Structural Annotation of Mycobacterium tuberculosis Proteome

Of the similar to 4000 ORFs identified through the genome sequence of Mycobacterium tuberculosis (TB) H37Rv, experimentally determined structures are available for 312. Since knowledge of protein structures is essential to obtain a high-resolution understanding of the underlying biology, we seek to obtain a structural annotation for the genome, using computational methods. Structural models were obtained and validated for similar to 2877 ORFs, covering similar to 70% of the genome. Functional annotation of each protein was based on fold-based functional assignments and a novel binding site based ligand association. New algorithms for binding site detection and genome scale binding site comparison at the structural level, recently reported from the laboratory, were utilized. Besides these, the annotation covers detection of various sequence and sub-structural motifs and quaternary structure predictions based on the corresponding templates. The study provides an opportunity to obtain a global perspective of the fold distribution in the genome. The annotation indicates that cellular metabolism can be achieved with only 219 folds. New insights about the folds that predominate in the genome, as well as the fold-combinations that make up multi-domain proteins are also obtained. 1728 binding pockets have been associated with ligands through binding site identification and sub-structure similarity analyses. The resource (http://proline.physics.iisc.ernet.in/Tbstructuralannotation), being one of the first to be based on structure-derived functional annotations at a genome scale, is expected to be useful for better understanding of TB and for application in drug discovery. The reported annotation pipeline is fairly generic and can be applied to other genomes as well.

Thermodynamic properties of Pt5La, Pt5Ce, Pt5Pr, Pt5Tb and Pt5Tm intermetallics

The Gibbs’ energies of formation of Pt5La, Pt5Ce, Pt5Pr, Pt5Tb and Pt5 Tm intermetallic compounds have been determined in the temperature range 870–1100 K using the solid state cell:Ta,M + MF3 /CaF2 /Pt5 M + Pt + MF3 ,TaTaM+MF3CaF2Pt5M+Pt+MF3Ta.The reversible emf of the cell is directly related to the Gibbs’ energy of formation of the Pt5M compound. The results can be summarized by the equations:DGf° á Pt5 La ñ = - 373,150 + 6 ·60 T( ±300 )J mol - 1 DGf° á Pt5 Ce ñ = - 367,070 + 5 ·79 T( ±300 )J mol - 1 DGf° á Pt5 Pr ñ = - 370,540 + 4 ·69 T( ±300 )J mol - 1 DGf° á Pt5 Tb ñ = - 372,280 + 4 ·11 T( ±300 )J mol - 1 DGf° á Pt5 Tm ñ = - 368,230 + 4 ·89 T( ±300 )J mol - 1 Unknown control sequence '\hfill'relative to the low temperature allotropic form of the lanthanide element and solid platinum as standard states The enthalpies of formation of all the Pt5M intermetallic compounds obtained in this study are in good agreement with Miedema’s model. The experimental values are more negative than those calculated using the model. The variation of the thermodynamic properties of Pt5M compounds with atomic number of the lanthanide element is discussed in relation to valence state and molar volume.

Study of surface oxidation of rare-earth-metals by photoelectron-spectroscopy

Surface oxidation of La, Ce, Sm and Tb metals has been investigated by He(II) ultraviolet photoelectron spectroscopy (u.p.s.) and X-ray photoelectron spectroscopy (X.p.s.). Oxidation of La gives rise to La2O3 on the surface. While Ce2O3 appears to be the stable oxide on the surface, we find evidence for formation of CeO2 at high oxygen exposure. Valence band of Sm clearly shows the presence of both divalent and trivalent states due to interconfigurational fluctuation. Exposure of Sm to oxygen first depletes the divalent Sm at the surface. While Sm2O3 is the stable oxide on the surface of Sm, Tb2O3 is the stable oxide on the surface of Tb (and not any of the higher oxides).

