Descriptor: "MESH : Phenotype" - Searchworks@Jio Institute Digital Library Search Results

Your search keyword '"MESH : Phenotype"' showing total 60 results

Start Over Descriptor "MESH : Phenotype"

60 results on '"MESH : Phenotype"'

1. Fcγ receptor expression on splenic macrophages in adult immune thrombocytopenia

Author: Bernard Bonnotte, Annemieke G. Laarhoven, Kim Santegoets, Philippe Saas, Maxime Samson, Gestur Vidarsson, Sylvain Audia, Olivier Facy, Timothy R D J Radstake, Pablo Ortega-Deballon, Nona Janikashvili, Laboratory of Translational Immunology [Utrecht, the Netherlands], University Medical Center [Utrecht], Service de médecine interne et immunologie clinique (SOC 1) [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (HOTE GREFFON), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Université de Franche-Comté (UFC), Sanquin Research, University of Amsterdam [Amsterdam] (UvA), Service de Chirurgie Digestive, Cancérologique, Générale, Endocrinienne et Urgences (CHU de Dijon), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université de Montpellier (UM), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Montpellier (UM), Landsteiner Laboratory, University Medical Center Utrecht [the Netherlands] ( UMC Utrecht ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), University of Amsterdam [Amsterdam] ( UvA ), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer ( LabEx LipSTIC ), Institut National de la Recherche Agronomique ( INRA ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Université Paris-Sud - Paris 11 ( UP11 ) -École pratique des hautes études ( EPHE ) -Institut Gustave Roussy ( IGR ) -Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ) -Université de Bourgogne ( UB ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Centre National de la Recherche Scientifique ( CNRS ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université de Franche-Comté ( UFC ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), and UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)
Subjects: Male, MESH: Spleen, Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2], MESH : Aged, MESH: Flow Cytometry, Immunoglobulin G, 0302 clinical medicine, MESH : Antigens, CD86, MESH: Autoimmune Diseases, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, CD86, MESH: Immunoglobulins, Intravenous, MESH : Receptors, IgG, MESH : Macrophages, MESH: Immunoglobulin G, MESH: Middle Aged, Immunoglobulins, Intravenous, Flow Cytometry, macrophages, MESH : Phenotype, Splenectomy, Antibody, IgG, Phagocytosis, Immunology, Immunoglobulins, Spleen, MESH: Receptors, IgG, MESH: Phenotype, MESH: Splenectomy, 03 medical and health sciences, MESH : Autoimmune Diseases, Genetic, MESH: Polymorphism, Genetic, Humans, MESH : Middle Aged, Polymorphism, Aged, Polymorphism, Genetic, MESH: Humans, Macrophages, MESH : Humans, MESH: Adult, 030104 developmental biology, spleen, B7-2 Antigen, MESH: Female, 0301 basic medicine, MESH : Polymorphism, Genetic, Receptor expression, medicine.disease_cause, Autoimmunity, immune system diseases, hemic and lymphatic diseases, Receptors, Immunology and Allergy, MESH : Female, MESH: Phagocytosis, MESH: Aged, biology, MESH : Thrombocytopenia, Fc receptors, autoimmunity, MESH : Adult, Middle Aged, Antigens, CD86, medicine.anatomical_structure, Phenotype, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Immunoglobulins, Intravenous, Intravenous, MESH : Spleen, Adult, MESH : Immunoglobulin G, MESH : Flow Cytometry, MESH : Male, chemical and pharmacologic phenomena, MESH: Antigens, CD86, Autoimmune Diseases, All institutes and research themes of the Radboud University Medical Center, MESH : Phagocytosis, medicine, Journal Article, Antigens, Opsonin, MESH : Splenectomy, MESH: Thrombocytopenia, Receptors, IgG, MESH: Macrophages, Original Articles, Thrombocytopenia, MESH: Male, biology.protein, 030215 immunology
Abstract: Summary Splenic macrophages play a key role in immune thrombocytopenia (ITP) pathogenesis by clearing opsonized platelets. Fcγ receptors (FcγR) participate in this phenomenon, but their expression on splenic macrophages and their modulation by treatment have scarcely been studied in human ITP. We aimed to compare the phenotype and function of splenic macrophages between six controls and 24 ITP patients and between ITP patients according to the treatments they received prior to splenectomy. CD86, human leucocyte antigen D-related (HLA-DR) and FcγR expression were measured by flow cytometry on splenic macrophages. The major FcγR polymorphisms were determined and splenic macrophage function was assessed by a phagocytosis assay. The expression of the activation markers CD86 and HLA-DR was higher on splenic macrophages during ITP compared to controls. While the expression of FcγR was not different between ITP and controls, the phagocytic function of splenic macrophages was reduced in ITP patients treated with intravenous immunoglobulin (IVIg) within the 2 weeks prior to splenectomy. The FCGR3A (158V/F) polymorphism, known to increase the affinity of FcγRIII to IgG, was over-represented in ITP patients. Thus, these are the first results arguing for the fact that the therapeutic use of IVIg during human chronic ITP does not modulate FcγR expression on splenic macrophages but decreases their phagocytic capabilities.
Published: 2017
Full Text: View/download PDF

2. Clinical similarities and differences of patients with X-linked lymphoproliferative syndrome type 1 (XLP-1/SAP deficiency) versus type 2 (XLP-2/XIAP deficiency)

Author: Pierre Bordigoni, Danielle Canioni, Michèle Milili, Nathalie Lambert, Claire Galambrun, Marie Ouachée-Chardin, Filomeen Haerynck, Françoise Le Deist, Despina Moshous, Christelle Lenoir, Stephanie Rigaud, Lionel Galicier, Fabien Touzot, Capucine Picard, Mohamed Hamidou, Hirokazu Kanegane, Ester Mejstrikova, Helen Chapel, Eduardo López-Granados, Stéphane Blanche, Alain Dabadie, Jana Pachlopnik Schmid, Pierre-Simon Rohrlich, Fabian Hauck, Geneviève de Saint Basile, Claudin Schiff, Jean-Louis Stephan, Alain Fischer, Isabelle Pellier, Nizar Mahlaoui, Sylvain Latour, Alain Fourmaintraux, Vincent Barlogis, IFR Necker-Enfants Malades (IRNEM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Developpement Normal et Pathologique du Système Immunitaire, Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service d'anatomie pathologique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Graduate School of Medicine, University of Toyama, Department of pediatrics, University of Oxford [Oxford], Teaching Hospital Motol and 2nd Medical School, Charles University, Department of Pediatric Hematology and Oncology, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Service d'immuno-hématologie pédiatrique [CHU Necker], Service d'Hématologie pédiatrique, Hôpital de la Timone, Marseille, Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service d'hématologie pédiatrique, Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Groupe Hospitalier Sud Réunion (GHSR), Centre Hospitalier Universitaire [Rennes], Centre de Référence Déficits Immunitaires Héréditaires (CEREDIH), Department of Paediatric Pulmonology, Ghent University Hospital, Service d'hématologie et immunologie pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Département de pédiatrie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, CHU Saint-Etienne, Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique Humaine des Maladies Infectieuses (Inserm U980), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'étude des Déficits Immunitaires, Assistance Publique-Hôpitaux de Paris, Service d'Immunologie et d'Hématologie Pédiatrique, Chaire Médecine expérimentale (A. Fischer), Collège de France (CdF (institution)), University of Oxford, Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Collège de France - Chaire Médecine expérimentale (A. Fischer), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre de Recherche en Cancérologie / Nantes - Angers (CRCNA), Centre hospitalier universitaire de Nantes (CHU Nantes)-Faculté de Médecine d'Angers-Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Laennec-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôtel-Dieu de Nantes, Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Saint-Jacques, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), IFR Necker-Enfants Malades ( IRNEM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Centre de Recherche en Cancérologie / Nantes - Angers ( CRCNA ), CHU Angers-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Laennec-Centre National de la Recherche Scientifique ( CNRS ) -Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille ( APHM ) - Hôpital de la Timone [CHU - APHM] ( TIMONE ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Groupe Hospitalier Sud Réunion ( GHSR ), Centre de Référence Déficits Immunitaires Héréditaires ( CEREDIH ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques, Centre d'Immunologie de Marseille - Luminy ( CIML ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Génétique Humaine des Maladies Infectieuses ( Inserm U980 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), and Assistance publique - Hôpitaux de Paris (AP-HP)
Subjects: Male, MESH : Retrospective Studies, MESH: X-Linked Inhibitor of Apoptosis Protein, MESH : Aged, MESH : Child, Preschool, Biochemistry, Cohort Studies, Immunoenzyme Techniques, Hypogammaglobulinemia, MESH: Lymphoproliferative Disorders, 0302 clinical medicine, MESH : Child, MESH: Child, hemic and lymphatic diseases, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH : Female, XIAP Deficiency, Signaling Lymphocytic Activation Molecule Associated Protein, X-Linked Lymphoproliferative Syndrome, Child, MESH: Cohort Studies, MESH: Aged, 0303 health sciences, MESH: Middle Aged, MESH : Lymphoproliferative Disorders, Intracellular Signaling Peptides and Proteins, MESH : Infant, Hematology, MESH : Adult, Middle Aged, MESH : Survival Rate, MESH: Infant, 3. Good health, Survival Rate, MESH : Phenotype, Phenotype, MESH: Young Adult, Child, Preschool, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, MESH : Mutation, Adult, medicine.medical_specialty, MESH: Mutation, Adolescent, MESH: Survival Rate, MESH : Male, Immunology, MESH : Young Adult, MESH : Cohort Studies, X-Linked Inhibitor of Apoptosis Protein, Biology, MESH: Phenotype, Virus, Young Adult, 03 medical and health sciences, MESH : Intracellular Signaling Peptides and Proteins, MESH : Immunoenzyme Techniques, MESH : Adolescent, MESH: Intracellular Signaling Peptides and Proteins, medicine, Humans, MESH : Middle Aged, MESH: Immunoenzyme Techniques, Aged, Retrospective Studies, 030304 developmental biology, MESH: Adolescent, Hemophagocytic lymphohistiocytosis, Cytopenia, MESH: Humans, MESH : Humans, MESH: Child, Preschool, Infant, X-linked lymphoproliferative disease, MESH: Adult, MESH: Retrospective Studies, Cell Biology, medicine.disease, Lymphoproliferative Disorders, MESH: Male, MESH : X-Linked Inhibitor of Apoptosis Protein, Mutation, Histopathology, MESH: Female, 030215 immunology
Abstract: X-linked lymphoproliferative syndromes (XLP) are primary immunodeficiencies characterized by a particular vulnerability toward Epstein-Barr virus infection, frequently resulting in hemophagocytic lymphohistiocytosis (HLH). XLP type 1 (XLP-1) is caused by mutations in the gene SH2D1A (also named SAP), whereas mutations in the gene XIAP underlie XLP type 2 (XLP-2). Here, a comparison of the clinical phenotypes associated with XLP-1 and XLP-2 was performed in cohorts of 33 and 30 patients, respectively. HLH (XLP-1, 55%; XLP-2, 76%) and hypogammaglobulinemia (XLP-1, 67%; XLP-2, 33%) occurred in both groups. Epstein-Barr virus infection in XLP-1 and XLP-2 was the common trigger of HLH (XLP-1, 92%; XLP-2, 83%). Survival rates and mean ages at the first HLH episode did not differ for both groups, but HLH was more severe with lethal outcome in XLP-1 (XLP-1, 61%; XLP-2, 23%). Although only XLP-1 patients developed lymphomas (30%), XLP-2 patients (17%) had chronic hemorrhagic colitis as documented by histopathology. Recurrent splenomegaly often associated with cytopenia and fever was preferentially observed in XLP-2 (XLP-1, 7%; XLP-2, 87%) and probably represents minimal forms of HLH as documented by histopathology. This first phenotypic comparison of XLP subtypes should help to improve the diagnosis and the care of patients with XLP conditions.
Published: 2011
Full Text: View/download PDF

3. Shifted, the Drosophila Ortholog of Wnt Inhibitory Factor-1, Controls the Distribution and Movement of Hedgehog

Author: Michael A. Halbisen, Bruno Glise, Alain Vincent, Michèle Crozatier, Steve Wise, Catherine A. Miller, David J. Olson, Seth S. Blair, Institut de Recherches et d'Etudes sur le Monde Arabe et Musulman (IREMAM), Sciences Po Aix - Institut d'études politiques d'Aix-en-Provence (IEP Aix-en-Provence)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre de biologie du développement (CBD), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Laboratoire Bordelais de Recherche en Informatique (LaBRI), Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Université Sciences et Technologies - Bordeaux 1-Université Bordeaux Segalen - Bordeaux 2, Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Anatomopathologie Haut-Lévêque (ANATOMOPATHOLOGIE), CHU, Clinical Neurology Oxford (CLINICAL NEUROLOGY), Hospital, Departement /u661 : Endocrinologie, Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de synthèse organique (DCSO), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), FLAveur, VIsion et Comportement du consommateur (FLAVIC), Etablissement National d'Enseignement Supérieur Agronomique de Dijon (ENESAD)-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Institut de Recherches et d'Etudes sur les Mondes Arabes et Musulmans (IREMAM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre de Biologie Intégrative (CBI), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB), École polytechnique (X)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherches et d'Etudes sur le Monde Arabe et Musulman ( IREMAM ), Sciences Po Aix - Institut d'études politiques d'Aix-en-Provence ( IEP Aix-en-Provence ) -Aix Marseille Université ( AMU ) -Centre National de la Recherche Scientifique ( CNRS ), Centre de biologie du développement ( CBD ), Université Paul Sabatier - Toulouse 3 ( UPS ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Bordelais de Recherche en Informatique ( LaBRI ), Centre National de la Recherche Scientifique ( CNRS ) -École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Université Sciences et Technologies - Bordeaux 1-Université Bordeaux Segalen - Bordeaux 2, Institut de Génomique Fonctionnelle ( IGF ), Centre National de la Recherche Scientifique ( CNRS ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Montpellier 1 ( UM1 ) -Université de Montpellier ( UM ), Anatomopathologie Haut-Lévêque ( ANATOMOPATHOLOGIE ), Clinical Neurology Oxford ( CLINICAL NEUROLOGY ), Université Montpellier 1 ( UM1 ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de synthèse organique ( DCSO ), École polytechnique ( X ) -Centre National de la Recherche Scientifique ( CNRS ), FLAveur, VIsion et Comportement du consommateur ( FLAVIC ), Etablissement National d'Enseignement Supérieur Agronomique de Dijon ( ENESAD ) -Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université de Bordeaux (UB)-École Nationale Supérieure d'Électronique, Informatique et Radiocommunications de Bordeaux (ENSEIRB)-Centre National de la Recherche Scientifique (CNRS), and Institut National de la Recherche Agronomique (INRA)-Etablissement National d'Enseignement Supérieur Agronomique de Dijon (ENESAD)-Université de Bourgogne (UB)
Subjects: Male, MESH: Signal Transduction, MESH : Molecular Sequence Data, MESH: Sequence Homology, Amino Acid, MESH: Drosophila, MESH : Animals, Genetically Modified, Sequence Homology, MESH : Models, Biological, MESH: Amino Acid Sequence, Wing, MESH: Cholesterol, 0302 clinical medicine, Models, Drosophila Proteins, MESH : Female, MESH: Animals, MESH : Cholesterol, Genetics, 0303 health sciences, biology, MESH : Amino Acid Sequence, Wnt signaling pathway, Signal transducing adaptor protein, MESH : Sequence Homology, Amino Acid, Hedgehog signaling pathway, Cell biology, MESH : Phenotype, Amino Acid, Imaginal disc, Cholesterol, Phenotype, MESH: Repressor Proteins, Drosophila, Female, MESH : Mutation, MESH : Repressor Proteins, MESH : Carrier Proteins, Drosophila melanogaster, Signal transduction, MESH : Heparan Sulfate Proteoglycans, Drosophila Protein, Signal Transduction, MESH: Mutation, animal structures, MESH: Drosophila Proteins, MESH : Male, Molecular Sequence Data, MESH : Wing, Genetically Modified, MESH: Carrier Proteins, MESH: Phenotype, General Biochemistry, Genetics and Molecular Biology, MESH: Animals, Genetically Modified, 03 medical and health sciences, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acid Sequence, MESH : Drosophila, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Molecular Biology, Hedgehog, Alleles, 030304 developmental biology, MESH : Signal Transduction, MESH: Humans, MESH: Molecular Sequence Data, MESH: Alleles, MESH : Humans, MESH: Models, Biological, Cell Biology, MESH : Drosophila Proteins, Biological, MESH: Wing, biology.organism_classification, MESH: Male, Repressor Proteins, Mutation, MESH: Heparan Sulfate Proteoglycans, MESH : Animals, MESH : Alleles, Carrier Proteins, MESH: Female, Heparan Sulfate Proteoglycans, 030217 neurology & neurosurgery, Developmental Biology
Abstract: SummaryWe here identify and characterize an extracellular modulator of Hedgehog signaling in Drosophila, Shifted. Shifted is required for high levels of long-range signaling in the developing wing imaginal disc. Surprisingly, shifted encodes the only Drosophila ortholog of the secreted vertebrate protein Wnt Inhibitory Factor-1 (WIF-1), whose known role is to bind to extracellular Wnts and inhibit their activity. However, Shifted does not regulate Hedgehog signaling by affecting Wingless or Wnt signaling. We show instead that Shifted is a secreted protein that acts over a long distance and is required for the normal accumulation of Hh protein and its movement in the wing. Our data further indicate that Shf interacts with Hh and the heparan sulfate proteoglycans. Therefore, we propose that Shf stabilizes the interaction between Hh and the proteoglycans, an unexpected role for a member of the WIF-1 family.
Published: 2005
Full Text: View/download PDF

4. Clinical and epidemiologic phenotypes of childhood asthma

Author: Depner , Martin, Fuchs , Oliver, Genuneit , Jon, Karvonen , Anne M, Hyvärinen , Anne, Kaulek , Vincent, Roduit , Caroline, Weber , Juliane, Schaub , Bianca, Lauener , Roger, Kabesch , Michael, Pfefferle , Petra Ina, Frey , Urs, Pekkanen , Juha, Dalphin , Jean-Charles, Riedler , Josef, Braun-Fahrländer , Charlotte, Von Mutius , Erika, Ege , Markus J, Renseigné , Non, Institute of Epidemiology, Universität Ulm, Department of Environmental Health, National Institute for Health and Welfare, Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Asthma and Allergy Department, University Children's Hospital-Ludwig Maximilians University, University of Zurich, Depner, Martin, Universität Ulm - Ulm University [Ulm, Allemagne], National Institute for Health and Welfare [Helsinki], Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)
Subjects: Pediatrics, MESH: Asthma, MESH : Prevalence, MESH: Respiratory Sounds, MESH : Prenatal Exposure Delayed Effects, MESH : Prospective Studies, MESH : Child, Preschool, Critical Care and Intensive Care Medicine, MESH : Agriculture, MESH: Regression Analysis, Cohort Studies, Atopy, MESH: Pregnancy, 0302 clinical medicine, MESH : Child, Pregnancy, Risk Factors, MESH: Risk Factors, MESH: Child, MESH : Regression Analysis, Epidemiology, Prevalence, MESH : Respiratory Sounds, MESH : Female, Prospective Studies, 030212 general & internal medicine, Child, MESH: Cohort Studies, MESH: Polymorphism, Single Nucleotide, MESH : Polymorphism, Single Nucleotide, Agriculture, MESH : Infant, MESH: Infant, Phenotype, MESH : Risk Factors, Latent class model, 3. Good health, Europe, MESH : Phenotype, Child, Preschool, Prenatal Exposure Delayed Effects, Regression Analysis, Female, medicine.symptom, MESH : Sensitivity and Specificity, 2706 Critical Care and Intensive Care Medicine, MESH: Agriculture, Pulmonary and Respiratory Medicine, medicine.medical_specialty, MESH: Environmental Exposure, MESH : Europe, MESH : Cohort Studies, 610 Medicine & health, MESH: Phenotype, MESH : Asthma, Polymorphism, Single Nucleotide, Sensitivity and Specificity, MESH: Prenatal Exposure Delayed Effects, [ SDV.EE.SANT ] Life Sciences [q-bio]/Ecology, environment/Health, 03 medical and health sciences, Wheeze, medicine, Humans, MESH: Prevalence, Respiratory Sounds, Asthma, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, MESH: Humans, Receiver operating characteristic, business.industry, MESH: Child, Preschool, MESH : Humans, Infant, Environmental Exposure, medicine.disease, MESH: Prospective Studies, MESH: Sensitivity and Specificity, MESH : Pregnancy, 030228 respiratory system, 10036 Medical Clinic, 2740 Pulmonary and Respiratory Medicine, Exhaled nitric oxide, MESH: Europe, business, MESH: Female, MESH : Environmental Exposure
Abstract: International audience; RATIONALE: Clinical and epidemiologic approaches have identified two distinct sets of classifications for asthma and wheeze phenotypes. OBJECTIVES: To compare epidemiologic phenotype definitions identified by latent class analysis (LCA) with clinical phenotypes based on patient histories, diagnostic work-up, and treatment responses. To relate phenotypes to genetic and environmental determinants as well as diagnostic and treatment-related parameters. METHODS: LCA was performed in an international multicenter birth cohort based on yearly questions about current wheeze until age 6 years. Associations of wheeze classes and clinical phenotypes with asthma-related characteristics such as atopy, lung function, fraction of exhaled nitric oxide, and medication use were calculated using regression models. MEASUREMENTS AND MAIN RESULTS: LCA identified five classes, which verified the clinically defined wheeze phenotypes with high sensitivity and specificity; the respective receiver operating characteristics curves displayed an area under the curve ranging from 84% (frequent wheeze) to 85% (asthma diagnosis) and 87% (unremitting wheeze) to 97% (recurrent unremitting wheeze). Recurrent unremitting wheeze was the most specific and unremitting wheeze at least once the most sensitive definition. The latter identified a subgroup of children with decreased lung function, increased genetic risk, and in utero smoke exposure (ODDS RATIO, 2.03; 95% CONFIDENCE INTERVAL, 1.12-3.68; P = 0.0191), but without established asthma diagnosis and treatment. CONCLUSIONS: Clinical phenotypes were well supported by LCA analysis. The hypothesis-free LCA phenotypes were a useful reference for comparing clinical phenotypes. Thereby, we identified children with clinically conspicuous but undiagnosed disease. Because of their high area under the curve values, clinical phenotypes such as (recurrent) unremitting wheeze emerged as promising alternative asthma definitions for epidemiologic studies.
Published: 2014
Full Text: View/download PDF

5. Hyperactivation of Alk induces neonatal lethality in knock-in AlkF1178L mice

Author: Jean-Loup Duband, Marie-France Champy, Marie-Christine Birling, Hamid Meziane, Evelyne Bloch-Gallego, Isabelle Janoueix-Lerosey, Thomas Bourgeois, Olivier Delattre, Jorge Gallego, Michel Huerre, Tania Sorg, Michel Roux, Boris Matrot, Lucille Lopez-Delisle, Estelle Durand, Cécile Pierre-Eugène, Bos, Mireille, Unité de génétique et biologie des cancers (U830), Université Paris Descartes - Paris 5 (UPD5)-Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Clinique de la Souris (ICS), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 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), PhenoPups : Preclinical Pediatric Contract Research Organization [Evry], Phenopups SAS [Evry], Neuroprotection du Cerveau en Développement / Promoting Research Oriented Towards Early Cns Therapies (PROTECT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Pathologie, Institut Curie [Paris], The U830 Inserm laboratory is supported bygrants from the Institut National du Cancer, the LigueNationale contre le Cancer (Equipe labellisée), theAssociation Hubert Gouin, Les Bagouz à Manon, les amisde Claire, la Fédération Enfants et Santé et la SociétéFrançaise de Lutte contre les Cancers et les Leucémiesde l’Enfant et l’Adolescent. L. L.-D. is the recipient ofa fellowship of the Ecole Polytechnique. The InstitutClinique de la Souris was funded by Inserm., Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), 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), Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Clinique de la Souris ( ICS ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Biologie du Développement ( LBD ), Centre National de la Recherche Scientifique ( CNRS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Neuroprotection du Cerveau en Développement ( PROTECT ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and INSTITUT CURIE
Subjects: Male, Congenital neuroblastoma, MESH : Behavior, Animal, MESH: Eating, Germline, MESH: Animals, Newborn, Feeding difficulty, brainstem, Immunoenzyme Techniques, Eating, Mice, Neuroblastoma, 0302 clinical medicine, neonatal lethality, hemic and lymphatic diseases, MESH: Behavior, Animal, Anaplastic lymphoma kinase, Anaplastic Lymphoma Kinase, MESH: Animals, feeding difficulties, 0303 health sciences, Behavior, Animal, plethysmography, MESH : Animals, Newborn, Respiration, 3. Good health, MESH : Phenotype, Phenotype, Oncology, 030220 oncology & carcinogenesis, Neonatal lethality, MESH: Receptor Protein-Tyrosine Kinases, MESH : Mutation, Research Paper, medicine.medical_specialty, MESH : Eating, MESH: Mutation, MESH : Male, Biology, MESH: Phenotype, 03 medical and health sciences, Germline mutation, MESH : Immunoenzyme Techniques, Internal medicine, Gene knockin, MESH : Mice, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, In patient, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Immunoenzyme Techniques, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, 030304 developmental biology, Gynecology, MESH: Respiration, MESH: Humans, MESH : Humans, Receptor Protein-Tyrosine Kinases, MESH : Receptor Protein-Tyrosine Kinases, MESH: Neuroblastoma, MESH: Male, MESH : Respiration, Endocrinology, Animals, Newborn, ALK, MESH : Genes, Lethal, Mutation, MESH : Neuroblastoma, Genes, Lethal, MESH : Animals, MESH: Genes, Lethal
Abstract: // Lucille Lopez-Delisle 1,2 , Cecile Pierre-Eugene 1,2 , Evelyne Bloch-Gallego 3,4 , Marie-Christine Birling 5 , Jean-Loup Duband 6,7 , Estelle Durand 8 , Thomas Bourgeois 8 , Boris Matrot 8,9 , Tania Sorg 5 , Michel Huerre 10 , Hamid Meziane 5 , Michel J. Roux 5 , Marie-France Champy 5 , Jorge Gallego 9 , Olivier Delattre 1,2 , Isabelle Janoueix-Lerosey 1,2 1 Inserm U830, Paris, France; 2 Institut Curie, Centre de Recherche, Paris, France; 3 Institut Cochin, Universite Paris Descartes, CNRS (UMR 8104), Paris, France; 4 Inserm, U1016, Paris, France; 5 Institut Clinique de la Souris, Illkirch-Graffenstaden, France; 6 Sorbonne Universites, Universite Pierre et Marie Curie-Paris 6, Paris, France; 7 CNRS, Laboratoire de Biologie du Developpement, Paris, France; 8 PhenoPups SAS, Evry, France; 9 Inserm U1141, Hopital Robert Debre, Paris, France; 10 Institut Curie, Departement de Pathologie, Paris, France. Correspondence: Isabelle Janoueix-Lerosey, email: // Keywords : ALK, brainstem, neonatal lethality, plethysmography, feeding difficulties Received : March 24, 2014 Accepted : April 01, 2014 Published : April 02, 2014 Abstract The ALK (Anaplastic Lymphoma Kinase) gene encodes a tyrosine kinase receptor preferentially expressed in the central and peripheral nervous systems. A syndromic presentation associating congenital neuroblastoma with severe encephalopathy and an abnormal shape of the brainstem has been described in patients harbouring de novo germline F1174V and F1245V ALK mutations. Here, we investigated the phenotype of knock-in (KI) mice bearing the Alk F1178L mutation (F1174L in human). Although heterozygous KI mice did not reproduce the severe breathing and feeding difficulties observed in human patients, behavioral tests documented a reduced activity during dark phases and an increased anxiety of mutated mice. Matings of heterozygotes yielded the expected proportions of wild-type, heterozygotes and homozygotes at birth but a high neonatal lethality was noticed for homozygotes. We documented Alk expression in several motor nuclei of the brainstem involved in the control of sucking and swallowing. Evaluation of basic physiological functions 12 hours after birth revealed slightly more apneas but a dramatic reduced milk intake for homozygotes compared to control littermates. Overall, our data demonstrate that Alk activation above a critical threshold is not compatible with survival in mice, in agreement with the extremely severe phenotype of patients carrying aggressive de novo ALK germline mutations.
Published: 2014
Full Text: View/download PDF

6. The cell wall pectic polymer rhamnogalacturonan-II is required for proper pollen tube elongation: implications of a putative sialyltransferase-like protein

