79 research outputs found

    De la sacralité du pouvoir : des mémorialistes et leurs représentations de la mort des dirigeants politiques français du XVIIe siècle

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    Québec Université Laval, Bibliothèque 201

    A small protein coded within the mitochondrial canonical gene nd4 regulates mitochondrial bioenergetics

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    BACKGROUND: Mitochondria have a central role in cellular functions, aging, and in certain diseases. They possess their own genome, a vestige of their bacterial ancestor. Over the course of evolution, most of the genes of the ancestor have been lost or transferred to the nucleus. In humans, the mtDNA is a very small circular molecule with a functional repertoire limited to only 37 genes. Its extremely compact nature with genes arranged one after the other and separated by short non-coding regions suggests that there is little room for evolutionary novelties. This is radically different from bacterial genomes, which are also circular but much larger, and in which we can find genes inside other genes. These sequences, different from the reference coding sequences, are called alternatives open reading frames or altORFs, and they are involved in key biological functions. However, whether altORFs exist in mitochondrial protein-coding genes or elsewhere in the human mitogenome has not been fully addressed. RESULTS: We found a downstream alternative ATG initiation codon in the + 3 reading frame of the human mitochondrial nd4 gene. This newly characterized altORF encodes a 99-amino-acid-long polypeptide, MTALTND4, which is conserved in primates. Our custom antibody, but not the pre-immune serum, was able to immunoprecipitate MTALTND4 from HeLa cell lysates, confirming the existence of an endogenous MTALTND4 peptide. The protein is localized in mitochondria and cytoplasm and is also found in the plasma, and it impacts cell and mitochondrial physiology. CONCLUSIONS: Many human mitochondrial translated ORFs might have so far gone unnoticed. By ignoring mtaltORFs, we have underestimated the coding potential of the mitogenome. Alternative mitochondrial peptides such as MTALTND4 may offer a new framework for the investigation of mitochondrial functions and diseases

    Essential Gene Identification and Drug Target Prioritization in Aspergillus fumigatus

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    Aspergillus fumigatus is the most prevalent airborne filamentous fungal pathogen in humans, causing severe and often fatal invasive infections in immunocompromised patients. Currently available antifungal drugs to treat invasive aspergillosis have limited modes of action, and few are safe and effective. To identify and prioritize antifungal drug targets, we have developed a conditional promoter replacement (CPR) strategy using the nitrogen-regulated A. fumigatus NiiA promoter (pNiiA). The gene essentiality for 35 A. fumigatus genes was directly demonstrated by this pNiiA-CPR strategy from a set of 54 genes representing broad biological functions whose orthologs are confirmed to be essential for growth in Candida albicans and Saccharomyces cerevisiae. Extending this approach, we show that the ERG11 gene family (ERG11A and ERG11B) is essential in A. fumigatus despite neither member being essential individually. In addition, we demonstrate the pNiiA-CPR strategy is suitable for in vivo phenotypic analyses, as a number of conditional mutants, including an ERG11 double mutant (erg11BΔ, pNiiA-ERG11A), failed to establish a terminal infection in an immunocompromised mouse model of systemic aspergillosis. Collectively, the pNiiA-CPR strategy enables a rapid and reliable means to directly identify, phenotypically characterize, and facilitate target-based whole cell assays to screen A. fumigatus essential genes for cognate antifungal inhibitors

    Saccharomyces cerevisiae chitin biosynthesis activation by N-acetylchitooses depends on size and structure of chito-oligosaccharides

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    <p>Abstract</p> <p>Background</p> <p>To explore chitin synthesis initiation, the effect of addition of exogenous oligosaccharides on <it>in vitro </it>chitin synthesis was studied. Oligosaccharides of various natures and lengths were added to a chitin synthase assay performed on a <it>Saccharomyces cerevisiae </it>membrane fraction.</p> <p>Findings</p> <p><it>N</it>-acetylchito-tetra, -penta and -octaoses resulted in 11 to 25% [<sup>14</sup>C]-GlcNAc incorporation into [<sup>14</sup>C]-chitin, corresponding to an increase in the initial velocity. The activation appeared specific to <it>N</it>-acetylchitooses as it was not observed with oligosaccharides in other series, such as beta-(1,4), beta-(1,3) or alpha-(1,6) glucooligosaccharides.</p> <p>Conclusions</p> <p>The effect induced by the <it>N</it>-acetylchitooses was a saturable phenomenon and did not interfere with free GlcNAc and trypsin which are two known activators of yeast chitin synthase activity <it>in vitro</it>. The magnitude of the activation was dependent on both oligosaccharide concentration and oligosaccharide size.</p

