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1. Effect of an enteral amino acid blend on muscle and gut functionality in critically ill patients: a proof-of-concept randomized controlled trial

Author: Heming, Nicholas, Carlier, Robert Yves, Prigent, Hélène, Mekki, Ahmed, Jousset, Camille, Lofaso, Frédéric, Ambrosi, Xavier, Bounab, Rania, Maxime, Virginie, Mansart, Arnaud, Crenn, P., Moine, Pierre, Foltzer, Fabien, Cuenoud, Bernard, Konz, Tobias, Corthesy, John, Beaumont, Maurice, Hartweg, Mickaël, Roessle, Claudia, Preiser, Jean Charles E., Breuillé, Denis, Annane, Djillali, HAL UVSQ, Équipe, Infection et inflammation (2I), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Raymond Poincaré [Garches], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), AP-HP. Université Paris Saclay, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre hospitalier universitaire de Nantes (CHU Nantes), Nestlé Research Center | Centre de recherche Nestlé [Lausanne], Nestlé S.A., Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Université libre de Bruxelles (ULB), Nestlé Health Science, and This study was funded by Nestlé Health Science. The experimental product, placebo and feed were all provided by Nestlé Health Science. Nestlé employees were involved in designing the study and in writing the manuscript.
Subjects: [SDV]Life Sciences [q-bio], Critical Illness, Muscles, Alanine Transaminase, Critical Care and Intensive Care Medicine, Alkaline Phosphatase, [SDV] Life Sciences [q-bio], Protein balance, Sepsis, Creatinine, Humans, Citrulline, Intensive care unit, Nutrition
Abstract: Background A defining feature of prolonged critical illness is muscle wasting, leading to impaired recovery. Supplementation with a tailored blend of amino acids may bolster the innate gut defence, promote intestinal mucosa repair and limit muscle loss. Methods This was a monocentric, randomized, double-blind, placebo-controlled study that included patients with sepsis or acute respiratory distress syndrome. Patients received a specific combination of five amino acids or placebo mixed with enteral feeding for 21 days. Markers of renal function, gut barrier structure and functionality were collected at baseline and 1, 2, 3 and 8 weeks after randomization. Muscle structure and function were assessed through MRI measurements of the anterior quadriceps volume and by twitch airway pressure. Data were compared between groups relative to the baseline. Results Thirty-five critically ill patients were randomized. The amino acid blend did not impair urine output, blood creatinine levels or creatinine clearance. Plasma citrulline levels increased significantly along the treatment period in the amino acid group (difference in means [95% CI] 5.86 [1.72; 10.00] nmol/mL P = 0.007). Alanine aminotransferase and alkaline phosphatase concentrations were lower in the amino acid group than in the placebo group at one week (ratio of means 0.5 [0.29; 0.86] (P = 0.015) and 0.73 [0.57; 0.94] (P = 0.015), respectively). Twitch airway pressure and volume of the anterior quadriceps were greater in the amino acid group than in the placebo group 3 weeks after randomization (difference in means 10.6 [0.99; 20.20] cmH20 (P = 0.035) and 3.12 [0.5; 5.73] cm3/kg (P = 0.022), respectively). Conclusions Amino acid supplementation increased plasma citrulline levels, reduced alanine aminotransferase and alkaline phosphatase levels, and improved twitch airway pressure and anterior quadriceps volume. Trial registration ClinicalTrials.gov, NCT02968836. Registered November 21, 2016.
Published: 2022

2. OBEDIS Core Variables Project: European Expert Guidelines on a Minimal Core Set of Variables to Include in Randomized, Controlled Clinical Trials of Obesity Interventions

Author: António L. Palmeira, Thorkild I. A. Sørensen, Martin Neovius, Martine Laville, Mikael Rydén, Andrea Natali, Maud Alligier, Romain Barrès, Kristina Campbell, David Jacobi, I. Sadaf Farooqi, Jean-Michel Oppert, Helen M. Roche, André Scheen, Karine Clément, Ellen E. Blaak, Yves Boirie, Gijs H. Goossens, Jason C.G. Halford, Luc Tappy, Nathalie Farpour-Lambert, Hannele Yki-Järvinen, Uberto Pagotto, Chantal Simon, Jörg Hager, Jildau Bouwman, Paul Brunault, Gema Frühbeck, Dominique Langin, Olivier Ziegler, Chantal Julia, Hans Hauner, Centre de Recherche en Nutrition Humaine Rhône-Alpes (CRNH-RA), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), University of Copenhagen = Københavns Universitet (KU), Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], CHU Clermont-Ferrand, Netherlands Organization for Applied Scientific Research (TNO), TNO Science and Industry, Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Tours (UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), KC Microbiome Communications Group, Nutrition et obésités: approches systémiques (nutriomics) (UMR-S 1269 INSERM - Sorbonne Université), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), NIHR Biomedical Research Centre [London], Guy's and St Thomas' NHS Foundation Trust-King‘s College London, University of Cambridge [UK] (CAM), Université de Genève (UNIGE), Geneva University Hospitals and Geneva University, Clínica Universidad de Navarra [Pamplona], Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], University of Liverpool, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Klinikums rechts der Isar, Centre National de la Recherche Scientifique (CNRS), Université de Nantes (UN), unité de recherche de l'institut du thorax UMR1087 UMR6291 (ITX), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Sorbonne Paris Nord-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)-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)-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), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Pisa - Università di Pisa, Karolinska Institutet [Stockholm], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Alma Mater Studiorum University of Bologna (UNIBO), Université de Lisbonne, University College Dublin [Dublin] (UCD), Centre Hospitalier Universitaire de Liège (CHU-Liège), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Université de Lausanne (UNIL), Minerva Foundation Institute for Medical Research, University of Helsinki, Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Joint Programming Initiative Heathy Diet for Healthy Life, Alligier M., Barres R., Blaak E.E., Boirie Y., Bouwman J., Brunault P., Campbell K., Clement K., Farooqi I.S., Farpour-Lambert N.J., Fruhbeck G., Goossens G.H., Hager J., Halford J.C.G., Hauner H., Jacobi D., Julia C., Langin D., Natali A., Neovius M., Oppert J.M., Pagotto U., Palmeira A.L., Roche H., Ryden M., Scheen A.J., Simon C., Sorensen T.I.A., Tappy L., Yki-Jarvinen H., Ziegler O., Laville M., FCRIN/FORCE Network, Centre de Recherche en Nutrition Humaine Rhône-Alpes, Novo Nordisk, Department of Human Biology, Maastricht University Medical Center (MUMC), Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Nutrition clinique, Centre Hospitalier Universitaire Gabriel Montpied, TNO,Netherlands Organisation for Applied Scientific Research, UMR U 1253, Université de Tours, Nutrition et obésité : approches systémiques, Sorbonne Université, Wellcome-MRC Institute of Metabolic Science and NIHR Biomedical Research Centre, University of Cambridge, Service of Therapeutic Education for Chronic Diseases, Department of Community Health, Primary Care and Emergency, Geneva University Hospitals, Department of Endocrinology and Nutrition, Navarra Public Health Institute, Centro de Investigación Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición - Biomedical Research Center in Red-Physiopathology of Obesity and Nutrition (CIBEROBN), University of Navarra, University of Cape Town, Metabolic Phenotyping, Nestlé Institute of Health Sciences, Psychological Sciences, University of Liverpool (University of Liverpool), Institut für Ernährungsmedizin des Klinikums Rechts der Isar, Technical University of Munich (TUM), Institut du Thorax, Centre Hospitalier Universitaire de Nantes, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC), Université Toulouse III - Paul Sabatier, Centre Hospitalier Universitaire de Toulouse, Department of Clinical and Experimental Medicine, Università degli studi di Napoli Federico II, Department of Medicine (Solna), Nutrition, Institut de Cardiométabolisme et Nutrition (ICAN), CHU Pitié-Salpêtrière [APHP], Department of Medical and Surgical Sciences, Universita degli Studi di Padova, CIPER, PANO-SR, Faculty of Human Kinetics, University of Lisbon, UCD Institute of Food and Health, University College Dublin (UCD), Department of Medicine, The University of Sydney, Diabètes, Nutrition et maladies métaboliques, Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Physiologie, Université de Picardie Jules Verne (UPJV), Helsinki University Central Hospital, Endocrinologie, Diabetes et Nutrition, Hôpital Brabois, Maastricht University [Maastricht]-Maastricht University [Maastricht], Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), 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), Sorbonne Université-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), 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, ProdInra, Archive Ouverte, Université de Lyon-Université de Lyon-CHU Grenoble-Hospices Civils de Lyon (HCL)-CHU Saint-Etienne-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Grenoble Alpes (UGA), University of Copenhagen = Københavns Universitet (UCPH), University of Copenhagen = Københavns Universitet (UCPH)-University of Copenhagen = Københavns Universitet (UCPH), Nutrition et obésités: approches systémiques (UMR-S 1269) (Nutriomics), Université de Genève = University of Geneva (UNIGE), Unité de recherche de l'institut du thorax (ITX-lab), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), 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)-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), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut de Cardiométabolisme et Nutrition = Institute of Cardiometabolism and Nutrition [CHU Pitié Salpêtrière] (IHU ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-CHU Pitié-Salpêtrière [AP-HP], Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Lausanne = University of Lausanne (UNIL), Helsingin yliopisto = Helsingfors universitet = University of Helsinki, HUS Internal Medicine and Rehabilitation, Humane Biologie, and RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health
Subjects: 0301 basic medicine, Research design, Gerontology, Health (social science), Psychological intervention, Choice Behavior, 0302 clinical medicine, QUALITY-OF-LIFE, OBSTRUCTIVE SLEEP-APNEA, Medicine, Medical History Taking, lcsh:RC620-627, Interventions, METABOLIC SYNDROME, Randomized Controlled Trials as Topic, ddc:616, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Precision medicine, Prognosis, C-REACTIVE PROTEIN, 3. Good health, Europe, lcsh:Nutritional diseases. Deficiency diseases, CARDIOVASCULAR-DISEASE, Research Design, Variable, lcsh:Nutrition. Foods and food supply, Human, Prognosi, education, WEIGHT-LOSS, lcsh:TX341-641, Intervention, 030209 endocrinology & metabolism, GASTRIC BYPASS-SURGERY, Guidelines, Patient care, 03 medical and health sciences, Variables, Physiology (medical), Humans, CORONARY-HEART-DISEASE, Obesity, Expert Testimony, Core set, 030109 nutrition & dietetics, business.industry, Stratification, medicine.disease, Diet, BODY-MASS INDEX, Clinical trial, PHYSICAL-ACTIVITY, Biological Variation, Population, 3121 General medicine, internal medicine and other clinical medicine, Metabolic syndrome, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Heterogeneity of interindividual and intraindividual responses to interventions is often observed in randomized, controlled trials for obesity. To address the global epidemic of obesity and move toward more personalized treatment regimens, the global research community must come together to identify factors that may drive these heterogeneous responses to interventions. This project, called OBEDIS (OBEsity Diverse Interventions Sharing - focusing on dietary and other interventions), provides a set of European guidelines for a minimal set of variables to include in future clinical trials on obesity, regardless of the specific endpoints. Broad adoption of these guidelines will enable researchers to harmonize and merge data from multiple intervention studies, allowing stratification of patients according to precise phenotyping criteria which are measured using standardized methods. In this way, studies across Europe may be pooled for better prediction of individuals' responses to an intervention for obesity - ultimately leading to better patient care and improved obesity outcomes. © 2020 The Author(s) Published by S. Karger AG, Basel.
Published: 2020

3. The Dietary Inflammatory Index Is Associated with Subclinical Mastitis in Lactating European Women

Author: Myriam C. Afeiche, Alison Iroz, Frank Thielecke, Antonio C. De Castro, Gregory Lefebvre, Colleen F. Draper, Cecilia Martínez-Costa, Kirsti Haaland, Giovanna Marchini, Massimo Agosti, Magnus Domellöf, Thameur Rakza, Maria José Costeira, Mireille Vanpee, Claude Billeaud, Jean-Charles Picaud, Daryl Lim Kah Hian, Guimei Liu, Nitin Shivappa, James R. Hébert, Tinu M. Samuel, Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Swiss Distance University of Applied Sciences [Regensdorf-Zurich, Switzerland] (SDUAS), SAS Institute Pte Ltd. [Singapore], Crown Bioscience [San Diego, CA, USA] (CB), EPFL Innovation Park [Lausanne, Switzerland], Universitat de València (UV), Oslo University Hospital [Oslo], Karolinska University Hospital [Stockholm], Ospedale del Ponte [Varese, Italy], Universitá degli Studi dell’Insubria = University of Insubria [Varese] (Uninsubria), Umeå University, Centre d'Investigation Clinique - Innovation Technologique de Lille - CIC 1403 - CIC 9301 (CIC Lille), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Instituto de Investigação em Ciências da Vida e Saúde [Braga, Portugal] (Escola de Ciências da Saúde), Universidade do Minho = University of Minho [Braga], CHU de Bordeaux Pellegrin [Bordeaux], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Institute for Infocomm Research - I²R [Singapore], University of South Carolina [Columbia], and CarMeN, laboratoire
Subjects: Nutrition and Dietetics, Milk, Human, [SDV.BA] Life Sciences [q-bio]/Animal biology, [SDV.BA]Life Sciences [q-bio]/Animal biology, lactating women, dietary inflammatory index, subclinical mastitis, multicenter longitudinal cohort, Sodium, Mastitis, Mastitis/complications, Diet, Näringslära, Milk, Lactation, Humans, Human/chemistry, Female, Sodium/analysis, Food Science
Abstract: International audience; Subclinical mastitis (SCM) is an inflammatory state of the lactating mammary gland, which is asymptomatic and may have negative consequences for child growth. The objectives of this study were to: (1) test the association between the dietary inflammatory index (DII(®)) and SCM and (2) assess the differences in nutrient intakes between women without SCM and those with SCM. One hundred and seventy-seven women with available data on human milk (HM) sodium potassium ratio (Na:K) and dietary intake data were included for analysis. Multivariable logistic regression was used to examine the association between nutrient intake and the DII score in relation to SCM. Women without SCM had a lower median DII score (0.60) than women with moderate (1.12) or severe (1.74) SCM (p < 0.01). A one-unit increase in DII was associated with about 41% increased odds of having SCM, adjusting for country and mode of delivery, p = 0.001. Women with SCM had lower mean intakes of several anti-inflammatory nutrients. We show for the first time exploratory evidence that SCM may be associated with a pro-inflammatory diet and women with SCM have lower intakes of several antioxidant and anti-inflammatory nutrients.
Published: 2022

4. Mode of Neonatal Delivery Influences the Nutrient Composition of Human Milk: Results From a Multicenter European Cohort of Lactating Women

Author: Tinu M. Samuel, Frank Thielecke, Luca Lavalle, Cheng Chen, Paul Fogel, Francesca Giuffrida, Stephane Dubascoux, Cecilia Martínez-Costa, Kirsti Haaland, Giovanna Marchini, Massimo Agosti, Thameur Rakza, Maria Jose Costeira, Jean-Charles Picaud, Claude Billeaud, Sagar K. Thakkar, Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Swiss Distance University of Applied Sciences [Regensdorf-Zurich, Switzerland] (SDUAS), Advestis [Paris] (AP), Universitat de València (UV), Oslo University Hospital [Oslo], Karolinska University Hospital [Stockholm], Ospedale del Ponte [Varese, Italy], Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Instituto de Investigação em Ciências da Vida e Saúde [Braga, Portugal] (Escola de Ciências da Saúde), Universidade do Minho = University of Minho [Braga], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), CHU de Bordeaux Pellegrin [Bordeaux], and CarMeN, laboratoire
Subjects: [SDV] Life Sciences [q-bio], vaginal birth, C-section = caesarean section, Nutrition and Dietetics, mode of delivery, inflammation, Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], longitudinal cohort, human milk, Food Science
Abstract: BackgroundThe effect of the mode of neonatal delivery (cesarean or vaginal) on the nutrient composition of human milk (HM) has rarely been studied. Given the increasing prevalence of cesarean section (C-section) globally, understanding the impact of C-section vs. vaginal delivery on the nutrient composition of HM is fundamental when HM is the preferred source of infant food during the first 4 postnatal months.ObjectiveThis study aimed to evaluate the association between mode of delivery and nutrient composition of HM in the first 4 months of life.DesignMilk samples were obtained from 317 healthy lactating mothers as part of an exploratory analyses within a multicenter European longitudinal cohort (ATLAS cohort) to study the HM composition, and its potential association with the mode of delivery. We employed traditional mixed models to study individual nutrient associations adjusted for mother’s country, infant birth weight, parity, and gestational age, and complemented it, for the first time, with a multidimensional data analyses approach (non-negative tensor factorization, NTF) to examine holistically how patterns of multiple nutrients and changes over time are associated with the delivery mode.ResultsOver the first 4 months, nutrient profiles in the milk of mothers who delivered vaginally (n = 237) showed significantly higher levels of palmitoleic acid (16:1n-7), stearic acid (18:0), oleic acid (18:1n-9), arachidic acid (20:0), alpha-linolenic acid (18:3n-3), eicosapentaenoic acid (20:5n-3), docosahexenoic acid (22:6n-3), erucic acid (22:1n-9), monounsaturated fatty acids (MUFA)%, calcium, and phosphorus, whereas the ratios of arachidonic acid/docosahexaenoic acid (ARA/DHA) and n-6/n-3, as well as polyunsaturated fatty acids (PUFA)% were higher in milk from women who had C-sections, in the unadjusted analyses (p < 0.05 for all), but did not retain significance when adjusted for confounders in the mixed models. Using a complementary multidimension data analyses approach (NTF), we show few similar patterns wherein a group of mothers with a high density of C-sections showed increased values for PUFA%, n-6/n-3, and ARA/DHA ratios, but decreased values of MUFA%, 20:1n-9, iodine, and fucosyl-sialyl-lacto-N-tetraose 2 during the first 4 months of lactation.ConclusionOur data provide preliminary insights on differences in concentrations of several HM nutrients (predominantly fatty acids) among women who delivered via C-section. Although these effects tend to disappear after adjustment for confounders, given the similar patterns observed using two different data analytical approaches, these preliminary findings warrant further confirmation and additional insight on the biological and clinical effects related to such differences early in life.
Published: 2022

5. Hyperactivation of monocytes and macrophages in MCI patients contributes to the progression of Alzheimer's disease

Author: Jean-Pierre Bellenger, Benoit Laurent, Nabil Bosco, Tamas Fulop, Katsuiku Hirokawa, Eric Frost, Pascale B. Beauregard, Abdelouahed Khalil, David Dumoulin, Weili Xu, Mathieu Desroches, Simon Lévesque, Stephen C. Cunnane, Annelise E. Barron, Anis Larbi, Charles Ramassamy, Michael Catanzaro, Serafim Rodrigues, Usma Munawara, Crystal Tze Ying Tan, Jacek M. Witkowski, Centre de recherche sur le vieillissement - CSSS-UIGS (Université de Sherbrooke), Università degli Studi di Pavia = University of Pavia (UNIPV), Agency for science, technology and research [Singapore] (A*STAR), Tokyo Medical and Dental University [Japan] (TMDU), Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Université de Sherbrooke / Sherbrooke University (UdS), INRS-Centre Armand-Frappier Sante Biotechnologie, Stanford School of Medicine [Stanford], Stanford Medicine, Stanford University-Stanford University, Ikerbasque - Basque Foundation for Science, Basque Center for Applied Mathematics (BCAM), Basque Center for Applied Mathematics, Mathématiques pour les Neurosciences (MATHNEURO), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria), Université Côte d'Azur (UCA), and Medical University of Gdańsk
Subjects: 0301 basic medicine, Aging, Immunology, [MATH.MATH-DS]Mathematics [math]/Dynamical Systems [math.DS], free radicals, Systemic inflammation, Peripheral blood mononuclear cell, 03 medical and health sciences, 0302 clinical medicine, Immune system, medicine, Dementia, Macrophage, Neuroinflammation, MCI neuroinflammation, Microglia, business.industry, Monocyte, Research, [SCCO.NEUR]Cognitive science/Neuroscience, RC952-954.6, phagocytosis, RC581-607, medicine.disease, cytokines, 3. Good health, macrophages, 030104 developmental biology, medicine.anatomical_structure, Geriatrics, Immunologic diseases. Allergy, medicine.symptom, business, monocytes, signaling, Alzheimer’s disease, 030217 neurology & neurosurgery
Abstract: Background Alzheimer’s disease (AD) is the most common neurodegenerative disease ultimately manifesting as clinical dementia. Despite considerable effort and ample experimental data, the role of neuroinflammation related to systemic inflammation is still unsettled. While the implication of microglia is well recognized, the exact contribution of peripheral monocytes/macrophages is still largely unknown, especially concerning their role in the various stages of AD. Objectives AD develops over decades and its clinical manifestation is preceded by subjective memory complaints (SMC) and mild cognitive impairment (MCI); thus, the question arises how the peripheral innate immune response changes with the progression of the disease. Therefore, to further investigate the roles of monocytes/macrophages in the progression of AD we assessed their phenotypes and functions in patients at SMC, MCI and AD stages and compared them with cognitively healthy controls. We also conceptualised an idealised mathematical model to explain the functionality of monocytes/macrophages along the progression of the disease. Results We show that there are distinct phenotypic and functional changes in monocyte and macrophage populations as the disease progresses. Higher free radical production upon stimulation could already be observed for the monocytes of SMC patients. The most striking results show that activation of peripheral monocytes (hyperactivation) is the strongest in the MCI group, at the prodromal stage of the disease. Monocytes exhibit significantly increased chemotaxis, free radical production, and cytokine production in response to TLR2 and TLR4 stimulation. Conclusion Our data suggest that the peripheral innate immune system is activated during the progression from SMC through MCI to AD, with the highest levels of activation being in MCI subjects and the lowest in AD patients. Some of these parameters may be used as biomarkers, but more holistic immune studies are needed to find the best period of the disease for clinical intervention.
Published: 2021

