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7. Radiation Adverse Outcome pathways (AOPs): examining priority questions from an international horizon-style exercise

Author

Chauhan, Vinita, primary, Beaton, Danielle, additional, Tollefsen, Knut Erik, additional, Preston, Julian, additional, Burtt, Julie J., additional, Leblanc, Julie, additional, Hamada, Nobuyuki, additional, Azzam, Edouard I., additional, Armant, Olivier, additional, Bouffler, Simon, additional, Azimzadeh, Omid, additional, Moertl, Simone, additional, Yamada, Yutaka, additional, Tanaka, Ignacia B., additional, Kaiser, Jan Christian, additional, Applegate, Kimberly, additional, Laurier, Dominique, additional, and Garnier-Laplace, Jacqueline, additional

Published
2024
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10. Citizen science in environmental health research: a comparison with conventional approaches and creation of a guidance tool issued from The LILAS initiative.

Author

LAURENT, Olivier, primary, GIRONZA, Yara CARREJO., additional, ANCELET, Sophie, additional, ARMANT, Olivier, additional, BARD, Denis, additional, BAUMGARTNER, Katia, additional, BORTOLI, Sylvie, additional, BOUDET, Céline, additional, CHAMARET, Philippe, additional, CORMIER, Stéphanie, additional, DAVID, Arthur, additional, DESQUEYROUX, Hélène, additional, GERBER, Mariette, additional, GRIMBUHLER, Sonia, additional, MOUGIN, Christian, additional, PAYRASTRE, Laurence, additional, SCHRAUB, Simon, additional, TROUSSE, Brigitte, additional, REAUD, Cynthia, additional, and CHARRON, Sylvie, additional

Published
2024
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11. Short internal open reading frames regulate the translation of N-terminally truncated proteoforms

Author

Fettig, Raphael, primary, Gonda, Zita, additional, Walter, Niklas, additional, Sallmann, Paul, additional, Thanisch, Christiane, additional, Winter, Markus, additional, Bauer, Susanne, additional, Zhang, Lei, additional, Linden, Greta, additional, Litfin, Margarethe, additional, Etard, Christelle, additional, Armant, Olivier, additional, Vazquez, Olalla, additional, and Kassel, Olivier, additional

Published
2023
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13. Editorial trend: adverse outcome pathway (AOP) and computational strategy — towards new perspectives in ecotoxicology.

Author

Baudiffier, Damien, Audouze, Karine, Armant, Olivier, Frelon, Sandrine, Charles, Sandrine, Beaudouin, Remy, Cosio, Claudia, Payrastre, Laurence, Siaussat, David, Burgeot, Thierry, Mauffret, Aourell, Degli Esposti, Davide, Mougin, Christian, Delaunay, Delphine, and Coumoul, Xavier

Subjects
ENVIRONMENTAL toxicology, ARTIFICIAL intelligence, PHARMACODYNAMICS, COMPUTATIONAL neuroscience, TOXICOLOGY, SYSTEMS biology, RISK assessment
Abstract

The adverse outcome pathway (AOP) has been conceptualized in 2010 as an analytical construct to describe a sequential chain of causal links between key events, from a molecular initiating event leading to an adverse outcome (AO), considering several levels of biological organization. An AOP aims to identify and organize available knowledge about toxic effects of chemicals and drugs, either in ecotoxicology or toxicology, and it can be helpful in both basic and applied research and serve as a decision-making tool in support of regulatory risk assessment. The AOP concept has evolved since its introduction, and recent research in toxicology, based on integrative systems biology and artificial intelligence, gave it a new dimension. This innovative in silico strategy can help to decipher mechanisms of action and AOP and offers new perspectives in AOP development. However, to date, this strategy has not yet been applied to ecotoxicology. In this context, the main objective of this short article is to discuss the relevance and feasibility of transferring this strategy to ecotoxicology. One of the challenges to be discussed is the level of organisation that is relevant to address for the AO (population/community). This strategy also offers many advantages that could be fruitful in ecotoxicology and overcome the lack of time, such as the rapid identification of data available at a time t, or the identification of "data gaps". Finally, this article proposes a step forward with suggested priority topics in ecotoxicology that could benefit from this strategy. [ABSTRACT FROM AUTHOR]

Published
2024
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15. Living Labs and other participatory approaches applied to research on multiple environnemental exposures and chronic risks

Author

LAURENT, Olivier, Yara Carrejo, Gironza, Ancelet, Sophie, Armant, Olivier, Denis, Bard, Katia, Baumgartner, Sylvie, Bortoli, Boudet, Céline, Chamaret, Philippe, Chartier, Michel, Cormier, Stéphanie, Arthur, David, Desqueyroux, Hélène, Gerber, Mariette, Gilbin, Rodolphe, Grimbuhler, Sonia, Grison, Stephane, Larqué, Lionel, Laurier, Dominique, Mougin, Christian, Gamet-Payrastre, Laurence, Rannou, Alain, Scanff, Pascale, Vanzemberg, Arnaud, Schraub, Simon, Supervil, Sylvie, Thybaud, Eric, Trousse, Brigitte, Charron, Sylvie, Laboratoire d épidémiologie des rayonnements ionisants (IRSN/PSE-SANTE/SESANE/LEPID), Service de recherche sur les effets biologiques et Sanitaires des rayonnements ionisants (IRSN/PSE-SANTE/SESANE), Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Institut de Radioprotection et de Sûreté Nucléaire (IRSN), 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 ), Laboratoire d'écotoxicologie des radionucléides (IRSN/PSE-ENV/SRTE/LECO), Service de recherche sur les transferts et les effets des radionucléides sur les écosystèmes (IRSN/PSE-ENV/SRTE), Société francophone de santé environnement (SFSE), France Nature Environnement (FNE), Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de l'Environnement Industriel et des Risques (INERIS), Institut Ecocitoyen pour la Connaissance des Pollutions [Fos-sur-Mer], Centre Permanent d'Initiatives pour l'Environnement des Pays de l'Aisne (CPIE des Pays de l'Aisne), École des Hautes Études en Santé Publique [EHESP] (EHESP), Département des sciences en santé environnementale (DEESSE), Agence de l'Environnement et de la Maîtrise de l'Energie (ADEME), Association nationale des comités et commissions locales d'information [Teteghem] (ANCCLI), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Technologies et Méthodes pour les Agricultures de demain (UMR ITAP), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Laboratoire de radiotoxicologie et radiobiologie expérimentale (IRSN/PSE-SANTE/SESANE/LRTOX), ALLISS Sciences Sociétés [Paris], Ecologie fonctionnelle et écotoxicologie des agroécosystèmes (ECOSYS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Pôle Santé Environnement - Direction Santé (IRSN/PSE-SANTE), Cellule Valorisation des données (IRSN/DTR/D3NSI/SVDDA/CVD), Direction Déléguée Développement numérique et aux systèmes d’information (IRSN/DTR/D3NSI), Ligue Nationale Contre le Cancer (LNCC), Direction des Risques et de la Performance (IRSN/DRP), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria), Service des politiques d’ouverture à la société (IRSN/DST/SPOS), Direction de la Stratégie (IRSN/DST), IRSN 2030, IS Global, and Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN)

Subjects
[SDE.ES]Environmental Sciences/Environmental and Society
Abstract

International audience; The objectives of environmental health research are diverse (e.g.: identifying situations at potential risk, estimating exposures and effects, testing the effectiveness of preventive actions) and related methods are diverse as well. Opportunities for greater implication of the civil society and related challenges differ at each step of research activities. These aspects need to be better known and shared collectively.

