Evaluation of DNA binding, antioxidant and cytotoxic activity of mononuclear Co(III) complexes of 2-oxo-1,2-dihydrobenzoh]quinoline-3-carbaldehyde thiosemicarbazones

Four new 2-oxo-1,2-dihydrobenzoh]quinoline-3-carbaldehyde N-substituted thiosemicarbazone ligands (H-2-LR, where R = H, Me, Et or Ph) and their corresponding new cobalt(III) complexes have been synthesized and characterized. The structures of the complexes 2 and 3 were determined by single crystal X-ray diffraction analysis. The interactions of the new complexes with DNA were investigated by absorption, emission and viscosity studies which indicated that the complexes bind to DNA via intercalation. Antioxidant studies of the new complexes showed that the significant antioxidant activity against DPPH radical. In addition, the in vitro cytotoxicity of complexes 1-4 against A549 cell line was assayed which showed higher cytotoxic activity with lower IC50 values indicating their efficiency in killing the cancer cells even at very low concentrations. (C) 2012 Elsevier Masson SAS. All rights reserved.

Further evidence for room temperature, indentation-induced nanocrystallization in a bulk metallic glass

Room temperature nanoindentation experiments, employing two different pyramidal (Berkovich and cube-corner) indenters, were performed on a Zr-based bulk metallic glass (BMG) to critically examine the possibility of indentation-induced nanocrystallization in BMGs. Cross-sectional transmission electron microscopy images obtained from high angle annular dark field ( HAADF) and high resolution (HR) modes clearly indicate to the occurrence of nanocrystallization. Pronounced nanocrystallite formation in the case of sharper cube-corner indenter suggests that the structural transformation is favored by the high strains introduced during nanoindentation. (c) 2012 Elsevier B.V. All rights reserved.

A cyclic peptide mimic of an RNA recognition motif of human La protein is a potent inhibitor of hepatitis C virus

Due to limited available therapeutic options, developing new lead compounds against hepatitis C virus is an urgent need. Human La protein stimulates hepatitis C virus translation through interaction with the hepatitis C viral RNA. A cyclic peptide mimicking the beta-turn of the human La protein that interacts with the viral RNA was synthesized. It inhibits hepatitis C viral RNA translation significantly better than the corresponding linear peptide at longer post-treatment times. The cyclic peptide also inhibited replication as measured by replicon RNA levels using real time RT-PCR. The cyclic peptide emerges as a promising lead compound against hepatitis C.

Biochemical characterization of C4 protein of cotton leaf curl Kokhran virus-Dabawali

Background: Cotton leaf curl Kokhran Virus-Dabawali (CLCuKV-Dab) is a monopartite begomovirus encoding two proteins V1 and V2 in the virion sense and four proteins Cl, C2, C3 and C4 in the complementary sense. The C4 protein of monopartite begomoviruses has been implicated to play a role in symptom determination and virus movement. The present work aims at the biochemical characterization of this protein. Methods: The C4 protein of CLCuKV-Dab was purified in fusion with GST and tested for the ability to hydrolyze ATP and other phosphate containing compounds. ATPase activity was assayed by using radiolabeled gamma-32P]-ATP and separating the product of reaction by thin layer chromatography. The hydrolysis of other compounds was monitored by the formation of a blue colored phosphomolybdate complex which was estimated by measuring the absorbance at 655 nm. Results: The purified GST-C4 protein exhibited metal ion dependent ATPase and inorganic pyrophosphatase activities. Deletion of a sequence resembling the catalytic motif present in phosphotyrosine phosphatases resulted in 70% reduction in both the activities. Mutational analysis suggested arginine 13 to be catalytically important for the ATPase and cysteine 8 for the pyrophosphatase activity of GST-C4. Interaction of V2 with GST-C4 resulted in an increase in both the enzymatic activities of GST-C4. Conclusions: The residues important for the enzymatic activities of GST-C4 are present in a motif different from the classical Walker motifs and the non-classical ATP binding motifs reported so far. General significance: The C4 protein of CLCuKV-Dab, a putative natively unfolded protein, exhibits enzymatic activities.

