Structural basis of coactivation of liver receptor homolog-1 by β-catenin

We report the three-dimensional structure of a β-catenin armadillo repeat in complex with the liver receptor homolog-1 (LRH-1) ligand binding domain at 2.8 Å resolution as the first structure of β-catenin in complex with any nuclear receptor. The surface of β-catenin that binds LRH-1 partly overlaps defined contact sites for peptide segments of β-catenin partners, including T-cell factor-4. The surface of LRH-1 that engages β-catenin is comprised of helices 1, 9, and 10 and is distinct from known interaction surfaces of LRH-1, including corepressor and coactivator binding sites. Targeted mutagenesis of amino acids forming both sides of the LRH-1/β-catenin interface reveals that they are essential for stable interactions between these proteins in solution. The LRH-1 binding site in β-catenin is also required for association with androgen receptor, providing evidence that the observed LRH-1/β-catenin interaction may be prototypic.     

Protected areas facilitate species' range expansions

The benefits of protected areas (PAs) for biodiversity have been questioned in the context of climate change because PAs are static, whereas the distributions of species are dynamic. Current PAs may, however, continue to be important if they provide suitable locations for species to colonize at their leading-edge range boundaries, thereby enabling spread into new regions. Here, we present an empirical assessment of the role of PAs as targets for colonization during recent range expansions. Records from intensive surveys revealed that seven bird and butterfly species have colonized PAs 4.2 (median) times more frequently than expected from the availability of PAs in the landscapes colonized. Records of an additional 256 invertebrate species with less-intensive surveys supported these findings and showed that 98% of species are disproportionately associated with PAs in newly colonized parts of their ranges. Although colonizing species favor PAs in general, species vary greatly in their reliance on PAs, reflecting differences in the dependence of individual species on particular habitats and other conditions that are available only in PAs. These findings highlight the importance of current PAs for facilitating range expansions and show that a small subset of the landscape receives a high proportion of colonizations by range-expanding species.     

The contribution of major depression to the global burden of ischemic heart disease: a comparative risk assessment

Background

Cardiovascular disease and mental health both hold enormous public health importance, both ranking highly in results of the recent Global Burden of Disease Study 2010 (GBD 2010). For the first time, the GBD 2010 has systematically and quantitatively assessed major depression as an independent risk factor for the development of ischemic heart disease (IHD) using comparative risk assessment methodology.

Methods

A pooled relative risk (RR) was calculated from studies identified through a systematic review with strict inclusion criteria designed to provide evidence of independent risk factor status. Accepted case definitions of depression include diagnosis by a clinician or by non-clinician raters adhering to Diagnostic and Statistical Manual of Mental Disorders (DSM) or International Classification of Diseases (ICD) classifications. We therefore refer to the exposure in this paper as major depression as opposed to the DSM-IV category of major depressive disorder (MDD). The population attributable fraction (PAF) was calculated using the pooled RR estimate. Attributable burden was calculated by multiplying the PAF by the underlying burden of IHD estimated as part of GBD 2010.

Results

The pooled relative risk of developing IHD in those with major depression was 1.56 (95% CI 1.30 to 1.87). Globally there were almost 4 million estimated IHD disability-adjusted life years (DALYs), which can be attributed to major depression in 2010; 3.5 million years of life lost and 250,000 years of life lived with a disability. These findings highlight a previously underestimated mortality component of the burden of major depression. As a proportion of overall IHD burden, 2.95% (95% CI 1.48 to 4.46%) of IHD DALYs were estimated to be attributable to MDD in 2010. Eastern Europe and North Africa/Middle East demonstrate the highest proportion with Asia Pacific, high income representing the lowest.

Conclusions

The present work comprises the most robust systematic review of its kind to date. The key finding that major depression may be responsible for approximately 3% of global IHD DALYs warrants assessment for depression in patients at high risk of developing IHD or at risk of a repeat IHD event.

     

Factors influencing adherence to antiretroviral treatment in Asian developing countries: a systematic review

Objective To systematically review the literature of factors affecting adherence to Antiretroviral treatment (ART) in Asian developing countries. Methods Database searches in Medline/Ovid, Cochrane library, CINAHL, Scopus and PsychINFO for studies published between 1996 and December 2010. The reference lists of included papers were also checked, with citation searching on key papers. Results A total of 437 studies were identified, and 18 articles met the inclusion criteria and were extracted and critically appraised, representing in 12 quantitative, four qualitative and two mixed‐method studies. Twenty‐two individual themes, including financial difficulties, side effects, access, stigma and discrimination, simply forgetting and being too busy, impeded adherence to ART, and 11 themes, including family support, self‐efficacy and desire to live longer, facilitated adherence. Conclusion Adherence to ART varies between individuals and over time. We need to redress impeding factors while promoting factors that reinforce adherence through financial support, better accessible points for medicine refills, consulting doctors for help with side effects, social support and trusting relationships with care providers.     

Functionalism and holism: community nurses' perceptions of health

This paper reports the results of a study that was designed to explore and examine the perceptions of two groups of newly qualified community nurses about the factors they considered to be embedded within the concepts of health, health-enhancing behaviours at individual, family and community levels and their 'innermost self'. The research was exploratory in nature, and included two sample groups: group 1 comprised 16 newly qualified health visitors; group 2 comprised 16 newly qualified community mental health nurses. Purposive sampling was used and data were collected using semi-structured interviews. The group of health visitors perceived health in terms of physical fitness and functional states. At a global level they perceived the need to provide education on health matters. They gave generously to 'charities' and perceived the 'inner self' as 'that part that matters'. The group of community mental health nurses perceived health in terms of holism and being states. Their concept of health was related to listening to each individual's perception of what is 'right' and 'health-enhancing' for them. At a global level they considered the protection of the ozone layer and the promotion of a just and equitable society which focused on the reduction of poverty, to be key health-enhancing activities. They perceived their 'innermost self' to be 'that part of me that makes life worth living', and the soul. The findings have implications for developing new and creative approaches for teaching the holistic concept of health and healing. Educational activities could be designed which strive to ensure that nurses themselves have safe and health embracing opportunities for exploring all the elements that are embedded within the topic of health. Their role in facilitating holistic health promoting activities for all clients also needs to be addressed.