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Search Results: 1 - 10 of 155566 matches for " Ian H Sadler "
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Impaired gluconeogenesis in a porcine model of paracetamol induced acute liver failure
Konstantinos J Dabos, Henry R Whalen, Philip N Newsome, John A Parkinson, Neil C Henderson, Ian H Sadler, Peter C Hayes, John N Plevris
World Journal of Gastroenterology , 2011,
Abstract: AIM: To investigate glucose homeostasis and in particular gluconeogenesis in a large animal model of acute liver failure (ALF).METHODS: Six pigs with paracetamol induced ALF under general anaesthesia were studied over 25 h. Plasma samples were withdrawn every five hours from a central vein. Three animals were used as controls and were maintained under anaesthesia only. Using 1H NMR spectroscopy we identified most gluconeogenic amino acids along with lactate and pyruvate in the animal plasma samples.RESULTS: No significant changes were observed in the concentrations of the amino acids studied in the animals maintained under anaesthesia only. If we look at the ALF animals, we observed a statistically significant rise of lactate (P < 0.003) and pyruvate (P < 0.018) at the end of the experiments. We also observed statistically significant rises in the concentrations of alanine (P < 0.002), glycine (P < 0.005), threonine (P < 0.048), tyrosine (P < 0.000), phenylalanine (P < 0.000) and isoleucine (P < 0.01). Valine levels decreased significantly (P < 0.05).CONCLUSION: Our pig model of ALF is characterized by an altered gluconeogenetic capacity, an impaired tricarboxylic acid (TCA) cycle and a glycolytic state.
Age-Related Biomarkers Can be Modulated by Diet in the Rat  [PDF]
Hilary Anne MacQueen, Wassif Samuel Wassif, Ian Walker, Dawn Angela Sadler, Karen Evans
Food and Nutrition Sciences (FNS) , 2011, DOI: 10.4236/fns.2011.28120
Abstract: This study seeks to establish the normal serum concentrations of biochemical markers related to nutrition, inflammation and disease, and to investigate how the levels change with age and diet in the rat. To this end, we fed rats from weaning on three diets differing in their protein, carbohydrate and fatty acid content. The diets consisted of a control, nutritionally balanced diet, this same diet supplemented with 10% (wt/wt) beef tallow, and a diet that was high in fat and carbohydrate and low in protein. Blood samples from rats at two different ages, 3 months and 12 months, were then analysed. In control rats, with advancing age there was a general decrease in potassium, iron and serum albumin concentrations and in the activities of aspartate aminotransferase and alanine aminotransferase, and an increase in total and HDL cholesterol. These changes were modulated by diet: many of the age-related changes (serum concentrations of potassium, iron and cholesterol, and liver enzyme activities) were not observed in animals eating the high fat diet. In contrast, the high carbohydrate, high fat, low protein diet-fed animals showed several additional changes (serum concentrations of sodium, urea, creatinine and TG, and activity of alkaline phosphatase) that can be related to kidney, liver and cardiovascular health.
Niobium Uptake and Release by Bacterial Ferric Ion Binding Protein
Yanbo Shi,Ian Harvey,Dominic Campopiano,Peter J. Sadler
Bioinorganic Chemistry and Applications , 2010, DOI: 10.1155/2010/307578
Abstract: Ferric ion binding proteins (Fbps) transport across the periplasm and are vital for the virulence of many Gram negative bacteria. Iron(III) is tightly bound in a hinged binding cleft with octahedral coordination geometry involving binding to protein side chains (including tyrosinate residues) together with a synergistic anion such as phosphate. Niobium compounds are of interest for their potential biological activity, which has been little explored. We have studied the binding of cyclopentadienyl and nitrilotriacetato complexes to the Fbp from Neisseria gonorrhoeae by UV-vis spectroscopy, chromatography, ICP-OES, mass spectrometry, and Nb K-edge X-ray absorption spectroscopy. These data suggest that binds strongly to Fbp and that a dinuclear centre can be readily accommodated in the interdomain binding cleft. The possibility of designing niobium-based antibiotics which block iron uptake by pathogenic bacteria is discussed. 1. Introduction Following the therapeutic success of cisplatin, a large number of complexes of other metals have been studied. Nonplatinum complexes are of particular interest since they may display a lack of cross-resistance with cisplatin, bringing significant benefits for chemotherapy. Metallocene dihalides and pseudohalides of general formula [Cp2MX2] (M = Ti, V, Nb, Mo; X = F, Cl, Br, I, CN, SCN; Figure 1(a)), have attracted significant interest since they have shown activity towards a wide variety of murine and human tumors [1–9]. Titanocene dichloride [Cp2TiCl2] was the first non-platinum metal complex to enter clinical trials but was eventually abandoned owing to its high reactivity in aqueous solution which gives rise to formulation difficulties [10, 11]. Figure 1: (a) Metallocene dihalides with antitumor activity. Key: (M) = maximum activity; M = sporadic activity; M = no activity. (b) binding sites in bacterial ferric ion-binding proteins ( Neisseria gonorrhoeae or Haemophilus influenzae). Vanadocene-, molybdenocene-, and niobocene dichlorides also exhibit good activities. Niobocene dichloride (Cp2NbCl2) is an extremely potent cancerostatic agent against the Ehrich ascites tumour in CFI mice [12, 13]. Oxidation to reduces the tumor inhibiting properties [14] but potentially could also reduce toxic effects. Hence there is interest in further investigation of the biological chemistry of niobium complexes [15]. Iron is the single most important micronutrient for bacterial survival; it plays important roles in both pathogen virulence and host antimicrobial resistance [16–18]. Numerous pathogenic bacteria such as Neisseria
