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1. Additional file 19 of Enhancer promoter interactome and Mendelian randomization identify network of druggable vascular genes in coronary artery disease

Author

Chignon, Arnaud, Mathieu, Samuel, Rufiange, Anne, Argaud, D��borah, Voisine, Pierre, Boss��, Yohan, Arsenault, Benoit J., Th��riault, S��bastien, and Mathieu, Patrick

Abstract

Additional file 19. Supplemental Figure 1: Individual significant SNPs and 3D mapping in enhancer-promoter HiChIP.

Published
2022
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6. Considerations and consequences of allowing DNA sequence data as types of fungal taxa

Author

Zamora, J. C. (Juan Carlos), Svensson, M. (Mans), Kirschner, R. (Roland), Olariaga, I. (Ibai), Ryman, S. (Svengunnar), Alberto Parra, L. (Luis), Geml, J. (Jozsef), Rosling, A. (Anna), Adamcik, S. (Slavomir), Ahti, T. (Teuvo), Aime, M. C. (M. Catherine), Ainsworth, A. M. (A. Martyn), Albert, L. (Laszlo), Alberto, E. (Edgardo), Garcia, A. A. (Alberto Altes), Ageev, D. (Dmitry), Agerer, R. (Reinhard), Aguirre-Hudson, B. (Begona), Ammirati, J. (Joe), Andersson, H. (Harry), Angelini, C. (Claudio), Antonin, V. (Vladimir), Aoki, T. (Takayuki), Aptroot, A. (Andre), Argaud, D. (Didier), Sosa, B. I. (Blanca Imelda Arguello), Aronsen, A. (Arne), Arup, U. (Ulf), Asgari, B. (Bita), Assyov, B. (Boris), Atienza, V. (Violeta), Bandini, D. (Ditte), Baptista-Ferreira, J. L. (Joao Luis), Baral, H.-O. (Hans-Otto), Baroni, T. (Tim), Barreto, R. W. (Robert Weingart), Baker, H. (Henry), Bell, A. (Ann), Bellanger, J.-M. (Jean-Michel), Bellu, F. (Francesco), Bemmann, M. (Martin), Bendiksby, M. (Mika), Bendiksen, E. (Egil), Bendiksen, K. (Katriina), Benedek, L. (Lajos), Beresova-Guttova, A. (Anna), Berger, F. (Franz), Berndt, R. (Reinhard), Bernicchia, A. (Annarosa), Biketova, A. Y. (Alona Yu), Bizio, E. (Enrico), Bjork, C. (Curtis), Boekhout, T. (Teun), Boertmann, D. (David), Bohning, T. (Tanja), Boittin, F. (Florent), Boluda, C. G. (Carlos G.), Boomsluiter, M. W. (Menno W.), Borovicka, J. (Jan), Brandrud, T. E. (Tor Erik), Braun, U. (Uwe), Brodo, I. (Irwin), Bulyonkova, T. (Tatiana), Burdsall, H. H. (Harold H., Jr.), Buyck, B. (Bart), Burgaz, A. R. (Ana Rosa), Calatayud, V. (Vicent), Callac, P. (Philippe), Campo, E. (Emanuele), Candusso, M. (Massimo), Capoen, B. (Brigitte), Carbo, J. (Joaquim), Carbone, M. (Matteo), Castaneda-Ruiz, R. F. (Rafael F.), Castellano, M. A. (Michael A.), Chen, J. (Jie), Clerc, P. (Philippe), Consiglio, G. (Giovanni), Corriol, G. (Gilles), Courtecuisse, R. (Regis), Crespo, A. (Ana), Cripps, C. (Cathy), Crous, P. W. (Pedro W.), da Silva, G. A. (Gladstone Alves), da Silva, M. (Meiriele), Dam, M. (Marjo), Dam, N. (Nico), Dammrich, F. (Frank), Das, K. (Kanad), Davies, L. (Linda), De Crop, E. (Eske), De Kesel, A. (Andre), De Lange, R. (Ruben), Bonzi, B. D. (Barbara De Madrignac), dela Cruz, T. E. (Thomas Edison E.), Delgat, L. (Lynn), Demoulin, V. (Vincent), Desjardin, D. E. (Dennis E.), Diederich, P. (Paul), Dima, B. (Balint), Dios, M. M. (Maria Martha), Divakar, P. K. (Pradeep Kumar), Douanla-Meli, C. (Clovis), Douglas, B. (Brian), Drechsler-Santos, E. R. (Elisandro Ricardo), Dyer, P. S. (Paul S.), Eberhardt, U. (Ursula), Ertz, D. (Damien), Esteve-Raventos, F. (Fernando), Salazar, J. A. (Javier Angel Etayo), Evenson, V. (Vera), Eyssartier, G. (Guillaume), Farkas, E. (Edit), Favre, A. (Alain), Fedosova, A. G. (Anna G.), Filippa, M. (Mario), Finy, P. (Peter), Flakus, A. (Adam), Fos, S. (Simon), Fournier, J. (Jacques), Fraiture, A. (Andre), Franchi, P. (Paolo), Molano, A. E. (Ana Esperanza Franco), Friebes, G. (Gernot), Frisch, A. (Andreas), Fryday, A. (Alan), Furci, G. (Giuliana), Marquez, R. G. (Ricardo Galan), Garbelotto, M. (Matteo), Garcia-Martin, J. M. (Joaquina Maria), Otalora, M. A. (Monica A. Garcia), Sanchez, D. G. (Dania Garcia), Gardiennet, A. (Alain), Garnica, S. (Sigisfredo), Benavent, I. G. (Isaac Garrido), Gates, G. (Genevieve), Gerlach, A. d. (Alice da Cruz Lima), Ghobad-Nejhad, M. (Masoomeh), Gibertoni, T. B. (Tatiana B.), Grebenc, T. (Tine), Greilhuber, I. (Irmgard), Grishkan, B. (Bella), Groenewald, J. Z. (Johannes Z.), Grube, M. (Martin), Gruhn, G. (Gerald), Gueidan, C. (Cecile), Gulden, G. (Gro), Gusmao, L. F. (Luis F. P.), Hafellner, J. (Josef), Hairaud, M. (Michel), Halama, M. (Marek), Hallenberg, N. (Nils), Halling, R. E. (Roy E.), Hansen, K. (Karen), Harder, C. B. (Christoffer Bugge), Heilmann-Clausen, J. (Jacob), Helleman, S. (Stip), Henriot, A. (Alain), Hernandez-Restrepo, M. (Margarita), Herve, R. (Raphael), Hobart, C. (Caroline), Hoffmeister, M. (Mascha), Hoiland, K. (Klaus), Holec, J. (Jan), Holien, H. (Hakon), Hughes, K. (Karen), Hubka, V. (Vit), Huhtinen, S. (Seppo), Ivancevic, B. (Boris), Jagers, M. (Marian), Jaklitsch, W. (Walter), Jansen, A. (AnnaElise), Jayawardena, R. S. (Ruvishika S.), Jeppesen, T. S. (Thomas Stjernegaard), Jeppson, M. (Mikael), Johnston, P. (Peter), Jorgensen, P. M. (Per Magnus), Karnefelt, I. (Ingvar), Kalinina, L. B. (Liudmila B.), Kantvilas, G. (Gintaras), Karadelev, M. (Mitko), Kasuya, T. (Taiga), Kautmanova, I. (Ivona), Kerrigan, R. W. (Richard W.), Kirchmair, M. (Martin), Kiyashko, A. (Anna), Knapp, D. G. (Daniel G.), Knudsen, H. (Henning), Knudsen, K. (Kerry), Knutsson, T. (Tommy), Kolarik, M. (Miroslav), Koljalg, U. (Urmas), Kosuthova, A. (Alica), Koszka, A. (Attila), Kotiranta, H. (Heikki), Kotkova, V. (Vera), Koukol, O. (Ondrej), Kout, J. (Jiri), Kovacs, G. M. (Gabor M.), Kriz, M. (Martin), Kruys, A. (Asa), Kudera, V. (Viktor), Kudzma, L. (Linas), Kuhar, F. (Francisco), Kukwa, M. (Martin), Kumar, T. K. (T. K. Arun), Kunca, V. (Vladimir), Kusan, I. (Ivana), Kuyper, T. W. (Thomas W.), Lado, C. (Carlos), Laessoe, T. (Thomas), Laine, P. (Patrice), Langer, E. (Ewald), Larsson, E. (Ellen), Larsson, K.-H. (Karl-Henrik), Laursen, G. (Gary), Lechat, C. (Christian), Lee, S. (Serena), Lendemer, J. C. (James C.), Levin, L. (Laura), Lindemann, U. (Uwe), Lindstrom, H. (Hakan), Liu, X. (Xingzhong), Hernandez, R. C. (Regulo Carlos Llarena), Llop, E. (Esteve), Locsmandi, C. (Csaba), Lodge, D. J. (Deborah Jean), Loizides, M. (Michael), Lokos, L. (Laszlo), Luangsa-ard, J. (Jennifer), Luderitz, M. (Matthias), Lumbsch, T. (Thorsten), Lutz, M. (Matthias), Mahoney, D. (Dan), Malysheva, E. (Ekaterina), Malysheva, V. (Vera), Manimohan, P. (Patinjareveettil), Mann-Felix, Y. (Yasmina), Marques, G. (Guilhermina), Martinez-Gil, R. (Ruben), Marson, G. (Guy), Mata, G. (Gerardo), Matheny, P. B. (P. Brandon), Mathiassen, G. H. (Geir Harald), Matocec, N. (Neven), Mayrhofer, H. (Helmut), Mehrabi, M. (Mehdi), Melo, I. (Ireneia), Mesic, A. (Armin), Methven, A. S. (Andrew S.), Miettinen, O. (Otto), Romero, A. M. (Ana M. Millanes), Miller, A. N. (Andrew N.), Mitchell, J. K. (James K.), Moberg, R. (Roland), Moreau, P.