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Sample records for d2 na morbidade

  1. Plant Defensins NaD1 and NaD2 Induce Different Stress Response Pathways in Fungi

    PubMed Central

    Dracatos, Peter M.; Payne, Jennifer; Di Pietro, Antonio; Anderson, Marilyn A.; Plummer, Kim M.

    2016-01-01

    Nicotiana alata defensins 1 and 2 (NaD1 and NaD2) are plant defensins from the ornamental tobacco that have antifungal activity against a variety of fungal pathogens. Some plant defensins interact with fungal cell wall O-glycosylated proteins. Therefore, we investigated if this was the case for NaD1 and NaD2, by assessing the sensitivity of the three Aspergillus nidulans (An) O-mannosyltransferase (pmt) knockout (KO) mutants (An∆pmtA, An∆pmtB, and An∆pmtC). An∆pmtA was resistant to both defensins, while An∆pmtC was resistant to NaD2 only, suggesting NaD1 and NaD2 are unlikely to have a general interaction with O-linked side chains. Further evidence of this difference in the antifungal mechanism was provided by the dissimilarity of the NaD1 and NaD2 sensitivities of the Fusarium oxysporum f. sp. lycopersici (Fol) signalling knockout mutants from the cell wall integrity (CWI) and high osmolarity glycerol (HOG) mitogen-activated protein kinase (MAPK) pathways. HOG pathway mutants were sensitive to both NaD1 and NaD2, while CWI pathway mutants only displayed sensitivity to NaD2. PMID:27598152

  2. Ro-vibrational Stark effect on H2 and D2 molecules adsorbed in NaA zeolite

    NASA Astrophysics Data System (ADS)

    Bras, N.

    1999-03-01

    In order to explain the induced infrared bands of H2 and D2 adsorbed in NaA zeolites the Stark effect on the ro-vibrational levels of these molecules is considered for electric fields created by various charge distributions. The shift and intensity of the induced ro-vibration transitions are calculated.

  3. Flare line impact polarization. Na D2 589 nm line polarization in the 2001 June 15 flare

    NASA Astrophysics Data System (ADS)

    Hénoux, J. C.; Karlický, M.

    2013-08-01

    Context. The impact polarization of optical chromospheric lines in solar flares is still being debated. For this reason, additional observations and improved flare atmosphere models are needed still. Aims: The polarization-free telescope THEMIS used in multiline 2 MulTiRaies (MTR) mode allows accurate simultaneous linear polarization measurements in various spectral lines. Methods: In the 2001 June 15 flare, Hα, Hβ, and Mg D2 lines linear impact polarization was reported as present in THEMIS 2 MTR observations. In this paper, THEMIS data analysis was extended to the Na D2 line. Sets of I ± U and I ± Q flare Stokes S 2D-spectra were corrected from dark-current, spectral-line curvature and from transmission differences. Then, we derived the linear polarization degree P and polarization orientation angle α 2D-spectra. No change in relative positioning could be found that would reduce the Stokes parameters U and Q values. No V and I crosstalks could explain our results either. Results: The Na D2 line is linearly polarized with a polarization degree exceeding 5% at some locations. The polarization was found to be radial at outer ribbons edges, and tangential at their inner edges. This orientation change may be due to differences in electron distribution functions on the opposite borders of flare chromospheric ribbons. Electron beams propagating along magnetic field lines, together with return currents, could explain both radial and tangential polarization. At the inner ribbon edges, intensity profile-width enlargements and blueshifts in polarization profiles are observed. This suggests chromospheric evaporation. Appendix A is available in electronic form at http://www.aanda.org

  4. Dopamine on D2-like receptors is involved in reward evaluation in water-deprived rats licking for NaCl and water.

    PubMed

    Canu, Maria Elena; Carta, Davide; Murgia, Emanuele; Serra, Gino; D'Aquila, Paolo S

    2010-08-01

    The analysis of licking microstructure provides measures, size and number of licking bouts, which might reveal, respectively, reward evaluation and behavioural activation. Based on the ability of the dopamine D2-like receptor antagonist raclopride to reduce bout size and to induce an "extinction mimicry effect" on bout number, we suggested that the level of activation of reward-associated responses is updated, or "reboosted", on the basis of a dopamine D2-like receptor-mediated evaluation process occurring during the consummatory transaction with the reward. Here we investigate the effects of the dopamine D2-like receptor antagonist raclopride (0, 25, 125, and 250microg/kg) on the microstructure of licking for water and sodium chloride solutions (0.075M, 0.15M, and 0.3M) in 12h water-deprived rats. In each session, rats were exposed to brief contact tests (1min) for each solution. Bout size, but not bout number, was decreased at the highest NaCl concentration. Raclopride reduced lick number owing to reduced bout size, while bout number was either not affected or even increased depending on the dose. These results are in agreement with the previous observations on sucrose licking, and suggest the involvement of dopamine D2-like receptors in an evaluation process occurring during the consummatory transaction with the reward.

  5. Isolation and Characterization of ScGluD2, a New Sugarcane beta-1,3-Glucanase D Family Gene Induced by Sporisorium scitamineum, ABA, H2O2, NaCl, and CdCl2 Stresses

    PubMed Central

    Su, Yachun; Wang, Zhuqing; Liu, Feng; Li, Zhu; Peng, Qiong; Guo, Jinlong; Xu, Liping; Que, Youxiong

    2016-01-01

    Beta-1,3-glucanases (EC 3.2.1.39), commonly known as pathogenesis-related (PR) proteins, play an important role not only in plant defense against fungal pathogens but also in plant physiological and developmental processes. However, only a limited number of sugarcane beta-1,3-glucanase genes have been isolated. In the present study, we identified and characterized a new beta-1,3-glucanase gene ScGluD2 (GenBank Acc No. KF664181) from sugarcane. An X8 domain was present at the C terminal region of ScGluD2, suggesting beta-1,3-glucan-binding function. Phylogenetic analysis showed that the predicted ScGluD2 protein was classified into subfamily D beta-1,3-glucanase. Localization of the ScGluD2 protein in the plasma membrane was determined by tagging it with green fluorescent protein. The expression of ScGluD2 was more up-regulated in sugarcane smut-resistant cultivars in the early stage (1 or 3 days) than in the susceptible ones after being challenged by the smut pathogen, revealing that ScGluD2 may be involved in defense against the invasion of Sporisorium scitamineum. Transient overexpression of ScGluD2 in Nicotiana benthamiana leaves induced a defense response and exhibited antimicrobial action on the tobacco pathogens Pseudomonas solanacearum and Botrytis cinerea, further demonstrating that ScGluD2 was related to the resistance to plant pathogens. However, the transcripts of ScGluD2 partially increased (12 h) under NaCl stress, and were steadily up-regulated from 6 to 24 h upon ABA, H2O2, and CdCl2 treatments, suggesting that ABA may be a signal molecule regulating oxidative stress and play a role in the salt and heavy metal stress-induced stimulation of ScGluD2 transcripts. Taken together, ScGluD2, a novel member of subfamily D beta-1,3-glucanase, was a stress-related gene of sugarcane involved in plant defense against smut pathogen attack and salt and heavy metal stresses. PMID:27642288

  6. Calculation of the fundamental vibrational frequencies and intensities of H2, D2, and N2 in the presence of Li(+) or Na

    NASA Astrophysics Data System (ADS)

    Bishop, David M.; Cybulski, Slawomir M.

    1994-11-01

    Self-consistent-field (SCF) and second-order Moller-Plesset (MP2) calculations, using large basis sets, have been carried out for the system X2...Y(+), with X = H, D, and N and Y = Li and Na. In particular, the fundamental vibrational frequency shifts and intensities induced in the diatomic by the cation have been found. For Y = Na these properties may be compared with the experimental infrared spectra of the same diatomics when trapped in a NaA zeolite. There is good agreement between theory and experiment for the frequency shifts but the calculated intensity for N2...Na(+) is several times larger than that found in the zeolite. This indicates that either the model for the trapped species is too simple or the experimental result needs reassessment.

  7. Adsorption and coadsorption of molecular hydrogen isotopes in zeolites. II. Infrared analyses of H2, HD, and D2 in NaA

    NASA Astrophysics Data System (ADS)

    Stéphanie-Victoire, Françoise; de Lara, Evelyne Cohen

    1998-10-01

    The infrared analysis of the induced bands of molecular hydrogen isotopes, adsorbed in NaA zeolite, shows several features; (i) when the amount of adsorbed molecules increases, the bands become complex, showing three components, which can be related to different energetic situation of the molecules in the cavity; (ii) the band frequency is lower than the gas frequency; for each species the shifts are proportional to the inverse square root of the mass (same interaction with the crystal); (iii) the absolute intensity increases when the temperature decreases, this is due to the fact that the molecule remains longer in the vicinity of the adsorption site where the electric field is the highest. Its amplitude is deduced from the absolute intensities measured at the lowest temperature (˜1010 V/m, in agreement with other results).

  8. Master equation theory applied to the redistribution of polarized radiation in the weak radiation field limit. IV. Application to the second solar spectrum of the Na i D1 and D2 lines

    NASA Astrophysics Data System (ADS)

    Bommier, Véronique

    2016-06-01

    Context. The spectrum of the linear polarization, which is formed by scattering and observed on the solar disk close to the limb, is very different from the intensity spectrum and thus able to provide new information, in particular about anisotropies in the solar surface plasma and magnetic fields. In addition, a large number of lines show far wing polarization structures assigned to partial redistribution (PRD), which we prefer to denote as Rayleigh/Raman scattering. The two-level or two-term atom approximation without any lower level polarization is insufficient for many lines. Aims: In the previous paper of this series, we presented our theory generalized to the multilevel and multiline atom and comprised of statistical equilibrium equations for the atomic density matrix elements and radiative transfer equation for the polarized radiation. The present paper is devoted to applying this theory to model the second solar spectrum of the Na i D1 and D2 lines. Methods: The solution method is iterative, of the lambda-iteration type. The usual acceleration techniques were considered or even applied, but we found these to be unsuccessful, in particular because of nonlinearity or large number of quantities determining the radiation at each depth. Results: The observed spectrum is qualitatively reproduced in line center, but the convergence is yet to be reached in the far wings and the observed spectrum is not totally reproduced there. Conclusions: We need to investigate noniterative resolution methods. The other limitation lies in the one-dimensional (1D) atmosphere model, which is unable to reproduce the intermittent matter structure formed of small loops or spicules in the chromosphere. This modeling is rough, but the computing time in the presence of hyperfine structure and PRD prevents us from envisaging a three-dimensional (3D) model at this instant.

  9. D2PC sensitivity analysis

    SciTech Connect

    Lombardi, D.P.

    1992-08-01

    The Chemical Hazard Prediction Model (D2PC) developed by the US Army will play a critical role in the Chemical Stockpile Emergency Preparedness Program by predicting chemical agent transport and dispersion through the atmosphere after an accidental release. To aid in the analysis of the output calculated by D2PC, this sensitivity analysis was conducted to provide information on model response to a variety of input parameters. The sensitivity analysis focused on six accidental release scenarios involving chemical agents VX, GB, and HD (sulfur mustard). Two categories, corresponding to conservative most likely and worst case meteorological conditions, provided the reference for standard input values. D2PC displayed a wide variety of sensitivity to the various input parameters. The model displayed the greatest overall sensitivity to wind speed, mixing height, and breathing rate. For other input parameters, sensitivity was mixed but generally lower. Sensitivity varied not only with parameter, but also over the range of values input for a single parameter. This information on model response can provide useful data for interpreting D2PC output.

  10. D2 Inertial Measurement Unit

    NASA Astrophysics Data System (ADS)

    Dewar, Patrick; Gido, Joseph; Carroll, Joseph

    1993-06-01

    The D2 Hypervelocity Projectile is a Strategic Defense Initiative sponsored technology program that is designed to provide low endo-atmospheric, kinetic kill defense against strategic reentry vehicles. The D2 program is funded through the U.S. Army Space and Strategic Defense Command (SSDC) in Huntsville, AL and contracted through the U.S. Army Armament Research and Development Engineering Center (ARDEC) at Picatinny Arsenal, NJ. In GFY 93 the program began an integration and flight demonstration phase with the Hypervelocity Fire Control System (HVFC) and the Solid Propellant Electro Thermal Chemical (SPETC) launcher. The Inertial Measurement Unit (IMU) necessary to perform the autopilot and guidance data gathering must be extremely small, lightweight and shock hardened. The IMU is comprised of three Honeywell GG1308 miniature Ring Laser Gyros (RLG), and three Endevco 7290-M19 miniature silicon accelerometers. The IMU has self-contained high voltage Power Supply (HVPS) processor and memory electronics providing a complete stand alone, three axis measurement package. This Inertial Cluster Assembly (ICA) is then packaged into a cylindrical housing, approximately 1.9 inches in diameter and 1.3 inches in length.

  11. Identification of D-2 dopaminergic receptors in bovine adrenal cortex

    SciTech Connect

    Missale, C.; Liberini, P.; Memo, M.; Carruba, M.O.; Spano, P.

    1985-12-30

    Dopamine receptors in bovine adrenal cortex have been studied by using /sup 3/H-(-) atsulpiride as selective ligand. The specific binding is saturable and the Scatchard analysis reveals a single component with a Kd of 6.2 nM and a Bmax of 8 fmoles/mg protein. The characterization indicates that the binding is rapid, reversible, stereospecific, Na/sup +/ - and temperature-dependent. Moreover its pharmacological profile is superimposable to that of D-2 receptors in the striatum, thus suggesting that central and peripheral D-2 receptors are identical. 27 references, 6 figures, 1 table.

  12. 7 CFR 15d.2 - Discrimination prohibited.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 1 2014-01-01 2014-01-01 false Discrimination prohibited. 15d.2 Section 15d.2... THE UNITED STATES DEPARTMENT OF AGRICULTURE § 15d.2 Discrimination prohibited. (a) No agency, officer... participation in, deny the benefits of, or subject to discrimination any person in the United States under...

  13. 7 CFR 15d.2 - Discrimination prohibited.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 1 2011-01-01 2011-01-01 false Discrimination prohibited. 15d.2 Section 15d.2... THE UNITED STATES DEPARTMENT OF AGRICULTURE § 15d.2 Discrimination prohibited. (a) No agency, officer... participation in, deny the benefits of, or subject to discrimination any person in the United States under...

  14. 7 CFR 15d.2 - Discrimination prohibited.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 1 2012-01-01 2012-01-01 false Discrimination prohibited. 15d.2 Section 15d.2... THE UNITED STATES DEPARTMENT OF AGRICULTURE § 15d.2 Discrimination prohibited. (a) No agency, officer... participation in, deny the benefits of, or subject to discrimination any person in the United States under...

  15. 7 CFR 15d.2 - Discrimination prohibited.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Discrimination prohibited. 15d.2 Section 15d.2... THE UNITED STATES DEPARTMENT OF AGRICULTURE § 15d.2 Discrimination prohibited. (a) No agency, officer... participation in, deny the benefits of, or subject to discrimination any person in the United States under...

  16. Distinct regulation of dopamine D2S and D2L autoreceptor signaling by calcium

    PubMed Central

    Gantz, Stephanie C; Robinson, Brooks G; Buck, David C; Bunzow, James R; Neve, Rachael L; Williams, John T; Neve, Kim A

    2015-01-01

    D2 autoreceptors regulate dopamine release throughout the brain. Two isoforms of the D2 receptor, D2S and D2L, are expressed in midbrain dopamine neurons. Differential roles of these isoforms as autoreceptors are poorly understood. By virally expressing the isoforms in dopamine neurons of D2 receptor knockout mice, this study assessed the calcium-dependence and drug-induced plasticity of D2S and D2L receptor-dependent G protein-coupled inwardly rectifying potassium (GIRK) currents. The results reveal that D2S, but not D2L receptors, exhibited calcium-dependent desensitization similar to that exhibited by endogenous autoreceptors. Two pathways of calcium signaling that regulated D2 autoreceptor-dependent GIRK signaling were identified, which distinctly affected desensitization and the magnitude of D2S and D2L receptor-dependent GIRK currents. Previous in vivo cocaine exposure removed calcium-dependent D2 autoreceptor desensitization in wild type, but not D2S-only mice. Thus, expression of D2S as the exclusive autoreceptor was insufficient for cocaine-induced plasticity, implying a functional role for the co-expression of D2S and D2L autoreceptors. DOI: http://dx.doi.org/10.7554/eLife.09358.001 PMID:26308580

  17. Hypothyroidism affects D2 receptor-mediated breathing without altering D2 receptor expression.

    PubMed

    Schlenker, Evelyn H; Del Rio, Rodrigo; Schultz, Harold D

    2014-03-01

    Bromocriptine depressed ventilation in air and D2 receptor expression in the nucleus tractus solitaries (NTS) in male hypothyroid hamsters. Here we postulated that in age-matched hypothyroid female hamsters, the pattern of D2 receptor modulation of breathing and D2 receptor expression would differ from those reported in hypothyroid males. In females hypothyroidism did not affect D2 receptor protein levels in the NTS, carotid bodies or striatum. Bromocriptine, but not carmoxirole (a peripheral D2 receptor agonist), increased oxygen consumption and body temperature in awake air-exposed hypothyroid female hamsters and stimulated their ventilation before and following exposure to hypoxia. Carmoxirole depressed frequency of breathing in euthyroid hamsters prior to, during and following hypoxia exposures and stimulated it in the hypothyroid hamsters following hypoxia. Although hypothyroidism did not affect expression of D2 receptors, it influenced central D2 modulation of breathing in a disparate manner relative to euthyroid hamsters.

  18. THz spectroscopy of D2H+

    NASA Astrophysics Data System (ADS)

    Yu, S.; Pearson, J. C.; Amano, T.; Matsushima, F.

    2017-01-01

    We extended the measurements of the rotational transitions of D2H+ up to 3 THz by using the JPL frequency multiplier chains and a TuFIR system at Toyama. D2H+ was generated in an extended negative glow discharge cell cooled to liquid nitrogen temperature. We observed five new THz lines. All the available rotational transition frequencies together with the combination differences derived from the three fundamental bands were subject to least square analysis to determine the molecular constants. New THz measurements are definitely useful for better characterization of spectroscopic properties. The improved molecular constants provide better predictions of other unobserved rotational transitions.

  19. 7 CFR 15d.2 - Discrimination prohibited.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... THE UNITED STATES DEPARTMENT OF AGRICULTURE § 15d.2 Discrimination prohibited. (a) No agency, officer, or employee of the United States Department of Agriculture shall, on the ground of race, color... program or activity conducted by the United States Department of Agriculture. (b) No person shall...

  20. 42 CFR 52d.2 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL CANCER INSTITUTE CLINICAL CANCER EDUCATION PROGRAM § 52d.2 Definitions. (a) Act means the Public Health Service Act, as amended. (b) Director, NCI, means the Director of the National Cancer Institute and any other officer or employee...

  1. 42 CFR 52d.2 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL CANCER INSTITUTE CLINICAL CANCER EDUCATION PROGRAM § 52d.2 Definitions. (a) Act means the Public Health Service Act, as amended. (b) Director, NCI, means the Director of the National Cancer Institute and any other officer or employee...

  2. 42 CFR 52d.2 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL CANCER INSTITUTE CLINICAL CANCER EDUCATION PROGRAM § 52d.2 Definitions. (a) Act means the Public Health Service Act, as amended. (b) Director, NCI, means the Director of the National Cancer Institute and any other officer or employee...

  3. 42 CFR 52d.2 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL CANCER INSTITUTE CLINICAL CANCER EDUCATION PROGRAM § 52d.2 Definitions. (a) Act means the Public Health Service Act, as amended. (b) Director, NCI, means the Director of the National Cancer Institute and any other officer or employee...

  4. 42 CFR 52d.2 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GRANTS NATIONAL CANCER INSTITUTE CLINICAL CANCER EDUCATION PROGRAM § 52d.2 Definitions. (a) Act means the Public Health Service Act, as amended. (b) Director, NCI, means the Director of the National Cancer Institute and any other officer or employee...

  5. Neptune's small dark spot (D2)

    NASA Technical Reports Server (NTRS)

    1999-01-01

    This bulls-eye view of Neptune's small dark spot (D2) was obtained by Voyager 2's narrow-angle camera. Banding surrounding the feature indicates unseen strong winds, while structures within the bright spot suggest both active upwelling of clouds and rotation about the center. A rotation rate has not yet been measured, but the V-shaped structure near the right edge of the bright area indicates that the spot rotates clockwise. Unlike the Great Red Spot on Jupiter, which rotates counterclockwise, if the D2 spot on Neptune rotates clockwise, the material will be descending in the dark oval region. The fact that infrared data will yield temperature information about the region above the clouds makes this observation especially valuable. The Voyager Mission is conducted by JPL for NASA's Office of Space Science and Applications.

  6. Time resolved spectroscopic investigation of SiD2 + D2: kinetic study

    NASA Astrophysics Data System (ADS)

    Al-Rubaiey, Najem A.; Walsh, Robin

    2017-03-01

    Silylenes (silanediyls) have made an important impact on organosilicon chemistry even if it is of more recent foundation than carbenes in organic chemistry and much less complete. These species are highly reactive intermediates. They play a central role in the chemical vapour deposition (CVD) of various silicon-containing thin films which have a technological importance in microelectronics as well as in the dry etching processes of silicon wafers. Spectroscopic methods have been developed to observe these species, a necessary pre-requisite to their direct monitoring. In this work, deuterated phenylsilane precursor, PhSiD3 was chosen for SiD2 because its analogue phenylsilane, PhSiH3 proved to be a good precursor for SiH2 and the high quality decay signals observed revealed that SiD2 be readily detected from PhSiD3 and that if other decomposition pathways (e.g. PhSiD + D2) are occurring, they do not effect measurements of the rate constants for SiD2. The absorption spectrum of SiD2 formed from the flash photolysis of a mixture of PhSiD3 and SF6 at 193nm were found in the region 17384-17391 cm-1 with strong band at 17387.07 cm-1. This single rotational line of pQ1 was chosen to monitor SiD2 removal. Time-resolved studies of SiD2 have been carried out to obtain rate constants for its bimolecular reactions with D2. The reactions were studied over the pressure range 5-100 Torr (in SF6 bath gas) at four temperatures in the range 298-498K. Single decay from 10 photolysis laser shots were averaged and found to give reasonable first-order kinetics fits. Second order kinetics were obtained by pressure dependence of the pseudo first order decay constants and substance D2 pressures within experimental error. The reaction was found to be weakly pressure dependent at all temperatures, consistent with a third-body mediated association process. In addition, SiH2+ H2 reaction is approximately ca. 60% faster than SiD2+D2 reaction. Theoretical extrapolations (using Lindemann

  7. Cauchy Conformal Fields in Dimensions {d > 2}

    NASA Astrophysics Data System (ADS)

    Friedan, Daniel; Keller, Christoph A.

    2016-12-01

    Holomorphic fields play an important role in 2d conformal field theory. We generalize them to {d > 2} by introducing the notion of Cauchy conformal fields, which satisfy a first order differential equation such that they are determined everywhere once we know their value on a codimension 1 surface. We classify all the unitary Cauchy fields. By analyzing the mode expansion on the unit sphere, we show that all unitary Cauchy fields are free in the sense that their correlation functions factorize on the 2-point function. We also discuss the possibility of non-unitary Cauchy fields and classify them in d = 3 and 4.

  8. 21 CFR 172.379 - Vitamin D2.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 3 2012-04-01 2012-04-01 false Vitamin D2. 172.379 Section 172.379 Food and Drugs... Dietary and Nutritional Additives § 172.379 Vitamin D2. Vitamin D2 may be used safely in foods as a... prescribed conditions: (a) Vitamin D2, also known as ergocalciferol, is the chemical...

  9. 21 CFR 172.379 - Vitamin D2.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 3 2011-04-01 2011-04-01 false Vitamin D2. 172.379 Section 172.379 Food and Drugs... Dietary and Nutritional Additives § 172.379 Vitamin D2. Vitamin D2 may be used safely in foods as a... prescribed conditions: (a) Vitamin D2, also known as ergocalciferol, is the chemical...

  10. 21 CFR 172.379 - Vitamin D2.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Vitamin D2. 172.379 Section 172.379 Food and Drugs... Dietary and Nutritional Additives § 172.379 Vitamin D2. Vitamin D2 may be used safely in foods as a... prescribed conditions: (a) Vitamin D2, also known as ergocalciferol, is the chemical...

  11. 21 CFR 172.379 - Vitamin D2.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Vitamin D2. 172.379 Section 172.379 Food and Drugs... Dietary and Nutritional Additives § 172.379 Vitamin D2. Vitamin D2 may be used safely in foods as a... prescribed conditions: (a) Vitamin D2, also known as ergocalciferol, is the chemical...

  12. Dopamine D2High receptors stimulated by phencyclidines, lysergic acid diethylamide, salvinorin A, and modafinil.

    PubMed

    Seeman, Philip; Guan, Hong-Chang; Hirbec, Hélène

    2009-08-01

    Although it is commonly stated that phencyclidine is an antagonist at ionotropic glutamate receptors, there has been little measure of its potency on other receptors in brain tissue. Although we previously reported that phencyclidine stimulated cloned-dopamine D2Long and D2Short receptors, others reported that phencyclidine did not stimulate D2 receptors in homogenates of rat brain striatum. This study, therefore, examined whether phencyclidine and other hallucinogens and psychostimulants could stimulate the incorporation of [(35)S]GTP-gamma-S into D2 receptors in homogenates of rat brain striatum, using the same conditions as previously used to study the cloned D2 receptors. Using 10 microM dopamine to define 100% stimulation, phencyclidine elicited a maximum incorporation of 46% in rat striata, with a half-maximum concentration of 70 nM for phencyclidine, when compared with 80 nM for dopamine, 89 nM for salvinorin A (48 nM for D2Long), 105 nM for lysergic acid diethylamide (LSD), 120 nM for R-modafinil, 710 nM for dizocilpine, 1030 nM for ketamine, and >10,000 nM for S-modafinil. These compounds also inhibited the binding of the D2-selective ligand [(3)H]domperidone. The incorporation was inhibited by the presence of 200 microM guanylylimidodiphosphate and also by D2 blockade, using 10 microM S-sulpiride, but not by D1 blockade with 10 microM SCH23390. Hypertonic buffer containing 150 mM NaCl inhibited the stimulation by phencyclidine, which may explain negative results by others. It is concluded that phencyclidine and other psychostimulants and hallucinogens can stimulate dopamine D2 receptors at concentrations related to their behavioral actions.

  13. Binding Interactions of Dopamine and Apomorphine in D2High and D2Low States of Human Dopamine D2 Receptor Using Computational and Experimental Techniques.

    PubMed

    Durdagi, Serdar; Salmas, Ramin Ekhteiari; Stein, Matthias; Yurtsever, Mine; Seeman, Philip

    2016-02-17

    We have recently reported G-protein coupled receptor (GPCR) model structures for the active and inactive states of the human dopamine D2 receptor (D2R) using adrenergic crystal structures as templates. Since the therapeutic concentrations of dopamine agonists that suppress the release of prolactin are the same as those that act at the high-affinity state of the D2 receptor (D2High), D2High in the anterior pituitary gland is considered to be the functional state of the receptor. In addition, the therapeutic concentrations of anti-Parkinson drugs are also related to the dissociation constants in the D2High form of the receptor. The discrimination between the high- and low-affinity (D2Low) components of the D2R is not obvious and requires advanced computer-assisted structural biology investigations. Therefore, in this work, the derived D2High and D2Low receptor models (GPCR monomer and dimer three-dimensional structures) are used as drug-binding targets to investigate binding interactions of dopamine and apomorphine. The study reveals a match between the experimental dissociation constants of dopamine and apomorphine at their high- and low-affinity sites of the D2 receptor in monomer and dimer and their calculated dissociation constants. The allosteric receptor-receptor interaction for dopamine D2R dimer is associated with the accessibility of adjacent residues of transmembrane region 4. The measured negative cooperativity between agonist ligand at dopamine D2 receptor is also correctly predicted using the D2R homodimerization model.

  14. 21 CFR 172.381 - Vitamin D2 bakers yeast.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 3 2013-04-01 2013-04-01 false Vitamin D2 bakers yeast. 172.381 Section 172.381... CONSUMPTION Special Dietary and Nutritional Additives § 172.381 Vitamin D2 bakers yeast. Vitamin D2 bakers yeast may be used safely in foods as a source of vitamin D2 and as a leavening agent in accordance...

  15. 21 CFR 172.379 - Vitamin D2.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Vitamin D2. 172.379 Section 172.379 Food and Drugs....379 Vitamin D2. Vitamin D2 may be used safely in foods as a nutrient supplement defined under § 170.3(o)(20) of this chapter in accordance with the following prescribed conditions: (a) Vitamin D2,...

  16. 21 CFR 172.381 - Vitamin D2 bakers yeast.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 3 2014-04-01 2014-04-01 false Vitamin D2 bakers yeast. 172.381 Section 172.381... Additives § 172.381 Vitamin D2 bakers yeast. Vitamin D2 bakers yeast may be used safely in foods as a source of vitamin D2 and as a leavening agent in accordance with the following prescribed conditions:...

  17. 21 CFR 582.5950 - Vitamin D 2.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Vitamin D 2. 582.5950 Section 582.5950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5950 Vitamin D 2. (a) Product. Vitamin D2. (b) Conditions of use. This substance...

  18. 21 CFR 582.5950 - Vitamin D2.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Vitamin D2. 582.5950 Section 582.5950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5950 Vitamin D2. (a) Product. Vitamin D2. (b) Conditions of use. This substance is...

  19. 21 CFR 582.5950 - Vitamin D2.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Vitamin D2. 582.5950 Section 582.5950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5950 Vitamin D2. (a) Product. Vitamin D2. (b) Conditions of use. This substance is...

  20. 21 CFR 582.5950 - Vitamin D 2.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Vitamin D 2. 582.5950 Section 582.5950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5950 Vitamin D 2. (a) Product. Vitamin D2. (b) Conditions of use. This substance...

  1. 21 CFR 582.5950 - Vitamin D2.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Vitamin D2. 582.5950 Section 582.5950 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS... 1 § 582.5950 Vitamin D2. (a) Product. Vitamin D2. (b) Conditions of use. This substance is...

  2. Dynamic quantum molecular sieving separation of D2 from H2-D2 mixture with nanoporous materials.

    PubMed

    Niimura, Subaru; Fujimori, Toshihiko; Minami, Daiki; Hattori, Yoshiyuki; Abrams, Lloyd; Corbin, Dave; Hata, Kenji; Kaneko, Katsumi

    2012-11-14

    Quantum molecular sieving separability of D(2) from an H(2)-D(2) mixture was measured at 77 K for activated carbon fiber, carbon molecular sieve, zeolite and single wall carbon nanotube using a flow method. The amount of adsorbed D(2) was evidently larger than H(2) for all samples. The maximum adsorption ratio difference between D(2) and H(2) was 40% for zeolite (MS13X), yielding a selectivity for D(2) with respect to H(2) of 3.05.

  3. Interactions of D2O with methane and fluoromethane surfaces.

    PubMed

    Souda, R; Kawanowa, H; Kondo, M; Gotoh, Y

    2004-03-22

    TOF-SIMS is used to investigate the interactions between D2O and hydrophobic molecules, such as CH4, CH3F, CH2F2, CHF3, and CF4, at cryogenic temperatures (15 K). By irradiation with a 1.5-keV He+ beam, the D(+)(D2O)n ions are ejected efficiently from the D2O nanoclusters physisorbed on the CF4 layer due to Coulomb explosion: the ion yields are by about two orders of magnitude higher than those from a thick D2O layer via the kinetic sputtering. The D(+)(D2O)n yields decrease on the CHnF(4-n) layer with increasing the number of the C-H group. This is because the Coulombic fission is quenched due to the delocalization of valence holes through the C-H...H-C and C-H...D2O contacts. A pure D2O film is hardly grown on the CH4 layer as a consequence of intermixing whereas the D2O molecules basically adsorb on the surfaces of fluoromethanes, suggesting the attractive (water-repellent) interactions in the C-H...D2O (C-F...D2O) contacts. The C-H...O bond behaves like a conventional O-H...O hydrogen bond as far as the collision-induced proton transfer reaction is concerned.

  4. West Valley Tank 8D-1 and 8D-2 Inventory Estimation Methodology

    SciTech Connect

    O'Brien, Robert F.; Heasler, Patrick G.; Rowell, Laurene

    2001-07-20

    This report details work funded by the West Valley Support Project (WVSP) and the Tanks Focus Area Retrieval and Closure Program. The work was conducted by the Pacific Northwest National Laboratory (PNNL) and is in support of the West Valley Demonstration Project (WVDP). The WVDP site in New York was originally the site of a commercial nuclear fuel reprocessing plant. The high-level waste (HLW), approximately 2 million liters, produced during plutonium-uranium extraction (PUREX) and thorium extraction (THOREX) reprocessing campaigns at the plant and subsequent HLW preprocessing, was stored on site in three tanks identified as 8D-1, 8D-2, and 8D-4. Waste from the PUREX process was neutralized with NaOH for storage in a carbon steel tank designated as 8D-2. Neutralization resulted in a precipitated hydroxide sludge that settled to the bottom of the tank and was covered by a supernatant salt solution. The acidic THOREX waste, approximately 55,000 L, was first stored in a stainless steel tank (8D-4) and then added to the PUREX waste in Tank 8D-2. Supernatant decontamination, primarily cesium removal, was conducted by ion-exchange using in-tank columns suspended in Tank 8D-1. The cesium-loaded zeolite, resulting from the supernatant decontamination process, was dumped to the bottom of Tank 8D-1. Approximately 90% of the spent zeolite was transferred from Tank 8D-1 into Tank 8D-2 by the start of vitrification processing in June 1996. Periodically, the remaining spent zeolite contained in Tank 8D-1 is incrementally transferred to 8D-2. The combined waste in Tank 8D-2 continues to be processed through the Vitrification Facility into canisters for final repository disposal.

  5. Energy Efficiency of D2D Multi-User Cooperation.

    PubMed

    Zhang, Zufan; Wang, Lu; Zhang, Jie

    2017-03-28

    The Device-to-Device (D2D) communication system is an important part of heterogeneous networks. It has great potential to improve spectrum efficiency, throughput and energy efficiency cooperation of multiple D2D users with the advantage of direct communication. When cooperating, D2D users expend extraordinary energy to relay data to other D2D users. Hence, the remaining energy of D2D users determines the life of the system. This paper proposes a cooperation scheme for multiple D2D users who reuse the orthogonal spectrum and are interested in the same data by aiming to solve the energy problem of D2D users. Considering both energy availability and the Signal to Noise Ratio (SNR) of each D2D user, the Kuhn-Munkres algorithm is introduced in the cooperation scheme to solve relay selection problems. Thus, the cooperation issue is transformed into a maximum weighted matching (MWM) problem. In order to enhance energy efficiency without the deterioration of Quality of Service (QoS), the link outage probability is derived according to the Shannon Equation by considering the data rate and delay. The simulation studies the relationships among the number of cooperative users, the length of shared data, the number of data packets and energy efficiency.

  6. Learning Curve for D2 Lymphadenectomy in Gastric Cancer

    PubMed Central

    Rebasa, Pere; Montmany, Sandra; Navarro, Salvador

    2013-01-01

    Background. D2 lymphadenectomy is a demanding technique which is associated with high morbidity in the West. We report our experience with D2 lymphadenectomy after a training period in Japan. Methods. Prospective, descriptive study in 133 consecutive patients undergoing radical gastrectomy for gastric adenocarcinoma from 2005 to 2011. We analysed the number of lymph nodes removed, observed morbidity/mortality compared with the predictions of POSSUM and O-POSSUM, survival, and disease-free interval for patients with D1 and D2 lymphadenectomy. Results. The morbidity rate in patients with D1 lymphadenectomy was 59.4%. For D2 it was 47.7%. The mortality rate in patients with D1 was 6.7%. In the D2 group it was 6.8%. Median survival was 42.9 months in D1 and 55 months in D2. The disease-free interval was 49 months for D1 and 58 months for D2. Conclusion. The learning curve for D2 lymphadenectomy presents acceptable rates of morbidity and mortality, providing that the technique is learnt at a center with extensive experience. PMID:23844296

  7. D2-40/podoplanin expression in the human placenta.

    PubMed

    Wang, Y; Sun, J; Gu, Y; Zhao, S; Groome, L J; Alexander, J S

    2011-01-01

    Placental tissue expresses many lymphatic markers. The current study was undertaken to examine if D2-40/podoplanin, a lymphatic endothelial marker, was expressed in the human placenta, and how it is altered developmentally and pathologically. We examined D2-40/podoplanin and VEGFR-3 expressions in placentas from normotensive pregnancies at different gestational ages and in placentas from women with clinically defined preeclampsia. D2-40 expression in systemic lymphatic vessel endothelium served as a positive control. Protein expression for D2-40, VEGFR-3, and β-actin was determined by Western blot in placentas from normotensive (n = 6) and preeclamptic (n = 5) pregnancies. Our results show that D2-40/podoplanin was strongly expressed in the placenta, mainly as a network plexus pattern in the villous stroma throughout gestation. CD31 was limited to villous core fetal vessel endothelium and VEGFR-3 was found in both villous core fetal vessel endothelium and trophoblasts. D2-40/podoplanin expression was significantly decreased, and VEGFR-3 significantly increased in preeclamptic placental tissues compared to normotensive placental controls. Placental villous stroma is a reticular-like structure, and the localization of D2-40 to the stroma suggests that a lymphatic-like conductive network may exist in the human placenta. D2-40/podoplanin is an O-linked sialoglycoprotein. Although little is known regarding biological functions of sialylated glycoproteins within the placenta, placental D2-40/podoplanin may support fetal vessel angiogenesis during placenta development and reduced D2-40/podoplanin expression in preeclamptic placenta may contribute to altered interstitial fluid homeostasis and impaired angiogenesis in this pregnancy disorder.

  8. An investigation of nonadiabatic interactions in Cl(2Pj) + D2 via crossed-molecular-beam scattering.

    PubMed

    Parsons, Bradley F; Chandler, David W

    2005-05-01

    We have determined limits on the cross section for both electronically nonadiabatic excitation and quenching in the Cl((2)P(j)) + D(2) system. Our experiment incorporates crossed-molecular-beam scattering with state-selective Cl((2)P(12,32)) detection and velocity-mapped ion imaging. By colliding atomic chlorine with D(2), we address the propensity for collisions that result in a change of the spin-orbit level of atomic chlorine either through electronically nonadiabatic spin-orbit excitation Cl((2)P(32)) + D(2)-->Cl(*)((2)P(12)) + D(2) or through electronically nonadiabatic spin-orbit quenching Cl(*)((2)P(12)) + D(2)-->Cl((2)P(32)) + D(2). In the first part of this report, we estimate an upper limit for the electronically nonadiabatic spin-orbit excitation cross section at a collision energy of 5.3 kcal/mol, which lies above the energy of the reaction barrier (4.9 kcal/mol). Our analysis and simulation of the experimental data determine an upper limit for the excitation cross section as sigma(NA)< or =0.012 A(2). In the second part of this paper we investigate the propensity for electronically nonadiabatic spin-orbit quenching of Cl(*) following a collision with D(2) or He. We perform these experiments at collision energies above and below the energy of the reaction barrier. By comparing the amount of scattered Cl(*) in our images to the amount of Cl(*) lost from the atomic beam we obtain the maximum cross section for electronically nonadiabatic quenching as sigma(NA)< or =15(-15) (+44) A(2) for a collision energy of 7.6 kcal/mol. Our experiments show the probability for electronically nonadiabatic quenching in Cl(*) + D(2) to be indistinguishable to that for the kinematically identical system of Cl(*) + He.

  9. [D-2-hydroxyglutaric aciduria. Report of two cases].

    PubMed

    Mahfoud, Antionieta; Domínguez, Carmen Luisa; Rashed, Mohamed; Durán, Marinus; Rodríguez, Tania; Rodríguez, Daniel; Landa, Vanesa

    2009-09-01

    D-2-hydroxyglutaric aciduria (D-2-HGA) is a cerebral organic aciduria characterized by the accumulation of abnormal amounts of D-2-hydroxyglutaric acid in cerebrospinal fluid, blood, and urine. The clinical phenotype varies widely from neonatal severe epileptic encephalopathy to asymptomatic. Magnetic resonance imaging of affected patients typically show signs of delayed cerebral maturation, ventricular abnormalities and the presence of sub-ependymal cysts in the first months of life. We present clinical, biochemical and brain magnetic resonance imaging data of two pediatric patients with D-2-hydroxyglutaric aciduria. One patient presented with severe early infantile-onset epileptic encephalopathy, marked hypotonia, visual deficit, developmental delay and abnormal neuroradiological findings; while the other had hypotonia and development delay. Our findings reinforce the described phenotype of this rare neurometabolic inherited disorder. The diagnostic approach is based on clinical findings and the neuroimaging pattern and is established by the detection of D-2-hydroxyglutaric acid in body fluids. We suggest considering D-2-hydroxyglutaric aciduria in the differential diagnosis of any neonate or infant with epileptic encephalopathy and CNS dysfunction of unknown origin.

  10. Photoaffinity ligand for dopamine D2 receptors: azidoclebopride

    SciTech Connect

    Niznik, H.B.; Guan, J.H.; Neumeyer, J.L.; Seeman, P.

    1985-02-01

    In order to label D2 dopamine receptors selectively and covalently by means of a photosensitive compound, azidoclebopride was synthesized directly from clebopride. The dissociation constant (KD) of clebopride for the D2 dopamine receptor (canine brain striatum) was 1.5 nM, while that for azidoclebopride was 21 nM. The affinities of both clebopride and azidoclebopride were markedly reduced in the absence of sodium chloride. In the presence of ultraviolet light, azidoclebopride inactivated D2 dopamine receptors irreversibly, as indicated by the inability of the receptors to bind (/sup 3/H)spiperone. Maximal photoinactivation of about 60% of the D2 dopamine receptors occurred at 1 microM azidoclebopride; 30% of the receptors were inactivated at 80 nM azidoclebopride (pseudo-IC50). Dopamine agonists selectively protected the D2 receptors from being inactivated by azidoclebopride, the order of potency being (-)-N-n-propylnorapomorphine greater than apomorphine greater than (+/-)-6,7-dihydroxy-2-aminotetralin greater than (+)-N-n-propylnorapomorphine greater than dopamine greater than noradrenaline greater than serotonin. Similarly, dopaminergic antagonists prevented the photoinactivation of D2 receptors by azidoclebopride with the following order of potency: spiperone greater than (+)-butaclamol greater than haloperidol greater than clebopride greater than (-)-sulpiride greater than (-)-butaclamol.

  11. Role of Dopamine D2 Receptors in Human Reinforcement Learning

    PubMed Central

    Eisenegger, Christoph; Naef, Michael; Linssen, Anke; Clark, Luke; Gandamaneni, Praveen K; Müller, Ulrich; Robbins, Trevor W

    2014-01-01

    Influential neurocomputational models emphasize dopamine (DA) as an electrophysiological and neurochemical correlate of reinforcement learning. However, evidence of a specific causal role of DA receptors in learning has been less forthcoming, especially in humans. Here we combine, in a between-subjects design, administration of a high dose of the selective DA D2/3-receptor antagonist sulpiride with genetic analysis of the DA D2 receptor in a behavioral study of reinforcement learning in a sample of 78 healthy male volunteers. In contrast to predictions of prevailing models emphasizing DA's pivotal role in learning via prediction errors, we found that sulpiride did not disrupt learning, but rather induced profound impairments in choice performance. The disruption was selective for stimuli indicating reward, whereas loss avoidance performance was unaffected. Effects were driven by volunteers with higher serum levels of the drug, and in those with genetically determined lower density of striatal DA D2 receptors. This is the clearest demonstration to date for a causal modulatory role of the DA D2 receptor in choice performance that might be distinct from learning. Our findings challenge current reward prediction error models of reinforcement learning, and suggest that classical animal models emphasizing a role of postsynaptic DA D2 receptors in motivational aspects of reinforcement learning may apply to humans as well. PMID:24713613

  12. Role of dopamine D2 receptors in human reinforcement learning.

    PubMed

    Eisenegger, Christoph; Naef, Michael; Linssen, Anke; Clark, Luke; Gandamaneni, Praveen K; Müller, Ulrich; Robbins, Trevor W

    2014-09-01

    Influential neurocomputational models emphasize dopamine (DA) as an electrophysiological and neurochemical correlate of reinforcement learning. However, evidence of a specific causal role of DA receptors in learning has been less forthcoming, especially in humans. Here we combine, in a between-subjects design, administration of a high dose of the selective DA D2/3-receptor antagonist sulpiride with genetic analysis of the DA D2 receptor in a behavioral study of reinforcement learning in a sample of 78 healthy male volunteers. In contrast to predictions of prevailing models emphasizing DA's pivotal role in learning via prediction errors, we found that sulpiride did not disrupt learning, but rather induced profound impairments in choice performance. The disruption was selective for stimuli indicating reward, whereas loss avoidance performance was unaffected. Effects were driven by volunteers with higher serum levels of the drug, and in those with genetically determined lower density of striatal DA D2 receptors. This is the clearest demonstration to date for a causal modulatory role of the DA D2 receptor in choice performance that might be distinct from learning. Our findings challenge current reward prediction error models of reinforcement learning, and suggest that classical animal models emphasizing a role of postsynaptic DA D2 receptors in motivational aspects of reinforcement learning may apply to humans as well.

  13. Quantum dynamics of the D2+OH reaction

    NASA Astrophysics Data System (ADS)

    Zhang, Dong H.; Yang, Minghui; Lee, Soo-Y.

    2002-02-01

    This paper presents fully converged integral cross sections for the D2(j1=0,2,4)+OH(j2=0,2,4)→HOD+D reaction on the YZCL2 potential energy surface. It is found that the influence of reagent rotation excitation on reactivity is relatively mild compared with that of the D2 vibration excitation, but is fairly important to the thermal rate constant at low temperature. In general, the OH rotation excitation tends to hinder the reaction, and the D2 rotation excitation tends to enhance the reactivity. The simultaneous reagent rotation has some correlated effect, with the influence of the D2 rotation excitation considerably dependent on the OH rotation excitation. It is also found that the reaction is strongly dependent on j12 (the coupled angular momentum between j1 and j2), K0 (the projection of the reagent rotation on the body fixed axis), and the parity of the system, in particular for either the OH or D2 rotationally excited initial states, but this dependence becomes relatively weaker as the collision energy increases. Excellent agreement achieved between theory and experiment on the thermal rate coefficients for temperatures up to 400 K clearly shows that the YZCL2 potential energy surface is capable of producing "quantitatively" accurate results for the title reaction.

  14. D2-D1 phase transition of columnar liquid crystals

    NASA Astrophysics Data System (ADS)

    Sun, Y. F.; Swift, J.

    1986-04-01

    The D2-D1 phase transition in columnar liquid crystals of the HAT series [e.g., HAT11 (triphenelene hexa-n-dodecanoate)] is discussed within the framework of Landau theory. The order parameters which describe the transition are abstracted from a tensor density function, and are associated with two irreducible representations of the symmetry group of the high-temperature D2 phase. A mechanism for a first-order transition is then suggested in accordance with both theoretical considerations and the experimental result for the D2-D1 transition. Two possible arrangements of the herringbone structure of the D1 phase are obtained, each of which gives six orientational states in the low-temperature D1 phase.

  15. L(d,2,1)-labeling of sun graphs

    NASA Astrophysics Data System (ADS)

    Indriati, Diari; Martini, Titin S.; Herlinawati, Novita

    2014-03-01

    For positive integer d, L(d,2,1)-labeling of a graph G is a function f from V(G) to the positive integers, f:V(G)→{1,2,...} such that |f(u)-f(v)|≥d if the distance between any 2 vertices u and v is 1 (D(u,v) = 1), |f(u)-f(v)|≥2 if D(u,v) = 2, and |f(u)-f(v)|≥1 if D(u,v) = 3. The L(d,2,1)-labeling number kd(G) of a graph G is the smallest positive integer kd such that G has an L(d,2,1)-labeling with kd as the maximum label. This paper presents a general kd-value of sun graphs Sn for any d ≥ 3 and n ≥ 3.

  16. Molecular dynamics simulations of D2O ice photodesorption

    NASA Astrophysics Data System (ADS)

    Arasa, C.; Andersson, S.; Cuppen, H.; van Dishoeck, E. F.; Kroes, G. J.

    2011-05-01

    We present results of MD calculations performed to study the photodissociation of D2O in an amorphous ice at different ice temperatures in order to investigate isotope effects on the photodesorption processes. In dense interstellar clouds, small dust particles of micrometer silicates are covered by ice mantles, mainly consisting of H2O and also of CO, CO2. Previous MD calculations of H2O ice at Tice=10-90 K show that the photodesorption of H while OH remains trapped is the main outcome in the first three monolayers (MLs). On the other hand, the H and OH photofragments released recombine or are trapped at separate positions in the deeper MLs and can react with other species in the ice. Desorption and trapping probabilities have been calculated following photoexcitation of D2O amorphous ice at 10, 20, 60 and 90 K, and the main conclusions agree with previous calculations of H2O ice. But, the average D photodesorption probability is smaller than that of the H atom, whereas the average OD radical photodesorption probability is larger than that of OH, and the average D2O photodesorption probability is larger than that for H2O due to the D2O kick-out mechanism. The total (OD + D2O) yield has been compared with experiments and the total (OH + H2O) yield from previous simulations. We find better agreement when we compare experimental yields with calculated yields for D2O ice than when we compare with calculated yields for H2O ice.

  17. Terahertz absorption spectrum of D 2O vapor

    NASA Astrophysics Data System (ADS)

    Yu, B. L.; Yang, Y.; Zeng, F.; Xin, X.; Alfano, R. R.

    2006-02-01

    The absorption spectrum of D2O vapor from 0.2 to 2.0 THz (6.7-67 cm-1) which is associated with rotational modes was measured at one atmosphere using terahertz time-domain spectroscopy (THz-TDS). The linewidth and collisional dephasing times were measured for 26 pure rotational transitions in the ground vibrational state (0 0 0). The temperature dependence of the linewidth (Δν) behaves as Δν ∼ T-3/4 and the linewidth decrease with increasing temperature is attributed to the 1/r6 force of interaction between colliding D2O molecules.

  18. Novel Bivalent Ligands for D2/D3 Dopamine Receptors: Significant Cooperative Gain in D2 Affinity and Potency

    PubMed Central

    2012-01-01

    This report describes development of a series of novel bivalent molecules with a pharmacophore derived from the D2/D3 agonist 5-OH-DPAT. The spacer length in the bivalent compounds had a pronounced influence on affinity for D2 receptors. A 23-fold increase of D2 affinity was observed at a spacer length of 9 or 10 (compounds 11d and 14b) as compared to monovalent 5-OH-DPAT (Ki; 2.5 and 2.0 vs 59 nM for 11d and 14b vs 5-OH-DPAT, respectively). The functional potency of 11d and 14b indicated a 24- and 94-fold increase in potency at the D2 receptor as compared to 5-OH-DPAT (EC50; 1.7 and 0.44 vs 41 nM for 11d and 14b vs 5-OH-DPAT, respectively). These are the most potent bivalent agonists for the D2 receptor known to date. This synergism is consonant with cooperative interaction at the two orthosteric binding sites in the homodimeric receptor. PMID:23275802

  19. 3-Chlorotyramine Acting as Ligand of the D2 Dopamine Receptor. Molecular Modeling, Synthesis and D2 Receptor Affinity.

    PubMed

    Angelina, Emilio; Andujar, Sebastian; Moreno, Laura; Garibotto, Francisco; Párraga, Javier; Peruchena, Nelida; Cabedo, Nuria; Villecco, Margarita; Cortes, Diego; Enriz, Ricardo D

    2015-01-01

    We synthesized and tested 3-chlorotyramine as a ligand of the D2 dopamine receptor. This compound displayed a similar affinity by this receptor to that previously reported for dopamine. In order to understand further the experimental results we performed a molecular modeling study of 3-chlorotyramine and structurally related compounds. By combining molecular dynamics simulations with semiempirical (PM6), ab initio and density functional theory calculations, a simple and generally applicable procedure to evaluate the binding energies of these ligands interacting with the D2 dopamine receptors is reported here. These results provided a clear picture of the binding interactions of these compounds from both structural and energetic view points. A reduced model for the binding pocket was used. This approach allowed us to perform more accurate quantum mechanical calculations as well as to obtain a detailed electronic analysis using the Quantum Theory of Atoms in Molecules (QTAIM) technique. Molecular aspects of the binding interactions between ligands and the D2 dopamine receptor are discussed in detail. A good correlation between the relative binding energies obtained from theoretical calculations and experimental IC50 values was obtained. These results allowed us to predict that 3-chlorotyramine possesses a significant affinity by the D2 -DR. Our theoretical predictions were experimentally corroborated when we synthesized and tested 3-chlorotyramine which displayed a similar affinity by the D2 -DR to that reported for DA.

  20. Antagonism of the prostaglandin D2 receptor 1 suppresses nicotinic acid-induced vasodilation in mice and humans.

    PubMed

    Cheng, Kang; Wu, Tsuei-Ju; Wu, Kenneth K; Sturino, Claudio; Metters, Kathleen; Gottesdiener, Keith; Wright, Samuel D; Wang, Zhaoyin; O'Neill, Gary; Lai, Eseng; Waters, M Gerard

    2006-04-25

    Nicotinic acid (NA) is commonly used to treat dyslipidemia, but it elicits an adverse effect, termed flushing, which consists of cutaneous vasodilation with associated discomfort. An animal model of NA-induced flushing has been established in mice. As in humans, NA stimulated vasodilation in a dose-dependent manner, was associated with an increase of the vasodilatory prostaglandin (PG) D2 in plasma and could be blocked by pretreatment with aspirin. Two PGD2 receptors have been identified: PGD2 receptor 1 (DP1, also called DP) and PGD2 receptor 2 (DP2, sometimes termed CRTH2). DP2 does not mediate NA-induced vasodilation; the DP2-specific agonist DK-PGD2 (13,14-dihydro-15-keto-PGD2) did not induce cutaneous vasodilation, and DP2-/- mice had a normal vasodilatory response to NA. By contrast, BW245C, a DP1-selective agonist, induced vasodilation in mice, and MK-0524, a DP1-selective antagonist, blocked both PGD2- and NA-induced vasodilation. NA-induced vasodilation was also studied in DP1+/+, DP1+/-, and DP1-/- mice; although NA-induced vasodilation depended almost completely on DP1 in female mice, it depended only partially on DP1 in male mice. The residual NA-induced vasodilation in male DP-/- mice was aspirin-sensitive. Thus, in the mouse, DP1 appears to be an important component involved in NA-induced vasodilation, but other cyclooxygenase-dependent mechanisms also may be involved. A clinical study in healthy men and women demonstrated that treatment with MK-0524 reduced the symptoms of flushing and the increase in skin perfusion after the administration of NA. These studies suggest that DP1 receptor antagonism may be an effective means to suppress NA-induced flushing in humans.

  1. Mammal-like striatal functions in Anolis. II. Distribution of dopamine D(1) and D(2) receptors, and a laminar pattern of basal ganglia sub-systems.

    PubMed

    Clark, E C; Baxter, L R; Dure, L S; Ackermann, R F; Kemp, G F; Bachus, S E

    2000-11-01

    We used in situ autoradiographic ligand binding methods to determine the occurrence and distribution of dopamine D(1) and D(2) receptor sub-types in the anole lizard, Anolis carolinensis. Both were present and exhibited pharmacological specificity characteristics similar to those described for mammals. However, unlike in mammals where in the neostriatum [outside the nucleus accumbens/olfactory tubercle complex (NA/OT)] these receptors exhibit only slight dorsolateral (D(2) high, D(1) low) to ventromedial (D(1 )high, D(2) low) gradients that co mingle extensively, in the anole striatum outside the NA/OT there was a striking laminar pattern, with little if any overlap between D(2) (high in a dorsal band) and D(1) (high ventral to the D(2) band) distributions. As D(1) receptors are related to the direct and D(2) to the indirect basal ganglia (BG) subsystems in mammals, we also determined anole striatal distributions of pre-proenkephalin mRNA, a marker for striatal efferents to the indirect BG subsystem in mammals. Here, too, there was a striking laminar pattern, with pre-proenkephalin mRNA in a band similar to that seen for D(2) receptors. The crisp neuroanatomical separation between these classic BG subsystem markers in Anolis striatum make this species attractive for the study of such systems' functions during behavior.

  2. Frontal D2/3 Receptor Availability in Schizophrenia Patients Before and After Their First Antipsychotic Treatment: Relation to Cognitive Functions and Psychopathology

    PubMed Central

    Nørbak-Emig, Henrik; Ebdrup, Bjørn H.; Fagerlund, Birgitte; Svarer, Claus; Rasmussen, Hans; Friberg, Lars; Allerup, Peter N.; Rostrup, Egill; Pinborg, Lars H.

    2016-01-01

    Background: We have previously reported associations between frontal D2/3 receptor binding potential positive symptoms and cognitive deficits in antipsychotic-naïve schizophrenia patients. Here, we examined the effect of dopamine D2/3 receptor blockade on cognition. Additionally, we explored the relation between frontal D2/3 receptor availability and treatment effect on positive symptoms. Methods: Twenty-five antipsychotic-naïve first-episode schizophrenia patients were examined with the Positive and Negative Syndrome Scale, tested with the cognitive test battery Cambridge Neuropsychological Test Automated Battery, scanned with single-photon emission computerized tomography using the dopamine D2/3 receptor ligand [123I]epidepride, and scanned with MRI. After 3 months of treatment with either risperidone (n=13) or zuclopenthixol (n=9), 22 patients were reexamined. Results: Blockade of extrastriatal dopamine D2/3 receptors was correlated with decreased attentional focus (r = -0.615, P=.003) and planning time (r = -0.436, P=.048). Moreover, baseline frontal dopamine D2/3 binding potential and positive symptom reduction correlated positively (D2/3 receptor binding potential left frontal cortex rho = 0.56, P=.003; D2/3 receptor binding potential right frontal cortex rho = 0.48, P=.016). Conclusions: Our data support the hypothesis of a negative influence of D2/3 receptor blockade on specific cognitive functions in schizophrenia. This is highly clinically relevant given the well-established association between severity of cognitive disturbances and a poor functional outcome in schizophrenia. Additionally, the findings support associations between frontal D2/3 receptor binding potential at baseline and the effect of antipsychotic treatment on positive symptoms. PMID:26819282

  3. Repeated Cocaine Exposure Decreases Dopamine D2-Like Receptor Modulation of Ca2+ Homeostasis in Rat Nucleus Accumbens Neurons

    PubMed Central

    PEREZ, MARIELA F.; FORD, KERSTIN A.; GOUSSAKOV, IVAN; STUTZMANN, GRACE E.; HU, XIU-TI

    2013-01-01

    The nucleus accumbens (NAc) is a limbic structure in the forebrain that plays a critical role in cognitive function and addiction. Dopamine modulates activity of medium spiny neurons (MSNs) in the NAc. Both dopamine D1-like and D2-like receptors (including D1R or D1,5R and D2R or D2,3,4R, respectively) are thought to play critical roles in cocaine addiction. Our previous studies demonstrated that repeated cocaine exposure (which alters dopamine transmission) decreases excitability of NAc MSNs in cocaine-sensitized, withdrawn rats. This decrease is characterized by a reduction in voltage-sensitive Na+ currents and high voltage-activated Ca2+ currents, along with increased voltage-gated K+ currents. These changes are associated with enhanced activity in the D1R/cAMP/PKA/protein phosphatase 1 pathway and diminished calcineurin function. Although D1R-mediated signaling is enhanced by repeated cocaine exposure, little is known whether and how the D2R is implicated in the cocaine-induced NAc dysfunction. Here, we performed a combined electrophysiological, biochemical, and neuroimaging study that reveals the cocaine-induced dysregulation of Ca2+ homeostasis with involvement of D2R. Our novel findings reveal that D2R stimulation reduced Ca2+ influx preferentially via the L-type Ca2+ channels and evoked intracellular Ca2+ release, likely via inhibiting the cAMP/PKA cascade, in the NAc MSNs of drug-free rats. However, repeated cocaine exposure abolished the D2R effects on modulating Ca2+ homeostasis with enhanced PKA activity and led to a decrease in whole-cell Ca2+ influx. These adaptations, which persisted for 21 days during cocaine abstinence, may contribute to the mechanism of cocaine withdrawal. PMID:20665696

  4. An alternative pathway of vitamin D2 metabolism Cytochrome P450scc (CYP11A1)-mediated conversion to 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2

    PubMed Central

    Slominski, Andrzej; Semak, Igor; Wortsman, Jacobo; Zjawiony, Jordan; Li, Wei; Zbytek, Blazej; Tuckey, Robert C.

    2007-01-01

    We report an alternative, hydroxylating pathway for the metabolism of vitamin D2 in a cytochrome P450 side chain cleavage (P450scc; CYP11A1) reconstituted system. NMR analyses identified solely 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2 derivatives. 20-Hydroxyvitamin D2 was produced at a rate of 0.34 mol·min−1·mol−1 P450scc, and 17,20-dihydroxyvitamin D2 was produced at a rate of 0.13 mol·min−1·mol−1. In adrenal mitochondria, vitamin D2 was metabolized to six monohydroxy products. Nevertheless, aminoglutethimide (a P450scc inhibitor) inhibited this adrenal metabolite formation. Initial testing of metabolites for biological activity showed that, similar to vitamin D2, 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2 inhibited DNA synthesis in human epidermal HaCaT keratinocytes, although to a greater degree. 17,20-Dihydroxyvitamin D2 stimulated transcriptional activity of the involucrin promoter, again to a significantly greater extent than vitamin D2, while the effect of 20-hydroxyvitamin D2 was statistically insignificant. Thus, P450scc can metabolize vitamin D2 to generate novel products, with intrinsic biological activity (at least in keratinocytes). PMID:16817851

  5. Reconstruction-based 3D/2D image registration.

    PubMed

    Tomazevic, Dejan; Likar, Bostjan; Pernus, Franjo

    2005-01-01

    In this paper we present a novel 3D/2D registration method, where first, a 3D image is reconstructed from a few 2D X-ray images and next, the preoperative 3D image is brought into the best possible spatial correspondence with the reconstructed image by optimizing a similarity measure. Because the quality of the reconstructed image is generally low, we introduce a novel asymmetric mutual information similarity measure, which is able to cope with low image quality as well as with different imaging modalities. The novel 3D/2D registration method has been evaluated using standardized evaluation methodology and publicly available 3D CT, 3DRX, and MR and 2D X-ray images of two spine phantoms, for which gold standard registrations were known. In terms of robustness, reliability and capture range the proposed method outperformed the gradient-based method and the method based on digitally reconstructed radiographs (DRRs).

  6. D2 dopamine receptor regulation of learning, sleep and plasticity.

    PubMed

    França, A S C; Lobão-Soares, B; Muratori, L; Nascimento, G; Winne, J; Pereira, C M; Jeronimo, S M B; Ribeiro, S

    2015-04-01

    Dopamine and sleep have been independently linked with hippocampus-dependent learning. Since D2 dopaminergic transmission is required for the occurrence of rapid-eye-movement (REM) sleep, it is possible that dopamine affects learning by way of changes in post-acquisition REM sleep. To investigate this hypothesis, we first assessed whether D2 dopaminergic modulation in mice affects novel object preference, a hippocampus-dependent task. Animals trained in the dark period, when sleep is reduced, did not improve significantly in performance when tested 24h after training. In contrast, animals trained in the sleep-rich light period showed significant learning after 24h. When injected with the D2 inverse agonist haloperidol immediately after the exploration of novel objects, animals trained in the light period showed reduced novelty preference upon retesting 24h later. Next we investigated whether haloperidol affected the protein levels of plasticity factors shown to be up-regulated in an experience-dependent manner during REM sleep. Haloperidol decreased post-exploration hippocampal protein levels at 3h, 6h and 12h for phosphorylated Ca(2+)/calmodulin-dependent protein kinase II, at 6h for Zif-268; and at 12h for the brain-derived neurotrophic factor. Electrophysiological and kinematic recordings showed a significant decrease in the amount of REM sleep following haloperidol injection, while slow-wave sleep remained unaltered. Importantly, REM sleep decrease across animals was strongly correlated with deficits in novelty preference (Rho=0.56, p=0.012). Altogether, the results suggest that the dopaminergic regulation of REM sleep affects learning by modulating post-training levels of calcium-dependent plasticity factors.

  7. Coupling of D2R Short but not D2R Long receptor isoform to the Rho/ROCK signaling pathway renders striatal neurons vulnerable to mutant huntingtin.

    PubMed

    Galan-Rodriguez, Beatriz; Martin, Elodie; Brouillet, Emmanuel; Déglon, Nicole; Betuing, Sandrine; Caboche, Jocelyne

    2017-01-01

    Huntington's disease, an inherited neurodegenerative disorder, results from abnormal polyglutamine extension in the N-terminal region of the huntingtin protein. This mutation causes preferential degeneration of striatal projection neurons. We previously demonstrated, in vitro, that dopaminergic D2 receptor stimulation acted in synergy with expanded huntingtin to increase aggregates formation and striatal death through activation of the Rho/ROCK signaling pathway. In vivo, in a lentiviral-mediated model of expanded huntingtin expression in the rat striatum, we found that the D2 antagonist haloperidol protects striatal neurons against expanded huntingtin-mediated toxicity. Two variant transcripts are generated by alternative splicing of the of D2 receptor gene, the D2R-Long and the D2R-Short, which are thought to play different functional roles. We show herein that overexpression of D2R-Short, but not D2R-Long in cell lines is associated with activation of the RhoA/ROCK signaling pathway. In striatal neurons in culture, the selective D2 agonist Quinpirole triggers phosphorylation of cofilin, a downstream effector of ROCK, which is abrogated by siRNAs that knockdown both D2R-Long and D2R-Short, but not by siRNAs targeting D2R-Long alone. Aggregate formation and neuronal death induced by expanded huntingtin, were potentiated by Quinpirole. This D2 agonist-mediated effect was selectively inhibited by the siRNA targeting both D2R-Long and D2R-Short but not D2R-Long alone. Our data provide evidence for a specific coupling of D2R-Short to the RhoA/ROCK/cofilin pathway, and its involvement in striatal vulnerability to expanded huntingtin. A new route for targeting Rho-ROCK signaling in Huntington's disease is unraveled with our findings.

  8. Generating generalized G{sub D-2} solutions

    SciTech Connect

    Breton, N.; Lopez, L. A.; Feinstein, A.

    2008-06-15

    We show how one can systematically construct vacuum solutions to Einstein field equations with D-2 commuting Killing vectors in D>4 dimensions. The construction uses Einstein-scalar field seed solutions in four dimensions and is performed both for the case when all the Killing directions are spacelike, as well as when one of the Killing vectors is timelike. The later case corresponds to generalizations of stationary axially symmetric solutions to higher dimensions. Some examples representing generalizations of known higher dimensional stationary solutions are discussed in terms of their rod structure and horizon locations and deformations.

  9. In vivo mesolimbic D2/3 receptor binding predicts posttherapeutic clinical responses in restless legs syndrome: a positron emission tomography study.

    PubMed

    Oboshi, Yumi; Ouchi, Yasuomi; Yagi, Shunsuke; Kono, Satoshi; Nakai, Noriyoshi; Yoshikawa, Etsuji; Futatsubashi, Masami; Terada, Tatsuhiro; Kim, Kang; Harada, Kiyoshi

    2012-04-01

    Although D2/3 agonists have been used as a first-line medication for idiopathic restless legs syndrome (iRLS), findings on D2/3 receptors have been inconsistent. Here, we aimed to clarify the contribution of D2/3 receptor function to the clinical symptoms of iRLS by comparing the binding potential (BP(ND)) of [(11)C]raclopride with clinical improvements after D2/3 stimulation by pramipexole. Eight drug-naïve, iRLS patients and eight age-matched healthy subjects were scanned with positron emission tomography (PET). After PET scans, all patients received pramipexole (0.125 mg) orally for 2 weeks. Patients were evaluated every day with several standardized clinical tests. The BP(ND) values were compared using regions of interest and voxel-based methods. Results showed that the mean magnitude of [(11)C]raclopride BP(ND) in the mesolimbic dopamine region (nucleus accumbens (NA) and caudate) was significantly lower in the iRLS group. No significant differences between groups were observed in the putamen. The NA [(11)C]raclopride BP(ND) levels correlated negatively with clinical severity scores and positively with the degree of posttreatment improvement in iRLS. The present results suggest that alterations in mesolimbic D2/3 receptor function reflect the pathophysiology of iRLS, and the baseline availability of D2/3 receptors may predict the clinical outcome after D2/3 agonist treatment.

  10. Chiral Potts spin glass in d=2 and 3 dimensions.

    PubMed

    Çağlar, Tolga; Berker, A Nihat

    2016-09-01

    The chiral spin-glass Potts system with q=3 states is studied in d=2 and 3 spatial dimensions by renormalization-group theory and the global phase diagrams are calculated in temperature, chirality concentration p, and chirality-breaking concentration c, with determination of phase chaos and phase-boundary chaos. In d=3, the system has ferromagnetic, left-chiral, right-chiral, chiral spin-glass, and disordered phases. The phase boundaries to the ferromagnetic, left- and right-chiral phases show, differently, an unusual, fibrous patchwork (microreentrances) of all four (ferromagnetic, left-chiral, right-chiral, chiral spin-glass) ordered phases, especially in the multicritical region. The chaotic behavior of the interactions, under scale change, are determined in the chiral spin-glass phase and on the boundary between the chiral spin-glass and disordered phases, showing Lyapunov exponents in magnitudes reversed from the usual ferromagnetic-antiferromagnetic spin-glass systems. At low temperatures, the boundaries of the left- and right-chiral phases become thresholded in p and c. In d=2, the chiral spin-glass Potts system does not have a spin-glass phase, consistently with the lower-critical dimension of ferromagnetic-antiferromagnetic spin glasses. The left- and right-chirally ordered phases show reentrance in chirality concentration p.

  11. Marginal fluctuations as instantons on M2/D2-branes

    NASA Astrophysics Data System (ADS)

    Naghdi, M.

    2014-03-01

    We introduce some (anti-) M/D-branes through turning on the corresponding field strengths of the 11- and 10-dimensional supergravity theories over spaces, where we use and for the internal spaces. Indeed, when we add M2/D2-branes on the same directions with the near horizon branes of the Aharony-Bergman-Jafferis-Maldacena model, all symmetries and supersymmetries are preserved trivially. In this case, we obtain a localized object just in the horizon. This normalizable bulk massless scalar mode is a singlet of and , and it agrees with a marginal boundary operator of the conformal dimension of . However, after performing a special conformal transformation, we see that the solution is localized in the Euclideanized space and is attributable to the included anti-M2/D2-branes, which are also necessary to ensure that there is no back-reaction. The resultant theory now breaks all supersymmetries to , while the other symmetries are so preserved. The dual boundary operator is then set up from the skew-whiffing of the representations and for the supercharges and scalars, respectively, while the fermions remain fixed in of the original theory. Besides, we also address another alternate bulk to boundary matching procedure through turning on one of the gauge fields of the full gauge group along the same lines with a similar situation to the one faced in the AdS/CFT correspondence. The latter approach covers the difficulty already faced with in the bulk-boundary matching procedure for as well.

  12. 16 CFR Appendix D2 to Part 305 - Water Heaters-Electric

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 1 2014-01-01 2014-01-01 false Water Heaters-Electric D2 Appendix D2 to Part 305 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS... LABELING RULEâ) Pt. 305, App. D2 Appendix D2 to Part 305—Water Heaters—Electric Range Information...

  13. Increased consumption of ethanol and sugar water in mice lacking the dopamine D2 long receptor.

    PubMed

    Bulwa, Zachary B; Sharlin, Jordan A; Clark, Peter J; Bhattacharya, Tushar K; Kilby, Chessa N; Wang, Yanyan; Rhodes, Justin S

    2011-11-01

    Individual differences in dopamine D2 receptor (D2R) expression in the brain are thought to influence motivation and reinforcement for ethanol and other rewards. D2R exists in two isoforms, D2 long (D2LR) and D2 short (D2SR), produced by alternative splicing of the same gene. The relative contributions of D2LR versus D2SR to ethanol and sugar water drinking are not known. Genetic engineering was used to produce a line of knockout (KO) mice that lack D2LR and consequently have increased expression of D2SR. KO and wild-type (WT) mice of both sexes were tested for intake of 20% ethanol, 10% sugar water and plain tap water using established drinking-in-the-dark procedures. Mice were also tested for effects of the D2 antagonist eticlopride on intake of ethanol to determine whether KO responses were caused by lack of D2LR or overrepresentation of D2SR. Locomotor activity on running wheels and in cages without wheels was also measured for comparison. D2L KO mice drank significantly more ethanol than WT in both sexes. KO mice drank more sugar water than WT in females but not in males. Eticlopride dose dependently decreased ethanol intake in all groups except male KO. KO mice were less physically active than WT in cages with or without running wheels. Results suggest that overrepresentation of D2SR contributes to increased intake of ethanol in the KO mice. Decreasing wheel running and general levels of physical activity in the KO mice rules out the possibility that higher intake results from higher motor activity. Results extend the literature implicating altered expression of D2R in risk for addiction by delineating the contribution of individual D2R isoforms. These findings suggest that D2LR and D2SR play differential roles in consumption of alcohol and sugar rewards.

  14. Cyclin D2 Protein Stability Is Regulated in Pancreatic β-Cells

    PubMed Central

    He, Lu Mei; Sartori, Daniel J.; Teta, Monica; Opare-Addo, Lynn M.; Rankin, Matthew M.; Long, Simon Y.; Diehl, J. Alan; Kushner, Jake A.

    2009-01-01

    The molecular determinants of β-cell mass expansion remain poorly understood. Cyclin D2 is the major D-type cyclin expressed in β-cells, essential for adult β-cell growth. We hypothesized that cyclin D2 could be actively regulated in β-cells, which could allow mitogenic stimuli to influence β-cell expansion. Cyclin D2 protein was sharply increased after partial pancreatectomy, but cyclin D2 mRNA was unchanged, suggesting posttranscriptional regulatory mechanisms influence cyclin D2 expression in β-cells. Consistent with this hypothesis, cyclin D2 protein stability is powerfully regulated in fibroblasts. Threonine 280 of cyclin D2 is phosphorylated, and this residue critically limits D2 stability. We derived transgenic (tg) mice with threonine 280 of cyclin D2 mutated to alanine (T280A) or wild-type cyclin D2 under the control of the insulin promoter. Cyclin D2 T280A protein was expressed at much higher levels than wild-type cyclin D2 protein in β-cells, despite equivalent expression of tg mRNAs. Cyclin D2 T280A tg mice exhibited a constitutively nuclear cyclin D2 localization in β-cells, and increased cyclin D2 stability in islets. Interestingly, threonine 280-mutant cyclin D2 tg mice had greatly reduced β-cell apoptosis, with suppressed expression of proapoptotic genes. Suppressed β-cell apoptosis in threonine 280-mutant cyclin D2 tg mice resulted in greatly increased β-cell area in aged mice. Taken together, these data indicate that cyclin D2 is regulated by protein stability in pancreatic β-cells, that signals that act upon threonine 280 limit cyclin D2 stability in β-cells, and that threonine 280-mutant cyclin D2 overexpression prolongs β-cell survival and augments β-cell mass expansion. PMID:19628581

  15. Absolute state-selected total cross sections for the ion-molecule reactions O + (4S,2D,2P)+H2(D2)

    NASA Astrophysics Data System (ADS)

    Li, X.; Huang, Y.-L.; Flesch, G. D.; Ng, C. Y.