6. High hydrostatic pressure processing of human milk preserves milk oligosaccharides and avoids formation of Maillard reaction products

Author: Edwina Micours, Marie de Lamballerie, Frédéric Gottrand, Delphine Ley, Jean Lesage, Sarahi Jaramillo-Ortiz, Mike Howsam, Lucie Marousez, Léa Tran, Norbert Sprenger, Frédéric J. Tessier, Institute for Translational Research in Inflammation - U 1286 (INFINITE (Ex-Liric)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Nestlé Research Center | Centre de recherche Nestlé [Lausanne], Nestlé S.A., Matrices Aliments Procédés Propriétés Structure - Sensoriel (GEPEA-MAPS2), Laboratoire de génie des procédés - environnement - agroalimentaire (GEPEA), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT)-Nantes université - UFR des Sciences et des Techniques (Nantes univ - UFR ST), Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Sciences et technologie, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - Institut Universitaire de Technologie Saint-Nazaire (Nantes Univ - IUT Saint-Nazaire), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Centre National de la Recherche Scientifique (CNRS)-IMT Atlantique (IMT Atlantique), Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 (RID-AGE), 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), Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), ANR-18-CE21-0005,HHP-humanmilk,Le traitement du lait maternel par haute pression hydrostatique augmente ses qualités biologiques et intestinotrophiques : études expérimentales ex-vivo et chez le nouveau-né prématuré.(2018), Université de Lille, Inserm, CHU Lille, Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286, Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Laboratoire de génie des procédés - environnement - agroalimentaire [GEPEA], Facteurs de Risque et Déterminants Moléculaires des Maladies liées au Vieillissement - U 1167 [RID-AGE], Institute for Translational Research in Inflammation - U 1286 [INFINITE (Ex-Liric)], Lille Inflammation Research International Center (LIRIC) - U995, and Facteurs de risque et déterminants moléculaires des maladies liées au vieillissement (RID-AGE) - U1167
Subjects: Glycation End Products, Advanced, Food Handling, Hydrostatic pressure, Oligosaccharides, Critical Care and Intensive Care Medicine, Hop (networking), symbols.namesake, High hydrostatic pressure, Tandem Mass Spectrometry, [SDV.IDA]Life Sciences [q-bio]/Food engineering, Hydrostatic Pressure, Medicine, Humans, Carboxyethyllysine, Food science, Holder pasteurization, Nutrition and Dietetics, Maillard reaction products, Milk, Human, business.industry, Human milk, Human milk oligosaccharides, food and beverages, Lactuloselysine, Raw milk, Mass spectrometric, Maillard reaction, symbols, business, [CHIM.OTHE]Chemical Sciences/Other, Chromatography, Liquid
Abstract: International audience; Background & aims: High hydrostatic pressure (HHP) processing is a non-thermal method proposed as an alternative to Holder pasteurization (HoP) for the treatment of human milk. HHP preserves numerous milk bioactive components that are degraded by HoP, but no data are available for milk oligosaccharides (HMOs) or the formation of Maillard reaction products, which may be deleterious for preterm newborns.Methods: We evaluated the impact of HHP processing of human milk on 22 HMOs measured by liquid chromatography with fluorescence detection and on furosine, lactuloselysine, carboxymethyllysine (CML) and carboxyethyllysine (CEL) measured by liquid chromatography with tandem mass spectrometric detection (LC-MS/MS), four established indicators of the Maillard reaction. Human raw milk was sterilized by HoP (62.5 °C for 30 min) or processed by HHP (350 MPa at 38 °C).Results: Neither HHP nor HoP processing affected the concentration of HMOs, but HoP significantly increased furosine, lactuloselysine, CML and CEL levels in milk.Conclusions: Our findings demonstrate that HPP treatment preserves HMOs and avoids formation of Maillard reaction products. Our study confirms and extends previous findings that HHP treatment of human milk provides safe milk, with fewer detrimental effects on the biochemically active milk components than HoP.
Published: 2021

7. Chemical genetic screen identifies Gapex-5/GAPVD1 and STBD1 as novel AMPK substrates

Author: Olga Göransson, Susanne Seitz, Philipp Gut, Maria Deak, Anja Zeigerer, Agnete B. Madsen, Marc Foretz, Benoit Viollet, David Sumpton, Thomas E. Jensen, Kei Sakamoto, Caterina Collodet, Serge Ducommun, Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Max-Planck-Gesellschaft, Department of Experimental Medical Sciences [Lund], Lund University [Lund], German Research Center for Environmental Health - Helmholtz Center München (GmbH), Department of Nutrition, Exercise and Sports [Copenhagen], Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Cancer Research UK Beatson Institute [Glasgow]
Subjects: 0301 basic medicine, Regulator, Muscle Proteins, AMP-Activated Protein Kinases, Mass Spectrometry, Substrate Specificity, 03 medical and health sciences, 0302 clinical medicine, Faculty of Science, Animals, Guanine Nucleotide Exchange Factors, Homeostasis, Phosphorylation, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Protein kinase A, Mice, Knockout, Effector, Activator (genetics), Chemistry, Starch-binding domain 1, Membrane Proteins, AMPK, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Shokat, Cell Biology, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Lipid Metabolism, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Cell biology, 030104 developmental biology, Liver, GTPase activating protein and VPS9 domains 1, 030220 oncology & carcinogenesis, Hepatocytes, Genetic screen
Abstract: International audience; AMP-activated protein kinase (AMPK) is a key regulator of cellular energy homeostasis, acting as a sensor of energy and nutrient status. As such, AMPK is considered a promising drug target for treatment of medical conditions particularly associated with metabolic dysfunctions. To better understand the downstream effectors and physiological consequences of AMPK activation, we have employed a chemical genetic screen in mouse primary hepatocytes in an attempt to identify novel AMPK targets. Treatment of hepatocytes with a potent and specific AMPK activator 991 resulted in identification of 65 proteins phosphorylated upon AMPK activation, which are involved in a variety of cellular processes such as lipid/glycogen metabolism, vesicle trafficking, and cytoskeleton organisation. Further characterisation and validation using mass spectrometry followed by immunoblotting analysis with phosphorylation site-specific antibodies identified AMPK-dependent phosphorylation of Gapex-5 (also known as GTPase-activating protein and VPS9 domain-containing protein 1 (GAPVD1)) on Ser902 in hepatocytes and starch-binding domain 1 (STBD1) on Ser175 in multiple cells/tissues. As new promising roles of AMPK as a key metabolic regulator continue to emerge, the substrates we identified could provide new mechanistic and therapeutic insights into AMPK-activating drugs in the liver.
Published: 2019

8. Network Analyses Reveal Negative Link Between Changes in Adipose Tissue GDF15 and BMI During Dietary-induced Weight Loss

Author: Aline Charpagne, Ondine Walter, Nathalie Viguerie, Julien Marquis, Jörg Hager, Nathalie Boulet, Sylviane Metairon, Julie Vion, Claire Laurens, Arne Astrup, Dominique Langin, Armand Valsesia, Nathalie Vialaneix, Alyssa Imbert, Wim H. M. Saris, Gregory Lefebvre, Cedric Moro, RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, Humane Biologie, Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), 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), Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRAE), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université de Lausanne, Genomic Technologies Facility, Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Franco-czech Laboratory for clinical research on obesity, Charles University [Prague] (CU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Toulouse University Hospitals, Laboratory of Clinical Biochemistry, Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], IT University of Copenhagen (ITU), Institut National de la Sante et de la Recherche Medicale (Inserm), Paul Sabatier University, Innovative Medicines Initiative Joint Undertaking115372, European CommissionFP6-513946 DiOGenes, and Vialaneix, Nathalie
Subjects: FOS: Computer and information sciences, Male, Weight loss, low calorie diet, PROMOTES, Macrophage, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Adipose tissue, Biochemistry, Body Mass Index, Transcriptome, chemistry.chemical_compound, network analyses, Endocrinology, [STAT.AP] Statistics [stat]/Applications [stat.AP], Adipocyte, Gene expression, Faculty of Science, OSTEOPONTIN, Gene Regulatory Networks, MACROPHAGES, [STAT.AP]Statistics [stat]/Applications [stat.AP], Prognosis, DIFFERENTIATION, Adipose Tissue, Network analyses, Female, medicine.symptom, EXPRESSION, Adult, medicine.medical_specialty, Growth Differentiation Factor 15, Diet, Reducing, Calorie restriction, Context (language use), macrophage, Biology, Statistics - Applications, Internal medicine, Weight Loss, medicine, Humans, Applications (stat.AP), Obesity, Low calorie diet, Inflammation, RECEPTOR, Biochemistry (medical), Gene expression profiling, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, CYTOKINE, REDUCTION, MICE, chemistry, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, inflammation, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, sense organs, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Biomarkers, Follow-Up Studies
Abstract: Context Adipose tissue (AT) transcriptome studies provide holistic pictures of adaptation to weight and related bioclinical settings changes. Objective To implement AT gene expression profiling and investigate the link between changes in bioclinical parameters and AT gene expression during 3 steps of a 2-phase dietary intervention (DI). Methods AT transcriptome profiling was obtained from sequencing 1051 samples, corresponding to 556 distinct individuals enrolled in a weight loss intervention (8-week low-calorie diet (LCD) at 800 kcal/day) followed with a 6-month ad libitum randomized DI. Transcriptome profiles obtained with QuantSeq sequencing were benchmarked against Illumina RNAseq. Reverse transcription quantitative polymerase chain reaction was used to further confirm associations. Cell specificity was assessed using freshly isolated cells and THP-1 cell line. Results During LCD, 5 modules were found, of which 3 included at least 1 bioclinical variable. Change in body mass index (BMI) connected with changes in mRNA level of genes with inflammatory response signature. In this module, change in BMI was negatively associated with changes in expression of genes encoding secreted protein (GDF15, CCL3, and SPP1). Through all phases of the DI, change in GDF15 was connected to changes in SPP1, CCL3, LIPA and CD68. Further characterization showed that these genes were specific to macrophages (with LIPA, CD68 and GDF15 expressed in anti-inflammatory macrophages) and GDF15 also expressed in preadipocytes. Conclusion Network analyses identified a novel AT feature with GDF15 upregulated with calorie restriction induced weight loss, concomitantly to macrophage markers. In AT, GDF15 was expressed in preadipocytes and macrophages where it was a hallmark of anti-inflammatory cells.
Published: 2021

9. Stability to oxidation and interfacial behavior at the air/water interface of minimally-processed versus processed walnut oil-bodies

Author: Nathalie Barouh, Jeanne Kergomard, Tim J. Wooster, Claire Bourlieu, Véronique Vié, Olivier Schafer, Pierre Villeneuve, Gilles Paboeuf, Institut de Physique de Rennes (IPR), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Ingénierie des Agro-polymères et Technologies Émergentes (UMR IATE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Démarche intégrée pour l'obtention d'aliments de qualité (UMR QualiSud), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-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), Synthèse Caractérisation Analyse de la Matière (ScanMAT), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], The authors acknowledge Carine Alcon and the imaging facility MRI (‘Montpellier Ressources Imagerie’, Montpellier, France), member of the national infrastructure France-BioImaging infrastructure supported by the French National Research Agency (ANR-10-INBS-04, «Investments for the future»)., ANR-10-INBS-0004,France-BioImaging,Développment d'une infrastructure française distribuée coordonnée(2010), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université de Montpellier (UM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut de Recherche pour le Développement (IRD)-Avignon Université (AU)-Université de La Réunion (UR)-Université de Montpellier (UM)-Institut Agro - Montpellier SupAgro, Département Performances des systèmes de production et de transformation tropicaux (Cirad-PERSYST), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Kergomard, Jeanne, and Université de Rennes (UR)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Air water interface, 01 natural sciences, Analytical Chemistry, [PHYS] Physics [physics], chemistry.chemical_compound, Walnut beverage emulsion, Traitement des aliments, Nuts, Food science, ComputingMilieux_MISCELLANEOUS, Minimalist processes, chemistry.chemical_classification, [PHYS]Physics [physics], Ellipsometry, Acide gras polyinsaturé, 04 agricultural and veterinary sciences, General Medicine, 040401 food science, Triacylglycerol storage, Émulsifiant, Oil bodies, Emulsion, Emulsions, Oxidation-Reduction, [PHYS.COND] Physics [physics]/Condensed Matter [cond-mat], Polyunsaturated fatty acid, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Juglans, Stabilité oxydative, 0404 agricultural biotechnology, Adsorption, Q02 - Traitement et conservation des produits alimentaires, Triglycéride, TBARS, Plant Oils, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Oxydation, [PHYS.COND]Physics [physics]/Condensed Matter [cond-mat], Q04 - Composition des produits alimentaires, Oxidative stability, Triglyceride, 010401 analytical chemistry, Water, Lipid Droplets, Walnut oil, Corps gras, 0104 chemical sciences, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, chemistry, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Food Science
Abstract: International audience; Oil bodies (OB), the form of triacylglycerol storage in seeds, are interesting natural assemblies for nutritional applications. In walnuts, OB contain an important amount of polyunsaturated fatty acids that could be interesting food ingredients but may be prone to oxidation. The oxidative and interfacial behavior of walnut OB, either minimally-processed or after processing, were compared with processed complex walnut juice. The good oxidative stability of minimally-processed OB over 10 days (PV ≤ 8.4 meq O2/kg, TBARS = 1.4 mmol eq MDA/kg) and of processed walnut complex matrixes over 20 days (PV ≤ 4.8 meq O2/kg, TBARS = 1.4 mmol eq MDA/kg) was evidenced. In comparison, processing of OB promoted their oxidation. The interfacial studies led to the proposition of a new model of adsorption for minimally-processed OB that will be useful to design functional emulsion or foam in which OB act as emulsifiers.
Published: 2021

10. Shear and Extensional Rheology of Linear and Branched Polybutylene Succinate Blends

Author: Rudy Valette, Anne Bergeret, Nicolas Le Moigne, Violette Bourg, Patrick Ienny, Valérie Guillard, Polymères Composites et Hybrides (PCH - IMT Mines Alès), IMT - MINES ALES (IMT - MINES ALES), Institut Mines-Télécom [Paris] (IMT)-Institut Mines-Télécom [Paris] (IMT), Durabilité des éco-Matériaux et Structures (DMS), Laboratoire de Mécanique et Génie Civil (LMGC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-IMT - MINES ALES (IMT - MINES ALES), Ingénierie des Agro-polymères et Technologies Émergentes (UMR IATE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Centre de Mise en Forme des Matériaux (CEMEF), MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), and Ceisa Packaging and the French Environment and Energy Management Agency-ADEME (n° TEZ11-26).
Subjects: Materials science, Polymers and Plastics, 02 engineering and technology, 010402 general chemistry, Branching (polymer chemistry), 01 natural sciences, Viscoelasticity, Article, molecular architecture, lcsh:QD241-441, [SPI]Engineering Sciences [physics], lcsh:Organic chemistry, Rheology, polybutylene succinate, shear rheology, Composite material, extensional rheology, Rheometry, General Chemistry, Strain hardening exponent, 021001 nanoscience & nanotechnology, 0104 chemical sciences, Polybutylene succinate, Shear (sheet metal), size-exclusion chromatography, Extrusion, biodegradable, 0210 nano-technology, long-chain branching
Abstract: International audience; The molecular architecture and rheological behavior of linear and branched polybutylene succinate blends have been investigated using size-exclusion chromatography, small-amplitude oscillatory shear and extensional rheometry, in view of their processing using cast and blown extrusion. Dynamic viscoelastic properties indicate that a higher branched polybutylene succinate amount in the blend increases the relaxation time due to an increased long-chain branching degree. Branched polybutylene succinate exhibits pronounced strain hardening under uniaxial elongation, which is known to improve processability. Under extensional flow, the 50/50 wt % blend exhibits the same behavior as linear polybutylene succinate.
Published: 2021

11. Dietary sialylated oligosaccharides in early-life may promote cognitive flexibility during development in context of obesogenic dietary intake

Author: Caroline Clouard, Stephen A. Fleming, T. Schuurman, Sietse Jan Koopmans, Jonas Hauser, I. Reimert, Wageningen University and Research [Wageningen] (WUR), Physiologie, Environnement et Génétique pour l'Animal et les Systèmes d'Elevage [Rennes] (PEGASE), AGROCAMPUS OUEST, 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Traverse Science, Inc., Wageningen Livestock Research, and Nestlé Institute of Health Sciences SA [Lausanne, Switzerland]
Subjects: cognition, Animal Nutrition, Swine, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Oligosaccharides, Medicine (miscellaneous), Prebiotic, Ecological systems theory, memory, Eating, chemistry.chemical_compound, 0302 clinical medicine, Cognition, sialyllatose, media_common, 2. Zero hunger, 0303 health sciences, Nutrition and Dietetics, [SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior, General Neuroscience, Dietary intake, Cognitive flexibility, General Medicine, Sialyllatose, Diervoeding, Early life, prebiotic, Swine, Miniature, Adaptation Physiology, Female, media_common.quotation_subject, Biology, Development, 03 medical and health sciences, 2'-Fucosyllactose, Memory, medicine, Animals, Humans, Human milk oligosaccharide, Adaptatiefysiologie, development, 030304 developmental biology, Milk, Human, Diet, chemistry, Evolutionary biology, WIAS, human activities, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030217 neurology & neurosurgery, 2′-fucosyllactose, Diversity (politics)
Abstract: International audience; Introduction: Oligosaccharides found in mammalian milk have shown the potential to alter brain development across multiple species. The diversity and concentration of these oligosaccharides is species-specific and varies greatly between individuals, thus understanding their role in cognitive development is warranted. We investigated the impact of early life dietary fucosylated/neutral or sialylated human milk oligosaccharides (HMO) on behaviours in tasks assessing anxiety, motivation, appetite, learning, and memory.Methods: Sixty-four female Göttingen minipigs were artificially reared from 2 weeks postnatal and provided milk replacers. The study used four groups: no additional oligosaccharides (Con), fucosylated and neutral oligosaccharides (FN, 4 g/L), sialylated oligosaccharides (SL, 0.68 g/L), or both FN and SL (FN + SL, 4 g/L) from 2 to 11 weeks postnatal. One reference group was sow-reared. Weaning occurred between 10 and 11 weeks postnatal, and thereafter an obesogenic diet was provided. Behavioral tasks were conducted over three periods: 1) 0–11 weeks; 2) 16–29 weeks; 3) 39–45 weeks. Tasks included a spatial holeboard task, open field task, exposure to a novel object, runway task, single-feed task, and home pen behaviour observation.Results: In the holeboard, the SL group demonstrated improved reference memory during reversal trials between 16-29 weeks. All groups demonstrated equivalent behavior in open field, novel object, runway, and single-feed tasks, as well as in their home pens (Ps > 0.05).Discussion: These results suggest that early life dietary intake of sialylated oligosaccharides may provide an improvement to cognition during the equivalent developmental stage of adolescence.
Published: 2021

12. Analysis of dietary patterns and nutritional adequacy in lactating women : a multicentre European cohort (ATLAS study)

