Surface chemical and adsorption studies using Thiobacillus ferrooxidans with reference to bacterial adhesion to sulfide minerals

Adhesion of Thiobacillus ferrooxidans to pyrite and chalcopyrite in relation to its importance in bioleaching and bioflotation has been studied. Electrokinetic studies as well as FT-IR spectra suggest that the surface chemistry of Thiobacillus ferrooxidans depends on bacterial growth conditions. Sulfur-,Pyrite- and chalcopyrite-grown Thiobacillus ferrooxidans were found to be relatively more hydrophobic. The altered surface chemistry of Thiobacillus ferrooxidans was due to secretion of newer and specific proteinaceous compounds. The adsorption density corresponds to a monolayer coverage in a horizontal orientation of the cells. The xanthate flotation of pyrite in presence of Thiobacillus ferrooxidans is strongly depressed where as the cells have insignificant effect on chalcopyrite flotation. This study demonstrate that: (a)Thiobacillus ferrooxidans cells can be used for selective flotation of chalcopyrite from pyrite and importantly at natural pH values. (b)Sulfur-grown cells exhibits higher leaching kinetics than ferrous ion-grown cells.

Features of a unique intronless cluster of class I small heat shock protein genes in tandem with box C/D snoRNA genes on chromosome 6 in tomato (Solanum lycopersicum)

Physical clustering of genes has been shown in plants; however, little is known about gene clusters that have different functions, particularly those expressed in the tomato fruit. A class I 17.6 small heat shock protein (Sl17.6 shsp) gene was cloned and used as a probe to screen a tomato (Solanum lycopersicum) genomic library. An 8.3-kb genomic fragment was isolated and its DNA sequence determined. Analysis of the genomic fragment identified intronless open reading frames of three class I shsp genes (Sl17.6, Sl20.0, and Sl20.1), the Sl17.6 gene flanked by Sl20.1 and Sl20.0, with complete 5' and 3' UTRs. Upstream of the Sl20.0 shsp, and within the shsp gene cluster, resides a box C/D snoRNA cluster made of SlsnoR12.1 and SlU24a. Characteristic C and D, and C' and D', boxes are conserved in SlsnoR12.1 and SlU24a while the upstream flanking region of SlsnoR12.1 carries TATA box 1, homol-E and homol-D box-like cis sequences, TM6 promoter, and an uncharacterized tomato EST. Molecular phylogenetic analysis revealed that this particular arrangement of shsps is conserved in tomato genome but is distinct from other species. The intronless genomic sequence is decorated with cis elements previously shown to be responsive to cues from plant hormones, dehydration, cold, heat, and MYC/MYB and WRKY71 transcription factors. Chromosomal mapping localized the tomato genomic sequence on the short arm of chromosome 6 in the introgression line (IL) 6-3. Quantitative polymerase chain reaction analysis of gene cluster members revealed differential expression during ripening of tomato fruit, and relatively different abundances in other plant parts.

Artificial neural network application to power system voltage stability improvement

As power systems grow in their size and interconnections, their complexity increases. Rising costs due to inflation and increased environmental concerns has made transmission, as well as generation systems be operated closer to design limits. Hence power system voltage stability and voltage control are emerging as major problems in the day-to-day operation of stressed power systems. For secure operation and control of power systems under normal and contingency conditions it is essential to provide solutions in real time to the operator in energy control center (ECC). Artificial neural networks (ANN) are emerging as an artificial intelligence tool, which give fast, though approximate, but acceptable solutions in real time as they mostly use the parallel processing technique for computation. The solutions thus obtained can be used as a guide by the operator in ECC for power system control. This paper deals with development of an ANN architecture, which provide solutions for monitoring, and control of voltage stability in the day-to-day operation of power systems.

