Signalling mechanisms in Mycobacteria

The importance of inter-and intracellular signal transduction in all forms of life cannot be underestimated. A large number of genes dedicated to cellular signalling are found in almost all sequenced genomes, and Mycobacteria are no exception. What appears to be interesting in Mycobacteria is that well characterized signalling mechanisms used by bacteria, such as the histidine-aspartate phosphorelay seen in two-component systems, are found alongside signalling components that closely mimic those seen in higher eukaryotes. This review will describe the important contribution made by researchers in India towards the identification and characterization of proteins involved in two-component signalling, protein phosphorylation and cyclic nucleotide metabolism. (C) 2011 Elsevier Ltd. All rights reserved.

Structural basis for the functional and inhibitory mechanisms of beta-hydroxyacyl-acyl carrier protein dehydratase (FabZ) of Plasmodium falciparum

The beta-hydroxyacyl-acyl carrier protein dehydratase of Plasmodium falciparum (PfFabZ) catalyzes the third and important reaction of the fatty acid elongation cycle. The crystal structure of PfFabZ is available in hexameric (active) and dimeric (inactive) forms. However, PfFabZ has not been crystallized with any bound inhibitors until now. We have designed a new condition to crystallize PfFabZ with its inhibitors bound in the active site, and determined the crystal structures of four of these complexes. This is the first report on any FabZ enzyme with active site inhibitors that interact directly with the catalytic residues. Inhibitor binding not only stabilized the substrate binding loop but also revealed that the substrate binding tunnel has an overall shape of ``U''. In the crystal structures, residue Phe169 located in the middle of the tunnel was found to be in two different conformations, open and closed. Thus, Phe169, merely by changing its side chain conformation, appears to be controlling the length of the tunnel to make it suitable for accommodating longer substrates. The volume of the substrate binding tunnel is determined by the sequence as well as by the conformation of the substrate binding loop region and varies between organisms for accommodating fatty acids of different chain lengths. This report on the crystal structures of the complexes of PfFabZ provides the structural basis of the inhibitory mechanism of the enzyme that could be used to improve the potency of inhibitors against an important component of fatty acid synthesis common to many infectious organisms. (C) 2011 Elsevier Inc. All rights reserved.

A Kinematic Theory for Planar Hoberman and Other Novel Foldable Mechanisms

In this paper, we present a kinematic theory for Hoberman and other similar foldable linkages. By recognizing that the building blocks of such linkages can be modeled as planar linkages, different classes of possible solutions are systematically obtained including some novel arrangements. Criteria for foldability are arrived by analyzing the algebraic locus of the coupler curve of a PRRP linkage. They help explain generalized Hoberman and other mechanisms reported in the literature. New properties of such mechanisms including the extent of foldability, shape-preservation of the inner and outer profiles, multi-segmented assemblies and heterogeneous circumferential arrangements are derived. The design equations derived here make the conception of even complex planar radially foldable mechanisms systematic and easy. Representative examples are presented to illustrate the usage of the design equations and the kinematic theory.

An Objective Evaluation of Displacement-Amplifying Compliant Mechanisms for Sensor Applications

Displacement-amplifying compliant mechanisms (DaCMs) reported in literature are mostly used for actuator applications. This paper considers them for sensor applications that rely on displacement measurement, and evaluates them objectively. The main goal is to increase the sensitivity under constraints imposed by several secondary requirements and practical constraints. A spring-mass-lever model that effectively captures the addition of a DaCM to a sensor is used in comparing eight DaCMs. We observe that they significantly differ in performance criteria such as geometric advantage, stiffness, natural frequency, mode amplification, factor of safety against failure, cross-axis stiffness, etc., but none excel in all. Thus, a combined figure of merit is proposed using which the most suitable DaCM could be selected for a sensor application. A case-study of a micro machined capacitive accelerometer and another case-study of a vision-based force sensor are included to illustrate the general evaluation and selection procedure of DaCMs with specific applications. Some other insights gained with the analysis presented here were the optimum size-scale for a DaCM, the effect on its natural frequency, limits on its stiffness, and working range of the sensor.

Mechanisms of summer intraseasonal sea surface temperature oscillations in the Bay of Bengal

Intraseasonal variations (ISV) of sea surface temperature (SST) in the Bay of Bengal (BoB) is highest in its northwestern part. An Indian Ocean model forced by QuikSCAT winds and climatological river discharge (QR run) reproduces ISV of SST, albeit with weaker magnitude. Air-sea fluxes, in the presence of a shallow mixed layer, efficiently effect intraseasonal SST fluctuations. Warming during intraseasonal events is smaller (<1°C) for June - July period and larger (1.5° to 2°C) during September, the latter due to a thinner mixed layer. To examine the effect of salinity on ISV, the model was run by artificially increasing the salinity (NORR run) and by decreasing it (MAHA10 run). In NORR, both rainfall and river discharge were switched off and in MAHA10 the discharge by river Mahanadi was increased tenfold. The spatial pattern of ISV as well as its periodicity was similar in QR, NORR and MAHA10. The ISV was stronger in NORR and weaker in MAHA10, compared to QR. In NORR, both intraseasonal warming and cooling were higher than in QR, the former due to reduced air-sea heat loss as the mean SST was lower, and the latter due to enhanced subsurface processes resulting from weaker stratification. In MAHA10, both warming and cooling were lower than in QR, the former due to higher air-sea heat loss owing to higher mean SST, and the latter due to weak subsurface processes resulting from stronger stratification. These model experiments suggest that salinity effects are crucial in determining amplitudes of intraseasonal SST variations in the BoB.