-A. (Pierre-Arthur), Moreno, G. (Gabriel), Morozova, O. (Olga), Morte, A. (Asuncion), Muggia, L. (Lucia), Gonzalez, G. M. (Guillermo Munoz), Myllys, L. (Leena), Nagy, I. (Istvan), Nagy, L. G. (Laszlo G.), Neves, M. A. (Maria Alice), Niemela, T. (Tuomo), Nimis, P. L. (Pier Luigi), Niveiro, N. (Nicolas), Noordeloos, M. E. (Machiel E.), Nordin, A. (Anders), Noumeur, S. R. (Sara Raouia), Novozhilov, Y. (Yuri), Nuytinck, J. (Jorinde), Ohenoja, E. (Esteri), Fiuza, P. O. (Patricia Oliveira), Orange, A. (Alan), Ordynets, A. (Alexander), Ortiz-Santana, B. (Beatriz), Pacheco, L. (Leticia), Pal-Fam, F. (Ferenc), Palacio, M. (Melissa), Palice, Z. (Zdenek), Papp, V. (Viktor), Partel, K. (Kadri), Pawlowska, J. (Julia), Paz, A. (Aurelia), Peintner, U. (Ursula), Pennycook, S. (Shaun), Pereira, O. L. (Olinto Liparini), Daniels, P. P. (Pablo Perez), Capella, M. A. (Miguel A. Perez-De-Gregorio), del Amo, C. M. (Carlos Manuel Perez), Gorjon, S. P. (Sergio Perez), Perez-Ortega, S. (Sergio), Perez-Vargas, I. (Israel), Perry, B. A. (Brian A.), Petersen, J. H. (Jens H.), Petersen, R. H. (Ronald H.), Pfister, D. H. (Donald H.), Phukhamsakda, C. (Chayanard), Piatek, M. (Marcin), Piepenbring, M. (Meike), Pino-Bodas, R. (Raquel), Esquivel, J. P. (Juan Pablo Pinzon), Pirot, P. (Paul), Popov, E. S. (Eugene S.), Popoff, O. (Orlando), Alvaro, M. P. (Maria Prieto), Printzen, C. (Christian), Psurtseva, N. (Nadezhda), Purahong, W. (Witoon), Quijada, L. (Luis), Rambold, G. (Gerhard), Ramirez, N. A. (Natalia A.), Raja, H. (Huzefa), Raspe, O. (Olivier), Raymundo, T. (Tania), Reblova, M. (Martina), Rebriev, Y. A. (Yury A.), Garcia, J. d. (Juan de Dios Reyes), Ripoll, M. A. (Miguel Angel Ribes), Richard, F. (Franck), Richardson, M. J. (Mike J.), Rico, V. J. (Victor J.), Robledo, G. L. (Gerardo Lucio), Barbosa, F. R. (Flavia Rodrigues), Rodriguez-Caycedo, C. (Cristina), Rodriguez-Flakus, P. (Pamela), Ronikier, A. (Anna), Casas, L. R. (Luis Rubio), Rusevska, K. (Katerina), Saar, G. (Gunter), Saar, I. (Irja), Salcedo, I. (Isabel), Martinez, S. M. (Sergio M. Salcedo), Montoya, C. A. (Carlos A. Salvador), Sanchez-Ramirez, S. (Santiago), Sandoval-Sierra, J. V. (J. Vladimir), Santamaria, S. (Sergi), Monteiro, J. S. (Josiane Santana), Schroers, H. J. (Hans Josef), Schulz, B. (Barbara), Schmidt-Stohn, G. (Geert), Schumacher, T. (Trond), Senn-Irlet, B. (Beatrice), Sevcikova, H. (Hana), Shchepin, O. (Oleg), Shirouzu, T. (Takashi), Shiryaev, A. (Anton), Siepe, K. (Klaus), Sir, E. B. (Esteban B.), Sohrabi, M. (Mohammad), Soop, K. (Karl), Spirin, V. (Viacheslav), Spribille, T. (Toby), Stadler, M. (Marc), Stalpers, J. (Joost), Stenroos, S. (Soili), Suija, A. (Ave), Sunhede, S. (Stellan), Svantesson, S. (Sten), Svensson, S. (Sigvard), Svetasheva, T. Y. (Tatyana Yu), Swierkosz, K. (Krzysztof), Tamm, H. (Heidi), Taskin, H. (Hatira), Taudiere, A. (Adrien), Tedebrand, J.-O. (Jan-Olof), Lahoz, R. T. (Raul Tena), Temina, M. (Marina), Thell, A. (Arne), Thines, M. (Marco), Thor, G. (Goren), Thus, H. (Holger), Tibell, L. (Leif), Tibell, S. (Sanja), Timdal, E. (Einar), Tkalcec, Z. (Zdenko), Tonsberg, T. (Tor), Trichies, G. (Gerard), Triebel, D. (Dagmar), Tsurykau, A. (Andrei), Tulloss, R. E. (Rodham E.), Tuovinen, V. (Veera), Sosa, M. U. (Miguel Ulloa), Urcelay, C. (Carlos), Valade, F. (Francois), Garza, R. V. (Ricardo Valenzuela), van den Boom, P. (Pieter), Van Vooren, N. (Nicolas), Vasco-Palacios, A. M. (Aida M.), Vauras, J. (Jukka), Santos, J. M. (Juan Manuel Velasco), Vellinga, E. (Else), Verbeken, A. (Annemieke), Vetlesen, P. (Per), Vizzini, A. (Alfredo), Voglmayr, H. (Hermann), Volobuev, S. (Sergey), von Brackel, W. (Wolfgang), Voronina, E. (Elena), Walther, G. (Grit), Watling, R. (Roy), Weber, E. (Evi), Wedin, M. (Mats), Weholt, O. (Oyvind), Westberg, M. (Martin), Yurchenko, E. (Eugene), Zehnalek, P. (Petr), Zhang, H. (Huang), Zhurbenko, M. P. (Mikhail P.), Ekmani, S. (Stefan), Zamora, J. C. (Juan Carlos), Svensson, M. (Mans), Kirschner, R. (Roland), Olariaga, I. (Ibai), Ryman, S. (Svengunnar), Alberto Parra, L. (Luis), Geml, J. (Jozsef), Rosling, A. (Anna), Adamcik, S. (Slavomir), Ahti, T. (Teuvo), Aime, M. C. (M. Catherine), Ainsworth, A. M. (A. Martyn), Albert, L. (Laszlo), Alberto, E. (Edgardo), Garcia, A. A. (Alberto Altes), Ageev, D. (Dmitry), Agerer, R. (Reinhard), Aguirre-Hudson, B. (Begona), Ammirati, J. (Joe), Andersson, H. (Harry), Angelini, C. (Claudio), Antonin, V. (Vladimir), Aoki, T. (Takayuki), Aptroot, A. (Andre), Argaud, D. (Didier), Sosa, B. I. (Blanca Imelda Arguello), Aronsen, A. (Arne), Arup, U. (Ulf), Asgari, B. (Bita), Assyov, B. (Boris), Atienza, V. (Violeta), Bandini, D. (Ditte), Baptista-Ferreira, J. L. (Joao Luis), Baral, H.-O. (Hans-Otto), Baroni, T. (Tim), Barreto, R. W. (Robert Weingart), Baker, H. (Henry), Bell, A. (Ann), Bellanger, J.-M. (Jean-Michel), Bellu, F. (Francesco), Bemmann, M. (Martin), Bendiksby, M. (Mika), Bendiksen, E. (Egil), Bendiksen, K. (Katriina), Benedek, L. (Lajos), Beresova-Guttova, A. (Anna), Berger, F. (Franz), Berndt, R. (Reinhard), Bernicchia, A. (Annarosa), Biketova, A. Y. (Alona Yu), Bizio, E. (Enrico), Bjork, C. (Curtis), Boekhout, T. (Teun), Boertmann, D. (David), Bohning, T. (Tanja), Boittin, F. (Florent), Boluda, C. G. (Carlos G.), Boomsluiter, M. W. (Menno W.), Borovicka, J. (Jan), Brandrud, T. E. (Tor Erik), Braun, U. (Uwe), Brodo, I. (Irwin), Bulyonkova, T. (Tatiana), Burdsall, H. H. (Harold H., Jr.), Buyck, B. (Bart), Burgaz, A. R. (Ana Rosa), Calatayud, V. (Vicent), Callac, P. (Philippe), Campo, E. (Emanuele), Candusso, M. (Massimo), Capoen, B. (Brigitte), Carbo, J. (Joaquim), Carbone, M. (Matteo), Castaneda-Ruiz, R. F. (Rafael F.), Castellano, M. A. (Michael A.), Chen, J. (Jie), Clerc, P. (Philippe), Consiglio, G. (Giovanni), Corriol, G. (Gilles), Courtecuisse, R. (Regis), Crespo, A. (Ana), Cripps, C. (Cathy), Crous, P. W. (Pedro W.), da Silva, G. A. (Gladstone Alves), da Silva, M. (Meiriele), Dam, M. (Marjo), Dam, N. (Nico), Dammrich, F. (Frank), Das, K. (Kanad), Davies, L. (Linda), De Crop, E. (Eske), De Kesel, A. (Andre), De Lange, R. (Ruben), Bonzi, B. D. (Barbara De Madrignac), dela Cruz, T. E. (Thomas Edison E.), Delgat, L. (Lynn), Demoulin, V. (Vincent), Desjardin, D. E. (Dennis E.), Diederich, P. (Paul), Dima, B. (Balint), Dios, M. M. (Maria Martha), Divakar, P. K. (Pradeep Kumar), Douanla-Meli, C. (Clovis), Douglas, B. (Brian), Drechsler-Santos, E. R. (Elisandro Ricardo), Dyer, P. S. (Paul S.), Eberhardt, U. (Ursula), Ertz, D. (Damien), Esteve-Raventos, F. (Fernando), Salazar, J. A. (Javier Angel Etayo), Evenson, V. (Vera), Eyssartier, G. (Guillaume), Farkas, E. (Edit), Favre, A. (Alain), Fedosova, A. G. (Anna G.), Filippa, M. (Mario), Finy, P. (Peter), Flakus, A. (Adam), Fos, S. (Simon), Fournier, J. (Jacques), Fraiture, A. (Andre), Franchi, P. (Paolo), Molano, A. E. (Ana Esperanza Franco), Friebes, G. (Gernot), Frisch, A. (Andreas), Fryday, A. (Alan), Furci, G. (Giuliana), Marquez, R. G. (Ricardo Galan), Garbelotto, M. (Matteo), Garcia-Martin, J. M. (Joaquina