Modulation of microtubule assembly by the HIV-1 Tat protein is strongly dependent on zinc binding to Tat

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Long-term neurological outcome of a cohort of 80 patients with classical organic acidurias.

International audienceBACKGROUND: Classical organic acidurias including methylmalonic aciduria (MMA), propionic aciduria (PA) and isovaleric aciduria (IVA) are severe inborn errors of the catabolism of branched-chain amino acids and odd-numbered chain fatty acids, presenting with severe complications. METHODS: This study investigated the long-term outcome of 80 patients with classical organic aciduria (38 with MMA, 24 with PA and 18 with IVA) by integrating clinical, radiological, biochemical and genetic data. RESULTS: Patients were followed-up for a mean of 14 years [age 3.3-46.3 years]. PA included a greater number of patients with abnormal neurological examination (37% in PA, 24% in MMA and 0% in IVA), lower psychometric scores (abnormal evaluation at age 3 years in 61% of patients with PA versus 26% in MMA and 18% in IVA) and more frequent basal ganglia lesions (56% of patients versus 36% in MMA and 17% in IVA). All patients with IVA presented a normal neurological examination and only 1/3 presented cognitive troubles. Prognosis for MMA was intermediate. Biochemical metabolite analysis excluding acute decompensations revealed significant progressive increases of glycine, alanine and glutamine particularly in PA and possibly in MMA but no correlation with neurological outcome. A significant increase of plasma methylmalonic acid was found in MMA patients with intellectual deficiency (mean level of 199 mumol/L versus 70 mumol/L, p < 0.05), with an estimated significant probability of severe outcome for average levels between birth and age 6 years above 167 mumol/L. Urinary 3-hydroxypropionate (3-HP) levels were significantly higher in PA patients with intellectual deficiency (mean level of 68.9 mumol/mmol of creatinine versus 34.6 mumol/mmol of creatinine, p < 0.01), with an estimated significant probability of severe outcome for average levels between birth and age 6 years above 55 mumol/mmol. As for molecular analysis, prognosis of MMA patients with mutations involving the MMAA gene was better compared to patients with mutations involving the MUT gene. CONCLUSION: Propionic aciduria had the most severe neurological prognosis. Our radiological and biochemical data are consistent with a mitochondrial toxicity mechanism. Follow-up plasma MMA and urinary 3-HP levels may have prognostic significance calling for greater efforts to optimize long-term management in these patients

The ocean sampling day consortium

Ocean Sampling Day was initiated by the EU-funded Micro B3 (Marine Microbial Biodiversity, Bioinformatics, Biotechnology) project to obtain a snapshot of the marine microbial biodiversity and function of the world’s oceans. It is a simultaneous global mega-sequencing campaign aiming to generate the largest standardized microbial data set in a single day. This will be achievable only through the coordinated efforts of an Ocean Sampling Day Consortium, supportive partnerships and networks between sites. This commentary outlines the establishment, function and aims of the Consortium and describes our vision for a sustainable study of marine microbial communities and their embedded functional traits

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

Innovation et développement dans les systèmes agricoles et alimentaires

L’innovation est souvent présentée comme l’un des principaux leviers pour promouvoir un développement plus durable et plus inclusif. Dans les domaines de l’agriculture et de l’alimentation, l’innovation est marquée par des spécificités liées à sa relation à la nature, mais aussi à la grande diversité d’acteurs concernés, depuis les agriculteurs jusqu’aux consommateurs, en passant par les services de recherche et de développement. L’innovation émerge des interactions entre ces acteurs, qui mobilisent des ressources et produisent des connaissances dans des dispositifs collaboratifs, afin de générer des changements. Elle recouvre des domaines aussi variés que les pratiques de production, l’organisation des marchés, ou les pratiques alimentaires. L’innovation est reliée aux grands enjeux de développement : innovation agro-écologique, innovation sociale, innovation territoriale, etc. Cet ouvrage porte un regard sur l’innovation dans les systèmes agricoles et alimentaires. Il met un accent particulier sur l’accompagnement de l’innovation, en interrogeant les méthodes et les organisations, et sur l’évaluation de l’innovation au regard de différents critères. Il s’appuie sur des réflexions portées par différentes disciplines scientifiques, sur des travaux de terrain conduits tant en France que dans de nombreux pays du Sud, et enfin sur les expériences acquises en accompagnant des acteurs qui innovent. Il combine des synthèses sur l’innovation et des études de cas emblématiques pour illustrer les propos. L’ouvrage est destiné aux enseignants, professionnels, étudiants et chercheurs

