NOPR Collection:

Gene pyramiding: A strategy for insect resistance management in Bt transgenic crops

2016-12-29T10:16:28Z

Title: Gene pyramiding: A strategy for insect resistance management in Bt transgenic crops Authors: Sushmita, K; Ramesh, B; Pattanayak, Debasis; Kumar, P Ananda Abstract: Preventing or delaying evolution of resistance in insects through adoption of judicial resistance management strategy is critical for the sustainable use of Bt transgenic crops. Strategies for resistance management in insect resistant Bt crops include: high dose strategy, moderate dose strategy, temporal- or time-specific toxins expression, refuge strategy, gene pyramiding/stacking, mixtures, rotations or mosaics of transgenic plants. Among these, pyramided/stacked plants have the potential to delay resistance more effectively than sequential deployment of single Bt toxin containing plants or in mosaics, even with relatively small and more economically acceptable refuge size. Resistance can be delayed for extended period even by reducing the refuge size if two or more toxin coding genes are pyramided in a single plant. If toxins are used independently, there is a possible risk of cross-resistance among the toxins. Page(s): 283-291

In silico designing of drugs for the inhibition of AMF-HER2 complex in trastuzumab resistant breast cancer

2016-12-29T10:10:01Z

Title: In silico designing of drugs for the inhibition of AMF-HER2 complex in trastuzumab resistant breast cancer Authors: Devgan, Manish; Karar, Pardip Kumar; Agarwal, Gourav; Mohan, Ankur; Gangwar, Pallavi Abstract: About 20 to 25% of human metastatic breast cancer over-expresses the human epidermal growth factor receptor 2 (HER2). With the introduction of HER2-targeted therapies, in particular trastuzumab, HER2 status has become more important. The autocrine motility factor (AMF) is a protein factor expressed and secreted by cancer cells. The interaction of AMF with HER2 triggers HER2 phosphorylation, which leads to the development of resistance against trastuzumab. In this work, a theoretical model of AMF was generated using the concepts of homology modeling and loop modeling. The resulting model was validated by Procheck with Ramachandran plot analysis. The ligands generated with the help of Drug bank were docked against AMF using AutoDock Vina in PyRx 0.8. The structure of compound (DB04493) with least binding energy (-15.5 kcal/mol) was varied by using ACD/ChemSketch 8.0 and the docking was done for the resulting 20 new ligands. The study revealed that the compound fructose-6-phosphate (DB04493) has the maximum probability to bind with AMF. The combination of AMF inhibitor with trastuzumab can potentiate the growth inhibitory and anti-invasive actions of trastuzumab in breast cancer cells. Page(s): 292-298

Identification of functional SNPs in VEGF gene and in silico analysis of damaging SNPs based on data procured from dbSNP database

2016-12-29T10:02:08Z

Title: Identification of functional SNPs in VEGF gene and in silico analysis of damaging SNPs based on data procured from dbSNP database Authors: Dabhi, Brijesh; Mistry, Kinnari N Abstract: VEGF (vascular endothelial growth factor) gene is known to cause angiogenesis and participate in many diseases like prostate cancer and diabetic retinopathy. Several single nucleotide polymorphisms (SNPs) have been described in the VEGF gene, some of which have been reported to be associated with differential expression of VEGF in vitro. In the present study, polymorphism of VEGF gene was studied in relation to damaging mutations. Of total SNPs in VEGF gene, 38 were non-synonymous SNPs (nsSNPs), 47 were synonymous SNPs, 66 were in non-coding regions, which comprised of 13 SNPs in 5'UTR region and 53 SNPs were in 3'UTR region. The rest were in the intronic region. SIFT (Sorting Intolerant from Tolerant) analysis showed that L163P, H200W, P312T, R288W and G365V mutations were damaging, whereas PolyPhen predicted P163L and H200W nsSNPs as damaging. Among the predicted nsSNPs, rs4645843, rs1800620 were identified as deleterious and damaging by the SIFT and PolyPhen programs. Protein structural analysis with these amino acid variants was performed by using I-Mutant, Swiss PDB viewer, ANOLEA (Atomic Non-Local Environment Assessment), MUSTER (MUlti-Sources ThreadER) and NOMAD-Ref servers to check their molecular dynamics and energy minimization calculations. This in silico analysis suggested that mutations in VEGF, such as, G365V, P312T and R288W, could directly or indirectly destabilize the amino acid interactions and hydrogen bond networks, thus explaining the functional deviations of protein to some extent. Thus screening for VEGF G365V, P312T and R288W variants in the population-based study may be useful to check disease susceptibility. Page(s): 299-305

Immuno-reactivity pattern of secretory proteins of Mycobacterium avium subspecies paratuberculosis vaccine strain ‘S 5’ with potential for diagnosis of Johne's disease in early infection

2016-12-29T09:56:51Z

Title: Immuno-reactivity pattern of secretory proteins of Mycobacterium avium subspecies paratuberculosis vaccine strain ‘S 5’ with potential for diagnosis of Johne's disease in early infection Authors: Gupta, Saurabh; Singh, Shoor Vir; Bhatia, A K Abstract: Diagnosis of Johne's disease (JD) is hampered by the lack of specific immune-reactive antigens. Therefore, studies should be focused on the search of new candidate antigenic epitopes as 'novel biomarkers' for early diagnosis of JD. Secretory proteins profile of novel biotype (‘S 5’) of 'Indian Bison Type' and their immuno-reactivity was studied in early growth period (4 & 6 wk). Analysis of harvested CF (culture filterate) proteins was done by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Immunoblotting showed strong reactivity of 4 CF proteins (19, 36-38 and 65 kDa). Additional 48 kDa protein was recognized at 6 wk using MAP infected caprine serum. Diagnostic potential of early phase secretory proteins was evaluated using Indirect ELISA test. Results showed slightly lower sensitivity and 100.0% specificity with respect to whole cell sonicated semi-purified protoplasmic antigen (sPPA). Our earlier studies clearly exhibited that there cannot be universally effective diagnostic kits in case of chronic insidious diseases like Johne's disease. Therefore efforts should be to use antigen candidates from locally prevalent strains. By using commercially available universal kits we are unknowingly grossly under reporting the disease prevalence/incidence. Page(s): 306-312