Process Development for Functionalization of Cotton with Silver Nanoparticles Synthesized by Bio-based Approaches

Cotton is a widely used raw material for textiles but drawbacks regarding their poor mechanical properties often limit their applications as functional materials. The present investigation involved process development for one step coating of cotton with silver nanoparticles (SNP) synthesized using Azadirachta indica and Citrus limon extract to develop functional textiles. Addition of starch to functional textiles led to efficient binding of nanoparticles to fabric and led to drastic decrease in release of silver from fabricated textiles after ten washing cycles enhancing their environment friendliness. Differential scanning calorimetry, scanning electron microscopy, FT-IR analysis and mechanical studies demonstrated efficient binding of nanoparticles to fabric through bio-based processes. The functionalized textiles developed by the bio-based methods showed significant antibacterial activity against E. coli and S. aureus (with 99% microbial reduction). Present work offers a simple procedure for coating SNP using bio-based approaches with promising applications in specialized functions.

Gene Transfection in High Serum Levels: Case Studies with New Cholesterol Based Cationic Gemini Lipids

Background: Six new cationic gemini lipids based on cholesterol possessing different positional combinations of hydroxyethyl (-CH2CH2OH) and oligo-oxyethylene -(CH2CH2O)(n)- moieties were synthesized. For comparison the corresponding monomeric lipid was also prepared. Each new cationic lipid was found to form stable, clear suspensions in aqueous media. Methodology/Principal Findings: To understand the nature of the individual lipid aggregates, we have studied the aggregation properties using transmission electron microscopy (TEM), dynamic light scattering (DLS), zeta potential measurements and X-ray diffraction (XRD). We studied the lipid/DNA complex (lipoplex) formation and the release of the DNA from such lipoplexes using ethidium bromide. These gemini lipids in presence of a helper lipid, 1, 2-dioleoyl phophatidyl ethanol amine (DOPE) showed significant enhancements in the gene transfection compared to several commercially available transfection agents. Cholesterol based gemini having -CH2-CH2-OH groups at the head and one oxyethylene spacer was found to be the most effective lipid, which showed transfection activity even in presence of high serum levels (50%) greater than Effectene, one of the potent commercially available transfecting agents. Most of these geminis protected plasmid DNA remarkably against DNase I in serum, although the degree of stability was found to vary with their structural features. Conclusions/Significance: -OH groups present on the cationic headgroups in combination with oxyethylene linkers on cholesterol based geminis, gave an optimized combination of new genera of gemini lipids possessing high transfection efficiency even in presence of very high percentage of serum. This property makes them preferential transfection reagents for possible in vivo studies.

Synthesis, structure, characterization and photocatalytic activity of Bi2Zr2O7 under solar radiation

Bi2Zr2O7 was synthesized via a facile solution combustion method. Two different fuels, urea and tartaric acid were used in the synthesis, which resulted in Bi2Zr2O7 crystals with different band gaps and surface areas. The structure has been determined by Rietveld refinement followed by the difference Fourier technique. The compound crystallizes in the space group Fm (3) over barm. The photocatalytic degradation of two dyes was carried out under solar radiation. Bi2Zr2O7 prepared using urea as the fuel exhibits a higher photocatalytic activity than the compound prepared using tartaric acid and comparable activity to that of commercial Evonik P-25 TiO2. It is suggested that this is due to the oxygen vacancies occurring in the two cases, the urea based compound has an occupancy of 0.216, whereas the tartaric acid based synthesis shows disorder in the oxygen position amounting to a small number of oxygen vacancies.

