DNA Binding, Coprotease, and Strand Exchange Activities of Mycobacterial RecA Proteins: Implications for Functional Diversity among RecA Nucleoprotein Filaments

One of the fundamental questions concerning homologous recombination is how RecA or its homologues recognize several DNA sequences with high affinity and catalyze all the diverse biological activities. In this study, we show that the extent of single-stranded DNA binding and strand exchange (SE) promoted by mycobacterial RecA proteins with DNA substrates having various degrees of GC content was comparable with that observed for Escherichia coli RecA. However, the rate and extent of SE promoted by these recombinases showed a strong negative correlation with increasing amounts of sequence divergence embedded at random across the length of the donor strand. Conversely, a positive correlation was seen between SE efficiency and the degree of sequence divergence in the recipient duplex DNA. The extent of heteroduplex formation was not significantly affected when both the pairing partners contained various degrees of sequence divergence, although there was a moderate decrease in the case of mycobacterial RecA proteins with substrates containing larger amounts of sequence divergence. Whereas a high GC content had no discernible effect on E. coli RecA coprotease activity, a negative correlation was apparent between mycobacterial RecA proteins and GC content. We further show clear differences in the extent of SE promoted by E. coli and mycobacterial RecA proteins in the presence of a wide range of ATP:ADP ratios. Taken together, our findings disclose the existence of functional diversity among E. coli and mycobacterial RecA nucleoprotein filaments, and the milieu of sequence divergence (i.e., in the donor or recipient) exerts differential effects on heteroduplex formation, which has implications for the emergence of new genetic variants.

Metallo-beta-lactamase and phosphotriesterase activities of some zinc(II) complexes

Metallo-beta-lactamases (m beta l) and phosphotriesterase (PTE) are zinc(II) enzymes, which hydrolyze the beta-lactam antibiotics and toxic organophosphotriesters, respectively. In the present work, we have synthesized a few asymmetric phenolate-based ligands by sequential Mannich reaction and their corresponding zinc(II) complexes. These zinc(II) complexes were studied for their m beta l and PTE activities. It is shown that the zinc(II) complexes can hydrolyze oxacillin, the beta-lactam antibiotic, at much higher rates as compared to the hydrolysis of p-nitrophenyl diphenylphosphate (PNPDPP), the phosphotriester. Among the complexes studied, the binuclear asymmetric complex 1 having a water molecule coordinated to one of the zinc(II) ions exhibits much better mbl activity than the mononuclear complexes. However, the mononuclear zinc(II) complexes having labile chloride ions exhibit significant PTE activity, which can be ascribed to the replacement of chloride ions by hydroxide ions during hydrolysis reactions. (C) 2011 Elsevier B.V. All rights reserved.

Multivariate nonlinear ensemble prediction of daily chaotic rainfall with climate inputs

The basic characteristic of a chaotic system is its sensitivity to the infinitesimal changes in its initial conditions. A limit to predictability in chaotic system arises mainly due to this sensitivity and also due to the ineffectiveness of the model to reveal the underlying dynamics of the system. In the present study, an attempt is made to quantify these uncertainties involved and thereby improve the predictability by adopting a multivariate nonlinear ensemble prediction. Daily rainfall data of Malaprabha basin, India for the period 1955-2000 is used for the study. It is found to exhibit a low dimensional chaotic nature with the dimension varying from 5 to 7. A multivariate phase space is generated, considering a climate data set of 16 variables. The chaotic nature of each of these variables is confirmed using false nearest neighbor method. The redundancy, if any, of this atmospheric data set is further removed by employing principal component analysis (PCA) method and thereby reducing it to eight principal components (PCs). This multivariate series (rainfall along with eight PCs) is found to exhibit a low dimensional chaotic nature with dimension 10. Nonlinear prediction employing local approximation method is done using univariate series (rainfall alone) and multivariate series for different combinations of embedding dimensions and delay times. The uncertainty in initial conditions is thus addressed by reconstructing the phase space using different combinations of parameters. The ensembles generated from multivariate predictions are found to be better than those from univariate predictions. The uncertainty in predictions is decreased or in other words predictability is increased by adopting multivariate nonlinear ensemble prediction. The restriction on predictability of a chaotic series can thus be altered by quantifying the uncertainty in the initial conditions and also by including other possible variables, which may influence the system. (C) 2011 Elsevier B.V. All rights reserved.

Activities of oxygen and lead in Pb-Ag O solutions

The reversible e.m.f. of galvanic cells: stainlesssteel,Ir,Pb+PbO|CaO+ZrO2|Ag+Pb+PbO,Ir,stainlesssteel,I and Pt,Ni+NiO|CaO+ZrO2|O(Pb+Ag),Cermet,Pt,II incorporating solid oxide electrolytes were measured as a function of alloy composition. In lead-rich alloys, the temperature dependence of the e.m.f. of cell I was also investigated. Since the solubility of oxygen in the alloy is small, the relative partial molar properties of lead in the binary Ag + Pb system can be calculated from the e.m.f. of this cell. The Gibbs free energies obtained in this study are combined with selected calorimetric data to provide a complete thermodynamic discription of liquid Ag + Pb Alloys. The activity coefficient of oxygen in the whole range of Ag + Pb alloys at 1273 K have been obtained from the e.m.f. of cell II; and these are found to deviate positively from Alcock and Richardson's quasichemical equation when the average co-ordination number of all the atoms is assigned a value of 2.

