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1.
A single positively selected West Nile viral mutation confers increased virogenesis in American crows 总被引:1,自引:0,他引:1
Brault AC Huang CY Langevin SA Kinney RM Bowen RA Ramey WN Panella NA Holmes EC Powers AM Miller BR 《Nature genetics》2007,39(9):1162-1166
West Nile virus (WNV), first recognized in North America in 1999, has been responsible for the largest arboviral epiornitic and epidemic of human encephalitis in recorded history. Despite the well-described epidemiological patterns of WNV in North America, the basis for the emergence of WNV-associated avian pathology, particularly in the American crow (AMCR) sentinel species, and the large scale of the North American epidemic and epiornitic is uncertain. We report here that the introduction of a T249P amino acid substitution in the NS3 helicase (found in North American WNV) in a low-virulence strain was sufficient to generate a phenotype highly virulent to AMCRs. Furthermore, comparative sequence analyses of full-length WNV genomes demonstrated that the same site (NS3-249) was subject to adaptive evolution. These phenotypic and evolutionary results provide compelling evidence for the positive selection of a mutation encoding increased viremia potential and virulence in the AMCR sentinel bird species. 相似文献
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Neurotransmission from mossy fibre terminals onto cerebellar granule cells is almost certainly mediated by L-glutamate. By taking advantage of the small soma size, limited number of processes and short dendrite length of granule cells, we have obtained high-resolution recordings of spontaneous miniature excitatory postsynaptic currents (m.e.p.s.cs) and evoked currents in thin cerebellar slices. Miniature currents have a similar time-course and pharmacology to evoked currents and consist of an exceptionally fast non-NMDA (N-methyl-D-aspartate) component (measured rise-time, 200 microseconds; estimated pre-filtered rise-time less than 100 microseconds; decay time constant, tau = 1.0 ms), followed by 50 pS NMDA channel openings that are directly resolvable. We could find no evidence for the recent proposal that miniature currents in granule cells are mediated solely by NMDA channels with a novel time course. The non-NMDA receptor component of m.e.p.s.cs has a skewed amplitude distribution, which suggests potential complications for quantal analysis. The difference in time course between the m.e.p.s.cs reported here and other synaptic currents in the brain could reflect differences in synaptic function or electrotonic filtering; the relative contribution of these possibilities has yet to be established. 相似文献
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R. S. Verma S. Thomas M. Coleman R. T. Silver H. Dosik 《Cellular and molecular life sciences : CMLS》1986,42(4):440-441
Summary A random distribution of the Y-chromosome at somatic metaphase was found in 50 patients with Ph' positive chronic myelogenous leukemia (CML). Thus, it is concluded that the positive of the Y-chromosome at somatic metaphase does not appear to influence the loss from bone marrow cells. 相似文献
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The focus with which the paper is concerned is the process or task of intervention and, more specifically, the exploration of three (overlapping and interacting) questions pertinent to those who would intervene: What is to be done? How shall we decide what to do? What can guide our actions? In terms of what we will describe as pragmatic pluralism (our response to these questions), we intend this to be read in several different ways and on several different levels. Illustrating the discussion with examples from a number of different case studies, we will talk about pluralism in each of the following features: in the use of specific methods/techniques in the role(s) of the interventionists in the modes of representation employed in the use of different rationalities in the ‘nature’ of the client 相似文献
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Zhou T Xu L Dey B Hessell AJ Van Ryk D Xiang SH Yang X Zhang MY Zwick MB Arthos J Burton DR Dimitrov DS Sodroski J Wyatt R Nabel GJ Kwong PD 《Nature》2007,445(7129):732-737
The remarkable diversity, glycosylation and conformational flexibility of the human immunodeficiency virus type 1 (HIV-1) envelope (Env), including substantial rearrangement of the gp120 glycoprotein upon binding the CD4 receptor, allow it to evade antibody-mediated neutralization. Despite this complexity, the HIV-1 Env must retain conserved determinants that mediate CD4 binding. To evaluate how these determinants might provide opportunities for antibody recognition, we created variants of gp120 stabilized in the CD4-bound state, assessed binding of CD4 and of receptor-binding-site antibodies, and determined the structure at 2.3 A resolution of the broadly neutralizing antibody b12 in complex with gp120. b12 binds to a conformationally invariant surface that overlaps a distinct subset of the CD4-binding site. This surface is involved in the metastable attachment of CD4, before the gp120 rearrangement required for stable engagement. A site of vulnerability, related to a functional requirement for efficient association with CD4, can therefore be targeted by antibody to neutralize HIV-1. 相似文献