Deorphanization of Malonyl CoA:ACP Transacylase Drug Target in Plasmodium falciparum (PfFabD) Using Bacterial Antagonists: A Piggyback' Approach for Antimalarial Drug Discovery

Quest for new drug targets in Plasmodium sp. has underscored malonyl CoA:ACP transacylase (PfFabD) of fatty acid biosynthetic pathway in apicoplast. In this study, a piggyback approach was employed for the receptor deorphanization using inhibitors of bacterial FabD enzymes. Due to the lack of crystal structure, theoretical model was constructed using the structural details of homologous enzymes. Sequence and structure analysis has localized the presence of two conserved pentapeptide motifs: GQGXG and GXSXG and five key invariant residues viz., Gln109, Ser193, Arg218, His305 and Gln354 characteristic of FabD enzyme. Active site mapping of PfFabD using substrate molecules has disclosed the spatial arrangement of key residues in the cavity. As structurally similar molecules exhibit similar biological activities, signature pharmacophore fingerprints of FabD antagonists were generated using 0D-3D descriptors for molecular similarity-based cluster analysis and to correlate with their binding profiles. It was observed that antagonists showing good geometrical fitness score were grouped in cluster-1, whereas those exhibiting high binding affinities in cluster-2. This study proves important to shed light on the active site environment to reveal the hotspot for binding with higher affinity and to narrow down the virtual screening process by searching for close neighbors of the active compounds.

Low cost calibrated mechanical noisemaker for hearing screening of neonates in resource constrained settings

Background & objectives: There is a need to develop an affordable and reliable tool for hearing screening of neonates in resource constrained, medically underserved areas of developing nations. This study valuates a strategy of health worker based screening of neonates using a low cost mechanical calibrated noisemaker followed up with parental monitoring of age appropriate auditory milestones for detecting severe-profound hearing impairment in infants by 6 months of age. Methods: A trained health worker under the supervision of a qualified audiologist screened 425 neonates of whom 20 had confirmed severe-profound hearing impairment. Mechanical calibrated noisemakers of 50, 60, 70 and 80 dB (A) were used to elicit the behavioural responses. The parents of screened neonates were instructed to monitor the normal language and auditory milestones till 6 months of age. This strategy was validated against the reference standard consisting of a battery of tests - namely, auditory brain stem response (ABR), otoacoustic emissions (OAE) and behavioural assessment at 2 years of age. Bayesian prevalence weighted measures of screening were calculated. Results: The sensitivity and specificity was high with least false positive referrals for. 70 and 80 dB (A) noisemakers. All the noisemakers had 100 per cent negative predictive value. 70 and 80 dB (A) noisemakers had high positive likelihood ratios of 19 and 34, respectively. The probability differences for pre- and post- test positive was 43 and 58 for 70 and 80 dB (A) noisemakers, respectively. Interpretation & conclusions: In a controlled setting, health workers with primary education can be trained to use a mechanical calibrated noisemaker made of locally available material to reliably screen for severe-profound hearing loss in neonates. The monitoring of auditory responses could be done by informed parents. Multi-centre field trials of this strategy need to be carried out to examine the feasibility of community health care workers using it in resource constrained settings of developing nations to implement an effective national neonatal hearing screening programme.

Mixed-ligand aroylhydrazone complexes of molybdenum: Synthesis, structure and biological activity

The reaction of the benzoylhydrazone of 2-hydroxybenzaldehyde (H2L) with MoO2(acac)(2)] proceeds smoothly in refluxing ethanol to afford an orange complex MoO2L(C2H5OH)] (1). The substrate binding capacity of 1 has been demonstrated by the formation and isolation of two mononuclear MoO2L(Q)] {where Q = imidazole (2a) and 1-methylimidazole (2b)} and one dinuclear (MoO2L)(2)(Q)] {Q = 4,4'-bipyridine (3)} mixed-ligand oxomolybdenum complex. All the complexes have been characterized by elemental analysis, magnetic and spectroscopic (IR, UV-Vis and NMR) measurements. The molecular structures of all the oxomolybdenum(VI) complexes (1, 2a, 2b and 3) have been determined by X-ray crystallography. In each complex, the dianionic planar ligand is coordinated to the metal centre via one enolate oxygen, one phenolate oxygen and an azomethine nitrogen atom. The complexes have been screened for their antibacterial activity against Escherichia coli, Bacillus and Pseudomonas aeruginosa. The minimum inhibitory concentration of these complexes and their antibacterial activity indicates that compounds 2a and 2b are potential lead molecules for drug designing. (C) 2012 Elsevier Ltd. All rights reserved.

