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1. Inhibition of angiogenesis and murine tumour growth by laminarin sulphate

Author

J. Donaldson, D.H. Paper, R. Hoffman, and H. Vogl

Subjects
Cancer Research, Angiogenesis, Basic fibroblast growth factor, Molecular Sequence Data, Neovascularization, Physiologic, Antineoplastic Agents, Chick Embryo, Biology, Models, Biological, Neovascularization, chemistry.chemical_compound, Laminarin, Mice, In vivo, Laminin, Polysaccharides, medicine, Animals, Fibrosarcoma, Cells, Cultured, Matrigel, Mice, Inbred C3H, Neovascularization, Pathologic, medicine.disease, bacterial infections and mycoses, Molecular biology, Drug Combinations, Oncology, chemistry, Carbohydrate Sequence, Immunology, biology.protein, Cattle, Proteoglycans, Collagen, Endothelium, Vascular, medicine.symptom, Research Article
Abstract

LAM S5 is a polysulphated derivative of the glucan laminarian that inhibits basic fibroblast growth factor (bFGF) binding and the bFGF-stimulated proliferation of fetal bovine heart endothelial (FBHE) cells. This report demonstrates that LAM S5 has anti-angiogenic activity, as shown by inhibition of tubule formation by endothelial cells cultured on Matrigel and inhibition of vascularisation of the chick chorioallantoic membrane. In addition, LAM S5 caused a tumour growth delay of the murine RIF-1 tumour of 2.6 days (P = 0.01). Images Figure 2

Published
1996

2. Elevated amounts of myocilin in the aqueous humor of transgenic mice cause significant changes in ocular gene expression

Author

Paul Russell, Walter Paper, Ernst R. Tamm, Dietrich A. Stephan, Sebastian Heersink, Rudolf Fuchshofer, and Markus Kroeber

Subjects
Genetically modified mouse, DNA, Complementary, genetic structures, Transgene, Blotting, Western, Mice, Transgenic, Biology, Article, Gene product, Aqueous Humor, Cellular and Molecular Neuroscience, Mice, Trabecular Meshwork, Gene expression, medicine, Animals, Humans, Eye Proteins, Gene, Myocilin, Cells, Cultured, Glycoproteins, Oligonucleotide Array Sequence Analysis, Regulation of gene expression, Reverse Transcriptase Polymerase Chain Reaction, Molecular biology, Sensory Systems, eye diseases, Ophthalmology, Cytoskeletal Proteins, medicine.anatomical_structure, Gene Expression Regulation, Trabecular meshwork, sense organs
Abstract

Myocilin is a 55-57kDa secreted glycoprotein and member of the olfactomedin family, which is mutated in some forms of primary open-angle glaucoma. To assess the effects of elevated amounts of myocilin on aqueous humor outflow dynamics in an in vivo system, transgenic betaB1-crystallin-MYOC mice have been developed that strongly overexpress myocilin in their eyes. The transgenic overexpression of myocilin results in an almost five-fold increase of secreted normal myocilin in the aqueous humor of betaB1-crystallin-MYOC mice. In the present study, we wanted to use betaB1-crystallin-MYOC as a tool to identify the response of ocular tissues to the presence of higher than normal amounts of myocilin, and to identify changes in gene expression that could help to shed light on the functional in vivo properties of myocilin. RNA was isolated from ocular tissues of betaB1-crystallin-MYOC mice and wild-type littermates. Changes in gene expression were determined by hybridization of gene microarrays and confirmed by real time RT-PCR and Western blotting. The expression of genes that had been found to be differentially regulated in betaB1-crystallin-MYOC mice was further analyzed in cultured human trabecular meshwork (HTM) cells treated with recombinant myocilin. Although betaB1-crystallin-MYOC mice do not have an obvious phenotype, a statistically significant up- and downregulation of several distinct genes was found when compared to gene expression in wild-type littermates. Among the genes that were found to be differentially regulated were Wasl, Ceacam1, and Spon2, which are involved in cell adhesion and cell-matrix interactions. Differences in expression were also found for Six1 which encodes for a transcription factor, and for Pftk1 whose gene product is a cdc2-related protein kinase. The expression of these genes was also found to be regulated in vitro in HTM cells treated with recombinant myocilin. Substantially higher amounts in ocular tissues of betaB1-crystallin-MYOC mice were found for connexin 46 and alphaB-crystallin. In addition, several genes that encode for olfactomedin proteins showed distinct changes in expression. Olfml3 was significantly downregulated, while Lphn1, Lphn2, and Lphn3 were significantly upregulated. Our findings support a role for myocilin in modulating cellular adhesion, and suggest functional processes that involve other proteins of the olfactomedin family.

Published
2008

3. Zika virus enhances monocyte adhesion and transmigration favoring viral dissemination to neural cells

Author

Emma Partiot, Nilda Vanesa Ayala-Nunez, Jacky G. Goetz, Gautier Follain, Judith R.E. Roels, Anita Eckly, Béatrice Uring-Lambert, Maxime Chazal, Raphael Gaudin, Gillian Hale, Frank M. J. Jacobs, Sandrine Bourdoulous, Orestis Faklaris, Sherif R. Zaki, Aurélie Hirschler, Nolwenn Jouvenet, Margot Carocci, Florian Bakoa, Sarah Cianférani, Christine Carapito, Frédéric Doussau, Brigid C. Bollweg, François Delalande, Institut de Recherche en Infectiologie de Montpellier (IRIM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA), Institut National de la Santé et de la Recherche Médicale (INSERM), Immuno-Rhumatologie Moléculaire, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA), Fédération de Médecine Translationnelle de Strasbourg (FMTS), Département Sciences Analytiques et Interactions Ioniques et Biomoléculaires (DSA-IPHC), Institut Pluridisciplinaire Hubert Curien (IPHC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Centers for Disease Control and Prevention [Atlanta] (CDC), Centers for Disease Control and Prevention, Swammerdam Institute for Life Sciences, University of Amsterdam [Amsterdam] (UvA)-Center for Neurosciences, Génomique virale et vaccination, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Université Paris Descartes - Paris 5 (UPD5), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), BioCampus Montpellier (BCM), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Biologie et pharmacologie des plaquettes sanguines: hémostase, thrombose, transfusion, Université de Strasbourg (UNISTRA)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Les Hôpitaux Universitaires de Strasbourg (HUS), Institut des Neurosciences Cellulaires et Intégratives (INCI), Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS), This work has received funding from the French State via the French National Research Agency (ANR) as part of the program Investissements d’avenir (IdEx Université de Strasbourg) to RG. This work was supported by an ATIP-AVENIR starting grant to RG. The research leading to these results has received funding from the People Program (Marie Curie Actions) of the European Union’s Seventh Framework Program (FP7/2007–2013) under REA grant agreement no. PCOFUND-GA-2013-609102, through the PRESTIGE program coordinated by Campus France, and from the French Agency for Research on AIDS and Viral Hepatitis (ANRS), both attributed to NVAN. Experiments conducted by G.F. and J.G.G. were funded by Plan Cancer (OptoMetaTrap), Ligue contre le Cancer, Idex Attractivités (University of Strasbourg), and by institutional funds from INSERM and University of Strasbourg. G.F. was supported by a doctoral fellowship from Ligue Contre le Cancer. Mass spectrometry experiments were supported by the French Proteomic Infrastructure (ProFI, ANR-10-INBS-08-03). F.B. is a recipient of a PhD grant provided by ANRT (Association Nationale de la Recherche et de la Technologie). N.J. is funded by Agence Nationale pour la Recherche (ANR-16-CE15-0025-01), Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur. CDC contributions to this paper written and edited by G.L.H. and B.C.B. in their private capacity. No official support or endorsement by the Centers for Disease Control and Prevention, Department of Health and Human Services is intended, nor should be inferred. All authors read, provided feedback, and approved the paper. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. The following reagent was obtained through the NIH AIDS Reagent Program, Division of AIDS, NIAID, NIH: HIV-1 NL4-3 AD8 Infectious Molecular Clone (pNL(AD8)) from Dr. Eric O. Freed (cat# 11346)., ANR-16-CE15-0025,Viro-Storm,Mécanismes de production incontrôlée de cytokines au cours de l'infection virale(2016), European Project: 609102,EC:FP7:PEOPLE,FP7-PEOPLE-2013-COFUND,PRESTIGE(2014), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), BioCampus (BCM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), EFS-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), jouvenet, nolwenn, Mécanismes de production incontrôlée de cytokines au cours de l'infection virale - - Viro-Storm2016 - ANR-16-CE15-0025 - AAPG2016 - VALID, PRES Towards International Gain of Excellence - PRESTIGE - - EC:FP7:PEOPLE2014-09-01 - 2019-08-31 - 609102 - VALID, Equipe Direction scientifique, Sciences et Technologies de la Musique et du Son (STMS), Université Pierre et Marie Curie - Paris 6 (UPMC)-IRCAM-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-IRCAM-Centre National de la Recherche Scientifique (CNRS), École pratique des hautes études (EPHE), Neuro-Immunologie Virale, Virologie UMR1161 (VIRO), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Laboratoire de Photonique Quantique et Moléculaire (LPQM), Centre National de la Recherche Scientifique (CNRS)-CentraleSupélec-École normale supérieure - Cachan (ENS Cachan), Biologie et pharmacologie des plaquettes sanguines: hémostase, thrombose, transfusion (http://www.u949.inserm.fr/), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-EFS, Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Spectrométrie de Masse BioOrganique, Département des Sciences Analytiques, Institut Pluridisciplinaire Hubert Curien, Strasbourg, France (LSMBO-DSA-IPHC), Centre National de la Recherche Scientifique (CNRS), Immunorhumathologie moléculaire, Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), and Molecular Neuroscience (SILS, FNWI)

Subjects
Central Nervous System, 0301 basic medicine, MESH: Neurons, General Physics and Astronomy, MESH: Organoids, MESH: Monocytes, Monocytes, Zika virus, 0302 clinical medicine, MESH: Transendothelial and Transepithelial Migration, Cerebellum, MESH: Animals, lcsh:Science, MESH: Embryonic Stem Cells, ComputingMilieux_MISCELLANEOUS, Zebrafish, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Neurons, Multidisciplinary, Zika Virus Infection, Cell adhesion molecule, food and beverages, Sciences du Vivant [q-bio]/Microbiologie et Parasitologie, Phenotype, 3. Good health, Cell biology, Organoids, Mechanisms of disease, medicine.anatomical_structure, MESH: Cell Survival, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, Endothelium, Cell Survival, Science, MESH: Zika Virus, Biology, MESH: Endothelium, Article, General Biochemistry, Genetics and Molecular Biology, Virus, MESH: Cell Adhesion, 03 medical and health sciences, Virology, medicine, Animals, Humans, MESH: Central Nervous System, Cellular microbiology, Cell adhesion, MESH: Zebrafish, Embryonic Stem Cells, MESH: Humans, Monocyte, fungi, Transendothelial and Transepithelial Migration, Zika Virus, General Chemistry, biology.organism_classification, Embryonic stem cell, MESH: Cerebellum, Disease Models, Animal, 030104 developmental biology, lcsh:Q, MESH: Disease Models, Animal, Cell Adhesion Molecules, MESH: Female, 030217 neurology & neurosurgery
Abstract

Zika virus (ZIKV) invades and persists in the central nervous system (CNS), causing severe neurological diseases. However the virus journey, from the bloodstream to tissues through a mature endothelium, remains unclear. Here, we show that ZIKV-infected monocytes represent suitable carriers for viral dissemination to the CNS using human primary monocytes, cerebral organoids derived from embryonic stem cells, organotypic mouse cerebellar slices, a xenotypic human-zebrafish model, and human fetus brain samples. We find that ZIKV-exposed monocytes exhibit higher expression of adhesion molecules, and higher abilities to attach onto the vessel wall and transmigrate across endothelia. This phenotype is associated to enhanced monocyte-mediated ZIKV dissemination to neural cells. Together, our data show that ZIKV manipulates the monocyte adhesive properties and enhances monocyte transmigration and viral dissemination to neural cells. Monocyte transmigration may represent an important mechanism required for viral tissue invasion and persistence that could be specifically targeted for therapeutic intervention., Zika virus (ZIKV) can infect the central nervous system, but it is not clear how it reaches the brain. Here, Ayala-Nunez et al. show in ex vivo and in vivo models that ZIKV can hitch a ride in monocytes in a Trojan Horse manner to cross the endothelium and disseminate the virus.

Published
2019

4. Pre- and Postnatal Dietary Exposure to a Pesticide Cocktail Disrupts Ovarian Functions in 8-Week-Old Female Mice

Author

Léonie Dopavogui, Florence Cadoret, Gaspard Loison, Sara El Fouikar, François-Xavier Frenois, Frank Giton, Sandrine Ellero-Simatos, Frédéric Lasserre, Arnaud Polizzi, Clémence Rives, Nicolas Loiseau, Roger D. Léandri, Nicolas Gatimel, Laurence Gamet-Payrastre, Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Toulouse [Toulouse], Développement Embryonnaire, Fertilité et Environnement (DEFE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Exposition, Perturbation Endocrino-métabolique et Reproduction (ToxAlim-EXPER), 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 Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), L.D. was supported by a Ph.D. grant from INRAE (Animal Health Department). This work was supported by a grant from the Ministry for Agriculture and Food and the Ministry for an Ecological and Solidary Transition, with the financial support of the French Biodiversity Agency (GepeTho), by ANR France (Syneract), and by Région Occitanie. This work also received funding from Agence de la Biomédecine (AOR 2019).This paper benefited from the Imag’IN Platform of the Institut Universitaire du Cancer from April 2019 to August 2021 https://www.imagin-labs.net/imagin_v2/index.php? lang=EN (last accessed on 5 June 2022). We thank X. Blanc from INRAe SAAJ (Jouy-en-Josas) for his technical support for pellet preparation., ANR-18-CE34-0009,SYNERACT,Activation synergique de recepteurs nucléaires(2018), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), 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), LESUR, Hélène, and APPEL À PROJETS GÉNÉRIQUE 2018 - Activation synergique de recepteurs nucléaires - - SYNERACT2018 - ANR-18-CE34-0009 - AAPG2018 - VALID

Subjects
pesticide, folliculogenesis, ovary, endocrine disruption, progesterone, [SDV]Life Sciences [q-bio], Organic Chemistry, Pesticide Residues, General Medicine, Catalysis, Computer Science Applications, [SDV] Life Sciences [q-bio], Inorganic Chemistry, Dietary Exposure, Mice, Fruit, Animals, Female, Chlorpyrifos, Physical and Theoretical Chemistry, Pesticides, Molecular Biology, Spectroscopy
Abstract

International audience; Female infertility has a multifactorial origin, and exposure to contaminants, including pesticides, with endocrine-disrupting properties is considered to be involved in this reproductive disorder, especially when it occurs during early life. Pesticides are present in various facets of the environment, and consumers are exposed to a combination of multiple pesticide residues through food intake. The consequences of such exposure with respect to female fertility are not well known. Therefore, we aimed to assess the impact of pre- and postnatal dietary exposure to a pesticide mixture on folliculogenesis, a crucial process in female reproduction. Mice were exposed to the acceptable daily intake levels of six pesticides in a mixture (boscalid, captan, chlorpyrifos, thiacloprid, thiophanate and ziram) from foetal development until 8 weeks old. Female offspring presented with decreased body weight at weaning, which was maintained at 8 weeks old. This was accompanied by an abnormal ovarian ultrastructure, a drastic decrease in the number of corpora lutea and progesterone levels and an increase in ovary cell proliferation. In conclusion, this study shows that this pesticide mixture that can be commonly found in fruits in Europe, causing endocrine disruption in female mice with pre- and postnatal exposure by disturbing folliculogenesis, mainly in the luteinisation process.

Published
2022
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5. Translation and codon usage regulate Argonaute slicer activity to trigger small RNA biogenesis

Author

Germano Cecere, Meetali Singh, Eric Cornes, Blaise Li, Piergiuseppe Quarato, Loan Bourdon, Florent Dingli, Damarys Loew, Simone Procaccia, Mécanismes de l'Hérédité épigénétique / Mechanisms of epigenetic inheritance, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Collège doctoral [Sorbonne universités], Sorbonne Université (SU), Laboratoire de Spectrométrie de Masse Protéomique, Institut Curie [Paris], University of Trento [Trento], Some strains were provided by the CGC, funded by the NIH Office of Research Infrastructure Programs (P40 OD010440). This project has received funding from the Institut Pasteur, the CNRS, and the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program under grant agreement No. ERC-StG- 679243. M.S. and E.C. were supported by the Pasteur-Roux-Cantarini Postdoctoral Fellowship program. P.Q. was supported by Ligue Nationale Contre le Cancer (SFB19032). F.D. and D.L. have received funding from Région Ile-de-France and Fondation pour la Recherche Médicale grants to support this study., We would like to thank all the members of the Cecere laboratory, Manish Grover, Sudarshan Gadadhar, and Angela Anderson (Life Science Editors), for the helpful discussions on the paper. We thank Micheline Fromont for her help to set up Ribosome profiling. We thank Celine Didier for technical assistance. Sequencing was performed at the Biomics centre at the Institut Pasteur. We thank the Heng-Chi Lee lab, Miska lab, Desai lab, Strome lab, Mello lab, Updike lab, and Kennedy lab for sharing strains and reagents., European Project: 679243,H2020,ERC-2015-STG,RNAEPIGEN(2016), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), and Collège Doctoral

Subjects
Science, Small RNAs, chemical and pharmacologic phenomena, RNA-Dependent RNA Polymerase, RNA decay, Ribosome, Catalysis, Article, Cytosol, Oogonia, Protein Biosynthesis, RNAi, Argonaute Proteins, Mutation, Animals, RNA Interference, RNA, Messenger, RNA, Small Interfering, Caenorhabditis elegans, Caenorhabditis elegans Proteins, Codon Usage, Ribosomes, [SDV.BDD]Life Sciences [q-bio]/Development Biology
Abstract

In the Caenorhabditis elegans germline, thousands of mRNAs are concomitantly expressed with antisense 22G-RNAs, which are loaded into the Argonaute CSR-1. Despite their essential functions for animal fertility and embryonic development, how CSR-1 22G-RNAs are produced remains unknown. Here, we show that CSR-1 slicer activity is primarily involved in triggering the synthesis of small RNAs on the coding sequences of germline mRNAs and post-transcriptionally regulates a fraction of targets. CSR-1-cleaved mRNAs prime the RNA-dependent RNA polymerase, EGO-1, to synthesize 22G-RNAs in phase with translating ribosomes, in contrast to other 22G-RNAs mostly synthesized in germ granules. Moreover, codon optimality and efficient translation antagonize CSR-1 slicing and 22G-RNAs biogenesis. We propose that codon usage differences encoded into mRNA sequences might be a conserved strategy in eukaryotes to regulate small RNA biogenesis and Argonaute targeting., 22G-RNAs are single-stranded antisense small RNAs that are expressed in C. elegans germline. Here the authors show that CSR-1 dependent 22G-RNAs are produced in the cytosol on mRNAs actively engaged in translation and that codon usage of an mRNA regulates the biogenesis of CSR-1 dependent 22G-RNAs.

