173 results on '"Armant, Olivier"'
Search Results
2. Editorial trend: adverse outcome pathway (AOP) and computational strategy — towards new perspectives in ecotoxicology
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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
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- 2023
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3. Population transcriptogenomics highlights impaired metabolism and small population sizes in tree frogs living in the Chernobyl Exclusion Zone
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Car, Clément, Gilles, André, Goujon, Elen, Muller, Marie-Laure Delignette, Camoin, Luc, Frelon, Sandrine, Burraco, Pablo, Granjeaud, Samuel, Baudelet, Emilie, Audebert, Stéphane, Orizaola, Germán, Armengaud, Jean, Tenenhaus, Arthur, Garali, Imène, Bonzom, Jean-Marc, and Armant, Olivier
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- 2023
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4. Tritiated thymidine induces developmental delay, oxidative stress and gene overexpression in developing zebrafish (Danio rerio)
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Schiano Di Lombo, Magali, Cavalié, Isabelle, Camilleri, Virginie, Armant, Olivier, Perrot, Yann, Cachot, Jérôme, and Gagnaire, Béatrice
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- 2023
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5. Systems toxicology of complex wood combustion aerosol reveals gaseous carbonyl compounds as critical constituents
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Dilger, Marco, Armant, Olivier, Ramme, Larissa, Mülhopt, Sonja, Sapcariu, Sean C., Schlager, Christoph, Dilger, Elena, Reda, Ahmed, Orasche, Jürgen, Schnelle-Kreis, Jürgen, Conlon, Thomas M., Yildirim, Ali Önder, Hartwig, Andrea, Zimmermann, Ralf, Hiller, Karsten, Diabaté, Silvia, Paur, Hanns-Rudolf, and Weiss, Carsten
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- 2023
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6. Altered ovarian transcriptome is linked to early mortality and abnormalities in zebrafish embryos after maternal exposure to gamma irradiation
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Guirandy, Noëmie, Armant, Olivier, Frelon, Sandrine, Pierron, Fabien, Geffroy, Benjamin, Daffe, Guillemine, Houdelet, Camille, Gonzalez, Patrice, and Simon, Olivier
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- 2023
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7. Insights into the modes of action of tritium on the early-life stages of zebrafish, Danio rerio, using transcriptomic and proteomic analyses
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Arcanjo, Caroline, Frelon, Sandrine, Armant, Olivier, Camoin, Luc, Audebert, Stéphane, Camilleri, Virginie, Cavalié, Isabelle, Adam-Guillermin, Christelle, and Gagnaire, Beatrice
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- 2023
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8. Ionizing radiation affects the demography and the evolution of Caenorhabditis elegans populations
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Quevarec, Loïc, Réale, Denis, Dufourcq-Sekatcheff, Elizabeth, Armant, Olivier, Adam-Guillermin, Christelle, and Bonzom, Jean-Marc
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- 2023
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9. Radiation Adverse Outcome pathways (AOPs): examining priority questions from an international horizon-style exercise.
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Chauhan, Vinita, Beaton, Danielle, Tollefsen, Knut Erik, Preston, Julian, Burtt, Julie J., Leblanc, Julie, Hamada, Nobuyuki, Azzam, Edouard I., Armant, Olivier, Bouffler, Simon, Azimzadeh, Omid, Moertl, Simone, Yamada, Yutaka, Tanaka III, Ignacia B., Kaiser, Jan Christian, Applegate, Kimberly, Laurier, Dominique, and Garnier-Laplace, Jacqueline
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NUCLEAR energy ,IONIZING radiation ,EXPOSURE dose ,RADIATION ,RESEARCH questions - Abstract
The Organisation for Economic Co-operation and Development (OECD) Adverse Outcome Pathway (AOP) Development Programme is being explored in the radiation field, as an overarching framework to identify and prioritize research needs that best support strengthening of radiation risk assessment and risk management strategies. To advance the use of AOPs, an international horizon-style exercise (HSE) was initiated through the Radiation/Chemical AOP Joint Topical Group (JTG) formed by the OECD Nuclear Energy Agency (NEA) High-Level Group on Low Dose Research (HLG-LDR) under the auspices of the Committee on Radiological Protection and Public Health (CRPPH). The intent of the HSE was to identify key research questions for consideration in AOP development that would help to reduce uncertainties in estimating the health risks following exposures to low dose and low dose-rate ionizing radiation. The HSE was conducted in several phases involving the solicitation of relevant questions, a collaborative review of open-ended candidate questions and an elimination exercise that led to the selection of 25 highest priority questions for the stated purpose. These questions were further ranked by over 100 respondents through an international survey. This final set of questions was judged to provide insights into how the OECD's AOP approach can be put into practice to meet the needs of hazard and risk assessors, regulators, and researchers. This paper examines the 25 priority questions in the context of hazard/risk assessment framework for ionizing radiation. By addressing the 25 priority questions, it is anticipated that constructed AOPs will have a high level of specificity, making them valuable tools for simplifying and prioritizing complex biological processes for use in developing revised radiation hazard and risk assessment strategies. [ABSTRACT FROM AUTHOR]
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- 2024
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10. Dose-dependent genomic DNA hypermethylation and mitochondrial DNA damage in Japanese tree frogs sampled in the Fukushima Daiichi area
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Gombeau, Kewin, Bonzom, Jean-Marc, Cavalié, Isabelle, Camilleri, Virginie, Orjollet, Daniel, Dubourg, Nicolas, Beaugelin-Seiller, Karine, Bourdineaud, Jean-Paul, Lengagne, Thierry, Armant, Olivier, Ravanat, Jean-Luc, and Adam-Guillermin, Christelle
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- 2020
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11. Citizen science in environmental health research: A comparison with conventional approaches and creation of a guidance tool issued from the LILAS initiative
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Laurent, Olivier, Gironza, Yara Carrejo, Ancelet, Sophie, Armant, Olivier, Bard, Denis, Baumgartner, Katia, Bortoli, Sylvie, Boudet, Céline, Chamaret, Philippe, Cormier, Stéphanie, David, Arthur, Desqueyroux, Hélène, Gerber, Mariette, Grimbuhler, Sonia, Mougin, Christian, Payrastre, Laurence, Schraub, Simon, Trousse, Brigitte, Reaud, Cynthia, and Charron, Sylvie
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- 2024
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12. Editorial trend: adverse outcome pathway (AOP) and computational strategy — towards new perspectives in ecotoxicology.
