Genomics of glycopeptidolipid biosynthesis in Mycobacterium abscessus and M. chelonae

<p>Abstract</p> <p>Background</p> <p>The outermost layer of the bacterial surface is of crucial importance because it is in constant interaction with the host. Glycopeptidolipids (GPLs) are major surface glycolipids present on various mycobacterial species. In the fast-grower model organism <it>Mycobacterium smegmatis</it>, GPL biosynthesis involves approximately 30 genes all mapping to a single region of 65 kb.</p> <p>Results</p> <p>We have recently sequenced the complete genomes of two fast-growers causing human infections, <it>Mycobacterium abscessus </it>(CIP 104536T) and <it>M. chelonae </it>(CIP 104535T). We show here that these two species contain genes corresponding to all those of the <it>M. smegmatis </it>"GPL locus", with extensive conservation of the predicted protein sequences consistent with the production of GPL molecules indistinguishable by biochemical analysis. However, the GPL locus appears to be split into several parts in <it>M. chelonae </it>and <it>M. abscessus</it>. One large cluster (19 genes) comprises all genes involved in the synthesis of the tripeptide-aminoalcohol moiety, the glycosylation of the lipopeptide and methylation/acetylation modifications. We provide evidence that a duplicated acetyltransferase (<it>atf1 </it>and <it>atf2</it>) in <it>M. abscessus </it>and <it>M. chelonae </it>has evolved through specialization, being able to transfer one acetyl at once in a sequential manner. There is a second smaller and distant (<it>M. chelonae</it>, 900 kb; <it>M. abscessus</it>, 3 Mb) cluster of six genes involved in the synthesis of the fatty acyl moiety and its attachment to the tripeptide-aminoalcohol moiety. The other genes are scattered throughout the genome, including two genes encoding putative regulatory proteins.</p> <p>Conclusion</p> <p>Although these three species produce identical GPL molecules, the organization of GPL genes differ between them, thus constituting species-specific signatures. An hypothesis is that the compact organization of the GPL locus in <it>M. smegmatis </it>represents the ancestral form and that evolution has scattered various pieces throughout the genome in <it>M. abscessus </it>and <it>M. chelonae</it>.</p

APRIL is overexpressed in cancer: link with tumor progression

<p>Abstract</p> <p>Background</p> <p>BAFF and APRIL share two receptors – TACI and BCMA – and BAFF binds to a third receptor, BAFF-R. Increased expression of BAFF and APRIL is noted in hematological malignancies. BAFF and APRIL are essential for the survival of normal and malignant B lymphocytes, and altered expression of BAFF or APRIL or of their receptors (BCMA, TACI, or BAFF-R) have been reported in various B-cell malignancies including B-cell non-Hodgkin's lymphoma, chronic lymphocytic leukemia, Hodgkin's lymphoma, multiple myeloma, and Waldenstrom's macroglobulinemia.</p> <p>Methods</p> <p>We compared the expression of <it>BAFF, APRIL, TACI and BAFF-R </it>gene expression in 40 human tumor types – brain, epithelial, lymphoid, germ cells – to that of their normal tissue counterparts using publicly available gene expression data, including the Oncomine Cancer Microarray database.</p> <p>Results</p> <p>We found significant overexpression of <it>TACI </it>in multiple myeloma and thyroid carcinoma and an association between TACI expression and prognosis in lymphoma. Furthermore, <it>BAFF and APRIL </it>are overexpressed in many cancers and we show that <it>APRIL </it>expression is associated with tumor progression. We also found overexpression of at least one proteoglycan with heparan sulfate chains (HS), which are coreceptors for APRIL and TACI, in tumors where APRIL is either overexpressed or is a prognostic factor. APRIL could induce survival or proliferation directly through HS proteoglycans.</p> <p>Conclusion</p> <p>Taken together, these data suggest that APRIL is a potential prognostic factor for a large array of malignancies.</p

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Une double mise à distance sociale et spatiale des sidérurgistes et de leurs enfants dans le Longwy des années 1980

International audienceNumerous studies on the industrial restructurings assert that we attend the emergence of a new territorial question which would substitute itself to the social question of the workers and their fights. The area of Longwy in the 1980s is a “privileged” ground of observation to think about it. The numerous decisions of steel-making factory closures, the intense fights which they caused, the multiplicity of conversion plans for activities, workers and territory that followed, are translated by a social and spatial removal of steel-makers and their children. The mobilized researches show that it reveals the conflicting transformations of the wage-earner, from the collective rights of internal markets towards the individualization of the rights which accompany their weakening.De nombreuses études sur les restructurations industrielles affirment qu’on assiste à l’émergence d’une nouvelle question territoriale qui se substituerait à la question sociale hier essentiellement constituée des ouvriers et de leurs combats. Le bassin de Longwy des années 1980 est un terrain d’observation « privilégié » pour y réfléchir. Les nombreuses décisions de fermetures d’usines sidérurgiques, les luttes intenses qu’elles ont provoquées, la multiplicité des dispositifs de conversion des activités, des hommes et du territoire qui ont suivi, se traduisent par une double mise à distance sociale et spatiale des sidérurgistes et de leurs enfants. Les recherches mobilisées montrent qu’elle révèle avant tout les transformations conflictuelles du salariat, des droits collectifs liés aux marchés internes vers l’individualisation des droits qui accompagne leur affaiblissement

Je travaille au Luxembourg : Une socio-histoire d’un espace de qualification transfrontalier

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Collectif du 9 août, Quand ils ont fermé l’usine. Lutter contre la délocalisation dans une économie globalisée

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Les fermetures d’usines dans un espace social localisé de qualification :

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QUESTION SOCIALE ET QUESTION TERRITORIALE: Le bassin de Longwy de la première moitié des années 1980

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« Longwy vous accueille, JVC nous jette »

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