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Search Results: 1 - 10 of 220816 matches for " Fiona C. McKay "
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IL7Rα Expression and Upregulation by IFNβ in Dendritic Cell Subsets Is Haplotype-Dependent
Fiona C. McKay, Edwin Hoe, Grant Parnell, Prudence Gatt, Stephen D. Schibeci, Graeme J. Stewart, David R. Booth
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0077508
Abstract: The IL7Rα gene is unequivocally associated with susceptibility to multiple sclerosis (MS). Haplotype 2 (Hap 2) confers protection from MS, and T cells and dendritic cells (DCs) of Hap 2 exhibit reduced splicing of exon 6, resulting in production of relatively less soluble receptor, and potentially more response to ligand. We have previously shown in CD4 T cells that IL7Rα haplotypes 1 and 2, but not 4, respond to interferon beta (IFNβ), the most commonly used immunomodulatory drug in MS, and that haplotype 4 (Hap 4) homozygotes have the highest risk of developing MS. We now show that IL7R expression increases in myeloid cells in response to IFNβ, but that the response is haplotype-dependent, with cells from homozygotes for Hap 4 again showing no response. This was shown using freshly derived monocytes, in vitro cultured immature and mature monocyte-derived dendritic cells, and by comparing homozygotes for the common haplotypes, and relative expression of alleles in heterozygotes (Hap 4 vs not Hap 4). As for T cells, in all myeloid cell subsets examined, Hap 2 homozygotes showed a trend for reduced splicing of exon 6 compared to the other haplotypes, significantly so in most conditions. These data are consistent with increased signaling being protective from MS, constitutively and in response to IFNβ. We also demonstrate significant regulation of immune response, chemokine activity and cytokine biosynthesis pathways by IL7Rα signaling in IFNβ -treated myeloid subsets. IFNβ-responsive genes are over-represented amongst genes associated with MS susceptibility. IL7Rα haplotype may contribute to MS susceptibility through reduced capacity for IL7Rα signalling in myeloid cells, especially in the presence of IFNβ, and is currently under investigation as a predictor of therapeutic response.
Degree sequences of random digraphs and bipartite graphs
Brendan D. McKay,Fiona Skerman
Mathematics , 2013,
Abstract: We investigate the joint distribution of the vertex degrees in three models of random bipartite graphs. Namely, we can choose each edge with a specified probability, choose a specified number of edges, or specify the vertex degrees in one of the two colour classes. This problem can alternatively be described in terms of the row and sum columns of random binary matrix or the in-degrees and out-degrees of a random digraph, in which case we can optionally forbid loops. It can also be cast as a problem in random hypergraphs, or as a classical occupancy, allocation, or coupon collection problem. In each case, provided the two colour classes are not too different in size nor the number of edges too low, we define a probability space based on independent binomial variables and show that its probability masses asymptotically equal those of the degrees in the graph model almost everywhere. The accuracy is sufficient to asymptotically determine the expectation of any joint function of the degrees whose maximum is at most polynomially greater than its expectation.
Novel Approaches to Detect Serum Biomarkers for Clinical Response to Interferon-β Treatment in Multiple Sclerosis
Kaushal S. Gandhi,Fiona C. McKay,Eve Diefenbach,Ben Crossett,Stephen D. Schibeci,Robert N. Heard,Graeme J. Stewart,David R. Booth,Jonathan W. Arthur
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0010484
Abstract: Interferon beta (IFNβ) is the most common immunomodulatory treatment for relapsing-remitting multiple sclerosis (RRMS). However, some patients fail to respond to treatment. In this study, we identified putative clinical response markers in the serum and plasma of people with multiple sclerosis (MS) treated with IFNβ. In a discovery-driven approach, we use 2D-difference gel electrophoresis (DIGE) to identify putative clinical response markers and apply power calculations to identify the sample size required to further validate those markers. In the process we have optimized a DIGE protocol for plasma to obtain cost effective and high resolution gels for effective spot comparison. APOA1, A2M, and FIBB were identified as putative clinical response markers. Power calculations showed that the current DIGE experiment requires a minimum of 10 samples from each group to be confident of 1.5 fold difference at the p<0.05 significance level. In a complementary targeted approach, Cytometric Beadarray (CBA) analysis showed no significant difference in the serum concentration of IL-6, IL-8, MIG, Eotaxin, IP-10, MCP-1, and MIP-1α, between clinical responders and non-responders, despite the association of these proteins with IFNβ treatment in MS.
