Self-Association of an Activating Natural Killer Cell Receptor, KIR2DS1

As a major component of the innate immune system, natural killer cells are responsible for activating the cytolytic killing of certain pathogen-infected or tumor cells. The self-recognition of natural killer cells is achieved in part by the killer cell immunoglobulin-like receptors (KIRs) protein family. In the current study, using a suite of biophysical methods, we investigate the self-association of an activating KIR, KIR2DS1. This KIR is of particular interest because when in the presence of the HLA-Cw6 protein, KIR2DS1 becomes a major risk factor for psoriasis, an autoimmune chronic skin disease. Using circular dichroism spectroscopy, dynamic light scattering, and atomic force microscopy, we reveal that KIR2DS1 self-associates in a well-defined fashion. Our novel results on an activating KIR allow us to suggest a working model for the KIR2DS1- HLA class I molecular mechanism

Methodology in conducting a systematic review of systematic reviews of healthcare interventions

<p>Abstract</p> <p>Background</p> <p>Hundreds of studies of maternity care interventions have been published, too many for most people involved in providing maternity care to identify and consider when making decisions. It became apparent that systematic reviews of individual studies were required to appraise, summarise and bring together existing studies in a single place. However, decision makers are increasingly faced by a plethora of such reviews and these are likely to be of variable quality and scope, with more than one review of important topics. Systematic reviews (or overviews) of reviews are a logical and appropriate next step, allowing the findings of separate reviews to be compared and contrasted, providing clinical decision makers with the evidence they need.</p> <p>Methods</p> <p>The methods used to identify and appraise published and unpublished reviews systematically, drawing on our experiences and good practice in the conduct and reporting of systematic reviews are described. The process of identifying and appraising all published reviews allows researchers to describe the quality of this evidence base, summarise and compare the review's conclusions and discuss the strength of these conclusions.</p> <p>Results</p> <p>Methodological challenges and possible solutions are described within the context of (i) sources, (ii) study selection, (iii) quality assessment (i.e. the extent of searching undertaken for the reviews, description of study selection and inclusion criteria, comparability of included studies, assessment of publication bias and assessment of heterogeneity), (iv) presentation of results, and (v) implications for practice and research.</p> <p>Conclusion</p> <p>Conducting a systematic review of reviews highlights the usefulness of bringing together a summary of reviews in one place, where there is more than one review on an important topic. The methods described here should help clinicians to review and appraise published reviews systematically, and aid evidence-based clinical decision-making.</p

Climatic history of the northeastern United States during the past 3000 years

Many ecosystem processes that influence Earth system feedbacks – vegetation growth, water and nutrient cycling, disturbance regimes – are strongly influenced by multidecadal- to millennial-scale climate variations that cannot be directly observed. Paleoclimate records provide information about these variations, forming the basis of our understanding and modeling of them. Fossil pollen records are abundant in the NE US, but cannot simultaneously provide information about paleoclimate and past vegetation in a modeling context because this leads to circular logic. If pollen data are used to constrain past vegetation changes, then the remaining paleoclimate archives in the northeastern US (NE US) are quite limited. Nonetheless, a growing number of diverse reconstructions have been developed but have not yet been examined together. Here we conduct a systematic review, assessment, and comparison of paleotemperature and paleohydrological proxies from the NE US for the last 3000 years. Regional temperature reconstructions (primarily summer) show a long-term cooling trend (1000 BCE–1700 CE) consistent with hemispheric-scale reconstructions, while hydroclimate data show gradually wetter conditions through the present day. Multiple proxies suggest that a prolonged, widespread drought occurred between 550 and 750 CE. Dry conditions are also evident during the Medieval Climate Anomaly, which was warmer and drier than the Little Ice Age and drier than today. There is some evidence for an acceleration of the longer-term wetting trend in the NE US during the past century; coupled with an abrupt shift from decreasing to increasing temperatures in the past century, these changes could have wide-ranging implications for species distributions, ecosystem dynamics, and extreme weather events. More work is needed to gather paleoclimate data in the NE US to make inter-proxy comparisons and to improve estimates of uncertainty in reconstructions