Inhibition of Lactoperoxidase-Catalyzed Oxidation by Imidazole-Based Thiones and Selones: A Mechanistic Study

Herein, we describe the synthesis and biomimetic activity of a series of N,N-disubstituted thiones and selones that contain an imidazole pharmacophore. The N,N-disubstituted thiones do not show any inhibitory activity towards LPO-catalyzed oxidation reactions, but their corresponding N,N-disubstituted selones exhibit inhibitory activity towards LPO-catalyzed oxidation reactions. Substituents on the N atom of the imidazole ring appear to have a significant effect on the inhibition of LPO-catalyzed oxidation and iodination reactions. Selones 16, 17, and 19, which contain methyl, ethyl, and benzyl substituents, exhibit similar inhibition activities towards LPO-catalyzed oxidation reactions with IC50 values of 24.4, 22.5, and 22.5M, respectively. However, their activities are almost three-fold lower than that of the commonly used anti-thyroid drug methimazole (MMI). In contrast, selone 21, which contains a NCH2CH2OH substituent, exhibits high inhibitory activity, with an IC50 value of 7.2M, which is similar to that of MMI. The inhibitory activity of these selones towards LPO-catalyzed oxidation/iodination reactions is due to their ability to decrease the concentrations of the co-substrates (H2O2 and I2), either by catalytically reducing H2O2 (anti-oxidant activity) or by forming stable charge-transfer complexes with oxidized iodide species. The inhibition of LPO-catalyzed oxidation/iodination reactions by N,N-disubstituted selones can be reversed by increasing the concentration of H2O2. Interestingly, all of the N,N-disubstituted selones exhibit high anti-oxidant activities and their glutathione peroxidase (GPx)-like activity is 4-12-fold higher than that of the well-known GPx-mimic ebselen. These experimental and theoretical studies suggest that the selones exist as zwitterions, in which the imidazole ring contains a positive charge and the selenium atom carries a large negative charge. Therefore, the selenium moieties of these selones possess highly nucleophilic character. The 77SeNMR chemical shifts for the selones show large upfield shift, thus confirming the zwitterionic structure in solution.

STUDENT'S-t MIXTURE MODEL BASED MULTI-INSTRUMENT RECOGNITION IN POLYPHONIC MUSIC

We address the problem of multi-instrument recognition in polyphonic music signals. Individual instruments are modeled within a stochastic framework using Student's-t Mixture Models (tMMs). We impose a mixture of these instrument models on the polyphonic signal model. No a priori knowledge is assumed about the number of instruments in the polyphony. The mixture weights are estimated in a latent variable framework from the polyphonic data using an Expectation Maximization (EM) algorithm, derived for the proposed approach. The weights are shown to indicate instrument activity. The output of the algorithm is an Instrument Activity Graph (IAG), using which, it is possible to find out the instruments that are active at a given time. An average F-ratio of 0 : 7 5 is obtained for polyphonies containing 2-5 instruments, on a experimental test set of 8 instruments: clarinet, flute, guitar, harp, mandolin, piano, trombone and violin.

Identification and characterization of novel indole based small molecules as anticancer agents through SIRT1 inhibition

In our pursuit to develop new potential anticancer leads, we designed a combination of structural units of indole and substituted triazole; and a library of 1-{1-methyl-2-4-phenyl-5-(propan-2-ylsulfanyl)-4H-1,2,4-triazol-3-yl ]-1H-indol-3-yl}methanamine derivatives was synthesized and characterized. Cytotoxic evaluations of these molecules over a panel of three human cancer cell lines were carried out. Few molecules exhibited potent growth inhibitory action against the treated cancer cell lines at lower micro molar concentration. An in vitro assay investigation of these active compounds using recombinant human SIRT1 enzyme showed that one of the compounds (IT-14) inhibited the deacetylation activity of the enzyme. The in vivo study of IT-14 exemplified its promising action by reducing the prostate weight to the body weight ratio in prostate hyperplasia animal models. A remarkable decrease in the disruption of histoarchitecture of the prostate tissues isolated from IT-14 treated animal compared to that of the positive control was observed. The molecular interactions with SIRT1 enzyme were also supported by molecular docking simulations. Hence this compound can act as a lead molecule to treat prostatic hyperplasia. (C) 2013 Elsevier Masson SAS. All rights reserved.