Photocytotoxicity of copper(II) complexes of curcumin and N-ferrocenylmethyl-L-amino acids

Copper(II) complexes Cu(Fc-aa)(cur)] (1-3) of curcumin (Hcur) and N-ferrocenylmethyl-L-amino acids (Fc-aa), viz., ferrocenylmethyl-L-tyrosine (Fc-TyrH), ferrocenylmethyl-L-tryptophan (Fc-TrpH) and ferrocenylmethyl-L-methionine (Fc-MetH), were prepared and characterized. The DNA photocleavage activity, photocytotoxicity and cellular localization in HeLa and MCF-7 cancer cells of these complexes were studied. Acetylacetonate (acac) complexes Cu(Fc-aa)(acac)] (4-6) were prepared and used as controls. The chemical nuclease inactive complexes showed efficient pUC19 DNA cleavage activity in visible light. Complexes 1-3 showed high photocytotoxicity with low dark toxicity thus giving remarkable photodynamic effect. FACScan analysis showed apoptosis of the cancer cells. Fluorescence microscopic studies revealed primarily cytosolic localization of the complexes. (C) 2013 Elsevier Masson SAS. All rights reserved.

The design of polyaniline based sensor for the qualitative estimation of malonaldehyde

The detection of contaminated food in every stage of processing required new technology for fast identification and isolation of toxicity in food. Since effect of food contaminant are severe to human health, the need of pioneer technologies also increasing over last few decades. In the current study, MDA was prepared by hydrolysis of 1,1,3,3-tetramethoxypropane in HCl media and used in the electrochemical studies. The electrochemical sensor was fabricated with modified glassy carbon electrode with polyaniline. These sensors were used for detection of sodium salt of malonaldehyde and observed that a high sensitivity in the concentration range similar to 1 x 10(-1) M and 1 x 10(-2) M. Tafel plots show the variation of over potential from -1.73 V to -3.74 V up to 10(-5) mol/L indicating the lower limit of detection of the system. (C) 2013 Elsevier Ltd. All rights reserved.

Estimating the fraction of progeny virions that must incorporate APOBEC3G for suppression of productive HIV-1 infection

The contest between the host factor APOBEC3G (A3G) and the HIV-1 protein Vif presents an attractive target of intervention. The extent to which the A3G-Vif interaction must be suppressed to tilt the balance in favor of A3G remains unknown. We employed stochastic simulations and mathematical modeling of the within-host dynamics and evolution of HIV-1 to estimate the fraction of progeny virions that must incorporate A3G to render productive infection unsustainable. Using three different approaches, we found consistently that a transition from sustained infection to suppression of productive infection occurred when the latter fraction exceeded similar to 0.8. The transition was triggered by A3G-induced hypermutations that led to premature stop codons compromising viral production and was consistent with driving the basic reproductive number, R-o, below unity. The fraction identified may serve as a quantitative guideline for strategies targeting the A3G-Vif axis. (C) 2013 Elsevier Inc. All rights reserved.

Filling-in Void and Sparse Regions in Protein Sequence Space by Protein-Like Artificial Sequences Enables Remarkable Enhancement in Remote Homology Detection Capability

