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991.
Nonstructural protein precursor NS4A/B from hepatitis C virus alters function and ultrastructure of host secretory apparatus 总被引:6,自引:0,他引:6
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The nonstructural proteins of hepatitis C virus (HCV) have been shown previously to localize to the endoplasmic reticulum (ER) when expressed singly or in the context of other HCV proteins. To determine whether the expression of HCV nonstructural proteins alters ER function, we tested the effect of expression of NS2/3/4A, NS4A, NS4B, NS4A/B, NS4B/5A, NS5A, and NS5B from genotype 1b HCV on anterograde traffic from the ER to the Golgi apparatus. Only the nominal precursor protein NS4A/B affected the rate of ER-to-Golgi traffic, slowing the rate of Golgi-specific modification of the vesicular stomatitis virus G protein expressed by transfection by approximately threefold. This inhibition of ER-to-Golgi traffic was not observed upon expression of the processed proteins NS4A and NS4B, singly or in combination. To determine whether secretion of other cargo proteins was inhibited by NS4A/B expression, we monitored the appearance of newly synthesized proteins on the cell surface in the presence and absence of NS4A/B expression; levels of all were reduced in the presence of NS4A/B. This reduction is also seen in cells that contain genome length HCV replicons: the rate of appearance of major histocompatibility complex class I (MHC-I) on the cell surface was reduced by three- to fivefold compared to that for a cured cell line. The inhibition of protein secretion caused by NS4A/B does not correlate with the ultrastructural changes leading to the formation a "membranous web" (D. Egger et al., J. Virol. 76:5974-5984, 2002), which can be caused by expression of NS4B alone. Inhibition of global ER-to-Golgi traffic could, by reducing cytokine secretion, MHC-I presentation, and transport of labile membrane proteins to the cell surface, have significant effects on the host immune response to HCV infection. 相似文献
992.
Jaspersen SL Huneycutt BJ Giddings TH Resing KA Ahn NG Winey M 《Developmental cell》2004,7(2):263-274
Duplication of the Saccharomyces cerevisiae spindle pole body (SPB) once per cell cycle is essential for bipolar spindle formation and accurate chromosome segregation during mitosis. We have investigated the role that the major yeast cyclin-dependent kinase Cdc28/Cdk1 plays in assembly of a core SPB component, Spc42, to better understand how SPB duplication is coordinated with cell cycle progression. Cdc28 is required for SPB duplication and Spc42 assembly, and we found that Cdc28 directly phosphorylates Spc42 to promote its assembly into the SPB. The Mps1 kinase, previously shown to regulate Spc42 phosphorylation and assembly, is also a Cdc28 substrate, and Cdc28 phosphorylation of Mps1 is needed to maintain wild-type levels of Mps1 in cells. Analysis of nonphosphorylatable mutants in SPC42 and MPS1 indicates that direct Spc42 phosphorylation and indirect regulation of Spc42 through Mps1 are two overlapping pathways by which Cdc28 regulates Spc42 assembly and SPB duplication during the cell cycle. 相似文献
993.
Mps3p is a novel component of the yeast spindle pole body that interacts with the yeast centrin homologue Cdc31p 总被引:2,自引:0,他引:2
Accurate duplication of the Saccharomyces cerevisiae spindle pole body (SPB) is required for formation of a bipolar mitotic spindle. We identified mutants in SPB assembly by screening a temperature-sensitive collection of yeast for defects in SPB incorporation of a fluorescently marked integral SPB component, Spc42p. One SPB assembly mutant contained a mutation in a previously uncharacterized open reading frame that we call MPS3 (for monopolar spindle). mps3-1 mutants arrest in mitosis with monopolar spindles at the nonpermissive temperature, suggesting a defect in SPB duplication. Execution point experiments revealed that MPS3 function is required for the first step of SPB duplication in G1. Like cells containing mutations in two other genes required for this step of SPB duplication (CDC31 and KAR1), mps3-1 mutants arrest with a single unduplicated SPB that lacks an associated half-bridge. MPS3 encodes an essential integral membrane protein that localizes to the SPB half-bridge. Genetic interactions between MPS3 and CDC31 and binding of Cdc31p to Mps3p in vitro, as well as the fact that Cdc31p localization to the SPB is partially dependent on Mps3p function, suggest that one function for Mps3p during SPB duplication is to recruit Cdc31p, the yeast centrin homologue, to the half-bridge. 相似文献
994.
Artificial neural network prediction of antisense oligodeoxynucleotide activity 总被引:3,自引:1,他引:2
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Giddings MC Shah AA Freier S Atkins JF Gesteland RF Matveeva OV 《Nucleic acids research》2002,30(19):4295-4304
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G. D. Giddings N. R. Sackville Hamilton M. D. Hayward 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1997,94(8):1007-1014
In part 1 an experiment was described for determining the extent of pollen dispersal from a Lolium source. The results were used to test Bateman’s pollen dispersal equations, which were found to be not particularly useful
for describing variation in pollen deposition with distance. An improvement is suggested here which takes the influence of
wind direction into account. For 11 of the 12 datasets the new equations fit significantly better than the original ones.
Mean wind directions were used to produce 15 data subsets for testing Bateman’s equations for dispersal downwind of a pollen
source. These equations fitted only 4 of the data subsets, all of which were collected from traps facing towards the pollen
source. The usefulness of the model equations in estimating the importance of turbulence is brought into question. It is shown
that models incorporating only distance and wind direction do not accurately describe pollen deposition. The amount of pollen
deposited does not always decrease smoothly with increasing distance from the source. The variation in the amount of pollen
deposited is probably influenced by several factors, including wind speed and turbulence.
Received: 5 June 1996 / Accepted: 11 October 1996 相似文献
1000.
Tadarida pumila exhibits post-partum oestrus in the sub-tropical latitudes of Southern Africa. Females nursing their first young of the season were either pregnant or had large Graafian follicles in their right ovaries. Further evidence that ovulation occurs soon after parturition was found in the ovaries, where follicles were developing alongside the corpora lutea of pregnancy. The latter indicates that oestrus occurs following parturition. Furthermore, as opposed to the first pregnancy of the season, the development of the endometrium was found to be less complete in the two subsequent pregnancies of that particular season. This is interpreted as being related to the very short interval between parturition and the following conception. 相似文献