Author: Magnus Domellöf, Mathilde Fleith, Kirsti Haaland, Massimo Agosti, Giovanna Marchini, Claude Billeaud, Frank Thielecke, Jean-Charles Picaud, Dantong Wang, Tinu Mary Samuel, Carlos Antonio De Castro, Maria Jose Costeira, Cecilia Martínez-Costa, Myriam C. Afeiche, Mireille Vanapee, Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Swiss Distance University of Applied Sciences [Regensdorf-Zurich, Switzerland] (SDUAS), T2 Bene Ltd [Allschwil, Switzerland], Universitat de València (UV), Oslo University Hospital [Oslo], Karolinska University Hospital [Stockholm], Ospedale del Ponte [Varese, Italy], Umeå University, Instituto de Investigação em Ciências da Vida e Saúde [Braga, Portugal] (Escola de Ciências da Saúde), Universidade do Minho, CHU de Bordeaux Pellegrin [Bordeaux], Karolinska Institutet [Stockholm], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Universidade do Minho = University of Minho [Braga], and CarMeN, laboratoire
Subjects: Vitamin, 030309 nutrition & dietetics, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Nutritional Status, 030209 endocrinology & metabolism, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Cluster analysis, Multicentre European cohort, Environmental health, Pantothenic acid, Vitamin D and neurology, Medicine, Humans, Lactation, Longitudinal Studies, Dietary Reference Values, 2. Zero hunger, 0303 health sciences, Nutrition and Dietetics, Vitamin C, Milk, Human, Nutrition adequacy, business.industry, Dietary Surveys and Nutritional Epidemiology, Infant, Food Patterns, Diet, [SDV] Life Sciences [q-bio], Europe, Näringslära, Breast Feeding, chemistry, Dietary Reference Intake, Cohort, Lactating mothers, Female, business, Food Science, Research Article
Abstract: Eating habits of lactating women can influence the nutrient composition of human milk, which in turn influences nutrient intake of breastfed infants. The aim of the present study was to identify food patterns and nutritional adequacy among lactating women in Europe. Data from a multicentre European longitudinal cohort (ATLAS study) were analysed to identify dietary patterns using cluster analysis. Dietary information from 180 lactating women was obtained using 3-d food diaries over the first 4 months of lactation. Four dietary patterns were identified: ‘vege-oils’, ‘fish-poultry’, ‘confectionery-salads’ and ‘mixed dishes’. Nutrition adequacy was not significantly different between clusters, but the ‘vege-oils’ cluster tended to yield the highest nutrition adequacy measured by Mean Adequacy Ratio. Compared with European dietary reference values (DRVs) for lactating women, women in all clusters had inadequate intakes of energy, pantothenic acid, folate, vitamin C, vitamin A, vitamin D, zinc, iodine, potassium and linoleic acid. Adequate intake for fibre and α-linolenic acid was only achieved in the ‘vege-oils’ cluster. Overall, fat intake was above DRVs. The present study showed that various dietary patterns do not adequately supply all nutrients, indicating a need to promote overall healthy dietary habits for European lactating women.
Published: 2021

13. Deciphering the Chemistry of Cultural Heritage: Targeting Material Properties by Coupling Spectral Imaging with Image Analysis

Author: Étienne Anheim, Loïc Bertrand, Pierre Gueriau, Mathieu Thoury, Serge X. Cohen, Photophysique et Photochimie Supramoléculaires et Macromoléculaires (PPSM), Institut de Chimie du CNRS (INC)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay), Institut photonique d'analyse non-destructive européen des matériaux anciens (IPANEMA), Muséum national d'Histoire naturelle (MNHN)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Centre National de la Recherche Scientifique (CNRS)-Ministère de la Culture (MC), Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Centre de Recherches Historiques (CRH), École des hautes études en sciences sociales (EHESS)-Centre National de la Recherche Scientifique (CNRS), and We thank Barbara Berrie (National Gallery of Art, Washington, D.C., U.S.) and Agnès Desolneux (Centre Borelli, ENS Paris-Saclay, CNRS) for their careful rereading of our manuscript. The authors are particularly grateful to the large number of colleagues with whom we have discussed these aspects over many years of common work and interaction. Our very special thanks go to Marie-Angélique Languille (today at the Centre de Recherche sur la Conservation des Collections, Paris) and Sophie David (PPSM). We thank all of our coauthors from the papers discussed and the many colleagues with whom we have discussed these ideas, including Demetrios Anglos, Julie Arslanoglu, Bernadette Bensaude-Vincent, Uwe Bergmann, Barbara Berrie, Catherine Brechignac, Gilles Celeux, Antoine Chambaz, Pierre Chastang, Cynthia Colmellere, Marie Cornu, Jean-Paul Demoule, Agnès Desolneux, Jean-Philippe Échard, Douglas Galante, Pierre Galtier, Claire Gervais, Denis Gratias, Agnès Grimaud, Charlotte Guichard, Ineke Joosten, Katrien Keune, Andrew King, Bertrand Lavédrine, Pierre Laszlo, Erwan Le Pennec, Pierre Levitz, Alain Lusson, Lara Maldanis, Pascal Massard, Cristian Mocuta, Lionel Moisan, Emmanuel (Manolis) Pantos, André Rassat, Matthieu Réfrégiers, Luc Robbiola, Laurent Romary, Isabelle Rouget, Jean-Pascal Rueff, Solenn Réguer, Clément Sanchez, Sebastian Schoeder, Marika Spring, Maartje Stols-Witlox, Matija Strlic, Caroline Tokarski, Edward Vicenzi, Laurence de Viguerie, Kees van der Beek, Robert van Langh, Philippe Walter, Sam Webb, and many friends, students, and colleagues. L.B. acknowledges the support of the Fondation des Treilles and its wonderful team for the organization of two seminars (in 2013 and 2014) that enabled the scope of this research program to be critically defined. The construction of the IPANEMA laboratory was funded by a CPER grant from the French Ministère de la recherche, de l’enseignement supérieur et de l’innovation and Région Île-de-France.
Subjects: medicine.medical_specialty, Data processing, Materials science, 010405 organic chemistry, Chemistry, media_common.quotation_subject, Hyperspectral imaging, General Medicine, General Chemistry, Ambiguity, 010402 general chemistry, 01 natural sciences, Data science, 0104 chemical sciences, Spectral imaging, Characterization (materials science), Cultural heritage, Identification (information), medicine, [CHIM]Chemical Sciences, Spatial analysis, media_common
Abstract: International audience; ConspectusThe chemical study of materials from natural history and cultural heritage, which provide information for art history, archeology, or paleontology, presents a series of specific challenges. The complexity of these ancient and historical materials, which are chemically heterogeneous, the product of alteration processes, and inherently not reproducible, is a major obstacle to a thorough understanding of their making and long-term behavior (e.g., fossilization). These challenges required the development of methodologies and instruments coupling imaging and data processing approaches that are optimized for the specific properties of the materials. This Account discusses how these characteristics not only constrain their study but also open up specific innovative avenues for providing key historical information. Synchrotron methods have extensively been used since the late 1990s to study heritage objects, in particular for their potential to provide speciation information from excitation spectroscopies and to image complex heritage objects and samples in two and three dimensions at high resolution. We examine in practice how the identification of key intrinsic chemical specificities has offered fertile ground for the development of novel synchrotron approaches allowing a better stochastic description of the properties of ancient and historical materials. These developments encompass three main aspects: (1) The multiscale heterogeneity of these materials can provide an essential source of information in the development of probes targeting their multiple scales of homogeneity. (2) Chemical alteration can be described in many ways, e.g., by segmenting datasets in a semiquantitative way to jointly inform morphological and chemical transformation pathways. (3) The intrinsic individuality of chemical signatures in artifacts triggers the development of specific strategies, such as those focusing on weak signal detection. We propose a rereading of the advent of these new methodologies for analysis and characterization and examine how they have led to innovative strategies combining materials science, instrument development, history, and data science. In particular, we show that spectral imaging and the search for correlations in image datasets have provided a powerful way to address what archeologists have called the uncertainty and ambiguity of the material record. This approach has implications beyond synchrotron techniques and extends in particular to a series of rapidly developing approaches that couple spectral and spatial information, as in hyperspectral imaging and spatially resolved mass spectrometry. The preeminence of correlations holds promise for the future development of machine learning methods for processing data on historical objects. Beyond heritage, these developments are an original source of inspiration for the study of materials in many related fields, such as environmental, geochemical, or life sciences, which deal with systems whose alteration and heterogeneity cannot be neglected.
Published: 2021

14. Oxidative and interfacial behavior of oil bodies from walnut

Author: Jeanne Kergomard, Vié, V., Paboeuf, G., Nathalie Barouh, Bruno Barea, Villeneuve, Pierre P., Olivier Schafer, Wooster, Tim J., Claire Bourlieu, Institut de Physique de Rennes (IPR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Ingénierie des Agro-polymères et Technologies Émergentes (UMR IATE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université de Montpellier (UM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - 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), Département Performances des systèmes de production et de transformation tropicaux (Cirad-PERSYST), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Société Française pour l'étude des Lipides (SFEL), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université de Montpellier (UM)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), and 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: [PHYS]Physics [physics], [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], [SDV.IDA]Life Sciences [q-bio]/Food engineering, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [PHYS.COND.CM-SCM]Physics [physics]/Condensed Matter [cond-mat]/Soft Condensed Matter [cond-mat.soft], ComputingMilieux_MISCELLANEOUS
Abstract: National audience
Published: 2020

15. Exploration of human cerebrospinal fluid A large proteome dataset revealed by trapped ion mobility time-of-flight mass spectrometry

Author: Charlotte Macron, Michael Affolter, Charles Pineau, Loïc Dayon, Antonio Núñez Galindo, Régis Lavigne, Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], 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 ), Proteomics Core Facility (Protim), Université de Rennes (UR)-Plateforme Génomique Santé Biogenouest®, Ecole Polytechnique Fédérale de Lausanne (EPFL), Jonchère, Laurent, 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 ), Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Plateforme Génomique Santé Biogenouest®
Subjects: Proteomics, workflow, [SDV]Life Sciences [q-bio], Shotgun, Computational biology, Mass spectrometry, lcsh:Computer applications to medicine. Medical informatics, Tandem mass spectrum, 03 medical and health sciences, 0302 clinical medicine, Cerebrospinal fluid, LC-MS/MS, lcsh:Science (General), 030304 developmental biology, 0303 health sciences, Multidisciplinary, Chemistry, Tryptic peptide, quantification, [SDV] Life Sciences [q-bio], Large-scale proteome, Proteome, lcsh:R858-859.7, Time-of-flight mass spectrometry, 030217 neurology & neurosurgery, lcsh:Q1-390
Abstract: Cerebrospinal fluid (CSF) is a biofluid in direct contact with the brain and as such constitutes a sample of choice in neu-rological disorder research, including neurodegenerative dis-eases such as Alzheimer or Parkinson. Human CSF has still been less studied using proteomic technologies compared to other biological fluids such as blood plasma or serum. In this work, a pool of "normal" human CSF samples was analysed using a shotgun proteomic workflow that combined removal of highly abundant proteins by immunoaffinity depletion and isoelectric focussing fractionation of tryptic peptides to alle-viate the complexity of the biofluid. The resulting 24 frac-tions were analysed using liquid chromatography coupled to a high-resolution and high-accuracy timsTOF Pro mass spec-trometer. This state-of-the-art mass spectrometry-based pro-teomic workflow allowed the identification of 3'174 proteins in CSF. The dataset reported herein completes the pool of the most comprehensive human CSF proteomes obtained so far. An overview of the identified proteins is provided based on gene ontology annotation. Mass and tandem mass spectra are made available as a possible starting point for further studies exploring the human CSF proteome. (c) 2020 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license. ( http://creativecommons.org/licenses/by/4.0/ )
Published: 2020

16. Collective stiffening of soft hair assemblies

Author: Benjamin Le Révérend, Eric Lauga, Alexis Prevost, Elie Wandersman, Jean-Baptiste Thomazo, Laboratoire Jean Perrin (LJP), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), 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), Department of Applied Mathematics and Theoretical Physics (DAMTP), University of Cambridge [UK] (CAM), and Nestlé Institute of Health Sciences SA [Lausanne, Switzerland]
Subjects: Materials science, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Mechanical Phenomena, FOS: Physical sciences, Condensed Matter - Soft Condensed Matter, 01 natural sciences, 010305 fluids & plasmas, Biological Physics, [MATH.MATH-MP]Mathematics [math]/Mathematical Physics [math-ph], Deflection (engineering), 0103 physical sciences, Phenomenological model, otorhinolaryngologic diseases, Shear stress, 010306 general physics, Porosity, ComputingMilieux_MISCELLANEOUS, integumentary system, Polymers & Soft Matter, Fluid Dynamics, Mechanics, Biomechanical Phenomena, Stiffening, Soft Condensed Matter (cond-mat.soft), sense organs, Shear Strength, Porous medium, Shear flow, [PHYS.COND.CM-SCM]Physics [physics]/Condensed Matter [cond-mat]/Soft Condensed Matter [cond-mat.soft], Hair
Abstract: Many living systems use assemblies of soft and slender structures whose deflections allow them to mechanically probe their immediate environment. In this work, we study the collective response of artificial soft hair assemblies to a shear flow by imaging their deflections. At all hair densities, the deflection is found to be proportional to the local shear stress with a proportionality factor that decreases with density. The measured collective stiffening of hairs is modeled both with a microscopic elastohydrodynamic model that takes into account long range hydrodynamic hair-hair interactions and a phenomenological model that treats the hair assemblies as an effective porous medium. While the microscopic model is in reasonable agreement with the experiments at low hair density, the phenomenological model is found to be predictive across the entire density range., Comment: 5 pages, 3 figures
Published: 2020

17. Integrative phenotyping of glycemic responders upon clinical weight loss using multi-omics

Author: Ellen E. Blaak, Anirikh Chakrabarti, Mojgan Masoodi, Nathalie Viguerie, Armand Valsesia, Jörg Hager, Dominique Langin, Arne Astrup, Wim H. M. Saris, Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), 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), Université Fédérale Toulouse Midi-Pyrénées, Laboratory of Clinical Biochemistry [Toulouse], CHU Toulouse [Toulouse], Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], University of Copenhagen = Københavns Universitet (KU), Bern University Hospital [Berne] (Inselspital), The study was founded by the European Commission, Food Quality and Safety Priority of the Sixth Framework Program (FP6-2005-513946), and Nestlé Institute of Health Sciences., Laboratoire de Biochimie [CHU Toulouse], Institut Fédératif de Biologie (IFB), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Pôle Biologie [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), University of Copenhagen = Københavns Universitet (UCPH), Bodescot, Myriam, RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, and Humane Biologie
Subjects: 0301 basic medicine, Proteomics, Metabolic disorders, PROTEIN, Physiology, Adipose tissue, Ketone Bodies, CALORIC RESTRICTION, 0302 clinical medicine, Endocrinology, Weight loss, Medicine, 610 Medicine & health, INSULIN-RESISTANCE, Multidisciplinary, Area under the curve, Endocrine system and metabolic diseases, Genomics, Lipids, ADIPOSE-TISSUE, Phenotype, Cardiovascular diseases, Adipose Tissue, VISCERAL FAT, OBESITY, Area Under Curve, Body Composition, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine.symptom, Diet, Reducing, Fatty Acid Elongases, Science, Down-Regulation, 030209 endocrinology & metabolism, Intra-Abdominal Fat, APOLIPOPROTEIN-E, Article, 03 medical and health sciences, Insulin resistance, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], Weight Loss, Humans, DE-NOVO LIPOGENESIS, Glycemic, business.industry, medicine.disease, Omics, Obesity, Confidence interval, Computational biology and bioinformatics, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, 030104 developmental biology, ROC Curve, RISK-FACTORS, GLUCOSE-TOLERANCE, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Biomarkers
Abstract: Weight loss aims to improve glycemic control in obese but strong variability is observed. Using a multi-omics approach, we investigated differences between 174 responders and 201 non-responders, that had lost >8% body weight following a low-caloric diet (LCD, 800 kcal/d for 8 weeks). The two groups were comparable at baseline for body composition, glycemic control, adipose tissue transcriptomics and plasma ketone bodies. But they differed significantly in their response to LCD, including improvements in visceral fat, overall insulin resistance (IR) and tissue-specific IR. Transcriptomics analyses found down-regulation in key lipogenic genes (e.g. SCD, ELOVL5) in responders relative to non-responders; metabolomics showed increase in ketone bodies; while proteomics revealed differences in lipoproteins. Findings were consistent between genders; with women displaying smaller improvements owing to a better baseline metabolic condition. Integrative analyses identified a plasma omics model that was able to predict non-responders with strong performance (on a testing dataset, the Receiving Operating Curve Area Under the Curve (ROC AUC) was 75% with 95% Confidence Intervals (CI) [67%, 83%]). This model was based on baseline parameters without the need for intrusive measurements and outperformed clinical models (p = 0.00075, with a +14% difference on the ROC AUCs). Our approach document differences between responders and non-responders, with strong contributions from liver and adipose tissues. Differences may be due to de novo lipogenesis, keto-metabolism and lipoprotein metabolism. These findings are useful for clinical practice to better characterize non-responders both prior and during weight loss.
Published: 2020

18. Human milk oligosaccharides alleviate stress-induced visceral hypersensitivity and associated microbiota dysbiosis

Author: Julien Chevalier, Gabriela Bergonzelli, Guillaume Jacot, María Vicario, Laurent Favre, Léa Siegwald, Andreas Rytz, Helene Eutamene, Valérie Tondereau, Vassilia Theodorou, Laurent Ferrier, Clara Lucia Garcia-Rodenas, Andrea M. Marquard, Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Clinical Microbiomics, and Société des Produits Nestlé.
Subjects: Male, Abdominal pain, medicine.drug_class, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Antibiotics, microbiome, Oligosaccharides, Distension, Gut flora, Biochemistry, antibiotics, Feces, Mice, 03 medical and health sciences, 0302 clinical medicine, medicine, Animals, Humans, Microbiome, metagenomic, Molecular Biology, 030304 developmental biology, HMOs, 0303 health sciences, Nutrition and Dietetics, Bacteria, Milk, Human, biology, business.industry, medicine.disease, biology.organism_classification, Abdominal Pain, Gastrointestinal Microbiome, Mice, Inbred C57BL, Nociception, Immunology, Dysbiosis, 030211 gastroenterology & hepatology, medicine.symptom, chronic psychological stress, business, Stress, Psychological
Abstract: International audience; Pain-related functional gastrointestinal disorders (FGIDs) are characterized by visceral hypersensitivity (VHS) associated with alterations in the microbiota-gut-brain axis. Since human milk oligosaccharides (HMOs) modulate microbiota, gut and brain, we investigated whether HMOs impact VHS and explored the role of gut microbiota. To induce VHS, C57BL/6JRj mice received hourly water avoidance stress (WAS) sessions for 10 days, or antibiotics (ATB) for 12 days. Challenged and unchallenged (Sham) animals were fed AIN93M diet (Cont) or AIN93M containing 1% of a 6-HMO mix (HMO6). VHS was assessed by monitoring the visceromotor response to colorectal distension. Fecal microbiome was analyzed by shotgun metagenomics. The effect of HMO6 sub-blends on VHS and nociceptive pathways was further tested using the WAS model. In mice fed Cont, WAS and ATB increased the visceromotor response to distension. HMO6 decreased WAS-mediated electromyographic rise at most distension volumes and overall Area Under Curve (AUC=6.12±0.50 in WAS-HMO6 vs 9.46±0.50 in WAS-Cont; p
Published: 2022

19. Subclinical Mastitis in a European Multicenter Cohort: Prevalence, Impact on Human Milk (HM) Composition, and Association with Infant HM Intake and Growth

Author: Magnus Domellöf, Jean-Charles Picaud, Isam Al-Jashi, Michael Affolter, Kirsti Haaland, Eurídice Castañeda-Gutiérrez, Silvia Maria Stoicescu, Maria Jose Costeira, Sagar K. Thakkar, Stéphane Dubascoux, Giovanna Marchini, Tom Stiris, Carlos Antonio De Castro, Massimo Agosti, Maria Gorett Silva, Mireilla Vanpee, Cecilia Martínez-Costa, Francesca Giuffrida, Almerinda Barroso Pereira, Claude Billeaud, Irma Silva-Zolezzi, Tinu Mary Samuel, Thameur Rakza, Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], CHU de Bordeaux Pellegrin [Bordeaux], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), AUTRES, Medicine Faculty, Titu Maiorescu University, City Bucharest, Romania., Hospital de São João [Porto], Karolinska University Hospital [Stockholm], Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Oslo University Hospital [Oslo], Polizu Hospital, Universitat de València (UV), and Umeå University
Subjects: Adult, 0301 basic medicine, Longitudinal study, [SDV]Life Sciences [q-bio], Mammary gland, Physiology, lcsh:TX341-641, Mastitis, Article, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Subclinical mastitis, subclinical mastitis, Minerals, 030219 obstetrics & reproductive medicine, 030109 nutrition & dietetics, Nutrition and Dietetics, Milk, Human, business.industry, fungi, Infant, Newborn, longitudinal study, Infant, human milk, Feeding Behavior, European population, medicine.disease, Trace Elements, 3. Good health, Europe, Näringslära, Breast Feeding, medicine.anatomical_structure, Cohort, milk macronutrients, Female, business, lcsh:Nutrition. Foods and food supply, Food Science
Abstract: Background: Subclinical mastitis (SCM) is an inflammatory condition of the mammary gland. We examined the effects of SCM on human milk (HM) composition, infant growth, and HM intake in a mother&ndash, infant cohort from seven European countries. Methods: HM samples were obtained from 305 mothers at 2, 17, 30, 60, 90, and 120 days postpartum. SCM status was assessed using HM Sodium (Na): Potassium (K) ratio &gt, 0.6. Levels of different macro- and micronutrients were analyzed in HM. Results: SCM prevalence in the first month of lactation was 35.4%. Mean gestational age at delivery was lower and birth by C-section higher in SCM mothers (p &le, 0.001). HM concentrations of lactose, DHA, linolenic acid, calcium, and phosphorous (p &lt, 0.05 for all) was lower, while total protein, alpha-lactalbumin, lactoferrin, albumin, arachidonic acid to DHA ratio, n-6 to n-3 ratio and minerals (iron, selenium, manganese, zinc, and copper) were higher (p &lt, 0.001 for all) in mothers with SCM. There were no differences in infant growth and HM intake between non-SCM and SCM groups. Conclusion: We document, for the first time, in a large European standardized and longitudinal study, a high prevalence of SCM in early lactation and demonstrate that SCM is associated with significant changes in the macro- and micronutrient composition of HM. Future studies exploring the relation of SCM with breastfeeding behaviors and developmental outcomes are warranted.
Published: 2019
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20. Stem cells and the circadian clock

