1,915 results on '"Université Paris 06"'
Search Results
2. Influence of 4 preservation solutions on ICU stay, graft and patient survival following liver transplantation
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L. Barbier, Emmanuel Boleslawski, J.-M. Siksik, E. Savier, A. Mulliri, K. Boudjema, Gabriella Pittau, René Adam, O. Boilot, Jean-Yves Mabrut, A. Sepulveda, Astrid Herrero, G.-P. Pageaux, J.-L. Golmard, Christophe Laurent, Philippe Bachellier, F. Dondero, François Faitot, Emilie Gregoire, C. Salloum, E. Salame, Laurence Chiche, Jean Hardwigsen, Christian Letoublon, M. Rayar, R. Brustia, Philippe Compagnon, F. Jeune, Y.P. Le Treut, Jean Gugenheim, Samir Jaber, Bertrand Suc, Olivier Scatton, A. Mallet, J. Abba, P. Houssel-Debry, C. Maulat, E. Buc, C B Lim, F. Perdigao, Safi Dokmak, François-René Pruvot, M. Chirica, Oriana Ciacio, B. Trechot, G. Rousseau, S. Branchereau, C. Chardot, Pietro Addeo, K. Mohkam, Jean-Christophe Vaillant, Francis Navarro, A. Merdignac, T. Dao, Olivier Soubrane, Daniel Cherqui, B. Heyd, MORNET, Dominique, Service de Chirurgie Digestive, Hépato-Bilio-pancréatique et Transplantation Hépatique [CHU Pitié-Salpétrière], 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), Département de Biostatistiques [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Paul Brousse, Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], Service d’Hépatologie [Hôpital Beaujon], Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital de Hautepierre [Strasbourg], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi], Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Hôpital de la Timone [CHU - APHM] (TIMONE), Service de pédiatrie médicale et médecine de l'adolescent [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hôpital Henri Mondor, Centre Hospitalier Universitaire [Grenoble] (CHU), Département de chirurgie digestive et de l'urgence, CHU Grenoble-Hôpital Michallon, Hôpital Claude Huriez [Lille], CHU Lille, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Université Pierre et Marie Curie - Paris 6 (UPMC), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte (M2iSH), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital Bicêtre, CHU Necker - Enfants Malades [AP-HP], Agence de la Biomédecine, Service de chirurgie digestive et hépato-bilio-pancréatique [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], CHU Pitié Salpêtrière, CHU Pitié-Salpêtrière [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Unité de Transplantation, CHU Cochin [AP-HP], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, CHU Saint-Eloi-Université de Montpellier (UM), Department of Hepatobiliary Surgery, Hôpital Conception, Hôpital Claude Huriez, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Hôpital de Rangueil, CHU Toulouse [Toulouse], UPMC Université Paris 06, 75012 Paris, France., Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Mère Enfant Edouard Herriot, 69677 Bron, France. 2, Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte - Clermont Auvergne (M2iSH), Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne (UCA)-Centre de Recherche en Nutrition Humaine d'Auvergne (CRNH d'Auvergne), Université Clermont Auvergne, and Hôpital Bicêtre, AP-HP, 94275 Le Kremlin-Bicêtre, France.
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Male ,Adenosine ,[SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery ,medicine.medical_treatment ,[SDV]Life Sciences [q-bio] ,Liver transplantation ,Disaccharides ,Electrolytes ,0302 clinical medicine ,Glutamates ,Preservation solutions ,Insulin ,Mannitol ,Registries ,ComputingMilieux_MISCELLANEOUS ,Univariate analysis ,Graft Survival ,General Medicine ,Prognosis ,Glutathione ,Multicenter study ,030220 oncology & carcinogenesis ,030211 gastroenterology & hepatology ,Female ,Human ,medicine.medical_specialty ,Critical Care ,Allopurinol ,Organ Preservation Solutions ,[SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery ,03 medical and health sciences ,Raffinose ,Intensive care ,medicine ,Humans ,Icu stay ,Histidine ,Retrospective Studies ,business.industry ,Significant difference ,Retrospective cohort study ,Patient survival ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Length of Stay ,Survival Analysis ,Preservation solution ,[SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,Surgery ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,business ,Follow-Up Studies - Abstract
International audience; Objective - The goal of this study was to evaluate the prognostic role of four preservation solutions in liver transplantation (LT). Patients and methods - This is a retrospective study originating from 22 French centers performing LT, registered in the prospective databank of the Cristal Biomedicine Agency between 2008 and 2013. The preservation solutions used were Celsior (CS), Institut Georges Lopez (IGL)-1, Solution de Conservation des Organes et des Tissus (SCOT) 15 and University of Wisconsin (UW) solutions. Exclusion criteria were preservation with unknown or inhomogeneous solutions, or Histidine-tryptophan-ketoglutarate (HTK) solution (representing only 3% of LT). Patient survival was the main endpoint. Secondary endpoints were graft survival and duration of stay in intensive care. Results - Of 6347 LT performed, 4928 were included in this study, for which the distribution of preservation solution was CS (30%), IGL-1 (44%), SCOT 15 (10%) and UW (16%). Patient survival was 86%, 80% and 74% at 1, 3 and 5 years after LT, respectively, without any statistically significant difference between the four solutions (P=0.78). Graft survival was 82%, 75% and 69% at 1, 3 and 5 years after LT, respectively, without any statistically significant difference between the four solutions (P=0.80). Duration of intensive care was different according to the solution used in univariate analysis (P
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- 2020
3. High‐resolution wavelength‐dispersive spectroscopy of K‐shell transitions in hydrogen‐like gold
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Csilla I. Szabo, Wanqiu Chen, N. Petridis, S. Hagmann, R. Heß, K. S. Schulze, G. Weber, C. Dimopoulou, U. Spillmann, F. Nolden, Michael Lestinsky, S. Trotsenko, O. Wehrhan, D. Liesen, Ingo Uschmann, N. Winters, Renate Märtin, M. Schwemlein, T. Kämpfer, Alexandre Simionovici, K.-H. Blumenhagen, P. M. Hillenbrand, E. Ziegler, T. Gassner, Martino Trassinelli, C. Brandau, Dariusz Banaś, M. Steck, A. Gumberidze, Paul Indelicato, R. Loetzsch, M. S. Sanjari, Yu. A. Litvinov, Nicolas Winckler, F. Bosch, H. F. Beyer, Th. Stöhlker, Eckhart Förster, Danyal Winters, Robert E. Grisenti, B. Manil, Paweł P. Jagodziński, Helmholtz zentrum für Schwerionenforschung GmbH (GSI), Institut des Nanosciences de Paris (INSP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Agrégats et surfaces sous excitations intenses (INSP-E10), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Ottawa Research & Development Centre, Science & Technology Branch, Agriculture and Agri-Food [Ottawa] (AAFC), Laboratoire Kastler Brossel (LKB (Jussieu)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Institute of Physics [Kielce], Jan Kochanowski University, Laboratoire de Physique des Lasers (LPL), Université Paris 13 (UP13)-Centre National de la Recherche Scientifique (CNRS), Institut für Kernphysik, Goethe-Universität Frankfurt am Main, Laboratoire de Sciences de la Terre (LST), 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), Université Paris 06, X-ray Optics Croup Institute of Optics and Quantum Electronics, Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Agriculture and Agri-Food (AAFC), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), and École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL)
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Materials science ,Hydrogen ,[PHYS.PHYS.PHYS-ATOM-PH]Physics [physics]/Physics [physics]/Atomic Physics [physics.atom-ph] ,Analytical chemistry ,Electron shell ,chemistry.chemical_element ,High resolution ,01 natural sciences ,010305 fluids & plasmas ,Wavelength-dispersive X-ray spectroscopy ,chemistry ,0103 physical sciences ,010306 general physics ,Spectroscopy ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2019
4. Quantum reflection of antihydrogen from a liquid helium bulk
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Astrid Lambrecht, E. A. Kupriyanova, P.-P. Crépin, R. Guérout, Sergey Vasiliev, Serge Reynaud, Valery Nesvizhevsky, A. Yu. Voronin, Université Paris 06, Institut Laue-Langevin (ILL), ILL, Laboratoire Kastler Brossel (LKB (Jussieu)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), and Lomonosov Moscow State University (MSU)
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Physics ,Free fall ,Nuclear and High Energy Physics ,Annihilation ,010308 nuclear & particles physics ,Liquid helium ,Condensed Matter Physics ,7. Clean energy ,01 natural sciences ,Atomic and Molecular Physics, and Optics ,law.invention ,[PHYS.QPHY]Physics [physics]/Quantum Physics [quant-ph] ,Physics::Plasma Physics ,law ,0103 physical sciences ,Physics::Atomic and Molecular Clusters ,Physics::Atomic Physics ,Physical and Theoretical Chemistry ,Atomic physics ,010306 general physics ,Antihydrogen ,ComputingMilieux_MISCELLANEOUS ,Quantum reflection - Abstract
We study the quantum reflection of ultracold antihydrogen atoms bouncing on the surface of a liquid helium bulk. The Casimir-Polder potential and quantum reflection are calculated and compared to the same quantities for other bulks. Antihydrogen can be protected from annihilation for as long as 1.3 s on a bulk of liquid 4He, and 1.7 s for liquid 3He. These large lifetimes open interesting perspectives for spectroscopic measurements of the free fall acceleration of antihydrogen.
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- 2019
5. Persistent homology for object segmentation in multidimensional grayscale images
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Mohammad Kacim, Valeriu Vrabie, Alban Goupil, Thomas Boudier, Rabih Assaf, Centre de Recherche en Sciences et Technologies de l'Information et de la Communication - EA 3804 (CRESTIC), Université de Reims Champagne-Ardenne (URCA), IFR83, Université Paris 06, Mathématiques - Analyse, Probabilités, Modélisation - Orléans (MAPMO), and Centre National de la Recherche Scientifique (CNRS)-Université d'Orléans (UO)
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0301 basic medicine ,Computer science ,02 engineering and technology ,Algebraic topology ,Grayscale ,Image (mathematics) ,03 medical and health sciences ,[INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing ,Artificial Intelligence ,0202 electrical engineering, electronic engineering, information engineering ,Segmentation ,Independence (probability theory) ,ComputingMilieux_MISCELLANEOUS ,Sequence ,Persistent homology ,business.industry ,Pattern recognition ,Object (computer science) ,030104 developmental biology ,[MATH.MATH-AT]Mathematics [math]/Algebraic Topology [math.AT] ,[INFO.INFO-TI]Computer Science [cs]/Image Processing [eess.IV] ,Signal Processing ,020201 artificial intelligence & image processing ,Computer Vision and Pattern Recognition ,Artificial intelligence ,business ,Software - Abstract
In this paper, we develop a methodology originating from algebraic topology, and we demonstrate its capability of performing multidimensional object segmentation without the need of prior parameters. Persistent homology is a method used in algebraic topology to study qualitative features of data that persist across varying scales. The construction of a topological complex on the image is followed by a filtration scheme that consists of composing a nested sequence of cell complexes on which the persistent homology is computed. The most persistent homology classes are extracted by identifying 1D and 2D chains with large lifespans, which allows salient objects in 2D and 3D images to be segmented and detected. A comparison between this method and other segmentation techniques on a synthetic image shows the advantages of the proposed method. The strength of this technique is reflected in its insensitivity to continuous deformations and perturbations of the input function and in its independence of prior parameters. The results obtained on real and biomedical 2D and 3D images also demonstrate the potential of this method.
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- 2018
6. Shifting meiotic to mitotic spindle assembly in oocytes disrupts chromosome alignment
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Bennabi, Isma, Quéguiner, Isabelle, Kolano, Agnieszka, Boudier, Thomas, Mailly, Philippe, Verlhac, Marie-Hélène, Terret, Marie-Emilie, Centre interdisciplinaire de recherche en biologie (CIRB), Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), IFR83, Université Paris 06, Imagerie intégrative de la molécule à l'organisme, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Physiopathologie des Maladies du Système Nerveux Central, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Labex MemoLife, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Collège de France (CdF (institution))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and 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)
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HSET ,mitosis ,[SDV]Life Sciences [q-bio] ,meiosis ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,chromosome misalignment ,ComputingMilieux_MISCELLANEOUS ,spindle morphogenesis Subject Category Cell Cycle - Abstract
International audience; Mitotic spindles assemble from two centrosomes, which are major microtubule-organizing centers (MTOCs) that contain centrioles. Meiotic spindles in oocytes, however, lack centrioles. In mouse oocytes, spindle microtubules are nucleated from multiple acentri-olar MTOCs that are sorted and clustered prior to completion of spindle assembly in an "inside-out" mechanism, ending with establishment of the poles. We used HSET (kinesin-14) as a tool to shift meiotic spindle assembly toward a mitotic "outside-in" mode and analyzed the consequences on the fidelity of the division. We show that HSET levels must be tightly gated in meiosis I and that even slight overexpression of HSET forces spindle morphogenesis to become more mitotic-like: rapid spindle bipolarization and pole assembly coupled with focused poles. The unusual length of meio-sis I is not sufficient to correct these early spindle morphogenesis defects, resulting in severe chromosome alignment abnormalities. Thus, the unique "inside-out" mechanism of meiotic spindle assembly is essential to prevent chromosomal misalignment and production of aneuploidy gametes.
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- 2018
7. Sharing of mitotic pre-ribosomal particles between daughter cells
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Valentina Sirri, Nathalie Jourdan, Danièle Hernandez-Verdun, Pascal Roussel, 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 Paris Diderot - Paris 7 (UPD7), Photobiologie (PHOTO), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Jacques Monod (IJM (UMR_7592)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Centre National de la Recherche Scientifique, UPMC Université Paris 06, Université Paris Diderot, Université Paris Diderot - Paris 7 (UPD7)-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)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-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)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Bondidier, Martine
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0301 basic medicine ,Cell division ,Nucleolus ,Ribosome biogenesis ,Mitosis ,[SDV.BC]Life Sciences [q-bio]/Cellular Biology ,Biology ,03 medical and health sciences ,Cyclin-dependent kinase ,CDC2 Protein Kinase ,RNA Precursors ,Humans ,RNA Processing, Post-Transcriptional ,Telophase ,[SDV.BC] Life Sciences [q-bio]/Cellular Biology ,Cell Biology ,G1 Phase Cell Cycle Checkpoints ,Cell biology ,030104 developmental biology ,Ribosomal RNA ,RNA, Ribosomal ,Mitotic exit ,biology.protein ,Ribosomes ,Cell Nucleolus ,CDK inhibitor ,HeLa Cells ,PNB - Abstract
International audience; Ribosome biogenesis is a fundamental multistep process initiated by the synthesis of 90S pre-ribosomal particles in the nucleoli of higher eukaryotes. Even though synthesis of ribosomes stops during mitosis while nucleoli disappear, mitotic pre-ribosomal particles persist as observed in pre-nucleolar bodies (PNBs) during telophase. To further understand the relationship between the nucleolus and the PNBs, the presence and the fate of the mitotic pre-ribosomal particles during cell division were investigated. We demonstrate that the recently synthesized 45S precursor ribosomal RNAs (pre-rRNAs) as well as the 32S and 30S pre-rRNAs are maintained during mitosis and associated with the chromosome periphery together with pre-rRNA processing factors. Maturation of the mitotic pre-ribosomal particles, as assessed by the stability of the mitotic pre-rRNAs, is transiently arrested during mitosis by a cyclin-dependent kinase (CDK)1-cyclin-B-dependent mechanism and can be restored by CDK inhibitor treatments. At the M-G1 transition, the resumption of mitotic pre-rRNA processing in PNBs does not induce the disappearance of PNBs; this only occurs when functional nucleoli reform. Strikingly, during their maturation process, mitotic pre-rRNAs localize in reforming nucleoli.
