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The red colouration of ripe chilli pepper fruit is due to the presence of the carotenoid capsanthin. 1-D-deoxy-xylulose 5-phosphate synthase (DXS) and phytoene synthase(s) (PSY) are influential biosynthetic steps in the carotenoid pathway. A panel of chilli accessions for varying fruit colour intensity revealed the correlation of carotenoid content withPSYandDXStranscript levels. ThePSYandDXSgenes were sequenced from high and low carotenoid genotypes to deduce potential allelic variation.PSY-1 and -2 showed tissue specific expression, withPSY-1and 2 expressed in chromoplast and chloroplast containing tissues, respectively. Protein modelling, phylogenetic analysis and transcription factor analysis was conducted to understand how the allelic variation identified could affect carotenoid biosynthesis and regulation, and subsequently colour intensity phenotype. A candidate mutation located in the transit peptide of the PSY-1 protein sequence was identified in the low colour intensity genotype. Within the promoter region of theDXSgene present in the high colour intensity genotype sequence variation was determined in the glyceraldehyde 3-phosphate binding motif (GAPF) of the promoter region. These data can be exploited to develop tools and resources for the breeding of high colour intensity chilli pepper fruit.Key policy highlightsUsing the molecular findings disclosed in this article the potential exists to develop molecular markers for the breeding varieties of chilli peppers with improved aesthetic consumer preference and nutritional attributes.

Funding Acknowledgements Type of funding sources: Other. Main funding source(s): 1. SHE Foundation and "la Caixa" 2. Fondo de Investigación Sanitaria - Instituto de Salud Carlos III. Background Family socioeconomic status (SES) impacts childhood health and could influence the effect of school-based health promotion interventions. Purpose This work aims to evaluate the impact of SES on the effects of the SI! Program randomized controlled trials for cardiovascular health promotion in preschoolers carried out in Colombia, Spain, and USA. Specifically, this work analyzed the effect of SES in the change of knowledge, attitudes and habits (KAH) and body mass index z-scores (zBMI) from baseline to immediately after the end of the health promotion intervention. Methods Children completed a KAH questionnaire (from 0 to 80 points) at baseline and immediate post-intervention. Families reported household income and education level through a dedicated questionnaire. Household income was categorized as low or high, and education level as low, intermediate, or high based on local census data. Adjusted baseline scores were calculated and stratified by SES using linear mixed models. The impact of the intervention was assessed by an individual participant-level meta-analysis using a random-effects model (DerSimonian-Laird method). Estimates of the difference between groups were derived from linear mixed models. Results A total of 3839 children were included in the analysis (48.9% girls, 4.0 (SD=0.8) years at baseline). Children of families with high education level and high household income tended to have a higher KAH score at baseline than those with low education level or low income (47.2 points [95%CI: 43.9; 50.5] vs. 45.7 points [95%CI: 42.4; 48.9]; 47.4 points [95%CI: 44.6; 50.2] vs. 45.8 points [95%CI: 43.0; 48.6], respectively) (Fig. 1A). Children from high education level and high income families had a lower zBMI at baseline than those from low education level and low income families (0.23 [95%CI: -0.20; 0.67] vs. 0.47 [95% CI: 0.03; 0.90]; 0.25 [95%CI: -0.15; 0.66] vs. 0.44 [95%CI: 0.04; 0.85], respectively) (Fig. 1B). The mean difference in KAH change between the intervention and control groups was 4.76 points (95%CI: 2.78; 6.74). The effect of the intervention on KAH score change was higher for children of families reporting high income or an intermediate/high education level than for those reporting low income or education level (Fig. 2A). The overall mean difference in zBMI change between groups was -0.06 (95%CI: -0.14; 0.02), and no significant differences were found in relation to SES indicators (Fig. 2B). Conclusions These results suggest that children from a low SES background benefit less from lifestyle interventions than those from high SES families. Health promotion interventions may implement strategies to counteract this effect and, consequently, avoid the potential risk of increasing health inequalities.

