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155 results on '"Croissance cellulaire, réparation et régénération tissulaires (CRRET)"'

1. Variability in proteoglycan biosynthetic genes reveals new facets of heparan sulfates diversity. A systematic review and analysis

Author: Mohand Ouidir Ouidja, Denis S.F. Biard, Sandrine Chantepie, Xavier Laffray, Gael Le Douaron, Minh-Bao Huynh, Nicolas Rebergue, Auriane Maïza, Karla Rubio, Oscar González-Velasco, Guillermo Barreto, Javier De Las Rivas, Dulce Papy-Garcia, Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie François JACOB (JACOB), 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), Max Planck Institute for Heart and Lung Research (MPI-HLR), Max-Planck-Gesellschaft, Universidad de Salamanca, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), and Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)
Subjects: carbohydrates (lipids), [SDV]Life Sciences [q-bio]
Abstract: Proteoglycans are complex macromolecules formed of glycosaminoglycan chains covalently linked to core proteins through a linker tetrasaccharide common to heparan sulfate proteoglycans (HSPG) and chondroitin sulfate proteoglycans (CSPG). Biosynthesis of a single proteoglycan requires the expression of dozens of genes, which together create the large structural and functional diversity reflected by the numerous diseases or syndromes associated to their genetic variability. Among proteoglycans, HSPG are the most structurally and functionally complex. To decrease this complexity, we retrieved and linked information on pathogenic variants, polymorphism, expression, and literature databases for 50 genes involved in the biosynthesis of HSPG core proteins, heparan sulfate (HS) chains, and their linker tetrasaccharide. This resulted in a new gene organization and biosynthetic pathway representation in which the phenotypic continuum of disorders as linkeropathies and other pathologies could be predictable. Moreover, ubiquitous NDST1, GLCE, HS2ST1, and HS6ST1 appeared to generate ubiquitous heparan sulfate (HS) sequences essential for normal development and homeostasis, whereas the tissue restricted NDST2-4, HS6ST2-3, and HS3ST1-6 appeared to generate specialized HS sequences mainly involved in responsiveness to stimuli. Supported by data on genetic polymorphism and clinical variants, we afford a new vision of HSPG involvement in homeostasis, disease, vulnerability to disease, and behavioral disorders.
Published: 2022

2. Matrix therapy combined with mesenchymal stem cells-based approach in the context of brain ischemia

Author: Renoult, Charlène, Khelif, Yacine, Toutain, Jérôme, Quittet, Marie-Sophie, Gal, Rozenn Le, Brunaud, Carole, Laffray, Xavier, Papy-Garcia, Dulcé, Barritault, Denis, Touzani, Omar, Chiappini, Franck, Bernaudin, Myriam, Imagerie et Stratégies Thérapeutiques pour les Cancers et Tissus cérébraux (ISTCT), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Gly-CRRET, FST Université Paris Est Créteil, OTR3 Sarl, OTR3, Centre Hépato-Biliaire [Hôpital Paul Brousse] (CHB), Hôpital Paul Brousse-Assistance Publique - Hôpitaux de Paris, and Couteau, Florence
Subjects: [SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio]
Abstract: CERVOXY; International audience
Published: 2022

3. Cathodic Activation of Titania-Fly Ash Cenospheres for Efficient Electrochemical Hydrogen Production: A Proposed Solution to Treat Fly Ash Waste

Author: Tariq Altalhi, Amine Mezni, Mohamed M. Ibrahim, Moamen S. Refat, Adil A. Gobouri, Ayham M. Safklou, Adel M. Mousli, Mohamed S. Attia, Purna K. Boruah, Manash R. Das, Jacek Ryl, Rabah Boukherroub, Mohammed A. Amin, Taif University (TU), Partenaires INRAE, Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Academy of Scientific and Innovative Research [Ghaziabad, India] (AcSIR), Faculty of Electrical and Control Engineering [GUT Gdańsk] (EIA), Gdańsk University of Technology (GUT), Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520 (IEMN), Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-JUNIA (JUNIA), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), NanoBioInterfaces - IEMN (NBI - IEMN), Université catholique de Lille (UCL)-Université catholique de Lille (UCL)-Centrale Lille-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Université Polytechnique Hauts-de-France (UPHF)-JUNIA (JUNIA), and The authors extend their appreciation to the Deputy for Research & Innovation,Minister of Education in Saudi Arabia for Funding this research work through the project number125-441-1
Subjects: fly ash, titanium dioxide, hybrid nanocomposites, solvothermal process, hydrogen production, [SPI]Engineering Sciences [physics], Physical and Theoretical Chemistry, Catalysis
Abstract: Fly ash (FA) is a waste product generated in huge amounts by coal-fired electric and steam-generating plants. As a result, the use of FA alone or in conjunction with other materials is an intriguing study topic worth exploring. Herein, we used FA waste in conjunction with titanium oxide (TiO2) to create (FA-TiO2) nanocomposites. For the first time, a cathodic polarization pre-treatment regime was applied to such nanocomposites to efficiently produce hydrogen from an alkaline solution. The FA-TiO2 hybrid nanocomposites were prepared by a straightforward solvothermal approach in which the FA raw material was mixed with titanium precursor in dimethyl sulfoxide (DMSO) and refluxed during a given time. The obtained FA-TiO2 hybrid nanocomposites were fully characterized using various tools and displayed a cenosphere-like shape. The synthesized materials were tested as electrocatalysts for the hydrogen evolution reaction (HER) in 0.1 M KOH solution in the dark, employing various electrochemical techniques. The as-prepared (unactivated) FA-TiO2 exhibited a considerable HER electrocatalytic activity, with an onset potential (EHER) value of −144 mV vs. RHE, a Tafel slope (−bc) value of 124 mV dec−1 and an exchange current density (jo) of ~0.07 mA cm−2. The FA-TiO2′s HER catalytic performance was significantly enhanced upon cathodic activation (24 h of chronoamperometry measurements performed at a high cathodic potential of −1.0 V vs. RHE). The cathodically activated FA-TiO2 recorded HER electrochemical kinetic parameters of EHER = −28 mV, −bc = 115 mV dec−1, jo = 0.65 mA cm−2, and an overpotential η10 = 125 mV to yield a current density of 10 mA cm−2. Such parameters were comparable to those measured here for the commercial Pt/C under the same experimental conditions (EHER = −10 mV, −bc = 113 mV dec−1, jo = 0.88 mA cm−2, η10 = 110 mV), as well as to the most active electrocatalysts for H2 generation from aqueous alkaline electrolytes.
Published: 2022

4. 3-O-sulfated heparan sulfate interactors target synaptic adhesion molecules from neonatal mouse brain and inhibit neural activity and synaptogenesis in vitro

Author: Nazha Sidahmed-Adrar, Olivier Stettler, Damien Habert, T.H. van Kuppevelt, Patrick P. Michel, Walid Redouane, Magda Hamza, José Courty, Mohand Ouidir Ouidja, Auriane Maïza, Carine Dalle, Sandrine Chantepie, Gilles Carpentier, Dulce Papy-Garcia, Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Radboud University Medical Center [Nijmegen], Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Gestionnaire, Hal Sorbonne Université
Subjects: Nervous system, Neurogenesis, [SDV]Life Sciences [q-bio], Synaptogenesis, lcsh:Medicine, Peptide, Hippocampus, Interactome, Article, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, medicine, Animals, Receptor, lcsh:Science, Cells, Cultured, 030304 developmental biology, Neurons, chemistry.chemical_classification, 0303 health sciences, Multidisciplinary, integumentary system, Cell adhesion molecule, lcsh:R, Glutamate receptor, Development of the nervous system, Heparan sulfate, Synaptic development, 3. Good health, Cell biology, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10], chemistry, Synapses, lcsh:Q, Heparitin Sulfate, Sulfotransferases, Heparan Sulfate Proteoglycans, 030217 neurology & neurosurgery, Neuroscience
Abstract: Heparan sulfate (HS) chains, covalently linked to heparan sulfate proteoglycans (HSPG), promote synaptic development and functions by connecting various synaptic adhesion proteins (AP). HS binding to AP could vary according to modifications of HS chains by different sulfotransferases. 3-O-sulfotransferases (Hs3sts) produce rare 3-O-sulfated HSs (3S-HSs), of poorly known functions in the nervous system. Here, we showed that a peptide known to block herpes simplex virus by interfering with 3S-HSs in vitro and in vivo (i.e. G2 peptide), specifically inhibited neural activity, reduced evoked glutamate release, and impaired synaptic assembly in hippocampal cell cultures. A role for 3S-HSs in promoting synaptic assembly and neural activity is consistent with the synaptic interactome of G2 peptide, and with the detection of Hs3sts and their products in synapses of cultured neurons and in synaptosomes prepared from developing brains. Our study suggests that 3S-HSs acting as receptors for herpesviruses might be important regulators of neuronal and synaptic development in vertebrates.
Published: 2020

5. Altered fibrin clot structure contributes to thrombosis risk in severe COVID-19

Author: Martin Zacharias, Florian Kurth, Anna Birnhuber, Benjamin Seeliger, Wolfgang M. Kuebler, Fabian Schramm, Gregor Gorkiewicz, Markus C. Brack, Grazyna Kwapiszewska, Leif E. Sander, Liliana Schäfer, Norbert Weissmann, Stefan Hippenstiel, Ralph T. Schermuly, Oleg Pak, Astrid-Solveig Schultz, Klaus T. Preissner, Martin Witzenrath, Malgorzata Wygrecka, Julius J. Schmidt, Guillermo Barreto, Philipp Markart, Tobias Welte, Laura Michalick, Sascha David, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Justus-Liebig-Universität Gießen = Justus Liebig University (JLU), Ludwig Boltzmann Institute for Lung Vascular Research [Graz], Hannover Medical School [Hannover] (MHH), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Medical University Graz, University hospital of Zurich [Zurich], Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), and Goethe-Universität Frankfurt am Main
Subjects: 0303 health sciences, Factor XII, medicine.medical_specialty, biology, Coronavirus disease 2019 (COVID-19), business.industry, medicine.medical_treatment, Kaolin clotting time, [SDV]Life Sciences [q-bio], Thrombolysis, 030204 cardiovascular system & hematology, medicine.disease, Thrombosis, Fibrin, Virus, 3. Good health, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Internal medicine, medicine, biology.protein, Thrombus, business, 030304 developmental biology
Abstract: The high incidence of thrombotic events suggests a possible role of the contact system pathway in COVID-19 pathology. Here, we demonstrate altered levels of factor XII (FXII) and its activation products in two independent cohorts of critically ill COVID-19 patients in comparison to patients suffering from severe acute respiratory distress syndrome due to influenza virus (ARDS-influenza). Compatible with this data, we report rapid consumption of FXII in COVID-19, but not in ARDS-influenza, plasma. Interestingly, the kaolin clotting time was not prolonged in COVID-19 as compared to ARDS-influenza. Using confocal and electron microscopy, we show that increased FXII activation rate, in conjunction with elevated fibrinogen levels, triggers formation of fibrinolysis-resistant, compact clots with thin fibers and small pores in COVID-19. Accordingly, we observed clot lysis in 30% of COVID-19 patients and 84% of ARDS-influenza subjects. Analysis of lung tissue sections revealed wide-spread extra- and intra-vascular compact fibrin deposits in COVID-19. Together, our results indicate that elevated fibrinogen levels and increased FXII activation rate promote thrombosis and thrombolysis resistance via enhanced thrombus formation and stability in COVID-19.
Published: 2021

6. Sex-specific differences in plasma levels of FXII, HK, and FXIIa-C1-esterase inhibitor complexes in community-acquired pneumonia

Author: Guillermo Barreto, Wolfgang M. Kuebler, Jens-Christian Wolff, Kristin Ehrlich, Oleg Pak, Philipp Markart, Norbert Weissmann, Jochen Wilhelm, Liliana Schaefer, Gregor Bein, Malgorzata Wygrecka, Fabian Schramm, Heike Weisser, Werner Seeger, Justus-Liebig-Universität Gießen = Justus Liebig University (JLU), Philipps Universität Marburg = Philipps University of Marburg, Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Goethe-Universität Frankfurt am Main, Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], and Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Pulmonary and Respiratory Medicine, Physiology, High-molecular-weight kininogen, [SDV]Life Sciences [q-bio], Inflammation, Coagulation Factor XII, 030204 cardiovascular system & hematology, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Community-acquired pneumonia, Immunity, Physiology (medical), medicine, Humans, Serum Albumin, Aged, 030304 developmental biology, 0303 health sciences, Factor XII, Estradiol, Kininogens, business.industry, Pneumonia, Cell Biology, medicine.disease, 3. Good health, Community-Acquired Infections, Coagulation, Immunology, Female, medicine.symptom, business, Complement C1 Inhibitor Protein
Abstract: International audience; Sex-dependent differences in immunity and coagulation play an active role in the outcome of community-acquired pneumonia (CAP). Contact phase proteins act at the crossroads between inflammation and coagulation thus representing a point of convergence in host defense against infection. Here, we measured the levels of factor XII (FXII), FXIIa-C1 esterase inhibitor (C1INH) complexes, and high-molecular-weight kininogen (HK) in plasma of patients with CAP and correlated them to clinical disease severity. Levels of FXIIa-C1INH/albumin ratio were elevated, irrespective of sex, in plasma of patients with CAP ( n = 139) as compared with age-matched donors ( n = 58). No simultaneous decrease in FXII levels, indicating its consumption, was observed. Stratification by sex revealed augmented FXII levels in plasma of women with CAP as compared with sex-matched donors yet no apparent differences in men. This sex-specific effect was, however, attributable to lower FXII levels in female donors relative to men donors. Plasma estradiol levels mirrored those for FXII. Levels of HK/albumin ratio were decreased in CAP plasma as compared with donors, however, after stratification by sex, this difference was only observed in women and was related to higher HK/albumin values in female donors as opposed to male donors. Finally, strong negative correlation between plasma levels of HK/albumin ratio and CAP severity, as assessed by CRB65 score, in males and females was observed. Our study identifies sex-dependent differences in plasma levels of the contact phase proteins in elderly subjects that may contribute to specific clinical outcomes in CAP between men and women.
Published: 2021

7. Process Development and Manufacturing: CHARACTERIZATION OF THE ACOUSTIC CONTRAST FACTOR: A NEW APPROACH FOR A LABEL-FREE SEPARATION OF THE STROMAL VASCULAR FRACTION

Author: Sugier, H.R., Bellebon, L., Larghero, J., Peltzer, J., Aider, Jean-Luc, Martinaud, C., Aenitis Technologies, INSERM U1197, Physique et mécanique des milieux hétérogenes (UMR 7636) (PMMH), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Université Paris sciences et lettres (PSL), Centre de Transfusion Sanguine des Armées (CTSA), and Service de Santé des Armées
Subjects: Cancer Research, Transplantation, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Oncology, Immunology, Immunology and Allergy, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Cell Biology, Genetics (clinical), [PHYS.MECA.ACOU]Physics [physics]/Mechanics [physics]/Acoustics [physics.class-ph]
Published: 2022

8. Lymphoid-specific helicase in epigenetics, DNA repair and cancer

Author: Shuang Liu, Yuyi Li, Guillermo Barreto, Yamei Li, Yongguang Tao, Xiangyu Chen, Karla Rubio, Bi Deng, Chao Mao, Qinwei Tang, Desheng Xiao, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Central South University [Changsha], Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Max Planck Institute for Heart and Lung Research (MPI-HLR), and Max-Planck-Gesellschaft
Subjects: Cancer Research, DNA End-Joining Repair, DNA Repair, DNA repair, [SDV]Life Sciences [q-bio], Review Article, Biology, medicine.disease_cause, Epigenesis, Genetic, 03 medical and health sciences, 0302 clinical medicine, parasitic diseases, medicine, Nucleosome, Animals, Humans, Epigenetics, Homologous Recombination, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, DNA Helicases, Chromatin Assembly and Disassembly, 3. Good health, Chromatin, Cell biology, Histone, Oncology, 030220 oncology & carcinogenesis, DNA methylation, biology.protein, Carcinogenesis, Homologous recombination
Abstract: Lymphoid-specific helicase (LSH) is a member of the SNF2 helicase family of chromatin-remodelling proteins. Dysfunctions or mutations in LSH causes an autosomal recessive disease known as immunodeficiency-centromeric instability-facial anomaly (ICF) syndrome. Interestingly, LSH participates in various aspects of epigenetic regulation, including nucleosome remodelling, DNA methylation, histone modifications and heterochromatin formation. Further, LSH plays a crucial role during DNA-damage repair, specifically during double-strand break (DSB) repair, since murine LSH was shown to be essential for non-homologous end joining (NHEJ) and homologous recombination (HR). Accordingly, overexpression of LSH drives tumorigenesis and malignancy. On the other hand, LSH homologs stabilise the genome. Thus, LSH might be implemented as a biomarker for various cancer types and potential target molecule to develop therapeutic strategies against them. In this review, we focus on the role of LSH in orchestrating chromatin rearrangements, such as DNA methylation and histone modifications, as well as in DNA-damage repair. Changes in chromatin structure may facilitate gene expression signatures that cause malignant transformation. We summarise recent findings of LSH in cancers and raise critical open questions for further studies.
Published: 2021

9. Chirurgie de l’arthrose des membres inférieurs chez le sujet âgé

Author: Victor Housset, Charles-Henri Flouzat-Lachaniette, F. Eymard, Claire Bastard, Arnaud Dubory, David Giber, CHRU Brest - Service chirurgie orthopédique et traumatologique (CHU - BREST - Orthopédie ), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Croissance cellulaire, réparation et régénération tissulaires (CRRET), and Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 030203 arthritis & rheumatology, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, [SDV]Life Sciences [q-bio], 030212 general & internal medicine, 3. Good health
Abstract: Resume L’arthrose des membres inferieurs s’accompagne de douleurs et d’une gene fonctionnelle, invalidantes au quotidien. Lorsque le traitement medical est depasse, la mise en place de protheses est le traitement de choix chez le sujet âge. L’objectif de ce travail est de rapporter les specificites liees au patient, aux techniques operatoires et aux implants dans le traitement chirurgical de l’arthrose des membres chez le sujet âge. Les patients âges ayant beneficie d’une pose de prothese totale de hanche ou de genou pour arthrose necessitent souvent plusieurs semaines de recuperation. Ils obtiennent d’excellents resultats a long terme au prix d’une hospitalisation plus longue et de taux de complications post-operatoires et de mortalite plus eleves. L’adaptation de la strategie chirurgicale et le type d’implants utilises doivent etre adaptes aux risques specifiques des sujets âges. La prise en charge doit integrer une cogestion geriatrique avant et apres la chirurgie afin de reduire le taux de complications mineures.
Published: 2019

10. Functional interactions between scaffold proteins, noncoding RNAs, and genome loci induce liquid‐liquid phase separation as organizing principle for 3‐dimensional nuclear architecture: implications in cancer

Author: Karla Rubio, Guillermo Barreto, Stephanie Dobersch, Max Planck Institute for Heart and Lung Research (MPI-HLR), Max-Planck-Gesellschaft, Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Kazan Federal University (KFU), and University of Giessen and Marburg Lung Center (UGMLC)
Subjects: 0301 basic medicine, Scaffold protein, RNA, Untranslated, Organizing principle, Nucleolus, [SDV]Life Sciences [q-bio], Liquid-Liquid Extraction, Computational biology, Biochemistry, Genome, Nuclear architecture, 03 medical and health sciences, Adenosine Triphosphate, 0302 clinical medicine, Nuclear Matrix-Associated Proteins, Neoplasms, Genetics, Humans, Liquid liquid, Phosphorylation, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Eukaryotic cell, Cell Nucleus, Genome, Human, Chemistry, Cell Membrane, Chromatin, Structure and function, MicroRNAs, 030104 developmental biology, Mutation, Cell Nucleolus, 030217 neurology & neurosurgery, Protein Binding, Signal Transduction, Biotechnology
Abstract: The eukaryotic cell nucleus consists of functionally specialized subcompartments. These nuclear subcompartments are biomolecular aggregates built of proteins, transcripts, and specific genome loci. The structure and function of each nuclear subcompartment are defined by the composition and dynamic interaction between these 3 components. The spatio-temporal localization of biochemical reactions into membraneless nuclear subcompartments can be achieved through liquid-liquid phase separation. Based on this organizing principle, nuclear subcompartments are droplet-like structures that adopt spherical shapes, flow, and fuse like liquids or gels. In the present review, we bring into the spotlight seminal works elucidating the functional interactions between scaffold proteins, noncoding RNAs, and genomic loci, thereby inducing liquid-liquid phase separation as an organizing principle for 3-dimensional nuclear architecture. We also discuss the implications in different cancer types as well as the potential use of this knowledge to develop novel therapeutic strategies against cancer.-Rubio, K., Dobersch, S., Barreto, G. Functional interactions between scaffold proteins, noncoding RNAs, and genome loci induce liquid-liquid phase separation as organizing principle for 3-dimensional nuclear architecture: implications in cancer.
Published: 2019