Maria), Otalora, M. A. (Monica A. Garcia), Sanchez, D. G. (Dania Garcia), Gardiennet, A. (Alain), Garnica, S. (Sigisfredo), Benavent, I. G. (Isaac Garrido), Gates, G. (Genevieve), Gerlach, A. d. (Alice da Cruz Lima), Ghobad-Nejhad, M. (Masoomeh), Gibertoni, T. B. (Tatiana B.), Grebenc, T. (Tine), Greilhuber, I. (Irmgard), Grishkan, B. (Bella), Groenewald, J. Z. (Johannes Z.), Grube, M. (Martin), Gruhn, G. (Gerald), Gueidan, C. (Cecile), Gulden, G. (Gro), Gusmao, L. F. (Luis F. P.), Hafellner, J. (Josef), Hairaud, M. (Michel), Halama, M. (Marek), Hallenberg, N. (Nils), Halling, R. E. (Roy E.), Hansen, K. (Karen), Harder, C. B. (Christoffer Bugge), Heilmann-Clausen, J. (Jacob), Helleman, S. (Stip), Henriot, A. (Alain), Hernandez-Restrepo, M. (Margarita), Herve, R. (Raphael), Hobart, C. (Caroline), Hoffmeister, M. (Mascha), Hoiland, K. (Klaus), Holec, J. (Jan), Holien, H. (Hakon), Hughes, K. (Karen), Hubka, V. (Vit), Huhtinen, S. (Seppo), Ivancevic, B. (Boris), Jagers, M. (Marian), Jaklitsch, W. (Walter), Jansen, A. (AnnaElise), Jayawardena, R. S. (Ruvishika S.), Jeppesen, T. S. (Thomas Stjernegaard), Jeppson, M. (Mikael), Johnston, P. (Peter), Jorgensen, P. M. (Per Magnus), Karnefelt, I. (Ingvar), Kalinina, L. B. (Liudmila B.), Kantvilas, G. (Gintaras), Karadelev, M. (Mitko), Kasuya, T. (Taiga), Kautmanova, I. (Ivona), Kerrigan, R. W. (Richard W.), Kirchmair, M. (Martin), Kiyashko, A. (Anna), Knapp, D. G. (Daniel G.), Knudsen, H. (Henning), Knudsen, K. (Kerry), Knutsson, T. (Tommy), Kolarik, M. (Miroslav), Koljalg, U. (Urmas), Kosuthova, A. (Alica), Koszka, A. (Attila), Kotiranta, H. (Heikki), Kotkova, V. (Vera), Koukol, O. (Ondrej), Kout, J. (Jiri), Kovacs, G. M. (Gabor M.), Kriz, M. (Martin), Kruys, A. (Asa), Kudera, V. (Viktor), Kudzma, L. (Linas), Kuhar, F. (Francisco), Kukwa, M. (Martin), Kumar, T. K. (T. K. Arun), Kunca, V. (Vladimir), Kusan, I. (Ivana), Kuyper, T. W. (Thomas W.), Lado, C. (Carlos), Laessoe, T. (Thomas), Laine, P. (Patrice), Langer, E. (Ewald), Larsson, E. (Ellen), Larsson, K.-H. (Karl-Henrik), Laursen, G. (Gary), Lechat, C. (Christian), Lee, S. (Serena), Lendemer, J. C. (James C.), Levin, L. (Laura), Lindemann, U. (Uwe), Lindstrom, H. (Hakan), Liu, X. (Xingzhong), Hernandez, R. C. (Regulo Carlos Llarena), Llop, E. (Esteve), Locsmandi, C. (Csaba), Lodge, D. J. (Deborah Jean), Loizides, M. (Michael), Lokos, L. (Laszlo), Luangsa-ard, J. (Jennifer), Luderitz, M. (Matthias), Lumbsch, T. (Thorsten), Lutz, M. (Matthias), Mahoney, D. (Dan), Malysheva, E. (Ekaterina), Malysheva, V. (Vera), Manimohan, P. (Patinjareveettil), Mann-Felix, Y. (Yasmina), Marques, G. (Guilhermina), Martinez-Gil, R. (Ruben), Marson, G. (Guy), Mata, G. (Gerardo), Matheny, P. B. (P. Brandon), Mathiassen, G. H. (Geir Harald), Matocec, N. (Neven), Mayrhofer, H. (Helmut), Mehrabi, M. (Mehdi), Melo, I. (Ireneia), Mesic, A. (Armin), Methven, A. S. (Andrew S.), Miettinen, O. (Otto), Romero, A. M. (Ana M. Millanes), Miller, A. N. (Andrew N.), Mitchell, J. K. (James K.), Moberg, R. (Roland), Moreau, P.-A. (Pierre-Arthur), Moreno, G. (Gabriel), Morozova, O. (Olga), Morte, A. (Asuncion), Muggia, L. (Lucia), Gonzalez, G. M. (Guillermo Munoz), Myllys, L. (Leena), Nagy, I. (Istvan), Nagy, L. G. (Laszlo G.), Neves, M. A. (Maria Alice), Niemela, T. (Tuomo), Nimis, P. L. (Pier Luigi), Niveiro, N. (Nicolas), Noordeloos, M. E. (Machiel E.), Nordin, A. (Anders), Noumeur, S. R. (Sara Raouia), Novozhilov, Y. (Yuri), Nuytinck, J. (Jorinde), Ohenoja, E. (Esteri), Fiuza, P. O. (Patricia Oliveira), Orange, A. (Alan), Ordynets, A. (Alexander), Ortiz-Santana, B. (Beatriz), Pacheco, L. (Leticia), Pal-Fam, F. (Ferenc), Palacio, M. (Melissa), Palice, Z. (Zdenek), Papp, V. (Viktor), Partel, K. (Kadri), Pawlowska, J. (Julia), Paz, A. (Aurelia), Peintner, U. (Ursula), Pennycook, S. (Shaun), Pereira, O. L. (Olinto Liparini), Daniels, P. P. (Pablo Perez), Capella, M. A. (Miguel A. Perez-De-Gregorio), del Amo, C. M. (Carlos Manuel Perez), Gorjon, S. P. (Sergio Perez), Perez-Ortega, S. (Sergio), Perez-Vargas, I. (Israel), Perry, B. A. (Brian A.), Petersen, J. H. (Jens H.), Petersen, R. H. (Ronald H.), Pfister, D. H. (Donald H.), Phukhamsakda, C. (Chayanard), Piatek, M. (Marcin), Piepenbring, M. (Meike), Pino-Bodas, R. (Raquel), Esquivel, J. P. (Juan Pablo Pinzon), Pirot, P. (Paul), Popov, E. S. (Eugene S.), Popoff, O. (Orlando), Alvaro, M. P. (Maria Prieto), Printzen, C. (Christian), Psurtseva, N. (Nadezhda), Purahong, W. (Witoon), Quijada, L. (Luis), Rambold, G. (Gerhard), Ramirez, N. A. (Natalia A.), Raja, H. (Huzefa), Raspe, O. (Olivier), Raymundo, T. (Tania), Reblova, M. (Martina), Rebriev, Y. A. (Yury A.), Garcia, J. d. (Juan de Dios Reyes), Ripoll, M. A. (Miguel Angel Ribes), Richard, F. (Franck), Richardson, M. J. (Mike J.), Rico, V. J. (Victor J.), Robledo, G. L. (Gerardo Lucio), Barbosa, F. R. (Flavia Rodrigues), Rodriguez-Caycedo, C. (Cristina), Rodriguez-Flakus, P. (Pamela), Ronikier, A. (Anna), Casas, L. R. (Luis Rubio), Rusevska, K. (Katerina), Saar, G. (Gunter), Saar, I. (Irja), Salcedo, I. (Isabel), Martinez, S. M. (Sergio M. Salcedo), Montoya, C. A. (Carlos A. Salvador), Sanchez-Ramirez, S. (Santiago), Sandoval-Sierra, J. V. (J. Vladimir), Santamaria, S. (Sergi), Monteiro, J. S. (Josiane Santana), Schroers, H. J. (Hans Josef), Schulz, B. (Barbara), Schmidt-Stohn, G. (Geert), Schumacher, T. (Trond), Senn-Irlet, B. (Beatrice), Sevcikova, H. (Hana), Shchepin, O. (Oleg), Shirouzu, T. (Takashi), Shiryaev, A. (Anton), Siepe, K. (Klaus), Sir, E. B. (Esteban B.), Sohrabi, M. (Mohammad), Soop, K. (Karl), Spirin, V. (Viacheslav), Spribille, T. (Toby), Stadler, M. (Marc), Stalpers, J. (Joost), Stenroos, S. (Soili), Suija, A. (Ave), Sunhede, S. (Stellan), Svantesson, S. (Sten), Svensson, S. (Sigvard), Svetasheva, T. Y. (Tatyana Yu), Swierkosz, K. (Krzysztof), Tamm, H. (Heidi), Taskin, H. (Hatira), Taudiere, A. (Adrien), Tedebrand, J.-O. (Jan-Olof), Lahoz, R. T. (Raul Tena), Temina, M. (Marina), Thell, A. (Arne), Thines, M. (Marco), Thor, G. (Goren), Thus, H. (Holger), Tibell, L. (Leif), Tibell, S. (Sanja), Timdal, E. (Einar), Tkalcec, Z. (Zdenko), Tonsberg, T. (Tor), Trichies, G. (Gerard), Triebel, D. (Dagmar), Tsurykau, A. (Andrei), Tulloss, R. E. (Rodham E.), Tuovinen, V. (Veera), Sosa, M. U. (Miguel Ulloa), Urcelay, C. (Carlos), Valade, F. (Francois), Garza, R. V. (Ricardo Valenzuela), van den Boom, P. (Pieter), Van Vooren, N. (Nicolas), Vasco-Palacios, A. M. (Aida M.), Vauras, J. (Jukka), Santos, J. M. (Juan Manuel Velasco), Vellinga, E. (Else), Verbeken, A. (Annemieke), Vetlesen, P. (Per), Vizzini, A. (Alfredo), Voglmayr, H. (Hermann), Volobuev, S. (Sergey), von Brackel, W. (Wolfgang), Voronina, E. (Elena), Walther, G. (Grit), Watling, R. (Roy), Weber, E. (Evi), Wedin, M. (Mats), Weholt, O. (Oyvind), Westberg, M. (Martin), Yurchenko, E. (Eugene), Zehnalek, P. (Petr), Zhang, H. (Huang), Zhurbenko, M. P. (Mikhail P.), and Ekmani, S. (Stefan)

