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36 results on '"Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT)"'

1. CD44v3 is a marker of invasive cancer stem cells driving metastasis in gastric carcinoma

Author: Julie Giraud, Lornella Seeneevassen, Benoit Rousseau, Damien Bouriez, Elodie Sifré, Alban Giese, Tra Ly Nguyen, Camille Tiffon, Yannick Lippi, Lamia Azzi-Martin, Julie Pannequin, Armelle Ménard, Emilie Bessède, Cathy Staedel, Francis Mégraud, Geneviève Belleannée, Philippe Lehours, Caroline Gronnier, Pierre Dubus, Christine Varon, BoRdeaux Institute in onCology (Inserm U1312 - BRIC), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB), Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], 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), Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Régulations Naturelles et Artificielles (ARNA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Bordeaux Ségalen [Bordeaux 2], Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, French ‘Institut National du Cancer’ (PLBio INCa, grant number 2014-152), La Ligue contre le Cancer (C Tiffon PhD salary, regional research grants comité Dordogne grant number R17013GG and comité Gironde grant number GM/12.17/37), UFR des sciences médicales Univ. Bordeaux (J Giraud and D Bouriez financial support), French ministry of national education, research and technologies (L Seeneevassen PhD salary)., and LESUR, Hélène
Subjects: [SDV] Life Sciences [q-bio], Cancer Research, [SDV.CAN] Life Sciences [q-bio]/Cancer, Oncology, Cancer stem cells, Metastasis initiating cells, [SDV]Life Sciences [q-bio], Gastroenterology, [SDV.CAN]Life Sciences [q-bio]/Cancer, General Medicine, CD44 variant, Epithelial-mesenchymal transition, Gastric cancer
Abstract: Background Cancer stem cells (CSCs) are at the origin of tumour initiation and progression in gastric adenocarcinoma (GC). However, markers of metastasis-initiating cells remain unidentified in GC. In this study, we characterized CD44 variants expressed in GC and evaluated the tumorigenic and metastatic properties of CD44v3+ cells and their clinical significance in GC patients. Methods Using GC cell lines and patient-derived xenografts, we evaluated CD44+ and CD44v3+ GC cells molecular signature and their tumorigenic, chemoresistance, invasive and metastatic properties, and expression in patients-derived tissues. Results CD44v3+ cells, which represented a subpopulation of CD44+ cells, were detected in advanced preneoplastic lesions and presented CSCs chemoresistance and tumorigenic properties in vitro and in vivo. Molecular and functional analyses revealed two subpopulations of gastric CSCs: CD44v3+ CSCs with an epithelial-mesenchymal transition (EMT)-like signature, and CD44+/v3– CSCs with an epithelial-like signature; both were tumorigenic but CD44v3+ cells showed higher invasive and metastatic properties in vivo. CD44v3+ cells detected in the primary tumours of GC patients were associated with a worse prognosis. Conclusion CD44v3 is a marker of a subpopulation of CSCs with metastatic properties in GC. The identification of metastasis-initiating cells in GC represents a major advance for further development of anti-metastatic therapeutic strategies.
Published: 2022

2. Identification of bacterial lipo-amino acids: origin of regenerated fatty acid carboxylate from dissociation of lipo-glutamate anion

Author: Amandine Hueber, Yves Gimbert, Geoffrey Langevin, Jean-Marie Galano, Alexandre Guy, Thierry Durand, Nicolas Cenac, Justine Bertrand-Michel, Jean-Claude Tabet, Gestionnaire, HAL Sorbonne Université 5, MetaboHUB-MetaToul, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), 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-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 Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Recherche en Santé Digestive (IRSD ), Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de Chimie Moléculaire (DCM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Institut Parisien de Chimie Moléculaire (IPCM), Chimie Moléculaire de Paris Centre (FR 2769), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Université de Montpellier (UM), Inserm, PhD Grant, Région Occitanie, PhD Grant, MetaToul-MetaboHUB, Institut de Chimie du CNRS (INC)-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)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Anions, Spectrometry, Mass, Electrospray Ionization, Tandem mass spectrometry, Lipidomic, Ion-dipole Abbreviations ACN Acetonitrile CID Collision-induced dissociation DCM Dichloromethane DFT Density functional theory EcN Escherichia coli ESI Electrospray, Fatty Acids, Organic Chemistry, Clinical Biochemistry, Lipoamino acid, Glutamic Acid, Biochemistry, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Humans, Regeneration, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Amino Acids
Abstract: The identification of bacterial metabolites produced by the microbiota is a key point to understand its role in human health. Among them, lipo-amino acids (LpAA), which are able to cross the epithelial barrier and to act on the host, are poorly identified. Structural elucidation of few of them was performed by high-resolution tandem mass spectrometry based on electrospray combined with selective ion dissociations reach by collision-induced dissociation (CID). The negative ions were used for their advantages of yielding only few fragment ions sufficient to specify each part of LpAA with sensitivity. To find specific processes that help structural assignment, the negative ion dissociations have been scrutinized for an LpAA: the N-palmitoyl acyl group linked to glutamic acid (C16Glu). The singular behavior of [C16Glu-H]¯ towards CID showed tenth product ions, eight were described by expected fragment ions. In contrast, instead of the expected product ions due to CONH-CH bond cleavage, an abundant complementary dehydrated glutamic acid and fatty acid anion pair were observed. Specific to glutamic moiety, they were formed by a stepwise dissociation via molecular isomerization through ion–dipole formation prior to dissociation. This complex dissociated by partner splitting either directly or after inter-partner proton transfer. By this pathway, surprising regeneration of deprotonated fatty acid takes place. Such regeneration is comparable to that occurred from dissociation to peptides containing acid amino-acid. Modeling allow to confirm the proposed mechanisms explaining the unexpected behavior of this glutamate conjugate.
Published: 2022

3. Boot camp approach to surgical residency preparation: feedback from a French university hospital

Author: Etienne Buscail, Fabrice Muscari, Aurélien Hostalrich, Manon Bolzinger, Sandra Malavaud, Vincent Minville, Charlotte Martin, Magali Delhoste, Charles Henri Houze-Cerfon, Simon Buscail, Bruno Bastiani, Mathieu Roumiguié, Ariane Weyl, Nicolas Carrère, Olivier Abbo, Institut de Recherche en Santé Digestive (IRSD ), 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-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), The Toulouse Bar Association, Toulouse Institute for Health Stimulation, and SEGUIN, Nathalie
Subjects: Male, Medical student education, Preparedness surgical residency, [SHS.STAT]Humanities and Social Sciences/Methods and statistics, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Students, Medical, Surgical skills, [SHS.EDU]Humanities and Social Sciences/Education, [SHS.EDU] Humanities and Social Sciences/Education, Surgical residency program in France, Internship and Residency, General Medicine, Curriculum design, Feedback, Education, Hospitals, University, Video-based learning, [SHS.STAT] Humanities and Social Sciences/Methods and statistics, Humans, Surgery, Female, Educational Measurement, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Introduction The transition from medical student to surgical resident is not a simple one. The aim of this study was to report the experience of a university hospital in the organization of the induction course for future surgical residents and the contribution of a video support in the learning of the suture. Material and method We were able to study two consecutive years of students (October 2020 and 2021). Concerning the practical and technical workshops (learning suture) we carried out a comparative study between two groups of students. A group that had video support for learning suture (video group) and a group without video (control group). The evaluation of the suture was performed in a blinded manner by two supervising surgeons. The other practical workshop was drain fixation; the students did not have a video for this workshop. A comparative study was also performed for the drain fixation workshop between the two groups (video group and control group). A program of theoretical courses was also set up. This program is established according to the different future functions of the residents by integrating medico-legal notions and teamwork. Satisfaction questionnaires were given to the students and the answers were given two months after taking up their duties in the hospital (6 questions with Likert scale and 4 free questions). Results The cohort consisted of 58 students (29 each in 2020 and 29 in 2021). Comparative analyses of the evaluation of the suture workshops showed better performance in the video group compared with the group without video. The comparison of these two groups did not show significant differences in the drain fixation workshop. The theoretical teaching was broken down according to the students' future tasks and each speaker was a specialist in his or her field of expertise. The results of the questionnaires showed a desire on the part of the students to increase the time spent on practical workshops and theoretical forensic teaching. Conclusion We were able to show through these two years of a program that we were able to offer a surgical resident preparation course. In addition, we have highlighted the contribution of a video support in the learning curve of the suture.
Published: 2022

4. An optimization method for untargeted MS-based isotopic tracing investigations of metabolism

Author: Noémie Butin, Cécilia Bergès, Jean-Charles Portais, Floriant Bellvert, Geroscience and rejuvenation research center (RESTORE), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Toulouse Biotechnology Institute (TBI), 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 Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-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 Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-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 Paul Sabatier, Toulouse, France, Astruc, Suzette, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-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 Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Untargeted analysis, LC, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, MS, Biochemistry, Mass Spectrometry, [SDV] Life Sciences [q-bio], Parameter optimization, Isotope Labeling, Isotope labelling experiments, Escherichia coli, Metabolomics, Chromatography, Liquid
Abstract: Introduction Stable isotope tracer studies are increasingly applied to explore metabolism from the detailed analysis of tracer incorporation into metabolites. Untargeted LC/MS approaches have recently emerged and provide potent methods for expanding the dimension and complexity of the metabolic networks that can be investigated. A number of software tools have been developed to process the highly complex MS data collected in such studies; however, a method to optimize the extraction of valuable isotopic data is lacking. Objectives To develop and validate a method to optimize automated data processing for untargeted MS-based isotopic tracing investigations of metabolism. Methods The method is based on the application of a suitable reference material to rationally perform parameter optimization throughout the complete data processing workflow. It was applied in the context of 13C-labelling experiments and with two different software, namely geoRge and X13CMS. It was illustrated with the study of a E. coli mutant impaired for central metabolism. Results The optimization methodology provided significant gain in the number and quality of extracted isotopic data, independently of the software considered. Pascal triangle samples are well suited for such purpose since they allow both the identification of analytical issues and optimization of data processing at the same time. Conclusion The proposed method maximizes the biological value of untargeted MS-based isotopic tracing investigations by revealing the full metabolic information that is encoded in the labelling patterns of metabolites.
Published: 2022

5. Curcumin and NCLX inhibitors share anti-tumoral mechanisms in microsatellite-instability-driven colorectal cancer

Author: Maxime Guéguinou, Sajida Ibrahim, Jérôme Bourgeais, Alison Robert, Trayambak Pathak, Xuexin Zhang, David Crottès, Jacques Dupuy, David Ternant, Valérie Monbet, Roseline Guibon, Hector Flores-Romero, Antoine Lefèvre, Stéphanie Lerondel, Alain Le Pape, Jean-François Dumas, Philippe G. Frank, Alban Girault, Romain Chautard, Françoise Guéraud, Ana J. García-Sáez, Mehdi Ouaissi, Patrick Emond, Olivier Sire, Olivier Hérault, Gaëlle Fromont-Hankard, Christophe Vandier, David Tougeron, Mohamed Trebak, William Raoul, Thierry Lecomte, Nutrition, croissance et cancer (U 1069) (N2C), Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT), ERL 7001 LNOx (Leukemic Niche & redOx metabolism / Niche leucémique et métabolisme redOx) (LNOx), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre National de la Recherche Scientifique (CNRS)-Microenvironnement des niches tumorales (CNRS GDR 3697 Micronit ), 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)-Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT)-Université de Tours (UT), Pennsylvania State University (Penn State), Penn State System, Prévention et promotion de la cancérogénèse par les aliments (ToxAlim-PPCA), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), EA4245 - Transplantation, Immunologie, Inflammation [Tours] (T2i), Institut de Recherche Mathématique de Rennes (IRMAR), Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-École normale supérieure - Rennes (ENS Rennes)-Université de Rennes 2 (UR2)-Centre National de la Recherche Scientifique (CNRS)-INSTITUT AGRO 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), University of Cologne, Eberhard Karls Universität Tübingen = Eberhard Karls University of Tuebingen, Imagerie et cerveau (iBrain - Inserm U1253 - UNIV Tours ), Transgenèse et archivage d'animaux modèles (TAAM), Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physiologie Cellulaire et Moléculaire - UR UPJV 4667 (LPCM), Université de Picardie Jules Verne (UPJV), Institut de Recherche Dupuy de Lôme (IRDL), École Nationale d'Ingénieurs de Brest (ENIB)-Université de Bretagne Sud (UBS)-Université de Brest (UBO)-École Nationale Supérieure de Techniques Avancées Bretagne (ENSTA Bretagne)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Université de Poitiers - Faculté de Médecine et de Pharmacie, Université de Poitiers, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), This project was partly supported by grants on behalf of the following french department committees of Ligue Contre le Cancer Grand-Ouest: 16 (Charente), 37 (Indre-et-Loire), 49 (Maine-et-Loire), 72 (Sarthe) and 85 (Vendée), ANR-11-LABX-0020,LEBESGUE,Centre de Mathématiques Henri Lebesgue : fondements, interactions, applications et Formation(2011), LESUR, Hélène, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), 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), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Pharmacology, Curcumin, [SDV]Life Sciences [q-bio], Calcium signaling, Cell Biology, Colorectal cancer, Sodium-Calcium Exchanger, digestive system diseases, Mitochondria, Mitochondrial Proteins, [SDV] Life Sciences [q-bio], Mice, Cellular and Molecular Neuroscience, Animals, Humans, Molecular Medicine, Calcium, Microsatellite Instability, Colorectal Neoplasms, NCLX, Molecular Biology, Microsatellite Repeats
Abstract: Colorectal cancer (CRC) is associated with high mortality worldwide and new targets are needed to overcome treatment resistance. Recent evidences highlight a role of the mitochondria calcium homeostasis in the development of CRC. In this context, we aimed to evaluate the role of the mitochondrial sodium-calcium-lithium exchanger (NCLX) and its targeting in CRC. We also identified curcumin as a new potential inhibitor of NCLX.In vitro, curcumin exerted strong anti-tumoral activity through its action on NCLX with mtCa2+ and reactive oxygen species overload associated with a mitochondrial membrane depolarization, leading to reduced ATP production and apoptosis through mitochondrial permeability transition pore opening concomitant with G2/M cell cycle arrest. NCLX inhibition with either CGP37157 (a benzodiazepine derivative), small interfering RNA-mediated knock-down or knockout approaches reproduced the effects of curcumin. Altered mitochondrial respiration, cellular aerobic glycolysis and endoplasmic reticulum–mitochondria membrane perturbations participated in these mechanisms. In a xenograft mouse model, NCLX inhibitors decreased CRC tumor growth. Both transcriptomic analysis of The Cancer Genome Atlas dataset and immunohistochemical analysis of tissue microarrays from 381 patients with microsatellite instability (MSI)-driven CRC demonstrated that higher NCLX expression was associated with MSI status and for the first time NCLX expression was significantly associated with recurrence-free survival in MSI CRC patients.Our findings provide strong evidence that blocking NCLX inhibits CRC in vitro and in vivo. We highlight a novel anti-tumoral mechanism of curcumin through its action on NCLX and mitochondria calcium overload that could benefit for therapeutic treatment of patients with MSI CRC.
Published: 2022

