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Search Results: 1 - 10 of 299996 matches for " Fiona J Thompson "
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A microarray analysis of gene expression in the free-living stages of the parasitic nematode Strongyloides ratti
Fiona J Thompson, Gary LA Barker, Louise Hughes, Clare P Wilkes, Jane Coghill, Mark E Viney
BMC Genomics , 2006, DOI: 10.1186/1471-2164-7-157
Abstract: We have constructed an S. ratti cDNA microarray and used it to interrogate changes in gene expression during the free-living phase of the S. ratti life-cycle. We have found very extensive differences in gene expression between first-stage larvae (L1) passed in faeces and infective L3s preparing to infect hosts. In L1 stages there was comparatively greater expression of genes involved in growth. We have also compared gene expression in L2 stages destined to develop directly into infective L3s with those destined to develop indirectly into free-living adults. This revealed relatively small differences in gene expression. We find little evidence for the conservation of transcription profiles between S. ratti and S. stercoralis or C. elegans.This is the first multi-gene study of gene expression in S. ratti. This has shown that robust data can be generated, with consistent measures of expression within computationally determined clusters and contigs. We find inconsistencies between EST representation data and microarray hybridization data in the identification of genes with stage-specific expression and highly expressed genes. Many of the genes whose expression is significantly different between L1 and iL3s stages are unknown beyond alignments to predicted genes. This highlights the forthcoming challenge in actually determining the role of these genes in the life of S. ratti.Parasitic nematodes have complex life-cycles that are affected and controlled by factors both within and outwith their hosts. In the genus Strongyloides, the life-cycle, unusually, includes both an obligate female-only parasitic generation and a facultative dioecious adult free-living generation. In recent years there has been an increasingly detailed understanding of the factors that affect the development of the free-living phase of this life-cycle, particularly for the parasites of rats, S. ratti [1].S. ratti parasitic females lie embedded in the mucosa of the small intestine of their host. These
Familial relative risks for breast cancer by pathological subtype: a population-based cohort study
Nasim Mavaddat, Paul D Pharoah, Fiona Blows, Kristy E Driver, Elena Provenzano, Deborah Thompson, Robert J MacInnis, Mitul Shah, The SEARCH Team, Douglas F Easton, Antonis C Antoniou
Breast Cancer Research , 2010, DOI: 10.1186/bcr2476
Abstract: We computed breast cancer FRR for subtypes of breast cancer by comparing breast cancer incidence in relatives of breast cancer cases from a population-based series with known estrogen receptor (ER), progesterone receptor (PR) or human epidermal growth factor receptor 2 (HER2) status with that expected from the general population. We estimated the contribution to the FRR of genetic variants associated with breast cancer susceptibility using subtype-specific genotypic relative risks and allele frequencies for each variant.At least one marker was measured for 4,590 breast cancer cases, who reported 9,014 affected and unaffected first-degree female relatives. There was no difference between the breast cancer FRR for relatives of patients with ER-negative (FRR = 1.78, 95% confidence intervals (CI): 1.44 to 2.11) and ER-positive disease (1.82, 95% CI: 1.67 to 1.98), P = 0.99. There was some suggestion that the breast cancer FRR for relatives of patients with ER-negative disease was higher than that for ER-positive disease for ages of the relative less than 50 years old (FRR = 2.96, 95% CI: 2.04 to 3.87; and 2.05, 95% CI: 1.70 to 2.40 respectively; P = 0.07), and that the breast cancer FRR for relatives of patients with ER-positive disease was higher than for ER-negative disease when the age of the relative was greater than 50 years (FRR = 1.76, 95% CI: 1.59 to 1.93; and 1.41, 95% CI: 1.08 to 1.74 respectively, P = 0.06). We estimated that mutations in BRCA1 and BRCA2 explain 32% of breast cancer FRR for relatives of patients with ER-negative and 9.4% of the breast cancer FRR for relatives of patients with ER-positive disease. Twelve recently identified common breast cancer susceptibility variants were estimated to explain 1.9% and 9.6% of the FRR to relatives of patients with ER-negative and ER-positive disease respectively.FRR for breast cancer was significantly increased for both ER-negative and ER-positive disease. Including receptor status in conjunction with genetic
MDM2 SNP309 is associated with high grade node positive breast tumours and is in linkage disequilibrium with a novel MDM2 intron 1 polymorphism
