The structure of the complex between the arsenite oxidase from Pseudorhizobium banfieldiae sp. strain NT-26 and its native electron acceptor cytochrome c552

The arsenite oxidase (AioAB) from Pseudorhizobium banfieldiae sp. strain NT-26 catalyzes the oxidation of arsenite to arsenate and transfers electrons to its cognate electron acceptor cytochrome c552 (cytc552). This activity underpins the ability of this organism to respire using arsenite present in contaminated environments. The crystal structure of the AioAB/cytc552 electron transfer complex reveals two A2B2/(cytc552)2 assemblies per asymmetric unit. Three of the four cytc552 molecules in the asymmetric unit dock to AioAB in a cleft at the interface between the AioA and AioB subunits, with an edge-to-edge distance of 7.5 Å between the heme of cytc552 and the [2Fe–2S] Rieske cluster in the AioB subunit. The interface between the AioAB and cytc552 proteins features electrostatic and nonpolar interactions and is stabilized by two salt bridges. A modest number of hydrogen bonds, salt bridges and relatively small, buried surface areas between protein partners are typical features of transient electron transfer complexes. Interestingly, the fourth cytc552 molecule is positioned differently between two AioAB heterodimers, with distances between its heme and the AioAB redox active cofactors that are outside the acceptable range for fast electron transfer. This unique cytc552 molecule appears to be positioned to facilitate crystal packing rather than reflecting a functional complex

Work-life imbalance: informal care and paid employment

In the United Kingdom informal carers are people who look after relatives or friends who need extra support because of age, physical or learning disability or illness. The majority of informal carers are women and female carers also care for longer hours and for longer durations than men. Thus women and older women in particular, shoulder the burden of informal care. We consider the costs of caring in terms of the impact that these kinds of caring responsibilities have on employment. The research is based on the responses of informal carers to a dedicated questionnaire and in-depth interviews with a smaller sub-sample of carers. Our results indicate that the duration of a caring episode as well as the hours carers commit to caring impact on their employment participation. In addition carers’ employment is affected by financial considerations, the needs of the person they care for, carers’ beliefs about the compatibility of informal care and paid work and employers’ willingness to accommodate carers’ needs. Overall, the research confirms that informal carers continue to face difficulties when they try to combine employment and care in spite of recent policy initiatives designed to help them

Exclusion, inclusion and belonging in mainstream and disability sport: Jack’s story

Concepts of exclusion and inclusion in sport, physical activity and physical education settings are mostly anchored to discussions about access to and opportunities in physical and social spaces from the perspective of non-disabled adult stakeholders. In this article, we use individual interviews and two creative non-fiction accounts to explore the views of an adult with cerebral palsy (CP), named Jack, who reflects on his embodied experiences of mainstream and CP youth football. This approach enabled us to provide a more nuanced and sophisticated consideration of the exclusion/inclusion dichotomy by centring Jack’s construction of identity and feelings of belonging in the spaces his body inhabited. Particular attention is paid to the interactions and relationships that Jack developed with teammates and coaches, and the (often ableist) constructs of ability that pervade mainstream and CP settings, all of which served to influence Jack’s sense of belonging. We end by encouraging scholars to centre the experiences and amplify the voices of disabled young people, and to consider inclusion as intersubjective experiences associated with feelings of belonging, acceptance and value that are dynamic and in flux. The concept of embodied belonging can help us to move researchers beyond a simple critique of disabling socio-spatial power relations towards the construction of new knowledge that enhances understandings of disability, place, and space

Indoor Particulate Air Pollution from Open Fires and the Cognitive Function of Older People

Exposure to indoor air pollution is known to affect respiratory and cardiovascular health, but little is known about its effects on cognitive function. We measured the concentrations and magnetite content of airborne particulate matter (PM) in the indoor environment arising from burning peat, wood or coal in residential open fires. Highest indoor PM2.5 concentrations (60 µg/m3, i.e. 2.4 times the WHO-recommended 24-hour mean) occurred when peat was burned, followed by burning of coal (30 µg/m3) and wood (17 µg/m3). Conversely, highest concentrations of coarser PM (PM10-2.5) were associated with coal burning (20 µg/m3), with lower concentrations emitted during burning of wood (10 µg/m3) and peat (8 µg/m3). The magnetic content of the emitted PM, greatest (for both PM size fractions) when coal was burned, is similar to that of roadside airborne PM. Exposure to PM, and to strongly magnetic airborne PM, can be greater for individuals spending ~5 hours/day indoors with a coal-burning open fire for 6 months/year compared to those commuting via heavily-trafficked roads for 1 hour/day for 12 months/year. Given these high indoor PM and magnetite concentrations, and the reported associations between (outdoor) PM and impaired neurological health, we used individual-level data from The Irish Longitudinal Study on Ageing (TILDA) to examine the association between the usage of open fires and the cognitive function of older people. Using a sample of nearly seven thousand older people, we estimated multi-variate models of the association between cognitive function and open fire usage, in order to account for relevant confounders such as socio-economic status. We found a negative association between open fire usage and cognitive function as measured by widely-used cognitive tests such as word recall and verbal fluency tests. The negative association was largest and statistically strongest among women, a finding explained by the greater exposure of women to open fires in the home because they spent more time at home than men. Our findings were also robust to stratifying the sample between old and young, rich and poor, and urban and rural