Enterococcus faecalis is a major causative agent of hospital acquired infections. The ability of E. faecalis to evade the host immune system is essential during pathogenesis, which has been shown to be dependent on the complete separation of daughter cells by peptidoglycan hydrolases. AtlE is a peptidoglycan hydrolase which is predicted to bind to the cell wall of E. faecalis, via six C-terminal repeat sequences. Here, we report the near complete assignment of one of these six repeats, as well as the predicted backbone structure and dynamics. This data will provide a platform for future NMR studies to explore the ligand recognition motif of AtlE and help to uncover its potential role in E. faecalis virulence.

Risk of conventional adenomas and serrated polyps at year 1 associated with categories of circulating serum high sensitivity C-reactive protein levels.

Ubiquitous and abundant in ecosystems and microbiomes, gokushoviruses constitute a Microviridae subfamily, distantly related to bacteriophages ΦX174, α3, and G4. A high-resolution cryo-EM structure of gokushovirus ΦEC6098 was determined, and the atomic model was built de novo. Although gokushoviruses lack external scaffolding and spike proteins, which extensively interact with the ΦX174 capsid protein, the core of the ΦEC6098 coat protein (VP1) displayed a similar structure. There are, however, key differences. At each ΦEC6098 icosahedral 3-fold axis, a long insertion loop formed mushroom-like protrusions, which have been noted in lower-resolution gokushovirus structures. Hydrophobic interfaces at the bottom of these protrusions may confer stability to the capsid shell. In ΦX174, the N-terminus of the capsid protein resides directly atop the 3-fold axes of symmetry; however, the ΦEC6098 N-terminus stretched across the inner surface of the capsid shell, reaching nearly to the 5-fold axis of the neighboring pentamer. Thus, this extended N-terminus interconnected pentamers on the inside of the capsid shell, presumably promoting capsid assembly, a function performed by the ΦX174 external scaffolding protein. There were also key differences between the ΦX174-like DNA-binding J proteins and its ΦEC6098 homologue VP8. As seen with the J proteins, C-terminal VP8 residues were bound into a pocket within the major capsid protein; however, its N-terminal residues were disordered, likely due to flexibility. We show that the combined location and interaction of VP8’s C-terminus and a portion of VP1’s N-terminus are reminiscent of those seen with the ΦX174 and α3 J proteins. IMPORTANCE There is a dramatic structural and morphogenetic divide within the Microviridae. The well-studied ΦX174-like viruses have prominent spikes at their icosahedral vertices, which are absent in gokushoviruses. Instead, gokushovirus major coat proteins form extensive mushroom-like protrusions at the 3-fold axes of symmetry. In addition, gokushoviruses lack an external scaffolding protein, the more critical of the two ΦX174 assembly proteins, but retain an internal scaffolding protein. The ΦEC6098 virion suggests that key external scaffolding functions are likely performed by coat protein domains unique to gokushoviruses. Thus, within one family, different assembly paths have been taken, demonstrating how a two-scaffolding protein system can evolve into a one-scaffolding protein system, or vice versa.

