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1. Immunohistochimie, biologie moléculaire et score clinique pour la détection du syndrome de Muir-Torre à partir d’une tumeur sébacée cutanée

Author

Sinson, H., Karayan-Tapon, L., Godet, J., Rivet, P., Alleyrat, C., Battistella, M., Pierron, H., Morel, F., Lecron, J.C., Favot, L., and Frouin, E.

Abstract

Le diagnostic de tumeur sébacée (TS) soulève toujours la possibilité d’une association avec le syndrome de Muir-Torre (SMT) ce qui permet de dépister des tumeurs malignes profondes (carcinomes colorectaux et endométriaux) avant qu’ils ne deviennent symptomatiques. L’immunohistochimie (IHC), la biologie moléculaire et le score de risque de la Mayo-Clinic sont des approches différentes pour le dépistage du SMT. Nous avons effectué une analyse rétrospective de tumeurs sébacées non sélectionnées afin de déterminer les outils optimaux à mettre en œuvre pour le dépistage du SMT.

Published
2024
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2. Le microenvironnement immun des tumeurs sébacées dépend de l’agressivité des tumeurs mais pas des altérations de la voie de réparation des mésappariements

Author

Frouin, E., Alleyrat, C., Godet, J., Karayan-Tapon, L., Sinson, H., Morel, F., Lecron, J.C., and Favot, L.

Abstract

Le microenvironnement immun des tumeurs sébacés (TSs) a été peu étudié, en particulier dans les lésions bénignes, et n’a jamais été corrélé au statut du système de réparation des mésappariements (MMR).

Published
2024
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5. IL-17A EXACERBATES PSORIASIFORM DERMATITIS IN A MOUSE MODEL OF HIGH-FAT DIET-INDUCED STEATOHEPATITIS

Author

Lecron, J. -C., Vasseur, P., SERRES, L., Jegou, J. -F., Pohin, M., Delwail, A., Petit-Paris, I., Levillain, P., Favot, L., Samson, M., Yssel, H., Morel, F., Silvain, C., Laboratoire Inflammation, Tissus épithéliaux et Cytokines (LITEC), Université de Poitiers, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Unité d'épidémiologie, biostatistique et registre des cancers [Poitou-Charentes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), and Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA)

Subjects
[SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, ComputingMilieux_MISCELLANEOUS
Abstract

International audience; no abstract

Published
2016

6. Martian fluvial conglomerates at gale crater

Author

Williams, R. M. E., Grotzinger, J. P., Dietrich, W. E., Gupta, S., Sumner, D. Y., Wiens, R. C., Mangold, N., Malin, M. C., Edgett, K. S., Maurice, S., Forni, O., Gasnault, O., Ollila, A., Newsom, H. E., Dromart, G., Palucis, M. C., Yingst, R. A., Anderson, R. B., Herkenhoff, K. E., Le Mouelic, S., Goetz, W., Madsen, M. B., Koefoed, A., Jensen, J. K., Bridges, J. C., Schwenzer, S. P., Lewis, K. W., Stack, K. M., Rubin, D., Kah, L. C., Bell, J. F., Farmer, J. D., Sullivan, R., Van Beek, T., Blaney, D. L., Pariser, O., Deen, R. G., Kemppinen, O., Bridges, N., Johnson, J. R., Minitti, M., Cremers, D., Edgar, L., Godber, A., Wadhwa, M., Wellington, D., McEwan, I., Newman, C., Richardson, M., Charpentier, A., Peret, L., King, P., Blank, J., Weigle, G., Schmidt, M., Li, S., Milliken, R., Robertson, K., Sun, V., Baker, M., Edwards, C., Ehlmann, B., Farley, K., Griffes, J., Miller, H., Newcombe, M., Pilorget, C., Rice, M., Siebach, K., Stolper, E., Brunet, C., Hipkin, V., Leveille, R., Marchand, G., Sobron Sanchez, P., Favot, L., Cody, G., Steele, A., Fluckiger, L., Lees, D., Nefian, A., Martin, M., Gailhanou, M., Westall, F., Israel, G., Agard, C., Baroukh, J., Donny, C., Gaboriaud, A., Guillemot, P., Lafaille, V., Lorigny, E., Paillet, A., Perez, R., Saccoccio, M., Yana, C., Aparicio, C. A., Caride Rodriguez, J., Carrasco Blazquez, I., Gomez Gomez, F., Elvira, J. G., Hettrich, S., Lepinette Malvitte, A., Marin Jimenez, M., Frias, J. M., Soler, J. M., Torres, F. J. M., Molina Jurado, A., Sotomayor, L. M., Munoz Caro, G., Navarro Lopez, S., Gonzalez, V. P., Garcia, J. P., Rodriguez Manfredi, J. A., Planello, J. J. R., Alejandra Sans Fuentes, S., Sebastian Martinez, E., Torres Redondo, J., O'Callaghan, R. U., Zorzano Mier, M.-P., Chipera, S., Lacour, J.-L., Mauchien, P., Sirven, J.-B., Manning, H., Fairen, A., Hayes, A., Joseph, J., Squyres, S., Thomas, P., Dupont, A., Lundberg, A., Melikechi, N., Mezzacappa, A., DeMarines, J., Grinspoon, D., Reitz, G., Prats, B., Atlaskin, E., Genzer, M., Harri, A.-M., Haukka, H., Kahanpaa, H., Kauhanen, J., Paton, M., Polkko, J., Schmidt, W., Siili, T., Fabre, C., Wray, J., Wilhelm, M. B., Poitrasson, F., Patel, K., Gorevan, S., Indyk, S., Paulsen, G., Bish, D., Schieber, J., Gondet, B., Langevin, Y., Geffroy, C., Baratoux, D., Berger, G., Cros, A., Uston, C. d., Lasue, J., Lee, Q.-M., Meslin, P.-Y., Pallier, E., Parot, Y., Pinet, P., Schroder, S., Toplis, M., Lewin, E., Brunner, W., Heydari, E., Achilles, C., Oehler, D., Sutter, B., Cabane, M., Coscia, D., Szopa, C., Robert, F., Sautter, V., Nachon, M., Buch, A., Stalport, F., Coll, P., Francois, P., Raulin, F., Teinturier, S., Cameron, J., Clegg, S., Cousin, A., DeLapp, D., Dingler, R., Jackson, R. S., Johnstone, S., Lanza, N., Little, C., Nelson, T., Williams, R. B., Jones, A., Kirkland, L., Treiman, A., Baker, B., Cantor, B., Caplinger, M., Davis, S., Duston, B., Fay, D., Hardgrove, C., Harker, D., Herrera, P., Jensen, E., Kennedy, M. R., Krezoski, G., Krysak, D., Lipkaman, L., McCartney, E., McNair, S., Nixon, B., Posiolova, L., Ravine, M., Salamon, A., Saper, L., Stoiber, K., Supulver, K., Van Beek, J., Zimdar, R., French, K. L., Iagnemma, K., Miller, K., Summons, R., Goesmann, F., Hviid, S., Johnson, M., Lefavor, M., Lyness, E., Breves, E., Dyar, M. D., Fassett, C., Blake, D. F., Bristow, T., DesMarais, D., Edwards, L., Haberle, R., Hoehler, T., Hollingsworth, J., Kahre, M., Keely, L., McKay, C., Bleacher, L., Brinckerhoff, W., Choi, D., Conrad, P., Dworkin, J. P., Eigenbrode, J., Floyd, M., Freissinet, C., Garvin, J., Glavin, D., Harpold, D., Mahaffy, P., Martin, D. K., McAdam, A., Pavlov, A., Raaen, E., Smith, M. D., Stern, J., Tan, F., Trainer, M., Meyer, M., Posner, A., Voytek, M., Anderson, R. C., Aubrey, A., Beegle, L. W., Behar, A., Brinza, D., Calef, F., Christensen, L., Crisp, J. A., DeFlores, L., Feldman, J., Feldman, S., Flesch, G., Hurowitz, J., Jun, I., Keymeulen, D., Maki, J., Mischna, M., Morookian, J. M., Parker, T., Pavri, B., Schoppers, M., Sengstacken, A., Simmonds, J. J., Spanovich, N., de la Torre Juarez, M., Vasavada, A. R., Webster, C. R., Yen, A., Archer, P. D., Cucinotta, F., Jones, J. H., Ming, D., Morris, R. V., Niles, P., Rampe, E., Nolan, T., Fisk, M., Radziemski, L., Barraclough, B., Bender, S., Berman, D., Dobrea, E. N., Tokar, R., Vaniman, D., Leshin, L., Cleghorn, T., Huntress, W., Manhes, G., Hudgins, J., Olson, T., Stewart, N., Sarrazin, P., Grant, J., Vicenzi, E., Wilson, S. A., Bullock, M., Ehresmann, B., Hamilton, V., Hassler, D., Peterson, J., Rafkin, S., Zeitlin, C., Fedosov, F., Golovin, D., Karpushkina, N., Kozyrev, A., Litvak, M., Malakhov, A., Mitrofanov, I., Mokrousov, M., Nikiforov, S., Prokhorov, V., Sanin, A., Tretyakov, V., Varenikov, A., Vostrukhin, A., Kuzmin, R., Clark, B., Wolff, M., McLennan, S., Botta, O., Drake, D., Bean, K., Lemmon, M., Lee, E. M., Sucharski, R., Hernandez, M. A. d. P., Blanco Avalos, J. J., Ramos, M., Kim, M.-H., Malespin, C., Plante, I., Muller, J.-P., Gonzalez, R. N., Ewing, R., Boynton, W., Downs, R., Fitzgibbon, M., Harshman, K., Morrison, S., Kortmann, O., Williams, A., Lugmair, G., Wilson, M. A., Jakosky, B., Zunic, T. B., Frydenvang, J., Kinch, K., Stipp, S. L. S., Boyd, N., Campbell, J. L., Gellert, R., Perrett, G., Pradler, I., VanBommel, S., Jacob, S., Owen, T., Rowland, S., Savijarvi, H., Boehm, E., Bottcher, S., Burmeister, S., Guo, J., Kohler, J., Garcia, C. M., Mellin, R. M., Schweingruber, R. W., McConnochie, T., Benna, M., Franz, H., Bower, H., Brunner, A., Blau, H., Boucher, T., Carmosino, M., Atreya, S., Elliott, H., Halleaux, D., Renno, N., Wong, M., Pepin, R., Elliott, B., Spray, J., Thompson, L., Gordon, S., Williams, J., Vasconcelos, P., Bentz, J., Nealson, K., Popa, R., Moersch, J., Tate, C., Day, M., Kocurek, G., Hallet, B., Sletten, R., Francis, R., McCullough, E., Cloutis, E., ten Kate, I. L., Arvidson, R., Fraeman, A., Scholes, D., Slavney, S., Stein, T., Ward, J., Berger, J., Moores, J. E., NWO-NSO: The role of perchlorates in the preservation of organic compounds on Mars, Petrology, GeoRessources, and Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre de recherches sur la géologie des matières premières minérales et énergétiques (CREGU)-Institut national des sciences de l'Univers (INSU - CNRS)

Subjects
MSL Mars Gale Crater Fluvial Activity, Martian, Multidisciplinary, 010504 meteorology & atmospheric sciences, Outcrop, Curiosity rover, Geochemistry, Mars, Sediment, Fluvial, [SDU.STU]Sciences of the Universe [physics]/Earth Sciences, Mars Exploration Program, 01 natural sciences, Abrasion (geology), martian fluvial conglomerates, 13. Climate action, Rocknest, 0103 physical sciences, MSL, Sedimentary rock, 010303 astronomy & astrophysics, Geology, 0105 earth and related environmental sciences
Abstract

Going to Mars The Mars Science Laboratory spacecraft containing the Curiosity rover, was launched from Earth in November 2011 and arrived at Gale crater on Mars in August 2012. Zeitlin et al. (p. 1080 ) report measurements of the energetic particle radiation environment inside the spacecraft during its cruise to Mars, confirming the hazard likely to be posed by this radiation to astronauts on a future potential trip to Mars. Williams et al. (p. 1068 , see the Perspective by Jerolmack ) report the detection of sedimentary conglomerates (pebbles mixed with sand and turned to rock) at Gale crater. The rounding of the rocks suggests abrasion of the pebbles as they were transported by flowing water several kilometers or more from their source.

Published
2013

7. Abundance and isotopic composition of gases in the martian atmosphere from the Curiosity rover

Author

Mahaffy, P. R., Webster, C. R., Atreya, S. K., Franz, H., Wong, M., Conrad, P. G., Harpold, D., Jones, J. J., Leshin, L. A., Manning, H., Owen, T., Pepin, R. O., Squyres, S., Trainer, M., Kemppinen, O., Bridges, N., Johnson, J. R., Minitti, M., Cremers, D., Bell, J. F., Edgar, L., Farmer, J., Godber, A., Wadhwa, M., Wellington, D., McEwan, I., Newman, C., Richardson, M., Charpentier, A., Peret, L., King, P., Blank, J., Weigle, G., Schmidt, M., Li, S., Milliken, R., Robertson, K., Sun, V., Baker, M., Edwards, C., Ehlmann, B., Farley, K., Griffes, J., Grotzinger, J., Miller, H., Newcombe, M., Pilorget, C., Rice, M., Siebach, K., Stack, K., Stolper, E., Brunet, C., Hipkin, V., Leveille, R., Marchand, G., Sanchez, P. S., Favot, L., Cody, G., Steele, A., Fluckiger, L., Lees, D., Nefian, A., Martin, M., Gailhanou, M., Westall, F., Israel, G., Agard, C., Baroukh, J., Donny, C., Gaboriaud, A., Guillemot, P., Lafaille, V., Lorigny, E., Paillet, A., Perez, R., Saccoccio, M., Yana, C., Armiens-Aparicio, C., Rodriguez, J. C., Blazquez, I. C., Gomez, F. G., Gomez-Elvira, J., Hettrich, S., Malvitte, A. L., Jimenez, M. M., Martinez-Frias, J., Martin-Soler, J., Martin-Torres, F. J., Jurado, A. M., Mora-Sotomayor, L., Caro, G. M., Lopez, S. N., Peinado-Gonzalez, V., Pla-Garcia, J., Manfredi, J. A. R., Romeral-Planello, J. J., Fuentes, S. A. S., Martinez, E. S., Redondo, J. T., Urqui-O'Callaghan, R., Mier, M.-P. Z., Chipera, S., Lacour, J.-L., Mauchien, P., Sirven, J.-B., Fairen, A., Hayes, A., Joseph, J., Sullivan, R., Thomas, P., Dupont, A., Lundberg, A., Melikechi, N., Mezzacappa, A., DeMarines, J., Grinspoon, D., Reitz, G., Prats, B., Atlaskin, E., Genzer, M., Harri, A.-M., Haukka, H., Kahanpaa, H., Kauhanen, J., Paton, M., Polkko, J., Schmidt, W., Siili, T., Fabre, C., Wray, J., Wilhelm, M. B., Poitrasson, F., Patel, K., Gorevan, S., Indyk, S., Paulsen, G., Gupta, S., Bish, D., Schieber, J., Gondet, B., Langevin, Y., Geffroy, C., Baratoux, D., Berger, G., Cros, A., d'Uston, C., Forni, O., Gasnault, O., Lasue, J., Lee, Q.-M., Maurice, S., Meslin, P.-Y., Pallier, E., Parot, Y., Pinet, P., Schroder, S., Toplis, M., Lewin, E., Brunner, W., Heydari, E., Achilles, C., Oehler, D., Sutter, B., Cabane, M., Coscia, D., Szopa, C., Dromart, G., Robert, F., Sautter, V., Le Mouelic, S., Mangold, N., Nachon, M., Buch, A., Stalport, F., Coll, P., Francois, P., Raulin, F., Teinturier, S., Cameron, J., Clegg, S., Cousin, A., DeLapp, D., Dingler, R., Jackson, R. S., Johnstone, S., Lanza, N., Little, C., Nelson, T., Wiens, R. C., Williams, R. B., Jones, A., Kirkland, L., Treiman, A., Baker, B., Cantor, B., Caplinger, M., Davis, S., Duston, B., Edgett, K., Fay, D., Hardgrove, C., Harker, D., Herrera, P., Jensen, E., Kennedy, M. R., Krezoski, G., Krysak, D., Lipkaman, L., Malin, M., McCartney, E., McNair, S., Nixon, B., Posiolova, L., Ravine, M., Salamon, A., Saper, L., Stoiber, K., Supulver, K., Van Beek, J., Van Beek, T., Zimdar, R., French, K. L., Iagnemma, K., Miller, K., Summons, R., Goesmann, F., Goetz, W., Hviid, S., Johnson, M., Lefavor, M., Lyness, E., Breves, E., Dyar, M. D., Fassett, C., Blake, D. F., Bristow, T., DesMarais, D., Edwards, L., Haberle, R., Hoehler, T., Hollingsworth, J., Kahre, M., Keely, L., McKay, C., Bleacher, L., Brinckerhoff, W., Choi, D., Dworkin, J. P., Eigenbrode, J., Floyd, M., Freissinet, C., Garvin, J., Glavin, D., Martin, D. K., McAdam, A., Pavlov, A., Raaen, E., Smith, M. D., Stern, J., Tan, F., Meyer, M., Posner, A., Voytek, M., Anderson, R. C., Aubrey, A., Beegle, L. W., Behar, A., Blaney, D., Brinza, D., Calef, F., Christensen, L., Crisp, J. A., DeFlores, L., Feldman, J., Feldman, S., Flesch, G., Hurowitz, J., Jun, I., Keymeulen, D., Maki, J., Mischna, M., Morookian, J. M., Parker, T., Pavri, B., Schoppers, M., Sengstacken, A., Simmonds, J. J., Spanovich, N., Juarez, M. d. l. T., Vasavada, A. R., Yen, A., Archer, P. D., Cucinotta, F., Ming, D., Morris, R. V., Niles, P., Rampe, E., Nolan, T., Fisk, M., Radziemski, L., Barraclough, B., Bender, S., Berman, D., Dobrea, E. N., Tokar, R., Vaniman, D., Williams, R. M. E., Yingst, A., Lewis, K., Cleghorn, T., Huntress, W., Manhes, G., Hudgins, J., Olson, T., Stewart, N., Sarrazin, P., Grant, J., Vicenzi, E., Wilson, S. A., Bullock, M., Ehresmann, B., Hamilton, V., Hassler, D., Peterson, J., Rafkin, S., Zeitlin, C., Fedosov, F., Golovin, D., Karpushkina, N., Kozyrev, A., Litvak, M., Malakhov, A., Mitrofanov, I., Mokrousov, M., Nikiforov, S., Prokhorov, V., Sanin, A., Tretyakov, V., Varenikov, A., Vostrukhin, A., Kuzmin, R., Clark, B., Wolff, M., McLennan, S., Botta, O., Drake, D., Bean, K., Lemmon, M., Schwenzer, S. P., Anderson, R. B., Herkenhoff, K., Lee, E. M., Sucharski, R., Hernandez, M. A. d. P., Avalos, J. J. B., Ramos, M., Kim, M.-H., Malespin, C., Plante, I., Muller, J.-P., Navarro-Gonzalez, R., Ewing, R., Boynton, W., Downs, R., Fitzgibbon, M., Harshman, K., Morrison, S., Dietrich, W., Kortmann, O., Palucis, M., Sumner, D. Y., Williams, A., Lugmair, G., Wilson, M. A., Rubin, D., Jakosky, B., Balic-Zunic, T., Frydenvang, J., Jensen, J. K., Kinch, K., Koefoed, A., Madsen, M. B., Stipp, S. L. S., Boyd, N., Campbell, J. L., Gellert, R., Perrett, G., Pradler, I., VanBommel, S., Jacob, S., Rowland, S., Savijarvi, H., Boehm, E., Bottcher, S., Burmeister, S., Guo, J., Kohler, J., Garcia, C. M., Mueller-Mellin, R., Wimmer-Schweingruber, R., Bridges, J. C., McConnochie, T., Benna, M., Bower, H., Brunner, A., Blau, H., Boucher, T., Carmosino, M., Elliott, H., Halleaux, D., Renno, N., Elliott, B., Spray, J., Thompson, L., Gordon, S., Newsom, H., Ollila, A., Williams, J., Vasconcelos, P., Bentz, J., Nealson, K., Popa, R., Kah, L. C., Moersch, J., Tate, C., Day, M., Kocurek, G., Hallet, B., Sletten, R., Francis, R., McCullough, E., Cloutis, E., ten Kate, I. L., Arvidson, R., Fraeman, A., Scholes, D., Slavney, S., Stein, T., Ward, J., Berger, J., Moores, J. E., GeoRessources, Institut national des sciences de l'Univers (INSU - CNRS)-Centre de recherches sur la géologie des matières premières minérales et énergétiques (CREGU)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), MSL Science Team, NWO-NSO: The role of perchlorates in the preservation of organic compounds on Mars, and Petrology