Abstract

Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN., Publisher’s Note A first version of this text was prepared by the first eight authors and the last one, given here. The other listed co-authors in the article PDF support the content, and their actual contributions varied from only support to additions that substantially improved the content. The full details of all co-authors, with their affiliations, are included in Supplementary Table 1 after p.175 of the article for reasons of clarity and space. Slavomír Adamčík Institute of Botany, Plant Science and Biodiversity Centre, Slovak Academy of Sciences, Dúbravská cesta 9, 845 23 Bratislava, Slovakia Teuvo Ahti Finnish Museum of Natural History, P.O. Box 7, 00014 University of Helsinki, Finland M. Catherine Aime Purdue University, 915 W. State St., West Lafayette, Indiana 47907, U.S.A. A. Martyn Ainsworth Royal Botanic Gardens, Kew, Richmond, Surrey, TW9 3AB, United Kingdom László Albert Hungarian Mycological Society, 1087 Könyves Kálmán krt. 40, Budapest, Hungary Edgardo Albertó Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús, Universidad Nacional de San Martin-Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina Alberto Altés García Facultad de Biología, Ciencias Ambientales y Química, Universidad de Alcalá, 28805 Alcalá de Henares, Madrid, Spain Dmitry Ageev SIGNATEC Ltd., 630090, Novosibirsk, Akademgorodok (Novosibirsk Scientific Center), Inzhenernaya str., 22, Russia Reinhard Agerer Ludwig-Maximilians-Universität München, Menzinger Str. 67, 80638 München, Germany Begona Aguirre-Hudson Royal Botanic Gardens, Kew, Richmond, Surrey, TW9 3AB, United Kingdom Joe Ammirati University of Washington, Seattle, Washington 98195-1800, U.S.A. Harry Andersson Eichhahnweg 29a, 38108 Braunschweig, Germany Claudio Angelini Jardín Botánico Nacional Dr. Rafael Ma. Moscoso, Apartado 21-9, Santo Domingo, Dominican Republic Vladimír Antonín Moravian Museum, Zeny trh 6, 659 37 Brno, Czech Republic Takayuki Aoki Genetic Reso

Published
2018

7. Considerations and consequences of allowing DNA sequence data as types of fungal taxa

Author

Universitat Rovira i Virgili, Zamora J; Svensson M; Kirschner R; Olariaga I; Ryman S; Parra L; Geml J; Rosling A; Adam?ík S; Ahti T; Aime M; Ainsworth A; Albert L; Albertó E; Garcia A; Ageev D; Agerer R; Aguirre-Hudson B; Ammirati J; Andersson H; Angelini C; Antonín V; Aoki T; Aptroot A; Argaud D; Sosa B; Aronsen A; Arup U; Asgari B; Assyov B; Atienza V; Bandini D; Baptista-Ferreira J; Baral H; Baroni T; Barreto R; Beker H; Bell A; Bellanger J; Bellù F, Universitat Rovira i Virgili, and Zamora J; Svensson M; Kirschner R; Olariaga I; Ryman S; Parra L; Geml J; Rosling A; Adam?ík S; Ahti T; Aime M; Ainsworth A; Albert L; Albertó E; Garcia A; Ageev D; Agerer R; Aguirre-Hudson B; Ammirati J; Andersson H; Angelini C; Antonín V; Aoki T; Aptroot A; Argaud D; Sosa B; Aronsen A; Arup U; Asgari B; Assyov B; Atienza V; Bandini D; Baptista-Ferreira J; Baral H; Baroni T; Barreto R; Beker H; Bell A; Bellanger J; Bellù F

Abstract

© 2018 International Mycological Association. Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not re

Published
2018

15. Stimulation of glucose-6-phosphatase gene expression by glucose and fructose-2,6-bisphosphate.

Author

Argaud, D, Kirby, T L, Newgard, C B, and Lange, A J

Abstract

Glucose-6-phosphatase, a key enzyme in the homeostatic regulation of blood glucose concentration, catalyzes the terminal step in gluconeogenesis and glycogenolysis. Glucose, the product of the glucose-6-phosphatase reaction, dramatically increases the level of glucose-6-phosphatase mRNA transcripts in primary hepatocytes (20-fold), and the maximum response is obtained at a glucose concentration as low as 11 mM. Glucose specifically increases glucose-6-phosphatase mRNA and L-type pyruvate kinase mRNA. In the rat hepatoma-derived cell line, Fao, glucose increases the glucose-6-phosphatase mRNA only modestly (3-fold). In the presence of high glucose concentrations, overexpression of glucokinase in Fao cells via recombinant adenovirus vectors increases lactate production to the level found in primary hepatocytes and increases glucose-6-phosphatase gene expression by 21-fold. Similar overexpression of hexokinase I in Fao cells with high levels of glucose does not increase lactate production nor does it change the response of glucose-6-phosphatase mRNA to glucose. Glucokinase overexpression in Fao cells blunts the previously reported inhibitory effect of insulin on glucose-6-phosphatase gene expression in these cells. Raising the cellular concentration of fructose-2,6-bisphosphate, a potent effector of the direction of carbon flux through the gluconeogenic and glycolytic pathways, also stimulated glucose-6-phosphatase gene expression in Fao cells. Increasing the fructose-2,6-bisphosphate concentration over a 15-fold range (12 +/- 1 to 187 +/- 17 pmol/plate) via an adenoviral vector overexpression system, led to a 6-fold increase (0.32 +/- 0. 03 to 2.2 +/- 0.33 arbitrary units of mRNA) in glucose-6-phosphatase gene expression with a concomitant increase in glycolysis and a decrease in gluconeogenesis. Also, the effects of fructose-2, 6-bisphosphate concentrations on fructose-1,6-bisphosphatase gene expression were stimulatory, leading to a 5-6-fold increase in mRNA level over a 15-fold range in fructose-2,6-bisphosphate level. Liver pyruvate kinase and phosphoenolpyruvate carboxykinase mRNA were unchanged by the manipulation of fructose-2,6-bisphosphate level.

