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151.
Antibody neutralization and escape by HIV-1 总被引:62,自引:0,他引:62
Wei X Decker JM Wang S Hui H Kappes JC Wu X Salazar-Gonzalez JF Salazar MG Kilby JM Saag MS Komarova NL Nowak MA Hahn BH Kwong PD Shaw GM 《Nature》2003,422(6929):307-312
Neutralizing antibodies (Nab) are a principal component of an effective human immune response to many pathogens, yet their role in HIV-1 infection is unclear. To gain a better understanding of this role, we examined plasma from patients with acute HIV infection. Here we report the detection of autologous Nab as early as 52 days after detection of HIV-specific antibodies. The viral inhibitory activity of Nab resulted in complete replacement of neutralization-sensitive virus by successive populations of resistant virus. Escape virus contained mutations in the env gene that were unexpectedly sparse, did not map generally to known neutralization epitopes, and involved primarily changes in N-linked glycosylation. This pattern of escape, and the exceptional density of HIV-1 envelope glycosylation generally, led us to postulate an evolving 'glycan shield' mechanism of neutralization escape whereby selected changes in glycan packing prevent Nab binding but not receptor binding. Direct support for this model was obtained by mutational substitution showing that Nab-selected alterations in glycosylation conferred escape from both autologous antibody and epitope-specific monoclonal antibodies. The evolving glycan shield thus represents a new mechanism contributing to HIV-1 persistence in the face of an evolving antibody repertoire. 相似文献
152.
The composition of mid-ocean-ridge basalt is known to correlate with attributes such as ridge topography and seismic velocity in the underlying mantle, and these correlations have been interpreted to reflect variations in the average extent and mean pressures of melting during mantle upwelling. In this respect, the eastern extremity of the southwest Indian ridge is of special interest, as its mean depth of 4.7 km (ref. 4), high upper-mantle seismic wave velocities and thin oceanic crust of 4-5 km (ref. 6) suggest the presence of unusually cold mantle beneath the region. Here we show that basaltic glasses dredged in this zone, when compared to other sections of the global mid-ocean-ridge system, have higher Na(8.0), Sr and Al2O3 compositions, very low CaO/Al2O3 ratios relative to TiO2 and depleted heavy rare-earth element distributions. This signature cannot simply be ascribed to low-degree melting of a typical mid-ocean-ridge source mantle, as different geochemical indicators of the extent of melting are mutually inconsistent. Instead, we propose that the mantle beneath approximately 1,000 km of the southwest Indian ridge axis has a complex history involving extensive earlier melting events and interaction with partial melts of a more fertile source. 相似文献
153.
The Carnivora are one of only four orders of terrestrial mammals living in Madagascar today. All four (carnivorans, primates, rodents and lipotyphlan insectivores) are placental mammals with limited means for dispersal, yet they occur on a large island that has been surrounded by a formidable oceanic barrier for at least 88 million years, predating the age of origin for any of these groups. Even so, as many as four colonizations of Madagascar have been proposed for the Carnivora alone. The mystery of the island's mammalian origins is confounded by its poor Tertiary fossil record, which leaves us with no direct means for estimating dates of initial diversification. Here we use a multi-gene phylogenetic analysis to show that Malagasy carnivorans are monophyletic and thus the product of a single colonization of Madagascar by an African ancestor. Furthermore, a bayesian analysis of divergence ages for Malagasy carnivorans and lemuriforms indicates that their respective colonizations were temporally separated by tens of millions of years. We therefore conclude that a single event, such as vicariance or common dispersal, cannot explain the presence of both groups in Madagascar. 相似文献
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In the brain, hippocampal pyramidal cells use temporal as well as rate coding to signal spatial aspects of the animal's environment or behaviour. The temporal code takes the form of a phase relationship to the concurrent cycle of the hippocampal electroencephalogram theta rhythm. These two codes could each represent a different variable. However, this requires the rate and phase to vary independently, in contrast to recent suggestions that they are tightly coupled, both reflecting the amplitude of the cell's input. Here we show that the time of firing and firing rate are dissociable, and can represent two independent variables: respectively the animal's location within the place field, and its speed of movement through the field. Independent encoding of location together with actions and stimuli occurring there may help to explain the dual roles of the hippocampus in spatial and episodic memory, or may indicate a more general role of the hippocampus in relational/declarative memory. 相似文献
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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
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Quigg A Finkel ZV Irwin AJ Rosenthal Y Ho TY Reinfelder JR Schofield O Morel FM Falkowski PG 《Nature》2003,425(6955):291-294
Phytoplankton is a nineteenth century ecological construct for a biologically diverse group of pelagic photoautotrophs that share common metabolic functions but not evolutionary histories. In contrast to terrestrial plants, a major schism occurred in the evolution of the eukaryotic phytoplankton that gave rise to two major plastid superfamilies. The green superfamily appropriated chlorophyll b, whereas the red superfamily uses chlorophyll c as an accessory photosynthetic pigment. Fossil evidence suggests that the green superfamily dominated Palaeozoic oceans. However, after the end-Permian extinction, members of the red superfamily rose to ecological prominence. The processes responsible for this shift are obscure. Here we present an analysis of major nutrients and trace elements in 15 species of marine phytoplankton from the two superfamilies. Our results indicate that there are systematic phylogenetic differences in the two plastid types where macronutrient (carbon:nitrogen:phosphorus) stoichiometries primarily reflect ancestral pre-symbiotic host cell phenotypes, but trace element composition reflects differences in the acquired plastids. The compositional differences between the two plastid superfamilies suggest that changes in ocean redox state strongly influenced the evolution and selection of eukaryotic phytoplankton since the Proterozoic era. 相似文献