The Naturally Processed CD95L Elicits a c-Yes/Calcium/PI3K-Driven Cell Migration Pathway

Patients affected by chronic inflammatory disorders display high amounts of soluble CD95L. This homotrimeric ligand arises from the cleavage by metalloproteases of its membrane-bound counterpart, a strong apoptotic inducer. In contrast, the naturally processed CD95L is viewed as an apoptotic antagonist competing with its membrane counterpart for binding to CD95. Recent reports pinpointed that activation of CD95 may attract myeloid and tumoral cells, which display resistance to the CD95-mediated apoptotic signal. However, all these studies were performed using chimeric CD95Ls (oligomerized forms), which behave as the membrane-bound ligand and not as the naturally processed CD95L. Herein, we examine the biological effects of the metalloprotease-cleaved CD95L on CD95-sensitive activated T-lymphocytes. We demonstrate that cleaved CD95L (cl-CD95L), found increased in sera of systemic lupus erythematosus (SLE) patients as compared to that of healthy individuals, promotes the formation of migrating pseudopods at the leading edge of which the death receptor CD95 is capped (confocal microscopy). Using different migration assays (wound healing/Boyden Chamber/endothelial transmigration), we uncover that cl-CD95L promotes cell migration through a c-yes/Ca2+/PI3K-driven signaling pathway, which relies on the formation of a CD95-containing complex designated the MISC for Motility-Inducing Signaling Complex. These findings revisit the role of the metalloprotease-cleaved CD95L and emphasize that the increase in cl-CD95L observed in patients affected by chronic inflammatory disorders may fuel the local or systemic tissue damage by promoting tissue-filtration of immune cells

Rôles de la modulation des couplages électriques dans la reconfiguration des réseaux adultes et au cours de l'ontogénèse (approches moléculaire, neuroanatomique et électrophysiologique sur les réseaux du système nerveux stomatogastrique du homard breton)

Le système nerveux stomatogastrique du homard est un modèle particulièrement adapté à l étude de l implication de la modulation des synapses électriques dans l expression des réseaux neuronaux. En effet, la trentaine de neurones situés dans le ganglion stomatogastrique (STG) s organisent en deux réseaux distincts chez l adulte et un seul réseau chez l'embryon. Les activités générées par ces réseaux sont profondément remodelées lors de la mise en jeu de neurones modulateurs chez l adulte et lors de l ontogenèse. Au cours de ce travail, nous nous sommes intéressés aux modifications du couplage électrique et métabolique entre les neurones du STG au cours de ces reconfigurations. Nous avons démontré : -que, chez l adulte, la plupart des neurones du STG sont susceptibles de former des synapses électriques, donnant lieu à un couplage intra- et inter-réseau, -que la reconfiguration des deux réseaux adultes en un réseau unique par une paire de neurones modulateurs diminue l'étendue et la force des couplages électriques aussi bien intra- qu'inter-réseaux, -que la reconfiguration des deux réseaux adultes en un réseau unique par déplétion du GABA augmente l'étendue des couplages électriques aussi bien intra- qu'inter-réseaux et qu'au contraire l'apparition de GABA au cours du développement pourrait induire une diminution des couplages électriques conduisant à l'expression des réseaux adultes. Ces données montrent que la reconfiguration des réseaux neuronaux via l'action de substances neuromodulatrices fait intervenir des modifications de la force et de l étendue des couplages électriques ce qui pourrait permettre de modifier la hiérarchie des interactions entre neurones.BORDEAUX1-BU Sciences-Talence (335222101) / SudocSudocFranceF

Influence des oxydes d'espacement et des LDDs sur la réponse à la dose ionisante pour des MOSFETs fonctionnant à températures cryogéniques

International audienceIn this work, the radiation responses of 0.25 μm bulk transistors irradiated up to 300 krad are discussed. The electricals characteristics shown are measured after irradiation at 95 K, 150 K, and 300 K. The transconductance improves significantly with total ionizing dose (TID) at low temperature and does not vary at room temperature. The impact of incomplete ionization of impurities introduced into the Lightly Doped Drain extensions is examined. Since the transconductance increase is more pronounced for the shortest transistors, positive charges trapped in spacer oxides are likely to constitute the source of this increase. The Technology Computer-Aided Design simulations help us to discuss the influence of charge build-up at the spacers' locations on the drain to source resistance. By the means of a resistivity analysis, the influence of LDD doping level and operating temperature on the TID response of devices is analyzed. Its potential evolution with technological integration is investigated

Correction: The Naturally Processed CD95L Elicits a c-Yes/Calcium/PI3K-Driven Cell Migration Pathway.