Pattern recognition and cellular immune responses to novel Mycobacterium tuberculosis-antigens in individuals from Belarus

Background: Tuberculosis (TB) is an enduring health problem worldwide and the emerging threat of multidrug resistant (MDR) TB and extensively drug resistant (XDR) TB is of particular concern. A better understanding of biomarkers associated with TB will aid to guide the development of better targets for TB diagnosis and for the development of improved TB vaccines. Methods: Recombinant proteins (n = 7) and peptide pools (n = 14) from M. tuberculosis (M.tb) antigens associated with M.tb pathogenicity, modification of cell lipids or cellular metabolism, were used to compare T cell immune responses defined by IFN-gamma production using a whole blood assay (WBA) from i) patients with TB, ii) individuals recovered from TB and iii) individuals exposed to TB without evidence of clinical TB infection from Minsk, Belarus. Results: We identified differences in M.tb target peptide recognition between the test groups, i.e. a frequent recognition of antigens associated with lipid metabolism, e.g. cyclopropane fatty acyl phospholipid synthase. The pattern of peptide recognition was broader in blood from healthy individuals and those recovered from TB as compared to individuals suffering from pulmonary TB. Detection of biologically relevant M.tb targets was confirmed by staining for intracellular cytokines (IL-2, TNF-alpha and IFN-gamma) in T cells from non-human primates (NHPs) after BCG vaccination. Conclusions: PBMCs from healthy individuals and those recovered from TB recognized a broader spectrum of M.tb antigens as compared to patients with TB. The nature of the pattern recognition of a broad panel of M.tb antigens will devise better strategies to identify improved diagnostics gauging previous exposure to M.tb; it may also guide the development of improved TB-vaccines.

Phase relationships and magnetic properties of TbxDy1-xFe1.95 alloys

The effect of Tb/Dy ratio on the structural and magnetic properties of (Tb,Dy)Fe-2 class of alloys has been investigated using nine alloys of TbxDy1-xFe1.95 (x = 0-1) covering the entire range. Our results indicate that the three phases viz. (Tb,Dy)Fe-2 (major phase), (Tb,Dy)Fe-3 and(Tb,Dy)-solid solution (minor phases) coexist in all the alloys. The volume fraction of pro-peritectic (Tb,Dy)Fe-3 phase however, has a minimum at x = 0.4 and a maximum at x = 0.6 compositions. The volume fraction of this phase decreases upon heat treatment at 850 degrees C and 1000 degrees C. A Widmanstatten type precipitate of (Tb,Dy)Fe-3 was observed for Dy-rich compositions (0 <= x <= 0.5). The microstructural investigations indicate that the ternary phase equilibria of Tb-Dy-Fe are sensitive to Tb/Dy ratio including the expansion of (Tb,Dy)Fe-2 phase field which is in contrast to the pseudo-binary assumption that is followed in available literature to date. The lattice parameter, Curie temperature and coercivity are found to increase with Tb addition. Split of (440) peak of (Tb,Dy)Fe-2 observed in x >= 0.3 alloys indicate, a spin reorientation transition from 100] to 111] occurs with Tb addition. (C) 2012 Elsevier B. V. All rights reserved.

Highly luminescent and thermally stable lanthanide coordination polymers designed from 4-(dipyridin-2-yl)aminobenzoate: efficient energy transfer from Tb3+ to Eu3+ in a mixed lanthanide coordination compound

Herein, a new aromatic carboxylate ligand, namely, 4-(dipyridin-2-yl)aminobenzoic acid (HL), has been designed and employed for the construction of a series of lanthanide complexes (Eu3+ = 1, Tb3+ = 2, and Gd3+ = 3). Complexes of 1 and 2 were structurally authenticated by single-crystal X-ray diffraction and were found to exist as infinite 1D coordination polymers with the general formulas {Eu(L)(3)(H2O)(2)]}(n) (1) and {Tb(L)(3)(H2O)]center dot(H2O)}(n) (2). Both compounds crystallize in monoclinic space group C2/c. The photophysical properties demonstrated that the developed 4-(dipyridin-2-yl)aminobenzoate ligand is well suited for the sensitization of Tb3+ emission (Phi(overall) = 64%) thanks to the favorable position of the triplet state ((3)pi pi*) of the ligand the energy difference between the triplet state of the ligand and the excited state of Tb3+ (Delta E) = (3)pi pi* - D-5(4) = 3197 cm(-1)], as investigated in the Gd3+ complex. On the other hand, the corresponding Eu3+ complex shows weak luminescence efficiency (Phi(overall) = 7%) due to poor matching of the triplet state of the ligand with that of the emissive excited states of the metal ion (Delta E = (3)pi pi* - D-5(0) = 6447 cm(-1)). Furthermore, in the present work, a mixed lanthanide system featuring Eu3+ and Tb3+ ions with the general formula {Eu0.5Tb0.5(L)(3)(H2O)(2)]}(n) (4) was also synthesized, and the luminescent properties were evaluated and compared with those of the analogous single-lanthanide-ion systems (1 and 2). The lifetime measurements for 4 strongly support the premise that efficient energy transfer occurs between Tb3+ and Eu3+ in a mixed lanthanide system (eta = 86%).