Author: Thomas Dickmeis, Nicolas Diotel, Benjamin D. Weger, Anne Claire Dorsemans, Meltem Weger, Univ, Réunion, University of Birmingham [Birmingham], Diabète athérothrombose et thérapies Réunion Océan Indien (DéTROI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de La Réunion (UR), Karlsruhe Institute of Technology (KIT), and Nestlé Institute of Health Sciences SA [Lausanne, Switzerland]
Subjects: Life sciences, biology, 0301 basic medicine, medicine.medical_specialty, Circadian clock, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], Development, Biology, Adult neurogenesis, Models, Biological, 03 medical and health sciences, Circadian Clocks, ddc:570, Internal medicine, [SDV.BDD] Life Sciences [q-bio]/Development Biology, [SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], medicine, Animals, Humans, Circadian rhythm, [SDV.BDD]Life Sciences [q-bio]/Development Biology, Molecular Biology, Stem cell, Vertebrate, Stem Cells, Neurogenesis, Cell migration, Cell Biology, Hair follicle, Embryonic stem cell, Circadian Rhythm, Cell biology, 030104 developmental biology, Endocrinology, medicine.anatomical_structure, Developmental Biology, Adult stem cell
Abstract: International audience; The circadian timing system is a complex biological network of interacting circadian clocks that regulates 24 h rhythms of behavioral and physiological processes. One intriguing observation is that stem cell homeostasis is subject to circadian clock regulation. Rhythmic oscillations have been observed in a variety of embryonic and adult stem cell dependent processes, such as hematopoietic progenitor cell migration, the hair follicle cycle, bone remodeling, regenerative myogenesis and neurogenesis. This review aims to discuss the nature of the circadian clock in embryonic stem cells and how it changes during differentiation. Furthermore, it will examine how the circadian clock contributes to adult stem cell function in different tissues of the body with an emphasis on the brain and adult neurogenesis.
Published: 2017

21. Nutrition for the ageing brain: Towards evidence for an optimal diet

Author: Robert J. Williams, Robert Perneczky, Pascale Barberger-Gateau, Hugh Perry, Robin S.B. Williams, Maria Camprubi-Robles, Keith Wesnes, Jeroen Schuermans, Robert Clarke, Sandrine Thuret, Laura Caberlotto, Cristina Andres-Lacueva, Claudine Manach, John W.C. Sijben, Jeremy P. E. Spencer, Anne Marie Roussel, Gene L. Bowman, Sophie Miquel-Kergoat, Ondine van de Rest, María J. Ramírez, Ellen S. Mitchell, Eef Hogervorst, Amanda J. Kiliaan, Maurits Vandewoude, Ugo Lucca, Diána Bánáti, David Vauzour, Anne Marie Minihane, Norwich Medical School, University of East Anglia [Norwich] (UEA), Abbot Nutrition R&D, Wrigley, University of Barcelona, International Life Sciences Institute Europe (ILSI Europe), U 897, Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB), Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Centre for Computational and Systems Biology (COSBI), Università degli Studi di Trento (UNITN), University of Oxford, Loughborough University, Radboud University Medical Center [Nijmegen], Istituto di Ricerce Farmacologiche Mario Negri, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Imperial College London, University of Southampton, Université Joseph Fourier - Grenoble 1 (UJF), Nutricia Research, University of Reading (UOR), Maurice Wohl Clinical Neuroscience Institut, King‘s College London, King's College Hospital (KCH), Wageningen University and Research [Wageningen] (WUR), University of Antwerp (UA), Wesnes Cognition Ltd, Department of Psychology [Sheffield], University of Sheffield [Sheffield], Centre for Human Psychopharmacology, Swinburne University, Medicinal Plant Research Group, Newcastle University, University of Bath [Bath], Abbott Nutrition R&D, University of East Anglia, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Wageningen University and Research Center (WUR), University of Antwerp, and University of Oxford [Oxford]
Subjects: 0301 basic medicine, Gerontology, MILD COGNITIVE IMPAIRMENT, Aging, Geriatrics & Gerontology, Alzheimer`s disease Donders Center for Medical Neuroscience [Radboudumc 1], Physiology, Fisiologia patològica, Cognitive decline, B400, Biochemistry, Nutritional requirements, 0302 clinical medicine, Cognition, Neuroinflammation, approche nutritionnelle, CARDIOVASCULAR RISK-FACTORS, Psychology, méthode de prévention, Cervell, Pathological physiology, senior citizens, Dietoteràpia, education.field_of_study, Preventive diet, Cognitive ageing, Envelliment cerebral, [SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology, Brain, ALZHEIMERS ASSOCIATION WORKGROUPS, Neuroprotection, 3. Good health, AMYLOID PRECURSOR PROTEIN, Neurology, SPATIAL WORKING-MEMORY, Cognició, Aging brain, Diet, Healthy, Alzheimer's disease, Nutritive Value, Life Sciences & Biomedicine, Biotechnology, Cognition disorders, RANDOMIZED CONTROLLED-TRIALS, MULTI-NUTRIENT DIET, Population, Fisiologia, Affect (psychology), Trastorns de la cognició, personne âgée, 03 medical and health sciences, POSITRON-EMISSION-TOMOGRAPHY, medicine, Humans, NITRIC-OXIDE SYNTHASE, education, Biology, Molecular Biology, maladie neurodégénérative, VLAG, Global Nutrition, Wereldvoeding, Science & Technology, Diet therapy, Nutritional Requirements, Requeriments nutricionals, 0601 Biochemistry And Cell Biology, 1103 Clinical Sciences, Cell Biology, medicine.disease, C800, Ageing, 030104 developmental biology, Clinical research, Psicologia, Nerve Degeneration, Human medicine, Cognition Disorders, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, FLAVANOL-RICH COCOA, 030217 neurology & neurosurgery
Abstract: The workshop 'Nutrition for the Ageing Brain: Towards Evidence of an Optimal Diet' was organized with funds from the ILSI Europe Nutrition and Mental Performance Task Force. Industry members of this task force are listed on the ILSI Europe website at www.ilsi.eu. For further information about ILSI Europe, please email or call +32 2 771 00 14. This review was prepared taken into account the presentations at the workshop mentioned in the abstract and was conducted by an expert group of ILSI Europe. This publication was coordinated by Mr Jeroen Schuermans, Scientific Project Manager at ILSI Europe during the proceedings process. The authors would like to acknowledge Ms Catherine Collins, Ms Lilou van Lieshout and Dr Lucie Geurts for the finalisation and submission of this manuscript; As people age they become increasingly susceptible to chronic and extremely debilitating brain diseases. The precise cause of the neuronal degeneration underlying these disorders, and indeed normal brain ageing remains however elusive. Considering the limits of existing preventive methods, there is a desire to develop effective and safe strategies. Growing preclinical and clinical research in healthy individuals or at the early stage of cognitive decline has demonstrated the beneficial impact of nutrition on cognitive functions. The present review is the most recent in a series produced by the Nutrition and Mental Performance Task Force under the auspice of the International Life Sciences Institute Europe (ILSI Europe). The latest scientific advances specific to how dietary nutrients and non-nutrient may affect cognitive ageing are presented. Furthermore, several key points related to mechanisms contributing to brain ageing, pathological conditions affecting brain function, and brain biomarkers are also discussed. Overall, findings are inconsistent and fragmented and more research is warranted to determine the underlying mechanisms and to establish dose-response relationships for optimal brain maintenance in different population subgroups. Such approaches are likely to provide the necessary evidence to develop research portfolios that will inform about new dietary recommendations on how to prevent cognitive decline
Published: 2017

22. AMPK promotes induction of the tumor suppressor FLCN through activation of TFEB independently of mTOR

Author: Sylviane Metairon, Gregory Lefebvre, Maria Deak, Alice Parisi, Gabriele Civiletto, Philipp Gut, Patrick Descombes, Benoit Viollet, Caterina Collodet, Frederic Raymond, Marc Foretz, Kei Sakamoto, Laurent Bultot, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Catholique de Louvain (UCL), Genomics, Biotec, Dresden, Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Dept Bioanalyt Sci, Nestlé Suisse, Nestlé Research, Genomics Platform, University of Geneva [Switzerland]-National Center of Competence in Research ‘Frontiers in Genetics', Advanced Institute of Industrial Technology, Université Catholique de Louvain = Catholic University of Louvain (UCL), and UCL - SSS/IREC/CARD - Pôle de recherche cardiovasculaire
Subjects: 0301 basic medicine, folliculin interacting protein, Active Transport, Cell Nucleus, AICAR, TFE3, folliculin, AMP-Activated Protein Kinases, Biology, Biochemistry, Mice, 03 medical and health sciences, 0302 clinical medicine, Proto-Oncogene Proteins, Gene expression, Genetics, Animals, Phosphorylation, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Folliculin, Molecular Biology, Transcription factor, Zebrafish, Cells, Cultured, PI3K/AKT/mTOR pathway, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors, Research, Gene Expression Profiling, TOR Serine-Threonine Kinases, Tumor Suppressor Proteins, AMPK, Birt-Hogg-Dubé syndrome, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, Ribonucleotides, [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism, Aminoimidazole Carboxamide, biology.organism_classification, Cell biology, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], 030104 developmental biology, Hepatocytes, TFEB, 030217 neurology & neurosurgery, Biotechnology
Abstract: International audience; AMPK is a central regulator of energy homeostasis. AMPK not only elicits acute metabolic responses but also promotes metabolic reprogramming and adaptations in the long-term through regulation of specific transcription factors and coactivators. We performed a whole-genome transcriptome profiling in wild-type (WT) and AMPK-deficient mouse embryonic fibroblasts (MEFs) and primary hepatocytes that had been treated with 2 distinct classes of small-molecule AMPK activators. We identified unique compound-dependent gene expression signatures and several AMPK-regulated genes, including folliculin (Flcn), which encodes the tumor suppressor FLCN. Bioinformatics analysis highlighted the lysosomal pathway and the associated transcription factor EB (TFEB) as a key transcriptional mediator responsible for AMPK responses. AMPK-induced Flcn expression was abolished in MEFs lacking TFEB and transcription factor E3, 2 transcription factors with partially redundant function; additionally, the promoter activity of Flcn was profoundly reduced when its putative TFEB-binding site was mutated. The AMPK-TFEB-FLCN axis is conserved across species; swimming exercise in WT zebrafish induced Flcn expression in muscle, which was significantly reduced in AMPK-deficient zebrafish. Mechanistically, we have found that AMPK promotes dephosphorylation and nuclear localization of TFEB independently of mammalian target of rapamycin activity. Collectively, we identified the novel AMPK-TFEB-FLCN axis, which may function as a key cascade for cellular and metabolic adaptations.-Collodet, C., Foretz, M., Deak, M., Bultot, L., Metairon, S., Viollet, B., Lefebvre, G., Raymond, F., Parisi, A., Civiletto, G., Gut, P., Descombes, P., Sakamoto, K. AMPK promotes induction of the tumor suppressor FLCN through activation of TFEB independently of mTOR.
Published: 2019

23. Development and evaluation of a genome‐wide Coffee 8.5K SNP array and its application for high‐density genetic mapping and for investigating the origin of Coffea arabica L

Author: Christine Tranchant-Dubreuil, Patrick Descombes, Steven Janssens, C. Kiwuka, Pascal Musoli, Valérie Poncet, Piet Stoffelen, Sylviane Metairon, Clara Revel, Coralie Fournier, Alexandre de Kochko, Marie Pégard, Maud Lepelley, Hyacinthe Legnaté, Manon Coulée, Rémi Tournebize, Laurence Bellanger, Ucu Sumirat, João Ferreira da Costa Neto, Vimel Rattina, O. Darracq, Dominique Crouzillat, Jean Léon Kambale, Virginie Mérot-L’Anthoëne, Diversité, adaptation, développement des plantes (UMR DIADE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Botanic Garden Meise, Wageningen University and Research [Wageningen] (WUR), Centre National de la Recherche Agronomique - CNRA (IVORY COAST), Université de Kisangani, This project was partially supported by the Agropolis Foundationunder References ID 1002-009 and ID 1402-003 through the «Investissements d’avenir » program (Labex Agro:ANR-10-LABX0001-01), in the framework of I-SITE MUSE (ANR-16-IDEX-0006)., ANR-10-LABX-0001,AGRO,Agricultural Sciences for sustainable Development(2010), ANR-16-IDEX-0006,MUSE,MUSE(2016), and Meise Botanic Garden [Belgium] (Plantentuin)
Subjects: 0106 biological sciences, 0301 basic medicine, Genetic Markers, C. eugenioides, Canephora, single‐nucleotide polymorphism, Single-nucleotide polymorphism, Coffea, Plant Science, Coffea canephora, 01 natural sciences, Polymorphism, Single Nucleotide, [SDV.GEN.GPL]Life Sciences [q-bio]/Genetics/Plants genetics, 03 medical and health sciences, Genetic map, Gene mapping, SNP, genetic map, Uganda, Genetic variability, Research Articles, C. canephora, 2. Zero hunger, Genetics, biology, Coffea arabica origin, Coffea arabica, Chromosome Mapping, single-nucleotide polymorphism, biology.organism_classification, [SDV.BV.AP]Life Sciences [q-bio]/Vegetal Biology/Plant breeding, 030104 developmental biology, Centre for Crop Systems Analysis, Crop and Weed Ecology, SNP array, Agronomy and Crop Science, Genome, Plant, 010606 plant biology & botany, Biotechnology, Research Article
Abstract: International audience; Coffee species such as Coffea canephora P. (Robusta) and C. arabica L. (Arabica) are important cash crops in tropical regions around the world. C. arabica is an allotetraploid (2n = 4x = 44) originating from a hybridization event of the two diploid species C. canephora and C. eugenioides (2n = 2x = 22). Interestingly, these progenitor species harbour a greater level of genetic variability and are an important source of genes to broaden the narrow Arabica genetic base. Here, we describe the development, evaluation and use of a single-nucleotide polymorphism (SNP) array for coffee trees. A total of 8580 unique and informative SNPs were selected from C. canephora and C. arabica sequencing data, with 40% of the SNP located in annotated genes. In particular, this array contains 227 markers associated to 149 genes and traits of agronomic importance. Among these, 7065 SNPs (~82.3%) were scorable and evenly distributed over the genome with a mean distance of 54.4 Kb between markers. With this array, we improved the Robusta high-density genetic map by adding 1307 SNP markers, whereas 945 SNPs were found segregating in the Arabica mapping progeny. A panel of C. canephora accessions was successfully discriminated and over 70% of the SNP markers were transferable across the three species. Furthermore, the canephora-derived subgenome of C. arabica was shown to be more closely related to C. canephora accessions from northern Uganda than to other current populations. These validated SNP markers and high-density genetic maps will be useful to molecular genetics and for innovative approaches in coffee breeding.
Published: 2019

24. Perspectives on ethnic and racial disparities in Alzheimer's disease and related dementias: Update and areas of immediate need

Author: Jennifer J. Manly, Ralph N. Martins, Lon S. Schneider, Kerry Kilborn, Yakeel T. Quiroz, Scott M. Hofer, Robert A. Rissman, Octavio A. Santos, Hiroko H. Dodge, Steven D. Edland, Charlotte E. Teunissen, Ganesh M. Babulal, Hector M. González, Esther S. Oh, Donna M. Wilcock, Debora Melo van Lent, Michael Weinborn, Michelle M. Mielke, Carrie Ciro, Andre Strydom, James Hendrix, Catherine M. Roe, Roos J. Jutten, Graciela Muniz Terrera, Claudio Babiloni, Nicole Schupf, Melissa E. Murray, Benedict C. Albensi, Heather M. Snyder, Gaël Chételat, Gene L. Bowman, Elizabeth Head, Peggye Dilworth-Anderson, Anna J. Esbensen, Simone Dreux, Eider M. Arenaza-Urquijo, Adam M. Brickman, Sid E. O'Bryant, Mario A. Parra, Sietske A.M. Sikkes, Ann D. Cohen, Henrik Zetterberg, Martha Clare Morris, Leigh A. Johnson, Alex Bahar-Fuchs, Linda M.P. Wesselman, Lisbeth Evered, Keith N. Fargo, Joanne Bell, Arlene Astell, Juan Fortea, Michael Ewers, Nikolaos Scarmeas, Krista L. Lanctôt, Yaakov Stern, Hamid R. Sohrabi, Deborah Gustafson, Yi Tang, Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Massachusetts General Hospital [Boston], Harvard Medical School [Boston] (HMS), St. Boniface Hospital Albrechtsen Research Centre [Winnipeg], University of Manitoba [Winnipeg], Mayo Clinic [Rochester], University of Toronto, University of Reading (UOR), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], IRCCS-Hospital San Raffaele Pisana of Rome and Cassino, University of Melbourne, Syneos Health [Wilmington], Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Oregon Health & Science University [Portland], Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Columbia University [New York], Physiopathologie et imagerie des troubles neurologiques (PhIND), Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), University of Kansas [Kansas City], University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Harvard College [Cambridge], University of California [San Diego] (UC San Diego), University of California, University of Cincinnati (UC), Cincinnati Children's Hospital Medical Center, Klinikum der Universität [München], Medical & Scientific Relations, Alzheimer's Association [Chicago], Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona (UAB), Fundació Catalana de Síndrome de Down [Barcelona], Psychiatry and neurochemistry, SUNY Downstate Medical Center, State University of New York (SUNY), University of Kentucky, University of Victoria [Canada] (UVIC), University of North Texas Health Science Center [Fort Worth], VU University Medical Center [Amsterdam], University of Glasgow, Edith Cowan University [Joondalup], Rush University [Chicago], Mayo Clinic [Jacksonville], Johns Hopkins University School of Medicine [Baltimore], Department of Psychology [Edinburgh], Heriot-Watt University [Edinburgh] (HWU), Universidad Autonoma del Caribe [Barranquilla], University of Southern California (USC), Mailman School of Public Health Columbia University [New-York], Institute of Psychiatry, Psychology & Neuroscience, King's College London, King‘s College London, Xuan Wu Hospital [Beijing], Capital University of Medical Sciences [Beijing] (CUMS), University of Edinburgh, German Research Center for Neurodegenerative Diseases - Deutsches Zentrum für Neurodegenerative Erkrankungen (DZNE), Sahlgrenska University Hospital, University College of London [London] (UCL), University of Gothenburg (GU), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), University of California (UC), University of Kentucky (UK), and Duchange, Nathalie
Subjects: Gerontology, Ethnoracial, Aging, Biomedical Research, epidemiology [Alzheimer Disease], Alzheimer's related dementias, Ethnic group, Disease, Underserved, Neurodegenerative, cellular and molecular neuroscience, 0302 clinical medicine, White paper, Ethnicity, 030212 general & internal medicine, Alzheimer's Association, media_common, neurology (clinical), Diversity, Continental Population Groups, Translational, health policy, Alzheimer's disease, 3. Good health, psychiatry and mental health, epidemiology, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], geriatrics and gerontology, International Society to Advance Alzheimer's Research and Treatment, Alzheimer's Association, Population ageing, media_common.quotation_subject, Clinical Sciences, BF, Ethnic Groups, International Society to Advance Alzheimer's Research and Treatment, Article, Neglect, 03 medical and health sciences, Alzheimer Disease, Political science, medicine, diversity, ethnicity, ethnoracial, translational, underserved, developmental neuroscience, Acquired Cognitive Impairment, Dementia, Humans, [SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], ddc:610, Healthcare Disparities, Aged, ethnology [Alzheimer Disease], Racial Groups, Neurosciences, Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD), medicine.disease, Brain Disorders, Geriatrics, 030217 neurology & neurosurgery, Biomarkers, Diversity (politics)
Abstract: Altres ajuts: Fondo Europeo de Desarrollo Regional (FEDER), Unión Europea, "Una manera de hacer Europa", La "Marató TV3" grant (20141210 to J.F.) Alzheimer's disease and related dementias (ADRDs) are a global crisis facing the aging population and society as a whole. With the numbers of people with ADRDs predicted to rise dramatically across the world, the scientific community can no longer neglect the need for research focusing on ADRDs among underrepresented ethnoracial diverse groups. The Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART; alz.org/ISTAART) comprises a number of professional interest areas (PIAs), each focusing on a major scientific area associated with ADRDs. We leverage the expertise of the existing international cadre of ISTAART scientists and experts to synthesize a cross-PIA white paper that provides both a concise "state-of-the-science" report of ethnoracial factors across PIA foci and updated recommendations to address immediate needs to advance ADRD science across ethnoracial populations.
Published: 2019

