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1. Inhalation incidents and respiratory health: results from the European Community respiratory health survey

Author: Mirabelli, Mc, Olivieri, Mario, Kromhout, H, Norbäck, D, Radon, K, Torén, K, van Sprundel, M, Villani, S, Zock, Jp, European Community Respiratory Health Survey, Risk Assessment of Toxic and Immunomodulatory Agents, and Dep IRAS
Subjects: Adult, Male, medicine.medical_specialty, respiratory health, Respiratory Mucosa, Article, Occupational medicine, Young Adult, Epidemiology, medicine, Humans, Longitudinal Studies, Respiratory sounds, Intensive care medicine, Respiratory Sounds, Asthma, Inhalation exposure, inhalation, Inhalation Exposure, Inhalation, medicine.diagnostic_test, business.industry, Respiratory disease, Public Health, Environmental and Occupational Health, accident, Middle Aged, medicine.disease, Health Surveys, respiratory tract diseases, Europe, Cough, Bronchial hyperresponsiveness, asthma, epidemiology, Emergency medicine, Female, Human medicine, Bronchial Hyperreactivity, business
Abstract: Background Inhalation incidents are an important cause of acute respiratory symptoms, but little is known about how these incidents affect chronic respiratory health. Methods We assessed reported inhalation incidents among 3,763 European Community Respiratory Health Survey (ECRHS) participants with and without cough, phlegm, asthma, wheezing or bronchial hyperresponsiveness. We then examined whether inhalation incidents during the 9-year ECRHS follow-up period were associated with a new onset of any of these respiratory outcomes among 2,809 participants who were free of all five outcomes at the time of the baseline ECRHS survey. Results Inhalation incidents were reported by 5% of participants, with higher percentages reported among individuals with asthma-related outcomes at the time of the baseline survey. Among participants without symptoms at baseline, our analyses generated non-statistically significant elevated estimates of the risk of cough, phlegm, asthma and wheezing and a non-statistically significant inverse estimate of the risk of bronchial hyperresponsiveness among participants who reported an inhalation incident compared to those without such an event reported. Discussion Our findings provide limited evidence of an association between inhalation incidents and asthma-related symptoms. These data could be affected by differences in the reporting of inhalation incidents according to symptom status at the time of the baseline survey; they should thus be interpreted with caution.
Published: 2009
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2. Do asthma and allergy influence subsequent pet keeping? An analysis of childhood and adulthood

Author: Svanes, C., Zock, J.P., Antò, J.M., Dharmage, S., Norbäck, D., Wjst, M., Heinrich, J., Jarvis, D., de Marco, R., Plana, E., Raherison, C., Sunyer, J., and European Community Respiratory Health Survey II ()
Subjects: Adult, Pediatrics, medicine.medical_specialty, Allergy, Adolescent, Immunology, Disease, Birds, Atopy, Dogs, medicine, Animals, Humans, Immunology and Allergy, Longitudinal Studies, Child, Asthma, selective avoidance, pets, cats, dogs, birds, asthma, atopy, ECRHS, business.industry, Respiratory disease, Age Factors, Infant, Newborn, Infant, Odds ratio, Allergens, Middle Aged, medicine.disease, Europe, El Niño, Animals, Domestic, Child, Preschool, Cats, Hay fever, business, Follow-Up Studies
Abstract: Background: Asthma and allergy might influence the choice of keeping pets, leading to apparent protective effects of pets on allergic disease. Objective: We investigated the effects of asthma and allergy on subsequent pet keeping in childhood and adulthood. Methods: Information about asthma and pet keeping at ages 0 to 4, 5 to 15, 20 to 44, and 26 to 56 years was provided by 9812 subjects participating in the 9-year follow-up of the European Community Respiratory Health Survey. Results: In childhood asthma debut at younger than 5 years was associated with less cat keeping at 5 to 15 years (odds ratio [OR], 0.60; 95% CI, 0.44-0.82), an effect only observed when the parents did not have asthma or allergy (P interaction = .045). Childhood asthma did not influence adult pet ownership, unless there were adult symptoms. Adults less often acquired cats at follow-up if they had 3 or more asthma symptoms (OR, 0.78; 95% CI, 0.64-0.95), were taking asthma medication (OR, 0.48; 95% CI, 0.31-0.74), had hay fever (OR, 0.75; 95% CI, 0.62-0.91), had atopy (OR, 0.75; 95% CI, 0.61-0.91), or had specific IgE to cat (OR, 0.57; 95% CI, 0.39-0.82) at baseline. Adults who already had pets usually continued keeping the same type of pet, except that the presence of 3 or more asthma symptoms was associated with less subsequent dog keeping (OR, 0.69; 95% CI, 0.53-0.89). Pet removal between surveys to reduce allergen was reported by 4.7%. Conclusion: Selective avoidance subsequent to asthma or allergy was observed for childhood cat keeping and adult cat acquisition. Avoidance would produce an apparent protective effect of cats on childhood asthma (large OR, 0.83). Avoidance was generally not observed for dogs or birds. Clinical implications: A part of the protective effects of childhood cats on asthma and allergy can be attributed to selective avoidance. © 2006 American Academy of Allergy, Asthma and Immunology.
Published: 2006
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3. The socio-economic burden of asthma is substantial in Europe

Author: Accordini, S, Corsico, A, Cerveri, I, Gislason, D, Gulsvik, A, Janson, C, Jarvis, D, Marcon, A, Pin, I, Vermeire, P, Almar, E, Bugiani, M, Cazzoletti, L, Duran-Tauleria, E, Jõgi, R, Marinoni, A, Martínez-Moratalla, J, Leynaert, B, de Marco, R, Therapy and Health Economics Working Group of the European Community Respiratory Health Survey II, Vesin, Aurélien, Department of Diagnostics and Public Health [Verona] (UNIVR | DDSP), Università degli studi di Verona = University of Verona (UNIVR), Division of Respiratory Diseases, Università degli Studi di Pavia = University of Pavia (UNIPV)-San Matteo Hospital, Department of Allergy, Respiratory Medicine and Sleep, Landspitali University Hospital, Department of Thoracic Medicine [Bergen], Haukeland University Hospital, University of Bergen (UiB)-University of Bergen (UiB), Department of Medical Sciences, Respiratory Medicine & Allergology, Uppsala University, Respiratory Epidemiology and Public Health Group, Imperial College London-National Heart and Lung Institute [UK], Groupe de Recherche Sur Le Cancer du Poumon : Bases Moléculaires de la Progression Tumorale, Dépistage et Thérapie Génique, Institut Albert Bonniot-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut d'oncologie/développement Albert Bonniot de Grenoble (INSERM U823), Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Campus Drie Eiken, University of Antwerp (UA), Unit of Epidemiology, Public Health Department of Castilla La Mancha, Unit of Pneumology, Consorzio Provinciale Antitubercolare, IMIM-Hospital del Mar, Generalitat de Catalunya, Foundation Tartu University Clinics, Lung Clinic, Department of Applied Health Sciences, Università degli Studi di Pavia = University of Pavia (UNIPV), Servicio de Neumología, Complejo Hospitalario Universitario de Albacete-Servicio de Salud de Castilla-La Mancha, Physiopathologie et Epidemiologie de l'Insuffisance Respiratoire, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Verona (UNIVR), University of Pavia-San Matteo Hospital, Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS-CHU Grenoble-Université Joseph Fourier - Grenoble 1 (UJF), and University of Pavia
Subjects: Adult, Male, MESH: Socioeconomic Factors, MESH: Health Expenditures, MESH: Asthma, MESH: Probability, MESH: Logistic Models, ECRHS, MESH: Risk Assessment, Risk Assessment, MESH: Multivariate Analysis, MESH: Cross-Sectional Studies, Cost of Illness, Sickness Impact Profile, Humans, Probability, MESH: Middle Aged, MESH: Humans, MESH: Health Services, socio-economic burden, asthma, Europe, population-based study, ECRHS, MESH: Quality of Life, MESH: Adult, Health Services, Middle Aged, MESH: Cost of Illness, Asthma, MESH: Male, Europe, Cross-Sectional Studies, Logistic Models, MESH: Sickness Impact Profile, Socioeconomic Factors, socio-economic burden, population-based study, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Multivariate Analysis, Quality of Life, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Europe, Health Expenditures, MESH: Female
Abstract: International audience; BACKGROUND: Few data are available on the asthma burden in the general population. We evaluated the level and the factors associated with the asthma burden in Europe. METHODS: In 1999-2002, 1152 adult asthmatics were identified in the European Community Respiratory Health Survey (ECRHS)-II and the socio-economic burden (reduced activity days and hospital services utilization in the past 12 months) was assessed. RESULTS: The asthmatics with a light burden (only a few reduced activity days) were 13.2% (95% CI: 11.4-15.3%), whereas those with a heavy burden (many reduced activity days and/or hospital services utilization) were 14.0% (95% CI: 12.1-16.1%). The burden was strongly associated with disease severity and a lower quality of life. Obese asthmatics had a significantly increased risk of a light [relative risk ratio (RRR) = 2.17; 95% CI: 1.18-4.00] or a heavy burden (RRR = 2.77; 95% CI: 1.52-5.05) compared with normal/underweight subjects. The asthmatics with frequent respiratory symptoms showed a threefold (RRR = 2.74; 95% CI: 1.63-4.61) and sixfold (RRR = 5.76; 95% CI: 3.25-10.20) increased risk of a light or a heavy burden compared with asymptomatic asthmatics, respectively. Moreover, the lower the forced expiratory volume in 1 s % predicted, the higher the risk of a heavy burden. The coexistence with chronic cough/phlegm only increased the risk of a heavy burden (RRR = 1.88; 95% CI: 1.16-3.06). An interaction was found between gender and IgE sensitization, with nonatopic asthmatic females showing the highest risk of a heavy burden (21.6%; 95% CI: 16.9-27.1%). CONCLUSIONS: The asthma burden is substantial in Europe. A heavy burden is more common in asthmatics with obesity, frequent respiratory symptoms, low lung function, chronic cough/phlegm and in nonatopic females.
Published: 2008
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4. Asthma characteristics in cleaning workers, workers in other risk jobs and office workers

Author: Zock, J. P., Kogevinas, M., Sunyer, J., Jarvis, D., Tore´, K., Anto´, J. M., Z, Abramson, for the European Community Respiratory Health Survey Australia: M., Kutin, J., Belgium: P. Vermeire, F. van Bastelaer, Germany: H. Magnussen, D. Nowak, H. E. Wichmann, J. Heinrich, Gislason, Iceland: T. Gislason D., Prichard, Ireland: J., Allwright, S., Macleod, D., Bugiani, Italy: M., Bucca, Caterina, Romano, C., de Marco lo Cascio, R., Campello, C., Marinoni, A., Cerveri, I., Casali, L., Perfetti, L., Rijcken, The Netherlands: B., Schouten, J. P., Kerkhof, M., Boezen, H. M., Crane, New Zealand: J., Lewis, S., Pearce, N., Norway: A. Gulsvik, E. Omenaas, Anto´, Spain: J. M., Soriano, J., Tobı´as, A., Roca, J., Muniozguren, N., Ramos Gonza´ lez, J., Capelastegui, A., Martı´nez Moratalla, J., Maldonado Pe´rez, E. Almar J., Pereira, A., Sa´nchez, J., Quiro´s, J., Huerta, I., Boman, Sweden: G., Janson, C., Bjo¨ rnsson, E., Rosenhall, L., Lundba¨ck, E. Norrman B., Lindholm, N., Plaschke, P., Tore´n, K., Ku¨nzli, Switzerland: N., Hall, United Kingdom: R., Harrison, B., Stark, J., Buist, USA: S., Vollmer, W., The following grants helped to fund the local studies: Australia: Allen, M. O. s. b. o. r. n. e., H. a. n. b. u. r. y. 9. s. Belgium: Belgian Science Policy Office, National Fund for Scientific R. e. s. e. a. r. c. h. Germany: GSF, Forschung und Technologie, the Bundesminister fu¨ r., Tecnologica, B. o. n. n. Italy: Ministero dell9Universita e. della Ricerca Scientifica e., Cnr, and Regione Veneto grant RSF, n. 3. 8. 1. /. 0. 5. 9. 3.
Subjects: Adult, Male, Pulmonary and Respiratory Medicine, Chronic bronchitis, medicine.medical_specialty, SYMPTOMS, Vital Capacity, Population, cleaning, Peak Expiratory Flow Rate, RESPIRATORY-HEALTH-SURVEY, Bronchial Provocation Tests, DISEASE, Atopy, asthma risk cleaning workers, Risk Factors, Forced Expiratory Volume, Occupational Exposure, Surveys and Questionnaires, Environmental health, occupation, Humans, Medicine, EXPOSURE, Occupations, Risk factor, education, OCCUPATIONAL ASTHMA, POPULATION, Asthma, education.field_of_study, business.industry, VALUES, Absolute risk reduction, Immunoglobulin E, asthma, medicine.disease, respiratory tract diseases, Occupational Diseases, Bronchial hyperresponsiveness, CLEANERS, Physical therapy, Female, European Community Respiratory Health Survey, SENSITIVITY, business, Occupational asthma
Abstract: Several studies have demonstrated an excess risk for asthma among cleaning workers. The aim of this analysis was to compare clinical, immunological and functional characteristics associated with asthma in cleaners and other occupational groups.Cleaners, workers exposed to high molecular weight (MW) agents, workers exposed to low MW agents, and office workers were identified from an international community-based epidemiological study. Influence of sex, smoking, age and atopy on the relationships with asthma was investigated. Rates of respiratory symptoms, bronchial hyperresponsiveness, atopic sensitisation and lung function were compared between asthmatics from the four groups (case-case analysis).The risk for asthma in workers exposed to low MW agents was higher among nonatopics than among atopics. Case-case analysis showed no major differences in asthma characteristics between cleaners and workers exposed to high or low MW agents. Asthmatic cleaners had less atopy, more chronic bronchitis and a lower lung function as compared to office workers.Asthma in cleaning workers showed many similarities with that in workers known to be at risk for occupational asthma. Atopic sensitisation did not seem to play an important role in cleaning-related asthma.
Published: 2002

5. The distribution of total and specific serum IgE in the European Community Respiratory Health Survey

Author: Burney, P, Malmberg, E, Chinn, S, Jarvis, D, Luczynska, C, Lai, E, DE MARCO, Roberto, LO CASCIO, Vincenzo, Campello, Cesare, and European Community Respiratory Health Survey
Subjects: Allergy, grass, birch, Dermatophagoides pteronyssinus, Immunology, cat, Immunoglobulin E, medicine.disease_cause, Serology, Atopy, Allergen, Seroepidemiologic Studies, Surveys and Questionnaires, Hypersensitivity, Prevalence, Immunology and Allergy, Medicine, Animals, Humans, ragweed, Asthma, Cladosporium herbarum, House dust mite, Serum IgE, Mites, biology, business.industry, Australia, Aeroallergen, Dust, Allergens, medicine.disease, biology.organism_classification, Parietaria judaica, United States, Europe, biology.protein, Cats, Pollen, business, prevalence, Cladosporium, New Zealand
Abstract: Background: Variations in the prevalence of atopy could provide important clues to the etiology of atopy and asthma. Although estimates of prevalence are available from different studies, a lack of standardization makes comparisons difficult. Objective: This study was conducted to estimate the variation of geometric mean levels of serum IgE and the prevalence of specific IgE to common allergens between populations as part of the European Community Respiratory Health Survey (ECRHS), a multicenter survey of asthma and risk factors for asthma. Methods: Random samples of subjects living in 37 centers in 16 countries who had answered a questionnaire about their respiratory symptoms were invited for further assessment including total serum IgE and the presence of specific IgE against house dust mite (Dermatophagoides pteronyssinus) , timothy grass, cat, Cladosporium herbarum, and a local allergen. Sera were tested from 13,883 persons. Results: The estimated prevalence of atopy, defined as the presence of at least one positive specific IgE, ranged from 16% in Albacete (Spain) to 45% in Christchurch (New Zealand). The geometric mean total serum IgE varied from 13 kU/L in Reykjavik (Iceland) to 62 kU/L in Bordeaux (France). There was no relation between the geometric mean total serum IgE in a center and the prevalence of atopy. Conclusions: There are substantial variations in the prevalence of atopy and the level of serum IgE. These variations are independent of each other and likely to be largely environmental in origin. (J Allergy Clin Immunol 1997;99:314-22.)
Published: 1997

6. Increased risk of type 2 diabetes in antidepressant users: evidence from a 6‐year longitudinal study in the E3N cohort

Author: B. Balkau, Guy Fagherazzi, Agnès Fournier, M. C. Boutron-Ruault, Hermann Nabi, Fabrice Bonnet, M. Azevedo Da Silva, Centre de recherche en épidémiologie et santé des populations (CESP), 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), McGill University = Université McGill [Montréal, Canada], CHU Pontchaillou [Rennes], Faculté de médecine de l'Université Laval [Québec] (ULaval), Centre de recherche du CHU de Québec-Université Laval (CRCHUQ), CHU de Québec–Université Laval, Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval), Luxembourg Institute of Health (LIH), Agence Nationale de la Recherche, ANR: ANR‐10‐COHO‐0006 European Commission, EC: LSHM‐CT‐2006‐037197, M.A.D.S. was the recipient of a doctoral fellowship from the , Paris, France. The E3N cohort is being conducted with the financial support of the , the European Community, the French League against Cancer, Gustave Roussy, and the French Institute of Health and Medical Research. The validation of potential type 2 diabetes cases was supported by the European Union (Integrated Project LSHM‐CT‐2006‐037197 in the 6th European Community Framework Programme). G.F. was supported by a grant for the E4N study from the Agence Nationale de Recherche (ANR‐10‐COHO‐0006 grant), and an IDEX grant (NUTRIPERSO project) from Paris Saclay University. Ministère de l’Enseignement Supérieur et de la Recherche Mutuelle Générale de l'Education Nationale, ANR-10-COHO-0006,E4N,Etude Epidémiologique des Enfants de femmes de l'Education Nationale(2010), HAL UVSQ, Équipe, Cohortes - Etude Epidémiologique des Enfants de femmes de l'Education Nationale - - E4N2010 - ANR-10-COHO-0006 - COHO - VALID, 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), and Université Laval [Québec] (ULaval)
Subjects: Male, Longitudinal study, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, MEDLINE, 030209 endocrinology & metabolism, Context (language use), Type 2 diabetes, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Risk Factors, Internal medicine, Internal Medicine, medicine, Humans, Longitudinal Studies, 030212 general & internal medicine, Aged, Proportional Hazards Models, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, business.industry, Hazard ratio, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Middle Aged, medicine.disease, Antidepressive Agents, 3. Good health, Diabetes Mellitus, Type 2, Cohort, Antidepressant, Female, France, business, Cohort study
Abstract: International audience; Aim: To examine the association between antidepressant medication use and the risk of type 2 diabetes. Methods: Data were obtained from the E3N study (Étude Épidémiologique de Femmes de la Mutuelle Générale de l'Éducation Nationale), a French cohort study initiated in 1990, with questionnaire-based follow-up every 2 or 3 years. Exposure to antidepressants was obtained from drug reimbursement files available from 2004 onwards, and individually matched with questionnaire data. Cases of type 2 diabetes were identified from drug reimbursements. Cox proportional-hazard regression models were used, with drug exposure considered as a time-varying parameter. Results: Of the 63 999 women who were free of drug-treated type 2 diabetes at baseline in 2005, 1124 developed type 2 diabetes over the 6-year follow-up. Current use of antidepressants was associated with an increased risk of type 2 diabetes [hazard ratio 1.34 (95% CI 1.12, 1.61)] compared to non-users. When the different types of antidepressants were considered, women who currently used selective serotonin reuptake inhibitors, imipramine-type, 'other' or 'mixed' antidepressants had a 1.25-fold (95% CI 0.99, 1.57), 1.66-fold (95% CI 1.12, 2.46), 1.35-fold (95% CI 1.00, 1.84) and 1.82-fold (95% CI 0.85, 3.86) increase in risk of type 2 diabetes compared to non-users, respectively. Conclusion: Our study suggests a positive association between antidepressant use and the risk of type 2 diabetes among women. If this association is confirmed, screening and surveillance of glucose levels should be considered in the context of antidepressant therapy. Further studies assessing the underlying mechanisms of this association are needed. (ClinicalTrials.gov identifier: NCT03285230).
Published: 2020
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7. Effects of Maternal Fish Oil and/or 5-Methyl-Tetrahydrofolate Supplementation during Pregnancy on Offspring Brain Resting-State at 10 Years Old: A Follow-Up Study from the NUHEAL Randomized Controlled Trial

Author: Cristina Martínez-Zaldívar, Andrés Catena, Cristina Martín-Pérez, Berthold Koletzko, Daniel Campos, Miguel Pérez-García, José Antonio García-Santos, Cristina Campoy, Hatim Azaryah, Francisco J. Torres-Espínola, Juan Verdejo-Román, [Azaryah,H, García-Santos,JA, Martínez-Zaldívar,C, Torres-Espínola,FJ, Campos,D, Campoy,C] Department of Paediatrics, School of Medicine, University of Granada, Granada, Spain. [Azaryah,H, Campoy,C] EURISTIKOS Excellence Centre for Paediatric Research, Biomedical Research Centre, University of Granada, Granada, Spain. [Verdejo-Román,J, Martin-Pérez,C, Pérez-García,M, Catena,A] Mind, Brain and Behaviour International Research Centre (CIMCYC), University of Granada, Granada, Spain. [García-Santos,JA, Campoy,C] Instituto de Investigación Biosanitaria de Granada (Ibs-GRANADA), Health Sciences Technological Park, Granada, Spain. [Koletzko,B] Ludwig-Maximiliams-Universität München, Dr. von Hauner Children’s Hospital, University of Munich Hospitals, Munich, Germany. [Campoy,C] Spanish Network of Biomedical Research in Epidemiology and Public Health (CIBERESP), Granada’s Node, Institute of Health Carlos III, Madrid, Spain., This work was supported by the Commission of the European Community’s 7th Framework Program (FP7/2008–2013), Grant agreement No. 212652 (NUTRIMENTHE Project), within the 6th Framework Program, Contract no. 007036 (EARNEST Project), and and supported in part by the Commission of the European Community within the 5th Framework Program, Contract No. QLK1-CT-1999-00888 (NUHEAL EU Project). This publication is the work of the authors and does not necessarily reflect the views of the Commission of the European Community. The work of B.K. is supported by the European Research Council Advanced Grant ERC-2012-AdG-No.322605 META-GROWTH. J.V.-R is supported by a grant from the Spanish Ministry of Science, Innovation and Universities (FJCI-2017-33396). The funders had no role in the design, analysis or writing of this article.
Subjects: Male, 0301 basic medicine, Fish oils, Folate, Neurodevelopment, Physiology, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Diagnostic Imaging::Magnetic Resonance Imaging [Medical Subject Headings], Brain function, Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Principal Component Analysis [Medical Subject Headings], fish oil, law.invention, Resting-state functional neuroimaging, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Child Development, 0302 clinical medicine, Randomized controlled trial, law, Pregnancy, Aceites de pescado, Health Care::Environment and Public Health::Public Health::Environmental Pollution::Environmental Exposure::Maternal Exposure [Medical Subject Headings], Child, Children, Tetrahydrofolates, Default mode network, Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Reproductive Physiological Processes::Reproduction::Pregnancy [Medical Subject Headings], Principal Component Analysis, Nutrition and Dietetics, Maternal nutritional physiological phenomena, Fenómenos fisiologicos nutricionales maternos, neurodevelopment, Neuropsychology, Brain, Magnetic Resonance Imaging, 3. Good health, Maternal Exposure, Niño, Technology and Food and Beverages::Food and Beverages::Food::Dietary Supplements [Medical Subject Headings], Regression Analysis, Female, Ácido fólico, pregnancy, lcsh:Nutrition. Foods and food supply, Adult, Anthropology, Education, Sociology and Social Phenomena::Human Activities::Leisure Activities::Relaxation::Rest [Medical Subject Headings], Anatomy::Nervous System::Nerve Net [Medical Subject Headings], Offspring, Embarazo, Phenomena and Processes::Physiological Phenomena::Physiological Processes::Growth and Development::Human Development::Child Development [Medical Subject Headings], Rest, Chemicals and Drugs::Heterocyclic Compounds::Heterocyclic Compounds, 2-Ring::Pteridines::Pterins::Folic Acid::Tetrahydrofolates [Medical Subject Headings], Check Tags::Male [Medical Subject Headings], lcsh:TX341-641, Fish oil, Placebo, folate, Article, Angular gyrus, brain function, 03 medical and health sciences, Fish Oils, children, Chemicals and Drugs::Lipids::Oils::Fish Oils [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Cohort Studies::Longitudinal Studies::Follow-Up Studies [Medical Subject Headings], medicine, Humans, Persons::Persons::Age Groups::Child [Medical Subject Headings], Persons::Persons::Age Groups::Adult [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Statistics as Topic::Regression Analysis [Medical Subject Headings], 030109 nutrition & dietetics, Resting state fMRI, Phenomena and Processes::Physiological Phenomena::Nutritional Physiological Phenomena::Maternal Nutritional Physiological Phenomena [Medical Subject Headings], business.industry, resting-state functional neuroimaging, Maternal Nutritional Physiological Phenomena, Anatomy::Nervous System::Central Nervous System::Brain [Medical Subject Headings], medicine.disease, Check Tags::Female [Medical Subject Headings], Dietary Supplements, Nerve Net, business, 030217 neurology & neurosurgery, Follow-Up Studies, Food Science
Abstract: Recent studies have shown that maternal supplementation with folate and long-chain polyunsaturated fatty acids (LC-PUFAs) during pregnancy may affect children&rsquo, s brain development. We aimed at examining the potential long-term effect of maternal supplementation with fish oil (FO) and/or 5-methyl-tetrahydrofolate (5-MTHF) on the brain functionality of offspring at the age of 9.5&ndash, 10 years. The current study was conducted as a follow-up of the Spanish participants belonging to the Nutraceuticals for a Healthier Life (NUHEAL) project, 57 children were divided into groups according to mother&rsquo, s supplementation and assessed through functional magnetic resonance imaging (fMRI) scanning and neurodevelopment testing. Independent component analysis and double regression methods were implemented to investigate plausible associations. Children born to mothers supplemented with FO (FO and FO + 5-MTHF groups, n = 33) showed weaker functional connectivity in the default mode (DM) (angular gyrus), the sensorimotor (SM) (motor and somatosensory cortices) and the fronto-parietal (FP) (angular gyrus) networks compared to the No-FO group (placebo and 5-MTHF groups, n = 24) (PFWE &lt, 0.05). Furthermore, no differences were found regarding the neuropsychological tests, except for a trend of better results in an object recall (memory) test. Considering the No-FO group, the aforementioned networks were associated negatively with attention and speed-processing functions. Mother&rsquo, s FO supplementation during pregnancy seems to be able to shape resting-state network functioning in their children at school age and appears to produce long-term effects on children&acute, s cognitive processing.
Published: 2020
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8. Childhood and Adult Secondhand Smoke and Type 2 Diabetes in Women