Bubble size measurement and error analysis in a gas liquid ejector

Bubble size in a gas liquid ejector has been measured using the image technique and analysed for estimation of Sauter mean diameter. The individual bubble diameter is estimated by considering the two dimensional contour of the ellipse, for the actual three dimensional ellipsoid in the system by equating the volume of the ellipsoid to that of the sphere. It is observed that the bubbles are of oblate and prolate shaped ellipsoid in this air water system. The bubble diameter is calculated based on this concept and the Sauter mean diameter is estimated. The error between these considerations is reported. The bubble size at different locations from the nozzle of the ejector is presented along with their percentage error which is around 18%.

Hydrodynamics of soft active matter

This review summarizes theoretical progress in the field of active matter, placing it in the context of recent experiments. This approach offers a unified framework for the mechanical and statistical properties of living matter: biofilaments and molecular motors in vitro or in vivo, collections of motile microorganisms, animal flocks, and chemical or mechanical imitations. A major goal of this review is to integrate several approaches proposed in the literature, from semimicroscopic to phenomenological. In particular, first considered are ``dry'' systems, defined as those where momentum is not conserved due to friction with a substrate or an embedding porous medium. The differences and similarities between two types of orientationally ordered states, the nematic and the polar, are clarified. Next, the active hydrodynamics of suspensions or ``wet'' systems is discussed and the relation with and difference from the dry case, as well as various large-scale instabilities of these nonequilibrium states of matter, are highlighted. Further highlighted are various large-scale instabilities of these nonequilibrium states of matter. Various semimicroscopic derivations of the continuum theory are discussed and connected, highlighting the unifying and generic nature of the continuum model. Throughout the review, the experimental relevance of these theories for describing bacterial swarms and suspensions, the cytoskeleton of living cells, and vibrated granular material is discussed. Promising extensions toward greater realism in specific contexts from cell biology to animal behavior are suggested, and remarks are given on some exotic active-matter analogs. Last, the outlook for a quantitative understanding of active matter, through the interplay of detailed theory with controlled experiments on simplified systems, with living or artificial constituents, is summarized.

Design and synthesis of positional isomers of 5 and 6-bromo-1-(phenyl)sulfonyl]-2-(4-nitrophenoxy)methyl]-1H-benzimida zoles as possible antimicrobial and antitubercular agents

In this Letter, we report the structure activity relationship (SAR) studies on series of positional isomers of 5(6)-bromo-1-(phenyl)sulfonyl]-2-(4-nitrophenoxy)methyl]-1H-benzim idazoles derivatives 7(a-j) and 8(a j) synthesized in good yields and characterized by H-1 NMR, C-13 NMR and mass spectral analyses. The crystal structure of 7a was evidenced by X-ray diffraction study. The newly synthesized compounds were evaluated for their in vitro antibacterial activity against Staphylococcus aureus, (Gram-positive), Escherichia coil and Klebsiella pneumoniae (Gram-negative), antifungal activity against Candida albicans, Aspergillus flavus and Rhizopus sp. and antitubercular activity against Mycobacterium tuberculosis H37Rv, Mycobacterium smegmatis, Mycobacterium fortuitum and MDR-TB strains. The synthesized compounds displayed interesting antimicrobial activity. The compounds 7b, 7e and 7h displayed significant activity against Mycobacterium tuberculosis H37Rv strain.

