Chronic hepatitis B virus (HBV) infection is a major cause of liver disease. Only interferon-alpha and the nucleosidic inhibitors of the viral polymerase, 3TC and adefovir, are approved for therapy. However, these therapies are limited by the side effects of interferon and the substantial resistance of the virus to nucleosidic inhibitors. Potent new antiviral compounds suitable for monotherapy or combination therapy are highly desired. We describe non-nucleosidic inhibitors of HBV nucleocapsid maturation that possess in vitro and in vivo antiviral activity. These inhibitors have potential for future therapeutic regimens to combat chronic HBV infection. 相似文献
Catalytic antibody technology has been used to explore the contribution of medium effects to the overall rate of an enzyme-catalyzed reaction. An antibody generated against a derivative of 2-acetamido-1,5-napthalenedisulfonate efficiently catalyzes the decarboxylation of 5-nitro-3-carboxybenzisoxazole. This unimolecular reaction is not susceptible to general acid-base catalysis but is highly sensitive to microenvironment; thus, it provides a simple chemical model for biologically important decarboxylations. The 10(4)-fold rate acceleration observed for the antibody reflects the kinetic advantage of the low-dielectric environment of the binding pocket acting to destabilize the substrate by desolvation and to stabilize the charge-delocalized transition state through dispersion interactions. These results are pertinent to an understanding of solvent effects in enzymic reactions in general and suggest approaches for developing antibody catalysts for numerous other reactions that involve large changes in charge distribution as the reaction coordinate is traversed. 相似文献
Plants generate effective responses to infection by recognizing both conserved and variable pathogen-encoded molecules. Pathogens deploy virulence effector proteins into host cells, where they interact physically with host proteins to modulate defense. We generated an interaction network of plant-pathogen effectors from two pathogens spanning the eukaryote-eubacteria divergence, three classes of Arabidopsis immune system proteins, and ~8000 other Arabidopsis proteins. We noted convergence of effectors onto highly interconnected host proteins and indirect, rather than direct, connections between effectors and plant immune receptors. We demonstrated plant immune system functions for 15 of 17 tested host proteins that interact with effectors from both pathogens. Thus, pathogens from different kingdoms deploy independently evolved virulence proteins that interact with a limited set of highly connected cellular hubs to facilitate their diverse life-cycle strategies. 相似文献
In this study, effects of different sowing dates and seeding rates on N uptake efficiency (NUE), N translocation efficiency (NTE), agronomic efficiency (AE), physiological efficiency (PE), water use efficiency for grain yield (WUEg) and water use efficiency for biomass (WUEb) of facultative wheat were investigated. As the average of cropping year, sowing dates and seeding rates, N uptake efficiency (NUE), N translocation efficiency (NTE), agronomic efficiency (AE), physiological efficiency (PE), water use efficiency for grain yield (WUEg) and water use efficiency for biomass (WUEb) values were respectively obtained as 1.17?kg Nuptake/kg Napplied, 68.5%, 36.9?kg grain/kg Napplied, 31.2?kg grain/kg Nuptake, 5.19?kg ha?1 mm?1 and 18.04?kg ha?1 mm?1.
Nitrogen and water use efficiencies decreased with delayed sowing dates and increased with increasing seeding rates. It is possible to maintain a high wheat yield, nitrogen and water use efficiency by increasing plant density through winter sowing. It was concluded based on present findings that sowing date and seeding rates had significant effects on nitrogen and water use efficiencies and winter sowing should be practiced as not to cause yield losses and high seeding rates (575 seeds m?2) yielded greater nitrogen-water use efficiencies.
We aimed to investigate whether sodium chloride seed priming and irrigation at seedling stage enhance response of 5-leaf stage tomato plants (Lycopersium esculentum Mill.) to high salt stress. Three experimental groups were as; non-primed seeds, seeds primed with 0.05M sodium chloride (NaCl), and seeds primed and irrigated with 0.05M NaCl starting from sowing to salt stress application. Sodium chloride solutions (0.1M, 0.2M, 0.4M, and 0.6M) were added to cups under pots in every 2 days for 10 days to treatment groups. Control groups were irrigated with distilled water at the same time intervals. At least two experimental setups contained at least four plants, and two samplings of leaf and root tissues were performed for analysis of each plant to evaluate changes in pigment and proline contents, lipid peroxidation and electrolyte leakage levels, and ascorbate peroxidase and catalase activity. Priming reduced mean germination time, and increased final germination percentage together with energy of germination. Increased root and hypocotyl lengths as well as increases in fresh weights supported enhanced seedling vigor. Considering growth and stress parameters such as chlorophyll content, chlorophyll to carotenoid ratios, and lipid peroxidation and electrolyte leakage were less affected in primed plants. Moreover, improvement of the accumulation of osmoregulating defense molecules, such as proline and anthocyanin, and of the inductions of the antioxidative enzyme system points out to higher adaptive response of these plants against deleterious effects of salt. 相似文献
INTRODUCTION: The International Physical Activity Questionnaire (IPAQ) was developed to measure health-related physical activity (PA) in populations. The short version of the IPAQ has been tested extensively and is now used in many international studies. The present study aimed to explore the validity characteristics of the long-version IPAQ. SUBJECTS AND METHODS: Forty-six voluntary healthy male and female subjects (age, mean +/- standard deviation: 40.7 +/- 10.3 years) participated in the study. PA indicators derived from the long, self-administered IPAQ were compared with data from an activity monitor and a PA log book for concurrent validity, and with aerobic fitness, body mass index (BMI) and percentage body fat for construct validity. RESULTS: Strong positive relationships were observed between the activity monitor data and the IPAQ data for total PA (rho = 0.55, P < 0.001) and vigorous PA (rho = 0.71, P < 0.001), but a weaker relationship for moderate PA (rho = 0.21, P = 0.051). Calculated MET-h day(-1) from the PA log book was significantly correlated with MET-h day(-1) from the IPAQ (rho = 0.67, P < 0.001). A weak correlation was observed between IPAQ data for total PA and both aerobic fitness (rho = 0.21, P = 0.051) and BMI (rho = 0.25, P = 0.009). No significant correlation was observed between percentage body fat and IPAQ variables. Bland-Altman analysis suggested that the inability of activity monitors to detect certain types of activities might introduce a source of error in criterion validation studies. CONCLUSIONS: The long, self-administered IPAQ questionnaire has acceptable validity when assessing levels and patterns of PA in healthy adults. 相似文献
Conflict over marine fishery resources is a growing security concern. Experts expect that global changes in our climate, food systems and oceans may spark or exacerbate resource conflicts. An initial scan of 803 relevant papers and subsequent intensive review of 31 fisheries conflict studies, focused on subnational and international conflicts, suggests that four substantial scientific gaps need addressing to improve our understanding of the nature and drivers of fisheries conflict. First, fisheries conflict and levels of conflict intensity are not precisely defined. Second, complex adaptive systems thinking is underutilized but has the potential to produce more realistic causal models of fishery conflict. Third, comparative large‐scale data and suitably integrative methodologies are lacking, underscoring the need for a standardized and comparable database of fisheries conflict cases to aid extrapolation beyond single case‐studies. Fourth, there is room for a more widespread application of higher order concepts and associated terminology. Importantly, the four gaps highlight the homogenized nature of current methodological and theoretical approaches to understanding fishery conflict, which potentially presents us with an oversimplified understanding of these conflicts. A more nuanced understanding of the complex and dynamic nature of fishery conflict and its causes is not only scientifically critical, but increasingly relevant for policymakers and practitioners in this turbulent world. 相似文献