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91.
Kedzierska K Thomas PG Venturi V Davenport MP Doherty PC Turner SJ La Gruta NL 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(4):2556-2562
Virus-immune CD8(+) TCR repertoires specific for particular peptide-MHC class I complexes may be substantially shared between (public), or unique to, individuals (private). Because public TCRs can show reduced TdT-mediated N-region additions, we analyzed how TdT shapes the heavily public (to D(b)NP(366)) and essentially private (to D(b)PA(224)) CTL repertoires generated following influenza A virus infection of C57BL/6 (B6, H2(b)) mice. The D(b)NP(366)-specific CTL response was virtually clonal in TdT(-/-) B6 animals, with one of the three public clonotypes prominent in the wild-type (wt) response consistently dominating the TdT(-/-) set. Furthermore, this massive narrowing of TCR selection for D(b)NP(366) reduced the magnitude of D(b)NP(366)-specific CTL response in the virus-infected lung. Conversely, the D(b)PA(224)-specific responses remained comparable in both magnitude and TCR diversity within individual TdT(-/-) and wt mice. However, the extent of TCR diversity across the total population was significantly reduced, with the consequence that the normally private wt D(b)PA(224)-specific repertoire was now substantially public across the TdT(-/-) mouse population. The key finding is thus that the role of TdT in ensuring enhanced diversity and the selection of private TCR repertoires promotes optimal CD8(+) T cell immunity, both within individuals and across the species as a whole. 相似文献
92.
Venturi V Chin HY Price DA Douek DC Davenport MP 《Journal of immunology (Baltimore, Md. : 1950)》2008,181(4):2597-2609
In some epitope-specific responses, T cells bearing identical TCRs occur in many MHC-matched individuals. The sharing of public TCRs is unexpected, given the enormous potential diversity of the TCR repertoire. We have previously studied the sharing of TCR beta-chains in the CD8(+) T cell responses to two influenza epitopes in mice. Analysis of these TCRbeta repertoires suggests that, even with unbiased V(D)J recombination mechanisms, some TCRbetas can be produced more frequently than others, by a process of convergent recombination. The TCRbeta production frequency was shown to be a good predictor of the observed sharing of epitope-specific TCRbetas between mice. However, this study was limited to immune responses in an inbred population. In this study, we investigated TCRbeta sharing in CD8(+) T cell responses specific for the immunodominant Mamu-A*01-restricted Tat-SL8/TL8 and Gag-CM9 epitopes of SIV in rhesus macaques. Multiple data sets were used, comprising a total of approximately 6000 TCRbetas sampled from 20 macaques. We observed a spectrum in the number of macaques sharing epitope-specific TCRbetas in this outbred population. This spectrum of TCRbeta sharing was negatively correlated with the minimum number of nucleotide additions required to produce the sequences and strongly positively correlated with the number of observed nucleotide sequences encoding the amino acid sequences. We also found that TCRbeta sharing was correlated with the number of times, and the variety of different ways, the sequences were produced in silico via random gene recombination. Thus, convergent recombination is a major determinant of the extent of TCRbeta sharing. 相似文献
93.
Immunocytochemical localization of the urotensin-II receptor, UT, to rat and human tissues: relevance to function 总被引:1,自引:0,他引:1
We have examined whether differential expression of UT receptors in cardiovascular tissues from rats and humans may account for the diverse vascular actions reported for urotensin-II. We found UT immunoreactivity ubiquitously expressed in arterial and venous smooth muscle and cardiomyocytes in both species, however, compared to human, levels of UT immunoreactivity in rat vascular endothelial cells was below the level for detection. In rat skeletal muscle cells UT receptor localized to the sarcolemma, a pattern comparable to that for isoforms of nitric oxide synthase suggesting that urotensin-II mediated hindquarter vasodilatation may involve release of nitric oxide from skeletal muscle fibers. 相似文献
94.
95.
Nir Dover Jason R. Barash Karen K. Hill Karen W. Davenport Hazuki Teshima Gary Xie Stephen S. Arnon 《PloS one》2013,8(4)
Sanger and shotgun sequencing of Clostridium botulinum strain Af84 type Af and its botulinum neurotoxin gene (bont) clusters identified the presence of three bont gene clusters rather than the expected two. The three toxin gene clusters consisted of bont subtypes A2, F4 and F5. The bont/A2 and bont/F4 gene clusters were located within the chromosome (the latter in a novel location), while the bont/F5 toxin gene cluster was located within a large 246 kb plasmid. These findings are the first identification of a C. botulinum strain that contains three botulinum neurotoxin gene clusters. 相似文献
96.
Highly localized changes in intracellular Ca2+ concentration ([Ca2+]i) can be evoked in neuronal growth cones; these are followed by local changes in filopodia. Focally applied electric fields evoked spatially restricted, high magnitude increases in growth cone [Ca2+]i. The earliest and greatest increases were localized to small regions within a growth cone. Such fields also produced characteristic changes in the disposition of filopodia: both filopodial length and number were significantly increased on the cathode side of growth cones. The requirement for extracellular Ca2+ and the strong correlation between the evoked rise in [Ca2+]i and the changes in filopodia (r = 0.98) indicate that cathode stimulation results in local Ca2+ influx, leading to locally increased [Ca2+]i and local changes in filopodial behavior. 相似文献
97.
Core Hunter: an algorithm for sampling genetic resources based on multiple genetic measures 总被引:1,自引:0,他引:1
Chris Thachuk José Crossa Jorge Franco Susanne Dreisigacker Marilyn Warburton Guy F Davenport 《BMC bioinformatics》2009,10(1):243
Background
Existing algorithms and methods for forming diverse core subsets currently address either allele representativeness (breeder's preference) or allele richness (taxonomist's preference). The main objective of this paper is to propose a powerful yet flexible algorithm capable of selecting core subsets that have high average genetic distance between accessions, or rich genetic diversity overall, or a combination of both. 相似文献98.
A simple inoculating loop support is described which frees both hands for other operations or permits the use of two loops. 相似文献
99.
100.
Impaired cognitive functioning in alcoholics is widespread during the first months of detoxification. Between half and two thirds of abstinent alcoholics exhibit cognitive impairments during this period, with residual deficits persisting for years after detoxification in some patients. The most severe deficits have been observed in visuospatial abilities, perceptual-motor integration, abstract reasoning, and new learning. The most significant predictors of cognitive dysfunction in persons recovering from alcoholism are the time elapsed since the last drink and the person''s age. Surprisingly, the pattern and duration of a patient''s alcohol abuse are relatively weak determinants of neuropsychological impairment during abstinence. Research investigating the hypothesis that cognitive impairments may be related to alcoholic persons resuming drinking has yielded mixed results, but a higher level of neuropsychological functioning is associated with increased rates of completing treatment programs and with greater success in the work environment after discharge from treatment. The possibility of cognitive limitations should be taken into account in planning treatment programs for alcoholism. 相似文献