    1997-01-01

    Absolute total cross sections for the state-selected reactions of O+(4S,2D,2P)+H2 (D2) have been measured in the center-of-mass collision energy (Ec.m.) range of 0.02-12 eV. The cross sections for OH+ (OD+) from O+(2D)+H2 (D2) are slightly higher than those from O+(4S)+H2 (D2), whereas the OH+ (OD+) cross sections from O+ (2P)+H2 (D2) are ≈40% lower than those from O+(4S)+H2 (D2) and O+ (2D)+H2 (D2). At Ec.m.<0.5 eV, the total cross sections for OH+ (OD+) from O+ (4S)+H2 (D2) and O+(2D)+H2 (D2) are in accord with those predicted by the Langevin-Gioumousis-Stevenson model. Significantly higher cross sections are observed for H+ (D+) and H2+ (D2+) from O+(2D)+H2 (D2) and O+(2P)+H2 (D2), as compared to those from O+(4S)+H2 (D2). The exothermic nature of the O+(2D,2P)+H2 (D2) charge transfer collisions accounts for the high cross sections observed for H2+ (D2+). While the H+ (D+) ions observed in the O+(4S)+H2 (D2) reaction are identified with the H+ (D+)+O+H channel, the H+ (D+) ions from the reactions involving O+(2D) and O+(2P) are associated mostly with the H+ (D+)+OH (OD) channel, the formation of which obeys the spin-conservation rule. The comparison of the sum (σT) of cross sections for OH+ (OD+), H2+ (D2+), and H+ (D+) from O+(4S)+H2 (D2) to those from O+(2D)+H2 (D2) and O+(2P)+H2 (D2) shows that the σTs for O+(4S)+H2 (D2), O+(2D)+H2 (D2), and O+(2P)+H2 (D2) at Ec.m.<0.5 eV are comparable. At Ec.m.>0.5 eV, the σTs for O+(2P)+H2 (D2) are greater than those for O+(2D)+H2 (D2), which in turn are greater than those for O+(4S)+H2 (D2). This observation is attributed to the increase in the number of accessible product channels for reactions involving the excited O+(2D) and O+(2P) reactant ions.

  16. Submillimeter D2O-18 molecular laser with optical pumping

    NASA Astrophysics Data System (ADS)

    Svich, V. A.; Pokormiakho, N. G.; Topkov, A. N.

    1980-11-01

    In the considered investigation, nine new emission lines of the D2O-18 molecule were observed over the wavelength range from 96 to 140 micrometers. In the experiments, a CO2 TEA laser was used for optical pumping. The TEA laser was operated at atmospheric pressure with an output energy up to 2 J and a pulse length of 100 ns. A gaseous mixture with a composition of CO2:N2:He = 1:1:4 was excited by means of a pulsed transverse discharge. A resonator with a length of 1 m was formed by a spherical mirror with a radius of curvature of 10 m, and a gold-plated echelette grating with 100 lines/mm. The submillimeter cell consisted of a glass tube with an inside diameter of 80 mm and a length of 1270 mm, and the spherical mirrors of the submillimeter resonator.

  17. Secondary-Proton Spectra from D_2-Filled OMEGA Targets

    NASA Astrophysics Data System (ADS)

    Séguin, F. H.; Frenje, J. A.; Li, C. K.; Hicks, D. G.; Green, K. M.; Petrasso, R. D.; Glebov, V. Yu.; Stoeckl, C.; Radha, P. B.; Soures, J. M.; Meyerhofer, D. D.; Roberts, S.; Sorce, C.; Sangster, T. C.; Padalino, S.; Fletcher, K.

    2000-10-01

    Spectroscopic measurements of secondary fusion protons of imploded D_2-filled capsules in ICF experiments are now carried out with magnet-based charged-particle spectrometers and with a new type of ``range filter''-based detector utilizing special filters and CR39 nuclear track detectors. The mean proton energy determines the capsule's total areal density (ρR). Measurement of proton yield, in combination with the primary and secondary neutron yield, provides an estimate of fuel parameters. Recent data from OMEGA implosions will be presented. This work was performed in part at the LLE National Laser Users' Facility (NLUF), and was supported in part by the U.S. DOE Contract DE-FG03-99SF21782, LLE subcontract PO410025G, LLNL subcontract B313975, and by the U.S. DOE Office of ICF under Coop. Agreem. No. DE-FC03-92SF19460.

  18. Analysis of [3',3'-d(2)]-nicotine and [3',3'-d(2)]-cotinine by capillary liquid chromatography-electrospray tandem mass spectrometry.

    PubMed

    Murphy, Sharon E; Villalta, Peter; Ho, Sing-Wei; von Weymarn, Linda B

    2007-09-15

    A selective and sensitive LC/MS/MS assay was developed for the quantification of d(2)-nicotine and d(2)-cotinine in plasma of current and past smokers administered d(2)-nicotine. After solid phase extraction and liquid-liquid extraction, HPLC separation was achieved on a capillary hydrophilic interaction chromatography phase column. The analytes were monitored by tandem mass spectrometry with electrospray positive ionization. Linear calibration curves were generated for d(2)-nicotine (0.03-6.0 ng/ml plasma) and d(2)-cotinine (0.15-25 ng/ml plasma). The lower limits of quantitation were 0.15 ng/ml and 0.25 ng/ml for d(2)-nicotine and d(2)-cotinine, respectively. The coefficient of variation was 3.7% for d(2)-nicotine and 2.5% for d(2)-cotinine. The method was applied to two ongoing studies of d(2)-nicotine metabolism in prior and current smokers. Preliminary analysis of a subset of subjects from these studies detected a significantly lower rate of nicotine conversion to cotinine by past smokers compared to current smokers.

  19. Loqs depends on R2D2 to localize in D2 body-like granules and functions in RNAi pathways in silkworm cells.

    PubMed

    Zhu, Li; Tatsuke, Tsuneyuki; Xu, Jian; Li, Zhiqing; Mon, Hiroaki; Lee, Jae Man; Kusakabe, Takahiro

    2015-09-01

    The phenomenon of RNA interference (RNAi) has been found in various organisms. However, the proteins implicated in RNAi pathway in different species show distinct roles. Knowledge on the underlying mechanism of lepidopteron RNAi is quite lacking such as the roles of Loquacious (Loqs) and R2D2, the dsRNA-binding proteins in silkworm RNAi pathway. Here, we report that Loqs and R2D2 protein depletion affected efficiency of dsRNA-mediated RNAi pathway. Besides, Loqs was found to co-localize with Dicer2 to some specific cytoplasmic foci, which were looked like D2-bodies marked by R2D2 and Dicer2 in Fly cells, thereby calling the foci as D2 body-like granules. Using RNAi methods, Loqs was found to be the key protein in these granules, although R2D2 determined the localization of Loqs in D2 body-like granules. Interestingly, in the R2D2-depeted silkworm cells, the formation of processing bodies, another cytoplasmic foci, was affected. These data indicated R2D2 regulated these two kinds of cytoplasmic foci. Domain deletion analysis demonstrated that dsRBD 1 and 2 were required for Loqs in D2 body-like granules and dsRBD 2 and 3 were required for Loqs to interact with R2D2 and Ago1, respectively. Altogether, our observations provide important information for further study on D2 body-like granules, the newly found cytoplasmic foci in silkworm cells.

  20. MOLECULAR DETERMINANTS OF A2AR-D2R ALLOSTERISM: ROLE OF THE INTRACELLULAR LOOP 3 OF THE D2R

    PubMed Central

    Fernández-Dueñas, Víctor; Gómez-Soler, Maricel; Jacobson, Kenneth A.; Kumar, T. Santhosh; Fuxe, Kjell; Borroto-Escuela, Dasiel O.; Ciruela, Francisco

    2012-01-01

    In the central nervous system (CNS), an antagonistic interaction has been shown between adenosine A2A and dopamine D2 receptors (A2ARs and D2Rs) that may be relevant both in normal and pathological conditions (i.e. Parkinson’s disease). Thus, the molecular determinants mediating this receptor-receptor interaction have recently been explored, since the fine tuning of this target (namely the A2AR/D2R oligomer) could possibly improve the treatment of certain CNS diseases. Here, we used a fluorescence resonance energy transfer (FRET)-based approach to examine the allosteric modulation of the D2R within the A2AR/D2R oligomer and the dependence of this receptor-receptor interaction on two regions rich in positive charges on intracellular loop 3 (IL3) of the D2R. Interestingly, we observed a negative allosteric effect of the D2R agonist quinpirole on A2AR ligand binding and activation. However, these allosteric effects were abolished upon mutation of specific arginine residues (217–222 and 267–269) on IL3 of the D2R, thus demonstrating a major role of these positively-charged residues in mediating the observed receptor-receptor interaction. Overall, these results provide structural insights to better understand the functioning of the A2AR/D2R oligomer in living cells. PMID:22924752

  1. Dissociation of D2+ by UV and THz light pulses

    NASA Astrophysics Data System (ADS)

    Xu, Tian-Yu; He, Feng

    2013-10-01

    The dissociation of D2+ in the few-cycle UV and THz light pulses is studied by numerically simulating the time-dependent Schrödinger equation. With only the UV pulse, we find the dissociation probability does not increase monotonously with the increasing of the UV pulse intensity or duration. The UV-triggered dissociation is streaked by the time-delayed THz light pulse, i.e., the nuclear momentum oscillates with the half of the THz period when the UV-THz time delay or the carrier envelope phase of the THz pulse is scanned. The difference of the maximum and minimum nuclear momenta equals the THz laser vector potential. The classical calculation of the Newtonian equation for a mass point moving on the THz light-modified molecular potential curves reproduces the quantum simulation results and therefore intuitively explores the physical scenario: The nuclear wave packets propagate along the THz field-dressed molecular potential curves adiabatically but make a fully diabatic transition, while the THz electric field changes direction. This study offers a visual angle to understand the molecular dissociation in the strong laser field with very long wavelengths.

  2. Higher derivative massive spin-3 models in D =2 +1

    NASA Astrophysics Data System (ADS)

    Dalmazi, D.; Mendonça, E. L.

    2016-07-01

    We find new higher derivative models describing a parity doublet of massive spin-3 modes in D =2 +1 dimensions. One of them is of fourth order in derivatives while the other one is of sixth order. They are complete, in the sense that they contain the auxiliary scalar field required to remove spurious degrees of freedom. Both of them are obtained through the master action technique starting with the usual (second-order) spin-3 Singh-Hagen model, which guarantees that they are ghost free. The fourth- and sixth-order terms are both invariant under (transverse) Weyl transformations, quite similarly to the fourth-order K -term of the "new massive gravity." The sixth-order term slightly differs from the product of the Schouten by the Einstein tensor, both of third order in derivatives. It is also possible to write down the fourth-order term as a product of a Schouten-like by an Einstein-like tensor (both of second order in derivatives) in close analogy with the K -term.

  3. Macroscopic Behavior of Nematics with D2d Symmetry

    NASA Astrophysics Data System (ADS)

    Pleiner, Harald; Brand, Helmut R.

    2010-03-01

    We discuss the symmetry properties and the macroscopic behavior of a nematic liquid crystal phase with D2d symmetry. Such a phase is a prime candidate for nematic phases made from banana-shaped molecules where the usual quadrupolar order coexists with octupolar (tetrahedratic) order. The resulting nematic phase is non-polar. While this phase could resemble the classic D∞h nematic in the polarizing microscope, it has many static as well as reversible and irreversible properties unknown to non-polar nematics without octupolar order. In particular, there is a linear gradient term in the free energy that selects parity leading to ambidextrously helical ground states when the molecules are achiral. In addition, there are static and irreversible coupling terms of a type only met otherwise in macroscopically chiral liquid crystals, e.g. the ambidextrous analogues of Lehmann-type effects known from cholesteric liquid crystals. Finally, we discuss certain nonlinear aspects of the dynamics related to the non-commutativity of three-dimensional finite rotations as well as other structural nonlinear hydrodynamic effects.

  4. Control and imaging of O(1D2) precession.

    PubMed

    Wu, Shiou-Min; Radenovic, Dragana Č; van der Zande, Wim J; Groenenboom, Gerrit C; Parker, David H; Vallance, Claire; Zare, Richard N

    2011-01-01

    Larmor precession of a quantum mechanical angular momentum vector about an applied magnetic field forms the basis for a range of magnetic resonance techniques, including nuclear magnetic resonance spectroscopy and magnetic resonance imaging. We have used a polarized laser pump-probe scheme with velocity-map imaging detection to visualize, for the first time, the precessional motion of a quantum mechanical angular momentum vector. Photodissociation of O(2) at 157 nm provides a clean source of fast-moving O((1)D(2)) atoms, with their electronic angular momentum vector strongly aligned perpendicular to the recoil direction. In the presence of an external magnetic field, the distribution of atomic angular momenta precesses about the field direction, and polarization-sensitive images of the atomic scattering distribution recorded as a function of field strength yield 'time-lapse-photography' style movies of the precessional motion. We present movies recorded in various experimental geometries, and discuss potential consequences and applications in atmospheric chemistry and reaction dynamics.

  5. Effect of C-Terminal S-Palmitoylation on D2 Dopamine Receptor Trafficking and Stability

    PubMed Central

    Ebersole, Brittany; Petko, Jessica; Woll, Matthew; Murakami, Shoko; Sokolina, Kate; Wong, Victoria; Stagljar, Igor; Lüscher, Bernhard; Levenson, Robert

    2015-01-01

    We have used bioorthogonal click chemistry (BCC), a sensitive non-isotopic labeling method, to analyze the palmitoylation status of the D2 dopamine receptor (D2R), a G protein-coupled receptor (GPCR) crucial for regulation of processes such as mood, reward, and motor control. By analyzing a series of D2R constructs containing mutations in cysteine residues, we found that palmitoylation of the D2R most likely occurs on the C-terminal cysteine residue (C443) of the polypeptide. D2Rs in which C443 was deleted showed significantly reduced palmitoylation levels, plasma membrane expression, and protein stability compared to wild-type D2Rs. Rather, the C443 deletion mutant appeared to accumulate in the Golgi, indicating that palmitoylation of the D2R is important for cell surface expression of the receptor. Using the full-length D2R as bait in a membrane yeast two-hybrid (MYTH) screen, we identified the palmitoyl acyltransferase (PAT) zDHHC4 as a D2R interacting protein. Co-immunoprecipitation analysis revealed that several other PATs, including zDHHC3 and zDHHC8, also interacted with the D2R and that each of the three PATs was capable of affecting the palmitoylation status of the D2R. Finally, biochemical analyses using D2R mutants and the palmitoylation blocker, 2-bromopalmitate indicate that palmitoylation of the receptor plays a role in stability of the D2R. PMID:26535572

  6. Prostaglandin D2-loaded microspheres effectively activate macrophage effector functions.

    PubMed

    Pereira, Priscilla Aparecida Tartari; Bitencourt, Claudia da Silva; dos Santos, Daiane Fernanda; Nicolete, Roberto; Gelfuso, Guilherme Martins; Faccioli, Lúcia Helena

    2015-10-12

    Biodegradable lactic-co-glycolic acid (PLGA) microspheres (MS) improve the stability of biomolecules stability and allow enable their sustained release. Lipid mediators represent a strategy for improving host defense; however, most of these mediators, such as prostaglandin D2 (PGD2), have low water solubility and are unstable. The present study aimed to develop and characterize MS loaded with PGD2 (PGD2-MS) to obtain an innovative tool to activate macrophages. PGD2-MS were prepared using an oil-in-water emulsion solvent extraction-evaporation process, and the size, zeta potential, surface morphology and encapsulation efficiency were determined. It was also evaluated in vitro the phagocytic index, NF-κB activation, as well as nitric oxide and cytokine production by alveolar macrophages (AMs) in response to PGD2-MS. PGD2-MS were spherical with a diameter of 5.0±3.3 μm and regular surface, zeta potential of -13.4±5.6 mV, and 36% of encapsulation efficiency, with 16-26% release of entrapped PGD2 at 4 and 48 h, respectively. PGD2-MS were more efficiently internalized by AMs than unloaded-MS, and activated NF-κB more than free PGD2. Moreover, PGD2-MS stimulated the production of nitric oxide, TNF-α, IL-1β, and TGF-β, more than free PGD2, indicating that microencapsulation increased the activating effect of PGD2 on cells. In LPS-pre-treated AMs, PGD2-MS decreased the release of IL-6 but increased the production of nitric oxide and IL-1β. These results show that the morphological characteristics of PGD2-MS facilitated interaction with, and activation of phagocytic cells; moreover, PGD2-MS retained the biological activities of PGD2 to trigger effector mechanisms in AMs. It is suggested that PGD2-MS represent a strategy for therapeutic intervention in the lungs of immunocompromised subjects.

  7. Implantation of Energetic D+ Ions into Carbon Dioxide Ices and Implications for our Solar System: Formation of D2O and D2CO3

    NASA Astrophysics Data System (ADS)

    Bennett, Chris J.; Ennis, Courtney P.; Kaiser, Ralf I.

    2014-10-01

    Carbon dioxide (CO2) ices were irradiated with energetic D+ ions to simulate the exposure of oxygen-bearing solar system ices to energetic protons from the solar wind and magnetospheric sources. The formation of species was observed online and in situ by exploiting FTIR spectroscopy. Molecular products include ozone (O3), carbon oxides (CO3(C 2v , D 3h ), CO4, CO5, CO6), D2-water (D2O), and D2-carbonic acid (D2CO3). Species released into the gas phase were sampled via a quadrupole mass spectrometer, and possible minor contributions from D2-formaldehyde (D2CO), D4-methanol (CD3OD), and D2-formic acid (DCOOD) were additionally identified. The feasibility of several reaction networks was investigated by determining their ability to fit the observed temporal column densities of 10 key species that were quantified during the irradiation period. Directly relevant to the CO2-bearing ices of comets, icy satellites in the outer solar system, and the ice caps on Mars, this work illustrates for the first time that D2-water is formed as a product of the exposure of CO2 ices to D+ ions. These findings provide strong support for water formation from oxygen-bearing materials via non-thermal hydrogen atoms, and predict reaction pathways that are likely to be unfolding on the surfaces of asteroids and the Moon.

  8. 26 CFR 1.643(d)-2 - Illustration of the provisions of section 643.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Illustration of the provisions of section 643. 1.643(d)-2 Section 1.643(d)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Estates, Trusts, and Beneficiaries § 1.643(d)-2...

  9. Preliminary abatement device evaluation: 1D-2D KGM cyclone design

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Cyclones are predominately used in controlling cotton gin particulate matter (PM) emissions. The most commonly used cyclone designs are the 2D-2D and 1D-3D; however other designs such as the 1D-2D KGM have or are currently being used. A 1D-2D cyclone has a barrel length equal to the barrel diamete...

  10. 16 CFR Appendix D2 to Part 305 - Water Heaters-Electric

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 16 Commercial Practices 1 2012-01-01 2012-01-01 false Water Heaters-Electric D2 Appendix D2 to Part 305 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS RULE... Appendix D2 to Part 305—Water Heaters—Electric Range Information CAPACITY FIRST HOUR RATING Range...

  11. 16 CFR Appendix D2 to Part 305 - Water Heaters-Electric

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Water Heaters-Electric D2 Appendix D2 to Part 305 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF CONGRESS RULE... Appendix D2 to Part 305—Water Heaters—Electric Range Information CAPACITY FIRST HOUR RATING Range...

  12. D2HGDH regulates alpha-ketoglutarate levels and dioxygenase function by modulating IDH2

    PubMed Central

    Lin, An-Ping; Abbas, Saman; Kim, Sang-Woo; Ortega, Manoela; Bouamar, Hakim; Escobedo, Yissela; Varadarajan, Prakash; Qin, Yuejuan; Sudderth, Jessica; Schulz, Eduard; Deutsch, Alexander; Mohan, Sumitra; Ulz, Peter; Neumeister, Peter; Rakheja, Dinesh; Gao, Xiaoli; Hinck, Andrew; Weintraub, Susan T.; DeBerardinis, Ralph J.; Sill, Heinz; Dahia, Patricia L. M.; Aguiar, Ricardo C. T.

    2015-01-01

    Isocitrate dehydrogenases (IDH) convert isocitrate to alpha-ketoglutarate (α-KG). In cancer, mutant IDH1/2 reduces α-KG to D2-hydroxyglutarate (D2-HG) disrupting α-KG-dependent dioxygenases. However, the physiological relevance of controlling the interconversion of D2-HG into α-KG, mediated by D2-hydroxyglutarate dehydrogenase (D2HGDH), remains obscure. Here we show that wild-type D2HGDH elevates α-KG levels, influencing histone and DNA methylation, and HIF1α hydroxylation. Conversely, the D2HGDH mutants that we find in diffuse large B-cell lymphoma are enzymatically inert. D2-HG is a low-abundance metabolite, but we show that it can meaningfully elevate α-KG levels by positively modulating mitochondrial IDH activity and inducing IDH2 expression. Accordingly, genetic depletion of IDH2 abrogates D2HGDH effects, whereas ectopic IDH2 rescues D2HGDH-deficient cells. Our data link D2HGDH to cancer and describe an additional role for the enzyme: the regulation of IDH2 activity and α-KG-mediated epigenetic remodelling. These data further expose the intricacies of mitochondrial metabolism and inform on the pathogenesis of D2HGDH-deficient diseases. PMID:26178471

  13. 16 CFR Appendix D2 to Part 305 - Water Heaters-Electric

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Water Heaters-Electric D2 Appendix D2 to... CONCERNING DISCLOSURES REGARDING ENERGY CONSUMPTION AND WATER USE OF CERTAIN HOME APPLIANCES AND OTHER... Appendix D2 to Part 305—Water Heaters—Electric Range Information CAPACITY FIRST HOUR RATING Range...

  14. 16 CFR Appendix D2 to Part 305 - Water Heaters-Electric

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 16 Commercial Practices 1 2013-01-01 2013-01-01 false Water Heaters-Electric D2 Appendix D2 to... CONCERNING DISCLOSURES REGARDING ENERGY CONSUMPTION AND WATER USE OF CERTAIN HOME APPLIANCES AND OTHER... Appendix D2 to Part 305—Water Heaters—Electric Range Information CAPACITY FIRST HOUR RATING Range...

  15. Serum Concentrations of 1,25-Dihydroxyvitamin D2 and 1,25-Dihydroxyvitamin D3 in Response to Vitamin D2 and Vitamin D3 Supplementation

    PubMed Central

    Biancuzzo, Rachael M.; Clarke, Nigel; Reitz, Richard E.; Travison, Thomas G.

    2013-01-01

    Objective: The purpose of this study was to determine 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and 1,25-dihydroxyvitamin D2 [1,25(OH)2D2] levels in healthy adults consuming 1000 IU vitamin D2 or vitamin D3 per day for 11 weeks. Subjects and Design: Blood from 34 healthy male and female adults, aged 18 to 79 years, from a placebo-controlled, double-blind study who received a placebo, 1000 IU vitamin D3, or 1000 IU vitamin D2 daily for 11 weeks at end of winter was analyzed. Serum levels of 25-hydroxyvitamin D2, 25-hydroxyvitamin D3, 1,25(OH)2D2, and 1,25(OH)2D3 were determined by liquid chromatography–tandem mass spectroscopy. Results: Of the adults, 82% were vitamin D insufficient (serum 25-hydroxyvitamin D [25(OH)D <30 ng/mL]) at the start of the study. Administration of vitamin D2 and vitamin D3 induced similar increases in total 25(OH)D as well as in 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3, respectively. Compared with placebo and adjusting for baseline levels, 1000 IU daily of vitamin D2 was associated with a mean increase of 7.4 pg/mL (95% confidence interval, 4.4–10.3) in 1,25(OH)2D2, which was accompanied by a mean decrease of 9.9 pg/mL (−15.8 to −4.0) in 1,25(OH)2D3. No such differences accompanied administration of 1000 IU daily of vitamin D3. Conclusion: Vitamin D2 and vitamin D3 were effective in raising and maintaining total serum concentrations of 25(OH)D. Ingestion of vitamin D2 also resulted in an increase in serum concentrations of 1,25(OH)2D2. This increase was accompanied by a comparable decrease in serum concentrations of 1,25(OH)2D3; therefore, the total 1,25-dihydroxyvitamin D [1,25(OH)2D] concentrations did not significantly change after 11 weeks compared with baseline levels. Ingestion of vitamin D3 did not alter serum concentrations of 1,25(OH)2D3 or total 1,25(OH)2D. Therefore, ingestion of 1000 IU vitamin D2 or vitamin D3 for 11 weeks was effective in raising total serum concentrations of 25(OH)D as well as sustaining serum

  16. Opiate Exposure State Controls a D2-CaMKIIα-Dependent Memory Switch in the Amygdala-Prefrontal Cortical Circuit

    PubMed Central

    Rosen, Laura G; Zunder, Jordan; Renard, Justine; Fu, Jennifer; Rushlow, Walter; Laviolette, Steven R

    2016-01-01

    The mammalian basolateral amygdala (BLA) and medial prefrontal cortex (mPFC) comprise a functionally interconnected circuit that is critical for processing opiate-related associative memories. In the opiate-naïve state, reward memory formation in the BLA involves a functional link between dopamine (DA) D1 receptor (D1R) and extracellular signal-related kinase 1/2 (ERK1/2) signaling substrates, but switches to a DA D2 (D2R)/Ca2+/calmodulin-dependent protein kinase IIα (CaMKIIα)-dependent memory substrate following chronic opiate exposure and spontaneous withdrawal. Using conditioned place preference (CPP) in rats paired with molecular analyses, we examined the role of intra-mPFC CaMKII, ERK and DAergic activity during the formation of opiate associative memories, and how opiate exposure state may regulate the functions of these molecular memory pathways. We report that the role of CaMKIIα signaling is functionally reversed within the BLA-mPFC pathway depending on opiate exposure state. Thus, in the opiate-naïve state, intra-mPFC but not intra-BLA blockade of CaMKII signaling prevents formation of opiate reward memory. However, following chronic opiate exposure and spontaneous withdrawal, the role of CaMKII signaling in the BLA-mPFC is functionally reversed. This behavioral memory switch corresponds to a selective increase in the expression of D2R and CaMKIIα, but not other calcium/calmodulin-related molecules, nor D1R expression levels within the mPFC. PMID:26174594

  17. Thyroid Hormone Signaling in Male Mouse Skeletal Muscle Is Largely Independent of D2 in Myocytes

    PubMed Central

    Werneck-de-Castro, Joao P.; Fonseca, Tatiana L.; Ignacio, Daniele L.; Fernandes, Gustavo W.; Andrade-Feraud, Cristina M.; Lartey, Lattoya J.; Ribeiro, Marcelo B.; Ribeiro, Miriam O.; Gereben, Balazs

    2015-01-01

    The type 2 deiodinase (D2) activates the prohormone T4 to T3. D2 is expressed in skeletal muscle (SKM), and its global inactivation (GLOB-D2KO mice) reportedly leads to skeletal muscle hypothyroidism and impaired differentiation. Here floxed Dio2 mice were crossed with mice expressing Cre-recombinase under the myosin light chain 1f (cre-MLC) to disrupt D2 expression in the late developmental stages of skeletal myocytes (SKM-D2KO). This led to a loss of approximately 50% in D2 activity in neonatal and adult SKM-D2KO skeletal muscle and about 75% in isolated SKM-D2KO myocytes. To test the impact of Dio2 disruption, we measured soleus T3 content and found it to be normal. We also looked at the expression of T3-responsive genes in skeletal muscle, ie, myosin heavy chain I, α-actin, myosin light chain, tropomyosin, and serca 1 and 2, which was preserved in neonatal SKM-D2KO hindlimb muscles, at a time that coincides with a peak of D2 activity in control animals. In adult soleus the baseline level of D2 activity was about 6-fold lower, and in the SKM-D2KO soleus, the expression of only one of five T3-responsive genes was reduced. Despite this, adult SKM-D2KO animals performed indistinguishably from controls on a treadmill test, running for approximately 16 minutes and reached a speed of about 23 m/min; muscle strength was about 0.3 mN/m·g body weight in SKM-D2KO and control ankle muscles. In conclusion, there are multiple sources of D2 in the mouse SKM, and its role is limited in postnatal skeletal muscle fibers. PMID:26214036

  18. Thyroid Hormone Signaling in Male Mouse Skeletal Muscle Is Largely Independent of D2 in Myocytes.

    PubMed

    Werneck-de-Castro, Joao P; Fonseca, Tatiana L; Ignacio, Daniele L; Fernandes, Gustavo W; Andrade-Feraud, Cristina M; Lartey, Lattoya J; Ribeiro, Marcelo B; Ribeiro, Miriam O; Gereben, Balazs; Bianco, Antonio C

    2015-10-01

    The type 2 deiodinase (D2) activates the prohormone T4 to T3. D2 is expressed in skeletal muscle (SKM), and its global inactivation (GLOB-D2KO mice) reportedly leads to skeletal muscle hypothyroidism and impaired differentiation. Here floxed Dio2 mice were crossed with mice expressing Cre-recombinase under the myosin light chain 1f (cre-MLC) to disrupt D2 expression in the late developmental stages of skeletal myocytes (SKM-D2KO). This led to a loss of approximately 50% in D2 activity in neonatal and adult SKM-D2KO skeletal muscle and about 75% in isolated SKM-D2KO myocytes. To test the impact of Dio2 disruption, we measured soleus T3 content and found it to be normal. We also looked at the expression of T3-responsive genes in skeletal muscle, ie, myosin heavy chain I, α-actin, myosin light chain, tropomyosin, and serca 1 and 2, which was preserved in neonatal SKM-D2KO hindlimb muscles, at a time that coincides with a peak of D2 activity in control animals. In adult soleus the baseline level of D2 activity was about 6-fold lower, and in the SKM-D2KO soleus, the expression of only one of five T3-responsive genes was reduced. Despite this, adult SKM-D2KO animals performed indistinguishably from controls on a treadmill test, running for approximately 16 minutes and reached a speed of about 23 m/min; muscle strength was about 0.3 mN/m·g body weight in SKM-D2KO and control ankle muscles. In conclusion, there are multiple sources of D2 in the mouse SKM, and its role is limited in postnatal skeletal muscle fibers.

  19. Prostaglandin D2 Attenuates Bleomycin-Induced Lung Inflammation and Pulmonary Fibrosis

    PubMed Central

    Omori, Keisuke; Nakamura, Tatsuro; Maehara, Toko; Aritake, Kosuke; Urade, Yoshihiro; Murata, Takahisa

    2016-01-01

    Pulmonary fibrosis is a progressive and fatal lung disease with limited therapeutic options. Although it is well known that lipid mediator prostaglandins are involved in the development of pulmonary fibrosis, the role of prostaglandin D2 (PGD2) remains unknown. Here, we investigated whether genetic disruption of hematopoietic PGD synthase (H-PGDS) affects the bleomycin-induced lung inflammation and pulmonary fibrosis in mouse. Compared with H-PGDS naïve (WT) mice, H-PGDS-deficient mice (H-PGDS-/-) represented increased collagen deposition in lungs 14 days after the bleomycin injection. The enhanced fibrotic response was accompanied by an increased mRNA expression of inflammatory mediators, including tumor necrosis factor-α, monocyte chemoattractant protein-1, and cyclooxygenase-2 on day 3. H-PGDS deficiency also increased vascular permeability on day 3 and infiltration of neutrophils and macrophages in lungs on day 3 and 7. Immunostaining showed that the neutrophils and macrophages expressed H-PGDS, and its mRNA expression was increased on day 3and 7 in WT lungs. These observations suggest that H-PGDS-derived PGD2 plays a protective role in bleomycin-induced lung inflammation and pulmonary fibrosis. PMID:27992456

  20. For Earth into space: The German Spacelab Mission D-2

    NASA Astrophysics Data System (ADS)

    Sahm, P. R.; Keller, M. H.; Schiewe, B.

    The Spacelab Mission D-2 successfully lifted off from Kennedy Space Center on April 26, 1993. With 88 experiments on board covering eleven different research disciplines it was a very ambitious mission. Besides materials and life science subjects, the mission also encompassed astronomy, earth observation, radiation physics and biology, telecommunication, automation and robotics. Notable results were obtained in almost all cases. To give some examples of the scientific output, building upon results obtained in previous missions (FSLP, D1) diffusion in melts was broadly represented delivering most precise data on the atomic mobility within various liquids, and crystal growth experiments (the largest gallium arsenide crystal grown by the floating zone technique, so far obtained anywhere, was one of the results), biological cell growth experiments were continued (for example, beer yeast cultures, continuing their growth on earth, delivered a qualitatively superior brewery result), the human physiology miniclinic configuration ANTHRORACK gave novel insights concerning cardiovascular, pulmonary, and renal (fluid volume determining) factors. Astronomical experiments yielded insights into our own galaxy within the ultra violet spectrum, earth observation experiments delivered the most precise resolution data superimposed by thematic mapping of many areas of the Earth, and the robotics experiment brought a remarkable feature in that a flying object was caught by the space robot, which was only achieved through several innovative advances during the time of experiment preparation. The eight years of preparation were also beneficial in another sense. Several discoveries have been made, and various technology transfers into ground-based processes were verified. To name the outstanding ones, in the materials science a novel bearing materials production process was developped, a patent granted for an improved high temperature heating chamber; with life sciences a new hormone

  1. Cryogenic DT and D2 Targets for Inertial Confinement Fusion

    NASA Astrophysics Data System (ADS)

    Sangster, T. C.

    2006-10-01

    Nearly all inertial confinement fusion ignition target designs are based on a spherical ablator containing a solid, cryogenic-DT-fuel layer. The uniformity of the inner surface of this layer is a critical factor in determining target performance. This talk will describe how cryogenic targets are made, characterized, and imploded on the 60-beam OMEGA laser. While cryogenic D2 targets have been routinely imploded for several years, only recently have targets containing DT-fuel layers been possible. Several of these targets have been imploded on OMEGA and most have had inner-ice-surface uniformity between 1- and 2-μm rms (very close to the ignition specification). These are the first laser-imploded targets to be formed exclusively using beta layering. The creation of these high-uniformity DT layers depends on understanding and controlling many diverse physics processes. These include sublimation and condensation at the inner ice surface (the heart of the layering process), phase transitions of multi-isotopic hydrogen ice, heat flow in the ice, heat flow in the exchange gas surrounding the ice, the geometry of the layering sphere that surrounds the target, and the time that the target is exposed to ambient radiation before being irradiated. In addition, a unique optical shadowgraphic technique has been developed to accurately characterize the 3-D ice-layer-thickness distribution for model comparisons and input to multidimensional hydrocode simulations. The talk will be placed in a historical context, describing previous approaches that worked with smaller targets and, more importantly, the approach being followed for the National Ignition Facility (NIF). It will describe the mutual constraints that target-design requirements and cryogenic system practicalities impose upon each other, for both direct and indirect drive, and how lessons learned on OMEGA can be used to improve the prospects for a successful ignition campaign on the NIF. Finally, implosion results from

  2. Increasing dopamine D2 receptor expression in the adult nucleus accumbens enhances motivation

    PubMed Central

    Trifilieff, Pierre; Feng, Bo; Urizar, Eneko; Winiger, Vanessa; Ward, Ryan D.; Taylor, Kathleen M.; Martinez, Diana M.; Moore, Holly; Balsam, Peter D.; Simpson, Eleanor H.; Javitch, Jonathan A.

    2014-01-01

    A decrease in dopamine D2 receptor (D2R) binding in the striatum is one of the most common findings in disorders that involve a dysregulation of motivation, including obesity, addiction, and attention deficit hyperactivity disorder. Since disruption of D2R signaling in the ventral striatum – including the Nucleus Accumbens (NAc) - impairs motivation, we sought to determine whether potentiating postsynaptic D2R-dependent signaling in the NAc would improve motivation. In this study, we used a viral vector strategy to overexpress postsynaptic D2Rs in either the NAc or the dorsal striatum. We investigated the effects of D2R overexpression on instrumental learning, willingness to work, use of reward value representations and modulation of motivation by reward associated cues. Overexpression of postsynaptic D2R in the NAc selectively increased motivation without altering consummatory behavior, the representation of the value of the reinforcer, or the capacity to use reward associated cues in flexible ways. In contrast, D2R overexpression in the dorsal striatum did not alter performance on any of the tasks. Thus, consistent with numerous studies showing that reduced D2R signaling impairs motivated behavior, our data show that post-synaptic D2R overexpression in the NAc specifically increases an animal’s willingness to expend effort to obtain a goal. Taken together, these results provide insight into the potential impact of future therapeutic strategies that enhance D2R signaling in the NAc. PMID:23711983

  3. The dosage of the neuroD2 transcription factor regulates amygdala development and emotional learning

    PubMed Central

    Lin, Chin-Hsing; Hansen, Stacey; Wang, Zhenshan; Storm, Daniel R.; Tapscott, Stephen J.; Olson, James M.

    2005-01-01

    The amygdala is centrally involved in formation of emotional memory and response to fear or risk. We have demonstrated that the lateral and basolateral amygdala nuclei fail to form in neuroD2 null mice and neuroD2 heterozygotes have fewer neurons in this region. NeuroD2 heterozygous mice show profound deficits in emotional learning as assessed by fear conditioning. Unconditioned fear was also diminished in neuroD2 heterozygotes compared to wild-type controls. Several key molecular regulators of emotional learning were diminished in the brains of neuroD2 heterozygotes including Ulip1, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor, and GABAA receptor. Thus, neuroD2 is essential for amygdala development and genes involved in amygdala function are altered in neuroD2-deficient mice. PMID:16203979

  4. Threshold ionization spectroscopy of H2O, HDO and D2O and low-lying vibrational levels of HDO+ and D2O+

    NASA Astrophysics Data System (ADS)

    Lauzin, Clément; Jacovella, Ugo; Merkt, Frédéric

    2015-12-01

    Rotationally resolved photoelectron spectra of jet-cooled H2O, HDO and D2O have been recorded near the origin of the ? photoionising transition following single-photon ionization using the complementary techniques of mass-analysed threshold-ionization (MATI) and pulsed-field-ionization zero-kinetic-energy (PFI-ZEKE) photoelectron spectroscopy. A gas mixture of H2O, HDO and D2O with Ar was obtained by mixing H2O (ℓ) and D2O (ℓ) in a reservoir and bubbling Ar gas through the mixture. To unambiguously assign the photoelectron bands to H2O, HDO or D2O, the PFI-ZEKE photoelectron spectra of the mixture were compared to MATI spectra and to spectra of H2O. Analysis of the rotational structure of the origin bands (v+1 = 0, v2+ = 0, v+3 = 0) ← (v1 = 0, v2 = 0, v3 = 0) of H2O, HDO and D2O and of the transitions to the (010), (020) and (100) levels of D2O+ and the first excited level of the O-D stretching mode of HDO+ provided new information on the photoionization dynamics of water and the energy level structure of HDO+ and D2O+.

  5. Low bioaccessibility of vitamin D2 from yeast-fortified bread compared to crystalline D2 bread and D3 from fluid milks.

    PubMed

    Lipkie, Tristan E; Ferruzzi, Mario G; Weaver, Connie M

    2016-11-09

    The assessment of the efficacy of dietary and supplemental vitamin D tends to be confounded by differences in the serum 25-hydroxyvitamin D response between vitamin D2 and vitamin D3. Serum response differences from these vitamers may be due to differences in bioavailability. To address this specifically, the bioaccessibility was assessed for vitamin D2 from breads fortified with UV-treated yeast, and a benchmark against staple vitamin D3 fortified foods including bovine milks and infant formula, as well as crystalline vitamin D2 fortified bread. Fortified foods were subjected to a three-stage static in vitro digestion model, and vitamin D was analyzed by HPLC-MS. Vitamin D bioaccessibility was significantly greater from bovine milks and infant formula (71-85%) than from yeast-fortified sandwich breads (6-7%). Bioaccessibility was not different between whole wheat and white wheat bread (p > 0.05), but was ∼4× lower from yeast-fortified bread than from crystalline vitamin D2 fortified bread (p < 0.05). Intact yeast cells were observed in the digesta of yeast fortified bread. These results indicate that the low bioavailability of yeast D2 in comparison to other vitamin D2 sources is likely due to entrapment within a less digestible yeast matrix and not only to metabolic differences between vitamins D2 and D3.

  6. Evidence for Noncanonical Neurotransmitter Activation: Norepinephrine as a Dopamine D2-Like Receptor Agonist.

    PubMed

    Sánchez-Soto, Marta; Bonifazi, Alessandro; Cai, Ning Sheng; Ellenberger, Michael P; Newman, Amy Hauck; Ferré, Sergi; Yano, Hideaki

    2016-04-01

    The Gαi/o-coupled dopamine D2-like receptor family comprises three subtypes: the D2 receptor (D2R), with short and long isoform variants (D2SR and D2LR), D3 receptor (D3R), and D4 receptor (D4R), with several polymorphic variants. The common overlap of norepinephrine innervation and D2-like receptor expression patterns prompts the question of a possible noncanonical action by norepinephrine. In fact, previous studies have suggested that norepinephrine can functionally interact with D4R. To our knowledge, significant interactions between norepinephrine and D2R or D3R receptors have not been demonstrated. By using radioligand binding and bioluminescent resonance energy transfer (BRET) assays in transfected cells, the present study attempted a careful comparison between dopamine and norepinephrine in their possible activation of all D2-like receptors, including the two D2R isoforms and the most common D4R polymorphic variants. Functional BRET assays included activation of G proteins with all Gαi/o subunits, adenylyl cyclase inhibition, and β arrestin recruitment. Norepinephrine acted as a potent agonist for all D2-like receptor subtypes, with the general rank order of potency of D3R > D4R ≥ D2SR ≥ D2L. However, for both dopamine and norepinephrine, differences depended on the Gαi/o protein subunit involved. The most striking differences were observed with Gαi2, where the rank order of potencies for both dopamine and norepinephrine were D4R > D2SR = D2LR > D3R. Furthermore the results do not support the existence of differences in the ability of dopamine and norepinephrine to activate different human D4R variants. The potency of norepinephrine for adrenergic α2A receptor was only about 20-fold higher compared with D3R and D4R across the three functional assays.

  7. Evidence for Noncanonical Neurotransmitter Activation: Norepinephrine as a Dopamine D2-Like Receptor Agonist

    PubMed Central

    Sánchez-Soto, Marta; Bonifazi, Alessandro; Cai, Ning Sheng; Ellenberger, Michael P.; Newman, Amy Hauck

    2016-01-01

    The Gαi/o-coupled dopamine D2-like receptor family comprises three subtypes: the D2 receptor (D2R), with short and long isoform variants (D2SR and D2LR), D3 receptor (D3R), and D4 receptor (D4R), with several polymorphic variants. The common overlap of norepinephrine innervation and D2-like receptor expression patterns prompts the question of a possible noncanonical action by norepinephrine. In fact, previous studies have suggested that norepinephrine can functionally interact with D4R. To our knowledge, significant interactions between norepinephrine and D2R or D3R receptors have not been demonstrated. By using radioligand binding and bioluminescent resonance energy transfer (BRET) assays in transfected cells, the present study attempted a careful comparison between dopamine and norepinephrine in their possible activation of all D2-like receptors, including the two D2R isoforms and the most common D4R polymorphic variants. Functional BRET assays included activation of G proteins with all Gαi/o subunits, adenylyl cyclase inhibition, and β arrestin recruitment. Norepinephrine acted as a potent agonist for all D2-like receptor subtypes, with the general rank order of potency of D3R > D4R ≥ D2SR ≥ D2L. However, for both dopamine and norepinephrine, differences depended on the Gαi/o protein subunit involved. The most striking differences were observed with Gαi2, where the rank order of potencies for both dopamine and norepinephrine were D4R > D2SR = D2LR >> D3R. Furthermore the results do not support the existence of differences in the ability of dopamine and norepinephrine to activate different human D4R variants. The potency of norepinephrine for adrenergic α2A receptor was only about 20-fold higher compared with D3R and D4R across the three functional assays. PMID:26843180

  8. Dopamine-Induced Apoptosis of Lactotropes Is Mediated by the Short Isoform of D2 Receptor

    PubMed Central

    Radl, Daniela Betiana; Ferraris, Jimena; Boti, Valeria; Seilicovich, Adriana; Sarkar, Dipak Kumar; Pisera, Daniel

    2011-01-01

    Dopamine, through D2 receptor (D2R), is the major regulator of lactotrope function in the anterior pituitary gland. Both D2R isoforms, long (D2L) and short (D2S), are expressed in lactotropes. Although both isoforms can transduce dopamine signal, they differ in the mechanism that leads to cell response. The administration of D2R agonists, such as cabergoline, is the main pharmacological treatment for prolactinomas, but resistance to these drugs exists, which has been associated with alterations in D2R expression. We previously reported that dopamine and cabergoline induce apoptosis of lactotropes in primary culture in an estrogen-dependent manner. In this study we used an in vivo model to confirm the permissive action of estradiol in the apoptosis of anterior pituitary cells induced by D2R agonists. Administration of cabergoline to female rats induced apoptosis, measured by Annexin-V staining, in anterior pituitary gland from estradiol-treated rats but not from ovariectomized rats. To evaluate the participation of D2R isoforms in the apoptosis induced by dopamine we used lactotrope-derived PR1 cells stably transfected with expression vectors encoding D2L or D2S receptors. In the presence of estradiol, dopamine induced apoptosis, determined by ELISA and TUNEL assay, only in PR1-D2S cells. To study the role of p38 MAPK in apoptosis induced by D2R activation, anterior pituitary cells from primary culture or PR1-D2S were incubated with an inhibitor of the p38 MAPK pathway (SB203850). SB203580 blocked the apoptotic effect of D2R activation in lactotropes from primary cultures and PR1-D2S cells. Dopamine also induced p38 MAPK phosphorylation, determined by western blot, in PR1-D2S cells and estradiol enhanced this effect. These data suggest that, in the presence of estradiol, D2R agonists induce apoptosis of lactotropes by their interaction with D2S receptors and that p38 MAPK is involved in this process. PMID:21464994

  9. Hallucinogenic 5-HT2AR agonists LSD and DOI enhance dopamine D2R protomer recognition and signaling of D2-5-HT2A heteroreceptor complexes.

    PubMed

    Borroto-Escuela, Dasiel O; Romero-Fernandez, Wilber; Narvaez, Manuel; Oflijan, Julia; Agnati, Luigi F; Fuxe, Kjell

    2014-01-03

    Dopamine D2LR-serotonin 5-HT2AR heteromers were demonstrated in HEK293 cells after cotransfection of the two receptors and shown to have bidirectional receptor-receptor interactions. In the current study the existence of D2L-5-HT2A heteroreceptor complexes was demonstrated also in discrete regions of the ventral and dorsal striatum with in situ proximity ligation assays (PLA). The hallucinogenic 5-HT2AR agonists LSD and DOI but not the standard 5-HT2AR agonist TCB2 and 5-HT significantly increased the density of D2like antagonist (3)H-raclopride binding sites and significantly reduced the pKiH values of the high affinity D2R agonist binding sites in (3)H-raclopride/DA competition experiments. Similar results were obtained in HEK293 cells and in ventral striatum. The effects of the hallucinogenic 5-HT2AR agonists on D2R density and affinity were blocked by the 5-HT2A antagonist ketanserin. In a forskolin-induced CRE-luciferase reporter gene assay using cotransfected but not D2R singly transfected HEK293 cells DOI and LSD but not TCB2 significantly enhanced the D2LR agonist quinpirole induced inhibition of CRE-luciferase activity. Haloperidol blocked the effects of both quinpirole alone and the enhancing actions of DOI and LSD while ketanserin only blocked the enhancing actions of DOI and LSD. The mechanism for the allosteric enhancement of the D2R protomer recognition and signalling observed is likely mediated by a biased agonist action of the hallucinogenic 5-HT2AR agonists at the orthosteric site of the 5-HT2AR protomer. This mechanism may contribute to the psychotic actions of LSD and DOI and the D2-5-HT2A heteroreceptor complex may thus be a target for the psychotic actions of hallunicogenic 5-HT2A agonists.

  10. Flap loop of GluD2 binds to Cbln1 and induces presynaptic differentiation.

    PubMed

    Kuroyanagi, Tomoaki; Hirano, Tomoo

    2010-07-30

    Glutamate receptor delta2 (GluD2) is selectively expressed on the postsynaptic spines at parallel-fiber (PF)-Purkinje neuron (PN) synapses. GluD2 knockout mice show a reduced number of PF-PN synapses, suggesting that GluD2 is involved in synapse formation. Recent studies revealed that GluD2 induces presynaptic differentiation in a manner dependent on its N-terminal domain (NTD) through binding of Cbln1 secreted from cerebellar granule neurons. However, the underlying mechanism of the specific binding of the NTD to Cbln1 remains elusive. Here, we have identified the flap loop (Arg321-Trp339) in the NTD of GluD2 (GluD2-NTD) as a crucial region for the binding to Cbln1 and the induction of presynaptic differentiation. Both induction of presynaptic differentiation and binding of Cbln1 were abolished in the HEK cells expressing not wild-type GluD2 but GluD2 with mutations in the flap loop. Especially, single amino acid substitution of either Arg321 or Trp323 to alanine was sufficient to disable the GluD2 function. Finally, a homology model of GluD2-NTD suggested that the flap loop is located at the distal end, which appears consistent with an interaction with Cbln1 and a presynaptic varicosity.

  11. Blockade of neuronal dopamine D2 receptor attenuates morphine tolerance in mice spinal cord

    PubMed Central

    Dai, Wen-Ling; Xiong, Feng; Yan, Bing; Cao, Zheng-Yu; Liu, Wen-Tao; Liu, Ji-Hua; Yu, Bo-Yang

    2016-01-01

    Tolerance induced by morphine remains a major unresolved problem and significantly limits its clinical use. Recent evidences have indicated that dopamine D2 receptor (D2DR) is likely to be involved in morphine-induced antinociceptive tolerance. However, its exact effect and molecular mechanism remain unknown. In this study we examined the effect of D2DR on morphine antinociceptive tolerance in mice spinal cord. Chronic morphine treatment significantly increased levels of D2DR in mice spinal dorsal horn. And the immunoreactivity of D2DR was newly expressed in neurons rather than astrocytes or microglia both in vivo and in vitro. Blockade of D2DR with its antagonist (sulpiride and L-741,626, i.t.) attenuated morphine antinociceptive tolerance without affecting basal pain perception. Sulpiride (i.t.) also down-regulated the expression of phosphorylation of NR1, PKC, MAPKs and suppressed the activation of astrocytes and microglia induced by chronic morphine administration. Particularly, D2DR was found to interact with μ opioid receptor (MOR) in neurons, and chronic morphine treatment enhanced the MOR/D2DR interactions. Sulpiride (i.t.) could disrupt the MOR/D2DR interactions and attenuate morphine tolerance, indicating that neuronal D2DR in the spinal cord may be involved in morphine tolerance possibly by interacting with MOR. These results may present new opportunities for the treatment and management of morphine-induced antinociceptive tolerance which often observed in clinic. PMID:28004735

  12. Dopamine D2 receptor availability is linked to hippocampal–caudate functional connectivity and episodic memory

    PubMed Central

    Nyberg, Lars; Karalija, Nina; Salami, Alireza; Andersson, Micael; Wåhlin, Anders; Kaboovand, Neda; Köhncke, Ylva; Axelsson, Jan; Rieckmann, Anna; Papenberg, Goran; Garrett, Douglas D.; Riklund, Katrine; Lövdén, Martin; Bäckman, Lars

    2016-01-01

    D1 and D2 dopamine receptors (D1DRs and D2DRs) may contribute differently to various aspects of memory and cognition. The D1DR system has been linked to functions supported by the prefrontal cortex. By contrast, the role of the D2DR system is less clear, although it has been hypothesized that D2DRs make a specific contribution to hippocampus-based cognitive functions. Here we present results from 181 healthy adults between 64 and 68 y of age who underwent comprehensive assessment of episodic memory, working memory, and processing speed, along with MRI and D2DR assessment with [11C]raclopride and PET. Caudate D2DR availability was positively associated with episodic memory but not with working memory or speed. Whole-brain analyses further revealed a relation between hippocampal D2DR availability and episodic memory. Hippocampal and caudate D2DR availability were interrelated, and functional MRI-based resting-state functional connectivity between the ventral caudate and medial temporal cortex increased as a function of caudate D2DR availability. Collectively, these findings indicate that D2DRs make a specific contribution to hippocampus-based cognition by influencing striatal and hippocampal regions, and their interactions. PMID:27339132

  13. Sequential hydroxylation of vitamin D2 by a genetically engineered CYP105A1.

    PubMed

    Hayashi, Keiko; Yasuda, Kaori; Yogo, Yuya; Takita, Teisuke; Yasukawa, Kiyoshi; Ohta, Miho; Kamakura, Masaki; Ikushiro, Shinichi; Sakaki, Toshiyuki

    2016-05-13

    Our previous studies revealed that the double variants of CYP105A1- R73A/R84A and R73V/R84A-show high levels of activity with respect to conversion of vitamin D3 to its biologically active form, 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3). In this study, we found that both the double variants were also capable of converting vitamin D2 to its active form, that is, 1α,25-dihydroxyvitamin D2 (1α,25(OH)2D2), via 25(OH)D2, whereas its 1α-hydroxylation activity toward 25(OH)D2 was much lower than that toward 25(OH)D3. Comparison of the wild type and the double variants revealed that the amino acid substitutions remarkably enhanced both 25- and 26-hydroxylation activity toward vitamin D2. After 25-hydroxylation of vitamin D2, further hydroxylation at C26 may occur frequently without the release of 25(OH)D2 from the substrate-binding pocket. Thus, the double variants of CYP105A1 are quite useful to produce 25,26(OH)2D2 that is one of the metabolites of vitamin D2 detected in human serum.

  14. Dopamine D2 receptors in striatal output neurons enable the psychomotor effects of cocaine

    PubMed Central

    Kharkwal, Geetika; Radl, Daniela; Lewis, Robert; Borrelli, Emiliana

    2016-01-01

    The psychomotor effects of cocaine are mediated by dopamine (DA) through stimulation of striatal circuits. Gabaergic striatal medium spiny neurons (MSNs) are the only output of this pivotal structure in the control of movements. The majority of MSNs express either the DA D1 or D2 receptors (D1R, D2R). Studies have shown that the motor effect of cocaine depends on the DA-mediated stimulation of D1R-expressing MSNs (dMSNs), which is mirrored at the cellular level by stimulation of signaling pathways leading to phosphorylation of ERKs and induction of c-fos. Nevertheless, activation of dMSNs by cocaine is necessary but not sufficient, and D2R signaling is required for the behavioral and cellular effects of cocaine. Indeed, cocaine motor effects and activation of signaling in dMSNs are blunted in mice with the constitutive knockout of D2R (D2RKO). Using mouse lines with a cell-specific knockout of D2R either in MSNs (MSN-D2RKO) or in dopaminergic neurons (DA-D2RKO), we show that D2R signaling in MSNs is required and permissive for the motor stimulant effects of cocaine and the activation of signaling in dMSNs. MSN-D2RKO mice show the same phenotype as constitutive D2RKO mice both at the behavioral and cellular levels. Importantly, activation of signaling in dMSNs by cocaine is rescued by intrastriatal injection of the GABA antagonist, bicuculline. These results are in support of intrastriatal connections of D2R+-MSNs (iMSNs) with dMSNs and indicate that D2R signaling in MSNs is critical for the function of intrastriatal circuits. PMID:27671625

  15. Regulation of cyclin D2 gene expression by the Myc/Max/Mad network: Myc-dependent TRRAP recruitment and histone acetylation at the cyclin D2 promoter

    PubMed Central

    Bouchard, Caroline; Dittrich, Oliver; Kiermaier, Astrid; Dohmann, Karen; Menkel, Annette; Eilers, Martin; Lüscher, Bernhard

    2001-01-01

    Myc oncoproteins promote cell cycle progression in part through the transcriptional up-regulation of the cyclin D2 gene. We now show that Myc is bound to the cyclin D2 promoter in vivo. Binding of Myc induces cyclin D2 expression and histone acetylation at a single nucleosome in a MycBoxII/TRRAP-dependent manner. Down-regulation of cyclin D2 mRNA expression in differentiating HL60 cells is preceded by a switch of promoter occupancy from Myc/Max to Mad/Max complexes, loss of TRRAP binding, increased HDAC1 binding, and histone deacetylation. Thus, recruitment of TRRAP and regulation of histone acetylation are critical for transcriptional activation by Myc. PMID:11511535

  16. Results of an attempt to measure increased rates of the reaction D-2 + D-2 yields He-3 + n in a nonelectrochemical cold fusion experiment

    NASA Technical Reports Server (NTRS)

    Fralick, Gustave C.; Decker, Arthur J.; Blue, James W.

    1989-01-01

    An experiment was performed to look for evidence of deuterium fusion in palladium. The experiment, which involved introducing deuterium into the palladium filter of a hydrogen purifier, was designed to detect neutrons produced in the reaction D-2 + D-2 yields He-3 + n as well as heat production. The neutron counts for deuterium did not differ significantly from background or from the counts for a hydrogen control. Heat production was detected when deuterium, but not hydrogen, was pumped from the purifier.

  17. Multiple D2 heteroreceptor complexes: new targets for treatment of schizophrenia

    PubMed Central

    Borroto-Escuela, Dasiel O.; Pintsuk, Julia; Schäfer, Thorsten; Friedland, Kristina; Ferraro, Luca; Tanganelli, Sergio; Liu, Fang; Fuxe, Kjell

    2016-01-01

    The dopamine (DA) neuron system most relevant for schizophrenia is the meso-limbic-cortical DA system inter alia densely innervating subcortical limbic regions. The field of dopamine D2 receptors and schizophrenia changed markedly with the discovery of many types of D2 heteroreceptor complexes in subcortical limbic areas as well as the dorsal striatum. The results indicate that the D2 is a hub receptor which interacts not only with many other G protein-coupled receptors (GPCRs) including DA isoreceptors but also with ion-channel receptors, receptor tyrosine kinases, scaffolding proteins and DA transporters. Disturbances in several of these D2 heteroreceptor complexes may contribute to the development of schizophrenia through changes in the balance of diverse D2 homo- and heteroreceptor complexes mediating the DA signal, especially to the ventral striato-pallidal γ-aminobutyric acid (GABA) pathway. This will have consequences for the control of this pathway of the glutamate drive to the prefrontal cortex via the mediodorsal thalamic nucleus which can contribute to psychotic processes. Agonist activation of the A2A protomer in the A2A–D2 heteroreceptor complex inhibits D2 Gi/o mediated signaling but increases the D2 β-arrestin2 mediated signaling. Through this allosteric receptor–receptor interaction, the A2A agonist becomes a biased inhibitory modulator of the Gi/o mediated D2 signaling, which may the main mechanism for its atypical antipsychotic properties especially linked to the limbic A2A–D2 heterocomplexes. The DA and glutamate hypotheses of schizophrenia come together in the signal integration in D2–N-methyl-d-aspartate (NMDA) and A2A–D2–metabotropic glutamate receptor 5 (mGlu5) heteroreceptor complexes, especially in the ventral striatum. 5-Hydroxytryptamine 2A (5-HT2A)–D2 heteroreceptor complexes are special targets for atypical antipsychotics with high potency to block their 5-HT2A protomer signaling in view of the potential development of

  18. Dopamine D3/D2 Receptor Antagonist PF-4363467 Attenuates Opioid Drug-Seeking Behavior without Concomitant D2 Side Effects.

    PubMed

    Wager, Travis T; Chappie, Thomas; Horton, David; Chandrasekaran, Ramalakshmi Y; Samas, Brian; Dunn-Sims, Elizabeth R; Hsu, Cathleen; Nawreen, Nawshaba; Vanase-Frawley, Michelle A; O'Connor, Rebecca E; Schmidt, Christopher J; Dlugolenski, Keith; Stratman, Nancy C; Majchrzak, Mark J; Kormos, Bethany L; Nguyen, David P; Sawant-Basak, Aarti; Mead, Andy N

    2017-01-18

    Dopamine receptor antagonism is a compelling molecular target for the treatment of a range of psychiatric disorders, including substance use disorders. From our corporate compound file, we identified a structurally unique D3 receptor (D3R) antagonist scaffold, 1. Through a hybrid approach, we merged key pharmacophore elements from 1 and D3 agonist 2 to yield the novel D3R/D2R antagonist PF-4363467 (3). Compound 3 was designed to possess CNS drug-like properties as defined by its CNS MPO desirability score (≥4/6). In addition to good physicochemical properties, 3 exhibited low nanomolar affinity for the D3R (D3 Ki = 3.1 nM), good subtype selectivity over D2R (D2 Ki = 692 nM), and high selectivity for D3R versus other biogenic amine receptors. In vivo, 3 dose-dependently attenuated opioid self-administration and opioid drug-seeking behavior in a rat operant reinstatement model using animals trained to self-administer fentanyl. Further, traditional extrapyramidal symptoms (EPS), adverse side effects arising from D2R antagonism, were not observed despite high D2 receptor occupancy (RO) in rodents, suggesting that compound 3 has a unique in vivo profile. Collectively, our data support further investigation of dual D3R and D2R antagonists for the treatment of drug addiction.

  19. Vitamin D2, Ergosterol, and Vitamin B2 Content in Commercially Dried Mushrooms Marketed in China and Increased Vitamin D2 Content Following UV-C Irradiation.

    PubMed

    Huang, Guocheng; Cai, Weixi; Xu, Baojun

    2016-11-21

    Mushrooms are a great source of vitamin D and vitamin B2; however, the content of these vitamins in dried mushrooms has not fully been investigated. Thus, the objectives of this study were to determine the contents of vitamin D2, ergosterol, and vitamin B2 in commercially dried edible mushrooms in China and to investigate the effect of UV-C irradiation on fresh mushrooms. Among the 35 species of dried mushrooms considered for this study, the average ergosterol content was 1.98 mg/g, while the average vitamin D2 content was 16.88 µg/g. The average vitamin B2 content in dried mushrooms was 12.68 µg/g. Fresh shaggy ink caps and oyster mushrooms, when exposed to UV-C at 254 nm at a dose of 0.25 J/cm(2) for 10, 30, and 60 min, showed significantly (p < 0.05) increased vitamin D2 content (229.7 and 67.0 µg/g, respectively) as compared to its fresh counterparts. The conversion of ergosterol to vitamin D2 induced by UV-C irradiation at 0.25 J/cm(2) was significant (p < 0.05). In conclusion, dried commercial mushrooms have higher contents of ergosterol and vitamin D2 than fresh mushrooms. UV-C radiation can be used to increase vitamin D2 content in mushrooms.

  20. Effect of pd and dd reactions enhancement in deuterides TiD2, ZrD2 and Ta2D in the astrophysical energy range

    NASA Astrophysics Data System (ADS)

    Bystritskii, V. M.; Dudkin, G. N.; Filipowicz, M.; Huran, J.; Krylov, A. R.; Nechayev, B. A.; Padalko, V. N.; Pen'kov, F. M.; Philippov, A. V.; Tuleushev, Yu. Zh.

    2016-01-01

    Investigation of the pd-and dd-reactions in the ultralow energy (~keV) range is of great interest in the aspect of nuclear physics and astrophysics for developing of correct models of burning and evolution of stars. This report presents compendium of experimental results obtained at the pulsed plasma Hall accelerator (TPU, Tomsk). Most of those results are new, such as • temperature dependence of the neutron yield in the D( d, n)3He reaction in the ZrD2, Ta2D, TiD2 • potentials of electron screening and respective dependence of astrophysical S-factors in the dd-reaction for the deuteron collision energy in the range of 3-6 keV, with ZrD2, Ta2D temperature in the range of 20-200°C [1] • characteristics of the reaction d( p, γ)3He in the ultralow collision proton-deuterons energy range of 4-13 keV [2, 3] in ZrD2, Ta2D and TiD2 • observation of the neutron yield enhancement in the reaction D( d, n)3He at the ultralow deuteron collision energy due to channeling of deuterons in microscopic TiD2 with a face-centered cubic lattice type TiD1.73, oriented in the [100] direction [4]. The report includes discussion and comparison of the collected experimental results with the global data and calculations.

  1. Activation of D2 dopamine receptor-expressing neurons in the nucleus accumbens increases motivation.

    PubMed

    Soares-Cunha, Carina; Coimbra, Barbara; David-Pereira, Ana; Borges, Sonia; Pinto, Luisa; Costa, Patricio; Sousa, Nuno; Rodrigues, Ana J

    2016-06-23

    Striatal dopamine receptor D1-expressing neurons have been classically associated with positive reinforcement and reward, whereas D2 neurons are associated with negative reinforcement and aversion. Here we demonstrate that the pattern of activation of D1 and D2 neurons in the nucleus accumbens (NAc) predicts motivational drive, and that optogenetic activation of either neuronal population enhances motivation in mice. Using a different approach in rats, we further show that activating NAc D2 neurons increases cue-induced motivational drive in control animals and in a model that presents anhedonia and motivational deficits; conversely, optogenetic inhibition of D2 neurons decreases motivation. Our results suggest that the classic view of D1-D2 functional antagonism does not hold true for all dimensions of reward-related behaviours, and that D2 neurons may play a more prominent pro-motivation role than originally anticipated.

  2. Activation of D2 dopamine receptor-expressing neurons in the nucleus accumbens increases motivation

    PubMed Central

    Soares-Cunha, Carina; Coimbra, Barbara; David-Pereira, Ana; Borges, Sonia; Pinto, Luisa; Costa, Patricio; Sousa, Nuno; Rodrigues, Ana J.

    2016-01-01

    Striatal dopamine receptor D1-expressing neurons have been classically associated with positive reinforcement and reward, whereas D2 neurons are associated with negative reinforcement and aversion. Here we demonstrate that the pattern of activation of D1 and D2 neurons in the nucleus accumbens (NAc) predicts motivational drive, and that optogenetic activation of either neuronal population enhances motivation in mice. Using a different approach in rats, we further show that activating NAc D2 neurons increases cue-induced motivational drive in control animals and in a model that presents anhedonia and motivational deficits; conversely, optogenetic inhibition of D2 neurons decreases motivation. Our results suggest that the classic view of D1–D2 functional antagonism does not hold true for all dimensions of reward-related behaviours, and that D2 neurons may play a more prominent pro-motivation role than originally anticipated. PMID:27337658

  3. The Implementation of C-ID, R2D2 Model on Learning Reading Comprehension

    ERIC Educational Resources Information Center

    Rayanto, Yudi Hari; Rusmawan, Putu Ngurah

    2016-01-01

    The purposes of this research are to find out, (1) whether C-ID, R2D2 model is effective to be implemented on learning Reading comprehension, (2) college students' activity during the implementation of C-ID, R2D2 model on learning Reading comprehension, and 3) college students' learning achievement during the implementation of C-ID, R2D2 model on…

  4. ISCCP-D2like-Day Terra Ed3A

    Atmospheric Science Data Center

    2017-03-15

    ISCCP-D2like-Day Terra Ed3A Project Title:  CERES Discipline:  ... Earthdata Search Guide Documents:  Day/Nit Description/Abstract Detailed CERES ISCCP-D2like Product ... Data Products Catalog:  DPC_ISCCP-D2like-Day-Nit_R5V3  (PDF) Readme Files:  Readme Day-Nit ...

  5. Antineoplastic Agents. 565. Synthesis of Combretastatin D-2 Phosphate and Dihydro-combretastatin D-21

    PubMed Central

    Pettit, George R.; Quistorf, Peter D.; Fry, Jeremy A.; Herald, Delbert L.; Hamel, Ernest; Chapuis, Jean-Charles

    2009-01-01

    A modified synthetic route to combretastatin D-2 (5) was devised in order to further evaluate its biological activity, for its conversion to phosphate prodrugs (25–28), and as a route to obtaining dihydro-combretastatin D-2 (42). A parallel first total synthesis of dihydro-combretastatin D-2 was completed, proceeding from a saturated 3-phenylpropionic ester intermediate via the Ullmann biaryl ether reaction (39–41). In contrast to the cancer cell growth inhibitory activity exhibited by combretastatin D-2, relatively minor structural modifications (41, 42) caused elimination of those properties. PMID:20161135

  6. Prolactin plasma levels and D2-dopamine receptor occupancy measured with IBZM-SPECT.

    PubMed

    Schlegel, S; Schlösser, R; Hiemke, C; Nickel, O; Bockisch, A; Hahn, K

    1996-04-01

    By the application of 123([123I]IBZM), an iodine-labelled dopamine D2-receptor antagonist, brain D2 receptors in humans can be visualized with single photon emission computed tomography (SPECT). The ratio of IBZM binding to striatal regions versus binding to frontal cortex (ST/FC ratio) provided a semiquantitative measurement of D2 receptor binding in the striatum. This study investigated the relationship between receptor occupancy and plasma prolactin levels in 12 male patients treated with haloperidol, benperidol or clozapine. Prolactin levels were positively correlated with D2 receptor occupancy, reflecting at least in part a comparable dopamine receptor antagonism in different dopaminergic pathways.

  7. PNA-Based Multivalent Scaffolds Activate the Dopamine D2 Receptor

    PubMed Central

    2015-01-01

    Peptide nucleic acid scaffolds represent a promising tool to interrogate the multivalent effects of ligand binding to a membrane receptor. Dopamine D2 receptors (D2R) are a class of G-protein coupled receptors (GPCRs), and the formation of higher-ordered structures of these receptors has been associated with the progression of several neurological diseases. In this Letter, we describe the synthesis of a library of ligand-modified PNAs bearing a known D2R agonist, (±)-PPHT. The D2R activity for each construct was assessed, and the multivalent effects were evaluated. PMID:25893044

  8. Protein Kinase C Beta Regulates the D2-Like Dopamine Autoreceptor

    PubMed Central

    Luderman, Kathryn D.; Chen, Rong; Ferris, Mark J.; Jones, Sara R.; Gnegy, Margaret E.

    2014-01-01

    The focus of this study was the regulation of the D2-like dopamine autoreceptor (D2 autoreceptor) by protein kinase Cβ, a member of the protein kinase C (PKC) family. Together with the dopamine transporter, the D2 autoreceptor regulates the level of extracellular dopamine and thus dopaminergic signaling. PKC regulates neuronal signaling via several mechanisms, including desensitizing autoreceptors to increase the release of several different neurotransmitters. Here, using both PKCβ−/− mice and specific PKCβ inhibitors, we demonstrated that a lack of PKCβ activity enhanced the D2 autoreceptor-stimulated decrease in dopamine release following both chemical and electrical stimulations. Inhibition of PKCβ increased surface localization of D2R in mouse striatal synaptosomes, which could underlie the greater sensitivity to quinpirole following inhibition of PKCβ. PKCβ−/− mice displayed greater sensitivity to the quinpirole-induced suppression of locomotor activity, demonstrating that the regulation of the D2 autoreceptor by PKCβ is physiologically significant. Overall, we have found that PKCβ downregulates the D2 autoreceptor, providing an additional layer of regulation for dopaminergic signaling. We propose that in the absence of PKCβ activity, surface D2 autoreceptor localization and thus D2 autoreceptor signaling is increased, leading to less dopamine in the extracellular space and attenuated dopaminergic signaling. PMID:25446677

  9. Experimental Studies on the Formation of D2O and D2O2 by Implantation of Energetic D+ Ions into Oxygen Ices

    NASA Astrophysics Data System (ADS)

    Bennett, Chris J.; Ennis, Courtney P.; Kaiser, Ralf I.

    2014-02-01

    The formation of water (H2O) in the interstellar medium is intrinsically linked to grain-surface chemistry; thought to involve reactions between atomic (or molecular) hydrogen with atomic oxygen (O), molecular oxygen (O2), and ozone (O3). Laboratory precedent suggests that H2O is produced efficiently when O2 ices are exposed to H atoms (~100 K). This leads to the sequential generation of the hydroxyperoxyl radical (HO2), then hydrogen peroxide (H2O2), and finally H2O and a hydroxyl radical (OH); despite a barrier of ~2300 K for the last step. Recent detection of the four involved species toward ρ Oph A supports this general scenario; however, the precise formation mechanism remains undetermined. Here, solid O2 ice held at 12 K is exposed to a monoenergetic beam of 5 keV D+ ions. Products formed during the irradiation period are monitored through FTIR spectroscopy. O3 is observed through seven archetypal absorptions. Three additional bands found at 2583, 2707, and 1195 cm -1 correspond to matrix isolated DO2 (ν1) and D2O2 (ν1, ν5), and D2O (ν2), respectively. During subsequent warming, the O2 ice sublimates, revealing a broad band at 2472 cm-1 characteristic of amorphous D2O (ν1, ν3). Sublimating D2, D2O, D2O2, and O3 products were confirmed through their subsequent detection via quadrupole mass spectrometry. Reaction schemes based on both thermally accessible and suprathermally induced chemistries were developed to fit the observed temporal profiles are used to elucidate possible reaction pathways for the formation of D2-water. Several alternative schemes to the hydrogenation pathway (O2→HO2→H2O2→H2O) were identified; their astrophysical implications are briefly discussed.

  10. Effects of repeated treatment with the dopamine D2/D3 receptor partial agonist aripiprazole on striatal D2/D3 receptor availability in monkeys

    PubMed Central

    Czoty, Paul W.; Gage, H. Donald; Garg, Pradeep K.; Garg, Sudha; Nader, Michael A.

