Integrated Analysis of Residue Coevolution and Protein Structure in ABC Transporters

Intraprotein side chain contacts can couple the evolutionary process of amino acid substitution at one position to that at another. This coupling, known as residue coevolution, may vary in strength. Conserved contacts thus not only define 3-dimensional protein structure, but also indicate which residue-residue interactions are crucial to a protein’s function. Therefore, prediction of strongly coevolving residue-pairs helps clarify molecular mechanisms underlying function. Previously, various coevolution detectors have been employed separately to predict these pairs purely from multiple sequence alignments, while disregarding available structural information. This study introduces an integrative framework that improves the accuracy of such predictions, relative to previous approaches, by combining multiple coevolution detectors and incorporating structural contact information. This framework is applied to the ABC-B and ABC-C transporter families, which include the drug exporter P-glycoprotein involved in multidrug resistance of cancer cells, as well as the CFTR chloride channel linked to cystic fibrosis disease. The predicted coevolving pairs are further analyzed based on conformational changes inferred from outward- and inward-facing transporter structures. The analysis suggests that some pairs coevolved to directly regulate conformational changes of the alternating-access transport mechanism, while others to stabilize rigid-body-like components of the protein structure. Moreover, some identified pairs correspond to residues previously implicated in cystic fibrosis

Absence of evidence for the conservation outcomes of systematic conservation planning around the globe : A systematic map

Background Systematic conservation planning is a discipline concerned with the prioritisation of resources for biodiversity conservation and is often used in the design or assessment of terrestrial and marine protected area networks. Despite being an evidence-based discipline, to date there has been no comprehensive review of the outcomes of systematic conservation plans and assessments of the relative effectiveness of applications in different contexts. To address this fundamental gap in knowledge, our primary research question was: what is the extent, distribution and robustness of evidence on conservation outcomes of systematic conservation planning around the globe? Methods A systematic mapping exercise was undertaken using standardised search terms across 29 sources, including publication databases, online repositories and a wide range of grey literature sources. The review team screened articles recursively, first by title only, then abstract and finally by full-text, using inclusion criteria related to systematic conservation plans conducted at sub-global scales and reported on since 1983. We sought studies that reported outcomes relating to natural, human, social, financial or institutional outcomes and which employed robust evaluation study designs. The following information was extracted from included studies: bibliographic details, background information including location of study and broad objectives of the plan, study design, reported outcomes and context. Results Of the approximately 10,000 unique articles returned through our searches, 1209 were included for full-text screening and 43 studies reported outcomes of conservation planning interventions. However, only three studies involved the use of evaluation study designs which are suitably rigorous for inclusion, according to best-practice guidelines. The three included studies were undertaken in the Gulf of California (Mexico), Réunion Island, and The Nature Conservancy’s landholdings across the USA. The studies varied widely in context, purpose and outcomes. Study designs were non-experimental or qualitative, and involved use of spatial landholdings over time, stakeholder surveys and modelling of alternative planning scenarios. Conclusion Rigorous evaluations of systematic conservation plans are currently not published in academic journals or made publicly available elsewhere. Despite frequent claims relating to positive implications and outcomes of these planning activities, we show that evaluations are probably rarely conducted. This finding does not imply systematic conservation planning is not effective but highlights a significant gap in our understanding of how, when and why it may or may not be effective. Our results also corroborate claims that the literature on systematic conservation planning is dominated by methodological studies, rather than those that focus on implementation and outcomes, and support the case that this is a problematic imbalance in the literature. We emphasise the need for academics and practitioners to publish the outcomes of systematic conservation planning exercises and to consider employing robust evaluation methodologies when reporting project outcomes. Adequate reporting of outcomes will in turn enable transparency and accountability between institutions and funding bodies as well as improving the science and practice of conservation planning

Economic Globalization, Nutrition and Health: a review of quantitative evidence

BACKGROUND: Unhealthy dietary patterns have in recent decades contributed to an endemic-level burden from non-communicable disease (NCDs) in high-income countries. In low- and middle-income countries rapid changes in diets are also increasingly linked to malnutrition in all its forms as persistent undernutrition and micronutrient deficiencies continue to coexist with a rising prevalence of obesity and associated NCDs. Economic globalization and trade liberalization have been identified as potentially important factors driving these trends, but the mechanisms, pathways and actual impact are subject to continued debate. METHODS: We use a ‘rigorous review’ to synthesize evidence from empirical quantitative studies analysing the links between economic globalization processes and nutritional outcomes, with a focus on impact as well as improving the understanding of the main underlying mechanisms and their interactions. FINDINGS: While the literature remains mixed regarding the impacts of overall globalization, trade liberalization or economic globalization on nutritional outcomes, it is possible to identify different patterns of association and impact across specific sub-components of globalization processes. Although results depend on the context and methods of analysis, foreign direct investment (FDI) appears to be more clearly associated with increases in overnutrition and NCD prevalence than to changes in undernutrition. Existing evidence does not clearly show associations between trade liberalization and NCD prevalence, but there is some evidence of a broad association with improved dietary quality and reductions in undernutrition. Socio-cultural aspects of globalization appear to play an important yet under-studied role, with potential associations with increased prevalence of overweight and obesity. The limited evidence available also suggests that the association between trade liberalization or globalization and nutritional outcomes might differ substantially across population sub-groups. Overall, our findings suggest that policymakers do not necessarily face a trade-off when considering the implications of trade or economic liberalization for malnutrition in all its forms. On the contrary, a combination of nutrition-sensitive trade policy and adequate regulation of FDI could help reduce all forms of malnutrition. In the context of trade negotiations and agreements it is fundamental, therefore, to protect the policy space for governments to adopt nutrition-sensitive interventions

Reviewing the effectiveness of participatory health research: challenges and possible solutions

Participation in health research is becoming more important as health systems are challenged to contain costs in the face of ageing populations and increased demand for support with chronic and long-term conditions. Partnership working, community engagement and participation in the process of designing research and delivering health interventions are now a major focus for funders, requiring high-quality evaluations of effectiveness. Systematic reviews of these initiatives indicate that they are effective, but providing explanations for how and why participation works is difficult due to thin reporting of the process. This chapter outlines the challenges of conducting reviews of participation in health research, including how to assemble an experienced review team, construct definitions of participation and impact and locate good information on participation in health research. Solutions for reviewing participation are presented, based on international guidance for systematic reviews and practical experiences of conducting reviews on participation and community engagement