Some implications of lepton flavor violating processes in a supersymmetric Type II seesaw model at TeV scale

We have conceived a supersymmetric Type II seesaw model at TeV scale, which has some additional particles consisting of scalar and fermionic triplet Higgs states, whose masses are around a few hundred GeV. In this particular model, we have studied constraints on the masses of triplet states arising from the lepton flavor violating (LFV) processes, such as mu -> 3e and mu -> e gamma. We have analyzed the implications of these constraints on other observable quantities such as the muon anomalous magnetic moment and the decay patterns of scalar triplet Higgses. Scalar triplet Higgs states can decay into leptons and into supersymmetric fields. We have found that the constraints from LFV can affect these various decay modes.

Revisiting lepton flavor violation in a supersymmetric type II seesaw mechanism

In view of the recent measurement of the reactor mixing angle theta(13) and updated limit on BRd(mu -> e gamma) by the MEG experiment, we reexamine the charged lepton flavor violations in a framework of the supersymmetric type II seesaw mechanism. The supersymmetric type II seesaw predicts a strong correlation between BR(mu -> e gamma) and BR(tau -> mu gamma) mainly in terms of the neutrino mixing angles. We show that such a correlation can be determined accurately after the measurement of theta(13). We compute different factors that can affect this correlation and show that the minimal supergravity-like scenarios, in which slepton masses are taken to be universal at the high scale, predict 3.5 <= BR(tau -> mu gamma)/= BR(mu -> e gamma) <= 30 for normal hierarchical neutrino masses. Any experimental indication of deviation from this prediction would rule out the minimal models of the supersymmetric type II seesaw. We show that the current MEG limit puts severe constraints on the light sparticle spectrum in the minimal supergravity model if the seesaw scale lies within 10(13)-10(15) GeV. It is shown that these constraints can be relaxed and a relatively light sparticle spectrum can be obtained in a class of models in which the soft mass of a triplet scalar is taken to be nonuniversal at the high scale.

The sequence and structure of snake gourd (Trichosanthes anguina) seed lectin, a three-chain nontoxic homologue of type II RIPs

The sequence and structure of snake gourd seed lectin (SGSL), a nontoxic homologue of type II ribosome-inactivating proteins (RIPs), have been determined by mass spectrometry and X-ray crystallography, respectively. As in type II RIPs, the molecule consists of a lectin chain made up of two beta-trefoil domains. The catalytic chain, which is connected through a disulfide bridge to the lectin chain in type II RIPs, is cleaved into two in SGSL. However, the integrity of the three-dimensional structure of the catalytic component of the molecule is preserved. This is the first time that a three-chain RIP or RIP homologue has been observed. A thorough examination of the sequence and structure of the protein and of its interactions with the bound methyl-alpha-galactose indicate that the nontoxicity of SGSL results from a combination of changes in the catalytic and the carbohydrate-binding sites. Detailed analyses of the sequences of type II RIPs of known structure and their homologues with unknown structure provide valuable insights into the evolution of this class of proteins. They also indicate some variability in carbohydrate-binding sites, which appears to contribute to the different levels of toxicity exhibited by lectins from various sources.

Nucleosynthesis in the accretion disks of type II collapsars

We investigate nucleosynthesis inside the gamma-ray burst (GRB) accretion disks formed by the Type II collapsars. In these collapsars, the core collapse of massive stars first leads to the formation of a proto-neutron star. After that, an outward moving shock triggers a successful supernova. However, the supernova ejecta lacks momentum and within a few seconds the newly formed neutron star gets transformed to a stellar mass black hole via massive fallback. The hydrodynamics of such an accretion disk formed from the fallback material of the supernova ejecta has been studied extensively in the past. We use these well-established hydrodynamic models for our accretion disk in order to understand nucleosynthesis, which is mainly advection dominated in the outer regions. Neutrino cooling becomes important in the inner disk where the temperature and density are higher. The higher the accretion rate (M) over dot is, the higher the density and temperature are in the disks. We deal with accretion disks with relatively low accretion rates: 0.001 M-circle dot s(-1) less than or similar to (M) over dot less than or similar to 0.01 M-circle dot s(-1) and hence these disks are predominantly advection dominated. We use He-rich and Si-rich abundances as the initial condition of nucleosynthesis at the outer disk, and being equipped with the disk hydrodynamics and the nuclear network code, we study the abundance evolution as matter inflows and falls into the central object. We investigate the variation in the nucleosynthesis products in the disk with the change in the initial abundance at the outer disk and also with the change in the mass accretion rate. We report the synthesis of several unusual nuclei like P-31, K-39, Sc-43, Cl-35 and various isotopes of titanium, vanadium, chromium, manganese and copper. We also confirm that isotopes of iron, cobalt, nickel, argon, calcium, sulphur and silicon get synthesized in the disk, as shown by previous authors. Much of these heavy elements thus synthesized are ejected from the disk via outflows and hence they should leave their signature in observed data.