Author: Laura Tondeur, Marie-Christine Boutron-Ruaualt, Guy Fagherazzi, Françoise Clavel-Chapelon, Blandine de Lauzon-Guillain, Martin Lajous, TONDEUR, LAURA, National Institute of Public Health = Instituto Nacional de Salud Pública [Cuernavaca, Mexique] (INSP), Harvard School of Public Health, 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), The E3N study was performed with the financial support of the Mutuelle Générale de l’Education Nationale, European Community, French League against Cancer, Gustave-Roussy Institute, French Institute of Health and Medical Research, and several general councils in France. The validation of potential type 2 diabetes cases was supported by the European Union (Integrated Project LSHM-CT-2006-037197 in the Framework Program 6 of the European Community) InterAct project. M.L. was supported by the National Council for Science and Technology (CONACYT, Mexico) and the Department of Epidemiology at the Harvard School of Public Health., and 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)
Subjects: Adult, Pediatrics, medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Type 2 diabetes, Tobacco smoke, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, Environmental health, Diabetes mellitus, Internal Medicine, medicine, Humans, Prospective Studies, 030212 general & internal medicine, Epidemiology/Health Services Research, Prospective cohort study, Original Research, 2. Zero hunger, Advanced and Specialized Nursing, Smoke, MESH: Humans, business.industry, Hazard ratio, MESH: Adult, medicine.disease, MESH: Prospective Studies, 3. Good health, MESH: France, Diabetes Mellitus, Type 2, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, MESH: Tobacco Smoke Pollution, Red meat, Female, Tobacco Smoke Pollution, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, business, MESH: Female, Body mass index, MESH: Diabetes Mellitus, Type 2
Abstract: OBJECTIVE The objective of this study was to evaluate the relationship between childhood and adult secondhand smoke and type 2 diabetes. RESEARCH DESIGN AND METHODS We conducted a prospective cohort study among 37,343 French women from the E3N-EPIC (Etude Epidémiologique auprès des femmes de la Mutuelle Générale de l’Education Nationale-European Prospective Investigation into Cancer and Nutrition) who never smoked and who were free of type 2 diabetes, cancer, or cardiovascular disease at baseline in 1992. Self-reported childhood secondhand smoke exposure was defined as having at least one parent who smoked. Adult secondhand smoke was defined as the sum of self-reported hours recorded at baseline of exposure to tobacco smoke from a spouse who smoked (or domestic close contact) and from outside the home. RESULTS Between 1992 and 2007, 795 cases of incident type 2 diabetes were identified and validated through a drug reimbursement dataset and a specific questionnaire. Women with at least one parent who smoked appeared to have an 18% higher rate of type 2 diabetes than women with parents who did not smoke (age-adjusted hazard ratio 1.18 [95% CI 1.02–1.36]). Adult secondhand smoke exposure (no exposure versus ≥4 h/day) was associated with an increased rate of type 2 diabetes (1.36 [1.05–1.77], P = 0.002 for trend) after adjusting for parental history of diabetes, education, body silhouette at age 8, childhood secondhand smoke exposure, physical activity, body mass index, hypertension, hypercholesterolemia, menopausal status and hormone use, alcohol intake, and processed red meat and coffee consumption. CONCLUSIONS This prospective analysis suggests that secondhand smoke exposure in childhood and adulthood are associated with a higher rate of type 2 diabetes.
Published: 2013
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9. Penicillin Resistance Compromises Nod1-Dependent Proinflammatory Activity and Virulence Fitness of Neisseria meningitidis

Author: Francina Langa Vives, Aude Antignac, Muhamed-Kheir Taha, Ala-Eddine Deghmane, Anna Skoczynska, Faridabano Nato, Philippe J. Sansonetti, Stephen E. Girardin, Ivo G. Boneca, Lucie Peduto, Françoise Thouron, Martine Fanton d'Andon, Thierry Pedron, Meriem El Ghachi, Marek Szatanik, Dana J. Philpott, Catherine Werts, Lionel LeBourhis, Maria Leticia Zarantonelli, Céline Mulet, Gérard Eberl, Neisseria, Institut Pasteur [Paris], National Reference Centre for Bacterial Meningitis [Warsaw, Poland] (NRCBM), National Medicines Institute - Narodowy Instytut Leków [Warsaw] (NIL), Infections Bactériennes Invasives, Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall (BGPB), Groupe Avenir, Institut National de la Santé et de la Recherche Médicale (INSERM), Pathogénie Microbienne Moléculaire, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Développement des Tissus Lymphoïdes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Centre d'Ingénierie génétique murine - Mouse Genetics Engineering Center (CIGM), Production de Protéines Recombinantes et d'Anticorps (Plate-Forme), Immunité Innée et Signalisation, Chaire Microbiologie et Maladies infectieuses, Collège de France (CdF (institution)), Our research is supported by Institut Pasteur grants (PTR153 and PTR187), an ACI 0321 (Action Concertée Incitative Intégrée Microbiology) Grant from the Ministère chargé de la Recherche (INSERM No. MIC 0321), and a European Research Council starting grant (202283-PGNfromSHAPEtoVIR). A.S. was supported by a Marie Curie Intra-European Fellowship (No. 23188) within the Sixth European Community Framework Programme and Marie Curie European Reintegration Grants (No. 234876) within the Seventh European Community Framework Programme. M.E.G. was supported by an Institut Pasteur Roux fellowship., European Project: 234876,EC:FP7:PEOPLE,FP7-PEOPLE-ERG-2008,NMEN-PBP(2009), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Collège de France - Chaire Microbiologie et Maladies infectieuses
Subjects: Cancer Research, Penicillin Resistance, Virulence, MESH: Nod1 Signaling Adaptor Protein, Biology, Neisseria meningitidis, medicine.disease_cause, Microbiology, MESH: Neisseria meningitidis, Proinflammatory cytokine, Sepsis, 03 medical and health sciences, chemistry.chemical_compound, Mice, MESH: Mutant Proteins, Antibiotic resistance, MESH: Cell Wall, Cell Wall, Virology, Nod1 Signaling Adaptor Protein, Immunology and Microbiology(all), medicine, Animals, Humans, Penicillin-Binding Proteins, MESH: Animals, Pathogen, MESH: Mice, Molecular Biology, 030304 developmental biology, 0303 health sciences, MESH: Penicillin-Binding Proteins, MESH: Humans, 030306 microbiology, medicine.disease, MESH: Penicillin Resistance, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Penicillin, chemistry, Parasitology, Mutant Proteins, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Peptidoglycan, medicine.drug
Abstract: International audience; Neisseria meningitidis is a life-threatening human bacterial pathogen responsible for pneumonia, sepsis, and meningitis. Meningococcal strains with reduced susceptibility to penicillin G (Pen(I)) carry a mutated penicillin-binding protein (PBP2) resulting in a modified peptidoglycan structure. Despite their antibiotic resistance, Pen(I) strains have failed to expand clonally. We analyzed the biological consequences of PBP2 alteration among clinical meningococcal strains and found that peptidoglycan modifications of the Pen(I) strain resulted in diminished in vitro Nod1-dependent proinflammatory activity. In an influenza virus-meningococcal sequential mouse model mimicking human disease, wild-type meningococci induced a Nod1-dependent inflammatory response, colonizing the lungs and surviving in the blood. In contrast, isogenic Pen(I) strains were attenuated for such response and were out-competed by meningococci sensitive to penicillin G. Our results suggest that antibiotic resistance imposes a cost to the success of the pathogen and may potentially explain the lack of clonal expansion of Pen(I) strains.
Published: 2013
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10. Characterization of an extended-spectrum class A β-lactamase from a novel enterobacterial species taxonomically related to Rahnella spp./Ewingella spp

Author: Marie-Frédérique Lartigue, Gaelle Cuzon, Mikhail V. Edelstein, Laurent Poirel, Patrice Nordmann, Sylvain Brisse, Infectiologie et Santé Publique (UMR ISP), Institut National de la Recherche Agronomique (INRA)-Université de Tours, Résistances émergentes aux antibiotiques, Institut National de la Santé et de la Recherche Médicale (INSERM), Faculté de médecine, Université Paris-Sud - Paris 11 (UP11), Smolensk State Medical Academy, Partenaires INRAE, Institut Pasteur [Paris], European Community HEALTH-F3-2001-278232, Institut National de la Recherche Agronomique (INRA)-Université de Tours (UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Paris-Sud - Paris 11 - Faculté de médecine (UP11 UFR Médecine), Génotypage des Pathogènes et Santé Publique (Plate-forme) (PF8), Institut Pasteur [Paris] (IP), This work was partially funded by a grant from the INSERM (UMR914), by the Université Paris-Sud, France, and by grants from the European Community (R-GNOSIS, FP7/HEALTH-F3-2011-282512 and MAGIC-BULLET, FP7/HEALTH-F3-2001-278232)., European Project: 278232,EC:FP7:HEALTH,FP7-HEALTH-2011-two-stage,MAGICBULLET(2012), European Project: 282512,EC:FP7:HEALTH,FP7-HEALTH-2011-single-stage,R-GNOSIS(2011), ProdInra, Migration, Optimisation of treatment with off-patent antimicrobial agents of ventilator-associated pneumonia (VAP) - MAGICBULLET - - EC:FP7:HEALTH2012-01-01 - 2015-12-31 - 278232 - VALID, and Resistance in Gram-Negative Organisms: Studying Intervention Strategies - R-GNOSIS - - EC:FP7:HEALTH2011-10-01 - 2017-03-31 - 282512 - VALID
Subjects: MESH: Sequence Analysis, DNA, Cefotaxime, MESH: Sequence Homology, Amino Acid, Gene Expression, MESH: beta-Lactamases, medicine.disease_cause, extended-spectrum β-lactamases, Plasmid, MESH: Spectrophotometry, Ultraviolet, polycyclic compounds, Pharmacology (medical), Cloning, Molecular, CTX-M, MESH: Enterobacteriaceae Infections, chemistry.chemical_classification, 0303 health sciences, biology, MESH: Escherichia coli, Hydrolysis, Enterobacteriaceae Infections, MESH: Cefotaxime, Chromatography, Ion Exchange, extended-spectrum b-lactamases, Amino acid, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Infectious Diseases, Ewingella americana, MESH: Hydrolysis, medicine.drug, DNA, Bacterial, Microbiology (medical), MESH: Gene Expression, Molecular Sequence Data, Penicillins, Serratia, beta-Lactamases, Microbiology, Gram-negatives, MESH: Enterobacteriaceae, 03 medical and health sciences, Enterobacteriaceae, MESH: Penicillins, Escherichia coli, medicine, Humans, MESH: Cloning, Molecular, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Gene, 030304 developmental biology, Pharmacology, MESH: Molecular Sequence Data, MESH: Humans, Sequence Homology, Amino Acid, 030306 microbiology, Sequence Analysis, DNA, biochemical phenomena, metabolism, and nutrition, bacterial infections and mycoses, biology.organism_classification, MESH: Chromatography, Ion Exchange, MESH: DNA, Bacterial, chemistry, Spectrophotometry, Ultraviolet, Rahnella aquatilis
Abstract: International audience; OBJECTIVES: To characterize the naturally occurring beta-lactamase gene identified from a clinical isolate belonging to a novel enterobacterial species that is closely related to Rahnella spp. and Ewingella spp. METHODS: Shotgun cloning and expression in Escherichia coli were performed in order to characterize this resistance determinant. Enzymatic activities were measured by UV spectrophotometry after an ion-exchange chromatography purification procedure. RESULTS: A chromosomal gene coding for the extended-spectrum beta-lactamase (ESBL) SMO-1 was identified from a novel enterobacterial species that is taxonomically related to Rahnella aquatilis and Ewingella americana. The beta-lactamase efficiently hydrolysed penicillins and cefotaxime, and shared 75% amino acid identity with the plasmid-mediated beta-lactamase SFO-1 from Serratia fonticola, 74% amino acid identity with the plasmid-mediated ESBL CTX-M-2 originating from Kluyvera spp. and 72% amino acid identity with the chromosomally encoded and intrinsic RAHN-1 from R. aquatilis. CONCLUSIONS: We have identified a novel enterobacterial species recovered from a clinical specimen, constituting another potential source of acquired ESBL. The ESBL shared significant similarities with the CTX-M-type enzymes.
Published: 2013
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11. Penicillinase-resistant antibiotics induce non-immune-mediated cholestasis through HSP27 activation associated with PKC/P38 and PI3K/AKT signaling pathways

Author: Burban, Audrey, Sharanek, Ahmad, Hüe, Romain, Gay, Marion, Routier, Sylvain, Guillouzo, André, Guguen-Guillouzo, Christiane, Burban, Audrey, Mechanism-Based Integrated Systems for the Prediction of Drug-Induced Liver Injury - MIP-DILI - - EC:FP7:SP1-JTI2012-02-01 - 2017-01-31 - 115336 - VALID, Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut de Chimie Organique et Analytique (ICOA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université d'Orléans (UO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), This work was supported by the European Community through the Innovative Medicines Initiative Join Undertaking MIP-DILI project [grant agreement number 115336], resources of which are composed of financial contribution from the European Union's Seventh Framework Programme [FP7/20072013] and EFPIA companies’ in kind contribution. Audrey Burban, Ahmad Sharanek and Romain Hüe were financially supported by the MIP-DILI project., European Project: 115336,EC:FP7:SP1-JTI,IMI-JU-03-2010,MIP-DILI(2012), Université de Rennes 1 (UR1) - Institut National de la Santé et de la Recherche Médicale (INSERM) - Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Commissariat à l'énergie atomique et aux énergies alternatives (CEA) - Université d'Orléans (UO) - Centre National de la Recherche Scientifique (CNRS), This work was supported by the European Community through the Innovative Medicines Initiative Joint Undertaking MIP-DILI project [grant agreement number 115336], resources of which are composed of financial contribution from the European Union's Seventh Framework Programme [FP7/20072013] and EFPIA companies’ in kind contribution. Audrey Burban, Ahmad Sharanek and Romain Hüe were financially supported by the MIP-DILI project. We are grateful to Dr Rémy Le Guevel from the ImPACcell platform for imaging analysis., European Project : 115336, EC:FP7:SP1-JTI, IMI-JU-03-2010, MIP-DILI(2012), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université d'Orléans (UO)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut de Chimie du CNRS (INC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: [SDV.SP.MED] Life Sciences [q-bio]/Pharmaceutical sciences/Medication, Cell Survival, MAP Kinase Signaling System, Science, HSP27 Heat-Shock Proteins, Models, Biological, Article, Cell Line, Bile Acids and Salts, Phosphatidylinositol 3-Kinases, Stress, Physiological, Animals, Humans, Phosphorylation, Protein Kinase C, rho-Associated Kinases, Cholestasis, Hepatology, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, [SDV.TOX] Life Sciences [q-bio]/Toxicology, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Hepatocytes, Cytokines, Medicine, Reactive Oxygen Species, beta-Lactamase Inhibitors, Proto-Oncogene Proteins c-akt, Signal Transduction
Abstract: International audience; The bile salt export pump (BSEP), encoded by the abcb11 gene, is the major canalicular transporter of bile acids from the hepatocyte. BSEP malfunction in humans causes bile acid retention and progressive liver injury, ultimately leading to end-stage liver failure. The natural, hydrophilic, bile acid ursodeoxycholic acid (UDCA) is efficacious in the treatment of cholestatic conditions, such as primary biliary cirrhosis and cholestasis of pregnancy. The beneficial effects of UDCA include promoting bile flow, reducing hepatic inflammation, preventing apoptosis, and maintaining mitochondrial integrity in hepatocytes. However, the role of BSEP in mediating UDCA efficacy is not known. Here, we used abcb11 knockout mice (abcb11-/-) to test the effects of acute and chronic UDCA administration on biliary secretion, bile acid composition, liver histology, and liver gene expression. Acutely infused UDCA, or its taurine conjugate (TUDC), was taken up by the liver but retained, with negligible biliary output, in abcb11-/- mice. Feeding UDCA to abcb11-/- mice led to weight loss, retention of bile acids, elevated liver enzymes, and histological damage to the liver. Semiquantitative RT-PCR showed that genes encoding Mdr1a and Mdr1b (canalicular) as well as Mrp4 (basolateral) transporters were upregulated in abcb11-/- mice. We concluded that infusion of UDCA and TUDC failed to induce bile flow in abcb11-/- mice. UDCA fed to abcb11-/- mice caused liver damage and the appearance of biliary tetra- and penta-hydroxy bile acids. Supplementation with UDCA in the absence of Bsep caused adverse effects in abcb11-/- mice.
Published: 2017
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12. Educational level and family structure influence the dietary changes after the diagnosis of type 2 diabetes: evidence from the E3N study

Author: Françoise Clavel-Chapelon, Courtney Dow, Fabrice Bonnet, Guy Fagherazzi, Aurélie Affret, Hélène Bihan, Beverley Balkau, Francesca Mancini, Marie-Christine Boutron-Ruault, 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 d'endocrinologie, diabétologie, maladies métaboliques [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], The E3N cohort is being carried out with the financial support of the 'Mutuelle Générale de l'Education Nationale', European Community, French League against Cancer, Gustave Roussy, and French Institute of Health and Medical Research. This present work was supported by a grant from the World Cancer Research Fund. The validation of potential diabetes cases was supported by the European Union (Integrated Project LSHM-CT-2006-037197 in the 6th European Community Framework Programme) Interaction of Genetic and Lifestyle Factors on the Incidence of Type 2 Diabetes project., 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), and Jonchère, Laurent
Subjects: Gerontology, Blood Glucose, endocrine system diseases, Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Type 2 diabetes, Socioeconomic factors, E3N study, White People, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Diabetes mellitus, Environmental health, Surveys and Questionnaires, medicine, Humans, 030212 general & internal medicine, Prospective Studies, Dietary change, Socioeconomic status, Exercise, Life Style, Family Characteristics, Nutrition and Dietetics, Evidence-Based Medicine, Food frequency, Family structure, business.industry, nutritional and metabolic diseases, Middle Aged, medicine.disease, 3. Good health, Diet, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Diabetes Mellitus, Type 2, Food frequency questionnaires, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Educational Status, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, France, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Follow-Up Studies
Abstract: International audience; Type 2 diabetes (T2D) has no cure but can be controlled by medication, diet, and lifestyle changes. It has been suggested that diabetes dietary self-management is more difficult for people with socioeconomic difficulties. The objective of our study was to test the hypothesis that socioeconomic factors impact the change of diet after T2D diagnosis. The 57 304 French women included in the present study answered food frequency questionnaires in 1993 and 2005 and questionnaires on socioeconomic factors, and were free from T2D in 1993. Between 1993 and 2005, 1249 women developed T2D. Linear regression models evaluated whether having T2D diagnosed had an impact on energy and nutrient intakes and whether socioeconomic factors were implicated. T2D was associated with a reduction of energy (β = -312.54 kJ/d, P < .001), carbohydrate (β = −9.29 g/d, P < .001), lipid (β = −2.01 g/d, P < .001), and alcohol (β = −2.74 g/d, P = .002) intakes, whereas there was no association with changes in protein or fiber intakes. The main socioeconomic factors that had an impact on dietary change were the level of education of T2D patients and whether or not they had a family (having a partner and/or children). The present study provides evidence that socioeconomic factors impact the way people with T2D change their dietary habits after diagnosis. Furthermore, the family plays a crucial role in dietary self-management, probably encouraging T2D patients to follow dietary recommendations.
Published: 2017
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13. A Worldwide Map of Plasmodium falciparum K13-Propeller Polymorphisms

Author: Benoit Witkowski, Hans-Peter Fuehrer, Garib Das Thakur, Céline Barnadas, Djibrine Djalle, Michael Ramharter, Mindy Leelawong, Wasif Ali-Khan, Harald Noedl, Bouasy Hongvanthong, Mohammad Shafiul-Alam, Hypolite Muhindo-Mavoko, Abdillahi Mohamed Hassan, Judith Straimer, Nimol Khim, Kigbafori D. Silué, Kaknika Loch, Barbara H. Stokes, Maria Dorina Bustos, Laura Berne, Dylan R. Pillai, Ayola A. Adegnika, Lin Hua Tang, Rotha Eam, Saorin Kim, Alioune Dieye, Mei Li, Carole E. Eboumbou-Moukoko, Lydie Canier, Marian Warsame, Didier Menard, David A. Fidock, Yap Boum, Lyndes Wini, Abdiqani Sheikh-Omar, Patrick Tshibangu-Wa-Tshibangu, Maman Laminou Ibrahim, Mohammad Jahirul-Karim, Malen Ken, Monique A. Dorkenoo, Sócrates Herrera, Odile Mercereau-Puijalon, Lise Musset, Valentine Duru, Eric Legrand, Maniphone Khanthavong, Pascal Ringwald, Bruno Pradines, Sandrine Houzé, Rachida Tahar, Olukemi K. Amodu, Johann Beghain, Sandie Menard, Liwang Cui, Colin J. Sutherland, Jun Hu Chen, Kesara Na-Bangchang, Khin Lin, Michael Nambozi, Rithea Leang, Jean Christophe Barale, Milijaona Randrianarivelojosia, Marcus V. G. Lacerda, Sophy Chy, Frédéric Ariey, Jean-Bosco Ouédraogo, Isabelle Morlais, Maria de Fátima Ferreira-da-Cruz, Lubin Jiang, Christophe Rogier, Jun Cao, Peter G. Kremsner, Bui Quang-Phuc, Inès Vigan-Womas, Din Syafruddin, Jetsumon Sattabongkot, Shigeyuki Kano, Abebe A. Fola, Louis Collet, Karamoko Niaré, Thierry Fandeur, Sedigheh Zakeri, Sodiomon B. Sirima, Antoine Berry, Jean Baptiste Mazarati, Fe Espino, Ghulam Rahim-Awab, Chanra Khean, Offianan Andre Toure, Institut Pasteur du Cambodge, Réseau International des Instituts Pasteur (RIIP), Génétique et Génomique des Insectes vecteurs, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Centre de Recherche Médicale de Lambaréné, Albert Schweitzer, Leiden University Medical Center (LUMC), Universiteit Leiden, International Centre for Diarrhoeal Disease Research, Bangladesh (ICDDR,B), University of Ibadan, Nangarhar University, Mahidol University [Bangkok], The Walter and Eliza Hall Institute of Medical Research (WEHI), University of Melbourne, Papua New Guinea Institute for Medical Research (PNGIMR), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Mbarara University of Science and Technology [Mbarara] (MUST), Epicentre Ouganda [Mbarara] [Médecins Sans Frontières], Epicentre [Paris] [Médecins Sans Frontières], World Health Organization (WHO), country office for Thailand, Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), JiangSu University, National Institute of Parasitic Diseases, Center for Disease Control, China, Centre Hospitalier de Mayotte, Pennsylvania State University (Penn State), Penn State System, Epidemiology and Disease Control division (EDCD), Ministry of Public Health [Nepal], Institut Pasteur de Dakar, Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD), Institut Pasteur de Bangui, Université de Lomé [Togo], Université de Douala, Centre Pasteur du Cameroun, Research Institute for Tropical Medicine, Centre International de Recherches Médicales de Franceville (CIRMF), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), University of Gondar, Institute of Parasitology [Vienna], University of Veterinary Medicine, Vienna, World Health Organisation (WHO), country office for Somalia, Caucaseco scientific research center = Centro de Investigación Científica Caucaseco, National Center for Malariology, Parasitology and Entomology, Ministry of Health [Mozambique], Hôpital Bichat - Claude Bernard, Mère et enfant en milieu tropical : pathogènes, système de santé et transition épidémiologique (MERIT - UMR_D 216), Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5), Centre de Recherche Médicale et Sanitaire (Niamey, Niger) (CERMES), Directorate General of Health Services (DGHS), Institut Pasteur de Shanghai, Académie des Sciences de Chine - Chinese Academy of Sciences (IPS-CAS), National Center for Global Health and Medicine [Japan] (NCGM), Institut Pasteur du Laos, Instituto Leônidas e Maria Deane - Fiocruz Amazônia [Manaus, Brésil] (ILMD), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD), National Center for Malaria Control, Parasitology and Entomology, Ministry of Health of Cambodgia, Henry M. Jackson Foundation for the Advancement of Military Medicine (HJM), U.S. Naval Medical Research, The Department of Medical Research (Upper Myanmar), Rwanda Biomedical Center (RBC), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement [Yaoundé, Cameroun] (IRD [Cameroun]), Institut de Recherche pour le Développement (IRD), University of Kinshasa (UNIKIN), University of Antwerp (UA), Institut Pasteur de la Guyane, Thammasat University (TU), Tropical Diseases Research Center (TDRC), Université de Bamako, Medizinische Universität Wien = Medical University of Vienna, Institut de Recherche en Sciences de la Santé (IRSS) / Centre Muraz, Medicines for Malaria Venture (MMV), Université de Genève = University of Geneva (UNIGE), Global Malaria Programme, Unité de Recherche sur les Maladies Infectieuses et Tropicales Emergentes (URMITE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR48, Institut des sciences biologiques (INSB-CNRS)-Institut des sciences biologiques (INSB-CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence du Paludisme, Institut Pasteur de Madagascar, Ministry of Health and Human Services [Somalia], Centre Suisse de Recherches Scientifiques en Cote d'Ivoire [Abidjan] (CSRS-CI), Université Félix Houphouët-Boigny (UFHB), Groupe de recherche action en santé (GRAS), London School of Hygiene and Tropical Medicine (LSHTM), University of Hasanuddin, Eijkman Institute for Molecular Biology [Jakarta], Institut Pasteur de Côte d'Ivoire, Ministry of Health and Medical Services, Institut Pasteur d'Iran, Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR - laboratoire associé), Microbiologie structurale - Structural Microbiology (Microb. Struc. (UMR_3528 / U-Pasteur_5)), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Columbia University Irving Medical Center (CUIMC), Institut de Recherche Biomédicale des Armées [Antenne Marseille] (IRBA), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Supported by the Institut Pasteur Paris, Institut Pasteur International Division, Institut Pasteur Cambodia, and the World Health Organization, by a grant (ANR-10-LABX-62-IBEID) from the French Government Investissement d’Avenir program, Laboratoire d’Excellence 'Integrative Biology of Emerging Infectious Diseases', a grant from Natixis Banques, a grant (R01I109023, to Dr. Fidock) from the National Institutes of Health, grants from the Fiocruz Fundação Oswaldo Cruz, Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro, Fundação de Amparo à Pesquisa do Estado do Amazonas, the Brazilian National Council for Scientific and Technological Development, the Agence Nationale de la Recherche (13-BSV3-0018-01 and11-BSV7-009-01), the Austrian Federal Ministry of Science, Research, and Econo-my, the Calgary Laboratory Services, the Centre International de Recherches Médicales de Franceville, the European and Developing Countries Clinical Trials Partnership (CT-2004-31070-001), the Drugs for Neglected Diseases Initiative, the Else Kroener Fresenius Stiftung, the Holger Poehlmann Stiftung, the European Community African–European Research Initiative 'IDEA' (HEALTH-F3-2009-241642), the Fonds Wetenschappelijk Onderzoek, the Vlaamse Interuniversitaire Raad–Universitaire Ontwikkelingssamenwerking, the Belgian Technical Cooperation in Democratic Republic of Congo, the European Community Seventh Framework Program (FP7/2007-2013, 242095, and 223601), the European Commission (REGPOT-CT-2011-285837-STRONGER), the Ministère de la Santé Publique du Niger (Laboratoire National de Référence Résistance aux Antipaludiques), the Foundation of National Science and Technology Major Program (2012ZX10004-220), the French Ministry of Health (Institut National de Veille Sanitaire), the Global Fund to Fight AIDS, Tuberculosis and Malaria, the 5% Initiative program (French Ministry of Foreign Affairs, France Expertise Internationale, 12INI109), the Institut Pasteur de Madagascar, the Government of the Philippines, the Institut de Recherche pour le Développement, the Foundation des Treilles, the Délégation Générale pour l’Armement (PDH-2-NRBC-4-B1-402), the Institut Pasteur de Bangui, the International Society for Health Research and Training, the Malaria Research Initiative Bandarban, Vienna, International Centre for Diarrhoeal Disease Research, Bangladesh, the Médecins sans Frontières (Centre Opérationnel Paris, France), Medicines for Malaria Venture, the National Research Council of Thailand, the Thammasat University, the National Natural Science Foundation of China (81271870, 81361120405, and 81271863), the Natural Science Foundation of Jiangsu Province (BK20130114 and BK20150001), the Jiangsu Science and Technology Department (BM2015024), the National Institutes of Health (R01 AI11646601, AI109023, and ICEMR U19AI089702, U19AI089672), the Pasteur Institute of Iran, the Malaria Division of the Iranian Center for Diseases Management and Control, Public Health England (Malaria Reference Service Contract), the Government of Rwanda, the U.S. Department of Defense Armed Forces Health Surveillance Center, Global Emerging Infections Surveillance and Response System (P0463-14-N6), the Fogarty International Center of the National Institutes of Health training (D43 TW007393), the Mahidol-Oxford Research Unit, the Government of Japan (Science and Technology Agency, Agency for Medical Research and Development, Japan International Cooperation Agency, and Science and Technology Research Partnership for Sustainable Development), and the President’s Malaria Initiative of the U.S. Agency for International Development., The KARMA Consortium, ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), ANR-13-BSV3-0018,MALARTRES,Résistance de Plasmodium aux antipaludiques de la famille des artémisinines(2013), ANR-13-BSV7-0009,NEBEDIV,Le rôle des ennemis naturels dans la diversité béta des arbres tropicaux(2013), European Project: CT-2004-31070-001,EDCCTP, European Project: HEALTH-F3-2009-24164,IDEA, European Project: FP7/2007-2013, 24209,FP7, European Project: FP7/2007-2013, 22360,FP7, European Project: 285837,EC:FP7:REGPOT,FP7-REGPOT-2011-1,STRONGER(2011), European Project: 242095,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,EVIMALAR(2009), European Project: 223601,EC:FP7:HEALTH,FP7-HEALTH-2007-B,MALVECBLOK(2009), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse], Fundação Oswaldo Cruz (FIOCRUZ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Genève (UNIGE), INSB-INSB-Centre National de la Recherche Scientifique (CNRS), Centre National de Référence du Paludisme [Cayenne, Guyane française] (CNR), Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Eberhard Karls Universität Tübingen, The Walter and Eliza Hall Institute of Medical Research, Melbourne, Australia., Centre International de Recherches Médicales de Franceville, Caucaseco scientific research center, Mère et enfant face aux infections tropicales (MERIT - UMR_D 216), National Center for Global Health and Medicine (NCGM), Instituto Leônidas e Maria Deane (ILMD), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement [Yaoundé], Centre Suisse de Recherches Scientifiques en Côte d'Ivoire, Eijkman Institute for Molecular Biology, Laboratoire de Parasitologie, Centre National de Référence du Paludisme - Région Antilles-Guyane, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-WHO Collaborating Center for Surveillance of Antimalarial Drug Resistance, Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), ANR-10-LABX-62-IBEID,IBEID,Laboratoire d'Excellence 'Integrative Biology of Emerging Infectious Diseases'(2010), Van geertruyden, Jean-Pierre, and KARMA Consortium
Subjects: 0301 basic medicine, Nonsynonymous substitution, MESH: Sequence Analysis, DNA, Endemic Diseases, MESH: Asia, Southeastern, Drug Resistance, Protozoan Proteins, Drug resistance, MESH: Genotype, Lactones, 0302 clinical medicine, Genotype, Artemisinin, Malaria, Falciparum, MESH: Protozoan Proteins, Asia, Southeastern, MESH: Plasmodium falciparum, Genetics, biology, MESH: Malaria, Falciparum, General Medicine, Artemisinins, MESH: China, 3. Good health, MESH: Endemic Diseases, MESH: Drug Resistance, Algorithms, MESH: Lactones, medicine.drug, China, MESH: Mutation, 030231 tropical medicine, 030106 microbiology, Plasmodium falciparum, MESH: Algorithms, 03 medical and health sciences, parasitic diseases, MESH: Artemisinins, MESH: Polymorphism, Genetic, medicine, Humans, [SDV.MP.PAR]Life Sciences [q-bio]/Microbiology and Parasitology/Parasitology, Allele, Polymorphism, Genetic, MESH: Humans, Haplotype, Sequence Analysis, DNA, medicine.disease, biology.organism_classification, Virology, Mutation, Human medicine, Malaria
Abstract: Comment inK13-Propeller Mutations and Malaria Resistance, http://www.nejm.org/doi/full/10.1056/NEJMe1604520; International audience; BACKGROUND:Recent gains in reducing the global burden of malaria are threatened by the emergence of Plasmodium falciparum resistance to artemisinins. The discovery that mutations in portions of a P. falciparum gene encoding kelch (K13)-propeller domains are the major determinant of resistance has provided opportunities for monitoring such resistance on a global scale.METHODS:We analyzed the K13-propeller sequence polymorphism in 14,037 samples collected in 59 countries in which malaria is endemic. Most of the samples (84.5%) were obtained from patients who were treated at sentinel sites used for nationwide surveillance of antimalarial resistance. We evaluated the emergence and dissemination of mutations by haplotyping neighboring loci.RESULTS:We identified 108 nonsynonymous K13 mutations, which showed marked geographic disparity in their frequency and distribution. In Asia, 36.5% of the K13 mutations were distributed within two areas--one in Cambodia, Vietnam, and Laos and the other in western Thailand, Myanmar, and China--with no overlap. In Africa, we observed a broad array of rare nonsynonymous mutations that were not associated with delayed parasite clearance. The gene-edited Dd2 transgenic line with the A578S mutation, which expresses the most frequently observed African allele, was found to be susceptible to artemisinin in vitro on a ring-stage survival assay.CONCLUSIONS:No evidence of artemisinin resistance was found outside Southeast Asia and China, where resistance-associated K13 mutations were confined. The common African A578S allele was not associated with clinical or in vitro resistance to artemisinin, and many African mutations appear to be neutral. (Funded by Institut Pasteur Paris and others.).
Published: 2016
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14. Generalization of motor resonance during the observation of hand, mouth, and eye movements

