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Search Results: 1 - 10 of 402019 matches for " Clare M. Reynolds "
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Pre-Weaning Growth Hormone Treatment Ameliorates Bone Marrow Macrophage Inflammation in Adult Male Rat Offspring following Maternal Undernutrition
Clare M. Reynolds, Minglan Li, Clint Gray, Mark H. Vickers
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0068262
Abstract: Maternal undernutrition (UN) is associated with the development of obesity and metabolic complications in adult offspring. While the role of inflammation in obesity and related comorbidities has been well established, there is little evidence regarding the effects of maternal UN-induced programming on immune function in male adult offspring. This study examines the effects growth hormone (GH), which is known to induce anti-inflammatory effects, on maternal UN-induced bone marrow macrophage (BMM) function in adult male offspring. Sprague-Dawley rats were assigned to chow (C) or UN (50% ad libitum; UN) diet throughout gestation. Male C and UN pups received saline (CS/UNS) or GH (2.5 μg/g/d; CGH/UNGH) from day 3–21. Bone marrow hematopoietic cells were differentiated to a macrophage phenotype in the presence of M-CSF (50 ng/ml). Differentiated bone marrow macrophages (BMM) were stimulated with LPS (100 ng/ml) for 6 h. UNS-derived BMM had significantly increased secretion and expression of IL-1β and IL-6 following LPS stimulation. This was accompanied by increased expression of IL-1R1, IL-6R and TLR4. Pre-weaning GH treatment reversed this pro-inflammatory phenotype. Furthermore UNGH displayed increased expression of markers of alternative (M2) macrophage activation, mannose receptor and PPARγ. This study demonstrates that fetal UN exposure primes hematopoietic immune cells to a more potent pro-inflammatory phenotype with heightened cytokine secretion and receptor expression. Furthermore these cells are pre-disposed to pro-inflammatory M1 macrophage phenotype which has wide-reaching and important effects in terms of obesity and metabolic disease.
Pre-Weaning Growth Hormone Treatment Reverses Hypertension and Endothelial Dysfunction in Adult Male Offspring of Mothers Undernourished during Pregnancy
Clint Gray, Minglan Li, Clare M. Reynolds, Mark H. Vickers
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0053505
Abstract: Maternal undernutrition results in elevated blood pressure (BP) and endothelial dysfunction in adult offspring. However, few studies have investigated interventions during early life to ameliorate the programming of hypertension and vascular disorders. We have utilised a model of maternal undernutrition to examine the effects of pre-weaning growth hormone (GH) treatment on BP and vascular function in adulthood. Female Sprague-Dawley rats were fed either a standard control diet (CON) or 50% of CON intake throughout pregnancy (UN). From neonatal day 3 until weaning (day 21), CON and UN pups received either saline (CON-S, UN-S) or GH (2.5 ug/g/day)(CON-GH, UN-GH). All dams were fed ad libitum throughout lactation. Male offspring were fed a standard diet until the end of the study. Systolic blood pressure (SBP) was measured at day 150 by tail cuff plethysmography. At day 160, intact mesenteric vessels mounted on a pressure myograph. Responses to pressure, agonist-induced constriction and endothelium-dependent vasodilators were investigated to determine vascular function. SBP was increased in UN-S groups and normalised in UN-GH groups (CON-S 121±2 mmHg, CON-GH 115±3, UN-S 146±3, UN-GH 127±2). Pressure mediated dilation was reduced in UN-S offspring and normalised in UN-GH groups. Vessels from UN-S offspring demonstrated a reduced constrictor response to phenylephrine and reduced vasodilator response to acetylcholine (ACh). Furthermore, UN-S offspring vessels displayed a reduced vasodilator response in the presence of L-NG-Nitroarginine Methyl Ester (L-NAME), carbenoxolone (CBX), L-NAME and CBX, Tram-34 and Apamin. UN-GH vessels showed little difference in responses when compared to CON and significantly increased vasodilator responses when compared to UN-S offspring. Pre-weaning GH treatment reverses the negative effects of maternal UN on SBP and vasomotor function in adult offspring. These data suggest that developmental cardiovascular programming is potentially reversible by early life GH treatment and that GH can reverse the vascular adaptations resulting from maternal undernutrition.