A cationic cholesterol based nanocarrier for the delivery of p53-EGFP-C3 plasmid to cancer cells

The p53 protein mediated anti-tumor strategy is limited due to the lack of suitable delivery agent with insignificant immunogenic response, serum compatibility, and early and easy detection of the transfected cell population. To overcome these problems, we generated a p53-EGFP-C3 fusion construct which expressed easily detectable green fluorescence protein (GFP) and allowed an estimation of p53 mediated anti-tumor activity. A mixture of cationic cholesterol gemini (Choi-5L) with natural lipid, DOPE (molar ratio 1:4), acronymed as Chol-5LD, formed a nano-liposome as characterized by various physical methods. The prepared clone was evaluated for the expression of GFP and functional p53 in HeLa and two additional cell lines with varied p53 status namely, H1299 (p53(-/-)) and HEK293T (p53(+/+)). Transfected cells were screened using RT-PCR, Western blotting, FACS analysis, MTT, Trypan blue assay and visualized under a fluorescence microscope. The p53-EGFP-C3 fusion protein induced apoptosis in cancer cells as evident from DNA fragmentation, cell cycle analysis, Annexin-V staining and PARP cleavage assays. The transfection and apoptosis induction efficiency of Chol-5LD was significantly higher than commercial reagents Lipofectamine2000 and Effectene irrespective of the cell lines examined. Further it significantly decreases the xenograft tumor volume in nude mice tumors via apoptosis as observed in H&E staining. (C) 2013 Elsevier Ltd. All rights reserved.

Synergistic electrochemical activity of titanium carbide and carbon towards fuel cell reactions

Titanium carbide (TiC) is an electrically conducting refractory interstitial compound possessing several unique properties. A cost-effective, efficient and non-Pt electrocatalyst based on TiC is explored and the multi-functionality of TiC towards various electrochemical reactions that are of significant interest in low temperature fuel cells is studied. Ameliorated activities towards oxygen reduction reaction (ORR) and borohydride oxidation are observed with TiC-carbon composites. High sensitivity and selectivity towards ORR have been demonstrated with very good methanol tolerance. The charge transfer interactions between TiC and carbon seem to play a vital role in the improved activity as compared to their individual counterparts. The present study opens up a way to realize completely Pt-free borohydride fuel cell architecture.

Two new atom centered fragment descriptors and scoring function enhance classification of antibacterial activity

Classification of pharmacologic activity of a chemical compound is an essential step in any drug discovery process. We develop two new atom-centered fragment descriptors (vertex indices) - one based solely on topological considerations without discriminating atomor bond types, and another based on topological and electronic features. We also assess their usefulness by devising a method to rank and classify molecules with regard to their antibacterial activity. Classification performances of our method are found to be superior compared to two previous studies on large heterogeneous data sets for hit finding and hit-to-lead studies even though we use much fewer parameters. It is found that for hit finding studies topological features (simple graph) alone provide significant discriminating power, and for hit-to-lead process small but consistent improvement can be made by additionally including electronic features (colored graph). Our approach is simple, interpretable, and suitable for design of molecules as we do not use any physicochemical properties. The singular use of vertex index as descriptor, novel range based feature extraction, and rigorous statistical validation are the key elements of this study.

Synthesis and antiproliferative effect of novel 4-thiazolidinone-, pyridine- and piperazine-based conjugates on human leukemic cells

The present work reveals the synthesis and antiproliferative effect of a series of 2, 3 disubstituted 4-thiazolidinone analogues on human leukemic cells. The chemical structures of newly synthesized compounds were confirmed by IR, H-1 NMR, C-13 NMR and mass spectral analysis. Compound methyl 3-methoxy-4-(4-oxo-3-(5-(piperazin-1-yl)pyridin-2-yl)thiazolidin-2-yl)be nzoate (5) displayed potent activity (IC50 9.71, 15.24 and 19.29 mu M) against Nalm6, K562, Jurkat cells. Cell cycle analysis and mitochondrial membrane potential further confirmed that compound 5 is cytotoxic and able to induce cell death. (C) 2014 Elsevier Masson SAS. All rights reserved.

