize the approaches presented in the last decade in a literature survey. Moreover, we present a novel, machine-learning based approach to detect and to identify applications in an IT landscape.
Published: 2018

22. Orbital and spectral analysis of the benchmark brown dwarf HD 4747B

Author: Anthony Boccaletti, Dino Mesa, Baptiste Lavie, Yves Magnard, Maud Langlois, Jean-Loup Baudino, Janis Hagelberg, Gael Chauvin, A-M. Lagrange, L. Weber, Sebastian Daemgen, Emmanuel Hugot, Arnaud Sevin, Michael R. Meyer, Stéphane Udry, Damien Ségransan, V. De Caprio, Alice Zurlo, Anthony Cheetham, Joany Andreina Manjarres Ramos, M. Carle, Raffaele Gratton, Francois Wildi, J. Pragt, Kevin Heng, Mickael Bonnefoy, Marcel Carbillet, C. Soenke, Matthias Samland, L. Gluck, François Ménard, T. Moulin, S. Peretti, T. O. B. Schmidt, P. Rabou, Arthur Vigan, Eric Stadler, H. Le Coroller, Valentina D'Orazi, Gérard Rousset, Silvano Desidera, Markus Janson, Markus Feldt, A. Pavlov, Anne-Lise Maire, Daniel Rouan, Observatoire Astronomique de l'Université de Genève (ObsGE), Université de Genève (UNIGE), Physikalisches Institut [Bern], Universität Bern [Bern], INAF - Osservatorio Astronomico di Padova (OAPD), Istituto Nazionale di Astrofisica (INAF), Max-Planck-Institut für Astronomie (MPIA), Max-Planck-Gesellschaft, Laboratoire d'Astrophysique de Marseille (LAM), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Aix Marseille Université (AMU)-Centre National d'Études Spatiales [Toulouse] (CNES), University of Oxford [Oxford], Laboratoire d'études spatiales et d'instrumentation en astrophysique (LESIA (UMR_8109)), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Department of Astronomy, Stockholm University, Institut de Planétologie et d'Astrophysique de Grenoble (IPAG), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Observatoire des Sciences de l'Univers de Grenoble (OSUG ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national des sciences de l'Univers (INSU - CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Center for Space and Habitability (CSH), University of Bern, Institute of Astronomy [ETH Zürich], Department of Physics [ETH Zürich] (D-PHYS), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Observatoire de Haute-Provence (OHP), Institut Pythéas (OSU PYTHEAS), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut de Recherche pour le Développement (IRD), Department of Biochemistry and Molecular Biology, Mayo Clinic, Department of Geriatric Medicine, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de Recherche Astrophysique de Lyon (CRAL), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS), Joseph Louis LAGRANGE (LAGRANGE), Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Observatoire de la Côte d'Azur, Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), INAF - Osservatorio Astronomico di Capodimonte (OAC), Bulgarian Academy of Sciences (BAS), NOVA Optical Infrared Instrumentation Group, University of Copenhagen = Københavns Universitet (KU), ESO, Physics Department [Garching], Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Université de Genève = University of Geneva (UNIGE), Universität Bern [Bern] (UNIBE), Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS), University of Oxford, Stockholm Observatory Department of Astronomy, Geneva Observatory, Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Centre National de la Recherche Scientifique (CNRS), Observatoire de Paris, Université Paris sciences et lettres (PSL), Laboratoire d'études spatiales et d'instrumentation en astrophysique = Laboratory of Space Studies and Instrumentation in Astrophysics (LESIA), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université de Lyon-Université de Lyon-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), 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 des sciences de l'Univers (INSU - CNRS)-Observatoire de la Côte d'Azur, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), University of Copenhagen = Københavns Universitet (UCPH), and Université Nice Sophia Antipolis (... - 2019) (UNS)
Subjects: [PHYS.ASTR.IM]Physics [physics]/Astrophysics [astro-ph]/Instrumentation and Methods for Astrophysic [astro-ph.IM], Brown dwarf, FOS: Physical sciences, Astrophysics, 01 natural sciences, Spectral line, Photometry (optics), Planet, 0103 physical sciences, Astrophysics::Solar and Stellar Astrophysics, Substellar object, 10. No inequality, 010303 astronomy & astrophysics, Astrophysics::Galaxy Astrophysics, ComputingMilieux_MISCELLANEOUS, Earth and Planetary Astrophysics (astro-ph.EP), Physics, [PHYS]Physics [physics], [SDU.ASTR]Sciences of the Universe [physics]/Astrophysics [astro-ph], 010308 nuclear & particles physics, Astronomy and Astrophysics, Effective temperature, Exoplanet, Radial velocity, 13. Climate action, Space and Planetary Science, Astrophysics::Earth and Planetary Astrophysics, [PHYS.ASTR]Physics [physics]/Astrophysics [astro-ph], Astrophysics - Earth and Planetary Astrophysics
Abstract: Context. The study of high-contrast imaged brown dwarfs and exoplanets depends strongly on evolutionary models. To estimate the mass of a directly imaged substellar object, its extracted photometry or spectrum is used and adjusted with model spectra together with the estimated age of the system. These models still need to be properly tested and constrained. HD 4747B is a brown dwarf close to the H burning mass limit, orbiting a nearby (d = 19.25 ± 0.58 pc), solar-type star (G9V); it has been observed with the radial velocity method for over almost two decades. Its companion was also recently detected by direct imaging, allowing a complete study of this particular object. Aims. We aim to fully characterize HD 4747B by combining a well-constrained dynamical mass and a study of its observed spectral features in order to test evolutionary models for substellar objects and to characterize its atmosphere. Methods. We combined the radial velocity measurements of High Resolution Echelle Spectrometer (HIRES) and CORALIE taken over two decades and high-contrast imaging of several epochs from NACO, NIRC2, and SPHERE to obtain a dynamical mass. From the SPHERE data we obtained a low-resolution spectrum of the companion from Y to H band, and two narrow band-width photometric measurements in the K band. A study of the primary star also allowed us to constrain the age of the system and its distance. Results. Thanks to the new SPHERE epoch and NACO archival data combined with previous imaging data and high-precision radial velocity measurements, we were able to derive a well-constrained orbit. The high eccentricity (e = 0.7362 ± 0.0025) of HD 4747B is confirmed, and the inclination and the semi-major axis are derived (i = 47.3 ± 1.6°, a = 10.01 ± 0.21 au). We derive a dynamical mass of mB = 70.0 ± 1.6 MJup, which is higher than a previous study but in better agreement with the models. By comparing the object with known brown dwarfs spectra, we derive a spectral type of L9 and an effective temperature of 1350 ± 50 K. With a retrieval analysis we constrain the oxygen and carbon abundances and compare them with the values from the HR 8799 planets.
Published: 2018

23. Investigation of the inner structures around HD169142 with VLT/SPHERE

Author: A. Pohl, Th. Henning, S. Peretti, Matthias Samland, Myriam Benisty, Sascha P. Quanz, Francois Menard, Anne-Lise Maire, J. de Boer, L. Weber, Philippe Delorme, Daniela Fantinel, Julien Girard, Ch. Ginski, Anthony Cheetham, Arthur Vigan, Paola Pinilla, Tomas Stolker, T. Fusco, Raphaël Galicher, T. Kopytova, Roxanne Ligi, Raffaele Gratton, Gael Chauvin, Silvano Desidera, Cecile Gry, Francois Wildi, Thibaut Moulin, Zahed Wahhaj, Markus Janson, M. Cudel, Beth Biller, Anne-Marie Lagrange, Marcos Suarez, H. LeCoroller, E. Sissa, M. Bonnefoy, M. Kasper, Joany Andreina Manjarres Ramos, C. Perrot, Maud Langlois, Dino Mesa, Tristan Buey, Michael Meyer, M. Feldt, A. Boccaletti, Alice Zurlo, J. L. Beuzit, M. Jaquet, D. Rouan, Laboratoire d'Astrophysique de Marseille (LAM), Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS), INAF - Osservatorio Astronomico di Padova (OAPD), Istituto Nazionale di Astrofisica (INAF), Leiden Observatory [Leiden], Universiteit Leiden, Institut de Planétologie et d'Astrophysique de Grenoble (IPAG), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Observatoire des Sciences de l'Univers de Grenoble (OSUG ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national des sciences de l'Univers (INSU - CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire d'études spatiales et d'instrumentation en astrophysique (LESIA (UMR_8109)), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institute of Astronomy [ETH Zürich], Department of Physics [ETH Zürich] (D-PHYS), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), University of Michigan [Ann Arbor], University of Michigan System, Max-Planck-Institut für Astronomie (MPIA), Max-Planck-Gesellschaft, Institute for Astronomy [Edinburgh] (IfA), University of Edinburgh, Observatoire Astronomique de l'Université de Genève (ObsGE), Université de Genève = University of Geneva (UNIGE), Sydney Institute for Astronomy (SIfA), The University of Sydney, European Southern Observatory [Santiago] (ESO), European Southern Observatory (ESO), Department of Astronomy, Stockholm University, ASU School of Earth and Space Exploration (SESE), Arizona State University [Tempe] (ASU), Ural Federal University [Ekaterinburg] (UrFU), Centre de Recherche Astrophysique de Lyon (CRAL), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), University of Arizona, Heidelberg University, Astronomical Institute Anton Pannekoek (AI PANNEKOEK), University of Amsterdam [Amsterdam] (UvA), Universidad Diego Portales [Santiago] (UDP), Millennium Nucleus Protoplanetary Disk, ONERA - The French Aerospace Lab [Châtillon], ONERA-Université Paris Saclay (COmUE), ANR-16-CE31-0013,PLANET-FORMING-DISKS,De meilleurs modèles pour de meilleures données(2016), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Aix Marseille Université (AMU)-Centre National d'Études Spatiales [Toulouse] (CNES), Universiteit Leiden [Leiden], Université de Genève (UNIGE), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS), Laboratoire d'interaction du rayonnement X avec la matière (LIXAM), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Stockholm Observatory Department of Astronomy, ESO, Physics Department [Garching], Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), IRD, Geneva Observatory, University of Geneva [Switzerland], Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Imagerie Tomographique et Radiothérapie, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), André, Cécile, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Technologie de Belfort-Montbeliard (UTBM), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Laboratoire d'Astrophysique de Grenoble (LAOG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), PSL Research University (PSL)-PSL Research University (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich)-Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Centre National d'Études Spatiales [Toulouse] (CNES)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire des Sciences de l'Univers de Grenoble (OSUG), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Technical University of Munich (TUM)-Technical University of Munich (TUM), Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-École normale supérieure - Lyon (ENS Lyon), and ONERA
Subjects: INDIVIDUAL, [SPI.OPTI] Engineering Sciences [physics]/Optics / Photonic, TELESCOPE, Infrared, FOS: Physical sciences, Astrophysics, Astrophysics::Cosmology and Extragalactic Astrophysics, OPTIQUE ADAPTATIVE, 01 natural sciences, law.invention, DETECTION, Telescope, Integral field spectrograph, Planet, law, 0103 physical sciences, TECHNIQUES, Astrophysics::Solar and Stellar Astrophysics, PLANETS AND SATELLITES, 010306 general physics, 010303 astronomy & astrophysics, Spectrograph, [PHYS.PHYS.PHYS-SPACE-PH] Physics [physics]/Physics [physics]/Space Physics [physics.space-ph], ComputingMilieux_MISCELLANEOUS, Astrophysics::Galaxy Astrophysics, HD169142, [SPI.SIGNAL] Engineering Sciences [physics]/Signal and Image processing, EXOPLANETE, Earth and Planetary Astrophysics (astro-ph.EP), Physics, [PHYS]Physics [physics], PROTOPLANETARY DISC, HIGH ANGULAR RESOLUTION, Astronomy and Astrophysics, Position angle, Exoplanet, FORMATION, [PHYS.PHYS.PHYS-SPACE-PH]Physics [physics]/Physics [physics]/Space Physics [physics.space-ph], Stars, Space and Planetary Science, [SPI.OPTI]Engineering Sciences [physics]/Optics / Photonic, Astrophysics::Earth and Planetary Astrophysics, [PHYS.ASTR]Physics [physics]/Astrophysics [astro-ph], [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, STARS, Astrophysics - Earth and Planetary Astrophysics
Abstract: We present observations of the Herbig Ae star HD169142 with VLT/SPHERE instruments InfraRed Dual-band Imager and Spectrograph (IRDIS) ($K1K2$ and $H2H3$ bands) and the Integral Field Spectrograph (IFS) ($Y$, $J$ and $H$ bands). We detect several bright blobs at $\sim$180 mas separation from the star, and a faint arc-like structure in the IFS data. Our reference differential imaging (RDI) data analysis also finds a bright ring at the same separation. We show, using a simulation based on polarized light data, that these blobs are actually part of the ring at 180 mas. These results demonstrate that the earlier detections of blobs in the $H$ and $K_S$ bands at these separations in Biller et al. as potential planet/substellar companions are actually tracing a bright ring with a Keplerian motion. Moreover, we detect in the images an additional bright structure at $\sim$93 mas separation and position angle of 355$^{\circ}$, at a location very close to previous detections. It appears point-like in the $YJ$ and $K$ bands but is more extended in the $H$ band. We also marginally detect an inner ring in the RDI data at $\sim$100 mas. Follow-up observations are necessary to confirm the detection and the nature of this source and structure., 11 pages, 7 figures, 2 tables; published in MNRAS (this version includes proofs corrections)
Published: 2018