6. GC/MS-based 13C metabolic flux analysis resolves the parallel and cyclic photomixotrophic metabolism of Synechocystis sp. PCC 6803 and selected deletion mutants including the Entner-Doudoroff and phosphoketolase pathways

Author: Dennis Schulze, Michael Kohlstedt, Judith Becker, Edern Cahoreau, Lindsay Peyriga, Alexander Makowka, Sarah Hildebrandt, Kirstin Gutekunst, Jean-Charles Portais, Christoph Wittmann, Universität des Saarlandes [Saarbrücken], Toulouse Biotechnology Institute (TBI), 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 Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), MetaToul FluxoMet (TBI-MetaToul), MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-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 Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Toulouse Biotechnology Institute (TBI), 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 Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Geroscience and rejuvenation research center (RESTORE), Université de Toulouse (UT)-Université de Toulouse (UT)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Christian-Albrechts University of Kiel, German Research Foundation (DFG)INST 256/418-1, ANR-11-INBS-0010,METABOHUB,Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation(2011), SCD, INSA Toulouse, Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation - - METABOHUB2011 - ANR-11-INBS-0010 - INBS - VALID, Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-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 Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Toulouse Biotechnology Institute (TBI), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: MESH: Aldehyde-Lyases, MESH: Amino Acids, Calvin-Benson-Bassham cycle, Bioengineering, Glycolytic shunt, Cyanobacteria, Oxidative pentose phosphate pathway, MESH: Carbon Dioxide, 13C metabolic fux analysis, Applied Microbiology and Biotechnology, photomixotrophic growth, Entner-Doudorof pathway, Entner‑Doudoroff pathway, GC–MS, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], TCA cycle, Phosphoketolase pathway, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, NMR, MESH: Gas Chromatography-Mass Spectrometry, Glucose, MESH: Metabolic Flux Analysis, CO2, [SDV.MP.BAC] Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, C metabolic flux analysis, Calvin‑Benson‑Bassham cycle, Biotechnology
Abstract: Background Cyanobacteria receive huge interest as green catalysts. While exploiting energy from sunlight, they co-utilize sugar and CO2. This photomixotrophic mode enables fast growth and high cell densities, opening perspectives for sustainable biomanufacturing. The model cyanobacterium Synechocystis sp. PCC 6803 possesses a complex architecture of glycolytic routes for glucose breakdown that are intertwined with the CO2-fixing Calvin-Benson-Bassham (CBB) cycle. To date, the contribution of these pathways to photomixotrophic metabolism has remained unclear. Results Here, we developed a comprehensive approach for 13C metabolic flux analysis of Synechocystis sp. PCC 6803 during steady state photomixotrophic growth. Under these conditions, the Entner-Doudoroff (ED) and phosphoketolase (PK) pathways were found inactive but the microbe used the phosphoglucoisomerase (PGI) (63.1%) and the oxidative pentose phosphate pathway (OPP) shunts (9.3%) to fuel the CBB cycle. Mutants that lacked the ED pathway, the PK pathway, or phosphofructokinases were not affected in growth under metabolic steady-state. An ED pathway-deficient mutant (Δeda) exhibited an enhanced CBB cycle flux and increased glycogen formation, while the OPP shunt was almost inactive (1.3%). Under fluctuating light, ∆eda showed a growth defect, different to wild type and the other deletion strains. Conclusions The developed approach, based on parallel 13C tracer studies with GC–MS analysis of amino acids, sugars, and sugar derivatives, optionally adding NMR data from amino acids, is valuable to study fluxes in photomixotrophic microbes to detail. In photomixotrophic cells, PGI and OPP form glycolytic shunts that merge at switch points and result in synergistic fueling of the CBB cycle for maximized CO2 fixation. However, redirected fluxes in an ED shunt-deficient mutant and the impossibility to delete this shunt in a GAPDH2 knockout mutant, indicate that either minor fluxes (below the resolution limit of 13C flux analysis) might exist that could provide catalytic amounts of regulatory intermediates or alternatively, that EDA possesses additional so far unknown functions. These ideas require further experiments.
Published: 2022

7. Characterisation of hydrocarbon degradation, biosurfactant production, and biofilm formation in Serratia sp. Tan611: a new strain isolated from industrially contaminated environment in Algeria

Author: Emmanuelle Leize-Wagner, Philippe N. Bertin, Lisa Gil, Frédéric Plewniak, Farid Bensalah, Annela Semai, Céline Lopez-Roques, Céline Vandecasteele, Armelle Charrié-Duhaut, Amalia Sayeh, Génétique moléculaire, génomique, microbiologie (GMGM), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Université d'Oran 1 Ahmed Ben Bella [Oran], Chimie de la matière complexe (CMC), Université de Strasbourg (UNISTRA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Génome et Transcriptome - Plateforme Génomique ( GeT-PlaGe), Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-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-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CNRS national program EC2CO-MicrobiEn: DMO/DMA project, ANR-10-INBS-0009,France-Génomique,Organisation et montée en puissance d'une Infrastructure Nationale de Génomique(2010), Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-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 Toulouse III - Paul Sabatier (UT3)
Subjects: Aromatic hydrocarbon catabolism, Serratia, [SDV.BID]Life Sciences [q-bio]/Biodiversity, Microbiology, Total petroleum hydrocarbons (TPH), 03 medical and health sciences, Bioremediation, Dioxygenase, RNA, Ribosomal, 16S, Food science, Molecular Biology, 030304 developmental biology, chemistry.chemical_classification, 0303 health sciences, biology, Strain (chemistry), 030306 microbiology, Biofilm, Biosurfactant, General Medicine, biology.organism_classification, 16S ribosomal RNA, Hydrocarbons, 6. Clean water, Biodegradation, Environmental, Petroleum, Hydrocarbon, chemistry, 13. Climate action, Algeria, Biofilms, n-alkanes, Bacteria
Abstract: A novel bacterial strain was isolated from industrially contaminated waste water. In the presence of crude oil, this strain was shown to reduce the rate of total petroleum hydrocarbons (TPH) up to 97.10% in 24 h. This bacterium was subsequently identified by 16S rRNA gene sequence analysis and affiliated to the Serratia genus by the RDP classifier. Its genome was sequenced and annotated, and genes coding for catechol 1,2 dioxygenase and naphthalene 1,2-dioxygenase system involved in aromatic hydrocarbon catabolism, and LadA-type monooxygenases involved in alkane degradation, were identified. Gas Chromatography-Mass Spectrometry (GC-MS) analysis of crude oil after biological treatment showed that Serratia sp. Tan611 strain was able to degrade n-alkanes (from C-13 to C-25). This bacterium was also shown to produce a biosurfactant, the emulsification index (E24) reaching 43.47% and 65.22%, against vegetable and crude oil, respectively. Finally, the formation of a biofilm was increased in the presence of crude oil. These observations make Serratia sp. Tan611 a good candidate for hydrocarbon bioremediation.
Published: 2021

8. Environmental and human health issues related to long-term contamination by chlordecone in the French Caribbean

Author: Pierre Benoit, Michel Samson, Guido Rychen, Christophe Mouvet, Jean Pierre Cravedi, Jean-Claude Desenclos, Ecologie fonctionnelle et écotoxicologie des agroécosystèmes (ECOSYS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Bureau de Recherches Géologiques et Minières (BRGM) (BRGM), Unité de Recherches Animal et Fonctionnalités des Produits Animaux (URAFPA), Université de Lorraine (UL)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), 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 ), ANR-16-CE17-0005,GENMSMD,Dissection génétique de la Susceptibilité Mendélienne aux infections mycobactériennes chez l'homme(2016), ANR-16-CE21-0008,INSSICCA,Stratégies innovantes pour sécuriser les systèmes d'élevage dans les zones contaminées par la chlordécone. Une approche modèle développée dans les Antilles et applicable dans les zones contaminées à l'échelle mondiale(2016), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), 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), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA)
Subjects: Insecticides, West Indies, [SDV]Life Sciences [q-bio], Health, Toxicology and Mutagenesis, General Medicine, 010501 environmental sciences, Contamination, 01 natural sciences, Pollution, 3. Good health, Term (time), Human health, Geography, Caribbean Region, Chlordecone, Environmental health, Humans, Environmental Chemistry, Ecotoxicology, ComputingMilieux_MISCELLANEOUS, 0105 earth and related environmental sciences
Abstract: International audience
Published: 2020

9. Inhibition of ubiquitin-specific protease 7 sensitizes acute myeloid leukemia to chemotherapy

Author: Pierre-Luc Mouchel, Laure David, Jean-Emmanuel Sarry, Véronique Mansat-De Mas, Sarah Bertoli, Maëlle Cartel, Mathilde Gotanègre, Stéphane Manenti, Arnaud Besson, Christine Didier, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Équipe labellisée Ligue Nationale Contre le Cancer [Toulouse], Ligue Nationale Contre le Cancer [Paris] (LNCC), Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche en Santé Digestive (IRSD ), 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-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération (LBCMCP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Ligue nationale contre le cancer, SEGUIN, Nathalie, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, 0301 basic medicine, Cancer Research, medicine.medical_treatment, Apoptosis, Mice, SCID, Ubiquitin-Specific Peptidase 7, Transcriptome, Mice, 0302 clinical medicine, Mice, Inbred NOD, hemic and lymphatic diseases, Tumor Cells, Cultured, RNA, Small Interfering, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Cytarabine, Myeloid leukemia, Hematology, Middle Aged, Prognosis, 3. Good health, Gene Expression Regulation, Neoplastic, Survival Rate, Leukemia, Myeloid, Acute, Oncology, 030220 oncology & carcinogenesis, Female, Signal Transduction, Cell signalling, medicine.drug, Antimetabolites, Antineoplastic, Programmed cell death, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, Acute myeloid leukaemia, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Biomarkers, Tumor, medicine, Animals, Humans, Cell Proliferation, Chemotherapy, business.industry, Cell growth, Gene Expression Profiling, Gene signature, Xenograft Model Antitumor Assays, 030104 developmental biology, Drug Resistance, Neoplasm, Cell culture, Cancer research, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; Resistance of acute myeloid leukemia (AML) to therapeutic agents is frequent. Consequently, the mechanisms leading tothis resistance must be understood and addressed. In this paper, we demonstrate that inhibition of deubiquitinylaseUSP7 significantly reduces cell proliferation in vitro and in vivo, blocks DNA replication progression and increases celldeath in AML. Transcriptomic dataset analyses reveal that a USP7 gene signature is highly enriched in cells from AMLpatients at relapse, as well as in residual blasts from patient-derived xenograft (PDX) models treated with clinically relevantdoses of cytarabine, which indicates a relationship between USP7 expression and resistance to therapy. Accordingly, singlecellanalysis of AML patient samples at relapse versus at diagnosis showed that a gene signature of the pre-existingsubpopulation responsible for relapse is enriched in transcriptomes of patients with a high USP7 level. Furthermore, wefound that USP7 interacts and modulates CHK1 protein levels and functions in AML. Finally, we demonstrated that USP7inhibition acts in synergy with cytarabine to kill AML cell lines and primary cells of patients with high USP7 levels.Altogether, these data demonstrate that USP7 is both a marker of resistance to chemotherapy and a potential therapeutictarget in overcoming resistance to treatment.
Published: 2020

10. House dust mites activate nociceptor–mast cell clusters to drive type 2 skin inflammation

Author: Mindy Tsai, Camille Petitfils, Nicolas Cenac, Stephen J. Galli, Riccardo Sibilano, Xinzhong Dong, Laurent L. Reber, Nicolas Gaudenzio, Lilian Basso, Philipp Starkl, Nadine Serhan, Chrystelle Bonnart, Thomas Marichal, James Meixiong, Institut National de la Santé et de la Recherche Médicale (INSERM), Stanford University School of Medicine [CA, USA], Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Johns Hopkins University, School of Medicine, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Liège, Walloon Excellence in Life sciences and BIOtechnology [Liège] (WELBIO), Research Center for Molecular Medicine of the Austrian Academy of Sciences, Medizinische Universität Wien = Medical University of Vienna, the Stanford Neuroscience Microscopy Service (supported by NIH No. NS069375), (IFR30, Plateau Technique Cytometrie, Toulouse), (IFR30, Plateau Technique Imagerie Cellulaire, Toulouse), ‘Incentive Grant for Scientific Research’ of the F.R.S.-FNRS (No. F.4508.18), by the FRFS-WELBIO under grant No. CR-2017 s-04, by the Acteria Foundation and by an ERC Starting Grant (No. IM-ID 801823), the Austrian Science Fund (No. P31113-B30), ProdInra, Migration, Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT)
Subjects: Male, 0301 basic medicine, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, MESH: Nociceptors / metabolism, Dermatitis, MESH: Skin / cytology, Cell Communication, MESH: Mast Cells / metabolism, MESH: Tachykinins / genetics, MESH: Dermatitis, Atopic / pathology, MESH: Mice, Knockout, Receptors, G-Protein-Coupled, Mice, 0302 clinical medicine, TAC1, Receptors, 2.1 Biological and endogenous factors, Immunology and Allergy, Mast Cells, Aetiology, Acute inflammation, Skin, Mice, Knockout, MESH: Cell Communication / immunology, Chemistry, MESH: Dermatitis, Atopic / immunology, Pyroglyphidae, Pain Research, Degranulation, Nociceptors, Mast cell, Research Highlight, MESH: Mast Cells / immunology, 3. Good health, Nociception, medicine.anatomical_structure, Nociceptor, MESH: Tachykinins / metabolism, Female, Chronic Pain, medicine.symptom, Cell signalling, MESH: Skin / immunology, Knockout, Immunology, TRPV1, TRPV Cation Channels, Inflammation, MESH: Nociceptors / immunology, Article, Atopic, Dermatitis, Atopic, G-Protein-Coupled, 03 medical and health sciences, Tachykinins, medicine, Animals, Humans, MESH: Receptors, G-Protein-Coupled / metabolism, Animal, Inflammatory and immune system, Neurosciences, MESH: Allergens / immunology, MESH: TRPV Cation Channels / metabolism, MESH: Pyroglyphidae / immunology, Allergens, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, Disease Models, Animal, 030104 developmental biology, nervous system, Disease Models, Itching, MESH: Disease Models, Animal, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, 030215 immunology
Abstract: International audience; Allergic skin diseases, such as atopic dermatitis, are clinically characterized by severe itching and type 2 immunity-associated hypersensitivity to widely distributed allergens, including those derived from house dust mites (HDMs). Here we found that HDMs with cysteine protease activity directly activated peptidergic nociceptors, which are neuropeptide-producing nociceptive sensory neurons that express the ion channel TRPV1 and Tac1, the gene encoding the precursor for the neuropeptide substance P. Intravital imaging and genetic approaches indicated that HDM-activated nociceptors drive the development of allergic skin inflammation by inducing the degranulation of mast cells contiguous to such nociceptors, through the release of substance P and the activation of the cationic molecule receptor MRGPRB2 on mast cells. These data indicate that, after exposure to HDM allergens, activation of TRPV1+Tac1+ nociceptor–MRGPRB2+ mast cell sensory clusters represents a key early event in the development of allergic skin reactions.
Published: 2019