25. The Mouse Microbiome Is Required for Sex-Specific Diurnal Rhythms of Gene Expression and Metabolism

Author: Aline Charpagne, Francis Foata, Jake Yeung, Benjamin D. Weger, Felix Naef, Bertrand Betrisey, Eva Martin, Frédéric Gachon, Aurélie Balvay, Sonia Jimenez, Cédric Gobet, Bernard Berger, Chieh Jason Chou, Anne Foussier, Brigitte Boizet-Bonhoure, Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Department of Diabetes and Circadian Rhythms, Nestlé Institute of Health Sciences, 1015 Lausanne, Switzerland., Ecole Polytechnique Fédérale de Lausanne (EPFL), Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland., Department of Diabetes and Circadian Rhythms, Nestlé Institute of Health Sciences, 1015 Lausanne, Switzerland, Cellular Metabolism, Department of Cell Biology, Nestlé Institute of Health Sciences, Nestlé Research, 1015 Lausanne, Switzerland., Nestle Res Ctr, Nestec Ltd, Host-Microbe Interaction, Department of Gastro-Intestinal Health, MICrobiologie de l'ALImentation au Service de la Santé (MICALIS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Genomics, Department of Multi-Omics, Nestlé Institute of Health Sciences, Nestlé Research, 1015 Lausanne, Switzerland, Institut de génétique humaine (IGH), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Nestlé Research Center, Nestle Reasearch Center, Institute of Bioengineering, School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland, Swiss National Science Foundation [310030_173079], Natural Sciences and Engineering Research Council of Canada Postgraduate Studies Doctoral Scholarship, European Project: 260988,EC:FP7:ERC,ERC-2010-StG_20091118,CIRCATRANS(2011), Nestlé Research Center | Centre de recherche Nestlé [Lausanne], Nestlé S.A., and School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne, 1015 Lausanne, Switzerland
Subjects: 0301 basic medicine, Male, Physiology, [SDV]Life Sciences [q-bio], Circadian clock, nuclear receptors, Gene Expression, White adipose tissue, Transcriptome, Mice, 0302 clinical medicine, circadian clock, reproductive function, Sex Characteristics, sexual maturation, Growth hormone secretion, symbiosis, Cell biology, Circadian Rhythm, Intestines, germ-free, ghrelin, Female, diet-induced obesity, Adipose Tissue, White, Feminization (biology), Bcl6, Biology, liver, Article, 03 medical and health sciences, Circadian Clocks, Metabolome, microbiota, Animals, Humans, Microbiome, Molecular Biology, [SDV.GEN]Life Sciences [q-bio]/Genetics, gut microbiota, aryl-hydrocarbon receptor, growth-hormone-secretion, Cell Biology, signaling pathways, Gastrointestinal Microbiome, Mice, Inbred C57BL, Sexual dimorphism, 030104 developmental biology, cyp1a1 expression, sexual dimorphism, growth hormone, 030217 neurology & neurosurgery
Abstract: Summary The circadian clock and associated feeding rhythms have a profound impact on metabolism and the gut microbiome. To what extent microbiota reciprocally affect daily rhythms of physiology in the host remains elusive. Here, we analyzed transcriptome and metabolome profiles of male and female germ-free mice. While mRNA expression of circadian clock genes revealed subtle changes in liver, intestine, and white adipose tissue, germ-free mice showed considerably altered expression of genes associated with rhythmic physiology. Strikingly, the absence of the microbiome attenuated liver sexual dimorphism and sex-specific rhythmicity. The resulting feminization of male and masculinization of female germ-free animals is likely caused by altered sexual development and growth hormone secretion, associated with differential activation of xenobiotic receptors. This defines a novel mechanism by which the microbiome regulates host metabolism., Graphical Abstract, Highlights • The microbiome is required for sexual dimorphism in gene expression and metabolism • Most already-described changes in GF mice are hallmarks of a feminized metabolism • Altered sexual maturation and GH secretion cause the damping of sexual dimorphism • Microbiota-derived metabolites and ghrelin likely drive these alterations, Physiology is dynamic over the day and different between sexes. Weger et al. show that the microbiome play a key role in sustaining these sex differences in gene expression and metabolism by ensuring proper sexual maturation and growth hormone secretion. Microbiota-derived metabolites and ghrelin likely drive these sexually dimorphic dynamics.
Published: 2019

26. Identification of Pre-frailty Sub-Phenotypes in Elderly Using Metabolomics

Author: Pujos-Guillot, Estelle, Pétéra, Mélanie, Jacquemin, Jérémie, Centeno, Delphine, Lyan, Bernard, Montoliu, Ivan, Madej, Dawid, Pietruszka, Barbara, Fabbri, Cristina, Santoro, Aurelia, Brzozowska, Anna, Franceschi, Claudio, Comte, Blandine, Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Plateforme d'Exploration du Métabolisme, Institut National de la Recherche Agronomique (INRA), Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Human Nutrition, Szkoła Główna Gospodarstwa Wiejskiego w Warszawie, Warsaw University of Life Sciences (SGGW), Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Centro Interdipartimentale « L. Galvani» (CIG), Institute of Neurological Sciences of Bologna IRCCS, European Union's Seventh Framework Program 266486, MetaboHUB French infrastructure ANR-INBS-0010, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), European Project: 266486,EC:FP7:KBBE,FP7-KBBE-2010-4,NU-AGE(2011), Plateforme Exploration du Métabolisme (PFEM), Institut National de la Recherche Agronomique (INRA)-Université Blaise Pascal - Clermont-Ferrand 2 (UBP)-MetaboHUB-Clermont, MetaboHUB-MetaboHUB, Alma Mater Studiorum Università di Bologna [Bologna] (UNIBO), Pujos-Guillot, Estelle, Pétéra, Mélanie, Jacquemin, Jérémie, Centeno, Delphine, Lyan, Bernard, Montoliu, Ivan, Madej, Dawid, Pietruszka, Barbara, Fabbri, Cristina, Santoro, Aurelia, Brzozowska, Anna, Franceschi, Claudio, and Comte, Blandine
Subjects: untargeted metabolomics, pre-frailty, sub-phenotypes, Physiology, gender differences, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, gender difference, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], biomarker, biomarkers, sub-phenotype, elderly, Original Research
Abstract: Aging is a dynamic process depending on intrinsic and extrinsic factors and its evolution is a continuum of transitions, involving multifaceted processes at multiple levels. It is recognized that frailty and sarcopenia are shared by the major age-related diseases thus contributing to elderly morbidity and mortality. Pre-frailty is still not well understood but it has been associated with global imbalance in several physiological systems, including inflammation, and in nutrition. Due to the complex phenotypes and underlying pathophysiology, the need for robust and multidimensional biomarkers is essential to move toward more personalized care. The objective of the present study was to better characterize the complexity of pre-frailty phenotype using untargeted metabolomics, in order to identify specific biomarkers, and study their stability over time. The approach was based on the NU-AGE project (clinicaltrials.gov , NCT01754012) that regrouped 1,250 free-living elderly people (65-79 y.o., men and women), free of major diseases, recruited within five European centers. Half of the volunteers were randomly assigned to an intervention group (1-year Mediterranean type diet). Presence of frailty was assessed by the criteria proposed by Fried et al. (2001). In this study, a sub-cohort consisting in 212 subjects (pre-frail and non-frail) from the Italian and Polish centers were selected for untargeted serum metabolomics at T0 (baseline) and T1 (follow-up). Univariate statistical analyses were performed to identify discriminant metabolites regarding pre-frailty status. Predictive models were then built using linear logistic regression and ROC curve analyses were used to evaluate multivariate models. Metabolomics enabled to discriminate sub-phenotypes of pre-frailty both at the gender level and depending on the pre-frailty progression and reversibility. The best resulting models included four different metabolites for each gender. They showed very good prediction capacity with AUCs of 0.93 (95% CI = 0.87-1) and 0.94 (95% CI = 0.87-1) for men and women, respectively. Additionally, early and/or predictive markers of pre-frailty were identified for both genders and the gender specific models showed also good performance (three metabolites; AUC = 0.82; 95% CI = 0.72-0.93) for men and very good for women (three metabolites; AUC = 0.92; 95% CI = 0.86-0.99). These results open the door, through multivariate strategies, to a possibility of monitoring the disease progression over time at a very early stage.
Published: 2019

27. Validation of EN ISO method 15216 - Part 1 – Quantification of hepatitis A virus and norovirus in food matrices

Author: Joanna Ollivier, Gwenola Hardouin, P.H. in’t Veld, Sophie Butot, Alexandre Leclercq, Bertrand Lombard, S.A. Rutjes, James A. Lowther, Albert Bosch, D. Mäde, Centre for Environment, Fisheries and Aquaculture Science [Weymouth] (CEFAS), Universitat de Barcelona (UB), Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Laboratoire de Microbiologie, Environnement, Microbiologie et Phycotoxines (EMP), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Lower Saxony State Office for Consumer Protection and Food Safety, National Institute for Public Health and the Environment [Bilthoven] (RIVM), Association Française de Normalisation (AFNOR), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Netherlands Food and Consumer Product Safety Authority (NVWA), Centre National de Référence Listeria - National Reference Center Listeria (CNRL), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biologie des Infections - Biology of Infection, Centre collaborateur de l'OMS Listeria / WHO Collaborating Centre Listeria (CC-OMS / WHO-CC), Institut Pasteur [Paris] (IP)-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), The validation of International Standard EN ISO 15216-1 was carried out under the framework of European Mandate No. M381 of DG SANTE and DG GROW (European Commission)., DIAKITE, andrée, Laboratoire de Microbiologie, IFREMER, Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut Pasteur [Paris]-Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO)
Subjects: 0301 basic medicine, Bivalve molluscan shellfish, Standardization, [SDV]Life Sciences [q-bio], MESH: Bivalvia, medicine.disease_cause, Limit of Detection, MESH: Reverse Transcriptase Polymerase Chain Reaction, Validation, Vegetables, MESH: Animals, Risk management, MESH: Shellfish, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Reverse Transcriptase Polymerase Chain Reaction, General Medicine, Bottled water, Hepatitis a virus, 3. Good health, Surfaces, MESH: Reproducibility of Results, [SDV] Life Sciences [q-bio], [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, MESH: Fruit, MESH: Norovirus, 030106 microbiology, MESH: Limit of Detection, Biology, Microbiology, 03 medical and health sciences, Environmental health, MESH: Hepatitis A virus, Soft fruit, medicine, MESH: European Union, Food microbiology, Animals, Humans, European Union, MESH: Food Microbiology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Shellfish, MESH: Humans, business.industry, International standard, Norovirus, Reproducibility of Results, Virology, MESH: Vegetables, Bivalvia, Real-time RT-PCR, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Fruit, Food Microbiology, Hepatitis A virus, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Food Science
Abstract: International audience; Hepatitis A virus (HAV) and norovirus are important agents of food-borne human viral illness, with common vehicles including bivalve molluscan shellfish, soft fruit and various vegetables. Outbreaks of viral illness due to contamination of the surfaces of foods, or food preparation surfaces by for example infected food handlers are also common. Virus analysis of food matrices can contribute towards risk management for these hazards and a two-part technical specification for determination of Hepatitis A virus and norovirus in food matrices (ISO/TS 15216:2013) was published jointly by the European Committee for Standardisation and the International Organization for Standardization in 2013.As part of the European Mandate No. M381 to validate 15 standards in the field of food microbiology, an international validation study involving 18 laboratories from 11 countries in Europe was conducted between 2012 and 2014. This study aimed to generate method characteristics including limit of detection, limit of quantification, repeatability and reproducibility for ISO 15216 – Part 1, the method for quantification, in seven food matrices.The organization and results of this study, including observations that led to improvements in the standard method are presented here. After its conclusion, the method characteristics generated were added to the revised international standard, ISO 15216-1:2017, published in March 2017.
Published: 2019

28. Structure and Function of Bovine Whey Derived Oligosaccharides Showing Synbiotic Epithelial Barrier Protective Properties

Author: Christine Cherbut, Sean Austin, Mireille Golliard, Nadine Porta, Peter I. Duncan, Juhani Saarinen, Olli Aitio, Jari Helin, Muriel Fiaux, Rafael Berrocal, Annamari Heiskanen, Norbert Sprenger, Ritva Niemelä, Denis Moënnoz, Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Glykos Finland Ltd, Nestlé Product Technology Center, Nestlé Institute of Food Safety and Analytical Sciences, and Societe des Produits Nestle S.A. Societe des Produits Nestle S.A., Switzerland
Subjects: 0301 basic medicine, Bifidobacterium longum, medicine.medical_treatment, Oligosaccharides, Synbiotics, Gut flora, medicine.disease_cause, law.invention, Enterotoxins, Probiotic, law, Intestinal Mucosa, lactobacillus probiotic, 2. Zero hunger, chemistry.chemical_classification, Nutrition and Dietetics, biology, Oligosaccharide, 3. Good health, host-microbiota interaction, Biochemistry, lcsh:Nutrition. Foods and food supply, Bacterial Toxins, 030106 microbiology, Clostridium difficile toxin A, lcsh:TX341-641, host–microbiota interaction, Protective Agents, Article, 03 medical and health sciences, Lactobacillus rhamnosus, Cell Line, Tumor, Whey, medicine, Animals, Humans, Escherichia coli, epithelial barrier function, Probiotics, Prebiotic, Galactose, biology.organism_classification, Gastrointestinal Microbiome, Lactobacillus, Prebiotics, 030104 developmental biology, chemistry, Cattle, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Food Science
Abstract: Commensal gut microbiota and probiotics have numerous effects on the host&rsquo, s metabolic and protective systems, which occur primarily through the intestinal epithelial cell interface. Prebiotics, like galacto-oligosaccharides (GOS) are widely used to modulate their function and abundance. However, important structure&ndash, function relations may exist, requiring a detailed structural characterization. Here, we detailed the structural characterization of bovine whey derived oligosaccharide preparations enriched with GOS or not, dubbed GOS-enriched milk oligosaccharides (GMOS) or MOS, respectively. We explore GMOS&rsquo, s and MOS&rsquo, s potential to improve intestinal epithelial barrier function, assessed in a model based on barrier disruptive effects of the Clostridioides difficile toxin A. GMOS and MOS contain mainly GOS species composed of &beta, 1-6- and &beta, 1-3-linked galactoses, and 3&prime, and 6&prime, sialyllactose. Both GMOS and MOS, combined with lactobacilli, like Lactobacillus rhamnosus (LPR, NCC4007), gave synergistic epithelial barrier protection, while no such effect was observed with Bifidobacterium longum (BL NCC3001), Escherichia coli (Nissle) or fructo-oligosaccharides. Mechanistically, for barrier protection with MOS, (i) viable LPR was required, (ii) acidification of growth medium was not enough, (iii) LPR did not directly neutralize toxin A, and (iv) physical proximity of LPR with the intestinal epithelial cells was necessary. This is the first study, highlighting the importance of structure&ndash, function specificity and the necessity of the simultaneous presence of prebiotic, probiotic and host cell interactions required for a biological effect.
Published: 2020

29. Early Effect of Supplemented Infant Formulae on Intestinal Biomarkers and Microbiota: A Randomized Clinical Trial

Author: Nadja Haiden, Nanda de Groot, Philippe Steenhout, Mireille Castanet, Norbert Sprenger, Christos Costalos, Harald Brüssow, Sophie Pecquet, Dominik Grathwohl, Jean-Michel Hascoet, Jalil Benyacoub, Jean-Charles Picaud, Bernard Berger, Centre d'Investigation Clinique [CHU Rouen] (CIC Rouen), Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Alexandra Regional General Hospital [Athens, Greece], Medizinische Universität Wien = Medical University of Vienna, Maternité Régionale Adolphe Pinard [Nancy], Développement, Adaptation et Handicap. Régulations cardio-respiratoires et de la motricité (DevAH), Université de Lorraine (UL), Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], SBU Nutrition [Vevey, Switzerland] (Nestlé ), Nestlé Health Science [Epalinges, Switzerland], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Service de Néonatologie [Lyon] (Hôpital de la Croix-Rousse [CHU - HCL]), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Societe des Produits Nestle S.A. Switzerland, HASCOET, JEAN-MICHEL, Hôpital Charles Nicolle [Rouen]-CHU Rouen, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL)
Subjects: 0301 basic medicine, Oligosaccharides, Physiology, Gut flora, law.invention, Feces, chemistry.chemical_compound, fluids and secretions, 0302 clinical medicine, Randomized controlled trial, law, Bifidobacterium, 2. Zero hunger, Nutrition and Dietetics, biology, Lactoferrin, Elastase, Neopterin, Infant Formula, 3. Good health, Breast Feeding, Milk, lcsh:Nutrition. Foods and food supply, lcsh:TX341-641, digestive system, Article, infant microbiota, 03 medical and health sciences, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, Bifidobacterium animalis, Double-Blind Method, 030225 pediatrics, Animals, Humans, early gut maturation, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, Infant, biology.organism_classification, Gastrointestinal Microbiome, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, 030104 developmental biology, probiotics, chemistry, Dietary Supplements, biology.protein, Calprotectin, prebiotics, Leukocyte L1 Antigen Complex, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Biomarkers, Food Science
Abstract: Background: Post-natal gut maturation in infants interrelates maturation of the morphology, digestive, and immunological functions and gut microbiota development. Here, we explored both microbiota development and markers of gut barrier and maturation in healthy term infants during their early life to assess the interconnection of gut functions during different infant formulae regimes. Methods: A total of 203 infants were enrolled in this randomized double-blind controlled trial including a breastfed reference group. Infants were fed starter formulae for the first four weeks of life, supplemented with different combination of nutrients (lactoferrin, probiotics (Bifidobacterium animal subsp. Lactis) and prebiotics (Bovine Milk-derived Oligosaccharides&mdash, BMOS)) and subsequently fed the control formula up to eight weeks of life. Stool microbiota profiles and biomarkers of early gut maturation, calprotectin (primary outcome), elastase, &alpha, 1 antitrypsin (AAT) and neopterin were measured in feces at one, two, four, and eight weeks. Results: Infants fed formula containing BMOS had lower mean calprotectin levels over the first two to four weeks compared to the other formula groups. Elastase and AAT levels were closer to levels observed in breastfed infants. No differences were observed for neopterin. Global differences between the bacterial communities of all groups were assessed by constrained multivariate analysis with hypothesis testing. The canonical correspondence analysis (CCA) at genus level showed overlap between microbiota profiles at one and four weeks of age in the BMOS supplemented formula group with the breastfed reference, dominated by bifidobacteria. Microbiota profiles of all groups at four weeks were significantly associated with the calprotectin levels at 4 (CCA, p = 0.018) and eight weeks of age (CCA, p = 0.026). Conclusion: A meaningful correlation was observed between changes in microbiota composition and gut maturation marker calprotectin. The supplementation with BMOS seems to favor gut maturation closer to that of breastfed infants.
Published: 2020

30. Bioaccessibility of Biofortified Sweet Potato Carotenoids in Baby Food: Impact of Manufacturing Process

Author: Claudie Dhuique-Mayer, Adrien Servent, Charlotte Messan, Nawel Achir, Manuel Dornier, Yery Mendoza, Démarche intégrée pour l'obtention d'aliments de qualité (UMR Qualisud), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-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)-Université de La Réunion (UR)-Université de Montpellier (UM)-Avignon Université (AU)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), Département Performances des systèmes de production et de transformation tropicaux (Cirad-PERSYST), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), and Nestlé Institute of Health Sciences SA [Lausanne, Switzerland]
Subjects: 0301 basic medicine, Vitamin, industrial processes, food.ingredient, in vitro digestion, Endocrinology, Diabetes and Metabolism, Pasteurization, lcsh:TX341-641, Biology, law.invention, Baby food, 03 medical and health sciences, chemistry.chemical_compound, 0404 agricultural biotechnology, food, law, Yolk, medicine, Food science, Carotenoid, Nutrition, Original Research, 2. Zero hunger, chemistry.chemical_classification, orange sweet potato, 030109 nutrition & dietetics, Nutrition and Dietetics, Retinol, food and beverages, 04 agricultural and veterinary sciences, Sterilization (microbiology), medicine.disease, 040401 food science, Vitamin A deficiency, chemistry, baby food, pro-vitamin A, lcsh:Nutrition. Foods and food supply, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Food Science
Abstract: International audience; Orange-fleshed sweet potato (OFSP), a biofortified crop rich in β-carotene, can be used as a component of baby food recipes in order to tackle vitamin A deficiency in children
Published: 2018