Published
2021

6. Halving food-related greenhouse gas emissions can be achieved by redistributing meat consumption: progressive optimization Results of the NutriNet-Santé cohort

Author

Julia Baudry, Denis Lairon, Alison Dussiot, Philippe Pointereau, Brigitte Langevin, Benjamin Allès, Pauline Rebouillat, Emmanuelle Kesse-Guyot, Mathilde Touvier, Joséphine Brunin, Serge Hercberg, François Mariotti, Hélène Fouillet, 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), Physiologie de la Nutrition et du Comportement Alimentaire (PNCA (UMR 0914)), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), SOLAGRO, Solagro, Agence de l'Environnement et de la Maîtrise de l'Energie (ADEME), Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Association Solagro (Solagro), The NutriNet-Sante study is funded by FrenchMinistry of Health and Social Affairs, Sante Publique France, Institut National de la Sante et de la Recherche Medicale, Institut National de la Recherche Agronomique, Conservatoire National des Arts et Metiers, and Sorbonne Paris Nord University. 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). The funders had no role in the study design, data collection, analysis, interpretation of data, preparation of the manuscript, and decision to submit the paper., 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), Kesse-guyot, Emmanuelle, and 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

Subjects
Adult, Male, Meat, Environmental Engineering, 010504 meteorology & atmospheric sciences, Animal food, 010501 environmental sciences, 01 natural sciences, Food Supply, Nutrition Policy, Greenhouse Gases, Nutrient, Animal science, Ruminant, Animals, Humans, Environmental Chemistry, Waste Management and Disposal, Aged, 0105 earth and related environmental sciences, 2. Zero hunger, Consumption (economics), [SDV.EE]Life Sciences [q-bio]/Ecology, environment, biology, business.industry, Intensive farming, greenhouse gas emissions, Middle Aged, biology.organism_classification, co-product tradeoffs, Pollution, Diet, [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, [SDV.EE] Life Sciences [q-bio]/Ecology, environment, diet sustainability, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 13. Climate action, Greenhouse gas, Cohort, Food processing, Environmental science, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, optimization modelling, Energy Intake, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract

Background Diet-related greenhouse gas emissions (GHGe) mainly comes from animal-sourced foods. As progressive changes are more acceptable for a sustainable food transition, we aimed to identify nutritionally adequate and culturally acceptable optimized diets ensuring a gradual reduction in GHGe, using observed diet from a large sample of French adults, while considering the mode of food production (organic vs conventional farming) and the co-production link between milk and beef. Material and method Based on the consumption of 257 organic and conventional foods among 29,413 participants (75% women, age: 53.5 ± 14.0y) of the NutriNet-Sante study, we modelled optimal diets according to GHGe reduction scenarios in 5% steps, from 0 to 50% with nutritional, acceptability, and coproduct constraints, for men, premenopausal and menopausal women separately. Results Gradual GHGe decrease under these constraints led to optimal diets with an overall decrease in animal foods, with marked reductions in dairy products (up to −83%), together with a stable but largely redistributed meat consumption in favor of poultry (up to +182%) and pork (up to +46%) and at the expense of ruminant meat (down to −92%). Amounts of legumes increases dramatically (up to +238%). The greater the reduction in diet-related GHGe, the lower the cumulative energy demand (about −25%) and land use (about −43%). The proportion of organic food increased from ~30% in the observed diets to ~70% in the optimized diets. Conclusion Our results suggest that meeting both nutrient reference value and environmental objectives of up to 50% GHGe reduction requires the reduction of animal foods together with important substitutions between animal food groups, which result in drastic reductions in beef and dairy products. Further research is required to explore alignment with long-term health value and conflict with acceptability, in particular for even greater GHGe reductions.

Published
2021

7. A review of current treatment strategies for infective endocarditis

Author

Ines Lakbar, David Luque Paz, Pierre Tattevin, CHU Pontchaillou [Rennes], CHU Toulouse [Toulouse], ARN régulateurs bactériens et médecine (BRM), 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 ), This paper was not funded., Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and 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 )

Subjects
0301 basic medicine, Microbiology (medical), Oral treatment, medicine.medical_specialty, Prosthesis-Related Infections, Time Factors, empirical treatment, medicine.drug_class, [SDV]Life Sciences [q-bio], 030106 microbiology, Antibiotics, Heart Valve Diseases, review, Microbiology, antibiotics, 03 medical and health sciences, 0302 clinical medicine, enterococci, Virology, medicine, Endocarditis, Animals, Humans, 030212 general & internal medicine, Intensive care medicine, staphylococci, treatment, business.industry, HACEK, oral treatment, Endocarditis, Bacterial, medicine.disease, 3. Good health, Anti-Bacterial Agents, Empirical treatment, Infectious Diseases, streptococci, Infective endocarditis, Heart Valve Prosthesis, Treatment strategy, business
Abstract

International audience; Introduction Infective endocarditis is one of the most difficult-to-treat infectious diseases. Areas covered We restricted this review to the anti-infective treatment of the main bacteria responsible for infective endocarditis, i.e. staphylococci, streptococci, enterococci, and Gram-negative bacilli, including HACEK. Specific topics of major interest in treatment strategy are covered as well, including empirical treatment, oral switch, and treatment duration. We searched in the MEDLINE database to identify relevant studies, trials, reviews, or meta-analyses until May 2020. Expert opinion The use of aminoglycosides for the treatment of endocarditis has been dramatically reduced over the last 20 years. It should be administered once daily, and no longer than 2 weeks. For staphylococcal endocarditis, recent data reinforced the role of anti-staphylococcal penicillins, for methicillin-susceptible isolates (alternative, cefazolin), and vancomycin for methicillin-resistant isolates (alternative, daptomycin). For staphylococcal prosthetic-valve endocarditis, these treatments will be reinforced by the addition of gentamicin during the first 2 weeks, and rifampin throughout the whole treatment duration, i.e. 6 weeks. The optimal duration of antibacterial treatment is 4 weeks for most native valve endocarditis, and 6 weeks for prosthetic-valve endocarditis. The oral switch is safe in patients stabilized after the initial intravenous course.

Published
2021

8. Grammatical Gender and Anthropomorphism: 'It' Depends on the Language

Author

Alican Mecit, L. J. Shrum, Tina M. Lowrey, Ecole des Hautes Etudes Commerciales (HEC Paris), and HEC Paris Research Paper Series

Subjects
Male, Sociology and Political Science, Social Psychology, Turkish, media_common.quotation_subject, 050109 social psychology, Psycholinguistics, 050105 experimental psychology, Leverage (negotiation), Perception, Animals, Humans, 0501 psychology and cognitive sciences, psycholinguistics, Language, media_common, Grammatical gender, 05 social sciences, anthropomorphism, Gender Identity, Linguistics, language.human_language, Antecedent (grammar), language, [SHS.GESTION]Humanities and Social Sciences/Business administration, Female, Psychology, Natural language
Abstract

Consumers often anthropomorphize non-human entities. In this research, we investigate a novel antecedent of anthropomorphism: language. Some languages (e.g., English) make a grammatical distinction between humans (he, she) and non-humans (it), whereas other languages (e.g., French) do not (all objects are gender-marked). We propose that such grammatical structures of languages influence the way individuals mentally represent non-human entities, and as a result, their generalized tendencies to anthropomorphize such entities. Across 10 studies, we provide evidence that speakers of languages that do not grammatically distinguish between humans and non-humans (it-less languages) anthropomorphize more than do speakers of languages that do make this distinction (non-it-less languages). We demonstrate the effects across natural languages (French, Turkish, English) and by manipulating grammatical gender. We show that the effects are observable in naturally occurring consumer contexts (e.g., secondary sales data), and that gender-marking in it-less languages influences consumers’ interactions with brands, even though the gender-markings are semantically arbitrary, and that these effects occur nonconsciously. Our findings have implications for the broader debate on the extent to which language influences thought, and also suggest ways in which managers can leverage nonconscious grammatical anthropomorphism to influence consumer perceptions, attitudes, and behavior.

Published
2020

9. The interplay between innate lymphoid cells and T cells

Author

Gayetri Ramachandran, Rachel Golub, Marie Cherrier, Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut Necker Enfants-Malades (INEM - UM 111 (UMR 8253 / U1151)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Lymphocytes et Immunité - Lymphocytes and Immunity, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), M.C. is supported by INSERM and Association François Aupetit dedicated to patients suffering from IBD. R.G. work is supported by Institut Pasteur, Institut National de la Santé et de la Recherche Médicale, Université de Paris, and ANR project NASHILCCD8 (#18-CE15-0024-01)., We thank Serge van de Pavert for critical discussions and for review of the paper., ANR-18-CE15-0024,NASHILCCD8,Contribution des ILC et des cellules T CD8 à la stéatose hépatique non alcoolique et à sa progression vers l'hépatocarcinome.(2018), Vougny, Marie-Christine, APPEL À PROJETS GÉNÉRIQUE 2018 - Contribution des ILC et des cellules T CD8 à la stéatose hépatique non alcoolique et à sa progression vers l'hépatocarcinome. - - NASHILCCD82018 - ANR-18-CE15-0024 - AAPG2018 - VALID, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), and Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)

Subjects
0301 basic medicine, Cell type, [SDV.IMM] Life Sciences [q-bio]/Immunology, Immunology, Context (language use), Cell Communication, Biology, Gut flora, Adaptive Immunity, Lymphocyte Activation, Substrate Specificity, Immunomodulation, 03 medical and health sciences, 0302 clinical medicine, Immune system, T-Lymphocyte Subsets, Immunology and Allergy, Animals, Humans, skin and connective tissue diseases, Immunity, Cellular, Innate lymphoid cell, Cell Differentiation, Acquired immune system, biology.organism_classification, Immunity, Innate, body regions, 030104 developmental biology, Gene Expression Regulation, Host-Pathogen Interactions, [SDV.IMM]Life Sciences [q-bio]/Immunology, Neuroscience, Immunologic Memory, Function (biology), Homeostasis, Biomarkers, 030215 immunology, Signal Transduction
Abstract

International audience; ILCs and T cells are closely related functionally but they significantly differ in their ability to circulate, expand, and renew. Cooperation and reciprocal functional regulation suggest that these cell types are more complementary than simply redundant during immune responses. How ILCs shape T-cell responses is strongly dependent on the tissue and inflammatory context. Likewise, indirect regulation of ILCs by adaptive immunity is induced by environmental cues such as the gut microbiota. Here, we review shared requirements for the development and function of both cell types and divergences in the orchestration of prototypic immune functions. We discuss the diversity of functional interactions between T cells and ILCs during homeostasis and immune responses. Identifying the location and the nature of the tissue microenvironment in which these interactions are taking place may uncover the remaining mysteries of their close encounters.

Published
2020

10. The nicotinic receptor alpha5 coding polymorphism rs16969968 as a major target in disease: Functional dissection and remaining challenges

Author

Uwe Maskos, Neurobiologie intégrative des Systèmes cholinergiques / Integrative Neurobiology of Cholinergic Systems (NISC), Sorbonne Université (SU)-Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), he author has received funding to carry out the work of his laboratory described in the Review article, as indicated in the published papers. No funding has been received that is directly relevant to this Review article. The author has no conflict of interest to declare., and Institut Pasteur [Paris] (IP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, human genetics, Single-nucleotide polymorphism, Locus (genetics), Genome-wide association study, Disease, Receptors, Nicotinic, Biology, Bioinformatics, Polymorphism, Single Nucleotide, Biochemistry, nicotine addiction, drug discovery, 03 medical and health sciences, Cellular and Molecular Neuroscience, [SCCO]Cognitive science, 0302 clinical medicine, single nucleotide polymorphism, Animals, Humans, nicotinic acetylcholine receptor, Genetic association, [SCCO.NEUR]Cognitive science/Neuroscience, Human genetics, 3. Good health, schizophrenia, Nicotinic acetylcholine receptor, 030104 developmental biology, Nicotinic agonist, positive allosteric modulator, Genome-wide Association Studies, 030217 neurology & neurosurgery
Abstract

International audience; Nicotinic acetylcholine receptors (nAChRs) are major signalling molecules in the central and peripheral nervous system. Over the last decade, they have been linked to a number of major human psychiatric and neurological conditions, like smoking, schizophrenia, Alzheimer's disease and many others. Human Genome-Wide Association Studies (GWAS) have robustly identified genetic alterations at a locus of chromosome 15q to several of these diseases. In this review, we discuss a major coding polymorphism in the alpha5 subunit, referred to as α5SNP, and its functional dissection in vitro and in vivo. Its presence at high frequency in many human populations lends itself to pharmaceutical intervention in the context of 'positive allosteric modulators' (PAMs). We will present the prospects of this novel treatment, and the remaining challenges to identify suitable molecules.

Published
2020

11. Consumption of Fish and ω-3 Fatty Acids and Cancer Risk: An Umbrella Review of Meta-Analyses of Observational Studies

Author

Hans Oh, Mingyang Song, Jae Il Shin, Ai Koyanagi, Louis Jacob, Andreas Kronbichler, Gaeun Kim, Michael Eisenhut, Eun Kyoung Choi, Sun Jae Jung, Lin Yang, Marco Solmi, Gwang Hun Jeong, Eunyoung Jung, Brendon Stubbs, Keum Hwa Lee, Eunyoung Cho, Joaquim Radua, Edward Giovannucci, NaNa Keum, Hyo Jin Seong, Nicola Veronese, Hyunbong Park, Lee Smith, Gabriele Gamerith, Giuseppe Grosso, Trevor Thompson, Elena Dragioti, Sarah E Jackson, Leandro Fórnias Machado de Rezende, Shuji Ogino, Jong Yeob Kim, Hans van Vliet, Sung Hwi Hong, Université de Versailles Saint-Quentin-en-Yvelines - UFR Sciences de la santé Simone Veil (UVSQ Santé), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), South London and Maudsley NHS Foundation Trust National Institute for Health Research, NIHR NIHR Collaboration for Leadership in Applied Health Research and Care South London National Institutes of Health, NIH: R35 CA197735 Maudsley Charity King’s College London National Institutes of Health, NIH: R35 CA197735, KHL, HJS, GK, GHJ, and JYK contributed equally to this work. The authors report no funding received for this study. Author Disclosures: The authors report no conflicts of interest. BS is supported by a Clinical Lectureship (ICA-CL-2017-03-001) jointly funded by Health Education England (HEE) and the National Institute for Health Research (NIHR), is in part funded by the NIHR Biomedical Research Centre at South London and Maudsley NHS Foundation Trust, and is also supported by the Maudsley Charity, King’s College London, and the NIHR South London Collaboration for Leadership in Applied Health Research and Care (CLAHRC) funding. The time effort of SO was in part supported by US National Institutes of Health grant R35 CA197735. This paper presents independent research. The views expressed in this publication are those of the authors and not necessarily those of the acknowledged institutions. Address correspondence to JIS (e-mail: shinji@yuhs.ac) or EKC (e-mail: ekchoi@yuhs.ac). Supplemental Table 1 is available from the 'Supplementary data'link in the online posting of the article and from the same link in the online table of contents at https://academic.oup.com/advances. Abbreviation used: ALA, α-linolenic acid, AMSTAR2, A Measurement Tool to Assess Systematic Reviews 2, CUP, Continuous Update Project, DPA, docosapentaenoic acid, GRADE, Grading of Recommendations Assessment, Development and Evaluation, HCC, hepatocellular carcinoma, NA, not assessable, PI, prediction interval, PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses, WCRF/AICR, Word Cancer Research Fund/American Institute for Cancer Research., The time effort of SO was in part supported by US National Institutes of Health grant R35 CA197735., Lee, K.H., Seong, H.J., Kim, G., Jeong, G.H., Kim, J.Y., Park, H., Jung, E., Kronbichler, A., Eisenhut, M., Stubbs, B., Solmi, M., Koyanagi, A., Hong, S.H., Dragioti, E., De Rezende, L.F.M., Jacob, L., Keum, N., Van Der Vliet, H.J., Cho, E., Veronese, N., Grosso, G., Ogino, S., Song, M., Radua, J., Jung, S.J., Thompson, T., Jackson, S.E., Smith, L., Yang, L., Oh, H., Choi, E.K., Shin, J.I., Giovannucci, E.L., and Gamerith, G.

Subjects
Male, Risk, Oncology, medicine.medical_specialty, [SDV]Life Sciences [q-bio], BF, Medicine (miscellaneous), Review, Cohort Studies, 03 medical and health sciences, Prostate cancer, 0302 clinical medicine, Breast cancer, ω-3 fatty acid, Meta-Analysis as Topic, Neoplasms, Internal medicine, Fatty Acids, Omega-3, medicine, Animals, Humans, cancer, 030212 general & internal medicine, ω-3 fatty acid, fish, cancer, umbrella review, meta-analysis, chemistry.chemical_classification, fish, Nutrition and Dietetics, umbrella review, business.industry, Endometrial cancer, Fishes, Fatty acid, Cancer, medicine.disease, R1, 3. Good health, meta-analysis, Observational Studies as Topic, chemistry, Case-Control Studies, 030220 oncology & carcinogenesis, Meta-analysis, Female, Skin cancer, business, Liver cancer, Food Science
Abstract

Multiple studies have suggested that ω-3 fatty acid intake may have a protective effect on cancer risk; however, its true association with cancer risk remains controversial. We performed an umbrella review of meta-analyses to summarize and evaluate the evidence for the association between ω-3 fatty acid intake and cancer outcomes. We searched PubMed, Embase, and the Cochrane Database of Systematic Reviews from inception to December 1, 2018. We included meta-analyses of observational studies that examined associations between intake of fish or ω-3 fatty acid and cancer risk (gastrointestinal, liver, breast, gynecologic, prostate, brain, lung, and skin) and determined the level of evidence of associations. In addition, we appraised the quality of the evidence of significant meta-analyses by using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. We initially screened 598 articles, and 15 articles, including 57 meta-analyses, were eligible. Among 57 meta-analyses, 15 reported statistically significant results. We found that 12 meta-analyses showed weak evidence of an association between ω-3 fatty acid intake and risk of the following types of cancer: liver cancer (n = 4 of 6), breast cancer (n = 3 of 14), prostate cancer (n = 3 of 11), and brain tumor (n = 2 of 2). In the other 3 meta-analyses, studies of endometrial cancer and skin cancer, there were no assessable data for determining the evidence levels. No meta-analysis showed convincing, highly suggestive, or suggestive evidence of an association. In the sensitivity analysis of meta-analyses by study design, we found weak associations between ω-3 fatty acid intake and breast cancer risk in cohort studies, but no statistically significant association in case-control studies. However, the opposite results were found in case of brain tumor risk. Although ω-3 fatty acids have been studied in several meta-analyses with regard to a wide range of cancer outcomes, only weak associations were identified in some cancer types, with several limitations. Considering the nonsignificant or weak evidence level, clinicians and researchers should cautiously interpret reported associations between ω-3 fatty acid consumption and cancer risks. Copyright © 2020 The Author(s) on behalf of the American Society for Nutrition.

Published
2020

12. Potential of Aedes albopictus and Aedes aegypti (Diptera: Culicidae) to transmit yellow fever virus in urban areas in Central Africa

Author

Basile Kamgang, Aurelie P. Yougang, Theodel A. Wilson-Bahun, Armel N. Tedjou, Charles S. Wondji, Laurence Mousson, Anna-Bella Failloux, Marie Vazeille, Centre for Research in Infectious Diseases [Yaoundé] (CRID), Arbovirus et Insectes Vecteurs - Arboviruses and Insect Vectors, Institut Pasteur [Paris] (IP), Université de Yaoundé I, University Marien Ngouabi of Brazzaville (umng), Liverpool School of Tropical Medicine (LSTM), This study was supported by a Wellcome Trust Training Fellowship in Public Health and Tropical Medicine [grant number 204862/Z/16/Z] awarded to BK., We would like to thank the populations of different collection sites for their collaboration during the field works. BK, CSW and ABF designed the experiments. BK performed the research. MV and LM provided a technical help. ANT, APY, TAWB helped in mosquito collections, BK, CSW and ABF wrote the paper with contribution from all other authors., and Institut Pasteur [Paris]

Subjects
0301 basic medicine, medicine.medical_specialty, Aedes albopictus, Epidemiology, 030106 microbiology, Immunology, wa_395, Mosquito Vectors, Aedes aegypti, Microbiology, Article, law.invention, 03 medical and health sciences, Aedes, law, Virology, Yellow Fever, Drug Discovery, parasitic diseases, medicine, Animals, Humans, qx_525, Africa, Central, Socioeconomics, yellow fever virus, vector competence, Central Africa, biology, Public health, Yellow fever, Outbreak, General Medicine, biology.organism_classification, medicine.disease, wc_530, 3. Good health, 030104 developmental biology, Infectious Diseases, Geography, Transmission (mechanics), Vector (epidemiology), [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, Parasitology
Abstract

International audience; Yellow Fever (YF) remains a major public health issue in Sub-Saharan Africa and South America, despite the availability of an effective vaccine. In Africa, most YF outbreaks are reported in West Africa. However, urban outbreaks occurred in 2016 in both Angola and the Democratic Republic of Congo (DRC), and imported cases were reported in Chinese workers coming back from Africa. In Central Africa, Cameroon and the Republic of Congo host a high proportion of non-vaccinated populations increasing the risk of urban outbreaks. The main vector is Aedes aegypti and possibly, Aedes albopictus, both being anthropophilic and domestic mosquitoes. Here, we provide evidence that both Ae. aegypti and Ae. albopictus in Cameroon and the Republic of Congo are able to transmit Yellow fever virus (YFV) with higher rates of infection, dissemination, and transmission for Ae. aegypti. We conclude that the potential of both Aedes species to transmit YFV could increase the risk of urban YF transmission and urge public health authorities to intensify their efforts to control domestic vectors, and extend vaccine coverage to prevent major YFV outbreak.

