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2. Meta‐analysis of individual‐patient data from EVAR‐1, DREAM, OVER and ACE trials comparing outcomes of endovascular or open repair for abdominal aortic aneurysm over 5 years

Author

Powell, J. T., Sweeting, M. J., Ulug, P., Blankensteijn, J. D., Lederle, F. A., Becquemin, J.‐P., Greenhalgh, R. M., Greenhalgh, R. M., Beard, J. D., Buxton, M. J., Brown, L. C., Harris, P. L., Powell, J. T., Rose, J. D. G., Russell, I. T., Sculpher, M. J., Thompson, S. G., Lilford, R.J., Bell, P. R. F., Greenhalgh, R. M., Whitaker, S.C., Poole‐Wilson, the late P.A., Ruckley, C. V., Campbell, W. B., Dean, M. R. E., Ruttley, M. S. T., Coles, E. C., Powell, J. T., Halliday, A., Gibbs, S. J., Brown, L. C., Epstein, D., Sculpher, M. J., Thompson, S. G., Hannon, R. J., Johnston, L., Bradbury, A. W., Henderson, M. J., Parvin, S. D., Shepherd, D. F. C., Greenhalgh, R. M., Mitchell, A. W., Edwards, P. R., Abbott, G. T., Higman, D. J., Vohra, A., Ashley, S., Robottom, C., Wyatt, M. G., Rose, J. D. G., Byrne, D., Edwards, R., Leiberman, D. P., McCarter, D. H., Taylor, P. R., Reidy, J. F., Wilkinson, A. R., Ettles, D. F., Clason, A. E., Leen, G. L. S., Wilson, N. V., Downes, M., Walker, S. R., Lavelle, J. M., Gough, M. J., McPherson, S., Scott, D. J. A., Kessell, D. O., Naylor, R., Sayers, R., Fishwick, N. G., Harris, P. L., Gould, D. A., Walker, M. G., Chalmers, N. C., Garnham, A., Collins, M. A., Beard, J. D., Gaines, P. A., Ashour, M. Y., Uberoi, R., Braithwaite, B., Whitaker, S. C., Davies, J. N., Travis, S., Hamilton, G., Platts, A., Shandall, A., Sullivan, B. A., Sobeh, M., Matson, M., Fox, A. D., Orme, R., Yusef, W., Doyle, T., Horrocks, M., Hardman, J., Blair, P. H. B., Ellis, P. K., Morris, G., Odurny, A., Vohra, R., Duddy, M., Thompson, M., Loosemore, T. M. L., Belli, A. M., Morgan, R., Adiseshiah, M., Brookes, J. A. S., McCollum, C. N., Ashleigh, R., Aukett, M., Baker, S., Barbe, E., Batson, N., Bell, J., Blundell, J., Boardley, D., Boyes, S., Brown, O., Bryce, J., Carmichael, M., Chance, T., Coleman, J., Cosgrove, C., Curran, G., Dennison, T., Devine, C., Dewhirst, N., Errington, B., Farrell, H., Fisher, C., Fulford, P., Gough, M., Graham, C., Hooper, R., Horne, G., Horrocks, L., Hughes, B., Hutchings, T., Ireland, M., Judge, C., Kelly, L., Kemp, J., Kite, A., Kivela, M., Lapworth, M., Lee, C., Linekar, L., Mahmood, A., March, L., Martin, J., Matharu, N., McGuigen, K., Morris‐Vincent, P., Murray, S., Murtagh, A., Owen, G., Ramoutar, V., Rippin, C., Rowley, J., Sinclair, J., Spencer, S., Taylor, V., Tomlinson, C., Ward, S., Wealleans, V., West, J., White, K., Williams, J., Wilson, L., Grobbee, D. E., Blankensteijn, J. D., Bak, A. A. A., Buth, J., Pattynama, P. M., Verhoeven, E. L. G., van Voorthuisen, A. E., Blankensteijn, J. D., Balm, R., Buth, J., Cuypers, P. W. M., Grobbee, D. E., Prinssen, M., van Sambeek, M. R. H. M., Verhoeven, E. L. G., Baas, A. F., Hunink, M. G., van Engelshoven, J. M., Jacobs, M. J. H. M., de Mol, B. A. J. M., van Bockel, J. H., Balm, R., Reekers, J., Tielbeek, X., Verhoeven, E. L. G., Wisselink, W., Boekema, N., Heuveling, L. M., Sikking, I., Prinssen, M., Balm, R., Blankensteijn, J. D., Buth, J., Cuypers, P. W. M., van Sambeek, M. R. H. M., Verhoeven, E. L. G., de Bruin, J. L., Baas, A. F., Blankensteijn, J. D., Prinssen, M., Buth, J., Tielbeek, A.V., Blankensteijn, J. D., Balm, R., Reekers, J. A., van Sambeek, M. R. H. M., Pattynama, P., Verhoeven, E. L. G., Prins, T., van der Ham, A. C., van der Velden, J. J. I. M., van Sterkenburg, S. M. M., ten Haken, G. B., Bruijninckx, C. M. A., van Overhagen, H., Tutein Nolthenius, R. P., Hendriksz, T. R., Teijink, J. A. W., Odink, H. F., de Smet, A. A. E. A., Vroegindeweij, D., van Loenhout, R. M. M., Rutten, M. J., Hamming, J. F., Lampmann, L. E. H., Bender, M. H. M., Pasmans, H., Vahl, A. C., de Vries, C., Mackaay, A. J. C., van Dortmont, L. M. C., van der Vliet, A. J., Schultze Kool, L. J., Boomsma, J. H. B., van Dop, H. R., de Mol van Otterloo, J. C. A., de Rooij, T. P. W., Smits, T. M., Yilmaz, E. N., Wisselink, W., van den Berg, F. G., Visser, M. J. T., van der Linden, E., Schurink, G. W. H., de Haan, M., Smeets, H. J., Stabel, P., van Elst, F., Poniewierski, J., Vermassen, F. E. G., Lederle, F. A., Freischlag, J. A., Kohler, T. R., Latts, E., Matsumura, J., Padberg, F. T., Jr, Kyriakides, T. C., Swanson, K. M., Guarino, P., Peduzzi, P., Antonelli, M., Cushing, C., Davis, E., Durant, L., Joyner, S., Kossack, the late A., Kyriakides, T. C., LeGwin, Mary, McBride, V., OʼConnor, T., Poulton, J., Stratton, the late S., Zellner, S., Snodgrass, A. J., Thornton, J., Swanson, K. M., Haakenson, C. M., Stroupe, K.T., Jonk, Y., Hallett, J. W., Hertzer, N., Towne, J., Katz, D. A., Karrison, T., Matts, J. P., Marottoli, R., Kasl, S., Mehta, R., Feldman, R., Farrell, W., Allore, H., Perry, E., Niederman, J., Randall, F., Zeman, M., Beckwith, the late D., OʼLeary, T. J., Huang, G. D., Latts, E., Bader, M., Ketteler, E. R., Kingsley, D. D., Marek, J. M., Massen, R. J., Matteson, B. D., Pitcher, J. D., Langsfeld, M., Corson, J. D., Goff, J. M., Jr, Kasirajan, K., Paap, C., Robertson, D. C., Salam, A., Veeraswamy, R., Milner, R., Kasirajan, K., Guidot, J., Lal, B. K., Busuttil, S. J., Lilly, M. P., Braganza, M., Ellis, K., Patterson, M. A., Jordan, W. D., Whitley, D., Taylor, S., Passman, M., Kerns, D., Inman, C., Poirier, J., Ebaugh, J., Raffetto, J., Chew, D., Lathi, S., Owens, C., Hickson, K., Dosluoglu, H. H., Eschberger, K., Kibbe, M. R., Baraniewski, H. M., Matsumura, J., Endo, M., Busman, A., Meadows, W., Evans, M., Giglia, J. S., El Sayed, H., Reed, A. B., Ruf, M., Ross, S., Jean‐Claude, J. M., Pinault, G., Kang, P., White, N., Eiseman, M., Jones, the late R., Timaran, C. H., Modrall, J. G., Welborn, M. B., III, Lopez, J., Nguyen, T., Chacko, J. K. Y., Granke, K., Vouyouka, A. G., Olgren, E., Chand, P., Allende, B., Ranella, M., Yales, C., Whitehill, T. A., Krupski, the late W. C., Nehler, M. R., Johnson, S. P., Jones, D. N., Strecker, P., Bhola, M. A., Shortell, C. K., Gray, J. L., Lawson, J. H., McCann, R., Sebastian, M.W., Kistler Tetterton, J., Blackwell, C., Prinzo, P. A., Lee, N., Padberg, F. T., Jr, Cerveira, J. J., Lal, B. K., Zickler, R. W., Hauck, K. A., Berceli, S. A., Lee, W. A., Ozaki, C. K., Nelson, P. R., Irwin, A. S., Baum, R., Aulivola, B., Rodriguez, H., Littooy, F. N., Greisler, H., OʼSullivan, M. T., Kougias, P., Lin, P. H., Bush, R. L., Guinn, G., Bechara, C., Cagiannos, C., Pisimisis, G., Barshes, N., Pillack, S., Guillory, B., Cikrit, D., Lalka, S. G., Lemmon, G., Nachreiner, R., Rusomaroff, M., OʼBrien, E., Cullen, J. J., Hoballah, J., Sharp, W. J., McCandless, J. L., Beach, V., Minion, D., Schwarcz, T. H., Kimbrough, J., Ashe, L., Rockich, A., Warner‐Carpenter, J., Moursi, M., Eidt, J. F., Brock, S., Bianchi, C., Bishop, V., Gordon, I. L., Fujitani, R., Kubaska, S. M., III, Behdad, M., Azadegan, R., Ma Agas, C., Zalecki, K., Hoch, J. R., Carr, S. C., Acher, C., Schwarze, M., Tefera, G., Mell, M., Dunlap, B., Rieder, J., Stuart, J. M., Weiman, D. S., Abul‐Khoudoud, O., Garrett, H. E., Walsh, S. M., Wilson, K. L., Seabrook, G. R., Cambria, R. A., Brown, K. R., Lewis, B. D., Framberg, S., Kallio, C., Barke, R. A., Santilli, S. M., dʼAudiffret, A. C., Oberle, N., Proebstle, C., Johnson, L. L., Jacobowitz, G. R., Cayne, N., Rockman, C., Adelman, M., Gagne, P., Nalbandian, M., Caropolo, L. J., Pipinos, I. I., Johanning, J., Lynch, T., DeSpiegelaere, H., Purviance, G., Zhou, W., Dalman, R., Lee, J. T., Safadi, B., Coogan, S. M., Wren, S. M., Bahmani, D. D., Maples, D., Thunen, S., Golden, M. A., Mitchell, M. E., Fairman, R., Reinhardt, S., Wilson, M. A., Tzeng, E., Muluk, S., Peterson, N. M., Foster, M., Edwards, J., Moneta, G. L., Landry, G., Taylor, L., Yeager, R., Cannady, E., Treiman, G., Hatton‐Ward, S., Salabsky, the late B., Kansal, N., Owens, E., Estes, M., Forbes, B. A., Sobotta, C., Rapp, J. H., Reilly, L. M., Perez, S. L., Yan, K., Sarkar, R., Dwyer, S. S., Perez, S., Chong, K., Kohler, T. R., Hatsukami, T. S., Glickerman, D. G., Sobel, M., Burdick, T. S., Pedersen, K., Cleary, P., Back, M., Bandyk, D., Johnson, B., Shames, M., Reinhard, R. L., Thomas, S. C., Hunter, G. C., Leon, L. R., Jr, Westerband, A., Guerra, R. J., Riveros, M., Mills, J. L., Sr, Hughes, J. D., Escalante, A. M., Psalms, S. B., Day, N. N., Macsata, R., Sidawy, A., Weiswasser, J., Arora, S., Jasper, B. J., Dardik, A., Gahtan, V., Muhs, B. E., Sumpio, B. E., Gusberg, R. J., Spector, M., Pollak, J., Aruny, J., Kelly, E. L., Wong, J., Vasilas, P., Joncas, C., Gelabert, H. A., DeVirgillio, C., Rigberg, D. A., Cole, L., Becquemin, J.‐P., Marzelle, J., Becquemin, J.‐P., Sapoval, M., Becquemin, J.‐P., Favre, J.‐P., Watelet, J., Lermusiaux, P., Sapoval, M., Lepage, E., Hemery, F., Dolbeau, G., Hawajry, N., Cunin, P., Harris, P., Stockx, L., Chatellier, G., Mialhe, C., Fiessinger, J.‐N., Pagny, L., Kobeiter, H., Boissier, C., Lacroix, P., Ledru, F., Pinot, J.‐J., Deux, J.‐F., Tzvetkov, B., Duvaldestin, P., Watelet, J., Jourdain, C., David, V., Enouf, D., Ady, N., Krimi, A., Boudjema, N., Jousset, Y., Enon, B., Blin, V., Picquet, J., LʼHoste, P., Thouveny, F., Borie, H., Kowarski, S., Pernes, J.‐M., Auguste, M., Becquemin, J.‐P., Desgranges, P., Allaire, E., Marzelle, J., Kobeiter, H., Meaulle, P.‐Y., Chaix, D., Juliae, P., Fabiani, J. N., Chevalier, P., Combes, M., Seguin, A., Belhomme, D., Sapoval, M., Baque, J., Pellerin, O., Favre, J. P., Barral, X., Veyret, C., Watelet, J., Peillon, C., Plissonier, D., Thomas, P., Clavier, E., Lermusiaux, P., Martinez, R., Bleuet, F., C, Dupreix, Verhoye, J. P., Langanay, T., Heautot, J. F., Koussa, M., Haulon, S., Halna, P., Destrieux, L., Lions, C., Wiloteaux, S., Beregi, J. P., Bergeron, P., Pinot, J.‐J., Patra, P., Costargent, A., Chaillou, P., DʼAlicourt, A., Goueffic, Y., Cheysson, E., Parrot, A., Garance, P., Demon, A., Tyazi, A., Pillet, J.‐C., Lescalie, F., Tilly, G., Steinmetz, E., Favier, C., Brenot, R., Krause, D., Cercueil, J. P., Vahdat, O., Sauer, M., Soula, P., Querian, A., Garcia, O., Levade, M., Colombier, D., Cardon, J.‐M., Joyeux, A., Borrelly, P., Dogas, G., Magnan, P.‐É., Branchereau, A., Bartoli, J.‐M., Hassen‐Khodja, R., Batt, M., Planchard, P.‐F., Bouillanne, P.‐J., Haudebourg, P., Bayne, J., Gouny, P., Badra, A., Braesco, J., Nonent, M., Lucas, A., Cardon, A., Kerdiles, Y., Rolland, Y., Kassab, M., Brillu, C., Goubault, F., Tailboux, L., Darrieux, H., Briand, O., Maillard, J.‐C., Varty, K., and Cousins, C.

