The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor.

Mammalian Toll-like receptors (TLRs) 3, 7, 8 and 9 initiate immune responses to infection by recognizing microbial nucleic acids; however, these responses come at the cost of potential autoimmunity owing to inappropriate recognition of self nucleic acids. The localization of TLR9 and TLR7 to intracellular compartments seems to have a role in facilitating responses to viral nucleic acids while maintaining tolerance to self nucleic acids, yet the cell biology regulating the transport and localization of these receptors remains poorly understood. Here we define the route by which TLR9 and TLR7 exit the endoplasmic reticulum and travel to endolysosomes in mouse macrophages and dendritic cells. The ectodomains of TLR9 and TLR7 are cleaved in the endolysosome, such that no full-length protein is detectable in the compartment where ligand is recognized. Notably, although both the full-length and cleaved forms of TLR9 are capable of binding ligand, only the processed form recruits MyD88 on activation, indicating that this truncated receptor, rather than the full-length form, is functional. Furthermore, conditions that prevent receptor proteolysis, including forced TLR9 surface localization, render the receptor non-functional. We propose that ectodomain cleavage represents a strategy to restrict receptor activation to endolysosomal compartments and prevent TLRs from responding to self nucleic acids

Head Start and child care providers’ motivators, barriers and facilitators to practicing family-style meal service

This paper presents a qualitative investigation of the motivators, barriers, and facilitators for practicing family-style meal service (FSMS) from the perspective of 18 child care providers serving preschool children in Head Start (HS), Child and Adult Care Food Program (CACFP) funded, and non-CACFP child-care centers. Providers were selected based on maximum variation purposive sampling and semi-structured interviews were conducted until saturation was reached. Provider responses were systematically coded using thematic analysis. HS and CACFP providers reported being motivated to practice FSMS because it created pleasant mealtimes, opportunities to role model healthy eating, and healthful child development. CACFP and non-CACFP providers reported not using FSMS because it was resource intensive, messy, and seemed to violate CACFP policy. HS and CACFP providers offered suggestions to overcome these barriers. They suggested that FSMS eventually becomes easier with practice, children can self-regulate their energy intake, and teaching children self-help skills during play time can avoid messes during mealtimes. Findings from this study have implications for programming, policy, and research

Comparison of 3-Factor Prothrombin Complex Concentrate and Low-Dose Recombinant Factor VIIa for Warfarin Reversal

INTRODUCTION: Prothrombin complex concentrate (PCC) and recombinant Factor VIIa (rFVIIa) have been used for emergent reversal of warfarin anticoagulation. Few clinical studies have compared these agents in warfarin reversal. We compared warfarin reversal in patients who received either 3 factor PCC (PCC3) or low-dose rFVIIa (LDrFVIIa) for reversal of warfarin anticoagulation. METHODS: Data were collected from medical charts of patients who received at least one dose of PCC3 (20 units/kg) or LDrFVIIa (1000 or 1200 mcg) for emergent warfarin reversal from August 2007 to October 2011. The primary end-points were achievement of an INR 1.5 or less for efficacy and thromboembolic events for safety. RESULTS: Seventy-four PCC3 and 32 LDrFVIIa patients were analyzed. Baseline demographics, reason for warfarin reversal, and initial INR were equivalent. There was no difference in the use of vitamin K or fresh frozen plasma. More LDrFVIIa patients achieved an INR of 1.5 or less (71.9% vs. 33.8%, p =0.001). The follow-up INR was lower after LDrFVIIa (1.25 vs. 1.75, p < 0.05) and the percent change in INR was larger after LDrFVIIa (54.1% vs. 38.8%, p = 0.002). There was no difference in the number of thromboembolic events (2 LDrFVIIa vs. 5 PCC3, p = 1.00), mortality, length of hospital stay, or cost. CONCLUSIONS: Based on achieving a goal INR of 1.5 or less, LDrFVIIa was more likely than PCC3 to reverse warfarin anticoagulation. Thromboembolic events were equivalent in patients receiving PCC3 and LDrFVIIa