Responses to River Inundation Pressures Control Prey Selection of Riparian Beetles
Matt J. O'Callaghan, David M. Hannah, Ian Boomer, Mike Williams, Jon P. Sadler
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0061866
Abstract: Background Riparian habitats are subjected to frequent inundation (flooding) and are characterised by food webs that exhibit variability in aquatic/terrestrial subsidies across the ecotone. The strength of this subsidy in active riparian floodplains is thought to underpin local biodiversity. Terrestrial invertebrates dominate the fauna, exhibiting traits that allow exploitation of variable aquatic subsidies while reducing inundation pressures, leading to inter-species micro-spatial positioning. The effect these strategies have on prey selection is not known. This study hypothesised that plasticity in prey choice from either aquatic or terrestrial sources is an important trait linked to inundation tolerance and avoidance. Method/Principal Findings We used hydrological, isotopic and habitat analyses to investigate the diet of riparian Coleoptera in relation to inundation risk and relative spatial positioning in the floodplain. The study examined patch scale and longitudinal changes in utilisation of the aquatic subsidy according to species traits. Prey sourced from terrestrial or emerging/stranded aquatic invertebrates varied in relation to traits for inundation avoidance or tolerance strategies. Traits that favoured rapid dispersal corresponded with highest proportions of aquatic prey, with behavioural traits further predicting uptake. Less able dispersers showed minimal use of aquatic subsidy and switched to a terrestrial diet under moderate inundation pressures. All trait groups showed a seasonal shift in diet towards terrestrial prey in the early spring. Prey selection became exaggerated towards aquatic prey in downstream samples. Conclusions/Significance Our results suggest that partitioning of resources and habitat creates overlapping niches that increase the processing of external subsidies in riparian habitats. By demonstrating functional complexity, this work advances understanding of floodplain ecosystem processes and highlights the importance of hydrological variability. With an increasing interest in reconnecting rivers to their floodplains, these invertebrates represent a key functional element in ensuring that such reconnections have demonstrable ecological value.
Editorial
Swindlehurst A. Lee,Fischer Robert F. H.,Sadler Brian M.
EURASIP Journal on Wireless Communications and Networking , 2004,
Abstract:
First Report of a Toxic Nodularia spumigena (Nostocales/ Cyanobacteria) Bloom in Sub-Tropical Australia. I. Phycological and Public Health Investigations
Glenn B. McGregor,Ian Stewart,Barbara C. Sendall,Ross Sadler,Karen Reardon,Steven Carter,Dan Wruck,Wasa Wickramasinghe
International Journal of Environmental Research and Public Health , 2012, DOI: 10.3390/ijerph9072396
Abstract: Cyanobacterial blooms represent one of the most conspicuous and widespread waterborne microbial hazards to human and ecosystem health. Investigation of a cyanobacterial bloom in a shallow brackish water recreational cable ski lake in south-eastern Queensland, Australia revealed the dominance of the toxigenic species Nodularia spumigena. The bloom spanned three months, during which time cell concentrations exceeded human guideline thresholds for recreational risk, and concentrations of the hepatotoxic cyanotoxin nodularin exceeded 200 μg L ?1. Cyanotoxin origin and identification was confirmed by amplification of the ndaF-specific PCR product and sequencing of the 16S rRNA gene. From the limited data available leading up to, and throughout the bloom, it was not possible to establish the set of causative factors responsible for its occurrence. However a combination of factors including salinity, hydraulic retention time and nutrient status associated with an extended period of drought are likely to have contributed. This was the first known occurrence of this species in bloom proportions from sub-tropical Australia and as such represents a hitherto uncharacterized risk to human and ecosystem health. It highlights the need for adaptive monitoring regimes to ensure a comprehensive understanding of the potentially toxic cyanobacteria likely to inhabit any given region. Such monitoring needs to recognize that cyanobacteria have a significant capacity for range expansion that has been facilitated by recent changes in global climate.
