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International Journal of Peptide Research and Therapeutics - The growth of pathogens across the globe is developing at a very fast rate, thus turning into a worldwide health problem. Since, current...  相似文献   
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Over recent years, there has been a renewed interest in the development of l-nucleosides as safe and efficacious drugs for the treatment of viral infections. Biological activity of these compounds requires phosphorylation to their triphosphate form, involving nucleoside monophosphate kinases in the second step. In order to characterize the activation pathway of l-nucleosides of the pyrimidine series, we studied the enantio-selectivity of human uridylate-cytidylate and thymidylate kinases. The results showed that these enzymes are only weakly enantio-selective and are thus probably involved in the activation of l-nucleosides in vivo. An activation pathway for telbivudine (l-dT) was therefore proposed.  相似文献   
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Recent years have witnessed a new round of research on one of the most studied proteins - myoglobin (Mb), the oxygen (O2) carrier of skeletal and heart muscle. Two major discoveries have stimulated research in this field: 1) that Mb has additional protecting functions, such as the regulation of in vivo levels of the signaling molecule nitric oxide (NO) by scavenging and generating NO during normoxia and hypoxia, respectively; and 2) that Mb in vertebrates (particularly fish) is expressed as tissue-specific isoforms in other tissues than heart and skeletal muscle, such as vessel endothelium, liver and brain, as found in cyprinid fish. Furthermore, Mb has also been found to protect against oxidative stress after hypoxia and reoxygenation and to undergo allosteric, O2-linked S-nitrosation, as in rainbow trout. Overall, the emerging evidence, particularly from fish species, indicates that Mb fulfills a broader array of physiological functions in a wider range of different tissues than hitherto appreciated. This new knowledge helps to better understand how variations in Mb structure and function may correlate with differences in animals' lifestyles and hypoxia-tolerance. This review integrates old and new results on Mb expression patterns and functional properties amongst vertebrates and discusses how these may relate to adaptive variations in different species. This article is part of a special issue entitled: Oxygen Binding and Sensing Proteins.  相似文献   
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Many large raptors exploit or rely on anabatic and orographic winds which provide vertical lift, to supplement or provide the energy fuelling flight. Airspace is therefore a critical habitat for such large raptors and its use is subject to the underlying terrestrial topography, because particular topographical features are more likely to provide wind-energetic lift. Accordingly, ridges and/or ‘rugged topography’ are common preferred features in habitat use by large raptors. Our study aimed to provide a simple model of space use for a large raptor, the Golden Eagle Aquila chrysaetos, based on thousands of GPS telemetry records during juvenile dispersal of 92 birds tagged as nestlings between 2007 and 2016 across upland Scotland. Model development was based on the hypothesis that four topographical variables would be influential: slope, aspect, altitude and distance from ridge. The telemetry dataset was divided into training and two testing components. The first testing set was derived by a temporal split resulting in approximately equal sample size on records and some temporal overlap in individuals’ records with training data. The second testing set involved no individuals from the training set. Aspect was removed early in training model development because it was not influential. The model found that young Golden Eagles preferred, or used according to availability, space above slopes greater than 10°, at an altitude of ≥ 300 m, and within 300 m of a ridge. The test data were highly correlated with those from the training data in the model variables, and performance as regard to expected preferences from the model was improved in both test datasets, indicating the model was robust. Given the apparent universal nature of large raptor dependence on topography, that topography is relatively immutable according to time and use, and that topographical data are readily available, we commend our approach to other habitat preference studies of Golden Eagles and other large raptors elsewhere.  相似文献   
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