    2013-01-01

    Rationale Chronic treatment with dopamine (DA) receptor agonists and antagonists can differentially affect measures of DA D2/D3 receptor number and function, but the effects of chronic treatment with a partial D2/D3 receptor agonist are not clear. Objective We used a within-subjects design in male cynomolgus monkeys to determine the effects of repeated (17-day) treatment with the D2/D3 receptor partial agonist aripiprazole (ARI; 0.03 mg/kg and 0.1 mg/kg i.m.) on food-reinforced behavior (n=5) and on D2/D3 receptor availability as measured with positron emission tomography (PET; n=9). Methods Five monkeys responded under a fixed-ratio 50 schedule of food reinforcement and D2/D3 receptor availability was measured before and four days after ARI treatment using PET and the D2/D3 receptor-selective radioligand [18F]fluoroclebopride (FCP). Four additional monkeys were studied using [11C]raclopride and treated sequentially with each dose of ARI for 17 days. Results ARI decreased food-maintained responding with minimal evidence of tolerance. Repeated ARI administration increased FCP and raclopride distribution volume ratios (DVRs) in the caudate nucleus and putamen in most monkeys, but decreases were observed in monkeys with the highest baseline DVRs. Conclusions The results indicate that repeated treatment with a low efficacy DA receptor partial agonist produces effects on brain D2/D3 receptor availability that are qualitatively different from those of both high-efficacy receptor agonists and antagonists, and suggest that the observed individual differences in response to ARI treatment may reflect its partial agonist activity. PMID:24077804

  11. Metabolic-Activity-Based Assessment of Antimicrobial Effects by D2O-Labeled Single-Cell Raman Microspectroscopy.

    PubMed

    Tao, Yifan; Wang, Yun; Huang, Shi; Zhu, Pengfei; Huang, Wei E; Ling, Junqi; Xu, Jian

    2017-04-04

    To combat the spread of antibiotic resistance, methods that quantitatively assess the metabolism-inhibiting effects of drugs in a rapid and culture-independent manner are urgently needed. Here using four oral bacteria as models, we show that heavy water (D2O)-based single-cell Raman microspectroscopy (D2O-Raman) can probe bacterial response to different drugs using the Raman shift at the C-D (carbon-deuterium vibration) band in 2040 to 2300 cm(-1) as a universal biomarker for metabolic activity at single-bacterial-cell resolution. The "minimum inhibitory concentration based on metabolic activity" (MIC-MA), defined as the minimal dose under which the median ΔC-D-ratio at 8 h of drug exposure is ≤0 and the standard deviation (SD) of the ΔC-D ratio among individual cells is ≤0.005, was proposed to evaluate the metabolism-inhibiting efficacy of drugs. In addition, heterogeneity index of MIC-MA (MIC-MA-HI), defined as SD of C-D ratio among individual cells, quantitatively assesses the among-cell heterogeneity of metabolic activity after drug regimens. When exposed to 1× MIC of sodium fluoride (NaF), 1× MIC of chlorhexidine (CHX), or 60× MIC of ampicillin, the cariogenic oral pathogen Streptococcus mutans UA159 ceased propagation yet remained metabolically highly active. This underscores the advantage of MIC-MA over the growth-based MIC in being able to detect the "nongrowing but metabolically active" (NGMA) cells that underlie many latent or recurring infections. Moreover, antibiotic susceptible and resistant S. mutans strains can be readily discriminated at as early as 0.5 h. Thus, D2O-Raman can serve as a universal method for rapid and quantitative assessment of antimicrobial effects based on general metabolic activity at single-cell resolution.

  12. Reduced sleep duration mediates decreases in striatal D2/D3 receptor availability in cocaine abusers

    PubMed Central

    Wiers, C E; Shumay, E; Cabrera, E; Shokri-Kojori, E; Gladwin, T E; Skarda, E; Cunningham, S I; Kim, S W; Wong, T C; Tomasi, D; Wang, G-J; Volkow, N D

    2016-01-01

    Neuroimaging studies have documented reduced striatal dopamine D2/D3 receptor (D2/D3R) availability in cocaine abusers, which has been associated with impaired prefrontal activity and vulnerability for relapse. However, the mechanism(s) underlying the decreases in D2/D3R remain poorly understood. Recent studies have shown that sleep deprivation is associated with a downregulation of striatal D2/D3R in healthy volunteers. As cocaine abusers have disrupted sleep patterns, here we investigated whether reduced sleep duration mediates the relationship between cocaine abuse and low striatal D2/D3R availability. We used positron emission tomography with [11C]raclopride to measure striatal D2/D3R availability in 24 active cocaine abusers and 21 matched healthy controls, and interviewed them about their daily sleep patterns. Compared with controls, cocaine abusers had shorter sleep duration, went to bed later and reported longer periods of sleep disturbances. In addition, cocaine abusers had reduced striatal D2/D3R availability. Sleep duration predicted striatal D2/D3R availability and statistically mediated the relationship between cocaine abuse and striatal D2/D3R availability. These findings suggest that impaired sleep patterns contribute to the low striatal D2/D3R availability in cocaine abusers. As sleep impairments are similarly observed in other types of substance abusers (for example, alcohol and methamphetamine), this mechanism may also underlie reductions in D2/D3R availability in these groups. The current findings have clinical implications suggesting that interventions to improve sleep patterns in cocaine abusers undergoing detoxification might be beneficial in improving their clinical outcomes. PMID:26954979

  13. Dexamethasone Induces Cardiomyocyte Terminal Differentiation via Epigenetic Repression of Cyclin D2 Gene.

    PubMed

    Gay, Maresha S; Dasgupta, Chiranjib; Li, Yong; Kanna, Angela; Zhang, Lubo

    2016-08-01

    Dexamethasone treatment of newborn rats inhibited cardiomyocyte proliferation and stimulated premature terminal differentiation of cardiomyocytes in the developing heart. Yet mechanisms remain undetermined. The present study tested the hypothesis that the direct effect of glucocorticoid receptor-mediated epigenetic repression of cyclin D2 gene in the cardiomyocyte plays a key role in the dexamethasone-mediated effects in the developing heart. Cardiomyocytes were isolated from 2-day-old rats. Cells were stained with a cardiomyocyte marker α-actinin and a proliferation marker Ki67. Cyclin D2 expression was evaluated by Western blot and quantitative real-time polymerase chain reaction. Promoter methylation of CcnD2 was determined by methylated DNA immunoprecipitation (MeDIP). Overexpression of Cyclin D2 was conducted by transfection of FlexiCcnD2 (+CcnD2) construct. Treatment of cardiomyocytes isolated from newborn rats with dexamethasone for 48 hours significantly inhibited cardiomyocyte proliferation with increased binucleation and decreased cyclin D2 protein abundance. These effects were blocked with Ru486 (mifepristone). In addition, the dexamethasone treatment significantly increased cyclin D2 gene promoter methylation in newborn rat cardiomyocytes. 5-Aza-2'-deoxycytidine inhibited dexamethasone-mediated promoter methylation, recovered dexamethasone-induced cyclin D2 gene repression, and blocked the dexamethasone-elicited effects on cardiomyocyte proliferation and binucleation. In addition, the overexpression of cyclin D2 restored the dexamethasone-mediated inhibition of proliferation and increase in binucleation in newborn rat cardiomyocytes. The results demonstrate that dexamethasone acting on glucocorticoid receptors has a direct effect and inhibits proliferation and stimulates premature terminal differentiation of cardiomyocytes in the developing heart via epigenetic repression of cyclin D2 gene.

  14. D-2-hydroxyglutarate metabolism is linked to photorespiration in the shm1-1 mutant.

    PubMed

    Kuhn, A; Engqvist, M K M; Jansen, E E W; Weber, A P M; Jakobs, C; Maurino, V G

    2013-07-01

    The Arabidopsis mutant shm1-1 is defective in mitochondrial serine hydroxymethyltransferase 1 activity and displays a lethal photorespiratory phenotype at ambient CO2 concentration but grows normally at high CO2 . After transferring high CO2 -grown shm1-1 plants to ambient CO2 , the younger leaves remain photosynthetically active while developed leaves display increased yellowing and decreased FV /FM values. Metabolite analysis of plants transferred from high CO2 to ambient air indicates a massive light-dependent (photorespiratory) accumulation of glycine, 2-oxoglutarate (2OG) and D-2-hydroxyglutarate (D-2HG). Amino acid markers of senescence accumulated in ambient air in wild-type and shm1-1 plants maintained in darkness and also build up in shm1-1 in the light. This, together with an enhanced transcription of the senescence marker SAG12 in shm1-1, suggests the initiation of senescence in shm1-1 under photorespiratory conditions. Mitochondrial D-2HG dehydrogenase (D-2HGDH) converts D-2HG into 2OG. In vitro studies indicate that 2OG exerts competitive inhibition on D-2HGDH with a Ki of 1.96 mm. 2OG is therefore a suitable candidate as inhibitor of the in vivo D-2HGDH activity, as 2OG is produced and accumulates in mitochondria. Inhibition of the D-2HGDH by 2OG is likely a mechanism by which D-2HG accumulates in shm1-1, however it cannot be ruled out that D-2HG may also accumulate due to an active senescence programme that is initiated in these plants after transfer to photorespiratory conditions. Thus, a novel interaction of the photorespiratory pathway with cellular processes involving D-2HG has been identified.

  15. Revisiting the hydration structure of aqueous Na().

    PubMed

    Galib, M; Baer, M D; Skinner, L B; Mundy, C J; Huthwelker, T; Schenter, G K; Benmore, C J; Govind, N; Fulton, J L

    2017-02-28

    A combination of theory, X-ray diffraction (XRD) and extended x-ray absorption fine structure (EXAFS) are used to probe the hydration structure of aqueous Na(+). The high spatial resolution of the XRD measurements corresponds to Qmax = 24 Å(-1) while the first-reported Na K-edge EXAFS measurements have a spatial resolution corresponding to 2k = Qmax = 16 Å(-1). Both provide an accurate measure of the shape and position of the first peak in the Na-O pair distribution function, gNaO(r). The measured Na-O distances of 2.384 ± 0.003 Å (XRD) and 2.37 ± 0.024 Å (EXAFS) are in excellent agreement. These measurements show a much shorter Na-O distance than generally reported in the experimental literature (Na-Oavg ∼ 2.44 Å) although the current measurements are in agreement with recent neutron diffraction measurements. The measured Na-O coordination number from XRD is 5.5 ± 0.3. The measured structure is compared with both classical and first-principles density functional theory (DFT) simulations. Both of the DFT-based methods, revPBE and BLYP, predict a Na-O distance that is too long by about 0.05 Å with respect to the experimental data (EXAFS and XRD). The inclusion of dispersion interactions (-D3 and -D2) significantly worsens the agreement with experiment by further increasing the Na-O distance by 0.07 Å. In contrast, the use of a classical Na-O Lennard-Jones potential with SPC/E water accurately predicts the Na-O distance as 2.39 Å although the Na-O peak is over-structured with respect to experiment.

  16. SD-D2 "Swadana" Upgrading Program [D2 PGSD Swandana]. Summary Preliminary Report, D2-PGSD Program Economic Aspects [and] Report on Study of Economic Aspects. Educational Policy and Planning Project.

    ERIC Educational Resources Information Center

    Cobbe, James; Musa, Ibrahim

    The first of the two reports contained in this document is a preliminary analysis, by Dr. James Cobbe, of the data collected on an extension of a study of the upgrading program for primary school (Sekolah Dasar, or SD) to Diploma Dua (D2) using the Swadana (fully self-financed) delivery system. The extension of the study covers the six current…

  17. Dopamine D2High receptors measured ex vivo are elevated in amphetamine-sensitized animals.

    PubMed

    Seeman, Philip

    2009-03-01

    Although dopamine supersensitivity is a fundamental aspect of diseases such as schizophrenia and Parkinson's disease, the molecular basis of dopamine supersensitivity is not known. Because behavioral dopamine supersensitivity is associated with a marked elevation of striatal dopamine D2(High) receptors in vitro, it is important to develop methods to measure D2(High) receptors in vivo. The present ex vivo study found that the dopamine agonist NPA ([-]-N-propyl-norapomorphine) inhibited the binding of the agonist [(3)H](+)PHNO to rat striatal D2 receptors significantly more than the D2 antagonist [(3)H]raclopride, when NPA was coinjected i.v. with each radioligand. These results suggest that the greater sensitivity of [(3)H](+)PHNO to inhibition by the coinjected NPA reflects in vivo competition at D2(High) receptors. Using rats that had been sensitized to amphetamine, this ex vivo method found that the specific binding of [(3)H](+)PHNO that was displaced by 10 microg/kg of NPA was 2.4-fold higher than that for control rats. These data agree with in vitro data showing a marked increase in D2(High) sites after amphetamine sensitization. Therefore, it is recommended that this method of co-injecting the D2 radioligand and the dopamine agonist displacer be used in human positron tomography to detect D2(High) receptors in health and disease.

  18. 26 CFR 1.643(d)-2 - Illustration of the provisions of section 643.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 8 2012-04-01 2012-04-01 false Illustration of the provisions of section 643. 1.643(d)-2 Section 1.643(d)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... Illustration of the provisions of section 643. (a) The provisions of section 643 may be illustrated by...

  19. 26 CFR 1.643(d)-2 - Illustration of the provisions of section 643.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 8 2013-04-01 2013-04-01 false Illustration of the provisions of section 643. 1.643(d)-2 Section 1.643(d)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... Illustration of the provisions of section 643. (a) The provisions of section 643 may be illustrated by...

  20. 26 CFR 1.643(d)-2 - Illustration of the provisions of section 643.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 8 2014-04-01 2014-04-01 false Illustration of the provisions of section 643. 1.643(d)-2 Section 1.643(d)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... Illustration of the provisions of section 643. (a) The provisions of section 643 may be illustrated by...

  1. 26 CFR 1.643(d)-2 - Illustration of the provisions of section 643.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 8 2011-04-01 2011-04-01 false Illustration of the provisions of section 643. 1.643(d)-2 Section 1.643(d)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... Illustration of the provisions of section 643. (a) The provisions of section 643 may be illustrated by...

  2. UvrD2 is essential in Mycobacterium tuberculosis, but its helicase activity is not required.

    PubMed

    Williams, Alan; Güthlein, Carolin; Beresford, Nicola; Böttger, Erik C; Springer, Burkhard; Davis, Elaine O

    2011-09-01

    UvrD is an SF1 family helicase involved in DNA repair that is widely conserved in bacteria. Mycobacterium tuberculosis has two annotated UvrD homologues; here we investigate the role of UvrD2. The uvrD2 gene at its native locus could be knocked out only in the presence of a second copy of the gene, demonstrating that uvrD2 is essential. Analysis of the putative protein domain structure of UvrD2 shows a distinctive domain architecture, with an extended C terminus containing an HRDC domain normally found in SF2 family helicases and a linking domain carrying a tetracysteine motif. Truncated constructs lacking the C-terminal domains of UvrD2 were able to compensate for the loss of the chromosomal copy, showing that these C-terminal domains are not essential. Although UvrD2 is a functional helicase, a mutant form of the protein lacking helicase activity was able to permit deletion of uvrD2 at its native locus. However, a mutant protein unable to hydrolyze ATP or translocate along DNA was not able to compensate for lack of the wild-type protein. Therefore, we concluded that the essential role played by UvrD2 is unlikely to involve its DNA unwinding activity and is more likely to involve DNA translocation and, possibly, protein displacement.

  3. 17 CFR 240.12d2-2 - Removal from listing and registration.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... on its Web site until the delisting is effective. (2) A national securities exchange must promptly... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Removal from listing and registration. 240.12d2-2 Section 240.12d2-2 Commodity and Securities Exchanges SECURITIES AND...

  4. 17 CFR 240.14d-2 - Commencement of a tender offer.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Commencement of a tender offer. 240.14d-2 Section 240.14d-2 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, SECURITIES EXCHANGE ACT OF 1934 Rules and Regulations Under...

  5. Antiparkinson therapeutic potencies correlate with their affinities at dopamine D2(High) receptors.

    PubMed

    Seeman, Philip

    2007-12-01

    To determine whether antiparkinson dopamine agonists preferentially act on the high-affinity or the low-affinity states of dopamine D1 and D2 receptors, the agonist potencies were obtained by competition against [(3)H]SCH23390 for D1(High) and D1(Low), and against [(3)H]domperidone for D2(High) and D2(Low). N-propylnorapomorphine and cabergoline were the most potent at D2(High), with dissociation constants of 0.18 and 0.36 nM, respectively. Other agonists had D2(High)K(i) values of 0.52 nM for quinagolide, 0.6 nM for (+)PHNO, 0.9 for bromocriptine, 1.8 nM for apomorphine, 2.4 nM for pergolide, 3 nM for quinpirole, and 6.2 nM for lergotrile. There was a clear correlation between the K(i) values at D2(High) and their therapeutic concentrations in the plasma water, as derived from the known concentrations after correction for the fraction bound to the human plasma proteins. The data suggest that D2(High) is the primary and common target for the antiparkinson action of dopamine agonists. Bromocriptine, cabergoline, lergotrile, pergolide, and pramipexole had no affinity for D1(High), consistent with the clinical observations that the D2-selective bromocriptine and pramipexole elicit low levels of dyskinesia.

  6. 17 CFR 240.17d-2 - Program for allocation of regulatory responsibility.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 17 Commodity and Securities Exchanges 3 2010-04-01 2010-04-01 false Program for allocation of regulatory responsibility. 240.17d-2 Section 240.17d-2 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) GENERAL RULES AND REGULATIONS, SECURITIES EXCHANGE ACT OF 1934 Rules...

  7. Discovery, Optimization, and Characterization of Novel D2 Dopamine Receptor Selective Antagonists

    PubMed Central

    2015-01-01

    The D2 dopamine receptor (D2 DAR) is one of the most validated drug targets for neuropsychiatric and endocrine disorders. However, clinically approved drugs targeting D2 DAR display poor selectivity between the D2 and other receptors, especially the D3 DAR. This lack of selectivity may lead to undesirable side effects. Here we describe the chemical and pharmacological characterization of a novel D2 DAR antagonist series with excellent D2 versus D1, D3, D4, and D5 receptor selectivity. The final probe 65 was obtained through a quantitative high-throughput screening campaign, followed by medicinal chemistry optimization, to yield a selective molecule with good in vitro physical properties, metabolic stability, and in vivo pharmacokinetics. The optimized molecule may be a useful in vivo probe for studying D2 DAR signal modulation and could also serve as a lead compound for the development of D2 DAR-selective druglike molecules for the treatment of multiple neuropsychiatric and endocrine disorders. PMID:24666157

  8. High affinity dopamine D2 receptor radioligands. 2. ( sup 125 I)epidepride, a potent and specific radioligand for the characterization of striatal and extrastriatal dopamine D2 receptors

    SciTech Connect

    Kessler, R.M.; Ansari, M.S.; Schmidt, D.E.; de Paulis, T.; Clanton, J.A.; Manning, R.G.; Gillespie, D. ); Innis, R.; Al-Tikriti, M. )

    1991-01-01

    Epidepride, (S)-N-((1-ethyl-2-pyrrolidinyl)methyl)-5-iodo-2,3-dimethoxybenzamide, the iodine analogue of isoremoxipride (FLB 457), was found to be a very potent dopamine D2 receptor antagonist. Optimal in vitro binding required incubation at 25C for 4 h at pH 7.4 in a buffer containing 120 mM NaCl, 5 mM KCl, 2 mM CaCl{sub 2} and 1 nM MgCl{sub 2}. Scatchard analysis of in vitro binding to striatal, medical frontal cortical, hippocampal and cerebellar membranes revealed a K{sub D} of 24 pM in all regions, with Bmax's of 36.7, 1.04, 0.85, and 0.37 pmol/g tissue, respectively. The Hill coefficients ranged from 0.91-1.00 in all four regions. The IC{sub 50}'s for inhibition of ({sup 125}I)epidepride binding to striatal, medial frontal cortical, and hippocampal membranes for SCH 23390, SKF 83566, serotonin, ketanserin, mianserin, naloxone, QNB, prasozin, clonidine, alprenolol, and norepinephrine ranged from 1 {mu}M to >10 {mu}M. Partial displacement of ({sup 125}I)epidepride by nanomolar concentrations of clonidine was noted in the frontal cortex and hippocampus, but not in the striatum. Scatchard analysis of epidepride binding to {alpha}{sub 2} noradrenergic receptors in the frontal cortex and hippocampus revealed an apparent K{sub D} of 9 nM. At an epidepride concentration equal to the K{sub D} for the D2 receptor, i.e., 25 pM, no striatal {alpha}{sub 2} binding was seen and only 7% of the specific epidepride binding in the cortex or hippocampus was due to binding at the {alpha}{sub 2} site. Correlation of inhibition of ({sup 3}H)spiperone and ({sup 125}I)epidepride binding to striatal membranes by a variety of D2 ligands revealed a correlation coefficient of 0.99, indicating that epidepride labels a D2 site.

  9. Regulation of dopamine D2 receptors in a novel cell line (SUP1)

    SciTech Connect

    Ivins, K.J.; Luedtke, R.R.; Artymyshyn, R.P.; Molinoff, P.B. )

    1991-04-01

    A prolactin-secreting cell line, SUP1, has been established from rat pituitary tumor 7315a. In radioligand binding experiments, the D2 receptor antagonist (S)-(-)-3-{sup 125}I iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2- pyrrolidinyl)methyl)benzamide ({sup 125}I IBZM) labeled a single class of sites in homogenates of SUP1 cells (Kd = 0.6 nM; Bmax = 45 fmol/mg of protein). The sites displayed a pharmacological profile consistent with that of D2 receptors. Inhibition of the binding of {sup 125}I IBZM by dopamine was sensitive to GTP, suggesting that D2 receptors in SUP1 cells are coupled to guanine nucleotide-binding protein(s). In the presence of isobutylmethylxanthine, dopamine decreased the level of cAMP accumulation in SUP1 cells. Dopamine also inhibited prolactin secretion from SUP1 cells. Both the inhibition of cAMP accumulation and the inhibition of prolactin secretion were blocked by D2 receptor antagonists, suggesting that these effects of dopamine were mediated by an interaction with D2 receptors. The regulation of D2 receptors in SUP1 cells by D2 receptor agonists was investigated. Exposure of SUP1 cells to dopamine or to the D2 receptor agonist N-propylnorapomorphine led to increased expression of D2 receptors, with no change in the affinity of the receptors for {sup 125}I IBZM. An increase in the density of D2 receptors in SUP1 cells was evident within 7 hr of exposure to dopamine. Spiroperidol, a D2 receptor antagonist, blocked the effect of dopamine on receptor density. These results suggest that exposure of D2 receptors in SUP1 cells to agonists leads to an up-regulation of D2 receptors. Dopamine retained the ability to inhibit cAMP accumulation in SUP1 cells exposed to dopamine for 24 hr, suggesting that D2 receptors in SUP1 cells are not desensitized by prolonged exposure to agonist.

  10. Dopamine D2 receptors regulate the anatomical and functional balance of basal ganglia circuitry.

    PubMed

    Cazorla, Maxime; de Carvalho, Fernanda Delmondes; Chohan, Muhammad O; Shegda, Mariya; Chuhma, Nao; Rayport, Stephen; Ahmari, Susanne E; Moore, Holly; Kellendonk, Christoph

    2014-01-08

    Structural plasticity in the adult brain is essential for adaptive behavior. We have found a remarkable anatomical plasticity in the basal ganglia of adult mice that is regulated by dopamine D2 receptors (D2Rs). By modulating neuronal excitability, striatal D2Rs bidirectionally control the density of direct pathway collaterals in the globus pallidus that bridge the direct pathway with the functionally opposing indirect pathway. An increase in bridging collaterals is associated with enhanced inhibition of pallidal neurons in vivo and disrupted locomotor activation after optogenetic stimulation of the direct pathway. Chronic blockade with haloperidol, an antipsychotic medication used to treat schizophrenia, decreases the extent of bridging collaterals and rescues the locomotor imbalance. These findings identify a role for bridging collaterals in regulating the concerted balance of striatal output and may have important implications for understanding schizophrenia, a disease involving excessive activation of striatal D2Rs that is treated with D2R blockers.

  11. The dopamine D2 receptor is expressed in GH3 cells.

    PubMed

    Johnston, J M; Wood, D F; Bolaji, E A; Johnston, D G

    1991-10-01

    Some pituitary tumours respond to dopamine by decreasing the release of prolactin and/or GH and by inhibition of tumour growth. Certain tumours are unresponsive. Dopamine D2 receptor high-affinity binding is impaired in these tumours, and the rat GH3 cell line behaves in a similar way. The hypothesis that the dopamine-binding defect results from impaired D2 receptor gene expression has been tested in the present study. On Northern blots, D2 receptor mRNA was present in both normal rat pituitary cells and in GH3 cells. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis identified a putative D2 receptor protein in normal and GH3 cell membranes. The lack of effect of dopamine in GH3 cells does not reflect the absence of D2 receptor gene expression.

  12. The dopamine D2 receptor gene in lamprey, its expression in the striatum and cellular effects of D2 receptor activation.

    PubMed

    Robertson, Brita; Huerta-Ocampo, Icnelia; Ericsson, Jesper; Stephenson-Jones, Marcus; Pérez-Fernández, Juan; Bolam, J Paul; Diaz-Heijtz, Rochellys; Grillner, Sten

    2012-01-01

    All basal ganglia subnuclei have recently been identified in lampreys, the phylogenetically oldest group of vertebrates. Furthermore, the interconnectivity of these nuclei is similar to mammals and tyrosine hydroxylase-positive (dopaminergic) fibers have been detected within the input layer, the striatum. Striatal processing is critically dependent on the interplay with the dopamine system, and we explore here whether D2 receptors are expressed in the lamprey striatum and their potential role. We have identified a cDNA encoding the dopamine D2 receptor from the lamprey brain and the deduced protein sequence showed close phylogenetic relationship with other vertebrate D2 receptors, and an almost 100% identity within the transmembrane domains containing the amino acids essential for dopamine binding. There was a strong and distinct expression of D2 receptor mRNA in a subpopulation of striatal neurons, and in the same region tyrosine hydroxylase-immunoreactive synaptic terminals were identified at the ultrastructural level. The synaptic incidence of tyrosine hydroxylase-immunoreactive boutons was highest in a region ventrolateral to the compact layer of striatal neurons, a region where most striatal dendrites arborise. Application of a D2 receptor agonist modulates striatal neurons by causing a reduced spike discharge and a diminished post-inhibitory rebound. We conclude that the D2 receptor gene had already evolved in the earliest group of vertebrates, cyclostomes, when they diverged from the main vertebrate line of evolution (560 mya), and that it is expressed in striatum where it exerts similar cellular effects to that in other vertebrates. These results together with our previous published data (Stephenson-Jones et al. 2011, 2012) further emphasize the high degree of conservation of the basal ganglia, also with regard to the indirect loop, and its role as a basic mechanism for action selection in all vertebrates.

  13. The dopaminergic stabilizer ASP2314/ACR16 selectively interacts with D2(High) receptors.

    PubMed

    Seeman, Philip; Tokita, Kenichi; Matsumoto, Mitsuyuki; Matsuo, Ayako; Sasamata, Masao; Miyata, Keiji

    2009-10-01

    Dopaminergic stabilizers are recognized as compounds that can either enhance or antagonize dopamine (DA)-dependent behaviors depending on the prevailing dopaminergic tone. The dopaminergic stabilizer ASP2314 is being tested clinically and has been reported to have antipsychotic effects in a clinical trial as an add on medication. To elucidate the mechanisms of action of this dopaminergic stabilizer, its potency on the functional dopamine D2(High) receptors was examined. In competition with D2 receptors selectively labeled by [3H]domperidone, ASP2314 had a dissociation constant, Ki(High), of 1.62 microM for D2(High) in human cloned D2Long receptors and 0.83 muM for rat homogenized striata. Using the D2 agonist ligand [3H](+)-4-propyl-3,4,4a,5,6,10b-hexahydro-2H-naphtho[1,2-b][1,4]oxazin-9-ol ((+)PHNO), ASP2314 had a high-affinity Ki of 32 nM for D2(High) for rat homogenized striata. ASP2314 stimulated the incorporation of [35S]GTP-gamma-S into rat striata by 50% at 43 nM, and into the cloned D2Long membranes by 50% at 3.2 microM (compared to 100% stimulation by 10 microM dopamine). With similar concentrations of ASP2314 inhibiting the binding of ligands at D2(High) and stimulating [35S]GTP-gamma-S incorporation, the data indicate that the dopaminergic stabilizing action of ASP2314 may be related to the selectivity for the D2(high) state of the D2 receptor.

  14. Tctex1d2 Is a Negative Regulator of GLUT4 Translocation and Glucose Uptake.

    PubMed

    Shimoda, Yoko; Okada, Shuichi; Yamada, Eijiro; Pessin, Jeffrey E; Yamada, Masanobu

    2015-10-01

    Tctex1d2 (Tctex1 domain containing 2) is an open reading frame that encodes for a functionally unknown protein that contains a Tctex1 domain found in dynein light chain family members. Examination of gene expression during adipogenesis demonstrated a marked increase in Tctex1d2 protein expression that was essentially undetectable in preadipocytes and markedly induced during 3T3-L1 adipocyte differentiation. Tctex1d2 overexpression significantly inhibited insulin-stimulated glucose transporter 4 (GLUT4) translocation and 2-deoxyglucose uptake. In contrast, Tctex1d2 knockdown significantly increased insulin-stimulated GLUT4 translocation and 2-deoxyglucose uptake. However, acute insulin stimulation (up to 30 min) in 3T3-L1 adipocytes with overexpression or knockdown of Tctex1d2 had no effect on Akt phosphorylation, a critical signal transduction target required for GLUT4 translocation. Although overexpression of Tctex1d2 had no significant effect on GLUT4 internalization, Tctex1d2 was found to associate with syntaxin 4 in an insulin-dependent manner and inhibit Doc2b binding to syntaxin 4. In addition, glucose-dependent insulinotropic polypeptide rescued the Tctex1d2 inhibition of insulin-stimulated GLUT4 translocation by suppressing the Tctex1d2-syntaxin 4 interaction and increasing Doc2b-Synatxin4 interactions. Taking these results together, we hypothesized that Tctex1d2 is a novel syntaxin 4 binding protein that functions as a negative regulator of GLUT4 plasma membrane translocation through inhibition of the Doc2b-syntaxin 4 interaction.

  15. Identification of resolvin D2 receptor mediating resolution of infections and organ protection

    PubMed Central

    Chiang, Nan; Dalli, Jesmond; Colas, Romain A.

    2015-01-01

    Endogenous mechanisms that orchestrate resolution of acute inflammation are essential in host defense and the return to homeostasis. Resolvin (Rv)D2 is a potent immunoresolvent biosynthesized during active resolution that stereoselectively stimulates resolution of acute inflammation. Here, using an unbiased G protein–coupled receptor-β-arrestin–based screening and functional sensing systems, we identified a receptor for RvD2, namely GPR18, that is expressed on human leukocytes, including polymorphonuclear neutrophils (PMN), monocytes, and macrophages (MΦ). In human MΦ, RvD2-stimulated intracellular cyclic AMP was dependent on GPR18. RvD2-stimulated phagocytosis of Escherichia coli and apoptotic PMN (efferocytosis) were enhanced with GPR18 overexpression and significantly reduced by shRNA knockdown. Specific binding of RvD2 to recombinant GPR18 was confirmed using a synthetic 3H-labeled-RvD2. Scatchard analysis gave a Kd of ∼10 nM consistent with RvD2 bioactive concentration range. In both E. coli and Staphylococcus aureus infections, RvD2 limited PMN infiltration, enhanced phagocyte clearance of bacteria, and accelerated resolution. These actions were lost in GPR18-deficient mice. During PMN-mediated second organ injury, RvD2’s protective actions were also significantly diminished in GPR18-deficient mice. Together, these results provide evidence for a novel RvD2–GPR18 resolution axis that stimulates human and mouse phagocyte functions to control bacterial infections and promote organ protection. PMID:26195725

  16. Modulation of dopamine D(2) receptor signaling by actin-binding protein (ABP-280).

    PubMed

    Li, M; Bermak, J C; Wang, Z W; Zhou, Q Y

    2000-03-01

    Proteins that bind to G protein-coupled receptors have recently been identified as regulators of receptor anchoring and signaling. In this study, actin-binding protein 280 (ABP-280), a widely expressed cytoskeleton-associated protein that plays an important role in regulating cell morphology and motility, was found to associate with the third cytoplasmic loop of dopamine D(2) receptors. The specificity of this interaction was originally identified in a yeast two-hybrid screen and confirmed by protein binding. The functional significance of the D(2) receptor-ABP-280 association was evaluated in human melanoma cells lacking ABP-280. D(2) receptor agonists were less potent in inhibiting forskolin-stimulated cAMP production in these cells. Maximal inhibitory responses of D(2) receptor activation were also reduced. Further yeast two-hybrid experiments showed that ABP-280 association is critically dependent on the carboxyl domain of the D(2) receptor third cytoplasmic loop, where there is a potential serine phosphorylation site (S358). Serine 358 was replaced with aspartic acid to mimic the effects of receptor phosphorylation. This mutant (D(2)S358D) displayed compromised binding to ABP-280 and coupling to adenylate cyclase. PKC activation also generated D(2) receptor signaling attenuation, but only in ABP-containing cells, suggesting a PKC regulatory role in D(2)-ABP association. A mechanism for these results may be derived from a role of ABP-280 in the clustering of D(2) receptors, as determined by immunocytochemical analysis in ABP-deficient and replete cells. Our results suggest a new molecular mechanism of modulating D(2) receptor signaling by cytoskeletal protein interaction.

  17. Intermolecular potential and rovibrational states of the H2O-D2 complex

    NASA Astrophysics Data System (ADS)

    van der Avoird, Ad; Scribano, Yohann; Faure, Alexandre; Weida, Miles J.; Fair, Joanna R.; Nesbitt, David J.

    2012-05-01

    A five-dimensional intermolecular potential for H2O-D2 was obtained from the full nine-dimensional ab initio potential surface of Valiron et al. [P. Valiron, M. Wernli, A. Faure, L. Wiesenfeld, C. Rist, S. Kedžuch, J. Noga, J. Chem. Phys. 129 (2008) 134306] by averaging over the ground state vibrational wave functions of H2O and D2. On this five-dimensional potential with a well depth De of 232.12 cm-1 we calculated the bound rovibrational levels of H2O-D2 for total angular momentum J = 0-3. The method used to compute the rovibrational levels is similar to a scattering approach—it involves a basis of coupled free rotor wave functions for the hindered internal rotations and the overall rotation of the dimer—while it uses a discrete variable representation of the intermolecular distance coordinate R. The basis was adapted to the permutation symmetry associated with the para/ortho (p/o) nature of both H2O and D2, as well as to inversion symmetry. As expected, the H2O-D2 dimer is more strongly bound than its H2O-H2 isotopologue [cf. A. van der Avoird, D.J. Nesbitt, J. Chem. Phys. 134 (2011) 044314], with dissociation energies D0 of 46.10, 50.59, 67.43, and 73.53 cm-1 for pH2O-oD2, oH2O-oD2, pH2O-pD2, and oH2O-pD2. A rotationally resolved infrared spectrum of H2O-D2 was measured in the frequency region of the H2O bend mode. The ab initio calculated values of the rotational and distortion constants agree well with the values extracted from this spectrum.

  18. Evidence that antipsychotic drugs are inverse agonists at D2 dopamine receptors.

    PubMed

    Hall, D A; Strange, P G

    1997-06-01

    1. The effects of a number of D2-like dopamine receptor antagonists have been determined on forskolin-stimulated cyclic AMP accumulation in Chinese hamster ovary (CHO) cells expressing the human D2short dopamine receptor (CHO-D2S cells). 2. Dopamine inhibited the effect of forskolin (as expected for a D2 receptor). However, all of the antagonists tested, apart from UH232 and (-)-butaclamol, were able to increase cyclic AMP accumulation above the forskolin control level. (+)-Butaclamol elicited a similar stimulation of forskolin-stimulated cyclic AMP accumulation in a CHO cell line expressing human D2long dopamine receptors whereas it exhibited no stimulating effect on forskolin-stimulated cyclic AMP accumulation in untransfected CHO-K1 cells. 3. There was a strong correlation between the EC50 values of these compounds for potentiation of cyclic AMP accumulation and their Ki values from radioligand binding experiments in CHO-D2S cells. 4. The effects of both (+)-butaclamol and dopamine in CHO-D2S cells were inhibited by pre-treatment with pertussis toxin indicating a role for Gi/Go proteins. 5. UH232 did not significantly affect forskolin-stimulated cyclic AMP accumulation but this substance was able to inhibit the effects of both dopamine and (+)-butaclamol in a concentration-dependent manner. Thus the effects of (+)-butaclamol on forskolin-stimulated cyclic AMP accumulation are mediated directly via the D2 receptor rather than by reversal of the effects of an endogenous agonist. 6. These data suggest that the D2 dopamine receptor antagonists tested here, many of which are used clinically as antipsychotic drugs, are in fact inverse agonists at human D2 dopamine receptors.

  19. Cocaine supersensitivity and enhanced motivation for reward in mice lacking dopamine D2 autoreceptors

    PubMed Central

    Bello, Estefanía P; Mateo, Yolanda; Gelman, Diego M; Noaín, Daniela; Shin, Jung H; Low, Malcolm J; Alvarez, Verónica A; Lovinger, David M; Rubinstein, Marcelo

    2011-01-01

    Dopamine (DA) D2 receptors expressed in DA neurons (D2 autoreceptors) exert a negative feedback regulation that reduces DA neuron firing, DA synthesis and DA release. As D2 receptors are mostly expressed in postsynaptic neurons, pharmacological and genetic approaches have been unable to definitively address the in vivo contribution of D2 autoreceptors to DA-mediated behaviors. We found that midbrain DA neurons from mice deficient in D2 autoreceptors (Drd2loxP/loxP; Dat+/IRES-cre, referred to as autoDrd2KO mice) lacked DA-mediated somatodendritic synaptic responses and inhibition of DA release. AutoDrd2KO mice displayed elevated DA synthesis and release, hyperlocomotion and supersensitivity to the psychomotor effects of cocaine. The mice also exhibited increased place preference for cocaine and enhanced motivation for food reward. Our results highlight the importance of D2 autoreceptors in the regulation of DA neurotransmission and demonstrate that D2 autoreceptors are important for normal motor function, food-seeking behavior, and sensitivity to the locomotor and rewarding properties of cocaine. PMID:21743470

  20. Dopamine D2/3 receptor antagonism reduces activity-based anorexia

    PubMed Central

    Klenotich, S J; Ho, E V; McMurray, M S; Server, C H; Dulawa, S C

    2015-01-01

    Anorexia nervosa (AN) is an eating disorder characterized by severe hypophagia and weight loss, and an intense fear of weight gain. Activity-based anorexia (ABA) refers to the weight loss, hypophagia and paradoxical hyperactivity that develops in rodents exposed to running wheels and restricted food access, and provides a model for aspects of AN. The atypical antipsychotic olanzapine was recently shown to reduce both AN symptoms and ABA. We examined which component of the complex pharmacological profile of olanzapine reduces ABA. Mice received 5-HT2A/2C, 5-HT3, dopamine D1-like, D2, D3 or D2/3 antagonist treatment, and were assessed for food intake, body weight, wheel running and survival in ABA. D2/3 receptor antagonists eticlopride and amisulpride reduced weight loss and hypophagia, and increased survival during ABA. Furthermore, amisulpride produced larger reductions in weight loss and hypophagia than olanzapine. Treatment with either D3 receptor antagonist SB277011A or D2 receptor antagonist L-741,626 also increased survival. All the other treatments either had no effect or worsened ABA. Overall, selective antagonism of D2 and/or D3 receptors robustly reduces ABA. Studies investigating the mechanisms by which D2 and/or D3 receptors regulate ABA, and the efficacy for D2/3 and/or D3 antagonists to treat AN, are warranted. PMID:26241351

  1. Dopamine D2 receptor expression in the corticotroph cells of the human normal pituitary gland.

    PubMed

    Pivonello, Rosario; Waaijers, Marlijn; Kros, Johan M; Pivonello, Claudia; de Angelis, Cristina; Cozzolino, Alessia; Colao, Annamaria; Lamberts, Steven W J; Hofland, Leo J

    2016-10-13

    The dopamine D2 receptor is the main dopamine receptor expressed in the human normal pituitary gland. The aim of the current study was to evaluate dopamine D2 receptor expression in the corticotroph cell populations of the anterior lobe and pars intermedia, as well as posterior lobe of the human normal pituitary gland by immunohistochemistry. Human normal pituitary gland samples obtained from routine autopsies were used for the study. In all cases, histology together with immunostaining for adrenocorticotropic hormone, melanocyte-stimulating hormone, prolactin, and neurofilaments were performed and compared to the immunostaining for D2 receptor. D2 receptor was heterogeneously expressed in the majority of the cell populations of the anterior and posterior lobe as well as in the area localized between the anterior and posterior lobe, and arbitrary defined as "intermediate zone". This zone, characterized by the presence of nerve fibers included the residual pars intermedia represented by the colloid-filled cysts lined by the remnant melanotroph cells strongly expressing D2 receptors, and clusters of corticotroph cells, belonging to the anterior lobe but localized within the cysts and adjacent to the posterior lobe, variably expressing D2 receptors. D2 dopamine receptor is expressed in the majority of the cell populations of the human normal pituitary gland, and particularly, in the different corticotroph cell populations localized in the anterior lobe and the intermediate zone of the pituitary gland.

  2. Activation of phosphoinositide 3-kinase by D2 receptor prevents apoptosis in dopaminergic cell lines.

    PubMed

    Nair, Venugopalan D; Olanow, C Warren; Sealfon, Stuart C

    2003-07-01

    Whereas dopamine agonists are known to provide symptomatic benefits for Parkinson's disease, recent clinical trials suggest that they might also be neuroprotective. Laboratory studies demonstrate that dopamine agonists can provide neuroprotective effects in a number of model systems, but the role of receptor-mediated signalling in these effects is controversial. We find that dopamine agonists have robust, concentration-dependent anti-apoptotic activity in PC12 cells that stably express human D(2L) receptors from cell death due to H(2)O(2) or trophic withdrawal and that the protective effects are abolished in the presence of D(2)-receptor antagonists. D(2) agonists are also neuroprotective in the nigral dopamine cell line SN4741, which express endogenous D(2) receptors, whereas no anti-apoptotic activity is observed in native PC12 cells, which do not express detectable D(2) receptors. Notably, the agonists studied differ in their relative efficacy to mediate anti-apoptotic effects and in their capacity to stimulate [(35)S]guanosine 5'-[gamma-thio]triphosphate ([(35)S]GTP[S]) binding, an indicator of G-protein activation. Studies with inhibitors of phosphoinositide 3-kinase (PI 3-kinase), extracellular-signal-regulated kinase or p38 mitogen-activated protein kinase indicate that the PI 3-kinase pathway is required for D(2) receptor-mediated cell survival. These studies indicate that certain dopamine agonists can complex with D(2) receptors to preferentially transactivate neuroprotective signalling pathways and to mediate increased cell survival.

  3. Reducing Ventral Tegmental Dopamine D2 Receptor Expression Selectively Boosts Incentive Motivation.

    PubMed

    de Jong, Johannes W; Roelofs, Theresia J M; Mol, Frédérique M U; Hillen, Anne E J; Meijboom, Katharina E; Luijendijk, Mieneke C M; van der Eerden, Harrie A M; Garner, Keith M; Vanderschuren, Louk J M J; Adan, Roger A H

    2015-08-01

    Altered mesolimbic dopamine signaling has been widely implicated in addictive behavior. For the most part, this work has focused on dopamine within the striatum, but there is emerging evidence for a role of the auto-inhibitory, somatodendritic dopamine D2 receptor (D2R) in the ventral tegmental area (VTA) in addiction. Thus, decreased midbrain D2R expression has been implicated in addiction in humans. Moreover, knockout of the gene encoding the D2R receptor (Drd2) in dopamine neurons has been shown to enhance the locomotor response to cocaine in mice. Therefore, we here tested the hypothesis that decreasing D2R expression in the VTA of adult rats, using shRNA knockdown, promotes addiction-like behavior in rats responding for cocaine or palatable food. Rats with decreased VTA D2R expression showed markedly increased motivation for both sucrose and cocaine under a progressive ratio schedule of reinforcement, but the acquisition or maintenance of cocaine self-administration were not affected. They also displayed enhanced cocaine-induced locomotor activity, but no change in basal locomotion. This robust increase in incentive motivation was behaviorally specific, as we did not observe any differences in fixed ratio responding, extinction responding, reinstatement or conditioned suppression of cocaine, and sucrose seeking. We conclude that VTA D2R knockdown results in increased incentive motivation, but does not directly promote other aspects of addiction-like behavior.

  4. Agonist signalling properties of radiotracers used for imaging of dopamine D2/3 receptors

    PubMed Central

    2014-01-01

    Background Dopamine D2/3 receptor (D2/3R) agonist radiopharmaceuticals are considered superior to antagonists to detect dopamine release, e.g. induced by amphetamines. Agonists bind preferentially to the high-affinity state of the dopamine D2R, which has been proposed as the reason why agonists are more sensitive to detect dopamine release than antagonist radiopharmaceuticals, but this theory has been challenged. Interestingly, not all agonists similarly activate the classic cyclic adenosine mono phosphate (cAMP) and the ?-arrestin-2 pathway, some stimulate preferentially one of these pathways; a phenomenon called biased agonism. Because these pathways can be affected separately by pathologies or drugs (including dopamine releasers), it is important to know how agonist radiotracers act on these pathways. Therefore, we characterized the intracellular signalling of the well-known D2/3R agonist radiopharmaceuticals NPA and PHNO and of several novel D2/3R agonists. Methods cAMP accumulation and ?-arrestin-2 recruitment were measured on cells expressing human D2R. Results All tested agonists showed (almost) full agonism in both pathways. Conclusions The tested D2/3R agonist radiopharmaceuticals did not exhibit biased agonism in vitro. Consequently, it is likely that drugs (including psychostimulants like amphetamines) and/or pathologies that influence the cAMP and/or the ?-arrestin-2 pathway may influence the binding of these radiopharmaceuticals. PMID:25977878

  5. Postsynaptic D2 dopamine receptor supersensitivity in the striatum of mice lacking TAAR1.

    PubMed

    Espinoza, Stefano; Ghisi, Valentina; Emanuele, Marco; Leo, Damiana; Sukhanov, Ilya; Sotnikova, Tatiana D; Chieregatti, Evelina; Gainetdinov, Raul R

    2015-06-01

    Trace Amine-Associated Receptor 1 (TAAR1) is a G protein-coupled receptor (GPCR) known to modulate dopaminergic system through several mechanisms. Mice lacking this receptor show a higher sensitivity to dopaminergic stimuli, such as amphetamine; however, it is not clear whether D1 or D2 dopamine receptors and which associated intracellular signaling events are involved in this modulation. In the striatum of TAAR1 knock out (TAAR1-KO mice) we found that D2, but not D1, dopamine receptors were over-expressed, both in terms of mRNA and protein levels. Moreover, the D2 dopamine receptor-related G protein-independent AKT/GSK3 signaling pathway was selectively activated, as indicated by the decrease of phosphorylation of AKT and GSK3β. The decrease in phospho-AKT levels, suggesting an increase in D2 dopamine receptor activity in basal conditions, was associated with an increase of AKT/PP2A complex, as revealed by co-immunoprecipitation experiments. Finally, we found that the locomotor activation induced by the D2 dopamine receptor agonist quinpirole, but not by the full D1 dopamine receptor agonist SKF-82958, was increased in TAAR1-KO mice. These data demonstrate pronounced supersensitivity of postsynaptic D2 dopamine receptors in the striatum of TAAR1-KO mice and indicate that a close interaction of TAAR1 and D2 dopamine receptors at the level of postsynaptic structures has important functional consequences.

  6. Cannabidiol is a partial agonist at dopamine D2High receptors, predicting its antipsychotic clinical dose

    PubMed Central

    Seeman, P

    2016-01-01

    Although all current antipsychotics act by interfering with the action of dopamine at dopamine D2 receptors, two recent reports showed that 800 to 1000 mg of cannabidiol per day alleviated the signs and symptoms of schizophrenia, although cannabidiol is not known to act on dopamine receptors. Because these recent clinical findings may indicate an important exception to the general rule that all antipsychotics interfere with dopamine at dopamine D2 receptors, the present study examined whether cannabidiol acted directly on D2 receptors, using tritiated domperidone to label rat brain striatal D2 receptors. It was found that cannabidiol inhibited the binding of radio-domperidone with dissociation constants of 11 nm at dopamine D2High receptors and 2800 nm at dopamine D2Low receptors, in the same biphasic manner as a dopamine partial agonist antipsychotic drug such as aripiprazole. The clinical doses of cannabidiol are sufficient to occupy the functional D2High sites. it is concluded that the dopamine partial agonist action of cannabidiol may account for its clinical antipsychotic effects. PMID:27754480

  7. Dopamine D2-receptor blockade enhances decoding of prefrontal signals in humans.

    PubMed

    Kahnt, Thorsten; Weber, Susanna C; Haker, Helene; Robbins, Trevor W; Tobler, Philippe N

    2015-03-04

    The prefrontal cortex houses representations critical for ongoing and future behavior expressed in the form of patterns of neural activity. Dopamine has long been suggested to play a key role in the integrity of such representations, with D2-receptor activation rendering them flexible but weak. However, it is currently unknown whether and how D2-receptor activation affects prefrontal representations in humans. In the current study, we use dopamine receptor-specific pharmacology and multivoxel pattern-based functional magnetic resonance imaging to test the hypothesis that blocking D2-receptor activation enhances prefrontal representations. Human subjects performed a simple reward prediction task after double-blind and placebo controlled administration of the D2-receptor antagonist amisulpride. Using a whole-brain searchlight decoding approach we show that D2-receptor blockade enhances decoding of reward signals in the medial orbitofrontal cortex. Examination of activity patterns suggests that amisulpride increases the separation of activity patterns related to reward versus no reward. Moreover, consistent with the cortical distribution of D2 receptors, post hoc analyses showed enhanced decoding of motor signals in motor cortex, but not of visual signals in visual cortex. These results suggest that D2-receptor blockade enhances content-specific representations in frontal cortex, presumably by a dopamine-mediated increase in pattern separation. These findings are in line with a dual-state model of prefrontal dopamine, and provide new insights into the potential mechanism of action of dopaminergic drugs.

  8. Withdrawal from continuous or intermittent cocaine administration: changes in D2 receptor function.

    PubMed

    King, G R; Ellinwood, E H; Silvia, C; Joyner, C M; Xue, Z; Caron, M G; Lee, T H

    1994-05-01

    Intermittent cocaine administration produces sensitization, whereas the continuous administration of cocaine produces tolerance to the effects of subsequent cocaine administration during withdrawal. The present study examined whether the effects of these two dosing regimens are related to alterations in the functional status of dopamine (DA) D2 receptors. In all experiments, rats were withdrawn for 7 days from a 14-day pretreatment regimen involving either continuous or intermittent cocaine administration. Experiments examined changes in the behavioral response to an autoreceptor-selective dose of apomorphine, the effects of sulpiride on electrically stimulated DA release in striatal brain slices and striatal D2 receptor binding, and mRNA levels. The results indicate that the continuous administration of cocaine produces findings consistent with D2 autoreceptor supersensitivity; there was enhanced inhibition of behavior after the autoreceptor-selective dose of apomorphine, decreased electrically stimulated DA release in the absence of sulpiride, and enhanced electrically stimulated DA release in the presence of sulpiride. However, there were no changes in postsynaptic D2 receptor binding or mRNA levels. Intermittent cocaine administration did not produce evidence of D2 autoreceptor subsensitivity: there was no decrease in inhibition of behavior after the autoreceptor-selective dose of apomorphine, no changes in electrically stimulated DA release in the absence or presence of D2 receptor blockade, and no change in the levels of D2 receptor binding; however, D2 mRNA levels were decreased by 22%. Overall, the present results are consistent with the hypothesis that the expression of tolerance induced by continuous cocaine administration is associated with D2 autoreceptor supersensitivity.

  9. Quantitative Imaging of D-2-Hydroxyglutarate in Selected Histological Tissue Areas by a Novel Bioluminescence Technique.

    PubMed

    Voelxen, Nadine F; Walenta, Stefan; Proescholdt, Martin; Dettmer, Katja; Pusch, Stefan; Mueller-Klieser, Wolfgang

    2016-01-01

    Patients with malignant gliomas have a poor prognosis with average survival of less than 1 year. Whereas in other tumor entities the characteristics of tumor metabolism are successfully used for therapeutic approaches, such developments are very rare in brain tumors, notably in gliomas. One metabolic feature characteristic of gliomas, in particular diffuse astrocytomas and oligodendroglial tumors, is the variable content of D-2-hydroxyglutarate (D2HG), a metabolite that was discovered first in this tumor entity. D2HG is generated in large amounts due to various "gain-of-function" mutations in the isocitrate dehydrogenases IDH1 and IDH2. Meanwhile, D2HG has been detected in several other tumor entities, including intrahepatic bile-duct cancer, chondrosarcoma, acute myeloid leukemia, and angioimmunoblastic T-cell lymphoma. D2HG is barely detectable in healthy tissue (<0.1 mM), but its concentration increases up to 35 mM in malignant tumor tissues. Consequently, the "oncometabolite" D2HG has gained increasing interest in the field of tumor metabolism. To facilitate its quantitative measurement without loss of spatial resolution at a microscopical level, we have developed a novel bioluminescence assay for determining D2HG in sections of snap-frozen tissue. The assay was verified independently by photometric tests and liquid chromatography/mass spectrometry. The novel technique allows the microscopically resolved determination of D2HG in a concentration range of 0-10 μmol/g tissue (wet weight). In combination with the already established bioluminescence imaging techniques for ATP, glucose, pyruvate, and lactate, the novel D2HG assay enables a comparative characterization of the metabolic profile of individual tumors in a further dimension.

  10. 3D-2D ultrasound feature-based registration for navigated prostate biopsy: a feasibility study.

    PubMed

    Selmi, Sonia Y; Promayon, Emmanuel; Troccaz, Jocelyne

    2016-08-01

    The aim of this paper is to describe a 3D-2D ultrasound feature-based registration method for navigated prostate biopsy and its first results obtained on patient data. A system combining a low-cost tracking system and a 3D-2D registration algorithm was designed. The proposed 3D-2D registration method combines geometric and image-based distances. After extracting features from ultrasound images, 3D and 2D features within a defined distance are matched using an intensity-based function. The results are encouraging and show acceptable errors with simulated transforms applied on ultrasound volumes from real patients.

  11. TCTEX1D2 mutations underlie Jeune asphyxiating thoracic dystrophy with impaired retrograde intraflagellar transport

    PubMed Central

    Schmidts, Miriam; Hou, Yuqing; Cortés, Claudio R.; Mans, Dorus A.; Huber, Celine; Boldt, Karsten; Patel, Mitali; van Reeuwijk, Jeroen; Plaza, Jean-Marc; van Beersum, Sylvia E. C.; Yap, Zhi Min; Letteboer, Stef J. F.; Taylor, S. Paige; Herridge, Warren; Johnson, Colin A.; Scambler, Peter J.; Ueffing, Marius; Kayserili, Hulya; Krakow, Deborah; King, Stephen M.; Beales, Philip L.; Al-Gazali, Lihadh; Wicking, Carol; Cormier-Daire, Valerie; Roepman, Ronald; Mitchison, Hannah M.; Witman, George B.; Al-Turki, Saeed; Anderson, Carl; Anney, Richard; Antony, Dinu; Asimit, Jennifer; Ayub, Mohammad; Barrett, Jeff; Barroso, Inês; Bentham, Jamie; Bhattacharya, Shoumo; Blackwood, Douglas; Bobrow, Martin; Bochukova, Elena; Bolton, Patrick; Boustred, Chris; Breen, Gerome; Brion, Marie-Jo; Brown, Andrew; Calissano, Mattia; Carss, Keren; Chatterjee, Krishna; Chen, Lu; Cirak, Sebhattin; Clapham, Peter; Clement, Gail; Coates, Guy; Collier, David; Cosgrove, Catherine; Cox, Tony; Craddock, Nick; Crooks, Lucy; Curran, Sarah; Daly, Allan; Danecek, Petr; Smith, George Davey; Day-Williams, Aaron; Day, Ian; Durbin, Richard; Edkins, Sarah; Ellis, Peter; Evans, David; Farooqi, I. Sadaf; Fatemifar, Ghazaleh; Fitzpatrick, David; Flicek, Paul; Floyd, Jamie; Foley, A. Reghan; Franklin, Chris; Futema, Marta; Gallagher, Louise; Gaunt, Tom; Geschwind, Daniel; Greenwood, Celia; Grozeva, Detelina; Guo, Xiaosen; Gurling, Hugh; Hart, Deborah; Hendricks, Audrey; Holmans, Peter; Huang, Jie; Humphries, Steve E.; Hurles, Matt; Hysi, Pirro; Jackson, David; Jamshidi, Yalda; Jewell, David; Chris, Joyce; Kaye, Jane; Keane, Thomas; Kemp, John; Kennedy, Karen; Kent, Alastair; Kolb-Kokocinski, Anja; Lachance, Genevieve; Langford, Cordelia; Lee, Irene; Li, Rui; Li, Yingrui; Ryan, Liu; Lönnqvist, Jouko; Lopes, Margarida; MacArthur, Daniel G.; Massimo, Mangino; Marchini, Jonathan; Maslen, John; McCarthy, Shane; McGuffin, Peter; McIntosh, Andrew; McKechanie, Andrew; McQuillin, Andrew; Memari, Yasin; Metrustry, Sarah; Min, Josine; Moayyeri, Alireza; Morris, James; Muddyman, Dawn; Muntoni, Francesco; Northstone, Kate; O'Donovan, Michael; O'Rahilly, Stephen; Onoufriadis, Alexandros; Oualkacha, Karim; Owen, Michael; Palotie, Aarno; Panoutsopoulou, Kalliope; Parker, Victoria; Parr, Jeremy; Paternoster, Lavinia; Paunio, Tiina; Payne, Felicity; Perry, John; Pietilainen, Olli; Plagnol, Vincent; Quail, Michael A.; Quaye, Lydia; Raymond, Lucy; Rehnström, Karola; Brent Richards, J.; Ring, Sue; Ritchie, Graham R S; Savage, David B.; Schoenmakers, Nadia; Semple, Robert K.; Serra, Eva; Shihab, Hashem; Shin, So-Youn; Skuse, David; Small, Kerrin; Smee, Carol; Soler, Artigas María; Soranzo, Nicole; Southam, Lorraine; Spector, Tim; St Pourcain, Beate; St. Clair, David; Stalker, Jim; Surdulescu, Gabriela; Suvisaari, Jaana; Tachmazidou, Ioanna; Tian, Jing; Timpson, Nic; Tobin, Martin; Valdes, Ana; van Kogelenberg, Margriet; Vijayarangakannan, Parthiban; Wain, Louise; Walter, Klaudia; Wang, Jun; Ward, Kirsten; Wheeler, Ellie; Whittall, Ros; Williams, Hywel; Williamson, Kathy; Wilson, Scott G.; Wong, Kim; Whyte, Tamieka; ChangJiang, Xu; Zeggini, Eleftheria; Zhang, Feng; Zheng, Hou-Feng

    2015-01-01

    The analysis of individuals with ciliary chondrodysplasias can shed light on sensitive mechanisms controlling ciliogenesis and cell signalling that are essential to embryonic development and survival. Here we identify TCTEX1D2 mutations causing Jeune asphyxiating thoracic dystrophy with partially penetrant inheritance. Loss of TCTEX1D2 impairs retrograde intraflagellar transport (IFT) in humans and the protist Chlamydomonas, accompanied by destabilization of the retrograde IFT dynein motor. We thus define TCTEX1D2 as an integral component of the evolutionarily conserved retrograde IFT machinery. In complex with several IFT dynein light chains, it is required for correct vertebrate skeletal formation but may be functionally redundant under certain conditions. PMID:26044572

  12. D5 dopamine receptor carboxyl tail involved in D5-D2 heteromer formation

    PubMed Central

    O’Dowd, Brian F.; Nguyen, Tuan; Ji, Xiaodong; George, Susan R.

    2013-01-01

    We have demonstrated that D5 and D2 dopamine receptors exist as heteromers in cells, and determined these receptor interact through amino acids in the cytoplasmic regions of each receptor. Specifically involved in heteromer formation we identified in the carboxyl tail of the D5 receptor three adjacent glutamic acid residues, and in intracellular loop 3 of the D2 receptor two adjacent arginine residues. Any pairing of these three D5 receptor glutamic acids were sufficient for heteromer formation. These identified residues in D5 and D2 receptors are oppositely charged and likely interact by electrostatic interactions. PMID:23318175

  13. Chronic social defeat stress increases dopamine D2 receptor dimerization in the prefrontal cortex of adult mice.

    PubMed

    Bagalkot, T R; Jin, H-M; Prabhu, V V; Muna, S S; Cui, Y; Yadav, B K; Chae, H-J; Chung, Y-C

    2015-12-17

    The present study aimed to examine the effects of chronic social defeat stress on the dopamine receptors and proteins involved in post-endocytic trafficking pathways. Adult mice were divided into susceptible and unsusceptible groups after 10 days of social defeat stress. Western blot analysis was used to measure the protein expression levels of dopamine D2 receptors (D2Rs), a short (D2S) and a long form (D2L) and, D2R monomers and dimers, dopamine D1 receptors (D1Rs), neuronal calcium sensor-1 (NCS-1) and G protein-coupled receptor-associated sorting protein-1 (GASP-1), and reverse transcription-polymerase chain reaction (RT-PCR) was used to measure the mRNA expression levels of D2S, D2L, D2R monomers and dimers, and D1Rs in different brain areas. We observed increased expression of D2S, D2L and D2Rs dimers in the prefrontal cortex (PFC) of susceptible and/or unsusceptible mice compared with controls. The only significant findings with regard to mRNA expression levels were lower expression of D2S mRNA in the amygdala (AMYG) of susceptible and unsusceptible mice compared with controls. The present study demonstrated that chronic social defeat stress induced increased expression of D2S, D2L, and D2R dimers in the PFC of susceptible and/or unsusceptible mice.

  14. D2 to D2

    NASA Astrophysics Data System (ADS)

    Ezhuthachan, Bobby; Mukhi, Sunil; Papageorgakis, Constantinos

    2008-07-01

    Starting from maximally supersymmetric (2+1)d Yang-Mills theory and using a duality transformation due to de Wit, Nicolai and Samtleben, we obtain the ghost-free Lorentzian 3-algebra theory that has recently been proposed to describe M2-branes. Our derivation does not invoke any properties of 3-algebras. Being derivable from SYM, the final theory is manifestly equivalent to it on-shell and should not be thought of as the IR limit that describes M2-branes, though it does have enhanced R-symmetry as well as superconformal symmetry off-shell.

  15. Near infrared second overtone cw-cavity ringdown spectroscopy of D2H+ ions

    NASA Astrophysics Data System (ADS)

    Hlavenka, P.; Plasil, R.; Bano, G.; Korolov, I.; Gerlich, D.; Ramanlal, J.; Tennyson, J.; Glosik, J.

    2006-09-01

    A study of D2H+ ions in their lowest rotational states is presented. The ions are generated in pulsed discharge in liquid N2 cooled He/Ar/H2/D2 gas mixture. Near infrared (NIR) second overtone transitions in the 6534-6536 cm-1 (1.529-1.530 [mu]m) region are used to identify the ions and determine their degree of rotational excitation. The data were obtained using NIR cavity ringdown absorption spectroscopy (NIR-CRDS). The sensitivity obtained was typically 5 x 10-9 cm-1. The measured second overtone transition frequencies are in very good agreement (better than 0.02 cm-1) with ab initio predictions. From the Doppler broadening the kinetic temperature of ions is estimated to be (220 +/- 50) K. The absolute number density of D2H+ as a function of H2/D2 mixing ratio and time is measured.

  16. STS-55 Columbia, Orbiter Vehicle (OV) 102, payload bay with SL-D2 module

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Spacelab Deutsche 2 (SL-D2) science module and spacelab (SL) long tunnel is documented in the payload bay (PLB) of the Earth-orbiting Columbia, Orbiter Vehicle (OV) 102. The support struts and handrails on the SL joggle section are visible in the foreground with the SL-D2 flex section and interface behind it. On the SL-D2 module foward end cone applied to the thermal blanket cover are the insignias of the European Space Agency (ESA) (left) and the SL-D2 payload. In the background are OV-102's vertical tail and the two orbital maneuvering system (OMS) pods backdropped against the cloud-covered Earth surface and the blackness of space.

  17. Production of the excited charm mesons D1 and D2* at HERA

    NASA Astrophysics Data System (ADS)

    Abramowicz, H.; Abt, I.; Adamczyk, L.; Adamus, M.; Aggarwal, R.; Antonelli, S.; Antonioli, P.; Antonov, A.; Arneodo, M.; Arslan, O.; Aushev, V.; Aushev, Y.; Bachynska, O.; Bamberger, A.; Barakbaev, A. N.; Barbagli, G.; Bari, G.; Barreiro, F.; Bartosik, N.; Bartsch, D.; Basile, M.; Behnke, O.; Behr, J.; Behrens, U.; Bellagamba, L.; Bertolin, A.; Bhadra, S.; Bindi, M.; Blohm, C.; Bokhonov, V.; Bołd, T.; Bondarenko, K.; Boos, E. G.; Borras, K.; Boscherini, D.; Bot, D.; Brock, I.; Brownson, E.; Brugnera, R.; Brümmer, N.; Bruni, A.; Bruni, G.; Brzozowska, B.; Bussey, P. J.; Bylsma, B.; Caldwell, A.; Capua, M.; Carlin, R.; Catterall, C. D.; Chekanov, S.; Chwastowski, J.; Ciborowski, J.; Ciesielski, R.; Cifarelli, L.; Cindolo, F.; Contin, A.; Cooper-Sarkar, A. M.; Coppola, N.; Corradi, M.; Corriveau, F.; Costa, M.; D'Agostini, G.; Dal Corso, F.; del Peso, J.; Dementiev, R. K.; De Pasquale, S.; Derrick, M.; Devenish, R. C. E.; Dobur, D.; Dolgoshein, B. A.; Dolinska, G.; Doyle, A. T.; Drugakov, V.; Durkin, L. S.; Dusini, S.; Eisenberg, Y.; Ermolov, P. F.; Eskreys, A.; Fang, S.; Fazio, S.; Ferrando, J.; Ferrero, M. I.; Figiel, J.; Foster, B.; Gach, G.; Galas, A.; Gallo, E.; Garfagnini, A.; Geiser, A.; Gialas, I.; Gizhko, A.; Gladilin, L. K.; Gladkov, D.; Glasman, C.; Gogota, O.; Golubkov, Yu. A.; Göttlicher, P.; Grabowska-Bołd, I.; Grebenyuk, J.; Gregor, I.; Grigorescu, G.; Grzelak, G.; Gueta, O.; Guzik, M.; Gwenlan, C.; Haas, T.; Hain, W.; Hamatsu, R.; Hart, J. C.; Hartmann, H.; Hartner, G.; Hilger, E.; Hochman, D.; Hori, R.; Hüttmann, A.; Ibrahim, Z. A.; Iga, Y.; Ingbir, R.; Ishitsuka, M.; Jakob, H.-P.; Januschek, F.; Jones, T. W.; Jüngst, M.; Kadenko, I.; Kahle, B.; Kananov, S.; Kanno, T.; Karshon, U.; Karstens, F.; Katkov, I. I.; Kaur, M.; Kaur, P.; Keramidas, A.; Khein, L. A.; Kim, J. Y.; Kisielewska, D.; Kitamura, S.; Klanner, R.; Klein, U.; Koffeman, E.; Kondrashova, N.; Kononenko, O.; Kooijman, P.; Korol, Ie.; Korzhavina, I. A.; Kotański, A.; Kötz, U.; Kowalski, H.; Kuprash, O.; Kuze, M.; Lee, A.; Levchenko, B. B.; Levy, A.; Libov, V.; Limentani, S.; Ling, T. Y.; Lobodzinska, E.; Lohmann, W.; Löhr, B.; Lohrmann, E.; Long, K. R.; Longhin, A.; Lontkovskyi, D.; Lukina, O. Yu.; Maeda, J.; Magill, S.; Makarenko, I.; Malka, J.; Mankel, R.; Margotti, A.; Marini, G.; Martin, J. F.; Mastroberardino, A.; Mattingly, M. C. K.; Melzer-Pellmann, I.-A.; Mergelmeyer, S.; Miglioranzi, S.; Mohamad Idris, F.; Monaco, V.; Montanari, A.; Morris, J. D.; Mujkic, K.; Musgrave, B.; Nagano, K.; Namsoo, T.; Nania, R.; Nigro, A.; Ning, Y.; Nobe, T.; Notz, D.; Nowak, R. J.; Nuncio-Quiroz, A. E.; Oh, B. Y.; Okazaki, N.; Olkiewicz, K.; Onishchuk, Yu.; Papageorgiu, K.; Parenti, A.; Paul, E.; Pawlak, J. M.; Pawlik, B.; Pelfer, P. G.; Pellegrino, A.; Perlański, W.; Perrey, H.; Piotrzkowski, K.; Pluciński, P.; Pokrovskiy, N. S.; Polini, A.; Proskuryakov, A. S.; Przybycień, M.; Raval, A.; Reeder, D. D.; Reisert, B.; Ren, Z.; Repond, J.; Ri, Y. D.; Robertson, A.; Roloff, P.; Rubinsky, I.; Ruspa, M.; Sacchi, R.; Samson, U.; Sartorelli, G.; Savin, A. A.; Saxon, D. H.; Schioppa, M.; Schlenstedt, S.; Schleper, P.; Schmidke, W. B.; Schneekloth, U.; Schönberg, V.; Schörner-Sadenius, T.; Schwartz, J.; Sciulli, F.; Shcheglova, L. M.; Shehzadi, R.; Shimizu, S.; Singh, I.; Skillicorn, I. O.; Słomiński, W.; Smith, W. H.; Sola, V.; Solano, A.; Son, D.; Sosnovtsev, V.; Spiridonov, A.; Stadie, H.; Stanco, L.; Stefaniuk, N.; Stern, A.; Stewart, T. P.; Stifutkin, A.; Stopa, P.; Suchkov, S.; Susinno, G.; Suszycki, L.; Sztuk-Dambietz, J.; Szuba, D.; Szuba, J.; Tapper, A. D.; Tassi, E.; Terrón, J.; Theedt, T.; Tiecke, H.; Tokushuku, K.; Tomaszewska, J.; Trusov, V.; Tsurugai, T.; Turcato, M.; Turkot, O.; Tymieniecka, T.; Vázquez, M.; Verbytskyi, A.; Viazlo, O.; Vlasov, N. N.; Walczak, R.; Wan Abdullah, W. A. T.; Whitmore, J. J.; Wichmann, K.; Wiggers, L.; Wing, M.; Wlasenko, M.; Wolf, G.; Wolfe, H.; Wrona, K.; Yagües-Molina, A. G.; Yamada, S.; Yamazaki, Y.; Yoshida, R.; Youngman, C.; Zabiegalov, O.; Żarnecki, A. F.; Zawiejski, L.; Zenaiev, O.; Zeuner, W.; Zhautykov, B. O.; Zhmak, N.; Zichichi, A.; Zolkapli, Z.; Zotkin, D. S.; ZEUS Collaboration

    2013-01-01

    The production of the excited charm mesons D1(2420) and D2*(2460) in ep collisions has been measured with the ZEUS detector at HERA using an integrated luminosity of 373 pb. The masses of the neutral and charged states, the widths of the neutral states, and the helicity parameter of D1(2420 were determined and compared with other measurements and with theoretical expectations. The measured helicity parameter of the D10 allows for some mixing of S- and D-waves in its decay to Dπ∓. The result is also consistent with a pure D-wave decay. Ratios of branching fractions of the two decay modes of the D2*(2460 and D2*(2460 states were measured and compared with previous measurements. The fractions of charm quarks hadronising into D1 and D2* were measured and are consistent with those obtained in e+e- annihilations.

  18. Myocardial accumulation of a dopamine D2 receptor-binding radioligand, 2'-iodospiperone.

    PubMed

    Saji, H; Yonekura, Y; Tanahashi, K; Iida, Y; Iwasaki, Y; Magata, Y; Konishi, J; Yokoyama, A

    1993-08-01

    125I-2'-iodospiperone (2'-ISP), which has a high and selective affinity for dopamine D2 receptors, produced a high myocardial accumulation of radioactivity in the early phase after intravenous injection into mice. A human scintigraphic study also showed that the myocardium was clearly visualized soon after intravenous injection of the tracer. Analysis of the myocardial homogenate obtained from mice showed that 125I-2'-ISP was metabolically stable and was taken up the myocardium in its intact form. Administration of spiperone significantly reduced the myocardial uptake of 125I-2'-ISP in mice. Treatment with haloperidol and (+) butaclamol, which have a high affinity for dopamine D2 receptors, also tended to reduce the myocardial uptake of radioactivity, while (-)-butaclamol, which has no affinity for dopamine D2 receptors, caused no change in uptake. These findings suggest that the myocardial accumulation of 2'-ISP occurred in association with dopamine D2 (DA2) receptors.

  19. Vitamin D2 Supplementation Amplifies Eccentric Exercise-Induced Muscle Damage in NASCAR Pit Crew Athletes

    PubMed Central

    Nieman, David C.; Gillitt, Nicholas D.; Shanely, R. Andrew; Dew, Dustin; Meaney, Mary Pat; Luo, Beibei

    2013-01-01

    This study determined if 6-weeks vitamin D2 supplementation (vitD2, 3800 IU/day) had an influence on muscle function, eccentric exercise-induced muscle damage (EIMD), and delayed onset of muscle soreness (DOMS) in National Association for Stock Car Auto Racing (NASCAR) NASCAR pit crew athletes. Subjects were randomized to vitD2 (n = 13) and placebo (n = 15), and ingested supplements (double-blind) for six weeks. Blood samples were collected and muscle function tests conducted pre- and post-study (leg-back and hand grip dynamometer strength tests, body weight bench press to exhaustion, vertical jump, 30-s Wingate test). Post-study, subjects engaged in 90 min eccentric-based exercise, with blood samples and DOMS ratings obtained immediately after and 1- and 2-days post-exercise. Six weeks vitD2 increased serum 25(OH)D2 456% and decreased 25(OH)D3 21% versus placebo (p < 0.001, p = 0.036, respectively), with no influence on muscle function test scores. The post-study eccentric exercise bout induced EIMD and DOMS, with higher muscle damage biomarkers measured in vitD2 compared to placebo (myoglobin 252%, 122% increase, respectively, p = 0.001; creatine phosphokinase 24 h post-exercise, 169%, 32%, p < 0.001), with no differences for DOMS. In summary, 6-weeks vitD2 (3800 IU/day) significantly increased 25(OH)D2 and decreased 25(OH)D3, had no effect on muscle function tests, and amplified muscle damage markers in NASCAR pit crew athletes following eccentric exercise. PMID:24362707

  20. Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain

    DOE PAGES

    Volkow, N. D.; Wang, G. -J.; Logan, J.; ...