A Transcription Factor Map as Revealed by a Genome-Wide Gene Expression Analysis of Whole-Blood mRNA Transcriptome in Multiple Sclerosis
Carlos Riveros,Drew Mellor,Kaushal S. Gandhi,Fiona C. McKay,Mathew B. Cox,Regina Berretta,S. Yahya Vaezpour,Mario Inostroza-Ponta,Simon A. Broadley,Robert N. Heard,Stephen Vucic,Graeme J. Stewart,David W. Williams,Rodney J. Scott,Jeanette Lechner-Scott,David R. Booth,Pablo Moscato
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0014176
Abstract: Several lines of evidence suggest that transcription factors are involved in the pathogenesis of Multiple Sclerosis (MS) but complete mapping of the whole network has been elusive. One of the reasons is that there are several clinical subtypes of MS and transcription factors that may be involved in one subtype may not be in others. We investigate the possibility that this network could be mapped using microarray technologies and contemporary bioinformatics methods on a dataset derived from whole blood in 99 untreated MS patients (36 Relapse Remitting MS, 43 Primary Progressive MS, and 20 Secondary Progressive MS) and 45 age-matched healthy controls.
A Simple Proof That the Curl Defined as Circulation Density Is a Vector-Valued Function, and an Alternative Approach to Proving Stoke’s Theorem  [PDF]
David McKay
Advances in Pure Mathematics (APM) , 2012, DOI: 10.4236/apm.2012.21007
Abstract: This article offers a simple but rigorous proof that the curl defined as a limit of circulation density is a vector-valued function with the standard Cartesian expression.
To signal or not to signal? Chemical communication by urine-borne signals mirrors sexual conflict in crayfish
Fiona C Berry, Thomas Breithaupt
BMC Biology , 2010, DOI: 10.1186/1741-7007-8-25
Abstract: Staged female-male pairings during the reproductive season often resulted in male mating attempts. Blocking female urine release in such pairings prevented any male courtship behaviour. Artificial introduction of female urine re-established male mating attempts. Urine visualisation showed that female urine release coincides with aggressive behaviours but not with female submissive behaviour in reproductive interactions as well as in intersexual and intrasexual fights. In reproductive interactions, females predominately released urine during precopulatory aggression; males subsequently released significantly less urine during mating than in fights.Urine-blocking experiments demonstrate that female urine contains sex-specific components that elicit male mating behaviour. The coincidence of chemical signalling and aggressive behaviour in both females and males suggests that urine release has evolved as an aggressive signal in both sexes of crayfish. By limiting urine release to aggressive behaviours in reproductive interactions females challenge their potential mating partners at the same time as they trigger a sexual response. These double messages should favour stronger males that are able to overcome the resistance of the female. We conclude that the difference between the sexes in disclosing urine-borne information reflects their conflicting interests in reproduction. Males discontinue aggressive urine signalling in order to increase their chances of mating. Females resume urine signalling in connection with aggressive behaviour, potentially repelling low quality or sexually inactive males while favouring reproduction with high quality males.Sexual selection theory predicts that females will minimise risk and energy expenditure during courtship, due to their higher investment in offspring compared to males [1]. Asymmetry in the evolutionary interests of males and females can result in sexual conflicts over whether or not mating takes place [2]. Males try to maximis
Morphological Classification of Galaxies by Shapelet Decomposition in the Sloan Digital Sky Survey
Brandon C. Kelly,Timothy A. McKay
Physics , 2003, DOI: 10.1086/380934
Abstract: We describe application of the `shapelet' linear decomposition of galaxy images to morphological classification using images of $\sim$ 3000 galaxies from the Sloan Digital Sky Survey. After decomposing the galaxies we perform a principal component analysis to reduce the number of dimensions of the shapelet space to nine. We find that each of these nine principal components contains unique morphological information, and give a description of each principal component's contribution to a galaxy's morphology. We find that galaxies of differing Hubble type separate cleanly in the shapelet space. We apply a Gaussian mixture model to the 9-dimensional space spanned by the principal components and use the results as a basis for classification. Using the mixture model, we separate galaxies into seven classes and give a description of each class's physical and morphological properties. We find that several of the mixture model classes correlate well with the traditional Hubble types both in their morphology and their physical parameters (e.g., color, velocity dispersions, etc.). In addition, we find an additional class of late-type morphology but with high velocity dispersions and very blue color; most of these galaxies exhibit post-starburst activity. This method provides an objective and quantitative alternative to traditional and subjective visual classification.