Author: Arnaud Lehner, Marie Christine Kiefer-Meyer, Marie Dumont, Jean-Claude Mollet, Sophie Bouton, Patrice Lerouge, Aline Voxeur, Jérôme Pelloux, Laboratoire de Glycobiologie et Matrice Extracellulaire Végétale (Glyco-MEV), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Biologie des Plantes et Innovation - UR UPJV 3900 (BIOPI), Université de Picardie Jules Verne (UPJV)-Transfrontalière BioEcoAgro - UMR 1158 (BioEcoAgro), Université d'Artois (UA)-Université de Liège-Université de Picardie Jules Verne (UPJV)-Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL)-Université d'Artois (UA)-Université de Liège-Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Institut Jean-Pierre Bourgin (IJPB), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, University of Rouen, 'Trans Channel Wallnet' project, ERDF, Biologie des Plantes et Innovation (BIOPI), Université de Picardie Jules Verne (UPJV), Laboratoire de Glycobiologie et Matrice Extracellulaire Végétale ( Glyco-MEV ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Institut Jean-Pierre Bourgin ( IJPB ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, 0977 Unité associée de Biologie forestière, and Institut National de la Recherche Agronomique ( INRA )
Subjects: [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Arabidopsis thaliana, Polymers, [SDV]Life Sciences [q-bio], Mutant, Arabidopsis, MESH : Pollen Tube, Kdo, Plant Science, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], medicine.disease_cause, MESH : Arabidopsis Proteins, MESH : Arabidopsis, [ SDV.BBM.BC ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Cell Wall, Gene Expression Regulation, Plant, Genes, Reporter, MESH : Pectins, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], plant cell wall, [SDV.BDD]Life Sciences [q-bio]/Development Biology, RG-II, food and beverages, MESH : Sialyltransferases, [ SDV.BV.PEP ] Life Sciences [q-bio]/Vegetal Biology/Phytopathology and phytopharmacy, Articles, MESH : Genes, Reporter, Dha, MESH : Phenotype, [ SDV.BV.AP ] Life Sciences [q-bio]/Vegetal Biology/Plant breeding, Phenotype, Biochemistry, Germination, Organ Specificity, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Pectins, Pollen, Pollen tube, MESH : Mutation, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Biology, [ SDV.BC.IC ] Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Cell wall, MESH : Organ Specificity, [ SDV.BBM.MN ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular Networks [q-bio.MN], [ SDV.BDD.GAM ] Life Sciences [q-bio]/Development Biology/Gametogenesis, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, MESH : Pollen, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], MESH : Polymers, MESH : Cell Wall, Reporter gene, Arabidopsis Proteins, MESH : Sugar Acids, pectin motif, Wild type, [ SDV.BC.BC ] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], sialyltransferase-like protein, Sugar Acids, [ SDV.BIO ] Life Sciences [q-bio]/Biotechnology, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, biology.organism_classification, Molecular biology, pollen tube, Sialyltransferases, [SDV.BV.PEP]Life Sciences [q-bio]/Vegetal Biology/Phytopathology and phytopharmacy, [ CHIM.POLY ] Chemical Sciences/Polymers, [SDV.BV.AP]Life Sciences [q-bio]/Vegetal Biology/Plant breeding, Rhamnogalacturonan-II, Mutation, MESH : Gene Expression Regulation, Plant
Abstract: International audience; BACKGROUND AND AIMSRhamnogalacturonan-II (RG-II) is one of the pectin motifs found in the cell wall of all land plants. It contains sugars such as 2-keto-3-deoxy-d-lyxo-heptulosaric acid (Dha) and 2-keto-3-deoxy-d-manno-octulosonic acid (Kdo), and within the wall RG-II is mostly found as a dimer via a borate diester cross-link. To date, little is known regarding the biosynthesis of this motif. Here, after a brief review of our current knowledge on RG-II structure, biosynthesis and function in plants, this study explores the implications of the presence of a Golgi-localized sialyltransferase-like 2 (SIA2) protein that is possibly involved in the transfer of Dha or Kdo in the RG-II of Arabidopsis thaliana pollen tubes, a fast-growing cell type used as a model for the study of cell elongation.METHODS:Two heterozygous mutant lines of arabidopsis (sia2-1+/- and qrt1 × sia2-2+/-) were investigated. sia2-2+/- was in a quartet1 background and the inserted T-DNA contained the reporter gene β-glucuronidase (GUS) under the pollen-specific promoter LAT52. Pollen germination and pollen tube phenotype and growth were analysed both in vitro and in vivo by microscopy.KEY RESULTS:Self-pollination of heterozygous lines produced no homozygous plants in the progeny, which may suggest that the mutation could be lethal. Heterozygous mutants displayed a much lower germination rate overall and exhibited a substantial delay in germination (20 h of delay to reach 30 % of pollen grain germination compared with the wild type). In both lines, mutant pollen grains that were able to produce a tube had tubes that were either bursting, abnormal (swollen or dichotomous branching tip) or much shorter compared with wild-type pollen tubes. In vivo, mutant pollen tubes were restricted to the style, whereas the wild-type pollen tubes were detected at the base of the ovary..CONCLUSIONS:This study highlights that the mutation in arabidopsis SIA2 encoding a sialyltransferase-like protein that may transfer Dha or Kdo on the RG-II motif has a dramatic effect on the stability of the pollen tube cell wall.
Published: 2014
Full Text: View/download PDF

7. Characterization of the SigD regulon of C. difficile and its positive control of toxin production through the regulation of tcdR

Author: Marc Monot, Johann Peltier, Martine Pestel-Caron, Jean-Louis Pons, Olga Soutourina, Imane El Meouche, Bruno Dupuy, Groupe de Recherche sur les Antimicrobiens et les Micro-Organismes (GRAM 1.0), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU), Pathogénèse des Bactéries Anaérobies / Pathogenesis of Bacterial Anaerobes (PBA (U-Pasteur_6)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7), Cellule Pasteur, PRES Sorbonne Paris Cité-Université Paris Diderot - Paris 7 (UPD7), Ecosystème intestinal, probiotiques, antibiotiques (EA 4065), Université Paris Descartes - Paris 5 (UPD5), Funding was provided by the University of Rouen., Université Paris Diderot - Paris 7 (UPD7)-PRES Sorbonne Paris Cité, Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7), Groupe de Recherche sur les Antimicrobiens et les Micro-Organismes ( GRAM 1.0 ), Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Pathogénèse des Bactéries Anaérobies, Institut Pasteur [Paris], Université Paris Diderot - Paris 7 ( UPD7 ) -PRES Sorbonne Paris Cité, Ecosystème intestinal, probiotiques, antibiotiques ( EA 4065 ), and Université Paris Descartes - Paris 5 ( UPD5 )
Subjects: MESH : Protein Biosynthesis, Transcription, Genetic, Mutant, lcsh:Medicine, MESH : Transcriptome, MESH : Promoter Regions, Genetic, MESH: Base Sequence, Transcription (biology), Sigma factor, Gene expression, MESH : Bacterial Proteins, MESH: Gene Silencing, lcsh:Science, Promoter Regions, Genetic, MESH : Clostridium difficile, MESH: Bacterial Proteins, MESH : Consensus Sequence, Regulation of gene expression, Genetics, 0303 health sciences, MESH: Gene Expression Regulation, Bacterial, MESH: Genetic Complementation Test, Multidisciplinary, MESH : Protein Binding, DNA-Directed RNA Polymerases, MESH : Phenotype, Phenotype, Flagella, MESH: Protein Biosynthesis, MESH: Transcription Initiation Site, Transcription Initiation Site, MESH : Mutation, Research Article, Protein Binding, MESH : Gene Expression Regulation, Bacterial, MESH: Mutation, Bacterial Toxins, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Biology, MESH: Phenotype, MESH: Flagella, 03 medical and health sciences, Bacterial Proteins, MESH : DNA-Directed RNA Polymerases, Consensus Sequence, MESH : Gene Silencing, MESH: Promoter Regions, Genetic, Consensus sequence, Position-Specific Scoring Matrices, MESH: Protein Binding, Gene Silencing, MESH: Consensus Sequence, Gene, MESH: Clostridium difficile, 030304 developmental biology, Binding Sites, Base Sequence, MESH : Genetic Complementation Test, Clostridioides difficile, 030306 microbiology, MESH: Transcription, Genetic, MESH: Transcriptome, lcsh:R, Genetic Complementation Test, MESH : Transcription, Genetic, MESH: Position-Specific Scoring Matrices, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Gene Expression Regulation, Bacterial, MESH : Position-Specific Scoring Matrices, MESH: DNA-Directed RNA Polymerases, Regulon, MESH: Bacterial Toxins, MESH: Binding Sites, MESH : Transcription Initiation Site, Protein Biosynthesis, Mutation, MESH : Bacterial Toxins, lcsh:Q, MESH : Base Sequence, Transcriptome, MESH : Flagella, MESH : Binding Sites
Abstract: International audience; Clostridium difficile intestinal disease is mediated largely by the actions of toxins A (TcdA) and B (TcdB), whose production occurs after the initial steps of colonization involving different surface or flagellar proteins. In B. subtilis, the sigma factor SigD controls flagellar synthesis, motility, and vegetative autolysins. A homolog of SigD encoding gene is present in the C.difficile 630 genome. We constructed a sigD mutant in C. difficile 630 ∆erm to analyze the regulon of SigD using a global transcriptomic approach. A total of 103 genes were differentially expressed between the wild-type and the sigD mutant, including genes involved in motility, metabolism and regulation. In addition, the sigD mutant displayed decreased expression of genes involved in flagellar biosynthesis, and also of genes encoding TcdA and TcdB as well as TcdR, the positive regulator of the toxins. Genomic analysis and RACE-PCR experiments allowed us to characterize promoter sequences of direct target genes of SigD including tcdR and to identify the SigD consensus. We then established that SigD positively regulates toxin expression via direct control of tcdR transcription. Interestingly, the overexpression of FlgM, a putative anti-SigD factor, inhibited the positive regulation of motility and toxin synthesis by SigD. Thus, SigD appears to be the first positive regulator of the toxin synthesis in C. difficile.
Published: 2013
Full Text: View/download PDF

8. Toward a NOTCH1/FBXW7/RAS/PTEN-based oncogenetic risk classification of adult T-cell acute lymphoblastic leukemia: a Group for Research in Adult Acute Lymphoblastic Leukemia study

Author: Raouf Ben Abdelali, Véronique Lhéritier, Jean-Yves Cahn, Françoise Huguet, Norbert Ifrah, Agnès Buzyn, Noémie de Gunzburg, Elizabeth Macintyre, Vahid Asnafi, Dominique Payet-Bornet, Sébastien Maury, Jonathan Bond, Thibaud Leguay, Amélie Trinquand, Bertrand Nadel, André Delannoy, Kheira Beldjord, Hervé Dombret, Xavier Thomas, Jérôme Lambert, Ludovic Lhermitte, Hossein Mossafa, Etienne Lengliné, Yves Chalandon, Caroline Bonmati, Aline Tanguy-Schmidt, Centre d'Immunologie de Marseille - Luminy ( CIML ), Aix Marseille Université ( AMU ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Cytogénétique - Pasteur-Cerba, Laboratoire Pasteur-Cerba, Laboratoire d'Hématologie [Purpan], Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), TheREx, Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications [Grenoble] ( TIMC-IMAG ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ) -Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut polytechnique de Grenoble - Grenoble Institute of Technology ( Grenoble INP ) -IMAG-Centre National de la Recherche Scientifique ( CNRS ) -Université Grenoble Alpes ( UGA ), Centre de Recherche en Cancérologie de Lyon ( CRCL ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon ( HCL ), Hôpital de Jolimont, Haine-Saint-Paul and Cliniques Universitaires St Luc, Service hématologie, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service d'hématologie clinique [Avicenne], Université Paris 13 ( UP13 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Avicenne, Lymphocyte et cancer, IFR105-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre d'Immunologie de Marseille - Luminy (CIML), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service Hématologie - IUCT-Oncopole [CHU Toulouse], Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle IUCT [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], IFR105-Institut National de la Santé et de la Recherche Médicale (INSERM), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Université Toulouse III - Paul Sabatier (UT3), VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Centre de Recherche en Cancérologie de Lyon (CRCL), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Avicenne, Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Ras Proteins/genetics, Oncology, Pathology, MESH : F-Box Proteins, DNA Mutational Analysis, Cell Cycle Proteins, MESH : Gene Deletion, MESH: Receptor, Notch1, 0302 clinical medicine, MESH : Cell Cycle Proteins, Receptor, Notch1, MESH: DNA Mutational Analysis, Young adult, ddc:616, 0303 health sciences, Hazard ratio, PTEN Phosphohydrolase/genetics, hemic and immune systems, 3. Good health, MESH : Phenotype, MESH: Young Adult, 030220 oncology & carcinogenesis, Predictive value of tests, Cohort, F-Box Proteins/genetics, MESH : Proto-Oncogene Proteins, MESH: Membrane Proteins, MESH: ras Proteins, medicine.medical_specialty, MESH : Young Adult, MESH : DNA Mutational Analysis, MESH: Phenotype, MESH: PTEN Phosphohydrolase, Disease-Free Survival, Proto-Oncogene Proteins p21(ras), 03 medical and health sciences, MESH: Cell Cycle Proteins, Humans, PTEN, Ubiquitin-Protein Ligases/genetics, MESH : Predictive Value of Tests, MESH: Kaplan-Meier Estimate, Cell Cycle Proteins/genetics, Receptor, Notch1/genetics, [ SDV.IMM.II ] Life Sciences [q-bio]/Immunology/Innate immunity, MESH: Humans, Proportional hazards model, F-Box Proteins, MESH : Humans, MESH: Adult, MESH : Proportional Hazards Models, MESH: Ubiquitin-Protein Ligases, MESH : Membrane Proteins, MESH: Disease-Free Survival, Mutation, ras Proteins, Adult Acute Lymphoblastic Leukemia, MESH : Genetic Predisposition to Disease, MESH : Ubiquitin-Protein Ligases, MESH : GTP Phosphohydrolases, MESH: Female, Gene Deletion, Cancer Research, F-Box-WD Repeat-Containing Protein 7, Time Factors, MESH : Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Kaplan-Meier Estimate, MESH : PTEN Phosphohydrolase, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, GTP Phosphohydrolases, MESH: Proportional Hazards Models, MESH: Risk Factors, Risk Factors, hemic and lymphatic diseases, MESH : Female, biology, MESH : Receptor, Notch1, MESH: Genetic Predisposition to Disease, MESH : Adult, MESH : Risk Factors, MESH: Predictive Value of Tests, MESH: Precursor T-Cell Lymphoblastic Leukemia-Lymphoma, Phenotype, MESH : Disease-Free Survival, Female, MESH : Mutation, MESH : Time Factors, Adult, MESH: Mutation, MESH: GTP Phosphohydrolases, Ubiquitin-Protein Ligases, MESH : Male, MESH: F-Box Proteins, MESH: Multivariate Analysis, MESH : Kaplan-Meier Estimate, Young Adult, Predictive Value of Tests, Proto-Oncogene Proteins, Internal medicine, medicine, Genetic Predisposition to Disease, Membrane Proteins/genetics, Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/classification/genetics/mortality/therapy, Proportional Hazards Models, 030304 developmental biology, business.industry, MESH: Time Factors, PTEN Phosphohydrolase, Membrane Proteins, MESH : Multivariate Analysis, GTP Phosphohydrolases/genetics, MESH: Male, MESH: Proto-Oncogene Proteins, Proto-Oncogene Proteins/genetics, MESH: Gene Deletion, Multivariate Analysis, biology.protein, MESH : ras Proteins, business
Abstract: Purpose The Group for Research in Adult Acute Lymphoblastic Leukemia (GRAALL) recently reported a significantly better outcome in T-cell acute lymphoblastic leukemia (T-ALL) harboring NOTCH1 and/or FBXW7 (N/F) mutations compared with unmutated T-ALL. Despite this, one third of patients with N/F-mutated T-ALL experienced relapse. Patients and Methods In a series of 212 adult T-ALLs included in the multicenter randomized GRAALL-2003 and -2005 trials, we searched for additional N/K-RAS mutations and PTEN defects (mutations and gene deletion). Results N/F mutations were identified in 143 (67%) of 212 patients, and lack of N/F mutation was confirmed to be associated with a poor prognosis. K-RAS, N-RAS, and PTEN mutations/deletions were identified in three (1.6%) of 191, 17 (8.9%) of 191, and 21 (12%) of 175 patients, respectively. The favorable prognostic significance of N/F mutations was restricted to patients without RAS/PTEN abnormalities. These observations led us to propose a new T-ALL oncogenetic classifier defining low-risk patients as those with N/F mutation but no RAS/PTEN mutation (97 of 189 patients; 51%) and all other patients (49%; including 13% with N/F and RAS/PTEN mutations) as high-risk patients. In multivariable analysis, this oncogenetic classifier remained the only significant prognostic covariate (event-free survival: hazard ratio [HR], 3.2; 95% CI, 1.9 to 5.15; P < .001; and overall survival: HR, 3.2; 95% CI, 1.9 to 5.6; P < .001). Conclusion These data demonstrate that the presence of N/F mutations in the absence of RAS or PTEN abnormalities predicts good outcome in almost 50% of adult T-ALL. Conversely, the absence of N/F or presence of RAS/PTEN alterations identifies the remaining cohort of patients with poor prognosis.
Published: 2013
Full Text: View/download PDF

9. Arabidopsis thaliana nicotianamine synthase 4 is required for proper response to iron deficiency and to cadmium exposure

Author: Jeremy Astier, Olivier Lamotte, Frédéric Gaymard, Emmanuel Koen, Jossia Boucherez, Angélique Besson-Bard, David Wendehenne, Pierre Richaud, Céline Duc, Antoine Gravot, Agroécologie [Dijon], Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Biochimie et Physiologie Moléculaire des Plantes (BPMP), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Amélioration des Plantes et Biotechnologies Végétales (APBV), Institut National de la Recherche Agronomique (INRA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-AGROCAMPUS OUEST, Bioénergie et Microalgues (EBM), Institut de Biosciences et Biotechnologies d'Aix-Marseille (ex-IBEB) (BIAM), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Agence Nationale de la Recherche [BLAN07-2_184783], University of Burgundy (BQR project), Burgundy State (PARI AGRALE 8 project), French Ministry of Agriculture, Ministere de l'Education Nationale, de la Recherche et de la Technologie, Region Languedoc-Roussillon, Institut National de la Recherche Agronomique, Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-AGROCAMPUS OUEST, Environnement, Bioénergie, Microalgues et Plantes (EBMP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Université de Montpellier (UM)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), AGROCAMPUS OUEST-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Recherche Agronomique (INRA), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Biochimie et Physiologie Moléculaire des Plantes ( BPMP ), Centre international d'études supérieures en sciences agronomiques ( Montpellier SupAgro ) -Institut national de la recherche agronomique [Montpellier] ( INRA Montpellier ) -Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ) -Institut national d’études supérieures agronomiques de Montpellier ( Montpellier SupAgro ), Amélioration des Plantes et Biotechnologies Végétales ( APBV ), Institut National de la Recherche Agronomique ( INRA ) -Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -AGROCAMPUS OUEST, Laboratoire de Bioénergétique et Biotechnologie des Bactéries et Microalgues ( L3BM ), and Commissariat à l'énergie atomique et aux énergies alternatives ( CEA )
Subjects: 0106 biological sciences, [ SDV.BV ] Life Sciences [q-bio]/Vegetal Biology, MESH : Azetidinecarboxylic Acid, FMN Reductase, Arabidopsis thaliana, Mutant, Arabidopsis, Gene Expression, Plant Science, 01 natural sciences, MESH : Cation Transport Proteins, MESH : Iron, MESH : Arabidopsis Proteins, Nicotianamine synthase, MESH : Plants, Genetically Modified, chemistry.chemical_compound, MESH : Arabidopsis, Gene Expression Regulation, Plant, Gene expression, MESH: Genes, Plant, MESH : DNA, Bacterial, Homeostasis, MESH: Arabidopsis, Nicotianamine, MESH: Stress, Physiological, Cation Transport Proteins, MESH : Adaptation, Physiological, MESH : Cadmium, 2. Zero hunger, chemistry.chemical_classification, 0303 health sciences, Cadmium, MESH: Iron, biology, General Medicine, Iron Deficiencies, Plants, Genetically Modified, Adaptation, Physiological, MESH: Azetidinecarboxylic Acid, MESH : Phenotype, Phenotype, Biochemistry, MESH: Homeostasis, MESH : Homeostasis, MESH : Mutation, Azetidinecarboxylic Acid, DNA, Bacterial, MESH: Gene Expression, MESH: Mutation, Iron, MESH: Cadmium, chemistry.chemical_element, MESH: Ferritins, MESH: Arabidopsis Proteins, MESH: Alkyl and Aryl Transferases, Genes, Plant, MESH: Phenotype, 03 medical and health sciences, MESH: Cation Transport Proteins, Stress, Physiological, Iron homeostasis, Genetics, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Iron deficiency (plant disorder), MESH: Gene Expression Regulation, Plant, MESH : Genes, Plant, MESH : Alkyl and Aryl Transferases, MESH : Stress, Physiological, 030304 developmental biology, MESH : FMN Reductase, Alkyl and Aryl Transferases, Arabidopsis Proteins, Iron deficiency, Nitric oxide, biology.organism_classification, MESH: Adaptation, Physiological, MESH: DNA, Bacterial, MESH : Gene Expression, Enzyme, chemistry, MESH: FMN Reductase, MESH: Plants, Genetically Modified, Ferritins, Mutation, biology.protein, MESH : Ferritins, Agronomy and Crop Science, MESH : Gene Expression Regulation, Plant, 010606 plant biology & botany
Abstract: International audience; The nicotianamine synthase (NAS) enzymes catalyze the formation of nicotianamine (NA), a non-proteinogenic amino acid involved in iron homeostasis. We undertook the functional characterization of AtNAS4, the fourth member of the Arabidopsis thaliana NAS gene family. A mutant carrying a T-DNA insertion in AtNAS4 (atnas4), as well as lines overexpressing AtNAS4 both in the atnas4 and the wild-type genetic backgrounds, were used to decipher the role of AtNAS4 in NA synthesis, iron homeostasis and the plant response to iron deficiency or cadmium supply. We showed that AtNAS4 is an important source for NA. Whereas atnas4 had normal growth in iron-sufficient medium, it displayed a reduced accumulation of ferritins and exhibited a hypersensitivity to iron deficiency. This phenotype was rescued in the complemented lines. Under iron deficiency, atnas4 displayed a lower expression of the iron uptake-related genes IRT1 and FRO2 as well as a reduced ferric reductase activity. Atnas4 plants also showed an enhanced sensitivity to cadmium while the transgenic plants overexpressing AtNAS4 were more tolerant. Collectively, our data, together with recent studies, support the hypothesis that AtNAS4 displays an important role in iron distribution and is required for proper response to iron deficiency and to cadmium supply.
Published: 2013
Full Text: View/download PDF

10. Type II TGFβ receptor modulates chondrocyte phenotype

Author: Elise Duval, Sylvain Leclercq, Catherine Baugé, Philippe Galéra, Nicolas Girard, Karim Boumediene, David Ollitrault, Normandie Université ( NU ), Microenvironnement cellulaire et pathologie ( MILPAT ), Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Département de chirurgie orthopédique, Clinique Saint Martin, Normandie Université (NU), Microenvironnement et Pathologies du Cartilage (BioConnecT), Microenvironnement cellulaire et pathologie (MILPAT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Département de chirurgie orthopédique [Hôpital privé Saint Martin Caen], and Hôpital Privé Saint Martin Caen
Subjects: Cartilage, Articular, MESH : Bone Marrow, Aging, MESH : RNA, Messenger, MESH : Transcription Factors, MESH : Receptors, Transforming Growth Factor beta, MESH : Chondrogenesis, MESH : Alginates, MESH : Blotting, Western, Osteoarthritis, Hip, 0302 clinical medicine, MESH: Aggrecans, MESH: Osteoarthritis, MESH : Collagen Type II, Cells, Cultured, Regulation of gene expression, Aged, 80 and over, 0303 health sciences, [ SDV.MHEP.PHY ] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], MESH: Bone Marrow Cells, Cell Differentiation, General Medicine, MESH: Transcription Factors, Middle Aged, Cell biology, MESH : Phenotype, medicine.anatomical_structure, Phenotype, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, 030220 oncology & carcinogenesis, MESH: Alginates, Disease Progression, MESH: Bone Marrow, MESH: Receptors, Transforming Growth Factor beta, MESH : Cell Differentiation, MESH: Chondrogenesis, Signal Transduction, MESH: Cell Differentiation, Blotting, Western, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, MESH: Phenotype, Real-Time Polymerase Chain Reaction, Chondrocyte, Article, MESH : Chondrocytes, MESH : Cartilage, [ SDV.MHEP.RSOA ] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, 03 medical and health sciences, Transforming Growth Factor beta2, Chondrocytes, MESH: Chondrocytes, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], MESH : Aggrecans, Gene silencing, MESH: Blotting, Western, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, RNA, Messenger, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Aggrecan, MESH: Transforming Growth Factor beta, 030304 developmental biology, MESH: RNA, Messenger, Aged, MESH: Humans, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, Mesenchymal stem cell, MESH : Humans, MESH: Collagen Type II, Chondrogenesis, Molecular biology, MESH : Osteoarthritis, MESH : Transforming Growth Factor beta, Gene Expression Regulation, MESH: Cartilage, Ectopic expression, Geriatrics and Gerontology, Transforming growth factor, MESH : Bone Marrow Cells
Abstract: International audience; Aging is one of the major risk factors of osteoarthritis. This pathology during which chondrocytes undergo modifications of their phenotype may result from alteration of transforming growth factor β (TGFβ) signaling. This study investigates the role of TGFβ response in the process of chondrocyte dedifferentiation/redifferentiation. Dedifferentiation was induced by successive passages of human articular chondrocytes, whereas their redifferentiation was performed by three-dimensional culture in alginate. Human mesenchymal stem cells were obtained from bone marrow and differentiated into chondrocyte-like phenotype by three-dimensional culture, embedded in the same scaffold. Protein and mRNA levels were analyzed by Western blot and real-time reverse transcription PCR. Regulatory mechanism was investigated using specific inhibitors (mithramycin), mRNA silencing or decoy oligonucleotides, and expression vectors. Chondrocyte dedifferentiation interfered with TGFβ signaling by decreasing TβRII mRNA and protein levels and subsequent TGFβ response. TβRII ectopic expression in passaged chondrocytes permitted to increase the expression of several matrix genes, such as aggrecan or type II collagen. Redifferentiation of passaged chondrocytes permitted to restore, at least in part, TβRII expression and was related to differentiation of human bone marrow mesenchymal stem cells toward chondrocytes, where both specific protein 1 (Sp1) and TβRII mRNA levels were increased. Moreover, Sp1 manipulation by silencing or ectopic expression and pharmacologic inhibition revealed a link between expression levels of this transcriptional factor, which is crucial for constitutive expression of TβRII in cartilage, and TGFβ response. Therefore, these data permit us to suggest an important role of TβRII expression in the maintenance of chondrocyte phenotype, which is altered with age, and bring new insights in our understanding of chondrogenesis process.
Published: 2013
Full Text: View/download PDF

11. Identification of quorum sensing-controlled genes in Burkholderia ambifaria

Author: Annelise Chapalain, Jonathan Perreault, Ludovic Vial, Eric Déziel, Natacha Laprade, Valérie Dekimpe, Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), Laboratoire d'Ecologie Microbienne - UMR 5557 (LEM), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Ecole Nationale Vétérinaire de Lyon (ENVL)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), This study was supported by a Canadian Institutes of Health Research (CIHR) Operating grant to E. D., Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Lyon (ENVL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique (INRA)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS), Institut Armand Frappier ( INRS-IAF ), Institut National de la Recherche Scientifique [Québec] ( INRS ) -Réseau International des Instituts Pasteur ( RIIP ) -Institut Armand Frappier, Ecologie microbienne ( EM ), Centre National de la Recherche Scientifique ( CNRS ) -Ecole Nationale Vétérinaire de Lyon ( ENVL ) -Université Claude Bernard Lyon 1 ( UCBL ), and Université de Lyon-Université de Lyon-Institut National de la Recherche Agronomique ( INRA ) -VetAgro Sup ( VAS )
Subjects: MESH : Escherichia coli, Antifungal Agents, MESH: Drosophila, [SDV]Life Sciences [q-bio], random mutagenesis, Siderophores, MESH: Virulence, MESH : Ligases, MESH: Quorum Sensing, Ligases, chemistry.chemical_compound, MESH : Bacterial Proteins, MESH : Siderophores, MESH: Animals, MESH: Bacterial Proteins, Original Research, MESH : Burkholderia cepacia complex, 0303 health sciences, MESH: Gene Expression Regulation, Bacterial, biology, Virulence, secondary metabolites, MESH: Escherichia coli, Burkholderia cepacia complex, MESH : Virulence, Burkholderia ambifaria, Quorum Sensing, MESH : beta-Galactosidase, MESH : Pyrrolnitrin, MESH: beta-Galactosidase, Pyrrolnitrin, MESH : Phenotype, Phenotype, MESH: Ligases, Drosophila, MESH : Gene Expression Regulation, Bacterial, MESH: Computational Biology, Burkholderia, MESH : Antifungal Agents, MESH: Pyrrolnitrin, Mutagenesis (molecular biology technique), Rhizobacteria, MESH: Phenotype, Microbiology, 03 medical and health sciences, Bacterial Proteins, Escherichia coli, Animals, MESH : Drosophila, MESH: Siderophores, 030304 developmental biology, MESH: Burkholderia cepacia complex, [ SDV ] Life Sciences [q-bio], 030306 microbiology, Computational Biology, Gene Expression Regulation, Bacterial, biology.organism_classification, beta-Galactosidase, MESH: Antifungal Agents, MESH : Quorum Sensing, Quorum sensing, chemistry, Antifungal molecules, MESH : Animals, MESH : Computational Biology
Abstract: International audience; The Burkholderia cepacia complex (Bcc) comprises strains with a virulence potential toward immunocompromised patients as well as plant growth-promoting rhizobacteria (PGPR). Owing to the link between quorum sensing (QS) and virulence, most studies among Bcc species have been directed toward QS of pathogenic bacteria. We have investigated the QS of B. ambifaria, a PGPR only infrequently recovered from patients. The cepI gene, responsible for the synthesis of the main signaling molecule N-octanoylhomoserine lactone (C8 -HSL), was inactivated. Phenotypes of the B. ambifaria cepI mutant we observed, such as increased production of siderophores and decreased proteolytic and antifungal activities, are in agreement with those of other Bcc cepI mutants. The cepI mutant was then used as background strain for a whole-genome transposon-insertion mutagenesis strategy, allowing the identification of 20 QS-controlled genes, corresponding to 17 loci. The main functions identified are linked to antifungal and antimicrobial properties, as we have identified QS-controlled genes implicated in the production of pyrrolnitrin, burkholdines (occidiofungin-like molecules), and enacyloxins. This study provides insights in the QS-regulated functions of a PGPR, which could lead to beneficial potential biotechnological applications.
Published: 2013
Full Text: View/download PDF

12. Parental electrocardiographic screening identifies a high degree of inheritance for congenital and childhood nonimmune isolated atrioventricular block