    2015-04-14

    Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A2A receptors (A2AR). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [11C]raclopride (DA D2/D3 receptor radioligand sensitive to endogenous DA) to assess if caffeine increased DA release inmore » striatum in 20 healthy controls. Caffeine (300mg p.o.) significantly increased the availability of D2/D3 receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D2/D3 receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D2/D3 receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D2/D3 receptor availability. Instead, we interpret our findings to reflect an increase in D2/D3 receptor levels in striatum with caffeine (or changes in affinity). Furthermore, the association between increases in D2/D3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D2/D3 receptors.« less

  1. Vitamin D2 supplementation amplifies eccentric exercise-induced muscle damage in NASCAR pit crew athletes.

    PubMed

    Nieman, David C; Gillitt, Nicholas D; Shanely, R Andrew; Dew, Dustin; Meaney, Mary Pat; Luo, Beibei

    2013-12-20

    This study determined if 6-weeks vitamin D2 supplementation (vitD2, 3800 IU/day) had an influence on muscle function, eccentric exercise-induced muscle damage (EIMD), and delayed onset of muscle soreness (DOMS) in National Association for Stock Car Auto Racing (NASCAR) NASCAR pit crew athletes. Subjects were randomized to vitD2 (n=13) and placebo (n=15), and ingested supplements (double-blind) for six weeks. Blood samples were collected and muscle function tests conducted pre- and post-study (leg-back and hand grip dynamometer strength tests, body weight bench press to exhaustion, vertical jump, 30-s Wingate test). Post-study, subjects engaged in 90 min eccentric-based exercise, with blood samples and DOMS ratings obtained immediately after and 1- and 2-days post-exercise. Six weeks vitD2 increased serum 25(OH)D2 456% and decreased 25(OH)D3 21% versus placebo (p<0.001, p=0.036, respectively), with no influence on muscle function test scores. The post-study eccentric exercise bout induced EIMD and DOMS, with higher muscle damage biomarkers measured in vitD2 compared to placebo (myoglobin 252%, 122% increase, respectively, p=0.001; creatine phosphokinase 24 h post-exercise, 169%, 32%, p<0.001), with no differences for DOMS. In summary, 6-weeks vitD2 (3800 IU/day) significantly increased 25(OH)D2 and decreased 25(OH)D3, had no effect on muscle function tests, and amplified muscle damage markers in NASCAR pit crew athletes following eccentric exercise.

  2. Caffeine increases striatal dopamine D2/D3 receptor availability in the human brain.

    PubMed

    Volkow, N D; Wang, G-J; Logan, J; Alexoff, D; Fowler, J S; Thanos, P K; Wong, C; Casado, V; Ferre, S; Tomasi, D

    2015-04-14

    Caffeine, the most widely consumed psychoactive substance in the world, is used to promote wakefulness and enhance alertness. Like other wake-promoting drugs (stimulants and modafinil), caffeine enhances dopamine (DA) signaling in the brain, which it does predominantly by antagonizing adenosine A2A receptors (A2AR). However, it is unclear if caffeine, at the doses consumed by humans, increases DA release or whether it modulates the functions of postsynaptic DA receptors through its interaction with adenosine receptors, which modulate them. We used positron emission tomography and [(11)C]raclopride (DA D2/D3 receptor radioligand sensitive to endogenous DA) to assess if caffeine increased DA release in striatum in 20 healthy controls. Caffeine (300 mg p.o.) significantly increased the availability of D2/D3 receptors in putamen and ventral striatum, but not in caudate, when compared with placebo. In addition, caffeine-induced increases in D2/D3 receptor availability in the ventral striatum were associated with caffeine-induced increases in alertness. Our findings indicate that in the human brain, caffeine, at doses typically consumed, increases the availability of DA D2/D3 receptors, which indicates that caffeine does not increase DA in the striatum for this would have decreased D2/D3 receptor availability. Instead, we interpret our findings to reflect an increase in D2/D3 receptor levels in striatum with caffeine (or changes in affinity). The association between increases in D2/D3 receptor availability in ventral striatum and alertness suggests that caffeine might enhance arousal, in part, by upregulating D2/D3 receptors.

  3. Bacterial Ice Nucleation in Monodisperse D2O and H2O-in-Oil Emulsions.

    PubMed

    Weng, Lindong; Tessier, Shannon N; Smith, Kyle; Edd, Jon F; Stott, Shannon L; Toner, Mehmet

    2016-09-13

    Ice nucleation is of fundamental significance in many areas, including atmospheric science, food technology, and cryobiology. In this study, we investigated the ice-nucleation characteristics of picoliter-sized drops consisting of different D2O and H2O mixtures with and without the ice-nucleating bacteria Pseudomonas syringae. We also studied the effects of commonly used cryoprotectants such as ethylene glycol, propylene glycol, and trehalose on the nucleation characteristics of D2O and H2O mixtures. The results show that the median freezing temperature of the suspension containing 1 mg/mL of a lyophilized preparation of P. syringae is as high as -4.6 °C for 100% D2O, compared to -8.9 °C for 100% H2O. As the D2O concentration increases every 25% (v/v), the profile of the ice-nucleation kinetics of D2O + H2O mixtures containing 1 mg/mL Snomax shifts by about 1 °C, suggesting an ideal mixing behavior of D2O and H2O. Furthermore, all of the cryoprotectants investigated in this study are found to depress the freezing phenomenon. Both the homogeneous and heterogeneous freezing temperatures of these aqueous solutions depend on the water activity and are independent of the nature of the solute. These findings enrich our fundamental knowledge of D2O-related ice nucleation and suggest that the combination of D2O and ice-nucleating agents could be a potential self-ice-nucleating formulation. The implications of self-nucleation include a higher, precisely controlled ice seeding temperature for slow freezing that would significantly improve the viability of many ice-assisted cryopreservation protocols.

  4. Effect of supplementation with vitamin D2-enhanced mushrooms on vitamin D status in healthy adults.

    PubMed

    Stepien, Magdalena; O'Mahony, Louise; O'Sullivan, Aifric; Collier, John; Fraser, William D; Gibney, Michael J; Nugent, Anne P; Brennan, Lorraine

    2013-01-01

    Vitamin D deficiency is emerging worldwide and many studies now suggest its role in the development of several chronic diseases. Due to the low level of vitamin D naturally occurring in food there is a need for supplementation and use of vitamin D-enhanced products. The aim of the present study was to determine if daily consumption of vitamin D2-enhanced mushrooms increased vitamin D status in free-living healthy adults or affected markers of the metabolic syndrome. A total of ninety volunteers (aged 40-65 years) were randomly assigned to one of two 4-week studies: mushroom study (15 µg vitamin D2 or placebo mushroom powder) and capsule study (15 µg vitamin D3 or placebo capsules). Consumption of vitamin D2-enhanced mushrooms increased serum 25-hydroxyvitamin D2 (25(OH)D2) by 128 % from baseline (3·9 (sd 1·9) nmol/l; P < 0·05). Serum 25(OH)D3 increased significantly in the vitamin D3 capsule group (a 55 % increase from a baseline of 44.0 (sd 17·1) nmol/l; P < 0·05). Vitamin D status (25(OH)D) was affected only in the vitamin D3 group. Plasminogen activator inhibitor-1 was lowered by vitamin D2 intake. Vitamin D2 from enhanced mushrooms was bioavailable and increased serum 25(OH)D2 concentration with no significant effect on 25(OH)D3 or total 25(OH)D.

  5. D2: major subgenotype of hepatitis B virus in Russia and the Baltic region.

    PubMed

    Tallo, Tatjana; Tefanova, Valentina; Priimägi, Ljudmilla; Schmidt, Jelena; Katargina, Olga; Michailov, Michail; Mukomolov, Sergey; Magnius, Lars; Norder, Heléne

    2008-08-01

    Complete or almost complete hepatitis B virus (HBV) genomes were sequenced for 13 genotype A and 42 genotype D strains from the former USSR. The strains were classifiable within subgenotypes A2, D1, D2 and D3. Comparison of the deduced gene products for the four ORFs of 89 genotype D strains revealed 27 subgenotype-specific residues, and a region spanning residues 58-128 in the spacer region of the P gene could be used to distinguish between D1 and D4. This enabled the allocation to subgenotype of strains with partially sequenced genomes. D2 was dominating, while D3 was found in low frequency in the whole region. D1 was most prevalent in the Middle Asian Republics. Mean inter-subgenotype divergences between D1 and D2, D1 and D3 and D2 and D3 were 2.7, 3.4 and 3.4 %, respectively. The intra-subgenotype divergence was 0.4, 1.1, 1.0 and 1.8 % for A2, D1, D2 and D3, respectively. All D1 and D3 strains encoded subtype ayw2, whereas most D2 strains encoded ayw3. Two D2 strains encoded ayw4. Strains with identical S genes were closely related at the level of complete genomes and formed geographically specific clades with low intraclade divergences, possibly indicating past iatrogenic spread. It is not clear whether the finding of four subgenotypes in the area corresponds to separate introductions of the virus or to previous population migrations into the area. An earlier introduction of D3 compared with D2 was supported by its higher intra-subgenotype divergence, while the lower divergence within D1 is probably due to a more recent emergence.

  6. Dopamine D2 receptor over-expression alters behavior and physiology in Drd2-EGFP mice

    PubMed Central

    Kramer, Paul F.; Christensen, Christine H.; Hazelwood, Lisa A.; Dobi, Alice; Bock, Roland; Sibley, David R.; Mateo, Yolanda; Alvarez, Veronica A.

    2011-01-01

    BAC transgenic mice expressing the fluorescent reporter protein EGFP under the control of the D1 and D2 dopamine receptor promoters (Drd1-EGFP and Drd2-EGFP) have been widely used to study striatal function and have contributed to our understanding of the physiological and pathological function of the basal ganglia. These tools were produced and promptly made available to address questions in a cell-specific manner that has transformed the way we frame hypotheses in neuroscience. However, these mice have not been fully characterized until now. We found that Drd2-EGFP mice display a ~40% increase in membrane expression of the dopamine D2 receptor (D2R) and a two-fold increase in D2R mRNA levels in the striatum when compared to wild-type and Drd1-EGFP mice D2R over-expression was accompanied by behavioral hypersensitivity to D2R-like agonists, as well as enhanced electrophysiological responses to D2R activation in midbrain dopaminergic neurons. DA transients evoked by stimulation in the nucleus accumbens showed slower clearance in Drd2-EGFP mice and cocaine actions on DA clearance were impaired in these mice. Thus, it was not surprising to find that Drd2-EGFP mice were hyperactive when exposed to a novel environment and locomotion was suppressed by acute cocaine administration. All together, this study demonstrates that Drd2-EGFP mice over-express D2R and have altered dopaminergic signaling that fundamentally differentiates them from wild-type and Drd1-EGFP mice. PMID:21209197

  7. Loss of dopamine D2 receptors increases parvalbumin-positive interneurons in the anterior cingulate cortex.

    PubMed

    Graham, Devon L; Durai, Heather H; Garden, Jamie D; Cohen, Evan L; Echevarria, Franklin D; Stanwood, Gregg D

    2015-02-18

    Disruption to dopamine homeostasis during brain development has been implicated in a variety of neuropsychiatric disorders, including depression and schizophrenia. Inappropriate expression or activity of GABAergic interneurons are common features of many of these disorders. We discovered a persistent upregulation of GAD67+ and parvalbumin+ neurons within the anterior cingulate cortex of dopamine D2 receptor knockout mice, while other GABAergic interneuron markers were unaffected. Interneuron distribution and number were not altered in the striatum or in the dopamine-poor somatosensory cortex. The changes were already present by postnatal day 14, indicating a developmental etiology. D2eGFP BAC transgenic mice demonstrated the presence of D2 receptor expression within a subset of parvalbumin-expressing cortical interneurons, suggesting the possibility of a direct cellular mechanism through which D2 receptor stimulation regulates interneuron differentiation or survival. D2 receptor knockout mice also exhibited decreased depressive-like behavior compared with wild-type controls in the tail suspension test. These data indicate that dopamine signaling modulates interneuron number and emotional behavior and that developmental D2 receptor loss or blockade could reveal a potential mechanism for the prodromal basis of neuropsychiatric disorders.

  8. EFFECTS OF SMOKING ON D2/D3 STRIATAL RECEPTOR AVAILABILITY IN ALCOHOLICS AND SOCIAL DRINKERS

    PubMed Central

    Albrecht, Daniel S.; Kareken, David A.; Yoder, Karmen K.

    2013-01-01

    Objective Studies have reported lower striatal D2/D3 receptor availability in both alcoholics and cigarette smokers relative to healthy controls. These substances are commonly co-abused, yet the relationship between comorbid alcohol/tobacco abuse and striatal D2/D3 receptor availability has not been examined. We sought to determine the degree to which dual abuse of alcohol and tobacco is associated with lower D2/D3 receptor availability. Method Eighty-one subjects (34 nontreatment-seeking alcoholic smokers [NTS-S], 21 social-drinking smokers [SD-S], and 26 social-drinking non-smokers [SD-NS]) received baseline [11C]raclopride scans. D2/D3 binding potential (BPND ≡ Bavail/KD) was estimated for ten anatomically defined striatal regions of interest (ROIs). Results Significant group effects were detected in bilateral pre-commissural dorsal putamen, bilateral pre-commissural dorsal caudate; and bilateral post-commissural dorsal putamen. Post-hoc testing revealed that, regardless of drinking status, smokers had lower D2/D3 receptor availability than non-smoking controls. Conclusions Chronic tobacco smokers have lower striatal D2/D3 receptor availability than non-smokers, independent of alcohol use. Additional studies are needed to identify the mechanisms by which chronic tobacco smoking is associated with striatal dopamine receptor availability. PMID:23649848

  9. CO and D2O chemistry on continuous and discontinuous samaria thin films on Pt(111)

    NASA Astrophysics Data System (ADS)

    Jhang, Jin-Hao; Keil, Simona; Schaefer, Andreas; Zielasek, Volkmar; Bäumer, Marcus

    2016-08-01

    The chemistry of CO and D2O, individually adsorbed or co-adsorbed, on epitaxial thin films of samaria on Pt(111) was studied by temperature-programmed desorption spectroscopy (TPD). Continuous thin films as well as discontinuous films composed of samaria islands on bare Pt(111) were prepared. Their comparative study indicates that Sm2O3 islands provide lattice oxygen at their perimeter for CO oxidation on adjacent exposed Pt area where CO adsorption takes place. CO2 production was observed only on as-prepared discontinuous films. While, in particular on thermally reduced samaria islands, TPD after D2O adsorption revealed D2 production which indicates a pathway for D2O dissociation, no evidence for the water gas shift reaction of CO and residual OD species on the surface was found after co-adsorption of CO and D2O. Instead, interaction between CO and OD species at the perimeter of islands on reduced discontinuous SmOx thin films obviously promotes D2 formation without yielding CO2 as desorbing product.

  10. Cyclin D2 induces proliferation of cardiac myocytes and represses hypertrophy

    SciTech Connect

    Busk, Peter K. . E-mail: pkbu@novonordisk.com; Hinrichsen, Rebecca; Bartkova, Jirina; Hansen, Ane H.; Christoffersen, Tue E.H.; Bartek, Jiri; Haunso, Stig

    2005-03-10

    The myocytes of the adult mammalian heart are considered unable to divide. Instead, mitogens induce cardiomyocyte hypertrophy. We have investigated the effect of adenoviral overexpression of cyclin D2 on myocyte proliferation and morphology. Cardiomyocytes in culture were identified by established markers. Cyclin D2 induced DNA synthesis and proliferation of cardiomyocytes and impaired hypertrophy induced by angiotensin II and serum. At the molecular level, cyclin D2 activated CDK4/6 and lead to pRB phosphorylation and downregulation of the cell cycle inhibitors p21{sup Waf1/Cip1} and p27{sup Kip1}. Expression of the CDK4/6 inhibitor p16 inhibited proliferation and cyclin D2 overexpressing myocytes became hypertrophic under such conditions. Inhibition of hypertrophy by cyclin D2 correlated with downregulation of p27{sup Kip1}. These data show that hypertrophy and proliferation are highly related processes and suggest that cardiomyocyte hypertrophy is due to low amounts of cell cycle activators unable to overcome the block imposed by cell cycle inhibitors. Cell cycle entry upon hypertrophy may be converted to cell division by increased expression of activators such as cyclin D2.

  11. High pressure-assisted encapsulation of vitamin D2 in reassembled casein micelles

    NASA Astrophysics Data System (ADS)

    Menéndez-Aguirre, O.; Stuetz, W.; Grune, T.; Kessler, A.; Weiss, J.; Hinrichs, J.

    2011-03-01

    For the encapsulation of vitamin D2, native casein micelles and vitamin D2 with or without additional Ca2+-Pi were treated at 600 MPa and 37 °C for 60 min. The pressure release rate was set at 20 or 600 MPa/min. Vitamin D2 was quantified by reversed-phase high-performance liquid chromatography, and physical properties of the micelles were analysed by photon correlation spectroscopy. The results demonstrate that simultaneous application of Ca2+-Pi and high pressure treatment with a fast release rate significantly increased loading of vitamin D2 per casein by 6.9-fold. The addition of Ca2+-Pi enhanced micelle aggregation and the vitamin was entrapped within the formed aggregates. However, high pressure treatment without Ca2+-Pi with a slow pressure release rate revealed similar results, increasing vitamin D2 per casein by 6.7-fold. The vitamin D2 loading in reassembled casein micelles is supposed to be due to hydrophobic interactions between the hydrophobic domains of the micelles.

  12. Allelic association of the D2 dopamine receptor gene with receptor-binding characteristics in alcoholism

    SciTech Connect

    Noble, E.P.; Blum, K.; Ritchie, T.; Montgomery, A.; Sheridan, P.J. )

    1991-07-01

    The allelic association of the human D2 dopamine receptor gene with the binding characteristics of the D2 dopamine receptor was determined in 66 brains of alcoholic and non-alcoholic subjects. In a blinded experiment, DNA from the cerebral cortex was treated with the restriction endonuclease Taql and probed with a 1.5-kilobase (kb) digest of a clone (lambda hD2G1) of the human D2 dopamine receptor gene. The binding characteristics (Kd (binding affinity) and Bmax (number of binding sites)) of the D2 dopamine receptor were determined in the caudate nuclei of these brains using tritiated spiperone as the ligand. The adjusted Kd was significantly lower in alcoholic than in nonalcoholic subjects. In subjects with the A1 allele, in whom a high association with alcoholism was found, the Bmax was significantly reduced compared with the Bmax of subjects with the A2 allele. Moreover, a progressively reduced Bmax was found in subjects with A2/A2, A1/A2, and A1/A1 alleles, with subjects with A2/A2 having the highest mean values, and subjects with A1/A1, the lowest. The polymorphic pattern of the D2 dopamine receptor gene and its differential expression of receptors suggests the involvement of the dopaminergic system in conferring susceptibility to at least one subtype of severe alcoholism.

  13. Loss of Dopamine D2 Receptors Increases Parvalbumin-Positive Interneurons in the Anterior Cingulate Cortex

    PubMed Central

    2015-01-01

    Disruption to dopamine homeostasis during brain development has been implicated in a variety of neuropsychiatric disorders, including depression and schizophrenia. Inappropriate expression or activity of GABAergic interneurons are common features of many of these disorders. We discovered a persistent upregulation of GAD67+ and parvalbumin+ neurons within the anterior cingulate cortex of dopamine D2 receptor knockout mice, while other GABAergic interneuron markers were unaffected. Interneuron distribution and number were not altered in the striatum or in the dopamine-poor somatosensory cortex. The changes were already present by postnatal day 14, indicating a developmental etiology. D2eGFP BAC transgenic mice demonstrated the presence of D2 receptor expression within a subset of parvalbumin-expressing cortical interneurons, suggesting the possibility of a direct cellular mechanism through which D2 receptor stimulation regulates interneuron differentiation or survival. D2 receptor knockout mice also exhibited decreased depressive-like behavior compared with wild-type controls in the tail suspension test. These data indicate that dopamine signaling modulates interneuron number and emotional behavior and that developmental D2 receptor loss or blockade could reveal a potential mechanism for the prodromal basis of neuropsychiatric disorders. PMID:25393953

  14. Cyclin D2 is an FSH-responsive gene involved in gonadal cell proliferation and oncogenesis.

    PubMed

    Sicinski, P; Donaher, J L; Geng, Y; Parker, S B; Gardner, H; Park, M Y; Robker, R L; Richards, J S; McGinnis, L K; Biggers, J D; Eppig, J J; Bronson, R T; Elledge, S J; Weinberg, R A

    1996-12-05

    THE D-type cyclins (D1, D2 and D3) are critical governors of the cell-cycle clock apparatus during the G1 phase of the mammalian cell cycle. These three D-type cyclins are expressed in overlapping, apparently redundant fashion in the proliferating tissues. To investigate why mammalian cells need three distinct D-type cyclins, we have generated mice bearing a disrupted cyclin D2 gene by using gene targeting in embryonic stem cells. Cyclin D2-deficient females are sterile owing to the inability of ovarian granulosa cells to proliferate normally in response to follicle-stimulating hormone (FSH), whereas mutant males display hypoplastic testes. In ovarian granulosa cells, cyclin D2 is specifically induced by FSH via a cyclic-AMP-dependent pathway, indicating that expression of the various D-type cyclins is under control of distinct intracellular signalling pathways. The hypoplasia seen in cyclin D2(-/-) ovaries and testes prompted us to examine human cancers deriving from corresponding tissues. We find that some human ovarian and testicular tumours contain high levels of cyclin D2 messenger RNA.

  15. Nuclear Magnetic Resonance Evidence using D2O for Structured Water in Muscle and Brain

    PubMed Central

    Cope, Freeman W.

    1969-01-01

    The electric quadrupole moment of the deuterium nucleus provides a nuclear magnetic resonance (NMR) probe of electric field gradients, and thereby of organization of tissue water. 8-17% of H2O in rat muscle and brain was replaced by D2O from 50% deuterated drinking water. The peak height of the steady-state NMR spectrum of D in muscle water was 74% lower than that of an equal concentration of D2O in liquid water. Longitudinal NMR relaxation times (T1) of D in water of muscle and brain averaged 0.092 and 0.131 sec, respectively, compared with 0.47 sec in D2O in liquid water. Transverse NMR relaxation times (T2) averaged 0.009 and 0.022 sec in D2O of muscle and brain, respectively, compared with 0.45 sec in D2O in liquid water. These differences cannot be explained by paramagnetic ions or by magnetic inhomogeneities, which leaves increased organization of tissue water as the only tenable hypothesis. Evidence was also obtained that 27% of muscle water and 13% of brain water exist as a separate fraction with T2 of D2O less than 2 × 10-3 sec, which implies an even higher degree of structure. Each of the two fractions may consist of multiple subfractions of differing structure. PMID:5780710

  16. Measurement of 25-hydroxyvitamin D2&3 and 1, 25-dihydroxyvitamin D2&3 by Tandem Mass Spectrometry: A Primate Multispecies Comparison

    PubMed Central

    Ziegler, Toni E.; Kapoor, Amita; Hedman, Curtis J.; Binkley, Neil; Kemnitz, Joseph W.

    2015-01-01

    Vitamin D metabolites are widely studied for their roles in bone health, immune functions and other potential physiologic roles in humans. However, the optimal blood levels of vitamin D metabolites are still unclear. Various methods for measuring vitamin D metabolites have been used and recently liquid chromatography tandem mass spectroscopy (LC-MS/MS) has been adopted as the gold standard for vitamin D metabolite measurement. Here we report the use of LC-MS/MS to measure 25-hydroxyvitamin D (25(OH)D2&3), and 1,25-dihydroxyvitamin D (1,25(OH)2D2&3), in three laboratory nonhuman primate species: common marmoset (Callithrix jacchus), rhesus macaque (Macaca mulatta), and cynomolgus macaque (Macaca fascicularis), and compare them to humans using the same technique. The nonhuman primates showed blood levels for 25(OH)D3 and 1,25(OH)2D3 significantly higher than human values with marmosets having the highest levels. Marmoset samples showed significantly more variability among individuals than those from macaques for both metabolites, but all three nonhuman primate species exhibited large variation within species for both 25(OH)D2&3 and 1,25(OH)2D2&3. Marmoset females had significantly lower values than the males for 25(OH)D3, while rhesus males showed a significant decrease in 25(OH)D3 with age. The most striking finding is the variation within species for vitamin D levels even in laboratory primates that have a controlled diet, UV exposure, and in some cases, genetic constraints. Similar variation in 25(OH)D responses to a fixed dose of oral vitamin D supplementation has been reported in humans. We suggest that these species can provide primate models for examining the factors influencing variation in the levels of vitamin D necessary for human and nonhuman primate health. PMID:25845705

  17. An alternative pathway of vitamin D metabolism. Cytochrome P450scc (CYP11A1)-mediated conversion to 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2.

    PubMed

    Slominski, Andrzej; Semak, Igor; Wortsman, Jacobo; Zjawiony, Jordan; Li, Wei; Zbytek, Blazej; Tuckey, Robert C

    2006-07-01

    We report an alternative, hydroxylating pathway for the metabolism of vitamin D2 in a cytochrome P450 side chain cleavage (P450scc; CYP11A1) reconstituted system. NMR analyses identified solely 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2 derivatives. 20-Hydroxyvitamin D2 was produced at a rate of 0.34 mol x min(-1) x mol(-1) P450scc, and 17,20-dihydroxyvitamin D2 was produced at a rate of 0.13 mol x min(-1) x mol(-1). In adrenal mitochondria, vitamin D2 was metabolized to six monohydroxy products. Nevertheless, aminoglutethimide (a P450scc inhibitor) inhibited this adrenal metabolite formation. Initial testing of metabolites for biological activity showed that, similar to vitamin D2, 20-hydroxyvitamin D2 and 17,20-dihydroxyvitamin D2 inhibited DNA synthesis in human epidermal HaCaT keratinocytes, although to a greater degree. 17,20-Dihydroxyvitamin D2 stimulated transcriptional activity of the involucrin promoter, again to a significantly greater extent than vitamin D2, while the effect of 20-hydroxyvitamin D2 was statistically insignificant. Thus, P450scc can metabolize vitamin D2 to generate novel products, with intrinsic biological activity (at least in keratinocytes).

  18. Effects of the rotational excitation of D2 and of the potential energy surface on the H+ + D2 --> HD + D+ reaction.

    PubMed

    González-Lezana, T; Honvault, P; Jambrina, P G; Aoiz, F J; Launay, J-M

    2009-07-28

    The H(+) + D(2) --> HD + D(+) reaction has been theoretically investigated by means of an exact quantum mechanical approach, a quasiclassical trajectory method, and two statistical methods based in the propagation of either wave functions or trajectories. The study addresses the possible changes on the overall dynamics of the title reaction when the D(2) diatom is rotationally excited to its v = 0, j = 1 state. In addition, the reactivity for the ground rotational state on two different potential energy surfaces (PESs), namely, the surface by Aguado et al. [J. Chem. Phys. 112, 1240 (2000)] and the PES by Kamisaka et al. [J. Chem. Phys. 116, 654 (2002)], is examined. Reaction probabilities and cross sections at 0.524 and 0.1 eV collision energies are calculated. The major differences with respect to the reaction initiated with D(2) in its ground rovibrational state are observed for the lowest collision energy E(c) = 0.1 eV. Differential cross sections have been found to depend to some extend on the PES employed. In addition, at E(c) = 0.1 eV further discrepancies in the total and rotational cross sections are noticeable.

  19. Mechanisms of inverse agonism of antipsychotic drugs at the D(2) dopamine receptor: use of a mutant D(2) dopamine receptor that adopts the activated conformation.

    PubMed

    Wilson, J; Lin, H; Fu, D; Javitch, J A; Strange, P G

    2001-04-01

    The antipsychotic drugs have been shown to be inverse agonists at the D(2) dopamine receptor. We have examined the mechanism of this inverse agonism by making mutations in residue T343 in the base of the sixth transmembrane spanning region of the receptor. T343R, T343S and T343K mutant D(2) dopamine receptors were made and the T343R mutant characterized in detail. The T343R mutant D(2) dopamine receptor exhibits properties of a receptor that resides more in the activated state, namely increased agonist binding affinity (independent of G-protein coupling and dependent on agonist efficacy), increased agonist potency in functional tests (adenylyl cyclase inhibition) and increased inverse agonist effects. The binding of agonists to the mutant receptor also shows sensitivity to sodium ions, unlike the native receptor, so that isomerization of the receptor to its inactive state may be driven by sodium ions. The binding of inverse agonists to the receptor is, however, unaffected by the mutation. We conclude that inverse agonism at this receptor is not achieved by the inverse agonist binding preferentially to the non-activated state of the receptor over the activated state. Rather the inverse agonist appears to bind to all forms of the receptor but then renders the receptor inactive.

  20. Theory and Applications of a Faraday Filter-Based Spectrometer to Measure Sodium Nightglow D2/D1 Intensity Ratios

    NASA Astrophysics Data System (ADS)

    Harrell, S. D.; She, C.; Krueger, D. A.; Yuan, T.; Reising, S. C.

    2008-12-01

    The Chapman mechanism (1939) offers the accepted chemical pathway for the production of excited states of mesospheric sodium, leading to nightglow at two wavelengths: D2 (589.158 nm) and D1 (589.756 nm). While the Chapman mechanism leaves open the possibility that the intensity ratio of the two transitions may vary due to the chemical reaction involving atomic oxygen, early observations by Sipler and Biondi (1978) yielded the value of two within experimental error. Recent work by Slanger et al. (2005), however, showed that not only does the intensity ratio vary, but its value is related to the concentration ratio of atomic oxygen [O] to molecular oxygen [O2]. They proposed a modification of the Chapman mechanism involving two competing chemical pathways for sodium production to account for the observed variation. This paper will describe our compact, Faraday filter-based spectrometer to measure the D2/D1 intensity ratio of the sodium nightglow from the upper mesosphere. The novelty of this method also permits determination of the fractional contributions of the two chemical pathways to test the validity of the modified Chapman mechanism for Na chemistry, as well as to infer information about [O]/[O2]. Since the delineation between the two chemical pathways requires a spectral resolution of 0.0002 nm, this is not possible with any other existing instrument. With this spectrometer deployed at the Colorado State University sodium lidar facility (41°N, 105°W), we expect to be able to measure short-term variations of the sodium nightglow intensity ratio and the chemical pathway fraction, from which [O]/[O2] can be inferred. These observations may yield new insights into mesospheric chemistry, especially for atomic and molecular oxygen, which play a key role in upper atmospheric chemistry and dynamics.

  1. Dopamine D2 receptor availability in opiate addicts at baseline and during naloxone precipitated withdrawal

    SciTech Connect

    Wang, G.J.; Volkow, N.D.; Logan, J. ||

    1996-05-01

    To determine if changes in dopamine activity contribute to the clinical presentation of opiate withdrawal we assessed dopamine (DA) D2 receptor availability in opiate-dependent subjects at baseline and during naloxone-precipitated withdrawal. DA D2 receptor availability was evaluated in eleven male heroine and methadone users using positron emission tomography (PET) and [11-C]raclopride and compared to eleven age matched male control subjects. Nine of the opiate-dependent subjects and two of the control were tested twice after placebo and naloxone (0.02 mg/kg) iv injection 7-10 min. prior to [11-C]raclopride. DA D2 receptor availability was measured using the ratio of the distribution volume in the region of interest (caudate, putamen and ventral striatum) to that in the cerebellum which is a function of B{sub max}/K{sub d}. DA D2 receptor availability in putamen was significantly lower in opiate-dependent subjects (3.44 {plus_minus} 0.4) than that in controls (3.97 {plus_minus} 0.45, p {ge} 0.009). Naloxone induced a short lasting withdrawal in all of the opiate-dependent subjects (79 {plus_minus} 17% of maximum withdrawal), but not in controls, with significant increase in pulse (p {le} 0.006), blood pressure (p {le} 0.0001), lacrimation (p {le} 0.01), muscle twitches (p {le} 0.01), annoyance (p {le} 0.005), anxiety (p {le} 0.0006), restlessness (p {le} 0.0005) and unhappiness (p {le} 0.001). DA D2 receptor availability in basal ganglia after naloxone administration was not different from that of baseline. These results document abnormalities in DA D2 receptors in opiate-dependent subjects. However, DA D2 availability did not change with naloxone-precipitated withdrawal.

  2. Evidence That Sleep Deprivation Downregulates Dopamine D2R in Ventral Striatum in the Human Brain

    SciTech Connect

    Volkow N. D.; Fowler J.; Volkow, N.D.; Tomasi, D.; Wang, G.-J.; Fowler, J.S.; Logan, J.; Benveniste, H.; Kin, R.; Thanos, P.K.; Sergi F.

    2012-03-23

    Dopamine D2 receptors are involved with wakefulness, but their role in the decreased alertness associated with sleep deprivation is unclear. We had shown that sleep deprivation reduced dopamine D2/D3 receptor availability (measured with PET and [{sup 11}C]raclopride in controls) in striatum, but could not determine whether this reflected dopamine increases ([{sup 11}C]raclopride competes with dopamine for D2/D3 receptor binding) or receptor downregulation. To clarify this, we compared the dopamine increases induced by methylphenidate (a drug that increases dopamine by blocking dopamine transporters) during sleep deprivation versus rested sleep, with the assumption that methylphenidate's effects would be greater if, indeed, dopamine release was increased during sleep deprivation. We scanned 20 controls with [{sup 11}C]raclopride after rested sleep and after 1 night of sleep deprivation; both after placebo and after methylphenidate. We corroborated a decrease in D2/D3 receptor availability in the ventral striatum with sleep deprivation (compared with rested sleep) that was associated with reduced alertness and increased sleepiness. However, the dopamine increases induced by methylphenidate (measured as decreases in D2/D3 receptor availability compared with placebo) did not differ between rested sleep and sleep deprivation, and were associated with the increased alertness and reduced sleepiness when methylphenidate was administered after sleep deprivation. Similar findings were obtained by microdialysis in rodents subjected to 1 night of paradoxical sleep deprivation. These findings are consistent with a downregulation of D2/D3 receptors in ventral striatum with sleep deprivation that may contribute to the associated decreased wakefulness and also corroborate an enhancement of D2 receptor signaling in the arousing effects of methylphenidate in humans.

  3. Dopamine inhibits somatolactin gene expression in tilapia pituitary cells through the dopamine D2 receptors.

    PubMed

    Jiang, Quan; Lian, Anji; He, Qi

    2016-07-01

    Dopamine (DA) is an important neurotransmitter in the central nervous system of vertebrates and possesses key hypophysiotropic functions. Early studies have shown that DA has a potent inhibitory effect on somatolactin (SL) release in fish. However, the mechanisms responsible for DA inhibition of SL gene expression are largely unknown. To this end, tilapia DA type-1 (D1) and type-2 (D2) receptor transcripts were examined in the neurointermediate lobe (NIL) of the tilapia pituitary by real-time PCR. In tilapia, DA not only was effective in inhibiting SL mRNA levels in vivo and in vitro, but also could abolish pituitary adenylate cyclase-activating polypeptide (PACAP)- and salmon gonadotropin-releasing hormone (sGnRH)-stimulated SL gene expression at the pituitary level. In parallel studies, the specific D2 receptor agonists quinpirole and bromocriptine could mimic the DA-inhibited SL gene expression. Furthermore, the D2 receptor antagonists domperidone and (-)-sulpiride could abolish the SL response to DA or the D2 agonist quinpirole, whereas D1 receptor antagonists SCH23390 and SKF83566 were not effective in this respect. In primary cultures of tilapia NIL cells, D2 agonist quinpirole-inhibited cAMP production could be blocked by co-treatment with the D2 antagonist domperidone and the ability of forskolin to increase cAMP production was also inhibited by quinpirole. Using a pharmacological approach, the AC/cAMP pathway was shown to be involved in quinpirole-inhibited SL mRNA expression. These results provide evidence that DA can directly inhibit SL gene expression at the tilapia pituitary level via D2 receptor through the AC/cAMP-dependent mechanism.

  4. Steroid-independent male sexual behavior in B6D2F2 male mice.

    PubMed

    McInnis, Christine M; Venu, Samitha; Park, Jin Ho

    2016-09-01

    It is well established that male sexual behavior (MSB) is regulated by gonadal steroids; however, individual differences in MSB, independent of gonadal steroids, are prevalent across a wide range of species, and further investigation is necessary to advance our understanding of steroid-independent MSB. Studies utilizing B6D2F1 hybrid male mice in which a significant proportion retain MSB after long-term orchidectomy, identified as steroid-independent-maters (SI-maters), have begun to unravel the genetic underpinnings of steroid-independent MSB. A recent study demonstrated that steroid-independent MSB is a heritable behavioral phenotype that is mainly passed down from B6D2F1 hybrid SI-maters when crossed with C57BL6J female mice. To begin to uncover whether the strain of the dam plays a role in the inheritance of steroid-independent MSB, B6D2F1 hybrid females were crossed with B6D2F1 hybrid males. While the present study confirms the finding that steroid-independent MSB is a heritable behavioral phenotype and that SI-mater sires are more likely to pass down some components of MSB than SI-non-maters to their offspring, it also reveals that the B6D2F2 male offspring that were identified as SI-maters that displayed the full repertoire of steroid-independent MSB had the same probability of being sired from either a B6D2F1 SI-mater or SI-non-mater. These results, in conjunction with previous findings, indicate that the specific chromosomal loci pattern that codes for steroid-independent MSB in the B6D2F2 male offspring may result regardless of whether the father was a SI-mater or SI-non-mater, and that the maternal strain may be an important factor in the inheritance of steroid-independent MSB.

  5. Age-dependent kinetics of dentate gyrus neurogenesis in the absence of cyclin D2

    PubMed Central

    2012-01-01

    Background Adult neurogenesis continuously adds new neurons to the dentate gyrus and the olfactory bulb. It involves the proliferation and subsequent differentiation of neuronal progenitors, and is thus closely linked to the cell cycle machinery. Cell cycle progression is governed by the successive expression, activation and degradation of regulatory proteins. Among them, D-type cyclins control the exit from the G1 phase of the cell cycle. Cyclin D2 (cD2) has been shown to be required for the generation of new neurons in the neurogenic niches of the adult brain. It is differentially expressed during hippocampal development, and adult cD2 knock out (cD2KO) mice virtually lack neurogenesis in the dentate gyrus and olfactory bulb. In the present study we examined the dynamics of postnatal and adult neurogenesis in the dentate gyrus (DG) of cD2KO mice. Animals were injected with bromodeoxyuridine at seven time points during the first 10 months of life and brains were immunohistochemically analyzed for their potential to generate new neurons. Results Compared to their WT litters, cD2KO mice had considerably reduced numbers of newly born granule cells during the postnatal period, with neurogenesis becoming virtually absent around postnatal day 28. This was paralleled by a reduction in granule cell numbers, in the volume of the granule cell layer as well as in apoptotic cell death. CD2KO mice did not show any of the age-related changes in neurogenesis and granule cell numbers that were seen in WT litters. Conclusions The present study suggests that hippocampal neurogenesis becomes increasingly dependent on cD2 during early postnatal development. In cD2KO mice, hippocampal neurogenesis ceases at a time point at which the tertiary germinative matrix stops proliferating, indicating that cD2 becomes an essential requirement for ongoing neurogenesis with the transition from developmental to adult neurogenesis. Our data further support the notion that adult neurogenesis

  6. Dose-Response Effect of Sunlight on Vitamin D2 Production in Agaricus bisporus Mushrooms.

    PubMed

    Urbain, Paul; Jakobsen, Jette

    2015-09-23

    The dose response effect of UV-B irradiation from sunlight on vitamin D2 content of sliced Agaricus bisporus (white button mushroom) during the process of sun-drying was investigated.Real-time UV-B and UV-A data were obtained using a high-performance spectroradiometer. During the first hour of sunlight exposure, the vitamin D2 content of the mushrooms increased in a linear manner, with concentrations increasing from 0.1 μg/g up to 3.9 ± 0.8 μg/g dry weight (DW). At the subsequent two measurements one and 3 h later, respectively, a plateau was reached. Two hours of additional exposure triggered a significant decline in vitamin D2 content. After just 15 min of sun exposure and an UV-B dose of 0.13 J/cm(2), the vitamin D2 content increased significantly to 2.2 ± 0.5 μg/g DW (P < 0.0001), which is equivalent to 17.6 μg (704 IU) vitamin D2 per 100 g of fresh mushrooms and comparable to levels found in fatty fish like the Atlantic salmon.

  7. The Roles of Dopamine D2 Receptor in the Social Hierarchy of Rodents and Primates.

    PubMed

    Yamaguchi, Yoshie; Lee, Young-A; Kato, Akemi; Jas, Emanuel; Goto, Yukiori

    2017-02-24

    Dopamine (DA) plays significant roles in regulation of social behavior. In social groups of humans and other animals, social hierarchy exists, which is determined by several behavioral characteristics such as aggression and impulsivity as well as social affiliations. In this study, we investigated the effects of pharmacological blockade of DA D2 receptor on social hierarchy of Japanese macaque and mouse social groups. We found acute administration of the D2 antagonist, sulpiride, in socially housed Japanese macaques attenuated social dominance when the drug was given to high social class macaques. A similar attenuation of social dominance was observed in high social class mice with D2 antagonist administration. In contrast, D2 antagonist administration in low social class macaque resulted in more stable social hierarchy of the group, whereas such effect was not observed in mouse social group. These results suggest that D2 receptor signaling may play important roles in establishment and maintenance of social hierarchy in social groups of several species of animals.

  8. Chromosomal aadD2 encodes an aminoglycoside nucleotidyltransferase in Bacillus clausii.

    PubMed

    Bozdogan, Bülent; Galopin, Sébastien; Gerbaud, Guy; Courvalin, Patrice; Leclercq, Roland

    2003-04-01

    Bacillus clausii SIN is one of the four strains of B. clausii composing a probiotic administered to humans for the prevention of gastrointestinal side effects due to oral antibiotic therapy. The strain is resistant to kanamycin, tobramycin, and amikacin. A gene conferring aminoglycoside resistance was cloned into Escherichia coli and sequenced. The gene, called aadD2, encoding a putative 246-amino acid protein, shared 47% identity with ant(4')-Ia from Staphylococcus aureus, which encodes an aminoglycoside 4'-O-nucleotidyltransferase. Phosphocellulose paper-binding assays indicated that the gene product was responsible for nucleotidylation of kanamycin, tobramycin, and amikacin. The aadD2 gene was detected by DNA-DNA hybridization in the three other strains of the probiotic mixture and in the reference strain B. clausii DSM8716, although it did not confer resistance in these strains. Mutations in the sequence of the putative promoter for aadD2 from B. clausii SIN resulted in higher identity with consensus promoter sequences and may account for aminoglycoside resistance in that strain. The aadD2 gene was chromosomally located in all strains and was not transferable by conjugation. These data indicate that chromosomal aadD2 is specific to B. clausii.

  9. Dopamine D(2)-class receptor supersensitivity as reflected in Ca2+ current modulation in neostriatal neurons.

    PubMed

    Prieto, G A; Perez-Burgos, A; Fiordelisio, T; Salgado, H; Galarraga, E; Drucker-Colin, R; Bargas, J

    2009-12-01

    The loss of dopaminergic neurons followed by dopamine (DA) depletion in the neostriatum is a hallmark of Parkinson's disease. Among other changes, DA D(2)-receptor class (D(2)R-class) supersensitivity is a result of striatal DA depletion. Pharmacological, biochemical and behavioral data have documented this phenomenon, but clear electrophysiological-functional correlates are still lacking. This work describes an electrophysiological correlate of D(2)R-class supersensitivity in DA-depleted striata after unilateral 6-hydroxydopamine (6-OHDA) lesions in the rat substantia nigra compacta (SNc). Ca2+ current modulation mediated by D(2)R-class activation reflected an altered sensitivity. Thus, while the concentration-response relationship (C-R plot) from control striata was better fit with a two sites model, the C-R plot obtained from DA-depleted striata was better fit by a three sites model, exhibited a considerable leftward shift, and presented an increased maximal response. Because Ca2+ current modulation by D(2)R-class activation is involved in the control of spiny neurons excitability and their synaptic GABA release, the present findings may help to explain several functional changes found in the striatal circuitry after dopaminergic denervation.

  10. Effect of D2O on growth properties and chemical structure of annual ryegrass (Lolium multiflorum)

    SciTech Connect

    Evans, Barbara R; Bali, Garima; Reeves, David T; O'Neill, Hugh Michael; Sun, Qining; Shah, Riddhi S; Ragauskas, Arthur

    2014-01-01

    In present paper, we report the production and detailed structural analysis of deuterium-enriched rye grass (Lolium multiflorum) for neutron scattering experiments. An efficient method to produce deuterated biomass was developed by designing hydroponic perfusion chambers. In preliminary studies, the partial deuterated rye samples were grown in increasing levels of D2O to study the seed germination and the level of deuterium incorporation as a function of D2O concentration. Solution NMR method indicated 36.9 % deuterium incorporation in 50 % D2O grown annual rye samples and further significant increase in the deuterium incorporation level was observed by germinating the rye seedlings in H2O and growing in 50 % D2O inside the perfusion chambers. Moreover, in an effort to compare the substrate characteristics related to enzymatic hydrolysis on deuterated and protiated version of biomass, annual rye grown in 50 % D2O was selected for detailed biomass characterization studies. The compositional analyses, degree of polymerization and cellulose crystallinity were compared with its protiated control. The cellulose molecular weight indicated slight variation with deuteration; however, hemicellulose molecular weights and cellulose crystallinity remain unaffected with the deuteration. Besides the minor differences in biomass components, the development of deuterated biomass for neutron scattering application is essential to understand the complex biomass conversion processes.

  11. Serotonin-S2 and dopamine-D2 receptors are the same size in membranes

    SciTech Connect

    Brann, M.R.

    1985-12-31

    Target size analysis was used to compare the sizes of serotonin-S2 and dopamine-D2 receptors in rat brain membranes. The sizes of these receptors were standardized by comparison with the muscarinic receptor, a receptor of known size. The number of serotonin-S2 receptors labeled with (3H)ketanserin or (3H)spiperone in frontal cortex decreased as an exponential function of radiation dose, and receptor affinity was not affected. The number of dopamine-D2 receptors labeled with (3H)spiperone in striatum also decreased as an exponential function of radiation dose, and D2 and S2 receptors were equally sensitive to radiation. In both striatum and frontal cortex, the number of muscarinic receptors labeled with (3H)QNB decreased as an exponential function of radiation dose, and were much less sensitive to radiation than S2 and D2 receptors. These data indicate that in rat brain membranes, S2 and D2 receptors are of similar size, and both molecules are much larger than the muscarinic receptor.

  12. Dopamine D2-Like Receptors Modulate Unconditioned Fear: Role of the Inferior Colliculus

    PubMed Central

    de Oliveira, Amanda Ribeiro; Colombo, Ana Caroline; Muthuraju, Sangu; Almada, Rafael Carvalho; Brandão, Marcus Lira

    2014-01-01

    Background A reduction of dopamine release or D2 receptor blockade in the terminal fields of the mesolimbic system clearly reduces conditioned fear. Injections of haloperidol, a preferential D2 receptor antagonist, into the inferior colliculus (IC) enhance the processing of unconditioned aversive information. However, a clear characterization of the interplay of D2 receptors in the mediation of unconditioned and conditioned fear is still lacking. Methods The present study investigated the effects of intra-IC injections of the D2 receptor-selective antagonist sulpiride on behavior in the elevated plus maze (EPM), auditory-evoked potentials (AEPs) to loud sounds recorded from the IC, fear-potentiated startle (FPS), and conditioned freezing. Results Intra-IC injections of sulpiride caused clear proaversive effects in the EPM and enhanced AEPs induced by loud auditory stimuli. Intra-IC sulpiride administration did not affect FPS or conditioned freezing. Conclusions Dopamine D2-like receptors of the inferior colliculus play a role in the modulation of unconditioned aversive information but not in the fear-potentiated startle response. PMID:25133693

  13. The infrared spectrum of the Ne-C2D2 complex.

    PubMed

    Moazzen-Ahmadi, N; McKellar, A R W; Fernández, Berta; Farrelly, David

    2015-11-28

    Infrared spectra of Ne-C2D2 are observed in the region of the ν3 fundamental band (asymmetric C-D stretch, ≈2440 cm(-1)) using a tunable optical parametric oscillator to probe a pulsed supersonic slit jet expansion from a cooled nozzle. Like helium-acetylene, this system lies close to the free rotor limit, making analysis tricky because stronger transitions tend to pile up close to monomer (C2D2) rotation-vibration transitions. Assignments are aided by predicted rotational energies calculated from a published ab initio intermolecular potential energy surface. The analysis extends up to the j = 3←2 band, where j labels C2D2 rotation within the dimer, and is much more complete than the limited infrared assignments previously reported for Ne-C2H2 and Ne-C2HD. Two previous microwave transitions within the j = 1 state of Ne-C2D2 are reassigned. Coriolis model fits to the theoretical levels and to the spectrum are compared. Since the variations observed as a function of C2D2 vibrational excitation are comparable to those noted between theory and experiment, it is evident that more detailed testing of theory will require vibrational averaging over the acetylene intramolecular modes.

  14. Dopamine D2 receptors preferentially regulate the development of light responses of the inner retina

    PubMed Central

    Tian, Ning; Xu, Hong-ping; Wang, Ping

    2014-01-01

    Retinal light responsiveness measured via electroretinography undergoes developmental modulation and is thought to be critically regulated by both visual experience and dopamine. The primary goal of this study is to determine whether the dopamine D2 receptor regulates the visual experience-dependent functional development of the retina. Accordingly, we recorded electroretinograms from wild type mice and mice with a genetic deletion of the gene that encodes the dopamine D2 receptor raised under normal cyclic light conditions and constant darkness. Our results demonstrate that mutation of the dopamine D2 receptors preferentially increases the amplitude of the inner retinal light responses evoked by high intensity light measured as oscillatory potentials in adult mice. During postnatal development, all three major components of electroretinograms, the a-wave, b-wave and oscillatory potentials, increase with age. Comparatively, mutation of the dopamine D2 receptors preferentially reduces the age-dependent increase of b-waves evoked by low intensity light. Light deprivation from birth reduces the amplitude of b-waves and completely diminishes the increased amplitude of oscillatory potentials. Taken together, these results demonstrate that the dopamine D2 receptor plays an important role in the activity-dependent functional development of the mouse retina. PMID:25393815

  15. Role of dopamine D2 receptors in optimizing choice strategy in a dynamic and uncertain environment

    PubMed Central

    Kwak, Shinae; Huh, Namjung; Seo, Ji-Seon; Lee, Jung-Eun; Han, Pyung-Lim; Jung, Min W.

    2014-01-01

    In order to investigate roles of dopamine receptor subtypes in reward-based learning, we examined choice behavior of dopamine D1 and D2 receptor-knockout (D1R-KO and D2R-KO, respectively) mice in an instrumental learning task with progressively increasing reversal frequency and a dynamic two-armed bandit task. Performance of D2R-KO mice was progressively impaired in the former as the frequency of reversal increased and profoundly impaired in the latter even with prolonged training, whereas D1R-KO mice showed relatively minor performance deficits. Choice behavior in the dynamic two-armed bandit task was well explained by a hybrid model including win-stay-lose-switch and reinforcement learning terms. A model-based analysis revealed increased win-stay, but impaired value updating and decreased value-dependent action selection in D2R-KO mice, which were detrimental to maximizing rewards in the dynamic two-armed bandit task. These results suggest an important role of dopamine D2 receptors in learning from past choice outcomes for rapid adjustment of choice behavior in a dynamic and uncertain environment. PMID:25389395

  16. Dual role of dopamine D(2)-like receptors in the mediation of conditioned and unconditioned fear.

    PubMed

    Brandão, Marcus Lira; de Oliveira, Amanda Ribeiro; Muthuraju, Sangu; Colombo, Ana Caroline; Saito, Viviane Mitsuko; Talbot, Teddy

    2015-11-14

    A reduction of dopamine release or D2 receptor blockade in the terminal fields of the mesolimbic system, particularly the amygdala, clearly reduces conditioned fear. Similar D2 receptor antagonism in the neural substrates of fear in the midbrain tectum attenuates the processing of unconditioned aversive information. However, the implications of the interplay between opposing actions of dopamine in the rostral and caudal segments of the dopaminergic system are still unclear. Previous studies from this laboratory have reported the effects of dopaminergic drugs on behavior in rats in the elevated plus maze, auditory-evoked potentials (AEPs) recorded from the midbrain tectum, fear-potentiated startle, and conditioned freezing. These findings led to an interesting framework on the functional roles of dopamine in both anxiety and fear states. Dopamine D2 receptor inhibition in the terminal fields of the mesolimbic dopamine system generally causes anxiolytic-like effects, whereas the activity of midbrain substrates of unconditioned fear are enhanced by D2 receptor antagonists, suggesting that D2 receptor-mediated mechanisms play opposing roles in fear/anxiety processes, depending on the brain region under study. Dopamine appears to mediate conditioned fear by acting at rostral levels of the brain and regulate unconditioned fear at the midbrain level, likely by reducing the sensorimotor gating of aversive events.

  17. The Roles of Dopamine D2 Receptor in the Social Hierarchy of Rodents and Primates

    PubMed Central

    Yamaguchi, Yoshie; Lee, Young-A.; Kato, Akemi; Jas, Emanuel; Goto, Yukiori

    2017-01-01

    Dopamine (DA) plays significant roles in regulation of social behavior. In social groups of humans and other animals, social hierarchy exists, which is determined by several behavioral characteristics such as aggression and impulsivity as well as social affiliations. In this study, we investigated the effects of pharmacological blockade of DA D2 receptor on social hierarchy of Japanese macaque and mouse social groups. We found acute administration of the D2 antagonist, sulpiride, in socially housed Japanese macaques attenuated social dominance when the drug was given to high social class macaques. A similar attenuation of social dominance was observed in high social class mice with D2 antagonist administration. In contrast, D2 antagonist administration in low social class macaque resulted in more stable social hierarchy of the group, whereas such effect was not observed in mouse social group. These results suggest that D2 receptor signaling may play important roles in establishment and maintenance of social hierarchy in social groups of several species of animals. PMID:28233850

  18. Deuterium oxide (D2O) enhances the photosensitivity of Stentor coeruleus

    SciTech Connect

    Iwatsuki, K.; Song, P.S.

    1985-12-01

    Stentor coeruleus exhibits negative phototaxis and step-up photophobic response (avoiding reaction) to visible light (maximum at 610-620 nm in both responses). In the presence of deuterium oxide (D2O) the step-up photophobic response was markedly enhanced, whereas the phototactic orientation response was inhibited. The induction time for the step-up photophobic response was longer in D2O than in H2O, and the duration of ciliary reversal for the response was also longer in D2O than in H2O, indicating that certain steps of the sensory transduction chain are subject to solvent deuterium isotope effects. The enhancement of the step-up photophobic response in D2O was canceled by LaCl3, while the inhibition of the phototactic orientation response in D2O was partially removed by LaCl3, even though LaCl3 did not affect the phototactic orientation response. These results suggest that the sensory transduction mechanisms for the two photoresponses are different, although the photoreceptors (stentorin) are the same.

  19. Deuterium oxide (D2O) enhances the photosensitivity of Stentor coeruleus.

    PubMed

    Iwatsuki, K; Song, P S

    1985-12-01

    Stentor coeruleus exhibits negative phototaxis and step-up photophobic response (avoiding reaction) to visible light (maximum at 610-620 nm in both responses). In the presence of deuterium oxide (D2O) the step-up photophobic response was markedly enhanced, whereas the phototactic orientation response was inhibited. The induction time for the step-up photophobic response was longer in D2O than in H2O, and the duration of ciliary reversal for the response was also longer in D2O than in H2O, indicating that certain steps of the sensory transduction chain are subject to solvent deuterium isotope effects. The enhancement of the step-up photophobic response in D2O was canceled by LaCl3, while the inhibition of the phototactic orientation response in D2O was partially removed by LaCl3, even though LaCl3 did not affect the phototactic orientation response. These results suggest that the sensory transduction mechanisms for the two photoresponses are different, although the photoreceptors (stentorin) are the same.

  20. Water Extract of Fructus Hordei Germinatus Shows Antihyperprolactinemia Activity via Dopamine D2 Receptor

    PubMed Central

    Wang, Xiong; Ma, Li; Zhang, En-jing; Zou, Ji-li; Guo, Hao; Peng, Si-wei; Wu, Jin-hu

    2014-01-01

    Objective. Fructus Hordei Germinatus is widely used in treating hyperprolactinemia (hyperPRL) as a kind of Chinese traditional herb in China. In this study, we investigated the anti-hyperPRL activity of water extract of Fructus Hordei Germinatus (WEFHG) and mechanism of action. Methods. Effect of WEFHG on serum prolactin (PRL), estradiol (E2), progesterone (P), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and hypothalamus protein kinase A (PKA) and cyclic adenosine monophosphate (cAMP) levels of hyperPRL rats were investigated. And effect of WEFHG on PRL secretion, D2 receptors, and dopamine transporters (DAT) was studied in MMQ, GH3, and PC12 cells, respectively. Results. WEFHG reduced the secretion of PRL in hyperPRL rats effectively. In MMQ cell, treatment with WEFHG at 1–5 mg/mL significantly suppressed PRL secretion and synthesis. Consistent with a D2-action, WEFHG did not affect PRL in rat pituitary lactotropic tumor-derived GH3 cells that lack the D2 receptor expression but significantly increased the expression of D2 receptors and DAT in PC12 cells. In addition, WEFHG reduced the cAMP and PKA levels of hypothalamus in hyperPRL rats significantly. Conclusions. WEFHG showed anti-hyperPRL activity via dopamine D2 receptor, which was related to the second messenger cAMP and PKA. PMID:25254056

  1. Central D2 receptor occupancy and effects of zuclopenthixol acetate in humans.

    PubMed

    Nyberg, S; Farde, L; Bartfai, A; Halldin, C

    1995-11-01

    Repeated positron emission tomography (PET) measurements of D2 receptor occupancy, plasma concentrations of zuclopenthixol and reaction time were performed in three healthy subjects after injection of 12.5 mg zuclopenthixol acetate (ZPTA) in an open study design. Five control subjects were examined for reaction time only. D2 receptor occupancy was 51%, 71% and 75% after 7 h and 75%, 83% and 87% after 31 h in the three subjects. The subjects reported sedation, but reaction time was not prolonged. After the low dose of 12.5 mg ZPTA, D2 receptor occupancy exceeded the 70% assumed to be required to induce antipsychotic effect. Extrapolation of data to a clinical dose interval indicates that 50-150 mg ZPTA should induce very high D2 receptor occupancy lasting several days after injection. Such high doses may be required to induce sedation and to avoid frequent intramuscular injections in acutely psychotic patients. However, the simultaneously induced very high D2 receptor occupancy calls for careful assessment of acute extrapyramidal symptoms.

  2. Diagnostic utility of Fli-1 and D2-40 in distinguishing atypical fibroxanthoma from angiosarcoma.

    PubMed

    Cuda, Jonathan; Mirzamani, Neda; Kantipudi, Ramya; Robbins, Jason; Welsch, Micheal Jude; Sundram, Uma N

    2013-05-01

    Although in most cases one can easily distinguish between atypical fibroxanthomas and angiosarcomas, hemorrhagic atypical fibroxanthomas can pose a diagnostic problem. In rare cases, the large atypical cells of atypical fibroxanthoma can stain with CD31, leading to the erroneous diagnosis of angiosarcoma. We elected to further study this conundrum with 2 additional markers of lymphatic and vascular elements, namely D2-40 (podoplanin) and Fli-1, respectively. We studied 26 cases of atypical fibroxanthoma and 20 cases of angiosarcoma with Fli-1 and D2-40. We found that both Fli-1 and D2-40 stained a majority of cases of angiosarcoma (16/20 and 12/20, respectively), although only staining a minority of cases of atypical fibroxanthoma (8/26 for both). In addition, D2-40 staining of atypical fibroxanthoma was usually weak when positive, whereas Fli-1 staining of angiosarcomas was mostly strong and nuclear. Thus, both D2-40 and Fli-1 seem to be useful in distinguishing between atypical fibroxanthomas and angiosarcomas.

  3. Reactivity of Fe-0 atoms and clusters with D2O over FeO(111)

    SciTech Connect

    Parkinson, Gareth S.; Kim, Yu K.; Dohnalek, Zdenek; Smith, R. Scott; Kay, Bruce D.

    2009-03-26

    The interaction of Fe0 atoms with D2O layers on FeO(111) has been investigated using the “atom dropping” preparation technique and a combination of temperature programmed desorption, x-ray photoelectron spectroscopy, Auger electron spectroscopy, and infrared absorption spectroscopy. The data demonstrate that isolated Fe atoms form DFeOD insertion species upon deposition at 35 K, which then dissociate into FeOD and a surface hydroxyl above 200 K. Interestingly, even at very low Fe0 coverages the D2O is perturbed by the presence of the Fe, but only D2O desorption is observed. At higher (≥ 0.5 ML) coverages, clusters of Fe form which have molecular D2O and OD species adsorbed on the surface. Both molecular and recombinative desorption are observed in TPD. In contrast to the low coverage data, a second reaction pathway emerges at high coverage which leads to desorption of D2 and the formation of stable substoichiometric oxide. The mechanism for this minor channel is concluded to involve a reaction between two (or more) DFeOD complexes.

  4. Pigment stoichiometry of a newly isolated D1-D2-Cyt b559 complex from the higher plant Beta vulgaris L.

    PubMed

    Montoya, G; Yruela, I; Picorel, R

    1991-06-03

    Two D1-D2-Cyt b559 complexes with different pigment stoichiometry were isolated from the higher plant B. vulgaris. The procedures for isolating both complexes only differed in the washing time of the DEAE column with 50 mM Tris-HCl, pH 7.2, 0.05% Triton X-100 and 30 mM NaCl. When the column was washed until the eluate had an absorbance of 0.01 at 670 nm, the isolated D1-D2-Cyt b559 complex presented a pigment stoichiometry of 6 chlorophyll a, 2 beta-carotene, and 1 cytochrome b559 per 2 pheophytin a. In contrast, when the column was exhaustively washed until the eluate reached an absorbance of 0.005 at 670 nm, the complex had a stoichiometry of 4 chlorophyll a, 1 beta-carotene, and 1 cytochrome b559 per 2 pheophytin a. We think that the former stoichiometry corresponds to that of the native D1-D2-Cyt b559 complex. Moreover, both preparations showed 2 mol of pheophytin a per 1 mol of reaction center protein.

  5. Quantitative Analysis of D2 Dopamine Receptor Binding in the Living Human Brain by PET

    NASA Astrophysics Data System (ADS)

    Farde, Lars; Hall, Hakan; Ehrin, Erling; Sedvall, Goran

    1986-01-01

    D2 dopamine receptors in the putamen of living human subjects were characterized by using the selective, high-affinity D2 dopamine receptor antagonist carbon-11-labeled raclopride and positron emission tomography. Experiments in four healthy men demonstrated saturability of [11C]raclopride binding to an apparently homogeneous population of sites with Hill coefficients close to unity. In the normal putamen, maximum binding ranged from 12 to 17 picomoles per cubic centimeter and dissociation constants from 3.4 to 4.7 nanomolar. Maximum binding for human putamen at autopsy was 15 picomoles per cubic centimeter. Studies of [11C]raclopride binding indicate that clinically effective doses of chemically distinct neuroleptic drugs result in 85 to 90 percent occupancy of D2 dopamine receptors in the putamen of schizophrenic patients.

  6. Spectroscopic investigation of the 3d 2D → nf 2F transitions in lithium

    NASA Astrophysics Data System (ADS)

    Shahzada, S.; Shah, M.; Haq, S. U.; Nawaz, M.; Ahmed, M.; Nadeem, Ali

    2016-05-01

    We report term energies and effective quantum numbers of the odd parity 3d 2D → nf 2F series of lithium using multi-step and multi-photon laser excitation schemes. The experiments were performed using three dye lasers simultaneously pumped by the second harmonic (532 nm) of a Q-switched Nd:YAG laser in conjunction with an atomic beam apparatus and thermionic diode ion detector. The first ionization potential of lithium has been determined as 43,487.13 ± 0.02 cm- 1 from the much extended 3d 2D → nf 2F (17 ≤ n ≤ 70) series. In addition, the oscillator strengths of the 3d 2D → nf 2F (15 ≤ n ≤ 48) transitions have been determined, showing a decreasing trend with the increase in principal quantum number n.

  7. Suppressive effect of the dopamine D2 receptor agonist B-HT 920 on rat grooming.

    PubMed

    Ferrari, F; Pelloni, F; Giuliani, D

    1992-06-17

    The effect of the D2 agonist B-HT 920 was examined on three behavioural models of induced grooming in the rat. B-HT 920 potently inhibited the grooming elicited by a novel environment, whereas it stimulated the stretching-yawning syndrome. Pretreatment with the selective dopamine D2 receptor antagonist, sulpiride, reversed the phenomenon. When B-HT 920 was administered to rats before water immersion, it similarly antagonized total grooming; wet-dog shakes, detected in these same animals, were potently inhibited. Finally, B-HT 920 displayed inhibitory activity towards adrenocorticotropin hormone-induced excessive grooming. On the basis of these effects, the role of D2 receptor subtypes in the modulation of grooming is discussed.

  8. The infrared spectrum of the Ar-C2D2 complex

    NASA Astrophysics Data System (ADS)

    Rezaei, M.; McKellar, A. R. W.; Moazzen-Ahmadi, N.

    2016-10-01

    Infrared spectra of Ar-C2D2 are observed in the region of the ν3 fundamental band (asymmetric C-D stretch, ≈2440 cm-1) using a tunable optical parametric oscillator to probe a pulsed supersonic slit jet expansion from a cooled nozzle. Transitions are assigned involving K = 0-2 in the ground vibrational state, and K = 0-4 in the excited state. The intermolecular bending combination band is also observed, giving a bending frequency of 4.798 cm-1. Despite this low bending frequency, the Ar-C2D2 spectrum qualitatively resembles that of a normal semi-rigid molecule, in contrast to He- and Ne-C2D2 which are much closer to the limit of free internal rotation.

  9. D2-like dopamine receptors mediate the response to amphetamine in a mouse model of ADHD

    PubMed Central

    Fan, Xueliang; Hess, Ellen J.

    2007-01-01

    The mechanisms underlying the effects of psychostimulants in attention deficit hyperactivity disorder (ADHD) are not well understood, but indirect evidence implicates D2 dopamine receptors. Here we dissect the components of dopaminergic neurotransmission in the hyperactive mouse mutant coloboma to identify pre- and postsynaptic elements essential for the effects of amphetamine in these mice. Amphetamine treatment reduced locomotor activity in coloboma mice, but induced a robust increase in dopamine overflow suggesting that abnormal regulation of dopamine efflux does not account for the behavioral effect. However, the D2-like dopamine receptor antagonists haloperidol and raclopride, but not the D1-like dopamine receptor antagonist SCH23390, blocked the amphetamine-induced reduction in locomotor activity in coloboma mice, providing direct evidence that D2-like dopamine receptors mediate the effect of amphetamine in these mice. With the precedent established that it is possible to directly antagonize this response, this strategy should prove useful for identifying novel therapeutics in ADHD. PMID:17291774

  10. Presence of dopamine D-2 receptors in human tumoral cell lines

    SciTech Connect

    Sokoloff, P.; Riou, J.F.; Martres, M.P.; Schwartz, J.C. )

    1989-07-31

    ({sup 125}I) Iodosulpride binding was examined on eight human cell lines derived from lung, breast and digestive tract carcinomas, neuroblastomas and leukemia. Specific binding was detected in five of these cell lines. In the richest cell line N417, derived from small cell lung carcinoma, ({sup 125}I) iodosulpride bound with a high affinity (Kd = 1.3 nM) to an apparently homogeneous population of binding site (Bmax = 1,606 sites per cell). These sites displayed a typical D-2 specificity, established with several dopaminergic agonists and antagonists selective of either D-1 or D-2 receptor subtypes. In addition, dopamine, apomorphine and RU 24926 distinguished high- and low-affinity sites, suggesting that the binding sites are associated with a G-protein. The biological significance and the possible diagnostic implication of the presence of D-2 receptors on these cell lines are discussed.

  11. 26 CFR 1.674(d)-2 - Limitations on exceptions in section 674 (b), (c), and (d).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Limitations on exceptions in section 674 (b), (c), and (d). 1.674(d)-2 Section 1.674(d)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... § 1.674(d)-2 Limitations on exceptions in section 674 (b), (c), and (d). (a) Power to remove...

  12. 26 CFR 1.674(d)-2 - Limitations on exceptions in section 674 (b), (c), and (d).

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 8 2011-04-01 2011-04-01 false Limitations on exceptions in section 674 (b), (c), and (d). 1.674(d)-2 Section 1.674(d)-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE... Substantial Owners § 1.674(d)-2 Limitations on exceptions in section 674 (b), (c), and (d). (a) Power...

  13. Hyperdopaminergic Tone Erodes Prefrontal LTP via a D2 Receptor-operated Protein Phosphatase Gate

    PubMed Central

    Xu, Tai-Xiang; Sotnikova, Tatyana D.; Liang, Chengyu; Zhang, Jingping; Jung, Jae U.; Spealman, Roger D.; Gainetdinov, Raul R.; Yao, Wei-Dong

    2009-01-01

    Dopamine (DA) plays crucial roles in the cognitive functioning of the prefrontal cortex (PFC), which, to a large degree, depends on lasting neural traces formed in prefrontal networks. The establishment of these permanent traces requires changes in cortical synaptic efficacy. DA, via the D1-class receptors, is thought to gate or facilitate synaptic plasticity in the PFC, with little role recognized for the D2-class receptors. Here we show that, when significantly elevated, DA erodes, rather than facilitates, the induction of long-term potentiation (LTP) in the PFC by acting at the far less abundant cortical D2-class receptors through a dominant coupling to the protein phosphatase 1 (PP1) activity in postsynaptic neurons. In mice with persistently elevated extracellular DA, resulting from inactivation of the DA transporter (DAT) gene, LTP in layer V PFC pyramidal neurons can not be established, regardless of induction protocols. Acute increase of dopaminergic transmission by DAT blockers or overstimulation of D2 receptors in normal mice have similar LTP shut-off effects. LTP in mutant mice can be rescued by a single in vivo administration of D2-class antagonists. Suppression of postsynaptic PP1 mimics and occludes the D2-mediated rescue of LTP in mutant mice, and prevents the acute erosion of LTP by D2 agonists in normal mice. Our studies reveal a mechanistically unique heterosynaptic PP1 gate that is constitutively driven by background DA to influence LTP induction. By blocking prefrontal synaptic plasticity, excessive DA may prevent storage of lasting memory traces in PFC networks and impair executive functions. PMID:19906957

  14. R2d2 Drives Selfish Sweeps in the House Mouse.

    PubMed

    Didion, John P; Morgan, Andrew P; Yadgary, Liran; Bell, Timothy A; McMullan, Rachel C; Ortiz de Solorzano, Lydia; Britton-Davidian, Janice; Bult, Carol J; Campbell, Karl J; Castiglia, Riccardo; Ching, Yung-Hao; Chunco, Amanda J; Crowley, James J; Chesler, Elissa J; Förster, Daniel W; French, John E; Gabriel, Sofia I; Gatti, Daniel M; Garland, Theodore; Giagia-Athanasopoulou, Eva B; Giménez, Mabel D; Grize, Sofia A; Gündüz, İslam; Holmes, Andrew; Hauffe, Heidi C; Herman, Jeremy S; Holt, James M; Hua, Kunjie; Jolley, Wesley J; Lindholm, Anna K; López-Fuster, María J; Mitsainas, George; da Luz Mathias, Maria; McMillan, Leonard; Ramalhinho, Maria da Graça Morgado; Rehermann, Barbara; Rosshart, Stephan P; Searle, Jeremy B; Shiao, Meng-Shin; Solano, Emanuela; Svenson, Karen L; Thomas-Laemont, Patricia; Threadgill, David W; Ventura, Jacint; Weinstock, George M; Pomp, Daniel; Churchill, Gary A; Pardo-Manuel de Villena, Fernando

    2016-06-01

    A selective sweep is the result of strong positive selection driving newly occurring or standing genetic variants to fixation, and can dramatically alter the pattern and distribution of allelic diversity in a population. Population-level sequencing data have enabled discoveries of selective sweeps associated with genes involved in recent adaptations in many species. In contrast, much debate but little evidence addresses whether "selfish" genes are capable of fixation-thereby leaving signatures identical to classical selective sweeps-despite being neutral or deleterious to organismal fitness. We previously described R2d2, a large copy-number variant that causes nonrandom segregation of mouse Chromosome 2 in females due to meiotic drive. Here we show population-genetic data consistent with a selfish sweep driven by alleles of R2d2 with high copy number (R2d2(HC)) in natural populations. We replicate this finding in multiple closed breeding populations from six outbred backgrounds segregating for R2d2 alleles. We find that R2d2(HC) rapidly increases in frequency, and in most cases becomes fixed in significantly fewer generations than can be explained by genetic drift. R2d2(HC) is also associated with significantly reduced litter sizes in heterozygous mothers, making it a true selfish allele. Our data provide direct evidence of populations actively undergoing selfish sweeps, and demonstrate that meiotic drive can rapidly alter the genomic landscape in favor of mutations with neutral or even negative effects on overall Darwinian fitness. Further study will reveal the incidence of selfish sweeps, and will elucidate the relative contributions of selfish genes, adaptation and genetic drift to evolution.

