•An optimal spatial scale for examining greenspace cooling effects was identified.•The effect of greenspace configuration on the land surface temperature was quantified.•Spatial configuration of a ...mainland-island greenspace enhances the cooling effect.•Fragmented greenspace is also effective for cooling given a fixed amount of forest cover.•Greenspace cooling intensity can indicate cool island characteristics well.
Urban areas will experience the greatest increases in temperature resulting from climate change due to the urban heat island (UHI) effect. Urban greenspace mitigates the UHI and provides cooler microclimates. Field research has established that temperatures within parks or beneath trees can be cooler than in non-greenspaces, but little is known about the effects of the spatial pattern of greenspace on urban temperatures or the optimal spatial patterns needed to cool an urban environment. Here, urban cool islands (UCIs) and greenspace in Nanjing, China were identified from satellite data and the relationship between them analyzed using correlation analyses. The results indicate the following: (1) Areas with a higher percentage of forest-vegetation experience a greater cooling effect and a 10% increase in forest-vegetation area resulted in a decrease of about 0.83°C in surface temperature; (2) A correlation analysis between mean patch size, patch density, and an aggregation index of forest vegetation with temperature reduction showed that for a fixed amount of forest vegetation, fragmented greenspaces also provide effective cooling; (3) The spatial pattern of UCIs was strongly correlated with greenspace patterns; a mainland-island greenspace spatial configuration provided an efficient means of enhancing the cooling effects; and (4) the intensity of the cooling effect was reflected in cool island characteristics. These findings will support better prediction of the effects of specific amounts and spatial arrangements of greenspace, helping city managers and planners mitigate increasing temperatures associated with climate change.
Schizophrenia is a debilitating psychiatric disorder with approximately 1% lifetime risk globally. Large-scale schizophrenia genetic studies have reported primarily on European ancestry samples, ...potentially missing important biological insights. Here, we report the largest study to date of East Asian participants (22,778 schizophrenia cases and 35,362 controls), identifying 21 genome-wide-significant associations in 19 genetic loci. Common genetic variants that confer risk for schizophrenia have highly similar effects between East Asian and European ancestries (genetic correlation = 0.98 ± 0.03), indicating that the genetic basis of schizophrenia and its biology are broadly shared across populations. A fixed-effect meta-analysis including individuals from East Asian and European ancestries identified 208 significant associations in 176 genetic loci (53 novel). Trans-ancestry fine-mapping reduced the sets of candidate causal variants in 44 loci. Polygenic risk scores had reduced performance when transferred across ancestries, highlighting the importance of including sufficient samples of major ancestral groups to ensure their generalizability across populations.
The rate of glycolytic metabolism changes during differentiation of human embryonic stem cells (hESCs) and reprogramming of somatic cells to pluripotency. However, the functional contribution of ...glycolytic metabolism to the pluripotent state is unclear. Here we show that naive hESCs exhibit increased glycolytic flux, MYC transcriptional activity, and nuclear N-MYC localization relative to primed hESCs. This status is consistent with the inner cell mass of human blastocysts, where MYC transcriptional activity is higher than in primed hESCs and nuclear N-MYC levels are elevated. Reduction of glycolysis decreases self-renewal of naive hESCs and feeder-free primed hESCs, but not primed hESCs grown in feeder-supported conditions. Reduction of glycolysis in feeder-free primed hESCs also enhances neural specification. These findings reveal associations between glycolytic metabolism and human naive pluripotency and differences in the metabolism of feeder-/feeder-free cultured hESCs. They may also suggest methods for regulating self-renewal and initial cell fate specification of hESCs.
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•Naive hESCs show increased glycolysis compared to primed counterparts•High nuclear N-MYC is associated with human naive pluripotency•MEF-secreted factors make primed hESCs less reliant on glucose for proliferation•Reduction of glycolysis in feeder-free primed hESCs enhances neural specification
Gu et al. examine the associations between glycolytic metabolism and the pluripotency state of hESCs under different naive and primed growth conditions. They identify differences in the metabolic state and highlight potential metabolic approaches for regulating self-renewal and initial cell fate specification of hESCs.
