Primary structure effects on peptide group hydrogen exchange

The rate of exchange of peptide group NH hydrogens with the hydrogens of aqueous solvent is sensitive to neighboring side chains. To evaluate the effects of protein side chains, all 20 naturally occurring amino acids were studied using dipeptide models. Both inductive and steric blocking effects are apparent. The additivity of nearest-neighbor blocking and inductive effects was tested in oligo-and polypeptides and, suprisingly, confirmed. Reference rates for alanine-containing peptides were determined and effects of temperature considered. These results provide the information necessary to evaluate measured protein NH to ND exchange rates by comparing them with rates to be expected for the same amino acid sequence is unstructured aligo- and polypeptides. The application of this approach to protein studies is discussed. © 1993 Wiley-Liss, Inc.     

Geography of underweight and overweight among women in India: A multilevel analysis of 3204 neighborhoods in 26 states

We investigated the geographic distribution and the relationship with neighborhood wealth of underweight and overweight in India. Using multilevel modeling techniques, we calculated state-specific smoothed shrunken state residuals of overweight and underweight, neighborhood and state variation of nutritional status, and the relationships between neighborhood wealth and nutritional status of 76,681 women living in 3204 neighborhoods in 26 Indian states. We found a substantial variation in overweight and underweight at the neighborhood and state levels, net of what could be attributed to individual-level factors. Neighborhood wealth was associated with increased levels of overweight and decreased levels of underweight, and was found to modify the relationship between personal living standard and nutritional status. These findings suggest that interventions to address the double burden of undernutrition and overnutrition in India must take into account state and neighborhood characteristics in order to be successful.     

16α-Hydroxy Steroids: XI. 2β- and 16α-Hydroxylation of 9α-Fluorohydrocortisone by Strains of Streptomyces roseochromogenes

9α-Fluorohydrocortisone is hydroxylated by Streptomyces roseochromogenes in the 16α-, the 2β-, and in both the 16α- and 2β- positions. 16α-Hydroxylation appears to be the more predominant and rapid pathway of transformation. The degree of 2β-hydroxylation is dependent upon the strain used and may be increased to the point of its being a major route or virtually eliminated by the proper selection of isolates.     

Metabolism and function of phenazines in bacteria: impacts on the behavior of bacteria in the environment and biotechnological processes

Phenazines constitute a large group of nitrogen-containing heterocyclic compounds produced by a diverse range of bacteria. Both natural and synthetic phenazine derivatives are studied due their impacts on bacterial interactions and biotechnological processes. Phenazines serve as electron shuttles to alternate terminal acceptors, modify cellular redox states, act as cell signals that regulate patterns of gene expression, contribute to biofilm formation and architecture, and enhance bacterial survival. Phenazines have diverse effects on eukaryotic hosts and host tissues, including the modification of multiple host cellular responses. In plants, phenazines also may influence growth and elicit induced systemic resistance. Here, we discuss emerging evidence that phenazines play multiple roles for the producing organism and contribute to their behavior and ecological fitness.     

Endowing human pancreatic ribonuclease with toxicity for cancer cells

Onconase is an amphibian protein that is now in Phase III clinical trials as a cancer chemotherapeutic. Human pancreatic ribonuclease (RNase 1) is homologous to Onconase but is not cytotoxic. Here, ERDD RNase 1, which is the L86E/N88R/G89D/R91D variant of RNase 1, is shown to have conformational stability and ribonucleolytic activity similar to that of the wild-type enzyme but > 10(3)-fold less affinity for the endogenous cytosolic ribonuclease inhibitor protein. Most significantly, ERDD RNase 1 is toxic to human leukemia cells. The addition of a non-native disulfide bond to ERDD RNase 1 not only increases the conformational stability of the enzyme but also increases its cytotoxicity such that its IC(50) value is only 8-fold greater than that of Onconase. Thus, only a few amino acid substitutions are necessary to make a human protein toxic to human cancer cells. This finding has significant implications for human cancer chemotherapy.     

Oxygen, oxysterols, ouabain, and ozone: a cautionary tale

The recent account of the oxidation of tissue cholesterol by ozone created in human arterial plaques by the oxidation of water by electronically excited (singlet) dioxygen depends on the identification of the oxysterols formed and on the presumption that they are formed uniquely by ozone action. The chief oxysterols found, 3beta-hydroxy-5-oxo-5,6-secocholestan-6-al and 3beta,5-dihydroxy-5beta-B-norcholestane-6beta-carboxaldehyde, were identified as their 2,4-dinitrophenylhydrazones by chromatographic properties and a single mass spectral ion m/z 597 interpreted as [M-H](-). Conventional identification procedures for oxysterols were not conducted. Accordingly, absent other evidence, error may exist; such errors are known in the literature. Moreover, the assertion that ozone be the only oxidant that could form the 5,6-secosterol aldehyde from cholesterol is unproven. Other equally novel unproven processes can be posed. The account of biological ozone mimics prior 30-year-old reports of singlet oxygen itself in biological systems. Lest a similar history develop for biological ozone three topics of steroid oxidation are here reviewed to aid in understanding the current matter. Caution in evaluating the account of biological ozone is warranted.