505 research outputs found

    A library of infectious hepatitis C viruses with engineered mutations in the E2 gene reveals growth-adaptive mutations that modulate interactions with scavenger receptor class B type I

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    While natural hepatitis C virus (HCV) infection results in highly diverse quasispecies of related viruses over time, mutations accumulate more slowly in tissue culture, in part because of the inefficiency of replication in cells. To create a highly diverse population of HCV particles in cell culture and identify novel growth-enhancing mutations, we engineered a library of infectious HCV with all codons represented at most positions in the ectodomain of the E2 gene. We identified many putative growth-adaptive mutations and selected nine highly represented E2 mutants for further study: Q412R, T416R, S449P, T563V, A579R, L619T, V626S, K632T, and L644I. We evaluated these mutants for changes in particle-to-infectious-unit ratio, sensitivity to neutralizing antibody or CD81 large extracellular loop (CD81-LEL) inhibition, entry factor usage, and buoyant density profiles. Q412R, T416R, S449P, T563V, and L619T were neutralized more efficiently by anti-E2 antibodies and T416R, T563V, and L619T by CD81-LEL. Remarkably, all nine variants showed reduced dependence on scavenger receptor class B type I (SR-BI) for infection. This shift from SR-BI usage did not correlate with a change in the buoyant density profiles of the variants, suggesting an altered E2-SR-BI interaction rather than changes in the virus-associated lipoprotein-E2 interaction. Our results demonstrate that residues influencing SR-BI usage are distributed across E2 and support the development of large-scale mutagenesis studies to identify viral variants with unique functional properties. IMPORTANCE Characterizing variant viruses can reveal new information about the life cycle of HCV and the roles played by different viral genes. However, it is difficult to recapitulate high levels of diversity in the laboratory because of limitations in the HCV culture system. To overcome this limitation, we engineered a library of mutations into the E2 gene in the context of an infectious clone of the virus. We used this library of viruses to identify nine mutations that enhance the growth rate of HCV. These growth-enhancing mutations reduced the dependence on a key entry receptor, SR-BI. By generating a highly diverse library of infectious HCV, we mapped regions of the E2 protein that influence a key virus-host interaction and provide proof of principle for the generation of large-scale mutant libraries for the study of pathogens with great sequence variability

    Autobed: A Web-Controlled Robotic Bed

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    We (the Healthcare Robotics Lab at Georgia Tech) have developed an additional module for an Invacare fully electric hospital bed (Model 5410IVC) so that the bed can be controlled from a web-based interface. This module can be easily plugged between the hand control and the Invacare bed, without having to modify any existing hardware on the bed. We call a bed so modified an 'Autobed.' With this feature, users who are unable to operate the standard bed controls, but can access a web browser, are able to position the bed by themselves without having to rely on a caregiver (for example, patients with quadriplegia). This page describes how to make the Autobed module using relatively inexpensive, commercially available hardware. This document is a representation of the content provided at http://hsi.gatech.edu/hrl/project_autobed_v2.shtml as of February 15th, 2016, and is intended to create a lasting, citable, and archival copy of this material, which details the design and instructions for building the 'Autobed' device

    Improving averted loss estimates for better biodiversity outcomes from offset exchanges

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    Biodiversity offsetting aims to achieve at least ‘no net loss’ of biodiversity by fully compensating for residual development-induced biodiversity losses after the mitigation hierarchy (avoid, minimise, remediate) has been applied. Actions used to generate offsets can include securing protection, maintaining condition, or enhancing condition of targeted biodiversity at an offset site. Protection and maintenance actions aim to prevent future loss of biodiversity, so such offsets are referred to as ‘averted loss’ offsets. However, the benefits of such approaches can be highly uncertain and opaque, because assumptions about the change in likelihood of loss due to the offset are often implicit. As a result, the gain generated by averting losses can be intentionally or inadvertently overestimated, leading to offset outcomes that are insufficient for achieving no net loss of biodiversity. We present a method and decision tree to guide consistent and credible estimation of the likelihood of loss of a proposed offset site with and without protection, for use when calculating the amount of benefit associated with the ‘protection’ component of averted loss offsets. In circumstances such as when a jurisdictional offset policy applies to most impacts, plausible estimates of averted loss can be very low. Averting further loss of biodiversity is desirable, and averted loss offsets can be a valid approach for generating tangible gains. However, overestimation of averted loss benefits poses a major risk to biodiversity

    Understanding the social inclusion needs of people living in mental health supported accommodation

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    Objectives: To identify the social inclusion needs that were (i) most commonly identified and (ii) most and least commonly prioritised as support planning goals for mental health service users living in supported accommodation, using the online Social Inclusion Questionnaire User Experience (SInQUE). We qualitatively examined mental health supported accommodation staff and servicer users’ views on barriers to offering support with two less commonly prioritised areas: help finding a partner and feeling less lonely. // Methods: Anonymous SInQUE data were collected during a completed study in which we developed and tested the online SInQUE. Four focus groups were conducted with mental health supported accommodation staff (N = 2) and service users (N = 2). // Results: The most common social inclusion needs identified by service users (N = 31) were leisure activities, finding transport options, and feeling less lonely. Of the needs identified, those that service users and staff least frequently prioritised as support planning goals were having company at mealtimes, getting one’s own furniture, feeling less lonely, help with finances, and help finding a partner. In the focus groups, staff and service users identified barriers to helping with loneliness and finding a partner which related to staff and service users themselves, supported accommodation services, and wider societal factors

    The Sudden Death of the Nearest Quasar

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    Galaxy formation is significantly modulated by energy output from supermassive black holes at the centers of galaxies which grow in highly efficient luminous quasar phases. The timescale on which black holes transition into and out of such phases is, however, unknown. We present the first measurement of the shutdown timescale for an individual quasar using X-ray observations of the nearby galaxy IC 2497, which hosted a luminous quasar no more than 70,000 years ago that is still seen as a light echo in `Hanny's Voorwerp', but whose present-day radiative output is lower by at least 2 and more likely by over 4 orders of magnitude. This extremely rapid shutdown provides new insights into the physics of accretion in supermassive black holes, and may signal a transition of the accretion disk to a radiatively inefficient state.Comment: 4 pages, 2 figures. Astrophysical Journal Letters, in pres

    Prioritizing conservation investments for mammal species globally

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    We need to set priorities for conservation because we cannot do everything, everywhere, at the same time. We determined priority areas for investment in threat abatement actions, in both a cost-effective and spatially and temporally explicit way, for the threatened mammals of the world. Our analysis presents the first fine-resolution prioritization analysis for mammals at a global scale that accounts for the risk of habitat loss, the actions required to abate this risk, the costs of these actions and the likelihood of investment success. We evaluated the likelihood of success of investments using information on the past frequency and duration of legislative effectiveness at a country scale. The establishment of new protected areas was the action receiving the greatest investment, while restoration was never chosen. The resolution of the analysis and the incorporation of likelihood of success made little difference to this result, but affected the spatial location of these investments
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