31. Microbial-derived products as potential new antimicrobials

Author: Bruce S. Seal, Djamel Drider, Brian B. Oakley, Harald Brüssow, David Bikard, Joseph O. Rich, Stefan Miller, Estelle Devillard, Jason Kwan, Gérard Bertin, Stuart Reeves, Steven M. Swift, Margot Raicek, Cyril G. Gay, Oregon State University (OSU), Institut Charles Viollette (ICV) - ULR 7394 (ICV), Université d'Artois (UA)-Université du Littoral Côte d'Opale (ULCO)-Institut Supérieur d'Agriculture-Université de Lille-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Western University of Health Sciences, Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Biologie de Synthèse - Synthetic biology, Institut Pasteur [Paris], National Center for Agricultural Utilization Research (NCAUR), United States Department of Agriculture (USDA), Lisando GmbH, Adisseo France SAS, University of Wisconsin-Madison, Erawan consulting, Embria Health Sciences, Animal Biosciences and Biotechnology, United States Department of Agriculture, Organisation Mondiale de la Santé Animale / World Animal Health Information System (OIE-WAHIS), USDA-ARS : Agricultural Research Service, Institut Pasteur [Paris] (IP), and Organisation Mondiale de la Santé Animale / World Organisation Animal Health [Paris] (OIE)
Subjects: 0301 basic medicine, MESH: CRISPR-Cas Systems, [SDV]Life Sciences [q-bio], Antibiotics, Review, Antimicrobial Growth Promoters (AGPs), Commercialization, Animal Diseases, MESH: Bacteriocins, Anti-Infective Agents, Bacteriocins, Drug Discovery, Fecal Microbiome Transplants, Bacteriophages, Direct-fed Microbials (DFMs), MESH: Animals, Animal Husbandry, 2. Zero hunger, lcsh:Veterinary medicine, Animal health, MESH: Animal Husbandry, Authorization, Antimicrobial, 3. Good health, MESH: Livestock, France, Livestock, medicine.drug_class, MESH: Anti-Infective Agents, 030106 microbiology, Antimicrobial peptides, Probiotic Development, Biology, 03 medical and health sciences, Antibiotic resistance, MESH: Drug Discovery, medicine, Animals, MESH: Bacteriophages, Microbiome, General Veterinary, business.industry, MESH: Animal Diseases, Biotechnology, MESH: France, 030104 developmental biology, 13. Climate action, lcsh:SF600-1100, CRISPR-Cas Systems, Food-animal Production, business
Abstract: International audience; Due to the continuing global concerns involving antibiotic resistance, there is a need for scientific forums to assess advancements in the development of antimicrobials and their alternatives that might reduce development and spread of antibiotic resistance among bacterial pathogens. The objectives of the 2nd International Symposium on Alternatives to Antibiotics were to highlight promising research results and novel technologies that can provide alternatives to antibiotics for use in animal health and production, assess challenges associated with their authorization and commercialization for use, and provide actionable strategies to support their development. The session on microbial-derived products was directed at presenting novel technologies that included exploiting CRISPR-Cas nucleases to produce sequence-specific antimicrobials, probiotics development via fecal microbiome transplants among monogastric production animals such as chickens and mining microbial sources such as bacteria or yeast to identify new antimicrobial compounds. Other research has included continuing development of antimicrobial peptides such as newly discovered bacteriocins as alternatives to antibiotics, use of bacteriophages accompanied by development of unique lytic proteins with specific cell-wall binding domains and novel approaches such as microbial-ecology guided discovery of anti-biofilm compounds discovered in marine environments. The symposium was held at the Headquarters of the World Organisation for Animal Health (OIE) in Paris, France during 12–15 December 2016.
Published: 2018

32. Sulfoximines as potent RORγ inverse agonists

Author: Etienne Thoreau, Craig S. Harris, David Froude, Franck Bihl, Gilles Ouvry, Delphine Spiesse, Patricia Rossio, Christophe Feret, Emmanuel Vial, Laurent F. Hennequin, Jonathan Pascau, Coralie Pascau, Romain Pierre, Claire Defoin-Platel, Nathalie Taquet, Catherine Hervouet, Veronique Parnet, Olivier Christin, Guillaume Lafitte, Sophie Deret, Catherine Raffin, Claire Bouix-Peter, Anne-Pascale Luzy, Feriel Hacini-Rachinel, Branislav Musicki, Danielle Orfila, Rodolphe Vatinel, Laboratoire de synthèse organique (DCSO), École polytechnique (X)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Nestle Skin Health GALDERMA R&D, Religions et croyances (LARHRA REC ), LAboratoire de Recherche Historique Rhône-Alpes - UMR5190 (LARHRA), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire d'Immunologie et Immunopathologie [CHU Poitiers] (CNRS URA 1172), Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Centre National de la Recherche Scientifique (CNRS), Mucosal Immunity, Vaccination, and Biometrics -- Immunité des muqueuses, vaccinations et biothérapies, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Transporteurs et Imagerie, Radiothérapie en Oncologie et Mécanismes biologiques des Altérations du Tissu Osseux (TIRO-MATOs - UMR E4320), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-UMR E4320 (TIRO-MATOs), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-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)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA), Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], GALDERMA R&D, Galderma Recherche et Développement [Biot, France] (Galderma R&D), Virologie humaine, École normale supérieure de Lyon (ENS de Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), AstraZeneca, Cancer and Infection Research, Université Nice Sophia Antipolis (... - 2019) (UNS), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), UMR E4320 (TIRO-MATOs), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-Service Hospitalier Frédéric Joliot (SHFJ), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, and École normale supérieure - Lyon (ENS Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Drug Inverse Agonism, [SDV]Life Sciences [q-bio], Clinical Biochemistry, Pharmaceutical Science, Context (language use), Pharmacology, Ligands, 010402 general chemistry, 01 natural sciences, Biochemistry, Structure-Activity Relationship, chemistry.chemical_compound, In vivo, Drug Discovery, Animals, Humans, Inverse agonist, Potency, [CHIM]Chemical Sciences, Hydroxymethyl, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Mice, Inbred BALB C, Sulfonamides, Molecular Structure, 010405 organic chemistry, Organic Chemistry, Stereoisomerism, Biological activity, Nuclear Receptor Subfamily 1, Group F, Member 3, 0104 chemical sciences, 3. Good health, chemistry, Nuclear receptor, Sulfoxides, Lipophilicity, Molecular Medicine, Female, Imines
Abstract: Progress in the identification of suitable RORγ inverse agonists as clinical candidates has been hampered by the high lipophilicity that seems required for high potency on this nuclear receptor. In this context, we decided to focus on the replacement of the hydroxymethyl group found on known modulators to determine if more polarity could be tolerated in this position. SAR of the replacement of this moiety is presented in this article leading to the identification of sulfoximine derivatives as potent modulators with pharmacological activity in the in vivo mouse Imiquimod psoriasis model.
Published: 2018

33. Discovery and Characterization of CD12681, a Potent RORγ Inverse Agonist, Preclinical Candidate for the Topical Treatment of Psoriasis

Author: Coralie Pascau, Nicolas Atrux-Tallau, Laurent F. Hennequin, Christophe Feret, Gilles Ouvry, Feriel Hacini-Rachinel, Craig S. Harris, Claire Defoin-Platel, Nathalie Taquet, Sophie Deret, Mathieu Forissier, Hélène Huguet, Etienne Thoreau, Benjamin Ozello, Olivier Christin, Emmanuel Vial, Guillaume Lafitte, Danielle Orfila, Isabelle Carlavan, Franck Bihl, David Froude, Jean-François Fournier, Denis Duvert, Anne-Pascale Luzy, Delphine Spiesse, Patricia Rossio, Marie-Josée Cuadrado, Jonathan Pascau, Catherine Raffin, Aline Bondu, Claire Bouix-Peter, Catherine Hervouet, Guillaume Peluchon, Veronique Parnet, David Piwnica, Branislav Musicki, Rodolphe Vatinel, Romain Pierre, Laboratoire de synthèse organique (DCSO), École polytechnique (X)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de pharmacologie moléculaire et cellulaire (IPMC), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS), Nestle Skin Health GALDERMA R&D, Religions et croyances (LARHRA REC ), LAboratoire de Recherche Historique Rhône-Alpes - UMR5190 (LARHRA), École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-École normale supérieure de Lyon (ENS de Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Laboratoire d'Immunologie et Immunopathologie [CHU Poitiers] (CNRS URA 1172), Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Centre National de la Recherche Scientifique (CNRS), Mucosal Immunity, Vaccination, and Biometrics -- Immunité des muqueuses, vaccinations et biothérapies, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Transporteurs et Imagerie, Radiothérapie en Oncologie et Mécanismes biologiques des Altérations du Tissu Osseux (TIRO-MATOs - UMR E4320), Service Hospitalier Frédéric Joliot (SHFJ), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-UMR E4320 (TIRO-MATOs), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-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)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA), Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Institut de Recherches SERVIER (IRS), GALDERMA R&D, Galderma Recherche et Développement [Biot, France] (Galderma R&D), Virologie humaine, École normale supérieure de Lyon (ENS de Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Nice Sophia Antipolis (... - 2019) (UNS), École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-École normale supérieure - Lyon (ENS Lyon)-Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), UMR E4320 (TIRO-MATOs), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Côte d'Azur (UCA)-Service Hospitalier Frédéric Joliot (SHFJ), Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, and École normale supérieure - Lyon (ENS Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Keratinocytes, Administration, Topical, [SDV]Life Sciences [q-bio], Retinoic acid, Drug Evaluation, Preclinical, Pharmacology, 01 natural sciences, Biochemistry, Interleukin-23, chemistry.chemical_compound, Mice, Drug Discovery, heterocyclic compounds, General Pharmacology, Toxicology and Pharmaceutics, ComputingMilieux_MISCELLANEOUS, Orphan receptor, Mice, Inbred BALB C, Sulfonamides, Interleukin-17, Nuclear Receptor Subfamily 1, Group F, Member 3, 3. Good health, Molecular Medicine, medicine.symptom, Drug Inverse Agonism, Inflammation, Topical treatment, Skin Diseases, 03 medical and health sciences, Inhibitory Concentration 50, Structure-Activity Relationship, In vivo, Psoriasis, medicine, Inverse agonist, Animals, Humans, [CHIM]Chemical Sciences, 010405 organic chemistry, business.industry, Organic Chemistry, medicine.disease, 0104 chemical sciences, Disease Models, Animal, 030104 developmental biology, chemistry, Mouse skin, Th17 Cells, business
Abstract: With possible implications in multiple autoimmune diseases, the retinoic acid receptor-related orphan receptor RORγ has become a sought-after target in the pharmaceutical industry. Herein are described the efforts to identify a potent RORγ inverse agonist compatible with topical application for the treatment of skin diseases. These efforts culminated in the discovery of N-(2,4-dimethylphenyl)-N-isobutyl-2-oxo-1-[(tetrahydro-2H-pyran-4-yl)methyl]-2,3-dihydro-1H-benzo[d]imidazole-5-sulfonamide (CD12681), a potent inverse agonist with in vivo activity in an IL-23-induced mouse skin inflammation model.
Published: 2018

34. Structure and Distribution of Centromeric Retrotransposons at Diploid and Allotetraploid Coffea Centromeric and Pericentromeric Regions

Author: Renata de Castro Nunes, Simon Orozco-Arias, Dominique Crouzillat, Lukas A. Mueller, Suzy R. Strickler, Patrick Descombes, Coralie Fournier, Deborah Moine, Alexandre de Kochko, Priscila M. Yuyama, André L. L. Vanzela, Romain Guyot, State University of Londrina = Universidade Estadual de Londrina, Universidad Autónoma de Manizales (UAM), Cornell University [New York], Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Diversité, adaptation, développement des plantes (UMR DIADE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), UMR - Interactions Plantes Microorganismes Environnement (UMR IPME), Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), and Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Université de Montpellier (UM)-Institut de Recherche pour le Développement (IRD [France-Sud])
Subjects: 0106 biological sciences, 0301 basic medicine, Heterochromatin, Canephora, coffee, Retrotransposon, Plant Science, lcsh:Plant culture, Coffea canephora, 01 natural sciences, Genome, Coffee, [SDV.GEN.GPL]Life Sciences [q-bio]/Genetics/Plants genetics, 03 medical and health sciences, pseudochromosomes, FISH, Gypsy, Chromosome regions, Centromere, lcsh:SB1-1110, Original Research, Centromeres, biology, CRM lineages, fungi, proximal chromosome regions, food and beverages, centromeres, biology.organism_classification, Proximal chromosome regions, 030104 developmental biology, Evolutionary biology, Ploidy, 010606 plant biology & botany, Pseudochromosomes
Abstract: International audience; Centromeric regions of plants are generally composed of large array of satellites from a specific lineage of Gypsy LTR-retrotransposons, called Centromeric Retrotransposons. Repeated sequences interact with a specific H3 histone, playing a crucial function on kinetochore formation. To study the structure and composition of centromeric regions in the genus Coffea, we annotated and classified Centromeric Retrotransposons sequences from the allotetraploid C. arabica genome and its two diploid ancestors: Coffea canephora and C. eugenioides. Ten distinct CRC (Centromeric Retrotransposons in Coffea) families were found. The sequence mapping and FISH experiments of CRC Reverse Transcriptase domains in C. canephora, C. eugenioides, and C. arabica clearly indicate a strong and specific targeting mainly onto proximal chromosome regions, which can be associated also with heterochromatin. PacBio genome sequence analyses of putative centromeric regions on C. arabica and C. canephora chromosomes showed an exceptional density of one family of CRC elements, and the complete absence of satellite arrays, contrasting with usual structure of plant centromeres. Altogether, our data suggest a specific centromere organization in Coffea, contrasting with other plant genomes.
Published: 2018

35. Lipidomics reveals diurnal lipid oscillations in human skeletal muscle persisting in cellular myotubes cultured in vitro

Author: Ursula Loizides-Mangold, Leonidas G. Karagounis, Bart Vandereycken, Howard Riezman, Benjamin D. Weger, Laurent Perrin, Etienne Lefai, Marc Moniatte, Stéphanie Chanon, Frédéric Gachon, Iain Templeman, Charna Dibner, Jean-Philippe Walhin, Maud Robert, Jonathan Paz Montoya, Christine Durand, Jonathan D. Johnston, James A. Betts, Geneva University Hospital (HUG), Section de mathématiques [Genève], Université de Genève (UNIGE), University of Bath [Bath], Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Ecole Polytechnique Fédérale de Lausanne (EPFL), Plymouth University, University of Surrey (UNIS), Sinergia Swiss National Science Foundation [CRSII3-154405], Swiss National Science Foundation [31003A-166700], [310030B-166686], National Centre of Competence in Research Chemical Biology, Fondation Romande pour la Recherche sur le Diabete, Fondation Ernst et Lucie Schmidheiny, Societe Academique de Geneve, United Kingdom Biotechnology and Biological Sciences Research Council [BB/I008470/1], Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL)
Subjects: 0301 basic medicine, Muscle tissue, [SDV]Life Sciences [q-bio], Circadian clock, Muscle Fibers, Skeletal, Biology, In Vitro Techniques, Cell Physiological Phenomena, 03 medical and health sciences, Lipidomics, circadian clock, lipid metabolism, medicine, Homeostasis, Humans, human primary myotubes, ddc:510, Muscle, Skeletal, ddc:612, Cells, Cultured, ComputingMilieux_MISCELLANEOUS, ddc:616, Multidisciplinary, Myogenesis, Skeletal muscle, Lipid metabolism, human skeletal muscle, Sphingolipid, Lipids, Healthy Volunteers, Circadian Rhythm, CLOCK, 030104 developmental biology, medicine.anatomical_structure, Biochemistry, PNAS Plus, ddc:540, lipidomics, lipids (amino acids, peptides, and proteins)
Abstract: International audience; Circadian clocks play an important role in lipid homeostasis, with impact on various metabolic diseases. Due to the central role of skeletal muscle in whole-body metabolism, we aimed at studying muscle lipid profiles in a temporal manner. Moreover, it has not been shown whether lipid oscillations in peripheral tissues are driven by diurnal cycles of rest-activity and food intake or are able to persist in vitro in a cell-autonomous manner. To address this, we investigated lipid profiles over 24 h in human skeletal muscle in vivo and in primary human myotubes cultured in vitro. Glycerolipids, glycerophos-pholipids, and sphingolipids exhibited diurnal oscillations, suggesting a widespread circadian impact on muscle lipid metabolism. Notably, peak levels of lipid accumulation were in phase coherence with core clock gene expression in vivo and in vitro. The percentage of oscillating lipid metabolites was comparable between muscle tissue and cultured myotubes, and temporal lipid profiles correlatedwith transcript profiles of genes implicated in their biosynthesis. Lipids enriched in the outer leaflet of the plasma membrane oscillated in a highly coordinated manner in vivo and in vitro. Lipid metabolite oscillations were strongly attenuated upon siRNA-mediated clock disruption in human primary myotubes. Taken together, our data suggest an essential role for endogenous cell-autonomous human skeletal muscle oscillators in regulating lipid metabolism independent of external synchronizers, such as physical activity or food intake.
Published: 2017

36. AMPK α1‐ LDH pathway regulates muscle stem cell self‐renewal by controlling metabolic homeostasis

Author: Kei Sakamoto, Marc Foretz, Pascual Sanz, Guillaume Vial, Dominique Desplanches, Laurent Bultot, Sabrina Ben Larbi, Linda Gsaier, Benoit Viollet, Bénédicte Chazaud, Anne Brunet, Marine Theret, Gaëtan Juban, Caterina Collodet, Rémi Mounier, Bethany E. Schaffer, Lin Yang, Michèle Weiss-Gayet, Zizhao Zang, Institut NeuroMyoGène (INMG), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Paris Descartes - Paris 5 (UPD5), Stanford University, Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Ecole Polytechnique Fédérale de Lausanne (EPFL), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Consejo Superior de Investigaciones Científicas [Spain] (CSIC), University of Florida [Gainesville] (UF), Hypoxie : Physiopathologie Respiratoire et Cardiovasculaire (HP2 ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Vial, Guillaume, European Commission, Sanz, Pascual, and Sanz, Pascual [0000-0002-2399-4103]
Subjects: 0301 basic medicine, [SDV.BA] Life Sciences [q-bio]/Animal biology, Cellular differentiation, [SDV]Life Sciences [q-bio], Cell, stem cell fate, AMP-Activated Protein Kinases, Biology, General Biochemistry, Genetics and Molecular Biology, Mice, 03 medical and health sciences, chemistry.chemical_compound, Skeletal muscle regeneration, Lactate dehydrogenase, Stem cell fate, skeletal muscle regeneration, medicine, Animals, Homeostasis, Glycolysis, Cell Self Renewal, Protein kinase A, Molecular Biology, Features, Mice, Knockout, L-Lactate Dehydrogenase, General Immunology and Microbiology, Muscles, Stem Cells, General Neuroscience, [SDV.BA]Life Sciences [q-bio]/Animal biology, AMPK, Cell Differentiation, Articles, Metabolism, Metabolic shift, glycolysis, 3. Good health, Cell biology, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, chemistry, Stem cell, Metabolic Networks and Pathways, metabolic shift
Abstract: 17 Pages, 5 figures, Control of stem cell fate to either enter terminal differentiation versus returning to quiescence (self-renewal) is crucial for tissue repair. Here, we showed that AMP-activated protein kinase (AMPK), the master metabolic regulator of the cell, controls muscle stem cell (MuSC) self-renewal. AMPKα1-/- MuSCs displayed a high self-renewal rate, which impairs muscle regeneration. AMPKα1-/- MuSCs showed a Warburg-like switch of their metabolism to higher glycolysis. We identified lactate dehydrogenase (LDH) as a new functional target of AMPKα1. LDH, which is a non-limiting enzyme of glycolysis in differentiated cells, was tightly regulated in stem cells. In functional experiments, LDH overexpression phenocopied AMPKα1-/- phenotype, that is shifted MuSC metabolism toward glycolysis triggering their return to quiescence, while inhibition of LDH activity rescued AMPKα1-/- MuSC self-renewal. Finally, providing specific nutrients (galactose/glucose) to MuSCs directly controlled their fate through the AMPKα1/LDH pathway, emphasizing the importance of metabolism in stem cell fate., This work was funded by grants from a European Commission integrated project (LSHM‐CT‐2004‐005272), the Framework Programme FP7 Endostem (under grant agreement 241440), the Association Française contre les Myopathies, Ligue Nationale Contre le Cancer, and the Société Française de Myologie. We thank D.G. Hardie (Dundee University, Scotland, UK) for providing antibodies against AMPKα1, R.A. Depinho (University of Texas, Austin, TX) for providing the LKB1fl/fl mice, Pierre Rocheteau for providing antibody against TOM22 (Institut Pasteur, Paris, France), T. Andrieu and S. Dussurgey from the AniRA‐Cytometry platform (UMS 3444—SFR Gerland Biosciences, Lyon, France) for their expertise in cell sorting, and Frederic Bouillaud for his expertise and help in bioenergetics and metabolism (Institut Cochin, Paris, France).
Published: 2017

