Analysis of DevR regulated genes in Mycobacterium tuberculosis

The DevRS two component system of Mycobacterium tuberculosis is responsible for its dormancy in host and becomes operative under hypoxic condition. It is experimentally known that phosphorylated DevR controls the expression of several downstream genes in a complex manner. In the present work we propose a theoretical model to show role of binding sites in DevR mediated gene expression. Individual and collective role of binding sites in regulating DevR mediated gene expression has been shown via modeling. Objective of the present work is twofold. First, to describe qualitatively the temporal dynamics of wild type genes and their known mutants. Based on these results we propose that DevR controlled gene expression follows a specific pattern which is efficient in describing other DevR mediated gene expression. Second, to analyze behavior of the system from information theoretical point of view. Using the tools of information theory we have calculated molecular efficiency of the system and have shown that it is close to the maximum limit of isothermal efficiency.     

Synthesis of HPMC stabilized nickel nanoparticles and investigation of their magnetic and catalytic properties

Nickel nanoparticles synthesized from NiCl₂·6H₂O by hydrazine hydrate in mixed solvent of ethanol and water in the presence of hydroxypropylmethylcellulose (HPMC) as protective and stabilizing agents. The morphology and sizes of synthesized Ni nanoparticles were studied by field-emission-scanning-electron microscopy (FESEM). Structural properties of nanoparticles were examined by X-ray diffraction (XRD). The polymer stabilized Ni nanoparticles were characterized by Fourier-transform infrared (FTIR) spectroscopy. The magnetic measurement showed that the resultant Ni nanoparticles were ferromagnetic. Also, the saturation magnetization (M_S), remanent magnetization (M_R) and coercivity (M_R) were observed to increase with decreasing temperature. The results of magnetic characterization showed that the magnetic properties of the HPMC stabilized Ni nanoparticles are quite different from those of the bared Ni nanoparticles. All the observed magnetic properties essentially reflected the very typical nanoparticle type nature. Consequently, the resulting Ni nanoparticles were found to be highly active and recyclable catalyst for Suzuki coupling reactions.     

Daphne thanguensis sp. nov. (Thymelaeaceae) from Sikkim Himalaya

Daphne thanguensis sp. nov. from north Sikkim of eastern Himalaya is described and illustrated. It is a narrow endemic related to D. tangutica Maxim. Daphne thanguensis grows in open alpine pastures and differs from D. tangutica by having leaves with revolute margin and a tuft of hairs at apex, ebracteate inflorescence and flowers, calyx lobes with a tuft of hairs at apex and annular, slightly undulate hypogynal disk. The new taxon is also close to D. retusa Hemsl. But can easily be differentiated by its sessile inflorescence, ebracteate flowers and tuft of hairs at leaf apices and calyx lobe apices. A conservation status of the new species in accordance with the IUCN red list categories and criteria is provided and discussed.     

Insights into the Substrate Specificity of a Thioesterase Rv0098 of Mycobacterium Tuberculosis through X-ray Crystallographic and Molecular Dynamics Studies

Abstract

The crystal structure of Rv0098, a long-chain fatty acyl-CoA thioesterase from Mycobacterium tuberculosis with bound dodecanoic acid at the active site provided insights into the mode of substrate binding but did not reveal the structural basis of substrate specificities of varying chain length. Molecular dynamics studies demonstrated that certain residues of the substrate binding tunnel are flexible and thus modulate the length of the tunnel. The flexibility of the loop at the base of the tunnel was also found to be important for determining the length of the tunnel for accommodating appropriate substrates. A combination of crystallographic and molecular dynamics studies thus explained the structural basis of accommodating long chain substrates by Rv0098 of M. tuberculosis.     

Association of Vitamin B12, Lactate Dehydrogenase,and Regulation of NF-κB in the Mitigation of Sodium Arsenite-Induced ROS Generation in Uterine Tissue by Commercially Available Probiotics

Probiotics and Antimicrobial Proteins - Managing arsenic intoxication with conventional metal chelators is a global challenge. The present study demonstrated the therapeutic role of probiotics...     

