Translational Recoding Induced by G-Rich mRNA Sequences That Form Unusual Structures

AbstractWe investigated a herpesvirus mutant that contains a single base insertion in its thymidine kinase (tk) gene yet expresses low levels of TK via a net +1 translational recoding event. Within this mutant gene, we defined a G-rich signal that is sufficient to induce recoding. Unlike other translational recoding events, downstream RNA structures or termination codons did not stimulate recoding, and paused ribosomes were not detected. Mutational analysis indicated that specific tRNAs or codon–anticodon slippage were unlikely to account for recoding. Rather, recoding efficiency correlated with the G-richness of the signal and its ability to form unusual structures. These findings identify a mechanism of translational recoding with unique features and potential implications for clinical drug resistance and other biological systems

The GirlStars Program: Challenges to Recruitment and Retention in a Physical Activity and Health Education Program for Adolescent Girls Living in Public Housing

BACKGROUND. Although physical inactivity is a concern for all adolescents, physical activity levels are especially low among minority adolescents and minimal among girls from low-income families. After-school programs can reduce high-risk behaviors and strengthen schools, families, and communities. CONTEXT. We conducted an operational research project that provided free access to a program of regular, organized physical activity combined with health education sessions for adolescent girls in 2 public housing developments in Boston, Massachusetts. METHODS. From July 2002 through October 2005, at each of 2 public housing sites, the GirlStars program participants met each week for two 2-hour sessions, 1 dedicated to physical activity and 1 dedicated to health education. Sessions were led by the project coordinator and a resident assistant at each development. OUTCOME. Participants in the GirlStars program increased their health knowledge, self-confidence, and decision-making skills, but rates of participation were low. Factors that affected participation included safety concerns, lack of community support for the program, interpersonal conflicts, attrition in staff, and conflicts with other activities. INTERPRETATION. Programs in public housing developments that address these barriers to recruitment and retention may be more successful and reach more girls

An Open Source Cyberinfrastructure for Collecting, Processing, Storing and Accessing High Temporal Resolution Residential Water Use Data

Collecting and managing high temporal resolution residential water use data is challenging due to cost and technical requirements associated with the volume and velocity of data collected. We developed an open-source, modular, generalized architecture called Cyberinfrastructure for Intelligent Water Supply (CIWS) to automate the process from data collection to analysis and presentation of high temporal residential water use data. A prototype implementation was built using existing open-source technologies, including smart meters, databases, and services. Two case studies were selected to test functionalities of CIWS, including push and pull data models within single family and multi-unit residential contexts, respectively. CIWS was tested for scalability and performance within our design constraints and proved to be effective within both case studies. All CIWS elements and the case study data described are freely available for re-use

Evaluation of exposure-specific risks from two independent samples: A simulation study

<p>Abstract</p> <p>Background</p> <p>Previous studies have proposed a simple product-based estimator for calculating exposure-specific risks (ESR), but the methodology has not been rigorously evaluated. The goal of our study was to evaluate the existing methodology for calculating the ESR, propose an improved point estimator, and propose variance estimates that will allow the calculation of confidence intervals (CIs).</p> <p>Methods</p> <p>We conducted a simulation study to test the performance of two estimators and their associated confidence intervals: 1) current (simple product-based estimator) and 2) proposed revision (revised product-based estimator). The first method for ESR estimation was based on multiplying a relative risk (RR) of disease given a certain exposure by an overall risk of disease. The second method, which is proposed in this paper, was based on estimates of the risk of disease in the unexposed. We then multiply the updated risk by the RR to get the revised product-based estimator. A log-based variance was calculated for both estimators. Also, a binomial-based variance was calculated for the revised product-based estimator. 95% CIs were calculated based on these variance estimates. Accuracy of point estimators was evaluated by comparing observed relative bias (percent deviation from the true estimate). Interval estimators were evaluated by coverage probabilities and expected length of the 95% CI, given coverage. We evaluated these estimators across a wide range of exposure probabilities, disease probabilities, relative risks, and sample sizes.</p> <p>Results</p> <p>We observed more bias and lower coverage probability when using the existing methodology. The revised product-based point estimator exhibited little observed relative bias (max: 4.0%) compared to the simple product-based estimator (max: 93.9%). Because the simple product-based estimator was biased, 95% CIs around this estimate exhibited small coverage probabilities. The 95% CI around the revised product-based estimator from the log-based variance provided better coverage in most situations.</p> <p>Conclusion</p> <p>The currently accepted simple product-based method was only a reasonable approach when the exposure probability is small (< 0.05) and the RR is ≤ 3.0. The revised product-based estimator provides much improved accuracy.</p

Serologic response to culture filtrate antigens of Mycobacterium ulcerans during Buruli ulcer disease.