Published
1997

16. Adenovirus-mediated overexpression of liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase in gluconeogenic rat hepatoma cells. Paradoxical effect on Fru-2,6-P2 levels.

Author

Argaud, D, Lange, A J, Becker, T C, Okar, D A, el-Maghrabi, M R, Newgard, C B, and Pilkis, S J

Abstract

6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase has been postulated to be a metabolic signaling enzyme, which acts as a switch between glycolysis and gluconeogenesis in mammalian liver by regulating the level of fructose 2,6-bisphosphate. The effect of overexpressing the bifunctional enzyme was studied in FAO cells transduced with recombinant adenoviral constructs of either the wild-type enzyme or a double mutant that has no bisphosphatase activity or protein kinase phosphorylation site. With both constructs, the mRNA and protein were overexpressed by 150- and 40-fold, respectively. Addition of cAMP to cells overexpressing the wild-type enzyme increased the S0.5 for fructose 6-phosphate of the kinase by 1.5-fold but had no effect on the overexpressed double mutant. When the wild-type enzyme was overexpressed, there was a decrease in fructose 2,6-bisphosphate levels, even though 6-phosphofructo-2-kinase maximal activity increased more than 22-fold and was in excess of fructose-2,6-bisphosphatase maximal activity. The kinase:bisphosphatase maximal activity ratio was decreased, indicating that the overexpressed enzyme was phosphorylated by cAMP-dependent protein kinase. Overexpression of the double mutant resulted in a 28-fold increase in kinase maximal activity and a 3-4-fold increase in fructose 2,6-bisphosphate levels. Overexpression of this form inhibited the rate of glucose production from dihydroxyacetone by 90% and stimulated the rate of lactate plus pyruvate production by 200%. In contrast, overexpression of the wild-type enzyme enhanced glucose production and inhibited lactate plus pyruvate production. These results provide direct support for fructose 2,6-bisphosphate as a regulator of gluconeogenic/glycolytic pathway flux and suggest that regulation of bifunctional enzyme activities by covalent modification is more important than the amount of the protein.

Published
1995

17. Integrative genomic analyses identify candidate causal genes for calcific aortic valve stenosis involving tissue-specific regulation.

Author

Thériault S, Li Z, Abner E, Luan J, Manikpurage HD, Houessou U, Zamani P, Briend M, Boudreau DK, Gaudreault N, Frenette L, Argaud D, Dahmene M, Dagenais F, Clavel MA, Pibarot P, Arsenault BJ, Boekholdt SM, Wareham NJ, Esko T, Mathieu P, and Bossé Y

Subjects
Humans, Genome-Wide Association Study, Genomics, Aortic Valve metabolism, Aortic Valve pathology, Aortic Valve Stenosis genetics, Calcinosis
Abstract

There is currently no medical therapy to prevent calcific aortic valve stenosis (CAVS). Multi-omics approaches could lead to the identification of novel molecular targets. Here, we perform a genome-wide association study (GWAS) meta-analysis including 14,819 cases among 941,863 participants of European ancestry. We report 32 genomic loci, among which 20 are novel. RNA sequencing of 500 human aortic valves highlights an enrichment in expression regulation at these loci and prioritizes candidate causal genes. Homozygous genotype for a risk variant near TWIST1, a gene involved in endothelial-mesenchymal transition, has a profound impact on aortic valve transcriptomics. We identify five genes outside of GWAS loci by combining a transcriptome-wide association study, colocalization, and Mendelian randomization analyses. Using cross-phenotype and phenome-wide approaches, we highlight the role of circulating lipoproteins, blood pressure and inflammation in the disease process. Our findings pave the way for the development of novel therapies for CAVS., (© 2024. The Author(s).)

Published
2024
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18. Enhancer promoter interactome and Mendelian randomization identify network of druggable vascular genes in coronary artery disease.

Author

Chignon A, Mathieu S, Rufiange A, Argaud D, Voisine P, Bossé Y, Arsenault BJ, Thériault S, and Mathieu P

Subjects
Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide genetics, Quantitative Trait Loci genetics, Coronary Artery Disease genetics
Abstract

Coronary artery disease (CAD) is a multifactorial disorder, which is partly heritable. Herein, we implemented a mapping of CAD-associated candidate genes by using genome-wide enhancer-promoter conformation (H3K27ac-HiChIP) and expression quantitative trait loci (eQTL). Enhancer-promoter anchor loops from human coronary artery smooth muscle cells (HCASMC) explained 22% of the heritability for CAD. 3D enhancer-promoter genome mapping of CAD-genes in HCASMC was enriched in vascular eQTL genes. By using colocalization and Mendelian randomization analyses, we identified 58 causal candidate vascular genes including some druggable targets (MAP3K11, CAMK1D, PDGFD, IPO9 and CETP). A network analysis of causal candidate genes was enriched in TGF beta and MAPK pathways. The pharmacologic inhibition of causal candidate gene MAP3K11 in vascular SMC reduced the expression of athero-relevant genes and lowered cell migration, a cardinal process in CAD. Genes connected to enhancers are enriched in vascular eQTL and druggable genes causally associated with CAD., (© 2022. The Author(s).)

Published
2022
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19. Genome-wide chromatin contacts of super-enhancer-associated lncRNA identify LINC01013 as a regulator of fibrosis in the aortic valve.

Author

Chignon A, Argaud D, Boulanger MC, Mkannez G, Bon-Baret V, Li Z, Thériault S, Bossé Y, and Mathieu P

Subjects
Aged, Aortic Valve metabolism, Aortic Valve Stenosis metabolism, Calcinosis metabolism, Chromatin Immunoprecipitation Sequencing, Enhancer Elements, Genetic, Female, Humans, Male, Middle Aged, Promoter Regions, Genetic, Signal Transduction, Transforming Growth Factor beta1 metabolism, Up-Regulation, Aortic Valve pathology, Aortic Valve Stenosis genetics, Calcinosis genetics, Chromatin metabolism, Connective Tissue Growth Factor genetics, RNA, Long Noncoding genetics, Transcription Factors genetics
Abstract

Calcific aortic valve disease (CAVD) is characterized by a fibrocalcific process. The regulatory mechanisms that drive the fibrotic response in the aortic valve (AV) are poorly understood. Long noncoding RNAs derived from super-enhancers (lncRNA-SE) control gene expression and cell fate. Herein, multidimensional profiling including chromatin immunoprecipitation and sequencing, transposase-accessible chromatin sequencing, genome-wide 3D chromatin contacts of enhancer-promoter identified LINC01013 as an overexpressed lncRNA-SE during CAVD. LINC01013 is within a loop anchor, which has contact with the promoter of CCN2 (CTGF) located at ~180 kb upstream. Investigation showed that LINC01013 acts as a decoy factor for the negative transcription elongation factor E (NELF-E), whereby it controls the expression of CCN2. LINC01013-CCN2 is part of a transforming growth factor beta 1 (TGFB1) network and exerts a control over fibrogenesis. These findings illustrate a novel mechanism whereby a dysregulated lncRNA-SE controls, through a looping process, the expression of CCN2 and fibrogenesis of the AV., Competing Interests: The authors have declared that no competing interests exist.

Published
2022
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20. System Genetics Including Causal Inference Identify Immune Targets for Coronary Artery Disease and the Lifespan.

Author

Bon-Baret V, Chignon A, Boulanger MC, Li Z, Argaud D, Arsenault BJ, Thériault S, Bossé Y, and Mathieu P

Subjects
Antibodies immunology, Coronary Artery Disease pathology, Genome-Wide Association Study, Glutathione Peroxidase genetics, Humans, Ligands, Macrophages cytology, Macrophages metabolism, Mendelian Randomization Analysis, Odds Ratio, Protein Interaction Maps genetics, Quantitative Trait Loci, Receptors, CCR5 chemistry, Receptors, CCR5 immunology, Receptors, CCR5 metabolism, Risk Factors, Single-Cell Analysis, Small Molecule Libraries chemistry, Small Molecule Libraries metabolism, Vascular Endothelial Growth Factor Receptor-1 chemistry, Vascular Endothelial Growth Factor Receptor-1 immunology, Vascular Endothelial Growth Factor Receptor-1 metabolism, Glutathione Peroxidase GPX1, Coronary Artery Disease genetics, Longevity
Abstract

Background: Randomized clinical trials indicate that the immune response plays a significant role in coronary artery disease (CAD), a disorder impacting the lifespan potential. However, the identification of targets critical to the immune response in atheroma is still hampered by a lack of solid inference., Methods: Herein, we implemented a system genetics approach to identify causally associated immune targets implicated in atheroma. We leveraged genome-wide association studies to perform mapping and Mendelian randomization to assess causal associations between gene expression in blood cells with CAD and the lifespan. Expressed genes (eGenes) were prioritized in network and in single-cell expression derived from plaque immune cells., Results: Among 840 CAD-associated blood eGenes, 37 were predicted causally associated with CAD and 6 were also associated with the parental lifespan in Mendelian randomization. In multivariable Mendelian randomization, the impact of eGenes on the lifespan potential was mediated by the CAD risk. Predicted causal eGenes were central in network. FLT1 and CCR5 were identified as targets of approved drugs, whereas 22 eGenes were deemed tractable for the development of small molecules and antibodies. Analyses of plaque immune single-cell expression identified predicted causal eGenes enriched in macrophages ( GPX1 , C4orf3 ) and involved in ligand-receptor interactions ( CCR5 )., Conclusions: We identified 37 blood eGenes predicted causally associated with CAD. The predicted expression for 6 eGenes impacted the lifespan potential through the risk of CAD. Prioritization based on network, annotations, and single-cell expression identified targets deemed tractable for the development of drugs and for drug repurposing.

