Revision of the taxonomic position of the Olkhon mountain vole (Rodentia,Cricetidae)

The phylogenetic position of the Olkhon mountain vole (Alticola olchonensis Litvinov, 1960) was studied using the sequences of four nuclear (BRCA, GHR, LCAT, and IRBP) and one mitochondrial (cyt. b) gene. Until now multiple studies of the systematic position of this vole had been based exclusively on morphological data, while the major taxonomic references contain contradictory information regarding both the subgeneric and species status of this animal. It was established that the molecular data and morphology data allow us to concern the Lake Baikal vole unambiguously as a part of the nominative subgenus Alticola instead of Aschizomys.     

Methylation: a regulator of HIV-1 replication?

Pakistan, the second most populous Muslim nation in the world, has started to finally experience and confront the HIV/AIDS epidemic. The country had been relatively safe from any indigenous HIV cases for around two decades, with most of the infections being attributable to deported HIV positive migrants from the Gulf States. However, the virus finally seems to have found a home-base, as evidenced by the recent HIV outbreaks among the injection drug user community. Extremely high-risk behavior has also been documented among Hijras (sex workers) and long-distance truck drivers. The weak government response coupled with the extremely distressing social demographics of this South-Asian republic also helps to compound the problem. The time is ripe now to prepare in advance, to take the appropriate measures to curtail further spread of the disease. If this opportunity is not utilized right now, little if at all could be done later.     

Structure of cytochrome c oxidase: a comparison of the bacterial and mitochondrial enzymes

It has been almost 5 years since the first structures of cytochrome c oxidase, from Paracoccus denitrificans and bovine heart mitochondria, were revealed. Since then many different proton pumping mechanisms have been proposed for the enzyme; however, no definitive conclusion has been achieved. In this article, we revisit the original structures of bacterial and mitochondrial oxidases and try to clarify similarities as well as differences between the two structures.     

Tetracycline up-regulates COX-2 expression and prostaglandin E2 production independent of its effect on nitric oxide

Tetracyclines (doxycycline and minocycline) augmented (one- to twofold) the PGE2 production in human osteoarthritis-affected cartilage (in the presence or absence of cytokines and endotoxin) in ex vivo conditions. Similarly, bovine chondrocytes stimulated with LPS showed (one- to fivefold) an increase in PGE2 accumulation in the presence of doxycycline. This effect was observed at drug concentrations that did not affect nitric oxide (NO) production. In murine macrophages (RAW 264.7) stimulated with LPS, tetracyclines inhibited NO release and increased PGE2 production. Tetracycline(s) and L-N-monomethylarginine (L-NMMA) (NO synthase inhibitor) showed an additive effect on inhibition of NO and PGE2 accumulation, thereby uncoupling the effects of tetracyclines on NO and PGE2 production. The enhancement of PGE2 production in RAW 264.7 cells by tetracyclines was accompanied by the accumulation of both cyclooxygenase (COX)-2 mRNA and cytosolic COX-2 protein. In contrast to tetracyclines, L-NMMA at low concentrations (< or = 100 microM) inhibited the spontaneous release of No in osteoarthritis-affected explants and LPS-stimulated macrophages but had no significant effect on the PGE2 production. At higher concentrations, L-NMMA (500 microM) inhibited NO release but augmented PGE2 production. This study indicates a novel mechanism of action of tetracyclines to augment the expression of COX-2 and PGE2 production, an effect that is independent of endogenous concentration of NO.     

Fractal properties of DNA walks

We describe two dimensional DNA walks, and analyze their fractal properties. We show results for the complete genome of S. cerevisiae. We find that the mean square deviation of the walks is superdifussive, corresponding to a fractal structure of dimension lower than two. Furthermore, the coding part of the genome seems to have smaller fractal dimension, and longer correlations, than noncoding parts.     

Fusion protein approach to improve the crystal quality of cytochrome bo(3) ubiquinol oxidase from Escherichia coli

Crystals of cytochrome bo(3) ubiquinol oxidase from E. coli diffract X-rays to 3.5 A and the structure determination is in progress. The limiting factor to the elucidation of the structural detail is the quality of the crystals; the diffraction spots from the crystals are diffused which leads to difficulties in processing the data beyond 4.0 A. Weak protein-protein contacts within the crystal lattice is assumed to be the cause of this problem. To improve these contacts, we have introduced protein Z to the C-terminal end of the subunit IV of cytochrome bo(3) and expressed both proteins as a single fusion. We have successfully obtained crystals of this fusion protein. The spot shape problem has clearly been solved in the crystals of the fusion protein although further optimization is necessary to obtain higher resolution. We also discuss the potential applications of this approach to the crystallization of membrane proteins in general.     

Skeletal muscle ryanodine receptor is a redox sensor with a well defined redox potential that is sensitive to channel modulators

Hyperreactive sulfhydryl groups associated with the Ca(2+) release protein from sarcoplasmic reticulum are shown to have a well defined reduction potential that is sensitive to the cellular environment. Ca(2+) channel activators lower the redox potential of the ryanodine receptor, which favors the oxidation of thiols and the opening of the Ca(2+) release protein. In contrast, channel inhibitors increase the redox potential, which favors the reduction of disulfides and the closure of the release protein. Modulation of redox potential of reactive thiols may be a general control mechanism by which sarcoplasmic/endoplasmic reticulum, ryanodine receptors/IP(3) receptors, control cytoplasmic Ca(2+) concentrations.