Structure of Mycobacterium smegmatis single-stranded DNA-binding protein and a comparative study involving homologus SSBs: biological implications of structural plasticity and variability in quaternary association

The structure of Mycobacterium smegmatis single-stranded DNA-binding protein (SSB) has been determined using three data sets collected from related crystals. The structure is similar to that of its homologue from Mycobacterium tuberculosis, indicating that the clamp arrangement that stabilizes the dimer and the ellipsoidal shape of the tetramer are characteristic features of mycobacterial SSBs. The central OB fold is conserved in mycobacterial SSBs as well as those from Escherichia coli, Deinococcus radiodurans and human mitochondria. However, the quaternary structure exhibits considerable variability. The observed plasticity of the subunit is related to this variability. The crystal structures and modelling provide a rationale for the variability. The strand involved in the clamp mechanism, which leads to higher stability of the tetramer, appears to occur in all high-G+C Gram-positive bacteria. The higher stability is perhaps required by these organisms. The mode of DNA binding of mycobacterial SSBs is different from that of E. coli SSB partly on account of the difference in the shape of the tetramers. Another difference between the two modes is that the former contains additional ionic interactions and is more susceptible to salt concentration

BAY61-3606 Affects the Viability of Colon Cancer Cells in a Genotype-Directed Manner

Background: K-RAS mutation poses a particularly difficult problem for cancer therapy. Activating mutations in K-RAS are common in cancers of the lung, pancreas, and colon and are associated with poor response to therapy. As such, targeted therapies that abrogate K-RAS-induced oncogenicity would be of tremendous value. Methods: We searched for small molecule kinase inhibitors that preferentially affect the growth of colorectal cancer cells expressing mutant K-RAS. The mechanism of action of one inhibitor was explored using chemical and genetic approaches. Results: We identified BAY61-3606 as an inhibitor of proliferation in colorectal cancer cells expressing mutant forms of K-RAS, but not in isogenic cells expressing wild-type K-RAS. In addition to its anti-proliferative effects in mutant cells, BAY61-3606 exhibited a distinct biological property in wild-type cells in that it conferred sensitivity to inhibition of RAF. In this context, BAY61-3606 acted by inhibiting MAP4K2 (GCK), which normally activates NFκβ signaling in wild-type cells in response to inhibition of RAF. As a result of MAP4K2 inhibition, wild-type cells became sensitive to AZ-628, a RAF inhibitor, when also treated with BAY61-3606. Conclusions: These studies indicate that BAY61-3606 exerts distinct biological activities in different genetic contexts

Non-similar solutions for unsteady flow over a yawed cylinder with non-uniform mass transfer through a slot

Non-similar solutions are found numerically to a system of coupled non-linear partial differential equations indicating, unsteady laminar water boundary layer flow over yawed cylinder using implicit finite difference scheme along with Quasi-linearization technique. The fluid properties such as viscosity and Prandtl number are considered as an inverse function of temperature. Unsteadiness is caused by upstream velocity in and directions and non-uniform mass transfer (suction/injection) which is applied through slot on the surface of the geometry. The effect of yaw angle, variable fluid properties and non-uniform mass transfer on skin friction and heat transfer coefficients is analyzed. It is found that non-uniform slot suction and downstream movement of the slot cause the point of vanishing skin friction moves downstream, but non-uniform slot injection produces the opposite result of that corresponding to the suction case. When the yaw angle increases, both the skin friction coefficient in the – direction and the heat transfer coefficient decrease but the skin friction coefficient in the – direction increases for all times. The effect of the yaw angle is very little on the point of vanishing skin friction

Influence of Bagasse/Sisal Fibre Stacking Sequence on the Mechanical Characteristics of Hybrid-Epoxy Composites

The current study deals with the mechanical and morphological properties of sisal/bagasse fibers reinforced epoxy composites. The composites were developed by the hand layup process in four different proportions of sisal/bagasse fibers. The produced composites were characterized for its mechanical characteristics, namely, tensile, flexural, impact, Shore D hardness compression tests, water absorption and biodegradation tests as per ASTM. Morphologies were studied using Scanning Electron Microscopy. It was inferred that composites with three layers of sisal fibers and a core layer of sisal fibers produced good properties