Inhibition of G Protein-Activated Inwardly Rectifying K+ Channels by Phencyclidine

Addictive drugs, such as opioids, ethanol, cocaine, amphetamine, and phencyclidine (PCP), affect many functions of the nervous system and peripheral organs, resulting in severe health problems. G protein-activated inwardly rectifying K+ (GIRK, Kir3) channels play an important role in regulating neuronal excitability through activation of various Gi/o protein-coupled receptors including opioid and CB1 cannabinoid receptors. Furthermore, the channels are directly activated by ethanol and inhibited by cocaine at toxic levels, but not affected by methylphenidate, methamphetamine, and 3,4-methylenedioxymethamphetamine (MDMA) at toxic levels. The primary pharmacological action of PCP is blockade of N-methyl-D-aspartate (NMDA) receptor channels that are associated with its psychotomimetic effects. PCP also interacts with several receptors and channels at relatively high concentrations. However, the molecular mechanisms underlying the various effects of PCP remain to be clarified. Here, we investigated the effects of PCP on GIRK channels using the Xenopus oocyte expression system. PCP weakly but significantly inhibited GIRK channels at micromolar concentrations, but not Kir1.1 and Kir2.1 channels. The PCP concentrations effective in inhibiting GIRK channels overlap clinically relevant brain concentrations in severe intoxication. The results suggest that partial inhibition of GIRK channels by PCP may contribute to some of the toxic effects after overdose

Low-Frequency Electroacupuncture Improves Insulin Sensitivity in Obese Diabetic Mice through Activation of SIRT1/PGC-1α in Skeletal Muscle

Electroacupuncture (EA) has been observed to reduce insulin resistance in obesity and diabetes. However, the biochemical mechanism underlying this effect remains unclear. This study investigated the effects of low-frequency EA on metabolic action in genetically obese and type 2 diabetic db/db mice. Nine-week-old db/m and db/db mice were randomly divided into four groups, namely, db/m, db/m + EA, db/db, and db/db + EA. db/m + EA and db/db + EA mice received 3-Hz electroacupuncture five times weekly for eight consecutive weeks. In db/db mice, EA tempered the increase in fasting blood glucose, food intake, and body mass and maintained insulin levels. In EA-treated db/db mice, improved insulin sensitivity was established through intraperitoneal insulin tolerance test. EA was likewise observed to decrease free fatty acid levels in db/db mice; it increased protein expression in skeletal muscle Sirtuin 1 (SIRT1) and induced gene expression of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), nuclear respiratory factor 1 (NRF1), and acyl-CoA oxidase (ACOX). These results indicated that EA offers a beneficial effect on insulin resistance in obese and diabetic db/db mice, at least partly, via stimulation of SIRT1/PGC-1α, thus resulting in improved insulin signal

Blood flow in microchannel with stenosis measured by a confocal micro PTV system

Blood in microcircualtion is not a homogenous fluid but the suspension of Red Blood Cells(RBC). So individual RBCs behavior is essential to get good comprehension about the blood flow in microcirculation. In this study we observe the RBCs behavior through the stenosis by using confocal-micro- PTV system. And we can observe the difference of the cell free layer thickness according to Hct

Search for a stochastic background of 100-MHz gravitational waves with laser interferometers

This letter reports the results of a search for a stochastic background of gravitational waves (GW) at 100 MHz by laser interferometry. We have developed a GW detector, which is a pair of 75-cm baseline synchronous recycling (resonant recycling) interferometers. Each interferometer has a strain sensitivity of ~ 10^{-16} Hz^{-1/2} at 100 MHz. By cross-correlating the outputs of the two interferometers within 1000 seconds, we found h_{100}^2 Omega_{gw} < 6 times 10^{25} to be an upper limit on the energy density spectrum of the GW background in a 2-kHz bandwidth around 100 MHz, where a flat spectrum is assumed.Comment: Accepted by Phys.Rev.Lett.; 10 pages, 4 figure

