Lack of Wdr13 Gene in Mice Leads to Enhanced Pancreatic Beta Cell Proliferation, Hyperinsulinemia and Mild Obesity

WD-repeat proteins are very diverse, yet these are structurally related proteins that participate in a wide range of cellular functions. WDR13, a member of this family, is conserved from fishes to humans and localizes into the nucleus. To understand the in vivo function(s) of Wdr13 gene, we have created and characterized a mutant mouse strain lacking this gene. The mutant mice had higher serum insulin levels and increased pancreatic islet mass as a result of enhanced beta cell proliferation. While a known cell cycle inhibitor, p21, was downregulated in the mutant islets, over expression of WDR13 in the pancreatic beta cell line (MIN6) resulted in upregulation of p21, accompanied by retardation of cell proliferation. We suggest that WDR13 is a novel negative regulator of the pancreatic beta cell proliferation. Given the higher insulin levels and better glucose clearance in Wdr13 gene deficient mice, we propose that this protein may be a potential candidate drug target for ameliorating impaired glucose metabolism in diabetes

Napin from Brassica juncea: Thermodynamic and structural analysis of stability

The napin from Brassica juncea, oriental mustard, is highly thermostable, proteolysis resistant and allergenic in nature. It consists of two subunits – one small (29 amino acid residues) and one large (86 amino acids residues) – held together by disulfide bonds. The thermal unfolding of napin has been followed by differential scanning calorimetry (DSC) and circular dichroism (CD) measurements. The thermal unfolding is characterized by a three state transition with $T_{M1}$ and $T_{M2}$ at 323.5 K and 335.8 K, respectively; $\Delta C_{P1}$ and $\Delta C_{P2}$ are $2.05 kcal mol^{-1} K^{-1}$ and $1.40 kcal mol^{−1} K^{−1}$, respectively. In the temperature range 310–318 K, the molecule undergoes dimerisation. Isothermal equilibrium unfolding by guanidinium hydrochloride also follows a three state transition, N⇆I⇆U with $\Delta G_{1H2O}$ and $\Delta G_{2H2O}$ values of $5.2 kcal mol^{−1}$ and $5.1 kcal mol^{−1}$ at 300 K, respectively. Excess heat capacity values obtained, are similar to those obtained from DSC measurements. There is an increase in hydrodynamic radius from $20 \AA$ to $35.0 \AA$ due to unfolding by guanidinium hydrochloride. In silico alignment of sequences of napin has revealed that the internal repeats (40%) spanning residues 31 to 60 and 73 to 109 are conserved in all Brassica species. The internal repeats may contribute to the greater stability of napin. A thorough understanding of the structure and stability of these proteins is essential before they can be exploited for genetic improvements for nutrition

Precipitation climatology over India: validation with observations and reanalysis datasets and spatial trends

Changing rainfall patterns have significant effect on water resources, agriculture output in many countries, especially the country like India where the economy depends on rain-fed agriculture. Rainfall over India has large spatial as well as temporal variability. To understand the variability in rainfall, spatial–temporal analyses of rainfall have been studied by using 107 (1901–2007) years of daily gridded India Meteorological Department (IMD) rainfall datasets. Further, the validation of IMD precipitation data is carried out with different observational and different reanalysis datasets during the period from 1989 to 2007. The Global Precipitation Climatology Project data shows similar features as that of IMD with high degree of comparison, whereas Asian Precipitation-Highly-Resolved Observational Data Integration Towards Evaluation data show similar features but with large differences, especially over northwest, west coast and western Himalayas. Spatially, large deviation is observed in the interior peninsula during the monsoon season with National Aeronautics Space Administration-Modern Era Retrospective-analysis for Research and Applications (NASA-MERRA), pre-monsoon with Japanese 25 years Re Analysis (JRA-25), and post-monsoon with climate forecast system reanalysis (CFSR) reanalysis datasets. Among the reanalysis datasets, European Centre for Medium-Range Weather Forecasts Interim Re-Analysis (ERA-Interim) shows good comparison followed by CFSR, NASA-MERRA, and JRA-25. Further, for the first time, with high resolution and long-term IMD data, the spatial distribution of trends is estimated using robust regression analysis technique on the annual and seasonal rainfall data with respect to different regions of India. Significant positive and negative trends are noticed in the whole time series of data during the monsoon season. The northeast and west coast of the Indian region shows significant positive trends and negative trends over western Himalayas and north central Indian region