Published
2019

13. Quantifying model evidence for yellow fever transmission routes in Africa

Author

Katy A. M. Gaythorpe, Laurence Cibrelus, Tini Garske, Kévin Jean, Imperial College London, Laboratoire Modélisation, épidémiologie et surveillance des risques sanitaires (MESuRS), Conservatoire National des Arts et Métiers [CNAM] (CNAM), Pasteur-Cnam Risques infectieux et émergents (PACRI), Institut Pasteur [Paris]-Conservatoire National des Arts et Métiers [CNAM] (CNAM), World Health Organisation (WHO), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Funding:This work was carried out as part of the Vaccine Impact Modelling Consortium (www.vaccineimpact.org),but the views expressed are those of the authors and not necessarily those of the Consortium or its funders.The funders were given the opportunity to review this paper prior to publication,but the final decision on the content of the publication was taken by the authors.We acknowledge joint Centre funding from the UK Medical Research Council and Department for International Development. The research leading to these results has received funding from the Bill & Melinda Gates foundation (OPP1117543,OPP1157270 http://www.gatesfoundation.org/)and from the Medical Research Council (MR/R015600/1https://mrc.ukri.org/)., 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), and Institut Pasteur [Paris] (IP)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)

Subjects
0301 basic medicine, Viral Diseases, Epidemiology, Force of infection, Statics, Pathology and Laboratory Medicine, law.invention, Geographical Locations, Bayes' theorem, 0302 clinical medicine, law, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Aedes, Statistics, Medicine and Health Sciences, Public and Occupational Health, Biology (General), Ecology, Physics, Yellow fever, Linear model, Classical Mechanics, Vaccination and Immunization, Geography, Transmission (mechanics), Infectious Diseases, Serology, Computational Theory and Mathematics, INFECTIONS, Modeling and Simulation, Physical Sciences, Yellow fever virus, Life Sciences & Biomedicine, Research Article, Generalized linear model, Biochemistry & Molecular Biology, Bioinformatics, QH301-705.5, Immunology, Bayesian inference, Models, Biological, Biochemical Research Methods, BAYESIAN MODEL, Infectious Disease Epidemiology, 03 medical and health sciences, Cellular and Molecular Neuroscience, Yellow Fever, Genetics, medicine, Animals, Humans, Molecular Biology, 01 Mathematical Sciences, Ecology, Evolution, Behavior and Systematics, Estimation, Science & Technology, Models, Statistical, Biology and Life Sciences, Computational Biology, Bayes Theorem, 06 Biological Sciences, medicine.disease, 030104 developmental biology, People and Places, Africa, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Mathematical & Computational Biology, 08 Information and Computing Sciences, Preventive Medicine, 030217 neurology & neurosurgery
Abstract

Yellow fever is a vector-borne disease endemic in tropical regions of Africa, where 90% of the global burden occurs, and Latin America. It is notoriously under-reported with uncertainty arising from a complex transmission cycle including a sylvatic reservoir and non-specific symptom set. Resulting estimates of burden, particularly in Africa, are highly uncertain. We examine two established models of yellow fever transmission within a Bayesian model averaging framework in order to assess the relative evidence for each model’s assumptions and to highlight possible data gaps. Our models assume contrasting scenarios of the yellow fever transmission cycle in Africa. The first takes the force of infection in each province to be static across the observation period; this is synonymous with a constant infection pressure from the sylvatic reservoir. The second model assumes the majority of transmission results from the urban cycle; in this case, the force of infection is dynamic and defined through a fixed value of R0 in each province. Both models are coupled to a generalised linear model of yellow fever occurrence which uses environmental covariates to allow us to estimate transmission intensity in areas where data is sparse. We compare these contrasting descriptions of transmission through a Bayesian framework and trans-dimensional Markov chain Monte Carlo sampling in order to assess each model’s evidence given the range of uncertainty in parameter values. The resulting estimates allow us to produce Bayesian model averaged predictions of yellow fever burden across the African endemic region. We find strong support for the static force of infection model which suggests a higher proportion of yellow fever transmission occurs as a result of infection from an external source such as the sylvatic reservoir. However, the model comparison highlights key data gaps in serological surveys across the African endemic region. As such, conclusions concerning the most prevalent transmission routes for yellow fever will be limited by the sparsity of data which is particularly evident in the areas with highest predicted transmission intensity. Our model and estimation approach provides a robust framework for model comparison and predicting yellow fever burden in Africa. However, key data gaps increase uncertainty surrounding estimates of model parameters and evidence. As more mathematical models are developed to address new research questions, it is increasingly important to compare them with established modelling approaches to highlight uncertainty in structures and data., Author summary Yellow fever (YF) is notoriously under reported due to non-specific symptom spectrum and the true burden is highly uncertain as a result of a complex transmission cycle. As such, estimates surrounding YF burden are highly uncertain and the mechanisms behind transmission are often unclear. We assess these mechanisms and the resulting uncertainty by estimating two existing models of YF transmission within a product space framework. This allows us to produce updated estimates of transmission intensity and to compare the relative support for each model given the data. We find strong support for a model assuming a static force of infection, approximating the constant infection pressure from the sylvatic reservoir of YF. We also highlight areas where data is sparse, often the same areas estimated to have especially high transmission intensity. This is the first robust multi-model approach to applied YF modelling and provides a framework that could be extended to other disease models.

Published
2019

14. Spatial frequency domain imaging in 2019: principles, applications, and perspectives

Author

Gioux, Sylvain, Mazhar, Amaan, Cuccia, David, Laboratoire des sciences de l'ingénieur, de l'informatique et de l'imagerie (ICube), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche en Informatique et en Automatique (Inria)-Les Hôpitaux Universitaires de Strasbourg (HUS)-Centre National de la Recherche Scientifique (CNRS)-Matériaux et Nanosciences Grand-Est (MNGE), Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Réseau nanophotonique et optique, Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Modulim [Irvine, CA, USA], Some of the work presented in this paper is supported by the European Research Council (ERC) under the European Union’s Horizon 2020 Research And Innovation Program under Grant Agreement No. 715737 (QuantSURG, S.G.), France Life Imaging WP3 (S.G.), the French program 'Investissement d’Avenir' run by the 'Agence Nationale de la Recherche' under Grant Agreement No. ANR-11-INBS-006 (S.G.), and the University of Strasbourg IdEx (S.G.)., ANR-11-INBS-0006,FLI,France Life Imaging(2011), Gioux, Sylvain, Infrastructures - France Life Imaging - - FLI2011 - ANR-11-INBS-0006 - INBS - VALID, Institut National des Sciences Appliquées - Strasbourg (INSA Strasbourg), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Réseau nanophotonique et optique, Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Matériaux et nanosciences d'Alsace (FMNGE), and Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Université de Haute-Alsace (UHA) Mulhouse - Colmar (Université de Haute-Alsace (UHA))-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Paper, [SPI.OPTI] Engineering Sciences [physics]/Optics / Photonic, Swine, Optical Imaging, Equipment Design, Hand, diffuse optical imaging, spatial frequency domain imaging, Surgery, Computer-Assisted, quantitative imaging, Special Section on Spatial Frequency Domain Imaging, [SPI.OPTI]Engineering Sciences [physics]/Optics / Photonic, Image Processing, Computer-Assisted, Animals, Humans, Intestine, Large, Burns
Abstract

International audience; Spatial frequency domain imaging (SFDI) has witnessed very rapid growth over the last decade, owing to its unique capabilities for imaging optical properties and chromophores over a large field-of-view and in a rapid manner. We provide a comprehensive review of the principles of this imaging method as of 2019, review the modeling of light propagation in this domain, describe acquisition methods, provide an understanding of the various implementations and their practical limitations, and finally review applications that have been published in the literature. Importantly, we also introduce a group effort by several key actors in the field for the dissemination of SFDI, including publications, advice in hardware and implementations, and processing code, all freely available online.

Published
2019

15. Real-time analysis of the behaviour of groups of mice via a depth-sensing camera and machine learning

Author

Philippe Faure, Jean-Christophe Olivo-Marin, Fabrice de Chaumont, Nicolas Torquet, Albane Imbert, Stephane Dallongeville, Anne-Marie Le Sourd, Thomas Bourgeron, Elodie Ey, Thierry Legou, Thibault Lagache, Analyse d'images biologiques - Biological Image Analysis (BIA), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Génétique humaine et fonctions cognitives - Human Genetics and Cognitive Functions (GHFC (UMR_3571 / U-Pasteur_1)), Institut Pasteur [Paris]-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Neurosciences Paris Seine (NPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche et Innovation Technologique (CITECH), Institut Pasteur [Paris], Laboratoire Parole et Langage (LPL), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), This work was partially funded by the Institut Pasteur, the Bettencourt-Schueller Foundation, the Cognacq–Jay Foundation, the Conny–Maeva Foundation, the ERANET–NEURON SYNPATHY program, the Agence Nationale de la Recherche through grant number ANR-10-LABX-62-IBEID, France-BioImaging infrastructure through grant number ANR-10-INBS-04 and the INCEPTION program through grant number ANR-16-CONV-0005, the Centre National de la Recherche Scientifique, the University Paris Diderot, the BioPsy Labex, the Institut National du Cancer through grant number TABAC-16–022, the Foundation for Medical Research (Equipe DEQ20130326488), the Innovative Medicines Initiative Joint Undertaking through grant agreement number 115300, resources of which are composed of financial contributions from the European Union’s Seventh Framework Program (FP7/2007–2013) and EFPIA companies in kind contribution., The authors thank Y. Archambeau and P. Ollivon at the workshop of the Institut Pasteur for building the first 12 setups and advising on hardware, W. Meiniel for the mathematical proof for decisions of head/tail probability, Microsoft France for their technical support, P. Spinicelli for optical engineering and reading of the paper, R. Marée for machine learning support, B. König for advice and reading of biological experiments, J. N. Crawley for reading and providing comments on the manuscript, A. Barmpoutis for providing us with the early Kinect 2 driver and support, N. Chenouard for driving the use of the machine learning solution, P. Dugast for drawing the mice in the different behavioural events, A. Engelberg for checking the English, S. Wagner and R. Accardi for RFID advice, M. Marim for website development, and X. Montagutelli and M. Bérard for animal facility support., Analyse d'images biologiques - BioImage Analysis (AIQ), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Institut Pasteur [Paris], Neuroscience Paris Seine (NPS), Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), ANR-16-CONV-0005,INCEPTION,Institut Convergences pour l'étude de l'Emergence des Pathologies au Travers des Individus et des populatiONs(2016), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
0301 basic medicine, Male, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Biomedical Engineering, Video Recording, Medicine (miscellaneous), Bioengineering, Nerve Tissue Proteins, Mouse tracking, Biology, Machine learning, computer.software_genre, Machine Learning, 03 medical and health sciences, Mice, 0302 clinical medicine, [INFO.INFO-TS]Computer Science [cs]/Signal and Image Processing, Animals, Autistic Disorder, Real time analysis, Social Behavior, Mice, Knockout, Behavior, Animal, business.industry, Microfilament Proteins, Computer Science Applications, Disease Models, Animal, 030104 developmental biology, Phenotype, Mutation, Identification (biology), Female, Artificial intelligence, business, computer, 030217 neurology & neurosurgery, Biotechnology, Behavioral Research
Abstract

Preclinical studies of psychiatric disorders use animal models to investigate the impact of environmental factors or genetic mutations on complex traits such as decision-making and social interactions. Here, we introduce a method for the real-time analysis of the behaviour of mice housed in groups of up to four over several days and in enriched environments. The method combines computer vision through a depth-sensing infrared camera, machine learning for animal and posture identification, and radio-frequency identification to monitor the quality of mouse tracking. It tracks multiple mice accurately, extracts a list of behavioural traits of both individuals and the groups of mice, and provides a phenotypic profile for each animal. We used the method to study the impact of Shank2 and Shank3 gene mutations—mutations that are associated with autism—on mouse behaviour. Characterization and integration of data from the behavioural profiles of Shank2 and Shank3 mutant female mice revealed their distinctive activity levels and involvement in complex social interactions. A method that combines a depth-sensing camera and machine learning can track the movements of up to four mice in real time and for several days, extracting both individual and group behavioural traits.

Published
2019

17. Current and future distribution of Aedes aegypti and Aedes albopictus (Diptera : Culicidae) in WHO Eastern Mediterranean Region

Author

Johannes Charlier, Ward Bryssinckx, Valérie De Waele, Frédéric Simard, Evans Buliva, Abdulhafid Hussain, Nhu Nguyen Tran Minh, Muhammad Mukhtar, David Roiz, Nabil Haddad, Ali Bouattour, Guy Hendrickx, Els Ducheyne, Osama Mahmoud, Mamunur Rahman Malik, Avia-GIS [Zoersel], WHO - Regional Office for the Eastern Mediterranean [Cairo, Egypt] (EMRO), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Université Libanaise, Diversity, ecology, evolution & Adaptation of arthropod vectors (MIVEGEC-DEEVA), Evolution des Systèmes Vectoriels (ESV), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Ministry of Health Oman, Directorate of Malaria Control [Islamabad] (DoMC), Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP), Ministry of Health and Human Services [Somalia], Vector Control Group (MIVEGEC-VCG), This work was supported by the WHO Regional Office for the Eastern Mediterranean. The work was supported partially by the project InvaCosts (ANR-14-CE02-0021-01). Field work in Lebanon was supported by the WHO National Bureau (LEB1409860)., We thank the numerous entomologists and health officers of the EMR who shared data with the WHO Regional Office for the Eastern Mediterranean. Ms. Barwa and Dr. Zayed are gratefully acknowledged for their technical assistance. We gratefully acknowledge the valuable input of the anonymous reviewers on the first version of this paper., ANR-14-CE02-0021,InvaCosts,Insectes envahissants et leurs couts pour la biodiversité, l'économie et la santé humaine(2014), and Regional Office for the Eastern Mediterranean [Cairo] (EMRO)

Subjects
0301 basic medicine, Species distribution, Distribution (economics), Geographic Mapping, Distribution, medicine.disease_cause, Population density, MESH: Mosquito Vectors, MESH: Yellow Fever/diagnosis, Dengue fever, Dengue, MESH: Aedes, 0302 clinical medicine, Aedes aegypti, Aedes, MESH: Animals, Chikungunya, MESH: Dengue/diagnosis, Surveillance, biology, Mediterranean Region, Aedes albopictus, Geography, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, MESH: Yellow Fever/epidemiology, lcsh:R858-859.7, Yellow fever, Cartography, MESH: Forecasting, General Computer Science, 030231 tropical medicine, MESH: Dengue/epidemiology, Mosquito Vectors, lcsh:Computer applications to medicine. Medical informatics, World Health Organization, MESH: Mediterranean Region/epidemiology, 03 medical and health sciences, Zika, MESH: World Health Organization, Species Specificity, MESH: Geographic Mapping, Yellow Fever, medicine, MESH: Species Specificity, Animals, Humans, MESH: Humans, business.industry, Research, Public Health, Environmental and Occupational Health, 15. Life on land, medicine.disease, biology.organism_classification, General Business, Management and Accounting, Spatial model, 030104 developmental biology, Culicidae, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, business, MESH: Culicidae, Forecasting
Abstract

Background Aedes-borne diseases as dengue, zika, chikungunya and yellow fever are an emerging problem worldwide, being transmitted by Aedes aegypti and Aedes albopictus. Lack of up to date information about the distribution of Aedes species hampers surveillance and control. Global databases have been compiled but these did not capture data in the WHO Eastern Mediterranean Region (EMR), and any models built using these datasets fail to identify highly suitable areas where one or both species may occur. The first objective of this study was therefore to update the existing Ae. aegypti (Linnaeus, 1762) and Ae. albopictus (Skuse, 1895) compendia and the second objective was to generate species distribution models targeted to the EMR. A final objective was to engage the WHO points of contacts within the region to provide feedback and hence validate all model outputs. Methods The Ae. aegypti and Ae. albopictus compendia provided by Kraemer et al. (Sci Data 2:150035, 2015; Dryad Digit Repos, 2015) were used as starting points. These datasets were extended with more recent species and disease data. In the next step, these sets were filtered using the Köppen–Geiger classification and the Mahalanobis distance. The occurrence data were supplemented with pseudo-absence data as input to Random Forests. The resulting suitability and maximum risk of establishment maps were combined into hard-classified maps per country for expert validation. Results The EMR datasets consisted of 1995 presence locations for Ae. aegypti and 2868 presence locations for Ae. albopictus. The resulting suitability maps indicated that there exist areas with high suitability and/or maximum risk of establishment for these disease vectors in contrast with previous model output. Precipitation and host availability, expressed as population density and night-time lights, were the most important variables for Ae. aegypti. Host availability was the most important predictor in case of Ae. albopictus. Internal validation was assessed geographically. External validation showed high agreement between the predicted maps and the experts’ extensive knowledge of the terrain. Conclusion Maps of distribution and maximum risk of establishment were created for Ae. aegypti and Ae. albopictus for the WHO EMR. These region-specific maps highlighted data gaps and these gaps will be filled using targeted monitoring and surveillance. This will increase the awareness and preparedness of the different countries for Aedes borne diseases. Electronic supplementary material The online version of this article (10.1186/s12942-018-0125-0) contains supplementary material, which is available to authorized users.

