Barbiturates inhibit intracellular Ca2+ rise induced by thrombin in rat platelets

The effects of a number of barbiturates (anesthetic as well as anticonvulsant) on thrombin-induced calcium mobilization were tested in rat platelets using the fluorescent Ca2+ probe Fura-2. All drugs, except barbituric acid and Na-barbital, inhibited the thrombin-induced intracellular Ca2+ rise. Both the uptake of extracellular Ca2+ and the release of calcium from intracellular organelles were affected but influx was inhibited more strongly and at lower concentrations of the drugs (e.g. IC50 of thiopental was 0.83 mM for influx and 1.2 mM for intracellular release). Inhibitory potencies of the various barbiturates were markedly different. Thiopental was the most and barbital the least potent inhibitor. The order of inhibitory potency of the drugs appeared generally to follow their lipid solubility and the order of their hypnotic efficiency, with hexobarbital as the most conspicuous exception. Therefore, barbiturate treatment of cells perturbs agonist-induced calcium mobilization. This effect may be partially linked to their previously reported inhibitory action on two kinases, protein kinase C and phosphatidylinositol 4-phosphate kinase [1, 2].     

Lipase in aqueous‐polar organic solvents: Activity,structure, and stability

Studying alterations in biophysical and biochemical behavior of enzymes in the presence of organic solvents and the underlying cause(s) has important implications in biotechnology. We investigated the effects of aqueous solutions of polar organic solvents on ester hydrolytic activity, structure and stability of a lipase. Relative activity of the lipase monotonically decreased with increasing concentration of acetone, acetonitrile, and DMF but increased at lower concentrations (upto ～20% v/v) of dimethylsulfoxide, isopropanol, and methanol. None of the organic solvents caused any appreciable structural change as evident from circular dichorism and NMR studies, thus do not support any significant role of enzyme denaturation in activity change. Change in 2D [15N, 1H]‐HSQC chemical shifts suggested that all the organic solvents preferentially localize to a hydrophobic patch in the active‐site vicinity and no chemical shift perturbation was observed for residues present in protein's core. This suggests that activity alteration might be directly linked to change in active site environment only. All organic solvents decreased the apparent binding of substrate to the enzyme (increased K_m); however significantly enhanced the k_cat. Melting temperature (T_m) of lipase, measured by circular dichroism and differential scanning calorimetry, altered in all solvents, albeit to a variable extent. Interestingly, although the effect of all organic solvents on various properties on lipase is qualitatively similar, our study suggest that magnitudes of effects do not appear to follow bulk solvent properties like polarity and the solvent effects are apparently dictated by specific and local interactions of solvent molecule(s) with the protein.     

Mining the Cicer arietinum genome for the mildew locus O (Mlo) gene family and comparative evolutionary analysis of the Mlo genes from Medicago truncatula and some other plant species

Journal of Plant Research - The mildew locus O (Mlo) gene family is ubiquitous in land plants. Some members of this gene family are involved in negative regulation of powdery mildew resistance,...     

Estimation in a Continuous State Space Branching Process

In some biological studies it is impossible to count the total number of individuals, but the size of the population can be measured by it's weight or volume. The probability of extinction of such populations is an interesting parameter, e.g. in modelling of epidemics. In this paper, the estimation of extinction probability and the moments of the offspring distribution is studied and the asymptotic properties of the estimators are discussed.     

Effects of arginine-free diet on urea cycle enzymes in young and adult ferrets

Young ferrets develop hyperammonemia soon after eating an arginine-free diet, whereas adult ferrets do not develop hyperammonemia after an identical treatment. Earlier reports indicate that young or adult rats do not develop hyperammonemia and encephalopathy after a single meal of an arginine-free diet. The effects of a single feeding of an arginine-free diet on the urea cycle enzyme activities in the liver of young and adult ferrets is reported. Ornithine carbamyl transferase, carbamyl phosphate synthetase and ornithine aminotransferase activities in the livers of adult ferrets were significantly higher than those in the livers of young ferrets. A single meal of an arginine-free diet did not alter the urea cycle enzyme activities in the liver of young or adult ferrets. The levels of urea cycle enzymes in the liver and kidney of young ferrets were comparable to those in rat liver and kidney. The results suggest that the hyperammonemia observed in young ferrets following a single meal of an arginine-free diet may not be due to the deficiency of enzyme activities.     

Molecular simulation study of the effect of cross-linker on the properties of poly(N-isopropyl acrylamide) hydrogel

Molecular simulation techniques have been utilised to investigate the effect of cross-linker type on the structural and dynamical properties of a temperature-sensitive hydrogel, poly (N-isopropyl acrylamide) (PNIPAM) across its lower critical solution temperature (LCST). PNIPAM exhibits an LCST at ～305 K, above which it collapses and below which it is swollen. Molecular dynamics simulations of PNIPAM hydrogel cross-linked with N, N′-methylene bisacrylamide (BIS) and ethylene glycol dimethacrylate (EGD) cross-linkers were carried out below, at and above its LCST (namely 300, 305 and 310 K, respectively). Structural analysis indicates that the cross-linkers did not affect the temperature of the onset of the LCST, but did affect the degree of swelling and pore size distribution, where the EGD-cross-linked hydrogel exhibited a greater degree of structural change than that of the BIS-cross-linked hydrogel. We believe that this could be attributed to the longer chain length and more flexible nature of the EGD cross-linker compared to the BIS cross-linkers.