Author: Marco Jacono, Alessandra Finisguerra, Thierry Pozzo, Laura Maffongelli, Michela Bassolino, Alessandro D'Ausilio, Department of Robotics, Brain and Cognitive Sciences ( RBCS ), Istituto Italiano di Tecnologia ( IIT ), Dipartimento di Scienze Umane, Università degli Studi di Udine - University of Udine [Italie], Center for Neuroprosthetics and Institute of Bioengineering, EPFL., Cognition, Action, et Plasticité Sensorimotrice [Dijon - U1093] ( CAPS ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), and European Community grant SIEMPRE [Information and Communication Technologies (ICT)-Future and Emerging Technologies] (grant number 250026)European Community grant CAPES-COFECUB (grant 819-14)La Fondation Motrice with the 'Pace for CP program' European Community grant POETICON++ (Specific Targeted Research Project ICT) (grant 288382)
Subjects: Male, motor generalization, synergies, Eye Movements, Physiology, representation, muscle, medicine.medical_treatment, Motion Perception, Video Recording, Electromyography, system, Motor Activity, Eye, NO, Fingers, Young Adult, Motor system, excitability, Accelerometry, medicine, Humans, Motion perception, action observation network, Set (psychology), goal, Mouth, medicine.diagnostic_test, General Neuroscience, Motor Cortex, Eye movement, Evoked Potentials, Motor, Transcranial Magnetic Stimulation, Biomechanical Phenomena, Transcranial magnetic stimulation, modulation, medicine.anatomical_structure, cortex, Higher Neural Functions and Behavior, Action (philosophy), [ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], finger movements, Female, corticospinal excitability, Psychology, Neuroscience, finger kinematics, Motor cortex
Abstract: International audience; Transcranial magnetic stimulation (TMS) of the motor cortex shows that hand action observation (AO) modulates corticospinal excitability (CSE). CSE modulation alternatively maps low-level kinematic characteristics or higher-level features, like object-directed action goals. However, action execution is achieved through the control of muscle synergies, consisting of coordinated patterns of muscular activity during natural movements, rather than single muscles or object-directed goals. This synergistic organization of action execution also underlies the ability to produce the same functional output (i.e., grasping an object) using different effectors. We hypothesize that motor system activation during AO may rely on similar principles. To investigate this issue, we recorded both hand CSE and TMS-evoked finger movements which provide a much more complete description of coordinated patterns of muscular activity. Subjects passively watched hand, mouth and eyelid opening or closing, which are performing non-object-directed (intransitive) actions. Hand and mouth share the same potential to grasp objects, whereas eyelid does not allow object-directed (transitive) actions. Hand CSE modulation generalized to all effectors, while TMS evoked finger movements only to mouth AO. Such dissociation suggests that the two techniques may have different sensitivities to fine motor modulations induced by AO. Differently from evoked movements, which are sensitive to the possibility to achieve object-directed action, CSE is generically modulated by "opening" vs. "closing" movements, independently of which effector was observed. We propose that motor activities during AO might exploit the same synergistic mechanisms shown for the neural control of movement and organized around a limited set of motor primitives.
Published: 2015
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15. Allo-Immune Membranous Nephropathy and Recombinant Aryl Sulfatase Replacement Therapy: A Need for Tolerance Induction Therapy

Author: Laure-Hélène Noël, Vassili Valayannopoulos, Pierre Ronco, Niaudet P, Olivia Boyer, Patrice Callard, Pascale de Lonlay, Hanna Debiec, Hélène Sarda, Remodelage et Reparation du Tissu Renal, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de référence pour les maladies métaboliques héréditaires [CHU Necker Enfants Malades - AP-HP], Université Paris Descartes - Paris 5 (UPD5)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Néphropathies héréditaires et rein en développement (UMR_S 983), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Necker - Enfants Malades [AP-HP], Centre de recherche Croissance et signalisation (UMR_S 845), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Pédiatrie [CH René Dubos, Pontoise], Centre Hospitalier René Dubos [Pontoise], Research is supported by European Research Council Grant ERC-2012-ADG_20120314 (Grant Agreement 322947), Agence Nationale pour la Recherche Programme Blanc SVSE1 (2012) Decision ANR-12-BSE1-0002-01, Fondation pour la Recherche Médicale Equipe FRM 2012 grant, and 7th Framework Programme of the European Community Contract 2012-305608 (European Consortium for High-Throughput Research in Rare Kidney Diseases)., European Project: 322947,EC:FP7:ERC,ERC-2012-ADG_20120314,OSAI(2013), European Project: 305608,EC:FP7:HEALTH,FP7-HEALTH-2012-INNOVATION-1,EURENOMICS(2012), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'anatomie pathologique [CHU Necker], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de pédiatrie, Hopital Réné Dubos-CH Pontoise, European Research Council Grant ERC-2012-ADG_20120314 (Grant Agreement 322947), Agence Nationale pour la Recherche Programme Blanc SVSE1 (2012) Decision ANR-12-BSE1-0002-01, Fondation pour la Recherche Médicale Equipe FRM 2012 grant, and 7th Framework Programme of the European Community Contract 2012-305608 (European Consortium for High-Throughput Research in Rare KidneyDiseases)., Service de Néphrologie et Dialyses [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Pathologie [CHU Tenon], RONCO, Pierre, Membranous nephropathy : a model for solving organ-specific auto-immunity (OSAI) - OSAI - - EC:FP7:ERC2013-05-01 - 2018-04-30 - 322947 - VALID, European Consortium for High-Throughput Research in Rare Kidney Diseases - EURENOMICS - - EC:FP7:HEALTH2012-10-01 - 2017-09-30 - 305608 - VALID, Service de Département de Néphrologie = Service de Néphrologie et Dialyses [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Centre National de la Recherche Scientifique ( CNRS ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris Descartes - Paris 5 ( UPD5 ), Néphropathies héréditaires et rein en développement ( UMR_S 983 ), CHU Necker - Enfants Malades [AP-HP]-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Assistance publique - Hôpitaux de Paris (AP-HP), Centre de recherche Croissance et signalisation ( UMR_S 845 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Service de Pathologie, Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Service de néphrologie, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Tenon [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Male, N-Acetylgalactosamine-4-Sulfatase, Mucopolysaccharidosis type VI, MESH: Glomerulonephritis, Membranous, MESH : Child, Preschool, MESH : N-Acetylgalactosamine-4-Sulfatase, Gastroenterology, Glomerulonephritis, Membranous, MESH: Recombinant Proteins, 0302 clinical medicine, Isoantibodies, Medicine, MESH : Glomerulonephritis, Membranous, MESH: Enzyme Replacement Therapy, 0303 health sciences, Proteinuria, Mucopolysaccharidosis VI, MESH : Enzyme Replacement Therapy, MESH : Immune Tolerance, Glomerulonephritis, General Medicine, Enzyme replacement therapy, Recombinant Proteins, 3. Good health, Tolerance induction, Nephrology, [ SDV.BBM.GTP ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Child, Preschool, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine.symptom, Brief Communications, medicine.medical_specialty, MESH: Immune Tolerance, MESH: Mucopolysaccharidosis VI, MESH : Recombinant Proteins, MESH : Male, MESH : Isoantibodies, MESH: N-Acetylgalactosamine-4-Sulfatase, Nephropathy, 03 medical and health sciences, Membranous nephropathy, Internal medicine, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Immune Tolerance, Humans, Enzyme Replacement Therapy, 030304 developmental biology, MESH: Humans, business.industry, MESH : Humans, MESH: Child, Preschool, medicine.disease, MESH: Isoantibodies, MESH: Male, MESH : Mucopolysaccharidosis VI, Immunology, business, Nephrotic syndrome, 030217 neurology & neurosurgery
Abstract: International audience; Nephrotic syndrome was reported in a highly-sensitized patient receiving enzyme replacement therapy (ERT) for Pompe disease, but the prevalence of ERT-induced renal complications and mechanisms to facilitate readministration of ERT in these patients remain unexplored. This work identifies a new antigen responsible for secondary membranous nephropathy (MN) in a patient with mucopolysaccharidosis type VI caused by aryl sulfatase B (ASB) deficiency. ERT (recombinant human ASB [rhASB]; 1 mg/kg per week) started at the age of 4 years led to a high anti-rhASB titer and dramatically improved clinical manifestations. However, 16 months later, the patient suddenly developed nephrotic syndrome resistant to steroid therapy 1 week after orthopedic surgery. Examination of the kidney biopsy specimen revealed glomerular deposition of IgG (mostly IgG4, C3, and C5b-9) in a granular pattern typical of MN. Double immunofluorescence staining showed that subepithelial granular deposits contained rhASB colocalized with IgG. Ig eluted from the patient's biopsy specimen reacted specifically with rhASB. On discontinuation of ERT, proteinuria progressively decreased, but the patient's clinical condition markedly deteriorated. Induction of tolerance to rhASB was initiated by coadministration of low-dose corticosteroids, rituximab, intravenous Igs, and oral methotrexate. ERT was resumed 8 weeks after starting immunosuppressive therapy without inducing a rebound of antibody titer or an increase in proteinuria. We conclude that the allo-immune response to the recombinant rhASB caused the nephropathy. Considering the critical requirement for ERT in patients with such enzyme deficiencies, immune tolerance induction should be advocated in the patients with allo-immune MN.
Published: 2014
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16. Association between melanocytic nevi and risk of breast diseases: The French E3N prospective cohort

Author: Sylvie Mesrine, Françoise Clavel-Chapelon, Alice Vilier, Laure Dossus, Laura Baglietto, Anne Bijon, Marie-Christine Boutron-Ruault, Marina Kvaskoff, Agnès Fournier, 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), Division of Cardiovascular Medicine and Channing Division of Network Medicine, Brigham and Women's Hospital [Boston], Cancer Control Group, QIMR Berghofer Medical Research Institute, Cancer Epidemiology Centre, The Cancer Council Victoria, Centre for Molecular , Environmental, Genetic and Analytic (MEGA) Epidemiology, University of Melbourne-Centre for Molecular, Melbourne School of Population Health, This work was supported by the Mutuelle Generale de l’Education Nationale (MGEN), the European Community, the French League against Cancer (LNCC), Gustave Roussy, and the French National Institutes for Health and Medical Research (Inserm)). MK is financially supported by a Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme (#PIOF-GA-2011-302078) (URL: http://ec.europa.eu/research/mariecurieactions/about-mca/actions/iof, Dupuis, Christine, and 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)
Subjects: Oncology, Adult, medicine.medical_specialty, Skin Neoplasms, [SDV]Life Sciences [q-bio], Breast Neoplasms, Family, Female, France, Humans, Logistic Models, Melanocytes, Middle Aged, Nevus, Premenopause, Proportional Hazards Models, Prospective Studies, Risk Factors, Medicine (all), lcsh:Medicine, Breast cancer, Internal medicine, Medicine and Health Sciences, medicine, Family history, skin and connective tissue diseases, 10. No inequality, Prospective cohort study, Gynecology, business.industry, lcsh:R, Absolute risk reduction, Cancer, General Medicine, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Perspective, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Breast disease, Skin cancer, business
Abstract: Background: While melanocytic nevi have been associated with genetic factors and childhood sun exposure, several observations also suggest a potential hormonal influence on nevi. To test the hypothesis that nevi are associated with breast tumor risk, we explored the relationships between number of nevi and benign and malignant breast disease risk. Methods and Findings: We prospectively analyzed data from E3N, a cohort of French women aged 40–65 y at inclusion in 1990. Number of nevi was collected at inclusion. Hazard ratios (HRs) for breast cancer and 95% confidence intervals (CIs) were calculated using Cox proportional hazards regression models. Associations of number of nevi with personal history of benign breast disease (BBD) and family history of breast cancer were estimated using logistic regression. Over the period 15 June 1990–15 June 2008, 5,956 incident breast cancer cases (including 5,245 invasive tumors) were ascertained among 89,902 women. In models adjusted for age, education, and known breast cancer risk factors, women with ‘‘very many’’ nevi had a significantly higher breast cancer risk (HR=1.13, 95% CI=1.01–1.27 versus ‘‘none’’; ptrend=0.04), although significance was lost after adjustment for personal history of BBD or family history of breast cancer. The 10-y absolute risk of invasive breast cancer increased from 3,749 per 100,000 women without nevi to 4,124 (95% CI=3,674–4,649) per 100,000 women with ‘‘very many’’ nevi. The association was restricted to premenopausal women (HR=1.40, ptrend=0.01), even after full adjustment (HR=1.34, ptrend=0.03; phomogeneity=0.04), but did not differ according to breast cancer type or hormone receptor status. In addition, we observed significantly positive dose–response relationships between number of nevi and history of biopsy-confirmed BBD (n=5,169; ptrend,0.0001) and family history of breast cancer in first-degree relatives (n=7,472; ptrend=0.0003). The main limitations of our study include self-report of number of nevi using a qualitative scale, and self-reported history of biopsied BBD. Conclusions: Our findings suggest associations between number of nevi and the risk of premenopausal breast cancer, BBD, and family history of breast cancer. More research is warranted to elucidate these relationships and to understand their underlying mechanisms. Please see later in the article for the Editors’ Summary.
Published: 2014
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17. Structural and Mechanical Heterogeneity of the Erythrocyte Membrane Reveals Hallmarks of Membrane Stability

Author: Laura Picas, Simon Scheuring, Maxime Deforet, Felix Rico, BIO-AFM-LAB Bio Atomic Force Microscopy Laboratory (Bio-AFM-Lab), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Physico-Chimie-Curie (PCC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), This study was supported by the Institut Curie, the Institut National de la Santé et Recherche Médicale (INSERM), the Agence Nationale de la Recherche (ANR), and the City of Paris, and a Fondation Pierre-Gilles de Gennes Fellowship (to LP) and a European Community Marie Curie Intra-European Fellowship for Career Development (to FR)., Aix-Marseille Université, Laboratoire U1006, Institut National de la Santé et de la Recherche Médicale (INSERM) - Aix Marseille Université (AMU), Université Pierre et Marie Curie - Paris 6 (UPMC) - INSTITUT CURIE - Centre National de la Recherche Scientifique (CNRS), This study was supported by the Institut Curie, the Institut National de la Santé et RechercheMédicale (INSERM), the Agence Nationale de la Recherche (ANR), and the City of Paris, and aFondation Pierre-Gilles de Gennes Fellowship (to LP) and a European Community Marie CurieIntra-European Fellowship for Career Development (to FR)., Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC), Compartimentation et dynamique cellulaires (CDC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Adhésion et Inflammation (LAI), Assistance Publique - Hôpitaux de Marseille (APHM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Jean Perrin (LJP), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Department of Physiology and Biophysics, University of Miami Leonard M. Miller School of Medicine (UMMSM), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), and Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cytoplasm, General Physics and Astronomy, [SDV.BBM.BP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, 02 engineering and technology, Biology, 03 medical and health sciences, Adenosine Triphosphate, atomic force microspcopy, Cell cortex, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, General Materials Science, Spectrin, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Protein–lipid interaction, Phosphorylation, Integral membrane protein, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Mechanical Phenomena, 0303 health sciences, atomic force microscopy, Peripheral membrane protein, Erythrocyte Membrane, General Engineering, EPB41, Membrane Proteins, Membrane transport, 021001 nanoscience & nanotechnology, Cell biology, Biomechanical Phenomena, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, Membrane, spectrin, erythrocyte, 0210 nano-technology, Extracellular Space, [PHYS.COND.CM-SCM]Physics [physics]/Condensed Matter [cond-mat]/Soft Condensed Matter [cond-mat.soft], mechanics
Abstract: International audience; A n essential feature of red blood cells (RBCs) relies on their capability to undergo large passive deformations throughout narrow capillaries of the micro-vasculature during their 120-days life span. Mature erythrocytes are non-nucleated, and their structural integrity depends on the particular attributes of the plasma membrane in terms of antigenic and transport activity but importantly, on its remarkable mechanical properties. 1 Many studies have unraveled the complexity hidden in the exceptional properties of the erythrocyte plasma membrane thanks to the development of isolation methods and techniques for the biochemical, structural, and functional characterization of the diverse components that integrate the erythrocyte membrane. 1À5 The RBC membrane consists of an R and β-spectrin lattice that is linked to the lipid bilayer thought membrane proteins, most of them integrating multiprotein complexes. The most abundant membrane proteins are band 3, aquaporin-1, glycophorin A and C, and the rhesus proteins, Rh and RhAG. Key for the structural integrity of the membrane are two macromolecular complexes: the an-kyrin-based complex, which is thought to work as a metabolon, and the 4.1R complex that integrates the main components of the skeleton network junctions, i.e. spectrin, actin, and protein 4.1R, together with other proteins (adducin, tropomyosin, topo-modulin, p55, and demantin) and membrane proteins such as glycophorin C (GPC) or band 3 (for a review see ref 1). It is well established, that far from being static, the RBC membrane is a metabolically regulated active structure. 5 Thus, a number of works have shown the regulatory mechanism of Ca 2þ , phosphatidylinositol 4,5-bisphos-phate (PIP 2), or protein phosphorylation on the membrane. As a result, posttranslational modifications of proteins integrating the * Address correspondence to simon.scheuring@inserm.fr.
Published: 2013
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18. The Impact of Human Conflict on the Genetics of Mastomys natalensis and Lassa Virus in West Africa

Author: Raphaël Leblois, Jan ter Meulen, Christiane Denys, Aude Lalis, Emilie Lecompte, Thierry Wirth, Muséum national d'Histoire naturelle (MNHN), Département Systématique et Évolution, Centre de Biologie pour la Gestion des Populations (UMR CBGP), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de la Recherche Agronomique (INRA)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Evolution et Diversité Biologique (EDB), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Philipps University of Marburg, Institut für Virologie, Philipps University, Laboratoire de Biologie Intégrative des Populations, École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), This study was supported by the European Community (INCO-DEV grant ICA-CT2002-10050), a Marie Curie Intra-European fellowship within the 6th European Community Framework Programme MEIF-CT2003-506686, and the Howard Hughes Medical Institute. The authors are particularly indebted to the 'Projet de Recherches sur les Fièvres Hémorragiques en Guinée' for their contribution in the fieldwork.., Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Philipps Universität Marburg = Philipps University of Marburg, and École Pratique des Hautes Études (EPHE)
Subjects: Evolutionary Genetics, Viral Diseases, Disease reservoir, Epidemiology, lcsh:Medicine, medicine.disease_cause, 0302 clinical medicine, Zoonoses, lcsh:Science, Lassa fever, Genome Evolution, Refugees, 0303 health sciences, Multidisciplinary, Ecology, biology, [SDV.BID.EVO]Life Sciences [q-bio]/Biodiversity/Populations and Evolution [q-bio.PE], Genomics, Infectious Diseases, Emerging infectious disease, Medicine, Research Article, Warfare, 030231 tropical medicine, Nigeria, Rodentia, Context (language use), Microbiology, Communicable Diseases, Viral Evolution, Sierra leone, 03 medical and health sciences, Lassa Fever, Virology, Genetics, medicine, Animals, Humans, Natural reservoir, Lassa virus, Biology, Disease Reservoirs, 030304 developmental biology, Evolutionary Biology, [SDV.GEN.GPO]Life Sciences [q-bio]/Genetics/Populations and Evolution [q-bio.PE], Population Biology, lcsh:R, Computational Biology, Genetic Variation, Genomic Evolution, Bayes Theorem, 15. Life on land, medicine.disease, biology.organism_classification, Emerging Infectious Diseases, Genetics, Population, Nucleoproteins, Evolutionary Ecology, 13. Climate action, Mastomys, Microbial Evolution, lcsh:Q, Guinea, Murinae, Zoology
Abstract: International audience; Environmental changes have been shown to play an important role in the emergence of new human diseases of zoonotic origin. The contribution of social factors to their spread, especially conflicts followed by mass movement of populations, has not been extensively investigated. Here we reveal the effects of civil war on the phylogeography of a zoonotic emerging infectious disease by concomitantly studying the population structure, evolution and demography of Lassa virus and its natural reservoir, the rodent Mastomys natalensis, in Guinea, West Africa. Analysis of nucleoprotein gene sequences enabled us to reconstruct the evolutionary history of Lassa virus, which appeared 750 to 900 years ago in Nigeria and only recently spread across western Africa (170 years ago). Bayesian demographic inferences revealed that both the host and the virus populations have gone recently through severe genetic bottlenecks. The timing of these events matches civil war-related mass movements of refugees and accompanying environmental degradation. Forest and habitat destruction and human predation of the natural reservoir are likely explanations for the sharp decline observed in the rodent populations, the consequent virus population decline, and the coincident increased incidence of Lassa fever in these regions. Interestingly, we were also able to detect a similar pattern in Nigeria coinciding with the Biafra war. Our findings show that anthropogenic factors may profoundly impact the population genetics of a virus and its reservoir within the context of an emerging infectious disease.
Published: 2012
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19. Processed and Unprocessed Red Meat Consumption and Incident Type 2 Diabetes Among French Women

