Structural diversity in the RGS domain and its interaction with heterotrimeric G protein alpha-subunits.

Regulator of G protein signaling (RGS) proteins accelerate GTP hydrolysis by Galpha subunits and thus facilitate termination of signaling initiated by G protein-coupled receptors (GPCRs). RGS proteins hold great promise as disease intervention points, given their signature role as negative regulators of GPCRs-receptors to which the largest fraction of approved medications are currently directed. RGS proteins share a hallmark RGS domain that interacts most avidly with Galpha when in its transition state for GTP hydrolysis; by binding and stabilizing switch regions I and II of Galpha, RGS domain binding consequently accelerates Galpha-mediated GTP hydrolysis. The human genome encodes more than three dozen RGS domain-containing proteins with varied Galpha substrate specificities. To facilitate their exploitation as drug-discovery targets, we have taken a systematic structural biology approach toward cataloging the structural diversity present among RGS domains and identifying molecular determinants of their differential Galpha selectivities. Here, we determined 14 structures derived from NMR and x-ray crystallography of members of the R4, R7, R12, and RZ subfamilies of RGS proteins, including 10 uncomplexed RGS domains and 4 RGS domain/Galpha complexes. Heterogeneity observed in the structural architecture of the RGS domain, as well as in engagement of switch III and the all-helical domain of the Galpha substrate, suggests that unique structural determinants specific to particular RGS protein/Galpha pairings exist and could be used to achieve selective inhibition by small molecules.

"A Lot of People Are Struggling Privately. They Don't Know Where to Go or They're Not Sure of What to Do": Frontline Service Provider Perspectives of the Nature of Household Food Insecurity in Scotland.

This qualitative study explored frontline service providers' perceptions of the nature of food insecurity in Scotland in 2015 to inform national policy and the provision of locally-based support for 'at risk' groups. A country-wide in-depth interview study was undertaken with informants from 25 health, social care, and third sector organisations. The study investigated informants' perspectives associated with how food insecurity was manifesting itself locally, and what was happening at the local level in response to the existence of food insecurity. Data analysis revealed three key themes. First, the multiple faces and factors of food insecurity involving not only increased concern for previously recognised 'at risk of food insecurity' groups, but also similar concern held about newly food insecure groups including working families, young people and women. Secondly, respondents witnessed stoicism and struggle, but also resistance amongst some food insecure individuals to external offers of help. The final theme identified community participation yet pessimism associated with addressing current and future needs of food insecure groups. These findings have important implications for the design and delivery of health and social policy in Scotland and other countries facing similar challenges.

What can Secondary Data Tell Us about Household Food Insecurity in a High-Income Country Context?

In the absence of routinely collected household food insecurity data, this study investigated what could be determined about the nature and prevalence of household food insecurity in Scotland from secondary data. Secondary analysis of the Living Costs and Food Survey (2007⁻2012) was conducted to calculate weekly food expenditure and its ratio to equivalised income for households below average income (HBAI) and above average income (non-HBAI). Diet Quality Index (DQI) scores were calculated for this survey and the Scottish Health Survey (SHeS, 2008 and 2012). Secondary data provided a partial picture of food insecurity prevalence in Scotland, and a limited picture of differences in diet quality. In 2012, HBAI spent significantly less in absolute terms per week on food and non-alcoholic drinks (£53.85) compared to non-HBAI (£86.73), but proportionately more of their income (29% and 15% respectively). Poorer households were less likely to achieve recommended fruit and vegetable intakes than were more affluent households. The mean DQI score (SHeS data) of HBAI fell between 2008 and 2012, and was significantly lower than the mean score for non-HBAI in 2012. Secondary data are insufficient to generate the robust and comprehensive picture needed to monitor the incidence and prevalence of food insecurity in Scotland.

A systematic review of population and community dietary interventions to prevent cancer.

Diet is an important factor in the causation of cancer. Previous systematic reviews of one-to-one interventions to encourage dietary change have found that such interventions can achieve modest improvements in diet. However, such interventions are resource intensive and unlikely to be good value for money at a population level. Interventions that address groups, communities or whole populations may be less resource intensive and effect change in a wider population. We report a systematic review of such interventions. We set wide inclusion criteria, including before-and-after studies and studies with a non-randomized comparison group as well as randomized trials. We found eighteen studies based in the community, seventeen based on worksites, five based in churches and one based in a supermarket. Interventions which targeted fruit and vegetable intake were most likely to be successful, particularly in worksites and churches. There was also evidence of small positive effects on reducing fat intake in worksites and churches. Overall the community-based interventions showed little effect. The studies included in the present review were generally poorly reported. Dietary changes are reported in the relatively short-term studies reviewed here but may not be sustained in the long term. The effects that we have identified are small but the reach is potentially very wide, in some cases as wide as a whole country. The cost effectiveness of such strategies remains to be evaluated.

Rights-based approaches to addressing food poverty and food insecurity in Ireland and UK.