Author: Hervé Le Marec, Caroline Bonnet, Jean-René Lusson, Raphaël P. Martins, Jean-Jacques Schott, Francis Rouault, Alban-Elouen Baruteau, Jean-Benoit Thambo, Christian Dina, Elisabeth Villain, François Godart, Philippe Mabo, Vincent Probst, Alain Fraisse, François Marçon, Albin Behaghel, Véronique Gournay, Sophie Guillaumont, Yves Dulac, Jean-Marc Schleich, Stéphanie Chatel, Swanny Fouchard, Alain Chantepie, Béatrice Delasalle, Jean-Claude Daubert, unité de recherche de l'institut du thorax UMR1087 UMR6291 ( ITX ), Université de Nantes ( UN ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Department de Chirurgie cardiaque des cardiopathies congénitales, Centre chirurgical Marie Lannelongue, Service de cardiologie et maladies vasculaires, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Pontchaillou-CHU Pontchaillou [Rennes], CIC-IT Rennes, Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire Traitement du Signal et de l'Image ( LTSI ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de génie des procédés - environnement - agroalimentaire ( GEPEA ), Mines Nantes ( Mines Nantes ) -Université de Nantes ( UN ) -Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique ( ONIRIS ) -Centre National de la Recherche Scientifique ( CNRS ), Service de cardiologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service cardiologie pédiatrique [Bordeaux], CHU Bordeaux [Bordeaux], Service de Cardiologie Infantile [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Service de cardiologie pédiatrique [Nantes], Centre hospitalier universitaire de Nantes ( CHU Nantes ), Cabinet de Cardiologie pédiatrique, Service de cardiologie pédiatrique [Tours], CHU Tours, Service de cardiologie Pédiatrique [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ), Service de cardiologie Pédiatrique [Lille], Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Service de cardiologie pédiatrique et congénitale adulte [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service de cardiologie Pédiatrique [Marseille], Hôpital de la Timone [CHU - APHM] ( TIMONE ), Service de cardiologie [Clermont-Ferrand], CHU Clermont-Ferrand, Service pédiatrie-cardiologie, CHU Toulouse [Toulouse]-Hôpital des Enfants, unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de cardiologie et maladies vasculaires [Rennes] = Cardiac, Thoracic, and Vascular Surgery [Rennes], CHU Pontchaillou [Rennes], Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Traitement du Signal et de l'Image (LTSI), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de génie des procédés - environnement - agroalimentaire (GEPEA), Mines Nantes (Mines Nantes)-Université de Nantes - UFR des Sciences et des Techniques (UN UFR ST), Université de Nantes (UN)-Université de Nantes (UN)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital de la Timone [CHU - APHM] (TIMONE), Service de Cardiologie Maladies Vasculaires [CHU Clermont-Ferrand], CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, CHU Toulouse [Toulouse], Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre Chirurgical Marie Lannelongue (CCML), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Nantes (UN)-Université de Nantes (UN)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Centre National de la Recherche Scientifique (CNRS), Service Cardiologie pédiatrique [CHU Toulouse], Pôle Enfants [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Le Corre, Morgane, and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)
Subjects: Male, Parents, MESH : Retrospective Studies, Heart malformation, MESH : NAV1.5 Voltage-Gated Sodium Channel, MESH : Prevalence, MESH : Aged, Electrocardiography, 0302 clinical medicine, MESH: Pregnancy, MESH : Child, Pregnancy, Prenatal Diagnosis, MESH: Child, Medicine, Sinus rhythm, genetics, Child, 0303 health sciences, MESH: Middle Aged, MESH: Genetic Testing, MESH : Infant, MESH: Infant, 3. Good health, MESH : Phenotype, MESH: Young Adult, MESH : Electrocardiography, Child, Preschool, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, conduction, MESH : Young Adult, Prenatal diagnosis, MESH: Phenotype, Sudden death, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Physiology (medical), MESH : Adolescent, MESH : Genetic Testing, Humans, MESH : Middle Aged, Genetic Testing, MESH: Prenatal Diagnosis, MESH : Prenatal Diagnosis, MESH: Prevalence, Aged, Retrospective Studies, [SDV.IB] Life Sciences [q-bio]/Bioengineering, MESH: Adolescent, MESH: Parents, MESH: Humans, MESH: Child, Preschool, MESH : Humans, Infant, MESH: Adult, MESH: Retrospective Studies, medicine.disease, MESH : Pregnancy, MESH : Genetic Predisposition to Disease, Atrioventricular block, MESH: Female, Pediatrics, ECG screening, 030204 cardiovascular system & hematology, MESH : Child, Preschool, NAV1.5 Voltage-Gated Sodium Channel, atrioventricular block, Prevalence, Mass Screening, MESH : Female, [ SDV.IB ] Life Sciences [q-bio]/Bioengineering, Family history, MESH : Parents, MESH: Aged, MESH: Infant, Newborn, MESH: Genetic Predisposition to Disease, Middle Aged, MESH : Adult, [ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH : Atrioventricular Block, Phenotype, Female, [SDV.IB]Life Sciences [q-bio]/Bioengineering, medicine.symptom, Adult, Adolescent, pediatrics, MESH : Male, MESH : Infant, Newborn, Asymptomatic, Young Adult, MESH: Atrioventricular Block, Genetic Predisposition to Disease, MESH: Mass Screening, PR interval, 030304 developmental biology, MESH : Mass Screening, business.industry, Infant, Newborn, MESH: NAV1.5 Voltage-Gated Sodium Channel, MESH: Male, MESH: Electrocardiography, business
Abstract: Background— The origin of congenital or childhood nonimmune isolated atrioventricular (AV) block remains unknown. We hypothesized that this conduction abnormality in the young may be a heritable disease. Methods and Results— A multicenter retrospective study (13 French referral centers, from 1980–2009) included 141 children with AV block diagnosed in utero, at birth, or before 15 years of age without structural heart abnormalities and without maternal antibodies. Parents and matched control subjects were investigated for family history and for ECG screening. In parents, a family history of sudden death or progressive cardiac conduction defect was found in 1.4% and 11.1%, respectively. Screening ECGs from 130 parents (mean age 42.0±6.8 years, 57 couples) were compared with those of 130 matched healthy control subjects. All parents were asymptomatic and in sinus rhythm, except for 1 with undetected complete AV block. Conduction abnormalities were more frequent in parents than in control subjects, found in 50.8% versus 4.6%, respectively ( P P P P SCN5A mutation screening identified 2 mutations in 2 patients among 97 children. Conclusions— ECG screening in parents of children affected by idiopathic AV block revealed a high prevalence of conduction abnormalities. These results support the hypothesis of an inheritable trait in congenital and childhood nonimmune isolated AV block.
Published: 2012
Full Text: View/download PDF

13. Depletion of the p43 mitochondrial T3 receptor in mice affects skeletal muscle development and activity

Author: François Casas, Stéphanie Grandemange, Laurence Pessemesse, Pascal Seyer, Gérard Cabello, Audrey Schlernitzauer, Sandra Kaminski, Jonathan Levin, Chamroeun Sar, Chantal Wrutniak-Cabello, François Bertrand Favier, Dynamique Musculaire et Métabolisme (DMEM), Institut National de la Recherche Agronomique (INRA)-Université de Montpellier (UM), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs (INM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Signalisation, Génomique et Recherche Translationnelle en Oncologie (SIGRETO), Université Henri Poincaré - Nancy 1 (UHP), Institut de Génomique Fonctionnelle (IGF), Centre National de la Recherche Scientifique (CNRS)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 1 (UM1)-Université de Montpellier (UM), Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Dynamique Musculaire et Métabolisme ( DMEM ), Institut National de la Recherche Agronomique ( INRA ) -Université de Montpellier ( UM ), Institut des Neurosciences de Montpellier - Déficits sensoriels et moteurs ( INM ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Signalisation, Génomique et Recherche Translationnelle en Oncologie ( SIGRETO ), Université Henri Poincaré - Nancy 1 ( UHP ), Institut de Génomique Fonctionnelle ( IGF ), Centre National de la Recherche Scientifique ( CNRS ) -Université Montpellier 2 - Sciences et Techniques ( UM2 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Montpellier 1 ( UM1 ) -Université de Montpellier ( UM ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), and Casas, Francois
Subjects: Male, MESH: Muscle Contraction, MESH: DNA Replication, Mitochondrion, MESH : Muscle Fibers, Fast-Twitch, [ SDV.BA ] Life Sciences [q-bio]/Animal biology, Biochemistry, MESH: Mice, Knockout, Muscle hypertrophy, Mice, 0302 clinical medicine, MESH : Lipid Metabolism, MESH : DNA, Mitochondrial, MESH: Animals, MESH: Oxygen Consumption, MESH : Muscle, Skeletal, MESH : Oxygen Consumption, metabolism, thyroid hormone, MESH : Electron Transport, MESH: Lipid Metabolism, Mice, Knockout, 0303 health sciences, MESH: Muscle, Skeletal, Receptors, Thyroid Hormone, MESH: Hypertrophy, [SDV.BA]Life Sciences [q-bio]/Animal biology, MESH : Receptors, Thyroid Hormone, MESH : Hypertrophy, Mitochondria, MESH : Phenotype, medicine.anatomical_structure, Phenotype, Muscle Fibers, Fast-Twitch, MESH : Mitochondria, medicine.symptom, ITGA7, MESH : DNA Replication, Biotechnology, Mitochondrial DNA replication, Muscle contraction, Muscle Contraction, DNA Replication, medicine.medical_specialty, MESH: Mitochondria, MESH : Male, MESH : Mice, Inbred C57BL, Biology, MESH: Phenotype, DNA, Mitochondrial, Electron Transport, 03 medical and health sciences, Oxygen Consumption, MESH: Mice, Inbred C57BL, Internal medicine, MESH : Mice, Genetics, medicine, Animals, MESH: Receptors, Thyroid Hormone, Muscle, Skeletal, MESH: Electron Transport, Molecular Biology, MESH: Mice, 030304 developmental biology, Insulin-like growth factor 1 receptor, MESH: DNA, Mitochondrial, Skeletal muscle, Hypertrophy, Lipid Metabolism, MESH: Male, Mice, Inbred C57BL, Endocrinology, Mitochondrial biogenesis, MESH: Muscle Fibers, Fast-Twitch, MESH : Muscle Contraction, MESH : Mice, Knockout, MESH : Animals, 030217 neurology & neurosurgery
Abstract: International audience; In vertebrates, skeletal muscle myofibers display different contractile and metabolic properties associated with different mitochondrial content and activity. We have previously identified a mitochondrial triiodothyronine receptor (p43) regulating mitochondrial transcription and mitochondrial biogenesis. When overexpressed in skeletal muscle, it increases mitochondrial DNA content, stimulates mitochondrial respiration, and induces a shift in the metabolic and contractile features of muscle fibers toward a slower and more oxidative phenotype. Here we show that a p43 depletion in mice decreases mitochondrial DNA replication and respiratory chain activity in skeletal muscle in association with the induction of a more glycolytic muscle phenotype and a decrease of capillary density. In addition, p43(-/-) mice displayed a significant increase in muscle mass relative to control animals and had an improved ability to use lipids. Our findings establish that the p43 mitochondrial receptor strongly affects muscle mass and the metabolic and contractile features of myofibers and provides evidence that this receptor mediates, in part, the influence of thyroid hormone in skeletal muscle.
Published: 2012
Full Text: View/download PDF

14. INF2 mutations in Charcot-Marie-Tooth disease with glomerulopathy

Author: Christophe Charasse, Miguel A. Alonso, Rodrick Montjean, Dominique Pouthier, Leila Balafrej, Pierre Ronco, Jacques Dantal, Georges Deschênes, Jean-Michel Vallat, Eric LeGuern, Guillaume Canaud, Alain Bonnardeaux, Anne Guiochon-Mantel, Marie-Josèphe Tête, Olivier Gribouval, Olivia Boyer, Laurence Richard, Christelle Arrondel, Philippe Petiot, Geneviève Benoit, Odile Dubourg, Alexandre Karras, Evelyne Huynh Cong, Isabelle Broutin, Emmanuelle Plaisier, Corinne Antignac, Géraldine Mollet, Claire Pouteil-Noble, Marie-Claire Gubler, Sophie Saunier, Benoît Funalot, Patrice Deteix, Fabien Nevo, Néphropathies héréditaires et rein en développement (UMR_S 983), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de néphrologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Pierre et Marie Curie - Paris 6 (UPMC), Service de Biochimie et Génétique Moléculaire [CHU Limoges], CHU Limoges, Centre de référence national neuropathies périphériques rares [CHU Limoges], Service de Neurologie [CHU Limoges], Service de néphrologie pédiatrique, Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], SARS International Centre for Marine Molecular Biology, Neuropathies héréditaires et rein en développement, Institut National de la Santé et de la Recherche Médicale (INSERM), Equipe Avenir Tour Lavoisier, Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Service de néphrologie et transplantation, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre de Recherche Guy- Bernier, Hôpital Maisonneuve-Rosemont, Service de transplantation et soins intensifs, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], CH de Saint-Brieuc, Service de Néphrologie et Immunologie Clinique, Hôtel Dieu-Centre hospitalier universitaire de Nantes (CHU Nantes), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Université Paris Diderot - Paris 7 (UPD7), CHU Gabriel Montpied [Clermont-Ferrand], CHU Clermont-Ferrand, Institut de Myologie, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Pierre et Marie Curie - Paris 6 (UPMC), Service de neurologie, Hospices Civils de Lyon (HCL)-Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Service de Néphrologie, Centre Hospitalier de Luxembourg [Luxembourg] (CHL), 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), Service de génétique moléculaire, pharmacogénétique et hormonologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Laboratoire de cristallographie et RMN biologiques (LCRB - UMR 8015), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université Paris Descartes - Paris 5 (UPD5), Remodelage et Reparation du Tissu Renal, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centro de Biología Molecular Severo Ochoa [Madrid] (CBMSO), Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Service de Génétique Médicale [CHU Necker], Néphropathies héréditaires et rein en développement ( UMR_S 983 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Necker - Enfants Malades [AP-HP], CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Université Paris Descartes - Paris 5 ( UPD5 ), Service de néphrologie et dialyses, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Université Pierre et Marie Curie - Paris 6 ( UPMC ), Université de Montréal-CHU Sainte Justine [Montréal], Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Hospices Civils de Lyon ( HCL ) -Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], Hôtel Dieu-Centre hospitalier universitaire de Nantes ( CHU Nantes ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré, Université Paris Diderot - Paris 7 ( UPD7 ), CHU Gabriel Montpied ( CHU ), 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)-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 ), Hospices Civils de Lyon ( HCL ) -Hôpital de la Croix-Rousse [CHU - HCL], Centre Hospitalier de Luxembourg, Centre de Référence pour les Epilepsies Rares, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP]-Centre de Référence pour les Epilepsies Rares, Service de Génétique [Pitié-Salpêtrière], Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP], Centre de Recherche de l'Institut du Cerveau et de la Moelle épinière ( CRICM ), 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 ), Université Paris-Sud - Paris 11 ( UP11 ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bicêtre, Laboratoire de cristallographie et RMN biologiques ( LCRB - UMR 8015 ), Université Paris Descartes - Paris 5 ( UPD5 ) -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 ), Centro de Biología Molecular Severo Ochoa ( CBMSO ), Universidad Autonoma de Madrid ( UAM ) -Consejo Superior de Investigaciones Científicas [Spain] ( CSIC ), RONCO, Pierre, 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), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Universidad Autónoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), CHU de Saint-Brieuc, Agence Nationale de la Recherche (France), Association Française contre les Myopathies, Fondation pour la Recherche Médicale, Fonds de la Recherche en Sante du Québec, and Ministerio de Ciencia e Innovación (España)
Subjects: Male, Charcot–Marie–Tooth neuropathy, Pathology, MESH : Actins, MESH : Charcot-Marie-Tooth Disease, urologic and male genital diseases, Mice, Myelin, 0302 clinical medicine, MESH : Child, Charcot-Marie-Tooth Disease, MESH: Child, MESH: Charcot-Marie-Tooth Disease, Medicine, MESH: Animals, Age of Onset, Child, 0303 health sciences, MESH: Middle Aged, Glomerulosclerosis, Focal Segmental, General Medicine, female genital diseases and pregnancy complications, MESH : Age of Onset, 3. Good health, MESH : Phenotype, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Myelin maintenance, MESH: Young Adult, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], MESH: Myelin and Lymphocyte-Associated Proteolipid Proteins, MESH: Proteolipids, MESH : Heterozygote, medicine.medical_specialty, Proteolipids, MESH: Age of Onset, MESH : Young Adult, Formins, MESH: Phenotype, MESH: Actins, 03 medical and health sciences, MESH : Adolescent, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Humans, MESH: Myelin Proteins, MESH : Middle Aged, MESH: Adolescent, MESH: Humans, MESH : Humans, Membrane Transport Proteins, Kidney metabolism, MESH: Adult, medicine.disease, MESH : Glomerulosclerosis, Focal Segmental, INF2, Endocrinology, Mutation, MESH: Schwann Cells, MESH: Female, 030217 neurology & neurosurgery, Kidney, MESH: Membrane Transport Proteins, Glomerulosclerosis, Focal segmental glomerulosclerosis, MESH : Membrane Transport Proteins, Peripheral myelin protein 22, MESH : Myelin and Lymphocyte-Associated Proteolipid Proteins, MESH : Female, MESH: Heterozygote, Myelin and Lymphocyte-Associated Proteolipid Proteins, Microfilament Proteins, Middle Aged, MESH : Adult, MESH : Kidney, Phenotype, medicine.anatomical_structure, Female, MESH : Mutation, Myelin Proteins, Adult, Heterozygote, MESH: Mutation, Adolescent, MESH : Microfilament Proteins, MESH: Glomerulosclerosis, Focal Segmental, MESH : Male, MESH : Schwann Cells, MESH : Myelin Proteins, Young Adult, MESH: Microfilament Proteins, Glomerulopathy, Internal medicine, MESH : Mice, Animals, MESH: Mice, 030304 developmental biology, urogenital system, business.industry, Myelin protein zero, MESH: Kidney, Actins, MESH: Male, MESH : Proteolipids, Schwann Cells, MESH : Animals, business
Abstract: Backgrounds: Charcot–Marie–Tooth neuropathy has been reported to be associated with renal diseases, mostly focal segmental glomerulosclerosis (FSGS). However, the common mechanisms underlying the neuropathy and FSGS remain unknown. Mutations in INF2 were recently identified in patients with autosomal dominant FSGS. INF2 encodes a formin protein that interacts with the Rho-GTPase CDC42 and myelin and lymphocyte protein (MAL) that are implicated in essential steps of myelination and myelin maintenance. We therefore hypothesized that INF2 may be responsible for cases of Charcot–Marie–Tooth neuropathy associated with FSGS., Methods: We performed direct genotyping of INF2 in 16 index patients with Charcot–Marie–Tooth neuropathy and FSGS who did not have a mutation in PMP22 or MPZ, encoding peripheral myelin protein 22 and myelin protein zero, respectively. Histologic and functional studies were also conducted., Methods: We identified nine new heterozygous mutations in 12 of the 16 index patients (75%), all located in exons 2 and 3, encoding the diaphanous-inhibitory domain of INF2. Patients presented with an intermediate form of Charcot–Marie–Tooth neuropathy as well as a glomerulopathy with FSGS on kidney biopsy. Immunohistochemical analysis revealed strong INF2 expression in Schwann-cell cytoplasm and podocytes. Moreover, we demonstrated that INF2 colocalizes and interacts with MAL in Schwann cells. The INF2 mutants perturbed the INF2–MAL–CDC42 pathway, resulting in cytoskeleton disorganization, enhanced INF2 binding to CDC42 and mislocalization of INF2, MAL, and CDC42., Conclusions: INF2 mutations appear to cause many cases of FSGS-associated Charcot–Marie–Tooth neuropathy, showing that INF2 is involved in a disease affecting both the kidney glomerulus and the peripheral nervous system. These findings provide new insights into the pathophysiological mechanisms linking formin proteins to podocyte and Schwann-cell function., Funded by the Agence Nationale de la Recherche and others.Supported by grants from the Association pour l'Utilisation du Rein Artificiel (to Dr. Antignac), Association Française contre les Myopathies (ANR-08-GENOPAT-017-01, to Dr. Antignac), Agence Nationale de la Recherche (PodoNet project number ANR-07-E-RARE-011-01 in the ERA-Net Consortium [JTC2007], to Dr. Antignac, and ANR-06-MRAR-024-01, to Dr. Leguern), Fondation pour la Recherche Médicale (project number DMP 2010-11-20-386, to Dr. Antignac, and doctoral funding, to Dr. Boyer), Association des Malades du Syndrome Néphrotique (to Dr. Mollet), Fonds de la Recherche en Santé du Québec (Fellowship Training Award to Dr. Benoit), and Ministerio de Ciencia e Innovación (BFU2009-07886 and CONSOLIDER COAT CSD2009-00016, to Dr. Alonso).
Published: 2011
Full Text: View/download PDF

15. PTPN22 R620W genotype-phenotype correlation analysis and gene-environment interaction study in early rheumatoid arthritis: results from the ESPOIR cohort

Author: Salliot, Carine, Dawidowicz, Karen, Lukas, Cédric, Guedj, Mickael, Paccard, Caroline, Benessiano, Joelle, Dougados, Maxime, Nicaise, Pascale, Meyer, Olivier, Dieudé, Phillippe, Saraux, Alain, Hôpital Lariboisière, 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), Département de Rhumatologie[Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, 'Cartes d'Identité des Tumeurs ' program (CIT), Ligue Nationale Contre le Cancer, Department of Biostatistics, Pharnext, privé, CIC - CHU Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service Rhumatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Merck Sharp, Dohme (MSD), INSERM, French Society of Rheumatology, Abbott, Wyeth, Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Lariboisière - Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier) - Hôpital Lapeyronie, Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) - AP-HP - Hôpital Bichat - Claude Bernard [Paris] - Université Paris Diderot - Paris 7 (UPD7), Université de Brest (UBO) - IFR148, Université de Brest (UBO) - Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7)
Subjects: Oncology, Male, [SDV]Life Sciences [q-bio], SHARED EPITOPE ALLELES, MESH : Genotype, PROGRESSION, Logistic regression, Arthritis, Rheumatoid, Cohort Studies, MESH: Genotype, 0302 clinical medicine, Risk Factors, MESH : Peptides, Cyclic, MESH: Risk Factors, Pharmacology (medical), MESH : Female, 030212 general & internal medicine, Gene–environment interaction, MESH: Protein Tyrosine Phosphatase, Non-Receptor Type 22, MESH: Cohort Studies, MESH: Arthritis, Rheumatoid, MESH : Estrogen Replacement Therapy, MESH: Middle Aged, MESH: Polymorphism, Single Nucleotide, Confounding, Estrogen Replacement Therapy, MESH : Polymorphism, Single Nucleotide, Smoking, Absolute risk reduction, Cohort, MESH: Genetic Predisposition to Disease, ASSOCIATION, Middle Aged, MESH : Risk Factors, MESH : Environment, 3. Good health, MESH : Rheumatoid Factor, [SDV] Life Sciences [q-bio], MESH : Phenotype, Phenotype, HLA-DRB1, Rheumatoid arthritis, Female, REPLACEMENT, medicine.medical_specialty, MESH: Rheumatoid Factor, Genotype, MESH : Male, MESH : Cohort Studies, Environment, CAUCASIAN POPULATION, MESH: Phenotype, Peptides, Cyclic, Polymorphism, Single Nucleotide, PTPN22, 03 medical and health sciences, Rheumatology, Rheumatoid Factor, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, MESH : Middle Aged, Hormonal treatments, MESH: Environment, METAANALYSIS, MESH: Peptides, Cyclic, 030203 arthritis & rheumatology, MESH: Humans, business.industry, Early RA, MESH : Humans, MESH: Biological Markers, Protein Tyrosine Phosphatase, Non-Receptor Type 22, Odds ratio, medicine.disease, MESH: Estrogen Replacement Therapy, POLYMORPHISM, MESH: Male, MESH : Biological Markers, PTPN22 620W, MESH : Protein Tyrosine Phosphatase, Non-Receptor Type 22, Immunology, MESH : Arthritis, Rheumatoid, RISK, MESH : Genetic Predisposition to Disease, CIGARETTE-SMOKING, business, MESH: Female, Biomarkers
Abstract: International audience; OBJECTIVES: To investigate genotype-phenotype correlation and gene-environment interaction between PTPN22 R620W environmental factors such as tobacco/hormonal treatments in an inception cohort of RA patients. METHODS: An intra-cohort study including 532 Caucasian RA patients genotyped for the PTPN22 rs2476601 polymorphism was performed. Anti-CCP and RF status at baseline, presence of bone erosions at 1 year, HLADR1 and/or DR4 status, demography, comorbidities, exposure to tobacco with the cumulative dose in pack-years, hormonal treatments and treatments received for RA were collected. Logistic regression was performed to estimate the ORs and multiplicative interaction with adjustment for confounding factors. Gene-environment interaction was estimated by the relative excess risk due to interaction (RERI), attributable proportion (AP) and synergy index (SI). RESULTS: PTPN22 620W risk allele was associated with ACPA production [odds ratio (OR) = 2.21, 95% CI 1.4, 3.4, P
Published: 2011
Full Text: View/download PDF

16. HLA-B27 positive patients differ from HLA-B27 negative patients in clinical presentation and imaging: results from the DESIR cohort of patients with recent onset axial spondyloarthritis

Author: Chung, Ho Yin, Machado, Pedro, Van Der Heijde, Désirée, D'Agostino, Maria-Antonietta, Dougados, Maxime, Saraux, Alain, Department of Rheumatology, University Hospital Maastricht, Service de Rhumatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Service de rhumatologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie et Pathologie (EA2216), Université de Brest (UBO)-IFR148, Centre d'Investigation Clinique (CIC - Brest), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Ambroise Paré, Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Cochin [AP-HP], Université de Brest (UBO) - IFR148, and Université de Brest (UBO) - Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Settore MED/16 - REUMATOLOGIA, Delayed Diagnosis, Spondyloarthropathy, [SDV]Life Sciences [q-bio], MESH : Sacroiliac Joint, MESH: Epidemiologic Methods, Gastroenterology, Severity of Illness Index, MESH: Magnetic Resonance Imaging, 0302 clinical medicine, MESH : Back Pain, Back pain, Immunology and Allergy, MESH : Female, 030212 general & internal medicine, Age of Onset, MESH: Sacroiliac Joint, Axis, Cervical Vertebra, HLA-B27 Antigen, Sacroiliac joint, MESH : Prognosis, MESH: Middle Aged, MESH : Spondylarthritis, MESH : Adult, Middle Aged, Prognosis, Magnetic Resonance Imaging, 3. Good health, MESH : Age of Onset, [SDV] Life Sciences [q-bio], MESH : Phenotype, Cervical Vertebra, medicine.anatomical_structure, Phenotype, MESH: Young Adult, MESH : Severity of Illness Index, Female, medicine.symptom, Axis, musculoskeletal diseases, Adult, medicine.medical_specialty, MESH : Male, MESH: Age of Onset, MESH: Spondylarthritis, Immunology, MESH : Delayed Diagnosis, MESH : HLA-B27 Antigen, MESH : Young Adult, MESH: Phenotype, General Biochemistry, Genetics and Molecular Biology, MESH : Epidemiologic Methods, MESH: Prognosis, 03 medical and health sciences, Young Adult, Rheumatology, Internal medicine, MESH : Magnetic Resonance Imaging, MESH: Severity of Illness Index, Spondylarthritis, medicine, MESH : Sacroiliitis, Humans, MESH : Middle Aged, Sacroiliitis, MESH: Sacroiliitis, 030203 arthritis & rheumatology, Ankylosing spondylitis, HLA-B27, MESH: Humans, MESH : Axis, business.industry, MESH : Humans, MESH: Biological Markers, MESH: Adult, Sacroiliac Joint, medicine.disease, MESH: Male, Surgery, MESH : Biological Markers, MESH: Delayed Diagnosis, Back Pain, MESH: Back Pain, Age of onset, business, MESH: HLA-B27 Antigen, Epidemiologic Methods, MESH: Female, Biomarkers, MESH: Axis
Abstract: International audience; OBJECTIVE: To clarify the influence of human leucocyte antigen B27 (HLA-B27) status on the phenotype of early axial spondyloarthritis (SpA). METHODS: 708 patients with inflammatory back pain (IBP) defined by Calin or Berlin criteria were recruited; 654 fulfilled at least one of the SpA criteria (modified New York, European Spondyloarthropathy Study Group, Amor or Assessment of SpondyloArthritis international Society classification criteria for axial SpA) and were included in the analyses. Clinical, demographic and imaging parameters were compared between HLA-B27 positive and negative groups. Significant parameters in univariate differences between HLA-B27 positive and negative groups were retested in multivariate models explaining various outcomes. RESULTS: Patients had a short duration of axial symptoms (mean 1.5 years) and HLA-B27 was present in 61.5%. In multivariate analysis, HLA-B27 positivity was associated with a younger age at onset of IBP (regression coefficient (B)=(-2.60), p
Published: 2011
Full Text: View/download PDF

17. Asthma control assessed in the EGEA epidemiological survey and health-related quality of life

Author: Nicole Le Moual, Jocelyne Just, Valérie Siroux, Isabelle Pin, Pierre Scheinmann, Daniel Vervloet, Jean Bousquet, Rachel Nadif, Bénédicte Leynaert, Francine Kauffmann, Lucile Vignoud, Anne Boudier, Josep M. Antó, Christophe Pison, Frédéric Gormand, Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF) - CHU Grenoble - EFS - Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ) - Université Paris-Sud - Paris 11 (UP11) - Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Paul Brousse - Institut National de la Santé et de la Recherche Médicale (INSERM), Département pneumologie et addictologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier) - Hôpital Arnaud de Villeneuve, Service de pneumologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL) - Hospices Civils de Lyon (HCL), Centre de l'asthme et de l'allergologie, Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Trousseau [APHP], Physiopathologie et Epidemiologie de l'Insuffisance Respiratoire, Université Paris Diderot - Paris 7 (UPD7) - Institut National de la Santé et de la Recherche Médicale (INSERM), Clinique de pneumologie, CHU Grenoble, Service de Pneumologie Allergologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) - CHU Necker - Enfants Malades [AP-HP], Service de Pneumologie [Grenoble], CHU Grenoble - Hôpital Michallon, CIBER en Epidemiologia y Salud Pública, Center for Research in Environmental Epidemiology (CREAL), Universitat Pompeu Fabra [Barcelona] - Catalunya ministerio de salud, IMIM-Hospital del Mar, Generalitat de Catalunya, Département de pédiatrie, The EGEA study was supported in part by grants from Merck Sharp & Dohme (MSD), Hospital program of clinical research (PHRC)-Paris, National Research Agency - Health environment, healthwork program, National Research Agency (ANR)- Biological collections for health program, French Agency of health safety, environment and work (AFSSET), the national scientific committee of the medico-technology support at home (AGIR à dom) and the Isere committee against respiratory diseases (COMARES)., Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Grenoble-Hôpital Michallon, Universitat Pompeu Fabra [Barcelona] (UPF)-Catalunya ministerio de salud, Nadif, Rachel, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, MESH: Asthma, Epidemiology, Health-related quality of life, 0302 clinical medicine, Quality of life, Tabaquisme, immune system diseases, Asthma control, Health Status Indicators, MESH : Female, 030212 general & internal medicine, Lung function, MESH: Middle Aged, MESH : Psychometrics, MESH: Immunoglobulin E, Smoking, MESH : Adult, Middle Aged, MESH: Case-Control Studies, humanities, 3. Good health, MESH : Smoking, MESH : Phenotype, Phenotype, Asthma control steps, Female, France, MESH : Health Status Indicators, Pulmonary and Respiratory Medicine, Adult, medicine.medical_specialty, MESH: Smoking, MESH : Case-Control Studies, Psychometrics, Health-relatedquality of life, MESH : Male, MESH: Phenotype, MESH : Asthma, MESH : Immunoglobulin E, 03 medical and health sciences, MESH: Psychometrics, MESH: Health Status Indicators, medicine, Humans, MESH : Middle Aged, MESH : France, Asthma, Health related quality of life, MESH: Humans, business.industry, MESH : Humans, Asma -- Epidemiologia, MESH: Quality of Life, MESH: Adult, MESH : Quality of Life, Immunoglobulin E, medicine.disease, MESH: Male, Uncontrolled asthma, respiratory tract diseases, MESH: France, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, Physical therapy, Quality of Life, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female
Abstract: International audience; BACKGROUND: The aims were to assess 1) the relationship of asthma control assessed by combining epidemiological survey questions and lung function to Health-Related Quality of Life (HRQL) and 2) whether individuals with controlled asthma reach similar generic HRQL levels as individuals without asthma. METHODS: The analysis included 584 individuals without asthma and 498 with asthma who participated in the follow-up of the Epidemiological study on Genetics and Environment of Asthma (EGEA). Asthma control was assessed from survey questions and lung function, closely adapted from the 2006-2009 Global Initiative for Asthma guidelines. The Asthma Quality of Life Questionnaire (AQLQ, scores range:1-7) and the generic SF-36 (scores range: 0-100) were used. RESULTS: Adjusted mean total AQLQ score decreased by 0.5 points for each asthma control steps (6.4, 5.9 and 5.4 for controlled, partly-controlled and uncontrolled asthma respectively, p < 0.0001). The differences in SF-36 scores between individuals with controlled asthma and those without asthma were minor and not significant for the PCS (-1, p = 0.09), borderline significant for the MCS (-1.6, p = 0.05) and small for the 8 domains (
Published: 2011
Full Text: View/download PDF

