40 research outputs found
Leaders and laggards in the pursuit of an EU just transition
The just transition from coal, oil, and gas to renewable energy sources involves commitment from all EU states. But who is leading, or lagging? We apply an innovative DeePeR framework to identify these states, using open-access quantitative global data from multiple sources, by evaluating the energy and equity dimensions of Distributive, Procedural and Restorative justice. Using rank percentile scores, we assessed EU nations\u27 level of fossil fuel dependency (including both energy and financial dependency) and distributional inequality, their fossil fuel CO2 emissions, climate finance pledges and a calculated procedural justice score, and their commitment to modern renewable electricity output and rankings on fair and renewable jobs. We find that EU states\u27 performances on just transition are distinct across four broad regions; Scandinavia, eastern Europe, western Europe, and the Mediterranean. We discuss the nuances of fossil fuel embeddedness in the EU. This is followed by reflection on the importance of embedding fairness in the deployment of new renewable jobs. Finally, we consider the implications for a better-targeted financial mechanism for just transition alongside a fossil fuel divestment strategy
Identifying, improving, and investing in national commitments to just transition:reflections from Latin America and the Caribbean
A 1.5 °C world relies on the development of modern renewable energy sources in Latin America and the Caribbean. Whilst existing research offers insights into national case studies, our study responds to a lack of region-wide analysis. To identify the relative level of national commitment to a just transition in the region, this study collects, analyses, and visualizes global data from eight different sources. It uses a ranking method to analyse relative performance. To find where policy improvement is most urgently needed, trends are extrapolated on fossil fuel dependency, subsidies, and carbon dioxide emissions, as well as renewable energy production and international finance, through the lens of distributional, procedural, and restorative justice. We call for a new approach to international clean energy finance which promotes greater procedural justice whilst ensuring that green energy deployment leads to higher levels of meaningful employment
Clinical Perspectives in Integrating Whole Genome Sequencing into the Investigation of Healthcare and Public Health Outbreaks - Hype or Help?
Bioinformatics and Computational Biology analyses were supported by the University of St Andrews Bioinformatics Unit which is funded by a Wellcome Trust ISSF award [grant 097831/Z/11/Z]. The SHAIPI consortium is funded by the Chief Scientist Office through the Scottish Infection Research Network (SIRN10).Outbreaks pose a significant patient safety risk as well as being costly and time consuming to investigate. The implementation of targeted infection prevention and control (IPC) measures relies on infection prevention and control teams (IPCTs) having access to rapid results that accurately detect resistance, and typing results that give clinically useful information on the relatedness of isolates. At present, determining whether transmission has occurred can be a major challenge. Conventional typing results do not always have sufficient granularity or robustness to unequivocally define strains, and sufficient epidemiological data to establish links between patients and the environment is not always available. Whole genome sequencing (WGS) has emerged as the ultimate genotyping tool, but has not yet fully crossed the divide between research method and routine clinical diagnostic microbiology technique. A clinical WGS service was officially established in 2014 as part of the Scottish Healthcare Associated Infection Prevention Institute (SHAIPI) to confirm or refute outbreaks in hospital settings from across Scotland. In this personal view we describe our experiences that we believe provide new insights into the practical application of the use of WGS to investigate healthcare and public health outbreaks. We also propose solutions to overcome barriers to implementation of this technology in a clinical environment.Publisher PDFPeer reviewe
The handedness-associated PCSK6 locus spans an intronic promoter regulating novel transcripts
We recently reported the association of the PCSK6 gene with handedness through a quantitative genome-wide association study (GWAS; P < 0.5 × 10(-8)) for a relative hand skill measure in individuals with dyslexia. PCSK6 activates Nodal, a morphogen involved in regulating left-right body axis determination. Therefore, the GWAS data suggest that the biology underlying the patterning of structural asymmetries may also contribute to behavioural laterality, e.g. handedness. The association is further supported by an independent study reporting a variable number tandem repeat (VNTR) within the same PCSK6 locus to be associated with degree of handedness in a general population cohort. Here, we have conducted a functional analysis of the PCSK6 locus combining further genetic analysis, in silico predictions and molecular assays. We have shown that the previous GWAS signal was not tagging a VNTR effect, suggesting that the two markers have independent effects. We demonstrated experimentally that one of the top GWAS-associated markers, rs11855145, directly alters the binding site for a nuclear factor. Furthermore, we have shown that the predicted regulatory region adjacent to rs11855415 acts as a bidirectional promoter controlling the expression of novel RNA transcripts. These include both an antisense long non-coding RNA (lncRNA) and a short PCSK6 isoform predicted to be coding. This is the first molecular characterization of a handedness-associated locus that supports the role of common variants in non-coding sequences in influencing complex phenotypes through gene expression regulation
The Microevolution and Epidemiology of Staphylococcus aureus Colonization during Atopic Eczema Disease Flare.
