The multifunctional poly(A)-binding protein (PABP) 1 is subject to extensive dynamic post-translational modification, which molecular modelling suggests plays an important role in co-ordinating its activities

PABP1 [poly(A)-binding protein 1] is a central regulator of mRNA translation and stability and is required for miRNA (microRNA)-mediated regulation and nonsense-mediated decay. Numerous protein, as well as RNA, interactions underlie its multi-functional nature; however, it is unclear how its different activities are co-ordinated, since many partners interact via overlapping binding sites. In the present study, we show that human PABP1 is subject to elaborate post-translational modification, identifying 14 modifications located throughout the functional domains, all but one of which are conserved in mouse. Intriguingly, PABP1 contains glutamate and aspartate methylations, modifications of unknown function in eukaryotes, as well as lysine and arginine methylations, and lysine acetylations. The latter dramatically alter the pI of PABP1, an effect also observed during the cell cycle, suggesting that different biological processes/stimuli can regulate its modification status, although PABP1 also probably exists in differentially modified subpopulations within cells. Two lysine residues were differentially acetylated or methylated, revealing that PABP1 may be the first example of a cytoplasmic protein utilizing a ‘methylation/acetylation switch’. Modelling using available structures implicates these modifications in regulating interactions with individual PAM2 (PABP-interacting motif 2)-containing proteins, suggesting a direct link between PABP1 modification status and the formation of distinct mRNP (messenger ribonucleoprotein) complexes that regulate mRNA fate in the cytoplasm

Developing an alcohol and other drug serious game for adolescents: Considerations for improving student engagement

Objectives: To explore perceptions of alcohol and other drug (AOD) education and digital game design preferences among Australian adolescents with the goal of identifying key factors to promote engagement in an AOD serious game for Australian secondary school students. Methods: Semi-structured focus groups were conducted with 36 adolescents aged between 13 and 18 years. Qualitative data was analysed using thematic analysis. Results: Participants described heightened engagement with AOD education that incorporated relatable and relevant real-life stories and interactive discussions. They also expressed a desire for learning to focus on practical strategies to reduce AOD harm and overcome social pressure to use AOD. Participants highlighted the importance of incorporating relatable characters and context-relevant scenarios in promoting engagement, and identified social elements, player choice, and optimal challenge as important game design considerations. Conclusions: A focus on meaningful realistic scenarios, relatable characters, relevant information and practical skills may promote high school aged students’ engagement with AOD educational content. Game designs incorporating social elements and decision-making opportunities may be conducive to promoting engagement and enhancing learning. Implications for public health: Findings from this study can be used by researchers and game designers for the development of future AOD serious games targeted at Australian adolescents

Exposure to Household Air Pollution from Biomass Cookstoves and Blood Pressure Among Women in Rural Honduras: A Cross‐Sectional Study

Growing evidence links household air pollution exposure from biomass cookstoves with elevated blood pressure. We assessed cross‐sectional associations of 24‐hour mean concentrations of personal and kitchen fine particulate matter (PM2.5), black carbon (BC), and stove type with blood pressure, adjusting for confounders, among 147 women using traditional or cleaner‐burning Justa stoves in Honduras. We investigated effect modification by age and body mass index. Traditional stove users had mean (standard deviation) personal and kitchen 24‐hour PM2.5 concentrations of 126 μg/m3 (77) and 360 μg/m3 (374), while Justa stove users’ exposures were 66 μg/m3 (38) and 137 μg/m3(194), respectively. BC concentrations were similarly lower among Justa stove users. Adjusted mean systolic blood pressure was 2.5 mm Hg higher (95% CI, 0.7‐4.3) per unit increase in natural log‐transformed kitchen PM2.5 concentration; results were stronger among women of 40 years or older (5.2 mm Hg increase, 95% CI, 2.3‐8.1). Adjusted odds of borderline high and high blood pressure (categorized) were also elevated (odds ratio = 1.5, 95% CI, 1.0‐2.3). Some results included null values and are suggestive. Results suggest that reduced household air pollution, even when concentrations exceed air quality guidelines, may help lower cardiovascular disease risk, particularly among older subgroups