24. Fluorescence-guided surgery and intervention - An AAPM emerging technology blue paper

Author: Arjun G. Yodh, Robert J. Nordstrom, Brian C. Wilson, Heidrun Wabnitz, Bruce J. Tromberg, Yu Chen, Timothy C. Zhu, Vasilis Ntziachristos, Maritoni Litorja, Sylvain Gioux, T. Joshua Pfefer, Brian W. Pogue, Keith D. Paulsen, Institute for Biological and Medical Imaging (IBMI), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz-Zentrum München (HZM), Department of Biology, Stanford University, Stanford University, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz Zentrum München = German Research Center for Environmental Health, École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et nanosciences d'Alsace (FMNGE), Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, and Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)
Subjects: Computer science, Psychological intervention, 030218 nuclear medicine & medical imaging, Presentation, 0302 clinical medicine, Computer-Assisted, resection, Societies, Medical, intervention, ComputingMilieux_MISCELLANEOUS, media_common, screening and diagnosis, Optical Imaging, imaging, General Medicine, imaging system, 3. Good health, Other Physical Sciences, Detection, Nuclear Medicine & Medical Imaging, Surgery, Computer-Assisted, 030220 oncology & carcinogenesis, Practice Guidelines as Topic, Biomedical Imaging, Curriculum, Patient Safety, molecular probe, medicine.medical_specialty, Consensus, Emerging technologies, media_common.quotation_subject, Health Personnel, Oncology and Carcinogenesis, Biomedical Engineering, Bioengineering, 03 medical and health sciences, Optical imaging, Medical, medicine, Humans, molecular, Special Report, Imaging, Imaging System, Intervention, Molecular, Molecular Probe, Resection, Surgery, 4.1 Discovery and preclinical testing of markers and technologies, Intervention (law), Imaging technology, [SPI.OPTI]Engineering Sciences [physics]/Optics / Photonic, Societies
Abstract: Fluorescence-guided surgery (FGS) and other interventions are rapidly evolving as a class of technologically driven interventional approaches in which many surgical specialties visualize fluorescent molecular tracers or biomarkers through associated cameras or oculars to guide clinical decisions on pathological lesion detection and excision/ablation. The technology has been commercialized for some specific applications, but also presents technical challenges unique to optical imaging that could confound the utility of some interventional procedures where real-time decisions must be made. Accordingly, the AAPM has initiated the publication of this Blue Paper of The Emerging Technology Working Group (TETAWG) and the creation of a Task Group from the Therapy Physics Committee within the Treatment Delivery Subcommittee. In describing the relevant issues, this document outlines the key parameters, stakeholders, impacts, and outcomes of clinical FGS technology and its applications. The presentation is not intended to be conclusive, but rather to inform the field of medical physics and stimulate the discussions needed in the field with respect to a seemingly low-risk imaging technology that has high potential for significant therapeutic impact. This AAPM Task Group is working toward consensus around guidelines and standards for advancing the field safely and effectively.
Published: 2018

25. Solver comparison for Poisson-like equations on tokamak geometries

Author: Bourne, Emily, Leleux, Philippe, Kormann, Katharina, Kruse, Carola, Grandgirard, Virginie, Güclü, Yaman, Kühn, Martin Joachim, Rüde, Ulrich, Sonnendrücker, Eric, Zoni, Edoardo, CEA Cadarache, Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Européen de Recherche et de Formation Avancée en Calcul Scientifique (CERFACS), Ruhr-Universität Bochum, Fakultät für Mathematik, Universitätsstr. 150, 44801 Bochum, Germany, Ruhr-Universität Bochum [Bochum], Max-Planck-Institut für Plasmaphysik [Garching] (IPP), German Aerospace Center (DLR), Department Mathematik [Erlangen], Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Lawrence Berkeley National Laboratory [Berkeley] (LBNL), 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), CERFACS [Toulouse], Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre Européen de Recherche et de Formation Avancée en Calcul Scientifique - CERFACS (CERFACS), and Bourne, Emily
Subjects: Numerical Analysis, multigrid scheme, Physics and Astronomy (miscellaneous), plasma simulation, finite differences, Applied Mathematics, [MATH.MATH-NA] Mathematics [math]/Numerical Analysis [math.NA], Poisson equation, Computer Science Applications, Computational Mathematics, [MATH.MATH-MP]Mathematics [math]/Mathematical Physics [math-ph], [PHYS.PHYS.PHYS-PLASM-PH]Physics [physics]/Physics [physics]/Plasma Physics [physics.plasm-ph], [PHYS.PHYS.PHYS-PLASM-PH] Physics [physics]/Physics [physics]/Plasma Physics [physics.plasm-ph], Modeling and Simulation, finite elements, conjugate gradient, [MATH.MATH-MP] Mathematics [math]/Mathematical Physics [math-ph], tokamak, [MATH.MATH-NA]Mathematics [math]/Numerical Analysis [math.NA], finite volumes
Abstract: The solution of Poisson-like equations defined on complex geometry is required for gyrokinetic simulations, which are important for the modelling of plasma turbulence in nuclear fusion devices such as the ITER tokamak. In this paper, we compare three solvers capable of solving this problem, in terms of the accuracy of the solution, and their computational efficiency. The first, the Spline FEM solver, uses C 1 polar splines to construct a finite elements method which solves the equation on curvilinear coordinates. The resulting linear system is solved using a conjugate gradient method. The second, the GmgPolar solver, uses a symmetric finite differences method to discretise the differential equation. The resulting linear system is solved using a tailored geometric multigrid scheme, with a combination of zebra circle and radial line smoothers, together with an implicit extrapolation scheme. The third, the Embedded Boundary solver, uses a finite volumes method on Cartesian coordinates with an embedded boundary scheme. The resulting linear system is solved using a multigrid scheme. The Spline FEM solver is shown to be the most accurate. The GmgPolar solver is shown to use the least memory. The Embedded Boundary solver is shown to be the fastest in most cases. All three solvers are shown to be capable of solving the equation on a realistic non-analytical geometry. The Embedded Boundary solver is additionally used to attempt to solve an X-point geometry, highlighting the problems with concave boundaries.
Published: 2023

26. CHRAC/ACF Contribute to the Repressive Ground State of Chromatin

Author: Xu Zhang, Dhawal Jain, Frank Schnorrer, Alessandro Scacchetti, Peter B. Becker, Bas van Steensel, Laura Brueckner, Tamas Schauer, Tobias Straub, Center for Integrated Protein Science (CIPSM), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU)-Helmholtz Zentrum München = German Research Center for Environmental Health, Institut des Sciences Chimiques de Rennes (ISCR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), U54 DK107965, National Institutes of Health, MSCA-ITN-2014-ETN No. 642934, European Research Council (ERC), FP/2007–2013, ERC, CNRSExcellence Initiative Aix-Marseille University AMIDEXANRLabEX-INFORM, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz-Zentrum München (HZM)-Ludwig Maximilian University of Munich [Germany] (LMU München), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Ecole Nationale Supérieure de Chimie de Rennes (ENSCR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), and Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)
Subjects: 0301 basic medicine, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], Plant Science, Biology, Biochemistry, Genetics and Molecular Biology (miscellaneous), Chromatin remodeling, Transcriptome, 03 medical and health sciences, 0302 clinical medicine, Transcription (biology), Gene expression, Nucleosome, Gene, ChIA-PET, Research Articles, 030304 developmental biology, Genetics, 0303 health sciences, Reporter gene, Ecology, biology.organism_classification, Chromatin, Cell biology, 030104 developmental biology, Drosophila melanogaster, 030217 neurology & neurosurgery, Research Article
Abstract: Chromatin accessibility complex/ATP-utilizing chromatin assembly and remodeling factor help to establish basal transcriptional repression, conceivably through improving the regular spacing of nucleosomes in euchromatin., The chromatin remodeling complexes chromatin accessibility complex and ATP-utilizing chromatin assembly and remodeling factor (ACF) combine the ATPase ISWI with the signature subunit ACF1. These enzymes catalyze well-studied nucleosome sliding reactions in vitro, but how their actions affect physiological gene expression remains unclear. Here, we explored the influence of Drosophila melanogaster chromatin accessibility complex/ACF on transcription by using complementary gain- and loss-of-function approaches. Targeting ACF1 to multiple reporter genes inserted at many different genomic locations revealed a context-dependent inactivation of poorly transcribed reporters in repressive chromatin. Accordingly, single-embryo transcriptome analysis of an Acf knock-out allele showed that only lowly expressed genes are derepressed in the absence of ACF1. Finally, the nucleosome arrays in Acf-deficient chromatin show loss of physiological regularity, particularly in transcriptionally inactive domains. Taken together, our results highlight that ACF1-containing remodeling factors contribute to the establishment of an inactive ground state of the genome through chromatin organization.
Published: 2017
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27. Identification of novel risk loci for restless legs syndrome in genome-wide association studies in individuals of European ancestry: a meta-analysis

Author: Schormair, Barbara, Zhao, Chen, Bell, Steven, Tilch, Erik, Salminen, Aaro V., Pütz, Benno, Dauvilliers, Yves, Stefani, Ambra, Högl, Birgit, Poewe, Werner, Kemlink, David, Sonka, Karel, Bachmann, Cornelius G., Paulus, Walter, Trenkwalder, Claudia, Oertel, Wolfgang H., Hornyak, Magdolna, Teder-Laving, Maris, Metspalu, Andres, Hadjigeorgiou, Georgios M., Polo, Olli, Fietze, Ingo, Ross, Owen A., Wszolek, Zbigniew, Butterworth, Adam S., Soranzo, Nicole, Ouwehand, Willem H., Roberts, David J., Danesh, John, Allen, Richard P., Earley, Christopher J., Ondo, William G., Xiong, Lan, Montplaisir, Jacques, Gan-Or, Ziv, Perola, Markus, Vodicka, Pavel, Dina, Christian, Franke, Andre, Tittmann, Lukas, Stewart, Alexandre F. R., Shah, Svati H., Gieger, Christian, Peters, Annette, Rouleau, Guy A., Berger, Klaus, Oexle, Konrad, Di Angelantonio, Emanuele, Hinds, David A., Müller-Myhsok, Bertram, Winkelmann, Juliane, Team, 23andMe Research, group, DESIR, Institute of Human Genetics, Technische Universität München [München] (TUM), Technische Universität München [München] (TUM)-German Research Center for Environmental Health-Helmholtz-Zentrum München (HZM), Statistical Genetics Group, Metacohorts Consortium, Neuropsychiatrie : recherche épidémiologique et clinique, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Department of Neurology, Innsbruck Medical University [Austria] (IMU), Charles University [Prague]-1st Faculty of Medicine, First Faculty of Medicine and General Teaching Hospital [Prague, Czech Republic], Charles university in Prague (CZECH REPUBLIC), Department of Clinical Neurophysiology [Göttingen], Georg-August-University [Göttingen], Paracelsus Elena Klinik, Centre for Parkinson's Disease & Movement Disorders, University of Tartu, Sleep Research Unit, University of Turku, Department of Pulmonary Medicine, Tampere University Hospital, Interdisciplinary Center of Sleep Medicine, Universitätsmedizin Berlin-Internetseiten der Charité, Centre for Molecular Medicine and Therapeutics, University of British Columbia (UBC), Department of Public Health & Primary Care, University of Cambridge [UK] (CAM), The Wellcome Trust Sanger Institute [Cambridge], Center of Excellence in Neuroscience, CHU de Montréal, Hôpital du Sacré-Coeur de Montréal, Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki-University of Helsinki, Department of Chronic Disease Prevention, National Institute for Health and Welfare [Helsinki], Institute of Experimental Medicine, Czech Academy of Sciences [Prague] (ASCR), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institute for Clinical Molecular Biology, Christian-Albrechts-Universität zu Kiel (CAU), Center For Narcolepsy, Stanford University [Stanford], Center of Excellence in Neuromics, University of Montreal, Institute of Human Genetics, Technische Universität München, Translational Centre for Regenerative Medicine (TRM), Department of Cell Therapy, Universität Leipzig [Leipzig]-Universität Leipzig [Leipzig], Bell, Steven [0000-0001-6774-3149], Butterworth, Adam [0000-0002-6915-9015], Soranzo, Nicole [0000-0003-1095-3852], Ouwehand, Willem [0000-0002-7744-1790], Danesh, John [0000-0003-1158-6791], Di Angelantonio, Emanuele [0000-0001-8776-6719], Apollo - University of Cambridge Repository, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz-Zentrum München (HZM)-German Research Center for Environmental Health, Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Charles University [Prague] (CU)-1st Faculty of Medicine, Charles University [Prague] (CU), Czech Academy of Sciences [Prague] (CAS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Stanford University, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-German Research Center for Environmental Health-Helmholtz-Zentrum München (HZM), and Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: DNA-Binding Proteins, Restless Legs Syndrome, [SDV]Life Sciences [q-bio], European Continental Ancestry Group, Humans, Genetic Predisposition to Disease, Nerve Tissue Proteins, Semaphorins, GPI-Linked Proteins, Transcription Factors, Genome-Wide Association Study
Abstract: International audience; BACKGROUND: Restless legs syndrome is a prevalent chronic neurological disorder with potentially severe mental and physical health consequences. Clearer understanding of the underlying pathophysiology is needed to improve treatment options. We did a meta-analysis of genome-wide association studies (GWASs) to identify potential molecular targets. METHODS: In the discovery stage, we combined three GWAS datasets (EU-RLS GENE, INTERVAL, and 23andMe) with diagnosis data collected from 2003 to 2017, in face-to-face interviews or via questionnaires, and involving 15 126 cases and 95 725 controls of European ancestry. We identified common variants by fixed-effect inverse-variance meta-analysis. Significant genome-wide signals (p≤5 × 10(-8)) were tested for replication in an independent GWAS of 30 770 cases and 286 913 controls, followed by a joint analysis of the discovery and replication stages. We did gene annotation, pathway, and gene-set-enrichment analyses and studied the genetic correlations between restless legs syndrome and traits of interest. FINDINGS: We identified and replicated 13 new risk loci for restless legs syndrome and confirmed the previously identified six risk loci. MEIS1 was confirmed as the strongest genetic risk factor for restless legs syndrome (odds ratio 1·92, 95% CI 1·85-1·99). Gene prioritisation, enrichment, and genetic correlation analyses showed that identified pathways were related to neurodevelopment and highlighted genes linked to axon guidance (associated with SEMA6D), synapse formation (NTNG1), and neuronal specification (HOXB cluster family and MYT1). INTERPRETATION: Identification of new candidate genes and associated pathways will inform future functional research. Advances in understanding of the molecular mechanisms that underlie restless legs syndrome could lead to new treatment options. We focused on common variants; thus, additional studies are needed to dissect the roles of rare and structural variations. FUNDING: Deutsche Forschungsgemeinschaft, Helmholtz Zentrum München-Deutsches Forschungszentrum für Gesundheit und Umwelt, National Research Institutions, NHS Blood and Transplant, National Institute for Health Research, British Heart Foundation, European Commission, European Research Council, National Institutes of Health, National Institute of Neurological Disorders and Stroke, NIH Research Cambridge Biomedical Research Centre, and UK Medical Research Council.
Published: 2017

