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Charged multivesicular body protein 2B (CHMP2B) - a component of the endosomal complex required for transport-III (ESCRT-III) - is responsible for the vital membrane deformation functions in autophagy and endolysosomal trafficking. A dominant mutation in CHMP2B (CHMP2BIntron5) is associated with a subset of heritable frontotemporal dementia - frontotemporal dementia linked to chromosome 3 (FTD-3). ESCRT-III recruits Vps4, an AAA-ATPase that abscises the membrane during various cellular processes including autophagy and intraluminal vesicle formation. CHMP2BIntron5 results in a C-terminus truncation removing an important Vps4 binding site as well as eliminating the normal autoinhibitory resting state of CHMP2B. CHMP2B is expressed in most cell types but seems to be especially vital for proper neuronal function. CHMP2BIntron5-mediated phenotypes include misregulation of transmembrane receptors, accumulation of multilamellar structures, abnormal lysosomal morphology, down regulation of a brain-specific micro RNA (miRNA-124), abnormal dendritic spine morphology, decrease in dendritic arborization, and cell death. Currently, transgenic-fly,-mouse, and -human cell lines are being used to better understand the diverse phenotypes and develop therapeutic approaches for the CHMP2BIntron5-induced FTD-3. This article is part of a Special Issue entitled SI:Autophagy.

Resume Introduction Le but de cette etude etait de comparer deux strategies de relais en termes de performance, de reponses physiologiques et de perception de l’effort lors d’un contre-la-montre (CLM) cycliste par equipe. Synthese des faits Une meilleure performance est realisee lors du CLM en ligne (CLM-L) que lors du CLM en double ligne (CLM-DL) (42,0 vs 40,5 km/h). La puissance moyenne (78,5 ± 2,2 vs 74,5 ± 2,5 % PMA) ainsi que la FC moyenne (88,5 ± 2,2 vs 86,0 ± 1,9 % FCmax) sont significativement plus elevees lors du CLM-L compare au CLM-DL (p Conclusion En termes de performance, le CLM-L est plus efficace mais semble aussi plus eprouvant que le CLM-DL. Ainsi, ces deux modalites sont interessantes en competition mais nourrissent des ambitions differentes.

The emission of multi-component waves by sources in non-uniform media of arbitrary spatial dimension is discussed. If the emission occurs in the vicinity of a mode conversion region, i.e. a region where the local dispersion relations for two polarizations become nearly degenerate, the far field is very complex. The special case of plane-wave sources can be analyzed in detail and it is shown that the qualitative nature of the far field is completely determined by the ray geometry of the uncoupled modes. If the source is tunable, then, by varying the source and observing the associated changes in the emitted waves, one can extract a great deal of information about the background medium.