- Published
- 2016
8. Predicting CHD risk in France: a pooled analysis of the D.E.S.I.R., Three City, PRIME, and SU.VI.MAX studies
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Muriel Tafflet, Jean Philippe Empana, Michèle Montaye, Sébastien Czernichow, S Bineau, Jean-Bernard Ruidavets, Sylvie Escolano, Pierre Ducimetière, Beverley Balkau, Bernadette Haas, AC Vergnaux, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S 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)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National de la Recherche Agronomique (INRA), INSERM, U708, Université Paris 06, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Université Lille Nord de France (COMUE), Université de Strasbourg (UNISTRA), Dept Publ Hlth, Universiteit Gent = Ghent University [Belgium] (UGENT), Fondation pour la Recherche Medicale, Caisse Nationale Maladie des Travailleurs Salaries, Direction Generale de la Sante, MGEN, Institut de la Longevite, Conseils Regionaux of Aquitaine and Bourgogne, Fondation de France, Ministry of Research, INSERM contracts with CNAMTS [Caisse Nationale d'Assurance Maladie de Travailleurs Salaries (French National Health Insurance Agency for Wage Earners)], Lilly Novartis Pharma, sanofi-aventis, INSERM (Reseaux en Sante Publique, Interactions entre les determinants de la sante, Cohortes Sante TGIR), Association Diabete Risque Vasculaire, Federation Francaise de Cardiologie, La Fondation de France, ALFEDIAM, ONIVINS, Ardix Medical, Bayer Diagnostics, Becton Dickinson, Cardionics, Merck Sante, NovoNordisk, Pierre Fabre, Roche, and Topcon
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Male ,MULTIPLE BIOMARKERS ,Pediatrics ,Time Factors ,Epidemiology ,[SDV]Life Sciences [q-bio] ,10-YEAR RISK ,Coronary Disease ,Kaplan-Meier Estimate ,030204 cardiovascular system & hematology ,risk prediction ,0302 clinical medicine ,FRAMINGHAM ,Multicenter Studies as Topic ,risk factors ,Medicine ,030212 general & internal medicine ,Family history ,10. No inequality ,POPULATION ,Randomized Controlled Trials as Topic ,2. Zero hunger ,Framingham Risk Score ,MEN ,Middle Aged ,Prognosis ,3. Good health ,Coronary heart disease ,CARDIOVASCULAR-DISEASE ,Disease Progression ,Population study ,Female ,France ,Cardiology and Cardiovascular Medicine ,Risk assessment ,Algorithms ,medicine.medical_specialty ,Waist ,Risk Assessment ,VALIDATION ,03 medical and health sciences ,Humans ,CORONARY-HEART-DISEASE ,COHORT ,Aged ,Proportional Hazards Models ,business.industry ,Proportional hazards model ,Reproducibility of Results ,Asymptomatic Diseases ,FOLLOW-UP ,business ,Body mass index ,Demography - Abstract
International audience; Background: We aimed to develop and validate a simple coronary heart disease (CHD) risk algorithm applicable to asymptomatic men and women in France, and to compare its accuracy with that of the last published version of the Framingham risk function for cardiovascular disease. Design: A pooled analysis of four French prospective general-population studies. Methods: The baseline and follow-up data from D.E.S.I.R., PRIME, Three City, and SU.VI.MAX studies were used. The 10-year CHD risk was estimated by the Cox proportional hazards model with candidate variables including age, gender, body mass index, waist circumference, family history of coronary heart disease, smoking status, diabetes status, systolic blood pressure, and total and high-density lipoprotein (HDL) cholesterol. Results: The study population included 22,256 subjects (61.4% men) aged (SD) 56.0 years (8.3) without a personal history of CHD at baseline. After a mean follow-up of 8.0 years (2.3), 788 first CHD events occurred, 726 in men and 62 in women. The final model included age, gender, age x gender interaction, current smoking status, diabetes status, systolic blood pressure, total and HDL cholesterol. Using this model, the number of predicted coronary events fitted that given by the 10-year Kaplan-Meier survival estimates within each decile of estimated risk (calibration). This model had fair discrimination: Harrell C-index, 0.7831 (95% CI: 0.7704-0.7957). For comparison, the recalibrated Framingham risk function had equivalent performances compared to the French risk equation. Conclusion: Our 10-year French CHD risk equation based on traditional risk factors performed at least as well as the recalibrated Framingham cardiovascular disease risk function.
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- 2011
9. Mitotic index, microvascular proliferation, and necrosis define 3 groups of 1p/19q codeleted anaplastic oligodendrogliomas associated with different genomic alterations
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Dominique, Figarella-Branger, Karima, Mokhtari, Caroline, Dehais, Anne, Jouvet, Emmanuelle, Uro-Coste, Carole, Colin, Catherine, Carpentier, Fabien, Forest, Claude-Alain, Maurage, Jean-Michel, Vignaud, Marc, Polivka, Emmanuelle, Lechapt-Zalcman, Sandrine, Eimer, Gabriel, Viennet, Isabelle, Quintin-Roué, Marie-Hélène, Aubriot-Lorton, Marie-Danièle, Diebold, Delphine, Loussouarn, Catherine, Lacroix, Valérie, Rigau, Annie, Laquerrière, Fanny, Vandenbos, Sophie, Michalak, Henri, Sevestre, Michel, Peoch, François, Labrousse, Christo, Christov, Jean-Louis, Kemeny, Marie-Pierre, Chenard, Danchristian, Chiforeanu, François, Ducray, Ahmed, Idbaih, Frederic, Dhermain, Laboratoire d'anatomie pathologique - [Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital Nord [CHU - APHM], Centre de Recherches en Oncologie biologique et Oncopharmacologie (CRO2), Aix Marseille Université (AMU)- Hôpital de la Timone [CHU - APHM] (TIMONE)-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), Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière (CRICM), 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), Centre de Pathologie et de Neuropathologie Est, Hospices Civils de Lyon (HCL), Service d'anatomie pathologique et histologie-cytologie [Rangueil], Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre de Recherches en Cancérologie de Toulouse (CRCT), 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), INSERM, U975, Université Paris 06, Service d’Anatomie et Cytologie Pathologiques, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Service d'Anatomie Pathologique, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service d’Anatomie Pathologique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'anatomie et cytologie pathologiques, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Laboratoire d'Anatomie Pathologique [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Hypoxie, physiopathologies cérébrovasculaire et tumorale (CERVOxy), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Service de Pathologie-Neuropathologie, CHU de Bordeaux Pellegrin [Bordeaux], Histologie et Pathologie Moléculaire, Université Bordeaux Segalen - Bordeaux 2, Service Anatomie et Cytologie Pathologiques, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), CHRU Brest - Laboratoire d'Anatomo-Pathologie (CHU - AnaPath), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de Pathologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire d'anatomie et cytologie pathologiques [Reims], Centre Hospitalier Universitaire de Reims (CHU Reims), Service d'Anatomie Pathologique B, Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'Anatomie et Cytologie Pathologique, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Laboratoire d'Anatomie et Cytologie Pathologiques, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service d'Anatomie et Cytologie Pathologique [CHU Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), chu de nice, Hôpital Pasteur, Laboratoire Central d’Anatomo Pathologie, Hôpital Pasteur [Nice] (CHU), Département de pathologie cellulaire et tissulaire, CHU d'Angers, 4, rue Larrey, 49100 Angers, France., Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service d'Anatomie et Cytologie Pathologiques, CHU Amiens-Picardie, Service d'Anatomie Pathologique [CHU Limoges], CHU Limoges, Hôpital Henri Mondor, CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Laboratoire d'anatomie pathologique - Hôpital de Hautepierre Hôpitaux Universitaires de Strasbourg - Université de Strasbourg, Service d'anatomie et cytologie pathologiques [Rennes] = Anatomy and Cytopathology [Rennes], CHU Pontchaillou [Rennes], Service de neuro-oncologie [Hôpital Pierre Wertheimer - HCL], Hôpital neurologique et neurochirurgical Pierre Wertheimer [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de recherche en neurosciences de Lyon - Lyon Neuroscience Research Center (CRNL), 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), Service de Neuropathologie Raymond Escourolle [CHU Pitié Salpêtrière], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de neurologie 2 [CHU Pitié-Salpêtrière], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], 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), CHU Saint-Etienne, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Service d'Anatomie et Cytologie Pathologique [Rouen], AP-HP Hôpital Henri Mondor (Créteil), Service d'anatomie et cytologie pathologiques [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Centre de recherche en neurosciences de Lyon (CRNL), 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), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Lariboisière-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service de Neuropathologie [CHU Pitié Salpêtrière], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Nord [CHU - APHM]-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM), Centre National de la Recherche Scientifique (CNRS)-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), Institut National de la Santé et de la Recherche Médicale (INSERM)- Hôpital de la Timone [CHU - APHM] (TIMONE)-Aix Marseille Université (AMU), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université
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Cancer Research ,Pathology ,medicine.medical_specialty ,IDH1 ,Necrosis ,Mitotic index ,Proliferation index ,[SDV]Life Sciences [q-bio] ,Oligodendroglioma ,Biology ,Disease-Free Survival ,03 medical and health sciences ,0302 clinical medicine ,Chromosome instability ,medicine ,Mitotic Index ,Humans ,Progression-free survival ,ComputingMilieux_MISCELLANEOUS ,Neovascularization, Pathologic ,Brain Neoplasms ,Brain ,medicine.disease ,Isocitrate Dehydrogenase ,3. Good health ,Oncology ,Chromosomes, Human, Pair 1 ,030220 oncology & carcinogenesis ,Basic and Translational Investigations ,Chromosome abnormality ,Neurology (clinical) ,medicine.symptom ,Chromosome Deletion ,Chromosomes, Human, Pair 19 ,030217 neurology & neurosurgery - Abstract
BACKGROUND: The aim of this study was to correlate histological features and molecular characteristics in anaplastic oligodendrogliomas (AO). METHODS: The histological characteristics of 203 AO patients enrolled in the French national network POLA were analyzed. The genomic profiles of 191 cases were studied using genomic arrays. IDH mutational status was assessed by immunohistochemistry and direct sequencing. RESULTS: 1p/19q co-deletion was present in 79% of cases and was associated with alpha-internexin expression (p < 10-4), IDH1/2 mutation (p < 10-4), chromosome 4 loss (p < 10-3), and better overall survival (p < 10-4). Based on mitotic index, microvascular proliferation (MVP) and necrosis, 3 groups of 1p/19q co-deleted AO were identified: AO with more than 5 mitoses per 10-HPF, no MVP and no necrosis, (1), AO with MVP and no necrosis (2) and AO with MVP and necrosis (3). Compared to group 1, group 2 and 3 AO had a higher mean Ki-67 proliferation index and a higher rate of 9p and 9q losses. Compared to group 2, group 3 AO had a higher number of chromosomal alterations including chromosome 4 loss. In the subgroup of 157 1p/19q co-deleted AO, chromosomal instability was associated with shorter progression free survival (p = 0.024) and shorter overall survival (p = 0.023). CONCLUSIONS: The present study shows that oligodendroglioma with classic histological features remains a molecularly heterogeneous entity and should be stratified according to 1p/19q status because of its major prognostic relevance. Moreover, 1p/19q co-deleted AO are also heterogeneous. Interestingly, mitotic index, MVP and necrosis help to classify them into three groups associated with distinct genomic alterations.