Published
2017
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3. Intestinal Lipid Metabolism Genes Regulated by miRNAs

Author

Ruíz-Roso, M.B. (María Belén), Gil-Zamorano, J. (Judit), Lopez-de-las-Hazas, M.C. (María-Carmen), Tomé-Carneiro, J. (Joao), Crespo, M.C. (María Carmen), Latasa, M.J. (María Jesús), Briand, O. (Olivier), Sánchez-López, D. (Daniel), Ortiz, A.I. (Ana I.), Visioli, F. (Francesco), Martinez, J.A. (José Alfredo), and Dávalos, A. (Alberto)

Subjects
Organoids, Lipid metabolism, Olr1, microRNA, Acat1, Dicer1, Small intestine, Hmgcs2
Abstract

MicroRNAs (miRNAs) crucial roles in translation repression and post-transcriptional adjustments contribute to regulate intestinal lipid metabolism. Even though their actions in different metabolic tissues have been elucidated, their intestinal activity is yet unclear. We aimed to investigate intestinal miRNA-regulated lipid metabolism-related genes, by creating an intestinal-specific Dicer1 knockout (Int-Dicer1 KO) mouse model, with a depletion of microRNAs in enterocytes. The levels of 83 cholesterol and lipoprotein metabolism-related genes were assessed in the intestinal mucosa of Int-Dicer1 KO and Wild Type C57BL/6 (WT) littermates mice at baseline and 2 h after an oral lipid challenge. Among the 18 genes selected for further validation, Hmgcs2, Acat1 and Olr1 were found to be strong candidates to be modulated by miRNAs in enterocytes and intestinal organoids. Moreover, we report that intestinal miRNAs contribute to the regulation of intestinal epithelial differentiation. Twenty-nine common miRNAs found in the intestines were analyzed for their potential to target any of the three candidate genes found and validated by miRNA-transfection assays in Caco-2 cells. MiR-31-5p, miR99b-5p, miR-200a-5p, miR-200b-5p and miR-425-5p are major regulators of these lipid metabolism-related genes. Our data provide new evidence on the potential of intestinal miRNAs as therapeutic targets in lipid metabolism-associated pathologies.

Published
2020

4. Endospanin-2 enhances skeletal muscle energy metabolism and running endurance capacity

Author

Lancel, S. (Steve), Hesselink, M.K. (Matthijs Kc), Woldt, E. (Estelle), Rouille, Y. (Yves), Dorchies, E. (Emilie), Delhaye, S. (Stephane), Duhem, C. (Christian), Thorel, Q. (Quentin), Mayeuf-Louchart, A. (Alicia), Pourcet, B. (Benoit), Montel, V. (Valerie), Schaart, G. (Gert), Beton, N. (Nicolas), Picquet, F. (Florence), Briand, O. (Olivier), Salles, J.P. (Jean Pierre), Duez, H. (Helene), Schrauwen, P. (Patrick), Bastide, B. (Bruno), Bailleul, B. (Bernard), Staels, B. (Bart), Sebti, Y. (Yasmine), Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM), Maastricht University [Maastricht], Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Unité de Recherche Pluridisciplinaire Sport, Santé, Société (URePSSS) - ULR 7369 - ULR 4488 (URePSSS), Université d'Artois (UA)-Université de Lille-Université du Littoral Côte d'Opale (ULCO), Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), European Project: 694717,H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) ,ImmunoBile(2016), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Université d'Artois (UA)-Université du Littoral Côte d'Opale (ULCO)-Université de Lille, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Récepteurs nucléaires, maladies cardiovasculaires et diabète (EGID), 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-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Maastricht University Medical Center (MUMC), Centre d’Infection et d’Immunité de Lille (CIIL) - INSERM U1019 - UMR 9017 (CIIL), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Unité de Recherche Pluridisciplinaire Sport, Santé, Société (URePSSS) - EA 7369 (URePSSS), Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Université d'Artois (UA), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP), This research was supported by the European Genomic Institute for Diabetes (EGID, ANR-10-LABX-46) and European Commission, Lille Métropole Communauté Urbaine (to YS), Région Nord Pas-de-Calais/FEDER (to BS), CPER 2011-R3-P12A (to B. Bailleul), a joint Société Francophone du Diabète (SFD)/Menarini research fellowship (to B. Bailleul), EFSD/Lilly research grant and CPER emerging team (to HD), Eurhythdia (to BS and HD), ERC Région Haut de France (to HD), and Pfizer France and Ipsen Beaufour (to JPS). BS hold an ERC advanced grant (no. 694717)., ANR-10-LABX-0046/10-LABX-0046,EGID,EGID Diabetes Pole(2010), Nutrition and Movement Sciences, RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, Ondersteunend personeel NTM, Université de Lille, Univ. Artois, Univ. Littoral Côte d’Opale, Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 [RNMCD], Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 [CIIL], Unité de Recherche Pluridisciplinaire Sport, Santé, Société (URePSSS) - ULR 7369 - ULR 4488 [URePSSS], and Centre de Physiopathologie Toulouse Purpan [CPTP]