28. Chromosome topology guides the Drosophila Dosage Compensation Complex for target gene activation

Author: Peter B. Becker, Christian Albig, Yad Ghavi-Helm, Giacomo Cavalli, Tom Sexton, Tamas Schauer, Eileen E. M. Furlong, Catherine Regnard, Center for Integrated Protein Science (CIPSM), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig Maximilian University of Munich [Germany] (LMU München)-Helmholtz-Zentrum München (HZM), European Molecular Biology Laboratory, Genome Biology Unit, Heidelberg, Germany., Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM), and Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz-Zentrum München (HZM)-Ludwig Maximilian University of Munich [Germany] (LMU München)
Subjects: 0301 basic medicine, Genetics, Regulation of gene expression, [SDV.GEN]Life Sciences [q-bio]/Genetics, Dosage compensation, [SDV]Life Sciences [q-bio], fungi, Chromosome, Articles, Biology, Biochemistry, Dosage compensation complex, Chromatin, nuclear architecture, Chromosome conformation capture, 03 medical and health sciences, 030104 developmental biology, chromatin, chromosome conformation capture, Molecular Biology, Gene, X chromosome
Abstract: International audience; X chromosome dosage compensation in Drosophila requires chromosome-wide coordination of gene activation. The male-specific lethal dosage compensation complex (DCC) identifies and binds to X-chromosomal high-affinity sites (HAS) from which it boosts transcription. A sub-class of HAS, PionX sites, represent first contacts on the X. Here, we explored the chromosomal interactions of representative PionX sites by high-resolution 4C and determined the global chromosome conformation by Hi-C in sex-sorted embryos. Male and female X chromosomes display similar nuclear architecture, concordant with clustered, constitutively active genes. PionX sites, like HAS, are evenly distributed in the active compartment and engage in short- and long-range interactions beyond compartment boundaries. Long-range, inter-domain interactions between DCC binding sites are stronger in males, suggesting that the complex refines chromatin organization. By de novo induction of DCC in female cells, we monitored the extent of activation surrounding PionX sites. This revealed a remarkable range of DCC action not only in linear proximity, but also at megabase distance if close in space, suggesting that DCC profits from pre-existing chromosome folding to activate genes.
Published: 2017

29. Quantum dynamics of H 2 in a carbon nanotube: Separation of time scales and resonance enhanced tunneling

Author: Uwe Manthe, Fermín Huarte-Larrañaga, Manel Mondelo-Martell, Theoretische Chemie, TU Munchen, Germany, Department of Chemistry, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), and Universitat de Barcelona
Subjects: Nanotube, Quantum dynamics, Diffusion, Diabatic, General Physics and Astronomy, Nanotechnology, 010402 general chemistry, 01 natural sciences, Molecular physics, Adiabatic theorem, Correlation function, MCTDH, 0103 physical sciences, Teoria quàntica, Physical and Theoretical Chemistry, Carboni, Quantum tunnelling, ComputingMilieux_MISCELLANEOUS, Physics, Nanotubes, 010304 chemical physics, Carbon, 0104 chemical sciences, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, Quantum dot, Quantum theory, [PHYS.PHYS.PHYS-CHEM-PH]Physics [physics]/Physics [physics]/Chemical Physics [physics.chem-ph], Nanotubs
Abstract: Quantum confinement effects are known to affect the behavior of molecules adsorbed in nanostructured materials. In order to study these effects on the transport of a single molecule through a nanotube, we present a quantum dynamics study on the diffusion of H-2 in a narrow (8,0) carbon nanotube in the low pressure limit. Transmission coefficients for the elementary step of the transport process are calculated using the flux correlation function approach and diffusion rates are obtained using the single hopping model. The different time scales associated with the motion in the confined coordinates and the motion along the nanotube's axis are utilized to develop an efficient and numerically exact approach, in which a diabatic basis describing the fast motion in the confined coordinate is employed. Furthermore, an adiabatic approximation separating the dynamics of confined and unbound coordinates is studied. The results obtained within the adiabatic approximation agree almost perfectly with the numerically exact ones. The approaches allow us to accurately study the system's dynamics on the picosecond time scale and resolve resonance structures present in the transmission coefficients. Resonance enhanced tunneling is found to be the dominant transport mechanism at low energies. Comparison with results obtained using transition state theory shows that tunneling significantly increases the diffusion rate at T < 120 K. Published by AIP Publishing.
Published: 2017

30. Recombinant tandem of pore-domains in a Weakly Inward rectifying K+ channel 2 (TWIK2) forms active lysosomal channels

Author: Bobak, Nicole, Feliciangeli, Sylvain, Chen, Cheng-Chang, Ben Soussia, Ismail, Bittner, Stefan, Pagnotta, Sophie, Ruck, Tobias, Biel, Martin, Wahl-Schott, Christian, Grimm, Christian, Meuth, Sven G., Lesage, Florian, Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Center for Integrated Protein Science (CIPSM), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz-Zentrum München (HZM)-Ludwig Maximilian University of Munich [Germany] (LMU München), University Medical Center of the Johannes Gutenberg University Mainz, Centre Commun de Microscopie Appliquée (CCMA), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), University of Münster, and Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig Maximilian University of Munich [Germany] (LMU München)-Helmholtz-Zentrum München (HZM)
Subjects: Science, [SDV]Life Sciences [q-bio], Gene Expression, Article, Recombinant Proteins, Madin Darby Canine Kidney Cells, Rats, Mice, Protein Transport, Dogs, HEK293 Cells, Potassium Channels, Tandem Pore Domain, Animals, Humans, Medicine, Protein Interaction Domains and Motifs, Amino Acid Sequence, Protein Multimerization, Lysosomes
Abstract: International audience; Recombinant TWIK2 channels produce weak basal background K+ currents. Current amplitudes depend on the animal species the channels have been isolated from and on the heterologous system used for their re-expression. Here we show that this variability is due to a unique cellular trafficking. We identified three different sequence signals responsible for the preferential expression of TWIK2 in the Lamp1-positive lysosomal compartment. Sequential inactivation of tyrosine-based (Y308ASIP) and di-leucine-like (E266LILL and D282EDDQVDIL) trafficking motifs progressively abolishes the targeting of TWIK2 to lysosomes, and promotes its functional relocation at the plasma membrane. In addition, TWIK2 contains two N-glycosylation sites (N79AS and N85AS) on its luminal side, and glycosylation is necessary for expression in lysosomes. As shown by electrophysiology and electron microscopy, TWIK2 produces functional background K+ currents in the endolysosomes, and its expression affects the number and mean size of the lysosomes. These results show that TWIK2 is expressed in lysosomes, further expanding the registry of ion channels expressed in these organelles.
Published: 2017

31. Shadows and spirals in the protoplanetary disk HD 100453

Author: C. Fontanive, Alice Zurlo, Christian Ginski, Thomas Henning, Paola Pinilla, Tomas Stolker, M. Llored, Maud Langlois, D. Gisler, O. Moeller-Nilsson, R. van Boekel, J. Pragt, Yves Magnard, Kevin Wagner, François Ménard, Jean-François Sauvage, Silvano Desidera, Antonio Garufi, David Mouillet, Geoffroy Lesur, Francois Wildi, M. Bonnefoy, Myriam Benisty, T. Buey, Raffaele Gratton, Arthur Vigan, Gael Chauvin, Anthony Boccaletti, Michiel Min, A-M. Lagrange, Jacopo Antichi, Thierry Fusco, Markus Feldt, Christophe Pinte, H. LeCoroller, Carsten Dominik, Jean-Luc Beuzit, M. Cudel, E. Sissa, Dino Mesa, J. de Boer, Attila Juhasz, Ronald Roelfsema, Cornelis P. Dullemond, M. Kasper, Stefano Facchini, Adriana Pohl, Daniel Apai, Sascha P. Quanz, Institut de Planétologie et d'Astrophysique de Grenoble (IPAG), Centre National d'Études Spatiales [Toulouse] (CNES)-Observatoire des Sciences de l'Univers de Grenoble (OSUG ), Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Météo-France -Institut national des sciences de l'Univers (INSU - CNRS)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA)-Météo-France, Astronomical Institute Anton Pannekoek, University of Amsterdam, Max-Planck-Institut für Astronomie (MPIA), Leiden Observatory, Institute of Earth Sciences, Heidelberg University, Centre de Recherche Astrophysique de Lyon (CRAL), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Astrophysique de Marseille (LAM), Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS), SRON Netherlands Institute for Space Research, Department of Astronomy, Steward Observatory, Institute of Astronomy, Madingley Road, Cambridge CB3, OHA, UK, Max-Planck-Institut fur extraterrestrische Physik, Universidad Autononoma de Madrid, Dpto. Fisica Teorica, Facultad de Ciencias, Campus de Cantoblanco, 28049, Madrid, Spain, Institute for Astronomy, Department of Physics, ETH Zürich, Nucleo de Astronomia, Facultad de Ingenieria, Universidad Diego Portales, Av. Ejercito 441, Santiago, Chile, Laboratoire d'études spatiales et d'instrumentation en astrophysique (LESIA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), INAF-Osservatorio Astronomico di Padova, Institute for Astronomy, Blackford Hill, European Southern Observatory (ESO), INAF-Osservatorio Astrofisico di Arcetri (INAF-OAA), ONERA, Geneva Observatory, Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Observatoire des Sciences de l'Univers de Grenoble (OSUG ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national des sciences de l'Univers (INSU - CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Astronomical Institute Anton Pannekoek (AI PANNEKOEK), University of Amsterdam [Amsterdam] (UvA), Max-Planck-Gesellschaft, Leiden Observatory [Leiden], Universiteit Leiden, Institute for Theoretical Astrophysics [Heidelberg], Heidelberg University, École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), SRON Netherlands Institute for Space Research (SRON), Steward Observatory (STEWARD OBSERVATORY), University of Arizona, Institute of Astronomy [Cambridge], University of Cambridge [UK] (CAM), Max-Planck-Institut für Extraterrestrische Physik (MPE), Universidad Autonónoma de Madrid, Institute of Astronomy [ETH Zürich], Department of Physics [ETH Zürich] (D-PHYS), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Universidad Diego Portales [Santiago] (UDP), Universidade do Chile, INAF - Osservatorio Astronomico di Padova (OAPD), Istituto Nazionale di Astrofisica (INAF), Institute for Astronomy [Edinburgh] (IfA), University of Edinburgh, ESO, Physics Department [Garching], Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), ONERA - The French Aerospace Lab [Châtillon], ONERA-Université Paris Saclay (COmUE), Kiepenheuer-Institut für Sonnenphysik (KIS), Université de Genève = University of Geneva (UNIGE), Universiteit Leiden [Leiden], Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS), University of Geneva [Switzerland], Centre National d'Études Spatiales [Toulouse] (CNES)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire des Sciences de l'Univers de Grenoble (OSUG), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich)-Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Observatoire de Paris, PSL Research University (PSL)-PSL Research University (PSL)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Technical University of Munich (TUM)-Technical University of Munich (TUM), Low Energy Astrophysics (API, FNWI), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Aix Marseille Université (AMU)-Centre National d'Études Spatiales [Toulouse] (CNES), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)
Subjects: Brightness, FOS: Physical sciences, Astrophysics, RADIATIVE TRANSFER, Astrophysics::Cosmology and Extragalactic Astrophysics, Protoplanetary disk, OPTIQUE ADAPTATIVE, 01 natural sciences, VLT, POLARIMETRIE, POLARIMETRIC, Planet, SPHERE, 0103 physical sciences, TECHNIQUES, 010303 astronomy & astrophysics, Astrophysics::Galaxy Astrophysics, Physics, Earth and Planetary Astrophysics (astro-ph.EP), Inclined orbit, Spiral galaxy, 010308 nuclear & particles physics, Scattering, protoplanetary disks, Astronomy and Astrophysics, Scale height, TRANSFERT RADIATIF, Wavelength, techniques: polarimetric, Space and Planetary Science, [SDU]Sciences of the Universe [physics], [SPI.OPTI]Engineering Sciences [physics]/Optics / Photonic, Astrophysics::Earth and Planetary Astrophysics, [PHYS.ASTR]Physics [physics]/Astrophysics [astro-ph], [SPI.SIGNAL]Engineering Sciences [physics]/Signal and Image processing, Astrophysics - Earth and Planetary Astrophysics
Abstract: Understanding the diversity of planets requires to study the morphology and the physical conditions in the protoplanetary disks in which they form. We observed and spatially resolved the disk around the ~10 Myr old protoplanetary disk HD 100453 in polarized scattered light with SPHERE/VLT at optical and near-infrared wavelengths, reaching an angular resolution of ~0.02", and an inner working angle of ~0.09". We detect polarized scattered light up to ~0.42" (~48 au) and detect a cavity, a rim with azimuthal brightness variations at an inclination of 38 degrees, two shadows and two symmetric spiral arms. The spiral arms originate near the location of the shadows, close to the semi major axis. We detect a faint spiral-like feature in the SW that can be interpreted as the scattering surface of the bottom side of the disk, if the disk is tidally truncated by the M-dwarf companion currently seen at a projected distance of ~119 au. We construct a radiative transfer model that accounts for the main characteristics of the features with an inner and outer disk misaligned by ~72 degrees. The azimuthal brightness variations along the rim are well reproduced with the scattering phase function of the model. While spirals can be triggered by the tidal interaction with the companion, the close proximity of the spirals to the shadows suggests that the shadows could also play a role. The change in stellar illumination along the rim, induces an azimuthal variation of the scale height that can contribute to the brightness variations. Dark regions in polarized images of transition disks are now detected in a handful of disks and often interpreted as shadows due to a misaligned inner disk. The origin of such a misalignment in HD 100453, and of the spirals, is unclear, and might be due to a yet-undetected massive companion inside the cavity, and on an inclined orbit., Comment: A&A, accepted
Published: 2017