Familial Diarrhea Syndrome Caused by an Activating GUCY2C Mutation

BACKGROUND Familial diarrhea disorders are, in most cases, severe and caused by recessive mutations. We describe the cause of a novel dominant disease in 32 members of a Norwegian family. The affected members have chronic diarrhea that is of early onset, is relatively mild, and is associated with increased susceptibility to inflammatory bowel disease, small-bowel obstruction, and esophagitis. METHODS We used linkage analysis, based on arrays with single-nucleotide polymorphisms, to identify a candidate region on chromosome 12 and then sequenced GUCY2C, encoding guanylate cyclase C (GC-C), an intestinal receptor for bacterial heat-stable enterotoxins. We performed exome sequencing of the entire candidate region from three affected family members, to exclude the possibility that mutations in genes other than GUCY2C could cause or contribute to susceptibility to the disease. We carried out functional studies of mutant GC-C using HEK293T cells. RESULTS We identified a heterozygous missense mutation (c.2519G -> T) in GUCY2C in all affected family members and observed no other rare variants in the exons of genes in the candidate region. Exposure of the mutant receptor to its ligands resulted in markedly increased production of cyclic guanosine monophosphate (cGMP). This may cause hyperactivation of the cystic fibrosis transmembrane regulator (CFTR), leading to increased chloride and water secretion from the enterocytes, and may thus explain the chronic diarrhea in the affected family members. CONCLUSIONS Increased GC-C signaling disturbs normal bowel function and appears to have a proinflammatory effect, either through increased chloride secretion or additional effects of elevated cellular cGMP. Further investigation of the relevance of genetic variants affecting the GC-C-CFTR pathway to conditions such as Crohn's disease is warranted. (Funded by Helse Vest Western Norway Regional Health Authority] and the Department of Science and Technology, Government of India.)

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.

Promiscuous restriction is a cellular defense strategy that confers fitness advantage to bacteria

Most bacterial genomes harbor restriction-modification systems, encoding a REase and its cognate MTase. On attack by a foreign DNA, the REase recognizes it as nonself and subjects it to restriction. Should REases be highly specific for targeting the invading foreign DNA? It is often considered to be the case. However, when bacteria harboring a promiscuous or high-fidelity variant of the REase were challenged with bacteriophages, fitness was maximal under conditions of catalytic promiscuity. We also delineate possible mechanisms by which the REase recognizes the chromosome as self at the noncanonical sites, thereby preventing lethal dsDNA breaks. This study provides a fundamental understanding of how bacteria exploit an existing defense system to gain fitness advantage during a host-parasite coevolutionary ``arms race.''

A Rhodanine Derivative CCR-11 Inhibits Bacterial Proliferation by Inhibiting the Assembly and GTPase Activity of FtsZ

A perturbation of FtsZ assembly dynamics has been shown to inhibit bacterial cytokinesis. In this study, the antibacterial activity of 151 rhodanine compounds was assayed using Bacillus subtilis cells. Of 151 compounds, eight strongly inhibited bacterial proliferation at 2 mu M. Subsequently, we used the elongation of B. subtilis cells as a secondary screen to identify potential FtsZ-targeted antibacterial agents. We found that three compounds significantly increased bacterial cell length. One of the three compounds, namely, CCR-11 (E)-2-thioxo-5-({3-(trifluoromethyl)phenyl]furan-2-yl}methylene) thiazolidin-4-one], inhibited the assembly and GTPase activity of FtsZ in vitro. CCR-11 bound to FtsZ with a dissociation constant of 1.5 +/- 0.3 mu M. A docking analysis indicated that CCR-11 may bind to FtsZ in a cavity adjacent to the T7 loop and that short halogen oxygen, H-bonding, and hydrophobic interactions might be important for the binding of CCR-11 with FtsZ. CCR-11 inhibited the proliferation of B. subtilis cells with a half-maximal inhibitory concentration (IC50) of 1.2 +/- 0.2 mu M and a minimal inhibitory concentration of 3 mu M. It also potently inhibited proliferation of Mycobacterium smegmatis cells. Further, CCR-11 perturbed Z-ring formation in B. subtilis cells; however, it neither visibly affected nucleoid segregation nor altered the membrane integrity of the cells. CCR-11 inhibited HeLa cell proliferation with an IC50 value of 18.1 +/- 0.2,mu M (similar to 15 x IC50 of B. subtilis cell proliferation). The results suggested that CCR-11 inhibits bacterial cytokinesis by inhibiting FtsZ assembly, and it can be used as a lead molecule to develop FtsZ-targeted antibacterial agents.