Identifying a Novel Role for Fractalkine (CX3CL1) in Memory CD8(+) T Cell Accumulation in the Omentum of Obesity-Associated Cancer Patients

The omentum is enriched with pro-inflammatory effector memory CD8+ T cells in patients with the obesity-associated malignancy, esophagogastric adenocarcinoma (EAC) and we have identified the chemokine macrophage inflammatory protein-1alpha as a key player in their active migration to this inflamed tissue. More recently, others have established that subsets of memory CD8+ T cells can be classified based on their surface expression of CX3CR1; the specific receptor for the inflammatory chemokine fractalkine. CD8+ T cells expressing intermediate levels (CX3CR1INT) are defined as peripheral memory, those expressing the highest levels (CX3CR1HI) are effector memory/terminally differentiated and those lacking CX3CR1 (CX3CR1NEG) are classified as central memory. To date, the fractalkine:CX3CR1 axis has not been examined in the context of CD8+ T cell enrichment in the omentum and here we examine this chemokines involvement in the accumulation of memory CD8+ T cells in the omentum of EAC patients. Our data show that fractalkine is significantly enriched in the omentum of EAC patients and drives migration of T cells derived from EAC patient blood. Furthermore, CX3CR1 is endocytosed specifically by CD8+ T cells upon encountering fractalkine, which is consistent with the significantly diminished frequencies of CX3CR1INT and CX3CR1HI CD8+ T cells in the fractalkine-rich environment of omentum in EAC, relative to matched blood. Fractalkine-mediated endocytosis of CX3CR1 by CD8+ T cells is sustained and is followed by enhanced surface expression of L-selectin (CD62L). These novel data align with our findings that circulating CX3CR1NEG CD8+ T cells express higher levels of L-selectin than CX3CR1INT CD8+ T cells. This is consistent with previous reports and implicates fractalkine in the conversion of CX3CR1INT CD8+ T cells to a CX3CR1NEG phenotype characterized by alterations in the migratory capacity of these T cells. For the first time, these findings identify fractalkine as a driver of T cell migration to the omentum in EAC and indicate that CD8+ T cells undergo sequenced fractalkine-mediated alterations in CX3CR1 and L-selectin expression. These data implicate fractalkine as more than a chemotactic cytokine in obesity-associated meta-inflammation and reveal a role for this chemokine in the maintenance of the CX3CR1NEG CD8+ T cell populations

Molecular Phylogeny of Edge Hill Virus Supports its Position in the Yellow Fever Virus Group and Identifies a New Genetic Variant

Edge Hill virus (EHV) is a mosquito-borne flavivirus isolated throughout Australia during mosquito surveillance programs. While not posing an immediate threat to the human population, EHV is a taxonomically interesting flavivirus since it remains the only member of the yellow fever virus (YFV) sub-group to be detected within Australia. Here we present both an antigenic and genetic investigation of collected isolates, and confirm taxonomic classification of the virus within the YFV-group. Isolates were not clustered based on geographical origin or time of isolation, suggesting that minimal genetic evolution of EHV has occurred over geographic distance or time within the EHV cluster. However, two isolates showed significant differences in antigenic reactivity patterns, and had a much larger divergence from the EHV prototype (19% nucleotide and 6% amino acid divergence), indicating a distinct subtype or variant within the EHV subgroup

SDHC epi-mutation testing in gastrointestinal stromal tumours and related tumours in clinical practice

Abstract: The enzyme succinate dehydrogenase (SDH) functions in the citric acid cycle and loss of function predisposes to the development of phaeochromocytoma/paraganglioma (PPGL), wild type gastrointestinal stromal tumour (wtGIST) and renal cell carcinoma. SDH-deficient tumours are most commonly associated with a germline SDH subunit gene (SDHA/B/C/D) mutation but can also be associated with epigenetic silencing of the SDHC gene. However, clinical diagnostic testing for an SDHC epimutation is not widely available. The objective of this study was to investigate the indications for and the optimum diagnostic pathways for the detection of SDHC epimutations in clinical practice. SDHC promoter methylation analysis of 32 paraffin embedded tumours (including 15 GIST and 17 PPGL) was performed using a pyrosequencing technique and correlated with SDHC gene expression. SDHC promoter methylation was identified in 6 (18.7%) tumours. All 6 SDHC epimutation cases presented with SDH deficient wtGIST and 3/6 cases had multiple primary tumours. No case of constitutional SDHC promoter hypermethylation was detected. Whole genome sequencing of germline DNA from three wtGIST cases with an SDHC epimutation, did not reveal any causative sequence anomalies. Herein, we recommend a diagnostic workflow for the detection of an SDHC epimutation in a service setting