On the mechanism of plastic flow at 86°k in quenched and aged aluminum

The plastic flow of quenched aluminium at 86°K was investigated by ‘differential-stress’ creep tests in order to evaluate the rate-controlling mechanism in as-quenched and fully aged states. The experimental values of activation volume (4·3 × 10−21 cm3 for as-quenched and 5·5×l0−21cm3 for fully aged) and the total energy for thermal activation process (0·4 ev for both) are in accordance with the jog hardening and loop hardening mechanisms in quenched and fully aged states respectively.

Dislocation mechanisms for plastic flow of nickel in the temperature range 4.2 – 1200 K

The temperature ranges of thermal and athermal deformation behaviour of nickel are identified by employing the temperature-dependence of flow-stress and strain-rate cycling data. The results are used to present a unified view of dislocation mechanisms of glide encompassing the two thermally activated and the intermediate athermal regimes of plastic flow.In the low-temperature thermally activated region (<250 K) the strain rate is found to be controlled by the repulsive intersection of glide and forest dislocations, in accordance with current ideas. The athermal stress in this region can be attributed mainly to the presence of strong attractive junctions which are overcome by means of Orowan bowing, a small contribution also coming from the elastic interactions between dislocations. The values of activation area and activation energy obtained in the high-temperature region (> 750 K) negate the operation of a diffusion-controlled mechanism. Instead, the data support a thermal activation model involving unzipping of the attractive junctions. The internal (long-range) stress contribution here results solely from the elastic interactions between dislocations. This view concerning the high-temperature plastic flow is further supported by the observation that the Cottrell–Stokes law is obeyed over large strains in the range 750–1200 K.

Creep behaviour of short fibre reinforced QE22 magnesium alloy using impression creep test

Creep properties of QE22 magnesium based alloy and composites reinforced with 20 volume percent of short-fibers - Maftech (R), Saffil (R) or Supertech (R), were evaluated using the impression creep test. In the impression creep test, a load is applied with the help of a cylindrical tungsten carbide indenter of 1 mm diameter. This has advantages over conventional creep testing in terms of small specimen size requirement and simple machining. Depth of impression is recorded with time and steady state strain rate is obtained from the slope of the secondary strain (depth of impression divided by indenter diameter) vs. time plot. The results are compared with the creep obtained from conventional creep performed in tension on the same materials earlier. Microstructural examination of the plastically deformed regions is carried out to explain creep behaviour of these composites.

Creep behaviour of Fe3Al-based alloys in DO3 phase field

A study is made to bring out the effect of alloying with Cr, Ti or Mn on the creep behaviour of Fe3Al. Impression creep experiments have been carried out in the DO3 phase field. In all the alloys, power law creep behaviour is observed in the stress range covered. The stress exponent for steady state creep rate and the activation energy for creep indicate that the creep rate is controlled by the dislocation climb process. Among the alloying elements studied, addition of Ti is most effective in improving the creep resistance.

Some mechanisms of tribofilm formation in metal/metal and ceramic/metal sliding interactions

Tribological interaction often generates new structures and materials which form the interface between the sliding pair. The new material designated tribofilm here may be protective or tribologically deleterious. The tribofilm plays a major role in determining the friction and wear of the interaction. Here, we give three examples: mechanically mixed, chemically generated and thermally activated, of tribofilms formed in three different tribological systems and speculate on the mechanism of their formation.

Synthesis of one-dimensional N-doped Ga2O3 nanostructures: different morphologies and different mechanisms

N-doped monoclinic Ga2O3 nanostructures of different morphologies have been synthesized by heating Ga metal in ambient air at 1150 degrees C to 1350 degrees C for 1 to 5 h duration. Neither catalyst nor any gas flow has been used for the synthesis of N-doped Ga2O3 nanostructures. The morphology was controlled by monitoring the curvature of the Ga droplet. Plausible growth mechanisms are discussed to explain the different morphology of the nanostructures. Elemental mapping by electron energy loss spectroscopy of the nanostructures indicate uniform distribution of Ga, O and N. It is interesting to note that we have used neither nitride source nor any gas flow but the synthesis was carried out in ambient air. We believe that ambient nitrogen acts as the source of nitrogen. Unintentional nitrogen doping of the Ga2O3 nanostructures is a straightforward method and such nanostructures could be promising candidates for white light emission.

Distinct mechanisms of DNA repair in mycobacteria and their implications in attenuation of the pathogen growth

About a third of the human population is estimated to be infected with Mycobacterium tuberculosis. Emergence of drug resistant strains and the protracted treatment strategies have compelled the scientific community to identify newer drug targets, and to develop newer vaccines. In the host macrophages, the bacterium survives within an environment rich in reactive nitrogen and oxygen species capable of damaging its genome. Therefore, for its successful persistence in the host, the pathogen must need robust DNA repair mechanisms. Analysis of M. tuberculosis genome sequence revealed that it lacks mismatch repair pathway suggesting a greater role for other DNA repair pathways such as the nucleotide excision repair, and base excision repair pathways. In this article, we summarize the outcome of research involving these two repair pathways in mycobacteria focusing primarily on our own efforts. Our findings, using Mycobacterium smegmatis model, suggest that deficiency of various DNA repair functions in single or in combinations severely compromises their DNA repair capacity and attenuates their growth under conditions typically encountered in macrophages. (C) 2011 Elsevier Ireland Ltd. All rights reserved.