Supramolecular agent–simulant correlations for the luminescence based detection of V-series chemical warfare agents with trivalent lanthanide complexes

Solution spectroscopic investigations into the interactions of eight potential bidentate V-series organophosphorus chemical warfare agent (OP CWA) simulants with [Eu(phen)₂(NO₃)₃]·2H₂O demonstrated that the chemical and structural composition of the secondary binding site within the simulant was of paramount importance. Only simulants containing both phosphoryl/phosphonyl and amine moieties generated analogous spectroscopic behaviours to V-series OP CWAs seen in previous studies. The results demonstrated that the bidentate chelation mechanism was driven by the phosphoryl/phosphonyl moieties and that the presence of the amine moieties induced a significant secondary dynamic luminescence quenching mechanism. The binding modes of the simulants VO and TEEP to trivalent lanthanides (Eu and La) were further investigated using ¹H and ³¹P NMR spectroscopic titrations and kinetic IR experiments. VO, with both the phosphonyl and amine binding sites was found to be the most appropriate simulant for V-series OP CWAs in supramolecular studies with trivalent lanthanide ions and we recommend VO for use in supramolecular studies of this type

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Réussir le CAPES externe d'anglais

CD-MP3 inclusNational audienceCet ouvrage se propose de donner aux candidats au Capes externe d'anglais une préparation complète, en un seul volume, à l'ensemble des épreuves d'admissibilité et d'admission du concours (traduction/linguistique, commentaire dirigé de littérature, commentaire dirigé de civilisation, épreuve sur dossier et leçon) et au métier d'enseignant de langue vivante

Quand l'art lit/lie l'oeuvre (ateliers dans un colloque)

International audienceAteliers sur la création littéraire et les rencontres avec des auteurs et des créateurs en class

Arsenic Biogeochemistry Affected by Eutrophication in Lake Biwa, Japan (INTERFACE SCIENCE-Separation Chemistry)

The seasonal variations of arsenic species were studied in the mesotrophic northern and eutrophic southern basins of Lake Biwa in Japan. The variations of arsenic species in lake water largely depend on biological processes, such as the metabolism of phytoplankton, decomposition of organic matter by bacteria, and microbial reduction of iron and manganese oxides in sediments. These results show that eutrophication affects the concentration and speciation of arsenic in the lake water

Sing und Spiel mit Uns CE1, Méthode de langue

International audienceMéthode d'enseignement de l'allemand en primaire (classe de CE1

Sing und Spiel Mit Uns CP, Méthode de langue

International audienceMéthode de langue pour l'enseignement de l'allemand au primaire (classe de CP

Draft Genome Sequence of the Principal Etiological Agent of Farmer's Lung Disease, Saccharopolyspora rectivirgula.

International audienceSaccharopolyspora rectivirgula is the main cause of farmer's lung disease. The development of recombinant antigens to standardize the serodiagnosis of the disease requires knowledge of the S. rectivirgula genome. We sequenced the genome of an environmental strain, S. rectivirgula DSM 43113. A total of 3,221 proteins were found to be encoded in a short 3.9-Mb genome

Proposition d’une marche à suivre pour la gestion et la prévention d’extravasation d’agents non cytotoxiques

Résumé Objectifs : Revoir la documentation scientifique et proposer une marche à suivre lors d’extravasation d’agents non cytotoxiques. Problématique : La documentation scientifique concernant l’extravasation d’agents non cytotoxiques est limitée. Un groupe de travail multidisciplinaire au sein des Hôpitaux universitaires genevois a été créé afin de déterminer les différents facteurs de risques d’extravasation et d’élaborer une démarche de prise en charge lors d’extravasation d’agents non cytotoxiques. Discussion : Afin d’éviter de lourdes conséquences pour le patient, le pharmacien se doit de connaître la marche à suivre ainsi que les mesures spécifiques à appliquer lors d’extravasation de certaines substances. La gestion et le suivi des extravasations passent par une bonne connaissance des mécanismes des dommages tissulaires provoqués par une molécule ainsi que des différents facteurs de risques associés. La nature de la molécule injectée (irritante ou vésicante), l’administration (la voie, le volume, la durée et le site), le type de patient ainsi que le personnel soignant sont tous des éléments pouvant influencer la probabilité d’avoir une extravasation symptomatique. Conclusion : Cette procédure a permis de standardiser la prise en charge des patients lors d’extravasation avec des agents non cytotoxiques. Les professionnels de la santé dans ce milieu hospitalier ont accès à ces informations sur le site internet de l’établissement. Abstract Objectives: To review the scientific literature and to suggest steps to follow during the extravasation of non-cytotoxic agents. Problem: The scientific literature for the extravasation of non-cytotoxic agents is limited. A multidisciplinary workgroup at the Geneva university hospitals was created to determine the different risk factors for extravasation and to develop a procedure to follow during the extravasation of non-cytotoxic agents. Discussion: To avoid harmful consequences to the patient, the pharmacist should know the steps to follow in addition to the specific measures to apply during the extravasation of certain substances. Proper knowledge of the mechanism of tissue damage induced by each substance and knowledge of associated risk factors are needed for the management and follow-up of extravasations. The nature of the injected substance (whether an irritant or vesicant), administration issues (route, volume, duration, site), the type of patient as well as healthcare providers— these are all factors that can influence the probability of symptomatic extravasation. Conclusion: This procedure standardized the management of patients during extravasation with noncytotoxic agents. Healthcare professionals in this hospital have access to this information on the hospital’s website. Key words: extravasation, non-cytotoxic medications, managemen