Subjects
010504 meteorology & atmospheric sciences, Curiosity rover, chemistry.chemical_element, [SDU.STU]Sciences of the Universe [physics]/Earth Sciences, Mars, MSL Mars Atmosphere Isotopis Composition, martian atmosphere, 01 natural sciences, Astrobiology, Isotopic signature, chemistry.chemical_compound, 0103 physical sciences, MSL, 010303 astronomy & astrophysics, 0105 earth and related environmental sciences, Martian, Multidisciplinary, δ13C, Atmosphere of Mars, Nitrogen, chemistry, 13. Climate action, Sample Analysis at Mars, Carbon dioxide, Environmental science, Carbon monoxide
Abstract

Mars' Atmosphere from Curiosity The Sample Analysis at Mars (SAM) instrument on the Curiosity rover that landed on Mars in August last year is designed to study the chemical and isotopic composition of the martian atmosphere. Mahaffy et al. (p. 263 ) present volume-mixing ratios of Mars' five major atmospheric constituents (CO 2 , Ar, N 2 , O 2 , and CO) and isotope measurements of 40 Ar/ 36 Ar and C and O in CO 2 , based on data from one of SAM's instruments, obtained between 31 August and 21 November 2012. Webster et al. (p. 260 ) used data from another of SAM's instruments obtained around the same period to determine isotope ratios of H, C, and O in atmospheric CO 2 and H 2 O. Agreement between the isotopic ratios measured by SAM with those of martian meteorites, measured in laboratories on Earth, confirms the origin of these meteorites and implies that the current atmospheric reservoirs of CO 2 and H 2 O were largely established after the period of early atmospheric loss some 4 billion years ago.

Published
2013

8. Curiosity at Gale Crater, Mars: Characterization and analysis of the rocknest sand shadow

Author

Blake, D. F., Morris, R. V., Kocurek, G., Morrison, S. M., Downs, R. T., Bish, D., Ming, D. W., Edgett, K. S., Rubin, D., Goetz, W., Madsen, M. B., Sullivan, R., Gellert, R., Campbell, I., Treiman, A. H., McLennan, S. M., Yen, A. S., Grotzinger, J., Vaniman, D. T., Chipera, S. J., Achilles, C. N., Rampe, E. B., Sumner, D., Meslin, P.- Y., Maurice, S., Forni, O., Gasnault, O., Fisk, M., Schmidt, M., Mahaffy, P., Leshin, L. A., Glavin, D., Steele, A., Freissinet, C., Navarro-Gonzalez, R., Yingst, R. A., Kah, L. C., Bridges, N., Lewis, K. W., Bristow, T. F., Farmer, J. D., Crisp, J. A., Stolper, E. M., Des Marais, D. J., Sarrazin, P., Agard, C., Alves Verdasca, J. A., Anderson, R., Archer, D., Armiens-Aparicio, C., Arvidson, R., Atlaskin, E., Atreya, S., Aubrey, A., Baker, B., Baker, M., Balic-Zunic, T., Baratoux, D., Baroukh, J., Barraclough, B., Bean, K., Beegle, L., Behar, A., Bell, J., Bender, S., Benna, M., Bentz, J., Berger, G., Berger, J., Berman, D., Blanco Avalos, J. J., Blaney, D., Blank, J., Blau, H., Bleacher, L., Boehm, E., Botta, O., Bottcher, S., Boucher, T., Bower, H., Boyd, N., Boynton, B., Breves, E., Bridges, J., Brinckerhoff, W., Brinza, D., Brunet, C., Brunner, A., Brunner, W., Buch, A., Bullock, M., Burmeister, S., Cabane, M., Calef, F., Cameron, J., Cantor, B., Caplinger, M., Rodriguez, J. C., Carmosino, M., Blazquez, I. C., Charpentier, A., Choi, D., Clark, B., Clegg, S., Cleghorn, T., Cloutis, E., Cody, G., Coll, P., Conrad, P., Coscia, D., Cousin, A., Cremers, D., Cros, A., Cucinotta, F., d'Uston, C., Davis, S., Day, M., Juarez, M. d. l. T., DeFlores, L., DeLapp, D., DeMarines, J., Dietrich, W., Dingler, R., Donny, C., Drake, D., Dromart, G., Dupont, A., Duston, B., Dworkin, J., Dyar, M. D., Edgar, L., Edwards, C., Edwards, L., Ehlmann, B., Ehresmann, B., Eigenbrode, J., Elliott, B., Elliott, H., Ewing, R., Fabre, C., Fairen, A., Farley, K., Fassett, C., Favot, L., Fay, D., Fedosov, F., Feldman, J., Feldman, S., Fitzgibbon, M., Flesch, G., Floyd, M., Fluckiger, L., Fraeman, A., Francis, R., Francois, P., Franz, H., French, K. L., Frydenvang, J., Gaboriaud, A., Gailhanou, M., Garvin, J., Geffroy, C., Genzer, M., Godber, A., Goesmann, F., Golovin, D., Gomez, F. G., Gomez-Elvira, J., Gondet, B., Gordon, S., Gorevan, S., Grant, J., Griffes, J., Grinspoon, D., Guillemot, P., Guo, J., Gupta, S., Guzewich, S., Haberle, R., Halleaux, D., Hallet, B., Hamilton, V., Hardgrove, C., Harker, D., Harpold, D., Harri, A.-M., Harshman, K., Hassler, D., Haukka, H., Hayes, A., Herkenhoff, K., Herrera, P., Hettrich, S., Heydari, E., Hipkin, V., Hoehler, T., Hollingsworth, J., Hudgins, J., Huntress, W., Hurowitz, J., Hviid, S., Iagnemma, K., Indyk, S., Israel, G., Jackson, R., Jacob, S., Jakosky, B., Jensen, E., Jensen, J. K., Johnson, J., Johnson, M., Johnstone, S., Jones, A., Jones, J., Joseph, J., Jun, I., Kahanpaa, H., Kahre, M., Karpushkina, N., Kasprzak, W., Kauhanen, J., Keely, L., Kemppinen, O., Keymeulen, D., Kim, M.-H., Kinch, K., King, P., Kirkland, L., Koefoed, A., Kohler, J., Kortmann, O., Kozyrev, A., Krezoski, J., Krysak, D., Kuzmin, R., Lacour, J. L., Lafaille, V., Langevin, Y., Lanza, N., Lasue, J., Le Mouelic, S., Lee, E. M., Lee, Q.-M., Lees, D., Lefavor, M., Lemmon, M., Lepinette Malvitte, A., Leveille, R., Lewin-Carpintier, E., Li, S., Lipkaman, L., Little, C., Litvak, M., Lorigny, E., Lugmair, G., Lundberg, A., Lyness, E., Maki, J., Malakhov, A., Malespin, C., Malin, M., Mangold, N., Manning, H., Marchand, G., Marin Jimenez, M., Martin Garcia, C., Martin, D., Martin, M., Martinez-Frias, J., Martin-Soler, J., Martin-Torres, F. J., Mauchien, P., McAdam, A., McCartney, E., McConnochie, T., McCullough, E., McEwan, I., McKay, C., McNair, S., Melikechi, N., Meyer, M., Mezzacappa, A., Miller, H., Miller, K., Milliken, R., Minitti, M., Mischna, M., Mitrofanov, I., Moersch, J., Mokrousov, M., Molina Jurado, A., Moores, J., Mora-Sotomayor, L., Morookian, J. M., Mueller-Mellin, R., Muller, J.-P., Munoz Caro, G., Nachon, M., Navarro Lopez, S., Nealson, K., Nefian, A., Nelson, T., Newcombe, M., Newman, C., Newsom, H., Nikiforov, S., Niles, P., Nixon, B., Dobrea, E. N., Nolan, T., Oehler, D., Ollila, A., Olson, T., Owen, T., Pablo, H., Paillet, A., Pallier, E., Palucis, M., Parker, T., Parot, Y., Patel, K., Paton, M., Paulsen, G., Pavlov, A., Pavri, B., Peinado-Gonzalez, V., Pepin, R., Peret, L., Perez, R., Perrett, G., Peterson, J., Pilorget, C., Pinet, P., Pla-Garcia, J., Plante, I., Poitrasson, F., Polkko, J., Popa, R., Posiolova, L., Pradler, I., Prats, B., Prokhorov, V., Purdy, S. W., Raaen, E., Radziemski, L., Rafkin, S., Ramos, M., Raulin, F., Ravine, M., Reitz, G., Renno, N., Rice, M., Richardson, M., Robert, F., Rodriguez Manfredi, J. A., Romeral-Planello, J. J., Rowland, S., Saccoccio, M., Salamon, A., Sandoval, J., Sanin, A., Sans Fuentes, S. A., Saper, L., Sautter, V., Savijarvi, H., Schieber, J., Schmidt, W., Scholes, D., Schoppers, M., Schroder, S., Sebastian Martinez, E., Sengstacken, A., Shterts, R., Siebach, K., Siili, T., Simmonds, J., Sirven, J.-B., Slavney, S., Sletten, R., Smith, M., Sobron Sanchez, P., Spanovich, N., Spray, J., Squyres, S., Stack, K., Stalport, F., Stein, T., Stern, J., Stewart, N., Stipp, S. L. S., Stoiber, K., Sucharski, B., Summons, R., Sun, V., Supulver, K., Sutter, B., Szopa, C., Tate, C., Teinturier, S., ten Kate, I. L., Thomas, P., Thompson, L., Tokar, R., Toplis, M., Torres Redondo, J., Trainer, M., Tretyakov, V., Urqui-O'Callaghan, R., Van Beek, J., Van Beek, T., VanBommel, S., Varenikov, A., Vasavada, A., Vasconcelos, P., Vicenzi, E., Vostrukhin, A., Voytek, M., Wadhwa, M., Ward, J., Webster, C., Weigle, E., Wellington, D., Westall, F., Wiens, R. C., Wilhelm, M. B., Williams, A., Williams, J., Williams, R., Williams, R. B., Wilson, M., Wimmer-Schweingruber, R., Wolff, M., Wong, M., Wray, J., Wu, M., Yana, C., Zeitlin, C., Zimdar, R., Zorzano Mier, M.-P., GeoRessources, Institut national des sciences de l'Univers (INSU - CNRS)-Centre de recherches sur la géologie des matières premières minérales et énergétiques (CREGU)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), NASA Ames Research Center (ARC), NASA Johnson Space Center (JSC), NASA, Department of Geological Sciences [Austin], Jackson School of Geosciences (JSG), University of Texas at Austin [Austin]-University of Texas at Austin [Austin], Department of Geology [Tucson], University of Arizona, Department of Geological Sciences [Bloomington], Indiana University [Bloomington], Indiana University System-Indiana University System, Malin Space Science Systems (MSSS), NASA Goddard Space Flight Center (GSFC), NWO-NSO: The role of perchlorates in the preservation of organic compounds on Mars, and Petrology

Subjects
Basalt, Meridiani Planum, Multidisciplinary, 010504 meteorology & atmospheric sciences, Curiosity rover, Geochemistry, Mars, [SDU.STU]Sciences of the Universe [physics]/Earth Sciences, Mars Exploration Program, Exploration of Mars, 01 natural sciences, Astrobiology, Impact crater, 13. Climate action, MSL Mars Gale Crater Rocknest, Rocknest, 0103 physical sciences, Sample Analysis at Mars, Aeolian processes, MSL, Rocknest aeolian deposit, 010303 astronomy & astrophysics, Geology, 0105 earth and related environmental sciences
Abstract

The Rocknest aeolian deposit is similar to aeolian features analyzed by the Mars Exploration Rovers (MERs) Spirit and Opportunity. The fraction of sand