Subjects
Male, [SDV]Life Sciences [q-bio], Cell Plasticity, Messenger, Skeletal muscle, [SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC], MOUSE, STAT3, Mice, Phosphorylation, Extracellular Signal-Regulated MAP Kinases, Cells, Cultured, Glucose metabolism, Cultured, ACTIVATED PROTEIN-KINASE, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, MITOCHONDRIAL BIOGENESIS, Skeletal, Mitochondria, ERK, Muscle Fibers, Slow-Twitch, Phenotype, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Muscle Fibers, Fast-Twitch, Muscle, Female, PHENOTYPIC ANALYSIS, Research Article, PERMEABILITY TRANSITION, MAP Kinase Signaling System, Cells, Physical Exertion, EXERCISE, Slow-Twitch, Muscle Fibers, Signal Transducing, Animals, Autophagy, Caloric Restriction, Energy Metabolism, Humans, Membrane Proteins, Fast-Twitch, Oxidative Stress, Physical Endurance, RNA, Metabolism, Muscle Biology, RNA, Messenger, Muscle, Skeletal, Adaptor Proteins, Signal Transducing, ELECTRON-TRANSPORT CHAIN
Abstract

International audience; Metabolic stresses such as dietary energy restriction or physical activity exert beneficial metabolic effects. In the liver, endospanin-1 and endospanin-2 cooperatively modulate calorie restriction-mediated (CR-mediated) liver adaptations by controlling growth hormone sensitivity. Since we found CR to induce endospanin protein expression in skeletal muscle, we investigated their role in this tissue. In vivo and in vitro endospanin-2 triggers ERK phosphorylation in skeletal muscle through an autophagy-dependent pathway. Furthermore, endospanin-2, but not endospanin-1, overexpression decreases muscle mitochondrial ROS production, induces fast-to-slow fiber-type switch, increases skeletal muscle glycogen content, and improves glucose homeostasis, ultimately promoting running endurance capacity. In line, endospanin-2-/- mice display higher lipid peroxidation levels, increased mitochondrial ROS production under mitochondrial stress, decreased ERK phosphorylation, and reduced endurance capacity. In conclusion, our results identify endospanin-2 as a potentially novel player in skeletal muscle metabolism, plasticity, and function.

Published
2018

5. Transferts de pesticides et réduction de la contamination de l'environnement : part. 1

Author

Alencastro, L.P., Andrieux, Patrick, Bedos, Carole, Benoit, P., Briand, O., Brunet, Yves, Carluer, Nadia, Cattan, P., Chevreuil, Marc, Coquet, Yves, Delmas, François, Gouy, Véronique, Mellouki, W., Real, B., Vernier, Françoise, Charbonnier, Edwige, Ronceux, Aïcha, Carpentier, A.S., Soubelet, Hélène, Barriuso, E., ECOLE POLYTECHNIQUE FEDERALE LAUSANNE CH, Partenaires IRSTEA, Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Institut National de la Recherche Agronomique (INRA), Ecologie fonctionnelle et écotoxicologie des agroécosystèmes (ECOSYS), Institut National de la Recherche Agronomique (INRA)-AgroParisTech, MAAF PARIS FRA, Milieux aquatiques, écologie et pollutions (UR MALY), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad), Milieux Environnementaux, Transferts et Interactions dans les hydrosystèmes et les Sols (METIS), École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Université d'Orléans (UO), Ecosystèmes aquatiques et changements globaux (UR EABX), Centre National de la Recherche Scientifique (CNRS), ARVALIS - Institut du végétal [Paris], MEDDE PARIS FRA, and Irstea Publications, Migration

Subjects
[SDE] Environmental Sciences, [SDE]Environmental Sciences, FRANCE
Abstract

National audience; Quatre projets pionniers en France existent sur la dynamique des pesticides dans l'atmosphère. Ils se sont intéressés au passage en milieu aérien, pendant et après l'application, et au devenir des pesticides dans l'atmosphère. Le chapitre 1 leur est consacré. Cinq projets ont traité du transfert et du devenir des pesticides dans les sols et les eaux continentales - superficielles ou souterraines-, dans différents bassins versants agricoles de France métropolitaine ; leurs résultats sont présentés dans le chapitre 2.

Published
2015

7. Guide : développement d'un outil d'aide à la sélection d'indicateurs de risques liés à la présence des produits phytopharmaceutiques dans les milieux aquatiques : Mise au point, applications et perspectives

Author

Keichinger, O., Benoit, P., Boivin, A., Bourrain, X., Briand, O., Chabert, A., Domange, N., Dubus, I., Gouy, V., Guichard, L., Pitrel, M., Pleyber, E., Roulier, S., Zahm, F., Bockstaller, C., Agronomie, Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Laboratoire de sécurité des aliments de Maisons-Alfort, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Agence de l'Eau Loire Bretagne, MAAPRAT, ACTA, Institut Claude Bourgelat (ICLB), Office national de l'eau et des milieux aquatiques (ONEMA), Ministère de l'écologie, du développement durable et de l'énergie, Footways, Milieux aquatiques, écologie et pollutions (UR MALY), Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Agence de l'Eau Rhin-Meuse, DGALN, MEDDE, Aménités et dynamiques des espaces ruraux (UR ADBX), Laboratoire Agronomie et Environnement (LAE), Institut National de la Recherche Agronomique (INRA)-Université de Lorraine (UL), and AgroParisTech-Institut National de la Recherche Agronomique (INRA)

Subjects
RISK, PESTICIDE, [SDE]Environmental Sciences, QUALITE DE L'EAU, WATER QUALITY, INDICATEUR DE POLLUTION, AIDE A LA DECISION, INDICATOR, EVALUATION DES RISQUES
Abstract

Dans le domaine de l’évaluation des risques liés à la présence des produits phytopharmaceutiques dans les milieux aquatiques comme pour d’autres problématiques environnementales, de très nombreux indicateurs ont été développés depuis une vingtaine d’années. Pour aider les utilisateurs à choisir l’indicateur le plus approprié à leur questionnement, le projet GUIDE a développé un outil disponible sur internet comprenant des fiches descriptives des indicateurs disponibles mettant à jour l’ouvrage de Devillers et al. (2005) mais aussi et surtout une aide au choix interactive. Deux applications dans le cadre du plan Ecophyto 2018 sont issues de ce travail : l’une porte sur le choix d’indicateurs de risque vis-à-vis de la qualité de l’eau à intégrer dans l’outil Coclick’eau pour soutenir la construction des plans d'action sur les aires d’alimentation des captages (action 21) ; l’autre porte sur le choix d’indicateurs à utiliser au niveau national pour déterminer l’évolution des risques pour la qualité de l’eau liée à l’évolution de l'utilisation des produits phytopharmaceutiques. / A great number of indicators were developed for the last twenty years, to assess the risk of pesticide use, like for other environmental issues. The GUIDE project aimed at developing a web site to help the potential users to select an indicators meeting their needs. The tool updating the book of Devillers et al. (2005) and available on internet, consists of factsheets describing the indicators, and especially of an interactive tool to help users in selecting an indicator. Two applications in the context of the Ecophyto 2018 plan came out from this work: the first example concerns the selection of risk indicators addressing water quality that have to be integrated into the Coclick'eau tool to support the construction of action plan for catchment area (action 21). In the second example, indicators were proposed to provide information at national level on the pesticide risk linked to the reduction of pesticide use.

Published
2013

8. GUIDE : développement d'un outil d'aide à la sélection d'indicateurs de risques liés à la présence des produits phytopharmaceutiques dans les milieux aquatiques - Mise au point, applications et perspectives

Author

Keichinger , O., Benoit, Pierre, Boivin , A., Bourrain , X., Briand , O., Chabert , A., Domange , N., Dubus, I., Gouy, V., Guichard, Laurence, Pitrel, M., Pleyber, E., Roulier S. , Zahm F., and Bockstaller, Christian

Subjects
indicateur, risque, produit phytopharmaceutique, transfert, qualité de l’eau, qualité de l'eau, milieu aquatique
Abstract

Dans le domaine de l’évaluation des risques liés à la présence des produits phytopharmaceutiques dans les milieux aquatiques comme pour d’autres problématiques environnementales, de très nombreux indicateurs ont été développés depuis une vingtaine d’années. Pour aider les utilisateurs à choisir l’indicateur le plus approprié à leur questionnement, le projet GUIDE a développé un outil disponible sur internet comprenant des fiches descriptives des indicateurs disponibles, mettant à jour l’ouvrage de Devillers et al. (2005) mais constituant aussi et surtout une aide au choix interactive. Deux applications dans le cadre du plan Ecophyto 2018 sont issues de ce travail : l’une porte sur le choix d’indicateurs de risque vis-à-vis de la qualité de l’eau à intégrer dans l’outil Coclick’eau pour soutenir la construction des plans d'action sur les aires d’alimentation des captages (Action 21); l’autre porte sur le choix d’indicateurs à utiliser au niveau national pour déterminer l’évolution des risques pour la qualité de l’eau liée à l’évolution de l'utilisation des produits phytopharmaceutiques., A great number of indicators have been developed during the last twenty years for many environmental issues, including for the assessment of the risk associated with pesticide use. The GUIDE project aimed at developing a web site to help potential users to select indicators meeting their needs. The tool updating the book of Devillers et al. (2005) and available on internet, comprises a set of factsheets describing the various indicators, and an interface to help users in selecting an indicator. Two applications in the context of the Ecophyto 2018 national plan have been performed: the first example concerns the selection of risk indicators addressing water quality that have to be integrated into the Coclick'eau tool to support the construction of action plan for catchment area (Action 21). In the second example, indicators were proposed to provide information on the change in pesticide risk for water quality linked to the reduction of pesticide use.

