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Search Results: 1 - 10 of 403404 matches for " Kate M Peters "
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A Single Acidic Residue Can Guide Binding Site Selection but Does Not Govern QacR Cationic-Drug Affinity
Kate M. Peters,Benjamin E. Brooks,Maria A. Schumacher,Ronald A. Skurray,Richard G. Brennan,Melissa H. Brown
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0015974
Abstract: Structures of the multidrug-binding repressor protein QacR with monovalent and bivalent cationic drugs revealed that the carboxylate side-chains of E90 and E120 were proximal to the positively charged nitrogens of the ligands ethidium, malachite green and rhodamine 6G, and therefore may contribute to drug neutralization and binding affinity. Here, we report structural, biochemical and in vivo effects of substituting these glutamate residues. Unexpectedly, substitutions had little impact on ligand affinity or in vivo induction capabilities. Structures of QacR(E90Q) and QacR(E120Q) with ethidium or malachite green took similar global conformations that differed significantly from all previously described QacR-drug complexes but still prohibited binding to cognate DNA. Strikingly, the QacR(E90Q)-rhodamine 6G complex revealed two mutually exclusive rhodamine 6G binding sites. Despite multiple structural changes, all drug binding was essentially isoenergetic. Thus, these data strongly suggest that rather than contributing significantly to ligand binding affinity, the role of acidic residues lining the QacR multidrug-binding pocket is primarily to attract and guide cationic drugs to the “best available” positions within the pocket that elicit QacR induction.
The Serum Resistome of a Globally Disseminated Multidrug Resistant Uropathogenic Escherichia coli Clone
Minh-Duy Phan,Kate M. Peters,Sohinee Sarkar,Samuel W. Lukowski,Luke P. Allsopp,Danilo Gomes Moriel,Maud E. S. Achard,Makrina Totsika,Vikki M. Marshall,Mathew Upton,Scott A. Beatson,Mark A. Schembri
PLOS Genetics , 2013, DOI: 10.1371/journal.pgen.1003834
Abstract: Escherichia coli ST131 is a globally disseminated, multidrug resistant clone responsible for a high proportion of urinary tract and bloodstream infections. The rapid emergence and successful spread of E. coli ST131 is strongly associated with antibiotic resistance; however, this phenotype alone is unlikely to explain its dominance amongst multidrug resistant uropathogens circulating worldwide in hospitals and the community. Thus, a greater understanding of the molecular mechanisms that underpin the fitness of E. coli ST131 is required. In this study, we employed hyper-saturated transposon mutagenesis in combination with multiplexed transposon directed insertion-site sequencing to define the essential genes required for in vitro growth and the serum resistome (i.e. genes required for resistance to human serum) of E. coli EC958, a representative of the predominant E. coli ST131 clonal lineage. We identified 315 essential genes in E. coli EC958, 231 (73%) of which were also essential in E. coli K-12. The serum resistome comprised 56 genes, the majority of which encode membrane proteins or factors involved in lipopolysaccharide (LPS) biosynthesis. Targeted mutagenesis confirmed a role in serum resistance for 46 (82%) of these genes. The murein lipoprotein Lpp, along with two lipid A-core biosynthesis enzymes WaaP and WaaG, were most strongly associated with serum resistance. While LPS was the main resistance mechanism defined for E. coli EC958 in serum, the enterobacterial common antigen and colanic acid also impacted on this phenotype. Our analysis also identified a novel function for two genes, hyxA and hyxR, as minor regulators of O-antigen chain length. This study offers novel insight into the genetic make-up of E. coli ST131, and provides a framework for future research on E. coli and other Gram-negative pathogens to define their essential gene repertoire and to dissect the molecular mechanisms that enable them to survive in the bloodstream and cause disease.