Cascaded walks in protein sequence space: use of artificial sequences in remote homology detection between natural proteins

Over the past two decades, many ingenious efforts have been made in protein remote homology detection. Because homologous proteins often diversify extensively in sequence, it is challenging to demonstrate such relatedness through entirely sequence-driven searches. Here, we describe a computational method for the generation of `protein-like' sequences that serves to bridge gaps in protein sequence space. Sequence profile information, as embodied in a position-specific scoring matrix of multiply aligned sequences of bona fide family members, serves as the starting point in this algorithm. The observed amino acid propensity and the selection of a random number dictate the selection of a residue for each position in the sequence. In a systematic manner, and by applying a `roulette-wheel' selection approach at each position, we generate parent family-like sequences and thus facilitate an enlargement of sequence space around the family. When generated for a large number of families, we demonstrate that they expand the utility of natural intermediately related sequences in linking distant proteins. In 91% of the assessed examples, inclusion of designed sequences improved fold coverage by 5-10% over searches made in their absence. Furthermore, with several examples from proteins adopting folds such as TIM, globin, lipocalin and others, we demonstrate that the success of including designed sequences in a database positively sensitized methods such as PSI-BLAST and Cascade PSI-BLAST and is a promising opportunity for enormously improved remote homology recognition using sequence information alone.

Stabilized SPH-based simulations of impact dynamics using acceleration-corrected artificial viscosity

Artificial viscosity in SPH-based computations of impact dynamics is a numerical artifice that helps stabilize spurious oscillations near the shock fronts and requires certain user-defined parameters. Improper choice of these parameters may lead to spurious entropy generation within the discretized system and make it over-dissipative. This is of particular concern in impact mechanics problems wherein the transient structural response may depend sensitively on the transfer of momentum and kinetic energy due to impact. In order to address this difficulty, an acceleration correction algorithm was proposed in Shaw and Reid (''Heuristic acceleration correction algorithm for use in SPH computations in impact mechanics'', Comput. Methods Appl. Mech. Engrg., 198, 3962-3974) and further rationalized in Shaw et al. (An Optimally Corrected Form of Acceleration Correction Algorithm within SPH-based Simulations of Solid Mechanics, submitted to Comput. Methods Appl. Mech. Engrg). It was shown that the acceleration correction algorithm removes spurious high frequency oscillations in the computed response whilst retaining the stabilizing characteristics of the artificial viscosity in the presence of shocks and layers with sharp gradients. In this paper, we aim at gathering further insights into the acceleration correction algorithm by further exploring its application to problems related to impact dynamics. The numerical evidence in this work thus establishes that, together with the acceleration correction algorithm, SPH can be used as an accurate and efficient tool in dynamic, inelastic structural mechanics. (C) 2011 Elsevier Ltd. All rights reserved.

Under-representation of intrinsic terminators across bacterial genomic islands: Rho as a principal regulator of xenogenic DNA expression

Two transcription termination mechanisms - intrinsic and Rho-dependent - have evolved in bacteria. The Rho factor occurs in most bacterial lineages, and has been hypothesized to play a global regulatory role. Genome-wide studies using microarray, 2D-gel electrophoresis and ChIP-chip provided evidence that Rho serves to silence transcription from horizontally acquired genes and prophages in Escherichia coli K-12, implicating the factor to be a part of the ``cellular immune mechanism'' protecting against deleterious phages and aberrant gene expression from acquired xenogenic DNA. We have investigated this model by adopting an alternate in silico approach and have extended the study to other species. Our analysis shows that several genomic islands across diverse phyla have under-representation of intrinsic terminators, similar to that experimentally observed in E. coli K-12. This implies that Rho-dependent termination is the predominant process operational in these islands and that silencing of foreign DNA is a conserved function of Rho. From the present analysis, it is evident that horizontally acquired islands have lost intrinsic terminators to facilitate Rho-dependent termination. These results underscore the importance of Rho as a conserved, genome-wide sentinel that regulates potentially toxic xenogenic DNA. (C) 2012 Elsevier B.V. All rights reserved.