Quantum corrections to screening at strong coupling

We compute a certain class of corrections to (specific) screening lengths in strongly coupled non-abelian plasmas using the AdS/CFT correspondence. In this holographic framework, these corrections arise from various higher curvature interactions modifying the leading Einstein gravity action. The changes in the screening lengths are perturbative in inverse powers of the `t Hooft coupling or of the number of colors, as can be made precise in the context where the dual gauge theory is superconformal. We also compare the results of these holographic calculations to lattice results for the analogous screening lengths in QCD. In particular, we apply these results within the program of making quantitative comparisons between the strongly coupled quark-gluon plasma and holographic descriptions of conformal field theory. (c) 2012 Elsevier B.V. All rights reserved.

Computational algorithms inspired by biological processes and evolution

In recent times computational algorithms inspired by biological processes and evolution are gaining much popularity for solving science and engineering problems. These algorithms are broadly classified into evolutionary computation and swarm intelligence algorithms, which are derived based on the analogy of natural evolution and biological activities. These include genetic algorithms, genetic programming, differential evolution, particle swarm optimization, ant colony optimization, artificial neural networks, etc. The algorithms being random-search techniques, use some heuristics to guide the search towards optimal solution and speed-up the convergence to obtain the global optimal solutions. The bio-inspired methods have several attractive features and advantages compared to conventional optimization solvers. They also facilitate the advantage of simulation and optimization environment simultaneously to solve hard-to-define (in simple expressions), real-world problems. These biologically inspired methods have provided novel ways of problem-solving for practical problems in traffic routing, networking, games, industry, robotics, economics, mechanical, chemical, electrical, civil, water resources and others fields. This article discusses the key features and development of bio-inspired computational algorithms, and their scope for application in science and engineering fields.

Analytical solutions for diffuse fluorescence spectroscopy/imaging in biological tissues. Part I: zero and extrapolated boundary conditions

The mathematical model for diffuse fluorescence spectroscopy/imaging is represented by coupled partial differential equations (PDEs), which describe the excitation and emission light propagation in soft biological tissues. The generic closed-form solutions for these coupled PDEs are derived in this work for the case of regular geometries using the Green's function approach using both zero and extrapolated boundary conditions. The specific solutions along with the typical data types, such as integrated intensity and the mean time of flight, for various regular geometries were also derived for both time-and frequency-domain cases. (C) 2013 Optical Society of America

Analytical solutions for diffuse fluorescence spectroscopy/imaging in biological tissues. Part II: comparison and validation

The analytical solutions for the coupled diffusion equations that are encountered in diffuse fluorescence spectroscopy/ imaging for regular geometries were compared with the well-established numerical models, which are based on the finite element method. Comparison among the analytical solutions obtained using zero boundary conditions and extrapolated boundary conditions (EBCs) was also performed. The results reveal that the analytical solutions are in close agreement with the numerical solutions, and solutions obtained using EBCs are more accurate in obtaining the mean time of flight data compared to their counterpart. The analytical solutions were also shown to be capable of providing bulk optical properties through a numerical experiment using a realistic breast model. (C) 2013 Optical Society of America

Mixed-ligand nickel(II) thiosemicarbazone complexes: Synthesis, characterization and biological evaluation

