249 research outputs found
The European risk from geomagnetically induced currents (EURISGIC)
EURISGIC (www.eurisgic.eu) was the first continental-scale study of the geomagnetically induced current (GIC) hazard to Europe’s power transmission system. EURISGIC had a number of strands to it, including modelling GIC in the European system and understanding the possible extremes that the system could face. These project strands were represented by nine distinct work packages:
• The construction of the first ever European power transmission grid model and an update of the existing UK model
• The development of detailed conductivity models for Europe and, separately, the UK
• The building of geomagnetic, GIC and related science databases
• The production of a GIC risk map for Europe
• The investigation of worst case scenarios and extremes in the grid models
• The development of the NASA ‘Solar Shield’ magnetospheric and solar wind model for use in the European context
• The enhancement of a prototype GIC and geomagnetic forecast system for Europe
• The making of geomagnetic, geoelectric and GIC measurements to enhance our knowledge and validate models
• The education of the public and other stakeholders through scientific papers and other materials.
To assess and guide progress on the project a team of industry advisors was assembled. These advisors included senior power engineers from major electrical transmission system operators from across Europe, including National Grid in the UK. In this poster we demonstrate some of the major findings of the project.
The research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under grant agreement no 260330
Mycoplasma genitalium: whole genome sequence analysis, recombination and population structure.
BACKGROUND: Although Mycoplasma genitalium is a common sexually transmitted pathogen causing clinically distinct diseases both in male and females, few genomes have been sequenced up to now, due mainly to its fastidious nature and slow growth. Hence, we lack a robust phylogenetic framework to provide insights into the population structure of the species. Currently our understanding of the nature and diversity of M. genitalium relies on molecular tests targeting specific genes or regions of the genome and knowledge is limited by a general under-testing internationally. This is set against a background of drug resistance whereby M. genitalium has developed resistance to mainly all therapeutic antimicrobials. RESULTS: We sequenced 28 genomes of Mycoplasma genitalium from temporally (1980-2010) and geographically (Europe, Japan, Australia) diverse sources. All the strain showed essentially the same genomic content without any accessory regions found. However, we identified extensive recombination across their genomes with a total of 25 regions showing heightened levels of SNP density. These regions include the MgPar loci, associated with host interactions, as well as other genes that could also be involved in this role. Using these data, we generated a robust phylogeny which shows that there are two main clades with differing degrees of genomic variability. SNPs found in region V of 23S rRNA and parC were consistent with azithromycin/erythromycin and fluoroquinolone resistances, respectively, and with their phenotypic MIC data. CONCLUSIONS: The sequence data here generated is essential for designing rational approaches to type and track Mycoplasma genitalium as antibiotic resistance increases. It represents a first approach to its population genetics to better appreciate the role of this organism as a sexually transmitted pathogen
Mapping the structural path for allosteric inhibition of a short-form ATP phosphoribosyltransferase by histidine
Funding: This work was supported by a Wellcome Trust Institutional Strategic Support Fund to the University of St Andrews and the Biotechnology and Biological Sciences Research Council (BBSRC) [grant number BB/M010996/1] via an EASTBIO Doctoral Training Partnership studentship to GF. X-ray diffraction data were collected at Diamond Light Source in the UK.ATP phosphoribosyltransferase (ATPPRT) catalyses the first step of histidine biosynthesis, being allosterically inhibited by the final product of the pathway. Allosteric inhibition of long-form ATPPRTs by histidine has been extensively studied, but inhibition of short-form ATPPRTs is poorly understood. Short-form ATPPRTs are hetero-octamers formed by four catalytic subunits (HisGS) and four regulatory subunits (HisZ). HisGS alone is catalytically active and insensitive to histidine. HisZ enhances catalysis by HisGS in the absence of histidine but mediates allosteric inhibition in its presence. Here, steady-state and pre-steady-state kinetics establish that histidine is a non-competitive inhibitor of short-form ATPPRT, and that inhibition does not occur by dissociating HisGS from the hetero-octamer. The crystal structure of ATPPRT in complex with histidine and the substrate 5-phospho-α-D-ribosyl-1-pyrophosphate (PRPP) was solved, showing histidine bound solely to HisZ, with four histidine molecules per hetero-octamer. Histidine binding involves the repositioning of two HisZ loops. The histidine-binding loop moves closer to histidine to establish polar contacts. This leads to a hydrogen bond between its Tyr263 and His104 in the Asp101–Leu117 loop. The Asp101–Leu117 loop leads to the HisZ/HisGS interface, and in the absence of histidine its motion prompts HisGS conformational changes responsible for catalytic activation. Following histidine binding, interaction with the histidine-binding loop may prevent the Asp101–Leu117 loop from efficiently sampling conformations conducive to catalytic activation. Tyr263Phe-PaHisZ-containing PaATPPRT, however, is less susceptible though not insensitive to histidine inhibition, suggesting the Tyr263-His104 interaction may be relevant to, yet not solely responsible for transmission of the allosteric signal.Publisher PDFPeer reviewe
Letter to the editor : Chlamydia trachomatis samples testing falsely negative in the Aptima Combo 2 test in Finland, 2019
Non peer reviewe
Plasmid deficiency in urogenital isolates of Chlamydia trachomatis reduces infectivity and virulence in a mouse model.
