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71.
Loffredo JT Friedrich TC León EJ Stephany JJ Rodrigues DS Spencer SP Bean AT Beal DR Burwitz BJ Rudersdorf RA Wallace LT Piaskowski SM May GE Sidney J Gostick E Wilson NA Price DA Kallas EG Piontkivska H Hughes AL Sette A Watkins DI 《PloS one》2007,2(11):e1152
Background
It is generally accepted that CD8+ T cell responses play an important role in control of immunodeficiency virus replication. The association of HLA-B27 and -B57 with control of viremia supports this conclusion. However, specific correlates of viral control in individuals expressing these alleles have been difficult to define. We recently reported that transient in vivo CD8+ cell depletion in simian immunodeficiency virus (SIV)-infected elite controller (EC) macaques resulted in a brief period of viral recrudescence. SIV replication was rapidly controlled with the reappearance of CD8+ cells, implicating that these cells actively suppress viral replication in ECs.Methods and Findings
Here we show that three ECs in that study made at least seven robust CD8+ T cell responses directed against novel epitopes in Vif, Rev, and Nef restricted by the MHC class I molecule Mamu-B*08. Two of these Mamu-B*08-positive animals subsequently lost control of SIV replication. Their breakthrough virus harbored substitutions in multiple Mamu-B*08-restricted epitopes. Indeed, we found evidence for selection pressure mediated by Mamu-B*08-restricted CD8+ T cells in all of the newly identified epitopes in a cohort of chronically infected macaques.Conclusions
Together, our data suggest that Mamu-B*08-restricted CD8+ T cell responses effectively control replication of pathogenic SIVmac239. All seven regions encoding Mamu-B*08-restricted CD8+ T cell epitopes also exhibit amino acid replacements typically seen only in the presence of Mamu-B*08, suggesting that the variation we observe is indeed selected by CD8+ T cell responses. SIVmac239 infection of Indian rhesus macaques expressing Mamu-B*08 may therefore provide an animal model for understanding CD8+ T cell-mediated control of HIV replication in humans. 相似文献72.
Lissette M. Ruberté Raghu N. Natarajan Gunnar BJ. Andersson 《Journal of biomechanics》2009,42(3):341-348
The current study investigated mechanical predictors for the development of adjacent disc degeneration. A 3-D finite element model of a lumbar spine was modified to simulate two grades of degeneration at the L4–L5 disc. Degeneration was modeled by changes in geometry and material properties. All models were subjected to follower preloads of 800 N and moment loads in the three principal directions of motion using a hybrid protocol. Degeneration caused changes in the loading and motion patterns of the segments above and below the degenerated disc. At the level (L3–L4) above the degenerated disc, the motion increased due to moderate degeneration by 21% under lateral bending, 26% under axial rotation and 28% under flexion/extension. At the level (L5-S1) below the degenerated disc, motion increased only during lateral bending by 20% due to moderate degeneration. Both the L3–L4 and L5-S1 segment showed a monotonic increase in both the maximum von Mises stress and shear stress in the annulus as degeneration progressed for all loading directions, expect extension at L3–L4. The most significant increase in stress was observed at the L5-S1 level during axial rotation with nearly a ten-fold increase in the maximum shear stress and 103% increase in the maximum von Mises stress. The L5-S1 segment also showed a progressive increase in facet contact force for all loading directions with degeneration. Nucleus pressure did not increase significantly for any loading direction at either the caudal or cephalic adjacent segment. Results suggest that single-level degeneration can increase the risk for injury at the adjacent levels. 相似文献
73.
The oligomerization of a family of four genetically clustered human gastrointestinal mucins 总被引:1,自引:0,他引:1
Mucins are synthesized and secreted by many epithelia. They are complex
glycoproteins that offer cytoprotection. In their functional configuration,
mucins form oligomers by a biosynthetic process that is poorly understood.
A family of four human gastrointestinal mucin genes (MUC2, MUC5AC, MUC5B,
and MUC6) is clustered to chromosome 11p15.5. To study oligomerization of
these related mucins, we performed metabolic labeling experiments with
[35S]amino acids in LS174T cells, and isolated mucin precursors by specific
immunoprecipitations that were analyzed on SDS-PAGE. Each of the precursors
of MUC2, MUC5AC, MUC5B, and MUC6 formed a single species of
disulfide-linked homo-oligomer within 1 h after pulse labeling. Based on
apparent molecular masses, these oligomeric precursors were most likely
dimers. Inhibition of vesicular RER-to-Golgi transport, with brefeldin A
and CCCP, did not affect the dimerization of MUC2 precursors, localizing
dimerization to the RER. O-Glycosylation of MUC2 followed dimerization.
Inhibition of N- glycosylation by tunicamycin retarded, but did not
inhibit, dimerization, indicating that N-glycans play a role in efficient
dimerization of MUC2 precursors. Based on sequence homology, the ability of
MUC2, MUC5AC, MUC5B and MUC6 to dimerize most likely resides in their
C-terminal domains. Thus, the RER-localized dimerization of secretory
mucins likely proceeds by similar mechanisms, which is an essential step in
the formation of the human gastrointestinal mucus- gels.