The syntheses and characterization of some new mixed-ligand nickel(II) complexes {Ni(L-1)(PPh3)] (1), Ni(L-1)(Py)] (2), Ni(L-2)(PPh3)]center dot DMSO (3), Ni(L-2)(Imz)] (4), Ni(L-3)(4-pic)] (5) and RNi(L-3))(2)(mu-4,4'-byp)]center dot 2DMSO (6)1 of three selected thiosemicarbazones the 4-(p-X-phenyl)thiosemicarbazones of salicylaldehyde) (H2L1-3) (A, Scheme 1) are described in the present study, differing in the inductive effect of the substituent X (X = F, Br and OCH3), in order to observe its influence, if any, on the redox potentials and biological activity of the complexes. All the synthesized ligands and the metal complexes were successfully characterized by elemental analysis, IR, UV-Vis, NMR spectroscopy and cyclic voltammetry. The molecular structures of four mononuclear (1-3 and 5) and one dinuclear (6) Ni(II) complex have been determined by X-ray crystallography. The complexes have been screened for their antibacterial activity against Escherichia coli and Bacillus. The minimum inhibitory concentrations of these complexes and their antibacterial activities indicate that compound 4 is the potential lead molecule for drug designing. (C) 2012 Elsevier Ltd. All rights reserved.

A study on the usefulness of Support Vector Machines for the realtime computational simulation of soft biological organs

Realistic and realtime computational simulation of soft biological organs (e.g., liver, kidney) is necessary when one tries to build a quality surgical simulator that can simulate surgical procedures involving these organs. Since the realistic simulation of these soft biological organs should account for both nonlinear material behavior and large deformation, achieving realistic simulations in realtime using continuum mechanics based numerical techniques necessitates the use of a supercomputer or a high end computer cluster which are costly. Hence there is a need to employ soft computing techniques like Support Vector Machines (SVMs) which can do function approximation, and hence could achieve physically realistic simulations in realtime by making use of just a desktop computer. Present work tries to simulate a pig liver in realtime. Liver is assumed to be homogeneous, isotropic, and hyperelastic. Hyperelastic material constants are taken from the literature. An SVM is employed to achieve realistic simulations in realtime, using just a desktop computer. The code for the SVM is obtained from [1]. The SVM is trained using the dataset generated by performing hyperelastic analyses on the liver geometry, using the commercial finite element software package ANSYS. The methodology followed in the present work closely follows the one followed in [2] except that [2] uses Artificial Neural Networks (ANNs) while the present work uses SVMs to achieve realistic simulations in realtime. Results indicate the speed and accuracy that is obtained by employing the SVM for the targeted realistic and realtime simulation of the liver.

A study of the speed and the accuracy of the Boundary Element Method as applied to the computational simulation of biological organs

In this work, first a Fortran code is developed for three dimensional linear elastostatics using constant boundary elements; the code is based on a MATLAB code developed by the author earlier. Next, the code is parallelized using BLACS, MPI, and ScaLAPACK. Later, the parallelized code is used to demonstrate the usefulness of the Boundary Element Method (BEM) as applied to the realtime computational simulation of biological organs, while focusing on the speed and accuracy offered by BEM. A computer cluster is used in this part of the work. The commercial software package ANSYS is used to obtain the `exact' solution against which the solution from BEM is compared; analytical solutions, wherever available, are also used to establish the accuracy of BEM. A pig liver is the biological organ considered. Next, instead of the computer cluster, a Graphics Processing Unit (GPU) is used as the parallel hardware. Results indicate that BEM is an interesting choice for the simulation of biological organs. Although the use of BEM for the simulation of biological organs is not new, the results presented in the present study are not found elsewhere in the literature. Also, a serial MATLAB code, and both serial and parallel versions of a Fortran code, which can solve three dimensional (3D) linear elastostatic problems using constant boundary elements, are provided as supplementary files that can be freely downloaded.

