Quelle R&D Mener pour le Développement Des Réseaux D'énergie De Demain ? Les Propositions de L'ancre en 2015

Feuille de route sur les réseaux électriques et stockage élaborée par le GP10 Réseaux et Stockages de l'Energie de l'ANCRECette feuille de route concerne les réseaux d’énergie électrique, de chaleur et de froid, les réseaux de gaz (hydrogène, gaz naturel), leurs stockages associés, ainsi que leurs couplages à venir dans le cadre de la transition énergétique et des évolutionsqui l’accompagneront, que ce soit sur les modes de production d’énergie ou sur l’évolution des usages.Le focus est porté sur les réseaux électriques qui seront les premiers impactés par cette transition énergétique. Hormisquelques éléments très spécifiques aux réseaux électriques (et qui seront notés dans le texte par une couleur différente)il est à souligner que la quasi-totalité des considérations et axes de R&D évoqués pour les réseauxélectriques et le développement de leur « intelligence » et/ou de leur flexibilité s’appliquentégalement aux autres réseaux d’énergie. Par ailleurs, si le groupe programmatique« Réseaux et Stockage » de l’ANCRE (GP10) s’est largement appuyé sur les nombreuses feuilles de route émises tant au niveau national, dont celles de l’ADEME, qu’européen, il a également souhaité s’en démarquer en insistantlargement et en détaillant les recherches scientifiques et technologiques à mener face aux verrous actuellement identifiés

Sporadic Infantile Epileptic Encephalopathy Caused by Mutations in PCDH19 Resembles Dravet Syndrome but Mainly Affects Females

Dravet syndrome (DS) is a genetically determined epileptic encephalopathy mainly caused by de novo mutations in the SCN1A gene. Since 2003, we have performed molecular analyses in a large series of patients with DS, 27% of whom were negative for mutations or rearrangements in SCN1A. In order to identify new genes responsible for the disorder in the SCN1A-negative patients, 41 probands were screened for micro-rearrangements with Illumina high-density SNP microarrays. A hemizygous deletion on chromosome Xq22.1, encompassing the PCDH19 gene, was found in one male patient. To confirm that PCDH19 is responsible for a Dravet-like syndrome, we sequenced its coding region in 73 additional SCN1A-negative patients. Nine different point mutations (four missense and five truncating mutations) were identified in 11 unrelated female patients. In addition, we demonstrated that the fibroblasts of our male patient were mosaic for the PCDH19 deletion. Patients with PCDH19 and SCN1A mutations had very similar clinical features including the association of early febrile and afebrile seizures, seizures occurring in clusters, developmental and language delays, behavioural disturbances, and cognitive regression. There were, however, slight but constant differences in the evolution of the patients, including fewer polymorphic seizures (in particular rare myoclonic jerks and atypical absences) in those with PCDH19 mutations. These results suggest that PCDH19 plays a major role in epileptic encephalopathies, with a clinical spectrum overlapping that of DS. This disorder mainly affects females. The identification of an affected mosaic male strongly supports the hypothesis that cellular interference is the pathogenic mechanism

Underrepresentation of Elderly People in Randomised Controlled Trials. The Example of Trials of 4 Widely Prescribed Drugs

BACKGROUND: We aimed to determine the representation of elderly people in published reports of randomized controlled trials (RCTs). We focused on trials of 4 medications--pioglitazone, rosuvastatin, risedronate, and valsartan-frequently used by elderly patients with chronic medical conditions. METHODS AND FINDINGS: We selected all reports of RCTs indexed in PubMed from 1966 to April 2008 evaluating one of the 4 medications of interest. Estimates of the community-based "on-treatment" population were from a national health insurance database (SNIIR-AM) covering approximately 86% of the population in France. From this database, we evaluated data claims from January 2006 to December 2007 for 1,958,716 patients who received one of the medications of interest for more than 6 months. Of the 155 RCT reports selected, only 3 studies were exclusively of elderly patients (2 assessing valsartan; 1 risedronate). In only 4 of 37 reports (10.8%) for pioglitazone, 4 of 22 (18.2%) for risedronate, 3 of 29 (10.3%) for rosuvastatine and 9 of 67 (13.4%) for valsartan, the proportion of patients aged 65 or older was within or above that treated in clinical practice. In 62.2% of the reports for pioglitazone, 40.9% for risedronate, 37.9% for rosuvastatine, and 70.2% for valsartan, the proportion of patients aged 65 or older was lower than half that in the treated population. The representation of elderly people did not differ by publication date or sample size. CONCLUSIONS: Elderly patients are poorly represented in RCTs of drugs they are likely to receive

