Molecular Dynamics Simulation Study and Hybrid Pharmacophore Model Development in Human LTA4H Inhibitor Design

Human leukotriene A4 hydrolase (hLTA4H) is a bi-functional enzyme catalyzes the hydrolase and aminopeptidase functions upon the fatty acid and peptide substrates, respectively, utilizing the same but overlapping binding site. Particularly the hydrolase function of this enzyme catalyzes the rate-limiting step of the leukotriene (LT) cascade that converts the LTA4 to LTB4. This product is a potent pro-inflammatory activator of inflammatory responses and thus blocking this conversion provides a valuable means to design anti-inflammatory agents. Four structurally very similar chemical compounds with highly different inhibitory profile towards the hydrolase function of hLTA4H were selected from the literature. Molecular dynamics (MD) simulations of the complexes of hLTA4H with these inhibitors were performed and the results have provided valuable information explaining the reasons for the differences in their biological activities. Binding mode analysis revealed that the additional thiophene moiety of most active inhibitor helps the pyrrolidine moiety to interact the most important R563 and K565 residues. The hLTA4H complexes with the most active compound and substrate were utilized in the development of hybrid pharmacophore models. These developed pharmacophore models were used in screening chemical databases in order to identify lead candidates to design potent hLTA4H inhibitors. Final evaluation based on molecular docking and electronic parameters has identified three compounds of diverse chemical scaffolds as potential leads to be used in novel and potent hLTA4H inhibitor design

Biomass and carbon stocks of a tropical dry forest of the Javadi Hills, Eastern Ghats, India

Carbon stocks of woody vegetation were assessed in a tropical dry forest of the Javadi Hills at three elevations (high-elevation forest, HEF; mid-elevation forest, MEF; and low-elevation forest, LEF) by laying 15 square plots of 0.25 ha each. All of the adult trees (≥ 30 cm girth at breast height (GBH)), juvenile trees (≥ 10 to < 30 cm GBH) and lianas (≥ 3 cm girth at 1.37 m from the rooting point) were enumerated and woody biomass was assessed by the non-harvest method. The total tree (juvenile + adult tree) aboveground biomass ranged from 99 to 216 Mg/ha. The liana aboveground biomass ranged from 3.6 to 9.3 Mg/ha. The woody vegetation in the present study sites stocked 53 to 116 Mg/ha of carbon. Adult trees accounted for a maximum share of 94% of woody carbon while lianas and juvenile trees contributed to just 6%. The carbon stock of adult trees and lianas increased with increasing altitude whereas juveniles showed a reverse trend, which could be due to anthropogenic pressures. Human disturbance and cattle grazing should be minimized in the studied tropical dry forest ecosystem to conserve its vanishing natural resources and also to enhance carbon accumulation for the future

Isolation of mosquitocidal bacteria (<i style="mso-bidi-font-style:normal"><span style="mso-bidi-font-weight:bold">Bacillus thuringiensis</span></i><span style="mso-bidi-font-weight:bold">, <i style="mso-bidi-font-style:normal">B.sphaericus</i> and <i style="mso-bidi-font-style: normal">B.cereus</i>) from excreta of arid birds </span>

739-747Mosquitocidal bacteria are environmentally friendly alternatives to chemical insecticides for controlling mosquitoes and therefore, there have been tremendous world-wide efforts to identify novel mosquitocidal bacteria from natural environment. In the present study, excreta from arid-birds were analyzed for identifying mosquitocidal bacteria. The selection of sample for bacterial screening is significant, because, arid-birds are the unique living species and gathering the foods from variety of sources from environment. Out of 1000 samples examined, twelve bacterial strains were identified as mosquitocidal and the 16S rRNA gene sequence alignment depicted that these isolates belonged to Bacillus species (Bacillus thuringiensis, B.sphaericus and B.cereus). Toxicity assay against mosquito vectors have shown that these isolates are potential. The B. sphaericus VCRC-B547 (NCBI: JN377789) has shown a higher toxicity against Cx. quinquefasciatus, An. stephensi, and Aed. aegypti. Result from SDS-PAGE has shown that there was considerable difference in the protein profiles among the new bacterial isolates. Phylogenetic tree with branch length 0.05 revealed three distinct groups with <span style="mso-bidi-font-style: italic">homology among the closely related Bacillus strains. This study therefore throws considerable interest on the diversity of microbial organisms from arid birds and its application in mosquito control. </span