Reduction of clofazimine by mycobacterial type 2 NADH:quinone oxidoreductase: a pathway for the generation of bactericidal levels of reactive oxygen species.

The mechanism of action of clofazimine (CFZ), an antimycobacterial drug with a long history, is not well understood. The present study describes a redox cycling pathway that involves the enzymatic reduction of CFZ by NDH-2, the primary respiratory chain NADH:quinone oxidoreductase of mycobacteria and nonenzymatic oxidation of reduced CFZ by O(2) yielding CFZ and reactive oxygen species (ROS). This pathway was demonstrated using isolated membranes and purified recombinant NDH-2.

Bach1 modulates heme oxygenase-1 expression in the neonatal mouse lung.

Heme oxygenase-1 (HO-1), the rate-limiting enzyme of heme degradation and antioxidant defense protein, is induced in the lungs of animals exposed to hyperoxia. However, high levels of HO-1 expression may be deleterious, thus necessitating tight regulation. Previous reports show maturational differences in rat HO-1 regulation in hyperoxia, as newborns do not up-regulate HO-1mRNA compared with adults.

Human imprinted chromosomal regions are historical hot-spots of recombination.

Human recombination rates vary along the chromosomes as well as between the two sexes. There is growing evidence that epigenetic factors may have an important influence on recombination rates, as well as on crossover position. Using both public database analysis and wet-bench approaches, we revisited the relationship between increased rates of meiotic recombination and genome imprinting.

Interindividual variability and parent of origin DNA methylation differences at specific human Alu elements.

We investigated the CpG methylation of 19 specific members of Alu sub-families in human DNA isolated from whole blood, using an assay based on methylation-sensitive restriction endonuclease digestion of genomic DNA and 'hot-stop' polymerase chain reaction. We found significant interindividual variability in the level of methylation for specific Alu elements among the members of 48 three-generation families. Surprisingly, some of the elements also displayed quantitative parent of origin methylation differences; i.