11. Osmolality-based normalization enhances statistical discrimination of untargeted metabolomic urine analysis: results from a comparative study

Author: Marie Tremblay-Franco, Pilar Galan, Loïc Mervant, Emmanuelle Kesse-Guyot, Jean-François Martin, Françoise Guéraud, Emilien L. Jamin, Laurent Debrauwer, Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-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)-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-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), 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)-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), 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), Prévention et promotion de la cancérogénèse par les aliments (ToxAlim-PPCA), ToxAlim (ToxAlim), 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), The BioNutriNet project was supported by the French National Research Agency (Agence Nationale de la Recherche) in the context of the 2013 Programme de Recherche Systemes Alimentaires Durables (ANR-13-ALID-0001), ANR-13-ALID-0001,BioNutriNet,Consommation d'aliments issus de l'agriculture biologique: déterminants et motivation vis-à-vis de la durabilité, impact nutritionnel, économique, environnemental et toxicologique(2013), Université Fédérale Toulouse Midi-Pyrénées-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 Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), LESUR, Hélène, Systèmes Alimentaires Durables - Consommation d'aliments issus de l'agriculture biologique: déterminants et motivation vis-à-vis de la durabilité, impact nutritionnel, économique, environnemental et toxicologique - - BioNutriNet2013 - ANR-13-ALID-0001 - ALID - VALID, Metatoul AXIOM (E20 ), MetaboHUB-MetaToul, 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), and 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)
Subjects: Normalization (statistics), [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Osmolality, Urine analysis, Urine, Urinalysis, 01 natural sciences, Biochemistry, 03 medical and health sciences, Metabolomics, Statistics, Humans, Trial registration, 030304 developmental biology, Mathematics, 0303 health sciences, Mass spectrometry, Untargeted metabolomics, Osmolar Concentration, 010401 analytical chemistry, Confounding, Liquid Biopsy, Statistical model, Body Fluids, 0104 chemical sciences, [SDV] Life Sciences [q-bio], [SDV.TOX] Life Sciences [q-bio]/Toxicology, Normalization, Data Interpretation, Statistical, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Metabolome, Statistical discrimination, Chromatography, Liquid
Abstract: International audience; Introduction: Because of its ease of collection, urine is one of the most commonly used matrices for metabolomics studies. However, unlike other biofluids, urine exhibits tremendous variability that can introduce confounding inconsistency during result interpretation. Despite many existing techniques to normalize urine samples, there is still no consensus on either which method is most appropriate or how to evaluate these methods.Objectives: To investigate the impact of several methods and combinations of methods conventionally used in urine metabolomics on the statistical discrimination of two groups in a simple metabolomics study.Methods: We applied 14 different strategies of normalization to forty urine samples analysed by liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS). To evaluate the impact of these different strategies, we relied on the ability of each method to reduce confounding variability while retaining variability of interest, as well as the predictability of statistical models.Results: Among all tested normalization methods, osmolality-based normalization gave the best results. Moreover, we demonstrated that normalization using a specific dilution prior to the analysis outperformed post-acquisition normalization. We also demonstrated that the combination of various normalization methods does not necessarily improve statistical discrimination.Conclusions: This study re-emphasized the importance of normalizing urine samples for metabolomics studies. In addition, it appeared that the choice of method had a significant impact on result quality. Consequently, we suggest osmolality-based normalization as the best method for normalizing urine samples.
Published: 2021

12. Development of a set of SNP markers for population genetics of the red gorgonian (Paramuricea clavata), an emblematic species of the Mediterranean coralligenous

Author: M. Padrón, M. Massot, E. Guichoux, M. Milhes, Laboratoire d'Ecogéochimie des environnements benthiques (LECOB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Observatoire océanologique de Banyuls (OOB), Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Génome et Transcriptome - Plateforme Génomique ( GeT-PlaGe), Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-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-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biodiversité, Gènes & Communautés (BioGeCo), Université de Bordeaux (UB)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), ANR-10-EQPX-0016,XYLOFOREST,Plateforme d'Innovation ' Forêt-Bois-Fibre-Biomasse du Futur '(2010), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-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 Toulouse III - Paul Sabatier (UT3), and EC Interreg Marittimo program under Project IMPACT - IMpatto Portuale su aree marine protette: Azioni Cooperative TransfrontaliereCUP B12F17000370005
Subjects: 0106 biological sciences, 0301 basic medicine, Mediterranean climate, MassARRAY, ved/biology.organism_classification_rank.species, [SDU.STU]Sciences of the Universe [physics]/Earth Sciences, Population genetics, Paramuricea clavata, Single-nucleotide polymorphism, Biology, 010603 evolutionary biology, 01 natural sciences, 03 medical and health sciences, Snp markers, Genetics, SNP, Ecology, Evolution, Behavior and Systematics, ved/biology, biology.organism_classification, Single nucleotide polymorphism, Phylogeography, 030104 developmental biology, Gorgonian, Evolutionary biology, [SDE]Environmental Sciences
Abstract: International audience; Transcriptome sequencing was used for the development of single nucleotide polymorphisms (SNP) for the red gorgonian (Paramuricea clavata). A total of 20,736 SNPs were identified, and 1718 had a coverage of over 100 reads. Of the 480 SNPs tested, 347 SNPs were successfully genotyped at 95 samples from the NW Mediterranean using a MassARRAY System. This set of markers will be of great value for population genetics and phylogeography.
Published: 2020

13. Genetic architecture of a plant adaptive trait: QTL mapping of intraspecific variation for tolerance to metal pollution in Arabidopsis halleri

Author: Olivier Bouchez, Dima Souleman, Charles Poncet, Sophie Gallina, Hélène Frérot, Julien Spielmann, Marie-Joe Karam, Marc Hanikenne, M. Sol Schvartzman, Maxime Pauwels, Université de Lille, Université de Liège, Génétique Diversité et Ecophysiologie des Céréales (GDEC), Institut National de la Recherche Agronomique (INRA)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), Génome et Transcriptome - Plateforme Génomique (GeT-PlaGe), Institut National de la Recherche Agronomique (INRA)-Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-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 Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), French National Research Agency (ANR ELOCANTH) ANR-12-JSV7-0010 / Fonds de la Recherche Scientifique-FNRS PDR-T.0206.13 / University of Liege SFRD-12/03, Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Université Fédérale Toulouse Midi-Pyrénées-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 Toulouse III - Paul Sabatier (UT3)
Subjects: 0106 biological sciences, 0301 basic medicine, [SDV.OT]Life Sciences [q-bio]/Other [q-bio.OT], Candidate gene, Genotype, Quantitative Trait Loci, Arabidopsis, Sequence assembly, Context (language use), adaptation, Quantitative trait locus, Biology, 010603 evolutionary biology, 01 natural sciences, Genome, Article, Intraspecific competition, 03 medical and health sciences, Species Specificity, evolution, Genetics, mobilization, Genetics (clinical), Human evolutionary genetics, zinc, cadmium tolerance, Chromosome Mapping, 15. Life on land, Adaptation, Physiological, Genetic architecture, 030104 developmental biology, Metals, metallicolou population, Evolutionary biology
Abstract: International audience; Anthropogenic activities are among the main drivers of global change and result in drastic habitat modifications, which represent strong evolutionary challenges for biological species that can either migrate, adapt, or disappear. In this context, understanding the genetics of adaptive traits is a prerequisite to enable long-term maintenance of populations under strong environmental constraints. To examine these processes, a QTL approach was developed here using the pseudometallophyte Arabidopsis halleri, which displays among-population adaptive divergence for tolerance to metallic pollution in soils. An F2 progeny was obtained by crossing individuals from metallicolous and non-metallicolous populations from Italian Alps, where intense metallurgic activities have created strong landscape heterogeneity. Then, we combined genome de novo assembly and genome resequencing of parental genotypes to obtain single-nucleotide polymorphism markers and achieve high-throughput genotyping of the progeny. QTL analysis was performed using growth parameters and photosynthetic yield to assess zinc tolerance levels. One major QTL was identified for photosynthetic yield. It explained about 27% of the phenotypic variance. Functional annotation of the QTL and gene expression analyses highlighted putative candidate genes. Our study represents a successful approach combining evolutionary genetics and advanced molecular tools, helping to better understand how a species can face new selective pressures of anthropogenic origin.
Published: 2019

14. Deepoxy-deoxynivalenol retains some immune-modulatory properties of the parent molecule deoxynivalenol in piglets

Author: Ana Paula Frederico Rodrigues Loureiro Bracarense, Alix Pierron, Joëlle Laffitte, Gerd Schatzmayr, Philippe Pinton, Isabelle P. Oswald, Wulf-Dieter Moll, H.E. Schwartz-Zimmermann, Anne-Marie Cossalter, Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), 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-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), BIOMIN Research Center, Lab. Patologia Animal, State University of Londrina = Universidade Estadual de Londrina, Plateforme Ezop (Ezop), University of Natural Ressources and Life Science, A. Pierron was supported by fellowship from CIFRE (2012/0572, jointly financed by the BIOMIN Holding GmbH, Association Nationale de la Recherche Technique and INRA), Biomin Research Center, Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées
Subjects: pig, Male, 0301 basic medicine, epoxy group, Swine, Health, Toxicology and Mutagenesis, Trichothecene, [SDV.TOX.TVM]Life Sciences [q-bio]/Toxicology/Vegetal toxicology and mycotoxicology, Ileum, [SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain, Pharmacology, Biology, Weight Gain, Toxicology, medicine.disease_cause, immune response, Jejunum, 03 medical and health sciences, 0404 agricultural biotechnology, Immune system, In vivo, Intestine, Small, medicine, Animals, modified mycotoxins, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Toxin, epoxy-group, 04 agricultural and veterinary sciences, General Medicine, 040401 food science, 3. Good health, in vivo, Ovalbumin, 030104 developmental biology, medicine.anatomical_structure, Liver, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Immune System, Toxicity, biology.protein, Trichothecenes
Abstract: International audience; Deoxynivalenol (DON) is the most abundant trichothecene in food and feed. It causes both acute and chronic disorders of the human and animal intestine, liver and the immune system. The structural basis for the toxicity of DON has not been fully elucidated. Using the pig as a target and a model species for human, the toxicity of DON and its deepoxy-metabolite (DOM-1) were compared. Animals were exposed by gavage to 1 and 0.5 nmol toxin/kg bw./day for two and three weeks respectively. Whatever the dose/duration, DOM-1 was less toxic than DON in terms of weight gain and emesis. In the three week experiment, animals were vaccinated with ovalbumin, and their immune response was analyzed in addition to tissue morphology, biochemistry and hematology. DON impaired the morphology of the jejunum and the ileum, reduced villi height, decreased Ecadherin expression and modified the intestinal expression of cytokine. Similarly, DON induced hepatotoxicity as indicated by the lesion score and the blood biochemistry. By contrast, DOM-1 only induced minimal intestinal toxicity and did not trigger hepatotoxicity. As far as the immune response was concerned, the effects of ingesting DOM-1 were similar to those caused by DON, as measured by histopathology of lymphoid organs, PCNA expression and the specific antibody responses. Taken together, these data demonstrated that DOM-1, a microbial detoxification product of DON, was not toxic in the sensitive pig model but retained some immunemodulatory properties of DON, especially its ability to stimulate a specific antibody response during a vaccination protocol.
Published: 2018