Author: Martin Lajous, Marie-Christine Boutron-Ruaualt, Françoise Clavel-Chapelon, Blandine de Lauzon-Guillain, Guy Fagherazzi, Laura Tondeur, Harvard School of Public Health, National Institute of Public Health = Instituto Nacional de Salud Pública [Cuernavaca, Mexique] (INSP), 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), This E3N cohort was performed with the financial support of the Mutuelle Générale de l’Education Nationale, European Community, French League Against Cancer, Gustave Roussy Institute, French Institute of Health and Medical Research, and several general councils in France. The validation of potential diabetes cases was supported by the European Union (Integrated Project LSHM-CT-2006-037197 in Framework Program 6 of the European Community) InterAct project. The present analysis was conducted thanks to the International Associated Laboratory in Nutrition, Hormones, and Chronic Disease in Women, an ongoing collaboration between the National Institute of Health and Medical Research (INSERM, France) and the National Institute of Public Health (INSP, Mexico). M.L. was supported by the National Council for Science and Technology (Mexico), the INSP, the Ministry of Health (Mexico), the Department of Epidemiology at the Harvard School of Public Health, and the Bernard Lown Fund for Cardiovascular Health in the Developing World. G.F. was funded by the French Ministry of Research., TONDEUR, LAURA, and 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)
Subjects: MESH: Meat Products, Calorie, 030309 nutrition & dietetics, Endocrinology, Diabetes and Metabolism, Type 2 diabetes, Cohort Studies, 0302 clinical medicine, Surveys and Questionnaires, Prospective Studies, MESH: Incidence, Prospective cohort study, MESH: Cohort Studies, Original Research, 2. Zero hunger, MESH: Meat, 0303 health sciences, MESH: Middle Aged, Incidence, Middle Aged, 3. Good health, Menopause, Meat Products, Red Meat Consumption, Red meat, MESH: Feeding Behavior, Female, France, Cohort study, MESH: Diabetes Mellitus, Type 2, medicine.medical_specialty, Meat, 030209 endocrinology & metabolism, 03 medical and health sciences, Environmental health, Diabetes mellitus, Internal Medicine, medicine, Humans, Epidemiology/Health Services Research, MESH: Surveys and Questionnaires, Advanced and Specialized Nursing, MESH: Humans, business.industry, Feeding Behavior, medicine.disease, MESH: Prospective Studies, Surgery, MESH: France, Diabetes Mellitus, Type 2, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Female
Abstract: OBJECTIVE To evaluate the relation of processed and unprocessed red meat and incident type 2 diabetes. RESEARCH DESIGN AND METHODS We conducted a prospective study among 66,118 disease-free French women with dietary information from a validated questionnaire. Between 1993 and 2007, we identified 1,369 cases of incident diabetes. Multivariate analyses were adjusted for age, education, region, smoking, BMI, hypertension, hypercholesterolemia, physical activity, parental history of diabetes, menopause, hormone replacement therapy, alcohol, calories, n-3 fatty acids, carbohydrates, coffee, fiber, and fruits and vegetables. RESULTS Comparing the highest category of processed meat intake, ≥5 servings/week (median, 48 g/day), to the lowest, CONCLUSIONS In this large prospective cohort of French women, a direct association was observed only for processed red meat and type 2 diabetes.
Published: 2012
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20. Colonization of dermal arterioles by Neisseria meningitidis provides a safe haven from neutrophils

Author: Manriquez, Valeria, Nivoit, Pierre, Urbina, Tomas, Echenique-Rivera, Hebert, Melican, Keira, Fernandez-Gerlinger, Marie-Paule, Flamant, Patricia, Schmitt, Taliah, Bruneval, Patrick, Obino, Dorian, Duménil, Guillaume, Obino, Dorian, Integrative Biology of Emerging Infectious Diseases - - IBEID2010 - ANR-10-LABX-0062 - LABX - VALID, Blood vessels as a target for infection - VIP - - EC:FP7:ERC2013-01-01 - 2017-12-31 - 310790 - VALID, Functional Genomics Analysis of Neisseria meningitidis interactions with human dermal blood vessels in vivo - HUVASC-SEQ - - EC:FP7:PEOPLE2014-06-01 - 2016-05-31 - 624740 - VALID, Pathogénèse des Infections vasculaires / Pathogenesis of Vascular Infections, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Karolinska Institutet [Stockholm], Neuropathologie expérimentale / Experimental neuropathology, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Centre hospitalier Saint-Joseph [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), This work was supported by the Integrative Biology of Emerging Infectious Diseases (IBEID) laboratory of excellence (ANR-10-LABX-62), and the VIP European Research Council-starting grant (310790-VIP, G.D.). D.O. was supported by a Pasteur-Roux Postdoctoral Fellowship from the Institut Pasteur. H.E.-R. was supported by a Marie Curie Intra-European Fellowship within the 7th project European Community Framework Program (624740)., The authors thank Elisa Gomez Perdiguero, Molly Ingersoll, Ana-Maria Lennon-Duménil, and Benoît Marteyn for fruitful discussions and critical reading of the manuscript. We would like to thank Maxime Gauberti for his insights into the expression of human inflammatory adhesion receptors. We also thank Albane Imbert (FabLab Institut Pasteur (FLIP), DRTE, Institut Pasteur, Paris, France) for 3D-printing, Michael Hivelin (Hôpital Européen Georges Pompidou) for providing skin samples, Sophie Novault (Cytometry and Biomarkers UTechS, Institut Pasteur, Paris, France) for technical advice, Eric Camerer (UMR-970, Paris-Cardiovascular Research Center PARCC, Paris, France) for technical advice on vascular permeability experiments and the members of the UtechS Photonic BioImaging (Imagopole, C2RT, Institut Pasteur, Paris, France), supported by the French National Research Agency (France BioImaging, ANR-10–INSB–04, investments for the Future) for assistance in image acquisition and analysis., ANR-10-LABX-0062,IBEID,Integrative Biology of Emerging Infectious Diseases(2010), European Project: 310790,EC:FP7:ERC,ERC-2012-StG_20111109,VIP(2013), European Project: 624740,EC:FP7:PEOPLE,FP7-PEOPLE-2013-IEF,HUVASC-SEQ(2014), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut Pasteur [Paris]-Université de Paris (UP)
Subjects: Adult, Male, Bacterial immune evasion, Time Factors, [SDV.IMM] Life Sciences [q-bio]/Immunology, Neutrophils, Science, Colony Count, Microbial, Mice, SCID, Neisseria meningitidis, Article, Bacterial Adhesion, Young Adult, Phagocytosis, Animals, Humans, Cellular microbiology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Inflammation, Dermis, Middle Aged, Capillaries, Up-Regulation, Meningococcal Infections, Arterioles, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Neutrophil Infiltration, Fimbriae, Bacterial, Heterografts, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Endothelium, Vascular, Bacterial infection, Pathogens, E-Selectin, Cell Adhesion Molecules
Abstract: The human pathogen Neisseria meningitidis can cause meningitis and fatal systemic disease. The bacteria colonize blood vessels and rapidly cause vascular damage, despite a neutrophil-rich inflammatory infiltrate. Here, we use a humanized mouse model to show that vascular colonization leads to the recruitment of neutrophils, which partially reduce bacterial burden and vascular damage. This partial effect is due to the ability of bacteria to colonize capillaries, venules and arterioles, as observed in human samples. In venules, potent neutrophil recruitment allows efficient bacterial phagocytosis. In contrast, in infected capillaries and arterioles, adhesion molecules such as E-Selectin are not expressed on the endothelium, and intravascular neutrophil recruitment is minimal. Our results indicate that the colonization of capillaries and arterioles by N. meningitidis creates an intravascular niche that precludes the action of neutrophils, resulting in immune escape and progression of the infection., The human pathogen Neisseria meningitidis colonizes blood vessels and causes vascular damage, despite a neutrophil-rich inflammatory infiltrate. Here, Manriquez et al. use a humanized mouse model to show that pathogen colonization of capillaries and arterioles creates an intravascular niche that precludes an effective action of neutrophils.
Published: 2021
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21. Birth weight, body silhouette over the life course, and incident diabetes in 91,453 middle-aged women from the French Etude Epidemiologique de Femmes de la Mutuelle Generale de l'Education Nationale (E3N) Cohort.: Body silhouette history and incident diabetes

Author: Marie-Aline Charles, Marie-Christine Boutron-Ruault, Beverley Balkau, Isabelle Romieu, Blandine de Lauzon-Guillain, Françoise Clavel-Chapelon, Nutrition, hormones et cancer: épidémiologie et prévention (E3N), Epidémiologie, sciences sociales, santé publique (IFR 69), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-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)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-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)-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Recherche en épidémiologie et biostatistique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), National Institute of Public Health = Instituto Nacional de Salud Pública [Cuernavaca, Mexique] (INSP), This work was carried out with the financial support of the 'Mutuelle Générale de l'Education Nationale' (MGEN), European Community, French League against Cancer (LNCC), Gustave Roussy Institute (IGR), French Institute of Health and Medical Research (Inserm), and several General Councils in France. The validation of potential diabetes cases was supported by the European Union (Integrated Project LSHM-CT-2006-037197 in the Framework Program 6 of the European-Community), InterAct project., and Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-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)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris-Sud - Paris 11 (UP11)-École des hautes études en sciences sociales (EHESS)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Gustave Roussy (IGR)-Université Paris-Sud - Paris 11 (UP11)
Subjects: Male, Pediatrics, Body Surface Area, Endocrinology, Diabetes and Metabolism, Type 2 diabetes, Weight Gain, MESH: Regression Analysis, Body Mass Index, MESH: Proportional Hazards Models, Cohort Studies, MESH: Body Surface Area, 0302 clinical medicine, Surveys and Questionnaires, Birth Weight, Body Size, 030212 general & internal medicine, Young adult, MESH: Cohort Studies, Original Research, adiposity, MESH: Middle Aged, MESH: Infant, Newborn, Middle Aged, 3. Good health, MESH: Young Adult, Cohort, MESH: Weight Gain, Regression Analysis, epidemiology, France, medicine.symptom, Cohort study, Adult, medicine.medical_specialty, MESH: Diabetes Mellitus, longitudinal, Birth weight, MESH: Infant, Low Birth Weight, 030209 endocrinology & metabolism, MESH: Body Mass Index, 03 medical and health sciences, Young Adult, Thinness, Internal Medicine, medicine, Diabetes Mellitus, Humans, MESH: Birth Weight, Epidemiology/Health Services Research, Proportional Hazards Models, Advanced and Specialized Nursing, MESH: Thinness, MESH: Body Size, MESH: Humans, business.industry, MESH: Questionnaires, Infant, Newborn, MESH: Adult, Infant, Low Birth Weight, medicine.disease, MESH: Male, Middle age, MESH: France, Low birth weight, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Body mass index, Demography
Abstract: OBJECTIVE Obesity and increases in body weight in adults are considered to be among the most important risk factors for type 2 diabetes. Low birth weight is also associated with a higher diabetes incidence. We aimed to examine to what extent the evolution of body shape, from childhood to adulthood, is related to incident diabetes in late adulthood. RESEARCH DESIGN AND METHODS Etude Epidemiologique de Femmes de la Mutuelle Générale de l'Education Nationale (E3N) is a cohort study of French women born in 1925–1950 and followed by questionnaire every 2 years. At baseline, in 1990, women were asked to report their current weight, height, and body silhouette at various ages. Birth weight was recorded in 2002. Cases of diabetes were self-reported or obtained by drug reimbursement record linkage and further validated. RESULTS Of the 91,453 women who were nondiabetic at baseline, 2,534 developed diabetes over the 15 years of follow-up. Birth weight and body silhouette at 8 years, at menarche, and in young adulthood (20–25 years) were inversely associated with the risk of diabetes, independently of adult BMI during follow-up (all Ptrend < 0.001). In mid-adulthood (35–40 years), the association was reversed, with an increase in risk related to a larger body silhouette. An increase in body silhouette from childhood to mid-adulthood amplified the risk of diabetes. CONCLUSIONS Low birth weight and thinness until young adulthood may increase the risk of diabetes, independently of adult BMI during follow-up. Young women who were lean children should be especially warned against weight gain.
Published: 2009
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22. Human Splicing Finder: an online bioinformatics tool to predict splicing signals

Author: Marine Lalande, Christophe Béroud, François Olivier Desmet, Dalil Hamroun, Gwenaëlle Collod-Béroud, Mireille Claustres, Laboratoire de génétique des maladies rares. Pathologie moleculaire, etudes fonctionnelles et banque de données génétiques (LGMR), IFR3, Université Montpellier 1 (UM1)-Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), European Community Seventh Framework Program (FP7/2007-2013) under grant agreement number 200754—the GEN2PHEN project, The European Community Sixth Framework Program (FP6) under grant agreement number 036825, TREAT-NMD Network of Excellence. Funding for open access, European Project: 200754,EC:FP7:HEALTH,FP7-HEALTH-2007-A,GEN2PHEN(2008), Université Montpellier 1 (UM1)-IFR3, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), COLLOD-BEROUD, Gwenaëlle, and Genotype-To-Phenotype Databases: A Holistic Solution - GEN2PHEN - - EC:FP7:HEALTH2008-01-01 - 2013-06-30 - 200754 - VALID
Subjects: Exonic splicing enhancer, [SDV.GEN] Life Sciences [q-bio]/Genetics, Biology, Bioinformatics, 03 medical and health sciences, Exon, User-Computer Interface, 0302 clinical medicine, Genetics, Silencer Elements, Transcriptional, Humans, splice, 030304 developmental biology, Ribonucleoprotein, 0303 health sciences, Internet, [SDV.GEN]Life Sciences [q-bio]/Genetics, Splice site mutation, Sequence Analysis, RNA, Intron, Computational Biology, Exon skipping, Enhancer Elements, Genetic, RNA splicing, Mutation, Methods Online, RNA Splice Sites, Databases, Nucleic Acid, 030217 neurology & neurosurgery, Software
Abstract: International audience; Thousands of mutations are identified yearly. Although many directly affect protein expression, an increasing proportion of mutations is now believed to influence mRNA splicing. They mostly affect existing splice sites, but synonymous, non-synonymous or nonsense mutations can also create or disrupt splice sites or auxiliary cis-splicing sequences. To facilitate the analysis of the different mutations, we designed Human Splicing Finder (HSF), a tool to predict the effects of mutations on splicing signals or to identify splicing motifs in any human sequence. It contains all available matrices for auxiliary sequence prediction as well as new ones for binding sites of the 9G8 and Tra2-beta Serine-Arginine proteins and the hnRNP A1 ribonucleoprotein. We also developed new Position Weight Matrices to assess the strength of 5' and 3' splice sites and branch points. We evaluated HSF efficiency using a set of 83 intronic and 35 exonic mutations known to result in splicing defects. We showed that the mutation effect was correctly predicted in almost all cases. HSF could thus represent a valuable resource for research, diagnostic and therapeutic (e.g. therapeutic exon skipping) purposes as well as for global studies, such as the GEN2PHEN European Project or the Human Variome Project.
Published: 2009
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23. Toll-like receptor 5- and lymphotoxin beta receptor-dependent epithelial Ccl20 expression involves the same NF-kappaB binding site but distinct NF-kappaB pathways and dynamics

Author: Martín Rumbo, Frederic Sierro, Delphine Cayet, Jean-Claude Sirard, Arnaud Didierlaurent, Sirard, Jean-Claude, Interactions cellulaires et moléculaires des bactéries pathogènes avec l'hôte, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Kennedy Institute of Rheumatology, Imperial College London, Department of Immunology and Inflammation, Garvan Institute of medical research, Laboratorio de Investigaciones en el Sistema Inmune (LISIN), Facultad de Ciencias Exactas [La Plata], Universidad Nacional de la Plata [Argentine] (UNLP)-Universidad Nacional de la Plata [Argentine] (UNLP), and JCS and DC are funded by INSERM (including Avenir grant R02344ES), the Institut Pasteur de Lille, the Région Nord Pas de Calais and FEDER (ARCir Emergence/ARCir Europe), the Franco-Argentinean ECOS-SETCIP program (A04B03) and the European Community (STREP grant SavinMucoPath INCO-CT-2006-032296). MR is member of CONICET and funded by National Agency of Promotion of Science and Technology (ANPCYT-PICT34679), CONICET (PIP5241) and the European Community (STREP grant SavinMucoPath INCO-CT-2006-032296).
Subjects: MESH: Signal Transduction, MESH: Mucosal Tracts Infections, MESH: NF-kappa B, Gene Expression, MESH: Lymphotoxin beta Receptor, MESH: Base Sequence, Lymphotoxin beta, Biochemistry, chemistry.chemical_compound, Mice, Structural Biology, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Animals, Promoter Regions, Genetic, RELB, NF-kappa B, hemic and immune systems, MESH: Toll-Like Receptor 5, NF-kappa-B, Chemokine, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Intestinal Mucosa, [SDV.IMM]Life Sciences [q-bio]/Immunology, MESH: Caco-2 Cells, Protein Binding, Signal Transduction, Gene isoform, MESH: Cell Nucleus, MESH: Gene Expression, [SDV.IMM] Life Sciences [q-bio]/Immunology, Medicina, Molecular Sequence Data, Biophysics, Active Transport, Cell Nucleus, chemical and pharmacologic phenomena, MESH: Active Transport, Cell Nucleus, Biology, Cell Line, MESH: Mice, Inbred C57BL, Toll-like receptor, Lymphotoxin beta Receptor, MESH: Promoter Regions, Genetic, Genetics, MESH: Protein Binding, Animals, Humans, Binding site, Molecular Biology, MESH: Mice, Ciencias Exactas, Cell Nucleus, MESH: Humans, MESH: Molecular Sequence Data, Binding Sites, Chemokine CCL20, Base Sequence, MESH: Mucous Membrane, NF-κB, MESH: Chemokine CCL20, Molecular biology, MESH: Cell Line, CCL20, Mice, Inbred C57BL, Toll-Like Receptor 5, Lymphotoxin, chemistry, MESH: Binding Sites, MESH: Immunity, Mucosal, Caco-2 Cells, Lymphotoxin beta receptor, MESH: Flagellin, Flagellin
Abstract: Canonical and alternative NF-κB pathways depend on distinct NF-κB members and regulate expression of different gene subset in inflammatory and steady state conditions, respectively. In intestinal epithelial cells, both pathways control the transcription of the gene coding the CCL20 chemokine. Lymphotoxin β receptor (LTβR) mediates long lasting CCL20 expression whereas Toll-like receptor 5 (TLR5) signals promote inducible and transient activation. Here, we investigated whether the regulation of CCL20 expression involves different promoter sites and NF-κB molecules in response to TLR5 and LTβR stimulation. In epithelial cells, both stimulation required the same promoter regions, especially the NF-κB binding site but involved different NF-κB isoforms: p65/p50 and p52/RelB, for TLR5 and LTβR-dependent activation, respectively. The dynamic of activation and interaction with CCL20-specific NF-κB site correlated with gene transcription. Similar Ccl20 expression and NF-κB activation was found in the small intestine of mice stimulated with TLR5 and LTβR agonists. In summary, different NF-κB pathways modulate CCL20 transcription by operating on the same NF-κB binding site in the same cell type., Facultad de Ciencias Exactas, Laboratorio de Investigaciones del Sistema Inmune
Published: 2008
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24. Antiviral-resistant hepatitis B virus: can we prevent this monster from growing?

Author: Fabien Zoulim, Anna S.F. Lok, Maria Buti, Service d'Hépatologie, Hospices Civils de Lyon (HCL), Virus des hépatites et pathologies associées, Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Hospital General, Vall d'Hebron University Hospital [Barcelona], Division of Gastroenterology, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, F. Zoulim receives grant from INSERM and the European Community (VIRGIL Network of Excellence, grant LSHM-CT-2004-503359). A. S. Lok is partially funded by an NIH grant U01 DK57577 M. Buti receives grant from the European Community (VIRGIL Network of Excellence, grant LSHM-CT-2004-503359 and CIBER-Hepad)., and Zoulim, Fabien
Subjects: Drug, medicine.drug_class, media_common.quotation_subject, Drug resistance, Biology, Virus Replication, medicine.disease_cause, 03 medical and health sciences, Liver disease, Hepatitis B, Chronic, 0302 clinical medicine, antivirals, Drug Resistance, Multiple, Viral, Virology, antiviral therapy, medicine, Animals, Humans, Potency, 030304 developmental biology, media_common, Hepatitis B virus, 0303 health sciences, drug resistance, Hepatology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, Infectious Diseases, Immunology, 030211 gastroenterology & hepatology, chronic hepatitis, Antiviral drug, Viral load, hepatitis B virus, Biomedical sciences
Abstract: International audience; Despite the recent progress in antiviral therapy of chronic hepatitis B, clinical experience has shown that antiviral drug resistance is inevitable with the administration of nucleoside analog monotherapy. The long-term persistence of the viral genome in infected cells and the high rate of spontaneous mutation is the basis for the selection of HBV mutants that are resistant to polymerase inhibitors. Selection of antiviral-resistant mutations leads to a rise in viral load and progression of liver disease. The incidence of antiviral resistance depends on the potency and genetic barrier to resistance of the antiviral drug, highlighting the importance of the choice if first line therapy. The determination of cross-resistance profile of each drug has allowed the design of rescue therapy for patients with virologic breakthrough. Early diagnosis and treatment intervention allow the majority of patients to maintain in clinical remission despite the occurrence of drug resistance. Clinical studies are ongoing to determine the best strategy to prevent or delay antiviral drug resistance and of its impact on liver disease.
Published: 2007
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25. Long-term air pollution exposure, greenspace and health-related quality of life in the ECRHS study

Author: Anne, Boudier, Iana, Markevych, Bénédicte, Jacquemin, Michael J, Abramson, Simone, Accordini, Bertil, Forsberg, Elaine, Fuertes, Judith, Garcia-Aymerich, Joachim, Heinrich, Ane, Johannessen, Bénédicte, Leynaert, Isabelle, Pin, Valérie, Siroux, Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), CHU Grenoble, Uniwersytet Jagielloński w Krakowie = Jagiellonian University (UJ), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Monash university, Università degli studi di Verona = University of Verona (UNIVR), Umeå University, Imperial College London, Instituto de Salud Global - Institute For Global Health [Barcelona] (ISGlobal), Universitat Pompeu Fabra [Barcelona] (UPF), Ludwig-Maximilians University [Munich] (LMU), University of Bergen (UiB), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre Hospitalier Universitaire [Grenoble] (CHU), The present analyses are part of the NEVADA project funded by the French Direction Générale de l'Offre de Soin (DGOS), call PHRC-2012.The local investigators and funding agencies for the European Community Respiratory Health Survey (ECRHS I, ECRHS II and ECRHS III) are reported in the online supplementary file.Coordination of the ECRHS I was supported by the European Commission as part of the 'Quality of Life' program and the authors and participants are grateful to the late C. Baya and M. Hallen for their help during the study and K. Vuylsteek and the members of the COMAC for their support. Coordination of the ECRHS II was supported by the European Commission as part of the 'Quality of Life' program (Grant: QLK4-CT-1999-01237). The coordination of the ECRHS 3 was funded through the Medical Research Council (Grant: 92091). NDVI calculations were conducted within the framework of the Ageing Lungs In European Cohorts study that was funded by the European Union's Horizon 2020 research and innovation program under (Grant: 633212). Iana Markevych is currently supported from the 'NeuroSmog: Determining the impact of air pollution on the developing brain' (Nr. POIR.04.04.00-1763/18-00) which is implemented as part of the TEAM-NET programme of the Foundation for Polish Science, co-financed from EU resources, obtained from the European Regional Development Fund under the Smart Growth Operational Programme. ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation through the 'Centro de Excelencia Severo Ochoa 2019–2023' Program (CEX2018-000806-S), and the Generalitat de Catalunya through the CERCA Program., and Jonchère, Laurent
Subjects: Adult, Male, Environmental Engineering, greenness, PM, Epidemiology, Parks, Recreational, [SDV]Life Sciences [q-bio], Nitrogen Dioxide, Well-being, NO(2), NO2, rhinitis, well-being, Air Pollution, Humans, Environmental Chemistry, European Union, Waste Management and Disposal, Rhinitis, Air Pollutants, asthma, greenness, NO2, PM, well-being, Environmental Exposure, asthma, Health Surveys, Pollution, Asthma, [SDV] Life Sciences [q-bio], Greenness, Quality of Life, Female, Particulate Matter, epidemiology
Abstract: International audience; BACKGROUND: Associations of long-term exposure to air pollution and greenspace with health-related quality of life (HRQOL) are poorly studied and few studies have accounted for asthma-rhinitis status. OBJECTIVE: To assess the associations of air pollution and greenspace with HRQOL and whether asthma and/or rhinitis modify these associations. METHODS: The study was based on the participants in the second (2000-2002, n = 6542) and third (2011-2013, n = 3686) waves of the European Community Respiratory Health Survey (ECRHS) including 19 centres. The mean follow-up time was 11.3 years. HRQOL was assessed by the SF-36 Physical and Mental Component Summary scores (PCS and MCS). NO(2), PM(2.5) and PM(10) annual concentrations were estimated at the residential address from existing land-use regression models. Greenspace around the residential address was estimated by the (i) mean of the Normalized Difference Vegetation Index (NDVI) and by the (ii) presence of green spaces within a 300 m buffer. Associations of each exposure variable with PCS and MCS were assessed by mixed linear regression models, accounting for the multicentre design and repeated data, and adjusting for potential confounders. Analyses were stratified by asthma-rhinitis status. RESULTS: The mean (SD) age of the ECRHS-II and III participants was 43 (7.1) and 54 (7.2) years, respectively, and 48 % were men. Higher NO(2), PM(2.5) and PM(10) concentrations were associated with lower MCS (regression coefficients [95%CI] for one unit increase in the inter-quartile range of exposures were -0.69 [-1.23; -0.15], -1.79 [-2.88; -0.70], -1.80 [-2.98; -0.62] respectively). Higher NDVI and presence of forests were associated with higher MCS. No consistent associations were observed for PCS. Similar association patterns were observed regardless of asthma-rhinitis status. CONCLUSION: European adults who resided at places with higher air pollution and lower greenspace were more likely to have lower mental component of HRQOL. Asthma or rhinitis status did not modify these associations.
Published: 2022
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26. DC-SIGN promotes exogenous MHC-I-restricted HIV-1 antigen presentation

Author: Olivier Schwartz, Françoise Porrot, Arnaud Moris, Jean-Pierre Abastado, Florence Buseyne, Cinzia Nobile, Virus et Immunité, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Supported by grants from the Agence Nationale de Recherche sur le SIDA (ANRS), SIDACTION, the European Community, and Institut Pasteur. A.M. is a former fellow of European Community funding (QLK2-CT 2000-01630), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: HIV Antigens, [SDV]Life Sciences [q-bio], Immunology, Antigen presentation, HIV Core Protein p24, Receptors, Cell Surface, Major histocompatibility complex, Biochemistry, Major Histocompatibility Complex, 03 medical and health sciences, 0302 clinical medicine, Viral envelope, Antigen, Antigens, CD, MHC class I, HLA-A2 Antigen, Cytotoxic T cell, Humans, Lectins, C-Type, 030304 developmental biology, 0303 health sciences, Antigen Presentation, biology, Antigen processing, Histocompatibility Antigens Class I, Virion, Cell Biology, Hematology, Dendritic Cells, Virology, 3. Good health, Cell biology, DC-SIGN, CD4 Antigens, biology.protein, HIV-1, Cell Adhesion Molecules, 030215 immunology
Abstract: Dendritic cells (DCs) facilitate HIV-1 spread in the host by capturing virions and transferring them to permissive lymphocytes in lymphoid organs. Lectins such as DC-specific ICAM-grabbing non-integrin (DC-SIGN) are involved in HIV-1 uptake by DCs, through high-affinity binding to viral envelope glycoproteins. We examined the role of DC-SIGN on the fate of incoming virions and on major histocompatibility complex class I (MHC-I)–restricted HIV-1 antigen presentation. We show that DC-SIGN expression in B-cell lines dramatically enhances viral internalization. In these cells, and also in primary DCs, most of the captured virions are rapidly degraded, likely in a lysosomal compartment. In addition, a fraction of incoming viral material is processed by the proteasome, leading to activation of anti–HIV-specific cytotoxic T lymphocytes (CTLs) by DC-SIGN–expressing cells. In DCs, DC-SIGN is not the only receptor involved, and redundant pathways of virus capture leading to antigen presentation likely coexist. Altogether, our results highlight new aspects of DC-SIGN interactions with HIV-1. The lectin does not significantly protect captured virions against degradation and promotes MHC-I exogenous presentation of HIV-1 antigens.
Published: 2003
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27. Inhibition of human immunodeficiency virus type 1 Env-mediated fusion by DC-SIGN

