Light thresholds for seagrasses of the GBRWHA: a synthesis and guiding document

[Extract]. Key Findings. This synthesis contains light thresholds for seagrass species in the Great Barrier Reef World Heritage Area (GBRWHA). The thresholds can be applied to ensure protection of seagrasses from activities that impact water quality and the light environment over the short-term, such as coastal and port developments. Thresholds for long-term maintenance of seagrasses are also proposed. •The synthesis provides clear and consistent guidance on light thresholds to apply in managing potential water quality impacts to seagrass. •All available information on biological light thresholds was tabulated and conservative management thresholds were identified to ensure seagrass protection. •Acute management thresholds are suited to compliance guidelines for managing short-term impacts and these and are the focus of this synthesis. Long-term thresholds are suited to the setting of water quality guidelines for catchment management. •The synthesis identified key areas where further information is required, including: ◦species for which almost no information on light thresholds exists; ◦location and population-specific thresholds particularly for the most at-risk species; ◦definitions of desired state to underpin the development of long-term light guidelines to meet them; ◦the effect of spectral quality on light thresholds; and, consideration of cumulative impacts (temperature, nutrients, sedimentary conditions) on acute and long-term light thresholds. •Light management thresholds for acute impacts are presented for twelve species. Colonising species are the most sensitive to light reduction (i.e. lowest thresholds) and have the shortest time to impact while larger, persistent species have higher light thresholds and a longer time to impact. •The recommended acute management thresholds are ready for application, as the conservative approach (higher light threshold, shortest time to impact) for species with low confidence should ensure protection to seagrass meadows at risk from acute light stress

Photocrosslinking Activity-Based Probes for Ubiquitin RING E3 Ligases

Summary: Activity-based protein profiling is an invaluable technique for studying enzyme biology and facilitating the development of therapeutics. Ubiquitin E3 ligases (E3s) are one of the largest enzyme families and regulate a host of (patho)physiological processes. The largest subtype are the RING E3s of which there are >600 members. RING E3s have adaptor-like activity that can be subject to diverse regulatory mechanisms and have become attractive drug targets. Activity-based probes (ABPs) for measuring RING E3 activity do not exist. Here we re-engineer ubiquitin-charged E2 conjugating enzymes to produce photocrosslinking ABPs. We demonstrate activity-dependent profiling of two divergent cancer-associated RING E3s, RNF4 and c-Cbl, in response to their native activation signals. We also demonstrate profiling of endogenous RING E3 ligase activation in response to epidermal growth factor (EGF) stimulation. These photocrosslinking ABPs should advance E3 ligase research and the development of selective modulators against this important class of enzymes

Preferences for simultaneous polydrug use: a comparative study of young adults in England and Denmark

Cross-national surveys of young adults’ simultaneous polydrug use (SPU) are rare, as measuring polydrug use requires multiple questions capturing the timing, sequence, and dosage of mixing drugs. This study proposes a new way of measuring SPU by examining how preferences for simultaneous polydrug use (PSPU) vary among club/bar-goers in two European countries, Denmark and England, typically cited as exemplars of the normalization of illegal drug use. The study considers the utility of the normalization thesis for understanding preferences for polydrug use in the European nighttime economy. An in situ survey of 1,298 young adults (18–35 years) conducted in 50 bars, pubs, and nightclubs in England and Denmark assessed sociodemographics, substance use patterns, and personal preference(s) for mixing alcohol and drug use. Multinomial regression analyses examined the relative risk of PSPU categories among those reporting drug use, according to sociodemographics, alcohol intake, frequency of intoxication, and smoking. Illicit drug use was more prevalent among young adults in England than Denmark. The difference was smallest for cannabis use: Lifetime cannabis use is 66% in England and 58% in Denmark. Lifetime cocaine use was 38% in England and 17% in Denmark. In England, young adults with drug experience preferred to mix alcohol with cocaine (65%). In Denmark, young adults with drug experience preferred to mix alcohol with cannabis (78%). In multinominal regression, Danish young adults’ educational level was associated with PSPU, whereas in England legal substance use was associated with PSPU. This study calls for a more differentiated understanding of normalization. Preferences for mixing alcohol and drug use varied significantly cross nationally (alcohol/cocaine, England; alcohol/cannabis, Denmark). Different factors are associated with PSPU in each country. In England, not Denmark, drinking behaviors appear to shape preferences for mixing alcohol with cocaine, suggesting caution should be taken when replicating harm reduction intervention

