Inhibition of electrogenic anion entry into rat liver mitochondria by N,N'-dicyclohexylcarbodiimide

AbstractThe carboxyl group reagent dicyclohexylcarbodiimide inhibits the electrogenic entry of Cl− and NO3− into rat liver mitochondria at alkaline pH. The inhibition is time dependent and 50% inhibition is obtained by the addition of 3–4 nmol DCCD/mg protein. The blockage of the pH-dependent anion-conducting pore appears to be unrelated to the other known actions of DCCD on rat liver mitochondria but seems similar to its effect on the uncoupling protein of brown adipose tissue

Oxo-stabilised phosphonium ylides as hydrogen bond acceptors

Oxo-stabilised phosphonium ylides are found to form crystalline hydrogen-bonded adducts with aromatic carboxylic acids as confirmed by X-ray diffraction. There is also strong hydrogen bonding in solution as indicated by 13C NMR spectroscopy and this confirmed adduct formation with acetic acid, benzamide, thiobenzamide, benzyl alcohol, benzenesulfinic acid and diphenylphosphinic acid. The X-ray structure of the benzamide adduct was also determined showing a hydrogen-bonded dimeric structure. A bis(stabilised ylide) was also prepared and is found to form a complex hydrogen-bonded adduct with benzoic acid, ethanol and water.Publisher PDFPeer reviewe

Quantifying extreme behaviour in geomagnetic activity

Understanding the extremes in geomagnetic activity is an important component in understanding just how severe conditions can become in the terrestrial space environment. Extreme activity also has consequences for technological systems. On the ground, extreme geomagnetic behavior has an impact on navigation and position accuracy and the operation of power grids and pipeline networks. We therefore use a number of decades of one-minute mean magnetic data from magnetic observatories in Europe, together with the technique of extreme value statistics, to provide a preliminary exploration of the extremes in magnetic field variations and their one-minute rates of change. These extremes are expressed in terms of the variations that might be observed every 100 and 200 years in the horizontal strength and in the declination of the field. We find that both measured and extrapolated extreme values generally increase with geomagnetic latitude (as might be expected), though there is a marked maximum in estimated extreme levels between about 53 and 62 degrees north. At typical midlatitude European observatories (55–60 degrees geomagnetic latitude), compass variations may reach approximately 3–8 degrees/minute, and horizontal field changes may reach 1000–4000 nT/minute, in one magnetic storm once every 100 years. For storm return periods of 200 years the equivalent figures are 4–11 degrees/minute and 1000–6000 nT/minute

Physiological concentrations of bile acids down-regulate agonist induced secretion in colonic epithelial cells

In patients with bile acid malabsorption, high concentrations of bile acids enter the colon and stimulate Cl− and fluid secretion, thereby causing diarrhoea. However, deoxycholic acid (DCA), the predominant colonic bile acid, is normally present at lower concentrations where its role in regulating transport is unclear. Thus, the current study set out to investigate the effects of physiologically relevant DCA concentrations on colonic epithelial secretory function. Cl− secretion was measured as changes in short-circuit current across voltage-clamped T84 cell monolayers. At high concentrations (0.5–1 mM), DCA acutely stimulated Cl− secretion but this effect was associated with cell injury, as evidenced by decreased transepithelial resistance (TER) and increased lactate dehydrogenase (LDH) release. In contrast, chronic (24 hrs) exposure to lower DCA concentrations (10–200 μM) inhibited responses to Ca2+ and cAMP-dependent secretagogues without altering TER, LDH release, or secretagogue-induced increases in intracellular second messengers. Other bile acids – taurodeoxycholic acid, chenodeoxycholic acid and cholic acid – had similar antisecretory effects. DCA (50 μM) rapidly stimulated phosphorylation of the epidermal growth factor receptor (EGFr) and both ERK and p38 MAPKs (mitogen-activated protein kinases). The EGFr inhibitor, AG1478, and the protein synthesis inhibitor, cycloheximide, reversed the antisecretory effects of DCA, while the MAPK inhibitors, PD98059 and SB203580, did not. In summary, our studies suggest that, in contrast to its acute prosecretory effects at pathophysiological concentrations, lower, physiologically relevant, levels of DCA chronically down-regulate colonic epithelial secretory function. On the basis of these data, we propose a novel role for bile acids as physiological regulators of colonic secretory capacity

Inequality in Care and Differences in Outcome Following Stroke in People With ESRD

Acknowledgments: MF is funded by a Kidney Research UK Training Fellowship and is supported by a grant from Darlinda’s Charity for Renal Research.Peer reviewedPublisher PD

The food superstore revolution: changing times, changing research agendas in the UK

This paper considers the changing scope of research into UK food superstores over a 30-year period. Rather than catalogue changing market shares by format, we seek instead to show how change links to national policy agendas. Academic research has evolved to address the growing complexities of the social, technological, economic and political impacts of the superstore format. We exemplify this by tracing the progression of retail change in Portsmouth, Hampshire, over 30 years. We discover that academic research can conflict with the preconceptions of some public policymakers. The position is exacerbated by a progressive decline in public information – and a commensurate rise in factual data held by commercial data companies – that leaves policymakers with a choice of which data to believe. This casts a shadow over the objectivity of macro-policy as currently formulated. Concerns currently arise because the UK Competition Commission (2008 but ongoing) starts each inquiry afresh with a search for recent data. Furthermore, it has recently called for changes to retail planning – the very arena in which UK superstore research commenced