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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
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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]
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- 2024
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13. Characterization of Phormidium lacuna strains from the North Sea and the Mediterranean Sea for biotechnological applications
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Nies, Fabian, Wörner, Sybille, Wunsch, Nadja, Armant, Olivier, Sharma, Vikas, Hesselschwerdt, Anne, Falk, Fabian, Weber, Nora, Weiß, Julia, Trautmann, Andreas, Posten, Clemens, Prakash, Tulika, and Lamparter, Tilman
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- 2017
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14. Expression of a Barhl1a reporter in subsets of retinal ganglion cells and commissural neurons of the developing zebrafish brain
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Albadri, Shahad, Armant, Olivier, Aljand-Geschwill, Tairi, Del Bene, Filippo, Carl, Matthias, Strähle, Uwe, and Poggi, Lucia
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- 2020
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15. The in vitro PIG-A gene mutation assay: glycosylphosphatidylinositol (GPI)-related genotype-to-phenotype relationship in TK6 cells
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Krüger, Christopher T., Fischer, Bettina M., Armant, Olivier, Morath, Volker, Strähle, Uwe, and Hartwig, Andrea
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- 2016
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16. Two independent transcription initiation codes overlap on vertebrate core promoters
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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
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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 [...]
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- 2014
17. Radiation adverse outcome pathways (AOPs) are on the horizon: advancing radiation protection through an international Horizon-Style exercise.
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Burtt, Julie J., Leblanc, Julie, Randhawa, Kristi, Ivanova, Addie, Rudd, Murray A., Wilkins, Ruth, Azzam, Edouard I., Hecker, Markus, Horemans, Nele, Vandenhove, Hildegarde, Adam-Guillermin, Christelle, Armant, Olivier, Klokov, Dmitry, Audouze, Karine, Kaiser, Jan Christian, Moertl, Simone, Lumniczky, Katalin, Tanaka III, Ignacia B., Yamada, Yutaka, and Hamada, Nobuyuki
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RADIATION protection ,DOSE-response relationship (Radiation) ,NUCLEAR energy ,RADIATION ,ENERGY development - Abstract
The Adverse Outcome Pathway (AOP) framework, a systematic tool that can link available mechanistic data with phenotypic outcomes of relevance to regulatory decision-making, is being explored in areas related to radiation risk assessment. To examine the challenges including the use of AOPs to support the radiation protection community, an international horizon-style exercise was initiated through the Organisation for Economic Co-operation and Development Nuclear Energy Agency High-Level Group on Low Dose Research Radiation/Chemical AOP Joint Topical Group. The objective of the HSE was to facilitate the collection of ideas from a range of experts, to short-list a set of priority research questions that could, if answered, improve the description of the radiation dose-response relationship for low dose/dose-rate exposures, as well as reduce uncertainties in estimating the risk of developing adverse health outcomes following such exposures. The HSE was guided by an international steering committee of radiation risk experts. In the first phase, research questions were solicited on areas that can be supported by the AOP framework, or challenges on the use of AOPs in radiation risk assessment. In the second phase, questions received were refined and sorted by the SC using a best-worst scaling method. During a virtual 3-day workshop, the list of questions was further narrowed. In the third phase, an international survey of the broader radiation protection community led to an orderly ranking of the top questions. Of the 271 questions solicited, 254 were accepted and categorized into 9 themes. These were further refined to the top 25 prioritized questions. Among these, the higher ranked questions will be considered as 'important' to drive future initiatives in the low dose radiation protection community. These included questions on the ability of AOPs to delineate responses across different levels of biological organization, and how AOPs could be applied to address research questions on radiation quality, doses or dose-rates, exposure time patterns and deliveries, and uncertainties in low dose/dose-rate effects. A better understanding of these concepts is required to support the use of the AOP framework in radiation risk assessment. Through dissemination of these results and considerations on next steps, the JTG will address select priority questions to advance the development and use of AOPs in the radiation protection community. The major themes observed will be discussed in the context of their relevance to areas of research that support the system of radiation protection. [ABSTRACT FROM AUTHOR]
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- 2022
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18. Development of an adverse outcome pathway for radiation-induced microcephaly via expert consultation and machine learning.
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Jaylet, Thomas, Quintens, Roel, Benotmane, Mohamed Abderrafi, Luukkonen, Jukka, Tanaka III, Ignacia Braga, Ibanez, Chrystelle, Durand, Christelle, Sachana, Magdalini, Azimzadeh, Omid, Adam-Guillermin, Christelle, Tollefsen, Knut Erik, Laurent, Olivier, Audouze, Karine, and Armant, Olivier
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MACHINE learning ,MICROCEPHALY ,SCIENTIFIC knowledge ,IONIZING radiation ,SIZE of brain ,TOXICOLOGICAL interactions - Abstract
Brain development during embryogenesis and in early postnatal life is particularly complex and involves the interplay of many cellular processes and molecular mechanisms, making it extremely vulnerable to exogenous insults, including ionizing radiation (IR). Microcephaly is one of the most frequent neurodevelopmental abnormalities that is characterized by small brain size, and is often associated with intellectual deficiency. Decades of research span from epidemiological data on in utero exposure of the A-bomb survivors, to studies on animal and cellular models that allowed deciphering the most prominent molecular mechanisms leading to microcephaly. The Adverse Outcome Pathway (AOP) framework is used to organize, evaluate and portray the scientific knowledge of toxicological effects spanning different biological levels of organizations, from the initial interaction with molecular targets to the occurrence of a disease or adversity. In the present study, the framework was used in an attempt to organize the current scientific knowledge on microcephaly progression in the context of ionizing radiation (IR) exposure. This work was performed by a group of experts formed during a recent workshop organized jointly by the Multidisciplinary European Low Dose Initiative (MELODI) and the European Radioecology Alliance (ALLIANCE) associations to present the AOP approach and tools. Here we report on the development of a putative AOP for congenital microcephaly resulting from IR exposure based on discussions of the working group and we emphasize the use of a novel machine-learning approach to assist in the screening of the available literature to develop AOPs. The expert consultation led to the identification of crucial biological events for the progression of microcephaly upon exposure to IR, and highlighted current knowledge gaps. The machine learning approach was successfully used to screen the existing knowledge and helped to rapidly screen the body of evidence and in particular the epidemiological data. This systematic review approach also ensured that the analysis was sufficiently comprehensive to identify the most relevant data and facilitate rapid and consistent AOP development. We anticipate that as machine learning approaches become more user-friendly through easy-to-use web interface, this would allow AOP development to become more efficient and less time consuming. [ABSTRACT FROM AUTHOR]
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- 2022
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19. Comprehensive expression map of transcription regulators in the adult zebrafish telencephalon reveals distinct neurogenic niches
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Diotel, Nicolas, Viales, Rebecca Rodriguez, Armant, Olivier, März, Martin, Ferg, Marco, Rastegar, Sepand, and Strähle, Uwe
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- 2015
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20. Male frequency in Caenorhabditis elegans increases in response to chronic irradiation.
