Control of synaptic transmission in the CNS through endocannabinoid-mediated retrograde signaling

Psychological and physiological effects of marijuana are caused by binding of its active component (Δ9-tetrahydrocannabinol) to cannabinoid receptors. The cannabinoid receptors belong to a family of G protein-coupled seven-transmembrane-domain receptors, and consist of type 1 (CBl) and type 2 (CB2) receptors with different distributions (Matsuda et al., 1990; Munro et al., 1993; Felder and Glass, 1998). The CBl receptor is expressed in the CNS, whereas the CB2 receptor is found in the immune system of the periphery (Klein et al., 1998). Activation of the CBl receptor induces various effects on neural functions (Di Marzo et al, 1998; Felder and Glass, 1998), including suppression of neurotransmitter release (Gifford and Ashby, 1996; Ishac et al., 1996; Shen et al., 1996; Katona et al, 1999; Hoffman and Lupica, 2000). Several molecules are identified as candidate endogenous ligands for cannabinoid receptors (endocannabinoids). Arachidonylethanolamide (anandamide) and 2-arachidonoylglycerol (2-AG), two major endocannabinoids, are reported to be synthesized from membrane phospholipids in an activity- and a Ca2+-dependent manner (Cadas et al, 1996; Stella et al, 1997; Di Marzo et al, 1998; Bisogno et al, 1999; PiomeUi et al, 2000). It is thought that they can diffuse out across the cell membrane. The released endocanabinoids are removed from the extracellular space through uptake and enzymatic degradation (Mechoulam et al, 1998). All these findings suggest that endocannabinoids can work as a diffusible and short-lived mediator that is released from activated neurons, binds to cannabinoid receptors on neighboring neurons to modulate their functions. Recent electrophysiological studies have revealed that endocannabinoids play an important role in retrograde modulation of synaptic transmission in the CNS (Kreitzer and Regehr, 2001b; Maejima et al, 2001a; Ohno-Shosaku et al, 2001; Wilson and NicoU, 2001). Endocannabinoids are released from postsynaptic neurons in response to either depolarization or activation of Gq/11-coupled receptors such as group I metabotropic glutamate receptors (mGluRs) and M1/M3 muscarinic acetylcholine receptors. The released endocannabinoids then activate presynaptic cannabinoid receptors and suppress transmitter release (Maejima et al, 2001b; Alger, 2002; Kano et al, 2002; Kreitzer and Regehr, 2002; Wilson and Nicoll, 2002; Freund et al, 2003; Kano et al., 2003; PiomelU, 2003). Thus, the endocannabinoid signaling is an important mechanism by which postsynaptic neuronal activity can retrogradely influence presynaptic functions. In this review, we introduce recent electrophysiological studies on endocannabinoidmediated retrograde modulation and discuss its possible physiological roles in the CNS.Dendritic neurotransmitter release, edited by Mike Ludwig, Springer, c2005, 269-281, (A part of the memoirs

Tuberous Sclerosis 2 Gene Is Expressed at High Levels in Specific Types of Neurons in the Mouse Brain

Tuberous sclerosis (TSC) is an autosomal dominant disorder characterized by mental retardation, epilepsy and hamartomatous growth in many tissues. The gene (TSC2) encoding a tumor suppressor protein whose mutations cause TSC, has been demonstrated to be expressed at high levels in the adult and developing brain, raising the question of whether or not the TSC2 gene product has unique roles in differentiation related to cytoskeletal interactions within the central nervous system, in addition to a tumor suppressor function. To determine the expression of TSC2 in functionally distinct neuron types of the mouse brain, we carried out in situ hybridization with digoxigenin-labeled riboprobes for the detection of TSC2 mRNA. High levels of the TSC2 gene were in neurons of the pyramidal and dentate granular layer in the hippocampus, cerebellar Purkinje cells, neurons of the piriform cortex, motor neurons in the medulla and interneurons in the striatum, while intermediate levels were in cortical neurons, striatal neurons, septal neurons, thalamic neurons and neurons in the substantia nigra compacta. Thus, the high expression of the TSC2 gene has restricted distribution in specific neuronal types which are characterized by well-developed dendrites and rich in use-dependent long-term changes in synaptic efficacy. These results suggest that the function of the TSC2 gene product may be involved on a cellular basis in neuronal plasticity and relevant to mental retardation observed in TSC patients

<Original>ESCA Study on Improvements in Adhesive Ability of Dental Adhesive Resin to Ni-Cr Alloy Treated by HNO_3 Solution

