A meta-analysis of genome-wide association studies of epigenetic age acceleration

Funding: Generation Scotland received core support from the Chief Scientist Office of the Scottish Government Health Directorates (CZD/16/6) and the Scottish Funding Council (HR03006). Genotyping and DNA methylation profiling of the GS samples was carried out by the Genetics Core Laboratory at the Wellcome Trust Clinical Research Facility, Edinburgh, Scotland and was funded by the Medical Research Council UK and the Wellcome Trust (Wellcome Trust Strategic Award “STratifying Resilience and Depression Longitudinally” ((STRADL) Reference 104036/Z/14/Z)). Funding details for the cohorts included in the study by Lu et al. (2018) can be found in their publication. HCW is supported by a JMAS SIM fellowship from the Royal College of Physicians of Edinburgh and by an ESAT College Fellowship from the University of Edinburgh. AMM & HCW acknowledge the support of the Dr. Mortimer and Theresa Sackler Foundation. SH acknowledges support from grant 1U01AG060908-01. REM is supported by Alzheimer’s Research UK major project grant ARUK-PG2017B-10. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Data Availability: Summary statistics from the research reported in the manuscript will be made available immediately following publication on the Edinburgh Data Share portal with a permanent digital object identifier (DOI). According to the terms of consent for Generation Scotland participants, requests for access to the individual-level data must be reviewed by the GS Access Committee ([email protected]). Individual-level data are not immediately available, due to confidentiality considerations and our legal obligation to protect personal information. These data will, however, be made available upon request and after review by the GS access committee, once ethical and data governance concerns regarding personal data have been addressed by the receiving institution through a Data Transfer Agreement.Peer reviewedPublisher PD

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

British Romanticism and the Global Climate

As a result of developments in the meteorological and geological sciences, the Romantic period saw the gradual emergence of attempts to understand the climate as a dynamic global system that could potentially be affected by human activity. This chapter examines textual responses to climate disruption cause by the Laki eruption of 1783 and the Tambora eruption of 1815. During the Laki haze, writers such as Horace Walpole, Gilbert White, and William Cowper found in Milton a powerful way of understanding the entanglements of culture and climate at a time of national and global crisis. Apocalyptic discourse continued to resonate during the Tambora crisis, as is evident in eyewitness accounts of the eruption, in the utopian predictions of John Barrow and Eleanor Anne Porden, and in the grim speculations of Byron’s ‘Darkness’. Romantic writing offers a powerful analogue for thinking about climate change in the Anthropocene

Kremen1 regulates the regenerative capacity of support cells and mechanosensory hair cells in the zebrafish lateral line

Summary: Mechanosensory hair cells in the inner ear mediate the sensations of hearing and balance, and in the specialized lateral line sensory system of aquatic vertebrates, the sensation of water movement. In mammals, hair cells lack the ability to regenerate following damage, resulting in sensory deficits. In contrast, non-mammalian vertebrates, such as zebrafish, can renew hair cells throughout their lifespan. Wnt signaling is required for development of inner ear and lateral line hair cells and regulates regeneration. Kremen1 inhibits Wnt signaling and hair cell formation, though its role in regeneration is unknown. We used a zebrafish kremen1 mutant line to show overactive Wnt signaling results in supernumerary support cells and hair cell regeneration without increased proliferation, in contrast with the previously described role of Wnt signaling during hair cell regeneration. This work allows us to understand the biology of mechanosensory hair cells and how regeneration might be promoted following damage

An evaluation of the impact and effectiveness of environmental legislation in small and medium-sized enterprises: experiences from the UK

With Small- and Medium-Sized Enterprises (SMEs) accounting for 99.7% of the 4.7m UK businesses, they can have a huge collective impact on the environment, which in turn, is increasingly regulated. This study investigated the impact and effectiveness of environmental legislation on UK SMEs as well as determining if ‘compliance’ results in improved environmental protection. Interviews were conducted with SME management, site staff, regulators, policy officials and support organisations. Forty-four SMEs from the north-west of England participated in the study and overall, a total of 99 individuals were interviewed. The study clearly indicates that the impact of environmental legislation on SMEs is overstated and impact increased commensurate with effort to comply and enforcement action. Only 1 of the SMEs studied had been prosecuted and only 2 had been inspected. Compliance issues identified in those SMEs subject to direct regulation did not correlate with previous compliance audits conducted. In general, SMEs had poor awareness of compliance issues; non-compliance was only really recognised and acknowledged if identified by a regulator and only regarded as serious if prosecuted. Regulation of the environment is clearly only effective if complied with; understanding compliance levels can help measure the link between legislation and environmental protection. The effectiveness of environmental legislation can only be understood if SMEs are subject to regular regulatory contact. Recommendations to improve SME compliance control systems are provided