Effects of Taurine Supplementation on Hepatic Markers of Inflammation and Lipid Metabolism in Mothers and Offspring in the Setting of Maternal Obesity
Minglan Li, Clare M. Reynolds, Deborah M. Sloboda, Clint Gray, Mark H. Vickers
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0076961
Abstract: Maternal obesity is associated with obesity and metabolic disorders in offspring. However, intervention strategies to reverse or ameliorate the effects of maternal obesity on offspring health are limited. Following maternal undernutrition, taurine supplementation can improve outcomes in offspring, possibly via effects on glucose homeostasis and insulin secretion. The effects of taurine in mediating inflammatory processes as a protective mechanism has not been investigated. Further, the efficacy of taurine supplementation in the setting of maternal obesity is not known. Using a model of maternal obesity, we examined the effects of maternal taurine supplementation on outcomes related to inflammation and lipid metabolism in mothers and neonates. Time-mated Wistar rats were randomised to either: 1) control : control diet during pregnancy and lactation (CON); 2) CON supplemented with 1.5% taurine in drinking water (CT); 3) maternal obesogenic diet (high fat, high fructose) during pregnancy and lactation (MO); or 4) MO supplemented with taurine (MOT). Maternal and neonatal weights, plasma cytokines and hepatic gene expression were analysed. A MO diet resulted in maternal hyperinsulinemia and hyperleptinemia and increased plasma glucose, glutamate and TNF-α concentrations. Taurine normalised maternal plasma TNF-α and glutamate concentrations in MOT animals. Both MO and MOT mothers displayed evidence of fatty liver accompanied by alterations in key markers of hepatic lipid metabolism. MO neonates displayed a pro-inflammatory hepatic profile which was partially rescued in MOT offspring. Conversely, a pro-inflammatory phenotype was observed in MOT mothers suggesting a possible maternal trade-off to protect the neonate. Despite protective effects of taurine in MOT offspring, neonatal mortality was increased in CT neonates, indicating possible adverse effects of taurine in the setting of normal pregnancy. These data suggest that maternal taurine supplementation may ameliorate the adverse effects observed in offspring following a maternal obesogenic diet but these effects are dependent upon prior maternal nutritional background.
Timing of Maternal Exposure to a High Fat Diet and Development of Obesity and Hyperinsulinemia in Male Rat Offspring: Same Metabolic Phenotype, Different Developmental Pathways?
Graham J. Howie,Deborah M. Sloboda,Clare M. Reynolds,Mark H. Vickers
Journal of Nutrition and Metabolism , 2013, DOI: 10.1155/2013/517384
Abstract: Objective. Offspring born to mothers either fed an obesogenic diet throughout their life or restricted to pregnancy and lactation demonstrate obesity, hyperinsulinemia, and hyperleptinemia, irrespective of their postweaning diet. We examined whether timing of a maternal obesogenic diet results in differential regulation of pancreatic adipoinsular and inflammatory signaling pathways in offspring. Methods. Female Wistar rats were randomized into 3 groups: (1) control (CONT): fed a control diet preconceptionally and during pregnancy and lactation; (2) maternal high fat (MHF): fed an HF diet throughout their life and during pregnancy and lactation; (3) pregnancy and lactation HF (PLHF): fed a control diet throughout life until mating, then HF diet during pregnancy and lactation. Male offspring were fed the control diet postweaning. Plasma and pancreatic tissue were collected, and mRNA concentrations of key factors regulating adipoinsular axis signaling were determined. Results. MHF and PLHF offspring exhibited increased adiposity and were hyperinsulinemic and hyperleptinemic compared to CONT. Despite a similar anthropometric phenotype, MHF and PLHF offspring exhibited distinctly different expression for key pancreatic genes, dependent upon maternal preconceptional nutritional background. Conclusions. These data suggest that despite using differential signaling pathways, obesity in offspring may be an adaptive outcome of early life exposure to HF during critical developmental windows. 1. Introduction Early life events contribute substantially to the likelihood of an individual becoming obese, although underlying mechanisms are not well understood. Obesity in women of reproductive age (15 to 44 years) is increasing rapidly, and up to 50% of women in this age range in the USA are now either overweight or obese [1]. This has translated to an exponential increase in the prevalence of obesity during pregnancy with up to 20% of women entering pregnancy with a BMI which would define them as obese [2]. Obesity in pregnancy increases the risks for complications of pregnancy including miscarriage, hypertension, and gestational diabetes [3–5]. Furthermore, it is now well established that maternal obesity leads to an increased risk of obesity and metabolic and cardiovascular disorders in offspring [6–9]. In view of the rising prevalence of obesity in pregnancy and its association with adverse maternal and offspring outcomes, there is a great deal of interest in understanding the mechanistic pathways that link maternal obesity and excess maternal nutrition to increased