Background The UK Department for Work and Pensions (DWP) administers Universal Credit (UC) – the main UK benefit for people in- and out-of-work. UC is being rolled out nationally from 2013 to 2024. Citizens Advice (CA) is an independent charity that provides advice and support to people making a claim for UC. The aim of this study is to understand who is seeking advice from CA when making a UC claim and how the types of people seeking advice are changing as the rollout of UC continues. Methods Co-developed with Citizens Advice Newcastle and Citizens Advice Northumberland we performed longitudinal analysis of national data from Citizens Advice for England and Wales on the health (mental health and limiting long term conditions) and socio-demographic of 1,003,411 observations for people seeking advice with claiming UC over four financial years (2017/18 to 2020/21). We summarised population characteristics and estimated the differences between the four financial years using population-weighted t-tests. Findings were discussed with three people with lived experience of seeking advice to claim UC to help frame our interpretation and policy recommendations. Results When comparing 2017/18 to 2018/19, there was a significantly higher proportion of people with limiting long term conditions seeking advice with claiming UC than those without (+ 2.40%, 95%CI: 1.31%-3.50%). However as the rollout continued between 2018/29 and 2019/20 (-6.75%, 95%CI: -9.62%--3.88%) and between 2019/20 and 2020/21 (-2.09%, 95%CI: -2.54%--1.64%), there were significantly higher proportions of those without a limiting long term condition seeking advice than with. When comparing 2018/19 to 2019/20 and 2019/20 to 2020/21, there was a significant increase in the proportion of self-employed compared to unemployed people seeking advice with claiming UC (5.64%, 95%CI: 3.79%-7.49%) and (2.26%, 95%CI: 1.29%-3.23%) respectively. Conclusion As the rollout for UC continues, it is important to understand how changes in eligibility for UC may impact on those who need help with applying for UC. Ensuring that the advice process and application process is responsive to a range of people with different needs can help to reduce the likelihood that the process of claiming UC will exacerbate health inequalities.

Perovskites are of great technological and geological importance, in large part, due to their considerable compositional and structural flexibility. However, the formation of perovskites with neutr...

We show the improvement to cosmological constraints from galaxy cluster surveys with the addition of CMB-cluster lensing data. We explore the cosmological implications of adding mass information from the 3.1$\sigma$ detection of gravitational lensing of the cosmic microwave background (CMB) by galaxy clusters to the Sunyaev-Zel'dovich (SZ) selected galaxy cluster sample from the 2500 deg$^2$ SPT-SZ survey and targeted optical and X-ray followup data. In the $\Lambda$CDM model, the combination of the cluster sample with the Planck power spectrum measurements prefers $\sigma_8 \left(\Omega_m/0.3 \right)^{0.5} = 0.831 \pm 0.020$. Adding the cluster data reduces the uncertainty on this quantity by a factor of 1.4, which is unchanged whether or not the 3.1$\sigma$ CMB-cluster lensing measurement is included. We then forecast the impact of CMB-cluster lensing measurements with future cluster catalogs. Adding CMB-cluster lensing measurements to the SZ cluster catalog of the on-going SPT-3G survey is expected to improve the expected constraint on the dark energy equation of state $w$ by a factor of 1.3 to $\sigma(w) = 0.19$. We find the largest improvements from CMB-cluster lensing measurements to be for $\sigma_8$, where adding CMB-cluster lensing data to the cluster number counts reduces the expected uncertainty on $\sigma_8$ by factors of 2.4 and 3.6 for SPT-3G and CMB-S4 respectively., Comment: Comments are welcome

Manipulation of enzyme behaviour represents a sustainable technology that can be harnessed to enhance the production of valuable metabolites and chemical precursors. β-Glucose 1,6-bisphosphate (βG16BP) is a native reaction intermediate in the catalytic cycle of β-phosphoglucomutase (βPGM) that has been proposed as a treatment for human congenital disorder of glycosylation involving phosphomannomutase 2. Strategies to date for the synthesis of βG16BP suffer from low yields or use chemicals and procedures with significant environmental impacts. Herein, we report the efficient enzymatic synthesis of anomer-specific βG16BP using the D170N variant of βPGM (βPGMD170N), where the aspartate to asparagine substitution at residue 170 perturbs the coordination of a catalytic magnesium ion. Through combined use of NMR spectroscopy and kinetic assays, it is shown that the weakened affinity and reactivity of βPGMD170N towards βG16BP contributes to the pronounced retardation of the second step in the two-step catalytic cycle, which causes a marked accumulation of βG16BP, especially at elevated MgCl2 concentrations. Purification, employing a simple environmentally considerate precipitation procedure requiring only a standard biochemical toolset, results in a βG16BP product with high purity and yield. Overall, this synthesis strategy illustrates how manipulation of the catalytic magnesium coordination of an enzyme can be utilised to generate large quantities of a valuable metabolite.

