53 research outputs found

    Lectures d’enfance et destinĂ©e chez Alain-Fournier

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    «Ne croyez pas que le Destinsoit plus que la densitĂ© de l’Enfance.» Rainer Maria Rilke Il est rare lorsqu’on Ă©tudie l’itinĂ©raire et l’Ɠuvre d’un Ă©crivain de se tourner vers les lectures qui nourrirent son enfance. Certes, faute de documents, la critique ne sait souvent rien d’elles. Mais ce n’est pas toujours le cas. En ce qui concerne les lectures d’enfance d’Alain-Fournier les tĂ©moignages abondent, riches, prĂ©cis: ceux du romancier lui-mĂȘme, de sa sƓur Isabelle ou encore de son meilleur ami..

    An insight into immunogenic salivary proteins of Anopheles gambiae in African children

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    <p>Abstract</p> <p>Background</p> <p>During blood feeding, the mosquito injects saliva into the vertebrate host. This saliva contains bioactive components which may play a role in pathogen transmission and in host-vector relationships by inducing an immune response in the vertebrate host. The evaluation of human immune responses to arthropod bites might also represent a research direction for assessing individual exposure to the bite of a malaria vector.</p> <p>Methods</p> <p>The present study examined the antibody (Ab) IgG response during the season of exposure to <it>Anopheles gambiae </it>bites in young children living in a malaria endemic area. Immunoblots were performed with <it>An. gambiae </it>saliva to detect anti-saliva Ab bands and the evolution of immunogenic bands at the peak of, and following, the transmission period.</p> <p>Results</p> <p>The results showed that anti-<it>Anopheles </it>Ab was directed against a limited number of salivary proteins (175, 115, 72 and 30 kDa bands). Specific IgG responses to mosquito salivary proteins were variable among exposed individuals; nevertheless, two major bands (175 and 72 kDa) were observed in all immune-responder children. Analysis of the intensity of immunogenic bands revealed that IgG levels against the 175 kDa band were significantly higher during the peak period compared to the end period malaria transmission.</p> <p>Conclusion</p> <p>This preliminary work supports the potential of using anti-saliva immune responses as a measure of exposure to <it>Anopheles </it>bites. The use of immunoblots coupled with evaluation of band intensity could be an adequate tool for distinguishing immunogenic salivary proteins as candidate markers of bite exposure. Furthermore, this study may open the way to design new epidemiological tools for evaluating the risk of malaria exposure.</p

    Evolutionary Advantage Conferred by an Eukaryote-to-Eukaryote Gene Transfer Event in Wine Yeasts

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    Although an increasing number of horizontal gene transfers have been reported in eukaryotes, experimental evidence for their adaptive value is lacking. Here, we report the recent transfer of a 158-kb genomic region between Torulaspora microellipsoides and Saccharomyces cerevisiae wine yeasts or closely related strains. This genomic region has undergone several rearrangements in S. cerevisiae strains, including gene loss and gene conversion between two tandemly duplicated FOT genes encoding oligopeptide transporters. We show that FOT genes confer a strong competitive advantage during grape must fermentation by increasing the number and diversity of oligopeptides that yeast can utilize as a source of nitrogen, thereby improving biomass formation, fermentation efficiency, and cell viability. Thus, the acquisition of FOT genes has favored yeast adaptation to the nitrogen-limited wine fermentation environment. This finding indicates that anthropic environments offer substantial ecological opportunity for evolutionary diversification through gene exchange between distant yeast species

    Stereospecific Lasofoxifene Derivatives Reveal the Interplay between Estrogen Receptor Alpha Stability and Antagonistic Activity in <i>ESR1</i> Mutant Breast Cancer Cells

