Mungbean Yellow Mosaic India Virus (MYMIV) belonging to the genus begomovirus causes the yellow mosaic disease in a number of economically important edible grain legumes including mungbean (Vigna radiata), urdbean (Vigna mungo) and soybean (Glycine max). The disease is severe, critical, open spread and inflicts heavy yield losses annually. The objective of this study is to develop molecular markers linked to MYMIV-resistance to facilitate genotyping of urdbean and mungbean germplasms for MYMIV-reaction. Resistance-linked molecular markers were successfully developed from consensus motifs of other resistance (R) gene or R gene homologue sequences. Applying linked marker-assisted genotyping, plant breeders can carry out repeated genotyping throughout the growing season in absence of any disease incidence. Two MYMIV-resistance marker loci, YR4 and CYR1, were identified and of these two CYR1 is completely linked with MYMIV-resistant germplasms and co-segregating with MYMIV-resistant F₂, F₃ progenies of urdbean. The present study demonstrated that these two markers could be efficiently employed together in a multiplex-PCR-reaction for genotyping both V. mungo and V. radiata germplasms from field grown plants and also directly from the seed stock. This method of genotyping would save time and labour during the introgression of MYMIV-resistance through molecular breeding, as methods of phenotyping against begomoviruses are tedious, labour and time intensive.

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TN16 is one of the most promising inhibitors of α, β dimer of tubulin that occupies the cavity in the β-subunit located at the dimeric interface, known as the colchicine binding site. The experimentally determined structure of the complex (Protein Data Bank entry 3HKD) presents the conformation and position of the ligand based on the "best fit", keeping the controversy of other significant binding modes open for further investigation. Computation has already revealed that TN16 experiences fluctuations within the binding pocket, but the insight from that previous report was limited by the shorter windows of sampling and by the approximations on the surrounding environment by implicit solvation. This article reports that in most of the cases straightforward MMGBSA calculations of binding energy revealed a gradual loss of stabilization that was inconsistent with the structural observations, and thus, it indicated the lack of consideration of stabilizing factors with appropriate weightage. Consideration of the structurally packed water molecules in the space between the ligand and receptor successfully eliminated such discrepancies between the structure and stability, serving as the "litmus test" of the importance of explicit consideration of such structurally packed water in the calculations. Such consideration has further evidenced a quasi-degenerate character of the different binding modes of TN16 that has rationalized the observed intrinsic fluctuations of TN16 within the pocket, which is likely to be the most critical insight into its entropy-dominated binding. Quantum mechanical calculations have revealed a relay of electron density from TN16 to the protein via a water molecule in a concerted manner.

We successfully produced two human ␤-defensins (hBD-1 and hBD-2) in bacteria as functional peptides and tested their antibacterial activities against Salmonella enterica serovar Typhi, Escherichia coli, and Staphylococcus aureus employing both spectroscopic and viable CFU count methods. Purified peptides showed approximately 50% inhibition of the bacterial population when used individually and up to 90% when used in combination. The 50% lethal doses (LD 50 ) of hBD-1 against S. Typhi, E. coli, and S. aureus were 0.36, 0.40, and 0.69 g/l, respectively, while those for hBD-2 against the same bacteria were 0.38, 0.36, and 0.66 g/l, respectively. Moreover, we observed that bacterium-derived antimicrobial peptides were also effective in increasing survival time and decreasing bacterial loads in the peritoneal fluid, liver, and spleen of a mouse intraperitoneally infected with S. Typhi. The 1:1 hBD-1/hBD-2 combination showed maximum effectiveness in challenging the Salmonella infection in vitro and in vivo. We also observed less tissue damage and sepsis formation in the livers of infected mice after treatment with hBD-1 and hBD-2 peptides individually or in combination. Based on these findings, we conclude that bacterium-derived recombinant ␤-defensins (hBD-1 and hBD-2) are promising antimicrobial peptide (AMP)-based substances for the development of new therapeutics against typhoid fever.

Yellow mosaic disease of Vigna mungo caused by Mungbean yellow mosaic India virus (MYMIV) is still a major threat in the crop production. A candidate disease resistance (R) gene, CYR1 that co-segregates with MYMIV-resistant populations of V. mungo has been isolated. CYR1 coded in silico translated protein sequence comprised of 1,176 amino acids with coiled coil structure at the N-terminus, central nucleotide binding site (NBS) and C-terminal leucine-rich repeats (LRR) that belongs to non-TIR-NBS-LRR subfamily of plant R genes. CYR1 transcript was unambiguously expressed during incompatible plant virus interactions. A putative promoter-like sequence present upstream of this candidate gene perhaps regulates its expression. Enhanced transcript level upon MYMIV infection suggests involvement of this candidate gene in conferring resistance against the virus. In silico constructed 3D models of NBS and LRR regions of this candidate protein and MYMIV-coat protein (CP) revealed that CYR1-LRR forms an active pocket and successively interacts with MYMIV-CP during docking, like that of receptor-ligand interaction; indicating a critical role of CYR1 as signalling molecule to protect V. mungo plants from MYMIV. This suggests involvement of CYR1 in recognizing MYMIV-effector molecule thus contributing to incompatible interaction. This study is the first stride to understand molecular mechanism of MYMIV resistance.

Introduction:The prospective interventional single-institution randomized control study was carried out to compare the pain relieving efficacy among different bisphosphonates at the cost of incidence of skeletal-related events (SRE).Materials and Methods:During June 2008 and May 2011, 256 patients with painful bone metastasis in solid tumors with a pain score of at least 5 were randomized into three arms: zoledronic acid (4 mg, i.v.), ibandronate (6 mg, i.v.) and pamidronate (90 mg, i.v.). Radiation was given to all patients, either 800 cGy single fraction or 20 Gy in five fractions. The ANOVA test was used for analysis. The Pearson test was used to correlate pain scores with proportions of responders as statistical estimation of pain relief.Results:With a mean baseline pain score of 6.5 ± 1.2, there was no difference in pain scores among the three treatment arms, assessed at 3 months and at the end of the study. However, the pain scores at 6 months were statistically reduced in zoledronic acid-receiving patients (1.5 ± 0.4) unlike the scores in patients receiving ibandronate (3.1 ± 0.5) and pamidronate (2.3 ± 0.4), with a P-value of 0.024. The response was statistically significant at 6 months (0.039) and at the end of the study (0.023), in favor of zoledronic acid. Pearson's correlation demonstrated a statistically significant positive correlation between pain scores and response rates. There were no statistical differences in the narcotic scores among the treatment arms during the study period. The overall duration of pain relief was not different in any of treatment arms. The time of detection of hypercalcemia was no different; however, the incidence of hypercalcemia was significantly less in the zoledronic acid arm (28.3%) against 44.6% and 50% in ibandronate and pamidronate arms, respectively, with a P-value of 0.041.Conclusion:The use of bisphosphonates for 6 months or more results in a statistical significant improvement in bone pain, more so with zoledronic acid. Hypercalcemia, an SRE, was significantly less in the zoledronic acid arm.

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