The geography of recent genetic ancestry across Europe

The recent genealogical history of human populations is a complex mosaic formed by individual migration, large-scale population movements, and other demographic events. Population genomics datasets can provide a window into this recent history, as rare traces of recent shared genetic ancestry are detectable due to long segments of shared genomic material. We make use of genomic data for 2,257 Europeans (the POPRES dataset) to conduct one of the first surveys of recent genealogical ancestry over the past three thousand years at a continental scale. We detected 1.9 million shared genomic segments, and used the lengths of these to infer the distribution of shared ancestors across time and geography. We find that a pair of modern Europeans living in neighboring populations share around 10-50 genetic common ancestors from the last 1500 years, and upwards of 500 genetic ancestors from the previous 1000 years. These numbers drop off exponentially with geographic distance, but since genetic ancestry is rare, individuals from opposite ends of Europe are still expected to share millions of common genealogical ancestors over the last 1000 years. There is substantial regional variation in the number of shared genetic ancestors: especially high numbers of common ancestors between many eastern populations likely date to the Slavic and/or Hunnic expansions, while much lower levels of common ancestry in the Italian and Iberian peninsulas may indicate weaker demographic effects of Germanic expansions into these areas and/or more stably structured populations. Recent shared ancestry in modern Europeans is ubiquitous, and clearly shows the impact of both small-scale migration and large historical events. Population genomic datasets have considerable power to uncover recent demographic history, and will allow a much fuller picture of the close genealogical kinship of individuals across the world.Comment: Full size figures available from http://www.eve.ucdavis.edu/~plralph/research.html; or html version at http://ralphlab.usc.edu/ibd/ibd-paper/ibd-writeup.xhtm

The effect of disgust-related side-effects on symptoms of depression and anxiety in people treated for cancer: a moderated mediation model

As maladaptive disgust responses are linked to mental health problems, and cancer patients may experience heightened disgust as a result of treatments they receive, we explored the associations between disgust-related side-effects and symptoms of depression and anxiety in people treated for cancer. One hundred and thirty two (83 women, Mage = 57.48 years) participants answered questions about their treatments, side-effects, disgust responding, and mental health. Experiencing bowel and/or bladder problems, sickness and/or nausea (referred to here as “core” disgust-related side-effects) was significantly related to greater symptoms of depression and borderline increased anxiety. Further, these links were explained by a moderated mediation model, whereby the effects of core disgust side-effects on depression and anxiety were mediated by (physical and behavioural) self-directed disgust, and disgust propensity moderated the effect of core disgust side-effects on self-disgust. These findings stress the importance of emotional responses, like disgust, in psychological adaptation to the side-effects of cancer treatments

Fetus-derived DLK1 is required for maternal metabolic adaptations to pregnancy and is associated with fetal growth restriction.

Pregnancy is a state of high metabolic demand. Fasting diverts metabolism to fatty acid oxidation, and the fasted response occurs much more rapidly in pregnant women than in non-pregnant women. The product of the imprinted DLK1 gene (delta-like homolog 1) is an endocrine signaling molecule that reaches a high concentration in the maternal circulation during late pregnancy. By using mouse models with deleted Dlk1, we show that the fetus is the source of maternal circulating DLK1. In the absence of fetally derived DLK1, the maternal fasting response is impaired. Furthermore, we found that maternal circulating DLK1 levels predict embryonic mass in mice and can differentiate healthy small-for-gestational-age (SGA) infants from pathologically small infants in a human cohort. Therefore, measurement of DLK1 concentration in maternal blood may be a valuable method for diagnosing human disorders associated with impaired DLK1 expression and to predict poor intrauterine growth and complications of pregnancy.M.A.M.C. was supported by a PhD studentship from the Cambridge Centre for Trophoblast Research. Research was supported by grants from the MRC (MR/J001597/1 and MR/L002345/1), the Medical College of Saint Bartholomew's Hospital Trust, a Wellcome Trust Investigator Award, EpigeneSys (FP7 Health-257082), EpiHealth (FP7 Health-278414), a Herchel Smith Fellowship (N.T.) and NIH grant RO1 DK89989. The contents are the authors' sole responsibility and do not necessarily represent official NIH views. We thank G. Burton for invaluable support, and M. Constância and I. Sandovici (University of Cambridge) for the Meox2-cre mice. We are extremely grateful to all of the participants in the Pregnancy Outcome Prediction study. This work was supported by the NIHR Cambridge Comprehensive Biomedical Research Centre (Women's Health theme) and project grants from the MRC (G1100221) and Sands (Stillbirth and Neonatal Death Charity). The study was also supported by GE Healthcare (donation of two Voluson i ultrasound systems for this study) and by the NIHR Cambridge Clinical Research Facility, where all research visits took place.This is the author accepted manuscript. The final version is available from Nature Publishing Group via https://doi.org/10.1038/ng.369