32. Biallelic Mutations in LIPT2 Cause a Mitochondrial Lipoylation Defect Associated with Severe Neonatal Encephalopathy

Author: Audrey Boutron, Florence Habarou, Nathalie Boddaert, Tobias B. Haack, Johannes A. Mayr, Richard J. Rodenburg, G. Christoph Korenke, Chris Ottolenghi, Coraline Grisel, Holger Prokisch, Dominique Chretien, Christine Bole-Feysot, Stefan Kölker, Agnès Delahodde, Ivan Nemazanyy, Monika Eisermann, Thomas Meitinger, Nicolas Goudin, Agnès Rötig, Robert Barouki, Iris Marquardt, Marine Madrange, Patrick Nitschke, Pascale de Lonlay, Clément Pontoizeau, Yamina Hamel, Tim M. Strom, Elise Lebigot, Cécile Laroche, René G. Feichtinger, Bernadette Chadefaux-Vekemans, Kanetee Busiah, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Eurecom [Sophia Antipolis], ISA NMR Methods for Metabolism - Methodes RMN en métabolomique (2014-2018), Institut des Sciences Analytiques (ISA), Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Epilepsies de l'Enfant et Plasticité Cérébrale (U1129), 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), Dept Biochem, Universidade Federal de Pernambuco [Recife] (UFPE), Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (PROTECT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Biochimie Métabolique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme de génomique [SFR Necker], Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Plate Forme Paris Descartes de Bioinformatique (BIP-D), Université Paris Descartes - Paris 5 (UPD5), Plateforme d'Imagerie Cellulaire [SFR Necker], Service de Radiologie et imagerie médicale [CHU Necker], Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Fonctions et dysfonctions de la mitochondrie (FDMITO), Département Biologie Cellulaire (BioCell), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Division of Inherited Metabolic Diseases, University Children's Hospital Heidelberg, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Helmholtz-Zentrum München (HZM), Institute of Human Genetics, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-German Research Center for Environmental Health-Helmholtz-Zentrum München (HZM), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biochimie métabolique [CHU Necker], Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Service de Biochimie [CHU Bicêtre], AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), NMR Methods for Metabolism - Methodes RMN en métabolomique, Centre National de la Recherche Scientifique (CNRS)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École normale supérieure - Lyon (ENS Lyon)-Centre National de la Recherche Scientifique (CNRS)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École normale supérieure - Lyon (ENS Lyon), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay, Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Institut de Biologie Intégrative de la Cellule (I2BC), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay, Technical University of Munich (TUM), Technische Universität München [München] (TUM)-Helmholtz-Zentrum München (HZM)-German Research Center for Environmental Health, CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz-Zentrum München (HZM)-German Research Center for Environmental Health, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Helmholtz Zentrum München = German Research Center for Environmental Health, and Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz Zentrum München = German Research Center for Environmental Health
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Dehydrogenase, chemistry.chemical_compound, 0302 clinical medicine, Amino Acids, Genetics (clinical), Cells, Cultured, Brain Diseases, Brain Mapping, Glycine cleavage system, Thioctic Acid, Brain, Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6], Pyruvate dehydrogenase complex, encephalopathy, metabolic flux, Magnetic Resonance Imaging, 3. Good health, Mitochondria, Lipoic acid, Biochemistry, α-oxoglutarate dehydrogenase, Leucine, Protein Binding, medicine.medical_specialty, Lipoylation, Glycine, Biology, 03 medical and health sciences, Oxygen Consumption, pyruvate dehydrogenase, Internal medicine, Report, Genetics, medicine, LIPT2, Humans, hyperglycinemia, Infant, Newborn, Lipt2, Encephalopathy, Hyperglycinemia, Lipoic Acid, Metabolic Flux, Pyruvate Dehydrogenase, α-oxoglutarate Dehydrogenase, lipoic acid, 030104 developmental biology, Endocrinology, chemistry, Atrophy, Branched-chain alpha-keto acid dehydrogenase complex, Energy Metabolism, 030217 neurology & neurosurgery, Acyltransferases, Protein lipoylation
Abstract: Item does not contain fulltext Lipoate serves as a cofactor for the glycine cleavage system (GCS) and four 2-oxoacid dehydrogenases functioning in energy metabolism (alpha-oxoglutarate dehydrogenase [alpha-KGDHc] and pyruvate dehydrogenase [PDHc]), or amino acid metabolism (branched-chain oxoacid dehydrogenase, 2-oxoadipate dehydrogenase). Mitochondrial lipoate synthesis involves three enzymatic steps catalyzed sequentially by lipoyl(octanoyl) transferase 2 (LIPT2), lipoic acid synthetase (LIAS), and lipoyltransferase 1 (LIPT1). Mutations in LIAS have been associated with nonketotic hyperglycinemia-like early-onset convulsions and encephalopathy combined with a defect in mitochondrial energy metabolism. LIPT1 deficiency spares GCS deficiency and has been associated with a biochemical signature of combined 2-oxoacid dehydrogenase deficiency leading to early death or Leigh-like encephalopathy. We report on the identification of biallelic LIPT2 mutations in three affected individuals from two families with severe neonatal encephalopathy. Brain MRI showed major cortical atrophy with white matter abnormalities and cysts. Plasma glycine was mildly increased. Affected individuals' fibroblasts showed reduced oxygen consumption rates, PDHc, alpha-KGDHc activities, leucine catabolic flux, and decreased protein lipoylation. A normalization of lipoylation was observed after expression of wild-type LIPT2, arguing for LIPT2 requirement in intramitochondrial lipoate synthesis. Lipoic acid supplementation did not improve clinical condition nor activities of PDHc, alpha-KGDHc, or leucine metabolism in fibroblasts and was ineffective in yeast deleted for the orthologous LIP2.
Published: 2017

33. The cryo-EM structure of a ribosome–Ski2-Ski3-Ski8 helicase complex

Author: Christian Schmidt, Markus Pech, Alain Jacquier, Katharina Braunger, Quentin Defenouillère, Micheline Fromont-Racine, Vivekanandan Shanmuganathan, André Heuer, Roland Beckmann, Abdelkader Namane, Elena Conti, Thomas Becker, Otto Berninghausen, Eva Kowalinski, Center for Integrated Protein Science (CIPSM), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU)-Helmholtz Zentrum München = German Research Center for Environmental Health, Max-Planck-Institut für Biochemie = Max Planck Institute of Biochemistry (MPIB), Max-Planck-Gesellschaft, Génétique des Interactions macromoléculaires / Genetics of Macromolecular Interactions, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), ED 515 - Complexité du vivant, Université Pierre et Marie Curie - Paris 6 (UPMC), We thank the Leibnitz-Rechenzentrum Munich (LRZ) for providing computational services and support. This work was supported by the German Research Council (SFB646 to R.B, T.B., and E.C., GRK1721 to R.B. and E.C., FOR1805 to R.B, and SFB1035 to E.C), by the Max Planck Gesellschaft (E.C.), and by the Agence Nationale de la Recherche (2011-BSV6-011-02 and ANR-14-CE-10-0014-01 to Q.D., A.J., and M.F.-R.). R.B. and E.C. acknowledge support by the Center for Integrated Protein Science Munich (CiPS-M), the Graduate School of Quantitative Biosciences Munich (QBM), and the European Research Council (Advanced Grants CRYOTRANSLATION and DEAD2THEEND). We also acknowledge the support of Ph.D. and postdoctoral fellowships from Boehringer Ingelheim Fonds (to C.S. and K.B.), from QBM (to V.S.), from the Ministère de l’Enseignement Supérieur et de la Recherche and from the Fondation ARC pour la Recherche sur le Cancer (to Q.D.), and from EMBO, Marie Curie, and the Daimler und Benz Stiftung (to E.K.)., ANR-11-BSV6-0011,NGD-NSD,Rôle du NSD/NGD: identification des gènes cibles et des facteurs impliqués dans ces mécanismes chez Saccharomyces cerevisiae(2011), ANR-14-CE10-0014,CLEANMD,Mécanismes moléculaires et impact de la voie de dégradation des ARNm nonsense (NMD) sur le transcriptome eucaryote.(2014), Technical University of Munich (TUM)-Ludwig Maximilian University of Munich [Germany] (LMU München)-Helmholtz-Zentrum München (HZM), Max-Planck-Institut für Biochemie (MPIB), Génétique des Interactions macromoléculaires, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz-Zentrum München (HZM)-Ludwig Maximilian University of Munich [Germany] (LMU München)
Subjects: 0301 basic medicine, Saccharomyces cerevisiae Proteins, Protein Conformation, RNA Stability, [SDV]Life Sciences [q-bio], MESH: DNA Helicases, Saccharomyces cerevisiae, Ribosome, 03 medical and health sciences, MESH: Saccharomyces cerevisiae Proteins, MESH: Protein Conformation, RNA, Messenger, Ski complex, MESH: RNA, Messenger, Messenger RNA, Multidisciplinary, biology, Exosome Multienzyme Ribonuclease Complex, MESH: RNA, Fungal, Cryoelectron Microscopy, DNA Helicases, Helicase, Nuclear Proteins, RNA, Fungal, MESH: RNA Stability, Ribosomal RNA, Ribosome Subunits, Large, Eukaryotic, Molecular biology, RNA Helicase A, MESH: Saccharomyces cerevisiae, Cell biology, 030104 developmental biology, MESH: Exosome Multienzyme Ribonuclease Complex, MESH: Ribosome Subunits, Large, Eukaryotic, RNA, Ribosomal, TRAMP complex, biology.protein, MESH: RNA, Ribosomal, MESH: Cryoelectron Microscopy, Eukaryotic Ribosome, MESH: Nuclear Proteins
Abstract: Getting rid of faulty mRNA The cell monitors the health of its mRNAs, destroying those that are faulty or damaged. Destruction by the exosome complex prevents them from being used to synthesize deranged and potentially dangerous proteins. Schmidt et al. determined the structure of the Ski helicase complex, which guides RNAs to the exosome complex destruction machinery in association with a mRNAbound ribosome. The end of the mRNA is threaded from the ribosome into the heart of the helicase, whence the message would be channeled into the maw of the exosome complex. Science , this issue p. 1431
Published: 2016

34. A skill- and feature-based approach to planning process monitoring in assembly planning

Author: Clemens Gonnermann, S. Ehsan Hashemi-Petroodi, Simon Thevenin, Alexandre Dolgui, Rüdiger Daub, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Modélisation, Optimisation et DEcision pour la Logistique, l'Industrie et les Services (LS2N - équipe MODELIS), Laboratoire des Sciences du Numérique de Nantes (LS2N), Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-École Centrale de Nantes (Nantes Univ - ECN), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Institut National de Recherche en Informatique et en Automatique (Inria)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Nantes Université (Nantes Univ), Département Automatique, Productique et Informatique (IMT Atlantique - DAPI), IMT Atlantique (IMT Atlantique), and Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)
Subjects: assembly, [SPI.OTHER]Engineering Sciences [physics]/Other, skill-based approach, Mechanical Engineering, reconfigurable manufacturing system, Industrial and Manufacturing Engineering, [INFO.INFO-AI]Computer Science [cs]/Artificial Intelligence [cs.AI], Computer Science Applications, feature recognition, Control and Systems Engineering, CAD analysis, optimization, Decision support system, Software
Abstract: Frequent changes in customer needs and large product variety are forcing manufacturing companies to move from mass production to mass customization. Customized production can be achieved by introducing reconfigurable production systems (RMS). The customized flexibility and several characteristics of RMSs provide many opportunities in terms of process and production planning. However, those characteristics greatly increase the complexity of the design and planning of production systems. This paper presents a decision support system relying on a skill-based approach to design a reconfigurable assembly line considering the planning of assembly processes and monitoring. The proposed decision aid system is modular in design and is composed of four modules. The main input data is a CAD model of a new product variant for the identification of the assembly and monitoring requirements. Besides, a current assembly system layout with its resource descriptions exists. In the first developed module, assembly-by-disassembly and a skill-based approach are used to generate different assembly plans. In the second module, feature recognition and skill-based approaches generate process monitoring alternatives. The third module uses a linear program (LP) that aims to minimize the total cost of workstation activation and reconfiguration, as well as cycle time, and to maximize the process quality of the assembly tasks. A user-based generative model design approach is applied to optimize the values of three objective functions. In the fourth and final module, a simulation of the optimized assembly plan allows either the validation of the assembly plan and process monitoring plan or initiates a new iteration due to their infeasibility. To further demonstrate how the proposed methodology works, some computational experiments are provided for two use cases.
Published: 2022

35. Moment inequalities for sums of weakly dependent random fields

Author: Blanchard, Gilles, Carpentier, Alexandra, Zadorozhnyi, Oleksandr, Laboratoire de Mathématiques d'Orsay (LMO), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Understanding the Shape of Data (DATASHAPE), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Inria Saclay - Ile de France, Institut National de Recherche en Informatique et en Automatique (Inria), Institut für Mathematik [Potsdam], University of Potsdam = Universität Potsdam, Department of Mathematics [Munich], Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), DFG Forschungsgruppe FOR 5381 'Mathematical Statistics in the Information Age - Statistical Efficiency and Computational Tractability', DFG CRC 1294 - 318763901 'Data Assimilation', Emmy Noether grant MuSyAD (CA 1488/1-1), ANR-19-CHIA-0021,BISCOTTE,Approches statistiquement et computationnellement efficicaces pour l'intelligence artificielle(2019), and ANR-21-CE23-0035,ASCAI,Segmentation, clustering, et seriation actifs et passifs: vers des fondations unifiées en IA(2021)
Subjects: [MATH.MATH-PR]Mathematics [math]/Probability [math.PR], Burkholder-type inequality, [MATH.MATH-ST]Mathematics [math]/Statistics [math.ST], AMS: 60E15, 62M40, 60G60, 60G48, Probability (math.PR), FOS: Mathematics, Mathematics - Statistics Theory, Statistics Theory (math.ST), Concentration inequalities, Weakly dependent random fields, Mathematics - Probability
Abstract: We derive both Azuma-Hoeffding and Burkholder-type inequalities for partial sums over a rectangular grid of dimension $d$ of a random field satisfying a weak dependency assumption of projective type: the difference between the expectation of an element of the random field and its conditional expectation given the rest of the field at a distance more than $\delta$ is bounded, in $L^p$ distance, by a known decreasing function of $\delta$. The analysis is based on the combination of a multi-scale approximation of random sums by martingale difference sequences, and of a careful decomposition of the domain. The obtained results extend previously known bounds under comparable hypotheses, and do not use the assumption of commuting filtrations., Comment: 20 pages, 3 figures
Published: 2023

36. Entry-exit functions in fast-slow systems with intersecting eigenvalues

Author: Kaklamanos, Panagiotis, Kuehn, Christian, Popović, Nikola, Sensi, Mattia, Maxwell Institute for Mathematical Sciences, School of Mathematics - University of Edinburgh, University of Edinburgh, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Mathématiques pour les Neurosciences (MATHNEURO), Inria Sophia Antipolis - Méditerranée (CRISAM), and Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)
Subjects: FOS: Mathematics, Dynamical Systems (math.DS), Mathematics - Dynamical Systems, [MATH]Mathematics [math]
Abstract: We study delayed loss of stability in a class of fast-slow systems with two fast variables and one slow one, where the linearisation of the fast vector field along a one-dimensional critical manifold has two real eigenvalues which intersect before the accumulated contraction and expansion are balanced along any individual eigendirection. That interplay between eigenvalues and eigendirections renders the use of known entry-exit relations unsuitable for calculating the point at which trajectories exit neighbourhoods of the given manifold. We illustrate the various qualitative scenarios that are possible in the class of systems considered here, and we propose novel formulae for the entry-exit functions that underlie the phenomenon of delayed loss of stability therein.
Published: 2023

