Tetraspanins regulate cell-to-cell transmission of HIV-1

<p>Abstract</p> <p>Background</p> <p>The presence of the tetraspanins CD9, CD63, CD81 and CD82 at HIV-1 budding sites, at the virological synapse (VS), and their enrichment in HIV-1 virions has been well-documented, but it remained unclear if these proteins play a role in the late phase of the viral replication cycle. Here we used overexpression and knockdown approaches to address this question.</p> <p>Results</p> <p>Neither ablation of CD9, CD63 and/or CD81, nor overexpression of these tetraspanins was found to affect the efficiency of virus release. However, confirming recently reported data, tetraspanin overexpression in virus-producing cells resulted in the release of virions with substantially reduced infectivity. We also investigated the roles of these tetraspanins in cell-to-cell transmission of HIV-1. Overexpression of CD9 and CD63 led to reduced cell-to-cell transmission of this virus. Interestingly, in knockdown experiments we found that ablation of CD63, CD9 and/or CD81 had no effect on cell-free infectivity. However, knockdown of CD81, but not CD9 and CD63, enhanced productive particle transmission to target cells, suggesting additional roles for tetraspanins in the transmission process. Finally, tetraspanins were found to be downregulated in HIV-1-infected T lymphocytes, suggesting that HIV-1 modulates the levels of these proteins in order to maximize the efficiency of its transmission within the host.</p> <p>Conclusion</p> <p>Altogether, these results establish an active role of tetraspanins in HIV-1 producer cells.</p

Addressing fidelity within complex health behaviour change interventions: A protocol of a scoping review of intervention fidelity frameworks and models

Intervention fidelity is crucial to facilitate accurate interpretation of research outcomes, but has been inadequately addressed within complex health behaviour change interventions. Recent research has highlighted a need for practical guidance to improve understanding and use of existing fidelity frameworks and models within complex health behaviour change intervention research. The aim of this paper is to present a protocol for a scoping review of existing intervention fidelity frameworks and models. // In accordance with scoping review guidelines, the following stages will be conducted: (1) identifying the research question, (2) identifying potentially relevant studies of fidelity frameworks and models, (3) study screening and selection, (4) charting and extracting data from identified frameworks and models, (5) collating, summarising and reporting the results and (6) consultation with stakeholders. Two reviewers will independently conduct the screening and extraction stages. Identified frameworks will be collated, summarized and categorized iteratively by one reviewer in consultation with the review team. // The findings of this review will provide a useful resource by identifying and comparing existing fidelity frameworks and models. It is intended that increased clarity and understanding in this area will facilitate the appropriate selection and application of fidelity frameworks for complex health behaviour change interventions, inform areas for future research, and ultimately contribute towards improving how intervention fidelity is addressed in this area

General Messenger Gauge Mediation

We discuss theories of gauge mediation in which the hidden sector consists of two subsectors which are weakly coupled to each other. One sector is made up of messengers and the other breaks supersymmetry. Each sector by itself may be strongly coupled. We provide a unifying framework for such theories and discuss their predictions in different settings. We show how this framework incorporates all known models of messengers. In the case of weakly-coupled messengers interacting with spurions through the superpotential, we prove that the sfermion mass-squared is positive, and furthermore, that there is a lower bound on the ratio of the sfermion mass to the gaugino mass.Comment: 37 pages; minor change

Early High-Dose Vitamin D3 for Critically Ill, Vitamin D-Deficient Patients

BACKGROUND: Vitamin D deficiency is a common, potentially reversible contributor to morbidity and mortality among critically ill patients. The potential benefits of vitamin D supplementation in acute critical illness require further study. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial of early vitamin D3 supplementation in critically ill, vitamin D-deficient patients who were at high risk for death. Randomization occurred within 12 hours after the decision to admit the patient to an intensive care unit. Eligible patients received a single enteral dose of 540,000 IU of vitamin D3 or matched placebo. The primary end point was 90-day all-cause, all-location mortality. RESULTS: A total of 1360 patients were found to be vitamin D-deficient during point-of-care screening and underwent randomization. Of these patients, 1078 had baseline vitamin D deficiency (25-hydroxyvitamin D level,[50 nmol per liter]) confirmed by subsequent testing and were included in the primary analysis population. The mean day 3 level of 25-hydroxyvitamin D was 46.9±23.2 ng per milliliter (117±58 nmol per liter) in the vitamin D group and 11.4±5.6 ng per milliliter (28±14 nmol per liter) in the placebo group (difference, 35.5 ng per milliliter; 95% confidence interval [CI], 31.5 to 39.6). The 90-day mortality was 23.5% in the vitamin D group (125 of 531 patients) and 20.6% in the placebo group (109 of 528 patients) (difference, 2.9 percentage points; 95% CI, -2.1 to 7.9; P = 0.26). There were no clinically important differences between the groups with respect to secondary clinical, physiological, or safety end points. The severity of vitamin D deficiency at baseline did not affect the association between the treatment assignment and mortality. CONCLUSIONS: Early administration of high-dose enteral vitamin D3 did not provide an advantage over placebo with respect to 90-day mortality or other, nonfatal outcomes among critically ill, vitamin D-deficient patients. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial of early vitamin D3 supplementation in critically ill, vitamin D-deficient patients who were at high risk for death. Randomization occurred within 12 hours after the decision to admit the patient to an intensive care unit. Eligible patients received a single enteral dose of 540,000 IU of vitamin D3 or matched placebo. The primary end point was 90-day all-cause, all-location mortality