37. GFAT1 phosphorylation by AMPK promotes VEGF-induced angiogenesis

Author: Cora Weigert, Kei Sakamoto, Katrin Spengler, Mark Peggie, Karina Mariño, Olga Göransson, Franck Vandermoere, Anne Knierim, Darya Zibrova, Benoit Viollet, Nicholas A. Morrice, Regine Heller, Jena University Hospital [Jena], Institut de Génomique Fonctionnelle (IGF), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS), Department of Experimental Medical Sciences [Lund, Sweden], Lund University [Lund], Division of Signal Transduction Therapy, University of Dundee, Instituto de Biología y Medicina Experimental [Buenos Aires] (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), Institut Cochin (UMR_S567 / UMR 8104), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), MRC Protein Phosphorylation & Ubiquitylation Unit, Sir James Black Centre and School of Life Science - Division of Cell Signalling and Immunology, Welcome Trust Building, University of Dundee, Dundee DD1 5EH, United Kingdom., Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)
Subjects: 0301 basic medicine, AMPK, Vascular Endothelial Growth Factor A, GFAT1, Angiogenesis, [SDV]Life Sciences [q-bio], AMP-Activated Protein Kinases, Biochemistry, Energy homeostasis, ANGIOGENESIS, chemistry.chemical_compound, Mice, 0302 clinical medicine, Serine, Phosphorylation, RNA, Small Interfering, Alanine, PHOSPHOPROTEOMICS, Bioquímica y Biología Molecular, VEGF, Cell biology, Vascular endothelial growth factor, Medicina Básica, medicine.anatomical_structure, AMPK, GFAT1, O-GlcNAcylation, VEGF, angiogenesis, phosphoproteomics, CIENCIAS MÉDICAS Y DE LA SALUD, Endothelium, Primary Cell Culture, O-GlcNACYLATION, Neovascularization, Physiologic, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Acetylglucosamine, 03 medical and health sciences, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Human Umbilical Vein Endothelial Cells, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Protein kinase A, Molecular Biology, Glutamine-Fructose-6-Phosphate Transaminase (Isomerizing), Hexosamines, Cell Biology, Fibroblasts, Ribonucleotides, Aminoimidazole Carboxamide, Phosphoproteins, Ampk, Gfat1, O-glcnacylation, Vegf, Phosphoproteomics, Glutamine, 030104 developmental biology, Glucose, chemistry, Amino Acid Substitution, Protein Processing, Post-Translational, 030217 neurology & neurosurgery
Abstract: Activation of AMP-activated protein kinase (AMPK) in endothelial cells regulates energy homeostasis, stress protection and angiogenesis, but the underlying mechanisms are incompletely understood. Using a label-free phosphoproteomic analysis, we identified glutamine:fructose-6-phosphate amidotransferase 1 (GFAT1) as an AMPK substrate. GFAT1 is the rate-limiting enzyme in the hexosamine biosynthesis pathway (HBP) and as such controls the modification of proteins by O-linked β-N-acetylglucosamine (O-GlcNAc). In the present study, we tested the hypothesis that AMPK controls O-GlcNAc levels and function of endothelial cells via GFAT1 phosphorylation using biochemical, pharmacological, genetic and in vitro angiogenesis approaches. Activation of AMPK in primary human endothelial cells by 5-aminoimidazole-4-carboxamide riboside (AICAR) or by vascular endothelial growth factor (VEGF) led to GFAT1 phosphorylation at serine 243. This effect was not seen when AMPK was down-regulated by siRNA. Upon AMPK activation, diminished GFAT activity and reduced O-GlcNAc levels were observed in endothelial cells containing wild-type (WT)-GFAT1 but not in cells expressing non-phosphorylatable S243A-GFAT1. Pharmacological inhibition or siRNA-mediated down-regulation of GFAT1 potentiated VEGF-induced sprouting, indicating that GFAT1 acts as a negative regulator of angiogenesis. In cells expressing S243A-GFAT1, VEGF-induced sprouting was reduced, suggesting that VEGF relieves the inhibitory action of GFAT1/HBP on angiogenesis via AMPK-mediated GFAT1 phosphorylation. Activation of GFAT1/HBP by high glucose led to impairment of vascular sprouting, whereas GFAT1 inhibition improved sprouting even if glucose level was high. Our findings provide novel mechanistic insights into the role of HBP in angiogenesis. They suggest that targeting AMPK in endothelium might help to ameliorate hyperglycaemia-induced vascular dysfunction associated with metabolic disorders. Fil: Zibrova, Darya. Universitat Jena; Alemania Fil: Vandermoere, Franck. Universite de Montpellier; Francia. Inserm; Francia Fil: Göransson, Olga. Lund University; Suecia Fil: Peggie, Mark. University of Dundee; Reino Unido Fil: Mariño, Karina Valeria. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental. Fundación de Instituto de Biología y Medicina Experimental. Instituto de Biología y Medicina Experimental; Argentina Fil: Knierim, Anne. Universitat Jena; Alemania Fil: Spengler, Katrin. Universitat Jena; Alemania Fil: Weigert, Cora. German Center For Diabetes Research ; Alemania. Universitat Tübingen; Alemania Fil: Viollet, Benoit. Inserm; Francia. Université Paris Descartes; Francia Fil: Morrice, Nicholas A.. AB-Sciex; Reino Unido Fil: Sakamoto, Kei. University Of Dundee; Fil: Heller, Regine. Universitat Jena; Alemania
Published: 2017

38. Experimental study of airflow and heat transfer above a hot liquid surface simulating a cup of drink

Author: Chr. Hartmann, Hong-Minh Hoang, C. Trelea, V. Osswald, Onrawee Laguerre, Denis Flick, Isabelle Souchon, Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Génie et Microbiologie des Procédés Alimentaires (GMPA), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], and Ingénierie, Procédés, Aliments (GENIAL)
Subjects: Convection, Work (thermodynamics), Materials science, Air, Airflow, Hot drink, Flow (psychology), Evaporation, Mechanical engineering, 04 agricultural and veterinary sciences, Heat transfer coefficient, Mechanics, 040401 food science, 6. Clean water, 0404 agricultural biotechnology, Heat transfer, Heat exchanger, [SDV.IDA]Life Sciences [q-bio]/Food engineering, [SPI.GPROC]Engineering Sciences [physics]/Chemical and Process Engineering, Food Science
Abstract: International audience; This work was carried out to study the airflow and heat transfer above a cup of hot drink. The experiment was undertaken in a device in which the air temperature and velocity were controlled representing a room condition. The influence of heat exchange by convection and evaporation between the hot drink (at different temperatures) and air on the velocity and temperature fields above the cup is presented. An experimental methodology was developed to evaluate the heat transfer coefficient between the air and hot drink with and without evaporation.The airflow visualisation by PIV (Particle Imagery Velocimetry) above the cup shows that the flow is complex with unsteady plumes detachment and vortex formation. The combined convection and evaporation lead to upward airflow with temperature fluctuations which become significant for drink temperature above 55 °C. This can be explained by the non-linearity between saturated pressure of water and its temperature. This work could highlight how volatile aromas are released from hot drink.
Published: 2017

39. Intestinal microbiota: what to expect physiologically and therapeutically?

Author: Dore, Joël, Multon, Marie-Christine, Behier, Jehan-Michel, Affagard, Herve, Andremont, Antoine, Barthelemy, Philippe, Batista, Rui, Bonneville, Marc, Bonny, Christophe, Boyaval, Gwendoline, Chamaillard, Mathias, Chevalier, Marie-Pierre, Cordaillat-Simmons, Magali, Cournarie, Fabienne, Diaz, Isabelle, Guillaume, Elisabeth, Guyard, Cyril, Jouvin-Marche, Evelyne, Martin, Francois-Pierre, Petiteau, David, MetaGenoPolis, Institut National de la Recherche Agronomique (INRA), Université Paris-Saclay, Sanofi, Takeda France, MaaT Pharma, Hôpital Bichat, Assistance Publique - Hôpitaux de Paris, Université Paris Diderot - Paris 7 (UPD7), AstraZeneca, CHU Cochin [AP-HP], Fondation Mérieux, Enterome Bioscience, Merck & Co. Inc, Centre d’Infection et d’Immunité de Lille (CIIL) - U1019 - 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 National de la Recherche Scientifique (CNRS), Réseau International des Instituts Pasteur (RIIP), Pfizer, Pharmabiotic Research Institute, Fondation IPSEN, Leem/ARIIS, Hop St Louis, BIOASTER, Immunologie, inflammation, infectiologie et microbiologie (I3M), Institut National de la Santé et de la Recherche Médicale (INSERM), Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], MaaT Pharma [Lyon], Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - 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 Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), BIOASTER Microbiology Technology Institute [Lyon], Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [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 National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), 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: stomatognathic diseases, fluids and secretions, [SDV]Life Sciences [q-bio], digestive system
Abstract: Intestinal microbiota: what to expect physiologically and therapeutically?
Published: 2017

40. Nuclear Proteomics Uncovers Diurnal Regulatory Landscapes in Mouse Liver

Author: Frédéric Gachon, Eva Martin, Loïc Dayon, Patrice Waridel, Manfredo Quadroni, Florian Atger, Jingkui Wang, Antonio Núñez Galindo, Martin Kussmann, Federico Sizzano, Felix Naef, Vjekoslav Dulic, Alessio Palini, Daniel Mauvoisin, Ecole Polytechnique Fédérale de Lausanne (EPFL), Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], University of Lausanne (UNIL), Institut de Génétique Moléculaire de Montpellier (IGMM), and Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)
Subjects: 0301 basic medicine, Proteomics, Resource, Time Factors, DNA Repair, Proteome, Transcription, Genetic, Physiology, Circadian clock, Ribosome biogenesis, Biology, Mass Spectrometry, Polyploidy, 03 medical and health sciences, Mice, Stable isotope labeling by amino acids in cell culture, Circadian Clocks, Transcriptional regulation, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Nuclear protein, Phosphorylation, Molecular Biology, Regulation of gene expression, Genetics, Cell Nucleus, Mice, Knockout, Organelle Biogenesis, Nuclear Proteins, Cell Biology, Phosphoproteins, Cell biology, Circadian Rhythm, Cell nucleus, 030104 developmental biology, medicine.anatomical_structure, Gene Expression Regulation, Liver, Isotope Labeling, Protein Kinases, Ribosomes, Transcription Factors
Abstract: Summary Diurnal oscillations of gene expression controlled by the circadian clock and its connected feeding rhythm enable organisms to coordinate their physiologies with daily environmental cycles. While available techniques yielded crucial insights into regulation at the transcriptional level, much less is known about temporally controlled functions within the nucleus and their regulation at the protein level. Here, we quantified the temporal nuclear accumulation of proteins and phosphoproteins from mouse liver by SILAC proteomics. We identified around 5,000 nuclear proteins, over 500 of which showed a diurnal accumulation. Parallel analysis of the nuclear phosphoproteome enabled the inference of the temporal activity of kinases accounting for rhythmic phosphorylation. Many identified rhythmic proteins were parts of nuclear complexes involved in transcriptional regulation, ribosome biogenesis, DNA repair, and the cell cycle and its potentially associated diurnal rhythm of hepatocyte polyploidy. Taken together, these findings provide unprecedented insights into the diurnal regulatory landscape of the mouse liver nucleus., Graphical Abstract, Highlights • SILAC nuclear proteomics uncovered new diurnal regulatory landscape of mouse liver • Regulation of the diurnal nuclear proteome is mostly post-translational • Diurnal proteins regulate transcription, ribosome biogenesis, DNA repair, and cell cycle • Hepatocyte polyploidy and size oscillate diurnally, Wang et al. quantify the temporal nuclear accumulation of proteins and phosphoproteins in the mouse liver and reveal that 13% of nuclear proteins exhibit a diurnal rhythm regulated at the post-translational level through nuclear transport of protein complexes involved in transcription, DNA repair, ribosome biogenesis, cell cycle, and polyploidy.
Published: 2017

41. Imputation de données manquantes pour l'inférence de r éseau à partir de données RNA-seq

Author: Imbert, Alyssa, Le Gall, Caroline, Armenise, Claudia, Lefebvre, Gregory, Hager, Jorg, Valsesia, Armand, Gourraud, Pierre-Antoine, Viguerie, Nathalie, Vialaneix, Nathalie, Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRA), Institut National de la Recherche Agronomique (INRA), Methodomics, Quartzbio, Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Institut des Maladies Métaboliques et Cardiovasculaires (I2MC), 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), Methodomics http://www.methodomics.comRégion Languedoc-Roussillon Midi-Pyrénées, and Vialaneix, Nathalie
Subjects: missing data, [STAT.AP]Statistics [stat]/Applications [stat.AP], [STAT.ME] Statistics [stat]/Methodology [stat.ME], [STAT.AP] Statistics [stat]/Applications [stat.AP], multiple imputation, [MATH.MATH-ST]Mathematics [math]/Statistics [math.ST], network, hot deck, imputation multiple, [MATH.MATH-ST] Mathematics [math]/Statistics [math.ST], [STAT.ME]Statistics [stat]/Methodology [stat.ME], réseau, données manquantes
Abstract: In this article, the issue of gene network inference is addressed, in which inference is performed from expression data obtained by RNA-seq sequencing technique. Our proposal aims at integrating external information (another kind of 'omic for instance) measured on the same individuals and on additional individuals. The method is presented as a missing data imputation problem and is solved with multiple hot deck approaches in order to infer a more stable network. Our results will be illustrated on real data coming from a paneuropean project on obesity., Dans cette proposition de communication, nous nous intéressons au problème de l'inférence de réseaux de gènes à partir de données d'expression mesurées par RNA-seq. Nous présentons une approche qui permet d'intégrer de l'information externe (autre type d'omic par exemple) obtenue sur les mêmes individus ainsi que sur d'autres individus. Notre approche est présentée comme un problème d'imputation que nous résolvons avec des approches de type "hot deck" multiple pour obtenir un réseau plus stable. Nous illustrerons nos résultats sur des données réelles issues d'un programme d'études sur l'obésité.
Published: 2016

42. Comparaison des apports alimentaires de sujets nés avec un petit poids de naissance versus ceux de poids normal dans la cohorte Haguenau

Author: Julien Bertrand, Estelle Pujos-Guillot, Blandine Comte, Sébastien Czernichow, Claire Levy-Marchal, Claire Carette, Joane Matta, Marie Zins, Mélanie Pétéra, UMS 011, Institut National de la Santé et de la Recherche Médicale (INSERM), Nutrition, Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Unité de Nutrition Humaine - Clermont Auvergne (UNH), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne (UCA), Vieillissement et Maladies chroniques : approches épidémiologique et de santé publique (VIMA), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), ProdInra, Archive Ouverte, Unité de Nutrition Humaine (UNH), Institut National de la Recherche Agronomique (INRA)-Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université, Société Francophone Nutrition Clinique et Métabolisme (SFNEP). FRA., Université d'Auvergne - Clermont-Ferrand I (UdA)-Clermont Université-Institut National de la Recherche Agronomique (INRA), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)
Subjects: 0303 health sciences, adulte, Nutrition and Dietetics, syndrome métabolique, 030309 nutrition & dietetics, Endocrinology, Diabetes and Metabolism, adult, poids à la naissance, metabolic x syndrome, birth weight, 03 medical and health sciences, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, 0302 clinical medicine, 030220 oncology & carcinogenesis, Alimentation et Nutrition, Internal Medicine, Food and Nutrition, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, apport alimentaire
Abstract: Introduction et but de l’étude: Contexte : Le petit poids de naissance a été associé à un risque accru de syndrome métabolique (SM) à l’âge adulte. Il a aussi été montré que les apports alimentaires pouvaient moduler le risque de SM. Cependant, il n’existe aucune donnée décrivant l’alimentation à l’âge adulte de sujets nés avec un petit poids de naissance (SGA) versus des sujets nés de poids normal (AGA). Objectif : Comparer l’apport alimentaire de sujets adultes nés SGA versus de sujets nés AGA. Matériel et méthodes: Design : Analyse transversale de données issues de la cohorte Haguenau. Participants : 172 adultes nés SGA et 229 adultes nés AGA parmi les 536 adultes de la cohorte ayant des données alimentaires disponibles. Les sujets étaient âgés de 22 ± 3,8 ans; 46% de sexe masculin avec un IMC moyen de 22,5 ± 3,9 kg/m². Méthodes: L’apport alimentaire a été calculé en se basant sur un questionnaire alimentaire de 19 items portant sur différents groupes d’aliments. Des analyses univariées ont été réalisées sur ces aliments. Des analyses de correspondances multiples ont été utilisées pour déterminer des typologies alimentaires. Un score d’adéquation alimentaire au Programme National Nutrition Santé (PNNS) a été calculé. Le score inclut 8 items, la valeur la plus basse correspondant à un apport alimentaire le moins en adéquation avec les recommandations. Les risques relatifs (IC 95%) dans le quartile 1 du score versus les quartiles 2, 3, et 4 chez les sujets nés SGA versus AGA ont été calculés. Résultats et Analyse statistique: Résultats : En analyses univariées, les sujets nés SGA consommaient moins de poisson (p=0.045) et plus de viande (p=0.034) et dessert (p=0.035) que les sujets nés AGA. Les analyses de correspondances multiples n’ont pas donné de résultats significatifs. Le risque relatif d’appartenir au quartile PNNS le plus bas chez les sujets SGA n’était pas significativement différent comparé à celui des sujets nés AGA ; RR= 0,94 (0,72; 1,23, avec et sans ajustement pour l’âge et le sexe). Conclusion: Conclusions : Cette étude est la première à comparer les apports alimentaires à l’âge adulte de sujets nés avec un petit poids de naissance versus ceux avec un poids normal. En dehors de différences minimes observées en analyse univariée, il n’a pas été retrouvé de différence sur les scores alimentaires définis a priori ou a posteriori. Ces résultats suggèrent que les paramètres associés à l’empreinte fœtale joueraient un rôle prépondérant dans le développement du SM à l’âge adulte. Cependant, d’autres études seraient nécessaires pour comprendre l’impact des apports alimentaires et de l’activité physique sur le statut métabolique des sujets nés SGA
Published: 2016

43. Six1 homeoprotein drives myofiber type IIA specialization in soleus muscle

Author: Serge Ducommun, Iori Sakakibara, Pascal Maire, Marc Santolini, Anthony Guernec, Matthieu Dos Santos, Maud Wurmser, Romain Davaze, Kei Sakamoto, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique Statistique de l'ENS (LPS), Université Paris Diderot - Paris 7 (UPD7)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS), Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Financial support was provided by the Institut National de la Santéet la Recherche Médicale (INSERM), the'Association Française contre lesMyopathies'(AFM), the Centre National de la Recherche Scientifique (CNRS),and the Agence Nationale pour la Recherche (ANR RPV09108KKA). We alsoacknowledge a contribution to the Institut Cochin animal care facility, madeby the Région Ile de France., Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris (FRDPENS), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), BMC, BMC, Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Physique Statistique de l'ENS ( LPS ), Fédération de recherche du Département de physique de l'Ecole Normale Supérieure - ENS Paris ( FRDPENS ), Centre National de la Recherche Scientifique ( CNRS ) -École normale supérieure - Paris ( ENS Paris ) -Centre National de la Recherche Scientifique ( CNRS ) -École normale supérieure - Paris ( ENS Paris ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Nestlé Institute of Health Sciences SA [Lausanne, Suisse], EPFL Innovation Park [Lausanne, Suisse], Institut Cochin, Université Sorbonne Paris Cité (USPC) - Université Paris Descartes - Paris 5 (UPD5) - Centre National de la Recherche Scientifique (CNRS) - Institut National de la Santé et de la Recherche Médicale (INSERM), Division of Integrative Pathophysiology [Ehime, Japan], Ehime University [Japan], and Centre National de la Recherche Scientifique (CNRS) - Université Paris Diderot - Paris 7 (UP7) - École normale supérieure - Paris (ENS Paris) - Université Pierre et Marie Curie - Paris 6 (UPMC)
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Six1, Pvalb, [SDV]Life Sciences [q-bio], Muscle Fibers, Skeletal, Calcium buffering, Skeletal muscle, Biology, Mice, 03 medical and health sciences, Soleus, Internal medicine, Myosin, Gene expression, Slow and fast myofibers, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, medicine, Animals, Myocyte, Gene Regulatory Networks, Orthopedics and Sports Medicine, Molecular Biology, Transcription factor, Homeodomain Proteins, Soleus muscle, [ SDV ] Life Sciences [q-bio], Myosin Heavy Chains, Research, Cell Biology, [SDV] Life Sciences [q-bio], Phenotype, 030104 developmental biology, medicine.anatomical_structure, Endocrinology, Myogenic regulatory factors, Calcium, Transcriptome, Myosin heavy chain, Glycolysis, Gene Deletion
Abstract: Background Adult skeletal muscles are composed of slow and fast myofiber subtypes which each express selective genes required for their specific contractile and metabolic activity. Six homeoproteins are transcription factors regulating muscle cell fate through activation of myogenic regulatory factors and driving fast-type gene expression during embryogenesis. Results We show here that Six1 protein accumulates more robustly in the nuclei of adult fast-type muscles than in adult slow-type muscles, this specific enrichment takes place during perinatal growth. Deletion of Six1 in soleus impaired fast-type myofiber specialization during perinatal development, resulting in a slow phenotype and a complete lack of Myosin heavy chain 2A (MyHCIIA) expression. Global transcriptomic analysis of wild-type and Six1 mutant myofibers identified the gene networks controlled by Six1 in adult soleus muscle. This analysis showed that Six1 is required for the expression of numerous genes encoding fast-type sarcomeric proteins, glycolytic enzymes and controlling intracellular calcium homeostasis. Parvalbumin, a key player of calcium buffering, in particular, is a direct target of Six1 in the adult myofiber. Conclusions This analysis revealed that Six1 controls distinct aspects of adult muscle physiology in vivo, and acts as a main determinant of fast-fiber type acquisition and maintenance. Electronic supplementary material The online version of this article (doi:10.1186/s13395-016-0102-x) contains supplementary material, which is available to authorized users.
Published: 2015

