Depletion of SMN by RNA interference in HeLa cells induces defects in Cajal body formation

Neuronal degeneration in spinal muscular atrophy (SMA) is caused by reduced expression of the survival of motor neuron (SMN) protein. The SMN protein is ubiquitously expressed and is present both in the cytoplasm and in the nucleus where it localizes in Cajal bodies. The SMN complex plays an essential role for the biogenesis of spliceosomal U-snRNPs. In this article, we have used an RNA interference approach in order to analyse the effects of SMN depletion on snRNP assembly in HeLa cells. Although snRNP profiles are not perturbed in SMN-depleted cells, we found that SMN depletion gives rise to cytoplasmic accumulation of a GFP-SmB reporter protein. We also demonstrate that the SMN protein depletion induces defects in Cajal body formation with coilin being localized in multiple nuclear foci and in nucleolus instead of canonical Cajal bodies. Interestingly, the coilin containing foci do not contain snRNPs but appear to co-localize with U85 scaRNA. Because Cajal bodies represent the location in which snRNPs undergo 2′-O-methylation and pseudouridylation, our results raise the possibility that SMN depletion might give rise to a defect in the snRNA modification process

Back-supported stratified flame propagation in lean and nonflammable mixtures

International audienceIn an effort to reduce pollutant emissions and increase energy efficiency, partially premixed combustion has been integrated into many new combustion technologies. The present study investigated lean back-supported flames in a stratified combustion regime. Outwardly propagating flames were observed following ignition under laminar stratification conditions generated in a constant volume vessel. The quantitative analysis of the flame properties relied on simultaneous PIV measurements to obtain local flame burning velocities and stretch rates and used anisole-PLIF measurements to calculate the equivalence ratio. Simultaneous OH-PLIF and OH-gradient measurements were used to differentiate between the burned gas boundaries and the active flame front. This differentiation was necessary to investigate the nonflammable mixture. Simultaneous OH-and anisole-PLIF measurements were used to estimate the thermal flame thickness. Two flame families were investigated: in family A the flame was ignited in a lean mixture (φ=0.6) with a rich stratification; in family B the mixture in the chamber was nonflammable. In rich mixtures ignition compensated for the non-equidiffusive effects of the lean propane flame. Both a flammable and a nonflammable mixture were investigated to evaluate the time scales of the back-supported propagation for the given stratification. The enhanced combustion regime allowed the flame to propagate with an active flame front, even in the nonflammable mixture for a few milliseconds before the flame extinguished

Human telomerase RNA and box H/ACA scaRNAs share a common Cajal body–specific localization signal

Telomerase is a ribonucleoprotein reverse transcriptase that uses its RNA component as a template for synthesis of telomeric DNA repeats at the ends of linear eukaryotic chromosomes. Here, fluorescence in situ hybridization demonstrates that in HeLa cancer cells, human telomerase RNA (hTR) accumulates in the nucleoplasmic Cajal bodies (CBs). Localization of transiently expressed hTR to CBs is supported by a short sequence motif (411-UGAG-414) that is located in the 3′-terminal box H/ACA RNA-like domain of hTR and that is structurally and functionally indistinguishable from the CB-specific localization signal of box H/ACA small CB-specific RNAs. In synchronized HeLa cells, hTR shows the most efficient accumulation in CBs during S phase, when telomeres are most likely synthesized. CBs may function in post-transcriptional maturation (e.g., cap hypermethylation of hTR), but they may also play a role in the assembly and/or function of telomerase holoenzyme

Simulation numérique de la condensation / évaporation et de la coagulation des nanoparticules

National audienceAware of the risks related to nanoparticles (particles which present at least one dimension less than 100 nanometers), INERIS decided in 2009 to create a research program in order to develop a model that would be able to simulate the dynamic of nanoparticles in both confined and free atmospheres. The distinction with usual models is that we need to follow the evolution of the number of particles together with their the mass : in order to simulate the evolution of nanoparticles, the number is much more relevant. A comparative review of algorithms currently used in air quality models and new algorithms adapted to nanoparticles is presented. This first study addresses condensational growth, evaporation and coagulation. The model is to be integrated in chemistry-transport models (CHIMERE) and in CFD models (code_Saturne EdF).Conscient des risques liés aux nanoparticules (particules dont au moins une des dimensions est inférieure à 100 nanomètres), l'INERIS(1) a engagé en 2009 un programme de recherche en collaboration avec le CEREA(2) afin de développer un modèle capable de simuler les transformations des nanoparticules dans les ambiances intérieures (espaces confinés) comme dans l'atmosphère. En effet, les nanoparticules sont notamment susceptibles de coaguler, de grossir par condensation, et de se déposer sur les parois; ce qui modifie leur granulométrie. Une des problématiques liée à la modélisation des nanoparticules est que leur nombre est déterminant devant leur masse, tout au contraire des particules étudiées jusqu'à présent (particules fines ou grossières dont une des dimensions est supérieure à 100 nanomètre). Différents schémas numériques ont été développés pour simuler la condensation/évaporation d'une population de particules, et un noyau de coagulation issu d'algorithmes usuels a été intégré. L'inter-comparaison de ces schémas met en évidence que certains sont plus adaptés que d'autres pour les nanoparticules. Les algorithmes qui sont appropriés pour toutes les tailles de particules sont présentés. A terme, ce modèle de dynamique des nanoparticules a vocation à être intégré dans des modèles de dispersion atmosphérique (CHIMERE) et des modèles CFD (code_Saturne EdF

Programming implantable cardioverter-defibrillators in primary prevention: Higher or later

SummaryDefibrillator shocks, appropriate or not, are associated with significant morbidity, as they decrease quality of life, can be involved in depression and anxiety, and are known to be proarrhythmic. Most recent data have even shown an association between shocks and overall mortality. As opposed to other defibrillator-related complications, the rate of inappropriate and unnecessary shocks can (and should) be decreased with adequate programming. This review focuses on the different programming strategies and tips available to reduce the rate of shocks in primary prevention patients with left ventricular dysfunction implanted with a defibrillator, as well as some of the manufacturers’ device specificities