Synthetic tethered silver nanoparticles on reduced graphene oxide for alkaline oxygen reduction catalysis

There is currently an enormous drive to move away from the use of Pt group metals in catalysis, particularly for fuel cells, because of their increasing rarity and cost. Simultaneously, there have been advances in the application of graphene supported nanoparticular catalysts. However, these Pt-free, graphene supported catalysts can be complex to produce, show poor catalytic activity and degrade quickly due to particle agglomeration or isolation. Herein, we report a one-pot synthesis of silver nanoparticles (NPs) tethered to a reduced graphene oxide (rGO) template via organic linkages. This is one of the few silver precursor formations that have been combined with graphene oxide (GO) to simultaneously establish linkage binding sites, reduce GO and yield tethered nanoparticles. These materials are shown to efficiently catalyze the oxygen reduction reaction in alkaline environments, with aminoethanol linkages to 21.55 ± 2.88 nm Ag particles exhibiting the highest catalytic activity via the four-electron pathway. This method, therefore, offers a straightforward route to produce effective catalysts from inexpensive precursors, which could be developed further for significant industrial application

Anion Vacancy Regulated Sodium/Potassium Intercalation in Potassium Prussian Blue Analog Cathodes for Hybrid Sodium-Ion Batteries

Fe-based potassium Prussian blue analogs (K-PBAs) are commonly used as K-ion battery (KIB) cathodes. Interestingly, K-PBAs are appealing cathodes for Na-ion batteries (NIBs). In a hybrid NIB cell, where Na-ion is in the electrolyte and K-ion is in the PBA cathode, cation intercalation and electrochemical performance of the cathode can be significantly affected by [Fe(CN)6]4− anion vacancy. This work studies the effect of anion vacancy in K-PBAs on regulating K-ion/Na-ion intercalation mechanism in hybrid NIB cells, by comparing two K-PBA cathodes with different vacancy contents. The results demonstrate that introducing a level of anion vacancy can maximize the number of K-ion intercalation sites and enhance K-ion diffusion in the PBA framework. This facilitates K-ion intercalation and suppresses Na-ion intercalation, resulting in a K-ion-dominated and high-discharge-voltage ion storage process in the hybrid NIB cell. The K-PBA cathode with 20% anion vacancy delivers 128 mAh g−1 at 25 mA g−1 and 67 mAh g−1 at 1000 mA g−1, as well as retains 89% and 81% capacity after 100 and 300 cycles, respectively. It completely outperforms the counterpart with 7% anion vacancy, which exhibits increased Na-ion intercalation but overall deteriorated ion storage

Thirty loci identified for heart rate response to exercise and recovery implicate autonomic nervous system.

Impaired capacity to increase heart rate (HR) during exercise (ΔHRex), and a reduced rate of recovery post-exercise (ΔHRrec) are associated with higher cardiovascular mortality rates. Currently, the genetic basis of both phenotypes remains to be elucidated. We conduct genome-wide association studies (GWASs) for ΔHRex and ΔHRrec in ~40,000 individuals, followed by replication in ~27,000 independent samples, all from UK Biobank. Six and seven single-nucleotide polymorphisms for ΔHRex and ΔHRrec, respectively, formally replicate. In a full data set GWAS, eight further loci for ΔHRex and nine for ΔHRrec are genome-wide significant (P ≤ 5 × 10-8). In total, 30 loci are discovered, 8 being common across traits. Processes of neural development and modulation of adrenergic activity by the autonomic nervous system are enriched in these results. Our findings reinforce current understanding of HR response to exercise and recovery and could guide future studies evaluating its contribution to cardiovascular risk prediction.This research has been conducted using the UK Biobank Resource (application 8256—Understanding genetic influences in the response of the cardiac electrical system to exercise) and is supported by Medical Research Council grant MR/N025083/1. We also wish to acknowledge the support of the NIHR Cardiovascular Biomedical Research Centre at Barts and Queen Mary University of London, UK. J.R. acknowledges support from the People Programme (Marie Curie Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under REA grant agreement no. 608765. P.D.L. acknowledges support from the UCLH Biomedicine NIHR, Barts Heart Centre BRC. M.O. is supported by an IEF 2013 Marie Curie fellowship. B.M. holds an MRC eMedLab Medical Bioinformatics Career Development Fellowship, funded from award MR/L016311/1. This project was enabled through access to the MRC eMedLab Medical Bioinformatics infrastructure, award MR/L016311/1

Genome-Wide Interaction Analysis with DASH Diet Score Identified Novel Loci for Systolic Blood Pressure.