37. Biallelic Variants in UBA5 Reveal that Disruption of the UFM1 Cascade Can Result in Early-Onset Encephalopathy

Author: Estelle Colin, Jens Daniel, Alban Ziegler, Jamal Wakim, Aurora Scrivo, Tobias B. Haack, Salim Khiati, Anne-Sophie Denommé, Patrizia Amati-Bonneau, Majida Charif, Vincent Procaccio, Pascal Reynier, Kyrieckos A. Aleck, Lorenzo D. Botto, Claudia Lena Herper, Charlotte Sophia Kaiser, Rima Nabbout, Sylvie N’Guyen, José Antonio Mora-Lorca, Birgit Assmann, Stine Christ, Thomas Meitinger, Tim M. Strom, Holger Prokisch, Antonio Miranda-Vizuete, Georg F. Hoffmann, Guy Lenaers, Pascale Bomont, Eva Liebau, Dominique Bonneau, Emmanuelle Génin, Dominique Campion, Jean-François Dartigues, Jean-François Deleuze, Jean-Charles Lambert, Richard Redon, Thomas Ludwig, Benjamin Grenier-Boley, Sébastien Letort, Pierre Lindenbaum, Vincent Meyer, Olivier Quenez, Christian Dina, Céline Bellenguez, Camille Charbonnier -Le Clézio, Joanna Giemza, Stéphanie Chatel, Claude Férec, Hervé Le Marec, Luc Letenneur, Gaël Nicolas, Karen Rouault, Delphine Bacq, Anne Boland, Doris Lechner, Service de génétique [Angers], Université d'Angers (UA)-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), MitoVasc - 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), Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Institut des Neurosciences de Montpellier (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Epilepsies de l'Enfant et Plasticité Cérébrale (U1129), 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), Clinique Médicale Pédiatrique, Centre hospitalier universitaire de Nantes (CHU Nantes), Institute of Human Genetics, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz Zentrum München = German Research Center for Environmental Health, Mitochondrie : Régulations et Pathologie, Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-German Research Center for Environmental Health-Helmholtz-Zentrum München (HZM), Inst MitoVasc, Equipe MitoLab, Université d'Angers (UA), and Technische Universität München [München] (TUM)-Helmholtz-Zentrum München (HZM)-German Research Center for Environmental Health
Subjects: 0301 basic medicine, Male, Microcephaly, Movement disorders, [SDV]Life Sciences [q-bio], Ubiquitin-Activating Enzymes, Endoplasmic Reticulum, Synaptic Transmission, Exome, Genetics(clinical), Age of Onset, Child, Zebrafish, Genetics (clinical), Caenorhabditis elegans, Genetics, Brain Diseases, Brain Mapping, Movement Disorders, biology, Magnetic Resonance Imaging, Cholinergic Neurons, 3. Good health, Child, Preschool, Female, medicine.symptom, Encephalopathy, Genes, Recessive, 03 medical and health sciences, Intellectual Disability, Report, medicine, Gene silencing, Animals, Humans, Caenorhabditis elegans Proteins, Gene, Ubiquitins, Alleles, Epilepsy, Ubiquitin, Endoplasmic reticulum, Proteins, Fibroblasts, Zebrafish Proteins, biology.organism_classification, medicine.disease, 030104 developmental biology, Mutation
Abstract: International audience; Via whole-exome sequencing, we identified rare autosomal-recessive variants in UBA5 in five children from four unrelated families affected with a similar pattern of severe intellectual deficiency, microcephaly, movement disorders, and/or early-onset intractable epilepsy. UBA5 encodes the E1-activating enzyme of ubiquitin-fold modifier 1 (UFM1), a recently identified ubiquitin-like protein. Biochemical studies of mutant UBA5 proteins and studies in fibroblasts from affected individuals revealed that UBA5 mutations impair the process of ufmylation, resulting in an abnormal endoplasmic reticulum structure. In Caenorhabditis elegans, knockout of uba-5 and of human orthologous genes in the UFM1 cascade alter cholinergic, but not glutamatergic, neurotransmission. In addition, uba5 silencing in zebrafish decreased motility while inducing abnormal movements suggestive of seizures. These clinical, biochemical, and experimental findings support our finding of UBA5 mutations as a pathophysiological cause for early-onset encephalopathies due to abnormal protein ufmylation.
Published: 2016

38. SAXO, the SPHERE extreme AO system: on-sky final performance and future improvements

Author: Fusco, T., Sauvage, J.-F., Mouillet, D., Costille, A., Petit, C., Beuzit, J.-L., Dohlen, K., Milli, J., Girard, J., Kasper, M., Vigan, Arthur, Suarez, M., Soenke, C., Downing, M., N'Diaye, M., Baudoz, P., Sevin, A., Baruffolo, A., Schmid, H.-M., Salasnich, B., Hugot, E., Hubin, N., Marchetti, Enrico, Close, Laird, Véran, Jean-Pierre, Schmid, M., Laboratoire d'Astrophysique de Marseille (LAM), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Aix Marseille Université (AMU)-Centre National d'Études Spatiales [Toulouse] (CNES), Laboratoire d'Astrophysique de Grenoble (LAOG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), European Southern Observatory (ESO), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Franche-Comté (UFC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Technologie de Belfort-Montbeliard (UTBM), ESO, Physics Department [Garching], Technical University of Munich (TUM)-Technical University of Munich (TUM), Space Telescope Science Institute (STSci), Laboratoire d'études spatiales et d'instrumentation en astrophysique (LESIA (UMR_8109)), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, PSL Research University (PSL)-PSL Research University (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Anthropologie Moléculaire et Imagerie de Synthèse (AMIS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), INAF - Osservatorio Astronomico di Padova (OAPD), Istituto Nazionale di Astrofisica (INAF), NRC Herzberg Institute of Astrophysics, National Research Council of Canada (NRC), ITA, USA, FRA, DEU, CHE, Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS), Institut de Planétologie et d'Astrophysique de Grenoble (IPAG), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Observatoire des Sciences de l'Univers de Grenoble (OSUG ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national des sciences de l'Univers (INSU - CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées
Subjects: High Contrast Imaging, media_common.quotation_subject, Polarimetry, 01 natural sciences, 7. Clean energy, law.invention, 010309 optics, Telescope, Optics, law, 0103 physical sciences, Adaptive optics, 010303 astronomy & astrophysics, Coronagraph, Instrumentation: Adaptive Optics, media_common, Wavefront, Scientific instrument, Physics, business.industry, Astrophysics::Instrumentation and Methods for Astrophysics, Astronomy, Exoplanet, 13. Climate action, Sky, Astrophysics::Earth and Planetary Astrophysics, business, [PHYS.ASTR]Physics [physics]/Astrophysics [astro-ph]
Abstract: International audience; The SPHERE (Spectro-Polarimetric High-contrast Exoplanet Research) instrument aims at detecting extremely faint sources (giant extrasolar planets) in the vicinity of bright stars1. Such a challenging goal requires the use of a very-high-order performance Adaptive Optics [AO] system feeding the scientific instruments with a quasi-perfect flat wave front corrected from all the atmospheric turbulence and internal defects. This AO system, called SAXO (Sphere Ao for eXoplanet Observation) is the heart of the instrument, a heart beating 1200 time per second and providing unprecedented image quality for a large ground based telescope at optical/near infrared wavelength. We will present the latest results obtained on-sky, demonstrating its exceptional performance (in terms of correction quality, stability and robustness) and tremendous potentiality for high contrast imaging and more specifically for exoplanet discovery.
Published: 2016

39. First light of the VLT planet finder SPHERE. III. New spectrophotometry and astrometry of the HR 8799 exoplanetary system

Author: Zurlo, A., Vigan, Arthur, Galicher, R., Maire, A.L., Mesa, D., Gratton, R., Chauvin, G., Kasper, M., Moutou, C., Bonnefoy, M., Desidera, S., Abe, L., Apai, D., Baruffolo, A., Baudoz, P., Baudrand, J., Beuzit, J.L., Blancard, P., Boccaletti, A., Cantalloube, F., Carle, M., Cascone, E., Charton, P., Claudi, R.U., Costille, A., De Caprio, V., Dohlen, K., Dominik, C., Fantinel, D., Feautrier, P., Feldt, M., Fusco, T., Gigan, P., Girard, J.H., Gisler, D., Gluck, L., Gry, C., Henning, T., Hugot, E., Janson, M., Jaquet, M., Lagrange, A.M., Langlois, M., Llored, M., Madec, F., Magnard, Y., Martinez, P., Maurel, D., Mawet, D., Meyer, M.R., Milli, J., Moeller-Nilsson, O., Mouillet, D., Origné, A., Pavlov, A., Petit, C., Puget, P., Quanz, S.P., Rabou, P., Ramos, J., Rousset, G., Roux, A., Salasnich, B., Salter, G., Sauvage, J.F., Schmid, H.M., Soenke, C., Stadler, E., Suarez, M., Turatto, M., Udry, S., F., Vakili, Wahhaj, Z., Wildi, F., Antichi, J., Universidad Diego Portales [Santiago] (UDP), Departamento de Astronomía, Universidad de Chile = University of Chile [Santiago] (UCHILE), Laboratoire d'Astrophysique de Marseille (LAM), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Aix Marseille Université (AMU)-Centre National d'Études Spatiales [Toulouse] (CNES), INAF - Osservatorio Astronomico di Padova (OAPD), Istituto Nazionale di Astrofisica (INAF), European Southern Observatory, European Southern Observatory (ESO), Laboratoire d'études spatiales et d'instrumentation en astrophysique (LESIA), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut de Planétologie et d'Astrophysique de Grenoble (IPAG), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Observatoire des Sciences de l'Univers de Grenoble (OSUG ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national des sciences de l'Univers (INSU - CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), ESO, Physics Department [Garching], Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Joseph Louis LAGRANGE (LAGRANGE), Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Observatoire de la Côte d'Azur, Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Steward Observatory (STEWARD OBSERVATORY), University of Arizona, Lunar and Planetary Laboratory [Tucson] (LPL), ONERA - The French Aerospace Lab [Châtillon], ONERA-Université Paris Saclay (COmUE), Anton Pannekoek Institute for Astronomy, University of Amsterdam [Amsterdam] (UvA), Max-Planck-Institut für Astronomie (MPIA), Max-Planck-Gesellschaft, Kiepenheuer-Institut für Sonnenphysik (KIS), AlbaNova University Center (ALBANOVA), Stockholm University, Centre de Recherche Astrophysique de Lyon (CRAL), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS), California Institute of Technology (CALTECH), Institute of Astronomy [ETH Zürich], Department of Physics [ETH Zürich] (D-PHYS), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich)- Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Observatoire Astronomique de l'Université de Genève (ObsGE), Université de Genève (UNIGE), Universidad de Chile, Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS), PSL Research University (PSL)-PSL Research University (PSL)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National d'Études Spatiales [Toulouse] (CNES)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire des Sciences de l'Univers de Grenoble (OSUG), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Technical University of Munich (TUM)-Technical University of Munich (TUM), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Observatoire de la Côte d'Azur, Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), ONERA, Université de Lyon-Université de Lyon-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich)-Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), 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 des sciences de l'Univers (INSU - CNRS)-Observatoire de la Côte d'Azur, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Genève = University of Geneva (UNIGE)
Subjects: TRAITEMENT IMAGE, [SPI.OPTI]Engineering Sciences [physics]/Optics / Photonic, SPECTROSCOPIE, ANALYSE DONNEES, ASTROMETRIE, Astrophysics::Earth and Planetary Astrophysics, Astrophysics::Galaxy Astrophysics, HAUTE RESOLUTION, EXOPLANETE
Abstract: International audience; Context. The planetary system discovered around the young A-type HR 8799 provides a unique laboratory to: a) test planet formation theories; b) probe the diversity of system architectures at these separations, and c) perform comparative (exo)planetology.Aims. We present and exploit new near-infrared images and integral-field spectra of the four gas giants surrounding HR 8799 obtained with SPHERE, the new planet finder instrument at the Very Large Telescope, during the commissioning and science verification phase of the instrument (July–December 2014). With these new data, we contribute to completing the spectral energy distribution (SED) of these bodies in the 1.0–2.5 μm range. We also provide new astrometric data, in particular for planet e, to further constrain the orbits.Methods. We used the infrared dual-band imager and spectrograph (IRDIS) subsystem to obtain pupil-stabilized, dual-band H2H3 (1.593 μm, 1.667 μm), K1K2 (2.110 μm, 2.251 μm), and broadband J (1.245 μm) images of the four planets. IRDIS was operated in parallel with the integral field spectrograph (IFS) of SPHERE to collect low-resolution (R ~ 30), near-infrared (0.94–1.64 μm) spectra of the two innermost planets HR 8799 d and e. The data were reduced with dedicated algorithms, such as the Karhunen-Loève image projection (KLIP), to reveal the planets. We used the so-called negative planets injection technique to extract their photometry, spectra, and measure their positions. We illustrate the astrometric performance of SPHERE through sample orbital fits compatible with SPHERE and literature data.Results. We demonstrated the ability of SPHERE to detect and characterize planets in this kind of systems, providing spectra and photometry of its components. The spectra improve upon the signal-to-noise ratio of previously obtained data and increase the spectral coverage down to the Y band. In addition, we provide the first detection of planet e in the J band. Astrometric positions for planets HR 8799 bcde are reported for the epochs of July, August, and December 2014. We measured the photometric values in J, H2H3, K1K2 bands for the four planets with a mean accuracy of 0.13 mag. We found upper limit constraints on the mass of a possible planet f of 3–7 MJup . Our new measurements are more consistent with the two inner planets d and e being in a 2d:1e or 3d:2e resonance. The spectra of HR 8799 d and e are well matched by those of L6-8 field dwarfs. However, the SEDs of these objects are redder than field L dwarfs longward of 1.6 μm.
Published: 2016

40. First light of the VLT planet finder SPHERE. II. The physical properties and the architecture of the young systems PZ Telescopii and HD 1160 revisited