18. Trade-off between bile resistance and nutritional competence drives Escherichia coli diversification in the mouse gut

Author: Nadine Cerf-Bensussan, Dominique Rainteau, François Taddei, Sabine Rakotobe, Marianne De Paepe, Valérie Gaboriau-Routhiau, Interactions de l'épithelium intestinal et du système immunitaire (UMR_S 793), Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Inflammation intestinale, 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), Robustesse et évolvabilité de la vie (U1001), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), MDP was supported by the Fondation pour la Recherche Médicale (http://www.frm.org/)., 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)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Recherche Agronomique (INRA), Interactions de l'épithelium intestinal et du système immunitaire ( UMR_S 793 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Recherche Agronomique ( INRA ), MICrobiologie de l'ALImentation au Service de la Santé humaine ( MICALIS ), Institut National de la Recherche Agronomique ( INRA ) -AgroParisTech, 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 ), Robustesse et évolvabilité de la vie ( U1001 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), and Autard, Delphine
Subjects: Operon, Mutant, Genetic Fitness, MESH: Escherichia coli Proteins, Mice, MESH : Selection, Genetic, MESH: Animals, 0303 health sciences, MESH : Trans-Activators, MESH: Escherichia coli, Escherichia coli Proteins, Microbiology and Parasitology, Bacterial, SDV:GEN, MESH: Transcription Factors, MESH : Multienzyme Complexes, Microbiologie et Parasitologie, MESH : Phenotype, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Animals, Bacterial Outer Membrane Proteins, Bile Acids and Salts, Biodiversity, DNA-Binding Proteins, Escherichia coli, Flagella, Gastrointestinal Tract, Gene Expression Regulation, Immunity, Innate, Multienzyme Complexes, Mutation, Nutritional Physiological Phenomena, Phenotype, Selection, Genetic, Trans-Activators, Transcription Factors, MESH : DNA-Binding Proteins, MESH : Gene Expression Regulation, Bacterial, MESH: Phenotype, Microbiology, MESH: Flagella, MESH: Biodiversity, 03 medical and health sciences, Genetics, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Molecular Biology, Biology, Ecology, Evolution, Behavior and Systematics, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH : Genetic Fitness, 030306 microbiology, MESH: Bacterial Outer Membrane Proteins, Immunity, Innate, Colonisation, Regulon, MESH : Nutritional Physiological Phenomena, MESH: Gastrointestinal Tract, MESH : Gastrointestinal Tract, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, Cancer Research, MESH : Escherichia coli, MESH : Transcription Factors, MESH: Selection, Genetic, [SDV.GEN] Life Sciences [q-bio]/Genetics, Gut flora, medicine.disease_cause, MESH: Multienzyme Complexes, MESH: Genetic Fitness, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, MESH : Biodiversity, Genetics (clinical), 2. Zero hunger, Experimental evolution, MESH: Gene Expression Regulation, Bacterial, biology, MESH : Escherichia coli Proteins, MESH : Immunity, Innate, MESH: Immunity, Innate, MESH : Mutation, Research Article, MESH: Mutation, lcsh:QH426-470, MESH: Trans-Activators, MESH: Bile Acids and Salts, Model Organisms, MESH : Mice, medicine, Selection, Genetic, MESH: Nutritional Physiological Phenomena, MESH : Bacterial Outer Membrane Proteins, MESH: Mice, 030304 developmental biology, Evolutionary Biology, Gene Expression Regulation, Bacterial, biology.organism_classification, MESH : Bile Acids and Salts, lcsh:Genetics, bacteria, MESH : Animals, MESH : Flagella, MESH: DNA-Binding Proteins
Abstract: Bacterial diversification is often observed, but underlying mechanisms are difficult to disentangle and remain generally unknown. Moreover, controlled diversification experiments in ecologically relevant environments are lacking. We studied bacterial diversification in the mammalian gut, one of the most complex bacterial environments, where usually hundreds of species and thousands of bacterial strains stably coexist. Herein we show rapid genetic diversification of an Escherichia coli strain upon colonisation of previously germ-free mice. In addition to the previously described mutations in the EnvZ/OmpR operon, we describe the rapid and systematic selection of mutations in the flagellar flhDC operon and in malT, the transcriptional activator of the maltose regulon. Moreover, within each mouse, the three mutant types coexisted at different levels after one month of colonisation. By combining in vivo studies and determination of the fitness advantages of the selected mutations in controlled in vitro experiments, we provide evidence that the selective forces that drive E. coli diversification in the mouse gut are the presence of bile salts and competition for nutrients. Altogether our results indicate that a trade-off between stress resistance and nutritional competence generates sympatric diversification of the gut microbiota. These results illustrate how experimental evolution in natural environments enables identification of both the selective pressures that organisms face in their natural environment and the diversification mechanisms., Author Summary The mechanisms generating the huge biodiversity on earth are not entirely understood. Bacterial populations are powerful models to explore the mechanisms of evolution, owing to their big population size, rapid growth, and high mutation rate. One of the more complex bacterial community is the mammalian gut microbiota, and Escherichia coli is one of the first colonizers of the newborn intestine. Herein we studied diversification of an Escherichia coli strain in germ-free mice, a simplified though ecologically relevant system. We show rapid genetic diversification upon colonization, characterized by the systematic selection of mutations in three different pathways: in the global regulator EnvZ/OmpR controlling outer membrane permeability, in the flagellar operon, and in the maltose regulon. By combining in vivo and in vitro experiments, we show that the selective forces that drive E. coli diversification are the presence of bile salts and the competition for nutrients. Altogether our results indicate that a trade-off between stress resistance and nutritional competence is sufficient to mediate diversification of bacteria. These results illustrate how experimental evolution in natural environments allows the identification of the selective pressures that organisms face in their natural environment, as well as the diversification mechanisms.
Published: 2011
Full Text: View/download PDF

19. Mutations in the TGFβ binding-protein-like domain 5 of FBN1 are responsible for acromicric and geleophysic dysplasias

Author: Angela F. Brady, Louise Zylberberg, Yasemin Alanay, Gwenaëlle Collod-Béroud, Andrea Superti-Furga, Sally Ann Lynch, Michel Polak, Avinash Abhyankar, André Mégarbané, Martine Le Merrer, Suneel S. Apte, Marie-Pierre Cordier, Carine Le Goff, Arnold Munnich, Clémentine Mahaut, David Sillence, Sacha A. Jensen, Pelin Özlem Şimşek Kiper, Christine Bole-Feysot, Lauren W. Wang, David L. Rimoin, Vicken Topouchian, Patrick Nitschke, Slimane Allali, Koenraad Devriendt, Penny A. Handford, Catherine Boileau, Sylvie Odent, Deborah Krakow, Irene Stolte-Dijkstra, Damien Bonnet, Geert Mortier, Valérie Cormier-Daire, Sheila Unger, Jean-Laurent Casanova, Bernhard Zabel, Marianne Rohrbach, Hiroshi Kitoh, David Geneviève, Çocuk Sağlığı ve Hastalıkları, Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller University [New York], Department of Biochemistry [Oxford], University of Oxford, Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), 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), Service de cardiologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Department of Pediatrics, Hacettepe University = Hacettepe Üniversitesi, Service de cytogénétique constitutionnelle, Hospices Civils de Lyon (HCL)-CHU de Lyon-Centre Neuroscience et Recherche, Institute of Child Health, Service de génétique médicale [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Department of Orthopaedic Surgery, Nagoya University, Department of Molecular Cellular and Developmental Biology, University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC)-Howard Hughes Medical Institute (HHMI), Our Lady's hospital for Sick Children, Our Lady's Hospital for Sick Children, Unité de génétique médicale, Université Saint-Joseph de Beyrouth (USJ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Medical Genetics, Universiteit Gent = Ghent University (UGENT), hôpital Sud, Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Clinical Genetics, Academic Department of Medical Genetics, Westmead Hospital [Sydney], Department of Clinical Genetics, Service de Pédiatrie, Université de Lausanne = University of Lausanne (UNIL), Service de chirurgie orthopédique pédiatrique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Service de Génétique humaine, Centre for Pediatrics and Adolescent Medicine, University of Freiburg [Freiburg]-University Hospital Freiburg, Endocrinologie moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM), Plate Forme Paris Descartes de Bioinformatique (BIP-D), Université Paris Descartes - Paris 5 (UPD5), Génétique Humaine des Maladies Infectieuses (Inserm U980), Service de cardiologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), COLLOD-BEROUD, Gwenaëlle, Department of Biomedical Engineering, Cleveland Clinic-Lerner Research Institute, University of Oxford [Oxford], Institut des Sciences de la Terre de Paris (iSTeP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Centre de Référence Malformations Cardiaques Congénitales Complexes, North West Thames Regional Genetics, Northwick Park Hospital, Service de Génétique, Hospices Civils de Lyon (HCL), Center for Human Genetics, Université Catholique de Louvain (UCL)-Cliniques Universitaires Saint-Luc [Bruxelles], Cellules souches mésenchymateuses, environnement articulaire et immunothérapies de la polyarthrite rhumatoide, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), Departments of Orthopedic Surgery and Human Genetics, University of California-University of California, National Centre for Medical Genetics, Antwerp University Hospital [Edegem] (UZA), Service de Génétique Clinique, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Sud, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Centre National de la Recherche Scientifique (CNRS), service d'endocrinologie, gynécologie, diabétologie, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Division of Metabolism, University Children's Hospital, Clinical genetics, University Medical Center Groningen [Groningen] (UMCG), Université de Lausanne (UNIL), Medical Genetics Institute, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Bioinformatique, Service de biochimie, d'hormonologie et de génétique moléculaire [CHU Amrboise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Ambroise Paré [AP-HP], Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de recherche génomique et physiologie de la lactation (GPL), Institut National de la Recherche Agronomique (INRA), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of California-University of California-Howard Hughes Medical Institute (HHMI), Universiteit Gent = Ghent University [Belgium] (UGENT), Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Génomique et Physiologie de la Lactation (GPL), Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, St. Giles Laboratory of Human Genetics of Infectious Diseases, Rockefeller Branch, rockefeller university, Ghent University [Belgium] (UGENT), Hôpital Sud, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Cleveland Clinic Foundation-Lerner Research Institute, St Giles laboratory of Human Genetics and Infectious Diseases, Institut des Sciences de la Terre de Paris ( iSTeP ), Centre National de la Recherche Scientifique ( CNRS ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques, Université Montpellier 1 ( UM1 ) -IFR3-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Hospices Civils de Lyon ( HCL ), Université Catholique de Louvain ( UCL ) -Cliniques Universitaires Saint-Luc [Bruxelles], Université Montpellier 1 ( UM1 ) -IFR3-Institut National de la Santé et de la Recherche Médicale ( INSERM ), University of California at Los Angeles [Los Angeles] ( UCLA ), Université Saint-Joseph de Beyrouth ( USJ ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), University Hospital Antwerp, Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Sud, Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140-Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -CHU Necker - Enfants Malades [AP-HP], The Children's Hospital at Westmead, University Medical Center Groningen, Université de Lausanne ( UNIL ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Université Paris Descartes - Paris 5 ( UPD5 ), Génétique Humaine des Maladies Infectieuses ( Inserm U980 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Service de biochimie, d'hormonologie et de génétique moléculaire, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, Hémostase, bio-ingénierie et remodelage cardiovasculaires ( LBPC ), Université Paris 13 ( UP13 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Galilée, University of Zurich, and Cormier-Daire, V
Subjects: MESH: Extracellular Matrix Proteins, DNA Mutational Analysis, Fluorescent Antibody Technique, Marfan Syndrome, MESH : Dwarfism, MESH: Protein Structure, Tertiary, Arachnodactyly, 0302 clinical medicine, MESH : Child, MESH: Child, Acromicric dysplasia, Genetics(clinical), Eye Abnormalities, MESH: DNA Mutational Analysis, MESH: Dwarfism, Child, MESH: Fluorescent Antibody Technique, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Exome sequencing, Genetics & Heredity, Inclusion Bodies, 0303 health sciences, Mutation, Extracellular Matrix Proteins, MESH: Middle Aged, 3. Good health, MESH : Connective Tissue, MESH : Phenotype, MESH: Young Adult, Child, Preschool, MESH : Protein Structure, Tertiary, musculoskeletal diseases, MESH : Heterozygote, MESH: Connective Tissue, MESH : Young Adult, Limb Deformities, Congenital, Dwarfism, MESH : DNA Mutational Analysis, MESH: Phenotype, Fibrillins, Article, 03 medical and health sciences, 1311 Genetics, MESH : Adolescent, Genetics, Humans, MESH : Middle Aged, MESH: Adolescent, MESH: Bone Diseases, Developmental, [SDV.GEN]Life Sciences [q-bio]/Genetics, Bone Diseases, Developmental, MESH : Bone Diseases, Developmental, MESH: Humans, MESH : Humans, MESH: Child, Preschool, MESH: Adult, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, Protein Structure, Tertiary, MESH : Microfibrils, MESH : Fluorescent Antibody Technique, Human medicine, MESH : Transforming Growth Factor beta1, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, 030217 neurology & neurosurgery, MESH: Signal Transduction, Candidate gene, Fibrillin-1, MESH : Child, Preschool, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease_cause, MESH: Transforming Growth Factor beta1, MESH : Exons, Genetics (clinical), MESH: Heterozygote, Microfilament Proteins, Exons, MESH : Adult, Middle Aged, MESH: Eye Abnormalities, Weill–Marchesani syndrome, MESH: Microfibrils, Phenotype, Connective Tissue, MESH : Mutation, medicine.symptom, Fibrillin, Signal Transduction, MESH : Limb Deformities, Congenital, Adult, 2716 Genetics (clinical), congenital, hereditary, and neonatal diseases and abnormalities, Heterozygote, MESH: Limb Deformities, Congenital, MESH: Mutation, MESH : Microfilament Proteins, Adolescent, 610 Medicine & health, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Biology, Short stature, MESH: Marfan Syndrome, Transforming Growth Factor beta1, MESH: Microfilament Proteins, Young Adult, MESH : Extracellular Matrix Proteins, MESH : Eye Abnormalities, medicine, [ SDV.BDD ] Life Sciences [q-bio]/Development Biology, 030304 developmental biology, MESH : Signal Transduction, MESH : Marfan Syndrome, MESH: Inclusion Bodies, GENE, MESH : Inclusion Bodies, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, 10036 Medical Clinic, Microfibrils, MESH: Exons, MATRIX
Abstract: International audience; Geleophysic (GD) and acromicric dysplasia (AD) belong to the acromelic dysplasia group and are both characterized by severe short stature, short extremities, and stiff joints. Although AD has an unknown molecular basis, we have previously identified ADAMTSL2 mutations in a subset of GD patients. After exome sequencing in GD and AD cases, we selected fibrillin 1 (FBN1) as a candidate gene, even though mutations in this gene have been described in Marfan syndrome, which is characterized by tall stature and arachnodactyly. We identified 16 heterozygous FBN1 mutations that are all located in exons 41 and 42 and encode TGFb-binding protein-like domain 5 (TB5) of FBN1 in 29 GD and AD cases. Microfibrillar network disorganization and enhanced TGFb signaling were consistent features in GD and AD fibro-blasts. Importantly, a direct interaction between ADAMTSL2 and FBN1 was demonstrated, suggesting a disruption of this interaction as the underlying mechanism of GD and AD phenotypes. Although enhanced TGFb signaling caused by FBN1 mutations can trigger either Marfan syndrome or GD and AD, our findings support the fact that TB5 mutations in FBN1 are responsible for short stature phenotypes.
Published: 2011
Full Text: View/download PDF

20. Phenotyping the claudin 11 deficiency in testis: from histology to immunohistochemistry

Author: Brigitte Le Magueresse-Battistoni, Alexander Gow, Séverine Mazaud-Guittot, Groupe d'Etude de la Reproduction Chez l'Homme et les Mammiferes (GERHM), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), NIDCD NIH HHS DC006262 R01 DC006262, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Groupe d'Etude de la Reproduction Chez l'Homme et les Mammiferes ( GERHM ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Cardiovasculaire, métabolisme, diabétologie et nutrition ( CarMeN ), Institut National de la Recherche Agronomique ( INRA ) -Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon ( INSA Lyon ), and Université de Lyon-Institut National des Sciences Appliquées ( INSA ) -Institut National des Sciences Appliquées ( INSA ) -Hospices Civils de Lyon ( HCL ) -Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: Male, Somatic cell, MESH: Spermatogonia, MESH : Immunohistochemistry, MESH : Eosine Yellowish-(YS), MESH: Formaldehyde, MESH: Mice, Knockout, MESH: Spermatocytes, MESH: Tight Junctions, Mice, MESH : Spermatogonia, 0302 clinical medicine, Spermatocytes, MESH : Fixatives, MESH : Microscopy, MESH: Animals, MESH: Fixatives, MESH: Nerve Tissue Proteins, Hematoxylin, MESH : Nerve Tissue Proteins, Blood–testis barrier, Mice, Knockout, 0303 health sciences, Microscopy, Claudin 11, 030219 obstetrics & reproductive medicine, Seminiferous Tubules, Sertoli cell, Immunohistochemistry, Cell biology, MESH : Spermatocytes, MESH : Phenotype, medicine.anatomical_structure, Phenotype, Seminiferous Epithelium, MESH : Seminiferous Tubules, MESH : Seminiferous Epithelium, Eosine Yellowish-(YS), Germ cell, MESH : Sertoli Cells, medicine.medical_specialty, Cell type, endocrine system, sertoli cell, MESH: Citric Acid, MESH: Microscopy, MESH : Infertility, MESH : Male, MESH: Seminiferous Tubules, Nerve Tissue Proteins, MESH : Citric Acid, blood testis barrier, Biology, MESH: Phenotype, Citric Acid, Article, Tight Junctions, 03 medical and health sciences, Fixatives, MESH: Sertoli Cells, Internal medicine, Formaldehyde, MESH : Mice, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Infertility, Claudin, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, 030304 developmental biology, MESH : Hematoxylin, MESH : Tight Junctions, Sertoli Cells, MESH: Immunohistochemistry, Epithelium, Spermatogonia, spermatogenesis, MESH: Male, Endocrinology, Infertility, MESH : Formaldehyde, Claudins, MESH : Mice, Knockout, MESH: Eosine Yellowish-(YS), MESH: Hematoxylin, MESH : Animals, gene regulation, Spermatogenesis, MESH: Seminiferous Epithelium
Abstract: International audience; The testis is a heterogeneous organ that comprises a number of cell types, including germ cells at -different stages in their maturation, differentiated neighbor nursing cells, and endocrine somatic cells. Despite such cellular heterogeneity the testis is highly organized, with germ cell development and differentiation being compartmentalized into the interconnected tubular network of the seminiferous epithelium. Intratesticular scaffolds rely heavily on the basement membrane of the seminiferous tubules while germ cell development inside the seminiferous epithelium is critically dependent on the Blood Testis Barrier (BTB). The BTB is a macromolecular tight junction complex generated by somatic Sertoli cells within the seminiferous epithelium. The BTB divides the seminiferous epithelium into two compartments: the basal compartment, which delineates a niche for the proliferation and renewal of spermatogonia; and the adluminal compartment, where differentiating germ cells undergo meiosis and spermiogenesis. The BTB is unique in mammalian tissues because it is cyclically reconstructed during the spermatogenic cycle as preleptotene spermatocytes migrate from the basal compartment to the adluminal compartment and enter meiosis. In mouse, the loss of the BTB in the absence of the claudin 11 protein causes azoospermia and leads to infertility. Specifically, cldn11 deficiency results in sloughing of the cells of the seminiferous epithelium into the lumen. Understanding this pathophysiology has involved histological examination of the tissue defects as well as immunohistological characterization. Here, we present a comparative study of several modifications to the classical Hematoxylin-Eosin stain that may improve the diagnostic usefulness of this technique, as well as the use of several selective markers to identify testicular cell types.
Published: 2011
Full Text: View/download PDF

21. Genotype-phenotype correlations of TGFBI p.Leu509Pro, p.Leu509Arg, p.Val613Gly, and the allelic association of p.Met502Val-p.Arg555Gln mutations

Author: Niel-Butschi F, Kantelip B, Iwaszkiewicz J, Zoete V, Boimard M, Delpech M, Jl, Bourges, Renard G, D'Hermies F, Pj, Pisella, Hamel C, Delbosc B, Sophie Valleix, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Laboratoire d'anatomie pathologique [Besancon], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz-Université de Franche-Comté ( UFC ), Hôtel-Dieu, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôtel-Dieu-Université Paris Descartes - Paris 5 ( UPD5 ), Centre de référence des affections sensorielles d'origine génétique, Centre Hospitalier Régional Universitaire [Montpellier] ( CHRU Montpellier ) -Hôpital Gui De Chaulliac, Service d'ophtalmologie [Besançon], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Laboratoire de Biochimie et Génétique Moléculaire, Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service d'Anatomie pathologique [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôtel-Dieu-Université Paris Descartes - Paris 5 (UPD5), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui De Chaulliac, Service d'ophtalmologie [CHRU Besançon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Viala, Pascale, Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz-Université de Franche-Comté (UFC), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôtel-Dieu-Université Paris Descartes - Paris 5 (UPD5), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Hôpital Jean Minjoz, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Descartes - Paris 5 (UPD5), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) ( CEF2P / CARCINO ), and Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté [COMUE] ( UBFC ) -Université de Franche-Comté ( UFC )
Subjects: Male, Models, Molecular, MESH: Extracellular Matrix Proteins, MESH : Molecular Sequence Data, MESH : Algeria, Genetic Linkage, MESH : Genotype, MESH: Amino Acid Sequence, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, MESH: Genotype, MESH: Aged, 80 and over, Gene Frequency, Transforming Growth Factor beta, MESH : Gene Frequency, MESH : Female, Bowman Membrane, MESH: Genetic Association Studies, Aged, 80 and over, Corneal Dystrophies, Hereditary, Extracellular Matrix Proteins, MESH: Middle Aged, MESH : Amino Acid Sequence, MESH : Infant, Middle Aged, MESH : Adult, MESH: Infant, Pedigree, MESH : Phenotype, Phenotype, Female, France, MESH : Mutation, MESH: Algeria, MESH: Models, Molecular, Research Article, Adult, MESH: Mutation, Genotype, MESH: Pedigree, MESH : Models, Molecular, MESH : Bowman Membrane, MESH : Male, Molecular Sequence Data, MESH: Genetic Linkage, MESH: Corneal Dystrophies, Hereditary, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Phenotype, MESH : Extracellular Matrix Proteins, [SDV.CAN] Life Sciences [q-bio]/Cancer, Algeria/ethnology, Alleles, Amino Acid Sequence, Bowman Membrane/metabolism, Bowman Membrane/pathology, Corneal Dystrophies, Hereditary/classification, Corneal Dystrophies, Hereditary/epidemiology, Corneal Dystrophies, Hereditary/ethnology, Corneal Dystrophies, Hereditary/genetics, Corneal Dystrophies, Hereditary/pathology, Extracellular Matrix Proteins/genetics, Extracellular Matrix Proteins/metabolism, France/epidemiology, Genetic Association Studies, Humans, Infant, Mutation, Transforming Growth Factor beta/genetics, Transforming Growth Factor beta/metabolism, MESH: Gene Frequency, MESH : Middle Aged, MESH : Aged, 80 and over, MESH : France, MESH: Transforming Growth Factor beta, MESH: Humans, MESH: Molecular Sequence Data, MESH: Alleles, MESH : Humans, MESH: Adult, MESH : Genetic Association Studies, MESH : Genetic Linkage, MESH: Male, eye diseases, MESH: France, MESH : Transforming Growth Factor beta, Algeria, MESH : Pedigree, MESH : Corneal Dystrophies, Hereditary, MESH : Alleles, MESH: Female, MESH: Bowman Membrane
Abstract: International audience; PURPOSE: Investigate the genotype-phenotype correlations for five TGFBI (transforming growth factor, beta-induced) mutations including one novel pathogenic variant and one complex allele affecting the fourth FAS1 domain of keratoepithelin, and their potential effects on the protein's structure. METHODS: Three unrelated families were clinically diagnosed with lattice corneal dystrophy (CD) and one with an unclassified CD of Bowman's layer. Mutations in the TGFBI gene were detected by direct sequencing, and the functional impact of each variant was predicted using in silico algorithms. Corneal phenotypes, including histological examinations, were compared with the literature data. Furthermore, molecular modeling studies of these mutations were performed. RESULTS: Two distinct missense mutations affecting the same residue at position 509 of keratoepithelin: p.Leu509Pro (c.1526T>C) and p.Leu509Arg (c.1526T>G) were found to be associated with a lattice-type CD. The novel p.Val613Gly (c.1828T>G) TGFBI mutation was found in a sporadic case of an Algerian individual affected by lattice CD. Finally, the Bowman's layer CD was linked to the association in cis of the p.Met502Val and p.Arg555Gln variants, leading to the reclassification of this CD as atypical Thiel-Behnke CD. Structural modeling of these TGFBI mutations argues in favor of these mutations being responsible for instability and/or incorrect folding of keratoepithelin, predictions that are compatible with the clinical diagnoses. CONCLUSIONS: Description of a novel TGFBI mutation and a complex TGFBI allele further extends the mutational spectrum of TGFBI. Moreover, we show convincing evidence that TGFBI mutations affecting Leu509 are linked to the lattice phenotype in two unrelated French families, contrasting with findings previously reported. The p.Leu509Pro was reported to be associated with both amyloid and non-amyloid aggregates, whereas p.Leu509Arg has been described as being responsible for Epithelial Basement Membrane Dystrophy (EBMD).
Published: 2011

22. Mutational analysis of the PLCE1 gene in steroid resistant nephrotic syndrome

Author: Ilmay Bilge, Corinne Antignac, Zelal Z. Bircan, Marie-Claire Gubler, Marie-Alice Macher, Olivier Gribouval, Olivia Boyer, Lisa M. Guay-Woodford, Fabien Nevo, Geneviève Benoit, Robert R. Weiss, Chantal Loirat, Kenza Soulami, Constantinos J. Stefanidis, Audrey Pawtowski, Georges Deschênes, Michelle Hall, Neuropathies héréditaires et rein en développement, Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Génétique Médicale [CHU Necker], CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), Department of Pediatrics, Istanbul Faculty of Medicine, Department of Pediatric Nephrology, Kocaeli University Hospital, AP-HP, Service de Néphrologie Pédiatrique, Hôpital Robert Debré, Paris, Department of Genetics, UAB Center for Clinical and Translational Science, Birmingham, Department of Pediatric Nephrology, Hôpital Universitaire des Enfants - Reine Fabiola, Brussels, Service de Néphrologie Dialyse Transplantation, CHU Ibn Rochd, Casablanca, Department of Pediatric Nephrology, Department of Pediatric Nephrology, Maria Fareri Children's Hospital, Valhalla, New York, Néphropathies héréditaires et rein en développement (UMR_S 983), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de néphrologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de néphrologie pédiatrique, Université de Montréal (UdeM)-CHU Sainte Justine [Montréal], Department of Pediatrics, Istanbul University, Kocaeli University Hospital, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Department of Genetics, UAB Center for Clinical and Translational Science, Université libre de Bruxelles (ULB)-Hôpital Universitaire des Enfants Reine Fabiola [Bruxelles, Belgique] (HUDERF), Service de Néphrologie Dialyse Transplantation, CHU Ibn Rochd [Casablanca], 'P. & A. Kyriakou' Children's Hospital, Maria Fareri Children's Hospital, Financial support for this work was provided by grants from the Programme Hospitalier de Recherche Clinique (PHRC) AOM02123 (to C.A), the Association pour l'utilisation du Rein Artificiel (AURA) (to C.A), PodoNet (Clinical, Genetic and Experimental Research into Hereditary Diseases of the Podocyte) - project of the 2007 E-RARE program (to CA) and Fonds de la Recherche en Santé Québec (FRSQ) (Fellowship training Award to G.B.)., CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM), New York Medical College (NYMC), Gribouval, Olivier, Néphropathies héréditaires et rein en développement ( UMR_S 983 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -CHU Necker - Enfants Malades [AP-HP], Université de Montréal-CHU Sainte Justine [Montréal], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ), and Université Libre de Bruxelles [Bruxelles] ( ULB ) -Hôpital Universitaire des Enfants - Reine Fabiola
Subjects: Male, Candidate gene, Nephrotic Syndrome, DNA Mutational Analysis, MESH : Aged, 030232 urology & nephrology, [SDV.GEN] Life Sciences [q-bio]/Genetics, MESH : Child, Preschool, medicine.disease_cause, Compound heterozygosity, Cohort Studies, 0302 clinical medicine, Focal segmental glomerulosclerosis, MESH: Aged, 80 and over, Phosphoinositide Phospholipase C, MESH : Child, PLCE1, MESH: Child, Missense mutation, MESH : Female, Molecular genetics, MESH: DNA Mutational Analysis, Child, MESH: Cohort Studies, Genetics (clinical), Genetics, MESH: Aged, Aged, 80 and over, 0303 health sciences, Mutation, MESH: Statistics, Nonparametric, MESH : Phosphoinositide Phospholipase C, MESH: Middle Aged, Renal Medicine, Glomerulosclerosis, Focal Segmental, MESH: Genetic Predisposition to Disease, MESH : Infant, MESH : Adult, Middle Aged, MESH: Infant, 3. Good health, MESH : Phenotype, Phenotype, Child, Preschool, Screening, Female, Steroids, MESH : Mutation, Adult, medicine.medical_specialty, MESH: Mutation, Adolescent, MESH: Glomerulosclerosis, Focal Segmental, MESH : Male, MESH : Nephrotic Syndrome, MESH : Cohort Studies, MESH : DNA Mutational Analysis, Biology, MESH: Phenotype, Statistics, Nonparametric, 03 medical and health sciences, MESH : Adolescent, medicine, MESH: Phosphoinositide Phospholipase C, Humans, MESH : Middle Aged, Genetic Predisposition to Disease, MESH : Aged, 80 and over, MESH : Statistics, Nonparametric, 030304 developmental biology, Aged, MESH: Adolescent, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, MESH : Humans, MESH: Child, Preschool, Infant, MESH: Adult, medicine.disease, mutations, MESH: Male, MESH: Steroids, Steroid-resistant nephrotic syndrome, MESH : Glomerulosclerosis, Focal Segmental, MESH : Genetic Predisposition to Disease, MESH: Nephrotic Syndrome, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, MESH: Female, MESH : Steroids
Abstract: International audience; BACKGROUND: Mutations in the PLCE1 gene encoding phospholipase C epsilon 1 (PLCepsilon1) have been recently described in patients with early onset nephrotic syndrome (NS) and diffuse mesangial sclerosis (DMS). In addition, two cases of PLCE1 mutations associated with focal segmental glomerulosclerosis (FSGS) and later NS onset have been reported. METHOD: In order to better assess the spectrum of phenotypes associated with PLCE1 mutations, mutational analysis was performed in a worldwide cohort of 139 patients (95 familial cases belonging to 68 families and 44 sporadic cases) with steroid resistant NS presenting at a median age of 23.0 months (range 0-373). RESULTS: Homozygous or compound heterozygous mutations were identified in 33% (8/24) of DMS cases. PLCE1 mutations were found in 8% (6/78) of FSGS cases without NPHS2 mutations. Nine were novel mutations. No clear genotype-phenotype correlation was observed, with either truncating or missense mutations detected in both DMS and FSGS, and leading to a similar renal evolution. Surprisingly, three unaffected and unrelated individuals were also found to carry the homozygous mutations identified in their respective families. CONCLUSION: PLCE1 is a major gene of DMS and is mutated in a non-negligible proportion of FSGS cases without NPHS2 mutations. Although additional variants in 19 candidate genes (16 other PLC genes, BRAF,IQGAP1 and NPHS1) were not identified, it is speculated that other modifier genes or environmental factors may play a role in the renal phenotype variability observed in individuals bearing PLCE1 mutations. This observation needs to be considered in the genetic counselling offered to patients.
Published: 2010
Full Text: View/download PDF