Published
2013

9. The Petrochemistry of Jake_M: A Martian Mugearite

Author

Stolper, E. M., Baker, M. B., Newcombe, M. E., Schmidt, M. E., Treiman, A. H., Cousin, A., Dyar, M. D., Fisk, M. R., Gellert, R., King, P. L., Leshin, L., Maurice, S., McLennan, S. M., Minitti, M. E., Perrett, G., Rowland, S., Sautter, V., Wiens, R. C., Kemppinen, O., Bridges, N., Johnson, J. R., Cremers, D., Bell, J. F., Edgar, L., Farmer, J., Godber, A., Wadhwa, M., Wellington, D., McEwan, I., Newman, C., Richardson, M., Charpentier, A., Peret, L., Blank, J., Weigle, G., Li, S., Milliken, R., Robertson, K., Sun, V., Edwards, C., Ehlmann, B., Farley, K., Griffes, J., Grotzinger, J., Miller, H., Pilorget, C., Rice, M., Siebach, K., Stack, K., Brunet, C., Hipkin, V., Leveille, R., Marchand, G., Sanchez, P. S., Favot, L., Cody, G., Steele, A., Fluckiger, L., Lees, D., Nefian, A., Martin, M., Gailhanou, M., Westall, F., Israel, G., Agard, C., Baroukh, J., Donny, C., Gaboriaud, A., Guillemot, P., Lafaille, V., Lorigny, E., Paillet, A., Perez, R., Saccoccio, M., Yana, C., Armiens-Aparicio, C., Rodriguez, J. C., Blazquez, I. C., Gomez, F. G., Gomez-Elvira, J., Hettrich, S., Malvitte, A. L., Jimenez, M. M., Martinez-Frias, J., Martin-Soler, J., Martin-Torres, F. J., Jurado, A. M., Mora-Sotomayor, L., Caro, G. M., Lopez, S. N., Peinado-Gonzalez, V., Pla-Garcia, J., Manfredi, J. A. R., Romeral-Planello, J. J., Fuentes, S. A. S., Martinez, E. S., Redondo, J. T., Urqui-O'Callaghan, R., Mier, M.-P. Z., Chipera, S., Lacour, J.-L., Mauchien, P., Sirven, J.-B., Manning, H., Fairen, A., Hayes, A., Joseph, J., Squyres, S., Sullivan, R., Thomas, P., Dupont, A., Lundberg, A., Melikechi, N., Mezzacappa, A., DeMarines, J., Grinspoon, D., Reitz, G., Prats, B., Atlaskin, E., Genzer, M., Harri, A.-M., Haukka, H., Kahanpaa, H., Kauhanen, J., Paton, M., Polkko, J., Schmidt, W., Siili, T., Fabre, C., Wray, J., Wilhelm, M. B., Poitrasson, F., Patel, K., Gorevan, S., Indyk, S., Paulsen, G., Gupta, S., Bish, D., Schieber, J., Gondet, B., Langevin, Y., Geffroy, C., Baratoux, D., Berger, G., Cros, A., d'Uston, C., Forni, O., Gasnault, O., Lasue, J., Lee, Q.-M., Meslin, P.-Y., Pallier, E., Parot, Y., Pinet, P., Schroder, S., Toplis, M., Lewin, E., Brunner, W., Heydari, E., Achilles, C., Oehler, D., Sutter, B., Cabane, M., Coscia, D., Szopa, C., Teinturier, S., Dromart, G., Robert, F., Le Mouelic, S., Mangold, N., Nachon, M., Buch, A., Stalport, F., Coll, P., Francois, P., Raulin, F., Cameron, J., Clegg, S., DeLapp, D., Dingler, R., Jackson, R. S., Johnstone, S., Lanza, N., Little, C., Nelson, T., Williams, R. B., Kirkland, L., Baker, B., Cantor, B., Caplinger, M., Davis, S., Duston, B., Edgett, K., Fay, D., Hardgrove, C., Harker, D., Herrera, P., Jensen, E., Kennedy, M. R., Krezoski, G., Krysak, D., Lipkaman, L., Malin, M., McCartney, E., McNair, S., Nixon, B., Posiolova, L., Ravine, M., Salamon, A., Saper, L., Stoiber, K., Supulver, K., Van Beek, J., Van Beek, T., Zimdar, R., French, K. L., Iagnemma, K., Miller, K., Summons, R., Goesmann, F., Goetz, W., Hviid, S., Johnson, M., Lefavor, M., Lyness, E., Breves, E., Fassett, C., Blake, D. F., Bristow, T., DesMarais, D., Edwards, L., Haberle, R., Hoehler, T., Hollingsworth, J., Kahre, M., Keely, L., McKay, C., Bleacher, L., Brinckerhoff, W., Choi, D., Conrad, P., Dworkin, J. P., Eigenbrode, J., Floyd, M., Freissinet, C., Garvin, J., Glavin, D., Harpold, D., Mahaffy, P., Martin, D. K., McAdam, A., Pavlov, A., Raaen, E., Smith, M. D., Stern, J., Tan, F., Trainer, M., Meyer, M., Posner, A., Voytek, M., Anderson, R. C., Aubrey, A., Beegle, L. W., Behar, A., Blaney, D., Brinza, D., Calef, F., Christensen, L., Crisp, J., DeFlores, L., Feldman, J., Feldman, S., Flesch, G., Hurowitz, J., Jun, I., Keymeulen, D., Maki, J., Mischna, M., Morookian, J. M., Parker, T., Pavri, B., Schoppers, M., Sengstacken, A., Simmonds, J. J., Spanovich, N., Juarez, M. d. l. T., Vasavada, A., Webster, C. R., Yen, A., Archer, P. D., Cucinotta, F., Jones, J. H., Ming, D., Morris, R. V., Niles, P., Rampe, E., Nolan, T., Radziemski, L., Barraclough, B., Bender, S., Berman, D., Dobrea, E. N., Tokar, R., Vaniman, D., Williams, R. M. E., Yingst, A., Lewis, K., Cleghorn, T., Huntress, W., Manhes, G., Hudgins, J., Olson, T., Stewart, N., Sarrazin, P., Grant, J., Vicenzi, E., Wilson, S. A., Bullock, M., Ehresmann, B., Hamilton, V., Hassler, D., Peterson, J., Rafkin, S., Zeitlin, C., Fedosov, F., Golovin, D., Karpushkina, N., Kozyrev, A., Litvak, M., Malakhov, A., Mitrofanov, I., Mokrousov, M., Nikiforov, S., Prokhorov, V., Sanin, A., Tretyakov, V., Varenikov, A., Vostrukhin, A., Kuzmin, R., Clark, B., Wolff, M., Botta, O., Drake, D., Bean, K., Lemmon, M., Schwenzer, S. P., Anderson, R. B., Herkenhoff, K., Lee, E. M., Sucharski, R., Hernandez, M. A. d. P., Avalos, J. J. B., Ramos, M., Jones, A., Kim, M.-H., Malespin, C., Plante, I., Muller, J.-P., Navarro-Gonzalez, R., Ewing, R., Boynton, W., Downs, R., Fitzgibbon, M., Harshman, K., Morrison, S., Dietrich, W., Kortmann, O., Palucis, M., Sumner, D. Y., Williams, A., Lugmair, G., Wilson, M. A., Rubin, D., Jakosky, B., Balic-Zunic, T., Frydenvang, J., Jensen, J. K., Kinch, K., Koefoed, A., Madsen, M. B., Stipp, S. L. S., Boyd, N., Campbell, J. L., Pradler, I., VanBommel, S., Jacob, S., Owen, T., Savijarvi, H., Boehm, E., Bottcher, S., Burmeister, S., Guo, J., Kohler, J., Garcia, C. M., Mueller-Mellin, R., Wimmer-Schweingruber, R., Bridges, J. C., McConnochie, T., Benna, M., Franz, H., Bower, H., Brunner, A., Blau, H., Boucher, T., Carmosino, M., Atreya, S., Elliott, H., Halleaux, D., Renno, N., Wong, M., Pepin, R., Elliott, B., Spray, J., Thompson, L., Gordon, S., Newsom, H., Ollila, A., Williams, J., Vasconcelos, P., Bentz, J., Nealson, K., Popa, R., Kah, L. C., Moersch, J., Tate, C., Day, M., Kocurek, G., Hallet, B., Sletten, R., Francis, R., McCullough, E., Cloutis, E., ten Kate, I. L., Arvidson, R., Fraeman, A., Scholes, D., Slavney, S., Stein, T., Ward, J., Berger, J., Moores, J. E., GeoRessources, Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre de recherches sur la géologie des matières premières minérales et énergétiques (CREGU)-Institut national des sciences de l'Univers (INSU - CNRS), California Institute of Technology (CALTECH), Department of Earth Sciences [St. Catharines], Brock University [Canada], Lunar and Planetary Institute [Houston] (LPI), Los Alamos National Laboratory (LANL), Institut de recherche en astrophysique et planétologie (IRAP), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Institut de Recherche pour le Développement (IRD)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Météo-France -Centre National de la Recherche Scientifique (CNRS), Mount Holyoke College, Oregon State University (OSU), University of Guelph, Research School of Earth Sciences [Canberra] (RSES), Australian National University (ANU), Rensselaer Polytechnic Institute (RPI), State University of New York (SUNY), Johns Hopkins University Applied Physics Laboratory [Laurel, MD] (APL), University of Hawaii, Institut de minéralogie, de physique des matériaux et de cosmochimie (IMPMC), Muséum national d'Histoire naturelle (MNHN)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de recherche pour le développement [IRD] : UR206-Centre National de la Recherche Scientifique (CNRS), MSL Science Team, Institut national des sciences de l'Univers (INSU - CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Observatoire Midi-Pyrénées (OMP), and Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS)

Subjects
010504 meteorology & atmospheric sciences, Curiosity rover, Geochemistry, Mars, [SDU.STU]Sciences of the Universe [physics]/Earth Sciences, 010502 geochemistry & geophysics, 01 natural sciences, Jake_M: a martian mugearite, chemistry.chemical_compound, Nepheline, MSL, Chemical composition, 0105 earth and related environmental sciences, Martian, Phonolite, Multidisciplinary, Fractional crystallization (geology), petrochemistry, Igneous rock, Planetary science, MSL Mars Petrochemistry, chemistry, 13. Climate action, Petrochemistry, Geology, [SDU.STU.MI]Sciences of the Universe [physics]/Earth Sciences/Mineralogy
Abstract

International audience; "Jake_M," the first rock analyzed by the Alpha Particle X-ray Spectrometer instrument on the Curiosity rover, differs substantially in chemical composition from other known martian igneous rocks: It is alkaline (>15% normative nepheline) and relatively fractionated. Jake_M is compositionally similar to terrestrial mugearites, a rock type typically found at ocean islands and continental rifts. By analogy with these comparable terrestrial rocks, Jake_M could have been produced by extensive fractional crystallization of a primary alkaline or transitional magma at elevated pressure, with or without elevated water contents. The discovery of Jake_M suggests that alkaline magmas may be more abundant on Mars than on Earth and that Curiosity could encounter even more fractionated alkaline rocks (for example, phonolites and trachytes).

Published
2013

10. Volatile, Isotope, and Organic Analysis of Martian Fines with the Mars Curiosity Rover

Author

Leshin, L. A., Mahaffy, P. R., Webster, C. R., Cabane, M., Coll, P., Conrad, P. G., Archer, P. D., Atreya, S. K., Brunner, A. E., Buch, A., Eigenbrode, J. L., Flesch, G. J., Franz, H. B., Freissinet, C., Glavin, D. P., McAdam, A. C., Miller, K. E., Ming, D. W., Morris, R. V., Navarro-Gonzalez, R., Niles, P. B., Owen, T., Pepin, R. O., Squyres, S., Steele, A., Stern, J. C., Summons, R. E., Sumner, D. Y., Sutter, B., Szopa, C., Teinturier, S., Trainer, M. G., Wray, J. J., Grotzinger, J. P., Kemppinen, O., Bridges, N., Johnson, J. R., Minitti, M., Cremers, D., Bell, J. F., Edgar, L., Farmer, J., Godber, A., Wadhwa, M., Wellington, D., McEwan, I., Newman, C., Richardson, M., Charpentier, A., Peret, L., King, P., Blank, J., Weigle, G., Schmidt, M., Li, S., Milliken, R., Robertson, K., Sun, V., Baker, M., Edwards, C., Ehlmann, B., Farley, K., Griffes, J., Miller, H., Newcombe, M., Pilorget, C., Rice, M., Siebach, K., Stack, K., Stolper, E., Brunet, C., Hipkin, V., Leveille, R., Marchand, G., Sanchez, P. S., Favot, L., Cody, G., Fluckiger, L., Lees, D., Nefian, A., Martin, M., Gailhanou, M., Westall, F., Israel, G., Agard, C., Baroukh, J., Donny, C., Gaboriaud, A., Guillemot, P., Lafaille, V., Lorigny, E., Paillet, A., Perez, R., Saccoccio, M., Yana, C., Armiens-Aparicio, C., Rodriguez, J. C., Blazquez, I. C., Gomez, F. G., Gomez-Elvira, J., Hettrich, S., Malvitte, A. L., Jimenez, M. M., Martinez-Frias, J., Martin-Soler, J., Martin-Torres, F. J., Jurado, A. M., Mora-Sotomayor, L., Caro, G. M., Lopez, S. N., Peinado-Gonzalez, V., Pla-Garcia, J., Manfredi, J. A. R., Romeral-Planello, J. J., Fuentes, S. A. S., Martinez, E. S., Redondo, J. T., Urqui-O'Callaghan, R., Mier, M.-P. Z., Chipera, S., Lacour, J.-L., Mauchien, P., Sirven, J.-B., Manning, H., Fairen, A., Hayes, A., Joseph, J., Sullivan, R., Thomas, P., Dupont, A., Lundberg, A., Melikechi, N., Mezzacappa, A., DeMarines, J., Grinspoon, D., Reitz, G., Prats, B., Atlaskin, E., Genzer, M., Harri, A.-M., Haukka, H., Kahanpaa, H., Kauhanen, J., Paton, M., Polkko, J., Schmidt, W., Siili, T., Fabre, C., Wilhelm, M. B., Poitrasson, F., Patel, K., Gorevan, S., Indyk, S., Paulsen, G., Gupta, S., Bish, D., Schieber, J., Gondet, B., Langevin, Y., Geffroy, C., Baratoux, D., Berger, G., Cros, A., d'Uston, C., Forni, O., Gasnault, O., Lasue, J., Lee, Q.-M., Maurice, S., Meslin, P.-Y., Pallier, E., Parot, Y., Pinet, P., Schroder, S., Toplis, M., Lewin, E., Brunner, W., Heydari, E., Achilles, C., Oehler, D., Coscia, D., Dromart, G., Robert, F., Sautter, V., Le Mouelic, S., Mangold, N., Nachon, M., Stalport, F., Francois, P., Raulin, F., Cameron, J., Clegg, S., Cousin, A., DeLapp, D., Dingler, R., Jackson, R. S., Johnstone, S., Lanza, N., Little, C., Nelson, T., Wiens, R. C., Williams, R. B., Jones, A., Kirkland, L., Treiman, A., Baker, B., Cantor, B., Caplinger, M., Davis, S., Duston, B., Edgett, K., Fay, D., Hardgrove, C., Harker, D., Herrera, P., Jensen, E., Kennedy, M. R., Krezoski, G., Krysak, D., Lipkaman, L., Malin, M., McCartney, E., McNair, S., Nixon, B., Posiolova, L., Ravine, M., Salamon, A., Saper, L., Stoiber, K., Supulver, K., Van Beek, J., Van Beek, T., Zimdar, R., French, K. L., Iagnemma, K., Goesmann, F., Goetz, W., Hviid, S., Johnson, M., Lefavor, M., Lyness, E., Breves, E., Dyar, M. D., Fassett, C., Blake, D. F., Bristow, T., DesMarais, D., Edwards, L., Haberle, R., Hoehler, T., Hollingsworth, J., Kahre, M., Keely, L., McKay, C., Bleacher, L., Brinckerhoff, W., Choi, D., Dworkin, J. P., Floyd, M., Garvin, J., Harpold, D., Martin, D. K., Pavlov, A., Raaen, E., Smith, M. D., Tan, F., Meyer, M., Posner, A., Voytek, M., Anderson, R. C., Aubrey, A., Beegle, L. W., Behar, A., Blaney, D., Brinza, D., Calef, F., Christensen, L., Crisp, J. A., DeFlores, L., Feldman, J., Feldman, S., Hurowitz, J., Jun, I., Keymeulen, D., Maki, J., Mischna, M., Morookian, J. M., Parker, T., Pavri, B., Schoppers, M., Sengstacken, A., Simmonds, J. J., Spanovich, N., Juarez, M. d. l. T., Vasavada, A. R., Yen, A., Cucinotta, F., Jones, J. H., Rampe, E., Nolan, T., Fisk, M., Radziemski, L., Barraclough, B., Bender, S., Berman, D., Dobrea, E. N., Tokar, R., Vaniman, D., Williams, R. M. E., Yingst, A., Lewis, K., Cleghorn, T., Huntress, W., Manhes, G., Hudgins, J., Olson, T., Stewart, N., Sarrazin, P., Grant, J., Vicenzi, E., Wilson, S. A., Bullock, M., Ehresmann, B., Hamilton, V., Hassler, D., Peterson, J., Rafkin, S., Zeitlin, C., Fedosov, F., Golovin, D., Karpushkina, N., Kozyrev, A., Litvak, M., Malakhov, A., Mitrofanov, I., Mokrousov, M., Nikiforov, S., Prokhorov, V., Sanin, A., Tretyakov, V., Varenikov, A., Vostrukhin, A., Kuzmin, R., Clark, B., Wolff, M., McLennan, S., Botta, O., Drake, D., Bean, K., Lemmon, M., Schwenzer, S. P., Anderson, R. B., Herkenhoff, K., Lee, E. M., Sucharski, R., Hernandez, M. A. d. P., Avalos, J. J. B., Ramos, M., Kim, M.-H., Malespin, C., Plante, I., Muller, J.-P., Ewing, R., Boynton, W., Downs, R., Fitzgibbon, M., Harshman, K., Morrison, S., Dietrich, W., Kortmann, O., Palucis, M., Williams, A., Lugmair, G., Wilson, M. A., Rubin, D., Jakosky, B., Balic-Zunic, T., Frydenvang, J., Jensen, J. K., Kinch, K., Koefoed, A., Madsen, M. B., Stipp, S. L. S., Boyd, N., Campbell, J. L., Gellert, R., Perrett, G., Pradler, I., VanBommel, S., Jacob, S., Rowland, S., Savijarvi, H., Boehm, E., Bottcher, S., Burmeister, S., Guo, J., Kohler, J., Garcia, C. M., Mueller-Mellin, R., Wimmer-Schweingruber, R., Bridges, J. C., McConnochie, T., Benna, M., Bower, H., Blau, H., Boucher, T., Carmosino, M., Elliott, H., Halleaux, D., Renno, N., Wong, M., Elliott, B., Spray, J., Thompson, L., Gordon, S., Newsom, H., Ollila, A., Williams, J., Vasconcelos, P., Bentz, J., Nealson, K., Popa, R., Kah, L. C., Moersch, J., Tate, C., Day, M., Kocurek, G., Hallet, B., Sletten, R., Francis, R., McCullough, E., Cloutis, E., ten Kate, I. L., Arvidson, R., Fraeman, A., Scholes, D., Slavney, S., Stein, T., Ward, J., Berger, J., Moores, J. E., Department of Earth and Environmental Sciences [Troy, NY], Rensselaer Polytechnic Institute (RPI), NASA Goddard Space Flight Center (GSFC), Jet Propulsion Laboratory (JPL), NASA-California Institute of Technology (CALTECH), PLANETO - LATMOS, Laboratoire Atmosphères, Milieux, Observations Spatiales (LATMOS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Interuniversitaire des Systèmes Atmosphériques (LISA (UMR_7583)), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Astromaterials Research and Exploration Science (ARES), NASA Johnson Space Center (JSC), NASA-NASA, Department of Atmospheric, Oceanic, and Space Sciences [Ann Arbor] (AOSS), University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, Department of Astronomy [College Park], University of Maryland [College Park], University of Maryland System-University of Maryland System, Laboratoire de Génie des Procédés et Matériaux - EA 4038 (LGPM), CentraleSupélec, Center for Research and Exploration in Space Science and Technology [GSFC] (CRESST), Department of Earth, Atmospheric and Planetary Sciences [MIT, Cambridge] (EAPS), Massachusetts Institute of Technology (MIT), Laboratorio de Química de Plasmas y Estudios Planetarios [Mexico], Instituto de Ciencias Nucleares [Mexico], Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM)-Universidad Nacional Autónoma de México = National Autonomous University of Mexico (UNAM), Institute for Astronomy [Honolulu], University of Hawai‘i [Mānoa] (UHM), School of Physics and Astronomy [Minneapolis], University of Minnesota [Twin Cities] (UMN), University of Minnesota System-University of Minnesota System, Cornell University [New York], Geophysical Laboratory [Carnegie Institution], Carnegie Institution for Science, University of California [Davis] (UC Davis), University of California (UC), Jacobs Technology ESCG, Institut Pierre-Simon-Laplace (IPSL), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut national des sciences de l'Univers (INSU - CNRS)-École polytechnique (X)-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), School of Earth and Atmospheric Sciences [Atlanta], Georgia Institute of Technology [Atlanta], Division of Geological and Planetary Sciences [Pasadena], California Institute of Technology (CALTECH), NWO-NSO: The role of perchlorates in the preservation of organic compounds on Mars, Petrology, California Institute of Technology (CALTECH)-NASA, Universidad Nacional Autónoma de México (UNAM)-Universidad Nacional Autónoma de México (UNAM), Carnegie Institution for Science [Washington], University of California, École normale supérieure - Paris (ENS Paris), IMPEC - LATMOS, Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), University of Minnesota [Twin Cities], Cornell University, and École normale supérieure - Paris (ENS Paris)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National d'Études Spatiales [Toulouse] (CNES)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-École polytechnique (X)