Published
2018

18. Three-dimensional Simulation of Quantitative Ultrasound in Cancellous Bone using the Echographic Response of a Metallic Pin

Author

Yoshiki Nagatani, Salah Naili, Vu-Hieu Nguyen, Séraphin Guipieri, Guillaume Haїat, Christine Chappard, Didier Geiger, Department of Electronics [Kobe, Japan], Kobe City College of Technology [Kobe, Japan], Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire de Modélisation et Simulation Multi Echelle (MSME), Université Paris-Est Marne-la-Vallée (UPEM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Bioingénierie et Bioimagerie Ostéo-articulaires, Biomécanique et Biomatériaux Ostéo-Articulaires (B2OA (UMR_7052)), École nationale vétérinaire - Alfort (ENVA)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), This study was supported in part by KAKENHI (Grant Number 25871038 and 16K01431) from the Japan Society for the Promotion of Science (JSPS) and the PRTS program (project OsseoWave n°ANR-13-PRTS-0015-02) of French National Research Agency (ANR). This paper has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement No 682001, project ERC Consolidator Grant 2015 BoneImplant)., Haiat, Guillaume, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA), and Centre National de la Recherche Scientifique (CNRS)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Université Paris-Est Marne-la-Vallée (UPEM)

Subjects
FDTD Simulation, Materials science, Swine, FOS: Physical sciences, 3d model, Reflector (antenna), Physics - Classical Physics, Bone Nails, 01 natural sciences, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, 0302 clinical medicine, Spine surgery, Imaging, Three-Dimensional, 0103 physical sciences, medicine, Animals, Radiology, Nuclear Medicine and imaging, Femur, 010301 acoustics, Ultrasonography, Discopathy, Radiological and Ultrasound Technology, 3D Model, Soft tissue, Classical Physics (physics.class-ph), Physics - Medical Physics, [PHYS.MECA.ACOU]Physics [physics]/Mechanics [physics]/Acoustics [physics.class-ph], Vertebral body, Quantitative ultrasound, Three dimensional simulation, medicine.anatomical_structure, Metals, Models, Animal, Cancellous Bone, Medical Physics (physics.med-ph), Quantitative ultrasound (QUS), [PHYS.MECA.ACOU] Physics [physics]/Mechanics [physics]/Acoustics [physics.class-ph], Cancellous bone, Biomedical engineering
Abstract

Degenerative discopathy is a common pathology that may require spine surgery. A metallic cylindrical pin is inserted into the vertebral body to maintain soft tissues and may be used as a reflector of ultrasonic wave to estimate bone density. The first aim of this paper is to validate a three-dimensional (3-D) model to simulate the ultrasonic propagation in a trabecular bone sample in which a metallic pin has been inserted. We also aim at determining the effect of changes of bone volume fraction (BV/TV) and of positioning errors on the quantitative ultrasound (QUS) parameters in this specific configuration. The approach consists in coupling finite-difference time-domain simulation with X-ray microcomputed tomography. The correlation coefficient between experimental and simulated speed of sound (SOS)—respectively, broadband ultrasonic attenuation (BUA)—was equal to 0.90 (respectively, 0.55). The results show a significant correlation of SOS with BV/TV ( R = 0.82), while BUA values exhibit a nonlinear behavior versus BV/TV. The orientation of the pin should be controlled with an accuracy of around 1° to obtain accurate results. The results indicate that using the ultrasonic wave reflected by a pin has a potential to estimate the bone density. SOS is more reliable than BUA due to its lower sensitivity to the tilt angle.

Published
2017

19. High Rates of Neutralizing Antibodies to Toscana and Sandfly Fever Sicilian Viruses in Livestock, Kosovo

Author

Kurtesh Sherifi, Rémi N. Charrel, Kristaq Berxholi, Arber Taraku, Nazli Ayhan, Emergence des Pathologies Virales (EPV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM), University of Prishtina, Agricultural University of Tirana, This work was supported in part by the European Virus Archive Goes Global project, which has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement no. 653316, the EDENext FP7-no. 261504 European Union project and this paper is catalogued by the EDENext Steering Committee as EDENext469 (http://www.edenext.eu). The work of N.A. and R.N.C. was conducted under the frame of EurNegVec COST Action TD1303. N.A. is supported by the Fondation Mediterranee Infection., European Project: 653316,H2020,H2020-INFRAIA-2014-2015,EVAg(2015), European Project: 261504,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,EDENEXT(2011), BUISINE, Soline, European Virus Archive goes global - EVAg - - H20202015-04-01 - 2019-03-31 - 653316 - VALID, and Biology and control of vector-borne infections in Europe - EDENEXT - - EC:FP7:HEALTH2011-01-01 - 2015-06-30 - 261504 - VALID

Subjects
0301 basic medicine, Phlebovirus, Epidemiology, Kosovo, vector-borne infections, lcsh:Medicine, Mediterranean, Antibodies, Viral, 0302 clinical medicine, Phlebotomus Fever, Sandfly Fever Sicilian Virus, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Toscana virus, biology, Incidence, Dispatch, 3. Good health, Infectious Diseases, Epidemiological Monitoring, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Bunyaviridae, Microbiology (medical), Livestock, 030231 tropical medicine, Arbovirus, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, Balkan, medicine, Animals, Humans, lcsh:RC109-216, viruses, sandfly fever Sicilian virus, Sheep, lcsh:R, Sandfly fever Naples virus, biology.organism_classification, medicine.disease, Antibodies, Neutralizing, Virology, Insect Vectors, Sandfly, 030104 developmental biology, arbovirus, High Rates of Neutralizing Antibodies to Toscana and Sandfly Fever Sicilian Viruses in Livestock, Kosovo, Cattle, Psychodidae, sand flies
Abstract

Kurtesh Sherifi and Rémi N. Charrel contributed equally to this article; International audience; Toscana and sandfly fever Sicilian viruses (TOSV and SFSV, respectively), both transmitted by sand flies, are prominent human pathogens in the Old World. Of 1,086 serum samples collected from cattle and sheep during 2013 in various regions of Kosovo (Balkan Peninsula), 4.7% and 53.4% had neutralizing antibodies against TOSV and SFSV, respectively.

Published
2017

20. Larval nutritional stress affects vector life history traits and human malaria transmission

Author

Thierry Lefèvre, Amélie Vantaux, Anna Cohuet, Olivier Roux, Benjamin Roche, Kounbobr Roch Dabiré, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Institut de Recherche en Sciences de la Santé (IRSS), CNRST, Transmission-Interactions-Adaptations hôtes/vecteurs/pathogènes (MIVEGEC-TRIAD), Evolution des Systèmes Vectoriels (ESV), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud]), Institut de Recherche en Sciences de la Santé (IRSS) / Centre Muraz, Unité de modélisation mathématique et informatique des systèmes complexes [Bondy] (UMMISCO), Université Cadi Ayyad [Marrakech] (UCA)-Université de Yaoundé I-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Institut de la francophonie pour l'informatique-Université Pierre et Marie Curie - Paris 6 (UPMC), Diversity, ecology, evolution & Adaptation of arthropod vectors (MIVEGEC-DEEVA), This study was funded by the ANR grant 11-PDOC-006-01 to TL., We would like to thank all of the children and their parents who participated in this study, as well as the local authorities for their support, and Andrea Yockey-Dejean for proofreading the paper. We are very grateful to the IRSS staff in Burkina Faso for technical assistance., and Institut de Recherche pour le Développement (IRD)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université de Yaoundé I-Institut de la francophonie pour l'informatique-Université Cheikh Anta Diop [Dakar, Sénégal] (UCAD)-Université Gaston Bergé (Saint-Louis, Sénégal)-Université Cadi Ayyad [Marrakech] (UCA)

Subjects
0301 basic medicine, media_common.quotation_subject, [SDV]Life Sciences [q-bio], Plasmodium falciparum, Zoology, Insect, MESH: Insect Vectors, Biology, Article, law.invention, Life history theory, 03 medical and health sciences, MESH: Plasmodium falciparum/growth & development, law, Stress, Physiological, Anopheles, parasitic diseases, medicine, Gametocyte, Animals, Humans, MESH: Animals, MESH: Stress, Physiological, Life History Traits, media_common, Larva, Multidisciplinary, MESH: Humans, MESH: Life History Traits, MESH: Anopheles/parasitology, Ecology, fungi, MESH: Anopheles/growth & development, medicine.disease, Fecundity, 3. Good health, Insect Vectors, Malaria, MESH: Larva/parasitology, MESH: Malaria/transmission, 030104 developmental biology, Transmission (mechanics), MESH: Larva/growth & development, Vector (epidemiology), Female, MESH: Female
Abstract

Exposure to stress during an insect’s larval development can have carry-over effects on adult life history traits and susceptibility to pathogens. We investigated the effects of larval nutritional stress for the first time using field mosquito vectors and malaria parasites. In contrast to previous studies, we show that larval nutritional stress may affect human to mosquito transmission antagonistically: nutritionally deprived larvae showed lower parasite prevalence for only one gametocyte carrier; they also had lower fecundity. However, they had greater survival rates that were even higher when infected. When combining these opposing effects into epidemiological models, we show that larval nutritional stress induced a decrease in malaria transmission at low mosquito densities and an increase in transmission at high mosquito densities, whereas transmission by mosquitoes from well-fed larvae was stable. Our work underscores the importance of including environmental stressors towards understanding host–parasite dynamics to improve disease transmission models and control.

Published
2016

21. Integrated Analysis of Environment, Cattle and Human Serological Data: Risks and Mechanisms of Transmission of Rift Valley Fever in Madagascar

Author

Annelise Tran, Vladimir Grosbois, Jean-Pierre Ravalohery, Fanjasoa Rakotomanana, Jean-Michel Heraud, Soa Fy Andriamandimby, Christophe Rogier, Seta Andriamamonjy, Véronique Chevalier, Benoit Durand, Marie-Marie Olive, Animal et gestion intégrée des risques (UPR AGIRs), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Unité de Virologie [Antananarivo, Madagascar] (IPM), Institut Pasteur de Madagascar, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Laboratoire de santé animale, sites de Maisons-Alfort et de Dozulé, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Réseau International des Instituts Pasteur (RIIP), This study was supported in part by funds raised by (i) CIRAD (ii) the Centre National d'Etudes Spatiales (CNES, grant # 131163/00) (iii) the Institut Pasteur de Madagascar. Human field work was funded by the Institut Pasteur of Madagascar (Internal Project through the ZORA (ZOonoses, Rodent and Arboviruses) project and the Centers for Disease Control and Prevention (CDC, and Cooperative Agreement #U51/IP000327). Moreover, this material is based upon work supported by the U. S. Department of Homeland Security under the Center of Excellence of Emerging and Zoonotic Animal Diseases Grant Award Number 2010-ST061-AG0001. Cattle study was supported in part by funds raised by World Health Organization (WHO) and the Food and Agriculture Organization of the United Nations (FAO) through the Central Emergency Response Fund of the United Nations. The views and conclusions contained in this paper are those of the authors and should not be interpreted as necessarily representing the official policies, either explicit or implicit, of the U. S. Department of Homeland Security. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Subjects
Veterinary medicine, Epidemiology, Pathology and Laboratory Medicine, law.invention, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Analyse du risque, MESH: Cattle Diseases, MESH: Animals, Neglected tropical diseases, Mammals, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, MESH: Middle Aged, 000 - Autres thèmes, Fièvre de la Vallée du Rift, Anopheles, Ruminants, 3. Good health, Transmission (mechanics), MESH: Young Adult, Densité de population, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Enzootic, Infectious diseases, L72 - Organismes nuisibles des animaux, Genre humain, Bétail, Livestock, lcsh:RC955-962, MESH: Culex, Microbiology, MESH: Anopheles, 03 medical and health sciences, MESH: Cross-Sectional Studies, Madagascar, MESH: Humans, MESH: Seroepidemiologic Studies, Tropical diseases, Public Health, Environmental and Occupational Health, Organisms, lcsh:RA1-1270, MESH: Adult, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, 15. Life on land, medicine.disease, Invertebrates, Insect Vectors, 030104 developmental biology, Africa, Cattle, MESH: Female, MESH: Antibodies, Viral, 0301 basic medicine, RNA viruses, Cattle Diseases, Disease Vectors, L73 - Maladies des animaux, Mosquitoes, Serology, Geographical Locations, MESH: Madagascar, law, Zoonoses, Facteur de risque, Bunyaviruses, Medicine and Health Sciences, MESH: Rift Valley Fever, Comportement humain, Rift Valley fever, 2. Zero hunger, biology, lcsh:Public aspects of medicine, Agriculture, Facteur du milieu, Medical microbiology, Insects, MESH: Cattle, Vecteur de maladie, Vertebrates, Viruses, MESH: Rift Valley fever virus, Seasons, Pathogens, Research Article, lcsh:Arctic medicine. Tropical medicine, Zone humide, Arthropoda, Distribution géographique, Culex, 030231 tropical medicine, Viral diseases, MESH: Insect Vectors, Virus de la fièvre de la vallée du Rift, Sérologie, Bovines, medicine, Seroprevalence, Animals, MESH: Environment, Transmission des maladies, Biology and life sciences, Viral pathogens, Morbidité, biology.organism_classification, Rift Valley fever virus, MESH: Male, Microbial pathogens, Amniotes, People and Places, Earth Sciences, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract

Background Rift Valley fever (RVF) is a vector-borne disease affecting ruminants and humans. Madagascar was heavily affected by RVF in 2008–2009, with evidence of a large and heterogeneous spread of the disease. The identification of at-risk environments is essential to optimize the available resources by targeting RVF surveillance in Madagascar. Herein, the objectives of our study were: (i) to identify the environmental factors and areas favorable to RVF transmission to both cattle and human and (ii) to identify human behaviors favoring human infections in Malagasy contexts. Methodology/Principal Findings First, we characterized the environments of Malagasy communes using a Multiple Factor Analysis (MFA). Then, we analyzed cattle and human serological data collected at national level using Generalized Linear Mixed Models, with the individual serological status (cattle or human) as the response, and MFA factors, as well as other potential risk factors (cattle density, human behavior) as explanatory variables. Cattle and human seroprevalence rates were positively associated to humid environments (p, Author Summary Rift Valley fever virus (RVFV) is a pathogen that causes a vector-borne tropical disease. The disease affects ruminants and humans and severely impacts the health and economy of affected countries. Madagascar was heavily affected by Rift Valley fever (RVF) in 2008–2009, with evidence of a large and heterogeneous spread of the disease. Our study aims at identifying environmental and human-related risk factors for RVFV transmission. First, we characterized Malagasy environments according to their putative influence on RVFV mosquito density and population dynamics. Then we statistically analyzed cattle and human serological data collected at a national level with the individual serological status as response, and Malagasy environments previously characterized by climatic and landscape variables as well as other potential risk factors as explanatory variables. Our results identified humid environments of the western, north-western and eastern parts of the island as risky areas. The identification of at-risk environments is essential to focus veterinary surveillance and control of RVFV.

Published
2016

22. Neutrophil Extracellular Traps are Involved in the Innate Immune Response to Infection with Leptospira

Author

Emilia Scharrig, María Florencia Ferrer, Agostina Carestia, Mathieu Picardeau, Maia Cédola, Ricardo Martín Gómez, Mirta Schattner, Gabriela Pretre, Ricardo Drut, CCT La Plata-CONICET-Facultad de Ciencias Veterinarias [La Plata, PBA, Argentine], Universidad Nacional de la Plata [Argentine] (UNLP), Consejo Nacional de Investigaciones Científicas y Técnicas [Buenos Aires] (CONICET), Children Hospital 'Superiora Sor María Ludovica' LA PLATA, Biologie des Spirochètes / Biology of Spirochetes, Institut Pasteur [Paris], This work was supported by PICTs grant 12-0434 (RMG) and 11-733 (MS) from ANPCyT. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript., Conceived and designed the experiments: MP MS RMG. Performed the experiments: ES AC MFF GP. Analyzed the data: MC RD. Contributed reagents/materials/analysis tools: MP. Wrote the paper: MS RMG., and Institut Pasteur [Paris] (IP)

Subjects
Male, lcsh:Arctic medicine. Tropical medicine, Neutrophils, lcsh:RC955-962, [SDV]Life Sciences [q-bio], Inflammation, Extracellular Traps, Microbiology, purl.org/becyt/ford/1 [https], Ciencias Biológicas, Mice, 03 medical and health sciences, neutrophils, Immunity, In vivo, Leptospira, medicine, Animals, Humans, leptospirosis, Leptospirosis, purl.org/becyt/ford/1.6 [https], Ciencias Exactas, 030304 developmental biology, 0303 health sciences, Innate immune system, biology, 030306 microbiology, lcsh:Public aspects of medicine, Public Health, Environmental and Occupational Health, lcsh:RA1-1270, Nets, Neutrophil extracellular traps, biology.organism_classification, Immunity, Innate, 3. Good health, Mice, Inbred C57BL, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, medicine.symptom, Leptospira interrogans, Virología, Ex vivo, CIENCIAS NATURALES Y EXACTAS, Research Article
Abstract

NETosis is a process by which neutrophils extrude their DNA together with bactericidal proteins that trap and/or kill pathogens. In the present study, we evaluated the ability of Leptospira spp. to induce NETosis using human ex vivo and murine in vivo models. Microscopy and fluorometric studies showed that incubation of human neutrophils with Leptospira interrogans serovar Copenhageni strain Fiocruz L1-130 (LIC) resulted in the release of DNA extracellular traps (NETs). The bacteria number, pathogenicity and viability were relevant factors for induction of NETs, but bacteria motility was not. Entrapment of LIC in the NETs resulted in LIC death; however, pathogenic but not saprophytic Leptospira sp. exerted nuclease activity and degraded DNA. Mice infected with LIC showed circulating NETs after 2 days post-infection (dpi). Depletion of neutrophils with mAb1A8 significantly reduced the amount of intravascular NETs in LIC-infected mice, increasing bacteremia at 3 dpi. Although there was a low bacterial burden, scarce neutrophils and an absence of inflammation in the early stages of infection in the kidney and liver, at the beginning of the leptospiruric phase, the bacterial burden was significantly higher in kidneys of neutrophil-depleted-mice compared to non-depleted and infected mice. Surprisingly, interstitial nephritis was of similar intensity in both groups of infected mice. Taken together, these data suggest that LIC triggers NETs, and that the intravascular formation of these DNA traps appears to be critical not only to prevent early leptospiral dissemination but also to preclude further bacterial burden., Instituto de Biotecnologia y Biologia Molecular, Facultad de Ciencias Exactas, Facultad de Ciencias Médicas

Published
2015

23. Concerns about the widespread use of rodent models for human risk assessments of endocrine disruptors

Author

Gabriel Livera, René Frydman, Delphine Moison, Vincent Muczynski, Alexandra Benachi, René Habert, R. Lambrot, Abdelali Lehraiki, Virginie Rouiller-Fabre, Geraldine Delbes, Tiphany Grisin, Christine Levacher, Marie-Justine Guerquin, Sébastien Messiaen, Thierry N’Tumba-Byn, Stabilité génétique, Cellules Souches et Radiations (SCSR (U_967)), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Service de gynécologie-obstétrique, médecine de la reproduction [Béclère], Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Armand Frappier (INRS-IAF), Institut National de la Recherche Scientifique [Québec] (INRS)-Réseau International des Instituts Pasteur (RIIP), The work of our group presented in this paper was supported byUniversité Paris Diderot-Paris 7, CEA, INSERM, the FrenchAgence pour la Santé et la Sécurité dans l’Environnement et le Travail (AFSSET), the French Agence Nationale de SécuritéSanitaire de l’Alimentation, de l’Environnement et du Travail(ANSES Contrat EST62010/2/046), the Agence Nationale de laRecherche (ANR, contrat Phtalatestis and contrat MECABPA)and the Ministère de l’Ecologie, du Développement Durable,des Transports et du Logement (Programme ANTIOPES –Storm). None of the authors received any personal financialremuneration or funding for research studies from anychemical industrial company., ANR-07-SEST-0019,PHTALATESTIS,Effets et mécanismes d'action des phtalates sur le développement et les fonctions du testicule chez la souris et l'homme(2007), ANR-11-CESA-0001,MECABPA,Effets et mécanismes d'action du bisphénol A (BPA) sur le développement et les fonctions des gonades foetales chez la souris, la brebis et l'homme(2011), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), AP-HP - Hôpital Antoine Béclère [Clamart], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11), Courcelles, Michel, Santé-environnement et Santé-travail - Effets et mécanismes d'action des phtalates sur le développement et les fonctions du testicule chez la souris et l'homme - - PHTALATESTIS2007 - ANR-07-SEST-0019 - SEST - VALID, Contaminants et Environnements : Métrologie, santé, Adaptabilité, Comportements et Usages - Effets et mécanismes d'action du bisphénol A (BPA) sur le développement et les fonctions des gonades foetales chez la souris, la brebis et l'homme - - MECABPA2011 - ANR-11-CESA-0001 - CESA - VALID, Cellules Souches et Radiations (SCSR - U 967), Université Paris-Sud - Paris 11 (UP11) - Commissariat à l'énergie atomique et aux énergies alternatives (CEA) - Université Paris Diderot - Paris 7 (UPD7) - Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris-Sud - Paris 11 (UP11) - Assistance publique - Hôpitaux de Paris (AP-HP) - Hôpital Antoine Béclère, and Institut National de la Recherche Scientifique [Québec] (INRS) - Réseau International des Instituts Pasteur (RIIP) - Institut Armand Frappier

Subjects
Animal Experimentation, Male, Embryology, medicine.medical_specialty, Cell type, Rodent, [SDV]Life Sciences [q-bio], Retinoic acid, Rodentia, Review, Endocrine Disruptors, Risk Assessment, Mice, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Endocrinology, Internal medicine, biology.animal, Testis, Toxicity Tests, medicine, Animals, Humans, Endocrine system, Animal testing, [SDV.BDLR] Life Sciences [q-bio]/Reproductive Biology, Gametogenesis, 030304 developmental biology, 0303 health sciences, Fetus, 030219 obstetrics & reproductive medicine, biology, Phthalate, Obstetrics and Gynecology, Cell Biology, Rats, 3. Good health, [SDV.TOX] Life Sciences [q-bio]/Toxicology, [SDV] Life Sciences [q-bio], Reproductive Medicine, chemistry, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Models, Animal, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract

International audience; Fetal testis is a major target of endocrine disruptors (EDs). During the last 20 years, we have developed an organotypic culture system that maintains the function of the different fetal testis cell types and have used this approach as a toxicological test to evaluate the effects of various compounds on gametogenesis and steroidogenesis in rat, mouse and human testes. We named this test rat, mouse and human fetal testis assay. With this approach, we compared the effects of six potential EDs ((mono-(2-ethylhexyl) phthalate (MEHP), cadmium, depleted uranium, diethylstilboestrol (DES), bisphenol A (BPA) and metformin) and one signalling molecule (retinoic acid (RA)) on the function of rat, mouse and human fetal testis at a comparable developmental stage. We found that the response is similar in humans and rodents for only one third of our analyses. For instance, RA and MEHP have similar negative effects on gametogenesis in the three species. For another third of our analyses, the threshold efficient concentrations that disturb gametogenesis and/or steroidogenesis differ as a function of the species. For instance, BPA and metformin have similar negative effects on steroidogenesis in human and rodents, but at different threshold doses. For the last third of our analyses, the qualitative response is species specific. For instance, MEHP and DES affect steroidogenesis in rodents, but not in human fetal testis. These species differences raise concerns about the extrapolation of data obtained in rodents to human health risk assessment and highlight the need of rigorous comparisons of the effects in human and rodent models, when assessing ED risk.

