Conformation of a cyclic decapeptide analog of a repeat pentapeptide sequence of elastin: cyclo-bis(valyl-prolyl-alanyl-valyl-glycyl)

The conformation of a cyclic decapeptide analog of a repeat sequence of elastin has been determined in the crystalline state using X-ray crystallographic techniques. Tetragonal crystals were grown from a solution of the decapeptide in water; space group P4(2)2(1)2, a = 19.439(2) & c = 13.602(1) A, with four formula units (C40H66N10O10.4H2O) per unit cell. The cyclic decapeptide in the crystal exhibits exact twofold symmetry. The asymmetric unit contains one pentapeptide and two water molecules for a total of 32 nonhydrogen atoms. The structure has been determined by the application of direct methods and refined by full-matrix least squares to an R index of 0.053 for 2272 reflections with intensities greater than 2 sigma(I). The backbone conformation of the asymmetric pentapeptide can be described as consisting of a double beta bend of Type III-I. The Type III turn has Pro (phi = -59.3 degrees, psi = -26.8 degrees) and Ala (phi = -65.9 degrees, psi = -23.1 degrees) at the corners while Type I turn has Ala (phi = -65.9 degrees, psi = -23.1 degrees) and Val (phi = -98.9 degrees, psi = 8.3 degrees) as the corner residues. The cyclic decapeptide has two such double bends linked together by Gly-Val bridges.     

Synthesis and structure–activity studies of novel homomorpholine oxazolidinone antibacterial agents

A novel series of oxazolidinones were synthesized in which the morpholine C-ring of linezolid was replaced with homomorpholine. In addition to investigating the effect of a homomorpholine C-ring on antibacterial activity, the effect of des-, mono-, di-, and tri-fluoro substitution on the phenyl B-ring was investigated as well. Various C-5 functional groups were also examined, including acetamides and triazoles and carboxamides.     

Synthesis of DNA interactive C3-trans-cinnamide linked β-carboline conjugates as potential cytotoxic and DNA topoisomerase I inhibitors

A series of new C3-trans-cinnamide linked β-carboline conjugates has been synthesized by coupling between various β-carboline amines and substituted cinnamic acids. Evaluation of their anti-proliferative activity against a panel of selected human cancer cell lines such as A549 (lung cancer), MCF-7 (breast cancer), B16 (melanoma), HeLa (cervical cancer) and a normal cell line NIH3T3 (mouse embryonic fibroblast cell line), suggested that the newly designed conjugates are considerably active against all the tested cancer cell lines with IC₅₀ values 13–45?nM. Moreover, the conjugates 8v and 8x were the most active against MCF-7 cells (14.05?nM and 13.84?nM respectively) and also even potent on other cell lines tested. Further, detailed investigations such as cell cycle analysis, apoptosis induction study, topoisomerase I inhibition assay, DNA binding affinity and docking studies revealed that these new conjugates are DNA interactive topoisomerase I inhibitors.     

Quantifying nationwide land cover and historical changes in forests of Nepal (1930–2014): implications on forest fragmentation

This study quantifies the nationwide land cover and long-term changes in forests and its implications on forest fragmentation in Nepal. The multi-source datasets were used to generate the forest cover information for 1930, 1975, 1985, 1995, 2005 and 2014. This study analyzes distribution of land cover, rate of deforestation, changes across forest types, forest canopy density and pattern of fragmentation. The land cover legend for 2014 is consisting of 21 classes: tropical dry deciduous sal forest, tropical moist deciduous sal forest, subtropical broad-leaved forest, subtropical pine forest, lower temperate broad leaved forest, upper temperate broad leaved forest, lower temperate mixed broad leaved forest, upper temperate mixed broad leaved forest, temperate needle leaved forest, subalpine forest, plantations, tropical scrub, subtropical scrub, temperate scrub, alpine scrub, grassland, agriculture, water bodies, barren land and settlements. The forest cover statistics for Nepal obtained in this study shows an area of 76,710 km² in 1930 which has decreased to 39,392 km² in 2014. A net loss of 37,318 km² (48.6%) was observed in last eight decades. Analysis of annual rate of net deforestation for the recent period indicates 0.01% during 2005–2014. An increase in the number of forest patches from 6925 (in 1930) to 42,961 (in 2014) was noticed. The significant observation is 75.5% of reduction in core 3 forest, whereas, patch, perforated and edge classes show the increase in percentage of fragmentation classes from 1930 to 2014. The results of this work will support the understanding of deforestation and its consequences on fragmentation for maintaining and improving the forest resources of Nepal.     

Identification,characterization, expression profiling,and virus-induced gene silencing of armadillo repeat-containing proteins in tomato suggest their involvement in <Emphasis Type="Italic">tomato leaf curl New Delhi virus</Emphasis> resistance

Armadillo repeat family is well-characterized in several plant species for their involvement in multiple regulatory processes including growth, development, and stress response. We have previously shown a three-fold higher expression of ARM protein-encoding in tomato cultivar tolerant to tomato leaf curl New Delhi virus (ToLCNDV) compared to susceptible cultivar upon virus infection. This suggests the putative involvement of ARM proteins in defense response against virus infection; however, no comprehensive investigation has been performed to address this inference. In the present study, we have identified a total of 46 ARM-repeat proteins (SlARMs), and 41 U-box-containing proteins (SlPUBs) in tomato. These proteins and their corresponding genes were studied for their physicochemical properties, gene structure, domain architecture, chromosomal localization, phylogeny, and cis-regulatory elements in the upstream promoter region. Expression profiling of candidate genes in response to ToLCNDV infection in contrasting tomato cultivars showed significant upregulation of SlARM18 in the tolerant cultivar. Virus-induced gene silencing of SlARM18 in the tolerant tomato cultivar conferred susceptibility, which suggests the involvement of this gene in resistance mechanism. Further studies are underway to functionally characterize SlARM18 to delineate its precise role in defense mechanism.