Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Broadening the taxonomic scope of coral reef palaeoecological studies using ancient DNA

Marine environments face acute pressures from human impacts, often resulting in substantial changes in community structure. On the inshore Great Barrier Reef (GBR), palaeoecological studies show the collapse of the previously dominant coral Acropora from the impacts of degraded water quality associated with European colonization. Even more dramatic impacts can result in the replacement of corals by fleshy macroalgae on modern reefs, but their past distribution is unknown because they leave no fossil record. Here, we apply DNA metabarcoding and high-throughput sequencing of the 18S rDNA gene on palaeoenvironmental DNA (aeDNA) derived from sediment cores at two sites on Pandora Reef (GBR), to enhance palaeoecological studies by incorporating key soft-bodied taxa, including macroalgae. We compared temporal trends in this aeDNA record with those of coral genera derived from macrofossils. Multivariate analysis of 12 eukaryotic groups from the aeDNA community showed wide variability over the past 750 years. The occurrence of brown macroalgae was negatively correlated only with the dominant coral at both sites. The occurrence of coralline and green macroalgae was positively correlated with only the dominant coral at one of the sites, where we also observed a significant association between the whole coral community and the occurrence of each of the three macroalgae groups. Our results demonstrate that reef sediments can provide a valuable archive for understanding the past distribution and occurrence of important soft-bodied reef dwellers. Combining information from fossils and aeDNA provides an enhanced understanding of temporal changes of reefs ecosystems at decadal to millennial timescales.Maria del Carmen Gomez Cabrera, Jennifer M. Young, George Roff, Timothy Staples, Juan Carlos Ortiz, John M. Pandolfi, Alan Coope

Dactl - an Experimental Graph Rewriting Language

Dactl is an experimental language programming language based on fine grain graph transformations. It was developed in the context of a large parallel reduction machine project. The design of the language is outlined, and examples given of its use both as a compiler target language and as a programming language. Dactl has a formal semantics and stable implementations on a number of platforms

On the Adequacy of Graph Rewriting for Stimulating Term Rewriting

Several authors have investigated the correspondence between graph rewriting and term rewriting. Almost invariably they have considered only acyclic graphs. Yet cyclic graphs naturally arise from certain optimisations in implementing functional languages. They correspond to infinite terms, and their reductions correspond to transfinite term reduction sequences, which have recently received detailed attention. We formalise the close correspondence between finitary cyclic graph rewriting and a restricted form of infinitary term rewriting, called rational term rewriting. This subsumes the known relation between finitary acyclic graph rewriting and finitary term rewriting. Surprisingly, the correspondence breaks down for general infinitary rewriting. We present an example showing that infinitary term rewriting is strictly more powerful than infinitary graph rewriting. The study also clarifies the technical difficulties resulting from the combination of collapsing rewrite rules and cyclic g..