Published
2013

9. Gestion alternative des eaux pluviales en aménagement urbain

Author

Briand, O., Gautier, M.L., Hélou, F., Geffroy, F., Ricard, B., SAFEGE, and Brelot, Elodie

Subjects
Stratégie, [SDE.IE]Environmental Sciences/Environmental Engineering, Strategy
Abstract

Colloque avec actes et comité de lecture. Internationale.; International audience

Published
2010

11. Chikunggunya et autres arboviroses en milieu tropical

Author

Rolland, M., Corbel, Vincent, Darriet, Frédéric, Marcombe, Sébastien, Briand, O., Yamada, O., Rousselle, C., Bavoux, C., Fastier, A., Mandin, C., Serre, P., Thybaud, E., and Ambroise Thomas, P. (dir.)

Subjects
BIT, DELTAMETHRINE, VECTEUR, EVALUATION, INSECTICIDE CHIMIQUE, EPIDEMIE, METHODE DE LUTTE, PYRETHRE, ETUDE COMPARATIVE, NALED, GESTION DU RISQUE, MOUSTIQUE, ARBOVIROSE, EFFICACITE, PYRIPROXYLENE
Published
2007

12. Chikunggunya et autres arboviroses en milieu tropical

Author

Carnevale, Pierre, Darriet, Frédéric, Delaunay, P.L., Deparis, X., Hubert, F., Jaeg, J.P., Legros, Fabrice, Pages, F., Robert, Vincent, Rousselle, C., Briand, O., and Ambroise Thomas, P. (dir.)

Subjects
EPIDEMIOLOGIE, DELTAMETHRINE, RECOMMANDATION, VECTEUR, PREVENTION SANITAIRE, VETEMENT IMPREGNE, PERMETHRINE, EVALUATION, INSECTICIDE CHIMIQUE, METHODE DE LUTTE, GESTION DU RISQUE, MOUSTIQUE, ARBOVIROSE, MOUSTIQUAIRE IMPREGNEE
Published
2007

13. Passive samplers as a key tool to estimate exposure to pesticides on different time scale

Author

Tuduri, L., Guillet, V., Montury, M., Millet, M., Briand, O., Aunis, Danièle, Centre de géochimie de la surface (CGS), Centre National de la Recherche Scientifique (CNRS)-Université Louis Pasteur - Strasbourg I-Institut national des sciences de l'Univers (INSU - CNRS), and Institut national des sciences de l'Univers (INSU - CNRS)-Université Louis Pasteur - Strasbourg I-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDU.OCEAN]Sciences of the Universe [physics]/Ocean, Atmosphere, [SDU.OCEAN] Sciences of the Universe [physics]/Ocean, Atmosphere, [SDE.MCG.CPE]Environmental Sciences/Global Changes/domain_sde.mcg.cpe, [SDE.MCG.CPE] Environmental Sciences/Global Changes/domain_sde.mcg.cpe
Published
2007

15. PO32 L’activation du récepteur nucléaire FXR module la capacité des cellules L entéroendocrines à sécréter GLP-1

Author

Trabelsi, M., primary, Daoudi, M., additional, Touche, V., additional, Briand, O., additional, Dehondt, H., additional, Prawitt, J., additional, Dorchies, E., additional, Hennuyer, N., additional, Caron-Houde, S., additional, Baud, G., additional, Caiazzo, R., additional, Tailleux, A., additional, Pattou, F., additional, Staels, B., additional, and Lestavel, S., additional

Published
2014
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16. Atmospheric contamination by pesticides: a review on French studies

Author

Millet, M., Bedos, Carole, Briand, O., Cellier, Pierre, Barriuso, Enrique, Mirabel, P., Seux, R., Unité de recherches en bioclimatologie, Institut National de la Recherche Agronomique (INRA), and ProdInra, Migration

Subjects
[SDV] Life Sciences [q-bio], [SDE] Environmental Sciences, [SDV]Life Sciences [q-bio], [SDE]Environmental Sciences, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2001

17. Field experiment to assess pesticide post-application transfers to the atmosphere. About determining volatilization fluxes

Author

Briand, O., Bertrand, F., Millet, M., Seux, R., ECOLE NATIONALE DE LA SANTE PUBLIQUE RENNES, Partenaires IRSTEA, Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Laboratoire d'Hydrologie et de Géochimie de Strasbourg (LHyGeS), École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Université de Strasbourg (UNISTRA)-Institut national des sciences de l'Univers (INSU - CNRS)-Ecole et Observatoire des Sciences de la Terre (EOST), Institut national des sciences de l'Univers (INSU - CNRS)-Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Ecole et Observatoire des Sciences de la Terre (EOST), Université de Strasbourg (UNISTRA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École Nationale du Génie de l'Eau et de l'Environnement de Strasbourg (ENGEES)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), and Irstea Publications, Migration

Subjects
[SDE] Environmental Sciences, [SDE]Environmental Sciences
Abstract

The consideration of pesticides in atmosphere is recent in France. And it doesn't exist surveillance program of atmospheric contamination by pesticide products as it exists for other industrial pollutants (ozone, NOx...). Indeed it is not of quantifying an unique pollutant but more than 500 different active materials in about 7000 commercial formulations. It is imaginary to believe that the next years will see being born an universal method allowing to measure all the susceptible pesticides to be present in the atmosphere. We turn more credibly to the development of mathematical models for the estimation of fluxes transfers of pesticides towards the air compartment from the treated surfaces. These last ones coupled with distribution and deposit models will allow to estimate contamination levels according to removal from sources. Three different phenomena are at the origin of the presence of pesticides in the air. The departures in the atmosphere are made from treatments (spray-drift); then by eolian erosion from treated grounds (contaminated dusts) and by more complex phenomena (transfers under gas phase and co-distillation). The development of mathematical models of transfers of pesticides since the treated surfaces passes by understanding the phenomena of transfers and the identification of the factors which control them. The nature of the ground, the climatic conditions during the application and the physico-chemical properties of compounds are so many factors which influence mechanisms and importance of these departures towards the atmosphere. LERES developed a technique of trapping and analysis of some compound presents in the air. It is based on a trapping of compounds on a resin, then a thermal desorption before analyze by GC/MS. This technique, which allows to treat quickly a great number of samples, allowed us to determine a vertical gradient of concentrations of two herbicides, atrazine and alachlore, applied on maize, during 4 days following the treatment. Coupled with micrometeorological measures, these data allow to determine fluxes of transfers., Une technique de prélèvement et d'analyse a été développée au LERES pour suivre les départs d'atrazine et d'alachlore depuis une parcelle de maïs traitée. Un gradient de concentrations en phytosanitaires a été déterminé de manière à pouvoir calculer des flux de transferts à partir des données micrométéorologiques. Nous avons pu observer l'existence de cycles de départs diurnes-nocturnes très marqués pour les deux composés. Cependant, il faut noter de forts écarts entre les départs d'atrazine et d'alachlore qui sont à mettre en relation avec les propriétés physico-chimiques de ces deux molécules et leur dose d'application. La comparaison des profils d'évolution spatio-temporelle des concentrations et des flux illustre l'intérêt des flux pour l'interprétation des mécanismes de départ de post-application et l'identification des facteurs contrôlant ces processus.

Published
2001

18. Thin film transistors fabricated by in-situ doped unhydrogenated polysilicon films obtained by solid phase crystallization

Author

Pichon, Laurent, Mourgues F. Raoult T. Mohammed-Brahim K. Kis-Sion D. Briand O. Bonnaud, K., Pichon, Laurent, Groupe de Microélectronique et Visualisation, and Université de Rennes (UR)

Subjects
[SPI.NANO] Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics, [SPI.NANO]Engineering Sciences [physics]/Micro and nanotechnologies/Microelectronics
Abstract

International audience; High mobility low temperature (≤ 600°C) unhydrogenated in-situ doped polysilicon thin film transistors are made. Polysilicon layers are grown by a LPCVD technique and crystallized in vacuum by a thermal annealing. Source and drain regions are in-situ doped. Gate insulator is made of an APCVD silicon dioxide. Hydrogen passivation is not performed on the transistors. One type of transistors is made of two polysilicon layers, the other one is constituted of a single polysilicon layer. The electrical properties are better for transistors made of single polysilicon layer: a low threshold voltage (1.2 V), a subthreshold slope S = 0.7 V/dec, a high field effect mobility (≈ 100 cm2/Vs) and a On/Off state current ratio higher than 107 for a drain voltage Vds = 1 V. At low drain voltage, for both transistors, the Off state current results from a pure thermal emission of trapped carriers. However, at high drain voltage, the electrical behavior is different: in the case of single polysilicon TFTs, the current obeys the field-assisted (Poole-Frenkel) thermal emission model of trapped carriers while for TFTs made of two polysilicon layers, the higher Off state current results from a field-enhanced thermal emission.

Published
2001

21. Quels outils d’estimation des expositions aux produits phytopharmaceutiques utiliser pour assurer une traçabilité des expositions sur le long terme : exemple des agents des collectivités territoriales ?

Author

Teigné, D., primary, Dulaurent, S., additional, Deygout, F., additional, Delhomme, O., additional, Raeppel, C., additional, Tuduri, L., additional, Moesch, C., additional, Millet, M., additional, Briand, O., additional, Lévy, M.-P., additional, and Auburtin, G., additional

Published
2012
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23. Applicabilité d’outils d’estimation des expositions aux produits phytopharmaceutiques en vue d’une surveillance professionnelle sur le long terme : exemple des agents des collectivités territoriales

Author

Teigné, D., primary, Dulaurent, S., additional, Deygout, F., additional, Delhomme, O., additional, Raeppel, C., additional, Tuduri, L., additional, Moesch, C., additional, Millet, M., additional, Briand, O., additional, Levy, M.-P., additional, and Auburtin, G., additional

Published
2012
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25. O37 Le récepteur nucléaire FXR régule la fonction et la différenciation adipocytaire en interférant avec la voie Wnt/β-caténine et en induisant la voie de signalisation de PPARγ

Author

Abdelkarim, M., primary, Caron, S., additional, Duhem, C., additional, Prawitt, J., additional, Dumont, J., additional, Bouchaert, E., additional, Briand, O., additional, Brozek, J., additional, Kuipers, F., additional, Fievet, C., additional, Cariou, B., additional, and Staels, B., additional

Published
2010
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31. Performance study of multi-rate output controllers under noise disturbances

Author

ER, MENGJ. and ANDERSON, BRIAND. O.