Measurements of the Hubble constant, $H_0$, from the cosmic distance ladder are currently in tension with the value inferred from Planck observations of the CMB and other high redshift datasets if a flat $\Lambda$CDM cosmological model is assumed. One of the few promising theoretical resolutions of this tension is to invoke new physics that changes the sound horizon scale in the early universe; this can bring CMB and BAO constraints on $H_0$ into better agreement with local measurements. In this paper, we discuss how a measurement of the Hubble constant can be made from the CMB without using information from the sound horizon scale, $r_s$. In particular, we show how measurements of the CMB lensing power spectrum can be used to place interesting constraints on $H_0$ when combined with measurements of either supernovae or galaxy weak lensing, which constrain the matter density parameter. The constraints arise from the sensitivity of the CMB lensing power spectrum to the horizon scale at matter-radiation equality (in projection); this scale could have a different dependence on new physics than the sound horizon. From an analysis of current CMB lensing data from Planck and Pantheon supernovae with conservative external priors, we derive an $r_s$-independent constraint of $H_0 = 73.5\pm 5.3$ km/s/Mpc. Forecasts for future CMB surveys indicate that improving constraints beyond an error of $\sigma(H_0) = 3$ km/s/Mpc will be difficult with CMB lensing, although applying similar methods to the galaxy power spectrum may allow for further improvements., Comment: 14 pages, 6 figures; minor revision to match version accepted by MNRAS

To describe current bowel management program (BMP) strategies in anorectal malformation (ARM) patients based on patient-level predictors using data from a multi-institutional consortium.Patient bowel function and BMP were reviewed from Pediatric Colorectal and Pelvic Learning Consortium (PCPLC) data. The PCPLC is comprised of multidisciplinary specialists researching colorectal and pelvic disorders. Seven US institutions submitted de-identified clinical data on ARM patients into a centralized patient registry.The primary ARM of 624 patients was categorized into Mild (45.2%), Moderate (40.4%) or Complex (14.2%) anomaly classifications. Patient-specific BMP were examined based on age and on the presence of spinal cord/sacral anomalies. 418 (67%) enrolled patients were prescribed BMP (5 yo 56.4%; ≥5-12 yo 86.7%; ≥12 81.5%). Constipation was the primary chief complaint (80.2%). Forty percent of patients on a BMP were toilet trained and approximately one-half (48.5%) reported daytime stool accidents. Secondary surgical interventions for antegrade continence enemas (ACE) were examined; 14.5% of patients employed ACE strategies and utilization increased with age and varied based on anatomic anomalies.This is the first report on BMP strategies for patients with ARM from the Pediatric Colorectal and Pelvic Learning Consortium. Individual patient characteristics are explored for their impact on bowel management strategy utilization.IV.

Mapping suitable habitat is an important process in wildlife conservation planning. Species distribution reflects habitat selection processes occurring across multiple spatio‐temporal scales. Because habitat selection may be driven by different factors at different scales, conservation planners require information at the scale of the intervention to plan effective management actions. Previous research has described habitat selection processes shaping the distribution of greater sage‐grouse (Centrocercus urophasianus; sage‐grouse) at the range‐wide scale. Finer‐scale information for applications within jurisdictional units inside the species range is lacking, yet necessary, because state wildlife agencies are the management authority for sage‐grouse in the United States. We quantified seasonal second‐order habitat selection for sage‐grouse across the state of Utah to produce spatio‐temporal predictions of their distribution at the southern periphery of the species range. We used location data obtained from sage‐grouse marked with very‐high‐frequency radio‐transmitters and lek location data collected between 1998 and 2013 to quantify species habitat selection in relation to a suite of topographic, edaphic, climatic, and anthropogenic variables using random forest algorithms. Sage‐grouse selected for greater sagebrush (Artemisia spp.) cover, higher elevations, and gentler slopes and avoided lower precipitations and higher temperatures. The strength of responses to habitat variables varied across seasons. Anthropogenic variables previously reported as affecting their range‐wide distribution (i.e., roads, powerlines, communication towers, and agricultural development) were not ranked as top predictors at our focal scale. Other than strong selection for sagebrush cover, the responses we observed differed from what has been reported at the range‐wide scale. These differences likely reflect the unique climatic, geographic, and topographic context found in the southern peripheral area of the species distribution compared to range‐wide environmental gradients. Our results highlight the importance of considering appropriateness of scale when planning conservation actions for wide‐ranging species., We used random forest algorithms to map seasonal habitat selection for greater sage‐grouse at the southern periphery of their range. Results will provide scale‐appropriate information for management decisions at the state jurisdiction level in Utah.

