Involvement of non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase in response to oxidative stress

Glyceraldehyde-3-phosphate dehydrogenases catalyze key steps in energy and reducing power partitioning in cells of higher plants. Because non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase (NP-Ga3PDHase) is involved in the production of reductive power (NADPH) in the cytosol, its behavior under oxidative stress conditions was analyzed. The specific activity of the enzyme was found to increase up to 2-fold after oxidative conditions imposed by methylviologen in wheat and maize seedlings. Under moderate oxidant concentration, lack of mRNA induction was observed. The increase in specific activity would thus be a consequence of a significant stability of NP-Ga3PDHase. Our results suggest that the enzyme could be modified by oxidation of cysteine residues, but formation of disulfide bridges is dependent on levels of divalent cations and 14-3-3 proteins. The latter differential effect could be critical to relatively maintain energy and reductant levels in the cytoplasm of plant cells under oxidative stress.     

The Population Reference Sample, POPRES: a resource for population, disease, and pharmacological genetics research

Technological and scientific advances, stemming in large part from the Human Genome and HapMap projects, have made large-scale, genome-wide investigations feasible and cost effective. These advances have the potential to dramatically impact drug discovery and development by identifying genetic factors that contribute to variation in disease risk as well as drug pharmacokinetics, treatment efficacy, and adverse drug reactions. In spite of the technological advancements, successful application in biomedical research would be limited without access to suitable sample collections. To facilitate exploratory genetics research, we have assembled a DNA resource from a large number of subjects participating in multiple studies throughout the world. This growing resource was initially genotyped with a commercially available genome-wide 500,000 single-nucleotide polymorphism panel. This project includes nearly 6,000 subjects of African-American, East Asian, South Asian, Mexican, and European origin. Seven informative axes of variation identified via principal-component analysis (PCA) of these data confirm the overall integrity of the data and highlight important features of the genetic structure of diverse populations. The potential value of such extensively genotyped collections is illustrated by selection of genetically matched population controls in a genome-wide analysis of abacavir-associated hypersensitivity reaction. We find that matching based on country of origin, identity-by-state distance, and multidimensional PCA do similarly well to control the type I error rate. The genotype and demographic data from this reference sample are freely available through the NCBI database of Genotypes and Phenotypes (dbGaP).     

Directional selection and the site-frequency spectrum.

In this article we explore statistical properties of the maximum-likelihood estimates (MLEs) of the selection and mutation parameters in a Poisson random field population genetics model of directional selection at DNA sites. We derive the asymptotic variances and covariance of the MLEs and explore the power of the likelihood ratio tests (LRT) of neutrality for varying levels of mutation and selection as well as the robustness of the LRT to deviations from the assumption of free recombination among sites. We also discuss the coverage of confidence intervals on the basis of two standard-likelihood methods. We find that the LRT has high power to detect deviations from neutrality and that the maximum-likelihood estimation performs very well when the ancestral states of all mutations in the sample are known. When the ancestral states are not known, the test has high power to detect deviations from neutrality for negative selection but not for positive selection. We also find that the LRT is not robust to deviations from the assumption of independence among sites.     

Relating Single-Molecule Measurements to Thermodynamics

Measurements made on large ensembles of molecules are routinely interpreted using thermodynamics, but the normal rules of thermodynamics may not apply to measurements made on single molecules. Using a polymer stretching experiment as an example, it is shown that in the limit of a single, short molecule the outcome of experimental measurements may depend on which variables are held fixed and which are allowed to fluctuate. Thus an experiment in which the end-to-end distance of the polymer molecule is fixed and the tension fluctuates yields a different result than an experiment where the force is fixed and the end-to-end distance fluctuates. It is further shown that this difference is due to asymmetry in the distribution of end-to-end distances for a single molecule, and that the difference vanishes in the appropriate thermodynamic limit; that is, as the polymer molecule becomes long compared to its persistence length. Despite these differences, much of the thermodynamic formalism still applies on the single-molecule level if the thermodynamic free energies are replaced with appropriate potentials of mean force. The primary remaining differences are consequences of the fact that unlike the free energies, the potentials of mean force are not in general homogeneous functions of their variables. The basic thermodynamic concepts of an intensive or extensive quantity, and the thermodynamic relationships that follow from them, are therefore less useful for interpreting single-molecule experiments.     

Serum, zinc, copper and insulin in diabetes mellitus

We studied serum zinc, copper, ceruloplasmin, insulin, basal glycemia and cholesterol in 49 diabetics on oral anti-diabetic agent and in 10 normal people. We found there is an elevation of serum zinc, copper and ceruloplasmin in the diabetic group that is statistically significant (p less than 0.001). There is a significant correlation between zinc and insulin (p less than 0.001), and between the quotient zinc/copper and cholesterol (p less than 0.001). The increase of plasma zinc can reflect a deficient storage or a chronic hypersecretion of insulin in hyperglucemic patients. We think that the quotient zinc/copper/might play a role in the pathogenesis of the arteriosclerosis in diabetes.     

Disseminated cutaneous and vascular invasion byFusarium moniliforme in a fatal case of acute lymphocytic leukemia

A 35 year old female patient with acute lymphocytic leukemia developed fusariosis in which dissemination appeared to be limited to cutaneous and vascular invasion. The first evidence of fungemia occurred nearly seven months after initial hospitalization. The fungus was identified asFusarium sp. and was considered a contaminant. Two weeks later blood cultures were again positive forFusarium sp. and the patient was placed on amphotericin B and 5-fluorocytosine therapy. The following day developing lesions were noted on her forearms and face; lesions ultimately spread to her trunk, abdomen, and lower extremities. Skin lesion biopsy sections revealed abundant septate and branching hyphae throughout the dermis and within capillaries. Twenty-six days after the initial isolation the patient died. Post-mortem blood cultures gave rise to the same fungus, which was identified asFusarium monoliforme. Postmortem cultures and stains of spleen, liver, lung, and brain specimens were all negative for fungi. The primary source and portal of entry of the organism remained undetermined.