Beam tests of a large-scale TORCH time-of-flight demonstrator

The TORCH time-of-flight detector is designed to provide particle identification in the momentum range 2-10 GeV/c over large areas. The detector exploits prompt Cherenkov light produced by charged particles traversing a 10 mm thick quartz plate. The photons propagate via total internal reflection and are focused onto a detector plane comprising position-sensitive Micro-Channel Plate Photo-Multiplier Tubes (MCP-PMT) detectors. The goal is to achieve a single-photon timing resolution of 70 ps, giving a timing precision of 15 ps per charged particle by combining the information from around 30 detected photons. The MCP-PMT detectors have been developed with a commercial partner (Photek Ltd, UK), leading to the delivery of a square tube of active area 53 $\times$ 53mm$^2$ with a granularity of 8 $\times$ 128 pixels equivalent. A large-scale demonstrator of TORCH, having a quartz plate of dimensions 660 $\times$ 1250 $\times$ 10 mm$^3$ and read out by a pair of MCP-PMTs with custom readout electronics, has been verified in a test beam campaign at the CERN PS. Preliminary results indicate that the required performance is close to being achieved. The anticipated performance of a full-scale TORCH detector at the LHCb experiment is presented.Comment: 12 pages, 7 figures, Paper submitted to Nuclear Instruments & Methods in Physics Research, Section A - Special Issue VCI 201

Study Protocol for a Stepped-Wedge Randomized Cookstove Intervention in Rural Honduras: Household Air Pollution and Cardiometabolic Health

Growing evidence links household air pollution exposure from biomass-burning cookstoves to cardiometabolic disease risk. Few randomized controlled interventions of cookstoves (biomass or otherwise) have quantitatively characterized changes in exposure and indicators of cardiometabolic health, a growing and understudied burden in low- and middle-income countries (LMICs). Ideally, the solution is to transition households to clean cooking, such as with electric or liquefied petroleum gas stoves; however, those unable to afford or to access these options will continue to burn biomass for the foreseeable future. Wood-burning cookstove designs such as the Justa (incorporating an engineered combustion zone and chimney) have the potential to substantially reduce air pollution exposures. Previous cookstove intervention studies have been limited by stove types that did not substantially reduce exposures and/or by low cookstove adoption and sustained use, and few studies have incorporated community-engaged approaches to enhance the intervention

Exposure to Household Air Pollution from Biomass Cookstoves and Levels of Fractional Exhaled Nitric Oxide (FeNO) among Honduran Women

Household air pollution is estimated to be responsible for nearly three million premature deaths annually. Measuring fractional exhaled nitric oxide (FeNO) may improve the limited understanding of the association of household air pollution and airway inflammation. We evaluated the cross-sectional association of FeNO with exposure to household air pollution (24-h average kitchen and personal fine particulate matter and black carbon; stove type) among 139 women in rural Honduras using traditional stoves or cleaner-burning Justastoves. We additionally evaluated interaction by age. Results were generally consistent with a null association; we did not observe a consistent pattern for interaction by age. Evidence from ambient and household air pollution regarding FeNO is inconsistent, and may be attributable to differing study populations, exposures, and FeNO measurement procedures (e.g., the flow rate used to measure FeNO)

Sideffect GamePlan: Development of an alcohol and other drug serious game for high school students using a systematic and iterative user-centred game development framework

Serious games have shown to be effective in improving motivation to learn, knowledge and retention, thus are being increasingly used for alcohol and other drug (AOD) education. This paper outlines the development of an online AOD serious game for in-class use by Australian secondary school teachers for students in Years 9–10. Adapted from Edwards et al. (2018), the seven-step systematic and iterative user-centred development framework included: (1) Forming an expert multidisciplinary design team, (2) Defining the problem and establishing user preferences, (3) Incorporating the evidence base, (4) Serious game design, (5) Incorporating behavioural and psychological theory, (6) Developing a logic model and investigating causal pathways, and (7) User testing. High school students (n = 8), health and physical education teachers (n = 7), and parents (n = 8) were engaged throughout different stages of the development process to inform development and provide feedback on considerations for promoting engagement, acceptability, and usability of the game amongst both students and teachers. Overall, participants rated game acceptability and usability favourably and would recommend the game for learning about AOD. Constructive feedback and suggestions for improvements from user testing sessions were implemented to form the final version of the game and module. The next step is to test Sideffect GamePlan in a simulated classroom environment before piloting in school settings