Prediction of activities of oxygen in dilute quaternary solutions using binary data

Equations are developed for predicting the activity coefficients of oxygen dissolved in ternary liquid alloys. These are extensions of earlier treatments, and are based on a model in which each oxygen atom is assumed to make four bonds with neighboring metal atoms. It is also postulated that the strong oxygen-metal bonds distort the electronic configuration around the metal atoms bonded to oxygen, and that the quantitative reduction of the strength of bonds made by these atoms with all of the adjacent metal atoms is equivalent to a factor of approximately two. The predictions of the quasichemical equation which is derived agree satisfactorily with the partial molar free energies of oxygen in Ag-Cu-Sn solutions at 1200°C reported in literature. An extension of this treatment to multicomponent solutions is also indicated.

Activities of indium in solid solutions of Cu+In, Au+In and Cu+Au+In alloys

Thin foils of Cu, Au and Cu + Au alloys embedded in indium sesquioxide were equilibrated with controlled streams of CO-CO2 mixtures. The equilibrium concentrations of indium in the foils were determined by neutron activation analysis. The corresponding chemical potentials of indium were calculated from the standard free energies of formation of carbon monoxide, carbon dioxide, and indium oxide. It was found that the size difference between the solute and the solvent does not make significant contributions to the solute—solute interaction energy in the α-phase. The chemical potential of indium at one at.% concentration is 8.6 Kcals more negative in gold than in copper at 900°K. The variation of this chemical potential with alloy composition in Cu + Au system was in good agreement with Alcock and Richardson's quasichemical equation. The agreement is strengthened by the accurate knowledge of the co-ordination number in these substitutional solid solutions from X-ray diffraction studies.

Synthesis, antimicrobial and cytotoxic activities of sulfone linked bis heterocycles

A new class of sulfone linked bis heterocycles viz., pyrrolyl/pyrazolyl arylaminosulfonylmethyl 1,3,4-oxadiazoles, 1,3,4-thiadiazoles, and 1,2,4-triazoles were prepared and tested for antimicrobial activity and cytotoxicity. The chloro-substituted compounds 5c, 8c and 14c showed comparable antibacterial activity to chloramphenicol against Pseudomonasaeruginosa and compound 5c exhibited comparable antifungal activity to ketoconazole against Penicilliumchrysogenum. One of the compounds, vinylsulfonyl oxadiazole showed appreciably cytotoxic activity on A549 lung carcinoma cells with an IC50 at a concentration of 31.7 mu M. (C) 2012 Elsevier Masson SAS. All rights reserved.

Differential Activities of the Two Closely Related Withanolides, Withaferin A and Withanone: Bioinformatics and Experimental Evidences

Background and Purpose: Withanolides are naturally occurring chemical compounds. They are secondary metabolites produced via oxidation of steroids and structurally consist of a steroid-backbone bound to a lactone or its derivatives. They are known to protect plants against herbivores and have medicinal value including anti-inflammation, anti-cancer, adaptogenic and anti-oxidant effects. Withaferin A (Wi-A) and Withanone (Wi-N) are two structurally similar withanolides isolated from Withania somnifera, also known as Ashwagandha in Indian Ayurvedic medicine. Ashwagandha alcoholic leaf extract (i-Extract), rich in Wi-N, was shown to kill cancer cells selectively. Furthermore, the two closely related purified phytochemicals, Wi-A and Wi-N, showed differential activity in normal and cancer human cells in vitro and in vivo. We had earlier identified several genes involved in cytotoxicity of i-Extract in human cancer cells by loss-of-function assays using either siRNA or randomized ribozyme library. Methodology/Principal Findings: In the present study, we have employed bioinformatics tools on four genes, i.e., mortalin, p53, p21 and Nrf2, identified by loss-of-function screenings. We examined the docking efficacy of Wi-N and Wi-A to each of the four targets and found that the two closely related phytochemicals have differential binding properties to the selected cellular targets that can potentially instigate differential molecular effects. We validated these findings by undertaking parallel experiments on specific gene responses to either Wi-N or Wi-A in human normal and cancer cells. We demonstrate that Wi-A that binds strongly to the selected targets acts as a strong cytotoxic agent both for normal and cancer cells. Wi-N, on the other hand, has a weak binding to the targets; it showed milder cytotoxicity towards cancer cells and was safe for normal cells. The present molecular docking analyses and experimental evidence revealed important insights to the use of Wi-A and Wi-N for cancer treatment and development of new anti-cancer phytochemical cocktails.

