A BAYESIAN GRAPHICAL MODELING APPROACH TO MICRORNA REGULATORY NETWORK INFERENCE

It has been estimated that about 30% of the genes in the human genome are regulated by microRNAs (miRNAs). These are short RNA sequences that can down-regulate the levels of mRNAs or proteins in animals and plants. Genes regulated by miRNAs are called targets. Typically, methods for target prediction are based solely on sequence data and on the structure information. In this paper we propose a Bayesian graphical modeling approach that infers the miRNA regulatory network by integrating expression levels of miRNAs with their potential mRNA targets and, via the prior probability model, with their sequence/structure information. We use a directed graphical model with a particular structure adapted to our data based on biological considerations. We then achieve network inference using stochastic search methods for variable selection that allow us to explore the huge model space via MCMC. A time-dependent coefficients model is also implemented. We consider experimental data from a study on a very well-known developmental toxicant causing neural tube defects, hyperthermia. Some of the pairs of target gene and miRNA we identify seem very plausible and warrant future investigation. Our proposed method is general and can be easily applied to other types of network inference by integrating multiple data sources.Comment: Published in at http://dx.doi.org/10.1214/10-AOAS360 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Evaluation of 309 Environmental Chemicals Using a Mouse Embryonic Stem Cell Adherent Cell Differentiation and Cytotoxicity Assay

The vast landscape of environmental chemicals has motivated the need for alternative methods to traditional whole-animal bioassays in toxicity testing. Embryonic stem (ES) cells provide an in vitro model of embryonic development and an alternative method for assessing developmental toxicity. Here, we evaluated 309 environmental chemicals, mostly food-use pesticides, from the ToxCast™ chemical library using a mouse ES cell platform. ES cells were cultured in the absence of pluripotency factors to promote spontaneous differentiation and in the presence of DMSO-solubilized chemicals at different concentrations to test the effects of exposure on differentiation and cytotoxicity. Cardiomyocyte differentiation (α,β myosin heavy chain; MYH6/MYH7) and cytotoxicity (DRAQ5™/Sapphire700™) were measured by In-Cell Western™ analysis. Half-maximal activity concentration (AC50) values for differentiation and cytotoxicity endpoints were determined, with 18% of the chemical library showing significant activity on either endpoint. Mining these effects against the ToxCast Phase I assays (∼500) revealed significant associations for a subset of chemicals (26) that perturbed transcription-based activities and impaired ES cell differentiation. Increased transcriptional activity of several critical developmental genes including BMPR2, PAX6 and OCT1 were strongly associated with decreased ES cell differentiation. Multiple genes involved in reactive oxygen species signaling pathways (NRF2, ABCG2, GSTA2, HIF1A) were strongly associated with decreased ES cell differentiation as well. A multivariate model built from these data revealed alterations in ABCG2 transporter was a strong predictor of impaired ES cell differentiation. Taken together, these results provide an initial characterization of metabolic and regulatory pathways by which some environmental chemicals may act to disrupt ES cell growth and differentiation

Projects as learning agency at organization borders:a resource for organization learning ?

International audienc

Insectes des stocks de blé, 95 silos à la loupe: Charançons, capucins, tribolium et silvains ? Insecticides, balai, aspirateur et tamis... ce qu'en dit l'enquête EcoprotectGrain

National audienceDans le cadre du projet CasDar « EcoprotectGrain » inscrit dans le chantier 4 du RMT Quasaprove, une enquête a été réalisée en 2010 dans 95 sites de stockage de blé tendre français. Des analyses d'échantillons de grains prélevés dans des zones à risque d'insectes, il ressort: - la présence du charançon du riz dans un quart des échantillons, le charançon du blé semblant régresser par rapport aux enquêtes précédentes réalisées en 1977 et 1978 ; - la présence du capucin des grains, absent lors des enquêtes précédentes ; - la faculté d'insectes réputés sans « formes cachées » de se cacher quand même ; - la présence de résidus d'insecticides de stockage dans les 2/3 des échantillons, mais toujours en dessous de leurs LMR ; - plusieurs facteurs diminuant l'incidence desinsectes: le stockage vertical (parrapport à celui à plat), la présence de thermométrie fixe (sans effet direct mais indice de site bien équipé), le nettoyage physique complet des cellules vides et celui du grain (séparation des impuretés). L'enquête se poursuit en 2011 afin de vérifier les tendances signalées, en préciser d'autres et afin d'aider à définir des itinéraires de bonnes pratiques de préservation des grains

Removal of seminal plasma enhances membrane stability on fresh and cooled stallion spermatozoa

Contents Fertility is reduced after semen cooling for a considerable number of stallions. The main hypotheses include alterations in plasma membrane following cooling and deleterious influence of seminal plasma. However, interindividual variability is controversial. We hypothesized that the removal of seminal plasma could enhance motility in some poor cooler stallions, but could also affect, negatively or positively, membrane quality in some stallions. This study examined the effect of centrifugation, followed or not by removal of seminal plasma, on parameters indicating semen quality after 48 h at 4 degrees C: motility, plasma membrane integrity as evaluated by hypo-osmotic swelling test, acrosome integrity and response to a pharmacological induction of acrosome reaction using ionophore A23187. Sixty-six ejaculates from 14 stallions were used, including stallions showing high or low sperm motility after cooled storage. Centrifugation without removal of seminal plasma did not affect sperm parameters. Removal of seminal plasma did not affect motility, but significantly stabilized sperm membranes, as demonstrated by a higher response to the osmotic challenge, and a reduced reactivity of the acrosome. Moreover, for the same semen sample, the response to an induction of acrosome reaction was significantly higher when the induction was performed in the presence of seminal plasma, compared with the induction in the absence of seminal plasma. This was observed both for fresh and cooled semen. When the induction of acrosome reaction with ionophore A23187 is used to evaluate sperm quality, care must therefore be taken to standardize the proportion of seminal plasma between samples. For the 10 stallions serving at least 25 mares, the only variable significantly correlated with fertility was motility. The influence of membrane stabilization regarding fertility requires further investigations

Etude sur la conservation de la semence : Intérêt de l'utilisation de l'INRA96 et de la centrifugation

National audienc

Removal of seminal plasma by centrifugation, before cooled storage, enhances membrane stability of stallion spermatozoa

International audienc