Subjects
Martian, Multidisciplinary, 010504 meteorology & atmospheric sciences, [PHYS.ASTR.EP]Physics [physics]/Astrophysics [astro-ph]/Earth and Planetary Astrophysics [astro-ph.EP], Thermal decomposition, Curiosity rover, [SDU.ASTR.EP]Sciences of the Universe [physics]/Astrophysics [astro-ph]/Earth and Planetary Astrophysics [astro-ph.EP], chemistry.chemical_element, Mars, organic analysis, Mars Exploration Program, 01 natural sciences, Astrobiology, chemistry.chemical_compound, chemistry, 13. Climate action, Isotopes of carbon, Rocknest, 0103 physical sciences, Sample Analysis at Mars, Carbonate, MSL Mars Volatiles Isotopes Organics Soil Gale Crater, 010303 astronomy & astrophysics, Carbon, 0105 earth and related environmental sciences
Abstract

Samples from the Rocknest aeolian deposit were heated to ~835°C under helium flow and evolved gases analyzed by Curiosity’s Sample Analysis at Mars instrument suite. H 2 O, SO 2 , CO 2 , and O 2 were the major gases released. Water abundance (1.5 to 3 weight percent) and release temperature suggest that H 2 O is bound within an amorphous component of the sample. Decomposition of fine-grained Fe or Mg carbonate is the likely source of much of the evolved CO 2 . Evolved O 2 is coincident with the release of Cl, suggesting that oxygen is produced from thermal decomposition of an oxychloride compound. Elevated δD values are consistent with recent atmospheric exchange. Carbon isotopes indicate multiple carbon sources in the fines. Several simple organic compounds were detected, but they are not definitively martian in origin.

Published
2013

11. X-ray diffraction results from mars science laboratory: Mineralogy of rocknest at Gale crater

Author

Bish, D. L., Blake, D. F., Vaniman, D. T., Chipera, S. J., Morris, R. V., Ming, D. W., Treiman, A. H., Sarrazin, P., Morrison, S. M., Downs, R. T., Achilles, C. N., Yen, A. S., Bristow, T. F., Crisp, J. A., Morookian, J. M., Farmer, J. D., Rampe, E. B., Stolper, E. M., Spanovich, N., Achilles, C., Agard, C., Verdasca, J. A. A., Anderson, R., Archer, D., Armiens-Aparicio, C., Arvidson, R., Atlaskin, E., Atreya, S., Aubrey, A., Baker, B., Baker, M., Balic-Zunic, T., Baratoux, D., Baroukh, J., Barraclough, B., Bean, K., Beegle, L., Behar, A., Bell, J., Bender, S., Benna, M., Bentz, J., Berger, G., Berger, J., Berman, D., Bish, D., Avalos, J. J. B., Blaney, D., Blank, J., Blau, H., Bleacher, L., Boehm, E., Botta, O., Bottcher, S., Boucher, T., Bower, H., Boyd, N., Boynton, B., Breves, E., Bridges, J., Bridges, N., Brinckerhoff, W., Brinza, D., Bristow, T., Brunet, C., Brunner, A., Brunner, W., Buch, A., Bullock, M., Burmeister, S., Cabane, M., Calef, F., Cameron, J., Campbell, J. I., Cantor, B., Caplinger, M., Rodriguez, J. C., Carmosino, M., Blazquez, I. C., Charpentier, A., Chipera, S., Choi, D., Clark, B., Clegg, S., Cleghorn, T., Cloutis, E., Cody, G., Coll, P., Conrad, P., Coscia, D., Cousin, A., Cremers, D., Crisp, J., Cros, A., Cucinotta, F., d'Uston, C., Davis, S., Day, M. K., Juarez, M. d. l. T., DeFlores, L., DeLapp, D., DeMarines, J., DesMarais, D., Dietrich, W., Dingler, R., Donny, C., Downs, B., Drake, D., Dromart, G., Dupont, A., Duston, B., Dworkin, J., Dyar, M. D., Edgar, L., Edgett, K., Edwards, C., Edwards, L., Ehlmann, B., Ehresmann, B., Eigenbrode, J., Elliott, B., Elliott, H., Ewing, R., Fabre, C., Fairen, A., Farley, K., Farmer, J., Fassett, C., Favot, L., Fay, D., Fedosov, F., Feldman, J., Feldman, S., Fisk, M., Fitzgibbon, M., Flesch, G., Floyd, M., Fluckiger, L., Forni, O., Fraeman, A., Francis, R., Francois, P., Franz, H., Freissinet, C., French, K. L., Frydenvang, J., Gaboriaud, A., Gailhanou, M., Garvin, J., Gasnault, O., Geffroy, C., Gellert, R., Genzer, M., Glavin, D., Godber, A., Goesmann, F., Goetz, W., Golovin, D., Gomez, F. G., Gomez-Elvira, J., Gondet, B., Gordon, S., Gorevan, S., Grant, J., Griffes, J., Grinspoon, D., Grotzinger, J., Guillemot, P., Guo, J., Gupta, S., Guzewich, S., Haberle, R., Halleaux, D., Hallet, B., Hamilton, V., Hardgrove, C., Harker, D., Harpold, D., Harri, A.-M., Harshman, K., Hassler, D., Haukka, H., Hayes, A., Herkenhoff, K., Herrera, P., Hettrich, S., Heydari, E., Hipkin, V., Hoehler, T., Hollingsworth, J., Hudgins, J., Huntress, W., Hurowitz, J., Hviid, S., Iagnemma, K., Indyk, S., Israel, G., Jackson, R., Jacob, S., Jakosky, B., Jensen, E., Jensen, J. K., Johnson, J., Johnson, M., Johnstone, S., Jones, A., Jones, J., Joseph, J., Jun, I., Kah, L., Kahanpaa, H., Kahre, M., Karpushkina, N., Kasprzak, W., Kauhanen, J., Keely, L., Kemppinen, O., Keymeulen, D., Kim, M.-H., Kinch, K., King, P., Kirkland, L., Kocurek, G., Koefoed, A., Kohler, J., Kortmann, O., Kozyrev, A., Krezoski, J., Krysak, D., Kuzmin, R., Lacour, J. L., Lafaille, V., Langevin, Y., Lanza, N., Lasue, J., Le Mouelic, S., Lee, E. M., Lee, Q.-M., Lees, D., Lefavor, M., Lemmon, M., Malvitte, A. L., Leshin, L., Leveille, R., Lewin-Carpintier, E., Lewis, K., Li, S., Lipkaman, L., Little, C., Litvak, M., Lorigny, E., Lugmair, G., Lundberg, A., Lyness, E., Madsen, M., Mahaffy, P., Maki, J., Malakhov, A., Malespin, C., Malin, M., Mangold, N., Manhes, G., Manning, H., Marchand, G., Jimenez, M. M., Garcia, C. M., Martin, D., Martin, M., Martinez-Frias, J., Martin-Soler, J., Martin-Torres, F. J., Mauchien, P., Maurice, S., McAdam, A., McCartney, E., McConnochie, T., McCullough, E., McEwan, I., McKay, C., McLennan, S., McNair, S., Melikechi, N., Meslin, P.-Y., Meyer, M., Mezzacappa, A., Miller, H., Miller, K., Milliken, R., Ming, D., Minitti, M., Mischna, M., Mitrofanov, I., Moersch, J., Mokrousov, M., Jurado, A. M., Moores, J., Mora-Sotomayor, L., Morris, R., Morrison, S., Mueller-Mellin, R., Muller, J.-P., Caro, G. M., Nachon, M., Lopez, S. N., Navarro-Gonzalez, R., Nealson, K., Nefian, A., Nelson, T., Newcombe, M., Newman, C., Newsom, H., Nikiforov, S., Niles, P., Nixon, B., Dobrea, E. N., Nolan, T., Oehler, D., Ollila, A., Olson, T., Owen, T., Hernandez, M. A. d. P., Paillet, A., Pallier, E., Palucis, M., Parker, T., Parot, Y., Patel, K., Paton, M., Paulsen, G., Pavlov, A., Pavri, B., Peinado-Gonzalez, V., Pepin, R., Peret, L., Perez, R., Perrett, G., Peterson, J., Pilorget, C., Pinet, P., Pla-Garcia, J., Plante, I., Poitrasson, F., Polkko, J., Popa, R., Posiolova, L., Posner, A., Pradler, I., Prats, B., Prokhorov, V., Purdy, S. W., Raaen, E., Radziemski, L., Rafkin, S., Ramos, M., Rampe, E., Raulin, F., Ravine, M., Reitz, G., Renno, N., Rice, M., Richardson, M., Robert, F., Robertson, K., Manfredi, J. A. R., Romeral-Planello, J. J., Rowland, S., Rubin, D., Saccoccio, M., Salamon, A., Sandoval, J., Sanin, A., Fuentes, S. A. S., Saper, L., Sautter, V., Savijarvi, H., Schieber, J., Schmidt, M., Schmidt, W., Scholes, D. D., Schoppers, M., Schroder, S., Schwenzer, S., Martinez, E. S., Sengstacken, A., Shterts, R., Siebach, K., Siili, T., Simmonds, J., Sirven, J.-B., Slavney, S., Sletten, R., Smith, M., Sanchez, P. S., Spray, J., Squyres, S., Stack, K., Stalport, F., Steele, A., Stein, T., Stern, J., Stewart, N., Stipp, S. L. S., Stoiber, K., Stolper, E., Sucharski, B., Sullivan, R., Summons, R., Sumner, D., Sun, V., Supulver, K., Sutter, B., Szopa, C., Tan, F., Tate, C., Teinturier, S., ten Kate, I., Thomas, P., Thompson, L., Tokar, R., Toplis, M., Redondo, J. T., Trainer, M., Treiman, A., Tretyakov, V., Urqui-O'Callaghan, R., Van Beek, J., Van Beek, T., VanBommel, S., Vaniman, D., Varenikov, A., Vasavada, A., Vasconcelos, P., Vicenzi, E., Vostrukhin, A., Voytek, M., Wadhwa, M., Ward, J., Webster, C., Weigle, E., Wellington, D., Westall, F., Wiens, R. C., Wilhelm, M. B., Williams, A., Williams, J., Williams, R., Williams, R. B. M., Wilson, M., Wimmer-Schweingruber, R., Wolff, M., Wong, M., Wray, J., Wu, M., Yana, C., Yen, A., Yingst, A., Zeitlin, C., Zimdar, R., Mier, M.-P. Z., GeoRessources, Institut national des sciences de l'Univers (INSU - CNRS)-Centre de recherches sur la géologie des matières premières minérales et énergétiques (CREGU)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), NWO-NSO: The role of perchlorates in the preservation of organic compounds on Mars, and Petrology

Subjects
Multidisciplinary, 010504 meteorology & atmospheric sciences, Water on Mars, Curiosity rover, [SDU.STU]Sciences of the Universe [physics]/Earth Sciences, Mineralogy, Mars, Mars Exploration Program, Martian soil, engineering.material, 01 natural sciences, MSL Mars X-ray Diffraction Mineralogy Rocknest Gale Crater, Meteorite, Impact crater, 13. Climate action, Rocknest, 0103 physical sciences, Pigeonite, engineering, Composition of Mars, MSL, 010303 astronomy & astrophysics, 0105 earth and related environmental sciences, mineralogy of Rocknest at Gale crater
Abstract

The Mars Science Laboratory rover Curiosity scooped samples of soil from the Rocknest aeolian bedform in Gale crater. Analysis of the soil with the Chemistry and Mineralogy (CheMin) x-ray diffraction (XRD) instrument revealed plagioclase (~An57), forsteritic olivine (~Fo62), augite, and pigeonite, with minor K-feldspar, magnetite, quartz, anhydrite, hematite, and ilmenite. The minor phases are present at, or near, detection limits. The soil also contains 27 ± 14 weight percent x-ray amorphous material, likely containing multiple Fe 3+ - and volatile-bearing phases, including possibly a substance resembling hisingerite. The crystalline component is similar to the normative mineralogy of certain basaltic rocks from Gusev crater on Mars and of martian basaltic meteorites. The amorphous component is similar to that found on Earth in places such as soils on the Mauna Kea volcano, Hawaii.