Predictability and chaotic nature of daily streamflow

The predictability of a chaotic series is limited to a few future time steps due to its sensitivity to initial conditions and the exponential divergence of the trajectories. Over the years, streamflow has been considered as a stochastic system in many approaches. In this study, the chaotic nature of daily streamflow is investigated using autocorrelation function, Fourier spectrum, correlation dimension method (Grassberger-Procaccia algorithm) and false nearest neighbor method. Embedding dimensions of 6-7 obtained indicates the possible presence of low-dimensional chaotic behavior. The predictability of the system is estimated by calculating the system’s Lyapunov exponent. A positive maximum Lyapunov exponent of 0.167 indicates that the system is chaotic and unstable with a maximum predictability of only 6 days. These results give a positive indication towards considering streamflow as a low dimensional chaotic system than as a stochastic system.

Synthesis, crystal structure, DNA binding and cleavage activities of oximato bridged cationic dinuclear copper(II) complex having labile ligands

Oximato bridged dinuclear copper(II) complex Cu(L)(CH3OH)](2)(ClO4)(2) with an oxime-Schiff base ligand, viz. 3-2-(dimethylamino)ethyl]imino]-2-butanoneoxime (HL), has been synthesized and structurally characterized. The dinuclear copper(II) complex crystallizes in monoclinic space group P2(1)/n with the unit cell parameters, a = 13.3564(9) angstrom, b = 12.0821(8) angstrom, c = 17.5045(11) angstrom, beta = 90.097, V = 2824.8(3) angstrom(3), Z = 4, R = 0.0769. The complex shows quasi-reversible cyclic voltammetric response at 0.844V (Delta E-p = 276 mV) at 100 mVs(-1). The binding studies of the complex with calf thymus DNA has been investigated using absorption spectrophotometry. Cleavage activity of the complex has been carried out on double stranded pBR 322 plasmid DNA by using gel electrophoresis experiments in the absence and in the presence of the oxidant, viz., H2O2.

Synthesis, Antimicrobial and Cytotoxic Activities of Sulfonamidomethane Linked Heterocycles

A new class of sulfonamidomethane pyrrolyl-oxadiazoles/thiadiazoles and pyrazolyl-oxadiazoles/thiadiazoles was prepared from arylsulfonylaminoacetic acid hydrazides and E-cinnamic acid. The lead compounds were tested for antimicrobial and cytotoxic activities. The thiadiazole compounds having chloro substituent on the aromatic ring 4c, 8c and 10c exhibited comparable antibacterial activity against Pseudomonas aeruginosa and also antifungal activity against Penieillium ehrysogenunz. The styryl oxadiazole compound 3c showed appreciable cytotoxic activity on A549 lung carcinoma cells which can be used as a lead compound in the future studies.

Predictability and chaotic nature of daily streamflow

The predictability of a chaotic series is limited to a few future time steps due to its sensitivity to initial conditions and the exponential divergence of the trajectories. Over the years, streamflow has been considered as a stochastic system in many approaches. In this study, the chaotic nature of daily streamflow is investigated using autocorrelation function, Fourier spectrum, correlation dimension method (Grassberger-Procaccia algorithm) and false nearest neighbor method. Embedding dimensions of 6-7 obtained indicates the possible presence of low-dimensional chaotic behavior. The predictability of the system is estimated by calculating the system's Lyapunov exponent. A positive maximum Lyapunov exponent of 0.167 indicates that the system is chaotic and unstable with a maximum predictability of only 6 days. These results give a positive indication towards considering streamflow as a low dimensional chaotic system than as a stochastic system.

Synthesis, Antioxidant, and Cytotoxic Activities of N-Azole Substituted Thiomorpholine Derivatives

A new class of N-azole substituted thiomorpholine derivatives were prepared and their antioxidant and cytotoxic activities were studied. The methyl substituted oxazolyl thiomorpholine dioxide 9b exhibited radical scavenging activity greater than the standard ascorbic acid. On the other hand, the thiazolyl thiomorpholine 10c having a chloro substituent on the aromatic ring was identified as a remarkable lead molecule for cytotoxic activity against A549 and HeLa cells, with IC50 values of 10.1 and 30.0 mu M, respectively.

Synthesis, crystal structure, DNA interaction and cleavage activities of mononuclear and trinuclear copper(II) complexes

Mono- and trinuclear copper(II) complexes with 2-1-(2-dimethylamino-ethylamino)-ethyl]-phenol (HL) have been synthesized and structurally characterized. The mononuclear complex Cu(L)(H2O)(ONO2)] (1) crystallizes in monoclinic space group P2(1) /n with a square pyramidal Cu(II) center coordinated by the tridentate Schiff base (L) and a water ligand in the equatorial plane and an oxygen atom from nitrate in the axial position. The trinuclear complex (CuL)(3)(mu(3)-OH)](ClO4)(2)center dot H2O (2) crystallizes in hexagonal space group P6(3); all three copper atoms are five-coordinate with square pyramidal geometries. The interactions of these complexes with calf-thymus DNA have been investigated using absorption spectrophotometry. The mononuclear complex binds more strongly than the trinuclear complex. The DNA cleavage activity of these complexes has been studied on double-stranded pBR 322 plasmid DNA by gel electrophoresis experiments in the absence and in the presence of added oxidant (H2O2). The trinuclear complex cleaves DNA more efficiently than the mononuclear complex in the presence of H2O2.