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International audience; Les systèmes d’eye-tracking permettent d’étudier les comportements visuels. Pour que les données de ces systèmes soient précises, la calibration est primordiale. Une bonne calibration se traduit par des valeurs de précision et de justesse faibles. Dans cette étude exploratoire, pour évaluer l’effet de la distance, de la luminosité et de l’angle de calibration sur la précision et la justesse de lunettes d’eye-tracking, des mesures ont été effectuées en champ visuel proche, intermédiaire et éloigné sur un écran de calibrage. Neuf combinaisons de calibration ont été testées selon un plan en carré latin. La distance, la luminosité et l’angle de calibration n’ont pas d’effet significatif sur la précision et la justesse des lunettes. A l’inverse, la précision et la justesse des lunettes sont meilleures en champ éloigné, qu’en champ proche et intermédiaire. Ces résultats montrent que les lunettes d’eye-tracking sont davantage adaptées à des études de terrain.

International audience; Recent studies have revealed a possible link between the activities of polymorphic arylamine N-acetyltransferases (NATs) and energy metabolism. We used a Nat1/Nat2 double knockout (KO) mouse model to demonstrate that ablation of the two Nat genes is associated with modest, intermittent alterations in respiratory exchange rate. Pyruvate tolerance tests show that double KO mice have attenuated hepatic gluconeogenesis when maintained on a high-fat/high-sucrose diet. Absence of the two Nat genes also leads to an increase in the hepatic concentration of coenzyme A in mice fed a high-fat/high-sucrose diet. Our results suggest a modest involvement of NAT in energy metabolism in mice, which is consistent with the absence of major phenotypic deregulation of energy metabolism in slow human acetylators.

Energy-dense food alters dopaminergic (DA) transmission in the mesocorticolimbic (MCL) system and can promote reward dysfunctions, compulsive feeding, and weight gain. Yet the mechanisms by which nutrients influence the MCL circuitry remain elusive. Here, we show that nutritional triglycerides (TGs), a conserved post-prandial metabolic signature among mammals, can be metabolized within the MCL system and modulate DA-associated behaviors by gating the activity of dopamine receptor subtype 2 (DRD2)-expressing neurons through a mechanism that involves the action of the lipoprotein lipase (LPL). Further, we show that in humans, post-prandial TG excursions modulate brain responses to food cues in individuals carrying a genetic risk for reduced DRD2 signaling. Collectively, these findings unveil a novel mechanism by which dietary TGs directly alter signaling in the reward circuit to regulate behavior, thereby providing a new mechanistic basis by which energy-rich diets may lead to (mal)adaptations in DA signaling that underlie reward deficit and compulsive behavior.

As service continuity is compelling for companies in order to satisfy their customers, maintenance quality and efficiency has become key points in the industry. To maintain their competitiveness, industrial companies strive to improve the efficiency and productivity of maintenance operations while keeping a very high level of safety. By equipping maintenance operators with a smartphone or tablet and smartglasses, the project aims at giving the right contextualized information. So that operators can better comprehend the context in which they work (e.g. for visualizing documents, notices or technical diagrams, interacting with a remote expert, connecting to an information system...) The prospective study presented is based on an ergonomic approach and user-centered approach (observations, interviews, cognitive-discursive analysis-CDA-and need characterization). It identifies a panel of new interaction technologies that best respond to operators' expectations and industrial requirements and still being able to adapt to complex and diverse environments., RESUME Dans un monde où la continuité de service est impérative, la qualité et la rapidité des interventions en maintenance deviennent des éléments clés. Pour conserver leur compétitivité, les industriels recherchent activement des solutions pour améliorer l'efficacité et la productivité des opérations de maintenance tout en préservant un très haut niveau de sécurité. L'objectif du projet est de permettre à un opérateur de maintenance, sur des terminaux mobiles de type smartphone, tablette, casque ou lunette, de disposer d'une information parfaitement contextualisée à la situation opérationnelle dans laquelle il se trouve (visualiser sur des documents, notices ou des schémas techniques, interagir avec un expert distant, se connecter à un système d'information…). Cette étude à orientation prospective propose, à partir d'une approche ergonomique centrée sur les usages (observations in situ, entretiens semi-dirigés, analyse cognitivo-discursive-ACD-, caractérisation des besoins), d'identifier un panel de nouvelles technologies d'interaction répondant aux besoins des opérateurs, aux exigences industrielles et pouvant s'adapter à des environnements opérationnels contraints.

