L’agent simple

En tentant de répondre à la question « pourquoi les écrivains sont-ils de bons critiques ?», Françoise Gaillard montre que leurs textes critiques participent de la même passion, des mêmes choix, du même engagement que leurs textes de fiction. L'écrivain critique n'est pas un agent double, le langage par contre l'est ; voilà pourquoi il est possible de cumuler ces deux activités qui paraissent contradictoires

Comparison of skin microvascular reactivity with hemostatic markers of endothelial dysfunction and damage in type 2 diabetes

AIM: Patients with non-insulin-dependent diabetes mellitus (NIDDM) are at increased cardiovascular risk due to an accelerated atherosclerotic process. The present study aimed to compare skin microvascular function, pulse wave velocity (PWV), and a variety of hemostatic markers of endothelium injury [von Willebrand factor (vWF), plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (t-PA), tissue factor pathway inhibitor (TFPI), and the soluble form of thrombomodulin (s-TM)] in patients with NIDDM. METHODS: 54 patients with NIDDM and 38 sex- and age-matched controls were studied. 27 diabetics had no overt micro- and/or macrovascular complications, while the remainder had either or both. The forearm skin blood flow was assessed by laser-Doppler imaging, which allowed the measurement of the response to iontophoretically applied acetylcholine (endothelium-dependent vasodilation) and sodium nitroprusside (endothelium-independent vasodilation), as well as the reactive hyperemia triggered by the transient occlusion of the circulation. RESULTS: Both endothelial and non-endothelial reactivity were significantly blunted in diabetics, regardless of the presence or the absence of vascular complications. Plasma vWF, TFPI and s-TM levels were significantly increased compared with controls only in patients exhibiting vascular complications. Concentrations of t-PA and PAI-1 were significantly increased in the two groups of diabetics versus controls. CONCLUSION: In NIDDM, both endothelium-dependent and -independent microvascular skin reactivity are impaired, whether or not underlying vascular complications exist. It also appears that microvascular endothelial dysfunction is not necessarily associated in NIDDM with increased circulating levels of hemostatic markers of endothelial damage known to reflect a hypercoagulable state

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