Steering the Climate System: Using Inertia to Lower the Cost of Policy

Conventional wisdom holds that the efficient way to limit warming to a chosen level is to price carbon emissions at a rate that increases exponentially. We show that this “Hotelling” tax on carbon emissions is actually inefficient. The least-cost policy path takes advantage of the climate system’s inertia by growing more slowly than exponentially. Carbon dioxide temporarily overshoots the steady-state level consistent with the temperature limit, and the efficient carbon tax follows an inverse-U-shaped path. Economic models that assume exponentially increasing carbon taxes are overestimating the minimum cost of limiting warming, overestimating the efficient near-term carbon tax, and overvaluing technologies that mature sooner

A New Milky Way Satellite Discovered In The Subaru/Hyper Suprime-Cam Survey

We report the discovery of a new ultra-faint dwarf satellite companion of the Milky Way based on the early survey data from the Hyper Suprime-Cam Subaru Strategic Program. This new satellite, Virgo I, which is located in the constellation of Virgo, has been identified as a statistically significant (5.5 sigma) spatial overdensity of star-like objects with a well-defined main sequence and red giant branch in their color-magnitude diagram. The significance of this overdensity increases to 10.8 sigma when the relevant isochrone filter is adopted for the search. Based on the distribution of the stars around the likely main sequence turn-off at r ~ 24 mag, the distance to Virgo I is estimated as 87 kpc, and its most likely absolute magnitude calculated from a Monte Carlo analysis is M_V = -0.8 +/- 0.9 mag. This stellar system has an extended spatial distribution with a half-light radius of 38 +12/-11 pc, which clearly distinguishes it from a globular cluster with comparable luminosity. Thus, Virgo I is one of the faintest dwarf satellites known and is located beyond the reach of the Sloan Digital Sky Survey. This demonstrates the power of this survey program to identify very faint dwarf satellites. This discovery of VirgoI is based only on about 100 square degrees of data, thus a large number of faint dwarf satellites are likely to exist in the outer halo of the Milky Way.Comment: typos are corrected, 6 pages, 4 figures, accepted for publication in Ap

Association between the rs1465040 single-nucleotide polymorphism close to the transient receptor potential subfamily C member 3 (TRPC3) gene and postoperative analgesic requirements

AbstractAn association between postoperative analgesic requirements in subjects who underwent orthognathic surgery and the rs1465040 single-nucleotide polymorphism close to the transient receptor potential subfamily C member 3 (TRPC3) gene was suggested by our previous genome-wide association study. To verify this association, we analyzed the association between the rs1465040 SNP and analgesic requirements, including opioid requirements, after open abdominal surgery. The association between the rs1465040 SNP and postoperative analgesic requirements was confirmed in the open abdominal surgery group (P = 0.036), suggesting that the TRPC3 SNP may contribute to predicting postoperative analgesic requirements

Optimal Location of Two Laser-interferometric Detectors for Gravitational Wave Backgrounds at 100 MHz

Recently, observational searches for gravitational wave background (GWB) have been developed and given constraints on the energy density of GWB in a broad range of frequencies. These constraints have already resulted in the rejection of some theoretical models of relatively large GWB spectra. However, at 100 MHz, there is no strict upper limit from direct observation, though an indirect limit exists due to He4 abundance due to big-bang nucleosynthesis. In our previous paper, we investigated the detector designs that can effectively respond to GW at high frequencies, where the wavelength of GW is comparable to the size of a detector, and found that the configuration, a so-called synchronous-recycling interferometer is best at these sensitivity. In this paper, we investigated the optimal location of two synchronous-recycling interferometers and derived their cross-correlation sensitivity to GWB. We found that the sensitivity is nearly optimized and hardly changed if two coaligned detectors are located within a range 0.2 m, and that the sensitivity achievable in an experiment is far below compared with the constraint previously obtained in experiments.Comment: 17 pages, 6 figure