Protein functional annotation relies on the identification of accurate relationships, sequence divergence being a key factor. This is especially evident when distant protein relationships are demonstrated only with three-dimensional structures. To address this challenge, we describe a computational approach to purposefully bridge gaps between related protein families through directed design of protein-like ``linker'' sequences. For this, we represented SCOP domain families, integrated with sequence homologues, as multiple profiles and performed HMM-HMM alignments between related domain families. Where convincing alignments were achieved, we applied a roulette wheel-based method to design 3,611,010 protein-like sequences corresponding to 374 SCOP folds. To analyze their ability to link proteins in homology searches, we used 3024 queries to search two databases, one containing only natural sequences and another one additionally containing designed sequences. Our results showed that augmented database searches showed up to 30% improvement in fold coverage for over 74% of the folds, with 52 folds achieving all theoretically possible connections. Although sequences could not be designed between some families, the availability of designed sequences between other families within the fold established the sequence continuum to demonstrate 373 difficult relationships. Ultimately, as a practical and realistic extension, we demonstrate that such protein-like sequences can be ``plugged-into'' routine and generic sequence database searches to empower not only remote homology detection but also fold recognition. Our richly statistically supported findings show that complementary searches in both databases will increase the effectiveness of sequence-based searches in recognizing all homologues sharing a common fold. (C) 2013 Elsevier Ltd. All rights reserved.

Cost-effective wear and oxidation resistant electrodeposited Ni-pumice coating

In the search for newer distributed phases that can be used in Ni-composite coatings, inexpensive and naturally available pumice has been identified as a potential candidate material. The composition of the pumice mineral as determined by Rietveld analysis shows the presence of corundum, quartz, mulllite, moganite and coesite phases. Pumice stone is crushed, ball-milled, dried and dispersed in a nickel sulfamate bath and Ni-pumice coatings are electrodeposited at different current densities and magnetic agitation speeds. Pumice particles are uniformly incorporated in the nickel matrix and Ni-pumice composite coatings with microhardness as high as 540 HK are obtained at the lowest applied current density. In the electrodeposited Ni-pumice coatings, the grain size of Ni increases with the applied current density. The overall intensity of texture development is slightly stronger for the Ni-pumice composite coating compared to plain Ni coating and the texture evolution is possibly not the strongest deciding factor for the enhanced properties of Ni-pumice coatings. The wear and oxidation resistances of Ni-pumice coating are commensurate with that of Ni-SiC coating electrodeposited under similar conditions. (C) 2014 Elsevier B.V. All rights reserved.

Antioxidant activity and electrochemical elucidation of the enigmatic redox behavior of curcumin and its structurally modified analogues

Here, we report studies on the antioxidant activity and redox behavior of curcumin and its structurally modified synthetic analogues. We have synthesized a number of analogues of curcumin which abrogate its keto-enol tautomerism or substitute the methylene group at the centre of its heptadione moiety implicated in the hydride transfer and studied their redox property. From cyclic voltammetric studies, it is demonstrated that H-atom transfer from CH2 group at the center of the heptadione link also plays an important role in the antioxidant properties of curcumin along with that of its phenolic -OH group. In addition, we also show that the conversion of 1, 3-dicarbonyl moiety of curcumin to an isosteric heterocycle as in pyrazole curcumin, which decreases its rotational freedom, leads to an improvement of its redox properties as well as its antioxidant activity. (C) 2014 Elsevier Ltd. All rights reserved.

Effect of sputtering parameters on the structure, microstructure and magnetic properties of Tb-Fe films

The effect of sputtering parameters such as gas pressure and power on the structure, microstructure and magnetic properties of sputtered Tb-Fe thin films was investigated. X-ray diffraction and transmission electron microscopy studies showed that all the films were amorphous in nature irrespective of the sputtering parameters. A fine island kind of morphology was observed at low sputtering power whereas large clusters were seen at higher sputtering power. While the composition of Tb-Fe films remained constant with increasing sputtering power, the magnetic behaviour was found to change from superparamagnetic to ferromagnetic. On the other hand, the increase in argon gas pressure was found to deplete the iron concentration in Tb-Fe thin films, which in turn reduced the anisotropy and Curie temperature. Annealing of the films at 773 K did not result in any crystallization and the magnetic properties were also found to remain unchanged. (C) 2015 Elsevier B.V. All rights reserved.