23. Well-differentiated and dedifferentiated liposarcomas

Author: Jean-Michel Coindre, Alain Aurias, Florence Pedeutour, Plateforme de génétique moléculaire des cancers d'Aquitaine, Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Institut de signalisation, biologie du développement et cancer (ISBDC), Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA), Unité de génétique et biologie des cancers (U830), Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5), Institut Bergonié - CRLCC Bordeaux, Institut de signalisation, biologie du développement et cancer ( ISBDC ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Unité de génétique et biologie des cancers ( U830 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut Curie-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), and Université Paris Descartes - Paris 5 (UPD5)-Institut Curie-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Pathology, MESH: Hydrogen-Ion Concentration, MESH: Phosphotransferases, Atypical Lipomatous Tumor, 0302 clinical medicine, MESH: Hexokinase, MESH : Gene Frequency, MESH : Temperature, [SDV.BDD]Life Sciences [q-bio]/Development Biology, 0303 health sciences, Molecular pathology, Soft tissue sarcoma, MESH: Erythrocytes, Anatomical pathology, Proto-Oncogene Proteins c-mdm2, General Medicine, Liposarcoma, MESH: European Continental Ancestry Group, Prognosis, MESH: Temperature, MESH: Genes, 3. Good health, MESH : Phenotype, 030220 oncology & carcinogenesis, MESH : Genes, MESH : Phosphotransferases, medicine.medical_specialty, MESH : United States, MESH: Pedigree, Biology, MESH: Phenotype, MESH : African Continental Ancestry Group, Pathology and Forensic Medicine, MESH : European Continental Ancestry Group, 03 medical and health sciences, MESH : Hydrogen-Ion Concentration, medicine, MESH: United States, MESH: Gene Frequency, Humans, [ SDV.BDD ] Life Sciences [q-bio]/Development Biology, Molecular Biology, neoplasms, 030304 developmental biology, MESH: Humans, MESH: Alleles, MESH : Humans, Gene Amplification, Cancer, Cyclin-Dependent Kinase 4, Cell Biology, MESH : Hexokinase, medicine.disease, body regions, MESH : Pedigree, Karyotyping, Genomic Profile, Cancer research, Histopathology, MESH: African Continental Ancestry Group, MESH : Alleles, MESH : Erythrocytes
Abstract: International audience; Atypical lipomatous tumor or well-differentiated liposarcoma (ALT-WDLPS) and dedifferentiated liposarcoma (DDLPS) share the same basic genetic abnormality characterized by a simple genomic profile with a 12q14-15 amplification involving MDM2 gene. These tumors are the most frequent LPS. This paper reviews the molecular pathology, general clinical and imaging features, histopathology, new diagnostic tools, and prognosis of ALT-WDLPS and DDLPS.
Published: 2010
Full Text: View/download PDF

24. Characterization of a new β(1-3)glucan branching activity of Aspergillus fumigatus

Author: Isabelle Mouyna, Jean-Paul Latgé, Cécile Clavaud, Amandine Gastebois, Thierry Fontaine, Muriel Delepierre, Catherine Simenel, Bernadette Coddeville, Aspergillus, Institut Pasteur [Paris], Résonance Magnétique Nucléaire des Biomolécules, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Institut National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 ( UGSF ), and Institut National de la Recherche Agronomique ( INRA ) -Université de Lille-Centre National de la Recherche Scientifique ( CNRS )
Subjects: Glycosylation, beta-Glucans, MESH : beta-Glucans, MESH: Cellulases, Mutant, Glycobiology and Extracellular Matrices, MESH : Blotting, Western, MESH : Gas Chromatography-Mass Spectrometry, Biochemistry, Beta-glucan, Aspergillus fumigatus, chemistry.chemical_compound, Cell Wall, MESH: Nuclear Magnetic Resonance, Biomolecular, MESH : Fungal Proteins, Cellulases, Laminaribiose, [ SDV.MP.MYC ] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Chromatography, High Pressure Liquid, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, chemistry.chemical_classification, 0303 health sciences, biology, MESH: beta-Glucans, Glucan Endo-1,3-beta-D-Glucosidase, MESH : Glycosylation, Oligosaccharide, MESH: Glycosylation, MESH: Glucan Endo-1,3-beta-D-Glucosidase, MESH : Phenotype, Phenotype, Electrophoresis, Polyacrylamide Gel, MESH: Fungal Proteins, MESH : Mutation, MESH: Aspergillus fumigatus, MESH: Mutation, Blotting, Western, MESH : Nuclear Magnetic Resonance, Biomolecular, MESH : Electrophoresis, Polyacrylamide Gel, MESH: Phenotype, Gas Chromatography-Mass Spectrometry, Fungal Proteins, Cell wall, MESH : Chromatography, High Pressure Liquid, 03 medical and health sciences, MESH: Cell Wall, MESH: Blotting, Western, MESH: Chromatography, High Pressure Liquid, Nuclear Magnetic Resonance, Biomolecular, Molecular Biology, MESH : Cell Wall, 030304 developmental biology, Aspergillus, [ SDV ] Life Sciences [q-bio], 030306 microbiology, MESH : Glucan Endo-1,3-beta-D-Glucosidase, Cell Biology, biology.organism_classification, MESH: Gas Chromatography-Mass Spectrometry, Enzyme, chemistry, MESH : Aspergillus fumigatus, Mutation, MESH : Cellulases, [ SDV.BBM.BS ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], MESH: Electrophoresis, Polyacrylamide Gel
Abstract: International audience; A new HPLC method was developed to separate linear from beta(1-6)-branched beta(1-3)-glucooligosaccharides. This methodology has permitted the isolation of the first fungal beta(1-6)/beta(1-3)-glucan branching transglycosidase using a cell wall autolysate of Aspergillus fumigatus (Af). The encoding gene, AfBGT2 is an ortholog of AfBGT1, another transglycosidase of A. fumigatus previously analyzed (Mouyna, I., Hartland, R. P., Fontaine, T., Diaquin, M., Simenel, C., Delepierre, M., Henrissat, B., and Latgé, J. P. (1998) Microbiology 144, 3171-3180). Both enzymes release laminaribiose from the reducing end of a beta(1-3)-linked oligosaccharide and transfer the remaining chain to another molecule of the original substrate. The AfBgt1p transfer occurs at C-6 of the non-reducing end group of the acceptor, creating a kinked beta(1-3;1-6) linear molecule. The AfBgt2p transfer takes place at the C-6 of an internal group of the acceptor, resulting in a beta(1-3)-linked product with a beta(1-6)-linked side branch. The single Afbgt2 mutant and the double Afbgt1/Afbgt2 mutant in A. fumigatus did not display any cell wall phenotype showing that these activities were not responsible for the construction of the branched beta(1-3)-glucans of the cell wall.
Published: 2010
Full Text: View/download PDF

25. Sumoylation by Ubc9 Regulates the Stem Cell Compartment and Structure and Function of the Intestinal Epithelium in Mice

Author: Esther Danenberg, Alexandra Andrieux, Karim Nacerddine, Ana Cumano, Ghislaine Hamard, Perrine Bomme, Grégory Jouvion, Anne Dejean, Béatrice Romagnolo, Maud D. Demarque, Nick Barker, Hélène Neyret–Kahn, Hans Clevers, Benoit Terris, Hubrecht Institute for Developmental Biology and Stem Cell Research, Organisation Nucléaire et Oncogenèse / Nuclear Organization and Oncogenesis, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Histotechnologie et Pathologie, Institut Pasteur [Paris], Microscopie Ultrastructurale (Plate-forme), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Plateforme Recombinaison Homologue, Transfert d'Embryons et Cryoconservation [Institut Cochin] (PRHTEC), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin (UMR_S567 / UMR 8104), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Service d'Anatomie Pathologique, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Développement des Lymphocytes, Organisation Nucléaire et Oncogenèse, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Plateforme Recombinaison Homologue, Transfert d'Embryons et Cryoconservation [Institut Cochin] ( PRHTEC ), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), CHU Cochin [AP-HP], Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: SUMO protein, MESH : Tamoxifen, MESH: Mice, Knockout, Mice, 0302 clinical medicine, Keratin, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Animals, Intestinal Mucosa, health care economics and organizations, chemistry.chemical_classification, Mice, Knockout, 0303 health sciences, Stem Cells, MESH: Sumoylation, Gastroenterology, LGR5, MESH : Sumoylation, Intestinal epithelium, Cell biology, MESH : Phenotype, medicine.anatomical_structure, Phenotype, Biochemistry, MESH : Stem Cells, MESH: Intestinal Mucosa, [SDV.IMM]Life Sciences [q-bio]/Immunology, Basal lamina, Stem cell, MESH : Ubiquitin-Conjugating Enzymes, education, MESH: Stem Cells, Biology, MESH: Phenotype, MESH : Intestinal Mucosa, 03 medical and health sciences, MESH : Mice, medicine, Animals, MESH: Mice, 030304 developmental biology, Hepatology, Sumoylation, Small intestine, MESH: Ubiquitin-Conjugating Enzymes, Tamoxifen, chemistry, Ubiquitin-Conjugating Enzymes, Keratin 8, MESH : Mice, Knockout, MESH: Tamoxifen, MESH : Animals, 030217 neurology & neurosurgery
Abstract: Background & Aims Small ubiquitin-like modifiers (SUMOs) are attached to other proteins to regulate their function (sumoylation). We investigated the role of Ubc9, which covalently attaches SUMOs to proteins, in the gastrointestinal tract of adult mice. Methods We investigated the effects of decreased sumoylation in adult mammals by generating mice with an inducible knockout (by injection of 4-hydroxytamoxifen) of the E2 enzyme Ubc9 ( Ubc9fl/-/ROSA26-CreERT2 mice). We analyzed the phenotypes using a range of histologic techniques. Results Loss of Ubc9 from adult mice primarily affected the small intestine. Ubc9fl/−/ROSA26-CreERT2 mice died within 6 days of 4-hydroxytamoxifen injection, losing 20% or less of their body weight and developing severe diarrhea on the second day after injection. Surprisingly, other epithelial tissues appeared to be unaffected at that stage. Decreased sumoylation led to the depletion of the intestinal proliferative compartment and to the rapid disappearance of stem cells. Sumoylation was required to separate the proliferative and differentiated compartments from the crypt and control differentiation and function of the secretory lineage. Sumoylation was required for nucleus positioning and polarized organization of actin in the enterocytes. Loss of sumoylation caused detachment of the enterocytes from the basal lamina, as observed in tissue fragility diseases. We identified the intermediate filament keratin 8 as a SUMO substrate in epithelial cells. Conclusions Sumoylation maintains intestinal stem cells and the architecture, mechanical stability, and function of the intestinal epithelium of mice.
Published: 2010
Full Text: View/download PDF

26. Comparison of clinical presentations and outcomes between patients with TGFBR2 and FBN1 mutations in Marfan syndrome and related disorders

Author: David Attias, Philippe Gabriel Steg, Franck Iserin, Daniel Sidi, Mireille Claustres, Laurence Faivre, Marlène Rio, Marie-Ange Delrue, Philippe Ravaud, Catherine Boileau, Carine Roy, Christine Francannet, Henri Plauchu, Sylvie Odent, Christophe Béroud, Guillaume Jondeau, Martine Le Merrer, Chantal Stheneur, Gwenaëlle Collod-Béroud, Stanislas Lyonnet, Philippe Khau Van Kien, Annick Rossi, Laurence Cohen, Didier Lacombe, Delphine Detaint, Consultation Marfan, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bichat, Service de cardiologie, Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pédiatrie, urgences enfants [CHU Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Ambroise Paré [AP-HP], Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département d'épidémiologie, biostatistique et recherche clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], 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 de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de génétique médicale, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Unité de Cardiologie Pédiatrique, Hôpital Privé Jacques Cartier [Massy], Unité de Génétique Médicale, Hôtel-Dieu-CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I (UdA), Service de cardiologie pédiatrique [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Service de Génétique Médicale [CHU Necker], Service de Génétique Clinique, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Sud, Service de Génétique, Hôpital de l'Hôtel Dieu [CHU-HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Service de génétique [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biochimie, d'hormonologie et de génétique moléculaire [CHU Amrboise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 (UPD7), Service de pédiatrie, urgences enfants [Ambroise-Paré], Hôpital Ambroise Paré [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Galilée, Service de biochimie, d'hormonologie et de génétique moléculaire [Amrboise Paré], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Ambroise Paré [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bichat, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Laboratoire de Recherche Magellan, Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Institut d'Administration des Entreprises (IAE) - Lyon, Service de Génétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], CHU Necker - Enfants Malades [AP-HP], Unité de génétique médicale, hôpital Sud, Hôpital Bichat - Claude Bernard, Modèles et méthodes de l'évaluation thérapeutique des maladies chroniques (U738 / UMR_S738), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bichat, Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de pédiatrie, urgences enfants, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, Université Paris Diderot - Paris 7 ( UPD7 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques, Université Montpellier 1 ( UM1 ) -IFR3-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Université de Bordeaux ( UB ) -CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Hôtel-Dieu-CHU Clermont-Ferrand-Université d'Auvergne - Clermont-Ferrand I ( UdA ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -Hôpital Sud, Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Hôtel Dieu, CHU Rouen-Université de Rouen Normandie ( UNIROUEN ), Normandie Université ( NU ) -Normandie Université ( NU ), Hémostase, bio-ingénierie et remodelage cardiovasculaires ( LBPC ), Université Paris 13 ( UP13 ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Galilée, Service de biochimie, d'hormonologie et de génétique moléculaire, IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Recherche Magellan, Institut d'Administration des Entreprises (IAE) - Lyon-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Diderot - Paris 7 (UPD7), and COLLOD-BEROUD, Gwenaëlle
Subjects: Male, MESH : Receptors, Transforming Growth Factor beta, MESH : Mitral Valve Prolapse, Gene mutation, Gastroenterology, Marfan Syndrome, 0302 clinical medicine, MESH: Pregnancy, MESH : Child, Pregnancy, Mitral valve, MESH: Child, Medicine, MESH: Incidence, Child, MESH: Aneurysm, Dissecting, Aortic dissection, 0303 health sciences, Mitral Valve Prolapse, MESH: Middle Aged, Incidence, Prognosis, MESH: Case-Control Studies, MESH : Incidence, Aortic Aneurysm, 3. Good health, Survival Rate, MESH : Phenotype, MESH: Young Adult, Cardiology and Cardiovascular Medicine, musculoskeletal diseases, MESH : Case-Control Studies, medicine.medical_specialty, MESH : Young Adult, MESH : Cohort Studies, Fibrillins, MESH: Phenotype, Sudden death, MESH: Prognosis, MESH: Protein-Serine-Threonine Kinases, 03 medical and health sciences, MESH: Mitral Valve Prolapse, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH : Adolescent, Physiology (medical), Humans, MESH : Middle Aged, MESH : Aneurysm, Dissecting, MESH: Adolescent, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, MESH : Humans, Receptor, Transforming Growth Factor-beta Type II, Case-control study, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, MESH: Adult, medicine.disease, MESH: Aortic Aneurysm, MESH : Pregnancy, MESH : Mitral Valve Insufficiency, Case-Control Studies, Mutation, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, Receptors, Transforming Growth Factor beta, MESH: Female, Marfan syndrome, MESH: Mitral Valve Insufficiency, Fibrillin-1, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, [SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Cohort Studies, MESH : Female, MESH: Kaplan-Meiers Estimate, MESH: Cohort Studies, MESH : Prognosis, Incidence (epidemiology), Microfilament Proteins, Mitral Valve Insufficiency, MESH : Adult, [ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Middle Aged, MESH : Survival Rate, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, MESH : Aortic Aneurysm, Phenotype, medicine.anatomical_structure, Female, MESH: Receptors, Transforming Growth Factor beta, MESH : Mutation, MESH : Protein-Serine-Threonine Kinases, Adult, MESH: Mutation, MESH : Microfilament Proteins, Adolescent, MESH: Survival Rate, MESH : Male, [SDV.GEN.GH] Life Sciences [q-bio]/Genetics/Human genetics, Protein Serine-Threonine Kinases, MESH: Marfan Syndrome, Young Adult, MESH: Microfilament Proteins, Internal medicine, Survival rate, 030304 developmental biology, MESH : Marfan Syndrome, business.industry, MESH : Kaplan-Meiers Estimate, MESH: Male, Surgery, Aortic Dissection, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, business
Abstract: Background— TGFBR2 mutations were recognized recently among patients with a Marfan-like phenotype. The associated clinical and prognostic spectra remain unclear. Methods and Results— Clinical features and outcomes of 71 patients with a TGFBR2 mutation (TGFBR2 group) were compared with 50 age- and sex-matched unaffected family members (control subjects) and 243 patients harboring FBN1 mutations (FBN1 group). Aortic dilatation was present in a similar proportion of patients in both the TGFBR2 and FBN1 groups (78% versus 79%, respectively) but was highly variable. The incidence and average age for thoracic aortic surgery (31% versus 27% and 35±16 versus 39±13 years, respectively) and aortic dissection (14% versus 10% and 38±12 versus 39±9 years) were also similar in the 2 groups. Mitral valve involvement (myxomatous, prolapse, mitral regurgitation) was less frequent in the TGFBR2 than in the FBN1 group (all P TGFBR2 mutations, versus 32% with FBN1 mutations ( P =0.002). The rate of death was greater in TGFBR2 families before diagnosis but similar once the disease had been recognized. Most pregnancies were uneventful (without death or aortic dissection) in both TGFBR2 and FBN1 families (38 of 39 versus 213 of 217; P =1). Seven patients (10%) with a TGFBR2 mutation fulfilled international criteria for Marfan syndrome, 3 of whom presented with features specific for Loeys-Dietz syndrome. Conclusions— Clinical outcomes appear similar between treated patients with TGFBR2 mutations and individuals with FBN1 mutations. Prognosis depends on clinical disease expression and treatment rather than simply the presence of a TGFBR2 gene mutation.
Published: 2009
Full Text: View/download PDF

27. Genotype-phenotype correlation in four 15q24 deleted patients identified by array-CGH

Author: Bruno Delobel, Emilie Landais, Tania Attié-Bitach, Martine Doco-Fenzy, ElÃ©onore Blondeel, MarlÃ¨ne Rio, Joris Andrieux, Elsa Delaby, ChristÃ¨le Dubourg, Sylvie Manouvrier-Hanu, Muriel Holder-Espinasse, Henri Copin, Hubert Journel, Sylvie Odent, MichÃ¨le Mathieu, Laboratoire de Génétique Clinique, Hôpital Jeanne de Flandre [Lille]-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire de Génétique Moléculaire et Hormonologie, Hôpital Pontchaillou, Service de Génétique Médicale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pédiatrie-Génétique, CHU Amiens-Picardie-Hôpital nord, Génétique Médicale, Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA)-Hôpital Chubert, Laboratoire de Cytogénétique, Université de Picardie Jules Verne (UPJV)-CHU Amiens-Picardie, Service de Génétique, Centre Hospitalier Universitaire de Reims (CHU Reims)-Hôpital Maison Blanche-IFR 53, Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA), Centre de Génétique Chromosomique, Hôpital Saint Vincent de Paul-GHICL, Service de Génétique clinique, Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), De Villemeur, Hervé, Laboratoire de génétique moléculaire et génomique médicale [CHU Rennes], CHU Pontchaillou [Rennes], Hôpital Saint Vincent de Paul-Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Hôpital Jeanne de Flandre [Lille]-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Centre Hospitalier Bretagne Atlantique-Hôpital Chubert, Université de Picardie Jules Verne ( UPJV ) -CHU Amiens-Picardie, Centre Hospitalier Universitaire de Reims ( CHU Reims ) -Hôpital Maison Blanche-IFR 53, Université de Reims Champagne-Ardenne ( URCA ) -Université de Reims Champagne-Ardenne ( URCA ), and Hôpital Jeanne de Flandre [Lille]-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille )
Subjects: Male, Pathology, MESH : Genotype, [SDV.GEN] Life Sciences [q-bio]/Genetics, MESH : Child, Preschool, MESH: Genotype, 0302 clinical medicine, MESH: Pregnancy, MESH : Child, Pregnancy, MESH: Child, Genotype, MESH : Female, Child, MESH : Comparative Genomic Hybridization, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Genetics (clinical), Genetics, 0303 health sciences, Comparative Genomic Hybridization, MESH: Infant, Newborn, Long philtrum, MESH : Infant, Chromosome Breakage, Micropenis, MESH : Chromosomes, Human, Pair 15, MESH: Infant, 3. Good health, MESH : Phenotype, Phenotype, MESH: Chromosome Breakage, Child, Preschool, Female, Chromosome breakage, Chromosome Deletion, Haploinsufficiency, medicine.medical_specialty, congenital, hereditary, and neonatal diseases and abnormalities, MESH : Male, MESH: Chromosome Deletion, 15q24 deletion, Biology, genotype-phenotype correlation, MESH : Infant, Newborn, MESH: Phenotype, Article, 03 medical and health sciences, [SDV.BDD] Life Sciences [q-bio]/Development Biology, medicine, Humans, [ SDV.BDD ] Life Sciences [q-bio]/Development Biology, 030304 developmental biology, Chromosomes, Human, Pair 15, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, MESH : Humans, MESH: Child, Preschool, Infant, Newborn, Infant, medicine.disease, MESH : Chromosome Deletion, Iris coloboma, MESH: Male, MESH: Comparative Genomic Hybridization, MESH : Pregnancy, Palpebral fissure, MESH : Chromosome Breakage, Hypospadias, array-CGH, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, MESH: Female, 030217 neurology & neurosurgery, MESH: Chromosomes, Human, Pair 15
Abstract: International audience; Microdeletion 15q24 is an emerging syndrome recently described, mainly due to increased use of array-CGH. Clinical features associate mild to moderate developmental delay, typical facial characteristics (high forehead and frontal hairline, broad eyebrows, downslanting palpebral features, long philtrum), hands (particularly proximal implanted thumbs) and genital anomalies (micropenis, hypospadias). We report here on four de novo cases having 2.5-6.1 Mb deletions involving 15q24: one 15q23q24.2 (Patient 1) and three 15q24.1q24.2 deletions (Patients 2-4). We correlate phenotype to genotype according to molecular boundaries of these deletions. Since bilateral iris coloboma and severe ano-rectal malformation were only present in Patient 1, we could link these anomalies to haploinsufficiency of 15q23 genes. Neither hypospadias nor micropenis were present in Patient 3 bearing the smallest deletion, therefore we could define 500 kb 15q24.1 region linked to these anomalies.
Published: 2009
Full Text: View/download PDF

28. Molecular and phenotypic evaluation of Lichtheimia corymbifera (formerly Absidia corymbifera) complex isolates associated with human mucormycosis: rehabilitation of L. ramosa

Author: Dea Garcia-Hermoso, Françoise Dromer, Damien Hoinard, Eric Dannaoui, Jean-Charles Gantier, Frédéric Grenouillet, Mycologie moléculaire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)
Subjects: Male, MESH: Sequence Analysis, DNA, Antifungal Agents, Lichtheimia corymbifera, MESH : Aged, chemistry.chemical_compound, Peptide Elongation Factor 1, MESH: Aged, 80 and over, Absidia, RNA, Ribosomal, 28S, Genotype, MESH : Female, MESH: Absidia, DNA, Fungal, Mycological Typing Techniques, Clade, MESH : Mycological Typing Techniques, MESH : DNA, Ribosomal Spacer, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, [ SDV.MP.MYC ] Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Aged, 80 and over, MESH: Aged, MESH: Microbial Sensitivity Tests, 0303 health sciences, MESH: Middle Aged, Melezitose, Middle Aged, MESH : Adult, MESH: RNA, Ribosomal, 28S, MESH : Phenotype, Phenotype, MESH : Peptide Elongation Factor 1, Female, Adult, Microbiology (medical), Adolescent, Sequence analysis, MESH : Male, MESH : Antifungal Agents, Mycology, Microbial Sensitivity Tests, Biology, MESH: Phenotype, Microbiology, 03 medical and health sciences, Species Specificity, MESH: Mycological Typing Techniques, MESH : Adolescent, DNA, Ribosomal Spacer, Humans, Mucormycosis, MESH: Species Specificity, MESH : Species Specificity, MESH : Middle Aged, MESH : Mucormycosis, MESH: Peptide Elongation Factor 1, Internal transcribed spacer, MESH : Aged, 80 and over, MESH: DNA, Ribosomal Spacer, Ribosomal DNA, Aged, MESH: Mucormycosis, 030304 developmental biology, MESH: Adolescent, MESH: Humans, 030306 microbiology, MESH : Humans, MESH: Adult, Sequence Analysis, DNA, MESH: Antifungal Agents, biology.organism_classification, MESH: Male, MESH: DNA, Fungal, MESH : RNA, Ribosomal, 28S, chemistry, MESH : Microbial Sensitivity Tests, MESH : Absidia, MESH : DNA, Fungal, MESH: Female, MESH : Sequence Analysis, DNA
Abstract: Thirty-eight isolates (including 28 isolates from patients) morphologically identified as Lichtheimia corymbifera (formerly Absidia corymbifera ) were studied by sequence analysis (analysis of the internal transcribed spacer [ITS] region of the ribosomal DNA, the D1-D2 region of 28S, and a portion of the elongation factor 1α [EF-1α] gene). Phenotypic characteristics, including morphology, antifungal susceptibility, and carbohydrate assimilation, were also determined. Analysis of the three loci uncovered two well-delimited clades. The maximum sequence similarity values between isolates from both clades were 66, 95, and 93% for the ITS, 28S, and EF-1α loci, respectively, with differences in the lengths of the ITS sequences being detected (763 to 770 bp for isolates of clade 1 versus 841 to 865 bp for isolates of clade 2). Morphologically, the shapes and the sizes of the sporangiospores were significantly different among the isolates from both clades. On the basis of the molecular and morphological data, we considered isolates of clade 2 to belong to a different species named Lichtheimia ramosa because reference strains CBS 269.65 and CBS 270.65 (which initially belonged to Absidia ramosa ) clustered within this clade. As neotype A. corymbifera strain CBS 429.75 belongs to clade 1, the name L. corymbifera was conserved for clade 1 isolates. Of note, the amphotericin B MICs were significantly lower for L. ramosa than for L. corymbifera ( P < 0.005) but were always ≤0.5 μg/ml for both species. Among the isolates tested, the assimilation of melezitose was positive for 67% of the L. ramosa isolates and negative for all L. corymbifera isolates. In conclusion, this study reveals that two Lichtheimia species are commonly associated with mucormycosis in humans.
Published: 2009
Full Text: View/download PDF