Abstract

This paper presents a comparative study of the performance of a multi-rate output controller (MROC) with a linear quadratic gaussian (LQG) controller in the presence of noise disturbances and anti-aliasing filters. The basis of comparison is to apply an LQG law with a one-step-ahead prediction-type Kalman filter (hereafter called LQG law I) and an LQG law with a current estimation-type Kalman filter (hereafter called LQG law II) to a linear time-invariant continuous-time plant model with a white gaussian process and measurement noise and compute a linear quadratic performance index for the discretized plant. Equivalent noise matrices for using the MROC law are derived and the same quadratic performance index computed. In order to have a fair comparison, the cut-off frequency of the anti-aliasing filter used to remove high frequency noise components prior to sampling is also kept the same when applying both laws. Application of both laws in typical situations shows that the performance of the MROC law is worse than either that of LQG law I or LQG law II.

Published
1992
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33. GUIDE : développement d'un outil d'aide à la sélection d'indicateurs de risques liés à la présence des produits phytopharmaceutiques dans les milieux aquatiques - Mise au point, applications et perspectives

Author

Keichinger, O., Pierre Benoit, Boivin, A., Bourrain, X., Briand, O., Chabert, A., Domange, N., Dubus, I., Gouy, V., Laurence Guichard, Pitrel, M., Pleyber, E., Frédéric Zahm, Christian Bockstaller, ProdInra, Migration, Environnement et Grandes Cultures (EGC), AgroParisTech-Institut National de la Recherche Agronomique (INRA), Institut Claude Bourgelat (ICLB), Direction de l'Action Scientifique et Technique, Office National de l'eau et des milieux aquatiques, Unité MAEP, Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), Agronomie, Aménités et dynamiques des espaces ruraux (UR ADBX), Laboratoire Agronomie et Environnement - Antenne Colmar (LAE-Colmar ), Laboratoire Agronomie et Environnement (LAE), Institut National de la Recherche Agronomique (INRA)-Université de Lorraine (UL)-Institut National de la Recherche Agronomique (INRA)-Université de Lorraine (UL), Independent, Institut National de la Recherche Agronomique (INRA)-AgroParisTech, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Agence de l'Eau Loire-Bretagne, Ministère de l'Agriculture, de l'Alimentation, de la Pêche, de la ruralité et de l'Aménagement du territoire (MAAPRAT), Association de Coordination Technique Agricole (ACTA), Footways, Agence de l'Eau Rhin-Meuse, MEDDE - DGALN - DEB, and Partenaires INRAE

Subjects
[SDV.SA]Life Sciences [q-bio]/Agricultural sciences, [SDV] Life Sciences [q-bio], [SDE] Environmental Sciences, transfert, produit phytopharmaceutique, risque, [SDV]Life Sciences [q-bio], [SDE]Environmental Sciences, qualité de l'eau, indicateur, ComputingMilieux_MISCELLANEOUS
Abstract

Séminaire organisé en janvier 2013 par le groupe Recherche Ecophyto; Dans le domaine de l'évaluation des risques liés à la présence des produits phytopharmaceutiques dans les milieux aquatiques comme pour d'autres problématiques environnementales, de très nombreux indicateurs ont été développés depuis une vingtaine d'années. Pour aider les utilisateurs à choisir l'indicateur le plus approprié à leur questionnement, le projet GUIDE a développé un outil disponible sur internet comprenant des fiches descriptives des indicateurs disponibles, mettant à jour l'ouvrage de Devillers et al. (2005) mais constituant aussi et surtout une aide au choix interactive. Deux applications dans le cadre du plan Ecophyto 2018 sont issues de ce travail : l'une porte sur le choix d'indicateurs de risque vis-à-vis de la qualité de l'eau à intégrer dans l'outil Coclick'eau pour soutenir la construction des plans d'action sur les aires d'alimentation des captages (Action 21); l'autre porte sur le choix d'indicateurs à utiliser au niveau national pour déterminer l'évolution des risques pour la qualité de l'eau liée à l'évolution de l'utilisation des produits phytopharmaceutiques.

35. La lutte antivectorielle dans le cadre de l'épidémie de chikungunya sur l'île de la Réunion : évaluation des risques liés à l'utilisation des produits insecticides d'imprégnation des moustiquaires et des vêtements : avis de l'Afsset, synthèse bibliographique de l'Institut de recherche pour le développement, rapport du groupe de travail

Author

Briand, O. (coord.), Rousselle, C. (coord.), Carnevale, Pierre (collab.), Darriet, Frédéric (collab.), Hubert, F. (collab.), Delaunay, P. (collab.), Deparis, X. (collab.), Jaeg, J.P. (collab.), Legros, Fabrice (collab.), Pages, F. (collab.), Robert, Vincent (collab.), and Collet, R. (collab.)

Subjects
EPIDEMIOLOGIE, DELTAMETHRINE, TOXICITE, PYRETHROIDES, PHARMACOCINETIQUE, RECOMMANDATION, VECTEUR, VETEMENT IMPREGNE, PERMETHRINE, ENFANT, EVALUATION, TOXICOLOGIE, INSECTICIDE CHIMIQUE, METHODE DE LUTTE, ETUDE COMPARATIVE, MOUSTIQUE, DYNAMIQUE DE POPULATION, ARBOVIROSE, ADULTE, EFFICACITE, MOUSTIQUAIRE IMPREGNEE, ECOLOGIE
Published
2007

36. Oral metformin transiently lowers post-prandial glucose response by reducing the apical expression of sodium-glucose co-transporter 1 in enterocytes.

Author

Zubiaga L, Briand O, Auger F, Touche V, Hubert T, Thevenet J, Marciniak C, Quenon A, Bonner C, Peschard S, Raverdy V, Daoudi M, Kerr-Conte J, Pasquetti G, Koepsell H, Zdzieblo D, Mühlemann M, Thorens B, Delzenne ND, Bindels LB, Deprez B, Vantyghem MC, Laferrère B, Staels B, Huglo D, Lestavel S, and Pattou F

Abstract

Metformin (MET) is the most prescribed antidiabetic drug, but its mechanisms of action remain elusive. Recent data point to the gut as MET's primary target. Here, we explored the effect of MET on the gut glucose transport machinery. Using human enterocytes (Caco-2/TC7 cells) in vitro , we showed that MET transiently reduced the apical density of sodium-glucose transporter 1 (SGLT1) and decreased the absorption of glucose, without changes in the mRNA levels of the transporter. Administered 1 h before a glucose challenge in rats (Wistar, GK), C57BL6 mice and mice pigs, oral MET reduced the post-prandial glucose response (PGR). This effect was abrogated in SGLT1-KO mice. MET also reduced the luminal clearance of 2-( 18 F)-fluoro-2-deoxy-D-glucose after oral administration in rats. In conclusion, oral metformin transiently lowers post-prandial glucose response by reducing the apical expression of SGLT1 in enterocytes, which may contribute to the clinical effects of the drug., Competing Interests: The authors declare no competing interests., (© 2023.)

Published
2023
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37. An Exploratory Study of the Role of Dietary Proteins in the Regulation of Intestinal Glucose Absorption.

Author

Dugardin C, Fleury L, Touche V, Ahdach F, Lesage J, Tenenbaum M, Everaert N, Briand O, Lestavel S, Ravallec R, and Cudennec B

Abstract

Several studies have demonstrated that high protein diets improve glucose homeostasis. Nevertheless, the mechanisms underlying this effect remain elusive. This exploratory study aims to screen and compare the acute effects of dietary proteins from different sources on intestinal glucose absorption. Six dietary proteins from various sources were thus selected and digested thanks to the INFOGEST static gastrointestinal digestion protocol. The digested proteins were able to decrease intestinal glucose absorption in vitro and ex vivo . Moreover, acute ingestion of casein and fish gelatin led to improved glucose tolerance in Wistar rats without significant effect on insulin secretion. In parallel, GLUT2 mRNA expression in enterocytes was decreased following short-term incubation with some of the digested proteins. These results strengthen the evidence that digested protein-derived peptides and amino acids are key regulators of glucose homeostasis and highlight their role in intestinal glucose absorption., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Dugardin, Fleury, Touche, Ahdach, Lesage, Tenenbaum, Everaert, Briand, Lestavel, Ravallec and Cudennec.)

Published
2022
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38. Hair versus urine for the biomonitoring of pesticide exposure: Results from a pilot cohort study on pregnant women.

