Allostery and conformational free energy changes in human tryptophanyl-tRNA synthetase from essential dynamics and structure networks

The interdependence of the concept of allostery and enzymatic catalysis, and they being guided by conformational mobility is gaining increased prominence. However, to gain a molecular level understanding of llostery and hence of enzymatic catalysis, it is of utter importance that the networks of amino acids participating in allostery be deciphered. Our lab has been exploring the methods of network analysis combined with molecular dynamics simulations to understand allostery at molecular level. Earlier we had outlined methods to obtain communication paths and then to map the rigid/flexible regions of proteins through network parameters like the shortest correlated paths, cliques, and communities. In this article, we advance the methodology to estimate the conformational populations in terms of cliques/communities formed by interactions including the side-chains and then to compute the ligand-induced population shift. Finally, we obtain the free-energy landscape of the protein in equilibrium, characterizing the free-energy minima accessed by the protein complexes. We have chosen human tryptophanyl-tRNA synthetase (hTrpRS), a protein esponsible for charging tryptophan to its cognate tRNA during protein biosynthesis for this investigation. This is a multidomain protein exhibiting excellent allosteric communication. Our approach has provided valuable structural as well as functional insights into the protein. The methodology adopted here is highly generalized to illuminate the linkage between protein structure networks and conformational mobility involved in the allosteric mechanism in any protein with known structure.

Detection of microorganisms using biosensors-a smarter way towards detection techniques.

Along with useful microorganisms, there are some that cause potential damage to the animals and plants. Detection and identification of these harmful organisms in a cost and time effective way is a challenge for the researchers. The future of detection methods for microorganisms shall be guided by biosensor, which has already contributed enormously in sensing and detection technology. Here, we aim to review the use of various biosensors, developed by integrating the biological and physicochemical/mechanical properties (of tranducers), which can have enormous implication in healthcare, food, agriculture and biodefence. We have also highlighted the ways to improve the functioning of the biosensor.

Analysis of DNA sequence transformations on grids

Study of the evolution of species or organisms is essential for various biological applications. Evolution is typically studied at the molecular level by analyzing the mutations of DNA sequences of organisms. Techniques have been developed for building phylogenetic or evolutionary trees for a set of sequences. Though phylogenetic trees capture the overall evolutionary relationships among the sequences, they do not reveal fine-level details of the evolution. In this work, we attempt to resolve various fine-level sequence transformation details associated with a phylogenetic tree using cellular automata. In particular, our work tries to determine the cellular automata rules for neighbor-dependent mutations of segments of DNA sequences. We also determine the number of time steps needed for evolution of a progeny from an ancestor and the unknown segments of the intermediate sequences in the phylogenetic tree. Due to the existence of vast number of cellular automata rules, we have developed a grid system that performs parallel guided explorations of the rules on grid resources. We demonstrate our techniques by conducting experiments on a grid comprising machines in three countries and obtaining potentially useful statistics regarding evolutions in three HIV sequences. In particular, our work is able to verify the phenomenon of neighbor-dependent mutations and find that certain combinations of neighbor-dependent mutations, defined by a cellular automata rule, occur with greater than 90% probability. We also find the average number of time steps for mutations for some branches of phylogenetic tree over a large number of possible transformations with standard deviations less than 2.

A Compact Defected Ground Microstrip Device with Photonic Bandgap Effects

Filters and other devices using photonic bandgap (PBG) theory are typically implemented in microstrip lines by etching periodic holes on the ground plane of the microstrip. The period of such several holes corresponds to nearly half the guided wavelength of the transmission line. In this paper we study the effects of miniaturization of the PBG device by meandering the microstrip line about one single hole in the ground plane. A comparison of the S-parameters and dispersion behavior of the modified geometry and a conventional PBG device with a straight microstrip line shows that these devices have similar behaviors.