Staphylococcus aureus is an opportunistic pathogen and variable component of the human microbiota. A characteristic of atopic eczema (AE) is colonization by S. aureus, with exacerbations associated with an increased bacterial burden of the organism. Despite this, the origins and genetic diversity of S. aureus colonizing individual patients during AE disease flares is poorly understood. To examine the microevolution of S. aureus colonization, we deep sequenced S. aureus populations from nine children with moderate to severe AE and 18 non-atopic children asymptomatically carrying S. aureus nasally. Colonization by clonal S. aureus populations was observed in both AE patients and control participants, with all but one of the individuals carrying colonies belonging to a single sequence type. Phylogenetic analysis showed that disease flares were associated with the clonal expansion of the S. aureus population, occurring over a period of weeks to months. There was a significant difference in the genetic backgrounds of S. aureus colonizing AE cases versus controls (Fisher exact test, P = 0.03). Examination of intra-host genetic heterogeneity of the colonizing S. aureus populations identified evidence of within-host selection in the AE patients, with AE variants being potentially selectively advantageous for intracellular persistence and treatment resistance.CPH was supported by Wellcome Trust (grant number 104241/z/14/z). MTGH, KAP, and KO were supported by the Scottish Infection Research Network and Chief Scientist Office through the Scottish Healthcare Associated Infection Prevention Institute consortium funding (CSO reference: SIRN10). Bioinformatics and computational biology analyses were supported by the University of St Andrews Bioinformatics Unit that is funded by a Wellcome Trust ISSF award (grant 097831/Z/11/Z). JP and MTGH were supported by Wellcome Trust grant 098051. AEM is supported by Biotechnology and Biological Sciences Research Council grant BB/M014088/1. SJB is supported by a Wellcome Trust Senior Research Fellowship in Clinical Science (106865/Z/15/Z)
Presence of optrA-mediated linezolid resistance in multiple lineages and plasmids of Enterococcus faecalis revealed by long read sequencing
Funding: This work was supported by the Chief Scientist Office (Scotland) through the Scottish Healthcare Associated Infection Prevention Institute (Reference SIRN/10). Bioinformatics and Computational Biology analyses were supported by the University of St Andrews Bioinformatics Unit, which is funded by a Wellcome Trust ISSF award [grant 105621/Z/14/Z].Transferable linezolid resistance due to optrA, poxtA, cfr and cfr-like genes is increasingly detected in enterococci associated with animals and humans globally. We aimed to characterize the genetic environment of optrA in linezolid-resistant Enterococcus faecalis isolates from Scotland. Six linezolid-resistant E. faecalis isolated from urogenital samples were confirmed to carry the optrA gene by PCR. Short read (Illumina) sequencing showed the isolates were genetically distinct (>13900 core SNPs) and belonged to different MLST sequence types. Plasmid contents were examined using hybrid assembly of short and long read (Oxford Nanopore MinION) sequencing technologies. The optrA gene was located on distinct plasmids in each isolate, suggesting that transfer of a single plasmid did not contribute to optrA dissemination in this collection. pTM6294-2, BX5936-1 and pWE0438-1 were similar to optrA-positive plasmids from China and Japan, while the remaining three plasmids had limited similarity to other published examples. We identified the novel Tn6993 transposon in pWE0254-1 carrying linezolid (optrA), macrolide (ermB) and spectinomycin [ANT(9)-Ia] resistance genes. OptrA amino acid sequences differed by 0–20 residues. We report multiple variants of optrA on distinct plasmids in diverse strains of E. faecalis . It is important to identify the selection pressures driving the emergence and maintenance of resistance against linezolid to retain the clinical utility of this antibiotic.Publisher PDFPeer reviewe
The genus Serratia revisited by genomics
