A New Software Package for Predictive Gene Regulatory Network Modeling and Redesign

The efficacy of a newly created software package for predictive modeling of developmental gene regulatory networks (GRNs) has recently been demonstrated (Peter et al., 2012). The program GeNeTool computes spatial gene expression patterns based on GRN interactions and thereby allows the direct comparison of predicted and observed spatial expression patterns. GeNeTool also permits in silico exploration of both cis- and trans- perturbations of GRN interactions. Here, we present this program, review briefly its major features and applications, and provide a detailed and accessible tutorial

The sizes of the exchangeable pools of selenium in elderly women and their relation to institutionalization

Exchangeable pools of Se after an intravenous injection of 74Se-enriched isotope as sodium selenite were measured in two groups (n 9) of elderly women (free-living aged 64-82 years and institutionalized aged 68-82 years), and a comparison group (n 9) of young women aged 31-40 years to evaluate the effect of age and institutionalization on Se reserves. Dietary Se intake was not different among the three groups. Plasma Se and glutathione peroxidase (EC 1.11.1.9) levels were significantly lower in the institutionalized elderly women (P < 0.05). In each of the three groups, two pools were determined from our model. The size of the first pool and the sum of the two pools were lower in the group of institutionalized elderly women than in the other two groups. The significant correlation between plasma Se level and total Se pool size (r 0.66, P < 0.01) indicated that this last variable could serve as a new marker of Se status. Finally, these data suggest that the Se status of elderly women is more related to lifestyle, in terms of institutionalization or not, than to age per s

In Subfertile Couple, Abdominal Fat Loss in Men Is Associated with Improvement of Sperm Quality and Pregnancy: A Case-Series

International audienceBackground: The impact of overweight among men of reproductive-age may affect fertility. Abdominal fat, more than body mass index, is an indicator of higher metabolic risk, which seems to be involved in decreasing sperm quality. This study aims to assess the relationship between abdominal fat and sperm DNA fragmentation and the effect of abdominal fat loss, among 6 men in subfertile couples. Methods: Sperm DNA fragmentation, abdominal fat and metabolic and hormonal profiles were measured in the 6 men before and after dietary advices. Seminal oxidative stress and antioxidant markers were determined. Results: After several months of a lifestyle program, all 6 men lost abdominal fat (patient 1: loss of 3 points of abdominal fat, patient 2: loss of 3 points, patient 3: loss of 2 points, patient 4: loss of 1 point, patient 5: loss of 4 points and patient 6: loss of 13 points). At the same time, their rate of sperm DNA fragmentation decreased: 9.5% vs 31%, 24% vs 43%, 18% vs 47%, 26.3% vs 66%, 25.4% vs 35% and 1.7% vs 25%. Also, an improvement in both metabolic (significant decrease in triglycerides and total cholesterol; p = 0.0139) and hormonal (significant increase in testosterone/oestradiol ratio; p = 0.0139) blood profiles was observed after following the lifestyle program. In seminal plasma, the amount of SOD2 has significantly increased (p = 0.0139) while in parallel carbonylated proteins have decreased. Furthermore, all spouses got pregnant. All pregnancies were brought to term. Conclusion: This study shows specifically that sperm DNA fragmentation among men in subfertile couples could be affected by abdominal fat, but improvement of lifestyle factor may correct this alteration. The effect of specific abdominal fat loss on sperm quality needs further investigation. The reduction of oxidative stress may be a contributing factor

A dietary supplementation with leucine and antioxidants is capable to accelerate muscle mass recovery after immobilization in adult rats

Prolonged inactivity induces muscle loss due to an activation of proteolysis and decreased protein synthesis; the latter is also involved in the recovery of muscle mass. The aim of the present work was to explore the evolution of muscle mass and protein metabolism during immobilization and recovery and assess the effect of a nutritional strategy for counteracting muscle loss and facilitating recovery. Adult rats (6-8 months) were subjected to unilateral hindlimb casting for 8 days (10-18) and then permitted to recover for 10 to 40 days (R10-R40). They were fed a Control or Experimental diet supplemented with antioxidants/polyphenols (AOX) (10 to 18), AOX and leucine (AOX + LEU) (18 to R15) and LEU alone (R15 to R40). Muscle mass, absolute protein synthesis rate and proteasome activities were measured in gastrocnemius muscle in casted and non-casted legs in post prandial (PP) and post absorptive (PA) states at each time point. Immobilized gastrocnemius protein content was similarly reduced (-37%) in both diets compared to the non-casted leg. Muscle mass recovery was accelerated by the AOX and LEU supplementation (+6% AOX+LEU vs. Control, P<0.05 at R40) due to a higher protein synthesis both in PA and PP states (+23% and 31% respectively, Experimental vs. Control diets, P<0.05, R40) without difference in trypsin-and chymotrypsin-like activities between diets. Thus, this nutritional supplementation accelerated the recovery of muscle mass via a stimulation of protein synthesis throughout the entire day (in the PP and PA states) and could be a promising strategy to be tested during recovery from bed rest in humans