相似文献
74.
1. Considerable evidence suggests that the diversity within plant communities may strongly affect the strength of species interactions, but the majority of studies only considered interspecific diversity. 2. This paper examines the effect of intraspecific genetic diversity within Brassica fields on two Brassica specialists, cabbage root fly, and diamondback moth, and on a parasitoid attacking diamondback moths. Genetic diversity was manipulated both in a replacement and an additive design. 3. Both herbivore densities and parasitism rates were higher in smaller plots, with limited responses to increased within‐plot diversity. All species showed variable densities across genotypes, and preference hierarchies were species specific. 4. Responses to plot size in root flies scaled with the diameter‐to‐area ratio, suggesting that patch detectability affected local density, whereas responses by diamondback moths and parasitoids deviated from this ratio. These species differences could be traced to differences in the residence time within patches, where diamondback moths typically spend longer and more variable time periods in patches than root flies. 5. The lack of response to genetic diversity by both herbivores suggests that egg‐laying rates are affected by decisions on the plant and not by attraction from a distance, neither to the plant itself nor the patch. Patterns of differential attack may then be due to different acceptability for studied genotypes. 6. Future theories on insect responses to spatial heterogeneity should focus on species traits and how traits interact with information landscapes in the field. 相似文献
75.
NELSON VALDIVIA JARROD D. STEHBENS BJÖRN HERMELINK SEAN D. CONNELL MARKUS MOLIS MARTIN WAHL 《Austral ecology》2008,33(8):951-962
Local dynamics such as resource enhancement (e.g. nutrient supply) and stochastic events of destruction (disturbances that provide new space) are hypothesized to counteractively affect species diversity and composition. We tested the independent and interactive effects of nutrients and disturbance on the development of assemblages of epibiota attached to vertical surfaces in an oligotrophic system. Nutrient concentrations were manipulated at three levels (ambient, medium and high) while disturbance was manipulated by removing biomass at seven frequencies (0×, 2×, 3×, 4×, 5×, 7×, 12×). Nutrient and disturbance regimes had opposing effects on diversity such that species richness increased with resource enhancement (nutrients) and declined with disturbance. These results support the model that increased heterogeneity of distribution of limiting resources allows the coexistence of species with low and high resource requirements. 相似文献
76.
Abstract The palatability to common carp, Cyprinus carpio L. of three newly developed differently flavoured floating pellets made from a high proportion (40%) of brewer's spent grain (BSG) was tested using a multiple-offer feeding experiment. The addition of ‘bold’ flavours, such as vanilla or strawberry essence, may help mask the unpleasant taste of some piscicides; however, their inclusion must not compromise uptake by carp. There were no significant differences between the consumption rates of the three varieties, and all flavours were readily consumed. Therefore, it is suggested that highly flavoured pellets made with BSG have a strong potential to mask the flavour of an unpalatable toxin, and further research is now needed to test this hypothesis. 相似文献
77.
Not all cytokine-producing CD8+ T cells suppress simian immunodeficiency virus replication
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Chung C Lee W Loffredo JT Burwitz B Friedrich TC Giraldo Vela JP Napoe G Rakasz EG Wilson NA Allison DB Watkins DI 《Journal of virology》2007,81(3):1517-1523
Current assays of CD8+ T-lymphocyte function measure cytokine production rather than the ability of these lymphocytes to suppress viral replication. Here we show that CD8+ T-cell clones recognizing the same epitope vary enormously in the ability to suppress simian immunodeficiency virus SIVmac239 replication in an in vitro suppression assay. However, all Nef(165-173)IW9- and Vif(66-73)HW8-specific clones from elite controllers effectively suppressed SIV replication. Interestingly, in vitro suppression efficacy was not always associated with the ability to produce gamma interferon, tumor necrosis factor alpha, or interleukin-2. 相似文献
78.
79.
Previous studies of the effect of carbonation on taste perception have
suggested that it may be negligible, manifesting primarily in increases in
the perceived intensity of weak salt and sour stimuli. Assuming CO2
solutions in the mouth stimulate only trigeminal nerve endings, this result
is not altogether surprising; however, there are neurophysiological data
indicating that CO2 stimulates gustatory as well as trigeminal fibers. In
that case, carbonation might alter the quality profile of a stimulus
without producing substantial changes in overall taste intensity--much as
occurs when qualitatively different taste stimuli are mixed. To address
this possibility, subjects were asked to rate the total taste intensity of
moderate concentrations of stimuli representing each of the basic tastes
and their binary combinations, with an without added carbonation. They then
subdivided total taste intensity into the proportions of sweetness,
saltiness, sourness, bitterness and 'other taste qualities' they perceived.
The addition of carbonation produced only small increases in ratings of
total taste intensity. However, rather dramatic alterations in the quality
profiles of stimuli were observed, particularly for sweet and salty tastes.
The nature of the interaction is consistent with a direct effect of
carbonation/CO2 on the gustatory system, although the possibility that at
least some of the observed effects reflect trigeminal-gustatory
interactions cannot be ruled out.
相似文献
80.