Control of respiration by nitric oxide in Keilin-Hartree particles,mitochondria and SH-SY5Y neuroblastoma cells

The pattern of cytochrome c oxidase inhibition by nitric oxide (NO) was investigated polarographically using Keilin-Hartree particles, mitochondria and human neuroblastoma cells. NO reacts with purified cytochrome c oxidase forming either a nitrosyl- or a nitrite-inhibited derivative, displaying distinct kinetics and light sensitivity of respiration recovery in the absence of free NO. Keilin-Hartree particles or cells, respiring either on endogenous substrates alone or in the presence of ascorbate, as well as state 3and state 4mitochondria respiring on glutamate and malate, displayed the rapid recovery characteristic of the nitrite derivative. All systems, when respiring in the presence of tetramethyl-p-phenylenediamine, were characterised by the slower, light-sensitive recovery typical of the nitrosyl derivative. Together the results suggest that the reaction of NO with cytochrome c oxidase in situ follows two alternative inhibition pathways, depending on the electron flux through the respiratory chain.Received 1 April 2003; received after revision 22 May 2003; accepted 3 June 2003     

The dynamics of actin-based motility depend on surface parameters

In cells, actin polymerization at the plasma membrane is induced by the recruitment of proteins such as the Arp2/3 complex, and the zyxin/VASP complex. The physical mechanism of force generation by actin polymerization has been described theoretically using various approaches, but lacks support from experimental data. By the use of reconstituted motility medium, we find that the Wiskott Aldrich syndrome protein (WASP) subdomain, known as VCA, is sufficient to induce actin polymerization and movement when grafted on microspheres. Changes in the surface density of VCA protein or in the microsphere diameter markedly affect the velocity regime, shifting from a continuous to a jerky movement resembling that of the mutated 'hopping' Listeria. These results highlight how simple physical parameters such as surface geometry and protein density directly affect spatially controlled actin polymerization, and play a fundamental role in actin-dependent movement.     

Conditional predictability of daily exchange rates

At what forecast horizon is one time series more predictable than another? This paper applies the Diebold–Kilian conditional predictability measure to assess the out‐of‐sample performance of three alternative models of daily GBP/USD and DEM/USD exchange rate returns. Predictability is defined as a non‐linear statistic of a model's relative expected losses at short and long forecast horizons, allowing flexible choice of both the estimation procedure and loss function. The long horizon is set to 2 weeks and one month ahead and forecasts evaluated according to MSE loss. Bootstrap methodology is used to estimate the data's conditional predictability using GARCH models. This is then compared to predictability under a random walk and a model using the prediction bias in uncovered interest parity (UIP). We find that both exchange rates are less predictable using GARCH than using a random walk, but they are more predictable using UIP than a random walk. Predictability using GARCH is relatively higher for the 2‐weeks‐than for the 1‐month long forecast horizon. Comparing the results using a random walk to that using UIP reveals ‘pockets’ of predictability, that is, particular short horizons for which predictability using the random walk exceeds that using UIP, or vice versa. Overall, GBP/USD returns appear more predictable than DEM/USD returns at short horizons. Copyright © 2002 John Wiley & Sons, Ltd.     

TRPA1 is a candidate for the mechanosensitive transduction channel of vertebrate hair cells

Mechanical deflection of the sensory hair bundles of receptor cells in the inner ear causes ion channels located at the tips of the bundle to open, thereby initiating the perception of sound. Although some protein constituents of the transduction apparatus are known, the mechanically gated transduction channels have not been identified in higher vertebrates. Here, we investigate TRP (transient receptor potential) ion channels as candidates and find one, TRPA1 (also known as ANKTM1), that meets criteria for the transduction channel. The appearance of TRPA1 messenger RNA expression in hair cell epithelia coincides developmentally with the onset of mechanosensitivity. Antibodies to TRPA1 label hair bundles, especially at their tips, and tip labelling disappears when the transduction apparatus is chemically disrupted. Inhibition of TRPA1 protein expression in zebrafish and mouse inner ears inhibits receptor cell function, as assessed with electrical recording and with accumulation of a channel-permeant fluorescent dye. TRPA1 is probably a component of the transduction channel itself.