Published
2013

18. Dupilumab prevents nasal epithelial function alteration by IL-4 in vitro: Evidence for its efficacy.

Author

Fieux M, Carsuzaa F, Bellanger Y, Bartier S, Fournier V, Lecron JC, Bainaud M, Louis B, Tringali S, Dufour X, Coste A, Favot L, and Bequignon E

Subjects
Humans, Middle Aged, Female, Adult, Male, Cilia drug effects, Epithelial Cells drug effects, Cells, Cultured, Chronic Disease, Wound Healing drug effects, Interleukin-4 metabolism, Nasal Mucosa drug effects, Antibodies, Monoclonal, Humanized pharmacology, Interleukin-13 metabolism, Nasal Polyps drug therapy, Rhinitis drug therapy, Rhinitis immunology, Sinusitis drug therapy, Sinusitis immunology
Abstract

Background: Chronic rhinosinusitis with nasal polyp (CRSwNP) is a typical type 2 inflammation involving interleukin (IL)-4 and IL-13. Dupilumab is a fully human monoclonal antibody targeting IL-4 receptor α subunit, thereby blocking signaling by both cytokines. Our hypothesis was that IL-4 and IL-13, by inducing a severe epithelial dysregulation, are involved in CRSwNP pathogenesis. This study aimed to evaluate the in vitro direct effect of IL-4, IL-13, and dupilumab on nasal epithelial functions., Methods: Nasal polyps and control mucosa from 28 patients, as well as human nasal epithelial cells (HNEC) from 35 patients with CRSwNP were used. Three major epithelial functions were investigated: the epithelial barrier function (characterized by transepithelial electrical resistance measurements and tight junction protein expression), the ciliary motion (characterized by the ciliary beating efficiency index), and wound healing (characterized by the wound repair rate) under various stimulations (IL-4, IL-13, and dupilumab). The main outcome was a significant change in epithelial functions following exposure to IL-4, IL-13, and dupilumab for 48 h in the basal media., Results: IL-4 (1, 10, and 100 ng/mL) but not IL-13 induced a significant decrease in occludin and zonula-occludens protein expression, ciliary beating efficiency, and wound repair rate in HNEC. Dupilumab (0.04 mg/mL) had no effect on HNEC and specifically restored all epithelial functions altered when cells were exposed to a 48-h IL-4 stimulation., Conclusion: Dupilumab, in vitro, restored epithelial integrity by counteracting the effect of IL-4 on the epithelial barrier (increased epithelial permeability, decreased ciliary beating efficiency, and decreased wound repair rate)., (© 2024 The Authors. International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Published
2024
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20. The M2 macrophages infiltration of sebaceous tumors is linked to the aggressiveness of tumors but not to the mismatch repair pathway.

Author

Frouin E, Alleyrat C, Godet J, Karayan-Tapon L, Sinson H, Morel F, Lecron JC, and Favot L

Subjects
Humans, B7-H1 Antigen genetics, DNA Mismatch Repair, Tumor Microenvironment, Sebaceous Gland Neoplasms genetics, Sebaceous Gland Neoplasms metabolism, Sebaceous Gland Neoplasms pathology, Muir-Torre Syndrome genetics, Neoplastic Syndromes, Hereditary
Abstract

Purpose: The immune microenvironment of sebaceous neoplasms (SNs) has been poorly explored, especially in benign lesions, and never correlated to the mismatch repair (MMR) status., Methods: We conducted an immuno-histological study to analyze the immune microenvironment of SNs. A tissue microarray was constructed including sebaceous adenomas (SAs), sebaceomas (Ss) and sebaceous carcinomas (SCs) to performed immuno-histological analysis of T cells, B cells, macrophages, dendritic cells, and expression of Programmed Death-1 (PD-1) and Programmed Death Ligand 1 (PD-L1). An automatized count was performed using the QuPath® software. Composition of the cellular microenvironment was compared to the aggressiveness, the MMR status, and to Muir-Torre syndrome (MTS)., Results: We included 123 SNs (43 SAs, 19 Ss and 61 SCs) for which 71.5% had a dMMR phenotype. A higher infiltration of macrophages (CD68 +) of M2 phenotype (CD163 +) and dendritic cells (CD11c +) was noticed in SCs compared to benign SNs (SAs and Ss). Programmed cell death ligand-1 but not PD-1 was expressed by more immune cells in SCs compared to benign SNs. No difference in the immune cell composition regarding the MMR status, or to MTS was observed., Conclusion: In SNs, M2 macrophages and dendritic cells infiltrates are associated with the progression and the malignant transformation of tumors. High PD-L1 expression in immune cells in SCs is an argument for the use of immunotherapy by anti-PD1 or PD-L1 in metastatic patients. The lack of correlation between the composition of immune cells in SNs and the MMR status emphasizes the singularity of SNs among MMR-associated malignancies., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Published
2023
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21. Oncostatin M Contributes to Airway Epithelial Cell Dysfunction in Chronic Rhinosinusitis with Nasal Polyps.

Author

Carsuzaa F, Bequignon E, Bartier S, Coste A, Dufour X, Bainaud M, Lecron JC, Louis B, Tringali S, Favot L, and Fieux M

Subjects
Humans, Cells, Cultured, Chronic Disease, Epithelial Cells metabolism, Nasal Mucosa metabolism, Oncostatin M pharmacology, Oncostatin M metabolism, Tight Junctions metabolism, Nasal Polyps, Rhinitis, Sinusitis metabolism
Abstract

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a typical type-2 inflammation involving several cytokines and is associated with epithelial cell dysfunction. Oncostatin M (OSM) (belonging to the interleukin(IL)-6 family) could be a key driver of epithelial barrier dysfunction. Therefore, we investigated the presence of OSM and IL-6 and the expression pattern of tight junctions (TJs) in the nasal tissue of CRSwNP patients and controls using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) and Western blotting. Then, their potential role in the epithelial barrier was evaluated in vitro in 27 different primary cultures of human nasal epithelial cells (HNECs) by measuring TJ expression and transepithelial electric resistance (TEER) with or without OSM or IL-6 (1, 10, and 100 ng/mL). The effect on ciliary beating efficiency was evaluated by high-speed videomicroscopy and on repair mechanisms with a wound healing model with or without OSM. OSM and IL-6 were both overexpressed, and TJ (ZO-1 and occludin) expression was decreased in the nasal polyps compared to the control mucosa. OSM (100 ng/mL) but not IL-6 induced a significant decrease in TJ expression, TEER, and ciliary beating efficiency in HNECs. After 24 h, the wound repair rate was significantly higher in OSM-stimulated HNECs at 100 ng/mL. These results suggest that OSM could become a new target for monoclonal antibodies.

Published
2023
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22. Immunohistochemistry, Molecular Biology, and Clinical Scoring for the Detection of Muir-Torre Syndrome in Cutaneous Sebaceous Tumors: Which Strategy?

Author

Sinson H, Karayan-Tapon L, Godet J, Rivet P, Alleyrat C, Battistella M, Pierron H, Morel F, Lecron JC, Favot L, and Frouin E

Subjects
Humans, Immunohistochemistry, Retrospective Studies, Molecular Biology, Muir-Torre Syndrome diagnosis, Muir-Torre Syndrome genetics, Muir-Torre Syndrome pathology, Sebaceous Gland Neoplasms diagnosis, Sebaceous Gland Neoplasms genetics, Sebaceous Gland Neoplasms pathology, Carcinoma, Basal Cell
Abstract

Background: Sebaceous neoplasms (SNs) always raise the possibility of an association with Muir-Torre syndrome (MTS) and permit to screen internal malignancies, colorectal and endometrial carcinomas, before they become symptomatic. Immunohistochemistry (IHC), molecular biology, and clinical examination are different approaches for detection of MTS. We conducted a retrospective analysis of non-selected SNs in order to determine the optimal tools to implement for MTS screening., Methods: Deficient MMR phenotype (dMMR) was determined by either IHC using antibodies directed to four mismatch repair (MMR) antigens on tissue microarray or molecular biology using pentaplex PCR. The Mayo Clinic risk score of MTS was calculated from medical records. Sensibility and specificity of each test for the detection of MTS were determined., Results: We included 107 patients, 8 with multiple SNs, for a total of 123 SNs (43 sebaceous adenomas, 19 sebaceomas, and 61 sebaceous carcinomas (SC)). Loss of at least one MMR protein was observed in 70.7% of tumors, while 48% had a microsatellite instable phenotype. Concordance between both techniques was 92.9%, with a 0.85 Cohen's kappa coefficient. Nineteen patients (20.2%) had a ≥2 points Mayo Clinic risk score, one having a pMMR SC. Among the 13 patients with confirmed MTS, 2 had a low Mayo Clinic risk score (1 point). IHC had the highest sensitivity for MTS screening (100%) with a specificity of 34.1%, while a >2-point Mayo Clinic risk score had a lower sensitivity (92%) but a higher specificity (89%)., Conclusion: To detect MTS in SN patients, the first-line Mayo Clinic risk score followed by IHC appears to be the most accurate strategy with lower cost for society. This strategy should be adapted to the medico-economic resources of each country., (© 2023 S. Karger AG, Basel.)

Published
2023
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23. Oncostatin M Counteracts the Fibrotic Effects of TGF-β1 and IL-4 on Nasal-Polyp-Derived Fibroblasts: A Control of Fibrosis in Chronic Rhinosinusitis with Nasal Polyps?

Author

Carsuzaa F, Béquignon É, Bainaud M, Jégou JF, Dufour X, Lecron JC, and Favot L

Subjects
Cells, Cultured, Fibroblasts metabolism, Fibrosis, Humans, Interleukin-4 metabolism, Interleukin-4 pharmacology, Oncostatin M metabolism, Oncostatin M pharmacology, Transforming Growth Factor beta1 metabolism, Nasal Polyps genetics, Sinusitis metabolism
Abstract

Chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with inflammation and tissue remodeling including myofibroblasts differentiation and extracellular matrix (ECM) deposition mediated by TGF-β1 and IL-4. Oncostatin M (OSM) is a cytokine involved in fibrotic processes in other cellular subtypes. We investigated the mechanisms of action of OSM in the fibrosis process associated with CRSwNP. The expression of IL-4, OSM and TGF-β1 was assessed by RT-qPCR. Primary human cultures of nasal-polyp-derived fibroblasts were established and stimulated by TGF-β1 and/or IL-4 and/or OSM. The expression of ECM components and αSMA was determined by RT-qPCR and Western blot. TGF-β1-Smad3 signaling was investigated by immunofluorescence. TGF-β1, IL-4 and OSM as well as αSMA were overexpressed in nasal polyps when compared to noninflammatory nasal mucosa. In TGF-β1-stimulated nasal-polyp-derived fibroblasts, ECM genes and αSMA gene and protein were overexpressed, as well as αSMA in IL-4-stimulated fibroblasts. OSM counteracted the profibrotic effect of TGF-β1 on ECM components and αSMA. TGF-β1-induced nuclear translocation of Smad3 was completely reversed by OSM. OSM counteracts the profibrotic effect of IL-4 and also TGF-β1, by inhibiting the nuclear translocation of Smad3. We suggest OSM could be an efficient tool to protect against fibrosis in CRSwNP.

Published
2022
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24. Cytokine Signature and Involvement in Chronic Rhinosinusitis with Nasal Polyps.

Author

Carsuzaa F, Béquignon É, Dufour X, de Bonnecaze G, Lecron JC, and Favot L

Subjects
Animals, Chronic Disease, Humans, Nasal Polyps immunology, Rhinitis immunology, Sinusitis immunology, T-Lymphocytes, Regulatory immunology, Cytokines metabolism, Nasal Polyps complications, Nasal Polyps metabolism, Rhinitis complications, Rhinitis metabolism, Sinusitis complications, Sinusitis metabolism
Abstract

Cytokines are well known to play a central role in chronic rhinosinusitis with nasal polyps (CRSwNP), particularly in maintenance of the inflammatory response and the recruitment of eosinophils. The pathophysiological concepts concerning the involvement of inflammatory cytokines in CRSwNP have gradually evolved. Although the Th2 cytokines environment associated with an eosinophilic infiltration has retained a central role in the genesis of polyps, the role of other cytokine subpopulations has also and more recently been detailed, leading to a specific and complex signature in CRSwNP. The purpose of this review is to summarize the current state of knowledge about the cytokine signature in CRSwNP, the role of cytokines in the pathogenesis of this disease and in the intercellular dialog between epithelial cells, fibroblasts and inflammatory cells. Knowledge of this precise cytokine signature in CRSwNP is fundamental in the perspective of potential targeting biotherapies.

Published
2021
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25. Skin inflammatory response and efficacy of anti-epidermal growth factor receptor therapy in metastatic colorectal cancer (CUTACETUX).

Author

Tougeron D, Emambux S, Favot L, Lecomte T, Wierzbicka-Hainaut E, Samimi M, Frouin E, Azzopardi N, Chevrier J, Serres L, Godet J, Levillain P, Paintaud G, Ferru A, Rouleau L, Delwail A, Silvain C, Tasu JP, Morel F, Ragot S, and Lecron JC

Subjects
Antibodies, Monoclonal therapeutic use, ErbB Receptors therapeutic use, Humans, Prospective Studies, Antineoplastic Agents adverse effects, Colorectal Neoplasms drug therapy
Abstract

Anti-epidermal growth factor receptor (EGFR) monoclonal antibody is a standard treatment of metastatic colorectal cancer (mCRC) and its most common adverse effect is a papulopustular acneiform rash. The aim of the CUTACETUX study was to characterize the skin inflammatory response associated with this rash and its relation to treatment efficacy. This prospective study included patients with mCRC treated with first-line chemotherapy plus cetuximab. Patients underwent skin biopsies before the initiation of cetuximab (D0) and before the third infusion (D28), one in a rash zone and one in an unaffected zone. Expression of Th17-related cytokines (IL-17A, IL-21, IL-22), antimicrobial peptides (S100A7 and BD-2), innate response-related cytokines (IL-1β, IL-6, TNF-α and OSM), T-reg-related cytokines (IL-10 and TGF-β), Th1-related cytokine (IFN-γ), Th2-related cytokine (IL-4), Thymic stromal lymphopoietin and keratinocyte-derived cytokines (IL-8, IL-23 and CCL20) were determined by RT-PCR. Twenty-seven patients were included. Levels of most of the cytokines increased at D28 in the rash zone compared to D0. No significant association was observed between variations of cytokines levels and treatment response in the rash zone and only the increase of IL-4 ( p = .04) and IL-23 ( p = .02) levels between D0 and D28 in the unaffected zone was significantly associated with treatment response. Increased levels of IL-8 ( p = .02), BD-2 ( p = .02), IL-1β ( p = .004) and OSM ( p = .02) in the rash zone were associated with longer progression-free survival. Expression of Th2-related and keratinocyte-derived cytokines in the skin was associated with anti-EGFR efficacy. If this inflammatory signature can explain the rash, the exact mechanism by which these cytokines are involved in anti-EGFR tumor response remains to be studied., (© 2020 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Published
2020
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26. Oncostatin M exerts a protective effect against excessive scarring by counteracting the inductive effect of TGFβ1 on fibrosis markers.

Author

Huguier V, Giot JP, Simonneau M, Levillain P, Charreau S, Garcia M, Jégou JF, Bodet C, Morel F, Lecron JC, and Favot L

Subjects
Adult, Biomarkers metabolism, Case-Control Studies, Cicatrix, Hypertrophic etiology, Cicatrix, Hypertrophic metabolism, Female, Fibroblasts metabolism, Fibroblasts pathology, Fibrosis chemically induced, Follow-Up Studies, Humans, Keloid etiology, Keloid metabolism, Male, Prognosis, Prospective Studies, Wound Healing, Cicatrix, Hypertrophic prevention & control, Fibrosis complications, Growth Inhibitors administration & dosage, Keloid prevention & control, Oncostatin M administration & dosage, Protective Agents administration & dosage, Transforming Growth Factor beta1 adverse effects
Abstract

Wound healing is a complex physiological process that repairs a skin lesion and produces fibrous tissue. In some cases, this process can lead to hypertrophic scars (HS) or keloid scars (KS), for which the pathophysiology remains poorly understood. Previous studies have reported the presence of oncostatin M (OSM) during the wound healing process; however, the role of OSM in pathological scarring remains to be precisely elucidated. This study aims to analyse the presence and involvement of OSM in the pathological scarring process. It was conducted with 18 patients, including 9 patients with hypertrophic scarring and 9 patients with keloid scarring. Histological tissue analysis of HS and KS showed minor differences in the organization of the extracellular matrix, the inflammatory infiltrate and the keratinocyte phenotype. Transcriptomic analysis showed increased expression levels of fibronectin, collagen I, TGFβ1, β-defensin-2 and S100A7 in both pathological samples. OSM expression levels were greater in HS than in KS and control skin. In vitro, OSM inhibited TGFβ1-induced secretion of components of the extracellular matrix by normal and pathological fibroblasts. Overall, we suggest that OSM is involved in pathological wound healing processes by inhibiting the evolution of HS towards KS by controlling the fibrotic effect of TGFβ1.

