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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
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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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A particularly vexing phenomenon within invasion ecology is the occurrence of spontaneous collapses within seemingly well-established exotic populations. Here, we assess the frequency of collapses among 68 exotic bird populations established in Hawaii, Puerto Rico, Los Angeles and Miami. Following other published definitions, we define a ‘collapse’ as a decline in abundance of ≥90 % within ≤10 years that lasts for at least 3 years. We show that 44 of the 68 exotic bird populations have exhibited declines at some point within their time series. Sixteen of the populations declined sufficiently to be defined as collapsed. It took on average 3.8 ± 1.8 years for populations to decline into a collapsed state, and this state persisted on average for 7.1 ± 6.3 years across (collapsed) populations. We compared the severity and duration of declines across all 44 declining populations according to taxonomic Order and geographic region. Neither variable explained substantial variation in the metrics of collapse. Our results indicate that severe, rapid, and persistent population declines may be common among exotic populations. We suggest that incorporating the probability and persistence of collapses into management decisions can inform efforts to enact control or eradication measures. We also suggest that applying our approach to other taxa and locations is crucial for improving our understanding of when and where collapses are likely to occur. 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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Julie K. De Zutter Kara B. Levine Di Deng Anthony Carruthers 《The Journal of biological chemistry》2013,288(28):20734-20744
The human blood-brain barrier glucose transport protein (GLUT1) forms homodimers and homotetramers in detergent micelles and in cell membranes, where the GLUT1 oligomeric state determines GLUT1 transport behavior. GLUT1 and the neuronal glucose transporter GLUT3 do not form heterocomplexes in human embryonic kidney 293 (HEK293) cells as judged by co-immunoprecipitation assays. Using homology-scanning mutagenesis in which GLUT1 domains are substituted with equivalent GLUT3 domains and vice versa, we show that GLUT1 transmembrane helix 9 (TM9) is necessary for optimal association of GLUT1-GLUT3 chimeras with parental GLUT1 in HEK cells. GLUT1 TMs 2, 5, 8, and 11 also contribute to a less abundant heterocomplex. Cell surface GLUT1 and GLUT3 containing GLUT1 TM9 are 4-fold more catalytically active than GLUT3 and GLUT1 containing GLUT3 TM9. GLUT1 and GLUT3 display allosteric transport behavior. Size exclusion chromatography of detergent solubilized, purified GLUT1 resolves GLUT1/lipid/detergent micelles as 6- and 10-nm Stokes radius particles, which correspond to GLUT1 dimers and tetramers, respectively. Studies with GLUTs expressed in and solubilized from HEK cells show that HEK cell GLUT1 resolves as 6- and 10-nm Stokes radius particles, whereas GLUT3 resolves as a 6-nm particle. Substitution of GLUT3 TM9 with GLUT1 TM9 causes chimeric GLUT3 to resolve as 6- and 10-nm Stokes radius particles. Substitution of GLUT1 TM9 with GLUT3 TM9 causes chimeric GLUT1 to resolve as a mixture of 6- and 4-nm particles. We discuss these findings in the context of determinants of GLUT oligomeric structure and transport function. 相似文献
8.
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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E. Charles Kerr E Bruce Eaton L. Thomas Netzel 《Nucleosides, nucleotides & nucleic acids》2013,32(5-6):851-866
Abstract Syntheses of two analogs of deoxyuridine with N,N-dialkylaniline chromophores are reported. 5-[3-(N-methylphenylamino)propanoyl]-2′-deoxyuridine (1) and 5-[2-(4-N,N-dimethylaminophenyl)ethyl)]-2′-deoxyuridine (2) are prepared by palladium-mediated coupling. Preparation of 2 was facilitated by in situ transient O4-trimethylsilyl protection during alkynylation which suppressed secondary cyclization of the coupling adduct. 相似文献