Published
2023

18. The LILAS project: analysis of applying participatory approaches such as Living Labs to research on multiple environmental exposures to ionizing radiation, other stressors and chronic risks

Author

LAURENT, Olivier, Yara Carrejo, Gironza, Ancelet, Sophie, Armant, Olivier, Denis, Bard, Katia, Baumgartner, Sylvie, Bortoli, Boudet, Céline, Chamaret, Philippe, Chartier, Michel, Cormier, Stéphanie, Arthur, David, Desqueyroux, Hélène, Gerber, Mariette, Gilbin, Rodolphe, Grimbuhler, Sonia, Larqué, Lionel, Laurier, Dominique, Mougin, Christian, Gamet-Payrastre, Laurence, Rannou, Alain, Reaud, Cynthia, Scanff, Pascale, Vanzemberg, Arnaud, Schraub, Simon, Supervil, Sylvie, Eric, Thybaud, Trousse, Brigitte, Charron, Sylvie, Laboratoire d épidémiologie des rayonnements ionisants (IRSN/PSE-SANTE/SESANE/LEPID), Service de recherche sur les effets biologiques et Sanitaires des rayonnements ionisants (IRSN/PSE-SANTE/SESANE), Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Institut de Radioprotection et de Sûreté Nucléaire (IRSN), 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 ), Laboratoire d'écotoxicologie des radionucléides (IRSN/PSE-ENV/SRTE/LECO), Service de recherche sur les transferts et les effets des radionucléides sur les écosystèmes (IRSN/PSE-ENV/SRTE), Société francophone de santé environnement (SFSE), France Nature Environnement (FNE), Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de l'Environnement Industriel et des Risques (INERIS), Institut Ecocitoyen pour la Connaissance des Pollutions [Fos-sur-Mer], Centre Permanent d'Initiatives pour l'Environnement des Pays de l'Aisne (CPIE des Pays de l'Aisne), École des Hautes Études en Santé Publique [EHESP] (EHESP), Agence de l'Environnement et de la Maîtrise de l'Energie (ADEME), Association nationale des comités et commissions locales d'information [Teteghem] (ANCCLI), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Technologies et Méthodes pour les Agricultures de demain (UMR ITAP), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), ALLISS Sciences Sociétés [Paris], Ecologie fonctionnelle et écotoxicologie des agroécosystèmes (ECOSYS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Pôle Santé Environnement - Direction Santé (IRSN/PSE-SANTE), Service des politiques d’ouverture à la société (IRSN/DST/SPOS), Direction de la Stratégie (IRSN/DST), Cellule Valorisation des données (IRSN/DTR/D3NSI/SVDDA/CVD), Direction Déléguée Développement numérique et aux systèmes d’information (IRSN/DTR/D3NSI), Service de la programmation, des partenariats, de la prospective et de l’appui à l’innovation (IRSN/DST/SP3IN), Ligue Nationale Contre le Cancer (LNCC), Direction des Risques et de la Performance (IRSN/DRP), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria), IRSN2030, ICRP - International Commission on Radiation Protection, Université de Rennes (UR), Département des sciences en santé environnementale (DEESSE), Laboratoire d'étude et de recherche en environnement et santé (LERES), Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Protection et Sûreté Nucléaire (IPSN), Laboratoire de radiotoxicologie et radiobiologie expérimentale (IRSN/PRP-HOM/SRBE/LRTOX), Laboratoire de radiotoxicologie et radiobiologie expérimentale (IRSN/PSE-SANTE/SESANE/LRTOX), IRSN via appel à projets interne IRSN2030, TECNICO LISBOA, and Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan)

Subjects
[SDE]Environmental Sciences, [SDE.ES]Environmental Sciences/Environmental and Society
Abstract

International audience; Participatory research approaches in environmental health are still rarely applied to radiation research. Opportunities for greater implication of the civil society and related challenges differ at each step of such research activities. The LILAS project aimed, as a preparatory step toward the development of participatory research projects on multiple environmental exposures to ionizing radiation and other stressors

Published
2022

19. Radiation adverse outcome pathways (AOPs) are on the horizon: advancing radiation protection through an international Horizon-Style exercise

Author

Burtt, Julie J., primary, Leblanc, Julie, additional, Randhawa, Kristi, additional, Ivanova, Addie, additional, Rudd, Murray A., additional, Wilkins, Ruth, additional, Azzam, Edouard I., additional, Hecker, Markus, additional, Horemans, Nele, additional, Vandenhove, Hildegarde, additional, Adam-Guillermin, Christelle, additional, Armant, Olivier, additional, Klokov, Dmitry, additional, Audouze, Karine, additional, Kaiser, Jan Christian, additional, Moertl, Simone, additional, Lumniczky, Katalin, additional, Tanaka, Ignacia B., additional, Yamada, Yutaka, additional, Hamada, Nobuyuki, additional, Al-Nabulsi, Isaf, additional, Preston, R. Julian, additional, Bouffler, Simon, additional, Applegate, Kimberly, additional, Cool, Donald, additional, Beaton, Danielle, additional, Tollefsen, Knut Erik, additional, Garnier-Laplace, Jacqueline, additional, Laurier, Dominique, additional, and Chauhan, Vinita, additional

Published
2022
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21. Development of an adverse outcome pathway for radiation-induced microcephaly via expert consultation and machine learning

Author

Jaylet, Thomas, primary, Quintens, Roel, additional, Benotmane, Mohamed Abderrafi, additional, Luukkonen, Jukka, additional, Tanaka, Ignacia Braga, additional, Ibanez, Chrystelle, additional, Durand, Christelle, additional, Sachana, Magdalini, additional, Azimzadeh, Omid, additional, Adam-Guillermin, Christelle, additional, Tollefsen, Knut Erik, additional, Laurent, Olivier, additional, Audouze, Karine, additional, and Armant, Olivier, additional

Published
2022
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22. Radiological and chemical exposures and risks of cancer in the Constances cohort (COREXCA)

