Genome‐wide analysis of polymorphisms identified domestication‐associated long low‐diversity region carrying important rice grain size/weight quantitative trait loci

Rice grain size and weight are major determinants of grain quality and yield and so have been under rigorous selection since domestication. However, the genetic basis for contrasting grain size/weight trait among Indian germplasms and their association with domestication‐driven evolution is not well understood. In this study, two long (LGG) and two short grain (SGG) genotypes were resequenced. LGG (LGR and PB 1121) differentiated from SGG (Sonasal and Bindli) by 504 439 single nucleotide polymorphisms (SNPs) and 78 166 insertion‐and‐deletion polymorphisms. The LRK gene cluster was different and a truncation mutation in the LRK8 kinase domain was associated with LGG. Phylogeny with 3000 diverse rice accessions revealed that the four sequenced genotypes belonged to the japonica group and were at the edge of the clades indicating them to be the potential source of genetic diversity available in Indian rice germplasm. Six SNPs were significantly associated with grain size/weight and the top four of these could be validated in mapping a population, suggesting this study as a valuable resource for high‐throughput genotyping. A contiguous long low‐diversity region (LDR) of approximately 6 Mb carrying a major grain weight quantitative trait loci (harbouring OsTOR gene) was identified on Chromosome 5. This LDR was identified as an evolutionary important site with significant positive selection and multiple selection sweeps, and showed association with many domestication‐related traits, including grain size/weight. The aus population retained more allelic variations in the LDR than the japonica and indica populations, suggesting it to be one of the divergence loci. All the data and analyses can be accessed from the RiceSzWtBase database.     

Antigen-Antibody docking reveals the molecular basis for cross-reactivity of the 1918 and 2009 Influenza A/H1N1 pandemic viruses

To understand the reported cross-reactivity of the 2009 H1N1 and the 1918 H1N1 pandemic viruses we docked the crystal structure of 2D1, an antibody derived from a survivor of the 1918 pandemic, to the structures of hemaglutinin (HA) of the 2009 strain and seasonal H1 vaccine strains. Our studies revealed that 2D1 binds to the 2009 HA at antigenic site 'Sa', with stabilizing contacts, similar to that in an available co-crystal structure of 2D1-1918 HA. However, 2D1 failed to bind to the known antigenic sites in the HAs of seasonal strains. Our study thus reveals the molecular basis for pre-existing immunity in elderly people to the 2009 pandemic virus.     

Advances in Transgenic Rice Biotechnology

Rice is the most amenable crop plant for genetic manipulation amongst monocots due to its small genome size, enriched genetic map, availability of entire genome sequence, and relative ease of transformation. Improvement in agronomic traits of rice is bound to affect a sizeable population since it is a primary source of sustenance. Recent advances like use of ‘clean gene’ technology or matrix attachment regions would help improve rice transformation. Function of several novel genes and their promoters has been analyzed in transgenic rice. Significant progress has been made in introducing traits like herbicide, biotic stress and abiotic stress tolerance. Attempts also have been made to enhance nutritional characteristics of the grain and yield. Identification of genes controlling growth and development can be used to modify plant architecture and heading period. Transgenic rice can serve as a biofactory for the production of molecules of pharmaceutical and industrial utility. The drive to apply transgenic rice for public good as well as commercial gains has fueled research to an all time high. Successful field trials and biosafety of transgenic rice have been reported. This would act as a catalyst for greater acceptance of genetically modified food crops. The lessons learnt from rice can be extended to other cereals thereby opening new opportunities and possibilities.     

Synthesis of benzofuran scaffold-based potential PTP-1B inhibitors

Protein tyrosine phosphatase 1B (PTP-1B) is an enzyme that plays a critical role in down-regulating insulin signaling through dephosphorylation of the insulin receptor. Studies have shown that PTP-1B knockout mice showed increased insulin sensitivity in muscle and liver as well as resistance to obesity. A series of hydroxy benzofuran methyl ketones and their naturally mimicking dimers and linear and angular furanochalcones and flavones have been evaluated as PTP-1B inhibitors. Screened compounds displayed good inhibitory activity.     

CIPK9 targets VDAC3 and modulates oxidative stress responses in Arabidopsis

Calcium (Ca²⁺) is widely recognized as a key second messenger in mediating various plant adaptive responses. Here we show that calcineurin B-like interacting protein kinase CIPK9 along with its interacting partner VDAC3 identified in the present study are involved in mediating plant responses to methyl viologen (MV). CIPK9 physically interacts with and phosphorylates VDAC3. Co-localization, co-immunoprecipitation, and fluorescence resonance energy transfer experiments proved their physical interaction in planta. Both cipk9 and vdac3 mutants exhibited a tolerant phenotype against MV-induced oxidative stress, which coincided with the lower-level accumulation of reactive oxygen species in their roots. In addition, the analysis of cipk9vdac3 double mutant and VDAC3 overexpressing plants revealed that CIPK9 and VDAC3 were involved in the same pathway for inducing MV-dependent oxidative stress. The response to MV was suppressed by the addition of lanthanum chloride, a non-specific Ca²⁺ channel blocker indicating the role of Ca²⁺ in this pathway. Our study suggest that CIPK9-VDAC3 module may act as a key component in mediating oxidative stress responses in Arabidopsis.     

Identification of prosaposin and transgelin as potential biomarkers for gallbladder cancer using quantitative proteomics

Gallbladder cancer is an uncommon but lethal malignancy with particularly high incidence in Chile, India, Japan and China. There is a paucity of unbiased large-scale studies investigating molecular basis of gallbladder cancer. To systematically identify differentially regulated proteins in gallbladder cancer, iTRAQ-based quantitative proteomics of gallbladder cancer was carried out using Fourier transform high resolution mass spectrometry. Of the 2575 proteins identified, proteins upregulated in gallbladder cancer included several lysosomal proteins such as prosaposin, cathepsin Z and cathepsin H. Downregulated proteins included serine protease HTRA1 and transgelin, which have been reported to be downregulated in several other cancers. Novel biomarker candidates including prosaposin and transgelin were validated to be upregulated and downregulated, respectively, in gallbladder cancer using tissue microarrays. Our study provides the first large scale proteomic characterization of gallbladder cancer which will serve as a resource for future discovery of biomarkers for gallbladder cancer.