Nucleosynthesis in the outflows associated with accretion disks of type II collapsars

We investigate nucleosynthesis inside the outflows from gamma-ray burst (GRB) accretion disks formed by the Type II collapsars. In these collapsars, massive stars undergo core collapse to form a proto-neutron star initially, and a mild supernova (SN) explosion is driven. The SN ejecta lack momentum, and subsequently this newly formed neutron star gets transformed to a stellar mass black hole via massive fallback. The hydrodynamics and the nucleosynthesis in these accretion disks have been studied extensively in the past. Several heavy elements are synthesized in the disk, and much of these heavy elements are ejected from the disk via winds and outflows. We study nucleosynthesis in the outflows launched from these disks by using an adiabatic, spherically expanding outflow model, to understand which of these elements thus synthesized in the disk survive in the outflow. While studying this, we find that many new elements like isotopes of titanium, copper, zinc, etc., are present in the outflows. Ni-56 is abundantly synthesized in most of the cases in the outflow, which implies that the outflows from these disks in a majority of cases will lead to an observable SN explosion. It is mainly present when outflow is considered from the He-rich, Ni-56/Fe-54-rich zones of the disks. However, outflow from the Si-rich zone of the disk remains rich in silicon. Although emission lines of many of these heavy elements have been observed in the X-ray afterglows of several GRBs by Chandra, BeppoSAX, XMM-Newton, etc., Swift seems to have not yet detected these lines.

Inhibition of Mycobacterium tuberculosis topoisomerase I by m-AMSA, a eukaryotic type II topoisomerase poison

m-AMSA, an established inhibitor of eukaryotic type II topoisomerases, exerts its cidal effect by binding to the enzyme-DNA complex thus inhibiting the DNA religation step. The molecule and its analogues have been successfully used as chemotherapeutic agents against different forms of cancer. After virtual screening using a homology model of the Mycobacterium tuberculosis topoisomerase I, we identified m-AMSA as a high scoring hit. We demonstrate that m-AMSA can inhibit the DNA relaxation activity of topoisomerase I from M. tuberculosis and Mycobacterium smegmatis. In a whole cell assay, m-AMSA inhibited the growth of both the mycobacteria. (C) 2014 Elsevier Inc. All rights reserved.

FOLD TYPE II PYRIDOXAL 5 `-PHOSPHATE DEPENDENT ENZYMES: STRUCTURE, SUBSTRATE RECOGNITION AND CATALYSIS

Enzymes utilizing pyridoxal 5'-phosphate dependent mechanism for catalysis are observed in all cellular forms of living organisms. PLP-dependent enzymes catalyze a wide variety of reactions involving amino acid substrates and their analogs. Structurally, these ubiquitous enzymes have been classified into four major fold types. We have carried out investigations on the structure and function of fold type I enzymes serine hydroxymethyl transferase and acetylornithine amino transferase, fold type n enzymes catabolic threonine deaminase, D-serine deaminase, D-cysteine desulfhydrase and diaminopropionate ammonia lyase. This review summarizes the major findings of investigations on fold type II enzymes in the context of similar studies on other PLP-dependent enzymes. Fold type II enzymes participate in pathways of both degradation and synthesis of amino acids. Polypeptide folds of these enzymes, features of their active sites, nature of interactions between the cofactor and the polypeptide, oligomeric structure, catalytic activities with various ligands, origin of specificity and plausible regulation of activity are briefly described. Analysis of the available crystal structures of fold type II enzymes revealed five different classes. The dimeric interfaces found in these enzymes vary across the classes and probably have functional significance.

Structural studies on a non-toxic homologue of type II RIPs from bitter gourd: Molecular basis of non-toxicity, conformational selection and glycan structure

The structures of nine independent crystals of bitter gourd seed lectin (BGSL), a non-toxic homologue of type II RIPs, and its sugar complexes have been determined. The four-chain, two-fold symmetric, protein is made up of two identical two-chain modules, each consisting of a catalytic chain and a lectin chain, connected by a disulphide bridge. The lectin chain is made up of two domains. Each domain carries a carbohydrate binding site in type II RIPs of known structure. BGSL has a sugar binding site only on one domain, thus impairing its interaction at the cell surface. The adenine binding site in the catalytic chain is defective. Thus, defects in sugar binding as well as adenine binding appear to contribute to the non-toxicity of the lectin. The plasticity of the molecule is mainly caused by the presence of two possible well defined conformations of a surface loop in the lectin chain. One of them is chosen in the sugar complexes, in a case of conformational selection, as the chosen conformation facilitates an additional interaction with the sugar, involving an arginyl residue in the loop. The N-glycosylation of the lectin involves a plant-specific glycan while that in toxic type II RIPs of known structure involves a glycan which is animal as well as plant specific.

Vortex breaking and cutting in type II superconductors.

In technological superconductors, the Lorentz force on the flux vortices is opposed by inhomogeneous pinning and so the critical current may be controlled by a combination of vortex entanglement, cutting, and cross-joining. To understand the roles of these processes we report measurements of structures in which a weak pinning layer is sandwiched between two strongly pinning leads. Quantitative modeling of the results demonstrates that in such systems the critical current is limited by the deformation of individual vortices and not by subsequent cross-joining processes.

