ET-1 and NOS III gene expression regulation by plaque-free and plaque-prone hemodynamic conditions

Résumé: Les environnements hémodynamiques, favorisant ou protégeant contre la formation de la plaque, induisent tout deux une augmentation de la production d'anion superoxide dans les cellules endothéliales (ECs). Par ailleurs, une régulation différente de l'expression des gènes a été décrite dans les cellules exposées à ces différentes conditions. Dans le but d'investiguer le rôle de l'augmentation du stress oxydatif dans l'expression des gènes régulée par le flux, nous avons d'abord exposé les EC à un flux unidirectionnel, non pulsé. Dans ces conditions, l'état oxydatif des cellules endothéliales est augmenté de façon transitoire. L'expression du gène de l'endothéline 1 (ET-1) est aussi induite de façon transitoire par un tel flux, alors que l'expression du gène de la nitiric oxyde synthase endothéliale (NOS III) est stimulé de façon durable. Au contraire, un flux unidirectionnel pulsé, qui induit une augmentation durable de la production d'anion superoxide, augmente aussi de façon durable l'expression des gènes de ET-1 comme de NOS III. Un flux oscillatoire (favorisant la plaque), qui lui aussi ,a des effets à long terme sur la production d'anion superoxide, a uniquement augmenté l'expression de ET-1. De plus, l'utilisation d'un antioxydant, a seulement partiellement inhibé la stimulation de l'expression du gène NOS III par le flux unidirectionnel pulsé, alors qu'il a complètement abrogé la stimulation de l'expression du gène ET-1 par le flux unidirectionnel pulsé et oscillatoire. Ceci suggère que les forces mécaniques régulent l'expression des gènes dans les EC par un double mécanisme dépendant et indépendant du stress oxidatif des cellules. Par ailleurs, ces résultats supportent ultérieurement l'hypothèse que la balance entre la réponse oxidative et anti-oxidante dans les cellules endothéliales exposées à un environnement hémodynamique est une des clés de la prédisposition à un dysfonctionnement endothélial observé dans des régions exposées à des flux perturbés. Abstract: Both plaque-free and plaque-prone hemodynamic environments induce an increase in the oxidative state of endothelial cells (ECs), whereas differential gene expression regulation was described in cells exposed to these conditions. In order to investigate the role of the increased oxidative state in flow-regulation of gene expression, we first exposed EC to non-pulsed unidirectional shear stress. These conditions only slightly increases ECs oxidative state and endothelin-1 (ET-1) mRNA expression, whereas endothelial nitric oxide synthase (NOS III) mRNA level were significantly up-regulated. On the contrary, both ET-1 and NOS III gene expression were significantly induced in EC exposed to pulsed-unidirectional flow (plaque-free). Only ET-1 gene expression was up-regulated by oscillatory flow (plaque-prone). Moreover, use of an antioxidant only partially inhibited NOS III gene up-regulation by unidirectional flow, whereas it completely abrogated ET-1 gene up-regulation by unidirectional and oscillatory flows. Thus suggesting that mechanical forces regulate gene expression in ECs both via oxidative stress-dependent and -independent mechanisms.

Occurrence of common scab in potato tubers following foliar treatment with glycinebetaine under glasshouse conditions

Selostus: Glysiinibetaiinilla suoritetun lehvästöruiskutuken vaikutus perunan rupisuuteen

Reproductive and post-reproductive life history of wild-caught Drosophila melanogaster under laboratory conditions.

The life history of the fruit fly (Drosophila melanogaster) is well understood, but fitness components are rarely measured by following single individuals over their lifetime, thereby limiting insights into lifetime reproductive success, reproductive senescence and post-reproductive lifespan. Moreover, most studies have examined long-established laboratory strains rather than freshly caught individuals and may thus be confounded by adaptation to laboratory culture, inbreeding or mutation accumulation. Here, we have followed the life histories of individual females from three recently caught, non-laboratory-adapted wild populations of D. melanogaster. Populations varied in a number of life-history traits, including ovariole number, fecundity, hatchability and lifespan. To describe individual patterns of age-specific fecundity, we developed a new model that allowed us to distinguish four phases during a female's life: a phase of reproductive maturation, followed by a period of linear and then exponential decline in fecundity and, finally, a post-ovipository period. Individual females exhibited clear-cut fecundity peaks, which contrasts with previous analyses, and post-peak levels of fecundity declined independently of how long females lived. Notably, females had a pronounced post-reproductive lifespan, which on average made up 40% of total lifespan. Post-reproductive lifespan did not differ among populations and was not correlated with reproductive fitness components, supporting the hypothesis that this period is a highly variable, random 'add-on' at the end of reproductive life rather than a correlate of selection on reproductive fitness. Most life-history traits were positively correlated, a pattern that might be due to genotype by environment interactions when wild flies are brought into a novel laboratory environment but that is unlikely explained by inbreeding or positive mutational covariance caused by mutation accumulation.

Influence of the menstrual cycle on the sweating response measured by direct calorimetry in women exposed to warm environmental conditions.