Author: Nathalie Sol-Foulon, Arnaud Moris, Françoise Porrot, Olivier Schwartz, Cinzia Nobile, Virus et Immunité, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), A.M. is a fellow of European Community funding (QLK2-CT 2000-01630). This work was supported by grants from the Agence Nationale de Recherche sur le SIDA (ANRS), SIDACTION, the European Community, and Institut Pasteur., and Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)
Subjects: media_common.quotation_subject, [SDV]Life Sciences [q-bio], viruses, Immunology, Receptors, Cell Surface, Microbiology, Giant Cells, Membrane Fusion, Virus, 03 medical and health sciences, 0302 clinical medicine, Viral entry, Virology, Macrophage, Humans, Lectins, C-Type, Internalization, 030304 developmental biology, media_common, 0303 health sciences, Syncytium, biology, Virion, Lipid bilayer fusion, Gene Products, env, Dendritic cell, 3. Good health, Virus-Cell Interactions, DC-SIGN, Insect Science, CD4 Antigens, biology.protein, HIV-1, Cell Adhesion Molecules, 030215 immunology, HeLa Cells
Abstract: DC-SIGN, a lectin expressed on dendritic cell and macrophage subsets, binds to human immunodeficiency virus Env glycoproteins, allowing capture of viral particles. Captured virions either infect target cells or are efficiently transmitted to lymphocytes. Cellular mechanisms underlying the effects of DC-SIGN remain poorly understood. Here we have analyzed the effects of DC-SIGN on viral entry and on syncytium formation induced by Env glycoproteins. The lectin enhanced susceptibility to viral infection and dramatically increased virion internalization. Captured virions accumulated in the vesicular pathway, and their access to the cytosol was altered. Strikingly, the presence of DC-SIGN on target cells inhibited their ability to form syncytia with Env-expressing cells. However, increasing CD4 surface levels on target cells alleviated this inhibitory effect of DC-SIGN. Moreover, the potency of the viral fusion inhibitor T-20 was not affected in DC-SIGN-expressing cells. Altogether, our results indicate that DC-SIGN exerts subtle and complex effects during early steps of HIV type 1 replication. DC-SIGN facilitates capture and accumulation of viral particles in a vesicular compartment and inhibits viral fusion. Competition between CD4 and DC-SIGN for Env binding likely affects virus access to the cytosol and syncytium formation.
Published: 2003
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28. Infectious hepatitis C virus pseudo-particles containing functional E1-E2 envelope protein complexes

Author: Jean Dubuisson, Birke Bartosch, François-Loïc Cosset, Virologie humaine, École normale supérieure - Lyon (ENS Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Assemblage et réplication du virus de l'hépatite C (ARVHC), Centre National de la Recherche Scientifique (CNRS), This work was supported by Agence Nationale pour la Recherche contre le SIDA, the European Community (contracts QLK3 1999–00859 and QLK2-1999-00356), Association pour la Recherche contre le Cancer, Rescov National Hepatite C, Institut Pasteur de Lille, CNRS, and INSERM (Action Thematique Concertee 'Hepatite C'). B. Bartosch is supported by a Marie Curie Fellowship from the European Community, École normale supérieure de Lyon (ENS de Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), and Cosset, François-Loïc
Subjects: Hepacivirus, receptor, medicine.disease_cause, viral assembly, 0302 clinical medicine, Viral Envelope Proteins, Genes, Reporter, Tumor Cells, Cultured, Immunology and Allergy, hepatitis, Cells, Cultured, glycoproteins, chemistry.chemical_classification, Infectivity, 0303 health sciences, biology, Hepatitis A, virus diseases, Hepatitis C, 3. Good health, 030211 gastroenterology & hepatology, medicine.drug_class, Hepatitis C virus, Recombinant Fusion Proteins, Immunology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Monoclonal antibody, Tetraspanin 28, 03 medical and health sciences, Antigens, CD, Neutralization Tests, medicine, Animals, Humans, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, 030304 developmental biology, Viral Structural Proteins, Virus Assembly, Virion, Membrane Proteins, neutralization, medicine.disease, biology.organism_classification, Virology, digestive system diseases, NS2-3 protease, chemistry, Receptors, LDL, Hepatocytes, Hepatitis C Antigens, Glycoprotein, CD81
Abstract: The study of hepatitis C virus (HCV), a major cause of chronic liver disease, has been hampered by the lack of a cell culture system supporting its replication. Here, we have successfully generated infectious pseudo-particles that were assembled by displaying unmodified and functional HCV glycoproteins onto retroviral and lentiviral core particles. The presence of a green fluorescent protein marker gene packaged within these HCV pseudo-particles allowed reliable and fast determination of infectivity mediated by the HCV glycoproteins. Primary hepatocytes as well as hepato-carcinoma cells were found to be the major targets of infection in vitro. High infectivity of the pseudo-particles required both E1 and E2 HCV glycoproteins, and was neutralized by sera from HCV-infected patients and by some anti-E2 monoclonal antibodies. In addition, these pseudo-particles allowed investigation of the role of putative HCV receptors. Although our results tend to confirm their involvement, they provide evidence that neither LDLr nor CD81 is sufficient to mediate HCV cell entry. Altogether, these studies indicate that these pseudo-particles may mimic the early infection steps of parental HCV and will be suitable for the development of much needed new antiviral therapies.
Published: 2003
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29. Managing the challenge of drug-induced liver injury: a roadmap for the development and deployment of preclinical predictive models

Author: Raymond Pieters, Klaus Gjervig Jensen, Philip G. Hewitt, Jan Snoeys, Bob van de Water, B. Kevin Park, Ursula Klingmüller, André Guillouzo, Ian M. Copple, Dominic P. Williams, Michael J. Liguori, Cerys A. Lovatt, Paul Morgan, Satu Juhila, Eric A.G. Blomme, Magnus Ingelman-Sundberg, Dean J. Naisbitt, Gilles Labbe, Amy E. Chadwick, Christopher E. Goldring, Helga H.J. Gerets, Richard J. Weaver, Jonchère, Laurent, Mechanism-Based Integrated Systems for the Prediction of Drug-Induced Liver Injury - MIP-DILI - - EC:FP7:SP1-JTI2012-02-01 - 2017-01-31 - 115336 - VALID, University of Liverpool, Nutrition, Métabolismes et Cancer (NuMeCan), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Merck Research Laboratories, Karolinska Institutet [Stockholm], Division Systems Biology of Signal Transduction, German Cancer Research Center (DKFZ), German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), SANOFI Recherche, Abbvie Inc. [North Chicago], GlaxoSmithKline, Glaxo Smith Kline, AstraZeneca, University Medical Center [Utrecht], Janssen Research & Development, Leiden University, Institut de Recherches Internationales Servier [Suresnes] (IRIS), UCB BioPharma [Braine l’Alleud, Belgium], This work was supported by the European Community (Contract MIP-DILI-115336) under the Innovative Medicines Initiative Joint Undertaking, a contribution from the European Union's Seventh Framework Programme (FP7/20072013) and European Federation of Pharmaceutical Industries and Associations (EFPIA) companies (http://www.imi.europa.eu/) and by the German Ministry of Education and Research (BMBF) within ‘Multi-Scale Modeling of Drug-Induced Liver Injury’ (MS_DILI, 031L0074A)., European Project: 115336,EC:FP7:SP1-JTI,IMI-JU-03-2010,MIP-DILI(2012), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and Universiteit Leiden
Subjects: 0301 basic medicine, Drug, Drug-Related Side Effects and Adverse Reactions, [SDV]Life Sciences [q-bio], media_common.quotation_subject, In vitro model, 03 medical and health sciences, Preclinical research, 0302 clinical medicine, Predictive Value of Tests, Drug Discovery, Animals, Humans, Medicine, media_common, Pharmacology, Adverse effects, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, General Medicine, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, 3. Good health, [SDV] Life Sciences [q-bio], Disease Models, Animal, 030104 developmental biology, Risk analysis (engineering), Software deployment, Preclinical testing, 030220 oncology & carcinogenesis, Chemical and Drug Induced Liver Injury, business
Abstract: International audience; Drug-induced liver injury (DILI) is a patient-specific, temporal, multifactorial pathophysiological process that cannot yet be recapitulated in a single in vitro model. Current preclinical testing regimes for the detection of human DILI thus remain inadequate. A systematic and concerted research effort is required to address the deficiencies in current models and to present a defined approach towards the development of new or adapted model systems for DILI prediction. This Perspective defines the current status of available models and the mechanistic understanding of DILI, and proposes our vision of a roadmap for the development of predictive preclinical models of human DILI.
Published: 2019
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30. Emergent Shapes of Trait-Based Competition Functions from Resource-Based Models: A Gaussian Is Not Normal in Plant Communities

Author: Mark Westoby, Richard G. FitzJohn, Daniel S. Falster, Georges Kunstler, Evolution & Ecology ResearchCentre and School of Biological, Earth and Environmental Sciences, University of New South Wales [Sydney] (UNSW), Laboratoire des EcoSystèmes et des Sociétés en Montagne (UR LESSEM), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Department of Infectious Disease Epidemiology [London] (DIDE), Imperial College London, Department of Biological Sciences [New South Wales, Australia] (Macquarie University), Macquarie University, and Australian Research Council : FL100100080Australian Research Council : FT160100113Marie Curie International Outgoing Fellowship within the 7th European Community Framework Program (Demo-Traits project) : 299340French National Research Agency (ANR) : ANR-20-CES32-0005-01
Subjects: 0106 biological sciences, Ecology, Community, Fitness landscape, media_common.quotation_subject, coexistence, Function (mathematics), Plants, 15. Life on land, resource, 010603 evolutionary biology, 01 natural sciences, Unimodality, Competition (biology), Phenotype, Resource (project management), Econometrics, Trait, Per capita, Humans, [SDE.BE]Environmental Sciences/Biodiversity and Ecology, competition, Ecology, Evolution, Behavior and Systematics, Mathematics, media_common
Abstract: International audience; In community ecology, it is widely assumed that organisms with similar traits compete more intensely with one another for resources. This assumption is often encoded into theory and empirical tests via a unimodal competition function, which predicts that per capita competitive effect declines with separation in traits. Yet it remains unknown how well this function represents the true effect of traits on competitive outcomes, especially for long-lived plant communities, where lifetime fitness is difficult to estimate. Here, we evaluate the shape of competition functions embedded in two resource-based (RB) models, wherein plants compete for shared, essential resources. In the first RB model individuals compete for two essential nutrients, and in the second they compete for light in a size-based successional setting. We compared the shapes of the competition functions that emerged from interactions within these RB models to the unimodal function and others shapes commonly applied. In few instances did the trait-based competition function emerging from the RB model even vaguely resemble any of the shapes previously used. The mismatch between these two approaches suggests that theory derived using fixed competition functions based on trait separation may not apply well to plant systems, where individuals compete for shared resources. The more promising path will be to model depletion of resources by populations in relation to their traits, with its consequences for fitness landscapes and competitive exclusion.
Published: 2021
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31. Comparison of a Barcode-Based Smartphone Application to a Questionnaire to Assess the Use of Cleaning Products at Home and Their Association with Asthma Symptoms

Author: Lemire, Pierre, Temam, Sofia, Quinot, Catherine, Sévin, Etienne, Remacle, Sophie, Supernant, Karine, Dumas, Orianne, Le Moual, Nicole, Eyriey, E., Licinia, A., Vellement, A., Pin, Isabelle, Hofmann, P., Hullo, Églantine, Llerena, Catherine, Morin, X., Morlot, A., Lepeule, Johanna, Lyon-Caen, Sarah, Philippat, Claire, Quentin, Joane, Siroux, Valérie, Slama, Rémy, Faraldo, Beatrice, Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, MGEN Foundation for Public Health [Paris] (FESP-MGEN), Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), EpiConcept [Paris], The Sepages Study Group., Fondation d’entreprise MGEN pour la santé publique (FESP MGEN), Anses-PNR-EST-2015-1-022/Ademe-1594C0091, Anses-PNR-EST-2017-1-101/Ademe-1762C0021 Seventh Framework Programme, FP7: FP7/2007-206, N308333-HELIX European Research Council, ERC: N 311765-E-DOHaD Agence Nationale de la Recherche, ANR: 14-CE21-0007-01, 19-CE36-0003-01, ANR 18-CE36-005, ANR-12-PDOC-0029-01, ANR-15-IDEX, ANR-15-IDEX-02 Institut National de la Santé et de la Recherche Médicale, Inserm Fondation de France: CLI-MATHES—00081169 Commissariat Général à l'Investissement, CGI Agence Nationale de Sécurité Sanitaire de l’Alimentation, de l’Environnement et du Travail, ANSES: PNR-EST-2018-1-264 Agir pour les Maladies Chroniques, Acknowledgments: We acknowledge the role of SEPAGES cohort study group: E. Eyriey, A. Licinia, A. Vellement (Groupe Hospitalier Mutualiste, Grenoble), I. Pin, P. Hofmann, E. Hullo, C. Llerena (Grenoble University Hospital, La Tronche), X. Morin (Clinique des Cèdres, Echirolles), A. Morlot (Clinique Belledonne, Saint-Martin d’Hères), J. Lepeule, S. Lyon-Caen, C. Philippat, I. Pin, J. Quentin, V. Siroux, R. Slama (Inserm, CNRS, University Grenoble Alpes IAB research center). We thank A. Benlakhryfa, L. Borges, Y. Gioria, clinical research assistants, J. Giraud, M. Marceau, M.-P. Martin, nurses, E. Charvet, A. Putod, midwives, M. Graca, K. Gridel, C. Pelini, fieldworkers, K. Guichardet, A. Levanic, C. Martel, E. Quinteiro neuropsychologists, the sta↵ from Grenoble Center for Clinical Investigation (CIC): J.-L. Cracowski, C. Cracowski, E. Hodaj, D. Abry, N. Gonnet and A. Tournier. A warm thank you also to M. Althuser, S. Althuser, F. Camus-Chauvet, P. Dusonchet, S. Dusonchet, L. Emery, P. Fabbrizio, P. Ho↵mann, D. Marchal André, X. Morin, E. Opoix, L. Pacteau, P. Rivoire, A. Royannais, C. Tomasella, T. Tomasella, D. Tournadre, P. Viossat, E. Volpi, S. Rey, E. Warembourg and clinicians from Grenoble University Hospital for their support in the recruitment of the study volunteers. We also thank A. Buchet, S.F. Caraby, J.-N. Canonica, J. Dujourdil, E. Eyriey, P. Hofmann, M. Jeannin, A. Licina, X. Morin, A. Nicolas, and all midwives from the four maternity wards of Grenoble urban areas. We thank B. Chevolon, C. Cornes, A.S. Gauchez, D. Guergour, P. Faure, J. Arnaud for thyroid hormones assessment. We thank the team of L. Chaperod (EFS) for its implication on the immunological aspects of the project. We thank G. Uzu (IRD) and J.-L. Ja↵rezo (CNRS) for their implication on PM oxidative potential assessment. We thank F.-X. Leupert, O. Bonnet and L. Goirand for the access to the birth certificate database from the Conseil Général de l’Isère. Sépages biospecimens are stored at Grenoble University Hospital (CHU-GA) biobank (bb-0033-00069), we would like to thank the whole CRB team, led by P. Mossuz and P. Lorimier, and in particular the technicians for the huge work of biospecimens processing and pooling: W. Jayar and L. Than, as well as G. Schummer. The Internet platform for secured data collection was developed by Epiconcept Paris (E. Sevin, S. Ployart, A. Polaert). SEPAGES data are stored thanks to Inserm RE-CO-NAI platform funded by Commissariat Général à l’Investissement, with the implication of Sophie de Visme (Inserm DSI). Many thanks to M.A. Charles, RE-CO-NAI coordinator, for her support. Finally, and importantly, we would like to express our sincere thanks to participants of the SEPAGES study. The authors are grateful for the help received from Ines Taarit and Mathias Clément to update the cleaning products ingredients database., Funding: The cohort was supported by the European Research Council (consolidator grant N 311765-E-DOHaD, PI, R. Slama), by the European Community’s Seventh Framework Programme (FP7/2007-206, grant N308333-HELIX, PI, M. Vrijheid), by ANR, the French Research Agency (PAPER project ANR-12-PDOC-0029-01, PI, J. Lepeule, SHALCOH project, 14-CE21-0007-01, PI, R. Slama, GUMME project, PI, R. Slama, ETAPE ANR 18-CE36-005, PI, J. Lepeule, EDeN project 19-CE36-0003-01, SYMER project, ANR-15-IDEX-02, PI, U. Schlattner, Mobil’Air project, ANR-15-IDEX, PI, S. Mathy, supported by University Grenoble-3Alpes), by ANSES (CNAP and HYPAXE projects, PI C. Philippat, PENDORE project, PNR-EST-2018-1-264, PI, V. Siroux), by Plan Cancer (Canc’Air project, PI, P. Guénel), by Association de Recherche sur le Cancer (ARC, PI, P. Guénel), by AGIR pour les maladies chroniques (PI, R. Slama and PRENAPAR project, V. Siroux), and Fonds de Recherche pour la Santé Respiratoire (FRSR, PI, I. Pin) and by Fondation de France (CLI-MATHES—00081169, J. Lepeule). We acknowledge the support of ANSES, Inserm and AGIR pour les maladies chroniques, for SEPAGES feasibility study. The support of 'SCUSI 2017' Région Auvergne-Rhône-Alpes programme is also acknowledged. COBANET-Sepages project was support by Anses and Ademe (COBANET: Anses-PNR-EST-2015-1-022/Ademe-1594C0091, PI: N Le Moual, CRESPINET: Anses-PNR-EST-2017-1-101/Ademe-1762C0021, PI: N Le Moual). Pierre Lemire benefited from a PhD scholarship of the University of Paris-Sud/Paris-Saclay, France., The cohort was supported by the European Research Council (consolidator grant N 311765-E-DOHaD, PI, R. Slama), by the European Community?s Seventh Framework Programme (FP7/2007-206, grant N308333-HELIX, PI, M. Vrijheid), by ANR, the French Research Agency (PAPER project ANR-12-PDOC-0029-01, PI, J. Lepeule, and EDeN project 19-CE36-0003-01, SYMER project, ANR-15-IDEX-02, PI, U. Schlattner, Mobil?Air project, ANR-15-IDEX, PI, S. Mathy, supported by University Grenoble-3Alpes), by ANSES (CNAP and HYPAXE projects, PI C. Philippat, PENDORE project, PNR-EST-2018-1-264, PI, V. Siroux), by Plan Cancer (Canc?Air project, PI, P. Gu?nel), by Association de Recherche sur le Cancer (ARC, PI, P. Gu?nel), by AGIR pour les maladies chroniques (PI, R. Slama and PRENAPAR project, V. Siroux), and Fonds de Recherche pour la Sant? Respiratoire (FRSR, PI, I. Pin) and by Fondation de France (CLIMATHES?00081169, J. Lepeule). We acknowledge the support of ANSES, Inserm and AGIR pour les maladies chroniques, for SEPAGES feasibility study. The support of ?SCUSI 2017? R?gion Auvergne-Rh?ne-Alpes programme is also acknowledged. COBANET-Sepages project was support by Anses and Ademe (COBANET: Anses-PNR-EST-2015-1-022/Ademe-1594C0091, PI: N Le Moual
Subjects: medicine.medical_specialty, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], lcsh:Medicine, Smartphone application, Logistic regression, Article, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, Environmental health, Epidemiology, Odds Ratio, medicine, Humans, 030212 general & internal medicine, Association (psychology), smartphone application, Asthma, household cleaning products, business.industry, lcsh:R, Public Health, Environmental and Occupational Health, Asthma symptoms, Odds ratio, asthma, medicine.disease, 3. Good health, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Smartphone, business, Kappa, Disinfectants
Abstract: International audience; Household disinfectant and cleaning products (HDCPs) assessment is challenging in epidemiological research. We hypothesized that a newly-developed smartphone application was more objective than questionnaires in assessing HDCPs. Therefore, we aimed to compare both methods, in terms of exposure assessments and respiratory health effects estimates. The women of the SEPAGES birth cohort completed repeated validated questionnaires on HDCPs and respiratory health and used an application to report HDCPs and scan products barcodes, subsequently linked with an ingredients database. Agreements between the two methods were assessed by Kappa coefficients. Logistic regression models estimated associations of HDCP with asthma symptom score. The 101 participants (18 with asthma symptom score ≥1) scanned 617 different products (580 with available ingredients list). Slight to fair agreements for sprays, bleach and scented HDCP were observed (Kappa: 0.35, 0.25, 0.11, respectively). Strength of the associations between HDCP and asthma symptom score varied between both methods but all odds ratios (OR) were greater than one. The number of scanned products used weekly was significantly associated with the asthma symptom score (adjusted-OR [CI 95%]: 1.15 [1.00–1.32]). This study shows the importance of using novel tools in epidemiological research to objectively assess HDCP and therefore reduce exposure measurement errors.
Published: 2021
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32. Blood Metal Levels and Amyotrophic Lateral Sclerosis Risk: A Prospective Cohort

Author: Broberg, Karin E., Kippler, Maria J., Veldink, Jan Herman, Van Den Berg, Leonard H., Middleton, Lefkos T., Travis, Ruth C., Bergmann, Manuela M., Mancini, Francesca Romana, Katzke, Verena Andrea, Agudo, Antonio T., Gómez, Jesús Humberto, Rodríguez-Barranco, Miguel A., Trichopoulou, Antonia D., Vermeulen, Roel C.H., Peters, Susan, Broberg, Karin, Gallo, Valentina, Levi, Michael, Kippler, Maria, Vineis, Paolo, Veldink, Jan, Berg, Leonard, Middleton, Lefkos, Travis, Ruth, Bergmann, Manuela, Palli, Domenico, Grioni, Sara, Tumino, Rosario, Elbaz, Alexis, Vlaar, Tim, Mancini, Francesca, Kühn, Tilman, Katzke, Verena, Agudo, Antonio, Goñi, Fernando, Gómez, Jesús‐humberto, Rodríguez‐barranco, Miguel, Merino, Susana, Barricarte, Aurelio, Trichopoulou, Antonia, Jenab, Mazda, Weiderpass, Elisabete, Vermeulen, Roel, Santé publique France - French National Public Health Agency [Saint-Maurice, France], Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Institut Gustave Roussy (IGR), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), FOOD‐CT‐2005‐513943 Ministry of National Education and Religious Affairs Cancer Research UK, CRUK Wellcome Trust, WT German Cancer Research Center, DKFZ Department of Health, Australian Government Institut National de la Santé et de la Recherche Médicale, Inserm Kræftens Bekæmpelse, DCS Instituto de Salud Carlos III, ISCIII: C03/09 Stichting Diabetes Onderzoek Nederland British Heart Foundation, BHF Norges Forskningsråd QLK4CT199900927 Stroke Association European Commission, EC Deutsche Krebshilfe World Cancer Research Fund, WCRF Kreftforeningen, NCS Medical Research Council, MRC, The EPIC study is funded by a number of grants, however, no funding source had any role in the preparation of this article. The EPIC study was funded by the Europe against Cancer program of the European Commission (SANCO), Italian Association for Research on Cancer, and Italian National Research Council. In addition, the authors thank the following for their financial support: the Environmental Cancer Risk, Nutrition, and Individual Susceptibility Network of Excellence, operating within the European Union Sixth Framework Program, Priority 5: Food Quality and Safety (FOOD‐CT‐2005‐513943), European Community Fifth Framework Program (grant QLK4CT199900927), ISCIII, Red de Centros RCESP (C03/09), Deutsche Krebshilfe, Deutsches Krebsforschungszentrum, German Federal Ministry of Education and Research, Danish Cancer Society, Health Research Fund of the Spanish Ministry of Health, Spanish Regional Governments of Andalucia, Asturias, Basque Country, Murcia, and Navarra, Cancer Research UK, Medical Research Council, UK, Stroke Association, UK, British Heart Foundation, Department of Health, UK, Food Standards Agency, UK, Wellcome Trust, UK, Greek Ministry of Health, Greek Ministry of Education, Italian Association for Research on Cancer, Italian National Research Council, Dutch Ministry of Public Health, Welfare, and Sports, Netherlands Cancer Registry, LK Research Funds, Dutch Prevention Funds, Zorg Onderzoek Nederland, World Cancer Research Fund, Statistics Netherlands, Swedish Cancer, Swedish Scientific Council, Regional Government of Skåne and Västerbotten, Sweden, Norwegian Cancer Society, Research Council of Norway, French League against Cancer, INSERM, Mutuelle Generale l'Education National, and IGR. The EPIC‐Norfolk study (DOI 10.22025/2019.10.105.00004) has received funding from the Medical Research Council (MR/N003284/1 and MC‐UU_12015/1) and Cancer Research UK (C864/A14136)., and 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)
Subjects: 0301 basic medicine, Adult, Male, Risk, medicine.medical_specialty, Clinical Neurology, Gastroenterology, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, LEAD-EXPOSURE, Internal medicine, medicine, Humans, Prospective Studies, Prospective cohort study, Research Articles, POPULATION, Aged, Retrospective Studies, Science & Technology, Neurology & Neurosurgery, business.industry, Amyotrophic Lateral Sclerosis, Neurosciences, 1103 Clinical Sciences, Retrospective cohort study, Odds ratio, Environmental exposure, Environmental Exposure, Mercury, Middle Aged, 3. Good health, European Prospective Investigation into Cancer and Nutrition, 030104 developmental biology, Neurology, Cohort, Population study, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Neurosciences & Neurology, Neurology (clinical), SMOKING, 1109 Neurosciences, business, Life Sciences & Biomedicine, 030217 neurology & neurosurgery, Research Article, Cohort study
Abstract: International audience; Objective: Metals have been suggested as a risk factor for amyotrophic lateral sclerosis (ALS), but only retrospective studies are available to date. We compared metal levels in prospectively collected blood samples from ALS patients and controls, to explore whether metals are associated with ALS mortality. Methods: A nested ALS case–control study was conducted within the prospective EPIC (European Prospective Investigation into Cancer and Nutrition) cohort. Cases were identified through death certificates. We analyzed metal levels in erythrocyte samples obtained at recruitment, as a biomarker for metal exposure from any source. Arsenic, cadmium, copper, lead, manganese, mercury, selenium, and zinc concentrations were measured by inductively coupled plasma–mass spectrometry. To estimate ALS risk, we applied conditional logistic regression models. Results: The study population comprised 107 cases (65% female) and 319 controls matched for age, sex, and study center. Median time between blood collection and ALS death was 8 years (range = 1–15). Comparing the highest with the lowest tertile, cadmium (odds ratio [OR] = 2.04, 95% confidence interval [CI] = 1.08–3.87) and lead (OR = 1.89, 95% CI = 0.97–3.67) concentrations suggest associations with increased ALS risk. Zinc was associated with a decreased risk (OR = 0.50, 95% CI = 0.27–0.94). Associations for cadmium and lead remained when limiting analyses to noncurrent smokers. Interpretation: This is the first study to compare metal levels before disease onset, minimizing reverse causation. The observed associations suggest that cadmium, lead, and zinc may play a role in ALS etiology. Cadmium and lead possibly act as intermediates on the pathway from smoking to ALS. ANN NEUROL 20209999:n/a–n/a.
Published: 2021
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33. Associations between early-life food deprivation during World War II and risk of hypertension and type 2 diabetes at adulthood