Bi-directional gene set enrichment and canonical correlation analysis identify key diet-sensitive pathways and biomarkers of metabolic syndrome
Melissa J Morine, Jolene McMonagle, Sinead Toomey, Clare M Reynolds, Aidan P Moloney, Isobel C Gormley, Peadar ó Gaora, Helen M Roche
BMC Bioinformatics , 2010, DOI: 10.1186/1471-2105-11-499
Abstract: Here, we apply an approach to gene set enrichment analysis that allows for detection of bi-directional enrichment within a gene set. Furthermore, we apply canonical correlation analysis and Fisher's exact test, using plasma marker data with known clinical relevance to aid identification of the most important gene and pathway changes in our transcriptomic dataset. After a 28-day dietary intervention with high-CLA beef, a range of plasma markers indicated a marked improvement in the metabolic health of genetically obese mice. Tissue transcriptomic profiles indicated that the effects were most dramatic in liver (1270 genes significantly changed; p < 0.05), followed by muscle (601 genes) and adipose (16 genes). Results from modified GSEA showed that the high-CLA beef diet affected diverse biological processes across the three tissues, and that the majority of pathway changes reached significance only with the bi-directional test. Combining the liver tissue microarray results with plasma marker data revealed 110 CLA-sensitive genes showing strong canonical correlation with one or more plasma markers of metabolic health, and 9 significantly overrepresented pathways among this set; each of these pathways was also significantly changed by the high-CLA diet. Closer inspection of two of these pathways - selenoamino acid metabolism and steroid biosynthesis - illustrated clear diet-sensitive changes in constituent genes, as well as strong correlations between gene expression and plasma markers of metabolic syndrome independent of the dietary effect.Bi-directional gene set enrichment analysis more accurately reflects dynamic regulatory behaviour in biochemical pathways, and as such highlighted biologically relevant changes that were not detected using a traditional approach. In such cases where transcriptomic response to treatment is exceptionally large, canonical correlation analysis in conjunction with Fisher's exact test highlights the subset of pathways showing strongest cor
The Complexity of Temporal Logic over the Reals
M. Reynolds
Computer Science , 1999,
Abstract: It is shown that the decision problem for the temporal logic with until and since connectives over real-numbers time is PSPACE-complete.
Alkaline phosphatase activity in the subtropical ocean: insights from nutrient, dust and trace metal addition experiments
Claire Mahaffey,Sarah Reynolds,Clare E. Davis,Maeve Lohan
Frontiers in Marine Science , 2014, DOI: 10.3389/fmars.2014.00073
Abstract: Phosphorus is an essential nutrient for all life on earth. In the ocean, the most bioavailable form of phosphorus is inorganic phosphate, but in the extensive subtropical gyres, phosphate concentrations can be chronically low and limit primary productivity and nitrogen fixation. In these regions, organisms produce hydrolytic enzymes, such as alkaline phosphatase (AP), that enable them to utilize the more replete dissolved organic phosphorus (DOP) pool to meet their cellular phosphorus demands. In this study, we synthesized data from 14 published studies and present our own findings from two research cruises (D326 and D361) in the eastern subtropical Atlantic to explore the relationship between AP activity (APA) and nutrients, Saharan dust and trace metals. We found that below a threshold phosphate concentration of ~ 30 nM, APA increased with an inverse hyperbolic relationship with phosphate concentration. Meanwhile, DOP concentrations decreased with enhanced APA, indicating utilization of the DOP pool. We found APA rates were significantly higher in the subtropical Atlantic compared to the subtropical Pacific Ocean, even over the same low phosphate concentration range (0 to 50 nM). While the phosphate concentration may have a first order control on the APA rates, we speculate that other factors influence this basin scale contrast. Using bioassay experiments, we show that the addition of Saharan dust and zinc significantly increased the rate of APA. To our knowledge, our results are the first direct field-based evidence that APA is limited by zinc in the subtropical ocean. Further work is required to explore the relationship between trace metals such as iron and zinc, which are co-factors of phosphohydrolytic enzymes, specifically PhoX and PhoA, respectively, and APA in the ocean.