Fiona EM Paulin, Mary O'Neill, Gillian McGregor, Andrew Cassidy, Alison Ashfield, Clinton W Ali, Alastair J Munro, Lee Baker, Colin A Purdie, David P Lane, Alastair M Thompson
BMC Cancer , 2008, DOI: 10.1186/1471-2407-8-281
Abstract: Intron 1 of MDM2 was PCR amplified and directly sequenced from 299 breast cancer patients and 275 cancer free controls and compared with clinical and pathological parameters.SNP309 was observed, for the control and breast cancer cohorts respectively, at frequencies of: T/T = 44.7% and 39.5%; G/T = 42.2% and 47.2%; G/G = 13.1% and 13.4%, indicating that SNP309 is not a predisposing factor for breast cancer. The 309G/G genotype was associated with high grade tumours (OR = 1.64, 95%CI = 1.06–2.53, p = 0.025) and greater nodal involvement (OR = 2.51, 95%CI = 1.26–4.98, p = 0.009). SNP309 was not associated with an earlier age of cancer diagnosis. No association was observed between genotype and age of breast cancer diagnosis when patients were stratified by menopausal status and estrogen receptor status. Three additional low frequency SNPs were identified: 344T>A, 285G>C and 443G>T, the latter two novel. SNP285 was in complete linkage disequilibrium with SNP309 (D' = 1.0) with the minor alleles being in phase with each other. Moreover, the 285C/C, 309G/G double homozygous genotype was only observed in the breast cancer cohort.SNP309G/G is associated with poor prognostic breast cancer features in the Scottish population. Additionally, a novel SNP, SNP285, that is in linkage disequilibrium with SNP309, may also have a role in breast tumorigenesis.MDM2, encoded by the human homologue of Murine Double Minute oncogene, is the principal negative regulator of p53, a transcription factor which plays key roles in cell division and response to DNA damage [1,2]. p53 is frequently mutated in cancer resulting in defective functions, including apoptotic and cell cycle arrest programs [3]. MDM2 controls p53 levels and activity by a number of different mechanisms, including direct inhibition of the transcriptional activity of p53 [4]. In addition, MDM2 acts as an E3 ubiquitin ligase targeting p53 for nuclear export and proteosomal degradation [5]. Furthermore, as MDM2 is a transcriptio
Macrophage Migration and Its Regulation by CSF-1
Fiona J. Pixley
International Journal of Cell Biology , 2012, DOI: 10.1155/2012/501962
Abstract: Macrophages are terminally differentiated cells of the mononuclear phagocytic lineage and develop under the stimulus of their primary growth and differentiation factor, CSF-1. Although they differentiate into heterogeneous populations, depending upon their tissue of residence, motility is an important aspect of their function. To facilitate their migration through tissues, macrophages express a unique range of adhesion and cytoskeletal proteins. Notably, macrophages do not form large, stable adhesions or actin stress fibers but rely on small, short lived point contacts, focal complexes and podosomes for traction. Thus, macrophages are built to respond rapidly to migratory stimuli. As well as triggering growth and differentiation, CSF-1 is also a chemokine that regulates macrophage migration via activation the CSF-1 receptor tyrosine kinase. CSF-1R autophosphorylation of several intracellular tyrosine residues leads to association and activation of many downstream signaling molecules. However, phosphorylation of just one residue, Y721, mediates association of PI3K with the receptor to activate the major motility signaling pathways in macrophages. Dissection of these pathways will identify drug targets for the inhibition of diseases in which macrophages contribute to adverse outcomes. 1. Introduction Macrophages reside in almost every tissue of the body and, as a result of their adaptation to the different tissue microenvironments, adopt a diverse range of morphologies and carry out a variety of functions. Despite their heterogeneity, macrophages all originate from the pluripotent hematopoietic stem cell and, under the influence of hematopoietic growth factors, differentiate through several multipotent progenitor stages to lineage committed mononuclear phagocytic precursors in the bone marrow[1–3]. The mononuclear phagocyte system is comprised of the mononuclear phagocyte precursors, monoblasts, and promonocytes, as well as circulating monocytes and fully differentiated, tissue resident macrophages [1–4]. Colony-stimulating factor-1 (CSF-1) has long been recognized as the primary growth factor regulating the survival, proliferation, and differentiation of cells of the mononuclear phagocytic lineage [1, 3, 5]. It is also an essential differentiation factor for the bone resorbing osteoclast [6]. A spontaneously occurring inactivating mutation in the mouse CSF-1 gene (osteopetrotic, Csf-1op) is associated with reduced tissue macrophage numbers and a marked reduction in osteoclasts, and causes osteopetrosis along with other developmental defects [1, 7–9].