Author: Th. Henning, Emmanuel Hugot, Cyril Petit, Julien Milli, Massimo Turatto, Dimitri Mawet, Silvano Desidera, M. Kasper, O. Möller-Nilsson, Stéphane Udry, Alice Zurlo, A. Pavlov, Enrico Giro, Cecile Gry, M. Millward, Andrea Baruffolo, David Ehrenreich, Sergio Messina, Enrico Cascone, Jean-Luc Beuzit, M. Llored, T. Kopytova, Zahed Wahhaj, Andreas Bazzon, P. Martinez, Norbert Hubin, C. Moutou, Mickael Bonnefoy, Thibaut Moulin, Raffaele Gratton, Kjetil Dohlen, P. Blanchard, L. Weber, S. Rochat, Ch. Ginski, Riccardo Claudi, Pascal Puget, Anne Costille, Alain Origne, M. Carle, D. Le Mignant, Gael Chauvin, David Mouillet, H. M. Schmid, A. Delboulbe, M. Feldt, Anthony Boccaletti, Raphaël Galicher, Arthur Vigan, J. Pragt, D. Gisler, C. Thalmann, Jacopo Antichi, L. Gluck, Jose Ramos, J. de Boer, Anne-Marie Lagrange, Anne-Lise Maire, Ronald Roelfsema, Thierry Fusco, Julien Girard, Farrokh Vakili, Dino Mesa, Bernardo Salasnich, Maud Langlois, V. De Caprio, M. Jaquet, Carsten Dominik, Jean-François Sauvage, Francois Wildi, F. Madec, INAF - Osservatorio Astronomico di Padova (OAPD), Istituto Nazionale di Astrofisica (INAF), Institut de Planétologie et d'Astrophysique de Grenoble (IPAG), Centre National d'Études Spatiales [Toulouse] (CNES)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire des Sciences de l'Univers de Grenoble (OSUG), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Leiden Observatory [Leiden], Universiteit Leiden [Leiden], Laboratoire d'Astrophysique de Marseille (LAM), Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS), European Southern Observatory [Santiago] (ESO), European Southern Observatory (ESO), INAF - Osservatorio Astrofisico di Catania (OACT), Laboratoire d'études spatiales et d'instrumentation en astrophysique (LESIA), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Observatoire de Paris, PSL Research University (PSL)-PSL Research University (PSL)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Max-Planck-Institut für Astronomie (MPIA), Max-Planck-Gesellschaft, Institute for Astronomy [Zürich], Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Geneva Observatory, University of Geneva [Switzerland], Universidad Diego Portales [Santiago] (UDP), Departamento de Astronomia (DAS), Universidad de Santiago de Chile [Santiago] (USACH), Laboratoire d'Astrophysique de Grenoble (LAOG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Euratom/UKAEA Fusion Assoc., Culham Science Centre [Abingdon], Astronomical Institute Anton Pannekoek (AI PANNEKOEK), University of Amsterdam [Amsterdam] (UvA), ONERA - The French Aerospace Lab [Châtillon], ONERA, Centre de Physique des Particules de Marseille (CPPM), Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Aix Marseille Université (AMU), ESO, Physics Department [Garching], Technical University of Munich (TUM)-Technical University of Munich (TUM), Centre de Recherche Astrophysique de Lyon (CRAL), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), UMR 5805 Environnements et Paléoenvironnements Océaniques et Continentaux (EPOC), Observatoire aquitain des sciences de l'univers (OASU), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE)-Centre National de la Recherche Scientifique (CNRS), Caltech Department of Astronomy [Pasadena], California Institute of Technology (CALTECH), Canada-France-Hawaii Telescope Corporation, NASA Goddard Space Flight Center (GSFC), De la Molécule aux Nanos-objets : Réactivité, Interactions et Spectroscopies (MONARIS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Observatoire Astronomique de l'Université de Genève (ObsGE), Université de Genève (UNIGE), Joseph Louis LAGRANGE (LAGRANGE), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Observatoire de la Côte d'Azur, Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), European Synchrotron Radiation Facility (ESRF), Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Observatoire des Sciences de l'Univers de Grenoble (OSUG ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national des sciences de l'Univers (INSU - CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Universiteit Leiden, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Université de Genève = University of Geneva (UNIGE), ONERA-Université Paris Saclay (COmUE), Aix Marseille Université (AMU)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Environnements et Paléoenvironnements OCéaniques (EPOC), Université Sciences et Technologies - Bordeaux 1 (UB)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1 (UB)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Canada-France-Hawaii Telescope Corporation (CFHT), National Research Council of Canada (NRC)-Centre National de la Recherche Scientifique (CNRS)-University of Hawai'i [Honolulu] (UH), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), 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 des sciences de l'Univers (INSU - CNRS)-Observatoire de la Côte d'Azur, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS), Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Sciences et Technologies - Bordeaux 1-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École pratique des hautes études (EPHE), Institut de Chimie du CNRS (INC)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), and Low Energy Astrophysics (API, FNWI)
Subjects: Earth and Planetary Astrophysics (astro-ph.EP), Physics, Very Large Telescope, 010308 nuclear & particles physics, Metallicity, Brown dwarf, FOS: Physical sciences, Astronomy and Astrophysics, Context (language use), Astrophysics, 01 natural sciences, Exoplanet, Luminosity, Photometry (optics), Space and Planetary Science, 0103 physical sciences, Spectral energy distribution, Astrophysics - Instrumentation and Methods for Astrophysics, [PHYS.ASTR]Physics [physics]/Astrophysics [astro-ph], Instrumentation and Methods for Astrophysics (astro-ph.IM), 010303 astronomy & astrophysics, Astrophysics - Earth and Planetary Astrophysics
Abstract: [Abridged] Context. The young systems PZ Tel and HD 1160, hosting known low-mass companions, were observed during the commissioning of the new planet finder SPHERE with several imaging and spectroscopic modes. Aims. We aim to refine the physical properties and architecture of both systems. Methods. We use SPHERE commissioning data and REM observations, as well as literature and unpublished data from VLT/SINFONI, VLT/NaCo, Gemini/NICI, and Keck/NIRC2. Results. We derive new photometry and confirm the nearly daily photometric variability of PZ Tel A. Using literature data spanning 38 yr, we show that the star also exhibits a long-term variability trend. The 0.63-3.8 mic SED of PZ Tel B allows us to revise its properties: spectral type M7+/-1, Teff=2700+/-100 K, log(g)0.66) of PZ Tel B. For e4 MJ) outside 0.5" for the PZ Tel system. We also show that K1-K2 color can be used with YJH low-resolution spectra to identify young L-type companions, provided high photometric accuracy (, 25 pages, 23 figures, accepted for publication in A&A on Oct. 13th, 2015; version including language editing. Typo on co-author name on astroph page corrected, manuscript unchanged
Published: 2016

41. MT5-MMP is a new pro-amyloidogenic proteinase that promotes amyloid ă pathology and cognitive decline in a transgenic mouse model of Alzheimer's disease

Author: Baranger, Kévin, Marchalant, Yannick, Bonnet, Amandine E., Crouzin, Nadine, Carrete, Alex, Paumier, Jean-Michel, Py, Nathalie A., Bernard, Anne, Bauer, Charlotte, Charrat, Eliane, Moschke, Katrin, Seiki, Mothoharu, Vignes, Michel, Lichtenthaler, Stefan F., Checler, Frédéric, Khrestchatisky, Michel, Rivera, Santiago, Neurobiologie des interactions cellulaires et neurophysiopathologie - NICN (NICN), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Psychology/Neuroscience program, Central Michigan University (CMU), Institut de pharmacologie moléculaire et cellulaire (IPMC), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Institute for Advanced Study [Munich] (TUM-IAS), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Klinikums rechts der Isar, The University of Tokyo (UTokyo), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Munich Cluster for systems neurology [Munich] (SyNergy), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU), ANR-08-MNPS-0042,TIMPAD,Interactions fonctionnelles entre le système TIMP/MMP et le LRP-1 dans la maladie d'Alzheimer : identification de nouvelles cibles thérapeutiques(2008), ANR-11-MALZ-0007,PREVENTAD,MMP-12 comme marqueur précoce et cible thérapeutique dans la progression de la maladie d'Alzheimer(2011), ANR-11-EMMA-0014,ADHOC,Utilisation d'un bras haptique pour la programmation des robots et machines d'usinage multi-axes.(2011), ANR-11-LABX-0009,DISTALZ,Développement de stratégies innovantes pour une approche transdisciplinaire de la maladie d'Alzheime(2011), European Project: 256477,PEOPLE,FP7-PEOPLE-2009-RG,NGINFAD(2010), European Project: 224847,PEOPLE,FP7-PEOPLE-2007-4-3-IRG,ADAMNEURON(2008), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Technical University of Munich (TUM), The University of Tokyo, Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Technische Universität München [München] (TUM)-Ludwig-Maximilians-Universität München (LMU), ANR-11-LABX-0009/11-LABX-0009,DISTALZ,Développement de stratégies innovantes pour une approche transdisciplinaire de la maladie d'Alzheime(2011), Khrestchatisky, Michel, Maladies Neurologiques et Psychiatriques - Interactions fonctionnelles entre le système TIMP/MMP et le LRP-1 dans la maladie d'Alzheimer : identification de nouvelles cibles thérapeutiques - - TIMPAD2008 - ANR-08-MNPS-0042 - MNP - VALID, Maladie d'Alzheimer et Maladies Apparentées - MMP-12 comme marqueur précoce et cible thérapeutique dans la progression de la maladie d'Alzheimer - - PREVENTAD2011 - ANR-11-MALZ-0007 - MALZ - VALID, Emergence de produits, technologies, ou services à fort potentiel de valorisation - Utilisation d'un bras haptique pour la programmation des robots et machines d'usinage multi-axes. - - ADHOC2011 - ANR-11-EMMA-0014 - Emergence - VALID, Laboratoires d'excellence - Développement de stratégies innovantes pour une approche transdisciplinaire de la maladie d'Alzheime - - DISTALZ2011 - ANR-11-LABX-0009 - LABX - VALID, Targeting Inflammation and Neurogenesis using cannabinoids to delay the onset of Alzheimer's disease - NGINFAD - - PEOPLE2010-04-01 - 2014-03-31 - 256477 - VALID, Study and Identification of ADAM10 as Neuronal α-secretase in relation to Alzheimer's disease - ADAMNEURON - - PEOPLE2008-04-01 - 2012-03-31 - 224847 - VALID, Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), and Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)
Subjects: Knockout mouse, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MMP-24, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Neurodegenerative disease, Synaptotoxicity, Neuroprotection
Abstract: International audience; Membrane-type 5-matrix metalloproteinase (MT5-MMP) is a proteinase mainly expressed in the nervous system with emerging roles in brain pathophysiology. The implication of MT5-MMP in Alzheimer’s disease (AD), notably its interplay with the amyloidogenic process, remains elusive. Accordingly, we crossed the genetically engineered 5xFAD mouse model of AD with MT5-MMP-deficient mice and examined the impact of MT5-MMP deficiency in bigenic 5xFAD/MT5-MMP−/− mice. At early stages (4 months) of the pathology, the levels of amyloid beta peptide (Aβ) and its amyloid precursor protein (APP) C-terminal fragment C99 were largely reduced in the cortex and hippocampus of 5xFAD/MT5-MMP−/−, compared to 5xFAD mice. Reduced amyloidosis in bigenic mice was concomitant with decreased glial reactivity and interleukin-1β (IL-1β) levels, and the preservation of long-term potentiation (LTP) and spatial learning, without changes in the activity of α-, β- and γ-secretases. The positive impact of MT5-MMP deficiency was still noticeable at 16 months of age, as illustrated by reduced amyloid burden and gliosis, and a better preservation of the cortical neuronal network and synaptophysin levels in bigenic mice. MT5-MMP expressed in HEKswe cells colocalized and co-immunoprecipitated with APP and significantly increased the levels of Aβ and C99. MT5-MMP also promoted the release of a soluble APP fragment of 95 kDa (sAPP95) in HEKswe cells. sAPP95 levels were significantly reduced in brain homogenates of 5xFAD/MT5-MMP−/− mice, supporting altogether the idea that MT5-MMP influences APP processing. MT5-MMP emerges as a new pro-amyloidogenic regulator of APP metabolism, whose deficiency alleviates amyloid pathology, neuroinflammation and cognitive decline.
Published: 2016

42. Severe respiratory complex III defect prevents liver adaptation to prolonged fasting

Author: Pierre Lesimple, Neji Tebib, Tim M. Strom, Thomas Meitinger, Holger Prokisch, Guy Touati, Anne Lombès, Claude Jardel, Mylène Gilleron, Tobias B. Haack, Caroline L’hermitte-Stead, Hélène Ogier de Baulny, Sandrine Filaut, Laura S. Kremer, Hatem Azzouz, Institute of Human Genetics, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz Zentrum München = German Research Center for Environmental Health, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Biochimie Métabolique et Centre de Génétique moléculaire et chromosomique [CHU Pitié Salpêtrière], 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), Hôpital La Rabta [Tunis], Service de neurologie pédiatrique et maladies métaboliques, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service Gastroentérologie, hépatologie nutrition, diabétologie et maladies héréditaires du métabolisme pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), This work was supported by grants from the FRM (Fondation pour la Recherche Médicale) grant DPM20121125550 to AL, from the Association Française contre les Myopathies (AFM) to AL and Association contre les Maladies Mitochondriales (AMMi) to AL, German Bundesministerium für Bildung und Forschung (BMBF) through funding of the E-Rare project GENOMIT (01GM1207) (TM, HP), German Network for mitochondrial disorders (mitoNET, 01GM1113C) (TM, HP)., Lombès, Anne, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-German Research Center for Environmental Health-Helmholtz-Zentrum München (HZM), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hépatologie et Maladies Héréditaires du Métabolisme, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse]-Centre de référence commun pour les maladies héréditaires du métabolisme, Technische Universität München [München] ( TUM ) -German Research Center for Environmental Health-Helmholtz-Zentrum München ( HZM ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Hôpital La Rabta [Tunis), and Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 )
Subjects: 0301 basic medicine, LYRM7, fasting, hyperammonemia, MTO1, Biology, Bioinformatics, Article, Mitochondrial Proteins, 03 medical and health sciences, symbols.namesake, 0302 clinical medicine, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, respiratory complex III, medicine, Mitochondrial oxidative phosphorylation pathway, Humans, Exome, Genetics, Sanger sequencing, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Hepatology, Respiration, Homozygote, liver failure, High-Throughput Nucleotide Sequencing, Hyperammonemia, medicine.disease, Adaptation, Physiological, 3. Good health, Complementation, 030104 developmental biology, hypoglycemia, Liver, Lactic acidosis, Coenzyme Q – cytochrome c reductase, symbols, functional complementation, Liver function, Severe lactic acidosis, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Next generation sequencing approaches have tremendously improved the diagnosis of rare genetic diseases. It may however be faced with difficult clinical interpretation of variants. Inherited enzymatic diseases provide an invaluable possibility to evaluate the function of the defective enzyme in human cell biology. This is the case for respiratory complex III, which has 11 structural subunits and requires several assembly factors. An important role of complex III in liver function is suggested by its frequent impairment in human cases of genetic complex III defects.We report the case of a child with complex III defect and acute liver dysfunction with lactic acidosis, hypoglycemia, and hyperammonemia. Mitochondrial activities were assessed in liver and fibroblasts using spectrophotometric assays. Genetic analysis was done by exome followed by Sanger sequencing. Functional complementation of defective fibroblasts was performed using lentiviral transduction followed by enzymatic analyses and expression assays.Homozygous, truncating, mutations in LYRM7 and MTO1, two genes encoding essential mitochondrial proteins were found. Functional complementation of the complex III defect in fibroblasts demonstrated the causal role of LYRM7 mutations. Comparison of the patient's clinical history to previously reported patients with complex III defect due to nuclear DNA mutations, some actually followed by us, showed striking similarities allowing us to propose common pathophysiology.Profound complex III defect in liver does not induce actual liver failure but impedes liver adaptation to prolonged fasting leading to severe lactic acidosis, hypoglycemia, and hyperammonemia, potentially leading to irreversible brain damage.The diagnosis of rare genetic disease has been tremendously accelerated by the development of high throughput sequencing technology. In this paper we report the investigations that have led to identify LYRM7 mutations causing severe hepatic defect of respiratory complex III. Based on the comparison of the patient's phenotype with other cases of complex III defect, we propose that profound complex III defect in liver does not induce actual liver failure but impedes liver adaptation to prolonged fasting.
Published: 2016

