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Search Results: 1 - 10 of 464219 matches for " Grant A. Hill-Cawthorne "
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The Population Structure of Vibrio cholerae from the Chandigarh Region of Northern India
Moataz Abd El Ghany ,Jagadish Chander,Ankur Mutreja,Mamoon Rashid,Grant A. Hill-Cawthorne,Shahjahan Ali,Raeece Naeem,Nicholas R. Thomson,Gordon Dougan,Arnab Pain
PLOS Neglected Tropical Diseases , 2014, DOI: 10.1371/journal.pntd.0002981
Abstract: Background Cholera infection continues to be a threat to global public health. The current cholera pandemic associated with Vibrio cholerae El Tor has now been ongoing for over half a century. Methodology/Principal Findings Thirty-eight V. cholerae El Tor isolates associated with a cholera outbreak in 2009 from the Chandigarh region of India were characterised by a combination of microbiology, molecular typing and whole-genome sequencing. The genomic analysis indicated that two clones of V. cholera circulated in the region and caused disease during this time. These clones fell into two distinct sub-clades that map independently onto wave 3 of the phylogenetic tree of seventh pandemic V. cholerae El Tor. Sequence analyses of the cholera toxin gene, the Vibrio seventh Pandemic Island II (VSPII) and SXT element correlated with this phylogenetic position of the two clades on the El Tor tree. The clade 2 isolates, characterized by a drug-resistant profile and the expression of a distinct cholera toxin, are closely related to the recent V. cholerae isolated elsewhere, including Haiti, but fell on a distinct branch of the tree, showing they were independent outbreaks. Multi-Locus Sequence Typing (MLST) distinguishes two sequence types among the 38 isolates, that did not correspond to the clades defined by whole-genome sequencing. Multi-Locus Variable-length tandem-nucleotide repeat Analysis (MLVA) identified 16 distinct clusters. Conclusions/Significance The use of whole-genome sequencing enabled the identification of two clones of V. cholerae that circulated during the 2009 Chandigarh outbreak. These clones harboured a similar structure of ICEVchHai1 but differed mainly in the structure of CTX phage and VSPII. The limited capacity of MLST and MLVA to discriminate between the clones that circulated in the 2009 Chandigarh outbreak highlights the value of whole-genome sequencing as a route to the identification of further genetic markers to subtype V. cholerae isolates.
Recombinations in Staphylococcal Cassette Chromosome mec Elements Compromise the Molecular Detection of Methicillin Resistance in Staphylococcus aureus
Grant A. Hill-Cawthorne, Lyndsey O. Hudson, Moataz Fouad Abd El Ghany, Olaf Piepenburg, Mridul Nair, Andrew Dodgson, Matthew S. Forrest, Taane G. Clark, Arnab Pain
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0101419
Abstract: Clinical laboratories are increasingly using molecular tests for methicillin-resistant Staphylococcus aureus (MRSA) screening. However, primers have to be targeted to a variable chromosomal region, the staphylococcal cassette chromosome mec (SCCmec). We initially screened 726 MRSA isolates from a single UK hospital trust by recombinase polymerase amplification (RPA), a novel, isothermal alternative to PCR. Undetected isolates were further characterised using multilocus sequence, spa typing and whole genome sequencing. 96% of our tested phenotypically MRSA isolates contained one of the six orfX-SCCmec junctions our RPA test and commercially available molecular tests target. However 30 isolates could not be detected. Sequencing of 24 of these isolates demonstrated recombinations within the SCCmec element with novel insertions that interfered with the RPA, preventing identification as MRSA. This result suggests that clinical laboratories cannot rely solely upon molecular assays to reliably detect all methicillin-resistance. The presence of significant recombinations in the SCCmec element, where the majority of assays target their primers, suggests that there will continue to be isolates that escape identification. We caution that dependence on amplification-based molecular assays will continue to result in failure to diagnose a small proportion (~4%) of MRSA isolates, unless the true level of SCCmec natural diversity is determined by whole genome sequencing of a large collection of MRSA isolates.