15. Priming for welfare: gut microbiota is associated with equitation conditions and behavior in horse athletes

Author: Núria Mach, Aline Foury, Samuel Pennarun, Allison Clark, Sophie Dhorne-Pollet, Yuliaxis Ramayo-Caldas, Léa Lansade, Alice Ruet, Elisa Crisci, Marie-Pierre Moisan, David Bars-Cortina, Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Physiologie de la reproduction et des comportements [Nouzilly] (PRC), Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Vall Hebron Research Institute (VHIR), Institute of Agrifood Research and Technology (IRTA), Génétique Animale et Biologie Intégrative (GABI), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Génome et Transcriptome - Plateforme Génomique (GeT-PlaGe), Institut National de la Recherche Agronomique (INRA)-Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), 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-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 Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Nutrition et Neurobiologie intégrée (NutriNeuro), Université de Bordeaux (UB)-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), European Project: 6655919,P-Sphere, Institut Français du Cheval et de l'Equitation [Saumur]-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Paris-Saclay-AgroParisTech-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Producció Animal, Genètica i Millora Animal, Institut Français du Cheval et de l'Equitation [Saumur] (IFCE)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Recerca i Tecnologia Agroalimentàries = Institute of Agrifood Research and Technology (IRTA), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-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 Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), and Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Male, Health Status, [SDV]Life Sciences [q-bio], media_common.quotation_subject, lcsh:Medicine, Zoology, Environment, Gut flora, Microbiology, digestive system, Article, Behavioural methods, Cohort Studies, Feces, 03 medical and health sciences, fluids and secretions, 0302 clinical medicine, Physical Conditioning, Animal, medicine, Animals, Elite athletes, Horses, lcsh:Science, 030304 developmental biology, media_common, 0303 health sciences, Multidisciplinary, Behavior, Animal, biology, Athletes, lcsh:R, Stressor, Horse, Biodiversity, Hypervigilance, biology.organism_classification, Gastrointestinal Microbiome, Phenotype, lcsh:Q, Female, medicine.symptom, Systems biology, Welfare, Priming (psychology), 030217 neurology & neurosurgery, Neuroscience, Sports
Abstract: We simultaneously measured the fecal microbiota and multiple environmental and host-related variables in a cohort of 185 healthy horses reared in similar conditions during a period of eight months. The pattern of rare bacteria varied from host to host and was largely different between two time points. Among a suite of variables examined, equitation factors were highly associated with the gut microbiota variability, evoking a relationship between gut microbiota and high levels of physical and mental stressors. Behavioral indicators that pointed toward a compromised welfare state (e.g. stereotypies, hypervigilance and aggressiveness) were also associated with the gut microbiota, reinforcing the notion for the existence of the microbiota-gut-brain axis. These observations were consistent with the microbiability of behaviour traits (> 15%), illustrating the importance of gut microbial composition to animal behaviour. As more elite athletes suffer from stress, targeting the microbiota offers a new opportunity to investigate the bidirectional interactions within the brain gut microbiota axis.
Published: 2020

16. Author Correction: Dimorphic metabolic and endocrine disorders in mice lacking the constitutive androstane receptor

Author: Marion Régnier, Vassilia Theodorou, Hervé Guillou, Yannick Lippi, Frédéric Lasserre, Sarra Smati, Françoise Lenfant, Laurence Guzylack-Pirou, Claire Naylies, Arnaud Polizzi, Nicolas Loiseau, Céline Lukowicz, Sandrine Ménard, Sharon Barretto, Frédéric Boudou, Pierre Gourdy, Fabiana Oliviero, Justine Bertrand-Michel, Laila Mselli-Lakhal, Anne Fougerat, Alexandra Montagner, Sandrine Ellero-Simatos, Afifa Ait Belgnaoui, Laurence Gamet-Payrastre, Nicola Marchi, 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), Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), 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), Exposition, Perturbation Endocrino-métabolique et Reproduction (ToxAlim-EXPER), Institut National de la Santé et de la Recherche Médicale (INSERM), Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), Transcriptomic impact of Xenobiotics (E23 TRiX), Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), 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), MetaboHUB, Centre National de la Recherche Scientifique (CNRS), Université Fédérale Toulouse Midi-Pyrénées-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 Toulouse III - Paul Sabatier (UT3), and ProdInra, Migration
Subjects: 0303 health sciences, medicine.medical_specialty, Multidisciplinary, lcsh:R, lcsh:Medicine, Biology, 3. Good health, [SDV.TOX] Life Sciences [q-bio]/Toxicology, Sexual dimorphism, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, 03 medical and health sciences, 0302 clinical medicine, Endocrinology, [SDV.TOX]Life Sciences [q-bio]/Toxicology, 030220 oncology & carcinogenesis, Internal medicine, Constitutive androstane receptor, medicine, Endocrine system, lcsh:Q, lcsh:Science, Author Correction, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology
Abstract: Metabolic diseases such as obesity, type II diabetes and hepatic steatosis are a public health concern in developed countries. The metabolic risk is gender-dependent. The constitutive androstane receptor (CAR), which is at the crossroads between energy metabolism and endocrinology, has recently emerged as a promising therapeutic agent for the treatment of obesity and type 2 diabetes. In this study we sought to determine its role in the dimorphic regulation of energy homeostasis. We tracked male and female WT and CAR deficient (CAR-/-) mice for over a year. During aging, CAR-/- male mice developed hypercortisism, obesity, glucose intolerance, insulin insensitivity, dyslipidemia and hepatic steatosis. Remarkably, the latter modifications were absent, or minor, in female CAR-/- mice. When ovariectomized, CAR-/- female mice developed identical patterns of metabolic disorders as observed in male mice. These results highlight the importance of steroid hormones in the regulation of energy metabolism by CAR. They unveil a sexually dimorphic role of CAR in the maintenance of endocrine and metabolic homeostasis underscoring the importance of considering sex in treatment of metabolic diseases.
Published: 2020

17. Longitudinal analysis of the salivary metabolome of breast-fed and formula-fed infants over the first year of life

Author: Cécile Canlet, Camille Schwartz, Eric Neyraud, Marie Tremblay-Franco, Carole Tournier, Isabelle Jouanin, Hélène Brignot, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), 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-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 Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), 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)-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), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-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)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), and Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-ToxAlim (ToxAlim)
Subjects: Saliva, Time Factors, Proton Magnetic Resonance Spectroscopy, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Tooth eruption, Breastfeeding, Physiology, First year of life, Oral cavity, 01 natural sciences, Biochemistry, 03 medical and health sciences, Metabolome, Humans, Metabolomics, Medicine, Longitudinal Studies, 030304 developmental biology, 0303 health sciences, business.industry, 010401 analytical chemistry, Infant, Infant Formula, NMR, 0104 chemical sciences, Breast Feeding, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, Formula fed, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Introduction The salivary metabolome has been increasingly studied over the past ten years due to the potential of saliva as a non-invasive source of biomarkers. However, although saliva has been studied in relation to various diseases, its dynamic evolution during life is not known. This is particularly true for the first months of life. Infancy is indeed a critical period during which numerous behavioural and physiological events occur, such as dietary transitions and tooth eruption, which can lead to important biological modifications in the oral cavity. Objectives The aim of this work was therefore to study the evolution of the salivary metabolome during the first months of life by H-1 NMR. Methods Saliva of 32 infants with different milk feeding histories (breast vs formula) was collected at 6 stages, including 3 months old, 15 days before the onset of complementary feeding (CF), approximately 15 days after the onset of CF, approximately 21 days after the onset of CF and at approximately 11 and 15 months, and analysed. Results The longitudinal analysis showed a significant modification of the profiles of 18 metabolites over time; 14 presented an increase in abundance whereas 4 presented a decrease. These modifications seemed to be linked, for the most part, to an increase in oral microbial metabolism. Milk feeding history during the first months of life had no effect on metabolites. Conclusion This work shows that the salivary metabolome should be considered when studying the changes occurring during infancy.
Published: 2020

18. Structure of the intergenic spacers in chicken ribosomal DNA

Author: Svetlana Galkina, Anastasia Sokolovskaya, Elena Gaginskaya, Nathalie Rodde, Stéphane Cauet, Céline Lopez-Roques, Alsu Saifitdinova, Christophe Klopp, Alexander Dyomin, Valerie Fillon, Alain Vignal, Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centre National de Ressources Génomiques Végétales (CNRGV), Institut National de la Recherche Agronomique (INRA), Génome et Transcriptome - Plateforme Génomique (GeT-PlaGe), Institut National de la Recherche Agronomique (INRA)-Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-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 Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Système d'Information des GENomes des Animaux d'Elevage (SIGENAE), Russian Foundation for Basic Research (RFBR) 18-04-01276A / Saint Petersburg State University's Programme 4 1.40.1625.2017, Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), and INRA (GeT-PlaGE)
Subjects: lcsh:QH426-470, chicken, [SDV]Life Sciences [q-bio], dna, Biology, DNA, Ribosomal, Genome, genomic, 03 medical and health sciences, Intergenic region, Tandem repeat, Sequence Homology, Nucleic Acid, DNA, Ribosomal Spacer, Gene cluster, Genetics, Animals, Ribosomal DNA, Gene, Conserved Sequence, Ecology, Evolution, Behavior and Systematics, lcsh:SF1-1100, 030304 developmental biology, 2. Zero hunger, 0303 health sciences, Contig, 030302 biochemistry & molecular biology, General Medicine, Ribosomal RNA, lcsh:Genetics, Animal Science and Zoology, lcsh:Animal culture, genetic, Chickens, Research Article, Autre (Sciences du Vivant)
Abstract: Background Ribosomal DNA (rDNA) repeats are situated in the nucleolus organizer regions (NOR) of chromosomes and transcribed into rRNA for ribosome biogenesis. Thus, they are an essential component of eukaryotic genomes. rDNA repeat units consist of rRNA gene clusters that are transcribed into single pre-rRNA molecules, each separated by intergenic spacers (IGS) that contain regulatory elements for rRNA gene cluster transcription. Because of their high repeat content, rDNA sequences are usually absent from genome assemblies. In this work, we used the long-read sequencing technology to describe the chicken IGS and fill the knowledge gap on rDNA sequences of one of the key domesticated animals. Methods We used the long-read PacBio RSII technique to sequence the BAC clone WAG137G04 (Wageningen BAC library) known to contain chicken NOR elements and the HGAP workflow software suit to assemble the PacBio RSII reads. Whole-genome sequence contigs homologous to the chicken rDNA repetitive unit were identified based on the Gallus_gallus-5.0 assembly with BLAST. We used the Geneious 9.0.5 and Mega software, maximum likelihood method and Chickspress project for sequence evolution analysis, phylogenetic tree construction and analysis of the raw transcriptome data. Results Three complete IGS sequences in the White Leghorn chicken genome and one IGS sequence in the red junglefowl contig AADN04001305.1 (Gallus_gallus-5.0) were detected. They had various lengths and contained three groups of tandem repeats (some of them being very GC rich) that form highly organized arrays. Initiation and termination sites of rDNA transcription were located within small and large unique regions (SUR and LUR), respectively. No functionally significant sites were detected within the tandem repeat sequences. Conclusions Due to the highly organized GC-rich repeats, the structure of the chicken IGS differs from that of IGS in human, apes, Xenopus or fish rDNA. However, the chicken IGS shares some molecular organization features with that of the turtles, which are other representatives of the Sauropsida clade that includes birds and reptiles. Our current results on the structure of chicken IGS together with the previously reported ribosomal gene cluster sequence provide sufficient data to consider that the complete chicken rDNA sequence is assembled with confidence in terms of molecular DNA organization.
Published: 2019

19. Saturated, mono- and polyunsaturated fatty acid intake and cancer risk: results from the French prospective cohort NutriNet-Santé

Author: Françoise Guéraud, Mélanie Deschasaux, Fabrice Pierre, Céline Lavalette, Mathilde Touvier, Emmanuelle Kesse-Guyot, Bernard Srour, Laury Sellem, Serge Hercberg, Pilar Galan, Paule Latino-Martel, Manon Egnell, Philippine Fassier, Thibault Fiolet, Equipe 3: EREN- Equipe de Recherche en Epidémiologie Nutritionnelle (CRESS - U1153), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), 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)-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), Prévention et promotion de la cancérogénèse par les aliments (ToxAlim-PPCA), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), 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-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Ministere de la Sante, Institut de Veille Sanitaire (InVS), Institut National de la Prevention et de l'Education pour la Sante (INPES), Region Ile-de-France (CORDDIM), Institut National de la Sante et de la Recherche Medicale (INSERM), Institut National de la Recherche Agronomique (INRA), Conservatoire National des Arts et Metiers (CNAM), Universite Paris 13, Canceropole Ile de France/Region Ile de France, French National Cancer Institute [INCa_8085], Srour, Bernard, Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-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)-Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, and 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 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)
Subjects: Male, 0301 basic medicine, [SDV]Life Sciences [q-bio], medicine.medical_treatment, Medicine (miscellaneous), Physiology, Ascorbic Acid, Antioxidants, Cohort Studies, Cancer risk, 0302 clinical medicine, Neoplasms, Vegetables, Vitamin E, Prospective Studies, Prospective cohort study, 2. Zero hunger, chemistry.chemical_classification, Nutrition and Dietetics, food and beverages, Vitamins, Middle Aged, Lipids, Eicosapentaenoic acid, Diet Records, 3. Good health, [SDV] Life Sciences [q-bio], Docosahexaenoic acid, Female, France, Polyunsaturated fatty acid, 030209 endocrinology & metabolism, Risk Assessment, 03 medical and health sciences, Breast cancer, Dietary Fats, Unsaturated, medicine, Humans, Saturated fatty acids, Proportional Hazards Models, 030109 nutrition & dietetics, Vitamin C, business.industry, Cancer, Prospective cohort, medicine.disease, Dietary Fats, Diet, chemistry, Fruit, PUFAs, business
Abstract: International audience; Lipid intakes such as saturated (SFA), monounsaturated (MUFA) and polyunsaturated (PUFA) fatty acids have been widely studied regarding cardiovascular health, but their relevance to cancer is unclear. Inconsistent epidemiological results may be explained by varied mechanisms involving PUFAs and redox balance, inflammatory status and cell signalling, along with interactions with other dietary components such as antioxidants, dietary fibre and more generally fruits and vegetable intakes. Therefore, this study aimed to investigate the associations between lipid intakes and cancer risk, and their potential modulation by vitamin C, vitamin E, dietary fibre and fruit and vegetable intakes.METHODS:This prospective study included 44,039 participants aged ≥ 45 years from the NutriNet-Santé cohort (2009-2017). Dietary data were collected using repeated 24 h-dietary records. Multivariable Cox models were performed to characterize associations.RESULTS:SFA intake was associated with increased overall [n = 1722 cases, HRQ5vsQ1 = 1.44 (1.10-1.87), p-trend = 0.008] and breast [n = 545 cases, HRQ5vsQ1 = 1.98 (1.24-3.17), p-trend = 0.01] cancer risks. n-6 PUFA [HRQ5vsQ1 = 0.56 (0.32-0.97), p-trend = 0.01] and MUFA (HRQ5vsQ1 = 0.41 [0.18-0.0.95), p-trend = 0.009] intakes were associated with a decreased risk of digestive cancers (n = 190 cases). Associations between n-6 PUFA, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intakes and digestive cancer risk were modulated by dietary fibre, vitamin C and fruit and vegetable intakes.CONCLUSION:These findings suggested that SFA intake could increase overall and breast cancer risks while some unsaturated fatty acids could decrease digestive cancer risk. However, in line with mechanistic hypotheses, our results suggest that intakes of fruits and vegetables and their constituents (antioxidants, fibre) may interact with PUFAs to modulate these associations.
Published: 2018