43. Isogeometric dual mortar methods for computational contact mechanics

Author: Wolfgang A. Wall, Alexander Seitz, Barbara Wohlmuth, Johannes Kremheller, Philipp Farah, Alexander Popp, Institute for Computational Mechanics, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Institute for Numerical Mathematics, Department of Mathematics [Munich], and Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)
Subjects: Mortar finite element methods, Computational Mechanics, General Physics and Astronomy, Unilateral contact, Basis function, 010103 numerical & computational mathematics, Isogeometric analysis, 01 natural sciences, symbols.namesake, [SPI]Engineering Sciences [physics], Ingenieurwissenschaften, Dual Lagrange multipliers, Computational mechanics, Isogeometric analysis, Contact mechanics, Mortar finite element methods, Dual Lagrange multipliers, Finite deformation, 0101 mathematics, Mortar methods, Mathematics, Mechanical Engineering, Mathematical analysis, Lagrange polynomial, Domain decomposition methods, Finite deformation, Computer Science Applications, 010101 applied mathematics, Contact mechanics, Mechanics of Materials, Lagrange multiplier, symbols, ddc:620
Abstract: International audience; In recent years, isogeometric analysis (IGA) has received great attention in many fields of computational mechanics research. Especially for computational contact mechanics, an exact and smooth surface representation is highly desirable. As a consequence, many well-known finite e lement m ethods a nd a lgorithms f or c ontact m echanics h ave b een t ransferred t o I GA. I n t he present contribution, the so-called dual mortar method is investigated for both contact mechanics and classical domain decomposition using NURBS basis functions. In contrast to standard mortar methods, the use of dual basis functions for the Lagrange multiplier based on the mathematical concept of biorthogonality enables an easy elimination of the additional Lagrange multiplier degrees of freedom from the global system. This condensed system is smaller in size, and no longer of saddle point type but positive definite. A very simple and commonly used element-wise construction of the dual basis functions is directly transferred to the IGA case. The resulting Lagrange multiplier interpolation satisfies discrete inf–sup stability and biorthogonality, however, the reproduction order is limited to one. In the domain decomposition case, this results in a limitation of the spatial convergence order to O(h 3 /2) in the energy norm, whereas for unilateral contact, due to the lower regularity of the solution, optimal convergence rates are still met. Numerical examples are presented that illustrate these theoretical considerations on convergence rates and compare the newly developed isogeometric dual mortar contact formulation with its standard mortar counterpart as well as classical finite elements based on first and second order Lagrange polynomials.
Published: 2016

44. The SPHERE view of the planet-forming disk around HD 100546

Author: Thomas Henning, Francois Menard, Andreas Bazzon, Antonio Garufi, Henning Avenhaus, E. Sissa, Markus Kasper, Anthony K. Cheetham, Gijs D. Mulders, Markus Janson, Raffaele Gratton, Jean-Charles Augereau, Francois Wildi, Graeme Salter, Anne-Lise Maire, Dino Mesa, Anne-Marie Lagrange, Tomas Stolker, Esther Buenzli, Carsten Dominik, Wolfgang Brandner, Markus Feldt, Myriam Benisty, Silvano Desidera, Maud Langlois, Clément Perrot, Gael Chauvin, David Mouillet, Bruno Lopez, Sascha P. Quanz, Anthony Boccaletti, Christian Ginski, Arthur Vigan, Mickael Bonnefoy, Raphael Galicher, Christophe Pinte, J. Lannier, Alice Zurlo, S. Peretti, Michael Meyer, Hans Martin Schmid, M. Cudel, Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Laboratoire d'études spatiales et d'instrumentation en astrophysique (LESIA), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre de Recherche Astrophysique de Lyon (CRAL), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS), Institut de Planétologie et d'Astrophysique de Grenoble (IPAG), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Observatoire des Sciences de l'Univers de Grenoble (OSUG ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national des sciences de l'Univers (INSU - CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Joseph Louis LAGRANGE (LAGRANGE), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de la Côte d'Azur, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Astronomical Institute Anton Pannekoek (AI PANNEKOEK), University of Amsterdam [Amsterdam] (UvA), Max-Planck-Institut für Astronomie (MPIA), Max-Planck-Gesellschaft, GDFSuez, Laboratoire Franco-Chilien d'Astronomie (LFCA), Universidad de Concepción [Chile]-Pontificia Universidad Católica de Chile (UC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Universidad de Chile, Laboratoire d'Astrophysique de Marseille (LAM), Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS), ESO, Physics Department [Garching], Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), aucun, IDELE, University of Geneva, Genève, Low Energy Astrophysics (API, FNWI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Aix Marseille Université (AMU)-Centre National d'Études Spatiales [Toulouse] (CNES), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), PSL Research University (PSL)-PSL Research University (PSL)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Université de Lyon-Université de Lyon-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National d'Études Spatiales [Toulouse] (CNES)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire des Sciences de l'Univers de Grenoble (OSUG), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Observatoire de la Côte d'Azur, Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Technical University of Munich (TUM)-Technical University of Munich (TUM), Laboratoire d'Astrophysique de Grenoble (LAOG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Universidad de Chile = University of Chile [Santiago] (UCHILE)-Pontificia Universidad Católica de Chile (UC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Universidad de Concepción - University of Concepcion [Chile], and Institut de l'élevage (IDELE)
Subjects: Physics, Earth and Planetary Astrophysics (astro-ph.EP), Brightness, Photon, 010504 meteorology & atmospheric sciences, Be star, Scattering, Conjunction (astronomy), FOS: Physical sciences, Astronomy and Astrophysics, Astrophysics, 01 natural sciences, Astrophysics - Solar and Stellar Astrophysics, Space and Planetary Science, Planet, 0103 physical sciences, Astrophysics::Earth and Planetary Astrophysics, Adaptive optics, [PHYS.ASTR]Physics [physics]/Astrophysics [astro-ph], 010303 astronomy & astrophysics, Image resolution, Solar and Stellar Astrophysics (astro-ph.SR), Astrophysics::Galaxy Astrophysics, 0105 earth and related environmental sciences, Astrophysics - Earth and Planetary Astrophysics
Abstract: We image with unprecedented spatial resolution and sensitivity disk features that could be potential signs of planet-disk interaction. Two companion candidates have been claimed in the disk around the young Herbig Ae/Be star HD100546. Thus, this object serves as an excellent target for our investigation of the natal environment of giant planets. We exploit the power of extreme adaptive optics operating in conjunction with the new high-contrast imager SPHERE to image HD100546 in scattered light. We obtain the first polarized light observations of this source in the visible (with resolution as fine as 2 AU) and new H and K band total intensity images that we analyze with the Pynpoint package. The disk shows a complex azimuthal morphology, where multiple scattering of photons most likely plays an important role. High brightness contrasts and arm-like structures are ubiquitous in the disk. A double-wing structure (partly due to ADI processing) resembles a morphology newly observed in inclined disks. Given the cavity size in the visible (11 AU), the CO emission associated to the planet candidate 'c' might arise from within the circumstellar disk. We find an extended emission in the K band at the expected location of 'b'. The surrounding large-scale region is the brightest in scattered light. There is no sign of any disk gap associated to 'b'., Accepted by A&A. 13 pages, 5 figures
Published: 2016

45. Variationally consistent discretization schemes and numerical algorithms for contact problems

Author: Barbara Wohlmuth, Institute for Numerical Mathematics, Department of Mathematics [Munich], and Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)
Subjects: Numerical Analysis, Mathematical optimization, Discretization, Computer science, General Mathematics, 010103 numerical & computational mathematics, Solver, System of linear equations, 01 natural sciences, ddc, 010101 applied mathematics, [SPI]Engineering Sciences [physics], symbols.namesake, Lagrange multiplier, Variational inequality, Neumann boundary condition, symbols, Differentiable function, [MATH]Mathematics [math], 0101 mathematics, Saddle
Abstract: We consider variationally consistent discretization schemes for mechanical contact problems. Most of the results can also be applied to other variational inequalities, such as those for phase transition problems in porous media, for plasticity or for option pricing applications from finance. The starting point is to weakly incorporate the constraint into the setting and to reformulate the inequality in the displacement in terms of a saddle-point problem. Here, the Lagrange multiplier represents the surface forces, and the constraints are restricted to the boundary of the simulation domain. Having a uniform inf-sup bound, one can then establish optimal low-ordera prioriconvergence rates for the discretization error in the primal and dual variables. In addition to the abstract framework of linear saddle-point theory, complementarity terms have to be taken into account. The resulting inequality system is solved by rewriting it equivalently by means of the non-linear complementarity function as a system of equations. Although it is not differentiable in the classical sense, semi-smooth Newton methods, yielding super-linear convergence rates, can be applied and easily implemented in terms of a primal–dual active set strategy. Quite often the solution of contact problems has a low regularity, and the efficiency of the approach can be improved by using adaptive refinement techniques. Different standard types, such as residual- and equilibrated-baseda posteriorierror estimators, can be designed based on the interpretation of the dual variable as Neumann boundary condition. For the fully dynamic setting it is of interest to apply energy-preserving time-integration schemes. However, the differential algebraic character of the system can result in high oscillations if standard methods are applied. A possible remedy is to modify the fully discretized system by a local redistribution of the mass. Numerical results in two and three dimensions illustrate the wide range of possible applications and show the performance of the space discretization scheme, non-linear solver, adaptive refinement process and time integration.
Published: 2011

46. Simulation of winter wheat response to variable sowing dates and densities in a high-yielding environment

Author: Dueri, Sibylle, Brown, Hamish, Asseng, Senthold, Ewert, Frank, Webber, Heidi, George, Mike, Craigie, Rob, Guarin, Jose Rafael, Pequeno, Diego N.L., Stella, Tommaso, Ahmed, Mukhtar, Alderman, Phillip D., Basso, Bruno, Berger, Andres G., Mujica, Gennady Bracho, Cammarano, Davide, Chen, Yi, Dumont, Benjamin, Rezaei, Ehsan Eyshi, Fereres, Elias, Ferrise, Roberto, Gaiser, Thomas, Gao, Yujing, Garcia-Vila, Margarita, Gayler, Sebastian, Hochman, Zvi, Hoogenboom, Gerrit, Kersebaum, Kurt C., Nendel, Claas, Olesen, Jørgen E., Padovan, Gloria, Palosuo, Taru, Priesack, Eckart, Pullens, Johannes W.M., Rodríguez, Alfredo, Rötter, Reimund P., Ramos, Margarita Ruiz, Semenov, Mikhail A., Senapati, Nimai, Siebert, Stefan, Srivastava, Amit Kumar, Stöckle, Claudio, Supit, Iwan, Tao, Fulu, Thorburn, Peter, Wang, Enli, Weber, Tobias Karl David, Xiao, Liujun, Zhao, Chuang, Zhao, Jin, Zhao, Zhigan, Zhu, Yan, Martre, Pierre, Rebetzke, Greg, Écophysiologie des Plantes sous Stress environnementaux (LEPSE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), The New Zealand Institute for Plant & Food Research Limited [Auckland] (Plant & Food Research), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Leibniz-Zentrum für Agrarlandschaftsforschung = Leibniz Centre for Agricultural Landscape Research (ZALF), Institut für Nutzpflanzenwissenschaften und Ressourcenschutz (INRES), Rheinische Friedrich-Wilhelms-Universität Bonn, Brandenburg University of Technology [Cottbus – Senftenberg] (BTU), Foundation for Arable Research (FAR), University of Florida [Gainesville] (UF), Earth Institute at Columbia University, Columbia University [New York], International Maize and Wheat Improvement Center (CIMMYT), Consultative Group on International Agricultural Research [CGIAR] (CGIAR), Swedish University of Agricultural Sciences (SLU), Pir Mehr Ali Shah Arid Agriculture University = PMAS-Arid Agriculture University Rawalpindi (AAUR), Oklahoma State University [Stillwater] (OSU), Michigan State University [East Lansing], Michigan State University System, Instituto Nacional de Investigación Agropecuaria (INIA), Georg-August-University = Georg-August-Universität Göttingen, Aarhus University [Aarhus], Institute of geographical sciences and natural resources research [CAS] (IGSNRR), Chinese Academy of Sciences [Beijing] (CAS), Gembloux Agro-Bio Tech [Gembloux], Université de Liège, Instituto de Agricultura Sostenible - Institute for Sustainable Agriculture (IAS CSIC), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Universidad de Córdoba = University of Córdoba [Córdoba], Department of Agriculture, Food, Environment and Forestry (DAGRI), Università degli Studi di Firenze = University of Florence (UniFI), Institute of Crop Science and Resource Conservation [Bonn] (INRES), University of Hohenheim, Commonwealth Scientific and Industrial Research Organisation [Canberra] (CSIRO), Global Change Research Centre (CzechGlobe), University of Potsdam = Universität Potsdam, Natural Resources Institute Finland (LUKE), Helmholtz Zentrum München = German Research Center for Environmental Health, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Institute of Biochemical Plant Pathology (BIOP), Centro de Estudios e Investigación para la Gestión de Riesgos Agrarios y Medioambientales (CEIGRAM), Universidad Politécnica de Madrid (UPM), Universidad de Castilla-La Mancha = University of Castilla-La Mancha (UCLM), Centre for Biodiversity and Sustainable Land-use [University of Göttingen] (CBL), Rothamsted Research, Biotechnology and Biological Sciences Research Council (BBSRC), Washington State University (WSU), Wageningen University and Research [Wageningen] (WUR), Zhejiang University, Nanjing Agricultural University (NAU), China Agricultural University (CAU), Agricultural Model Intercomparison and Improvement Project (AgMIP) Wheat Phase 4 and was supported by the French National Research Institute for Agriculture, Food (INRAE) and the International Maize and Wheat Improvement Center (CIMMYT) through the International Wheat Yield Partnership (IWYP, grant IWYP115)., metaprogram Agriculture and forestry in the face of climate change: adaptation and mitigation (CLIMAE) of INRAE, grant-aided support from the Biotechnology and Biological Sciences Research Council (BBSRC) through Designing Future Wheat [BB/P016855/1] and Achieving Sustainable Agricultural Systems [NE/N018125/1] jointly funded with NERC, DivCSA project funded by the Academy of Finland (decision no. 316215)., National Natural Science Foundation of China (No. 31761143006), financial support from BARISTA project (031B0811A) through ERA-NET SusCrop under EU-FACCE JPI, German Federal Ministry of Education and Research (BMBF) through the BonaRes project ’’I4S’’ (031B0513I), German Federal Ministry of Education and Research (BMBF) through the BonaRes Project 'Soil3' (FKZ 031B0026A), Ministry of Education, Youth and Sports of Czech Republic through SustES—Adaption strategies for sustainable ecosystem services and food security under adverse environmental conditions (CZ.02.1.01/0.0/0.0/16_019/000797), Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy – EXC 2070 – 390732324', German Research Foundation (DFG, Grant Agreement SFB 1253/1 2017), European Project: 618105,EC:FP7:KBBE,FP7-ERANET-2013-RTD,FACCE ERA NET PLUS(2013), Institut National de la Recherche Agronomique (France), International Maize and Wheat Improvement Center, International Wheat Yield Partnership, National Natural Science Foundation of China, European Commission, Federal Ministry of Education and Research (Germany), Ministry of Education, Youth and Sports (Czech Republic), German Research Foundation, Biotechnology and Biological Sciences Research Council (UK), Natural Environment Research Council (UK), and Academy of Finland
Subjects: [SDV.SA]Life Sciences [q-bio]/Agricultural sciences, Physiology, Climate Change, sowing date, Plant Science, CHINA, Multi-model Ensemble, New Zealand, Sowing Date, Sowing Density, Tiller Mortality, Tillering, Wheat, Yield Potential, tillering, wheat, USE EFFICIENCY, sowing density, Life Science, Biomass, ADAPTATION, PLANT-DENSITY, Triticum, METAANALYSIS, Multi-model ensemble, WIMEK, CLIMATE-CHANGE, tiller mortality, PRODUCTIVITY, Temperature, CROP MODELS, yield potential, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, ROTATION, GROWTH, Water Systems and Global Change, Seasons
Abstract: Crop multi-model ensembles (MME) have proven to be effective in increasing the accuracy of simulations in modelling experiments. However, the ability of MME to capture crop responses to changes in sowing dates and densities has not yet been investigated. These management interventions are some of the main levers for adapting cropping systems to climate change. Here, we explore the performance of a MME of 29 wheat crop models to predict the effect of changing sowing dates and rates on yield and yield components, on two sites located in a high-yielding environment in New Zealand. The experiment was conducted for 6 years and provided 50 combinations of sowing date, sowing density and growing season. We show that the MME simulates seasonal growth of wheat well under standard sowing conditions, but fails under early sowing and high sowing rates. The comparison between observed and simulated in-season fraction of intercepted photosynthetically active radiation (FIPAR) for early sown wheat shows that the MME does not capture the decrease of crop above ground biomass during winter months due to senescence. Models need to better account for tiller competition for light, nutrients, and water during vegetative growth, and early tiller senescence and tiller mortality, which are exacerbated by early sowing, high sowing densities, and warmer winter temperatures., This study was a part of the Agricultural Model Intercomparison and Improvement Project (AgMIP) Wheat Phase 4 and was supported by the French National Research Institute for Agriculture, Food (INRAE) and the International Maize and Wheat Improvement Center (CIMMYT) through the International Wheat Yield Partnership (IWYP, grant IWYP115). SD and PM acknowledge support from the metaprogram Agriculture and forestry in the face of climate change: adaptation and mitigation (CLIMAE) of INRAE. YC and FT acknowledge support from the National Natural Science Foundation of China (No. 31761143006). RPR and GBM acknowledge financial support from BARISTA project (031B0811A) through ERA-NET SusCrop under EU-FACCE JPI. KCK was funded by the German Federal Ministry of Education and Research (BMBF) through the BonaRes project ’’I4S’’ (031B0513I). AS and TG acknowledge funding by the German Federal Ministry of Education and Research (BMBF) through the BonaRes Project “Soil3” (FKZ 031B0026A). KCK and JEO were supported by the Ministry of Education, Youth and Sports of Czech Republic through SustES—Adaption strategies for sustainable ecosystem services and food security under adverse environmental conditions (CZ.02.1.01/0.0/0.0/16_019/000797). FE acknowledges support by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy – EXC 2070 – 390732324”. TKDW was funded by the German Research Foundation (DFG, Grant Agreement SFB 1253/1 2017). MAS and NS at Rothamsted Research received grant-aided support from the Biotechnology and Biological Sciences Research Council (BBSRC) through Designing Future Wheat [BB/P016855/1] and Achieving Sustainable Agricultural Systems [NE/N018125/1] jointly funded with NERC. TP and FT are supported by the DivCSA project funded by the Academy of Finland (decision no. 316215).
Published: 2022