Author

LAURENT, Olivier, Renaud, Philippe, Broggio, David, Blanchardon, Eric, Dreuil, Serge, Greau, Claire, Vignaud, Caroline, Ancelet, Sophie, Armant, Olivier, Bernier, Marie-Odile, Clero, Enora, Durand, Christelle, Ebrahimian Chiusa, Teni, Foucault, Anais, Goldberg, Marcel, Guerin, Sabine, Huet, Christelle, Lequy, Emeline, Métivier, Jean-Michel, Grison, Stephane, Ibanez, Chrystelle, Ielsch, Géraldine, Klokov, Dmitry, Monceau, V., Roy, Herve, guihenneuc, chantal, Leuraud, Klervi, Nathalie, Velly, Zins, Marie, Laboratoire d épidémiologie des rayonnements ionisants (IRSN/PSE-SANTE/SESANE/LEPID), Service de recherche sur les effets biologiques et Sanitaires des rayonnements ionisants (IRSN/PSE-SANTE/SESANE), Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Pôle Santé Environnement- Direction Environnement (IRSN/PSE-ENV), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Laboratoire d'évaluation de la dose interne (IRSN/PSE-SANTE/SDOS/LEDI), Service de dosimétrie (IRSN/PSE-SANTE/SDOS), Bureau d'expertise en radioprotection de la population (IRSN/PSE-ENV/SEREN/BERAP), Service d'expertise et d'étude en radioprotection des populations et de la radioactivité dans l'environnement (IRSN/PSE-ENV/SEREN), Unité d'expertise en radioprotection médicale (IRSN/PSE-SANTE/SER/UEM), Service d'études et d'expertise en radioprotection (IRSN/PSE-SANTE/SER), Bureau d'étude et d'expertise du radon (IRSN/PSE-ENV/SEREN/BERAD), Laboratoire d'écotoxicologie des radionucléides (IRSN/PSE-ENV/SRTE/LECO), Service de recherche sur les transferts et les effets des radionucléides sur les écosystèmes (IRSN/PSE-ENV/SRTE), Laboratoire de radiotoxicologie et radiobiologie expérimentale (IRSN/PSE-SANTE/SESANE/LRTOX), Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Institut National de l'Environnement Industriel et des Risques (INERIS), Laboratoire de dosimétrie des rayonnements ionisants (IRSN/PSE-SANTE/SDOS/LDRI), Laboratoire d'étude et d'expertise sur la radioactivité de l'environnement (IRSN/PSE-ENV/SEREN/LEREN), Bureau d'analyse et de suivi des expositions professionnelles (IRSN/PSE-SANTE/SER/BASEP), Biostatistique, traitement et modélisation des données biologiques = Biostatistic, Biological Data treatment and Modelisation (BioSTM - URP_7537), Université Paris Cité (UPCité), Fondation de France (grant WB-2020-29711) French Agency for Food, Environmental and Occupational Health & Safety (ANSES, grant EST-21-188), European Radiation Protection Week, and European Project: 900009,RadoNorm

Subjects
[SDV]Life Sciences [q-bio]
Abstract

International audience

Published
2022

24. Le projet LILAS : analyse de l’application des approches participatives sur les multi-expositions environnementales et les risques chroniques

Author

Laurent, Olivier, Carrejo Gironza, Yara, Ancelet, Sophie, Armant, Olivier, Bard, Denis, Baumgartner, Katia, Bortoli, Sylvie, Boudet, Céline, Chamaret, Philippe, Chartier, Michel, Cormier, Stéphanie, David, Arthur, Desqueyroux, Hélène, Gerber, Mariette, Gilbin, Rodolphe, Grimbuhler, Sonia, Grison, Stephane, Larqué, Lionel, Laurier, Dominique, Mougin, Christian, Gamet-Payrastre, Laurence, Rannou, Alain, Vanzemberg, Arnaud, Schraub, Simon, Supervil, Sylvie, Thybaud, Eric, Trousse, Brigitte, Charron, Sylvie, Laboratoire d épidémiologie des rayonnements ionisants (IRSN/PSE-SANTE/SESANE/LEPID), Service de recherche sur les effets biologiques et Sanitaires des rayonnements ionisants (IRSN/PSE-SANTE/SESANE), Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Laboratoire d'écotoxicologie des radionucléides (IRSN/PSE-ENV/SRTE/LECO), Service de recherche sur les transferts et les effets des radionucléides sur les écosystèmes (IRSN/PSE-ENV/SRTE), Société francophone de santé environnement (SFSE), France Nature Environnement (FNE), Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut National de l'Environnement Industriel et des Risques (INERIS), Institut Ecocitoyen pour la Connaissance des Pollutions [Fos-sur-Mer], Service d'expertise et d'étude en radioprotection des populations et de la radioactivité dans l'environnement (IRSN/PSE-ENV/SEREN), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Centre Permanent d'Initiatives pour l'Environnement des Pays de l'Aisne (CPIE des Pays de l'Aisne), EHESP-Irset (EHESP-Irset), École des Hautes Études en Santé Publique [EHESP] (EHESP), Agence de l'Environnement et de la Maîtrise de l'Energie (ADEME), Association nationale des comités et commissions locales d'information [Teteghem] (ANCCLI), Technologies et Méthodes pour les Agricultures de demain (UMR ITAP), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro Montpellier, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Alliance Sciences-Société, Ecologie fonctionnelle et écotoxicologie des agroécosystèmes (ECOSYS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Pôle Santé Environnement - Direction Santé (IRSN/PSE-SANTE), Service des politiques d’ouverture à la société (IRSN/DST/SPOS), Direction de la Stratégie (IRSN/DST), Service de la programmation, des partenariats, de la prospective et de l’appui à l’innovation (IRSN/DST/SP3IN), Ligue Nationale Contre le Cancer (LNCC), Direction des Risques et de la Performance (IRSN/DRP), Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria), IRSN2030, Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Laboratoire d'écotoxicologie des radionucléides (IRSN/PRP-ENV/SERIS/LECO), Service de Recherche et d'Expertise sur les Risques environnementaux (IRSN/PRP-ENV/SERIS), Institut National de la Santé et de la Recherche Médicale (INSERM), 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 ), Département des sciences en santé environnementale (DEESSE), Information – Technologies – Analyse Environnementale – Procédés Agricoles (UMR ITAP), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, Laboratoire de radiotoxicologie et radiobiologie expérimentale (IRSN/PSE-SANTE/SESANE/LRTOX), ALLISS Sciences Sociétés [Paris], and Ligue Nationale Contre le Cancer - Paris

Subjects
méthodes en santé-environ- multiple exposure, Laboratoire viavant, Méthodes en santé-environnement, multi-expositions, Methods in environmental health research, Analysis tools, co-construction, Multiple exposures, analysis tool, [SDE]Environmental Sciences, participatory research, Living Lab, Grille d'analyse, methods in environmental health, recherches participatives
Abstract