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- 2014
10. The pleiotropic movement disorders phenotype of adult ataxia-telangiectasia
- Author
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Michel Koenig, Aurélie Méneret, Nizar Mahlaoui, Marc-Henri Stern, Catherine Dubois d'Enghien, Emmanuelle Apartis, Alexandra Durr, Felipe Suarez, Guillaume Rieunier, Sophie Rivaud-Péchoux, Bertrand Gaymard, Thierry Maisonobe, Marie Vidailhet, Dominique Stoppa-Lyonnet, Bertrand Degos, David Grabli, Alain Fischer, Baya Benyahia, Mathieu Anheim, Yara Ahmar-Beaugendre, Christine Tranchant, Assistance Publique-Hôpitaux de Paris, Service d'Immunologie et d'Hématologie Pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Neurophysiologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Les chimiokines et leurs récepteurs : fonctions cérébrales et neuroendocriniennes, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Neurologie [Strasbourg], CHU Strasbourg-Hopital Civil, 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), Service de Neuroradiologie [CHU Pitié-Salpêtrière], Thérapie des maladies du muscle strié, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), INSERM, U975, Université Paris 06, Neurologie et thérapeutique expérimentale, Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR70-Université Pierre et Marie Curie - Paris 6 (UPMC), Institut Curie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), and Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR70-Institut National de la Santé et de la Recherche Médicale (INSERM)
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Adult ,Male ,Myoclonus ,medicine.medical_specialty ,Pathology ,Movement disorders ,Ataxia ,[SDV]Life Sciences [q-bio] ,Mutation, Missense ,Immunoglobulins ,Ataxia Telangiectasia Mutated Proteins ,Gastroenterology ,Severity of Illness Index ,Cohort Studies ,03 medical and health sciences ,Dysarthria ,Ataxia Telangiectasia ,Young Adult ,0302 clinical medicine ,Ocular Motility Disorders ,Internal medicine ,Chromosomal Instability ,medicine ,Missense mutation ,Humans ,Oculomotor apraxia ,Age of Onset ,Mobility Limitation ,Eye Movement Measurements ,030304 developmental biology ,Dystonia ,0303 health sciences ,Movement Disorders ,Genetic Pleiotropy ,medicine.disease ,3. Good health ,Phenotype ,Ataxia-telangiectasia ,Disease Progression ,Female ,Neurology (clinical) ,alpha-Fetoproteins ,medicine.symptom ,Psychology ,030217 neurology & neurosurgery - Abstract
International audience; OBJECTIVE:To assess the clinical spectrum of ataxia-telangiectasia (A-T) in adults, with a focus on movement disorders.METHODS:A total of 14 consecutive adults with A-T were included at 2 tertiary adult movement disorders centers and compared to 53 typical patients with A-T. Clinical evaluation, neurophysiologic and video-oculographic recording, imaging, laboratory investigations, and ATM analysis were performed.RESULTS:In comparison with typical A-T cases, our patients demonstrated later mean age at onset (6.1 vs 2.5 years, p < 0.0001), later loss of walking ability (p = 0.003), and longer survival (p = 0.0039). The presenting feature was ataxia in 71% and dysarthria and dystonia in 14% each. All patients displayed movement disorders, among which dystonia and subcortical myoclonus were the most common (86%), followed by tremor (43%). Video-oculographic recordings revealed mostly dysmetric saccades and 46% of patients had normal latencies (i.e., no oculomotor apraxia) and velocities. The α-fetoprotein (AFP) level was normal in 7%, chromosomal instability was found in 29% (vs 100% of typical patients, p = 0.0006), and immunoglobulin deficiency was found in 29% (vs 69%, p = 0.057). All patients exhibited 2 ATM mutations, including at least 1 missense mutation in 79% of them (vs 36%, p = 0.0067).CONCLUSION:There is great variability of phenotype and severity in A-T, including a wide spectrum of movement disorders. Karyotype and repeated AFP level assessments should be performed in adults with unexplained movement disorders as valuable clues towards the diagnosis. In case of a compatible phenotype, A-T should be considered even if age at onset is late and progression is slow
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- 2014
11. Multi-user quantum key distribution with entangled photons from an AlGaAs chip
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Adeline Orieux, Eleni Diamanti, Sara Ducci, Aristide Lemaître, C. Gomez-Carbonell, Isabelle Zaquine, Claire Autebert, Julien Trapateau, Université Paris 06, Laboratoire de Photophysique Moléculaire (PPM), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11), Laboratoire de photonique et de nanostructures (LPN), Centre National de la Recherche Scientifique (CNRS), Laboratoire Traitement et Communication de l'Information (LTCI), and Télécom ParisTech-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS)
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Quantum Physics ,Quantum network ,Photon ,Physics and Astronomy (miscellaneous) ,Computer science ,Materials Science (miscellaneous) ,FOS: Physical sciences ,Key distribution ,Quantum channel ,Quantum key distribution ,01 natural sciences ,Multiplexer ,Atomic and Molecular Physics, and Optics ,3. Good health ,010309 optics ,Photon entanglement ,[PHYS.QPHY]Physics [physics]/Quantum Physics [quant-ph] ,0103 physical sciences ,Electronic engineering ,Electrical and Electronic Engineering ,Quantum information ,Quantum Physics (quant-ph) ,010306 general physics ,ComputingMilieux_MISCELLANEOUS - Abstract
In view of real world applications of quantum information technologies, the combination of miniature quantum resources with existing fibre networks is a crucial issue. Among such resources, on-chip entangled photon sources play a central role for applications spanning quantum communications, computing and metrology. Here, we use a semiconductor source of entangled photons operating at room temperature in conjunction with standard telecom components to demonstrate multi-user quantum key distribution, a core protocol for securing communications in quantum networks. The source consists of an AlGaAs chip emitting polarization entangled photon pairs over a large bandwidth in the main telecom band around 1550 nm without the use of any off-chip compensation or interferometric scheme; the photon pairs are directly launched into a dense wavelength division multiplexer (DWDM) and secret keys are distributed between several pairs of users communicating through different channels. We achieve a visibility measured after the DWDM of 87% and show long-distance key distribution using a 50-km standard telecom fibre link between two network users. These results illustrate a promising route to practical, resource-efficient implementations adapted to quantum network infrastructures., Comment: 13 pages, 5 figures, 2 tables
- Published
- 2016
12. The Gbar project, or how does antimatter fall?
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M. Staszczak, Jean-Michel Rey, J. Trapateau, Laszlo Liszkay, Paul Indelicato, Paul-Antoine Hervieux, Romain Guérout, Vladimir Manea, P. Debu, B. Rossi, Serge Reynaud, V.-Q. Tran, A. Douillet, P. Perez, A. Mohri, H. A. Torii, Jean-Philippe Karr, F. Nez, François Biraben, Alexei Voronin, S. Guellati, Laurent Hilico, P.Froelich, Jochen Walz, B. Vallage, D. Lunney, P. Dupre, A. Badertscher, Sebastian Wolf, Giovanni Manfredi, Astrid Lambrecht, A. Marchionni, M. Charlton, Paolo Crivelli, Y. Sacquin, P. Grandemange, Pierre Cladé, Naofumi Kuroda, N. Ruiz, S. Wronka, P. Comini, A. Curioni, Stefan Eriksson, Csilla I. Szabo, Yasunori Yamazaki, G. Chardin, B. Reymond, Gabriel Dufour, Bruno Mansoulie, Valery Nesvizhevsky, Niels Madsen, Ferdinand Schmidt-Kaler, D. G. Brook-Roberge, André Rubbia, D. P. van der Werf, Yasuyuki Nagashima, CSNSM SNO, Centre de Spectrométrie Nucléaire et de Spectrométrie de Masse (CSNSM), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Centre de Sciences Nucléaires et de Sciences de la Matière (CSNSM), Université Paris-Sud - Paris 11 (UP11)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Département des Accélérateurs, de Cryogénie et de Magnétisme (ex SACM) (DACM), Institut de Recherches sur les lois Fondamentales de l'Univers (IRFU), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, Université Paris 06, Université d'Évry-Val-d'Essonne (UEVE), Institut de Physique et Chimie des Matériaux de Strasbourg (IPCMS), Université de Strasbourg (UNISTRA)-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), Uppsala Univ, Dept Phys & Astron, Uppsala, SWEDEN, Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Sud - Paris 11 (UP11)-Centre de Sciences Nucléaires et de Sciences de la Matière (CSNSM), Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Paris-Sud - Paris 11 (UP11), Université de Strasbourg (UNISTRA)-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)
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Free fall ,IONS ,Nuclear and High Energy Physics ,Sympathetic cooling ,Physics::General Physics ,ANTIHYDROGEN ,MASS ,ACCELERATION ,[PHYS.NEXP]Physics [physics]/Nuclear Experiment [nucl-ex] ,7. Clean energy ,Gravitation ,Nuclear physics ,ATOMS ,Gravitational field ,GRAVITY ,Quantum mechanics ,Physics::Atomic and Molecular Clusters ,Physics::Atomic Physics ,Physical and Theoretical Chemistry ,Antihydrogen ,Physics ,Condensed Matter::Quantum Gases ,[PHYS]Physics [physics] ,SPECTROSCOPY ,PLASMA ,FIELD Free fall ,Condensed Matter Physics ,Atomic and Molecular Physics, and Optics ,Antiproton ,Antimatter ,Weak equivalence principle ,ANTIGRAVITY ,Quantum reflection - Abstract
International audience; The Einstein classical Weak Equivalence Principle states that the trajectory of a particle is independent of its composition and internal structure when it is only submitted to gravitational forces. This fundamental principle has never been directly tested with antimatter. However, theoretical models such as supergravity may contain components inducing repulsive gravity, thus violating this principle. The GBAR project (Gravitational Behaviour of Antihydrogen at Rest) proposes to measure the free fall acceleration of ultracold neutral antihydrogen atoms in the terrestrial gravitational field. The experiment consists in preparing antihydrogen ions (one antiproton and two positrons) and sympathetically cool them with Be+ ions to a few 10 mu K. The ultracold ions will then be photoionized just above threshold, and the free-fall time over a known distance measured. In this work, the GBAR project is described as well as possible improvements that use quantum reflection of antihydrogen on surfaces to use quantum methods of measurements.
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- 2013
13. Multiple binding of repressed mRNAs by the P-body protein Rck/p54
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Sylvie Souquere, Michèle Ernoult-Lange, Philippe Andrey, Thomas Boudier, Maryannick Harper, Nancy Standart, Michel Kress, Sonia Baconnais, Dominique Weil, Nicola Minshall, Eric Le Cam, Gérard Pierron, Marianne Bénard, Biologie de l'ARN (RnBi), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Interactions moléculaires et cancer (IMC (UMR 8126)), Signalisation, noyaux et innovations en cancérologie (UMR8126), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Dept Biochem, Université de Cambridge, Rétrovirus endogènes et éléments rétroides des eucaryotes supérieurs (REERES (UMR 8122)), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie Intégrative (IFR-BI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Jean-Pierre Bourgin (IJPB), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Ligue Nationale Contre le Cancer, Association pour la Recherche sur le Cancer, Royal Society/CNRS, CNRS, University Pierre et Marie Curie, IFR83, Université Paris 06, Compartimentation et trafic intracellulaire des mRNP = Compartmentation and intracellular traffic of mRNPs (LBD-E14), Laboratoire de Biologie du Développement [Paris] (LBD), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Interfaces biomatériaux/tissus hôtes, Université de Reims Champagne-Ardenne (URCA)-IFR53-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy (IGR), University of Cambridge [UK] (CAM), Génétique moléculaire et intégration des fonctions cellulaires (GMIFC), Centre National de la Recherche Scientifique (CNRS), Ligue nationale contre le cancer Fondation ARC pour la Recherche sur le CancerAustralian Research CouncilEuropean Commission Royal Society of LondonCentre National de la Recherche Scientifique (CNRS) Centre National de la Recherche Scientifique (CNRS)European Commission University Pierre et Marie Curie UK Research & Innovation (UKRI)Biotechnology and Biological Sciences Research Council (BBSRC)BB/C514766/1, Laboratoire de Biologie du Développement (LBD), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), 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)-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)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), 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)-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), CNRS FRE 3402, Centre National de la Recherche Scientifique (CNRS)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11), Biologie intégrative (FRBI), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)
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Untranslated region ,[SDV.SA]Life Sciences [q-bio]/Agricultural sciences ,[SDV]Life Sciences [q-bio] ,DEAD-box RNA Helicases ,STORED MRNP PARTICLES ,Adenosine Triphosphate ,mRNA decay ,MESH: Adenosine Triphosphate ,[PHYS]Physics [physics] ,0303 health sciences ,CPEB ,biology ,MESH: Protein Multimerization ,DEAD-box ,030302 biochemistry & molecular biology ,GRANULES ,LOCALIZATION ,Cell biology ,Protein Binding ,DEAD box ,Repressor ,Models, Biological ,Article ,03 medical and health sciences ,mRNA storage ,DEAD BOX HELICASE ,Proto-Oncogene Proteins ,DDX6 ,TRANSLATIONAL REPRESSION ,Humans ,MESH: DEAD-box RNA Helicases ,MESH: Protein Binding ,Protein Interaction Domains and Motifs ,RNA, Messenger ,Molecular Biology ,MESH: RNA, Messenger ,030304 developmental biology ,MESH: Protein Interaction Domains and Motifs ,Messenger RNA ,C-TERMINAL DOMAIN ,MESH: Humans ,COMPLEX ,P54 ,C-terminus ,MESH: Models, Biological ,RNA ,masking ,Molecular biology ,MESH: Proto-Oncogene Proteins ,Decapping complex ,MESH: HeLa Cells ,biology.protein ,Protein Multimerization ,HeLa Cells - Abstract
International audience; Translational repression is achieved by protein complexes that typically bind 3′ UTR mRNA motifs and interfere with the formation of the cap-dependent initiation complex, resulting in mRNPs with a closed-loop conformation. We demonstrate here that the human DEAD-box protein Rck/p54, which is a component of such complexes and central to P-body assembly, is in considerable molecular excess with respect to cellular mRNAs and enriched to a concentration of 0.5 mM in P-bodies, where it is organized in clusters. Accordingly, multiple binding of p54 proteins along mRNA molecules was detected in vivo. Consistently, the purified protein bound RNA with no sequence specificity and high nanomolar affinity. Moreover, bound RNA molecules had a relaxed conformation. While RNA binding was ATP independent, relaxing of bound RNA was dependent on ATP, though not on its hydrolysis. We propose that Rck/p54 recruitment by sequence-specific translational repressors leads to further binding of Rck/p54 along mRNA molecules, resulting in their masking, unwinding, and ultimately recruitment to P-bodies. Rck/p54 proteins located at the 5′ extremity of mRNA can then recruit the decapping complex, thus coupling translational repression and mRNA degradation.
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- 2012
14. Penetrance of Parkinson disease in glucocerebrosidase gene mutation carriers
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Christel Condroyer, Mathieu Anheim, Bernard Bonaiti, Alexandra Durr, Pierre Pollak, Alexis Brice, Alexis Elbaz, Suzanne Lesage, Catherine Bonaïti-Pellié, François Viallet, INSERM, U975, Université Paris 06, 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], CHU Pitié-Salpêtrière [APHP], INSERM, U708, UMR S708, Dept Neurol, Syngenta, Génétique Animale et Biologie Intégrative (GABI), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Troubles du comportement alimentaire de l'adolescent (UMR_S 669), Université Paris-Sud - Paris 11 (UP11)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Agence Nationale de la Recherche-Eranet Neuron [ANR-08-NEUR-004-01/R08200DS], Agence Nationale de la Recherche (France), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [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)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AgroParisTech-Institut National de la Recherche Agronomique (INRA), 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), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
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Proband ,Adult ,Male ,[SDV.SA]Life Sciences [q-bio]/Agricultural sciences ,Genetic counseling ,Penetrance ,Disease ,Biology ,Gene mutation ,03 medical and health sciences ,0302 clinical medicine ,Humans ,Genetic Predisposition to Disease ,Risk factor ,Parkinson Disease/genetics ,030304 developmental biology ,Aged ,Genetics ,RISK ,0303 health sciences ,Parkinson Disease ,Middle Aged ,ddc:616.8 ,Phenotype ,Mutation (genetic algorithm) ,Glucosylceramidase/genetics ,Mutation ,Glucosylceramidase ,Female ,Neurology (clinical) ,Glucocerebrosidase ,030217 neurology & neurosurgery - Abstract
Objective: Glucocerebrosidase (GBA) gene mutations represent a strong risk factor for Parkinson disease (PD). PD penetrance in GBA mutation carriers, which represents a key issue for genetic counseling, especially for relatives of patients with Gaucher disease (GD), is unknown. Our objective was to estimate PD penetrance in a familial study of GBA mutation carriers. Methods: Probands with familial PD were recruited through the French Parkinson Disease Genetic Study Group. All GBA exons were sequenced in probands and their relatives. To estimate the age-specific cumulative PD risk (i.e., penetrance) in GBA mutation carriers, we used the proband's phenotype exclusion likelihood method and corrected for selection of familial cases by considering the status of one affected relative per family as unknown. Results: Of 525 probands with familial PD, 24 (4.6%) were GBA mutation carriers. Of their 256 relatives, 43 (16.8%) had PD and 26 of 32 affected relatives tested for GBA mutations were mutation carriers; 213 relatives did not have PD and 31 of 71 of unaffected relatives tested for GBA mutations were mutation carriers. Under a dominant model, penetrance was estimated as 7.6%, 13.7%, 21.4%, and 29.7% at 50, 60, 70, and 80 years, respectively. There was no significant difference in penetrance at 70 years between N370S carriers, L444P carriers, and carriers of rarer mutations. Conclusion: The relatively high penetrance estimate in GBA carriers obtained in this study should lead to consideration of GBA as a dominant causal gene with reduced penetrance and should be taken into account for genetic counseling in relatives of patients with GD and patients with GBA-associated PD. Neurology (R) 2012; 78: 417-420