Published
2014

24. ICAM-2 regulates vascular permeability and N-cadherin localization through ezrin-radixin-moesin (ERM) proteins and Rac-1 signalling

Author

Nicola H. Dryden, Anna M. Randi, Valérie Amsellem, Roberta Martinelli, Justin C. Mason, Felicity N. E. Gavins, Graeme M. Birdsey, Patric Turowski, Dorian O. Haskard, Lourdes Osuna Almagro, BMC, Ed., Imperial College for Translational and Experimental Medicine, Imperial College London, Cell Biology, UCL Institute of Ophthalmology, Division of Brain Sciences, Imperial College London-Hammersmith Hospital, This paper was supported by grants from the British Heart Foundation and the European Community (NoE MAIN 502935), and British Heart Foundation

Subjects
rac1 GTP-Binding Protein, Angiogenesis, Vascular permeability, Biochemistry, Mice, CYTOPLASMIC DOMAIN, [SDV.BBM.BC] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Cell adhesion molecule, Microfilament Proteins, Ce ll adhesion, Gap Junctions, Intercellular adhesion molecule, Cadherins, Cell-cell junctions, Cell biology, Rac-1, Protein Transport, ERM, Life Sciences & Biomedicine, Protein Binding, Signal Transduction, Biochemistry & Molecular Biology, ICAM-2, VE-CADHERIN, Biology, Permeability, ADHESION MOLECULES, TUMOR ANGIOGENESIS, Cell-cell junction, Endothelial, Adherens junction, HUMAN ENDOTHELIAL-CELLS, Capillary Permeability, RHO, Antigens, CD, Cell Line, Tumor, Human Umbilical Vein Endothelial Cells, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biochemistry [q-bio.BM], Cell adhesion, Molecular Biology, ADHERENS JUNCTION, N-Cadherin, 0604 Genetics, Science & Technology, Binding Sites, Cadherin, Research, Contact inhibition, 0601 Biochemistry And Cell Biology, Membrane Proteins, IN-VITRO, Cell Biology, Cytoskeletal Proteins, GTPASES, Cell Adhesion Molecules
Abstract

Background Endothelial junctions control functions such as permeability, angiogenesis and contact inhibition. VE-Cadherin (VECad) is essential for the maintenance of intercellular contacts. In confluent endothelial monolayers, N-Cadherin (NCad) is mostly expressed on the apical and basal membrane, but in the absence of VECad it localizes at junctions. Both cadherins are required for vascular development. The intercellular adhesion molecule (ICAM)-2, also localized at endothelial junctions, is involved in leukocyte recruitment and angiogenesis. Results In human umbilical vein endothelial cells (HUVEC), both VECad and NCad were found at nascent cell contacts of sub-confluent monolayers, but only VECad localized at the mature junctions of confluent monolayers. Inhibition of ICAM-2 expression by siRNA caused the appearance of small gaps at the junctions and a decrease in NCad junctional staining in sub-confluent monolayers. Endothelioma lines derived from WT or ICAM-2-deficient mice (IC2neg) lacked VECad and failed to form junctions, with loss of contact inhibition. Re-expression of full-length ICAM-2 (IC2 FL) in IC2neg cells restored contact inhibition through recruitment of NCad at the junctions. Mutant ICAM-2 lacking the binding site for ERM proteins (IC2 ΔERM) or the cytoplasmic tail (IC2 ΔTAIL) failed to restore junctions. ICAM-2-dependent Rac-1 activation was also decreased in these mutant cell lines. Barrier function, measured in vitro via transendothelial electrical resistance, was decreased in IC2neg cells, both in resting conditions and after thrombin stimulation. This was dependent on ICAM-2 signalling to the small GTPase Rac-1, since transendothelial electrical resistance of IC2neg cells was restored by constitutively active Rac-1. In vivo, thrombin-induced extravasation of FITC-labeled albumin measured by intravital fluorescence microscopy in the mouse cremaster muscle showed that permeability was increased in ICAM-2-deficient mice compared to controls. Conclusions These results indicate that ICAM-2 regulates endothelial barrier function and permeability through a pathway involving N-Cadherin, ERMs and Rac-1.

Published
2014

25. Genetically engineered T cells bearing chimeric nanoconstructed receptors harboring TAG-72-specific camelid single domain antibodies as targeting agents

Author

Zahra Sharifzadeh, S. Moein Moghimi, Fatemeh Rahbarizadeh, Davoud Ahmadvand, Mohammad Ali Shokrgozar, Fereidoun Mahboudi, Fatemeh Rahimi Jamnani, Institut Pasteur d'Iran, Réseau International des Instituts Pasteur (RIIP), Department of Medical Biotechnology, Tarbiat Modares University [Tehran]-Faculty of Medical Sciences, School of Allied Medical Sciences, Tehran University of Medical Sciences, Biotechnology Research Center, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Nano-Science Center [Copenhagen], Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU)-Faculty of Science [Copenhagen], University of Copenhagen = Københavns Universitet (KU), Nanomedicine Laboratory, Centre of Pharmaceutical Nanotechnology and Nanotoxicology-University of Copenhagen = Københavns Universitet (KU), and This paper was supported by Pasteur Institute of Iran, Tehran, Iran, the Biotechnology Committee of Tarbiat Modares University (TMU-88-8-67), Tehran, Iran and from the Danish Agency for Science, Technology and Innovative (det Strategiske Forskningsråd) reference 09-065746/DSF to SMM.

Subjects
Cancer Research, Leukemia, T-Cell, medicine.medical_treatment, T cell, Recombinant Fusion Proteins, T-Lymphocytes, Biology, Lymphocyte Activation, Transfection, Immunotherapy, Adoptive, 03 medical and health sciences, 0302 clinical medicine, Immune system, Antigen, Antibody Specificity, Antigens, Neoplasm, Peptide Library, medicine, Animals, Humans, Chimeric antigen receptor, 030304 developmental biology, Glycoproteins, 0303 health sciences, Immunogenicity, CD28, Immunotherapy, Single-Domain Antibodies, Molecular biology, 3. Good health, Cell biology, Oligoclonal single domain antibodies, Receptors, Antigen, medicine.anatomical_structure, Oncology, TAG-72, 030220 oncology & carcinogenesis, Immunoglobulin G, Colonic Neoplasms, biology.protein, Carcinoma, Squamous Cell, [SDV.IMM]Life Sciences [q-bio]/Immunology, Antibody, Genetic Engineering, Camelids, New World, HT29 Cells, Signal Transduction
Abstract

International audience; Despite the preclinical success of adoptive therapy with T cells bearing chimeric nanoconstructed antigen receptors (CARs), certain limitations of this therapeutic approach such as the immunogenicity of the antigen binding domain, the emergence of tumor cell escape variants and the blocking capacity of soluble antigen still remain. Here, we address these issues using a novel CAR binding moiety based on the oligoclonal camelid single domain antibodies. A unique set of 13 single domain antibodies were selected from an immunized camel phage library based on their target specificity and binding affinity. A combination of these single domain antibodies was used to generate four tumor associated glycoprotein (TAG-72)-specific CARs harboring an identical antigen binding site, but with different signaling and spacer domains. Although all four CARs were functionally active against the TAG-72 expressing tumor cells, the combination of CD3ζ, OX40, CD28 as well as the CH3-CH2-hinge-hinge domains most efficiently triggered T cell activation. Importantly, CAR mediated functions were not blocked by the soluble TAG-72 antigen at a supraphysiological concentration. Our approach may have the potential to reverse multiple tumor immune evasion mechanisms, avoid CAR immunogenicity, and overcome problems in cancer gene therapy with engineered nanoconstructs.

Published
2012

26. High-pressure intrapleural chemotherapy: feasibility in the pig model

Author

Bernard Royer, Alain Bernard, Bruno Chauffert, Pablo Ortega-Deballon, Olivier Facy, Guy Magnin, Pierre-Benoit Pagès, Sylvain Ladoire, Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Service de Chirurgie Digestive, Cancérologique, Générale, Endocrinienne et Urgences (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Service de chirurgie cardio-vasculaire, Service d'anesthésie réanimation, Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Laboratoire de Pharmacologie Clinique et Toxicologie [Besancon], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz-Université de Franche-Comté ( UFC ), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC ( HOTE GREFFON ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Etablissement français du sang [Bourgogne-France-Comté] ( EFS [Bourgogne-France-Comté] ) -Université de Franche-Comté ( UFC ), This paper was supported by research grants from the French National League against Cancer, from the Regional Council of Burgundy and from the University Hospital of Dijon (France)., Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Laboratoire de Pharmacologie Clinique et Toxicologie [CHRU Besancon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Interactions hôte-greffon-tumeur, ingénierie cellulaire et génique - UFC (UMR INSERM 1098) (RIGHT), Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Université de Franche-Comté (UFC), BMC, Ed., Service de chirurgie cardio-vasculaire et thoracique (CHU Dijon), and Service d'anesthésie - réanimation chirurgicale [CHU de Dijon]

Subjects
medicine.medical_specialty, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, Swine, Pleural Neoplasms, lcsh:Surgery, Intra arterial chemotherapy, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, lcsh:RC254-282, Deoxycytidine, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, 03 medical and health sciences, chemistry.chemical_compound, pressure, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Surgical oncology, Neoplasms, Antineoplastic Combined Chemotherapy Protocols, medicine, Tumor Cells, Cultured, Animals, Humans, Intrapleural chemotherapy, Pleural Neoplasm, [ SDV.MHEP.CHI ] Life Sciences [q-bio]/Human health and pathology/Surgery, pig model, Cisplatin, business.industry, Research, Pig model, lcsh:RD1-811, intrapleural intracavitary chemotherapy, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Gemcitabine, 3. Good health, Surgery, 030228 respiratory system, chemistry, Oncology, 030220 oncology & carcinogenesis, High pressure, Feasibility Studies, Female, business, medicine.drug
Abstract

Background The usual treatments for pleural malignancies are mostly palliative. In contrast, peritoneal malignancies are often treated with a curative intent by cytoreductive surgery and intraperitoneal chemotherapy. As pressure has been shown to increase antitumor efficacy, we applied the concept of high-pressure intracavitary chemotherapy to the pleural space in a swine model. Methods Cisplatin and gemcitabine were selected because of their antineoplasic efficacy in vitro in a wide spectrum of cancer cell lines. The pleural cavity of 21 pigs was filled with saline solution; haemodynamic and respiratory parameters were monitored. The pressure was increased to 15-25 cm H2O. This treatment was associated with pneumonectomy in 6 pigs. Five pigs were treated with chemotherapy under pressure. Results The combination of gemcitabine (100 mg/l) and cisplatin (30 mg/l) was highly cytotoxic in vitro. The maximum tolerated pressure was 20 cm H20, due to haemodynamic failure. Pneumonectomy was not tolerated, either before or after pleural infusion. Five pigs survived intrapleural chemotherapy associating gemcitabine and cisplatin with 20 cm H2O pressure for 60 min. Conclusions High-pressure intrapleural chemotherapy is feasible in pigs. Further experiments will establish the pharmacokinetics and determine whether the benefit already shown in the peritoneum is also obtained in the pleura.