International audience; Context: Participatory research in environmental health remains rare in France. The objectives of environmental health research projects can, like their methods, be very diverse. Opportunities for greater involvement of civil society, as well as its challenges, differ at each step of such research activities. All these aspects need to be widely shared. As a preparatory step toward the development of concrete new participatory research projects on multiple environmental exposures, the LILAS project aimed to (1) favor the mutual understanding of the main issues and research methods in environmental health and their stakes for different participants, but also the requirements, strengths, and limitations of these methods, and (2) identify the expected benefits and points to watch out for related to stronger civic participation in these projects.Methods: The LILAS project identified and gathered together institutional researchers, academics and civil society participants (mainly from nongovernmental organizations) interested in multiple exposures (chemical and radiological). The relevant literature was searched to learn from previous participatory research projects in this broad field. Several meetings enabled the group to collectively identify different types of studies and analyze the benefits, limitations and methods related to the introduction of such participation. An analysis matrix was co-constructed and completed by study participants, as in a Living Lab approach.Results: The matrix lists for different types of studies (assessment of environmental exposures, identification of their determinants, interventions on these exposures, quantitative risk assessment, epidemiological studies, experimental research, ecosystem health, etc.) the expected benefits for several categories of stakeholders, the fundamental principles of research methods, and their related practical constraints, advantages and limitations related to the use of participatory or more standard approaches.Conclusion: The LILAS project enabled the development of a solid basis for the co-construction of participatory research projects to study multiple environmental exposures.; Contexte : Les recherches participatives en santé-environnement restent encore peu développées en France. Les objectifs poursuivis par les recherches en santé-environnement (par exemple : estimer des expositions et/ou des effets, tester des actions préventives) et les méthodes employées à ces fins sont variées. Les opportunités d’une plus grande implication de la société civile et les défis associés diffèrent à chaque étape de ces recherches. Ces aspects demandent à être mieux appréhendés collectivement. Le projet LILAS visait, en amont du développement de futurs projets concrets de recherches participatives sur les multi-expositions environnementales, à (1) favoriser une bonne compréhension commune des principales problématiques et méthodes de recherche en santé-environnement, de leurs enjeux, prérequis, forces et limites, et à (2) identifier les bénéfices et points de vigilance liés à l’introduction de plus fortes dimensions participatives dans ces recherches.Méthode adoptée : Le projet LILAS a identifié et rassemblé des chercheurs institutionnels, académiques et acteurs de la société civile (associations loi 1901) intéressés par les multi-expositions (chimiques, radiologiques). Cinq réunions ont permis d’identifier collectivement différents types d’études et de réfléchir sur les apports, limites et prérequis méthodologiques relatifs à l’introduction de différents degrés de participation dans celles-ci. Une matrice résumant ces aspects a été co-construite puis alimentée par les participants, en s’inspirant des approches Living Lab (soit laboratoire vivant).Résultats : Pour différents types d’études (études d’estimations d’expositions, d’interventions sur celles-ci, évaluations de risques sanitaires, études épidémiologiques, expérimentales, études sur la santé des écosystèmes, etc.), la matrice élaborée en commun liste les bénéfices attendus pour différentes parties prenantes, les principes fondamentaux des méthodes employées et contraintes pratiques associées, les avantages et limites relatifs à l’emploi d’approches participatives (notamment les Living Labs) ou plus « classiques ».Conclusion : Le projet LILAS a permis de poser des bases consolidées pour la co-construction de projets de recherches participatives sur les multi-expositions environnementales.

Published
2022

25. Radiological component of the Exposome, multiple exposures, risks of cancer and other chronic diseases in the Constances cohort (CORALE)

Author

LAURENT, Olivier, Renaud, Philippe, Dreuil, Serge, Greau, Claire, Vignaud, Caroline, Ancelet, Sophie, Armant, Olivier, Bernier, Marie-Odile, Clero, Enora, Durand, Christelle, Ebrahimian Chiusa, Teni, Goldberg, Marcel, Lequy, Emeline, Grison, Stephane, Ibanez, Chrystelle, Ielsch, Géraldine, Klokov, Dmitry, Monceau, V., Roy, Herve, Guihenneuc, Chantal, Leuraud, Klervi, Zins., Marie, Laboratoire d épidémiologie des rayonnements ionisants (IRSN/PSE-SANTE/SESANE/LEPID), Service de recherche sur les effets biologiques et Sanitaires des rayonnements ionisants (IRSN/PSE-SANTE/SESANE), Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Pôle Santé Environnement- Direction Environnement (IRSN/PSE-ENV), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Unité d'expertise en radioprotection médicale (IRSN/PSE-SANTE/SER/UEM), Service d'études et d'expertise en radioprotection (IRSN/PSE-SANTE/SER), Bureau d'étude et d'expertise du radon (IRSN/PSE-ENV/SEREN/BERAD), Service d'expertise et d'étude en radioprotection des populations et de la radioactivité dans l'environnement (IRSN/PSE-ENV/SEREN), Laboratoire d'écotoxicologie des radionucléides (IRSN/PSE-ENV/SRTE/LECO), Service de recherche sur les transferts et les effets des radionucléides sur les écosystèmes (IRSN/PSE-ENV/SRTE), Laboratoire de radiotoxicologie et radiobiologie expérimentale (IRSN/PSE-SANTE/SESANE/LRTOX), Cohortes épidémiologiques en population (CONSTANCES), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay-Université Paris Cité (UPCité), Bureau d'analyse et de suivi des expositions professionnelles (IRSN/PSE-SANTE/SER/BASEP), Biostatistique, traitement et modélisation des données biologiques = Biostatistic, Biological Data treatment and Modelisation (BioSTM - URP_7537), Université Paris Cité (UPCité), Fondation de France, Radonorm, and European Project: 900009,RadoNorm

Subjects
[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie
Abstract

International audience; ContextThe whole population is exposed throughout its life to ionizing radiation (IR) at varying levels, via multiple natural and artificial sources, whether in the context of the residential environment, various activities (professional or other such as air travel) or for medical reasons (diagnostic or therapeutic procedures). The carcinogenic effects of IR are well documented at dose levels of 100 milliGrays (mGy) or higher. There is still controversy about the shape of the relationships between exposure and cancer risks at lower doses, called “low doses”. In addition, quantification of the effects of multi-exposure to IR and other cancer risk factors is poorly documented, with the exception of the interaction between tobacco and radon on lung cancer risk. Similarly, the relationships between exposures to IR at different stages of life (e.g., during childhood, puberty, etc.) and late health effects remain poorly characterized. Potential associations between low doses of IR and non-cancer chronic diseases also require better documentation. ObjectivesThe first objective of the CORALE project is to carry out the broadest possible reconstruction of doses of IR from environmental sources (radon, terrestrial and cosmic radiation, food, nuclear installations and other artificial sources), medical (diagnostic and therapeutic procedures) and occupational (nuclear workers but also other industries using radioactive sources, health professionals… ) received by participants in the Constances cohort since birth, following the logic of the exposome concept (for its radiological component). The second objective will be to estimate the risks of cancers and other chronic diseases potentially associated with the cumulative doses received (from several sources of IR and over time) taking into account the potential influence of the context of multi-exposures to other risk factors.MethodsIn order to reconstruct the annual doses due to radioactivity of natural and artificial origin received by each member of the Constances cohort since their birth, a large number of sources of radioactivity must be considered. Reconstructions related to environmental, medical and occupational exposures will be performed by different units of the IRSN in collaboration with the Constances cohort team. To do this, a questionnaire will be sent to cohort members who have already provided their residential histories. The statistical analyses (e.g., Cox models with time-dependent covariates) will be carried out at the IRSN epidemiology laboratory and will benefit from the expertise of radiobiologists, supporting the exploration of specific hypotheses and interpretations. The use of innovative regression methods on exposure profiles will be explored in collaboration with the University of Paris.PerspectivesCORALE is part of a broader long-term research programme, which will include the effects of other multi-exposures (e.g., IR and other environmental exposures) and the study of risk and exposure biomarkers through the Constances biobank, further complementing the application of the exposome concept through the study of within-body regulations following exposures. This program will help improve the characterization of the exposome and its relation with chronic diseases in the Constances cohort.