Assessing the usefulness of a novel MRI-based breast density estimation algorithm in a cohort of women at high genetic risk of breast cancer: the UK MARIBS study
Deborah J Thompson, Martin O Leach, Gek Kwan-Lim, Simon A Gayther, Susan J Ramus, Iqbal Warsi, Fiona Lennard, Michael Khazen, Emilie Bryant, Sadie Reed, Caroline RM Boggis, D Gareth Evans, Rosalind A Eeles, Douglas F Easton, Ruth ML Warren, The UK study of MRI screening for breast cancer in women at high risk (MARIBS)
Breast Cancer Research , 2009, DOI: 10.1186/bcr2447
Abstract: The analyses were based on MRI (n = 655) and mammography (n = 607) images obtained in the course of the UK multicentre magnetic resonance imaging breast screening (MARIBS) study of asymptomatic women aged 31 to 49 years who were at high genetic risk of breast cancer. The MRI percent and absolute dense volumes were estimated using our novel algorithm (MRIBview) while mammographic percent and absolute dense area were estimated using the Cumulus thresholding algorithm and also using a 21-point Visual Assessment scale for one medio-lateral oblique image per woman. We assessed the relationships of the MRI and mammographic measures to one another, to standard anthropometric and hormonal factors, to BRCA1/2 genetic status, and to breast cancer risk (60 cases) using linear and Poisson regression.MRI percent dense volume is well correlated with mammographic percent dense area (R = 0.76) but overall gives estimates 8.1 percentage points lower (P < 0.0001). Both show strong associations with established anthropometric and hormonal factors. Mammographic percent dense area, and to a lesser extent MRI percent dense volume were lower in BRCA1 carriers (P = 0.001, P = 0.010 respectively) but there was no association with BRCA2 carrier status. The study was underpowered to detect expected associations between percent density and breast cancer, but women with absolute MRI dense volume in the upper half of the distribution had double the risk of those in the lower half (P = 0.009).The MRIBview estimates of volumetric breast density are highly correlated with mammographic dense area but are not equivalent measures; the MRI absolute dense volume shows potential as a predictor of breast cancer risk that merits further investigation.Mammographic breast density is usually defined as the proportion of a mammographic image occupied by radiodense tissue (largely stromal and epithelial tissues, appearing as white regions) as opposed to nondense, fatty tissue (the darker regions of the image).
Mal/SRF Is Dispensable for Cell Proliferation in Drosophila
Barry J. Thompson
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0010077
Abstract: The Mal/SRF transcription factor is regulated by the level of G-actin in cells and has important roles in cell migration and other actin-dependent processes in Drosophila. A recent report suggests that Mal/SRF and an upstream regulator, Pico, are required for cell proliferation and tissue growth in Drosophila. I find otherwise. Mutation of Mal or SRF does not affect cell proliferation in the fly wing. Furthermore, I cannot reproduce the reported effects of Pico RNAi or Pico overexpression on body size. Nevertheless, I can confirm that overexpression of Pico or Mal causes tissue overgrowth specifically in the fly wing - where SRF is most highly expressed. My results indicate that Mal/SRF can promote tissue growth when abnormally active, but is not normally required for tissue growth during development.
Highlights of GeV gamma-ray astronomy
D. J. Thompson
Astrophysics and Space Sciences Transactions (ASTRA) , 2010, DOI: 10.5194/astra-6-59-2010
Abstract: Because high-energy gamma rays are primarily produced by high-energy particle interactions, the gamma-ray survey of the sky by the Fermi Gamma-ray Space Telescope offers a view of sites of cosmic ray production and interactions. Gamma-ray bursts, pulsars, pulsar wind nebulae, binary sources, and Active Galactic Nuclei are all phenomena that reveal particle acceleration through their gamma-ray emission. Diffuse Galactic gamma radiation, Solar System gamma-ray sources, and energetic radiation from supernova remnants are likely tracers of high-energy particle interactions with matter and photon fields. This paper will present a broad overview of the constantly changing sky seen with the Large Area Telescope (LAT) on the Fermi spacecraft.
Grand challenges in the physics of the sun and sun-like stars
Michael J. Thompson
Frontiers in Astronomy and Space Sciences , 2014, DOI: 10.3389/fspas.2014.00001
Helioseismology over the solar cycle
M. J. Thompson
Physics , 2010,
Abstract: Helioseismology has produced unprecedented measurements of the Sun's internal structure and dynamics over the past 25 years. Much of this work has been based on global helioseismology. Now local helioseismology too is showing its great promise. This review summarizes very briefly the principal global results that may be relevant to an understanding of the origins of solar magnetism. Recent results regarding the variation of frequencies over the solar cycle and the temporal variations of subsurface flows are briefly summarized.
Reaction mechanisms of pair transfer
Ian J. Thompson
Physics , 2012,
Abstract: The mechanisms of nuclear transfer reactions are described for the transfer of two nucleons from one nucleus to another. Two-nucleon overlap functions are defined in various coordinate systems, and their transformation coefficients given between coordinate systems. Post and prior couplings are defined for sequential transfer mechanisms, and it is demonstrated that the combination of `prior-post' couplings avoids non-orthogonality terms, but does not avoid couplings that do not have good zero-range approximations. The simultaneous and sequential mechanisms are demonstrated for the $^{124}$Sn(p,t)$^{122}$Sn reaction at 25 MeV using shell-model overlap functions. The interference between the various simultaneous and sequential amplitudes is shown.
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