NQO1-Dependent Redox Cycling of Idebenone: Effects on Cellular Redox Potential and Energy Levels

Short-chain quinones are described as potent antioxidants and in the case of idebenone have already been under clinical investigation for the treatment of neuromuscular disorders. Due to their analogy to coenzyme Q10 (CoQ10), a long-chain quinone, they are widely regarded as a substitute for CoQ10. However, apart from their antioxidant function, this provides no clear rationale for their use in disorders with normal CoQ10 levels. Using recombinant NAD(P)H:quinone oxidoreductase (NQO) enzymes, we observed that contrary to CoQ10 short-chain quinones such as idebenone are good substrates for both NQO1 and NQO2. Furthermore, the reduction of short-chain quinones by NQOs enabled an antimycin A-sensitive transfer of electrons from cytosolic NAD(P)H to the mitochondrial respiratory chain in both human hepatoma cells (HepG2) and freshly isolated mouse hepatocytes. Consistent with the substrate selectivity of NQOs, both idebenone and CoQ1, but not CoQ10, partially restored cellular ATP levels under conditions of impaired complex I function. The observed cytosolic-mitochondrial shuttling of idebenone and CoQ1 was also associated with reduced lactate production by cybrid cells from mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) patients. Thus, the observed activities separate the effectiveness of short-chain quinones from the related long-chain CoQ10 and provide the rationale for the use of short-chain quinones such as idebenone for the treatment of mitochondrial disorders

A Systems Biology Approach Reveals the Role of a Novel Methyltransferase in Response to Chemical Stress and Lipid Homeostasis

Using small molecule probes to understand gene function is an attractive approach that allows functional characterization of genes that are dispensable in standard laboratory conditions and provides insight into the mode of action of these compounds. Using chemogenomic assays we previously identified yeast Crg1, an uncharacterized SAM-dependent methyltransferase, as a novel interactor of the protein phosphatase inhibitor cantharidin. In this study we used a combinatorial approach that exploits contemporary high-throughput techniques available in Saccharomyces cerevisiae combined with rigorous biological follow-up to characterize the interaction of Crg1 with cantharidin. Biochemical analysis of this enzyme followed by a systematic analysis of the interactome and lipidome of CRG1 mutants revealed that Crg1, a stress-responsive SAM-dependent methyltransferase, methylates cantharidin in vitro. Chemogenomic assays uncovered that lipid-related processes are essential for cantharidin resistance in cells sensitized by deletion of the CRG1 gene. Lipidome-wide analysis of mutants further showed that cantharidin induces alterations in glycerophospholipid and sphingolipid abundance in a Crg1-dependent manner. We propose that Crg1 is a small molecule methyltransferase important for maintaining lipid homeostasis in response to drug perturbation. This approach demonstrates the value of combining chemical genomics with other systems-based methods for characterizing proteins and elucidating previously unknown mechanisms of action of small molecule inhibitors

Scrub typhus ecology: a systematic review of Orientia in vectors and hosts

Abstract Scrub typhus, caused by Orientia tsutsugamushi, is an important and neglected vector-borne zoonotic disease with an expanding known distribution. The ecology of the disease is complex and poorly understood, impairing discussion of public health interventions. To highlight what we know and the themes of our ignorance, we conducted a systematic review of all studies investigating the pathogen in vectors and non-human hosts. A total of 276 articles in 7 languages were included, with 793 study sites across 30 countries. There was no time restriction for article inclusion, with the oldest published in 1924. Seventy-six potential vector species and 234 vertebrate host species were tested, accounting for over one million trombiculid mites (‘chiggers’) and 83,000 vertebrates. The proportion of O. tsutsugamushi positivity was recorded for different categories of laboratory test and host species. Vector and host collection sites were geocoded and mapped. Ecological data associated with these sites were summarised. A further 145 articles encompassing general themes of scrub typhus ecology were reviewed. These topics range from the life-cycle to transmission, habitats, seasonality and human risks. Important gaps in our understanding are highlighted together with possible tools to begin to unravel these. Many of the data reported are highly variable and inconsistent and minimum data reporting standards are proposed. With more recent reports of human Orientia sp. infection in the Middle East and South America and enormous advances in research technology over recent decades, this comprehensive review provides a detailed summary of work investigating this pathogen in vectors and non-human hosts and updates current understanding of the complex ecology of scrub typhus. A better understanding of scrub typhus ecology has important relevance to ongoing research into improving diagnostics, developing vaccines and identifying useful public health interventions to reduce the burden of the disease.</jats:p