Density measurements suggest that the incorporation of ZrF4 into the cubic ReO3-type structure of Sc1–xZrxF3+x is associated with the creation of anion interstitials. X-ray total scattering measure...

Background Adults with traumatic brain injury (TBI) who present hypertensive suffer worse outcomes and increased mortality compared to normotensive patients. The purpose of this study is to determine if age-adjusted hypertension on presentation is associated with worsened outcomes in pediatric TBI. Methods A retrospective chart review was conducted on pediatric patients with severe TBI admitted to a single system pediatric tertiary care center. The primary outcome was mortality. Secondary outcomes included length of stay, need for neurosurgical intervention, duration of mechanical ventilation, and the need for inpatient rehabilitation. Results Of 150 patients, 70% were hypertensive and 30% were normotensive on presentation. Comparing both groups, no statistically significant differences were noted in mortality (13.3% for both groups), need for neurosurgical intervention (51.4% vs 48.8%, p = 0.776), length of stay (6 vs 8 days, p = 0.732), duration of mechanical ventilation (2 vs 3 days, p = 0.912), or inpatient rehabilitation rates (48.6% vs 48.9%, p = 0.972). In comparing just the hypertensive patients, there was a trend toward increased mortality in the 95th and 99th percentile groups at 15.8% and 14.1%, versus the 90th percentile group at 6.7% but the difference was not statistically significant (p = 0.701). Conclusions Contrary to the adult literature, pediatric patients with severe TBI and hypertension on presentation do not appear to have worsened outcomes compared to those who are normotensive. However, a trend toward increased mortality did exist at extremes of age adjusted hypertension. Larger scale studies are needed to validate these findings. Study type Retrospective cohort study Level of Evidence III

IntroductionThe UK social security system is being transformed by the implementation of Universal Credit (UC), which combines six existing benefits and tax credits into a single payment for low-income households. Despite extensive reports of hardship associated with the introduction of UC, no previous studies have comprehensively evaluated its impact on mental health. Because payments are targeted at low-income households, impacts on mental health will have important consequences for health inequalities.Methods and analysisWe will conduct a mixed methods study. Work package (WP) 1 will compare health outcomes for new recipients of UC with outcomes for legacy benefit recipients in two large population surveys, using the phased rollout of UC as a natural experiment. We will also analyse the relationship between the proportion of UC claimants in small areas and a composite measure of mental health. WP2 will use data collected by Citizen’s Advice to explore the sociodemographic and health characteristics of people who seek advice when claiming UC and identify features of the claim process that prompt advice-seeking. WP3 will conduct longitudinal in-depth interviews with up to 80 UC claimants in England and Scotland to explore reasons for claiming and experiences of the claim process. Up to 30 staff supporting claimants will also be interviewed. WP4 will use a dynamic microsimulation model to simulate the long-term health impacts of different implementation scenarios. WP5 will undertake cost–consequence analysis of the potential costs and outcomes of introducing UC and cost–benefit analyses of mitigating actions.Ethics and disseminationWe obtained ethical approval for the primary data gathering from the University of Glasgow, College of Social Sciences Research Ethics Committee, application number 400200244. We will use our networks to actively disseminate findings to UC claimants, the public, practitioners and policy-makers, using a range of methods and formats.Trial registration numberThe study is registered with the Research Registry: researchregistry6697.

