Anandamide and arachidonic acid use epoxyeicosatrienoic acids to activate TRPV4 channels

TRPV4 is a widely expressed cation channel of the 'transient receptor potential' (TRP) family that is related to the vanilloid receptor VR1 (TRPV1). It functions as a Ca2+ entry channel and displays remarkable gating promiscuity by responding to both physical stimuli (cell swelling, innoxious heat) and the synthetic ligand 4alphaPDD. An endogenous ligand for this channel has not yet been identified. Here we show that the endocannabinoid anandamide and its metabolite arachidonic acid activate TRPV4 in an indirect way involving the cytochrome P450 epoxygenase-dependent formation of epoxyeicosatrienoic acids. Application of 5',6'-epoxyeicosatrienoic acid at submicromolar concentrations activates TRPV4 in a membrane-delimited manner and causes Ca2+ influx through TRPV4-like channels in vascular endothelial cells. Activation of TRPV4 in vascular endothelial cells might therefore contribute to the relaxant effects of endocannabinoids and their P450 epoxygenase-dependent metabolites on vascular tone.     

Identifying distinct classes of bladder carcinoma using microarrays

Bladder cancer is a common malignant disease characterized by frequent recurrences. The stage of disease at diagnosis and the presence of surrounding carcinoma in situ are important in determining the disease course of an affected individual. Despite considerable effort, no accepted immunohistological or molecular markers have been identified to define clinically relevant subsets of bladder cancer. Here we report the identification of clinically relevant subclasses of bladder carcinoma using expression microarray analysis of 40 well characterized bladder tumors. Hierarchical cluster analysis identified three major stages, Ta, T1 and T2-4, with the Ta tumors further classified into subgroups. We built a 32-gene molecular classifier using a cross-validation approach that was able to classify benign and muscle-invasive tumors with close correlation to pathological staging in an independent test set of 68 tumors. The classifier provided new predictive information on disease progression in Ta tumors compared with conventional staging (P < 0.005). To delineate non-recurring Ta tumors from frequently recurring Ta tumors, we analyzed expression patterns in 31 tumors by applying a supervised learning classification methodology, which classified 75% of the samples correctly (P < 0.006). Furthermore, gene expression profiles characterizing each stage and subtype identified their biological properties, producing new potential targets for therapy.     

A larval Devonian lungfish

Perhaps the most enduring of puzzles in palaeontology has been the identity of Palaeospondylus gunni Traquair, a tiny (5-60-mm) vertebrate fossil from the Middle Devonian period (approximately 385 Myr ago) of Scotland, first discovered in 1890 (refs 1-3). It is known principally from a single site (Achanarras Quarry, Caithness) where, paradoxically, it is extremely abundant, preserved in varved lacustrine deposits along with 13 other genera of fishes. Here we show that Palaeospondylus is the larval stage of a lungfish, most probably Dipterus valenciennesi Sedgwick and Murchison 1828 (ref. 5), and that development of the adult form requires a distinct metamorphosis. Palaeospondylus is the oldest known true larva of a vertebrate.     

The voltage dependence of NADPH oxidase reveals why phagocytes need proton channels

The enzyme NADPH oxidase in phagocytes is important in the body's defence against microbes: it produces superoxide anions (O2-, precursors to bactericidal reactive oxygen species). Electrons move from intracellular NADPH, across a chain comprising FAD (flavin adenine dinucleotide) and two haems, to reduce extracellular O2 to O2-. NADPH oxidase is electrogenic, generating electron current (I(e)) that is measurable under voltage-clamp conditions. Here we report the complete current-voltage relationship of NADPH oxidase, the first such measurement of a plasma membrane electron transporter. We find that I(e) is voltage-independent from -100 mV to >0 mV, but is steeply inhibited by further depolarization, and is abolished at about +190 mV. It was proposed that H+ efflux mediated by voltage-gated proton channels compensates I(e), because Zn2+ and Cd2+ inhibit both H+ currents and O2- production. Here we show that COS-7 cells transfected with four NADPH oxidase components, but lacking H+ channels, produce O2- in the presence of Zn2+ concentrations that inhibit O2- production in neutrophils and eosinophils. Zn2+ does not inhibit NADPH oxidase directly, but through effects on H+ channels. H+ channels optimize NADPH oxidase function by preventing membrane depolarization to inhibitory voltages.     

Forecasting the price of crude oil via convenience yield predictions

The paper develops an oil price forecasting technique which is based on the present value model of rational commodity pricing. The approach suggests shifting the forecasting problem to the marginal convenience yield, which can be derived from the cost‐of‐carry relationship. In a recursive out‐of‐sample analysis, forecast accuracy at horizons within one year is checked by the root mean squared error as well as the mean error and the frequency of a correct direction‐of‐change prediction. For all criteria employed, the proposed forecasting tool outperforms the approach of using futures prices as direct predictors of future spot prices. Vis‐à‐vis the random‐walk model, it does not significantly improve forecast accuracy but provides valuable statements on the direction of change. Copyright © 2007 John Wiley & Sons, Ltd.     

How a membrane agent buys goods in a membrane store

In this paper we consider a specific model of membrane systems, i. e. membrane systems with attributes. In these systems, the information is placed at the membranes in form of attributes, no objects are considered inside the membranes except for other membranes. The membrane system with attributes evolves according to rules that compute new values for the attributes from the attributes assigned to the membranes involved in the rule. The model of membrane systems with attributes allows us to specify business transactions in a precise way and to simulate different models for such transactions with a suitable tool for membrane systems with attributes.     

Dam-forming cacti and nitrogen enrichment in a pi?on-juniper woodland in northwestern Arizona

In a pi?on-juniper woodland in northwestern Arizona, connected basal cladodes of a prickly pear cactus ( Opuntia littoralis var. martiniana ) form check dams that cause deposition of N-rich detritus interspaces otherwise lacking litter. Seventy-eight percent of connected basal cladodes measured in transects grew at an angle (with respect to the slope contour) ≤ 45° -an orientation facilitating deposition of flood-borne debris. Soil total N was significantly greater ( P P = 0.0001) compared to adjacent interspaces. Soil total N and organic C above cactus dams were equal to areas beneath canopies (tree and shrub combined). Net NO 3 - (0-5 cm depth) above cactus dams was significantly greater ( P = 0.0001) than below cactus dams, at interspaces, and beneath canopies. Net NH 4 + (0-5 cm soil depth) above cactus dams was significantly greater ( P s ￣x = 0.625, P = 0.0001).     

A small carnivore survey technique

Thirty-nine previously unpublished reports of the endangered black-footed ferret from Wyoming are listed with dates, locations, number of animals, sources, and comments.