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    Sous la direction de Giovanni CareriAvec la participation de Sylviane Agacinski, Jacques Aumont, Jean-Claude Bonne, Stéphane Breton, Annie Cohen-Solai, Danièle Cohn, Jean-Paul Colleyn, Michel de Fornel, Brigitte Derlon, Georges Didi-Huberman, Pierre Encrevé, Patricia Falguières, André Gunthert, Yves Hersant, François Lissarrague, Éric Michaud, Jean-Claude Penrad, Jean-Claude Schmitt, Carlo Severi et Éliane de Latour Le programme de cette année a été essentiellement consacré à l’approche anthr..

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    Sous la direction de Giovanni CareriAvec la participation de Sylviane Agacinski, Jacques Aumont, Jean-Claude Bonne, Stéphane Breton, Annie Cohen-Solai, Danièle Cohn, Jean-Paul Colleyn, Michel de Fornel, Brigitte Derlon, Georges Didi-Huberman, Pierre Encrevé, Patricia Falguières, André Gunthert, Yves Hersant, François Lissarrague, Éric Michaud, Jean-Claude Penrad, Jean-Claude Schmitt, Carlo Severi et Éliane de Latour Le programme de cette année a été essentiellement consacré à l’approche anthr..

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    Participants : Sylviane Agacinski, Daniel Arasse, Jacques Aumont, Jean-Claude Bonne, Stéphane Breton, Giovanni Careri, Annie Cohen-Solal, Danièle Cohn, Jean-Paul Colleyn, Michel de Fornel, Brigitte Derlon, Georges Didi-Huberman, Pierre Encrevé, Patricia Falguières, André Gunthert, Yves Hersant, Éliane de Latour, François Lissarrague, Éric Michaud, Jean-Claude Penrad, Jean-Claude Schmitt, Carlo Severi La fabrique des images. Politiques de l’image Le séminaire de la filière « Images » a été cet..

    Filière « Images »

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    Participants : Sylviane Agacinski, Daniel Arasse, Jacques Aumont, Jean-Claude Bonne, Stéphane Breton, Giovanni Careri, Annie Cohen-Solal, Danièle Cohn, Jean-Paul Colleyn, Michel de Fornel, Brigitte Derlon, Georges Didi-Huberman, Pierre Encrevé, Patricia Falguières, André Gunthert, Yves Hersant, Éliane de Latour, François Lissarrague, Éric Michaud, Jean-Claude Penrad, Jean-Claude Schmitt, Carlo Severi La fabrique des images. Politiques de l’image Le séminaire de la filière « Images » a été cet..

    Landscape in motion. Recommissioning Andøya Air Station

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    Technological Blindness and Blindness Liberal : Singularities, Analogies and Interactions within Organizations

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    L’enjeu de cette thèse était d’explorer et d’analyser au niveau organisationnel :- que certaines technologies - aussi séduisantes et utiles soient-elles - s’immiscent dans nos vies (immixtion et/ou immersion volontaire) ou nous sont imposées sans débat ni critique par les acteurs du marché tout en produisant de nouvelles formes de vie : c’est l’aveuglement technologique ; - alors que le système politique devrait réguler par le contrôle, c’est le libéralisme qui prévaut par les nouvelles formes ou lieux de pouvoirs, la mondialisation, et la financiarisation de l’économie manifestant un autre aveuglement : l’aveuglement libéral. Ces deux aveuglements ont-ils des analogies, des singularités, des liens et des interactions au sein des organisations ? Si tel est le cas, cela conduirait, peut-être, à une résultante très peu explicitée et donc peu étudiée : un aveuglement organisationnel ? Notre travail doctoral apporte une réponse positive à ces deux questions.This thesis was explores and analyses at organisational level:- the fact that certain technologies – however seductive and useful they are – intrude in our lives (intrusion and/or voluntary immersion) or are imposed on us without debate or criticism by market players and produce new forms of life : this is technological blindness; - the fact that while the political system should regulate and control, market forces dominate through new forms or centres of power ; globalisation and the financialised economy are manifestations of another type of blindness : liberalist blindness. Do these two types of blindness have analogies, particular features, links and interactions within organisations? If so, might this generate a phenomenon that has hardly been identified or studied : organisational blindness? My doctoral work answers these two questions in the affirmative
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