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Quevarec, Loïc, Réale, Denis, Dufourcq‐Sekatcheff, Elizabeth, Car, Clément, Armant, Olivier, Dubourg, Nicolas, Adam‐Guillermin, Christelle, and Bonzom, Jean‐Marc
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CAENORHABDITIS elegans ,CAENORHABDITIS ,RADIOACTIVE pollution ,IONIZING radiation ,SEX ratio ,MALES - Abstract
Outcrossing can be advantageous in a changing environment because it promotes the purge of deleterious mutations and increases the genetic diversity within a population, which may improve population persistence and evolutionary potential. Some species may, therefore, switch their reproductive mode from inbreeding to outcrossing when under environmental stress. This switch may have consequences on the demographic dynamics and evolutionary trajectory of populations. For example, it may directly influence the sex ratio of a population. However, much remains to be discovered about the mechanisms and evolutionary implications of sex ratio changes in a population in response to environmental stress. Populations of the androdioecious nematode Caenorhabditis elegans, are composed of selfing hermaphrodites and rare males. Here, we investigate the changes in the sex ratio of C. elegans populations exposed to radioactive pollution for 60 days or around 20 generations. We experimentally exposed populations to three levels of ionizing radiation (i.e., 0, 1.4, and 50 mGy.h−1). We then performed reciprocal transplant experiments to evaluate genetic divergence between populations submitted to different treatments. Finally, we used a mathematical model to examine the evolutionary mechanisms that could be responsible for the change in sex ratio. Our results showed an increase in male frequency in irradiated populations, and this effect increased with the dose rate. The model showed that an increase in male fertilization success or a decrease in hermaphrodite self‐fertilization could explain this increase in the frequency of males. Moreover, males persisted in populations after transplant back into the control conditions. These results suggested selection favoring outcrossing under irradiation conditions. This study shows that ionizing radiation can sustainably alter the reproductive strategy of a population, likely impacting its long‐term evolutionary history. This study highlights the need to evaluate the impact of pollutants on the reproductive strategies of populations when assessing the ecological risks. [ABSTRACT FROM AUTHOR]
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- 2022
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21. Proteome dynamics in neutrophils of adult zebrafish upon chemically-induced inflammation
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Singh, Sachin Kumar, Aravamudhan, Sriram, Armant, Olivier, Krüger, Marcus, and Grabher, Clemens
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- 2014
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22. Gene transcription in the zebrafish embryo: regulators and networks
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Ferg, Marco, Armant, Olivier, Yang, Lixin, Dickmeis, Thomas, Rastegar, Sepand, and Strähle, Uwe
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- 2014
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23. Neurogenin 2 controls cortical neuron migration through regulation of Rnd2
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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
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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 [...]
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- 2008
24. Fishing for melanoma markers through comparative transcriptome analysis
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Mione, Marina and Armant, Olivier
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- 2012
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25. Le projet LILAS : analyse de l'application des approches participatives sur les multi-expositions environnementales et les risques chroniques.
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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, Stéphane, Larqué, Lionel, Laurier, Dominique, and Mougin, Christian
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PARTICIPANT observation ,ENVIRONMENTAL health ,NONGOVERNMENTAL organizations ,ECOSYSTEM health ,PUBLIC health research ,ENVIRONMENTAL exposure ,ENVIRONMENTAL risk assessment - Abstract
Résumé: 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. 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. [ABSTRACT FROM AUTHOR]
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- 2022
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26. Unusual evolution of tree frog populations in the Chernobyl exclusion zone.
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Car, Clément, Gilles, André, Armant, Olivier, Burraco, Pablo, Beaugelin‐Seiller, Karine, Gashchak, Sergey, Camilleri, Virginie, Cavalié, Isabelle, Laloi, Patrick, Adam‐Guillermin, Christelle, Orizaola, Germán, and Bonzom, Jean‐Marc
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FROG populations ,HYLIDAE ,NUCLEAR power plant accidents ,IONIZING radiation ,HAPLOTYPES ,RADIOACTIVE contamination ,NUCLEAR power plants - Abstract
Despite the ubiquity of pollutants in the environment, their long‐term ecological consequences are not always clear and still poorly studied. This is the case concerning the radioactive contamination of the environment following the major nuclear accident at the Chernobyl nuclear power plant. Notwithstanding the implications of evolutionary processes on the population status, few studies concern the evolution of organisms chronically exposed to ionizing radiation in the Chernobyl exclusion zone. Here, we examined genetic markers for 19 populations of Eastern tree frog (Hyla orientalis) sampled in the Chernobyl region about thirty years after the nuclear power plant accident to investigate microevolutionary processes ongoing in local populations. Genetic diversity estimated from nuclear and mitochondrial markers showed an absence of genetic erosion and higher mitochondrial diversity in tree frogs from the Chernobyl exclusion zone compared to other European populations. Moreover, the study of haplotype network permitted us to decipher the presence of an independent recent evolutionary history of Chernobyl exclusion zone's Eastern tree frogs caused by an elevated mutation rate compared to other European populations. By fitting to our data a model of haplotype network evolution, we suspected that Eastern tree frog populations in the Chernobyl exclusion zone have a high mitochondrial mutation rate and small effective population sizes. These data suggest that Eastern tree frog populations might offset the impact of deleterious mutations because of their large clutch size, but also question the long‐term impact of ionizing radiation on the status of other species living in the Chernobyl exclusion zone. [ABSTRACT FROM AUTHOR]
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- 2022
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27. Multi-Dimensional Transcriptome Analysis Reveals Modulation of Cholesterol Metabolism as Highly Integrated Response to Brain Injury.
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Gourain, Victor, Armant, Olivier, Lübke, Luisa, Diotel, Nicolas, Rastegar, Sepand, and Strähle, Uwe
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CHOLESTEROL metabolism ,NERVOUS system regeneration ,BRAIN injuries ,LINCRNA ,GENETIC engineering ,HYDROXYCHOLESTEROLS ,INTRONS - Abstract
Zebrafish is an attractive model to investigate regeneration of the nervous system. Despite major progress in our understanding of the underlying processes, the transcriptomic changes are largely unknown. We carried out a computational analysis of the transcriptome of the regenerating telencephalon integrating changes in the expression of mRNAs, their splice variants and investigated the putative role of regulatory RNAs in the modulation of these transcriptional changes. Profound changes in the expression of genes and their splice variants engaged in many distinct processes were observed. Differential transcription and splicing are important processes in response to injury of the telencephalon. As exemplified by the coordinated regulation of the cholesterol synthesizing enzymes and transporters, the genome responded to injury of the telencephalon in a multi-tiered manner with distinct and interwoven changes in expression of enzymes, transporters and their regulatory molecules. This coordinated genomic response involved a decrease of the mRNA of the key transcription factor SREBF2, induction of microRNAs (miR-182 , miR-155 , miR-146 , miR-31) targeting cholesterol genes, shifts in abundance of splice variants as well as regulation of long non-coding RNAs. Cholesterol metabolism appears to be switched from synthesis to relocation of cholesterol. Based on our in silico analyses, this switch involves complementary and synergistic inputs by different regulatory principles. Our studies suggest that adaptation of cholesterol metabolism is a key process involved in regeneration of the injured zebrafish brain. [ABSTRACT FROM AUTHOR]
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- 2021
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28. Characterization of the proneural gene regulatory network during mouse telencephalon development
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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
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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.