[This corrects the article DOI: 10.1371/journal.pbio.1001090.]

HIV Protease Inhibitors Cure Lupus-Prone Mice and Prevent T Helper 17 Cell-Driven Inflammation By Inhibiting CD95-Non-Apoptotic Signaling Pathway

International audienc

Spatial variation of PM elemental composition between and within 20 European study areas : results of the ESCAPE project

An increasing number of epidemiological studies suggest that adverse health effects of air pollution may be related to particulate matter (PM) composition, particularly trace metals. However, we lack comprehensive data on the spatial distribution of these elements. We measured PM2.5 and PM10 in twenty study areas across Europe in three seasonal two-week periods over a year using Harvard impactors and standardized protocols. In each area, we selected street (ST), urban (UB) and regional background (RB) sites (totaling 20) to characterize local spatial variability. Elemental composition was determined by energy-dispersive X-ray fluorescence analysis of all PM2.5 and PM10 filters. We selected a priori eight (Cu, Fe, K, Ni, S, Si, V, Zn) well-detected elements of health interest, which also roughly represented different sources including traffic, industry, ports, and wood burning. PM elemental composition varied greatly across Europe, indicating different regional influences. Average street to urban background ratios ranged from 0.90 (V) to 1.60 (Cu) for PM2.5 and from 0.93 (V) to 2.28 (Cu) for PM10. Our selected PM elements were variably correlated with the main pollutants (PM2.5, PM10, PM2.5 absorbance, NO2 and NOx) across Europe: in general, Cu and Fe in all size fractions were highly correlated (Pearson correlations above 0.75); Si and Zn in the coarse fractions were modestly correlated (between 0.5 and 0.75); and the remaining elements in the various size fractions had lower correlations (around 0.5 or below). This variability in correlation demonstrated the distinctly different spatial distributions of most of the elements. Variability of PM10_Cu and Fe was mostly due to within-study area differences (67% and 64% of overall variance, respectively) versus between-study area and exceeded that of most other traffic-related pollutants, including NO2 and soot, signaling the importance of non-tailpipe (e.g., brake wear) emissions in PM

Spatial variation of PM elemental composition between and within 20 European study areas - results of the ESCAPE project

An increasing number of epidemiological studies suggest that adverse health effects of air pollution may be related to particulate matter (PM) composition, particularly trace metals. However, we lack comprehensive data on the spatial distribution of these elements. We measured PM2.5 and PM10 in twenty study areas across Europe in three seasonal two-week periods over a year using Harvard impactors and standardized protocols. In each area, we selected street (ST), urban (UB) and regional background (RB) sites (totaling 20) to characterize local spatial variability. Elemental composition was determined by energy-dispersive X-ray fluorescence analysis of all PM2.5 and PM10 filters. We selected a priori eight (Cu, Fe, K, Ni, S, Si, V, Zn) well-detected elements of health interest, which also roughly represented different sources including traffic, industry, ports, and wood burning. PM elemental composition varied greatly across Europe, indicating different regional influences. Average street to urban background ratios ranged from 0.90 (V) to 1.60 (Cu) for PM2.5 and from 0.93 (V) to 2.28 (Cu) for PM10. Our selected PM elements were variably correlated with the main pollutants (PM2.5, PM10, PM2.5 absorbance, NO2 and NOx) across Europe: in general, Cu and Fe in all size fractions were highly correlated (Pearson correlations above 0.75); Si and Zn in the coarse fractions were modestly correlated (between 0.5 and 0.75); and the remaining elements in the various size fractions had lower correlations (around 0.5 or below). This variability in correlation demonstrated the distinctly different spatial distributions of most of the elements. Variability of PM10_Cu and Fe was mostly due to within-study area differences (67% and 64% of overall variance, respectively) versus between-study area and exceeded that of most other traffic-related pollutants, including NO2 and soot, signaling the importance of non-tailpipe [...]Aplinkotyros katedraVytauto Didžiojo universiteta