  15. R2d2 Drives Selfish Sweeps in the House Mouse

    PubMed Central

    Didion, John P.; Morgan, Andrew P.; Yadgary, Liran; Bell, Timothy A.; McMullan, Rachel C.; Ortiz de Solorzano, Lydia; Britton-Davidian, Janice; Bult, Carol J.; Campbell, Karl J.; Castiglia, Riccardo; Ching, Yung-Hao; Chunco, Amanda J.; Crowley, James J.; Chesler, Elissa J.; Förster, Daniel W.; French, John E.; Gabriel, Sofia I.; Gatti, Daniel M.; Garland, Theodore; Giagia-Athanasopoulou, Eva B.; Giménez, Mabel D.; Grize, Sofia A.; Gündüz, İslam; Holmes, Andrew; Hauffe, Heidi C.; Herman, Jeremy S.; Holt, James M.; Hua, Kunjie; Jolley, Wesley J.; Lindholm, Anna K.; López-Fuster, María J.; Mitsainas, George; da Luz Mathias, Maria; McMillan, Leonard; Ramalhinho, Maria da Graça Morgado; Rehermann, Barbara; Rosshart, Stephan P.; Searle, Jeremy B.; Shiao, Meng-Shin; Solano, Emanuela; Svenson, Karen L.; Thomas-Laemont, Patricia; Threadgill, David W.; Ventura, Jacint; Weinstock, George M.; Pomp, Daniel; Churchill, Gary A.; Pardo-Manuel de Villena, Fernando

    2016-01-01

    A selective sweep is the result of strong positive selection driving newly occurring or standing genetic variants to fixation, and can dramatically alter the pattern and distribution of allelic diversity in a population. Population-level sequencing data have enabled discoveries of selective sweeps associated with genes involved in recent adaptations in many species. In contrast, much debate but little evidence addresses whether “selfish” genes are capable of fixation—thereby leaving signatures identical to classical selective sweeps—despite being neutral or deleterious to organismal fitness. We previously described R2d2, a large copy-number variant that causes nonrandom segregation of mouse Chromosome 2 in females due to meiotic drive. Here we show population-genetic data consistent with a selfish sweep driven by alleles of R2d2 with high copy number (R2d2HC) in natural populations. We replicate this finding in multiple closed breeding populations from six outbred backgrounds segregating for R2d2 alleles. We find that R2d2HC rapidly increases in frequency, and in most cases becomes fixed in significantly fewer generations than can be explained by genetic drift. R2d2HC is also associated with significantly reduced litter sizes in heterozygous mothers, making it a true selfish allele. Our data provide direct evidence of populations actively undergoing selfish sweeps, and demonstrate that meiotic drive can rapidly alter the genomic landscape in favor of mutations with neutral or even negative effects on overall Darwinian fitness. Further study will reveal the incidence of selfish sweeps, and will elucidate the relative contributions of selfish genes, adaptation and genetic drift to evolution. PMID:26882987

  16. Interaction of the Agrobacterium tumefaciens virulence protein VirD2 with histones.

    PubMed

    Wolterink-van Loo, Suzanne; Escamilla Ayala, Abril A; Hooykaas, Paul J J; van Heusden, G Paul H

    2015-02-01

    Agrobacterium tumefaciens is a Gram-negative soil bacterium that genetically transforms plants and, under laboratory conditions, also transforms non-plant organisms, such as fungi and yeasts. During the transformation process a piece of ssDNA (T-strand) is transferred into the host cells via a type IV secretion system. The VirD2 relaxase protein, which is covalently attached at the 5' end of the T-strand through Tyr29, mediates nuclear entry as it contains a nuclear localization sequence. How the T-strand reaches the chromatin and becomes integrated in the chromosomal DNA is still far from clear. Here, we investigated whether VirD2 binds to histone proteins in the yeast Saccharomyces cerevisiae. Using immobilized GFP-VirD2 and in vitro synthesized His6-tagged S. cerevisiae proteins, interactions between VirD2 and the histones H2A, H2B, H3 and H4 were revealed. In vivo, these interactions were confirmed by bimolecular fluorescence complementation experiments. After co-cultivation of Agrobacterium strains expressing VirD2 tagged with a fragment of the yellow fluorescent protein analogue Venus with yeast strains expressing histone H2A or H2B tagged with the complementary part of Venus, fluorescence was detected in dot-shaped structures in the recipient yeast cells. The results indicated that VirD2 was transferred from Agrobacterium to yeast cells and that it interacted with histones in the host cell, and thus may help direct the T-DNA (transferred DNA) to the chromatin as a prelude to integration into the host chromosomal DNA.

  17. Effects of vitamin D2-fortified bread v. supplementation with vitamin D2 or D3 on serum 25-hydroxyvitamin D metabolites: an 8-week randomised-controlled trial in young adult Finnish women.

    PubMed

    Itkonen, Suvi T; Skaffari, Essi; Saaristo, Pilvi; Saarnio, Elisa M; Erkkola, Maijaliisa; Jakobsen, Jette; Cashman, Kevin D; Lamberg-Allardt, Christel

    2016-04-14

    There is a need for food-based solutions for preventing vitamin D deficiency. Vitamin D3 (D3) is mainly used in fortified food products, although the production of vitamin D2 (D2) is more cost-effective, and thus may hold opportunities. We investigated the bioavailability of D2 from UV-irradiated yeast present in bread in an 8-week randomised-controlled trial in healthy 20-37-year-old women (n 33) in Helsinki (60°N) during winter (February-April) 2014. Four study groups were given different study products (placebo pill and regular bread=0 µg D2 or D3/d; D2 supplement and regular bread=25 µg D2/d; D3 supplement and regular bread=25 µg D3/d; and placebo pill and D2-biofortified bread=25 µg D2/d). Serum 25-hydroxyvitamin D2 (S-25(OH)D2) and serum 25-hydroxyvitamin D3 (S-25(OH)D3) concentrations were measured at baseline, midpoint and end point. The mean baseline total serum 25-hydroxyvitamin D (S-25(OH)D=S-25(OH)D2+S-25(OH)D3) concentration was 65·1 nmol/l. In repeated-measures ANCOVA (adjusted for baseline S-25(OH)D as total/D2/D3), D2-bread did not affect total S-25(OH)D (P=0·707) or S-25(OH)D3 (P=0·490), but increased S-25(OH)D2 compared with placebo (P<0·001). However, the D2 supplement was more effective than bread in increasing S-25(OH)D2 (P<0·001). Both D2 and D3 supplementation increased total S-25(OH)D compared with placebo (P=0·030 and P=0·001, respectively), but D2 supplementation resulted in lower S-25(OH)D3 (P<0·001). Thus, D2 from UV-irradiated yeast in bread was not bioavailable in humans. Our results support the evidence that D2 is less potent in increasing total S-25(OH)D concentrations than D3, also indicating a decrease in the percentage contribution of S-25(OH)D3 to the total vitamin D pool.

  18. Adolescent Maturation of Dopamine D1 and D2 Receptor Function and Interactions in Rodents

    PubMed Central

    Dwyer, Jennifer B.; Leslie, Frances M.

    2016-01-01

    Adolescence is a developmental period characterized by heightened vulnerability to illicit drug use and the onset of neuropsychiatric disorders. These clinical phenomena likely share common neurobiological substrates, as mesocorticolimbic dopamine systems actively mature during this period. Whereas prior studies have examined age-dependent changes in dopamine receptor binding, there have been fewer functional analyses. The aim of the present study was therefore to determine whether the functional consequences of D1 and D2-like activation are age-dependent. Adolescent and adult rats were given direct D1 and D2 agonists, alone and in combination. Locomotor and stereotypic behaviors were measured, and brains were collected for analysis of mRNA expression for the immediate early genes (IEGs), cfos and arc. Adolescents showed enhanced D2-like receptor control of locomotor and repetitive behaviors, which transitioned to dominant D1-like mechanisms in adulthood. When low doses of agonists were co-administered, adults showed supra-additive behavioral responses to D1/D2 combinations, whereas adolescents did not, which may suggest age differences in D1/D2 synergy. D1/D2-stimulated IEG expression was particularly prominent in the bed nucleus of the stria terminalis (BNST). Given the BNST’s function as an integrator of corticostriatal, hippocampal, and stress-related circuitry, and the importance of neural network dynamics in producing behavior, an exploratory functional network analysis of regional IEG expression was performed. This data-driven analysis demonstrated similar developmental trajectories as those described in humans and suggested that dopaminergic drugs alter forebrain coordinated gene expression age dependently. D1/D2 recruitment of stress nuclei into functional networks was associated with low behavioral output in adolescents. Network analysis presents a novel tool to assess pharmacological action, and highlights critical developmental changes in functional

  19. Rovibrational product state distribution for inelastic H+D2 collisions.

    PubMed

    Pomerantz, Andrew E; Ausfelder, Florian; Zare, Richard N; Juanes-Marcos, Juan Carlos; Althorpe, Stuart C; Sáez Rábanos, V; Aoiz, F J; Bañares, L; Castillo, J F

    2004-10-08

    Experimental measurements of rovibrational product state distributions for the inelastic scattering process H + D2(nu=0,j)-->H + D2(nu' = 1,2,j') are presented and compared with the results of quasiclassical and quantum mechanical calculations. Agreement between theory and experiment is almost quantitative. Two subtle trends are found: the relative amount of energy in product rotational excitation decreases slightly with increasing collision energy and increases slightly with increasing product vibrational excitation. These trends are the reverse of what has been found for reactive scattering in which the opposite trends are much more pronounced.

  20. Glory and thresholds effects in H+D 2 reactive angular scattering

    NASA Astrophysics Data System (ADS)

    Sokolovski, D.

    2003-03-01

    We analyse H+D 2 reactive angular scattering using the S-matrix elements obtained by Aoiz et al. and Althorpe et al. Enhancement of small angle scattering in the v'=3← v=0 H+D 2 delayed reaction is attributed to a glory effect caused by threshold resonances in the v=3 vibrationally adiabatic channel. The oscillatory structures in the reactive angular distributions are shown to be of nearside-farside (NP) origin and are likely to arise from capture in a number of relatively short-lived barrier Regge states at large angular momenta. Padé reconstruction of the reactive matrix element is discussed in detail.

  1. A review of 3D/2D registration methods for image-guided interventions.

    PubMed

    Markelj, P; Tomaževič, D; Likar, B; Pernuš, F

    2012-04-01

    Registration of pre- and intra-interventional data is one of the key technologies for image-guided radiation therapy, radiosurgery, minimally invasive surgery, endoscopy, and interventional radiology. In this paper, we survey those 3D/2D data registration methods that utilize 3D computer tomography or magnetic resonance images as the pre-interventional data and 2D X-ray projection images as the intra-interventional data. The 3D/2D registration methods are reviewed with respect to image modality, image dimensionality, registration basis, geometric transformation, user interaction, optimization procedure, subject, and object of registration.

  2. DOPEX-1D2C: A one-dimensional, two-constraint radiation shield optimization code

    NASA Technical Reports Server (NTRS)

    Lahti, G. P.

    1973-01-01

    A one-dimensional, two-constraint radiation sheild weight optimization procedure and a computer program, DOPEX-1D2C, is described. The DOPEX-1D2C uses the steepest descent method to alter a set of initial (input) thicknesses of a spherical shield configuration to achieve a minimum weight while simultaneously satisfying two dose-rate constraints. The code assumes an exponential dose-shield thickness relation with parameters specified by the user. Code input instruction, a FORTRAN-4 listing, and a sample problem are given. Typical computer time required to optimize a seven-layer shield is less than 1/2 minute on an IBM 7094.

  3. Plasma 25-hydroxyvitamin D2 and D3 levels and incidence of postoperative atrial fibrillation.

    PubMed

    Skuladottir, G V; Cohen, A; Arnar, D O; Hougaard, D M; Torfason, B; Palsson, R; Indridason, O S

    2016-01-01

    Low circulating levels of total 25-hydroxyvitamin D (25(OH)D) have been associated with an increased risk of adverse effects after cardiac surgery. The metabolites, 25(OH)D2 and 25(OH)D3, provide a good index of vitamin D status. In this study, we examined the association between preoperative plasma levels of total 25(OH)D, 25(OH)D2 and 25(OH)D3 and the risk of postoperative atrial fibrillation (POAF) following open heart surgery. The levels of plasma 25(OH)D2 and 25(OH)D3 in 118 patients, who underwent coronary artery bypass grafting and/or valvular surgery, were measured immediately prior to surgery and on postoperative day 3 by liquid chromatography-tandem mass spectrometry. Patients who developed POAF had higher median plasma levels of 25(OH)D2 than those who remained in sinus rhythm (SR) (P = 0·003), but no significant difference was noted in levels of 25(OH)D3 or total 25(OH)D between the two groups (P > 0·05). By univariate analysis, patients with total 25(OH)D and 25(OH)D2 levels above the median had higher frequency of POAF (P < 0·05) and the incidence of POAF increased significantly with each higher quartile of preoperative plasma levels of 25(OH)D2 (P = 0·001), an association that was independent of confounding factors. In both the SR and POAF groups, the median plasma levels of 25(OH)D2, 25(OH)D3 and total 25(OH)D were lower (P < 0·05) on the third postoperative day compared with preoperatively. Our findings demonstrate that higher plasma levels of 25(OH)D2 are associated with increased risk of POAF, while this is not the case for 25(OH)D3 or total 25(OH)D. The reason for these discrepant results is not clear but warrants further study.

  4. STS-55 crewmembers work in the SL-D2 module onboard OV-102

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Working in the shirt-sleeve research environment of the Spacelab Deutsche 2 (SL-D2) science module are STS-55 Mission Specialist 1 (MS1) and Payload Commander (PLC) Jerry L. Ross, MS3 Bernard A. Harris, Jr, German Payload Specialist 2 Hans Schlegel, and German Payload Specialist 1 Ulrich Walter. Ross examines sample tube at Rack 8 Werkstofflabor (WL) (left). Harris, holding his arm, waits to have his blood drawn by Schlegel (right). Wearing the baroreflex (BA) collar at Rack 12 Experiment Rack and waving is Walter. The SL-D2 module is located in the payload bay (PLB) of the Earth-orbiting Columbia, Orbiter Vehicle (OV) 102.

  5. D1-D2 Dopamine Receptor Synergy Promotes Calcium Signaling via Multiple Mechanisms

    PubMed Central

    Chun, Lani S.; Free, R. Benjamin; Doyle, Trevor B.; Huang, Xi-Ping; Rankin, Michele L.

    2013-01-01

    The D1 dopamine receptor (D1R) has been proposed to form a hetero-oligomer with the D2 dopamine receptor (D2R), which in turn results in a complex that couples to phospholipase C–mediated intracellular calcium release. We have sought to elucidate the pharmacology and mechanism of action of this putative signaling pathway. Dopamine dose-response curves assaying intracellular calcium mobilization in cells heterologously expressing the D1 and D2 subtypes, either alone or in combination, and using subtype selective ligands revealed that concurrent stimulation is required for coupling. Surprisingly, characterization of a putative D1-D2 heteromer-selective ligand, 6-chloro-2,3,4,5-tetrahydro-3-methyl-1-(3-methylphenyl)-1H-3-benzazepine-7,8-diol (SKF83959), found no stimulation of calcium release, but it did find a broad range of cross-reactivity with other G protein–coupled receptors. In contrast, SKF83959 appeared to be an antagonist of calcium mobilization. Overexpression of Gqα with the D1 and D2 dopamine receptors enhanced the dopamine-stimulated calcium response. However, this was also observed in cells expressing Gqα with only the D1R. Inactivation of Gi or Gs with pertussis or cholera toxin, respectively, largely, but not entirely, reduced the calcium response in D1R and D2R cotransfected cells. Moreover, sequestration of Gβγ subunits through overexpression of G protein receptor kinase 2 mutants either completely or largely eliminated dopamine-stimulated calcium mobilization. Our data suggest that the mechanism of D1R/D2R–mediated calcium signaling involves more than receptor-mediated Gq protein activation, may largely involve downstream signaling pathways, and may not be completely heteromer-specific. In addition, SKF83959 may not exhibit selective activation of D1-D2 heteromers, and its significant cross-reactivity to other receptors warrants careful interpretation of its use in vivo. PMID:23680635

  6. Examining the Effects of Sodium Ions on the Binding of Antagonists to Dopamine D2 and D3 Receptors

    PubMed Central

    Wood, Martyn D.; Strange, Philip G.

    2016-01-01

    Many G protein-coupled receptors have been shown to be sensitive to the presence of sodium ions (Na+). Using radioligand competition binding assays, we have examined and compared the effects of sodium ions on the binding affinities of a number of structurally diverse ligands at human dopamine D2 and dopamine D3 receptor subtypes, which are important therapeutic targets for the treatment of psychotic disorders. At both receptors, the binding affinities of the antagonists/inverse agonists SB-277011-A, L,741,626, GR 103691 and U 99194 were higher in the presence of sodium ions compared to those measured in the presence of the organic cation, N-methyl-D-glucamine, used to control for ionic strength. Conversely, the affinities of spiperone and (+)-butaclamol were unaffected by the presence of sodium ions. Interestingly, the binding of the antagonist/inverse agonist clozapine was affected by changes in ionic strength of the buffer used rather than the presence of specific cations. Similar sensitivities to sodium ions were seen at both receptors, suggesting parallel effects of sodium ion interactions on receptor conformation. However, no clear correlation between ligand characteristics, such as subtype selectivity, and sodium ion sensitivity were observed. Therefore, the properties which determine this sensitivity remain unclear. However these findings do highlight the importance of careful consideration of assay buffer composition for in vitro assays and when comparing data from different studies, and may indicate a further level of control for ligand binding in vivo. PMID:27379794

  7. Dorsal striatal D2-like receptor availability covaries with sensitivity to positive reinforcement during discrimination learning.

    PubMed

    Groman, Stephanie M; Lee, Buyean; London, Edythe D; Mandelkern, Mark A; James, Alex S; Feiler, Karen; Rivera, Ronald; Dahlbom, Magnus; Sossi, Vesna; Vandervoort, Eric; Jentsch, J David

    2011-05-18

    Deviations in reward sensitivity and behavioral flexibility, particularly in the ability to change or stop behaviors in response to changing environmental contingencies, are important phenotypic dimensions of several neuropsychiatric disorders. Neuroimaging evidence suggests that variation in dopamine signaling through dopamine D(2)-like receptors may influence these phenotypes, as well as associated psychiatric conditions, but the specific neurocognitive mechanisms through which this influence is exerted are unknown. To address this question, we examined the relationship between behavioral sensitivity to reinforcement during discrimination learning and D(2)-like receptor availability in vervet monkeys. Monkeys were assessed for their ability to acquire, retain, and reverse three-choice, visual-discrimination problems, and once behavioral performance had stabilized, they received positron emission tomography (PET) scans. D(2)-like receptor availability in dorsal aspects of the striatum was not related to individual differences in the ability to acquire or retain visual discriminations but did relate to the number of trials required to reach criterion in the reversal phase of the task. D(2)-like receptor availability was also strongly correlated with behavioral sensitivity to positive, but not negative, feedback during learning. These results go beyond electrophysiological findings by demonstrating the involvement of a striatal dopaminergic marker in individual differences in feedback sensitivity and behavioral flexibility, providing insight into the neural mechanisms that are affected in neuropsychiatric disorders that feature these deficits.

  8. Solid H2 and D2: Remarkable differences in some NMR properties

    NASA Astrophysics Data System (ADS)

    Harris, A. B.; Meyer, H.; Qin, X.

    1994-02-01

    The differences in the observed properties of solid H2 and D2 are reviewed, and in particular those encountered in NMR experiments. The failure to detect a sharp NMR (I=1) impurity ``isolated pair'' spectrum in p-D2 is discussed in terms of a larger crystalline field than in H2, where an intense and sharp pair spectrum has been observed. Furthermore, we discuss the dramatic (I=1) solid echo signal loss with decreasing temperature which is observed in solid D2, but not for solid H2. A theory of the solid echo damping through orientational fluctuations is developed. This theory accounts for the observed solid echo decay in D2 as a function of the pulse spacing time τ and leads to an estimation of the order parameter fluctuation amplitude and the correlation time τc. However, the theory cannot account for the loss of spin (as determined from Curie's law), which must occur for very small values of τ that are not covered by the theory.

  9. Official portrait of STS-55 SL-D2 Payload Specialist 1 Ulrich Walter

    NASA Technical Reports Server (NTRS)

    1993-01-01

    German Payload Specialist 1 Ulrich Walter poses for his Official portrait. Walter is assigned to the STS-55 Columbia, Orbiter Vehicle (OV) 102, Spacelab Deutsche 2 (SL-D2) mission. This is the second dedicated German Spacelab flight. United States and German flags and a space shuttle orbiter model in launch configuration create the backdrop.

  10. Cold brittleness of corrosion-resistant maraging steel 08Kh15N5D2T

    NASA Astrophysics Data System (ADS)

    Makhneva, T. M.

    2012-03-01

    Results of a study of the effect of the method of remelting and of heat treatment modes on the behavior of serial curves of impact toughness and on the position of cold-shortness threshold in steel 08Kh15N5D2T are presented.

  11. Effects of sigma(1) receptor ligand MS-377 on D(2) antagonists-induced behaviors.

    PubMed

    Karasawa, Jun-ichi; Takahashi, Shinji; Takagi, Kaori; Horikomi, Kazutoshi

    2002-10-01

    (R)-(+)-1-(4-Chlorophenyl)-3-[4-(2-methoxyethyl)piperazin-1-yl]methyl-2-pyrrolidinone L-tartrate (MS-377) is a novel antipsychotic agent with selective and high affinity for sigma(1) receptor. The present study was carried out to clarify the interaction of MS-377 with dopamine D(2) receptor antagonists (D(2) antagonists) in concurrent administration, and then the involvement of sigma receptors in the interaction. The effects of MS-377 on haloperidol- or sultopride-induced inhibition of apomorphine-induced climbing behavior and catalepsy were investigated in mice and rats, respectively. In addition, the effects of (+)-SKF-10,047 and SA4503, both of which are sigma receptor agonists, and WAY-100,635, which is a 5-HT(1A) receptor antagonist, on the interaction due to the concurrent use were also investigated. MS-377 potentiated the inhibitory effects of haloperidol or sultopride on apomorphine-induced climbing behavior in a dose-dependent manner. In contrast, MS-377 did not affect the catalepsy induction by these drugs. The potentiation of the inhibitory effects of haloperidol or sultopride on apomorphine-induced climbing behavior by MS-377 was not inhibited by WAY-100,635, but was inhibited by (+)-SKF-10,047 and SA4503. These findings showed that MS-377 potentiates the efficacy of D(2) antagonists, but it does not deteriorate the adverse effect. Moreover, sigma(1) receptors are involved in this potentiation of the efficacy of D(2) antagonists by MS-377.

  12. Striatal dopamine D2-like receptor correlation patterns with human obesity and opportunistic eating behavior.

    PubMed

    Guo, J; Simmons, W K; Herscovitch, P; Martin, A; Hall, K D

    2014-10-01

    The obesity epidemic is believed to be driven by a food environment that promotes consumption of inexpensive, convenient, high-calorie, palatable foods. Individual differences in obesity susceptibility or resistance to weight loss may arise because of alterations in the neurocircuitry supporting food reward and eating habits. In particular, dopamine signaling in the ventromedial striatum is thought to encode food reward and motivation, whereas dopamine in the dorsal and lateral striatum orchestrates the development of eating habits. We measured striatal dopamine D2-like receptor binding potential (D2BP) using positron emission tomography with [(18)F]fallypride in 43 human subjects with body mass indices (BMI) ranging from 18 to 45 kg m(-)(2). Opportunistic eating behavior and BMI were both positively associated with D2BP in the dorsal and lateral striatum, whereas BMI was negatively associated with D2BP in the ventromedial striatum. These results suggest that obese people have alterations in dopamine neurocircuitry that may increase their susceptibility to opportunistic overeating while at the same time making food intake less rewarding, less goal directed and more habitual. Whether or not the observed neurocircuitry alterations pre-existed or occurred as a result of obesity development, they may perpetuate obesity given the omnipresence of palatable foods and their associated cues.

  13. Enhanced GABA Transmission Drives Bradykinesia Following Loss of Dopamine D2 Receptor Signaling.

    PubMed

    Lemos, Julia C; Friend, Danielle M; Kaplan, Alanna R; Shin, Jung Hoon; Rubinstein, Marcelo; Kravitz, Alexxai V; Alvarez, Veronica A

    2016-05-18

    Bradykinesia is a prominent phenotype of Parkinson's disease, depression, and other neurological conditions. Disruption of dopamine (DA) transmission plays an important role, but progress in understanding the exact mechanisms driving slowness of movement has been impeded due to the heterogeneity of DA receptor distribution on multiple cell types within the striatum. Here we show that selective deletion of DA D2 receptors (D2Rs) from indirect-pathway medium spiny neurons (iMSNs) is sufficient to impair locomotor activity, phenocopying DA depletion models of Parkinson's disease, despite this mouse model having intact DA transmission. There was a robust enhancement of GABAergic transmission and a reduction of in vivo firing in striatal and pallidal neurons. Mimicking D2R signaling in iMSNs with Gi-DREADDs restored the level of tonic GABAergic transmission and rescued the motor deficit. These findings indicate that DA, through D2R activation in iMSNs, regulates motor output by constraining the strength of GABAergic transmission.

  14. Tracking heavy water (D2O) incorporation for identifying and sorting active microbial cells.

    PubMed

    Berry, David; Mader, Esther; Lee, Tae Kwon; Woebken, Dagmar; Wang, Yun; Zhu, Di; Palatinszky, Marton; Schintlmeister, Arno; Schmid, Markus C; Hanson, Buck T; Shterzer, Naama; Mizrahi, Itzhak; Rauch, Isabella; Decker, Thomas; Bocklitz, Thomas; Popp, Jürgen; Gibson, Christopher M; Fowler, Patrick W; Huang, Wei E; Wagner, Michael

    2015-01-13

    Microbial communities are essential to the function of virtually all ecosystems and eukaryotes, including humans. However, it is still a major challenge to identify microbial cells active under natural conditions in complex systems. In this study, we developed a new method to identify and sort active microbes on the single-cell level in complex samples using stable isotope probing with heavy water (D2O) combined with Raman microspectroscopy. Incorporation of D2O-derived D into the biomass of autotrophic and heterotrophic bacteria and archaea could be unambiguously detected via C-D signature peaks in single-cell Raman spectra, and the obtained labeling pattern was confirmed by nanoscale-resolution secondary ion MS. In fast-growing Escherichia coli cells, label detection was already possible after 20 min. For functional analyses of microbial communities, the detection of D incorporation from D2O in individual microbial cells via Raman microspectroscopy can be directly combined with FISH for the identification of active microbes. Applying this approach to mouse cecal microbiota revealed that the host-compound foragers Akkermansia muciniphila and Bacteroides acidifaciens exhibited distinctive response patterns to amendments of mucin and sugars. By Raman-based cell sorting of active (deuterated) cells with optical tweezers and subsequent multiple displacement amplification and DNA sequencing, novel cecal microbes stimulated by mucin and/or glucosamine were identified, demonstrating the potential of the nondestructive D2O-Raman approach for targeted sorting of microbial cells with defined functional properties for single-cell genomics.

  15. Natural variation of rice blast resistance gene Pi-d2

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Studying natural variation of rice resistance (R) genes in cultivated and wild rice relatives can predict resistance stability to rice blast fungus. In the present study, the protein coding regions of rice R gene Pi-d2 in 35 rice accessions of subgroups, aus (AUS), indica (IND), temperate japonica (...

  16. Contribution of dopamine D1 and D2 receptors to amygdala activity in human.

    PubMed

    Takahashi, Hidehiko; Takano, Harumasa; Kodaka, Fumitoshi; Arakawa, Ryosuke; Yamada, Makiko; Otsuka, Tatsui; Hirano, Yoshiyuki; Kikyo, Hideyuki; Okubo, Yoshiro; Kato, Motoichiro; Obata, Takayuki; Ito, Hiroshi; Suhara, Tetsuya

    2010-02-24

    Several animal studies have demonstrated functional roles of dopamine (DA) D1 and D2 receptors in amygdala activity. However, the contribution of DA D1 and D2 receptors to amygdala response induced by affective stimuli in human is unknown. To investigate the contribution of DA receptor subtypes to amygdala reactivity in human, we conducted a multimodal in vivo neuroimaging study in which DA D1 and D2 receptor bindings in the amygdala were measured with positron emission tomography (PET), and amygdala response induced by fearful faces was assessed by functional magnetic resonance imaging (fMRI) in healthy volunteers. We used multimodality voxelwise correlation analysis between fMRI signal and DA receptor binding measured by PET. DA D1 binding in the amygdala was positively correlated with amygdala signal change in response to fearful faces, but DA D2 binding in the amygdala was not related to amygdala signal change. DA D1 receptors might play a major role in enhancing amygdala response when sensory inputs are affective.

  17. VUV Fourier-transform absorption study of the Lyman and Werner bands in D2.

    PubMed

    de Lange, Arno; Dickenson, Gareth D; Salumbides, Edcel J; Ubachs, Wim; de Oliveira, Nelson; Joyeux, Denis; Nahon, Laurent

    2012-06-21

    An extensive survey of the D(2) absorption spectrum has been performed with the high-resolution VUV Fourier-transform spectrometer employing synchrotron radiation. The frequency range of 90,000-119,000 cm(-1) covers the full depth of the potential wells of the B (1)Σ(u)(+), B' (1)Σ(u)(+), and C (1)Π(u) electronic states up to the D(1s) + D(2l) dissociation limit. Improved level energies of rovibrational levels have been determined up to respectively v = 51, v = 13, and v = 20. Highest resolution is achieved by probing absorption in a molecular gas jet with slit geometry, as well as in a liquid helium cooled static gas cell, resulting in line widths of ≈0.35 cm(-1). Extended calibration methods are employed to extract line positions of D(2) lines at absolute accuracies of 0.03 cm(-1). The D (1)Π(u) and B'' (1)Σ(u)(+) electronic states correlate with the D(1s) + D(3l]) dissociation limit, but support a few vibrational levels below the second dissociation limit, respectively, v = 0-3 and v = 0-1, and are also included in the presented study. The complete set of resulting level energies is the most comprehensive and accurate data set for D(2). The observations are compared with previous studies, both experimental and theoretical.

  18. R3D-2-MSA: the RNA 3D structure-to-multiple sequence alignment server

    PubMed Central

    Cannone, Jamie J.; Sweeney, Blake A.; Petrov, Anton I.; Gutell, Robin R.; Zirbel, Craig L.; Leontis, Neocles

    2015-01-01

    The RNA 3D Structure-to-Multiple Sequence Alignment Server (R3D-2-MSA) is a new web service that seamlessly links RNA three-dimensional (3D) structures to high-quality RNA multiple sequence alignments (MSAs) from diverse biological sources. In this first release, R3D-2-MSA provides manual and programmatic access to curated, representative ribosomal RNA sequence alignments from bacterial, archaeal, eukaryal and organellar ribosomes, using nucleotide numbers from representative atomic-resolution 3D structures. A web-based front end is available for manual entry and an Application Program Interface for programmatic access. Users can specify up to five ranges of nucleotides and 50 nucleotide positions per range. The R3D-2-MSA server maps these ranges to the appropriate columns of the corresponding MSA and returns the contents of the columns, either for display in a web browser or in JSON format for subsequent programmatic use. The browser output page provides a 3D interactive display of the query, a full list of sequence variants with taxonomic information and a statistical summary of distinct sequence variants found. The output can be filtered and sorted in the browser. Previous user queries can be viewed at any time by resubmitting the output URL, which encodes the search and re-generates the results. The service is freely available with no login requirement at http://rna.bgsu.edu/r3d-2-msa. PMID:26048960

  19. Official portrait of STS-55 SL-D2 Payload Specialist 2 Hans Schlegel

    NASA Technical Reports Server (NTRS)

    1993-01-01

    German Payload Specialist 2 Hans Schlegel poses for his Official portrait. Schlegel is assigned to the STS-55 Columbia, Orbiter Vehicle (OV) 102, Spacelab Deutsche 2 (SL-D2) mission. This is the second dedicated German Spacelab flight. United States and German flags and a space shuttle orbiter model in launch configuration create the backdrop.

  20. Systemic Blockade of D2-Like Dopamine Receptors Facilitates Extinction of Conditioned Fear in Mice

    ERIC Educational Resources Information Center

    Ponnusamy, Ravikumar; Nissim, Helen A.; Barad, Mark

    2005-01-01

    Extinction of conditioned fear in animals is the explicit model of behavior therapy for human anxiety disorders, including panic disorder, obsessive-compulsive disorder, and post-traumatic stress disorder. Based on previous data indicating that fear extinction in rats is blocked by quinpirole, an agonist of dopamine D2 receptors, we hypothesized…

  1. 26 CFR 1.411(d)-2 - Termination or partial termination; discontinuance of contributions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Bonus Plans, Etc. § 1.411(d)-2 Termination or partial termination; discontinuance of contributions. (a... such plan is not a qualified trust) unless the plan provides that— (i) Upon the termination or partial... partial termination of the plan (or, in the case of a plan to which section 412 does not apply, upon...

  2. Repeated cocaine administration results in supersensitivity of striatal D-2 dopamine autoreceptors to pergolide

    SciTech Connect

    Dwoskin, L.P.; Peris, J.; Yasuda, R.P.; Philpott, K.; Zahniser, N.R.

    1988-01-01

    Groups of rats administered cocaine-HCl (10 mg/kg, i.p.) or saline either acutely or once daily for 8 or 14 days were killed 24 hrs after the last dose. In striatal slices prelabelled with (/sup 3/H)DA, modulation of (/sup 3/H)-overflow by pergolide was used to measure D-2 autoreceptor activity. Compared to the contemporaneous control group pergolide produced a greater inhibition only in striatal slices from rats treated repeatedly with cocaine. In radioligand binding studies using striatal membranes from control rats, pergolide had a 500-fold greater affinity for the D-2, as opposed to the D-1, dopamine (DA) receptor subtype. These results indicate that repeated treatment with cocaine produces supersensitive striatal D-2 release-modulating autoreceptors consistent with a compensatory change to diminish the effect of elevated synaptic concentrations of DA produced by cocaine. In contrast, supersensitivity of D-2 receptors was not detected in (/sup 3/H)spiperone binding assays. 31 references, 2 figures, 1 table.

  3. 3D-2D registration of cerebral angiograms: a method and evaluation on clinical images.

    PubMed

    Mitrovic, Uroš; Špiclin, Žiga; Likar, Boštjan; Pernuš, Franjo

    2013-08-01

    Endovascular image-guided interventions (EIGI) involve navigation of a catheter through the vasculature followed by application of treatment at the site of anomaly using live 2D projection images for guidance. 3D images acquired prior to EIGI are used to quantify the vascular anomaly and plan the intervention. If fused with the information of live 2D images they can also facilitate navigation and treatment. For this purpose 3D-2D image registration is required. Although several 3D-2D registration methods for EIGI achieve registration accuracy below 1 mm, their clinical application is still limited by insufficient robustness or reliability. In this paper, we propose a 3D-2D registration method based on matching a 3D vasculature model to intensity gradients of live 2D images. To objectively validate 3D-2D registration methods, we acquired a clinical image database of 10 patients undergoing cerebral EIGI and established "gold standard" registrations by aligning fiducial markers in 3D and 2D images. The proposed method had mean registration accuracy below 0.65 mm, which was comparable to tested state-of-the-art methods, and execution time below 1 s. With the highest rate of successful registrations and the highest capture range the proposed method was the most robust and thus a good candidate for application in EIGI.

  4. Oncometabolite d-2-hydroxyglutarate impairs α-ketoglutarate dehydrogenase and contractile function in rodent heart

    PubMed Central

    Karlstaedt, Anja; Zhang, Xiaotian; Vitrac, Heidi; Harmancey, Romain; Vasquez, Hernan; Wang, Jing Han; Goodell, Margaret A.; Taegtmeyer, Heinrich

    2016-01-01

    Hematologic malignancies are frequently associated with cardiac pathologies. Mutations of isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in a subset of acute myeloid leukemia patients, causing metabolic and epigenetic derangements. We have now discovered that altered metabolism in leukemic cells has a profound effect on cardiac metabolism. Combining mathematical modeling and in vivo as well as ex vivo studies, we found that increased amounts of the oncometabolite d-2-hydroxyglutarate (D2-HG), produced by IDH2 mutant leukemic cells, cause contractile dysfunction in the heart. This contractile dysfunction is associated with impaired oxidative decarboxylation of α-ketoglutarate, a redirection of Krebs cycle intermediates, and increased ATP citrate lyase (ACL) activity. Increased availability of D2-HG also leads to altered histone methylation and acetylation in the heart. We propose that D2-HG promotes cardiac dysfunction by impairing α-ketoglutarate dehydrogenase and induces histone modifications in an ACL-dependent manner. Collectively, our results highlight the impact of cancer cell metabolism on function and metabolism of the heart. PMID:27582470

  5. Experimental clarification of the desorption of H 2, D 2 and He mixtures from cryosorption pumps

    NASA Astrophysics Data System (ADS)

    Terashita, Masashi; Fukada, Satoshi

    2011-10-01

    The behavior of dynamic desorption of He, H 2 and D 2 from a cryosorption pump is experimentally investigated for simplified rough separation of D-T fuel exhaust from impurities. As a fundamental study to separate the unburned D-T fuel and impurities dynamically, the discharge rates of H 2 and D 2 (as a representative of T 2), He (as a major impurity) are determined as a function of time and temperature, when the cryosorption pump is regenerated from 10 K to the room temperature of 285-305 K. The release behavior of H 2 and D 2 is compared, and the desorption isotherms of H 2, D 2 and He for activated carbon used in the cryosorption pump are determined from their respective discharge curves. The present result may lead to provide a simplified technique to decrease the throughput of the following fuel purification system and to decrease the tritium inventory by rapid separation of the D-T fuel from impurities.

  6. Experimental test of Bell's inequality via the 1H(d,2He)n reaction

    SciTech Connect

    Saito, T.; Sakai, H.; Kuboki, H.; Sasano, M.; Yako, K.; Ikeda, T.; Itoh, K.; Kawabata, T.; Maeda, Y.; Suda, K.; Uesaka, T.; Matsui, N.; Satou, Y.; Sekiguchi, K.; Tamii, A.

    2005-05-06

    To test Bell's inequality, measurements of spin correlations between two protons in the spin singlet state have been performed. Proton pairs in the singlet state were produced by the 1H(d,2He)n reaction at Ed = 270 MeV.

  7. Cannabinoids Regulate Bcl-2 and Cyclin D2 Expression in Pancreatic β Cells

    PubMed Central

    Kim, Jung Seok; Rho, Jun Gi; Shin, Jung Jae; Song, Woo Keun; Lee, Eun Kyung; Egan, Josephine M.; Kim, Wook

    2016-01-01

    Recent reports have shown that cannabinoid 1 receptors (CB1Rs) are expressed in pancreatic β cells, where they induce cell death and cell cycle arrest by directly inhibiting insulin receptor activation. Here, we report that CB1Rs regulate the expression of the anti-apoptotic protein Bcl-2 and cell cycle regulator cyclin D2 in pancreatic β cells. Treatment of MIN6 and βTC6 cells with a synthetic CB1R agonist, WIN55,212–2, led to a decrease in the expression of Bcl-2 and cyclin D2, in turn inducing cell cycle arrest in G0/G1 phase and caspase-3-dependent apoptosis. Additionally, genetic deletion and pharmacological blockade of CB1Rs after injury in mice led to increased levels of Bcl-2 and cyclin D2 in pancreatic β cells. These findings provide evidence for the involvement of Bcl-2 and cyclin D2 mediated by CB1Rs in the regulation of β-cell survival and growth, and will serve as a basis for developing new therapeutic interventions to enhance β-cell function and growth in diabetes. PMID:26967640

  8. Amphetamine decreases behavioral inhibition by stimulation of dopamine D2, but not D3, receptors.

    PubMed

    van Gaalen, Marcel M; Unger, Liliane; Jongen-Rêlo, Ana-Lucia; Schoemaker, Hans; Gross, Gerhard

    2009-09-01

    Behavioral disinhibition is a manifestation of impulsive behavior that is prominent in the psychopathology of various psychiatric disorders such as addiction, attention-deficit hyperactivity disorder, mania, and personality disorders. Impulsivity may be studied by measuring anticipatory responses made before the presentation of a food-predictive, brief light stimulus in a two-choice serial reaction time task. In such serial reaction time tasks, amphetamine has been shown to produce dose-dependent increases in premature responding in a manner dependent on dopamine D(2)-like receptor stimulation. So far, it is unknown whether it is the D(2) or D(3) receptor that is involved in this form of impulsivity. In this study, rats were trained in a two-choice serial reaction time task until baseline performance was stable. Next, effects of the dopamine D(2) preferring antagonist L-741,626 and selective D(3) antagonist SB-277011 were assessed alone and in the presence of amphetamine. Neither L-741,626 nor SB-277011 affected behavioral inhibition, although the latter significantly increased reaction time at 10 mg/kg. Amphetamine dose-dependently increased impulsivity. The effect of amphetamine was attenuated by L-741,626 (3 mg/kg), whereas SB-277011 (3 mg/kg) had no effect. Therefore, amphetamine-induced behavioral disinhibition depends on D(2), but not D(3), receptor stimulation.

  9. 11 CFR 102.4 - Administrative termination (2 U.S.C. 433(d)(2)).

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 11 Federal Elections 1 2010-01-01 2010-01-01 false Administrative termination (2 U.S.C. 433(d)(2)). 102.4 Section 102.4 Federal Elections FEDERAL ELECTION COMMISSION GENERAL REGISTRATION, ORGANIZATION... committee's last report disclosed minimal expenditures; (4) The committee's primary purpose for filing...

  10. R3D-2-MSA: the RNA 3D structure-to-multiple sequence alignment server.

    PubMed

    Cannone, Jamie J; Sweeney, Blake A; Petrov, Anton I; Gutell, Robin R; Zirbel, Craig L; Leontis, Neocles

    2015-07-01

    The RNA 3D Structure-to-Multiple Sequence Alignment Server (R3D-2-MSA) is a new web service that seamlessly links RNA three-dimensional (3D) structures to high-quality RNA multiple sequence alignments (MSAs) from diverse biological sources. In this first release, R3D-2-MSA provides manual and programmatic access to curated, representative ribosomal RNA sequence alignments from bacterial, archaeal, eukaryal and organellar ribosomes, using nucleotide numbers from representative atomic-resolution 3D structures. A web-based front end is available for manual entry and an Application Program Interface for programmatic access. Users can specify up to five ranges of nucleotides and 50 nucleotide positions per range. The R3D-2-MSA server maps these ranges to the appropriate columns of the corresponding MSA and returns the contents of the columns, either for display in a web browser or in JSON format for subsequent programmatic use. The browser output page provides a 3D interactive display of the query, a full list of sequence variants with taxonomic information and a statistical summary of distinct sequence variants found. The output can be filtered and sorted in the browser. Previous user queries can be viewed at any time by resubmitting the output URL, which encodes the search and re-generates the results. The service is freely available with no login requirement at http://rna.bgsu.edu/r3d-2-msa.

  11. Complete Genome Sequence of Acinetobacter sp. Strain NCu2D-2 Isolated from a Mouse

    PubMed Central

    Blaschke, Ulrike

    2017-01-01

    ABSTRACT Whole-genome sequencing of Acinetobacter sp. strain NCu2D-2, isolated from the trachea of a mouse, revealed the presence of a plasmid of 309,964 bp with little overall similarity to known plasmids and enriched in insertion sequences (ISs) closely related to IS elements known from the nosocomial pathogen Acinetobacter baumannii. PMID:28126932

  12. Part 1 of 3 of panorama with HABS CA2783D2 and ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    Part 1 of 3 of panorama with HABS CA-2783-D-2 and HABS CA-2783-D-3. View of north elevation of Building No. 9. Hinkley Avenue in foreground, looking south - Easter Hill Village, Building No. 11, South side of Hinkley Avenue, west of South Twenty-Sixth Street, Richmond, Contra Costa County, CA

  13. Novel regulation of p38gamma by dopamine D2 receptors during hypoxia.

    PubMed

    Conrad, P W; Millhorn, D E; Beitner-Johnson, D

    2000-07-01

    The p38 signalling pathway is part of the MAPK superfamily and is activated by various stressors. Our previous results have shown that two p38 isoforms, p38alpha and p38gamma, are activated by hypoxia in the neural-like PC12 cell line. PC12 cells also synthesize and secrete catecholamines, including dopamine, in response to hypoxia. We have now used this system to study the interaction between D2-dopamine receptor signalling and the p38 stress-activated protein kinases. Our results show that two D2 receptor antagonists, butaclamol and sulpiride, enhance hypoxia-induced phosphorylation of p38gamma, but not p38. This effect persists in protein kinase A (PKA)-deficient PC12 cells, demonstrating that p38gamma modulation by the D2 receptor is independent of the cAMP/PKA signalling system. We further show that removal of extracellular calcium blocks the hypoxia-induced increase in p38gamma activity. These results are the first to demonstrate that p38gamma can be regulated by the D2 receptor and calcium following hypoxic exposure.

  14. Dopamine binds calmodulin during autoregulation of dopaminergic D2 receptor signaling through CaMKIIα-calmodulin complex.

    PubMed

    Laoye, B J; Okurumeh, O A; Obagaye, O V; Olagunju, M O; Bankole, O O; Olubiyi, O O; Ogundele, O M

    2016-01-01

    The role of dopaminergic D2 receptor (D2R) autoregulation in dopamine (DA) neurotransmission cannot be overemphasized in cause and progression of disorders associated with complex behaviors. Although previous studies have shown that D2R is structurally and physiologically linked with calcium/calmodulin-dependent kinase II (CaMKIIα), however, the role of calmodulin in the CaMKIIα complex in D2R regulation remains elusive. In this study, using structural biology modeling softwares (iGEMDOCK and CueMol), we have shown the interaction between D2R, CaMKIIα, calmodulin, and DA under varying conditions. The outcomes of this study suggest that CaMKIIα causes a change in DA binding affinity to the D2R receptive site while the detached DA binds to calmodulin to stop the activity of D2R in the D2R-dopaminergic D1 receptor (D1R) heteromer. Ultimately, we concluded that D2R autoregulates to stop its heteromeric combination with D1R. D2R interacts with D1R to facilitate calcium movement that activates calmodulin, then CaMKIIα. The CaMKIIα-calmodulin complex changes the affinity of DA-D2R causing DA to break free and bind with calmodulin.

  15. Measurements of d2n and A1n : Probing the neutron spin structure

    NASA Astrophysics Data System (ADS)

    Flay, D.; Posik, M.; Parno, D. S.; Allada, K.; Armstrong, W. R.; Averett, T.; Benmokhtar, F.; Bertozzi, W.; Camsonne, A.; Canan, M.; Cates, G. D.; Chen, C.; Chen, J.-P.; Choi, S.; Chudakov, E.; Cusanno, F.; Dalton, M. M.; Deconinck, W.; de Jager, C. W.; Deng, X.; Deur, A.; Dutta, C.; Fassi, L. El; Franklin, G. B.; Friend, M.; Gao, H.; Garibaldi, F.; Gilad, S.; Gilman, R.; Glamazdin, O.; Golge, S.; Gomez, J.; Guo, L.; Hansen, O.; Higinbotham, D. W.; Holmstrom, T.; Huang, J.; Hyde, C.; Ibrahim, H. F.; Jiang, X.; Jin, G.; Katich, J.; Kelleher, A.; Kolarkar, A.; Korsch, W.; Kumbartzki, G.; LeRose, J. J.; Lindgren, R.; Liyanage, N.; Long, E.; Lukhanin, A.; Mamyan, V.; McNulty, D.; Meziani, Z.-E.; Michaels, R.; Mihovilovič, M.; Moffit, B.; Muangma, N.; Nanda, S.; Narayan, A.; Nelyubin, V.; Norum, B.; Nuruzzaman, Oh, Y.; Peng, J. C.; Qian, X.; Qiang, Y.; Rakhman, A.; Ransome, R. D.; Riordan, S.; Saha, A.; Sawatzky, B.; Shabestari, M. H.; Shahinyan, A.; Širca, S.; Solvignon, P.; Subedi, R.; Sulkosky, V.; Tobias, W. A.; Troth, W.; Wang, D.; Wang, Y.; Wojtsekhowski, B.; Yan, X.; Yao, H.; Ye, Y.; Ye, Z.; Yuan, L.; Zhan, X.; Zhang, Y.; Zhang, Y.-W.; Zhao, B.; Zheng, X.; Jefferson Lab Hall A Collaboration

    2016-09-01

    We report on the results of the E06-014 experiment performed at Jefferson Lab in Hall A, where a precision measurement of the twist-3 matrix element d2 of the neutron (d2n) was conducted. The quantity d2n represents the average color Lorentz force a struck quark experiences in a deep inelastic electron scattering event off a neutron due to its interaction with the hadronizing remnants. This color force was determined from a linear combination of the third moments of the 3He spin structure functions, g1 and g2, after nuclear corrections had been applied to these moments. The structure functions were obtained from a measurement of the unpolarized cross section and of double-spin asymmetries in the scattering of a longitudinally polarized electron beam from a transversely and a longitudinally polarized 3He target. The measurement kinematics included two average Q2 bins of 3.2 GeV2 and 4.3 GeV2 , and Bjorken-x 0.25 ≤x ≤0.90 covering the deep inelastic and resonance regions. We have found that d2n is small and negative for ⟨Q2⟩ =3.2 GeV2 , and even smaller for ⟨Q2⟩ =4.3 GeV2 , consistent with the results of a lattice QCD calculation. The twist-4 matrix element f2n was extracted by combining our measured d2n with the world data on the first moment in x of g1n, Γ1n. We found f2n to be roughly an order of magnitude larger than d2n. Utilizing the extracted d2n and f2n data, we separated the Lorentz color force into its electric and magnetic components, FEy ,n and FBy ,n, and found them to be equal and opposite in magnitude, in agreement with the predictions from an instanton model but not with those from QCD sum rules. Furthermore, using the measured double-spin asymmetries, we have extracted the virtual photon-nucleon asymmetry on the neutron A1n, the structure function ratio g1n/F1n, and the quark ratios (Δ u +Δ u ¯)/(u +u ¯) and (Δ d +Δ d ¯)/(d +d ¯). These results were found to be consistent with deep-inelastic scattering world data and with the

  16. Disruption of cerebellar microzonal organization in GluD2 (GluRδ2) knockout mouse

    PubMed Central

    Hashizume, Miki; Miyazaki, Taisuke; Sakimura, Kenji; Watanabe, Masahiko; Kitamura, Kazuo; Kano, Masanobu

    2013-01-01

    Cerebellar cortex has an elaborate rostrocaudal organization comprised of numerous microzones. Purkinje cells (PCs) in the same microzone show synchronous activity of complex spikes (CSs) evoked by excitatory inputs from climbing fibers (CFs) that arise from neurons in the inferior olive (IO). The synchronous CS activity is considered to depend on electrical coupling among IO neurons and anatomical organization of the olivo-cerebellar projection. To determine how the CF–PC wiring contributes to the formation of microzone, we examined the synchronous CS activities between neighboring PCs in the glutamate receptor δ2 knockout (GluD2 KO) mouse in which exuberant surplus CFs make ectopic innervations onto distal dendrites of PCs. We performed in vivo two-photon calcium imaging for PC populations to detect CF inputs. Neighboring PCs in GluD2 KO mice showed higher synchrony of calcium transients than those in wild-type (control) mice. Moreover, the synchrony in GluD2 KO mice hardly declined with mediolateral separation between PCs up to ~200 μm, which was in marked contrast to the falloff of the synchrony in control mice. The enhanced synchrony was only partially affected by the blockade of gap junctional coupling. On the other hand, transverse CF collaterals in GluD2 KO mice extended beyond the border of microzone and formed locally clustered ectopic synapses onto dendrites of neighboring PCs. Furthermore, PCs in GluD2 KO mice exhibited clustered firing (Cf), the characteristic CF response that was not found in PCs of wild-type mice. Importantly, Cf was often associated with localized calcium transients in distal dendrites of PCs, which are likely to contribute to the enhanced synchrony of calcium signals in GluD2 KO mice. Thus, our results indicate that CF signals in GluD2 KO mice propagate across multiple microzones, and that proper formation of longitudinal olivo-cerebellar projection is essential for the spatiotemporal organization of CS activity in the

  17. Comparison of metabolism of vitamins D2 and D3 in children with nutritional rickets.

    PubMed

    Thacher, Tom D; Fischer, Philip R; Obadofin, Michael O; Levine, Michael A; Singh, Ravinder J; Pettifor, John M

    2010-09-01

    Children with calcium-deficiency rickets may have increased vitamin D requirements and respond differently to vitamin D(2) and vitamin D(3). Our objective was to compare the metabolism of vitamins D(2) and D(3) in rachitic and control children. We administered an oral single dose of vitamin D(2) or D(3) of 1.25 mg to 49 Nigerian children--28 with active rickets and 21 healthy controls. The primary outcome measure was the incremental change in vitamin D metabolites. Baseline serum 25-hydroxyvitamin D [25(OH)D] concentrations ranged from 7 to 24 and 15 to 34 ng/mL in rachitic and control children, respectively (p < .001), whereas baseline 1,25-dihydroxyvitamin D [1,25(OH)(2)D] values (mean ± SD) were 224 ± 72 and 121 ± 34 pg/mL, respectively (p < .001), and baseline 24,25-dihydroxyvitamin D [24,25(OH)(2)D] values were 1.13 ± 0.59 and 4.03 ± 1.33 ng/mL, respectively (p < .001). The peak increment in 25(OH)D was on day 3 and was similar with vitamins D(2) and D(3) in children with rickets (29 ± 17 and 25 ± 11 ng/mL, respectively) and in control children (33 ± 13 and 31 ± 16 ng/mL, respectively). 1,25(OH)(2)D rose significantly (p < .001) and similarly (p = .18) on day 3 by 166 ± 80 and 209 ± 83 pg/mL after vitamin D(2) and D(3) administration, respectively, in children with rickets. By contrast, control children had no significant increase in 1,25(OH)(2)D (19 ± 28 and 16 ± 38 pg/mL after vitamin D(2) and D(3) administration, respectively). We conclude that in the short term, vitamins D(2) and D(3) similarly increase serum 25(OH)D concentrations in rachitic and healthy children. A marked increase in 1,25(OH)(2)D in response to vitamin D distinguishes children with putative dietary calcium-deficiency rickets from healthy children, consistent with increased vitamin D requirements in children with calcium-deficiency rickets. © 2010 American Society for Bone and Mineral

  18. Metabolic fate of radiolabeled prostaglandin D2 in a normal human male volunteer

    SciTech Connect

    Liston, T.E.; Roberts, L.J. 2d.

    1985-10-25

    50 microCi of (TH)prostaglandin D2 tracer (100 Ci/mmol) was infused intravenously into a normal human male volunteer. 75% of the infused radioactivity was excreted into the urine within 5 h. This urine was added to urine obtained from two mastocytosis patients with marked overproduction of prostaglandin D2. Radiolabeled prostaglandin D2 urinary metabolites were chromatographically isolated and purified and subsequently identified by gas chromatography-mass spectrometry. 25 metabolites were identified. 23 of these compounds comprising 37% of the recovered radioactivity had prostaglandin F-ring structures, and only two metabolites comprising 2.7% of the recovered radioactivity retained the prostaglandin D-ring structure. The single most abundant metabolite identified was 9,11-dihydroxy-15-oxo-2,3,18,19-tetranorprost-5-ene-1,20-dioic acid which was isolated in a tricyclic form as a result of formation of a lower side chain hemiketal followed by lactonization of the terminal carboxyl and the hemiketal hydroxyl. Different isomeric forms of several prostaglandin F-ring metabolites were identified. An isomer of prostaglandin F2 alpha was also excreted intact into the urine as a metabolite of prostaglandin D2. 15 PGF-ring compounds were treated with n-butylboronic acid and 13 failed to form a boronate derivative, suggesting that the orientation of the hydroxyl group at C-11 in these 13 metabolites is beta. This study documents that prostaglandin D2 is metabolized to prostaglandin F-ring metabolites in vivo in humans. These results also bring into question the accuracy of quantifying prostaglandin F2 alpha metabolites as a specific index of endogenous prostaglandin F2 alpha biosynthesis, as well as quantifying urinary prostaglandin F2 alpha as an accurate index of renal production of prostaglandin F2 alpha.

  19. Kinetics of DNA unwinding by the RecD2 helicase from Deinococcus radiodurans.

    PubMed

    Shadrick, William R; Julin, Douglas A

    2010-06-04

    RecD2 from Deinococcus radiodurans is a superfamily 1 DNA helicase that is homologous to the Escherichia coli RecD protein but functions outside the context of RecBCD enzyme. We report here on the kinetics of DNA unwinding by RecD2 under single and multiple turnover conditions. There is little unwinding of 20-bp substrates by preformed RecD2-dsDNA complexes when excess ssDNA is present to trap enzyme molecules not bound to the substrate. A shorter 12-bp substrate is unwound rapidly under single turnover conditions. The 12-bp unwinding reaction could be simulated with a mechanism in which the DNA is unwound in two kinetic steps with rate constant of k(unw) = 5.5 s(-1) and a dissociation step from partially unwound DNA of k(off) = 1.9 s(-1). These results indicate a kinetic step size of about 3-4 bp, unwinding rate of about 15-20 bp/s, and low processivity (p = 0.74). The reaction time courses with 20-bp substrates, determined under multiple turnover conditions, could be simulated with a four-step mechanism and rate constant values very similar to those for the 12-bp substrate. The results indicate that the faster unwinding of a DNA substrate with a forked end versus only a 5'-terminal single-stranded extension can be accounted for by a difference in the rate of enzyme binding to the DNA substrates. Analysis of reactions done with different RecD2 concentrations indicates that the enzyme forms an inactive dimer or other oligomer at high enzyme concentrations. RecD2 oligomers can be detected by glutaraldehyde cross-linking but not by size exclusion chromatography.

  20. Biphasic role of dopamine on female sexual behaviour via D2 receptors in the mediobasal hypothalamus.

    PubMed

    Fabre-Nys, Claude; Chesneau, Didier; de la Riva, Carlos; Hinton, Michael R; Locatelli, Alain; Ohkura, Satoshi; Kendrick, Keith M

    2003-03-01

    Dopamine has been implicated in the control of sexual behaviour, but its role seems quite complex and controversial. The aim of the present experiments was to investigate the effects of dopamine (DA) acting on D2 receptors in the mediobasal hypothalamus (MBH) on sexual behaviour in female sheep. To achieve this, the D2 agonist, quinpirole, was administered bilaterally via microdialysis probes into the MBH of ovariectomized ewes either before or after oestradiol (E2) administration. Quinpirole (100 ng/ml) infused for 6 h just before E2 hastened the onset of oestrus behaviour and the luteinizing hormone surge, whereas the same treatment given 6-12 h or 18-21 h after E2 decreased the intensity of sexual receptivity without affecting LH or prolactin secretion. We then tested the hypothesis that E2 stimulates the onset of oestrus partly by decreasing DA activation of D2 receptors. In this case the D2 antagonists pimozide or spiperone (100 ng/ml) were infused into the MBH via microdialysis probes for 11 h in the absence of E2 administration. A significant number of ewes showed induction of receptivity with both antagonists, although its intensity was significantly lower than that induced by E2. These treatments generally did not significantly alter extracellular concentrations of monoamines or aminoacids although quinpirole modulated the ability of sexual interactions to increase noradrenaline release. These experiments show that DA acts via D2 receptors in the MBH to control female sexual behaviour in a biphasic manner: the onset of sexual motivation and receptivity requiring an initial increase in activation followed by a decrease. This dual action could explain some of the controversies concerning DA action on sexual behaviour.

  1. Involvement of dopamine D2 receptors in addictive-like behaviour for acetaldehyde.

    PubMed

    Brancato, Anna; Plescia, Fulvio; Marino, Rosa Anna Maria; Maniaci, Giuseppe; Navarra, Michele; Cannizzaro, Carla

    2014-01-01

    Acetaldehyde, the first metabolite of ethanol, is active in the central nervous system, where it exerts motivational properties. Acetaldehyde is able to induce drinking behaviour in operant-conflict paradigms that resemble the core features of the addictive phenotype: drug-intake acquisition and maintenance, drug-seeking, relapse and drug use despite negative consequences. Since acetaldehyde directly stimulates dopamine neuronal firing in the mesolimbic system, the aim of this study was the investigation of dopamine D2-receptors' role in the onset of the operant drinking behaviour for acetaldehyde in different functional stages, by the administration of two different D2-receptor agonists, quinpirole and ropinirole. Our results show that acetaldehyde was able to induce and maintain a drug-taking behaviour, displaying an escalation during training, and a reinstatement behaviour after 1-week forced abstinence. Acetaldehyde operant drinking behaviour involved D2-receptor signalling: in particular, quinpirole administration at 0.03 mg/kg, induced a significant decrease in the number of lever presses both in extinction and in relapse. Ropinirole, administered at 0.03 mg/kg during extinction, did not produce any modification but, when administered during abstinence, induced a strong decrease in acetaldehyde intake in the following relapse session. Taken together, our data suggest that acetaldehyde exerts its own motivational properties, involving the dopaminergic transmission: indeed, activation of pre-synaptic D2-receptors by quinpirole, during extinction and relapse, negatively affects operant behaviour for acetaldehyde, likely decreasing acetaldehyde-induced dopamine release. The activation of post-synaptic D2-receptors by ropinirole, during abstinence, decreases the motivation to the consecutive reinstatement of acetaldehyde drinking behaviour, likely counteracting the reduction in the dopaminergic tone typical of withdrawal. These data further strengthen the evidence

  2. Interaction between vitamin D 2 and magnesium in liposomes: Differential scanning calorimetry and FTIR spectroscopy studies

    NASA Astrophysics Data System (ADS)

    Toyran, Neslihan; Severcan, Feride

    2007-08-01

    Magnesium (Mg 2+) ion is of great importance in physiology by its intervention in 300 enzymatic systems, its role in membrane structure, its function in neuromuscular excitability and vitamin D metabolism and/or action. In the present study, the interaction of Mg 2+, at low (1 mole %) and high (7 mole %) concentrations with dipalmitoyl phosphatidylcholine (DPPC) liposomes has been studied in the presence and absence of vitamin D 2 (1 mole %) by using two noninvasive techniques, namely differential scanning calorimetry (DSC) and Fourier transform infrared (FTIR) spectroscopy. DSC studies reveal that the presence of vitamin D 2 in the pure or Mg 2+ (at both low and high concentrations) containing liposomes diminishes the pretransition. The calorimetric results also reveal that, inclusion of Mg 2+ (more significantly at high concentration) into pure or vitamin D 2 containing DPPC liposomes increases the main phase transition temperature. The investigation of the CH 2 symmetric, the CH 3 asymmetric, the C dbnd O stretching, and the PO2- antisymmetric double bond stretching bands in FTIR spectra with respect to changes occurring in the wavenumber and/or the bandwidth values as a function of temperature reveal that, inclusion of vitamin D 2 or Mg 2+ into pure DPPC liposomes orders and decreases the dynamics of the acyl chains in both gel and liquid-crystalline phases and does not induce hydrogen bond formation in the interfacial region. Furthermore, the dynamics of the head groups of the liposomes decreases in both phases. Our findings reveal that, simultaneous presence of vitamin D 2 and Mg 2+ alters the effect of each other, which is reflected as a decrease in the interactions between these two additives within the model membrane.

  3. Pituitary and Brain Dopamine D2 Receptors Regulate Liver Gene Sexual Dimorphism

    PubMed Central

    Ramirez, Maria Cecilia; Ornstein, Ana Maria; Luque, Guillermina Maria; Perez Millan, Maria Ines; Garcia-Tornadu, Isabel; Rubinstein, Marcelo

    2015-01-01

    Liver sexual gene dimorphism, which depends mainly on specific patterns of GH secretion, may underlie differential susceptibility to some liver diseases. Because GH and prolactin secretion are regulated by dopaminergic pathways, we studied the participation of brain and lactotrope dopamine 2 receptors (D2Rs) on liver gene sexual dimorphism, to explore a link between the brain and liver gene expression. We used global D2R knockout mice (Drd2−/−) and conducted a functional dissection strategy based on cell-specific Drd2 inactivation in neurons (neuroDrd2KO) or pituitary lactotropes. Disruption of neuronal D2Rs (which impaired the GH axis) decreased most of male or female-predominant class I liver genes and increased female–predominant class II genes in males, consistent with the positive (class I) or negative (class II) regulation of these genes by GH. Notably, sexual dimorphism was lost for class I and II genes in neuroDrd2KO mice. Disruption of lactotrope D2Rs did not modify class I or II genes in either sex, because GH axis was preserved. But surprisingly, 1 class II gene (Prlr) and female-predominant class I genes were markedly up-regulated in lacDrd2KO females, pointing to direct or indirect effects of prolactin in the regulation of selected female-predominant liver genes. This suggestion was strengthened in the hyperprolactinemic Drd2−/− female mouse, in which increased expression of the same 4 liver genes was observed, despite a decreased GH axis. We hereby demonstrate endocrine-mediated D2R actions on sexual dimorphic liver gene expression, which may be relevant during chronic dopaminergic medications in psychiatric disease. PMID:25545383

  4. Low expression of D2R and Wntless correlates with high motivation for heroin.

    PubMed

    Tacelosky, Diana M; Alexander, Danielle N; Morse, Megan; Hajnal, Andras; Berg, Arthur; Levenson, Robert; Grigson, Patricia S

    2015-12-01

    Drug overdose now exceeds car accidents as the leading cause of accidental death in the United States. Of those drug overdoses, a large percentage of the deaths are due to heroin and/or pharmaceutical overdose, specifically misuse of prescription opioid analgesics. It is imperative, then, that we understand the mechanisms that lead to opioid abuse and addiction. The rewarding actions of opioids are mediated largely by the mu-opioid receptor (MOR), and signaling by this receptor is modulated by various interacting proteins. The neurotransmitter dopamine also contributes to opioid reward, and opioid addiction has been linked to reduced expression of dopamine D2 receptors (D2R) in the brain. That said, it is not known if alterations in the expression of these proteins relate to drug exposure and/or to the "addiction-like" behavior exhibited for the drug. Here, we held total drug self-administration constant across acquisition and showed that reduced expression of the D2R and the MOR interacting protein, Wntless, in the medial prefrontal cortex was associated with greater addiction-like behavior for heroin in general and with a greater willingness to work for the drug in particular. In contrast, reduced expression of the D2R in the nucleus accumbens and hippocampus was correlated with greater seeking during signaled nonavailability of the drug. Taken together, these data link reduced expression of both the D2R and Wntless to the explicit motivation for the drug rather than to differences in total drug intake per se.

  5. Low Expression of D2R and Wntless Correlates with High Motivation for Heroin

    PubMed Central

    Tacelosky, Diana M.; Alexander, Danielle N.; Morse, Megan; Hajnal, Andras; Berg, Arthur; Levenson, Robert; Grigson, Patricia S.

    2015-01-01

    Drug overdose now exceeds car accidents as the leading cause of accidental death in the U.S. Of those drug overdoses, a large percentage of the deaths are due to heroin and/or pharmaceutical overdose, specifically misuse of prescription opioid analgesics. It is imperative, then, that we understand the mechanisms that lead to opioid abuse and addiction. The rewarding actions of opioids are mediated largely by the mu opioid receptor (MOR), and signaling by this receptor is modulated by various interacting proteins. The neurotransmitter dopamine also contributes to opioid reward, and opioid addiction has been linked to reduced expression of dopamine D2 receptors (D2R) in brain. That said, it is not known if alterations in the expression of these proteins relates to drug exposure and/or to the “addiction-like” behavior exhibited for drug. Here, we held total drug self-administration constant across acquisition and showed that reduced expression of the D2R and the MOR interacting protein, Wntless, in the medial prefrontal cortex was associated with greater “addiction-like” behavior for heroin, in general, and with a greater willingness to work for drug, in particular. In contrast, reduced expression of the D2R in the nucleus accumbens and hippocampus was correlated with greater seeking during signaled non-availability of drug. Taken together, these data link reduced expression of both the D2R and Wntless to the explicit motivation for drug, rather than to differences in total drug intake, per se. PMID:26501177

  6. Evaluation of low-dose limits in 3D-2D rigid registration for surgical guidance

    NASA Astrophysics Data System (ADS)

    Uneri, A.; Wang, A. S.; Otake, Y.; Kleinszig, G.; Vogt, S.; Khanna, A. J.; Gallia, G. L.; Gokaslan, Z. L.; Siewerdsen, J. H.

    2014-09-01

    An algorithm for intensity-based 3D-2D registration of CT and C-arm fluoroscopy is evaluated for use in surgical guidance, specifically considering the low-dose limits of the fluoroscopic x-ray projections. The registration method is based on a framework using the covariance matrix adaptation evolution strategy (CMA-ES) to identify the 3D patient pose that maximizes the gradient information similarity metric. Registration performance was evaluated in an anthropomorphic head phantom emulating intracranial neurosurgery, using target registration error (TRE) to characterize accuracy and robustness in terms of 95% confidence upper bound in comparison to that of an infrared surgical tracking system. Three clinical scenarios were considered: (1) single-view image + guidance, wherein a single x-ray projection is used for visualization and 3D-2D guidance; (2) dual-view image + guidance, wherein one projection is acquired for visualization, combined with a second (lower-dose) projection acquired at a different C-arm angle for 3D-2D guidance; and (3) dual-view guidance, wherein both projections are acquired at low dose for the purpose of 3D-2D guidance alone (not visualization). In each case, registration accuracy was evaluated as a function of the entrance surface dose associated with the projection view(s). Results indicate that images acquired at a dose as low as 4 μGy (approximately one-tenth the dose of a typical fluoroscopic frame) were sufficient to provide TRE comparable or superior to that of conventional surgical tracking, allowing 3D-2D guidance at a level of dose that is at most 10% greater than conventional fluoroscopy (scenario #2) and potentially reducing the dose to approximately 20% of the level in a conventional fluoroscopically guided procedure (scenario #3).

  7. Evaluation of low-dose limits in 3D-2D rigid registration for surgical guidance.

    PubMed

    Uneri, A; Wang, A S; Otake, Y; Kleinszig, G; Vogt, S; Khanna, A J; Gallia, G L; Gokaslan, Z L; Siewerdsen, J H

    2014-09-21

    An algorithm for intensity-based 3D-2D registration of CT and C-arm fluoroscopy is evaluated for use in surgical guidance, specifically considering the low-dose limits of the fluoroscopic x-ray projections. The registration method is based on a framework using the covariance matrix adaptation evolution strategy (CMA-ES) to identify the 3D patient pose that maximizes the gradient information similarity metric. Registration performance was evaluated in an anthropomorphic head phantom emulating intracranial neurosurgery, using target registration error (TRE) to characterize accuracy and robustness in terms of 95% confidence upper bound in comparison to that of an infrared surgical tracking system. Three clinical scenarios were considered: (1) single-view image+guidance, wherein a single x-ray projection is used for visualization and 3D-2D guidance; (2) dual-view image+guidance, wherein one projection is acquired for visualization, combined with a second (lower-dose) projection acquired at a different C-arm angle for 3D-2D guidance; and (3) dual-view guidance, wherein both projections are acquired at low dose for the purpose of 3D-2D guidance alone (not visualization). In each case, registration accuracy was evaluated as a function of the entrance surface dose associated with the projection view(s). Results indicate that images acquired at a dose as low as 4 μGy (approximately one-tenth the dose of a typical fluoroscopic frame) were sufficient to provide TRE comparable or superior to that of conventional surgical tracking, allowing 3D-2D guidance at a level of dose that is at most 10% greater than conventional fluoroscopy (scenario #2) and potentially reducing the dose to approximately 20% of the level in a conventional fluoroscopically guided procedure (scenario #3).

  8. The D1-D2 region of the large subunit ribosomal DNA as barcode for ciliates.

    PubMed

    Stoeck, T; Przybos, E; Dunthorn, M

    2014-05-01

    Ciliates are a major evolutionary lineage within the alveolates, which are distributed in nearly all habitats on our planet and are an essential component for ecosystem function, processes and stability. Accurate identification of these unicellular eukaryotes through, for example, microscopy or mating type reactions is reserved to few specialists. To satisfy the demand for a DNA barcode for ciliates, which meets the standard criteria for DNA barcodes defined by the Consortium for the Barcode of Life (CBOL), we here evaluated the D1-D2 region of the ribosomal DNA large subunit (LSU-rDNA). Primer universality for the phylum Ciliophora was tested in silico with available database sequences as well as in the laboratory with 73 ciliate species, which represented nine of 12 ciliate classes. Primers tested in this study were successful for all tested classes. To test the ability of the D1-D2 region to resolve conspecific and congeneric sequence divergence, 63 Paramecium strains were sampled from 24 mating species. The average conspecific D1-D2 variation was 0.18%, whereas congeneric sequence divergence averaged 4.83%. In pairwise genetic distance analyses, we identified a D1-D2 sequence divergence of <0.6% as an ideal threshold to discriminate Paramecium species. Using this definition, only 3.8% of all conspecific and 3.9% of all congeneric sequence comparisons had the potential of false assignments. Neighbour-joining analyses inferred monophyly for all taxa but for two Paramecium octaurelia strains. Here, we present a protocol for easy DNA amplification of single cells and voucher deposition. In conclusion, the presented data pinpoint the D1-D2 region as an excellent candidate for an official CBOL barcode for ciliated protists.

  9. Multigenerational Effects of Adolescent Morphine Exposure on Dopamine D2 Receptor Function

    PubMed Central

    Byrnes, John J.; Johnson, Nicole L.; Carini, Lindsay M.; Byrnes, Elizabeth M.

