Evaluation of a ln tan integral arising in quantum field theory

We analytically evaluate a dilogarithmic integral that is prototypical of volumes of ideal tetrahedra in hyperbolic geometry. We additionally obtain new representations of the Clausen function Cl_2 and the Catalan constant G=Cl_2(\pi/2), as well as new relations between sine and Clausen function values.Comment: 24 pages, no figure

Association between polygenic risk for Alzheimer’s disease, brain structure and cognitive abilities in UK Biobank

Previous studies testing associations between polygenic risk for late-onset Alzheimer’s disease (LOAD-PGR) and brain magnetic resonance imaging (MRI) measures have been limited by small samples and inconsistent consideration of potential confounders. This study investigates whether higher LOAD-PGR is associated with differences in structural brain imaging and cognitive values in a relatively large sample of non-demented, generally healthy adults (UK Biobank). Summary statistics were used to create PGR scores for n = 32,790 participants using LDpred. Outcomes included 12 structural MRI volumes and 6 concurrent cognitive measures. Models were adjusted for age, sex, body mass index, genotyping chip, 8 genetic principal components, lifetime smoking, apolipoprotein (APOE) e4 genotype and socioeconomic deprivation. We tested for statistical interactions between APOE e4 allele dose and LOAD-PGR vs. all outcomes. In fully adjusted models, LOAD-PGR was associated with worse fluid intelligence (standardised beta [β] = −0.080 per LOAD-PGR standard deviation, p = 0.002), matrix completion (β = −0.102, p = 0.003), smaller left hippocampal total (β = −0.118, p = 0.002) and body (β = −0.069, p = 0.002) volumes, but not other hippocampal subdivisions. There were no significant APOE x LOAD-PGR score interactions for any outcomes in fully adjusted models. This is the largest study to date investigating LOAD-PGR and non-demented structural brain MRI and cognition phenotypes. LOAD-PGR was associated with smaller hippocampal volumes and aspects of cognitive ability in healthy adults and could supplement APOE status in risk stratification of cognitive impairment/LOAD

Place attachment in deprived neighbourhoods: The impacts of population turnover and social mix

This paper examines the determinants of individual place attachment, focussing in particular on differences between deprived and others neighbourhoods, and on the impacts of population turnover and social mix. It uses a multi-level modelling approach to take account of both individual- and neighbourhood-level determinants. Data are drawn from a large sample government survey, the Citizenship Survey 2005, to which a variety of neighbourhood-level data have been attached. The paper argues that attachment is significantly lower in more deprived neighbourhoods primarily because these areas have weaker social cohesion but that, in other respects, the drivers of attachment are the same. Turnover has modest direct impacts on attachment through its effect on social cohesion. Social mix has very limited impacts on attachment and the effects vary between social groups. In general, higher status or more dominant groups appear less tolerant of social mix

Plasma microRNA levels differ between endurance and strength athletes

Aim: MicroRNAs (miRNAs) are stable in the circulation and are likely to function in inter-organ communication during a variety of metabolic responses that involve changes in gene expression, including exercise training. However, it is unknown whether differences in circulating-miRNA (c-miRNA) levels are characteristic of training modality. Methods: We investigated whether levels of candidate c-miRNAs differ between elite male athletes of two different training modalities (n = 10 per group) - endurance (END) and strength (STR) - and between these groups and untrained controls (CON; n = 10). Fasted, non-exercised, morning plasma samples were analysed for 14 c-miRNAs (miR-1, miR-16-2, miR-20a-1, miR-21, miR-93, miR-103a, miR-133a, miR-146a, miR-192, miR-206, miR-221, miR-222, miR-451, miR-499). Moreover, we investigated whether c-miRNA levels were associated with quantitative performance-related phenotypes within and between groups. Results: miR-222 was present at different levels in the three participant groups (p = 0.028) with the highest levels being observed in END and the lowest in STR. A number of other c-miRNAs were present at higher levels in END than in STR (relative to STR, ± 1 SEM; miR-222: 1.94 fold (1.73-2.18), p = 0.011; miR-21: 1.56 fold (1.39-1.74), p = 0.013; miR-146a: 1.50 fold (1.38-1.64), p = 0.019; miR-221: 1.51 fold (1.34-1.70), p = 0.026). Regression analyses revealed several associations between candidate c-miRNA levels and strength-related performance measures before and after adjustment for muscle or fat mass, but not following adjustment for group. Conclusion: Certain c-miRNAs (miR-222, miR-21, miR-146a and miR-221) differ between endurance- and resistance-trained athletes and thus have potential as useful biomarkers of exercise training and / or play a role in exercise mode-specific training adaptations. However, levels of these c-miRNAs are probably unrelated to muscle bulk or fat reserves

