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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.
The Probability Distribution of the Elastic Properties of Pure Metals  [PDF]
Clint Steele
Applied Mathematics (AM) , 2014, DOI: 10.4236/am.2014.56085

While there are many published data on the average properties of elasticity for metals, there is little on the expected randomness. This is despite the known randomness of the elasticity of the grains that make up metals. It seems implicitly assumed that due to pseudo-isotropy, the average is all that is of concern. But how does one know if this is always the case? By creating a simple model of a metal, it is shown that for typical metal samples the randomness is negligible. However, as samples become smaller, it is possible to estimate the randomness based on information about the properties of grains within the metal. Further, due to the central limit theorem, which is implied by the model, a Gaussian distribution can be expected. This can be used in an evolutionary approach to generating a distribution for further probabilistic analysis of a respective system.

Adult-Onset Obesity Reveals Prenatal Programming of Glucose-Insulin Sensitivity in Male Sheep Nutrient Restricted during Late Gestation
Philip Rhodes,Jim Craigon,Clint Gray,Stuart M. Rhind,Paul T. Loughna,David S. Gardner
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0007393
Abstract: Obesity invokes a range of metabolic disturbances, but the transition from a poor to excessive nutritional environment may exacerbate adult metabolic dysfunction. The current study investigated global maternal nutrient restriction during early or late gestation on glucose tolerance and insulin sensitivity in the adult offspring when lean and obese.
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.
Deconstructing the Web –a curriculum for media students
Clint Cockcroft
South African Journal of Information Management , 2009, DOI: 10.4102/sajim.v2i2/3.96
Numerical integration of thermal noise in relativistic hydrodynamics
Clint Young
Physics , 2013, DOI: 10.1103/PhysRevC.89.024913
Abstract: Thermal fluctuations affect the dynamics of systems near critical points, the evolution of the early universe, and two-particle correlations in heavy-ion collisions. For the latter, numerical simulations of nearly-ideal, relativistic fluids are necessary. The correlation functions of noise in relativistic fluids are calculated, stochastic integration of the noise in 3+1-dimensional viscous hydrodynamics is implemented, and the effect of noise on observables in heavy-ion collisions is discussed. Thermal fluctuations will cause significant variance in the event-by-event distributions of integrated v2 while changing average values even when using the same initial conditions, suggesting that including thermal noise will lead to refitting of the hydrodynamical parameters with implications for understanding the physics of hot QCD.
How to show a set is not algebraic
Clint McCrory
Mathematics , 2001,
Abstract: We revisit Akbulut and King's first example of a compact semialgebraic set which satisfies Sullivan's local Euler characteristic condition, but which is not homeomorphic to an algebraic set. A nontrivial obstruction is computed using the link operator on the ring of constructible functions.
Excess Maternal Salt Intake Produces Sex-Specific Hypertension in Offspring: Putative Roles for Kidney and Gastrointestinal Sodium Handling
Clint Gray, Emad A. Al-Dujaili, Alexander J. Sparrow, Sheila M. Gardiner, Jim Craigon, Simon J.M. Welham, David S. Gardner
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0072682
Abstract: Hypertension is common and contributes, via cardiovascular disease, towards a large proportion of adult deaths in the Western World. High salt intake leads to high blood pressure, even when occurring prior to birth – a mechanism purported to reside in altered kidney development and later function. Using a combination of in vitro and in vivo approaches we tested whether increased maternal salt intake influences fetal kidney development to render the adult individual more susceptible to salt retention and hypertension. We found that salt-loaded pregnant rat dams were hypernatraemic at day 20 gestation (147±5 vs. 128±5 mmoles/L). Increased extracellular salt impeded murine kidney development in vitro, but had little effect in vivo. Kidneys of the adult offspring had few structural or functional abnormalities, but male and female offspring were hypernatraemic (166±4 vs. 149±2 mmoles/L), with a marked increase in plasma corticosterone (e.g. male offspring; 11.9 [9.3–14.8] vs. 2.8 [2.0–8.3] nmol/L median [IQR]). Furthermore, adult male, but not female, offspring had higher mean arterial blood pressure (effect size, +16 [9–21] mm Hg; mean [95% C.I.]. With no clear indication that the kidneys of salt-exposed offspring retained more sodium per se, we conducted a preliminary investigation of their gastrointestinal electrolyte handling and found increased expression of proximal colon solute carrier family 9 (sodium/hydrogen exchanger), member 3 (SLC9A3) together with altered faecal characteristics and electrolyte handling, relative to control offspring. On the basis of these data we suggest that excess salt exposure, via maternal diet, at a vulnerable period of brain and gut development in the rat neonate lays the foundation for sustained increases in blood pressure later in life. Hence, our evidence further supports the argument that excess dietary salt should be avoided per se, particularly in the range of foods consumed by physiologically immature young.
3D-Printed Microwell Arrays for Ciona Microinjection and Timelapse Imaging
Clint Gregory, Michael Veeman
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0082307
Abstract: Ascidians such as Ciona are close chordate relatives of the vertebrates with small, simple embryonic body plans and small, simple genomes. The tractable size of the embryo offers considerable advantages for in toto imaging and quantitative analysis of morphogenesis. For functional studies, Ciona eggs are considerably more challenging to microinject than the much larger eggs of other model organisms such as zebrafish and Xenopus. One of the key difficulties is in restraining the eggs so that the microinjection needle can be easily introduced and withdrawn. Here we develop and test a device to cast wells in agarose that are each sized to hold a single egg. This injection mold is fabricated by micro-resolution stereolithography with a grid of egg-sized posts that cast corresponding wells in agarose. This 3D printing technology allows the rapid and inexpensive testing of iteratively refined prototypes. In addition to their utility in microinjection, these grids of embryo-sized wells are also valuable for timelapse imaging of multiple embryos.
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