    2013-01-01

    Rationale The use and misuse of prescription opiates in adolescent populations, and in particular, adolescent female populations, has increased dramatically in the past two decades. Given the significant role that opioids play in neuroendocrine function, exposure to opiates during this critical developmental period could have significant consequences for the female, as well as her offspring. Objectives In the current set of studies, we utilized the female rat to model the transgenerational impact of adolescent opiate exposure. Methods We examined locomotor sensitization in response to the dopamine D2/D3 receptor agonist quinpirole in the adult male progeny (F1 and F2 generation) of females exposed to morphine during adolescence. All females were drug-free for at least 3 weeks prior to conception, eliminating the possibility of direct fetal exposure to morphine. Results Both F1 and F2 progeny of morphine-exposed females demonstrated attenuated locomotor sensitization following repeated quinpirole administration. These behavioral effects were coupled with increased quinpirole-induced corticosterone secretion, and up-regulated kappa opioid receptor (KOR) and dopamine D2 receptor (D2R) gene expression within the NAc. Conclusions These results suggest significant modifications in response to repeated D2R activation in the progeny of females exposed to opiates during adolescence. Given the significant role that the D2R plays in psychopathology, adolescent opiate exposure could shift the vulnerability of future offspring to psychological disorders, including addiction. Moreover, that effects are also observed in the F2 generation suggests that adolescent opiate exposure can trigger transgenerational epigenetic modifications impacting systems critical for motivated behavior. PMID:23314440

  10. Pharmacology and Structural Analysis of Ligand Binding to the Orthosteric Site of Glutamate-Like GluD2 Receptors

    PubMed Central

    Kristensen, Anders S.; Hansen, Kasper B.; Naur, Peter; Olsen, Lars; Kurtkaya, Natalie L.; Dravid, Shashank M.; Kvist, Trine; Yi, Feng; Pøhlsgaard, Jacob; Clausen, Rasmus P.; Gajhede, Michael

    2016-01-01

    The GluD2 receptor is a fundamental component of postsynaptic sites in Purkinje neurons, and is required for normal cerebellar function. GluD2 and the closely related GluD1 are classified as members of the ionotropic glutamate receptor (iGluR) superfamily on the basis of sequence similarity, but do not bind l-glutamate. The amino acid neurotransmitter D-Ser is a GluD2 receptor ligand, and endogenous D-Ser signaling through GluD2 has recently been shown to regulate endocytosis of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid–type iGluRs during synaptic plasticity in the cerebellum, such as long-term depression. Here, we investigate the pharmacology of the orthosteric binding site in GluD2 by examining the activity of analogs of D-Ser and GluN1 glycine site competitive antagonists at GluD2 receptors containing the lurcher mutation (GluD2LC), which promotes spontaneous channel activation. We identify several compounds that modulate GluD2LC, including a halogenated alanine analog as well as the kynurenic acid analog 7-chloro-4-oxo-1H-quinoline-2-carboxylic acid (7-chlorokynurenic acid; 7-CKA). By correlating thermodynamic and structural data for 7-CKA binding to the isolated GluD2 ligand binding domain (GluD2-LBD), we find that binding 7-CKA to GluD2-LBD differs from D-Ser by inducing an intermediate cleft closure of the clamshell-shaped LBD. The GluD2 ligands identified here can potentially serve as a starting point for development of GluD2-selective ligands useful as tools in studies of the signaling role of the GluD2 receptor in the brain. PMID:26661043

  11. Exploring peronality traits related to dopamine D2/3 receptor availability in striatal subregions of humans

    PubMed Central

    Caravaggio, Fernando; Fervaha, Gagan; Chung, Jun Ku; Gerretsen, Philip; Nakajima, Shinichiro; Plitman, Eric; Iwata, Yusuke; Wilson, Alan; Graff-Guerrero, Ariel

    2016-01-01

    While several studies have examined how particular personality traits are related to dopamine D2/3 receptor (D2/3R) availability in the striatum of humans, few studies have reported how multiple traits measured in the same persons are differentially related to D2/3R availability in different striatal sub-regions. We examined how personality traits measured with the Karolinska Scales of Personality are related to striatal D2/3R availability measured with [11C]-raclopride in 30 healthy humans. Based on previous literature, five personality traits were hypothesized to be most likely related to D2/3R availability: impulsiveness, monotony avoidance, detachment, social desirability, and socialization. We found self-reported impulsiveness was negatively correlated with D2/3R availability in the ventral striatum and globus pallidus. After controlling for age and gender, monotony avoidance was also negatively correlated with D2/3R availability in the ventral striatum and globus pallidus. Socialization was positively correlated with D2/3R availability in the ventral striatum and putamen. After controlling for age and gender, the relationship between socialization and D2/3R availability in these regions survived correction for multiple comparisons (p-threshold=.003). Thus, within the same persons, different personality traits are differentially related to in vivo D2/3R availability in different striatal sub-regions. PMID:26944295

  12. Plasma appearance and disappearance of an oral dose of 25-hydroxyvitamin D2 in healthy adults

    PubMed Central

    Jones, Kerry S.; Schoenmakers, Inez; Bluck, Les J. C.; Ding, Shujing; Prentice, Ann

    2012-01-01

    25-Hydroxyvitamin D (25(OH)D) half-life is a potential biomarker for investigating vitamin D metabolism and requirements. We performed a pilot study to assess the approach and practical feasibility of measuring 25(OH)D half-life after an oral dose. A total of twelve healthy Gambian men aged 18–23 years were divided into two groups to investigate the rate and timing of (1) absorption and (2) plasma disappearance after an 80 nmol oral dose of 25(OH)D2. Fasting blood samples were collected at baseline and, in the first group, every 2 h post-dose for 12 h, at 24 h, 48 h and on day 15. In the second group, fasting blood samples were collected on days 3, 4, 5, 6, 9, 12, 15, 18 and 21. Urine was collected for 2 h after the first morning void at baseline and on day 15. 25(OH)D2 plasma concentration was measured by ultra-performance liquid chromatography-tandem MS/MS and corrected for baseline. Biomarkers of vitamin D, Ca and P metabolism were measured at baseline and on day 15. The peak plasma concentration of 25(OH)D2 was 9·6 (sd 0·9) nmol/l at 4·4 (sd 1·8) h. The terminal slope of 25(OH)D2 disappearance was identified to commence from day 6. The terminal half-life of plasma 25(OH)D2 was 13·4 (sd 2·7) d. There were no significant differences in plasma 25(OH)D3, total 1,25(OH)2D, parathyroid hormone, P, Ca and ionised Ca and urinary Ca and P between baseline and day 15 and between the two groups. The present study provides data on the plasma response to oral 25(OH)D2 that will underpin and contribute to the further development of studies to investigate 25(OH)D half-life. PMID:21896243

  13. Plasma appearance and disappearance of an oral dose of 25-hydroxyvitamin D2 in healthy adults.

    PubMed

    Jones, Kerry S; Schoenmakers, Inez; Bluck, Les J C; Ding, Shujing; Prentice, Ann

    2012-04-01

    25-Hydroxyvitamin D (25(OH)D) half-life is a potential biomarker for investigating vitamin D metabolism and requirements. We performed a pilot study to assess the approach and practical feasibility of measuring 25(OH)D half-life after an oral dose. A total of twelve healthy Gambian men aged 18-23 years were divided into two groups to investigate the rate and timing of (1) absorption and (2) plasma disappearance after an 80 nmol oral dose of 25(OH)D2. Fasting blood samples were collected at baseline and, in the first group, every 2 h post-dose for 12 h, at 24 h, 48 h and on day 15. In the second group, fasting blood samples were collected on days 3, 4, 5, 6, 9, 12, 15, 18 and 21. Urine was collected for 2 h after the first morning void at baseline and on day 15. 25(OH)D2 plasma concentration was measured by ultra-performance liquid chromatography-tandem MS/MS and corrected for baseline. Biomarkers of vitamin D, Ca and P metabolism were measured at baseline and on day 15. The peak plasma concentration of 25(OH)D2 was 9·6 (sd 0·9) nmol/l at 4·4 (sd 1·8) h. The terminal slope of 25(OH)D2 disappearance was identified to commence from day 6. The terminal half-life of plasma 25(OH)D2 was 13·4 (sd 2·7) d. There were no significant differences in plasma 25(OH)D3, total 1,25(OH)2D, parathyroid hormone, P, Ca and ionised Ca and urinary Ca and P between baseline and day 15 and between the two groups. The present study provides data on the plasma response to oral 25(OH)D2 that will underpin and contribute to the further development of studies to investigate 25(OH)D half-life.

  14. Sensitivities of dopamine D1 and D2 receptor radioligands to changes in synaptic dopamine

    SciTech Connect

    Gifford, A.N.; Gatley, S.J.; Shea, C.

    1996-05-01

    Prior studies have shown that the in vivo binding of D2 radioligands such as raclopride and IBZM is subject to competition with synaptic DA. D2 radioligands can thus be used to evaluate both direct effects of drugs at DAergic synapses, and indirect effects at these synapses mediated via neurotransmitter interactions. Competition with DA must also be a potential confounding factor in studies designed to evaluate changes in D2 receptor number. We evaluated the sensitivity of the D1 radioligands for susceptibility to alterations in synaptic DA. We evaluated the sensitivity of the D1 radioligand SCH 23390 using three different models: rat brain slices in which DA release is controlled by electrically simulation, ex vivo mouse brain uptake, and PET in the baboon brain. In slices, the order of sensitivity of DA system radioligands to synaptic DA was D1>D2>DA transporter, and the sensitivity of the low affinity (Kd = 1 nM) D2 ligand, [H-3]raclopride, was greater than that of the high affinity (Kd = 0.05 nM) D2 ligand, [I-123]epidepride (Gifford et al., Synapse, in press). In mice, striatal [H-3]SCH 23390 was decreased after administration of the DA transporter blocker RTI-55 ({beta}-CIT, 0.5 mg/kg, i/v), to a similar extent as that of co-administered [I-123]epidepride. In these experiments RTI-55 was given four hours after injection of radiotracers, after peak striatal radioactivity, to avoid the effects of the increase in delivery of radiotracer to the brain caused by RTI-55. In PET experiments, striatal binding of the D1 radioligand [C-11]SCH23390 was less sensitive to challenge with the DA transporter blocker methylphenidate (0.5 mg/kg, 7-10 min before radiotracer) than is [C-11]raclopride. Our results together indicate that SCH 23390 is not very sensitive to pharmacological challenges which decrease the in vivo binding of labeled raclopride.

  15. Measurements of d2n and A1n: Probing the neutron spin structure

    DOE PAGES

    Flay, D.; Posik, M.; Parno, D. S.; ...

    2016-09-06

    We report on the results of the E06-014 experiment performed at Jefferson Lab in Hall A, where a precision measurement of the twist-3 matrix elementmore » $$d_2$$ of the neutron ($$d_{2}^{n}$$) was conducted. This quantity represents the average color Lorentz force a struck quark experiences in a deep inelastic electron scattering event off a neutron due to its interaction with the hadronizing remnants. This color force was determined from a linear combination of the third moments of the spin structure functions $$g_1$$ and $$g_2$$ on $$^{3}$$He after nuclear corrections had been applied to these moments. The kinematics included two average $$Q^{2}$$ bins of $3.2$ GeV$$^{2}$$ and $4.3$ GeV$$^{2}$$, and Bjorken-$x$ $$0.25 \\leq x \\leq 0.90$$ covering the DIS and resonance regions. We found $$d_2^n$$ to be small and negative for $ = 3.2$ GeV$$^{2}$$, and smaller for $ = 4.3$ GeV$$^{2}$$, consistent with a lattice QCD calculation. The twist-4 matrix element $$f_{2}^{n}$$ was extracted by combining our $$d_{2}^{n}$$ with the world data on $$\\Gamma_{1}^{n} = \\int_{0}^{1} g_{1}^{n} dx$$. We found $$f_{2}^{n}$$ to be roughly an order of magnitude larger than $$d_{2}^{n}$$. Utilizing the extracted $$d_{2}^{n}$$ and $$f_{2}^{n}$$ data, we separated the color force into its electric and magnetic components, $$F_{E}^{y,n}$$ and $$F_{B}^{y,n}$$, and found them to be equal and opposite in magnitude, in agreement with instanton model predictions but not with those from QCD sum rules. Additionally, we have extracted the neutron virtual photon-nucleon asymmetry $$A_{1}^{n}$$, the structure function ratio $$g_{1}^{n}/F_{1}^{n}$$, and the quark ratios $$(\\Delta u + \\Delta \\bar{u})/(u + \\bar{u})$$ and $$(\\Delta d + \\Delta \\bar{d})/(d + \\bar{d})$$. Lastly, these results were found to be consistent with DIS world data and with the prediction of the constituent quark model but at odds with those of perturbative QCD at large $x$.« less

  16. Functional Characterisation of Eel Dopamine D2 Receptors and Involvement in the Direct Inhibition of Pituitary Gonadotrophins.

    PubMed

    Jolly, C; Rousseau, K; Prézeau, L; Vol, C; Tomkiewicz, J; Dufour, S; Pasqualini, C

    2016-09-01

    In various vertebrate species, dopamine (DA) exerts an inhibitory action on reproduction. In the European eel, DA plays a pivotal role in the inhibitory control of gonadotroph function and the blockade of puberty. In vivo studies have suggested that this effect is mediated by receptors pharmacologically related to the D2 family. In the European eel, two distinct D2 receptor (D2-R) paralogous genes have been identified (D2A-R and D2B-R) and both were shown to be expressed in the pituitary. We investigated the potential role of each paralogue in the control of gonadotroph function in this species. Eel recombinant D2A-R or D2B-R were expressed in HEK 293 cells, with a universal Gα subunit, and receptor activation was followed by inositol phosphate production. Recombinant D2-Rs exhibited a comparable affinity for DA, although they had differential affinities for mammalian D2-R agonists and antagonists, supporting subtle structure/activity differences. Furthermore, using eel pituitary cell primary cultures, the expression by gonadotroph cells of both native eel D2-R paralogues was examined by in situ hybridisation of D2A-R or D2B-R transcripts, coupled with immunofluorescence of luteinising hormone (LH)β or follicle-stimulating (FSH)β. LH and to a lesser extent, FSH cells expressed both D2-R transcripts but with a clear predominance of D2B-R. Notably, D2B-R transcripts were detected for the majority of LH cells. Accordingly, using these cultures, we showed that DA potently inhibited basal and testosterone-stimulated LHβ expression and less potently basal and activin-stimulated FSHβ expression. We also tested some D2-R antagonists, aiming to select the most adequate one to be used in innovative protocols for induction of eel sexual maturation. We identified eticlopride as the most potent inhibitor of DA action on basal and stimulated LH expression in vitro. Our data suggest a differential functionalisation of the duplicated receptor genes and demonstrate that

  17. Absolute cross sections for dissociative electron attachment to H2O and D2O

    NASA Astrophysics Data System (ADS)

    Rawat, Prashant; Prabhudesai, Vaibhav S.; Aravind, G.; Rahman, M. A.; Krishnakumar, E.

    2007-12-01

    The dissociative electron attachment (DEA) process to water (H2O) and heavy water (D2O) has been studied in the gas phase in a cross beam experiment for electron energies up to 20 eV. The apparatus used eliminates discrimination due to the kinetic energy and angular distribution of the ions. The cross sections are normalized to absolute values using the cross section for production of O- from O2 (Rapp and Briglia 1965 J. Chem. Phys. 43 1480). These are the first exhaustive measurements of absolute cross sections for both the H- and O- from H2O and D- and O- from D2O at all the three resonances. The results are compared with the scarce data available in the literature. Isotope effect is observed at the 12 eV resonance in the H- channel and at all the three resonances in the O- channel.

  18. Production of Excited Atomic Hydrogen and Deuterium from H2, D2 and HD Photodissociation

    NASA Astrophysics Data System (ADS)

    Machacek, J. R.; Andrianarijaona, V. M.; Furst, J. E.; Gay, T. J.; Kilcoyne, A. L. D.; Landers, A. L.; McLaughlin, K. W.

    2009-10-01

    We have measured the production of Lyα and Hα fluorescence from atomic H and D resulting from the photodissociation of H2, D2 and HD by linearly-polarized photons with energies between 20 and 65 eV. In this energy range, excited photofragments result primarily from the production of doubly-excited molecular species which promptly autoionize or dissociate into two neutrals. Comparison between the relative cross sections of H2 and D2 and the available theory show only qualitative agreement. We will discuss the various systematic effects which affect this and other types of synchrotron-based measurements in this energy range. Support provided by the NSF (Grant PHY-0653379), DOE (LBNL/ALS) and ANSTO (Access to Major Research Facilities Programme).

  19. Exact spectra of strong coulomb correlations of 3-D 2-e harmonic dots in magnetic field

    NASA Astrophysics Data System (ADS)

    Aggarwal, Priyanka; Sharma, Shivalika; Kaur, Harsimran; Singh, Sunny; Hazra, Ram Kuntal

    2017-01-01

    Applications of 3-D 2-e systems have proliferated very fast due to technological advancements in wide range of phenomena from atomic landscape to mesoscopic scale. The unusual properties of atomic/mesoscopic systems are the results of interplaying charge interactions among different bound states. The non-trivial e-e correlations in electrically and/or magnetically confined systems improvise wealth of intriguing challenges at fundamental level due to lack of exact solution of Schrödinger equations. For the first time, a novel methodology of exactly finite summed coulomb correlations invented by us is so handy that even usual programmable calculator can be used to examine the electronic structures of 3-D 2-e harmonic dots in perpendicular magnetic field (symmetric gauge). Statistics of electronic levels, heat capacity measurements and magnetization (T∼1 K) are also investigated in brief to probe the degree of disorderedness.

  20. Does prostaglandin D2 hold the cure to male pattern baldness?

    PubMed

    Nieves, Ashley; Garza, Luis A

    2014-04-01

    Lipids in the skin are the most diverse in the entire human body. Their bioactivity in health and disease is underexplored. Prostaglandin D2 has recently been identified as a factor which is elevated in the bald scalp of men with androgenetic alopecia (AGA) and has the capacity to decrease hair lengthening. An enzyme which synthesizes it, prostaglandin D2 synthase (PTGDS or lipocalin-PGDS), is hormone responsive in multiple other organs. PGD2 has two known receptors, GPR44 and PTGDR. GPR44 was found to be necessary for the decrease in hair growth by PGD2 . This creates an exciting opportunity to perhaps create novel treatments for AGA, which inhibit the activity of PTGDS, PGD2 or GPR44. This review discusses the current knowledge surrounding PGD2 , and future steps needed to translate these findings into novel therapies for patients with AGA.

  1. Successful treatment of dopamine dysregulation syndrome with dopamine D2 partial agonist antipsychotic drug.

    PubMed

    Mizushima, Jin; Takahata, Keisuke; Kawashima, Noriko; Kato, Motoichiro

    2012-07-07

    Dopamine dysregulation syndrome (DDS) consists of a series of complications such as compulsive use of dopaminergic medications, aggressive or hypomanic behaviors during excessive use, and withdrawal states characterized by dysphoria and anxiety, caused by long-term dopaminergic treatment in patients with Parkinson's disease (PD). Although several ways to manage DDS have been suggested, there has been no established treatment that can manage DDS without deterioration of motor symptoms. In this article, we present a case of PD in whom the administration of the dopamine D2 partial agonistic antipsychotic drug aripiprazole improved DDS symptoms such as craving and compulsive behavior without worsening of motor symptoms. Considering the profile of this drug as a partial agonist at D2 receptors, it is possible that it exerts its therapeutic effect on DDS by modulating the dysfunctional dopamine system.

  2. Lack of association between dopamine D2 receptor gene Cys311 variant and schizophrenia

    SciTech Connect

    Tanaka, Toshihisa; Fukushima, Noboru; Takahashi, Makoto; Kameda, Kensuke; Ihda, Shin

    1996-04-09

    Itokawa et al. reported identifying one missense nucleotide mutation from C to G resulting in a substitution of serine with cysteine at codon 311 in the third intracellular loop of the dopamine D2 receptor in schizophrenics. Arinami et al. reported finding a positive association between the Cys311 variant and schizophrenia. In response to the report by Arinami et al. we examined 106 unrelated Japanese schizophrenics and 106 normal controls to determine if there is any association of the Cys311 variant with schizophrenia. However, we found no statistically significant differences in allelic frequencies of Cys311 between schizophrenia and normal controls. The present results as well as those of all previous studies except for that of Arinami et al. indicated that an association between the dopamine D2 receptor gene and schizophrenia is unlikely to exist. 24 refs., 1 fig., 1 tab.

  3. 3D/2D image registration: the impact of X-ray views and their number.

    PubMed

    Tomazevic, Dejan; Likar, Bostjan; Pernus, Franjo

    2007-01-01

    An important part of image-guided radiation therapy or surgery is registration of a three-dimensional (3D) preoperative image to two-dimensional (2D) images of the patient. It is expected that the accuracy and robustness of a 3D/2D image registration method do not depend solely on the registration method itself but also on the number and projections (views) of intraoperative images. In this study, we systematically investigate these factors by using registered image data, comprising of CT and X-ray images of a cadaveric lumbar spine phantom and the recently proposed 3D/2D registration method. The results indicate that the proportion of successful registrations (robustness) significantly increases when more X-ray images are used for registration.

  4. Correspondenceless 3D-2D registration based on expectation conditional maximization

    NASA Astrophysics Data System (ADS)

    Kang, X.; Taylor, R. H.; Armand, M.; Otake, Y.; Yau, W. P.; Cheung, P. Y. S.; Hu, Y.

    2011-03-01

    3D-2D registration is a fundamental task in image guided interventions. Due to the physics of the X-ray imaging, however, traditional point based methods meet new challenges, where the local point features are indistinguishable, creating difficulties in establishing correspondence between 2D image feature points and 3D model points. In this paper, we propose a novel method to accomplish 3D-2D registration without known correspondences. Given a set of 3D and 2D unmatched points, this is achieved by introducing correspondence probabilities that we model as a mixture model. By casting it into the expectation conditional maximization framework, without establishing one-to-one point correspondences, we can iteratively refine the registration parameters. The method has been tested on 100 real X-ray images. The experiments showed that the proposed method accurately estimated the rotations (< 1°) and in-plane (X-Y plane) translations (< 1 mm).

  5. "Gold standard" data for evaluation and comparison of 3D/2D registration methods.

    PubMed

    Tomazevic, Dejan; Likar, Bostjan; Pernus, Franjo

    2004-01-01

    Evaluation and comparison of registration techniques for image-guided surgery is an important problem that has received little attention in the literature. In this paper we address the challenging problem of generating reliable "gold standard" data for use in evaluating the accuracy of 3D/2D registrations. We have devised a cadaveric lumbar spine phantom with fiducial markers and established highly accurate correspondences between 3D CT and MR images and 18 2D X-ray images. The expected target registration errors for target points on the pedicles are less than 0.26 mm for CT-to-X-ray registration and less than 0.42 mm for MR-to-X-ray registration. As such, the "gold standard" data, which has been made publicly available on the Internet (http://lit.fe.uni-lj.si/Downloads/downloads.asp), is useful for evaluation and comparison of 3D/2D image registration methods.

  6. Sieving of H2 and D2 Through End-to-End Nanotubes

    NASA Astrophysics Data System (ADS)

    Devagnik, Dasgupta; Debra, J. Searles; Lamberto, Rondoni; Stefano, Bernardi

    2014-10-01

    We study the quantum molecular sieving of H2 and D2 through two nanotubes placed end-to-end. An analytic treatment, assuming that the particles have classical motion along the axis of the nanotube and are confined in a potential well in the radial direction, is considered. Using this idealistic model, and under certain conditions, it is found that this device can act as a complete sieve, allowing chemically pure deuterium to be isolated from an isotope mixture. We also consider a more realistic model of two carbon nanotubes and carry out molecular dynamics simulations using a Feynman—Hibbs potential to model the quantum effects on the dynamics of H2 and D2. Sieving is also observed in this case, but is caused by a different process.

  7. Reliability of the dynavision™ d2 for assessing reaction time performance.

    PubMed

    Wells, Adam J; Hoffman, Jay R; Beyer, Kyle S; Jajtner, Adam R; Gonzalez, Adam M; Townsend, Jeremy R; Mangine, Gerald T; Robinson, Edward H; McCormack, William P; Fragala, Maren S; Stout, Jeffrey R

    2014-01-01

    Recently, the Dynavision™ D2 Visuomotor Training Device (D2) has emerged as a tool in the assessment of reaction time (RT); however, information regarding the reliability of the D2 have been limited, and to date, reliability data have been limited to non- generalizable samples. Therefore, the purpose of this study was to establish intraclass correlation coefficients (ICC2,1) for the D2 that are generalizable across a population of recreationally active young adults. Forty-two recreationally active men and women (age: 23.41 ± 4.84 years; height: 1.72 ± 0.11 m; mass: 76.62 ± 18.26 Kg) completed 6 trials for three RT tasks of increasing complexity. Each trial was separated by at least 48-hours. A repeated measures ANOVA was used to detect differences in performance across the six trials. Intraclass correlation coefficients (ICC2,1) standard error of measurement (SEM), and minimal differences (MD) were used to determine the reliability of the D2 from the two sessions with the least significant difference score. Moderate to strong reliability was demonstrated for visual RT (ICC2,1: 0.84, SEM: 0.033), and reactive ability in both Mode A and Mode B tasks (Mode A hits: ICC2,1: 0.75, SEM: 5.44; Mode B hits: ICC2,1: 0.73, SEM: 8.57). Motor RT (ICC2,1: 0.63, SEM: 0.035s) showed fair reliability, while average RT per hit for Modes A and B showed moderate reliability (ICC2,1: 0.68, SEM: 0.43 s and ICC2,1: 0.72, SEM: 0.03 s respectively). It appears that one familiarization trial is necessary for the choice reaction time (CRT) task while three familiarization trials are necessary for reactive RT tasks. In conclusion, results indicate that the Dynavision™ D2 is a reliable device to assess neuromuscular reactivity given that an adequate practice is provided. The data presented are generalizable to a population of recreationally active young adults. Key PointsThe Dynavision™ D2 is a light-training reaction device, developed to train sensory motor integration through the

  8. M2 to D2 and vice versa by 3-Lie and Lie bialgebra

    NASA Astrophysics Data System (ADS)

    Aali-Javanangrouh, M.; Rezaei-Aghdam, A.

    2016-11-01

    Using the concept of a 3-Lie bialgebra, which has recently been defined in arXiv:1604.04475, we construct a Bagger-Lambert-Gustavson (BLG) model for the M2-brane on a Manin triple of a special 3-Lie bialgebra. Then by using the correspondence and the relation between those 3-Lie bialgebra with Lie bialgebra, we reduce this model to an N=(4,4) WZW model (D2-brane), such that its algebraic structure is a Lie bialgebra with one 2-cocycle. In this manner by using the correspondence of the 3-Lie bialgebra and Lie bialgebra (for this special 3-Lie algebra) one can construct the M2-brane from a D2-brane and vice versa.

  9. Synthesis of 1-O-(2'-acetoxy)benzoyl-alpha-D-2-deoxyglucopyranose, a novel aspirin prodrug.

    PubMed

    Truelove, J E; Hussain, A A; Kostenbauder, H B

    1980-02-01

    The synthesis and characterization of 1-O-(2'-acetoxy)benzoyl-alpha-D-2-deoxyglucopyranose, a novel aspirin prodrug, are described. 3,4,6-Tri-O-benzyl-alpha-D-2-deoxyglucopyranose was synthesized by methylating the anomeric hydroxyl group of 2-deoxyglucose, benzylating the 3-, 4-, and 6-hydroxy functional grups, and cleaving hydrolytically the anomeric methyl group. Reaction of the tribenzylated sugar with the acid chloride of aspirin and subsequent hydrogenolysis of the benzyl groups resulted in the prodrug, mp 128 degrees. The compound was further characterized by elemental analysis and PMR and 13C-NMR spectroscopy. In vitro, the compound cleaved to aspirin with a half-life of 7 min at 37 degrees. Prodrug cleavage was independent of pH over the pH 3--9 range.

  10. Serotonergic agonists behave as partial agonists at the dopamine D2 receptor.

    PubMed

    Rinken, A; Ferré, S; Terasmaa, A; Owman, C; Fuxe, K

    1999-02-25

    RAT dopamine D2short receptors expressed in CHO cells were characterized by activation of [35S]GTPgammaS binding. There were no significant differences between the maximal effects seen in activation of [35S]GTPgammaS binding caused by dopaminergic agonists, but the effects of 5-HT, 8OH-DPAT and 5-methoxytryptamine amounted to 47 +/- 7%, 43 +/- 5% and 70 +/- 7% of the dopamine effect, respectively. The dopaminergic antagonist (+)butaclamol inhibited activations of both types of ligands with equal potency (pA2 = 8.9 +/- 0.1), indicating that only one type of receptor is involved. In competition with [3H]raclopride binding, dopaminergic agonists showed 53 +/- 2% of the binding sites in the GTP-dependent high-affinity state, whereas 5-HT showed only 20 +/- 3%. Taken together, the results indicate that serotonergic agonists behave as typical partial agonists for D2 receptors with potential antiparkinsonian activity.

  11. Induced IR overtone and fundamental bands of isotopic H 2 molecules adsorbed in NaCaA zeolites

    NASA Astrophysics Data System (ADS)

    Förster, H.; Frede, W.

    1984-05-01

    NIR spectroscopy has been successfully applied to surface chemical problems, using the FT transmission technique. Vibrational spectra of H 2 and D 2, adsorbed in NaA and NaCaA zeolites, have been recorded in the fundamental regions of both adsorbates and, for the first time, in the overtone region of D 2. Useful information on the properties of the adsorbed molecules can be derived from the overtone spectra of D 2 and the fine structure of the H 2 fundamental. It turns out that the properties of the D 2 molecules, e.g. dissociation energy and anharmonicity, are hardly affected by adsorption. The fine structure of the H 2 fundamental, however, indicates the rotation to be strongly hindered. The ortho-para splitting is decreased with respect to the free molecule value and approaches that for planarly rotating molecules. Due to this hindrance, the corresponding D 2 splitting is not resolved.

  12. D2 receptor block abolishes θ burst stimulation-induced neuroplasticity in the human motor cortex.

    PubMed

    Monte-Silva, Katia; Ruge, Diane; Teo, James T; Paulus, Walter; Rothwell, John C; Nitsche, Michael A

    2011-09-01

    Dopamine (DA) is a neurotransmitter with an important influence on learning and memory, which is thought to be due to its modulatory effect on plasticity at central synapses, which in turn depends on activation of D1 and D2 receptors. Methods of brain stimulation (transcranial direct current stimulation, tDCS; paired associative stimulation, PAS) lead to after-effects on cortical excitability that are thought to resemble long-term potentization (LTP)/long-term depression (LTD) in reduced preparations. In a previous study we found that block of D2 receptors abolished plasticity induced by tDCS but had no effect on the facilitatory plasticity induced by PAS. We postulated that the different effect of D2 receptor block on tDCS- and PAS-induced plasticity may be due to the different focality and associativity of the stimulation techniques. However, alternative explanations for this difference could not be ruled out. tDCS also differs from PAS in other aspects, as tDCS induces plasticity by subthreshold neuronal activation, modulating spontaneous activity, whereas PAS induces plasticity via phasic suprathreshold stimulation. The present study in 12 volunteers examined effects of D2 receptor blockade (sulpiride (SULP) 400 mg), on the LTP/LTD-like effects of theta burst transcranial magnetic stimulation (TBS), which has less restricted effects on cortical synapses than that of PAS, and does not induce associative plasticity, similar to tDCS, but on the other hand induces cortical excitability shifts by suprathreshold (rhythmic) activation of cortical neurons similarly to PAS. Administration of SULP blocked both the excitatory and inhibitory effects of intermittent (iTBS) and continuous TBS (cTBS), respectively. As the reduced response to TBS following SULP resembles its effect on tDCS, the results support an effect of DA on plasticity, which might be related to the focality and associativity of the plasticity induced.

  13. A faster method for 3D/2D medical image registration—a simulation study

    NASA Astrophysics Data System (ADS)

    Birkfellner, Wolfgang; Wirth, Joachim; Burgstaller, Wolfgang; Baumann, Bernard; Staedele, Harald; Hammer, Beat; Claudius Gellrich, Niels; Jacob, Augustinus Ludwig; Regazzoni, Pietro; Messmer, Peter

    2003-08-01

    3D/2D patient-to-computed-tomography (CT) registration is a method to determine a transformation that maps two coordinate systems by comparing a projection image rendered from CT to a real projection image. Iterative variation of the CT's position between rendering steps finally leads to exact registration. Applications include exact patient positioning in radiation therapy, calibration of surgical robots, and pose estimation in computer-aided surgery. One of the problems associated with 3D/2D registration is the fact that finding a registration includes solving a minimization problem in six degrees of freedom (dof) in motion. This results in considerable time requirements since for each iteration step at least one volume rendering has to be computed. We show that by choosing an appropriate world coordinate system and by applying a 2D/2D registration method in each iteration step, the number of iterations can be grossly reduced from n6 to n5. Here, n is the number of discrete variations around a given coordinate. Depending on the configuration of the optimization algorithm, this reduces the total number of iterations necessary to at least 1/3 of it's original value. The method was implemented and extensively tested on simulated x-ray images of a tibia, a pelvis and a skull base. When using one projective image and a discrete full parameter space search for solving the optimization problem, average accuracy was found to be 1.0 +/- 0.6(°) and 4.1 +/- 1.9 (mm) for a registration in six parameters, and 1.0 +/- 0.7(°) and 4.2 +/- 1.6 (mm) when using the 5 + 1 dof method described in this paper. Time requirements were reduced by a factor 3.1. We conclude that this hardware-independent optimization of 3D/2D registration is a step towards increasing the acceptance of this promising method for a wide number of clinical applications.

  14. Reduced striatal dopamine DA D2 receptor function in dominant-negative GSK-3 transgenic mice.

    PubMed

    Gomez-Sintes, Raquel; Bortolozzi, Analia; Artigas, Francesc; Lucas, José J

    2014-09-01

    Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase with constitutive activity involved in cellular architecture, gene expression, cell proliferation, fate decision and apoptosis, among others. GSK-3 expression is particularly high in brain where it may be involved in neurological and psychiatric disorders such as Alzheimer׳s disease, bipolar disorder and major depression. A link with schizophrenia is suggested by the antipsychotic drug-induced GSK-3 regulation and by the involvement of the Akt/GSK-3 pathway in dopaminergic neurotransmission. Taking advantage of the previous development of dominant negative GSK-3 transgenic mice (Tg) showing a selective reduction of GSK-3 activity in forebrain neurons but not in dopaminergic neurons, we explored the relationship between GSK-3 and dopaminergic neurotransmission in vivo. In microdialysis experiments, local quinpirole (DA D2-R agonist) in dorsal striatum reduced dopamine (DA) release significantly less in Tg mice than in wild-type (WT) mice. However, local SKF-81297 (selective DA D1-R agonist) in dorsal striatum reduced DA release equally in both control and Tg mice indicating a comparable function of DA D1-R in the direct striato-nigral pathway. Likewise, systemic quinpirole administration - acting preferentially on presynaptic DA D2- autoreceptors to modulate DA release-reduced striatal DA release similarly in both control and Tg mice. Quinpirole reduced locomotor activity and induced c-fos expression in globus pallidus (both striatal DA D2-R-mediated effects) significantly more in WT than in Tg mice. Taking together, the present results show that dominant negative GSK-3 transgenic mice show reduced DA D2-R-mediated function in striatum and further support a link between dopaminergic neurotransmission and GSK-3 activity.

  15. Activation process and absorption/desorption of D2O for Zr-V-Fe getter

    NASA Astrophysics Data System (ADS)

    Ichimura, K.; Inoue, N.; Ashida, K.; Watanabe, K.; Takeuchi, T.

    1984-12-01

    Nonevaporable getters have wide applicability for tritium handling systems. From this view point, the activation process of the Zr-V-Fe getter (St-707) and absorption/desorption of D2O on the getter surface were investigated, by means of XPS-SIMS and mass analyzed thermal desorption spectroscopy. XPS-SIMS measurements revealed that the getter surface exposed to air was covered with adsorbed H2O, CO and small amounts of hydrocarbons and that the getter components are oxidized. Upon heating of the getter above 500 °C, the adsorbed species disappeared from the surface, partly due to desorption and partly due to migration into the bulk. Consequently, metallic Zr and V appeared on the surface, whereas Fe disappeared. The surface composition was evaluated to be 87 at% Zr-13 at% V. After the activation, water (D2O ) was readily absorbed into the getter at 300 °C in the form of deuterium atoms. The absorption rate was proportional to the partial pressure of water, indicating that the rate determining step for the absorption is the dissociation of water molecules on the surface. The absorption rate constant was 0.009 and 0.24 cc/s/cm2 (net surface area) [or 1.5 and 39 cc/s/cm2 (projected area)] at 25 and 300°C, respectively. Only D2 was desorbed from the getter exposed to D2O at 25 and 300 °C. The rate determining step for the desorption is association of deuterium atoms on the surface diffused from the bulk.

  16. D2-brane as the wormhole and the number of the universes

    NASA Astrophysics Data System (ADS)

    Gusin, Paweł

    2016-02-01

    We construct wormhole-like solutions in type IIA string theory. These solutions represent wormholes in four dimensions and are given by the D2-branes within appropriated backgrounds fields. We present the conditions on these fields which lead to the four-dimensional wormholes. In the special case, we show how the particular solution in type IIA theory leads to the dynamic wormhole. We also speculate about the number of universes and the cosmological constant.

  17. Complete Measurement of S(1D2) Photofragment Alignment from Abel-Invertible Ion Images

    NASA Astrophysics Data System (ADS)

    Rakitzis, T. Peter; Samartzis, Peter C.; Kitsopoulos, Theofanis N.

    2001-09-01

    A novel method to measure directly the photofragment alignment from Abel-invertible two-dimensional ion images, as a function of photofragment recoil velocity, is demonstrated for S(1D2) atoms from the photodissociation of carbonyl sulfide at 223 nm. The results are analyzed in terms of coherent and incoherent contributions from two dissociative states, showing that the phase differences of the asymptotic wave functions of the fast and slow recoil-velocity channel are approximately π/2 and 0, respectively.

  18. Mode structure in an optically pumped D2O far-infrared ring laser

    NASA Astrophysics Data System (ADS)

    Yuan, D. C.; Soumagne, G.; Siegrist, M. R.

    1990-02-01

    The mode structures in an optically pumped D2O far-infrared ring laser and a corresponding linear resonator have been compared. While single-mode operation can be obtained over the whole useful pressure range in the ring structure, this is only possible at pressures greater than 8 torr in the linear resonator case. A numerical model predicts quite well the pulse shape, pressure dependence, and influence of the resonator quality in the ring cavity.

  19. Characterization of dopamine D1 and D2 receptor-expressing neurons in the mouse hippocampus.

    PubMed

    Gangarossa, Giuseppe; Longueville, Sophie; De Bundel, Dimitri; Perroy, Julie; Hervé, Denis; Girault, Jean-Antoine; Valjent, Emmanuel

    2012-12-01

    The hippocampal formation is part of an anatomical system critically involved in learning and memory. Increasing evidence suggests that dopamine plays an important role in learning and memory as well as in several forms of synaptic plasticity. However, the precise identification of neuronal populations expressing D1 or D2 dopamine receptors within the hippocampus is still lacking. To clarify this issue, we used BAC transgenic mice expressing enhanced green fluorescent protein (EGFP) under the control of the promoter of dopamine D1 or D2 receptors. In Drd1a-EGFP mice, sparse GFP-expressing neurons were detected among glutamatergic projecting neurons of the granular layer of the dentate gyrus and GABAergic interneurons located in the hilus. A dense immunofluorescence was observed in the outer and medial part of the molecular layer of the dentate gyrus as well as in the inner part of the molecular layer of CA1 corresponding to the terminals of pyramidal neurons of the entorhinal cortex defining the perforant and the temporo-ammonic pathway respectively. Finally, scattered D1 receptor-expressing neurons were also identified as GABAergic interneurons in the CA3/CA1 fields of the hippocampus. In Drd2-EGFP transgenic mice, GFP was exclusively detected in the glutamatergic mossy cells located in the polymorphic layer of the dentate gyrus. This pattern was confirmed in Drd2-Cre mice crossed with NLS-LacZ-Tau(mGFP) :LoxP and RCE:LoxP reporter lines. Our results demonstrate that D1 and D2 receptor-expressing neurons are strictly segregated in the mouse hippocampus. By clarifying the identity of D1 and D2 receptor-expressing neurons in the hippocampus, this study establishes a basis for future investigations aiming at elucidating their roles in the hippocampal network.

  20. STS-55 Payload Specialist Schlegel collects fungi sample at SL-D2 Rack 1

    NASA Technical Reports Server (NTRS)

    1993-01-01

    STS-55 German Payload Specialist 2 Hans Schlegel, wearing lightweight headset, collects fungi sample while working at Spacelab Deutsche 2 (SL-D2) science module Rack 1 Work Bench. Schlegel is conducting these procedures in conjunction with the 'Fruiting Body Development of Fungi' experiment. Pieces of the experiment casing freefloat in the workstation.Schlegel represents the German Aerospace Research Establishment (DLR) on the 10-day spacelab mission.

  1. STS-55 Payload Specialist Schlegel collects fungi sample at SL-D2 Rack 1

    NASA Technical Reports Server (NTRS)

    1993-01-01

    STS-55 German Payload Specialist 2 Hans Schlegel, wearing lightweight headset, collects fungi sample while working at Spacelab Deutsche 2 (SL-D2) science module Rack 1 Work Bench. Schlegel is conducting these procedures in conjunction with the 'Fruiting Body Development of Fungi' experiment. Schlegel was one of two payload specialists representing the German Aerospace Research Establishment (DLR) on the 10-day spacelab mission.

  2. A faster method for 3D/2D medical image registration--a simulation study.

    PubMed

    Birkfellner, Wolfgang; Wirth, Joachim; Burgstaller, Wolfgang; Baumann, Bernard; Staedele, Harald; Hammer, Beat; Gellrich, Niels Claudius; Jacob, Augustinus Ludwig; Regazzoni, Pietro; Messmer, Peter

    2003-08-21

    3D/2D patient-to-computed-tomography (CT) registration is a method to determine a transformation that maps two coordinate systems by comparing a projection image rendered from CT to a real projection image. Iterative variation of the CT's position between rendering steps finally leads to exact registration. Applications include exact patient positioning in radiation therapy, calibration of surgical robots, and pose estimation in computer-aided surgery. One of the problems associated with 3D/2D registration is the fact that finding a registration includes solving a minimization problem in six degrees of freedom (dof) in motion. This results in considerable time requirements since for each iteration step at least one volume rendering has to be computed. We show that by choosing an appropriate world coordinate system and by applying a 2D/2D registration method in each iteration step, the number of iterations can be grossly reduced from n6 to n5. Here, n is the number of discrete variations around a given coordinate. Depending on the configuration of the optimization algorithm, this reduces the total number of iterations necessary to at least 1/3 of it's original value. The method was implemented and extensively tested on simulated x-ray images of a tibia, a pelvis and a skull base. When using one projective image and a discrete full parameter space search for solving the optimization problem, average accuracy was found to be 1.0 +/- 0.6(degrees) and 4.1 +/- 1.9 (mm) for a registration in six parameters, and 1.0 +/- 0.7(degrees) and 4.2 +/- 1.6 (mm) when using the 5 + 1 dof method described in this paper. Time requirements were reduced by a factor 3.1. We conclude that this hardware-independent optimization of 3D/2D registration is a step towards increasing the acceptance of this promising method for a wide number of clinical applications.

  3. 3D-2D registration of cerebral angiograms based on vessel directions and intensity gradients

    NASA Astrophysics Data System (ADS)

    Mitrovic, Uroš; Špiclin, Žiga; Štern, Darko; Markelj, Primož; Likar, Boštjan; Miloševic, Zoran; Pernuš, Franjo

    2012-02-01

    Endovascular treatment of cerebral aneurysms and arteriovenous malformations (AVM) involves navigation of a catheter through the femoral artery and vascular system to the site of pathology. Intra-interventional navigation is done under the guidance of one or at most two two-dimensional (2D) X-ray fluoroscopic images or 2D digital subtracted angiograms (DSA). Due to the projective nature of 2D images, the interventionist needs to mentally reconstruct the position of the catheter in respect to the three-dimensional (3D) patient vasculature, which is not a trivial task. By 3D-2D registration of pre-interventional 3D images like CTA, MRA or 3D-DSA and intra-interventional 2D images, intra-interventional tools such as catheters can be visualized on the 3D model of patient vasculature, allowing easier and faster navigation. Such a navigation may consequently lead to the reduction of total ionizing dose and delivered contrast medium. In the past, development and evaluation of 3D-2D registration methods for endovascular treatments received considerable attention. The main drawback of these methods is that they have to be initialized rather close to the correct position as they mostly have a rather small capture range. In this paper, a novel registration method that has a higher capture range and success rate is proposed. The proposed method and a state-of-the-art method were tested and evaluated on synthetic and clinical 3D-2D image-pairs. The results on both databases indicate that although the proposed method was slightly less accurate, it significantly outperformed the state-of-the-art 3D-2D registration method in terms of robustness measured by capture range and success rate.

  4. Single exposure of dopamine D1 antagonist prevents and D2 antagonist attenuates methylphenidate effect

    PubMed Central

    Claussen, Catherine M; Witte, Lindsey J; Dafny, Nachum

    2015-01-01

    Methylphenidate (MPD) is a readily prescribed drug for the treatment of attention deficit hyperactivity disorder (ADHD) and moreover is used illicitly by youths for its cognitive-enhancing effects and recreation. MPD exposure in rodents elicits increased locomotor activity. Repetitive MPD exposure leads to further augmentation of their locomotor activity. This behavioral response is referred to as behavioral sensitization. Behavioral sensitization is used as an experimental marker for a drug’s ability to elicit dependence. There is evidence that dopamine (DA) is a key player in the acute and chronic MPD effect; however, the role of DA in the effects elicited by MPD is still debated. The objective of this study was to investigate the role of D1 and/or D2 DA receptors in the acute and chronic effect of MPD on locomotor activity. The study lasted for 12 consecutive days. Seven groups of male Sprague Dawley® rats were used. A single D1 or D2 antagonist was given before and after acute and chronic MPD administration. Single injection of D1 DA antagonist was able to significantly attenuate the locomotor activity when given prior to the initial MPD exposure and after repetitive MPD exposure, while the D2 DA antagonist partially attenuated the locomotor activity only when given before the second MPD exposure. The results show the role, at least in part, of the D1 DA receptor in the mechanism of behavioral sensitization, whereas the D2 DA receptor only partially modulates the response to acute and chronic MPD. PMID:27186140

  5. On Differential Expressions with {delta}-Potential: Exceptional Case d 2l

    SciTech Connect

    Antonevich, A.

    2010-11-25

    The paper is devoted to the study of the formal differential expressions (-{Delta}){sup l}u+a{delta}u for arbitrary l(set-membership sign)N and the dimension of R{sup d} equal d = 2l. Approximations of the singular part by means of a family of rank-one operators are constructed and resolvent convergence of this family is investigated. It is demonstrated that the results are different from the case d{ne}2l.

  6. Nqrs Data for C10H8D2 (Subst. No. 1222)

    NASA Astrophysics Data System (ADS)

    Chihara, H.; Nakamura, N.

    This document is part of Subvolume A `Substances Containing Ag … C10H15' of Volume 48 `Nuclear Quadrupole Resonance Spectroscopy Data' of Landolt-Börnstein - Group III `Condensed Matter'. It contains an extract of Section `3.2 Data tables' of the Chapter `3 Nuclear quadrupole resonance data' providing the NQRS data for C10H8D2 (Subst. No. 1222)

  7. Nqrs Data for C10H6D2 (Subst. No. 1209)

    NASA Astrophysics Data System (ADS)

    Chihara, H.; Nakamura, N.

    This document is part of Subvolume A `Substances Containing Ag … C10H15' of Volume 48 `Nuclear Quadrupole Resonance Spectroscopy Data' of Landolt-Börnstein - Group III `Condensed Matter'. It contains an extract of Section `3.2 Data tables' of the Chapter `3 Nuclear quadrupole resonance data' providing the NQRS data for C10H6D2 (Subst. No. 1209)

  8. Two Ingredients for My Dinner with R2D2: Integration and Adjustable Autonomy

    DTIC Science & Technology

    2000-01-01

    robotics and multi-modal interface research; namely, how crucial integration of multiple modes of communication are for adjustable autonomy, which in...turn is crucial for having dinner with R2D2. Furthermore, we discuss how our multi- modal interface to autonomous robots addresses these issues by...tracking goals, allowing for both natural and mechanical modes of input, and how our robotic system adjusts itself to ensure that goals are achieved

  9. Vertical D4-D2-D0 Bound States on K3 Fibrations and Modularity

    NASA Astrophysics Data System (ADS)

    Bouchard, Vincent; Creutzig, Thomas; Diaconescu, Duiliu-Emanuel; Doran, Charles; Quigley, Callum; Sheshmani, Artan

    2017-03-01

    An explicit formula is derived for the generating function of vertical D4-D2-D0 bound states on smooth K3 fibered Calabi-Yau threefolds, generalizing previous results of Gholampour and Sheshmani. It is also shown that this formula satisfies strong modularity properties, as predicted by string theory. This leads to a new construction of vector valued modular forms which exhibit some of the features of a generalized Hecke transform.

  10. NCQ 298, a new selective iodinated salicylamide ligand for the labelling of dopamine D2 receptors.

    PubMed

    Hall, H; Högberg, T; Halldin, C; Köhler, C; Ström, P; Ross, S B; Larsson, S A; Farde, L

    1991-01-01

    NCQ 298 ((S)-3-iodo-N-[(l-ethyl-2-pyrrolidinyl)methyl]-5,6- dimethoxysalicylamide) has an iodine substituent. We have labelled NCQ 298 with 123I and 125I, and used the radioligands as tracers in receptor studies in vitro, in vivo in autoradiography and in SPECT studies on Cynomolgus monkeys. [125I]NCQ 298 bound in vitro to a single binding site with a KD = 19 pM. NCQ 298 has thus a 10-fold higher affinity for the dopamine D2 receptors than the corresponding des-5-methoxy compound FLA 961 (IBZM), previously used in SPECT studies. The binding of [125I]NCQ 298 was entirely reversible (T1/2 = 17.5 min at 37 degrees C). Autoradiographical studies in vitro on rat and monkey brain tissue sections showed a distinct binding in caudate-putamen, nucleus accumbens, substantia nigra, and in layer 5 of the cerebral cortex. In vivo binding studies in mice showed a ratio of 10 between [125I]NCQ 298 binding in striatum and cerebellum. Binding was displaced by the selective dopamine D2 receptor antagonist raclopride. In SPECT studies with [123I]NCQ 298 in two Cynomolgus monkeys, radioactivity accumulated in the basal ganglia. The measured striatum to cerebellum ratio was about 15 after 3 h. A monkey brain phantom was constructed for the determination of conversion factors from pixel events to actual radioactivity. The resulting, corrected striatum to cerebellum ratio obtained was 30. After administration of 12 mg raclo-pride to one of the monkeys there was a substantial decrease in striatal radioactivity. [125I]NCQ 298 is a suitable ligand for the labelling of dopamine D2 receptors in vitro and in vivo. The specific properties of [123I]NCQ 298 suggest that this compound is a useful ligand for quantitative SPECT studies of dopamine D2 receptors in man.

  11. Striatal D1 and D2 signaling differentially predict learning from positive and negative outcomes.

    PubMed

    Cox, Sylvia M L; Frank, Michael J; Larcher, Kevin; Fellows, Lesley K; Clark, Crystal A; Leyton, Marco; Dagher, Alain

    2015-04-01

    The extent to which we learn from positive and negative outcomes of decisions is modulated by the neurotransmitter dopamine. Dopamine neurons burst fire in response to unexpected rewards and pause following negative outcomes. This dual signaling mechanism is hypothesized to drive both approach and avoidance behavior. Here we test a prediction deriving from a computational reinforcement learning model, in which approach is mediated via activation of the direct cortico-striatal pathway due to striatal D1 receptor stimulation, while avoidance occurs via disinhibition of indirect pathway striatal neurons secondary to a reduction of D2 receptor stimulation. Using positron emission tomography with two separate radioligands, we demonstrate that individual differences in human approach and avoidance learning are predicted by variability in striatal D1 and D2 receptor binding, respectively. Moreover, transient dopamine precursor depletion improved learning from negative outcomes. These findings support a bidirectional modulatory role for striatal dopamine in reward and avoidance learning via segregated D1 and D2 cortico-striatal pathways.

  12. Quantum Dynamics Study of the Isotopic Effect on Capture Reactions: HD, D2 + CH3

    NASA Technical Reports Server (NTRS)

    Wang, Dunyou; Kwak, Dochan (Technical Monitor)

    2002-01-01

    Time-dependent wave-packet-propagation calculations are reported for the isotopic reactions, HD + CH3 and D2 + CH3, in six degrees of freedom and for zero total angular momentum. Initial state selected reaction probabilities for different initial rotational-vibrational states are presented in this study. This study shows that excitations of the HD(D2) enhances the reactivities; whereas the excitations of the CH3 umbrella mode have the opposite effects. This is consistent with the reaction of H2 + CH3. The comparison of these three isotopic reactions also shows the isotopic effects in the initial-state-selected reaction probabilities. The cumulative reaction probabilities (CRP) are obtained by summing over initial-state-selected reaction probabilities. The energy-shift approximation to account for the contribution of degrees of freedom missing in the six dimensionality calculation is employed to obtain approximate full-dimensional CRPs. The rate constant comparison shows H2 + CH3 reaction has the biggest reactivity, then HD + CH3, and D2 + CH3 has the smallest.

  13. Nicotinic and opioid receptor regulation of striatal dopamine D2-receptor mediated transmission

    PubMed Central

    Mamaligas, Aphroditi A.; Cai, Yuan; Ford, Christopher P.

    2016-01-01

    In addition to dopamine neuron firing, cholinergic interneurons (ChIs) regulate dopamine release in the striatum via presynaptic nicotinic receptors (nAChRs) on dopamine axon terminals. Synchronous activity of ChIs is necessary to evoke dopamine release through this pathway. The frequency-dependence of disynaptic nicotinic modulation has led to the hypothesis that nAChRs act as a high-pass filter in the dopaminergic microcircuit. Here, we used optogenetics to selectively stimulate either ChIs or dopamine terminals directly in the striatum. To measure the functional consequence of dopamine release, D2-receptor synaptic activity was assessed via virally overexpressed potassium channels (GIRK2) in medium spiny neurons (MSNs). We found that nicotinic-mediated dopamine release was blunted at higher frequencies because nAChRs exhibit prolonged desensitization after a single pulse of synchronous ChI activity. However, when dopamine neurons alone were stimulated, nAChRs had no effect at any frequency. We further assessed how opioid receptors modulate these two mechanisms of release. Bath application of the κ opioid receptor agonist U69593 decreased D2-receptor activation through both pathways, whereas the μ opioid receptor agonist DAMGO decreased D2-receptor activity only as a result of cholinergic-mediated dopamine release. Thus the release of dopamine can be independently modulated when driven by either dopamine neurons or cholinergic interneurons. PMID:27886263

  14. Some Nuclear Calculations of U-235-D2O Gaseous-Core Cavity Reactors

    NASA Technical Reports Server (NTRS)

    Ragsdale, Robert G.; Hyland, Robert E.

    1961-01-01

    The results of a multigroup, diffusion theory study of spherical gaseous-core cavity reactors are presented in this report. The reactor cavity of gaseous U235 is enclosed by a region of hydrogen gas and is separated from an external D2O moderator-reflector by a zirconium structural shell. Some cylindrical reactors are also investigated. A parametric study of spherical reactors indicates that, for the range of variables studied, critical mass increases as: (1) Fuel region is compressed within the reactor cavity, (2) moderator thickness is decreased, (3) structural shell thickness is increased, and (4) moderator temperature is increased. A buckling analogy is used to estimate the critical mass of fully reflected cylindrical reactors from spherical results without fuel compression. For a reactor cavity of a 120-centimeter radius uniformly filled with fuel, no structural shell, a moderator temperature of 70 F, and a moderator thickness of 100 centimeters, the critical mass of a spherical reactor is 3.1 kilograms while that of a cylinder with a length-to-diameter ratio of 1.0 (L/D = 1) is approximately 3.8 kilograms and, with L/D = 2, 5.9 kilograms. For the range of variables considered for U235-D2O gaseous-core cavity reactors, the systems are characterized by 95 to 99 percent thermal absorptions, with the flux reaching a maximum in the moderator about 10 to 15 centimeters from the reactor cavity.

  15. Search for cold fusion using Pd-D2O cells and Ti-D mixtures

    NASA Astrophysics Data System (ADS)

    Hill, John C.; Stassis, C.; Shinar, J.; Goldman, A. I.; Folkerts, R.; Schwellenbach, D. D.; Peterson, D. T.; Widrig, C.; Porter, M.; Benesh, C. J.; Vary, J. P.

    1990-09-01

    We have searched for cold fusion produced in an electrolytic cell with Pd cathode and Pt anode. The electrolyte was 0.1 molar LiOD in 99.8% D2O. A 2-mm rod of polycrystalline Pd and a 4-mm rod of single crystal Pd were used. No radiation was detected above background by a BF3 neutron and Ge γ-X detector. The D2 loading of the Pd was 0.8 D per Pd atom reaching saturation after 4 hours. We also attempted to duplicate the work of Scaramuzzi and co-workers on the Ti-D2 system. Both powder and pieces of Ti were used. The material was cycled several times between 1100 K and 77 K. No neutron, γ- or x-ray emission above background was observed. The results of a barrier penetration calculation for H-like atoms are presented. The high fusion rates reported for PdD x . are much larger than those expected from theoretical calculations on these systems.

  16. Involvement of GluD2 in Fear-Conditioned Bradycardia in Mice

    PubMed Central

    Kotajima-Murakami, Hiroko; Narumi, Sakae; Yuzaki, Michisuke; Yanagihara, Dai

    2016-01-01

    Lesions in the cerebellar vermis abolish acquisition of fear-conditioned bradycardia in animals and human patients. The δ2 glutamate receptor (GluD2) is predominantly expressed in cerebellar Purkinje cells. The mouse mutant ho15J carries a spontaneous mutation in GluD2 and these mice show a primary deficiency in parallel fiber-Purkinje cell synapses, multiple innervations of Purkinje cells by climbing fibers, and impairment of long-term depression. In the present study, we used ho15J mice to investigate the role of the cerebellum in fear-conditioned bradycardia. We recorded changes in heart rate of ho15J mice induced by repeated pairing of an acoustic (conditioned) stimulus (CS) with an aversive (unconditioned) stimulus (US). The mice acquired conditioned bradycardia on Day 1 of the CS-US phase, similarly to wild-type mice. However, the magnitude of the conditioned bradycardia was not stable in the mutant mice, but rather was exaggerated on Days 2–5 of the CS-US phase. We examined the effects of reversibly inactivating the cerebellum by injection of an antagonist against the α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor (AMPAR). The antagonist abolished expression of conditioned responses in both wild-type and ho15J mice. We conclude that the GluD2 mutation in the ho15J mice affects stable retention of the acquired conditioned bradycardia. PMID:27820843

  17. Spatial reorganization of putaminal dopamine D2-like receptors in cranial and hand dystonia.

    PubMed

    Black, Kevin J; Snyder, Abraham Z; Mink, Jonathan W; Tolia, Veeral N; Revilla, Fredy J; Moerlein, Stephen M; Perlmutter, Joel S

    2014-01-01

    The putamen has a somatotopic organization of neurons identified by correspondence of firing rates with selected body part movements, as well as by complex, but organized, differential cortical projections onto putamen. In isolated focal dystonia, whole putaminal binding of dopamine D2-like receptor radioligands is quantitatively decreased, but it has not been known whether selected parts of the putamen are differentially affected depending upon the body part affected by dystonia. The radioligand [(18)F]spiperone binds predominantly to D2-like receptors in striatum. We hypothesized that the spatial location of [(18)F]spiperone binding within the putamen would differ in patients with dystonia limited to the hand versus the face, and we tested that hypothesis using positron emission tomography and magnetic resonance imaging. To address statistical and methodological concerns, we chose a straightforward but robust image analysis method. An automated algorithm located the peak location of [(18)F]spiperone binding within the striatum, relative to a brain atlas, in each of 14 patients with cranial dystonia and 8 patients with hand dystonia. The mean (left and right) |x|, y, and z coordinates of peak striatal binding for each patient were compared between groups by t test. The location of peak [(18)F]spiperone binding within the putamen differed significantly between groups (cranial dystonia zD2-like receptors are distributed differently in the putamen depending on the body part manifesting dystonia.

  18. Dopamine D2 gene expression interacts with environmental enrichment to impact lifespan and behavior

    PubMed Central

    Thanos, Panayotis K.; Hamilton, John; O'Rourke, Joseph R.; Napoli, Anthony; Febo, Marcelo; Volkow, Nora D.; Blum, Kenneth; Gold, Mark

    2016-01-01

    Aging produces cellular, molecular, and behavioral changes affecting many areas of the brain. The dopamine (DA) system is known to be vulnerable to the effects of aging, which regulate behavioral functions such as locomotor activity, body weight, and reward and cognition. In particular, age-related DA D2 receptor (D2R) changes have been of particular interest given its relationship with addiction and other rewarding behavioral properties. Male and female wild-type (Drd2 +/+), heterozygous (Drd2 +/−) and knockout (Drd2 −/−) mice were reared post-weaning in either an enriched environment (EE) or a deprived environment (DE). Over the course of their lifespan, body weight and locomotor activity was assessed. While an EE was generally found to be correlated with longer lifespan, these increases were only found in mice with normal or decreased expression of the D2 gene. Drd2 +/+ EE mice lived nearly 16% longer than their DE counterparts. Drd2 +/+ and Drd2 +/− EE mice lived 22% and 21% longer than Drd2 −/− EE mice, respectively. Moreover, both body weight and locomotor activity were moderated by environmental factors. In addition, EE mice show greater behavioral variability between genotypes compared to DE mice with respect to body weight and locomotor activity. PMID:26992232

  19. Dissociative recombination of HCl(+), H2Cl(+), DCl(+), and D2Cl(+) in a flowing afterglow.

    PubMed

    Wiens, Justin P; Miller, Thomas M; Shuman, Nicholas S; Viggiano, Albert A

    2016-12-28

    Dissociative recombination of electrons with HCl(+), H2Cl(+), DCl(+), and D2Cl(+) has been measured under thermal conditions at 300, 400, and 500 K using a flowing afterglow-Langmuir probe apparatus. Measurements for HCl(+) and DCl(+) employed the variable electron and neutral density attachment mass spectrometry (VENDAMS) method, while those for H2Cl(+) and D2Cl(+) employed both VENDAMS and the more traditional technique of monitoring electron density as a function of reaction time. At 300 K, HCl(+) and H2Cl(+) recombine with kDR = 7.7±2.1(4.5) × 10(-8) cm(3) s(-1) and 2.6 ± 0.8 × 10(-7) cm(3) s(-1), respectively, whereas D2Cl(+) is roughly half as fast as H2Cl(+) with kDR = 1.1 ± 0.3 × 10(-7) cm(3) s(-1) (2σ confidence intervals). DCl(+) recombines with a rate coefficient below the approximate detection limit of the method (≲5 × 10(-8) cm(3) s(-1)) at all temperatures. Relatively slow dissociative recombination rates have been speculated to be responsible for the large HCl(+) and H2Cl(+) abundances in interstellar clouds compared to current astrochemical models, but our results imply that the discrepancy must originate elsewhere.

  20. Frequency Comb Assisted IR Measurements of H_3^+, H_2D^+ and D_2H^+ Transitions

    NASA Astrophysics Data System (ADS)

    Jusko, Pavol; Asvany, Oskar; Schlemmer, Stephan

    2016-06-01

    We present recent measurements of the fundamental transitions of H_3^+, H_2D^+ and D_2H^+ in a 4 K 22-pole trap by action spectroscopic techniques. Either Laser Induced Inhibition of Cluster Growth (He attachment at T≈4 K), endothermic reaction of H_3^+ with O_2, or deuterium exchange has been used as measurement scheme. We used a 3 μm optical parametric oscillator coupled to a frequency comb in order to achieve accuracy generally below 1 MHz. Five transitions of H_3^+, eleven of H_2D^+ and ten of D_2H^+ were recorder in our spectral range. We compare our H_3^+ results with two previous frequency comb assisted works. Moreover, accurate determination of the frequency allows us to predict pure rotational transitions for H_2D^+ and D_2H^+ in the THz range. P. Jusko, C. Konietzko, S. Schlemmer, O. Asvany, J. Mol. Spec. 319 (2016) 55 O. Asvany, S. Brünken, L. Kluge, S. Schlemmer, Appl. Phys. B 114 (2014) 203 O. Asvany, J. Krieg, S. Schlemmer, Rev. Sci. Instr. 83 (2012) 093110 J.N. Hodges, A.J. Perry, P.A. Jenkins, B.M. Siller, B.J. McCall, J. Chem. Phys. 139 (2013) 164201 H.-C. Chen, C.-Y. Hsiao, J.-L. Peng, T. Amano, J.-T. Shy, Phys. Rev. Lett. 109 (2012) 263002

  1. Dual descriptions of spin-two massive particles in D=2+1 via master actions

    SciTech Connect

    Dalmazi, D.; Mendonca, Elias L.

    2009-02-15

    In the first part of this work we show the decoupling (up to contact terms) of redundant degrees of freedom which appear in the covariant description of spin-two massive particles in D=2+1. We make use of a master action which interpolates, without solving any constraints, between a first-, second-, and third-order (in derivatives) self-dual model. An explicit dual map between those models is derived. In our approach the absence of ghosts in the third-order self-dual model, which corresponds to a quadratic truncation of topologically massive gravity, is due to the triviality (no particle content) of the Einstein-Hilbert action in D=2+1. In the second part of the work, also in D=2+1, we prove the quantum equivalence of the gauge invariant sector of a couple of self-dual models of opposite helicities (+2 and -2) and masses m{sub +} and m{sub -} to a generalized self-dual model which contains a quadratic Einstein-Hilbert action, a Chern-Simons term of first order, and a Fierz-Pauli mass term. The use of a first-order Chern-Simons term instead of a third-order one avoids conflicts with the sign of the Einstein-Hilbert action.

  2. Dynamical properties of LiI.D2O. II. Vibrational modes and disordering effects

    NASA Astrophysics Data System (ADS)

    Migliardo, P.; Romano, G. F.; Aliotta, F.; Bartolotta, A.; di Marco, G.

    1987-12-01

    The vibrational dynamics of α-phase lithium iodide monodeuterate (LID) is investigated by Raman scattering as a function of temperature. A simple model is presented in order to explain the linkage between the D2O reorientation and the Li+ hopping motion in the superionic α form. The internal O-D stretching and D2O bending regions are analyzed, within this model, by a suitable deconvolution of the symmetric lines. Spectral contributions that might originate from two possible polarization states of the D2O molecule are discovered. Raman spectra of the melt, both in the polarized (VV) and depolarized (VH) geometries, are also presented. The experimental data reveal that the melt, in spite of stronger anharmonicity effects, exhibits the same local order which is found in the α phase. Furthermore, a measurement performed at a fixed temperature (T=-70 °C) as a function of time shows a dependence of the spectral features on time, which confirms the existence of a structural phase transition towards an orthorhombic β form, as also suggested by neutron diffraction data. The low-frequency translational region shows the characteristic broad features of a density of vibrational states both in the α phase and in the melt, thus confirming the highly cooperative nature of the dynamics of the system.

  3. Modafinil inhibits rat midbrain dopaminergic neurons through D2-like receptors.

    PubMed

    Korotkova, T M; Klyuch, B P; Ponomarenko, A A; Lin, J S; Haas, H L; Sergeeva, O A

    2007-02-01

    Modafinil is a well-tolerated medication for excessive sleepiness, attention-deficit disorder, cocaine dependence and as an adjunct to antidepressants with low propensity for abuse. We investigated the modafinil action on identified dopaminergic and GABAergic neurons in the ventral tegmental area (VTA) and substantia nigra (SN) of rat brain slices. Modafinil (20 microM) inhibited the firing of dopaminergic, but not GABAergic neurons. This inhibition was maintained in the presence of tetrodotoxin and was accompanied by hyperpolarization. Sulpiride (10 microM), a D2-receptor antagonist, but not prazosine (20 microM, an alpha1-adrenoreceptor blocker) abolished the modafinil action. Inhibition of dopamine reuptake with a low dose of nomifensine (1 microM) reduced the firing of DA neurons in a sulpiride-dependent manner and blunted the effect of modafinil. On acutely isolated neurons, modafinil evoked D2-receptor-mediated outward currents in tyrosine-hydroxylase positive cells, identified by single-cell RT-PCR, which reversed polarity near the K(+) equilibrium potential and were unchanged in the presence of nomifensine. Thus modafinil directly inhibits DA neurons through D2 receptors.

  4. Striatal dopamine D2/3 receptor availability increases after long-term bariatric surgery-induced weight loss.

    PubMed

    van der Zwaal, Esther M; de Weijer, Barbara A; van de Giessen, Elsmarieke M; Janssen, Ignace; Berends, Frits J; van de Laar, Arnold; Ackermans, Mariette T; Fliers, Eric; la Fleur, Susanne E; Booij, Jan; Serlie, Mireille J

    2016-07-01

    In several studies reduced striatal dopamine D2/3 receptor (D2/3R) availability was reported in obese subjects compared to lean controls. Whether this is a reversible phenomenon remained uncertain. We previously determined the short-term effect of Roux-en-Y gastric bypass surgery (RYGB) on striatal D2/3R availability (using [(123)I]IBZM SPECT) in 20 morbidly obese women. Striatal D2/3R availability was lower compared to controls at baseline, and remained unaltered after 6 weeks, despite significant weight loss. To determine whether long-term bariatric surgery-induced weight loss normalizes striatal D2/3R binding, we repeated striatal D2/3R binding measurements at least 2 years after RYGB in 14 subjects of the original cohort. In addition, we assessed long-term changes in body composition, eating behavior and fasting plasma levels of leptin, ghrelin, insulin and glucose. Mean body mass index declined from 46±7kg/m(2) to 32±6kg/m(2), which was accompanied by a significant increase in striatal D2/3R availability (p=0.031). Striatal D2/3R availability remained significantly reduced compared to the age-matched controls (BMI 22±2kg/m(2); p=0.01). Changes in striatal D2/3R availability did not correlate with changes in body weight/fat, insulin sensitivity, ghrelin or leptin levels. Scores on eating behavior questionnaires improved and changes in the General Food Craving Questionnaire-State showed a borderline significant correlation with changes in striatal D2/3R availability. These findings show that striatal D2/3R availability increases after long-term bariatric-surgery induced weight loss, suggesting that reduced D2/3R availability in obesity is a reversible phenomenon.

  5. New insights into the endocrine and metabolic roles of dopamine D2 receptors gained from the Drd2 mouse.

    PubMed

    Garcia-Tornadú, Isabel; Perez-Millan, Maria Ines; Recouvreux, Victoria; Ramirez, Maria Cecilia; Luque, Guillermina; Risso, Gabriela Sofia; Ornstein, Ana Maria; Cristina, Carolina; Diaz-Torga, Graciela; Becu-Villalobos, Damasia

    2010-01-01

    Dopamine D2 receptor (D2R) participation in prolactin regulation is well documented, but the role of D2Rs in the control of other hormones involved in growth, food intake and glucose metabolism has not been extensively studied. The study of D2R knockout mice (Drd2(-/-)) puts forward new insights into the role of the D2R in growth hormone (GH)-releasing hormone-GH regulation, peptides involved in food intake, glucose homeostasis, as well as in prolactinoma development. The expected phenotype of chronic hyperprolactinemia and prolactinoma development was found in the Drd2(-/-) mouse, and this model constitutes a valuable tool in the study of dopamine-resistant prolactinomas. Unexpectedly, these mice were growth retarded, and the importance of functional hypothalamic D2Rs in the neonatal period was revealed. In the Drd2(-/-) mouse there was a failure of high neonatal GH levels and therefore the expansion of pituitary somatotropes was permanently altered. These mice also had increased food intake, and a sexually dimorphic participation of the D2R in food intake regulation is suggested. The effect described is probably secondary to D2R regulation of prolactin secretion. Furthermore, the negative modulation of D2Rs on α-melanocyte-stimulating hormone release and positive action on the hypothalamic expression of orexins reveals the complex D2R regulation of food intake. Finally, pancreatic D2Rs inhibit glucose-stimulated insulin release. Lack of dopaminergic inhibition throughout development in the Drd2(-/-) mouse may exert a gradual deteriorating effect on insulin homeostasis, so that eventually glucose intolerance develops. These results highlight the complex endocrine actions of the D2Rs at different levels, hypothalamus, pituitary or pancreas, which function to improve fitness, reproductive success and survival.

  6. Inducible ablation of dopamine D2 receptors in adult mice impairs locomotion, motor skill learning and leads to severe parkinsonism.

    PubMed

    Bello, E P; Casas-Cordero, R; Galiñanes, G L; Casey, E; Belluscio, M A; Rodríguez, V; Noaín, D; Murer, M G; Rubinstein, M

    2017-04-01

    Motor execution and planning are tightly regulated by dopamine D1 and D2 receptors present in basal ganglia circuits. Although stimulation of D1 receptors is known to enhance motor function, the global effect of D2 receptor (D2R) stimulation or blockade remains highly controversial, with studies showing increasing, decreasing or no changes in motor activity. Moreover, pharmacological and genetic attempts to block or eliminate D2R have led to controversial results that questioned the importance of D2R in motor function. In this study, we generated an inducible Drd2 null-allele mouse strain that circumvented developmental compensations found in constitutive Drd2(-/-) mice and allowed us to directly evaluate the participation of D2R in spontaneous locomotor activity and motor learning. We have found that loss of D2R during adulthood causes severe motor impairments, including hypolocomotion, deficits in motor coordination, impaired learning of new motor routines and spontaneous catatonia. Moreover, severe motor impairment, resting tremor and abnormal gait and posture, phenotypes reminiscent of Parkinson's disease, were evident when the mutation was induced in aged mice. Altogether, the conditional Drd2 knockout model studied here revealed the overall fundamental contribution of D2R in motor functions and explains some of the side effects elicited by D2R blockers when used in neurological and psychiatric conditions, including schizophrenia, bipolar disorder, Tourette's syndrome, dementia, alcohol-induced delusions and obsessive-compulsive disorder.

  7. Socioeconomic status is associated with striatal dopamine D2/D3 receptors in healthy volunteers but not in cocaine abusers

    PubMed Central

    Wiers, Corinde E.; Shokri-Kojori, Ehsan; Cabrera, Elizabeth; Cunningham, Samantha; Wong, Christopher; Tomasi, Dardo; Wang, Gene-Jack; Volkow, Nora D.

    2016-01-01

    Positron emission tomography (PET) studies in animals and humans have shown that social status is associated with striatal dopamine D2/D3 receptor (D2/D3R) availability. That is, higher social hierarchy and higher scores on questionnaires assessing social status correlated positively with striatal D2/D3R availability in animals and humans respectively. Furthermore, subordinate monkeys were vulnerable to cocaine self-administration, suggesting that alternations in social hierarchy can change D2/D3R availability and vulnerability to cocaine use. Here, we investigated whether socioeconomic status (SES) measured with the Hollingshead scale is associated with striatal D2D/3R availability using [11C]raclopride PET in 38 cocaine abusers and 42 healthy controls matched for age and education. Compared to controls, cocaine abusers showed lower D2/D3R availability in the caudate, putamen and ventral striatum (all p≤.001). Despite matching groups for education, SES scores were lower in cocaine abusers than controls (p<.001). In the control group only, SES scores significantly correlated with D2/D3R in caudate (r=.35, p=.024) and putamen (r=.39, p=.011) but not in ventral striatum (p=.61); all corrected for age. The study confirms that SES is associated with striatal D2/D3R availability in healthy human volunteers. However, reductions in D2/D3R availability in cocaine abusers may be driven by factors other than SES such as chronic cocaine exposure. PMID:26828302

  8. L-DOPA disrupts adenosine A(2A)-cannabinoid CB(1)-dopamine D(2) receptor heteromer cross-talk in the striatum of hemiparkinsonian rats: biochemical and behavioral studies.