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    Chemical manipulation of estrogen receptor alpha ligand binding domain structural mobility tunes receptor lifetime and influences breast cancer therapeutic activities. Selective estrogen receptor modulators (SERMs) extend ERα cellular lifetime/accumulation. They are antagonists in the breast but agonists in the uterine epithelium and/or in bone. Selective estrogen receptor degraders/downregulators (SERDs) reduce ERα cellular lifetime/accumulation and are pure antagonists. Activating somatic ESR1 mutations Y537S and D538G enable resistance to first-line endocrine therapies. SERDs have shown significant activities in ESR1 mutant setting while few SERMs have been studied. To understand whether chemical manipulation of ERα cellular lifetime and accumulation influences antagonistic activity, we studied a series of methylpyrollidine lasofoxifene derivatives that maintained the drug’s antagonistic activities while uniquely tuning ERα cellular accumulation. These molecules were examined alongside a panel of antiestrogens in live cell assays of ERα cellular accumulation, lifetime, SUMOylation, and transcriptional antagonism. High-resolution x-ray crystal structures of WT and Y537S ERα ligand binding domain in complex with the methylated lasofoxifene derivatives or representative SERMs and SERDs show that molecules that favor a highly buried helix 12 antagonist conformation achieve the greatest transcriptional suppression activities in breast cancer cells harboring WT/Y537S ESR1. Together these results show that chemical reduction of ERα cellular lifetime is not necessarily the most crucial parameter for transcriptional antagonism in ESR1 mutated breast cancer cells. Importantly, our studies show how small chemical differences within a scaffold series can provide compounds with similar antagonistic activities, but with greatly different effects of the cellular lifetime of the ERα, which is crucial for achieving desired SERM or SERD profiles. SIGNIFICANCE This study shows that antiestrogens that enforce a wild-type-like estrogen receptor alpha antagonist conformation demonstrate improved therapeutic activities in hormone-resistant breast cancer cells harboring activating Y537S ESR1 mutant

    Generation and analysis of a 29,745 unique Expressed Sequence Tags from the Pacific oyster (Crassostrea gigas) assembled into a publicly accessible database: the GigasDatabase

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    Background: Although bivalves are among the most-studied marine organisms because of their ecological role and economic importance, very little information is available on the genome sequences of oyster species. This report documents three large-scale cDNA sequencing projects for the Pacific oyster Crassostrea gigas initiated to provide a large number of expressed sequence tags that were subsequently compiled in a publicly accessible database. This resource allowed for the identification of a large number of transcripts and provides valuable information for ongoing investigations of tissue-specific and stimulus-dependant gene expression patterns. These data are crucial for constructing comprehensive DNA microarrays, identifying single nucleotide polymorphisms and microsatellites in coding regions, and for identifying genes when the entire genome sequence of C. gigas becomes available. Description: In the present paper, we report the production of 40,845 high-quality ESTs that identify 29,745 unique transcribed sequences consisting of 7,940 contigs and 21,805 singletons. All of these new sequences, together with existing public sequence data, have been compiled into a publicly-available Website http://public-contigbrowser.sigenae.org:9090/Crassostrea_gigas/index.htm l. Approximately 43% of the unique ESTs had significant matches against the SwissProt database and 27% were annotated using Gene Ontology terms. In addition, we identified a total of 208 in silico microsatellites from the ESTs, with 173 having sufficient flanking sequence for primer design. We also identified a total of 7,530 putative in silico, single-nucleotide polymorphisms using existing and newly-generated EST resources for the Pacific oyster. Conclusion: A publicly-available database has been populated with 29,745 unique sequences for the Pacific oyster Crassostrea gigas. The database provides many tools to search cleaned and assembled ESTs. The user may input and submit several filters, such as protein or nucleotide hits, to select and download relevant elements. This database constitutes one of the most developed genomic resources accessible among Lophotrochozoans, an orphan clade of bilateral animals. These data will accelerate the development of both genomics and genetics in a commercially-important species with the highest annual, commercial production of any aquatic organism

    Revisiting the genetic diversity of emerging hantaviruses circulating in Europe using a pan-viral resequencing microarray

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    Hantaviruses are zoonotic agents transmitted from small mammals, mainly rodents, to humans, where they provoke diseases such as Hemorrhagic fever with Renal Syndrome (HFRS) and its mild form, Nephropathia Epidemica (NE), or Hantavirus Cardio-Pulmonary Syndrome (HCPS). Hantaviruses are spread worldwide and monitoring animal reservoirs is of primary importance to control the zoonotic risk. Here, we describe the development of a pan-viral resequencing microarray (PathogeniD v3.0) able to explore the genetic diversity of rodent-borne hantaviruses endemic in Europe. Among about 800 sequences tiled on the microarray, 52 correspond to a tight molecular sieve of hantavirus probes covering a large genetic landscape. RNAs from infected animal tissues or from laboratory strains have been reverse transcribed, amplified, then hybridized to the microarray. A classical BLASTN analysis applied to the sequence delivered through the microarray allows to identify the hantavirus species up to the exact geographical variant present in the tested samples. Geographical variants of the most common European hantaviruses from France, Germany, Slovenia and Finland, such as Puumala virus, Dobrava virus and Tula virus, were genetically discriminated. Furthermore, we precisely characterized geographical variants still unknown when the chip was conceived, such as Seoul virus isolates, recently emerged in France and the United Kingdom