Analytical approach to quantile estimation in regional frequency analysis based on fuzzy framework

Regional frequency analysis is widely used for estimating quantiles of hydrological extreme events at sparsely gauged/ungauged target sites in river basins. It involves identification of a region (group of watersheds) resembling watershed of the target site, and use of information pooled from the region to estimate quantile for the target site. In the analysis, watershed of the target site is assumed to completely resemble watersheds in the identified region in terms of mechanism underlying generation of extreme event. In reality, it is rare to find watersheds that completely resemble each other. Fuzzy clustering approach can account for partial resemblance of watersheds and yield region(s) for the target site. Formation of regions and quantile estimation requires discerning information from fuzzy-membership matrix obtained based on the approach. Practitioners often defuzzify the matrix to form disjoint clusters (regions) and use them as the basis for quantile estimation. The defuzzification approach (DFA) results in loss of information discerned on partial resemblance of watersheds. The lost information cannot be utilized in quantile estimation, owing to which the estimates could have significant error. To avert the loss of information, a threshold strategy (TS) was considered in some prior studies. In this study, it is analytically shown that the strategy results in under-prediction of quantiles. To address this, a mathematical approach is proposed in this study and its effectiveness in estimating flood quantiles relative to DFA and TS is demonstrated through Monte-Carlo simulation experiments and case study on Mid-Atlantic water resources region, USA. (C) 2015 Elsevier B.V. All rights reserved.

Formal synthesis of degraded sterol (+)-aplykurodinone-1

The formal synthesis of aplykurodinone-1 is accomplished starting from a suitably functionalized bicyclic lactone having the requisite cis-fused ring junction with a quaternary chiral center that was assembled following a Cp2TiCl-mediated radical cyclization protocol. Our synthetic route further elaborates implementation of Grubbs ring closing metathesis (RCM), Eschenmoser-Claisen rearrangement and iodo-lactonization reactions for the synthesis of the final tricyclic precursor of the target molecule. (C) 2015 Elsevier Ltd. All rights reserved.

A carboxy terminal domain of the L protein of rinderpest virus possesses RNA triphosphatase activity - The first enzyme in the viral mRNA capping pathway

The large protein L of negative-sense RNA viruses is a multifunctional protein involved in transcription and replication of genomic RNA. It also possesses enzymatic activities involved in capping and methylation of viral mRNAs. The pathway for mRNA capping followed by the L protein of the viruses in the Morbillivirus genus has not been established, although it has been speculated that these viruses may follow the unconventional capping pathway as has been shown for some viruses of Rhabdoviridae family. We had earlier shown that the large protein L of Rinderpest virus expressed as recombinant L-P complex in insect cells as well as the ribonucleoprotein complex from purified virus possesses RNA triphosphatase (RTPase) and guanylyltransferase activities, in addition to RNA dependent RNA polymerase activity. In the present work, we demonstrate that RTPase as well as nucleoside triphosphatase (NTPase) activities are exhibited by a subdomain of the L protein in the C terminal region (a.a. 1640 1840). The RTPase activity depends absolutely on a divalent cation, either magnesium or manganese. Both the RTPase and NTPase activities of the protein show dual metal specificity. Two mutant proteins having alanine mutations in the glutamic acid residues in motif-A of the RTPase domain did not show RTPase activity, while exhibiting reduced NTPase activity suggesting overlapping active sites for the two enzymatic functions. The RTPase and NTPase activities of the L subdomain resemble those of the Vaccinia capping enzyme D1 and the baculovirus LEF4 proteins. (C) 2015 Elsevier Inc. All rights reserved.

A micropolar cohesive damage model for delamination of composites

A micropolar cohesive damage model for delamination of composites is proposed. The main idea is to embed micropolarity, which brings an additional layer of kinematics through the micro-rotation degrees of freedom within a continuum model to account for the micro-structural effects during delamination. The resulting cohesive model, describing the modified traction separation law, includes micro-rotational jumps in addition to displacement jumps across the interface. The incorporation of micro-rotation requires the model to be supplemented with physically relevant material length scale parameters, whose effects during delamination of modes I and II are brought forth using numerical simulations appropriately supported by experimental evidences. (C) 2015 Elsevier Ltd. All rights reserved.