To elucidate the relationship between ALDH2-catalyzed

GTN bioconversion and established ALDH2 activities (dehydrogenase, esterase), we compared the function of the wild type (WT) enzyme with mutants lacking either the reactive Cys-302 (C302S) or the general base Glu-268 (E268Q). Although the C302S mutation led to >90% loss of all enzyme activities, the E268Q mutant exhibited virtually unaffected rates of GTN denitration despite low dehydrogenase and esterase activities. The nucleotide co-factor NAD caused a pronounced increase in the rates of 1,2-glyceryl dinitrate formation by WT-ALDH2 but inhibited the reaction catalyzed by the E268Q mutant. GTN bioactivation measured as activation of purified soluble guanylate cyclase or release of NO in the presence of WT- or E268Q-ALDH2 was markedly DZNeP ic50 potentiated by superoxide dismutase, suggesting that bioavailability of GTN-derived NO is limited by co-generation of superoxide. Formation of superoxide was confirmed by determination of hydroethidine oxidation that was inhibited by superoxide dismutase and the ALDH2 inhibitor chloral hydrate. E268Q-ALDH2 exhibited similar to 50% lower rates of superoxide formation than the WT enzyme. Our results suggest that Glu-268 is involved in the structural organization

of the NAD-binding pocket but is not required for GTN denitration. ALDH2-catalyzed superoxide formation may essentially contribute to oxidative stress in GTN-exposed blood vessels.”
“The concept of detached concern, as proposed by Renee Fox Linsitinib in Experiment Perilous (1959), is often used in selleck chemicals the literature today in a way she did not intend. Rather than viewing detachment and concern as dualities, scholars

frequently conceive of them as dichotomous, emphasizing detachment over concern. We reconsider detached concern here through the stories 37 intensive-care nurses told about their most memorable patients. While many described efforts to keep emotionally distant from patients, they also expressed concern for patients they felt connected to, especially those who were a first for them, who were long-term primary patients, who surprised them, or who died. The care nurses provide for these patients is shaped sociologically by their training and institutional contexts and is not an aberration or indicative of their losing control of their feelings. Instead, it is evidence of the dual nature of detached concern and of the importance of viewing the concept as describing more than emotional detachment.”
“Amyloid formation is a widespread feature of various proteins. It is associated with both important diseases (including infectious mammalian prions) and biologically positive functions, and provides a basis for structural “templating” and protein-based epigenetic inheritance (for example, in the case of yeast prions). Amyloid templating is characterized by a high level of sequence specificity and conformational fidelity.