Packaging signals in single-stranded RNA viruses: nature’s alternative to a purely electrostatic assembly mechanism

The formation of a protective protein container is an essential step in the life-cycle of most viruses. In the case of single-stranded (ss)RNA viruses, this step occurs in parallel with genome packaging in a co-assembly process. Previously, it had been thought that this process can be explained entirely by electrostatics. Inspired by recent single-molecule fluorescence experiments that recapitulate the RNA packaging specificity seen in vivo for two model viruses, we present an alternative theory, which recognizes the important cooperative roles played by RNA–coat protein interactions, at sites we have termed packaging signals. The hypothesis is that multiple copies of packaging signals, repeated according to capsid symmetry, aid formation of the required capsid protein conformers at defined positions, resulting in significantly enhanced assembly efficiency. The precise mechanistic roles of packaging signal interactions may vary between viruses, as we have demonstrated for MS2 and STNV. We quantify the impact of packaging signals on capsid assembly efficiency using a dodecahedral model system, showing that heterogeneous affinity distributions of packaging signals for capsid protein out-compete those of homogeneous affinities. These insights pave the way to a new anti-viral therapy, reducing capsid assembly efficiency by targeting of the vital roles of the packaging signals, and opens up new avenues for the efficient construction of protein nanocontainers in bionanotechnology

GPU Accelerated Smith-Waterman

We present a novel hardware implementation of the double affine Smith-Waterman (DASW) algorithm, which uses dynamic programming to compare and align genomic sequences such as DNA and proteins. We implement DASW on a commodity graphics card, taking advantage of the general purpose programmability of the graphics processing unit to leverage its cheap parallel processing power. The results demonstrate that our system's performance is competitive with current optimized software packages

An assessment of a three-beam Doppler lidar wind profiling method for use in urban areas

Currently there are few observations of the urban wind field at heights other than rooftop level. Remote sensing instruments such as Doppler lidars provide wind speed data at many heights, which would be useful in determining wind loadings of tall buildings, and predicting local air quality. Studies comparing remote sensing with traditional anemometers carried out in flat, homogeneous terrain often use scan patterns which take several minutes. In an urban context the flow changes quickly in space and time, so faster scans are required to ensure little change in the flow over the scan period. We compare 3993 h of wind speed data collected using a three-beam Doppler lidar wind profiling method with data from a sonic anemometer (190 m). Both instruments are located in central London, UK; a highly built-up area. Based on wind profile measurements every 2 min, the uncertainty in the hourly mean wind speed due to the sampling frequency is 0.05–0.11 m s−1. The lidar tended to overestimate the wind speed by ≈0.5 m s−1 for wind speeds below 20 m s−1. Accuracy may be improved by increasing the scanning frequency of the lidar. This method is considered suitable for use in urban areas

Global typologies of coastal wetland status to inform conservation and management

Global-scale conservation initiatives and policy instruments rely on ecosystem indicators to track progress towards targets and objectives. A deeper understanding of indicator interrelationships would benefit these efforts and help characterize ecosystem status. We study interrelationships among 34 indicators for mangroves, saltmarsh, and seagrass ecosystems, and develop data-driven, spatially explicit typologies of coastal wetland status at a global scale. After accounting for environmental covariates and gap-filling missing data, we obtained two levels of clustering at 5 and 18 typologies, providing outputs at different scales for different end users. We generated 2,845 cells (1° (lat) × 1° (long)) globally, of which 29.7% were characterized by high land- and marine-based impacts and a high proportion of threatened species, 13.5% by high climate-based impacts, and 9.6% were refuges with lower impacts, high fish density and a low proportion of threatened species. We identify instances where specific actions could have positive outcomes for coastal wetlands across regions facing similar issues. For example, land- and marine-based threats to coastal wetlands were associated with ecological structure and function indicators, suggesting that reducing these threats may reduce habitat degradation and threats to species persistence. However, several interdimensional relationships might be affected by temporal or spatial mismatches in data. Weak relationships mean that global biodiversity maps that categorize areas by single indicators (such as threats or trends in habitat size) may not be representative of changes in other indicators (e.g., ecosystem function). By simplifying the complex global mosaic of coastal wetland status and identifying regions with similar issues that could benefit from knowledge exchange across national boundaries, we help set the scene for globally and regionally coordinated conservation

Internalized HIV Stigma Predicts Suboptimal Retention in Care among People Living with HIV in the United States

HIV-related stigma is a known barrier to retention in care. However, no large-scale, multi-site studies have prospectively evaluated the effect of internalized stigma on retention in care. The Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort study integrates medical record and survey data from people living with HIV (PLWH) seen in HIV primary care clinics across the United States, and assesses internalized stigma yearly using a validated 4-item Likert scale. We used multivariable logistic regression models to evaluate associations between mean internalized stigma and two prospective retention in care outcomes: keeping the next primary care appointment and keeping all scheduled primary care appointments in the 12 months following stigma assessment. From February 2016 to November 2017, 5968 PLWH completed the stigma assessment and had adequate follow-up time. Mean stigma was 1.9 (standard deviation 1.08). Increased mean stigma scores were associated with decreased odds of attending the next primary care appointment [adjusted odds ratio (aOR) = 0.93, 95% confidence interval (CI) 0.88-0.99, p = 0.02], and all primary care appointments in the subsequent 12 months (aOR = 0.94, 95% CI 0.89-0.99, p = 0.02). In both models, younger age and Black race were also independently associated with suboptimal appointment attendance. There was no support for interactions between internalized stigma and covariates. Internalized HIV stigma had an independent negative effect on the odds of subsequent appointment attendance. This study highlights the importance of identifying even low levels of internalized stigma. Interventions to address internalized HIV stigma are critical to supporting retention in care and improving clinical outcomes

Professional closure by proxy: the impact of changing educational requirements on class mobility for a cohort of Big 8 partners

Closure events impacting on class mobility may include mechanisms initiated by bodies other than the professional body. The research examines if the introduction of full-time study requirements at universities for aspiring accountants effectively introduced a closure mechanism in the accounting profession. Data was derived from an Oral History study of partners in large firms. The younger partners (born after the Second World War) completed full-time degree study at university, but did not provide evidence of class mobility into the profession. The older cohort, born between 1928 and 1946, completed part-time studies only, few completed a degree, and, in contrast to the younger cohort, shows a perceptible upward movement from lower socio-economic classes into the professional class. This suggests that changing the preferred educational routes for new accountants entering the large chartered accounting (CA) firms compromised the "stepping stone" function of accounting as a portal into the professional class

Brane inflation revisited after WMAP five-year results

In this paper, we revisit brane inflation models with the WMAP five-year results. The WMAP five-year data favor a red-tilted power spectrum of primordial fluctuations at the level of two standard deviations, which is the same as the WMAP three-year result qualitatively, but quantitatively the spectral index is slightly greater than the three-year value. This result can bring impacts on brane inflation models. According to the WMAP five-year data, we find that the KKLMMT model can survive at the level of one standard deviation, and the fine-tuning of the parameter $\beta$ can be alleviated to a certain extent at the level of two standard deviations.Comment: 23 pages, 11 figure