Author: Guy Fagherazzi, Marie-Aline Charles, Julia Mink, Olivier Allais, Marie-Christine Boutron-Ruault, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Bodescot, Myriam, Cohortes - Etude Epidémiologique des Enfants de femmes de l'Education Nationale - - E4N2010 - ANR-10-COHO-0006 - COHO - VALID, Département d'économie (Sciences Po) (ECON), Sciences Po (Sciences Po)-Centre National de la Recherche Scientifique (CNRS), Alimentation et sciences sociales (ALISS), Université Paris-Saclay, 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), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Luxembourg Institute of Health (LIH), The E3N cohort is being carried out with the financial support of the 'Mutuelle Générale de l’Education Nationale', European Community, French League against Cancer, Gustave Roussy, and French Institute of Health and Medical Research. This present study was also supported by the French Research Agency (Agence Nationale de la Recherche) via an 'Investissement d’Avenir' grant (investment for the future grant, ANR-10-COHO-0006) that supports the E4N study and by the Strategic Research Initiative NutriPerso from the University Paris-Saclay., ANR-10-COHO-0006,E4N,Etude Epidémiologique des Enfants de femmes de l'Education Nationale(2010), 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), and Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Male, Food deprivation, World War II, Hunger, Diseases, Disease, Type 2 diabetes, First world war, 0302 clinical medicine, Medicine, 030212 general & internal medicine, Prospective Studies, Prospective cohort study, Child, 2. Zero hunger, [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Multidisciplinary, Age Factors, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, [SHS.ECO]Humanities and Social Sciences/Economics and Finance, Early life, 3. Good health, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Child, Preschool, Hypertension, Female, Adolescent, Science, 030209 endocrinology & metabolism, Affect (psychology), Article, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Humans, Adult health, business.industry, Infant, Newborn, Infant, medicine.disease, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Risk factors, Diabetes Mellitus, Type 2, Starvation, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Demography
Abstract: The Developmental Origins of Health and Disease (DOHaD) framework suggests that early-life experiences affect long-term health outcomes. We tested this hypothesis by estimating the long-run effects of exposure to World War II-related food deprivation during childhood and adolescence on the risk of suffering from hypertension and type 2 diabetes at adulthood for 90,226 women from the French prospective cohort study E3N. We found that the experience of food deprivation during early-life was associated with a higher risk of developing type 2 diabetes (+0.7%, 95% CI: 0.073–1.37%) and hypertension (+2.6%, 95% CI: 0.81–4.45%). Effects were stronger for individuals exposed at younger ages. Exposed individuals also achieved lower levels of education, slept less, and were more frequently smokers than unexposed individuals. These results are compatible with both the latency and the pathway models proposed in the DOHaD framework which theorise the association between early life exposure and adult health through both a direct link and an indirect link where changes in health determinants mediate health outcomes.
Published: 2020
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34. Heteroleptic Ruthenium(II) Complexes with Bathophenanthroline and Bathophenanthroline Disulfonate Disodium Salt as Fluorescent Dyes for In-Gel Protein Staining

Author: Olivier Poizat, Gopalakrishnan Venkatesan, Stanislav I. Bezzubov, Christian Rolando, Artem L. Gushchin, Hervé Vezin, Xavier Trivelli, Muhammad Hanif, Mohammed Kajjout, Pauline Le Faouder, Maria V. Babak, Miniaturisation pour la Synthèse, l’Analyse et la Protéomique - USR 3290 (MSAP), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Miniaturisation pour la Synthèse, l’Analyse et la Protéomique - UAR 3290 (MSAP), Institut Michel Eugène Chevreul - FR 2638 (IMEC), Université d'Artois (UA)-Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Centrale Lille Institut (CLIL), Department of Pharmacy, National University of Singapore (NUS), N. S. Kurnakov Institute of General and Inorganic Chemistry (IGIC), Russian Academy of Sciences [Moscow] (RAS), Nikolaev Institute of Inorganic Chemistry [Novosibirsk] (NIC), Siberian Branch of the Russian Academy of Sciences (SB RAS), Novosibirsk State Technical University, School of Chemical Sciences, University of Auckland [Auckland], Laboratoire Avancé de Spectroscopie pour les Intéractions la Réactivité et l'Environnement - UMR 8516 (LASIRE), Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Centrale Lille Institut (CLIL), European Community (ERDF) Region Hauts-de-France IBiSA Network Centre National de la Recherche Scientifique (CNRS) Universite de Lille European Union (EU) Ministere Francais de l'Enseignement Superieur et de la Recherche Region Hauts-de-France Universite Lille, Université d'Artois (UA)-Centrale Lille-Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Chimie du CNRS (INC)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-Université de Lille-Institut de Chimie du CNRS (INC)
Subjects: Tris, Electrophoresis, Salt (chemistry), chemistry.chemical_element, urologic and male genital diseases, 010402 general chemistry, 01 natural sciences, Ruthenium, Sypro-ruby, Inorganic Chemistry, chemistry.chemical_compound, Coordination Complexes, Cell Line, Tumor, Humans, [CHIM]Chemical Sciences, Physical and Theoretical Chemistry, Polyacrylamide Gels, ComputingMilieux_MISCELLANEOUS, Fluorescent Dyes, chemistry.chemical_classification, Electrochemiluminescence, Staining and Labeling, 010405 organic chemistry, Route, Proteins, Water, Fluorescence, 3. Good health, 0104 chemical sciences, Staining, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, Photophysics, chemistry, Electrophoresis, Polyacrylamide Gel, Bathophenanthroline disulfonate, Acids, hormones, hormone substitutes, and hormone antagonists, Phenanthrolines, Visible spectrum, Nuclear chemistry
Abstract: The in-gel detection of proteins for various proteomic experiments is commonly done with the fluorescent Ru-II tris(bathophenanthroline disulfonate) complex (Ru(BPS)(3)), which is more cost-effective compared to commercial Ru-based formulations but requires tedious procedures for its preparation and strongly acidic staining conditions. Herein, we report the synthesis and characterization of heteroleptic Ru-II complexes Ru(BPS)(2)(BP) and Ru(BPS)(BP)(2) containing bathophenanthroline (BP) and bathophenanthroline disulfonate disodium salt (BPS) in comparison with Ru(BPS)(3). It was shown by fluorescent and UV-vis measurements that novel Ru-II complexes were excitable in both UV and visible light, close to emission bands of classical lasers, which is important for successful in-gel protein detection. Novel fluorescent dyes demonstrated improved protein detection in comparison with commercially available SYPRO Ruby staining solution. In addition, unlike commonly used staining protocols, staining with Ru(BPS)(BP)(2) can be performed at nearly neutral pH, thereby reducing artificial post-translational modifications (PTMs).
Published: 2020
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35. Structure-guided design of pyridoclax derivatives based on Noxa / Mcl-1 interaction mode

Author: Christophe Denoyelle, Fabien Gautier, Peggy Suzanne, Frédéric Lopez, Jade Fogha, Laurent Poulain, Anne Sophie Voisin-Chiret, Sylvain Rault, Jana Sopkova-de Oliveira Santos, Rémi Legay, Martina De Pascale, Siham Hedir, Emilie Brotin, Marcella De Giorgi, Camille Denis, Louis-Bastien Weiswald, Bogdan A. Marekha, Philippe Juin, Ludovic Carlier, Ronan Bureau, Laetitia Ligat, Unité de recherche interdisciplinaire pour la prévention et le traitement des cancers (ANTICIPE), 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)-Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER - Institut régional du Cancer [Montpellier] (ICM), CRLCC Val d'Aurelle - Paul Lamarque, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Normandie Université (NU)-Normandie Université (NU), Stress Adaptation and Tumor Escape in breast cancer - SATE (CRCINA - Département ONCO - Equipe 8), Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers (CRCINA), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Institut de cancérologie de l'Ouest - Nantes (ICO Nantes), CRLCC Paul Papin-CRLCC René Gauducheau, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-ESPCI ParisTech-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Ecole Nationale Supérieure de Chimie de Paris- Chimie ParisTech-PSL (ENSCP)-ESPCI ParisTech-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), The Mcl-1 European and COACH-IPP European projects have been co-funded by Normandy County Council, European Union in the framework of the ERDF-ESF operational program 2014e2020. This work was also supported by the French State, INSERM, the 'Ligue Contre le Cancer' and by the 'Cancerop^ole Nord Ouest'. Acquisition of the xCELLigence real-time activity measurement system has been supported by European Commission and Comprehensive Cancer Center F. Baclesse. Part of this work was performed using computing resources of CRIANN (Normandy, France) as well as the European Community (FEDER) for the molecular modelling software. MDP was recipient of a doctoral fellowship from the 'Ligue Contre le Cancer'and SHwas recipient of a doctoral fellowship from the French 'Ministere de l’Education Superieure et de la Recherche'. Postdoctoral fellowships of LBW, MDG and BM as well as doctoral fellowships of JF and CD were supported by the Normandy County Council., CHU Caen, 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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-UNICANCER, UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), Stress Adaptation and Tumor Escape in Breast Cancer (CRCINA-ÉQUIPE 8), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Bernardo, Elizabeth
Subjects: 0301 basic medicine, Programmed cell death, Pyridines, bcl-X Protein, Regulator, [SDV.CAN]Life Sciences [q-bio]/Cancer, Tumor cells, Plasma protein binding, Molecular Dynamics Simulation, Structure-Activity Relationship, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, hemic and lymphatic diseases, Drug Discovery, Tumor Cells, Cultured, Humans, Structure–activity relationship, Cell Proliferation, Pharmacology, Cell Death, Dose-Response Relationship, Drug, Molecular Structure, Chemistry, Organic Chemistry, General Medicine, 3. Good health, Cell biology, 030104 developmental biology, Proto-Oncogene Proteins c-bcl-2, Apoptosis, Drug Design, Cancer cell, Myeloid Cell Leukemia Sequence 1 Protein, Interaction mode, Drug Screening Assays, Antitumor, Hydrophobic and Hydrophilic Interactions, Protein Binding
Abstract: International audience; Protein-protein interactions are attractive targets because they control numerous cellular processes. In oncology, apoptosis regulating Bcl-2 family proteins are of particular interest. Apoptotic cell death is controlled via PPIs between the anti-apoptotic proteins hydrophobic groove and the pro-apoptotic proteins BH3 domain. In ovarian carcinoma, it has been previously demonstrated that Bcl-x L and Mcl-1 cooperate to protect tumor cells against apoptosis. Moreover, Mcl-1 is a key regulator of cancer cell survival and is a known resistance factor to Bcl-2/Bcl-x L pharmacological inhibitors making it an attractive therapeutic target. Here, using a structure-guided design from the oligopyridine lead Pyr-idoclax based on Noxa/Mcl-1 interaction we identified a new derivative, active at lower concentration as compared to Pyridoclax. This new derivative selectively binds to the Mcl-1 hydrophobic groove and releases Bak and Bim from Mcl-1 to induce cell death and sensitize cancer cells to Bcl-2/Bcl-x L targeting strategies.
Published: 2018
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36. Determinants of 20-year non-progression to Type 2 diabetes in women at very high risk: the E3N cohort study

Author: M. C. Boutron-Ruault, Fabrice Bonnet, Gaëlle Gusto, Kalina Rajaobelina, Courtney Dow, Francesca Mancini, B. Balkau, Guy Fagherazzi, Centre de recherche en épidémiologie et santé des populations (CESP), 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), CHU Pontchaillou [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), The E3N cohort is being carried out with the financial support of the Mutuelle Générale de l'Education Nationale, the European Community, French League against Cancer, Gustave Roussy, and the French Institute of Health and Medical Research. The present study was also supported by the French Research Agency (Agence Nationale de la Recherche) via an Investissement d'Avenir (investment for the future) grant (ANR‐10‐COHO‐0006) that supports the E4N study, and the IDEX Paris Saclay (Nutriperso project)., ANR-10-COHO-0006,E4N,Etude Epidémiologique des Enfants de femmes de l'Education Nationale(2010), 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), and Université de Rennes (UR)
Subjects: Adult, medicine.medical_specialty, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, 030209 endocrinology & metabolism, Disease, Type 2 diabetes, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, Risk Factors, Surveys and Questionnaires, Internal medicine, Diabetes mellitus, Internal Medicine, medicine, Humans, 030212 general & internal medicine, Life Style, Aged, business.industry, Feeding Behavior, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Middle Aged, medicine.disease, Healthy diet, 3. Good health, Diabetes Mellitus, Type 2, Disease Progression, Female, Observational study, France, business, Risk Reduction Behavior, Very high risk, Regression tree model, Follow-Up Studies, Cohort study
Abstract: International audience; AimsTo identify the most important determinants associated with not developing Type 2 diabetes in women considered to be at very high risk.MethodsBetween 1995 and 2014, we followed 402 women from the E3N cohort study who were considered to be at very high risk of Type 2 diabetes based on the D.E.S.I.R. score. We then computed a classification and regression tree model to identify, among a large set of risk factors, the top risk factors associated with not having Type 2 diabetes at the end of the follow‐up.ResultsDuring follow‐up, 117 women (29%) were diagnosed with Type 2 diabetes, while 285 (71%) were still free of the disease in 2014. A low Western dietary pattern score was the top characteristic associated with not developing Type 2 diabetes, as only 20% of the women at very high risk in the E3N study with that characteristic developed Type 2 diabetes (compared with 29% overall). In women with a moderate or high Western dietary pattern score, the most important characteristic associated with not developing Type 2 diabetes was a high total dietary antioxidant capacity, as only 26% of these women ultimately developed Type 2 diabetes.ConclusionsWe showed that the top characteristic associated with not developing Type 2 diabetes, despite being at very high risk, was a healthy diet, characterized by limiting Western dietary habits, but with a high intake of antioxidant‐rich foods. This underscores the importance of diet in the prevention of Type 2 diabetes in people at high risk.
Published: 2018
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37. Risk factors associated with myasthenia gravis in thymoma patients: The potential role of thymic germinal centers

Author: Dominique Gossot, Elie Fadel, Sonia Berrih-Aknin, Solène Maillard, Odessa-Maud Fayet, Anthony Behin, Vincent Bondet, Audrey Mansuet-Lupo, Claire Mj. Lefeuvre, Bruno Eymard, Frédérique Truffault, Vincent Thomas de Montpréville, Marco Alifano, Pierre Validire, Darragh Duffy, Maria-Rosa Ghigna, Rozen Le Panse, Cloé A. Payet, Centre de recherche en Myologie – U974 SU-INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre chirurgical Marie Lannelongue, Université Paris-Sud - Paris 11 (UP11), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Institut Mutualiste de Montsouris (IMM), Unit of Neuromuscular Morphology [CHU Pitié-Salpêtrière], Institut de Myologie, Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), This work was supported by grants from the European Community (FIGHT-MG/HEALTH-2009-242-210), from the 'Association Française contre les Myopathies' (AFM), and from the 'Agence Nationale de la Recherche' (ANR grant number CE17001002)., We thank Mathieu Surenaud and Sophie Hüe from the immunomonitoring platform (IMRB, VRI, INSERM U955 - UPEC, France) for Bio-Plex analyses. DD thanks ImmunoQure AG for sharing the antibodies to assess IFN-α protein levels in the Simoa assay. AM-L and VM are expert members of the RYTHMIC network ('Réseau Tumeurs THYmiques et Cancer')., CCSD, Accord Elsevier, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Chirurgical Marie Lannelongue (CCML), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut de Myologie, Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-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), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Centre de Recherche en Myologie
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, Thymoma, [SDV.IMM] Life Sciences [q-bio]/Immunology, Autoimmune diseases, CD40 Ligand, Interleukin-1beta, Immunology, High endothelial venules, Gastroenterology, Interferon-gamma, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, hemic and lymphatic diseases, Paraneoplastic syndromes, Humans, Immunology and Allergy, Medicine, Receptors, Cholinergic, Receptor, Myasthenia gravis, Autoantibodies, Retrospective Studies, 030203 arthritis & rheumatology, biology, business.industry, Germinal center, Thymus Neoplasms, Middle Aged, Germinal Center, medicine.disease, 3. Good health, Thymus, Titer, 030104 developmental biology, biology.protein, Immunohistochemistry, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Antibody, business, Tertiary lymphoid structures
Abstract: International audience; Thymomas are associated with a very high risk of developing Myasthenia Gravis (MG). Our objectives were to identify histological and biological parameters to allow early diagnosis of thymoma patients susceptible to developing MG. We conducted a detailed retrospective analysis from a patient database, searching for differences between patients with thymoma-associated MG (MGT, n = 409) and thymoma without MG (TOMA, n = 111) in comparison with nonthymomatous MG patients (MG, n = 1246). We also performed multiplex and single molecule arrays to measure the serum levels of cytokines in these groups of patients and controls (n = 14-22). We identified a set of parameters associated with MG development in thymoma patients: 1) detection of anti-acetylcholine receptor (AChR) antibodies, 2) development of B1 or B2 thymoma subtypes, 3) presence of ectopic thymic germinal centers (GCs), 4) local invasiveness of thymoma, and 5) being a woman under 50 years old. Among these parameters, 58.8% of MGT patients displayed GCs with a positive correlation between the number of GCs and anti-AChR titers. By immunohistochemistry, we found thymic GCs in the adjacent tissues of thymomas encircled by high endothelial venules (HEVs) that could favor peripheral cell recruitment. We also clearly associated MG symptoms with higher IFN-γ, IL-1β and sCD40L serum levels, specifically in MGT patients compared to TOMA patients. Altogether, these analyses allowed the clear identification of histological, in particular the presence of GCs, and biological parameters that would facilitate the evaluation of the probability of the MG outcome postoperatively in thymoma patients.
Published: 2020
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38. Intracellular and in vivo evaluation of imidazo[2,1-b]thiazole-5-carboxamide anti-tuberculosis compounds

Author: Garrett C. Moraski, Nathalie Deboosere, Anne J. Lenaerts, Courtney Hastings, Alexandre Vandeputte, Priscille Brodin, Heath A. Weaver, Lisa K. Woolhiser, Marvin J. Miller, Kate L. Marshall, Department of Chemistry and Biochemistry [Bozeman, MT, États-Unis], Montana State University (MSU), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Mycobacteria Research Laboratories [Fort Collins, CO, États-Unis], Department of Microbiology, Immunology and Pathology [Fort Collins, CO, États-Unis], Colorado State University [Fort Collins] (CSU)-Colorado State University [Fort Collins] (CSU), Department of Chemistry and Biochemistry [Notre Dame, IN, États-Unis], University of Notre Dame [Indiana] (UND), This study was financially supported in part by the National Institutes of Health by grant R37AI054193 (M.J.M., G.C.M) and the National Institute of Allergy and Infectious Diseases, Contract No. HHSN272201100009I. Funding for Proteomics, Metabolomics and Mass Spectrometry Facility (at MSU) was made possible by the MJ Murdock Charitable Trust and NIH P20GM103474. Funding for the 500 NMR (at MSU) was provided by the NSF-Major Research Instrumentation program (NSF-MRI: DBI-1532078), the Murdock Charitable Trust Foundation (015066:MNL), and support from the MSU Vice-President for Research and Economic Development office. Work in Priscille Brodin’s lab was also supported from the European Community (ERC-STG INTRACELLTB n˚ 260901, MM4TB n˚260872), the Agence Nationale de la Recherche (ANR-10-EQPX-04-01, ANR-14-CE08-0017, ANR-16-CE35-0009), and the Feder (12001407 (D-AL) Equipex Imaginex BioMed) and the Région Nord Pas de Calais (convention n˚12000080)., ANR-14-CE08-0017,ANTI-TB-NANO,Une galénique ' verte ' à base de nanoparticules de cyclodextrines pour un traitement plus efficace de la tuberculose(2014), ANR-16-CE35-0009,TBemerg,Naissance d'un tueur: facteurs génétiques et adaptations métaboliques impliquées dans l'émergence des bacilles tuberculeux épidémiques(2016), ANR-10-EQPX-0004,Imaginex BioMed,Plateau de microscopie de criblage à haut débit et d'analyse à très haute résolution(2010), European Project: 260901,EC:FP7:ERC,ERC-2010-StG_20091118,INTRACELLTB(2010), European Project: 260872,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,MM4TB(2011), Bodescot, Myriam, Appel à projets générique - Une galénique ' verte ' à base de nanoparticules de cyclodextrines pour un traitement plus efficace de la tuberculose - - ANTI-TB-NANO2014 - ANR-14-CE08-0017 - Appel à projets générique - VALID, Naissance d'un tueur: facteurs génétiques et adaptations métaboliques impliquées dans l'émergence des bacilles tuberculeux épidémiques - - TBemerg2016 - ANR-16-CE35-0009 - AAPG2016 - VALID, Equipements d'excellence - Plateau de microscopie de criblage à haut débit et d'analyse à très haute résolution - - Imaginex BioMed2010 - ANR-10-EQPX-0004 - EQPX - VALID, A Chemical Genomics Approach of Intracellular Mycobacterium tuberculosis Towards Defining Specific Host Pathogen Interactions - INTRACELLTB - - EC:FP7:ERC2010-12-01 - 2015-11-30 - 260901 - VALID, More Medicines for Tuberculosis - MM4TB - - EC:FP7:HEALTH2011-02-01 - 2016-01-31 - 260872 - VALID, Centre d’Infection et d’Immunité de Lille (CIIL) - U1019 - UMR 8204 (CIIL), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), ANR-14-CE08-0017,ANTI-TB-NANO,Une galénique « verte » à base de nanoparticules de cyclodextrines pour un traitement plus efficace de la tuberculose(2014), ANR-10-EQPX-0004/10-EQPX-0004,Imaginex BioMed,Plateau de microscopie de criblage à haut débit et d'analyse à très haute résolution(2010), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)
Subjects: Bacterial Diseases, Physiology, Antitubercular Agents, Carboxamide, Pharmacology, chemistry.chemical_compound, Mice, White Blood Cells, Animal Cells, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Immune Physiology, Chlorocebus aethiops, Medicine and Health Sciences, Cytochrome P-450 Enzyme Inhibitors, ADME, Liquid Chromatography, 0303 health sciences, Multidisciplinary, Chromatographic Techniques, Imidazoles, Animal Models, 3. Good health, Body Fluids, Actinobacteria, Infectious Diseases, Blood, Experimental Organism Systems, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, medicine.symptom, Cellular Types, Anatomy, Research Article, medicine.drug_class, Immune Cells, Science, Immunology, Mouse Models, Microbial Sensitivity Tests, Research and Analysis Methods, Microbiology, Blood Plasma, 03 medical and health sciences, Model Organisms, In vivo, medicine, Potency, Animals, Humans, Tuberculosis, Animal Models of Disease, Thiazole, Vero Cells, 030304 developmental biology, Blood Cells, Bacteria, 030306 microbiology, Macrophages, Organisms, Biology and Life Sciences, Mycobacterium tuberculosis, Cell Biology, Tropical Diseases, In vitro, High Performance Liquid Chromatography, Thiazoles, Animal Models of Infection, RAW 264.7 Cells, Mechanism of action, chemistry, Microsome, Animal Studies, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Caco-2 Cells, Spleen
Abstract: International audience; The imidazo[2,1-b]thiazole-5-carboxamides (ITAs) are a promising class of anti-tuberculosis agents shown to have potent activity in vitro and to target QcrB, a key component of the mycobacterial cytochrome bcc-aa3 super complex critical for the electron transport chain. Herein we report the intracellular macrophage potency of nine diverse ITA analogs with MIC values ranging from 0.0625-2.5 μM and mono-drug resistant potency ranging from 0.0017 to 7 μM. The in vitro ADME properties (protein binding, CaCo-2, human microsomal stability and CYP450 inhibition) were determined for an outstanding compound of the series, ND-11543. ND-11543 was tolerable at >500 mg/kg in mice and at a dose of 200 mg/kg displayed good drug exposure in mice with an AUC(0-24h) >11,700 ng·hr/mL and a >24 hr half-life. Consistent with the phenotype observed with other QcrB inhibitors, compound ND-11543 showed efficacy in a chronic murine TB infection model when dosed at 200 mg/kg for 4 weeks. The efficacy was not dependent upon exposure, as pre-treatment with a known CYP450-inhibitor did not substantially improve efficacy. The ITAs are an interesting scaffold for the development of new anti-TB drugs especially in combination therapy based on their favorable properties and novel mechanism of action.
Published: 2020
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39. Selectivity via Cooperativity : Preferential Stabilization of the p65/14-3-3 Interaction with Semisynthetic Natural Products

Author: João Neves, Christian Ottmann, Sonja Srdanovic, M. Wolter, Nobuo Kato, Luc Brunsveld, Pim J. de Vink, Isabelle Landrieu, Yusuke Higuchi, Andrew J. Wilson, Eindhoven University of Technology [Eindhoven] (TU/e), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Biologie Structurale Intégrative (ERL 9002 - BSI ), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), University of Leeds, Osaka University [Osaka], University of Duisburg-Essen, This research is supported by funding from the European Union through the TASPPI project (H2020-MSCA-ITN-2015, grant number 675179) and by the LabEx (Laboratory of Excellence) DISTALZ (ANR, ANR-11-LABX-009) and through The Netherlands Organization for Scientific Research (NWO) via VICI grant 016.150.366 and via Gravity Program 024.001.035. The NMR facilities were funded by the Nord Region Council, CNRS, Institut Pasteur de Lille, the European Community (ERDF), the French Ministry of Research, and the University of Lille. We acknowledge support for the NMR facilities from TGE RMN THC (CNRS, FR-3050) and FRABio (Univ. Lille, CNRS, FR-3688). This work was supported by the EPSRC (EP/N013573/1) and The Wellcome Trust (097827/Z/11/A)., ANR-11-LABX-0009,DISTALZ,Développement de stratégies innovantes pour une approche transdisciplinaire de la maladie d'Alzheime(2011), European Project: 675179,H2020,H2020-MSCA-ITN-2015,TASPPI(2016), Université de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Chemical Biology, ICMS Core, and Universität Duisburg-Essen = University of Duisburg-Essen [Essen]
Subjects: Scaffold protein, Models, Molecular, Protein subunit, Chemie, Cooperativity, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, 010402 general chemistry, 01 natural sciences, Biochemistry, Catalysis, Article, Protein–protein interaction, chemistry.chemical_compound, Colloid and Surface Chemistry, Humans, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], ComputingMilieux_MISCELLANEOUS, Biological Products, Natural product, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Structural Biology [q-bio.BM], Drug discovery, NF-kappa B, Cooperative binding, General Chemistry, 0104 chemical sciences, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], chemistry, 14-3-3 Proteins, Biophysics, Stabilizer (chemistry), Protein Binding
Abstract: International audience; Natural compounds are an important class of potent drug molecules including some retrospectively found to act as stabilizers of protein–protein interactions (PPIs). However, the design of synthetic PPI stabilizers remains an understudied approach. To date, there are limited examples where cooperativity has been utilized to guide the optimization of a PPI stabilizer. The 14-3-3 scaffold proteins provide an excellent platform to explore PPI stabilization because these proteins mediate several hundred PPIs, and a class of natural compounds, the fusicoccanes, are known to stabilize a subset of 14-3-3 protein interactions. 14-3-3 has been reported to negatively regulate the p65 subunit of the NF-κB transcription factor, which qualifies this protein complex as a potential target for drug discovery to control cell proliferation. Here, we report the high-resolution crystal structures of two 14-3-3 binding motifs of p65 in complex with 14-3-3. A semisynthetic natural product derivative, DP-005, binds to an interface pocket of the p65/14-3-3 complex and concomitantly stabilizes it. Cooperativity analyses of this interaction, and other disease relevant 14-3-3-PPIs, demonstrated selectivity of DP-005 for the p65/14-3-3 complex. The adaptation of a cooperative binding model provided a general approach to characterize stabilization and to assay for selectivity of PPI stabilizers.
Published: 2020
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40. Assessing the representation of phonological rules by a production study of non-words in Coratino