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- 2012
15. ColVI myopathies: where do we stand, where do we go?
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Gisèle Bonne, Tanya Stojkovic, Valérie Allamand, Susana Quijano-Roy, Pascale Richard, Laura Briñas, Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Thérapie des maladies du muscle strié, 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), Institut de Myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de pédiatrie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Raymond Poincaré [AP-HP], This study was funded by the Institut National de la Santé et de la Recherche Médicale (Inserm), Association Française contre les Myopathies (AFM), UPMC Université Paris 06, Centre National de la Recherche Scientifique (CNRS), Assistance Publique-Hôpitaux de Paris (AP-HP)., BMC, Ed., Service de Biochimie Métabolique [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), Centre de référence des maladies rares neuromusculaires [CHU Pitié-Salpétriêre], Centre de référence des maladies rares neuromusculaires, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)
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lcsh:Diseases of the musculoskeletal system ,Ullrich congenital muscular dystrophy ,Nonsense mutation ,Review ,Biology ,Bioinformatics ,03 medical and health sciences ,0302 clinical medicine ,Collagen VI ,medicine ,Orthopedics and Sports Medicine ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Muscular dystrophy ,Myopathy ,Molecular Biology ,Loss function ,030304 developmental biology ,Genetics ,0303 health sciences ,Bethlem myopathy ,Cell Biology ,medicine.disease ,3. Good health ,Congenital muscular dystrophy ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,medicine.symptom ,lcsh:RC925-935 ,030217 neurology & neurosurgery - Abstract
Collagen VI myopathies, caused by mutations in the genes encoding collagen type VI (ColVI), represent a clinical continuum with Ullrich congenital muscular dystrophy (UCMD) and Bethlem myopathy (BM) at each end of the spectrum, and less well-defined intermediate phenotypes in between. ColVI myopathies also share common features with other disorders associated with prominent muscle contractures, making differential diagnosis difficult. This group of disorders, under-recognized for a long time, has aroused much interest over the past decade, with important advances made in understanding its molecular pathogenesis. Indeed, numerous mutations have now been reported in the COL6A1, COL6A2 and COL6A3 genes, a large proportion of which are de novo and exert dominant-negative effects. Genotype-phenotype correlations have also started to emerge, which reflect the various pathogenic mechanisms at play in these disorders: dominant de novo exon splicing that enables the synthesis and secretion of mutant tetramers and homozygous nonsense mutations that lead to premature termination of translation and complete loss of function are associated with early-onset, severe phenotypes. In this review, we present the current state of diagnosis and research in the field of ColVI myopathies. The past decade has provided significant advances, with the identification of altered cellular functions in animal models of ColVI myopathies and in patient samples. In particular, mitochondrial dysfunction and a defect in the autophagic clearance system of skeletal muscle have recently been reported, thereby opening potential therapeutic avenues.
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- 2011
16. The size of the proton and the deuteron
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J.F.C.A. Veloso, Satish Dhawan, Livia Ludhova, François Nez, Lucile Julien, Catherine Schwob, Yi-Wei Liu, Randolf Pohl, Paul Indelicato, Joaquim M. F. dos Santos, João Cardoso, Franz Kottmann, D. S. Covita, L.M.P. Fernandes, David Taqqu, C.M.B. Monteiro, Andreas Dax, J. A. M. Lopes, Paul E. Knowles, F. D. Amaro, Aldo Antognini, Thomas Graf, Karsten Schuhmann, Lukas A. Schaller, Eric-Olivier Le Bigot, Tobias Nebel, Françoise Mulhauser, Cheng-Yang Kao, Paul Rabinowitz, Adolf Giesen, Theodor W. Hänsch, François Biraben, Technische Universität Dresden = Dresden University of Technology (TU Dresden), Universidade do Estado do Rio de Janeiro [Rio de Janeiro] (UERJ), Max-Planck-Institut für Quantenoptik (MPQ), Max-Planck-Gesellschaft, Université Paris 06, Faculdade de Engenharia da Universidade do Porto (FEUP), Universidade do Porto, Departamento de Fisica [Aveiro], Universidade de Aveiro, Ecole Polytechnique Fédérale de Lausanne (EPFL), Physics Department, Yale University [New Haven], Departamento de Física, University of Coimbra [Portugal] (UC), Institut für Strahwerkzeuge (IFSW), Stuttgart University, Laboratoire d'Economie et de Gestion (LEG), Université de Bourgogne (UB)-Centre National de la Recherche Scientifique (CNRS), National Tsing Hua University [Hsinchu] (NTHU), Laboratoire Kastler Brossel (LKB (Jussieu)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Institut d'Électronique et des Technologies du numéRique (IETR), Nantes Université (NU)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Centro de Quimica Estrutural (CQE), Instituto Superior Técnico, Universidade Técnica de Lisboa (IST), Département de Physique (dpuf), Albert-Ludwigs-Universität Freiburg, Department of Chemistry, Princeton University, Institut des Nanosciences de Paris (INSP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Paul Scherrer Institute (PSI), Institut fur Teilchenphysik [Zürich], Eidgenössische Technische Hochschule - Swiss Federal Institute of Technology [Zürich] (ETH Zürich), Technische Universität Dresden ( TUD ), Universidade do Estado do Rio de Janeiro, UERJ, Max-Planck-Institut für Quantenoptik ( MPQ ), Max-Planck-Institut, Faculdade de Engenharia [Porto] ( FEUP ), Universidade do Porto [Porto], Ecole Polytechnique Fédérale de Lausanne ( EPFL ), Université Yale - New Haven, University of Coimbra [Portugal] ( UC ), Institut für Strahwerkzeuge ( IFSW ), Laboratoire d'Economie et de Gestion ( LEG ), Université de Bourgogne ( UB ) -Centre National de la Recherche Scientifique ( CNRS ), CEMAGREF Antony, CEMAGREF, Laboratoire Kastler Brossel ( LKB (Jussieu) ), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris ( FRDPENS ), École normale supérieure - Paris ( ENS Paris ) -Centre National de la Recherche Scientifique ( CNRS ) -École normale supérieure - Paris ( ENS Paris ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Institut d'Electronique et de Télécommunications de Rennes ( IETR ), Université de Nantes ( UN ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National des Sciences Appliquées - Rennes ( INSA Rennes ) -CentraleSupélec-Centre National de la Recherche Scientifique ( CNRS ), Centro de Química Estrutural, Instituto Superior Técnico, Universidade de Lisboa, Lisboa, Département de Physique ( dpuf ), Institut des Nanosciences de Paris ( INSP ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS ), Paul Scherrer Institute ( PSI ), Institut fur Teilchenphysik, Swiss Federal Institute of Technology in Zürich ( ETH Zürich ), Universidade do Porto = University of Porto, Universität Stuttgart [Stuttgart], Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Université de Nantes (UN)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), and Université de Nantes (UN)-Université de Rennes 1 (UR1)
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Physics ,History ,Proton ,[PHYS.PHYS.PHYS-ATOM-PH]Physics [physics]/Physics [physics]/Atomic Physics [physics.atom-ph] ,[ PHYS.PHYS.PHYS-ATOM-PH ] Physics [physics]/Physics [physics]/Atomic Physics [physics.atom-ph] ,Hydrogen atom ,01 natural sciences ,010305 fluids & plasmas ,Computer Science Applications ,Education ,Nuclear physics ,Rydberg constant ,Deuterium ,Charge radius ,0103 physical sciences ,Atom ,Physics::Atomic Physics ,Atomic physics ,010306 general physics ,Hyperfine structure ,Exotic atom - Abstract
We have recently measured the 2S1/2⁼¹ − 2P3/2 ⁼ ² energy splitting in the muonic hydrogen atom μp to be 49881.88 (76) GHz. Using recent QED calculations of the fine-, hyperfine, QED and finite size contributions we obtain a root-mean-square proton charge radius of rp = 0.84184 (67) fm. This value is ten times more precise, but 5 standard deviations smaller, than the 2006 CODATA value of rp = 0.8768 (69) fm. The source of this discrepancy is unknown. Using the precise measurements of the 1S-2S transition in regular hydrogen and deuterium and our value of rp we obtain improved values of the Rydberg constant, R∞ = 10973731.568160 (16) m⁻¹and the rms charge radius of the deuteron rd = 2.12809 (31) fm.
- Published
- 2011
17. Densification and grain growth during solid state sintering of LaPO4
- Author
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Fabienne Audubert, Didier Bernache-Assollant, Damien Bregiroux, Laboratoire de Chimie de la Matière Condensée de Paris (LCMCP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Service Plutonium Uranium et Actinides mineurs (SPUA), Département d'Etudes des Combustibles (DEC), CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-CEA-Direction des Energies (ex-Direction de l'Energie Nucléaire) (CEA-DES (ex-DEN)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre Ingénierie et Santé (CIS-ENSMSE), École des Mines de Saint-Étienne (Mines Saint-Étienne MSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Département Biomécanique et Biomatériaux (DB2M-ENSMSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-CIS, Laboratoire des Procédés en Milieux Granulaires (LPMG-EMSE), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Centre National de la Recherche Scientifique (CNRS), Institut Fédératif de Recherche en Sciences et Ingénierie de la Santé (IFRESIS), Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure des Mines de St Etienne (ENSM ST-ETIENNE)-Centre National de la Recherche Scientifique (CNRS), Université Paris 06, Commissariat à l'Énergie Atomique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Collège de France (CdF (institution))-Institut de Chimie du CNRS (INC), Institut Fédératif de Recherche en Sciences et Ingénierie de la Santé (IFRESIS-ENSMSE), and Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-IFR143
- Subjects
Materials science ,Microstructure-final ,Sintering ,02 engineering and technology ,010402 general chemistry ,01 natural sciences ,Materials Chemistry ,Effective diffusion coefficient ,Grain boundary diffusion coefficient ,[SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering ,Composite material ,[SDV.IB.BIO]Life Sciences [q-bio]/Bioengineering/Biomaterials ,Grain boundary strengthening ,Process Chemistry and Technology ,Metallurgy ,Lattice diffusion coefficient ,021001 nanoscience & nanotechnology ,Grain size ,0104 chemical sciences ,Surfaces, Coatings and Films ,Electronic, Optical and Magnetic Materials ,Grain growth ,Ceramics and Composites ,Grain boundary ,0210 nano-technology - Abstract
International audience; This work is devoted to the kinetic study of densification and grain growth of LaPO4 ceramics. By sintering at a temperature close to 1500 degrees C, densification rate can reach up to 98% of the theoretical density and grain growth can be controlled in the range 0.6-4 mu m. Isothermal shrinkage measurements carried out by dilatometry revealed that densification occurs by lattice diffusion from the grain boundary to the neck. The activation energy for densification (E-D) is evaluated as 480 +/- 4 kJ mol(-1). Grain growth is governed by lattice diffusion controlled pore drag and the activation energy (E-G) is found to be 603 +/- 2 kJ mol(-1). The pore mobility is so low that grain growth only occurs for almost fully dense materials.
- Published
- 2009
18. Multilayered piezoelectric refined plate theory
- Author
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Claire Ossadzow-David, Maurice Touratier, Université Paris 06, Laboratoire de Mécanique des Systèmes et des Procédés (LMSP), Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS), and École Nationale Supérieure des Arts et Métiers (ENSAM)
- Subjects
Force density ,Mathematical analysis ,Constitutive equation ,Aerospace Engineering ,02 engineering and technology ,[SPI.MECA]Engineering Sciences [physics]/Mechanics [physics.med-ph] ,021001 nanoscience & nanotechnology ,Piezoelectricity ,Numerical integration ,Vibration ,020303 mechanical engineering & transports ,Classical mechanics ,0203 mechanical engineering ,Plate theory ,Boundary value problem ,0210 nano-technology ,Statics ,Mathematics - Abstract
A two-dimensional theory for the analysis of multilayered piezoelectric plates is presented. The theory is based on a hybrid approach in which the continuity conditions for both mechanical and electric unknowns at layer interfaces, as well as the imposed conditions on the bounding surfaces and at the interfaces, are independently satisfied. Then, the piezoelectric boundary-value problem is stated using mechanical displacements and electrostatic potential, in conjunction with the coupled piezoelectric constitutive law. The proposed model is simple to use, incorporating only five independent generalized displacements and one or two independent generalized electrostatic potentials as unknowns. The number of electric unknowns depends on the number of layers and electric prescribed conditions. The accuracy of the proposed theory is assessed through investigation of significant problems, for which an exact three-dimensional solution is known from Heyliger: first, in dynamics, the free vibrations of five-layered piezoelectric plates and second, in statics, for three-layered plates with an imposed force density. Results obtained with our model compare very well with the exact three-dimensional theory.