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- 2008
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29. A systems biology approach reveals neuronal and muscle developmental defects after chronic exposure to ionising radiation in zebrafish.
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Murat El Houdigui, Sophia, Adam-Guillermin, Christelle, Loro, Giovanna, Arcanjo, Caroline, Frelon, Sandrine, Floriani, Magali, Dubourg, Nicolas, Baudelet, Emilie, Audebert, Stéphane, Camoin, Luc, and Armant, Olivier
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SYSTEMS biology ,MUSCLE growth ,CHRONIC diseases ,RADIOACTIVE substances ,TRANSCRIPTOMES - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2019
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30. Adverse effects induced by chronic gamma irradiation in progeny of adult fish not affecting parental reproductive performance.
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Guirandy, Noémie, Gagnaire, Béatrice, Frelon, Sandrine, Munch, Thomas, Dubourg, Nicolas, Camilleri, Virginie, Cavalié, Isabelle, Floriani, Magali, Arcanjo, Caroline, Murat El Houdigui, Sophia, Armant, Olivier, Adam‐Guillermin, Christelle, Gonzalez, Patrice, and Simon, Olivier
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ECOLOGICAL risk assessment ,MATERNAL exposure ,IRRADIATION ,EXPOSURE dose ,FISH reproduction - Abstract
Multigenerational studies have become of great interest in ecotoxicology since the consequence of parental exposure to contaminants on offspring generations was established in situ or in laboratory conditions. The present study mainly examined the chronic effects of external Cs‐137 gamma irradiation exposure at 4 dose rates (control, 0.5, 5, and 50 mGy h–1) on adult zebrafish (F0) exposed for 10 d and their progeny (F1) exposed or unexposed for 4 to 5 d. The main endpoints investigated included parental reproductive performance, embryo‐larval survival, DNA alterations, and reactive oxygen species (ROS) production in F0 and F1. No effects on reproductive success, fecundity, or egg fertilization rate were observed. However, drastic effects were observed on F1 exposed to 50 mGy h–1, resulting in a mortality rate of 100%. The drastic effects were also observed when the progeny was not irradiated. It was demonstrated that the sensitivity of the embryos was mainly attributable to parental irradiation. Moreover, these drastic effects induced by adult irradiation disappeared over time when 10 d–irradiated adults were placed in a nonirradiated condition. Alterations in larval DNA were observed for the 3 dose rates, and an increase of ROS production was also shown for the 2 lowest dose rates. The present study improves our understanding of the consequences of parental exposure conditions to the progeny. Furthermore, it provides an incentive to take transmitted generational effects into account in ecological risk assessments. Environ Toxicol Chem 2019;38:2556–2567. © 2019 SETAC [ABSTRACT FROM AUTHOR]
- Published
- 2019
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31. Loss of ASAP1 in mice impairs adipogenic and osteogenic differentiation of mesenchymal progenitor cells through dysregulation of FAK/Src and AKT signaling.
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Schreiber, Caroline, Saraswati, Supriya, Harkins, Shannon, Gruber, Annette, Cremers, Natascha, Thiele, Wilko, Rothley, Melanie, Plaumann, Diana, Korn, Claudia, Armant, Olivier, Augustin, Hellmut G., and Sleeman, Jonathan P.
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PROGENITOR cells ,CELL migration ,CONNECTIVE tissue cells ,DEVELOPMENTAL biology ,ADAPTOR proteins ,ADIPOGENESIS - Abstract
ASAP1 is a multi-domain adaptor protein that regulates cytoskeletal dynamics, receptor recycling and intracellular vesicle trafficking. Its expression is associated with poor prognosis for a variety of cancers, and promotes cell migration, invasion and metastasis. Little is known about its physiological role. In this study, we used mice with a gene-trap inactivated ASAP1 locus to study the functional role of ASAP1 in vivo, and found defects in tissues derived from mesenchymal progenitor cells. Loss of ASAP1 led to growth retardation and delayed ossification typified by enlarged hypertrophic zones in growth plates and disorganized chondro-osseous junctions. Furthermore, loss of ASAP1 led to delayed adipocyte development and reduced fat depot formation. Consistently, deletion of ASAP1 resulted in accelerated chondrogenic differentiation of mesenchymal cells in vitro, but suppressed osteo- and adipogenic differentiation. Mechanistically, we found that FAK/Src and PI3K/AKT signaling is compromised in Asap1
GT /GT MEFs, leading to impaired adipogenic differentiation. Dysregulated FAK/Src and PI3K/AKT signaling is also associated with attenuated osteogenic differentiation. Together these observations suggest that ASAP1 plays a decisive role during the differentiation of mesenchymal progenitor cells. [ABSTRACT FROM AUTHOR]- Published
- 2019
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32. Tritiated water exposure disrupts myofibril structure and induces mis-regulation of eye opacity and DNA repair genes in zebrafish early life stages.
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Arcanjo, Caroline, Armant, Olivier, Floriani, Magali, Cavalie, Isabelle, Camilleri, Virginie, Simon, Olivier, Orjollet, Daniel, Adam-Guillermin, Christelle, and Gagnaire, Béatrice
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DEVELOPMENTAL toxicology , *ZEBRA danio , *RADIOISOTOPES & the environment , *MYOFIBRILS , *DNA repair , *OPACITY (Optics) , *TOXICOLOGY of water pollution , *PHYSIOLOGY - Abstract
Tritium ( 3 H) is a radioactive isotope of hydrogen. In the environment, the most common form of tritium is tritiated water (HTO). The present study aimed to identify early biomarkers of HTO contamination through the use of an aquatic model, the zebrafish ( Danio rerio ). We used the zebrafish embryo-larvae model to investigate the modes of action of HTO exposure at dose rates of 0.4 and 4 mGy/h, dose rates expected to induce deleterious effects on fish. Zebrafish were exposed to HTO from 3 hpf (hours post fertilization) to 96 hpf. The transcriptomic effects were investigated 24 h and 96 h after the beginning of the contamination, using mRNAseq. Results suggested an impact of HTO contamination, regardless of the dose rate, on genes involved in muscle contraction ( tnnt2d , tnni2a.4, slc6a1a or atp2a1l ) and eye opacity ( crygm2d9 , crygmxl1 , mipb or lim2.3 ) after 24 h of contamination. Interestingly, an opposite differential expression was highlighted in genes playing a role in muscle contraction and eye opacity in 24 hpf embryos when comparing dose rates, suggesting an onset of DNA protective mechanisms. The expression of h2afx and ddb2 involved in DNA repair was enhanced in response to HTO exposure. The entrainment of circadian clock and the response to H 2 O 2 signalling pathways were enriched at 96 hpf at 0.4 mGy/h and in both stages after 4 mGy/h. Genes involved in ROS scavenging were differentially expressed only after 24 h of exposure for the lowest dose rate, suggesting the onset of early protective mechanisms against oxidative stress. Effects highlighted on muscle at the molecular scale were confirmed at a higher biological scale, as electron microscopy observations revealed sarcomere impairments in 96 hpf larvae for both dose rates. Together with other studies, the present work provides useful data to better understand modes of action of tritium on zebrafish embryos-larvae. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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33. zHSF1 modulates zper2 expression in zebrafish embryos.