29. CC2D2A mutations in Meckel and Joubert syndromes indicate a genotype-phenotype correlation

Author: Ali Saad, Raymonde Bouvier, S. Romano, Nadia Elkhartoufi, Sophie Audollent, Anne Lise Delezoide, Sophie Saunier, Tania Attié-Bitach, Sophie Patrier, Nathalie Boddaert, Candice Babarit, Rémi Salomon, Jelena Martinovic, Marie Pierre Cordier, Enza Maria Valente, Chantal Esculpavit, Emmanuelle Szenker, Estelle Escudier, Soumaya Mougou-Zerelli, Marie Claire Gubler, Marie Gonzales, Michel Vekemans, Férechté Encha-Razavi, Arnold Munnich, Jeanne Amiel, Joelle Roume, Sylvie Odent, Philippe Loget, Marion Gérard, B. Leheup, Suonavy Khung, Sophie Thomas, Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Cytogénétique, Génétique moléculaire et Biologie de la reproduction, Hôpital Farhat Hached, Service de Génétique Médicale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de pédiatrie générale [CHU Necker], Neuropathies héréditaires et rein en développement, Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Physiopathologie des maladies génétiques d'expression pédiatrique, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Médecine Infantile III et Génétique Clinique [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Cabinet d'Anatomie et Cytologie Pathologiques Richier, Service de génétique clinique [Rennes], Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud, Service de génétique médicale, CHI Poissy-Saint-Germain, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Service de Biologie du Développement, Service de Génétique, Hospices Civils de Lyon (HCL), Centre de pathologie Est, Service de radiologie pédiatrique [CHU Necker], Imagerie Cerebrale en Psychiatrie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Istituto CSS Mendel [Rome, Italy], Department of Medical and Surgical Pediatrics, University Hospital, Messina, French National Research Agency (ANR) : ANR-06-MRAR-034-02United States Department of Health & Human Services National Institutes of Health (NIH) - USA : NS039818-07Fondazione Telethon : GGP08145INSERM-Direction generale de la recherche scientifique et de la renovation technologique (DGRSRT) : CS/RN/2008 56, CS/RN/2008 87, Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de génétique et embryologie médicales [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Trousseau [APHP], Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Centre Hospitalier Régional Universitaire de Nancy ( CHRU Nancy ), Service de génétique clinique, Hôpital Sud, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 ), Hospices Civils de Lyon ( HCL ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Istituto CSS Mendel, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), De Villemeur, Hervé, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), and hôpital Sud
Subjects: Male, TMEM67, MESH : Genotype, [SDV.GEN] Life Sciences [q-bio]/Genetics, Ciliopathies, MESH : Syndrome, Cohort Studies, MESH : Proteins, MESH: Genotype, 0302 clinical medicine, MESH: Gene Expression Regulation, Developmental, Missense mutation, Developmental, MESH: Syndrome, MESH: Proteins, MESH: Cohort Studies, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Genetics (clinical), In Situ Hybridization, MESH: Genetic Association Studies, Genetics, 0303 health sciences, Polydactyly, Gene Expression Regulation, Developmental, MESH : In Situ Hybridization, Syndrome, 3. Good health, MESH : Phenotype, Phenotype, RPGRIP1L, MESH : RNA Splicing, MESH : Mutation, MESH: Mutation, Genotype, RNA Splicing, MESH : Male, MESH : Cohort Studies, Genes, Recessive, Biology, CC2D2A, MESH: Phenotype, MESH: Nervous System Diseases, Article, Joubert syndrome, 03 medical and health sciences, MESH: In Situ Hybridization, [SDV.BDD] Life Sciences [q-bio]/Development Biology, medicine, Alleles, Gene Expression Regulation, Genes, Recessive, Genetic Association Studies, Humans, Mutation, Nervous System Diseases, Proteins, [ SDV.BDD ] Life Sciences [q-bio]/Development Biology, MESH: Genes, Recessive, 030304 developmental biology, Meckel-Gruber Syndrome, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Humans, urogenital system, MESH: Alleles, MESH : Humans, MESH : Genes, Recessive, MESH : Nervous System Diseases, MESH : Genetic Association Studies, medicine.disease, MESH: Male, Cytoskeletal Proteins, MESH : Gene Expression Regulation, Developmental, MESH : Alleles, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, MESH: RNA Splicing, 030217 neurology & neurosurgery
Abstract: International audience; Meckel-Gruber syndrome (MKS) is a lethal fetal disorder characterized by diffuse renal cystic dysplasia, polydactyly, a brain malformation that is usually occipital encephalocele, and/or vermian agenesis, with intrahepatic biliary duct proliferation. Joubert syndrome (JBS) is a viable neurological disorder with a characteristic "molar tooth sign" (MTS) on axial images reflecting cerebellar vermian hypoplasia/dysplasia. Both conditions are classified as ciliopathies with an autosomal recessive mode of inheritance. Allelism of MKS and JBS has been reported for TMEM67/MKS3, CEP290/MKS4, and RPGRIP1L/MKS5. Recently, one homozygous splice mutation with a founder effect was reported in the CC2D2A gene in Finnish fetuses with MKS, defining the 6th locus for MKS. Shortly thereafter, CC2D2A mutations were also reported in JBS. The analysis of the CC2D2A gene in our series of MKS fetuses, identified 14 novel truncating mutations in 11 cases. These results confirm the involvement of CC2D2A in MKS and reveal a major contribution of CC2D2A to the disease. We also identified three missense CC2D2A mutations in two JBS cases. Therefore, and in accordance with the data reported regarding RPGRIP1L, our results indicate phenotype-genotype correlations, as missense and presumably hypomorphic mutations lead to JBS while all null alleles lead to MKS.
Published: 2009
Full Text: View/download PDF

30. Usefulness of antimicrobial resistance pattern for detecting PVL- or TSST-1-producing meticillin-resistant Staphylococcus aureus in a French university hospital

Author: Daniel Talon, Xavier Bertrand, Houssein Gbaguidi-Haore, Michelle Thouverez, Gérard Couetdic, Pascal Cholley, Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), and Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)
Subjects: MESH : Leukocidins, Male, MESH : Retrospective Studies, MESH : Aged, MESH: Leukocidins, Hospitals, University, 0302 clinical medicine, MESH : Child, MESH: Superantigens, MESH: Child, MESH : Superantigens, Child, Aged, 80 and over, 0303 health sciences, Cross Infection, MESH: Middle Aged, Superantigens, MESH : Genes, Bacterial, MESH : Infant, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, General Medicine, Staphylococcal Infections, Antimicrobial, MESH: Infant, 3. Good health, Electrophoresis, Gel, Pulsed-Field, MESH : Phenotype, MESH: Electrophoresis, Gel, Pulsed-Field, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Staphylococcus aureus, MESH: Young Adult, Child, Preschool, MESH : Cross Infection, Microbiology (medical), Methicillin-Resistant Staphylococcus aureus, Fusidic acid, MESH : Molecular Epidemiology, MESH: Staphylococcal Infections, MESH : Young Adult, Exotoxins, MESH: Methicillin-Resistant Staphylococcus aureus, Microbial Sensitivity Tests, MESH: Phenotype, Microbiology, 03 medical and health sciences, Antibiotic resistance, MESH : Adolescent, MESH: Molecular Epidemiology, MESH : Methicillin-Resistant Staphylococcus aureus, Humans, MESH : Middle Aged, MESH : Aged, 80 and over, MESH : Hospitals, University, MESH : Electrophoresis, Gel, Pulsed-Field, Aged, Retrospective Studies, MESH: Adolescent, MESH: Humans, MESH: Methicillin Resistance, 030306 microbiology, MESH: Child, Preschool, MESH : Humans, Infant, MESH: Adult, MESH: Retrospective Studies, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses, Virology, MESH : Methicillin Resistance, MESH : Exotoxins, MESH : Staphylococcal Infections, MESH: Female, Meticillin, Drug resistance, MESH : Child, Preschool, medicine.disease_cause, Enterotoxins, MESH: Aged, 80 and over, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, Leukocidins, MESH: Enterotoxins, MESH : Female, 030212 general & internal medicine, MESH : Enterotoxins, MESH: Aged, MESH: Microbial Sensitivity Tests, Molecular Epidemiology, MESH: Infant, Newborn, MESH : Adult, Middle Aged, Phenotype, Female, France, MESH: Genes, Bacterial, medicine.drug, Adult, Adolescent, MESH : Male, Bacterial Toxins, MESH : Infant, Newborn, Young Adult, medicine, MESH : France, MESH: Hospitals, University, business.industry, Infant, Newborn, MESH: Cross Infection, MESH: Exotoxins, MESH: Male, Multiple drug resistance, MESH: France, MESH: Bacterial Toxins, Genes, Bacterial, MESH : Bacterial Toxins, Multilocus sequence typing, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Methicillin Resistance, MESH : Microbial Sensitivity Tests, business
Abstract: Several recent reports have suggested that community-associated meticillin-resistant Staphylococcus aureus (MRSA) clones, particularly those harbouring genes for Panton–Valentine leukocidin (PVL) or toxic shock syndrome toxin 1 (TSST-1), are increasingly responsible for infections in hospitals. Here, a retrospective study was carried out to investigate whether antimicrobial resistance patterns could be used to detect these pathogens in a French university hospital. Isolates were characterized by antimicrobial susceptibility testing, PCR profiling (PVL genes and tst), PFGE typing and multilocus sequence typing. Demographic and clinical data were collected from all patients. For PVL-positive MRSA, the typical antimicrobial resistance pattern (susceptible to fluoroquinolones, non-susceptible to fusidic acid, kanamycin resistant and susceptible to gentamicin and tobramycin) had a sensitivity of 77.8 % and a positive predictive value (PPV) of 100 %. For tst-positive MRSA, the antimicrobial resistance pattern (susceptible to fluoroquinolones and non-susceptible to fusidic acid) had a sensitivity of 100 % and a PPV of 72.4 %. These results suggest that phenotypic rules based on antimicrobial resistance patterns are potentially useful for the detection of PVL- and tst-positive MRSA isolates.
Published: 2009
Full Text: View/download PDF

31. Plasmacytoid dendritic cells accumulate in spleens from chronically HIV-infected patients but barely participate in interferon-alpha expression

Author: Anne Hosmalin, Louis Kreitmann, Eric Oksenhendler, Leïla Perié, Bettina Fabiani, Jean Paul Viard, Jürgen Schmitz, Stéphanie Louis, Jean Pierre Marie, Laurent Chorro, Orly Abehsira-Amar, Thierry Jo Molina, Rémi Cheynier, Anne Berger, Seckou Diocou, Laurent Garderet, Michelina Nascimbeni, Stéphanie Beq, Jérôme Pacanowski, Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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), Miltenyi, hotel-dieu, service d'hématologie, Hôpital Hôtel Dieu, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'immunologie clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Département de Virologie - Department of Virology, Institut Pasteur [Paris] (IP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5), Service d'anatomie et cytologie pathologiques [CHU Saint-Antoine], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Saint-Antoine [APHP], Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Institut Pasteur [Paris], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris], Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Service d'anatomie et cytologie pathologiques, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Saint-Antoine [APHP], Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Assistance publique - Hôpitaux de Paris (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Diderot - Paris 7 ( UPD7 ) -Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], and Département de Virologie
Subjects: CD4-Positive T-Lymphocytes, Myeloid, MESH: Spleen, Fluorescent Antibody Technique, HIV Infections, MESH: Flow Cytometry, Plasmacytoid dendritic cell, Biochemistry, MESH: Antiretroviral Therapy, Highly Active, MESH: HIV-1, 0302 clinical medicine, MESH : Chronic Disease, Antiretroviral Therapy, Highly Active, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Fluorescent Antibody Technique, 0303 health sciences, MESH: Dendritic Cells, MESH: CD4-Positive T-Lymphocytes, hemic and immune systems, Hematology, MESH: HIV Infections, Flow Cytometry, Marginal zone, Endocytosis, 3. Good health, MESH : Phenotype, Phenotype, medicine.anatomical_structure, MESH : CD4-Positive T-Lymphocytes, MESH: Endocytosis, Red pulp, MESH : Interferon-alpha, [SDV.IMM]Life Sciences [q-bio]/Immunology, Inflammation Mediators, MESH: Interferon-alpha, MESH : HIV-1, MESH : Spleen, MESH : Flow Cytometry, MESH : Endocytosis, Immunology, MESH: Inflammation Mediators, Alpha interferon, Spleen, Biology, MESH: Phenotype, MESH : Inflammation Mediators, 03 medical and health sciences, MESH : HIV Infections, medicine, Humans, Antigen-presenting cell, 030304 developmental biology, MESH: Humans, MESH: Chronic Disease, MESH : Humans, Interferon-alpha, Dendritic Cells, Cell Biology, Dendritic cell, MESH : Antiretroviral Therapy, Highly Active, Virology, MESH : Fluorescent Antibody Technique, MESH : Dendritic Cells, Chronic Disease, HIV-1, 030215 immunology
Abstract: We characterized the localization, phenotype, and some functions of plasmacytoid dendritic cells (pDCs) in the human spleen. pDCs were localized in the marginal zone and the periarteriolar region. Some were also found in the red pulp. pDCs were immature by phenotypic labeling, consistently with their capacity to internalize Dextran in a functional assay. In spleens from HIV-infected patients with thrombocytopenic purpura, these characteristics were unaffected. However, an accumulation of pDCs, but not myeloid dendritic cells (mDCs), was observed in some HIV+ patients, correlating with high proviral loads. Moreover, although undetectable in most HIV− patients, interferon-α (IFN-α) production was evidenced in situ and by flow cytometry in most HIV+ patients. IFN-α was located in the marginal zone. Surprisingly, IFN-α colocalized only with few pDCs, but rather with other cells, including T and B lymphocytes, mDCs, and macrophages. Therefore, pDCs accumulated in spleens from HIV+ patients with high proviral loads, but they did not seem to be the main IFN-α producers.
Published: 2009
Full Text: View/download PDF

32. Phenotypic spectrum of STRA6 mutations: from Matthew-Wood syndrome to non-lethal anophthalmia

Author: Nicolas, Chassaing, Christelle, Golzio, Sylvie, Odent, Léopoldine, Lequeux, Adeline, Vigouroux, Jelena, Martinovic-Bouriel, Francesco Danilo, Tiziano, Lucia, Masini, Francesca, Piro, Giovanna, Maragliano, Anne-Lise, Delezoide, Tania, Attié-Bitach, Sylvie, Manouvrier-Hanu, Heather C, Etchevers, Patrick, Calvas, Service de génétique médicale, CHU Toulouse [Toulouse]-Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), IFR Necker-Enfants Malades (IRNEM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique clinique, hôpital Sud, Institut de Génétique et Développement de Rennes (IGDR), Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Génétique Médicale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Institute of Medical Genetics, Università cattolica del Sacro Cuore [Milano] (Unicatt), Institute of Obstetrics and Gynecology, Operative Unit of Pathology, San Giovanni Ospedale, Complex Unit of Neonatology, Service de Biologie du Développement, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Laboratoire de Génétique Clinique, Hôpital Jeanne de Flandre [Lille]-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), De Villemeur, Hervé, Service Génétique Médicale [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de génétique clinique [Rennes], Université de Rennes (UR)-CHU Pontchaillou [Rennes]-hôpital Sud, Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Physiopathologie Toulouse Purpan (ex IFR 30 et IFR 150), Université Toulouse III - Paul Sabatier ( UPS ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-IFR30-IFR150-Institut National de la Santé et de la Recherche Médicale ( INSERM ), IFR Necker-Enfants Malades ( IRNEM ), Assistance publique - Hôpitaux de Paris (AP-HP)-Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hôpital Sud, Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140-Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Università Cattolica del Sacro Cuore, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré, and Hôpital Jeanne de Flandre [Lille]-Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille )
Subjects: Male, MESH: Fatal Outcome, MESH : Molecular Sequence Data, MESH: Anophthalmos, [SDV.GEN] Life Sciences [q-bio]/Genetics, MESH: Amino Acid Sequence, Settore MED/03 - GENETICA MEDICA, MESH : Syndrome, Fatal Outcome, MESH : Female, MESH: Syndrome, [SDV.BDD]Life Sciences [q-bio]/Development Biology, MESH : Sequence Alignment, MESH : Amino Acid Sequence, MESH : Infant, Syndrome, MESH : Adult, MESH: Infant, MESH : Phenotype, Phenotype, Female, MESH: Membrane Proteins, MESH : Mutation, Adult, MESH: Abnormalities, Multiple, MESH: Mutation, stra6, MESH : Male, Molecular Sequence Data, MESH: Sequence Alignment, MESH: Phenotype, [SDV.BDD] Life Sciences [q-bio]/Development Biology, Humans, Abnormalities, Multiple, Amino Acid Sequence, [ SDV.BDD ] Life Sciences [q-bio]/Development Biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, MESH: Molecular Sequence Data, MESH: Humans, MESH : Abnormalities, Multiple, MESH : Humans, MESH : Anophthalmos, Anophthalmos, Infant, Membrane Proteins, MESH: Adult, MESH: Male, MESH : Fatal Outcome, MESH : Membrane Proteins, Mutation, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, Sequence Alignment, MESH: Female
Abstract: International audience; Matthew-Wood, Spear, PDAC or MCOPS9 syndrome are alternative names used to refer to combinations of microphthalmia/anophthalmia, malformative cardiac defects, pulmonary dysgenesis, and diaphragmatic hernia. Recently, mutations in STRA6, encoding a membrane receptor for vitamin A-bearing plasma retinol binding protein, have been identified in such patients. We performed STRA6 molecular analysis in three fetuses and one child diagnosed with Matthew-Wood syndrome and in three siblings where two adult living brothers are affected with combinations of clinical anophthalmia, tetralogy of Fallot, and mental retardation. Among these patients, six novel mutations were identified, bringing the current total of known STRA6 mutations to seventeen. We extensively reviewed clinical data pertaining to all twenty-one reported patients with STRA6 mutations (the seven of this report and fourteen described elsewhere) and discuss additional features that may be part of the syndrome. The clinical spectrum associated with STRA6 deficiency is even more variable than initially described.
Published: 2009
Full Text: View/download PDF

33. CX(3)CR1(+) CD115(+) CD135(+) common macrophage/DC precursors and the role of CX(3)CR1 in their response to inflammation

Author: Cédric Auffray, Ana Cumano, Grégoire Lauvau, Laura Campisi, Frederic Geissmann, Darin K. Fogg, Thierry Jo Molina, David A. Hume, Céline Trouillet, Brigitte Senechal, Julia Leemput, Karine Bigot, Emilie Narni-Mancinelli, Marc Abitbol, Noah Saederup, Israel F. Charo, Système des phagocytes mononucléés et immunopathologie, Université Paris Descartes - Paris 5 (UPD5), Immunologie des maladies infectieuses allergiques et autoimmunes, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre for Cellular and Molecular Biology of Inflammation, King‘s College London, Gladstone Institute of Cardiovascular Disease, University of California [San Francisco] (UC San Francisco), University of California (UC)-University of California (UC), Centre d'étude et de recherche thérapeutiques en ophtalmologie, The Roslin Institute and Royal (Dick) School of Veterinary Studies, University of Edinburgh, Développement des Lymphocytes, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), This work was supported by an European Young Investigator (EURYI) award to F. Geissmann, grants from Institut National de la Sant é et de la Recherche M é dicale (Avenir) and Human Frontier Science Program (CDA) to G. Lauvau, grants from the Agence Nationale de la Recherche (ANR IRAP2005) to F. Geissmann and G. Lauvau, and grants from the Fondation pour la Recherche Medicale to F. Geissmann (Equipe FRM 2006) and to G. Lauvau (FRM equipments fund)., Université Nice Sophia Antipolis (... - 2019) (UNS), University of California [San Francisco] (UCSF), University of California-University of California, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Vougny, Marie-Christine, Université Paris Descartes - Paris 5 ( UPD5 ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), University of California [San Francisco] ( UCSF ), and Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM )
Subjects: MESH: Inflammation, Monocytes/cytology, MESH: Spleen, MESH: Monocytes, MESH: Listeria monocytogenes, Monocytes, Mice, 0302 clinical medicine, Cell Movement, Spleen/cytology, MESH : Cell Proliferation, MESH : Cell Movement, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Macrophage, MESH: Animals, MESH: Cell Movement, MESH : Macrophages, MESH : Cell Survival, 0303 health sciences, MESH: Bone Marrow Cells, Stem Cells, hemic and immune systems, Dendritic Cells/enzymology, Receptors, Chemokine/metabolism, 3. Good health, Cell biology, MESH : Phenotype, MESH: Cell Survival, Tumor necrosis factor alpha, Receptors, Chemokine, MESH : Cell Differentiation, MESH: fms-Like Tyrosine Kinase 3, MESH: Receptor, Macrophage Colony-Stimulating Factor, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, CX3C Chemokine Receptor 1, Bone Marrow Cells/cytology, Tumor Necrosis Factor-alpha/biosynthesis, Spleen, Dendritic Cells/cytology, MESH: Phenotype, Article, 03 medical and health sciences, Receptor, Macrophage Colony-Stimulating Factor/metabolism, MESH : Inflammation, fms-Like Tyrosine Kinase 3/metabolism, Tumor Necrosis Factor-alpha, MESH : Listeria Infections, Macrophages, Monocytes/immunology, Dendritic cell, Dendritic Cells, Listeria monocytogenes, fms-Like Tyrosine Kinase 3, Dendritic Cells/immunology, MESH : Dendritic Cells, MESH: Tumor Necrosis Factor-alpha, Reactive Oxygen Species, MESH : Bone Marrow Cells, Myeloid, MESH : Reactive Oxygen Species, Nitric Oxide Synthase Type II, Macrophages/immunology, Inflammation/enzymology, Immunology and Allergy, Listeriosis, MESH : Tumor Necrosis Factor-alpha, MESH: Dendritic Cells, MESH: Reactive Oxygen Species, Cell Differentiation, Inflammation/immunology, Listeriosis/immunology, medicine.anatomical_structure, Phenotype, MESH : Stem Cells, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Nitric Oxide Synthase Type II, medicine.symptom, Stem cell, MESH: Listeria Infections, Nitric Oxide Synthase Type II/metabolism, MESH : Spleen, MESH: Cell Differentiation, MESH : Receptors, Chemokine, MESH : fms-Like Tyrosine Kinase 3, Cell Survival, Macrophages/enzymology, Inflammation, Bone Marrow Cells, Receptor, Macrophage Colony-Stimulating Factor, MESH: Stem Cells, Biology, MESH : Receptor, Macrophage Colony-Stimulating Factor, Reactive Oxygen Species/metabolism, MESH: Cell Proliferation, MESH : Mice, medicine, Animals, MESH: Mice, 030304 developmental biology, Cell Proliferation, MESH: Macrophages, Macrophages/cytology, MESH : Nitric Oxide Synthase Type II, Receptors, Chemokine/deficiency, MESH : Monocytes, Fms-Like Tyrosine Kinase 3, MESH : Animals, MESH : Listeria monocytogenes, MESH: Receptors, Chemokine, Bone Marrow Cells/immunology, 030215 immunology
Abstract: International audience; CX(3)CR1 expression is associated with the commitment of CSF-1R(+) myeloid precursors to the macrophage/dendritic cell (DC) lineage. However, the relationship of the CSF-1R(+) CX(3)CR1(+) macrophage/DC precursor (MDP) with other DC precursors and the role of CX(3)CR1 in macrophage and DC development remain unclear. We show that MDPs give rise to conventional DCs (cDCs), plasmacytoid DCs (PDCs), and monocytes, including Gr1(+) inflammatory monocytes that differentiate into TipDCs during infection. CX(3)CR1 deficiency selectively impairs the recruitment of blood Gr1(+) monocytes in the spleen after transfer and during acute Listeria monocytogenes infection but does not affect the development of monocytes, cDCs, and PDCs.
Published: 2009
Full Text: View/download PDF

34. The FBN2 gene: new mutations, locus-specific database (Universal Mutation Database FBN2), and genotype-phenotype correlations

Author: Christine Binquet, Christine Monino, Laurence Faivre, Gwenaëlle Collod-Béroud, Dalil Hamroun, Guillaume Jondeau, Christophe Béroud, Luitgard M. Neumann, Prateek Gupta, Catherine Boileau, Mireille Claustres, Dianna M. Milewicz, Elodie Gautier, Maurice Godfrey, Christoph Marschall, Hanns Georg Klein, Cheryl L. Maslen, Mélissa Yana Frédéric, Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques, Université Montpellier 1 ( UM1 ) -IFR3-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Center for Human Genetics and Laboratory Medicine, Center of Human Genetics and Laboratory Medicine, Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service de cardiologie, Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Consultation Marfan, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bichat, Hémostase, bio-ingénierie et remodelage cardiovasculaires ( LBPC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris 13 ( UP13 ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Galilée, Charité Campus Virchow-Klinikum (CVK), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques ( CIC-EC ), Université de Bourgogne ( UB ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Department of Molecular and Medical Genetics, Oregon Health and Science University, Center for Human Molecular Genetics, University of Nebraska Omaha, Department of Internal Medicine and Neurosurgery, The University of Texas Medical School, Service de biochimie, d'hormonologie et de génétique moléculaire, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, UFR Paris-Ile-de-France-Ouest (PIFO), Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Montpellier 1, INSERM, GIS-Institut des Maladies Rares 2004, Contract grant sponsor: Association Française contre les Myopathies (AFM), Grant number: AFM-R07017FF, Contract grant sponsor: Agence Nationale pour la Recherche (ANR), Grant number: ANR-05PCOD-14-02., 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 Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bichat, Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Oregon Health and Science University [Portland] (OHSU), University of Nebraska System-University of Nebraska System, Service de biochimie, d'hormonologie et de génétique moléculaire [CHU Amrboise Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), COLLOD-BEROUD, Gwenaëlle, IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Galilée, and University of Nebraska [Omaha]
Subjects: Fibrillin-2, MESH : Polymorphism, Genetic, Fibrillin-1, DNA Mutational Analysis, MESH : Genotype, [SDV.GEN] Life Sciences [q-bio]/Genetics, computer.software_genre, MESH: Genotype, 0302 clinical medicine, Genotype, Databases, Genetic, Missense mutation, Congenital contractural arachnodactyly, MESH: DNA Mutational Analysis, Genetics (clinical), MESH: Databases, Genetic, Regulation of gene expression, Genetics, 0303 health sciences, Database, MESH : Gene Expression Regulation, Microfilament Proteins, Phenotype, MESH: Gene Expression Regulation, Beals-Hecht syndrome, 3. Good health, INC, MESH : Phenotype, MESH : Mutation, Fibrillin, musculoskeletal diseases, MESH: Mutation, MESH : Microfilament Proteins, database OFFICIAL JOURNAL wwwhgvsorg & 2008 WILEY-LISS, Locus (genetics), fibrillin, MESH : DNA Mutational Analysis, Biology, Fibrillins, MESH: Phenotype, MESH: Sequence Homology, Nucleic Acid, congenital contractural arachnodactyly, 03 medical and health sciences, MESH: Microfilament Proteins, Sequence Homology, Nucleic Acid, MESH: Polymorphism, Genetic, medicine, Humans, MESH : Sequence Homology, Nucleic Acid, FBN2, CCA, MESH : Databases, Genetic, Gene, 030304 developmental biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, Polymorphism, Genetic, MESH: Humans, MESH : Humans, medicine.disease, Gene Expression Regulation, Mutation, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, computer, 030217 neurology & neurosurgery
Abstract: International audience; Congenital contractural arachnodactyly (CCA) is an extremely rare disease, due to mutations in the FBN2 gene encoding fibrillin-2. Another member of the fibrillin family, the FBN1 gene, is involved in a broad phenotypic continuum of connective-tissue disorders including Marfan syndrome. Identifying not only what is in common but also what differentiates these two proteins should enable us to better comprehend their respective functions and better understand the multitude of diseases in which these two genes are involved. In 1995 we created a locus-specific database (LSDB) for FBN1 mutations with the Universal Mutation Database (UMD) tool. To facilitate comparison of identified mutations in these two genes and search for specific functional areas, we created an LSDB for the FBN2 gene: the UMD-FBN2 database. This database lists 26 published and six newly identified mutations that mainly comprise missense and splice-site mutations. Although the number of described FBN2 mutations was low, the frequency of joint dislocation was significantly higher with missense mutations when compared to splice site mutations.
Published: 2009
Full Text: View/download PDF

35. Biofilm-detached cells, a transition from a sessile to a planktonic phenotype: a comparative study of adhesion and physiological characteristics in Pseudomonas aeruginosa

Author: Rollet, Cécile, Gal, Laurent, Guzzo, Jean, Laboratoire de Recherche en Vigne et Vin (REVV), AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB), Microbiologie du Sol et de l'Environnement (MSE), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Institut Universitaire de la Vigne et du Vin 'Jules Guyot' (IUVV Jules Guyot), Université de Bourgogne (UB), Laboratoire de Recherche en Vigne et Vin ( REVV ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Microbiologie du Sol et de l'Environnement ( MSE ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ), and Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement
Subjects: MESH : Bacterial Adhesion, fungi, MESH: Biofilms, MESH : Pseudomonas aeruginosa, [ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, biochemical phenomena, metabolism, and nutrition, MESH: Phenotype, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Bacterial Adhesion, Anti-Bacterial Agents, MESH : Phenotype, Phenotype, MESH : Biofilms, Biofilms, MESH: Anti-Bacterial Agents, Pseudomonas aeruginosa, MESH: Pseudomonas aeruginosa, MESH: Bacterial Adhesion, MESH : Anti-Bacterial Agents
Abstract: International audience; Pseudomonas aeruginosa is a pathogenic bacterium widely investigated for its high incidence in clinical environments and its ability to form strong biofilms. During biofilm development, sessile cells acquire physiological characteristics differentiating them from planktonic cells. But after treatment with disinfectants, or to ensure survival of the species in hostile environments, biofilm cells can detach. This complicates disinfection procedures. This study aimed to physiologically characterize cells detached from a P. aeruginosa biofilm and to compare them with their sessile and planktonic counterparts. We first tested planktonic growth kinetics and capacities to form new biofilms. Then we investigated cell-surface properties. And finally, we tested in vitro susceptibility to antibiotics. The results first indicated that sessile and detached cells have similar planktonic growth kinetics and cell-surface properties, distinguishable from those of planktonic cells. Interestingly, the three populations exhibited different biofilm-forming capacities, suggesting that there is a transitional phenotype between sessile and planktonic states, at least during the first hours following cell detachment. It is important to consider this observation when developing treatments to optimize disinfection processes. Surprisingly, the three populations showed the same antibiotic susceptibility profile.
Published: 2009
Full Text: View/download PDF

36. Efficient intrathymic gene transfer following in situ administration of a rAAV serotype 8 vector in mice and nonhuman primates