Ocean convergence and the dispersion of flotsam

Floating oil, plastics, and marine organisms are continually redistributed by ocean surface currents. Prediction of their resulting distribution on the surface is a fundamental, long-standing, and practically important problem. The dominant paradigm is dispersion within the dynamical context of a nondivergent flow: objects initially close together will on average spread apart but the area of surface patches of material does not change. Although this paradigm is likely valid at mesoscales, larger than 100 km in horizontal scale, recent theoretical studies of submesoscales (less than ∼10 km) predict strong surface convergences and downwelling associated with horizontal density fronts and cyclonic vortices. Here we show that such structures can dramatically concentrate floating material. More than half of an array of ∼200 surface drifters covering ∼20 × 20 km2 converged into a 60 × 60 m region within a week, a factor of more than 105 decrease in area, before slowly dispersing. As predicted, the convergence occurred at density fronts and with cyclonic vorticity. A zipperlike structure may play an important role. Cyclonic vorticity and vertical velocity reached 0.001 s−1 and 0.01 ms−1, respectively, which is much larger than usually inferred. This suggests a paradigm in which nearby objects form submesoscale clusters, and these clusters then spread apart. Together, these effects set both the overall extent and the finescale texture of a patch of floating material. Material concentrated at submesoscale convergences can create unique communities of organisms, amplify impacts of toxic material, and create opportunities to more efficiently recover such material

Ocean convergence and the dispersion of flotsam

Floating oil, plastics, and marine organisms are continually redistributed by ocean surface currents. Prediction of their resulting distribution on the surface is a fundamental, long-standing, and practically important problem. The dominant paradigm is dispersion within the dynamical context of a nondivergent flow: objects initially close together will on average spread apart but the area of surface patches of material does not change. Although this paradigm is likely valid at mesoscales, larger than 100 km in horizontal scale, recent theoretical studies of submesoscales (less than ∼10 km) predict strong surface convergences and downwelling associated with horizontal density fronts and cyclonic vortices. Here we show that such structures can dramatically concentrate floating material. More than half of an array of ∼200 surface drifters covering ∼20 × 20 km2 converged into a 60 × 60 m region within a week, a factor of more than 105 decrease in area, before slowly dispersing. As predicted, the convergence occurred at density fronts and with cyclonic vorticity. A zipperlike structure may play an important role. Cyclonic vorticity and vertical velocity reached 0.001 s−1 and 0.01 ms−1, respectively, which is much larger than usually inferred. This suggests a paradigm in which nearby objects form submesoscale clusters, and these clusters then spread apart. Together, these effects set both the overall extent and the finescale texture of a patch of floating material. Material concentrated at submesoscale convergences can create unique communities of organisms, amplify impacts of toxic material, and create opportunities to more efficiently recover such material

Traveling waves for a model of gravity-driven film flows in cylindrical domains

Traveling wave solutions are studied for a recently-derived model of a falling viscous film on the interior of a vertical rigid tube. By identifying a Hopf bifurcation and using numerical continuation software, families of non-trivial traveling wave solutions may be traced out in parameter space. These families all contain a single solution at a ‘turnaround point’ with larger film thickness than all others in the family. In an earlier paper, it was conjectured that this turnaround point may represent a critical thickness separating two distinct flow regimes observed in physical experiments as well as two distinct types of behavior in transient solutions to the model. Here, these hypotheses are verified over a range of parameter values using a combination of numerical and analytical techniques. The linear stability of these solutions is also discussed; both large- and small-amplitude solutions are shown to be unstable, though the instability mechanisms are different for each wave type. Specifically, for small-amplitude waves, the region of relatively flat film away from the localized wave crest is subject to the same instability that makes the trivial flat-film solution unstable; for large-amplitude waves, this mechanism is present but dwarfed by a much stronger tendency to relax to a regime close to that followed by small-amplitude waves

The role of red and processed meat in colorectal cancer development : a perspective

Peer reviewe