Comparative Genomics of the Apicomplexan Parasites Toxoplasma gondii and Neospora caninum: Coccidia Differing in Host Range and Transmission Strategy
Adam James Reid,Sarah J. Vermont,James A. Cotton,David Harris,Grant A. Hill-Cawthorne,Stephanie K?nen-Waisman,Sophia M. Latham,Tobias Mourier,Rebecca Norton,Michael A. Quail,Mandy Sanders,Dhanasekaran Shanmugam,Amandeep Sohal,James D. Wasmuth,Brian Brunk,Michael E. Grigg,Jonathan C. Howard,John Parkinson,David S. Roos,Alexander J. Trees,Matthew Berriman,Arnab Pain ,Jonathan M. Wastling
PLOS Pathogens , 2012, DOI: 10.1371/journal.ppat.1002567
Abstract: Toxoplasma gondii is a zoonotic protozoan parasite which infects nearly one third of the human population and is found in an extraordinary range of vertebrate hosts. Its epidemiology depends heavily on horizontal transmission, especially between rodents and its definitive host, the cat. Neospora caninum is a recently discovered close relative of Toxoplasma, whose definitive host is the dog. Both species are tissue-dwelling Coccidia and members of the phylum Apicomplexa; they share many common features, but Neospora neither infects humans nor shares the same wide host range as Toxoplasma, rather it shows a striking preference for highly efficient vertical transmission in cattle. These species therefore provide a remarkable opportunity to investigate mechanisms of host restriction, transmission strategies, virulence and zoonotic potential. We sequenced the genome of N. caninum and transcriptomes of the invasive stage of both species, undertaking an extensive comparative genomics and transcriptomics analysis. We estimate that these organisms diverged from their common ancestor around 28 million years ago and find that both genomes and gene expression are remarkably conserved. However, in N. caninum we identified an unexpected expansion of surface antigen gene families and the divergence of secreted virulence factors, including rhoptry kinases. Specifically we show that the rhoptry kinase ROP18 is pseudogenised in N. caninum and that, as a possible consequence, Neospora is unable to phosphorylate host immunity-related GTPases, as Toxoplasma does. This defense strategy is thought to be key to virulence in Toxoplasma. We conclude that the ecological niches occupied by these species are influenced by a relatively small number of gene products which operate at the host-parasite interface and that the dominance of vertical transmission in N. caninum may be associated with the evolution of reduced virulence in this species.
Chemical Structure Identification in Metabolomics: Computational Modeling of Experimental Features
Lochana C Menikarachchi,Mai A Hamdalla,Dennis W Hill,David F Grant
Computational and Structural Biotechnology Journal , 2013,
Abstract: The identification of compounds in complex mixtures remains challenging despite recent advances in analytical techniques. At present, no single method can detect and quantify the vast array of compounds that might be of potential interest in metabolomics studies. High performance liquid chromatography/mass spectrometry (HPLC/MS) is often considered the analytical method of choice for analysis of biofluids. The positive identification of an unknown involves matching at least two orthogonal HPLC/MS measurements (exact mass, retention index, drift time etc.) against an authentic standard. However, due to the limited availability of authentic standards, an alternative approach involves matching known and measured features of the unknown compound with computationally predicted features for a set of candidate compounds downloaded from a chemical database. Computationally predicted features include retention index, ECOM50 (energy required to decompose 50% of a selected precursor ion in a collision induced dissociation cell), drift time, whether the unknown compound is biological or synthetic and a collision induced dissociation (CID) spectrum. Computational predictions are used to filter the initial “bin” of candidate compounds. The final output is a ranked list of candidates that best match the known and measured features. In this mini review, we discuss cheminformatics methods underlying this database search-filter identification approach.
The radiative transfer of synchrotron radiation through a compressed random magnetic field
T. V. Cawthorne,P. A. Hughes
Physics , 2014, DOI: 10.1088/0004-637X/771/1/60
Abstract: This paper examines the radiative transfer of synchrotron radiation in the presence of a magnetic field configuration resulting from the compression of a highly disordered magnetic field. It is shown that, provided Faraday rotation and circular polarization can be neglected, the radiative transfer equations for synchrotron radiation separate for this configuration, and the intensities and polarization values for sources that are uniform on large scales can be found straightforwardly in the case where opacity is significant. Although the emission and absorption coefficients must, in general, be obtained numerically, the process is much simpler than a full numerical solution to the transfer equations. Some illustrative results are given and an interesting effect, whereby the polarization increases while the magnetic field distribution becomes less strongly confined to the plane of compression, is discussed. The results are of importance for the interpretation of polarization near the edges of lobes in radio galaxies and of bright features in the parsec--scale jets of AGN, where such magnetic field configurations are believed to exist. (Note: The original ApJ version of this paper contained two errata, which are corrected in this version of the paper. First, Fig. 2 was plotted as a mirror image of the correct version, reflected about the line $\log_{10}(\nu/ \nu_0)=0$. Second, as stated, Equation A16 is valid for $\gamma=2$, not $\gamma=3$.)
Impact of the Delta (1232) resonance on neutral pion photoproduction in chiral perturbation theory
Lloyd W. Cawthorne,Judith A. McGovern
Physics , 2015,
Abstract: We present an ongoing project to assess the importance of D-waves and the $\Delta (1232)$ resonance for descriptions of neutral pion photoproduction in Heavy Baryon Chiral Perturbation Theory. This research has been motivated by data published by the A2 and CB-TAPS collaborations at MAMI [1]. This data has reached unprecedented levels of accuracy from threshold through to the $\Delta$ resonance. Accompanying the experimental work, there has also been a series of publications studying the theory that show that, to go beyond an energy of $E_\gamma=170$ MeV, it is necessary to include other aspects, in particular the $\Delta (1232)$ as a degree of freedom [2] and possibly higher partial waves [3].
Polarization structure in the core of 1803+784: a signature of recollimation shocks?
