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Search Results: 1 - 10 of 4289 matches for " Colin Duncan "
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Neuroinflammation induces glial aromatase expression in the uninjured songbird brain
Kelli A Duncan, Colin J Saldanha
Journal of Neuroinflammation , 2011, DOI: 10.1186/1742-2094-8-81
Abstract: Adult male zebra finches (Taeniopygia guttata) were given a penetrating injury to the entopallium. At several timepoints later, expression of aromatase, IL-1β-like, and IL-6-like were examined using immunohisotchemistry. A second set of zebra birds were exposed to phytohemagglutinin (PHA), an inflammatory agent, directly on the dorsal surface of the telencephalon without creating a penetrating injury. Expression of aromatase, IL-1β-like, and IL-6-like were examined using both quantitative real-time polymerase chain reaction to examine mRNA expression and immunohistochemistry to determine cellular expression. Statistical significance was determined using t-test or one-way analysis of variance followed by the Tukey Kramers post hoc test.Following injury in the zebra finch brain, cytokine expression occurs prior to aromatase expression. This temporal pattern suggests that cytokines may induce aromatase expression in the damaged zebra finch brain. Furthermore, evoking a neuroinflammatory response characterized by an increase in cytokine expression in the uninjured brain is sufficient to induce glial aromatase expression.These studies are among the first to examine a neuroinflammatory response in the songbird brain following mechanical brain injury and to describe a novel neuroimmune signal to initiate aromatase expression in glia.Damage to the homeotherm brain increases aromatase (estrogen synthase) in reactive astroglia [1-3]. Although constitutive aromatase is abundant and neuronal in the undamaged songbird brain, glial aromatase expression is rapidly upregulated following brain damage [1,4-8]. Increased transcription and translation of glial aromatase occurs following damage to the neuropil in songbirds and to a lesser extent in mammals [2,8-10]. In songbirds, this upregulation appears more rapid and robust, since the secondary wave of degeneration characteristic of the mammalian (including human) brain following TBI is only revealed in songbirds following inhibition
Modelling stellar coronae from surface magnetograms: the role of missing magnetic flux
Colin Johnstone,Moira Jardine,Duncan Mackay
Physics , 2010, DOI: 10.1111/j.1365-2966.2010.16298.x
Abstract: Recent advances in spectropolarimetry have allowed the reconstruction of stellar coronal magnetic fields. This uses Zeeman-Doppler magnetograms of the surface magnetic field as a lower boundary condition. The ZDI maps, however, suffer from the absence of information about the magnetic field over regions of the surface due to the presence of dark starspots and portions of the surface out of view due to a tilt in the rotation axis. They also suffer from finite resolution which leads to small scale field structures being neglected. This paper explores the effects of this loss of information on the extrapolated coronal fields. For this we use simulated stellar surface magnetic maps for two hypothetical stars. Using the potential field approximation, the coronal fields and emission measures are calculated. This is repeated for the cases of missing information due to, (i) starspots, (ii) a large area of the stellar surface out of view, (iii) a finite resolution. The largest effect on the magnetic field structure arises when a significant portion of the stellar surface remains out of view. This changes the nature of the field lines that connect to this obscured hemisphere. Nonetheless, the field structure in the visible hemisphere is reliably reproduced. Thus the calculation of the locations and surface filling factors of accretion funnels is reasonably well reproduced for the observed hemisphere. The decrease with height of the magnetic pressure, which is important in calculating disc truncation radii for accreting stars, is also largely unaffected in the equatorial plane. The fraction of surface flux that is open and therefore able to supply angular momentum loss in a wind, however, is often overestimated in the presence of missing flux.