Androgen receptor expression predicts breast cancer survival: the role of genetic and epigenetic events
Kate M Peters, Stacey L Edwards, Shalima S Nair, Juliet D French, Peter J Bailey, Kathryn Salkield, Sandra Stein, Sarah Wagner, Glenn D Francis, Susan J Clark, Melissa A Brown
BMC Cancer , 2012, DOI: 10.1186/1471-2407-12-132
Abstract: The levels of Androgen receptor protein in a cohort of breast tumour samples was determined by immunohistochemistry and the results were compared with clinical characteristics, including survival. The role of defects in the regulation of Androgen receptor gene expression were examined by mutation and methylation screening of the 5' end of the gene, reporter assays of the 5' and 3' end of the AR gene, and searching for miRNAs that may regulate AR gene expression.AR was expressed in 56% of tumours and expression was significantly inversely associated with 10-year survival (P = 0.004). An investigation into the mechanisms responsible for the loss of AR expression revealed that hypermethylation of the AR promoter is associated with loss of AR expression in breast cancer cells but not in primary breast tumours. In AR negative breast tumours, mutation screening identified the same mutation (T105A) in the 5'UTR of two AR negative breast cancer patients but not reported in the normal human population. Reporter assay analysis of this mutation however found no evidence for a negative impact on AR 5'UTR activity. The role of miR-124 in regulating AR expression was also investigated, however no evidence for this was found.This study highlights the potential for AR expression to be an informative biomarker for breast cancer survival and sets the scene for a more comprehensive investigation of the molecular basis of this phenomenon.Breast cancer is a heterogeneous disease comprising tumour subtypes associated with variable clinical characteristics [1]. Variables including tumour size, histological subtype and grade, lymph node status and the expression of estrogen receptor alpha (ERα), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) currently assist routine clinical management [2]. However, these factors are limited in their ability to predict individual survival and response to therapy [2]. This is particularly apparent for patients with advanced b
F9 Fimbriae of Uropathogenic Escherichia coli Are Expressed at Low Temperature and Recognise Galβ1-3GlcNAc-Containing Glycans
Dani?l J. Wurpel, Makrina Totsika, Luke P. Allsopp, Lauren E. Hartley-Tassell, Christopher J. Day, Kate M. Peters, Sohinee Sarkar, Glen C. Ulett, Ji Yang, Joe Tiralongo, Richard A. Strugnell, Michael P. Jennings, Mark A. Schembri
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0093177
Abstract: Uropathogenic Escherichia coli (UPEC) is the leading causative agent of urinary tract infections (UTI) in the developed world. Among the major virulence factors of UPEC, surface expressed adhesins mediate attachment and tissue tropism. UPEC strains typically possess a range of adhesins, with type 1 fimbriae and P fimbriae of the chaperone-usher class the best characterised. We previously identified and characterised F9 as a new chaperone-usher fimbrial type that mediates biofilm formation. However, the regulation and specific role of F9 fimbriae remained to be determined in the context of wild-type clinical UPEC strains. In this study we have assessed the distribution and genetic context of the f9 operon among diverse E. coli lineages and pathotypes and demonstrated that f9 genes are significantly more conserved in a UPEC strain collection in comparison to the well-defined E. coli reference (ECOR) collection. In the prototypic UPEC strain CFT073, the global regulator protein H-NS was identified as a transcriptional repressor of f9 gene expression at 37°C through its ability to bind directly to the f9 promoter region. F9 fimbriae expression was demonstrated at 20°C, representing the first evidence of functional F9 fimbriae expression by wild-type E. coli. Finally, glycan array analysis demonstrated that F9 fimbriae recognise and bind to terminal Galβ1-3GlcNAc structures.
Marriage and Psychological Wellbeing: The Role of Social Support  [PDF]
Laura K. Soulsby, Kate M. Bennett
Psychology (PSYCH) , 2015, DOI: 10.4236/psych.2015.611132
Abstract: The married consistently report better levels of psychological health compared to the unmarried. Using a cross-sectional questionnaire design, this research examines to what extent this relationship between marital status and psychological wellbeing can be explained by perceived social support. The data reveal that, after controlling for demographic variables, number of daily hassles and coping strategies, widowed and divorced adults report significantly poorer psychological health compared to those who remain married. Moreover, while there was limited evidence that perceived social support moderates the association between marital status and psychological wellbeing, perceived social support did emerge as a significant mediator of this relationship. Perceived social support explained the influence of being widowed, divorced and never married on psychological wellbeing, such that lower levels of support in these groups resulted in poorer psychological health. Thus, social support may be an important variable for interventions to minimize the negative consequences of a transition out of marriage.
