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101.
HIV-1 superinfection despite broad CD8+ T-cell responses containing replication of the primary virus 总被引:21,自引:0,他引:21
Altfeld M Allen TM Yu XG Johnston MN Agrawal D Korber BT Montefiori DC O'Connor DH Davis BT Lee PK Maier EL Harlow J Goulder PJ Brander C Rosenberg ES Walker BD 《Nature》2002,420(6914):434-439
Early treatment of acute HIV-1 infection followed by treatment interruptions has shown promise for enhancing immune control of infection. A subsequent loss of control, however, allows the correlates of protective immunity to be assessed. Here we show that sudden breakthrough of plasma viraemia occurred after prolonged immune containment in an individual infected with HIV-1 at a time when 25 distinct CD8+ T-cell epitopes in the viral proteins Gag, RT, Integrase, Env, Nef, Vpr, Vif and Rev were being targeted. Sequencing of the virus in plasma and cells showed that superinfection with a second clade-B virus was coincident with the loss of immune control. This sudden increase in viraemia was associated with a decline in half of the CD8+ T-cell responses. The declining CD8+ T-cell responses were coupled with sequence changes relative to the initial virus that resulted in impaired recognition. Our data show that HIV-1 superinfection can occur in the setting of a strong and broadly directed virus-specific CD8+ T-cell response. The lack of cross-protective immunity for closely related HIV-1 strains, despite persistent recognition of multiple CD8 epitopes, has important implications for public health and vaccine development. 相似文献
102.
Instrumental observations and reconstructions of global and hemispheric temperature evolution reveal a pronounced warming during the past approximately 150 years. One expression of this warming is the observed increase in the occurrence of heatwaves. Conceptually this increase is understood as a shift of the statistical distribution towards warmer temperatures, while changes in the width of the distribution are often considered small. Here we show that this framework fails to explain the record-breaking central European summer temperatures in 2003, although it is consistent with observations from previous years. We find that an event like that of summer 2003 is statistically extremely unlikely, even when the observed warming is taken into account. We propose that a regime with an increased variability of temperatures (in addition to increases in mean temperature) may be able to account for summer 2003. To test this proposal, we simulate possible future European climate with a regional climate model in a scenario with increased atmospheric greenhouse-gas concentrations, and find that temperature variability increases by up to 100%, with maximum changes in central and eastern Europe. 相似文献
103.
In the Northern Hemisphere, ozone levels in the troposphere have increased by 35 per cent over the past century, with detrimental impacts on forest and agricultural productivity, even when forest productivity has been stimulated by increased carbon dioxide levels. In addition to reducing productivity, increased tropospheric ozone levels could alter terrestrial carbon cycling by lowering the quantity and quality of carbon inputs to soils. However, the influence of elevated ozone levels on soil carbon formation and decomposition are unknown. Here we examine the effects of elevated ozone levels on the formation rates of total and decay-resistant acid-insoluble soil carbon under conditions of elevated carbon dioxide levels in experimental aspen (Populus tremuloides) stands and mixed aspen-birch (Betula papyrifera) stands. With ambient concentrations of ozone and carbon dioxide both raised by 50 per cent, we find that the formation rates of total and acid-insoluble soil carbon are reduced by 50 per cent relative to the amounts entering the soil when the forests were exposed to increased carbon dioxide alone. Our results suggest that, in a world with elevated atmospheric carbon dioxide concentrations, global-scale reductions in plant productivity due to elevated ozone levels will also lower soil carbon formation rates significantly. 相似文献
104.
Hjorth J Watson D Fynbo JP Price PA Jensen BL Jørgensen UG Kubas D Gorosabel J Jakobsson P Sollerman J Pedersen K Kouveliotou C 《Nature》2005,437(7060):859-861
It has long been known that there are two classes of gamma-ray bursts (GRBs), mainly distinguished by their durations. The breakthrough in our understanding of long-duration GRBs (those lasting more than approximately 2 s), which ultimately linked them with energetic type Ic supernovae, came from the discovery of their long-lived X-ray and optical 'afterglows', when precise and rapid localizations of the sources could finally be obtained. X-ray localizations have recently become available for short (duration <2 s) GRBs, which have evaded optical detection for more than 30 years. Here we report the first discovery of transient optical emission (R-band magnitude approximately 23) associated with a short burst: GRB 050709. The optical afterglow was localized with subarcsecond accuracy, and lies in the outskirts of a blue dwarf galaxy. The optical and X-ray afterglow properties 34 h after the GRB are reminiscent of the afterglows of long GRBs, which are attributable to synchrotron emission from ultrarelativistic ejecta. We did not, however, detect a supernova, as found in most nearby long GRB afterglows, which suggests a different origin for the short GRBs. 相似文献
105.