Role of information and communication in redefining unmanned aerial vehicle autonomous control levels

Autonomous mission control, unlike automatic mission control which is generally pre-programmed to execute an intended mission, is guided by the philosophy of carrying out a complete mission on its own through online sensing, information processing, and control reconfiguration. A crucial cornerstone of this philosophy is the capability of intelligence and of information sharing between unmanned aerial vehicles (UAVs) or with a central controller through secured communication links. Though several mission control algorithms, for single and multiple UAVs, have been discussed in the literature, they lack a clear definition of the various autonomous mission control levels. In the conventional system, the ground pilot issues the flight and mission control command to a UAV through a command data link and the UAV transmits intelligence information, back to the ground pilot through a communication link. Thus, the success of the mission depends entirely on the information flow through a secured communication link between ground pilot and the UAV In the past, mission success depended on the continuous interaction of ground pilot with a single UAV, while present day applications are attempting to define mission success through efficient interaction of ground pilot with multiple UAVs. However, the current trend in UAV applications is expected to lead to a futuristic scenario where mission success would depend only on interaction among UAV groups with no interaction with any ground entity. However, to reach this capability level, it is necessary to first understand the various levels of autonomy and the crucial role that information and communication plays in making these autonomy levels possible. This article presents a detailed framework of UAV autonomous mission control levels in the context of information flow and communication between UAVs and UAV groups for each level of autonomy.

In vitro antioxidant and in vivo prophylactic effects of two gamma-lactones isolated from Grewia tiliaefolia against hepatotoxicity in carbon tetrachloride intoxicated rats

Grewia tiliaefolia is widely used in traditional Indian medicines to cure jaundice, biliousness, dysentery and the diseases of blood. Bioassay-guided fractionation of methanolic extract of the G. tiliaefolia bark has resulted in the isolation of D-erythro-2-hexenoic acid gamma-lactone (EHGL) and gulonic acid gamma-lactone (GAGL). Hepatoprotective activity of the methanolic extract and the isolated constituents were evaluated against CCl4-induced hepatotoxicity in rats. The treatment with methanolic extract, EHGL and GAGL at oral doses of 100, 150 and 60 mg/kg respectively with concomitant CCl4 intraperitoneal injection (I ml/kg) significantly reduced the elevated plasma levels of aminotransferases, alkaline phosphatase and the incidence of liver necrosis compared with the CCl4-injected group without affecting the concentrations of serum bilirubin and hepatic markers. EHGL and GAGL significantly inhibited the elevated levels of thiobarbituric acid reactive substances and glutathione in liver homogenates. Histology of the liver tissues of the extract and isolated constituents treated groups showed the presence of normal hepatic cords, absence of necrosis and fatty infiltration as similar to the normal control. The results revealed that the hepatoprotective activity of EHGL is significant as similar to the standard drug silymarin. To clarify the influence of the extract and isolated constituents on the protection of oxidative-hepatic damage, we examined in vitro antioxidant properties of the test compounds. The extract and the constituents showed significant free radical scavenging activity. These results suggest that the extract as well as the constituents could protect the hepatocytes from CCl4-induced liver damage perhaps, by their anti-oxidative effect on hepatocytes, hence eliminating the deleterious effects of toxic metabolites from CCl4, (C) 2009 Elsevier B.V. All rights reserved.

Using a structural approach to identify relationships between soil and erosion in a semi-humid forested area, South India