Author

Hardy EM, Dereumeaux C, Guldner L, Briand O, Vandentorren S, Oleko A, Zaros C, and Appenzeller BMR

Subjects
Biological Monitoring, Cohort Studies, Environmental Exposure analysis, Environmental Monitoring, Female, Humans, Pilot Projects, Pregnancy, Pregnant Women, Tandem Mass Spectrometry, Environmental Pollutants analysis, Pesticides analysis
Abstract

Background/aim: The quantitative assessment of human exposure to contaminants such as pesticides is a crucial step in the characterization of exposure-associated risk. For this purpose, biomonitoring is often privileged as it presents the advantage of integrating all the possible sources and routes of exposure and of being representative of the internal dose resulting from exposure. Although biological fluids such as urine and blood have been used to date for this purpose, increasing interest has also been observed over the past decade for hair analysis. The present work aimed at comparing the information obtained from the analysis of urine versus hair regarding exposure to pesticides in a pilot cohort of pregnant women., Methods: In ninety-three pregnant women included in the pilot of the French cohort ELFE, one urine and one hair sample were collected simultaneously from each subject at the maternity. Samples were analyzed using GC-MS/MS analytical methods allowing for the detection of both parent pesticides and metabolites, and designed to be as similar as possible between urine and hair for reliable inter-matrix comparison. Fifty-two biomarkers of exposure were targeted, including parents and metabolites of organochlorines, organophosphates, pyrethroids, carbamates, phenylpyrazoles and other pesticides., Results: The number of different compounds detected ranged from 16 to 27 (median = 22) in hair, and from 3 to 22 (median = 12) in urine. In hair, 24 compounds were found in > 40% of the individuals, whereas only 12 compounds presented the same frequency of detection in urine. Among the chemicals detected in > 80% of both hair and urine samples, only one (pentachlorophenol) showed a signification correlation between hair and urine concentrations., Conclusions: The present results highlight the multiple exposure of the pregnant women included in this cohort and suggest that hair provides more comprehensive information on pesticide exposure than urine analysis. This study thus supports the relevance of hair analysis in future epidemiological studies investigating association between exposure and adverse health effects., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Published
2021
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39. Intestinal miRNAs regulated in response to dietary lipids.

Author

Gil-Zamorano J, Tomé-Carneiro J, Lopez de Las Hazas MC, Del Pozo-Acebo L, Crespo MC, Gómez-Coronado D, Chapado LA, Herrera E, Latasa MJ, Ruiz-Roso MB, Castro-Camarero M, Briand O, and Dávalos A

Subjects
Adult Stem Cells chemistry, Adult Stem Cells cytology, Adult Stem Cells drug effects, Animals, Caco-2 Cells, Cell Differentiation drug effects, Cells, Cultured, DEAD-box RNA Helicases genetics, Female, Gene Deletion, Gene Expression Profiling, Gene Expression Regulation drug effects, Humans, Intestines chemistry, Intestines cytology, Lipid Metabolism, Male, Mice, Organoids chemistry, Organoids cytology, Ribonuclease III genetics, Sequence Analysis, RNA, Sex Characteristics, Time Factors, Dietary Fats pharmacology, Intestines drug effects, MicroRNAs genetics, Organoids drug effects
Abstract

The role of miRNAs in intestinal lipid metabolism is poorly described. The small intestine is constantly exposed to high amounts of dietary lipids, and it is under conditions of stress that the functions of miRNAs become especially pronounced. Approaches consisting in either a chronic exposure to cholesterol and triglyceride rich diets (for several days or weeks) or an acute lipid challenge were employed in the search for intestinal miRNAs with a potential role in lipid metabolism regulation. According to our results, changes in miRNA expression in response to fat ingestion are dependent on factors such as time upon exposure, gender and small intestine section. Classic and recent intestinal in vitro models (i.e. differentiated Caco-2 cells and murine organoids) partially mirror miRNA modulation in response to lipid challenges in vivo. Moreover, intestinal miRNAs might play a role in triglyceride absorption and produce changes in lipid accumulation in intestinal tissues as seen in a generated intestinal Dicer1-deletion murine model. Overall, despite some variability between the different experimental cohorts and in vitro models, results show that some miRNAs analysed here are modulated in response to dietary lipids, hence likely to participate in the regulation of lipid metabolism, and call for further research.

Published
2020
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40. Intestinal Lipid Metabolism Genes Regulated by miRNAs.

Author

Ruiz-Roso MB, Gil-Zamorano J, López de Las Hazas MC, Tomé-Carneiro J, Crespo MC, Latasa MJ, Briand O, Sánchez-López D, Ortiz AI, Visioli F, Martínez JA, and Dávalos A

Abstract

MicroRNAs (miRNAs) crucial roles in translation repression and post-transcriptional adjustments contribute to regulate intestinal lipid metabolism. Even though their actions in different metabolic tissues have been elucidated, their intestinal activity is yet unclear. We aimed to investigate intestinal miRNA-regulated lipid metabolism-related genes, by creating an intestinal-specific Dicer1 knockout (Int-Dicer1 KO) mouse model, with a depletion of microRNAs in enterocytes. The levels of 83 cholesterol and lipoprotein metabolism-related genes were assessed in the intestinal mucosa of Int-Dicer1 KO and Wild Type C57BL/6 (WT) littermates mice at baseline and 2 h after an oral lipid challenge. Among the 18 genes selected for further validation, Hmgcs2 , Acat1 and Olr1 were found to be strong candidates to be modulated by miRNAs in enterocytes and intestinal organoids. Moreover, we report that intestinal miRNAs contribute to the regulation of intestinal epithelial differentiation. Twenty-nine common miRNAs found in the intestines were analyzed for their potential to target any of the three candidate genes found and validated by miRNA-transfection assays in Caco-2 cells. MiR-31-5p, miR-99b-5p, miR-200a-5p, miR-200b-5p and miR-425-5p are major regulators of these lipid metabolism-related genes. Our data provide new evidence on the potential of intestinal miRNAs as therapeutic targets in lipid metabolism-associated pathologies., (Copyright © 2020 Ruiz-Roso, Gil-Zamorano, López de las Hazas, Tomé-Carneiro, Crespo, Latasa, Briand, Sánchez-López, Ortiz, Visioli, Martínez and Dávalos.)

Published
2020
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41. The nuclear receptor FXR inhibits Glucagon-Like Peptide-1 secretion in response to microbiota-derived Short-Chain Fatty Acids.

Author

Ducastel S, Touche V, Trabelsi MS, Boulinguiez A, Butruille L, Nawrot M, Peschard S, Chávez-Talavera O, Dorchies E, Vallez E, Annicotte JS, Lancel S, Briand O, Bantubungi K, Caron S, Bindels LB, Delzenne NM, Tailleux A, Staels B, and Lestavel S

Subjects
Animals, Colon drug effects, Glucagon-Like Peptide 1 metabolism, Male, Mice, Mice, Inbred C57BL, Mice, Knockout, Receptors, G-Protein-Coupled genetics, Receptors, G-Protein-Coupled metabolism, Colon metabolism, Fatty Acids, Volatile pharmacology, Glucagon-Like Peptide 1 antagonists & inhibitors, Microbiota, Receptors, Cytoplasmic and Nuclear physiology
Abstract

The gut microbiota participates in the control of energy homeostasis partly through fermentation of dietary fibers hence producing short-chain fatty acids (SCFAs), which in turn promote the secretion of the incretin Glucagon-Like Peptide-1 (GLP-1) by binding to the SCFA receptors FFAR2 and FFAR3 on enteroendocrine L-cells. We have previously shown that activation of the nuclear Farnesoid X Receptor (FXR) decreases the L-cell response to glucose. Here, we investigated whether FXR also regulates the SCFA-induced GLP-1 secretion. GLP-1 secretion in response to SCFAs was evaluated ex vivo in murine colonic biopsies and in colonoids of wild-type (WT) and FXR knock-out (KO) mice, in vitro in GLUTag and NCI-H716 L-cells activated with the synthetic FXR agonist GW4064 and in vivo in WT and FXR KO mice after prebiotic supplementation. SCFA-induced GLP-1 secretion was blunted in colonic biopsies from GW4064-treated mice and enhanced in FXR KO colonoids. In vitro FXR activation inhibited GLP-1 secretion in response to SCFAs and FFAR2 synthetic ligands, mainly by decreasing FFAR2 expression and downstream Gαq-signaling. FXR KO mice displayed elevated colonic FFAR2 mRNA levels and increased plasma GLP-1 levels upon local supply of SCFAs with prebiotic supplementation. Our results demonstrate that FXR activation decreases L-cell GLP-1 secretion in response to inulin-derived SCFA by reducing FFAR2 expression and signaling. Inactivation of intestinal FXR using bile acid sequestrants or synthetic antagonists in combination with prebiotic supplementation may be a promising therapeutic approach to boost the incretin axis in type 2 diabetes.

Published
2020
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42. Postprandial Circulating miRNAs in Response to a Dietary Fat Challenge.

Author

Mantilla-Escalante DC, López de Las Hazas MC, Gil-Zamorano J, Del Pozo-Acebo L, Crespo MC, Martín-Hernández R, Del Saz A, Tomé-Carneiro J, Cardona F, Cornejo-Pareja I, García-Ruiz A, Briand O, Lasunción MA, Visioli F, and Dávalos A

Subjects
Animals, Humans, Mice, Real-Time Polymerase Chain Reaction, Signal Transduction drug effects, Circulating MicroRNA blood, Dietary Fats adverse effects, Hyperlipidemias etiology, Postprandial Period drug effects
Abstract

Postprandial lipemia has many physiopathological effects, some of which increase the risk of cardiovascular disease. MicroRNAs (miRNAs) can be found in almost all biological fluids, but their postprandial kinetics are poorly described. We aimed to profile circulating miRNAs in response to a fat challenge. In total, 641 circulating miRNAs were assessed by real-time PCR in plasmas from mice two hours after lipid gavage. Mice with intestine-specific loss of Dicer were screened to identify potential miRNAs released by the intestine. A total of 68 miRNAs were selected for further validation. Ten circulating miRNAs were finally validated as responsive to postprandial lipemia, including miR-206-3p, miR-543-3p, miR-466c-5p, miR-27b-5p, miR-409-3p, miR-340-3p, miR-1941-3p, miR-10a-3p, miR-125a-3p, and miR-468-3p. Analysis of their possible tissues of origin/target showed an enrichment of selected miRNAs in liver, intestine, brain, or skeletal muscle. miR-206, miR-27b-5p, and miR-409-3p were validated in healthy humans. Analysis of their predicted target genes revealed their potential involvement in insulin/insulin like growth factor (insulin/IGF), angiogenesis, cholecystokinin B receptor signaling pathway (CCKR), inflammation or Wnt pathways for mice, and in platelet derived growth factor (PDGF) and CCKR signaling pathways for humans. Therefore, the current study shows that certain miRNAs are released in the circulation in response to fatty meals, proposing them as potential novel therapeutic targets of lipid metabolism.