Published
2021

26. Unusual evolution of tree frog populations in the Chernobyl exclusion zone

Author

Car, Clément, primary, Gilles, André, additional, Armant, Olivier, additional, Burraco, Pablo, additional, Beaugelin‐Seiller, Karine, additional, Gashchak, Sergey, additional, Camilleri, Virginie, additional, Cavalié, Isabelle, additional, Laloi, Patrick, additional, Adam‐Guillermin, Christelle, additional, Orizaola, Germán, additional, and Bonzom, Jean‐Marc, additional

Published
2022
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28. Living Labs and other participatory approaches applied to research on multiple environnemental exposures and chronic risks

Author

Laurent, Olivier, primary, Carrejo Gironza, Yara, additional, Ancelet, Sophie, additional, Armant, Olivier, additional, Bard, Denis, additional, Baumgartner, Katia, additional, Bortoli, Sylvie, additional, Boudet, Céline, additional, Chamaret, Philippe, additional, Trousse, Brigitte, additional, David, Arthur, additional, Desqueyroux, Hélène, additional, Gerber, Mariette, additional, Gilbin, Rodolphe, additional, Grimbuhler, Sonia, additional, Grison, Stéphane, additional, Larqué, Lionel, additional, Mougin, Christian, additional, Payrastre, Laurence, additional, Platel, Sylvie, additional, Rannou, Alain, additional, Vanzemberg, Arnaud, additional, Schraub, Simon, additional, Cormier, Stéphanie, additional, and Charron, Sylvie, additional

Published
2021
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29. Two independent transcription initiation codes overlap on vertebrate core promoters

Author

Haberle, Vanja, Li, Nan, Hadzhiev, Yavor, Plessy, Charles, Previti, Christopher, Nepal, Chirag, Gehrig, Jochen, Dong, Xianjun, Akalin, Altuna, Suzuki, Ana Maria, van IJcken, Wilfred F.J., Armant, Olivier, Ferg, Marco, Strahle, Uwe, Carninci, Piero, Muller, Ferenc, and Lenhard, Boris

Subjects
Genetic research, Promoters (Genetics) -- Research, Genetic code -- Research, Genetic transcription -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

A core promoter is a stretch of DNA surrounding the transcription start site (TSS) that integrates regulatory inputs (1) and recruits general transcription factors to initiate transcription (2). The nature and causative relationship of the DNA sequence and chromatin signals that govern the selection of most TSSs by RNA polymerase II remain unresolved. Maternal to zygotic transition represents the most marked change of the transcriptome repertoire in the vertebrate life cycle (3-6). Early embryonic development in zebrafish is characterized by a series of transcriptionally silent cell cycles regulated by inherited maternal gene products: zygotic genome activation commences at the tenth cell cycle, marking the mid-blastula transition (7). This transition provides a unique opportunity to study the rules of TSS selection and the hierarchy of events linking transcription initiation with key chromatin modifications. We analysed TSS usage during zebrafish early embryonic development at high resolution using cap analysis of gene expression (8), and determined the positions of H3K4me3-marked promoter-associated nucleosomes (9). Here we show that the transition from the maternal to zygotic transcriptome is characterized by a switch between two fundamentally different modes of defining transcription initiation, which drive the dynamic change of TSS usage and promoter shape. A maternal-specific TSS selection, which requires an A/T-rich (W-box) motif, is replaced with a zygotic TSS selection grammar characterized by broader patterns of dinucleotide enrichments, precisely aligned with the first downstream (11) nucleosome. The developmental dynamics of the H3K4me3-marked nucleosomes reveal their DNA-sequence-associated positioning at promoters before zygotic transcription and subsequent transcription-independent adjustment to the final position downstream of the zygotic TSS. The two TSS-defining grammars coexist, often physically overlapping, in core promoters of constitutively expressed genes to enable their expression in the two regulatory environments. The dissection of overlapping core promoter determinants represents a framework for future studies of promoter structure and function across different regulatory contexts., Mapping of TSSs using cap analysis of gene expression (CAGE) (8) identified two major promoter classes with respect to TSS precision (10,11): 'sharp' promoters with one predominant TSS, often associated [...]

Published
2014

34. Le projet LILAS : Living Labs et autres approches participatives appliquées à la recherche sur les multi-expositions environnementales et les risques chroniques

Author

Laurent, Olivier, Gironza, Yara Carrejo, Ancelet, Sophie, Armant, Olivier, Bard, Denis, Baumgartner, Katia, Bortoli, Sylvie, Boudet, Céline, Chamaret, Philippe, Chartier, Michel, Cormier, Stéphanie, David, Arthur, Desqueyroux, Hélène, Gerber, Mariette, Gilbin, Rodolphe, Grimbuhler, Sonia, Grison, Stéphane, Larqué, Lionel, Laurier, Dominique, Mougin, Christian, Gamet-Payrastre, Laurence, Platel, Sylvie, Rannou, Alain, Scanff, Pascale, Vanzemberg, Arnaud, Schraub, Simon, Supervil, Sylvie, Thybaud, Eric, Trousse, Brigitte, Charron, Sylvie, PSE-SANTE/SESANE/LEPID, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), PSE-ENV/SRTE/LECO, Société francophone de santé environnement (SFSE), France Nature Environnement (FNE), Toxicité environnementale, cibles thérapeutiques, signalisation cellulaire (T3S - UMR_S 1124), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut National de l'Environnement Industriel et des Risques (INERIS), Institut Ecocitoyen pour la Connaissance des Pollutions [Fos-sur-Mer], PSE-ENV/SEREN, CPIE des Pays de l'Aisne, EHESP-Irset (EHESP-Irset), École des Hautes Études en Santé Publique [EHESP] (EHESP), Agence de l'Environnement et de la Maîtrise de l'Energie (ADEME), ANCCLI, PSE-ENV/SRTE, Information – Technologies – Analyse Environnementale – Procédés Agricoles (UMR ITAP), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), PSE-SANTE/SESANE/LRTOX, ALLISS Sciences Sociétés [Paris], PSE-SANTE/SESANE, Ecologie fonctionnelle et écotoxicologie des agroécosystèmes (ECOSYS), AgroParisTech-Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), PSE-SANTE, DTR/D3NSI/SVDDA, DST/SP3In, Ligue Nationale Contre le Cancer - Paris, Ligue Nationnale Contre le Cancer, DRP, Inria Sophia Antipolis - Méditerranée (CRISAM), Institut National de Recherche en Informatique et en Automatique (Inria), DST/SPOS, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Institut National de la Santé et de la Recherche Médicale (INSERM)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Université d'Angers (UA), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire d épidémiologie des rayonnements ionisants (IRSN/PSE-SANTE/SESANE/LEPID), Service de recherche sur les effets biologiques et Sanitaires des rayonnements ionisants (IRSN/PSE-SANTE/SESANE), Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Institut de Radioprotection et de Sûreté Nucléaire (IRSN), 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 ), Laboratoire d'écotoxicologie des radionucléides (IRSN/PSE-ENV/SRTE/LECO), Service de recherche sur les transferts et les effets des radionucléides sur les écosystèmes (IRSN/PSE-ENV/SRTE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Service d'expertise et d'étude en radioprotection des populations et de la radioactivité dans l'environnement (IRSN/PSE-ENV/SEREN), Laboratoire d'étude et de recherche en environnement et santé (LERES), Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut Agro - Montpellier SupAgro, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Laboratoire de radiotoxicologie et radiobiologie expérimentale (IRSN/PSE-SANTE/SESANE/LRTOX), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Pôle Santé Environnement - Direction Santé (IRSN/PSE-SANTE), Service Valorisation des Données et Développement des Applications (IRSN/DTR/D3NSI/SVDDA), Direction Déléguée Développement numérique et aux systèmes d’information (IRSN/DTR/D3NSI), Service de la programmation, des partenariats, de la prospective et de l’appui à l’innovation (IRSN/DST/SP3IN), Direction de la Stratégie (IRSN/DST), Ligue Nationale Contre le Cancer (LNCC), Direction des Risques et de la Performance (IRSN/DRP), Service des politiques d’ouverture à la société (IRSN/DST/SPOS), Trousse, Brigitte, and Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan)