Copula-Based Modeling of TMI Brightness Temperature With Rainfall Type

Overland rain retrieval using spaceborne microwave radiometer offers a myriad of complications as land presents itself as a radiometrically warm and highly variable background. Hence, land rainfall algorithms of the Tropical Rainfall Measuring Mission (TRMM) Microwave Imager (TMI) have traditionally incorporated empirical relations of microwave brightness temperature (Tb) with rain rate, rather than relying on physically based radiative transfer modeling of rainfall (as implemented in the TMI ocean algorithm). In this paper, sensitivity analysis is conducted using the Spearman rank correlation coefficient as benchmark, to estimate the best combination of TMI low-frequency channels that are highly sensitive to the near surface rainfall rate from the TRMM Precipitation Radar (PR). Results indicate that the TMI channel combinations not only contain information about rainfall wherein liquid water drops are the dominant hydrometeors but also aid in surface noise reduction over a predominantly vegetative land surface background. Furthermore, the variations of rainfall signature in these channel combinations are not understood properly due to their inherent uncertainties and highly nonlinear relationship with rainfall. Copula theory is a powerful tool to characterize the dependence between complex hydrological variables as well as aid in uncertainty modeling by ensemble generation. Hence, this paper proposes a regional model using Archimedean copulas, to study the dependence of TMI channel combinations with respect to precipitation, over the land regions of Mahanadi basin, India, using version 7 orbital data from the passive and active sensors on board TRMM, namely, TMI and PR. Studies conducted for different rainfall regimes over the study area show the suitability of Clayton and Gumbel copulas for modeling convective and stratiform rainfall types for the majority of the intraseasonal months. Furthermore, large ensembles of TMI Tb (from the most sensitive TMI channel combination) were generated conditional on various quantiles (25th, 50th, 75th, and 95th) of the convective and the stratiform rainfall. Comparatively greater ambiguity was observed to model extreme values of the convective rain type. Finally, the efficiency of the proposed model was tested by comparing the results with traditionally employed linear and quadratic models. Results reveal the superior performance of the proposed copula-based technique.

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.

Hetero-tri-spin 2p-3d-4f] Chain Compounds Based on Nitronyl Nitroxide Lanthanide Metallo-Ligands: Synthesis, Structure, and Magnetic Properties

Employing nitronyl nitroxide lanthanide(III) complexes as metallo-ligands allowed the efficient and highly selective preparation of three series of unprecedented heterotri-spin (Cu Ln-radical) one-dimensional compounds. These 2p-3d-4f spin systems, namely Ln(3)Cu(hfac)II(NitPhOAII)41 (Ln(III)=Gd 1(Gd), Tb 1(Tb), Dy 1(Dy); NitPhOAII=2-(4'-allyloxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3- oxide), Ln(3)Cu(hfac)II(NitPhOPO4] (1-nrn=Gd 2Gd, Tb 2Tb, Dy 2(Dy), Ho 2HOf Yb 2yb; NitPhOPr= 2-(4'-propoxyphenyI)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide) and Ln3Cu(hfac)II(NitPhOB441 (LnIm=Gd 3Gd, Tb 3Tb, Dy 3(Dy); NitPhOBz=2-(4'-benzyloxy- phenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide) involve O-bound nitronyl nitroxide radicals as bridging ligands in chain structures with a Cu-Nit-Ln-Nit-Ln-Nit-Ln-Nit] repeating unit. The dc magnetic studies show that ferromagnetic metal radical interactions take place in these heterotri-spin chain complexes, these and the next-neighbor interactions have been quantified for the Gd derivatives. Complexes 1Tb and 2Tb exhibit frequency dependence of ac magnetic susceptibilities, indicating single-chain magnet behavior.