Published
2021
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21. Enhancer-associated aortic valve stenosis risk locus 1p21.2 alters NFATC2 binding site and promotes fibrogenesis.

Author

Chignon A, Rosa M, Boulanger MC, Argaud D, Devillers R, Bon-Baret V, Mkannez G, Li Z, Rufiange A, Gaudreault N, Gosselin D, Thériault S, Bossé Y, and Mathieu P

Abstract

Genome-wide association studies for calcific aortic valve stenosis (CAVS) previously reported strong signal for noncoding variants at 1p21.2. Previous study using Mendelian randomization suggested that the locus controls the expression of PALMD encoding Palmdelphin (PALMD). However, the molecular regulation at the locus and the impact of PALMD on the biology of the aortic valve is presently unknown. 3D genetic mapping and CRISPR activation identified rs6702619 as being located in a distant-acting enhancer, which controls the expression of PALMD . DNA-binding assay showed that the risk variant modified the DNA shape, which prevented the recruitment of NFATC2 and lowered the expression of PALMD . In co-expression network analysis, a module encompassing PALMD was enriched in actin-based process. Mass spectrometry and functional assessment showed that PALMD is a regulator of actin polymerization. In turn, lower level of PALMD promoted the activation of myocardin-related transcription factor and fibrosis, a key pathobiological process underpinning CAVS., Competing Interests: None., (© 2021 The Author(s).)

Published
2021
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22. Single-cell expression and Mendelian randomization analyses identify blood genes associated with lifespan and chronic diseases.

Author

Chignon A, Bon-Baret V, Boulanger MC, Li Z, Argaud D, Bossé Y, Thériault S, Arsenault BJ, and Mathieu P

Subjects
Aged, Aged, 80 and over, Chronic Disease, Female, Humans, Male, Middle Aged, Blood, Genes, Longevity genetics, Mendelian Randomization Analysis, Single-Cell Analysis
Abstract

The human lifespan is a heritable trait, which is intricately linked to the development of disorders. Here, we show that genetic associations for the parental lifespan are enriched in open chromatin of blood cells. By using blood expression quantitative trait loci (eQTL) derived from 31,684 samples, we identified for the lifespan 125 cis- and 559 trans-regulated expressed genes (eGenes) enriched in adaptive and innate responses. Analysis of blood single-cell expression data showed that eGenes were enriched in dendritic cells (DCs) and the modelling of cell ligand-receptor interactions predicted crosstalk between DCs and a cluster of monocytes with a signature of cytotoxicity. In two-sample Mendelian randomization (MR), we identified 16 blood cis-eGenes causally associated with the lifespan. In MR, the majority of cis-eGene-disorder association pairs had concordant effects with the lifespan. The present work underlined that the lifespan is linked with the immune response and identifies eGenes associated with the lifespan and disorders.

Published
2020
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23. Enhancer-mediated enrichment of interacting JMJD3-DDX21 to ENPP2 locus prevents R-loop formation and promotes transcription.

Author

Argaud D, Boulanger MC, Chignon A, Mkannez G, and Mathieu P

Subjects
CRISPR-Cas Systems, DEAD-box RNA Helicases metabolism, DNA chemistry, DNA metabolism, Enhancer Elements, Genetic, Gene Editing methods, Gene Expression Regulation, HEK293 Cells, Histone Demethylases genetics, Histone Demethylases metabolism, Histones genetics, Histones metabolism, Humans, Inflammation, Jumonji Domain-Containing Histone Demethylases metabolism, Lipopolysaccharides pharmacology, Models, Biological, NF-kappa B genetics, NF-kappa B metabolism, Nucleic Acid Conformation, Phosphoric Diester Hydrolases metabolism, Protein Binding, RNA, Messenger biosynthesis, RNA, Messenger chemistry, Signal Transduction, Transcription Initiation Site, DEAD-box RNA Helicases genetics, DNA genetics, Jumonji Domain-Containing Histone Demethylases genetics, Phosphoric Diester Hydrolases genetics, RNA, Messenger genetics, Transcription, Genetic drug effects
Abstract

ENPP2, which encodes for the enzyme autotaxin (ATX), is overexpressed during chronic inflammatory diseases and various cancers. However, the molecular mechanism involved in the ENPP2 transcription remains elusive. Here, in HEK 293T cells, we demonstrated that lipopolysaccharide (LPS) increased the transcription process at ENPP2 locus through a NF-кB pathway and a reduction of H3K27me3 level, a histone repressive mark, by the demethylase UTX. Simultaneously, the H3K27me3 demethylase JMJD3/KDM6B was recruited to the transcription start site (TSS), within the gene body and controlled the expression of ENPP2 in a non-enzymatic manner. Mass spectrometry data revealed a novel interaction for JMJD3 with DDX21, a RNA helicase that unwinds R-loops created by nascent transcript and DNA template. Upon LPS treatment, JMJD3 is necessary for DDX21 recruitment at ENPP2 locus allowing the resolution of aberrant R-loops. CRISPR-Cas9-mediated deletion of a distant-acting enhancer decreased the expression of ENPP2 and lowered the recruitment of JMJD3-DDX21 complex at TSS and its progression through the gene body. Taken together, these findings revealed that enhancer-mediated enrichment of novel JMJD3-DDX21 interaction at ENPP2 locus is necessary for nascent transcript synthesis via the resolution of aberrant R-loops formation in response to inflammatory stimulus., (© The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Published
2019
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24. DNA methylation of a PLPP3 MIR transposon-based enhancer promotes an osteogenic programme in calcific aortic valve disease.

Author

Mkannez G, Gagné-Ouellet V, Jalloul Nsaibia M, Boulanger MC, Rosa M, Argaud D, Hadji F, Gaudreault N, Rhéaume G, Bouchard L, Bossé Y, and Mathieu P

Subjects
5-Methylcytosine metabolism, Aged, Aortic Valve Stenosis enzymology, Aortic Valve Stenosis pathology, CRISPR-Cas Systems, Calcinosis enzymology, Calcinosis pathology, Calcium metabolism, Case-Control Studies, Down-Regulation, Gene Editing methods, Gene Expression Profiling methods, HEK293 Cells, Humans, Lysophospholipids metabolism, Male, Middle Aged, Phosphatidate Phosphatase metabolism, Aortic Valve enzymology, Aortic Valve pathology, Aortic Valve Stenosis genetics, Calcinosis genetics, DNA Methylation, DNA Transposable Elements, Osteogenesis genetics, Phosphatidate Phosphatase genetics, Promoter Regions, Genetic
Abstract

Aims: Calcific aortic valve disease (CAVD) is characterized by the osteogenic transition of valve interstitial cells (VICs). In CAVD, lysophosphatidic acid (LysoPA), a lipid mediator with potent osteogenic activity, is produced in the aortic valve (AV) and is degraded by membrane-associated phospholipid phosphatases (PLPPs). We thus hypothesized that a dysregulation of PLPPs could participate to the osteogenic reprograming of VICs during CAVD., Methods and Results: The expression of PLPPs was examined in human control and mineralized AVs and comprehensive analyses were performed to document the gene regulation and impact of PLPPs on the osteogenic transition of VICs. We found that PLPP3 gene and enzymatic activity were downregulated in mineralized AVs. Multidimensional gene profiling in 21 human AVs showed that expression of PLPP3 was inversely correlated with the level of 5-methylcytosine (5meC) located in an intronic mammalian interspersed repeat (MIR) element. Bisulphite pyrosequencing in a larger series of 67 AVs confirmed that 5meC in intron 1 was increased by 2.2-fold in CAVD compared with control AVs. In isolated cells, epigenome editing with clustered regularly interspersed short palindromic repeats-Cas9 system containing a deficient Cas9 fused with DNA methyltransferase (dCas9-DNMT) was used to increase 5meC in the intronic enhancer and showed that it reduced significantly the expression of PLPP3. Knockdown experiments showed that lower expression of PLPP3 in VICs promotes an osteogenic programme., Conclusions: DNA methylation of a MIR-based enhancer downregulates the expression of PLPP3 and promotes the mineralization of the AV.

