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61.
To investigate the relation between protein stability and the predicted stabilities of individual secondary structural elements, residue Pro86 in an alpha-helix in phage T4 lysozyme was replaced by ten different amino acids. The x-ray crystal structures of seven of the mutant lysozymes were determined at high resolution. In each case, replacement of the proline resulted in the formation of an extended alpha-helix. This involves a large conformational change in residues 81 to 83 and smaller shifts that extend 20 angstroms across the protein surface. Unexpectedly, all ten amino acid substitutions marginally reduce protein thermostability. This insensitivity of stability to the amino acid at position 86 is not simply explained by statistical and thermodynamic criteria for helical propensity. The observed conformational changes illustrate a general mechanism by which proteins can tolerate mutations.  相似文献   
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Antigenic and genetic analysis of the hemagglutinin of approximately 13,000 human influenza A (H3N2) viruses from six continents during 2002-2007 revealed that there was continuous circulation in east and Southeast Asia (E-SE Asia) via a region-wide network of temporally overlapping epidemics and that epidemics in the temperate regions were seeded from this network each year. Seed strains generally first reached Oceania, North America, and Europe, and later South America. This evidence suggests that once A (H3N2) viruses leave E-SE Asia, they are unlikely to contribute to long-term viral evolution. If the trends observed during this period are an accurate representation of overall patterns of spread, then the antigenic characteristics of A (H3N2) viruses outside E-SE Asia may be forecast each year based on surveillance within E-SE Asia, with consequent improvements to vaccine strain selection.  相似文献   
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The antigenic evolution of influenza A (H3N2) virus was quantified and visualized from its introduction into humans in 1968 to 2003. Although there was remarkable correspondence between antigenic and genetic evolution, significant differences were observed: Antigenic evolution was more punctuated than genetic evolution, and genetic change sometimes had a disproportionately large antigenic effect. The method readily allows monitoring of antigenic differences among vaccine and circulating strains and thus estimation of the effects of vaccination. Further, this approach offers a route to predicting the relative success of emerging strains, which could be achieved by quantifying the combined effects of population level immune escape and viral fitness on strain evolution.  相似文献   
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Biopsy material taken from the brain of a patient with CreutzfeldtJakob disease with status spongiosus induced a similar fatal encephalopathy in a chimpanzee 13 months after inoculation.  相似文献   
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Vector-borne parasites cause major human diseases of the developing world, including malaria, human African trypanosomiasis, Chagas disease, leishmaniasis, filariasis, and schistosomiasis. Although the life cycles of these parasites were defined over 100 years ago, the strategies they use to optimize their successful transmission are only now being understood in molecular terms. Parasites are now known to monitor their environment in both their host and vector and in response to other parasites. This allows them to adapt their developmental cycles and to counteract any unfavorable conditions they encounter. Here, I review the interactions that parasites engage in with their hosts and vectors to maximize their survival and spread.  相似文献   
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The large variation in the ratio of uranium-234 to uranium-238 (234U/238U) in rivers is not well understood, but may provide information about past weathering and rainfall and is important because it controls seawater (234U/238U). Here, we demonstrate the importance of physical weathering and rainfall for (234U/238U), using rivers from South Island, New Zealand. These data allow interpretation of an existing speleothem (234U/238U) record and suggest that New Zealand glacier advance 13,000 years ago was influenced by increased rainfall rather than by Younger Dryas-like cooling. A model of seawater (234U/238U) during glacial cycles indicates that rejection of corals based on modern (234U/238U) +/- <0.01 is not merited and may reject the highest quality ages.  相似文献   
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BACKGROUND: Economic costs of spotted wing drosophila (SWD) include yield and associated revenue losses, labor and material costs for monitoring and management and revenue losses due to the closure of export markets should fruit from SWD‐infested regions be banned by trading partners. This analysis focuses on two types of loss in the California raspberry and strawberry industries: yield losses in the absence of management, and insecticide material costs on a per treatment basis. It computes the cost of a specific management program for raspberries in California's Central Coast region. RESULTS: Insecticide material and application costs per treatment and the cost of the management program are small relative to the yield losses in the absence of management that are observed by growers, researchers and others in initial infestations. CONCLUSION: It is difficult to evaluate precisely the share of pest management program costs due to SWD because insecticides are sometimes used to manage multiple pests, and because labor‐intensive field sanitation efforts to control SWD are recommended practices already. Given these considerations, this analysis finds that the benefits to SWD management well outweigh the costs examined here. Evaluating the efficacy of managing SWD is essential in assessing the risks that SWD poses and the benefits of pest management programs. Copyright © 2011 Society of Chemical Industry  相似文献   
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