Subjects
[SDV] Life Sciences [q-bio], méthodes, [SHS.STAT]Humanities and Social Sciences/Methods and statistics, [SDV]Life Sciences [q-bio], [SHS.STAT] Humanities and Social Sciences/Methods and statistics, santé environnementale, sciences participatives, [SDE.ES] Environmental Sciences/Environmental and Society, Multi-expositions, co-construction, [SDE.ES]Environmental Sciences/Environmental and Society
Abstract

National audience; Contexte :Les sciences participatives en santé environnementale restent peu développées en France. Les objectifs poursuivis par les recherches en santé environnement (ex: estimer des expositions, évaluer des risques, tester des actions préventives) et méthodes employées sont variés. Les opportunités de plus grandes implications de la société civile et défis associés peuvent également différer à chaque étape de ces recherches. Ces aspects demandent à être mieux appréhendés collectivement. LILAS vise, en amont du développement de futurs projets de recherches participatives sur les multi-expositions environnementales, à 1) co-construire, entre chercheurs institutionnels et représentants de la société civile, une bonne compréhension commune des principales problématiques et méthodes de recherche en santé environnementale, de leurs enjeux, prérequis, forces et limites 2) identifier les bénéfices et points de vigilance liés à l’introduction de plus fortes dimensions participatives dans ces recherches. Méthode :LILAS a rassemblé une vingtaine de chercheurs institutionnels, académiques et représentants de la société civile intéressés par de multiples expositions environnementales (chimiques, radiologiques). Une recherche bibliographique a été initiée pour tirer le retour d’expérience de projets de sciences participatives à l’international. Plusieurs réunions ont permis d’identifier collectivement différents types d’études et de réfléchir sur les apports, limites et précautions méthodologiques relatifs à l’introduction de différents degrés de participation dans celles-ci. Une matrice d’analyse a été co-construite puis alimentée par les participants.Résultats :Pour différents types d’études (évaluations d’expositions multiples, identification de déterminants, tests d’interventions, développement de capteurs et applications, évaluations de risques sanitaires, études épidémiologiques, recherches expérimentales, études sur la santé des écosystèmes…), la matrice liste les bénéfices attendus pour différentes catégories de parties prenantes, les conditions méthodologiques (ex : contrôle des biais, puissance statistique) et contraintes associées, les avantages et limites relatives à l’emploi d’approches participatives ou plus “classiques”.Conclusion :LILAS a permis, par acculturation croisée, de poser des bases consolidées pour la co-construction de futurs projets de recherches participatives sur les multi-expositions environnementales.

Published
2020

35. Étude des effets d'une exposition aux rayonnements ionisants sur le développement du poisson zèbre par une approche de biologie des systèmes

Author

ARMANT, Olivier, PSE-ENV/SRTE/LECO, and Institut de Radioprotection et de Sûreté Nucléaire (IRSN)

Subjects
[SDV]Life Sciences [q-bio]
Abstract

International audience; Embryonic development is particularly vulnerable to stress and DNA damage, as mutations can accumulate through cell proliferation in a wide number of cells and organs. However, the biological effects of chronic exposure to ionising radiation (IR) at low and moderate dose rates (< 6 mGy/h) remain largely controversial, raising concerns for environmental protection. We employed a systems biology approach involving, transcriptomics and epigenetics to understand how exposures to low to moderate dose rates of IR impact embryonic development, using zebrafish as a model. Our data highlight that the transcriptional program regulating morphogenesis in gastrulating embryos was modified at dose rates greater than or equal to 0.5 mGy/h, which might predict potential neurogenesis and somitogenesis defects observed at similar dose rates later in development. In particular we observed that the retinoic acid pathway was impaired during gastrulation and after organogenesis, and might thus constitute a key event in the progression of the adverse outcomes induced by RI. Future studies will employ functional studies to better characterize the implication of the retinoic acid pathway.

Published
2020

37. Neurogenin 2 controls cortical neuron migration through regulation of Rnd2

Author

Heng, Julian Ik-Tsen, Nguyen, Laurent, Castro, Diogo S., Zimmer, Celine, Wildner, Hendrik, Armant, Olivier, Skowronska-Krawczyk, Dorota, Bedogni, Francesco, Matter, Jean-Marc, Hevner, Robert, and Guillemot, Francois

Subjects
Cerebral cortex -- Research -- Physiological aspects, Binding proteins -- Research -- Physiological aspects, Neurons -- Research -- Physiological aspects, Cell migration -- Research -- Physiological aspects, Environmental issues, Science and technology, Zoology and wildlife conservation, Physiological aspects, Research
Abstract

Motility is a universal property of newly generated neurons. How cell migration is coordinately regulated with other aspects of neuron production is not well understood. Here we show that the [...]

Published
2008

39. Unusual evolution of tree frog populations in the Chernobyl exclusion zone

Author

Car, Clément, primary, Gilles, André, additional, Armant, Olivier, additional, Burraco, Pablo, additional, Beaugelin-Seiller, Karine, additional, Gashchak, Sergey, additional, Camilleri, Virginie, additional, Cavalie, Isabelle, additional, Laloi, Patrick, additional, Adam-Guillermin, Christelle, additional, Orizaola, Germán, additional, and Bonzom, Jean-Marc, additional

Published
2020
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40. Ionising Radiation Induces Promoter DNA Hypomethylation and Perturbs Transcriptional Activity of Genes Involved in Morphogenesis during Gastrulation in Zebrafish

Author

Murat El Houdigui, Sophia, Adam-Guillermin, Christelle, ARMANT, Olivier, PSE-ENV/SRTE/LECO, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), and PSE-SANTE/SDOS/LMDN