Résultats de théorie abstraite des modèles dans le cadre des institutions : vers la combinaison de logiques

De nombreux travaux ont montré l'importance de l'interpolation de Craig pour la structuration et la modularité des spécifications de type axiomatique. En vue d'en donner des conditions suffisantes dans un cadre théorique adapté à l'informatique, nous nous sommes intéressé à une propriété équivalente à l'interpolation de Craig dans le cadre de la théorie standard des modèles : la consistance de Robinson. L'étude de cette dernière propriété nous a amené à généraliser dans une spécialisation des institutions les notions classiques de diagrammes complets et de morphismes élémentaires. Ceci nous a alors permis de généraliser quelques résultats classiques de théorie des modèles tels que les théorèmes de Löwenheim-Skolem ou l'union de chaînes de Tarski. En fin, les constructeurs de formules étant explicites dans notre cadre théorique, nous nous sommes naturellemant intéressés à la combinaison de logiques et à la préservation de l'interpolation de Craig et de la consistance de Robinson.The importance of Craig interpolation for structuration and modularity of axiomatic style specifications have been shown by many works. In order to give sufficient conditions to Craig interpolation in a suitable framework for computer science, we've studied a propery equivalent to Craig interpolation in standard model theory: Robinson consistency. To do so, we had to generalize the notions of complete diagrams and elementary morphisms in a specialization of institutions. This allowed the generalization of other classical standard model theory results such as Löwenheim-Skolem theorem and Tarski chain union. Finally, since formulae constructors are explicite in our framework, we've studied logic combination and the preservation of both Craig interpolation and Robinson consistency through combination.EVRY-BU (912282101) / SudocSudocFranceF

Theoretical studies of the ground state and of the spectroscopic properties of ethyl 5-amino-2-methyl-1,2-dihydro-3-phenylpyrido[3,4-b]pyrazin-7-yl carbamate analogs

International audienceThe interaction of antimitotic compounds with tubulin has been studied in detail in our laboratory; among them, the two chiral isomers of ethyl 5-amino-2-methyl-1,2-dihydro-3-phenylpyrido[3,4-b]pyrazin-7-yl carbamate, NSC 613863 (R)-(1) and NSC 613862 (S)-(2) (CI980) and the three achiral analogs NSC 330770 (ethyl 5-amino-1,2-dihydro-3-phenylpyrido[3,4-b]pyrazin-7-yl carbamate), NSC 337238 (ethyl 5-amino-3-phenylpyrido[3,4-b]pyrazin-7-yl carbamate) and C179 (ethyl 5-amino-2-methyl-3-phenylpyrido[3,4-b]pyrazin-7-yl carbamate). In this study, by AM1 calculations, we have investigated the ground state (S 0), the near-UV absorption, the fluorescence emission properties of these compounds in the order to better understand the behavior of each drug and to enlighten their binding mechanism to tubulin. A modification of the ring B such as a methyl substituent or a second insaturation center drastically modified the affinity for tubulin. AM1 results indicated that ring A and B were mainly involved in the first step of binding to tubulin, the second step consisted in the interaction of the phenyl ring C. The spectra of the compounds have shown that an excited state rearrangement took place and that the molecules in the S1 state are rendered more planar. The rotation of the phenyl appeared to be an unfavorable pathway but an imino form, stabilized by an intramolecular hydrogen bond between the COO moiety of the side chain and an hydrogen at atom N6 could play a role either in the S0 and/or in the S1 state