    PubMed

    Pinna, Annalisa; Bonaventura, Jordi; Farré, Daniel; Sánchez, Marta; Simola, Nicola; Mallol, Josefa; Lluís, Carme; Costa, Giulia; Baqi, Younis; Müller, Christa E; Cortés, Antoni; McCormick, Peter; Canela, Enric I; Martínez-Pinilla, Eva; Lanciego, José L; Casadó, Vicent; Armentero, Marie-Therese; Franco, Rafael

    2014-03-01

    Long-term therapy with L-3,4-dihydroxyphenylalanine (L-DOPA), still the most effective treatment in Parkinson's disease (PD), is associated with severe motor complications such as dyskinesia. Experimental and clinical data have indicated that adenosine A2A receptor antagonists can provide symptomatic improvement by potentiating L-DOPA efficacy and minimizing its side effects. It is known that the G-protein-coupled adenosine A2A, cannabinoid CB1 and dopamine D2 receptors may interact and form functional A2A-CB1-D2 receptor heteromers in co-transfected cells as well as in rat striatum. These data suggest that treatment with a combination of drugs or a single compound selectively acting on A2A-CB1-D2 heteromers may represent an alternative therapeutic treatment of PD. We investigated the expression of A2A-CB1-D2 receptor heteromers in the striatum of both naïve and hemiparkinsonian rats (HPD-rats) bearing a unilateral 6-hydroxydopamine (6-OHDA) lesion, and assessed how receptor heteromer expression and biochemical properties were affected by L-DOPA treatment. Radioligand binding data showed that A2A-CB1-D2 receptor heteromers are present in the striatum of both naïve and HPD-rats. However, behavioral results indicated that the combined administration of A2A (MSX-3 or SCH58261) and CB1 (rimonabant) receptor antagonists, in the presence of L-DOPA does not produce a response different from administration of the A2A receptor antagonist alone. These behavioral results prompted identification of heteromers in L-DOPA-treated animals. Interestingly, the radioligand binding results in samples from lesioned animals suggest that the heteromer is lost following acute or chronic treatment with L-DOPA.

  9. Bifeprunox: a partial agonist at dopamine D2 and serotonin 1A receptors, influences nicotine-seeking behaviour in response to drug-associated stimuli in rats.

    PubMed

    Di Clemente, Angelo; Franchi, Carlotta; Orrù, Alessandro; Arnt, Jorn; Cervo, Luigi

    2012-03-01

    Environmental stimuli repeatedly associated with the self-administered drugs may acquire motivational importance. Because dopamine (DA) D(2) /D(3) partial agonists and D(3) antagonists interfere with the ability of drug-associated cues to induce drug-seeking behaviour, the present study investigated whether bifeprunox, 7-[4-([1,1'biphenyl]-3-ylmethyl)-1-piperazinyl]-2(3H)-benzoxazolone mesylate), a high-affinity partial agonist of the D(2) subfamily of DA receptors and of serotonin(1A) receptors, influences reinstatement of drug-associated cue-induced nicotine-seeking behaviour. The study also explored whether bifeprunox reduced motivated behaviour by evaluating its effects on reinstatement induced by stimuli conditioned to sucrose. To verify whether bifeprunox interferes with the primary reinforcing properties of either drug or sucrose, we compared its effects on nicotine self-administration and on sucrose-reinforced behaviour. Different groups of experimentally naïve, food-restricted Wistar rats were trained to associate a discriminative stimulus with response-contingent availability of nicotine or sucrose and tested for reinstatement after extinction of nicotine or sucrose-reinforced behaviour. Bifeprunox (4-16 µg/kg, s.c.) dose-dependently attenuated the response-reinstating effects of nicotine-associated cues. Higher doses (64-250 µg/kg, s.c.) reduced spontaneous locomotor activity and suppressed operant responding induced by sucrose-associated cues and by the primary reinforcing properties of nicotine or sucrose. Provided they can be extrapolated to abstinent human addicts, these results suggest the potential therapeutic use of partial DA D(2) receptor agonist to prevent cue-controlled nicotine-seeking and relapse. The profile of action of high doses of bifeprunox remains to be examined for potential sedation or anhedonia effects.

  10. Differential Responses to Vitamin D2 and Vitamin D3 Are Associated With Variations in Free 25-Hydroxyvitamin D.

    PubMed

    Chun, Rene F; Hernandez, Ivan; Pereira, Renata; Swinkles, Leon; Huijs, Tonnie; Zhou, Rui; Liu, Nancy Q; Shieh, Albert; Guemes, Miriam; Mallya, Sanjay M; Adams, John S; Hewison, Martin

    2016-09-01

    25-Hydroxyvitamin D (25D) circulates bound primarily to serum vitamin D binding protein (DBP), with DBP showing higher binding affinity for 25D3 than 25D2. We therefore hypothesized that vitamin D2 (D2) promotes higher serum levels of unbound 25D (free 25D), with different functional responses, relative to vitamin D3 (D3). Week 3 C56BL/6 mice were placed on diets containing either D2 or D3 alone (both 1000 IU/kg). At week 8 and week 16, D2 mice had only 25D2 in circulation (26.6 ± 1.9 and 33.3 ± 4.4 ng/mL), and D3 mice had only 25D3 (28.3 ± 2.0 and 31.7 ± 2.1 ng/mL). At week 8 (44.5 ± 6.4 vs 62.4 ± 11.6 pg/mL, P < .05) and week 16 (78.4 ± 12.6 vs 95.5 ± 11.6), D2 mice had lower serum 1,25-dihydroxyvitamin D relative to D3 mice. By contrast, measured free 25D was significantly higher in D2 mice at week 8 (16.8 ± 0.65 vs 8.4 ± 0.63 pg/mL, P < .001) and week 16 (17.4 ± 0.43 vs 8.4 ± 0.44, P < .001). A two-way ANOVA of bone histomorphometry showed that week 8 D2 mice had significantly higher osteoclast surface/bone surface, eroded surface/bone surface, and mineral apposition rate compared with D3 mice. Osteoblast surface/bone surface was higher in week 8 D2 females but not week 8 D2 males. At week 16, D2 mice had significantly higher bone volume/total volume and trabecular number compared with D3 mice. Differences in bone phenotype were observed despite D2 mice reaching similar serum 25D levels and lower 1,25D levels compared with D3 mice. These data indicate that 25D2 binds less well to DBP than 25D3, with resulting higher levels of free 25D promoting differential effects on bone in mice exposed to D2 alone.

  11. Striatal Neurons Expressing D1 and D2 Receptors are Morphologically Distinct and Differently Affected by Dopamine Denervation in Mice

    PubMed Central

    Gagnon, D.; Petryszyn, S.; Sanchez, M. G.; Bories, C.; Beaulieu, J. M.; De Koninck, Y.; Parent, A.; Parent, M.

    2017-01-01

    The loss of nigrostriatal dopamine neurons in Parkinson’s disease induces a reduction in the number of dendritic spines on medium spiny neurons (MSNs) of the striatum expressing D1 or D2 dopamine receptor. Consequences on MSNs expressing both receptors (D1/D2 MSNs) are currently unknown. We looked for changes induced by dopamine denervation in the density, regional distribution and morphological features of D1/D2 MSNs, by comparing 6-OHDA-lesioned double BAC transgenic mice (Drd1a-tdTomato/Drd2-EGFP) to sham-lesioned animals. D1/D2 MSNs are uniformly distributed throughout the dorsal striatum (1.9% of MSNs). In contrast, they are heterogeneously distributed and more numerous in the ventral striatum (14.6% in the shell and 7.3% in the core). Compared to D1 and D2 MSNs, D1/D2 MSNs are endowed with a smaller cell body and a less profusely arborized dendritic tree with less dendritic spines. The dendritic spine density of D1/D2 MSNs, but also of D1 and D2 MSNs, is significantly reduced in 6-OHDA-lesioned mice. In contrast to D1 and D2 MSNs, the extent of dendritic arborization of D1/D2 MSNs appears unaltered in 6-OHDA-lesioned mice. Our data indicate that D1/D2 MSNs in the mouse striatum form a distinct neuronal population that is affected differently by dopamine deafferentation that characterizes Parkinson’s disease. PMID:28128287

  12. Association between striatal dopamine D2/D3 receptors and brain activation during visual attention: effects of sleep deprivation

    PubMed Central

    Tomasi, D; Wang, G-J; Volkow, N D

    2016-01-01

    Sleep deprivation (SD) disrupts dopamine (DA) signaling and impairs attention. However, the interpretation of these concomitant effects requires a better understanding of dopamine's role in attention processing. Here we test the hypotheses that D2/D3 receptors (D2/D3R) in dorsal and ventral striatum would distinctly regulate the activation of attention regions and that, by decreasing D2/D3, SD would disrupt these associations. We measured striatal D2/D3R using positron emission tomography with [11C]raclopride and brain activation to a visual attention (VA) task using 4-Tesla functional magnetic resonance imaging. Fourteen healthy men were studied during rested wakefulness and also during SD. Increased D2/D3R in striatum (caudate, putamen and ventral striatum) were linearly associated with higher thalamic activation. Subjects with higher D2/D3R in caudate relative to ventral striatum had higher activation in superior parietal cortex and ventral precuneus, and those with higher D2/D3R in putamen relative to ventral striatum had higher activation in anterior cingulate. SD impaired the association between striatal D2/D3R and VA-induced thalamic activation, which is essential for alertness. Findings suggest a robust DAergic modulation of cortical activation during the VA task, such that D2/D3R in dorsal striatum counterbalanced the stimulatory influence of D2/D3R in ventral striatum, which was not significantly disrupted by SD. In contrast, SD disrupted thalamic activation, which did not show counterbalanced DAergic modulation but a positive association with D2/D3R in both dorsal and ventral striatum. The counterbalanced dorsal versus ventral striatal DAergic modulation of VA activation mirrors similar findings during sensorimotor processing (Tomasi et al., 2015) suggesting a bidirectional influence in signaling between the dorsal caudate and putamen and the ventral striatum. PMID:27219347

  13. A2A-D2 receptor-receptor interaction modulates gliotransmitter release from striatal astrocyte processes.

    PubMed

    Cervetto, Chiara; Venturini, Arianna; Passalacqua, Mario; Guidolin, Diego; Genedani, Susanna; Fuxe, Kjell; Borroto-Esquela, Dasiel O; Cortelli, Pietro; Woods, Amina; Maura, Guido; Marcoli, Manuela; Agnati, Luigi F

    2017-01-01

    Evidence for striatal A2A-D2 heterodimers has led to a new perspective on molecular mechanisms involved in schizophrenia and Parkinson's disease. Despite the increasing recognition of astrocytes' participation in neuropsychiatric disease vulnerability, involvement of striatal astrocytes in A2A and D2 receptor signal transmission has never been explored. Here, we investigated the presence of D2 and A2A receptors in isolated astrocyte processes prepared from adult rat striatum by confocal imaging; the effects of receptor activation were measured on the 4-aminopyridine-evoked release of glutamate from the processes. Confocal analysis showed that A2A and D2 receptors were co-expressed on the same astrocyte processes. Evidence for A2A-D2 receptor-receptor interactions was obtained by measuring the release of the gliotransmitter glutamate: D2 receptors inhibited the glutamate release, while activation of A2A receptors, per se ineffective, abolished the effect of D2 receptor activation. The synthetic D2 peptide VLRRRRKRVN corresponding to the receptor region involved in electrostatic interaction underlying A2A-D2 heteromerization abolished the ability of the A2A receptor to antagonize the D2 receptor-mediated effect. Together, the findings are consistent with heteromerization of native striatal astrocytic A2A-D2 receptors that via allosteric receptor-receptor interactions could play a role in the control of striatal glutamatergic transmission. These new findings suggest possible new pathogenic mechanisms and/or therapeutic approaches to neuropsychiatric disorders.

  14. Saccharomyces cerevisiae Forms D-2-Hydroxyglutarate and Couples Its Degradation to D-Lactate Formation via a Cytosolic Transhydrogenase.

    PubMed

    Becker-Kettern, Julia; Paczia, Nicole; Conrotte, Jean-François; Kay, Daniel P; Guignard, Cédric; Jung, Paul P; Linster, Carole L

    2016-03-18

    The D or L form of 2-hydroxyglutarate (2HG) accumulates in certain rare neurometabolic disorders, and high D-2-hydroxyglutarate (D-2HG) levels are also found in several types of cancer. Although 2HG has been detected in Saccharomyces cerevisiae, its metabolism in yeast has remained largely unexplored. Here, we show that S. cerevisiae actively forms the D enantiomer of 2HG. Accordingly, the S. cerevisiae genome encodes two homologs of the human D-2HG dehydrogenase: Dld2, which, as its human homolog, is a mitochondrial protein, and the cytosolic protein Dld3. Intriguingly, we found that a dld3Δ knock-out strain accumulates millimolar levels of D-2HG, whereas a dld2Δ knock-out strain displayed only very moderate increases in D-2HG. Recombinant Dld2 and Dld3, both currently annotated as D-lactate dehydrogenases, efficiently oxidized D-2HG to α-ketoglutarate. Depletion of D-lactate levels in the dld3Δ, but not in the dld2Δ mutant, led to the discovery of a new type of enzymatic activity, carried by Dld3, to convert D-2HG to α-ketoglutarate, namely an FAD-dependent transhydrogenase activity using pyruvate as a hydrogen acceptor. We also provide evidence that Ser3 and Ser33, which are primarily known for oxidizing 3-phosphoglycerate in the main serine biosynthesis pathway, in addition reduce α-ketoglutarate to D-2HG using NADH and represent major intracellular sources of D-2HG in yeast. Based on our observations, we propose that D-2HG is mainly formed and degraded in the cytosol of S. cerevisiae cells in a process that couples D-2HG metabolism to the shuttling of reducing equivalents from cytosolic NADH to the mitochondrial respiratory chain via the D-lactate dehydrogenase Dld1.

  15. The effect of rock particles and D2O replacement on the flow behaviour of ice.

    PubMed

    Middleton, Ceri A; Grindrod, Peter M; Sammonds, Peter R

    2017-02-13

    Ice-rock mixtures are found in a range of natural terrestrial and planetary environments. To understand how flow processes occur in these environments, laboratory-derived properties can be extrapolated to natural conditions through flow laws. Here, deformation experiments have been carried out on polycrystalline samples of pure ice, ice-rock and D2O-ice-rock mixtures at temperatures of 263, 253 and 233 K, confining pressure of 0 and 48 MPa, rock fraction of 0-50 vol.% and strain-rates of 5 × 10(-7) to 5 × 10(-5) s(-1) Both the presence of rock particles and replacement of H2O by D2O increase bulk strength. Calculated flow law parameters for ice and H2O-ice-rock are similar to literature values at equivalent conditions, except for the value of the rock fraction exponent, here found to be 1. D2O samples are 1.8 times stronger than H2O samples, probably due to the higher mass of deuterons when compared with protons. A gradual transition between dislocation creep and grain-size-sensitive deformation at the lowest strain-rates in ice and ice-rock samples is suggested. These results demonstrate that flow laws can be found to describe ice-rock behaviour, and should be used in modelling of natural processes, but that further work is required to constrain parameters and mechanisms for the observed strength enhancement.This article is part of the themed issue 'Microdynamics of ice'.

  16. The effect of rock particles and D2O replacement on the flow behaviour of ice

    NASA Astrophysics Data System (ADS)

    Middleton, Ceri A.; Grindrod, Peter M.; Sammonds, Peter R.

    2017-02-01

    Ice-rock mixtures are found in a range of natural terrestrial and planetary environments. To understand how flow processes occur in these environments, laboratory-derived properties can be extrapolated to natural conditions through flow laws. Here, deformation experiments have been carried out on polycrystalline samples of pure ice, ice-rock and D2O-ice-rock mixtures at temperatures of 263, 253 and 233 K, confining pressure of 0 and 48 MPa, rock fraction of 0-50 vol.% and strain-rates of 5 × 10-7 to 5 × 10-5 s-1. Both the presence of rock particles and replacement of H2O by D2O increase bulk strength. Calculated flow law parameters for ice and H2O-ice-rock are similar to literature values at equivalent conditions, except for the value of the rock fraction exponent, here found to be 1. D2O samples are 1.8 times stronger than H2O samples, probably due to the higher mass of deuterons when compared with protons. A gradual transition between dislocation creep and grain-size-sensitive deformation at the lowest strain-rates in ice and ice-rock samples is suggested. These results demonstrate that flow laws can be found to describe ice-rock behaviour, and should be used in modelling of natural processes, but that further work is required to constrain parameters and mechanisms for the observed strength enhancement. This article is part of the themed issue 'Microdynamics of ice'.

  17. Dopamine D2 receptor status assessed by IBZM SPECT - A sensitive indicator for cerebral hypoxia

    SciTech Connect

    Tatsch, K.; Schwarz, J.; Welz, A.

    1995-05-01

    The striatum is highly sensitive to tissue hypoxia. Thus, it may be suggested that cerebral hypoxia could affect the integrity of the striatal receptor system. Purpose of the current SPECT investigations with IBZM was to evaluate whether hypoxic conditions cause detectable changes in the D2 receptor status. 25 controls and 30 pts with history of cerebral hypoxia (resuscitation after cardiac arrest: n=19, CABG surgery under cardiopulmonary bypass: n=11) were investigated with SPECT 2h p.i. of 185 MBq I-123 IBZM. For semiquant, evaluation transverse slices corrected for attenuation were used to calculate striatal to frontal cortex (S/FC) ratios. In 13/19 pts with cerebral hypoxia due to cardiac arrest IBZM binding was severely reduced after successful resuscitation. 7 died, 5 were in a vegetative state, 1 remained severely disabled. In 6/19 S/FC ratios were normal/mildly reduced, 2 of them had a good outcome, 4 were moderatley disabled. In pts with CABG IBZM binding was preoperatively normal. After hypoxia due to cardiac surgery striatal S/FC ratios decreased slightly, persisting on this level even 6 months after surgery. Neuropsychological/psychiatric testing showed only minor or transient changes in this group of patients. The striatal D2 receptor status seems to be a sensitive indicator for cerebral hypoxia. After hypoxia due to cardiac arrest IBZM results well correlate (in contrast to morphological or SEP findings) with the clinical outcome and thus may serve as early predictor of the individual prognosis. The moderate decline in IBZM binding following CABG surgery suggests mild cerebral hypoxia despite of protective hypothermia. Sensitively indicating cerebral hypoxia changes in the D2 receptor status assessed by IBZM SPECT may serve as a valuable diagnostic tool for testing neuroprotective drugs or modified surgical techniques.

  18. Time-Dependence of Risperidone and Asenapine Sensitization and Associated D2 receptor Mechanism

    PubMed Central

    Gao, Jun; Li, Ming

    2013-01-01

    When an antipsychotic drug is given repeatedly and intermittently, there is often a long-term increase in its behavioral efficacy, termed antipsychotic sensitization. With the passage of time, the magnitude of antipsychotic sensitization may increase or decrease depending on the principle of Time-Dependent Sensitization (TDS) or memory decay, respectively. In the present study, we examined the time-dependent feature and possible dopamine D2 receptor mechanism of sensitization induced by the antipsychotics risperidone and asenapine in the conditioned avoidance response test. Well-trained male adult Sprague-Dawley rats were first repeatedly treated with risperidone (1.0 mg/kg) or asenapine (0.2 mg/kg) and tested for avoidance response daily for 5 consecutive days. Eight, 18 or 38 days after the 5th drug treatment, all rats were retested drug-free to assess the residual impact of prior risperidone or asenapine treatment. Drug-pretreated rats had significantly lower avoidance than vehicle-pretreated ones on this test, and the group differences increased with the passage of time. In the subsequent drug challenge test at 10, 20 or 40 days after the 5th drug treatment, all rats were injected with a low dose of risperidone (0.3 mg/kg) or asenapine (0.1 mg/kg). Drug-pretreated rats again made significantly less avoidances than controls, confirming the drug-induced sensitization effect. Finally, in the quinpirole (a D2/3 receptor agonist, 1.0 mg/kg, sc)-induced hyperlocomotion test, risperidone-pretreated rats exhibited a significantly higher level of motor activity than the vehicle-pretreated ones. These findings suggest that risperidone and asenapine sensitization is long-lasting, follows the TDS principle, and is likely mediated by D2 receptor supersensitivity. PMID:24103641

  19. Gradient-based 3D-2D registration of cerebral angiograms

    NASA Astrophysics Data System (ADS)

    Mitrović, Uroš; Markelj, Primož; Likar, Boštjan; Miloševič, Zoran; Pernuš, Franjo

    2011-03-01

    Endovascular treatment of cerebral aneurysms and arteriovenous malformations (AVM) involves navigation of a catheter through the femoral artery and vascular system into the brain and into the aneurysm or AVM. Intra-interventional navigation utilizes digital subtraction angiography (DSA) to visualize vascular structures and X-ray fluoroscopy to localize the endovascular components. Due to the two-dimensional (2D) nature of the intra-interventional images, navigation through a complex three-dimensional (3D) structure is a demanding task. Registration of pre-interventional MRA, CTA, or 3D-DSA images and intra-interventional 2D DSA images can greatly enhance visualization and navigation. As a consequence of better navigation in 3D, the amount of required contrast medium and absorbed dose could be significantly reduced. In the past, development and evaluation of 3D-2D registration methods received considerable attention. Several validation image databases and evaluation criteria were created and made publicly available in the past. However, applications of 3D-2D registration methods to cerebral angiograms and their validation are rather scarce. In this paper, the 3D-2D robust gradient reconstruction-based (RGRB) registration algorithm is applied to CTA and DSA images and analyzed. For the evaluation purposes five image datasets, each comprised of a 3D CTA and several 2D DSA-like digitally reconstructed radiographs (DRRs) generated from the CTA, with accurate gold standard registrations were created. A total of 4000 registrations on these five datasets resulted in mean mTRE values between 0.07 and 0.59 mm, capture ranges between 6 and 11 mm and success rates between 61 and 88% using a failure threshold of 2 mm.

  20. Energy Efficient IoT Data Collection in Smart Cities Exploiting D2D Communications

    PubMed Central

    Orsino, Antonino; Araniti, Giuseppe; Militano, Leonardo; Alonso-Zarate, Jesus; Molinaro, Antonella; Iera, Antonio

    2016-01-01

    Fifth Generation (5G) wireless systems are expected to connect an avalanche of “smart” objects disseminated from the largest “Smart City” to the smallest “Smart Home”. In this vision, Long Term Evolution-Advanced (LTE-A) is deemed to play a fundamental role in the Internet of Things (IoT) arena providing a large coherent infrastructure and a wide wireless connectivity to the devices. However, since LTE-A was originally designed to support high data rates and large data size, novel solutions are required to enable an efficient use of radio resources to convey small data packets typically exchanged by IoT applications in “smart” environments. On the other hand, the typically high energy consumption required by cellular communications is a serious obstacle to large scale IoT deployments under cellular connectivity as in the case of Smart City scenarios. Network-assisted Device-to-Device (D2D) communications are considered as a viable solution to reduce the energy consumption for the devices. The particular approach presented in this paper consists in appointing one of the IoT smart devices as a collector of all data from a cluster of objects using D2D links, thus acting as an aggregator toward the eNodeB. By smartly adapting the Modulation and Coding Scheme (MCS) on the communication links, we will show it is possible to maximize the radio resource utilization as a function of the total amount of data to be sent. A further benefit that we will highlight is the possibility to reduce the transmission power when a more robust MCS is adopted. A comprehensive performance evaluation in a wide set of scenarios will testify the achievable gains in terms of energy efficiency and resource utilization in the envisaged D2D-based IoT data collection. PMID:27338385

  1. Energy Efficient IoT Data Collection in Smart Cities Exploiting D2D Communications.

    PubMed

    Orsino, Antonino; Araniti, Giuseppe; Militano, Leonardo; Alonso-Zarate, Jesus; Molinaro, Antonella; Iera, Antonio

    2016-06-08

    Fifth Generation (5G) wireless systems are expected to connect an avalanche of "smart" objects disseminated from the largest "Smart City" to the smallest "Smart Home". In this vision, Long Term Evolution-Advanced (LTE-A) is deemed to play a fundamental role in the Internet of Things (IoT) arena providing a large coherent infrastructure and a wide wireless connectivity to the devices. However, since LTE-A was originally designed to support high data rates and large data size, novel solutions are required to enable an efficient use of radio resources to convey small data packets typically exchanged by IoT applications in "smart" environments. On the other hand, the typically high energy consumption required by cellular communications is a serious obstacle to large scale IoT deployments under cellular connectivity as in the case of Smart City scenarios. Network-assisted Device-to-Device (D2D) communications are considered as a viable solution to reduce the energy consumption for the devices. The particular approach presented in this paper consists in appointing one of the IoT smart devices as a collector of all data from a cluster of objects using D2D links, thus acting as an aggregator toward the eNodeB. By smartly adapting the Modulation and Coding Scheme (MCS) on the communication links, we will show it is possible to maximize the radio resource utilization as a function of the total amount of data to be sent. A further benefit that we will highlight is the possibility to reduce the transmission power when a more robust MCS is adopted. A comprehensive performance evaluation in a wide set of scenarios will testify the achievable gains in terms of energy efficiency and resource utilization in the envisaged D2D-based IoT data collection.

  2. Differential Modulation of Reinforcement Learning by D2 Dopamine and NMDA Glutamate Receptor Antagonism

    PubMed Central

    Klein, Tilmann A.; Ullsperger, Markus

    2014-01-01

    The firing pattern of midbrain dopamine (DA) neurons is well known to reflect reward prediction errors (PEs), the difference between obtained and expected rewards. The PE is thought to be a crucial signal for instrumental learning, and interference with DA transmission impairs learning. Phasic increases of DA neuron firing during positive PEs are driven by activation of NMDA receptors, whereas phasic suppression of firing during negative PEs is likely mediated by inputs from the lateral habenula. We aimed to determine the contribution of DA D2-class and NMDA receptors to appetitively and aversively motivated reinforcement learning. Healthy human volunteers were scanned with functional magnetic resonance imaging while they performed an instrumental learning task under the influence of either the DA D2 receptor antagonist amisulpride (400 mg), the NMDA receptor antagonist memantine (20 mg), or placebo. Participants quickly learned to select (“approach”) rewarding and to reject (“avoid”) punishing options. Amisulpride impaired both approach and avoidance learning, while memantine mildly attenuated approach learning but had no effect on avoidance learning. These behavioral effects of the antagonists were paralleled by their modulation of striatal PEs. Amisulpride reduced both appetitive and aversive PEs, while memantine diminished appetitive, but not aversive PEs. These data suggest that striatal D2-class receptors contribute to both approach and avoidance learning by detecting both the phasic DA increases and decreases during appetitive and aversive PEs. NMDA receptors on the contrary appear to be required only for approach learning because phasic DA increases during positive PEs are NMDA dependent, whereas phasic decreases during negative PEs are not. PMID:25253860

  3. 26 CFR 1.927(d)-2T - Temporary regulations; definitions and special rules relating to Foreign Sales Corporation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... involving direct sales to F, each of X and Y is a related supplier of F. (b) Definition of related party... rules relating to Foreign Sales Corporation. 1.927(d)-2T Section 1.927(d)-2T Internal Revenue INTERNAL... relating to Foreign Sales Corporation. (a) Definition of related supplier. For purposes of sections...

  4. Loss of Feedback Inhibition via D2 Autoreceptors Enhances Acquisition of Cocaine Taking and Reactivity to Drug-Paired Cues

    PubMed Central

    Holroyd, Kathryn B; Adrover, Martin F; Fuino, Robert L; Bock, Roland; Kaplan, Alanna R; Gremel, Christina M; Rubinstein, Marcelo; Alvarez, Veronica A

    2015-01-01

    A prominent aspect of drug addiction is the ability of drug-associated cues to elicit craving and facilitate relapse. Understanding the factors that regulate cue reactivity will be vital for improving treatment of addictive disorders. Low availability of dopamine (DA) D2 receptors (D2Rs) in the striatum is associated with high cocaine intake and compulsive use. However, the role of D2Rs of nonstriatal origin in cocaine seeking and taking behavior and cue reactivity is less understood and possibly underestimated. D2Rs expressed by midbrain DA neurons function as autoreceptors, exerting inhibitory feedback on DA synthesis and release. Here, we show that selective loss of D2 autoreceptors impairs the feedback inhibition of DA release and amplifies the effect of cocaine on DA transmission in the nucleus accumbens (NAc) in vitro. Mice lacking D2 autoreceptors acquire a cued-operant self-administration task for cocaine faster than littermate control mice but acquire similarly for a natural reward. Furthermore, although mice lacking D2 autoreceptors were able to extinguish self-administration behavior in the absence of cocaine and paired cues, they exhibited perseverative responding when cocaine-paired cues were present. This enhanced cue reactivity was selective for cocaine and was not seen during extinction of sucrose self-administration. We conclude that low levels of D2 autoreceptors enhance the salience of cocaine-paired cues and can contribute to the vulnerability for cocaine use and relapse. PMID:25547712

  5. Leptin Increases Striatal Dopamine D2 Receptor Binding in Leptin-Deficient Obese (ob/ob) Mice

    SciTech Connect

    Pfaffly, J.; Michaelides, M.; Wang, G-J.; Pessin, J.E.; Volkow, N.D.; Thanos, P.K.

    2010-06-01

    Peripheral and central leptin administration have been shown to mediate central dopamine (DA) signaling. Leptin-receptor deficient rodents show decreased DA D2 receptor (D2R) binding in striatum and unique DA profiles compared to controls. Leptin-deficient mice show increased DA activity in reward-related brain regions. The objective of this study was to examine whether basal D2R-binding differences contribute to the phenotypic behaviors of leptin-deficient ob/ob mice, and whether D2R binding is altered in response to peripheral leptin treatment in these mice. Leptin decreased body weight, food intake, and plasma insulin concentration in ob/ob mice but not in wild-type mice. Basal striatal D2R binding (measured with autoradiography [{sup 3}H] spiperone) did not differ between ob/ob and wild-type mice but the response to leptin did. In wild-type mice, leptin decreased striatal D2R binding, whereas, in ob/ob mice, leptin increased D2R binding. Our findings provide further evidence that leptin modulates D2R expression in striatum and that these effects are genotype/phenotype dependent.

  6. Interaction with Dopamine D2 Receptor Enhances Expression of Transient Receptor Potential Channel 1 at the Cell Surface

    PubMed Central

    Hannan, Meredith A.; Kabbani, Nadine; Paspalas, Constantinos D.; Levenson, Robert

    2008-01-01

    Receptor signaling is mediated by direct protein interaction with various types of cytoskeletal, adapter, effector, and additional receptor molecules. In brain tissue and in cultured neurons, activation of dopamine D2 receptors (D2Rs) has been found to impact cellular calcium signaling. Using a yeast two-hybrid approach, we have uncovered a direct physical interaction between the D2R and the transient receptor potential channel (TRPC) subtypes 1, 4 and 5. The TRPC/D2R interaction was further validated by GST-pulldown assays and coimmunoprecipitation from mammalian brain. Ultrastructural analysis of TRPC1 and D2R expression indicates colocalization of the two proteins within the cell body and dendrites of cortical neurons. In cultured cells, expression of D2Rs was found to increase expression of TRPC1 at the cell surface by 50%. These findings shed new light on the constituents of the D2R signalplex, and support the involvement of D2Rs in cellular calcium signaling pathways via a novel link to TRPC channels. PMID:18261457

  7. 75 FR 28080 - Program for Allocation of Regulatory Responsibilities Pursuant to Rule 17d-2; Order Approving and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-19

    ... COMMISSION Program for Allocation of Regulatory Responsibilities Pursuant to Rule 17d-2; Order Approving and Declaring Effective a Plan for the Allocation of Regulatory Responsibilities Between the Financial Industry... allocation of regulatory responsibilities, dated March 31, 2010 (``17d- 2 Plan'' or the ``Plan''). The...

  8. 75 FR 28078 - Program for Allocation of Regulatory Responsibilities Pursuant to Rule 17d-2; Order Approving and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-19

    ... COMMISSION Program for Allocation of Regulatory Responsibilities Pursuant to Rule 17d-2; Order Approving and Declaring Effective a Plan for the Allocation of Regulatory Responsibilities Between the Financial Industry... allocation of regulatory responsibilities, dated March 31, 2010 (``17d- 2 Plan'' or the ``Plan''). The...

  9. Cp2TiCl/D2O/Mn, a formidable reagent for the deuteration of organic compounds

    PubMed Central

    Rodríguez-García, Ignacio

    2016-01-01

    Summary Cp2TiCl/D2O/Mn is an efficient combination, sustainable and cheap reagent that mediates the D-atom transfer from D2O to different functional groups and can contribute to the synthesis of new deuterated organic compounds under friendly experimental conditions and with great economic advantages. PMID:27559410

  10. Fully Differential Cross Sections for Photo-Double-Ionization of D2_

    NASA Astrophysics Data System (ADS)

    Weber, Th.; Czasch, A.; Jagutzki, O.; Müller, A.; Mergel, V.; Kheifets, A.; Feagin, J.; Rotenberg, E.; Meigs, G.; Prior, M. H.; Daveau, S.; Landers, A. L.; Cocke, C. L.; Osipov, T.; Schmidt-Böcking, H.; Dörner, R.

    2004-04-01

    We report the first kinematically complete study of the four-body fragmentation of the D2 molecule following absorption of a single photon. For equal energy sharing of the two electrons and a photon energy of 75.5eV, we observed the relaxation of one of the selection rules valid for He photo-double-ionization and a strong dependence of the electron angular distribution on the orientation of the molecular axis. This effect is reproduced by a model in which a pair of photoionization amplitudes is introduced for the light polarization parallel and perpendicular to the molecular axis.

  11. Surgical care quality and oncologic outcome after D2 gastrectomy for gastric cancer

    PubMed Central

    Mrena, Johanna; Mattila, Anne; Böhm, Jan; Jantunen, Ismo; Kellokumpu, Ilmo

    2015-01-01

    AIM: To examine the quality of surgical care and long-term oncologic outcome after D2 gastrectomy for gastric cancer. METHODS: From 1999 to 2008, a total of 109 consecutive patients underwent D2 gastrectomy without routine pancreaticosplenectomy in a multimodal setting at our institution. Oncologic outcomes together with clinical and histopathologic data were analyzed in relation to the type of surgery performed. Staging was carried out according to the Union for International Cancer Control criteria of 2002. Patients were followed-up for five years at the outpatient clinic. The primary measure of outcome was long-term survival with the quality of surgery as a secondary outcome measure. Clinical data were retrospectively collected from the patient records, and causes of death were obtained from national registries. RESULTS: A total of 109 patients (58 men) with a mean age of 67.4 ± 11.2 years underwent total gastrectomy or gastric resection with D2 lymph node dissection. The tumor stage distribution was as follows: stage I, (27/109) 24.8%; stage II, (31/109) 28.4%; stage III, (41/109) 37.6%; and stage IV, (10/109) 9.2%. Forty patients (36.7%) received chemotherapy or chemoradiotherapy. The five-year overall survival rate for all 109 patients was 45.0%, and was 47.1% for the 104 patients treated with curative R0 resection. The five-year disease-specific survival rates were 53.0% and 55.8%, respectively. In a multivariate analysis, body mass index and tumor stage were independent prognostic factors for overall survival (both P < 0.01), whereas body mass index, tumor stage, tumor site, Lauren classification, and lymph node invasion were prognostic factors for cancer-specific survival (all P < 0.05). Postoperative 30-d mortality was 1.8% and 30-d, surgical (including three anastomotic leaks, two of which were treated conservatively), and general morbidities were 26.6%, 12.8%, and 14.7%, respectively. CONCLUSION: D2 dissection is a safe surgical option for gastric

  12. STS-55 Columbia, OV-102, crew poses for onboard portrait in SL-D2 module

    NASA Technical Reports Server (NTRS)

    1993-01-01

    STS-55 Columbia, Orbiter Vehicle (OV) 102, crewmembers pose for their traditional onboard (inflight) portrait in the Spacelab Deutsche 2 (SL-D2) science module. Front (left to right) are Pilot Terence T. Henricks, Commander Steven R. Nagel, German Payload Specialist 1 Ulrich Walter, and Mission Specialist 2 (MS2) Charles J. Precourt. In the rear (left to right) are MS3 Bernard A. Harris, Jr, German Payload Specialist 2 Hans Schlegel, and MS1 and Payload Commander (PLC) Jerry L. Ross. Walter and Schlegel represent the German Aerospace Research Establishment (DLR).

  13. Cryogenic implementation of charging diamond anvil cells with H2 and D2.

    PubMed

    Chi, Zhenhua; Nguyen, Huyen; Matsuoka, Takahiro; Kagayama, Tomoko; Hirao, Naohisa; Ohishi, Yasuo; Shimizu, Katsuya

    2011-10-01

    A cryogenic loading system for introducing H(2) and D(2) into the diamond anvil cell has been designed and constructed. The integration of pressure loading mechanism, ruby fluorescence spectrometer, and microscope camera allows for in situ tuning and calibrating the pressure. The performance of the system has been demonstrated by successful synthesis of hydride and deuteride of transition metal and rare earth metal. Our cryogenic methodology features facile start-over of loading and in situ electrical resistance measurement of as-synthesized sample.

  14. Studies of Elementary Processes and Coupling Involved in the D2/F2 Chemical Laser.

    DTIC Science & Technology

    1986-12-01

    number," -he performance of a H chemicll 1lser is a function of the nascent enerc.y disosl praetrs 2ort F + H D2) and H (0) + F2 chemical reactions...solution for approximately 18 hours followed by several washings with distilled water . The tube was then filled with a 10 M HNO 3 solution for...approximately 18 hours, washed several times with distilled water and dried. Detection System Infrared radiation from the reaction products is focused by a

  15. STS-55 SL-D2 crew reviews preflight CEIT procedures in KSC conference room

    NASA Technical Reports Server (NTRS)

    1993-01-01

    STS-55 Spacelab Deutsche 2 (SL-D2) crewmembers, seated at a conference table, discuss Crew Equipment Interface Test (CEIT) procedures in a briefing room at the Kennedy Space Center (KSC). From left are Mission Specialist 1 (MS1) and Payload Commander (PLC) Jerry L. Ross, German Payload Specialist 1 Ulrich Walter, Pilot Terence T. Henricks, Commander Steven R. Nagel, MS3 Bernard J. Harris, Jr, German Payload Specialist 2 Hans Schlegel, and MS2 Charles J. Precourt. Seated in the foreground are KSC technicians and payload integration officers. Walter and Schlegel are representatives from DLR. View provided by KSC with alternate KSC number KSC-93PC-212.

  16. μCF Experiments in D2 and HD Gases Final Results

    NASA Astrophysics Data System (ADS)

    Voropaev, N. I.; Balin, D. V.; Breunlich, W. H.; Case, T.; Crowe, K. M.; Faifman, M. P.; Gartner, B.; Hartmann, F. J.; Kammel, P.; Lauss, B.; Maev, E. M.; Markushin, V. E.; Petitjean, C.; Petrov, G. E.; Schapkin, G. N.; Semenchuk, G. G.; Vorobyov, A. A.; Zmeskal, J.

    2001-12-01

    During 1994 1996, a series of μCF experiments were performed at PSI by the PSI-PNPI-IMEP-LBNL-TUM collaboration. These experiments aimed at high-precision studies of the d μ d fusion in D2 and HD gases in a wide temperature range. The Gatchina ionization time projection chamber has been used to detect the dd-fusion reaction products. The main parameters of the d μ d fusion have been measured with high absolute precision. In this report, we present the results of the final analysis of the experimental data. The obtained results are compared with the calculations based on a recent μCF-theory.

  17. Dopamine D2 receptor relies upon PPM/PP2C protein phosphatases to dephosphorylate huntingtin protein.

    PubMed

    Marion, Sébastien; Urs, Nikhil M; Peterson, Sean M; Sotnikova, Tatyana D; Beaulieu, Jean-Martin; Gainetdinov, Raul R; Caron, Marc G

    2014-04-25

    Striatal dopamine D2 receptor (D2R) relies upon G protein- and β-arrestin-dependent signaling pathways to convey its action on motor control and behavior. Considering that D2R activation inhibits Akt in the striatum and that huntingtin physiological functions are affected by Akt phosphorylation, we sought to investigate whether D2R-mediated signaling could regulate huntingtin phosphorylation. We demonstrate that D2R activation decreases huntingtin phosphorylation on its Akt site. This dephosphorylation event depends upon the Gαi-dependent engagement of specific members of the protein phosphatase metallo-dependent (PPM/PP2C) family and is independent of β-arrestin 2. These observations identify the PPM/PP2C family as a mediator of G protein-coupled receptor signaling and thereby suggest a novel mechanism of dopaminergic signaling.

  18. RGS2 modulates the activity and internalization of dopamine D2 receptors in neuroblastoma N2A cells.

    PubMed

    Luessen, Deborah J; Hinshaw, Tyler P; Sun, Haiguo; Howlett, Allyn C; Marrs, Glen; McCool, Brian A; Chen, Rong

    2016-11-01

    Dysregulated expression and function of dopamine D2 receptors (D2Rs) are implicated in drug addiction, Parkinson's disease and schizophrenia. In the current study, we examined whether D2Rs are modulated by regulator of G protein signaling 2 (RGS2), a member of the RGS family that regulates G protein signaling via acceleration of GTPase activity. Using neuroblastoma 2a (N2A) cells, we found that RGS2 was immunoprecipitated by aluminum fluoride-activated Gαi2 proteins. RGS2 siRNA knockdown enhanced membrane [(35)S] GTPγS binding to activated Gαi/o proteins, augmented inhibition of cAMP accumulation and increased ERK phosphorylation in the presence of a D2/D3R agonist quinpirole when compared to scrambled siRNA treatment. These data suggest that RGS2 is a negative modulator of D2R-mediated Gαi/o signaling. Moreover, RGS2 knockdown slightly increased constitutive D2R internalization and markedly abolished quinpirole-induced D2R internalization assessed by immunocytochemistry. RGS2 knockdown did not compromise agonist-induced β-arrestin membrane recruitment; however, it prevents β-arrestin dissociation from the membrane after prolonged quinpirole treatment during which time β-arrestin moved away from the membrane in control cells. Additionally, confocal microscopy analysis of β-arrestin post-endocytic fate revealed that quinpirole treatment caused β-arrestin to translocate to the early and the recycling endosome in a time-dependent manner in control cells whereas translocation of β-arrestin to these endosomes did not occur in RGS2 knockdown cells. The impaired β-arrestin translocation likely contributed to the abolishment of quinpirole-stimulated D2R internalization in RGS2 knockdown cells. Thus, RGS2 is integral for β-arrestin-mediated D2R internalization. The current study revealed a novel regulation of D2R signaling and internalization by RGS2 proteins.

  19. Transcriptional activation of the SH2D2A gene is dependent on a cyclic adenosine 5'-monophosphate-responsive element in the proximal SH2D2A promoter.

    PubMed

    Dai, Ke-Zheng; Johansen, Finn-Eirik; Kolltveit, Kristin Melkevik; Aasheim, Hans-Christian; Dembic, Zlatko; Vartdal, Frode; Spurkland, Anne

    2004-05-15

    The SH2D2A gene, encoding the T cell-specific adapter protein (TSAd), is rapidly induced in activated T cells. In this study we investigate the regulation of the SH2D2A gene in Jurkat T cells and in primary T cells. Reporter gene assays demonstrated that the proximal 1-kb SH2D2A promoter was constitutively active in Jurkat TAg T cells and, to a lesser extent, in K562 myeloid cells, Reh B cells, and 293T fibroblast cells. The minimal SH2D2A promoter was located between position -236 and -93 bp from the first coding ATG, and transcriptional activity in primary T cells depended on a cAMP response element (CRE) centered around position -117. Nuclear extracts from Jurkat TAg cells and activated primary T cells contained binding activity to this CRE, as observed in an EMSA. Consistent with this observation, we found that a cAMP analog was a very potent inducer of SH2D2A mRNA expression in primary T cells as measured by real-time RT-PCR. Furthermore, activation of SH2D2A expression by CD3 stimulation required cAMP-dependent protein kinase activity. Thus, transcriptional regulation of the SH2D2A gene in activated T cells is critically dependent on a CRE in the proximal promoter region.

  20. Plant Enzymes but Not Agrobacterium VirD2 Mediate T-DNA Ligation In Vitro

    PubMed Central

    Ziemienowicz, Alicja; Tinland, Bruno; Bryant, John; Gloeckler, Veronique; Hohn, Barbara

    2000-01-01

    Agrobacterium tumefaciens, a gram-negative soil bacterium, transfers DNA to many plant species. In the plant cell, the transferred DNA (T-DNA) is integrated into the genome. An in vitro ligation-integration assay has been designed to investigate the mechanism of T-DNA ligation and the factors involved in this process. The VirD2 protein, which is produced in Agrobacterium and is covalently attached to T-DNA, did not, under our assay conditions, ligate T-DNA to a model target sequence in vitro. We tested whether plant extracts could ligate T-DNA to target oligonucleotides in our test system. The in vitro ligation-integration reaction did indeed take place in the presence of plant extracts. This reaction was inhibited by dTTP, indicating involvement of a plant DNA ligase. We found that prokaryotic DNA ligases could substitute for plant extracts in this reaction. Ligation of the VirD2-bound oligonucleotide to the target sequence mediated by T4 DNA ligase was less efficient than ligation of a free oligonucleotide to the target. T-DNA ligation mediated by a plant enzyme(s) or T4 DNA ligase requires ATP. PMID:10938108

  1. Dosimetry on the Spacelab missions IML1 and IML2, and D2 and on MIR.

    PubMed

    Reitz, G; Beaujean, R; Heilmann, C; Kopp, J; Leicher, M; Strauch, K

    1996-11-01

    Detector packages consisting of plastic nuclear track detectors, nuclear emulsions, and thermoluminescence detectors were exposed inside BIORACK during the Spacelab missions IML1 and IML2, in different sections of the MIR space station, and inside the Spacelab module at rack front panels or stowage lockers and in the Spacelab tunnel during D2. In addition, during D2, each Payload Specialist (PS) has worn three permanent detector packages; one at the neck; one at the waist; and one at the ankle. Total dose measurements, particle fluence rate and LET spectra, number of nuclear disintegrations and neutron dose from this exposure are given in this report. The results are compared to theoretical calculations and to previous missions results. The dose equivalent (total radiation exposure) received by the PSs were calculated from the measurements and range from 190 to 770 microSv d-1. Finally, a cursory investigation of results from a particle telescope from two silicon detectors, first used in the last BIORACK mission on STS76, is reported.

  2. Electrolysis byproduct D2O provides a third way to mitigate CO2

    SciTech Connect

    Schenewerk, William Ernest

    2009-09-01

    Rapid atomic power deployment may be possible without using fast breeder reactors or making undue demands on uranium resource. Using by-product D2O and thorium-U233 in CANDU and RBMK piles may circumvent need for either fast breeder reactors or seawater uranium. Atmospheric CO2 is presently increasing 2.25%/year in proportion to 2.25%/year exponential fossil fuel consumption increase. Roughly 1/3 anthropologic CO2 is removed by various CO2 sinks. CO2 removal is modelled as being proportional to 45-year-earlier CO2 amount above 280 ppm-C Water electrolysis produces roughly 0.1 kg-D20/kWe-y. Material balance assumes each electrolysis stage increases D2O bottoms concentration times 3. Except for first two electrolysis stages, all water from hydrogen consumption is returned to electrolysis. The unique characteristic of this process is the ability to economically burn all deuterium-enriched H2 in vehicles. Condensate from vehicles returns to appropriate electrolysis stage. Fuel cell condensate originally from reformed natural gas may augment second-sage feed. Atomic power expansion is 5%/year, giving 55000 GWe by 2100. World primary energy increases 2.25%/y, exceeding 4000 EJ/y by 2100. CO2 maximum is roughly 600 ppm-C around year 2085. CO2 declines back below 300 ppm-C by 2145 if the 45-year-delay seawater sink remains effective.

  3. Telemetry distribution and processing for the second German Spacelab Mission D-2

    NASA Technical Reports Server (NTRS)

    Rabenau, E.; Kruse, W.

    1994-01-01

    For the second German Spacelab Mission D-2 all activities related to operating, monitoring and controlling the experiments on board the Spacelab were conducted from the German Space Operations Control Center (GSOC) operated by the Deutsche Forschungsanstalt fur Luft- und Raumfahrt (DLR) in Oberpfaffenhofen, Germany. The operational requirements imposed new concepts on the transfer of data between Germany and the NASA centers and the processing of data at the GSOC itself. Highlights were the upgrade of the Spacelab Data Processing Facility (SLDPF) to real time data processing, the introduction of packet telemetry and the development of the high-rate data handling front end, data processing and display systems at GSOC. For the first time, a robot on board the Spacelab was to be controlled from the ground in a closed loop environment. A dedicated forward channel was implemented to transfer the robot manipulation commands originating from the robotics experiment ground station to the Spacelab via the Orbiter's text and graphics system interface. The capability to perform telescience from an external user center was implemented. All interfaces proved successful during the course of the D-2 mission and are described in detail in this paper.

  4. Niobium boride layers deposition on the surface AISI D2 steel by a duplex treatment

    SciTech Connect

    Kon, O.; Pazarlioglu, S.

    2015-03-30

    In this paper, we investigated the possibility of deposition of niobium boride layers on the surface of AISI D2 steel by a duplex treatment. At the first step of duplex treatment, boronizing was performed on AISI D2 steel samples at 1000{sup o}C for 2h and then pre-boronized samples niobized at 850°C, 900°C and 950°C using thermo-reactive deposition method for 1–4 h. The presence of the niobium boride layers such as NbB, NbB{sub 2} and Nb{sub 3}B{sub 4} and also iron boride phases such as FeB, Fe{sub 2}B were examined by X-ray diffraction analysis. Scanning electron microscope (SEM) and micro-hardness measurements were realized. Experimental studies showed that the depth of the coating layers increased with increasing temperature and times and also ranged from 0.42 µm to 2.43 µm, depending on treatment time and temperature. The hardness of the niobium boride layer was 2620±180 HV{sub 0.005}.

  5. Far infrared spectrum of Methanol-D2 in the lowest torsional state (e0)

    NASA Astrophysics Data System (ADS)

    Mukhopadhyay, Indra

    2016-03-01

    The infrared (IR) and far infrared (FIR) absorption spectra have been measured for the Methanol-D1 and D2 species in the wave number range of 20-1200 cm-1 at the Justus Liebig Universität in Giessen, Germany using a Brüker Fourier Transform spectrometer at a resolution of 0.002 cm-1. The spectra looked very complicated but analyses were possible for the lower lying states. At higher wave number regions spectra of few vibrational fundamental modes were visible. In this communication, the details of the assignments and analyses of the lowest lying internal rotational state (e0) for Methanol-D2 are reported. A catalog of about 900 assigned spectral lines has been prepared and is made available from the author to conserve space. As application of this work, it was possible to assign some optically pumped FIR laser lines to quantum states. The results should be useful for "radio astronomers" and in the field of optically pumped FIR and Sub-millimeter Wave (SMMW) lasers which are used in Tokamaks for plasma diagnostics and as local oscillators in radio detection from space.

  6. 16Oxygen irradiation enhances cued fear memory in B6D2F1 mice

    NASA Astrophysics Data System (ADS)

    Raber, Jacob; Marzulla, Tessa; Kronenberg, Amy; Turker, Mitchell S.

    2015-11-01

    The space radiation environment includes energetic charged particles that may impact cognitive performance. We assessed the effects of 16O ion irradiation on cognitive performance of C57BL/6J × DBA/2J F1 (B6D2F1) mice at OHSU (Portland, OR) one month following irradiation at Brookhaven National Laboratory (BNL, Upton, NY). Hippocampus-dependent contextual fear memory and hippocampus-independent cued fear memory of B6D2F1 mice were tested. 16O ion exposure enhanced cued fear memory. This effect showed a bell-shaped dose response curve. Cued fear memory was significantly stronger in mice irradiated with 16O ions at a dose of 0.4 or 0.8 Gy than in sham-irradiated mice or following irradiation at 1.6 Gy. In contrast to cued fear memory, contextual fear memory was not affected following 16O ion irradiation at the doses used in this study. These data indicate that the amygdala might be particularly susceptible to effects of 16O ion exposure.

  7. The vibrational Stokes shift of water (HOD in D2O)

    NASA Astrophysics Data System (ADS)

    Wang, Zhaohui; Pang, Yoonsoo; Dlott, Dana D.

    2004-05-01

    The vibrational Stokes shift of the OH stretching transition νOH of water is the shift between the ground-state absorption and the excited-state (v=1) emission. A recent measurement on HOD in D2O solvent [S. Woutersen and H. J. Bakker, Phys. Rev. Lett. 83, 2077 (1999)] of a 70 cm-1 redshift, and a subsequent calculation of a 57 cm-1 redshift using equilibrium molecular dynamics simulations [C. P. Lawrence and J. L. Skinner, J. Chem. Phys. 117, 8847 (2002)] were in good agreement. We now report extensive measurements of the vibrational Stokes shift in HOD/D2O using an ultrafast IR pump, Raman probe method. The vibrational Stokes shift is seen to depend on the pump pulse frequency and on time delay; by varying these parameters it can be made to range from 112 to -32 cm-1 (negative values indicate a blueshift in the excited state). The equilibrium vibrational Stokes shift is actually a negative rather than a positive quantity. Possible reasons for the disagreement between experiment and theory are briefly discussed.

  8. Infrared Spectroscopy of the H2/HD/D2-O2 Van Der Waals Complexes

    NASA Astrophysics Data System (ADS)

    Raston, Paul; Bunn, Hayley

    2016-06-01

    Hydrogen is the most abundant element in the universe and oxygen is the third, so understanding the interaction between the two in their different forms is important to understanding astrochemical processes. The interaction between H2 and O2 has been explored in low energy scattering experiments and by far infrared synchrotron spectroscopy of the van der Waals complex. The far infrared spectra suggest a parallel stacked average structure with seven bound rotationally excited states. Here, we present the far infrared spectrum of HD/D2-O2 and the mid infrared spectrum of H2-O2 at 80 K, recorded at the infrared beamline facility of the Australian Synchrotron. We observed 'sharp' peaks in the mid infrared region, corresponding to the end over end rotation of H2-O2, that are comparatively noisier than analogous peaks in the far infrared where the synchrotron light is brightest. The larger reduced mass of HD and D2 compared to H2 is expected to result in more rotational bound states and narrower bands. The latest results in our ongoing efforts to explore this system will be presented. Y. Kalugina, et al., Phys. Chem. Chem. Phys. 14, 16458 (2012) S. Chefdeville et al. Science 341, 1094 (2013) H. Bunn et al. ApJ 799, 65 (2015)

  9. 3D/2D registration and segmentation of scoliotic vertebrae using statistical models.

    PubMed

    Benameur, Said; Mignotte, Max; Parent, Stefan; Labelle, Hubert; Skalli, Wafa; de Guise, Jacques

    2003-01-01

    We propose a new 3D/2D registration method for vertebrae of the scoliotic spine, using two conventional radiographic views (postero-anterior and lateral), and a priori global knowledge of the geometric structure of each vertebra. This geometric knowledge is efficiently captured by a statistical deformable template integrating a set of admissible deformations, expressed by the first modes of variation in Karhunen-Loeve expansion, of the pathological deformations observed on a representative scoliotic vertebra population. The proposed registration method consists of fitting the projections of this deformable template with the preliminary segmented contours of the corresponding vertebra on the two radiographic views. The 3D/2D registration problem is stated as the minimization of a cost function for each vertebra and solved with a gradient descent technique. Registration of the spine is then done vertebra by vertebra. The proposed method efficiently provides accurate 3D reconstruction of each scoliotic vertebra and, consequently, it also provides accurate knowledge of the 3D structure of the whole scoliotic spine. This registration method has been successfully tested on several biplanar radiographic images and validated on 57 scoliotic vertebrae. The validation results reported in this paper demonstrate that the proposed statistical scheme performs better than other conventional 3D reconstruction methods.

  10. Cabergoline, dopamine D2 receptor agonist, prevents neuronal cell death under oxidative stress via reducing excitotoxicity.

    PubMed

    Odaka, Haruki; Numakawa, Tadahiro; Adachi, Naoki; Ooshima, Yoshiko; Nakajima, Shingo; Katanuma, Yusuke; Inoue, Takafumi; Kunugi, Hiroshi

    2014-01-01

    Several lines of evidence demonstrate that oxidative stress is involved in the pathogenesis of neurodegenerative diseases, including Parkinson's disease. Potent antioxidants may therefore be effective in the treatment of such diseases. Cabergoline, a dopamine D2 receptor agonist and antiparkinson drug, has been studied using several cell types including mesencephalic neurons, and is recognized as a potent radical scavenger. Here, we examined whether cabergoline exerts neuroprotective effects against oxidative stress through a receptor-mediated mechanism in cultured cortical neurons. We found that neuronal death induced by H₂O₂ exposure was inhibited by pretreatment with cabergoline, while this protective effect was eliminated in the presence of a dopamine D2 receptor inhibitor, spiperone. Activation of ERK1/2 by H₂O₂ was suppressed by cabergoline, and an ERK signaling pathway inhibitor, U0126, similarly protected cortical neurons from cell death. This suggested the ERK signaling pathway has a critical role in cabergoline-mediated neuroprotection. Furthermore, increased extracellular levels of glutamate induced by H₂O₂, which might contribute to ERK activation, were reduced by cabergoline, while inhibitors for NMDA receptor or L-type Ca²⁺ channel demonstrated a survival effect against H₂O₂. Interestingly, we found that cabergoline increased expression levels of glutamate transporters such as EAAC1. Taken together, these results suggest that cabergoline has a protective effect on cortical neurons via a receptor-mediated mechanism including repression of ERK1/2 activation and extracellular glutamate accumulation induced by H₂O₂.

  11. Dopamine D2 Modulation of Sign and Goal Tracking in Rats.

    PubMed

    Lopez, Juan Carlos; Karlsson, Rose-Marie; O'Donnell, Patricio

    2015-08-01

    In Pavlovian conditioning, sign- and goal-tracking behaviors represent different approaches towards the conditioned stimulus. These behavioral patterns have been associated with predictive or incentive properties of the conditioned stimulus, with a crucial involvement of the mesolimbic dopamine system. As it is possible that sign tracking behavior is more sensitive to dopamine modulation, we evaluated the dopamine-dependence of sign- and goal-tracking behavior. We assessed responses to both a D2 agonist and an antagonist, and tested performance in a behavioral paradigm known to activate dopamine projections and in an animal model that affects mesolimbic and mesocortical function. Sign trackers displayed a greater sensitivity to a D2 agonist and smaller prepulse inhibition of the acoustic startle response than goal trackers, suggesting a reduced inhibitory ability. In addition, a neonatal ventral hippocampal lesion resulted in the loss of incentive salience of cues in sign trackers. Overall, these data indicate that sign-tracking behavior is more heavily controlled by dopamine than goal tracking.

  12. Dopamine D2 Modulation of Sign and Goal Tracking in Rats

    PubMed Central

    Lopez, Juan Carlos; Karlsson, Rose-Marie; O'Donnell, Patricio

    2015-01-01

    In Pavlovian conditioning, sign- and goal-tracking behaviors represent different approaches towards the conditioned stimulus. These behavioral patterns have been associated with predictive or incentive properties of the conditioned stimulus, with a crucial involvement of the mesolimbic dopamine system. As it is possible that sign tracking behavior is more sensitive to dopamine modulation, we evaluated the dopamine-dependence of sign- and goal-tracking behavior. We assessed responses to both a D2 agonist and an antagonist, and tested performance in a behavioral paradigm known to activate dopamine projections and in an animal model that affects mesolimbic and mesocortical function. Sign trackers displayed a greater sensitivity to a D2 agonist and smaller prepulse inhibition of the acoustic startle response than goal trackers, suggesting a reduced inhibitory ability. In addition, a neonatal ventral hippocampal lesion resulted in the loss of incentive salience of cues in sign trackers. Overall, these data indicate that sign-tracking behavior is more heavily controlled by dopamine than goal tracking. PMID:25759299

  13. Comparison of three high affinity SPECT radiotracers for the dopamine D2 receptor.

    PubMed

    al-Tikriti, M S; Baldwin, R M; Zea-Ponce, Y; Sybirska, E; Zoghbi, S S; Laruelle, M; Malison, R T; Kung, H F; Kessler, R M; Charney, D S

    1994-02-01

    The regional brain distribution and pharmacological specificity of three high affinity tracers for the dopamine (DA) D2 receptor: [123I]IBF, [123I]epidepride, and [123I]2'-ISP were assessed by SPECT imaging of non-human primates. The ratios of striatal-to-occipital activities at the time of peak striatal uptake were 2.2, 6.3 and 1.7, respectively. From the peak striatal activities, washout rates were 33, 4 and 16%/h for [123I]IBF, [123I]epidepride and [123I]2'-ISP, respectively. The reversibility of the striatal uptake of all three agents was demonstrated by the rapid displacement induced by the dopamine D2 selective antipsychotic agent raclopride, which increased washout rates to 96, 58 and 43%/h. The administration of d-amphetamine, which induces release of dopamine, had no noticeable effect on [123I]epidepride but increased the washout rate of [123I]IBF. These results suggest that, among these three agents, [123I]epidepride is the superior tracer for in vivo displacement studies because of its slow washout and high target-to-background ratios. However, for tracer kinetic modeling, [123I]IBF may be the superior agent because of its early time of peak uptake and its higher target-to-background ratios than [123I]2'-ISP.

  14. Neurovascular coupling to D2/D3 dopamine receptor occupancy using simultaneous PET/functional MRI

    PubMed Central

    Sander, Christin Y.; Hooker, Jacob M.; Catana, Ciprian; Normandin, Marc D.; Alpert, Nathaniel M.; Knudsen, Gitte M.; Vanduffel, Wim; Rosen, Bruce R.; Mandeville, Joseph B.

    2013-01-01

    This study employed simultaneous neuroimaging with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) to demonstrate the relationship between changes in receptor occupancy measured by PET and changes in brain activity inferred by fMRI. By administering the D2/D3 dopamine receptor antagonist [11C]raclopride at varying specific activities to anesthetized nonhuman primates, we mapped associations between changes in receptor occupancy and hemodynamics [cerebral blood volume (CBV)] in the domains of space, time, and dose. Mass doses of raclopride above tracer levels caused increases in CBV and reductions in binding potential that were localized to the dopamine-rich striatum. Moreover, similar temporal profiles were observed for specific binding estimates and changes in CBV. Injection of graded raclopride mass doses revealed a monotonic coupling between neurovascular responses and receptor occupancies. The distinct CBV magnitudes between putamen and caudate at matched occupancies approximately matched literature differences in basal dopamine levels, suggesting that the relative fMRI measurements reflect basal D2/D3 dopamine receptor occupancy. These results can provide a basis for models that relate dopaminergic occupancies to hemodynamic changes in the basal ganglia. Overall, these data demonstrate the utility of simultaneous PET/fMRI for investigations of neurovascular coupling that correlate neurochemistry with hemodynamic changes in vivo for any receptor system with an available PET tracer. PMID:23723346

  15. Neurovascular coupling to D2/D3 dopamine receptor occupancy using simultaneous PET/functional MRI.

    PubMed

    Sander, Christin Y; Hooker, Jacob M; Catana, Ciprian; Normandin, Marc D; Alpert, Nathaniel M; Knudsen, Gitte M; Vanduffel, Wim; Rosen, Bruce R; Mandeville, Joseph B

    2013-07-02

    This study employed simultaneous neuroimaging with positron emission tomography (PET) and functional magnetic resonance imaging (fMRI) to demonstrate the relationship between changes in receptor occupancy measured by PET and changes in brain activity inferred by fMRI. By administering the D2/D3 dopamine receptor antagonist [(11)C]raclopride at varying specific activities to anesthetized nonhuman primates, we mapped associations between changes in receptor occupancy and hemodynamics [cerebral blood volume (CBV)] in the domains of space, time, and dose. Mass doses of raclopride above tracer levels caused increases in CBV and reductions in binding potential that were localized to the dopamine-rich striatum. Moreover, similar temporal profiles were observed for specific binding estimates and changes in CBV. Injection of graded raclopride mass doses revealed a monotonic coupling between neurovascular responses and receptor occupancies. The distinct CBV magnitudes between putamen and caudate at matched occupancies approximately matched literature differences in basal dopamine levels, suggesting that the relative fMRI measurements reflect basal D2/D3 dopamine receptor occupancy. These results can provide a basis for models that relate dopaminergic occupancies to hemodynamic changes in the basal ganglia. Overall, these data demonstrate the utility of simultaneous PET/fMRI for investigations of neurovascular coupling that correlate neurochemistry with hemodynamic changes in vivo for any receptor system with an available PET tracer.

  16. Inhibition of creatine kinase activity from rat cerebral cortex by D-2-hydroxyglutaric acid in vitro.

    PubMed

    da Silva, Cleide G; Bueno, Ana Rúbia F; Schuck, Patrícia F; Leipnitz, Guilhian; Ribeiro, César A J; Rosa, Rafael B; Dutra Filho, Carlos S; Wyse, Angela T S; Wannmacher, Clóvis M D; Wajner, Moacir

    2004-01-01

    D-2-Hydroxyglutaric acid (DGA) is the biochemical hallmark of patients affected by the neurometabolic disorder known as D-2-hydroxyglutaric aciduria (DHGA). Although this disease is predominantly characterized by severe neurological findings, the underlying mechanisms of brain injury are virtually unknown. In the present study, we investigated the effect of DGA on total, cytosolic, and mitochondrial creatine kinase (CK) activities from cerebral cortex of 30-day-old Wistar rats. Total CK activity (tCK) was measured in whole cell homogenates, whereas cytosolic and mitochondrial activities were measured in the cytosolic and mitochondrial preparations from cerebral cortex. We verified that CK activities were significantly inhibited by DGA (11-34% inhibition) at concentrations as low as 0.25 mM, being the mitochondrial fraction the most affected activity. Kinetic studies revealed that the inhibitory effect of DGA was non-competitive in relation to phosphocreatine. We also observed that this inhibition was fully prevented by pre-incubation of the homogenates with reduced glutathione, suggesting that the inhibitory effect of DGA on tCK activity is possibly mediated by oxidation of essential thiol groups of the enzyme. Considering the importance of CK activity for brain metabolism homeostasis, our results suggest that inhibition of this enzyme by increased levels of DGA may be related to the neurodegeneration of patients affected by DHGA.

  17. Synthesis and evaluation of geometric analogs of 1α,25-dihydroxyvitamin D2 as potential therapeutics.

    PubMed

    Bolla, Narasimha Rao; Corcoran, Aoife; Yasuda, Kaori; Chodyński, Michał; Krajewski, Krzysztof; Cmoch, Piotr; Marcinkowska, Ewa; Brown, Geoffrey; Sakaki, Toshiyuki; Kutner, Andrzej

    2016-11-01

    An improved convergent strategy was developed for the synthesis of the previously obtained side-chain extended and rigidified analogs of 1α,25-dihydroxyvitamin D2, PRI-1906 and PRI-1907. New (24Z) geometric isomers of the analogs, PRI-1916 and PRI-1917, were also obtained and identified. These side-chain isomers were separable by flash chromatography, as C-25 alcohols, from the synthetic precursors of PRI-1906 and PRI-1907, respectively. The structures of new analogs were determined by advanced techniques of (1)H and (13)C NMR, including COSY, HSQC and HMBC sequences. Binding affinities of the geometric analogs PRI-1906 and PRI-1916 and their respective C-26, C-27 homologs PRI-1907 and PRI-1917 for the full-length human vitamin D receptor were determined by a fluorescence polarization competition assay. The binding affinity of (24Z) methyl analog PRI-1906 was much higher than that of (24E) analog PRI-1906, while the affinity of (24Z) ethyl analog PRI-1917 was lower than that of the respective PRI-1907. Investigation of the metabolism of these compounds by human CYP24A1 revealed they are much more resistant to CYP24A1 than 1α,25-dihydroxyvitamin D2, indicating they could have longer-term biological effects on target tissues.

  18. ATM induces MacroD2 nuclear export upon DNA damage

    PubMed Central

    Golia, Barbara; Moeller, Giuliana Katharina; Jankevicius, Gytis; Schmidt, Andreas; Hegele, Anna; Preißer, Julia; Tran, Mai Ly; Imhof, Axel; Timinszky, Gyula

    2017-01-01

    ADP-ribosylation is a dynamic post-translation modification that regulates the early phase of various DNA repair pathways by recruiting repair factors to chromatin. ADP-ribosylation levels are defined by the activities of specific transferases and hydrolases. However, except for the transferase PARP1/ARDT1 little is known about regulation of these enzymes. We found that MacroD2, a mono-ADP-ribosylhydrolase, is exported from the nucleus upon DNA damage, and that this nuclear export is induced by ATM activity. We show that the export is dependent on the phosphorylation of two SQ/TQ motifs, suggesting a novel direct interaction between ATM and ADP-ribosylation. Lastly, we show that MacroD2 nuclear export temporally restricts its recruitment to DNA lesions, which may decrease the net ADP-ribosylhydrolase activity at the site of DNA damage. Together, our results identify a novel feedback regulation between two crucial DNA damage-induced signaling pathways: ADP-ribosylation and ATM activation. PMID:28069995

  19. Effects of Rotational State Excitations on the Dissociative Adsorption Dynamics of D2/Cu(111)

    NASA Astrophysics Data System (ADS)

    Diño, Wilson; Kasai, Hideaki; Okiji, Ayao

    1995-07-01

    Recent time-of-flight experiments show a non-monotonous dependence of the dissociative adsorption/sticking* probability of D2(H2)/Cu(111) on the initial rotational state. There is an observed decrease in the sticking probability with a slight increase in the initial rotational state quantum number j. As j is increased further, the sticking probability eventually increases. We show that, to account for this interesting behaviour, there are two opposing factors working for and against the adsorption process: STEERING EFFECT and ENERGY TRANSFER EFFECT. The first is dueto a dynamical reorientation of the molecule, and the latter is due to the coupling of therotational motion to the translational motion along the reaction path. To illustrate these two effects, we performed quantum mechanical model calculations using a variation of the coupled-channel method, a physically realistic model potential based on available potential energy (hyper-) surface plots for D2(H2)/Cu for two different orientations-parallel and perpendicular to the surface, and the concept of a reaction path.

  20. Synthesis and characterization of iodobenzamide analogues: Potential D-2 dopamine receptor imaging agents

    SciTech Connect

    Murphy, R.A.; Kung, H.F.; Kung, M.P.; Billings, J. )

    1990-01-01

    (S)-N-((1-Ethyl-2-pyrrolidinyl)methyl)-2-hydroxy-3-iodo-6- methoxybenzamide (({sup 123}I)IBZM) is a central nervous system (CNS) D-2 dopamine receptor imaging agent. In order to investigate the versatility of this parent structure in specific dopamine receptor localization and the potential for developing new dopamine receptor imaging agents, a series of new iodinated benzamides with fused ring systems, naphthalene (INAP) and benzofuran (IBF), was synthesized and radiolabeled, and the in vivo and in vitro biological properties were characterized. The best analogue of IBZM is IBF (21). The specific binding of ({sup 125}I)IBF (21) with rat striatal tissue preparation was found to be saturable and displayed a Kd of 0.106 {plus minus} 0.015 nM. Competition data of various receptor ligands for ({sup 125}I)IBF (21) binding show the following rank order of potency: spiperone greater than IBF (21) greater than IBZM greater than (+)-butaclamol greater than ({plus minus})-ADTN,6,7 greater than ketanserin greater than SCH-23390 much greater than propranolol. The in vivo biodistribution results confirm that ({sup 125}I)IBF (21) concentrated in the striatal area after iv injection into rats. The study demonstrates that ({sup 123}I)IBF (21) is a potential agent for imaging CNS D-2 dopamine receptors.

  1. Long-range magnetic order in the Heisenberg pyrochlore antiferromagnets G d2G e2O7 and G d2P t2O7 synthesized under high pressure

    NASA Astrophysics Data System (ADS)

    Li, X.; Cai, Y. Q.; Cui, Q.; Lin, C. J.; Dun, Z. L.; Matsubayashi, K.; Uwatoko, Y.; Sato, Y.; Kawae, T.; Lv, S. J.; Jin, C. Q.; Zhou, J.-S.; Goodenough, J. B.; Zhou, H. D.; Cheng, J.-G.

    2016-12-01

    G d2S n2O7 and G d2T i2O7 have been regarded as good experimental realizations of the classical Heisenberg pyrochlore antiferromagnet with dipolar interaction. The former was found to adopt the Palmer-Chalker state via a single, first-order transition at TN≈1 K , while the latter enters a distinct, partially ordered state through two successive transitions at TN 1≈1 K and TN 2= 0.75 K . To shed more light on their distinct magnetic ground states, we have synthesized two more gadolinium-based pyrochlore oxides, G d2G e2O7 and G d2P t2O7 , under high-pressure conditions and performed detailed characterizations via x-ray powder diffraction, dc and ac magnetic susceptibility, and specific heat measurements down to 100 mK. We found that both compounds enter a long-range antiferromagnetically ordered state through a single, first-order transition at TN= 1.4 K for G d2G e2O7 and TN= 1.56 K for G d2P t2O7 , with the specific heat anomaly similar to that of G d2S n2O7 rather than G d2T i2O7 . Interestingly, the low-temperature magnetic specific heat values of both G d2G e2O7 and G d2P t2O7 were found to follow nicely the T3 dependence as expected for a three-dimensional antiferromagnet with gapless spin-wave excitations. We have rationalized the enhancement of TN in terms of the reduced Gd-Gd distances for the chemically pressurized G d2G e2O7 and the addition of extra superexchange pathways through the empty Pt -eg orbitals for G d2P t2O7 . Our current study has expanded the family of gadolinium-based pyrochlores and permits us to achieve a better understanding of their distinct magnetic properties in a more comprehensive perspective.

  2. Genetic dissection of leukemia-associated IDH1 and IDH2 mutants and D-2-hydroxyglutarate in Drosophila

    PubMed Central

    Reitman, Zachary J.; Sinenko, Sergey A.; Spana, Eric P.

    2015-01-01

    Gain-of-function mutations in nicotinamide adenine dinucleotide phosphate–dependent isocitrate dehydrogenase (IDH)1 and IDH2 frequently arise in human leukemias and other cancers and produce high levels of D-2-hydroxyglutarate (D-2HG). We expressed the R195H mutant of Drosophila Idh (CG7176), which is equivalent to the human cancer-associated IDH1-R132H mutant, in fly tissues using the UAS-Gal4 binary expression system. Idh-R195H caused a >25-fold elevation of D-2HG when expressed ubiquitously in flies. Expression of mutant Idh in larval blood cells (hemocytes) resulted in higher numbers of circulating blood cells. Mutant Idh expression in fly neurons resulted in neurologic and wing-expansion defects, and these phenotypes were rescued by genetic modulation of superoxide dismutase 2, p53, and apoptotic caspase cascade mediators. Idh-R163Q, which is homologous to the common leukemia-associated IDH2-R140Q mutant, resulted in moderately elevated D-2HG and milder phenotypes. We identified the fly homolog of D-2-hydroxyglutaric acid dehydrogenase (CG3835), which metabolizes D-2HG, and showed that coexpression of this enzyme with mutant Idh abolishes mutant Idh-associated phenotypes. These results provide a flexible model system to interrogate a cancer-related genetic and metabolic pathway and offer insights into the impact of IDH mutation and D-2HG on metazoan tissues. PMID:25398939

  3. The ins and outs of GluD2--why and how Purkinje cells use the special glutamate receptor.

    PubMed

    Yuzaki, Michisuke

    2012-06-01

    The δ2 glutamate receptor (GluD2) is predominantly expressed in cerebellar Purkinje cells and plays crucial roles in cerebellar functions. Indeed, the number of synapses between parallel fibers (PFs) and Purkinje cells is specifically and severely reduced in GluD2-null cerebellum. In addition, long-term depression (LTD) at PF-Purkinje cell synapses is impaired in these mice. Nevertheless, the mechanism by which GluD2 regulate these two functions-morphological and functional synaptic plasticity at PF synapses-has remained unclear. Recently, we found that Cbln1, a glycoprotein released from granule cells, was bound to the N-terminal domain of GluD2 and regulated formation and maintenance of PF-Purkinje cell synapses. Furthermore, we found that D: -Ser released from Bergmann glia bound the ligand-binding domain of GluD2 and mediated LTD in a manner dependent on the C-terminus. These findings indicate how GluD2 is activated and regulates functions at PF-Purkinje cell synapses. A hypothesis about why GluD2 is employed by PF synapses is also discussed.