Revised Morning Loops of the Arabidopsis Circadian Clock Based on Analyses of Direct Regulatory Interactions

The network structure of the plant circadian clock is complex and direct regulatory interactions between individual components have proven particularly difficult to predict from genetic analyses. Here, we systematically investigate in vivo binding interactions between the morning-specific transcription factor, LATE ELONGATED HYPOCOTYL (LHY) and the promoters of other components of the network. We then demonstrate the functionality of these interactions by testing the responsiveness of the target gene to an ethanol-induced change in expression level of the LHY protein. We uncover novel, negative autoregulatory feedback loops from LHY and the closely related CIRCADIAN CLOCK ASSOCIATED-1 (CCA1) onto their own and each other’s expression. Furthermore we show that LHY acts as a repressor of all other clock components, including PSEUDO-RESPONSE REGULATORs (PRRs) 9 and 7, which were previously thought to be positive regulatory targets. These experimental results lead to a substantial revision of the morning loops of the clock

Contacts et acculturations en Méditerranée occidentale

La question des contacts entre les différents peuples qui bordent les rives de la Méditerranée nord occidentale est l’un des sujets phares de la recherche archéologique de ces trente dernières années. Que l’on parle d’époque archaïque et classique ou de Protohistoire et d’âge du Fer, les échanges et les processus d’acculturation de ces peuples qui entrèrent alors en contact les uns avec les autres : Grecs, Celtes, Phéniciens, Ibères, Ligures, Étrusques, ont retenu l’attention des chercheurs travaillant sur l’expansion grecque dans ces régions, sur les trafics commerciaux, sur les échanges culturels. L’œuvre de Michel Bats (Directeur de recherche honoraire du CNRS) traverse toutes ces thématiques : la présence des Phocéens et des Étrusques dans le bassin occidental de la Méditerranée, l’acculturation et les identités ethno-culturelles, les recherches sur la céramique et ses usages dans une perspective anthropologique, l’appropriation de l’écriture par les sociétés protohistoriques. Ses collègues et amis, en organisant ce colloque et en participant à ces actes, entendent lui témoigner leur amitié et leur dette intellectuelle. Ce volume réunit des articles des meilleurs spécialistes, actuels de la question - des chercheurs de toute la Méditerranée - autour des quatre grands thèmes que nous venons d’évoquer afin tout à la fois de dresser un bilan et de définir de nouvelles perspectives. Cet ouvrage présente donc aussi bien des synthèses - sur la présence grecque en Espagne, sur l’origine de l’écriture, sur les pratiques funéraires, sur les identités culturelles et ethniques - que des découvertes récentes concernant la thématique des contacts et de l’acculturation en Méditerranée nord occidentale : l’agglomération du Premier âge du Fer de La Cougourlude (Lattes, Hérault) fouillée durant l’été 2010 ; le sanctuaire hellénistique de Cumes et les fouilles récentes de Fratte en Italie ; les ateliers de potiers de Rosas en Espagne ; les dernières découvertes d’Olbia de Provence

Grecs et Etrusques à Lattes : nouvelles données à partir des fouilles de la Cougourlude

International audienc

Littérature scène et musique dans les œuvres scéniques de Benjamin Britten

Les opéras de Benjamin Britten témoignent de l engagement de leur auteur pour le renouveau de la scène et de la dramaturgie au XXe siècle. Par son travail avec l avant-garde théâtrale (musique de scène, drame radiophonique, musique pour films documentaires), Britten a su se nourrir des innovations marquantes du début du siècle, se révélant alors un formidable passeur des théories et esthétiques dramatiques de cette période. Si ses oeuvres lyriques sont le lieu où cet apprentissage est mis en pratique, elles proposent et expérimentent également de nouvelles dramaturgies scéniques. La dramaturgie brittenienne n a pas laissé le public indifférent : vivement appréciée des grands metteurs en scène européens, elle bouscula les Français dans leurs habitudes et leurs a priori face à la musique anglaise.Benjamin Britten s operas are witness to their author's commitment to a renewal of the stage and dramaturgy in the 20th century. Through working with the theatrical avant-garde (stage music, radio dramas, music for documentary films), Britten knew how to take advantage of the outstanding innovations of the beginning of the century, becoming a wonderful conduit of the theories and dramatic aesthetics of that period. While he put this apprenticeship into practice in his lyric works, these works also suggest and experiment with new scenic dramatic arts. Britten's dramaturgy did not leave the public indifferent; keenly appreciated by the great European theatre directors, it jostled the French out of their habits and their prejudices against English music.TOURS-Bibl.électronique (372610011) / SudocSudocFranceF