Evidence for a Functional Interaction between Integrins and G Protein-activated Inward Rectifier K+ Channels

Heteromultimeric G protein-activated inward rectifier K+ (GIRK) channels, abundant in heart and brain, help to determine the cellular membrane potential as well as the frequency and duration of electrical impulses. The sequence arginine-glycine-aspartate (RGD), located extracellularly between the first membrane-spanning region and the pore, is conserved among all identified GIRK subunits but is not found in the extracellular domain of any other cloned K+ channels. Many integrins, which, like channels, are integral membrane proteins, recognize this RGD sequence on other proteins, usually in the extracellular matrix. We therefore asked whether GIRK activity might be regulated by direct interaction with integrin. Here, we present evidence that mutation of the RGD site to RGE, particularly on the GIRK4 subunit, decreases or abolishes GIRK current. Furthermore, wild-type channels can be co-immunoprecipitated with integrin. The total cellular amount of expressed mutant GIRK channel protein is the same as the wild-type protein; however, the amount of mutant channel protein that localizes to the plasma membrane is decreased relative to wild-type, most likely accounting for the diminished GIRK current detected. GIRK channels appear to bind directly to integrin and to require this interaction for proper GIRK channel membrane localization and function

A comparison of soil moisture characteristics predicted by the Arya-Paris model with laboratory-measured data

Soil moisture characteristics predicted by the Arya-Paris model were compared with the laboratory measured data for 181 New Jersey soil horizons. For a number of soil horizons, the predicted and the measured moisture characteristic curves are almost coincident; for a large number of other horizons, despite some disparity, their shapes are strikingly similar. Uncertainties in the model input and laboratory measurement of the moisture characteristic are indicated, and recommendations for additional experimentation and testing are made

On the formation of cyclones and anticyclones in a rotating fluid

It is commonly observed that the columnar vortices that dominate the large scales in homogeneous, rapidly rotating turbulence are predominantly cyclonic. This has prompted us to ask how this asymmetry arises. To provide a partial answer to this we look at the process of columnar vortex formation in a rotating fluid and, in particular, we examine how a localized region of swirl (an eddy) can convert itself into a columnar structure by inertial wave propagation. We show that, when the Rossby number (Ro) is small, the vortices evolve into columnar eddies through the radiation of linear inertial waves. When the Rossby number is large, on the other hand, no such column is formed. Rather, the eddy bursts radially outward under the action of the centrifugal force. There is no asymmetry between cyclonic and anticyclonic eddies for these two regimes. However, cyclones and anticyclones behave differently in the intermediate regime of Ro~1. Here we find that the transition from columnar vortex formation to radial bursting occurs at lower values of Ro for anticyclones, with the transition for anticyclones occurring at Ro~0.5, and that for cyclones at Ro~2. Thus, in a homogeneous turbulence experiment conducted at, say, Ro=1, we would expect to see more cyclones than anticyclones. The reason for this asymmetry at Ro~1 is explained

Scotland, Catalonia and the “right” to self-determination: a comment suggested by Kathryn Crameri’s “Do Catalans Have the Right to Decide?

No abstract available

Environmental Circadian Disruption Elevates the IL-6 Response to Lipopolysaccharide in Blood

The immune system is regulated by circadian clocks within the brain and immune cells. Environmental circadian disruption (ECD), consisting of a 6-h phase advance of the light:dark cycle once a week for 4 weeks, elevates the inflammatory response to lipopolysaccharide (LPS) both in vivo and in vitro. This indicates that circadian disruption adversely affects immune function; however, it remains unclear how the circadian system regulates this response under ECD conditions. Here, we develop an assay using ex vivo whole-blood LPS challenge to investigate the circadian regulation of immune responses in mice and to determine the effects of ECD on these rhythms. LPS-induced IL-6 release in whole blood was regulated in a circadian manner, peaking during subjective day under both entrained and free-running conditions. This LPS-induced IL-6 release rhythm was associated with daily variation in both white blood cell counts and immune cell responsiveness. ECD increased the overall level of LPS-induced IL-6 release by increasing immune cell responsiveness and not by affecting immune cell number or the circadian regulation of this rhythm. This indicates that ECD produces pathological immune responses by increasing the proinflammatory responses of immune cells. Also, this newly developed whole blood assay can provide a noninvasive longitudinal method to quantify potential health consequences of circadian disruption in humans