Mapping and validating predictions of soil bacterial biodiversity using European and national scale datasets

Recent research has highlighted strong correlations between soil edaphic parameters and bacterial biodiversity. Here we seek to explore these relationships across the European Union member states with respect to mapping bacterial biodiversity at the continental scale. As part of the EU FP7 EcoFINDERs project, bacterial communities from 76 soil samples taken across Europe were assessed from eleven countries encompassing Arctic to Southern Mediterranean climes, representing a diverse range of soil types and land uses (grassland, forest and arable land). We found predictable relationships between community biodiversity (ordination site scores) and land use factors as well as soil properties such as pH. Based on the modelled relationship between soil pH and bacterial biodiversity found for the surveyed soils, we were able to predict biodiversity in ∼1000 soils for which soil pH data had been collected as part of national scale monitoring. We then performed interpolative mapping utilising existing EU wide soil pH data to present the first map of bacterial biodiversity across the EU member states. The predictive accuracy of the map was assessed again using the national scale data, but this time contrasting the EU wide spatial predictions with point data on bacterial communities. Generally the maps were useful at predicting broad extremes of biodiversity reflective of low or high pH soils, though predictive accuracy was limited for Britain particularly for organic/acidic soil communities. Spatial accuracy could however be increased by utilising published maps of soil pH calculated using geostatistical approaches at both global and national scales. These findings will contribute to wider efforts to predict and understand the spatial distribution of soil biodiversity at global scales. Further work should focus on enhancing the predictive power of such maps, by harmonising global datasets on soil conditioning parameters, soil properties and biodiversity; and the continued efforts to advance the geostatistical modelling of specific components of soil biodiversity at local to global scales

The impact of sequencing depth on the inferred taxonomic composition and AMR gene content of metagenomic samples

Shotgun metagenomics is increasingly used to characterise microbial communities, particularly for the investigation of antimicrobial resistance (AMR) in different animal and environmental contexts. There are many different approaches for inferring the taxonomic composition and AMR gene content of complex community samples from shotgun metagenomic data, but there has been little work establishing the optimum sequencing depth, data processing and analysis methods for these samples. In this study we used shotgun metagenomics and sequencing of cultured isolates from the same samples to address these issues. We sampled three potential environmental AMR gene reservoirs (pig caeca, river sediment, effluent) and sequenced samples with shotgun metagenomics at high depth (~ 200 million reads per sample). Alongside this, we cultured single-colony isolates of Enterobacteriaceae from the same samples and used hybrid sequencing (short- and long-reads) to create high- quality assemblies for comparison to the metagenomic data. To automate data processing, we developed an open- source software pipeline, ‘ResPipe’

Sex-Stratified Genome-Wide Association Study of Multisite Chronic Pain in UK Biobank

Chronic pain is highly prevalent worldwide and imparts a significant socioeconomic and public health burden. Factors influencing susceptibility to, and mechanisms of, chronic pain development, are not fully understood, but sex is thought to play a significant role, and chronic pain is more prevalent in women than in men. To investigate sex differences in chronic pain, we carried out a sex-stratified genome-wide association study of Multisite Chronic Pain (MCP), a derived chronic pain phenotype, in UK Biobank on 178,556 men and 209,093 women, as well as investigating sex-specific genetic correlations with a range of psychiatric, autoimmune and anthropometric phenotypes and the relationship between sex-specific polygenic risk scores for MCP and chronic widespread pain. We also assessed whether MCP-associated genes showed expression pattern enrichment across tissues. A total of 123 SNPs at five independent loci were significantly associated with MCP in men. In women, a total of 286 genome-wide significant SNPs at ten independent loci were discovered. Meta-analysis of sex-stratified GWAS outputs revealed a further 87 independent associated SNPs. Gene-level analyses revealed sex-specific MCP associations, with 31 genes significantly associated in females, 37 genes associated in males, and a single gene, DCC, associated in both sexes. We found evidence for sex-specific pleiotropy and risk for MCP was found to be associated with chronic widespread pain in a sex-differential manner. Male and female MCP were highly genetically correlated, but at an rg of significantly less than 1 (0.92). All 37 male MCP-associated genes and all but one of 31 female MCP-associated genes were found to be expressed in the dorsal root ganglion, and there was a degree of enrichment for expression in sex-specific tissues. Overall, the findings indicate that sex differences in chronic pain exist at the SNP, gene and transcript abundance level, and highlight possible sex-specific pleiotropy for MCP. Results support the proposition of a strong central nervous-system component to chronic pain in both sexes, additionally highlighting a potential role for the DRG and nociception

