Metal complexes of non-heme ligands: biological applications

Oxidative inactivation of proteins (carbonic anhydrase–I, trypsin, chymotrypsin and 20S proteasome) by non–heme iron complexes, and glutathionylation of non–heme cobalt complexes mimicking the N5 coordination environment like that of biologically important cofactor cobalamin or B12 (Cbl) are reported. Different non–heme ligand sets or inhibitors were used to inactivate different proteins. Carbonic anhydrase–I (CA–I) and 20S proteasome were inactivated by iron complexes in the presence of O2 and a reductant (DTT), consistent with a pathway involving the reductive activation of O2, whereas serine proteases trypsin and chymotrypsin were inactivated by ferryls (single turnover), and by an iron complex in presence of biologically relevant oxidant, H2O2 (catalytic conditions). Analysis of the CA–I inactivation products by SDS–PAGE, ESI–MS and LC/MS/MS confirmed that the protein is inactivated by oxidation of amino acid side chains (His, Trp and Met) rather than fragmentation of the protein backbone. On the other hand, amino acid analysis of serine proteases inactivation products confirmed that residues Cys, Tyr, and Trp were oxidized under single turnover condition while the residue tyrosine was oxidized selectively under catalytic conditions. Control experiments preclude the role of ROS, and supported the role of a metal-based oxidant responsible for protein inactivation in all the cases. A low spin cobalt (III) cobalamin model complex derived from a polypyridyl pentadentate N5 non–heme ligand was synthesized and characterized fully by X–ray crystallography, UV–vis, IR, 1H–NMR and 13C–NMR spectroscopies, and mass spectrometry (HRMS). Kinetic and thermodynamic studies on the reaction of this cobalt complex along with another related congener with glutathione were performed in aqueous buffer to generate biomimetic species of glutathionylcobalamin, an important form of cobalamin found in nature. The reaction follows second order kinetic, with both the rate constants and the observed equilibrium constants smaller than the rate constants and equilibrium constant of the reaction of aquacobalamin and GSH to give glutathionylcobalamin. Glutathionylation showed significant pH dependence, where rates increased with pH. Taken together, these results suggest that glutathionylation is a general reaction for Co(III) complexes related to Cbl

Electrocatalysis for oxygen electrodes in fuel cells and water electrolyzers for space applications

In most instances separate electrocatalysts are needed to promote the reduction of O2 in the fuel cell mode and to generate O2 in the energy storage-water electrolysis mode in aqueous electrochemical systems operating at low and moderate temperatures (T greater than or equal to 200 C). Interesting exceptions are the lead and bismuth ruthenate pyrochlores in alkaline electrolytes. These catalysts on high area carbon supports have high catalytic activity for both O2 reduction and generation. Rotating ring-disk electrode measurements provide evidence that the O2 reduction proceeds by a parallel four-electron pathway. The ruthenates can also be used as self-supported catalysts to avoid the problems associated with carbon oxidation, but the electrode performance so far achieved in the research at Case Western Reserve University (CWRU) is considerably less. At the potentials involved in the anodic mode the ruthenate pyrochlores have substantial equilibrium solubility in concentrated alkaline electrolyte. This results in the loss of catalyst into the bulk solution and a decline in catalytic activity. Furthermore, the hydrogen generation counter electrode may become contaminated with reduction products from the pyrochlores (lead, ruthenium)

Energy Efficient Elliptical Curve based Spherical Grid Routing Protocol for Wireless Sensor Networks

The Wireless Sensor Network (WSN) is a collection of no. of mobile nodes which communicate through wireless channel without any existing network infrastructure. Because the resource constrained nature of WSN a data packet routing requires multiple hops to exchange data across the network. In order to facilitate communication within the network, a secure energy efficient routing protocol is used to discover routes between nodes. The proposed energy efficient elliptical curve based spherical grid routing protocol for WSN provides correct and efficient route establishment between a pair of nodes so that data packets can be delivered in time to the destination. Secure route construction can be done with optimized WSN performance matrices such as packet delivery ratio, throughput, minimum energy consumptions, communication overhead