- Published
- 2003
19. NEMO: a tool for analyzing gene and chromosome territory distributions from 3D-FISH experiments
- Author
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Y. Lahbib-Mansais, Joël Gellin, Thomas Boudier, Florence Mompart, Eddie Iannuccelli, Martine Yerle, Laboratoire de Génétique Cellulaire (LGC), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, IFR83, Université Paris 06, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT), Institut de Biologie Intégrative (IFR-BI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
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Statistics and Probability ,Java ,Computer science ,[SDV]Life Sciences [q-bio] ,computer.software_genre ,Biochemistry ,Chromosomes ,World Wide Web ,User-Computer Interface ,03 medical and health sciences ,0302 clinical medicine ,Mode (computer interface) ,Image Processing, Computer-Assisted ,Molecular Biology ,In Situ Hybridization, Fluorescence ,030304 developmental biology ,Graphical user interface ,computer.programming_language ,Cell Nucleus ,0303 health sciences ,business.industry ,computer.file_format ,Computer Science Applications ,Computational Mathematics ,Genes ,Computational Theory and Mathematics ,030220 oncology & carcinogenesis ,Chromosome Territory ,Operating system ,%22">Fish ,The Internet ,Image file formats ,User interface ,business ,computer ,Software - Abstract
Summary: Three-dimensional fluorescence in situ hybridization (3D-FISH) is used to study the organization and the positioning of chromosomes or specific sequences such as genes or RNA in cell nuclei. Many different programs (commercial or free) allow image analysis for 3D-FISH experiments. One of the more efficient open-source programs for automatically processing 3D-FISH microscopy images is Smart 3D-FISH, an ImageJ plug-in designed to automatically analyze distances between genes. One of the drawbacks of Smart 3D-FISH is that it has a rather basic user interface and produces its results in various text and image files thus making the data post-processing step time consuming. We developed a new Smart 3D-FISH graphical user interface, NEMO, which provides all information in the same place so that results can be checked and validated efficiently. NEMO gives users the ability to drive their experiments analysis in either automatic, semi-automatic or manual detection mode. We also tuned Smart 3D-FISH to better analyze chromosome territories. Availability: NEMO is a stand-alone Java application available for Windows and Linux platforms. The program is distributed under the creative commons licence and can be freely downloaded from https://www-lgc.toulouse.inra.fr/nemo Contact: eddie.iannuccelli@toulouse.inra.fr
- Published
- 2010
20. Rydberg atoms in crossed electric and magnetic fields. Experimental evidence for the Pauli quantization
- Author
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F. Penent, D. Delande, F. Biraben, J.C. Gay, Laboratoire de Chimie Physique - Matière et Rayonnement (LCPMR), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Pierre et Marie Curie - Paris 6 (UPMC), Laboratoire Kastler Brossel (LKB (Jussieu)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Paris 06, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Physics ,Zeeman effect ,01 natural sciences ,Atomic and Molecular Physics, and Optics ,010305 fluids & plasmas ,Electronic, Optical and Magnetic Materials ,Magnetic field ,symbols.namesake ,Pauli exclusion principle ,Stark effect ,Electric field ,0103 physical sciences ,Rydberg atom ,symbols ,Rydberg formula ,Physics::Atomic Physics ,[PHYS.PHYS.PHYS-CHEM-PH]Physics [physics]/Physics [physics]/Chemical Physics [physics.chem-ph] ,Electrical and Electronic Engineering ,Physical and Theoretical Chemistry ,Rydberg state ,Atomic physics ,010306 general physics ,ComputingMilieux_MISCELLANEOUS - Abstract
The experimental evidence for the Pauli quantization obeyed by the Rydberg spectrum of rubidium, in crossed electric and magnetic fields, is reported. When the external field perturbation associated with Zeeman and linear Stark effects are of the same order but small compared to the Coulomb binding energy, the energy levels of the system are given by E n,k = -R/n 2 + ɡK (ω 2 L + ω 2 E ) 1 2 , where K is an integer ω L , ω E the Larmor and linear Stark frequencies respectively.
- Published
- 1984
21. Impacts of farmland decontamination on 137 Cs transfers in rivers after Fukushima nuclear accident: Evidence from a retrospective sediment core study.
- Author
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Chalaux-Clergue T, Foucher A, Chaboche PA, Hayashi S, Tsuji H, Wakiyama Y, Huon S, Vandromme R, Cerdan O, Nakao A, and Evrard O
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- Japan, Water Pollutants, Radioactive analysis, Farms, Retrospective Studies, Fukushima Nuclear Accident, Cesium Radioisotopes analysis, Rivers chemistry, Decontamination methods, Radiation Monitoring, Geologic Sediments chemistry, Soil Pollutants, Radioactive analysis
- Abstract
Following the Fukushima Daiichi Nuclear Power Plant disaster in March 2011, the Japanese government initiated an unprecedented decontamination programme to remediate
137 Cs-contaminated soils and allow population return. This programme involved the removal of topsoil under farmland and residential land, and its replacement with "fresh soil" composed of granitic saprolite. However, decontamination was limited to these two land uses, without remediating forests, which cover 70 % of the surface area in the affected region. In this unprecedented context, the specific impact of this unique decontamination programme on137 Cs transfers in river systems remains to be quantified at the catchment scale. In this study, based on the analysis of a sediment core collected in June 2021 in the Mano Dam reservoir draining a decontaminated catchment, the effects of soil decontamination on particle-bound137 Cs dynamics and sediment source contributions in response to a succession of extreme precipitation events were retrospectively assessed. The sequence of sediment layer deposition and its chronology were reconstructed through the analysis of several diagnostic properties (organic matter, elemental geochemistry, visible colourimetry, granulometry) and contextual information. During abandonment (2011-2016), cropland contribution decreased (31 %). Concurrently,137 Cs activity and deposition flux decreased (19 and 29%year-1 , respectively). Following decontamination (2017), sediment transfer increased (270 %) in response to increased contributions from decontaminated cropland and "fresh soil" (625 % and 180 % respectively). Meanwhile, forest contributions remained stable. In contrast,137 Cs activity dropped (65 %), although137 Cs deposition flux remained constant. Forests acted as a stable source of137 Cs. Accordingly,137 Cs deposition flux after decontamination (2016-2021) was similar to that observed during the 5-years period of land abandonment (2011-2016), as a result of the regrowth of spontaneous vegetation over farmland, protecting soil against erosion. Future research should further investigate the impact of longer land abandonment that prevailed in some regions decontaminated lately on the137 Cs fluxes in the rivers., Competing Interests: Declaration of competing interest Olivier Evrard reports financial support was provided by French National Research Agency. Olivier Evrard reports financial support was provided by French Alternative Energies and Atomic Energy Commission (CEA). Olivier Evrard reports financial support was provided by French National Center for Scientific Research (CNRS). Thomas Chalaux-Clergue reports financial support was provided by French Alternative Energies and Atomic Energy Commission. Thomas Chalaux-Clergue reports financial support was provided by Japan Society for the Promotion of Science (JSPS). Olivier Evrard reports financial support was provided by Environmental Radioactivity Research Network Center (ERAN). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)- Published
- 2024
- Full Text
- View/download PDF
22. Integrated Stopped-Flow Device for the Study of Porous Materials Using Hyperpolarized 129 Xe NMR.
- Author
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Li J, Léonce E, Coutellier C, Boutin C, Chighine K, Rivron C, Davidson A, and Berthault P
- Abstract
A simple, low-cost, and efficient device is proposed for the study of porous materials via NMR using small gas probes. Mainly built through additive manufacturing and being equipped with a radiofrequency solenoid microcoil, it only requires tiny quantities of sample and/or gas and is particularly suited for hyperpolarized xenon. The performances of this device have been accessed on a commercial sample of MCM-41 exhibiting multiporosity. Both the delivery mode of hyperpolarized xenon and the stopped-flow system are judged as efficient according to 2D
129 Xe self-diffusion and EXSY experiments.- Published
- 2024
- Full Text
- View/download PDF
23. Bioaccumulation of trace metals in the plastisphere: Awareness of environmental risk from a European perspective.
- Author
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Lenoble V, Cindrić AM, Briand JF, Pedrotti ML, Lacerda AL, Muniategui-Lorenzo S, Fernández-González V, Moscoso-Pérez CM, Andrade-Garda JM, Casotti R, Murano C, Donnarumma V, Frizzi S, Hannon C, Joyce H, Nash R, and Frias J
- Subjects
- Bioaccumulation, Metals, France, Polymers, Environmental Monitoring, Plastics, Water Pollutants, Chemical analysis, Environmental Pollutants, Trace Elements, Metals, Heavy analysis
- Abstract
The term "Plastisphere" refers to the biofilm layer naturally formed by microorganisms attaching to plastic surfaces. This layer possesses the capability to adsorb persistent organic and inorganic pollutants, particularly trace metals, which are the focus of this research study. Immersion experiments were concurrently conducted in five locations spanning four European countries (France, Ireland, Spain, and Italy) utilising eight distinct polymers. These immersions, repeated every three months over a one-year period, aimed to evaluate the baseline bioaccumulation of 12 trace metals. The study underscores the intricate nature of metal bioaccumulation, influenced by both micro-scale factors (such as polymer composition) and macro-scale factors (including geographical site and seasonal variations). Villefranche Bay in France exhibited the lowest metals bioaccumulation, whereas Naples in Italy emerged as the site where bioaccumulation was often the highest for the considered metals. Environmental risk assessment was also conducted in the study. The lightweight nature of certain plastics allows them to be transported across significant distances in the ocean. Consequently, evaluating trace metal concentrations in the plastisphere is imperative for assessing potential environmental repercussions that plastics, along with their associated biota, may exert even in locations distant from their point of emission., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
24. LSD1 controls a nuclear checkpoint in Wnt/β-Catenin signaling to regulate muscle stem cell self-renewal.
- Author
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Mouradian S, Cicciarello D, Lacoste N, Risson V, Berretta F, Le Grand F, Rose N, Simonet T, Schaeffer L, and Scionti I
- Subjects
- Animals, Mice, Cell Nucleus metabolism, Spindle Apparatus metabolism, Cell Differentiation genetics, Humans, Stem Cells metabolism, Stem Cells cytology, Histone Demethylases metabolism, Histone Demethylases genetics, Wnt Signaling Pathway, beta Catenin metabolism, beta Catenin genetics, Cell Self Renewal genetics
- Abstract
The Wnt/β-Catenin pathway plays a key role in cell fate determination during development and in adult tissue regeneration by stem cells. These processes involve profound gene expression and epigenome remodeling and linking Wnt/β-Catenin signaling to chromatin modifications has been a challenge over the past decades. Functional studies of the lysine demethylase LSD1/KDM1A converge to indicate that this epigenetic regulator is a key regulator of cell fate, although the extracellular cues controlling LSD1 action remain largely unknown. Here we show that β-Catenin is a substrate of LSD1. Demethylation by LSD1 prevents β-Catenin degradation thereby maintaining its nuclear levels. Consistently, in absence of LSD1, β-Catenin transcriptional activity is reduced in both MuSCs and ESCs. Moreover, inactivation of LSD1 in mouse muscle stem cells and embryonic stem cells shows that LSD1 promotes mitotic spindle orientation via β-Catenin protein stabilization. Altogether, by inscribing LSD1 and β-Catenin in the same molecular cascade linking extracellular factors to gene expression, our results provide a mechanistic explanation to the similarity of action of canonical Wnt/β-Catenin signaling and LSD1 on stem cell fate., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
- Published
- 2024
- Full Text
- View/download PDF
25. Tardigrades in the marine plastisphere: New hitchhikers surfing plastics.
- Author
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Lacerda AL, Frias J, and Pedrotti ML
- Subjects
- Animals, Plastics, Oceans and Seas, Polypropylenes, Ecosystem, Tardigrada
- Abstract
Tardigrades are remarkable microorganisms known for their extraordinary resilience in diverse environments, including extreme conditions such as outer space. They are known for their interactions with natural substrates in terrestrial and aquatic systems, but have remained largely unexplored in relation to marine plastics. This study aims to investigate the colonization of plastics, ranging from fossil fuel-based to bioplastics, in the coastal zones of four countries (Brazil, Ireland, France and Italy). Here, we report the first documented occurrence of tardigrades colonizing plastic substrates. We identified five amplicon sequence variants (ASVs) belonging to the Tardigrada phylum, specifically in a post-consumer polypropylene, in the coastal zone of Galway, Ireland. This discovery raises questions about the characteristics of different plastics influencing on tardigrades' adhesion. Tardigrades hitchhiking on plastics in the oceans could expand their habitat range, possibly displacing native species and altering trophic interactions, with potential consequences for the overall biodiversity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2024
- Full Text
- View/download PDF
26. Pathogenic DPAGT1 variants in limb-girdle congenital myasthenic syndrome (LG-CMS) associated with tubular aggregates and ORAI1 hypoglycosylation.
- Author
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Brande LV, Bauché S, Pérez-Guàrdia L, Sternberg D, Seferian AM, Malfatti E, Silva-Rojas R, Labasse C, Chevessier F, Carlier P, Eymard B, Romero NB, Laporte J, Servais L, Gidaro T, and Böhm J
- Abstract
Aims: Limb-girdle congenital myasthenic syndrome (LG-CMS) is a genetically heterogeneous disorder characterized by muscle weakness and fatigability. The LG-CMS gene DPAGT1 codes for an essential enzyme of the glycosylation pathway, a posttranslational modification mechanism shaping the structure and function of proteins. In DPAGT1-related LG-CMS, reduced glycosylation of the acetylcholine receptor (AChR) reduces its localization at the neuromuscular junction (NMJ), and results in diminished neuromuscular transmission. LG-CMS patients also show tubular aggregates on muscle biopsy, but the origin and potential contribution of the aggregates to disease development are not understood. Here, we describe two LG-CMS patients with the aim of providing a molecular diagnosis and to shed light on the pathways implicated in tubular aggregate formation., Methods: Following clinical examination of the patients, we performed next-generation sequencing (NGS) to identify the genetic causes, analysed the biopsies at the histological and ultrastructural levels, investigated the composition of the tubular aggregates, and performed experiments on protein glycosylation., Results: We identified novel pathogenic DPAGT1 variants in both patients, and pyridostigmine treatment quantitatively improved muscle force and function. The tubular aggregates contained proteins of the sarcoplasmic reticulum (SR) and structurally conformed to the aggregates observed in tubular aggregate myopathy (TAM). TAM arises from overactivation of the plasma membrane calcium channel ORAI1, and functional studies on muscle extracts from our LG-CMS patients evidenced abnormal ORAI1 glycosylation., Conclusions: We expand the genetic variant spectrum of LG-CMS and provide a genotype/phenotype correlation for pathogenic DPAGT1 variants. The discovery of ORAI1 hypoglycosylation in our patients highlights a physiopathological link between LG-CMS and TAM., (This article is protected by copyright. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
27. Molecular Analysis of a Congenital Myasthenic Syndrome Due to a Pathogenic Variant Affecting the C-Terminus of ColQ.
- Author
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Barbeau S, Semprez F, Dobbertin A, Merriadec L, Roussange F, Eymard B, Sternberg D, Fournier E, Karasoy H, Martinat C, and Legay C
- Subjects
- Male, Humans, Animals, Mice, Adult, Acetylcholinesterase genetics, Acetylcholinesterase metabolism, Neuromuscular Junction metabolism, Receptors, Cholinergic metabolism, Collagen metabolism, Mutation, Myasthenic Syndromes, Congenital genetics, Myasthenic Syndromes, Congenital metabolism
- Abstract
Congenital Myasthenic Syndromes (CMSs) are rare inherited diseases of the neuromuscular junction characterized by muscle weakness. CMSs with acetylcholinesterase deficiency are due to pathogenic variants in COLQ, a collagen that anchors the enzyme at the synapse. The two COLQ N-terminal domains have been characterized as being biochemical and functional. They are responsible for the structure of the protein in the triple helix and the association of COLQ with acetylcholinesterase. To deepen the analysis of the distal C-terminal peptide properties and understand the CMSs associated to pathogenic variants in this domain, we have analyzed the case of a 32 year old male patient bearing a homozygote splice site variant c.1281 C > T that changes the sequence of the last 28 aa in COLQ. Using COS cell and mouse muscle cell expression, we show that the COLQ variant does not impair the formation of the collagen triple helix in these cells, nor its association with acetylcholinesterase, and that the hetero-oligomers are secreted. However, the interaction of COLQ variant with LRP4, a signaling hub at the neuromuscular junction, is decreased by 44% as demonstrated by in vitro biochemical methods. In addition, an increase in all acetylcholine receptor subunit mRNA levels is observed in muscle cells derived from the patient iPSC. All these approaches point to pathophysiological mechanisms essentially characterized by a decrease in signaling and the presence of immature acetylcholine receptors.