Published
2019
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27. Persistent Neuroadaptations in the Expression of Genes Involved in Cholesterol Homeostasis Induced by Chronic, Voluntary Alcohol Intake in Rats.

Author

Alsebaaly J, Dugast E, Favot L, Rabbaa Khabbaz L, Solinas M, and Thiriet N

Abstract

Alcohol use disorder (AUD) is associated with persistent adaptations in the brain that are believed to participate in the long-lasting vulnerability to relapse after abstinence. Cholesterol, the major sterol compound found in the central nervous system (CNS), plays a major role in maintenance of neuronal morphology, synaptogenesis and synaptic communication and may be involved in alcohol-induced neuroadaptations. In this study, we investigated whether alcohol consumption in a two-bottle choice paradigm followed by 3 weeks of abstinence could alter the expression of genes encoding proteins involved in cholesterol homeostasis in brain regions involved in addiction and relapse, namely the prefrontal cortex (PFC), the nucleus accumbens (NAc), the mesencephalon and the amygdala. We found that voluntary alcohol intake followed by 3 weeks of forced abstinence produces changes in the transcription of several genes encoding proteins directly involved in cholesterol synthesis such as 3-hydroxyl-3-methylglutaryl-coenzyme A (HMGCoA) reductase, farnesyl-diphosphate farnesyltransferase 1 (FDFT1) and farnesyl diphosphate synthase (FDPS) and in its regulation such as sterol regulatory element-binding factor-2 (SREBF2), in cholesterol transport such as ATP-binding cassette subfamily A member 1 (ABCA1) and in cholesterol degradation such as CYP46A1. Interestingly, these changes appeared to be region-specific and suggest that previous chronic exposure to alcohol might durably increase cholesterol metabolism in the PFC, the NAc and the mesencephalon and decrease cholesterol metabolism in the amygdala. Altogether, these results suggest that alcohol consumption leads to durable deregulations in cholesterol metabolism in key areas involved in loss of control over drug use and addiction. These long-term neuroadaptations may participate in the changes in brain structure and functioning that are responsible for the long-lasting risks of relapse to alcohol.

Published
2018
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28. Oncostatin M is overexpressed in skin squamous-cell carcinoma and promotes tumor progression.

Author

Simonneau M, Frouin E, Huguier V, Jermidi C, Jégou JF, Godet J, Barra A, Paris I, Levillain P, Cordier-Dirikoc S, Pedretti N, Bernard FX, Lecron JC, Morel F, and Favot L

Abstract

Cutaneous squamous cell carcinoma (cSCC) is the second most common keratinocyte malignancy and accounts for 20% of skin cancer deaths. Cancer is closely related to inflammation, but the contribution of the tumor microenvironment to cSCC development is poorly understood. We previously showed that oncostatin M (OSM), a cytokine belonging to the IL-6 family, promotes normal keratinocyte proliferation and migration, skin inflammation, and epidermal hyperplasia, both in vitro and in vivo . Here, we show that OSM is overexpressed in human cSCC and is associated with type 1 immune polarization. In vitro , OSM induced STAT-3 and ERK signaling, modified the expression of genes involved in cytokine signaling, proliferation, inhibition of apoptosis, and immune responses, and promoted proliferation and migration of malignant keratinocyte PDVC57 cells. PDVC57 cells grafted in the skin of mice led to rapid cSCC development, associated with OSM expression by tumor-infiltrating neutrophils. Finally, the absence of OSM (OSM-KO mice) led to a 30% reduction of tumor size and reduced M2 polarization in the tumor microenvironment. Globally, these results support a pro-tumoral role of OSM in cSCC development and suggest that a new therapeutic approach targeting this cytokine could be considered., Competing Interests: CONFLICTS OF INTEREST The authors have no conflicts of interest to declare.

Published
2018
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29. Development of a new model of reconstituted mouse epidermis and characterization of its response to proinflammatory cytokines.

Author

Pohin M, Veaute C, Garnier J, Barrault C, Cronier L, Huguier V, Favot L, Mcheik J, Bernard FX, Lecron JC, Morel F, and Jégou JF

Subjects
Adherens Junctions drug effects, Adherens Junctions metabolism, Animals, Animals, Newborn, Biomarkers metabolism, Cell Differentiation drug effects, Filaggrin Proteins, Gap Junctions drug effects, Gap Junctions metabolism, Mice, Inbred C57BL, Morphogenesis drug effects, Receptors, Cytokine metabolism, Cytokines toxicity, Epidermis drug effects, Inflammation Mediators toxicity, Models, Biological
Abstract

The development of three-dimensional models of reconstituted mouse epidermis (RME) has been hampered by the difficulty to maintain murine primary keratinocyte cultures and to achieve a complete epidermal stratification. In this study, a new protocol is proposed for the rapid and convenient generation of RME, which reproduces accurately the architecture of a normal mouse epidermis. During RME morphogenesis, the expression of differentiation markers such as keratins, loricrin, filaggrin, E-cadherin and connexins was followed, showing that RME structure at day 5 was similar to those of a normal mouse epidermis, with the acquisition of the natural barrier function. It was also demonstrated that RME responded to skin-relevant proinflammatory cytokines by increasing the expression of antimicrobial peptides and chemokines, and inhibiting epidermal differentiation markers, as in the human system. This new model of RME is therefore suitable to investigate mouse epidermis physiology further and opens new perspectives to generate reconstituted epidermis from transgenic mice., (Copyright © 2017 John Wiley & Sons, Ltd.)

Published
2018
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30. Characterization of skin Th17 transcriptional profiles in psoriatic patients under adalimumab biotherapy.

Author

Buffiere-Morgado A, Couderc E, Delwail A, Favot L, Jegou JF, Solau E, Guillet G, Lecron JC, and Morel F

Subjects
Antibodies, Monoclonal, Biological Therapy, Gene Expression Profiling, Humans, Membrane Glycoproteins metabolism, Psoriasis metabolism, RNA, Long Noncoding, RNA, Messenger metabolism, Severity of Illness Index, Skin metabolism, Statistics, Nonparametric, Th17 Cells, Treatment Outcome, Adalimumab therapeutic use, Anti-Inflammatory Agents therapeutic use, Cytokines metabolism, Psoriasis drug therapy, Psoriasis immunology, Skin immunology
Abstract

In psoriasis, a specific cytokine network has been described to play a central role in the pathophysiology of the disease. Anti-cytokine therapeutic approaches have been largely developed and TNFα constitutes the main target. Adalimumab is a human anti-TNFα monoclonal antibody that has been reported to demonstrate clinical efficacy and safety, resulting in reversal of epidermal hyperplasia and cutaneous inflammation. We aimed to analyse changes in the skin inflammatory transcriptomic profile in psoriatic patients during adalimumab therapy. In addition, the circulating cytokine profile was analysed to define systemic inflammation. Eighteen patients with chronic plaque psoriasis were treated with adalimumab. After four and 16 weeks, clinical efficacy was assessed using PASI and DLQI, and skin mRNA profiles were determined and circulating cytokines quantified. We identified a rapid effect of adalimumab therapy on a large array of Th17 cytokines of the skin, which may account for the modification of keratinocyte expression profile and clinical response. In contrast, analysis of serum cytokine concentrations was uninformative, confirming the need for characterization of local cytokines in skin lesions. Finally, in non-responders, local cytokine expression was shown to be unchanged. We show that TNFα inhibition in psoriasis patients treated with adalimumab has a broad effect on the expression profile of cytokines and keratinocyte markers of skin inflammation, which may account for its clinical efficacy.

Published
2017
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31. Interleukin-17A-induced production of acute serum amyloid A by keratinocytes contributes to psoriasis pathogenesis.

Author

Couderc E, Morel F, Levillain P, Buffière-Morgado A, Camus M, Paquier C, Bodet C, Jégou JF, Pohin M, Favot L, Garcia M, Huguier V, Mcheik J, Lacombe C, Yssel H, Guillet G, Bernard FX, and Lecron JC

Subjects
Adult, Aged, Aminoquinolines pharmacology, Animals, Cells, Cultured, Chemokine CCL20 metabolism, Chemokine CCL20 pharmacology, Cytokines genetics, Cytokines metabolism, Dermatitis, Atopic metabolism, Disease Models, Animal, Female, Humans, Imiquimod, Interleukin-17 genetics, Interleukin-17 metabolism, Keratinocytes cytology, Keratinocytes drug effects, Keratinocytes metabolism, Liver drug effects, Liver metabolism, Male, Mice, Mice, Inbred C57BL, Middle Aged, Psoriasis metabolism, Receptors, CCR6 metabolism, Recombinant Proteins biosynthesis, Recombinant Proteins isolation & purification, Recombinant Proteins pharmacology, Serum Amyloid A Protein analysis, Serum Amyloid A Protein genetics, Skin metabolism, Th17 Cells cytology, Th17 Cells metabolism, Dermatitis, Atopic pathology, Interleukin-17 pharmacology, Psoriasis pathology, Serum Amyloid A Protein metabolism, Skin drug effects, Up-Regulation drug effects
Abstract

Background: Acute-serum Amyloid A (A-SAA), one of the major acute-phase proteins, is mainly produced in the liver but extra-hepatic synthesis involving the skin has been reported. Its expression is regulated by the transcription factors NF-κB, C/EBPβ, STAT3 activated by proinflammatory cytokines., Objectives: We investigated A-SAA synthesis by resting and cytokine-activated Normal Human Epidermal Keratinocytes (NHEK), and their inflammatory response to A-SAA stimulation. A-SAA expression was also studied in mouse skin and liver in a model mimicking psoriasis and in the skin and sera of psoriatic and atopic dermatitis (AD) patients., Methods: NHEK were stimulated by A-SAA or the cytokines IL-1α, IL-17A, IL-22, OSM, TNF-α alone or in combination, previously reported to reproduce features of psoriasis. Murine skins were treated by imiquimod cream. Human skins and sera were obtained from patients with psoriasis and AD. A-SAA mRNA was quantified by RT qPCR. A-SAA proteins were dosed by ELISA or immunonephelemetry assay., Results: IL-1α, TNF-α and mainly IL-17A induced A-SAA expression by NHEK. A-SAA induced its own production and the synthesis of hBD2 and CCL20, both ligands for CCR6, a chemokine receptor involved in the trafficking of Th17 lymphocytes. A-SAA expression was increased in skins and livers from imiquimod-treated mice and in patient skins with psoriasis, but not significantly in those with AD. Correlations between A-SAA and psoriasis severity and duration were observed., Conclusion: Keratinocytes could contribute to psoriasis pathogenesis via A-SAA production, maintaining a cutaneous inflammatory environment, activating innate immunity and Th17 lymphocyte recruitment.

Published
2017
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32. High-Fat Diet-Induced IL-17A Exacerbates Psoriasiform Dermatitis in a Mouse Model of Steatohepatitis.

Author

Vasseur P, Serres L, Jégou JF, Pohin M, Delwail A, Petit-Paris I, Levillain P, Favot L, Samson M, Yssel H, Morel F, Silvain C, and Lecron JC

Subjects
Animals, Dermatitis complications, Diet, High-Fat adverse effects, Disease Models, Animal, Flow Cytometry, Fluorescent Antibody Technique, Male, Mice, Mice, Inbred C57BL, Non-alcoholic Fatty Liver Disease complications, Real-Time Polymerase Chain Reaction, Dermatitis pathology, Interleukin-17 metabolism, Non-alcoholic Fatty Liver Disease pathology
Abstract

Recent studies suggest that psoriasis may be more severe in patients with nonalcoholic fatty liver disease, particularly in those with the inflammatory stage of steatohepatitis [nonalcoholic steatohepatitis (NASH)]. Herein, we investigated the impact of diet-induced steatohepatitis on the severity of imiquimod-induced psoriasiform dermatitis. Mice fed with a high-fat diet developed steatohepatitis reminiscent of human NASH with ballooning hepatocytes and significant liver fibrosis. Mice with steatohepatitis also displayed moderate cutaneous inflammation characterized by erythema, dermal infiltrates of CD45(+) leukocytes, and a local production of IL-17A. Moreover, steatohepatitis was associated with an epidermal activation of caspase-1 and cutaneous overexpression of IL-1β. Imiquimod-induced psoriasiform dermatitis was exacerbated in mice with steatohepatitis as compared to animals fed with a standard diet. Scale formation and acanthosis were aggravated, in correlation with increased IL-17A and IL-22 expression in inflamed skins. Finally, intradermal injection of IL-17A in standard diet-fed mice recapitulated the cutaneous pathology of mice with steatohepatitis. The results show that high-fat diet-induced steatohepatitis aggravates the inflammation in psoriasiform dermatitis, via the cutaneous production of IL-17A. In agreement with clinical data, this description of a novel extrahepatic manifestation of NASH should sensitize dermatologists to the screening and the management of fatty liver in psoriatic patients., (Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Published
2016
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33. Oncostatin M overexpression induces skin inflammation but is not required in the mouse model of imiquimod-induced psoriasis-like inflammation.

Author

Pohin M, Guesdon W, Mekouo AA, Rabeony H, Paris I, Atanassov H, Favot L, Mcheik J, Bernard FX, Richards CD, Amiaud J, Blanchard F, Lecron JC, Morel F, and Jégou JF

Subjects
Animals, Biomarkers, Cell Differentiation genetics, Cell Proliferation, Disease Models, Animal, Epidermis immunology, Epidermis metabolism, Epidermis pathology, Filaggrin Proteins, Gene Expression Regulation, Imiquimod, Keratinocytes cytology, Keratinocytes metabolism, Keratinocytes pathology, Male, Mice, Mice, Knockout, Phenotype, Psoriasis pathology, Skin immunology, Skin metabolism, Skin pathology, Aminoquinolines adverse effects, Gene Expression, Oncostatin M genetics, Psoriasis etiology, Psoriasis metabolism
Abstract

Oncostatin M (OSM) has been reported to be overexpressed in psoriasis skin lesions and to exert proinflammatory effects in vitro on human keratinocytes. Here, we report the proinflammatory role of OSM in vivo in a mouse model of skin inflammation induced by intradermal injection of murine OSM-encoding adenovirus (AdOSM) and compare with that induced by IL-6 injection. Here, we show that OSM potently regulates the expression of genes involved in skin inflammation and epidermal differentiation in murine primary keratinocytes. In vivo, intradermal injection of AdOSM in mouse ears provoked robust skin inflammation with epidermal thickening and keratinocyte proliferation, while minimal effect was observed after AdIL-6 injection. OSM overexpression in the skin increased the expression of the S100A8/9 antimicrobial peptides, CXCL3, CCL2, CCL5, CCL20, and Th1/Th2 cytokines, in correlation with neutrophil and macrophage infiltration. In contrast, OSM downregulated the expression of epidermal differentiation genes, such as cytokeratin-10 or filaggrin. Collectively, these results support the proinflammatory role of OSM when it is overexpressed in the skin. However, OSM expression was not required in the murine model of psoriasis induced by topical application of imiquimod, as demonstrated by the inflammatory phenotype of OSM-deficient mice or wild-type mice treated with anti-OSM antibodies., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Published
2016
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34. Delphinidin Inhibits Tumor Growth by Acting on VEGF Signalling in Endothelial Cells.