Gene expression analysis in breast cancer

Breast cancer is the most common type of cancer among females, both in incidence and death. As meaningful biological understanding of the disease is confounded by the existence of various molecular groups and sub-groups, the challenge for targeted drug development may lie in understanding the molecular mechanisms of various sub-groups in breast cancer. An in-house breast cancer gene expression dataset comprising 17 normal and 104 tumour samples was analysed to identify important genes and pathways relevant to various clinical parameters. Our results identified groups of patients with similar expression profiles, the possible biology driving them and the clinical implications. Comparing Normal and Cancer specimens’ gene expression profiles, TP53, along with cell cycle genes, were up-regulated in cancer samples. Embryonic stem cell pathway genes were up-regulated, while fatty acid biosynthesis pathways were down-regulated in tumors vs normal. The cancer specimens largely clustered with respect to ER status. Meta-analysis was performed on in-house datasets along with five public datasets to identify ER pathway genes. The analysis identified novel genes which had not been previously associated with ER-related pathways in cancer. Nuclear receptor pathways were up-regulated in ER-positive tumors/cell lines. Mining for ESR1-correlated genes across 5897 specimens identified FOXA1, SPDEF, C1ORF34 and GATA3 expression to be highly correlated. Three sub-clusters were identified among the ER-negative cluster. One represented ERBB2 over-expressing cluster. Additionally two unique groups of patients, with significant differences in survival, previously un-identified by other studies, were identified among the ER-negative cluster; a good prognosis cluster with high expression of Immune response genes; and a bad prognosis cluster with high expression of Ropporin, over-expression of which was also linked to high incidence of relapse in our study. siRNA knockdown of Ropporin (ROPN1 and ROPN1B) in the M14 melanoma cell line impaired cancer cell motility and invasion. Knockdown of ROPN1B in MDA-MB-435s reduced motility. In the first study of its kind our results validated the role of Ropporin in cancer cell motility and invasion. A list of 162 relapse-associated prognostically-important genes was used to develop a Neural Network back propagation model to predict the clinical outcomes. The model was successful in predicting relapse with 97.8% accuracy and outperformed existing models, indicating a strong possibility of its use as diagnostic model

Impact of Literacy on Juvenile Delinquency in India (with special reference to the sexual offences)

Children are the future of the country. Juvenile delinquency is the hurdle to the development of the juvenile and its effects are bad on the development of the country. Sexual offenses are social evil that badly affects to the juvenile as well as the victim woman. Juvenile criminality has been increased year by year in India particularly in juvenile sexual offenses. Even though to emphasis the literacy, there is Constitutional provision under Directive Principle of the State Policy as well as Fundamental Rights as provided under Part III & IV of the Constitution of India but there is an implemental gap. In furtherance, to give effect to rise up the literacy, the Union Government and States Government are trying to implement several policies. There are several reasons behind juvenile delinquency like- social, economic, political, psychological, and biological reasons but literacy is directly impacting on juvenile delinquency.  If we want to build a strong India then we have to make mentally strong children. The objective of the present study is to analyse the effect of literacy of the States and UTs on its juvenile delinquency. The effect of policies as initiated by the Union and State Government with respect to juvenile delinquency has also been elaborated categorically in manner. The present study is based on doctrinal and empirical methods. For doctrinal, data has been collected from the textbooks, research papers, journals, articles, and websites, and for imperial study, data has been adopted from official sites. For conclusive analysis, the statistical formulae have been applied

Optical and surface enhanced Raman scattering properties of Au nanoparticles embedded in and located on a carbonaceous matrix

Au nanoparticles (NPs) on the surface and embedded in a matrix have been the subject of studies dealing with a variety of spectroscopic and sensing applications. Here, we report on low energy Ar ion induced evolution of the morphology of a thin Au film on a polyethylene terephthalate (PET) substrate along with thermodynamic interpretations, and corresponding unique surface plasmon resonance (SPR) and photoluminescence (PL) properties. These properties are linked to the variation of surface nanostructures and the surface enhanced Raman scattering (SERS) effect of methyl orange (MO) dye molecules adsorbed on the surface. Ion induced thermal spike and sputtering resulted in dewetting of the film with subsequent formation of spherical NPs. This was followed by embedding of the NPs in the modified PET due to the thermodynamic driving forces involved. The surface and interface morphologies were studied using atomic force microscopy and cross-sectional transmission electron microscopy. X-ray photoelectron spectroscopy was used to study the chemical changes in the system upon irradiation. The optical properties were studied by diffuse reflectance UV-Vis spectroscopy and PL using a 325 nm He-Cd laser. The red shift of the SPR absorption and the blue shift of the PL emission have been correlated with the surface morphology. The blue PL emission bands at around 3.0 eV are in good agreement with the literature with respect to the morphological changes and the blue shift is attributed to compressive strain on the embedded Au NPs. Enhancement of the SERS signals is observed and found to be correlated with the SPR response of the Au nanostructures. The SERS analyses indicate that MO molecules may be adsorbed with different orientations on these surfaces i.e. Au NPs located on the surface or embedded in the modified PET. These polymeric substrates modified by NPs can have a potential application in solid-state light emitting devices and can be applied in SERS based sensors for the detection of organic compounds