High-throughput analysis of Yersinia pseudotuberculosis gene essentiality in optimised in vitro conditions, and implications for the speciation of Yersinia pestis.

BACKGROUND: Yersinia pseudotuberculosis is a zoonotic pathogen, causing mild gastrointestinal infection in humans. From this comparatively benign pathogenic species emerged the highly virulent plague bacillus, Yersinia pestis, which has experienced significant genetic divergence in a relatively short time span. Much of our knowledge of Yersinia spp. evolution stems from genomic comparison and gene expression studies. Here we apply transposon-directed insertion site sequencing (TraDIS) to describe the essential gene set of Y. pseudotuberculosis IP32953 in optimised in vitro growth conditions, and contrast these with the published essential genes of Y. pestis. RESULTS: The essential genes of an organism are the core genetic elements required for basic survival processes in a given growth condition, and are therefore attractive targets for antimicrobials. One such gene we identified is yptb3665, which encodes a peptide deformylase, and here we report for the first time, the sensitivity of Y. pseudotuberculosis to actinonin, a deformylase inhibitor. Comparison of the essential genes of Y. pseudotuberculosis with those of Y. pestis revealed the genes whose importance are shared by both species, as well as genes that were differentially required for growth. In particular, we find that the two species uniquely rely upon different iron acquisition and respiratory metabolic pathways under similar in vitro conditions. CONCLUSIONS: The discovery of uniquely essential genes between the closely related Yersinia spp. represent some of the fundamental, species-defining points of divergence that arose during the evolution of Y. pestis from its ancestor. Furthermore, the shared essential genes represent ideal candidates for the development of novel antimicrobials against both species

Observations of the Optical Counterpart to XTE J1118+480 During Outburst by the ROTSE-I Telescope

The X-ray nova XTE J1118+480 exhibited two outbursts in the early part of 2000. As detected by the Rossi X-ray Timing Explorer (RXTE), the first outburst began in early January and the second began in early March. Routine imaging of the northern sky by the Robotic Optical Transient Search Experiment (ROTSE) shows the optical counterpart to XTE J1118+480 during both outbursts. These data include over 60 epochs from January to June 2000. A search of the ROTSE data archives reveal no previous optical outbursts of this source in selected data between April 1998 and January 2000. While the X-ray to optical flux ratio of XTE J1118+480 was low during both outbursts, we suggest that they were full X-ray novae and not mini-outbursts based on comparison with similar sources. The ROTSE measurements taken during the March 2000 outburst also indicate a rapid rise in the optical flux that preceded the X-ray emission measured by the RXTE by approximately 10 days. Using these results, we estimate a pre-outburst accretion disk inner truncation radius of 1.2 x 10^4 Schwarzschild radii.Comment: 9 pages, 1 table, 2 figure

Para-cresol production by Clostridium difficile affects microbial diversity and membrane integrity of Gram-negative bacteria

Clostridium difficile is a Gram-positive spore-forming anaerobe and a major cause of antibiotic-associated diarrhoea. Disruption of the commensal microbiota, such as through treatment with broad-spectrum antibiotics, is a critical precursor for colonisation by C. difficile and subsequent disease. Furthermore, failure of the gut microbiota to recover colonisation resistance can result in recurrence of infection. An unusual characteristic of C. difficile among gut bacteria is its ability to produce the bacteriostatic compound para-cresol (p-cresol) through fermentation of tyrosine. Here, we demonstrate that the ability of C. difficile to produce p-cresol in vitro provides a competitive advantage over gut bacteria including Escherichia coli, Klebsiella oxytoca and Bacteroides thetaiotaomicron. Metabolic profiling of competitive co-cultures revealed that acetate, alanine, butyrate, isobutyrate, p-cresol and p-hydroxyphenylacetate were the main metabolites responsible for differentiating the parent strain C. difficile (630Δerm) from a defined mutant deficient in p-cresol production. Moreover, we show that the p-cresol mutant displays a fitness defect in a mouse relapse model of C. difficile infection (CDI). Analysis of the microbiome from this mouse model of CDI demonstrates that colonisation by the p-cresol mutant results in a distinctly altered intestinal microbiota, and metabolic profile, with a greater representation of Gammaproteobacteria, including the Pseudomonales and Enterobacteriales. We demonstrate that Gammaproteobacteria are susceptible to exogenous p-cresol in vitro and that there is a clear divide between bacterial Phyla and their susceptibility to p-cresol. In general, Gram-negative species were relatively sensitive to p-cresol, whereas Gram-positive species were more tolerant. This study demonstrates that production of p-cresol by C. difficile has an effect on the viability of intestinal bacteria as well as the major metabolites produced in vitro. These observations are upheld in a mouse model of CDI, in which p-cresol production affects the biodiversity of gut microbiota and faecal metabolite profiles, suggesting that p-cresol production contributes to C. difficile survival and pathogenesis.Peer reviewedFinal Published versio

Implementation fidelity of a computer-assisted intervention for children with speech sound disorders

© 2017 The Speech Pathology Association of Australia Limited Published by Informa UK Limited, trading as Taylor & Francis Group. Background: Implementation fidelity refers to the degree to which an intervention or programme adheres to its original design. This paper examines implementation fidelity in the Sound Start Study, a clustered randomised controlled trial of computer-assisted support for children with speech sound disorders (SSD). Method: Sixty-three children with SSD in 19 early childhood centres received computer-assisted support (Phoneme Factory Sound Sorter [PFSS]–Australian version). Educators facilitated the delivery of PFSS targeting phonological error patterns identified by a speech-language pathologist. Implementation data were gathered via (1) the computer software, which recorded when and how much intervention was completed over 9 weeks; (2) educators’ records of practice sessions; and (3) scoring of fidelity (intervention procedure, competence and quality of delivery) from videos of intervention sessions. Result: Less than one-third of children received the prescribed number of days of intervention, while approximately one-half participated in the prescribed number of intervention plays. Computer data differed from educators’ data for total number of days and plays in which children participated; the degree of match was lower as data became more specific. Fidelity to intervention procedures, competency and quality of delivery was high. Conclusion: Implementation fidelity may impact intervention outcomes and so needs to be measured in intervention research; however, the way in which it is measured may impact on data