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Mennetrier, Lucas, Lopez, Tatiana, Pruvot, Benoist, Yousfi, Nadhir, Armant, Olivier, Hazhaz, Hanae, Lhuissiez, Vincent, Garrido, Carmen, and Chluba, Johanna
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CIRCADIAN rhythms ,EMBRYOS ,ZEBRA danio ,TRANSCRIPTION factors ,PROTEIN genetics - Abstract
HSF1 is a transcription factor that plays a key role in circadian resetting by temperature. We have used zebrafish embryos to decipher the roles of zHsf1, heat and light on zper2 transcription in vivo. Our results show that heat shock (HS) stimulated zper2 expression in the dark but has no cumulative effect combined with light. After light exposition, zper2 expression was 2.7 fold increased threefold in the hsf1-morphants in comparison to control embryos. Our results show that zHsf1 plays a positive role in HS-driven expression of zper2 in the dark but seems to act as an attenuator in the presence light. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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34. Transgenerational DNA Methylation Changes in Daphnia magna Exposed to Chronic γ Irradiation.
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Trijau, Marie, Asselman, Jana, Armant, Olivier, Adam-Guillermin, Christelle, De Schamphelaere, Karel A. C., and Alonzo, Frédéric
- Published
- 2018
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35. Development of Bag-1L as a therapeutic target in androgen receptor-dependent prostate cancer.
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Cato, Laura, Neeb, Antje, Sharp, Adam, Buzón, Victor, Ficarro, Scott B., Linxiao Yang, Muhle-Goll, Claudia, Kuznik, Nane C., Riisnaes, Ruth, Rodrigues, Daniel Nava, Armant, Olivier, Gourain, Victor, Adelmant, Guillaume, Ntim, Emmanuel A., Westerling, Thomas, Dolling, David, Rescigno, Pasquale, Figueiredo, Ines, Fauser, Friedrich, and Wu, Jennifer
- Published
- 2017
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36. Zebrafish exposure to environmentally relevant concentration of depleted uranium impairs progeny development at the molecular and histological levels.
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Armant, Olivier, Gombeau, Kewin, Murat El Houdigui, Sophia, Floriani, Magali, Camilleri, Virginie, Cavalie, Isabelle, and Adam-Guillermin, Christelle
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ZEBRA danio , *ENVIRONMENTAL exposure , *DEPLETED uranium , *HISTOLOGY , *ANTHROPOGENIC effects on nature - Abstract
Uranium is an actinide naturally found in the environment. Anthropogenic activities lead to the release of increasing amounts of uranium and depleted uranium (DU) in the environment, posing potential risks to aquatic organisms due to radiological and chemical toxicity of this radionucleide. Although environmental contaminations with high levels of uranium have already been observed, chronic exposures of non-human species to levels close to the environmental quality standards remain scarcely characterized. The present study focused on the identification of the molecular pathways impacted by a chronic exposure of zebrafish to 20 μg/L of DU during 10 days. The transcriptomic effects were evaluated by the use of the mRNAseq analysis in three organs of adult zebrafish, the brain the testis and the ovaries, and two developmental stages of the adult fish progeny, two-cells embryo and four-days larvae. The results highlight generic effects on the cell adhesion process, but also specific transcriptomic responses depending on the organ or the developmental stage investigated. The analysis of the transgenerational effects of DU-exposure on the four-day zebrafish larvae demonstrate an induction of genes involved in oxidative response (cat, mpx, sod1 and sod2), a decrease of expression of the two hatching enzymes (he1a and he1b), the deregulation of the expression of gene coding for the ATPase complex and the induction of cellular stress. Electron microscopy analysis of skeletal muscles on the four-days larvae highlights significant histological impacts on the ultrastructure of both the mitochondria and the myofibres. In addition, the comparison with the transcriptomic data obtained for the acetylcholine esterase mutant reveals the induction of protein-chaperons in the skeletal muscles of the progeny of fish chronically exposed to DU, pointing towards long lasting effects of this chemical in the muscles. The results presented in this study support the hypothesis that a chronic parental exposure to an environmentally relevant concentration of DU could impair the progeny development with significant effects observed both at the molecular level and on the histological ultrastructure of organs. This study provides a comprehensive transcriptomic dataset useful for ecotoxicological studies on other fish species at the molecular level. It also provides a key DU responsive gene, egr1, which may be a candidate biomarker for monitoring aquatic pollution by heavy metals. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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37. Lmx1b is required for the glutamatergic fates of a subset of spinal cord neurons.
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Hilinski, William C., Bostrom, Jonathan R., England, Samantha J., Juárez-Morales, José L., de Jager, Sarah, Armant, Olivier, Legradi, Jessica, Strähle, Uwe, Link, Brian A., and Lewis, Katharine E.
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TRANSCRIPTION factors ,SPINAL cord ,INTERNEURONS ,EXCITATORY amino acid agents ,NEUROTRANSMITTERS - Abstract
Background: Alterations in neurotransmitter phenotypes of specific neurons can cause imbalances in excitation and inhibition in the central nervous system (CNS), leading to diseases. Therefore, the correct specification and maintenance of neurotransmitter phenotypes is vital. As with other neuronal properties, neurotransmitter phenotypes are often specified and maintained by particular transcription factors. However, the specific molecular mechanisms and transcription factors that regulate neurotransmitter phenotypes remain largely unknown. Methods: In this paper we use single mutant, double mutant and transgenic zebrafish embryos to elucidate the functions of Lmx1ba and Lmx1bb in the regulation of spinal cord interneuron neurotransmitter phenotypes. Results: We demonstrate that lmx1ba and lmx1bb are both expressed in zebrafish spinal cord and that lmx1bb is expressed by both V0v cells and dI5 cells. Our functional analyses demonstrate that these transcription factors are not required for neurotransmitter fate specification at early stages of development, but that in embryos with at least two lmx1ba and/or lmx1bb mutant alleles there is a reduced number of excitatory (glutamatergic) spinal interneurons at later stages of development. In contrast, there is no change in the numbers of V0v or dI5 cells. These data suggest that lmx1b-expressing spinal neurons still form normally, but at least a subset of them lose, or do not form, their normal excitatory fates. As the reduction in glutamatergic cells is only seen at later stages of development, Lmx1b is probably required either for the maintenance of glutamatergic fates or to specify glutamatergic phenotypes of a subset of later forming neurons. Using double labeling experiments, we also show that at least some of the cells that lose their normal glutamatergic phenotype are V0v cells. Finally, we also establish that Evx1 and Evx2, two transcription factors that are required for V0v cells to acquire their excitatory neurotransmitter phenotype, are also required for lmx1ba and lmx1bb expression in these cells, suggesting that Lmx1ba and Lmx1bb act downstream of Evx1 and Evx2 in V0v cells. Conclusions: Lmx1ba and Lmx1bb function at least partially redundantly in the spinal cord and three functional lmx1b alleles are required in zebrafish for correct numbers of excitatory spinal interneurons at later developmental stages. Taken together, our data significantly enhance our understanding of how spinal cord neurotransmitter fates are regulated. [ABSTRACT FROM AUTHOR]
- Published
- 2016
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38. Loss of function of myosin chaperones triggers Hsf1-mediated transcriptional response in skeletal muscle cells.