The In Utero Programming Effect of Increased Maternal Androgens and a Direct Fetal Intervention on Liver and Metabolic Function in Adult Sheep
Kirsten Hogg, Charlotte Wood, Alan S. McNeilly, W. Colin Duncan
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0024877
Abstract: Epigenetic changes in response to external stimuli are fast emerging as common underlying causes for the pre-disposition to adult disease. Prenatal androgenization is one such model that results in reproductive and metabolic features that are present in conditions such as polycystic ovary syndrome (PCOS). We examined the effect of prenatal androgens on liver function and metabolism of adult sheep. As non-alcoholic fatty liver disease is increased in PCOS we hypothesized that this, and other important liver pathways including metabolic function, insulin–like growth factor (IGF) and steroid receptivity, would be affected. Pregnant ewes received vehicle control (C; n = 5) or testosterone propionate (TP; n = 9) twice weekly (100 mg; i.m) from d62–102 (gestation 147 days). In a novel treatment paradigm, a second cohort received a direct C (n = 4) or TP (20 mg; n = 7) fetal injection at d62 and d82. In adults, maternal TP exposure resulted in increased insulin secretion to glucose load (P<0.05) and the histological presence of fatty liver (P<0.05) independent of central obesity. Additionally, hepatic androgen receptor (AR; P<0.05), glucocorticoid receptor (GR; P<0.05), UDP- glucose ceramide glucosyltransferase (UGCG; P<0.05) and IGF1 (P<0.01) expression were upregulated. The direct fetal intervention (C and TP) led to early fatty liver changes in all animals without differential changes in insulin secretion. Furthermore, hepatic phosphoenolpyruvate carboxykinase (PEPCK) was up-regulated in the fetal controls (P<0.05) and this was opposed by fetal TP (P<0.05). Hepatic estrogen receptor (ERα; P<0.05) and mitogen activated protein kinase kinase 4 (MAP2K4; P<0.05) were increased following fetal TP exposure. Adult liver metabolism and signaling can be altered by early exposure to sex steroids implicating epigenetic regulation of metabolic disturbances that are common in PCOS.
Glucocorticoid Regulation of SLIT/ROBO Tumour Suppressor Genes in the Ovarian Surface Epithelium and Ovarian Cancer Cells
Rachel E. Dickinson, K. Scott Fegan, Xia Ren, Stephen G. Hillier, W. Colin Duncan
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0027792
Abstract: The three SLIT ligands and their four ROBO receptors have fundamental roles in mammalian development by promoting apoptosis and repulsing aberrant cell migration. SLITs and ROBOs have emerged as candidate tumour suppressor genes whose expression is inhibited in a variety of epithelial tumours. We demonstrated that their expression could be negatively regulated by cortisol in normal ovarian luteal cells. We hypothesised that after ovulation the locally produced cortisol would inhibit SLIT/ROBO expression in the ovarian surface epithelium (OSE) to facilitate its repair and that this regulatory pathway was still present, and could be manipulated, in ovarian epithelial cancer cells. Here we examined the expression and regulation of the SLIT/ROBO pathway in OSE, ovarian cancer epithelial cells and ovarian tumour cell lines. Basal SLIT2, SLIT3, ROBO1, ROBO2 and ROBO4 expression was lower in primary cultures of ovarian cancer epithelial cells when compared to normal OSE (P<0.05) and in poorly differentiated SKOV-3 cells compared to the more differentiated PEO-14 cells (P<0.05). Cortisol reduced the expression of certain SLITs and ROBOs in normal OSE and PEO-14 cells (P<0.05). Furthermore blocking SLIT/ROBO activity reduced apoptosis in both PEO-14 and SKOV-3 tumour cells (P<0.05). Interestingly SLIT/ROBO expression could be increased by reducing the expression of the glucocorticoid receptor using siRNA (P<0.05). Overall our findings indicate that in the post-ovulatory phase one role of cortisol may be to temporarily inhibit SLIT/ROBO expression to facilitate regeneration of the OSE. Therefore this pathway may be a target to develop strategies to manipulate the SLIT/ROBO system in ovarian cancer.