Published
2018
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25. Considerations and consequences of allowing DNA sequence data as types of fungal taxa.

Author

Zamora JC, Svensson M, Kirschner R, Olariaga I, Ryman S, Parra LA, Geml J, Rosling A, Adamčík S, Ahti T, Aime MC, Ainsworth AM, Albert L, Albertó E, García AA, Ageev D, Agerer R, Aguirre-Hudson B, Ammirati J, Andersson H, Angelini C, Antonín V, Aoki T, Aptroot A, Argaud D, Sosa BIA, Aronsen A, Arup U, Asgari B, Assyov B, Atienza V, Bandini D, Baptista-Ferreira JL, Baral HO, Baroni T, Barreto RW, Beker H, Bell A, Bellanger JM, Bellù F, Bemmann M, Bendiksby M, Bendiksen E, Bendiksen K, Benedek L, Bérešová-Guttová A, Berger F, Berndt R, Bernicchia A, Biketova AY, Bizio E, Bjork C, Boekhout T, Boertmann D, Böhning T, Boittin F, Boluda CG, Boomsluiter MW, Borovička J, Brandrud TE, Braun U, Brodo I, Bulyonkova T, Burdsall HH Jr, Buyck B, Burgaz AR, Calatayud V, Callac P, Campo E, Candusso M, Capoen B, Carbó J, Carbone M, Castañeda-Ruiz RF, Castellano MA, Chen J, Clerc P, Consiglio G, Corriol G, Courtecuisse R, Crespo A, Cripps C, Crous PW, da Silva GA, da Silva M, Dam M, Dam N, Dämmrich F, Das K, Davies L, De Crop E, De Kesel A, De Lange R, De Madrignac Bonzi B, Dela Cruz TEE, Delgat L, Demoulin V, Desjardin DE, Diederich P, Dima B, Dios MM, Divakar PK, Douanla-Meli C, Douglas B, Drechsler-Santos ER, Dyer PS, Eberhardt U, Ertz D, Esteve-Raventós F, Salazar JAE, Evenson V, Eyssartier G, Farkas E, Favre A, Fedosova AG, Filippa M, Finy P, Flakus A, Fos S, Fournier J, Fraiture A, Franchi P, Molano AEF, Friebes G, Frisch A, Fryday A, Furci G, Márquez RG, Garbelotto M, García-Martín JM, Otálora MAG, Sánchez DG, Gardiennet A, Garnica S, Benavent IG, Gates G, da Cruz Lima Gerlach A, Ghobad-Nejhad M, Gibertoni TB, Grebenc T, Greilhuber I, Grishkan B, Groenewald JZ, Grube M, Gruhn G, Gueidan C, Gulden G, Gusmão LF, Hafellner J, Hairaud M, Halama M, Hallenberg N, Halling RE, Hansen K, Harder CB, Heilmann-Clausen J, Helleman S, Henriot A, Hernandez-Restrepo M, Herve R, Hobart C, Hoffmeister M, Høiland K, Holec J, Holien H, Hughes K, Hubka V, Huhtinen S, Ivančević B, Jagers M, Jaklitsch W, Jansen A, Jayawardena RS, Jeppesen TS, Jeppson M, Johnston P, Jørgensen PM, Kärnefelt I, Kalinina LB, Kantvilas G, Karadelev M, Kasuya T, Kautmanová I, Kerrigan RW, Kirchmair M, Kiyashko A, Knapp DG, Knudsen H, Knudsen K, Knutsson T, Kolařík M, Kõljalg U, Košuthová A, Koszka A, Kotiranta H, Kotkova V, Koukol O, Kout J, Kovács GM, Kříž M, Kruys Å, Kučera V, Kudzma L, Kuhar F, Kukwa M, Arun Kumar TK, Kunca V, Kušan I, Kuyper TW, Lado C, Læssøe T, Lainé P, Langer E, Larsson E, Larsson KH, Laursen G, Lechat C, Lee S, Lendemer JC, Levin L, Lindemann U, Lindström H, Liu X, Hernandez RCL, Llop E, Locsmándi C, Lodge DJ, Loizides M, Lőkös L, Luangsa-Ard J, Lüderitz M, Lumbsch T, Lutz M, Mahoney D, Malysheva E, Malysheva V, Manimohan P, Marin-Felix Y, Marques G, Martínez-Gil R, Marson G, Mata G, Matheny PB, Mathiassen GH, Matočec N, Mayrhofer H, Mehrabi M, Melo I, Mešić A, Methven AS, Miettinen O, Romero AMM, Miller AN, Mitchell JK, Moberg R, Moreau PA, Moreno G, Morozova O, Morte A, Muggia L, González GM, Myllys L, Nagy I, Nagy LG, Neves MA, Niemelä T, Nimis PL, Niveiro N, Noordeloos ME, Nordin A, Noumeur SR, Novozhilov Y, Nuytinck J, Ohenoja E, Fiuza PO, Orange A, Ordynets A, Ortiz-Santana B, Pacheco L, Pál-Fám F, Palacio M, Palice Z, Papp V, Pärtel K, Pawlowska J, Paz A, Peintner U, Pennycook S, Pereira OL, Daniëls PP, Pérez-De-Gregorio Capella MÀ, Del Amo CMP, Gorjón SP, Pérez-Ortega S, Pérez-Vargas I, Perry BA, Petersen JH, Petersen RH, Pfister DH, Phukhamsakda C, Piątek M, Piepenbring M, Pino-Bodas R, Esquivel JPP, Pirot P, Popov ES, Popoff O, Álvaro MP, Printzen C, Psurtseva N, Purahong W, Quijada L, Rambold G, Ramírez NA, Raja H, Raspé O, Raymundo T, Réblová M, Rebriev YA, de Dios Reyes García J, Ripoll MÁR, Richard F, Richardson MJ, Rico VJ, Robledo GL, Barbosa FR, Rodriguez-Caycedo C, Rodriguez-Flakus P, Ronikier A, Casas LR, Rusevska K, Saar G, Saar I, Salcedo I, Martínez SMS, Montoya CAS, Sánchez-Ramírez S, Sandoval-Sierra JV, Santamaria S, Monteiro JS, Schroers HJ, Schulz B, Schmidt-Stohn G, Schumacher T, Senn-Irlet B, Ševčíková H, Shchepin O, Shirouzu T, Shiryaev A, Siepe K, Sir EB, Sohrabi M, Soop K, Spirin V, Spribille T, Stadler M, Stalpers J, Stenroos S, Suija A, Sunhede S, Svantesson S, Svensson S, Svetasheva TY, Świerkosz K, Tamm H, Taskin H, Taudière A, Tedebrand JO, Lahoz RT, Temina M, Thell A, Thines M, Thor G, Thüs H, Tibell L, Tibell S, Timdal E, Tkalčec Z, Tønsberg T, Trichies G, Triebel D, Tsurykau A, Tulloss RE, Tuovinen V, Sosa MU, Urcelay C, Valade F, Garza RV, van den Boom P, Van Vooren N, Vasco-Palacios AM, Vauras J, Velasco Santos JM, Vellinga E, Verbeken A, Vetlesen P, Vizzini A, Voglmayr H, Volobuev S, von Brackel W, Voronina E, Walther G, Watling R, Weber E, Wedin M, Weholt Ø, Westberg M, Yurchenko E, Zehnálek P, Zhang H, Zhurbenko MP, and Ekman S

Abstract

Nomenclatural type definitions are one of the most important concepts in biological nomenclature. Being physical objects that can be re-studied by other researchers, types permanently link taxonomy (an artificial agreement to classify biological diversity) with nomenclature (an artificial agreement to name biological diversity). Two proposals to amend the International Code of Nomenclature for algae, fungi, and plants (ICN), allowing DNA sequences alone (of any region and extent) to serve as types of taxon names for voucherless fungi (mainly putative taxa from environmental DNA sequences), have been submitted to be voted on at the 11 th International Mycological Congress (Puerto Rico, July 2018). We consider various genetic processes affecting the distribution of alleles among taxa and find that alleles may not consistently and uniquely represent the species within which they are contained. Should the proposals be accepted, the meaning of nomenclatural types would change in a fundamental way from physical objects as sources of data to the data themselves. Such changes are conducive to irreproducible science, the potential typification on artefactual data, and massive creation of names with low information content, ultimately causing nomenclatural instability and unnecessary work for future researchers that would stall future explorations of fungal diversity. We conclude that the acceptance of DNA sequences alone as types of names of taxa, under the terms used in the current proposals, is unnecessary and would not solve the problem of naming putative taxa known only from DNA sequences in a scientifically defensible way. As an alternative, we highlight the use of formulas for naming putative taxa (candidate taxa) that do not require any modification of the ICN.

Published
2018
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26. OxLDL-derived lysophosphatidic acid promotes the progression of aortic valve stenosis through a LPAR1-RhoA-NF-κB pathway.