OBJECTIVE: We examined interactions between genotype and a Dietary Approaches to Stop Hypertension (DASH) diet score in relation to systolic blood pressure (SBP). METHODS: We analyzed up to 9,420,585 biallelic imputed single nucleotide polymorphisms (SNPs) in up to 127,282 individuals of six population groups (91% of European population) from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (CHARGE; n=35,660) and UK Biobank (n=91,622) and performed European population-specific and cross-population meta-analyses. RESULTS: We identified three loci in European-specific analyses and an additional four loci in cross-population analyses at P for interaction < 5e-8. We observed a consistent interaction between rs117878928 at 15q25.1 (minor allele frequency = 0.03) and the DASH diet score (P for interaction = 4e-8; P for heterogeneity = 0.35) in European population, where the interaction effect size was 0.42±0.09 mm Hg (P for interaction = 9.4e-7) and 0.20±0.06 mm Hg (P for interaction = 0.001) in CHARGE and the UK Biobank, respectively. The 1 Mb region surrounding rs117878928 was enriched with cis-expression quantitative trait loci (eQTL) variants (P = 4e-273) and cis-DNA methylation quantitative trait loci (mQTL) variants (P = 1e-300). While the closest gene for rs117878928 is MTHFS, the highest narrow sense heritability accounted by SNPs potentially interacting with the DASH diet score in this locus was for gene ST20 at 15q25.1. CONCLUSION: We demonstrated gene-DASH diet score interaction effects on SBP in several loci. Studies with larger diverse populations are needed to validate our findings

Prognostic markers in cancer: the evolution of evidence from single studies to meta-analysis, and beyond

In oncology, prognostic markers are clinical measures used to help elicit an individual patient's risk of a future outcome, such as recurrence of disease after primary treatment. They thus facilitate individual treatment choice and aid in patient counselling. Evidence-based results regarding prognostic markers are therefore very important to both clinicians and their patients. However, there is increasing awareness that prognostic marker studies have been neglected in the drive to improve medical research. Large protocol-driven, prospective studies are the ideal, with appropriate statistical analysis and clear, unbiased reporting of the methods used and the results obtained. Unfortunately, published prognostic studies rarely meet such standards, and systematic reviews and meta-analyses are often only able to draw attention to the paucity of good-quality evidence. We discuss how better-quality prognostic marker evidence can evolve over time from initial exploratory studies, to large protocol-driven primary studies, and then to meta-analysis or even beyond, to large prospectively planned pooled analyses and to the initiation of tumour banks. We highlight articles that facilitate each stage of this process, and that promote current guidelines aimed at improving the design, analysis, and reporting of prognostic marker research. We also outline why collaborative, multi-centre, and multi-disciplinary teams should be an essential part of future studies

Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease.

The 3-dimensional spatial and 2-dimensional frontal QRS-T angles are measures derived from the vectorcardiogram. They are independent risk predictors for arrhythmia, but the underlying biology is unknown. Using multi-ancestry genome-wide association studies we identify 61 (58 previously unreported) loci for the spatial QRS-T angle (N = 118,780) and 11 for the frontal QRS-T angle (N = 159,715). Seven out of the 61 spatial QRS-T angle loci have not been reported for other electrocardiographic measures. Enrichments are observed in pathways related to cardiac and vascular development, muscle contraction, and hypertrophy. Pairwise genome-wide association studies with classical ECG traits identify shared genetic influences with PR interval and QRS duration. Phenome-wide scanning indicate associations with atrial fibrillation, atrioventricular block and arterial embolism and genetically determined QRS-T angle measures are associated with fascicular and bundle branch block (and also atrioventricular block for the frontal QRS-T angle). We identify potential biology involved in the QRS-T angle and their genetic relationships with cardiovascular traits and diseases, may inform future research and risk prediction