Extending conceptual frameworks: life course epidemiology for the study of back pain
Kate M Dunn
BMC Musculoskeletal Disorders , 2010, DOI: 10.1186/1471-2474-11-23
Abstract: Life course concepts can be divided into three categories. Concept 1: patterns over time, risk chains and accumulation. Simple 'chains of risk' have been studied - e.g. depression leading to back pain - but studies involving more risk factors in the chain are infrequent. Also, we have not examined how risk accumulation influences outcome, e.g. whether multiple episodes or duration of depression, throughout the life course, better predicts back pain. One-year back pain trajectories have been described, and show advantages for studying back pain, but there are few descriptions of longer-term patterns with associated transitions and turning points. Concept 2: influences and determinants of pathways. Analyses in back pain studies commonly adjust associations for potential confounders, but specific analysis of factors modifying risk, or related to the resilience or susceptibility to back pain, are rarely studied. Concept 3: timing of risk. Studies of critical or sensitive periods - crucial times of life which influence health later in life - are scarce in back pain research. Such analyses could help identify factors that influence the experience of pain throughout the life course.Back pain researchers could usefully develop hypotheses and models of how risks from different stages of life might interact and influence the onset, persistence and prognosis of back pain throughout the life course. Adoption of concepts and methods from life course epidemiology could facilitate this.Studies of back pain were historically based in the biomedical model of disease and illness, where symptoms were assumed to signify underlying diseases with known aetiology (e.g. injury caused by lifting), clear-cut pathology (e.g. prolapsed disc) and specific treatment (e.g. surgery). Many researchers have, more recently, embraced the biopsychosocial model, first described 30 years ago by Engel [1], which emphasizes the inter-relationships between biological, psychological and social factors [2]. C
The Concordance Genus of 11--Crossing Knots
M. Kate Kearney
Mathematics , 2012,
Abstract: The concordance genus of a knot is the least genus of any knot in its concordance class. It is bounded above by the genus of the knot, and bounded below by the slice genus, two well-studied invariants. In this paper we consider the concordance genus of 11--crossing prime knots. This analysis resolves the concordance genus of 533 of the 552 prime 11--crossing knots. The appendix to the paper gives concordance diagrams for 59 knots found to be concordant to knots of lower genus, including null-concordances for the 30 11--crossing knots known to be slice.
The Stable Concordance Genus
M. Kate Kearney
Mathematics , 2013,
Abstract: The concordance genus of a knot is the least genus of any knot in its concordance class. Although difficult to compute, it is a useful invariant that highlights the distinction between the three-genus and four-genus. In this paper we define and discuss the stable concordance genus of a knot, which describes the behavior of the concordance genus under connected sum.
Combustion Modeling with the G-Equation Modélisation de la combustion avec l'équation de G
Peters N.,Dekena M.
Oil & Gas Science and Technology , 2006, DOI: 10.2516/ogst:1999024
Abstract: Numerical investigations concerning the turbulent flame front propagation in Gasoline Direct Injection (GDI) engines were made by implementing a flamelet model in the CFD code Fire. The advantage of this combustion model is the decoupling of the chemistry from the turbulent flow. For this purpose the combustion chamber has to be divided into a burned and an unburned area, which is realized by transporting a scalar field (G-Equation). The reference value defines the present averaged flame position. The complete reaction kinetics is calculated interactively with the CFD code in a one dimensional Representative Interactive Flamelet (RIF) code. This combustion model was verified by simulating a 2. 0 l-2 V gasoline engine with homogeneous combustion where a parameter study was conducted to check the flamelet model for plausibility. Finally, the potential of this combustion model was investigated by simulating a hypothetical 2. 0 1-4 V GDI engine. Une investigation numérique relative à la propagation des fronts de flammes turbulents dans les moteurs à essence à injection directe (GDI) a été menée en implantant un modèle de flameletdans le code 3D Fire. L'avantage de ce modèle de combustion est de découpler la chimie de l'écoulement turbulent en divisant la chambre de combustion en deux zones : br lée et imbr lée, à l'aide d'une équation de transport d'un scalaire (équation de G). Une valeur de référence de ce scalaire définit la position moyenne de la flamme. Une chimie complète est calculée interactivement avec le calcul 3D à l'aide d'un code monodimensionnel RIF (Representative Interactive Flamelet). Le modèle de combustion a été validé sur la simulation d'un moteur 2 litres à 2 soupapes en combustion homogène pour vérifier la représentativité de l'approche flamelet . Puis, le potentiel du modèle de combustion a été étudié en simulant un moteur modèle 2 litres 4 soupapes GDI.
Foundation degrees: the way forward for ICT in HE – a call for debate on the design, implementation and delivery of ICT foundation degrees
M. D. Peters
ITALICS , 2005,
Abstract: This paper is written to promote debate between those UK consortia who are delivering Foundation Degree programmes in Information and Communication Technologies. It takes as a reference point the Foundation Degree (final draft) benchmark statement issued by the Qualifications Assurance Agency and poses questions about various aspects of this qualification which the author believes will be problematic. It discusses work based learning from both the institutional and practitioner’s viewpoint, the idea of flexible modes of delivery which fit in with the widening participation agenda, ways of making the qualification attractive to employers and potential students, and finally, progression to higher qualifications. It does not offer solutions to any of the problems: but signposts research being undertaken by the author in conjunction with the Higher Education Academy.
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