20. T-lymphocyte-derived enkephalins reduce Th1/Th17 colitis and associated pain in mice

Author: Nicolas Cenac, Jérôme Boué, Sophie Laffont, Arnaud Bessac, Gilles Dietrich, Laure Garnier, Lilian Basso, Catherine Blanpied, Institut de Recherche en Santé Digestive (IRSD ), Institut National de la Recherche Agronomique (INRA)-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-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT)
Subjects: 0301 basic medicine, enkephalin, Enkephalin, medicine.drug_class, T lymphocytes, Intestinal inflammation, Inflammation, enképhaline, (+)-Naloxone, lymphocyte, 03 medical and health sciences, 0302 clinical medicine, Opioid receptor, inflammation intestinale, Medicine, pain, Colitis, T-lymphocytes, Endogenous opioid, business.industry, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Visceral pain, Enkephalins, medicine.disease, 3. Good health, 030104 developmental biology, Opioid, Immunology, douleur, medicine.symptom, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: BACKGROUND:Endogenous opioids, including enkephalins, are fundamental regulators of pain. In inflammatory conditions, the local release of opioids by leukocytes at the inflammatory site inhibits nociceptor firing, thereby inducing analgesia. Accordingly, in chronic intestinal Th1/Th17-associated inflammation, enkephalins released by colitogenic CD4+ T lymphocytes relieve inflammation-induced visceral pain. The present study aims to investigate whether mucosal T-cell-derived enkephalins also exhibit a potent anti-inflammatory activity as described for exogenous opioid drugs in Th1/Th17-associated colitis.METHODS:The anti-inflammatory effects of endogenous opioids were investigated in both Th1/Th17-associated (transfer of CD4+CD45RBhigh T lymphocytes) and Th2-associated (oxazolone) colitis models in mice. Inflammation-induced colonic damage and CD4+ T cell subsets were compared in mice treated or not treated with naloxone methiodide, a peripheral antagonist of opioid receptors. The anti-inflammatory activity of T-cell-derived enkephalins was further estimated by comparison of colitis severity in immunodeficient mice into which naïve CD4+CD45RBhigh T lymphocytes originating from wild-type or enkephalin-knockout mice had been transferred.RESULTS:Peripheral opioid receptor blockade increases the severity of Th1/Th17-induced colitis and attenuates Th2 oxazolone colitis. The opposite effects of naloxone methiodide treatment in these two models of intestinal inflammation are dependent on the potency of endogenous opioids to promote a Th2-type immune response. Accordingly, the transfer of enkephalin-deficient CD4+CD45RBhigh T lymphocytes into immunodeficient mice exacerbates inflammation-induced colonic injury.CONCLUSIONS:Endogenous opioids, including T-cell-derived enkephalins, promote a Th2-type immune response, which, depending on the context, may either attenuate (Th1/Th17-associated) or aggravate (Th2-associated) intestinal inflammation.
Published: 2017

21. Patulin transformation products and last intermediates in its biosynthetic pathway, E- and Z-ascladiol, are not toxic to human cells

Author: Joanna Tannous, Isabelle P. Oswald, Thierry Gauthier, Rhoda El Khoury, Cécile Canlet, Philippe Pinton, Selma P. Snini, Ali Atoui, André El Khoury, Ting Zhou, Roger Lteif, Yannick Lippi, Olivier Puel, Imourana Alassane-Kpembi, ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-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, Faculté des Sciences, Centre d’Analyses et de Recherches, Université Saint-Joseph de Beyrouth (USJ), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-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 Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), Transcriptomic impact of Xenobiotics (E23 TRiX), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Plateforme Génome & Transcriptome (GET), Contaminants & Stress Cellulaire (ToxAlim-COMICS), Lebanese Atomic Energy Commission, Centre National de la Recherche Scientifique (CNRS), Faculty of Sciences, Laboratory of Microbiology, Department of Biology, Lebanese University [Beirut] (LU), Guelph Research and Development Center, Agriculture and Agri-Food [Ottawa] (AAFC), project CASDAR AAP RT 2015 No. 1523, Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-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 la Recherche Agronomique (INRA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-MetaToul-MetaboHUB, Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-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 Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Plateforme Génome & Transcriptome (GET), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Lebanese University [Beirut]
Subjects: 0301 basic medicine, penicillium expansum, Cell Survival, [SDV]Life Sciences [q-bio], Health, Toxicology and Mutagenesis, Genes, Fungal, 030106 microbiology, Mutant, toxicologie alimentaire, HL-60 Cells, Biology, Toxicology, Patulin, 03 medical and health sciences, chemistry.chemical_compound, Isomerism, Humans, Furans, Cytotoxicity, Mycotoxin, Dose-Response Relationship, Drug, ATP synthase, Microarray analysis techniques, Penicillium, patulin synthase, patuline, Hep G2 Cells, General Medicine, biology.organism_classification, patE gene, HEK293 Cells, 030104 developmental biology, chemistry, Biochemistry, Organ Specificity, Cell culture, biology.protein, cytotoxicity, microarray analysis, Caco-2 Cells, Penicillium expansum, ascladiol, Gene Deletion
Abstract: Patulin is the main mycotoxin contaminating apples. During the brewing of alcoholic beverages, this mycotoxin is degraded to ascladiol, which is also the last precursor of patulin. The present study aims (1) to characterize the last step of the patulin biosynthetic pathway and (2) to describe the toxicity of ascladiol. A patE deletion mutant was generated in Penicillium expansum. In contrast to the wild strain, this mutant does not produce patulin but accumulates high levels of E-ascladiol with few traces of Z-ascladiol. This confirms that patE encodes the patulin synthase involved in the conversion of E-ascladiol to patulin. After purification, cytotoxicities of patulin and E- and Z-ascladiol were investigated on human cell lines from liver, kidney, intestine, and immune system. Patulin was cytotoxic for these four cell lines in a dose-dependent manner. By contrast, both E- and Z-ascladiol were devoid of cytotoxicity. Microarray analyses on human intestinal cells treated with patulin and E-ascladiol showed that the latter, unlike patulin, did not alter the whole human transcription. These results demonstrate that E- and Z-ascladiol are not toxic and therefore patulin detoxification strategies leading to the accumulation of ascladiol are good approaches to limit the patulin risk.
Published: 2016

22. Short exposure to cold atmospheric plasma induces senescence in human skin fibroblasts and adipose mesenchymal stromal cells

Author: Noémie Juin, Marion Bourdens, Anne-Laure Bulteau, Yannick Jeanson, Valérie Planat-Benard, Marion Taurand, Louis Casteilla, Audrey Carrière, Franck Clement, Blanc, Sylvie, STROMALab, 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-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), Institut des sciences analytiques et de physico-chimie pour l'environnement et les materiaux (IPREM), Université de Pau et des Pays de l'Adour (UPPA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Génomique Fonctionnelle de Lyon (IGFL), École normale supérieure - Lyon (ENS Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Université de Pau et des Pays de l'Adour (UPPA)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), École normale supérieure de Lyon (ENS de Lyon)-Institut National de la Recherche Agronomique (INRA)-Université Claude Bernard Lyon 1 (UCBL), Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Etablissement Français du Sang-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-École normale supérieure - Lyon (ENS Lyon)
Subjects: Cyclin-Dependent Kinase Inhibitor p21, 0301 basic medicine, Senescence, Cell biology, [CHIM.POLY] Chemical Sciences/Polymers, Programmed cell death, Time Factors, [CHIM.ANAL] Chemical Sciences/Analytical chemistry, Stromal cell, Plasma Gases, Primary Cell Culture, lcsh:Medicine, Adipose tissue, Human skin, Helium, Article, 03 medical and health sciences, 0302 clinical medicine, [CHIM.ANAL]Chemical Sciences/Analytical chemistry, Humans, lcsh:Science, Cellular Senescence, Cyclin-Dependent Kinase Inhibitor p16, Skin, Skin repair, [CHIM.MATE] Chemical Sciences/Material chemistry, Multidisciplinary, Chemistry, Cell Cycle, lcsh:R, Mesenchymal stem cell, Mesenchymal Stem Cells, [CHIM.MATE]Chemical Sciences/Material chemistry, Fibroblasts, Phenotype, Mitochondria, 3. Good health, [CHIM.THEO]Chemical Sciences/Theoretical and/or physical chemistry, [CHIM.THEO] Chemical Sciences/Theoretical and/or physical chemistry, [CHIM.POLY]Chemical Sciences/Polymers, 030104 developmental biology, Adipose Tissue, Gene Expression Regulation, lcsh:Q, Tumor Suppressor Protein p53, 030217 neurology & neurosurgery, Signal Transduction
Abstract: Cold Atmospheric Plasma (CAP) is a novel promising tool developed in several biomedical applications such as cutaneous wound healing or skin cancer. Nevertheless, in vitro studies are lacking regarding to CAP effects on cellular actors involved in healthy skin healing and regarding to the mechanism of action. In this study, we investigated the effect of a 3 minutes exposure to CAP-Helium on human dermal fibroblasts and Adipose-derived Stromal Cells (ASC) obtained from the same tissue sample. We observed that CAP treatment did not induce cell death but lead to proliferation arrest with an increase in p53/p21 and DNA damages. Interestingly we showed that CAP treated dermal fibroblasts and ASC developed a senescence phenotype with p16 expression, characteristic morphological changes, Senescence-Associated β-galactosidase expression and the secretion of pro-inflammatory cytokines defined as the Senescence-Associated Secretory Phenotype (SASP). Moreover this senescence phenotype is associated with a glycolytic switch and an increase in mitochondria content. Despite this senescence phenotype, cells kept in vitro functional properties like differentiation potential and immunomodulatory effects. To conclude, we demonstrated that two main skin cellular actors are resistant to cell death but develop a senescence phenotype while maintaining some functional characteristics after 3 minutes of CAP-Helium treatment in vitro.
Published: 2019

23. Circumferential Contouring of the Lower Trunk: Indications, Operative Techniques, and Outcomes—A Systematic Review

Author: Benoit Chaput, Nicolas Bertheuil, Raphael Carloni, Christian Herlin, Paul Girard, Antoine De Runz, Eric Watier, Service de chirurgie plastique, reconstructive et esthétique [Rennes] = Cosmetic Reconstructive and Plastic surgery [Rennes], CHU Pontchaillou [Rennes], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire de Rangueil, Department of Plastic and Craniofacial Pediatric Surgery, Hôpital Lapeyronie [Montpellier] (CHU), Médialab (Sciences Po) (Médialab), Sciences Po (Sciences Po), Microenvironnement et cancer (MiCa), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Etablissement français du sang [Rennes] (EFS Bretagne), STROMALab, Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Etablissement Français du Sang-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de chirurgie plastique, reconstructive et esthétique, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-CHU Pontchaillou [Rennes]-Hôpital Sud, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), médialab (Sciences Po) (médialab), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Chard-Hutchinson, Xavier, Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), and Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS)
Subjects: Male, massive-weight-loss, medicine.medical_treatment, Belt lipectomy, lower-body lift, 030230 surgery, 0302 clinical medicine, Quality of life, Medicine, Abdominoplasty, Torso, nutritional deficiency, Middle Aged, Obesity, Morbid, 3. Good health, Treatment Outcome, loss patient, Waistline, Thigh, Patient Satisfaction, 030220 oncology & carcinogenesis, Body Composition, Female, thigh-buttock lift, Adult, medicine.medical_specialty, Esthetics, bariatric surgery, venous thromboembolism, [SDV.CAN]Life Sciences [q-bio]/Cancer, autologous gluteal augmentation, 03 medical and health sciences, Patient satisfaction, [SDV.CAN] Life Sciences [q-bio]/Cancer, Weight Loss, Humans, Surgery, Plastic, Postoperative Care, business.industry, Wound dehiscence, Evidence-based medicine, medicine.disease, belt lipectomy, high-lateral-tension, Surgery, Otorhinolaryngology, Quality of Life, Buttocks, business
Abstract: International audience; Background - Increasing obesity prevalence and development of bariatric surgery have led to the development of skin re-draping techniques. Several contouring techniques have been described for treating the circumferential excess of the lower trunk. Materials and methods - We performed a systematic review to summarize surgical indications, operative techniques, peri-operative management (nutritional supplementation, antibiotic prophylaxis, thrombo-prophylaxis), outcomes, complications, patient satisfaction, and impact on quality of life of circumferential contouring of the lower trunk procedures. A systematic review, based on the PRISMA criteria, was conducted using the Pubmed and Cochrane databases. Results - The review included 42 articles and 1748 operated patients. Two studies only were graded as level of evidence II; the others were graded as levels III to V. The most frequently reported indication was massive weight loss. All the described techniques derived either from belt lipectomy or lower bodylift. Belt lipectomy resulted in a posterior scar situated at the waistline and allowed a better correction of hip back rolls, whereas lower bodylift was more effective on buttock and lateral thigh ptosis. The most reported complication was wound dehiscence. Patient satisfaction and quality of life scores were high in all studies. Conclusions - This review included a majority of low-level evidence studies that limit extrapolability of the results. Future randomized prospective studies may generate stronger evidence, with a standardization of surgical indications and operative techniques. Level of evidence iii - This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Published: 2016