RepEx: Repeat extractor for biological sequences

Genomic sequences are far from being random but are made up of systematically ordered and information rich patterns. These repeated sequence patterns have been vastly utilized for their fundamental importance in understanding the genome function and organization. To this end, a comprehensive toolkit, RepEx, has been developed which extracts repeat (inverted, everted and mirror) patterns from the given genome sequence(s) without any constraints. The toolkit can also be used to fetch the inverted repeats present in the protein sequence (s). Further, it is capable of extracting exact and degenerate repeats with a user defined spacer intervals. It is remarkably more precise and sensitive when compared to the existing tools. An example with comprehensive case studies and a performance evaluation of the proposed toolkit has been presented to authenticate its efficiency and accuracy. (C) 2013 Elsevier Inc. All rights reserved.

Biological sulfate reduction of a sulfate-rich industrial waste liquor using sulfate reducing bacteria

An industrial waste liquor having high sulfate concentrations was subjected to biological treatment using the sulfate-reducing bacteria (SRB) Desulfovibrio desulfuricans. Toxicity levels of different sulfate, cobalt and nickel concentrations toward growth of the SRB with respect to biological sulfate reduction kinetics was initially established. Optimum sulfate concentration to promote SRB growth amounted to 0.8 - 1 g/L. The strain of D. desulfuricans used in this study initially tolerated up to 4 -5 g/L of sulfate or 50 mg/L of cobalt and nickel, while its tolerance could be further enhanced through adaptation by serial subculturing in the presence of increasing concentrations of sulfate, cobalt and nickel. From the waste liquor, more than 70% of sulfate and 95% of cobalt and nickel could be precipitated as sulfides, using a preadapted strain of D. desulfuricans. Probable mechanisms involving biological sulfide precipitation and metal adsorption onto precipitates and bacterial cells are discussed.

A study of the speed and the accuracy of the Boundary Element Method as applied to the computational simulation of biological organs

In this work, possibility of simulating biological organs in realtime using the Boundary Element Method (BEM) is investigated, with specific reference to the speed and the accuracy offered by BEM. First, a Graphics Processing Unit (GPU) is used to speed up the BEM computations to achieve the realtime performance. Next, instead of the GPU, a computer cluster is used. A pig liver is the biological organ considered. Results indicate that BEM is an interesting choice for the simulation of biological organs. Although the use of BEM for the simulation of biological organs is not new, the results presented in the present study are not found elsewhere in the literature.

A Study of Speed of the Boundary Element Method as applied to the Realtime Computational Simulation of Biological Organs

In this work, possibility of simulating biological organs in realtime using the Boundary Element Method (BEM) is investigated. Biological organs are assumed to follow linear elastostatic material behavior, and constant boundary element is the element type used. First, a Graphics Processing Unit (GPU) is used to speed up the BEM computations to achieve the realtime performance. Next, instead of the GPU, a computer cluster is used. Results indicate that BEM is fast enough to provide for realtime graphics if biological organs are assumed to follow linear elastostatic material behavior. Although the present work does not conduct any simulation using nonlinear material models, results from using the linear elastostatic material model imply that it would be difficult to obtain realtime performance if highly nonlinear material models that properly characterize biological organs are used. Although the use of BEM for the simulation of biological organs is not new, the results presented in the present study are not found elsewhere in the literature.

Group behaviour in physical, chemical and biological systems

Groups exhibit properties that either are not perceived to exist, or perhaps cannot exist, at the individual level. Such `emergent' properties depend on how individuals interact, both among themselves and with their surroundings. The world of everyday objects consists of material entities. These are, ultimately, groups of elementary particles that organize themselves into atoms and molecules, occupy space, and so on. It turns out that an explanation of even the most commonplace features of this world requires relativistic quantum field theory and the fact that Planck's constant is discrete, not zero. Groups of molecules in solution, in particular polymers ('sols'), can form viscous clusters that behave like elastic solids ('gels'). Sol-gel transitions are examples of cooperative phenomena. Their occurrence is explained by modelling the statistics of inter-unit interactions: the likelihood of either state varies sharply as a critical parameter crosses a threshold value. Group behaviour among cells or organisms is often heritable and therefore can evolve. This permits an additional, typically biological, explanation for it in terms of reproductive advantage, whether of the individual or of the group. There is no general agreement on the appropriate explanatory framework for understanding group-level phenomena in biology.