Author: Jean-Luc Schwartz, Mirko Grimaldi, Paolo Lorusso, Silvain Gerber, Jonathan Bucci, BCL, équipe Dialectologie et Linguistique formelle, Bases, Corpus, Langage (UMR 7320 - UCA / CNRS) (BCL), Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Centro di Ricerca Interdisciplinare sul Linguaggio (CRIL), Università degli studi di Lecce, GIPSA-Services (GIPSA-Services), Grenoble Images Parole Signal Automatique (GIPSA-lab ), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Centro de Ricerca Interdisciplinare sul Linguagio (CRIL), Università del Salento [Lecce], GIPSA - Perception, Contrôle, Multimodalité et Dynamiques de la parole (GIPSA-PCMD), Département Parole et Cognition (GIPSA-DPC), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-Institut Polytechnique de Grenoble - Grenoble Institute of Technology-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Grenoble Images Parole Signal Automatique (GIPSA-lab ), This work was supported by the European Research Council under the 7th European Community Program (FP7/2007–2013 Grant Agreement No. 339152 – 'Speech Unit(e)s')., European Project: 339152,EC:FP7:ERC,ERC-2013-ADG,SPEECH UNIT(E)S(2014), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Bucci, Jonathan, Lorusso, Paolo, Gerber, Silvain, Grimaldi, Milko Antonino, and Schwartz, Jean-Luc
Subjects: Fonologia, Male, Consonant, 050101 languages & linguistics, Linguistics and Language, Speech production, internal grammar, Acoustics and Ultrasonics, speech production, Non-words, Vowel reduction, Corpus, Language and Linguistics, Production experiment, 030507 speech-language pathology & audiology, 03 medical and health sciences, Italian dialect, [SCCO]Cognitive science, cognitive representations, Phonetics, Humans, Speech, 0501 psychology and cognitive sciences, Phonological rules, phonetics, dialect variation, Language, Mathematics, Dialects, rules, 05 social sciences, Phonology, Langage - Vowel reduction, Dialetti, Distinctive feature, [SCCO.LING]Cognitive science/Linguistics, Linguistics, Laboratoire BCL: Bases, phonology, Esperimento di produzione, Riduzione vocalica, vowel reduction, Italy, Phonological rule, Mid vowel, Female, nonwords, 0305 other medical science, Articulation (phonetics), non-words
Abstract: Phonological regularities in a given language can be described as a set of formal rules applied on logical expressions (e.g. the value of a distinctive feature) or rather as distributional properties emerging from the phonetic substance. An indirect way to assess how phonology is represented in a speaker’s brain consists in testing how phonological regularities are transferred to non-words. This is this objective of this study, focusing on Coratino, a dialect from southern Italy spoken in the Apulia region. In Coratino, a complex process of vowel reduction operates, characterized by four major properties: (1) /i e ɛ u o ɔ/ are reduced in unstressed position while /a/ is maintained; (2) all initial vowels are maintained, even unstressed; (3) unstressed vowels /i e ɛ u o ɔ/ are protected against reduction when they are adjacent to a consonant that shares articulation (labiality and velarity for /u o ɔ/ and palatality for /i e ɛ/); (4) when they are reduced, high vowels are reduced to /ɨ/ and mid vowels to /ə/. A production experiment was carried out on 19 speakers of Coratino to test whether these properties were displayed with non-words. The production data display a complex pattern, in which each of the four properties do transfer to non-words, though in a different way, which seems to imply both either explicit/formal rules (for maintenance in initial position and the reduction to two targets) and distributional properties transferred in a statistical way to non-words (for consonantal protection and robustness of /a/). Furthermore, the speakers appear as largely variable in this task. Altogether, this suggests that both formal rules and distributional principles participate to the encoding of Coratino phonology in the speakers’ brain.
Published: 2019
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41. Joint effects of intensity and duration of cigarette smoking on the risk of head and neck cancer: A bivariate spline model approach

Author: Philip Lazarus, Claire M. Healy, Richard B. Hayes, Rolando Herrero, Elaine M. Smith, Stefania Boccia, Leonardo F. Boaventura Rios, Paolo Boffetta, Dana Mates, Jerry Polesel, Marta Vilensky, Jose P. Zevallos, Diego Serraino, Gypsyamber D'Souza, Joshua E. Muscat, Kirsten B. Moysich, Yuan Chin Amy Lee, Mark P. Purdue, Carlo La Vecchia, Heribert Ramroth, Thomas L. Vaughan, Peter Thomson, Karl T. Kelsey, Nicola Torelli, Wolfgang Ahrens, Hermann Brenner, Lorenzo Richiardi, Victor Wünsch-Filho, Kristina Kjærheim, Beata Swiatkowska, Keitaro Matsuo, Fabio Levi, Erich M. Sturgis, Eva Negri, Lorenzo Simonato, Danièle Luce, Guo Pei Yu, Chu Chen, Pagona Lagiou, Silvia Franceschi, Andrew F. Olshan, Alexander W. Daudt, Antonio Agudo, Maria Paula Curado, Peter Rudnai, Tatiana V. Macfarlane, Zuo-Feng Zhang, Mia Hashibe, Paul Brennan, Tatiana Natasha Toporcov, Stimson P. Schantz, Maura L. Gillison, Isabelle Stücker, Tongzhang Zheng, Shu Chun Chuang, Oxana Shangina, Eleonora Fabianova, Hal Morgenstern, David I. Conway, Valeria Edefonti, Cristina Bosetti, Ariana Znaor, Leticia Fernandez, Michael D. McClean, Luigino Dal Maso, Neil D. Gross, Stephen M. Schwartz, Ivana Holcatova, Guojun Li, Ana M. B. Menezes, Francesco Pauli, Gioia Di Credico, Deborah M. Winn, Rosalina Jorge Koifman, Gwenn Menvielle, Gabriella Cadoni, Werner Garavello, Jolanda Lissowska, Università degli Studi di Milano [Milano] (UNIMI), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), University of Glasgow, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), TW001500, National Institutes of Health, P30ES010126, National Institute of Environmental Health Sciences, Italian Ministry of Education, Università degli Studi di Milano, Jonsson Comprehensive Cancer Center, International Union Against Cancer, Fondo para la Investigacion Cientifica y Tecnologica Argentina, Institut Hospital del Mar d’Investigacions Mediquès (IMIM), Fundação de Amparo à Pesquisa no Estado de São Paulo, Spanish Government, European Community, Ministry of Science, Research and Arts Baden-Wurttemberg, German Ministry of Education and Research, Scientific Research grant from the Ministry of Education, Science, Sports, Culture and Technology of Japan, Labor and Welfare of Japan, Italian Foundation for Cancer Research, Di Credico G., Edefonti V., Polesel J., Pauli F., Torelli N., Serraino D., Negri E., Luce D., Stucker I., Matsuo K., Brennan P., Vilensky M., Fernandez L., Curado M.P., Menezes A., Daudt A.W., Koifman R., Wunsch-Filho V., Holcatova I., Ahrens W., Lagiou P., Simonato L., Richiardi L., Healy C., Kjaerheim K., Conway D.I., Macfarlane T.V., Thomson P., Agudo A., Znaor A., Boaventura Rios L.F., Toporcov T.N., Franceschi S., Herrero R., Muscat J., Olshan A.F., Zevallos J.P., La Vecchia C., Winn D.M., Sturgis E.M., Li G., Fabianova E., Lissowska J., Mates D., Rudnai P., Shangina O., Swiatkowska B., Moysich K., Zhang Z.-F., Morgenstern H., Levi F., Smith E., Lazarus P., Bosetti C., Garavello W., Kelsey K., McClean M., Ramroth H., Chen C., Schwartz S.M., Vaughan T.L., Zheng T., Menvielle G., Boccia S., Cadoni G., Hayes R.B., Purdue M., Gillison M., Schantz S., Yu G.-P., Brenner H., D'Souza G., Gross N.D., Chuang S.-C., Boffetta P., Hashibe M., Lee Y.-C.A., Dal Maso L., Di Credico, G, Edefonti, V, Polesel, J, Pauli, F, Torelli, N, Serraino, D, Negri, E, Luce, D, Stucker, I, Matsuo, K, Brennan, P, Vilensky, M, Fernandez, L, Curado, M, Menezes, A, Daudt, A, Koifman, R, Wunsch-Filho, V, Holcatova, I, Ahrens, W, Lagiou, P, Simonato, L, Richiardi, L, Healy, C, Kjaerheim, K, Conway, D, Macfarlane, T, Thomson, P, Agudo, A, Znaor, A, Boaventura Rios, L, Toporcov, T, Franceschi, S, Herrero, R, Muscat, J, Olshan, A, Zevallos, J, La Vecchia, C, Winn, D, Sturgis, E, Li, G, Fabianova, E, Lissowska, J, Mates, D, Rudnai, P, Shangina, O, Swiatkowska, B, Moysich, K, Zhang, Z, Morgenstern, H, Levi, F, Smith, E, Lazarus, P, Bosetti, C, Garavello, W, Kelsey, K, Mcclean, M, Ramroth, H, Chen, C, Schwartz, S, Vaughan, T, Zheng, T, Menvielle, G, Boccia, S, Cadoni, G, Hayes, R, Purdue, M, Gillison, M, Schantz, S, Yu, G, Brenner, H, D'Souza, G, Gross, N, Chuang, S, Boffetta, P, Hashibe, M, Lee, Y, Dal Maso, L, Di Credico, Gioia, Edefonti, Valeria, Polesel, Jerry, Pauli, Francesco, Torelli, Nicola, Serraino, Diego, Negri, Eva, Luce, Daniele, Stucker, Isabelle, Matsuo, Keitaro, Brennan, Paul, Vilensky, Marta, Fernandez, Leticia, Curado, Maria Paula, Menezes, Ana, Daudt, Alexander W., Koifman, Rosalina, Wunsch-Filho, Victor, Holcatova, Ivana, Ahrens, Wolfgang, Lagiou, Pagona, Simonato, Lorenzo, Richiardi, Lorenzo, Healy, Claire, Kjaerheim, Kristina, Conway, David I., Macfarlane, Tatiana V., Thomson, Peter, Agudo, Antonio, Znaor, Ariana, Boaventura Rios, Leonardo F., Toporcov, Tatiana N., Franceschi, Silvia, Herrero, Rolando, Muscat, Joshua, Olshan, Andrew F., Zevallos, Jose P., La Vecchia, Carlo, Winn, Deborah M., Sturgis, Erich M., Li, Guojun, Fabianova, Eleonora, Lissowska, Jolanda, Mates, Dana, Rudnai, Peter, Shangina, Oxana, Swiatkowska, Beata, Moysich, Kirsten, Zhang, Zuo-Feng, Morgenstern, Hal, Levi, Fabio, Smith, Elaine, Lazarus, Philip, Bosetti, Cristina, Garavello, Werner, Kelsey, Karl, Mcclean, Michael, Ramroth, Heribert, Chen, Chu, Schwartz, Stephen M., Vaughan, Thomas L., Zheng, Tongzhang, Menvielle, Gwenn, Boccia, Stefania, Cadoni, Gabriella, Hayes, Richard B., Purdue, Mark, Gillison, Maura, Schantz, Stimson, Yu, Guo-Pei, Brenner, Hermann, D'Souza, Gypsyamber, Gross, Neil D., Chuang, Shu-Chun, Boffetta, Paolo, Hashibe, Mia, Lee, Yuan-Chin Amy, Dal Maso, Luigino, Università degli Studi di Milano = University of Milan (UNIMI), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), 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), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)
Subjects: Male, Oral cavity and pharyngeal cancers, Cancer Research, Bivariate spline model, medicine.medical_treatment, Logistic regression, Substance Misuse, 0302 clinical medicine, Risk Factors, Laryngeal cancer, 80 and over, 2.2 Factors relating to the physical environment, Aetiology, 030223 otorhinolaryngology, Head and neck cancer, Cancer, Aged, 80 and over, Confounding, Middle Aged, 3. Good health, Oncology, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Bivariate spline models, Cigarette smoking duration, Cigarette smoking intensity, Public Health and Health Services, Female, Oral Surgery, Adult, INHANCE, Oncology and Carcinogenesis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Bivariate analysis, Cigarette Smoking, 03 medical and health sciences, Rare Diseases, Clinical Research, Tobacco, medicine, Humans, Oncology & Carcinogenesis, Dental/Oral and Craniofacial Disease, Aged, Settore MED/06 - ONCOLOGIA MEDICA, Tobacco Smoke and Health, business.industry, Prevention, Case-control study, Odds ratio, medicine.disease, Former Smoker, Good Health and Well Being, Case-Control Studies, Dentistry, Smoking cessation, business, Demography
Abstract: Objectives: \ud This study aimed at re-evaluating the strength and shape of the dose-response relationship between the combined (or joint) effect of intensity and duration of cigarette smoking and the risk of head and neck cancer (HNC). We explored this issue considering bivariate spline models, where smoking intensity and duration were treated as interacting continuous exposures.\ud \ud Materials and Methods: \ud We pooled individual-level data from 33 case-control studies (18,260 HNC cases and 29,844 controls) participating in the International Head and Neck Cancer Epidemiology (INHANCE) consortium. In bivariate regression spline models, exposures to cigarette smoking intensity and duration (compared with never smokers) were modeled as a linear piecewise function within a logistic regression also including potential confounders. We jointly estimated the optimal knot locations and regression parameters within the Bayesian framework.\ud \ud Results: \ud For oral-cavity/pharyngeal (OCP) cancers, an odds ratio (OR) >5 was reached after 30 years in current smokers of ∼20 or more cigarettes/day. Patterns of OCP cancer risk in current smokers differed across strata of alcohol intensity. For laryngeal cancer, ORs >20 were found for current smokers of ≥20 cigarettes/day for ≥30 years. In former smokers who quit ≥10 years ago, the ORs were approximately halved for OCP cancers, and ∼1/3 for laryngeal cancer, as compared to the same levels of intensity and duration in current smokers.\ud \ud Conclusion: \ud Referring to bivariate spline models, this study better quantified the joint effect of intensity and duration of cigarette smoking on HNC risk, further stressing the need of smoking cessation policies.
Published: 2019
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42. Determinants of fractional exhaled nitric oxide in healthy men and women from the European Community Respiratory Health Survey III

Author: Roberto Bono, Mario Olivieri, Torben Sigsgaard, Anna C. Olin, A. Malinovschi, Deborah Jarvis, Isabelle Pin, Bénédicte Leynaert, Simone Accordini, Joachim Heinric, Jan Paul Zock, Elisabet Nerpin, Angelo Corsico, Bertil Forsberg, Christer Janson, Alessandro Marcon, Lucia Cazzoletti, Pascal Demoly, Joost Weyler, Rune Nielsen, Thorainn Gislason, Diogenes S. Ferreira, Rain Jõgi, Ane Johannessen, Dennis Nowak, Uppsala University Hospital, University of Verona (UNIVR), Landspitali National University Hospital of Iceland, Department of Swedish [Gothenburg], University of Gothenburg (GU), Haukeland University Hospital, University of Bergen (UiB), Monash University [Melbourne], Universidade Federal do Parana [Curitiba] (UFPR), Universidade Federal do Paraná (UFPR), Department of Diagnostics and Public Health [Verona] (UNIVR | DDSP), Centre Hospitalier Universitaire [Grenoble] (CHU), University of Pavia, Hôpital Arnaud de Villeneuve [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Universiteit Antwerpen [Antwerpen], Ludwig Maximilian University [Munich] (LMU), University of Tartu, Umeå University, Universitat Pompeu Fabra [Barcelona] (UPF), Centro de Investigación Biomédica en Red Enfermedades Respiratorias (CIBERES), Aarhus University Hospital, Ludwig-Maximilians-Universität München (LMU), Helmholtz-Zentrum München (HZM), Melbourne School of Population and Global Health [Melbourne], University of Melbourne, University of Turin, Physiopathologie et Epidémiologie des Maladies Respiratoires (PHERE (UMR_S_1152 / U1152)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, European Community Resp Hlth Surve, Università degli studi di Verona = University of Verona (UNIVR), Università degli Studi di Pavia = University of Pavia (UNIPV), Universiteit Antwerpen = University of Antwerpen [Antwerpen], Helmholtz Zentrum München = German Research Center for Environmental Health, Università degli studi di Torino = University of Turin (UNITO), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), and Salvy-Córdoba, Nathalie
Subjects: Male, 0301 basic medicine, Fractional Exhaled Nitric Oxide, Healthy Population, Ige Sensitization, Smoking, [SDV.MHEP.PSR]Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, 0302 clinical medicine, Surveys and Questionnaires, Immunology and Allergy, Medicine, [SDV.IMM.ALL]Life Sciences [q-bio]/Immunology/Allergology, Ige sensitization, Healthy population, Middle Aged, respiratory system, 3. Good health, fractional exhaled nitric oxide, Breath Tests, Exhalation, Biomarker (medicine), Female, FENO, [SDV.IMM.ALL] Life Sciences [q-bio]/Immunology/Allergology, Adult, medicine.medical_specialty, European community, Immunology, IgE sensitization, Nitric Oxide, smoking, 03 medical and health sciences, Internal medicine, Humans, European Union, Respiratory health, FENO, healthy population, IgE sensitization, smoking, Aged, Asthma, business.industry, Fractional exhaled nitric oxide, medicine.disease, Health Surveys, respiratory tract diseases, Cross-Sectional Studies, 030104 developmental biology, 030228 respiratory system, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Exhaled nitric oxide, [SDV.MHEP.PSR] Life Sciences [q-bio]/Human health and pathology/Pulmonology and respiratory tract, healthy population, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Human medicine, business, Follow-Up Studies
Abstract: Introduction: The fractional exhaled nitric oxide (FENO) is a marker for type 2 inflammation used in diagnostics and management of asthma. In order to use FENO as a reliable biomarker, it is important to investigate factors that influence FENO in healthy individuals. Men have higher levels of FENO than women, but it is unclear whether determinants of FENO differ by sex. Objective: To identify determinants of FENO in men and women without lung diseases. Method: Fractional exhaled nitric oxide was validly measured in 3881 healthy subjects that had answered the main questionnaire of the European Community Respiratory Health Survey III without airways or lung disease. Results: Exhaled NO levels were 21.3% higher in men compared with women P ENO than subjects in the lowest age quartile (39.7-48.3 years) P = 0.02. Women in the two highest age quartiles (54.6-60.2 and 60.3-67.6 years) had 15.4 ppb (14.7, 16.2), P = 0.03 and 16.4 ppb (15.6, 17.1), P = ENO, compared with the lowest age quartile. Height was related to 8% higher FENO level in men (P ENO levels in women (P = 0.008). Men who smoked had 37% lower FENO levels and women had 30% lower levels compared with never-smokers (P ENO levels compared with non-sensitized subjects 26% and 29%, P ENO started increasing at lower age in women than in men, suggesting that interpretation of FENO levels in adults aged over 50 years should take into account age and sex.
Published: 2019
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43. Muscle strength field-based tests to identify European adolescents at risk of metabolic syndrome: The HELENA study

Author: Ángel Gutiérrez, José Castro-Piñero, Angela Polito, Marcela González-Gross, Francisco B. Ortega, Yannis Manios, Luis A. Moreno, Azahara I. Rupérez, Ascensión Marcos, Enrique G. Artero, Jérémy Vanhelst, Kurt Widhalm, Kelly R. Laurson, Idoia Labayen, Jonatan R. Ruiz, Mahmoud Zaqout, University of Cadiz, School of Kinesiology and Recreation [Illinois State University], Illinois State University, Universidad de Almería (UAL), Universidad de Granada (UGR), Karolinska Institutet [Stockholm], Universidad Pública de Navarra [Espagne] = Public University of Navarra (UPNA), University of Zaragoza - Universidad de Zaragoza [Zaragoza], Universiteit Gent = Ghent University [Belgium] (UGENT), Harokopio University of Athens, Lille Inflammation Research International Center - U 995 (LIRIC), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Spanish National Research Council (CSIC), Istituto Nazionale di Ricerca per gli Alimenti e la Nutrizione, Universidad Politécnica de Madrid (UPM), Instituto de Salud Carlos III [Madrid] (ISC), Medizinische Universität Wien = Medical University of Vienna, The HELENA project was supported by the European Community Sixth RTD Framework Programme (contract FOOD-CT-2005-007034). The data for this study was gathered under the aegis of the HELENA project, and further analysis was additionally supported by the Spanish Ministry of Economy and Competitiveness (grants RYC-201416390), the Spanish Ministry of Health: Maternal, Child Health and Development Network (grant RD16/0022), the Fondo Europeo de Desarrollo Regional (MICINN-FEDER) and by the University of Granada, Plan Propio de Investigación 2016, Excellence actions: Units of Excellence, Unit of Excellence on Exercise and Health (UCEES) and Plan Propio de Investigación 2018 - Programa Contratos-Puente, and the Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades (FEDER, ref. SOMM17/6107/UGR)., We thank the adolescents who participated in the study and their parents and teachers for their collaboration. We also acknowledge the members involved in fieldwork for their efforts and the HELENA study group., Ministerio de Educación (España), Ministerio de Ciencia e Innovación (España), Universidad de Granada, European Commission, Junta de Andalucía, Ministerio de Economía y Competitividad (España), Université de Lille, Inserm, CHU Lille, Universidad de Cádiz [UCA], Universidad de Almería [UAL], Universidad Pública de Navarra [Espagne] = Public University of Navarra [UPNA], Universiteit Gent = Ghent University [UGENT], Lille Inflammation Research International Center - U 995 [LIRIC], Spanish National Research Council [CSIC], Consiglio per la Ricerca in Agricoltura e l’analisi dell’economia agraria = Council for Agricultural Research and Economics [CREA], Instituto de Salud Carlos III [Madrid] [ISC], Universidad de Granada = University of Granada [UGR], Universidad de Granada = University of Granada (UGR), Universiteit Gent = Ghent University (UGENT), Institut Pasteur de Lille, and Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: Male, [SDV]Life Sciences [q-bio], Adolescents, MESH: Risk Assessment, Fasting insulin, 0302 clinical medicine, Risk Factors, MESH: Risk Factors, Prevalence, Orthopedics and Sports Medicine, 030212 general & internal medicine, Cardiometabolic risk, Metabolic Syndrome, MESH: Metabolic Syndrome/epidemiology, Anthropometry, Hand Strength, Standing long jump, 3. Good health, Europe, Female, medicine.medical_specialty, Adolescent, Cross-Sectional Studies, Humans, Muscle Strength, Risk Assessment, Muscle fitness, Physical Therapy, Sports Therapy and Rehabilitation, 03 medical and health sciences, MESH: Cross-Sectional Studies, MESH: Anthropometry, Internal medicine, medicine, Field based, MESH: Prevalence, MESH: Hand Strength/physiology, MESH: Adolescent, MESH: Humans, Receiver operating characteristic, business.industry, Cardiorespiratory fitness, 030229 sport sciences, medicine.disease, MESH: Male, MESH: Europe/epidemiology, Muscle strength, MESH: Muscle Strength/physiology, Metabolic syndrome, business, MESH: Female
Abstract: [Objectives]: To determine whether handgrip strength (HG) and/or standing long jump (SLJ) are capable of detecting risk of metabolic syndrome (MetS) in European adolescents, and to identify age- and sex-specific cut points for these tests. [Design]: Cross-sectional study. [Methods]: Participants included 969 (aged 12.5–17.5 years old) adolescents from 9 European countries (n = 520 girls). Absolute and relative HG and SLJ tests were used to assess upper and lower muscle strength, respectively. MetS status was determined using the age- and sex-specific cut points proposed by Jolliffe and Janssen's, Additionally, we computed a continuous cardiometabolic risk index with the average z-score of four cardiometabolic risk factors: Wait circumference, mean arterial pressure, triglycerides/high-density lipoprotein cholesterol, and fasting insulin. [Results]: The prevalence of MetS was 3.1% in European adolescents. Relative HG and absolute SLJ were the best tests for detecting the presence of MetS (Area under the receiver operating characteristic (AUC) = 0.799, 95%CI:0.773–0.824; and AUC = 0.695 95%CI:0.665–0.724), respectively) and elevated cardiometabolic risk index (AUC = 0.873, 95%CI:0.838–0.902; and AUC = 0.728 95%CI:0.698–0.756), respectively) and, regardless of cardiorespiratory fitness. We provide age- and sex-specific cut points of upper and lower muscle strength for European adolescents to identify the presence of MetS and elevated cardiometabolic risk index. [Conclusions]: The proposed health-related cut points could be used as a starting point to define health-related levels of upper and lower muscle strength in adolescents. Likewise, the diagnostic statistics provided herein can be used to offer feedback to adolescents, parents, and education and health professionals about what it means to meet or fail test standards., The HELENA project was supported by the European Community Sixth RTD Framework Programme (contract FOOD-CT-2005-007034). The data for this study was gathered under the aegis of the HELENA project, and further analysis was additionally supported by the Spanish Ministry of Economy and Competitiveness (grants RYC-201416390), the Spanish Ministry of Health: Maternal, Child Health and Development Network (grant RD16/0022), the Fondo Europeo de Desarrollo Regional (MICINN-FEDER) and by the University of Granada, Plan Propio de Investigación 2016, Excellence actions: Units of Excellence; Unit of Excellence on Exercise and Health (UCEES) and Plan Propio de Investigación 2018 - Programa Contratos-Puente, and the Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades (FEDER, ref. SOMM17/6107/UGR).
Published: 2019
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44. Intrinsic Antibacterial Activity of Nanoparticles Made of β-Cyclodextrins Potentiates Their Effect as Drug Nanocarriers against Tuberculosis