Reported frequency of physical activity in a large epidemiological study: relationship to specific activities and repeatability over time

<p>Abstract</p> <p>Background</p> <p>How overall physical activity relates to specific activities and how reported activity changes over time may influence interpretation of observed associations between physical activity and health. We examine the relationships between various physical activities self-reported at different times in a large cohort study of middle-aged UK women.</p> <p>Methods</p> <p>At recruitment, Million Women Study participants completed a baseline questionnaire including questions on frequency of strenuous and of any physical activity. About 3 years later 589,896 women also completed a follow-up questionnaire reporting the hours they spent on a range of specific activities. Time spent on each activity was used to estimate the associated excess metabolic equivalent hours (MET-hours) and this value was compared across categories of physical activity reported at recruitment. Additionally, 18,655 women completed the baseline questionnaire twice, at intervals of up to 4 years; repeatability over time was assessed using the weighted kappa coefficient (κ_weighted) and absolute percentage agreement.</p> <p>Results</p> <p>The average number of hours per week women reported doing specific activities was 14.0 for housework, 4.5 for walking, 3.0 for gardening, 0.2 for cycling, and 1.4 for all strenuous activity. Time spent and the estimated excess MET-hours associated with each activity increased with increasing frequency of any or strenuous physical activity reported at baseline (tests for trend, P < 0.003), although the associations for housework were by far the weakest (Spearman correlations, 0.01 and -0.03 respectively for housework, and 0.11-0.37 for all other activities). Repeatability of responses to physical activity questions on the baseline questionnaire declined significantly over time. For strenuous activity, absolute agreement was 64% (κ_weighted= 0.71) for questionnaires administered less than 6 months apart, and 52% (κ_weighted= 0.51) for questionnaires more than 2 years apart. Corresponding values for any physical activity were 57% (κ_weighted= 0.67) and 47% (κ_weighted= 0.58).</p> <p>Conclusions</p> <p>In this cohort, responses to simple questions on the frequency of any physical activity and of strenuous activity asked at baseline were associated with hours spent on specific activities and the associated estimated excess MET-hours expended, reported 3 years later. The weakest associations were with housework. Agreement for identical questions asked on two occasions about the frequency of physical activity decreased over time.</p

A cross-sectional study examining predictors of visit frequency to local green space and the impact this has on physical activity levels

Background Lack of physical activity (PA) is a growing public health concern. There is a growing body of literature that suggests a positive relationship may exist between the amount of local green space near one?s home and PA levels. For instance, park proximity has been shown to predict PA levels amongst certain populations. However, there is little evidence for the role of relatedness towards nature and perceptions of local green space on this relationship. The aim of this study was to examine, in a National UK sample, whether subjective indices associated with local green space were better predictors of visit frequency to local green space and PA levels compared to objectively measured quantity of local green space. Methods A cross-sectional survey was designed. From a random sample, 2079 working age adults responded to an online survey in September 2011. Demographics, self-reported PA, objective measures of the local environment (including local green space, road coverage, and environmental deprivation), were assessed in conjunction with perceptions of local green space and nature relatedness. Quantity of local green space was assessed by cross-referencing respondents? home postcodes with general land use databases. Regression models were conducted to assess which of our independent variables best predicted visit frequency to local green space and/or meeting PA guidelines. In addition, an ordinal regression was run to examine the relationship between visit frequency to local green space and the likelihood of meeting national PA guidelines. Results Nature relatedness was the strongest predictor for both visit frequency to local green space and meeting PA guidelines. Results show that perceived quality is a better predictor of visit frequency to local green space than objective quantity of local green space. The odds of achieving the recommended amount of PA was over four times greater for people who visited local green space once per week compared to never going (OR 4.151; 95 % CI, 2.40 to 7.17). Conclusions These results suggest that perceptions of local green space and nature relatedness play an important role in the relationship between local green space and PA. Considering the known health benefits of PA, our results are potentially important for public health interventions, policy making and environmental planning