Direct control of type IIA topoisomerase activity by a chromosomally encoded regulatory protein

Precise control of supercoiling homeostasis is critical to DNA-dependent processes such as gene expression, replication, and damage response. Topoisomerases are central regulators of DNA supercoiling commonly thought to act independently in the recognition and modulation of chromosome superstructure; however, recent evidence has indicated that cells tightly regulate topoisomerase activity to support chromosome dynamics, transcriptional response, and replicative events. How topoisomerase control is executed and linked to the internal status of a cell is poorly understood. To investigate these connections, we determined the structure of Escherichia coil gyrase, a type HA topoisomerase bound to YacG, a recently identified chromosomally encoded inhibitor protein. Phylogenetic analyses indicate that YacG is frequently associated with coenzyme A (CoA) production enzymes, linking the protein to metabolism and stress. The structure, along with supporting solution studies, shows that YacG represses gyrase by sterically occluding the principal DNA-binding site of the enzyme. Unexpectedly, YacG acts by both engaging two spatially segregated regions associated with small-molecule inhibitor interactions (fluoroquinolone antibiotics and the newly reported antagonist GSK299423) and remodeling the gyrase holo enzyme into an inactive, ATP-trapped configuration. This study establishes a new mechanism for the protein-based control of topoisomerases, an approach that may be used to alter supercoiling levels for responding to changes in cellular state.

Role of Vertex Index in Substructure Identification and Activity Prediction: A Study on Antitubercular Activity of a Series of Acid Alkyl Ester Derivatives

Tuberculosis (TB) is a life threatening disease caused due to infection from Mycobacterium tuberculosis (Mtb). That most of the TB strains have become resistant to various existing drugs, development of effective novel drug candidates to combat this disease is a need of the day. In spite of intensive research world-wide, the success rate of discovering a new anti-TB drug is very poor. Therefore, novel drug discovery methods have to be tried. We have used a rule based computational method that utilizes a vertex index, named `distance exponent index (D-x)' (taken x = -4 here) for predicting anti-TB activity of a series of acid alkyl ester derivatives. The method is meant to identify activity related substructures from a series a compounds and predict activity of a compound on that basis. The high degree of successful prediction in the present study suggests that the said method may be useful in discovering effective anti-TB compound. It is also apparent that substructural approaches may be leveraged for wide purposes in computer-aided drug design.

Ferrocenyl-L-amino acid copper(II) complexes showing remarkable photo-induced anticancer activity in visible light

Ferrocene-conjugated copper(II) complexes Cu(Fc-aa)(aip)](ClO4) (1-3) and (Cu(Fc-aa)(pyip)](ClO4) (4-6) of L-amino acid reduced Schiff bases (Fc-aa), 2-(9-anthryl)-1H-imidazo4,5-f]1,10]phenanthroline (aip) and 2-(1-pyrenyl)-1H-imidazo4,5-f] 1,10]phenanthroline (pyip), where Fc-aa is ferrocenylmethyl-L-tyrosine (Fc-Tyr in 1, 4), ferrocenylmethyl-L-tryptophan (Fc-Trp in 2, 5) and ferrocenylmethyl-L-methionine (Fc-Met in 3, 6), were prepared and characterized, and their photocytotoxicity was studied (Fc = ferrocenyl moiety). Phenyl analogues, viz. (Cu(Ph-Met)(aip)](ClO4) (7) and (Cu(Ph-Met)(pyip)](ClO4) (8), were prepared and used as control compounds. The bis-imidazophenanthroline copper(II) complexes, viz. (Cu(aip)(2)(NO3)](NO3) (9) and Cu(pyip)(2)(NO3)](NO3) (10), were also prepared and used as controls. Complexes 1-6 having a redox inactive cooper(II) center showed the Fc(+)-Fc redox couple at similar to 0.5 V vs. SCE in DMF-0.1 mol (Bu4N)-N-n](ClO4). The copper(II)-based d-d band was observed near 600 nm in DMF-Tris-HCl buffer (1 :1 v/v). The ferrocenyl complexes showed low dark toxicity, but remarkably high photocytotoxicity in human cervical HeLa and human breast adenocarcinoma MCF-7 cancer cells giving an excellent photo-dynamic effect while their phenyl analogues were inactive. The photo-exposure caused significant morphological changes in the cancer cells when compared to the non-irradiated ones. The photophysical processes were rationalized from the theoretical studies. Fluorescence microscopic images showed 3 and 6 localizing predominantly in the endoplasmic reticulum (ER) of the cancer cells, thus minimizing any undesirable effects involving nuclear DNA.