Published
2012

27. An integrated encyclopedia of DNA elements in the human genome

Author

Robert Altshuler, Laura Elnitski, Michael Anaya, Alec Victorsen, Deborah Winter, Javier Herrero, Katherine Varley, Andrea Sboner, Oscar Junhong Luo, Marco Mariotti, Cristina Sisu, Mike Kay, Timothy Dreszer, Jane Loveland, Alexandra Bignell, Ewan Birney, Tim @timjph Hubbard, Kuljeet Sandhu, Eric Haugen, Chris Gunter, Alexej Abyzov, Lucas Ward, Georgi Marinov, Michael Pazin, Thomas Gingeras, Alexander Dobin, Kimberly Foss, Xianjun Dong, Benoit Miotto, Piotr Mieczkowski, Cedric Notredame, Andrew Berry, Shawn Gillespie, Axel Visel, Shawn Levy, Richard Sandstrom, Jose M Gonzalez, Melissa Fullwood, Timo Lassmann, Michael Tress, Julien Lagarde, Kevin Yip, Leslie Adams, Sylvain Foissac, Bronwen Aken, Piero Carninci, Suganthi Balasubramanian, Andrea Tanzer, Sarah Djebali, Michael Hoffman, Gloria Despacio-Reyes, Peter Park, Felix Kokocinski, Katherine Fisher-Aylor, Juan M Vaquerizas, Peggy Farnham, Patrick Collins, Amonida Zadissa, Pedro Ferreira, Philippe Batut, Michael Snyder, Electra Tapanari, Adam Frankish, Paul Flicek, AMARTYA SANYAL, Tyler Alioto, Giovanni Bussotti, Laurence Meyer, Jingyi Jessica Li, Matthew Blow, Tristan FRUM, Roger Alexander, Rory Johnson, Charles Steward, Meizhen Zheng, Margus Lukk, Ross Hardison, Claire Davidson, Gary Saunders, Alan Boyle, Luiz Penalva, Rajinder Kaul, Lazaro Centanin, Florencia Pauli Behn, Thomas Derrien, Nathan Sheffield, Toby Hunt, Eric Nguyen, Jeff Vierstra, Konrad Karczewski, Kimberly Bell, Yanbao Yu, Hagen U Tilgner, James Taylor, Balázs Bánfai, Catherine Snow, Benjamin Vernot, Stephan Kirchmaier, Michael Sammeth, Steven Wilder, Angelika Merkel, Joanna Mieczkowska, Guoliang Li, Wei Lin, Jennifer Harrow, Thomas Oliver Auer, Daniel Barrell, Eddie Park, Alvis Brazma, Hazuki Takahashi, Nathan Johnson, Daniel Sobral, Terry Furey, Alexandre Reymond, Jonathan Mudge, Anshul Kundaje, Jose Rodriguez, Akshay Bhinge, James Gilbert, Jakub Karczewski, Venkat Malladi, Troy Whitfield, Orion Buske, Ian Dunham, Jennifer Moran, Joachim Wittbrodt, Charles B. Epstein, Laurens Wilming, Jason Gertz, Joshua Akey, Joel Rozowsky, Laboratoire de Génétique Cellulaire (LGC), 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-Institut National de la Recherche Agronomique (INRA), National Human Genome Research Institute (NHGRI), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Antonarakis, Stylianos, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Altshuler, Robert Charles, Ernst, Jason, Kellis, Manolis, Kheradpour, Pouya, Ward, Lucas D., Eaton, Matthew Lucas, Hendrix, David A., Jungreis, Irwin, Lin, Michael F., Washietl, Stefan, Lists of participants and their affiliations appear at the end of the paper and in the 'Collaboration/Projet' field., The Consortium is funded by grants from the NHGRI as follows: production grants: U54HG004570 (B. E. Bernstein), U01HG004695 (E. Birney), U54HG004563 (G. E. Crawford), U54HG004557 (T. R. Gingeras), U54HG004555 (T. J. Hubbard), U41HG004568 (W. J. Kent), U54HG004576 (R. M. Myers), U54HG004558 (M. Snyder), U54HG004592 (J. A. Stamatoyannopoulos). Pilot grants: R01HG003143 (J. Dekker), RC2HG005591 and R01HG003700 (M. C. Giddings), R01HG004456-03 (Y. Ruan), U01HG004571 (S. A. Tenenbaum), U01HG004561 (Z. Weng), RC2HG005679 (K. P. White). This project was supported in part by American Recovery and Reinvestment Act (ARRA) funds from the NHGRI through grants U54HG004570, U54HG004563, U41HG004568, U54HG004592, R01HG003143, RC2HG005591, R01HG003541,U01HG004561,RC2HG005679andR01HG003988(L. Pennacchio). In addition, work from NHGRI Groups was supported by the Intramural Research Program of the NHGRI (L. Elnitski, ZIAHG200323, E. H. Margulies, ZIAHG200341). Research in the Pennachio laboratory was performed at Lawrence Berkeley National Laboratory and at the United States Department of Energy Joint Genome Institute, Department of Energy Contract DE-AC02-05CH11231, University of California., Dunham I, Kundaje A, Aldred SF, Collins PJ, Davis CA, Doyle F, Epstein CB, Frietze S, Harrow J, Kaul R, Khatun J, Lajoie BR, Landt SG, Lee BK, Pauli F, Rosenbloom KR, Sabo P, Safi A, Sanyal A, Shoresh N, Simon JM, Song L, Trinklein ND, Altshuler RC, Birney E, Brown JB, Cheng C, Djebali S, Dong X, Dunham I, Ernst J, Furey TS, Gerstein M, Giardine B, Greven M, Hardison RC, Harris RS, Herrero J, Hoffman MM, Iyer S, Kellis M, Khatun J, Kheradpour P, Kundaje A, Lassmann T, Li Q, Lin X, Marinov GK, Merkel A, Mortazavi A, Parker SC, Reddy TE, Rozowsky J, Schlesinger F, Thurman RE, Wang J, Ward LD, Whitfield TW, Wilder SP, Wu W, Xi HS, Yip KY, Zhuang J, Pazin MJ, Lowdon RF, Dillon LA, Adams LB, Kelly CJ, Zhang J, Wexler JR, Green ED, Good PJ, Feingold EA, Bernstein BE, Birney E, Crawford GE, Dekker J, Elnitski L, Farnham PJ, Gerstein M, Giddings MC, Gingeras TR, Green ED, Guigó R, Hardison RC, Hubbard TJ, Kellis M, Kent W, Lieb JD, Margulies EH, Myers RM, Snyder M, Stamatoyannopoulos JA, Tenenbaum SA, Weng Z, White KP, Wold B, Khatun J, Yu Y, Wrobel J, Risk BA, Gunawardena HP, Kuiper HC, Maier CW, Xie L, Chen X, Giddings MC, Bernstein BE, Epstein CB, Shoresh N, Ernst J, Kheradpour P, Mikkelsen TS, Gillespie S, Goren A, Ram O, Zhang X, Wang L, Issner R, Coyne MJ, Durham T, Ku M, Truong T, Ward LD, Altshuler RC, Eaton ML, Kellis M, Djebali S, Davis CA, Merkel A, Dobin A, Lassmann T, Mortazavi A, Tanzer A, Lagarde J, Lin W, Schlesinger F, Xue C, Marinov GK, Khatun J, Williams BA, Zaleski C, Rozowsky J, Röder M, Kokocinski F, Abdelhamid RF, Alioto T, Antoshechkin I, Baer MT, Batut P, Bell I, Bell K, Chakrabortty S, Chen X, Chrast J, Curado J, Derrien T, Drenkow J, Dumais E, Dumais J, Duttagupta R, Fastuca M, Fejes-Toth K, Ferreira P, Foissac S, Fullwood MJ, Gao H, Gonzalez D, Gordon A, Gunawardena HP, Howald C, Jha S, Johnson R, Kapranov P, King B, Kingswood C, Li G, Luo OJ, Park E, Preall JB, Presaud K, Ribeca P, Risk BA, Robyr D, Ruan X, Sammeth M, Sandhu KS, Schaeffer L, See LH, Shahab A, Skancke J, Suzuki AM, Takahashi H, Tilgner H, Trout D, Walters N, Wang H, Wrobel J, Yu Y, Hayashizaki Y, Harrow J, Gerstein M, Hubbard TJ, Reymond A, Antonarakis SE, Hannon GJ, Giddings MC, Ruan Y, Wold B, Carninci P, Guigó R, Gingeras TR, Rosenbloom KR, Sloan CA, Learned K, Malladi VS, Wong MC, Barber GP, Cline MS, Dreszer TR, Heitner SG, Karolchik D, Kent W, Kirkup VM, Meyer LR, Long JC, Maddren M, Raney BJ, Furey TS, Song L, Grasfeder LL, Giresi PG, Lee BK, Battenhouse A, Sheffield NC, Simon JM, Showers KA, Safi A, London D, Bhinge AA, Shestak C, Schaner MR, Kim SK, Zhang ZZ, Mieczkowski PA, Mieczkowska JO, Liu Z, McDaniell RM, Ni Y, Rashid NU, Kim MJ, Adar S, Zhang Z, Wang T, Winter D, Keefe D, Birney E, Iyer VR, Lieb JD, Crawford GE, Li G, Sandhu KS, Zheng M, Wang P, Luo OJ, Shahab A, Fullwood MJ, Ruan X, Ruan Y, Myers RM, Pauli F, Williams BA, Gertz J, Marinov GK, Reddy TE, Vielmetter J, Partridge E, Trout D, Varley KE, Gasper C, Bansal A, Pepke S, Jain P, Amrhein H, Bowling KM, Anaya M, Cross MK, King B, Muratet MA, Antoshechkin I, Newberry KM, McCue K, Nesmith AS, Fisher-Aylor KI, Pusey B, DeSalvo G, Parker SL, Balasubramanian S, Davis NS, Meadows SK, Eggleston T, Gunter C, Newberry J, Levy SE, Absher DM, Mortazavi A, Wong WH, Wold B, Blow MJ, Visel A, Pennachio LA, Elnitski L, Margulies EH, Parker SC, Petrykowska HM, Abyzov A, Aken B, Barrell D, Barson G, Berry A, Bignell A, Boychenko V, Bussotti G, Chrast J, Davidson C, Derrien T, Despacio-Reyes G, Diekhans M, Ezkurdia I, Frankish A, Gilbert J, Gonzalez JM, Griffiths E, Harte R, Hendrix DA, Howald C, Hunt T, Jungreis I, Kay M, Khurana E, Kokocinski F, Leng J, Lin MF, Loveland J, Lu Z, Manthravadi D, Mariotti M, Mudge J, Mukherjee G, Notredame C, Pei B, Rodriguez JM, Saunders G, Sboner A, Searle S, Sisu C, Snow C, Steward C, Tanzer A, Tapanari E, Tress ML, van Baren MJ, Walters N, Washietl S, Wilming L, Zadissa A, Zhang Z, Brent M, Haussler D, Kellis M, Valencia A, Gerstein M, Reymond A, Guigó R, Harrow J, Hubbard TJ, Landt SG, Frietze S, Abyzov A, Addleman N, Alexander RP, Auerbach RK, Balasubramanian S, Bettinger K, Bhardwaj N, Boyle AP, Cao AR, Cayting P, Charos A, Cheng Y, Cheng C, Eastman C, Euskirchen G, Fleming JD, Grubert F, Habegger L, Hariharan M, Harmanci A, Iyengar S, Jin VX, Karczewski KJ, Kasowski M, Lacroute P, Lam H, Lamarre-Vincent N, Leng J, Lian J, Lindahl-Allen M, Min R, Miotto B, Monahan H, Moqtaderi Z, Mu XJ, O'Geen H, Ouyang Z, Patacsil D, Pei B, Raha D, Ramirez L, Reed B, Rozowsky J, Sboner A, Shi M, Sisu C, Slifer T, Witt H, Wu L, Xu X, Yan KK, Yang X, Yip KY, Zhang Z, Struhl K, Weissman SM, Gerstein M, Farnham PJ, Snyder M, Tenenbaum SA, Penalva LO, Doyle F, Karmakar S, Landt SG, Bhanvadia RR, Choudhury A, Domanus M, Ma L, Moran J, Patacsil D, Slifer T, Victorsen A, Yang X, Snyder M, Auer T, Centanin L, Eichenlaub M, Gruhl F, Heermann S, Hoeckendorf B, Inoue D, Kellner T, Kirchmaier S, Mueller C, Reinhardt R, Schertel L, Schneider S, Sinn R, Wittbrodt B, Wittbrodt J, Weng Z, Whitfield TW, Wang J, Collins PJ, Aldred SF, Trinklein ND, Partridge EC, Myers RM, Dekker J, Jain G, Lajoie BR, Sanyal A, Balasundaram G, Bates DL, Byron R, Canfield TK, Diegel MJ, Dunn D, Ebersol AK, Frum T, Garg K, Gist E, Hansen R, Boatman L, Haugen E, Humbert R, Jain G, Johnson AK, Johnson EM, Kutyavin TV, Lajoie BR, Lee K, Lotakis D, Maurano MT, Neph SJ, Neri FV, Nguyen ED, Qu H, Reynolds AP, Roach V, Rynes E, Sabo P, Sanchez ME, Sandstrom RS, Sanyal A, Shafer AO, Stergachis AB, Thomas S, Thurman RE, Vernot B, Vierstra J, Vong S, Wang H, Weaver MA, Yan Y, Zhang M, Akey JM, Bender M, Dorschner MO, Groudine M, MacCoss MJ, Navas P, Stamatoyannopoulos G, Kaul R, Dekker J, Stamatoyannopoulos JA, Dunham I, Beal K, Brazma A, Flicek P, Herrero J, Johnson N, Keefe D, Lukk M, Luscombe NM, Sobral D, Vaquerizas JM, Wilder SP, Batzoglou S, Sidow A, Hussami N, Kyriazopoulou-Panagiotopoulou S, Libbrecht MW, Schaub MA, Kundaje A, Hardison RC, Miller W, Giardine B, Harris RS, Wu W, Bickel PJ, Banfai B, Boley NP, Brown JB, Huang H, Li Q, Li JJ, Noble WS, Bilmes JA, Buske OJ, Hoffman MM, Sahu AD, Kharchenko PV, Park PJ, Baker D, Taylor J, Weng Z, Iyer S, Dong X, Greven M, Lin X, Wang J, Xi HS, Zhuang J, Gerstein M, Alexander RP, Balasubramanian S, Cheng C, Harmanci A, Lochovsky L, Min R, Mu XJ, Rozowsky J, Yan KK, Yip KY, Birney E., and Miotto, Benoit

Subjects
Encyclopedias as Topic, [SDV]Life Sciences [q-bio], DNA Footprinting, Genoma humà, Binding Sites/genetics, Histones/chemistry/metabolism, 0302 clinical medicine, Exons/genetics, ddc:576.5, 0303 health sciences, Multidisciplinary, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, [SDV.BIBS] Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], DNA-Binding Proteins/metabolism, region, Chemistry, Genetic Predisposition to Disease/genetics, Genomics, Polymorphism, Single Nucleotide/genetics, [SDV.BIBS]Life Sciences [q-bio]/Quantitative Methods [q-bio.QM], Neoplasms/genetics, Chromatin, Cell biology, in vivo, Genetic Variation/genetics, 030220 oncology & carcinogenesis, Deoxyribonuclease I/metabolism, Proteins/genetics, transcription factor-binding, chromosome conformation capture, DNA Methylation/genetics, Chromosomes, Human/genetics/metabolism, Chromatin Immunoprecipitation, Mammals/genetics, DNA/genetics, determinant, Article, 03 medical and health sciences, map, Animals, Humans, Transcription Factors/metabolism, Alleles, mouse, 030304 developmental biology, Transcription, Genetic/genetics, Chromatin/genetics/metabolism, Sequence Analysis, RNA, human cell, Molecular Sequence Annotation, Regulatory Sequences, Nucleic Acid/genetics, Promoter Regions, Genetic/genetics, DNA binding site, Genòmica, Genome, Human/genetics, chromatin, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Genètica, Genome-Wide Association Study
Abstract

The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research. The Consortium is funded by grants from the NHGRI as follows: production grants: U54HG004570 (B. E. Bernstein); U01HG004695 (E. Birney); U54HG004563 (G. E. Crawford); U54HG004557 (T. R. Gingeras); U54HG004555 (T. J. Hubbard); U41HG004568 /n(W. J. Kent); U54HG004576 (R. M. Myers); U54HG004558 (M. Snyder);/nU54HG004592 (J. A. Stamatoyannopoulos). Pilot grants: R01HG003143 (J. Dekker); RC2HG005591 and R01HG003700 (M. C. Giddings); R01HG004456-03 (Y. Ruan); U01HG004571 (S. A. Tenenbaum); U01HG004561 (Z. Weng); RC2HG005679 (K. P. White). This project was supported in part by American Recovery and/nReinvestment Act (ARRA) funds from the NHGRI through grants U54HG004570, U54HG004563, U41HG004568, U54HG004592, R01HG003143, RC2HG005591,R01HG003541, U01HG004561, RC2HG005679andR01HG003988(L. Pennacchio). In addition, work from NHGRI Groups was supported by the Intramural Research/nProgram of the NHGRI (L. Elnitski, ZIAHG200323; E. H. Margulies, ZIAHG200341). Research in the Pennachio laboratory was performed at Lawrence Berkeley National Laboratory and at the United States Department of Energy Joint Genome Institute, Department of Energy Contract DE-AC02-05CH11231, University of California.

Published
2012

28. Comparison of hyperthermia and adrenaline to enhance the intratumoral accumulation of cisplatin in a murine model of peritoneal carcinomatosis

Author

Patrick Rat, Hervé Tixier, François Radais, Delphine Delroeux, François Ghiringhelli, Sylvain Ladoire, Olivier Facy, Pablo Ortega-Deballon, Bruno Chauffert, Lipides - Nutrition - Cancer (U866) (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon (ENSBANA), Service de Chirurgie Digestive, Cancérologique, Générale, Endocrinienne et Urgences (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Chirurgie Digestive [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), This paper was supported by grants from the French National League against Cancer (Committees of Saône et Loire, Nièvre, and Côte d'Or)., BMC, Ed., Service de chirurgie digestive et cancérologie, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Lipides - Nutrition - Cancer (U866) ( LNC ), Université de Bourgogne ( UB ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Ecole Nationale Supérieure de Biologie Appliquée à la Nutrition et à l'Alimentation de Dijon ( ENSBANA ), Service de chirurgie digestive [Besançon], Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Jean Minjoz, Service d'oncologie médicale, and CHU Amiens-Picardie

Subjects
MESH : Hyperthermia, Induced, MESH : Rats, Inbred Strains, Cancer Research, Pathology, Pharmacology, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, Peritoneal Neoplasm, 0302 clinical medicine, MESH : Tumor Cells, Cultured, Tumor Cells, Cultured, Medicine, MESH: Peritoneal Neoplasms, MESH : Female, MESH: Animals, Peritoneal Neoplasms, Ovarian Neoplasms, MESH : Cell Survival, 0303 health sciences, MESH : Rats, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, MESH: Rats, Inbred Strains, 3. Good health, MESH : Antineoplastic Agents, MESH: Ovarian Neoplasms, Epinephrine, Oncology, MESH: Cell Survival, 030220 oncology & carcinogenesis, Female, medicine.drug, Hyperthermia, medicine.medical_specialty, MESH: Rats, Cell Survival, MESH: Epinephrine, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, lcsh:RC254-282, MESH : Cisplatin, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, MESH : Peritoneal Neoplasms, In vivo, Animals, Humans, MESH: Tumor Cells, Cultured, MESH: Hyperthermia, Induced, 030304 developmental biology, Cisplatin, MESH: Humans, MESH : Ovarian Neoplasms, business.industry, Research, MESH : Humans, Rats, Inbred Strains, Hyperthermia, Induced, medicine.disease, MESH : Disease Models, Animal, Rats, Disease Models, Animal, MESH: Cisplatin, Apoptosis, MESH : Epinephrine, Cancer cell, MESH: Antineoplastic Agents, MESH : Animals, MESH: Disease Models, Animal, business, Ovarian cancer, MESH: Female
Abstract

Background The best method to deliver intraperitoneal chemotherapy (IPC) for peritoneal carcinomatosis from ovarian cancer is not well defined. The aim of this study was to assess the ability of hyperthermia and adrenaline to enhance the intratumoral accumulation of cisplatin in a rat model of peritoneal carcinomatosis. Methods Four groups of 5 BDIX rats with ovarian peritoneal carcinomatosis underwent IPC with 30 mg/l of cisplatin according to the following conditions: normothermia at 37° for 1 or 2 hours, hyperthermia at 42°C for 1 hour or normothermia at 37°C for 2 hours with 2 mg/l adrenaline. Tissue platinum content was measured by atomic absorption spectroscopy. The effect of hyperthermia, adrenaline and the duration of exposure to the drug was measured in vivo (tissue concentration of platinum in tumor, abdominal and extra abdominal tissues) and in vitro (cytotoxicity on human ovarian cancer cells). Results In vitro, hyperthermia and longer exposure enhanced the accumulation and the cytotoxic effect of cisplatin on cancer cells. In vivo, only the 2 hours treatment with adrenaline resulted in increased platinum concentrations. The rats treated with adrenaline showed significantly lower concentrations of cisplatin in extra peritoneal tissues than those treated with hyperthermia. Conclusion Adrenaline is more effective than hyperthermia in order to enhance the intratumoral concentration of cisplatin in rats with peritoneal carcinomatosis from ovarian origin. It may also decrease the systemic absorption of the drug.

Published
2011

29. Comparison of the Effects of Two Herbicides and an Insecticide on Tropical Freshwater Plankton in Microcosms

Author

Philippe Cecchi, Laurence Amalric, Christophe Leboulanger, G. Sarazin, Agnès Bouchez, Marc Bouvy, Marc Pagano, Claire Carré, Ecosystèmes lagunaires : organisation biologique et fonctionnement (ECOLAG), Université Montpellier 2 - Sciences et Techniques (UM2)-Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de géochimie des Eaux (LGE), Université Paris Diderot - Paris 7 (UPD7)-Institut de Physique du Globe de Paris, Bureau de Recherches Géologiques et Minières (BRGM) (BRGM), Centre Alpin de Recherche sur les Réseaux Trophiques et Ecosystèmes Limniques (CARRTEL), Institut National de la Recherche Agronomique (INRA)-Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry]), Cyanobactéries des milieux aquatiques tropicaux peu profonds. Rôles et contrôles (CYROCO), This paper is a contribution to the ECOMET project, funded by the French Ministry of Ecology, Energy, Sustainable Development, and Sea (MEEDDM), grant no. CV070000783. The authors would like to thank the Forestry and Agriculture Office at Mamoudzou (DAF Mayotte) and SOGEA-Mayotte for their help with fieldwork. We are grateful to the staff of the Gite du Mont Combani for their support during our stay. Anonymous referees are acknowledged for improvement of an earlier version of the manuscript., and Université Savoie Mont Blanc (USMB [Université de Savoie] [Université de Chambéry])-Institut National de la Recherche Agronomique (INRA)

Subjects
Paraquat, 0106 biological sciences, Insecticides, Food Chain, Health, Toxicology and Mutagenesis, [SDU.STU]Sciences of the Universe [physics]/Earth Sciences, 010501 environmental sciences, Biology, 01 natural sciences, Zooplankton, Fenitrothion, chemistry.chemical_compound, Phytoplankton, Animals, Biomass, Mozambique, 0105 earth and related environmental sciences, 2. Zero hunger, Herbicides, 010604 marine biology & hydrobiology, fungi, General Medicine, Bacterioplankton, Plankton, Pesticide, environmental monitoring/analysis, Pollution, [SDE.ES]Environmental Sciences/Environmental and Society, 6. Clean water, chemistry, 13. Climate action, Diuron, Environmental chemistry, environmental sciences and ecology, Microcosm, natural plankton communities, tropical freshwater reservoir, Water Pollutants, Chemical, Environmental Monitoring, toxicology
Abstract

International audience; Natural plankton communities from a tropical freshwater reservoir (Combani Reservoir, Mayotte Island, Mozambique Channel) were exposed, in 20-l nutrient-enriched microcosms, to two nominal concentrations of three pesticides: the herbicides diuron (2.2 and 11 mu g/l) and paraquat (10 and 40.5 mu g/l) and the insecticide fenitrothion (10 and 100 mu g/l), commonly used in the tropics for agriculture and disease vector control. Bacterioplankton, phytoplankton, and zooplankton communities were monitored for 5 days after exposure, and the concentrations of toxicant and major nutrients were measured. Bacterioplankton growth was noticeable in all systems and was slightly affected by pesticide at any concentration. A transitory increase in thymidine-based bacterial production was observed in diuron- and fenitrothion-treated microcosms, followed by a marked decrease in all microcosms after 5 days. The functional diversity of bacterioplankton, evaluated using BIOLOG ECO (R) microplates, was reduced by exposure to the highest pesticide concentrations. Phytoplankton was affected by pesticides in different ways. Chlorophyll biomass and biovolumes were increased by diuron addition and decreased by paraquat, whereas fenitrothion-treated microcosms remained unaffected relative to controls. Phytoplankton taxonomic diversity was decreased by paraquat and high doses of fenitrothion but was unaffected by addition of diuron. The decrease in diversity was due to a reduction in the number of species, whereas the density of small cells increased, especially after addition of paraquat. Heterotrophic flagellates were sensitive to paraquat and to the highest diuron concentration; a reduction in biomass of up to 90% was observed for 40.5 mu g/l paraquat. Zooplankton, dominated by Thermocyclops decipiens and Diaphanosoma excisum, was slightly sensitive to diuron, and very sensitive to paraquat. High concentrations of the insecticide fenitrothion were effective only on young stages. The potential direct and indirect effects of pesticide contamination on such a simplified plankton food web, typical of newly constructed reservoirs, appear to differ significantly depending on the biological compartment considered. The overall sensitivity of tropical plankton is comparable to the sensitivity for temperate systems, and direct and indirect effects appeared rapidly, within 5 days of exposure.