Food poverty is an important contributing factor to health inequalities in industrialised countries; it refers to the inability to acquire or eat an adequate quality or sufficient quantity of food in socially acceptable ways (or the uncertainty of being able to do so). Synonymous with household food insecurity, the issue needs to be located within a social justice framework. Recognising the clear interdependence between the right to food and the right to health, this paper explores how international human rights obligations could inform approaches to addressing food poverty and insecurity with specific reference to Ireland and the UK. Little attention has been paid to how countries should meet their obligations to respect, protect and fulfil the right to food in developed countries. The paper contributes by examining the social and policy circumstances which inhibit poor households from obtaining sufficient food to eat healthily, along with strategies and interventions from State and civil society actors in the two countries. In practice, problems and potential solutions have largely been directed towards the individual rather than at social determinants, particularly as research on environmental factors such as distance to shops has produced equivocal results. Other key structural aspects such as income sufficiency for food are broadly ignored by the State, and anti-poverty strategies are often implemented without monitoring for effects on food outcomes. Thus scant evidence exists for either Ireland or the UK meeting its rights to food obligations to date, in terms of roles and responsibilities in ensuring access to affordable, available and appropriate food for all.

Symposium on 'Intervention policies for deprived households' Policy initiatives to address low-income households' nutritional needs in the UK.

Members of low-income households in the UK are more likely to have patterns of food and nutrient intakes that are less inclined to lead to good health outcomes in the short and long term. Health inequalities, including the likelihood of child and adulthood obesity, have long been documented in the UK and show little sign of improving so far, despite 10 years of attention from a government that has committed itself to addressing them. Following the Acheson Inquiry into Inequalities in Health (1998) in England a number of initiatives to tackle inequalities in food and diet were established, both nationally and within the devolved nations of Scotland, Wales and Northern Ireland. Nevertheless, until recently, there has been no overall strategic policy addressing the food and nutritional needs of low-income households. The present paper reviews how the problems have been constructed and understood and how they have been addressed, briefly drawing on recent evaluations of food and nutrition policies in Scotland and Wales. The contemporary challenge is to frame cross-cutting policy initiatives that move beyond simple targeting and local actions, encompass a life-course approach and recognise both the diversity of households that fall into 'low-income' categories and the need for 'upstream' intervention.

Backbone and sidechain 1H, 13C and 15N resonance assignments of the Bright/ARID domain from the human JARID1C (SMCX) protein.

We have assigned 1H, 13C and 15N resonances of the Bright/ARID DNA-binding domain from the human JARID1C protein, a newly discovered histone demethylase belonging to the JmjC domain-containing protein family.

Backbone and sidechain 1H, 13C and 15N resonance assignments of the RGS domain from human RGS14.

We have assigned 1H, 13C and 15N resonances of the RGS domain from the human RGS14 protein, a multi-domain member of the RGS (Regulators of G-protein signalling) family of proteins, important in the down-regulation of specific G-protein signalling pathways.

The impact of a community-based food skills intervention on cooking confidence, food preparation methods and dietary choices - an exploratory trial.

OBJECTIVE: To evaluate the feasibility of undertaking a food skills intervention study in areas of social deprivation aimed at altering cooking confidence, food preparation methods and dietary choices. DESIGN: A standardised skills programme was implemented in community-based settings. Pre- (T1) and post-intervention (T2) and 6-month follow-up (T3) measures (7-day diaries and self-administered questionnaires) were undertaken in intervention and comparison groups. SETTING: Eight urban communities in Scotland. SUBJECTS: One hundred and thirteen adults living in areas of social deprivation. RESULTS: It was clear that many subjects led fragmented lives and found commitment to intervention classes problematic. Sixty-three subjects completed the final (T3) assessments. The response to each component varied due to inability to attend sessions, illness, study requirements, employment, moving out of the area, change in circumstances, loss of interest and loss of postal questionnaires. At baseline, reported consumption of fruit and vegetables was low (mean frequency 8.1 +/- 4.78 times per week). Fruit intake increased significantly (P < 0.05) between T1 and T2 in the intervention group (1.7 +/- 2.36 to 2.7 +/- 3.28 times per week) only. Between T1 and T3, there was a significant increase (P < 0.05) in intervention subjects who reported confidence in following a recipe (67-90%,). CONCLUSIONS: This exploratory trial shows that a food skills intervention is likely to have a small but positive effect on food choice and confidence in food preparation. A full-scale randomised controlled trial in this hard-to-reach group would require a range of flexible approaches rather than a fully defined intervention, and presents challenges for trial design.

Public understanding of food risks in four European countries: a qualitative study.

BACKGROUND: In the wake of the 'bovine spongiform encephalopathy (BSE) crisis' there was renewed interest in how those responsible for public health could take account of public views, both to 'democratize' policy making and to increase the likelihood of information about health risks resonating with public concerns. This study explored how members of the public in four European countries (Finland, Germany, Italy and the UK) understood food risks in general, and risks arising from BSE in particular. The aims were to identify the sources of knowledge used and trusted by the public and to explore how public views could be accessed for public health information policy. METHODS: Thirty-six focus group interviews were held using a common protocol across the four countries, including people from four life-cycle stages. RESULTS: The study demonstrated the utility of using focus groups as a relatively efficient method for accessing public views, and the feasibility of cross-national qualitative research on public views. We found that public views of food risks are neither irrational nor naïve, but that they do need to be interpreted in the context of everyday food purchasing decisions, in which particular food risks are unlikely to have the same salience as they do for experts. CONCLUSIONS: Focus groups are a feasible method for accessing public knowledge on public health risks to inform information strategies.