Buruli ulcer (BU) is an emerging necrotic skin disease caused by Mycobacterium ulcerans. To assess the potential for a serodiagnostic test, we measured the humoral immune response of BU patients to M. ulcerans antigens and compared this response with delayed-type hypersensitivity responses to both Burulin and PPD. The delayed-type hypersensitivity response generally supported the diagnosis of BU, with overall reactivity to Burulin in 28 (71.8%) of 39 patients tested, compared with 3 (14%) of 21 healthy controls. However, this positive skin test response was observed primarily in patients with healed or active disease, and rarely in patients with early disease (p=0.009). When tested for a serologic response to M. ulcerans culture filtrate, 43 (70.5%) of 61 BU patients had antibodies to these antigens, compared with 10 (37.0%) of 27 controls and 4 (30. 8%) of 13 tuberculosis patients. There was no correlation between disease stage and the onset of this serum antibody response. Our findings suggest that serologic testing may be useful in the diagnosis and surveillance of BU

Testing the performance of environmental DNA metabarcoding for surveying highly diverse tropical fish communities: A case study from Lake Tanganyika

Background and Aims Environmental DNA (eDNA) metabarcoding provides a highly sensitive method of surveying freshwater fish communities, although studies to date have largely been restricted to temperate ecosystems. Due to limited reference sequence availability and challenges identifying closely related and rare species in diverse tropical ecosystems, the effectiveness of metabarcoding methods for surveying tropical fish communities from eDNA samples remains uncertain. To address this, we applied an eDNA metabarcoding approach to survey Lake Tanganyika's (LT) species‐rich littoral fish communities. Materials and Methods As this system contains many closely related species, particularly cichlid fishes, we used four primer sets including a cichlid‐specific primer set (Cichlid_CR). A reference database was built for the 12s, 16s, and control region for 358 fish species including over 93% of known cichlids. Results and Discussion In silico and in situ results demonstrated wide variability in the taxonomic resolution of assignments by each primer with the cichlid‐specific marker (Cichlid_CR) enabling greater species‐level assignments for this highly diverse family. A greater number of non‐cichlid teleost species were detected at sites compared to the visual survey data. For cichlid species however, sequencing depth substantially influenced species richness estimates obtained from eDNA samples, with increased depths producing estimates comparable to that obtained from the visual survey data. Conclusions Our study highlights the importance of sequencing depth and local reference databases when undertaking metabarcoding studies within diverse ecosystems, as well as demonstrating the potential of eDNA metabarcoding for surveying diverse tropical fish communities, even those containing closely related species within evolutionary radiations

Recent advances in drug discovery for diabetic kidney disease

Introduction: Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD), and 40% of patients with diabetes develop DKD. Although some pathophysiological mechanisms and drug targets of DKD have been described, the effectiveness or clinical usefulness of such treatment has not been well validated. Therefore, searching for new targets and potential therapeutic candidates has become an emerging research area. Areas covered: The pathophysiological mechanisms, new drug targets and potential therapeutic compounds for DKD are addressed in this review. Expert opinion: Although preclinical and clinical evidence has shown some positive results for controlling DKD progression, treatment regimens have not been well developed to reduce the mortality in patients with DKD globally. Therefore, the discovery of new therapeutic targets and effective target-based drugs to achieve better and safe treatment are urgently required. Preclinical screening and clinical trials for such drugs are needed

Whole-Genome Sequence of Staphylococcus epidermidis Tu3298

Staphylococcus epidermidis Tü3298 is a frequently used laboratory strain, known for its production of epidermin and absence of the icaABCD operon. We report the whole-genome sequence of this strain, a 2.5-kb genome containing 2,332 genes

Using vlogging to facilitate medical student reflection

Reflection is a critical skill for medical professionals, however medical students often find it difficult to grasp and engage with. During a special choice module on yoga and mindfulness, students practised mindfulness at home and posted their reflections on the activities in text and vlogs in a closed WhatsApp group. Semi-structured focus groups investigated student perspectives on the acceptability and impact of v-logging on their reflective practice. We thematically analysed transcripts of the WhatsApp conversations and two focus groups.Students felt v-logging was more engaging and convenient than written reflections. V-logging was found to enhance emotional content that is commonly lacking in written reflection, which is has importance as emotional recognition promotes a higher quality of reflection. Although some students were concerned about their appearance in videos, they appeared to overcome this, finding v-logging facilitated deeper reflection compared with traditional written reflections due to accessibility and ease of expression. Furthermore, there was additional learning through watching other students’ emotive vlogs which fits with the phenomenon of reflective vicarious learning.Sharing vlogs within a WhatsApp group appeared to be an accessible way for facilitating greater engagement with affective and expressive aspects of reflection

Isolation of Mycobacterium avium from Potable Water in Homes and Institutions of Patients with HIV Infection in Finland and the United States

Symptomatic disease by nontuberculous mycobacteria has been linked to potable water from institutional and domestic potable water systems. Potable water samples were collected from homes and institutions of patients with AIDS. Colonization of potable water with nontuberculous mycobacteria was demonstrated in 230 (15%) of 1489 samples collected from domestic and institutional water systems of patients with HIV infection in the United States and Finland. Mycobacterium avium was the most common species and colonization was favored at temperatures of 40-50 degrees C in recirculating hot water systems. Such systems are a plausible source of human infection and disease.Peer reviewe