47. Aim-Aware Collision Monitoring: Discriminating between Expected and Unexpected Post-Impact Behaviors

Author: Proper, Benn, Kurdas, Alexander, Abdolshah, Saeed, Haddadin, Sami, Saccon, Alessandro, Eindhoven University of Technology [Eindhoven] (TU/e), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), European Project: GA 871899,I.AM., and European Project: 871899,I.AM.(2020)
Subjects: [SPI.MECA.GEME]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Mechanical engineering [physics.class-ph]
Abstract: International audience; To speed up and reduce power consumption per cycle in robotic manipulation, one option is to exploit intentional collisions with the surrounding environment and objects, an approach referred to as impact-aware manipulation. Within this context, this paper focuses on developing an online collision monitoring framework for distinguishing between expected and unexpected post-impact behaviors. The classification is based on a desired post-impact motion created via an idealized rigid robot-object-environment model. To generate a classification error bound, it employs a causal envelop filter that is needed due to the unavoidable joint and environment flexibility. In this way, it becomes possible to compare a desired idealized rigid response, which is straightforward to obtain with existing tools, with a measured impact response, which is affected by difficult-to-model post-impact oscillations. The classifier can be used for single-contact as well as multi-contact impact scenarios, such as those occurring in surface-to-surface impacts, and allows for tuning of the sensitivity between expected and unexpected postimpact behaviors. The monitoring framework fuses a (bandpass) momentum observer with impact-aware control to extend the classical collision event pipeline. As a proof of concept, we show the effectiveness of the approach through numerical simulations as well as with preliminary experimental results.
Published: 2023

48. Hepatitis B Virus Targets Lipid Transport Pathways to Infect Hepatocytes

Author: Knud Esser, Xiaoming Cheng, Jochen M. Wettengel, Julie Lucifora, Lea Hansen-Palmus, Katharina Austen, Armando A.R. Suarez, Sarah Heintz, Barbara Testoni, Firat Nebioglu, Minh Tu Pham, Shangqing Yang, Alma Zernecke, Dirk Wohlleber, Marc Ringelhan, Mathias Broxtermann, Daniel Hartmann, Norbert Hüser, Julia Mergner, Andreas Pichlmair, Wolfgang E. Thasler, Mathias Heikenwalder, Georg Gasteiger, Andreas Blutke, Axel Walch, Percy A. Knolle, Ralf Bartenschlager, Ulrike Protzer, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), Universität Heidelberg [Heidelberg] = Heidelberg University, University Hospital of Würzburg, Helmholtz Zentrum München = German Research Center for Environmental Health, German Center for Infection Research, Partnersite Munich (DZIF), Klinikums rechts der Isar, Ludwig-Maximilians University [Munich] (LMU), Technische Universität München = Technical University of Munich (TUM), and Helmholtz Zentrum München (HMGU)
Subjects: lipoprotein metabolism, liver targeting, Hepatology, trans-infection, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Transcytosis
Abstract: International audience; Background and aims: A single hepatitis B virus (HBV) particle is sufficient to establish chronic infection of the liver after intravenous injection, suggesting that the virus targets hepatocytes via a highly efficient transport pathway. We therefore investigated whether HBV utilizes a physiological liver-directed pathway that supports specific host-cell targeting in vivo.Methods: We established an ex vivo system of perfused human liver tissue that recapitulates the liver physiology to investigate HBV liver targeting. This model allowed us to investigate virus-host cell interactions in a cellular microenvironment mimicking the in vivo situation. Results: HBV was rapidly sequestered by liver macrophages within one hour after a virus pulse, but was detected in hepatocytes only after 16 hours. We found that HBV associates with lipoproteins. Electron- and immunofluorescence microscopy corroborated a co-localization in recycling endosomes within peripheral and liver macrophages. Importantly, recycling endosomes accumulated HBV and cholesterol, followed by transport of HBV back to the cell surface along the cholesterol efflux pathway. To reach hepatocytes as final target cells, HBV was able to utilise the hepatocyte-directed cholesterol transport machinery of macrophages.Conclusions: Our results propose that HBV by binding to liver targeted lipoproteins and utilizing the reverse cholesterol transport pathway of macrophages hijacks the physiological lipid transport pathways to the liver to most efficiently reach its target organ. This may involve trans-infection of liver macrophages and result in deposition of HBV in the perisinusoidal space from where HBV can bind its receptor on hepatocytes
Published: 2023

49. The VLT/NaCo large program to probe the occurrence of exoplanets and brown dwarfs at wide orbits. III. The frequency of brown dwarfs and giant planets as companions to solar-type stars

Author: Biller, B., Bonavita, M., Desidera, S., Reggiani, M., Meyer, M., Chauvin, G., Vigan, A., Quanz, S., Delorme, P., Hagelberg, J., Maire, A., Boccaletti, A., Beuzit, J., Buenzli, E., Carson, J., Covino, E., Feldt, M., Girard, J., Gratton, R., Henning, T., Kasper, M., Lagrange, A., Mesa, D., Messina, S., Montagnier, G., Mordasini, C., Mouillet, D., Schlieder, J., Segransan, D., Thalmann, C., Zurlo, A., Vigan, Arthur, Dipartimento di Biochimica G. Moruzzi Sez di Chimica e Propedeutica Biochimica Bologna 40126, GDFSuez, Institut de Planétologie et d'Astrophysique de Grenoble (IPAG), Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Observatoire des Sciences de l'Univers de Grenoble (OSUG ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national des sciences de l'Univers (INSU - CNRS)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire d'Astrophysique de Marseille (LAM), Aix Marseille Université (AMU)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Laboratoire d'études spatiales et d'instrumentation en astrophysique (LESIA), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Max-Planck-Institut für Astronomie (MPIA), Max-Planck-Gesellschaft, ESO, Physics Department [Garching], Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), European Southern Observatory (ESO), Physikalisches Institut [Bern], Universität Bern [Bern], Observatoire Astronomique de l'Université de Genève (ObsGE), Université de Genève (UNIGE), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Universität Bern [Bern] (UNIBE), Université de Genève = University of Geneva (UNIGE), Centre National d'Études Spatiales [Toulouse] (CNES)-Université Grenoble Alpes (UGA)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire des Sciences de l'Univers de Grenoble (OSUG), Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Université Joseph Fourier - Grenoble 1 (UJF)-Centre National de la Recherche Scientifique (CNRS), Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology in Zürich [Zürich] (ETH Zürich), Laboratoire d'Astrophysique de Grenoble (LAOG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), PSL Research University (PSL)-PSL Research University (PSL)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), and Technical University of Munich (TUM)-Technical University of Munich (TUM)
Subjects: 010504 meteorology & atmospheric sciences, Brown dwarf, FOS: Physical sciences, Astrophysics, 01 natural sciences, Planet, 0103 physical sciences, Astrophysics::Solar and Stellar Astrophysics, 010303 astronomy & astrophysics, Solar and Stellar Astrophysics (astro-ph.SR), Astrophysics::Galaxy Astrophysics, 0105 earth and related environmental sciences, Physics, Earth and Planetary Astrophysics (astro-ph.EP), Mass distribution, Astronomy and Astrophysics, Planetary system, Exoplanet, Radial velocity, Stars, Astrophysics - Solar and Stellar Astrophysics, Space and Planetary Science, Mass spectrum, Astrophysics::Earth and Planetary Astrophysics, [PHYS.ASTR]Physics [physics]/Astrophysics [astro-ph], Astrophysics - Earth and Planetary Astrophysics
Abstract: In recent years there have been many attempts to characterize the occurrence of stellar, BD and planetary-mass companions to solar-type stars, with the aim of constraining formation mechanisms. From RV observations a dearth of companions with masses between 10-40 MJup has been noticed at close separations, suggesting the possibility of a distinct formation mechanism for objects above and below this range. We present a model for the substellar companion mass function (CMF). It consists of the superposition of the planet and BD companion mass distributions, assuming that we can extrapolate the RV measured companion mass function for planets to larger separations and the stellar companion mass-ratio distribution over all separations into the BD mass regime. By using both the results of the VLT/NaCo large program and the complementary archive datasets that probe the occurrence of planets and BDs on wide orbits around solar-type stars, we place some constraints on the planet and BD distributions. We developed a MC simulation tool to predict the outcome of a given survey, depending on the shape of the orbital parameter distributions. Comparing the predictions with the results of the observations, we calculate how likely different models are and which can be ruled out. Current observations are consistent with the proposed model for the CMF, as long as a sufficiently small outer truncation radius is introduced for the planet separation distribution. The results of the direct imaging surveys searching for substellar companions around Sun-like stars are consistent with a combined substellar mass spectrum of planets and BDs. This mass distribution has a minimum between 10 and 50 MJup, in agreement with RV measurements. The dearth of objects in this mass range would naturally arise from the shape of the mass distribution, without the introduction of any distinct formation mechanism for BDs., 9 pages, 3 figures. Accepted for publication by Astronomy & Astrophysics
Published: 2015

50. Excess of rare coding variants in PLD3 in late-but not early-onset Alzheimer's disease

Author: Dan Rujescu, Eva C. Schulte, Harald Hampel, Juliane Winkelmann, Annette Peters, Janine Diehl-Schmid, Panagiotis Alexopoulos, Christian Gieger, Alexander Kurz, Institut für Humangenetik, Helmholtz-Zentrum München (HZM), Neurologische Klinik und Poliklinik, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Klinik und Poliklinik für Psychiatrie une Psychotherapie, Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), AXA Research Fund, Institut de la Mémoire et de la Maladie d'Alzheimer [Paris] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institute of Genetic Epidemiology, German Research Center for Environmental Health-Helmholtz-Zentrum München (HZM), Klinik für Psychiatrie, Martin-Luther-University Halle-Wittenberg, Munich Cluster for systems neurology [Munich] (SyNergy), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU), Department of nerology and neurosciences, Stanford University, Helmholtz Zentrum München = German Research Center for Environmental Health, Institut de la Mémoire et de la Maladie d'Alzheimer [CHU Pitié-Salpétriêre] (IM2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-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), and Administateur, HAL Sorbonne Université
Subjects: Genetics, business.industry, Odds ratio, Frontotemporal lobar degeneration, Disease, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Alzheimer's disease, medicine.disease, Biochemistry, Minor allele frequency, Text mining, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Cohort, Data Report, Medicine, Coding region, Early-onset Alzheimer's disease, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], business, Molecular Biology
Abstract: International audience; Recently, mutations in phospholipase D3 (PLD3) were reported in late-onset Alzheimer's disease (AD). By screening the coding regions of PLD3 for variants in a European cohort of 1,089 AD cases, 182 individuals with frontotemporal lobar degeneration and 1,456 controls, we identified 32 variants with a minor allele frequency
Published: 2015

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