Subjects
Transcriptional Activation, animal structures, [SDV]Life Sciences [q-bio], Organogenesis, Article, lcsh:Chemistry, Mesoderm, transcriptomics, Radiation, Ionizing, Ectoderm, Morphogenesis, Animals, gastrulation, Promoter Regions, Genetic, germ layer, lcsh:QH301-705.5, AOP, development, DNA methylation, ionising radiation, Gene Expression Profiling, Computational Biology, Gene Expression Regulation, Developmental, zebrafish, lcsh:Biology (General), lcsh:QD1-999, embryonic structures, Transcriptome, epigenetic
Abstract

Embryonic development is particularly vulnerable to stress and DNA damage, as mutations can accumulate through cell proliferation in a wide number of cells and organs. However, the biological effects of chronic exposure to ionising radiation (IR) at low and moderate dose rates (&lt, 6 mGy/h) remain largely controversial, raising concerns for environmental protection. The present study focuses on the molecular effects of IR (0.005 to 50 mGy/h) on zebrafish embryos at the gastrula stage (6 hpf), at both the transcriptomics and epigenetics levels. Our results show that exposure to IR modifies the expression of genes involved in mitochondrial activity from 0.5 to 50 mGy/h. In addition, important developmental pathways, namely, the Notch, retinoic acid, BMP and Wnt signalling pathways, were altered at 5 and 50 mGy/h. Transcriptional changes of genes involved in the morphogenesis of the ectoderm and mesoderm were detected at all dose rates, but were prominent from 0.5 to 50 mGy/h. At the epigenetic level, exposure to IR induced a hypomethylation of DNA in the promoter of genes that colocalised with both H3K27me3 and H3Kme4 histone marks and correlated with changes in transcriptional activity. Finally, pathway enrichment analysis demonstrated that the DNA methylation changes occurred in the promoter of important developmental genes, including morphogenesis of the ectoderm and mesoderm. Together, these results show that the transcriptional program regulating morphogenesis in gastrulating embryos was modified at dose rates greater than or equal to 0.5 mGy/h, which might predict potential neurogenesis and somitogenesis defects observed at similar dose rates later in development.

Published
2020

41. A systems biology approach reveals neuronal and muscle developmental defects after chronic exposure to ionising radiation in zebrafish

Author

Murat El Houdigui, Sophia, Adam-Guillermin, Christelle, Loro, Giovanna, Arcanjo, Caroline, Frelon, Sandrine, Floriani, Magali, Dubourg, Nicolas, Baudelet, Emilie, Audebert, Stéphane, Camoin, Luc, Armant, Olivier, PSE-ENV/SRTE/LECO, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PSE-SANTE/SDOS/LMDN, Centre de Recherche en Cancérologie de Marseille (CRCM), Aix Marseille Université (AMU)-Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Fédération nationale des Centres de lutte contre le Cancer (FNCLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Luc, Camoin, Laboratoire d'écotoxicologie des radionucléides (IRSN/PSE-ENV/SRTE/LECO), Service de recherche sur les transferts et les effets des radionucléides sur les écosystèmes (IRSN/PSE-ENV/SRTE), Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Laboratoire de micro-irradiation, de métrologie et de dosimétrie neutrons (IRSN/PSE-SANTE/SDOS/LMDN), and Service de dosimétrie (IRSN/PSE-SANTE/SDOS)

Subjects
[SDV]Life Sciences [q-bio], Systems analysis, Embryonic Development, lcsh:Medicine, Antineoplastic Agents, Tretinoin, Muscle Development, Nervous System, Article, Radiation, Ionizing, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Transcriptomics, lcsh:Science, Zebrafish, [SDV.EE]Life Sciences [q-bio]/Ecology, environment, Muscles, Systems Biology, lcsh:R, Zebrafish Proteins, [SDV] Life Sciences [q-bio], [SDV.EE] Life Sciences [q-bio]/Ecology, environment, Larva, Embryogenesis, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], lcsh:Q, Transcriptome, Transcription Factors
Abstract

International audience; contamination of the environment after the chernobyl and fukushima Daiichi nuclear power plant (npp) disasters led to the exposure of a large number of humans and wild animals to radioactive substances. However, the sub-lethal consequences induced by these absorbed radiological doses remain understudied and the long-term biological impacts largely unknown. We assessed the biological effects of chronic exposure to ionizing radiation (IR) on embryonic development by exposing zebrafish embryo from fertilization and up to 120 hours post-fertilization (hpf) at dose rates of 0.5 mGy/h, 5 mGy/h and 50 mGy/h, thereby encompassing the field of low dose rates defined at 6 mGy/h. Chronic exposure to IR altered larval behaviour in a light-dark locomotor test and affected cardiac activity at a dose rate as low as 0.5 mGy/h. The multi-omics analysis of transcriptome, proteome and transcription factor binding sites in the promoters of the deregulated genes, collectively points towards perturbations of neurogenesis, muscle development, and retinoic acid (RA) signaling after chronic exposure to iR. Whole-mount RnA in situ hybridization confirmed the impaired expression of the transcription factors her4.4 in the central nervous system and myogenin in the developing muscles of exposed embryos. At the organ level, the assessment of muscle histology by transmission electron microscopy (TEM) demonstrated myofibers disruption and altered neuromuscular junctions in exposed larvae at 5 mGy/h and 50 mGy/h. The integration of these multi-level data demonstrates that chronic exposure to low dose rates of iR has an impact on neuronal and muscle progenitor cells, that could lead to motility defects in free swimming larvae at 120 hpf. The mechanistic understanding of these effects allows us to propose a model where deregulation of RA signaling by chronic exposure to IR has pleiotropic effects on neurogenesis and muscle development.

Published
2019

44. Adverse effects induced by chronic gamma irradiation in progeny of adult fish not affecting parental reproductive performance

Author

Guirandy, Noémie, primary, Gagnaire, Béatrice, additional, Frelon, Sandrine, additional, Munch, Thomas, additional, Dubourg, Nicolas, additional, Camilleri, Virginie, additional, Cavalié, Isabelle, additional, Floriani, Magali, additional, Arcanjo, Caroline, additional, Murat El Houdigui, Sophia, additional, Armant, Olivier, additional, Adam‐Guillermin, Christelle, additional, Gonzalez, Patrice, additional, and Simon, Olivier, additional

Published
2019
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45. Effect of chronic low doses of ionizing radiations on central nervous system development of zebrafish

Author

Loro, Giovana, Murat El Houdigui, Sophia, DUBOURG, Nicolas, DELLA-VEDOVA, CLAIRE, BENADJAOUD, Mohamedamine, Adam-Guillermin, Christelle, ARMANT, Olivier, PSE-ENV/SRTE/LECO, Institut de Radioprotection et de Sûreté Nucléaire (IRSN), PSE-ENV/SRTE/LRTA, and PSE-SANTE/SERAMED