24. A French crop-exposure matrix for use in epidemiological studies on pesticides: PESTIMAT

Author: Baldi, Isabelle, Carles, Camille, Blanc-Lapierre, Audrey, Fabbro-Peray, Pascale, Druet-Cabanac, Michel, Boutet-Robinet, Elisa, Soulat, Jean-Marc, Bouvier, Ghislaine, Lebailly, Pierre, Group, The PESTIMAT, Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Bordeaux [Bordeaux], BESPIM, Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Aide à la Décision pour une Médecine Personnalisé - Laboratoire de Biostatistique, Epidémiologie et Recherche Clinique - EA 2415 (AIDMP), Université Montpellier 1 (UM1)-Université de Montpellier (UM), Neuroépidémiologie Tropicale (NET), Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM)-CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), 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-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], Cancers et préventions, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU), Centre Régional de Lutte contre le Cancer François Baclesse (CRLC François Baclesse ), Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CHU Limoges-Institut d'Epidémiologie Neurologique et de Neurologie Tropicale-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST), Université de Limoges (UNILIM)-Université de Limoges (UNILIM), Contaminants & Stress Cellulaire (ToxAlim-COMICS), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), 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 la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), and The study was supported by grants from the Agence Nationale de la Recherche (ANR), and the Institut National du Cancer (INCA, Canceropole Grand Sud-Ouest).
Subjects: Crops, Agricultural, medicine.medical_specialty, Databases, Factual, Epidemiology, occupational exposures, Health protection, Toxicology, Crop, 03 medical and health sciences, exposure matrix, 0302 clinical medicine, Occupational Exposure, Surveys and Questionnaires, Environmental health, Humans, Medicine, 030212 general & internal medicine, Duration (project management), agriculture, Exposure assessment, [SDV.EE]Life Sciences [q-bio]/Ecology, environment, 2. Zero hunger, business.industry, Public Health, Environmental and Occupational Health, Environmental Exposure, pesticides, Pesticide, crops, 030210 environmental & occupational health, Pollution, Agriculture, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Environmental Pollutants, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Christian ministry, France, Epidemiologic Methods, business, Environmental Monitoring
Abstract: International audience; Pesticide exposure assessment is a key methodological issue for epidemiological studies. The history of pesticide has proven difficult to obtain from individuals' report because of the wide range of active ingredients (AIs). We developed a crop-exposure matrix, which intends to reconstitute parameters of pesticide exposure in France since 1950. PESTIMAT is composed of tables crossing crops and AIs by year and providing the following metrics: (1) probability (proportion of farmers having used the AIs); (2) frequency (number of treatment days); and (3) intensity (application rate of the AIs in kg/ha). Metrics were obtained by the combination of six sources: (i) registration information from the Agriculture Ministry; (ii) information from agricultural bodies on products marketed; (iii) agricultural recommendations by the Plant Health Protection body; (iv) treatment calendars provided by farmers; (v) data from associations of farmers; and (vi) data from the industry. To date, 529 AIs usable between 1950 and 2010 are included in PESTIMAT: 160 fungicides; 160 herbicides; and 209 insecticides. When combined with duration and determinants of intensity, the metrics in PESTIMAT will make it possible to calculate exposure scores and to search for dose-effect relationships, an important criterion for causality judgment in epidemiology.
Published: 2015

25. Impact of maternal obesity on the metabolic profiles of pregnant women and their offspring at birth

Author: Cécile Canlet, Nathalie Bonvallot, Romain Desert, Nathalie Costet, Sylvaine Cordier, Jonchère, Laurent, 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 ), Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), École des Hautes Études en Santé Publique [EHESP] (EHESP), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-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 la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaboHUB-MetaToul, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-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 Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-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 Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, We acknowledge financial support from the EHESP School of Public Health, France., 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), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-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 la Recherche Agronomique (INRA)-MetaToul-MetaboHUB, Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-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)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaToul-MetaboHUB, MetaToul AXIOM (E20), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-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 Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and Université de Toulouse (UT)-Université de Toulouse (UT)
Subjects: medicine.medical_specialty, System biology, Offspring, Biomedicine general, [SDV]Life Sciences [q-bio], Endocrinology, Diabetes and Metabolism, Birth weight, Clinical Biochemistry, Physiology, Overweight, Biology, Biochemistry, Excretion, Pregnancy, Maternal obesity, Internal medicine, medicine, Metabolomics, Obesity, 2. Zero hunger, Cell Biology, medicine.disease, 3. Good health, [SDV] Life Sciences [q-bio], Endocrinology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Molecular Medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Apgar score, medicine.symptom, Body mass index, Biomarkers, Developmental Biology
Abstract: International audience; Obesity is currently an increasing public health problem. The intra-uterine environment plays a critical role in foetal development. The objective of this study is to investigate the association of obesity with modifications in the metabolic profiles of pregnant women, and their new-borns. Based on the PELAGIE cohort (Brittany, France), a sample of 321 pregnant women was divided into three groups according to their body mass index (BMI) (normal, over-weight and obese). Nuclear magnetic resonance-based metabolomics analyses were performed on maternal urine and cord-blood samples. Partial least squares regression-discriminant analysis (PLS-DA), polytomous and logistic regressions were used to differentiate the metabolic profiles of the three BMI groups after adjusting for potential confounders. Specific profiles were observed for the overweight and obese women (BMI > 25) compared to the normal-weight women: they had a decrease in urinary hippurate excretion associated with a decrease in phenylalanine and an increase in creatinine. We also showed an increase in the urinary excretion of lactate, citrate, acetate, creatine, and lysine only in obese women (BMI > 30) compared to the normal-weight women. The PLS-DA modelling did not reveal any significant difference between the cord-blood metabolic profiles of newborns according to maternal BMI—although infants born of obese women had a higher birth weight and a lower Apgar score. Our results confirmed the potential link between obesity and gut microbiota disruption (changes in urinary acids), as well as energy and amino-acid metabolism but did not reveal any disruption among newborns.
Published: 2015

26. Genome sequence of an aflatoxigenic pathogen of Argentinian peanut, Aspergillus arachidicola

Author: Olivier Puel, Brian M. Mack, Geromy G. Moore, Shannon B. Beltz, Moore, Geromy G, Southern Regional Research Center, USDA-ARS : Agricultural Research Service, Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-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 la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées
Subjects: 0301 basic medicine, lcsh:QH426-470, Arachis, lcsh:Biotechnology, [SDV]Life Sciences [q-bio], 030106 microbiology, Aspergillus arachidicola, Biology, Genome, Fungal Proteins, 03 medical and health sciences, food, Aflatoxins, lcsh:TP248.13-248.65, Genetics, Blast2GO, Genome size, Gene, Plant Diseases, 2. Zero hunger, Whole genome sequencing, Aspergillus, Fungal protein, Gene Expression Profiling, Phylogenomics, High-Throughput Nucleotide Sequencing, Molecular Sequence Annotation, biology.organism_classification, food.food, aspergillus arachidicola, phylogenomics, mating-type locus, genome sequence, gene ontology, lcsh:Genetics, Gene Ontology, 030104 developmental biology, Genome sequence, Mating-type locus, Genome, Fungal, Transcriptome, Research Article, Biotechnology, Brazil nut
Abstract: Background Aspergillus arachidicola is an aflatoxigenic fungal species, first isolated from the leaves of a wild peanut species native to Argentina. It has since been reported in maize, Brazil nut and human sputum samples. This aflatoxigenic species is capable of secreting both B and G aflatoxins, similar to A. parasiticus and A. nomius. It has other characteristics that may result in its misidentification as one of several other section Flavi species. This study offers a preliminary analysis of the A. arachidicola genome. Results In this study we sequenced the genome of the A. arachidicola type strain (CBS 117610) and found its genome size to be 38.9 Mb, and its number of predicted genes to be 12,091, which are values comparable to those in other sequenced Aspergilli. A comparison of 57 known Aspergillus secondary metabolite gene clusters, among closely-related aflatoxigenic species, revealed nearly half were predicted to exist in the type strain of A. arachidicola. Of its predicted genes, 691 were identified as unique to the species and 60% were assigned Gene Ontology terms using BLAST2GO. Phylogenomic inference shows CBS 117610 sharing a most recent common ancestor with A. parasiticus. Finally, BLAST query of A. flavus mating-type idiomorph sequences to this strain revealed the presence of a single mating-type (MAT1–1) idiomorph. Conclusions Based on A. arachidicola morphological, genetic and chemotype similarities with A. flavus and A. parasiticus, sequencing the genome of A. arachidicola will contribute to our understanding of the evolutionary relatedness among aflatoxigenic fungi. Electronic supplementary material The online version of this article (10.1186/s12864-018-4576-2) contains supplementary material, which is available to authorized users.
Published: 2018

27. Time course study of the response to LPS targeting the pig immune gene networks

Author: Darya Bazovkina, Laure Gress, Laurence Liaubet, Pierre Mormède, Valérie Sautron, Nathalie Villa-Vialaneix, Elena Terenina, Caroline Ydier, Yannick Lippi, Amélie Sevin-Pujol, Yvon Billon, Claire Naylies, Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Russian Academy of Science, Siberian Branch, Department of Behavioral Neurogenomics, Partenaires INRAE, Transcriptomic impact of Xenobiotics (E23 TRiX), ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), 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 la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Génétique, Expérimentation et Système Innovants (GenESI), Institut National de la Recherche Agronomique (INRA), Unité de Mathématiques et Informatique Appliquées de Toulouse (MIAT INRA), ANR-12-ADAP-0008, Région Midi-Pyrénées, Embassy of France in Russia (Mechnikov Program)., Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-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 Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: Lipopolysaccharides, Male, 0301 basic medicine, Candidate gene, Stress, Hypothalamic, pituitary-adrenal (HPA) axis, Cortisol, Time-course, Systems biology, Microarray, Pig, PORCINE PBMCS, SIGNIFICANTLY INFLUENCES, TRANSCRIPTOMIC ANALYSIS, MOLECULAR-GENETICS, GROWING PIGS, EXPRESSION, INNATE, SWINE, LIPOPOLYSACCHARIDE, ACTIVATION, Hydrocortisone, Lipopolysaccharide, Swine, [SDV]Life Sciences [q-bio], chemistry.chemical_compound, 0302 clinical medicine, Gene Regulatory Networks, [MATH]Mathematics [math], Hypothalamic-pituitary-adrenal (HPA) axis, Whole blood, 2. Zero hunger, medicine.anatomical_structure, Female, medicine.symptom, Research Article, Biotechnology, medicine.drug, lcsh:QH426-470, lcsh:Biotechnology, Inflammation, Biology, 03 medical and health sciences, lcsh:TP248.13-248.65, White blood cell, Genetics, medicine, Animals, [INFO]Computer Science [cs], [SDV.GEN]Life Sciences [q-bio]/Genetics, Gene Expression Profiling, Immunity, Blood Cell Count, Gene expression profiling, lcsh:Genetics, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, Kinetics, 030104 developmental biology, chemistry, Immunology, Transcriptome, 030217 neurology & neurosurgery
Abstract: Background Stress is a generic term used to describe non-specific responses of the body to all kinds of challenges. A very large variability in the response can be observed across individuals, depending on numerous conditioning factors like genetics, early influences and life history. As a result, there is a wide range of individual vulnerability and resilience to stress, also called robustness. The importance of robustness-related traits in breeding strategies is increasing progressively towards the production of animals with a high level of production under a wide range of climatic conditions and management systems, together with a lower environmental impact and a high level of animal welfare. The present study aims at describing blood transcriptomic, hormonal, and metabolic responses of pigs to a systemic challenge using lipopolysaccharide (LPS). The objective is to analyze the individual variation of the biological responses in relation to the activity of the HPA axis measured by the levels of plasma cortisol after LPS and ACTH in 120 juvenile Large White (LW) pigs. The kinetics of the response was measured with biological variables and whole blood gene expression at 4 time points. A multilevel statistical analysis was used to take into account the longitudinal aspect of the data. Results Cortisol level reaches its peak 4 h after LPS injection. The characteristic changes of white blood cell count to LPS were observed, with a decrease of total count, maximal at t=+4 h, and the mirror changes in the respective proportions of lymphocytes and granulocytes. The lymphocytes / granulocytes ratio was maximal at t=+1 h. An integrative statistical approach was used and provided a set of candidate genes for kinetic studies and ongoing complementary studies focused on the LPS-stimulated inflammatory response. Conclusions The present study demonstrates the specific biomarkers indicative of an inflammation in swine. Furthermore, these stress responses persist for prolonged periods of time and at significant expression levels, making them good candidate markers for evaluating the efficacy of anti-inflammatory drugs. Electronic supplementary material The online version of this article (doi:10.1186/s12864-017-4363-5) contains supplementary material, which is available to authorized users.
Published: 2017

28. Gut dysbiosis and impairment of immune system homeostasis in perinatally-exposed mice to Bisphenol A precede obese phenotype development

Author: Nancy Geoffre, Eric Houdeau, Sandrine Ménard, Laurence Guzylack-Piriou, Christel Cartier, Corinne Lencina, Frédéric Lasserre, Maïwenn Olier, Cherryl Harkat, Yann Malaisé, Eric Gaultier, Isabelle Castan, Laila Lakhal, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), 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-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Endocrinologie & Toxicologie de la Barrière Intestinale (ToxAlim-ENTeRisk), Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), Institut National de la Santé et de la Recherche Médicale (INSERM), Exposition, Perturbation Endocrino-métabolique et Reproduction (ToxAlim-EXPER), This work was supported by grant ANR-10-CESA-005 from the Agence Nationale de la recherche, (France), grant EST-2015/1/026 from Agence Nationale de Securite Sanitaire, de l'Alimentation, de l'Environnement et du Travail (ANSES), grant from AlimH from the Institut National de la Recherche Agronomique (INRA) and grant from the Region of Midi-Pyrénées, ProdInra, Migration, Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Houdeau, Eric, and Guzylack-Piriou, Laurence
Subjects: Male, 0301 basic medicine, Time Factors, [SDV]Life Sciences [q-bio], toxicologie alimentaire, lcsh:Medicine, microbiote digestif, White adipose tissue, Feces, 0302 clinical medicine, Pregnancy, période perinatale, Longitudinal Studies, lcsh:Science, Mice, Inbred C3H, Multidisciplinary, Perinatal Exposure, Metabolic disorder, 3. Good health, [SDV] Life Sciences [q-bio], obésité, medicine.anatomical_structure, Prenatal Exposure Delayed Effects, Environmental Pollutants, Female, medicine.symptom, endocrine system, medicine.medical_specialty, Inflammation, Article, 03 medical and health sciences, Immune system, Phenols, Internal medicine, medicine, Animals, bisphénol a, Obesity, Benzhydryl Compounds, Lamina propria, urogenital system, business.industry, lcsh:R, medicine.disease, Gastrointestinal Microbiome, Immunoglobulin A, Glucose, 030104 developmental biology, Endocrinology, Animals, Newborn, Ageing, Immune System, Dysbiosis, lcsh:Q, business, 030217 neurology & neurosurgery, Homeostasis
Abstract: Epidemiology evidenced the Bisphenol A (BPA), a chemical found in daily consumer products, as an environmental contributor to obesity and type II diabetes (T2D) in Humans. However, the BPA-mediated effects supporting these metabolic disorders are still unknown. Knowing that obesity and T2D are associated with low-grade inflammation and gut dysbiosis, we performed a longitudinal study in mice to determine the sequential adverse effects of BPA on immune system and intestinal microbiota that could contribute to the development of metabolic disorders. We observed that perinatal exposure to BPA (50 µg/kg body weight/day) induced intestinal and systemic immune imbalances at PND45, through a decrease of Th1/Th17 cell frequencies in the lamina propria concomitant to an increase of splenic Th1/Th17 immune responses. These early effects are associated with an altered glucose sensitivity, a defect of IgA secretion into faeces and a fall of faecal bifidobacteria relative to control mice. Such BPA-mediated events precede infiltration of pro-inflammatory M1 macrophages in gonadal white adipose tissue appearing with ageing, together with a decreased insulin sensitivity and an increased weight gain. Our findings provide a better understanding of the sequential events provoked by perinatal exposure to BPA that could support metabolic disorder development in later life.
Published: 2017