Curcumin reduces the antimicrobial activity of ciprofloxacin against Salmonella Typhimurium and Salmonella Typhi

Typhoidal and non-typhoidal infection by Salmonella is a serious threat to human health. Ciprofloxacin is the last drug of choice to clear the infection. Ciprofloxacin, a gyrase inhibitor, kills bacteria by inducing chromosome fragmentation, SOS response and reactive oxygen species (ROS) in the bacterial cell. Curcumin, an active ingredient from turmeric, is a major dietary molecule among Asians and possesses medicinal properties. Our research aimed at investigating whether curcumin modulates the action of ciprofloxacin. We investigated the role of curcumin in interfering with the antibacterial action of ciprofloxacin in vitro and in vivo. RTPCR, DNA fragmentation and confocal microscopy were used to investigate the modulation of ciprofloxacin-induced SOS response, DNA damage and subsequent filamentation by curcumin. Chemiluminescence and nitroblue tetrazolium reduction assays were performed to assess the interference of curcumin with ciprofloxacin-induced ROS. DNA binding and cleavage assays were done to understand the rescue of ciprofloxacin-mediated gyrase inhibition by curcumin. Curcumin interferes with the action of ciprofloxacin thereby increasing the proliferation of Salmonella Typhi and Salmonella Typhimurium in macrophages. In a murine model of typhoid fever, mice fed with curcumin had an increased bacterial burden in the reticuloendothelial system and succumbed to death faster. This was brought about by the inhibition of ciprofloxacin-mediated downstream signalling by curcumin. The antioxidant property of curcumin is crucial in protecting Salmonella against the oxidative burst induced by ciprofloxacin or interferon (IFN), a pro-inflammatory cytokine. However, curcumin is unable to rescue ciprofloxacin-induced gyrase inhibition. Curcumins ability to hinder the bactericidal action of ciprofloxacin and IFN might significantly augment Salmonella pathogenesis.

Prediction of Ground Water Levels in the Uplands of a Tropical Coastal Riparian Wetland using Artificial Neural Networks

Artificial Neural Networks (ANNs) have been found to be a robust tool to model many non-linear hydrological processes. The present study aims at evaluating the performance of ANN in simulating and predicting ground water levels in the uplands of a tropical coastal riparian wetland. The study involves comparison of two network architectures, Feed Forward Neural Network (FFNN) and Recurrent Neural Network (RNN) trained under five algorithms namely Levenberg Marquardt algorithm, Resilient Back propagation algorithm, BFGS Quasi Newton algorithm, Scaled Conjugate Gradient algorithm, and Fletcher Reeves Conjugate Gradient algorithm by simulating the water levels in a well in the study area. The study is analyzed in two cases-one with four inputs to the networks and two with eight inputs to the networks. The two networks-five algorithms in both the cases are compared to determine the best performing combination that could simulate and predict the process satisfactorily. Ad Hoc (Trial and Error) method is followed in optimizing network structure in all cases. On the whole, it is noticed from the results that the Artificial Neural Networks have simulated and predicted the water levels in the well with fair accuracy. This is evident from low values of Normalized Root Mean Square Error and Relative Root Mean Square Error and high values of Nash-Sutcliffe Efficiency Index and Correlation Coefficient (which are taken as the performance measures to calibrate the networks) calculated after the analysis. On comparison of ground water levels predicted with those at the observation well, FFNN trained with Fletcher Reeves Conjugate Gradient algorithm taken four inputs has outperformed all other combinations.

Application of Artificial Neural Networks and Particle Swarm Optimization for the Management of Groundwater Resources

Ground management problems are typically solved by the simulation-optimization approach where complex numerical models are used to simulate the groundwater flow and/or contamination transport. These numerical models take a lot of time to solve the management problems and hence become computationally expensive. In this study, Artificial Neural Network (ANN) and Particle Swarm Optimization (PSO) models were developed and coupled for the management of groundwater of Dore river basin in France. The Analytic Element Method (AEM) based flow model was developed and used to generate the dataset for the training and testing of the ANN model. This developed ANN-PSO model was applied to minimize the pumping cost of the wells, including cost of the pipe line. The discharge and location of the pumping wells were taken as the decision variable and the ANN-PSO model was applied to find out the optimal location of the wells. The results of the ANN-PSO model are found similar to the results obtained by AEM-PSO model. The results show that the ANN model can reduce the computational burden significantly as it is able to analyze different scenarios, and the ANN-PSO model is capable of identifying the optimal location of wells efficiently.