Richness and Abundance of Carabidae and Staphylinidae (Coleoptera), in Northeastern Dairy Pastures Under Intensive Grazing

Dairy cattle has become popular to dairy farmers in the Northeast looking for management schemes to cut production costs. Carabidae (ground beetles) and Staphylinidae (rove beetles) are indicators of habitat disturbances, such as drainage of wetlands, or grassland for grazing animals, and their monitoring could provide one measure of ecosystem sustainability if intensive management systems expand or intensify in the future. Our objective was assess the abundance and species richness of these two beetle families under intensive grazing throughout Pennsylvania, southern New York and Vermont. We collected 4365 ground beetles (83 species) and 4,027 rove beetles (79 species) by pitfall traps in three years in Pennsylvania. Nine ground beetle species, Amara aenea, Poecilus chalcites, Pterostichus melanarius, Bembidion quadrimaculatum oppositum, Amara familiaris, Poecilus lucublandus, Agonum muelleri, Bembidion obtusum and Bembidion mimus represented 80% of the Carabidae collected. Five other species were new to Pennsylvania. Four rove beetle species, Philonthus cognatus, Meronera venustula, Amischa analis, and Philonthus various = (carbonarius), comprised 74% of the total Staphylinidae collected. Yearly distributions of the dominant species did not change significantly in the three years with A. aenea and P. cognatus being most abundant every year. A parasitic rove beetle, Aleochara tristis, was recovered for the first time in Pennsylvania and Vermont since its release in the 1960\u27s to control face fly, Musca autumnalis. Similar results were found in New York and Vermont. We collected 1,984 ground beetles (68 species). Pterostichus melanarius was most abundant. Pterostichus vernalis was detected for the first time in the United States (Vermont). It was previously reported from Montreal, Canada. We collected 843 rove beetles (45 species). Philonthus cognatus was the most abundant rove beetle. In addition, Tachinus corticinus, previously known only from Canada, was discovered for the first time in the United States in Vermont. Pastures in Pennsylvania were diverse, containing 14 species of forage plants and 17 weed species. Botanical composition was similar in New York and Vermont. Sixteen species of grasses and legumes made up 90% of the plant composition and 36 species of weeds made up the remainder. This di­verse plant ecosystem may explain the richness of ground and rove beetles in northeastern U.S. pastures because the heterogeneity in the plant population provided additional resources which can support a rich assemblage of beetles. Monitoring richness and abundance of Carabidae and Staphylinidae over three years in Pennsylvania suggests intensive grazing systems are eco­logically sustainable

Low Molecular Weight mRNA Encodes a Protein That Controls Serotonin 5-HT_(1c) and Acetylcholine M_1 Receptor Sensitivity in Xenopus Oocytes

Serotonin 5-HT_(1c) and acetylcholine M_1 receptors activate phosphoinositidase, resulting in an increased formation of IP_3 and 1,2 diacylglycerol. In Xenopus oocytes injected with mRNA encoding either of these receptors, Ca^(2+) released from intracellular stores in response to IP3 then opens Ca^(2+)-gated Cl^-channels. In the present experiments, oocytes expressing a transcript from a cloned mouse serotonin 5-HT_(1c) receptor were exposed to identical 15-s pulses of agonist, administered 2 min apart; the second current response was two to three times that of the first. However, in those oocytes coinjected with the 5-HT_(1c) receptor transcript and a low molecular weight fraction (0.3-1.5 kb) of rat brain mRNA, the second current response was ~50% of the first. Thus, the low molecular weight RNA encodes a protein (or proteins) that causes desensitization. Experiments using fura-2 or a Ca^(2+)-free superfusate indicated that desensitization of the 5-HT_(1c) receptor response does not result from a sustained elevation of intracellular Ca^(2+) level or require the entry of extracellular Ca^(2+). Photolysis of caged IP_3 demonstrated that an increase in IP_3 and a subsequent rise in Ca^(2+) do not produce desensitization of either the IP_3 or 5-HT_(1c) peak current responses. Furthermore, in oocytes coinjected with the low molecular weight RNA and a transcript from the rat M_1 acetylcholine receptor, the M_1 current response was greatly attenuated. Our data suggest that the proteins involved in attenuation of the M_1 current response and desensitization of the 5-HT_(1c) current response may be the same

