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1.
Protein Kinase PKR Mediates the Apoptosis Induction and Growth Restriction Phenotypes of C Protein-Deficient Measles Virus 总被引:1,自引:0,他引:1 下载免费PDF全文
Ann M. Toth Patricia Devaux Roberto Cattaneo Charles E. Samuel 《Journal of virology》2009,83(2):961-968
The measles virus (MV) accessory proteins V and C play important roles in MV replication and pathogenesis. Infection with recombinant MV lacking either V or C causes more cell death than infection with the parental vaccine-equivalent virus (MVvac), and C-deficient virus grows poorly relative to the parental virus. Here, we show that a major effector of the C phenotype is the RNA-dependent protein kinase PKR. Using human HeLa cells stably deficient in PKR as a result of RNA interference-mediated knockdown (PKRkd cells), we demonstrated that a reduction in PKR partially rescued the growth defect of C knockout (Cko) virus but had no effect on the growth of either wild-type (WT) or V knockout (Vko) virus. Increased growth of the Cko virus in PKRkd cells correlated with increased viral protein expression, while defective growth and decreased protein expression in PKR-sufficient cells correlated with increased phosphorylation of PKR and the α subunit of eukaryotic initiation factor 2. Furthermore, infection with WT, Vko, or especially Cko virus caused significantly less apoptosis in PKRkd cells than in PKR-sufficient cells. Although apoptosis induced by Cko virus infection in PKR-sufficient cells was blocked by a caspase antagonist, the growth of Cko virus was not restored to the WT level by treatment with this pharmacologic inhibitor. Taken together, these results indicate that PKR plays an important antiviral role during MV infection but that the virus growth restriction by PKR is not dependent upon the induction of apoptosis. Furthermore, the results establish that a principal function of the MV C protein is to antagonize the proapoptotic and antiviral activities of PKR. 相似文献
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John G. Neuhoff Katherine L. Long Rebecca C. Worthington 《Evolution and human behavior》2012,33(4):318-322
Listeners consistently perceive approaching sounds to be closer than they actually are and perceptually underestimate the time to arrival of looming sound sources. In a natural environment, this underestimation results in more time than expected to evade or engage the source and affords a “margin of safety” that may provide a selective advantage. However, a key component in the proposed evolutionary origins of the perceptual bias is the appropriate timing of anticipatory motor behaviors. Here we show that listeners with poorer physical fitness respond sooner to looming sounds and with a larger margin of safety than listeners with better physical fitness. The anticipatory perceptual bias for looming sounds is negatively correlated with physical strength and positively correlated with recovery heart rate (a measure of aerobic fitness). The results suggest that the auditory perception of looming sounds may be modulated by the response capacity of the motor system. 相似文献
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Myelography using pantopaque in greater than usual amount with a variation in technique, which is described, is believed to provide increased accuracy in differential diagnosis and precise localization of lesions in the lumbar spine. The need for multiple space exploration is eliminated and more detailed information concerning the size and shape of lesions is provided as compared to that secured by the use of 3 or 6 cc. of opaque medium and fluoroscopic examination alone. In 53 cases in which lumbar myelography was performed and the diagnosis verified or disproved at operation, there was a 5 per cent diagnostic error in 41 instances in which the method outlined was used, as compared with 17 per cent error in 12 cases in which only 3 or 6 cc. of radiopaque material and fluoroscopy alone were used. The accuracy of the procedure would appear to warrant its use in the evaluation of patients suspected of having abnormalities of the lumbar discs associated with nerve root compression. 相似文献
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Combining experimental evolution with whole‐genome resequencing is a promising new strategy for investigating the dynamics of evolutionary change. Published studies that have resequenced laboratory‐selected populations of sexual organisms have typically focused on populations sampled at the end of an evolution experiment. These studies have attempted to associate particular alleles with phenotypic change and attempted to distinguish between different theoretical models of adaptation. However, neither the population used to initiate the experiment nor multiple time points sampled during the evolutionary trajectory are generally available for examination. In this issue of Molecular Ecology, Orozco‐terWengel et al. (2012) take a significant step forward by estimating genome‐wide allele frequencies at the start, 15 generations into and at the end of a 37‐generation Drosophila experimental evolution study. The authors identify regions of the genome that have responded to laboratory selection and describe the temporal dynamics of allele frequency change. They identify two common trajectories for putatively adaptive alleles: alleles either gradually increase in frequency throughout the entire 37 generations or alleles plateau at a new frequency by generation 15. The identification of complex trajectories of alleles under selection contributes to a growing body of literature suggesting that simple models of adaptation, whereby beneficial alleles arise and increase in frequency unimpeded until they become fixed, may not adequately describe short‐term response to selection. 相似文献
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Charles L. Nunn Peter H. Thrall Kelly Stewart Alexander H. Harcourt 《Evolutionary ecology》2008,22(4):519-543
Emerging infectious diseases threaten a wide diversity of animals, and important questions remain concerning disease emergence
in socially structured populations. We developed a spatially explicit simulation model to investigate whether—and under what
conditions—disease-related mortality can impact rates of pathogen spread in populations of polygynous groups. Specifically,
we investigated whether pathogen-mediated dispersal (PMD) can occur when females disperse after the resident male dies from
disease, thus carrying infections to new groups. We also examined the effects of incubation period and virulence, host mortality
and rates of background dispersal, and we used the model to investigate the spread of the virus responsible for Ebola hemorrhagic
fever, which currently is devastating African ape populations. Output was analyzed using regression trees, which enable exploration
of hierarchical and non-linear relationships. Analyses revealed that the incidence of disease in single-male (polygynous)
groups was significantly greater for those groups containing an average of more than six females, while the total number of
infected hosts in the population was most sensitive to the number of females per group. Thus, as expected, PMD occurs in polygynous
groups and its effects increase as harem size (the number of females) increases. Simulation output further indicated that
population-level effects of Ebola are likely to differ among multi-male–multi-female chimpanzees and polygynous gorillas,
with larger overall numbers of chimpanzees infected, but more gorilla groups becoming infected due to increased dispersal
when the resident male dies. Collectively, our results highlight the importance of social system on the spread of disease
in wild mammals. 相似文献
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Using the fluorescent anion 8-anilino-1-naphthalenesulphonate (ANS) for determining the membrane surface potential necessitates that the intrinsic affinity constant Ki for the ANS sites be known. Two methods are presented which do not rely on a determination of Ki at high ionic strength. They are respectively applied to neutral membranes (egg phosphatidylcholine liposomes) and highly charged natural ones (horse bean microsomes and liposomes from their phospholipids). The value of Ki appears to be insensitive to the level of occupancy of the sites, the KCl concentration and the pH in large ranges. Furthermore, the classical Gouy-Chapman model seems to describe correctly the whole set of data, provided apparent mean molecular areas larger than the published crystallographic ones are admitted. 相似文献