    The wave-age-dependent stress parameterisation (WASP) for momentum and heat turbulent fluxes at sea in SURFEX v8.1

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    International audienceA widely applicable parameterisation of turbulent heat and momentum fluxes at sea has been developed for the SURFEX v8.1 surface model. This wave-age-dependent stress parameterisation (WASP) combines a close fit to available in situ observations at sea up to wind speed of 60 m s−1 with the possibility of activating the impact of wave growth on the wind stress. It aims in particular at representing the effect of surface processes that depend on the surface wind according to the state of the art. It can be used with the different atmospheric models coupled with the surface model SURFEX, including the CNRM-CM climate model, the operational (numerical weather prediction) systems in use at MĂ©tĂ©o-France, and the research model Meso-NH. Designed to be used in coupled or forced mode with a wave model, it can also be used in an atmosphere-only configuration. It has been validated and tested in several case studies covering different surface conditions known to be sensitive to the representation of surface turbulent fluxes: (i) the impact of a sea surface temperature (SST) front on low-level flow by weak wind, (ii) the simulation of a Mediterranean heavy precipitating event where waves are known to influence the low-level wind and displace precipitation, (iii) several tropical cyclones, and (iv) a climate run over 35 years. It shows skills comparable to or better than the different parameterisations in use in SURFEX v8.1 so far

    The wave-age dependent stress parameterization (WASP) for momentum and heat turbulent fluxes at sea in SURFEX v8.1

    No full text
    International audienceA widely applicable parameterization of turbulent heat and momentum fluxes at sea has been developed for the SURFEX v8.1 surface model. This wave-age dependent stress parameterization (WASP) combines a close fit to available in situ observations at sea up to wind speed of 60 m s-1 with the possibility of activating the impact of wave growth on the wind stress. It aims in particular at representing the effect of surface processes that depend on the surface wind according to the state of the art. It can be used with the different atmospheric models coupled with the surface model SURFEX, including the CNRM-CM climate model, the operational (numerical weather prediction) systems in use at Météo-France and the research model Meso-NH. Designed to be used in coupled or forced mode with a wave model, it can also be used in atmosphere-only configuration. It has been validated in several case studies covering different surface conditions known to be sensitive to the representation of surface turbulent fluxes: i) the impact of a Sea Surface Temperature (SST) front on low-level flow by weak wind; ii) the simulation of a Mediterranean heavy precipitating event where waves are known to influence the low-level wind and displace precipitation; iii) several tropical cyclones; and iv) a climate run over 35 years. It shows skills comparable to or better than the different parameterizations in use in the SURFEX v8.1 so far

    Fungal, bacterial and plant dsDNA contributions to soil total DNA extracted from silty soils under different farming practices: Relationships with chloroform-labile carbon

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    Twelve differently-managed silty soils from North-Western France were chosen to compare two common methods of quantifying soil microbial biomass: Chloroform fumigation and extraction-labile carbon (CL_C) and microbial double stranded DNA (dsDNA). We also determined the contributions of each of the fungal, bacterial, and plant kingdoms to the total community dsDNA using real-time Polymerase Chain Reaction with kingdom-specific ribosomal primer sets. Regardless of the method, the highest microbial biomasses were associated with long-term untilled plots. Site (locations) specificities could also be detected, especially in conventionally cultivated lands. Regardless of site, a strong linear relationship could be drawn between CL_C and dsDNA in tilled lands (r = 0.91, n = 15, P = 0.01) and in grasslands (r = 0.78, n = 21, P = 0.01). Moreover, we propose a logarithmic model describing all of our silty soils, irrespective of management. In order to explain the non-linearity (log) of this relationship, we tested the hypothesis of a weak plant dsDNA contribution in total dsDNA in comparison with the well-documented root cell contribution to CL_C quantifications. Plant dsDNA never exceeded 2.6% of total dsDNA content for all of the soils studied. Among groups examined, the bacterial dsDNA contribution to the community dsDNA pool was the most site- and/or pedoclimatic-dependent. Fungi constituted a major component of total microbial biomass in grassland or in land with permanent plant cover where their proportion reached almost 50% of total dsDNA. More precisely, fungal dsDNA concentration was highly related to tillage. Our study demonstrated the expediency of the total microbial dsDNA quantification in agricultural silty soils rather than the time-consuming quantification of CL_C. Quantifying the relative contribution of bacterial or fungal biomass in total dsDNA by real-time PCR allows to access to a new level of knowledge of the soil microbial biomass and to reveal the balances between those two kingdoms according to soils or farming practices
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