Author

Keravis T, Favot L, Abusnina AA, Anton A, Justiniano H, Soleti R, Alabed Alibrahim E, Simard G, Andriantsitohaina R, and Lugnier C

Subjects
Angiogenesis Inhibitors pharmacology, Animals, Anthocyanins pharmacology, Cell Line, Tumor, Cell Proliferation drug effects, Endothelial Cells drug effects, Endothelial Cells metabolism, Human Umbilical Vein Endothelial Cells, Male, Melanoma metabolism, Melanoma pathology, Mice, Phosphorylation drug effects, Xenograft Model Antitumor Assays, Angiogenesis Inhibitors administration & dosage, Anthocyanins administration & dosage, Endothelial Cells cytology, Melanoma drug therapy, Signal Transduction drug effects, Vascular Endothelial Growth Factor A metabolism
Abstract

The vasculoprotective properties of delphinidin are driven mainly by its action on endothelial cells. Moreover, delphinidin displays anti-angiogenic properties in both in vitro and in vivo angiogenesis models and thereby might prevent the development of tumors associated with excessive vascularization. This study was aimed to test the effect of delphinidin on melanoma-induced tumor growth with emphasis on its molecular mechanism on endothelial cells. Delphinidin treatment significantly decreased in vivo tumor growth induced by B16-F10 melanoma cell xenograft in mice. In vitro, delphinidin was not able to inhibit VEGFR2-mediated B16-F10 melanoma cell proliferation but it specifically reduced basal and VEGFR2-mediated endothelial cell proliferation. The anti-proliferative effect of delphinidin was reversed either by the MEK1/2 MAP kinase inhibitor, U-0126, or the PI3K inhibitor, LY-294002. VEGF-induced proliferation was reduced either by U-0126 or LY-294002. Under these conditions, delphinidin failed to decrease further endothelial cell proliferation. Delphinidin prevented VEGF-induced phosphorylation of ERK1/2 and p38 MAPK and decreased the expression of the transcription factors, CREB and ATF1. Finally, delphinidin was more potent in inhibiting in vitro cyclic nucleotide phosphodiesterases (PDEs), PDE1 and PDE2, compared to PDE3-PDE5. Altogether delphinidin reduced tumor growth of melanoma cell in vivo by acting specifically on endothelial cell proliferation. The mechanism implies an association between inhibition of VEGF-induced proliferation via VEGFR2 signalling, MAPK, PI3K and at transcription level on CREB/ATF1 factors, and the inhibition of PDE2. In conjunction with our previous studies, we demonstrate that delphinidin is a promising compound to prevent pathologies associated with generation of vascular network in tumorigenesis.

Published
2015
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35. IMQ-induced skin inflammation in mice is dependent on IL-1R1 and MyD88 signaling but independent of the NLRP3 inflammasome.

Author

Rabeony H, Pohin M, Vasseur P, Petit-Paris I, Jégou JF, Favot L, Frouin E, Boutet MA, Blanchard F, Togbe D, Ryffel B, Bernard FX, Lecron JC, and Morel F

Subjects
Adjuvants, Immunologic pharmacology, Aminoquinolines pharmacology, Animals, Carrier Proteins genetics, Cytokines genetics, Cytokines immunology, Drug Eruptions genetics, Drug Eruptions pathology, Imiquimod, Inflammasomes genetics, Membrane Glycoproteins genetics, Membrane Glycoproteins immunology, Mice, Mice, Knockout, Myeloid Differentiation Factor 88 genetics, NLR Family, Pyrin Domain-Containing 3 Protein, Receptors, Interleukin-1 Type I genetics, Signal Transduction drug effects, Signal Transduction genetics, Skin immunology, Skin pathology, Toll-Like Receptor 7 genetics, Toll-Like Receptor 7 immunology, Adjuvants, Immunologic adverse effects, Aminoquinolines adverse effects, Carrier Proteins immunology, Drug Eruptions immunology, Inflammasomes immunology, Myeloid Differentiation Factor 88 immunology, Receptors, Interleukin-1 Type I immunology, Signal Transduction immunology
Abstract

The pathogenesis of inflammatory skin diseases such as psoriasis involves the release of numerous proinflammatory cytokines, including members of the IL-1 family. Here we report overexpression of IL-1α, IL-1β, and IL-1 receptor antagonist mRNA, associated to expression of IL-23p19, IL-17A, and IL-22 in skin cells, upon topical application of the TLR7 agonist imiquimod (IMQ) in C57BL/6J mice. IMQ-induced skin inflammation was partially reduced in mice deficient for both IL-1α/IL-1β or for IL-1 receptor type 1 (IL-1R1), but not in IL-1α- or IL-1β-deficient mice, demonstrating the redundant activity of IL-1α and IL-1β for skin inflammation. NLRP3 or apoptosis-associated Speck-like protein containing a Caspase recruitment domain-deficient mice had no significant reduction of skin inflammation in response to IMQ treatment, mainly due to the redundancy of IL-1α. However, IMQ-induced skin inflammation was abolished in the absence of MyD88, the adaptor protein shared by IL-1R and TLR signaling pathways. These results are consistent with the TLR7 dependence of IMQ-induced skin inflammation. Thus, IL-1R1 contributes to the IMQ-induced skin inflammation, and disruption of MyD88 signaling completely abrogates this response., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Published
2015
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37. Isotope ratios of H, C, and O in CO2 and H2O of the martian atmosphere.

Author

Webster CR, Mahaffy PR, Flesch GJ, Niles PB, Jones JH, Leshin LA, Atreya SK, Stern JC, Christensen LE, Owen T, Franz H, Pepin RO, Steele A, Achilles C, Agard C, Alves Verdasca JA, Anderson R, Anderson R, Archer D, Armiens-Aparicio C, Arvidson R, Atlaskin E, Aubrey A, Baker B, Baker M, Balic-Zunic T, Baratoux D, Baroukh J, Barraclough B, Bean K, Beegle L, Behar A, Bell J, Bender S, Benna M, Bentz J, Berger G, Berger J, Berman D, Bish D, Blake DF, Blanco Avalos JJ, Blaney D, Blank J, Blau H, Bleacher L, Boehm E, Botta O, Böttcher S, Boucher T, Bower H, Boyd N, Boynton B, Breves E, Bridges J, Bridges N, Brinckerhoff W, Brinza D, Bristow T, Brunet C, Brunner A, Brunner W, Buch A, Bullock M, Burmeister S, Cabane M, Calef F, Cameron J, Campbell J, Cantor B, Caplinger M, Caride Rodríguez J, Carmosino M, Carrasco Blázquez I, Charpentier A, Chipera S, Choi D, Clark B, Clegg S, Cleghorn T, Cloutis E, Cody G, Coll P, Conrad P, Coscia D, Cousin A, Cremers D, Crisp J, Cros A, Cucinotta F, d'Uston C, Davis S, Day M, de la Torre Juarez M, DeFlores L, DeLapp D, DeMarines J, DesMarais D, Dietrich W, Dingler R, Donny C, Downs B, Drake D, Dromart G, Dupont A, Duston B, Dworkin J, Dyar MD, Edgar L, Edgett K, Edwards C, Edwards L, Ehlmann B, Ehresmann B, Eigenbrode J, Elliott B, Elliott H, Ewing R, Fabre C, Fairén A, Farley K, Farmer J, Fassett C, Favot L, Fay D, Fedosov F, Feldman J, Feldman S, Fisk M, Fitzgibbon M, Floyd M, Flückiger L, Forni O, Fraeman A, Francis R, François P, Freissinet C, French KL, Frydenvang J, Gaboriaud A, Gailhanou M, Garvin J, Gasnault O, Geffroy C, Gellert R, Genzer M, Glavin D, Godber A, Goesmann F, Goetz W, Golovin D, Gómez Gómez F, Gómez-Elvira J, Gondet B, Gordon S, Gorevan S, Grant J, Griffes J, Grinspoon D, Grotzinger J, Guillemot P, Guo J, Gupta S, Guzewich S, Haberle R, Halleaux D, Hallet B, Hamilton V, Hardgrove C, Harker D, Harpold D, Harri AM, Harshman K, Hassler D, Haukka H, Hayes A, Herkenhoff K, Herrera P, Hettrich S, Heydari E, Hipkin V, Hoehler T, Hollingsworth J, Hudgins J, Huntress W, Hurowitz J, Hviid S, Iagnemma K, Indyk S, Israël G, Jackson R, Jacob S, Jakosky B, Jensen E, Jensen JK, Johnson J, Johnson M, Johnstone S, Jones A, Joseph J, Jun I, Kah L, Kahanpää H, Kahre M, Karpushkina N, Kasprzak W, Kauhanen J, Keely L, Kemppinen O, Keymeulen D, Kim MH, Kinch K, King P, Kirkland L, Kocurek G, Koefoed A, Köhler J, Kortmann O, Kozyrev A, Krezoski J, Krysak D, Kuzmin R, Lacour JL, Lafaille V, Langevin Y, Lanza N, Lasue J, Le Mouélic S, Lee EM, Lee QM, Lees D, Lefavor M, Lemmon M, Lepinette Malvitte A, Léveillé R, Lewin-Carpintier É, Lewis K, Li S, Lipkaman L, Little C, Litvak M, Lorigny E, Lugmair G, Lundberg A, Lyness E, Madsen M, Maki J, Malakhov A, Malespin C, Malin M, Mangold N, Manhes G, Manning H, Marchand G, Marín Jiménez M, Martín García C, Martin D, Martin M, Martínez-Frías J, Martín-Soler J, Martín-Torres FJ, Mauchien P, Maurice S, McAdam A, McCartney E, McConnochie T, McCullough E, McEwan I, McKay C, McLennan S, McNair S, Melikechi N, Meslin PY, Meyer M, Mezzacappa A, Miller H, Miller K, Milliken R, Ming D, Minitti M, Mischna M, Mitrofanov I, Moersch J, Mokrousov M, Molina Jurado A, Moores J, Mora-Sotomayor L, Morookian JM, Morris R, Morrison S, Mueller-Mellin R, Muller JP, Muñoz Caro G, Nachon M, Navarro López S, Navarro-González R, Nealson K, Nefian A, Nelson T, Newcombe M, Newman C, Newsom H, Nikiforov S, Nixon B, Noe Dobrea E, Nolan T, Oehler D, Ollila A, Olson T, de Pablo Hernández MÁ, Paillet A, Pallier E, Palucis M, Parker T, Parot Y, Patel K, Paton M, Paulsen G, Pavlov A, Pavri B, Peinado-González V, Peret L, Perez R, Perrett G, Peterson J, Pilorget C, Pinet P, Pla-García J, Plante I, Poitrasson F, Polkko J, Popa R, Posiolova L, Posner A, Pradler I, Prats B, Prokhorov V, Purdy SW, Raaen E, Radziemski L, Rafkin S, Ramos M, Rampe E, Raulin F, Ravine M, Reitz G, Rennó N, Rice M, Richardson M, Robert F, Robertson K, Rodriguez Manfredi JA, Romeral-Planelló JJ, Rowland S, Rubin D, Saccoccio M, Salamon A, Sandoval J, Sanin A, Sans Fuentes SA, Saper L, Sarrazin P, Sautter V, Savijärvi H, Schieber J, Schmidt M, Schmidt W, Scholes D, Schoppers M, Schröder S, Schwenzer S, Sebastian Martinez E, Sengstacken A, Shterts R, Siebach K, Siili T, Simmonds J, Sirven JB, Slavney S, Sletten R, Smith M, Sobrón Sánchez P, Spanovich N, Spray J, Squyres S, Stack K, Stalport F, Stein T, Stewart N, Stipp SL, Stoiber K, Stolper E, Sucharski B, Sullivan R, Summons R, Sumner D, Sun V, Supulver K, Sutter B, Szopa C, Tan F, Tate C, Teinturier S, ten Kate I, Thomas P, Thompson L, Tokar R, Toplis M, Torres Redondo J, Trainer M, Treiman A, Tretyakov V, Urqui-O'Callaghan R, Van Beek J, Van Beek T, VanBommel S, Vaniman D, Varenikov A, Vasavada A, Vasconcelos P, Vicenzi E, Vostrukhin A, Voytek M, Wadhwa M, Ward J, Weigle E, Wellington D, Westall F, Wiens RC, Wilhelm MB, Williams A, Williams J, Williams R, Williams RB, Wilson M, Wimmer-Schweingruber R, Wolff M, Wong M, Wray J, Wu M, Yana C, Yen A, Yingst A, Zeitlin C, Zimdar R, and Zorzano Mier MP

Abstract

Stable isotope ratios of H, C, and O are powerful indicators of a wide variety of planetary geophysical processes, and for Mars they reveal the record of loss of its atmosphere and subsequent interactions with its surface such as carbonate formation. We report in situ measurements of the isotopic ratios of D/H and (18)O/(16)O in water and (13)C/(12)C, (18)O/(16)O, (17)O/(16)O, and (13)C(18)O/(12)C(16)O in carbon dioxide, made in the martian atmosphere at Gale Crater from the Curiosity rover using the Sample Analysis at Mars (SAM)'s tunable laser spectrometer (TLS). Comparison between our measurements in the modern atmosphere and those of martian meteorites such as ALH 84001 implies that the martian reservoirs of CO2 and H2O were largely established ~4 billion years ago, but that atmospheric loss or surface interaction may be still ongoing.

Published
2013
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38. Involvement of IL-1 and oncostatin M in acanthosis associated with hypertensive leg ulcer.

Author

Giot JP, Paris I, Levillain P, Huguier V, Charreau S, Delwail A, Garcia M, Garnier J, Bernard FX, Dagregorio G, Guillet G, Morel F, Lecron JC, and Favot L

Subjects
Adult, Aged, Animals, Cell Differentiation, Cell Proliferation, Constriction, Pathologic complications, Constriction, Pathologic pathology, Epidermis pathology, Female, Humans, Hypertension metabolism, Hypertension pathology, Interleukin-6 metabolism, Keratin-10 metabolism, Keratinocytes metabolism, Keratinocytes pathology, Ki-67 Antigen metabolism, Leg Ulcer metabolism, Leukocytes pathology, Male, Melanosis metabolism, Mice, Mice, Inbred C57BL, Microvessels pathology, Models, Biological, Muscle, Smooth, Vascular pathology, Myocytes, Smooth Muscle metabolism, Myocytes, Smooth Muscle pathology, Hypertension complications, Interleukin-1beta metabolism, Leg Ulcer complications, Leg Ulcer pathology, Melanosis complications, Melanosis pathology, Oncostatin M metabolism
Abstract

Hypertensive leg ulcer (HLU) is an inflammatory disease characterized by intense pain, alteration of vascularization, and skin necrosis. The optimal treatment relies on surgical removal of necrotic tissues covered by a split-skin graft. We studied the histomorphology of the lesions and investigated the involvement of inflammatory cells and cytokines to further define the physiopathology of HLU. We report epidermis acanthosis and a preferential occlusion of the precapillary arterioles with infiltration of neutrophils, macrophages, and T lymphocytes in the dermis. OSM, IL-1β, and IL-6 were overexpressed in the ulcer, whereas the Th17-derived cytokines were not. In vitro, the addition of IL-1β and OSM promoted acanthosis and destructuring of reconstructed epidermis. Exogenous IL-1β and OSM synergistically induced epidermal acanthosis in mice. These data show that OSM and IL-1β are not only a biological characteristic signature of HLU, but these cytokines reflect a specific inflammatory state, directly involved in the pathogenesis. We suggest that anti-cytokine biotherapies could be an alternative strategy to surgery to treat HLU., (Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Published
2013
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39. Loss of environmental enrichment increases vulnerability to cocaine addiction.

Author

Nader J, Chauvet C, Rawas RE, Favot L, Jaber M, Thiriet N, and Solinas M

Subjects
Animals, Behavior, Addictive genetics, Behavior, Addictive metabolism, Behavior, Animal drug effects, Cocaine pharmacology, Cocaine-Related Disorders genetics, Corticotropin-Releasing Hormone genetics, Dopamine Uptake Inhibitors pharmacology, Housing, Animal, Male, Mice, Nucleus Accumbens metabolism, Phosphorylation drug effects, Septal Nuclei metabolism, Cocaine-Related Disorders metabolism, Corticotropin-Releasing Hormone metabolism, Cyclic AMP Response Element-Binding Protein metabolism, Environment, Nucleus Accumbens drug effects, Septal Nuclei drug effects
Abstract

Life experiences, especially during critical periods of maturation, such as adolescence, can dramatically affect vulnerability to diseases at adulthood. Early exposure to positive environmental conditions such as environmental enrichment (EE) has been shown to reduce the occurrence and the intensity of neurological and psychiatric disorders including drug addiction. However, whether or not exposure to EE during early stages of life would protect from addiction when, at adulthood, individuals may find themselves in non-enriched conditions has not been investigated. Here we show that switching mice from EE to non-enriched standard environments not only results in the loss of the preventive effects of EE but also increases the rewarding effects of cocaine. This enhanced vulnerability is associated with emotional distress and with increased levels in the mRNA levels of corticotropin releasing factor (CRF) in the bed nucleus of the stria terminalis (BNST), as well as with increases in CREB phosphorylation in the BNST and in the shell of the nucleus accumbens. The increased sensitivity to the rewarding effects of cocaine is completely blocked by the CRF antagonist antalarmin, confirming a major role of the CRF system in the negative consequences of this environmental switch. These results indicate that positive life conditions during early stages of life, if they are not maintained at adulthood, may have negative emotional consequences and increase the risks to develop drug addiction.

Published
2012
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40. Design, synthesis and biological evaluation of new thalidomide analogues as TNF-α and IL-6 production inhibitors.

