Promotion of fibronectin independent invasion by C5a peptidase into epithelial cells in group A Streptococcus

Background & objectives: Group A Streptococcus, causative agent of several clinical manifestations codes for multiple protein invasins which help the bacterium to enter non-phagocytic cells. C5a peptidase (SCPA) is a surface protein conserved among different serotypes of M1 strain. The present study was taken up to study SCPA promoted fibronectin independent entry of GAS into epithelial cells. Methods: An isogenic 90226 emm1DeltaAB (M1(-)) mutant was constructed, with thermosensitive pGhost vector. This isogenic M1(-) mutant expressed SCPA on the surface as determined by Western blotting and immunofluorescence. Results: On preincubation with anti-SCPA serum, the isogenic M1(-) strain exhibited 54 per cent decreased invasion as compared to the bacteria incubated with control serum. Also, purified recombinant SCPA proteins blocked internalization of M1(-) streptococci into HEp-2 cells. The M1(-) strain invaded at the same efficiency in the presence or absence of fibronectin. Interpretation & conclusion: These results suggested that SCPA acted as a potential invasin of group A streptococcus and promoted invasion independent of fibronectin.

Disease burden due to Streptococcus dysgalactiae subsp equisimilis (group G and C streptococcus) is higher than that due to Streptococcus pyogenes among Mumbai school children

Streptococcus pyogenes [group A streptococcus (GAS)], a human pathogen, and Streptococcus dysgalactiae subsp. equisimilis [human group G and C streptococcus (GGS/GCS)] are evolutionarily related, share the same tissue niche in humans, exchange genetic material, share up to half of their virulence-associated genes and cause a similar spectrum of diseases. Yet, GGS/GCS is often considered as a commensal bacterium and its role in streptococcal disease burden is under-recognized. While reports of the recovery of GGS/GCS from normally sterile sites are increasing, studies describing GGS/GCS throat colonization rates relative to GAS in the same population are very few. This study was carried out in India where the burden of streptococcal diseases, including rheumatic fever and rheumatic heart disease, is high. As part of a surveillance study, throat swabs were taken from 1504 children attending 7 municipal schools in Mumbai, India, during 2006-2008. GAS and GGS/GCS were identified on the basis of beta-haemolytic activity, carbohydrate group and PYR test, and were subsequently typed. The GGS/GCS carriage rate (1166/1504, 11%) was eightfold higher than the GAS carriage (22/1504, 1.5%) rate in this population. The 166 GGS/GCS isolates collected represented 21 different emm types (molecular types), and the 22 GAS isolates represented 15 different emm types. Although the rate of pharyngitis associated with GGS/GCS is marginally lower than with GAS, high rates of throat colonization by GGS/GCS underscore its importance in the pathogenesis of pharyngitis.

Role of predictors in downscaling surface temperature to river basin in India for IPCC SRES scenarios using support vector machine

In this paper, downscaling models are developed using a support vector machine (SVM) for obtaining projections of monthly mean maximum and minimum temperatures (T-max and T-min) to river-basin scale. The effectiveness of the model is demonstrated through application to downscale the predictands for the catchment of the Malaprabha reservoir in India, which is considered to be a climatically sensitive region. The probable predictor variables are extracted from (1) the National Centers for Environmental Prediction (NCEP) reanalysis dataset for the period 1978-2000, and (2) the simulations from the third-generation Canadian Coupled Global Climate Model (CGCM3) for emission scenarios A1B, A2, B1 and COMMIT for the period 1978-2100. The predictor variables are classified into three groups, namely A, B and C. Large-scale atmospheric variables Such as air temperature, zonal and meridional wind velocities at 925 nib which are often used for downscaling temperature are considered as predictors in Group A. Surface flux variables such as latent heat (LH), sensible heat, shortwave radiation and longwave radiation fluxes, which control temperature of the Earth's surface are tried as plausible predictors in Group B. Group C comprises of all the predictor variables in both the Groups A and B. The scatter plots and cross-correlations are used for verifying the reliability of the simulation of the predictor variables by the CGCM3 and to Study the predictor-predictand relationships. The impact of trend in predictor variables on downscaled temperature was studied. The predictor, air temperature at 925 mb showed an increasing trend, while the rest of the predictors showed no trend. The performance of the SVM models that are developed, one for each combination of predictor group, predictand, calibration period and location-based stratification (land, land and ocean) of climate variables, was evaluated. In general, the models which use predictor variables pertaining to land surface improved the performance of SVM models for downscaling T-max and T-min