Quantitative optical coherence tomography angiography of vascular abnormalities in the living human eye

Retinal vascular diseases are important causes of vision loss. A detailed evaluation of the vascular abnormalities facilitates diagnosis and treatment in these diseases. Optical coherence tomography (OCT) angiography using the highly efficient split-spectrum amplitude decorrelation angiography algorithm offers an alternative to conventional dye-based retinal angiography. OCT angiography has several advantages, including 3D visualization of retinal and choroidal circulations (including the choriocapillaris) and avoidance of dye injection-related complications. Results from six illustrative cases are reported. In diabetic retinopathy, OCT angiography can detect neovascularization and quantify ischemia. In age-related macular degeneration, choroidal neovascularization can be observed without the obscuration of details caused by dye leakage in conventional angiography. Choriocapillaris dysfunction can be detected in the nonneovascular form of the disease, furthering our understanding of pathogenesis. In choroideremia, OCT's ability to show choroidal and retinal vascular dysfunction separately may be valuable in predicting progression and assessing treatment response. OCT angiography shows promise as a noninvasive alternative to dye-based angiography for highly detailed, in vivo, 3D, quantitative evaluation of retinal vascular abnormalities.National Institutes of Health (U.S.) (Grant R01-EY023285)National Institutes of Health (U.S.) (Grant R01-EY024544)National Institutes of Health (U.S.) (Grant DP3 DK104397)National Institutes of Health (U.S.) (Grant R01-EY11289)National Institutes of Health (U.S.) (Grant K08-EY021186)National Institutes of Health (U.S.) (Grant T32-EY23211)National Institutes of Health (U.S.) (Grant P30-EY010572)Clinical and Translational Science Award Grant UL1TR000128Research to Prevent Blindness, Inc. (United States) (Grant and Career Development Award CD-NMT-0914-0659-OHSU)United States. Air Force Office of Scientific Research (Foundation Fighting Blindness Career Development Award FA9550-10-1-0551)German Research Foundation (Grant DFG-HO-1791/11-1)German Research Foundation (Grant DFG-GSC80-SAOT

A specialized learner for inferring structured cis-regulatory modules

BACKGROUND: The process of transcription is controlled by systems of transcription factors, which bind to specific patterns of binding sites in the transcriptional control regions of genes, called cis-regulatory modules (CRMs). We present an expressive and easily comprehensible CRM representation which is capable of capturing several aspects of a CRM's structure and distinguishing between DNA sequences which do or do not contain it. We also present a learning algorithm tailored for this domain, and a novel method to avoid overfitting by controlling the expressivity of the model. RESULTS: We are able to find statistically significant CRMs more often then a current state-of-the-art approach on the same data sets. We also show experimentally that each aspect of our expressive CRM model space makes a positive contribution to the learned models on yeast and fly data. CONCLUSION: Structural aspects are an important part of CRMs, both in terms of interpreting them biologically and learning them accurately. Source code for our algorithm is available at

Adaptive introgression facilitate adaptation to high latitudes in European aspen (Populus tremula L.)

Understanding local adaptation has become a key research area given the ongoing climate challenge and the concomitant requirement to conserve genetic resources. Perennial plants, such as forest trees, are good models to study local adaptation given their wide geographic distribution, largely outcrossing mating systems and demographic histories. We evaluated signatures of local adaptation in European aspen (Populus tremula) across Europe by means of whole genome re-sequencing of a collection of 411 individual trees. We dissected admixture patterns between aspen lineages and observed a strong genomic mosaicism in Scandinavian trees, evidencing different colonization trajectories into the peninsula from Russia, Central and Western Europe. As a consequence of the secondary contacts between populations after the last glacial maximum (LGM), we detected an adaptive introgression event in a genome region of ∼500kb in chromosome 10, harboring a large-effect locus that has previously been shown to contribute to adaptation to the short growing seasons characteristic of northern Scandinavia. Demographic simulations and ancestry inference suggest an Eastern origin - probably Russian - of the adaptive Nordic allele which nowadays is present in a homozygous state at the north of Scandinavia. The strength of introgression and positive selection signatures in this region is a unique feature in the genome. Furthermore, we detected signals of balancing selection, shared across regional populations, that highlight the importance of standing variation as a primary source of alleles that facilitate local adaptation. Our results therefore emphasize the importance of migration-selection balance underlying the genetic architecture of key adaptive quantitative traits