Two Major Autoantibody Clusters in Systemic Lupus Erythematosus

Systemic lupus erythematosus is a chronic autoimmune disease of complex clinical presentation and etiology and is likely influenced by numerous genetic and environmental factors. While a large number of susceptibility genes have been identified, the production of antibodies against a distinct subset of nuclear proteins remains a primary distinguishing characteristic in disease diagnosis. However, the utility of autoantibody biomarkers for disease sub-classification and grouping remains elusive, in part, because of the difficulty in large scale profiling using a uniform, quantitative platform. In the present study serological profiles of several known SLE antigens, including Sm-D3, RNP-A, RNP-70k, Ro52, Ro60, and La, as well as other cytokine and neuronal antigens were obtained using the luciferase immunoprecipitation systems (LIPS) approach. The resulting autoantibody profiles revealed that 88% of a pilot cohort and 98% of a second independent cohort segregated into one of two distinct clusters defined by autoantibodies against Sm/anti-RNP or Ro/La autoantigens, proteins often involved in RNA binding activities. The Sm/RNP cluster was associated with a higher prevalence of serositis in comparison to the Ro/La cluster (P = 0.0022). However, from the available clinical information, no other clinical characteristics were associated with either cluster. In contrast, evaluation of autoantibodies on an individual basis revealed an association between anti-Sm (P = 0.006), RNP-A (P = 0.018) and RNP-70k (P = 0.010) autoantibodies and mucocutaneous symptoms and between anti-RNP-70k and musculoskeletal manifestations (P = 0.059). Serologically active, but clinically quiescent disease also had a higher prevalence of anti-IFN-α autoantibodies. Based on our findings that most SLE patients belong to either a Sm/RNP or Ro/La autoantigen cluster, these results suggest the possibility that alterations in RNA-RNA-binding protein interactions may play a critical role in triggering and/or the pathogenesis of SLE

Engaging communication experts in a Delphi process to identify patient behaviors that could enhance communication in medical encounters

<p>Abstract</p> <p>Background</p> <p>The communication literature currently focuses primarily on improving physicians' verbal and non-verbal behaviors during the medical interview. The Four Habits Model is a teaching and research framework for physician communication that is based on evidence linking specific communication behaviors with processes and outcomes of care. The Model conceptualizes basic communication tasks as "Habits" and describes the sequence of physician communication behaviors during the clinical encounter associated with improved outcomes. Using the Four Habits Model as a starting point, we asked communication experts to identify the verbal communication behaviors of patients that are important in outpatient encounters.</p> <p>Methods</p> <p>We conducted a 4-round Delphi process with 17 international experts in communication research, medical education, and health care delivery. All rounds were conducted via the internet. In round 1, experts reviewed a list of proposed patient verbal communication behaviors within the Four Habits Model framework. The proposed patient verbal communication behaviors were identified based on a review of the communication literature. The experts could: approve the proposed list; add new behaviors; or modify behaviors. In rounds 2, 3, and 4, they rated each behavior for its fit (agree or disagree) with a particular habit. After each round, we calculated the percent agreement for each behavior and provided these data in the next round. Behaviors receiving more than 70% of experts' votes (either agree or disagree) were considered as achieving consensus.</p> <p>Results</p> <p>Of the 14 originally-proposed patient verbal communication behaviors, the experts modified all but 2, and they added 20 behaviors to the Model in round 1. In round 2, they were presented with 59 behaviors and 14 options to remove specific behaviors for rating. After 3 rounds of rating, the experts retained 22 behaviors. This set included behaviors such as asking questions, expressing preferences, and summarizing information.</p> <p>Conclusion</p> <p>The process identified communication tasks and verbal communication behaviors for patients similar to those outlined for physicians in the Four Habits Model. This represents an important step in building a single model that can be applied to teaching patients and physicians the communication skills associated with improved satisfaction and positive outcomes of care.</p

Assessment of fall-related self-efficacy and activity avoidance in people with Parkinson's disease