11. Positioning of nucleosomes containing γ-H2AX precedes active DNA demethylation and transcription initiation

Author: Karla Rubio, Saverio Bellusci, C.-M. Chao, Thomas Braun, Malgorzata Wygrecka, Julio Cordero, M. B. Huynh, K. Preissner, Rafael Castillo-Negrete, Andreas Guenther, Hector A. Cabrera-Fuentes, Guillermo Barreto, Indrabahadur Singh, Stephanie Dobersch, Dulce Papy-Garcia, Stefan Guenther, Johannes Graumann, Gergana Dobreva, Jürgen Bernhagen, Aditi Mehta, P. Bruabach, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL), Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Max Planck Institute for Heart and Lung Research (MPI-HLR), Max-Planck-Gesellschaft, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Medical Faculty [Mannheim], Ludwig-Maximilians-Universität München (LMU), Hannover Medical School [Hannover] (MHH), Justus-Liebig-Universität Gießen = Justus Liebig University (JLU), National Heart Centre Singapore (NHCS), Tecnológico de Monterrey (ITESM), Duke-National University of Singapore Graduate Medical School, Institute for Stroke and Dementia Research (ISD), Klinikum der Universität [München]-Ludwig Maximilian University [Munich] (LMU), Munich Cluster for systems neurology [Munich] (SyNergy), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU), and Wenzhou Medical University [Wenzhou, China] (WMU)
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], General Physics and Astronomy, Ataxia Telangiectasia Mutated Proteins, Histones, chemistry.chemical_compound, Mice, Phosphoserine, 0302 clinical medicine, Transcription (biology), Histone post-translational modifications, Phosphorylation, Transcription Initiation, Genetic, Histone variants, 0303 health sciences, Multidisciplinary, biology, Chemistry, 030302 biochemistry & molecular biology, Hmg protein, Chromatin, 3. Good health, Cell biology, Nucleosomes, DNA Demethylation, Histone, DNA methylation, Epigenetics, RNA Polymerase II, Transcription Initiation Site, Transcriptional Activation, DNA repair, Science, Chromatin structure, General Biochemistry, Genetics and Molecular Biology, Article, Transforming Growth Factor beta1, 03 medical and health sciences, Nucleosome, Animals, Humans, 030304 developmental biology, HMGA2 Protein, General Chemistry, Idiopathic Pulmonary Fibrosis, 030104 developmental biology, DNA demethylation, HEK293 Cells, biology.protein, 030217 neurology & neurosurgery, DNA
Abstract: In addition to nucleosomes, chromatin contains non-histone chromatin-associated proteins, of which the high-mobility group proteins are the most abundant. Chromatin-mediated regulation of transcription involves DNA methylation and histone modifications. However, the order of events and the precise function of high-mobility group proteins during transcription initiation remain unclear. Here we show that high-mobility group AT-hook 2 protein (HMGA2) induces DNA nicks at the transcription start site, which are required by the histone chaperone FACT complex to incorporate nucleosomes containing the histone variant H2A.X. Further, phosphorylation of H2A.X at S139 (γ-H2AX) is required for repair-mediated DNA demethylation and transcription activation. The relevance of these findings is demonstrated within the context of TGFB1 signaling and idiopathic pulmonary fibrosis, suggesting therapies against this lethal disease. Our data support the concept that chromatin opening during transcriptional initiation involves intermediates with DNA breaks that subsequently require DNA repair mechanisms to ensure genome integrity., The order of DNA methylation and histone modifications during transcription remained unclear. Here the authors show that HMGA2 induces DNA nicks at TGFB1-responsive genes, promoting nucleosome incorporation containing γ-H2AX, which is required for repair-mediated DNA demethylation and transcription.
Published: 2021

12. Role of adipose tissues in osteoarthritis

Author: Florent Eymard, Xavier Houard, Natalia Zapata-Linares, Francis Berenbaum, Centre de Recherche Saint-Antoine (CR Saint-Antoine), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de rhumatologie [CHU Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and Gestionnaire, Hal Sorbonne Université
Subjects: 0301 basic medicine, Male, Knee Joint, [SDV]Life Sciences [q-bio], Subcutaneous Fat, Adipose tissue, Context (language use), Osteoarthritis, Bioinformatics, Bone and Bones, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, Adipokines, Endocrine system, Medicine, Humans, Obesity, Pathological, 030203 arthritis & rheumatology, Infrapatellar fat pad, business.industry, Mesenchymal stem cell, Mesenchymal Stem Cells, Osteoarthritis, Knee, medicine.disease, Magnetic Resonance Imaging, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, Adipose Tissue, Disease Progression, Female, Bone marrow, business
Abstract: International audience; Purpose of review: Epidemiologic studies reveal that the link between obesity and osteoarthritis cannot be uniquely explained by overweight-associated mechanical overload. For this reason, much attention focuses on the endocrine activity of adipose tissues. In addition to the systemic role of visceral and subcutaneous adipose tissues, many arguments highlight the involvement of local adipose tissues in osteoarthritis.Recent findings: Alteration in MRI signal intensity of the infrapatellar fat pad may predict both accelerated knee osteoarthritis and joint replacement. In this context, recent studies show that mesenchymal stromal cells could play a pivotal role in the pathological remodelling of intra-articular adipose tissues (IAATs) in osteoarthritis. In parallel, recent findings underline bone marrow adipose tissue as a major player in the control of the bone microenvironment, suggesting its possible role in osteoarthritis.Summary: The recent description of adipose tissues of various phenotypes within an osteoarthritic joint allows us to evoke their direct involvement in the initiation and progression of the osteoarthritic process. We can expect in the near future the discovery of novel molecules targeting these tissues.
Published: 2021

13. N6L-functionalized nanoparticles for targeted and inhibited pancreatic cancer cells

Author: Damien Habert, Ilaria Cascone, Tina Modjinou, Sena Hamadi, José Courty, Sabrina Belbekhouche, Mélissande Cossutta, Institut de Chimie et des Matériaux Paris-Est (ICMPE), Institut de Chimie du CNRS (INC)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Croissance cellulaire, réparation et régénération tissulaires (CRRET), and Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Chemistry, Nanoparticle, Context (language use), 02 engineering and technology, 010402 general chemistry, 021001 nanoscience & nanotechnology, 01 natural sciences, Nanocapsules, 0104 chemical sciences, 3. Good health, Allylamine, chemistry.chemical_compound, Colloid and Surface Chemistry, Colloidal gold, Cancer cell, Drug delivery, Zeta potential, Biophysics, [CHIM]Chemical Sciences, 0210 nano-technology, ComputingMilieux_MISCELLANEOUS
Abstract: Pancreatic cancer is a growing cause of concern, leading to an increasing number of deaths worldwide. Most of the antitumor drugs for pancreatic cancer are given by systemic administration. However, even if this is at therapeutic doses, its tends to lead to severe side-effects because of nonspecific uptake by healthy tissues. In this context, we aim to develop an innovative drug delivery approach for the treatment of pancreatic cancer based on tailor-made nanomaterials with presenting controlled size, chemistry and stiffness. In this study, we have designed tailor-made N6L-nanomaterials, via the combination of both a templating method and a self-assembly process onto colloidal gold nanoparticles (diameters 20 nm and 60 nm) using a core template. The removal of the core leads to hollow particles, also called capsules. We judiciously functionalised the outer layer of the nanomaterial with N6L, which corresponds to a synthetic agent that is non-toxic to normal mammalian cells, targets surface nucleolin and induces tumour cell death by apoptosis. Our data demonstrated, via quartz crystal microbalance measurement, the possibility of directly using N6L in a self-assembly process through electrostatic interactions. In addition, as shown by measuring zeta potential values, we showed that electrostatic interactions between the protonated amine groups of poly (allylamine) macromolecules (+40 mV), the sulphate groups of dextran derivatives (−20 mV) and the protonated amine groups of N6L (+20 mV) are the driving attraction force during multilayer fabrication onto colloidal gold. Transmission electron microscopy was used to confirm that the gold nanoparticles were coated and the nanocapsules were formed. Finally, we successfully showed that these N6L-based nanostructures target cancer cells and inhibited, in a dose dependent manner, cell survival in pancreatic cancer model. This result clearly highlights the potential antitumor activity of the developed nanostructures.
Published: 2020

14. Loss of LRP1 promotes acquisition of contractile-myofibroblast phenotype and release of active TGF-β1 from ECM stores

Author: Jochen Wilhelm, Karla Rubio, Clemens Ruppert, Guillermo Barreto, Grazyna Kwapiszewska, Philipp Markart, Lukasz Wujak, Liliana Schaefer, Malgorzata Wygrecka, Argen Mamazhakypov, Anna Birnhuber, Jennifer Schnieder, University of Giessen and Marburg Lung Center [Gießen, Germany] (UGMLC), Ludwig Boltzmann Institute for Lung Vascular Research [Graz], Philipps University of Marburg, Max Planck Institute for Heart and Lung Research (MPI-HLR), Max-Planck-Gesellschaft, Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Goethe-University Frankfurt am Main, Philipps Universität Marburg = Philipps University of Marburg, and Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Population, Integrin, Low-density lipoprotein receptor-related protein 1, Mice, Transgenic, Fos-Related Antigen-2, Periostin, Contractility, Cell Line, Extracellular matrix, Transforming Growth Factor beta1, 03 medical and health sciences, Mice, 0302 clinical medicine, Fibrosis, medicine, Animals, Humans, RNA, Small Interfering, education, Myofibroblasts, Molecular Biology, education.field_of_study, Phenotypic switch, biology, Chemistry, medicine.disease, LRP1, Actins, Cell biology, 030104 developmental biology, Phenotype, 030220 oncology & carcinogenesis, biology.protein, Myofibroblast, Low Density Lipoprotein Receptor-Related Protein-1, Transforming growth factor, Signal Transduction
Abstract: International audience; In healing tissue, fibroblasts differentiate to α-smooth muscle actin (SMA)-expressing contractile-myofibroblasts, which pull the wound edges together ensuring proper tissue repair. Uncontrolled expansion of the myofibroblast population may, however, lead to excessive tissue scarring and finally to organ dysfunction. Here, we demonstrate that the loss of low-density lipoprotein receptor-related protein (LRP) 1 overactivates the JNK1/2-c-Jun-Fra-2 signaling pathway leading to the induction of α-SMA and periostin expression in human lung fibroblasts (hLF). These changes are accompanied by increased contractility of the cells and the integrin- and protease-dependent release of active transforming growth factor (TGF)-β1 from the extracellular matrix (ECM) stores. Liberation of active TGF-β1 from the ECM further enhances α-SMA and periostin expression thus accelerating the phenotypic switch of hLF. Global gene expression profiling of LRP1-depleted hLF revealed that the loss of LRP1 affects cytoskeleton reorganization, cell-ECM contacts, and ECM production. In line with these findings, fibrotic changes in the skin and lung of Fra-2 transgenic mice were associated with LRP1 depletion and c-Jun overexpression. Altogether, our results suggest that dysregulation of LRP1 expression in fibroblasts in healing tissue may lead to the unrestrained expansion of contractile myofibroblasts and thereby to fibrosis development. Further studies identifying molecules, which regulate LRP1 expression, may provide new therapeutic options for largely untreatable human fibrotic diseases.
Published: 2020

15. Non-coding RNAs and nuclear architecture during epithelial-mesenchymal transition in lung cancer and idiopathic pulmonary fibrosis

Author: Guillermo Barreto, Karla Rubio, Rafael Castillo-Negrete, Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Kazan Federal University (KFU), Max Planck Institute for Heart and Lung Research (MPI-HLR), Max-Planck-Gesellschaft, and University of Giessen and Marburg Lung Center [Gießen, Germany] (UGMLC)
Subjects: 0301 basic medicine, Epithelial-Mesenchymal Transition, Lung Neoplasms, RNA, Untranslated, [SDV]Life Sciences [q-bio], Cell, Biology, Fibroblast growth factor, 03 medical and health sciences, Idiopathic pulmonary fibrosis, 0302 clinical medicine, Fibrosis, Epidermal growth factor, medicine, Humans, Epithelial–mesenchymal transition, Transcription factor, Lung, Wnt signaling pathway, Cell Biology, medicine.disease, Idiopathic Pulmonary Fibrosis, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cancer research
Abstract: International audience; Lung cancer (LC) is the leading cause of cancer-related deaths worldwide. On the other hand, idiopathic pulmonary fibrosis (IPF) is the most common interstitial lung disease showing a prevalence of 20 new cases per 100,000 persons per year. Despite differences in cellular origin and pathological phenotypes, LC and IPF are lung diseases that share common features, including hyperproliferation of specific cell types in the lung, involvement of epithelial-mesenchymal transition (EMT) and enhanced activity of signaling pathways, such as tissue growth factor (TGFB), epidermal growth factor (EGF), fibroblast growth factor (FGF), wingless secreted glycoprotein (WNT) signaling, among others. EMT is a process during which epithelial cells lose their cell polarity and cell-cell adhesion, and acquire migratory and invasive properties to become mesenchymal cells. EMT involves numerous morphological hallmarks of hyperproliferative diseases, like cell plasticity, resistance to apoptosis, dedifferentiation and proliferation, thereby playing a central role during organ fibrosis and cancer progression. EMT was considered as an "all-or-none" process. In contrast to these outdated dichotomist interpretations, recent reports suggest that EMT occurs gradually involving different epithelial cell intermediate states with mesenchyme-like characteristics. These cell intermediate states of EMT differ from each other in their cell plasticity, invasiveness and metastatic potential, which in turn are induced by signals from their microenvironment. EMT is regulated by several transcription factors (TFs), which are members of prominent families of master regulators of transcription. In addition, there is increasing evidence for the important contribution of noncoding RNAs (ncRNAs) to EMT. In our review we highlight articles dissecting the function of different ncRNAs subtypes and nuclear architecture in cell intermediate states of EMT, as well as their involvement in LC and IPF.
Published: 2020

16. Metastasis-Associated Protein 2 Represses NF-κB to Reduce Lung Tumor Growth and Inflammation

Author: Nefertiti El-Nikhely, Soni Savai Pullamsetti, Friedrich Grimminger, Ulf R. Rapp, Indrabahadur Singh, Astrid Wietelmann, Andreas Weigert, Annika Karger, Guillermo Barreto, Reinhard Dammann, Poonam Sarode, Werner Seeger, Ludger Fink, Rajkumar Savai, Thorsten Stiewe, Max Planck Institute for Heart and Lung Research (MPI-HLR), Max-Planck-Gesellschaft, Institut für Biochemie II [Goethe-University Frankfurt am Main] (IBC2), Goethe-University Frankfurt am Main, German Center for Lung Research, Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), and Justus-Liebig-Universität Gießen = Justus Liebig University (JLU)
Subjects: 0301 basic medicine, Cancer Research, Epithelial-Mesenchymal Transition, Lung Neoplasms, [SDV]Life Sciences [q-bio], Mice, Transgenic, Biology, Histone Deacetylases, Metastasis, 03 medical and health sciences, 0302 clinical medicine, Downregulation and upregulation, Cell Line, Tumor, medicine, Tumor Microenvironment, Animals, Humans, MTA2, Lung cancer, ComputingMilieux_MISCELLANEOUS, Inflammation, NF-kappa B, medicine.disease, Mi-2/NuRD complex, Primary tumor, 3. Good health, I-kappa B Kinase, Gene Expression Regulation, Neoplastic, Mice, Inbred C57BL, Repressor Proteins, 030104 developmental biology, HEK293 Cells, Oncology, 030220 oncology & carcinogenesis, Cancer research, Trans-Activators, Signal transduction, Corepressor, Signal Transduction
Abstract: Although NF-κB is known to play a pivotal role in lung cancer, contributing to tumor growth, microenvironmental changes, and metastasis, the epigenetic regulation of NF-κB in tumor context is largely unknown. Here we report that the IKK2/NF-κB signaling pathway modulates metastasis-associated protein 2 (MTA2), a component of the nucleosome remodeling and deacetylase complex (NuRD). In triple transgenic mice, downregulation of IKK2 (Sftpc-cRaf-IKK2DN) in cRaf-induced tumors in alveolar epithelial type II cells restricted tumor formation, whereas activation of IKK2 (Sftpc-cRaf-IKK2CA) supported tumor growth; both effects were accompanied by altered expression of MTA2. Further studies employing genetic inhibition of MTA2 suggested that in primary tumor growth, independent of IKK2, MTA2/NuRD corepressor complex negatively regulates NF-κB signaling and tumor growth, whereas later dissociation of MTA2/NuRD complex from the promoter of NF-κB target genes and IKK2-dependent positive regulation of MTA2 leads to activation of NF-κB signaling, epithelial–mesenchymal transition, and lung tumor metastasis. These findings reveal a previously unrecognized biphasic role of MTA2 in IKK2/NF-κB-driven primary-to-metastatic lung tumor progression. Addressing the interaction between MTA2 and NF-κB would provide potential targets for intervention of tumor growth and metastasis. Significance: These findings strongly suggest a prominent role of MTA2 in primary tumor growth, lung metastasis, and NF-κB signaling modulatory functions.
Published: 2020

17. Rilpivirine in HIV-1-positive women initiating pregnancy

Author: Frange, Pierre, Tubiana, Roland, Sibiude, Jeanne, Canestri, Ana, Arvieux, Cédric, Brunet-Cartier, Cécile, Cotte, Laurent, Reynes, Jacques, Mandelbrot, Laurent, Warszawski, Josiane, Le Chenadec, Jérôme, Crenn-Hebert, Catherine, Floch-Tudal, Corinne, Mazy, Fabienne, Joras, Marine, Meier, Françoise, Mortier, Emmanuel, Briquet, Catherine, Ichou, Houria, Marty, Laurence, Jabbarian, Hélène, Ceccaldi, Pierre-François, Villemant, Agnès, Zarouk, Virginie, Lefort, Agnès, Ben Salah, Mariam, Hittinger, Gilles, Chamouilli, Jean-Marc, Burle, Christian, Lafeuillade, Alain, Philip, Gisèle, Lambry, Véronique, Medus, Marie, Bachelard, Germaine, Malet, Martine, Dendale-Nguyen, Joëlle, Guimard, Thomas, Guimard, Karine, Brossier, Jean-Pierre, Perre, Philippe, Esnault, Jean-Luc, Aubry, Olivier, Leautez-Nainville, Sophie, Bonnenfant, Valerie, Laine, Laeticia, Martha, Sandrine-Anne, Maurel, Elise, Francoise, Michel, Barat, Muriel, Murger, Patricia, Rouha, Mahfoud, Lévy, Marc, Lumbroso, Philippe, Checoury, Alain, Sahadatu, Osseni, Perfezou, Pascale, Blondin, Gilles, Ansart, Séverine, De Saint Martin, Luc, Le Moine, Philippe, Duthé, Jean-Charles, Daniel, Corinne, Calvez, Christian, Boutaric, Emmanuelle, Rohan, Jennifer, Bauville, Estelle, Dupre, Christelle, Lotton, Pascal, Ouamara-digue, Enora, Poinsignon, Yves, Goussef, Marie, Grelier, Anne, Mousset, Gaetane, Cudeville, Corinne, Niault, Mathilde, Belzic, Isabelle, Moreau, Philippe, Le Coz, Marie-Françoise, Vaillant, Odile Luycx, Guerin-Duplessy, Anne, Mouton-Rioux, Virginie, De Morel, Philippe, Vitrat, Virginie, Tardif, Didier, Gaillat, Jacques, Vanderbergh, Anne, Braig, Suzanne, Clavere, Gaelle, Dehlinger-Paul, Marion, Mohamed, Khaled, Echard, Marie, Camus, Michel, Mulard, Catherine, Fontelonga, Marie-Agnès, Heller-Roussin, Brigitte, Winter, Cécile, Challier, Marion, Debruyne, Elise, Marcou, Valerie, Firtion, Ghislaine, Pannier, Emmanuelle, Costa, Myriam, Launay, Odile, Salmon-Ceron, Dominique, Belkacem, Touria, Bajawi, Youcef, Aubret, Valérie Raynal, Rivaux, Danièle, Elaoun, Neila, Allal, Lahcene, Djoubou, Sandrine, Rahli, Djamila, Moine, Agnès Bourgeois, Valentin, Morgane, Damond, Florence, Huri, Virginie, Vivier, Valérie, Yahia, Fatma Ait, Garrait, Valérie, Hau, Isabelle, Touboul, Claudine, Ratsimbazafy, Lanto, Boiron, Emilie, Elharrar, Brigitte, Labaune, Jean-Marc, Rudigoz, Rene-Charles, Brochier, Corinne, Galvan, Valérie, Ogoudjobi, Stanislas, Elleau, Christophe, Runel-Belliard, Camille, Pistone, Thierry, Fleury, Hervé, Horovitz, Jacques, Sandler, Boris, Roux, Denis, Ragnaud, Jean-Marie, Chabanier, Pierre, Brun, Jean-Luc, Delveaux, Sandrine, Muanza, Blandine, Diallo, Mama Doufari, Lamaury, Isabelle, Sow, Marie-Thérèse, Samar, Ketty, Carpentier, Bénédicte, Osman, Zafer, Dienga, Etienne, Seaume, Hervé, Ducrocq, Sarah, Bailly-Salin, Philippe, Da Silva, Christelle Dusart, Fayolas, Isabelle, Abbal, Julie, Simon-Toulza, Caroline, Truillet, Véronique, Bogner, Noëlle, Chiabrando, Julie, Armand, Evelyne, Cayla, Claudine, Chacé, Anne, Matheron, Isabelle, Richier, Laurent, Miantezila, Joe, Bry, Sandrine, Couderc, Sophie, Narcy, Catherine, Routier, Corinne, Nassar, Rania, Bouldouyre, Marie-Anne, Zakaria, Ahmed, Dauphin, Hélène, Goissen, Céline, Belloy, Marie, Delassus, Jean-Luc, Favret, Véronique, Nemeth, Céline, Partisani, Marialuisa, Entz-Werlé, Natacha, Langer, Bruno, Uettwiller, Françoise, Durand, Myriam, Partizani, MariaLuisa, Cheneau, Christine, Rey, David, Ebel, Edith, Fischer, Patricia, DAVID, Eric, Vayssière, Christophe, Weil, Michèle, Schmitt, Marie Paule, Nisand, Israël, Genet, Philippe, Brault, Dominique, Allisy, Christine, Gerbe, Juliette, Masse, Virginie, Wifaq, Bouchra, Courdavault, Laurence, Gabor, Petra, Tordjeman, Nathalie, Lebrette, Marie-Gisèle, Selleret, Lise, Samama, Déborah, Bolot, Pascal, Khuong-Josses, Marie-Aude, Amel, Mahdi, Bounan, Stéphane, Nourry, Christelle, Andris, Sabine, Blanche, Stephane, Driessen, Marine, Veber, Florence, Fischer, Alain, Rouzioux, Christine, Avettand-Fenoël, Véronique, Mahlaoui, Nizar, Mourey, Marie-Christine, Granier, Michèle, Devidas, Alain, Donnadieu, Anne-Claire, May, Adrien, Chabrol, Amélie, Chevojon, Pierre, Bellahcene, Chahrazede, Sanchez, Audrey, Malbrunot, Claire, Neizelien, Joelle, Agher, Nouara, Pluchart, Claire, Rouger, Christine, Dommergues, Marc, Bonmarchand, Manuela, Shneider, Luminata, Caby, Fabienne, Calin, Ruxandra-Oana, Blanc, Christine, Lupin, Catherine, Pauchard, Michèle, Yangui, Mohamed Amine, Roca, Didier, Todorova, Darina, Laurent, Juliette, Ferry, A., Deschaud, Martine, Blum, Laurent, Chambrin, Véronique, Labrune, Philippe, Clech, Laure, Raho-Moussa, Mariem, Pauly-Ravelly, Isolde, Jault, Thierry, Bouabdallah, Soufiane, Sanchez, Lydie, Sanchez, Anita, Johnson, Ama, Louchard, Agnès, Allouche, Claude, Pathe, Jean-Paul, Lachassine, Eric, Benoist, Laurence, Jeantils, Vincent, Delannoy, Catherine, Benbara, Amélie, Carbillon, Lionel, Borgne, Anne, Moreau, Laurence, PICARD, Fabienne, Karaoui, Leïla, Elbert, Véronique Lefevre, Balaz, Valérie, Bongain, André, Monpoux, Fabrice, Deville, Anne, Galiba, Eliane, Jabbar, Ahmed, Joutel, Martine, Schmidt, Jean-Luc, Decaux, Nathalie, Cravello, Ludovic, Errichiello, Katia, Hubert, Claire, Dollfus, Catherine, Hervé, François, Tabone, Marie-Dominique, Courcoux, Mary-France, Leverger, Guy, Kayem, Gilles, Schnurgier, Aurélie, Jensen, Aurore, Vaudre, Geneviève, Pinquier, Didier, Gromez, Alexis, Pinto-Cardoso, Gaelle, Faye, Albert, Borie, Constance, Levine, Martine, Matheron, Sophie, Marouts, Erianna Bellaton, Boissinot, Christine, Caseris, Marion, Pommelet, Virginie, Morau, Geneviève, Leveille, Sandrine, Boumediene, Marie Astride, Garion, Dominique, Peretti, Delphine, Fourcade, Corinne, Houllier, Marie, Jrad, Ikram, Bourdic, Katia, Monnier, Sylvie, Chirouze, Catherine, Proust, Aurélie, Catteau, Odile, Gardiennet, Quentin, Reliquet, Véronique, Winer, Norbert, Vaucel, Edouard, Rodallec, Audrey, Garnier-André, Elisabeth, Briandet, Claire, Brouard, Jacques, Goubin, Pascale, Beucher, Gaël, Dina, Julia, Demersay, Arnaud Chalvon, Tassi, Sylvie, Lavarenne, Gaelle, Rajguru, Mandovi, Messaoudi, Fabienne, Carré, Nathalie, Rajguru, Mandavi, Bobrie-Moyrand, Claire, Foucaud, Pierre, Bernard, Louis, Maakroun, Zoha, Bourgault, Olivier, Kebaili, Kamila, Bertrand, Yves, Alixe, Véronique, Boyer, Emeline, Billiemaz, Kareen, Fanget, Cécile, Ronat, Véronique, Lesauder, Catherine, Lavastre, Marie Laure, Moulin, Alice, Turquini, Marie-France, Colombani, Dominique, Belgodere, Danièle, Fialaire, Pascale, Proust, Stéphanie, Rehaiem, Sami, Mesnard, Louis, Werner, Evelyne, Dukiel, Nathalie, Desmergers, Baya, Blanc-Ruffat, Isabelle, Maraux, Barbara, Coursol, Anne, Castaneda, Julie, Etienne, Lise, Vintejoux, Emmanuelle, Lalande, Muriel, Segondy, Michel, Guigue, Nelly, De Gennes, Christiane, Clavel, Cyril, Cazassus, François, Walter, Véronique, Mazingue, Françoise, Hammou, Yamina, Lagree, Marion, Paquiez, Odile, D’angelo, Sophie, Boquet, Laurence, Ajana, Faiza, Hatchuel, Yves, Nahri, Imad, Zebelus, Jenny, Genet, Claire, Ducroix-Roubertou, Sophie, Aubrard, Yves, Constanty, Anne, Weinbreck, Pierre, Piet, Emilie, Jacquier, Françoise, Michaud, Christophe, Safwan, Hassan, Boutet, Arnaud, Grand-Courault, Carole, Autret, Fanny, Habibi, Fakher, Azria, Elie, Abdelhadi, Mohamed, Elenga, Narcisse, Bocket, Laurence, Taillet, Françoise, Palenzuela, Gilles, Khadly, Redouane, Pierronnet, Danielle, Dos-Santos, Emmanuelle, David, Selva, Makhloufi, Djamila, Brunel-Dalmas, Florence, Carbonnel-Delalande, Elisabeth, Chiarello, Pierre, Godinot, Matthieu, Gilbert, Sylvie, Massardier, Jérôme, Gauthier-Moulinier, Hélène, Fernandes, Elisabeth, Ranaivojaona, Sata, Chevry, Coralie, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), 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) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Maladies infectieuses et tropicales [CHU Tenon], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service des maladies infectieuses et réanimation médicale [Rennes] = Infectious Disease and Intensive Care [Rennes], CHU Pontchaillou [Rennes], Centre hospitalier universitaire de Nantes (CHU Nantes), Département de maladies infectieuses, Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques er émergentes (TransVIHMI), Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Hôpital Louis Mourier - AP-HP [Colombes], Chirurgie Gynécologique et Obstétrique (CGO), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'infectiologie [AP-HP Hôpital Louis Mourier, Colombes], Faculté de Médecine Paris-Diderot [Paris], Université Paris Diderot - Paris 7 (UPD7), Service de Médecine Interne [AP-HP, CHU Beaujon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Beaujon [AP-HP], Service de médecine interne, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, Service de pédiatrie, Centre Hospitalier Chalon-sur-Saône William Morey, CH de Lorient, Laboratoire de Traitement de l'Information Medicale (LaTIM), Université européenne de Bretagne - European University of Brittany (UEB)-Université de Brest (UBO)-Télécom Bretagne-Institut Mines-Télécom [Paris] (IMT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Unité d'hémato-oncologie, CHU Toulouse [Toulouse], Pôle Médico-Chirurgical de Pédiatrie et de Génétique Clinique, Néonatologie, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Service de Gynécologie et Obstétrique [Rennes] = Gynaecology [Rennes], CH Bretagne Sud, Centre d'Investigations Biomédicales - Hématologie - Oncologie - Greffes (CIB-HOG), Centre d'Investigations Biomédicales - Hématologie - Oncologie - Greffes-Hopital St Louis, Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Service des Maladies Infectieuses, Centre Hospitalier de la Région d'Annecy (Pringy), University of Warwick [Coventry], Physiopathologie et Pharmacotoxicologie Placentaire Humaine (U1139), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Cochin [AP-HP], Université Paris Descartes - Paris 5 (UPD5), Service de Virologie [CHU Bichat], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Hôpital de la Croix-Rousse [CHU - HCL], Réseau périnatal Aurore, Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), CHU Bordeaux [Bordeaux], pôle gynécologie-obstétrique et médecine foetale, Laboratoire Rhéologie et Procédés (LRP), Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), Université Grenoble Alpes (UGA), Fédération des Maladies Infectieuses [Bordeaux], CHU de Bordeaux Pellegrin [Bordeaux], Centre de compétences des microangiopathies thrombotiques, department of pathology, university hospital, parakou, CHU Pointe-à-Pitre/Abymes [Guadeloupe], Service des Maladies Infectieuses et Tropicales[Point-à-Pitre], Service de Gynécologie-Obstétrique [Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), CHU Strasbourg, Développement et physiopathologie de l'intestin et du pancréas, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de gynécologie–obstétrique, CHU Strasbourg-Hôpital de Hautepierre [Strasbourg], CHRU Strasbourg, Département d'échographie et de Médecine fœtale, SIHCUS-CMCO, Service de Gynécologie-Obstétrique, CHI Poissy-Saint-Germain, Centre Hospitalier Victor Dupouy, Service d'informatique médicale et biostatistiques [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Hôpital d'Argenteuil, Centre Hospitalier de Saint-Denis [Ile-de-France], Hôpital Delafontaine, Recherche Epidémiologique en Santé Périnatale et Santé des Femmes et des Enfants (UMR_S 953), Université Paris-Sud - Paris 11 (UP11)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de microbilogie & unité d'immunologie, hématologie et rhumatologie pédiatriques, 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), Chaire Médecine expérimentale (A. Fischer), Collège de France (CdF (institution)), Laboratoire de Virologie [CHU Necker], Université Sorbonne Paris Cité (USPC), 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), Médecine néonatale, Centre Hospitalier Sud Francilien, Service de pneumologie [Béclère], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Centre Hospitalier Universitaire de Reims (CHU Reims), Service de Gynécologie-Obstétrique, Maternité, Chirurgie Gynécologique [CHU Pitié-Salpêtrière], Service de médecine interne [CHU Pitié-Salpétrière], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Hôpital Antoine Béclère, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Référence Maladies Héréditaires du Métabolisme Hépatique [Hôpital Antoine Béclère - APHP (CRMR), Service de rhumatologie [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Service de gynécologie-obstétrique [Hôpital Jean Verdier], Université Paris 13 (UP13)-Hôpital Jean Verdier [AP-HP], Service de Gynécologie-Obstétrique-Reproduction, Hôpital l'Archet, Service d'Hémato-oncologie Pédiatrique [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Trousseau [APHP], Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Epidémiologie Clinique et Evaluation Economique Appliquées aux Populations Vulnérables (ECEVE (U1123 / UMR_S_1123)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Service des maladies infectieuses et tropicales, Service de pédiatrie générale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Institut Pasteur du Laos, Réseau International des Instituts Pasteur (RIIP), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de Gynécologie Obstétrique, Service de Médecine Interne et Immunologie clinique [AP-HP Hôpital Bicêtre], Hôpital Bicêtre, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), service de maladies infectieuses CHU J Minjoz Besancon, Service des maladies infectieuses et tropicales [CHU Nantes], Physiopathologie des Adaptations Nutritionnelles (PhAN), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Service de virologie [CHU Nantes], Service de Pédiatrie Enfants - Hématologie Oncologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Pédiatrie Médicale [Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Gynécologie-Obstétrique et Médecine de la Reproduction [CHU Caen], Service de Virologie [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Médecine Interne et Maladies Infectieuses [Tours], Service d'hématologie : Immuno-Hématologie pédiatrique et transplantation de moelle osseuse, Hôpital Debrousse, CHU Saint-Etienne, Centre population et développement (CEPED - UMR_D 196), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Médecine Néonatale et Réanimation Pédiatrique, CH René Dubos, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service des Maladies Infectieuses et Tropicales [Hôpital Gustave Dron, Tourcoing], Centre Hospitalier Gustave Dron [Tourcoing], 'Personal Protection Against Vectors' working group (PPAV), PPAV working group, Service des Maladies infectieuses et tropicales [CHU Limoges], CHU Limoges, Equipe de Recherche Médicale Appliquée (ERMA), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), CHU Annecy, Service de Pédiatrie, Centre hospitalier de Saint-Nazaire, EA 3593 Université des Antilles et de la Guyane, Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française]-Centre Hospitalier Andrée Rosemon [Cayenne, Guyane Française], Laboratoire de virologie [CHU Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Maladies Infectieuses et Tropicales [Hôpital de la Croix-Rousse - HCL], Service d'immunologie, Hospices Civils de Lyon (HCL)-Hôpital Edouard Herriot [CHU - HCL], Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Centre Hospitalier de Basse-Terre, Recherches Translationnelles sur le VIH et les maladies infectieuses endémiques et émergentes (TransVIHMI), Université de Rennes (UR), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Collège de France - Chaire Médecine expérimentale (A. Fischer), Laboratoire Chrono-environnement (UMR 6249) (LCE), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), ANRS CO1/CO11, French national, Viral Hepatitis, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), 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), Service des maladies infectieuses et tropicales [CHU Tenon], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de Recherche pour le Développement (IRD)-Université de Yaoundé I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), Hôpital Beaujon [AP-HP], 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 européenne de Bretagne - European University of Brittany (UEB)-Télécom Bretagne-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Mines-Télécom [Paris] (IMT), Hôpital des Enfants, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris-Sud - Paris 11 (UP11), CH Evry-Corbeil-CH Evry-Corbeil, CH Evry-Corbeil, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Hôpital Jean Verdier [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris 13 (UP13), Université Paris Diderot - Paris 7 (UPD7)-AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Laboratoire d'Electrotechnique de Lyon (LEL), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon, Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Université de Limoges (UNILIM)-CHU Limoges, Institut National de la Santé et de la Recherche Médicale (INSERM)-AP-HP Hôpital universitaire Robert-Debré [Paris], Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Université de Montpellier (UM)
Subjects: rilpivirine, viral suppression, hiv, hiv-1, pregnancy, conception, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, virology
Abstract: International audience; BackgroundSafety data about rilpivirine use during pregnancy remain scarce, and rilpivirine plasma concentrations are reduced during second/third trimesters, with a potential risk of viral breakthroughs. Thus, French guidelines recommend switching to rilpivirine-free combinations (RFCs) during pregnancy.ObjectivesTo describe the characteristics of women initiating pregnancy while on rilpivirine and to compare the outcomes for virologically suppressed subjects continuing rilpivirine until delivery versus switching to an RFC.MethodsIn the ANRS-EPF French Perinatal cohort, we included women on rilpivirine at conception in 2010–18. Pregnancy outcomes were compared between patients continuing versus interrupting rilpivirine. In women with documented viral suppression (
Published: 2020

18. Particulate inorganic salts and trace element emissions of a domestic boiler fed with five commercial brands of wood pellets

Author: Hélène Lavanant, Stéphane Marcotte, Nadine Merlet-Machour, Luis Carrasco-Cabrera, Carlos Afonso, Christophe Morin, Florence Medaerts, Clément Castilla, Chimie Organique et Bioorganique : Réactivité et Analyse (COBRA), Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie Organique Fine (IRCOF), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut national des sciences appliquées Rouen Normandie (INSA Rouen Normandie), Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire (INC3M), Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Université Le Havre Normandie (ULH), Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Institut de Chimie du CNRS (INC)-École Nationale Supérieure d'Ingénieurs de Caen (ENSICAEN), Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie Organique Fine (IRCOF), and Institut National des Sciences Appliquées (INSA)-Normandie Université (NU)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Pollution, Health, Toxicology and Mutagenesis, media_common.quotation_subject, Pellets, Air pollution, chemistry.chemical_element, 010501 environmental sciences, Combustion, medicine.disease_cause, 01 natural sciences, 7. Clean energy, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, medicine, Environmental Chemistry, [CHIM]Chemical Sciences, 0105 earth and related environmental sciences, media_common, Air Pollutants, Cadmium, Trace element, General Medicine, Particulates, Wood, Trace Elements, Coal, chemistry, 13. Climate action, Environmental chemistry, Stove, Environmental science, Particulate Matter
Abstract: International audience; Pellet stoves arouse a real interest from consumers because they are perceived as a renewable and carbon neutral energy. However, wood combustion can contribute significantly to air pollution, in particular through the emission of particulate matter (PM). In this article, five brands of wood pellets were burnt under optimal combustion conditions and trace element and inorganic salt emission factors (EFs) in PM were determined. Results show that a significant proportion of metals such as lead, zinc, cadmium, and copper initially present in pellets were emitted into the air during combustion with 20 ± 6%, 31 ± 12%, and 19 ± 6% of the initial content respectively for Zn, Pb, and Cd. The median emission factors for Pb, Cu, Cd, As, Zn, and Ni were respectively 188, 86, 9.3, 8.7, 2177, and 3.5 μg kg−1. The inorganic fraction of the PM emissions was dominated by K+, SO42−, and Cl− with respective EFs of 33, 28.7, and 11.2 mg kg−1. Even taking into account a consumption of 40.1 million tons by 2030 in the EU, the resulting pollution in terms of heavy metal emissions remains minimal in comparison with global emissions in the EU.
Published: 2020

19. The Nucleolin Antagonist N6L Inhibits LINE1 Retrotransposon Activity in Non-Small Cell Lung Carcinoma Cells

Author: Marco A. Tavera-Garcia, Elsa M. Reyes-Reyes, Ilaria Cascone, Isabel Runge, Kenneth S. Ramos, José Courty, Sara Moore, University of Arizona, Croissance cellulaire, réparation et régénération tissulaires (CRRET), and Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Somatic cell, Retrotransposon, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biology, NSCLC, 03 medical and health sciences, 0302 clinical medicine, and Lung cancer, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Lung cancer, 030304 developmental biology, Nucleolin, 0303 health sciences, Gene knockdown, LINE1, medicine.disease, Reverse transcriptase, 3. Good health, Long interspersed nuclear element, Oncology, Cell culture, 030220 oncology & carcinogenesis, Cancer research, Research Paper
Abstract: International audience; Lung cancer is the most common cause of cancer death in the United States. The genome of non-small cell lung cancer (NSCLC), the most frequent lung cancer type, is strongly affected by Long Interspersed Nuclear Element (LINE1) insertions. Active LINE1s are repetitive DNA sequences that can amplify themselves in the genome utilizing a retrotransposition mechanism whereby LINE1 is copied via reverse transcription and inserted at target sites. ORF1p and ORF2p are LINE1 encoded proteins essential for LINE1 retrotransposition. LINE1s are silenced epigenetically in somatic tissues, and their reactivation has been associated with cancer pathogenesis. Here, we present evidence that nucleolin (NCL) regulates expression of LINE1-ORF1p (L1-ORF1p) in NSCLC cells. Genetic knockdown of NCL significantly inhibited expression of L1-ORF1p in various NSCLC cell lines. Treatment with the investigational NCL antagonist N6L ablated L1-ORF1p expression in all cell lines constitutively expressing L1-ORFp. N6L displayed a stronger antiproliferative activity in NSCLC tumor cell lines expressing the highest L1-ORF1p protein levels. Moreover, N6L treatment of nude mice bearing NSCLC tumor xenografts blocked L1-ORF1p expression and effectively inhibited tumor growth. These data indicate that L1-ORF1p expression is regulated by NCL and identify NCL as a novel promising target for pharmacological inhibition of LINE1.
Published: 2020

20. 3-O-sulfated heparan sulfate interactors target synaptic adhesion molecules from neonatal mouse brain and inhibit neural activity and synaptogenesis in vitro

Author: Courty, José, Laboratoire CRRET, EAC/CNRS-7149, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Croissance cellulaire, réparation et régénération tissulaires (CRRET), and Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2020

21. L'incapacité à réguler à la baisse l'expression de miR-154 dans l'épithélium pulmonaire postnatal précoce de la souris supprime l'alvéologénèse, avec des modifications de la signalisation Tgf-β similaires à celles induites par l'exposition à l'hyperoxie

Author: Chao, Cho-Ming, Carraro, Gianni, Rako, Zvonimir, Kolck, Johannes, Sedighi, Jamschid, Zimmermann, Volker, Moiseenko, Alena, Wilhelm, Jochen, Young, Brittany, Chong, Lei, Wu, Jin, Contreras, Adriana, Minoo, Parviz, Barreto, Guillermo, Warburton, David, Bellusci, Saverio, Wenzhou Medical University [Wenzhou, China] (WMU), Justus-Liebig-Universität Gießen = Justus Liebig University (JLU), Cedars-Sinai Medical Center, University of California [Los Angeles] (UCLA), University of California (UC), Max-Planck-Institut, Children’s Hospital Los Angeles [Los Angeles], Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), and Justus-Liebig-Universität Gießen (JLU)
Subjects: [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, AT2, [SDV.BDD.EO]Life Sciences [q-bio]/Development Biology/Embryology and Organogenesis, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], hyperoxia, alveolar simplification, respiratory system, Tgf-ß1, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, miR-154, Caveolin1
Abstract: International audience; Background: Bronchopulmonary dysplasia (BPD) is a lung disease of preterm born infants, characterized by alveolar simplification. MicroRNA (miR) are known to be involved in many biological and pathological processes in the lung. Although a changed expression has been described for several miR in BPD, a causal role remains to be established.Results: Our results showed that the expression level of miR-154 increases during lung development and decreases postnatally. Further, hyperoxia treatment maintains high levels of miR-154 in alveolar type 2 cells (AT2). We hypothesized that the decrease in miR-154 expression in AT2 cells is required for normal alveologenesis. To test this hypothesis, we generated a novel transgenic mouse allowing doxycycline-based miR-154 overexpression. Maintenance of miR-154 expression in the postnatal distal lung epithelium under normoxia conditions is sufficient to reproduce the hypoalveologenesis phenotype triggered by hyperoxia. Using a pull-down assay, we identified Caveolin1 as a key downstream target of miR-154. Caveolin1 protein is downregulated in response to overexpression of miR-154. This is associated with increased phosphorylation of Smad3 and Tgf-ß signaling. We found that AT2 cells overexpressing miR-154 display decreased expression of AT2 markers and increased expression of AT1 markers.Conclusion: Our results suggest that down-regulation of miR-154 in postnatal lung may function as an important physiological switch that permits the induction of the correct alveolar developmental program, while conversely, failure to down-regulate miR-154 suppresses alveolarization, leading to the common clinically observed phenotype of alveolar simplification.
Published: 2020

22. 3-O-sulfated heparan sulfate interactors target synaptic adhesion molecules from neonatal mouse brain and inhibit neural activity and synaptogenesis in vitro

Author: Stettler, Olivier, Croissance cellulaire, réparation et régénération tissulaires (CRRET), and Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS)
Subjects: [SDV]Life Sciences [q-bio], ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2020

23. Inactivation of nuclear histone deacetylases by EP300 disrupts the MiCEE complex in idiopathic pulmonary fibrosis

Author: Rajkumar Savai, Julio Cordero, Peter Braubach, Malgorzata Wygrecka, Soni Savai-Pullamsetti, Saverio Bellusci, Karla Rubio, Lukasz Wujak, Mathias Heikenwalder, Hector A. Cabrera-Fuentes, Aditi Mehta, Thomas Braun, Stephanie Dobersch, Stefan Günther, Cho-Ming Chao, Dulce Papy-Garcia, Andreas Günther, Werner Seeger, Indrabahadur Singh, Klaus T. Preissner, Gergana Dobreva, Guillermo Barreto, Pouya Sarvari, Max Planck Institute for Heart and Lung Research (MPI-HLR), Max-Planck-Gesellschaft, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Heidelberg University, Medical Faculty [Mannheim], Ludwig-Maximilians-Universität München (LMU), Justus-Liebig-Universität Gießen (JLU), National Heart Centre Singapore (NHCS), Kazan Federal University (KFU), Tecnológico de Monterrey (ITESM), Duke-National University of Singapore Graduate Medical School, Wenzhou Medical University [Wenzhou, China] (WMU), Hannover Medical School [Hannover] (MHH), Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Justus-Liebig-Universität Gießen = Justus Liebig University (JLU), and Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)
Subjects: 0301 basic medicine, Male, [SDV]Life Sciences [q-bio], General Physics and Astronomy, Histone Deacetylase 2, Histone Deacetylase 1, 02 engineering and technology, Non-coding RNAs, chemistry.chemical_compound, Idiopathic pulmonary fibrosis, Mice, Histone post-translational modifications, Medicine, lcsh:Science, Lung, Cells, Cultured, Multidisciplinary, respiratory system, 021001 nanoscience & nanotechnology, Chromatin, humanities, 3. Good health, medicine.anatomical_structure, Ribonucleoproteins, 0210 nano-technology, Transcription, Science, Primary Cell Culture, Bleomycin, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, microRNA, Gene silencing, Animals, Humans, Epigenetics, Gene Silencing, EP300, Cell Nucleus, Respiratory tract diseases, business.industry, General Chemistry, Fibroblasts, medicine.disease, Idiopathic Pulmonary Fibrosis, respiratory tract diseases, Disease Models, Animal, MicroRNAs, 030104 developmental biology, chemistry, Cancer research, lcsh:Q, business, E1A-Associated p300 Protein, Ex vivo
Abstract: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and highly lethal lung disease with unknown etiology and poor prognosis. IPF patients die within 2 years after diagnosis mostly due to respiratory failure. Current treatments against IPF aim to ameliorate patient symptoms and to delay disease progression. Unfortunately, therapies targeting the causes of or reverting IPF have not yet been developed. Here we show that reduced levels of miRNA lethal 7d (MIRLET7D) in IPF compromise epigenetic gene silencing mediated by the ribonucleoprotein complex MiCEE. In addition, we find that hyperactive EP300 reduces nuclear HDAC activity and interferes with MiCEE function in IPF. Remarkably, EP300 inhibition reduces fibrotic hallmarks of in vitro (patient-derived primary fibroblast), in vivo (bleomycin mouse model), and ex vivo (precision-cut lung slices, PCLS) IPF models. Our work provides the molecular basis for therapies against IPF using EP300 inhibition., Idiopathic pulmonary fibrosis (IPF) is a lethal disease with insufficient treatment strategies. Here the authors show that reduction of the microRNA MIRLET7D and hyperactivation of EP300 contribute to impaired epigenetic silencing by the MiCEE complex in pulmonary fibroblasts of IPF patients, and demonstrate the benefit of inhibiting EP300 for the treatment of IPF.
Published: 2019

24. SLC10A7 mutations cause a skeletal dysplasia with amelogenesis imperfecta mediated by GAG biosynthesis defects

Author: Dubail, Johanne, Huber, Céline, Chantepie, Sandrine, Sonntag, Stephan, Tüysüz, Beyhan, Mihci, Ercan, Gordon, Christopher T., Steichen-Gersdorf, Elisabeth, Amiel, Jeanne, Nur, Banu, Stolte-Dijkstra, Irene, van Eerde, Albertien M., van Gassen, Koen L., Breugem, Corstiaan C., Stegmann, Alexander, Lekszas, Caroline, Maroofian, Reza, Karimiani, Ehsan Ghayoor, Bruneel, Arnaud, Seta, Nathalie, Munnich, Arnold, Papy-Garcia, Dulce, De La Dure-Molla, Muriel, Cormier-Daire, Valérie, ARD - Amsterdam Reproduction and Development, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Necker - Enfants Malades [AP-HP], Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), PolyGene AG [Rümlang, Switzerland], Department of Pediatric Genetics [Istanbul, Turkey] (Cerrahpasa Medicine School), Istanbul University, Paediatric Genetic Department [Antalya, Turkey], Akdeniz University, Innsbruck Medical University [Austria] (IMU), University Medical Center Groningen [Groningen] (UMCG), University Medical Center [Utrecht], Division of Paediatric Plastic Surgery [Utrecht, The Netherlands], Wilhelmina Children´s Hopsital [Utrecht, The Netherlands], Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Radboud University Medical Center [Nijmegen], Julius-Maximilians-Universität Würzburg [Wurtzbourg, Allemagne] (JMU), Molecular and Clinical Sciences Institute - St George’s [London, UK] (Genetics Research Centre), University of London [London], Next Generation Genetic Clinic [Mashhad, Iran], Razavi Cancer Research Center [Mashhad, Iran] (Razavi Hospital), Imam Reza International University [Mashhad, Iran], CIC Hôpital Bichat, Institut National de la Santé et de la Recherche Médicale (INSERM)-UFR de Médecine-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 des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Sorbonne Université - Faculté de Médecine (SU FM), Sorbonne Université (SU), This work was supported by the European Community’s Seventh Framework Programme (FP7/2007-2013) under grant agreement number 602300 (SYBIL) and the Fondation pour la Recherche Médicale (FRM) funding (DEQ20120323703)., European Project: 602300,EC:FP7:HEALTH,FP7-HEALTH-2013-INNOVATION-1,SYBIL(2013), Gestionnaire, Hal Sorbonne Université, Systems biology for the functional validation of genetic determinants of skeletal diseases - SYBIL - - EC:FP7:HEALTH2013-10-01 - 2018-09-30 - 602300 - VALID, Innsbruck Medical University = Medizinische Universität Innsbruck (IMU), Julius-Maximilians-Universität Würzburg (JMU), 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-UFR de Médecine, MUMC+: DA KG Lab Centraal Lab (9), MUMC+: DA Pat Cytologie (9), RS: GROW - R4 - Reproductive and Perinatal Medicine, Wilhelmina Children’s Hospital, and École Pratique des Hautes Études (EPHE)
Subjects: Electrophoresis, Chemistry(all), Amelogenesis Imperfecta, DISORDERS, PROTEINS, Science, GROWTH-PLATE, [SDV]Life Sciences [q-bio], Organic Anion Transporters, Sodium-Dependent, HEPARAN-SULFATE PROTEOGLYCANS, PHENOTYPES, Physics and Astronomy(all), Osteochondrodysplasias, Article, CALCIUM, Mice, Chlorocebus aethiops, Animals, Humans, Exome, Child, lcsh:Science, Glycoproteins, GLYCOSAMINOGLYCANS, Mice, Knockout, Bone Diseases, Developmental, Symporters, Biochemistry, Genetics and Molecular Biology(all), Body Weight, CHONDROITIN, Infant, GENE, [SDV] Life Sciences [q-bio], Disease Models, Animal, HEK293 Cells, Child, Preschool, COS Cells, Mutation, lcsh:Q, REGULATOR
Abstract: Skeletal dysplasia with multiple dislocations are severe disorders characterized by dislocations of large joints and short stature. The majority of them have been linked to pathogenic variants in genes encoding glycosyltransferases, sulfotransferases or epimerases required for glycosaminoglycan synthesis. Using exome sequencing, we identify homozygous mutations in SLC10A7 in six individuals with skeletal dysplasia with multiple dislocations and amelogenesis imperfecta. SLC10A7 encodes a 10-transmembrane-domain transporter located at the plasma membrane. Functional studies in vitro demonstrate that SLC10A7 mutations reduce SLC10A7 protein expression. We generate a Slc10a7−/− mouse model, which displays shortened long bones, growth plate disorganization and tooth enamel anomalies, recapitulating the human phenotype. Furthermore, we identify decreased heparan sulfate levels in Slc10a7−/− mouse cartilage and patient fibroblasts. Finally, we find an abnormal N-glycoprotein electrophoretic profile in patient blood samples. Together, our findings support the involvement of SLC10A7 in glycosaminoglycan synthesis and specifically in skeletal development., The majority of skeletal dysplasia are caused by pathogenic variants in genes required for glycosaminoglycan (GAG) metabolism. Here, Dubail et al. identify genetic variants in the solute carrier family protein SLC10A7 in families with skeletal dysplasia and amelogenesis imperfecta that disrupt GAG synthesis.
Published: 2018

25. A clinical‐grade acellular matrix for esophageal replacement

Author: Mohamed Jarraya, Niclas Setterblad, Jérôme Larghero, Valérie Vanneaux, Lousineh Arakelian, Camille Flageollet, Sara Shamdani, Patrick Bruneval, Sabrina Kellouche, Laurent Corté, Clémentine Caille, Thomas Domet, Pierre Cattan, Patricia Albanese, Lionel Faivre, Université Paris sciences et lettres (PSL), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Croissance, Réparation et Régénération Tissulaires (CRRET), EAC 7149-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Drexel University, Plate-forme d'imagerie, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Equipe de recherche sur les relations matrice extracellulaire-cellules (ERRMECe), Fédération INSTITUT DES MATÉRIAUX DE CERGY-PONTOISE (I-MAT), Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine-Université de Cergy Pontoise (UCP), Université Paris-Seine-Université Paris-Seine, Service d'Immunopathologie [Hôpital Saint-Louis, Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Cell Therapy Unit, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité de Thérapie Cellulaire, Hopital St Louis, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité)
Subjects: Pathology, medicine.medical_specialty, Swine, 0206 medical engineering, Biomedical Engineering, Medicine (miscellaneous), 02 engineering and technology, Matrix (biology), Biomaterials, Extracellular matrix, 03 medical and health sciences, chemistry.chemical_compound, Esophagus, Tissue engineering, Materials Testing, medicine, Animals, [CHIM]Chemical Sciences, Sodium dodecyl sulfate, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, [PHYS]Physics [physics], 0303 health sciences, Decellularization, Tissue Engineering, Tissue Scaffolds, Chemistry, Stomach, Mesenchymal stem cell, Mesenchymal Stem Cells, 020601 biomedical engineering, Extracellular Matrix, medicine.anatomical_structure
Abstract: In pathologies of the esophagus such as esophageal atresia, cancers, and caustic injuries, methods for full thickness esophageal replacement require the sacrifice of healthy intra-abdominal organs such as the stomach and the colon and are associated with high morbidity, mortality, and poor functional results. To overcome these problems, tissue engineering methods are developed to create a substitute with scaffolds and cells. The aim of this study was to develop a simple and safe decellularization process in order to obtain a clinical grade esophageal extracellular matrix. Following the decontamination step, porcine esophagi were decellularized in a bioreactor with sodium dodecyl sulfate and ethylenediaminetetraacetic acid for 3 days and were rinsed with deionized water. DNA was eliminated by a 3-hr DNase treatment. To remove any residual detergent, the matrix was then incubated with an absorbing resin. The resulting porcine esophageal matrix was characterized by the assessment of the efficiency of the decellularization process (DNA quantification), evaluation of sterility and absence of cytotoxicity, and its composition and biomechanical properties, as well as the possibility to be reseeded with mesenchymal stem cells. Complete decellularization with the preservation of the general structure, composition, and biomechanical properties of the native esophageal matrix was obtained. Sterility was maintained throughout the process, and the matrix showed no cytotoxicity. The resulting matrix met clinical grade criteria and was successfully reseeded with mesenchymal stem cells..
Published: 2019

26. Fetal bovine serum impacts the observed N‐glycosylation defects in TMEM165 KO HEK cells

Author: Climer, Leslie, Morelle, Willy, De Bettignies, Geoffroy, Krzewinski Recchi, Marie-Ange, Lupashin, Vladimir, Medina-Cano, Daniel, Ucuncu, Ekin, Nguyen, Lam Son, Nicouleau, Michael, Lipecka, Joanna, Bizot, Jean-Charles, Thiel, Christian, Lefort, Nathalie, Faivre-Sarrailh, Catherine, Colleaux, Laurence, Guerrera, Ida Chiara, Cantagrel, Vincent, Lebredonchel, Elodie, Garat, Anne, Legrand, Dominique, Decool, Valérie, Klein, André, Ouzzine, Mohamed, Gasnier, Bruno, Potelle, Sven, Groux‐Degroote, Sophie, Cogez, Virginie, Noel, Maxence, Portier, Lucie, Solórzano, Carlos, Dall'Olio, Fabio, Steenackers, Agata, Mortuaire, Marlène, Gonzalez‐Pisfil, Mariano, Henry, Mélanie, Heliot, Laurent, Harduin-Lepers, Anne, Berthe, Audrey, Zaffino, Marie, Muller, claire, Houdou, Marine, Schulz, Céline, Bost, Frédéric, De Fay, Elia, Mazerbourg, Sabine, Flament, Stéphane, Mouajjah, Dounia, Ashikov, Angel, Abu Bakar, Nurulamin, Wen, Xiao-Yan, Niemeijer, Marco, Rodrigues Pinto Osorio, Glentino, Brand-Arzamendi, Koroboshka, Hasadsri, Linda, Hansikova, Hana, Raymond, Kimiyo, Ondruskova, Nina, Simon, Marleen, Pfundt, Rolph, Timal, Sharita, Beumers, Roel, Smeets, Roel, Kersten, Marjan, Huijben, Karin, Linders, Peter, van den Bogaart, Geert, van Hijum, Sacha, Rodenburg, Richard, van den Heuvel, Lambertus, Van Spronsen, Francjan, Honzik, Tomas, van Scherpenzeel, Monique, Lefeber, Dirk, Mirjam, Wamelink, Han, Brunner, Helen, Mundy, Helen, Michelakakis, Peter, van Hasselt, Jiddeke, van de Kamp, Diego, Martinelli, Lars, Morkrid, Katja, Brocke Holmefjord, Jozef, Hertecant, Majid, Alfadhel, Kevin, Carpenter, Johann, te Water Naude, Delos, Maxime, Hellec, Charles, Fifre, Alexandre, Carpentier, Mathieu, Papy-Garcia, Dulce, Allain, Fabrice, Denys, Agnés, Gilormini, Pierre André, Lion, Cédric, Vicogne, Dorothée, Guerardel, Yann, Biot, Christophe, Witters, Peter, Breckpot, Jeroen, Preston, Graem, Morava, Eva, Rujano, Maria, Cannata Serio, Magda, Panasyuk, Ganna, Reunert, Janine, Hauser, Virginie, Park, Julien, Freisinger, Peter, Guida, Maria Clara, Maier, Esther, Wada, Yoshinao, Jäger, Stefanie, Krogan, Nevan, Kretz, Oliver, Nobre, Susana, Garcia, Paula, Quelhas, Dulce, Bird, Thomas, Raskind, Wendy, Schwake, Michael, Duvet, Sandrine, Marquardt, Thorsten, Simons, Matias, Blommaert, Eline, Péanne, Romain, Cherepanova, Natalia, Rymen, Daisy, Staels, Frederik, Jaeken, Jaak, Race, Valérie, Keldermans, Liesbeth, Souche, Erika, Corveleyn, Anniek, Sparkes, Rebecca, Bhattacharya, Kaustuv, Devalck, Christine, Schrijvers, Rik, Foulquier, Francois, Gilmore, Reid, Matthijs, Gert, Université Lille Nord de France (COMUE), Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Variabilité génétique des défenses de l'organisme face à son environnement chimique, PRES Université Lille Nord de France-Université de Lille, Droit et Santé, ANR-15-CE14-0001,SOLV_CDG,Décryptage des patients CDG (Congenital Disorders of Glyvosylation) déficients en TMEM165 - de la compréhension des mécanismes moléculaires à une thérapie(2015), ANR-15-RAR3-0004,EURO-CDG-2,A European research network directed towards improving diagnosis and treatment of inborn glycosylation disorders.(2015), European Project: 643578,H2020,H2020-HCO-2014,E-Rare-3(2014), 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 National de la Recherche Agronomique (INRA)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université de Lille, CNRS, Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 [UGSF], Unité de Glycobiologie Structurale et Fonctionnelle - UMR 8576 [UGSF], Centre Hospitalier Régional Universitaire [Lille] [CHRU Lille], Impact de l'environnement chimique sur la santé humaine - ULR 4483 [IMPECS], Baylor University, University of Arkansas for Medical Sciences [UAMS], Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), 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), Institut de psychiatrie et neurosciences (U894 / UMS 1266), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Key-Obs, JRC Institute for Energy and Transport (IET), European Commission - Joint Research Centre [Petten], Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université] (INMED - INSERM U1249), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Plateforme Protéomique Necker [SFR Necker] (PPN - 3P5), Structure Fédérative de Recherche Necker (SFR Necker - UMS 3633 / US24), 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)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Impact de l'environnement chimique sur la santé humaine (IMPECS), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille, Biologie cellulaire et moléculaire de la sécrétion (BCMS), Centre National de la Recherche Scientifique (CNRS), Departamento de Bioquímica, Instituto Nacional de Enfermedades Respiratorias, Department of Experimental, Diagnostic and Specialty Medicine (DIMES) (DIMES), Università di Bologna [Bologna] (UNIBO), Laboratoire de Physique des Lasers, Atomes et Molécules - UMR 8523 (PhLAM), Biophotonique Cellulaire Fonctionelle, Institut de Recherche Interdisciplinaire, Institut de Recherche Interdisciplinaire [Villeneuve d'Ascq] (IRI), Université de Lille, Sciences et Technologies-Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Centre méditerranéen de médecine moléculaire (C3M), 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), Department of Medicine & Physiology , University of Toronto, First Faculty of Medicine, Charles University [Prague], University Medical Center [Utrecht], Department of Human Genetics, Radboud University Medical Center [Nijmegen], Paediatrics, Beatrix Children's Hospital/University Medical Center Groningen, Université Toulouse 1 Capitole (UT1), Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Chimie Moléculaire et Formulation (EA 4478), Université de Lille, Sciences et Technologies, Unité de Catalyse et de Chimie du Solide - UMR 8181 (UCCS), Université d'Artois (UA)-Ecole Centrale de Lille-Ecole Nationale Supérieure de Chimie de Lille (ENSCL)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Department of Pediatrics, University Children's Hospital, Centre de recherche Croissance et signalisation (UMR_S 845), Reutlingen University, Department of General Pediatrics, Münster University Children Hospital, Molecular Diagnostics, Center for Human Genetics, Gasthuisberg, Katholieke Universiteit Leuven and Flanders Interuniversity Institute for Biotechnology 4, Leuven, Belgium, Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Center for Human Genetics, and Laboratory of clinical immunology
Subjects: Glycosylation, Protein family, [SDV]Life Sciences [q-bio], Golgi Apparatus, FBS, manganese level, N‐glycosylation defects, TMEM165, Article, Antiporters, Glycomics, 03 medical and health sciences, chemistry.chemical_compound, symbols.namesake, Congenital Disorders of Glycosylation, 0302 clinical medicine, N-linked glycosylation, Genetics, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Cation Transport Proteins, Genetics (clinical), ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Manganese, 0303 health sciences, Ion Transport, HEK 293 cells, Serum Albumin, Bovine, Golgi apparatus, Embryonic stem cell, Cell biology, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], carbohydrates (lipids), HEK293 Cells, chemistry, symbols, Calcium, 030217 neurology & neurosurgery, Fetal bovine serum
Abstract: TMEM165 is involved in a rare genetic human disease named TMEM165‐CDG (congenital disorders of glycosylation). It is Golgi localized, highly conserved through evolution and belongs to the uncharacterized protein family 0016 (UPF0016). The use of isogenic TMEM165 KO HEK cells was crucial in deciphering the function of TMEM165 in Golgi manganese homeostasis. Manganese is a major cofactor of many glycosylation enzymes. Severe Golgi glycosylation defects are observed in TMEM165 Knock Out Human Embryonic Kidney (KO HEK) cells and are rescued by exogenous manganese supplementation. Intriguingly, we demonstrate in this study that the observed Golgi glycosylation defect mainly depends on fetal bovine serum, particularly its manganese level. Our results also demonstrate that iron and/or galactose can modulate the observed glycosylation defects in TMEM165 KO HEK cells. While isogenic cultured cells are widely used to study the impact of gene defects on proteins' glycosylation patterns, these results emphasize the importance of the use of validated fetal bovine serum in glycomics studies. 43;2
Published: 2019

27. Multivalent cationic pseudopeptide polyplexes as a tool for cancer therapy

Author: José Courty, Benoit Vallée, Ilaria Cascone, Zoi Diamantopoulou, Eric Leroy, Federica Maione, Maud-Emmanuelle Gilles, Blandine Brissault, Maha Sader, Jacques Penelle, Damien Habert, Mélissande Cossutta, Claire Houppe, Damien Destouches, Enrico Giraudo, Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Institut de Chimie et des Matériaux Paris-Est (ICMPE), and Institut de Chimie du CNRS (INC)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Biodistribution, Pancreatic ductal adenocarcinoma, Cancer therapy, Antitumour activity, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 02 engineering and technology, 03 medical and health sciences, In vivo, Pancreatic cancer, medicine, ComputingMilieux_MISCELLANEOUS, Nucleolin, business.industry, Nanoparticles, Polyplex, Oncology, Cancer, 021001 nanoscience & nanotechnology, medicine.disease, Gemcitabine, 3. Good health, 030104 developmental biology, Immunology, Cancer research, 0210 nano-technology, business, Research Paper, medicine.drug
Abstract: // Zoi Diamantopoulou 1, * , Maud-Emmanuelle Gilles 1, * , Maha Sader 1 , Melissande Cossutta 1 , Benoit Vallee 1 , Claire Houppe 1 , Damien Habert 1 , Blandine Brissault 2 , Eric Leroy 2 , Federica Maione 3 , Enrico Giraudo 3 , Damien Destouches 1 , Jacques Penelle 2 , Jose Courty 1, ** and Ilaria Cascone 1, ** 1 Laboratory of Growth, Reparation and Tissue Regeneration (CRRET), University of Paris Est, ERL-CNRS 9215, 94010 Creteil, France 2 East Paris Institute of Chemistry and Materials Science, CNRS & University Paris-Est, 94320 Thiais, France 3 Department of Oncological Sciences and Laboratory of Transgenic Mouse Models, Institute for Cancer Research and Treatment, University of Torino School of Medicine, I-10060 Candiolo, Torino, Italy * These authors have contributed equally to this work ** These authors are considered as co-senior author Correspondence to: Jose Courty, email: courty@u-pec.fr Keywords: nanoparticles, antitumour activity, polyplex, nucleolin, pancreatic ductal adenocarcinoma Received: June 21, 2017 Accepted: August 27, 2017 Published: September 30, 2017 ABSTRACT In this study, a novel anticancer reagent based on polyplexes nanoparticles was developed. These nanoparticles are obtained by mixing negatively charged polyelectrolytes with the antitumour cationically-charged pseudopeptide N6L. Using two in vivo experimental tumor pancreatic models based upon PANC-1 and mPDAC cells, we found that the antitumour activity of N6L is significantly raised via its incorporation in polyplexed nanoparticles. Study of the mechanism of action using affinity isolation and si-RNA experiments indicated that N6L-polyplexes are internalized through their interaction with nucleolin. In addition, using a very aggressive model of pancreatic cancer in which gemcitabine, a standard of care for this type of cancer, has a weak effect on tumour growth, we observed that N6L-polyplexes administration has a stronger efficacy than gemcitabine. Biodistribution studies carried out in tumour-bearing mice indicated that N6L-polyplexes localises in tumour tissue, in agreement with its antitumour effect. These results support the idea that N6L nanoparticles could develop into a promising strategy for the treatment of cancer, especially hard-to-treat pancreatic cancers.
Published: 2017

28. Des recommandations sur la prise en charge de la coxarthrose : lecture critique

Author: Xavier Chevalier, Magda Choueiri, Florent Eymard, Croissance cellulaire, réparation et régénération tissulaires (CRRET), and Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 030203 arthritis & rheumatology, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, [SDV]Life Sciences [q-bio], 030212 general & internal medicine, 3. Good health
Abstract: Resume La coxarthrose est une des pathologies osteo-articulaires les plus frequentes et les plus invalidantes. Son traitement est complexe et comporte plusieurs modalites, que le medecin doit savoir associer afin d’optimiser sa prise en charge, en veillant a la personnaliser et a l’adapter en fonction des caracteristiques propres a chaque patient. De nombreuses societes savantes se sont donc interessees a la coxarthrose et ont emis des recommandations plus ou moins specifiques a son traitement. Comme dans l’arthrose des autres articulations, notamment celle du genou a laquelle elle est souvent assimilee, il existe une grande diversite dans les interventions qui pourraient etre proposees. Toutefois, un traitement medical bien conduit se base avant toute chose sur la combinaison optimale de modalites non pharmacologiques et pharmacologiques. Il faudra, par la suite, selectionner, dans chacun de ces deux groupes, les interventions les plus adaptes au patient, ses facteurs de risque, ses comorbidites, ses moyens, ses attentes et ses demandes…C’est justement dans ce choix qu’interviennent les recommandations internationales, puisqu’elles guident le praticien dans cette tâche en contribuant a bâtir une strategie therapeutique optimale, basee sur les donnees scientifiques les plus solides du moment, ou faute de mieux, sur les opinions d’experts reconnus. Pourtant, les differentes recommandations actuellement disponibles se distinguent a bien des niveaux, laissant transparaitre quelques points d’interrogation et plusieurs sujets encore conflictuels. Il reste donc de nombreux domaines d’incertitude et de multiples points a elucider, avant de pouvoir aboutir a des recommandations qui feraient l’unanimite en beneficiant des avancees recentes dans le domaine therapeutique.
Published: 2019

29. Substrate specificity, regiospecificity, and processivity in glycoside hydrolase family 74

Author: Mohamed A. Attia, Jathavan Asohan, Alexei Savchenko, Gregory Arnal, Peter J. Stogios, Harry Brumer, Bernard Henrissat, Tatiana Skarina, Alexander Holm Viborg, Laboratoire d'Ingénierie des Systèmes Biologiques et des Procédés (LISBP), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Department of Biochemistry [University of Toronto], University of Toronto, University of British Columbia (UBC), Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Architecture et fonction des macromolécules biologiques (AFMB), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), United States Department of Energy, Office of Biological and Environmental ResearchUnited States Department of Energy (DOE) [DE-AC02-06CH11357], Savchenko, Alexei, Brumer, Harry, Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), and Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)
Subjects: Models, Molecular, 0301 basic medicine, enzyme structure-function relationships cellulase, Glycoside Hydrolases, enzyme evolution, Protein Conformation, [SDV]Life Sciences [q-bio], Context (language use), xyloglucanase, Crystallography, X-Ray, Biochemistry, Substrate Specificity, carbohydrate-active enzymes (CAZymes), 03 medical and health sciences, chemistry.chemical_compound, xyloglucan, glycobiology, Phylogenetics, Hydrolase, plant cell wall, Editors' Picks, Glycoside hydrolase, carbohydrate metabolism, Mode of action, protein evolution, Molecular Biology, molecular phylogeny, X-ray crystallography, Bacteria, 030102 biochemistry & molecular biology, glycoside hydrolase family 74 (GH74), Fungi, Stereoisomerism, Cell Biology, Processivity, hemicellulose, Xyloglucan, phylogenetics, Kinetics, polysaccharide, glycosidase, processivity, structure-function, enzyme structure-function relationships, cellulase, 030104 developmental biology, chemistry, Structural biology, processivity structure-function, Biocatalysis
Abstract: International audience; Glycoside hydrolase family 74 (GH74) is a historically important family of endo-␤-glucanases. On the basis of early reports of detectable activity on cellulose and soluble cellulose derivatives, GH74 was originally considered to be a "cellulase" family, although more recent studies have generally indicated a high specificity toward the ubiquitous plant cell wall matrix glycan xyloglucan. Previous studies have indicated that GH74 xyloglu-canases differ in backbone cleavage regiospecificities and can adopt three distinct hydrolytic modes of action: exo, endo-dis-sociative, and endo-processive. To improve functional predictions within GH74, here we coupled in-depth biochemical characterization of 17 recombinant proteins with structural biology-based investigations in the context of a comprehensive molecular phylogeny, including all previously characterized family members. Elucidation of four new GH74 tertiary structures , as well as one distantly related dual seven-bladed ␤-propeller protein from a marine bacterium, highlighted key structure-function relationships along protein evolutionary trajectories. We could define five phylogenetic groups, which delineated the mode of action and the regiospecificity of GH74 members. At the extremes, a major group of enzymes diverged to hydrolyze the backbone of xyloglucan nonspecifically with a dissociative mode of action and relaxed backbone regiospecific-ity. In contrast, a sister group of GH74 enzymes has evolved a large hydrophobic platform comprising 10 subsites, which facilitates processivity. Overall, the findings of our study refine our understanding of catalysis in GH74, providing a framework for future experimentation as well as for bioinformatics predictions of sequences emerging from (meta)genomic studies.
Published: 2019

30. The phenotype of target pancreatic cancer cells influences cell death by magnetic hyperthermia with nanoparticles carrying gemicitabine and the pseudo-peptide NucAnt

Author: Pierre Couleaud, Yuri Volkov, Adriele Prina-Mello, Alfonso Latorre, José Courty, Mourad Sanhaji, Julia Göring, Álvaro Somoza, Aitziber L. Cortajarena, Rodolfo Miranda, Ingrid Hilger, Marcus Stapf, Robert Ludwig, Antonio Aires, Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Centre for Research on Adaptive Nanostructures and Nanodevices, Trinity College Dublin, Institutfür DiagnostischeundInterventionelle RadiologieI, Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], Laboratoire CRRET, EAC/CNRS-7149, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Instituto IMDEA Nanociencia [Madrid], and Instituto Imdea Nanociencia
Subjects: Cell, Pharmaceutical Science, Medicine (miscellaneous), Apoptosis, 02 engineering and technology, Deoxycytidine, S Phase, Pancreatic tumor, Cytotoxic T cell, General Materials Science, Magnetite Nanoparticles, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, Chemistry, 021001 nanoscience & nanotechnology, 3. Good health, Tumor Burden, medicine.anatomical_structure, Phenotype, Molecular Medicine, [SDV.IB]Life Sciences [q-bio]/Bioengineering, 0210 nano-technology, medicine.drug, Programmed cell death, Biomedical Engineering, NucAnt (N6L), Mice, Nude, Bioengineering, [SDV.CAN]Life Sciences [q-bio]/Cancer, Mouse model, 03 medical and health sciences, Pancreatic cancer, Cell Line, Tumor, medicine, Animals, Humans, Magnetic hyperthermia, Gemcitabine (Gem), 030304 developmental biology, Cell Proliferation, Magnetic nanoparticles (MNP), JNK Mitogen-Activated Protein Kinases, Cell Cycle Checkpoints, Hyperthermia, Induced, medicine.disease, Xenograft Model Antitumor Assays, Gemcitabine, Pancreatic Neoplasms, Ki-67 Antigen, Cell culture, Cancer research, Peptides
Abstract: International audience; In this paper we show that conjugation of magnetic nanoparticles (MNPs) with Gemcitabine and/or NucAnt (N6L) fostered their internalization into pancreatic tumor cells and that the coupling procedure did not alter the cytotoxic potential of the drugs. By treating tumor cells (BxPC3 and PANC-1) with the conjugated MNPs and magnetic hyperthermia (43°C, 60 min), cell death was observed. The two pancreatic tumor cell lines showed different reactions against the combined therapy according to their intrinsic sensitivity against Gemcitabine (cell death, ROS production, ability to activate ERK 1/2 and JNK). Finally, tumors (e.g. 3 mL) could be effectively treated by using almost 4.2 × 10 5 times lower Gemcitabine doses compared to conventional therapies. Our data show that this combinatorial therapy might well play an important role in certain cell phenotypes with low readiness of ROS production. This would be of great significance in distinctly optimizing local pancreatic tumor treatments.
Published: 2019

31. Weibel-Palade Bodies Orchestrate Pericytes During Angiogenesis

Author: Gilles Carpentier, Emilie Picard, Fabio Raineri, Ilaria Cascone, José Courty, Cécile V. Denis, Caterina Casari, Mélissande Cossutta, Delphine Villain, Michel Paques, Benoit Vallée, Matteo Ponzo, Maud-Emmanuelle Gilles, Marie Darche, Claire Houppe, Institut Mondor de Recherche Biomédicale (IMRB), Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Institut de la Vision, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche des Cordeliers (CRC (UMR_S_1138 / U1138)), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université de Paris (UP), Neurobiologie et Psychiatrie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), Laboratoire CRRET, EAC/CNRS-7149, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Paris Cité (UPCité)
Subjects: 0301 basic medicine, Vascular Endothelial Growth Factor A, Angiogenesis, [SDV]Life Sciences [q-bio], Neovascularization, Physiologic, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Exocytosis, Retina, Angiopoietin-2, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, Von Willebrand factor, Neoplasms, Organelle, Weibel–Palade body, Animals, Humans, ComputingMilieux_MISCELLANEOUS, Cells, Cultured, biology, Neovascularization, Pathologic, Weibel-Palade Bodies, Chemistry, Angiopoietin 2, Endothelial Cells, Cell biology, Vascular endothelial growth factor, Endothelial stem cell, Mice, Inbred C57BL, 030104 developmental biology, 030220 oncology & carcinogenesis, cardiovascular system, biology.protein, Cardiology and Cardiovascular Medicine, Pericytes
Abstract: Objective Weibel-Palade bodies (WPBs) are endothelial cell (EC)-specific organelles formed by vWF (von Willebrand factor) polymerization and that contain the proangiogenic factor Ang-2 (angiopoietin-2). WPB exocytosis has been shown to be implicated for vascular repair and inflammatory responses. Here, we investigate the role of WPBs during angiogenesis and vessel stabilization. Approach and Results WPB density in ECs decreased at the angiogenic front of retinal vascular network during development and neovascularization compared with stable vessels. In vitro, VEGF (vascular endothelial growth factor) induced a VEGFR-2 (vascular endothelial growth factor receptor-2)-dependent exocytosis of WPBs that contain Ang-2 and consequently the secretion of vWF and Ang-2. Blocking VEGF-dependant WPB exocytosis and Ang-2 secretion promoted pericyte migration toward ECs. Pericyte migration was inhibited by adding recombinant Ang-2 or by silencing Ang-1 (angiopoietin-1) or Tie2 (angiopoietin-1 receptor) in pericytes. Consistently, in vivo anti-VEGF treatment induced accumulation of WPBs in retinal vessels because of the inhibition of WPB exocytosis and promoted the increase of pericyte coverage of retinal vessels during angiogenesis. In tumor angiogenesis, depletion of WPBs in vWF knockout tumor-bearing mice promoted an increase of tumor angiogenesis and a decrease of pericyte coverage of tumor vessels. By another approach, normalized tumor vessels had higher WPB density. Conclusions We demonstrate that WPB exocytosis and Ang-2 secretion are regulated during angiogenesis to limit pericyte coverage of remodeling vessels by disrupting Ang-1/Tie2 autocrine signaling in pericytes.
Published: 2019