  4. Dopamine D2 receptor suppresses gastric cancer cell invasion and migration via inhibition of EGFR/AKT/MMP-13 pathway.

    PubMed

    Huang, Hongli; Wu, Kaiming; Ma, Jun; Du, Yanlei; Cao, Chuangyu; Nie, Yuqiang

    2016-10-01

    Dopamine (DA), an important neurotransmitter, has been reported to play a negative role in tumor progression. DA acts its role via dopamine receptors (DRs), which can be divided into five receptor subtypes (D1R-D5R). Among these receptor subtypes, D2R has been found to inhibit IGF-I-induced gastric cancer cell growth. However, the functions of D2R in gastric cancer cell invasion remain elusive. Here, we found that D2R expression was decreased in gastric cancer cells. DA treatment dose-dependently inhibited EGF-mediated gastric cancer cell invasion and migration via D2R. Furthermore, D2R decreased EGF-mediated MMP-13 production, and attenuated EGFR and AKT activation. Together with the results that EGF promoted gastric cancer cell invasion and migration via EGFR/AKT pathway, these data indicate that DA treatment, acting via D2R, suppresses gastric cancer cell invasion and migration via inhibition of EGFR/AKT/MMP-13 pathway. Thus, our findings suggest that use of D2R agonist may have a potential therapeutic effect on gastric cancer.

  5. Oncometabolite D-2-Hydroxyglurate Directly Induces Epithelial-Mesenchymal Transition and is Associated with Distant Metastasis in Colorectal Cancer

    PubMed Central

    Colvin, Hugh; Nishida, Naohiro; Konno, Masamitsu; Haraguchi, Naotsugu; Takahashi, Hidekazu; Nishimura, Junichi; Hata, Taishi; Kawamoto, Koichi; Asai, Ayumu; Tsunekuni, Kenta; Koseki, Jun; Mizushima, Tsunekazu; Satoh, Taroh; Doki, Yuichiro; Mori, Masaki; Ishii, Hideshi

    2016-01-01

    Deranged metabolism is a hallmark of cancer, playing a significant role in driving the disease process. One such example is the induction of carcinogenesis by the oncometabolite D-2 hydroxyglutarate (D-2HG), which is produced by the mutated enzyme isocitrate dehydrogenase (IDH) occurring in subsets of leukaemias and brain tumours. The oncogenic property of D-2HG appears to stem from its ability to interfere with the activities of α-ketoglutarate-dependent dioxygenases, including the Jumonji family histone demethylases. Here, we find in colorectal cancer cells that even in the absence of IDH mutation, the levels of D-2HG and its enantiomer L-2HG were elevated through glutamine anaplerosis. D-2HG, but not L-2HG, increased the trimethylation of histone H3 lysine 4 of the promoter region of ZEB1, a master regulator of epithelial-mesenchymal transition (EMT), and increased the expression of the ZEB1 gene to directly induce EMT in colorectal cancer cells. EMT promotes the ability of cancer cells to invade the local tissue and enter into the bloodstream, leading to distant organ metastasis. D-2HG levels were elevated in colorectal cancer specimens, particularly in those associated with distant metastasis, supporting the observations in vitro and implicating the contribution of D-2HG in metastasis, the major cause of death in this disease. PMID:27824159

  6. Pituitary and brain D2 receptor density measured in vitro and in vivo in EEDQ treated male rats

    SciTech Connect

    Ekman, A.; Eriksson, E. )

    1991-01-01

    The effect of the alkylating compound N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) on dopamine D2 receptor density in rat pituitary and brain was measured using in vitro and in vivo radioligand binding techniques. In the in vitro radioligand binding experiments EEDQ was found to reduce the density (B{sub max}) of ({sup 3}H)-spiperone binding sites in the striatum by 86% while in the pituitary the corresponding decrease was only 37%. The affinity (K{sub D}) of the remaining striatal and pituitary D2 receptors was not different in EEDQ treated animals as compared to controls. When D2 receptor density was measured in vivo the effect of EEDQ was less pronounced. Thus, in rats given EEDQ the specific binding of either of the two D2 ligands ({sup 3}H)-raclopride or ({sup 3}H)-spiperone in striatum and in the limbic forebrain was reduced by 45-62%; moreover, no significant decrease in pituitary D2 receptor density was observed. The data are discussed in relation to the finding that the same dose of EEDQ that failed to influence pituitary D2 receptor density as measured in vivo effectively antagonizes the prolactin decreasing effect of the partial D2 agonist (-)-3-(3-hydroxyphenyl)-N-n-propyl-piperidine ((-)-3-PPP).

  7. Cow hair allergen (Bos d 2) content in house dust: correlation with sensitization in farmers with cow hair asthma.

    PubMed

    Hinze, S; Bergmann, K C; Løwenstein, H; Hansen, G N

    1997-03-01

    Farmers (N = 45) suffering from occupational cow hair asthma were visited at home to evaluate the concentration of cow hair major allergen Bos d 2 in the house dust and to correlate these results with measures of avoidance, degree of sensitization, clinical symptoms, and lung function. Bos d 2 was determined by rocket immunoelectrophoresis. In dust of tiles and linoleum Bos d 2 was difficult to detect, whereas dust samples of carpets often contained high concentrations of the allergen (50-520 micrograms/g fine dust). Bos d 2 levels were significantly higher when barn and living quarters were in the same building. Concentrations of cow hair-specific IgE were correlated with concentrations of Bos d 2 in house dust samples. A concentration of 20-29 micrograms Bos d 2 per gram of house dust could be established as threshold value for relevant IgE sensitization. Avoiding the barn is not a sufficient avoidance measure for cow hair asthmatics if the partner continues cattle farming. Cessation of cattle farming and avoiding the former barn results in a marked reduction in Bos d 2 concentration in living quarters, a decreased degree of sensitization, and a reduced symptom score. Farmers with cow hair asthma should avoid cattle and thoroughly clean all carpets in the living quarters to avoid continuous cow allergen exposure.

  8. UV-dependent production of 25-hydroxyvitamin D2 in the recombinant yeast cells expressing human CYP2R1.

    PubMed

    Yasuda, Kaori; Endo, Mariko; Ikushiro, Shinichi; Kamakura, Masaki; Ohta, Miho; Sakaki, Toshiyuki

    2013-05-03

    CYP2R1 is known to be a physiologically important vitamin D 25-hydroxylase. We have successfully expressed human CYP2R1 in Saccharomyces cerevisiae to reveal its enzymatic properties. In this study, we examined production of 25-hydroxylated vitamin D using whole recombinant yeast cells that expressed CYP2R1. When vitamin D3 or vitamin D2 was added to the cell suspension of CYP2R1-expressing yeast cells in a buffer containing glucose and β-cyclodextrin, the vitamins were converted into their 25-hydroxylated products. Next, we irradiated the cell suspension with UVB and incubated at 37 °C. Surprisingly, the 25-hydroxy vitamin D2 was produced without additional vitamin D2. Endogenous ergosterol was likely converted into vitamin D2 by UV irradiation and thermal isomerization, and then the resulting vitamin D2 was converted to 25-hydroxyvitamin D2 by CYP2R1. This novel method for producing 25-hydroxyvitamin D2 without a substrate could be useful for practical purposes.

  9. Impact of sulfur and vitamin C on the allergenicity of Mal d 2 from apple (Malus domestica).

    PubMed

    Marzban, Gorji; Kinaciyan, Tamar; Maghuly, Fatemeh; Brunner, Richard; Gruber, Clemens; Hahn, Rainer; Jensen-Jarolim, Erika; Laimer, Margit

    2014-07-30

    Mal d 2 is a minor allergen from apple which shows a high conformational stability due to its eight conserved disulfide bridges. Chemical reduction of disulfide bridges and linearization of Mal d 2 lead to enhanced IgE reactivity in vitro and indicate a higher potential for allergenicity. Since food preservatives such as sulfur and vitamin C are reducing and denaturing agents, their influence on Mal d 2 allergenicity was verified by simulated food processing conditions. The immunoreactivity of purified Mal d 2 was investigated after different treatments in vitro and in vivo using IgG/IgE Western blotting, mediator-releasing cell assay, and skin prick and oral smear tests. The conformational changes of Mal d 2 upon addition of 1% and 5% vitamin C were also monitored by attenuated total reflectance Fourier transform infrared spectroscopy. The results show no positive skin and oral smear test reactivity to native, heated, or vitamin C-treated purified Mal d 2. Furthermore, the results confirm that sulfur in combination with heat treatment can influence the structural integrity and thus the allergenicity of Mal d 2, while vitamin C is too weak as a reducing agent to change allergenicity.

  10. Comparison of the Binding and Functional Properties of Two Structurally Different D2 Dopamine Receptor Subtype Selective Compounds

    PubMed Central

    2012-01-01

    We previously reported on the synthesis of substituted phenyl-4-hydroxy-1-piperidyl indole analogues with nanomolar affinity at D2 dopamine receptors, ranging from 10- to 100-fold selective for D2 compared to the D3 dopamine receptor subtype. More recently, we evaluated a panel of aripiprazole analogues, identifying several analogues that also exhibit D2 vs D3 dopamine receptor binding selectivity. These studies further characterize the intrinsic efficacy of the compound with the greatest binding selectivity from each chemical class, 1-((5-methoxy-1H-indol-3-yl)methyl)-4-(4-(methylthio)phenyl)piperidin-4-ol (SV 293) and 7-(4-(4-(2-methoxyphenyl)piperazin-1-yl)butoxy)-3,4-dihydroquinolin-2(1H)-one (SV-III-130s), using an adenylyl cyclase inhibition assay, a G-protein-coupled inward-rectifying potassium (GIRK) channel activation assay, and a cell based phospho-MAPK (pERK1/2) assay. SV 293 was found to be a neutral antagonist at D2 dopamine receptors using all three assays. SV-III-130s is a partial agonist using an adenylyl cyclase inhibition assay but an antagonist in the GIRK and phospho ERK1/2 assays. To define the molecular basis for the binding selectivity, the affinity of these two compounds was evaluated using (a) wild type human D2 and D3 receptors and (b) a panel of chimeric D2/D3 dopamine receptors. Computer-assisted modeling techniques were used to dock these compounds to the human D2 and D3 dopamine receptor subtypes. It is hoped that these studies on D2 receptor selective ligands will be useful in the future design of (a) receptor selective ligands used to define the function of D2-like receptor subtypes, (b) novel pharmacotherapeutic agents, and/or (c) in vitro and in vivo imaging agents. PMID:23259040

  11. Relationship of frontal D(2/3) binding potentials to cognition: a study of antipsychotic-naive schizophrenia patients.

    PubMed

    Fagerlund, Birgitte; Pinborg, Lars H; Mortensen, Erik Lykke; Friberg, Lars; Baaré, William F C; Gade, Anders; Svarer, Claus; Glenthøj, Birte Y

    2013-02-01

    Studies of in vivo dopamine receptors in schizophrenia have mostly focused on D(2) receptors in striatal areas or on D(1) receptors in cortex. No previous study has examined the correlation between cortical dopamine D(2/3) receptor binding potentials and cognition in schizophrenia patients. The objective was to examine this relation in the frontal cortex in first-episode, drug-naive schizophrenia patients. Based on preclinical and pharmacological evidence, we specifically expected to find a relation between D(2/3) receptor binding potentials and set shifting. This was a cross-sectional, case-control study using single-photon emission computerized tomography with the D(2/3)-receptor ligand [(123)I]epidepride, co-registered with structural magnetic resonance imaging and correlated to cognitive measures. Participants were 24 antipsychotic-naive, first-episode schizophrenia patients and 20 healthy controls matched for gender and age. For patients, a significant linear correlation between D(2/3) BP(ND) and set shifting was found, while significant quadratic associations were observed for verbal fluency, planning and attention. For controls, the only significant association with D(2/3) BP(ND) was a quadratic partial correlation for set shifting. The main findings indicated a relation between D(2/3) receptor binding in the frontal cortex and set shifting, planning and attention, but also support a differential involvement of cortical dopamine D(2/3) receptor binding in at least some cognitive functions, perhaps particularly attention, in schizophrenia patients compared to healthy people. The results suggest that cortical D(2/3) receptor function may be more involved in some cognitive functions (i.e. attention, fluency and planning) in patients with schizophrenia than in healthy people, suggesting that information processing in schizophrenia may be characterized by lower signal:noise ratios.

  12. D-amphetamine and antipsychotic drug effects on latent inhibition in mice lacking dopamine D2 receptors.

    PubMed

    Bay-Richter, C; O'Callaghan, M J; Mathur, N; O'Tuathaigh, C M P; Heery, D M; Fone, K C F; Waddington, J L; Moran, P M

    2013-07-01

    Drugs that induce psychosis, such as D-amphetamine (AMP), and those that alleviate it, such as antipsychotics, are suggested to exert behavioral effects via dopamine receptor D2 (D2). All antipsychotic drugs are D2 antagonists, but D2 antagonism underlies the severe and debilitating side effects of these drugs; it is therefore important to know whether D2 is necessary for their behavioral effects. Using D2-null mice (Drd2-/-), we first investigated whether D2 is required for AMP disruption of latent inhibition (LI). LI is a process of learning to ignore irrelevant stimuli. Disruption of LI by AMP models impaired attention and abnormal salience allocation consequent to dysregulated dopamine relevant to schizophrenia. AMP disruption of LI was seen in both wild-type (WT) and Drd2-/-. This was in contrast to AMP-induced locomotor hyperactivity, which was reduced in Drd2-/-. AMP disruption of LI was attenuated in mice lacking dopamine receptor D1 (Drd1-/-), suggesting that D1 may play a role in AMP disruption of LI. Further supporting this possibility, we found that D1 antagonist SKF83566 attenuated AMP disruption of LI in WT. Remarkably, both haloperidol and clozapine attenuated AMP disruption of LI in Drd2-/-. This demonstrates that antipsychotic drugs can attenuate AMP disruption of learning to ignore irrelevant stimuli in the absence of D2 receptors. Data suggest that D2 is not essential either for AMP to disrupt or for antipsychotic drugs to reverse AMP disruption of learning to ignore irrelevant stimuli and further that D1 merits investigation in the mediation of AMP disruption of these processes.

  13. Elevated Dopamine D2/3 Receptor Availability in Obese Individuals: A PET Imaging Study with [(11)C](+)PHNO.

    PubMed

    Gaiser, Edward C; Gallezot, Jean-Dominique; Worhunsky, Patrick D; Jastreboff, Ania M; Pittman, Brian; Kantrovitz, Lauren; Angarita, Gustavo A; Cosgrove, Kelly P; Potenza, Marc N; Malison, Robert T; Carson, Richard E; Matuskey, David

    2016-12-01

    Most prior work with positron emission tomography (PET) dopamine subtype 2/3 receptor (D2/3R) non-selective antagonist tracers suggests that obese (OB) individuals exhibit lower D2/3Rs when compared with normal weight (NW) individuals. A D3-preferring D2/3R agonist tracer, [(11)C](+)PHNO, has demonstrated that body mass index (BMI) was positively associated with D2/3R availability within striatal reward regions. To date, OB individuals have not been studied with [(11)C](+)PHNO. We assessed D2/3R availability in striatal and extrastriatal reward regions in 14 OB and 14 age- and gender-matched NW individuals with [(11)C](+)PHNO PET utilizing a high-resolution research tomograph. Additionally, in regions where group D2/3R differences were observed, secondary analyses of 42 individuals that constituted an overweight cohort was done to study the linear association between BMI and D2/3R availability in those respective regions. A group-by-brain region interaction effect (F7, 182=2.08, p=0.047) was observed. Post hoc analyses revealed that OB individuals exhibited higher tracer binding in D3-rich regions: the substantia nigra/ventral tegmental area (SN/VTA) (+20%; p=0.02), ventral striatum (VST) (+14%; p<0.01), and pallidum (+11%; p=0.02). BMI was also positively associated with D2/3R availability in the SN/VTA (r=0.34, p=0.03), VST (r=0.36, p=0.02), and pallidum (r=0.30, p=0.05) across all subjects. These data suggest that individuals who are obese have higher D2/3R availability in brain reward regions densely populated with D3Rs, potentially identifying a novel pharmacologic target for the treatment of obesity.

  14. Intracerebral Distribution of the Oncometabolite d-2-Hydroxyglutarate in Mice Bearing Mutant Isocitrate Dehydrogenase Brain Tumors: Implications for Tumorigenesis

    PubMed Central

    Pickard, Amanda J.; Sohn, Albert S. W.; Bartenstein, Thomas F.; He, Shan; Zhang, Yi; Gallo, James M.

    2016-01-01

    The prevalence of mutant isocitrate dehydrogenase 1 (IDH1) brain tumors has generated significant efforts to understand the role of the mutated enzyme product d-2-hydroxyglutarate (D2HG), an oncometabolite, in tumorigenesis, as well as means to eliminate it. Glymphatic clearance was proposed as a pathway that could be manipulated to accelerate D2HG clearance and dictated the study design that consisted of two cohorts of mice bearing U87/mutant IDH1 intracerebral tumors that underwent two microdialysis – providing D2HG interstitial fluid concentrations – sampling periods of awake and asleep (activate glymphatic clearance) in a crossover manner. Glymphatic clearance was found not to have a significant effect on D2HG brain tumor interstitial fluid concentrations that were 126.9 ± 74.8 μM awake and 117.6 ± 98.6 μM asleep. These concentrations, although low relative to total brain tumor concentrations of 6.8 ± 3.6 mM, were considered sufficient to be transported by interstitial fluid and taken up into normal cells to cause deleterious effects. A model of D2HG CNS distribution supported this contention and was further supported by in vitro studies that showed D2HG could interfere with immune cell function. The study provides insight into the compartmental distribution of D2HG in the brain, wherein the interstitial fluid serves as a dynamic pathway for D2HG to enter normal cells and contribute to tumorigenesis. PMID:27781195

  15. Adjuvant Chemotherapy for Elderly Patients with Gastric Cancer after D2 Gastrectomy

    PubMed Central

    Zhang, Dong-sheng; Ren, Chao; Bai, Long; Luo, Hui-yan; Wang, Zhi-qiang; Wang, Feng-hua; Li, Yu-hong; Xu, Rui-hua

    2013-01-01

    Background A phase III clinical trial has already shown the survival benefits of postoperative chemotherapy in gastric cancer. However, there are limited published data concerning the elderly. This study aims to investigate the use of adjuvant chemotherapy for gastric cancer after D2 gastrectomy among the elderly and identify its impact on survival. Methods We retrospectively reviewed 360 patients who had undergone D2 gastrectomy, aged 65 years or older, with non-metastatic gastric cancer in a single institution. We analyzed the predictors and survival benefits of adjuvant chemotherapy use in the elderly. Further, we analyzed the survival benefits of adjuvant chemotherapy by dividing the patients into groups according to disease stages and chemotherapeutic regimens. Results Among the 360 patients, only 34.7% of patients received adjuvant chemotherapy. Age, tumor location, lymph node involvement and tumor invasion were associated with the receipt of adjuvant chemotherapy. Adjuvant chemotherapy improved the overall survival for non-metastatic elderly patients (HR 0.60, 95%CI 0.42–0.83, P = 0.003). Significant survival benefits were found with adjuvant chemotherapy in stage III patients (HR 0.67, 95%CI 0.47–0.97, P = 0.033), but not in stage I patients or in stage II patients (HR 0.52, 95%CI 0.21–1.30 P = 0.161). Compared to adjuvant chemotherapy without platinum, no significant survival benefits were observed with platinum-containing chemotherapy (HR 0.84, 95%CI 0.49–1.45, P = 0.530). Besides adjuvant chemotherapy, other independent prognostic factors of survival included tumor location, tumor size, histologic grade, depth of tumor invasion, and lymph node status. Conclusions This study demonstrated the survival benefits of adjuvant fluoropyrimidine-based chemotherapy among the elderly patients with non-metastatic gastric cancer after D2 gastrectomy. However, due to the limitations of this study, further well-designed prospective studies with

  16. Adjuvant chemotherapy, p53, carcinoembryonic antigen expression and prognosis after D2 gastrectomy for gastric adenocarcinoma

    PubMed Central

    He, Ming-Ming; Zhang, Dong-Sheng; Wang, Feng; Wang, Zhi-Qiang; Luo, Hui-Yan; Ren, Chao; Jin, Ying; Chen, Dong-Liang; Xu, Rui-Hua

    2014-01-01

    AIM: To investigate adjuvant chemotherapy, p53 and carcinoembryonic antigen (CEA) expression and prognosis after D2 gastrectomy for stage II/III gastric adenocarcinoma. METHODS: A total of 286 patients with stage II or III gastric adenocarcinoma who underwent D2 radical gastrectomy between May 2007 and December 2010 were enrolled into this study. One hundred and sixty-nine of these patients received surgery plus adjuvant chemotherapy, and 117 patients received surgery alone. Tumor expression of p53 and CEA proteins in all patients was evaluated immunohistochemically and correlated with clinicopathological parameters. The Kaplan-Meier curves for overall survival (OS) and disease-free survival (DFS) with log-rank testing were used to compare the survival difference. A Cox proportional hazard regression model was used for multivariate analysis. RESULTS: Patients with adjuvant chemotherapy had a significantly better median OS (50.87 mo vs 30.73 mo, P = 0.000) and median DFS (36.30 mo vs 25.60 mo, P = 0.001) than patients with surgery alone in the entire cohort. Consistent results with the entire cohort were found in stage II (P = 0.006 and P = 0.047), stage III (P = 0.005 and P = 0.030), and stage IIIB/IIIC patients (P = 0.000 and P = 0.001). The median OS and DFS advantages were confirmed by multivariate analysis (P = 0.000 and P = 0.008) and maintained when the analyses were restricted to fluoropyrimidine monotherapy (P = 0.003 and P = 0.001) and fluoropyrimidine plus platinum regimen (P = 0.001 and P = 0.007), however, not the fluoropyrimidine plus taxane (P = 0.198 and P = 0.777) or platinum plus taxane (P = 0.666 and P = 0.687) regimens. Median OS and median DFS did not differ significantly between the patients with p53(+) and p53(-) tumors (P = 0.608 and P = 0.064), or between patients with CEA(+) and CEA(-) tumors (P = 0.052 and P = 0.989), which were maintained when the analyses were restricted to surgery alone (p53: P = 0.864 and P = 0.431; CEA: P = 0.142 and

  17. The Coxsackievirus and Adenovirus Receptor: Glycosylation and the Extracellular D2 Domain Are Not Required for Coxsackievirus B3 Infection

    PubMed Central

    Röger, Carsten; Kurreck, Jens; Bergelson, Jeffrey M.; Fechner, Henry

    2016-01-01

    ABSTRACT The coxsackievirus and adenovirus receptor (CAR) is a member of the immunoglobulin superfamily (IgSF) and functions as a receptor for coxsackie B viruses (CVBs). The extracellular portion of CAR comprises two glycosylated immunoglobulin-like domains, D1 and D2. CAR-D1 binds to the virus and is essential for virus infection; however, it is not known whether D2 is also important for infection, and the role of glycosylation has not been explored. To understand the function of these structural components in CAR-mediated CVB3 infection, we generated a panel of human (h) CAR deletion and substitution mutants and analyzed their functionality as CVB receptors, examining both virus binding and replication. Lack of glycosylation of the CAR-D1 or -D2 domains did not adversely affect CVB3 binding or infection, indicating that the glycosylation of CAR is not required for its receptor functions. Deletion of the D2 domain reduced CVB3 binding, with a proportionate reduction in the efficiency of virus infection. Replacement of D2 with the homologous D2 domain from chicken CAR, or with the heterologous type C2 immunoglobulin-like domain from IgSF11, another IgSF member, fully restored receptor function; however, replacement of CAR-D2 with domains from CD155 or CD80 restored function only in part. These data indicate that glycosylation of the extracellular domain of hCAR plays no role in CVB3 receptor function and that CAR-D2 is not specifically required. The D2 domain may function largely as a spacer permitting virus access to D1; however, the data may also suggest that D2 affects virus binding by influencing the conformation of D1. IMPORTANCE An important step in virus infection is the initial interaction of the virus with its cellular receptor. Although the role in infection of the extracellular CAR-D1, cytoplasmic, and transmembrane domains have been analyzed extensively, nothing is known about the function of CAR-D2 and the extracellular glycosylation of CAR. Our data

  18. A Method for Heat Treatment of Maraging Steels 08Kh15N5D2T, 06Kh14N6D2MBT, and 07Kh16N6

    NASA Astrophysics Data System (ADS)

    Il'in, A. A.; Krikushenko, E. S.; Alekseev, V. V.; Silina, V. I.; Belousov, V. V.

    2013-07-01

    A mode for heat treatment of maraging steels 08Kh15N5D2T, 06Kh14N6D2MBT and 07Kh16N6 is developed for critical parts and high-duty structures of "MiG" aircrafts operating under conditions of a complex stress state. The use of the method has made it possible to eliminate rejects and to raise the operational reliability of expensive articles.

  19. [Buspirone increases D2-like dopaminergic receptor density in rat corpus striatum].

    PubMed

    Lima, Vera Targino Moreira; Macedo, Danielle Silveira; Nogueira, Carlos Renato Alves; Vasconcelos, Silvânia Maria Mendes; Viana, Glauce Socorro de Barros; Sousa, Francisca Cléa Florenço de

    2002-03-01

    Buspirone (busp) a piperazinyl derivative with anxiolytic properties is a partial agonist on 5-HT1A with affinity for D2-like dopaminergic receptors (RD2). The objective of this study was to verify the effects of busp on RD2. Female Wistar rats 150-200 g were treated with busp (5 and 10 mg/kg, p.o.) 1 or 2 times daily for 7 days. Controls (C) received saline. The density of RD2 (fmol/mg protein) was determined through binding assays in striatum (ST) using [3H]-spiroperidol as radioligand. No alteration in Bmax or Kd values were seen after busp administration once a day. However, a RD2 upregulation of 55 % increase was observed after busp 2 times a day with no change in Kd values. The results showed that busp interact not only with serotonergic, but also with dopaminergic system.

  20. Preliminary Neutronic Study of D2O-cooled High Conversion PWRs

    SciTech Connect

    Hikaru Hiruta; Gilles Youinou

    2013-10-01

    This paper presents a preliminary neutronics analysis of tight-pitch D2O-cooled high-conversion PWRs loaded with MOX fuel aiming at high Pu conversion and negative void coefficient. SCALE6.1 has been exclusively utilized for this study. The analyses are performed in two separate parts. The first part of this paper investigates the performance of axial and internal blankets and seeks break-even or near-breeder core even without the presence of radial blankets. The second part of this paper performs sensitivity and uncertainty analyses of integral parameters (keff and void coefficient) for selected systems in order to analyze the characters of this high-conversion PWR from different aspects.

  1. Production of Atomic Hydrogen and Deuterium from H2, D2 and HD Photodissociation

    NASA Astrophysics Data System (ADS)

    Machacek, J. R.; Andrianarijaona, V. A.; Furst, J. E.; Gay, T. J.; Kilcoyne, A. L. D.; Landers, A. L.; Litaker, E. T.; McLaughlin, K. W.

    2010-03-01

    We have measured the production of Lyα and Hα fluorescence from atomic H and D resulting from the photodissociation of H2, D2 and HD by linearly-polarized photons with energies between 22 and 64 eV. In this energy range, excited photofragments result primarily from the production of doubly-excited molecular species which promptly autoionize or dissociate into two neutrals. Comparison between the current relative cross section results, previous absolute and relative experimental results and the available theory show only qualitative agreement. We will discuss the various systematic effects which affect this and other types of synchrotron-based measurements in this energy range. Support provided by the NSF (Grant PHY-0653379), DOE (LBNL/ALS) and ANSTO (Access to Major Research Facilities Programme).

  2. Competitive MS binding assays for dopamine D2 receptors employing spiperone as a native marker.

    PubMed

    Niessen, Karin V; Höfner, Georg; Wanner, Klaus T

    2005-10-01

    A competitive MS binding assay employing spiperone as a native marker and a porcine striatal membrane fraction as a source for dopamine D2 receptors in a nonvolatile buffer has been established. Binding of the test compounds to the target was monitored by mass-spectrometric quantification of the nonbound marker, spiperone, in the supernatant of the binding samples obtained by centrifugation. A solid-phase extraction procedure was used for separating spiperone from ESI-MS-incompatible supernatant matrix components. Subsequently, the marker was reliably quantified by LC-ESI-MS-MS by using haloperidol as an internal standard. The affinities of the test compounds, the dopamine receptor antagonists (+)-butaclamol, chlorpromazine and (S)-sulpiride obtained from the competitive MS binding assay were verified by corresponding radioligand binding experiments with [3H]spiperone. The results of this study demonstrate that competitive MS binding assays represent a universally applicable alternative to conventional radioligand binding assays.

  3. Acoustic Emission Methodology to Evaluate the Fracture Toughness in Heat Treated AISI D2 Tool Steel

    NASA Astrophysics Data System (ADS)

    Mostafavi, Sajad; Fotouhi, Mohamad; Motasemi, Abed; Ahmadi, Mehdi; Sindi, Cevat Teymuri

    2012-10-01

    In this article, fracture toughness behavior of tool steel was investigated using Acoustic Emission (AE) monitoring. Fracture toughness ( K IC) values of a specific tool steel was determined by applying various approaches based on conventional AE parameters, such as Acoustic Emission Cumulative Count (AECC), Acoustic Emission Energy Rate (AEER), and the combination of mechanical characteristics and AE information called sentry function. The critical fracture toughness values during crack propagation were achieved by means of relationship between the integral of the sentry function and cumulative fracture toughness (KICUM). Specimens were selected from AISI D2 cold-work tool steel and were heat treated at four different tempering conditions (300, 450, 525, and 575 °C). The results achieved through AE approaches were then compared with a methodology proposed by compact specimen testing according to ASTM standard E399. It was concluded that AE information was an efficient method to investigate fracture characteristics.

  4. Electrofusion of plant cell protoplasts under microgravity--a D-2 spacelab experiment.

    PubMed

    Hoffmann, E; Schonherr, K; Johann, P; Hampp, R; von Keller, A; Voeste, D; Barth, S; Schnabl, H; Baumann, T; Eisenbeiss, M; Reinhard, E

    1995-11-01

    Plant cell protoplasts, derived from sexually incompatible plant species, have proved to be a good system for somatic hybridization by electrofusion. Under microgravity, an increase in fusion yield can be expected, especially if the parental cells differ markedly in size or specific density. On the D-2 spacelab mission flown in 1993, electrofusion experiments were performed with three different objects, i.e. tobacco as model system, Helianthus as an important crop, and Digitalis as a plant of pharmacological interest. The resulting fusion products were cultivated (along with parental cells) for 10 days under microgravity, and subsequently regenerated on ground for biochemical analysis. Results are presented on the observation of the fusion process during flight, heterofusion yields, ultrastructural investigation of fusion products immediately after fusion, and characterization of the resulting hybrids. The results are interpreted on the background of earlier microgravity-experiments on sounding rockets or parabolic flights.

  5. D2 receptor blockade by flunarizine and cinnarizine explains extrapyramidal side effects. A SPECT study.

    PubMed

    Brücke, T; Wöber, C; Podreka, I; Wöber-Bingöl, C; Asenbaum, S; Aull, S; Wenger, S; Ilieva, D; Harasko-van der Meer, C; Wessely, P

    1995-05-01

    Twenty-six patients under treatment with the calcium channel blockers flunarizine (Fz) or cinnarizine (Cz) were examined-with single-photon emission computed tomography using [123I]iodobenzamide as a ligand. The striatal dopamine D2 receptor-binding potential was determined and found to be reduced by 14 to 63% (39.5 +/- 15.0%; p < 0.0001) in patients compared with age-matched control values. This reduction was larger in 12 patients with extrapyramidal symptoms and was only slowly reversible after discontinuation of treatment. Patients treated for > 6 months had significantly larger reductions than patients treated for a shorter period. Parkinsonian symptoms were only seen in patients older than 50 years. Our findings prove a neuroleptic-like action of Fz and Cz, which seems to be the major reason for their extrapyramidal side effects. Older age and long-term treatment are predisposing factors for these effects.

  6. Microbiological analysis of debris from Space Transportation System (STS)-55 Spacelab D-2

    NASA Technical Reports Server (NTRS)

    Huff, T. L.

    1994-01-01

    Filter debris from the Spacelab module D-2 of STS-55 was analyzed for microbial contamination. Debris from cabin and avionics filters was collected by Kennedy Space Center personnel on May 8, 1993, 2 days postflight. Debris weights were similar to those of previous Spacelab missions. Approximately 5.1E+5 colony forming units per gram of debris were enumerated from the cabin and avionics filter debris, respectively. these numbers were similar in previous missions for which the entire contents were analyzed without sorting of the material. Bacterial diversity was small compared to previous missions, with no gram negative bacteria isolated. Only one bacterial species, Corynebacterium pseudodiphtheriticum, was not isolated previously by the laboratory from Spacelab debris. This organism is a normal inhabitant of the pharynx. A table listing all species of bacteria isolated by the laboratory from previous Spacelab air filters debris collection is provided.

  7. The impact of specular highlights on 3D-2D face recognition

    NASA Astrophysics Data System (ADS)

    Christlein, Vincent; Riess, Christian; Angelopoulou, Elli; Evangelopoulos, Georgios; Kakadiaris, Ioannis

    2013-05-01

    One of the most popular form of biometrics is face recognition. Face recognition techniques typically assume that a face exhibits Lambertian reectance. However, a face often exhibits prominent specularities, especially in outdoor environments. These specular highlights can compromise an identity authentication. In this work, we analyze the impact of such highlights on a 3D-2D face recognition system. First, we investigate three different specularity removal methods as preprocessing steps for face recognition. Then, we explicitly model facial specularities within the face detection system with the Cook-Torrance reflectance model. In our experiments, specularity removal increases the recognition rate on an outdoor face database by about 5% at a false alarm rate of 10-3. The integration of the Cook-Torrance model further improves these results, increasing the verification rate by 19% at a FAR of 10-3.

  8. Raman spectroscopy of gases with a Fourier transform spectrometer: the spectrum of D2

    SciTech Connect

    Jennings, D.E.; Weber, A.; Brault, J.W.

    1986-01-15

    A high-resolution Fourier transform spectrometer (FTS) has been used to record spontaneous incoherent laser Raman spectra of gases. The resolution, sensitivity, calibration accuracy, and spectral coverage achieved in these spectra demonstrate the viability of the FTS for Raman spectroscopy. Measurements from a spectrum of D2 containing both v = 0-0 and v = 1-0 transitions were fitted to the Dunham expansion of the vibration--rotation energy levels. The coefficients are (in cm ) Y10 = 2993.6060(67), Y01 = 30.4401 (89), Y11 = -1.0538(17), Y02 = -0.011590(41), Y12 = 2.02(80) x 10 U, and Y03 = 5.83(11) x 10 W. Errors in parentheses are one standard deviation.

  9. Quantum interference between H + D2 quasiclassical reaction mechanisms.

    PubMed

    Jambrina, Pablo G; Herráez-Aguilar, Diego; Aoiz, F Javier; Sneha, Mahima; Jankunas, Justinas; Zare, Richard N

    2015-08-01

    Interferences are genuine quantum phenomena that appear whenever two seemingly distinct classical trajectories lead to the same outcome. They are common in elastic scattering but are seldom observable in chemical reactions. Here we report experimental measurements of the state-to-state angular distribution for the H + D2 reaction using the 'photoloc' technique. For products in low rotational and vibrational states, a characteristic oscillation pattern governs backward scattering. The comparison between the experiments, rigorous quantum calculations and classical trajectories on an accurate potential energy surface allows us to trace the origin of that structure to the quantum interference between different quasiclassical mechanisms, a phenomenon analogous to that observed in the double-slit experiment.

  10. Influence of the Reactants Rotational Excitation on the H + D2(v = 0, j) Reactivity.

    PubMed

    Aldegunde, J; Jambrina, P G; González-Sanchez, L; Herrero, V J; Aoiz, F J

    2015-12-17

    We have analyzed the influence of the rotational excitation on the H + D2(v = 0, j) reaction through quantum mechanical (QM) and quasiclassical trajectories (QCT) calculations at a wide range of total energies. The agreement between both types of calculations is excellent. We have found that the rotational excitation largely increases the reactivity at large values of the total energy. Such an increase cannot be attributed to a stereodynamical effect but to the existence of recrossing trajectories that become reactive as the target molecule gets rotationally excited. At low total energies, however, recrossing is not significant and the reactivity evolution is dominated by changes in the collision energy; the reactivity decreases with the collision energy as it shrinks the acceptance cone. When state-to-state results are considered, rotational excitation leads to cold product's rovibrational distributions, so that most of the energy is released as recoil energy.

  11. STS-55 Columbia, Orbiter Vehicle (OV) 102, Spacelab D2 Official crew portrait

    NASA Technical Reports Server (NTRS)

    1993-01-01

    STS-55 Columbia, Orbiter Vehicle (OV) 102, crewmembers, wearing their launch and entry suits (LESs), pose for their Official crew portrait. Five NASA astronauts and two German payload specialists, assigned to fly aboard OV-102 in support of Spacelab Deutsche 2 (SL-D2), are pictured. On the front row (left to right) are Pilot Terence T. Henricks (holding launch and entry helmet (LEH)), Commander Steven R. Nagel (holding crew insignia), and Mission Specialist 2 (MS2) Charles J. Precourt (holding LEH). In the back are (left to right) MS3 Bernard A. Harris, Jr, Payload Specialist 2 Hans Schlegel, MS and Payload Commander (PLC) Jerry L. Ross, and Payload Specialist 1 Ulrich Walter. In the background are the United States and German flags. Portrait made by NASA JSC contract photographer Robert L. Walck.

  12. STS-55 Pilot Henricks uses CTE equipment mounted on SL-D2 aft end cone

    NASA Technical Reports Server (NTRS)

    1993-01-01

    STS-55 Pilot Terence T. Henricks, positioned in front of an adjustable workstation mounted on the Spacelab Deutsche 2 (SL-D2) science module aft end cone, conducts Crew Telesupport Experiment (CTE). The STS-55 crew portrait (STS055(S)002) appears on the screen of the Macintosh portable computer. CTE will demonstrate real-time communication between the shuttle crew and the ground via a computer-based multimedia documentation file that includes text, graphics, and photos. CTE is expected to improve the effectiveness of on-orbit payload operations, returns from scientific investigations, crew interaction with the ground, and contingency maintenance tasks for systems and payloads. Also in the view and attached to the end cone are a fire extinguisher, a checklist, and an STS-37 extravehicular activity (EVA) photo of Mission Specialist (MS1) and Payload Commander (PLC) Jerry L. Ross (STS037-18-032).

  13. Inönü-Wigner contraction and D=2+1 supergravity

    NASA Astrophysics Data System (ADS)

    Concha, P. K.; Fierro, O.; Rodríguez, E. K.

    2017-01-01

    We present a generalization of the standard Inönü-Wigner contraction by rescaling not only the generators of a Lie superalgebra but also the arbitrary constants appearing in the components of the invariant tensor. The procedure presented here allows one to obtain explicitly the Chern-Simons supergravity action of a contracted superalgebra. In particular we show that the Poincaré limit can be performed to a D=2+1 ( p,q) AdS Chern-Simons supergravity in presence of the exotic form. We also construct a new three-dimensional ( 2,0) Maxwell Chern-Simons supergravity theory as a particular limit of ( 2,0) AdS-Lorentz supergravity theory. The generalization for N=p+q gravitinos is also considered.

  14. IRIS : A reaction spectroscopy facility with solid H2 /D2 target

    NASA Astrophysics Data System (ADS)

    Holl, Matthias; Kanungo, Ritu; Alcorta, Martin; Andreoiu, Corina; Bidaman, Harris; Burbadge, Christina; Burke, Devin; Chen, Alan; Davids, Barry; Diaz Varela, Alejandra; Garrett, Paul; Hackman, Greg; Ishimoto, Shigeru; Kaur, Satbir; Keefe, Matthew; Kruecken, Reiner; Mansour, Iymad; Randhawa, Jaspreet; Sanetullaev, Alisher; Shotter, Alan; Smith, Jenna; Tanaka, Junki; Tanihata, Isao; Turko, Joseph; Workman, Orry

    2016-09-01

    The charged particle reaction spectroscopy station IRIS at TRIUMF is designed to allow studies of inelastic scattering and transfer reactions for low intensity beams. To do so, a novel solid H2 /D2 target is used in combination with a low pressure ionization chamber for the identification of incoming beam particles. The light ejectiles are measured using a ΔE - E telescope consisting of an annular silicon detector followed by CsI(Tl) array. Another ΔE - E telescope, consisting of two segmented silicon detectors, is used to identify the heavy outgoing particles. An overview of the faciltity will be given and examples from recent experiments that illustrate that facility's capability for reaction studies of exotic nuclei will be shown. Support from Canada Foundation for Innovation, Nova Scotia Research and Innovation Trust and NSERC.

  15. Competition between charge exchange and chemical reaction - The D2/+/ + H system

    NASA Technical Reports Server (NTRS)

    Preston, R. K.; Cross, R. J., Jr.

    1973-01-01

    Study of the special features of molecular charge exchange and its competition with chemical reaction in the case of the D2(+) + H system. The trajectory surface hopping (TSH) model proposed by Tully and Preston (1971) is used to study this competition for a number of reactions involving the above system. The diatomics-in-molecules zero-overlap approximation is used to calculate the three adiabatic surfaces - one triplet and two singlet - which are needed to describe this system. One of the significant results of this study is that the chemical reaction and charge exchange are strongly coupled. It is also found that the number of trajectories passing into the chemical regions of the three surfaces depends very strongly on the surface crossings.-

  16. Influence of the Reactants Rotational Excitation on the H+D2(v=0, j) Reactivity

    PubMed Central

    Aldegunde, J; Jambrina, PG; González-Sanchez, L; Herrero, VJ; Aoiz, FJ

    2016-01-01

    We have analyzed the influence of the rotational excitation on the H+D2(υ=0, j) reaction through quantum mechanical (QM) and quasiclassical trajectories (QCT) calculations at a wide range of total energies. The agreement between both types of calculations is excellent. We have found that the rotational excitation largely increases the reactivity at large values of the total energy. Such increase cannot be attributed to a stereodynamical effect but to the existence of recrossing trajectories that become reactive as the target molecule gets rotationally excited. At low total energies, however, recrossing is not significant and the reactivity evolution is dominated by changes in the collision energy; the reactivity decreases with the collision energy as it shrinks the acceptance cone. When state-to-state results are considered, rotational excitation leads to cold product’s rovibrational distributions, so that most of the energy is released as recoil energy. PMID:26305719

  17. High-resolution FTIR measurement of the ν4 band of methylene fluoride-d 2

    NASA Astrophysics Data System (ADS)

    Shastri, Aparna; Deo, M. N.; Kawaguchi, K.

    2004-10-01

    A high-resolution (0.002 cm -1) infrared absorption spectrum of methylene fluoride-d 2 (CD 2F 2) of the lowest fundamental mode ν4 in the region from 460 to 610 cm -1 has been measured on a Bruker IFS 120-HR Fourier transform infrared spectrometer. More than 3500 transitions have been assigned in this B-type band centered at 521.9 cm -1. The data have been combined with upper state pure rotational measurements in a weighted least-squares fit to obtain molecular constants for the upper state resulting in an overall standard deviation of 0.00018 cm -1. Accurate value for the band origin (521.9578036 cm -1) has been obtained and inclusion of transitions with very high J (⩽60) and Ka (⩽34) values has resulted in improved precision for sextic centrifugal distortion constants, in particular DK, HKJ, and HK.

  18. Unitarity of spin-2 theories with linearized Weyl symmetry in D=2+1 dimensions

    SciTech Connect

    Dalmazi, D.

    2009-10-15

    Here we prove unitarity of the recently found fourth-order (in derivatives) self-dual model of spin-2 by investigating the analytic structure of its propagator. The model describes massive particles of helicity +2 (or -2) in D=2+1 dimensions and corresponds to the quadratic truncation of a higher derivative topologically massive gravity about a flat background. It is an intriguing example of a theory where a term in the propagator of the form 1/[{open_square}{sup 2}({open_square}-m{sup 2})] does not lead to ghosts. The crucial role of the linearized Weyl symmetry in getting rid of the ghosts is pointed out. We use a peculiar pair of gauge conditions which fix the linearized reparametrizations and linearized Weyl symmetries separately.

  19. STS-55 SL-D2 crew, in LESs, rehearse launch procedures during TCDT at KSC

    NASA Technical Reports Server (NTRS)

    1993-01-01

    STS-55 Columbia, Orbiter Vehicle (OV) 102, Spacelab Deutsche 2 (SL-D2) crewmembers, wearing launch and entry suits (LESs), depart the Operations and Checkout (O and C) Building for Kennedy Space Center (KSC) Launch Complex (LC) Pad 39A. Leading the way are Pilot Terence T. Henricks (left) and Commander Steven R. Nagel; behind them are, from left Mission Specialist 2 (MS2) Charles J. Precourt, MS3 Bernard A. Harris, Jr, MS1 and Payload Commander (PLC) Jerry L. Ross, German Payload Specialist 1 Ulrich Walter, and German Payload Specialist 2 Hans Schlegel. This is the final portion of the Terminal Countdown Demonstration Test (TCDT), a dress rehearsal for launch which cumulates with a simulated T-0. View provided by KSC with alternate KSC number KSC-93PC-310.

  20. Agentic extraversion modulates the cardiovascular effects of the dopamine D2 agonist bromocriptine.

    PubMed

    Wacker, Jan; Stemmler, Gerhard

    2006-07-01

    A recent psychobiological theory postulates a dopaminergic basis for the agency facet of extraversion, leading to the prediction that this personality trait modulates the psychophysiological effects of dopaminergic drugs. A single dose of the dopamine D2 receptor agonist bromocriptine reduces blood pressure in healthy volunteers. However, it is currently unknown whether this hypotensive effect of bromocriptine is modulated by agentic extraversion. Therefore, we measured resting cardiovascular activation in groups of healthy male volunteers either high or low in agentic extraversion, either under bromocriptine (1.25 mg) or placebo. Focusing the analyses on activation components derived from 18 cardiovascular variables, we found that bromocriptine reduces alpha-adrenergic activation in the sample as a whole, whereas the effects on beta-adrenergic and cholinergic activation are modulated by agentic extraversion.

  1. A Web-Based Climate Change Drought Decision Support System (C2D2S2)

    NASA Astrophysics Data System (ADS)

    Aggett, G. R.

    2008-12-01

    Water managers are increasingly recognizing climate change as a significant issue and are requesting detailed information about potential hydrologic impacts suitable for inclusion in planning. For operational forecasts of streamflow, physically-based hydrologic models that can integrate critical parameters from climate change forecasts are required, as they can be used to directly relate altered temperature regimes to changes in snowpack, streamflow timing, and other effects. Available studies, however, are most often academic in nature and have the added limitation of being incompatible with agency specific water management models or the streamflow period of interest. Commissioning of a study focused on a specific system is generally prohibitively expensive for most municipalities and agencies. This study thus focused on the design and development of a prototype web-based Climate Change Drought Decision Support System (C2D2S2) to enable water managers at various operational- and time-scales to rapidly assess the impact of predicted climate change on natural flows at critical nodes along a river network. Results presented here highlight development of the system, specifically determination of the full range of elements required to build and support C2D2S2 including data, methods, tools and infrastructure necessary to power a full system capable of providing widespread and low-cost access to tools that can be used to generate scenarios of future streamflow over the internet. Results also stress the need for close interaction with, and feedback from stakeholders during development. This participation is critical to ensure potential users can use the tool effectively, and that data products are understandable in the context of operational water management decisions.

  2. Lacunarity analysis of raster datasets and 1D, 2D, and 3D point patterns

    NASA Astrophysics Data System (ADS)

    Dong, Pinliang

    2009-10-01

    Spatial scale plays an important role in many fields. As a scale-dependent measure for spatial heterogeneity, lacunarity describes the distribution of gaps within a set at multiple scales. In Earth science, environmental science, and ecology, lacunarity has been increasingly used for multiscale modeling of spatial patterns. This paper presents the development and implementation of a geographic information system (GIS) software extension for lacunarity analysis of raster datasets and 1D, 2D, and 3D point patterns. Depending on the application requirement, lacunarity analysis can be performed in two modes: global mode or local mode. The extension works for: (1) binary (1-bit) and grey-scale datasets in any raster format supported by ArcGIS and (2) 1D, 2D, and 3D point datasets as shapefiles or geodatabase feature classes. For more effective measurement of lacunarity for different patterns or processes in raster datasets, the extension allows users to define an area of interest (AOI) in four different ways, including using a polygon in an existing feature layer. Additionally, directionality can be taken into account when grey-scale datasets are used for local lacunarity analysis. The methodology and graphical user interface (GUI) are described. The application of the extension is demonstrated using both simulated and real datasets, including Brodatz texture images, a Spaceborne Imaging Radar (SIR-C) image, simulated 1D points on a drainage network, and 3D random and clustered point patterns. The options of lacunarity analysis and the effects of polyline arrangement on lacunarity of 1D points are also discussed. Results from sample data suggest that the lacunarity analysis extension can be used for efficient modeling of spatial patterns at multiple scales.

  3. Exposure to D2-like dopamine receptor agonists inhibits swimming in Daphnia magna.

    PubMed

    Barrozo, Enrico R; Fowler, David A; Beckman, Matthew L

    2015-10-01

    Daphnia are freshwater crustaceans that have been used for decades in ecotoxicology research. Despite the important role that Daphnia have played in environmental toxicology studies, very little is known about the neurobiology of Daphnia. Although many studies have investigated the swimming movements of these "water fleas", few studies have examined the underlying neurochemical basis for these movements. To characterize the locomotor effect of drugs in Daphnia, a two-dimensional video imaging tool was developed and animal tracking was performed with freely available software, CTRAX. Due to the central role that dopamine plays in the movement of animals, we sought to determine the role of dopamine receptor signaling in Daphnia movement by characterizing the effect of ten drugs that are agonists or antagonists of dopamine receptors. At 1, 2, and 6h of treatment with a 10μM drug, several dopamine receptor agonists with documented effects on the D2-like class of receptors decreased the movement. Further, we determined behavioral inhibition values (IC50) at 1h of treatment for (1R,3S)-1-(aminomethyl)-3-phenyl-3,4-dihydro-1H-isochromene-5,6-diol (A68930) to be 1.4μM and for bromocriptine to be 6.6μM. This study describes a new method to study Daphnia swimming and establishes this organism as a useful model for studies of dopaminergic signaling. Specifically, this study shows that a dopamine receptor signaling pathway, mediated by putative D2-like receptors, is involved in the control of Daphnia swimming behavior. Due to its ease of use and its rich motor program we propose that Daphnia should be considered for future studies of dopamine neuron toxicity and protection.

  4. Dopamine D2 receptor imaging with SPECT: Studies in different neuropsychiatric disorders

    SciTech Connect

    Bruecke, T.P.; Podreka, I.; Angelberger, P.; Wenger, S.; Topitz, A.; Kuefferle, B.M.; Mueller, C.D.; Deecke, L. )

    1991-03-01

    The purpose of the present study is to visualize and quantify dopamine D2 receptors in the living human brain using an 123I-labeled ligand and the single photon emission computerized tomography (SPECT) technique. S-(-)-Iodobenzamide (S-(-)-IBZM) has been shown to be a highly selective ligand with high affinity for D2 receptors in experimental studies. Five millicuries (185 MBq) of 123I-labeled S-(-)-IBZM was administered intravenously to 12 control subjects, 22 parkinsonian patients under L-Dopa therapy, 12 parkinsonian patients without L-Dopa, 10 unmedicated patients with Huntington's disease, and 12 patients under different neuroleptics. Data collection with a rotating double-head scintillation camera started 1 h after injection and lasted for 50 min. In a semiquantitative approach, a ratio was calculated between mean counts per pixel in the striatum and a region in the lateral frontal cortex, which was 1.74 +/- 0.10 in the control group. A marked reduction of this ratio was found in patients with Huntington's disease (1.38 +/- 0.12; p = 0.0001), no significant changes in untreated parkinsonian patients (1.67 +/- 0.14), but a reduction in L-Dopa-treated cases (1.59 +/- 0.13; p = 0.0014). A curvilinear relationship was found between total daily dose of neuroleptics and the reduction of this ratio. Estimated receptor blockade under full neuroleptic treatment was 75-80%. S-(-)-IBZM binding was reduced with increasing age (p less than 0.01). Specific binding was reduced markedly when the racemic mixture of IBZM was used, and no specific binding was seen with the R-(+)-isomer, demonstrating the stereoselectivity of IBZM binding.

  5. Cabergoline, Dopamine D2 Receptor Agonist, Prevents Neuronal Cell Death under Oxidative Stress via Reducing Excitotoxicity

    PubMed Central

    Odaka, Haruki; Numakawa, Tadahiro; Adachi, Naoki; Ooshima, Yoshiko; Nakajima, Shingo; Katanuma, Yusuke; Inoue, Takafumi; Kunugi, Hiroshi

    2014-01-01

    Several lines of evidence demonstrate that oxidative stress is involved in the pathogenesis of neurodegenerative diseases, including Parkinson's disease. Potent antioxidants may therefore be effective in the treatment of such diseases. Cabergoline, a dopamine D2 receptor agonist and antiparkinson drug, has been studied using several cell types including mesencephalic neurons, and is recognized as a potent radical scavenger. Here, we examined whether cabergoline exerts neuroprotective effects against oxidative stress through a receptor-mediated mechanism in cultured cortical neurons. We found that neuronal death induced by H2O2 exposure was inhibited by pretreatment with cabergoline, while this protective effect was eliminated in the presence of a dopamine D2 receptor inhibitor, spiperone. Activation of ERK1/2 by H2O2 was suppressed by cabergoline, and an ERK signaling pathway inhibitor, U0126, similarly protected cortical neurons from cell death. This suggested the ERK signaling pathway has a critical role in cabergoline-mediated neuroprotection. Furthermore, increased extracellular levels of glutamate induced by H2O2, which might contribute to ERK activation, were reduced by cabergoline, while inhibitors for NMDA receptor or L-type Ca2+ channel demonstrated a survival effect against H2O2. Interestingly, we found that cabergoline increased expression levels of glutamate transporters such as EAAC1. Taken together, these results suggest that cabergoline has a protective effect on cortical neurons via a receptor-mediated mechanism including repression of ERK1/2 activation and extracellular glutamate accumulation induced by H2O2. PMID:24914776

  6. Novel quasi-subgenotype D2 of hepatitis B virus identified in Taiwanese aborigines.

    PubMed

    Tran, Huy; Yu, Ming-Lung; Dai, Chia-Yen; Lin, I-Ling; Yeh, Ming-Lun; Chuang, Wan-Long; Abe, Kenji

    2014-08-01

    The hepatitis B virus (HBV) genomes in Taiwanese aborigines, whose ancestors have lived in Taiwan for over 10,000 years, have not been characterized. In order to characterize of HBV in this special population, serum samples were obtained from serologically HBsAg-positive 27 Taiwanese aborigines. The pre-S1/S2 region and the full-length 3.2 kb of the HBV genome were amplified by PCR. Obtained amplicons were sequenced and confirmed the HBV genotypes by phylogenetic analysis. By phylogenetic analysis of the sequence of pre-S1/pre-S2 region, HBV/B2 (21/27: 78 %) was the most prevalent followed by genotype D (6/27: 22 %). Two strains of HBV/B2, each having 3,215 bp genomes, had recombination with genotype C in the pre-C/C gene which is characteristic of subgenotype B2 circulating in Southeast Asia. Interestingly, six strains of genotype D formed a distinct cluster between subgenotypes D1 and D2 suggesting a novel group of HBV. A similar finding could also be confirmed based on the entire 3,182 bp genome from four strains of HBV/D. This new cluster was supported by a branch with 99 % bootstrap value and 3.4-5.8 % nucleotide divergence over the entire genome from other known subgenotypes D1 to D9. Four strains of the new D subgenotype showed serotype ayw2, but had unique amino acid sequences consisting of N115 in the preS/S gene; P41 in the X gene; S239, K/E295, V567, and P708 in the P gene, respectively. From the above results, we provisionally proposed to designate it as novel quasi-subgenotype D2 identified in Taiwanese aborigines.

  7. Temperature dependence of vibrational frequency fluctuation of N3- in D2O

    NASA Astrophysics Data System (ADS)

    Tayama, Jumpei; Ishihara, Akane; Banno, Motohiro; Ohta, Kaoru; Saito, Shinji; Tominaga, Keisuke

    2010-07-01

    We have studied the temperature dependence of the vibrational frequency fluctuation of the antisymmetric stretching mode of N3- in D2O by three-pulse infrared (IR) photon echo experiments. IR pump-probe measurements were also carried out to investigate the population relaxation and the orientational relaxation of the same band. It was found that the time-correlation function (TCF) of the frequency fluctuation of this mode is well described by a biexponential function with a quasistatic term. The faster decay component has a time constant of about 0.1 ps, and the slower component varies from 1.4 to 1.1 ps in the temperature range from 283 to 353 K. This result indicates that liquid dynamics related to the frequency fluctuation are not highly sensitive to temperature. We discuss the relationship between the temperature dependence of the vibrational frequency fluctuation and that of the molecular motion of the system to investigate the molecular origin of the frequency fluctuation of the solute. We compare the temperature dependence of the frequency fluctuation with that of other dynamics such as dielectric relaxation of water. In contrast to the Debye dielectric relaxation time of D2O, the two time constants of the TCF of the frequency fluctuation do not exhibit strong temperature dependence. We propose a simple theoretical model for the frequency fluctuation in solutions based on perturbation theory and the dipole-dipole interaction between the vibrational mode of the solute and the solvent molecules. This model suggests that the neighboring solvent molecules in the vicinity of the solute play an important role in the frequency fluctuation. We suggest that the picosecond component of the frequency fluctuation results from structural fluctuation of the hydrogen-bonding network in water.

  8. STS-55 MS3 Harris conducts HOLOP experiment at SL-D2 Rack 11 aboard OV-102

    NASA Technical Reports Server (NTRS)

    1993-01-01

    STS-55 Mission Specialist 3 (MS3) Bernard A. Harris, Jr works at Spacelab Deutsche 2 (SL-D2) Rack 11 with the Holographic Optics Laboratory (HOLOP) aboard the Earth-orbiting Columbia, Orbiter Vehicle (OV) 102.

  9. The identification of a selective dopamine D2 partial agonist, D3 antagonist displaying high levels of brain exposure.

    PubMed

    Holmes, Ian P; Blunt, Richard J; Lorthioir, Olivier E; Blowers, Stephen M; Gribble, Andy; Payne, Andrew H; Stansfield, Ian G; Wood, Martyn; Woollard, Patrick M; Reavill, Charlie; Howes, Claire M; Micheli, Fabrizio; Di Fabio, Romano; Donati, Daniele; Terreni, Silvia; Hamprecht, Dieter; Arista, Luca; Worby, Angela; Watson, Steve P

    2010-03-15

    The identification of a highly selective D(2) partial agonist, D(3) antagonist tool molecule which demonstrates high levels of brain exposure and selectivity against an extensive range of dopamine, serotonin, adrenergic, histamine, and muscarinic receptors is described.

  10. The Agrobacterium tumefaciens virulence D2 protein is responsible for precise integration of T-DNA into the plant genome.

    PubMed Central

    Tinland, B; Schoumacher, F; Gloeckler, V; Bravo-Angel, A M; Hohn, B

    1995-01-01

    The VirD2 protein of Agrobacterium tumefaciens was shown to pilot T-DNA during its transfer to the plant cell nucleus. We analyze here its participation in the integration of T-DNA by using a virD2 mutant. This mutation reduces the efficiency of T-DNA transfer, but the efficiency of integration of T-DNA per se is unaffected. Southern and sequence analyses of integration events obtained with the mutated VirD2 protein revealed an aberrant pattern of integration. These results indicate that the wild-type VirD2 protein participates in ligation of the 5'-end of the T-strand to plant DNA and that this ligation step is not rate limiting for T-DNA integration. Images PMID:7628458

  11. In vivo production of novel vitamin D2 hydroxy-derivatives by human placentas, epidermal keratinocytes, Caco-2 colon cells and the adrenal gland

    PubMed Central

    Slominski, Andrzej T.; Kim, Tae-Kang; Shehabi, Haleem Z.; Tang, Edith; Benson, Heather A. E.; Semak, Igor; Lin, Zongtao; Yates, Charles R.; Wang, Jin; Li, Wei; Tuckey, Robert C.

    2014-01-01

    We investigated the metabolism of vitamin D2 to hydroxyvitamin D2 metabolites ((OH)D2) by human placentas ex-utero, adrenal glands ex-vivo and cultured human epidermal keratinocytes and colonic Caco-2 cells, and identified 20(OH)D2, 17,20(OH)2D2, 1,20(OH)2D2, 25(OH)D2 and 1,25(OH)2D2 as products. Inhibition of product formation by 22R-hydroxycholesterol indicated involvement of CYP11A1 in 20- and 17-hydroxylation of vitamin D2, while use of ketoconazole indicated involvement of CYP27B1 in 1α-hydroxylation of products. Studies with purified human CYP11A1 confirmed the ability of this enzyme to convert vitamin D2 to 20(OH)D2 and 17,20(OH)2D2. In placentas and Caco-2 cells, production of 20(OH)D2 was higher than 25(OH)D2 while in human keratinocytes the production of 20(OH)D2 and 25(OH)D2 were comparable. HaCaT keratinocytes showed high accumulation of 1,20(OH)2D2 relative to 20(OH)D2 indicating substantial CYP27B1 activity. This is the first in vivo evidence for a novel pathway of vitamin D2 metabolism initiated by CYP11A1 and modified by CYP27B1, with the product profile showing tissue- and cell-type specificity. PMID:24382416

  12. In vivo production of novel vitamin D2 hydroxy-derivatives by human placentas, epidermal keratinocytes, Caco-2 colon cells and the adrenal gland.

    PubMed

    Slominski, Andrzej T; Kim, Tae-Kang; Shehabi, Haleem Z; Tang, Edith K Y; Benson, Heather A E; Semak, Igor; Lin, Zongtao; Yates, Charles R; Wang, Jin; Li, Wei; Tuckey, Robert C

    2014-03-05

    We investigated the metabolism of vitamin D2 to hydroxyvitamin D2 metabolites ((OH)D2) by human placentas ex-utero, adrenal glands ex-vivo and cultured human epidermal keratinocytes and colonic Caco-2 cells, and identified 20(OH)D2, 17,20(OH)₂D2, 1,20(OH)₂D2, 25(OH)D2 and 1,25(OH)₂D2 as products. Inhibition of product formation by 22R-hydroxycholesterol indicated involvement of CYP11A1 in 20- and 17-hydroxylation of vitamin D2, while use of ketoconazole indicated involvement of CYP27B1 in 1α-hydroxylation of products. Studies with purified human CYP11A1 confirmed the ability of this enzyme to convert vitamin D2 to 20(OH)D2 and 17,20(OH)₂D2. In placentas and Caco-2 cells, production of 20(OH)D2 was higher than 25(OH)D2 while in human keratinocytes the production of 20(OH)D2 and 25(OH)D2 were comparable. HaCaT keratinocytes showed high accumulation of 1,20(OH)₂D2 relative to 20(OH)D2 indicating substantial CYP27B1 activity. This is the first in vivo evidence for a novel pathway of vitamin D2 metabolism initiated by CYP11A1 and modified by CYP27B1, with the product profile showing tissue- and cell-type specificity.

  13. Formation of oxidizing species via irradiation of perchlorates using high-energy electrons and D 2 + ions

    NASA Astrophysics Data System (ADS)

    Crandall, Parker B.; Gillis-Davis, Jeffrey J.; Kaiser, Ralf-Ingo

    2016-10-01

    The perchlorate ion (ClO4-) has garnered particular interest in recent years following the discovery of perchlorate salts in the Martian regolith at levels of 0.4-0.6 wt% by the Phoenix lander in 2006 and Mars Science Laboratory's Curiosity rover in 2013. Due to their oxidizing properties, perchlorates are suspected to play a contributing role to the surprising lack of organics on the Martian surface. In this study, magnesium perchlorate hexahydrate (Mg(ClO4)2●6H2O) samples were irradiated with monoenergetic beams of 5 keV electrons and D2+ ions separately, sequentially, and simultaneously to simulate the effects of galactic cosmic ray exposure of perchlorates. The irradiation experiments were carried out under ultra-high vacuum conditions at 50 K, after which the samples were slowly heated to 300 K (0.5 K min-1) while desorbing products were monitored by quadrupole mass spectrometry. In all cases, molecular oxygen (O2) was detected upon the onset of irradiation and again during the warmup phase. In the case of simultaneous irradiation, deuterated water (D2O) and deuterium peroxide (D2O2) were also detected as the sample was heated whereas in the D2+ experiment small amounts of D2O2 was found exclusively. When samples were irradiated sequentially, the production of D2O2 was dependent upon the sample being irradiated with D2+ ions prior to electrons. These experiments show that perchlorates are capable of producing multiple oxidizing agents (O2, D2O2) which may also account for the lack of organics on the Martian surface.

  14. Imaging the high-affinity state of the dopamine D2 receptor in vivo: Fact or fiction?

    PubMed Central

    Skinbjerg, Mette; Sibley, David R.; Javitch, Jonathan A.; Abi-Dargham, Anissa

    2013-01-01

    Positron Emission Tomography (PET) has been used for more than three decades to image and quantify dopamine D2 receptors (D2R) in vivo with antagonist radioligands but in the recent years agonist radioligands have also been employed. In vitro competition studies have demonstrated that agonists bind to both a high and a low-affinity state of the D2Rs, of which the high affinity state reflects receptors that are coupled to G-proteins and the low-affinity state reflects receptors uncoupled from G-proteins. In contrast, antagonists bind with uniform affinity to the total pool of receptors. Results of these studies led to the proposal that D2Rs exist in high and low-affinity states for agonists in vivo and sparked the development and use of agonist radioligands for PET imaging with the primary purpose of measuring the proportion of receptors in the high-affinity (activating) state. Although several lines of research support the presence of high and low-affinity states of D2Rs and their detection by in vivo imaging paradigms, a growing body of controversial data has now called this into question. These include both in vivo and ex vivo studies of anesthesia effects, rodent models with increased proportions of high-affinity state D2Rs as well as the molecular evidence for stable receptor–G-protein complexes. In this commentary we review these data and discuss the evidence for the in vivo existence of D2Rs configured in high and low-affinity states and whether or not the high-affinity state of the D2R can, in fact, be imaged in vivo with agonist radioligands. PMID:21945484

  15. STS-55 MS3 Harris holds turbine blade sample at SL-D2 Rack 8 Werkstofflabor

    NASA Technical Reports Server (NTRS)

    1993-01-01

    STS-55 Mission Specialist 3 (MS3) Bernard A. Harris, Jr, wearing gloves, holds turbine blade sample and examines it in front of the Spacelab Deutsche 2 (SL-D2) Rack 8 Werkstofflabor (WL) (Material Sciences Laboratory). Harris is working at the Furnace for Turbine-blade geometry specimens to process special metallic alloys and cast them in the shape of turbine blades. SL-D2 is the German-managed payload aboard Columbia, Orbiter Vehicle (OV) 102.

  16. Evidence for limited D1 and D2 receptor coexpression and colocalization within the dorsal striatum of the neonatal mouse.

    PubMed

    Biezonski, Dominik K; Trifilieff, Pierre; Meszaros, Jozsef; Javitch, Jonathan A; Kellendonk, Christoph

    2015-06-01

    The striatum is the major input nucleus of the basal ganglia involved in reward processing, goal-directed behaviors, habit learning, and motor control. The striatum projects to the basal ganglia output nuclei via the "direct" and "indirect" pathways, which can be distinguished by their projection fields and their opposing effects on behavior. In adult animals, the functional opposition is modulated by the differential actions of D1 and D2 dopamine receptors (D1R, D2R), the expression of which is largely separated between these pathways. To determine whether a similar degree of separation exists earlier in development, we used dual-label immunohistochemistry to map dorsal-striatal D1R and D2R expression at the promoter level in postnatal day 0 (PD0) Drd1a-tdTomato/Drd2-GFP BAC transgenic mice, and at the receptor level by costaining for native D1R and D2R in wildtype (WT) PD0 animals. To assess for potential molecular interactions between D1R and D2R we also employed a recently developed proximity-ligation assay (PLA). Limited coexpression and colocalization of the D1R and D2R proteins was found in clusters of neurons endemic to the "patch" compartment as identified by costaining with tyrosine hydroxylase, but not outside these clusters. Moreover, in contrast to our recent findings where we failed to detect a D1R-D2R PLA signal in the adult striatum, in PD0 striatum we did identify a clear PLA signal for this pair of receptors. This colocalization at close proximity points to a possible role for D1R/D2R-mediated crosstalk in early striatal ontogeny.

  17. Striatal dopamine D(2) receptor availability in OCD with and without comorbid social anxiety disorder: preliminary findings.

    PubMed

    Schneier, Franklin R; Martinez, Diana; Abi-Dargham, Anissa; Zea-Ponce, Yolanda; Simpson, H Blair; Liebowitz, Michael R; Laruelle, Marc

    2008-01-01

    Dopamine D(2) receptor availability in the striatum has been reported to be low in generalized social anxiety disorder (GSAD) and obsessive-compulsive disorder (OCD), but it has not been studied in persons with comorbid OCD and GSAD (OCD+GSAD). D(2) receptor availability was assessed in 7 subjects with OCD+GSAD, 8 with OCD, and 7 matched healthy comparison (HC) subjects, all unmedicated adults. D(2) receptor availability was assessed with single-photon emission computerized tomography (SPECT) to measure binding potential (BP) of the D(2) receptor radiotracer [(123)I] iodobenzamide ([(123)I]IBZM). Mean striatal [(123)I]IBZM BP was significantly lower in the OCD+GSAD group (72.58 mL/g, SD=18.17) than in the HC group (118.41 mL/g, SD=45.40; P=.025). Mean BP in the OCD group (93.08 mL/g, SD=36.90) did not differ significantly from the HC group (P=.247). Trait detachment, as measured by the Detachment subscale of the Karolinska Scales of Personality, was negatively correlated with D(2) availability across all subjects (r(s)= -.55, P=.013). Comorbid GSAD and OCD may be associated with decreased availability of D(2) receptors in the striatum, consistent with prior findings in GSAD. Prior findings of decreased D(2) receptor availability in noncomorbid OCD were not confirmed. Decreased D(2) receptor availability was also associated with trait detachment, supporting prior findings in samples of healthy subjects.

  18. Bias Analyses of Preclinical and Clinical D2 Dopamine Ligands: Studies with Immediate and Complex Signaling Pathways

    PubMed Central

    Brust, Tarsis F.; Hayes, Michael P.; Roman, David L.; Burris, Kevin D.

    2015-01-01

    G protein–coupled receptors (GPCRs) often activate multiple signaling pathways, and ligands may evoke functional responses through individual pathways. These unique responses provide opportunities for biased or functionally selective ligands to preferentially modulate one signaling pathway over another. Studies with several GPCRs have suggested that selective activation of signaling pathways downstream of a GPCR may lead to safer and more effective drug therapies. The dopamine D2 receptor (D2R) is one of the main drug targets in the therapies for Parkinson’s disease and schizophrenia. Recent studies suggest that selective modulation of individual signaling pathways downstream of the D2R may lead to safer antipsychotic drugs. In the present study, immediate effectors of the D2R (i.e., Gαi/o, Gβγ, β-arrestin recruitment) and more complex signaling pathways (i.e., extracellular signal-regulated kinase phosphorylation, heterologous sensitization, and dynamic mass redistribution) were examined in response to a series of D2R ligands. This was accomplished using Chinese hamster ovary cells stably expressing the human D2L dopamine receptor in the PathHunter β-Arrestin GPCR Assay Platform. The use of a uniform cellular background was designed to eliminate potential confounds associated with cell-to-cell variability, including expression levels of receptor as well as other components of signal transduction, including G protein subunits. Several well characterized and clinically relevant D2R ligands were evaluated across each signaling pathway in this cellular model. The most commonly used methods to measure ligand bias were compared. Functional selectivity analyses were also used as tools to explore the relative contribution of immediate D2R effectors for the activation of more complex signaling pathways. PMID:25539635

  19. Behavioral sensitization to cocaine in rats: Evidence for temporal differences in dopamine D3 and D2 receptor sensitivity

    PubMed Central

    Collins, Gregory T.; Truong, Yen Nhu-Thi; Levant, Beth; Chen, Jianyong; Wang, Shaomeng; Woods, James H.

    2011-01-01

    Rationale Cocaine-induced changes in D2 receptors have been implicated in the expression of sensitized behavioral responses and addiction-like behaviors, however, the influence of D3 receptors is less clear. Objectives To characterize the effects of repeated cocaine administration on the sensitivity of rats to D2- and D3-mediated behaviors, as well as the binding properties of ventral striatal D2-like and D3 receptors. Methods Pramipexole was used to assess the sensitivity of rats to D3/D2 agonist-induced yawning, hypothermia, and locomotor activity, 24h, 72h, 10d, 21d and 42d after repeated cocaine or saline administration. The locomotor effects of cocaine (42d), and the binding properties of ventral striatal D2-like and D3 receptors (24h and 42d) were also evaluated. Results Cocaine-treated rats displayed an enhanced locomotor response to cocaine, as well as a progressive and persistent leftward/upward shift of the ascending limb (72h-42d), and leftward shift of the descending limb (42d) of the pramipexole-induced yawning dose-response curve. Cocaine treatment also decreased Bmax and Kd for D2-like receptors, and increased D3 receptor binding at 42d. Cocaine treatment did not change pramipexole-induced hypothermia or locomotor a