Asymptotic enumeration of symmetric integer matrices with uniform row sums
Brendan D. McKay,Jeanette C. McLeod
Mathematics , 2011,
Abstract: We investigate the number of symmetric matrices of non-negative integers with zero diagonal such that each row sum is the same. Equivalently, these are zero diagonal symmetric contingency tables with uniform margins, or loop-free regular multigraphs. We determine the asymptotic value of this number as the size of the matrix tends to infinity, provided the row sum is large enough. We conjecture that our answer is valid for all row sums.
A process evaluation of a "physical activity pathway" in the primary care setting
Fiona C Bull, Karen E Milton
BMC Public Health , 2010, DOI: 10.1186/1471-2458-10-463
Abstract: The LGM intervention was implemented in six general practices in London. Practices recruited patients either 'opportunistically' in routine consultations or by letter of invitation sent to patients on the hypertension disease register. A key component of the intervention was the delivery of a brief counselling session aimed at facilitating physical activity behaviour change. Data collection methods included electronic patient records, a practice survey and focus groups and interviews with practitioners.A total of 526 patients were considered for LGM, 378 via the 'opportunistic' recruitment method and 148 using the disease register approach. Patient interest in the brief counselling session was high although the actual delivery style and content varied between practitioners. Patients were directed towards a variety of physical activity opportunities including local leisure services and walking schemes.The learning from this pilot should inform a revised update of the LGM protocols before the planned dissemination of the intervention which is outlined in the Governments 'Be Active, Be Healthy' physical activity strategy. A robust assessment of effectiveness involving an experimental design and behaviour change measures is also warranted prior to wider dissemination.Participation in regular physical activity is associated with the prevention of chronic disease and the promotion of health and well-being[1]. Despite these benefits, national data show that in England 60% of men and approximately 70% of women are insufficiently active to benefit their health[2]. The estimated annual cost of physical inactivity in England is between £1 billion and £1.8 billion, with an average annual cost of £5 million for each Primary Care Trust[3].Promoting physical activity in primary care is recognised as an important and potentially effective approach[4-6]. In recent years a number of initiatives have been tested in the primary care setting including advice and counselling [7-9], the p
Characterization of two Pro-opiomelanocortin gene variants and their effects on carcass traits in beef cattle
Heather M Deobald, Fiona C Buchanan
BMC Genetics , 2011, DOI: 10.1186/1471-2156-12-2
Abstract: While developing a commercial real time PCR test for POMC c.288C>T a 12 bp deletion (POMC c.293_304delTTGGGGGCGCGG) was identified. The deletion results in the removal of four amino acids (a valine, two glycines, and an alanine). Both the POMC c.288C>T and the deletion were genotyped in 386 crossbred steers and evaluated for associations with carcass traits. The animals with one copy of the deletion had a significantly smaller carcass rib-eye area (7.91 cm2; P = 0.02) in comparison to homozygous normal animals. Significant associations were observed between POMC c.288C>T with start-of-finishing weight (SOF WT; P = 0.04), hot carcass weight (HCW; P = 0.02), average fat and grade fat (both P = 0.05), carcass rib-eye area (REA; P = 0.03) and marbling (P = 0.02).These results suggest that it could be beneficial for beef producers to know both the deletion and POMC c.288C>T genotypes when making marketing and culling decisions.The hypothalamus is a key area of the brain for appetite regulation. More specifically, there are two neuronal circuits, in the arcuate nucleus of the hypothalamus, that are important in both nutritional status and regulating energy homeostasis. One neuronal circuit contains the anorexigenic neuropeptides, including pro-opiomelanocortin (POMC), and the other circuit contains orexigenic peptides such as neuropeptide Y [1].Pro-opiomelanocortin is a prohormone that codes for many different peptides including adrenocorticotrophin (ACTH), alpha melanocyte stimulating hormone (α-MSH), beta melanocyte stimulating hormone (β-MSH), gamma melanocyte stimulating hormone (γ-MSH), and β-endorphin (β-END) some of which are involved in the appetite pathway [2]. The main POMC encoded anorectic peptide responsible for reductions in food intake and appetite is αMSH which reduces appetite when bound to melanocortin 4-receptor (MC4R) or melanocortin 3-receptor (MC3R); γ and β MSH also reduce appetite but not to the same magnitude as α-MSH.The prohormone POMC undergoes
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