Limiting motorboat noise on coral reefs boosts fish reproductive success

Anthropogenic noise impacts are pervasive across taxa, ecosystems and the world. Here, we experimentally test the hypothesis that protecting vulnerable habitats from noise pollution can improve animal reproductive success. Using a season-long field manipulation with an established model system on the Great Barrier Reef, we demonstrate that limiting motorboat activity on reefs leads to the survival of more fish offspring compared to reefs experiencing busy motorboat traffic. A complementary laboratory experiment isolated the importance of noise and, in combination with the field study, showed that the enhanced reproductive success on protected reefs is likely due to improvements in parental care and offspring length. Our results suggest noise mitigation could have benefits that carry through to the population-level by increasing adult reproductive output and offspring growth, thus helping to protect coral reefs from human impacts and presenting a valuable opportunity for enhancing ecosystem resilience

Social contacts, vaccination decisions and influenza in Japan.

BACKGROUND: Contact patterns and vaccination decisions are fundamental to transmission dynamics of infectious diseases. We report on age-specific contact patterns in Japan and their effect on influenza vaccination behaviour. METHODS: Japanese adults (N=3146) were surveyed in Spring 2011 to assess the number of their social contacts within a 24 h period, defined as face-to-face conversations within 2 m, and gain insight into their influenza-related behaviour. We analysed the duration and location of contacts according to age. Additionally, we analysed the probability of vaccination and influenza infection in relation to the number of contacts controlling for individual's characteristics. RESULTS: The mean and median reported numbers of daily contacts were 15.3 and 12.0, respectively. School-aged children and young adults reported the greatest number of daily contacts, and individuals had the most contacts with those in the same age group. The age-specific contact patterns were different between men and women, and differed between weekdays and weekends. Children had fewer contacts between the same age groups during weekends than during weekdays, due to reduced contacts at school. The probability of vaccination increased with the number of contacts, controlling for age and household size. Influenza infection among unvaccinated individuals was higher than for those vaccinated, and increased with the number of contacts. CONCLUSIONS: Contact patterns in Japan are age and gender specific. These contact patterns, as well as their interplay with vaccination decisions and infection risks, can help inform the parameterisation of mathematical models of disease transmission and the design of public health policies, to control disease transmission

How puzzles are shaping our understanding of biodiversity: A call for more research into biodiversity representation in educational games

Games as a didactic tool (e. g., puzzles) are gaining recognition in environmental education to promote skill development, but also to develop a specific understanding of the natural world. However, a children’s puzzle containing representations of nature may unwillingly lead to “misconceptions” of biodiversity themes and processes, and an over-simplification of the relationship between people and nature. To solve this problem, positive connotations of biodiversity may prompt a conceptual change to a more nuanced, multifaceted conception of biodiversity

Homogenization via formal multiscale asymptotics and volume averaging: How do the two techniques compare?

A wide variety of techniques have been developed to homogenize transport equations in multiscale and multiphase systems. This has yielded a rich and diverse field, but has also resulted in the emergence of isolated scientific communities and disconnected bodies of literature. Here, our goal is to bridge the gap between formal multiscale asymptotics and the volume averaging theory. We illustrate the methodologies via a simple example application describing a parabolic transport problem and, in so doing, compare their respective advantages/disadvantages from a practical point of view. This paper is also intended as a pedagogical guide and may be viewed as a tutorial for graduate students as we provide historical context, detail subtle points with great care, and reference many fundamental works

A 680,000-person megastudy of nudges to encourage vaccination in pharmacies

Encouraging vaccination is a pressing policy problem. To assess whether text-based reminders can encourage pharmacy vaccination and what kinds of messages work best, we conducted a megastudy. We randomly assigned 689,693 Walmart pharmacy patients to receive one of 22 different text reminders using a variety of different behavioral science principles to nudge flu vaccination or to a business-as-usual control condition that received no messages. We found that the reminder texts that we tested increased pharmacy vaccination rates by an average of 2.0 percentage points, or 6.8%, over a 3-mo follow-up period. The most-effective messages reminded patients that a flu shot was waiting for them and delivered reminders on multiple days. The top-performing intervention included two texts delivered 3 d apart and communicated to patients that a vaccine was “waiting for you.” Neither experts nor lay people anticipated that this would be the best-performing treatment, underscoring the value of simultaneously testing many different nudges in a highly powered megastudy