Published
2011

30. Mus spretus SEG/Pas mice resist virulent Yersinia pestis, under multigenic control

Author

C. Fayolle, Elisabeth Carniel, Marek Szatanik, Geneviève Milon, Charlène Blanchet, Jean-Jacques Panthier, Xavier Montagutelli, Jean Jaubert, Génétique Fonctionnelle de la Souris, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Yersinia, Institut Pasteur [Paris] (IP), Immunophysiologie et Parasitisme Intracellulaire, CB is a recipient of a DGA (Délégation Générale pour l’Armement) fellowship. This work was supported by a grant from Aventis Pharma (Sanofi-Aventis group) and Bayer Pharma as part of a multi-organism call for proposal. The Mouse functional Genetics Unit is supported by Merck Serono., We thank Jean-Louis Guénet for his constant interest and challenging discussions. We are grateful to Colin Crist for critical reading and suggestions on the paper, to Isabelle Lanctin for careful breeding of the SEG/Pas colony, and to the CNG (Centre National de Génotypage) for the SNP genotyping of BC mice., Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), and Institut Pasteur [Paris]

Subjects
Male, Yersinia pestis, Mus spretus, Quantitative Trait Loci, Immunology, MESH: Yersinia pestis, Virulence, Quantitative trait locus, Mice, 03 medical and health sciences, Species Specificity, Genetics, Animals, MESH: Species Specificity, MESH: Animals, Allele, MESH: Mice, Genetics (clinical), 030304 developmental biology, 0303 health sciences, [SDV.GEN]Life Sciences [q-bio]/Genetics, biology, 030306 microbiology, Wild type, biology.organism_classification, Phenotype, Immunity, Innate, MESH: Male, MESH: Quantitative Trait Loci, 3. Good health, Backcrossing, Female, MESH: Immunity, Innate, MESH: Female
Abstract

International audience; Laboratory mice are well known to be highly susceptible to virulent strains of Yersinia pestis in experimental models of bubonic plague. We have found that Mus spretus-derived SEG/Pas (SEG) mice are exceptionally resistant to virulent CO92 and 6/69 wild type strains. Upon subcutaneous injection of 10(2) colony-forming units (CFU), 90% of females and 68% of males survived, compared with only an 8% survival rate for both male and female C57BL/6 mice. Furthermore, half of the SEG mice survived a challenge of up to 10(7) CFU. The time required for mortality was similar between B6 and SEG, suggesting that survival is dependent on early rather than late processes. The analysis of 322 backcross mice identified three significant quantitative trait loci (QTLs) on chromosomes 3, 4 and 6, with dominant SEG protective alleles. Each QTL increased the survival rate by approximately 20%. The three QTLs function additively, thereby accounting for 67% of the difference between the parental phenotypes. Mice heterozygous for the three QTLs were just as resistant as SEG mice to Y. pestis challenge. The SEG strain therefore offers an invaluable opportunity to unravel mechanisms and underlying genetic factors of resistance against Y. pestis infection.

Published
2011

31. Malaria risk in Corsica, former hot spot of malaria in France

Author

Gilbert Le Goff, Céline Toty, Hélène Barré, Daniel Couret, Nil Rahola, Didier Fontenille, Isabelle Larget-Thiery, Caractérisation et contrôle des populations de vecteurs, Institut de Recherche pour le Développement (IRD), Direction de la Solidarité et de la Santé de Corse et de Corse-du-Sud, Sciences pour l'environnement (SPE), Centre National de la Recherche Scientifique (CNRS)-Université Pascal Paoli (UPP), Centre de Production et Infection des Anophèles (plateforme) - Center for the Production and Infection of Anopheles (platform) (CEPIA), Institut Pasteur [Paris], The paper is catalogued by the EDEN Steering Committee as EDEN 232 http://www.eden-fp6project.net/., Université Pascal Paoli (UPP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP), and Centre de Production et Infection des Anophèles (Plateforme) (CEPIA)

Subjects
Risk, Entomology, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, 030231 tropical medicine, Plasmodium vivax, Plasmodium falciparum, MESH: Malaria, Zoology, MESH: Insect Vectors, Biology, Plasmodium, Polymerase Chain Reaction, lcsh:Infectious and parasitic diseases, MESH: Anopheles, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Anopheles, parasitic diseases, medicine, Animals, Humans, MESH: Animals, lcsh:RC109-216, MESH: Plasmodium falciparum, 0303 health sciences, MESH: Humans, MESH: Risk, 030306 microbiology, Ecology, Research, Outbreak, MESH: Polymerase Chain Reaction, medicine.disease, biology.organism_classification, 3. Good health, Insect Vectors, Malaria, MESH: Plasmodium vivax, MESH: France, Infectious Diseases, Parasitology, France
Abstract

Background The prevalence of Plasmodium falciparum and Plasmodium vivax malaria was very high in Corsica just before the Second World War. The last outbreak was in 1972 and the most recent indigenous case was in 2006. Results Analysis of historical data shows that anopheline vectors were abundant. Recent surveys demonstrated that potential vectors are still present in Corsica, despite the likely disappearance of Anopheles sacharovi. Moreover, P. falciparum can develop experimentally into these mosquitoes, notably Anopheles labranchiae, which is locally abundant, and parasites are regularly introduced into the island. Discussion, Conclusions The presence of vectors, the introduction of parasites and the conducive climate raise questions about the possibility of malaria re-emerging and becoming re-established in Corsica. Analysis of historic and current parasitological and entomological data shows that the current theoretical risk of indigenous cases or malaria foci is negligible, particularly since there is very little contact between humans and Anopheles mosquitoes, Plasmodium carriers are reliably treated and there is a widespread vector control on the island.

Published
2010

32. PGC-1β: A Regulator of Mitochondrial Function with Subtle Roles in Energy Metabolism

Author

Adrienn Kis, Mark Campbell, Mohammad Bohlooly-Y, Keira Curtis, Barbara Cannon, Matej Orešič, E. Dale Abel, Vlad G. Zaha, Gema Medina-Gomez, Sheldon E. Litwin, Mercedes Jimenez-Linan, Antonio Vidal-Puig, Sihem Boudina, Kimberly T Fountain, Leonard H Storlien, Miguel López, Margaret Blount, Ping Hu, Helena M. Feldmann, Christopher J. Lelliott, Mikael Bjursell, Natasa Petrovic, Dongfang Zhang, Nadeene Parker, Maria Strömstedt, Aline Meirhaeghe, Michael Snaith, Autard, Delphine, Department of Clinical Biochemistry, University of Cambridge [UK] (CAM), AstraZeneca, The Wenner-Gren Institute, Stockholm University, Division of Cardiology, University of Utah, Division of Endocrinology, Metabolism, and Diabetes, Epidémiologie des maladies chroniques : impact des interactions gène environnement sur la santé des populations, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Technical Research Centre of Finland, VTT Technical Research Centre of Finland (VTT), The work presented in this paper was supported by grants from the British Heart Foundation, Wellcome Trust Integrative Physiology, and Diabetes Wellness Research Foundation (to AVP lab), and NIH grants RO1HL73167 and UO1HL70525 from the National Institutes of Health and the Ben and Iris Margolis Foundation (to EDA - Established Investigator of the American Heart Association). Support was from the European Union (DLARFID), the Swedish Research Council, and the Swedish Cancer Society (to BC lab).

Subjects
Male, MESH: Cold Temperature, Adipose tissue, White adipose tissue, Mitochondrion, MESH: Mice, Knockout, Mitochondria, Heart, chemistry.chemical_compound, Mice, Norepinephrine, 0302 clinical medicine, Adipose Tissue, Brown, Heart Rate, Brown adipose tissue, Body Fat Distribution, Diabetes/Endocrinology/Metabolism, MESH: Thermogenesis, MESH: Animals, Biology (General), MESH: Heart Rate, Mice, Knockout, Mammals, 0303 health sciences, MESH: Muscle, Skeletal, General Neuroscience, MESH: Energy Metabolism, Heart, Thermogenesis, Mus (Mouse), Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, MESH: Gene Expression Regulation, Mitochondria, Cold Temperature, medicine.anatomical_structure, Liver, MESH: Adipose Tissue, White, Synopsis, Female, MESH: Mitochondria, Heart, General Agricultural and Biological Sciences, Metabolic Networks and Pathways, Research Article, MESH: Electron Transport Chain Complex Proteins, medicine.medical_specialty, QH301-705.5, MESH: Mitochondria, MESH: Trans-Activators, Adipose Tissue, White, Biology, MESH: Diet, Atherogenic, MESH: Adipose Tissue, Brown, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, Adrenergic Agents, Internal medicine, MESH: Norepinephrine, medicine, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, MESH: Body Fat Distribution, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Muscle, Skeletal, MESH: Mice, 030304 developmental biology, Soleus muscle, General Immunology and Microbiology, Triglyceride, Body Weight, medicine.disease, MESH: Adrenergic Agents, MESH: Male, MESH: Body Weight, MESH: Heart, Endocrinology, chemistry, Electron Transport Chain Complex Proteins, Gene Expression Regulation, MESH: Metabolic Networks and Pathways, Trans-Activators, Diet, Atherogenic, Steatosis, Energy Metabolism, MESH: Female, 030217 neurology & neurosurgery, Transcription Factors, MESH: Liver
Abstract

The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1β (PGC-1β) has been implicated in important metabolic processes. A mouse lacking PGC-1β (PGC1βKO) was generated and phenotyped using physiological, molecular, and bioinformatic approaches. PGC1βKO mice are generally viable and metabolically healthy. Using systems biology, we identified a general defect in the expression of genes involved in mitochondrial function and, specifically, the electron transport chain. This defect correlated with reduced mitochondrial volume fraction in soleus muscle and heart, but not brown adipose tissue (BAT). Under ambient temperature conditions, PGC-1β ablation was partially compensated by up-regulation of PGC-1α in BAT and white adipose tissue (WAT) that lead to increased thermogenesis, reduced body weight, and reduced fat mass. Despite their decreased fat mass, PGC1βKO mice had hypertrophic adipocytes in WAT. The thermogenic role of PGC-1β was identified in thermoneutral and cold-adapted conditions by inadequate responses to norepinephrine injection. Furthermore, PGC1βKO hearts showed a blunted chronotropic response to dobutamine stimulation, and isolated soleus muscle fibres from PGC1βKO mice have impaired mitochondrial function. Lack of PGC-1β also impaired hepatic lipid metabolism in response to acute high fat dietary loads, resulting in hepatic steatosis and reduced lipoprotein-associated triglyceride and cholesterol content. Altogether, our data suggest that PGC-1β plays a general role in controlling basal mitochondrial function and also participates in tissue-specific adaptive responses during metabolic stress., The authors conduct an in-depth analysis of a PGC-1β knockout mouse; these animals posses specific defects in basal mitochondrial function and adaptation to metabolic stress.

Published
2006

33. Peroxisome proliferator-activated receptor-α activation as a mechanism of preventive neuroprotection induced by chronic fenofibrate treatment

Author

Olivier Pétrault, Bernard Dupuis, Isabelle Six, Régis Bordet, Patrick Gelé, Christophe Furman, Bart Staels, Dominique Deplanque, Roméo Cecchelli, Patrick Duriez, Muriel Bouly, Didier Leys, Jean-Charles Fruchart, Stéphane Nion, Université Lille 2 - Faculté de Médecine, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Récepteurs nucléaires, lipoprotéines et athérosclérose, Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Réseau International des Instituts Pasteur (RIIP), Université d'Artois (UA), Laboratoire de Physiopathologie de la Barrière Hémato-Encéphalique (LBHE), P.G. was supported by a grant from 'Conseil Régional Nord Pas de Calais et Centre Hospitalier Régional et Universitaire de Lille. ' This work was supported by grants from ' Génopole Lille Nord-Pas de Calais '(#01360124) and Institut National de la Santé et de la Recherche Médicale (CReS4CR02F)., and We thank Alexandra Tavernier-Sommerville for her assistance with the English version of this paper.

Subjects
Middle Cerebral Artery, Mouse, Nitric Oxide Synthase Type II, Receptors, Cytoplasmic and Nuclear, Peroxisome proliferator-activated receptor, medicine.disease_cause, Rats, Inbred WKY, Mice, 0302 clinical medicine, Fenofibrate, Mice, Knockout, chemistry.chemical_classification, 0303 health sciences, biology, General Neuroscience, Infarction, Middle Cerebral Artery, Cerebral Infarction, Intercellular Adhesion Molecule-1, Neuroprotection, Vasodilation, Nitric oxide synthase, Stroke, Neuroprotective Agents, Cerebrovascular Circulation, Middle cerebral artery, medicine.symptom, medicine.drug, PPAR-α, medicine.medical_specialty, Adhesion proteins, Nitric Oxide Synthase Type III, Development/Plasticity/Repair, Ischemia, Vascular Cell Adhesion Molecule-1, Mice, Transgenic, Inflammation, Time, 03 medical and health sciences, Apolipoproteins E, medicine.artery, Internal medicine, medicine, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, 030304 developmental biology, business.industry, Prevention, medicine.disease, Rats, Mice, Inbred C57BL, Disease Models, Animal, Endocrinology, chemistry, Oxidative stress, biology.protein, Nitric Oxide Synthase, business, 030217 neurology & neurosurgery, Transcription Factors
Abstract

International audience; The treatment of ischemic strokes is limited to the prevention of cerebrovascular risk factors and to the modulation of the coagulation cascade during the acute phase. Anew therapeutic strategy could be to preventively protect the brain against noxious biological reactions induced by cerebral ischemia such as oxidative stress and inflammation to minimize their neurological consequences. Here, we show that a peroxisome proliferator-activated receptor (PPAR-α) activator, fenofibrate, protects against cerebral injury by anti-oxidant and antiinflammatory mechanisms. A 14 d preventive treatment with fenofibrate reduces susceptibility to stroke in apolipoprotein E-deficient mice as well as decreases cerebral infarct volume in C57BL/6 wild-type mice. The neuroprotective effect of fenofibrate is completely absent in PPAR-α-deficient mice, suggesting that PPAR-α activation is involved as a mechanism of the protection against cerebral injury. Furthermore, this neuroprotective effect appears independently of any improvement in plasma lipids or glycemia and is associated with (1) an improvement in middle cerebral artery sensitivity to endothelium-dependent relaxation unrelated to an increase in nitric oxide synthase (NOS) type III expression, (2) a decrease in cerebral oxidative stress depending on the increase in numerous antioxidant enzyme activities, and (3) the prevention of ischemia-induced expression of vascular cell adhesion molecule-1 and intercellular adhesion molecule-1 in cerebral vessels without any change in NOS II expression. These data demonstrate that PPAR-α could be a new pharmacological target to preventively reduce the deleterious neurological consequences of stroke in mice and suggest that PPAR-α activators could preventively decrease the severity of stroke in humans.

Published
2003

34. CCKA, but not CCKB, agonists suppress the hyperlocomotion induced by endogenous enkephalins, protected from enzymatic degradation by systemic RB 101

Author

Bernard P. Roques, Valérie Daugé, P. J. Corringer, Pharmacochimie moléculaire et structurale, Institut des sciences du Médicament -Toxicologie - Chimie - Environnement (IFR71), Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), We wish to thank Dr. A. Beaumont and Dr.J.Vierek for the stylistic revision of the paper, and C. Dupuis for her assistance in drafting it. We are grateful to S.Turcaud and P. Coric for the synthesis of RB 101., Cova Rodrigues, Ana, Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), and Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Paris Descartes - Paris 5 (UPD5)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Male, Enkephalin, Narcotic Antagonists, [SDV]Life Sciences [q-bio], Clinical Biochemistry, RB-101, Devazepide, Inhibitor of enkephalin degradation, MESH: Amino Acid Sequence, Toxicology, Biochemistry, MESH: Benzodiazepinones, Behavioral Neuroscience, Mice, 0302 clinical medicine, Interactions between CCK and enkephalins, MESH: Enkephalins, MESH: Animals, Disulfides, Enzyme Inhibitors, MESH: Cholecystokinin, MESH: Peptide Fragments, MESH: Devazepide, 0303 health sciences, Benzodiazepinones, MESH: Receptors, Cholecystokinin, Chemistry, digestive, oral, and skin physiology, Enkephalins, [SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences, Naltrexone, CCKA and CCKB agonists, MESH: Motor Activity, [SDV] Life Sciences [q-bio], [SDV.SP] Life Sciences [q-bio]/Pharmaceutical sciences, MESH: Enzyme Inhibitors, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, MESH: Naltrexone, MESH: Narcotic Antagonists, Cholecystokinin, hormones, hormone substitutes, and hormone antagonists, medicine.drug, Agonist, Locomotor activity, medicine.medical_specialty, medicine.drug_class, Phenylalanine, Molecular Sequence Data, Motor Activity, 03 medical and health sciences, MESH: Phenylalanine, Naltrindole, Internal medicine, medicine, Animals, MESH: Disulfides, Amino Acid Sequence, Opioid peptide, MESH: Mice, Biological Psychiatry, 030304 developmental biology, Pharmacology, MESH: Molecular Sequence Data, Antagonist, Peptide Fragments, MESH: Male, Endocrinology, [SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Receptors, Cholecystokinin, Physiological agonism and antagonism, 030217 neurology & neurosurgery
Abstract

International audience; Interactions between CCKergic and enkephalinergic systems were studied in mice using behavioral responses measured in Animex. The hyperlocomotion induced by 5 mg/kg of RB 101, a mixed inhibitor of enkephalin-degrading enzymes able to cross the blood-brain barrier, was previously shown to be mediated by delta-opioid receptor stimulation. The IP administration of a CCKA agonist, Boc-Tyr-Lys-(CONH-o-tolyl)-Asp-Phe-NH2 (0.1, 1, 10 micrograms/kg), suppressed the hyperlocomotion produced by IV injection of 5 mg/kg of RB 101. The effect of the CCKA agonist was suppressed by a selective CCKA antagonist, devazepide, injected IP at doses of 20 and 200 micrograms/kg and was potentiated by the selective delta-opioid antagonist naltrindole at the doses of 0.03 mg/kg. IP injection of the selective CCKB agonist BC 264 (0.1-1 mg/kg) did not modify the RB 101-induced hyperlocomotor effect. These results reinforce the observed physiological antagonism between the endogenous CCK and opioid systems but are at variance with the responses measured in stressful conditions. It is concluded that CCKA, but not CCKB, receptor activation counteracts the opioid-related hyperlocomotion.