Random existence of charge ordered stripes and its influence on the magnetotransport properties of La0.6Sr0.4MnO3 perovskite substituted with diamagnetic ions at Mn sublattice

Phase-singular solid solutions of La0.6Sr0.4Mn1-yMeyO3 (0 <= y <= 0.3) [Me=Li1+, Mg2+, Al3+, Ti4+, Nb5+, Mo6+ or W6+] [LSMey] perovskite of rhombohedral symmetry (space group: R (3) over barc) have been prepared wherein the valence of the diamagnetic substituent at Mn site ranged from 1 to 6. With increasing y-content in LSMey, the metal-insulator (TM-I) transition in resistivity-temperature rho(T) curves shifted to low temperatures. The magnetization studies M(H) as well as the M(T) indicated two groups for LSMey. (1) Group A with Me=Mg, Al, Ti, or Nb which are paramagnetic insulators (PIs) at room temperature with low values of M (< 0.5 mu(B)/Mn); the magnetic transition [ferromagnetic insulator (FMI)-PI] temperature (T-C) shifts to low temperatures and nearly coincides with that of TM-I and the maximum magnetoresistance (MR) of similar to 50% prevails near T-C (approximate to TM-I). (2) Group-B samples with Me=Li, Mo, or W which are FMIs with M-s=3.3-3.58 mu(B)/Mn and marginal reduction in T-C similar to 350 K as compared to the undoped LSMO (T-C similar to 378 K). The latter samples show large temperature differences Delta T=T-c-TM-I, reaching up to similar to 288 K. The maximum MR (similar to 60%) prevails at low temperatures corresponding to the M-I transition TM-I rather than around T-C. High resolution lattice images as well as microscopy analysis revealed the prevalence of inhomogeneous phase mixtures of randomly distributed charge ordered-insulating (COI) bistripes (similar to 3-5 nm width) within FMI charge-disordered regions, yet maintaining crystallographically single phase with no secondary precipitate formation. The averaged ionic radius < r(B)>, valency, or charge/radius ratio < CRR > cannot be correlated with that of large Delta T; hence cannot be used to parametrize the discrepancy between T-C and TM-I. The M-I transition is controlled by the charge conduction within the electronically heterogeneous mixtures (COI bistripes+FMI charge disordered); large MR at TM-I suggests that the spin-ordered FM-insulating regions assist the charge transport, whereas the T-C is associated with the bulk spin ordered regions corresponding to the FMI phase of higher volume fraction of which anchors the T-C to higher temperatures. The present analysis showed that the double-exchange model alone cannot account for the wide bifurcation of the magnetic and electric transitions, contributions from the charge as well as lattice degrees of freedom to be separated from spin/orbital ordering. The heterogeneous phase mixtures (COI+FMI) cannot be treated as of granular composite behavior. (c) 2008 American Institute of Physics.

B Physics: WHEPP-XI working group report

We present the report of the B physics working group of the Workshop on High Energy Physics Phenomenology (WHEPP-XI), held at the Physical Research Laboratory, Ahmedabad, in January 2010.

Crystallization and preliminary X-ray diffraction studies of sortase A from Streptococcus pneumoniae

Sortases are cell-membrane-anchored cysteine transpeptidases that are essential for the assembly and anchoring of cell-surface adhesins in Gram-positive bacteria. Thus, they play critical roles in virulence, infection and colonization by pathogens. Sortases have been classified into four types based on their primary sequence and the target-protein motifs that they recognize. All Gram-positive bacteria express a class A housekeeping sortase (SrtA). Sortase A from Streptococcus pneumoniae (NP_358691) has been crystallized in two crystal forms. Diamond-shaped crystals of Delta N(59)SrtA diffracted to 4.0 angstrom resolution and belonged to a tetragonal system with unit-cell parameters a = b = 122.8, c = 86.5 angstrom, alpha = beta = gamma = 90 degrees, while rod-shaped crystals of Delta N(81)SrtA diffracted to 2.91 angstrom resolution and belonged to the monoclinic space group P2(1) with unit-cell parameters a = 66.8, b = 103.47, c = 74.79 angstrom, alpha = gamma = 90, beta = 115.65 degrees. The Matthews coefficient (V(M) = 2.77 angstrom(3) Da(-1)) with similar to 56% solvent content suggested the presence of four molecules in the asymmetric unit for Delta N(81)SrtA. Also, a multi-copy search using a monomer as a probe in the molecular-replacement method resulted in the successful location of four sortase molecules in the asymmetric unit, with statistics R = 41.61, R(free) = 46.44, correlation coefficient (CC) = 64.31, CC(free) = 57.67.