The Duhem-Quine thesis and the dark matter problem
M. A. Reynolds
Physics , 2015,
Abstract: There are few opportunities in introductory physics for a genuine discussion of the philosophy of science, especially in cases where the physical principles are straightforward and the mathematics is simple. Terrestrial classical mechanics satisfies these requirements, but students new to physics usually carry too many incorrect or misleading preconceptions about the subject for it to be analyzed epistemologically. The problem of dark matter, and especially the physics of spiral galaxy velocity rotation curves, is a straightforward application of Newton's laws of motion and gravitation, and is just enough removed from everyday experience to be analyzed from a fresh perspective. It is proposed to teach students about important issues in the philosophy of physics, including Bacon's induction, Popper's falsifiability, and the Duhem-Quine thesis, all in light of the dark matter problem. These issues can be discussed in an advanced classical mechanics course, or, with limited simplification, at the end of a first course in introductory mechanics. The goal is for students to understand at a deeper level how the physics community has arrived at the current state of knowledge.
Low Carbohydrate Diets in Type 2 Diabetes—A Translational Study  [PDF]
Peter M. Clifton, Leah T. Coles, Clare E. Galbraith
Journal of Diabetes Mellitus (JDM) , 2016, DOI: 10.4236/jdm.2016.62016
Abstract: Although intensive interventions with low carbohydrate diets compared with higher carbohydrate diets can reduce HbA1c in people with type 2 diabetes, it is not clear if simple advice to make modest reductions in carbohydrate is effective in clinical practice. Forty-three people with type 2 diabetes and poor control (HbA1c > 7.5%) were randomized to receive 2 short education sessions over 6 months with a non-dietitian researcher on how to reduce carbohydrate intake by about 25% or to 2 control sessions in which the Australian Guide to Healthy Eating was provided. Hba1c and fasting glucose and lipids were measured at baseline and 3 months and 6 months. 33 volunteers attended a baseline visit; 27 completed 3 months and 24 6 months. HbA1c was reduced by 0.6% - 0.7% in the low carbohydrate diet group compared with the control group (P = 0.1). Fasting glucose was reduced by 2.3 mmol/L compared with the control group at 3 months (P < 0.03) only. Changes in HbA1c at 6 months were related to baseline HbA1c in the intervention group only. Although we have obtained suggestive evidence that a low carbohydrate diet can be successfully implemented in normal practice without professional help, our results are limited by low participant numbers and further studies are required.
The Potential of Targeting DNA Repair Deficiency in Acute Myeloid Leukemia  [PDF]
Clare M. Crean, Ken I. Mills, Kienan I. Savage
Journal of Cancer Therapy (JCT) , 2017, DOI: 10.4236/jct.2017.88060
Abstract: Acute myeloid leukemia (AML) is a clonal heterogeneous disease of the myeloid white blood cells. It is characterised by an accumulation of immature blast cells and a number of chromosomal and genetic mutations have been identified. In both de novo and therapy-related AML, defective DNA repair mechanisms are responsible for some of these genetic abnormalities. Targeting the DNA repair mechanism has been shown to be successful against certain forms of solid tumors and may represent a novel therapeutic approach for AML.
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