- Published
- 2023
- Full Text
- View/download PDF
28. Rationale and design of the ARAMIS trial: Anakinra versus placebo, a double blind randomized controlled trial for the treatment of acute myocarditis.
- Author
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Kerneis M, Cohen F, Combes A, Amoura Z, Pare C, Brugier D, Puymirat E, Abtan J, Lattuca B, Dillinger JG, Hauguel-Moreau M, Silvain J, Salem JE, Gandjbakhch E, Hekimian G, Redheuil A, Vicaut E, and Montalescot G
- Abstract
Background: Acute myocarditis is an inflammation of the myocardium that can cause life-threatening events. However, anti-inflammatory strategies did not reduce the risk of clinical outcomes in randomized trials. Recently, experimental studies have suggested that specific blockade of the interleukin-1β immune innate pathway could be effective in acute myocarditis., Aim: To test the hypothesis that inhibition of the interleukin-1β immune innate pathway can reduce the risk of clinical events in acute myocarditis., Methods: The "Anakinra versus placebo double blind Randomized controlled trial for the treatment of Acute MyocarditIS" (ARAMIS) trial (ClinicalTrials.gov identifier: NCT03018834) is a national multicentre randomized parallel-group double blind study among symptomatic patients with elevated cardiac troponin and cardiac magnetic resonance-proven acute myocarditis. Patients (n=120) are randomized within 72hours of hospital admission to receive a daily subcutaneous dose of anakinra 100mg or placebo during the hospitalization, in addition to standard of care, including an angiotensin-converting enzyme inhibitor and a beta-blocker. The primary endpoint is the number of days alive free from any myocarditis complication, including ventricular arrhythmias, heart failure, recurrent chest pain requiring medication and ventricular dysfunction (defined as left ventricular ejection fraction<50%), from randomization to 28 days after hospital discharge. At 28 days after discharge, patients with normal left ventricular ejection fraction are then randomized to angiotensin-converting enzyme inhibitor continuation or discontinuation and all patients are followed for 1 year, with regular left ventricular function evaluation., Conclusions: ARAMIS is the first trial evaluating inhibition of the interleukin-1β immune innate pathway in the setting of acute myocarditis. Although of small size, it will be the largest randomized trial in acute myocarditis, a serious and poorly studied cardiac condition., (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)
- Published
- 2023
- Full Text
- View/download PDF
29. Multivalent Dynamic Colocalization of Avian Influenza Polymerase and Nucleoprotein by Intrinsically Disordered ANP32A Reveals the Molecular Basis of Human Adaptation.
- Author
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Camacho-Zarco AR, Yu L, Krischuns T, Dedeoglu S, Maurin D, Bouvignies G, Crépin T, Ruigrok RWH, Cusack S, Naffakh N, and Blackledge M
- Subjects
- Animals, Humans, Nucleotidyltransferases, Amino Acids, Mutation, Probability, Mammals, Nuclear Proteins, RNA-Binding Proteins genetics, Influenza in Birds
- Abstract
Adaptation of avian influenza RNA polymerase (FluPol) to human cells requires mutations on the 627-NLS domains of the PB2 subunit. The E627K adaptive mutation compensates a 33-amino-acid deletion in the acidic intrinsically disordered domain of the host transcription regulator ANP32A, a deletion that restricts FluPol activity in mammalian cells. The function of ANP32A in the replication transcription complex and in particular its role in host restriction remains poorly understood. Here we characterize ternary complexes formed between ANP32A, FluPol, and the viral nucleoprotein, NP, supporting the putative role of ANP32A in shuttling NP to the replicase complex. We demonstrate that while FluPol and NP can simultaneously bind distinct linear motifs on avian ANP32A, the deletion in the shorter human ANP32A blocks this mode of colocalization. NMR reveals that NP and human-adapted FluPol, containing the E627 K mutation, simultaneously bind the identical extended linear motif on human ANP32A in an electrostatically driven, highly dynamic and multivalent ternary complex. This study reveals a probable molecular mechanism underlying host adaptation, whereby E627K, which enhances the basic surface of the 627 domain, is selected to confer the necessary multivalent properties to allow ANP32A to colocalize NP and FluPol in human cells.
- Published
- 2023
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30. Virus-Host Interactions Drive Contrasting Bacterial Diel Dynamics in the Ocean.
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Chen X, Hu C, Wei W, Yang Y, Weinbauer MG, Li H, Ren S, Ma R, Huang Y, Luo T, Jiao N, and Zhang R
- Abstract
Marine organisms perform a sea of diel rhythmicity. Planktonic diel dynamics have been shown to be driven by light, energy resources, circadian rhythms, and the coordinated coupling of photoautotrophs and heterotrophic bacterioplankton. Here, we explore the diel fluctuation of viral production and decay and their impact on the total and active bacterial community in the coastal and open seawaters of the South China Sea. The results showed that the night-production diel pattern of lytic viral production was concurrent with the lower viral decay at night, contributing to the accumulation of the viral population size during the night for surface waters. The diel variations in bacterial activity, community composition, and diversity were found highly affected by viral dynamics. This was revealed by the finding that bacterial community diversity was positively correlated to lytic viral production in the euphotic zone of the open ocean but was negatively related to lysogenic viral production in the coastal ocean. Such distinct but contrasting correlations suggest that viral life strategies can not only contribute to diversifying bacterial community but also potentially piggyback their host to dominate bacterial community, suggesting the tightly synchronized depth-dependent and habitat-specific diel patterns of virus-host interactions. It further implies that viruses serve as an ecologically important driver of bacterial diel dynamics across the ocean, highlighting the viral roles in bacterial ecological and biogeochemical processes in the ocean., (Copyright © 2023 Xiaowei Chen et al.)
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- 2023
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31. Is Zooplankton an Entry Point of Microplastics into the Marine Food Web?
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Gunaalan K, Nielsen TG, Rodríguez Torres R, Lorenz C, Vianello A, Andersen CA, Vollertsen J, and Almeda R
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- Animals, Copepoda, Denmark, Feces chemistry, Environmental Monitoring, Food Chain, Microplastics analysis, Water Pollutants, Chemical analysis, Zooplankton
- Abstract
Microplastics (MPs) overlap in size with phytoplankton and can be ingested by zooplankton, transferring them to higher trophic levels. Copepods are the most abundant metazoans among zooplankton and the main link between primary producers and higher trophic levels. Ingestion of MPs has been investigated in the laboratory, but we still know little about the ingestion of MPs by zooplankton in the natural environment. In this study, we determined the concentration and characteristics of MPs down to 10 μm in zooplankton samples, sorted calanoid copepods, and fecal pellets collected in the Kattegat/Skagerrak Sea (Denmark). We found a median concentration of 1.7 × 10
-3 MPs ind-1 in the zooplankton samples, 2.9 × 10-3 MPs ind-1 in the sorted-copepods, and 3 × 10-3 MPs per fecal pellet. Most MPs in the zooplankton samples and fecal pellets were fragments smaller than 100 μm, whereas fibers dominated in the sorted copepods. Based on the collected data, we estimated a MP budget for the surface layer (0-18 m), where copepods contained only 3% of the MPs in the water, while 5% of the MPs were packed in fecal pellets. However, the number of MPs exported daily to the pycnocline via fecal pellets was estimated to be 1.4% of the total MPs in the surface layer. Our results indicate that zooplankton are an entry point of small MPs in the food web, but the number of MPs in zooplankton and their fecal pellets was low compared with the number of MPs found in the water column and the occurrence and/or ingestion of MPs reported for nekton. This suggests a low risk of MP transferring to higher trophic levels through zooplankton and a quantitatively low, but ecologically relevant, contribution of fecal pellets to the vertical exportation of MPs in the ocean.- Published
- 2023
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32. Circulating tumour DNA at baseline for individualised prognostication in patients with chemotherapy-naïve metastatic colorectal cancer. An AGEO prospective study.
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Bachet JB, Laurent-Puig P, Meurisse A, Bouché O, Mas L, Taly V, Cohen R, Gornet JM, Artru P, Louafi S, Thirot-Bidault A, Baumgaertner I, Coriat R, Tougeron D, Lecomte T, Mary F, Aparicio T, Marthey L, Blons H, Vernerey D, and Taieb J
- Subjects
- Humans, Biomarkers, Tumor genetics, Mutation, Prognosis, Prospective Studies, Circulating Tumor DNA, Colonic Neoplasms, Colorectal Neoplasms drug therapy, Colorectal Neoplasms genetics, Colorectal Neoplasms pathology, Rectal Neoplasms
- Abstract
Purpose: Baseline circulating tumour DNA (ctDNA) is a potential prognostic marker in metastatic colorectal cancer (mCRC) patients. However, few studies have compared ctDNA with the usual prognostic factors, and no ctDNA cut-off has been proposed for daily use in clinical practice., Patients and Methods: Chemotherapy-naive patients with mCRC were prospectively included. Plasma samples were collected at diagnosis and analysed centrally by both NGS and methylation digital PCR. Baseline patient and disease characteristics, treatment regimens, and secondary surgeries were collected. The restricted cubic spline method was used to define the optimal cut-off of ctDNA mutated allelic frequency (MAF). Prognostic values were assessed on overall survival (OS) using Cox models., Results: From July 2015 to December 2016, 412 patients were included. ctDNA was undetectable in 83 patients (20%). ctDNA was an independent prognostic marker for OS considering the whole study population. The optimal cut-off for ctDNA MAF was 20% with median OS of 16.0 and 35.8 months for patients with MAF ≥20% and<20%, respectively (hazard ratio = 0.40; 95% confidence intervals: 0.31-0.51; P < 0.0001). The independent prognostic value of ctDNA MAF at 20% was confirmed in subgroups defined by RAS/BRAF status or resectability of metastases. Combining ctDNA MAF and carcinoembryonic antigen levels allowed us to define three different prognostic groups with median OS of 14.2, 21.1, and 46.4 months (P < 0.0001)., Conclusion: ctDNA with a MAF cut-off of 20% improves prognostication of chemotherapy-naïve mCRC patients and may be useful in the future for individualised therapeutic decisions and as a stratification factor in clinical trials., Trial Registration: Clinicaltrials.gov, NCT02502656., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: J.B. Bachet has received personal fees from Amgen, Bayer, Bristol Myers Squibb, Merck Serono, Merck Sharp & Dohme, Pierre Fabre, Sanofi, Servier, and non-financial support from Amgen, Merck Serono, and Roche, outside the submitted work. P. Laurent-Puig has received grants from AGEO during the conduct of the study; personal fees from Amgen, Biocartis, Merck Serono, Astrazeneca, Sanofi, Pierre Fabre, MSD, outside the submitted work. O. Bouché has received personal fees from Merck Serono, Amgen, Bayer, Apmomia Therapeutics, MSD, Servier and Pierre Fabre, outside the submitted work. V. Taly has received honoraria from Raindance Technologies during the conduct of the study, and honoraria from Boehringer Ingelheim, outside the submitted work. P. Artru has received personal fees from Merck Serono during the conduct of the study; personal fees from Roche, Sanofi, Celgene, Sanofi, outside the submitted work. D. Tougeron has received personal fees from Amgen, MSD, BMS, Merck Serono, Pierre Fabre, Servier, Sirtex, Ipsen, Roche, outside the submitted work. T. Lecomte has received personnel fees from Amgen, Merck Serono, Sanofi, Ipsen, Bayer, Pierre Fabre and Servier, outside the submitted work. F. Mary has received personal fees from Bayer, Amgen, Merck Serono and Ipsen, outside the submitted work. T. Aparicio has received personal fees from Bristol Myers Squibb, Pierre Fabre, Servier, Amgen, Merck Sharp & Dohme, Sirtex, outside the submitted work. L. Marthey has received personal fees from Roche, personal fees and non-financial support from Takeda, non-financial support from Amgen and Novartis, outside the submitted work. H. Blons has received personal fees from Astra-Zeneca, Merck Serono, Amgen, Boehringer Ingelheim and Pfizer, outside the submitted work. D. Vernerey has received personal fees from HalioDx, outside the submitted work. J. Taieb has received honoraria for speaker or advisory role from BMS, Roche, Merck Serono, Amgen, Servier, Pierre Fabre, Astra Zeneca and MSD, outside the submitted work. A. Meurisse, L. Mas, J.M. Gornet, R. Cohen, S. Louafi, A.Thirot-Bidault, I. Baumgaertner, R. Coriat declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)
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- 2023
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33. Epigenomic mapping identifies an enhancer repertoire that regulates cell identity in bladder cancer through distinct transcription factor networks.
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Neyret-Kahn H, Fontugne J, Meng XY, Groeneveld CS, Cabel L, Ye T, Guyon E, Krucker C, Dufour F, Chapeaublanc E, Rapinat A, Jeffery D, Tanguy L, Dixon V, Neuzillet Y, Lebret T, Gentien D, Davidson I, Allory Y, Bernard-Pierrot I, and Radvanyi F
- Subjects
- Humans, Epigenomics, Epigenesis, Genetic, Gene Expression Regulation, Enhancer Elements, Genetic genetics, Transcription Factors genetics, Transcription Factors metabolism, Urinary Bladder Neoplasms pathology
- Abstract
Muscle-invasive bladder cancer (BLCA) is an aggressive disease. Consensus BLCA transcriptomic subtypes have been proposed, with two major Luminal and Basal subgroups, presenting distinct molecular and clinical characteristics. However, how these distinct subtypes are regulated remains unclear. We hypothesized that epigenetic activation of distinct super-enhancers could drive the transcriptional programs of BLCA subtypes. Through integrated RNA-sequencing and epigenomic profiling of histone marks in primary tumours, cancer cell lines, and normal human urothelia, we established the first integrated epigenetic map of BLCA and demonstrated the link between subtype and epigenetic control. We identified the repertoire of activated super-enhancers and highlighted Basal, Luminal and Normal-associated SEs. We revealed super-enhancer-regulated networks of candidate master transcription factors for Luminal and Basal subgroups including FOXA1 and ZBED2, respectively. FOXA1 CRISPR-Cas9 mutation triggered a shift from Luminal to Basal phenotype, confirming its role in Luminal identity regulation and induced ZBED2 overexpression. In parallel, we showed that both FOXA1 and ZBED2 play concordant roles in preventing inflammatory response in cancer cells through STAT2 inhibition. Our study furthers the understanding of epigenetic regulation of muscle-invasive BLCA and identifies a co-regulated network of super-enhancers and associated transcription factors providing potential targets for the treatment of this aggressive disease., (© 2023. The Author(s).)