Using a decline in serum hCG between days 0–4 to predict ectopic pregnancy treatment success after single-dose methotrexate: a retrospective cohort study
Monika Skubisz, Philip Dutton, William Colin Duncan, Andrew W Horne, Stephen Tong
BMC Pregnancy and Childbirth , 2013, DOI: 10.1186/1471-2393-13-30
Abstract: We conducted a retrospective study of women (n=206) treated with single-dose methotrexate for ectopic pregnancy (pre-treatment serum hCG levels ≤3000 IU/L) at Scottish hospitals between 2006–2011. Women were divided into two cohorts based on whether their serum hCG levels rose or fell between days 0–4 after methotrexate. Treatment outcomes of women in each cohort were compared, and the test performance characteristics calculated. This methodology was repeated for the current measure (≥15% fall in serum hCG between days 4–7 of treatment) and an alternate early measure (<20% fall in serum hCG between days 0–4 of treatment), and all three measures were compared for their ability to predict medical treatment success.In our cohort, the positive predictive value of the current clinical measure was 89% (95% CI 84-94%) (121/136). A falling serum hCG between days 0–4 predicted treatment success in 85% (95% CI 79-92%) of cases (94/110) and a <20% fall in serum hCG between days 0–4 predicted treatment success in 94% (95% CI 88-100%) of cases (59/63). There was no significant difference in the ability of these tests to predict medical treatment success.We have verified that a decline in serum hCG between days 0–4 after methotrexate treatment for ectopic pregnancies, with pre-treatment serum hCG levels ≤3000 IU/L, provides an early indication of likelihood of treatment success, and performs just as well as the existing measure, which only provides prognostic information on day 7.Ectopic pregnancies occur in 1-2% of pregnancies [1]. Although potentially life threatening, the ability to non-invasively detect ectopic pregnancies before they rupture with ultrasound affords some women the option of medical management. Stovall et al.[2] first demonstrated the safety and efficacy of outpatient methotrexate to treat women with ectopic pregnancies in 1989, and today, approximately 25-30% of women presenting with this condition are eligible for such treatment [3,4].Quantification of serum
Agency at Work: A Dynamic Interpretive Approach  [PDF]
Colin Campbell
Sociology Mind (SM) , 2012, DOI: 10.4236/sm.2012.24047
Abstract: Roy’s 1950s paper “Banana Time” is used as the basis for an exploration of the nature and relationship of agency and action. Roy’s activity in playing his “game of work” is shown to be a feature of individual conduct that, despite possessing subjective meaning, is largely neglected by contemporary sociologists, mainly because of its covert character. What an examination of this aspect of his conduct suggests is the need to revise the conventional observational approach to the definition of the unit act by recognising that there may well be an additional actor’s covert definition sitting within the accepted social definition and that it is therefore necessary to use the criterion of attentionality to identify the unit act. An analysis of Roy’s game of work also helps to shed light on the possible relationship between action and agency, revealing that while the power of agency enables individuals to act, it is also frequently necessary for individuals to act in order to maintain or restore their power of agency. Finally, a consideration of the function fulfilled by Roy’s game of work shows that a behaviourist-style stimulus-response analysis of conduct is not at odds either with voluntarism or the adoption of the actor’s standpoint. This is because Roy demonstrates how actors are themselves lay behaviourists, fully aware of how they need to manipulate stimuli in order to produce desired responses in themselves.
Saving Lives: Timely Flash Flood Warnings in the UK  [PDF]
Colin Clark
Journal of Geoscience and Environment Protection (GEP) , 2017, DOI: 10.4236/gep.2017.52005
Flash floods are a major cause of death and destruction to property on a worldwide scale. In the UK sudden flooding has been the cause of the loss of over 60 lives during the last century. Forecasting these events to give enough warning is a major concern: after the 2004 flood at Boscastle, Cornwall UK the Environment Agency (2004) stated that it was not possible to provide a warning in such a fast reacting and small catchment. This is untrue since the Agency had already implemented a real time non-linear flow model as part of a flood warning system on the upper Brue in Somerset UK. This model is described in this paper as it has been applied to the Lynmouth flood of 1952, and briefly for the Boscastle catchment, both of which have an area of about 20 km2. The model uses locally measured SMD and saturated hydraulic conductivity data. With the addition of further parameters the model has been successfully used nationwide.
The Value of Using Unofficial Measurements of Rainfall: The Dublin Storm and Flood of June 1963  [PDF]
Colin Clark
Journal of Geoscience and Environment Protection (GEP) , 2019, DOI: 10.4236/gep.2019.72006
Abstract: Rainfall measurements are vital for the design of hydraulic structures, climate change studies, irrigation and land drainage works. The most important source of design rainfall data comes from convective storms. Accurate assessment of the storm rainfall requires a fairly dense network of raingauges. In 1963, such a storm took place over Dublin in Ireland. However, the existing raingauge network was insufficient to identify both the depth and pattern of rainfall. An appeal was made by Met Eireann for additional unofficial rainfall data. The result was remarkable in that the estimated maximum rainfall depth was found to be more than double the official value and that the resulting depth area analysis suggested a rainfall volume over a large area much bigger than the original isohyet map indicated. This result has huge implications for the estimation of maximum rainfall and dam safety assessment, especially in countries where the raingauge network has a low density. This paper first provides a description of the synoptic conditions that led to the storm, second an analysis of the rainfall data and how the unofficial measurements produced a very different depth area relationship; third, the social consequences of the resulting flood are described. Fourth, the storm is then placed in the context of other storms in the British Isles Finally the implications for rainfall measurement, gauge density and an example of how revised estimates of probable maximum precipitation (PMP) have been used to improve the safety and design standard of a flood detention dam are discussed.