Brain type II calcium and calmodulin-dependent protein kinase: characterization of a brain-region specific isozyme and regulation by autophosphorylation

A variety of molecular approaches have been used to investigate the structural and enzymatic properties of rat brain type ll Ca^(2+) and calmodulin-dependent protein kinase (type ll CaM kinase). This thesis describes the isolation and biochemical characterization of a brain-region specific isozyme of the kinase and also the regulation the kinase activity by autophosphorylation.

The cerebellar isozyme of the type ll CaM kinase was purified and its biochemical properties were compared to the forebrain isozyme. The cerebellar isozyme is a large (500-kDa) multimeric enzyme composed of multiple copies of 50-kDa α subunits and 60/58-kDa β/β’ subunits. The holoenzyme contains approximately 2 α subunits and 8 β subunits. This contrasts to the forebrain isozyme, which is also composed of and β/β'subunits, but they are assembled into a holoenzyme of approximately 9 α subunits and 3 β/β ' subunits. The biochemical and enzymatic properties of the two isozymes are similar. The two isozymes differ in their association with subcellular structures. Approximately 85% of the cerebellar isozyme, but only 50% of the forebrain isozyme, remains associated with the particulate fraction after homogenization under standard conditions. Postsynaptic densities purified from forebrain contain the forebrain isozyme, and the kinase subunits make up about 16% of their total protein. Postsynaptic densities purified from cerebellum contain the cerebellar isozyme, but the kinase subunits make up only 1-2% of their total protein.

The enzymatic activity of both isozymes of the type II CaM kinase is regulated by autophosphorylation in a complex manner. The kinase is initially completely dependent on Ca^(2+)/calmodulin for phosphorylation of exogenous substrates as well as for autophosphorylation. Kinase activity becomes partially Ca^(2+) independent after autophosphorylation in the presence of Ca^(2+)/calmodulin. Phosphorylation of only a few subunits in the dodecameric holoenzyme is sufficient to cause this change, suggesting an allosteric interaction between subunits. At the same time, autophosphorylation itself becomes independent of Ca^(2+) These observations suggest that the kinase may be able to exist in at least two stable states, which differ in their requirements for Ca^(2+)/calmodulin.

The autophosphorylation sites that are involved in the regulation of kinase activity have been identified within the primary structure of the α and β subunits. We used the method of reverse phase-HPLC tryptic phosphopeptide mapping to isolate individual phosphorylation sites. The phosphopeptides were then sequenced by gas phase microsequencing. Phosphorylation of a single homologous threonine residue in the α and β subunits is correlated with the production of the Ca^(2+) -independent activity state of the kinase. In addition we have identified several sites that are phosphorylated only during autophosphorylation in the absence of Ca^(2+)/ calmodulin.

Radio frequency studies of surface resistance and critical magnetic field of type I and type II superconductors

The surface resistance and the critical magnetic field of lead electroplated on copper were studied at 205 MHz in a half-wave coaxial resonator. The observed surface resistance at a low field level below 4.2°K could be well described by the BCS surface resistance with the addition of a temperature independent residual resistance. The available experimental data suggest that the major fraction of the residual resistance in the present experiment was due to the presence of an oxide layer on the surface. At higher magnetic field levels the surface resistance was found to be enhanced due to surface imperfections.

The attainable rf critical magnetic field between 2.2°K and T_c of lead was found to be limited not by the thermodynamic critical field but rather by the superheating field predicted by the one-dimensional Ginzburg-Landau theory. The observed rf critical field was very close to the expected superheating field, particularly in the higher reduced temperature range, but showed somewhat stronger temperature dependence than the expected superheating field in the lower reduced temperature range.

The rf critical magnetic field was also studied at 90 MHz for pure tin and indium, and for a series of SnIn and InBi alloys spanning both type I and type II superconductivity. The samples were spherical with typical diameters of 1-2 mm and a helical resonator was used to generate the rf magnetic field in the measurement. The results of pure samples of tin and indium showed that a vortex-like nucleation of the normal phase was responsible for the superconducting-to-normal phase transition in the rf field at temperatures up to about 0.98-0.99 T_c' where the ideal superheating limit was being reached. The results of the alloy samples showed that the attainable rf critical fields near T_c were well described by the superheating field predicted by the one-dimensional GL theory in both the type I and type II regimes. The measurement was also made at 300 MHz resulting in no significant change in the rf critical field. Thus it was inferred that the nucleation time of the normal phase, once the critical field was reached, was small compared with the rf period in this frequency range.

Molecular cloning, characterization and localization of chicken type II procollagen gene

Chicken type II procollagen (ccol2a1) has become as an important oral tolerance protein for effective treatment of rheumatoid arthritis. However, its molecular identity remains unclear. Here, we reported the full-length cDNA and nearly complete genomic DN

Functional characterization of the human-specific (type II) form of kallikrein 8, a gene involved in learning and memory

Kallikrein 8 (KLK8) is a serine protease functioning in the central nervous system, and essential in many aspects of neuronal activities. Sequence comparison and gene expression analysis among diverse primate species identified a human-specific splice for