University of Exeter

About: University of Exeter is a education organization based out in Exeter, United Kingdom. It is known for research contribution in the topics: Population & Context (language use). The organization has 15820 authors who have published 50650 publications receiving 1793046 citations. The organization is also known as: Exeter University & University of the South West of England.

Emergence and global spread of epidemic healthcare-associated Clostridium difficile.

Abstract: Epidemic C. difficile (027/BI/NAP1) has rapidly emerged in the past decade as the leading cause of antibiotic-associated diarrhea worldwide. However, the key events in evolutionary history leading to its emergence and the subsequent patterns of global spread remain unknown. Here, we define the global population structure of C. difficile 027/BI/NAP1 using whole-genome sequencing and phylogenetic analysis. We show that two distinct epidemic lineages, FQR1 and FQR2, not one as previously thought, emerged in North America within a relatively short period after acquiring the same fluoroquinolone resistance-conferring mutation and a highly related conjugative transposon. The two epidemic lineages showed distinct patterns of global spread, and the FQR2 lineage spread more widely, leading to healthcare-associated outbreaks in the UK, continental Europe and Australia. Our analysis identifies key genetic changes linked to the rapid transcontinental dissemination of epidemic C. difficile 027/BI/NAP1 and highlights the routes by which it spreads through the global healthcare system.

Agency and learning in the lifecourse: Towards an ecological perspective

Abstract: This paper is a contribution to understanding the relationship between agency and learning in the lifecourse. The contribution is mainly of a theoretical and a conceptual nature in that a particular notion of agency is used that enables agency to be conceived as something that is achieved, rather than possessed, through the active engagement of individuals with aspects of their contexts-for-action. We refer to this as an ecological understanding of agency. On the part of the actor, such engagements are characterised by particular configurations of routine, purpose and judgement. The argument is made that learning about the particular composition of one's agentic orientations and how they play out in one's life can play an important role in the achievement of agency, and that life-narratives, stories about one's life, can be an important vehicle for such learning. We explore the potential of this approach through a discussion of aspects of the learning (auto-) biographies of two participants in the...

Epigenetic Signatures of Cigarette Smoking

Abstract: Background —DNA methylation leaves a long-term signature of smoking exposure and is one potential mechanism by which tobacco exposure predisposes to adverse health outcomes, such as cancers, osteoporosis, lung, and cardiovascular disorders. Methods and Results —To comprehensively determine the association between cigarette smoking and DNA methylation, we conducted a meta-analysis of genome-wide DNA methylation assessed using the Illumina BeadChip 450K array on 15,907 blood derived DNA samples from participants in 16 cohorts (including 2,433 current, 6,518 former, and 6,956 never smokers). Comparing current versus never smokers, 2,623 CpG sites (CpGs), annotated to 1,405 genes, were statistically significantly differentially methylated at Bonferroni threshold of p<1×10-7 (18,760 CpGs at False Discovery Rate (FDR)<0.05). Genes annotated to these CpGs were enriched for associations with several smoking-related traits in genome-wide studies including pulmonary function, cancers, inflammatory diseases and heart disease. Comparing former versus never smokers, 185 of the CpGs that differed between current and never smokers were significant p<1×10-7 (2,623 CpGs at FDR<0.05), indicating a pattern of persistent altered methylation, with attenuation, after smoking cessation. Transcriptomic integration identified effects on gene expression at many differentially methylated CpGs. Conclusions —Cigarette smoking has a broad impact on genome-wide methylation that, at many loci, persists many years after smoking cessation. Many of the differentially methylated genes were novel genes with respect to biologic effects of smoking, and might represent therapeutic targets for prevention or treatment of tobacco-related diseases. Methylation at these sites could also serve as sensitive and stable biomarkers of lifetime exposure to tobacco smoke.

The Glass Cliff: Exploring the Dynamics Surrounding the Appointment of Women to Precarious Leadership Positions

Abstract: In this paper we explore the “glass cliff” form of discrimination. We review archival and experimental evidence of the glass cliff and identify multiple processes as having the potential to contribute to the phenomenon. We also outline a range of potential reactions to the phenomenon, and we elaborate strategies for eliminating glass cliffs, but, as with other forms of (gender) discrimination, we argue that these depend on the capacity for disadvantaged groups to overcome resistance on the part of those who are motivated to maintain the status quo.

Unravelling the structural and mechanistic basis of CRISPR-Cas systems.

Abstract: Bacteria and archaea have evolved sophisticated adaptive immune systems, known as CRISPR–Cas (clustered regularly interspaced short palindromic repeats–CRISPR-associated proteins) systems, which target and inactivate invading viruses and plasmids. Immunity is acquired by integrating short fragments of foreign DNA into CRISPR loci, and following transcription and processing of these loci, the CRISPR RNAs (crRNAs) guide the Cas proteins to complementary invading nucleic acid, which results in target interference. In this Review, we summarize the recent structural and biochemical insights that have been gained for the three major types of CRISPR–Cas systems, which together provide a detailed molecular understanding of the unique and conserved mechanisms of RNA-guided adaptive immunity in bacteria and archaea.