Subjects
[SDV]Life Sciences [q-bio]
Abstract

International audience; After the nuclear accidents at Chernobyl and Fukushima and due to a growing use of radionuclides, radiation protection of the environment is a major concern. Studies show an increased sensitivity to ionizing radiation (IR) during development. However, there are few data on the molecular mechanisms leading to the effects of IR on embryogenesis and moreover for chronic exposures. In this context, the objective of this thesis is to better understand the effects of exposure to IR on the development of zebrafish (Danio rerio), a model organism in ecotoxicology and in biomedicine. Fertilized eggs were exposed to gamma rays emitted by a 137Cs source at low to moderate dose rates (from 0.005 mGy/h to 50 mGy/h), then analysed from the gastrula stage (6 hours) to the larval stage (5 days) by an integrative approach from molecular effects to behavioural effects. Part of this work has focused on studying the effects of IR at an early stage of zebrafish development after exposure to IR. For this, a multi-omics approach with the study of the transcriptome and the methylome has been implemented. A transcriptomic study at the shield stage with dose rates ranging from 0.005 mGy/h to 50 mGy/h was carried out and demonstrated a moderate but significant effect on the regulation of oxidative stress and mitochondrial activity. At 5 and 50 mGy/h, the genes involved in the development of the central nervous system (CNS) and muscles are affected. The methylome study has revealed hypomethylation of the promoter sequences of genes involved in the development of the CNS and muscles, associated with a modification of gene expression. These results on early embryonic stages, highlight potential effects on the development of the CNS and muscles. The other part of this work focused on assessing the effects of IR exposure at later developmental stages using a system biology approach. For this, analyses were carried out from the molecular scale to the phenotypic scale. At the molecular level, a multi-omics analysis of the transcriptome and the proteome has highlighted the modulation of genes involved in the retinoic acid pathway, the development of the CNS and muscles in embryos and larvae exposed to 0.5; 5 and 50 mGy/h. Labelling by in-situ hybridization confirmed the misregulation of the transcription factors her4.4 in the CNS and myog in the muscles of embryos exposed to IR. At the tissue level, disruption of muscle myofibrils and alteration of neuromuscular junctions are detected in embryos exposed to 5 and 50 mGy/h. In order to assess an individual effect at phenotypic scale, the locomotor behaviour of the larvae was assessed under stress conditions. A significant decrease in larval motility was detected between 0.5 mGy/h and 50 mGy/h. This work has shown effects of IR on the development of the CNS and muscles from early development at the molecular level. These effects are confirmed at later stages of development. This study suggests that the molecular disturbances observed during early development are predictive of the effects observed at later developmental stages. In addition, this thesis work allows us to propose a model of "Adverse Outcome Pathway" where the deregulation of the retinoic acid pathway by exposure to IR will lead to effects on the development of the CNS and muscles.

Published
2019

46. Epigenetic modifications as a molecular mechanism for transgenerational effects in Daphnia exposed to ionising radiation

Author

TRIJAU, Marie, ASSELMAN, Jana, ARMANT, Olivier, Adam-Guillermin, Christelle, De Schamphelaere, Karel, ALONZO, Frederic, Ibacon GmbH, Ghent University, PSE-ENV/SRTE/LECO, and Institut de Radioprotection et de Sûreté Nucléaire (IRSN)

Subjects
[SDE]Environmental Sciences
Abstract

International audience; In order to predict long term consequences of pollution on wildlife, toxic effects have to be assessed on a multigenerational scale. DEBtox models were recently developped to analyze effects of alpha and gamma radiation over several generations of Daphnia magna. A transgenerational damage compartement which level is transmitted from parent to offspring, was used to account for changes in effect severity observed among generations. However, the nature of molecular mechanisms involved in the transmission of radio-induced damage accross generations are poorly understood. In this context, the role of epigenetic processes was recently investigated in D. magna, as part of the transgenerational response to external Cs-137 gamma irradiation (at dose rates of 6.5 µGy/h and 41.3 mGy/h). In this aim, we studied DNA methylation changes after a 25-day chronic exposure of a parental generation (F0) and their potential inheritance by subsequent recovering generations, including F2 (exposed as germ cells in F1 embryos) and F3 (the first truly unexposed generation). Effects on survival, growth and reproduction were examined in all generations and DNA was extracted for whole genome bisulfite sequencing. Results showed that effects on reproduction were significant in generation F0 at the high dose rate and absent in subsequent generations (F1, F2 and F3). In contrast, we detected significant DNA methylation changes in every generation independent of dose rate. Some of these changes were shared between dose rates and among generations. Involved genes included gene families and gene functions which were previously shown to play roles during exposure to ionising radiation. Common DNA methylation changes detected between generations F2 and F3 clearly showed that epigenetic modifications were transmitted to unexposed generations, most likely through the germline.

Published
2019

47. Loss of ASAP1 in mice impairs adipogenic and osteogenic differentiation of mesenchymal progenitor cells through dysregulation of FAK/Src and AKT signaling

Author

Schreiber, Caroline, primary, Saraswati, Supriya, additional, Harkins, Shannon, additional, Gruber, Annette, additional, Cremers, Natascha, additional, Thiele, Wilko, additional, Rothley, Melanie, additional, Plaumann, Diana, additional, Korn, Claudia, additional, Armant, Olivier, additional, Augustin, Hellmut G., additional, and Sleeman, Jonathan P., additional

Published
2019
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48. Characterization of the proneural gene regulatory network during mouse telencephalon development

Author

Parker Joel S, Nguyen Laurent, Castro Diogo S, Zimmer Celine, Smith Marjolein V, Parham Frederick M, Armant Olivier, Gohlke Julia M, Gradwohl Gerard, Portier Christopher J, and Guillemot François

Subjects
Biology (General), QH301-705.5
Abstract

Abstract Background The proneural proteins Mash1 and Ngn2 are key cell autonomous regulators of neurogenesis in the mammalian central nervous system, yet little is known about the molecular pathways regulated by these transcription factors. Results Here we identify the downstream effectors of proneural genes in the telencephalon using a genomic approach to analyze the transcriptome of mice that are either lacking or overexpressing proneural genes. Novel targets of Ngn2 and/or Mash1 were identified, such as members of the Notch and Wnt pathways, and proteins involved in adhesion and signal transduction. Next, we searched the non-coding sequence surrounding the predicted proneural downstream effector genes for evolutionarily conserved transcription factor binding sites associated with newly defined consensus binding sites for Ngn2 and Mash1. This allowed us to identify potential novel co-factors and co-regulators for proneural proteins, including Creb, Tcf/Lef, Pou-domain containing transcription factors, Sox9, and Mef2a. Finally, a gene regulatory network was delineated using a novel Bayesian-based algorithm that can incorporate information from diverse datasets. Conclusion Together, these data shed light on the molecular pathways regulated by proneural genes and demonstrate that the integration of experimentation with bioinformatics can guide both hypothesis testing and hypothesis generation.

Published
2008
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50. Suppression of dsRNA response genes and innate immunity following Oct4, Stella, and Nanos2 overexpression in mouse embryonic fibroblasts

Author

Farshchian, Moein, primary, Matin, Maryam M., additional, Armant, Olivier, additional, Geerts, Dirk, additional, Dastpak, Mahtab, additional, Nakhaei-Rad, Saeideh, additional, Tajeran, Massoumeh, additional, Jebelli, Amir, additional, Shahriyari, Mina, additional, Bahrami, Monireh, additional, Fallah, Ali, additional, Yaghoobi, Vesal, additional, Mirahmadi, Mahdi, additional, Abbaszadegan, Mohammad Reza, additional, and Bahrami, Ahmad Reza, additional

Published
2018
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