Evaluation de l'impact de la recherche au Cirad : Rapport du groupe de travail

Un groupe de travail réunissant des experts du Cirad, de l'AFD, de l'INRA et de l'IRD a étudié les conditions d'application de l'évaluation de l'impact de la recherche au Cirad. A partir d'exemples pris essentiellement dans le domaine de la recherche agricole internationale, le groupe définit la sémantique de l'évaluation de l'impact et décrit la démarche à entreprendre pour comprendre le " chemin de l'impact ". Il met en évidence la difficulté d'attribuer un changement à une action précise, l'importance des délais entre action et changement, les contraintes liées à la prise en compte d'un référentiel témoin (le " contrefactuel "), les controverses qu'accompagne la mesure économique des impacts, notamment lorsqu'il s'agit de biens non marchands, la sous-estimation fréquente des effets négatifs. Il prend connaissance d'approches alternatives basées davantage sur l'analyse des liens entre action et changement que sur la mesure de l'efficacité. Il met en avant la nécessité de définir les attendus des études d'évaluation de l'impact avant de s'engager dans la démarche. Les évaluations d'impact sont devenues une norme dans la gouvernance de la recherche internationale. Des compétences individuelles existent parmi les chercheurs du Cirad et l'expérience d'une première initiative interne au début des années 2000 est riche d'enseignements. Il est prévisible que les politiques de recherche et développement technologique françaises et européennes vont évoluer vers une plus grande prise en compte des relations entre la science et la société. Le comité d'éthique recommande au Cirad de s'engager dans l'évaluation d'impact. Le groupe de travail recommande donc que le Cirad, acteur des processus d'innovation au Sud, s'engage dans l'aventure de l'évaluation de l'impact pour mieux savoir quels changements son action induit en prenant en considération les écueils possibles de la démarche. Le groupe de travail propose 3 objectifs à la démarche du Cirad : i) Caractériser et repérer les effets retirés des investissements du Cirad vis-à-vis des enjeux majeurs de sa stratégie. ii) Comprendre comment les impacts sont générés, quels facteurs les déterminent et contribuer ainsi à améliorer l'efficacité du processus de recherche et d'innovation. iii) Informer la société, les décideurs, les partenaires des effets induits par les travaux du CIRAD. Cette démarche interroge en outre le sens de l'activité du Cirad, de ses chercheurs, et participe à l'écriture de son histoire scientifique. Elle complète le dispositif actuel d'évaluation mis en place aux échelles de l'établissement, des unités de recherche et des chercheurs. Elle peut outiller les unités de recherche pour mettre en oeuvre une recherche mieux finalisée. La démarche à entreprendre présentée par le groupe de travail vise à rechercher les changements liés aux actions du Cirad dans l'ensemble des sphères sociales, économiques, environnementales, scientifiques, politiques. Elle précise la nature des sujets à retenir : une innovation, une production, un secteur de recherche, un dispositif, un projet, etc. Le groupe propose de commencer la démarche en mobilisant en priorité des compétences internes. Après avoir sensibilisé les unités de recherche aux objectifs de la démarche et en recherchant celles qui seraient volontaires pour s'engager dans l'analyse d'une première série de sujets, cinq études de cas ont été retenues : i) production de nouvelles variétés hybrides de café ; ii) contrôle de la peste des petits ruminants (PPR) au Maroc ; iii) filière mangue en Afrique Sub-saharienne ; iv) projet européen Fonio ; v) recherches sur le conseil à l'exploitation familiale. Des sousgroupes associant membres du groupe de travail et chercheurs des unités de recherche concernés par ces sujets ont décrit la chaîne causale entre investissements, résultats de recherche et changements observés. Le tableau 3 compare les cas1. Le groupe de travail tire les premiers enseignements des comptes-rendus faits par ces sou

