30% oxygen inhalation enhances cognitive performance through robust activation in the brain

This study aimed to investigate whether inhalation of the air with 30% oxygen compared with normal air enhances cognitive functioning through increased activation in the brain. The verbal and visuospatial tasks were performed while brain images were scanned. The results showed that there were improvements in performance and also increased activation in several brain areas under the condition of 30% oxygen. These results suggest that a higher concentration of the inhaled oxygen increases the saturation of the blood oxygen in the brain, and facilitates cognitive performance.     

Characterization of new microglia-like cells obtained from neonatal rat brain

We isolated spontaneously proliferating cells from primary astrocyte-enriched cultures prepared from neonatal rat brain. These cells proliferated and retained their characteristics for up to 50 generations. They expressed the microglial marker, OX42, but not glial fibrillary acidic protein, an astroglial marker. In addition, they possessed phagocytotic activity, and, when stimulated by lipopolysaccharide (LPS) or interferon-gamma (IFN-gamma), they expressed proinflammatory mediators, including cytokines (i.e., interleukin (IL)-1beta and tumor necrosis factor-alpha) and chemokines (i.e., IL-8 and monocyte chemotactic protein-1). Protein expression of inducible nitric oxide synthase and cyclooxygenase-2, and production of NO by these cells were induced by LPS or IFN-gamma. Thus, these cells possess the characteristics of microglia and can be used as a rat microglial cell line.     

Histone H3 lysine 56 acetylation and the response to DNA replication fork damage

In Saccharomyces cerevisiae, histone H3 lysine 56 acetylation (H3K56ac) occurs in newly synthesized histones that are deposited throughout the genome during DNA replication. Defects in H3K56ac sensitize cells to genotoxic agents, suggesting that this modification plays an important role in the DNA damage response. However, the links between histone acetylation, the nascent chromatin structure, and the DNA damage response are poorly understood. Here we report that cells devoid of H3K56ac are sensitive to DNA damage sustained during transient exposure to methyl methanesulfonate (MMS) or camptothecin but are only mildly affected by hydroxyurea. We demonstrate that, after exposure to MMS, H3K56ac-deficient cells cannot complete DNA replication and eventually segregate chromosomes with intranuclear foci containing the recombination protein Rad52. In addition, we provide evidence that these phenotypes are not due to defects in base excision repair, defects in DNA damage tolerance, or a lack of Rad51 loading at sites of DNA damage. Our results argue that the acute sensitivity of H3K56ac-deficient cells to MMS and camptothecin stems from a failure to complete the repair of specific types of DNA lesions by recombination and/or from defects in the completion of DNA replication.     

Virulence attenuation of <Emphasis Type="Italic">Streptococcus pneumoniae clpP</Emphasis> mutant by sensitivity to oxidative stress in macrophages via an NO-mediated pathway

ClpP protease is essential for virulence and survival under stress conditions in several pathogenic bacteria. The clpP mutation in a murine infection model has demonstrated both attenuation of virulence and a sensitivity to hydrogen peroxide. However, the underlying mechanisms for these changes have not been resolved. Because macrophages play a major role in immune response and activated macrophages can kill microbes via oxygen-dependant mechanisms, we investigated the effect of the clpP mutation on its sensitivity to macrophage-mediated oxygen-dependant mechanisms. The clpP mutant derived from D39 (serotype 2) exhibited a higher sensitivity to oxidative stresses such as reactive oxygen intermediates, reactive nitrogen intermediates, and H₂O₂, but no sensitivity to osmotic stress (NaCl) and pH. Moreover, viability of the clpP mutant was significantly increased in murine macrophage cells by treatment with S-methylisothiourea sulfate, which inhibits inducible nitric oxide synthase (iNOS) activity and subsequently elicits lower level secretions of nitric oxide (NO). However, viability of wild type was unchanged. Taken together, these results indicate that ClpP is involved in the resistance to oxidative stresses after entrapment by macrophages and subsequently contributes to virulence via NO mediated pathway.