A DYNAMO MODEL OF MAGNETIC ACTIVITY IN SOLAR-LIKE STARS WITH DIFFERENT ROTATIONAL VELOCITIES

We attempt to provide a quantitative theoretical explanation for the observations that Ca II H/K emission and X-ray emission from solar-like stars increase with decreasing Rossby number (i.e., with faster rotation). Assuming that these emissions are caused by magnetic cycles similar to the sunspot cycle, we construct flux transport dynamo models of 1M(circle dot) stars rotating with different rotation periods. We first compute the differential rotation and the meridional circulation inside these stars from a mean-field hydrodynamics model. Then these are substituted in our dynamo code to produce periodic solutions. We find that the dimensionless amplitude f(m) of the toroidal flux through the star increases with decreasing rotation period. The observational data can be matched if we assume the emissions to go as the power 3-4 of f(m). Assuming that the Babcock-Leighton mechanism saturates with increasing rotation, we can provide an explanation for the observed saturation of emission at low Rossby numbers. The main failure of our model is that it predicts an increase of the magnetic cycle period with increasing rotation rate, which is the opposite of what is found observationally. Much of our calculations are based on the assumption that the magnetic buoyancy makes the magnetic flux tubes rise radially from the bottom of the convection zone. Taking into account the fact that the Coriolis force diverts the magnetic flux tubes to rise parallel to the rotation axis in rapidly rotating stars, the results do not change qualitatively.

Efficacious Gene Silencing in Serum and Significant Apoptotic Activity Induction by Survivin Downregulation Mediated by New Cationic Gemini Tocopheryl Lipids

Nonviral gene delivery offers cationic liposomes as promising instruments for the delivery of double-stranded RNA (ds RNA) molecules for successful sequence-specific gene silencing (RNA interference). The efficient delivery of siRNA (small interfering RNA) to cells while avoiding unexpected side effects is an important prerequisite for the exploitation of the power of this excellent tool. We present here six new tocopherol based cationic gemini lipids, which induce substantial gene knockdown without any obvious cytotoxicity. All the efficient coliposomal formulations derived from each of these geminis and a helper lipid, dioleoylphosphatidylethanolamine (DOPE), were well characterized using physical methods such as atomic force microscopy (AFM) and dynamic light scattering (DLS). Zeta potential measurements were conducted to estimate the surface charge of these formulations. Flow cytometric analysis showed that the optimized coliposomal formulations could transfect anti-GFP siRNA efficiently in three different GFP expressing cell lines, viz., HEK 293T, HeLa, and Caco-2, significantly better than a potent commercial standard Lipofectamine 2000 (L2K) both in the absence and in the presence of serum (FBS). Notably, the knockdown activity of coliposomes of gemini lipids was not affected even in the presence of serum (10% and 50% FBS) while it dropped down for L2K significantly. Observations under a fluorescence microscope, RT-PCR, and Western blot analysis substantiated the flow cytometry results. The efficient cellular entry of labeled siRNA in GFP expressing cells as evidenced from confocal microscopy put forward these gemini lipids among the potent lipidic carriers for siRNA. The efficient transfection capabilities were also profiled in a more relevant fashion while performing siRNA transfections against survivin (an anti-apoptotic protein) which induced substantial apoptosis. Furthermore, the survivin downregulation improved the therapeutic efficacy levels of an anticancer drug, doxorubicin, significantly. In short, the new tocopherol based gemini lipids appear to be highly promising for achieving siRNA mediated gene knockdown in various cell lines.