Predictive computation of genomic logic processing functions in embryonic development

Gene regulatory networks (GRNs) control the dynamic spatial patterns of regulatory gene expression in development. Thus, in principle, GRN models may provide system-level, causal explanations of developmental process. To test this assertion, we have transformed a relatively well-established GRN model into a predictive, dynamic Boolean computational model. This Boolean model computes spatial and temporal gene expression according to the regulatory logic and gene interactions specified in a GRN model for embryonic development in the sea urchin. Additional information input into the model included the progressive embryonic geometry and gene expression kinetics. The resulting model predicted gene expression patterns for a large number of individual regulatory genes each hour up to gastrulation (30 h) in four different spatial domains of the embryo. Direct comparison with experimental observations showed that the model predictively computed these patterns with remarkable spatial and temporal accuracy. In addition, we used this model to carry out in silico perturbations of regulatory functions and of embryonic spatial organization. The model computationally reproduced the altered developmental functions observed experimentally. Two major conclusions are that the starting GRN model contains sufficiently complete regulatory information to permit explanation of a complex developmental process of gene expression solely in terms of genomic regulatory code, and that the Boolean model provides a tool with which to test in silico regulatory circuitry and developmental perturbations

Fuzzy species limits in Mediterranean gorgonians (Cnidaria, Octocorallia): inferences on speciation processes

The study of the interplay between speciation and hybridization is of primary importance in evolutionary biology. Octocorals are ecologically important species whose shallow phylogenetic relationships often remain to be studied. In the Mediterranean Sea, three congeneric octocorals can be observed in sympatry: Eunicella verrucosa, Eunicella cavolini and Eunicella singularis. They display morphological differences and E.singularis hosts photosynthetic Symbiodinium, contrary to the two other species. Two nuclear sequence markers were used to study speciation and gene flow between these species, through network analysis and Approximate Bayesian Computation (ABC). Shared sequences indicated the possibility of hybridization or incomplete lineage sorting. According to ABC, a scenario of gene flow through secondary contact was the best model to explain these results. At the intraspecific level, neither geographical nor ecological isolation corresponded to distinct genetic lineages in E.cavolini. These results are discussed in the light of the potential role of ecology and genetic incompatibilities in the persistence of species limits.French National Research Agency (ANR) program Adacni (ANR) [ANR-12-ADAP-0016]CNRSHubert Curien 'Tassili' program [12MDU853]CCMAR Strategic Plan from Fundacao para a Ciencia e a Tecnologia-FCT [PEst-C/MAR/LA0015/2011,FEDERinfo:eu-repo/semantics/publishedVersio

Comparing Strategies for Coding Adjoints

This document presents and compares methodologies to generate discrete adjoint codes. These methods can be implemented when hand writing adjoints, or within Automatic Differentiation tools. Automatic differentiation has been applied successfully to industrial codes that are large and general enough to fully validate this new technology. Future AD tools will make use of some general methods presented in this paper but still not implemented within present tools. In this paper, we try to compare these strategies in terms of accuracy, execution time and memory requirement on a one dimension- al thermal-hydraulic module for two-phase flow modeling

GWAS in the SIGNAL/PHARE clinical cohort restricts the association between the FGFR2 locus and estrogen receptor status to HER2-negative breast cancer patients

International audienceGenetic polymorphisms are associated with breast cancer risk. Clinical and epidemiological observations suggest that clinical characteristics of breast cancer, such as estrogen receptor or HER2 status, are also influenced by hereditary factors. To identify genetic variants associated with pathological characteristics of breast cancer patients, a Genome Wide Association Study was performed in a cohort of 9365 women from the French nationwide SIGNAL/PHARE studies (NCT00381901/RECF1098). Strong association between the FGFR2 locus and ER status of breast cancer patients was observed (ER-positive n=6211, ER-negative n=2516; rs3135718 OR=1.34 p=5.46x10-12). This association was limited to patients with HER2-negative tumors (ER-positive n=4267, ER-negative n=1185; rs3135724 OR=1.85 p=1.16x10-11). The FGFR2 locus is known to be associated with breast cancer risk. This study provides sound evidence for an association between variants in the FGFR2 locus and ER status among breast cancer patients, particularly among patients with HER2-negative disease. This refinement of the association between FGFR2 variants and ER-status to HER2-negative disease provides novel insight to potential biological and clinical influence of genetic polymorphisms on breast tumors