The role of BST2/tetherin in feline retrovirus infection

Pathogenic retroviral infections of mammals have induced the evolution of cellular anti-viral restriction factors and have shaped their biological activities. This intrinsic immunity plays an important role in controlling viral replication and imposes a barrier to viral cross-species transmission. Well-studied examples of such host restriction factors are TRIM5α, an E3 ubiquitin ligase that binds incoming retroviral capsids in the cytoplasm via its C-terminal PRY/SPRY (B30.2) domain and targets them for proteasomal degradation, and APOBEC3 proteins, cytidine deaminases that induce hypermutation and impair viral reverse transcription. Tetherin (BST-2, CD317) is an interferon-inducible transmembrane protein that potently inhibits the release of nascent retrovirus particles in single-cycle replication assays. However, whether the primary biological activity of tetherin in vivo is that of a restriction factor remains uncertain as recent studies on human tetherin suggest that it is unable to prevent spreading infection of human immunodeficiency virus type 1 (HIV-1). The feline tetherin homologue resembles human tetherin in amino acid sequence, protein topology and anti-viral activity. Transiently expressed feline tetherin displays potent inhibition of feline immunodeficiency virus (FIV) and HIV-1 particle release. However, stable ectopic expression of feline tetherin in a range of feline cell lines has no inhibitory effect on the growth of either primary or cell culture-adapted strains of FIV. By comparing and contrasting the activities of the felid and primate tetherins against their respective immunodeficiency-causing lentiviruses we may gain insight into the contribution of tetherins to the control of lentiviral replication and the evolution of lentiviral virulence

Restriction of the felid lentiviruses by a synthetic feline TRIM5-CypA fusion

Gene therapy approaches to the treatment of HIV infection have targeted both viral gene expression and the cellular factors that are essential for virus replication. However, significant concerns have been raised regarding the potential toxic effects of such therapies, the emergence of resistant viral variants and unforeseen biological consequences such as enhanced susceptibility to unrelated pathogens. Novel restriction factors formed by the fusion of the tripartite motif protein (TRIM5) and cyclophilin A (CypA), or "TRIMCyps", offer an effective antiviral defence strategy with a very low potential for toxicity. In order to investigate the potential therapeutic utility of TRIMCyps in gene therapy for AIDS, a synthetic fusion protein between feline TRIM5 and feline CypA was generated and transduced into cells susceptible to infection with feline immunodeficiency virus (FIV). The synthetic feline TRIMCyp was highly efficient at preventing infection with both HIV and FIV and the cells resisted productive infection with FIV from either the domestic cat or the puma. Feline TRIMCyp and FIV infection of the cat offers a unique opportunity to evaluate TRIMCyp-based approaches to genetic therapy for HIV infection and the treatment of AIDS

Tree pruner: An efficient tool for selecting data from a biased genetic database

<p>Abstract</p> <p>Background</p> <p>Large databases of genetic data are often biased in their representation. Thus, selection of genetic data with desired properties, such as evolutionary representation or shared genotypes, is problematic. Selection on the basis of epidemiological variables may not achieve the desired properties. Available automated approaches to the selection of influenza genetic data make a tradeoff between speed and simplicity on the one hand and control over quality and contents of the dataset on the other hand. A poorly chosen dataset may be detrimental to subsequent analyses.</p> <p>Results</p> <p>We developed a tool, <it>Tree Pruner</it>, for obtaining a dataset with desired evolutionary properties from a large, biased genetic database. Tree Pruner provides the user with an interactive phylogenetic tree as a means of editing the initial dataset from which the tree was inferred. The tree visualization changes dynamically, using colors and shading, reflecting Tree Pruner actions. At the end of a Tree Pruner session, the editing actions are implemented in the dataset.</p> <p>Currently, Tree Pruner is implemented on the Influenza Research Database (IRD). The data management capabilities of the IRD allow the user to store a pruned dataset for additional pruning or for subsequent analysis. Tree Pruner can be easily adapted for use with other organisms.</p> <p>Conclusions</p> <p>Tree Pruner is an efficient, manual tool for selecting a high-quality dataset with desired evolutionary properties from a biased database of genetic sequences. It offers an important alternative to automated approaches to the same goal, by providing the user with a dynamic, visual guide to the ongoing selection process and ultimate control over the contents (and therefore quality) of the dataset.</p

Impact of road traffic noise annoyance on health-related quality of life: results from a population-based study

Purpose: To estimate the impact of traffic-related noise annoyance on health-related quality of life (HrQoL) in a population-based study and potential effect modification by gender. Methods: The study included 5,021 participants of the Swiss Cohort Study of Air Pollution and Lung Disease in Adults second survey. The association between traffic-related noise annoyance, measured on an 11-point scale, and HrQoL, based on SF-36 scores, was investigated by multivariate regression analysis. Effect sizes were calculated, and interactions by gender and chronic disease status examined. Results: Thirteen percentage of the study population reported high annoyance due to traffic. Women were more likely to report high noise annoyance (adjOR 1.23; 95%CI 1.01-1.48). Except for general health, all SF-36 scores showed a significant negative association with noise annoyance. The respective effect sizes ranged between 0.13 and 0.54. Significant effect modification by gender and chronic disease status was present in specific SF-36 domains. Conclusion: This paper presents first evidence of an inverse relationship of noise annoyance and HrQoL in a general population. Although the estimated effects are small to moderate for individuals, they may add up to a relevant public health impac

