Lysosomal enzyme precursors in coated vesicles derived from the exocytic and endocytic pathways.

The molecular forms of two lysosomal enzymes, cathepsin C and cathepsin D, have been examined in lysosomes and coated vesicles (CVs) of rat liver. In addition, the relative proportion of these lysosomal enzymes residing in functionally distinct CV subpopulations was quantitated. CVs contained newly synthesized precursor forms of the enzymes in contrast to lysosomes where only the mature forms were detected. Exocytic and endocytic CV subpopulations were prepared by two completely different protocols. One procedure, a density shift method, uses cholinesterase to alter the density of CVs derived from exocytic or endocytic pathways. The other relies on electrophoretic heterogeneity to accomplish the CV subfractionation. Subpopulations of CVs prepared by either procedure showed similar results, when examined for their relative proportion of cathepsin C and cathepsin D precursors. Within the starting CV preparation, exocytic CVs contained approximately 80-90% of the total steady-state levels of these enzymes while the level in the endocytic population was approximately 10-13%. The implications of these findings are discussed with regard to lysosome trafficking

Multi-objective Optimization under Uncertainty using the Hyper-volume Expected Improvement

The design of real engineering systems requires the optimization of multiple quantities of interest. In the electric motor design, one wants to maximize the average torque and minimize the torque variation. A study has shown that these attributes vary for different geometries of the rotor teeth. However, simulations of a large number of designs cannot be performed due to their high cost. In many problems, design optimization of multi-objective functions is a very challenging task due to the difficulty to evaluate the expectation of the objectives. Current multi-objective optimization (MOO) techniques, e.g., evolutionary algorithms cannot solve such problems because they require hundreds of thousands of function evaluations. Therefore, an alternative methodology must be used to identify a Pareto front, a set of optimal designs of MOO. Recent extensions of Bayesian global optimization are able to do exactly that. The idea is to replace the expensive objective functions with cheap-to-evaluate probabilistic surrogates trained using few input-output pairs and to sequentially query designs that maximize the improvement of the Pareto front. For these purposes, we developed SMOOT, a Rappture tool built on a NanoHUB platform. It enables experimentalists to optimize their expensive processes without a need to understand the optimization methodology and guides them to make better decisions in order to find optimal designs

The RMS Survey: Ammonia and water maser analysis of massive star forming regions

The Red MSX Source (RMS) survey has identified a sample of ~1200 massive young stellar objects (MYSOs), compact and ultra compact HII regions from a sample of ~2000 MSX and 2MASS colour selected sources. We have used the 100 m Green Bank telescope to search for 22-24 GHz water maser and ammonia (1,1), (2,2) and (3,3) emission towards ~600 RMS sources located within the northern Galactic plane. We have identified 308 H2O masers which corresponds to an overall detection rate of ~50%. Abridged: We detect ammonia emission towards 479 of these massive young stars, which corresponds to ~80%. Ammonia is an excellent probe of high density gas allowing us to measure key parameters such as gas temperatures, opacities, and column densities, as well as providing an insight into the gas kinematics. The average kinetic temperature, FWHM line width and total NH3 column density for the sample are approximately 22 K, 2 km/s and 2x10^{15} cm^{-2}, respectively. We find that the NH3 (1,1) line width and kinetic temperature are correlated with luminosity and finding no underlying dependence of these parameters on the evolutionary phase of the embedded sources, we conclude that the observed trends in the derived parameters are more likely to be due to the energy output of the central source and/or the line width-clump mass relationship. The velocities of the peak H2O masers and the NH3 emission are in excellent agreement with each other, which would strongly suggest an association between the dense gas and the maser emission. Moreover, we find the bolometric luminosity of the embedded source and the isotropic luminosity of the H2O maser are also correlated. We conclude from the correlations of the cloud and water maser velocities and the bolometric and maser luminosity that there is a strong dynamical relationship between the embedded young massive star and the H2O maser.Comment: 17 pages and 17 figures and 8 tables. Tables\,2 and 5 and full versions of Figs. 3 and 7 are only available in electronic form at the CDS via anonymous ftp to cdsarc.u-strasbg.fr (130.79.125.5) or via http://cdsweb.u-strasbg.fr/cgi-bin/qcat?J/A+A

Sod2 haploinsufficiency does not accelerate aging of telomere dysfunctional mice

Telomere shortening represents a causal factor of cellular senescence. At the same time, several lines of evidence indicate a pivotal role of oxidative DNA damage for the aging process in vivo. A causal connection between the two observations was suggested by experiments showing accelerated telomere shorting under conditions of oxidative stress in cultured cells, but has never been studied in vivo. We therefore have analysed whether an increase in mitochondrial derived oxidative stress in response to heterozygous deletion of superoxide dismutase (Sod2+/-) would exacerbate aging phenotypes in telomere dysfunctional (mTerc-/-) mice. Heterozygous deletion of Sod2 resulted in reduced SOD2 protein levels and increased oxidative stress in aging telomere dysfunctional mice, but this did not lead to an increase in basal levels of oxidative nuclear DNA damage, an accumulation of nuclear DNA breaks, or an increased rate of telomere shortening in the mice. Moreover, heterozygous deletion of Sod2 did not accelerate the depletion of stem cells and the impairment in organ maintenance in aging mTerc-/- mice. In agreement with these observations, Sod2 haploinsufficiency did not lead to a further reduction in lifespan of mTerc-/- mice. Together, these results indicate that a decrease in SOD2-dependent antioxidant defence does not exacerbate aging in the context of telomere dysfunction