T. V. Cawthorne,S. G. Jorstad,A. P. Marscher
Physics , 2013, DOI: 10.1088/0004-637X/772/1/14
Abstract: The extragalactic radio source 1803+784 is a BL Lac object that shows rapid variability and strong linear polarization. Very long baseline interferometry observations reveal that the core possesses a distinctive structure in polarized intensity with two maxima on axis and two minima symmetrically placed on either side. The approximately radial pattern of electric field polarization rods is reminiscent of the results obtained earlier by Cawthorne (2006) for conical shocks, but, individually, these do not reproduce the main features of the polarized intensity images. In numerical simulations and experiments, these shocks occur in pairs and help to stabilize jets as they adjust to changes in environment. Here, the polarization resulting from such structures is investigated using an approximate, analytical approach, by making some simple assumptions about the nature of the flow between two such shock waves. For fairly small viewing angles, it is found that a reasonable representation of the core polarization of 1803+784 can be obtained. The similarity between the observed and model polarization supports the view that the core structure in 1803+784 represents a recollimation shock, and that such shock waves may be responsible for the first disturbance and hence brightening of the quiescent flow in astrophysical jets.
Analysis of 6cm VLBI polarization observations of a complete sample of northern BL Lacertae Objects
D. C. Gabuzda,A. B. Pushkarev,T. V. Cawthorne
Physics , 2003, DOI: 10.1046/j.1365-8711.2000.03932.x
Abstract: The results of VLBI total intensity (I) and linear polarization (P) observations at 6cm are presented for ten radio bright BL Lacertae objects. These images complete first-epoch polarization observations for the 1-Jy sample of northern BL Lacertae objects defined by Kuhr and Schmidt. Estimates of superluminal speeds are presented for several sources, bringing the total number of sources in the sample for which such estimates are available to 16. Second epoch observations currently being reduced should yield speed estimates for VLBI features in essentially all the sources in the sample. The jet magnetic fields of these BL Lacertae objects are usually transverse to the local jet direction, but a sizeable minority (about 30%) have VLBI jet components with longitudinal magnetic fields. This may suggest that the conditions in the VLBI jets of BL Lacertae objects are favorable for the formation of relativistic shocks; alternatively, it may be that the toroidal component of the intrinsic jet magnetic field is characteristically dominant in these sources.
Impact of Sequence Non-Identities on Recombination within the pil System of Neisseria gonorrhoeae  [PDF]
Stuart A. Hill, Jenny Wachter
Open Journal of Genetics (OJGen) , 2014, DOI: 10.4236/ojgen.2014.43023

Neisseria gonorrhoeae engages in extensive intra-cellular gene conversion between the PilE-expression locus (pilE) and the transcriptionally-silent pil gene copies (pilS). In silico analyses were applied to investigate the extent of sequence heterogeneity between the various pilS gene copies. Analysis of synonymous and non-synonymous substitutions between the different pilS genes indicated that relatively few amino acid changes would occur due to nucleotide polymorphisms towards the 5’ end of the pilS genes whereas more frequent amino acid substitutions would be incorporated within the “hypervariable” region. The lack of non-synonymous substitutions at the 5’ end of the genes was found to be under selective pressure as indicated by a positive DT score utilizing the Tajima test. The presence or absence of mismatch repair appeared to only impact recombination when non-identical DNAs recombined via the DNA transformation route, where small pil sequence heterogeneities were sufficient to terminate recombination tracts, with these sequence constraints being relieved in cells carrying a mutS mutation. Therefore, the data indicate that the effect of sequence heterogeneity on recombination within the pil

A Typology of Indigenous Engagement in Australian Environmental Management: Implications for Knowledge Integration and Social-ecological System Sustainability
Rosemary Hill,Chrissy Grant,Melissa George,Catherine J. Robinson
Ecology and Society , 2012, DOI: 10.5751/es-04587-170123
Abstract: Indigenous peoples now engage with many decentralized approaches to environmental management that offer opportunities for integration of Indigenous Ecological Knowledge (IEK) and western science to promote cultural diversity in the management of social-ecological system sustainability. Nevertheless, processes of combining IEK with western science are diverse and affected by numerous factors, including the adaptive co-management context, the intrinsic characteristics of the natural resources, and the governance systems. We present a typology of Indigenous engagement in environmental management, derived through comparative analysis of 21 Australian case studies, and consider its implications for the integration of IEK with western science. Sociological and rational choice institutionalism underpin our analytical framework, which differentiates on three axes: (1) power sharing, incorporating decision making, rules definition, resource values and property rights; (2) participation, incorporating participatory processes, organizations engaged, and coordination approaches; (3) intercultural purpose, incorporating purposes of environmental management, Indigenous engagement, Indigenous development and capacity building. Our typology groups engagement into four types: Indigenous governed collaborations; Indigenous-driven co-governance; agency-driven co-governance; and agency governance. From our analysis of manifestations of knowledge integration across the types, we argue that Indigenous governance and Indigenous-driven co-governance provides better prospects for integration of IEK and western science for sustainability of social-ecological systems. Supporting Indigenous governance without, or with only a limited requirement for power sharing with other agencies sustains the distinct Indigenous cultural purposes underpinning IEK, and benefits knowledge integration. We conclude by advocating that the typology be applied to test its general effectiveness in guiding practitioners and researchers to develop robust governance for Indigenous knowledge integration in environmental management.
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