Evolutionary comparisons reveal a positional switch for spindle pole oscillations in Caenorhabditis embryos.

International audienceDuring the first embryonic division in Caenorhabditis elegans, the mitotic spindle is pulled toward the posterior pole of the cell and undergoes vigorous transverse oscillations. We identified variations in spindle trajectories by analyzing the outwardly similar one-cell stage embryo of its close relative Caenorhabditis briggsae. Compared with C. elegans, C. briggsae embryos exhibit an anterior shifting of nuclei in prophase and reduced anaphase spindle oscillations. By combining physical perturbations and mutant analysis in both species, we show that differences can be explained by interspecies changes in the regulation of the cortical Gα-GPR-LIN-5 complex. However, we found that in both species (1) a conserved positional switch controls the onset of spindle oscillations, (2) GPR posterior localization may set this positional switch, and (3) the maximum amplitude of spindle oscillations is determined by the time spent in the oscillating phase. By investigating microevolution of a subcellular process, we identify new mechanisms that are instrumental to decipher spindle positioning

Relationship between haemagglutination-inhibiting antibody titres and clinical protection against influenza: development and application of a bayesian random-effects model

<p>Abstract</p> <p>Background</p> <p>Antibodies directed against haemagglutinin, measured by the haemagglutination inhibition (HI) assay are essential to protective immunity against influenza infection. An HI titre of 1:40 is generally accepted to correspond to a 50% reduction in the risk of contracting influenza in a susceptible population, but limited attempts have been made to further quantify the association between HI titre and protective efficacy.</p> <p>Methods</p> <p>We present a model, using a meta-analytical approach, that estimates the level of clinical protection against influenza at any HI titre level. Source data were derived from a systematic literature review that identified 15 studies, representing a total of 5899 adult subjects and 1304 influenza cases with interval-censored information on HI titre. The parameters of the relationship between HI titre and clinical protection were estimated using Bayesian inference with a consideration of random effects and censorship in the available information.</p> <p>Results</p> <p>A significant and positive relationship between HI titre and clinical protection against influenza was observed in all tested models. This relationship was found to be similar irrespective of the type of viral strain (A or B) and the vaccination status of the individuals.</p> <p>Conclusion</p> <p>Although limitations in the data used should not be overlooked, the relationship derived in this analysis provides a means to predict the efficacy of inactivated influenza vaccines when only immunogenicity data are available. This relationship can also be useful for comparing the efficacy of different influenza vaccines based on their immunological profile.</p

Contribution au développement de marqueurs technétiés pour l'exploration des transporteurs des monoamines dans le système nerveux central

Notre travail porte sur la synthèse de radiopharmaceutiques permettant l'exploration scintigraphique des transporteurs des monoamines par tomographie d'émission monophotonique (SPET). Des modifications de la densité et de la fonction de ces transporteurs sont observées lors de maladies neurodégénératives et psychiatriques (Parkinson, dépression, schizophrénie). Le but est d'établir un diagnostic précoce et d'évaluer l'efficacité des traitements mis en place lors de ces maladies. Pour réaliser ces études, il est nécessaire de développer des radiopharmaceutiques, émetteurs de rayonnement y, spe cifiques de ces transporteurs. Dans le cadre d'un projet européen EUREKA (Projet EU 1836), notre étude à conduit à l'élaboration de trois nouveaux traceurs technétiés dérivés du tropane portant un système complexant de type oxocyclam. Les marquages au 99mTc ont été réalisés. Les premiers tests biologiques effectués sur ces composés ont révélé une faible fixation au transporteur de la dopamine et un passage difficile de la barrière hématoencéphalique. Des modifications structurales de ces composés doivent donc être apportées pour améliorer leurs propriétés biologiques. Lors de ces travaux, une collaboration s'est établie avec un laboratoire de l'Université de Yale pour étudier un mécanisme de réarrangement du cycle tropane observé lors de la synthèse d'un intermédiaire précurseur: le 2b-méthanesulfonyloxyméthyl3b-p-tolyltropane. Enfin, nous avons débuté l'étude d'une synthèse d'un nouveau type de dérivés du tropane dans l'objectif d'aborder une autre approche de marquage. Nous avons imaginé pour cela d'inclure un chélate fort du 99mTc dans le cycle tropane. Cette approche implique la construction complète du cycle tropane avec la présence de fonctions permettant l'insertion du système complexant. La synthèse de nouveaux dérivés du tropane a été réalisée et les structures originales obtenues ont ouvert de nouvelles et nombreuses perspectives.GRENOBLE1-BU Sciences (384212103) / SudocSudocFranceF

Synthèse de dérivés fonctionnalisés du 8-méthyl-8-azabicyclo[3.2.1]octane (vers de nouveaux marqueurs technétiés des transporteurs des monoamines)

GRENOBLE1-BU Sciences (384212103) / SudocSudocFranceF

Evolution of GPR regulation in the control of spindle positioning for two Caenorhabditis species embryos

International audienceno abstrac

Prevalence and Costs of Parkinsonian Syndromes Associated with Orthostatic Hypotension

Objective: To measure the frequency of and direct costs related to parkinsonian syndromes associated with orthostatic hypotension (OH). Patients/Methods: Patients over 45 years using at least one antiparkinsonian drug (excluding piribedil or anticholinergics prescribed alone) were identified from the Haute-Garonne Social Security prescription database and separated in two groups according to simultaneous prescription (OH group) or not (control group) of drugs for orthostatic hypotension. Direct medical costs were analysed retrospectively, over a 6-month period, from the health care payer's perspective. Results: Eighty-eight patients (9.1%) out of 971 parkinsonian also received antihypotensive drugs. Direct medical costs were significantly higher in OH than in control group (4.425 vs. 3.074 €/patient/6 months, p< 0.05). Beside hospitalisation and ancillary cares, drugs accounted for highest expenses (989 vs. 781 €/patient/6 months in control group) since use of controlled-release levodopa formulations or dopamine agonists was higher in OH group. Conclusion: Occurrence of OH is associated with higher medical expenditure in parkinsonian syndromes