Author: Naomi Taylor, Chantal Jacquet, David Klatzmann, Valérie S. Zimmermann, Yan Cherel, Laurence Dubreil, Rita Vicente, Guillaume Podevin, Philippe Moullier, Jack-Yves Deschamps, Oumeya Adjali, Aurélie Moreau, Vecteurs viraux et transfert de gènes in vivo, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Department of Biochemistry, University of Coimbra [Portugal] (UC), Developpement et Pathologie du Tissu Musculaire (DPTM), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Nantes, Service de chirurgie infantile, Biologie et thérapeutique des pathologies immunitaires (BTPI), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Department of Molecular Genetics and Microbiology, University of Florida [Gainesville], Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Développement et Pathologie du Tissu Musculaire (DPTM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Department of Molecular Genetics and Microbiology [Gainesville] (UF|MGM), Department of Medicine [Gainesville] (UF|Medicine), University of Florida [Gainesville] (UF)-University of Florida [Gainesville] (UF), Université de Nantes ( UN ) -IFR26-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut de Génétique Moléculaire de Montpellier ( IGMM ), Université de Montpellier ( UM ) -Centre National de la Recherche Scientifique ( CNRS ), University of Coimbra [Portugal] ( UC ), Developpement et Pathologie du Tissu Musculaire ( DPTM ), Institut National de la Recherche Agronomique ( INRA ) -Ecole Nationale Vétérinaire de Nantes, Biologie et thérapeutique des pathologies immunitaires ( BTPI ), and Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS )
Subjects: MESH : Cell Line, Cellular differentiation, MESH: Dependovirus, Transduction (genetics), Mice, 0302 clinical medicine, MESH: Genetic Vectors, Cell Movement, Drug Discovery, MESH : Cell Movement, MESH: Animals, Viral, Transgenes, MESH: Cell Movement, 0303 health sciences, Genome, MESH: Kinetics, MESH : Dependovirus, Cell Differentiation, Dependovirus, MESH : Genetic Vectors, Thymocyte, MESH : Phenotype, Phenotype, MESH : Macaca fascicularis, 030220 oncology & carcinogenesis, Molecular Medicine, MESH : Transgenes, MESH : Kinetics, MESH: Genome, Viral, MESH : Cell Differentiation, MESH : Genome, Viral, MESH: Cell Differentiation, Transgene, Genetic Vectors, [ SDV.IMM.IMM ] Life Sciences [q-bio]/Immunology/Immunotherapy, MESH: Transgenes, Genome, Viral, Thymus Gland, Biology, MESH: Phenotype, Virus, Viral vector, Cell Line, 03 medical and health sciences, In vivo, MESH : Mice, Genetics, Animals, Humans, MESH : Thymus Gland, Molecular Biology, MESH: Mice, 030304 developmental biology, Pharmacology, MESH: Humans, MESH : Humans, MESH: Thymus Gland, [SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy, Original Articles, Molecular biology, MESH: Cell Line, Kinetics, Macaca fascicularis, MESH: Macaca fascicularis, Cell culture, MESH : Animals
Abstract: International audience; The thymus is the primary site of T-cell development and plays a key role in the induction of self-tolerance. We previously showed that the intrathymic (i.t.) injection of a transgene-expressing lentiviral vector (LV) in mice can result in the correction of a T cell-specific genetic defect. Nevertheless, the efficiency of thymocyte transduction did not exceed 0.1-0.3% and we were unable to detect any thymus transduction in macaques. As such, we initiated studies to assess the capacity of recombinant adeno-associated virus (rAAV) vectors to transduce murine and primate thymic cells. In vivo administration of AAV serotype 2-derived single-stranded AAV (ssAAV) and self-complementary AAV (scAAV) vectors pseudotyped with capsid proteins of serotypes 1, 2, 4, 5, and 8 demonstrated that murine thymus transduction was significantly enhanced by scAAV2/8. Transgene expression was detected in 5% of thymocytes and, notably, transduced cells represented 1% of peripheral T lymphocytes. Moreover, i.t. administration of scAAV2/8 particles in macaques, by endoscopic-mediated guidance, resulted in significant gene transfer. Thus, in healthy animals, where thymic gene transfer does not provide a selective advantage, scAAV2/8 is a unique tool promoting the in situ transduction of thymocytes with the subsequent export of gene-modified lymphocytes to the periphery.
Published: 2008
Full Text: View/download PDF

37. Identification of 23 TGFBR2 and 6 TGFBR1 gene mutations and genotype-phenotype investigations in 457 patients with Marfan syndrome type I and II, Loeys-Dietz syndrome and related disorders

Author: Clarisse Baumann, Henri Plauchu, Didier Lacombe, Valérie Cormier-Daire, Marc Sznajder, Guillaume Jondeau, Stanislas Lyonnet, Chantal Stheneur, Bertrand Moura, Catherine Boileau, Mireille Claustres, Gwenaëlle Collod-Béroud, Christine Muti, Bertrand Chevallier, Claudine Junien, Marlène Rio, David Attias, Laurence Faivre, Laurent Gouya, Gilles Sultan, Jean-Marie Le Parc, Service de pédiatrie, urgences enfants, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, Consultation Marfan, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Bichat, Physiologie Cellulaire des Regulations Hormonales, Nutritionnelles et Pharmacologiques, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques, Université Montpellier 1 ( UM1 ) -IFR3-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques ( CIC-EC ), Université de Bourgogne ( UB ) -Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de génétique - Centre de référence des maladies rares, anomalies du développement et syndromes malformatifs (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service de biochimie, d'hormonologie et de génétique moléculaire, UFR Paris-Ile-de-France-Ouest, Université de Versailles Saint-Quentin-en-Yvelines ( UVSQ ), Interactions de l'épithelium intestinal avec le système immunitaire, Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'ophtalmologie, Service de Rhumatologie, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Ambroise Paré, Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement ( Inserm U781 ), Département de Génétique Médicale, Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré, Service de Génétique Médicale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-Hopital Necker-Enfants Malades, Service de Génétique, Hôtel Dieu, Service de génétique médicale, Université de Bordeaux ( UB ) -CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de cardiologie, Assistance publique - Hôpitaux de Paris (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris]-Université Paris Diderot - Paris 7 ( UPD7 ), Hémostase, bio-ingénierie et remodelage cardiovasculaires ( LBPC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris 13 ( UP13 ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Galilée, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ) - Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Ambroise Paré, Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Bichat, Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), Université Montpellier 1 (UM1) - IFR3 - Institut National de la Santé et de la Recherche Médicale (INSERM) - Université de Montpellier (UM), Centre d'Investigation Clinique 1432 (Dijon) - Epidemiologie Clinique/Essais Cliniques (CIC-EC), Université de Bourgogne (UB) - Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon) - Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université Paris Descartes - Paris 5 (UPD5) - Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Ambroise Paré, Laboratoire de Génétique Moléculaire, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier) - Hôpital Arnaud de Villeneuve, Handicaps génétiques de l'enfant, Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Robert Debré, Assistance publique - Hôpitaux de Paris (AP-HP) - Hopital Necker-Enfants Malades, Université de Bordeaux (UB) - CHU Bordeaux [Bordeaux] - Groupe hospitalier Pellegrin, Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Bichat - Claude Bernard [Paris] - Université Paris Diderot - Paris 7 (UPD7), Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), Université Paris 13 (UP13) - Université Paris Diderot - Paris 7 (UPD7) - Université Sorbonne Paris Cité (USPC) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Institut Galilée, Service de pédiatrie, urgences enfants [CHU Ambroise-Paré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Ambroise Paré [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bichat, Pharmacologie, toxicologie et signalisation cellulaire (U747), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de biochimie, d'hormonologie et de génétique moléculaire [CHU Amrboise Paré], 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), Service d'ophtalmologie [CHU Ambroise Paré], Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Galilée, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), COLLOD-BEROUD, Gwenaëlle, Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), and Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Proband, Marfan syndrome, Pathology, MESH : Receptors, Transforming Growth Factor beta, MESH : Polymorphism, Genetic, DNA Mutational Analysis, Receptor, Transforming Growth Factor-beta Type I, MESH : Genotype, [SDV.GEN] Life Sciences [q-bio]/Genetics, 030204 cardiovascular system & hematology, Gene mutation, MESH : Child, Preschool, Loeys–Dietz syndrome, MESH : Syndrome, MESH: Genotype, Aortic aneurysm, 0302 clinical medicine, MESH : Child, MESH: Child, Genotype, MESH: Syndrome, MESH : Female, MESH: DNA Mutational Analysis, Child, Genetics (clinical), TGFBR1, TAAD, 0303 health sciences, MESH: Middle Aged, MESH : Aortic Aneurysm, Thoracic, MESH: Infant, Newborn, MESH : Infant, Syndrome, Middle Aged, MESH : Adult, Phenotype, MESH: Infant, MESH: Amino Acid Substitution, 3. Good health, TGFBR2, genotype-phenotype, MESH : Phenotype, Child, Preschool, MESH: Aortic Aneurysm, Thoracic, Female, MESH: Receptors, Transforming Growth Factor beta, MESH : Mutation, Adult, MESH : Protein-Serine-Threonine Kinases, medicine.medical_specialty, MESH: Abnormalities, Multiple, MESH: Mutation, Adolescent, MESH : Male, MESH : DNA Mutational Analysis, Protein Serine-Threonine Kinases, Biology, MESH: Phenotype, MESH : Infant, Newborn, MESH: Protein-Serine-Threonine Kinases, MESH: Marfan Syndrome, 03 medical and health sciences, MESH : Amino Acid Substitution, MESH : Adolescent, MESH: Polymorphism, Genetic, Genetics, medicine, Humans, Abnormalities, Multiple, MESH : Middle Aged, Gene, 030304 developmental biology, MESH: Adolescent, [SDV.GEN]Life Sciences [q-bio]/Genetics, Loeys-Dietz Syndrome, Polymorphism, Genetic, MESH: Humans, MESH : Marfan Syndrome, Aortic Aneurysm, Thoracic, MESH : Abnormalities, Multiple, MESH: Child, Preschool, MESH : Humans, Infant, Newborn, Receptor, Transforming Growth Factor-beta Type II, Infant, MESH: Adult, medicine.disease, MESH: Male, Amino Acid Substitution, Mutation, [ SDV.GEN ] Life Sciences [q-bio]/Genetics, Receptors, Transforming Growth Factor beta, MESH: Female
Abstract: International audience; TGFBR1 and TGFBR2 gene mutations have been associated with Marfan syndrome types 1 and 2, Loeys-Dietz syndrome and isolated familial thoracic aortic aneurysms or dissection. In order to investigate the molecular and clinical spectrum of TGFBR2 mutations we screened the gene in 457 probands suspected of being affected with Marfan syndrome or related disorders that had been referred to our laboratory for molecular diagnosis. We identified and report 23 mutations and 20 polymorphisms. Subsequently, we screened the TGFBR1 gene in the first 74 patients for whom no defect had been found, and identified 6 novel mutations and 12 polymorphisms. Mutation-carrying probands displayed at referral a large clinical spectrum ranging from the Loeys-Dietz syndrome and neonatal Marfan syndrome to isolated aortic aneurysm. Furthermore, a TGFBR1 gene mutation was found in a Shprintzen-Goldberg syndrome patient. Finally, we observed that the yield of mutation detection within the two genes was very low : 4.8% for classical MFS, 4.6% for incomplete MFS and 1% for TAAD in the TGFBR2 gene; 6.2%, 6.2% and 7% respectively in the TGFBR1 gene; in contrast to LDS, where the yield was exceptionally high (87.5%).
Published: 2008
Full Text: View/download PDF

38. Evidence of a dosage effect and a physiological endplate acetylcholinesterase deficiency in the first mouse models mimicking Schwartz-Jampel syndrome neuromyotonia

Author: Morgane Stum, Arnaud Ferry, Frédédrique Rene, Christophe Marcel, Andoni Echaniz-Laguna, Véronique Bernard, Claire-Sophie Davoine, Bertrand Fontaine, Eric Krejci, Sophie Nicole, Alban Vignaud, Marie Bangratz, Emmanuelle Girard, Jordi Molgó, Marc Herbin, Affections de la Myeline et des Canaux Ioniques Musculaires, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de neurobiologie cellulaire et moléculaire (NBCM), Centre National de la Recherche Scientifique (CNRS), Institut de Neurobiologie Alfred Fessard (INAF), Biologie des Jonctions Neuromusculaires Normales et Pathologiques (U686), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Mécanismes adaptatifs : des organismes aux communautés (MAOAC), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Groupe Myologie, 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)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de signalisation moléculaire et neurodégénerescence, Université Louis Pasteur - Strasbourg I-IFR37-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Neurologie, Hôpital Civil de Strasbourg, CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Fédération des Maladies du Système Nerveux, 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Muséum national d'Histoire naturelle (MNHN)-Collège de France (CdF)-Centre National de la Recherche Scientifique (CNRS), 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) (APHP)-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)-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) (APHP)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Pitié-Salpêtrière [APHP], Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ), Laboratoire de neurobiologie cellulaire et moléculaire ( NBCM ), Centre National de la Recherche Scientifique ( CNRS ), Institut de Neurobiologie Alfred Fessard ( INAF ), Biologie des Jonctions Neuromusculaires Normales et Pathologiques ( U686 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Mécanismes adaptatifs : des organismes aux communautés ( MAOAC ), Muséum National d'Histoire Naturelle ( MNHN ) -Collège de France ( CdF ) -Centre National de la Recherche Scientifique ( CNRS ), 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)-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 ) -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)-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 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Louis Pasteur - Strasbourg I-IFR37-Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Pitié-Salpêtrière [APHP]
Subjects: Male, Neuromyotonia, MESH: Mice, Mutant Strains, MESH: Muscle Contraction, Gene Dosage, medicine.disease_cause, MESH: Gene Dosage, MESH: Motor Endplate, chemistry.chemical_compound, Mice, 0302 clinical medicine, Missense mutation, MESH : Female, MESH : Gene Dosage, MESH: Animals, Genetics (clinical), 0303 health sciences, Mutation, biology, General Medicine, Acetylcholinesterase, MESH : Mice, Transgenic, MESH : Phenotype, medicine.anatomical_structure, Phenotype, MESH : Electromyography, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], MESH : Heparan Sulfate Proteoglycans, Muscle Contraction, medicine.medical_specialty, MESH : Isaacs Syndrome, MESH: Mice, Transgenic, MESH : Male, Schwartz–Jampel syndrome, Mutation, Missense, Mice, Transgenic, MESH : Mice, Inbred C57BL, Perlecan, Osteochondrodysplasias, MESH: Phenotype, Motor Endplate, Neuromuscular junction, MESH : Acetylcholinesterase, MESH: Electromyography, 03 medical and health sciences, In vivo, MESH: Mice, Inbred C57BL, Internal medicine, MESH : Mice, Genetics, medicine, Animals, Humans, MESH: Isaacs Syndrome, Molecular Biology, MESH: Mice, Alleles, 030304 developmental biology, MESH : Osteochondrodysplasias, MESH: Mutation, Missense, MESH: Humans, Electromyography, MESH: Alleles, MESH : Humans, MESH : Motor Endplate, MESH: Acetylcholinesterase, medicine.disease, MESH: Osteochondrodysplasias, MESH : Disease Models, Animal, Mice, Mutant Strains, MESH: Male, MESH : Mice, Mutant Strains, Mice, Inbred C57BL, Disease Models, Animal, stomatognathic diseases, Endocrinology, chemistry, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], biology.protein, MESH: Heparan Sulfate Proteoglycans, MESH : Muscle Contraction, MESH : Animals, Isaacs Syndrome, MESH: Disease Models, Animal, MESH : Alleles, MESH: Female, MESH : Mutation, Missense, 030217 neurology & neurosurgery, Heparan Sulfate Proteoglycans
Abstract: International audience; Schwartz-Jampel syndrome (SJS) is a recessive neuromyotonia with chondrodysplasia. It results from hypomorphic mutations of the gene encoding perlecan, leading to a decrease in the levels of this heparan sulphate proteoglycan in basement membranes (BMs). It has been suggested that SJS neuromyotonia may result from endplate acetylcholinesterase (AChE) deficiency, but this hypothesis has never been investigated in vivo due to the lack of an animal model for neuromyotonia. We used homologous recombination to generate a knock-in mouse strain with one missense substitution, corresponding to a human familial SJS mutation (p.C1532Y), in the perlecan gene. We derived two lines, one with the p.C1532Y substitution alone and one with p.C1532Y and the selectable marker Neo, to down-regulate perlecan gene activity and to test for a dosage effect of perlecan in mammals. These two lines mimicked SJS neuromyotonia with spontaneous activity on electromyogramm (EMG). An inverse correlation between disease severity and perlecan secretion in the BMs was observed at the macroscopic and microscopic levels, consistent with a dosage effect. Endplate AChE levels were low in both lines, due to synaptic perlecan deficiency rather than major myofibre or neuromuscular junction disorganization. Studies of muscle contractile properties showed muscle fatigability at low frequencies of nerve stimulation and suggested that partial endplate AChE deficiency might contribute to SJS muscle stiffness by potentiating muscle force. However, physiological endplate AChE deficiency was not associated with spontaneous activity at rest on EMG in the diaphragm, suggesting that additional changes are required to generate such activity characteristic of SJS.
Published: 2008
Full Text: View/download PDF

39. [Racing mania does not exist any more, manic-depressive psychosis even more so. How about schizophrenia?]

Author: Sechter , D., Haffen , E., Loo , H., Laboratoire de Neurosciences Intégratives et Cliniques - UFC (EA 481) (NEURO), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire de Neurosciences Intégratives et Cliniques - UFC ( NEURO ), and Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC )
Subjects: Periodicity, MESH: Periodicity, Bipolar Disorder, MESH: Depressive Disorder, Major, MESH: Phenotype, MESH : Schizophrenia, MESH : Schizophrenic Psychology, MESH: Bipolar Disorder, Humans, MESH : Bipolar Disorder, ComputingMilieux_MISCELLANEOUS, Depressive Disorder, Major, MESH: Humans, MESH : Humans, MESH: Affect, MESH : Affect, MESH: Schizophrenia, MESH : Phenotype, Affect, Phenotype, MESH : Periodicity, [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Schizophrenia, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Schizophrenic Psychology, MESH : Depressive Disorder, Major, MESH: Schizophrenic Psychology
Abstract: International audience
Published: 2008
Full Text: View/download PDF

40. A novel dysfunctional LHX4 mutation with high phenotypical variability in patients with hypopituitarism

Author: Thierry Brue, Frédérique Albarel, Rachel Reynaud, Alexandru Saveanu, Raja Brauner, Marie-Helene Quentien, M. El Kholy, Alain Enjalbert, Anne-Marie Guedj, N. Kaffel, Anne Barlier, Frederic Castinetti, M. Amin, A. Buffin, Centre de recherche en neurobiologie - neurophysiologie de Marseille (CRN2M), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Interactions cellulaires neuroendocriniennes (ICN), Université de la Méditerranée - Aix-Marseille 2-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Aix Marseille Université (AMU) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Centre National de la Recherche Scientifique (CNRS), and Université de la Méditerranée - Aix-Marseille 2 - Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, MESH : Transcription Factors, MESH: Introns, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Electrophoretic Mobility Shift Assay, MESH : Genotype, Hypopituitarism, medicine.disease_cause, MESH: Hypopituitarism, Biochemistry, MESH: Genotype, 0302 clinical medicine, Endocrinology, MESH : Female, MESH : Homeodomain Proteins, Pituitary stalk, 0303 health sciences, Mutation, MESH: Middle Aged, MESH : Hypopituitarism, MESH: Transcription Factors, Middle Aged, MESH : Adult, Pedigree, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 3. Good health, MESH : Phenotype, Phenotype, medicine.anatomical_structure, Sella turcica, MESH : Electrophoretic Mobility Shift Assay, Female, MESH : Mutation, Adult, medicine.medical_specialty, MESH: Mutation, Genotype, Somatotropic cell, MESH: Pedigree, MESH : Male, LIM-Homeodomain Proteins, 030209 endocrinology & metabolism, Context (language use), Biology, MESH: Phenotype, MESH : Introns, 03 medical and health sciences, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Posterior pituitary, Internal medicine, MESH: Homeodomain Proteins, medicine, Humans, MESH : Middle Aged, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], 030304 developmental biology, Homeodomain Proteins, MESH: Humans, Biochemistry (medical), MESH : Humans, Heterozygote advantage, MESH: Adult, medicine.disease, Introns, MESH: Male, MESH : Pedigree, MESH: Electrophoretic Mobility Shift Assay, MESH: Female, Transcription Factors
Abstract: International audience; CONTEXT: LHX4 is a LIM homeodomain transcription factor involved in pituitary ontogenesis. Only a few heterozygous LHX4 mutations have been reported to be responsible for congenital pituitary hormone deficiency. SUBJECTS AND METHODS: A total of 136 patients with congenital hypopituitarism associated with malformations of brain structures, pituitary stalk, or posterior pituitary gland was screened for LHX4 mutations. RESULTS: Three novel allelic variants that cause predicted changes in the protein sequence of LHX4 (2.3%) were found (p.Thr99fs, p.Thr90Met, and p.Gly370Ser). On the basis of functional studies, p.Thr99fs mutation was responsible for the patients' phenotype, whereas p.Thr90Met and p.Gly370Ser were likely polymorphisms. Patients bearing the heterozygous p.Thr99fs mutation had variable phenotypes: two brothers presented somato-lactotroph and thyrotroph deficiencies, with pituitary hypoplasia and poorly developed sella turcica; the youngest brother (propositus) also had corpus callosum hypoplasia and ectopic neurohypophysis; their father only had somatotroph deficiency and delayed puberty with pituitary hyperplasia. Functional studies showed that the mutation induced a complete loss of transcriptional activity on POU1F1 promoter and a lack of DNA binding. Cotransfection of p.Thr99fs mutant and wild-type LHX4 failed to evidence any dominant negative effect, suggesting a mechanism of haploinsufficiency. We also identified prolactin and GH promoters as potential target genes of LHX4 and found that the p.Thr99fs mutant was also unable to transactivate these promoters. CONCLUSIONS: The present report describes three new exonic LHX4 allelic variants with at least one being responsible for congenital hypopituitarism. It also extends the phenotypical heterogeneity associated with LHX4 mutations, which includes variable anterior pituitary hormone deficits, as well as pituitary and extrapituitary abnormalities.
Published: 2008
Full Text: View/download PDF

41. MicroRNA profiling in hepatocellular tumors is associated with clinical features and oncogene/tumor suppressor gene mutations. : hepatocellular tumors miRNA profiling

Author: Ladeiro , Yannick, Couchy , Gabrielle, Balabaud , Charles, Bioulac-Sage , Paulette, Pelletier , Laura, Rebouissou , Sandra, Zucman-Rossi , Jessica, Genomique Fonctionnelle des Tumeurs Solides, Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ) -IFR105-Université Paris Diderot - Paris 7 ( UPD7 ), Institut Universitaire d'Hématologie ( IUH ), Université Paris Diderot - Paris 7 ( UPD7 ), Fibrose hépatique et cancer du foie, Université Bordeaux Segalen - Bordeaux 2-IFR66-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Hépato-Gastro-Entérologie, CHU Bordeaux [Bordeaux]-Hôpital Saint-André, Laboratoire d'anatomie pathologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, and This work was supported by the ANRS, Inserm (Réseaux de recherche clinique et réseaux de recherche en santé des populations), and the program 'Carte d'identité des tumeurs' initiated, developed and funded by the Ligue Nationale Contre le Cancer. YL is supported by an ANRS doctoral fellowship. JZR is supported by a 'contrat d'interface' between Inserm and CHU Bordeaux.
Subjects: MESH : Carcinoma, Hepatocellular, MESH : Liver Neoplasms, Hepatocellular carcinoma, MESH : Gene Expression Regulation, Neoplastic, MESH : Genes, Tumor Suppressor, ß-catenin, Benign and malignant tumors, liver cell adenoma, MESH : Tumor Cells, Cultured, Focal nodular hyperplasia, HBV, Alcohol consumption, miRNA, MESH : Gene Expression Profiling, MESH : Humans, biomarkers, MESH : beta Catenin, Hepatocellular adenoma, MESH : Risk Factors, HNF1a, MESH : MicroRNAs, MESH : Phenotype, HCV, MESH : Hepatocyte Nuclear Factor 1-alpha, [ SDV.MHEP.HEG ] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, MESH : Mutation, microarray, transcriptome
Abstract: International audience; Molecular classifications defining new tumor subtypes have been recently refined with genetic and transcriptomic analyses of benign and malignant hepatocellular tumors. Here, we performed microRNA (miRNA) profiling in two series of fully annotated liver tumors to uncover associations between oncogene/tumor suppressor mutations and clinical and pathological features. Expression levels of 250 miRNAs in 46 benign and malignant hepatocellular tumors were compared to those of 4 normal liver samples with quantitative reverse-transcriptase polymerase chain reaction. miRNAs associated with genetic and clinical characteristics were validated in a second series of 43 liver tumor samples and 16 nontumor samples. miRNA profiling unsupervised analysis classified samples in unique clusters characterized by histological features (tumor/nontumor, P < 0.001; benign/malignant tumors, P < 0.01; inflammatory adenoma and focal nodular hyperplasia, P < 0.01), clinical characteristics [hepatitis B virus (HBV) infection, P < 0.001; alcohol consumption, P < 0.05], and oncogene/tumor suppressor gene mutations [beta-catenin, P < 0.01; hepatocyte nuclear factor 1alpha (HNF1alpha), P < 0.01]. Our study identified and validated miR-224 overexpression in all tumors and miR-200c, miR-200, miR-21, miR-224, miR-10b, and miR-222 specific deregulation in benign or malignant tumors. Moreover, miR-96 was overexpressed in HBV tumors, and miR-126* was down-regulated in alcohol-related hepatocellular carcinoma. Down-regulations of miR-107 and miR-375 were specifically associated with HNF1alpha and beta-catenin gene mutations, respectively. miR-375 expression was highly correlated to that of beta-catenin-targeted genes as miR-107 expression was correlated to that of HNF1alpha in a small interfering RNA cell line model. Thus, this strongly suggests that beta-catenin and HNF1alpha could regulate miR-375 and miR-107 expression levels, respectively. CONCLUSION: Hepatocellular tumors may have a distinct miRNA expression fingerprint according to malignancy, risk factors, and oncogene/tumor suppressor gene alterations. Dissecting these relationships provides a new hypothesis to understand the functional impact of miRNA deregulation in liver tumorigenesis and the promising use of miRNAs as diagnostic markers.
Published: 2008
Full Text: View/download PDF

42. Impairment of CDKL5 nuclear localisation as a cause for severe infantile encephalopathy

Author: Sylvie Odent, Jamel Chelly, Christophe Philippe, Thierry Bienvenu, Haydeé Rosas-Vargas, L. Lazaro, B. Girard, C. Gitiaux, Nadia Bahi-Buisson, Juliette Nectoux, Philippe Jonveaux, M. A. N'Guyen Morel, Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Unité de génétique médicale, hôpital Sud, Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin ( UMR_S567 / UMR 8104 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital Sud, Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140-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 Descartes - Paris 5 (UPD5), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)
Subjects: MESH : RNA, Messenger, MESH: Sequence Homology, Amino Acid, Mutant, CDKL5, MESH: Brain Diseases, Metabolic, Inborn, MESH: Amino Acid Sequence, MESH : Child, Preschool, MESH: Base Sequence, medicine.disease_cause, MESH: Magnetic Resonance Imaging, 0302 clinical medicine, Missense mutation, MESH : Female, MESH: Animals, MESH: DNA Mutational Analysis, [ SDV.GEN.GH ] Life Sciences [q-bio]/Genetics/Human genetics, Genetics (clinical), Genetics, 0303 health sciences, Mutation, MESH : Cell Nucleus, MESH: X Chromosome Inactivation, MESH : Amino Acid Sequence, MESH : Infant, Phenotype, MESH: Amino Acid Substitution, MESH: Infant, Hypotonia, MESH : Sequence Homology, Amino Acid, 3. Good health, MESH: COS Cells, MESH : Phenotype, MESH : X Chromosome Inactivation, medicine.symptom, MESH : Transfection, MESH : COS Cells, MESH : Protein-Serine-Threonine Kinases, MESH: Cell Nucleus, Encephalopathy, MESH : Brain Diseases, Metabolic, Inborn, MESH : DNA Mutational Analysis, Biology, MESH: Phenotype, MESH: Protein-Serine-Threonine Kinases, 03 medical and health sciences, MESH : Amino Acid Substitution, MESH: Plasmids, MESH : Magnetic Resonance Imaging, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, MESH: Electroencephalography, medicine, Atypical Rett syndrome, MESH : Electroencephalography, 030304 developmental biology, MESH: RNA, Messenger, MESH: Mutation, Missense, MESH: Humans, MESH: Transfection, MESH : Humans, MESH: Child, Preschool, medicine.disease, MESH: Cercopithecus aethiops, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, MESH : Plasmids, MESH : Base Sequence, MESH : Animals, MESH : Cercopithecus aethiops, MESH: Female, 030217 neurology & neurosurgery, MESH : Mutation, Missense, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Mutations in the human X-linked cyclin-dependent kinase-like 5 (CDKL5) gene have been shown to cause infantile spasms as well as Rett syndrome-like phenotype. To date, fewer than 20 different mutations have been reported. So far, no clear genotype-phenotype correlation has been established. We screened the entire coding region of CDKL5 in 151 affected girls with a clinically heterogeneous phenotype ranging from encephalopathy with epilepsy to atypical Rett syndrome by denaturing high liquid performance chromatography and direct sequencing, and we identified three novel missense mutations located in catalytic domain (p.Ala40Val, p.Arg65Gln, p.Leu220Pro). Segregation analysis showed that p.Arg65Gln was inherited from the healthy father, which rules out the involvement of CDKL5 in the aetiology of the phenotype in this patient. However, the de novo occurrence was shown for p.Ala40Val and p.Leu220Pro. The p.Ala40Val mutation was observed in two unrelated patients and represented the first recurrent mutation in the CDKL5 gene. For the two de novo mutations, we analysed the cellular localisation of the wild-type and CDKL5 mutants by transfection experiments. We showed that the two CDKL5 mutations cause mislocalisation of the mutant CDKL5 proteins in the cytoplasm. Interestingly these missense mutations that result in a mislocalisation of the CDKL5 protein are associated with severe developmental delay which was apparent within the first months of life characterised by early and generalised hypotonia, and autistic features, and as well as early infantile spasms.
Published: 2008
Full Text: View/download PDF

43. Extraintestinal virulence is a coincidental by-product of commensalism in B2 phylogenetic group Escherichia coli strains

Author: Olivier Clermont, Stéphanie Gouriou, Olivier Tenaillon, Tony Le Gall, Bertrand Picard, Xavier Nassif, Erick Denamur, Ecologie et Evolution des Microorganismes ( EEM ), Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris 13 ( UP13 ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Génétique moléculaire et génétique épidémiologique, Université de Brest ( UBO ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de Microbiologie, Centre Hospitalier Régional Universitaire de Brest ( CHRU Brest ), Pathogénie des infections systémiques ( UMR_S 570 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Ecologie et Evolution des Microorganismes (EEM), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Pathogénie des infections systémiques (UMR_S 570), and Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Sequence Analysis, DNA, commensalism, MESH : Escherichia coli, MESH : Genotype, MESH: Virulence, [ SDV.MP.BAC ] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, MESH: Genome, Bacterial, medicine.disease_cause, MESH: Genotype, Mice, MESH : DNA, Bacterial, MESH: Animals, MESH : Female, MESH: Phylogeny, Pathogen, MESH: Evolution, Molecular, Phylogeny, 2. Zero hunger, Genetics, 0303 health sciences, Phylogenetic tree, Virulence, coincidental by-product, MESH: Escherichia coli, MESH : Genes, Bacterial, MESH : Virulence, extraintestinal virulence, 3. Good health, MESH : Phenotype, Phenotype, Female, Gene pool, MESH: Genes, Bacterial, DNA, Bacterial, Genotype, MESH : Genome, Bacterial, Biology, MESH: Phenotype, Evolution, Molecular, 03 medical and health sciences, Phylogenetics, MESH : Mice, medicine, Escherichia coli, Animals, Humans, MESH : Evolution, Molecular, MESH: Mice, Molecular Biology, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, MESH: Humans, 030306 microbiology, MESH : Humans, MESH : Phylogeny, Sequence Analysis, DNA, Commensalism, MESH: DNA, Bacterial, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Genes, Bacterial, Multilocus sequence typing, MESH : Animals, MESH: Female, Genome, Bacterial, MESH : Sequence Analysis, DNA
Abstract: This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Molecular Biology and Evolution following peer review. The definitive publisher-authenticated version Mol. Biol. Evol. 24(11):2373–2384. 2007 is available online at: http://mbe.oxfordjournals.org/content/24/11/2373.full.pdf+html.; International audience; The selective pressures leading to the evolution and maintenance of virulence in the case of facultative pathogens are quite unclear. For example, Escherichia coli, a commensal of the gut of warm-blooded animals and humans, can cause severe extraintestinal diseases, such as septicemia and meningitis, which represent evolutionary dead ends for the pathogen as they are associated to rapid host death and poor interhost transmission. Such infectious process has been linked to the presence of so-called "virulence genes." To understand the evolutionary forces that select and maintain these genes, we focused our study on E. coli B2 phylogenetic group strains that encompass both commensal and pathogenic (extra- and intraintestinal) strains. Multilocus sequence typing (MLST), comparative genomic hybridization of the B2 flexible gene pool, and quantification of extraintestinal virulence using a mouse model of septicemia were performed on a panel of 60 B2 strains chosen for their genetic and ecologic diversity. The phylogenetic history of the strains reconstructed from the MLST data indicates the emergence of at least 9 subgroups of strains. A high polymorphism is observed in the B2 flexible gene pool among the strains with a good correlation between the MLST-inferred phylogenetic history of the strains and the presence/absence of specific genomic regions, indicating coevolution between the chromosomal background and the flexible gene pool. Virulence in the mouse model is a highly prevalent and widespread character present in all subgroups except one. Association studies reveal that extraintestinal virulence is a multigenic process with a common set of "virulence determinants" encompassing genes involved in transcriptional regulation, iron metabolism, adhesion, lipopolysaccharide (LPS) biosynthesis, and the recently reported peptide polyketide hybrid synthesis system. Interestingly, these determinants can also be viewed as intestinal colonization and survival factors linked to commensalism as they can increase the fitness of the strains within the normal gut environment. Altogether, these data argue for an ancestral emergence of the extraintestinal virulence character that is a coincidental by-product of commensalism. Furthermore, the phenotypic and genotypic markers identified in this work will allow further epidemiological studies devoted to test the niche specialization hypothesis for the B2 phylogenetic subgroups.
Published: 2007
Full Text: View/download PDF

44. [Vaccine encephalopathy: a myth collapses?]