The genus Serratia has been studied for over a century and includes clinically-important and diverse environmental members. Despite this, there is a paucity of genomic information across the genus and a robust whole genome-based phylogenetic framework is lacking. Here, we have assembled and analysed a representative set of 664 genomes from across the genus, including 215 historic isolates originally used in defining the genus. Phylogenomic analysis of the genus reveals a clearly-defined population structure which displays deep divisions and aligns with ecological niche, as well as striking congruence between historical biochemical phenotyping data and contemporary genomics data. We highlight the genomic, phenotypic and plasmid diversity of Serratia, and provide evidence of different patterns of gene flow across the genus. Our work provides a framework for understanding the emergence of clinical and other lineages of Serratia
Further evidence for a parent-of-origin effect at the NOP9 locus on language-related phenotypes
Background - Specific language impairment (SLI) is a common neurodevelopmental disorder, observed in 5–10 % of children. Family and twin studies suggest a strong genetic component, but relatively few candidate genes have been reported to date. A recent genome-wide association study (GWAS) described the first statistically significant association specifically for a SLI cohort between a missense variant (rs4280164) in the NOP9 gene and language-related phenotypes under a parent-of-origin model. Replications of these findings are particularly challenging because the availability of parental DNA is required. Methods - We used two independent family-based cohorts characterised with reading- and language-related traits: a longitudinal cohort (n = 106 informative families) including children with language and reading difficulties and a nuclear family cohort (n = 264 families) selected for dyslexia. Results - We observed association with language-related measures when modelling for parent-of-origin effects at the NOP9 locus in both cohorts: minimum P = 0.001 for phonological awareness with a paternal effect in the first cohort and minimum P = 0.0004 for irregular word reading with a maternal effect in the second cohort. Allelic and parental trends were not consistent when compared to the original study. Conclusions - A parent-of-origin effect at this locus was detected in both cohorts, albeit with different trends. These findings contribute in interpreting the original GWAS report and support further investigations of the NOP9 locus and its role in language-related traits. A systematic evaluation of parent-of-origin effects in genetic association studies has the potential to reveal novel mechanisms underlying complex traits
Fine mapping the KLK3 locus on chromosome 19q13.33 associated with prostate cancer susceptibility and PSA levels
Measurements of serum prostate-specific antigen (PSA) protein levels form the basis for a widely used test to screen men for prostate cancer. Germline variants in the gene that encodes the PSA protein (KLK3) have been shown to be associated with both serum PSA levels and prostate cancer. Based on a resequencing analysis of a 56 kb region on chromosome 19q13.33, centered on the KLK3 gene, we fine mapped this locus by genotyping tag SNPs in 3,522 prostate cancer cases and 3,338 controls from five case–control studies. We did not observe a strong association with the KLK3 variant, reported in previous studies to confer risk for prostate cancer (rs2735839; P = 0.20) but did observe three highly correlated SNPs (rs17632542, rs62113212 and rs62113214) associated with prostate cancer [P = 3.41 × 10−4, per-allele trend odds ratio (OR) = 0.77, 95% CI = 0.67–0.89]. The signal was apparent only for nonaggressive prostate cancer cases with Gleason score <7 and disease stage <III (P = 4.72 × 10−5, per-allele trend OR = 0.68, 95% CI = 0.57–0.82) and not for advanced cases with Gleason score >8 or stage ≥III (P = 0.31, per-allele trend OR = 1.12, 95% CI = 0.90–1.40). One of the three highly correlated SNPs, rs17632542, introduces a non-synonymous amino acid change in the KLK3 protein with a predicted benign or neutral functional impact. Baseline PSA levels were 43.7% higher in control subjects with no minor alleles (1.61 ng/ml, 95% CI = 1.49–1.72) than in those with one or more minor alleles at any one of the three SNPs (1.12 ng/ml, 95% CI = 0.96–1.28) (P = 9.70 × 10−5). Together our results suggest that germline KLK3 variants could influence the diagnosis of nonaggressive prostate cancer by influencing the likelihood of biopsy