Cellular IP₆ Levels Limit HIV Production while Viruses that Cannot Efficiently Package IP₆ Are Attenuated for Infection and Replication

Summary: HIV-1 hijacks host proteins to promote infection. Here we show that HIV is also dependent upon the host metabolite inositol hexakisphosphate (IP6) for viral production and primary cell replication. HIV-1 recruits IP6 into virions using two lysine rings in its immature hexamers. Mutation of either ring inhibits IP6 packaging and reduces viral production. Loss of IP6 also results in virions with highly unstable capsids, leading to a profound loss of reverse transcription and cell infection. Replacement of one ring with a hydrophobic isoleucine core restores viral production, but IP6 incorporation and infection remain impaired, consistent with an independent role for IP6 in stable capsid assembly. Genetic knockout of biosynthetic kinases IPMK and IPPK reveals that cellular IP6 availability limits the production of diverse lentiviruses, but in the absence of IP6, HIV-1 packages IP5 without loss of infectivity. Together, these data suggest that IP6 is a critical cofactor for HIV-1 replication

The First Brown Dwarf Discovered by the Backyard Worlds: Planet 9 Citizen Science Project

The Wide-field Infrared Survey Explorer (WISE) is a powerful tool for finding nearby brown dwarfs and searching for new planets in the outer solar system, especially with the incorporation of NEOWISE and NEOWISE-Reactivation data. So far, searches for brown dwarfs in WISE data have yet to take advantage of the full depth of the WISE images. To efficiently search this unexplored space via visual inspection, we have launched a new citizen science project, called "Backyard Worlds: Planet 9," which asks volunteers to examine short animations composed of difference images constructed from time-resolved WISE coadds. We report the discovery of the first new substellar object found by this project, WISEA J110125.95+540052.8, a T5.5 brown dwarf located approximately 34 pc from the Sun with a total proper motion of $\sim$0.7 as yr$^{-1}$. WISEA J110125.95+540052.8 has a WISE $W2$ magnitude of $W2=15.37 \pm 0.09$, this discovery demonstrates the ability of citizen scientists to identify moving objects via visual inspection that are 0.9 magnitudes fainter than the $W2$ single-exposure sensitivity, a threshold that has limited prior motion-based brown dwarf searches with WISE.Comment: 9 pages, 4 figures, 1 table. Accepted for publication in the Astrophysical Journal Letter

Health improvement and educational attainment in secondary schools: complementary or competing priorities? Exploratory analyses from the School Health Research Network in Wales

Background. Implementing health improvement is often perceived as diverting resource away from schools’ core business, reflecting an assumption of a “zero-sum game” between health and education. There is some evidence that health behaviors may affect young people’s educational outcomes. However, associations between implementation of school health improvement and educational outcomes remains underinvestigated. Methods. The study linked school-level data on free school meal (FSM) entitlement, educational outcomes, and school attendance, obtained from government websites, with data from the School Environment Questionnaire (SEQ) on health improvement activity collected in Wales (2015/2016). Spearman’s rank correlation coefficients and linear regression models tested the extent of association between health improvement activity and attendance and educational outcomes. Results. SEQ data were provided by 100/115 network schools (87%), of whom data on educational performance were obtained from 97. The percentage of pupils entitled to FSM predicted most of the between-school variance in achievement and attendance. Linear regression models demonstrated significant positive associations of all measures of health improvement activity with attainment at Key Stage (KS) 3, apart from mental health education in the curriculum and organizational commitment to health. Student and parent involvement in planning health activities were associated with improved school attendance. There were no significant associations between health improvement and KS4 attainment. Conclusion. Implementing health improvement activity does not have a detrimental effect on schools’ educational performance. There is tentative evidence of the reverse, with better educational outcomes in schools with more extensive health improvement policies and practices. Further research should investigate processes by which this occurs and variations by socioeconomic status

Testing the ‘zero-sum game’ hypothesis: An examination of school health policies and practices and inequalities in educational outcomes