Published
1995

35. Regional trends and drivers of the global methane budget

Author

Naveen Chandra, Akihiko Ito, Philippe Ciais, Peter A. Raymond, Jurek Müller, Ann R. Stavert, Joe R. Melton, Marielle Saunois, Phillipe Bousquet, Adrian Gustafson, Yosuke Niwa, Robert B. Jackson, Shushi Peng, Qianlai Zhuang, Hanqin Tian, Aki Tsuruta, George H. Allen, Benjamin Poulter, Joe McNorton, Bo Zheng, Yi Yin, Prabir K. Patra, Thomas Kleinen, Pierre Regnier, Peter Bergamaschi, Ronny Lauerwald, Shamil Maksyutov, Misa Ishizawa, Arjo Segers, William J. Riley, Josep G. Canadell, Zhen Zhang, Laboratoire des Sciences du Climat et de l'Environnement [Gif-sur-Yvette] (LSCE), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Modélisation INVerse pour les mesures atmosphériques et SATellitaires (SATINV), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Université libre de Bruxelles (ULB), This paper is the result of a collaborative international effort under the umbrella of the Global Carbon Project, a Global Research Project of Future Earth and a research partner of the World Climate Research Programme. We acknowledge primary support for the methane budget from the Gordon and Betty Moore Foundation through Grant GBMF5439 'Advancing Understanding of the Global Methane Cycle' to Stanford University (P.I. Rob Jackson, co- P.I.s Philippe Bousquet, Marielle Saunois, Josep Canadell, Gustaf Hugelius, and Ben Poulter). Josep Canadell acknowledges the support of the Australian National Environmental Science Program – Earth Systems and Climate Change. Prabir K Patra and Neveen Chandra acknowledge support from Environment Research and Technology Development Funds of the Environmental Restoration and Conservation Agency of Japan (JPMEERF20182002, JPMEERF20172001). Jurek Müller thanks for support by the Swiss National Science Foundation (#200020_172476). Peter Bergamaschi acknowledges the support of ECMWF providing computing resources under the special project 'Improve European and global CH4 and N2O flux inversions (2018-2020)'. Pierre Regnier acknowledges the support from the VERIFY project under European Union's Horizon 2020 research and innovation program grant agree-ment no. 776810. The TM5-CAMS inversions are available from https://atmos phere.copernicus.eu, Arjo Segers acknowledges the support from the Copernicus Atmosphere Monitoring Service, implemented by the European Centre for Medium-Range Weather Forecasts on be-half of the European Commission (grant no. CAMS73). William Riley acknowledges support by the US Department of Energy, Office of Science, Biological and Environmental Research, Regional and Global Climate Modeling Program through the RUBISCO Scientific Focus Area under contract DE-AC02- 05CH11231 to Lawrence Berkeley National Laboratory. The authors gratefully acknowledge those re-sponsible for the global network of atmospheric observations used in this study including Donald R Blake and Isobel Simpson, University of California Irvine, USA, Gordon Brailsford, NIWA, Cyril Crevosier, LMD, France, New Zealand, Paul Krummel and Ray Langenfelds, CSIRO, Australia, Toshinobu Machida, Yasunori Tohjima and Yukio Yoshida, NIES, Japan, Ronald Prinn, MIT, USA, Simon O’Doherty, University of Bristol, UK, Michel Ramonet, LSCE-IPSL, France, Atsushi Takizawa, JMA, Japan, Ray Weiss, Scripps Institute of Oceanography, USA and Doug Worthy, Environment Canada, Canada. We would also like to thank Lena Höglund-Isaksson, IIASA, Austria, Greet Janssens- Maenhout EC-JRC, Italy and Steven Smith, PNNL-JGCR, USA for their assistance with the anthropogenic inventory data. The authors also acknowledge the significant contribution of Goulven G. Laruelle, Department Geoscience, Environment & Society, Université Libre de Bruxelles, Brussels, Belgium who, with P. Regnier, developed the re-gionally distributed estuarine flux data set., and European Project: 776810,H2020,H2020-SC5-2017-OneStageB,VERIFY(2018)

Subjects
China, Municipal solid waste, Livestock, 010504 meteorology & atmospheric sciences, methane emissions, Oceans and Seas, 010501 environmental sciences, 7. Clean energy, 01 natural sciences, Methane, 12. Responsible consumption, bottom-up, Atmosphere, chemistry.chemical_compound, Enteric fermentation, Environmental protection, source sectors, Environmental Chemistry, Animals, [SDU.ENVI]Sciences of the Universe [physics]/Continental interfaces, environment, ComputingMilieux_MISCELLANEOUS, 0105 earth and related environmental sciences, General Environmental Science, [SDU.OCEAN]Sciences of the Universe [physics]/Ocean, Atmosphere, Global and Planetary Change, regional, Ecology, business.industry, Coal mining, Biological Sciences, Climate Action, natural emissions, Carbon project, chemistry, 13. Climate action, Greenhouse gas, top-down, Environmental science, anthropogenic emissions, business, Environmental Sciences
Abstract

The ongoing development of the Global Carbon Project (GCP) global methane (CH4 ) budget shows a continuation of increasing CH4 emissions and CH4 accumulation in the atmosphere during 2000-2017. Here, we decompose the global budget into 19 regions (18land and 1 oceanic) and five key source sectors to spatially attribute the observed global trends. A comparison of top-down (TD) (atmospheric and transport model-based) and bottom-up (BU) (inventory- and process model-based) CH4 emission estimates demonstrates robust temporal trends with CH4 emissions increasing in 16 of the 19 regions. Five regions-China, Southeast Asia, USA, South Asia, and Brazil-account for >40% of the global total emissions (their anthropogenic and natural sources together totaling >270Tg CH4 yr-1 in 2008-2017). Two of these regions, China and South Asia, emit predominantly anthropogenic emissions (>75%) and together emit more than 25% of global anthropogenic emissions. China and the Middle East show the largest increases in total emission rates over the 2000 to 2017 period with regional emissions increasing by >20%. In contrast, Europe and Korea and Japan show a steady decline in CH4 emission rates, with total emissions decreasing by ~10% between 2000 and 2017. Coal mining, waste (predominantly solid waste disposal) and livestock (especially enteric fermentation) are dominant drivers of observed emissions increases while declines appear driven by a combination of waste and fossil emission reductions. As such, together these sectors present the greatest risks of further increasing the atmospheric CH4 burden and the greatest opportunities for greenhouse gas abatement.

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36. Adult mosquito predation and potential impact on the sterile insect technique

Author

Bimbilé Somda, Nanwintoum, Maïga, Hamidou, Mamai, Wadaka, Bakhoum, Thierno, Wallner, Thomas, Poda, Serge, Yamada, Hanano, Bimbilé Somda, Nanwintoum Séverin, Poda, Serge Bèwadéyir, Bouyer, Jérémy, Insect Pest Control Laboratory (IPC laboratory), Food and Agriculture Organization of the United Nations [Rome, Italie] (FAO)-International Atomic Energy Agency [Vienna] (IAEA), Institut de Recherche en Sciences de la Santé Bobo Dioulasso (INSSA), Université Polytechnique Nazi Boni Bobo-Dioulasso (UNB), Université Norbert ZONGO de Koudougou, Institut de Recherche Agricole pour le Développement [Yaoundé] (IRAD), Animal, Santé, Territoires, Risques et Ecosystèmes (UMR ASTRE), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Département Systèmes Biologiques (Cirad-BIOS), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), The research presented in this paper was partially funded by the United States of America under the grant to the IAEA entitled: Surge expansion for the sterile insect technique to control mosquito populations that transmit the Zika virus and by the European Research Council under the European Union's Horizon 2020 research and innovation program (grant agreement no. 682387-REVOLINC)., and European Project: 682387,REVOLINC

Subjects
[SDV.BIO]Life Sciences [q-bio]/Biotechnology, Mosquito Control, Mantodea, Aedes aegypti, Aedes, Animals, Traitement, Multidisciplinary, Lutte anti-insecte, fungi, Lâcher d'insectes stériles, Lizards, Aedes albopictus, Anopheles arabiensis, Predatory Behavior, Prédation, Irradiation, L20 - Écologie animale, L72 - Organismes nuisibles des animaux
Abstract

The sterile insect technique is a promising environmentally friendly method for mosquito control. This technique involves releasing laboratory-produced sterile males into a target field site, and its effectiveness may be affected by the extent of adult mosquito predation. Sterile males undergo several treatments. Therefore, it is vital to understand which treatments are essential in minimizing risks to predation once released. The present study investigates the predation propensity of four mantis species (Phyllocrania paradoxa, Hymenopus coronatus, Blepharopsis mendica, Deroplatys desiccata) and two gecko species (Phelsuma standingi, P. laticauda) on adult Aedes aegypti, Ae. albopictus and Anopheles arabiensis mosquitoes in a laboratory setting. First, any inherent predation preferences regarding mosquito species and sex were evaluated. Subsequently, the effects of chilling, marking, and irradiation, on predation rates were assessed. The selected predators effectively preyed on all mosquito species regardless of the treatment. Predation propensity varied over days for the same individuals and between predator individuals. Overall, there was no impact of laboratory treatments of sterile males on the relative risk of predation by the test predators, unless purposely exposed to double the required sterilizing irradiation dose. Further investigations on standardized predation trials may lead to additional quality control tools for irradiated mosquitoes.

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37. Coordinated recruitment of Spir actin nucleators and myosin V motors to Rab11 vesicle membranes

Author

Andreas T. Grasskamp, Martin Kollmar, Janine Tittel, Margaret A. Titus, Petra Schwille, Eugen Kerkhoff, Florian Chardon, Bruno Goud, Thomas Weidemann, Gilles Malherbe, Olena Pylypenko, Annette Samol-Wolf, Bruno Baron, Patrick England, Carina Ida Luise Michel, Sabine Weiss, Alistair N. Hume, Anne Houdusse, Tobias Welz, Biologie Cellulaire et Cancer, Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University Hospital Regensburg, Max-Planck-Institut für Biochemie = Max Planck Institute of Biochemistry (MPIB), Max-Planck-Gesellschaft, Max-Planck-Institut für Biophysikalische Chemie - Max Planck Institute for Biophysical Chemistry [Göttingen], Motilité structurale, Compartimentation et dynamique cellulaires (CDC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), University of Nottingham, UK (UON), Biophysique des macromolécules et leurs interactions, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), University of Minnesota [Twin Cities] (UMN), University of Minnesota System, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), This paper was supported by the following grants:Centre National de la Recherche Scientifique to Anne Houdusse, Olena Pylypenko., Deutsche Forschungsgemeinschaft SPP 1464: KO 2251/13-1 to Martin Kollmar., Bayerische Forschungsstiftung WFKMS Nr. F2 - 5121.4.3.1 ‐10c (BayGene) to Eugen Kerkhoff., Fondation de la Recherche Medicale ING20140129255 to Anne Houdusse., Agence Nationale de la Recherche ANR-13-BSV8-0019-01 to Anne Houdusse., National Science Foundation MCB-1244235 to Margaret A Titus., University of Minnesota Medical School Award, E-0915-04 to Margaret A Titus., Deutsche Forschungsgemeinschaft SPP 1464: SCHW 716/11-1, -2 to Petra Schwille., Ligue Contre le Cancer RS16/75-67 to Anne Houdusse., Fondation ARC pour la Recherche sur le Cancer SFI20121205398 to Anne Houdusse., Deutsche Forschungsgemeinschaft SPP 1464: KE 447/10-1, -2 to Eugen Kerkhoff., We acknowledge SOLEIL for provision of synchrotron radiation facilities (proposal 20141015) and we would like to thank Pierre Legrand and Beatriz Guimares for assistance in using beamline PX1. We thank Sandra Lemke, Carsten Grashoff, Yilmaz Niyaz (Zeiss) and Volker Buschmann (Picoquant) for their generous support in FLIM. We thank Mitsuo Ikebe for providing a MyoVb cDNA. We acknowledge Wikayatou Attanda and Charles Gauquelin for support in recombinant protein production. We also acknowledge Damarys Loew and Vanessa Masson (Curie Institute Protein Mass Spectrometry Platform) for the peptide fingerprint analysis of Spir-2 constructs. BG, AHo, OP, GM, FC are part of the Labex CelTisPhyBio 11-LBX-0038, which is part of the IDEX PSL (ANR-10-IDEX-0001-02 PSL)., Max Planck Institute of Biochemistry (MPIB), Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC), Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], and Centre National de la Recherche Scientifique (CNRS)-Institut Curie [Paris]-Université Pierre et Marie Curie - Paris 6 (UPMC)

Subjects
0301 basic medicine, Models, Molecular, Protein Conformation, none, [SDV]Life Sciences [q-bio], Arp2/3 complex, Microfilament, Crystallography, X-Ray, vesicle transport, Myosin head, Mice, 0302 clinical medicine, MESH: Protein Conformation, biophysics, Myosin, cell biology, structural biology, MESH: Animals, Biology (General), Actin nucleation, MESH: Protein Multimerization, General Neuroscience, Microfilament Proteins, General Medicine, Biophysics and Structural Biology, MESH: rab GTP-Binding Proteins/chemistry, Cell biology, MESH: rab GTP-Binding Proteins/metabolism, Medicine, MESH: Cytoplasmic Vesicles/metabolism, MESH: Membranes/metabolism, MESH: Models, Molecular, Research Article, Protein Binding, Myosin light-chain kinase, QH301-705.5, Science, Myosin Type V, MESH: Microfilament Proteins/chemistry, MESH: Microfilament Proteins/metabolism, macromolecular substances, Biology, General Biochemistry, Genetics and Molecular Biology, actin motor proteins, 03 medical and health sciences, MESH: Myosin Type V/metabolism, Animals, MESH: Protein Binding, Actin-binding protein, MESH: Mice, MESH: Myosin Type V/chemistry, Membranes, Spire, General Immunology and Microbiology, Cytoplasmic Vesicles, myosin V, Actin remodeling, MESH: Crystallography, X-Ray, 030104 developmental biology, rab GTP-Binding Proteins, Rab11, biology.protein, Protein Multimerization, actin nucleation, 030217 neurology & neurosurgery
Abstract

There is growing evidence for a coupling of actin assembly and myosin motor activity in cells. However, mechanisms for recruitment of actin nucleators and motors on specific membrane compartments remain unclear. Here we report how Spir actin nucleators and myosin V motors coordinate their specific membrane recruitment. The myosin V globular tail domain (MyoV-GTD) interacts directly with an evolutionarily conserved Spir sequence motif. We determined crystal structures of MyoVa-GTD bound either to the Spir-2 motif or to Rab11 and show that a Spir-2:MyoVa:Rab11 complex can form. The ternary complex architecture explains how Rab11 vesicles support coordinated F-actin nucleation and myosin force generation for vesicle transport and tethering. New insights are also provided into how myosin activation can be coupled with the generation of actin tracks. Since MyoV binds several Rab GTPases, synchronized nucleator and motor targeting could provide a common mechanism to control force generation and motility in different cellular processes. DOI: http://dx.doi.org/10.7554/eLife.17523.001

38. Isolation and sequencing of Dashli virus, a novel Sicilian-like virus in sandflies from Iran; genetic and phylogenetic evidence for the creation of one novel species within the Phlebovirus genus in the Phenuiviridae family

Author

Xavier de Lamballerie, E. Javadian, Cigdem Alkan, Nourina Rahbarian, Bulent Alten, Laurence Bichaud, Nazli Ayhan, Mehdi Badakhshan, Vahideh Moin Vaziri, Rémi N. Charrel, BUISINE, Soline, European Virus Archive goes global - EVAg - - H20202015-04-01 - 2019-03-31 - 653316 - VALID, Biology and control of vector-borne infections in Europe - EDENEXT - - EC:FP7:HEALTH2011-01-01 - 2015-06-30 - 261504 - VALID, Unité des Virus Emergents (UVE), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), Department of Parasitology and Mycology [Tehran, Iran] (School of Medicine), Shahid Beheshti University of Medical Sciences [Tehran, Iran], Department of Medical Entomology and Vector Control [Tehran, Iran] (School of Public Health), Tehran University of Medical Sciences-Institute of Public Health Research [Tehran, Iran], Cellular and Molecular Biology Research Center [Tehran, Iran] (SBU), Shahid Beheshti University of Medical Sciences [Tehran] (SBUMS), Hacettepe University = Hacettepe Üniversitesi, Hôpital de la Timone [CHU - APHM] (TIMONE), This work was supported through funds received from EU grant FP7-261504 EDENext and this paper is catalogued by the EDENext Steering Committee (http://www.edenext.eu), the European Virus Archive goes Global (EVAg) project in the European Union's Horizon 2020 research and innovation programme under grant agreement No 653316 (http://global.european- virus-archive.com/). The present article partly was supported by Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran. (Grant No: 1573) The work of RNC was done under the frame of EurNegVec (TD1303) COST Action., European Project: 653316,H2020,H2020-INFRAIA-2014-2015,EVAg(2015), European Project: 261504,EC:FP7:HEALTH,FP7-HEALTH-2010-single-stage,EDENEXT(2011), and Shahid Beheshti University-Shahid Beheshti University

Subjects
0301 basic medicine, Male, Phlebovirus, RNA viruses, Fevers, Iran, Disease Vectors, Pathology and Laboratory Medicine, Database and Informatics Methods, Phlebotomus Fever, Bunyaviruses, Medicine and Health Sciences, Sandfly Fever Sicilian Virus, Phylogeny, Data Management, Genetics, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, biology, Phylogenetic tree, lcsh:Public aspects of medicine, Phylogenetic Analysis, Gene Pool, 3. Good health, Phylogenetics, Infectious Diseases, Medical Microbiology, Viral Pathogens, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Viruses, RNA, Viral, Female, Gene pool, Pathogens, Sequence Analysis, Research Article, Computer and Information Sciences, lcsh:Arctic medicine. Tropical medicine, lcsh:RC955-962, Bioinformatics, Genome, Viral, Research and Analysis Methods, Microbiology, Virus, 03 medical and health sciences, Signs and Symptoms, Amino Acid Sequence Analysis, Diagnostic Medicine, Animals, Humans, Evolutionary Systematics, Microbial Pathogens, Taxonomy, Evolutionary Biology, Base Sequence, Population Biology, Sequence Analysis, RNA, Public Health, Environmental and Occupational Health, Organisms, Biology and Life Sciences, lcsh:RA1-1270, biology.organism_classification, Rift Valley fever virus, Sandfly, Insect Vectors, Sand Flies, Species Interactions, 030104 developmental biology, Microbial genetics, Psychodidae, Population Genetics
Abstract

Phlebotomine sandflies are vectors of phleboviruses that cause sandfly fever or meningitis with significant implications for public health. Although several strains of these viruses had been isolated in Iran in the late 1970's, there was no recent data about the present situation at the outset of this study. Entomological investigations performed in 2009 and 2011 in Iran collected 4,770 sandflies from 10 different regions. Based on morphological identification, they were sorted into 315 pools according to species, sex, trapping station and date of capture. A phlebovirus, provisionally named Dashli virus (DASHV), was isolated from one pool of Sergentomyia spp, and subsequently DASHV RNA was detected in a second pool of Phlebotomus papatasi. Genetic and phylogenetic analyses based on complete coding genomic sequences indicated that (i) DASHV is most closely related to the Iranian isolates of Sandfly fever Sicilian virus [SFSV], (ii) there is a common ancestor to DASHV, Sandfly fever Sicilian- (SFS) and SFS-like viruses isolated in Italy, India, Turkey, and Cyprus (lineage I), (iii) DASHV is more distantly related with Corfou and Toros viruses (lineage II) although common ancestry is supported with 100% bootstrap, (iii) lineage I can be subdivided into sublineage Ia including all SFSV, SFCV and SFTV except those isolated in Iran which forms sublineage Ib (DASHV). Accordingly, we suggest to approve Sandfly fever Sicilian virus species consisting of the all aforementioned viruses. Owing that most of these viruses have been identified in human patients with febrile illness, DASHV should be considered as a potential human pathogen in Iran., Author summary Phlebotomine sandflies are vectors of phleboviruses that cause sandfly fever or meningitis with significant implications for public health. Although several strains of these viruses had been isolated in Iran in the late 1970's, there was no recent data about the present situation at the outset of this study. Entomological investigations performed in 2009 and 2011 in Iran collected 4,770 sandflies from 10 different regions. A phlebovirus, provisionally named Dashli virus (DASHV), was isolated / detected in two pools. DASHV strain was isolated in cell culture and complete genome sequence was determined. Sequence analysis indicated that (i) DASHV is most closely related to the Iranian isolates of Sandfly fever Sicilian virus [SFSV], a virus that is known to cause self-resolutive incapacitating febrile illness in humans, (ii) there is a common ancestor to DASHV and all other variants of SFSV isolated in Italy, India, Turkey, and Cyprus (lineage I), (iii) DASHV is more distantly related with Corfou and Toros viruses (lineage II) although common ancestry is supported with 100% bootstrap, (iii) lineage I can be subdivided into sublineage Ia including all SFSV strains, whereas Iranian viruses are most closely related and should be individualized as DASHV (sublineage Ib). Although discovered first in the 1940's, SFSV is still listed as "tentative species" by the International Committee for Taxonomy of Viruses. Based on the results described in this study, we propose to approve Sandfly fever Sicilian virus species. Owing that most of these viruses have been identified in human patients with febrile illness, DASHV should be considered as a potential human pathogen in Iran.

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