The Dark Side of ROTSE-III Prompt GRB Observations

We present several cases of optical observations during gamma-ray bursts (GRBs) which resulted in prompt limits but no detection of optical emission. These limits constrain the prompt optical flux densities and the optical brightness relative to the gamma-ray emission. The derived constraints fall within the range of properties observed in GRBs with prompt optical detections, though at the faint end of optical/gamma flux ratios. The presently accessible prompt optical limits do not require a different set of intrinsic or environmental GRB properties, relative to the events with prompt optical detections.Comment: ApJ accepted. 20 pages in draft manuscript form, which includes 6 pages of tables and 2 figure

The relative efficiency of automatic and discretionary regional aid

For the last two decades, the primary instruments for UK regional policy have been discretionary subsidies. Such aid is targeted at "additional" projects - projects that would not have been implemented without the subsidy - and the subsidy should be the minimum necessary for the project to proceed. Discretionary subsidies are thought to be more efficient than automatic subsidies, where many of the aided projects are non-additional and all projects receive the same subsidy rate. The present paper builds on Swales (1995) and Wren (2007a) to compare three subsidy schemes: an automatic scheme and two types of discretionary scheme, one with accurate appraisal and the other with appraisal error. These schemes are assessed on their expected welfare impacts. The particular focus is the reduction in welfare gain imposed by the interaction of appraisal error and the requirements for accountability. This is substantial and difficult to detect with conventional evaluation techniques

SDWFS-MT-1: A Self-Obscured Luminous Supernova at z~0.2

We report the discovery of a six-month-long mid-infrared transient, SDWFS-MT-1 (aka SN 2007va), in the Spitzer Deep, Wide-Field Survey of the NOAO Deep Wide-Field Survey Bootes field. The transient, located in a z=0.19 low luminosity (M_[4.5]~-18.6 mag, L/L_MilkyWay~0.01) metal-poor (12+log(O/H)~7.8) irregular galaxy, peaked at a mid-infrared absolute magnitude of M_[4.5]~-24.2 in the 4.5 micron Spitzer/IRAC band and emitted a total energy of at least 10^51 ergs. The optical emission was likely fainter than the mid-infrared, although our constraints on the optical emission are poor because the transient peaked when the source was "behind" the Sun. The Spitzer data are consistent with emission by a modified black body with a temperature of ~1350 K. We rule out a number of scenarios for the origin of the transient such as a Galactic star, AGN activity, GRB, tidal disruption of a star by a black hole and gravitational lensing. The most plausible scenario is a supernova exploding inside a massive, optically thick circumstellar medium, composed of multiple shells of previously ejected material. If the proposed scenario is correct, then a significant fraction (~10%) of the most luminous supernova may be self-enshrouded by dust not only before but also after the supernova occurs. The spectral energy distribution of the progenitor of such a supernova would be a slightly cooler version of eta Carina, peaking at 20-30 microns.Comment: 26 pages, 5 figures, 1 table, accepted for publication in Ap

Status of the ROTSE-III telescope network

ROTSE-III is a homogeneous worldwide array of 4 robotic telescopes. They were designed to provide optical observations of γ-ray burst (GRB) afterglows as close as possible to the start of γ-ray emission. ROTSE-III is fulfilling its potential for GRB science, and provides optical observations for a variety of astrophysical sources in the interim between GRB events

Dialogue and materiality/embodiment in science|arts creative pedagogy: their role and manifestation

This is the final version. Available on open access from Elsevier via the DOI in this record.This paper responds to recent calls to explore the nuances of the interaction between the sciences, the arts and their inherent creativity to better understand their potential within teaching and learning. Building on previous arguments that the science-arts-creativity relationship is dialogic and relational, this research focuses on the question: How are dialogue and material/embodied activity manifested within creative pedagogy? We begin with a fusion of Bakhtinian-inspired and New-Materialist understandings of dialogue drawing out the importance of embodiment in order to revitalize how we articulate dialogue within creative educational practice. We then take on the challenge of a materialist diffractive analysis to conduct research which complements the theoretical framing and offers our outcomes in a way that appropriately makes the phenomena tangible. We present the outcomes of the diffractive analysis including the constitution of matter as well as meaning in the dialogic space; and the emergence of new assemblages of embodied teachers, students, ideas, and objects within transdisciplinary educational practice. We conclude by arguing for the benefits of diffractive analysis: that we have fore-fronted the entangled relationality of trans-disciplinary creative pedagogy; avoided bracketing out aspects of education that are often side-lined; opened out the space of pedagogical approaches that might be attempted; and begun to challenge what education is for. In so doing, the article aims to open up new ways for teachers, students and researchers to experience seeing, doing, feeling and researching science|arts creative pedagogy and provoke conversations about how this might develop in the future.European Commissio

Separated at Birth? Microarray Analysis of Two Strikingly Similar Yersinia Species

This is the final version of the article. Available from [publisher] via the DOI in this record.--We acknowledge financial support for this project from DSTL and The Wellcome Trust. We also acknowledge BµG@S (the Bacterial Microarray Group at St George’s) and The Wellcome Trust for funding their work; Keith Vass from the University of Glasgow; and Mike Prentice from St. Bartholomew’s Hospital for his advice and expertise in all things Yersinia