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Etard, Christelle, Armant, Olivier, Roostalu, Urmas, Gourain, Victor, Ferg, Marco, and Strähle, Uwe
- Published
- 2015
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39. The Helix-Loop-Helix Protein Id1 Controls Stem Cell Proliferation During Regenerative Neurogenesis in the Adult Zebrafish Telencephalon.
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Viales, Rebecca Rodriguez, Diotel, Nicolas, Ferg, Marco, Armant, Olivier, Eich, Julia, März, Martin, Rastegar, Sepand, Strähle, Uwe, Alunni, Alessandro, and Bally-Cuif, Laure
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HELIX-loop-helix motifs ,STEM cells ,GENETIC transcription ,DEVELOPMENTAL neurobiology ,TELENCEPHALON - Abstract
The teleost brain has the remarkable ability to generate new neurons and to repair injuries during adult life stages. Maintaining life-long neurogenesis requires careful management of neural stem cell pools. In a genome-wide expression screen for transcription regulators, the id1 gene, encoding a negative regulator of E-proteins, was found to be upregulated in response to injury. id1 expression was mapped to quiescent type I neural stem cells in the adult telencephalic stem cell niche. Gain and loss of id1 function in vivo demonstrated that Id1 promotes stem cell quiescence. The increased id1 expression observed in neural stem cells in response to injury appeared independent of inflammatory signals, suggesting multiple antagonistic pathways in the regulation of reactive neurogenesis. Together, we propose that Id1 acts to maintain the neural stem cell pool by counteracting neurogenesis-promoting signals. S tem C ells 2015;33:892-903 [ABSTRACT FROM AUTHOR]
- Published
- 2015
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40. Molecular Description of Eye Defects in the Zebrafish Pax6b Mutant, sunrise, Reveals a Pax6b-Dependent Genetic Network in the Developing Anterior Chamber.
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Takamiya, Masanari, Weger, Benjamin D., Schindler, Simone, Beil, Tanja, Yang, Lixin, Armant, Olivier, Ferg, Marco, Schlunck, Günther, Reinhard, Thomas, Dickmeis, Thomas, Rastegar, Sepand, and Strähle, Uwe
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EYE abnormalities ,ZEBRA danio ,FISH mutation ,FISH genetics ,GENE expression ,TUMOR classification - Abstract
The cornea is a central component of the camera eye of vertebrates and even slight corneal disturbances severely affect vision. The transcription factor PAX6 is required for normal eye development, namely the proper separation of the lens from the developing cornea and the formation of the iris and anterior chamber. Human PAX6 mutations are associated with severe ocular disorders such as aniridia, Peters anomaly and chronic limbal stem cell insufficiency. To develop the zebrafish as a model for corneal disease, we first performed transcriptome and in situ expression analysis to identify marker genes to characterise the cornea in normal and pathological conditions. We show that, at 7 days post fertilisation (dpf), the zebrafish cornea expresses the majority of marker genes (67/84 tested genes) found also expressed in the cornea of juvenile and adult stages. We also characterised homozygous pax6b mutants. Mutant embryos have a thick cornea, iris hypoplasia, a shallow anterior chamber and a small lens. Ultrastructure analysis revealed a disrupted corneal endothelium. pax6b mutants show loss of corneal epithelial gene expression including regulatory genes (sox3, tfap2a, foxc1a and pitx2). In contrast, several genes (pitx2, ctnnb2, dcn and fabp7a) were ectopically expressed in the malformed corneal endothelium. Lack of pax6b function leads to severe disturbance of the corneal gene regulatory programme. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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41. Whole genome and transcriptome analyses of environmental antibiotic sensitive and multi-resistant P seudomonas aeruginosa isolates exposed to waste water and tap water.
- Author
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Schwartz, Thomas, Kirchen, Silke, Dötsch, Andreas, Armant, Olivier, Bretschneider, Nancy, Hahn, Alexander, and Seifert, Martin
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PSEUDOMONAS aeruginosa ,SEWAGE microbiology ,DRINKING water analysis ,DRINKING water microbiology ,PHYSIOLOGICAL effects of antibiotics - Abstract
The fitness of sensitive and resistant P seudomonas aeruginosa in different aquatic environments depends on genetic capacities and transcriptional regulation. Therefore, an antibiotic-sensitive isolate PA30 and a multi-resistant isolate PA49 originating from waste waters were compared via whole genome and transcriptome Illumina sequencing after exposure to municipal waste water and tap water. A number of different genomic islands (e.g. PAGIs, PAPIs) were identified in the two environmental isolates beside the highly conserved core genome. Exposure to tap water and waste water exhibited similar transcriptional impacts on several gene clusters (antibiotic and metal resistance, genetic mobile elements, efflux pumps) in both environmental P . aeruginosa isolates. The MexCD- OprJ efflux pump was overexpressed in PA49 in response to waste water. The expression of resistance genes, genetic mobile elements in PA49 was independent from the water matrix. Consistently, the antibiotic sensitive strain PA30 did not show any difference in expression of the intrinsic resistance determinants and genetic mobile elements. Thus, the exposure of both isolates to polluted waste water and oligotrophic tap water resulted in similar expression profiles of mentioned genes. However, changes in environmental milieus resulted in rather unspecific transcriptional responses than selected and stimuli-specific gene regulation. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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42. Development of the prethalamus is crucial for thalamocortical projection formation and is regulated by Olig2.