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- 2023
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34. Effect of flow change on brain injury during an experimental model of differential hypoxaemia in cardiogenic shock supported by extracorporeal membrane oxygenation.
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Rozencwajg S, Heinsar S, Wildi K, Jung JS, Colombo SM, Palmieri C, Sato K, Ainola C, Wang X, Abbate G, Sato N, Dyer WB, Livingstone S, Helms L, Bartnikowski N, Bouquet M, Passmore MR, Hyslop K, Vidal B, Reid JD, McGuire D, Wilson ES, Rätsep I, Lorusso R, Schmidt M, Suen JY, Bassi GL, and Fraser JF
- Subjects
- Animals, Hypoxia complications, Models, Theoretical, Sheep, Shock, Cardiogenic etiology, Brain Injuries complications, Extracorporeal Membrane Oxygenation adverse effects
- Abstract
Differential hypoxaemia (DH) is common in patients supported by femoral veno-arterial extracorporeal membrane oxygenation (V-A ECMO) and can cause cerebral hypoxaemia. To date, no models have studied the direct impact of flow on cerebral damage. We investigated the impact of V-A ECMO flow on brain injury in an ovine model of DH. After inducing severe cardiorespiratory failure and providing ECMO support, we randomised six sheep into two groups: low flow (LF) in which ECMO was set at 2.5 L min
-1 ensuring that the brain was entirely perfused by the native heart and lungs, and high flow (HF) in which ECMO was set at 4.5 L min-1 ensuring that the brain was at least partially perfused by ECMO. We used invasive (oxygenation tension-PbTO2 , and cerebral microdialysis) and non-invasive (near infrared spectroscopy-NIRS) neuromonitoring, and euthanised animals after five hours for histological analysis. Cerebral oxygenation was significantly improved in the HF group as shown by higher PbTO2 levels (+ 215% vs - 58%, p = 0.043) and NIRS (67 ± 5% vs 49 ± 4%, p = 0.003). The HF group showed significantly less severe brain injury than the LF group in terms of neuronal shrinkage, congestion and perivascular oedema (p < 0.0001). Cerebral microdialysis values in the LF group all reached the pathological thresholds, even though no statistical difference was found between the two groups. Differential hypoxaemia can lead to cerebral damage after only a few hours and mandates a thorough neuromonitoring of patients. An increase in ECMO flow was an effective strategy to reduce such damages., (© 2023. The Author(s).)- Published
- 2023
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35. The smallest in the deepest: the enigmatic role of viruses in the deep biosphere.
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Cai L, Weinbauer MG, Xie L, and Zhang R
- Abstract
It is commonly recognized that viruses control the composition, metabolism, and evolutionary trajectories of prokaryotic communities, with resulting vital feedback on ecosystem functioning and nutrient cycling in a wide range of ecosystems. Although the deep biosphere has been estimated to be the largest reservoir for viruses and their prokaryotic hosts, the biology and ecology of viruses therein remain poorly understood. The deep virosphere is an enigmatic field of study in which many critical questions are still to be answered. Is the deep virosphere simply a repository for deeply preserved, non-functioning virus particles? Or are deep viruses infectious agents that can readily infect suitable hosts and subsequently shape microbial populations and nutrient cycling? Can the cellular content released by viral lysis, and even the organic structures of virions themselves, serve as the source of bioavailable nutrients for microbial activity in the deep biosphere as in other ecosystems? In this review, we synthesize our current knowledge of viruses in the deep biosphere and seek to identify topics with the potential for substantial discoveries in the future., Competing Interests: None declared., (© The Author(s) 2023. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)
- Published
- 2023
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36. FGFR3 Mutational Activation Can Induce Luminal-like Papillary Bladder Tumor Formation and Favors a Male Sex Bias.
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Shi MJ, Fontugne J, Moreno-Vega A, Meng XY, Groeneveld C, Dufour F, Kamoun A, Viborg Lindskrog S, Cabel L, Krucker C, Rapinat A, Dunois-Larde C, Lepage ML, Chapeaublanc E, Levrel O, Dixon V, Lebret T, Almeida A, De Reynies A, Rochel N, Dyrskjøt L, Allory Y, Radvanyi F, and Bernard-Pierrot I
- Subjects
- Female, Humans, Male, Mice, Animals, Urinary Bladder pathology, Sexism, Mutation, Mice, Transgenic, Androgens adverse effects, Receptor, Fibroblast Growth Factor, Type 3 genetics, Urinary Bladder Neoplasms pathology
- Abstract
Background: Bladder cancer (BCa) is more common in men and presents differences in molecular subtypes based on sex. Fibroblast growth factor receptor 3 (FGFR3) mutations are enriched in the luminal papillary muscle-invasive BCa (MIBC) and non-MIBC subtypes., Objective: To determine whether FGFR3 mutations initiate BCa and impact BCa male sex bias., Design, Setting, and Participants: We developed a transgenic mouse model expressing the most frequent FGFR3 mutation, FGFR3-S249C, in urothelial cells. Bladder tumorigenesis was monitored in transgenic mice, with and without carcinogen exposure. Mouse and human BCa transcriptomic data were compared., Intervention: Mutant FGFR3 overexpression in mouse urothelium and siRNA knockdown in cell lines, and N-butyl-N(4-hydroxybutyl)-nitrosamine (BBN) exposure., Outcome Measurements and Statistical Analysis: Impact of transgene dosage on tumor frequency, synergy with BBN treatment, and FGFR3 pathway activation were analyzed. The sex-specific incidence of FGFR3-mutated tumors was evaluated in mice and humans. FGFR3 expression in FGFR3-S249C mouse urothelium and in various human epithelia was measured. Mutant FGFR3 regulation of androgen (AR) and estrogen (ESR1) receptor activity was evaluated, through target gene expression (regulon) and reporter assays., Results and Limitations: FGFR3-S249C expression in mice induced low-grade papillary BCa resembling human luminal counterpart at histological, genomic, and transcriptomic levels, and promoted BBN-induced basal BCa formation. Mutant FGFR3 expression levels impacted tumor incidence in mice, and mutant FGFR3-driven human tumors were restricted to epithelia presenting high normal FGFR3 expression levels. BCa male sex bias, also found in our model, was even higher in human FGFR3-mutated tumors compared with wild-type tumors and was associated with higher AR and lower ESR1 regulon activity. Mutant FGFR3 expression inhibited both ESR1 and AR activity in mouse tumors and human cell lines, demonstrating causation only between FGFR3 activation and low ESR1 activity in tumors., Conclusions: Mutant FGFR3 initiates luminal papillary BCa formation and favors BCa male sex bias, potentially through FGFR3-dependent ESR1 downregulation. Patients with premalignant lesions or early-stage BCa could thus potentially benefit from FGFR3 targeting. FGFR3 expression level in epithelia could account for FGFR3-driven carcinoma tissue specificity., Patient Summary: By developing a transgenic mouse model, we showed that gain-of-function mutations of FGFR3 receptor, among the most frequent genetic alterations in bladder cancer (BCa), initiate BCa formation. Our results could support noninvasive detection of FGFR3 mutations and FGFR3 targeting in early-stage bladder lesions., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)
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- 2023
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37. Brain dysfunction in gait disorders of Caribbean atypical Parkinsonism and progressive supranuclear palsy patients: A comparative study.
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Welter ML, Vasseur A, Edragas R, Chaumont H, Pineau F, Mangone G, Olivier C, Leber I, Rivaud-Pechoux S, Lehericy S, Gallea C, Yahia-Cherif L, and Lannuzel A
- Subjects
- Humans, Brain, Caribbean Region, Gait, Supranuclear Palsy, Progressive pathology, Parkinsonian Disorders diagnostic imaging
- Abstract
Introduction: Gait disorders and falls occur early in progressive supranuclear palsy (PSP-RS) and Caribbean atypical parkinsonism (Caribbean AP). However, the link between these signs and brain lesions has never been explored in these patient populations. Here, we investigate and compare the imaging factors that relate to gait and balance disorders in Caribbean AP and PSP-RS patients., Methods: We assessed gait and balance using clinical scales and gait recordings in 16 Caribbean AP and 15 PSP-RS patients and 17 age-matched controls. We measured the grey and white matter brain volumes on 3 T brain MRI images. We performed a principal component analysis (PCA) including all the data to determine differences and similarities between groups, and explore the relationship between gait disorders and brain volumes., Results: Both Caribbean AP patients and PSP-RS have marked gait and balance disorders with similar severity. In both groups, gait and balance disorders were found to be most strongly related to structural changes in the lateral cerebellum, caudate nucleus, and fronto-parietal areas. In Caribbean AP patients, gait disorders were also related to additional changes in the cortex, including frontal, insular, temporal and cuneus lobes, whereas in PSP-RS patients, additional white matter changes involved the mesencephalon and parahippocampal gyrus., Conclusion: Gait and balance disorders in Caribbean AP patients are mainly related to dysfunction of cortical brain areas involved in visuo-sensorimotor processing and self-awareness, whereas these signs mainly result from premotor-brainstem-cerebellar network dysfunction in PSP-RS patients, brain areas involved in initiation and maintenance of locomotor pattern and postural adaptation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2023
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38. Concerted and sequential three-body fragmentation of deep-core-ionized carbon disulfide.
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Guillemin R, Marin T, Zmerli M, Bomme C, Ismail I, Journel L, Marchenko T, Travnikova O, Piancastelli MN, and Simon M
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- Sulfur, Carbon Disulfide
- Abstract
Momentum vector correlation is a powerful tool to study molecular dissociation. We have studied the three-body fragmentation of carbon disulfide after sulfur 1s photoionization by means of momentum imaging techniques. Concerted and sequential pathways are disentangled in three-body fragmentation using adapted analysis strategies. In particular, we introduce various data visualization schemes that are proved to be particularly efficient to determine dissociation dynamics.
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- 2022
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39. Sleep Traits, Night Shift Work and Lung Cancer Risk among Women: Results from a Population-Based Case-Control Study in France (The WELCA Study).
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Cordina-Duverger E, Uchai S, Tvardik N, Billmann R, Martin D, Trédaniel J, Wislez M, Blons H, Laurent-Puig P, Antoine M, Guénel P, Radoï L, and Welca Study Group
- Subjects
- Male, Female, Humans, Work Schedule Tolerance, Case-Control Studies, Sleep, Circadian Rhythm, Logistic Models, Lung, Shift Work Schedule adverse effects, Sleep Wake Disorders, Lung Neoplasms epidemiology, Lung Neoplasms etiology
- Abstract
Circadian rhythm disruption due to night shift work and/or sleep disorders is associated with negative health outcomes including cancer. There is only scant evidence of an association with lung cancer, unlike breast and prostate cancer. We explore the role of sleep disorders and night shift work in lung cancer risk among women in a population-based case-control study, including 716 lung cancer cases and 758 controls. Multivariable logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) associated with sleep duration per day (<7 h, 7−7.9 h, ≥8 h), a summary index of sleep disorders, chronotype, and night shift work exposure metrics. When compared to women with an average sleep duration of 7−7.9 h per day, the OR was 1.39 (95% CI 1.04−1.86) in long sleepers (≥8 h) and 1.16 (95% CI 0.86−1.56) in short sleepers (<7 h). Overall, lung cancer was not associated with the sleep disorder index, nor with night shift work, regardless of the duration of night work or the frequency of night shifts. However, elevated OR associated with the sleep disorder index were found in the subgroup of current smokers. The U-shaped association of lung cancer with sleep duration was more particularly pronounced among women who worked at night ≥5 years. Our findings suggested that sleep patterns are associated with lung cancer risk in women with a potential modifying effect by night shift work duration or tobacco smoking.
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- 2022
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40. Vibrio spp and other potential pathogenic bacteria associated to microfibers in the North-Western Mediterranean Sea.
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Pedrotti ML, de Figueiredo Lacerda AL, Petit S, Ghiglione JF, and Gorsky G
- Subjects
- Animals, Humans, Mediterranean Sea, Bacteria genetics, Dietary Fiber, Racial Groups, Vibrio parahaemolyticus genetics, Gammaproteobacteria
- Abstract
Microfibers, whether synthetic or natural, have increased dramatically in the environment, becoming the most common type of particles in the ocean, and exposing aquatic organisms to multiple negative impacts. Using an approach combining morphology (scanning electron microscopy-SEM) and molecular taxonomy (High-Throughput DNA Sequencing- HTS), we investigated the bacterial composition from floating microfibers (MFs) collected in the northwestern Mediterranean Sea. The average number of bacteria in 100 μm2 on the surface of a fiber is 8 ± 5.9 cells; by extrapolating it to a whole fiber, this represents 2663 ± 1981 bacteria/fiber. Attached bacterial communities were dominated by Alteromonadales, Rhodobacterales, and Vibrionales, including the potentially human/animal pathogen Vibrio parahaemolyticus. This study reveals a high rate of bacterial colonization on MFs, and shows that these particles can host numerous bacterial species, including putative pathogens. Even if we cannot confirm its pathogenicity based only on the taxonomy, this is the first description of such pathogenic Vibrio living attached to MFs in the Mediterranean Sea. The identification of MFs colonizers is valuable in assessing health risks, as their presence can be a threat to bathing and seafood consumption. Considering that MFs can serve as vector for potentially pathogenic microorganisms and other pollutants throughout the ocean, this type of pollution can have both ecological and economic consequences., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Pedrotti et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2022
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41. Nuclear transport and subcellular localization of the dystrophin Dp71 and Dp40 isoforms in the PC12 cell line.
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Sánchez A, Aragón J, Ceja V, Rendon A, and Montanez C
- Subjects
- Active Transport, Cell Nucleus, Animals, Intracellular Space, Karyopherins metabolism, PC12 Cells, Protein Isoforms genetics, Protein Isoforms metabolism, RNA, Messenger metabolism, Rats, Dystrophin genetics, Dystrophin metabolism, beta Karyopherins metabolism
- Abstract
The shortest dystrophins, Dp71 and Dp40, are transcribed from the DMD gene through an internal promoter located in intron 62. These proteins are the main product of the DMD gene in the nervous system and have been involved in various functions related to cellular differentiation and proliferation as well as other cellular processes. Dp71 mRNA undergoes alternative splicing that results in different Dp71 protein isoforms. The subcellular localization of some of these isoforms in the PC12 cell line has been previously reported, and a differential subcellular distribution was observed, which suggests a particular role for each isoform. With the aim of obtaining information on their function, this study identified factors involved in the nuclear transport of Dp71 and Dp40 isoforms in the PC12 cell line. Cell cultures were treated with specific nuclear import/export inhibitors to determine the Dp71 isoform transport routes. The results showed that all isoforms of Dp71 and Dp40 included in the analysis have the ability to enter the cell nucleus through α/β importin, and the main route of nuclear export for Dp71 isoforms is through the exportin CRM1, which is not the case for Dp40., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Inc. All rights reserved.)