The whole body sweating response was measured at rest in eight women during the follicular (F) and the luteal (L) phases of the menstrual cycle. Subjects were exposed for 30-min to neutral (N) environmental conditions [ambient temperature (Ta) 28 degrees C] and then for 90-min to warm (W) environmental conditions (Ta, 35 degrees C) in a direct calorimeter. At the end of the N exposure, tympanic temperature (Tty) was 0.18 (SEM 0.06) degrees C higher in the L than in the F phase (P less than 0.05), whereas mean skin temperature (Tsk) was unchanged. During W exposure, the time to the onset of sweating as well as the concomitant increase in body heat content were similar in both phases. At the onset of sweating, the tympanic threshold temperature (Tty,thresh) was higher in the L phase [37.18 (SEM 0.08) degrees C] than in the F phase [36.95 (SEM 0.07) degrees C; P less than 0.01]. The magnitude of the shift in Tty,thresh [0.23 (SEM 0.07) degrees C] was similar to the L-F difference in Tty observed at the end of the N exposure. The mean skin threshold temperature was not statistically different between the two phases. The slope of the relationship between sweating rate and Tty was similar in F and L. It was concluded that the internal set point temperature of resting women exposed to warm environmental conditions shifted to a higher value during the L phase compared to the F phase of the menstrual cycle; and that the magnitude of the shift corresponded to the difference in internal temperature observed in neutral environmental conditions between the two phases.

Statistical analysis and modelling of weather radar beam propagation conditions in the Po Valley (Italy)

Ground clutter caused by anomalous propagation (anaprop) can affect seriously radar rain rate estimates, particularly in fully automatic radar processing systems, and, if not filtered, can produce frequent false alarms. A statistical study of anomalous propagation detected from two operational C-band radars in the northern Italian region of Emilia Romagna is discussed, paying particular attention to its diurnal and seasonal variability. The analysis shows a high incidence of anaprop in summer, mainly in the morning and evening, due to the humid and hot summer climate of the Po Valley, particularly in the coastal zone. Thereafter, a comparison between different techniques and datasets to retrieve the vertical profile of the refractive index gradient in the boundary layer is also presented. In particular, their capability to detect anomalous propagation conditions is compared. Furthermore, beam path trajectories are simulated using a multilayer ray-tracing model and the influence of the propagation conditions on the beam trajectory and shape is examined. High resolution radiosounding data are identified as the best available dataset to reproduce accurately the local propagation conditions, while lower resolution standard TEMP data suffers from interpolation degradation and Numerical Weather Prediction model data (Lokal Model) are able to retrieve a tendency to superrefraction but not to detect ducting conditions. Observing the ray tracing of the centre, lower and upper limits of the radar antenna 3-dB half-power main beam lobe it is concluded that ducting layers produce a change in the measured volume and in the power distribution that can lead to an additional error in the reflectivity estimate and, subsequently, in the estimated rainfall rate.

Comment dépister les syndromes gériatriques au cabinet [How to screen geriatric conditions in primary care?].

The ongoing aging of the population will lead to an increasing prevalence of chronic diseases and functional limitation. Preventative measures need to be promoted to prevent health care utilization and health costs explosion. Among these measures, those aimed at promoting early recognition of chronic conditions associated with functional decline, will have to be reinforced. This paper proposes simple, feasible, and efficient procedures to screen, in primary care practices, common geriatric conditions, as cognitive impairment, gait impairment, hearing and vision impairment or functional limitation.

Conditional BDNF release under pathological conditions improves Huntington's disease pathology by delaying neuronal dysfunction

Background Brain-Derived Neurotrophic Factor (BDNF) is the main candidate for neuroprotective therapy for Huntington's disease (HD), but its conditional administration is one of its most challenging problems. Results Here we used transgenic mice that over-express BDNF under the control of the Glial Fibrillary Acidic Protein (GFAP) promoter (pGFAP-BDNF mice) to test whether up-regulation and release of BDNF, dependent on astrogliosis, could be protective in HD. Thus, we cross-mated pGFAP-BDNF mice with R6/2 mice to generate a double-mutant mouse with mutant huntingtin protein and with a conditional over-expression of BDNF, only under pathological conditions. In these R6/2:pGFAP-BDNF animals, the decrease in striatal BDNF levels induced by mutant huntingtin was prevented in comparison to R6/2 animals at 12 weeks of age. The recovery of the neurotrophin levels in R6/2:pGFAP-BDNF mice correlated with an improvement in several motor coordination tasks and with a significant delay in anxiety and clasping alterations. Therefore, we next examined a possible improvement in cortico-striatal connectivity in R62:pGFAP-BDNF mice. Interestingly, we found that the over-expression of BDNF prevented the decrease of cortico-striatal presynaptic (VGLUT1) and postsynaptic (PSD-95) markers in the R6/2:pGFAP-BDNF striatum. Electrophysiological studies also showed that basal synaptic transmission and synaptic fatigue both improved in R6/2:pGAP-BDNF mice. Conclusions These results indicate that the conditional administration of BDNF under the GFAP promoter could become a therapeutic strategy for HD due to its positive effects on synaptic plasticity.