We hypothesized that the plasmid of urogenital isolates of Chlamydia trachomatis would modulate infectivity and virulence in a mouse model. To test this hypothesis, we infected female mice in the respiratory or urogenital tract with graded doses of a human urogenital isolate of C. trachomatis, serovar F, possessing the cognate plasmid. For comparison, we inoculated mice with a plasmid-free serovar F isolate. Following urogenital inoculation, the plasmid-free isolate displayed significantly reduced infectivity compared with the wild-type strain with the latter yielding a 17-fold lower infectious dose to yield 50% infection. When inoculated via the respiratory tract, the plasmid-free isolate exhibited reduced infectivity and virulence (as measured by weight change) when compared to the wild-type isolate. Further, differences in infectivity, but not in virulence were observed in a C. trachomatis, serovar E isolate with a deletion within the plasmid coding sequence 1 when compared to a serovar E isolate with no mutations in the plasmid. We conclude that plasmid loss reduces virulence and infectivity in this mouse model. These findings further support a role for the chlamydial plasmid in infectivity and virulence in vivo
Sustainable urban systems: Co-design and framing for transformation
Rapid urbanisation generates risks and
opportunities for sustainable development. Urban policy
and decision makers are challenged by the complexity of
cities as social–ecological–technical systems.
Consequently there is an increasing need for
collaborative knowledge development that supports a
whole-of-system view, and transformational change at
multiple scales. Such holistic urban approaches are rare in
practice. A co-design process involving researchers,
practitioners and other stakeholders, has progressed such
an approach in the Australian context, aiming to also
contribute to international knowledge development and
sharing. This process has generated three outputs: (1) a
shared framework to support more systematic knowledge
development and use, (2) identification of barriers that
create a gap between stated urban goals and actual practice,
and (3) identification of strategic focal areas to address this
gap. Developing integrated strategies at broader urban
scales is seen as the most pressing need. The knowledge
framework adopts a systems perspective that incorporates
the many urban trade-offs and synergies revealed by a
systems view. Broader implications are drawn for policy
and decision makers, for researchers and for a shared
forward agenda
Collecting and exploiting data to understand a nation's sexual health needs: Implications for the British National Surveys of Sexual Attitudes and Lifestyles (Natsal).
No abstract available
Comprehensive global genome dynamics of Chlamydia trachomatis show ancient diversification followed by contemporary mixing and recent lineage expansion.
Chlamydia trachomatis is the world's most prevalent bacterial sexually transmitted infection and leading infectious cause of blindness, yet it is one of the least understood human pathogens, in part due to the difficulties of in vitro culturing and the lack of available tools for genetic manipulation. Genome sequencing has reinvigorated this field, shedding light on the contemporary history of this pathogen. Here, we analyze 563 full genomes, 455 of which are novel, to show that the history of the species comprises two phases, and conclude that the currently circulating lineages are the result of evolution in different genomic ecotypes. Temporal analysis indicates these lineages have recently expanded in the space of thousands of years, rather than the millions of years as previously thought, a finding that dramatically changes our understanding of this pathogen's history. Finally, at a time when almost every pathogen is becoming increasingly resistant to antimicrobials, we show that there is no evidence of circulating genomic resistance in C. trachomatis
Australia\u27s health 2000 : the seventh biennial report of the Australian Institute of Health and Welfare
Australia\u27s Health 2000 is the seventh biennial health report of the Australian Institute of Health and Welfare. It is the nation\u27s authoritative source of information on patterns of health and illness, determinants of health, the supply and use of health services, and health services costs and performance.This 2000 edition serves as a summary of Australia\u27s health record at the end of the twentieth century. In addition, a special chapter is presented on changes in Australia\u27s disease profile over the last 100 years.Australia\u27s Health 2000 is an essential reference and information source for all Australians with an interest in health
Editor's Choice - Sex Related Differences in Indication and Procedural Outcomes of Carotid interventions in VASCUNET
Objective: It has been suggested that peri-operative complications after carotid surgery may be higher in women than in men. This assumption may affect the treatment patterns, and it is thus possible that carotid endarterectomy (CEA) is provided to women less often. The aim of the current VASCUNET study was to determine sex related differences in operative risk in routine clinical practice among non-selected patients undergoing carotid revascularisation. Methods: Data on CEA and carotid artery stenting (CAS) from 14 vascular registries were collected and amalgamated. Comprehensive data were available for 223 626 carotid artery procedures; these were analysed overall and by country. The primary outcome was any stroke and or death within 30 days of carotid revascularisation. Secondary outcomes were stroke, death, or any major cardiac event or haemorrhage leading to re-operation. Results: Of the procedures, 34.8% were done in women. The proportion of CEA for asymptomatic stenosis compared with symptomatic stenosis was significantly higher among women than men (38.4% vs. 36.9%, p < .001). The proportion of octogenarians was higher among women than men who underwent CEA in both asymptomatic (21.2% vs. 19.9%) and symptomatic patients (24.3% vs. 21.4%). In the unadjusted analysis of symptomatic and asymptomatic patients, there were no significant differences between men and women in the rate of post-operative combined stroke and or death, any major cardiac event, or combined death, stroke, and any major cardiac event after CEA. Also, after stenting for asymptomatic or symptomatic carotid stenosis, there were no significant differences between men and women in the rate of post-operative complications. In adjusted analyses, sex was not significantly associated with any of the end points. Higher age and CAS vs. CEA were independently associated with all four end points. Conclusion: This study confirmed that, in a large registry among non-selected patients, no significant sex related differences were found in peri-operative complication rates after interventions for carotid stenosis
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