<p>Abstract</p> <p>Background</p> <p>Fear of falling (FOF) is common in Parkinson's disease (PD), and it is considered a vital aspect of comprehensive balance assessment in PD. FOF can be conceptualized differently. The Falls-Efficacy Scale (FES) assesses fall-related self-efficacy, whereas the Survey of Activities and Fear of Falling in the Elderly (SAFFE) assesses activity avoidance due to the risk of falling. This study aimed at investigating the validity and reliability of FES and SAFFE in people with PD.</p> <p>Methods</p> <p>Seventy-nine people with PD (mean age; 64 years, SD 7.2) completed the Swedish version of FES(S), SAFFE and the physical functioning (PF) scale of the 36-Item Short-Form Health Survey (SF-36). FES(S) and SAFFE were administered twice, with an 8.8 (SD 2.3) days interval. Assumptions for summing item scores into total scores were examined and score reliability (Cronbach's alpha and test-retest reliability) were calculated. Construct validity was assessed by examining the pattern of Spearman correlations (r_s) between the FES(S)/SAFFE and other variables, and by examining differences in FES(S)/SAFFE scores between fallers and non-fallers, genders, and between those reporting FOF and unsteadiness while turning.</p> <p>Results</p> <p>For both scales, item mean scores (and standard deviations) were roughly similar and corrected item-total correlations exceeded 0.4. Reliabilities were ≥0.87. FES(S)-scores correlated strongest (r_s, -0.74, p < 0.001) with SAFFE-scores, whereas SAFFE-scores correlated strongest with PF-scores (r_s, -0.76, p < 0.001). Both scales correlated weakest with age (r_s≤ 0.08). Experiencing falls, unsteadiness while turning, and FOF was associated with lower fall-related self-efficacy and higher activity avoidance.</p> <p>Conclusions</p> <p>This study provides initial support for the score reliability and validity of the FES(S) and SAFFE in people with PD.</p

Ryanodine receptors are part of the myospryn complex in cardiac muscle

The Cardiomyopathy–associated gene 5 (Cmya5) encodes myospryn, a large tripartite motif (TRIM)-related protein found predominantly in cardiac and skeletal muscle. Cmya5 is an expression biomarker for a number of diseases affecting striated muscle and may also be a schizophrenia risk gene. To further understand the function of myospryn in striated muscle, we searched for additional myospryn paralogs. Here we identify a novel muscle-expressed TRIM-related protein minispryn, encoded by Fsd2, that has extensive sequence similarity with the C-terminus of myospryn. Cmya5 and Fsd2 appear to have originated by a chromosomal duplication and are found within evolutionarily-conserved gene clusters on different chromosomes. Using immunoaffinity purification and mass spectrometry we show that minispryn co-purifies with myospryn and the major cardiac ryanodine receptor (RyR2) from heart. Accordingly, myospryn, minispryn and RyR2 co-localise at the junctional sarcoplasmic reticulum of isolated cardiomyocytes. Myospryn redistributes RyR2 into clusters when co-expressed in heterologous cells whereas minispryn lacks this activity. Together these data suggest a novel role for the myospryn complex in the assembly of ryanodine receptor clusters in striated muscle

Parrots Eat Nutritious Foods despite Toxins

Generalist herbivores are challenged not only by the low nitrogen and high indigestibility of their plant foods, but also by physical and chemical defenses of plants. This study investigated the foods of wild parrots in the Peruvian Amazon and asked whether these foods contain dietary components that are limiting for generalist herbivores (protein, lipids, minerals) and in what quantity; whether parrots chose foods based on nutrient content; and whether parrots avoid plants that are chemically defended.We made 224 field observations of free-ranging parrots of 17 species in 8 genera foraging on 102 species of trees in an undisturbed tropical rainforest, in two dry seasons (July-August 1992-1993) and one wet season (January-February1994). We performed laboratory analyses of parts of plants eaten and not eaten by parrots and brine shrimp assays of toxicity as a proxy for vertebrates. Parrots ate seeds, fruits, flowers, leaves, bark, and insect larvae, but up to 70% of their diet comprised seeds of many species of tropical trees, in various stages of ripeness. Plant parts eaten by parrots were rich in protein, lipid, and essential minerals, as well as potentially toxic chemicals. Seeds were higher than other plant materials in protein and lipid and lower in fiber. Large macaws of three species ate foods higher in protein and lipids and lower in fiber compared to plant parts available but not eaten. Macaws ate foods that were lower in phenolic compounds than foods they avoided. Nevertheless, foods eaten by macaws contained measurable levels of toxicity. Macaws did not appear to make dietary selections based on mineral content.Parrots represent a remarkable example of a generalist herbivore that consumes seeds destructively despite plant chemical defenses. With the ability to eat toxic foods, rainforest-dwelling parrots exploited a diversity of nutritious foods, even in the dry season when food was scarce for other frugivores and granivores

Genetic diversity analysis in the section Caulorrhizae (genus Arachis) using microsatellite markers

Diversity in 26 microsatellite loci from section Caulorrhizae germplasm was evaluated by using 33 accessions of A. pintoi Krapov. & W.C. Gregory and ten accessions of Arachis repens Handro. Twenty loci proved to be polymorphic and a total of 196 alleles were detected with an average of 9.8 alleles per locus. The variability found in those loci was greater than the variability found using morphological characters, seed storage proteins and RAPD markers previously used in this germplasm. The high potential of these markers to detect species-specific alleles and discriminate among accessions was demonstrated. The set of microsatellite primer pairs developed by our group for A. pintoi are useful molecular tools for evaluating Section Caulorrhizae germplasm, as well as that of species belonging to other Arachis sections

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente