31 research outputs found

    Protéger la nation ?

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    Au lendemain du 13 novembre 2015, après avoir « beaucoup réfléchi à cette question », le Président Hollande, devant le Congrès réuni à Versailles, estimait « en conscience que nous devons faire évoluer notre Constitution pour permettre aux pouvoirs publics d’agir, conformément à l’état de droit, contre le terrorisme de guerre ». Toujours selon le Président, « ces attentats poursuivent un objectif bien précis : semer la peur pour nous diviser ici ». Avis pris auprès du Conseil d’État, un proje..

    Finding a Needle in the Virus Metagenome Haystack - Micro-Metagenome Analysis Captures a Snapshot of the Diversity of a Bacteriophage Armoire

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    Viruses are ubiquitous in the oceans and critical components of marine microbial communities, regulating nutrient transfer to higher trophic levels or to the dissolved organic pool through lysis of host cells. Hydrothermal vent systems are oases of biological activity in the deep oceans, for which knowledge of biodiversity and its impact on global ocean biogeochemical cycling is still in its infancy. In order to gain biological insight into viral communities present in hydrothermal vent systems, we developed a method based on deep-sequencing of pulsed field gel electrophoretic bands representing key viral fractions present in seawater within and surrounding a hydrothermal plume derived from Loki's Castle vent field at the Arctic Mid-Ocean Ridge. The reduction in virus community complexity afforded by this novel approach enabled the near-complete reconstruction of a lambda-like phage genome from the virus fraction of the plume. Phylogenetic examination of distinct gene regions in this lambdoid phage genome unveiled diversity at loci encoding superinfection exclusion- and integrase-like proteins. This suggests the importance of fine-tuning lyosgenic conversion as a viral survival strategy, and provides insights into the nature of host-virus and virus-virus interactions, within hydrothermal plumes. By reducing the complexity of the viral community through targeted sequencing of prominent dsDNA viral fractions, this method has selectively mimicked virus dominance approaching that hitherto achieved only through culturing, thus enabling bioinformatic analysis to locate a lambdoid viral “needle" within the greater viral community “haystack". Such targeted analyses have great potential for accelerating the extraction of biological knowledge from diverse and poorly understood environmental viral communities

    Démocratie et constitutionnalisme. Retours critiques

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    Petit à petit, l’illibéralisme fait son nid : quand la loi immigration annonce d’autres atteintes à l’Etat de droit.

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    International audienceComme à chaque décision de Cours suprêmes un tant soit peu sensible, la décision rendue par le Conseil constitutionnel sur la loi dite « Darmanin » a été l’occasion pour certain-es figures conservatrices et critiques de « l’Etat de droit » de reprendre la plume pour s’inquiéter de ce que le Parlement « ne pourrait plus légiférer » dès lors qu’il est question d’immigration ou de sécurité. Vieille antienne : le droit et le gouvernement des juges auraient vaincu en ce domaine la politique et la volonté des représentants du peuple

    Are abatacept and tocilizumab intravenous users willing to switch for the subcutaneous route of administration? A questionnaire-based study

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    International audienceChoosing the subcutaneous (SC) route of administration of abatacept and tocilizumab is more cost-effective than the intravenous (IV) route. The objective of this study was to examine patients' reasons for choosing to keep with their IV infusions or to switch to subcutaneous SC injections. This study was based upon a self-administered questionnaire given to consecutive rheumatoid arthritis patients treated with abatacept or tocilizumab. Patients were asked to express their opinions concerning reasons explaining why they chose to keep the IV route or switch to the SC route. A total of 201 questionnaires completed by 127 patients treated by tocilizumab and 74 by abatacept were analysed. Overall, 45.8% of the patients chose to keep the IV route of administration. Another ongoing SC treatment was noted more often in patients choosing the SC route (15.9 versus 4.3%, p < 0.05). Reasons guiding the choice of the SC route were concerns about repeated hospital day-care (72%), greater autonomy with SC injections (38.7%) and economic considerations (21.5%). Reasons associated with choosing to maintain the IV route were worries about a lack of follow-up (72.1%), the absence of medical assistance during the SC injection (61.2%), maintaining social relationships with other patients developed at the hospital (40.5%), lower frequency of injection (32.9%), fear of adverse events (27.7%) and fear of SC injections (17.9%). Patients reject the SC switch from the IV route of tocilizumab and abatacept mainly because of fears about the unknown SC route, while those who accept it find it more convenient

    Être Charlie

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    International audienceAu lendemain des massacres perpétrés les 7, 8 et 9 janvier dans les locaux de Charlie Hebdo, à Montrouge et à l'Hyper Cacher, on s'en souvient, le slogan de soutien et de solidarité "Je suis Charlie" s'est diffusé à l'ensemble de la planète. Cinq mois plus tard, comment faire perdurer le mélange de solidarité et de vigilance qu'il entendait porter

