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971.
Kiepiela P Leslie AJ Honeyborne I Ramduth D Thobakgale C Chetty S Rathnavalu P Moore C Pfafferott KJ Hilton L Zimbwa P Moore S Allen T Brander C Addo MM Altfeld M James I Mallal S Bunce M Barber LD Szinger J Day C Klenerman P Mullins J Korber B Coovadia HM Walker BD Goulder PJ 《Nature》2004,432(7018):769-775
The extreme polymorphism in the human leukocyte antigen (HLA) class I region of the human genome is suggested to provide an advantage in pathogen defence mediated by CD8+ T cells. HLA class I molecules present pathogen-derived peptides on the surface of infected cells for recognition by CD8+ T cells. However, the relative contributions of HLA-A and -B alleles have not been evaluated. We performed a comprehensive analysis of the class I restricted CD8+ T-cell responses against human immunodeficiency virus (HIV-1), immune control of which is dependent upon virus-specific CD8+ T-cell activity. In 375 HIV-1-infected study subjects from southern Africa, a significantly greater number of CD8+ T-cell responses are HLA-B-restricted, compared to HLA-A (2.5-fold; P = 0.0033). Here we show that variation in viral set-point, in absolute CD4 count and, by inference, in rate of disease progression in the cohort, is strongly associated with particular HLA-B but not HLA-A allele expression (P < 0.0001 and P = 0.91, respectively). Moreover, substantially greater selection pressure is imposed on HIV-1 by HLA-B alleles than by HLA-A (4.4-fold, P = 0.0003). These data indicate that the principal focus of HIV-specific activity is at the HLA-B locus. Furthermore, HLA-B gene frequencies in the population are those likely to be most influenced by HIV disease, consistent with the observation that B alleles evolve more rapidly than A alleles. The dominant involvement of HLA-B in influencing HIV disease outcome is of specific relevance to the direction of HIV research and to vaccine design. 相似文献
972.
Jaffe W Meisenheimer K Röttgering HJ Leinert Ch Richichi A Chesneau O Fraix-Burnet D Glazenborg-Kluttig A Granato GL Graser U Heijligers B Köhler R Malbet F Miley GK Paresce F Pel JW Perrin G Przygodda F Schoeller M Sol H Waters LB Weigelt G Woillez J De Zeeuw PT 《Nature》2004,429(6987):47-49
Active galactic nuclei (AGNs) display many energetic phenomena--broad emission lines, X-rays, relativistic jets, radio lobes--originating from matter falling onto a supermassive black hole. It is widely accepted that orientation effects play a major role in explaining the observational appearance of AGNs. Seen from certain directions, circum-nuclear dust clouds would block our view of the central powerhouse. Indirect evidence suggests that the dust clouds form a parsec-sized torus-shaped distribution. This explanation, however, remains unproved, as even the largest telescopes have not been able to resolve the dust structures. Here we report interferometric mid-infrared observations that spatially resolve these structures in the galaxy NGC 1068. The observations reveal warm (320 K) dust in a structure 2.1 parsec thick and 3.4 parsec in diameter, surrounding a smaller hot structure. As such a configuration of dust clouds would collapse in a time much shorter than the active phase of the AGN, this observation requires a continual input of kinetic energy to the cloud system from a source coexistent with the AGN. 相似文献
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974.
Riassunto È stato dimostrato che la transulfurazione che consegue alla incubazione dei solfinati con zolfo ed un composto tiolico è dovuta in parte alla produzione di un polisolfuro organico, formato dal tiolo e zolfo, ed in parte al polisolfuro inorganico, formato dalla decomposizione di quello organico. L'entità della transulfurazione prodotta direttamente dal polisolfuro organico varia con il tipo di polisolfuro e dipende dalla sua stabilità nelle condizioni usate. 相似文献
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Defective viral particles and viral disease processes 总被引:94,自引:0,他引:94
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