Ni-Cr合金を濃硝酸で処理すると研磨したままの場合よりも接着性レジン(4-META/MMA-TBB)に対する接着性が著しく向上する。その理由を解明するために硝酸処理と研磨したままの合金表面をX線光電子分光分析装置(ESCA)で分析し, 両者の表面構造を解析した。研磨したままでの合金表面におけるNiとCrの濃度は, Ni 21at%, Cr 17%であるが, 硝酸処理を施すとNi 13%, Cr 25%になった。硝酸処理によって合金表面で, 4-META レジンに対する親和性の劣るNiが減少し, 親和性の優れたCrが増加した。また, O 1sスペクトルを解析すると, 次の3つの酸素に由来する成分に分解された。成分Iは不動態被膜のCr-O-Crに由来する酸素, IIは不動態被膜中のCr-OH・・・H_2Oに由来する酸素, IIIは被膜上に存在する吸着水に由来する酸素である。これらの成分の存在比は, 研磨したままでは, II>I>IIIの順であるが, 硝酸処理では, 1>II>IIIになった。これらは, 硝酸処理によって, 4 -META レジンに対する接着性が優れている不動態被膜が強固に形成していることを示す。The adhesive ability of dental adhesive resin (4-META/MMA-TBB) to Ni-Cr alloy improves remarkably when the alloy surface is treated by cone. HNO_3 solution. Both as -polished and cone. HNO_3 treated alloy surfaces were analyzed by Electron Spectroscopy for Chemical Analysis (ESCA) to explain the superior adhesive ability of the alloy surface treated with HNO_3. The surface of the HNO_3 treated specimen contains 25 at % Cr and 13% Ni and the as -polished specimen contains 17% Cr and 21% Ni. It shows that Cr, which has a good chemical affinjty for 4-META resin, is concentrated on the alloy surface. The Q lg spectra can be separated into three components: Component I is due to oxygen bonded with chromium in the passive film, Cr-OCr; II is due to oxygen bonded with both chromium and hydrogen in the passive film, Cr-OH ・ ・ ・ OH_2; and III is due to oxygen in physisorbed water molecules on the passive film. The area fractions are in the order II>I>III for the as-polished surface and I>II>III for the HNO_3 treated surface, indicating that a firm passive structure is formed on the surface treated by HNO_3 solution. This is the cause of the increase in the adhesive ability of the 4-META resin on the passive film

The Quiescent Intracluster Medium in the Core of the Perseus Cluster

Clusters of galaxies are the most massive gravitationally-bound objects in the Universe and are still forming. They are thus important probes of cosmological parameters and a host of astrophysical processes. Knowledge of the dynamics of the pervasive hot gas, which dominates in mass over stars in a cluster, is a crucial missing ingredient. It can enable new insights into mechanical energy injection by the central supermassive black hole and the use of hydrostatic equilibrium for the determination of cluster masses. X-rays from the core of the Perseus cluster are emitted by the 50 million K diffuse hot plasma filling its gravitational potential well. The Active Galactic Nucleus of the central galaxy NGC1275 is pumping jetted energy into the surrounding intracluster medium, creating buoyant bubbles filled with relativistic plasma. These likely induce motions in the intracluster medium and heat the inner gas preventing runaway radiative cooling; a process known as Active Galactic Nucleus Feedback. Here we report on Hitomi X-ray observations of the Perseus cluster core, which reveal a remarkably quiescent atmosphere where the gas has a line-of-sight velocity dispersion of 164+/-10 km/s in a region 30-60 kpc from the central nucleus. A gradient in the line-of-sight velocity of 150+/-70 km/s is found across the 60 kpc image of the cluster core. Turbulent pressure support in the gas is 4% or less of the thermodynamic pressure, with large scale shear at most doubling that estimate. We infer that total cluster masses determined from hydrostatic equilibrium in the central regions need little correction for turbulent pressure.Comment: 31 pages, 11 Figs, published in Nature July

Hitomi (ASTRO-H) X-ray Astronomy Satellite

The Hitomi (ASTRO-H) mission is the sixth Japanese x-ray astronomy satellite developed by a large international collaboration, including Japan, USA, Canada, and Europe. The mission aimed to provide the highest energy resolution ever achieved at E  >  2  keV, using a microcalorimeter instrument, and to cover a wide energy range spanning four decades in energy from soft x-rays to gamma rays. After a successful launch on February 17, 2016, the spacecraft lost its function on March 26, 2016, but the commissioning phase for about a month provided valuable information on the onboard instruments and the spacecraft system, including astrophysical results obtained from first light observations. The paper describes the Hitomi (ASTRO-H) mission, its capabilities, the initial operation, and the instruments/spacecraft performances confirmed during the commissioning operations for about a month