    A Bacteriophage-Encoded J-Domain Protein Interacts with the DnaK/Hsp70 Chaperone and Stabilizes the Heat-Shock Factor σ<sup>32</sup> of <em>Escherichia coli</em>

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    <div><p>The universally conserved J-domain proteins (JDPs) are obligate cochaperone partners of the Hsp70 (DnaK) chaperone. They stimulate Hsp70's ATPase activity, facilitate substrate delivery, and confer specific cellular localization to Hsp70. In this work, we have identified and characterized the first functional JDP protein encoded by a bacteriophage. Specifically, we show that the ORFan gene <em>057w</em> of the T4-related enterobacteriophage RB43 encodes a <em>bona fide</em> JDP protein, named Rki, which specifically interacts with the <em>Escherichia coli</em> host multifunctional DnaK chaperone. However, in sharp contrast with the three known host JDP cochaperones of DnaK encoded by <em>E. coli</em>, Rki does not act as a generic cochaperone <em>in vivo</em> or <em>in vitro</em>. Expression of Rki alone is highly toxic for wild-type <em>E. coli</em>, but toxicity is abolished in the absence of endogenous DnaK or when the conserved J-domain of Rki is mutated. Further <em>in vivo</em> analyses revealed that Rki is expressed early after infection by RB43 and that deletion of the <em>rki</em> gene significantly impairs RB43 proliferation. Furthermore, we show that mutations in the host <em>dnaK</em> gene efficiently suppress the growth phenotype of the RB43 <em>rki</em> deletion mutant, thus indicating that Rki specifically interferes with DnaK cellular function. Finally, we show that the interaction of Rki with the host DnaK chaperone rapidly results in the stabilization of the heat-shock factor σ<sup>32</sup>, which is normally targeted for degradation by DnaK. The mechanism by which the Rki-dependent stabilization of σ<sup>32</sup> facilitates RB43 bacteriophage proliferation is discussed.</p> </div

    Analysis of the various J-domain chimera phenotypes <i>in vivo</i>.

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    <p>(A) The RB43 genome region containing the ORF057w, adapted from <a href="http://bacteriophage.bioc.tulane.edu/" target="_blank">http://bacteriophage.bioc.tulane.edu/</a>. Genes in black have orthologs in bacteriophage T4. (B) An alignment of the J-domain primary amino acid sequences using ClustalX. Identical residues are shown in black and conserved substitutions in gray. The limits of α-helical secondary structures in the DnaJ J-domain are also shown (black bars). (C) Complementation of the temperature-sensitive phenotype of the bacterial strain W3110 Δ3 (<i>dnaJ cbpA djlA</i> triple mutant) by the various pBAD22-based J-domain chimeras in the presence of 0.01% L-arabinose inducer. Only the origin of the relevant J-domain is shown on top of the figure, the rest of the protein being always that of <i>E. coli</i>'s DnaJ. (D) Complementation assay for bacteriophage λ<i>c</i>I(λ) plaque formation on strain Δ3 using the pBAD22-based J-domain chimeras in the presence of 0.001% L-arabinose at 30°C. The λ<i>c</i>I<i>dnaJ+</i> transducing bacteriophage (λJ+) is shown as a positive control. (E) Complementation for bacterial motility assay showing the radial growth of strain Δ3 expressing the pBAD22-based J-domain chimeras in the presence of 0.001% L-arabinose. (F) The relative steady state level of the various DnaJ chimera constructs expressed in strain W3110 Δ3 at 30°C in the presence of 0.1% L-arabinose, following SDS–PAGE of the extracts and staining with Coomassie blue.</p

    Rki cochaperone functions <i>in vitro</i>.

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    <p>(A) Stimulation of DnaK ATPase activity under steady state conditions. DnaK(1 µM) and GrpE (0.5 µM) in the absence or in the presence of DnaJ, Rki or Rki(H38Q) at the indicated concentrations. The percentage hydrolyzed ATP/min is plotted as a function of the final DnaJ concentration used in the reaction mix. (B) Refolding chemically-denatured firefly luciferase (125 nM) by DnaK (500 nM) and GrpE (125 nM) in the presence of 125 nM of either DnaJ, Rki or Rki(H38Q) as indicated. The values of luciferase refolding were normalized to the maximal value obtained with that of wild type DnaJ. (C) Luciferase aggregation protection assay. A representative plot of a luciferase aggregation protection assay is shown with chemically-denatured luciferase (1 µM) alone (no JDP), or in the presence of DnaJ (1 µM), Rki (1 µM or 4 µM). Optical densities were measured at 320 nm and the percentage values were normalized to the luciferase aggregation obtained in the absence of added chaperones.</p
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