32. Pioneer Factors and Architectural Proteins Mediating Embryonic Expression Signatures in Cancer

Author: Stephanie Dobersch, Karla Rubio, Guillermo Barreto, Max Planck Institute for Heart and Lung Research (MPI-HLR), Max-Planck-Gesellschaft, Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Université Paris-Est (UPE), Kazan Federal University (KFU), Justus-Liebig-Universität Gießen (JLU), and Justus-Liebig-Universität Gießen = Justus Liebig University (JLU)
Subjects: 0301 basic medicine, Epithelial-Mesenchymal Transition, [SDV]Life Sciences [q-bio], Biology, Genome, Malignant transformation, Histones, 03 medical and health sciences, 0302 clinical medicine, Neoplasms, Gene expression, Biomarkers, Tumor, medicine, Animals, Humans, Molecular Biology, Gene, Gene Expression Profiling, Cancer, medicine.disease, Embryonic stem cell, Chromatin, Nucleosomes, 3. Good health, Cell biology, Review article, Gene Expression Regulation, Neoplastic, 030104 developmental biology, Disease Progression, Molecular Medicine, Disease Susceptibility, 030217 neurology & neurosurgery
Abstract: International audience; Accumulation of mutations causing aberrant changes in the genome promotes cancer. However, mutations do not occur in every cancer subtype, suggesting additional events that trigger cancer. Chromatin rearrangements initiated by pioneer factors and architectural proteins are key events occurring before cancer-related genes are expressed. Both protein groups are also master regulators of important processes during embryogenesis. Several publications demonstrated that embryonic gene expression signatures are reactivated during cancer. This review article highlights current knowledge on pioneer factors and architectural proteins mediating chromatin rearrangements, which are the backbone of embryonic expression signatures promoting malignant transformation. Understanding chromatin rearrangements inducing embryonic expression signatures in adult cells might be the key to novel therapeutic approaches against cancers subtypes that arise without genomic mutations.
Published: 2019

33. A new human pyridinium metabolite of furosemide, inhibitor of mitochondrial complex I, is a candidate inducer of neurodegeneration

Author: Sonia Lehri-Boufala, Christophe Morin, Céline Laurencé, Michael Rivard, Philippe Le Corvoisier, Isabelle Lachaise, Thierry Martens, Laure Garrigue-Antar, Narimane Zeghbib, Caroline Barau, Institut de Chimie et des Matériaux Paris-Est (ICMPE), Institut de Chimie du CNRS (INC)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Service d'hépato-gastro-entérologie [APHP Henri Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), CIC - CHU Henri Mondor, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), laboratoire Eau Environnement et Systèmes Urbains (LEESU), AgroParisTech-École des Ponts ParisTech (ENPC)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Centre National de la Recherche Scientifique (CNRS)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: 0301 basic medicine, Male, endocrine system diseases, [SDV]Life Sciences [q-bio], Metabolite, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Apoptosis, Pyridinium Compounds, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Mitochondrion, Pharmacology, Biochemistry, Nervous System, chemistry.chemical_compound, Mice, 0302 clinical medicine, Furosemide, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], ComputingMilieux_MISCELLANEOUS, Molecular Structure, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Chemistry, Neurodegeneration, Middle Aged, 3. Good health, Mitochondria, 030220 oncology & carcinogenesis, Toxicity, Female, medicine.symptom, medicine.drug, 03 medical and health sciences, Oxygen Consumption, [SDV.SP.MED]Life Sciences [q-bio]/Pharmaceutical sciences/Medication, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, In vivo, Cell Line, Tumor, medicine, Animals, Humans, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Aged, Electron Transport Complex I, Tyrosine hydroxylase, medicine.disease, 030104 developmental biology, Mechanism of action, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Reactive Oxygen Species
Abstract: International audience; Pharmaceuticals and their by-products are increasingly a matter of concern, because of their unknown impacts on human health and ecosystems. The lack of information on these transformation products, which toxicity may exceed that of their parent molecules, makes their detection and toxicological evaluation impossible.Recently we characterized the Pyridinium of furosemide (PoF), a new transformation product of furosemide, the most widely used diuretic and an emerging pollutant. Here, we reveal PoF toxicity in SH-SY5Y cells leading to alpha-synuclein accumulation, reactive oxygen species generation, and apoptosis. We also showed that its mechanism of action is mediated through specific inhibition of striatal respiratory chain complex I, both in vitro by direct exposure of striatum mitochondria to PoF, and in vivo, in striatal mitochondria isolated from mice exposed to PoF for 7 days in drinking water and sacrificed 30 days later. Moreover, in mice, PoF induced neurodegenerative diseases hallmarks like phospho-Serine129 alpha-synuclein, tyrosine hydroxylase decrease in striatum, Tau accumulation in hippocampus. Finally, we uncovered PoF as a new metabolite of furosemide present in urine of patients treated with this drug by LC/MS. As a physiopathologically relevant neurodegeneration inducer, this new metabolite warrants further studies in the framework of public health and environment protection.
Published: 2019

34. Impact du traitement par statines dans la progression radiologique de la gonarthrose : résultats issus de l’analyse post-hoc de l’essai SEKOIA

Author: Florent Eymard, Jean-Yves Reginster, Mark H. Edwards, Olivier Bruyère, F Petit-Dop, Camille Parsons, Xavier Chevalier, Cyrus Cooper, Pascal Richette, Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques (BIOSCAR (UMR_S_1132 / U1132)), and Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 030203 arthritis & rheumatology, 03 medical and health sciences, 0302 clinical medicine, Rheumatology, [SDV]Life Sciences [q-bio], 030212 general & internal medicine, 3. Good health
Abstract: Resume Objectifs Les etudes epidemiologiques et fondamentales suggerent que les desordres lipidiques puissent etre impliques dans la physiopathologie de la gonarthrose. Les diverses etudes ayant evalue l’effet des statines ont montre des resultats contradictoires. Nous avons etudie l’effet des statines sur la progression radiologique chez des patients atteints d’une gonarthrose symptomatique confirmee sur les radiographies. Methodes 336 patients issus du groupe placebo de l’essai SEKOIA ont complete les 3 ans de suivi et ont ete inclus dans cette analyse post-hoc. La prise de statines etait evaluee lors de la visite d’inclusion. La mesure de l’interligne articulaire femorotibiale minimale etait effectuee sur des radiographies standards selon une methode automatisee a l’inclusion puis de facon annuelle. La progression radiologique etait definie comme un pincement ≥ 0,5 mm sur 3 ans. Resultats 71 patients etaient sous statines (21,1 %). Comparativement aux sujets non traites, ils avaient un BMI superieur (31,1 ± 5,3 vs. 29,3 ± 5,2 kg/m2, p = 0,008) et un plus grand nombre de facteurs metaboliques (≥ 3 facteurs : 43,7 % vs. 7,2 % ; pet 30 kg/m2) et des maladies cardiovasculaires [risque relatif 1,49 (IC95 % 1,10–2,02), pet = 0,010]. Conclusion Chez les patients ayant une gonarthrose symptomatique, l’utilisation de statines etait associee a une plus grande progression radiologique independamment des facteurs confondants (obesite, diabete de type 2, hypertension, duree de la maladie, intensite des symptomes et severite radiologique).
Published: 2019

35. Glycosaminoglycans from Alzheimer’s disease hippocampus have altered capacities to bind and regulate growth factors activities and to bind tau

Author: Rita Raisman-Vozari, Joao Vilares, Gilles Carpentier, Mohand Ouidir Ouidja, Dulce Papy-Garcia, Auriane Maïza, Sandrine Chantepie, Ganlin Zhang, Minh Bao Huynh, Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Federal University of Sao Paulo (Unifesp), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], and Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Male, Vascular Endothelial Growth Factor A, Physiology, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Plasma protein binding, Hippocampus, Extracellular matrix, Glycosaminoglycan, chemistry.chemical_compound, Binding Analysis, 0302 clinical medicine, Sulfation, Endocrinology, Medicine and Health Sciences, Homeostasis, Enzyme-linked immunoassays, Tissue homeostasis, Glycosaminoglycans, Aged, 80 and over, Multidisciplinary, Chemistry, Chondroitin Sulfates, Chemical Reactions, Brain, Drugs, Neurodegenerative Diseases, Heparin, Middle Aged, Alzheimer's disease, Temporal Lobe, Cell biology, Extracellular Matrix, Neurology, Physical Sciences, Medicine, Female, Fibroblast Growth Factor 2, Anatomy, Growth factors, Brazil, medicine.drug, Research Article, Protein Binding, Science, tau Proteins, Research and Analysis Methods, DNA-binding protein, 03 medical and health sciences, Cell binding assay, Alzheimer Disease, Mental Health and Psychiatry, medicine, Chondroitin, Humans, Immunoassays, Chemical Characterization, Aged, Pharmacology, Endocrine Physiology, Brain-Derived Neurotrophic Factor, Biology and Life Sciences, 030104 developmental biology, Immunologic Techniques, Dementia, Heparitin Sulfate, Physiological Processes, 030217 neurology & neurosurgery
Abstract: International audience; Glycosaminoglycans (GAGs), including heparan sulfates and chondroitin sulfates, are major components of the extracellular matrix. Upon interacting with heparin binding growth factors (HBGF), GAGs participate to the maintaintenance of tissue homeostasis and contribute to self-healing. Although several processes regulated by HBGF are altered in Alzheimer’s disease, it is unknown whether the brain GAG capacities to bind and regulate the function of HBGF or of other heparin binding proteins, as tau, are modified in this disease. Here, we show that total sulfated GAGs from hippocampus of Alzheimer’s disease have altered capacities to bind and potentiate the activities of growth factors including FGF-2, VEGF, and BDNF while their capacity to bind to tau is remarkable increased. Alterations of GAG structures and capacities to interact with and regulate the activity of heparin binding proteins might contribute to impaired tissue homeostasis in the Alzheimer’s disease brain.
Published: 2019

36. Implication of NPM1 phosphorylation and preclinical evaluation of the nucleoprotein antagonist N6L in prostate cancer

Author: Francis Vacherot, Charles Marchand, Jocelyn Céraline, Damien Destouches, Fannie Semprez, José Courty, Gilles Carpentier, Pascale Maillé, Pascale Soyeux, Stéphane Terry, Yves Allory, Maha Sader, Alexandre de la Taille, Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Oncogénèse des tumeurs respiratoires et urogénitales, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Altération génétique des cancers, chimioprévention et réponse thérapeutique, Laboratoire CRRET, EAC/CNRS-7149, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service d'urologie [Mondor], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: Male, Threonine, 0301 basic medicine, Angiogenesis, Docetaxel, urologic and male genital diseases, Prostate cancer, 0302 clinical medicine, Prostate, androgen receptor, Medicine, Phosphorylation, ComputingMilieux_MISCELLANEOUS, N6L, Nuclear Proteins, prostate cancer, phosphorylated NPM1, Tumor Burden, 3. Good health, Prostatic Neoplasms, Castration-Resistant, medicine.anatomical_structure, Oncology, Receptors, Androgen, 030220 oncology & carcinogenesis, Taxoids, NPM1, Nucleophosmin, Protein Binding, Research Paper, medicine.drug, Mice, Nude, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, In vivo, Cell Line, Tumor, Animals, Humans, business.industry, Prostatic Neoplasms, medicine.disease, Xenograft Model Antitumor Assays, Androgen receptor, Nucleoproteins, 030104 developmental biology, Immunology, Cancer research, Peptides, business
Abstract: Despite the advent of several new treatment options over the past years, advanced/metastatic prostate carcinoma (PCa) still remains incurable, which justifies the search for novel targets and therapeutic molecules. Nucleophosmin (NPM1) is a shuttling nucleoprotein involved in tumor growth and its targeting could be a potential approach for cancer therapy. We previously demonstrated that the multivalent pseudopeptide N6L binds to NPM1 potently affecting in vitro and in vivo tumor cell growth of various tumor types as well as angiogenesis. Furthermore, NPM1 binds to androgen receptor (AR) and modulate its activity. In this study, we first investigated the implication of the NPM1 and its Thr199 and Thr234/237 phosphorylated forms in PCa. We showed that phosphorylated forms of NPM1 interact with androgen receptor (AR) in nucleoplasm. N6L treatment of prostate tumor cells led to inhibition of NPM1 phosphorylation in conjunction with inhibition of AR activity. We also found that total and phosphorylated NPM1 were overexpressed in castration-resistant PCa. Assessment of the potential therapeutic role of N6L in PCa indicated that N6L inhibited tumor growth both in vitro and in vivo when used either alone or in combination with the standard-of-care first- (hormonotherapy) and second-line (docetaxel) treatments for advanced PCa. Our findings reveal the role of Thr199 and Thr234/237 phosphorylated NPM1 in PCa progression and define N6L as a new drug candidate for PCa therapy.
Published: 2016

37. Nucleolin antagonist triggers autophagic cell death in human glioblastoma primary cells and decreased in vivo tumor growth in orthotopic brain tumor model

Author: Benedetta Cinque, Annamaria Cimini, Rodolfo Ippoliti, José Courty, Anne Chloe Dhez, Loredana Cristiano, Michele d'Angelo, Andrea Antonosante, Floriana Rosati, Renato Galzio, Antonio Giordano, Damien Destouches, Alessia Fidoamore, Carlo Astarita, T. Florio, Elisabetta Benedetti, Maria Grazia Cifone, Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Dipartimento di Biologia di Base ed Applicata, Università degli Studi dell'Aquila (UNIVAQ), Laboratoire CRRET, EAC/CNRS-7149, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Università degli Studi dell'Aquila = University of L'Aquila (UNIVAQ)
Subjects: Pathology, medicine.medical_treatment, Nude, Autophagy, Glioblastoma, Targeted therapy, Oncology, Kaplan-Meier Estimate, Mice, 0302 clinical medicine, Tumor Cells, Cultured, Inbred BALB C, ComputingMilieux_MISCELLANEOUS, Microscopy, 0303 health sciences, Mice, Inbred BALB C, Tumor, Cultured, Brain Neoplasms, RNA-Binding Proteins, Drug Synergism, Middle Aged, targeted therapy, Alkylating, Tumor Cells, 3. Good health, Tumor Burden, Dacarbazine, 030220 oncology & carcinogenesis, Female, Research Paper, Adult, Programmed cell death, medicine.medical_specialty, autophagy, Cell Survival, Brain tumor, Mice, Nude, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, Aged, Animals, Antineoplastic Agents, Alkylating, Cell Line, Tumor, Cell Proliferation, G1 Phase Cell Cycle Checkpoints, Humans, Microscopy, Fluorescence, Peptides, Phosphoproteins, Xenograft Model Antitumor Assays, Biology, Fluorescence, Cell Line, 03 medical and health sciences, Cyclin D1, In vivo, medicine, Temozolomide, glioblastoma, 030304 developmental biology, Cell growth, medicine.disease, Cancer research, Nucleolin
Abstract: Nucleolin (NCL) is highly expressed in several types of cancer and represents an interesting therapeutic target. It is expressed at the plasma membrane of tumor cells, a property which is being used as a marker for several human cancer including glioblastoma. In this study we investigated targeting NCL as a new therapeutic strategy for the treatment of this pathology. To explore this possibility, we studied the effect of an antagonist of NCL, the multivalent pseudopeptide N6L using primary culture of human glioblastoma cells. In this system, N6L inhibits cell growth with different sensitivity depending to NCL localization. Cell cycle analysis indicated that N6L-induced growth reduction was due to a block of the G1/S transition with down-regulation of the expression of cyclin D1 and B2. By monitoring autophagy markers such as p62 and LC3II, we demonstrate that autophagy is enhanced after N6L treatment. In addition, N6L-treatment of mice bearing tumor decreased in vivo tumor growth in orthotopic brain tumor model and increase mice survival. The results obtained indicated an anti-proliferative and pro-autophagic effect of N6L and point towards its possible use as adjuvant agent to the standard therapeutic protocols presently utilized for glioblastoma.
Published: 2015

38. Recognition of breathprints of lung cancer and chronic obstructive pulmonary disease using the Aeonose® electronic nose

Author: Maria Degen, Jana Haberer, Werner Seeger, Andreas Guenther, Guillermo Barreto, Ekaterina Krauss, University of Giessen and Marburg Lung Center [Gießen, Germany] (UGMLC), European IPF Registry and Biobank (eurIPFreg/bank), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Max Planck Institute for Heart and Lung Research (MPI-HLR), Max-Planck-Gesellschaft, Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), and Agaplesion Pneumologische KliniK Waldhof-Elgershausen
Subjects: Pulmonary and Respiratory Medicine, medicine.medical_specialty, COPD, Electronic nose, business.industry, [SDV]Life Sciences [q-bio], 010401 analytical chemistry, Case-control study, Complete remission, Pulmonary disease, medicine.disease, 01 natural sciences, Gastroenterology, 3. Good health, 0104 chemical sciences, Unmet needs, Clinical trial, 03 medical and health sciences, 0302 clinical medicine, 030228 respiratory system, Internal medicine, medicine, Lung cancer, business
Abstract: International audience; Objectives: There is a high unmet need in a non-invasive screening of lung cancer (LC). We conducted this single-center trial to evaluate the effectiveness of the electronic nose Aeonose ® in LC recognition.Materials and methods: Exhaled volatile organic compound (VOC) signatures were collected by Aeonose ® in 42 incident and 78 prevalent LC patients, of them 29 LC patients in complete remission (LC CR), 33 healthy controls (HC) and 23 COPD patients. By dichotomous comparison of VOC's between incident LC and HC, a discriminating algorithm was established and also applied to LC CR and COPD subjects. Area under Curve (AUC), sensitivity, specificity and Matthews's correlation coefficient (MC) were used to interpret the data.Results: The established algorithm of Aeonose ® signature allowed safe separation of LC and HC, showing an AUC of 0.92, sensitivity of 0.84 and a specificity of 0.97. When tested in a blinded fashion, the device recognized 19 out of 29 LC CR patients (=65.5%) as LC-positive, of which only five developed recurrent LC later on (after 18.6 months [Formula: see text]; mean value [Formula: see text]). Unfortunately, the algorithm also recognized 11 of 24 COPD patients as being LC positive (with only one of the 24 COPD patients developing LC 56 months after the measurement).Conclusion: The Aeonose ® revealed some potential in distinguishing LC from HC, however, with low specificity when applying the algorithm in a blinded fashion to other disease cohorts. We conclude that relevant VOC signals originating from comorbidities in LC such as COPD may have erroneously led to the separation between LC and controls.Clinical trial registration: (NCT02951416).
Published: 2020

39. Heparan sulfate 3- O -sulfotransferase 2 (HS3ST2) displays an unexpected subcellular localization in the plasma membrane