Protein kinase C modulates the activity of a cloned gamma-aminobutyric acid transporter expressed in Xenopus oocytes via regulated subcellular redistribution of the transporter

We report that activators and inhibitors of protein kinase C (PKC) and protein phosphatases regulate the activity of a cloned rat brain gamma- aminobutyric acid (GABA) transporter (GAT1) expressed in Xenopus oocytes. Four compounds known to activate PKC increased GABA uptake 2- 3.5-fold over basal control levels. Inhibition of PKC by bisindolylmaleimide reduced basal GABA uptake 80% and blocked the phorbol 12-myristate 13-acetate (PMA)-induced stimulation of transport. Okadaic acid, a protein phosphatase inhibitor, stimulated transport 2.5- fold; a 4-fold increase in GABA uptake occurred when oocytes were treated with cyclosporin A, a specific inhibitor of protein phosphatase 2B. Modulation resulted in changes to Vmax but not to Km and was influenced by the functional expression level of the transporter protein; as expression level increased, the ability to up-regulate transporter activity decreased. Down-regulation of transporter activity was independent of expression level. Modulation did not occur through phosphorylation of the three consensus PKC sites predicted by the primary protein sequence since their removal had no effect on the susceptibility of the transporter to modulation by PMA or bisindolylmaleimide. Subcellular fractionation of oocyte membranes demonstrated that under basal level conditions, the majority of GAT1 was targeted to a cytoplasmic compartment corresponding to the trans- Golgi or low density vesicles. Stimulation of PKC with PMA resulted in a translocation of transporters from this compartment to the plasma membrane. At higher expression levels of GAT1 protein, a larger portion of GAT1 was found on the plasma membrane during basal level conditions and treatment with bisindolylmaleimide resulted in removal of these transporters from the plasma membrane. At expression levels demonstrated to be resistant to modulation by PMA, PMA-treatment still resulted in translocation of transporters from the cytoplasm to the plasma membrane. Thus, the inability of PMA to increase uptake at high expression of the GAT1 protein is due to saturation at a step subsequent to translocation. These findings 1) demonstrate the presence of a novel regulated secretory pathway in oocytes and 2) suggest a modulatory mechanism for neurotransmitter transporters that could have significant effects upon synaptic function

Nonlinear Electron Oscillations in a Viscous and Resistive Plasma

New non-linear, spatially periodic, long wavelength electrostatic modes of an electron fluid oscillating against a motionless ion fluid (Langmuir waves) are given, with viscous and resistive effects included. The cold plasma approximation is adopted, which requires the wavelength to be sufficiently large. The pertinent requirement valid for large amplitude waves is determined. The general non-linear solution of the continuity and momentum transfer equations for the electron fluid along with Poisson's equation is obtained in simple parametric form. It is shown that in all typical hydrogen plasmas, the influence of plasma resistivity on the modes in question is negligible. Within the limitations of the solution found, the non-linear time evolution of any (periodic) initial electron number density profile n_e(x, t=0) can be determined (examples). For the modes in question, an idealized model of a strictly cold and collisionless plasma is shown to be applicable to any real plasma, provided that the wavelength lambda >> lambda_{min}(n_0,T_e), where n_0 = const and T_e are the equilibrium values of the electron number density and electron temperature. Within this idealized model, the minimum of the initial electron density n_e(x_{min}, t=0) must be larger than half its equilibrium value, n_0/2. Otherwise, the corresponding maximum n_e(x_{max},t=tau_p/2), obtained after half a period of the plasma oscillation blows up. Relaxation of this restriction on n_e(x, t=0) as one decreases lambda, due to the increase of the electron viscosity effects, is examined in detail. Strong plasma viscosity is shown to change considerably the density profile during the time evolution, e.g., by splitting the largest maximum in two.Comment: 16 one column pages, 11 figures, Abstract and Sec. I, extended, Sec. VIII modified, Phys. Rev. E in pres