International audience; RESUME L'Ocean Living Lab (OLL) est le premier Living lab européen dédié à l'océan, la glisse, au nautisme et aux sports aquatiques. L'objectif de OLL est de réaliser des tests fiables sur de nouveaux matériels et d'analyser les besoins des utilisateurs. Dans cette optique, une expérimentation centrée utilisateur a été menée avec des outils classiquement utilisés en Ergonomie et Ingénierie Facteurs Humains afin de tester une pirogue prototype, de comparer ses performances à celles de trois autres modèles existants, et d'apprécier son acceptabilité. Lors de tests menés sur un lac, six participants pratiquant la pirogue à haut niveau ont eu à effectuer un parcours balisé de 500 mètres en utilisant respectivement les quatre pirogues proposées et en respectant des consignes classiques d'entraînement. Les conditions environnementales et météorologiques (température, humidité, variations de la vitesse et de la direction du vent), ainsi que les oscillations du matériel sur l'eau ont été recueillies. Pour les participants, différents dispositifs ont permis de relever pendant les tests : postures, mouvements, fréquences cardiaques, temps, et en post-test leur ressenti. L'analyse des données multidimensionnelles montre que la pirogue-cible est aussi performante que les autres et que ce nouveau concept, très bien apprécié, répond aux besoins des utilisateurs. ABSTRACT The Ocean Living Lab (OLL) is the first European Living Lab dedicated to the ocean, sliding, boating and water sports. OLL's goal is to perform reliable testing on new hardware and analyze user needs. With this in mind, a user-centered experiment was conducted with tools conventionally used in Ergonomics and Human Factors Engineering to test a prototype canoe, compare its performance with those of three other existing models, and appreciate its acceptability. During tests carried out on a lake, six subjects practicing the high level canoe had to make a marked course of 500 meters using respectively the four canoes proposed and respecting conventional training instructions. Environmental and meteorological conditions (temperature, humidity, changes in wind speed and direction) and the swings of the material on the water were collected. For the subjects, various devices made it possible to note during the tests: postures, movements, cardiac frequencies, time, and in post-test their felt. The analysis of multidimensional data shows that the target canoe is as efficient as the others and that this new concept, very well appreciated, meets the needs of users.

International audience

International audience; Fetal and neonatal exposure to long chain alkylphenols has been suspected to promote breast developmental disorders and consequently to increase breast cancer risk. However, disease predisposition from developmental exposures remains unclear. In this work, human MCF-10A mammary epithelial cells were exposed in vitro to a low dose of a realistic [4-nonylphenol+4-tert-octylphenol] mixture. Transcriptome and cell phenotype analyses combined to functional and signaling network modeling indicated that long chain alkylphenols triggered enhanced proliferation, migration ability and apoptosis resistance and shed light on the underlying molecular mechanisms which involved the human estrogen receptor variant ERα36. A male mouse inherited transgenerational model of exposure to 3 environmentally relevant doses of the alkylphenol mix was set up in order to determine whether and how it would impact on mammary gland architecture. Mammary glands from F3 progeny obtained after intrabuccal chronic exposure of C57BL/6J P0 pregnant mice followed by F1 to F3 male inheritance displayed an altered histology which correlated with the phenotypes observed in vitro in human mammary epithelial cells. Since cellular phenotypes are similar in vivo and in vitro and involve the unique ERα36 human variant, such consequences of alkylphenol exposure could be extrapolated from mouse model to human. However, transient alkylphenol treatment combined to ERα36 overexpression in mammary epithelial cells were not sufficient to trigger tumorigenesis in xenografted Nude mice. Therefore, it remains to be determined if low dose alkylphenol transgenerational exposure and subsequent abnormal mammary gland development could account for an increased breast cancer susceptibility.

National audience

Présentation Poster; International audience; Estrogen receptor alpha 36 (ERα36) is a variant of the canonical estrogen receptor alpha (ERα66), whose high expression level correlates with a poor survival prognosis for breast cancer patients. While our previous results indicated that a high ERα36 expression level correlates with hormone independent growth and enhanced metastatic potential (Chamard-Jovenin et al, 2015; doi: 10.1186/s12918-015-0178-7) the mechanisms of ERα36 expression onset and the consequences for the normal mammary gland are poorly documented. Therefore, we explored (i) the methylation status of ERα36 promoter in 60 mammary tumor samples and (ii) the consequences of a ERα36 overexpression in vitro in MCF-10A normal mammary epithelial cells and in vivo in a unique model of MMTV-ERα36 transgenic mouse strain wherein the human ERα36 mRNA was specifically expressed in the mammary gland. Our data indicate a marked correlation between promoter methylation and ERα36 expression. Concomitantly, ERα36 overexpression lowered proliferation rate but enhanced migration and survival of the MCF-10A cell line. By a combination of bioinformatics and computational analyses of microarray data, we identified hierarchical gene networks, downstream of ERα36. In vivo, human ERα36 expression led to duct epithelium thinning and E-cadherin expression loss in adult but not prepubescent mice. Here, we show that ERα36 expression could be driven, at least in part, by epigenetic mechanisms. Moreover, an enhanced expression of ERα36 is sufficient, by itself, to disrupt normal breast epithelial phenotype in vivo and in vitro through a dominant-positive effect on nongenomic estrogen signaling pathways. These results also suggest that, in the presence of endogenous estradiol, ERα36 overexpression in vivo contributes to alter mammary gland architecture which may support pre-neoplastic lesion and augment breast cancer risk.