Author

Chaulet C, Croix C, Alagille D, Normand S, Delwail A, Favot L, Lecron JC, and Viaud-Massuard MC

Subjects
Down-Regulation, Drug Design, Humans, Leukocytes, Mononuclear drug effects, Leukocytes, Mononuclear immunology, Leukocytes, Mononuclear metabolism, Thalidomide chemical synthesis, Thalidomide pharmacology, Interleukin-6 metabolism, Thalidomide analogs & derivatives, Tumor Necrosis Factor-alpha metabolism
Abstract

Several thalidomide analogues were synthesized and compared to thalidomide and its more active analogue, lenalidomide, for their ability to inhibit the production of the pro-inflammatory cytokine tumour necrosis factor (TNF)-α and interleukin (IL)-6 by LPS-activated peripheral blood mononuclear cells (PBMCs). Among these compounds, two analogues containing sulfonyl group displayed interesting downregulation of TNF-α and IL-6 production., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Published
2011
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41. Pharmacological inhibitors of the mevalonate pathway activate pro-IL-1 processing and IL-1 release by human monocytes.

Author

Massonnet B, Normand S, Moschitz R, Delwail A, Favot L, Garcia M, Bourmeyster N, Cuisset L, Grateau G, Morel F, Silvain C, and Lecron JC

Subjects
Caspase 1 metabolism, Cell Line, Enzyme Activation drug effects, Guanosine Triphosphate metabolism, Humans, Interleukin-1beta metabolism, Lipopolysaccharides pharmacology, Monocytes drug effects, Monocytes enzymology, Phosphorylation drug effects, Protein Prenylation drug effects, Protein Transport drug effects, Simvastatin pharmacology, p38 Mitogen-Activated Protein Kinases metabolism, rac1 GTP-Binding Protein metabolism, Hydroxymethylglutaryl-CoA Reductase Inhibitors pharmacology, Interleukin-1 metabolism, Metabolic Networks and Pathways drug effects, Mevalonic Acid metabolism, Monocytes metabolism, Protein Precursors metabolism, Protein Processing, Post-Translational drug effects
Abstract

Objective: The effects of statins (3-hydroxy-3-methylglutaryl coenzyme A reductase-HMGR-inhibitors) on the inflammatory response remain unclear. HMGR is implicated in the mevalonate pathway, directly upstream of cholesterol biosynthesis. We studied the impairment by this pathway of cytokine production by peripheral blood mononuclear cells (PBMCs) and THP-1 cells. The aim was to identify a specific cytokine "signature" of cells under simvastatin treatment in order to link pharmacological inhibition of the mevalonate pathway and inflammation., Methods: Normal human PBMCs and THP-1 cells were cultured with inhibitors of HMGR (simvastatin), geranylgeranyltransferase (GGTI-298), farnesyltransferase (FTI-277), and/or caspase-1 (Z-VAD(Ome)-FMK). Following culture, cytokine production, caspase-1 activity, IL-1beta mRNA and Rac-1 activity were determined., Results: Pharmacological inhibition of the mevalonate pathway specifically enhanced the release of IL-1alpha, IL-1beta and IL-18 and inhibited IL-1ra production by LPS-activated PBMCs and THP-1 cells. Simvastatin did not modify pro-IL-1beta expression, but enhanced caspase-1 activity, the enzyme responsible for IL-1beta and IL-18 maturation. GGTI-298 also enhanced IL-1-family cytokine production, showing that geranylgeranylation is involved in caspase-1 activation. Additionally, simvastatin enhanced Rac-1 activity., Conclusion: Pharmacological inhibition of the mevalonate pathway by statins highlighted the specific induction of the proinflammatory cytokines of the IL-1 family whose maturation is either directly (i.e. IL-1beta and IL-18), or indirectly (i.e. IL-1alpha) dependant on caspase-1.

Published
2009
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42. Specific increase in caspase-1 activity and secretion of IL-1 family cytokines: a putative link between mevalonate kinase deficiency and inflammation.

Author

Normand S, Massonnet B, Delwail A, Favot L, Cuisset L, Grateau G, Morel F, Silvain C, and Lecron JC

Subjects
Animals, Disease Models, Animal, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors therapeutic use, Inflammation complications, Mevalonate Kinase Deficiency complications, Mevalonate Kinase Deficiency drug therapy, Caspase 1 metabolism, Inflammation enzymology, Inflammation immunology, Interleukin-1 metabolism, Mevalonate Kinase Deficiency enzymology, Mevalonate Kinase Deficiency immunology
Abstract

The mevalonate kinase deficiency (MKD), including hyperimmunoglobulinemia D periodic fever syndrome (HIDS) and the more severe mevalonic aciduria are rare, autosomal recessive, autoinflammatory diseases belonging to the hereditary periodic fever (HPF) family. Other members include: familial mediterranean fever (FMF), the cryopyrin-associated periodic syndromes (CAPS) and TNFR-associated periodic syndromes (TRAPS). MKD is caused by mutations in the gene encoding mevalonate kinase (MK), an enzyme of the cholesterol pathway, leading to its inactivation. The molecular mechanisms linking MKD and abnormalities of isoprenoid biosynthesis to cytokine production and inflammation have yet to be fully elucidated. Statins, which are extensively prescribed for lowering cholesterol, are potent inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase, the enzyme directly upstream of MK. In this review, we discuss recent reports demonstrating that in vitro inhibition of the mevalonate pathway by statins specifically increases the production, by activated monocytes, of cytokines of the IL-1 family, by enhancing caspase-1 activity, the enzyme responsible for IL-1beta and IL-18 maturation. The molecular mechanisms involve geranylgeranylation and the enhancement of the activity of G proteins such as Rac-1. Interestingly, activated fibroblasts from MKD patients secrete more IL-1beta than fibroblasts from healthy donors. Taken together, these data highlight the specific enhancement of the IL-1 family of cytokines, the maturation of which is caspase-1-dependent in MKD. Finally, the spectacular decrease in febrile attacks in patients with severe HIDS under IL-1 receptor antagonist (anakinra) treatment, reinforces this hypothesis. Deregulated caspase-1 activation could be responsible for the inflammatory component of MKD, thereby mechanistically linking MKD to FMF and CAPS through cytokines of the IL-1 family.

Published
2009
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43. Cytoplasmic YY1 is associated with increased smooth muscle-specific gene expression: implications for neonatal pulmonary hypertension.

Author

Favot L, Hall SM, Haworth SG, and Kemp PR

Subjects
Actins genetics, Animals, Animals, Newborn, Base Sequence, Cell Line, Cloning, Molecular, DNA Primers, Genes, myc, Mutation, Promoter Regions, Genetic, RNA, Small Interfering genetics, Swine, Transfection, Gene Expression Regulation, Hypertension, Pulmonary genetics, Muscle, Smooth, Vascular physiology, YY1 Transcription Factor physiology
Abstract

Immediately after birth the adluminal vascular SMCs of the pulmonary elastic arteries undergo transient actin cytoskeletal remodeling as well as cellular de-differentiation and proliferation. Vascular smooth muscle phenotype is regulated by serum response factor, which is itself regulated in part by the negative regulator YY1. We therefore studied the subcellular localization of YY1 in arteries of normal newborn piglets and piglets affected by neonatal pulmonary hypertension. We found that YY1 localization changed during development and that expression of gamma-smooth muscle actin correlated with expression of cytoplasmic rather than nuclear YY1. Analysis of the regulation of YY1 localization in vitro demonstrated that polymerized gamma-actin sequestered EGFP-YY1 in the cytoplasm and that YY1 activation of c-myc promoter activity was inhibited by LIM kinase, which increases actin polymerization. Consistent with these data siRNA-mediated down-regulation of YY1 in C2C12 cells increased SM22-alpha expression and inhibited cell proliferation. Thus, actin polymerization controls subcellular YY1 localization, which contributes to vascular SMC proliferation and differentiation in normal pulmonary artery development. In the absence of actin depolymerization, YY1 does not relocate to the nucleus, and this lack of relocation may contribute to the pathobiology of pulmonary hypertension.

Published
2005
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44. Overexpression of a family of RPEL proteins modifies cell shape.

Author

Favot L, Gillingwater M, Scott C, and Kemp PR

Subjects
Actins analysis, Alternative Splicing, Amino Acid Motifs genetics, Amino Acid Sequence, Animals, Cell Nucleus chemistry, Cell Nucleus metabolism, Cell Shape genetics, Cells, Cultured, Computational Biology, Gene Expression, Gene Expression Regulation, Mice, Microfilament Proteins genetics, Molecular Sequence Data, Muscle Proteins genetics, Nuclear Localization Signals genetics, Nuclear Localization Signals metabolism, Nuclear Proteins analysis, Nuclear Proteins genetics, Promoter Regions, Genetic genetics, Sequence Alignment, Tissue Distribution, Actins metabolism, Nuclear Proteins metabolism
Abstract

Proteins containing RPEL motifs (e.g., MAL) are important in the regulation of gene expression by the actin cytoskeleton. Screening the ENSEMBL database for RPEL proteins identified four additional proteins that contain RPEL motifs and nuclear localisation sequences, three of which (RPEL-A, RPEL-B and RPEL-C) are expressed in adult mouse tissues with different expression profiles. The mRNAs encoding RPEL-B and RPEL-C were subject to alternative splicing. Expression of these genes in cells indicated that they had a marked effect on cell shape. Furthermore, when expressed with a nuclear localised actin all of the different forms became restricted to the nucleus.

Published
2005
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45. Modulation of VEGF-induced endothelial cell cycle protein expression through cyclic AMP hydrolysis by PDE2 and PDE4.

Author

Favot L, Keravis T, and Lugnier C

Subjects
3',5'-Cyclic-AMP Phosphodiesterases metabolism, Carrier Proteins genetics, Cell Proliferation drug effects, Cells, Cultured, Cyclic Nucleotide Phosphodiesterases, Type 2, Cyclic Nucleotide Phosphodiesterases, Type 4, Cyclin A genetics, Cyclin D1 genetics, Cyclin-Dependent Kinase Inhibitor p21, Cyclin-Dependent Kinase Inhibitor p27, Gene Expression Regulation drug effects, Humans, Hydrolysis, Intracellular Signaling Peptides and Proteins genetics, Mitogen-Activated Protein Kinase 1 genetics, Umbilical Veins, Cell Cycle Proteins genetics, Cyclic AMP metabolism, Endothelium, Vascular cytology, Phosphoric Diester Hydrolases metabolism, Vascular Endothelial Growth Factor A pharmacology
Abstract

Endothelial cell proliferation in response to VEGF plays an important role in physiological and pathological angiogenesis. The role of PDE2 and PDE4 in VEGF-induced proliferation in HUVEC was investigated: 1) VEGF increased cAMP-hydrolytic activity by up-regulating the expression of PDE2 and PDE4 isozymes; 2) VEGF increased progression in cell cycle with an increase in p42/p44 MAP kinase, cyclin A and cyclin D1 expressions and with a decrease in p21 waf1/cip1 and p27 kip1 expressions; 3) EHNA (20 micro M), a selective PDE2 inhibitor, RP73401 (10 micro M), a selective PDE4 inhibitor blocked the VEGF-induced increase in p42/p44 MAP kinase expression; 4) RP73401, but not EHNA, blocked the VEGF-induced increase in cyclin A and decrease in p27 kip1 expressions; 5) EHNA, contrary to RP73401, enhanced the VEGF-induced increase of cyclin A and decrease of p27 kip1. 6) EHNA and RP73401 together blocked the VEGF-induced increase in cyclin D1 and decrease in p21 waf1/cip1 expressions; 7) Inhibition of VEGF-upregulated PDE2 and PDE4 reversed the VEGF-induced alterations in cell cycle protein expression, bringing back endothelial cells to a non-proliferating status. Consequently, PDE2 and PDE4 inhibitions were able to inhibit VEGF-induced endothelial cell proliferation by restoring cell cycle key protein expression, and might thus be useful in excessive angiogenesis. Furthermore, the differences between PDE2 and PDE4 effects may suggest compartmentalized effects.

Published
2004
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46. VEGF-induced HUVEC migration and proliferation are decreased by PDE2 and PDE4 inhibitors.

Author

Favot L, Keravis T, Holl V, Le Bec A, and Lugnier C

Subjects
8-Bromo Cyclic Adenosine Monophosphate pharmacology, Adenine pharmacology, Allantois blood supply, Animals, Benzamides pharmacology, Cell Cycle drug effects, Cell Division drug effects, Cell Movement drug effects, Cells, Cultured, Chick Embryo, Chorion blood supply, Cyclic AMP metabolism, Cyclic Nucleotide Phosphodiesterases, Type 2, Cyclic Nucleotide Phosphodiesterases, Type 4, Enzyme Inhibitors pharmacology, Humans, Intracellular Membranes metabolism, Neovascularization, Physiologic drug effects, Phosphodiesterase Inhibitors pharmacology, Pyridines pharmacology, Umbilical Veins, 3',5'-Cyclic-AMP Phosphodiesterases antagonists & inhibitors, Adenine analogs & derivatives, Endothelium, Vascular cytology, Endothelium, Vascular physiology, Phosphoric Diester Hydrolases drug effects, Vascular Endothelial Growth Factor A pharmacology
Abstract

Migration and proliferation of endothelial cells in response to VEGF play an important role in angiogenesis associated to pathologies such as atherosclerosis, diabetes and tumor development. Elevation of cAMP in endothelial cells has been shown to inhibit growth factor-induced proliferation. Our hypothesis was that inactivation of cAMP-specific phosphodiesterases (PDEs) would inhibit angiogenesis. The purpose of this study was to evaluate the effect of PDE inhibitors on in vitro and in vivo angiogenesis, using human umbilical vein endothelial cell (HUVEC) and chick chorioallantoic membrane (CAM) models respectively. Here, we report that: 1) PDE2, PDE3, PDE4 and PDE5 are expressed in HUVEC; 2) EHNA (20 microM), PDE2 selective inhibitor, and RP73401 (10 microM), PDE4 selective inhibitor, are able to increase the intracellular cAMP level in HUVEC; 3) EHNA and RP73401 are able to inhibit proliferation, cell cycle progression and migration of HUVEC stimulated by VEGF; 4) these in vitro effects can be mimic by treating HUVEC with the cAMP analogue, 8-Br-cAMP (600 microM); 5) only the association of EHNA and RP73401 inhibits in vivo angiogenesis, indicating that both migration and proliferation must be inhibited. These data strongly suggest that PDE2 and PDE4 represent new potential therapeutic targets in pathological angiogenesis.

Published
2003
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47. Delphinidin inhibits endothelial cell proliferation and cell cycle progression through a transient activation of ERK-1/-2.

Author

Martin S, Favot L, Matz R, Lugnier C, and Andriantsitohaina R

Subjects
Animals, Cattle, Caveolin 1, Caveolins metabolism, Cell Cycle drug effects, Cell Division drug effects, Cyclin D1 metabolism, Cyclin-Dependent Kinase Inhibitor p21, Cyclins metabolism, Down-Regulation drug effects, Endothelial Growth Factors pharmacology, Endothelium, Vascular cytology, Enzyme Activation drug effects, Immune Sera pharmacology, Intercellular Signaling Peptides and Proteins pharmacology, Lymphokines pharmacology, Mitogen-Activated Protein Kinase 1 metabolism, Mitogen-Activated Protein Kinase 3, Nitric Oxide metabolism, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factors, ras Proteins metabolism, Anthocyanins pharmacology, Endothelium, Vascular drug effects, G1 Phase drug effects, Gene Expression Regulation drug effects, Mitogen-Activated Protein Kinases metabolism, S Phase drug effects
Abstract

Epidemiological studies have shown that a diet rich in fruits and vegetables might reduce the risk of cardiovascular diseases and protect against cancer by mechanisms that have not been elucidated yet. This study was aimed to define the effect of delphinidin, a vasoactive polyphenol belonging to the class of anthocyanin, on bovine aortic endothelial cells (BAECs) proliferation. Delphinidin inhibited serum- and vascular endothelium growth factor-induced BAECs proliferation. This antiproliferative effect of delphinidin, is triggered by ERK-1/-2 activation, independent of nitric oxide pathway and is correlated with suppression of cell progression by blocking the cell cycle in G(0)/G(1) phase. Furthermore, suppression of cell cycle progression is associated with the modulation of the mitogenic signaling transduction cascade. This includes over-expression of caveolin-1 and p21(WAF1/Cip1) and down-expression of Ras and cyclin D1. In conclusion, the antiproliferative effect of delphinidin may be of importance in preventing both plaque development and stability in atherosclerosis and tumor dissemination in cancer.

Published
2003
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