Published
2019
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43. Endospanin-2 enhances skeletal muscle energy metabolism and running endurance capacity.

Author

Lancel S, Hesselink MK, Woldt E, Rouillé Y, Dorchies E, Delhaye S, Duhem C, Thorel Q, Mayeuf-Louchart A, Pourcet B, Montel V, Schaart G, Beton N, Picquet F, Briand O, Salles JP, Duez H, Schrauwen P, Bastide B, Bailleul B, Staels B, and Sebti Y

Subjects
Adaptor Proteins, Signal Transducing genetics, Adaptor Proteins, Signal Transducing physiology, Animals, Autophagy, Caloric Restriction, Cell Plasticity genetics, Cells, Cultured, Extracellular Signal-Regulated MAP Kinases metabolism, Female, Humans, Intracellular Signaling Peptides and Proteins, MAP Kinase Signaling System, Male, Membrane Proteins genetics, Mice, Mitochondria metabolism, Muscle Fibers, Fast-Twitch physiology, Muscle Fibers, Slow-Twitch physiology, Muscle, Skeletal cytology, Muscle, Skeletal physiology, Oxidative Stress, Phenotype, Phosphorylation, Physical Exertion, RNA, Messenger metabolism, Energy Metabolism, Membrane Proteins physiology, Muscle, Skeletal metabolism, Physical Endurance physiology
Abstract

Metabolic stresses such as dietary energy restriction or physical activity exert beneficial metabolic effects. In the liver, endospanin-1 and endospanin-2 cooperatively modulate calorie restriction-mediated (CR-mediated) liver adaptations by controlling growth hormone sensitivity. Since we found CR to induce endospanin protein expression in skeletal muscle, we investigated their role in this tissue. In vivo and in vitro endospanin-2 triggers ERK phosphorylation in skeletal muscle through an autophagy-dependent pathway. Furthermore, endospanin-2, but not endospanin-1, overexpression decreases muscle mitochondrial ROS production, induces fast-to-slow fiber-type switch, increases skeletal muscle glycogen content, and improves glucose homeostasis, ultimately promoting running endurance capacity. In line, endospanin-2-/- mice display higher lipid peroxidation levels, increased mitochondrial ROS production under mitochondrial stress, decreased ERK phosphorylation, and reduced endurance capacity. In conclusion, our results identify endospanin-2 as a potentially novel player in skeletal muscle metabolism, plasticity, and function.

Published
2018
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44. Hair analysis for the biomonitoring of pesticide exposure: comparison with blood and urine in a rat model.

Author

Appenzeller BMR, Hardy EM, Grova N, Chata C, Faÿs F, Briand O, Schroeder H, and Duca RC

Subjects
Animals, Environmental Exposure analysis, Environmental Pollutants pharmacokinetics, Female, Pesticides pharmacokinetics, Rats, Rats, Long-Evans, Reproducibility of Results, Environmental Monitoring methods, Environmental Pollutants analysis, Hair chemistry, Pesticides analysis
Abstract

Urine and plasma have been used to date for the biomonitoring of exposure to pollutants and are still the preferred fluids for this purpose; however, these fluids mainly provide information on the short term and may present a high level of variability regarding pesticide concentrations, especially for nonpersistent compounds. Hair analysis may provide information about chronic exposure that is averaged over several months; therefore, this method has been proposed as an alternative to solely relying on these fluids. Although the possibility of detecting pesticides in hair has been demonstrated over the past few years, the unknown linkage between exposure and pesticides concentration in hair has limited the recognition of this matrix as a relevant tool for assessing human exposure. Based on a rat model in which there was controlled exposure to a mixture of pesticides composed of lindane, β-hexachlorocyclohexane, β-endosulfan, p,p'-DDT, p,p'-DDE, dieldrin, pentachlorophenol, diazinon, chlorpyrifos, cyhalothrin, permethrin, cypermethrin, propiconazole, fipronil, oxadiazon, diflufenican, trifluralin, carbofuran, and propoxur, the current work demonstrates the association between exposure intensity and resulting pesticide concentration in hair. We also compared the results obtained from a hair analysis to urine and plasma collected from the same rats. Hair, blood, and urine were collected from rats submitted to 90-day exposure by gavage to the aforementioned mixture of common pesticides at different levels. We observed a linear relationship between exposure intensity and the concentration of pesticides in the rats' hair (R Pearson 0.453-0.978, p < 0.01). A comparison with results from urine and plasma samples demonstrated the relevance of hair analysis and, for many chemicals, its superiority over using fluids for differentiating animals from different groups and for re-attributing animals to their correct groups of exposure based on pesticide concentrations in the matrix. Therefore, this study strongly supports hair analysis as a reliable tool to be used during epidemiological studies to investigate exposure-associated adverse health effects.

Published
2017
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45. Retrograde cholesterol transport in the human Caco-2/TC7 cell line: a model to study trans-intestinal cholesterol excretion in atherogenic and diabetic dyslipidemia.

Author

Dugardin C, Briand O, Touche V, Schonewille M, Moreau F, Le May C, Groen AK, Staels B, and Lestavel S

Subjects
Caco-2 Cells, Dyslipidemias etiology, Humans, Atherosclerosis complications, Cholesterol metabolism, Diabetes Mellitus, Type 2 complications, Dyslipidemias metabolism, Enterocytes metabolism, Exocytosis
Abstract

Aims: The dyslipidemia associated with type 2 diabetes is a major risk factor for the development of atherosclerosis. Trans-intestinal cholesterol excretion (TICE) has recently been shown to contribute, together with the classical hepatobiliary route, to fecal cholesterol excretion and cholesterol homeostasis. The aim of this study was to develop an in vitro cell model to investigate enterocyte-related processes of TICE., Methods: Differentiated Caco-2/TC7 cells were grown on transwells and incubated basolaterally (blood side) with human plasma and apically (luminal side) with lipid micelles. Radioactive and fluorescent cholesterol tracers were used to investigate cholesterol uptake at the basolateral membrane, intracellular distribution and apical excretion., Results: Our results show that cholesterol is taken up at the basolateral membrane, accumulates intracellularly as lipid droplets and undergoes a cholesterol acceptor-facilitated and progressive excretion through the apical membrane of enterocytes. The overall process is abolished at 4 °C, suggesting a biologically active phenomenon. Moreover, this trans-enterocytic retrograde cholesterol transport displays some TICE features like modulation by PCSK9 and an ABCB1 inhibitor. Finally, we highlight the involvement of microtubules in the transport of plasma cholesterol from basolateral to apical pole of enterocytes., Conclusions: The human Caco-2/TC7 cell line appears a good in vitro model to investigate the enterocytic molecular mechanisms of TICE, which may help to identify intestinal molecular targets to enhance reverse cholesterol transport and fight against dyslipidemia.

Published
2017
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46. Liver X Receptor Regulates Triglyceride Absorption Through Intestinal Down-regulation of Scavenger Receptor Class B, Type 1.

Author

Briand O, Touche V, Colin S, Brufau G, Davalos A, Schonewille M, Bovenga F, Carrière V, de Boer JF, Dugardin C, Riveau B, Clavey V, Tailleux A, Moschetta A, Lasunción MA, Groen AK, Staels B, and Lestavel S

Subjects
Animals, Apolipoprotein B-100 metabolism, Apolipoproteins B metabolism, Benzoates pharmacology, Benzylamines pharmacology, Caco-2 Cells, Cholesterol, Dietary metabolism, Chylomicrons metabolism, DEAD-box RNA Helicases deficiency, DEAD-box RNA Helicases genetics, Down-Regulation, Humans, Hydrocarbons, Fluorinated pharmacology, Intestinal Mucosa drug effects, Jejunum drug effects, Liver X Receptors, Male, Mice, Inbred C57BL, Mice, Knockout, MicroRNAs genetics, MicroRNAs metabolism, Orphan Nuclear Receptors agonists, Protein Transport, RNA Interference, Ribonuclease III deficiency, Ribonuclease III genetics, Scavenger Receptors, Class B deficiency, Scavenger Receptors, Class B genetics, Signal Transduction, Sulfonamides pharmacology, Transcription, Genetic, Transfection, Intestinal Absorption drug effects, Intestinal Mucosa metabolism, Jejunum metabolism, Orphan Nuclear Receptors metabolism, Scavenger Receptors, Class B metabolism, Triglycerides metabolism
Abstract

Background & Aims: Reducing postprandial triglyceridemia may be a promising strategy to lower the risk of cardiovascular disorders associated with obesity and type 2 diabetes. In enterocytes, scavenger receptor class B, type 1 (SR-B1, encoded by SCARB1) mediates lipid-micelle sensing to promote assembly and secretion of chylomicrons. The nuclear receptor subfamily 1, group H, members 2 and 3 (also known as liver X receptors [LXRs]) regulate genes involved in cholesterol and fatty acid metabolism. We aimed to determine whether intestinal LXRs regulate triglyceride absorption., Methods: C57BL/6J mice were either fed a cholesterol-enriched diet or given synthetic LXR agonists (GW3965 or T0901317). We measured the production of chylomicrons and localized SR-B1 by immunohistochemistry. Mechanisms of postprandial triglyceridemia and SR-B1 regulation were studied in Caco-2/TC7 cells incubated with LXR agonists., Results: In mice and in the Caco-2/TC7 cell line, LXR agonists caused localization of intestinal SR-B1 from apical membranes to intracellular organelles and reduced chylomicron secretion. In Caco-2/TC7 cells, LXR agonists reduced SR-B1-dependent lipidic-micelle-induced Erk phosphorylation. LXR agonists also reduced intracellular trafficking of the apical apolipoprotein B pool toward secretory compartments. LXR reduced levels of SR-B1 in Caco-2/TC7 cells via a post-transcriptional mechanism that involves microRNAs., Conclusion: In Caco-2/TC7 cells and mice, intestinal activation of LXR reduces the production of chylomicrons by a mechanism dependent on the apical localization of SR-B1., (Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Published
2016
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47. Development of the Sanofi Pasteur tetravalent dengue vaccine: One more step forward.