International audience

International audience; Growing source of evidence suggests that exposure to estrogen mimicking agents is a risk factor for breast cancer onset and progression. Long chain alkylphenols are man made compounds still present in household products, industrial and agricultural processes, leading to a global environmental and human contamination. These molecules are known to exert estrogen -like activities through binding to classical estrogen receptors. Recently, we have demonstrated that a realistic mixture of 4 tert - octylphenol and 4 - nonylphenol can stimulate proliferation and modulate epigenetic status of testicular cancer germ cells through a rapid, Estrogen Receptor alpha 36 (ERα36) -dependent non genomic pathway (Ajj et al, 2013; doi: 10.1371/journal.pone.0061758). In a retrospective study of breast tumor samples, we also validated ERα36 expression as a reliable prognostic factor for cancer progression from an estrogen dependent prolifera tive tumor toward an estrogen dispensable metastatic disease (Chamard - Jovenin et al, 2015; doi: 10.1186/s12918 - 015 - 0178 - 7). Since high ERα36 expression enhances expression of migration/invasion markers in breast tumors, we addressed the question of its involvement in response to alkylphenol exposure in vitro (MCF -10A mammary epithelial cell line and MCF -7 estrogen -sensitive cancer cells) and in vivo ( C57BL mice). A male inherited transgenerational model of exposure to environmentally relevant doses of an alkylphenol mix was set up in C57BL/6J mice to determine whether and how it impacts on mammary gland morphogenesis. Human mammary epithelial MCF -10A cells were exposed to similar doses to decipher the molecular mechanisms involved by a combination of transcriptomic study, cell phenotype analyses, functional and signaling network modeling. The relevance of mouse phenotype extrapolation to human risk is discussed. Mouse mammary gland exposed transgenerationally to the alkylphenol mix displayed a neoplastic -like histology. This phenotype was correlated with the enhanced proliferation, migration ability and apoptosis resistance observed in vitro on human mammary epithelial cells and mediated by the estrogen receptor variant ERα36. Since cellular phenotypes are similar in vivo and in vitro and involve the unique ERα36 human variant , such consequences of alkylphenol exposure could be extrapolated from mouse model to human. Low dose alkylphenol transgenerational exposure could promote abnormal mammary gland development and subsequently increase the risk of breast cancer at ageing.

Présentation Poster; National audience; Growing source of evidence suggests that exposure to estrogen mimicking agents is a risk factor for breast cancer onset and progression. Long chain alkylphenols are man-made compounds still present in household products, industrial and agricultural processes, leading to a global environmental and human contamination. These molecules are known to exert estrogen-like activities through binding to classical estrogen receptors. Recently, we have demonstrated that a realistic mixture of 4-tert-octylphenol and 4-nonylphenol can stimulate proliferation and modulate epigenetic status of testicular cancer germ cells through a rapid, Estrogen Receptor alpha 36 (ERα36)- dependent non genomic pathway (Ajj et al, 2013; doi: 10.1371/journal.pone.0061758). In a retrospective study of breast tumor samples, we also validated ERα36 expression as a reliable prognostic factor for cancer progression from an estrogen dependent proliferative tumor toward an estrogen dispensable metastatic disease (Chamard-Jovenin et al, 2015; doi: 10.1186/s12918-015-0178-7). Since high ERα36 expression enhances expression of migration/invasion markers in breast tumors, we addressed the question of its involvement in response to alkylphenol exposure in vitro (MCF-10A mammary epithelial cell line and MCF-7 estrogen-sensitive cancer cells) and in vivo (C57/Bl6 mice). MethodsIn order to characterize the molecular events in alkylphenol exposed cells, ERα36 overexpression (knock in) or gene-silencing (knock down) strategies combined to microarray analyses of the mixture target genes were used in MCF-10A cells. Molecular and cellular biology experiments confirmed the predicted phenotypes. A customized database was designed to analyze comprehensive gene expression results, nonlinear correlation analyses, and mutual information computations helpful for the modeling of alkylphenol/ERα36-dependent pathways.In vivo, alkylphenol mixture doses, representative of human exposure, were orally given to C57/Bl6 pregnant females and histological analyses were then performed on F1 mammary glands. Key ResultsOur results highlight a key role for ERa36 in alkylphenol non genomic src protein kinase /PI3-kinase/serine-threonine kinase Akt/ nuclear factor-kappa B signaling in non cancerous epithelial breast cells. Flow cytometry analyses, scratch-wound assays and caspase clivage measurements indicate that the alkylphenol mixture may promote a neoplastic like phenotype, i. e. proliferation, apoptosis escape and migration in MCF-10A epithelial cells through an ERα36 dependent pathway. These results are currently used to build a model of alkylphenol-directed breast cancer induction and progression. In vivo, mammary gland hyperplasia is observed following alkylphenol exposure during embryonic life. ConclusionsHence, alkylphenol and/or ERa36-dependent control of the proliferation, adhesion and survival pathways opens the way to a better understanding of the link between endocrine disruptor exposure and the burden of hormone sensitive cancers. This work is supported by ANSES (n°2012-2-014).

Présentation Poster; National audience

National audience

Présentation Poster; International audience