We consider the effect of a nonvanishing fraction of initially infected nodes (seeds) on the susceptible-infected-recovered epidemic model on random networks. This is relevant when the number of arriving infected individuals is large, or to the spread of ideas with publicity campaigns. This model is frequently studied by mapping to a bond percolation problem, in which edges are occupied with the probability p of eventual infection along an edge. This gives accurate measures of the final size of the infection and epidemic threshold in the limit of a vanishingly small seed fraction. We show, however, that when the initial infection occupies a nonvanishing fraction, f, of the network, this method yields ambiguous results, as the correspondence between edge occupation and contagion transmission no longer holds. We propose instead to measure the giant component of recovered individuals within the original contact network. We derive exact equations for the size of the epidemic and the epidemic threshold in the infinite size limit in heterogeneous sparse random networks, and we confirm them with numerical results. We observe that the epidemic threshold correctly depends on f, decreasing as f increases. When the seed fraction tends to zero, we recover the standard results.

The COVID-19 pandemic has taken a devastating human toll worldwide. The development of impactful guidelines and measures for controlling the COVID-19 pandemic requires continuous and widespread testing of suspected cases and their contacts through accurate, accessible, and reliable methods for SARS-CoV-2 detection. Here we describe a CRISPR-Cas13-based method for the detection of SARS-CoV-2. The assay is called CREST (Cas13-based, rugged, equitable, scalable testing), and is specific, sensitive, and highly accessible. As such, CREST may provide a low-cost and dependable alternative for SARS-CoV-2 surveillance. © 2022 Wiley Periodicals LLC. Basic Protocol: Cas13-ased detection of SARS-CoV-2 genetic material using a real-time PCR detection system Alternate Protocol: Cas13-based detection of SARS-CoV-2 genetic material using a fluorescence viewer Support Protocol 1: LwaCas13a purification Support Protocol 2: In vitro transcription of synthetic targets.

ObjectivesTo assess sexual behaviour, and sexual and reproductive health (SRH) outcomes, after 1 year of the COVID-19 pandemic in Britain.Methods6658 participants aged 18–59 and resident in Britain completed a cross-sectional web-panel survey (Natsal-COVID-Wave 2, March-April 2021), 1 year after the first lockdown. Natsal-COVID-2 follows the Natsal-COVID-Wave 1 survey (July-August 2020) which captured impacts in the initial months. Quota-based sampling and weighting resulted in a quasi-representative population sample. Data were contextualised with reference to the most recent probability sample population data (Natsal-3; collected 2010–12; 15 162 participants aged 16–74) and national surveillance data on recorded sexually transmitted infection (STI) testing, conceptions, and abortions in England/Wales (2010–2020). The main outcomes were: sexual behaviour; SRH service use; pregnancy, abortion and fertility management; sexual dissatisfaction, distress and difficulties.ResultsIn the year from the first lockdown, over two-thirds of participants reported one or more sexual partners (women 71.8%; men 69.9%), while fewer than 20.0% reported a new partner (women 10.4%; men 16.8%). Median occasions of sex per month was two. Compared with 2010–12 (Natsal-3), we found less sexual risk behaviour (lower reporting of multiple partners, new partners, and new condomless partners), including among younger participants and those reporting same-sex behaviour. One in 10 women reported a pregnancy; pregnancies were fewer than in 2010–12 and less likely to be scored as unplanned. 19.3% of women and 22.8% of men were distressed or worried about their sex life, significantly more than in 2010–12. Compared with surveillance trends from 2010 to 2019, we found lower than expected use of STI-related services and HIV testing, lower levels of chlamydia testing, and fewer conceptions and abortions.ConclusionsOur findings are consistent with significant changes in sexual behaviour, SRH, and service uptake in the year following the first lockdown in Britain. These data are foundational to SRH recovery and policy planning.

There are several approaches for the simulation of nonlinear nanophotonic devices such as the nonlinear polarization method, the hydrodynamic model, and the non-linear scattering theory. We compare and discuss these techniques for plasmonic structures using the finite-difference time-domain (FDTD) method.