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- 2022
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42. [Monkeypox virus infection].
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Cacoub P and Halfon P
- Subjects
- Humans, Monkeypox virus genetics, Mpox (monkeypox) diagnosis, Mpox (monkeypox) epidemiology
- Published
- 2022
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43. Growth of home respiratory equipment from 2006 to 2019 and cost control by health policies.
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Ribeiro Baptista B, Baptiste A, Granger B, Villemain A, Ohayon R, Rabec C, Chabot F, and Gonzalez-Bermejo J
- Subjects
- Humans, Oxygen, Cost Control, Health Policy, Respiratory Insufficiency epidemiology, Respiratory Insufficiency therapy, Noninvasive Ventilation methods
- Abstract
Background: Home respiratory equipment (HRE) designed for the management of chronic respiratory failure includes oxygen therapy (O
2 ), noninvasive ventilation (NIV) and mechanical insufflation-exsufflation (MI-E). The growth of the number of patients treated by HRE, the prevalence and the associated costs in France have not been determined., Methods: The French open access national health insurance aggregated data was used to estimate the evolution of theses parameters from 2006 to 2019., Results: The number of patients treated by HRE increased by 117% between 2006 and 2019, reaching a total of 245,896 patients (367/100,000). Prescriptions for O2 , NIV, and MI-E increased by 88%, 189% and 162%, respectively. In 2019, 139,323 patients received long-term home O2 alone (208/100,000) with a 13% decrease for liquid O2 compared to a 44% increase for O2 concentrator. The number of patients treated by portable oxygen concentrator increased by 509% over the last 5 years. In 2019, 96,126 patients received NIV (144/100,000) and 97% of these patients were treated by NIV for less than 12 h/day. A total of 9,158 patients were treated by MI-E in 2019 (13.6/100,000). Despite the global increase in the number of patients, health costs decreased from 9% to 8% of total medical device spending in 2019 due to adjustment of health policies, such as a reduction of reimbursement rates., Conclusion: Our results highlighted the high rate of HRE prescription, but with cost control as a result of adapted health policies., Competing Interests: Declaration of Competing Interest BRB, AB, BG, AV, RO, CR, FC have no competing interests to declare that are relevant to the content of this article. JG reports receiving grants Breas, Air Liquide, L3 medical and lecture fees from Breas and Resmed. No funding was received for conducting this study., (Copyright © 2022 SPLF and Elsevier Masson SAS. All rights reserved.)- Published
- 2022
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44. The concept of tissue regeneration: Epistemological and historical enquiry from early ideas on the regeneration of bone to the microscopic observations of the regeneration of peripheral nerves.
- Author
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Barbara JG
- Abstract
This paper examines the epistemological history of physiological tissue regeneration theories from Antiquity to the present time focusing on early clinical observations, microscopic investigations of the 19th C. and molecular aspects of the regeneration of peripheral nerves. We aim to show underlying theoretical implications at stake over centuries, with an extreme diversity of local contexts, while slowly emerging ideas were progressively built in the framework of cell theory and that of molecular biology. The overall epistemological lesson is that this long history is far from finished and requires novel experiments and perspectives, as well as the careful inspection of its rich past, as a true scientific tradition, in order to better understand what is nervous regeneration and how we can use it in medicine., Competing Interests: The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Barbara.)
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- 2022
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45. Severe congenital myasthenic syndromes caused by agrin mutations affecting secretion by motoneurons.
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Jacquier A, Risson V, Simonet T, Roussange F, Lacoste N, Ribault S, Carras J, Theuriet J, Girard E, Grosjean I, Le Goff L, Kröger S, Meltoranta J, Bauché S, Sternberg D, Fournier E, Kostera-Pruszczyk A, O'Connor E, Eymard B, Lochmüller H, Martinat C, and Schaeffer L
- Subjects
- Humans, Motor Neurons metabolism, Mutation, Neuromuscular Junction metabolism, Agrin genetics, Myasthenic Syndromes, Congenital genetics, Myasthenic Syndromes, Congenital metabolism
- Abstract
Congenital myasthenic syndromes (CMS) are predominantly characterized by muscle weakness and fatigability and can be caused by a variety of mutations in genes required for neuromuscular junction formation and maintenance. Among them, AGRN encodes agrin, an essential synaptic protein secreted by motoneurons. We have identified severe CMS patients with uncharacterized p.R1671Q, p.R1698P and p.L1664P mutations in the LG2 domain of agrin. Overexpression in primary motoneurons cultures in vitro and in chick spinal motoneurons in vivo revealed that the mutations modified agrin trafficking, leading to its accumulation in the soma and/or in the axon. Expression of mutant agrins in cultured cells demonstrated accumulation of agrin in the endoplasmic reticulum associated with induction of unfolded protein response (UPR) and impaired secretion in the culture medium. Interestingly, evaluation of the specific activity of individual agrins on AChR cluster formation indicated that when secreted, mutant agrins retained a normal capacity to trigger the formation of AChR clusters. To confirm agrin accumulation and secretion defect, iPS cells were derived from a patient and differentiated into motoneurons. Patient iPS-derived motoneurons accumulated mutant agrin in the soma and increased XBP1 mRNA splicing, suggesting UPR activation. Moreover, co-cultures of patient iPS-derived motoneurons with myotubes confirmed the deficit in agrin secretion and revealed a reduction in motoneuron survival. Altogether, we report the first mutations in AGRN gene that specifically affect agrin secretion by motoneurons. Interestingly, the three patients carrying these mutations were initially suspected of spinal muscular atrophy (SMA). Therefore, in the presence of patients with a clinical presentation of SMA but without mutation in the SMN1 gene, it can be worth to look for mutations in AGRN., (© 2022. The Author(s).)
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- 2022
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46. An integrative assessment of the plastic debris load in the Mediterranean Sea.
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Pedrotti ML, Lombard F, Baudena A, Galgani F, Elineau A, Petit S, Henry M, Troublé R, Reverdin G, Ser-Giacomi E, Kedzierski M, Boss E, and Gorsky G
- Subjects
- Environmental Monitoring, Environmental Pollution analysis, Mediterranean Sea, Plastics, Waste Products analysis
- Abstract
The Mediterranean Sea is recognized as one of the most polluted areas by floating plastics. During the Tara Mediterranean expedition, an extensive sampling of plastic debris was conducted in seven ecoregions, from Gibraltar to Lebanon with the aim of providing reliable estimates of regional differences in floating plastic loads and plastic characteristics. The abundance, size, surface, circularity and mass of 75,030 pieces were analyzed and classified in a standardized multi-parameter database. Their average abundance was 2.60 × 10
5 items km-2 (2.25 × 103 to 8.50 × 106 km-2 ) resulting in an estimate of about 650 billion plastic particles floating on the surface of the Mediterranean. This corresponds to an average of 660 metric tons of plastic, at the lower end of literature estimates. High concentrations of plastic were observed in the northwestern coastal regions, north of the Tyrrhenian Sea, but also off the western and central Mediterranean basins. The Levantine basin south of Cyprus had the lowest concentrations. A Lagrangian Plastic Pollution Index (LPPI) predicting the concentration of plastic debris was validated using the spatial resolution of the data. The advanced state of plastic degradation detected in the analyses led to the conclusion that stranding/fragmentation/resuspension is the key process in the dynamics of floating plastic in Mediterranean surface waters. This is supported by the significant correlation between pollution sources and areas of high plastic concentration obtained by the LPPI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)- Published
- 2022
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47. A lentiviral vector encoding fusion of light invariant chain and mycobacterial antigens induces protective CD4 + T cell immunity.
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Lopez J, Anna F, Authié P, Pawlik A, Ku MW, Blanc C, Souque P, Moncoq F, Noirat A, Hardy D, Sougakoff W, Brosch R, Guinet F, Charneau P, and Majlessi L
- Subjects
- Animals, Antigens, Bacterial, Antigens, Differentiation, B-Lymphocyte, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Genetic Vectors, Lentivirus, Mice, Mice, Inbred C57BL, Mycobacteriaceae, Histocompatibility Antigens Class II, Mycobacterium tuberculosis
- Abstract
Lentiviral vectors (LVs) are highly efficient at inducing CD8
+ T cell responses. However, LV-encoded antigens are processed inside the cytosol of antigen-presenting cells, which does not directly communicate with the endosomal major histocompatibility complex class II (MHC-II) presentation pathway. LVs are thus poor at inducing CD4+ T cell response. To overcome this limitation, we devised a strategy whereby LV-encoded antigens are extended at their N-terminal end with the MHC-II-associated light invariant chain (li), which contains an endosome-targeting signal sequence. When evaluated with an LV-encoded polyantigen composed of CD4+ T cell targets from Mycobacterium tuberculosis, intranasal vaccination in mice triggers pulmonary polyfunctional CD4+ and CD8+ T cell responses. Adjuvantation of these LVs extends the mucosal immunity to Th17 and Tc17 responses. A systemic prime and an intranasal boost with one of these LV induces protection against M. tuberculosis. This strategy improves the protective power of LVs against infections and cancers, where CD4+ T cell immunity plays an important role., Competing Interests: Declaration of interests P.C. is the founder and CSO of TheraVectys. J.L., F.A., P.A., M.-W.K., F.M., and A.N. are employees of TheraVectys. J.L., F.A., C.B., F.M., L.M., and P.C. are inventors of a pending patent directed to LV immunization able to induce CD4(+) T cells., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2022
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48. Reduced bacterial mortality and enhanced viral productivity during sinking in the ocean.
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Wei W, Chen X, Weinbauer MG, Jiao N, and Zhang R
- Subjects
- Bacteria, Membrane Transport Proteins, Oceans and Seas, Seawater microbiology, Ecosystem, Viruses
- Abstract
Particle sinking is an important process in the ocean, influencing the biogeochemical cycle and driving the long-term preservation of carbon into the deep sea via the biological pump. However, as an important component of marine ecosystems, the role of viruses during sinking is still poorly understood. Therefore, we performed a series of transplantation experiments in the South China Sea to simulate environmental changes during sinking and investigate their effects on viral eco-dynamics and life strategy. Our study demonstrated increased viral production but decreased virus-mediated bacterial mortality after transplantation. A larger burst size and switch from the lysogenic to lytic strategy were shown to contribute to enhanced viral productivity. We provide experimental evidence that surface viral ecological characteristics changed dramatically after transplantation into deep-sea waters, indicating a potential importance of viruses during vertical sinking in the ocean. This effect probably provides positive feedback on the efficiency of the biological pump., (© 2022. The Author(s).)
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- 2022
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49. Non-inferiority test for a continuous variable with a flexible margin in an active controlled trial: an application to the "Stratall ANRS 12110 / ESTHER" trial.
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Sandie AB, Molinari N, Wanjoya A, Kouanfack C, Laurent C, and Tchatchueng-Mbougua JB
- Subjects
- Adult, Humans, Margins of Excision, Research Design
- Abstract
Background: Non-inferiority trials are becoming increasingly popular in public health and clinical research. The choice of the non-inferiority margin is the cornerstone of such trials. Most of the time, the non-inferiority margin is fixed and constant, determined from historical trials as a fraction of the effect of the reference intervention. But in some circumstances, there may some uncertainty around the reference treatment that one would like to account for when performing the hypothesis testing. In this case, the non-inferiority margin is not fixed in advance and depends on the reference intervention estimate. Hence, the uncertainty surrounding the non-inferiority margin should be accounted for in statistical tests. In this work, we explore how to perform the non-inferiority test for a continuous variable with a flexible margin., Methods: We have proposed in this study, two procedures for the non-inferiority test with a flexible margin for continuous endpoints. The proposed test procedures are based on a test statistic and confidence interval approaches respectively. Simulations have been used to assess the performances and properties of the proposed test procedures. An application was done on a real-world clinical data, to assess the efficacy of clinical monitoring alone versus laboratory and clinical monitoring in HIV-infected adult patients., Results: Basically, for both proposed methods, the type I error estimate was not dependent on the values of the reference treatment. In the test statistic approach, the type 1 error rate estimate was approximatively equal to the nominal value. It has been found that the confidence interval level determined approximatively the level of significance. For a given nominal type I error α, the appropriate one- and two-sided confidence intervals should be with levels 1-α and 1-2α, respectively., Conclusions: Based on the type I error rate and power estimates, the proposed non-inferiority hypothesis test procedures had good performances and were applicable in practice., Trial Registration: ClinicalTrials.gov NCT00301561. Registered on March 13, 2006, url: https://clinicaltrials.gov/ct2/show/NCT00301561 ., (© 2022. The Author(s).)
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- 2022
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50. Synergistic Role of Quantitative Diffusion Magnetic Resonance Imaging and Structural Magnetic Resonance Imaging in Predicting Outcomes After Traumatic Brain Injury.
- Author
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Avesta A, Yendiki A, Perlbarg V, Velly L, Khalilzadeh O, Puybasset L, Galanaud D, and Gupta R
- Subjects
- Brain diagnostic imaging, Brain pathology, Diffusion Magnetic Resonance Imaging, Humans, Magnetic Resonance Imaging methods, Brain Injuries, Brain Injuries, Traumatic diagnostic imaging
- Abstract
Objective: This study aimed to assess if quantitative diffusion magnetic resonance imaging analysis would improve prognostication of individual patients with severe traumatic brain injury., Methods: We analyzed images of 30 healthy controls to extract normal fractional anisotropy ranges along 18 white-matter tracts. Then, we analyzed images of 33 patients, compared their fractional anisotropy values with normal ranges extracted from controls, and computed severity of injury to white-matter tracts. We also asked 2 neuroradiologists to rate severity of injury to different brain regions on fluid-attenuated inversion recovery and susceptibility-weighted imaging. Finally, we built 3 models: (1) fed with neuroradiologists' ratings, (2) fed with white-matter injury measures, and (3) fed with both input types., Results: The 3 models respectively predicted survival at 1 year with accuracies of 70%, 73%, and 88%. The accuracy with both input types was significantly better (P < 0.05)., Conclusions: Quantifying severity of injury to white-matter tracts complements qualitative imaging findings and improves outcome prediction in severe traumatic brain injury., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)
- Published
- 2022
- Full Text
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