6,650 research outputs found
Natural variation of the nef gene in human immunodeficiency virus type 2 infections in Portugal
Human immunodeficiency virus type 2 (HIV-2) infections cause severe immunodeficiency in humans, although HIV-2 is associated frequently with reduced virulence and pathogenicity compared to HIV-1. Genetic determinants that play a role in HIV pathogenesis are relatively poorly understood but nef has been implicated in inducing a more pathogenic phenotype in vivo. However, relatively little is known about the role of nef in HIV-2 pathogenesis. To address this, the genetic composition of 44 nef alleles from 37 HIV-2-infected individuals in Portugal, encompassing a wide spectrum of disease associations, CD4 counts and virus load, has been assessed. All nef alleles were subtype A, with no evidence of gross deletions, truncations or disruptions in the nef-encoding sequence; all were full-length and intact. HIV-2 long terminal repeat sequences were conserved and also indicated subtype A infections. Detailed analysis of motifs that mediate nef function in HIV-1 and simian immunodeficiency virus, such as CD4 downregulation and putative SH2/SH3 interactions, revealed significant natural variation. In particular, the central P(104)xxPLR motif exhibited wide interpatient variation, ranging from an HIV-1-like tetra-proline structure (PxxP)(3) to a disrupted minimal core motif (P(104)xxQLR). The P(107)-->Q substitution was associated with an asymptomatic phenotype (Fisher's exact test, P=0.026) and low virus loads. These data indicate that discrete differences in the nef gene sequence rather than gross structural changes are more likely to play a role in HIV-2 pathogenesis mediated via specific functional interactions
Recommended from our members
An in-plane photoelectric effect in two-dimensional electron systems for terahertz detection
Many mid- and far-infrared semiconductor photodetectors rely on a photonic response, when the photon energy is large enough to excite and extract electrons due to optical transitions. Toward the terahertz range with photon energies of a few milliâelectron volts, classical mechanisms are used instead. This is the case in two-dimensional electron systems, where terahertz detection is dominated by plasmonic mixing and by scattering-based thermal phenomena. Here, we report on the observation of a quantum, collision-free phenomenon that yields a giant photoresponse at terahertz frequencies (1.9 THz), more than 10-fold as large as expected from plasmonic mixing. We artificially create an electrically tunable potential step within a degenerate two-dimensional electron gas. When exposed to terahertz radiation, electrons absorb photons and generate a large photocurrent under zero source-drain bias. The observed phenomenon, which we call the âin-plane photoelectric effect,â provides an opportunity for efficient direct detection across the entire terahertz range.George and Lilian Schiff Studentship, Schiff Foundation, University of Cambridge
Honorary Vice-Chancellorâs Award, Cambridge Trust, University of Cambridg
Using seasonal forecasts to inform the management of water resources during drought
Water is considered to be one of the main mechanisms through which people will experience climate change, with the number of people estimated to become exposed to water scarcity projected to increase sharply in the future. Water resource managers in the UK have access to a range of meteorological and hydrological indicators of drought. However these data are limited in their utility to directly forecast how systems should be managed to reduce impacts on water users. At present there is no generically applicable method to provide such an outlook.
We are working with practitioners and regulators in the UK water industry to demonstrate the use of seasonal forecasts to support decision-making during drought. The work is funded by Copernicus through the European Centre for Medium-Range Weather Forecasts (ECMWF) with the aim of showing how Copernicus Climate Change Service (C3S) data can be used in sectoral contexts. C3S data are combined with both operational practices and the latest UK water resources planning developments to provide metrics of value tailored to the needs of water resource managers. National and industry stakeholders have been fully engaged from the outset, co-creating a tool to evaluate, visualise, and communicate the potential impact of emerging droughts in a meaningful way.
The tool reads water supply system information presented by water companies including drought response surfaces, operational decisions, and demand. The water supply system is simulated using seasonal forecasts, and an assessment of drought likelihood and vulnerability is provided along with an estimate of the associated uncertainty. Impacts are presented in terms of consequences for stakeholders and contextualised in terms of system vulnerabilities and the historic record. This tool supports operational decision-making, in particular when deliberating the timing of supply and demand-side interventions as a drought develops, and communicating such risks to stakeholders
Review of Large Carnivore Conservation: Integrating Science and Policy in the North American West
The management and conservation of large carnivores is of worldwide concern and is as much about human values, interactions, and governance as carnivore biology. Susan Clark and Murray Rutherford continue their work on coexisting with large carnivores ( Clark et al. 2005 ) with a new edited volume Large Carnivore Conservation: Integrating Science and Policy in the North American West . Large Carnivore Conservation that expands on the same themes as their previous work with case studies from Arizona to the Yukon. While focusing on the North American West, Clark and Rutherford hope to provide a holistic approach to carnivore management in general
The enrichment of an alkaliphilic biofilm consortia capable of the anaerobic degradation of isosaccharinic acid from cellulosic materials incubated within an anthropogenic, hyperalkaline environment.
Anthropogenic hyper-alkaline sites provide an environment that is analogous to proposed cementitious geological disposal facilities (GDF) for radioactive waste. Under anoxic, alkaline conditions cellulosic wastes will hydrolyse to a range of cellulose degradation products (CDP) dominated by isosaccharinic acids (ISA). In order to investigate the potential for microbial activity in a cementitious GDF, cellulose samples were incubated in the alkaline (âŒpH 12), anaerobic zone of a lime kiln waste site. Following retrieval, these samples had undergone partial alkaline hydrolysis and were colonised by a Clostridia dominated biofilm community, where hydrogenotrophic, alkaliphilic methanogens were also present. When these samples were used to establish an alkaline CDP fed microcosm, the community shifted away from Clostridia, methanogens became undetectable and a flocculate community dominated by Alishewanella sp. established. These flocs were composed of bacteria embedded in polysaccharides and protein stabilised by extracellular DNA. This community was able to degrade all forms of ISA with >60% of the carbon flow being channelled into extracellular polymeric substance (EPS) production. This study demonstrated that alkaliphilic microbial communities can degrade the CDP associated with some radioactive waste disposal concepts at pH 11. These communities divert significant amounts of degradable carbon to EPS formation, suggesting that EPS has a central role in the protection of these communities from hyper-alkaline conditions
- âŠ