Author: Giuseppina Salzano, Alain R. Baulard, Eric Muraille, Valerie Giannini, Aurore Demars, Camille Locht, Arnaud Machelart, Sophie Simar, Priscille Brodin, Samuel Jouny, Fabrice Nesslany, Anne Sophie Debrie, Elisabetta Pancani, Smaïl Talahari, Imène Belhaouane, Xue Li, Roland Brosch, Ruxandra Gref, Laleh Majlessi, Baptiste Villemagne, Carine Rouanet, Marion Flipo, Eik Hoffmann, Benoit Deprez, Mario Menendez-Miranda, Nathalie Deboosere, Nicolas Willand, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Institut des Sciences Moléculaires d'Orsay (ISMO), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Université de Namur [Namur] (UNamur), Impact de l'environnement chimique sur la santé humaine - ULR 4483 (IMPECS), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Réseau International des Instituts Pasteur (RIIP), Pathogénomique mycobactérienne intégrée - Integrated Mycobacterial Pathogenomics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Médicaments et molécules pour agir sur les Systèmes Vivants - U 1177 (M2SV), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Université libre de Bruxelles (ULB), Financial support for this work was provided by the European Community (CycloNHit no. 608407, ERC-STG INTRACELLTB no. 260901, MM4TB no. 260872), the Agence Nationale de la Recherche (ANR-10-EQPX-04-01, ANR-14-CE08-0017, ANR-16-CE35-0009), the Projet Transversal de l’Institut Pasteur (PTR441, PTR22-16), the EMBO Young Investigator Program, the Feder (12001407 (D-AL) Equipex Imaginex BioMed), the Région Hauts-de-France (convention no. 12000080), and the Fondation pour la Recherche Medicale (SPF20170938709). This work was supported by a public grant overseen by the French National Research Agency (ANR) as part of the 'Investissements d’Avenir' program (Labex NanoSaclay, ANR-10-LABX-0035)., We gratefully acknowledge F. Leroux, H. Bauderlique, O. R. Song, I. Ricard, and A. Vandeputte for technical assistance and helpful discussions. We also acknowledge R. Prath, N. Vandenabeele, and D. Legrand for technical assistance in BSL3 and animal facilities. We are grateful to Roquette for kindly providing us with a sample of β-cyclodextrin. We acknowledge the PICT-IBiSA and F. Lafont from BiCEL for providing access to microscopy equipment., ANR-11-IDEX-0003,IPS,Idex Paris-Saclay(2011), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
Subjects: Drug, Male, Tuberculosis, medicine.drug_class, media_common.quotation_subject, Antibiotics, Antitubercular Agents, General Physics and Astronomy, 02 engineering and technology, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Pharmacology, 010402 general chemistry, 01 natural sciences, Article, host-directed therapy, Mycobacterium tuberculosis, Drug Delivery Systems, antibacterial activity, Macrophages, Alveolar, medicine, Animals, Humans, General Materials Science, media_common, Drug Carriers, Mice, Inbred BALB C, cyclodextrins, biology, Chemistry, beta-Cyclodextrins, General Engineering, Sciences bio-médicales et agricoles, 021001 nanoscience & nanotechnology, medicine.disease, biology.organism_classification, 3. Good health, 0104 chemical sciences, Mice, Inbred C57BL, drug nanocarrier, tuberculosis, Toxicity, Nanoparticles, Female, Nanocarriers, 0210 nano-technology, Drug carrier, Antibacterial activity
Abstract: Multi-drug-resistant tuberculosis (TB) is a major public health problem, concerning about half a million cases each year. Patients hardly adhere to the current strict treatment consisting of more than 10 000 tablets over a 2-year period. There is a clear need for efficient and better formulated medications. We have previously shown that nanoparticles made of cross-linked poly-β-cyclodextrins (pβCD) are efficient vehicles for pulmonary delivery of powerful combinations of anti-TB drugs. Here, we report that in addition to being efficient drug carriers, pβCD nanoparticles are endowed with intrinsic antibacterial properties. Empty pβCD nanoparticles are able to impair Mycobacterium tuberculosis (Mtb) establishment after pulmonary administration in mice. pβCD hamper colonization of macrophages by Mtb by interfering with lipid rafts, without inducing toxicity. Moreover, pβCD provoke macrophage apoptosis, leading to depletion of infected cells, thus creating a lung microenvironment detrimental to Mtb persistence. Taken together, our results suggest that pβCD nanoparticles loaded or not with antibiotics have an antibacterial action on their own and could be used as a carrier in drug regimen formulations effective against TB., SCOPUS: ar.j, info:eu-repo/semantics/published
Published: 2019
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45. Predictive Value of Cellular Accumulation of Hydrophobic Bile Acids As a Marker of Cholestatic Drug Potential

Author: Audrey Burban, Lydie Humbert, Thibaut Eguether, Christiane Guguen-Guillouzo, Ahmad Sharanek, André Guillouzo, Dominique Rainteau, Nutrition, Métabolismes et Cancer (NuMeCan), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire des biomolécules (LBM UMR 7203), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Département de Chimie - ENS Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), 115336, European Community through the Innovative Medicines Initiative Joint Undertaking, FP7/2007–2013, European Union’s Seventh Framework Programme, MIP-DILI, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Département de Chimie - ENS Paris, École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), and Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Drug, Lithocholic acid, Drug-Related Side Effects and Adverse Reactions, amidation, media_common.quotation_subject, education, Drug Evaluation, Preclinical, Toxicology, Bone canaliculus, Tandem mass spectrometry, Bile Acids and Salts, 03 medical and health sciences, chemistry.chemical_compound, HepaRG hepatocytes, 0302 clinical medicine, Sulfation, Cholestasis, Predictive Value of Tests, Chenodeoxycholic acid, medicine, Humans, cholestatic drugs, media_common, Chemistry, Deoxycholic acid, sulfation, noncholestatic drugs, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, medicine.disease, 030104 developmental biology, Biochemistry, lithocholic acid, Liver, Pharmaceutical Preparations, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Hepatocytes, hydrophobic bile acids, Hydrophobic and Hydrophilic Interactions, 030217 neurology & neurosurgery, Biomarkers
Abstract: Drug-induced cholestasis is mostly intrahepatic and characterized by alterations of bile canaliculi dynamics and morphology as well as accumulation of bile acids (BAs) in hepatocytes. However, little information exists on first changes in BA content and profile induced by cholestatic drugs in human liver. In this study, we aimed to analyze the effects of a large set of cholestatic and noncholestatic drugs in presence of physiological serum concentrations and 60-fold higher levels of 9 main BAs on cellular accumulation of BAs using HepaRG hepatocytes. BAs were measured in cell layers (cells + bile canaliculi) and culture media using high-pressure liquid chromatography coupled with tandem mass spectrometry after 24 h-treatment. Comparable changes in total and individual BA levels were observed in cell layers and media from control and noncholestatic drug-treated cultures: unconjugated BAs were actively amidated and lithocholic acid (LCA) was entirely sulfated. In contrast, cellular accumulation of LCA and in addition, of the 2 other hydrophobic BAs, chenodeoxycholic acid and deoxycholic acid, was evidenced only with cholestatic compounds in presence of BA mixtures at normal and 60-fold serum levels, respectively, suggesting that LCA was the first BA to accumulate. Cellular accumulation of hydrophobic BAs was associated with inhibition of their amidation and for LCA, its sulfation. In conclusion, these results demonstrated that cellular accumulation of unconjugated hydrophobic BAs can be caused by various cholestatic drugs in human hepatocytes and suggest that their cellular detection, especially that of LCA, could represent a new strategy for evaluation of cholestatic potential of drugs and other chemicals.
Published: 2019
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46. Inhibiting Acetylcholinesterase to Activate Pleiotropic Prodrugs with Therapeutic Interest in Alzheimer’s Disease

Author: Patrick Dallemagne, François-Xavier Toublet, Julien Lalut, Marc Since, Bérénice Hatat, Cédric Lecoutey, Thomas Freret, Jana Sopkova-de Oliveira Santos, Christophe Rochais, Audrey Davis, Sophie Corvaisier, Sylvie Claeysen, Michel Boulouard, Centre d'Etudes et de Recherche sur le Médicament de Normandie (CERMN), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), GIP Cyceron (Cyceron), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), This work was supported by funding from the Fondation Vaincre Alzheimer (#FR-15072) and the Fondation Plan Alzheimer (AAP2015 Project TRIAD 016). The authors gratefully acknowledge the Conseil Régional de Normandie, as well as the European Community (FEDER) for their contribution to the CERMN’s analytical platform. European COST action CA15135 (Multi-Target Paradigm for Innovative Ligand Identification in the Drug Discovery Process, MuTaLig) supports this article., and Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 5-HT4 receptors, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Pharmaceutical Science, [CHIM.THER]Chemical Sciences/Medicinal Chemistry, Pharmacology, Ligands, Neuroprotection, Article, MTDL, Analytical Chemistry, lcsh:QD241-441, Pathogenesis, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, lcsh:Organic chemistry, Alzheimer Disease, In vivo, Drug Discovery, Humans, Medicine, Prodrugs, Physical and Theoretical Chemistry, Receptor, Active metabolite, 030304 developmental biology, 0303 health sciences, biology, business.industry, Organic Chemistry, Brain, acetylcholinesterase, Prodrug, Acetylcholinesterase, 3. Good health, chemistry, Chemistry (miscellaneous), Chaperone (protein), biology.protein, Molecular Medicine, Carbamates, Cholinesterase Inhibitors, Receptors, Serotonin, 5-HT4, prodrug, business, Alzheimer’s disease, 030217 neurology & neurosurgery
Abstract: Alzheimer&rsquo, s disease (AD) is a multifactorial neurodegenerative disease which is still poorly understood. The drugs currently used against AD, mainly acetylcholinesterase inhibitors (AChEI), are considered clinically insufficient and are responsible for deleterious side effects. AChE is, however, currently receiving renewed interest through the discovery of a chaperone role played in the pathogenesis of AD. But AChE could also serve as an activating protein for pleiotropic prodrugs. Indeed, inhibiting central AChE with brain-penetrating designed carbamates which are able to covalently bind to the enzyme and to concomitantly liberate active metabolites in the brain could constitute a clinically more efficient approach which, additionally, is less likely to cause peripheral side effects. We aim in this article to pave the road of this new avenue with an in vitro and in vivo study of pleiotropic prodrugs targeting both the 5-HT4 receptor and AChE, in order to display a neuroprotective activity associated with a sustained restoration of the cholinergic neurotransmission and without the usual peripheral side effects associated with classic AChEI. This plural activity could bring to AD patients effective, relatively safe, symptomatic and disease-modifying therapeutic benefits.
Published: 2019
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47. Occupations and the Risk of Head and Neck Cancer: A Pooled Analysis of the International Head and Neck Cancer Epidemiology (INHANCE) Consortium

Author: Kristina Kjærheim, Dana Hashim, Gwenn Menvielle, Hermann Brenner, Peter Thomson, Prerna Khetan, Diego Serraino, Pagona Lagiou, Carlo La Vecchia, Maria Paula Curado, Mia Hashibe, Lorenzo Richiardi, Yuan Chin Amy Lee, Danièle Luce, Wolfgang Ahrens, Joshua E. Muscat, Thomas L. Vaughan, Dana Mates, Isabelle Stücker, Heribert Ramroth, Paolo Boffetta, Victor Wünsch-Filho, David I. Conway, Ana M. B. Menezes, Icahn School of Medicine at Mount Sinai [New York] (MSSM), Institut de recherche en santé, environnement et travail (Irset), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Centre de recherche en épidémiologie et santé des populations (CESP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, International Prevention Research Institute (IPRI), Universidade Federal de Pelotas = Federal University of Pelotas (UFPel), Universidade de São Paulo (USP), Leibniz Institute for Prevention Research and Epidemiology - BIPS, Leibniz Association, National and Kapodistrian University of Athens (NKUA), University of Turin, Cancer Registry of Norway, University of Glasgow, The University of Hong Kong (HKU), Penn State College of Medicine, Penn State System-Pennsylvania Commonwealth System of Higher Education (PCSHE), National Institute of Public Health [Romania] (INSP), Heidelberg University Hospital [Heidelberg], Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Universität Heidelberg [Heidelberg], German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), University of Utah School of Medicine [Salt Lake City], Università degli Studi di Milano [Milano] (UNIMI), International Agency for Cancer Research (IACR), The INHANCE Consortium was supported by NIH grants NCI R03CA113157 and NIDCR R03DE016611. Studies participating in the pooled analysis were supported by: Latin America study: Fondo para la Investigacion Cientifica y Tecnologica (FONCYT) Argentina, IMIM (Barcelona), Fundaco de Amparo a` Pesquisa no Estado de Sao Paulo (FAPESP) [No 01/01768–2], and European Commission [IC18-CT97–0222]. Sao Paulo: Sao Paulo Research Foundation (FAPESP) (GENCAPO 04/12054–9, 10/51168–0). Western Europe multicenter (ARCAGE): European Community (5th Framework Programme) grant no QLK1-CT-2001-00182. New York multicenter: NY multicenter study: NIH [P01CA068384 K07CA104231]. Central Europe multicenter (INCO): Central Europe study: World Cancer Research Fund and the European Commission INCO-COPERNICUS Program [Contract No. IC15- CT98–0332]. Tampa study: NIH [P01CA068384, K07CA104231, R01DE013158] Germany-Heidelberg: Germany-Heidelberg study: grant No. 01GB9702/3 from the German Ministry of Education and Research. Seattle-Leo: Seattle-LEO study: NIH[R01CA030022]. MSKCC: MSKCC study: NIH [R01CA051845]. Germany-Saarland: Saarland study: Ministry of Science, Research and Arts Baden-Wurttemberg.. France multicenter (ICARE): French National Research Agency (ANR), French National Cancer Institute (INCA), French Agency for Food, Environmental and Occupational Health and Safety (ANSES), French Association for Research on Cancer (ARC), Fondation pour la Recherche Médicale (FRM), French Institute for Public Health Surveillance (InVS), Fondation de France, Ministry of Labour, Ministry of Health, LUCE, Danièle, Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Universidade de São Paulo = University of São Paulo (USP), Università degli studi di Torino = University of Turin (UNITO), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Penn State System, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Università degli Studi di Milano = University of Milan (UNIMI), Khetan P., Boffetta P., Luce D., Stucker I., Curado M.P., Menezes A., Wunsch-Filho V., Ahrens W., Lagiou P., Serraino D., Richiardi L., Kjaerheim K., Conway D., Thomson P., Muscat J., Mates D., Ramroth H., Menvielle G., Vaughan T.L., Brenner H., Lee Y.-C.A., La Vecchia C., Hashibe M., Hashim D., and Universität Heidelberg [Heidelberg] = Heidelberg University
Subjects: medicine.medical_specialty, Databases, Factual, Population, Logistic regression, Article, Pooled, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Epidemiology, medicine, Humans, education, Cancer, education.field_of_study, Occupation, business.industry, Head and neck cancer, Public Health, Environmental and Occupational Health, Odds ratio, medicine.disease, 030210 environmental & occupational health, Confidence interval, Europe, Occupational Diseases, Latin America, Logistic Models, Head and Neck Neoplasms, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Head, Larynx, Neck, Attributable risk, North America, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Demography
Abstract: Objective: To investigate the associations between head and neck cancer\ud (HNC) risk and occupations. Methods: We harmonized data on occupations\ud in a pooled analysis of 8839 HNC cases and 13,730 controls in International\ud Head and Neck Cancer Epidemiology (INHANCE) consortium. Logistic\ud regression was used to estimate odds ratios (ORs) for associations of\ud occupations and HNC risk. Population attributable fraction (PAF)\ud for occupations was calculated using the formula PEC (OR 1)/OR.1\ud Results: Trend of increasing HNC risk was found with increasing duration\ud of employment for many occupations, including cooks (OR ¼ 1.36; 95%\ud confidence interval [CI] 1.09 to 1.68), cleaners (OR ¼ 1.38; 95% CI 1.13 to\ud 1.69), painters (OR ¼ 1.82; 95% CI 1.42 to 2.35). The PAF for a priori\ud occupations was 14.5% (95% CI 7.1% to 21.9%) for HNC. Conclusions: We\ud found associations between certain occupations and HNC risks, including for\ud subsites, with a duration– response relationship.
Published: 2019
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48. Human predecidual stromal cells are mesenchymal stromal/stem cells and have a therapeutic effect in an immune-based mouse model of recurrent spontaneous abortion

Author: Carmen Ruiz-Ruiz, Claudia de la Mata, Pablo Fernandez-Rubio, Francisco Martin, María José Ruiz-Magaña, Tatiana Llorca, Raquel Muñoz-Fernández, Francisco Requena, Enrique G. Olivares, [Munoz-Fernandez,R, De La Mata,C, Fernandez-Rubio,P, Llorca,T, Ruiz-Magana,MJ, Ruiz-Ruiz,C, Olivares,EG] Instituto de Biopatología y Medicina Regenerativa, Centro de Investigación Biomédica, Universidad de Granada, Granada, Spain. [Requena,F] Departamento de Estadística e Investigación Operativa, Universidad de Granada, Granada, Spain. [Martín,F] Human DNA Variability Department, GENYO - Centre for Genomic and Oncological Research (Pfizer/University of Granada/Andalusian Regional Government), PTS Granada, Granada, Spain. [Ruiz-Ruiz,C, Olivares,EG] Departamento de Bioquímica y Biología Molecular III e Inmunología, Facultad de Medicina, Universidad de Granada, Granada, Spain. [Olivares,EG] Unidad de Gestión Clínica Laboratorios, Hospital Universitario San Cecilio, Granada, Spain., and This work was supported by the Plan Estatal de Investigación Científica y Técnica y de Innovación 2013–2016, ISCIII-Subdirección General de Evaluación y Fomento de la Investigación, the Ministerio de Economía y Competitividad, Spain (Grant PI16/01642) and European Regional Development Fund (ERDF/FEDER funding), the European Community, and the Cátedra de Investigación Antonio Chamorro–Alejandro Otero, Universidad de Granada (CACH2017-1).
Subjects: 0301 basic medicine, Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Differentiation [Medical Subject Headings], Mesenchymal stromal cells, Medicine (miscellaneous), Clone cells, Stem cell marker, Immune tolerance, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Endometrium, Mice, 0302 clinical medicine, Pregnancy, Organisms::Eukaryota::Animals [Medical Subject Headings], lcsh:QD415-436, Phenomena and Processes::Reproductive and Urinary Physiological Phenomena::Reproductive Physiological Phenomena::Reproductive Physiological Processes::Reproduction::Pregnancy [Medical Subject Headings], Cells, Cultured, Diseases::Female Urogenital Diseases and Pregnancy Complications::Pregnancy Complications::Abortion, Spontaneous [Medical Subject Headings], lcsh:R5-920, Cell Differentiation, Cell biology, 030220 oncology & carcinogenesis, Molecular Medicine, Female, Immunotherapy, Stem cell, lcsh:Medicine (General), Homeobox protein NANOG, Abortion, Habitual, Stromal cell, Células madre mesenquimatosas, Diseases::Female Urogenital Diseases and Pregnancy Complications::Pregnancy Complications::Abortion, Spontaneous::Abortion, Habitual [Medical Subject Headings], Analytical, Diagnostic and Therapeutic Techniques and Equipment::Surgical Procedures, Operative::Transplantation::Cell Transplantation::Stem Cell Transplantation::Mesenchymal Stem Cell Transplantation [Medical Subject Headings], Biology, Aborto habitual, Mesenchymal Stem Cell Transplantation, Biochemistry, Genetics and Molecular Biology (miscellaneous), lcsh:Biochemistry, 03 medical and health sciences, Células clonales, Decidua, Animals, Humans, Inmunoterapia, Tolerancia inmunológica, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::Mice [Medical Subject Headings], Research, Mesenchymal stem cell, Anatomy::Urogenital System::Genitalia::Genitalia, Female::Uterus::Endometrium [Medical Subject Headings], Decidualization, Anatomy::Embryonic Structures::Placenta::Decidua [Medical Subject Headings], Mesenchymal Stem Cells, Recurrent abortion, Cell Biology, Diseases::Animal Diseases::Disease Models, Animal [Medical Subject Headings], Abortion, Spontaneous, Disease Models, Animal, 030104 developmental biology, Check Tags::Female [Medical Subject Headings], Cell culture, Anatomy::Cells::Cells, Cultured [Medical Subject Headings], Predecidual stromal cells
Abstract: Human decidual stromal cells (DSCs) are involved in the maintenance and development of pregnancy, in which they play a key role in the induction of immunological maternal–fetal tolerance. Precursors of DSCs (preDSCs) are located around the vessels, and based on their antigen phenotype, previous studies suggested a relationship between preDSCs and mesenchymal stromal/stem cells (MSCs). This work aimed to further elucidate the MSC characteristics of preDSCs. Under the effect of P4 and cAMP, the preDSC lines and clones decidualized in vitro: the cells became rounder and secreted PRL, a marker of physiological decidualization. PreDSC lines and clones also exhibited MSC characteristics. They differentiated into adipocytes, osteoblasts, and chondrocytes, and preDSC lines expressed stem cell markers OCT- 4, NANOG, and ABCG2; exhibited a cloning efficiency of 4 to 15%; significantly reduced the embryo resorption rate (P < 0.001) in the mouse model of abortion; and survived for prolonged periods in immunocompetent mice. The fact that 3 preDSC clones underwent both decidualization and mesenchymal differentiation shows that the same type of cell exhibited both DSC and MSC characteristics. Together, our results confirm that preDSCs are decidual MSCs and suggest that these cells are involved in the mechanisms of maternal–fetal immune tolerance, This work was supported by the Plan Estatal de Investigación Científica y Técnica y de Innovación 2013–2016, ISCIII-Subdirección General de Evaluación y Fomento de la Investigación, the Ministerio de Economía y Competitividad, Spain (Grant PI16/01642) and European Regional Development Fund (ERDF/ FEDER funding), the European Community, and the Cátedra de Investigación Anto nio Chamorro–Alejandro Otero, Universidad de Granada (CACH2017-1).
Published: 2019

49. Theaflavins, polyphenols of black tea, inhibit entry of hepatitis C virus in cell culture

Author: Pritom Chowdhury, Marie-Emmanuelle Sahuc, Yves Rouillé, Céline Rivière, Natacha Bonneau, Alexandre Vandeputte, Priscille Brodin, Manoranjan Goswami, Tanoy Bandyopadhyay, Jean Dubuisson, Karin Séron, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Tocklai Tea Research Institute, Institut Charles Viollette (ICV) - EA 7394 (ICV), Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Institut National de la Recherche Agronomique (INRA)-Université d'Artois (UA)-Institut Supérieur d'Agriculture, PB and AV received support from the European Community (ERC-STG INTRACELLTB Grant n° 260901), the Agence Nationale de la Recherche (ANR-10-EQPX-04-01), the Feder (12001407 (D-AL) Equipex Imaginex BioMed) and the Région Nord Pas de Calais (convention n°12000080). PC received a post-doctoral overseas training fellowship from Department of Health Research, Ministry of Health and Family welfare, Government of India, The authors are thankful to Department of Health Research, Ministry of Health and Family welfare, Government of India, for providing post-doctoral overseas training fellowship to P. Chowdhury. The authors are also thankful to Director, TTRI and Secretary, TRA for their support to implement the research fellowship grant., European Project: 260901,EC:FP7:ERC,ERC-2010-StG_20091118,INTRACELLTB(2010), Centre d’Infection et d’Immunité de Lille (CIIL) - U1019 - UMR 8204 (CIIL), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Université d'Artois (UA)-Institut National de la Recherche Agronomique (INRA)-Université du Littoral Côte d'Opale (ULCO)-Institut Supérieur d'Agriculture-Université de Lille, Rouillé, Yves, and A Chemical Genomics Approach of Intracellular Mycobacterium tuberculosis Towards Defining Specific Host Pathogen Interactions - INTRACELLTB - - EC:FP7:ERC2010-12-01 - 2015-11-30 - 260901 - VALID
Subjects: RNA viruses, Physiology, Immunofluorescence, Hepacivirus, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Antiviral therapy, Biochemistry, Antioxidants, Camellia sinensis, Catechin, Virions, Immune Physiology, Viral replication, Public and Occupational Health, Pathology and laboratory medicine, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Immune System Proteins, Antimicrobials, Hepatitis C virus, Drugs, virus diseases, Medical microbiology, Antivirals, Vaccination and Immunization, Liver, Viruses, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Medicine, Pathogens, Research Article, Science, Immunology, Viral Structure, Research and Analysis Methods, Antiviral Agents, Microbiology, Antibodies, Beverages, Cell Line, Tumor, Microbial Control, Virology, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Biflavonoids, Humans, Immunoassays, Nutrition, Medicine and health sciences, Pharmacology, Dose-Response Relationship, Drug, Biology and life sciences, Flaviviruses, Tea, Organisms, Viral pathogens, Polyphenols, Proteins, Hepatitis viruses, digestive system diseases, Microbial pathogens, Diet, Immunologic Techniques, Preventive Medicine
Abstract: International audience; The treatment of hepatitis C virus (HCV) infection by combination of direct acting antivirals (DAA), with different mode of action, has made substantial progress in the past few years. However, appearance of resistance and high cost of the therapy is still an obstacle in the achievement of the therapy, more specifically in developing countries. In this context, search for affordable antivirals with new mechanisms of action is still needed. Tea, after water, is the most popular drink worldwide. Polyphenols extracted from green tea have already shown anti-HCV activity as entry inhibitors. Here, three different theaflavins, theaflavin (TF1), theaflavin-3'-monogallate (TF2), and theaflavin-3-3'-digallate (TF3), which are major polyphenols from black tea, were tested against HCV in cell culture. The results showed that all theaflavins inhibit HCV infection in a dose-dependent manner in an early step of infection. Results obtained with HCV pseudotyped virions confirmed their activity on HCV entry and demonstrated their pan-genotypic action. No effect on HCV replication was observed by using HCV replicon. Investigation on the mechanism of action of black tea theaflavins showed that they act directly on the virus particle and are able to inhibit cell-to-cell spread. Combination study with inhibitors most widely used in anti-HCV treatment regimen demonstrated that TF3 exerts additive effect. In conclusion, theaflavins, that are present in high quantity in black tea, are new inhibitors of HCV entry and hold promise for developing in therapeutic arsenal for HCV infection.
Published: 2018
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50. Relation between hysterectomy, oophorectomy and the risk of incident differentiated thyroid cancer: The E3N cohort

Author: Sylvie Mesrine, Françoise Clavel-Chapelon, Marina Kvaskoff, Laureen Dartois, Laurence Leenhardt, Agathe Guenego, Marie-Christine Boutron-Ruault, Fabrice Bonnet, CHU Pontchaillou [Rennes], Institut Gustave Roussy (IGR), Centre de recherche en épidémiologie et santé des populations (CESP), 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 de médecine nucléaire [CHU Pitié-Salpétrière], 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), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES), Mutuelle Générale de l’Education Nationale (MGEN), European Community, French League against Cancer (LNCC), Gustave Roussy, French National Institutes for Health and Medical Research (Inserm), French National Cancer Institute (InCA) (#2009‐139), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Université de Rennes (UR), Service de Médecine nucléaire [CHU Pitié-Salpétrière], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Adult, medicine.medical_specialty, Uterine fibroids, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Ovariectomy, 030209 endocrinology & metabolism, fibroids, [SDV.CAN]Life Sciences [q-bio]/Cancer, Hysterectomy, 03 medical and health sciences, Uterine polyps, 0302 clinical medicine, Endocrinology, oophorectomy, Risk Factors, Internal medicine, medicine, thyroid cancer, Humans, Thyroid Neoplasms, Prospective cohort study, Thyroid cancer, Leiomyoma, business.industry, Obstetrics, Thyroid disease, Incidence, Thyroid, Oophorectomy, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Middle Aged, medicine.disease, 3. Good health, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Female, France, business, Genital Diseases, Female, Follow-Up Studies
Abstract: International audience; BACKGROUND:Thyroid cancers are threefold more frequent in women than in men. A role of reproductive or hormonal factors has been suggested but with contradictory results. We investigated potential associations between history of hysterectomy, with or without oophorectomy, and history of benign gynaecological disease (uterine fibroids, endometriosis) and the incidence of differentiated thyroid cancer, in a large French prospective cohort.METHODS:A total of 89 340 women from the E3N cohort were followed up between 1990 and 2012. Gynaecological diseases treated by surgery were self-reported. Thyroid cancers were validated by histological reports. Time-dependent covariates included smoking status, BMI and history of benign thyroid disease. Cox proportional hazard models with age as timescale were used to estimate Hazard Ratios (HR) and 95% confidence intervals (CI).RESULTS:A total of 412 cases of thyroid cancer were diagnosed during follow-up. A history of hysterectomy was associated with an increased risk of differentiated thyroid cancer (adjusted HR=2.05; 95%CI: 1.65-2.55). The association was not altered after further adjustment for reproductive factors. Endometriosis, uterine polyps, ovarian cysts and oophorectomy without hysterectomy were not associated with the risk of thyroid cancer. A history of fibroids was also significantly related to the risk of thyroid cancer over the follow-up period (adjusted HR=1.91; 95%CI: 1.50-2.44) and the increased risk persisted after adjustment for history of hysterectomy.CONCLUSIONS:Women who had either a history of fibroids or hysterectomy had an increased risk of differentiated thyroid cancer. These findings suggest shared biological mechanisms between fibroids and thyroid cancer, which deserve to be further dissected.
Published: 2018
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