A quasar is thought to be powered by the infall of matter onto a supermassive black hole at the centre of a massive galaxy. Because the optical luminosity of quasars exceeds that of their host galaxy, disentangling the two components can be difficult. This led in the 1990s to the controversial claim of the discovery of 'naked' quasars. Since then, the connection between quasars and galaxies has been well established. Here we report the discovery of a quasar lying at the edge of a gas cloud, whose size is comparable to that of a small galaxy, but whose spectrum shows no evidence for stars. The gas in the cloud is excited by the quasar itself. If a host galaxy is present, it is at least six times fainter than would normally be expected for such a bright quasar. The quasar is interacting dynamically with a neighbouring galaxy, whose gas might be feeding the black hole. 相似文献
106.
Mechanotransduction refers to the transformation of physical forces into chemical signals. It generally involves stretch-sensitive channels or conformational change of cytoskeleton-associated proteins. Mechanotransduction is crucial for the physiology of several organs and for cell migration. The extent to which mechanical inputs contribute to development, and how they do this, remains poorly defined. Here we show that a mechanotransduction pathway operates between the body-wall muscles of Caenorhabditis elegans and the epidermis. This pathway involves, in addition to a Rac GTPase, three signalling proteins found at the hemidesmosome: p21-activated kinase (PAK-1), the adaptor GIT-1 and its partner PIX-1. The phosphorylation of intermediate filaments is one output of this pathway. Tension exerted by adjacent muscles or externally exerted mechanical pressure maintains GIT-1 at hemidesmosomes and stimulates PAK-1 activity through PIX-1 and Rac. This pathway promotes the maturation of a hemidesmosome into a junction that can resist mechanical stress and contributes to coordinating the morphogenesis of epidermal and muscle tissues. Our findings suggest that the C. elegans hemidesmosome is not only an attachment structure, but also a mechanosensor that responds to tension by triggering signalling processes. We suggest that similar pathways could promote epithelial morphogenesis or wound healing in other organisms in which epithelial cells adhere to tension-generating contractile cells. 相似文献
107.
Molecular portraits of human breast tumours 总被引:181,自引:0,他引:181
108.
Bacterial growth and primary production along a north-south transect of the Atlantic Ocean 总被引:3,自引:0,他引:3
The oceanic carbon cycle is mainly determined by the combined activities of bacteria and phytoplankton, but the interdependence of climate, the carbon cycle and the microbes is not well understood. To elucidate this interdependence, we performed high-frequency sampling of sea water along a north-south transect of the Atlantic Ocean. Here we report that the interaction of bacteria and phytoplankton is closely related to the meridional profile of water temperature, a variable directly dependent on climate. Water temperature was positively correlated with the ratio of bacterial production to primary production, and, more strongly, with the ratio of bacterial carbon demand to primary production. In warm latitudes (25 degrees N to 30 degrees S), we observed alternating patches of predominantly heterotrophic and autotrophic community metabolism. The calculated regression lines (for data north and south of the Equator) between temperature and the ratio of bacterial production to primary production give a maximum value for this ratio of 40% in the oligotrophic equatorial regions. Taking into account a bacterial growth efficiency of 30%, the resulting area of net heterotrophy (where the bacterial carbon demand for growth plus respiration exceeds phytoplankton carbon fixation) expands from 8 degrees N (27 degrees C) to 20 degrees S (23 degrees C). This suggests an output of CO2 from parts of the ocean to the atmosphere. 相似文献
109.
Crumbs, the Drosophila homologue of human CRB1/RP12, is essential for photoreceptor morphogenesis 总被引:3,自引:0,他引:3
The apical transmembrane protein Crumbs is a central regulator of epithelial apical-basal polarity in Drosophila. Loss-of-function mutations in the human homologue of Crumbs, CRB1 (RP12), cause recessive retinal dystrophies, including retinitis pigmentosa. Here we show that Crumbs and CRB1 localize to corresponding subdomains of the photoreceptor apical plasma membrane: the stalk of the Drosophila photoreceptor and the inner segment of mammalian photoreceptors. These subdomains support the morphogenesis and orientation of the photosensitive membrane organelles: rhabdomeres and outer segments, respectively. Drosophila Crumbs is required to maintain zonula adherens integrity during the rapid apical membrane expansion that builds the rhabdomere. Crumbs also regulates stalk development by stabilizing the membrane-associated spectrin cytoskeleton, a function mechanistically distinct from its role in epithelial apical-basal polarity. We propose that Crumbs is a central component of a molecular scaffold that controls zonula adherens assembly and defines the stalk as an apical membrane subdomain. Defects in such scaffolds may contribute to human CRB1-related retinal dystrophies. 相似文献
110.
Most of the world's cod (Gadus morhua) fisheries are now tightly regulated or closed altogether. Being able to link individual fish to their population of origin would assist enormously in policing regulations and in identifying poachers. Here we show that microsatellite genetic markers can be used to assign individual cod from three different populations in the northeastern Atlantic Ocean to their population of origin. 相似文献