Author: François Foulquier, Dorothée Vicogne, Fabrice Allain, Maxime Delos, Charles Hellec, Mathieu Carpentier, Dulce Papy-Garcia, Alexandre Fifre, Agnès Denys, Unité de Glycobiologie Structurale et Fonctionnelle UMR 8576 (UGSF), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), and Université de Lille-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Sulfotransferase, Cell, Biophysics, Glycobiology, Golgi Apparatus, Heparan sulfate, Real-Time Polymerase Chain Reaction, Biochemistry, Isozyme, Monocytes, Amidohydrolases, 03 medical and health sciences, chemistry.chemical_compound, symbols.namesake, medicine, Humans, RNA, Small Interfering, Molecular Biology, Cells, Cultured, biology, Subcellular localization, Macrophages, Cell Membrane, Membrane Proteins, Golgi apparatus, Cell biology, Isoenzymes, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, 030104 developmental biology, medicine.anatomical_structure, HEK293 Cells, chemistry, Proteoglycan, Microscopy, Fluorescence, biology.protein, symbols, Sulfotransferases, Syndecan-2, Immunostaining, HeLa Cells, Subcellular Fractions
Abstract: Background Heparan sulfate (HS) 3-O-sulfation can be catalysed by seven 3-O-sulfotransferases (HS3STs) in humans, still it is the rarest modification in HS and its biological function is yet misunderstood. HS3ST2 and HS3ST3B exhibit the same activity in vitro. They are however differently expressed in macrophages depending on cell environment, which suggests that they may be involved in distinct cellular processes. Here, we hypothesized that both isozymes might also display distinct subcellular localizations. Methods The subcellular distribution of HS3ST2 and HS3ST3B was analysed by using overexpression systems in HeLa cells. The localization of endogenous HS3ST2 was confirmed by immunostaining in primary macrophages. Results We found that HS3ST3B was only localized in the Golgi apparatus and no difference between full-length enzyme and truncated construct depleted of its catalytic domain was observed. In contrast, HS3ST2 was clearly visualized at the plasma membrane. Its truncated form remained in the Golgi apparatus, meaning that the catalytic domain might support correct addressing of HS3ST2 to cell surface. Moreover, we found a partial co-localization of HS3ST2 with syndecan-2 in HeLa cells and primary macrophages. Silencing the expression of this proteoglycan altered the localization of HS3ST2, which suggests that syndecan-2 is required to address the isozyme outside of the Golgi apparatus. Conclusions We demonstrated that HS3ST3B is a Golgi-resident isozyme, while HS3ST2 is addressed to the plasma membrane with syndecan-2. General significance The membrane localization of HS3ST2 suggests that this enzyme may participate in discrete processes that occur at the cell surface.
Published: 2018

40. Exploring the Ability of Electronic Nose Technology to Recognize Interstitial Lung Diseases (ILD) by Non-Invasive Breath Screening of Exhaled Volatile Compounds (VOC): A Pilot Study from the European IPF Registry (eurIPFreg) and Biobank

Author: Jana Haberer, Guillermo Barreto, Ekaterina Krauss, Maria Degen, Werner Seeger, Olga Maurer, Andreas Guenther, Fotios Drakopanagiotakis, University of Giessen and Marburg Lung Center [Gießen, Germany] (UGMLC), European IPF Registry and Biobank (eurIPFreg/bank), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Max Planck Institute for Heart and Lung Research (MPI-HLR), Max-Planck-Gesellschaft, Croissance cellulaire, réparation et régénération tissulaires (CRRET), and Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Oncology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], lcsh:Medicine, electronic nose (enose, aeonose®), behavioral disciplines and activities, Article, Unmet needs, 03 medical and health sciences, Idiopathic pulmonary fibrosis, 0302 clinical medicine, interstitial lung diseases (ILD), Internal medicine, medicine, COPD, Lung, Electronic nose, business.industry, European Registry for Idiopathic Pulmonary Fibrosis (eurIPFreg), lcsh:R, electronic Nose (eNose, Aeonose®), Non invasive, Area under the curve, General Medicine, respiratory system, medicine.disease, volatile organic compounds (VOC), respiratory tract diseases, 3. Good health, body regions, medicine.anatomical_structure, 030228 respiratory system, 030220 oncology & carcinogenesis, idiopathic pulmonary fibrosis (IPF), business, Cryptogenic Organizing Pneumonia
Abstract: Background: There is an increasing interest in employing electronic nose technology in the diagnosis and monitoring of lung diseases. Interstitial lung diseases (ILD) are challenging in regard to setting an accurate diagnosis in a timely manner. Thus, there is a high unmet need in non-invasive diagnostic tests. This single-center explorative study aimed to evaluate the usefulness of electronic nose (Aeonose&reg, ) in the diagnosis of ILDs. Methods: Exhaled volatile organic compound (VOC) signatures were obtained by Aeonose&reg, in 174 ILD patients, 23 patients with chronic obstructive pulmonary disease (COPD), and 33 healthy controls (HC). Results: By dichotomous comparison of VOC&rsquo, s between ILD, COPD, and HC, a discriminating algorithm was established. In addition, direct analyses between the ILD subgroups, e.g., cryptogenic organizing pneumonia (COP, n = 28), idiopathic pulmonary fibrosis (IPF, n = 51), and connective tissue disease-associated ILD (CTD-ILD, n = 25) were performed. Area under the Curve (AUC) and Matthews&rsquo, s correlation coefficient (MCC) were used to interpret the data. In direct comparison of the different ILD subgroups to HC, the algorithms developed on the basis of the Aeonose&reg, signatures allowed safe separation between IPF vs. HC (AUC of 0.95, MCC of 0.73), COP vs. HC (AUC 0.89, MCC 0.67), and CTD-ILD vs. HC (AUC 0.90, MCC 0.69). Additionally, to a case-control study design, the breath patterns of ILD subgroups were compared to each other. Following this approach, the sensitivity and specificity showed a relevant drop, which results in a poorer performance of the algorithm to separate the different ILD subgroups (IPF vs. COP with MCC 0.49, IPF vs. CTD-ILD with MCC 0.55, and COP vs. CT-ILD with MCC 0.40). Conclusions: The Aeonose&reg, showed some potential in separating ILD subgroups from HC. Unfortunately, when applying the algorithm to distinguish ILD subgroups from each other, the device showed low specificity. We suggest that artificial intelligence or principle compound analysis-based studies of a much broader data set of patients with ILDs may be much better suited to train these devices.
Published: 2019

41. On the Chemical Abundances of Miras in Clusters: V1 in the Metal-rich Globular NGC 5927

Author: Bertrand Lemasle, Chikako Yasui, M. Fabrizio, M. Marengo, Nicoletta Sanna, R. Buonanno, S. S. Elgueta, G. Iannicola, Ayaka Watase, Akira Arai, D. Magurno, Martino Romaniello, P. Francois, Jillian R. Neeley, Hiroaki Sameshima, Satoshi Hamano, Mingjie Jian, Noriyuki Matsunaga, Takuji Tsujimoto, Yuji Ikeda, Bastian Proxauf, Maria Bergemann, R. da Silva, Giuseppe Bono, I. Ferraro, R. P. Kudritzki, Dante Minniti, Shogo Otsubo, Naoto Kobayashi, Christopher Sneden, F. Thévenin, Massimo Dall'Ora, Roberto Gilmozzi, M. Urbaneja-Perez, Norbert Przybilla, T. Yoshikawa, J. L. Prieto, S. Marinoni, Ivo Saviane, Giuliana Fiorentino, Hideyo Kawakita, Sohei Kondo, Vittorio F. Braga, Elena Valenti, Manuela Zoccali, Valentina D'Orazi, Laura Inno, Keiichi Takenaka, Mario Nonino, Daisuke Taniguchi, Kei Fukue, M. Monelli, C. E. Martínez-Vázquez, D'Orazi, V., Magurno, D., Bono, G., Matsunaga, N., Braga, V.F., Elgueta, S.S., Fukue, K., Hamano, S., Inno, L., Kobayashi, N., Kondo, S., Monelli, M., Nonino, M., Przybilla, N., Sameshima, H., Saviane, I., Taniguchi, D., Thevenin, F., Urbaneja-Perez, M., Watase, A., Arai, A., Bergemann, M., Buonanno, R., Dall'Ora, M., Da Silva, R., Fabrizio, M., Ferraro, I., Fiorentino, G., Francois, P., Gilmozzi, R., Iannicola, G., Ikeda, Y., Jian, M., Kawakita, H., Kudritzki, R.P., Lemasle, B., Marengo, M., Marinoni, S., Martínez-Vázquez, C.E., Minniti, D., Neeley, J., Otsubo, S., Prieto, J.L., Proxauf, B., Romaniello, M., Sanna, N., Sneden, C., Takenaka, K., Tsujimoto, T., Valenti, E., Yasui, C., Yoshikawa, T., Zoccali, M., INAF - Osservatorio Astronomico di Padova (OAPD), Istituto Nazionale di Astrofisica (INAF), Department of Mechanical System Engineering, Takushoku University, Department of Physics [Tokyo], Tokyo Institure of Technology, INAF - Osservatorio Astronomico di Trieste (OAT), Joseph Louis LAGRANGE (LAGRANGE), Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Observatoire de la Côte d'Azur, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Scuola Internazionale Superiore di Studi Avanzati / International School for Advanced Studies (SISSA / ISAS), Galaxies, Etoiles, Physique, Instrumentation (GEPI), Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Kapteyn Astronomical Institute [Groningen], University of Groningen [Groningen], Sciences pour l'environnement (SPE), Centre National de la Recherche Scientifique (CNRS)-Université Pascal Paoli (UPP), Universidad Andrés Bello [Santiago] (UNAB), Instituto de Sistemas Optoelectrónicos y Microtecnología, Universidad Politécnica de Madrid (UPM), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de la Côte d'Azur, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Pascal Paoli (UPP)-Centre National de la Recherche Scientifique (CNRS), and Henry, Florence
Subjects: stars: abundances, globular clusters: individual (NGC 5927), individual (NGC 5927) [Globular clusters], Metallicity, Analytical chemistry, FOS: Physical sciences, 01 natural sciences, Spectral line, variables: general [Stars], Settore FIS/05 - Astronomia e Astrofisica, Abundance (ecology), 0103 physical sciences, Cluster (physics), stars: variables: general, 010303 astronomy & astrophysics, Solar and Stellar Astrophysics (astro-ph.SR), ComputingMilieux_MISCELLANEOUS, Physics, Mira variable, 010308 nuclear & particles physics, Astronomy and Astrophysics, Effective temperature, Astronomy and Astrophysic, Surface gravity, stars: abundance, Astrophysics - Solar and Stellar Astrophysics, Space and Planetary Science, Globular cluster, abundances [Stars], [PHYS.ASTR] Physics [physics]/Astrophysics [astro-ph], [PHYS.ASTR]Physics [physics]/Astrophysics [astro-ph]
Abstract: We present the first spectroscopic abundance determination of iron, alpha-elements (Si, Ca and Ti) and sodium for the Mira variable V1 in the metal-rich globular cluster NGC 5927. We use high-resolution (R~ 28,000), high signal-to-noise ratio (~200) spectra collected with WINERED, a near-infrared (NIR) spectrograph covering simultaneously the wavelength range 0.91--1.35 micron. The effective temperature and the surface gravity at the pulsation phase of the spectroscopic observation were estimated using both optical (V) and NIR time-series photometric data. We found that the Mira is metal-rich ([Fe/H]=-0.55 \pm 0.15) and moderately alpha-enhanced ([alpha/Fe]=0.15 \pm 0.01, sigma=0.2). These values agree quite well with the mean cluster abundances based on high-resolution optical spectra of several cluster red giants available in the literature ([Fe/H]=-0.47 \pm 0.06, [alpha/Fe]=+0.24 \pm 0.05). We also found a Na abundance of +0.35 \pm 0.20 that is higher than the mean cluster abundance based on optical spectra (+0.18 \pm 0.13). However, the lack of similar spectra for cluster red giants and that of corrections for departures from local-thermodynamical equilibrium prevents us from establishing whether the difference is intrinsic or connected with multiple populations. These findings indicate a strong similarity between optical and NIR metallicity scales in spite of the difference in the experimental equipment, data analysis and in the adopted spectroscopic diagnostics., Comment: Accepted for publication in the Astrophysical Journal Letters, 9 pages, 3 figures
Published: 2018

42. Targeted therapy of human glioblastoma via delivery of a toxin through a peptide directed to cell surface nucleolin

Author: Loredana Cristiano, Andrea Antonosante, Renato Galzio, Anne Chloe Dhez, Marina Melone, Elisabetta Benedetti, Luana Di Leandro, Luca Federici, Michele d'Angelo, Francesco Angelucci, Annamaria Cimini, Gloria Panella, Fabio Raineri, José Courty, T. Florio, Francesco Giansanti, Rodolfo Ippoliti, Antonella De Cola, Ilaria Cascone, Brigida Ranieri, Antonio Giordano, Department of Biochemical Sciences 'Rossi Fanelli', Institut Pasteur, Fondation Cenci Bolognetti - Istituto Pasteur Italia, Fondazione Cenci Bolognetti, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Dipartimento di Biologia di Base e Applicata, Università degli Studi dell'Aquila (UNIVAQ), Dipartimento Sci Biochim, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Laboratoire CRRET, EAC/CNRS-7149, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Dipartimento di Biologia di Base ed Applicata, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Università degli Studi dell'Aquila = University of L'Aquila (UNIVAQ), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Dhez, A, Benedetti, E, Antonosante, A, Panella, G, Ranieri, B, Florio, T, Cristiano, L, Angelucci, F, Giansanti, F, Di Leandro, L, D'Angelo, M, Melone, Ma, De Cola, A, Federici, L, Galzio, R, Cascone, I, Raineri, F, Cimini, A, Courty, J, Giordano, A, and Ippoliti, R.
Subjects: 0301 basic medicine, glioblastoma, NucAnt (N6L), nucleolin, saporin, targeted therapy, Physiology, Clinical Biochemistry, Cell Biology, Saporin, medicine.medical_treatment, media_common.quotation_subject, Cell, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Targeted therapy, Mice, 03 medical and health sciences, 0302 clinical medicine, In vivo, Cell Line, Tumor, medicine, Animals, Humans, Molecular Targeted Therapy, Internalization, ComputingMilieux_MISCELLANEOUS, Cell Proliferation, media_common, Neovascularization, Pathologic, Cell Membrane, RNA-Binding Proteins, Phosphoproteins, Saporins, Xenograft Model Antitumor Assays, Molecular biology, Nucleolin, In vitro, 3. Good health, 030104 developmental biology, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Cancer cell, Cancer research, biology.protein, Peptides
Abstract: Targeted anticancer therapies demand discovery of new cellular targets to be exploited for the delivery of toxic molecules and drugs. In this perspective, in the last few years, nucleolin has been identified as an interesting surface marker to be used for the therapy of glioblastoma. In this study, we investigated whether a synthetic antagonist of cell-surface nucleolin known as N6L, previously reported to decrease both tumour growth and tumour angiogenesis in several cancer cell lines, including glioblastoma cells, as well as endothelial cells proliferation, could be exploited to deliver a protein toxin (saporin) to glioblastoma cells. The pseudopeptide N6L cross-linked to saporin-S6 induced internalization of the toxin inside glioblastoma cancer cells. Our results in vitro demonstrated the effectiveness of this conjugate in inducing cell death, with an ID50 four orders of magnitude lower than that observed for free N6L. Furthermore, the preliminary "in vivo" study demonstrated efficiency in reducing the tumour mass in an orthotopic mouse model of glioblastoma
Published: 2018

43. Muscle satellite cells are functionally impaired in myasthenia gravis: consequences on muscle regeneration

Author: Marie Maurer, Marieke Robinet, Gillian Butler-Browne, Rozen Le Panse, Elie Fadel, Fabien Le Grand, Mohamed F. Attia, Sonia Berrih-Aknin, Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Génétique Moléculaire et Cellulaire (UGMC), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Centre de recherche en 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)-Université Pierre et Marie Curie - Paris 6 (UPMC), 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), Hypertension arterielle pulmonaire physiopathologie et innovation thérapeutique, Centre chirurgical Marie Lannelongue-Institut National de la Santé et de la Recherche Médicale (INSERM), 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) (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), Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Descartes - Paris 5 (UPD5)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC), Université Pierre et Marie Curie - Paris 6 (UPMC)-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), 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), Centre Chirurgical Marie Lannelongue (CCML), Centre chirurgical Marie Lannelongue, Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), and HAL UPMC, Gestionnaire
Subjects: Serum, 0301 basic medicine, [SDV]Life Sciences [q-bio], MyoD, 0302 clinical medicine, Myosin, Myocyte, Receptors, Cholinergic, Functional ability, Cells, Cultured, Myogenesis, Experimental autoimmune myasthenia gravis (EAMG), Antibodies, Monoclonal, Cell Differentiation, Middle Aged, AChR antibodies, medicine.anatomical_structure, Female, Myogenin, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], tissues, Adult, medicine.medical_specialty, Satellite Cells, Skeletal Muscle, Biology, Pathology and Forensic Medicine, Young Adult, 03 medical and health sciences, Cellular and Molecular Neuroscience, Cardiotoxin, Internal medicine, Myasthenia Gravis, medicine, Animals, Humans, Regeneration, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], RNA, Messenger, Myogenic factors, Muscle, Skeletal, Cell Proliferation, Cell Size, Skeletal muscle, medicine.disease, Myasthenia gravis, Myasthenia Gravis, Autoimmune, Experimental, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, Endocrinology, Neurology (clinical), 030217 neurology & neurosurgery, MG patients
Abstract: International audience; Myasthenia gravis (MG) is a neuromuscular disease caused in most cases by anti-acetyl-choline receptor (AChR) autoantibodies that impair neuromuscular signal transmission and affect skeletal muscle homeostasis. Myogenesis is carried out by muscle stem cells called satellite cells (SCs). However, myogenesis in MG had never been explored. The aim of this study was to characterise the functional properties of myasthenic SCs as well as their abilities in muscle regeneration. SCs were isolated from muscle biopsies of MG patients and age-matched controls. We first showed that the number of Pax7+ SCs was increased in muscle sections from MG and its experimental autoimmune myasthenia gravis (EAMG) mouse model. Myoblasts isolated from MG muscles proliferate and differentiate more actively than myoblasts from control muscles. MyoD and MyoG were expressed at a higher level in MG myoblasts as well as in MG muscle biopsies compared to controls. We found that treatment of control myoblasts with MG sera or monoclonal anti-AChR antibodies increased the differentiation and MyoG mRNA expression compared to control sera. To investigate the functional ability of SCs from MG muscle to regenerate, we induced muscle regeneration using acute cardiotoxin injury in the EAMG mouse model. We observed a delay in maturation evidenced by a decrease in fibre size and MyoG mRNA expression as well as an increase in fibre number and embryonic myosin heavy-chain mRNA expression. These findings demonstrate for the first time the altered function of SCs from MG compared to control muscles. These alterations could be due to the anti-AChR antibodies via the modulation of myogenic markers resulting in muscle regeneration impairment. In conclusion, the autoimmune attack in MG appears to have unsuspected pathogenic effects on SCs and muscle regeneration, with potential consequences on myogenic signalling pathways, and subsequently on clinical outcome, especially in the case of muscle stress.
Published: 2017