Biogeochemical and hydrological cycles are currently studied on a small experimental forested watershed (4.5 km(2)) in the semi-humid South India. This paper presents one of the first data referring to the distribution and dynamics of a widespread red soil (Ferralsols and Chromic Luvisols) and black soil (Vertisols and Vertic intergrades) cover, and its possible relationship with the recent development of the erosion process. The soil map was established from the observation of isolated soil profiles and toposequences, and surveys of soil electromagnetic conductivity (EM31, Geonics Ltd), lithology and vegetation. The distribution of the different parts of the soil cover in relation to each other was used to establish the dynamics and chronological order of formation. Results indicate that both topography and lithology (gneiss and amphibolite) have influenced the distribution of the soils. At the downslope, the following parts of the soil covers were distinguished: i) red soil system, ii) black soil system, iii) bleached horizon at the top of the black soil and iv) bleached sandy saprolite at the base of the black soil. The red soil is currently transforming into black soil and the transformation front is moving upslope. In the bottom part of the slope, the chronology appears to be the following: black soil > bleached horizon at the top of the black soil > streambed > bleached horizon below the black soil. It appears that the development of the drainage network is a recent process, which was guided by the presence of thin black soil with a vertic horizon less than 2 in deep. Three distinctive types of erosional landforms have been identified: 1. rotational slips (Type 1); 2. a seepage erosion (Type 2) at the top of the black soil profile; 3. A combination of earthflow and sliding in the non-cohesive saprolite of the gneiss occurs at midslope (Type 3). Types 1 and 2 erosion are mainly occurring downslope and are always located at the intersection between the streambed and the red soil-black soil contact. Neutron probe monitoring, along an area vulnerable to erosion types 1 and 2, indicates that rotational slips are caused by a temporary watertable at the base of the black soil and within the sandy bleached saprolite, which behaves as a plane of weakness. The watertable is induced by the ephemeral watercourse. Erosion type 2 is caused by seepage of a perched watertable, which occurs after swelling and closing of the cracks of the vertic clay horizon and within a light textured and bleached horizon at the top of black soil. Type 3 erosion is not related to the red soil-black soil system but is caused by the seasonal seepage of saturated throughflow in the sandy saprolite of the gneiss occurring at midslope. (c) 2006 Elsevier B.V. All rights reserved.

Construction and use of linear regression models for processor performance analysis

Processor architects have a challenging task of evaluating a large design space consisting of several interacting parameters and optimizations. In order to assist architects in making crucial design decisions, we build linear regression models that relate Processor performance to micro-architecture parameters, using simulation based experiments. We obtain good approximate models using an iterative process in which Akaike's information criteria is used to extract a good linear model from a small set of simulations, and limited further simulation is guided by the model using D-optimal experimental designs. The iterative process is repeated until desired error bounds are achieved. We used this procedure to establish the relationship of the CPI performance response to 26 key micro-architectural parameters using a detailed cycle-by-cycle superscalar processor simulator The resulting models provide a significance ordering on all micro-architectural parameters and their interactions, and explain the performance variations of micro-architectural techniques.

Antibacterial & antiplasmid activities of Helicteres isora L.

Background & objectives: The multiple drug resistance (MDR) is a serious health problem and major challenge to the global drug discovery programmes. Most of the genetic determinants that confer resistance to antibiotics are located on R-plasmids in bacteria. The present investigation was undertaken to investigate the ability of organic extract of the fruits of Helicteres isora to cure R-plasmids from certain clinical isolates. mMethods: Active fractions demonstrating antibacterial and antiplasmid activities were isolated from the acetone extracts of shade dried fruits of H. isora by bioassay guided fractionation. Minimal inhibitory concentration (MIC) of antibiotics and organic extracts was determined by agar dilution method. Plasmid curing activity of organic fractions was determined by evaluating the ability of bacterial colonies (pre treated with organic fraction for 18 h) to grow in the presence of antibiotics. The physical loss of plasmid DNA in the cured derivatives was further confirmed by agarose gel electrophoresis. Results: The active fraction did not inhibit the growth of either the clinical isolates or the strains harbouring reference plasmids even at a concentration of 400 mu g/ml. However, the same fraction could cure plasmids from Enterococcus faecalis, Escherichia coli, Bacillus cereus and E. coli (RP4) at curing efficiencies of 14, 26, 22 and 2 per cent respectively. The active fraction mediated plasmid curing resulted in the subsequent loss of antibiotic resistance encoded in the plasmids as revealed by antibiotic resistance profile of cured strains. The physical loss of plasmid was also confirmed by agarose gel electrophoresis. Interpretation & conclusions: The active fraction of acetone extract of H. isora fruits cured R-plasmids from Gram-positive and Gram-negative clinical isolates as well as reference strains. Such plasmid loss reversed the multiple antibiotic resistance in cured derivatives making them sensitive to low concentrations of antibiotics. Acetone fractions of H. isora may be a source to develop antiplasmid agents of natural origin to contain the development and spread of plasmid borne multiple antibiotic resistance.