Hitomi X-Ray Studies of Giant Radio Pulses from the Crab Pulsar

To search for giant X-ray pulses correlated with the giant radio pulses (GRPs) from the Crab pulsar, we performed a simultaneous observation of the Crab pulsar with the X-ray satellite Hitomi in the 2300 keV band and the Kashima NICT radio telescope in the 1.41.7 GHz band with a net exposure of about 2 ks on 2016 March 25, just before the loss of the Hitomi mission. The timing performance of the Hitomi instruments was confirmed to meet the timing requirement and about 1000 and 100 GRPs were simultaneously observed at the main pulse and inter-pulse phases, respectively, and we found no apparent correlation between the giant radio pulses and the X-ray emission in either the main pulse or inter-pulse phase. All variations are within the 2 fluctuations of the X-ray fluxes at the pulse peaks, and the 3 upper limits of variations of main pulse or inter-pulse GRPs are 22% or 80% of the peak flux in a 0.20 phase width, respectively, in the 2300 keV band. The values for main pulse or inter-pulse GRPs become 25% or 110%, respectively, when the phase width is restricted to the 0.03 phase. Among the upper limits from the Hitomi satellite, those in the 4.510 keV and 70300 keV bands are obtained for the first time, and those in other bands are consistent with previous reports. Numerically, the upper limits of the main pulse and inter-pulse GRPs in the 0.20 phase width are about (2.4 and 9.3) 10(exp 11) erg cm(exp 2), respectively. No significant variability in pulse profiles implies that the GRPs originated from a local place within the magnetosphere. Although the number of photon-emitting particles should temporarily increase to account for the brightening of the radio emission, the results do not statistically rule out variations correlated with the GRPs, because the possible X-ray enhancement may appear due to a >0.02% brightening of the pulse-peak flux under such conditions

Effect of clinical signs, endocrinopathies, timing of surgery, hyperlipidemia, and hyperbilirubinemia on outcome in dogs with gallbladder mucocele

Gallbladder mucocele (GBM) is a common extra-hepatic biliary syndrome in dogs with death rates ranging from 7 to 45%. Therefore, the aim of this study was to identify the association of survival with variables that could be utilized to improve clinical decisions. A total of 1194 dogs with a gross and histopathological diagnosis of GBM were included from 41 veterinary referral hospitals in this retrospective study. Dogs with GBM that demonstrated abnormal clinical signs had significantly greater odds of death than subclinical dogs in a univariable analysis (OR, 4.2; 95% CI, 2.14–8.23; P < 0.001). The multivariable model indicated that categorical variables including owner recognition of jaundice (OR, 2.12; 95% CI, 1.19–3.77; P = 0.011), concurrent hyperadrenocorticism (OR 1.94; 95% CI, 1.08–3.47; P = 0.026), and Pomeranian breed (OR, 2.46; 95% CI 1.10–5.50; P = 0.029) were associated with increased odds of death, and vomiting was associated with decreased odds of death (OR, 0.48; 95% CI, 0.30–0.72; P = 0.001). Continuous variables in the multivariable model, total serum/plasma bilirubin concentration (OR, 1.03; 95% CI, 1.01–1.04; P < 0.001) and age (OR, 1.17; 95% CI, 1.08–1.26; P < 0.001), were associated with increased odds of death. The clinical utility of total serum/plasma bilirubin concentration as a biomarker to predict death was poor with a sensitivity of 0.61 (95% CI, 0.54–0.69) and a specificity of 0.63 (95% CI, 0.59–0.66). This study identified several prognostic variables in dogs with GBM including total serum/plasma bilirubin concentration, age, clinical signs, concurrent hyperadrenocorticism, and the Pomeranian breed. The presence of hypothyroidism or diabetes mellitus did not impact outcome in this study.Supplemental Table S1. Number of dogs included from each institution and years reviewed.Supplemental Table S2. Included breeds.Supplemental Table S3. Distribution of various reasons given for performing cholecystectomy in the 179 subclinical dogs with gallbladder mucocele (GBM).Supplemental Table S4. Distribution of clinical signs associated with systemic illness in 982 dogs with gallbladder mucocele.Supplemental Table S5. Distribution of reasons for death in-hospital (i.e. euthanized and died) in 179 dogs with gallbladder mucocele that underwent cholecystectomy.http://www.elsevier.com/locate/tvjlhj2020Companion Animal Clinical Studie