Working group report: Dictionary of Large Hadron Collider signatures

We report on a plan to establish a `Dictionary of LHC Signatures', an initiative that started at the WHEPP-X workshop in Chennai, January 2008. This study aims at the strategy of distinguishing 3 classes of dark matter motivated scenarios such as R-parity conserved supersymmetry, little Higgs models with T-parity conservation and universal extra dimensions with KK-parity for generic cases of their realization in a wide range of the model space. Discriminating signatures are tabulated and will need a further detailed analysis.

Systematic stability analysis of the renormalization group flow for the normal-superconductor-normal junction of Luttinger liquid wires

We study the renormalization group flows of the two terminal conductance of a superconducting junction of two Luttinger liquid wires. We compute the power laws associated with the renormalization group flow around the various fixed points of this system using the generators of the SU(4) group to generate the appropriate parametrization of an matrix representing small deviations from a given fixed point matrix [obtained earlier in S. Das, S. Rao, and A. Saha, Phys. Rev. B 77, 155418 (2008)], and we then perform a comprehensive stability analysis. In particular, for the nontrivial fixed point which has intermediate values of transmission, reflection, Andreev reflection, and crossed Andreev reflection, we show that there are eleven independent directions in which the system can be perturbed, which are relevant or irrelevant, and five directions which are marginal. We obtain power laws associated with these relevant and irrelevant perturbations. Unlike the case of the two-wire charge-conserving junction, here we show that there are power laws which are nonlinear functions of V(0) and V(2kF) [where V(k) represents the Fourier transform of the interelectron interaction potential at momentum k]. We also obtain the power law dependence of linear response conductance on voltage bias or temperature around this fixed point.

Gauge theory of a group of diffeomorphisms. I. General principles

Any (N+M)-parameter Lie group G with an N-parameter subgroup H can be realized as a global group of diffeomorphisms on an M-dimensional base space B, with representations in terms of transformation laws of fields on B belonging to linear representations of H. The gauged generalization of the global diffeomorphisms consists of general diffeomorphisms (or coordinate transformations) on a base space together with a local action of H on the fields. The particular applications of the scheme to space-time symmetries is discussed in terms of Lagrangians, field equations, currents, and source identities. Journal of Mathematical Physics is copyrighted by The American Institute of Physics.

Beta-Ketoacyl-ACP Synthase I/II from Plasmodium falciparum (PfFabB/F)-Is it B or F?

Condensing enzymes play an important and decisive role in terms of fatty acid composition of any organism. They can be classified as condensing enzymes involved in initiating the cycle and enzymes involved in elongating the initiated fatty acyl chain. In E. coli, two isoforms for the elongation condensing enzymes (FabB and FabF) exists whereas Plasmodium genome contains only one isoform. By in vitro complementation studies in E. coli CY244 cells, we show that PfFabB/ functions like E. coli FabF as the growth of the mutant cells could rescued only in the presence of oleic acid. But unlike bacterial enzyme, PfFabB/F does not increase the cis-vaccenic acid content in the mutant cells upon lowering the growth temperature. This study thus highlights the distinct properties of P. falciparum FabF which sets it apart from E. coli and most other enzymes of this family, described so far.

Structure of (4S)-2,4-dimethyl-1,2-dihydropyrazino[2,1-b]quinazoline-3(4H),6-dione

C13HI3N302, orthorhombic, P2~2121, a = 17.443 (5), b = 11.650 (4), c = 5.784 (1)/~, Z = 4, d m = 1.456, d c = 1.429 Mg m -3, F(000) = 512, g(Cu Ka) = 0.843 mm-L The R index is 0.040 for 1358 significant reflections. The structure is stabilized by C-H...O interactions. The N-methylated eis peptide group which forms part of a six-membered ring is non-planar. The torsion angle about the peptide bond is -6.1 (4) ° and the peptide bond length is 1.337 (3) A.

