Agonists of protease-activated receptors 1 and 2 stimulate electrolyte secretion from mouse gallbladder

Cholecystitis is one of the most common gastrointestinal diseases. Inflammation induces the activation of proteases that can signal to cells by cleaving protease-activated receptors (PARs) to induce hemostasis, inflammation, pain, and repair. However, the distribution of PARs in the gallbladder is unknown, and their effects on gallbladder function have not been fully investigated. We localized immunoreactive PAR(1) and PAR(2) to the epithelium, muscle, and serosa of mouse gallbladder. mRNA transcripts corresponding to PAR(1) and PAR(2), but not PAR(4), were detected by RT-PCR and sequencing. Addition of thrombin and a PAR(1)-selective activating peptide (TFLLRN-NH(2)) to the serosal surface of mouse gallbladder mounted in an Ussing chamber stimulated an increase in short-circuit current in wild-type but not PAR(1) knockout mice. Similarly, serosally applied trypsin and PAR(2) activating peptide (SLIGRL-NH(2)) increased short-circuit current in wild-type but not PAR(2) knockout mice. Proteases and activating peptides strongly inhibited electrogenic responses to subsequent stimulation with the same agonist, indicating homologous desensitization. Removal of HCO(3)(-) ions from the serosal buffer reduced responses to thrombin and trypsin by >80%. Agonists of PAR(1) and PAR(2) increase intracellular Ca(2+) concentration in isolated and cultured gallbladder epithelial cells. The COX-2 inhibitor meloxicam and an inhibitor of CFTR prevented the stimulatory effect of PAR(1) but not PAR(2). Thus PAR(1) and PAR(2) are expressed in the epithelium of the mouse gallbladder, and serosally applied proteases cause a HCO(3)(-) secretion. The effects of PAR(1) but not PAR(2) depend on generation of prostaglandins and activation of CFTR. These mechanisms may markedly influence fluid and electrolyte secretion of the inflamed gallbladder when multiple proteases are generated.

An overview of Earth's global electric circuit and atmospheric conductivity

The Earth’s global atmospheric electric circuit depends on the upper and lower atmospheric boundaries formed by the ionosphere and the planetary surface. Thunderstorms and electrified rain clouds drive a DC current (∼1 kA) around the circuit, with the current carried by molecular cluster ions; lightning phenomena drive the AC global circuit. The Earth’s near-surface conductivity ranges from 10−7 S m−1 (for poorly conducting rocks) to 10−2 S m−1 (for clay or wet limestone), with a mean value of 3.2 S m−1 for the ocean. Air conductivity inside a thundercloud, and in fair weather regions, depends on location (especially geomagnetic latitude), aerosol pollution and height, and varies from ∼10−14 S m−1 just above the surface to 10−7 S m−1 in the ionosphere at ∼80 km altitude. Ionospheric conductivity is a tensor quantity due to the geomagnetic field, and is determined by parameters such as electron density and electron–neutral particle collision frequency. In the current source regions, point discharge (coronal) currents play an important role below electrified clouds; the solar wind-magnetosphere dynamo and the unipolar dynamo due to the terrestrial rotating dipole moment also apply atmospheric potential differences. Detailed measurements made near the Earth’s surface show that Ohm’s law relates the vertical electric field and current density to air conductivity. Stratospheric balloon measurements launched from Antarctica confirm that the downward current density is ∼1 pA m−2 under fair weather conditions. Fortuitously, a Solar Energetic Particle (SEP) event arrived at Earth during one such balloon flight, changing the observed atmospheric conductivity and electric fields markedly. Recent modelling considers lightning discharge effects on the ionosphere’s electric potential (∼+250 kV with respect to the Earth’s surface) and hence on the fair weather potential gradient (typically ∼130 V m−1 close to the Earth’s surface. We conclude that cloud-to-ground (CG) lightning discharges make only a small contribution to the ionospheric potential, and that sprites (namely, upward lightning above energetic thunderstorms) only affect the global circuit in a miniscule way. We also investigate the effects of mesoscale convective systems on the global circuit.

An overview of Earth’s global electric circuit and atmospheric conductivity

The Earth’s global atmospheric electric circuit depends on the upper and lower atmospheric boundaries formed by the ionosphere and the planetary surface. Thunderstorms and electrified rain clouds drive a DC current (∼1 kA) around the circuit, with the current carried by molecular cluster ions; lightning phenomena drive the AC global circuit. The Earth’s near-surface conductivity ranges from 10−7 S m−1 (for poorly conducting rocks) to 10−2 S m−1 (for clay or wet limestone), with a mean value of 3.2 S m−1 for the ocean. Air conductivity inside a thundercloud, and in fair weather regions, depends on location (especially geomagnetic latitude), aerosol pollution and height, and varies from ∼10−14 S m−1 just above the surface to 10−7 S m−1 in the ionosphere at ∼80 km altitude. Ionospheric conductivity is a tensor quantity due to the geomagnetic field, and is determined by parameters such as electron density and electron–neutral particle collision frequency. In the current source regions, point discharge (coronal) currents play an important role below electrified clouds; the solar wind-magnetosphere dynamo and the unipolar dynamo due to the terrestrial rotating dipole moment also apply atmospheric potential differences. Detailed measurements made near the Earth’s surface show that Ohm’s law relates the vertical electric field and current density to air conductivity. Stratospheric balloon measurements launched from Antarctica confirm that the downward current density is ∼1 pA m−2 under fair weather conditions. Fortuitously, a Solar Energetic Particle (SEP) event arrived at Earth during one such balloon flight, changing the observed atmospheric conductivity and electric fields markedly. Recent modelling considers lightning discharge effects on the ionosphere’s electric potential (∼+250 kV with respect to the Earth’s surface) and hence on the fair weather potential gradient (typically ∼130 V m−1 close to the Earth’s surface. We conclude that cloud-to-ground (CG) lightning discharges make only a small contribution to the ionospheric potential, and that sprites (namely, upward lightning above energetic thunderstorms) only affect the global circuit in a miniscule way. We also investigate the effects of mesoscale convective systems on the global circuit.

