Deglycosylation of nucleotides occurs during many essential biological processes, including DNA repair, and is initiated by a variety of nucleophiles. In the present work, density functional theory (B3LYP) was used to investigate the thermodynamics and kinetics of the glycosidic bond cleavage reaction in the model nucleoside forms of guanine and its major oxidation product, 8-oxoguanine. Base excision facilitated by four different nucleophiles (hydroxyl anion (fully activated water), formate-water complex (partially activated water), lysine, and proline) was considered, which spans nucleophiles involved in a collection of spontaneous and enzyme-catalyzed processes. Because some enzymes that catalyze deglycosylation can accommodate more than one orientation of the base with respect to the sugar moiety, the effects of the (anti/syn) base orientation on the barrier height were also considered. We find that the nucleophile has a very large effect on the overall (gas-phase) reaction energetics. Although this effect decreases in different (polar) environments, the nucleophile has the greatest influence on the overall reaction as compared to whether the base is damaged or to the base orientation. Furthermore, the effects are significant in environments that most closely resemble (nonpolar) enzymatic active sites. Our results provide a greater understanding of the relative effects of the nucleophile, damage to the nucleobase, and the nucleobase orientation with respect to the sugar moiety on the deglycosylation pathway, which provide qualitative explanations for relative base excision rates observed in some biological systems.
The study investigated whether differences exist between postmenopausal Caucasian vegetarian and omnivorous women regarding trabecular and cortical bone density measured with single- and dual-photon absorptiometry. Anthropometric measurements, blood and urine samples, and food intakes of the twenty-eight matched pairs were also compared. The Wilcoxon signed-rank test indicated no significant differences in bone measurements between vegetarians and omnivores at any sites except the skull. The vegetarians' serum globulin and total protein measured higher. Urine calcium and creatinine were similar between the groups. The vegetarians consumed greater quantities of carbohydrate, fiber, magnesium, ascorbic acid, copper, and energy as percent carbohydrate, and lower quantities of protein, niacin, alcohol, vitamin B-12, cholesterol, and energy as percent protein. Despite several differences in dietary intakes, the results indicate that neither cortical nor trabecular bone density in these postmenopausal women was affected by a lactoovovegetarian diet.
The current results underscore the significant role of cognitive, affective, and behavioral factors in perceived physical disability and their mediated detrimental effect on physical and psychological quality of life in patients with rheumatic diseases. Implications for rehabilitation The fear-avoidance model is applicable to the prediction of quality of life in patients with rheumatic diseases. As pain-catastrophizing and fear-avoidance beliefs are important factors linked to physical disability and depression, intervening these cognitive factors is necessary to improve physical function and depression in patients with rheumatic diseases. Considering the strong association between depression and physical and psychological quality of life, the assessment and treatment of the former should be included in the rehabilitation of patients with rheumatic diseases. Interventions targeting physical function and depression are likely to be effective in terms of improving physical and psychological quality of life in patients with rheumatic diseases.
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