- Author
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Katsuhiko Ono, Clavairoly, Adrien, Tadashi Nomura, Hitoshi Gotoh, Aoi Uno, Armant, Olivier, Hirohide Takebayashi, Qi Zhang, Kenji Shimamura, Shigeyoshi Itohara, Parras, Carlos M., and Kazuhiro Ikenaka
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NEURAL circuitry ,TRANSCRIPTION factors ,THALAMUS ,PROGENITOR cells ,NEURONS - Abstract
Thalamocortical axons (TCAs) pass through the prethalamus in the first step of their neural circuit formation. Although it has been supposed that the prethalamus is an intermediate target for thalamocortical projection formation, much less is known about the molecular mechanisms of this targeting. Here, we demonstrated the functional implications of the prethalamus in the formation of this neural circuit. We show that Olig2 transcription factor, which is expressed in the ventricular zone (VZ) of prosomere 3, regulates prethalamus formation, and loss of Olig2 results in reduced prethalamus size in early development, which is accompanied by expansion of the thalamic eminence (TE). Extension of TCAs is disorganized in the Olig2-KO dorsal thalamus, and initial elongation of TCAs is retarded in the Olig2- KO forebrain. Microarray analysis demonstrated upregulation of several axon guidancemolecules, including Epha3 and Epha5, in theOlig2-KO basal forebrain. In situ hybridization showed that the prethalamus in the wild type excluded the expression of Epha3 and Epha5, whereas loss of Olig2 resulted in reduction of this Ephas-negative area and the corresponding expansion of the Ephas-positive TE. Dissociated cultures of thalamic progenitor cells demonstrated that substrate-bound EphA3 suppresses neurite extension from dorsal thalamic neurons. These results indicate that Olig2 is involved in correct formation of the prethalamus, which leads to exclusion of the EphA3-expressing region and is crucial for proper TCA formation. Our observation is the first report showing the molecular mechanisms underlying how the prethalamus acts on initial thalamocortical projection formation. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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43. Genome-wide, whole mount in situ analysis of transcriptional regulators in zebrafish embryos.
- Author
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Armant, Olivier, März, Martin, Schmidt, Rebecca, Ferg, Marco, Diotel, Nicolas, Ertzer, Raymond, Bryne, Jan Christian, Yang, Lixin, Baader, Isabelle, Reischl, Markus, Legradi, Jessica, Mikut, Ralf, Stemple, Derek, IJcken, Wilfred van, van der Sloot, Antoine, Lenhard, Boris, Strähle, Uwe, and Rastegar, Sepand
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ZEBRA danio embryos , *GENETIC transcription regulation , *FISH genomes , *COMBINATORIAL chemistry , *HOMEOSTASIS , *VERTEBRATE development - Abstract
Abstract: Transcription is the primary step in the retrieval of genetic information. A substantial proportion of the protein repertoire of each organism consists of transcriptional regulators (TRs). It is believed that the differential expression and combinatorial action of these TRs is essential for vertebrate development and body homeostasis. We mined the zebrafish genome exhaustively for genes encoding TRs and determined their expression in the zebrafish embryo by sequencing to saturation and in situ hybridisation. At the evolutionary conserved phylotypic stage, 75% of the 3302 TR genes encoded in the genome are already expressed. The number of expressed TR genes increases only marginally in subsequent stages and is maintained during adulthood suggesting important roles of the TR genes in body homeostasis. Fewer than half of the TR genes (45%, n=1711 genes) are expressed in a tissue-restricted manner in the embryo. Transcripts of 207 genes were detected in a single tissue in the 24h embryo, potentially acting as regulators of specific processes. Other TR genes were expressed in multiple tissues. However, with the exception of certain territories in the nervous system, we did not find significant synexpression suggesting that most tissue-restricted TRs act in a freely combinatorial fashion. Our data indicate that elaboration of body pattern and function from the phylotypic stage onward relies mostly on redeployment of TRs and post-transcriptional processes. [Copyright &y& Elsevier]
- Published
- 2013
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44. Gene Responses in the Central Nervous System of Zebrafish Embryos Exposed to the Neurotoxicant Methyl Mercury.
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Nga Yu Ho, Lixin Yang, Legradi, Jessica, Armant, Olivier, Takamiya, Masanari, Rastegar, Sepand, and Strähle, Uwe
- Published
- 2013
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45. Expression at the Imprinted Dlk1-Gtl2 Locus Is Regulated by Proneural Genes in the Developing Telencephalon.
- Author
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Seibt, Julie, Armant, Olivier, Le Digarcher, Anne, Castro, Diogo, Ramesh, Vidya, Journot, Laurent, Guillemot, François, Vanderhaeghen, Pierre, and Bouschet, Tristan
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- *
ARABIDOPSIS , *TRANSCRIPTION factors , *GIBBERELLINS , *TRANSGENIC rice , *TRANSGENIC plants ,RICE genetics - Abstract
Imprinting is an epigenetic mechanism that restrains the expression of about 100 genes to one allele depending on its parental origin. Several imprinted genes are implicated in neurodevelopmental brain disorders, such as autism, Angelman, and Prader-Willi syndromes. However, how expression of these imprinted genes is regulated during neural development is poorly understood. Here, using single and double KO animals for the transcription factors Neurogenin2 (Ngn2) and Achaetescute homolog 1 (Ascl1), we found that the expression of a specific subset of imprinted genes is controlled by these proneural genes. Using in situ hybridization and quantitative PCR, we determined that five imprinted transcripts situated at the Dlk1-Gtl2 locus (Dlk1, Gtl2, Mirg, Rian, Rtl1) are upregulated in the dorsal telencephalon of Ngn2 KO mice. This suggests that Ngn2 influences the expression of the entire Dlk1-Gtl2 locus, independently of the parental origin of the transcripts. Interestingly 14 other imprinted genes situated at other imprinted loci were not affected by the loss of Ngn2. Finally, using Ngn2/Ascl1 double KO mice, we show that the upregulation of genes at the Dlk1-Gtl2 locus in Ngn2 KO animals requires a functional copy of Ascl1. Our data suggest a complex interplay between proneural genes in the developing forebrain that control the level of expression at the imprinted Dlk1-Gtl2 locus (but not of other imprinted genes). This raises the possibility that the transcripts of this selective locus participate in the biological effects of proneural genes in the developing telencephalon. [ABSTRACT FROM AUTHOR]
- Published
- 2012
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46. The Light Responsive Transcriptome of the Zebrafish: Function and Regulation.