44. Optical study of using ceramic foams for volumetric solar receivers

Author: Mohamed A. A. Attia, Mohamed Rady, Emad M.M. Ewais, Mahmoud Alaa, Laboratoire de Mécanique Gabriel Lamé (LaMé), Université d'Orléans (UO)-Institut National des Sciences Appliquées - Centre Val de Loire (INSA CVL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Tours (UT), Université d'Helwan, Helwan University [Caire], Central Metallurgical Research and Development Institute (CMRDI), European Project: 608593,EC:FP7:ENERGY,FP7-ENERGY-2013-1,EUROSUNMED(2013), Université d'Orléans (UO)-Université de Tours-Institut National des Sciences Appliquées - Centre Val de Loire (INSA CVL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA), Transferts, écoulements, fluides, énergétique (TREFLE), Université Sciences et Technologies - Bordeaux 1-École Nationale Supérieure de Chimie et de Physique de Bordeaux (ENSCPB)-Centre National de la Recherche Scientifique (CNRS), Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), and Université d'Orléans (UO)-Université de Tours (UT)-Institut National des Sciences Appliquées - Centre Val de Loire (INSA CVL)
Subjects: Materials science, Optical simulation, 020209 energy, Volumetrie solar receiver, 02 engineering and technology, 7. Clean energy, [SPI]Engineering Sciences [physics], Optics, Thermal, Concentrated solar power, component, 0202 electrical engineering, electronic engineering, information engineering, Solar radiation, Solar ray tracing, Ceramic, Porosity, Penetration depth, Monte Carlo, Optical efficiency, Solar furnace, business.industry, Molar absorptivity, [SPI.MECA.GEME]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Mechanical engineering [physics.class-ph], Heat flux, visual_art, visual_art.visual_art_medium, [SPI.MECA.THER]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Thermics [physics.class-ph], business
Abstract: International audience; Ceramic foams are promising materials for volumetric solar receivers in concentrated solar power (CSP) plants. Understanding the solar heat flux distribution on the receiver is of great importance for optimizing the receiver volumetric efficiency and thermal performance. This work presents a 3D optical analysis of ceramic based volumetric solar receivers. The optical analysis is conducted using a Monte Carlo based solar ray tracing software. Ceramic foams are represented by idealized packed tetrakaidecahedron structures. The absorbed heat flux distribution and the effect of cell size, porosity and absorptivity on the penetration depth of the absorbed heat flux are investigated. Comparisons have been made with extruded honeycomb receivers. The results clearly demonstrate the dependence of flux distribution and penetration depth of solar rays on the material absorptivity and structure. The simulation results show a uniform heat flux distribution on the frontal faces with an intensity that increases with increasing the material absorptivity. Both the porosity and the cell size have a great effect on the penetration depth of the absorbed heat flux. In general, foam structure shows larger penetration depths than extruded honeycombs.
Published: 2017

45. Evidence for Novel Action at the Cell-Binding Site of Human Angiogenin Revealed by Heteronuclear NMR Spectroscopy, in silico and in vivo Studies

Author: José Courty, Josette Badet, Dimitri Komiotis, Aikaterini C. Tsika, Vassiliki T. Skamnaki, Joseph Hayes, Vanessa Parmenopoulou, Demetra S.M. Chatzileontiadou, Zoi Diamantopoulou, Georgios A. Spyroulias, Jean Delbé, Demetres D. Leonidas, Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Développement humain : Croissance et différenciation, Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire CRRET, EAC/CNRS-7149, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Department of Pharmacy, University of Patras [Greece], Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-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 de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-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), and University of Patras [Patras]
Subjects: 0301 basic medicine, Angiogenin, RNase P, [SDV]Life Sciences [q-bio], Neovascularization, Physiologic, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Chick Embryo, Molecular Dynamics Simulation, Biochemistry, Chorioallantoic Membrane, Cell Line, 03 medical and health sciences, Structure-Activity Relationship, 0302 clinical medicine, In vivo, Drug Discovery, Animals, Humans, Computer Simulation, General Pharmacology, Toxicology and Pharmaceutics, Nuclear Magnetic Resonance, Biomolecular, ComputingMilieux_MISCELLANEOUS, Pharmacology, Binding Sites, biology, Chemistry, Organic Chemistry, Active site, Nucleoside inhibitor, Nuclear magnetic resonance spectroscopy, Ribonuclease, Pancreatic, Pyrimidine Nucleosides, 3. Good health, 030104 developmental biology, Heteronuclear molecule, Docking (molecular), 030220 oncology & carcinogenesis, biology.protein, Biophysics, Molecular Medicine
Abstract: A member of the ribonuclease A superfamily, human angiogenin (hAng) is a potent angiogenic factor. Heteronuclear NMR spectroscopy combined with induced-fit docking revealed a dual binding mode for the most antiangiogenic compound of a series of ribofuranosyl pyrimidine nucleosides that strongly inhibit hAng's angiogenic activity in vivo. While modeling suggests the potential for simultaneous binding of the inhibitors at the active and cell-binding sites, NMR studies indicate greater affinity for the cell-binding site than for the active site. Additionally, molecular dynamics simulations at 100 ns confirmed the stability of binding at the cell-binding site with the predicted protein-ligand interactions, in excellent agreement with the NMR data. This is the first time that a nucleoside inhibitor is reported to completely inhibit the angiogenic activity of hAng in vivo by exerting dual inhibitory activity on hAng, blocking both the entrance of hAng into the cell and its ribonucleolytic activity.
Published: 2017

46. Pleiotrophin Exerts Its Migration and Invasion Effect through the Neuropilin-1 Pathway

Author: Yamina Hamma-Kourbali, Charly Blanc, Sophie Frechault, Ilaria Cascone, Gilles Carpentier, Damien Destouches, José Courty, Jean Delbé, Rania Elahouel, Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Laboratoire CRRET, EAC/CNRS-7149, and Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: Cancer Research, Angiogenesis, Recombinant Fusion Proteins, medicine.medical_treatment, Immunoblotting, CHO Cells, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, Pleiotrophin, lcsh:RC254-282, Article, Focal adhesion, Cricetulus, Cell Movement, Cell Line, Tumor, Cricetinae, [SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB], Neuropilin 1, medicine, Animals, Humans, Neoplasm Invasiveness, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, Glutathione Transferase, Binding Sites, Growth factor, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Endocytosis, Neuropilin-1, 3. Good health, Cell biology, Microscopy, Fluorescence, Tumor progression, Cancer research, Cytokines, RNA Interference, Human umbilical vein endothelial cell, Signal transduction, Carrier Proteins, Protein Binding, Signal Transduction
Abstract: Pleiotrophin (PTN) is a pleiotropic growth factor that exhibits angiogenic properties and is involved in tumor growth and metastasis. Although it has been shown that PTN is expressed in tumor cells, few studies have investigated its receptors and their involvement in cell migration and invasion. Neuropilin-1 (NRP-1) is a receptor for multiple growth factors that mediates cell motility and plays an important role in angiogenesis and tumor progression. Here we provide evidence for the first time that NRP-1 is crucial for biological activities of PTN. We found that PTN interacted directly with NRP-1 through its thrombospondin type-I repeat domains. Importantly, binding of PTN to NRP-1 stimulated the internalization and recycling of NRP-1 at the cell surface. Invalidation of NRP-1 by RNA interference in human carcinoma cells inhibited PTN-induced intracellular signaling of the serine-threonine kinase, mitogen-activated protein MAP kinase, and focal adhesion kinase pathways. Accordingly, NRP-1 silencing or blocking by antibody inhibited PTN-induced human umbilical vein endothelial cell migration and tumor cell invasion. These results suggest that NRP-1/PTN interaction provides a novel mechanism for controlling the response of endothelial and tumoral cells to PTN and may explain, at least in part, how PTN contributes to tumor angiogenesis and cancer progression.
Published: 2015

47. N6L pseudopeptide interferes with nucleophosmin protein-protein interactions and sensitizes leukemic cells to chemotherapy

Author: A. Di Matteo, Luca Federici, Ilaria Cascone, Rodolfo Ippoliti, E. Clemente, Maria Angela Franceschini, Annamaria Cimini, Damien Destouches, R. Celani, Anne Chloe Dhez, F. Raineri, Benoit Vallée, José Courty, Gianni Colotti, V De Laurenzi, A De Cola, STMicroelectronics, Department of Health, Life and Environmental Sciences, Università degli Studi dell'Aquila (UNIVAQ), Laboratoire de photonique et de nanostructures (LPN), Centre National de la Recherche Scientifique (CNRS), Department of Experimental Medicine and Biochemical Sciences, IDI,IRCCS, Biochemistry Laboratory, Università degli Studi di Roma Tor Vergata [Roma], Laboratoire CRRET, EAC/CNRS-7149, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Service de médecine interne diabète et maladies métaboliqe, Hôpital civil Strasbourg, and Università degli Studi dell'Aquila = University of L'Aquila (UNIVAQ)
Subjects: 0301 basic medicine, Cancer Research, NPM1, DNA damage, [SDV]Life Sciences [q-bio], [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Targeted therapy, 03 medical and health sciences, Cell Line, Tumor, medicine, Humans, ComputingMilieux_MISCELLANEOUS, Nucleophosmin, Acute myeloid leukemia, Cell growth, RUNX1T1, Cytarabine, Myeloid leukemia, Nuclear Proteins, NPM1 mutations, 3. Good health, Leukemia, Myeloid, Acute, 030104 developmental biology, Oncology, Doxorubicin, Mutation, Cancer research, Tumor Suppressor Protein p53, Peptides, Nucleolin, medicine.drug
Abstract: NPM1 is a multifunctional nucleolar protein implicated in several processes such as ribosome maturation and export, DNA damage response and apoptotic response to stress stimuli. The NPM1 gene is involved in human tumorigenesis and is found mutated in one third of acute myeloid leukemia patients, leading to the aberrant cytoplasmic localization of NPM1. Recent studies indicated that the N6L multivalent pseudopeptide, a synthetic ligand of cell-surface nucleolin, is also able to bind NPM1 with high affinity. N6L inhibits cell growth with different mechanisms and represents a good candidate as a novel anticancer drug for a number of malignancies of different histological origin. In this study we investigated whether N6L treatment could drive antitumor effect in acute myeloid leukemia cell lines. We found that N6L binds NPM1 at the N-terminal domain, co-localizes with cytoplasmic, mutated NPM1, and interferes with its protein-protein associations. N6L toxicity appears to be p53 dependent but interestingly, the leukemic cell line harbouring the mutated form of NPM1 is more resistant to treatment, suggesting that NPM1 cytoplasmic delocalization confers protection from p53 activation. Moreover, we show that N6L sensitizes AML cells to doxorubicin and cytarabine treatment. These studies suggest that N6L may be a promising option in combination therapies for acute myeloid leukemia treatment.
Published: 2017

48. Repurposing doxycycline for synucleinopathies: remodelling of α-synuclein oligomers towards non-toxic parallel beta-sheet structured species

Author: Claudio O. Fernández, Rosangela Itri, Julia E. Sepulveda-Diaz, Sergio B. Socías, Rosana Chehín, Rita Raisman-Vozari, Florencia González-Lizárraga, Leandro R.S. Barbosa, Dulce Papy-Garcia, Clarisa M. Torres-Bugeau, César Ávila, Elaine Del-Bel, Andres Binolfi, Universidad Nacional de Tucumán (UNT), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), University of São Paulo (IFUSP), Max Planck Laboratory for Structural Biology, Chemistry and Molecular Biophysics of Rosario (MPLbioR), Universidad Nacional de Rosario [Santa Fe]-Max Planck Institute for Biophysical Chemistry (MPI-BPC), Max-Planck-Gesellschaft-Max-Planck-Gesellschaft, Universidade de São Paulo (USP), Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-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)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Universidade de São Paulo = University of São Paulo (USP), and HAL UPMC, Gestionnaire
Subjects: Models, Molecular, 0301 basic medicine, Amyloid, Magnetic Resonance Spectroscopy, Cell Survival, Otras Ciencias Biológicas, [SDV]Life Sciences [q-bio], Biology, Protein aggregation, Pharmacology, Protein Aggregation, Pathological, Neuroprotection, Article, Ciencias Biológicas, purl.org/becyt/ford/1 [https], Protein Aggregates, 03 medical and health sciences, 0302 clinical medicine, Cell Line, Tumor, Spectroscopy, Fourier Transform Infrared, medicine, Humans, purl.org/becyt/ford/1.6 [https], Neuroinflammation, Repurposing, Inhibition, Synuclein, Synucleinopathies, Multidisciplinary, Neurodegeneration, Drug Repositioning, Neurodegenerative Diseases, medicine.disease, 3. Good health, Cell biology, [SDV] Life Sciences [q-bio], 030104 developmental biology, Doxycycline, alpha-Synuclein, Protein Conformation, beta-Strand, Protein Multimerization, CIENCIAS NATURALES Y EXACTAS, 030217 neurology & neurosurgery, Protein Binding
Abstract: Synucleinophaties are progressive neurodegenerative disorders with no cure to date. An attractive strategy to tackle this problem is repurposing already tested safe drugs against novel targets. In this way, doxycycline prevents neurodegeneration in Parkinson models by modulating neuroinflammation. However, anti-inflammatory therapy per se is insufficient to account for neuroprotection. Herein we characterise novel targets of doxycycline describing the structural background supporting its effectiveness as a neuroprotector at subantibiotic doses. Our results show that doxycycline reshapes α-synuclein oligomers into off-pathway, high-molecular-weight species that do not evolve into fibrils. Off-pathway species present less hydrophobic surface than on-pathway oligomers and display different β-sheet structural arrangement. These structural changes affect the α-synuclein ability to destabilize biological membranes, cell viability, and formation of additional toxic species. Altogether, these mechanisms could act synergically giving novel targets for repurposing this drug. Fil: González Lizarraga, Maria Florencia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina. Universite Pierre et Marie Curie; Francia. Centre de Recherche de I'Institut du Cerveau et de la Moelle Epinière; Francia Fil: Socias, Sergio Benjamin. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina Fil: Avila, Cesar Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina Fil: Torres Bugeau, Clarisa Maria. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina Fil: Barbosa, Leandro R. S.. Universidade de Sao Paulo; Brasil Fil: Binolfi, Andrés. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; Argentina Fil: Sepúlveda Díaz, Julia E.. Centre de Recherche de I'Institut du Cerveau et de la Moelle Epinière; Francia. Universite Pierre et Marie Curie; Francia Fil: Del Bel, Elaine. Universidade de Sao Paulo; Brasil Fil: Fernandez, Claudio Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario. Universidad Nacional de Rosario. Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario; Argentina Fil: Garcia Orozco Ep Papy, Dulce Maria. Centre National de la Recherche Scientifique; Francia. Université Paris-Est Créteil; Francia Fil: Itri, Rosangela. Universidade de Sao Paulo; Brasil Fil: Raisman Vozari, Rita. Centre National de la Recherche Scientifique; Francia. Centre de Recherche de I'Institut du Cerveau et de la Moelle Epinière; Francia. Universite Pierre et Marie Curie; Francia Fil: Chehin, Rosana Nieves. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tucumán. Instituto Superior de Investigaciones Biológicas. Universidad Nacional de Tucumán. Instituto Superior de Investigaciones Biológicas; Argentina
Published: 2017

49. Cell Colonization Ability of a Commercialized Large Porous Alveolar Scaffold

Author: José Courty, Nathalie Chevallier, Thibault Lemaire, Hélène Rouard, Thibault Bouderlique, S. Lemonnier, Salah Naili, Patricia Albanese, Laboratoire de Modélisation et Simulation Multi Echelle (MSME), Centre National de la Recherche Scientifique (CNRS)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Université Paris-Est Marne-la-Vallée (UPEM), Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Unité d’Ingénierie et de thérapie cellulaire, Etablissement Français du Sang, Biomécanique cellulaire et respiratoire (BCR), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), EAC 7149, Laboratoire de Modélisation et Simulation Multi Echelle ( MSME ), Université Paris-Est Marne-la-Vallée ( UPEM ) -Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de recherche sur la croissance cellulaire, la réparation et la régénération tissulaires ( CRRET ), Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ) -Centre National de la Recherche Scientifique ( CNRS ), Biomécanique cellulaire et respiratoire ( BCR ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ) -Centre National de la Recherche Scientifique ( CNRS ), and Université Paris-Est Marne-la-Vallée (UPEM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Scaffold, Article Subject, QH301-705.5, 0206 medical engineering, Cell, Biomedical Engineering, Medicine (miscellaneous), Bioengineering, 02 engineering and technology, In vivo, medicine, Biology (General), Porosity, ComputingMilieux_MISCELLANEOUS, Chemistry, Mesenchymal stem cell, [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], 021001 nanoscience & nanotechnology, Biocompatible material, 020601 biomedical engineering, Porous scaffold, medicine.anatomical_structure, Biophysics, Seeding, [ SPI.MECA.BIOM ] Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], 0210 nano-technology, TP248.13-248.65, Research Article, Biotechnology
Abstract: The use of filling biomaterials or tissue-engineered large bone implant-coupling biocompatible materials and human bone marrow mesenchymal stromal cells seems to be a promising approach to treat critical-sized bone defects. However, the cellular seeding onto and into large porous scaffolds still remains challenging since this process highly depends on the porous microstructure. Indeed, the cells may mainly colonize the periphery of the scaffold, leaving its volume almost free of cells. In this study, we carry out an in vitro study to analyze the ability of a commercialized scaffold to be in vivo colonized by cells. We investigate the influence of various physical parameters on the seeding efficiency of a perfusion seeding protocol using large manufactured bone substitutes. The present study shows that the velocity of the perfusion fluid and the initial cell density seem to impact the seeding results and to have a negative effect on the cellular viability, whereas the duration of the fluid perfusion and the nature of the flow (steady versus pulsed) did not show any influence on either the fraction of seeded cells or the cellular viability rate. However, the cellular repartition after seeding remains highly heterogeneous.
Published: 2017

50. Heparan sulfates and the decrease of N-glycans promote early adipogenic differentiation rather than myogenesis of murine myogenic progenitor cells

Author: Paul-François Gallet, Anne Da Silva, Sandrine Chantepie, Dulce Papy-Garcia, Abderrahman Maftah, Vincent Grassot, Amel Bouchatal, Jean-Michel Petit, Unité de Génétique Moléculaire Animale (UMR GMA), Institut National de la Recherche Agronomique (INRA)-Université de Limoges (UNILIM), Génomique AniMale, Amélioration, Adaptation (GAMAA), Institut National de la Recherche Agronomique (INRA)-PEIRENE (PEIRENE), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Croissance cellulaire, réparation et régénération tissulaires (CRRET), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Université de Limoges (UNILIM)-Institut National de la Recherche Agronomique (INRA), EAC 7149, Centre National de la Recherche Scientifique (CNRS), Laboratoire Croissance Régéneration Réparatrice et Régéneration Tissu, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Region Limousin, University of Limoges, INRA, and Unité de Génétique Moléculaire Animale (UGMA)
Subjects: 0301 basic medicine, Cancer Research, N-glycan sialylation, Glycosylation, murine myogenic progenitor cells (MPC), Cellular differentiation, [SDV]Life Sciences [q-bio], Muscle Fibers, Skeletal, Biology, Muscle Development, Transcriptome, Mice, 03 medical and health sciences, chemistry.chemical_compound, Polysaccharides, cellule satellite, satellite cell, Adipocytes, Animals, Myocyte, acide sialique, Progenitor cell, glycosylation related genes, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Muscle Cells, Adipogenesis, Myogenesis, facteur environnemental, Stem Cells, Cell Differentiation, in vitro, Cell Biology, myogénèse, Cell biology, étude transcriptomique, carbohydrates (lipids), n glycan, heparane sulfate, 030104 developmental biology, Biochemistry, chemistry, sialic acid, early adipogenesis, myogenesis Heparan sulfates, Stem cell, Developmental Biology, heparitin sulfate
Abstract: In vitro, extracted muscle satellite cells, called myogenic progenitor cells, can differentiate either in myotubes or preadipocytes, depending on environmental factors and the medium. Transcriptomic analyses on glycosylation genes during satellite cells differentiation into myotubes showed that 31 genes present a significant variation of expression at the early stages of murine myogenic progenitor cells (MPC) differentiation. In the present study, we analyzed the expression of 383 glycosylation related genes during murine MPC differentiation into preadipocytes and compared the data to those previously obtained during their differentiation into myotubes. Fifty-six glycosylation related genes are specifically modified in their expression during early adipogenesis. The variations correspond mainly to: a decrease of N-glycans, and of alpha (2,3) and (2,6) linked sialic acids, and to a high level of heparan sulfates. A high amount of TGF-beta 1 in extracellular media during early adipogenesis was also observed. It seems that the increases of heparan sulfates and TGF-beta 1 favor pre-adipogenic differentition of MPC and possibly prevent their myogenic differentiation.
Published: 2017

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