29. A large diversity of lactic acid bacteria species is involved in the fermentation of wheat used for the manufacture of lemzeiet

Author: Anne Thierry, Sylviane Bailly, Ryma Merabti, Florence Valence, Marie Noelle Madec, Victoria Chuat, Marie Bernadette Maillard, Farida Bekhouche, Science et Technologie du Lait et de l'Oeuf (STLO), Institut National de la Recherche Agronomique (INRA)-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), Département de Biotechnologie Alimentaire, Institut de la Nutrition, de l’Alimentation et des Technologies Agro‑alimentaires (INATAA), Université de Constantine, ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-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, PNE scholarship program provided by the Algerian Ministry of Higher Education and Scientific Research in UMR1253 INRA—Rennes, France, Toxicologie Alimentaire (UTA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Science et Technologie du Lait et de l'Oeuf ( STLO ), Institut National de la Recherche Agronomique ( INRA ) -AGROCAMPUS OUEST, Université Constantine 1, Toxicologie Alimentaire ( UTA ), and Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement
Subjects: Weissella, [ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition, bactérie lactique, Biochemistry, composé aromatique, Industrial and Manufacturing Engineering, 03 medical and health sciences, chemistry.chemical_compound, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, Lactobacillus, [SDV.IDA]Life Sciences [q-bio]/Food engineering, Botany, Leuconostoc, Food science, couscous algérien, fermentation, ceréale, 030304 developmental biology, 2. Zero hunger, 0303 health sciences, biology, 030306 microbiology, [ SDV.IDA ] Life Sciences [q-bio]/Food engineering, vinaigre, food and beverages, General Chemistry, biology.organism_classification, lemzeiet, Lactic acid, carbohydrates (lipids), [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, chemistry, Enterococcus, Fermentation, Pediococcus, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Bacteria, Food Science, Biotechnology
Abstract: Algerian couscous named lemzeiet is manufactured from fermented wheat. Historically performed in underground silos called matmor, the fermentation of wheat is now generally carried out in plastic jerrycans with or without addition of vinegar at the beginning of the fermentation. Culture-dependent and culture-independent methods (PCR-TTGE) were used to characterize lactic acid bacteria and to determine their dynamic and diversity over a two-year period, with and without the addition of vinegar. Fungi, physicochemical characteristics, and volatile compound profiles were also monitored. The isolates obtained from different stages of fermentation and from both processes were characterized by coupling different molecular methods (16SrRNA/pheS/rpoA gene sequencing, species-specific PCR, RAPD and PFGE). PCR-TTGE revealed very similar profiles for both processes. Sixty-nine isolates were identified as belonging to six genera of 16 species (Enterococcus, Lactobacillus, Leuconostoc, Pediococcus, Weissella, and Streptococcus). The profiles of volatile aroma compounds showed a marked effect of the fermentation process, compared to non-fermented wheat, with 35 of the 40 volatiles detected at amounts 20- to 30-fold higher in fermented wheat samples. This study gives the first insight into lactic acid bacteria population diversity and activity in fermented wheat and will contribute to a better control of the fermentation process.
Published: 2015

30. New insights into the organ-specific adverse effects of fumonisin B1: comparison between lung and liver

Author: Hervé Guillou, Isabelle P. Oswald, Nicole Therville, Arnaud Polizzi, Nicolas Loiseau, Aude Dupuy, Anne-Marie Cossalter, Thierry Levade, Jean-Denis Bailly, Jean-Luc Viadere, Justine Bertrand-Michel, Jennifer Loy, Mirindra Rakotonirainy, Olivier Puel, Martine Kolf-Clauw, Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), 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-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Franco-czech Laboratory for clinical research on obesity, Charles University [Prague]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches en Cancérologie de Toulouse (CRCT), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées, Plateforme Ezop (Ezop), Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), Region Midi-Pyrenees, France, Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Plateau MetaToul-LIPIDOMIQUE = MetaToul-Lipidomics, MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-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)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Région Midi-Pyrénées, France, 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)-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)-MetaToul-MetaboHUB, Université Fédérale Toulouse Midi-Pyrénées-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 Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaToul-MetaboHUB, Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), and Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Ceramide, Swine, [SDV]Life Sciences [q-bio], Health, Toxicology and Mutagenesis, [SDV.TOX.TVM]Life Sciences [q-bio]/Toxicology/Vegetal toxicology and mycotoxicology, [SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain, Biology, Pharmacology, Fusarium verticillioides, Toxicology, medicine.disease_cause, Fumonisins, 03 medical and health sciences, chemistry.chemical_compound, Sphingosine N-Acyltransferase, Fumonisin, medicine, Animals, Enzyme Inhibitors, Lung, 030304 developmental biology, Sphingolipids, 0303 health sciences, Fumonisin B1, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Toxin, Tumor Suppressor Proteins, 030302 biochemistry & molecular biology, Membrane Proteins, General Medicine, Pulmonary edema, medicine.disease, Sphingolipid, 3. Good health, carbohydrates (lipids), medicine.anatomical_structure, Liver, chemistry, Biochemistry, [SDV.TOX]Life Sciences [q-bio]/Toxicology, lipids (amino acids, peptides, and proteins), Sphingomyelin
Abstract: International audience; Fumonisin B1 (FB1) is a well-known inhibitor of de novo sphingolipid biosynthesis, due to its ability to inhibit ceramide synthases (CerS) activity. In mammals, this toxin triggers broad clinical symptoms with multi-organ dysfunction such as hepatotoxicity or pulmonary edema. The molecular mechanism of CerS inhibition by FB1 remains unknown. Due to the existence of six mammalian CerS isoforms with a tissue-specific expression pattern, we postulated that the organ-specific adverse effects of FB1 might be due to different CerS isoforms. The sphingolipid contents of lung and liver were compared in normal and FB1-exposed piglets (gavage with 1.5 mg FB1/kg body weight daily for 9 days). The effect of the toxin on each CerS was deduced from the analysis of its effects on individual ceramide (Cer) and sphingomyelin (SM) species. As expected, the total Cer content decreased by half in the lungs of FB1-exposed piglets, while in contrast, total Cer increased 3.5-fold in the livers of FB1-exposed animals. Our data also indicated that FB1 is more prone to bind to CerS4 and CerS2 to deplete lung and to enrich liver in d18:1/C20:0 and d18:1/C22:0 ceramides. It also interact with CerS1 to enrich liver in d18:1/C18:0 ceramides. Cer levels were counterbalanced by those of SM. In conclusion, these results demonstrate that the specificity of the effects of FB1 on tissues and organs is due to the effects of the toxin on CerS4, CerS2, and CerS1.
Published: 2014

31. Long noncoding RNA repertoire in chicken liver and adipose tissue

Author: Sylvain Foissac, Morgane Boutin, Valentin Wucher, Frédéric Jehl, Colette Désert, Elisabetta Giuffra, Diane Esquerre, Frédéric Lecerf, Sandrine Lagarrigue, Christophe Klopp, Kévin Muret, Thomas Derrien, Sarah Djebali, Fabrice Legeai, Hervé Acloque, BMC, BMC, Adapting the feed, the animal and the feeding techniques to improve the efficiency and sustainability of monogastric livestock production systems - Feed-a-Gene - - H20202015-03-01 - 2020-02-29 - 633531 - VALID, Physiologie, Environnement et Génétique pour l'Animal et les Systèmes d'Elevage [Rennes] (PEGASE), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Système d'Information des GENomes des Animaux d'Elevage (SIGENAE), Institut National de la Recherche Agronomique (INRA), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National de la Recherche Agronomique (INRA)-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-Institut National de la Santé et de la Recherche Médicale (INSERM), Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT], Institut de Génétique, Environnement et Protection des Plantes (IGEPP), Institut National de la Recherche Agronomique (INRA)-Université de Rennes (UR)-AGROCAMPUS OUEST, Génétique Animale et Biologie Intégrative (GABI), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, IN-1275570, INRA, European Project: 633531,H2020,H2020-SFS-2014-2,Feed-a-Gene(2015), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Toulouse (UT)-Université de Toulouse (UT)-École nationale supérieure agronomique de Toulouse (ENSAT), Université de Toulouse (UT)-Université de Toulouse (UT), 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 la Recherche Agronomique (INRA), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Institut National de la Recherche Agronomique (INRA)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Institut National de la Recherche Agronomique (INRA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-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), AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Recherche Agronomique (INRA), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), and AgroParisTech-Institut National de la Recherche Agronomique (INRA)
Subjects: 0301 basic medicine, Genotype, [SDV]Life Sciences [q-bio], Quantitative Trait Loci, poulet, génomique fonctionnelle, tissu adipeux, Adipose tissue, Biology, Genome, Evolution, Molecular, Transcriptome, Open Reading Frames, analyse de génome, 03 medical and health sciences, Genetics, Animals, Humans, RNA, Antisense, Genetics(clinical), RNA, Messenger, Gene, Conserved Sequence, Ecology, Evolution, Behavior and Systematics, Synteny, 030102 biochemistry & molecular biology, Gene Expression Profiling, General Medicine, Lipid Metabolism, foie, Phenotype, Long non-coding RNA, [SDV] Life Sciences [q-bio], Gene expression profiling, 030104 developmental biology, Adipose Tissue, Gene Expression Regulation, Liver, Organ Specificity, RNA, Long Noncoding, Animal Science and Zoology, Chickens, annotation fonctionnelle, Research Article
Abstract: Background Improving functional annotation of the chicken genome is a key challenge in bridging the gap between genotype and phenotype. Among all transcribed regions, long noncoding RNAs (lncRNAs) are a major component of the transcriptome and its regulation, and whole-transcriptome sequencing (RNA-Seq) has greatly improved their identification and characterization. We performed an extensive profiling of the lncRNA transcriptome in the chicken liver and adipose tissue by RNA-Seq. We focused on these two tissues because of their importance in various economical traits for which energy storage and mobilization play key roles and also because of their high cell homogeneity. To predict lncRNAs, we used a recently developed tool called FEELnc, which also classifies them with respect to their distance and strand orientation to the closest protein-coding genes. Moreover, to confidently identify the genes/transcripts expressed in each tissue (a complex task for weakly expressed molecules such as lncRNAs), we probed a particularly large number of biological replicates (16 per tissue) compared to common multi-tissue studies with a larger set of tissues but less sampling. Results We predicted 2193 lncRNA genes, among which 1670 were robustly expressed across replicates in the liver and/or adipose tissue and which were classified into 1493 intergenic and 177 intragenic lncRNAs located between and within protein-coding genes, respectively. We observed similar structural features between chickens and mammals, with strong synteny conservation but without sequence conservation. As previously reported, we confirm that lncRNAs have a lower and more tissue-specific expression than mRNAs. Finally, we showed that adjacent lncRNA-mRNA genes in divergent orientation have a higher co-expression level when separated by less than 1 kb compared to more distant divergent pairs. Among these, we highlighted for the first time a novel lncRNA candidate involved in lipid metabolism, lnc_DHCR24, which is highly correlated with the DHCR24 gene that encodes a key enzyme of cholesterol biosynthesis. Conclusions We provide a comprehensive lncRNA repertoire in the chicken liver and adipose tissue, which shows interesting patterns of co-expression between mRNAs and lncRNAs. It contributes to improving the structural and functional annotation of the chicken genome and provides a basis for further studies on energy storage and mobilization traits in the chicken. Electronic supplementary material The online version of this article (doi:10.1186/s12711-016-0275-0) contains supplementary material, which is available to authorized users.
Published: 2017

32. Cell resistance to the Cytolethal Distending Toxin involves an association of DNA repair mechanisms

Author: Julien Vignard, Bernard Salles, Yann Malaisé, Elisa Boutet-Robinet, Aurore Loeuillet, Gladys Mirey, Marianne Chevalier, Elisabeth Bezine, Mirey, Gladys, Vignard, Julien, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), 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-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Contaminants & Stress Cellulaire (ToxAlim-COMICS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Génotoxicité & Signalisation (ToxAlim-GS), Agence Nationale de la Recherche (ANR) program [ANR-10-CESA-011], Institut National de la Recherche Agronomique, INP (Institut National Polytechnique de Toulouse), Université Fédérale Toulouse Midi-Pyrénées, Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées
Subjects: DNA Replication, 0301 basic medicine, DNA End-Joining Repair, Cytolethal distending toxin, DNA repair, DNA damage, [SDV]Life Sciences [q-bio], Bacterial Toxins, Biology, Article, 03 medical and health sciences, Fanconi anemia, medicine, Humans, DNA Breaks, Double-Stranded, Homologous Recombination, Multidisciplinary, 030102 biochemistry & molecular biology, Mutagenesis, HCT116 Cells, medicine.disease, Cell biology, Non-homologous end joining, 030104 developmental biology, Homologous recombination, HeLa Cells, Nucleotide excision repair
Abstract: The Cytolethal Distending Toxin (CDT), produced by many bacteria, has been associated with various diseases including cancer. CDT induces DNA double-strand breaks (DSBs), leading to cell death or mutagenesis if misrepaired. At low doses of CDT, other DNA lesions precede replication-dependent DSB formation, implying that non-DSB repair mechanisms may contribute to CDT cell resistance. To address this question, we developed a proliferation assay using human cell lines specifically depleted in each of the main DNA repair pathways. Here, we validate the involvement of the two major DSB repair mechanisms, Homologous Recombination and Non Homologous End Joining, in the management of CDT-induced lesions. We show that impairment of single-strand break repair (SSBR), but not nucleotide excision repair, sensitizes cells to CDT, and we explore the interplay of SSBR with the DSB repair mechanisms. Finally, we document the role of the replicative stress response and demonstrate the involvement of the Fanconi Anemia repair pathway in response to CDT. In conclusion, our work indicates that cellular survival to CDT-induced DNA damage involves different repair pathways, in particular SSBR. This reinforces a model where CDT-related genotoxicity primarily involves SSBs rather than DSBs, underlining the importance of cell proliferation during CDT intoxication and pathogenicity.
Published: 2016