Ectopic Pregnancy as a Model to Identify Endometrial Genes and Signaling Pathways Important in Decidualization and Regulated by Local Trophoblast
W. Colin Duncan, Julie L. V. Shaw, Stewart Burgess, Sarah E. McDonald, Hilary O. D. Critchley, Andrew W. Horne
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0023595
Abstract: The endometrium in early pregnancy undergoes decidualization and functional changes induced by local trophoblast, which are not fully understood. We hypothesized that endometrium from tubal ectopic pregnancy (EP) could be interrogated to identify novel genes and pathways involved in these processes. Gestation-matched endometrium was collected from women with EP (n = 11) and intrauterine pregnancies (IUP) (n = 13). RNA was extracted from the tissue. In addition, tissues were prepared for histological analysis for degree of decidualization. We compared a) the samples from EP that were decidualized (n = 6) with non-decidualized samples (n = 5), and b) the decidualized EP (n = 6) with decidualization-matched IUP (n = 6) samples using an Affymetrix gene array platform, with Ingenuity Pathway Analysis, combined with quantitative RT-PCR. Expression of PRL and IGFBP1 was used to confirm the degree of decidualization in each group. There were no differences in PRL or IGFBP1 expression in the decidualization-matched samples but a marked reduction (P<0.001) in the non-decidualized samples. Decidualization was associated with increased expression of 428 genes including SCARA5 (181-fold), DKK1 (71-fold) and PROK1 (32-fold), and decreased expression of 230 genes including MMP-7 (35-fold) and SFRP4 (21-fold). The top canonical pathways associated with these differentially expressed genes were Natural Killer Cell and Wnt/b-Catenin signaling. Local trophoblast was associated with much less alteration of endometrial gene expression with an increase in 56 genes, including CSH1 (8-fold), and a reduction in 29 genes including CRISP3 (8-fold). The top associated canonical pathway was Antigen Presentation. The study of endometrium from tubal EP may promote novel insights into genes involved in decidualization and those influenced by factors from neighboring trophoblast. This has afforded unique information not highlighted by previous studies and adds to our understanding of the endometrium in early pregnancy.
The clinical and functional relevance of microparticles induced by activated protein C treatment in sepsis
Margarita Pérez-Casal, Victoria Thompson, Colin Downey, Ingeborg Welters, Duncan Wyncoll, Jecko Thachil, Cheng Toh
Critical Care , 2011, DOI: 10.1186/cc10356
Abstract: This was an experimental study on clinical samples in an intensive care setting, and included patients with severe sepsis who fulfilled criteria for treatment with rhAPC. The number of CD13+ MPs from the patients were analysed to determine their origin. They were also quantified for endothelial protein C receptor (EPCR) and APC expression. Clinical relevance of these MPs were ascertained by comparing survival between the group receiving rhAPC (n = 25) and a control group of untreated patients (n = 25). MPs were also incubated with endothelial cells to analyse apoptotic gene expression, cytoprotection and anti-inflammatory effects.rhAPC treatment induced a significant increase in circulating MP-associated EPCR by flow cytometry (P < 0.05) and by quantitative ELISA (P < 0.005). APC expression also showed significant increases (P < 0.05). Numerically, CD13+ MPs were higher in rhAPC-treated survivors versus non-survivors. However, the number of non-survivors was low and this was not significantly different. APC on MPs was demonstrated to induce anti-apoptotic and endothelial barrier effects through the activation of endothelial PAR1.rhAPC treatment in patients with sepsis significantly increases circulating EPCR + MPs. These MPs were noted to express APC, which has specific anti-apoptotic and anti-inflammatory effects, with a non-significant correlative trend towards survival. This suggests that MPs could disseminate APC function and activate endothelial PAR1 at distal vascular sites.The presence of circulating microparticles (MPs) in septic patients is well recognised [1,2] and is inducible by thrombin [3], cytokines [4], lipopolysaccharide (LPS) [5] and collagen [6]. Derived from cell membrane shedding as a result of activation or apoptosis, circulating MPs constitute a marker of vascular and systemic disease [7]. Rearrangement of membrane phospholipids during MP release can result in increased phosphatidylserine availability with procoagulant activity. In patients wi
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