Optical detection of submicromolar levels of nitro explosives by a submicron sized metal-organic phosphor material

Two isomorphous submicron sized metal-organic network compounds, Y-2(PDA)(3)(H2O)1]center dot 2H(2)O (PDA = 1,4-phenylenediacetate), 1 and Y1.8Tb0.2(PDA)(3)(H2O)1]center dot 2H(2)O, Tb@1 have been synthesized by employing solvent assisted liquid grinding followed by heating at 180 degrees C for 1' min and washing with water. Single crystal X-ray data of bulk 1 confirmed a three dimensional porous structure. The structure and morphology of 1 and Tb@1 were systematically characterized by PXRD, TGA, DSC, IR, SEM and EDX analysis. Dehydrated Tb@1 Tb@1'] shows a high intense visible green emission upon exposure to UV light. The green emission of Tb@1' was used for the detection of nitro explosives, such as 2,4,6-trinitrophenol (TNP), 1,3-dinitro benzene (DNB), 2,4-dinitro toluene (DNT), nitro benzene (NB), and 4-nitro toluene (NT) in acetonitrile. The results show that the emission intensity of dehydrated Tb@1' can be quenched by all the nitro analytes used in the present work. Remarkably, Tb@1' exhibited a high efficiency for TNP, DNB and DNT detection with K-SV K-SV = quenching constant based on linear Stern-Volmer plot] values of 70 920, 44 000 and 35 430 M-1, respectively, which are the highest values amongst known metal-organic materials. Using this material submicromolar level (equivalent to 0.18 ppm), a detection of nitro explosives has been achieved.

Charge density distribution and electrostatic interactions of ethionamide: an inhibitor of the enoyl acyl carrier protein reductase (inhA) enzyme of Mycobacterium tuberculosis

An experimental charge density analysis of an anti-TB drug ethionamide was carried out from high resolution X-ray diffraction at 100 K to understand its charge density distribution and electrostatic properties. The experimental results were validated from periodic theoretical charge density calculations performed using CRYSTAL09 at the B3LYP/6-31G** level of theory. The electron density rho(bcp)(r) and the Laplacian of electron density del(2)(rho bcp)(r) of the molecule calculated from both the methods display the charge density distribution of the ethionamide molecule in the crystal field. The electrostatic potential map shows a large electropositive region around the pyridine ring and a large electronegative region at the vicinity of the thiol atom. The calculated experimental dipole moment is 10.6D, which is higher than the value calculated from theory (8.2D). The topological properties of C-H center dot center dot center dot S, N-H center dot center dot center dot N and N-H center dot center dot center dot S hydrogen bonds were calculated, revealing their strength. The charge density analysis of the ethionamide molecule determined from both the experiment and theory gives the topological and electrostatic properties of the molecule, which allows to precisely understand the nature of intra and intermolecular interactions.

Local spatial structure of forest biomass and its consequences for remote sensing of carbon stocks

Advances in forest carbon mapping have the potential to greatly reduce uncertainties in the global carbon budget and to facilitate effective emissions mitigation strategies such as REDD+ (Reducing Emissions from Deforestation and Forest Degradation). Though broad-scale mapping is based primarily on remote sensing data, the accuracy of resulting forest carbon stock estimates depends critically on the quality of field measurements and calibration procedures. The mismatch in spatial scales between field inventory plots and larger pixels of current and planned remote sensing products for forest biomass mapping is of particular concern, as it has the potential to introduce errors, especially if forest biomass shows strong local spatial variation. Here, we used 30 large (8-50 ha) globally distributed permanent forest plots to quantify the spatial variability in aboveground biomass density (AGBD in Mgha(-1)) at spatial scales ranging from 5 to 250m (0.025-6.25 ha), and to evaluate the implications of this variability for calibrating remote sensing products using simulated remote sensing footprints. We found that local spatial variability in AGBD is large for standard plot sizes, averaging 46.3% for replicate 0.1 ha subplots within a single large plot, and 16.6% for 1 ha subplots. AGBD showed weak spatial autocorrelation at distances of 20-400 m, with autocorrelation higher in sites with higher topographic variability and statistically significant in half of the sites. We further show that when field calibration plots are smaller than the remote sensing pixels, the high local spatial variability in AGBD leads to a substantial ``dilution'' bias in calibration parameters, a bias that cannot be removed with standard statistical methods. Our results suggest that topography should be explicitly accounted for in future sampling strategies and that much care must be taken in designing calibration schemes if remote sensing of forest carbon is to achieve its promise.