Molecular characterization and localization of Plasmodium falciparum choline kinase

Generation of phosphocholine by choline kinase is important for phosphatidylcholine biosynthesis via Kennedy pathway and phosphatidylcholine biosynthesis is essential for intraerythrocytic growth of malaria parasite. A putative gene (Gene ID PF14_0020) in chromosome 14, having highest sequence homology with choline kinase, has been identified by BLAST searches from P. falciparum genome sequence database. This gene has been PCR amplified, cloned, over-expressed and characterized. Choline kinase activity of the recombinant protein (PfCK) was validated as it catalyzed the formation of phosphocholine from choline in presence of ATP. The K_m values for choline and ATP are found to be 145 ± 20 μM and 2.5 ± 0.3 mM, respectively. PfCK can phosphorylate choline efficiently but not ethanolamine. Southern blotting indicates that PfCK is a single copy gene and it is a cytosolic protein as evidenced by Western immunoblotting and confocal microscopy. A model structure of PfCK was constructed based on the crystal structure of choline kinase of C. elegans to search the structural homology. Consistent with the homology modeling predictions, CD analysis indicates that the α and β content of PfCK are 33% and 14%, respectively. Since choline kinase plays a vital role for growth and multiplication of P. falciparum during intraerythrocytic stages, we can suggest that this well characterized PfCK may be exploited in the screening of new choline kinase inhibitors to evaluate their antimalarial activity.     

Glucans of Pleurotus florida blue variant: isolation, purification, characterization and immunological studies

Two different glucans (PS-I and PS-II) were isolated from the alkaline extract of the fruiting bodies of an edible mushroom, Pleurotus florida blue variant and the PS-I showed macrophage, splenocyte and thymocyte activations. On the basis of sugar analysis, methylation analysis, periodate oxidation, and NMR studies ((1)H, (13)C, DEPT-135, DQF-COSY, TOCSY, NOESY, ROESY, HMQC and HMBC), the structure of the repeating unit of these polysaccharides were established.     

Acivicin with glutaminase regulates proliferation and invasion of human MCF-7 and OAW-42 cells--an in vitro study

Tumor cells intensely utilize glutamine as the major source of respiratory fuel. Glutamine-analogue acivicin inhibits tumor growth and tumor-induced angiogenesis in Ehrlich ascites carcinoma. In the present study, antitumor properties of acivicin in combination with glutaminase enzyme is reported. Acivicin along with E. coli glutaminase synergistically reduced in vitro proliferation and matrigel invasion of human MCF-7 and OAW-42 cells. Effects of single and combined treatments with acivicin and glutaminase on angiogenic factors were also analyzed in these cell lines. Co-administration of the treatment agents inhibits the release of VEGF and MMP-9 by cells in culture supernatant significantly than single agent treatments. The result suggests that combination of acivicin with glutaminase may provide a better therapeutic option than either of them given separately for treating human breast and ovarian cancer. However, further studies are required to be conducted in vivo for its confirmation.     

Indomethacin inactivates gastric peroxidase to induce reactive-oxygen-mediated gastric mucosal injury and curcumin protects it by preventing peroxidase inactivation and scavenging reactive oxygen

We have investigated the mechanism of indomethacin-induced gastric ulcer caused by reactive oxygen species (ROS) and the gastroprotective effect of curcumin thereon. Curcumin dose-dependently blocks indomethacin-induced gastric lesions, showing 82% protection at 25 mg/kg. Indomethacin-induced oxidative damage by ROS as shown by increased lipid peroxidation and thiol depletion is almost completely blocked by curcumin. Indomethacin causes nearly fivefold increase in hydroxyl radical (()OH) and significant inactivation of gastric mucosal peroxidase to elevate endogenous H(2)O(2) and H(2)O(2)-derived ()OH, which is prevented by curcumin. In vitro studies indicate that indomethacin inactivates peroxidase irreversibly only in presence of H(2)O(2) by acting as a suicidal substrate. 5,5-Dimethyl-pyrroline-N-oxide (DMPO) protects the peroxidase, indicating involvement of indomethacin radical in the inactivation. Indomethacin radical was also detected in the peroxidase-indomethacin-H(2)O(2) system as DMPO adduct (a(N) = 15 G, a(beta)(H) = 16 G) by electron spin resonance spectroscopy. Curcumin protects the peroxidase in a concentration-dependent manner and consumes H(2)O(2) for its oxidation as a suitable substrate of the peroxidase, thereby blocking indomethacin oxidation. Curcumin can also scavenge ()OH in vitro. We suggest that curcumin protects gastric damage by efficient removal of H(2)O(2) and H(2)O(2) -derived ()OH by preventing peroxidase inactivation by indomethacin.