Author

Guy B, Briand O, Lang J, Saville M, and Jackson N

Subjects
Animals, Dengue epidemiology, Dengue Vaccines adverse effects, Drug Discovery methods, Drug Evaluation, Preclinical, Drug-Related Side Effects and Adverse Reactions, Humans, Immunization Schedule, Treatment Outcome, Vaccines, Attenuated adverse effects, Vaccines, Attenuated immunology, Vaccines, Attenuated isolation & purification, Clinical Trials as Topic, Dengue prevention & control, Dengue Vaccines immunology, Dengue Vaccines isolation & purification
Abstract

Sanofi Pasteur has developed a recombinant, live-attenuated, tetravalent dengue vaccine (CYD-TDV) that is in late-stage development. The present review summarizes the different steps in the development of this dengue vaccine, with a particular focus on the clinical data from three efficacy trials, which includes one proof-of-concept phase IIb (NCT00842530) and two pivotal phase III efficacy trials (NCT01373281 and NCT01374516). Earlier studies showed that the CYD-TDV candidate had a satisfactory safety profile and was immunogenic across the four vaccine serotypes in both in vitro and in vivo preclinical tests, as well as in initial phase I to phase II clinical trials in both flavivirus-naïve and seropositive individuals. Data from the 25 months (after the first injection) active phase of the two pivotal phase III efficacy studies shows that CYD-TDV (administered at 0, 6, and 12 months) is efficacious against virologically-confirmed disease (primary endpoint) and has a good safety profile. Secondary analyses also showed efficacy against all four dengue serotypes and protection against severe disease and hospitalization. The end of the active phases in these studies completes more than a decade of development of CYD-TDV, but considerable activities and efforts remain to address outstanding scientific, clinical, and immunological questions, while preparing for the introduction and use of CYD-TDV. Additional safety observations were recently reported from the first complete year of hospital phase longer term surveillance for two phase 3 studies and the first and second completed years for one phase 2b study, demonstrating the optimal age for intervention from 9 years. Dengue is a complex disease, and both short-term and long-term safety and efficacy will continue to be addressed by ongoing long-term follow-up and future post-licensure studies., (Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Published
2015
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48. Farnesoid X receptor inhibits glucagon-like peptide-1 production by enteroendocrine L cells.

Author

Trabelsi MS, Daoudi M, Prawitt J, Ducastel S, Touche V, Sayin SI, Perino A, Brighton CA, Sebti Y, Kluza J, Briand O, Dehondt H, Vallez E, Dorchies E, Baud G, Spinelli V, Hennuyer N, Caron S, Bantubungi K, Caiazzo R, Reimann F, Marchetti P, Lefebvre P, Bäckhed F, Gribble FM, Schoonjans K, Pattou F, Tailleux A, Staels B, and Lestavel S

Subjects
Animals, Anticholesteremic Agents pharmacology, Basic Helix-Loop-Helix Leucine Zipper Transcription Factors metabolism, Bile Acids and Salts metabolism, Blood Glucose metabolism, Colesevelam Hydrochloride pharmacology, Colon cytology, Colon metabolism, Diet, High-Fat, Glucagon-Like Peptide 1 metabolism, Glycolysis, Humans, Ileum cytology, Ileum metabolism, Insulin metabolism, Insulin Secretion, Insulin-Secreting Cells metabolism, Intestines cytology, Jejunum cytology, Jejunum metabolism, Mice, Mice, Knockout, Mice, Obese, Nuclear Proteins metabolism, Obesity genetics, Obesity metabolism, Proglucagon drug effects, Proglucagon genetics, Proglucagon metabolism, Receptors, G-Protein-Coupled genetics, Sequestering Agents pharmacology, Signal Transduction, Transcription Factors metabolism, Enteroendocrine Cells metabolism, Glucagon-Like Peptide 1 genetics, Intestinal Mucosa metabolism, RNA, Messenger metabolism, Receptors, Cytoplasmic and Nuclear genetics
Abstract

Bile acids are signalling molecules, which activate the transmembrane receptor TGR5 and the nuclear receptor FXR. BA sequestrants (BAS) complex bile acids in the intestinal lumen and decrease intestinal FXR activity. The BAS-BA complex also induces glucagon-like peptide-1 (GLP-1) production by L cells which potentiates β-cell glucose-induced insulin secretion. Whether FXR is expressed in L cells and controls GLP-1 production is unknown. Here, we show that FXR activation in L cells decreases proglucagon expression by interfering with the glucose-responsive factor Carbohydrate-Responsive Element Binding Protein (ChREBP) and GLP-1 secretion by inhibiting glycolysis. In vivo, FXR deficiency increases GLP-1 gene expression and secretion in response to glucose hence improving glucose metabolism. Moreover, treatment of ob/ob mice with the BAS colesevelam increases intestinal proglucagon gene expression and improves glycaemia in a FXR-dependent manner. These findings identify the FXR/GLP-1 pathway as a new mechanism of BA control of glucose metabolism and a pharmacological target for type 2 diabetes.

Published
2015
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49. Analysis of airborne pesticides from different chemical classes adsorbed on Radiello® Tenax® passive tubes by thermal-desorption-GC/MS.

Author

Raeppel C, Fabritius M, Nief M, Appenzeller BM, Briand O, Tuduri L, and Millet M

Subjects
Adsorption, France, Gas Chromatography-Mass Spectrometry, Air Pollutants analysis, Herbicides analysis, Polymers chemistry
Abstract

An analytical methodology using automatic thermal desorption (ATD) and GC/MS was developed for the determination of 28 pesticides of different chemical classes (dichlobenil, carbofuran, trifluralin, clopyralid, carbaryl, flazasulfuron, mecoprop-P, dicamba, 2,4-MCPA, dichlorprop, 2,4-D, triclopyr, cyprodinil, bromoxynil, fluroxypyr, oxadiazon, myclobutanil, buprofezin, picloram, trinexapac-p-ethyl, ioxynil, diflufenican, tebuconazole, bifenthrin, isoxaben, alphacypermethrin, fenoxaprop and tau-fluvalinate) commonly used in nonagricultural areas in atmospheric samples. This methodology was developed to evaluate the indoor and outdoor atmospheric contamination by nonagricultural pesticides. Pesticides were sampled passive sampling tubes containing Tenax® adsorbent. Since most of these pesticides are polar (clopyralid, mecoprop-P, dicamba, 2,4-MCPA, dichlorprop, 2,4-D, triclopyr, bromoxynil, fluroxypyr, picloram, trinexapac-p-ethyl and ioxynil), a derivatisation step is required. For this purpose, a silylation step using N-(t-butyldimethylsilyl)-N-methyltrifluoroacetamide (MtBSTFA) was added before thermal desorption. This agent was chosen since it delivers very specific ions on electronic impact (m/z = M-57). This method was established with special consideration for optimal thermal desorption conditions (desorption temperature, desorb flow and duration; trap heating duration and flow; outlet split), linear ranges, limits of quantification and detection which varied from 0.005 to 10 ng and from 0.001 to 2.5 ng, respectively, for an uncertainty varied from 8 to 30 %. The method was applied in situ to the analysis of passive tubes exposed during herbicide application to an industrial site in east of France.

Published
2015
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50. Activation of intestinal peroxisome proliferator-activated receptor-α increases high-density lipoprotein production.

Author

Colin S, Briand O, Touche V, Wouters K, Baron M, Pattou F, Hanf R, Tailleux A, Chinetti G, Staels B, and Lestavel S

Subjects
Animals, Apolipoproteins B metabolism, Butyrates pharmacology, Caco-2 Cells, Cells, Cultured, Chalcones pharmacology, Enterocytes metabolism, Esterification physiology, Fatty Acids metabolism, Female, Humans, Jejunum metabolism, Mice, Mice, Knockout, PPAR alpha antagonists & inhibitors, Phenylurea Compounds pharmacology, Propionates pharmacology, Lipoproteins, HDL metabolism, PPAR alpha physiology
Abstract

Aims: Peroxisome proliferator-activated receptor (PPAR)-α is a transcription factor controlling lipid metabolism in liver, heart, muscle, and macrophages. Peroxisome proliferator-activated receptor-α activation increases plasma HDL cholesterol and exerts hypotriglyceridaemic actions via the liver. However, the intestine expresses PPAR-α, produces HDL and chylomicrons, and is exposed to diet-derived PPAR-α ligands. Therefore, we examined the effects of PPAR-α activation on intestinal lipid and lipoprotein metabolism., Methods and Results: The impact of PPAR-α activation was evaluated in term of HDL-related gene expression in mice, ex vivo in human jejunal biopsies and in Caco-2/TC7 cells. Apolipoprotein-AI/HDL secretion, cholesterol esterification, and trafficking were also studied in vitro. In parallel to improving plasma lipid profiles and increasing liver and intestinal expression of fatty acid oxidation genes, treatment with the dual PPAR-α/δ ligand GFT505 resulted in a more pronounced increase in plasma HDL compared with fenofibrate in mice. GFT505, but not fenofibrate, increased the expression of HDL production genes such as apolipoprotein-AI and ATP-binding cassette A1 transporter in murine intestines. A similar increase was observed upon PPAR-α activation of human biopsies and Caco-2/TC7 cells. Additionally, HDL secretion by Caco-2/TC7 cells increased. Moreover, PPAR-α activation decreased the cholesterol esterification capacity of Caco-2/TC7 cells, modified cholesterol trafficking, and reduced apolipoprotein-B secretion., Conclusion: Peroxisome proliferator-activated receptor-α activation reduces cholesterol esterification, suppresses chylomicron, and increases HDL secretion by enterocytes. These results identify the intestine as a target organ of PPAR-α ligands with entero-hepatic tropism to reduce atherogenic dyslipidaemia.

Published
2013
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