Comparison of methane produced by straw fed sheep in open-circuit respiration with methane predicted by fermentation characteristics measured by an in vitro gas procedure

Reducing carbon conversion of ruminally degraded feed into methane increases feed efficiency and reduces emission of this potent greenhouse gas into the environment. Accurate, yet simple, predictions of methane production of ruminants on any feeding regime are important in the nutrition of ruminants, and in modeling methane produced by them. The current work investigated feed intake, digestibility and methane production by open-circuit respiration measurements in sheep fed 15 untreated, sodium hydroxide (NaOH) treated and anhydrous ammonia (NH3) treated wheat, barley and oat straws. In vitro fermentation characteristics of straws were obtained from incubations using the Hohenheim gas production system that measured gas production, true substrate degradability, short-chain fatty acid production and efficiency of microbial production from the ratio of truly degraded substrate to gas volume. In the 15 straws, organic matter (OM) intake and in vivo OM digestibility ranged from 563 to 1201 g and from 0.464 to 0.643, respectively. Total daily methane production ranged from 13.0 to 34.4 l, whereas methane produced/kg OM matter apparently digested in vivo varied from 35.0 to 61.8 l. The OM intake was positively related to total methane production (R2 = 0.81, P<0.0001), and in vivo OM digestibility was also positively associated with methane production (R2 = 0.67, P<0.001), but negatively associated with methane production/kg digestible OM intake (R2 = 0.61, P<0.001). In the in vitro incubations of the 15 straws, the ratio of acetate to propionate ranged from 2.3 to 2.8 (P<0.05) and efficiencies of microbial production ranged from 0.21 to 0.37 (P<0.05) at half asymptotic gas production. Total daily methane production, calculated from in vitro fermentation characteristics (i.e., true degradability, SCFA ratio and efficiency of microbial production) and OM intake, compared well with methane measured in the open-circuit respiration chamber (y = 2.5 + 0.86x, R2 = 0.89, P<0.0001, Sy.x = 2.3). Methane production from forage fed ruminants can be predicted accurately by simple in vitro incubations combining true substrate degradability and gas volume measurements, if feed intake is known.

Short communication: plasma concentration of glucose-dependent insulinotropic polypeptide may regulate milk energy production in lactating dairy cows

In dairy cows, an increase in plasma concentration of glucose-dependent insulinotropic polypeptide (GIP) is associated with an increase in metabolizable energy intake, but the role of GIP in energy partitioning of dairy cattle is not certain. The objective of this study was to examine the relationship between plasma GIP concentrations and energy partitioning toward milk production. Four mid-lactation, primiparous, rumenfistulated Holstein-Friesian cows were fed a control diet of 55% forage and 45% concentrate [dry matter (DM) basis] in a 4 × 4 Latin square design with 4-wk periods. The 4 treatments were (1) control diet fed at 1000 and 1600 h, and (2) once-daily (1000 h) feeding, (3) twice daily (1000 and 1600 h) feeding, and (4) 4 times/d (1000, 1600, 2200 and 0400 h) feeding of the control diet plus 1 dose (1.75 kg on a DM basis at 0955 h) into the rumen of supplemental vegetable proteins (Amino Green; SCA NuTec Ltd., Thirsk, UK). Measurements of respiratory exchange and energy balance were obtained over 4 d during the last week of each period while cows were housed in open-circuit respiration chambers. Blood was collected from the jugular vein every 30 min for 12 h, using indwelling catheters, starting at 0800 h on d 20 of each period. Plasma GIP concentration was measured in samples pooled over each 5 consecutive blood samplings. The relationships between plasma GIP, DM intake, heat production, respiratory quotient, milk yield, and milk energy output were analyzed using linear correlation procedures, with metabolizable intake as a partial variant. Plasma GIP concentration was not correlated with heat production, or milk yield, but was positively correlated with milk energy yield (correlation coefficient = 0.67) and negatively correlated with RQ (correlation coefficient = −0.72). The correlations between GIP and RQ and milk energy output do not imply causality, but suggest that a role for GIP may exist in the regulation of energy metabolism in dairy cows.

Coherent EISCAT Svalbard Radar spectra from the dayside cusp/cleft and their implications for transient field-aligned currents

Naturally enhanced incoherent scatter spectra from the vicinity of the dayside cusp/cleft, interpreted as being due to plasma turbulence driven by short bursts of intense field-aligned current, are compared with high-resolution narrow-angle auroral images and meridian scanning photometer data. Enhanced spectra have been observed on many occasions in association with nightside aurora, but there has been only one report of such spectra seen in the cusp/cleft region. Narrow-angle images show considerable change in the aurora on timescales shorter than the 10-s radar integration period, which could explain spectra observed with both ion lines simultaneously enhanced. Enhanced radar spectra are generally seen inside or beside regions of 630-nm auroral emission, indicative of sharp F region conductivity gradients, but there appears also to be a correlation with dynamic, small-scale auroral forms of order 100 m and less in width.