Sequence dependence and role of 5'-phosphate in the B to Z transition

Spectroscopic studies on pd(CG)3 and pd(GC)3 have been carried out to elucidate the sequence dependence and effect of free 5'-phosphate on the B to Z transition. Unlike d(CG)3, pd(CG)3 fails to undergo salt-induced B to Z transition at ambient temperature. Model building studies have been carried out to determine the inhibitory role of the 5'-phosphate group, but have been unsuccessful.

Structure of (4S)-2,4-dimethyl-1,2-dihydropyrazino[2,1-b]quinazoline-3(4H),6-dione

C13HI3N302, orthorhombic, P2~2121, a = 17.443 (5), b = 11.650 (4), c = 5.784 (1)/~, Z = 4, d m = 1.456, d c = 1.429 Mg m -3, F(000) = 512, g(Cu Ka) = 0.843 mm-L The R index is 0.040 for 1358 significant reflections. The structure is stabilized by C-H...O interactions. The N-methylated eis peptide group which forms part of a six-membered ring is non-planar. The torsion angle about the peptide bond is -6.1 (4) ° and the peptide bond length is 1.337 (3) A.

Electron energy distributions and transport coefficients in N2 in E times B fields

Using the concept of energy-dependent effective field intensity, electron transport coefficients in nitrogen have been determined in E times B fields (E = electric field intensity, B = magnetic flux density) by the numerical solution of the Boltzmann transport equation for the energy distribution of electrons. It has been observed that as the value of B/p (p = gas pressure) is increased from zero, the perpendicular drift velocity increased linearly at first, reaches a maximum value, and then decreases with increasing B/p. In general, the electron mean energy is found to be a function of Eavet/p( Eavet = averaged effective electric field intensity) only, but the other transport coefficients, such as transverse drift velocity, perpendicular drift velocity, and the Townsend ionization coefficient, are functions of both E/p and B/p.

Ligand Specificity of Group I Biotin Protein Ligase of Mycobacterium tuberculosis

Background: Fatty acids are indispensable constituents of mycolic acids that impart toughness & permeability barrier to the cell envelope of M. tuberculosis. Biotin is an essential co-factor for acetyl-CoA carboxylase (ACC) the enzyme involved in the synthesis of malonyl-CoA, a committed precursor, needed for fatty acid synthesis. Biotin carboxyl carrier protein (BCCP) provides the co-factor for catalytic activity of ACC. Methodology/Principal Findings: BPL/BirA (Biotin Protein Ligase), and its substrate, biotin carboxyl carrier protein (BCCP) of Mycobacterium tuberculosis (Mt) were cloned and expressed in E. coli BL21. In contrast to EcBirA and PhBPL, the similar to 29.5 kDa MtBPL exists as a monomer in native, biotin and bio-5'AMP liganded forms. This was confirmed by molecular weigt profiling by gel filtration on Superdex S-200 and Dynamic Light Scattering (DLS). Computational docking of biotin and bio-5'AMP to MtBPL show that adenylation alters the contact residues for biotin. MtBPL forms 11 H-bonds with biotin, relative to 35 with bio-5'AMP. Docking simulations also suggest that bio-5'AMP hydrogen bonds to the conserved `GRGRRG' sequence but not biotin. The enzyme catalyzed transfer of biotin to BCCP was confirmed by incorporation of radioactive biotin and by Avidin blot. The K-m for BCCP was similar to 5.2 mu M and similar to 420 nM for biotin. MtBPL has low affinity (K-b = 1.06 x 10(-6) M) for biotin relative to EcBirA but their K-m are almost comparable suggesting that while the major function of MtBPL is biotinylation of BCCP, tight binding of biotin/bio-5'AMP by EcBirA is channeled for its repressor activity. Conclusions/Significance: These studies thus open up avenues for understanding the unique features of MtBPL and the role it plays in biotin utilization in M. tuberculosis.