There are many differences in arterial diseases between men and women, including prevalence, clinical manifestations, treatments, and prognosis. The new policy of the National Institutes of Health, ...which requires the inclusion of sex as a biological variable for preclinical studies, aims to foster new mechanistic insights and to enhance our understanding of sex differences in human diseases. The purpose of this statement is to suggest guidelines for designing and reporting sex as a biological variable in animal models of atherosclerosis, thoracic and abdominal aortic aneurysms, and peripheral arterial disease. We briefly review sex differences of these human diseases and their animal models, followed by suggestions on experimental design and reporting of animal studies for these vascular pathologies.
Updates of Recent Aortic Aneurysm Research Davis, Frank M; Daugherty, Alan; Lu, Hong S
Arteriosclerosis, thrombosis, and vascular biology,
2019-March, 2019-03-00, 20190301, Letnik:
39, Številka:
3
Journal Article
As a key variance partitioning tool, linear mixed models (LMMs) using genome-based restricted maximum likelihood (GREML) allow both fixed and random effects. Classic LMMs assume independence between ...random effects, which can be violated, causing bias. Here we introduce a generalized GREML, named CORE GREML, that explicitly estimates the covariance between random effects. Using extensive simulations, we show that CORE GREML outperforms the conventional GREML, providing variance and covariance estimates free from bias due to correlated random effects. Applying CORE GREML to UK Biobank data, we find, for example, that the transcriptome, imputed using genotype data, explains a significant proportion of phenotypic variance for height (0.15, p-value = 1.5e-283), and that these transcriptomic effects correlate with the genomic effects (genome-transcriptome correlation = 0.35, p-value = 1.2e-14). We conclude that the covariance between random effects is a key parameter for estimation, especially when partitioning phenotypic variance by multi-omics layers.
Abstract
Summary
Genome-wide association study (GWAS) analyses, at sufficient sample sizes and power, have successfully revealed biological insights for several complex traits. RICOPILI, an ...open-sourced Perl-based pipeline was developed to address the challenges of rapidly processing large-scale multi-cohort GWAS studies including quality control (QC), imputation and downstream analyses. The pipeline is computationally efficient with portability to a wide range of high-performance computing environments. RICOPILI was created as the Psychiatric Genomics Consortium pipeline for GWAS and adopted by other users. The pipeline features (i) technical and genomic QC in case-control and trio cohorts, (ii) genome-wide phasing and imputation, (iv) association analysis, (v) meta-analysis, (vi) polygenic risk scoring and (vii) replication analysis. Notably, a major differentiator from other GWAS pipelines, RICOPILI leverages on automated parallelization and cluster job management approaches for rapid production of imputed genome-wide data. A comprehensive meta-analysis of simulated GWAS data has been incorporated demonstrating each step of the pipeline. This includes all the associated visualization plots, to allow ease of data interpretation and manuscript preparation. Simulated GWAS datasets are also packaged with the pipeline for user training tutorials and developer work.
Availability and implementation
RICOPILI has a flexible architecture to allow for ongoing development and incorporation of newer available algorithms and is adaptable to various HPC environments (QSUB, BSUB, SLURM and others). Specific links for genomic resources are either directly provided in this paper or via tutorials and external links. The central location hosting scripts and tutorials is found at this URL: https://sites.google.com/a/broadinstitute.org/RICOPILI/home
Supplementary information
Supplementary data are available at Bioinformatics online.
Summary Sex chromosome aneuploidies are a common group of disorders that are characterised by an abnormal number of X or Y chromosomes. However, many individuals with these disorders are not ...diagnosed, despite established groups of core features that include aberrant brain development and function. Clinical presentations often include characteristic profiles of intellectual ability, motor impairments, and rates of neurological and psychiatric disorders that are higher than those of the general population. Advances in genetics and neuroimaging have substantially expanded knowledge of potential mechanisms that underlie these phenotypes, including a putative dose effect of sex chromosome genes on neuroanatomical structures and cognitive abilities. Continuing attention to emerging trends in research of sex chromosome aneuploidies is important for clinicians because it informs appropriate management of these common genetic disorders. Furthermore, improved understanding of underlying neurobiological processes has much potential to elucidate sex-related factors associated with neurological and psychiatric disease in general.
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