Author: Philippe, Kahane, Alexis, Arzimanoglou, Laboratoire de physiopathologie de l'épilepsie (LNPEE), CHU Grenoble, Institut Des Épilepsies de l'Enfant et de l'adolescent (CTRS-IDEE), Hospices Civils de Lyon (HCL), Service de neurologie pédiatrique et maladies métaboliques, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Deransart, Colin, Laboratoire de physiopathologie de l'épilepsie ( LNPEE ), Institut Des Épilepsies de l'Enfant et de l'adolescent ( CTRS-IDEE ), Hospices Civils de Lyon ( HCL ), and Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 ( UPD7 )
Subjects: Time Factors, Epilepsies, Myoclonic, MESH : Genotype, MESH : Child, Preschool, Sodium Channels, MESH : Syndrome, MESH: Genotype, MESH : Child, MESH: Child, MESH: Syndrome, MESH: Nerve Tissue Proteins, MESH: Encephalomyelitis, Acute Disseminated, Child, MESH : Nerve Tissue Proteins, ComputingMilieux_MISCELLANEOUS, Encephalomyelitis, Acute Disseminated, Vaccination, Age Factors, MESH: Epilepsies, Myoclonic, Electroencephalography, MESH : Infant, Syndrome, MESH: Infant, MESH : Phenotype, Phenotype, Child, Preschool, MESH : Mutation, MESH : Time Factors, MESH: Mutation, Genotype, Nerve Tissue Proteins, MESH: Phenotype, MESH: Sodium Channels, MESH : Epilepsies, Myoclonic, MESH : Sodium Channels, MESH: Electroencephalography, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH : Electroencephalography, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Age Factors, MESH : Encephalomyelitis, Acute Disseminated, MESH: Humans, MESH : Humans, MESH: Time Factors, MESH: Child, Preschool, Infant, MESH: Vaccination, NAV1.1 Voltage-Gated Sodium Channel, MESH : Vaccination, Mutation, MESH : Age Factors
Abstract: International audience
Published: 2007
Full Text: View/download PDF

45. Developmental regulation of the membrane properties of central vestibular neurons by sensory vestibular information in the mouse

Author: Eugene, D., Deforges, S., Guimont, F., Vidoux, E., Vidal, P.P., Moore, L.E., Vibert, Nicolas, Laboratoire de Neurobiologie des Réseaux Sensorimoteurs (LNRS), Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5), Department of Biomedical Engineering [Boston], Boston University [Boston] (BU), Centre de Recherches sur la Cognition et l'Apprentissage (CeRCA), Université de Poitiers-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Neurobiologie des Réseaux Sensorimoteurs ( LNRS ), Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris Descartes - Paris 5 ( UPD5 ), Boston University [Boston] ( BU ), Centre de Recherches sur la Cognition et l'Apprentissage ( CeRCA ), Université de Poitiers-Université de Tours-Centre National de la Recherche Scientifique ( CNRS ), Centre National de la Recherche Scientifique (CNRS)-Université de Tours-Université de Poitiers, and Université de Poitiers-Université de Tours-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH : RNA, Messenger, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, MESH: Head Movements, MESH: Calcium-Binding Proteins, MESH : Behavior, Animal, MESH: Chelating Agents, MESH : Parvalbumins, MESH : Calcium-Binding Proteins, MESH: Behavior, Animal, MESH: Gene Expression Regulation, Developmental, MESH : Membrane Potentials, MESH: Animals, MESH: Nerve Tissue Proteins, MESH : Potassium Channels, Voltage-Gated, MESH : Patch-Clamp Techniques, MESH : Nerve Tissue Proteins, MESH : Organ Culture Techniques, MESH : Mice, Inbred Strains, MESH: Electric Capacitance, MESH : Egtazic Acid, MESH : Calcium-Binding Protein, Vitamin D-Dependent, MESH : Mice, Transgenic, MESH : Phenotype, [ SDV.NEU.NB ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, [SCCO.PSYC]Cognitive science/Psychology, MESH: Vestibular Nuclei, MESH: Mice, Transgenic, MESH: Egtazic Acid, MESH: Phenotype, MESH: Mice, Inbred Strains, MESH : Electric Capacitance, MESH: Parvalbumins, MESH : Mice, MESH: Patch-Clamp Techniques, otorhinolaryngologic diseases, MESH: Membrane Potentials, MESH : Chelating Agents, MESH: Mice, MESH: RNA, Messenger, MESH: Age Factors, MESH: Calcium-Binding Protein, Vitamin D-Dependent, MESH : Critical Period (Psychology), MESH: Organ Culture Techniques, MESH: Hair Cells, Vestibular, MESH: Critical Period (Psychology), MESH : Head Movements, nervous system, MESH : Hair Cells, Vestibular, MESH : Age Factors, MESH : Animals, MESH : Gene Expression Regulation, Developmental, sense organs, MESH : Vestibular Nuclei, MESH: Potassium Channels, Voltage-Gated
Abstract: International audience; The effect of the lack of vestibular input on the membrane properties of central vestibular neurons was studied by using a strain of transgenic, vestibular-deficient mutant KCNE1(-/-) mice where the hair cells of the inner ear degenerate just after birth. Despite the absence of sensory vestibular input, their central vestibular pathways are intact. Juvenile and adult homozygous mutant have a normal resting posture, but show a constant head bobbing behaviour and display the shaker/waltzer phenotype characterized by rapid bilateral circling during locomotion. In juvenile mice, the KCNE1 mutation was associated with a strong decrease in the expression of the calcium-binding proteins calbindin, calretinin and parvalbumin within the medial vestibular nucleus (MVN) and important modifications of the membrane properties of MVN neurons. In adult mice, however, there was almost no difference between the membrane properties of MVN neurons of homozygous and control or heterozygous mutant mice, which have normal inner ear hair cells and show no behavioural symptoms. The expression levels of calbindin and calretinin were lower in adult homozygous mutant animals, but the amount of calcium-binding proteins expressed in the MVN was much greater than in juvenile mice. These data demonstrate that suppression of sensory vestibular inputs during a 'sensitive period' around birth can generate the circling/waltzing behaviour, but that this behaviour is not due to persistent abnormalities of the membrane properties of central vestibular neurons. Altogether, maturation of the membrane properties of central vestibular neurons is delayed, but not impaired by the absence of sensory vestibular information.
Published: 2007
Full Text: View/download PDF

46. Immune modulation and microchimerism after unmodified versus leukoreduced allogeneic red blood cell transfusion in cancer patients: results of a randomized study

Author: Dominique Tramalloni, Philippe Saas, N. Oubouzar, Christophe Ferrand, Eric Robinet, Pierre Tiberghien, Valérie Lapierre, Anne Auperin, Philippe Lasser, Bertrand Debaene, Institut Gustave Roussy ( IGR ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( PCVP / CARDIO ), Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ) -Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Laboratoire de biologie moléculaire, EFS, Plateforme de Biomonitoring, Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ), Institut Gustave Roussy (IGR), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( EA 3920) (PCVP / CARDIO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté]), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), Marqueurs pronostiques et facteurs de régulations des pathologies cardiaques et vasculaires - UFC ( UR 3920) (PCVP / CARDIO), and Saas, Philippe
Subjects: Male, Blood transfusion, Erythrocytes, medicine.medical_treatment, MESH : Cytokines, MESH : Leukocytes, MESH : Aged, 030204 cardiovascular system & hematology, Blood cell, Blood Transfusion, Autologous, 0302 clinical medicine, MESH: Blood Transfusion, Autologous, Neoplasms, Leukocytes, Immunology and Allergy, Medicine, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, MESH: Neoplasms, MESH : Female, MESH: Aged, MESH: Cytokines, MESH: Middle Aged, MESH: Erythrocytes, MESH : Immune Tolerance, Interleukin, Microchimerism, Forkhead Transcription Factors, hemic and immune systems, Hematology, MESH: Follow-Up Studies, Middle Aged, MESH : Adult, MESH : Survival Rate, 3. Good health, Survival Rate, MESH : Erythrocyte Transfusion, MESH : Forkhead Transcription Factors, MESH : Phenotype, medicine.anatomical_structure, Phenotype, 030220 oncology & carcinogenesis, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Erythrocyte Transfusion, circulatory and respiratory physiology, Adult, MESH: Immune Tolerance, [SDV.IMM] Life Sciences [q-bio]/Immunology, MESH: Survival Rate, MESH : Male, Immunology, MESH: Phenotype, Peripheral blood mononuclear cell, Chimerism, MESH: Leukocytes, 03 medical and health sciences, Immune system, MESH: Forkhead Transcription Factors, Immune Tolerance, Humans, MESH : Middle Aged, Aged, MESH : Blood Transfusion, Autologous, MESH: Humans, business.industry, MESH : Humans, Cancer, MESH: Adult, MESH : Follow-Up Studies, medicine.disease, MESH: Chimerism, MESH : Neoplasms, MESH: Male, Red blood cell, MESH: Erythrocyte Transfusion, MESH : Chimerism, business, MESH: Female, Follow-Up Studies, MESH : Erythrocytes
Abstract: International audience; BACKGROUND: Transfusion of red blood cells (RBCs) has been associated with immunomodulatory effects. Persistence of donor cells in the recipient may be contributive. STUDY DESIGN AND METHODS: A randomized single-center trial was conducted to compare microchimerism and immune responses in 35 patients undergoing cancer surgery and transfused perioperatively with either unmodified RBCs (UN-RBCs, n = 18) or leukoreduced RBCs (LR-RBCs, n = 17). Biologic parameters included microchimerism assessment peripheral blood mononuclear cell (PBMNC) phenotyping, cytokine production by stimulated PBMNCs, FoxP3 gene expression, and T-cell repertoire (TCR) analysis. RESULTS: Microchimerism was documented in 8 of 18 patients after UN-RBC transfusion while absent after LR-RBC transfusion (0/17; p = 0.001). After UN-RBC transfusion, microchimerism was associated with increased interleukin (IL)-10 production (p = 0.02), reduced TCR alteration (p = 0.04), and reduced CD56+ cell counts (p = 0.02) when compared to recipients without evidence for microchimerism. FoxP3 gene expression did not differ significantly between both treatment groups nor with the presence or absence of microchimerism in the UN-RBC group. Finally, after an initial early decrease after surgery and transfusion, IL-12 production increased and more significantly so after UN-RBC transfusion versus LR-RBC transfusion (p = 0.05). CONCLUSION: UN-RBC-induced microchimerism is associated with specific immunomodulatory effects in cancer patients who received transfusions during surgery.
Published: 2007
Full Text: View/download PDF

47. Expression, localization and functions in acrosome reaction and sperm motility of Ca(V)3.1 and Ca(V)3.2 channels in sperm cells: an evaluation from Ca(V)3.1 and Ca(V)3.2 deficient mice.: Cav3.1/3.2 channel functions in sperm physiology

Author: Chien-Chang Chen, Sylvie Boisseau, Jessica Escoffier, Hee-Sup Shin, Séverine Stamboulian, Kevin P. Campbell, Daesoo Kim, Michel De Waard, Catherine Serres, Christophe Arnoult, Canaux calciques , fonctions et pathologies, Université Joseph Fourier - Grenoble 1 (UJF)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Histologie-Embryologie, Biologie de la Reproduction (CECOS Paris Cochin), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Department of Physiology and Biophysics, Howard Hughes Medical Institute (HHMI)-University of Iowa [Iowa City], National CRI Center for Calcium and Learning, Korea Institute of Science and Technology, Inserm, Région Rhône-Alpes, CEA, Collaboration, Université Joseph Fourier - Grenoble 1 ( UJF ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'Histologie-Embryologie, Biologie de la Reproduction ( CECOS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP], and University of Iowa [Iowa City]-Howard Hugues Medical Institute
Subjects: Male, Time Factors, Litter Size, Physiology, Clinical Biochemistry, Acrosome reaction, MESH : Genotype, MESH: Litter Size, MESH: Mice, Knockout, Membrane Potentials, MESH: Genotype, Calcium Channels, T-Type, Mice, MESH : Calcium Signaling, MESH : Membrane Potentials, MESH : Female, MESH: Animals, Zona pellucida, MESH: Acrosome Reaction, Sperm motility, Cells, Cultured, Calcium signaling, Mice, Knockout, 0303 health sciences, Voltage-dependent calcium channel, 030302 biochemistry & molecular biology, MESH: Spermatozoa, MESH: Sperm Motility, Spermatozoa, Cell biology, MESH : Phenotype, medicine.anatomical_structure, Phenotype, Female, MESH : Transfection, MESH : Time Factors, MESH: Cells, Cultured, MESH : Calcium Channels, T-Type, medicine.medical_specialty, Genotype, MESH : Male, acrosome reaction, MESH : Mice, Inbred C57BL, spermatogenic cell, Biology, Transfection, MESH: Phenotype, MESH: Calcium Signaling, 03 medical and health sciences, Calcium imaging, MESH: Calcium Channels, T-Type, MESH: Mice, Inbred C57BL, Internal medicine, MESH : Mice, MESH : Cells, Cultured, medicine, MESH : Spermatozoa, Animals, sperm motility, MESH: Membrane Potentials, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Calcium Signaling, [ SDV.BBM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology, MESH: Mice, 030304 developmental biology, MESH : Acrosome Reaction, MESH: Transfection, MESH: Time Factors, T-type calcium channel, Cell Biology, Sperm, MESH: Male, Mice, Inbred C57BL, MESH : Sperm Motility, Calcium channels, Cav3.2, Endocrinology, MESH : Potassium, MESH: Potassium, Potassium, MESH : Mice, Knockout, MESH : Animals, MESH : Litter Size, MESH: Female, Cav3.1
Abstract: International audience; In spermatozoa, voltage-dependent calcium channels (VDCC) have been involved in different cellular functions like acrosome reaction (AR) and sperm motility. Multiple types of VDCC are present and their relative contribution is still a matter of debate. Based mostly on pharmacological studies, low-voltage-activated calcium channels (LVA-CC), responsible of the inward current in spermatocytes, were described as essential for AR in sperm. The development of Ca(V)3.1 or Ca(V)3.2 null mice provided the opportunity to evaluate the involvement of such LVA-CC in AR and sperm motility, independently of pharmacological tools. The inward current was fully abolished in spermatogenic cells from Ca(V)3.2 deficient mice. This current is thus only due to Ca(V)3.2 channels. We showed that Ca(V)3.2 channels were maintained in sperm by Western-blot and immunohistochemistry experiments. Calcium imaging experiments revealed that calcium influx in response to KCl was reduced in Ca(V)3.2 null sperm in comparison to control cells, demonstrating that Ca(V)3.2 channels were functional. On the other hand, no difference was noticed in calcium signaling induced by zona pellucida. Moreover, neither biochemical nor functional experiments, suggested the presence of Ca(V)3.1 channels in sperm. Despite the Ca(V)3.2 channels contribution in KCl-induced calcium influx, the reproduction parameters remained intact in Ca(V)3.2 deficient mice. These data demonstrate that in sperm, besides Ca(V)3.2 channels, other types of VDCC are activated during the voltage-dependent calcium influx of AR, these channels likely belonging to high-voltage activated Ca(2+) channels family. The conclusion is that voltage-dependent calcium influx during AR is due to the opening of redundant families of calcium channels.
Published: 2007
Full Text: View/download PDF

48. Differentiation in vivo of cardiac committed human embryonic stem cells in postmyocardial infarcted rats. : Human ES cells in postmyocardial infarction

Author: Julia Leschik, Valérie Bellamy, Philippe Menasché, André Tomescot, Michel Pucéat, Michel Desnos, Emmanuel Messas, Michal Amit, Patrick Bruneval, Albert Hagège, Gilbert Dubois, Joseph Itskovitz, Therapie Cellulaire en Pathologie Cardio-Vasculaire ( UMR_S 633 ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Ecole de chirurgie, Assistance publique - Hôpitaux de Paris (AP-HP), Institut des cellules souches pour le traitement et l'étude des maladies monogéniques ( I-STEM ), Université d'Évry-Val-d'Essonne ( UEVE ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de cardiologie [CHU HEGP], Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Immunopathologie humaine, Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service d'anatomo-pathologie [CHU HEGP], Technion - Israel Institute of Technology [Haifa], Service de chirurgie cardiaque et vasculaire [CHU HEGP], AFM, ANR, fondation leducq, and Pr P Menasché HEGP
Subjects: Cellular differentiation, Myocardial Infarction, heart failure, 030204 cardiovascular system & hematology, 0302 clinical medicine, MESH : Myocardium, MESH : Female, Cells, Cultured, 0303 health sciences, MESH : Rats, Cell Differentiation, Heart, [ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, 3. Good health, Endothelial stem cell, MESH : Phenotype, P19 cell, Phenotype, Molecular Medicine, Female, Stem cell, MESH : Cell Differentiation, Adult stem cell, KOSR, Transplantation, Heterologous, MESH : Regeneration, Biology, MESH : Rats, Wistar, Andrology, 03 medical and health sciences, MESH : Heart, MESH : Cells, Cultured, MESH : Embryonic Stem Cells, Animals, Humans, Regeneration, Rats, Wistar, Embryonic Stem Cells, 030304 developmental biology, Myocardium, MESH : Humans, Cell Biology, MESH : Transplantation, Heterologous, Embryonic stem cell, Rats, Transplantation, stem cell, Immunology, MESH : Animals, MESH : Myocardial Infarction, Developmental Biology
Abstract: Human embryonic stem (HES) cells can give rise to cardiomyocytes in vitro. However, whether undifferentiated HES cells also feature a myocardial regenerative capacity after in vivo engraftment has not been established yet. We compared two HES cell lines (HUES-1 and I6) that were specified toward a cardiac lineage by exposure to bone morphogenetic protein-2 (BMP2) and SU5402, a fibroblast growth factor receptor inhibitor. Real-time polymerase chain reaction (PCR) revealed that the cardiogenic inductive factor turned on expression of mesodermal and cardiac genes (Tbx6, Isl1, FoxH1, Nkx2.5, Mef2c, and α-actin). Thirty immunosuppressed rats underwent coronary artery ligation and, 2 weeks later, were randomized and received in-scar injections of either culture medium (controls) or BMP2 (±SU5402)-treated HES cells. After 2 months, human cells were detected by anti-human lamin immunostaining, and their cardiomyocytic differentiation was evidenced by their expression of cardiac markers by reverse transcription-PCR and immunofluorescence using an anti-β myosin antibody. No teratoma was observed in hearts or any other organ of the body. The ability of cardiac-specified HES cells to differentiate along the cardiomyogenic pathway following transplantation into infarcted myocardium raises the hope that these cells might become effective candidates for myocardial regeneration. Disclosure of potential conflicts of interest is found at the end of this article.
Published: 2007
Full Text: View/download PDF

49. Is 2,3,5-pyrroletricarboxylic acid in hair a better risk indicator for melanoma than traditional epidemiologic measures for skin phenotype?

Author: Rosso , Stefano, Zanetti , Roberto, Sánchez , Maria José, Nieto , Adoración, Miranda , Ana, Mercier , Mariette, Loria , Dora, Østerlind , Anne, Greinert , Rüdiger, Chirlaque , Maria-Dolores, Fabbrocini , Gabriella, Barbera , Cesare, Sancho-Garnier , Hélène, Lauria , Carmela, Balzi , Daniela, Zoccola , Marina, Renseigné , Non, Registo Oncológico Regional-Sul, Instituto Português de Oncologia de Francisco Gentil, Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC ( CEF2P / CARCINO ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Université Bourgogne Franche-Comté ( UBFC ) -Université de Franche-Comté ( UFC ), Laboratoire Pierre Süe ( LPS ), Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ), Interactions et dynamique des environnements de surface ( IDES ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut national des sciences de l'Univers ( INSU - CNRS ) -Centre National de la Recherche Scientifique ( CNRS ), Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (EA 3181) (CEF2P / CARCINO), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Laboratoire Pierre Süe (LPS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Interactions et dynamique des environnements de surface (IDES), Université Paris-Sud - Paris 11 (UP11)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), and Carcinogénèse épithéliale : facteurs prédictifs et pronostiques - UFC (UR 3181) (CEF2P / CARCINO)
Subjects: Male, Skin Neoplasms, Epidemiology, MESH : Aged, Gastroenterology, MESH: Spectroscopy, Near-Infrared, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 0302 clinical medicine, MESH: Melanins, Risk Factors, MESH: Risk Factors, Eye color, Medicine, Melanoma, MESH: Aged, 0303 health sciences, Spectroscopy, Near-Infrared, MESH: Middle Aged, Confounding, MESH : Pyrroles, MESH : Hair, MESH : Melanins, Middle Aged, MESH : Adult, MESH: Case-Control Studies, MESH : Risk Factors, 3. Good health, MESH : Phenotype, Phenotype, 030220 oncology & carcinogenesis, MESH: Pyrroles, MESH: Hair, Adult, medicine.medical_specialty, MESH : Case-Control Studies, MESH: Melanoma, MESH: Bayes Theorem, MESH : Male, MESH : Melanoma, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Phenotype, 03 medical and health sciences, MESH : Bayes Theorem, Internal medicine, Humans, Pyrroles, MESH : Middle Aged, Risk factor, 030304 developmental biology, Aged, Melanins, MESH: Humans, business.industry, MESH: Skin Neoplasms, MESH : Skin Neoplasms, MESH : Humans, Bayes Theorem, MESH: Adult, Odds ratio, medicine.disease, Confidence interval, Epidemiologic Measurements, MESH: Male, Surgery, Case-Control Studies, MESH : Spectroscopy, Near-Infrared, business, Hair
Abstract: International audience; This study aims to assess type of melanin as a risk indicator for skin tumors, in a sample of melanoma cases and controls within a larger multicenter study (Helios 2), held in Europe and South America in 2001-2002. In each case and control, the melanin content in hair was assessed by three methods: 1) the amount of 2,3,5-pyrroletricarboxylic acid (PTCA); 2) the absorbance ratio with ultraviolet spectroscopy; and 3) the spectra of near-infrared spectroscopy. Statistical analysis was performed in a Bayesian setting, defining priors for confounders and effect modifiers from the larger study data set. Subjects with values of PTCA of less than 85 ng/mg carried an increased risk (26 vs. seven discordant pairs: odds ratio = 4.4, 95% confidence interval: 1.52, 14.54), adjusted by hair color, eye color, and number of nevi (n = > or =40). The absorbance ratio showed a weaker and nonsignificant odds ratio of 1.5. After correction by misclassification, near-infrared spectroscopy was associated with an odds ratio of 2.3 (95% confidence interval: 1.36, 4.22). The amount of PTCA is thus a strong and independent risk indicator for melanoma. Incorporating PTCA determination into epidemiologic studies is therefore recommended.
Published: 2007
Full Text: View/download PDF

50. [Environmental factors for asthma severity and allergy: results from the EGEA study]

Author: Siroux, Valérie, Oryszczyn, Marie-Pierre, Varraso, Raphaëlle, Le Moual, Nicole, Bousquet, Jean, Charpin, Denis, Gormand, Frédéric, Kennedy, Susan, Maccario, Jean, Pison, Christophe, Rage, Estelle, Scheinmann, Pierre, Vervloet, Daniel, Pin, Isabelle, Kauffmann, Francine, Groupe de Recherche Sur Le Cancer du Poumon : Bases Moléculaires de la Progression Tumorale, Dépistage et Thérapie Génique, Institut Albert Bonniot-Institut National de la Santé et de la Recherche Médicale (INSERM), Recherche en épidémiologie et biostatistique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Immunopathologie de l'Inflammation, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pneumologie-allergologie, Assistance Publique - Hôpitaux de Marseille (APHM), Service de pneumologie [Centre Hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), School of Occupational & Environmental Hygiene, University of British Columbia (UBC), Département de médecine aiguë spécialisée, CHU Grenoble-Hôpital Michallon, Service de Pneumologie Allergologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de Pneumologie-Allergologie [Hôpital de la Timone - APHM], Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille (APHM)-Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Convention INSERM-MSD, réseau INSERM de recherche clinique (489012) et de santé publique (493009), Ministère de la santé, Ministère de l'environnement, Direction de la Recherche Clinique du CHU de Grenoble et COMARES, EGEA, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Albert Bonniot-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Paris-Sud - Paris 11 ( UP11 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Université Montpellier 1 ( UM1 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance Publique - Hôpitaux de Marseille ( APHM ), Centre Hospitalier Lyon Sud [CHU - HCL] ( CHLS ), Hospices Civils de Lyon ( HCL ) -Hospices Civils de Lyon ( HCL ), University of British Columbia ( UBC ), CHU Necker - Enfants Malades [AP-HP]-Assistance publique - Hôpitaux de Paris (AP-HP), and Université de la Méditerranée - Aix-Marseille 2-Assistance Publique - Hôpitaux de Marseille ( APHM ) -Hôpital Sainte-Marguerite [CHU - APHM] ( Hôpitaux Sud )
Subjects: MESH: Premenstrual Syndrome, MESH: Asthma, MESH: Menopause, allergie, MESH : Hypersensitivity, Immediate, MESH : Child, MESH: Risk Factors, MESH: Child, MESH : Female, MESH: Epidemiologic Studies, MESH: Immunoglobulin E, MESH : Menopause, MESH : Menarche, [ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH : Adult, MESH : Eosinophils, MESH : Risk Factors, MESH: Case-Control Studies, MESH : Environment, Environnement, MESH : Smoking, MESH : Phenotype, MESH: Menarche, MESH: Hypersensitivity, Immediate, MESH: Contraceptives, Oral, MESH : Case-Control Studies, MESH: Smoking, MESH: Hypersensitivity, MESH : Male, asthme sévère, MESH : Bronchial Hyperreactivity, MESH : Asthma, MESH: Phenotype, MESH : Epidemiologic Studies, MESH : Immunoglobulin E, MESH: Body Mass Index, MESH: Eosinophils, MESH : Premenstrual Syndrome, MESH : France, MESH: Environment, MESH: Age Factors, MESH : Hypersensitivity, MESH: Humans, MESH : Humans, MESH: Biological Markers, MESH: Bronchial Hyperreactivity, MESH: Adult, MESH: Male, respiratory tract diseases, asthme, MESH : Biological Markers, MESH : Contraceptives, Oral, MESH: France, MESH : Body Mass Index, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH : Age Factors, MESH: Female
Abstract: International audience; INTRODUCTION: EGEA (Epidemiological study on the genetics and environment of asthma, bronchial hyperresponsiveness and atopy), a case control and family study including 2048 individuals, was initiated to look for environmental and genetic risk factors for asthma. A synthesis of the results obtained since 2002 on phenotypic and environmental aspects of asthma severity and allergy are presented in this article. METHODS AND RESULTS: The results support a role for hormonal factors in asthma severity and in various allergic markers of asthma. A greater body mass index was related to a more severe asthma in women with early menarche. Associations between markers of allergy (eosinophils, IgE and atopy) and hormonal dependent events in women (premenstrual asthma, menopause and oral contraceptive use) have been found. In asthmatics, exposure to agents known to be associated with occupational asthma, active and passive smoking were associated with an increased clinical asthma severity score. The study underlines the protective role of country living and exposure to pets in early life on allergy markers in adulthood, supporting the hygiene hypothesis. CONCLUSIONS: New hypothesis will be tested in the near future from the second stage of this survey.
Published: 2007

Catalog

Books, media, physical & digital resources

See catalog results

Searchworks

Select search scope, currently: Articles Catalog books, media & more in Jio Institute collections Articles journal articles & other e-resources

Search

Search Constraints

Refine your results

Search Limiters

Topic

Publication Year Range

Language

Journal

Database

Publisher

60 results on '"MESH : Phenotype"'

Search Results

Catalog

Select search scope, currently: Articles

Catalog

books, media & more in Jio Institute collections

Articles

journal articles & other e-resources