Catalysis: transition-state molecular recognition?
Ian H. Williams
Beilstein Journal of Organic Chemistry , 2010, DOI: 10.3762/bjoc.6.117
Abstract: The key to understanding the fundamental processes of catalysis is the transition state (TS): indeed, catalysis is a transition-state molecular recognition event. Practical objectives, such as the design of TS analogues as potential drugs, or the design of synthetic catalysts (including catalytic antibodies), require prior knowledge of the TS structure to be mimicked. Examples, both old and new, of computational modelling studies are discussed, which illustrate this fundamental concept. It is shown that reactant binding is intrinsically inhibitory, and that attempts to design catalysts that focus simply upon attractive interactions in a binding site may fail. Free-energy changes along the reaction coordinate for SN2 methyl transfer catalysed by the enzyme catechol-O-methyl transferase are described and compared with those for a model reaction in water, as computed by hybrid quantum-mechanical/molecular-mechanical molecular dynamics simulations. The case is discussed of molecular recognition in a xylanase enzyme that stabilises its sugar substrate in a (normally unfavourable) boat conformation and in which a single-atom mutation affects the free-energy of activation dramatically.
``Natural'' Vacua in Hyperbolic Friedmann-Robertson-Walker Spacetimes
Ian H. Redmount
Physics , 1999, DOI: 10.1103/PhysRevD.60.104004
Abstract: Recent evidence indicates that the Universe is open, i.e., spatially hyperbolic, longstanding theoretical preferences to the contrary notwithstanding. This makes it possible to select a vacuum state, Fock space, and particle definition for a quantized field, by requiring concordance with ordinary flat-spacetime theory at late times. The particle-number basis states thus identified span the physical state space of the field at all times. This construction is demonstrated here explicitly for a massive, minimally coupled, linear scalar field in an open, radiation-dominated Friedmann-Robertson-Walker spacetime.
Cartesian Coordinate, Oblique Boundary, Finite Differences and Interpolation
Ian H Hutchinson
Physics , 2011,
Abstract: A numerical scheme is described for accurately accommodating oblique, non-aligned, boundaries, on a three-dimensional cartesian grid. The scheme gives second-order accuracy in the solution for potential of Poisson's equation using compact difference stencils involving only nearest neighbors. Implementation for general "Robin" boundary conditions and for boundaries between media of different dielectric constant for arbitrary-shaped regions is described in detail. The scheme also provides for the interpolation of field (potential gradient) which, despite first-order peak errors immediately adjacent to the boundaries, has overall second order accuracy, and thus provides with good accuracy what is required in particle-in-cell codes: the force. Numerical tests on the implementation confirm the scalings and the accuracy.
Localized Particle States and Dynamics Gravitational Effects
Ian H. Redmount
Physics , 2005, DOI: 10.1103/PhysRevD.73.044032
Abstract: Scalar particles--i.e., scalar-field excitations--in de Sitter space exhibit behavior unlike either classical particles in expanding space or quantum particles in flat spacetime. Their energies oscillate forever, and their interactions are spread out in energy. Here it is shown that these features characterize not only normal-mode excitations spread out over all space, but localized particles or wave packets as well. Both one-particle and coherent states of a massive, minimally coupled scalar field in de Sitter space, associated with classical wave packets, are constructed explicitly. Their energy expectation values and corresponding Unruh-DeWitt detector response functions are calculated. Numerical evaluation of these quantities for a simple set of classical wave packets clearly displays these novel features. Hence, given the observed accelerating expansion of the Universe, it is possible that observation of an ultralow-mass scalar particle could yield direct confirmation of distinct predictions of quantum field theory in curved spacetime.
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