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Weger, Benjamin D., Sahinbas, Meltem, Otto, Georg W., Mracek, Philipp, Armant, Olivier, Dolle, Dirk, Lahiri, Kajori, Vallone, Daniela, Ettwiller, Laurence, Geisler, Robert, Foulkes, Nicholas S., and Dickmeis, Thomas
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ZEBRA danio ,CELL lines ,CLUSTER analysis (Statistics) ,GENE expression ,DNA repair - Abstract
Most organisms possess circadian clocks that are able to anticipate the day/night cycle and are reset or ''entrained'' by the ambient light. In the zebrafish, many organs and even cultured cell lines are directly light responsive, allowing for direct entrainment of the clock by light. Here, we have characterized light induced gene transcription in the zebrafish at several organizational levels. Larvae, heart organ cultures and cell cultures were exposed to 1- or 3-hour light pulses, and changes in gene expression were compared with controls kept in the dark. We identified 117 light regulated genes, with the majority being induced and some repressed by light. Cluster analysis groups the genes into five major classes that show regulation at all levels of organization or in different subset combinations. The regulated genes cover a variety of functions, and the analysis of gene ontology categories reveals an enrichment of genes involved in circadian rhythms, stress response and DNA repair, consistent with the exposure to visible wavelengths of light priming cells for UV-induced damage repair. Promoter analysis of the induced genes shows an enrichment of various short sequence motifs, including E- and D-box enhancers that have previously been implicated in light regulation of the zebrafish period2 gene. Heterologous reporter constructs with sequences matching these motifs reveal light regulation of D-box elements in both cells and larvae. Morpholino-mediated knock-down studies of two homologues of the D-box binding factor Tef indicate that these are differentially involved in the cell autonomous light induction in a gene-specific manner. These findings suggest that the mechanisms involved in period2 regulation might represent a more general pathway leading to light induced gene expression. [ABSTRACT FROM AUTHOR]
- Published
- 2011
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47. A systems biology analysis of reproductive toxicity effects induced by multigenerational exposure to ionizing radiation in C. elegans.
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Guédon, Rémi, Maremonti, Erica, Armant, Olivier, Galas, Simon, Brede, Dag Anders, and Lecomte-Pradines, Catherine
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IONIZING radiation ,RADIATION exposure ,SYSTEMS biology ,GAMMA rays ,CAENORHABDITIS elegans ,LIPID metabolism ,GONADS - Abstract
Understanding the effects of chronic exposure to pollutants over generations is of primary importance for the protection of humans and the environment; however, to date, knowledge on the molecular mechanisms underlying multigenerational adverse effects is scarce. We employed a systems biology approach to analyze effects of chronic exposure to gamma radiation at molecular, tissue and individual levels in the nematode Caenorhabditis elegans. Our data show a decrease of 23% in the number of offspring on the first generation F0 and more than 40% in subsequent generations F1, F2 and F3. To unveil the impact on the germline, an in-depth analysis of reproductive processes involved in gametes formation was performed for all four generations. We measured a decrease in the number of mitotic germ cells accompanied by increased cell-cycle arrest in the distal part of the gonad. Further impact on the germline was manifested by decreased sperm quantity and quality. In order to obtain insight in the molecular mechanisms leading to decreased fecundity, gene expression was investigated via whole genome RNA sequencing. The transcriptomic analysis revealed modulation of transcription factors, as well as genes involved in stress response, unfolded protein response, lipid metabolism and reproduction. Furthermore, a drastic increase in the number of differentially expressed genes involved in defense response was measured in the last two generations, suggesting a cumulative stress effect of ionizing radiation exposure. Transcription factor binding site enrichment analysis and the use of transgenic strain identified daf-16/FOXO as a master regulator of genes differentially expressed in response to radiation. The presented data provide new knowledge with respect to the molecular mechanisms involved in reproductive toxic effects and accumulated stress resulting from multigenerational exposure to ionizing radiation. [Display omitted] • Multigenerational exposure to gamma radiation caused reproductive toxicity effects. • Radiation significantly reduced number of mitotic cells as well as quality of sperm. • A progressive transcriptomic stress response is induced by gamma radiation. • DAF-16/FOXO is a central regulator of the transcriptomic stress response. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
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48. Characterization of the proneural gene regulatory network during mouse telencephalon development.
- Author
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Gohlke, Julia M., Armant, Olivier, Parham, Frederick M., Smith, Marjolein V., Zimmer, Celine, Castro, Diogo S., Nguyen, Laurent, Parker, Joel S., Gradwohl, Gerard, Portier, Christopher J., and Guillemot, François
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GENES , *TELENCEPHALON , *PROTEINS , *DEVELOPMENTAL neurobiology , *TRANSCRIPTION factors , *NOTCH genes , *BIOINFORMATICS - 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. [ABSTRACT FROM AUTHOR]
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- 2008
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49. Sequential phases of cortical specification involve Neurogenin-dependent and -independent pathways.
- Author
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Schuurmans, Carol, Armant, Olivier, Nieto, Marta, Stenman, Jan M., Britz, Olivier, Klenin, Natalia, Brown, Craig, Langevin, Lisa-Marie, Seibt, Julie, Tang, Hua, Cunningham, James M., Dyck, Richard, Walsh, Christopher, Campbell, Kenny, Polleux, Franck, and Guillemot, François
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NEURONS , *CELL morphology , *MORPHOLOGY , *PHENOTYPES , *GENETICS , *MOLECULAR biology - Abstract
Neocortical projection neurons, which segregate into six cortical layers according to their birthdate, have diverse morphologies, axonal projections and molecular profiles, yet they share a common cortical regional identity and glutamatergic neurotransmission phenotype. Here we demonstrate that distinct genetic programs operate at different stages of corticogenesis to specify the properties shared by all neocortical neurons. Ngn1 and Ngn2 are required to specify the cortical (regional), glutamatergic (neurotransmitter) and laminar (temporal) characters of early-born (lower-layer) neurons, while simultaneously repressing an alternative subcortical, GABAergic neuronal phenotype. Subsequently, later-born (upper-layer) cortical neurons are specified in an Ngn-independent manner, requiring instead the synergistic activities of Pax6 and Tlx, which also control a binary choice between cortical/glutamatergic and subcortical/GABAergic fates. Our study thus reveals an unanticipated heterogeneity in the genetic mechanisms specifying the identity of neocortical projection neurons. [ABSTRACT FROM AUTHOR]
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- 2004
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50. Brain Damage and Repair: From Molecular Effects to Central Nervous System Disorders.
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Armant, Olivier and Adam-Guillermin, Christelle
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CENTRAL nervous system , *BRAIN damage , *SCIENTIFIC knowledge , *DEVELOPMENTAL neurobiology , *NEUROTROPHIC functions , *ISCHEMIC stroke - Abstract
In this special issue, three original research articles highlight how novel, state-of-the art irradiation tools can be employed as alternatives to bulk whole body exposure, in order to delineate the consequences of cell depletion, on organ function. 33291358 2 Suzuki M., Soh Z., Yamashita H., Tsuji T., Funayama T. Targeted Central Nervous System Irradiation of Caenorhabditis elegans Induces a Limited Effect on Motility. Chronical exposures to biological, chemical and physical stressors can be particularly detrimental during the early phase of embryonic development, increasing the risk of brain dysfunctions after birth. [Extracted from the article]
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- 2021
- Full Text
- View/download PDF
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