33. Cellular impact of combinations of endosulfan, atrazine, and chlorpyrifos on human primary hepatocytes and HepaRG cells after short and chronic exposures

Author: Roger Rahmani, Jean Pierre Cravedi, Patrick Rouimi, Georges de Sousa, Ahmad Nawaz, Andrej Razpotnik, ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-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, Génotoxicité & Signalisation (ToxAlim-GS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), INRA, French National Research Program [07-PNRA-006], ANSES [ES-021], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)
Subjects: Insecticides, Programmed cell death, Human hepatocytes, Cell Survival, [SDV]Life Sciences [q-bio], Health, Toxicology and Mutagenesis, Primary Cell Culture, Pharmacology, Biology, Toxicology, Cell Line, chemistry.chemical_compound, Cell Adhesion, Humans, Atrazine, Endosulfan, Cell Death, Herbicides, Liver cell, Cell Biology, Pesticide, Real-time cell monitoring, 3. Good health, chemistry, 13. Climate action, Chlorpyrifos, Toxicity, Hepatocytes, Environmental Pollutants, HepaRG, Transcriptome, Xenobiotic
Abstract: International audience; Chronic exposure to low doses of pesticides present in the environment is increasingly suspected to cause major health issues to humans. Toxicological evaluations become more complex when the exposure concerns chemical combinations. Atrazine, chlorpyrifos, and endosulfan are pesticides used worldwide in agriculture and are therefore currently found at residual levels in food and the environment, even in countries in which they are now banned. Our study aimed to use Real-Time Cell Impedance Analyzer to investigate changes in phenotypical status of primary human hepatocytes and differentiated HepaRG cells induced by short and chronic exposures to these three chemicals. In contrast to the traditionally used endpoint cytotoxicity test, this technology allows kinetic measurements in real-time throughout the entire experiment. Our data show significantly higher cytotoxic effects of mixtures as compared to individual pesticides and a greater susceptibility of human hepatocytes as compared to HepaRG to short-term exposure (24 h). Repeated exposure over 2 weeks to endosulfan and endosulfan-containing mixture induced HepaRG cell death in a time- and dose-dependent manner. Of the typical genes involved in metabolism and cell-response to xenobiotics, we found an exposure time- and condition-dependent deregulation of the expression of CYP3A4 and UGT1A in HepaRG cells exposed to low doses of pesticides and mixtures. Our data demonstrate the usefulness of real-time cell monitoring in long-term toxicological evaluations of co-exposure to xenobiotics. In addition, they support but at the same time highlight certain limitations in the use of HepaRG cells as the gold standard liver cell model in toxicity studies.
Published: 2013

34. Fungal lipochitooligosaccharide symbiotic signals in arbuscular mycorrhiza

Author: Fabienne Maillet, Hugues Driguez, Véréna Poinsot, Guillaume Bécard, Andreas Niebel, Laurence Cromer, Damien Formey, Jean Dénarié, Olivier André, Virginie Puech-Pagès, Eduardo Andres Martinez, Delphine Giraudet, Monique Gueunier, Alexandra Haouy, inconnu, Inconnu, Centre de Recherches sur les Macromolécules Végétales (CERMAV), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Joseph Fourier - Grenoble 1 (UJF), Unité mixte de recherche interactions plantes-microorganismes, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées, Evolution des Interactions Plantes-Microorganismes, Laboratoire de Recherche en Sciences Végétales (LRSV), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Metatoul - Agromix, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-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-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre de Recherches sur les Macromolécules Végétales, Centre National de la Recherche Scientifique (CNRS), EMD Crop BioScience, Charles-Leopold Mayer Prize, French Academy of Sciences, Institut National de la Recherche Agronomique, Carret, Michèle, Université Fédérale Toulouse Midi-Pyrénées-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 Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT)
Subjects: Lipopolysaccharides, EXTRACTS CHEMISTRY METABOLISM, 0106 biological sciences, ved/biology.organism_classification_rank.species, Plant Roots, 01 natural sciences, CHOMATOGRAPHY HIGH PRESSURE LIQUID, LIPOPOLYSACCHARIDES CHEMISTRY METABOLISM, Glomeromycota, Mycorrhizae, Mycorrhiza, Chromatography, High Pressure Liquid, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, Multidisciplinary, Endosymbiosis, Ecology, SIGNAL TRANSDUCTION, SYMBIOSIS, food and beverages, SPORES FUNGAL CHEMISTRY METABOLISM SYMBIOSIS, Spores, Fungal, GLOMEROMYCOTA METABOLISM, MEDICAGO TRUNCATULA CHEMISTRY GROWTH & DEVELOPMENT METABOLISM MICROBIOLOBY, Medicago truncatula, Daucus carota, Arbuscular mycorrhiza, MYCORRHIZAE METABOLISM, PLANT ROOTS CHEMISTRY GROWTH & DEVELOPMENT METABOLISM MICROBIOLOGY, CARBOHYDRATE SEQUENCE, CAROTA CHEMISTRY METABOLISM MICROBIOLOGY, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Biology, 03 medical and health sciences, Symbiosis, Terrestrial plant, Botany, MOLECULAR SEQUENCE DATA, PLANT, 030304 developmental biology, Plant Extracts, ved/biology, fungi, Fabaceae, 15. Life on land, biology.organism_classification, DAUCUS, AM, SUSTAINABLE DEVELOPMENT, 010606 plant biology & botany
Abstract: International audience; Arbuscular mycorrhiza (AM) is a root endosymbiosis between plants and glomeromycete fungi. It is the most widespread terrestrial plant symbiosis, improving plant uptake of water and mineral nutrients. Yet, despite its crucial role in land ecosystems, molecular mechanisms leading to its formation are just beginning to be unravelled. Recent evidence suggests that AM fungi produce diffusible symbiotic signals. Here we show that Glomus intraradices secretes symbiotic signals that are a mixture of sulphated and non-sulphated simple lipochitooligosaccharides (LCOs), which stimulate formation of AM in plant species of diverse families (Fabaceae, Asteraceae and Umbelliferae). In the legume Medicago truncatula these signals stimulate root growth and branching by the symbiotic DMI signalling pathway. These findings provide a better understanding of the evolution of signalling mechanisms involved in plant root endosymbioses and will greatly facilitate their molecular dissection. They also open the way to using these natural and very active molecules in agriculture.
Published: 2011

35. Maternal high-fat diet prevents developmental programming by early-life stress

Author: Pierre Delage, Amandine Lépinay, Muriel Darnaudéry, Sophie Layé, Jean Fioramonti, Marion Rincel, Vassilia Theodorou, Nutrition et Neurobiologie intégrée (NutriNeuro), Université Bordeaux Segalen - Bordeaux 2-Institut National de la Recherche Agronomique (INRA)-Université Sciences et Technologies - Bordeaux 1-Institut Polytechnique de Bordeaux-Ecole nationale supérieure de chimie, biologie et physique, ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-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, Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), This work was supported by the University of Bordeaux (BQR, Aide a l'installation nouvelle equipe), INRA (Action Prioritaire Dpt AlimH), Projet inter-regions Aquitaine et Midi-Pyrenees and by the French National Research Agency (IBISS project ANR-12-DSSA-0004). MR and ALL were supported by a stipend of the Ministere de l'Enseignement Superieur et de la Recherche, Nutrition et Neurobiologie intégrée (NutriNeur0), Ecole nationale supérieure de chimie, biologie et physique-Institut Polytechnique de Bordeaux-Université Sciences et Technologies - Bordeaux 1-Institut National de la Recherche Agronomique (INRA)-Université Bordeaux Segalen - Bordeaux 2, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)
Subjects: 0301 basic medicine, [SDV]Life Sciences [q-bio], Anxiety, Overweight, human health, 0302 clinical medicine, Lactation, rat, Maternal Behavior, Maternal deprivation, Maternal Deprivation, critère de stress, santé humaine, 3. Good health, système nerveux central, régime alimentaire, Psychiatry and Mental health, medicine.anatomical_structure, Prenatal Exposure Delayed Effects, Receptor, Serotonin, 5-HT1A, cerveau, Gestation, Female, Original Article, pregnancy, medicine.symptom, Psychology, medicine.medical_specialty, Offspring, Prefrontal Cortex, Diet, High-Fat, grossesse, Life Change Events, 03 medical and health sciences, Cellular and Molecular Neuroscience, comportement maternel, Internal medicine, medicine, Animals, Rats, Wistar, Biological Psychiatry, Brain-derived neurotrophic factor, Pregnancy, Brain-Derived Neurotrophic Factor, Body Weight, central nervous system, medicine.disease, Repressor Proteins, Disease Models, Animal, mothering ability, 030104 developmental biology, Endocrinology, Animals, Newborn, 030217 neurology & neurosurgery
Abstract: Anxiety disorders and depression are well-documented in subjects exposed to adverse childhood events. Recently, maternal obesity and/or maternal consumption of high-fat diets (HFD) have been also proposed as risk factors for offspring mental health. Here using an animal model in rats, we explored the combinatorial effects of a maternal HFD (40% of energy from fat without impact on maternal weight; during gestation and lactation) and maternal separation (MS) in offspring. In the prefrontal cortex (PFC) of pups, MS led to changes in the expression of several genes such as Bdnf (brain derived neurotrophic factor), 5HT-r1a (serotonin receptor 1a) and Rest4 (neuron-restrictive silencer element, repressor element 1, silencing transcription factor (Rest), splicing variant 4). Surprisingly, perinatal HFD strongly attenuated the developmental alterations induced by MS. Furthermore, maternal HFD totally prevented the endophenotypes (anxiety, spatial memory, social behavior, hypothalamic–pituitary–adrenal (HPA) axis response to stress, hippocampal neurogenesis and visceral pain) associated with MS at adulthood. Finally, we also demonstrated that HFD intake reduced anxiety and enhanced maternal care in stressed dams. Overall, our data suggest that a HFD restricted to gestation and lactation, which did not lead to overweight in dams, had limited effects in unstressed offspring, highlighting the role of maternal obesity, rather than fat exposure per se, on brain vulnerability during development.
Published: 2016

36. Extensive genomic diversity and selective conservation of virulence-determinants in enterohemorrhagic Escherichia coli strains of O157 and non-O157 serotypes

Author: Jean-Philippe Nougayrède, Eric Oswald, Yoshitoshi Ogura, Satoru Kuhara, Jun Terajima, Kousuke Tashiro, Keisuke Nakayama, Haruo Watanabe, Ken Kurokawa, Tetsuya Hayashi, Asadulghani, Tadasuke Ooka, Toru Tobe, Institut de Recherche en Santé Digestive (IRSD ), 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-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), University of Miyazaki, National Institute of Infectious Diseases, Interactions hôtes-agents pathogènes [Toulouse] (IHAP), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Nara Institute of Science and Technology, Kyushu University, and Osaka University
Subjects: Virulence Factors, [SDV]Life Sciences [q-bio], Prophages, Molecular Sequence Data, Virulence, Escherichia coli O157, medicine.disease_cause, Genome, Microbiology, Evolution, Molecular, 03 medical and health sciences, fluids and secretions, Plasmid, medicine, Gene, Escherichia coli, ComputingMilieux_MISCELLANEOUS, Oligonucleotide Array Sequence Analysis, 030304 developmental biology, Genetics, 0303 health sciences, Base Sequence, biology, 030306 microbiology, Research, Genetic Variation, Shiga toxin, Genomics, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Horizontal gene transfer, biology.protein, bacteria, Genome, Bacterial, Plasmids, Locus of enterocyte effacement
Abstract: Comparing the genomes of O157 and non-O157 enterohemorrhagic Escherichia coli (EHEC) strains reveals the selective conservation of a large number of virulence determinants., Background Enterohemorrhagic Escherichia coli (EHEC) O157 causes severe food-borne illness in humans. The chromosome of O157 consists of 4.1 Mb backbone sequences shared by benign E. coli K-12, and 1.4 Mb O157-specific sequences encoding many virulence determinants, such as Shiga toxin genes (stx genes) and the locus of enterocyte effacement (LEE). Non-O157 EHECs belonging to distinct clonal lineages from O157 also cause similar illness in humans. According to the 'parallel' evolution model, they have independently acquired the major virulence determinants, the stx genes and LEE. However, the genomic differences between O157 and non-O157 EHECs have not yet been systematically analyzed. Results Using microarray and whole genome PCR scanning analyses, we performed a whole genome comparison of 20 EHEC strains of O26, O111, and O103 serotypes with O157. In non-O157 EHEC strains, although genome sizes were similar with or rather larger than O157 and the backbone regions were well conserved, O157-specific regions were very poorly conserved. Around only 20% of the O157-specific genes were fully conserved in each non-O157 serotype. However, the non-O157 EHECs contained a significant number of virulence genes that are found on prophages and plasmids in O157, and also multiple prophages similar to, but significantly divergent from, those in O157. Conclusion Although O157 and non-O157 EHECs have independently acquired a huge amount of serotype- or strain-specific genes by lateral gene transfer, they share an unexpectedly large number of virulence genes. Independent infections of similar but distinct bacteriophages carrying these virulence determinants are deeply involved in the evolution of O157 and non-O157 EHECs.
Published: 2007

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