44. MARK-AGE biomarkers of ageing

Author: Jürgen Bernhard, Mikko Hurme, P. Eline Slagboom, Paola Caiafa, Tilman Grune, Alexander Bürkle, Olivier Toussaint, Michel Salmon, Daniela Gradinaru, Eugenio Mocchegiani, Efstathios S. Gonos, Ewa Sikora, Antti Hervonen, Claudio Franceschi, Peter Kristensen, Martijn E.T. Dollé, Sebastiano Collino, Beatrix Grubeck-Loebenstein, Maria A. Blasco, Duncan Talbot, Andreas Simm, Richard Aspinall, Claude Libert, Helen R. Griffiths, Jan H.J. Hoeijmakers, Gerben Zondag, Bertrand Friguet, Miriam Capri, Nicolle Breusing, Maria Moreno-Villanueva, University of Konstanz, BioTeSys GmbH, Esslingen, Spanish National Cancer Research Center (CNIO), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Université de Namur [Namur] (UNamur), Institute for Biomedical Aging Research, University of Innsbruck, Translational Research Center of Nutrition and Ageing (IRCCS-INRCA), Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], National Hellenic Research Foundation, Nencki Institute of Experimental Biology, National Institute of Geriatrics and Gerontology 'Ana Aslan', National Institute for Public Health and the Environment [Bilthoven] (RIVM), Straticell, Science Park Crealys, Department of Engineering – BCE Protein Engineering, School of Life and Health Sciences, Aston University [Birmingham], Department for Molecular Biomedical Research (DFMBR), Universiteit Gent = Ghent University [Belgium] (UGENT)-VIB, University of Hohenheim, Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany], University Hospital Halle, CIG - Interdepartmental Center 'L.Galvani', Leiden University Medical Center (LUMC), Department of Cellular Biotechnologies and Hematology, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Medical School, University of Tampere [Finland], The MARK-AGE project has received funding from the European Union’s FP7 research and innovation programme under grant agreement HEALTH-F4-2008-200880, European Project: 200880,EC:FP7:HEALTH,FP7-HEALTH-2007-A,MARK-AGE(2008), Leopold Franzens Universität Innsbruck - University of Innsbruck, Universiteit Gent = Ghent University (UGENT)-VIB, Universiteit Leiden, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome] (UNIROMA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Bürkle, Alexander, Moreno-Villanueva, María, Bernhard, Jürgen, Blasco, María, Zondag, Gerben, Hoeijmakers, Jan H.J., Toussaint, Olivier, Grubeck-Loebenstein, Beatrix, Mocchegiani, Eugenio, Collino, Sebastiano, Gonos, Efstathios S., Sikora, Ewa, Gradinaru, Daniela, Dollé, Martijn, Salmon, Michel, Kristensen, Peter, Griffiths, Helen R., Libert, Claude, Grune, Tilman, Breusing, Nicolle, Simm, Andrea, Franceschi, Claudio, Capri, Miriam, Talbot, Duncan, Caiafa, Paola, Friguet, Bertrand, Slagboom, P. Eline, Hervonen, Antti, Hurme, Mikko, Aspinall, Richard, Molecular Genetics, Spanish National Cancer Research Centre (CNIO), Université de Namur [Namur], Ghent University [Belgium] (UGENT)-VIB, Friedrich-Schiller-Universität Jena, Università degli Studi di Roma 'La Sapienza' [Rome], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, Gerontology, Aging, MITOCHONDRIAL-DNA, Biological age, Single measurement, Scientific literature, Biology, 03 medical and health sciences, OLD-AGE, 0302 clinical medicine, Ageing biomarker, T-CELL SUBSETS, ddc:570, Humans, Ageing biomarkers, European commission, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, European Union, OXIDATIVE STRESS, 030304 developmental biology, Genetics, 0303 health sciences, INDUCED PREMATURE SENESCENCE, Human studies, Biology and Life Sciences, Human studie, APOLIPOPROTEIN-E GENOTYPE, REPLICATIVE SENESCENCE, MARK-AGE, Ageing, C-REACTIVE-PROTEIN, Human longevity, TELOMERE LENGTH, Female, Biomarkers, HUMAN LONGEVITY, 030217 neurology & neurosurgery, Developmental Biology
Abstract: Many candidate biomarkers of human ageing have been proposed in the scientific literature but in all cases their variability in cross-sectional studies is considerable, and therefore no single measurement has proven to serve a useful marker to determine, on its own, biological age. A plausible reason for this is the intrinsic multi-causal and multi-system nature of the ageing process. The recently completed MARK-AGE study was a large-scale integrated project supported by the European Commission. The major aim of this project was to conduct a population study comprising about 3200 subjects in order to identify a set of biomarkers of ageing which, as a combination of parameters with appropriate weighting, would measure biological age better than any marker in isolation. (C) 2015 The Authors. Published by Elsevier Ireland Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Published: 2015

45. AMPKα1 Regulates Macrophage Skewing at the Time of Resolution of Inflammation during Skeletal Muscle Regeneration.: AMPKα1 regulates macrophage skewing

Author: Kei Sakamoto, Bénédicte Chazaud, Marine Theret, Benoit Viollet, Ludovic Arnold, Rémi Mounier, Olga Göransson, Laurent Bultot, Marc Foretz, Sylvain Cuvellier, Arnaud Ferry, Nieves Sanz, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immunité et Infection, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Department of Experimental Medical Sciences [Lund, Sweden], Lund University [Lund], Institut de Myologie, Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Cochin ( UM3 (UMR 8104 / U1016) ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -IFR113-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Nutrition, Nestlé Institute of Health Sciences SA, Department of Experimental Medical Sciences, Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Assistance publique - Hôpitaux de Paris (AP-HP)-Association française contre les myopathies ( AFM-Téléthon ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), and Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Association française contre les myopathies (AFM-Téléthon)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Pierre et Marie Curie - Paris 6 (UPMC)
Subjects: Male, AMPK, Physiology, Macrophage, Phagocytosis, Cell, Inflammation, Apoptosis, Calcium-Calmodulin-Dependent Protein Kinase Kinase, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, AMP-Activated Protein Kinases, Proinflammatory cytokine, 03 medical and health sciences, Mice, 0302 clinical medicine, skeletal muscle regeneration, medicine, Leukocytes, Animals, Regeneration, Muscle, Skeletal, Molecular Biology, Cells, Cultured, 030304 developmental biology, Mice, Knockout, resolution of inflammation, 0303 health sciences, [ SDV.BC ] Life Sciences [q-bio]/Cellular Biology, Macrophages, Skeletal muscle, phagocytosis, Cell Biology, Macrophage Activation, Phenotype, Cell biology, medicine.anatomical_structure, medicine.symptom, 030217 neurology & neurosurgery, Signal Transduction
Abstract: International audience; Macrophages control the resolution of inflammation through the transition from a proinflammatory (M1) to an anti-inflammatory (M2) phenotype. Here, we present evidence for a role of AMPKα1, a master regulator of energy homeostasis, in macrophage skewing that occurs during skeletal muscle regeneration. Muscle regeneration was impaired in AMPKα1(-/-) mice. In vivo loss-of-function (LysM-Cre;AMPKα1(fl/fl) mouse) and rescue (bone marrow transplantation) experiments showed that macrophagic AMPKα1 was required for muscle regeneration. Cell-based experiments revealed that AMPKα1(-/-) macrophages did not fully acquire the phenotype or the functions of M2 cells. In vivo, AMPKα1(-/-) leukocytes did not acquire the expression of M2 markers during muscle regeneration. Skewing from M1 toward M2 phenotype upon phagocytosis of necrotic and apoptotic cells was impaired in AMPKα1(-/-) macrophages and when AMPK activation was prevented by the inhibition of its upstream activator, CaMKKβ. In conclusion, AMPKα1 is crucial for phagocytosis-induced macrophage skewing from a pro- to anti-inflammatory phenotype at the time of resolution of inflammation.
Published: 2013

46. AMPKα1 Regulates Macrophage Skewing at the Time of Resolution of Inflammation during Skeletal Muscle Regeneration

Author: Mounier, Rémi, Théret, Marine, Arnold, Ludovic, Cuvellier, Sylvain, Bultot, Laurent, Göransson, Olga, Sanz, Nieves, Ferry, Arnaud, Sakamoto, Kei, Foretz, Marc, Viollet, Benoit, Chazaud, Bénédicte, Chazaud, Benedicte, Institut Cochin (IC UM3 (UMR 8104 / U1016)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immunité et Infection, Université Pierre et Marie Curie - Paris 6 (UPMC)-IFR113-Institut National de la Santé et de la Recherche Médicale (INSERM), Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Department of Experimental Medical Sciences [Lund, Sweden], Lund University [Lund], Institut de Myologie, and Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Association française contre les myopathies (AFM-Téléthon)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: AMPK, resolution of inflammation, Macrophage, skeletal muscle regeneration, phagocytosis, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, [SDV.BC] Life Sciences [q-bio]/Cellular Biology
Abstract: International audience; Macrophages control the resolution of inflammation through the transition from a proinflammatory (M1) to an anti-inflammatory (M2) phenotype. Here, we present evidence for a role of AMPKα1, a master regulator of energy homeostasis, in macrophage skewing that occurs during skeletal muscle regeneration. Muscle regeneration was impaired in AMPKα1(-/-) mice. In vivo loss-of-function (LysM-Cre;AMPKα1(fl/fl) mouse) and rescue (bone marrow transplantation) experiments showed that macrophagic AMPKα1 was required for muscle regeneration. Cell-based experiments revealed that AMPKα1(-/-) macrophages did not fully acquire the phenotype or the functions of M2 cells. In vivo, AMPKα1(-/-) leukocytes did not acquire the expression of M2 markers during muscle regeneration. Skewing from M1 toward M2 phenotype upon phagocytosis of necrotic and apoptotic cells was impaired in AMPKα1(-/-) macrophages and when AMPK activation was prevented by the inhibition of its upstream activator, CaMKKβ. In conclusion, AMPKα1 is crucial for phagocytosis-induced macrophage skewing from a pro- to anti-inflammatory phenotype at the time of resolution of inflammation.
Published: 2013

47. The cAMP response element binding protein-2 (CREB-2) can interact with the C/EBP-homologous protein (CHOP)

Author: Jean-Michel Mesnard, Joseph Aman Koffi, Sabine Thébault, Jihane Basbous, Frédéric Gachon, Christian Devaux, Gilles Gaudray, Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Infections rétrovirales et signalisation cellulaire (IRSC), Université Montpellier 1 (UM1)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie moléculaire des plantes (IBMP), and Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)
Subjects: Transcription, Genetic, [SDV]Life Sciences [q-bio], Biochemistry, 0302 clinical medicine, Structural Biology, hemic and lymphatic diseases, Chlorocebus aethiops, cAMP response element binding protein-2, Promoter Regions, Genetic, ComputingMilieux_MISCELLANEOUS, Human T-cell leukemia virus type I, Transcription Factor CHOP, Human T-lymphotropic virus 1, 0303 health sciences, Ccaat-enhancer-binding proteins, biology, Chemistry, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, 030220 oncology & carcinogenesis, Basic leucine zipper factor, COS Cells, Gene Products, tat, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, tat Gene Products, Human Immunodeficiency Virus, CREB1, Gene Expression Regulation, Viral, Leucine zipper, Recombinant Fusion Proteins, Biophysics, Saccharomyces cerevisiae, CREB, cAMP response element site, Cell Line, 03 medical and health sciences, Two-Hybrid System Techniques, Genetics, Animals, Humans, C/EBP-homologous protein, Molecular Biology, CAMP response element binding, 030304 developmental biology, Cell Nucleus, Leucine Zippers, ATF3, Activator (genetics), Cell Biology, Activating Transcription Factor 4, Molecular biology, CCAAT-Enhancer-Binding Proteins, HIV-1, biology.protein, Transcription Factors
Abstract: cAMP response element binding protein-2 (CREB-2) is a basic leucine zipper (bZIP) factor that was originally described as a repressor of CRE-dependent transcription but that can also act as a transcriptional activator. Moreover, CREB-2 is able to function in association with the viral Tax protein as an activator of the human T-cell leukemia virus type I (HTLV-I) promoter. Here we show that CREB-2 is able to interact with C/EBP-homologous protein (CHOP), a bZIP transcription factor known to inhibit CAAT/enhancer-dependent transcription. Cotransfection of CHOP with CREB-2 results in decreased activation driven by the cellular CRE motif or the HTLV-I proximal Tax-responsive element, confirming that CREB-2 and CHOP can interact with each other in vivo.
Published: 2001

48. An inter-laboratory comparison of physiological and genetic properties of four Saccharomyces cerevisiae strains

Author: J Vindeløv, H.C Lange, Jean Luc Parrou, J.P. Van Dijken, Luca Brambilla, H. Y. Steensma, Jens Nielsen, Mike Hoare, Peter Niederberger, P Duboc, Matthias Reuss, N.A.W. van Riel, Manfred Rizzi, Jack T. Pronk, M. L. F. Giuseppin, CT Verrips, Danilo Porro, E.A Madden, J. Bauer, Carlos Gancedo, Thomas Petit, J. J. Heijnen, Jean Marie François, Van Dijken, J, Bauer, J, Brambilla, L, Duboc, P, Francois, J, Gancedo, C, Giuseppin, M, Heijnen, J, Hoare, M, Lange, H, Madden, E, Niederberger, P, Nielsen, J, Parrou, J, Petit, T, Porro, D, Reuss, M, Van Riel, N, Rizzi, M, Steensma, H, Verrips, C, Vindelov, J, Pronk, J, Department of Biotechnology [Delft], Delft University of Technology (TU Delft), Nestlé Institute of Health Sciences SA [Lausanne, Switzerland], Centre de Bioingénierie Gilbert Durand, Laboratoire Biotechnologie et Bioprocédés (LBB), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Instituto de Investigaciones Biomédicas Alberto Sols [Madrid, Spain] (IIBM), Universidad Autónoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), project 'From Gene to Product in Yeast: a Quantitative Approach,' subsidized by the European Community (EC Framework IV Cell Factory Program)., Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Spain] (CSIC), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), and Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-Universidad Autonoma de Madrid (UAM)
Subjects: [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Physiology, Auxotrophy, Bicine, Saccharomyces cerevisiae, Bioengineering, reference strain, Chemostat, Ethanol fermentation, Biology, Applied Microbiology and Biotechnology, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, Engineering, Genetics, saccharomyces cerevisiae, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, 030304 developmental biology, 0303 health sciences, 030306 microbiology, biology.organism_classification, Yeast, chemistry, Strain choice, Fermentation, Biotechnology, Transformation efficiency
Abstract: International audience; To select a Saccharomyces cerevisiae reference strain amenable to experimental techniques used in (molecular) genetic, physiological and biochemical engineering research, a variety of properties were studied in four diploid, prototrophic laboratory strains. The following parameters were investigated: 1) maximum specific growth rate in shake-flask cultures; 2) biomass yields on glucose during growth on defined media in batch cultures and steady-state chemostat cultures under controlled conditions with respect to pH and dissolved oxygen concentration; 3) the critical specific growth rate above which aerobic fermentation becomes apparent in glucose-limited accelerostat cultures; 4) sporulation and mating efficiency; and 5) transformation efficiency via the lithium-acetate, bicine, and electroporation methods. On the basis of physiological as well as genetic properties, strains from the CEN.PK family were selected as a platform for cell-factory research on the stoichiometry and kinetics of growth and product formation.
Published: 2000

49. Deficient Endoplasmic Reticulum-Mitochondrial Phosphatidylserine Transfer Causes Liver Disease.

Author: Hernández-Alvarez MI, Sebastián D, Vives S, Ivanova S, Bartoccioni P, Kakimoto P, Plana N, Veiga SR, Hernández V, Vasconcelos N, Peddinti G, Adrover A, Jové M, Pamplona R, Gordaliza-Alaguero I, Calvo E, Cabré N, Castro R, Kuzmanic A, Boutant M, Sala D, Hyotylainen T, Orešič M, Fort J, Errasti-Murugarren E, Rodrígues CMP, Orozco M, Joven J, Cantó C, Palacin M, Fernández-Veledo S, Vendrell J, and Zorzano A
Subjects: Animals, Disease Models, Animal, Endoplasmic Reticulum metabolism, Endoplasmic Reticulum Stress physiology, Hepatocytes metabolism, Hepatocytes pathology, Humans, Inflammation metabolism, Liver pathology, Liver Diseases etiology, Liver Diseases metabolism, Male, Mice, Mice, Inbred C57BL, Mitochondria metabolism, Primary Cell Culture, Protein Transport physiology, Signal Transduction, Triglycerides metabolism, GTP Phosphohydrolases metabolism, Mitochondrial Proteins metabolism, Non-alcoholic Fatty Liver Disease metabolism, Phosphatidylserines metabolism
Abstract: Non-alcoholic fatty liver is the most common liver disease worldwide. Here, we show that the mitochondrial protein mitofusin 2 (Mfn2) protects against liver disease. Reduced Mfn2 expression was detected in liver biopsies from patients with non-alcoholic steatohepatitis (NASH). Moreover, reduced Mfn2 levels were detected in mouse models of steatosis or NASH, and its re-expression in a NASH mouse model ameliorated the disease. Liver-specific ablation of Mfn2 in mice provoked inflammation, triglyceride accumulation, fibrosis, and liver cancer. We demonstrate that Mfn2 binds phosphatidylserine (PS) and can specifically extract PS into membrane domains, favoring PS transfer to mitochondria and mitochondrial phosphatidylethanolamine (PE) synthesis. Consequently, hepatic Mfn2 deficiency reduces PS transfer and phospholipid synthesis, leading to endoplasmic reticulum (ER) stress and the development of a NASH-like phenotype and liver cancer. Ablation of Mfn2 in liver reveals that disruption of ER-mitochondrial PS transfer is a new mechanism involved in the development of liver disease., (Copyright © 2019. Published by Elsevier Inc.)
Published: 2019
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50. Antioxidants linked with physical, cognitive and psychological frailty: Analysis of candidate biomarkers and markers derived from the MARK-AGE study.

Author: Rietman ML, Spijkerman AMW, Wong A, van Steeg H, Bürkle A, Moreno-Villanueva M, Sindlinger T, Franceschi C, Grubeck-Loebenstein B, Bernhardt J, Slagboom PE, Toussaint O, Debacq-Chainiaux F, Sikora E, Gonos ES, Breusing N, Stuetz W, Weber D, Grune T, Basso A, Piacenza F, Malavolta M, Collino S, Jansen EHJM, Verschuren WMM, and Dollé MET
Subjects: Adult, Aged, Biomarkers blood, Female, Humans, Male, Middle Aged, Adaptation, Psychological, Antioxidants metabolism, Beta-Cryptoxanthin blood, Cognitive Aging, Zeaxanthins blood
Abstract: Frailty among elderly people leads to an increased risk for negative health outcomes. To prevent frailty, we need a better understanding of the underlying mechanisms and early detection of individuals at risk. Both may be served by identifying candidate (bio)markers, i.e. biomarkers and markers, for the physical, cognitive, and psychological frailty domains. We used univariate (Rank-ANOVA) and multivariate (elastic net) approaches on the RASIG study population (age range: 35-74 years, n = 2220) of the MARK-AGE study to study up to 331 (bio)markers between individuals with and without frailty for each domain. Biomarkers and markers identified by both approaches were studied further regarding their association with frailty using logistic regression. Univariately, we found lower levels of antioxidants, including β-cryptoxanthin and zeaxanthin, in those who were physically, cognitively or psychologically frail. Additionally, self-reported health was worse in these three frail groups. Multivariately, we observed lower levels of β-cryptoxanthin and zeaxanthin in the cognitively frail. Levels of these carotenoids were inversely associated with the risk of being cognitively frail after adjusting for confounders. Antioxidants and self-reported health are potential (bio)markers to detect persons at risk of becoming frail. The biomarkers identified may indicate the involvement of inflammation in frailty, especially for physical and cognitive frailty., (Copyright © 2018 Elsevier B.V. All rights reserved.)
Published: 2019
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