Actin sequestering protein, profilin, regulates intracellular vesicle transport in Leishmania

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On the Stability of Convection in a Non-Newtonian Vertical Fluid Layer in the Presence of Gold Nanoparticles: Drug Agent for Thermotherapy

We consider the effect of gold nanoparticles on the stability properties of convection in a vertical fluid layer saturated by a Jeffreys fluid. The vertical boundaries are rigid and hold at uniform but different temperatures. Brownian diffusion and thermophoresis effects are considered. Due to numerous applications in the biomedical industry, such a study is essential. The linear stability is investigated through the normal mode disturbances. The resulting stability problem is an eighth-order ordinary differential complex eigenvalue problem that is solved numerically using the Chebyshev collection method. Its solution provides the neutral stability curves, defining the threshold of linear instability, and the critical parameters at the onset of instability are determined for various values of control parameters. The results for Newtonian fluid and second-grade fluid are delineated as particular cases from the present study. It is shown that the Newtonian fluid has a more stabilizing effect than the second-grade and the Jeffreys fluids in the presence of gold nanoparticles and, Jeffreys fluid is the least stable

Synthetic Uncleavable Ubiquitinated Proteins Dissect Proteasome Deubiquitination and Degradation, and Highlight Distinctive Fate of Tetraubiquitin

Various hypotheses have been proposed regarding how chain length, linkage type, position on substrate, and susceptibility to deubiquitinases (DUBs) affect processing of different substrates by proteasome. Here we report a new strategy for the chemical synthesis of ubiquitinated proteins to generate a set of well-defined conjugates bearing an oxime bond between the chain and the substrate. We confirmed that this isopeptide replacement is resistant to DUBs and to shaving by proteasome. Analyzing products generated by proteasomes ranked how chain length governed degradation outcome. Our results support that (1) the cleavage of the proximal isopeptide bond is not a prerequisite for proteasomal degradation, (2) by overcoming trimming at the proteasome, tetraUb is a fundamentally different signal than shorter chains, and (3) the tetra-ubiquitin chain can be degraded with the substrate. Together these results highlight the usefulness of chemistry to dissect the contribution of proteasome-associated DUBs and the complexity of the degradation process

Discovery of 7-azaindole based anaplastic lymphoma kinase (ALK) inhibitors: Wild type and mutant (L1196M) active compounds with unique binding mode

We have identified a novel 7-azaindole series of anaplastic lymphoma kinase (ALK) inhibitors. Compounds 7h, 7m and 7n demonstrate excellent potencies in biochemical and cellular assays. X-ray crystal structure of one of the compounds (7k) revealed a unique binding mode with the benzyl group occupying the back pocket, explaining its potency towards ALK and selectivity over tested kinases particularly Aurora-A. This binding mode is in contrast to that of known ALK inhibitors such as Crizotinib and NVP-TAE684 which occupy the ribose binding pocket, close to DFG motif. (C) 2013 Elsevier Ltd. All rights reserved