Author

Nsaibia MJ, Boulanger MC, Bouchareb R, Mkannez G, Le Quang K, Hadji F, Argaud D, Dahou A, Bossé Y, Koschinsky ML, Pibarot P, Arsenault BJ, Marette A, and Mathieu P

Subjects
Animals, Aortic Valve metabolism, Humans, Lysophospholipids pharmacology, Mice, Phosphorylation, Receptors, Lysophosphatidic Acid metabolism, Signal Transduction drug effects, Signal Transduction physiology, Toll-Like Receptor 4 metabolism, Aortic Valve pathology, Aortic Valve Stenosis metabolism, Calcinosis metabolism, Lipoproteins, LDL metabolism, NF-kappa B metabolism, rhoA GTP-Binding Protein metabolism
Abstract

Aims: Oxidatively modified lipoproteins may promote the development/progression of calcific aortic valve stenosis (CAVS). Oxidative transformation of low-density lipoprotein (OxLDL) generates lysophosphatidic acid (LPA), a lipid mediator that accumulates in mineralized aortic valves. LPA activates at least six different G protein-coupled receptors, which may play a role in the pathophysiology of CAVS. We hypothesized that LPA derived from OxLDL may promote a NF-κB signature that drives osteogenesis in the aortic valve., Methods and Results: The role of OxLDL-LPA was examined in isolated valve interstitial cells (VICs) and the molecular pathway was validated in human explanted aortic valves and in a mouse model of CAVS. We found that OxLDL-LPA promoted the mineralization and osteogenic transition of VICs through LPAR1 and the activation of a RhoA-NF-κB pathway. Specifically, we identified that RhoA/ROCK activated IκB kinase alpha, which promoted the phosphorylation of p65 on serine 536 (p65 pS536). p65 pS536 was recruited to the BMP2 promoter and directed an osteogenic program not responsive to the control exerted by the inhibitor of kappa B. In LDLR-/-/ApoB100/100/IGFII transgenic mice (IGFII), which develop CAVS under a high-fat and high-sucrose diet the administration of Ki16425, a Lpar1 blocker, reduced by three-fold the progression rate of CAVS and also decreased the osteogenic activity as measured with a near-infrared fluorescent probe that recognizes hydroxyapatite of calcium., Conclusions: OxLDL-LPA promotes an osteogenic program in the aortic valve through a LPAR1-RhoA/ROCK-p65 pS536 pathway. LPAR1 may represent a suitable target to prevent the progression of CAVS., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.)

Published
2017
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27. Effect of dietary polyunsaturated fatty acids on contractile function of hearts isolated from sedentary and trained rats.

Author

Demaison L, Blet J, Sergiel JP, Gregoire S, and Argaud D

Subjects
Animals, Blood Pressure, Cardiac Output, Dietary Fats, Unsaturated administration & dosage, Fatty Acids analysis, Fatty Acids, Omega-3 pharmacology, Fatty Acids, Omega-6, Fatty Acids, Unsaturated pharmacology, Fish Oils administration & dosage, Fish Oils pharmacology, Heart Rate, Myocardium chemistry, Phospholipids analysis, Physical Conditioning, Animal, Plant Oils administration & dosage, Plant Oils pharmacology, Rats, Sunflower Oil, Dietary Fats, Unsaturated pharmacology, Myocardial Contraction physiology, Physical Exertion
Abstract

Moderate physical training induced a decrease in arterial blood pressure in fish oil-fed rats as compared to sunflower seed oil-fed rats. The purpose of this study was to determine if these changes were due to modifications of the left ventricular function of the heart. Forty rats were fed a semi-purified diet containing either 10% sunflower seed oil or 10% fish oil (EPAX 3000TG, Pronova). Each dietary group was assigned to two sub-groups, one being constituted by sedentary animals and the other by trained animals. Training was achieved by daily running for 60 minutes at moderate intensity for three weeks. At the end of the training period, the animals were sacrificed and their hearts were immediately perfused according to the working mode. The phospholipid fatty acid composition and parameters of the left ventricular function were determined. Feeding fish oil markedly reduced the proportion of n-6 polyunsaturated fatty acids (PUFA, 18:2 n-6, 20:4 n-6, 22:4 n-6 and 22:5 n-6) in cardiac phospholipids. The n-6 PUFA were replaced by n-3 PUFA (mainly docosahexaenoic acid). In sedentary animals, the fluid dynamic (aortic and coronary flow, cardiac output) was not modified by the diet. The heart rate was reduced (-10%) in n-3 PUFA-rich hearts. Physical training did not markedly alter the polyunsaturated fatty acid profile of cardiac phospholipids. Conversely, it reduced the heart rate, aortic flow and cardiac output (-11, -21 and -14%, respectively) at a similar extent in the two dietary groups. In a second set of experiments, the training period was repeated in animals fed a commercially available diet (A103, UAR) which simultaneously provided n-6 and n-3 fatty acids. In these dietary conditions, neither the aortic flow nor the heart rate was decreased by physical exercise. These results suggest that both n-6 and n-3 PUFA in the diet are necessary to ensure a good cardiac adaptation to moderate physical training. Furthermore, the fish oil-induced decrease in arterial blood pressure in trained animals was not related to changes in cardiac contractility, but to a decrease in vascular resistances. Moderate physical training + dietary n-3 PUFA might be used to prevent hypertension and cardiovascular diseases.

Published
2000
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28. The inhibition of phosphoenolpyruvate carboxykinase following in vivo chronic phenobarbital treatment in the rat is due to a post-translational event.

Author

Chauvin C, Brilloit-Petit C, Argaud D, Catelloni F, Velours J, and Leverve XM

Subjects
Animal Nutritional Physiological Phenomena, Animals, Kinetics, Liver chemistry, Liver drug effects, Liver enzymology, Male, Phosphoenolpyruvate Carboxykinase (GTP) metabolism, RNA, Messenger analysis, Rats, Rats, Wistar, Phenobarbital pharmacology, Phosphoenolpyruvate Carboxykinase (GTP) antagonists & inhibitors, Phosphoenolpyruvate Carboxykinase (GTP) genetics, Protein Processing, Post-Translational
Abstract

Chronic treatment of rats with phenobarbital has been reported to decrease gluconeogenesis in rat hepatocytes by a 50% inhibition of phosphoenolpyruvate (P-pyruvate) carboxykinase activity [Argaud, D., Halimi, S., Catelloni, F. & Leverve, X. (1991) Biochem. J. 280, 663-669]. Contrary to the current knowledge of P-pyruvate carboxykinase regulation, we failed to find a diminution of either P-pyruvate carboxykinase protein (by using a polyclonal antibody) or P-pyruvate carboxykinase mRNA, in the liver of rats treated with phenobarbital for 2 weeks. Kinetic studies of P-pyruvate carboxykinase activity, measured by either carboxylation of P-pyruvate or decarboxylation of oxaloacetate, revealed a decrease in both V(max) and Km after phenobarbital treatment, whereas the nutritional state affected only the V(max), as expected. Assessment of P-pyruvate carboxykinase specificity was confirmed by the full inhibition of the enzyme with its specific inhibitor 3-mercaptopicolinate in the micromolar range. P-Pyruvate carboxykinase, purified either by ammonium sulfate fractionation or by immunoprecipitation, exhibited a similar decrease in affinity after phenobarbital treatment. Although the molecular mass does not appear to be altered, the pH sensitivity to 3-mercaptopicolinate inhibition and the enzyme recovery after immunoprecipitation both seemed to be affected. This leads us to propose that the effect of chronic phenobarbital treatment on P-pyruvate carboxykinase activity is not the result of transcriptional regulation but is exerted at the post-translational level.

Published
1996
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29. Metformin decreases gluconeogenesis by enhancing the pyruvate kinase flux in isolated rat hepatocytes.

Author

Argaud D, Roth H, Wiernsperger N, and Leverve XM

Subjects
Adenosine Diphosphate analysis, Adenosine Triphosphate analysis, Animals, Glucagon pharmacology, Lactates metabolism, Lactic Acid, Liver drug effects, Male, Perfusion, Pyruvates metabolism, Pyruvic Acid, Rats, Rats, Wistar, Gluconeogenesis drug effects, Liver enzymology, Metformin pharmacology, Pyruvate Kinase metabolism
Abstract

Metformin (dimethylbiguanide) has been used for more than 30 years as an antihyperglycemic agent in the treatment of diabetes mellitus, but its effect on gluconeogenesis is still controversial. In isolated hepatocytes from fasted rats, a significant inhibition of glucose production from lactate/pyruvate (10:1, mol/mol), fructose, alanine or glutamine, following metformin addition, is observed. Moreover, in hepatocytes perifused with dihydroxyacetone as the gluconeogenic substrate and treated with 0.5 mM metformin, an inhibition of the glucose flux and a simultaneous stimulation of the lactate/pyruvate flux were observed. This enhancement of lactate/pyruvate formation appears to be due to an effect on the pyruvate-kinase enzyme. A direct effect of metformin on pyruvate kinase cannot explain this result, since pyruvate-kinase activity was not affected by metformin at this concentration. In contrast, the addition of metformin caused a significant decrease in the cellular ATP concentration, a known allosteric inhibitor of this enzyme. This could explain the stimulation of pyruvate-kinase activity following metformin addition and thus the inhibition of gluconeogenesis.

Published
1993
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