Estimating abortion incidence using the network scale-up method

Background: A major challenge in abortion research is accurately measuring the incidence of induced abortion, particularly in restrictive settings. This study tests the network scale-up method (NSUM) to measure abortion incidence, which uses respondent social network data to estimates the size of hidden populations. Methods: Using NSUM modules added to the Ethiopia and Uganda 2018 Performance Monitoring for Action (PMA) community-based surveys, we compute NSUM abortion incidence ratios, and adjust these ratios to account for transmission bias. We conduct internal validity checks to assess the NSUM performance. Results: The unadjusted NSUM abortion ratios were likely underestimates (Uganda: 15.3 per 100 births, Ethiopia: 3.6 per 100 births). However, the transmission bias-adjusted NSUM abortion ratios grossly overestimated abortion (Uganda: 151.4 per 100 births, Ethiopia: 73.9 per 100 births), which was likely due to selection bias, question wording, and the use of lifetime abortions to measure transmission bias. Internal validity checks revealed problems with the NSUM application in Ethiopia. Unadjusted NSUM estimates of intrauterine device/implant use performed well compared to established external estimates, but adjusting for transmission bias again resulted in overestimation. Conclusions: The NSUM resulted in overestimates of abortion incidence in Ethiopia and Uganda. We discuss several modifications that may improve future applications of the NSUM for measuring abortion. Contribution: This is the first test of the NSUM to estimate national abortion incidence. Our findings highlight the critical need to assess the validity of abortion estimates, a key feature of the NSUM that is lacking in most other indirect abortion measurement methods

Seismic imaging of the 1999 Izmit (Turkey) Rupture inferred from the near‐fault recordings

International audienceWe use near-fault accelerograms to infer the space-time history of rupture on the fault during the Izmit earthquake. The records show that the ground displacement and velocity near the fault were surprisingly simple. Rupture propagated toward the west at a velocity of about 3 km/s, and toward the east at a remarkably high average velocity of 4.7 km/s over a distance of about 45 km before decelerating to about 3.1 km/s on the eastern segment. Slip on the fault is particularly large down to a depth of 20 km on the central portion of the fault where it reaches about 7 m. Slip is large also below 10 km on the eastern fault segment, and this may have contributed to the loading of shear stress on the Diizce fault. On the western fault segment, large slip seems confined to shallow depths. is located very close to ARC, and the ground velocities there display waveforms and amplitudes similar to those at ARC. The digital records at ARC are, however, of much better quality than the analog records at GBZ, and, for this reason, we shall use ARC as our modeling station. The other station that we did not use is YPT because records there are more complicated and have a longer duration than records at ARC and SKR, located further from the epicenter. This complexity suggests that at this station the records are more affected by the shallow crustal structure below the site or between the station and the fault

Nurses Alumni Association Bulletin, Fall 1994

1994-1995 Meeting Dates Calendar 1995 Annual Luncheon - Meeting Notice Officers and Committee Chairs Bulletin Publication Committee 1994-1995 Meeting Dates Calendar The President\u27s Message Treasurer\u27s Report News About Our Graduates Fiftieth Anniversary Resume of Minutes of Alumni Association Meetings Department of Nursing 1993-1994 Alumni Office News Jefferson 2000 Fund The Women\u27s Center for Health Promotion Discount Parking for Alumni Cadet Nurse Corps Medical Anecdotes of Faith Ukranian-American Teacher Exchange Happy Birthday Committee Reports In Memoriam, Names of Deceased Graduates Luncheon Photos Class News Jefferson Alumni Identification Card Relief Fund Application Scholarship Application Membership Application Pins, Transcripts, Class Address Lists, Change of address Forms Campus Ma

Community Engaged Cumulative Risk Assessment of Exposure to Inorganic Well Water Contaminants, Crow Reservation, Montana

An estimated 11 million people in the US have home wells with unsafe levels of hazardous metals and nitrate. The national scope of the health risk from consuming this water has not been assessed as home wells are largely unregulated and data on well water treatment and consumption are lacking. Here, we assessed health risks from consumption of contaminated well water on the Crow Reservation by conducting a community-engaged, cumulative risk assessment. Well water testing, surveys and interviews were used to collect data on contaminant concentrations, water treatment methods, well water consumption, and well and septic system protection and maintenance practices. Additive Hazard Index calculations show that the water in more than 39% of wells is unsafe due to uranium, manganese, nitrate, zinc and/or arsenic. Most families’ financial resources are limited, and 95% of participants do not employ water treatment technologies. Despite widespread high total dissolved solids, poor taste and odor, 80% of families consume their well water. Lack of environmental health literacy about well water safety, pre-existing health conditions and limited environmental enforcement also contribute to vulnerability. Ensuring access to safe drinking water and providing accompanying education are urgent public health priorities for Crow and other rural US families with low environmental health literacy and limited financial resources