Background There is recognition that health and education are intrinsically linked through, for example, WHO's Health Promoting Schools (HPS) framework. Nevertheless, promoting health via schools is seen by some as a zero-sum game—ie, schools have nothing to gain, and may experience detriments to the core business of academic attainment because of focusing resources on health. Crucially, there is a paucity of evidence around the impacts of health and wellbeing policy and practice on attainment, with recent Cochrane reviews highlighting this gap. This study explored the zero-sum game hypothesis among schools with varying levels of deprivation—ie, the role of health and wellbeing interventions in schools in reducing or widening socioeconomic inequality in educational attainment. Methods Wales-wide, school-level survey data on health policies and practices, reflective of the HPS framework, were captured in 2016 using the School Environment Questionnaire. Questionnaire data were linked with routinely collected data on academic attainment. Primary outcomes included attendance and attainment at Key stages 3 (children aged 12–14 years) and 4 (15–16). Interaction terms were fitted to test whether there was an interaction between free school meals, overall HPS activity, and outcomes. Linear regression models were constructed separately for schools with high uptake of free school meals (>15% of pupils) and low uptake (<15%), adjusting for confounders. Findings The final analyses included 48 schools with low uptake of free school meals and 49 with high uptake. Significant interactions were observed between free school meals and overall HPS activity for Key stage 3 attainment (β=0·28, 95% CI 0·09–0·47) and attendance (0·05, 0·02–0·09), reflecting an association between health improvement activities and education outcomes among high, but not low, free school meal schools. There was no significant interaction for Key stage 4 attainment (0·18, −0·22 to 0·57). Interpretation Our findings did not support the zero-sum game hypothesis; in fact, among more deprived schools, there was a tendency for better attendance and attainment at Key stage 3. Schools must equip students with the skills required for good physical and mental health and wellbeing in addition to academic and cognitive skills. The study included a large, nationally representative sample of secondary schools; however, the cross-sectional nature has implications for causality

The F-CHROMA grid of 1D RADYN flare models

Context: Solar flares are the result of the sudden release of magnetic energy in the corona. Much of this energy goes into accelerating charged particles to high velocity. These particles travel along the magnetic field and the energy is dissipated when the density gets high enough, primarily in the solar chromosphere. Modelling this region is difficult because the radiation energy balance is dominated by strong, optically thick spectral lines. Aims: Our aim is to provide the community with realistic simulations of a flaring loop with an emphasis on the detailed treatment of the chromospheric energy balance. This will enable a detailed comparison of existing and upcoming observations with synthetic observables from the simulations, thereby elucidating the complex interactions in a flaring chromosphere. Methods: We used the 1D radiation hydrodynamics code RADYN to perform simulations of the effect of a beam of electrons injected at the apex of a solar coronal loop. A grid of models was produced, varying the total energy input, the steepness, and low-energy cutoff of the beam energy spectrum. Results: The full simulation results for a grid of models are made available online. Some general properties of the simulations are discussed.Comment: 11 pages, 9 figures. Accepted for publication in Astronomy & Astrophysic

Deubiquitinating enzyme amino acid profiling reveals a class of ubiquitin esterases

The reversibility of ubiquitination by the action of deubiquitinating enzymes (DUBs) serves as an important regulatory layer within the ubiquitin system. Approximately 100 DUBs are encoded by the human genome, and many have been implicated with pathologies, including neurodegeneration and cancer. Non-lysine ubiquitination is chemically distinct, and its physiological importance is emerging. Here, we couple chemically and chemoenzymatically synthesized ubiquitinated lysine and threonine model substrates to a mass spectrometry-based DUB assay. Using this platform, we profile two-thirds of known catalytically active DUBs for threonine esterase and lysine isopeptidase activity and find that most DUBs demonstrate dual selectivity. However, with two anomalous exceptions, the ovarian tumor domain DUB class demonstrates specific (iso)peptidase activity. Strikingly, we find the Machado–Joseph disease (MJD) class to be unappreciated non-lysine DUBs with highly specific ubiquitin esterase activity rivaling the efficiency of the most active isopeptidases. Esterase activity is dependent on the canonical catalytic triad, but proximal hydrophobic residues appear to be general determinants of non-lysine activity. Our findings also suggest that ubiquitin esters have appreciable cellular stability and that non-lysine ubiquitination is an integral component of the ubiquitin system. Its regulatory sophistication is likely to rival that of canonical ubiquitination.We thank Axel Knebel, Richard Ewan, Clare Johnson, and Daniel Fountaine from the Medical Research Council (MRC) Protein Production and Assay Development team, and MRC Reagents and Services, who all contributed to the generation of protein reagents required for the MALDI-TOF DUB assay platform. We thank Ronald Hay for provision of the plasmid encoding the constitutively active RNF4 E3 ligase. This work was funded by the United Kingdom MRC (MC_UU_12016/8), the Biotechnology and Biological Sciences Research Council (BB/P003982/1), and The Michael J. Fox Foundation (12756). We also acknowledge pharmaceutical companies supporting the Division of Signal Transduction Therapy (Boehringer-Ingelheim, GlaxoSmithKline, and Merck KGaA).Peer reviewe