Exome-chip meta-analysis identifies novel loci associated with cardiac conduction, including ADAMTS6

Background: Genome-wide association studies conducted on QRS duration, an electrocardiographic measurement associated with heart failure and sudden cardiac death, have led to novel biological insights into cardiac function. However, the variants identified fall predominantly in non-coding regions and their underlying mechanisms remain unclear.Results: Here, we identify putative functional coding variation associated with changes in the QRS interval duration by combining Illumina HumanExome BeadChip genotype data from 77,898 participants of European ancestry and 7695 of African descent in our discovery cohort, followed by replication in 111,874 individuals of European ancestry from the UK Biobank and deCODE cohorts. We identify ten novel loci, seven within coding regions, including ADAMTS6, significantly associated with QRS duration in gene-based analyses. ADAMTS6 encodes a secreted metalloprotease of currently unknown function. In vitro validation analysis shows that the QRS-associated variants lead to impaired ADAMTS6 secretion and loss-of function analysis in mice demonstrates a previously unappreciated role for ADAMTS6 in connexin 43 gap junction expression, which is essential for myocardial conduction.Conclusions: Our approach identifies novel coding and non-coding variants underlying ventricular depolarization and provides a possible mechanism for the ADAMTS6-associated conduction changes

Discovery of novel heart rate-associated loci using the Exome Chip

Resting heart rate is a heritable trait, and an increase in heart rate is associated with increased mortality risk. Genome-wide association study analyses have found loci associated with resting heart rate, at the time of our study these loci explained 0.9% of the variation. This study aims to discover new genetic loci associated with heart rate from Exome Chip meta-analyses. Heart rate was measured from either elecrtrocardiograms or pulse recordings. We meta-analysed heart rate association results from 104 452 European-ancestry individuals from 30 cohorts, genotyped using the Exome Chip. Twenty-four variants were selected for follow-up in an independent dataset (UK Biobank, N = 134 251). Conditional and gene-based testing was undertaken, and variants were investigated with bioinformatics methods.We discovered five novel heart rate loci, and one new independent low-frequency non-synonymous variant in an established heart rate locus (KIAA1755). Lead variants in four of the novel loci are non-synonymous variants in the genes C10orf71, DALDR3, TESK2 and SEC31B. The variant at SEC31B is significantly associated with SEC31B expression in heart and tibial nerve tissue. Further candidate genes were detected from long-range regulatory chromatin interactions in heart tissue (SCD, SLF2 and MAPK8). We observed significant enrichment in DNase I hypersensitive sites in fetal heart and lung. Moreover, enrichment was seen for the first time in human neuronal progenitor cells (derived from embryonic stem cells) and fetal muscle samples by including our novel variants.Our findings advance the knowledge of the genetic architecture of heart rate, and indicate new candidate genes for follow-up functional studies

Genetic analyses of the electrocardiographic QT interval and its components identify additional loci and pathways.

The QT interval is an electrocardiographic measure representing the sum of ventricular depolarization and repolarization, estimated by QRS duration and JT interval, respectively. QT interval abnormalities are associated with potentially fatal ventricular arrhythmia. Using genome-wide multi-ancestry analyses (>250,000 individuals) we identify 177, 156 and 121 independent loci for QT, JT and QRS, respectively, including a male-specific X-chromosome locus. Using gene-based rare-variant methods, we identify associations with Mendelian disease genes. Enrichments are observed in established pathways for QT and JT, and previously unreported genes indicated in insulin-receptor signalling and cardiac energy metabolism. In contrast for QRS, connective tissue components and processes for cell growth and extracellular matrix interactions are significantly enriched. We demonstrate polygenic risk score associations with atrial fibrillation, conduction disease and sudden cardiac death. Prioritization of druggable genes highlight potential therapeutic targets for arrhythmia. Together, these results substantially advance our understanding of the genetic architecture of ventricular depolarization and repolarization