Trends in prolonged sitting time among European adults: 27 country analysis

OBJECTIVE: To examine trends in adult sitting time across 27 European countries.  METHOD: Data were from the Eurobarometer surveys collected in 2002, 2005, and 2013. Sitting time data were used to categorise respondents into 'low' (0 to 4h30min), 'middle' (4h31min to 7h30min), and 'high' levels of sitting (>7h30min). We modelled the likelihood of being in the high sitting group within a given country and overall across the three time points, controlling for age, gender, education, employment status, and physical activity.  RESULTS: In total 17 countries had sitting data at all three time points; among these countries the prevalence of 'high sitting' decreased steadily from 23.1% (95% CI=22.2-24.1) in 2002 to 21.8% (95% CI=20.8-22.8) in 2005, and 17.8% (95% CI=16.9-18.7) in 2013. A further 10 countries had data only over the latter two time points; among these countries the prevalence of high sitting decreased from 27.7% (95% CI=26.0-29.4) in 2005 to 19.0% (95% CI=17.6-20.5) in 2013.  CONCLUSION: Time spent in sedentary behaviour may not be increasing in the European region, and prolonged sitting may, in fact, be decreasing. This finding has important implications for the sedentary behaviour debate and the policy response

Factors associated with financial security, food security and quality of daily lives of residents in Nigeria during the first wave of the COVID-19 pandemic

An online survey was conducted to identify factors associated with financial insecurity, food insecurity and poor quality of daily lives of adults in Nigeria during the first wave of the COVID-19 pandemic. The associations between the outcome (experience of financial loss, changes in food intake and impact of the pandemic on daily lives) and the explanatory (age, sex, education level, anxiety, depression, HIV status) variables were determined using logistic regression analysis. Of the 4439 respondents, 2487 (56.0%) were financially insecure, 907 (20.4%) decreased food intake and 4029 (90.8%) had their daily life negatively impacted. Males (AOR:0.84), people who felt depressed (AOR:0.62) and people living with HIV -PLHIV- (AOR:0.70) had significantly lower odds of financial insecurity. Older respondents (AOR:1.01) had significantly higher odds of financial insecurity. Those depressed (AOR:0.62) and PLHIV (AOR:0.55) had significantly lower odds of reporting decreased food intake. Respondents who felt anxious (AOR:0.07), depressed (AOR: 0.48) and who were PLHIV (AOR:0.68) had significantly lower odds of reporting a negative impact of the pandemic on their daily lives. We concluded the study findings may reflect a complex relationship between financial insecurity, food insecurity, poor quality of life, mental health, and socioeconomic status of adults living in Nigeria during the COVID-19 pandemic

Level of agreement between frequently used cardiovascular risk calculators in people living with HIV

Objectives The aim of the study was to describe agreement between the QRISK2, Framingham and Data Collection on Adverse Events of Anti‐HIV Drugs (D:A:D) cardiovascular disease (CVD) risk calculators in a large UK study of people living with HIV (PLWH). Methods PLWH enrolled in the Pharmacokinetic and Clinical Observations in People over Fifty (POPPY) study without a prior CVD event were included in this study. QRISK2, Framingham CVD and the full and reduced D:A:D CVD scores were calculated; participants were stratified into ‘low’ ( 20%) categories for each. Agreement between scores was assessed using weighted kappas and Bland–Altman plots. Results The 730 included participants were predominantly male (636; 87.1%) and of white ethnicity (645; 88.5%), with a median age of 53 [interquartile range (IQR) 49–59] years. The median calculated 10‐year CVD risk was 11.9% (IQR 6.8–18.4%), 8.9% (IQR 4.6–15.0%), 8.5% (IQR 4.8–14.6%) and 6.9% (IQR 4.1–11.1%) when using the Framingham, QRISK2, and full and reduced D:A:D scores, respectively. Agreement between the different scores was generally moderate, with the highest level of agreement being between the Framingham and QRISK2 scores (weighted kappa = 0.65) but with most other kappa coefficients in the 0.50–0.60 range. Conclusions Estimates of predicted 10‐year CVD risk obtained with commonly used CVD risk prediction tools demonstrate, in general, only moderate agreement among PLWH in the UK. While further validation with clinical endpoints is required, our findings suggest that care should be taken when interpreting any score alone